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A HISTORY OF HUMAN HELMINTHOLOGYDAVID I. GROVE MD. FRACP, FRCPA, DTM&H Department of Clinical Microbiology and Infectious Diseases The Queen Elizabeth Hospital Woodville South Australia C.A.B INTERNATIONAL C.A.B. International Wallingford Oxon OX10 8DE UK Tel: Wallingford (0491) 32111 Telex: 87964 (COMAGG G) Telecom Gold/Dialcom: 84: CAU001 Fax: (0491) 33508 ©C.A.B International 1900. All rights reserved. No part of this publication may be reproduced in any form or by any means, electronically, mechanically, by photocopying, recording or otherwise, without the prior permission of the copyright owners British Library Cataloguing in Publication Data Grove, David I A history of human helminthology 1. Man. helminthic diseases I. Title 616.962 ISBN 0-86198-689-7 Printed and bound in the UK by Bookcraft (Bath) Ltd CONTENTS Preface Acknowledgements 1. The nomenclature and classification of worms 2. Understanding the origin and transmission of worms 3. The discovery and development of anthelmintics 4. Fasciola hepatica and fascioliasis 5. Fasciolopsis buski and fasciolopsiasis 6. Clonorchis sinensis and clonorchiasis 7. Paragonimus westermani and paragonimiasis 8. Schistosoma haematobium and schistosomiasis haematobia 9. Schistosoma mansoni and schistosomiasis mansoni 10. Schistosoma japonicum and schistosomiasis japonica 11. Trematode infections of lesser importance 12. Echinococcus granulosus and echinococcosis or hydatid disease 13. Taenia solium and taeniasis solium and cysticercosis 14. Taenia saginata and taeniasis saginata 15. Diphyllobothrium latum and diphyllobothriasis 16. Cestode infections of lesser importance 17. Enterobius vermicularis and enterobiasis vii viii 1 33 75 103 127 141 159 187 233 263 297 319 355 385 397 421 439 Contents 18. Trichuris trichiura and trichuriasis 19. Ascaris lumbricoides and ascariasis 20. Anyclostoma duodenale, Necator americanus and hookworm disease 21. Strongyloides stercoralis and strongyloidiasis 22. Trichinella spiralis and trichinosis 23. Wuchereria bancrofti, Brugia species and filariasis 24. Loa loa and loiasis 25. Onchocerca volvulus and onchocerciasis 26. Dracunculus medinensis and Guinea worm disease 27. Nematode infections of lesser importance 28. Miscellanea 29. Biographies Person index Subject index 455 469 499 543 571 597 641 661 693 721 765 783 823 836 PREFACE In his History of Tropical Medicine published in 1939, HH Scott wrote : "Ankylostomiasis is almost the only helminthic infestation of man in the tropics which can be said to have a history, at all events a history of sufficient interest to call for any detail". Scott was wrong. Many worms a re visible to the naked eye and some have been recognized for millenia. The study of worms has been an integral component of Man's struggle to come to grips with the origin s of infectious diseases and the means by which they are transmitted from one to another. This book is an attempt to describe th e unfolding of those events which have led to our current understanding of helminth s infecting humans. They have occupied many centuries and have been undertaken b y diverse men and women in many locations and climes. The first three chapters of the book are gen eral in nature, the next eight are concerned with trematodes (flukes), the next five deal with cestodes (tapeworms and cysti c worms), the following eleven consider nematodes (roundworms) and the final chapter covers various miscellaneous items. Chapters concerned with specific worm infections follow a consistent plan, beginning with the discovery of the parasite and then its life cycle, followed by an historical treatment of how the clinical features have bee n recognized, diagnostic techniques developed, treatment evolved, the epidemiolog y understood and preventive and control measures applie d. Short biographies of the major research workers are appended at the end of the book. This work has been a labour of love from its conception some dozen years ago till the presentation of the typeset manuscript to the publisher. History is a dynamic subject, and it is my hope that others will build upon and refine all that is recounted herein. ACKNOWLEDGEMENTS I am very grateful to the University of Western Australia for twelve months' sabbatical leave during which time much of the basic research for this book was undertaken in the United Kingdom. Special tribute must be paid to two key sources. The first is th e magnificent Tropical Medicine and Parasitology: Classic Investigations edited by BH Kean, KE Mott and AJ Russell (Cornell University Press, Ithaca, 1978) in whic h translations of many of the most important original articles are brought together. The second is the Tropical Diseases Bulletin in which the helminthological literature has been abstracted since the early part o f this century. Thanks are due to Dr CR Morris for providing a photograph of his grandfather, WH Ransom, to Dr John Walker fo r obtaining a photograph of H Dew from the University of Sydney, and to Prof J Bailenger for assistance in collecting biographical details of L Normand and C Bavay. The photographic plates were expertly put together by Mr J Hadaway and Mr C Hentschke. Publication of these plates has been made possible by a generous grant from the Pathology Advisory Fund Committee of the Queen Elizabeth Hospital, Woodville, South Australia. This book has been produced on a personal computer using Wor d Perfect 5.1 (Word Perfect Corporation, Utah) and Glyphix (SWFTE International , Delaware). Finally, and most importantly, I must express my gratitude to my wife , Marilyn, and my children, Duncan, Graham, Br onwen and Lachlan, for the patience and forbearance they have shown during the many hours that this book has taken to prepare. Chapter 1 THE NOMENCLATURE AND CLASSIFICATIO N OF WORMS THE NATURE OF WORMS Worms are multicellular invertebrate animals, each of which belongs to one of several phyla or classes in the animal kingdom. The name "worm" is an in definite though emotive and evocative term which conjures up in the popula r mind visions of any elongated, creeping thing that is not obviously something else. This is not at all surprising, for the word, which is derived from the Latin "vermis", has been used down the centuries as an all-embracing description to apply to all worm-like creatures, whether they be earthworms, insect larvae in fruit, in vegetables or in trees, or parasitic worms in animals 34. Indeed, Linnaeus in the eighteenth century was even more liberal and used the titl e "Vermes" in his Systema Naturae to include a wide range of multicellula r organisms which we might now classify as invertebrates 32. Since worm-like creatures have been found in many branches of the animal kingdom, variou s authorities have drawn different lines of demarcation between worm an d non-worm. Worms are now, however, commonly considered to encompass the following phyla and classes: Nematoda (roundworms), Platyhelminthes (flat worms), Acanthocephala (thorny-headed worms), Nematomorpha (hairworms or gordiid worms) and Annelida (segmented worms including earthworms and leeches). These various groups differ from each other in both externa l appearance and fundamental organization, the sal ient features being summarized briefly as follows: (1) Nematoda The worms are elongated and cylindroidal in shape with a basically bilateral symmetrical arrangement. The integument consists of a non-nucleated cuticle secreted by the underlying hypodermis. They have a pseudocoele (a body cavity which is not lined with mesothelium), a complete gastrointestinal tract, and those that are parasitic in humans are unisexual. (2) Platyhelminthes These helminths are bilaterally symmetrical and are compressed dorsoventrally to give a leaf-like or tape-like shape. The integument generally consists of a syncitial cytoplasmic covering continuous with nucleated portions of the cytoplasm situated in the parenchyma beneath the muscle layer. They lack a body cavity, with the region between the internal organs being filled with spongy, mesenchymatous cells. Flatworms of human importance fall into two classes: a.Trematoda The worms are unsegmented and the adult forms are usually endowed with suckers and an incomplete gut (one aperture only). They may be either unisexual or 1 2 A History of Human Helminthology hermaphroditic. b. Cestoda The adult worms are usually segmented with the body being divided transversely into separate, sexually complete units called proglottids. The scolex (head) is provided with suckers + hooks. They have no gut and are hermaphroditic. (3) Acanthocephala The adult worms have a proboscis armed with hooks which is retractile into a sheath. The elongated, more or less cylindroidal worms have an integument that is perforated by canals, a large pseudocoele, no gastrointestinal tract and are unisexual. Transmission occurs through an arthropod intermediate host. (4) Nematomorpha These elongated, cylindroidal worms have a true body cavity, the mouth and anus is frequently absent, and the pharynx is degenerate. They have no excretory system and the sexes are separate. The adult forms are free-living in the soil while the juvenile stages are parasitic in arthropods. (5) Annelida These are bilaterally symmetrical, segmented creatures with a well-defined gut, body cavity and excretory, vascular and nervous systems. Earthworms (oligochaetes) and leeches (hirudines) are hermaphroditic, with the latter possessing suckers. The early physicians and naturalists, however, regarded parasitic worms a s an homogenous but separate an d discrete group of creatures without backbones that were characterized by the possession of a soft, elongated body without any locomotor appendage or well-developed hea d, and that were found in the bodies of other animals. In the early nineteenth century, Carl Rudolphi coined a ne w word, "Entozoa", to describe such organisms; this indicated that they wer e animals living inside the bodies of other animals 39. This word, which mean s literally "animal within" was derived from the Greek words (ENTOS) meaning "within" or "inside" and (ZOON) meaning "animal". This was a particularly useful term for parasitic worms and held sway while the concept that parasitic worms were a distinct systematic group persisted until the latter half of the nineteenth century. Eventually, however, with the discovery of th e complex life cycles and migrations of many worms, it became clear that th e word was inappropriate for describing the eggs and larvae of parasitic worms that might be found in the external environment. The word is rarely met wit h nowadays and worms are generally qualified as being either free-living o r parasitic worms or helminths. The latter word, "helminth", has much the same meaning in modern parlance as does "worm". It is derived from the Greek word, µ (HELMINS) [Combining form µ - (HELMINTHO-)] which was used by the ancient Greek physicians and naturalists to denote worms found in th e intestines of animals. "Helminthology", or the study of worms, is derived from a combination of µ (HELMINTHO-) and (LOGOS) meaning "account", "reason" or "discourse". Although the word may have no exac t meaning in zoological classification, it is common in medical terminology and is still used in the same sense as it was by Sir William Ramsay, physician t o King Charles II of England, in 1668. He published a volume entitle d Elminthologia, or some Physical Considerations of the Matter, Origination, Nomenclature and Classification 3 and Several Species of Worms Macerating and Direfully Cruciating every part of the Bodies of Mankind etc. which appears to be the first English textbook on this subject. In his book, Ramsay dealt with worms and their origin, thei r distribution within the human body, the effects of age and other factors o n susceptibility to infection, the clinical features, the prognosis, treatment an d methods of prevention of worm infections 35. Although used by some parasit ologists such Dujardin (Histoire naturelle des helminthes ou vers intestinaux , 184517) and Diesing (Systema Helminthum, 1849-1851 16), the term was not usually adopted in general pathological and medical texts until Requin (1852) in his "Élémens de pathologie médicale " argued that the term "la maladi e vermineuse" (wormy illness) was complex, clumsy and embarrassing, an d championed the use of the word "helminthiasis", derived from a combination of µ (HELMINTHIAN) meaning "to suffer from worms", and (ASIS), to denote "the condition of" suffering from a worm infection 38. There were, however, some opponents. Davaine (1877), for example, wrote that h e did not believe that medical language gained in clarity or conciseness by th e introduction of the expression 15. Nevertheless, the terms "helminth" an d "helminthiasis" found favour with many subsequent authors and are no w well-entrenched in the medical literature. AWARENESS OF PARASITIC WORMS DOWN THE AGES The Greek and Roman physicians of the M editerranean basin before and around the time of Christ recognized two, sometimes three, worms as parasitizing the human frame. All these worms were large and inhabited the gastrointestina l tract, hence they were appreciated relatively easily. Thus, Celsus (c.30 BC-38 AD)12 and Pliny (23-79 AD) 11 spoke of tapeworms and roundworms, whereas Hippocrates (c.460-374 BC) 22, Aristotle (384-c.322 BC) 4 and Galen (129-c.200 AD)19 were familiar with tapeworms ( Taenia species), round worms ( Ascaris lumbricoides) and threadworms (Enterobius vermicularis ). Ascaris lumbricoides was called in Greek µ (HELMINS STRONGYLE), meaning "round worm", Enterobius vermicularis was termed (ASKARIS, ASCARIS - there have been two transliterations, th e former said to be closer to the original etymologically and the latte r phonetically), and the tapeworm was known as µ (HELMINS PLATEIA) meaning "flatworm" or, more rarely, a s (TAINIA, TAENIA) meaning "band" or "ribbon worm". The Romans and those who wrote in Latin translated the word µ (HELMINS) by "lumbricus". They used this expression to encompass all th e intestinal worms, and also earthworms which they believed were closel y related. Thus, the word "lumbricus" was a group term analogous to a generi c description and was modified by an adjective to indicate the type in the fol lowing manner: "lumbricus teres" ("teres" = "round, cylindrical") for Ascaris 4 A History of Human Helminthology Table 1.1. Classification of worms infecting humans according to Linnaeus, 1758 33. (Worms found rarely or not then recognized as being pathogenic for humans have been omitted in Tables 1-14) ___________________________________________________________________ Classis Vermes CURRENT NAME Ordo Intestina Gordius medinensis Dracunculus medinensis Ascaris vermicularis Enterobius vermicularis Ascaris lumbricoides Ascaris lumbricoides Fasciola hepatica Fasciola hepatica Ordo Mollusca Ordo Testacea Ordo Lithophyta Ordo Zoophyta Taenia solium Taenia solium Taenia lata Diphyllobothrium latum ____________________________________________________________________ lumbricoides, "lumbricus latus" ("latus" = "broad, wide") for Taenia species, and "lumbricus terrenus" ("terrenus" = "earth") for the common earthworm. Following the fall of Rome in the fifth century AD, medical learning wa s largely maintained and developed throughout the Dark Ages by Persian an d Arabic physicians. These authors recognized three, four, or sometimes five , species of worms. They were all familiar with Ascaris lumbricoides and Enterobius vermicularis, but their understanding of tapeworms varied . Serapion (c. ninth century), for example, regarded the Taenia proglottids as distinct and independent worms which he called "cucurbitini" in view of their fancied resemblance to pumpkin seeds. He did not recognize Taenia itself as a worm but as a membrane formed by the intestine to hold and develop th e cucurbitini41. Avicenna (981-1037), in contrast, spoke of roundworms, threadworms, tapeworms and cucurbitini, with the last-named being considered as a distinct parasite 5. In addition, the Arabo-Persian physicians were familia r with dracunculiasis (Guinea worm infection) as a clinical entity, but th e verminous nature of the condition was a matter of debate amongst them (se e chapter 26). This was the situation which presented itself to the European physicians and naturalists of the Renaissance. The person who had the greatest and mos t profound influence on the nomenclature of helminths was the Swede, Carl von Linné (Carolus Linnaeus). This effect resulted, not from a prime consideration of helminths themselves, but as a consequence of his general treatment of al l living things. Following the classical line of thought, Linnaeus initially (1735) recognized three forms of worms as infecting humans: lumbrici (now known as Ascaris lumbricoides), ascarides (Enterobius vermicularis ) and taeniae (Taenia species and Diphyllobothrium latum )32. Linnaeus had divided th e animal world into six classes - Mammalia (mammals), Aves (birds), Amphibia Nomenclature and Classification 5 Table 1.2. Classification of worms infecting humans according to Goeze, 1782 21 ____________________________________________________________________ Genus CURRENT NAME Ascaris lumbricoides Ascaris lumbricoides Ascaris vermicularis cauda subulata Enterobius vermicularis Trichocephalos Trichuris trichiura Gordius Dracunculus medinensis Planaris latiuscula Fasciola hepatica Taenia cucurbitina grandis saginata Taenia saginata Taenia cucurbitina plana pellucida Taenia solium Taenia lata Diphyllobothrium latum Taenia visceralis socialis granulosa Echinococcus granulosus ____________________________________________________________________ (frogs etc.), Pisces (fish), Insecta (arthropods and crustaceans) and Verme s (other invertebrates). He then subdivided these classes into various orders, the Class Vermes being partitioned into five orders (Table 1.1). There wer e justifiable criticisms of his class ification. For example, George Louis Leclerc de Buffon, a wealthy French count and keeper of the Jardin du Roi, wrote wit h some acerbity that no-one could imagine that a mollusc was a worm or tha t crayfish were insects. With the publication of the tenth edition of his work i n 1758 33 , Linnaeus introduced a major change in the manner of describin g animals. He had derived his concepts of genus and species from Greek logic , and in the earlier editions of his Systema Naturae had used several lines o f descriptive text to define and differentiate various species. In this edition , however, he limited the species designation to a single word in order to reduce the expenses of publication. Thus, by a combination of force of circumstances and Greek logic, binary nomenc lature was born. By 1758, he acknowledged six species of worms, which were placed in two different orders, as being capable of infecting humans (Table 1.1). The differentiation between Taenia solium and Taenia lata (now known as Diphyllobothrium) was clearly established . Fasciola hepatica, which he had at one time regarded as a leech, now found its rightful place among the helminths, and Gordius medinensis (= Dracunculus medinensis) was becoming accepted increasingly by various authorities as being of a verminous nature. In 1782, the German pastor, Johann Goeze (Göze) published a major work on the natural history of worms inhabiting the bodies of animals entitle d Versuch einer Naturgeschichte der Eingeweidewürmer thierischer Körper 21. This book was written primarily for submission to the Royal Academy o f Science in Copenhagen which had set in 1780 a prize essay on the subject o f the origin of parasitic worms. Goeze argued for the spontaneous origin o f helminths and received second prize. His work, however, is a major contribution to the helminthological literature, particularly from a systematic point o f 6 A History of Human Helminthology Table 1.3. Classification of worms infecting humans according to Gmelin, 1788-1793 20 ____________________________________________________________________ Classis Vermes CURRENT NAME Ordo Intestina Ascaris vermicularis Enterobius vermicularis Ascaris lumbricoides Ascaris lumbricoides Trichocephalus hominis Trichuris trichiura Filaria medinensis Dracunculus medinensis Fasciola hominis Fasciola hepatica Taenia solium Taenia solium Taenia vulgaris Diphyllobothrium latum Taenia visceralis Echinococcus granulosus Taenia cellulosae Taenia solium ____________________________________________________________________ view. Goeze did not follow the binary system of nomenclature and often used a number of adjectives to describe each parasite. He divided worms into te n genera: Ascaris, Trichocephalos, Gordius, Cucullanus, Strongylus, Pseudoechinorhynchus, Planaria, Fasciola, Taenia and Chaos. He recognized nine species of worms as infecting the human body reasonably commonly (Tabl e 1.2). The additions to the worms described by Linnaeus were due to th e differentiation of Taenia saginata from T. solium by Goeze, his appreciatio n that hydatid cysts (Echinococcus granulosus ) were wormy in nature when he found the characteristic taeniid heads within each cyst, and the discovery in the interim by others of Trichuris, which Goeze renamed Trichocephalos when he found that what had been identified previously as the tail was in fact the head. Between 1788 and 1793, JF Gmelin issued a revised version of Linnaeus' s work which was published as the thirteenth edition of Systema Naturae 20. Gmelin retained the basic format used by Linnaeus. The total number o f parasitic species listed by Gmelin remained the same (Table 1.3), but th e number of species which are recognized today fell by one. Gmelin failed t o maintain Goeze's distinction between Taenia solium and Taenia saginata and this separation fell into oblivion for another 60 years. On the other hand, h e recognized correctly the helminthic nature of Cysticercus cellulosae , which he called Taenia cellulosae. He was completely unaware, however, that this organism was merely a stage in the life cycle of Taenia solium, and accorded it separate specific status. In 1798, G Cuvier in his Tableau élémentaire de l'histoire naturelle de s animaux, produced a classification which divided worms into two groups - the "cavitaires" and the "parenchymateux". Worms in the first group had a distinctive digestive cavity with an anus. The second group lacked complete digestive tubes: if there was a gut at all, it was incomplete with the anus being absent 14. In 1800, the German naturalist, Johann Zeder, published what was purport- Nomenclature and Classification 7 Table 1.4. Classification of worms infecting humans according to Zeder, 1800 43 and 180044 ____________________________________________________________________ Zeder, 1800 Zeder, 1803 CURRENT NAME Rundwürmer Rundwürmer Fusaria lumbricoides Fusaria lumbricoides Ascaris lumbricoides Fusaria dispar Mastigodes hominis Trichuris trichiura Fusaria vermicularis Enterobius vermicularis Filaria medinensis Dracunculus medinensis Hakenwürmer Hakenwürmer Saugwürmer Saugwürmer Distoma hepaticum Distoma hepaticum Distoma hepaticum Bandwürmer Bandwürmer Halysis solium Taenia solium Halysis lata Diphyllobothrium latum Blasenwürmer Blasenwürmer Polycephalus hominis Polycephalus echinococcus Echinococcus granulosus Cysticercus finna Taenia solium (also C. pyriformis, C. albopunctatus) ___________________________________________________________________ ed to be a revision of Goeze's work (Erster Nachtrag zur Naturgeschichte der Eingeweidewürmer mit Zusätzen und Anmerkungen herausgegeben von JGH Zeder), but was in fact so different as to be hardly recognizable as such 43. Not only did he revert to binary nomenclature and co mpletely change the generic and many of the specific names, but Zeder introduced a novel system of classifying worms which was the forerunner of the modern system of classification. H e divided the entozoa into five groups: Rundwürmer (roundworms) , Hakenwürmer (hookworms, equivalent to the modern Acanthocephala o r thorny-headed worms and not ancylostomes), Saugwürmer (sucking worms) , Bandwürmer (tapeworms) and Blasenwürmer (cystic worms) (Table 1.4). The Rundwürmer would become the modern nematodes and the Saugwürmer th e modern trematodes. The Bandwürmer and the Blasenwürmer would eventually be combined to form the cestodes, but this division by Zeder inhibite d realization that the two groups were related, and more than 50 years were t o pass before the relationship was proven with the recognition that cystic worms were intermediate stages in the life cycles of tape worms. Being a revision o f Goeze's work, this edition was n ot all-encompassing and a number of important human pathogens were omitted. In 1803, Zeder produced a new book entitled Anleitung zur Naturgeschichte der Eingeweidewürmer 44. He again used the same classification as he ha d employed three years earlier. Although he generally gave the worms different names, he recognized the same species as infecting humans as di d 8 A History of Human Helminthology Table 1.5. Classification of worms infecting humans according to Rudolphi. 1808-1810 39 ____________________________________________________________________ Ordo Nematoideorum CURRENT NAME Filaria medinensis Dracunculus medinensis Trichocephalus dispar Trichuris trichiura Ascaris lumbricoides Ascaris lumbricoides Ascaris vermicularis Enterobius vermicularis Ordo Trematodorum Distoma hepaticum Fasciola hepatica Ordo Cestoideorum Taenia lata Diphyllobothrium latum Taenia solium Taenia solium Ordo Cysticorum Cysticercus cellulosae Taenia solium Echinococcus hominis Echinococcus granulosus (also E. simiae E. veterinorum) ___________________________________________________________________ Gmelin (Table 1.4). He divided (incorrectly) Gmelin's Taenia cellulosae into three species and placed them in a new genus named Cysticercus. The worm infecting humans he called C. finna, that infecting subhuman primates he designated C. pyriformis, and that infecting other animals he labelled C. albopunctatus. Between 1808 and 1810, the German physician, Carl Rudolphi published a massive opus totalling 1,370 pages entitled Entozoorum, sive vermium intestinalium historia naturalis meaning the natural history of entozoa or intestinal worms 39 . He took the same basic five groups as proposed by Zeder and con verted the German names into classical ones. It was from these names that the modern words nematode, trematode and cestode are derived. (1) The roundworms became t he Entozoa Nematoidea. This name was derived from a combination of the Greek words µ (NEMA) [combining for m µ - (NEMATO)] = "thread" and (ODES) = "like, of the nature of", to indicate their filiform or thread-like sh ape. He defined them as being "corpore elongato, cylindrico, tenuissime, an ulato, elastico" 39meaning that the body of the worm was elongated, cylindrical, thin, ringed and elastic. (2) the "hookworms" became the Entozoa Acanthocephala. This name was derived from a combination of the Greek words (AKANTHA, ACANTHA) = "spine" or "thorn" and (KEPHALE, CEPHALE) = "head", to indicate the characteristic hooks on the head of the worms. H e defined them as being "corpore teretiusculo, utriculari, subelastico, proboscide seriatim uncinata, retractili" 39 meaning that the body was slightly rounded , bag-shaped and partly elastic, while the probosc is or head had a row of retractile hooks. (3) The sucking worms became the Entozoa Trematoda. This name was de- Nomenclature and Classification 9 Table 1.6. Classification of worms infecting humans according to Bremser, 1819 10 ____________________________________________________________________ Nematodeorum CURRENT NAME Ascaris lumbricoides Ascaris lumbricoides Oxyuris vermicularis Enterobius vermicularis Trichocephalus dispar Trichuris trichiura Filaria dracunculus Dracunculus medinensis Trematodorum Distoma hepaticum Fasciola hepatica Cestoideorum Taenia solium Taenia solium Bothriocephalus latus Diphyllobothrium latum Cysticorum Cysticercus cellulosae Taenia solium Echinococcus hominis Echinococcus granulosus (also E. veterinorum) ____________________________________________________________________ rived from the Greek word µ (TREMATODES) meanin g "foraminous" or "pierced with holes", to reflect the fact that they were usually provided with conspicuous suckers ( µ is a combination of µ = "hole" or "orifice" and (ODES) = "of the nature of"). Rudolphi defined them as being "corpore depresso vel teretiusculo, molli, poris suctoriis" 39 meaning that the body was flattened or slightly rounded, soft and provided with sucking holes. (4) The tapeworms became the Entozoa Cestoidea. This name was derive d from a combination of the Gre ek words (KESTOS, CESTOS) = "tape", "belt" or "ribbon" and (ODES) = "of the nature of", to indicate that they are elongated, ribbon-like organisms. He defined them as being "corpor e elongata, depresso, molli"39 meaning that the body was elongated, flattened and soft. (5) The cystic worms became the Ento zoa Cystica. This name was derived from the Greek word (KUSTIS, CYSTIS) meaning "bladder". He define d them as being "membranacei, plerumque rugosi, intus cavi, capitis coron a uncinata, cystide inclusi" 39 meaning that they had a generally wrinkle d membrane and an internal cavity containing heads crowned with hooks. The species of worms that Rudolphi recognized as being of huma n importance are indicated in Table 1.5. It can be seen that there were n o significant changes from those published by Zeder. Rudolphi gave the generic name of Echinococcus to hydatids and divided them (incorrectly) into thre e species, hominis, simiae, and veterinorum to reflect their location in human , subhuman primate, and domestic or other animal hosts. In 1819, Rudolphi produced a revision of his opus entitled Entozoorum Synopsis 40. He listed a total of 993 species of parasitic worms, 552 of whic h he considered as definite and 441 as being dubious. There were no majo r 10 A History of Human Helminthology Table 1.7. Classification of worms infecting humans according to Dujardin, 1845 17 ____________________________________________________________________ Nématoides CURRENT NAME Trichocephalus dispar Trichuris trichiura Filaria medinensis Dracunculus medinensis Filaria oculi humani Loa loa (also F. lacrymalis) Oxyuris vermicularis Ascaris lumbricoides Trichina spiralis Trichinella spiralis Trématodes Distoma hepaticum Fasciola hepatica Cestoïdes (Cestoidea et Cystica of Rudolphi) Taenia solium Taenia solium Bothriocephalus latus Diphyllobothrium latum Cysticercus cellulosae Taenia solium Echinococcus veterinorum Echinococcus granulosus ____________________________________________________________________ changes to the parasites infecting humans in this volume, other than hi s acceptance of the separation by Bremser of Diphyllobothrium latum from the genus Taenia and his placement of it in the genus Bothriocephalus. In the same year (1819), JG Bremser, custodian of the Imperial museum in Vienna published his book entitled Ueber lebende Würmer im lebende n Menschen 10. No new worms of human importance were listed (Table 1.6), but he transferred Ascaris vermicularis to the genus Oxyuris and, as mentioned, reclassified Taenia lata as Bothriocephalus latus. He recognized two species of Echinococcus, E. hominis and E. veterinorum in other animals. In 1845, the Frenchman Felix Dujardin produced his Histoire naturelle des helminthes ou vers intestinaux 17. His classification had features of bot h Rudolphi's and Cuvier's systems. He divided the parasitic worms into two basic groups which were in turn partitioned into subclasses. The animals of the first group had a gut. This category was then subdiv ided depending upon whether the gut was complete or incomplete, and whether the worms were unisexual o r hermaphroditic. Unisexual worms with a complete gut but no spines on th e proboscis were placed in the subclass Nématoï des, while those with spines were located in the subclass Acanthothèques. Hermaphroditic worms with a n incomplete gut were in the subclass Trématodes. The second group had n o intestines or true mouth and were in turn partitioned. Those with separate sexes were placed in the subclass Acanthocéphales, while those which wer e hermaphroditic were set in the subclass C estoïdes. This last group encompassed both the Cestoidea and Cystica of Rudolphi. Two major additions to huma n helminths were listed (Table 1.7). Trichina spiralis was described in detail, and the worm now known as Loa loa was mentioned and stated as being definitely different from Dracunculus medinensis , although no details were provided. Nomenclature and Classification 11 Table 1.8. Classification of worms infecting humans according to Diesing, 1849-1851 16 ____________________________________________________________________ Nematoidea CURRENT NAME Trichina spiralis Trichinella spiralis (also T. affinis) Ascaris vermicularis Enterobius vermicularis Ascaris lumbricoides Ascaris lumbricoides Filaria medinensis Dracunculus medinensis Trichocephalus dispar Trichuris trichiura Ankylostomum duodenale Ancylostoma duodenale Trematoda Distoma hepaticum Fasciola hepatica Cephalocotylea Echinococcus polymorphus Echinococcus granulosus Cysticercus cellulosae Taenia solium Taenia solium Taenia solium Dibothrium latum Diphyllobothrium latum ____________________________________________________________________ Soon afterwards, in 1849 and 1851, the German CM Diesing issued his two volume Systema Helminthum totalling 1,267 pages16. Human helminths fell into three orders, the Nematoidea, Myzelmintha and Cephalocotylea. The orde r Myzelmintha included two suborders, the Cercariaea and Trematoda. Th e Cercariaea contained many species of the genera Cercaria of Müller and Redia of de Filippi which were later shown to be larval stages of adult worms placed in the suborder Trematoda. In this book, another species of human importance, Anchylostomum duodenale , was now listed (Table 1.8). The labours of Goeze, Zeder, Rudolphi, Dujardin, Diesing and others ha d expanded helminthology greatly, developing it into a specialized study of th e metazoan parasites of the internal organs and structures of Man and animals. In the process, however, the relationship between these worms and non-parasitic animals was largely lost, for the parasitic helminths were generally considered to be a separate and peculiar class of animals. There were opponents of thi s view, such as CE von Baer and FS Leuckart, but this error was not correcte d finally until the middle of the nineteenth century when Carl Vogt united th e various groups of parasitic helminths with those of the free-living animals with which they were closely relate d42. Thus, Vogt classified the parasitic nematodes together with the free-living nematodes in the Nemathelminthes, and cas t parasitic cestodes and trematodes with free-living flatworms such a s turbellarians in the Platyhelminthes. While this was satisfying for the zoologist, it was not particularly relevant to the medical practitioner who was less interested in systematics and preferred to consider the helminths as a biological group. With the appearance in 1855 of Friedrich Küchenmeister's book Die in und an dem Körper des lebende n Menschen vorkommenden Parasiten 28, medical helminthology leaves th e 1864 13 ____________________________________________________________________ Nematoda CURRENT NAME Ascaris lumbricoides Ascaris lumbricoides Trichocephalus dispar Trichuris trichiura Trichina spiralis Trichinella spiralis Sclerostoma duodenale Ancylostoma duodenale Oxyuris vermicularis Enterobius vermicularis Dracunculus medinensis Dracunculus medinensis Dracunculus loa Loa loa Trematoda Fasciola hepatica Fasciola hepatica Bilharzia haematobia Schistosoma haematobium Cestoda Taenia solium Taenia solium Taenia mediocanellata Taenia saginata Taenia flavopunctata Hymenolepis diminuta Taenia nana Hymenolepis nana Taenia elliptica Dipylidium caninum Taenia echinococcus Echinococcus granulosus Bothriocephalus latus Diphyllobothrium latum ____________________________________________________________________ .10.12 A History of Human Helminthology Table 1. Classification of worms infecting humans according to Küchenmeister.9. Classification of worms infecting humans according to Cobbold. 185528 ____________________________________________________________________ Nematelmia CURRENT NAME Trichocephalus dispar Trichuris trichiura Trichina spiralis Trichinella spiralis Oxyuris vermicularis Enterobius vermicularis Ancylostoma duodenale Ancylostoma duodenale Ascaris lumbricoides Ascaris lumbricoides Filaria medinensis Dracunculus medinensis Trematodea Distoma hepaticum Fasciola hepatica Distoma haematobium Schistosoma haematobium Cestoidea Bothriocephalus latus Diphyllobothrium latum Taenia solium Taenia solium Taenia mediocanellata Taenia saginata Taenia nana Hymenolepis nana Echinococcus altricipariens Echinocococcus granulosus Echinococcus scolicipariens Echincococcus granulosus ____________________________________________________________________ Table 1. Similarly. saginata. Classification of worms infecting humans according to Davaine. culminated in the disappearance of these genera from the list of flatworms as promulgated by Dujardin an d Diesing. He blotted his copybook a little.11. altricipariens. however. von Siebold and others (see chapters 2.9 .Nomenclature and Classification 13 Table 1. a series of texts appeared which were devoted primarily or exclusively to human helminthology.4). Schistosoma haematobium and the common but relatively innocuous Hymenolepis nana had been discovered by Bilharz. 13). 12. by making a false subdivision of Echinococcus granulosus into E. The publication by Steenstrup in 1842 of the Alternation of Generations in which he showed that cercariae and rediae were merely stages in th e reproduction of trematodes (see chapters 2. The worms discussed by Küchenmeister are listed in Table 1. eliminated bladderworms such as Cysticercus cellulosae as separate species. The major addition by the time of Cobbold's book in 1864 13 was acceptance of Loa loa as a distinct nematode that was not uncommon in certain parts o f . and Küchenmeister himself had rediscovered the difference between Taenia solium and T. Several major advances had occurred by then. 1877 15 ____________________________________________________________________ Nématodes CURRENT NAME Oxyuris vermicularis Enterobius vermicularis Ascaris lumbricoides Ascaris lumbricoides Trichocephalus dispar Trichuris trichiura Anchylostoma duodenale Ancylostoma duodenale Anguillula stercoralis Strongyloides stercoralis Anguillula intestinalis Strongyloides stercoralis Trichina spiralis Trichinella spiralis Filaria medinensis Dracunculus medinensis Filaria sanguinis hominis Wuchereria bancrofti Trématodes Distomum hepaticum Fasciola hepatica Distomum crassum Fasciolopsis buski Distomum haematobium Schistosoma haematobium Cestoïdes Taenia solium Taenia solium Taenia mediocanellata Taenia saginata Taenia nana Hymenolepis nana Taenia flavopunctata Hymenolepis flavopunctata Tania echinococcus Echinococcus granulosus Bothriocephalus latus Diphyllobothrium latum ____________________________________________________________________ major works of systematic helminthology. From Küchenmeister's time. scolicipariens and E. the demonstration of the relationship between cystic worms and tapeworms by Küchenmeister. Perhaps most importantly of all. new understandings of the transmission of worms had led to alterations in the manner of classification. 14 A History of Human Helminthology Table 1. hence their designation as Filaria hominis sanguinis . and they were each given separate specific s tatus. but it was not at first realized that the parasitic female worm and th e first-stage larva were different stages in the life cycle of the same parasite.11). but the finding of further cases in th e 1870's renewed interest in a previously obscure parasite. Although the adult worm had be en discovered in 1876 by Bancroft. Microfilariae had been discovered a number of years earlier by Demarquay then had been identified in the blood by Lewis in 1872. In addition. Classification of worms infecting humans according to Blanchard. 1885-18908 ____________________________________________________________________ Nematodes CURRENT NAME Ascaris lumbricoides Ascaris lumbricoides Oxyuris vermicularis Enterobius vermicularis Trichocephalus dispar Trichuris trichiura Ankylostoma duodenale Ancylostoma duodenale Rhabdonema intestinale Strongyloides stercoralis Filaria loa Loa loa Filaria medinensis Dracunculus medinensis Filaria sanguinis hominis Wuchereria bancrofti Trematodes Distoma hepaticum Fasciola hepatica Distoma sinense Clonorchis sinensis Distoma japonicum Clonorchis sinensis Distoma buski Fasciolopsis buski Distoma ringeri Paragonimus westermani Distoma heterophyes Heterophyes heterophyes Bilharzia haematobia Schistosoma haematobium Cestodes Taenia saginata Taenia saginata Taenia solium Taenia solium Taenia echinococcus Echinococcus granulosus Taenia nana Hymenolepis nana Taenia canina Dipylidium caninum Bothriocephalus latus Diphyllobothrium latum ____________________________________________________________________ the world (Table 1.10). Strongyloides stercoralis was discovered in the pre-ceding year. news of the find came too late to be incorporated into Davaine's book and his descriptio n was based upon the microfilaria l stage.12. By the appearance of Blanchard's two volume work in 1885-1890 8. Two new nematodes and another trematode made their appearance in Davaine's text i n 187715 (Table 1. stercoralis had been determined an d . the parasites now known as Hymenolepis diminuta and Dipylidium caninum were listed as infecting humans. the identity of Anguillula intestinalis and A. Fasciolopsis buski had been discovered more than forty years before by Busk. 12). and Stiles had diff erentiated Necator americanus from Ancylostoma duodenale . major fin ds had been made with the trematodes. In addition. Katsur- . By 1906. 1906 ___________________________________________________________________ Nematoda CURRENT NAME Strongyloides intestinalis Strongyloides stercoralis Filaria medinensis Dracunculus medinensis Filaria bancrofti Wuchereria bancrofti Filaria diurna Loa loa Filaria perstans Mansonella perstans Filaria ozzardi Mansonella ozzardi Filaria loa Loa loa Filaria volvulus Onchocerca volvulus Trichocephalus trichiurus Trichuris trichiura Trichinella spiralis Trichinella spiralis Ankylostoma duodenale Ancylostoma duodenale Uncinaria americana Necator americanus Ascaris lumbricoides Ascaris lumbricoides Oxyuris vermicularis Enterobius vermicularis Trematoda Fasciola hepatica Fasciola hepatica Fasciolopsis buski Fasciolopsis buski Paragonimus westermani Paragonimus westermani Opisthorchis felineus Opisthorchis felineus Opisthorchis sinensis Clonorchis sinensis Schistosomum haematobium Schistosoma haematobium Schistosomum japonicum Schistosoma japonicum Cestoda Dibothriocephalus latus Diphyllobothrium latum Dipylidium caninum Diphylidium caninum Hymenolepis nana Hymenolepis nana Hymenolepis diminuta Hymenolepis diminuta Taenia solium Taenia solium Taenia saginata Taenia saginata Taenia echinococcus Echinococcus granulosus Echinococcus multilocularis Echinococcus multilocularis _________________________________________________________________________ Blanchard called the parasite Rhabdonema intestinale (Table 1. updated by Sambon and Theobald. Mention was also made of the parasite now called Heterophyes heterophyes . Baelz had incorrectly divided the former parasite into two species and Blan chard perpetuated the error. several new nematodes had been described (Table 1. Filaria ozzardi and Filaria perstans had been discovered. Two new flukes of some importance had been discovered . Classification of worms infecting humans according to Braun. when the English version of Braun's textbook was published 9. two new filarial parasites.Clonorchis sinensis by McConnell and Paragonimus westermani in humans by Ringer and Manson . Similarly.13). Manson had reported in 1893 a portion of Leuckart's description of Onchocerca volvulus from specimens sent to him from West Africa by a missionary.13.Nomenclature and Classification 15 Table 1. The second edition of Faust's text on human helminthology 18 in 1939 incorporated two major changes (Table 1. and Lichtenstein and Brug had appreciated tha t certain microfilariae in Southeast Asia were different from those of Wuchereria bancrofti and these had been labelled microfilaria malayi. Brugia timori and Schistosoma mekongi would be discovered or differentiated in the next few decades. a number of authors wer e beginning to accept the specificity of Echinococcus multilocularis .15 lists those worms which have been des cribed in Beaver. Jung and Cupp's 1984 revision of Craig and Faust's Clinical Parasitology as infecting humans 6. This led to chaos and confusion and inhibited the flow of ideas and the generation of new discoveries.14). Furthermore.14. to extremely rare ones which have been encountered in humans onl y once or twice. 1939 18 ____________________________________________________________________ Nematodes Trematodes Cestodes Trichinella spiralis Schistosoma haematobium Diphyllobothrium latum Trichocephalus trichiurus Schistosoma mansoni Hymenolepis nana Strongyloides stercoralis Schistosoma japonicum Hymenolepis diminuta Ancylostoma duodenale Fasciola hepatica Dipylidum caninum Necator americanus Fasciolopsis buski Taenia solium Enterobius vermicularis Opisthorchis species Taenia saginata Ascaris lumbricoides Clonorchis sinensis Echinococcus granulosus Wuchereria bancrofti Paragonimus westermani Onchocerca volvulus Acanthocheilonema perstans Mansonella ozzardi Loa loa Dracunculus medinensis microfilaria malayi _________________________________________________________________________ ada had discovered Schistosoma japonicum in 1904 and Opisthorchis felineus was now appreciated as infecting humans. Classification of worms according to Faust. for unles s everyone possessed a common language. Finally. infections with Opisthorchis viverrini had been recognized. such as Ascaris lumbricoides which infects nearly one billion people. These represented the last major discoveries of worms important for human medicine althoug h worms of limited geographical distribution such as Capillaria philippinensis . THE RULES OF ZOOLOGICAL NOMENCLATURE It is clear from the foregoing discussion that many different names were often used to describe the same worm. These parasites range from exceedingl y common worms. Table 1.16 A History of Human Helminthology Table 1. there was considerable uncertainty . The specific systematic position of Schistosoma mansoni proposed in 1908 by Sambon had been proven b y transmission experiments. This problem applied not just to medical helminthology. Jung and Cupp. Raphae l Blanchard.15. but was even more germane to zoologists who had to deal with more than a million animal species. Classification of worms according to Beaver. The Third Congress in 189 5 appointed an international commission to develop a code which would be ac- . the Frenchman. ____________________________________________________________________ Class Nematoda Ancylostoma ceylanicum Ancylostoma duodenale* Angiostrongylus species Anisakis species Ascaris lumbricoides* Brugia malayi* Brugia timori multilocularis Capillaria species Dioctophyma renale Dirofilaria species Dracunculus medinensis* madagascariensis Enterobius vermicularis* Gnathostoma spinigerum Gongylonema pulchrum Haemonchus contortus Lagochilascaris minor Loa loa* Mammomonogamus laryngeus Mansonella ozzardi Mansonella perstans Mansonella streptocerca Metastrongylus elongatus Necator americanus* Phocanema species Oesophagostomum species Onchocerca volvulus* Phocanema species Physaloptera caucasica Strongyloides fülleborni Strongyloides stercoralis* Ternidens deminutus Thelazia species Toxocara species Trichinella spiralis* Trichuris trichiura* Wuchereria bancrofti* * common or relatively common Class Trematoda Achillurbania species Alaria species Clonorchis sinensis* Dicrocoelium dendriticum Echinostoma species Fasciola gigantica Fasciola hepatica Fasciolopsis buski Gastrodiscoides hominis Heterophyes heterophyes Metagonimus yokogawai Opisthorchis felineus Opisthorchis viverrini Paragonimus westermani* Plagiorchis species Poikilorchis species Schistosoma haematobium* Schistosoma intercalatum Schistosoma japonicum* Schistosoma mansoni* Schistosoma margrebowiei Schistosoma mattheei Schistosoma rodhaini Spelotrema species Troglotrema salmincola Watsonius watsoni Class Cestoidea Bertiella species Diphyllobothrium cordatum Diphyllobothrium latum* Diplogonoporus grandis Dipylidium caninum Echinococcusgranulosus* Echinococcus Echinococcus vogeli Hymenolepis diminuta Hymenolepis nana* Inermicapsifer Mesocestoides variabilis Raillietina demerariensis Sparganum species Spirometra houghtoni Taenia brauni Taenia multiceps Taenia saginata* Taenia serialis Taenia solium* Taenia taeniaeformis ____________________________________________________________________ as to what other writers were saying. presented a Code to the First International Zoological Congress in Paris in 1889. In an attempt to produce uniformity and order. This code was adopted by that and the subsequent Congress in 1892 but failed to receive universal support. 1984 6.Nomenclature and Classification 17 Table 1. e. the International Code of Zoological Nomenclature was p resented and the commission was made permanent. notice of at least one year had to b e given in two or more of the following publications: Bulletin de la Société Zoologique de France. In addition to these articles. where the same name has been applied to two o r more different animals. The 36 basic articles which were adopted ar e reproduced in Table 1.18 A History of Human Helminthology ceptable to all zoologists. particularly in the medical sphere. This is an example where a name is a homonym. Monitore Zoologica. An example of the former is the differentiation of the Taenia solium and Taenia saginata. but the article which gave rise to the greatest dissent and concern. Progress reports were delivered at the Fourth (1898) and Fifth (1901) Congresses. Furthermore. definition or description of the organism . provided the principles of binary nomenclature were followed and the nam e was accompanied by an indication. The accumulation of knowledge over the years has in many instances necessitated the splitting of a species or the subdivision of a genus. In such cases. Trichina spiralis of Owen 1835 was changed to Trichinella spiralis by Railliet in 1895 when it was realized that the generic name had already b een used for an insect. If the vote of the commission was no t unanimous. Science.16. The naming of animals was based upon the binary system o f nomenclature. a name has been applied which had already been used fo r another member of the animal kingdom. the genus Distoma of Retzius 1790 has been subdivided into man y genera including Clonorchis. All these eventualities were covered in the rules. then the matter would be referred to the next Internationa l Congress which would appoint a special boar d of three members to make a final decision. At the Sixth Congress in 1904. On some occasions. Paragonimus and Schistosoma. Article 26 provided the foundation stone upon which the whole edifice was erected for this statement confirmed that the starting point for such an arrangement began with the publication in 1758 of the tenth edition o f Linnaeus's Systema Naturae. Fasciolopsis. or Zoologischer Anzeiger in order to allow debate. a procedure was devised whereby the rules could be suspended in certai n cases. . The code consisted of 36 articles supplemented with various recommend ations including a code of ethics and conditions for the suspension of the rules in certain cases. Nature. Thus. a code of ethics was laid down in which it wa s suggested that when an author published a name of a new genus or specie s which was preoccupied. This contra sts with synonyms which are different names used for the same animal. i. the person discovering the error should inform th e author and give him ample opportunity to propose a new name. was Article 25 which described the law of priority. The circumstance in which this could arise would be when the com mission judged that a strict application of the rules would result in greate r confusion than uniformity. This law required that the valid name of a genus or species was the name under which it was first described . In like manner. Article 14 . galliae.While specific substantive names derived from names of persons may be writte n with a capital initial letter. If. bosi (not bovis).16. Corvus corax. mohammed. sturionis. the name of the typical subgenus must be the same as the name of the genus (see Article 25). i "Article 10 . Oestrus ovis. the genitive is always formed by adding. salmoni (not salmonis). when the genus so named becomes a subgenus and vice versa "Article 8 . or of compound words indicating a comparison with a simple object. Laophonte Mohammed or L. cedo-nulli or cedonulli. "Article 5 . victoris. "Article 2. Ceratodus.The name of a family is formed by adding the endingidae. or considered and treated as such in case they are not of classic origin. and employed as a substantive in the nominative singular. . . to the exact and complete name. Examples: cuvieri. even if the name has a Latin form. antonii.Nomenclature and Classification 19 Table 1. Hypoderma Diana or H. this name is to be placed n parenthesis between the generic and the specific names. written with a capital initial letter. that is. antilarum. .The scientific designation of animals is uninominal for subgenera and all highe r groups. "Article 12 . "Article 7 . . that is. In these cases the two words composing the specific name are written as one word with or without the hypen . however. they are of the same value.Specific names are: "(a) Adjectives. aristotelis. which must agree grammatically with the generic name. Francolinus Lucani or F. merianae. Example:Felis leo. an organism is transferred from the vegetable to the animal kingdom its botanica l names are to be accepted in zoological nomenclature with their original botanical status. all other specific names are to be written with a small initial letter . jan-mayeni or janmayeni. binominal for species. "Article 13 .The name of a family or subfamily is to be changed when the name of its type genus is changed. the genitive s i formed in accordance with the rules of Latin declination in case the name was employed an d declined in Latin. they are of the same value. "Article 15 . diana. elisabethae. petri (given name). "If the name is a modern patronymic. Article 11 . simple or compound. "Article 9 . the name of a subfamily by adding inae. "Article 6 . does not form an exception to Article 2. "If the name is given as a dedication to one or several persons.When it is desired to cite the name of a subgenus. and from a nomenclatural standpoint they are coordinate. sanctae-helenae. and if an organism is transferred from the animal to the vegetable kingdom its names retain their zoological status. cuvieri. Example: sanctae-catharinae or sanctaecatharinae.Generic and subgeneric names are subject to the same rules and recommendations. nuñezi. "Article 3. to the root of the name of its type genus. sarasinorum. it is placed in the plural if the dedication involves several persons of the same name. sancti-pauli. "Article 4 . and vice versa. Examples: plini. Example: Felis marmorata. an i if the person is a man. "(c) Substantives in the genitive. Examples:Vanessa (Pyrameis) cardui.A generic name must consist of a single word. lucani. Examples: Rhizostoma Cuvieri or R. or an ae if the person is a woman. and trinominal for subspecies.Specific and subspecific names are subject to the same rules and recommendations. cor-angium or coranguinum. möbiusi.A specific name becomes a subspecific name when the species so named becomes a subspecies. and from a nomenclatural standpoint they are coordinate. Perca.If a genus is divided into subgenera. The rules of zoological nomenclature (cited in 18) ____________________________________________________________________ "Article 1. Hymenolepis.A generic name becomes a subgeneric name. Examples:Canis. Examples: rosae.The scientific names of animals must be words which are either Latin or Latinized.Zoological nomenclature is independent of botanical nomenclature in the sense that the name of an animal is not to be rejected simply because it is identical with the name of a plant.The use of compound proper names indicating dedication. cornu-pastoris or cornu-pastoris. "(b) Substantives in the nominative in apposition with the generic name. the name of the author of the specific name is retained in the notation but placed in parentheses. but the generic name is preceded by the sign of multiplication. Examples: Primates Linné. without the interposition of any mark of punctuation. spitzbergensis.When a species is transferred to another than the original genus or the specific name is combined with any other generic name than that which it was originally published. 1758). such is written immediately following the specific name. 1826. or Primates Linné (1758). or a typographical error is evident. sanctae-helenae. Mülleria. f "Article 19 .20 A History of Human Helminthology Expressions like rudis palnusque are not admissible as specific names. "Article 25 . Lamarckia. the same asif it were a true species. medi i. ora description. "Article 20 . Krøyeria. "Article 23 . patagonicus.The notation of hybrids may be given in several ways. the restricted species to which the original specific name of the primitive species is attributed may receive a notation indicating both the name of the original author and the name of the reviser. Example: Capra hircus/Ovis aries. "(c) The fractional form is also preferable in case one of the parents is itself a hybrid. diemensis. Köllikeria. "Article 21 . Example: Bernicla canadensis/Anser cygnoides Rabé.The tenth edition of Linné's Systema Naturae. and Distoma hepaticum (Linné.. including diacritic marks. o r description. in all cases the name of the male parent precedes that of the female parent. as if it were not a hybrid. "Article 22 . emend. the hybrid take s provisionally a specific name. is to be retained. sp n. Article 18 .When a species is divided.). Example: X Coregonus dolosus Fatio. In the latter case. and "(b) That the author has applied the principles of binary nomenclature. etc. a definition or a description unless it is clear from the contents of the publication that some other person is responsible for said name and its indication. edwardiensis.. faröensis.The original orthography of a name is to be preserved unless an error o transcription. or a definition.The author of a scientific name is that person who first publishes the name n i connection with an indication. parenthesis may b e used. Examples: sancti-pauli. Examples: Selysius. Hallowell. Example: (Tetrao tetrix X Tetrao urogallus) X Gallus gallus. vindobonensis. 1820) Moquin-Tandon. This second method is in so far preferable that it permits the citation of the person who first published the hybrid form as such. Example : Taenia lata Linné. the male parent forming the numerator and the female parent the denominator. "(b) Hybrids may also be cited in form of a fraction. but are separated from it bya comma or by parentheses. Example:Rana esculenta marmorata Hallowell.The valid name of a genus or species can be only that name under which it was first designated on the condition: "(a) That this name was published and accompanied by an indication. Stilia. Article 17 .In forming names derived from languages in which the Latin alphabet is used. 1758). but not Rana esculenta (marmorata) or Rana marmorata. paraguayensis. Fasciola hepatica Linné.If it is desired to cite the author's name. or are to b placed in the adjectival form. möbiusi. if other citations are desirable (date.. "Article 24 . 1758. Example: Taenia solium Linné partim. islandicus. If it is desired to cite the author of the new combination. definition. "(d) When the parents of the hybrid are not known as such (parents). and Dibothriocephalus latus (Linné. magellanicus. the exact original spelling. barbadensis. is the work which inaugurated . Example: Limnatis nilotica (Savigny. Ibañesia. "Article 26 . Example: Tetrao tetrix X Tetrao urogallus/Gallus gallus. a lapsus calami. Goeze. c j eki.Geographical names are to be given as substantives in the genitive. these follow after the author's name. namely. e "Article 16 .If it is desired to cite the subspecific name. burdigalenesis. 1758. this should follow the scientific nam e without interposition of any mark of punctuation. his name follows the parentheses . sensu stricto. however. with or without the sexual signs: "(a) The names of the two parents are united by the sign of multiplication (X) Example:Capra hircus male X Ovis aries female and Capra hircus X Ovis aries are equally good formulae. 1758. (Type by subsequent designation. when established. 1800. becomes ipso facto the type pe of the other. "(d) When an animal represents a regular succession of dissimilar generations which have been considered as belonging to different species or even to different genera. is accepted as the starting point of zoological nomenclature and of the law of priority. "Species which the author of the genus doubtfully referred to it. any subsequent author may select the type. "If a type was originally established for said genus. Example: Taenia pectinata Goeze. applied in the following order of precedence: "I.) "(b) If in the original publication of a genus. If the names are of the same date. but the species erroneously determined by Zeder. d) its type.If a genus is divided into two or more restricted genera. one of the species is definitely designated as a type. therefore. the ty of either. Cases in which the generic type is accepted solely upon the basis of the original publication: "(a) When in the original publication of a genus. "Article 29 . "Article 31 .The law of priority obtains and consequently the oldest available name is retained: "(a) When any part of an animal is named before the animal itself. that species or subspecies becomes ipso facto type of the genus. (Type by original designation. "Article 27 . such use shall be construed as 'type by original designation. Mention of a species as an illustration or example of a genus does not constitute a selection of a type.) "II.A genus formed by the union of two or more genera or subgenera takes the oldest valid generic or subgeneric name of its components. regardless of any other considerations. "Article 28 . typicus or typus is used as a new specific name for one of the species.The division of a species into two or more restricted species is subject to the same rules as the division of a genus. (Monotypical genera. "(b) When the larva is named before the adult. Cases in which the generic type is accepted not solely upon basis of original publication: "(e) The following species are excluded in determining the types of genera. The date 1758. (Type by absolute tautonymy.) "(d) If a genus. 1782 = Cittotaenia pectinata (Goeze). fails to designate (see a) or to indicate (see b. "Species which were not included under the generic name at the time of its original publication. that selected by the first reviser shall stand. its valid name must b e retained for one of the restricted genera. "Species which were species inquirendae from the standpoint of the author of the generic name at the time of its publication. "(c) When the two sexes of an animal have been considered as distinct species or even a s belonging to distinct genera. in publishing a genus with more than one valid species.Nomenclature and Classification 21 the consistent general application of the binary nomenclature in zoology.The designation of type species of genera shall be governed by the following rules (a to g). the latter species does not take the name Andrya pectinata (Zeder).) "The meaning of the expression 'select the type' is to be rigidly construed. the generic name is retained for the restricted genus containing said type. "(g) If an author. and such designation is not subject to change.' "(c) A genus proposed with a single original species takes that species as its type. without originally designated (see a) or indicated (see b) type. "(f) In case a generic name without originally d esignated type is proposed as substitute for another generic name. this species shall be accepted as type. with or without type. as Taenia pectinata ' Goeze' = Andrya rhopalocephala (Riehm). "Article 30 . But a specific name which undoubtedly rests upon an error o f identification cannot be retained for the misdetermined species even if the species in question are afterward placed in different genera. either a s valid name or synonym. . "The same rule obtained when two or more species or subspecies are united to form a singl e species or subspecies. contains among its original species one possessing the generic name as its specific or subspecific name. "Article 34 . oxyrhynchus. oe and e. Example: Taenia ovilla Rivolta.A generic name is to be rejected as a homonym when it has previously been used for some other genus of animals. is rejected as homonym of Trichina Meigen.) is rejected as homonym of T. insect. Example: Trichina Owen. Example: Names like Polyodon. 1830. however. 1879. Apus. is suppressed as a homonym and can never again be used. "Specific names of the same origin and meaning shall be considered homonyms if they ar e distinguished from each other only by the following differences: "(a) The use of ae. Thus.A name is not to be rejected because of tautonymy. "Article 36 . "(e) By the ending ensis and iensis to a geographical name. 1790. Such occurrences led the British Medical Journal in an editorial in 1926 to complain tha t "archaeoparasitologists" or: assiduous individuals have spent their days and nights ransacking musty archives and long-forgotten tombs.22 A History of Human Helminthology "Article 32 . Bilharzia haematobia. ovilla Gmelin. From these they have extracted a galaxy of paradoxically new yet old names which they have tacked on to the familiar names of our youth. c and k as microdon. auctumnalis. Not only was much of the literature inaccessible or unavailable. it was still-born and cannot be brough to life. ei. becomes valid upon the suppression of the homonymTaenia ovilla Rivolta. 1878 (n.Rejected homonymscan never be again used. once published. 1835. Taenia Giardi. cannot be rejected even by its author. "(d) By a single or double consonant. 1879. had to be altered to Schistosoma haematobium because the latter name was given to the parasite several months before Cobbold published his designation. later it was discovered that Taenia ovilla was preoccupied (Taenia ovilla Gmelin. "Article 33 . nematode. "(c) The presence or absence of a c before t. 1790). Example: Taenia Giardi Moniez. 1 Nevertheless. sp. 1878. when once published. A major difficulty . as timorensis. Examples:Trutta trutta. a name which had been used for decades to designate the worm discovered by Bilharz. mikrodon. etc. litoralis. timoriensis. Taenia ovilla. littoralis. which was suppressed as a synonym. as autumnalis. but there was ofte n .A generic or a specific name. even when the species is placed in another genus (Thysanosoma). Apus apus. ____________________________________________________________________ This applied whether or not a particular name was in common or popular use. such changes were essential if the rules were to produce th e uniformity and stability for which they were designed. lay in knowing who real ly said what about which worm. albus. the more recent specific or subspecific name is to be rejected as a homonym. i and y as chiropus. two different animals having the same specific or subspecific name are brought into one genus. "(b) The aspiration or non-aspiration of a consonant. cereleus. because of inappropriateness. cheiropus. "When in consequence of the union of two genera. that is. because the specific or the specific and subspecific names are identical with he generic name. as coeruleus. asoxyryncus.A specific name is to rejected as a homonym when it has previously been used for some other species of the same genus. 1878. was suppressed as a synonym of Taenia ovilla Rivolta. are not to be rejected because of a claim that they indicatecharacters contradictory to those possessed by the animals in question.. Rejected synonyms can again be used in case of the restoration of erroneously suppressed groups. "Article 35 . by which time it had been pre-occupied as th e name for a group of reptiles. Dipylidium. which will obviate the necessity for antiquarian research. not everyone was satisfied. type spinigerum. type medinensis. Similarly. An editorial in the British Medical Journal applauded this suggestion. Opinion 84 (16 December 1925): Dicrocoelium. for example . saginata . the International Commission o n Zoological Nomenclature appo inted a small advisory committee to consider the names of certain worms. In a series of opinions. type heterophyes. Ascaris. at the same time. Gnathostoma. the term "dracunculus" had been used in the vernacular sense until Cobbol d gave it generic status in 1864. type caninum. th e above-mentioned editorial concluded by observing that: What the mass of zoologists want is a system which will secure stability. grandis. type hepatica. Necator. Having begun by saying that zoological nomenclature was a sore point with everybody. especially the medical profession.type diminuta 25. Hymenolepis. Davainea. Again. type lanceolatum (vel dendriticum sub judice). they fixed the generic names of a number of helminths which were the subject of some contention: Opinion 66 (February 1915): Ancylostoma. Leiper (1926). to answer the question as to what really was the name first given to any animal29. Trichostrongylus. Opinion 77 (31 January 1922): Schistosoma. in Leiper's opinion. Taenia. or in other words. Fasciola. Nevertheless. Dracunculus. type retortaeformis 24. For example. specific names were sometimes abandoned without. type americanus. vernacular names were sometimes being used as generic or specific names. Taenia mediocanellata of Küchenmeister had bee n replaced by Taenia saginata of Goeze even though the latter had actually described the worm as Taenia cucurbitina. type solium 26. He regarded thi s state of affairs as intolerable and demanded that the International Com mission should use its plenary powers to suspend those rules which cause d greater confusion than conformity. Strongyloides.1 As a result of sentiments such as as these. Heterophyes. which. type lumbricoides. type proglottina. type stercoralis. type duodenale.Nomenclature and Classification 23 considerable doubt as to the acceptability or completeness of an accompanying description which would allow the organism to be identified with certainty. Echinococcus. Further. will reject enigmatical descriptions. he believed that steps should b e taken to press for an extension of this power by allowing well-establishe d names to be placed upon the list of accepted names 29. remarking that "there is no reason why such a list of names should be beyond the forensic powers of ou r biological and medical legislators" 2 but added with cynical realism that "W e ." 31 He declared that alterations flowing from the rule of priority had been a source of considerable annoyance to medical men and of bitter complaint from medical students. Leiper noted that one of the requisites of this law stated that the rules of binary nomenclature had to be applied but this was often not bein g observed. and will insist on the reference of all species to a central authority. declaimed against "the tyranny of nomenclatural rules in medicine. sufficient justification. type granulosus. Thus. type haematobium. that Leiper himself was no saint in these matters. This was published in London in 1961 with alternate pages set i n French and English and has set the seal on the nomenclature of animals 27. growth. not under the auspices of the International Commission on Zoological Nomenclature. comments such as these did have one solid effect. the XV International Congress of Zoology adopted a new . in order that they may be enabled to complete their development. In the case of a generic name. but as an opinion of the committee on terminology of the American Society o f Parasitologists when it reported in December 1940 that: It was of the opinion of the Committee that under the International Rules of Zoological Nomenclature Trichuris rather than Trichocephalus is the valid generic name. In July 1958. seu orthotype). seu condensed description) which differentiate or distinguish the genus from other genera or species. seu autogenotype. moreover. published after December 31. with a summary of characters (seu diagnosis. however. 1930. Human parasites are those which select the . 2. Nevertheless. And further 3. Küchenmeister in 185 5 defined parasites in the following manner: Parasites are independent organised beings. with the definite unambiguous designation of the type species (seu genotype. In order to leave no room for uncertainty as to the features of an organism being newl y named. unless and until it is published either 1. This word was derived from the Greek word (PARASITOS) which means literally "on e who eats at the table of another" and was formed by a combination of (PARA) = "besides" and (SITOS) = "food". or with a definite bibliographic reference to such summary of characters (seu diagnosis. to take up their abode either constantly or temporarily in or upon a second animal or vegetable organism of a different kind. which require. seu definition. seu definition. PARASITISM Another word in need of definition is the term "parasite". article 25: (c) But no generic name nor specific name. seu condensed description). complete official transcript of the International Code of Zoological Nomen clature. that Professor Leiper's pl ea will bring him neither tranquillity nor peace"2. from which they also derive their nourishment. the International Zoological Congress which met in Budapest in 1927 added a new section (c) to the law of priority.37 The committee also indicated that it felt that Dioctophyma renale was the correct name for the giant kidney worm which infects humans very rarely. for he sought to use the rules to his own advantag e when he attempted (unsuccessfully) to rename Dracunculus medinensis as Fuellebornius medinensis 30.24 A History of Human Helminthology fear. One major change in medical te rminology occurred subsequently. shall have any status of availability (hence also of validity) under the Rules. or reproduction. It ought to be added in parenthesis. descended from peculiar animal or vegetable parents. (Cited in 18). Küchenmeister (1855) believed that the most dangerous worms were larvae engaged in migratio n through the tissues. a flea Has smaller fleas that on him prey: And these have smaller still to bite 'em. then finally. Van Beneden also noted that whereas the beast of prey kills its victim in order to eat the flesh.4 The idea of a parasite was well-expressed in the lay literature in the lines o f Swift who. numbers and movement o f worms9..e.Nomenclature and Classification human body as this second organism. mess-mates and mutualists. small encysted worms 28. and very often his lodging.28 25 In a similar vein.. and whose only employment consists in taking advantage of him. and described them thus: The parasite is he whose profession it is to live at the expense of his neighbour. wrote: So. in response to the discovery by Leeuwenhoek when using hi s microscope that the fleas which infest man were in turn parasitized by mites . The mess-mate is he who is received at the table of his neighbour to partake with him of the produce of the day.7 These concepts find modern expression in the terms parasite.He is a pauper who needs help lest he should die on the public highway. on or within a living organism. He does not live at the expense of his host.. .. And so proceed ad infinitum PJ van Beneden (1889) recognized that there were varying relationships be tween two animals which lived in close relationship with each other. either with his consent or by force. With respect to the damage caused by these creatures. Cobbold (1864) wrote that: The happiest way of studying the entozoa is to regard them as a peculiar fauna destined to occupy an equally peculiar territory i. it is generally profitable f or the parasite if it does not kill its host. temporarily or permanently.The parasite instals himself either temporarily or definitively in the house of his neighbour. where th e organism does harm.. these were followed in turn by mature worms migrating in gut. Braun (1906) expressed modern concepts when he remarked that the pathogenicity of helminths was largely determined by the location.. where the two organisms assist each other in some way.13 while Braun (1906) penned: By the term parasites is understood living organisms which for the purposes of procuring food take up their abode. the interior of the bodies of man and animals. he demands from him his living. all that he desires is a home or his friend's superfluities. then large encysted worms. commensal. Mutualists are animals which live on each other without being either parasites or mess mates. where the organism neither helps nor hinders. He called them parasites. naturalists observe. and symbiote or mutualist. an d referred to obvious external agents such as pirates. we believe the terms 'infect' and 'infection' are properly applicable wherever the parasite invades and establishes itself within the body of the host. wolves. They concluded: We believe that 'infest' and 'infestation' ought to revert to their original use in connection with external. the American Society of Parasitology in 193 3 appointed a committee to investigate the matter.26 A History of Human Helminthology INFECTION VERSUS INFESTATION The word "infest" has sometimes been used instead of "infect" to denote th e presence of worms in a host. though this idea has never been used t o assert that non-invasive gastrointestinal bacterial infections should be calle d infestations. internal agents. there was a connotation o f trouble caused by invisible. These ideas were embodied in Dr. "taint" or "stain". the past participle of "inficere" meaning "to dip in"..g. vapours and miasmata.g . fungi and viruses became increasingly recognized. Samue l Johnson's Dictionary of 1785 whic h defined infect as to "act upon by contagion. protozoa. thieves. the past participle o f "infestare". as pathological processes due to organisms capable o f independent multiplication within the host such as bacteria. animals (e.. "infestations" of mosquitoes and the like. "Infect" and "infection" are derived from the Latin word "infectus".said of persons (e. unsafe. On the other hand.We fail to see any reason for continuing the use of the term 'infestation' as applied to internal parasites and believe that the present confusion will disappear only as its use be discontinued. visible agents. There would be retained the long established use of these terms in connection with most insects in speaking of such conditions as dogs "infested" with fleas. Further. to taint. The same concepts are enjoined in the modern Oxford Englis h Dictionary which gives the meaning of infect as "to affect (a person. and in most cases. the gastro-intestinal tract. or contamination with noxious effluvia. meaning "to make hostile. "put into". Nevertheless. vermin. to pollute" while to infest was "to harass." 3 This concept has largely held sway and most technical works now refer to helminth infection s . robbers. to poison. "Infest" and "infestation" on th e other hand. This would apply then. disturbed or troublesome". the argument was expressed that intestina l worms are not truly within the body. t o plague".. Thus. pirate).. while infestation was proposed for thos e organisms which do not (or usually do not) multiply within the host such a s helminths and insects. including in this sense. animal or part of a body) with disease" while to infest is "to trouble (a country or place) with hostile attacks. diseases or other evils". 36 This view was supported in 1960 by an editorial in the British Medical Journal which remarked that "Consistency and common sense would therefore seem to favour the use of the word infection for intestinal helminths... there was an attempt to limit the term infection to such organisms. to disturb. Its use long antedated the knowledge of pathogeni c microorganisms and implied tainting with morbid matter. not only to bacteria and protozoa. are derived from the Latin word "infestus". rats and fleas which molested or harassed the victim. insects). In view of this confusion. but also to helminths. Traité de zoologie médicale. Tableau élémentaire de l'histoire naturelle des animaux. 8 volumes. translated by P Falck. 14. Parasites and parasitic infections in early medicine and science. Systema helminthum. Librairie encyclopédique de Roret. two volumes. Sons and Danielsson . pp 966. ordines. Smithsonia n Institution Publication 2359. 4. more particularly. pp 171-176. pp 780. 1788-1793 GOEZE JAE. PA Pape. Paris. CUPP EW. 1845 FAUST EC. 7. London. University o f Malaya Press. 1948-1953 COBBOLD TS. 1889 BLANCHARD R. Loeb Classical Library. pp 453. 1782 HIPPOCRATES. Loeb Classica l Library. 16. London. De removendis nocumentis in regimine sanitas. Id est. 17. The nomenclature of parasitology. Paris. 1855-1857. edited by KG Kühn (Greek text with Latin translation). 23. graece et latine. 1939 GALENUS CC. 1864 CUVIER JG. 1910 ANONYMOUS. London. Venetiis. 11. Ein Buch für ausübend e Aertze. pp 3021-3909. London. Libri in re medica omnes. 1926 ANONYMOUS. fourth edition. V Valgrisius. p p 1691. second edition. Washington. Heinemann. Entozoa: an introduction to the study of helminthology with reference. Bohn's Classical Library.. 19. Human helminthology. pp 526. Histoire naturelle des helminthes ou vers intestinaux. Wilhelmum Braumüller. E Heitz and UC Bussemaker (Editors). Paris. CELSUS AC. Lipsiae. pp 480. pp 471. Philadelphia. Heinemann. 1821-1833 GMELIN JF. Henry Kimpton. 21. 1877 DIESING CM. 2. second edition. pp 825. thirteenth edition. JUNG RC. locis. to the internal parasites of man. six volumes. pp 284. pp 1267. cum indice nominum et rerum absolutissimo. 1948-1953 HOEPPLI R. 18. Works of. 13. translated by WH Jones and ET Whithington. Groombridge and Sons. synonymis. 1000 AD BEAVER PC. Ueber lebende Würmer im lebenden Menschen. 15. 12. A manual for physicians. Works of. J-B Baillière et fils. Versuch einer Naturgeschichte der Eingeweidewürmer thierischer Körper. J-B Baillière et fils. ANONYMOUS. 1819 CAIUS PLINIUS SECUNDUS. 27 REFERENCES 1. five volumes. DC. Didot. revised by LW Sambon and FV Theobald. genera . De viribus cordis. Wien. Mit nach der Natur gezeichneten Abbildungen auf vier Tafeln. Parisiis. Original arabic "Al Canon fi al Tib" c. 1984 van BENEDEN PJ. Historia naturalis. libri canoni s quinque. qui hactenus ad nos pervenere. 1798 DAVAINE C. F Dübner. pp 652. 10. sanitarians and medica l zoologists. Traité des entozaires et des maladies vermineuses de l'homme et des animaux domestiques. Kegan Paul. 1960 ARISTOTLE. two volumes. Paris. . London. London. 1915 6.Nomenclature and Classification rather than infestations. translated by WG Spencer. four volumes. Animal parasites and mess-mates. species. De sirupo acetosa et cautica. 1564. Lea and Febiger. Leipzig. Tranch and Co. Infect and infest. pp 274. three volumes. The animal parasites of man. 3. British Medical Journal ii: 1129. 1849-1851 DUJARDIN F. Blankenburg. secundum classes. 1906 BREMSER JG. British Medical Journal ii: 1724. cum characteribus differentiis. Zoological nomenclature. De medicina. Nematode and Gordiacea names placed in the official list of generic names (Opinion 66). Carl Schaumburg und Comp. pp 1003. translated by JP Mongio Hydruntino et J Costaeo Laudens. Vindobonae.. GE Beer. 24. 1959 INTERNATIONAL COMMISSION ON ZOOLOGICAL NOMENCLATURE. 5. 1885-1890 BRAUN M. Systema naturae per regna tria naturae. In: Medicorum Graecorum opera quae exstant. ninth edition. Nebst einem Anhange über Pseudo-Helminthen. 1848-1874 AVICENNA. London. 20. British Medical Journal ii: 1989-1990. 20 volumes. Clinical parasitology. translated by J Bostock and HT Riley . John Bale. 22. 8. A ha ndbook for students and medical men. 9. Opera omnia. Coelenterata. 1800 44. translated byE Lankester. 1922 26. differentiis. 1852 39.. INTERNATIONAL COMMISSION ON ZOOLOGICAL NOMENCLATURE. Élémens de pathologie médicale. London. La parasitologie dans la littérature antique. RUDOLPHI CA. pp 176. Cited in. 1961 28. 1735 33. Also. Berolini. ZEDER JG. p 193. pp 452. 73: 11-12. pp 320. two volumes. REPORT OF THE COMMITTEE ON TERMINOLOGY. Cirrepoda. Paris. Trematode. RUDOLPHI CA. Zoological nomenclature in medical literature. 1937 37. 1926 27. Naturgeschichte der lebenden und untergegangen Thiere . Indian Medical Gazette 51: 165-173.und Tropen-Hygiene 30: 484-491. Cestoda. two volumes. locis. REPORT OF THE COMMITTEE ON NOMENCLATURE. KÜCHENMEISTER F. 1808-1810 40. Cestode and Acanthocephala names placed in the official list of generic names (Opinion 84). Venetiis. Volume 1. Journal of Parasitology 27: 277.28 A History of Human Helminthology 25. Ein Lehr. BG Teubner. 1911 35. Infection vs.und Handbuch der Diagnose und Behandlung der thierischen un d pflanzischen Parasiten des Menschen. MOULÉ L. Journal of Parasitology 23: 325-326. Siegfrie d Lebrecht Crusius. 1916 30. Practi a etc. Thirty five generic names in Protozoa. 1855. Washington. species cum characteribus. 1851 43. Smithsonian Miscellaneou s Collections. 1941 38. 1668 36. sive vermium intestin alium historia naturalis. 1819 41. DC. 73: 71-73. ordines. A manual of their natural history. The Sydenham Society. Holmiae. International code of zoological nomenclature adopted by the XV International Congress of Zoology . diagnosis and treatment. Anleitung zur Naturgeschichte der Eingeweidewürmer. Trichocephalus Schrank 1788. Animal parasites belonging to the group Entozoa. Cited c in 23 42. DC. genera et species. translated. infestation. 1803 . Paris. LINNAEUS C. Trematoda. tenth edition. Washington. 1926 31. LEIPER RT. pp 432. ordines. Publication 2657. Smithsonian Institution. JAE Goeze's Erster Nachtrag zur Naturgeschichte der Eingeweidewürmer mi t Zusätzen und Anmerkungen herausgegeben von Johan Georg Heinrich Zeder. Tunicata and Pisces placed in the official list of generic names (Opinion 77).. Archiv für Schiffs. two volumes. three volumes. Leipzig. INTERNATIONAL COMMISSION ON ZOOLOGICAL NOMENCLATURE. Entozoorum. Discussion on the validity of certain generic names at present in use in medical helminthology. pp 823. secundum classes. or some physical Considerations of the Matter. Elminthologia. Treuttel & Würtz. Bamberg. LANE C The correct names of the helminths of man. Origination. Frankfurt. L Salvii. Publication 2830. genera . Archives de Parasitologie 14: 353-383. British Medical Journal ii: 1122-1123. and Several Species of Wormes macerating and Direfully Cruciating every part ofthe Bodies of Mankind etc. pp 1370. London. Die in und an dem Körper des lebenden Menschen vorkommende n Parasiten. II Les parasites du tube digestif . International Trust for Zoological Nomenclature. SERAPION (YUHANNA IBN SARA-BIYUN). Leipzig. Entozoorum synopsis cui accedunt mantissima duplex et indice s locupletissima. RAMSAY W. Systema naturae. Trichuris Roederer 1761 vs. Zoologische Briefe. 1497. sive regna tria naturae systematice proposita per classes . INTERNATIONAL COMMISSION ON Z OOLOGICAL NOMENCLATURE. LINNAEUS C. volume 3. ZEDER JG. Sumtibus Augusti Rücker. Smithsonian Institution. 1925. VOGT C. LEIPER RT. synonymis. first edition. On animal and vegetable parasites of the human body. 1857 29. 1758 34. Smithsonian Miscellaneous Collections. Lugduni Batavorum. Theodorum Haak. REQUIN AP. pp 486. 279-282. Nature 117: 414. 1926 32. pp 811. Systema naturae per regna tria naturae. Chapter 2 UNDERSTANDING THE ORIGIN AND TRANSMISSION OF WORMS The finding of worms within the bodies of humans and animals inevitably led to questions concerning how those so afflicted became infected. This process of "spontaneous generation". The first was the invention of the microscope which allowed discovery of th e presence of ova and spermatozoa and demonstration of the cellular basis o f animals. the most comfortable and gen erally accepted explanation given was that the parasites had arisen by a process of spontaneous generation. and the argument was only settled when the second factor. How else could the sudden appearance of mus hrooms after a heavy rain or the plague of locusts or rodents in certain seasons be explained? As has been described in th e 29 . In particular. As will be shown. including helminths. "abiogenesis" provided the simples t and most obvious explanation for many puzzling observations. There were two key factors which determined the outcome of this conflict of opinion. this was not enough t o persuade many students of the subject. sometimes known a s "equivocal generation" or. and a critical battle raged for over a century and a half from the late seventeenth century until near the middle of the nineteenth century before the protagonists of this theory were finally silenced. the events leading to the demonstration of the phenomenon of alternation of generations in trematodes are reviewed in chapter 4 while the controversy that led to the recognition of th e relationship between cystic w orms and tapeworms is covered in chapter 12. FROM EARLY TIMES TO THE MIDDLE OF THE SEVENTEENT H CENTURY Belief in the spontaneous generation of certain plants and animals goes back to ancient times and probably began when man started to speculate on the origins of life. How and when these various discoveries were m ade are recounted for specific worms in the various chapters that follow. even after it was agreed that wor ms multiplied by sexual and asexual processes. more latterly. Nevertheless. experiment. was introdu ced into helminthology. For much o f recorded history. the present chapter attempts to provide the historical sequence in which thes e disparate threads unfolded and the interpretations which they engendered in the minds of helminthologists. many years often elapsed before the precise details of the mode of transmission of a particular parasite were defined. This was a theory not easily denied. . espe cially under the influence of fever 77. Concepts like these were behind the Old Testament accounts of the plagues of Egypt such as the derivation of frogs from water and insects from dust (Exodus 8). Similar ideas were found in the Orient. considered that worms arose in the humours 155. . Oribasius (325-403 AD).. particul arly as it applied to arthropods. In India. do not generate offspring identical with their parents... In the same vein. 6 Many Romans. Similarly. The Greeks and Romans in the centuries around the time of Christ wer e equally at home with such ideas. moisture. or excessive warmth 83.. In particular. but out of putrescent soil and out of residues. Examples of such beliefs have been recorded from many regions of th e ancient world.there are. accepted this doctrine of spontaneous generation. several intestinal roundworms and tapeworms have bee n recognized for millenia and these were regarded as an excellent proof of thi s doctrine. considering that they took their origin from the gut contents 64. Likewise. "aura".460-375 BC) regarded intestinal worms as originating in excrements in the fetus before birth 76. the story is told how Samso n killed a lion with his bare hands.. insufficient exercise. for it seemed impossible to account in any other way for the existence of such large organisms in the human intestine. Ovid. then on returning to the scene after a tryst with his beloved. ancient Babylonian texts have been found which alleged that worms were generated from the mud of canals 118. solids)... Galen (129-c. these he regarded as a dead end: Among the bloodless animals. physician to the emperor Julian th e Apostate. Pliny and Celsus. Maggots an d intestinal worms were thought by them to be produced from decomposing food and putrefying wounds in the intestines. includin g spontaneous generation.30 A History of Human Helminthology previous chapter. the Persians of old believed that bees were generated in the dead bodies of bulls 58. Ascaris in the bilious humour. groups which. although they generate.. phlegm. According to Aldrovandi2.(some) insects moreover are not produced out of animals at all but out of putrefying fluids (in some cases.200 AD) believed in the spontaneous generation of intestina l helminths. Hippocrates (c. even if they produced offspring of a sort. In China. the ancient Egyptians believed that the sacred copro phagous scarab beetles took their origin from balls of dung. insects. as they clearly had not bee n ingested as such. and blood as a result of a poor diet. He claimed that many worms. in Judges 14: 5-9. bad sleeping habits. Such are the creatures which come into being not as the result of the copulation of living animals. Aristotle (384-322 BC) considered that there were four kinds of generation. bed bugs were thought to be derived from blood while intestinal worms were assumed to have arisen from faeces. Oribasius regarded Enterobius as arising in the black humour . Thus. intestinal worms wer e considered to be the result of transformation of stagnating food in the bowe l under the influence of heat. including Virgil. and wind 77. sponges an d coelenterates arose in this way. Likewise. found the carcass swarming with bees and honey. and tapeworms in the mucous humour. .1300) 198..On account of its stickiness which makes it adherent to the intestines. it undergoes still further putrefaction wherefrom worms are produced and . propounded a novel explanation for the existence of these worms. sticky and crude material which decomposes in the stomach and then descends into the intestines. long.160 Thus. one of the fathers of modern surgery. Likewise. Some are formed from moisture not divided or broken up by attraction of the liver. Th e Arabians of the Dark and Middle Ages provided the prime link between th e literature of the past and the Renaissance in Europe. This belief in the influence of temperature was taken up by other writers such a s Gabucinus (1547) who wrote that the lower temperature of the intestine led to the formation of tapeworms 63. a bird could be recreated from its own ashes in horse manure . and short. all animal s and even man could be produced by spontaneous generation. Al-Qaz wini (died 1283). From this comes rebirth and a new birth with thousandfold improvement. Avicenna even believed that with a proper mixing of the element s and under the influence of the stars.Origin and Migration of Worms 31 These beliefs persisted into the Middle Ages and the Renaissance. Another Arab. some are formed by an intermediate condition. it cannot be discharged from the abdomen. Cardanus believed that slow putrefaction produced lower animals such a s worms while rapid putrefaction resulted in higher animals such as birds 33. Thus.. c. These concepts were accepted by a number of European writers of the Middle Ages such as Albertus Magnus (Albert von Baellstaedt. Avicenna (Ibn Sina ) (980-1037) was convinced that intestinal worms arose from the intestina l contents in combination with moisture and various other factors: There are four kinds of worms. broad worms i n "sweet Fleghm". round worms bred from "salt Fleghm". Others are formed from moisture divided or broken up by the attraction of the liver and fermentation. because putrefaction is a reversal and death of all things and a destruction of the original character of all natural things.Thirdly. while a pigmy could be similarly produced fro m putrefied human sperm if it was kept under the correct conditions.. Being retained. round worms in "sharp Fleghm". short.. c. broad worms in "natural Fleghm or Mucus" 198. Paracelsus considered that worms were produced from "sperma" an d putrefaction.8 Moreover... Villanovanus (Arnauld de Villeneuve. or excess of fermentation.. believed that intestinal worms were created by spontaneous generation in decomposing humours: The worms are formed by a thick.They are different because of different origin and surrounding. He suggested that divine wisdom determined that parasites should take their origin from putrefyin g substances so that they could absorb them as food and hence purify the air and prevent epidemic diseases 3. Paracelsus (1493-1541) had similar fantastic ideas: many things will be changed in putrefaction so that they give birth to a noble fruit.. Villanovanus considered that there were four kinds of worms: long. Edward Wotton 33 (1492-1555) 207 and Cardanus of Pavia (1501-1576) . Ambroise Paré. while Mercurialis (1623) claimed that different temperatures influenced the formation of small and large intestinal worms 130.1193-1280) 9. reptiles and fish were escaping.. dryness. all under the influence of a vital force. all being influenced in an undefined way by some special principle. These basic concepts wer e systematized in various theories.32 A History of Human Helminthology take their origin by the action of the warmth.. Common threads can be discerned in these writings over the centuries. in decomposing substances. This statement adorned an opened egg h eld by Jove from which many creatures. moisture) and the four humours (blood. air. and this is the same as that which is found in the semina of congenerative animals.For even in fortuitous semina there is an inherent motive principle of generation. "archaeus" (Paracelsus). In any case. water. which procreates from itself and of itself. considered that al l matter was composed of minute un its or atoms. and tapeworms arose in thick. William Harvey (1578-1657). spontaneous generation took place. Democritus (c. 74 In fact. he was an Aristotelian and at times use d language which is entirely consistent with a belief in spontaneous generation.. viscous phlegm185. phlegm. a power to wit. and that when these atoms were agglomerated and amalgamated by a special force.460-360 BC) and Epicurus (341-270 BC). "principe vital" (Theophile d e . the words which appeared on the allegorical title-page of his De generatione animalium were "Ex ovo omnia" (all creatures come from an egg). roundworms were dependent upon phlegm and bile.. such as the Greeks. the four qu alities (heat. "pneuma" (Plato and others). Most authors considered that intestinal worms arose in the gut contents wherea s ectoparasites were produced by perspiration and dirt. When the balance and harmony between microcosm and macrocosm were disturbed. embryos of man. "physis" (Hippocrates) .. He considered that this occurred as a consequence of a special principle existing in putrescent material: Many animals.161 Spigelius (Adrian van der Spiegel) wrote in 1618 that pinworms were produced by a mixture of phlegm and ex crements at the proper temperature. A variation upon this theme was expounded by Aristotle who proclaimed that spontaneous generation occurred when there was a disharmony of the four elements (fire. yellow bile. Harvey had no t seen the minute ova of viviparous creatures and he may well have been using the image figuratively 183. Moreover. especially insects.are supposed to have arisen spontaneously. believed that "imperfect animals" such as worms and insect s arose by spontaneous generation. "psyche" (Plato and Aristotle). Others. "virtus vivificata" (Albertus Magnus). disease occurred and parasites were created. earth). cold. black bile). of forming a living creature. despite the doctrine of "omne vivum ex ovo" (all life comes out of eggs) attributed mistakenly to him by many subsequen t commentators. This "vital force" has been given many names including "nous" (Anaxagorus). mammals. or from decomposition because their ova are nowhere to be found. Certain Western and Eastern schools o f thought regarded Man as a microcosm which took its origin in the macrocosm. Harvey was more concerned with embryological development than with the origin of generation. His postulate that in higher animals the organs are successively formed out of the indifferent matter in the egg came to be known as "epigenesis".. court physician to the Duke of Tuscany. particularly in th e first half of the eighteenth century. Thus. only refuted error with error. It was around this period that the doctrine of "preformation" was evolved. in propounding his "principle of plenitude" wrote: all the bodies of men and beasts. THE SECOND HALF OF THE SEVENTEENTH CENTURY Not everyone was happy with such ideas. for example. 125 This concept of preformation was then applied to the origin of worms. it wa s believed that the vital force either created living creatures directly out of its own metaphysical properties or it generated them by its action upon primordia l matter. Thus. Redi could not accept the view that "worms" were produced in dead animals or plants but postulated that they were generated by insemination in putrefying matter.127. then the theme was taken up by others. Sir Thoma s Browne (1645) questioned "whether mice may be bred by putrefaction?" 27 Browne. however. as will be described later. Eve was considered to contain within her gonads the forms of all the men and women that wer e ever to be. In general. published in 1668 his monumental work. Thus. in its own ovaries. This led to the supposition that a complete being lay in an egg and only a suitable stimulus was required to cause it to unfold. however. or at least with opinions that seemed more reasonable than did the original ones. egg s which in turn held secondary ova and so on. believed that he could discern the form of an embryo in an unincubated egg126.Origin and Migration of Worms 33 Bordeu) and "Lebenskraft" (F riedrich Casimir Medicus). however. were possibly created from the beginning of it. Marcell o Malpighi. Both of these fac tors were ultimately to have immense effects on the acceptance of the theory of spontaneous generation. The theory first appeared in the scientific literature in Swammerdam's book on insects in 1669189. The central thesis of preformation was that the act of procreation merely permitted the appearance in an organized and formed state of a being that was already pre-existent . de Malebranche in 1673. This view extended to the concept of "emboitement" or "syngenesis" i n which it was held that the being in the egg held. It was at this stage that two events of epochal importance occurred: (1) Redi began to experiment on the origin of invertebrate animals and (2) th e microscope was invented then its use in microbiology popularized b y Leeuwenhoek. Esperienze intorno alla generazione degl'insett i (Experiments on the generation of insects )169. the latter merely serving . which shall be born or produced till the end of the world. but this led to all sorts of philosophical and theological difficulties. Francisco Redi. The way in which this invisible and imperceptible vital principle was supposed to act was described differently by the various schools of philosophy. Thereupon. so he separated them into different glass container s covered with paper. sometimes all k inds.. and not from the putrefactions of meat.. remarking "Belief would be vain without the confirmation of experiment" 169. large. each into separate. He not onl y showed that maggots were not bred spontaneously from meat. then a duplicate serie s was set up except that the mouth of each vessel was left open to the atmosphere. but was unable to demonstrate any way in which eggs could enter a plant. he also observed that the meats became covered with true eggs fr om which the maggots hatched. som e fish. He noticed that some of the worms became quiet. Redi made a crucial step. He began with the same hypothesis as he had proven with flies on meat. wide-mouthed flasks. Thereupon. some eels and a slice of veal from a m ilk-fed cow. he found that they were covered with maggots (which he called worms). the maggot s disappeared. Furthermore. but traced th e development of eggs through larval and pupal sta ges to adulthood. the same kind of fly appearing from the same type of pupa . He watched and found that no maggots developed in the closed flasks whereas flies entered and left the open containers at will and maggots eventuall y appeared. In contrast to his predecessors . he killed three snakes and placed them in an open box to decay . I began to believe that all worms found in meat were derived directly from the droppings of flies. Redi undertook a large number of experiments in order to test thi s view.169 . and in every case the result was the same with one or othe r kind of fly developing. Once all the meat had been consumed.34 A History of Human Helminthology as a suitable nest in which animals could deposit their eggs and in which th e resultant offspring could find nourishment. This led him to the conclusion: Having considered these things. he put a snake. he recognized that there was a variety of shapes amongst these pupae. appeared to shrink and assumed a shape similar to an egg. This led him back to an acceptance of spontaneous generation for these creatures: Hence I have changed my opinion and I think it probable that the generation of worms in trees does not. on this occasion. Each flask was carefully sealed. 169 This seemed especially likely as flies of the same kind as those that were bred had hovered over the meat before it grew maggotty. it must be conceded that Redi was led astray in his studies of the appearance of larvae in galls on plants. he repeated the experiments on many occasions with various kind of dead animals. After a week or so. compare d with other observers. In order to determine what had become of them. Soon afterwards.proceed from the eggs deposited by flies. however. Redi repeated these experiments on many occasions. however. First. he covered ev ery exit from the box. 169 Redi believed that the principle which created the flowers and fruit in the first place was the same as that which produced the grubs: the efficient cause resided in the peculiar potency of that kind of soil or principle which creates the flowers and fruits of living plants. the shells of the eggs (pupae) broke and flies came forth. Moreover. and is the same that produces the worms of these plants. Nevertheless.. Nevertheless. he repeated the experiment but. which he described as indicating "univoca l generation". The experiments and observations of these two pioneers were to prove turning points in the understanding of the origin of "lesser animals". writing in 1683. Edward Tyson. in the whole world as is known besides. tho' they have much advanced the doctrine of univocal generation. putrefaction. or of the same Species. that are received with food or in other ways. out of the body. i. In 1669. 169 Thus. there is nothing more plain. Redi thought that worms found in the intestines and other parts o f humans probably arose in an analogous fashion by spontaneous generatio n through the agency of the same vital force: In this same manner it could perhaps be true.e. that are bred in Animal bodies not such as we may suppose to be hatched from the eggs of the like kind.194 This problem was so insuperable for Tyson that he ended the title of his paper . 194 Tyson demonstrated the sexual apparatus o f roundworms (Ascaris lumbricoides which he called Lumbricus teres) by dissection and believed that once present in the gut. these worms reproduced sexually: yet once there.Origin and Migration of Worms 35 Moreover. that insects found in various plant galls resulted from eggs laid by certain flies. how to account for several of those. Redi showed clearly that some parasites arose from ova. Moreover. Jan Swammerdam. there being in this Sort so perfect a Distinction of Sexes. are born the lumbricoids and flesh worms.195 Tyson had greater trouble with tapeworms. but with whom we cannot meet with a parallel. natural generation from the same type of organism: The consideration of Insects. that in the intestines and other parts of man. He demonstrated clearly. He studied in detail their anatomy. The Englishman. and I feel disposed to believe it. as it is a subject of curious speculation. and he noted that certain parasitic "worms" sometime s found in caterpillars or butterflies were the offspring of other insect s (Ichneumon flies) that were in the habit of laying their eggs beneath the skin of the caterpillars 189. than that the Lumbricus Teres propogated by univocal Generation. of their production from. was well aware of th e studies of Redi and others. Male and Female. but he could find no evidence of two sexes. Redi's experiments were soon followed by publication of the observations of the Dutchman. he published his Algemeene verhandeling von bloedloose diertjens (General account of bloodless ani malculae) which dealt with the modes of transformation of insects and high lighted the different manner of development of the various types of insects. so of late hath been much illustrated by the laborious researches of many inquisitive persons: whose travels therein. too easily received. He also showed that the pupa was not an egg but a stage in development of the life cycle of a single individual. that lic e developed from eggs. and bid very fair the exploding of that. he could not conceive how these organs could have had their origins fro m outside of the body for they resembled nothing in the external world: yet one great difficulty still remains with me. and common error. and their manner of generation. discovering their head. for example. as they were commonly known at that time. but concede d that other parasites may arise by a process akin to spontaneous generation. h e examined green sods from a meadow on which some infected sheep had fed and looked for microscopical creatures resembling flukes. In 1673. Meanwhile. in the Philosophical Transactions of the Royal Society . and the ways in which animal tissues were organized. Swammerdam. Hans and Zacharias Janssens of Middleburg. observations that many o f the innumerable small organisms found in water and moist soil resembled helminths led naturally to the conjecture by many helminthologists that. the invention of the microscope had opened up a new world of microorganisms. but Harting 72 concluded that the accolade probably belongs to the Dutchman. the morphology of the eye of the bee. Nevertheless. both correctly and in error. Cornelius Drebbel of Almaar. Leeuwenhoek sent letters to the Royal Society covering an eno rmous field of observations on microscopic biological matters101. Antony van Leeuwenhoek (1632-1723). however. as a difficulty against the doctrine o f univocal generation" 194. but the use of suc h lenses in microscopes first took place around the end of the sixteenth or th e beginning of the seventeenth century. will be traced in the followin g sections. and the microscopical appearances of lice. Little heed was paid at first to this innovation but it began to be used by a number of scientists including the Englishmen. or hi s countrymen. It is difficult to assign proper credit for the invention of this instrument. These new vistas wer e ultimately to sound the death knell for the theory of spontaneous generation. and the Italian. Most of these workers concentrated o n microscopical aspects of macroscopic plants and animals. he published his first paper. Being aware of the general belief that Fasciola infection was acquired by animals feeding on contaminated pastures. the manner in which new life was produced. Marcello Malpighi (1628-1694). Not only did he describe in abundance the group o f unicellular organisms now known as protozoa. but failed to find any 100. and the real discoverer of the invisible world of microscopical living creatures was th e Dutch microscopist. Furthermore.36 A History of Human Helminthology with the words "and the whole urged. after their almost unavoidable introduction in th e human system. Leeuwenhoe k made his own microscopes and improved upon their optics. Over th e next fifty years. Thomas Huxley suggested many years later that this demonstration of the abundance of microorganisms with thei r manifest provision for multiplication made it seem to many observers that the doctrine of spontaneous generation was not only untrue but also absurd 80. but he was the first to visualize bacteria. which dealt with mould. the Dutchman. . It is not known with certainty wh o invented the compound microscope. The art of making convex and concave lenses had long been learnt. The evolution of such ideas. Robert Hooke (1653-1703) and Nehemiah Grew (1641-1712). these creatures would grow into parasitic worms. a feat which was not repeated until improvements in microscope s made it possible for others to see them. Leeuwenhoek himself was a preformationist and a firm opponent of the theory of spontaneous generation. this technology was essential for the demon stration of ova and spermatozoa. by means of a seed that enters there. and so be free of them. and that a great Quantity of them may enter into the body of Man.. Andry went to see a thirt y year old man with fever. as to the course o f events once the seed entered a body. into which the seeds of insects may not insinuate itself. whethe r natural or acquired. as well as other small living creatures. and put in the first individuals of the species. It must be admitted that Andry based his arguments upon logic and philosophy rather than upon experimentation.Origin and Migration of Worms 37 As the century drew to a close. whose body abounds with a certain sort of Humour. there were still many staunch believers in the theory of spontaneous generation. are produced from their like.the skin is full of cavities. For all animals. THE FIRST HALF OF THE EIGHTEENTH CENTURY The new century saw the publication in 1700 of a book on helminthology b y Nicholas Andry in which he attempted stoutly to refute the theory of spont aneous generation. however.16 and considered that these "seeds" were ingested in contaminated water.5 Next.... no doubt girded by his discovery of eggs in Fasciola. by means of the Air and Aliments. as well as into those of other Animals.. But the o pponents were becoming more vocal and were exemplified by Bidloo. in which those worms are enclosed. haemoptysis.they likewise enter the Flesh very often by the outside. he discussed the manner in which these "seeds" could enter human an d other animal bodies: there is nothing in Nature. and that Microscopes discover them to us sometimes quite formed. for he appears to have believed that th e internal milieu determined the type of worm that developed: a Man.. whilst he who abounds with another Humour. contains in no little Bulk. left-sided chest pain and dyspnoea who five days later became delirious and passed a tapeworm 4 ells 3 inches long (an English ell is 45" [113 cm] and a Flemish ell is 27" [68 cm]).. that was to become so important 200 years later. 5 Andry went on to consider whence this "seed" first arose: the seeds of all Animals were created by the first Being.. will produce none.. that these.are bred of a seed which contains them.5 By the latter remark. the Animal that is to be formed in it. 5 Andry seems to have become a little confused. will produce Worms of another. Andry firs t defined worms then went on to a consideration of their origins: Worms breed in the bodies of men and other animals. Andry foreshadowed the concept of immunity... seed or spawn. who.this Seed of Animals. and he who has no Humour proper for the Eggs of Worms. will produce Worms of a certain sort. as is exemplified by his challenge to the proponents of . Andry had been stimulated to write his book following a n incident with one of his patients. according to the nature implanted in them at their first creation. On 4 June 1698. by the means of eggs. in 1698 laid it: down as a certain truth.. pretend that the worms and several other Insects are bred of Corruption.. This created appalling theological problem s and Vallisnerius put the issues: It is not reasonable to suppose that God would have placed the first worm in his body... Worms Eggs lying hid in the Intestines are enliven'd and brought forth..11 Clericus (1721) accepted the views of Redi .But if on the other hand. the first man. and the other.. and to fal l upon some Herb or other thing... On 26 February 1699. after the lapsed state of Adam.. in whose Intreals the Worms contain'd in those Eggs come forth and are fed. and nothing is ever engendered by corruption. parasitic worms ate contentedly from Adam's superfluities and even performed good works by gently licking any holes in the gut and healing them. Vallisnerius was in fact a proponent of "emboitement" which was mentioned earlier. vigorously opposed the views of Andry and endeavoured to explain the presence of entozoa by supposing them to be transmitted from parent t o child via the placenta or through the breast milk 197.. Mr Niklaas Hartsoeker of Amsterdam had written to him: There's nothing has life. however. 197 Vallisnerius attempted to solve this dilemma by assuming that before the Fall. A logical extension of this theory was that Adam.. but which comes from Seed. But if these Philosophers could explain to me two things. the one how casual disorder could range with so much order the Organical parts of Animals.. But when Adam fell: all things were suddenly changed. only by a Fortuitous Combination of Matter without any seed. are swallowed by another.. we allow that worms were formed by God.Since no Man says that Plants rise from Putrefaction. harboured not only all mankind to be. from whence it comes that we see no new Species of Insect bred. Vallisnerius... and that some of their coming to issue with the Excrements. forasmuch as Man in this state of innocence was to be free of all kinds of diseases.73 In like manner. If it proceeds from an Egg?... all other animals were created. Andry and those of like mind.38 A History of Human Helminthology spontaneous generation: Some Philosophers. Andry included quotations from two of his correspondents.. Giorgio Baglivi in Rome wrote on 14 July of the same year: You ask me 1... be it Animal or Plant. so that these worms were made Ministers of Divine justice and raised an insurrection upon him. but all of his worms as well..it will follow that God made a new creation of worms. which is contrary to Holy Writ. to wit.. since God hath taught us.. Not everyone was convinced by these arguments..for..197 . that before Man was made. for example. Therefore the Flat Worm derives its Original from an Egg of its own kind. since that must happen according to their System.I am of the opinion that those Worms ingender by Male and Female in the Bowels.5 In order to support his arguments. but considered that "The most difficu lt Question remains yet to be discussed.The beginning and original of all Animals and Vegetables is from an Egg... a greater difficulty will arise.. they ought not in reason to deduce the Original of Insects and other baser Animals from thence. From whence the first Seed of Worms is derived" 37. . was easily destroyed by boiling for half a minute.30 Similar views were expressed by Needham in Britain. In 1749. Needham undertoo k some experiments which he interpreted as supporting these concepts. Buffon's monumental Histoire Naturelle began to appear in France30. One. men like Boerhaave 20 and Hoffmann78 erroneously traced many cestodes an d nematodes back to microscopic animals which in their free state were totall y different in appearance to the parasitic adult worms. he claimed to see a swarm of minute..This is the origin of tapeworms. Needha m repeated the experiment with hot mutton gravy which. Lazzarro Spallanzani (1729-1799) who undertook numerous. Thus. Similar results were obtained in othe r experiments and Needham concluded that the organisms derived from a "vegetative force in every microscopic po int of matter and every visible filament of which the whole animal or vegetable texture consists" 146. well-conceived experiments which included heating infusions as well as hermetically-sealin g them. which was exceedingly minute microscopically and which he calle d ultime ordini. were rearranged to constitute vitality: excess molecules. reunite with several particles of brute matter in the food and form organized bodies. which he called ordini superior i (superior order). moving objects of "animalcules" which he believed came from the almond. Buffon developed the idea that vitality was a n indestructible property of all living things. i. these wer e presumably bacteria.. THE SECOND HALF OF THE EIGHTEENTH CENTURY The advocates of the theory of sponta neous generation received staunch support as the eighteenth century entered its second half from the writings of Georges Leclerc. He regarded living matter as being composed of indestructible organic molecules which. sometimes survived boiling for half an hour.Origin and Migration of Worms 39 Other ideas were also canvassed. or "infusoria". In this work. whereas the other. Comte de Buffon (17017-1788) and John Turbeville Needha m (1713-1781). led to the development of the theory of heterogony. stomach and intestines. in the process o f spontaneous generation. swarmed with life a few days later. flukes and all other worms which are born in the liver. that these creatures were introduced into the human body and under the influence of heat and nutriment matured into entozoa. Nevertheless. Spallanzani found that there were two distinct classes of thes e microscopical creatures.e. The views of Buffon and Needham were attacked by the Italian abbott . Fo r example. Moreover. The discovery of microscopic animal s everywhere. despite being sealed . He concluded that animalcules may be carried into the infusions by the air and that this was the explanation of their supposed spontaneous generation 184. unable to penetrate the interior mould of the animal. ascarides. Spallanzani was criticized by the proponents . including in food a nd drinking water. subsequently. he took a portion of an almond germ and placed it in water in a phial closed with cork. a medical practitioner from Berlin. but even in the fetus within the body of the mother. Other investigators. and even in abortions . Some of the various erroneous ideas were expanded and magnified by many students of helminthology in the latter years of the century. and regarded it as an immature tapeworm which would develop into the adult broad tapeworm. Similarly. h e believed that he had discovered the free-living stages of Fasciola hepatica and Enterobius vermicularis. He acknowledged that many worms produced a vast number of eggs. Among the twelve "facts" which Bloch used to support this position were: .40 A History of Human Helminthology of spontaneous generation on the gr ound that he had "spoiled" the air by heating it. Schistocephalus solidus . Linnaeus. took the theory of heterogony and applied it to large r free-living creatures. Such was the interest in the origins of parasitic worms that the Royal Society of Copenhagen in 1780 set a prize essay on this subject. Others again seized hold of Vallisnieri's idea that entozoa were transmitted by the transplacental o r transmammary routes or by kissin g. There were opponents of such views.worms are sometimes located in very young animals. he mistook a planarian for the former and a free-living Rhabditis-like worm for the latter 117. not only in the young of animals. Germany. when swallowed.worms live in locations where other organisms are digested . while the second wa s taken by the Reverend Johann Goeze in Dudlinburg. as did Goeze who considered that egg s excreted in the faeces were lost for ever as far as the parasitic intestinal worm was concerned though they may serve as food for other animals 65. recently born animals. Both of thes e men argued for the spontaneous origin of parasitic worms. Pallas wrote that: It cannot be doubted that the eggs of Entozoa are scattered abroad and undergo various changes without loss of vitality. The discovery of the existence of eggs in many helminths was explained i n different ways. and that immediately they reach the body of a suitable . however. Diphyllobothrium latum . The first prize was won by Marcus Bloch. Some believed that eggs hatched out in the external world gave birth to free-living creatures and that these in turn were transformed into adult worms after their introduction into the intestines. The major evidence for this hypothesis was the assertion by a number of observers that they had found entozoa.most animals have their own peculiar parasitic worms 19 Bloch believed that worms destined to live in a particular location within a particular animal could not have arrived there by chance and that therefore they must have been generated spontaneously. Others would hav e none of this and considered them mere by-products. adduced the se same observations in favour of the theory of spontaneous generation.many worms which are never found in the gut occur in the interior parts of the animal without any passage to the exterior . He found a free-living tapeworm. Thus. the grea t classifier. however. Such concepts fitted nicel y with the theory of heterogony as developed by Linnaeus.worms die rapidly on removal from the host body . through a small wound into the abdominal cavity of a pup. In one of the duck's intestines I found 63 pieces of the tapeworm from the fish. he claimed to be able to find there small tapeworms and adduced this observation as in favour of his views 159. had nothing whatever to do with the ova h e administered. THE FIRST QUARTER OF THE NINETEENTH CENTURY Some of the foremost helminthologists of the early nineteenth century including Rudolphi and Bremser continued to proclaim the doctrine of spontaneou s generation. One month later. This trend seemed to be supported by the discovery that many cysts were verminous in nature (described in chapter 12) but were manifestly devoid of reproductive organs as were the microscopic organisms now known a s cercariae that had been discovered by OF Müller in 1773 and which h e classified as belonging to the "Infusoria" 136. through the medium of its food and drink. Helminthologists were content to point out the inadequacy of earlier attempts to explain the presence an d acquisition of entozoa and returned to the convenient theory of spontaneou s generation. now known as Dipylidium caninum. in general. I found only one tapeworm which was living. Rudophi. They had the same length and shape as in the before-mentioned seabirds. Abildgaard noticed that a cestode worm which lived in the intestine of the little fish known as a stickleback had no reproductive organs but bore certain resemblances to tapeworms that he had seen in mergan sers and other fish-eating birds. After another three days I killed the ducks and opened their intestines. his experiment was totally in error and the worms he found. Voices like his. led to an extremely important observation in 1790 by the Dane. 158 41 Pallas even attempted to prove hi s views by experiment. his hypothesis that worm s arose from eggs was correct. helminthology became separated from zoology and was treated as a distinct discipline. As thousands of animals were examined for the presence of parasites and as the number o f known entozoa became larger and larger. they grow into worms. Peter Christian Abildgaard. In 1781. were largely crying in the wilderness. Whereas. however. in retrospect. He wondered whether the worms in the fish cou ld be an immature form of the bird parasite so he decided to test this hypothesis: I collected a great number of stickleback fishes and for three days I fed those to two ducks. he introduced the small red eggs of the dog tapeworm. discovered the tapeworm now recognized . 1 This epochal observation was the first successful experiment designed t o elucidate the life cycle and transmission of an internal parasite. It became mere descriptiv e enumeration hardly concerned at all with the life-histories and development of the animals that were so carefully registered. The concept of heterogony. they were all living and more active and faster in their movements than those taken from the belly of the fishes. however. for example.Origin and Migration of Worms animal. In the other duck. All that slipped out by themselves had the appearance of. living.. Brendel26 and Doloeus 47..42 A History of Human Helminthology as Echinococcus granulosus and concluded that it arose from the intestina l epithelium172.. however. . coagulates forming a more solid mass which covers itself by an epidermis and then lives its own life. in whose journal Bojanu s published news of his discovery. which he believed provided the characteristic tail of the cercaria 149. Thus. but came from these peculiar.. Furthermore. he went on to add "one might lay a wager that these cercariae are the embryos o f distomes"152. the living unformed substance.cercariae. he cited the experiment of Schreiber 173 who fed a polecat for six weeks with milk containing eggs of various species of intestinal worms.. CL Nitzsch in Germany took up the study of th e organisms discovered by Müller and which Müller had placed in the genu s Cercaria.21 It caused much astonishment that cercariae were not derived from parent s resembling themselves. not a single worm was found. At the beginning of the winter of 1817-1818. at various places.. He was not able to put these pie ces of information together correctly. but in movement very indolent. Bremser considered it very improbable that eggs could b e transmitted through the medium of food. Oken.. in breaking through. Bremser wrote in 1819: The original formation of these worms. active movements which came from the enclosed winding animals. royal yellow worm s (subsequently called Redia by de Filippi 57).. yellow.. He called these sacs "royal yellow worms": When the Lymnaea [snails] were taken from the dish. Reim and others that intestinal worms had been found in the bowels of newbor n children and even in the fetus seemed to settle the point. He assumed that the pupal stage merely signified the termination of life 148 and concluded that a cercaria was a combination of a fluke with a vibrio. a momentous discovery wa s made by the German. critical observations continued to be made which would lead to a turning of the tide. in my opinion. under the microscope. water or air in the case of intestina l worms and believed that this was even more so in the case of hydatid cyst s which appeared to have no access to the external environment 25. takes place in the following way. ye t when it was killed. the acceptance by these authors of the claims by Kerckringiu s85. Subsequently the head is formed and ultimately the generative organs also appear. a very large number of royal.Some of the animals succeeded.In the yellow worm one saw. A part of the intestinal mucus. however. Nitzsch noticed that many of these cercariae transformed into a "pupa" or else "encysted" on foreign bodies and he also recognized a resem blance between the anterior part of the body of these organisms with flukes.25 Nevertheless. the matter was to lay for some years. Ludwig Bojanus. There. he noticed that s ome cercariae crept out of motile sacs in the viscera of the snails and concluded that they were probably generate d within them. In support of this thesis. cylindrical worms (Distomata?) were found in many of them. While dissecting some snails obtained from a fresh-water pond. With great perspicacity. finally. re marked that "observations of this kind make one dizzy"151. in commentating cynically on the improbable spontaneous generation of dioecious worms. the English surgeon. . Finland. Carl von Siebold. In 1827. although its relevance to the life cycles of certain parasitic worms was not immediately recognized. charged with animal particles in abundance. important observations of trematode s continued to be made which would eventually allow all the pieces in the puzzle to fall into place. one wit. by the spontaneous arrangement of its particles might produce an ox. showed that in the Salpae. Without this millions of males might be formed without a corresponding female. as will be described in the next section. 170 Likewise. a form of marine animal. wrote: two clots must consult together in order to determine into what they shall become transformed. A field of meadow gas. or the fermenting dunghill. in present-day Poland. A von Chamisso. and millions of females be condemned to live and die in single blessedness. and subsequently enter the body of some animal where they lose their eye-specks and become sexually mature. The next important link in the chain of evidence concerning these trematodes was furnished in 1835 by the German. CE von Baer confirmed Bojanus's observations and showed that cercariae developed from "germ granules" within the royal yellow worms or "germinating tubes" (rediae) 10. This observation was confirmed in the following year by von Nordmann in Helsinki. THE SECOND QUARTER OF THE NINETEENTH CENTURY Criticism of the theory of spontaneous generation began to gather apace.Origin and Migration of Worms 43 In the year after Bojanus published his observations. incidentally. Chamisso gave the name "Alternation of Generations" 34. had confirmed in 1829 Abildgaard's reports on larval tapeworms in fish and their maturation after ingestion by birds 41. there would be no end to the extension of the theory. To this phenomenon. free individuals and individuals bound together in chains alternated with one another in eac h successive generation. wrot e disparagingly: If we admit that a complex worm could be formed by spontaneous action of combination of animal particles. another importan t phenomenon was described. The German. This theme was to be taken up again and applied t o parasitic helminths nearly 25 years later by Steenstrup. Mehli s discovered that the eggs of certain flukes contained a larva which in shape and ciliation resembled some of the known "Infusoria" for he saw an infusorian-like embryo slip out of the eggs of worms then known as Monostomum flavum and Distomum hians 129. William Rhind. Several years later (1831). might be the matrix from whence springs the hog that feeds on it. who speculated that these embryos: always sojourn during their first life period in water. 48 Pari passu with comments like this. In his review of worms in 1829. 150 Similar observations were report ed in 1837 by Creplin 42 who. von Siebold made another important observation when he showed that some cercariae such as Cercaria echinata encysted in snails 175. and their fertility too striking. 54 He then went on to add: If this view be correct. for Steenstrup in 1842 to put all these disparat e observations together. Progress in the understanding of the life cycles of cestodes.. but he did not follow up the implications of this finding.54 Many of these ideas were formalized in the following year (1842) when the Dane. dissimilar to their parent. the propogation and development of animals through alternate generations: a peculiar form of fostering the young i n lower classes of animals 186. In all of them he found a common phenomenon whic h he summarized in the following terms: An animal bears young which are. Johannes Japetus Steenstrup. each one releasing from its interior a motile. or in their descendants.44 A History of Human Helminthology Von Siebold examined large numbers of the fluke. publ ished his seminal work entitled On the alternation of generations. he theorized that adult trematodes may produce eggs from whic h larvae hatch.. they died and disintegrated. Shortly afterwards. however. swim around to find an appropriate snail host. After recalling Abildgaard's experiments with fish worms and bird tapeworms and remarking on the great fertility of intestinal worms. their anatomy too complicated. divers e observations and proposed a unifying hypothesis to explain the various phenomenona. Von Siebold realized that these organisms were closely related to the rediae (or cercaria-sacs) that he had seen before in snails. that intestinal worms are the offspring of other similar worms. or.The life history of Entozoa must be considered as analogous on the whole to that of the parasitic larvae of ichneumon or bot flies but that each instance demands a special explanation on account of the complexities possibly introduced . penetrate th e tissues of the mollusc. Steenstrup brought together numerous. and finally trematodes.g. then die releasing rediae containing cercaria 174. Speculation about the life cycles of tapeworms and other helminths was undertaken by Eschricht. Although he was not able to actually witness the process. and remain. Steenstrup considered first coelenterates (medusae and clavifor m polyps).. the entozoon will spread by a kind of emigration. and especiall y nematodes. not to force the conviction upon us. he wrote in 1841: Their limitation to distinct species is too well ascertained. he noted the hatching of ciliated larvae (now called miracidia) from the eggs and watched the m swimming around in water. . Like Mehlis. then pelagic tunicates (Salpae).the various asexual parasites so frequently met with e. which lived in the orbital cavities of geese. It remained. Trichina spiralis must be regarded as immature forms retaining their primitive larval situations. Monostomum mutabile . In the same year (1835) that von Siebold correlated miracidia with rediae. he made an important discovery about tapeworm eggs when he found that the y contained an embryo furnished with six hooklets within them 174. but bring forth a new generation. After a wh ile. whose members either themselves. lagged somewhat behind these discoveries concerning trematodes. as will be detailed below. cylindrical body with two short latera l processes and furnished with a pharynx and simple gut. for example. . This is rather surprising as not only had Pallas and Goeze in the previous century recognized the relationship. lose their tails and become adult flukes.Origin and Migration of Worms return to the original form of the parent animal. This idea was contradicted by vo n Siebold who maintained that further developm ent could not take place until the encysted trematodes were transmitted to some other host. Von Siebold came to realize. This led him to the concept of "stray" worms . He conjectured that cystic worms were early stages in the development o f helminths that were unknown to him. At about the same time. He then modified this theory and began to move down the wrong path. He observed that in some of th e Trematoda. Dujardin in France in 1845 asserted that cystic worms were formed by the germs of tapeworms which. in supposing that the worm s matured in the body of the snail host. the latter generations remained within the earlier forms until they attained full development. whereas others forsook them sooner to becom e free-swimming then underwent a complete metamorphosis. so did the redia and cercariae derived from the miracidium of a fluke. and under the influence of an unusual dwelling-place. when they were devoured together with the snails by an animal 176. Moreover.177. that many encysted cercariae were located i n organisms which would never be consumed by another animal in which a n adult fluke would develop. Nevertheless. He was mistaken. He knew that Cercaria echinata encysted in snails so he extracted them at various inter vals after encystation and observed typical fluke-like forms. Likewise. Steenstrup's promulgation of the doctrine of "Alternation of Generations" put others on the right tr ack. He argued that they should no longer be classified as a separate group but he did not connect cystic worms wit h tapeworms. but a number of more contemporary authors including Nitzsch. contending that cystic worms were strayed larval tapeworms which becam e dropsically degenerated when they reached aberrant sites 181. who accepted spontaneous generation at first. developed abnormally to become "monstrous" cystic worms 49. 186 45 Thus. Dujardin. larval tapeworms 177. which was to bedevil his views on the relationship between cystic worms and tapeworms. considered that cercariae would never become adult worms once they had been shut in an "excreted prison" 49. however. he thought that the adult and larval forms of the worms must b e found in different animal hosts since the two forms rarely occurred together. however. von Siebold held the correc t view that cystic worms were simply undeveloped. Initially. Steenstru p conjectured that cercariae might penetrate into other animals. instead of going into the intestines of their natural hosts. Steenstrup failed to make the c orrect deductions with regard to cestodes. somehow arrived in the tissues. doomed to perish. Steenstrup believed that just as the polyp originating from the ovum of a medusa represented an alternate generation. FS Leuckart and F Müller had urged abandonment of this unnatural cleavage of cystic worms from tapeworms. von Siebold began to express similar convictions. Küchenmeister fed a large number of C. Friedrich Küchenmeister in Germany became interested in the problem o f cystic worms and tapeworms and began to experiment in order to solve th e problem. nor did they achieve such widespread recognition . I recovered 35 individual Taenia crasscipes from foxes that had been given approximately 40 Cysticercus pisiformis of rabbits 22. in order to achieve priority for my scientific observations and the further development of this subject. then the jointed adult tapeworm would mature. that between 18 March and 19 April 1851. he found dead worms in the gut thus giving credence to some earlier suggestions based upon epidemiological evidence that infection was acq uired by worms penetrating the skin59. h e provided no hard evidence to substantiate his views. Although there had been previous essays into experimentation i n helminthology. In 1851. He wrote in Gunsburg's Zeitschrift für klinische Medicin : Preliminary communication: I hereby give notice. fasciolaris to a cat and again succeeded in rearing . Abildgaard Creplin and Herbst. pisiformis to foxes which are natural predators of rabbits. THE THIRD QUARTER OF THE NINETEENTH CENTURY The second half of the nineteenth century opened with a flurry of speculation and activity concerning tapeworms and cystic wo rms. none had been as dramatic as Küchenmeister's were to prove. 15 and 8 days and 30 hours previously. Cysticercus pisiformis.92 Küchenmeister then gave C. It was at this point that a major wind of change blew upon the scene . In any case. of the rabbit and C. Küchenmeister began with two of the most easily accessible bladderworms. thus forming a cysticercus13. then the larva would develop but the hind part would become inflated and the head would sink into it. PJ van Beneden. fasciolaris of the mouse.93. On the other hand. Van Beneden was correct in deducing that bladderworms were larval tapeworms but was wrong in his belief that adult worms would develop directly from eggs when ingested by an appropriate host. then recovered many young tapeworms which he initially called Taenia crasscipes (= crassiceps = Taenia pisiformis)92. he postulated that if the egg found its way into the gut of an unsuitable host. With the realization at this time that the adult worms released large numbers of embryos.46 A History of Human Helminthology Little advance in understanding of nematodes was achieved during this period although some attention was paid to the mode o f transmission of Guinea worm. Forbes tried to transmit infection by administering orally t o two pups larvae that had been obtained from a human patient. Following the statements of Dujardin and von Siebold. theorized that the head of a tapeworm is produced from the eggs of a tapeworm and conjectured that if the egg reached the gut of a suitable animal host. In 1838. the Belgian. by investigators such as Pallas. there was conside rable speculation that transmission occurred via water. some of which had been successful. fasciolaris then reported the same phenomenon with Coenurus 178. with the exception of echinococci. Furthermore. In 1853. however. in the intestines 180. but a tapeworm larva provided with a temporary organ. Küchen meister obtained similar results with Cysticercus pisiformis . It was not until 1863. Dogs were killed after varying periods and von Siebold found innumerable small adul t tapeworms. but were tapeworm larvae that were an essential stage in the development and maturation of taenia: the larva (Cysticercus) is not a wandering strayed dropsical tapeworm nurse. He concluded that cystic worms were not strayed. he showed that when cysticerci were fed to an inappropriate host. These in tur n were fed to a healthy sheep on 25 July 1853. saturate d milk with echinococcal scolices.Origin and Migration of Worms 47 tapeworms that were rapidly approaching maturity 94. The first person to have demonstrated the generation of C. however. however. partl y because he changed his identification of the tapeworms that he reared in foxes several times. Von Siebold lost little time in repeating Küchenmeister's experiments. Such an experiment was first undertaken by Küchenmeister with the parasite he knew as Coenurus cerebralis (= Taenia multiceps). the cysticerci died and no development took place. he fed large numbers of Taenia solium eggs to a pig then slaughtered it four and a half months later at which . then fed it to a number of dogs. Wagner (1854) and others who used hydatid cysts obtained fro m sheep. dropsical tapeworms as portrayed by von Siebold. the nature of the cysticercus depending upon the host in which it developed 181. For a number of years von Siebold clung to his theory that cystic worms were degenerate. he successfully reare d tapeworms in dogs from Cysticercus tenuicollis and from Coenurus cerebralis of sheep96. He obtained cysts from sheep. it was also necessary to show thei r development from taeniid eggs. he also believed that. These observations also stimulated von Siebold to begin feeding exper iments with hydatid cysts in 1852. Von Siebold's experiments were repeated and his results confirmed by Küchenmeiste r (1853). Taenia serrata. straye d worms which would develop properly when transplanted to the correct site . tenuicollis and C. small coenuri were found on the surface of the brain 96. that Naunyn succeeded in rearing adult echinococci in the intestines of a dog fed with hydatid cys t material obtained from a human 145. To prove beyond all doubt that cystic worms were necessary steps in th e development of tapeworms. in the sense of Steenstrup's Alternation of Generations.179. cellulosae. all th e cystic worms were derived from on e species of tapeworm. In collaboration with Haubner. First he obtained coenuri from sheep then he administered them to a dog in order to obtain mature proglottids of the tapeworm. Shortly afterwards (1853). which were producing ova. cellulosae 99. Moreover. in fact. the shee p became vertiginous and when it was kill ed three days later. pisiformis and C. Sixteen days later. C. 95 Küchenmeister's first reports were received with some scepticism. I n 1852 he confirmed the metamorphoses of C. pigs and cattle. probably functioning as a reservoir of nourishment. was van Beneden. while in the other. At around the same period . Küchenmeister had an opportunity to repeat his original experimen t except that on this occasion he was able to infect the prisoner twice severa l months before execution. cellulosae. claimed to be able to do so. as indicated above. Leuckart's findings were soon confirmed by Mosler and many others. in collaboration with two medical colleag ues. On this occasion. bovis 111. von Stein. Tenebrio molitor. bovis to criminals in order to recover adult T. cellulosae to humans under the sentence of death. In the same year that Küchenmeister reported these observations (1855). solium segments79. Leuckart undertook a number of experiments in which he fed T. fasciolaris of mice (but which had been ignored). Others. He ther efore determined to examine the effects of administering C. Von Stein examined the development of a small blad der-worm in the larva of the meal-worm. the adult tapeworm is found. In late 1859 and early 1860. some form or other of an intermediary stag e occurs. success did not attend his efforts to generate the adult tapeworm w hen he fed cysticerci to dogs. he induced a convicted murderer (unknowingly) to ingest over 70 cysticerci during the several days prior t o execution. he found a number of small. he began to pass T. saginata from the intestines at autopsy. fasciolaris in the livers of mice after feeding these animals with eggs from T. No-one has ever gone to Küchen meister's lengths and fed C. immature tapeworms in the intestine of the condemned man 97. however. Forty eight hours after de ath. Although. and demonstrated that. the intermediate host. saginata segments to calves and eventually recovered the cysticercus known as C. but Küchenmeister (quite correctly) did not believe them. Aloys Humbert produced a patent infection in himself. In 1870. the largest of them being five feet in length 98. crassicollis from cats. together with an increasing m ass of experimental observations made it abundantly clear that development of these cestodes is divided between two kinds of animals. he recovered eleven tapeworms. A similar experiment with like result was undertaken by Leuckart in the following year 108.48 A History of Human Helminthology time he found a large number of cysticerci 14. John Oliver in India in some . whereas von Siebold believed that the scolex was formed first and that the tail then underwent hydropic degeneration 187. Küchenmeister was able to produce C. as Goeze had already proven in the case of C. that Leuckart produced hydatid cysts in suckling pigs after feeding them with ova of Taenia echinococcus (= Echinococcus granulosus )112. It took a little time to define the life cycle of the related human parasit e Taenia saginata. such as von Siebold and May. This. the definitive host. Another observation which helped finally to spell the lie to von Siebold' s concepts of "strayed tapeworms" flowed from t he studies in 1852 of the Prague zoologist. the caudal vesicle was formed first and then th e scolex developed within it. It was not until 1867. three months after consuming 13 C. In 1854. In late 1861 and early 1862. Leuckart was able to produce C. cellulosae by feeding Taenia solium eggs to pigs. In one. then Perroncito in Italy in 187 7 administered cysticerci to a subject who began to pass segments eight weeks later and from whom an adult worm over four metres long was recovered after treatment with anthelmintics 163.. they remained obdurate . 166 Nevertheless. by the method of feeding. were really the immature stages that excited so wide an interest.. He showed that when tailed. This was not an issue in the minds of these investigators. Despite all argument to the contrary. Indeed. bovis to three human subjects 153.It was not merely the proof that bladderworms which had for so long formed an impregnable fortress for the theory of spontaneous generation. Leuckart and Bertolus independently observed the hatching of larvae from D. The successes with these tapeworms did not similarly attend at this tim e attempts to elucidate the life cycle of the other tapeworm of major huma n importance.. Despite the mass of accumulated evidence. but by direct experiment. Knoch claimed in 1862 that there was direct transmission from one vertebrate host to another when he asserted that he had found diphyllobothria in the intestines of dogs after administration of ova whereas he had bee n unable to infect potential intermediate hosts 87. such experiments as wer e undertaken were positively misleading. claiming that all these experiments were "to o successful". Knoch.Origin and Migration of Worms 49 poorly-controlled experiments claimed to produce patent infections after feeding C. this was the last gasp of the sceptics and the views o f Küchenmeister and others became generally accepted. Nevertheless. and then undergo transformation into a vesicle. non-encyste d cercariae were administered orally to experimental animals they failed t o . but it was also the circumstance that Küchenmeister. which is so easy to control and repeat. Diphyllobothrium latum . and in particular Küchenmeister's con tribution. these studies inevitably had a critical effect on the tenability of the hypothesis of spontaneous generation. In reviewing all of these events. Trematodes did not evoke interest and activity comparable to that seen with the cestodes in the third quarter of the nineteenth century although severa l important contributions were made.. they were interested in defining the relationship between cystic worms an d tapeworms. Rather.did not discover it merely by chance. which engenders numerous scolices.. A number of workers includin g Schubart. there were still some recal citrants. Leuckart wrote a few years later: It was only with introduction of Helminthological experiment that a new path was opened to the field of knowledge. writing: we cannot believe that a microscopic embryo of a taenia enclosed in the intestines of a sheep can make for itself a passage up into the brain of the ruminant.116 It must be remarked. Pouchet and Verrier in 1862 attacked the whole concept of the cystic migration of tapeworms. latum eggs but their subsequent fate remained a mystery. George provide d important information in 1855. however.. La Valette de St. that the feeding experiments of Küchenmeister and others were not designed primarily to refute the doctrine of spontaneous generation55. Kölliker. cati to cats. Success was achieved. Enterobius vermicularis. however. Some desultory experiments were undertaken with Ascaris lumbricoides during this period. Unterberger in 1868 showed that Ascaris maculosa (= Ascaridia columbae) of the pigeon developed directly while Henry in 1873 demonstrated direct transmission of T. yet when certain encysted cerc ariae were ingested. the larvae escaped rapidly from the cyst walls and matured in the gut. however. particularly in view of a number of negative experiments: Mosler in 1860 failed to infect himself by swallowing eggs 134. All three of these investigators demonstrated the migration of newborn larvae. The larvae of this parasite had bee n discovered in 1835 and although von Siebold had suggested that they wer e intermediate stages awaiting tran sfer to another host. G Wagener in 1857 proved that the original hypothesis of von Sieb old was correct when he witnessed in snails the metamorphosis of the miracidium of Distoma cygnoides of the frog into a redia204. Virchow in 1859 discovered the adult T. Likewise. After a false start in which Leuckart concluded that Trichuris trichiura adults developed in pigs after they were fed trichinous flesh 109. Over the next several weeks. This finding was confirmed by Leuckart110. or a cat with Ascaris mystax (= Toxocara cati) ova112. spiralis in the intestines of a dog three and a half days after it was fed with trichinous meat 200-202. flavum became transformed into Monostomum flavum in finches and sparrows 196. The most significant advances were made with Trichinella spiralis. and the problem was not solved for anothe r decade. it was uncertain how this was achieved. lumbricoides eggs or a horse with Ascaris megacephala (= Parascaris equorum). Davaine thought it unlikely that an intermediate hos t was required for transmission. In November 1850. Cercaria echinifera was converted very rapidly in the intestine of warm-blooded animals int o Distoma echinfera while C. with such challenge infections with on e important nematode parasitic in humans. then shortly thereafter. Herbst reported a major discovery. Leuckart and three of his students swallowed a few dozen eggs of this worm that had been kept in a humidified incubator. however. he had tried without success to transmit infection to a cat b y inserting cysts subcutaneously. Thus.50 A History of Human Helminthology develop. he fed some trichinou s flesh obtained from a dead badger to three dogs then identified trichinellae in their muscles at variable intervals thereafter 75. Davaine faile d to infect a cow with A. A fe w years earlier. lumbricoides but did observe that larvae hatched from the eggs and were passed in the faeces when ova were fed to rats45. but this view was challenged by others. Investigations of the life cycles of nematodes during this period wer e sporadic and did not follow a common theme. a dog with Ascaris marginata (= Toxocara canis). they . Zenker identified the adult worms in th e small bowel of a human 212. while Leuckart in 1867 was unable t o infect a variety of animals with embryonated A. Nevertheless. This report was treated wit h much reservation. thus making the complete life cycle clear (se e chapter 22). In 1865. In 1851. The theory had gradually become intermingled with the problems of fermentation and putrefaction which were generally regarded as the result of some spontaneous chemical change in fermentible or putrescible matter. He therefore undertook an experiment in which he added fresh embryos to parasite-free Cyclops and noted that they were ingested by the crustaceans. 199 The other factor was the grad ual acceptance of the value of statistical methods in medicine and biology. which had previously seemed to be a point in favour of spontaneous generation.can be formed.that a new cell builds itself up out of any noncellular substance. in which he saw larvae similar to those of the Guinea worm. but the chance element in transmission. Statistics had been popularized by Laplace in hi s Philosophical Essay on Probability then was put to use by Pierre-Charle s Louis in his 1828 Researches on the Typhoid Affection or Fever . Fedchenko made use of Leuckart's observations and himself made a majo r discovery concerning the transmission of Dracunculus medinensis ... Thus.. Thus. Fedchenko noticed some small crustaceans. Cucullanus elegans. In 1869 . or that of the residue of the decomposition of animal and vegetable matter an infusorial animal. he wrote in 1859: Just as little as we can now admit that a Taenia can arise out of saburral [= foul] mucus. a doctor brought him a Guinea worm in a small bottle. In th e surrounding water. He was unable to complete the life cycle but speculated tha t infected Cyclops may be ingested by humans with release of the larvae in the gut and their subsequent development in the tissues 56.Origin and Migration of Worms 51 all recovered adult parasites from their faeces 112. Cyclops. a parasite of perch. The coup-de-grâce was finally delivered to the theory of spontaneou s generation during this period. Where the cell arises. A number of important experiments were made by Schulze. now appeared to be an example of a general biological law. The first was the development of histo pathology which climaxed in the cellular pathology of Virchow. the great fecundity of worms was now seen as a response to the low probability of continuity and survival of the species. there a cell must have previously existed. that no development of any kind begins de novo and consequently as to reject the theory of spontaneous generation. The effects of all these experiments on the doctrine of spontaneous gen eration of worms must also be viewed in the light of two other factors which had become apparent by this time.. An important landmark also occurred in 1865 when Leuckart reported that the embryos that had hatched from ova of the nematode. Further. Not only was this eventually to aid in the interpretati on of the results of experimentation.. as a general principle. Vircho w expounded the dictum "omnis cellula e cellula" (all cells out of cells).. S chwann.. Helmholtz. Th e corollary was that an organized being could not be formed out of formles s fluid. equally little are we disposed to concede. Schroeder and Ber- . the influence of air on fermentation an d putrefaction had been the subject of much discussion.. In July of that year. For many years.. developed in minute water crustaceans. he observed the moulting and development of these larvae within the crustaceans over the next several weeks.in pathology we can now go so far as to establish. however.52 A History of Human Helminthology nard. The next problem was to demonstrate that these germs were alive. These observations convinced him that fermentation and putrefaction were vital processes. the contents did not ferment. The flasks and their contents were then heated to boiling point for a long period. he had also altered in some way the contained air . who regarded fermentation as being "of the nature of death". that is that air carried germs. Like Spallanzani. Pasteur therefore set about proving the crux of his hypothesis. he did not believe that life could be generated from non-living matter. these were similar to the organisms that had already bee n observed in fermenting substances. Even though they were then left for months. Examen de la doctrine des générations spontanées which was published in 1861 162. In 1857 he isolated a ferment (since shown to be bacterial) that soured milk. He then took a series of flasks containing an infusion o f fermentable substances but in which the neck of each flask was very narrow and long. Meanwhile. hay. Pasteur had become interested in the problems of fermentation.165 Pouchet believed that spontaneous generation required the presence of a vital force coming from pre-existin g living matter. water and heat. First. The major criticism of Spallanzani's work had been that in boiling his sealed flasks. In 1858. fermentation became apparent within a few hours and organisms were demonstrated in it under the micro scope. more or less horizontal in orientation. thi s view compared starkly with that of Baron von Liebig. which he called heterogenesis. Pasteur believed that organisms associated with fermentatio n came from the air. When the neck was seve red. This he did by showing that sterile infusion s containing air which had been heated became infected if dust from the air was introduced into it. but the critical experiments were those of Louis Pasteur which wer e published in 1860 and 1861. the premier authority on the matter. The success of these experiments was the final turning point and marked the downfall of the doctrine of spontaneous generation. although a vociferous rear-guard actio n . These experiments were brought together in Pasteur's Mémoire sur les corpuscles organisés qui existent dans l'atmosphère. in the preface of which he explained how he had come to study the phenomenon: when by meditation it was evident to me that spontaneous generation was one of the means employed by nature for the reproduction of living things I applied myself to discover the methods by which this takes place. In 1859. he showed that germs or bodies resembling them existed in the air by filtering air through gun-cotton then examining the sedimen t microscopically. then he showed that yeasts or moulds on grapes were necessary for th e fermentation of sugar into alcohol in the making of wine. he published his book. and drawn out into an "s " shape. however. FA Pouchet had begun to present a series of papers to the Academy of Sciences in Paris in which he claimed to have proved th e existence of spontaneous gene ration. air. Hétérogonie. by experiments using flasks. the learned The New Sydenham's Society's Lexicon of Medicine and the Allied Sciences summarized the problem thus: This subject has attracted much attention of late years.. Pouchet in France. that animals can be gen erated spontaneously from non-living matter12. The results of one's experiments are the negative ones of his opponent. Bot h investigators were uncertain as to the subsequent course of events.191 and Leuckart in Germany113-115 independently worked out the life cycle of this parasite between 1879 and 1882... it may be said that no conclusive proof has been obtained of the occurrence of abiogenesis. 164 THE FINAL QUARTER OF THE NINETEENTH CENTURY It took some time for the dust to clear and for the controversy over spont aneous generation to be seen in perspective.On the whole. Rather. in a book of greater that one thousand pages published in 1872. Häckel in Germany and Bastian in this country have been its most prominent supporters.Origin and Migration of Worms 53 was fought for a number of years by a few workers including Pouchet. In reviewing the whole question in 1881. Charlton Bastian. the proponents of spontaneous generation gradually disappeared from view and the doctrine of spontaneous generation became abandoned by biologists.e... promulgated the doctrine o f "archebiosis". The first major success came with Fasciola hepatica when Thomas in England190. who a few years earlier had described in detail the anatomy of the Guinea worm. the opposition dies out and the rising generation becomes well-acquainted with the new truth from the start.Unfortunately. then were ingested... the evidence that one side regards as irrefutable is either entirely ignored or met with a direct denial by the other. He is a classi c example of the principle enunciated by Max Planck: A new scientific truth does not become accepted by way of convincing and enlightening the opposition. Häckel. Certainly. The latter in turn developed cercariae within them. The word "biogenesis" was coined by TH Huxley80 in 1870 to express the hypothesis that living matte r always arises by the agency of pre-existing living matter. encysted on grass. Perhaps the most extreme supporter of abiogenesis during this period was Bastian who. while the ter m "abiogenesis" was used for the opposite view. In a series of epidemiological studies and laboratory experiments. The matter was not settled until 1892 when Lutz showed that Fasciola cercariae were . i. and the English physician. no experimental helminthologists still supported th e concept.The most ingenious apparatus and modifications of experiments have been suggested by both sides. All their time and energy was devoted to elucidate the complex and mysterious life cycles of many parasitic worms. both authors discovered that miracidi a hatched from Fasciola eggs invaded Lymnaea snails and there metamorphosed into brood sacs or sporocysts in which rediae subsequentl y developed. postulating that either the snails containing cercariae were ingested or that cercaria e escaped from the molluscs.. Bastian continued the fight until his death in 1915. 167 In the event.. in a variety of fresh-water fish (pike. Calandruccio likewise i nfected a boy with Ascaris lumbricoides by administering embryonated ova to him. although that claim must be viewed with considerable circumspection in view of th e unusually short incubation period that he reported.23 . During this period. but how the fish became infected remained unsolved for another 35 years. Looss. but as is related in chapter 8. they showed that Hymenolepis diminuta developed in a variety of arthropod intermediate hosts 71. In 187 6. This was greeted with considerable scepticism. Leuckart reported that when he had fed ova of Trichuris affinis to a lamb and T. These findings with Fasciola led to an intensive search for a snail intermediate host for Schistosoma haematobium . migrate to the gut and mature119. ruff and burbot). H e then fed in 1881 these parasites to dogs and eventually recovered adult D. Strongyloides stercoralis 206. T. nothing was found and controversy continued until well into the next century as to whether an intermediate host was necessary. but several year s later he was able to prove his point as will be described in the next section. nor could they infect a dog by administering eggs orally69. perch. This was applied to the human parasite. Pieces were put into place partially or completely during this period for a number of nematodes. observations were made upon the life cycles of certain cestodes of lesser significance for humans. latum 22. . trichiura. then repeated the experimental process in humans 22. he was able to recover subsequently adult worms 112 then Railliet in 1884 reported a simila r phenomenon with dogs and T. Similar attempts were made to transmit hookwor m infection. Grassi found in 1887 tha t Hymenolepis nana could be transmitted directly from one definitive host to the next68. A far more important even t occurred when the German. Grassi and his colleagues failed to infect humans b y ingestion of either hookworm ova or larvae (presumably first-stage). the head of which resembled that of the broa d tapeworm. a feat which Wilms repeated in 1897 with th e similar parasite. crenatus eggs to pigs. working in Egypt reported in 1898 tha t infective larvae were able to penetrate the intact skin. Leichtenstern undertook feeding experiments and reported that he was able to infect humans by administering third-stag e hookworm larvae orally 102. In 1886. This experiment was also reported by Grassi67. however. the life cycle was completed 123. the results being reported by Grassi 67. In 1878. depressiusuculus. A partial solution to this problem was provided during this period by Max Braun in the eastern Baltic region. Grassi and Rovelli showed that Dipylidium caninum developed in fleas70.54 A History of Human Helminthology liberated from damaged or dead snails then en cysted on plant or other material. who had claimed a similar result in a few years earlier 66. Three years later. In 1889. In the same year. in 1886 when Calandruccio successfully infected himself after swallowing eggs. The second intermediate host was now clear. He found immature worms. He then demonstrated that when these cysts were fed to guinea pigs. The remaining cestode of major human importance of which the life cycle was obscure was Diphyllobothrium latum . He then examined the mosquitoes at daily intervals and found that the parasites metamorphosed in the insects' abdomen 128. Manson passed them on to George Low wh o prepared histological sections of the mouthparts and demonstrated th e infective larvae in the proboscis 122. hookworm ova were found in his faeces 71 days later. and with a stroke of luck selected mosquitoes as th e most likely candidate. He thereupon procured some mosquitoes and fed them upon his gardener who happened to have a microfilaraemia. a discovery of great significance was made in 1877 by th e Englishman. the exposed skin was excised and histo logical sections disclosed larvae in the dermis. great interest centred on Looss's claim of 1898 that hookworm larvae could p enetrate the intact skin. Almost immediately afterwards. These observations with hookworm were then applied to the similar parasite.Origin and Migration of Worms 55 Meanwhile. Manson's observations on the uptake and development of microfilariae in mosquitoe s were soon confirmed by Lewis and S ilva Araujo. He deduced that the most likely means of exit was via a blood-sucking insect. he applied filariform larvae to the skin of a thirteen year old boy one hour before he was due to have his leg amputated. Looss reported his findings in 1901 120 . Wuchereria bancrofti. As indicated in the preceding section. He was incorrect. I n order to prove his point. by allowing them to feed on an infected person then sent the specimens to Manson in London. The scene was set for hi s epochal discovery by the finding in 1872 by Lewis that the embryonic forms of the filarial parasite. but disbelief was still rampant. Manson was incredibly lucky in that he knew little about mosquitoes and happened by chance to use a species that wa s susceptible to infection. Thomas Bancroft in Australi a infected mosquitoes. releasing larvae which reached the human host via drinking water. a drop of culture fluid containing infective larvae was placed on his forearm. that had been reared in the laboratory and were free o f parasites. Immediately following removal of the leg. this report was greeted with considerable scepticism. working in China. in his surmise tha t mosquitoes flew off to stagnant water to deposit their eggs and there died . thus proving that the life cycle of this parasite could be completed in this manner 121. Strongyloides stercoralis. THE FIRST QUARTER OF THE TWENTIETH CENTURY At the turn of the nineteenth century. however. Manson puzzled about the fate of these larvae and tried to ascertai n their destiny. Jame s independently made similar observations 81. circulated in the periphera l blood. but it was not until 1900 that the final link in the chain was put in place. He therefore persuaded an hospita l attendant to allow himself to be infected ex perimentally. Patrick Manson. After ascertaining that the person was not infected already. Van Durme showed with histological studies i n 1901-2 that Strongyloides infective larvae were able to invade the skin o f . As is discussed in chapter 8. japonicum miracidia hatched from eggs. Fujinama and Nakamura showed by a series of experiments using cows that infection was acquired via the skin rather than by the ora l route 60. In 1909. He then fed a monkey on bananas contaminated with copepods that had been infected with guinea worm embryos five weeks earlier. although whether this was as a result of the experimental exposure or was acquired naturally cannot be determined with certainty193. investigators fell into one of two camps . They reported that they had collected snails of uncertain identity (subsequently shown to belong to the genus Oncomelania) from a roadside ditch. After a rapid series of experiments. Robert Leiper went to the Gold Coast (Ghana) to further in vestigate the life cycle of Dracunculus medinensis . Over ten years later. In 1913. found that they were free of trematode infections. Fülleborn took the final step in experiments with dogs and showed that larvae applied to the skin migrated through the lungs and then were able to develop into adult worms in the intestines 62. Leiper then turned his attention t o schistosomiasis in Egypt. His results wer e confirmed several years later by Kleine and then by Connal and his wife.61. observed their development through . In the light of these observations. he was able t o report in 1915 that he had infected Bulinus snails with miracidia derived from terminal-spined eggs (S. He found that development of microfilariae occurred in flies of the genus Chrysops 104 but he did not publish details of the developmental changes. Just over one year later. They observed that th e miracidia invaded the snails. developed into sporocysts then ultimatel y produced and released cercariae.those that favoure d direct transmission and those that believed that there must be an intermediate host.133. By analogy with Wuchereria bancrofti. Six months later. First. The events leading up to such infection were described by Miyair i and Suzuki in 1913. it seemed very likely that Loa loa was also transmitted by some form of biting insect. The answer came not from a study of Egyptian schistosomiasis. one of thes e persons developed a clinical infection. In 1905. Leiper journeyed to West Africa and fed many type s of arthropods on infected persons.56 A History of Human Helminthology guinea pigs50. then exposed them to S. In 1912. Turkhud in India gave a small number of infecte d Cyclops in water to five "volunteers". haematobium). Another question that burned in the minds of many helminthologists at this time concerned the manner of transmission of schistosomiasis. but from investigation of Schistosoma japonicum infection that had just been discovered in Japan. They then exposed the skins of mice t o cercariae released from naturally-infected snails and a few weeks late r recovered adult schistosomes from the portal veins of the infected mice 132.40. These results were then soon confirmed by Leiper and Atkinson 107 and by Yokogawa210. he found five immature Dracunculus in the tissues at post-morte m examination103. he repeated Fedchenko's experiments and examined the manner in which Cyclops were infected. th e latter pair of investigators providing considerable detail 39. It was not until 1917. In 1911 Yokogawa showed that trout were the second intermediate host of this infection 209. The mode in which fish became infected. now called Parafossarulus) naturally infected with several forms of cercariae. He then fed flesh of fish containing these cysts t o cats and recovered adult Clonorchis from the biliary system 88. In 1915. Miyairi . Fasciolopsis buski. Paragonimus. H e used these molluscs to infect fish then fed these fish to dogs and eventuall y found Clonorchis adults in the biliary tract 138. these details wer e published in 1922 144. 142 Nakagawa and Yokogawa all concluded that snails of the genus Melania (= Semisulcospira) were probably the first intermediate host. Similar success was achieved with Metagonimus yokogawai . In the following year. found that an immature. then developed into sporocysts. were elucidated. In 1911. Ando 4. Kobayashi's discovery stimulated his compatriot. Furthermore. Kobayashi . That this was so was proven by th e Japanese pathologist. Following his success with Clonorchis. while working i n Korea. however. Nakagawa turned his attention to the intestinal fluke. rediae an d cercariae in snails now known as Segmentina haemisphaerula 143. Muto.141. and at around th e 90 131 same time between 1917 and 1919.Origin and Migration of Worms 57 sporocysts to cercariae in the snails. Muto found that snails of the g enus Semisulcospira were the first intermediate host of this parasite 137. Kobayashi. H e then infected a dog and pigs with these encysted worms and succeeded i n recovering adult Fasciolopsis from the intestinal tract. he noted that the cercariae escaped from the snails and encysted on grass. In 1920. th e Japanese zoologist. Six years later. to search the local molluscs. Heterophyes heterophyes 154 but the first intermediate host remained obscure for a number . fishes. Independently. encysted fluke occurred commonly in certain freshwater fish in an area where clonorchiasis was endemic. clearly a second intermediate host. remained a mystery although Kobayashi suspected that snails may be involved. in 1918. however. He found a species of snail ( Bithynia. then infected mice percutaneously an d recovered adult worms 105. and the lung fluke. the life cycles of the liver fluke. mansoni) underwent development in snails of the genus Biomphalaria 106. he found that miracidia hatche d from Fasciolopsis eggs invaded. Attempts to solve thi s problem were confused initially by the uncertainty as to which form of encysted larva in the crab was really Paragonimus. Almost contemporaneously with these e vents. Nakagawa. Clonorchis. working in an area of Taiwan where paragonimiasis was endemic . became infected. he showed that miracidi a derived from lateral-spined ova (S. Onji and Nishio showed tha t certain fish were the second intermediate host of the fluke. Again the problem remained as to the manner in which crabs.89. In 1914 he found two sorts of en cysted trematodes in crabs of the genus Potamon. tha t Yokogawa proved which form of encysted larva was the precursor of the adult Paragonimus 211.139. He fed tissues from infected crabs to dogs and eventually recovered adul t Paragonimus from their lungs 140. amphibia and insects for the intermediate stages of Paragonimus. Both investigators came to this conclusion independently in June 1917. When the fish were killed s ubsequently. Janicki an d Rosen in Switzerland attempted to infect fish directly with larvae hatched from D. Rosen examined a number of potentia l primary intermediate hosts without success until he turned his attention t o copepods. Nicholl and Minchin found t hat Hymenolepis nana. Likewise. Dyce Sharp showed in 1927 that Mansonella perstans developed in Culicoides 51. he found plerocercoids in the musculature 171. In 1911. this worm has neve r been transmitted experimentally to humans. in addition to its direct cycle of transmission. the nature of the firs t intermediate host remained unknown. That these flies wer e indeed the vector was proven by Blacklock in Sierra Leone. Like most of the other filarial nematodes. Ciurea found that certain species of fish were the secon d intermediate host of Opisthorchis felineus 36.58 A History of Human Helminthology of years. Likewise. the missing link in the chain of transmission of the broad tapeworm. He found by a process of exclusion that all fish containing younger stages of the tapeworm ha d copepods in their gut 82. Edeson and his colleague s reported that they had induced a patent infection in a human with Brugia . When this failed. Rosen infecte d copepods by exposing them to tapeworm eggs then six weeks later placed trout in the aquarium.52. In order to complete the life cycle experimentally. Culicoides were found by Chardome and Peel in 1949 to be the intermediat e hosts of Mansonella streptocerca 35. latum eggs. he found oncospheres typical of D. In the body cavity of certain Cyclops. Buckley reported in 1933 that insects of the same genus were the vectors of Mansonella ozzardi 28. and in 1917 Robles in Guatemala had suggested on epidemiological grounds that blackflies of the genus Simulium may be involved but he offered no definitive evidence. latum 171. but again. THE REMAINDER OF THE TWENTIETH CENTURY The only helminth infection of major human importance in which the life cycle was still uncertain at the beginning of the seco nd quarter of the twentieth century was Onchocerca volvulus. The remainder of the century saw several small points in the life cycles of the important human parasites tidied up and observations made upon the lif e histories of a number of worms of lesser signifi cance. He reported i n 1926 that Onchocerca microfilaria were present in the gut of these insects and he traced their development into infective larvae which migrated into th e proboscis 17. During this period. With respect to nematodes of lesser importance for humans. In 1917. Diphyllobothrium latum . A number of investigators had studied a number of potential intermediate hosts without success.29.18. could also be acquired by ingestion of infecte d fleas147. was finally put into place. In 1960. Janicki examined the stomach contents o f species of fish that were known to transmit the infection. it is clear that almost no progress in an understanding of the nature of the origin and transmission of worms was achieved for most of recorde d history. viverrini were described by Wykoff and his colleagues in 1966 208. Cross and his colleagues reported in 1979 that they had transmitted successfully Wuchereria bancrofti to monkeys44. The latter infection was transmitted success fully to monkeys by Orihel and Pachecho in 1968157. like other living creatures. Even then. so that within three quarters of a century. Mackerras and Sandars described the molluscan inte rmediate host of Angiostrongylus cantonensis in 1955124 while Morera and Ash in 1971 described the slug vector of Angiostrongylus costaricensis. Infection with Capillaria philippinensis was shown to be by ingestion of infected fish by Cross and his colleagues in 1972 43. while Krull and Mapes later found that meta cercariae developed in ants 91. In 1934. but perhaps even more important was the popularization by Küchenmeister beginning in 1851 of the use of experimental method i n solving these problems. A veritable explosion of information and discovery then followed. A landmark in theoretical understanding was the publication of the theory of "Alternation of Generations" by Steenstrup in 1842. OVERVIEW In retrospect. the life cycles of all the major human helminth infections were understood. malayi 53. The details of the first and second intermediate hosts of Gnathostoma spinigerum were described by Prommas and Daengsvang in in 1936 168. Today's helminthologists ar e attempting to apply all of these achievements to the control of these ubiquitous . With respect to trematodes of lesser human significance. In 1933. Tubangui and Pasco identified the snail intermediate hosts of Echinostoma ilocanum 192. Cameron in 1931 showed that certain snails were the intermediate host o f Dicrocoelium dendriticum 32. Concerning cestodes of less importance for huma ns. Stunkard showed in 1940 that mites were the vector of Bertiella studeri 188. Four years earlier. This coincided with elucidation of the means by which parasiti c helminths were transferred from one host to another. were produced from gametes.Origin and Migration of Worms 59 pahangi although they had failed to achieve this result with B. Likewise. it took nearly 200 years for the issue to be settled finally with general acceptance that worms. Vogel showed tha t snails of the genus Bithynia were the first intermediate host of Opisthorchis felineus 203. Asada in 192 8 discovered the snail first intermediate host of Heterophyes heterophyes 7. The first and second intermediate hosts of O. Spontaneous generation of helminths seemed a perfectly respectabl e explanation and only began to be seriously questioned in the late seventeent h century. Orihel and Moore had transmitted Loa loa to two species of subhuma n primates156. 1793.60 A History of Human Helminthology parasites and prevention of infections in human populations. von BAELLSTADT A (ALBERTUS MAGNUS). Partly translated in 55 . Loeb Classical Library . ABILDGAARD PC. 1926 19. Partly translated in 86 9.. H van Kroonevelt. 1926 18. London. London. German translation in Schriften der Naturforschen der Gesellschaft.. ALDROVANDI U. 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Handwörterbuch der Physiologie mit Rücksicht au f physiologische Pathologie.. Om Fortplantning og Udvikling gjennem vexlende Generation s Raekker en saeregen Form for Opfostringen i de lavere Dyreklasser. SPALLANZANI L. pp 88. pp 49. von SIEBOLD CT. Also. von SIEBOLD CT. Buch 4. 1881 191. Über die Band. Parasiten. TUBANGUI MA. 1835 175. On the alternation of generations. 1908). of the joynted worm. 1669. Th e Sydenham Society. PASCO A. 2: 650-676. are remarked. von SIEBOLD CT. TURKHUD TA. pp 580. Upuscoli de fisica animale e vegetabile. 1940 189. Archiv für Naturgeschichte 9: 300-335. series 3. Historia insectorum generalis etc. Cited in 112 183. Archiv für Naturgeschichte 1: 45-84 . 1755. 1933 193. Saggio de osservazione microscopiche concernanti il sistema della generazione de' Signori de Needham e Buffon. von SIEBOLD CT. Expérience sur la transformation des vers vésiculaires ou cysticerques in taenia. Bertiella studeri. revised and improved by notes from Reamur and others.. 1914 194. revise d edition. Report of the Bombay Bacteriological Laboratory for the year 1913 . 17: 377-381. its . W Engelmann. or the history of insects. American Journal of Tropical Medicine 20: 305-333. Translated in Quarterl y Journal of Microscopical Science 2: 255-263. 1844 178. Ueber die Verwan dlung der Echinococcus-brut in Taenien. THOMAS A P. von SIEBOLD CT. translated by G Busk from the German version of CH Lorenzen. von SIEBOLD CT.. 1882.illustrated with coppe r plates. Zeitschrift für wissenschaftliche Zoologie 4: 400-408. CA Reitzel .. Ueber die Verwa ndlung des Cysticercus pisiformis in Taenia serrata. 1960 184. Beiträge zur Entwickelungsgeschichte der Eingeweidewürmer. In. presented by WG Liston. pp 115. Also. Philippine Journal of Science 51: 581-603. translated from the Dutch and Latin original edition by T Flloyd. 1758 190. M van Dreunan. editor). R Wagner (Editor).with the life of the author by H Boerhaave. L Pasquati. Zeitschrift für wissenschaftliche Zoologie 4: 196-214. The life history of the human intestinal fluke.. Abstracted in British Medical Journal ii: 1001-1002. SCHREIBER. 1857 182. 1618 186. pp 88. Die Physiologie als Erfahrungswissenschaft (KF Burdach. pp 14-16. Partly translated in 84 181. with an introduction on the origin of intestinal worms. Modena. STUNKARD HW. SPIGELIUS A. bound with volume 2 of F Küchenmeister's "Manual of parasites". 1853.und Blasenwürmer nebst einer Einleitung über di e Entstehung der Eingeweidewürmer. 1854 180. pp 132. The morphology and life history of the cestode. by J Hill. 1837 176. The Book of nature. wherein a great many mistakes of former writers concerning it. 1882 192. 1853. TYSON E. Zur Entwicklungsgechichte der Helminthen. 1845 187.. Leipzig. Second report of experiments on the development of the liver fluk e (Fasciola hepatica).68 A History of Human Helminthology 173. or. SWAMMERDAM J. 1766 185. or a discourse read before the Royal Society. Helminthologische Beiträge. 1843 177. 1852 179. Patavii. von SIEBOLD CT. In. Cited in 25 174. Journal of the Royal Agricultural Society of England 18: 439-455. translated by T H Huxley. London. Euparyphium ilocanum (Garrison. London. Abelard-Schuman. Journal of the Royal Agricultural Society of England 17: 1-28. The Ray Society. A history of biology to about the year 1900. Bericht über die Leistungen im Gebiete der Helminthologie während des Jahres 1842. A Hirschwald. The Lumbricus Latus (Abstract). 175. 196. Lutetia e Parisiorum. Philosophical Transactions of th e Royal Society 13: 113-144. Helmintholgische Notizen. Press . 1585. Berlin. pp 1696. 203. Zoologica 33: 1-103. Original edition c. Memoirs of the Philosphical Transactions of the Royal Society pp 122-130. Schistosomiasis: the evolution of a medical literature. 1855 VALLISNERIUS (VALLISNIERI) A. 1973 WILMS. 1934 WAGENER H. 1552 WYKOFF DE. 1859 VIRCHOW R.T. 1860 . pp 1307. pp 112.the life cycle and comparison with O. In. as a difficulty against the doctrine of univocal generation. Schmidt's Jahrbücher der in-und ausländischen gesammten Medicin 256: 272. De differentiis animalium. Opera omnia. Futterungsversuch mit Trichina spiralis. De lumbricus et ascaridibus. Translated in 84 . Berlin. 198. Taiwan Igakkai Zasshi 149: 178-183. Symbolae ad trematodorum evolutionis historiam . 1860 VIRCHOW R. (Paragonimus ringeri . Opera fisico-mediche stampate e manoscritte . 1917. Basileae. Abstracted in British and Foreign Medico-Chirurgical Review 26 : 515-516. Abstracted in 205 YOKOGAWA S. Journal of Parasitology 51: 207-214. pp 440. 209. In Japanese. especially on its intermediat e host. GEORGE A. pp 38.. 1857 WARREN K S. (Schistosoma japonicum in Formosa. 1300. Recherches sur le développement de la trichina spiralis (Ce ver devien t adulte dans l'intestin du chien).) Taiwan Igakukai Zasshi No. 212.I. Anchylostoma duodenale und Angullula intestinalis . 199. Comptes Rendus Hebdomadaires des Séances d e l'Académie des Sciences 49: 660-662. translated from th e second edition by F Chance. Raccolte da Antonio suo figliuolo.). Study of stages from the crab and points o f difference distinguishing it from similar cysts occurring there. 1965 YOKOGAWA S. Ueber die trichinen-Krankheit des Menschen. Beiträge zur Entwickelungs-Geschichte der Eingeweidewürmer . 205. (A new parasite involving trout as its intermediate host and its ne w generic name.Origin and Migration of Worms 69 195. natural history from more exact observations is attempted.) nebst Bemerkungen über Systematick und Epidemiologie. 1859. 1915. three volumes. 204.) Okayama Igakkai Zasshi No. Cambridge. Archiv für pathologische Anatomie und Physiologie und für klinische Medicin (Virchow) 18 : 330-345. 1683 TYSON E. Naturkundige Verhandelingen van de Hollandsche Maatschapij der Weteschappen t e Haarlem. 1858. Partly translated in 37 VILLANOVANUS (de VILLENEUVE) A. S Coleti. 1733 . 1897 WOTTON E. 202. Opisthorchis viverrini in Thailand . JUTTIJUDATA P. 210. Cited in 37 VIRCHOW R. 206. 207. Venezia. London. and the whole urged. 3. J Churchill. 1860. 201. In Japanese YOKOGAWA S. Mass. WINN MM. Abstract of 194 la VALETTE de ST. 1918 ZENKER FA. Archiv für pathologisch e Anatomie und Physiologie und für klinische Medicin (Virchow) 18: 561-572. 197. HARINASUTA C. Die Cellularpathologie in ihrer Begründung auf physiologische un d pathologische Gewebelehre. 211. 1860 VOGEL H. Deutsche Klinik 11: 430. M. Ueber Trichina spiralis. In Japanese. Cellula r pathology as based upon physiological and pathological histology. pp 298-307. 279. Abstracted in Tropical Diseases Bulletin 12 : 173-174. Edoardi Wuottoni Oxoniensis. 208. felineus. pp 511. 200. Der Entwicklungszyklus von Opisthorchis felineus (Riv. 1912. 1859 VIRCHOW R. sealed infusions were sterile and concluded that "animalcules" were carried in by the air The Royal Academy of Science in Copenhagen set a prize essay on "The origins of parasitic worms". Pallas injected Dipylidium caninum eggs into the abdominal cavity of a dog and concluded erroneously that they developed into adult worms Linnaeus believed incorrectly that certain specific. He believed that he had observed the eggs of tapeworms Buffon and Needham defended staunchly the theory of spontaneous generation Spallanzani showed that heated. both of whom believed in spontaneous generation. multiceps from Coenurus cerebralis 1673 1698 1700 1750+ 1766 1780 1781 1787 1790 c. however.1800 1810-19 1817 1818 1819 1831 1835 1835 1837 1842 1851 1851 1852 1853 . First and second prizes were won by Bloch and Goeze . and discerned the encystation of cercariae Bojanus discovered that cercariae w ere generated within organisms (rediae) within snails Chamisso described the alternation of generations of marine animals belonging to the family. that intestinal worms may be generated spontaneously Leeuwenhoek began to publish the results of his observations using a microscope of the microbiological world Bidloo discovered eggs of Fasciola Andry in his textbook declared that all parasitic worms were bred by means of a "seed" introduced from the external envi ronment.1. was correct Abildgaard fed stickleback fis h containing immature cestodes to a duck and found them living in the gut three days later The discovery that many cysts were verminous in nature yet had no reproductive organs seemed to support the idea of spontaneous generation Rudolphi (1810) and Bremser (1819) in their textbooks of helmintholog y continued to support the theory of spontaneous generation Nitzsch noticed the resemblance between cercariae and flukes. The principle. immature free-living helminths that were ingested in food and water. parasitic worms develope d from morphologically similar. Salpae Mehlis observed larvae (miracidia) hatch from fluke eggs von Siebold observed rediae released from disintegrating miracidia in water von Siebold discovered larvae with hooklets within tapeworm eggs von Siebold found that certain cercariae encysted inside snails Steenstrup published his book on the "Alternation of Generations" in which h e proposed a unifying hypothesis to explain the life cycles of certain trematodes and other organisms Herbst found Trichinella spiralis larvae in dog muscles after feeding them with infected badger flesh Küchenmeister fed Cysticercus pisiformis of the rabbit to foxes and recovere d adult tapeworms (Taenia pisiformis ) from the gut Küchenmeister gave Cysticercus fasciolaris of mice to a cat and recovered adult tapeworms (Taenia taeniaeformis ) Küchenmeister reared adult tapeworms in dogs fed with cystic worms from sheep: Taenia hydatigera from Cysticercus tenuicollis and T. however. Landmarks in the understanding of the origin and transmission of worms ___________________________________________________________________ BC 1668 The spontaneous generation of certain animals was generally accepted Redi showed by experiment that maggots in rotten meat developed not b y spontaneous generation but from eggs deposited by flies. He conceded.70 A History of Human Helminthology Table 2. respectively. George showed that certain encysted cercariae but no t non-encysted cercariae developed into adult flukes when ingested by birds o r animals Wagener witnessed the metamorphosis of Distoma cygnoides miracidia into rediae in snails Pasteur showed that a bacterial ferment soured milk and that yeasts or mould s were necessary for the making of wine from grapes Virchow discovered adult Trichinella spiralis in the gut of a dog after feeding it with trichinous meat Zenker discovered adult Trichinella spiralis in the bowel at the post-morte m examination of a young woman who had died of a typhoidal illness after recently eating trichinous pork Küchenmeister repeated his experime nt on a condemned murderer.5 m long Pasteur showed that air contained bacteria which caused putrefaction in steril e infusions Leuckart fed Taenia saginata proglottids to calves and generated Cysticercus bovis Leuckart and his students swallo wed Enterobius vermicularis eggs and developed patent infections Leuckart generated hydatid cysts in pigs after feeding them with Echinococcus granulosus ova Oliver may have produced a patent Taenia saginata infection in a human afte r feeding Cysticercus bovis to a man Fedchenko reported that Dracunculus medinensis larvae developed with the body of Cyclops (crustacean) Perroncito recovered an adult Taenia saginata from a human 4 months afte r ingestion of Cysticercus bovis Manson discovered that Wuchereria bancrofti microfilariae metamorphosed i n certain mosquitoes Thomas and Leuckart independently discovered that Lymnaea snails were the intermediate hosts of Fasciola hepatica Braun showed that certain freshwater fish were the second intermediate hosts of Diphyllobothrium latum by feeding infected fish to dogs and humans the n recovering adult worms Calandruccio produced a patent infection with Trichuris trichiura in himself after swallowing eggs Leichtenstern produced patent infections with hookworm in humans afte r administering infective larvae orally Grassi showed that Hymenolepis nana could be transmitted directly from on e definitive host to another Grassi and Rovelli reported that Dipylidium caninum larvae developed in fleas Grassi and Rovelli showed that Hymenolepis diminuta developed in a variety of arthropod intermediate hosts .Origin and Migration of Worms 1853 1854 1855 1855 1855 71 1857 1857+ 1859 1860 1860 1861 1862 1865 1867 1870 1870 1877 1877 1881 1881-3 1886 1886 1887 1889 1892 von Siebold discovered Echinococcus granulosus adult worms in the intestines of dogs after feeding hydatid cysts to them van Beneden generated Cysticercus cellulosae by feeding Taenia solium eggs to pigs Küchenmeister reported the recovery of immature Taenia solium after feeding Cysticercus cellulosae shortly before execution to a condemned murderer Humbert ingested Cycsticercus cellulosae and three months later began to pas s Taenia solium proglottids in his stools la Valette de St. The incubation period was several months and this time he recovered Taenia solium tapeworms up to 1. and recovered adult worms from mice infected percutaneously with cercariae released from these snails One out of five persons given infected Cyclops to drink by Turkhud develope d dracunculiasis one year later Fülleborn showed that Strongyloides stercoralis larvae applied to the ski n developed into adult worms in the gut of dogs Nakagawa showed that crabs of the genus Potamon were the second intermediate hosts of Paragonimus westermani Onji and Nishio found that certain fishes were the second intermediate hosts o f Heterophyes heterophyes Leiper and colleagues showed that miracidia from terminal-spined egg s (Schistosoma haematobium) developed in Bulinus snails. Nakagawa and Y okogawa all concluded independently that Melania (= Semisulcospira) snails were the first intermediate hosts o f Paragonimus Muto showed that Bithynia (= Parafossarulus) snails were the primar y intermediate hosts of C. described the intermediate stages.72 1892 1897 1898 1900 1901 1901-2 1907 1909 1911 1911 1911 1913 1913 A History of Human Helminthology Lutz fed Fasciola cysts to guinea pigs then recovered adult flukes Wilms infected a human by administering Strongyloides stercoralis larvae orally Looss first claimed that hookworm infective larvae penetrated the intact skin Low reported thatWuchereria bancrofti infective larvae were found in th e mouthparts of mosquitoes that had been filariated by Thomas Bancroft Looss showed by histological examination of an amputated leg that hookwor m larvae applied before amputation penetrated the skin van Durme showed that Strongyloides larvae penetrated the skin Leiper recovered immature Dracunculus medinensis from a monkey 6 month s after feeding it water containing infected Cyclops Fujinami and Nakamura demonstrated that Schistosoma japonicum infection in cows was acquired via the skin Looss reported the development of a patent hookworm infection 71 days afte r percutaneous infection of a human Yokogawa discovered that trout were the second intermediate hosts o f Metagonimus yokogawai Kobayashi recovered adult Clonorchis sinensis from the biliary system of cat s after feeding them with fish infected with certain encysted. mansoni) Muto reported that Semisulcospira snails were the first intermediate hosts o f Metagonimus Ciurea discovered that certain fishes were the second intermediate hosts o f Opisthorchis felineus Janicki and Rosen discovered that certain crustaceans ( Cyclops) were the first intermediate hosts of Diphyllobothrium latum Ando. then recovered adult worms after infecting mic e percutaneously with cercariae obtained from these mice Leiper proved that miracidia derived from lateral-spined eggs developed i n Biomphalaria snails and were a different species ( S. sinensis Nakagawa reported that Segmentina snails were the first intermediate hosts o f Fasciolopsis buski Nakagawa showed that Fasciolopsis cercariae escaped from the snails an d encysted on grass. then fed them to dogs and recovered adult worms Connal and Connal provided detailed descriptions of the development of Loa loa 1913 1914 1914 1915 1915 1916 1917 1917 1917 1917-19 1918 1921 1922 1922 . Miyairi. immature flukes Leiper reported that tabanid flies ( Chrysops) were the vectors of Loa loa Miyairi and Suzuki discovered that Oncomelania snails were the intermediat e hosts of Schistosoma japonicum . Kobayashi. described the larval stages of the parasite. malayi Morera and Ash described the slug vector of Angiostrongylus costaricensis Cross and his colleagues found that Capillaria philippinensis infection was acquired by ingesting infected fish Orihel and Moore transmitted Loa loa to subhuman primates Cross and his colleagues successfully infected monkeys with Wuchereria bancrofti ___________________________________________________________________ .Origin and Migration of Worms 1926 1927 1928 1931 1933 1934 1936 1949 1952 1953 1955 1966 1968 1971 1972 1975 1979 73 in Chrysops Blacklock discovered that Simulium blackflies were the vectors of Onchocerca volvulus Dyce Sharp showed that Culicoides midges were the vectors of Mansonella perstans Asada described the snail intermediate host of Heterophyes heterophyes Cameron observed that certain snails were intermediate hosts of Dicrocoelium dendriticum Buckley found that Culicoides was the vector of Mansonella ozzardi Vogel found that Bithynia snails were the first intermediate hosts of Opisthorchis felineus Prommas and Daengsvang described the first and second intermediate hosts o f Gnathostoma spinigerum Chardome and Peel showed that Culicoides was the vector of Mansonella streptocerca Krull and Mapes showed that Dicrocoelium dendriticum larvae encysted in certain ants Edeson and his colleagues infected a human with Brugia pahangi using Mansonia mosquitoes Mackerras and Sandars reported that slugs were the intermediate hosts o f Angiostrongylus cantonensis Wykoff and colleagues described the first and second intermediate hosts o f Opisthorchis viverrini Orihel and Pachecho produced patent infections in monkeys with B. 74 A History of Human Helminthology . for example. Guinea worm (Dracunculus medinensis) was found in certain restricted localities but its verminous nature was a matter of some controversy. major traditional remedies are reviewed in relation to different regions of the globe. The Egyptian 75 . For convenience.e. Nevertheless. In addition. the pomegranate (Punica granatum) was utilized in countries ranging from Egypt to China. castor oil and senna were recommended as purgatives and anthelmintics were often administered together with honey. the same or related plants were used over wide geographical areas. Most attention. in some instances. sweet beer or dates126.1500 BC). only a very small number of parasitic helminths were known during most of recorded history. Herbal products that were believed to have specific vermicidal or vermifugal properties were often combined with purgatives (to flush the worms out) and various sweeteners or diluents. Thus. the common roundworm (Ascaris lumbricoides) and the pinworm or threadworm (Enterobius vermicularis). As discussed elsewhere in this book. Plants were the major therapeutic sources. The development of herbal products depended upon the local botanical flora with the result that different remedies tended to develop in different parts of the world.Chapter 3 THE DISCOVERY AND DEVELOPMENT OF ANTHELMINTICS TRADITIONAL REMEDIES Men have undoubtedly tried to rid themselves of worms infecting their bodies for almost as long as they have recognized them. therefore. In the Egyptian Papyrus Ebers (c. the coincident. i. THE MEDITERRANEAN REGION Many different anthelmintics were used in the countries abutting the Mediterranean Sea in the centuries before the birth of Christ. These were certain visible worms that enjoyed a wide geographical distribution and were extruded from time to time from the gastrointestinal tract. While it is true that certain preparations did have some therapeutic efficacy. however. tapeworm proglottids or segments (Taenia and Diphyllobothrium species). was paid to the common intestinal worms. spontaneous passage of senescent worms often led to anthelmintic properties being ascribed erroneously to many concoctions. garlic. Pomegranate The roots or bark of the pomegranate (Punica granatum) have been used as an anthelmintic for millenia. there should be given as draughts. coriander seeds.76 A History of Human Helminthology Papyrus Ebers (c. mulberry. was isolated as the active principle26 and pomegranate decoctions remained a standard remedy until well into the twentieth century.. pomegranate bark was little valued in northern Europe until the beginning of the nineteenth century when the Englishman. as well as extracts of Artemisia.126 Pomegranate continued to be popular with the physicians of ancient Greece and Rome for the treatment of both roundworm and tapeworm infections and was still being recommended around 1. to which may be added. is strained and taken in one day. Nevertheless. or mint in the same of a decoction of worm-wood or hyssop in hydromel or cress-seeds pounded up in vinegar. At three hours interval. Male fern (filix mas. anise seed. acacia gum. let him take two further draughts. Alternatively. fennel.650 BC) in Assyria refer to mint. spearmint and male fern root found their way into the materia medica of ancient Greece and Rome. and drink it on an empty stomach. Celsus (c. after pounding. turpentine. Avicenna6. scammony seed. otherwise known as filix mas or oleoresin of aspidium. then on going to stool. colocynth and senna as well as specific vermifuges such as pomegranate 126. Thus. crush them and boil them in a litre and a half of water down to one-third. myrrh. Buchanan. or of mulberry bark. both the same remedies may be given and some milder ones. a decoction of lupins. or administer into the lower bowel a clyster of olive oil.28 Many of these drugs maintained their popularity over the next two thousand years. Extraordinarily complicated combinations of drugs and directions for their administration were evolved. Again. remains during the night in the dew. onion. pepper.1500 BC) mentions various purgatives such as castor oil. water 10 ro. olive oil. is derived . Perhaps the earliest record is in the Egyptian Papyrus Ebers: to kill roundworm: root of pomegranate 5 ro (1 ro = 15 ml). for the roundworms.. Clay tablets found in the library of Asur-bani-pal (c. introduced it from the the East Indies. pelleterine. oleoresin of Aspidium) Male fern. sit over a basin of hot water. then on the next day take a handful of fine pomegranate roots.000 AD by the Arabian.. such as pounded-up seeds of nettles or of cabbage or of cummin in water. but with the addition of half a pint of sea water or strong brine. to this add a little soda.. These agents. The alkaloid. or a little scammony. either hyssop or a vinegar cupful of pepper. It is also of service either to eat lupin or garlic. colocynth.25 AD) wrote: For the flat worms. on one day let him eat a quantity of garlic and vomit. pomegranate and cassia as anthelmintics79. The active principle is santonin. The major anthelmintic constituent is filicic acid (= filicin)26. .285 BC) who wrote: Of male fern. leaving a dry. It has no seed nor juice. It was mentioned by the Roman. scammony and gamboge after two hours. Semen-contra-vermes was added to the British Pharmacopoeia in 1863. Three drachms of the pulverized root in four ounces of infusion were administered followed by a bolus of calomel. Pliny (23-79 AD). The general practice was to collect rhizomes of the plant in autumn. it was most effective against Ascaris. in the first century AD as being indicated for the treatment of ascariasis and enterobiasis 50. Male fern was added to the British Pharmacopoeia in 1863. Male fern remained popular in the treatment of tapeworm infections until more effective and less toxic drugs became available in the middle of the twentieth century.000 francs for the formula. then soak them in ether for 48 hours. These plants are spread widely throughout the northern hemisphere. When vomiting occurred. a sesquiterpene lactone27. The French king. and less efficacious against Enterobius. a number of phloroglucinol compounds have been isolated as active principles. It consists of the dried. moderately active against tapeworms. cina. an ounce of magnesium sulphate in warm water was then drunk. and they say it is ripe for cutting in the autumn. It expels the flat worm. This was then filtered out. It remained popular for centuries and was mentioned by Avicenna (980-1036) 6. the remedy was repeated and strong coffee was given to prevent sickness. One classic example of its use was as the major constituent of Madame Nouffer's "Tapeworm Cure" in the late eighteenth century.Anthelmintics 77 from the powdered rhizomes of Dryoptera filix mas. no part but the root is useful and it has a sweet astringent taste. Louis XVI. oily residue. oil of aspidium. especially A. was somewhat peeved to find this in 1776 after he had handed over 18. Dioscurides Anazarbeus. Filix mas has maintained its popularity in one form or another for centuries. unexpanded flower heads obtained from several species of the genus Artemisia (= Santonica). free them from roots and dead parts. If the worm was not fully expelled in four hours. recommended powdered root of male fern as an anthelmintic24. According to Davaine in 186046. Madame Nouffer's technique was described by Davaine46. The drug was abandoned in the early twentieth century when more effective and less toxic agents became available. The efficacy of this extract in the treatment of tapeworm infections was recorded long ago by the Greek. Theophrastus of Eresus (370-c.165 Likewise. the Roman. Beginning with the work of Boehm in 1897 14 . Semen-contra-vermes (Santonin) Semen-contra-vermes (semen against worms) is so-named because of its fancied resemblance to semen. however. Modern studies have given conflicting reports on the effectiveness of pyrethrins against cestodes26 and there is some evidence that they are partially active against intestinal nematodes27. was kousso. Rochet d'Héricourt brought enough drug for 40. Their use was praised by Paracelsus (1493-1541) 127 and tin filings were commonly prescribed until the first half of the nineteenth century. AFRICA Anthelmintics used traditionally by people living along the Mediterranean littoral have been described earlier. "Cestodin". his compatriot. One of the earliest records of its use is the indication by a sixteenth century monk that Bitole. Its effectiveness was confirmed by several French medical authorities and it became popular not only in France but also in . They observed that it was prepared by steeping a handful of seeds of flowers in two quarts of beer all night then the bitter potion was drunk in the morning. In 1845. Dr Brayer. adopted the habit of taking it during his term of office from 1546-1554 124. however. The active constituents of pyrethrum powder obtained from these plants are pyrethrins. as tin preparations often contained traces of lead or arsenic that led to poisoning. Kousso (kosso) Tapeworm infections have been particularly common for many years among people living in Ethiopia as a result of the habit of eating raw beef.78 Chrysanthemum A History of Human Helminthology Flowers of Chrysanthemum have been used for centuries as anthelmintics. The most popular of these was kousso which was derived from the blood-red flowers and seeds of the tree Hagenia abyssinica (= Banksia abyssinica = Brayera anthelmintica). publicized its effectiveness in the 1820's125. these substances are also powerful insecticides. however. the fourth Golla chief. Little is known of practices in Africa south of the Sahara. The drug attracted the attention of Spanish and Portuguese Jesuit missionaries in the early seventeenth century.000 doses to Paris. there was also considerable interest in that country in developing taenicides. Consequently. This was somewhat dangerous. a combination of metallic tin. tin oxide and tin chloride was used until recent years. until the Frenchman. An important remedy in northeastern Africa. Tin Metallic tin has been used to treat tapeworm infections for centuries. Little interest in this preparation was shown in Europe. kosin and kosotoxin. "Ping-lang" (Areca catechu = betel nut). Then discard the sedimented particles and add to the fluid 1 liang Fen (lead carbonate) and 4 liang Mi (honey). juice of the leaves or the head of the wild date palm (Phoenix dactylifera. Traditional anthelmintics still in use in India at the beginning of the present century were derived from the leaves of Clerodendrum infortunatum. Its popularity waned in Europe in the latter part of the nineteenth century but it is still widely used in Ethiopia today. fruits of Embelia ribes. with increasing availability. The most popular plants were "Lei-wan" (Mylitta lapidescens). and take the entire solution after rising in the morning. 752 AD): "Suan-shih-liu-ken. after sifting. For tapeworm: T'ang dynasty (c. Mix the above. The active principles were identified as phloroglucinol derivatives. a."159 c. pig's blood. "Shih-liu-p'i" (Punica indica = pomegranate) and Mallotus philippinensis (= kamala). For Ascaris: Han period (c. there was little change in the products used over a period of 2. its price fell. "Shih-chun-tze" (Quisqualis indica). ash of human hair. Several examples of Chinese anthelmintic prescriptions are listed below. A major problem initially was its expense but. mercury and arsenic.650 AD): "Take one ball of human hair about the size of an egg burned into ashes. herbal remedies were popular in the Orient.Anthelmintics 79 Britain. Then filter and divide the total solution into three equal parts. a number of substances of mineral and animal origin were used. Among the former were included sulphur.220 AD): "Decoct 2 liang (1 liang = 36 gram) of Kan-ts'ao (= Glycyrrhiza glabra) in 3 sheng (1 sheng = 1 litre) of water until 2 sheng of the fluid is left. ASIA As in the West. Kousso was finally given a place in the British Pharmacopoeia in 1863. Decoct the first two drugs in 6 sheng of water. Likewise in China. Take successive doses at intervals equal to the time required for a five-li walk. will effect an immediate cure. 1 sheng of which taken warm. baked toad and snake skin."30 b. Admix the powder of the seed of Ipomoea when the drug is to be taken. with bitter wine. root of Punica granatum (pomegranate) one handful of its branches directing eastwards.000 years78. All the worms will be killed and passed out. tin. Stir thoroughly and decoct the mixture again to a solution like congee. and from the leaves of Costus speciosus as well as the root of the pomegranate (Punica granatum). In addition. For Enterobius: T'ang dynasty (c.176 . related to filicic acid of male fern26. 3 liang Wu-i (Ulmus macrocarpa) and one half liang powdered Ch'ien-niu-tzu seed (Ipomoea hederacea). Animal products with supposed vermifugal properties included chicken faeces. "Ho-shih" (Carpesium abrotanoides). lead. It became popular in Europe for the treatment of tapeworm in the nineteenth century and was entered into the British Pharmacopoeia in 1863. particularly Cucurbita pepo. a seaweed from the west of Argentina78. Such a technique is described by Sun Szu-Miao in the T'ang dynasty (c. the chewing of betel nut has been practised for at least 1400 years and has built up a reputation as a taeniafuge. These include a legume (Mucuna pruriens). The active component. decoctions being prepared in alcohol. for example. has been isolated and identified as an amino acid. put the powder into the liquid. the cebadilla (Spigelia anthelmintica) in tropical America as well as Fucus helmintocorton. the popularity of this remedy spread to Europe. Its popularity waned with the appearance of more efficient agents in the twentieth century. 3-amino-3-carboxy pyrrolidin26. The worms will come out.650 AD): Grind 14 pieces of Ping-lang (Areca catechu) into powder and sift. The seeds were generally minced into a paste and swallowed. arecoline26. From there. After filtration.159 The active principle is the alkaloid. cucurbitine. however. powdered nut. The most important American plant products. Like male fern and kousso. recommended consumption of pumpkin seeds for taeniasis in 1683171. oil of chenopodium and leche de higueron. According to Liu102. the active constituents are ploroglucodins such as rottlerine which paralyse the cestodes26. Areca catechu. Pumpkin seeds Pumpkin seeds. Kamala Kamala is a resin derived from the glands and hairs covering the fruits of Mallotus philippinensis (= Rotteria tinctoria) which is widespread in Asia and has been used as a folk remedy for centuries.80 Betel nut (Areca) A History of Human Helminthology Betel nuts are seeds of the palm. THE AMERICAS A number of plants have been held in some traditional regard as vermifuges.5 sheng of water until half a sheng of the liquid is left. . were pumpkin seeds. Then boil the shells of Ping-lang in 2. have been used in tropical America for centuries as a treatment for tapeworm infections. Tyson in England. Drink the solution from time to time and lie in bed and keep warm. which is widespread in southern and eastern Asia. It may also be administered in the form of a decoction obtained from the dried. a volatile terpene. seeds and flowering tops have all been used to produce decoctions. Malaya (Malaysia) and Fiji in the 1920's and then in Brazil in the 1930's. plants were taken to Europe. however. as an anthelmintic. Jerusalem oak and "epazote" or "paico"89. headache. ascaridol. ficin. was isolated and eventually synthesized 27. is a protease related to papain27. popularly known as American wormseed. became the common form of the drug throughout the nineteenth century and during the first half of the twentieth century. laurifolia. Archaeological and ethnological studies suggest that it has been used for many centuries. The extracted oil of chenopodium. In view of its easy availability and cheapness. . Wucherer remarked in 1866 that it was effective in the treatment of hookworm infection180 then in 1912 Berrio reported that it was useful for trichuriasis 12. Nevertheless. cultivated widely.Anthelmintics Oil of chenopodium 81 The most widely used indigenous plant anthelmintic from the Americas is oil of chenopodium derived from Chenopodium ambrosioides. effective anthelmintics led to its official abandonment. and this together with the development of other safe. Moreover. Bruning began to use it successfully in 190917 then this was confirmed by Schüffner152. The active principle. tachycardia and rarely death were recognized with increasing frequency. reported that it was used by both the indigenous inhabitants as well as European settlers in the American colonies for the treatment of Ascaris 83. The plant was illustrated in a sixteenth century codex concerned with the Aztecs49. a recent study of traditional village use of Chenopodium extracts has cast doubts on its efficacy89. a Swedish botanist and traveller. Toxic reactions including gastrointestinal upsets. The active principle. Mexican teak. oil of chenopodium was employed with considerable success by the Rockefeller Foundation in hookworm campaigns in the Dutch East Indies (Indonesia). Ficus glabrata and F. Although Baumler (1881) and Breton (1905) in the United States of America had tried oil of chenopodium without success in ancylostomiasis. Wild plants have been found growing in association with long-abandoned Pueblo ruins while the pre-Columbian Maya of Yucatan in Mexico called it "lucum xiu" meaning "worm-plant"139. Peter Kalm (1715-1779). This aromatic herb is found as an annual weed in locations varying from Argentina in the south to Canada in the north. In the early eighteenth century. The milky fluid (latex) has been called leche de higueron or lait d'higueron. and were soon in common use. usually prepared by boiling. deafness. it continues to be used by millions of urban and rural people in the third world for the treatment of intestinal worm infections. The leaves. In 1723. Leche de higueron The inhabitants of equatorial South America and Central America have long used the sap of the figs. He divided these agents into three groups "purgatives" which expelled helminths from the gut by increasing intestinal secretions and stimulating peristalsis. Those substances that really were important anthelmintics are all traditional remedies and have been described already. Those that were considered to be of greatest value were listed by Rudolphi at the beginning of the nineteenth century (Table 3. "mechanical irritants" which were supposed to cause the worms to relax their hold upon the gut mucosa so that they could be expelled more readily by purgatives. 379 were vegetable in origin. . (Glaubers' salts etc) Olea expressa Olea ricina (castor oil from Ricinus species) Oleum nucum Scammoneum (scammony from Convolvulus scammonia) Helleborum (hellebore from Helleborus species) True anthelmintics Stizolobium (from cowhage. Macuna pruriens) Aqua frigida (ice water) Oleum Chaberti (Chabert's oil) Oleum animali Dippelis Oleum terebinthicae (turpentine from Pistacia terebinthus) Petroleum Oleum cajeputi (from Melaleuca) Camphora (from Camphora officinarum = Laurus camphora) Artemisiae judaicae sive cinae semen (semen-contra-vermes) Tanaceti vulgaris semina Helminthocorton Goeffroeae surinamensis cortex (bark of Geoffroea surinamensis) Polypodii (Aspidii) filicis maris radix (root of male fern) Spigelias ____________________________________________________________________ NINETEENTH CENTURY When Clericus in Geneva reviewed human helminthology in his book in 1715. Of these.1). 27 were derived from animal products. ammonia etc.82 A History of Human Helminthology Table 3.1. he tabulated the substances believed to have an anthelmintic action that were known in Europe at that time36. Glaubers. and 13 were minerals. Major anthelmintics listed by Rudolphi140 ____________________________________________________________________ Mechanical irritants Stannum purum et granulatum (tin) Purgatives Salina. and "true vermifuges" which poisoned the parasite. Antimony therapy of schistosomiasis was taken up enthusiastically and. In addition. The relative advantages and efficacies of these compounds are discussed further in chapter 8. Pentavalent antimonials were found to be ineffective in schistosomiasis but a number of trivalent organic antimony compounds including sodium antimony tartrate. Betanaphthol Betanaphthol is a synthetic naphthalene derivative which was first used as a treatment for hookworm by Bentley in 190411. potssium antimony tartrate) was extremely effective in human infections with Schistosoma haematobium and S. mansoni 31. Antimonials In 1918. he suggested its use in the treatment of human hookworm infection71. Having swallowed some himself without ill-effect. The effectiveness of this drug in ancylostomiasis was soon confirmed7. Its side-effects.Anthelmintics 83 FIRST QUARTER OF THE TWENTIETH CENTURY One major advance in the chemotherapy of helminth infections was made during the first quarter of the twentieth century. despite some toxicity. lithium antimony thiomalate (anthiomaline). were developed. led to its falling into disfavour. Bismuth Bismuth carbonate was used by Loeper in 1921 for the treatment of enterobiasis but did not enjoy wide favour104. particularly in causing haemolysis and renal damage. Carbon tetrachloride In 1921. a number of other compounds with some anthelmintic efficacy were described. Doubts soon arose about its toxicity when a number of people died of liver .99 and it was also reported to be useful in tapeworm infections143 . Christopherson reported that the antimony compound. sodium antimony gluconate (triostam) and sodium antimony dimercaptosuccinate (stibocaptate. tartar emetic (antimony tartaratum. remained the cornerstone of treatment for these infections for the next forty to fifty years. Hall reported that carbon tetrachloride was a useful anthelmintic in animals with intestinal nematode infections70. stibophen (fouadin). astiban). This was the discovery that antimony compounds when administered intravenously were effective in the treatment of schistosomiasis. His serendipitous discovery of the use of this drug for schistosomiasis while treating a patient with kala azar is detailed in chapter 8. rarely cause death. Hawking noted that phenyl arsenoxide derivatives were microfilaricidal in vitro but little attention was paid to this observation because of the distractions of war74. These drugs influenced many helminth infections and ranged from the introduction of tetrachlorethylene in the treatment of hookworm infection to the use of lucanthone for the therapy of schistosomiasis and diethylcarbamazine for filariasis. A soluble derivative. Arsenamide (thiacetarsamide) was used in humans infected with Wuchereria bancrofti 166 amd Onchocerca volvulus 122. For similar reasons.84 A History of Human Helminthology failure158. a tree indigenous to tropical America. Otto and Maren noticed an action of arsenicals against both adult worms and microfilariae of Litomosoides 121 and Dirofilaria immitis 122. kidney and brain. bancrofti by Culbertson 41 and found to be moderately effective but dangerous. SECOND QUARTER OF THE TWENTIETH CENTURY The pace of discovery quickened considerably during the second quarter of the twentieth century. In 1905. Unfortunately. Melarsenoxide was used against W. They therefore fell into disrepute for the treatment of filarial diseases since these conditions. although they may produce significant morbidity. The most effective preparations were arsenamide and several melarsen derivatives. particularly to the liver. Blair had claimed that sodium arsenite produced clinical improvement in dogs with heartworm infection but produced no supporting parasitological details. however. . Neoarsphenamine was soon tried in bancroftian filariasis with disappointing results. A few years later. Arsenicals Arsenical compounds were introduced by Erlich for the treatment of trypanosomiasis and syphilis at the dawn of the twentieth century. Cashew nut oil (oil of anacardium) Cashew nut oil is obtained from Anacardium occidentale. In 1940. The oil was shown to be effective in canine ancylostomiasis then was used with some effect in human hookworm infection53. these drugs may be highly toxic. arsenicals have been little used in intestinal nematode infections although acetarsol was employed in enterobiasis by Perrin in 1927132 and diphetarsone was tried in trichuriasis by Junod83. melarsenoxide potassium dimercaptosuccinate (Mel W) was also tried in bancroftian filariasis106 and onchocerciasis 62 a few years later. and it fell rapidly into disuse. Chung and colleagues claimed some value for the drug in the treatment of paragonimiasis 32 while others believed it had a place in the management of opisthorchiasis 142. Mazzotti then noted that microfilarial numbers in the skin built up again to pre-treatment levels over the next few months112. a number of investigators reported that diethylcarbamazine produced some clinical improvement in patients with loiasis154. Later in the same year. In 1949.156. Diethylcarbamazine In 1947. Danaraj in 1958 observed that the ill-defined filarial infection. diethylcarbamazine. Kudiche showed in 1925 that the related compounds. Likewise. tropical pulmonary eosinophilia. it has also been used for the treatment of gastrointestinal nematode infections. responded dramatically and permanently to diethylcarbamazine treatment45.and hexylmethyl derivatives of rosaniline. crystal violet and fuchsin. While diethylcarbamazine was thought to be moderately valuable in ancylostomiasis 44. however. it was noted to be ineffective in enterobiasis 105. killed Strongyloides . Santiago-Stevenson described the use of diethylcarbamazine in humans with bancroftian filariasis and noted that it produced a dramatic fall in the numbers of circulating microfilariae144. Mazzotti and Hewitt found some reduction in the numbers of microfilariae in the skin after diethylcarbamazine treatment but observed living adult worms in extirpated nodules113. In 1948. Although diethylcarbamazine has been used primarily in filarial infections. Gentian violet and related dye-stuffs Gentian violet is a dye-stuff composed of a mixture of variable proportions of the tetra-. Subsequent observations. revealed that these effects were not sustained. Hewitt and colleagues in 1948 observed that it was effective in canine ascariasis77 then in the following year Oliver-Gonzalez and others showed that it was reasonably effective in humans infected with Ascaris lumbricoides 120. In contrast to all of these conditions. Basnuevo used it with some success in patients with fascioliasis 9. the effects of diethylcarbamazine in onchocerciasis were soon examined. para. was active against Litomosoides carinii in cotton rats and against Dirofilaria immitis in dogs76. This anthelmintic was the result of a research programme initiated because of the large number of American veterans who had acquired filariasis during World War II. Hewitt and his colleagues showed that the piperazine derivative. The majority of these patients did not have microfilaraemia. and it took some little time for it to become clear that the reduction in microfilaraemia was transient. however.Anthelmintics Chloroquine 85 Chloroquine was introduced in the 1940's as an antimalarial agent. Within a year or two. Subsequently. Ruikka showed in 1951 that it was also effective in diphyllobothriasis 141. Palmer123 gave gentian violet by slow intravenous injection in this condition then Schreiber 151 extolled its value when given by duodenal intubation. Mepacrine (quinacrine. however. Nevertheless. Wright and Bray in 1938 used gentian violet for the treatment of enterobiasis179 but much more effective drugs are now available. believed that adult worms were killed in situ 56 then in 1932 claimed that 95% of patients were cured by oral gentian violet57. . Shortly afterwards. Mepacrine became a very popular treatment for tapeworm infections until the introduction of niclosamide. Hexylresorcinol Hexylresorcinol is a phenol which was shown by Lamson and his colleagues in 1931 to be effective in the treatment of ascariasis 95. de Langen reported that oral administration of gentian violet in conjunction with intravenous injection of tartar emetic was effective in strongyloidiasis 97 but in the following year he acknowledged that his patients had relapsed98. Its efficacy in experimental schistosomiasis was first shown by Kikuth and colleagues during World War II2 then this was reported several years later88. the preponderance of opinion was that the drug was of little value in the treatment of strongyloidiasis. nilodin) was the first schistosomicidal drug which was metal-free and orally active. atabrine) Mepacrine was originally synthesized as an antimalarial compound in 1932. This drug was then used clinically as hycanthone methanesulphonate (etrenol)35. It then became the treatment of choice for hymenolepiasis until recent times. Experimental and clinical studies indicated that it was most active against Schistosoma haematobium. less active against S. In 1939. Lucanthone and hycanthone Lucanthone (miracil D. atebrin. solium infections118. on the basis of experiments in monkeys. It was shown eventually by Rosi and co-workers that the active form was an hydroxymethyl derivative now known as hycanthone138. mansoni and had little effect on S. Neghme reported that it was useful in the treatment of Taenia saginata and T. Concern was expressed about possible mutagenic effects. Likewise.86 A History of Human Helminthology stercoralis infective larvae in vitro 91. Maplestone and Mukerji reported that it was active againt Taenia saginata 110. hexylresorcinol has been used in fluke infections such as fasciolopsiasis108. and it was eventually replaced by more effective and less toxic agents. In 1928. Faust. japonicum. In 1929. Manson-Bahr then showed in 1940 that it was effective in humans infected with Enterobius vermicularis 109. This drug was so superior to all previously available agents for the treatment of ascariasis and enterobiasis that Bueding and Swartzwelder in 195718 considered its discovery to be one of the most important turning points in development of the chemotherapy of helminthiasis. however. Its effectiveness was confirmed by Schapiro and Stoll148. Piperazine was prepared in a number of forms including the hydrate. This observation was taken up by Mehrez who in 1947 confirmed its effectiveness 115. . Suramin (antrypol) Suramin was introduced in 1921 for the treatment of trypanosomiasis. This action was then confirmed by Ashburn and colleagues 4. Although it still had significant toxicity. and it has not found a place in the treatment of filariasis and its role in the management of onchocerciasis remains doubtful. that this drug may cause serious toxic effects. during experimental infections on trypanosomiasis in volunteers. citrate. It was observed. Piperazine (diethylenediamine) In 1942.Anthelmintics Phenothiazine 87 The anthelmintic properties of phenothiazine were first recognized by Harwood and colleagues who reported in 1938 that it eliminated ascarids from the intestines of swine73. Giroud noted that a patient infected with Enterobius was cured when treated with piperazine. adipate and phosphate compounds. particularly to the kidney. Tetrachlorethylene Tetrachlorethylene was introduced by Hall and Shillinger in 1925 for the treatment of hookworm infection72 four years after the advent of carbon tetrachloride. Two years later. Subsequently. Lamson and colleagues showed that this drug was significantly less toxic than carbon tetrachloride 96. Piperazines were shown rapidly to be ineffective in the other major intestinal nematode infections but they are still widely used in many countries as inexpensive. less toxic agents soon became available for the treatment of intestinal nematode infections. Fayard described its efficacy in ascariasis58. Thooris showed that it killed Wuchereria bancrofti adult worms as well170. it remained a very popular anti-hookworm therapy for several decades. In 1945. fortuitously discovered that it also acted upon Onchocerca volvulus adult worms (cited in177). popular anthelmintics. van Hoof and his colleagues. However. 160 and Strongyloides stercoralis 160. A number of new drugs were developed for the treatment of schistosomiasis. Likewise. ancylostomiasis and enterobiasis.137. Dithiazanine Dithiazanine iodide is a dicarbocyanine dye which was demonstrated as having anthelmintic properties in experimental animals by MacCowen and colleagues in 1957107. bephenium was the most interesting37. Ancylostoma and Trichuris infections in cats and dogs.157 and the drug was . Bephenium In 1958. cati in felines21 then was shown to be superior to tetrachlorethylene in the treatment of human ancylostomiasis 66. In the same year. The distinctive feature of dithiazanine in contrast to earlier anthelmintics was that while it had limited activity in ascariasis. It was then shown to expel Taenia saginata 183 and Diphyllobothrium latum 116 from humans. They showed that it was effective against Ascaris. the drug was noted to be effective also against Ascaris lumbricoides 66 and to be variably effective in trichostrongyliasis 68 and heterophyiasis117 but ineffective in enterobiasis and strongyloidiasis. it was active against Trichuris trichiura 63. Copp and his colleagues reported the discovery of quaternary ammonium compounds effective against intestinal nematodes.153. of these. These actions in human intestinal infections were confirmed in the same year. Unfortunately. and the benzimidazole series of anthelmintics appeared.88 A History of Human Helminthology THIRD QUARTER OF THE TWENTIETH CENTURY Wide ranging advances in anthelmintic therapy occurred in the third quarter of the twentieth century. at least eight deaths due to dithiazanine administration occurred1. encouraging reports appeared of its value in taeniasis175 and clonorchiasis 181. Its use in human Taenia saginata infections was first suggested in 1956114. Dichlorophene This halogenated hydroxyphenylmethane was shown in 1946 to be active against tapeworms in dogs40. niclosamide became available for the therapy of tapeworm infections. Bithiniol Bithiniol was described originally as a bactericidal and antifungal agent but in 1957 Sawada reported that it was active against the chicken tapeworm Raillietina kashiwarensis 147. the drug was reported to be an effective agent against Ancylostoma caninum and Toxocara canis in dogs and T. Moreover.184. niridazole was more active against S. In 1963. In 1960. Niclosamide remains one of the drugs of choice for the treatment of tapeworm infections. Metrifonate Metrifonate is an organophosphate compound. Subsequent experience indicated that this drug was particularly useful for S. mansoni . World-wide clinical trials followed and it was shown that it was active against practically all the tapeworms of man42. Two years later. Their use as anthelmintics in veterinary medicine was first described by Levine and colleagues in 1958100. Lambert reported that niridazole was active against Schistosoma mansoni infections in mice92. Screening studies showed that it was active against Hymenolepis diminuta in rats65. Lambert and Da Cruz Ferreira showed that it was effective in humans with urinary schistosomiasis in Portuguese Guinea (Guinea Bissau)93. Da Cruz Ferreira and co-workers reported on its use in ancylostomiasis but it was variably effective and caused some intolerance 43. Cerf and others showed that it was moderately effective against both Ascaris lumbricoides and Schistosoma mansoni 29. Niridazole In 1964. clonorchiasis 182. haematobium 163. niclosamide (molluscicide Bayer 73). haematobium infections and it was not used for other forms of schistosomiasis 59.90. Talaat and colleagues confirmed this observation and also showed that metrifonate was active against S. Some success attended its use in human fascioliasis 133. paragonimiasis 33 and opisthorchiasis 134.Anthelmintics withdrawn from the market. haematobium than S. Hexachlorophene Hexachlorophene was tried in clonorchiasis with mixed success by Chung and colleagues 34 and by Liu103. Further observations revealed that in humans. In the following year. These substances have been used as insecticides since the 1950's. Hetol (chloxyl) 89 This chlorinated benzene derivative (1.4-bis trichloromethylbenzene) was shown to be effective in the treatment of fascioliasis in various animal species by Lämmler in 196094. Niclosamide In 1960. Gönnert and Schraufstätter described a new molluscicide. Oxamniquine In 1973. japonicum 60.90 82 A History of Human Helminthology and least active against S. Subsequent studies indicated that oxamniquine was more active against South American than African strains of S. haematobium and S. In the following year. Ulivelli reported in 1963 that it was effective in humans with taeniasis172. Niridazole held pride of place in the treatment of urinary schistosomiasis for a short period but has now been largely displaced by less toxic drugs. Three years later. Katz and his colleagues tested the efficacy of the drug when given by oral and intramuscular routes to humans with schistosomiasis in Brazil and observed that the latter route was preferable85. Stilbazium The anthelmintic actions of stilbazium iodide in infected animals were first escribed by Burrows and colleagues in 196122. mansoni 162. Swartzwelder and co-workers reported that it was effective in humans infected with Ascaris lumbricoides. Bumbalo and co-workers showed that it was useful in human enterobiasis 19 then in 1970 Desowitz and others found that it was effective in ascariasis and hookworm infection but not in trichuriasis 48. Oxantel Oxantel is an analogue of pyrantel that was shown to be effective in trichuriasis by Lim in 1974101 but has little effect on ascariasis and hookworm infection. Enterobius vermicularis and Trichuris trichiura but was of little value in ancylostomiasis 161. Pyrantel In 1966. . This drug has not found a permanent place in the therapeutic armamentarium. In the same year. Austin and colleagues reported that pyrantel was an effective broadspectrum anthelmintic in domestic animals5. Paromomycin Paromomycin is an antibiotic with antibacterial and amoebicidal properties. japonicum 145. It has therefore been used sometimes in combination with pyrantel. especially praziquantel. Foster and colleagues reported that oxamniquine was active against Schistosoma mansoni in rodents and monkeys although it was inactive against S. Gordon indicated that it was highly effective against nematode infections of the gastrointestinal tract of sheep67. Mebendazole. trichuriasis and ancylostomiasis by Pene and co-workers in 1981130 but to be of variable effectiveness in strongyloidiasis 38. however. it has been suggested that albendazole may be better than mebendazole in the treatment of infections with Echinococcus granulosus and E.64 . was more active against Ascaris lumbricoides than the racemate and was useful in hookworm infection and possibly in strongyloidiasis but was not effective in trichuriasis or enterobiasis 166.129 . revealed that its activity was relatively poor in hookworm infection. More recently. It was soon noted to be also active in ascariasis 64. Thienpont and his colleagues described tetramisole as a potent broadspectrum veterinary anthelmintic 167. ancylostomiasis and strongyloidiasis but inactive in trichuriasis. trichostrongyliasis3 and capillariasis 155 but to be of doubtful efficacy in strongyloidiasis. Albendazole and other Benzimidazoles Thiabendazole was introduced in 1961 when Brown and his colleagues showed that this agent had broadspectrum activity against intestinal nematodes in pigs and horses15. ascariasis. In 1969. Do Nascimento and colleagues showed that it was effective in humans with ascariasis 51. ancylostomiasis8. enterobiasis54 . cestode and nematode infections in animals was described by Théodoridès and colleagues in 1976164. Later in the same year. Subsequently. multilocularis 128.119. trichuriasis64. The drug was then tried in human infections and was found to be variably effective in 81. levamisole. Flubendazole. was reported to have similar activity to that compound by Schenone and colleagues 149. mebendazole was shown to be of some value in intestinal taeniasis87. Cambendazole was used in strongyloidiasis with good effect by Martirani and Rodrigues in 1976111 but the drug has since been withdrawn from the market.173 61. experimental studies in animals suggested that it may be of value in echinococcosis 75 then it was used with partial success in humans with hydatid infections by Bekhti and colleagues in 197710.129. It was shown to be effective in a number of human gastrointestinal nematode infections including enterobiasis. trichuriasis and strongyloidiasis. Thiabendazole. In addition. The activity of albendazole against certain trematode. . Later that year. a fluorine analogue of mebendazole. Subsequent observations. Thienpont and his collaborators showed that the levo-isomer of tetramisole.173 ascariasis81. Mebendazole was introduced in 1971 by Brugmans and colleagues who showed that it was effective in enterobiasis16.Anthelmintics Tetramisole and Levamisole 91 In 1966. 92 A History of Human Helminthology Viprynium (Pyrvinium) Viprynium pamoate is a cyanine dye. FINAL QUARTER OF THE TWENTIETH CENTURY The last quarter of the twentieth century is only halfway through but already two valuable new drugs. was active against Ancylostoma caninum 13 and Dirofilaria immitis 25 in dogs. 150 136 fascioliasis and paragonimiasis was reported. Subsequently. In 1984. cures for worms have been sought . latum infections23. a variety of antibiotics have been developed for the treatment of the vast majority of bacterial infections. Praziquantel Praziquantel was identified from a group of heterocyclic pyrazino-isoquinolines and found to have unusually broad anthelmintic activity. fasciolopsiasis . CONCLUSION It is only fifty years since the sulphonamides first appeared then penicillin ushered in the dawn of antibiotic therapy of bacterial infections.146. It was then shown in the same year to be of some value in human hookworm infection by Perez-Santiago and colleagues131 but its main role came to be in the treatment of enterobiasis. it was observed that ivermectin had extraordinary potency against a wide range of nematodes and arthropods. In that short time. revealed that it was active against Nematospiroides dubius in mice. In contrast. ivermectin. both Hales and Welch69 and Weston and others178 showed that it had anthelmintic activities in animals. Espejo showed that it was valuable in the treatment of infections with Hymenolepis. In 1953. Streptomyces avermitilis. Subsequently. In 1977. In 1978. its value in clonorchiasis135 . Coulaud and colleagues reported that it was useful in the treatment of humans with onchocerciasis 39. In 1979. ivermectin and praziquantel. 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The use of dithiazanine in the treatment of helminthiasis in Mexican farm labourers. Japanese Journal of Parasitology 11: 39-44.Anthelmintics 101 parasitos humanas. BRADY FJ. The treatment of Taenia saginata with bithiniol. 39-41. Norman. 102 A History of Human Helminthology . penetrates the liver capsule then migrates through the parenchyma to the biliary tree where it matures over two to three months Definitive hosts: sheep. urticaria in heavy infections Diagnosis: demonstration of eggs in the faeces of patients with patent infections Treatment: bithiniol. goats. in 1379. produces sheep liver rot Major synonyms: Distoma hepaticum. live in the biliary tract and produce eggs which are passed in the faeces. who was known as "Le bon berger".Chapter 4 Fasciola hepatica and FASCIOLIASIS SYNOPSIS Common name: liver fluke. pigs. cattle. leaf-like hermaphroditic worms. there is littl e 103 . humans etc. The flukes wer e probably found independently by numerous people in diverse places over many years. Distomum hepaticum Distribution: world-wide Life cycle: The flat. The cercariae emerge from the snail. meaning "The good shepherd". and appears to have been somewhat confused as to whether the worms were the cause of. then each miracidium escapes and invades a snail intermediate host of the genus Lymnaea. or the consequence of sheep rot. swim about in water. jaundice. Major clinical features: fever. then encyst on aquatic vegetation. 30 mm long by 13 mm wide. The first recorded reference to these worms was made by a Frenchman. Jean de Brie. had been commissioned by Charles V of France to write a treatise on the proper management of sheep and the production of wool . de Brie. migrates through the intestinal wall into the peritoneal cavity. malaise. abdominal pain. The miracidium becomes a sporocyst (an elongated sac without suckers or alimentary canal) which in the course of four weeks produces first-generation then second-generation rediae (characterized by the presence of a single sucker and a simple sac-like alimentary canal) and cercariae. praziquantel DISCOVERY OF THE ADULT WORM IN ANIMALS The name of the person who first found liver flukes and knowledge of when the observation was made have been lost in the sands of time. After ingestion by a mammalian host. The ova develop in water over two weeks or so. the enclosed metacercaria excysts in the duodenum. was uncertain of its precise nature. Although he did not describe the morphology of the parasite. then was included in the Dutch and English editions of the Select works of A. were frequently as ignorant as th e butchers. type of fish) 18. he concluded by this doubtful process of reasoning that this possibility was unlikely. when he recovered them from the liver of a castrated ram in 1668 68. of the worms which dwell in the bile. become such. Conrad Gesner mentioned "duva" or liver flukes in his monumental book. often considering the flukes to be leeches or cucurbitini (tapewor m proglottids). The worms were. he wondered: whether the aqueous swelling. the Italian physician. Twenty four years later (1547).e. he wrote to the celebrated microscopist. he took fluid from the vesicles and boiled it . referred to "flokes" (flukes) in the livers of afflicted animals 32. The afore mentioned authorities. He believed that the consumption by sheep of a herbivorous leaf known locally as "la dauve" (probably Ranunculus species) corrupted the liver to produce "a type of worm which putrefaction does eat and destroy the entire liver of th e animal"15. He provided illustrations of the parasite. Francisco Redi. Hieronymous Gabucinus. Since it did not coagulate as did fluid in eggs found in the ovaries of quad rupeds. Antony van Leeuwenhoek. shaped like the seeds of a melon or gourd could possibly be the embryos. This name is thought to have been derived from the old Anglo-Saxon word "floc". He observed 18 worms swimming in the bile and remarked that their shape resembled somewhat the fish calle d sole. Because of the concurrence of the two forms. referred to worms resembling pumpkin seeds that he had often found in the livers o f sheep and goats 34. this wa s published as a memoir in that year 8. Faber (1670). He encountered them again in 1684 in a hare whic h also harboured large numbers of "hydatids" (pr esumably Cysticercus pisiformis ) in the mesentery and in the perit oneal cavity. He was followed by Fromma n (1663)33. Wepfer. A study of these worms was then taken up in earnest by the Dutchman . The parasites were discussed again in 1523 by the English lawyer. They were discussed again by the Dutchman. In 1551. in the section on sheep rot in the book on animal husbandry traditionally ascribed to him. upon growing and perfecting themselves. In a letter dated 21 March 1698. in his 1575 accoun t of an epidemic of fascioliasis which had occurred in Holland in 1562 35. of course.69 In order to test this possibility. those i n Florence referring to them as "Biscioule". Borel and others. Cornelius Gemma. and those in Provence naming them "Dalbères". who. those in Holland calling the m "Bottiens".104 A History of Human Helminthology doubt that he recognized the worm we now know as Fasciola hepatica. detailing his findings. and whether they. Leeuwenhoek (1679). Anthony Fitzherbert (1470-1538). meaning a flounder (i. I would not affirm this with certainty. Historia Animalium 36. so to speak. The first person to investigate and illustrate these parasites further was th e Italian physician. However. van Leeuwenhoek . noted its size and shape (which he compared with sole an d . well-known to the butchers of the time. Godefridus Bidloo. however. worms similar to those commonly encountered in the livers of sheep and cattle 8. he noted: Notwithstanding my most diligent examination of these creatures. Passing references to human infection wer e made in the seventeenth century. hundreds of which. Concerning the ova. and its seem to me most probable that they are of that species called Hermaphrodites. Bidloo recalled having seen. Malpighi and Borel seem to have equated the fluke wit h cucurbitini (Taenia). I could never discover any difference of the sexes. According to Clericus. while Wepfer claimed to have often found the bile ducts of humans filled with "hirudinibus" (leeches). Although Bucholz's case wa s accepted by Davaine 24. Sommer and Macé. taken together. Pierre Borel noted that he had seen flukes. liver. however. a planarian. Küchenmeister46 noted that Bremser had later examined some of the worms which had been preserved and thought that they were really . Fromann and Wepfer regarded it as a kind of leech. in all sorts of animal s including humans and pigs. in human livers. especially in cattle and wrote: "In hepat e frequentes occurent vermus cucurbitini in homine et brutis. 8 Even though Fasciola had been known for many years. discovered eggs. Similarly. Rudolf Leuckart . Thus .. Emile Blanchard. Linnaeus appears at various times to have considered it as a leech. giving the wor m non-existent eyes. IN HUMANS Although this fluke had been found many times in animals. Again.Fascioliasis 105 flounder). the transparent skin and discussed its motion.8 and with respect to the sexuality of the flukes. which he called insects. Nevertheless. and I take them to be the spawn or eggs. He was followed a century later by Bucholz in Weimar who found a large number of flukes in the gallbladder of a convict who had died from a "putrid fever" 17. More than 100 years were to pass before the details of the fluke's anatomy were worked out correctly by a number o f investigators including Mehlis (1831) 56. Gabucinus. porcis etc. and a cestod e. "mihi asseruit in omnibus animalibu s insecta haec reperiri et se in hominibus. while Bonamicus. heart and circulatory system. Redi. In fact. Marcus Malpighi claimed that cucurbitine worms occurred frequently in th e livers of humans and animals. he di d discern correctly a bowel. and recognized that the creature s were hermaphroditic. praesertim i n bove"53. however. He was rather confused about parts of the internal anatomy. colour. was Pallas who in 1760 recounted observing worms in the hepatic ducts of a female patient during an autopsy in Berlin 66. are not equal to the size of a grain of sand. eos vidisse" 11. They are of a pale red colour. infection wa s rarely recognized in humans. writing. he recounted that he had found: an innumerable quantity of oval particles. The first person to clearly describe finding these flukes in a human. there was an imperfect perception of its structure and confusion as to its zoological position. or everyone equally prolifick. he examined green sods from the meadows . with the result that the disease was known for man y years as distomiasis. Retzius needlessly changed the name of the genus to Distoma.71. but eventually created the genus Fasciola in his group Intestina of his Class Vermes and named the parasit e Fasciola hepatica in 175851. seed or spawn. then Abildgaard designated the fluk e Distoma hepatica 1. stags.106 A History of Human Helminthology Distoma lanceolata (= Dicrocoelium dendriticum ). then nourish themselves on the bile and develop. as well as other small living creatures. ranging from generation by putrified o r decaying substances to the eff ects of excessive wetness or heat. The generic name is derived from the Latin word "fasciola" meaning "fillet" or "small b andage". become fixed there. Being conversant with the general view that infection was acquired by animals feeding on contaminated pastures. This nomenclature was followed by Zeder (1800) . he reasoned that the eggs might be carried into the biliary passages . NOMENCLATURE Linnaeus at first regarded the fluke as a slug. Chabert claimed to expel great numbers of flukes from a twelve year old girl with the aid of his empyreumatic oil 19. asserted tha t these suggestions were but "ideal tales" and "senseless imaginations". He laid: it down as a certain truth. Rudolphi (1808-1810) and Dujardin (1845). no doubt girded by his discovery of eggs in the flukes.worms with multiple openings) 70. that these.and Polyostoma . according to the nature implanted in them at their first creation. by the means of eggs. Goeze believed that the organism was a planarian and at one time called it Planaria latiuscula. the Linnean designation regained pride of place through Opinion 84 of the International Commission on Zoological Nomenclature 41. that the adult worms forced their way from the gut into the gall bladder and biliary system . In 1786. Some years later. while Diesing (1849-1851) called it Distomum hepaticum.worms with a single opening . meaning two openings (as opposed to the Monostoma . are produced from their like. With the establishment of the law of priority i n nomenclature in the early part o f this century. Rather. ELUCIDATION OF THE MODE OF TRANSMISSION: DISCOVERY OF THE LARVAL STAGES AND SNAIL INTERMEDIATE HOSTS Early students of Fasciola suggested all manner of means by which the worms were produced and propagated.8 Bidloo thought it most probable that the worms bred in moist earth then were swallowed together with their eggs in water by herbivorous animals such a s sheep. Bidloo's correspondence with Antony van Leeuwenhoek encouraged th e Dutch microscopist to investigate the manner of transmission of this infection. calves and wild boars. however. Bidloo in 1698. He did not believe. however. however. Fasciola hepatica was the first fluke of human importance to be discovered. where the bladder of the gall doth empty itself. He noticed that many of these cercariae transformed into a "pupa" or "encysted" on foreign bodies. swim against it. and also the first one in which the life cycle was worked out. He called these sacs "roya l yellow worms" (or "king's yellow worms"): When the Lymnaea (snails) were taken from the dish. he concluded in 1817 that a cercaria was a combination of a Distomum with a Vibrio which he believed provided the characteristic tail of the cercaria 61. 94 An understanding of the mode of development of Fasciola hepatica took so long to achieve for several reasons. The way in which this was achieved. They did not appear to have any sexual organs so many authorities invoked the doctrine of spontaneous generation to explain their existence.. in the early part of th e nineteenth century. consi dered them to be Infusoria. and came some way towards realizing that they wer e trematodes. however. but the concepts involved were unknown in the eighteenth century and were appreciated only gradually during the nineteenth century . h e noticed that cercariae crept out of s acs in the viscera of the snails and concluded that they were probably generated within them. active movement . He regarded them as independent adult creatures. (now East) Germany. In 1773... He noticed the resemblance of the anterior part of the body of a cercaria to a fluke (Distomum). In 1818. but was of the opinion that this process merely signified the termination of life 60. a professor in Halle. 47 and thus enter and lodge in the biliary system. living. Youatt in his book on sheep claimed that: Rot is caused simply by the extrication of certain gases or miasmata during the decomposition of vegetable matter. under the influence of moisture and air. living free in water 58. The origin of these cercariae was a puzzle. A study of these organisms was then taken up by CL Nitzsch. many author ities strayed far from the mark. OF Müller discovered microscopic organisms. Cercaria. As late as 1837. While dissecting some snails from a fresh-water pond. Nitzsch also recognized that cercariae were not Infusoria. but being convinced that infection must be acquired by ingestion. but in movement very indolent. a large number of royal yellow. the Prussian. Both Bidloo and Leeuwenhoek were close to the truth. During this period. Sadly. under the microscope. Not only was the life cycle of this parasite extremely complex. cylindrical worms (Distomata?) were found in many of them. a professor at Wilno (now Vilnius) in present-day Lithuania made a momentous discovery. he speculated that when the worms reached: the beginning of the guts. can only be und erstood when viewed in a wider context encompassing discoveries with various non-human parasites. and gave them the generic name. however. he communicated his failure to find any such animals to the Royal Society of Londo n.In the yellow worm one saw. which we now know to be the larval stages of trematodes. but nearly 200 years were to pass before the life cycle of Fasciola hepatica was finally elucidated.Fascioliasis 107 on which some infected sheep had fed seeking microscopical creatures re sembling the adult flukes. As a result of such observations. these animals being pleased with the taste of the gall. Ludwig Bojanus. Meanwhile. Again it caused some surprise that the embryo.. Although he was not able to actually witness the process. in whose journal Bojanus published hi s discovery. but rather that the swimming embryos might seek out their hosts themselves 62. 10 These yellow royal worms were given the generic name Redia by de Filippi in 1837 in honour of Francesco Redi 30. These he recognized as being identical with certain cercaria-sacs that he had seen in snails. The story was taken a stage further in 1831 when Karl Mehlis. All those that slipped out by themselves had the appearance of the previously described cercariae. at various places. he theorize d that the adult trematode worms produce e ggs from which the larvae hatch. Several years later (1837) Friedrich Creplin (1788-1863). (now East) Germany. he had occasion t o examine large numbers of the fluke Monostomum mutabile which lived in the orbital cavities of geese. that the old hypothesis that infection was acquired by ingestion of eggs was finally laid to rest 78. but also saw an infusorian-like ciliate d embryo slip out of many eggs of the flukes. While District Medical Officer in Heilsberg (no w known as Lidzbark) in East Prussia (present-day Poland). Oken. The discovery of these motile worms led von Nordmann to point out that the ability of the flukes' progeny to swim about in water suggested that hosts were unlikely to become infected by passively ingesting eggs.108 A History of Human Helminthology which came from the enclosed winding animals. a medical practitioner and zoologist in Greifswald. Carl von Siebold had linked the embr yos released from fluke eggs with rediae and cercariae. not only discovered th e operculum (lid) of each fluke ovum. a medica l practitioner in Clausthal in (now West) Germany... remarked that "observations of this kind make one dizzy" 64 and added that "one might lay a wager that these cercariae are the embryos o f distomes"63. meanin g "youthful person" by Braun 12 should be so different in appearance from th e parent worm. This hypothesis was eventually prove n correct when G Wagener observed the metamorphosis of the miracidium o f . it was not until Simonds showed in 1852 that not a single fluke was found nor were any traces of liver rot present in sheep fed fluke eggs. It caused much astonishment that cercariae were no t derived from parents resembling themselves. After a while. Nevertheless. He noted the hatching of ciliated larvae from the eggs and watched them swimming around in the water. This observation of Bojanus was confirmed by CE von Baer i n 1827. de Filippi later accepted the view that the redia was a larval stage and recommended that the name be no longer used to designate a genus31. but came from these peculiar . worm-shaped sacs. each one releasing from its interior a motile. swim around to find an appropriate snail. in breaking through. showed that the eggs of Fasciola hepatica likewise hatched a ciliated larva 23. finally. they died and disintegrated. Monostomum flavum and Distomum hians 56. later to be called a miracidium. animated. then die releasing cercaria-sacs (rediae) 75. cylindrical body with two short lateral processes and furnished with a pharynx and simple gut.Some of the enclosed animals succeeded. penetrate the tissues of the new host. A von Chamisso. but they provided a n indispensable principle upon which the details of the life cycles. a form of marine animal. His view s required both correction and completion. not only o f trematodes but also of cestodes. He synthesized many reports in the literature with his own observations. who had shown that in the Salpae. and that whole divisions of families must be abolished because they included only undeveloped forms. Redia and Distoma were unrelated organisms. The consequences of this statement wer e that cercariae were the progeny of trematodes. eac h deserving and occupying separate generic sta tus in the schemes of classification. other authoritie s . underlying law of nature throug h which all the phenomena that had seemed devoid of plan could be brought t o order. just as the polyp originating from the eggs of a medusa represented a n alternate generation. Steenstrup knew that C. and found a phenomenon common to all of them that he summarized in the followin g terms: An animal bears young which are. To others. Despite the observations and hypotheses mentioned above. dissimilar to their parent. Steenstrup gave an account of the evolution of coelenterates (Medusae an d claviform polyps). that these worms passed part of their existence in a state of freedom. free individuals and individuals bound together i n chains alternated with one another in each successive generation. most authorities held that Cercaria. Johannes Steenstrup. but bring forth a new generation. 81 Thus. of pelagic tunicates (Salpae). Steenstru p observed that in some of the Trematoda the latter generations remained within the earlier forms until they attained their full development whereas other s forsook them earlier to become free-swimming then underwent a complet e metamorphosis. In his work. return to the original form of the parent animal. He conjectured fur ther that cercariae might penetrate into other animals. and of trematodes. all these seemingly irregular phenomena constituted a complete chaos which appeared to break down all the known laws of anima l existence and propogation. or in their descendants. Although some investigators such as von Siebold (1844) 76 and van Beneden (1852) 7 seized upon this idea of alternation of generations. particularly in his supposition tha t final maturation occurred in the body of the snail. echinata encysted in snails. so did the royal yellow worm (cercaria or redia) derive d from the ciliated embryo of a fluke. could be fleshed. then in 1842 he published a book in which he promulgated his doctrine of the "Alternation of Generations" 81.Fascioliasis 109 Distoma cygnoides of the frog into a redia in 1857 88. This term had already been used in 1819 by the German poet and navigator. entered the scene. and remain. He succeeded in evolving a certain plan out o f this confusion by the discovery of a hidden. The fate of the cercariae thus produced remained uncertain although von Siebold reported in 1837 that some cercariae such as C. lose their tails and become adult flukes. echinata encysted in snails so he extracted parasites from the cysts after various periods and showed that they contained typical fluke-like forms. whose members either themselves. It was at t his point that the Danish scholar. however. he came to accept the larval nature o f cercariae although he continued to use generic names for them 26. These views were modified by the Ger man zoologist. He the n went on to show. hepatica 91. Unfortunately. He noted further that whe n cercariae were released they showed a strong inclination to leave the water and climb up onto foreign objects. and suggested that they could be the intermediate forms of F. into what redia it was converted. A few days after placing them in his breedin g vessels. Cercaria echinifera was converted very rapidly in the intestine of warm blooded animals and slowly in that of cold-blooded species into Distoma echinifera. whether their offspring were tailed or tail-less. von Siebol d expressed the opinion that encysted cercariae must migrate. During studies of the molluscan fauna of the Swabian Alps. that they might encyst on grass in order to be ingested by sheep. When Küchenmeister came to review the probable life cycle of F. especially in the lungs. he ran out of snails with which to continue . and had two eye spots and a head sucker. in 1875. Later (1858). that although it was still unknown how th e miracidium became metamorphosed. flava became transformed into Monostomum flavum of finches and sparrows 87. or whether the y encysted themselves. Algernon Thomas turned his attention to the problem. La Valette de St. la Valette de St. needed to b e transmitted with the bearers on or in which they were encysted into other hosts.e.110 A History of Human Helminthology remained obstinate. He speculated. truncatula) in the Dresden Botanical Gardens. however. and when Rudolf Leuckart in German y finally began to have some success with his endeavours. They had the form o f small tubes. or possibly by drinking contaminated water 46. Leuckart had tried in vain to infect the most frequently encountered local snails with miracidia of F. 31 before they could mature 76. For many years . infected themselves with encysted worms by devouring infected snails hidden in grass or vegetables. i. he foun d small snails which he thought were Limneus minutus (= L. but without cilia. Diesing in his major work of 1849-1851. He thought that there was little doubt that these organisms were related to F. Immediately after the appearance of Steenstrup's book. it seemed likely that herbivores and omnivores. still considered cercariae to be adult trematodes and erected a suborder for them25. that when certain encysted cercariae wer e ingested. they failed to develop. Near the end of the summer of 1879. where the rediae lived. therefore. Thus . George87 and Pagenstecher 65. Thus. This was the scene in 1880 when the young Englishman. hepatica in 1855 he speculated. George provided important information when he showed that if tailed. hepatica miracidia. he found that some snails were cover ed with small parasites which were also to be found in the viscera. he found rediae in the livers of Limnea (= Lymnaea) truncatula. David Weinland. In this view he was supported by de Filippi . non-encysted cercaria e were administered to experimental animals. the larvae escaped in the stomach and matured in the gut. hepatica. therefore. while their contents consisted of clear cells which were beginning to proliferate. and C. Systema Helminthum. including humans. hepatica in L. George Rolleston. Consequently. In fact. he convinced himself that the snail s were really young L. his final paper being published in October of that year 50. Thomas took up the challenge and showed first that eggs of F. There he examined the fauna. almost simultaneously wit h Thomas's second report in the Journal of the Royal Agricultural Society o f England. who had earlie r postulated that the black slug. he at first believed incorrectly that F. The Roya l Agricultural Society of England provided funds for an investigation of th e problem. Limax cinereus. hepatica rediae contained tail-less larvae 49. particularly regarding t ransmission of the infection. Arion ater. Thomas. hepatica in England. further. Succinea amphibia. but without success. hepatica. pereger which he had already failed to infect wit h F. A major outbreak of liver rot in 1879-1880 had killed more than three million sheep in Britain. however. and in 1882 detailed the development of F. the former worm metamorphosed into a sporocyst. hepatica when they were half-grown or mature. He traced the development of miracidia into rediae containing 5. he had been unable to characterize them in any detail 48. The results . Arion hortensis. professor of anatomy and physiology at Oxford University. that the released miracidia lived for only about eight hours in water. hepatica miracidia might only be able to develop in very young snails of this species. who had just bee n appointed demonstrator in biology at the University Museum be given the task. Concurrently with Leuckart and quite independently of him. trigonocephalum developed in the snails Bithynia tentaculata and Paludina species. Thomas was aware that similar embryos of Distoma nodulosum and D. and the latter helminth changed into a redia.Fascioliasis 111 his experiments. He declined because of ill-health bu t recommended instead that his former pupil. Thereupon. but by the time of his report in December 1881. hepatica. In the interim. although some eggs continued to hatch over weeks or even months 83. that a species of mollusc was likely to be the intermediate host of F. hepatica miracidia. was the intermediate host. respectively. wa s approached to investigate the problem. he expose d experimentally "Arion ater. hepatica would not develop when maintained at internal body temperature (37 oC) or at the lower temperatures obtaining during an English winter. however. in great detail in the middle of 1880. He then realized his mistakes. He assumed. This led him to the idea that F. and so began to visit a large number of farms near Oxford where there had been severe outbreaks of fascioliasis in 1879-1880. He believed this t o be proven in the summer of 1881 when he was able to infect hundreds of young snails thought to be L. He observed. Thomas was researching the life cycle of F. Planorbis marginatus. Limax agrestia.8 offspring. Limnaeus pereger and Limnaeus truncatulus"83 as well as some small crustacea to F. the miracidia developed fully within two to thre e weeks. both ultimately giving rise to cercariae. pereger with F. When the eggs wer e kept at 23-26 oC. therefore. truncatula. he decided to tackle the problem from anothe r angle. In these hosts. particularly the snails. and a paucity of the molluscs plagued him again in th e following year. the identity of these worms remaine d uncertain. he was able to observe the habits of these cercariae. truncatula. upon which they fed. the absence of an epidemic of liver rot in sheep near Oxford that year consoled him somewhat and convinced him that he must be on the right track. a tiny L. hepatica miracidia and was immediatel y successful: The snails were speedily found to have afforded a suitable place for the further development of the embryos.112 A History of Human Helminthology were tantalizing but inconclusive. he had reasoned that two species of snails likely to be intermediate hosts were Lymnaea pereger and L. Nevertheless. balls of cells multiplied and were transformed int o rediae. Since no-one at that time knew what th e cercariae of F. although it was still not clear what form they would take. however. no appropriate snails could be found. He observed that once in the snail: the embryo undergoes a metamorphosis. and of those examined up to the present time all have proved to be infected. In July of 1882. On 22 December 1880 he found in a field at Wytham. the rediae were approximately 1 mm long by 0. each with its own pharyn x and intestine. he tried onc e more to infect these snails experimentally. especially plants. He exposed them to F.84 This organism was not a redia. Thomas's source of snails had dried up and such researche s had to await the next season. floods in the rive r Isis (Thames) at Oxford result ed in the appearance of vast numbers of L. hepatica looked like. which Thomas found in the pulmonary membrane of the mollusc. especially the liver. In the meantime. 84 Thomas was then able to follow the devel opment of larvae within the snails. Th e following year (1881) proved to be one of intense disappointment. often containing as many as 80 embryos. and the wound caused by its forcible exit immediately closes up. truncatula. These molluscs were two of the eight species of snails on the Faroe Islands where fascioliasis wa s very common. Accordingly. but a sporocyst or brood-sac in which redia e would be formed. It loses the external layer of ciliated cells and changes from the conical to an elliptical shape. Within the sporocy sts. pereger was the only aquatic pulmonate snail on th e Shortland Islands where liver fluke also occurred. The only way to be sure was by experimental infection of snails. He found that they encysted on surroundings objects . He found that when a redia was fully formed: it breaks through the wall of the sporocyst. truncatula which was infected with a redia containin g peculiar tadpole-shaped cercariae. By seven weeks .2 mm in width an d contained up to a score of "germs" or " spores" in various stages of development. for they were very activ e and migrated from the pulmonary chamber to various tissues. and there remaining germs continue to develop. he could find cercariae within the rediae. and speculated that sheep might be infected wit h F. hepatica by ingestion of grass contaminated with these cysts. and L. 84 These rediae were much more dangerous to the snail than the rather iner t sporocysts. In contrast to Leuckart' s . Never theless. but by this time. By 31 days afte r infection. Despit e scouring the countryside. truncatulus which I have infected have proved to contain larval trematodes. and remained viable for up to two months. The kid died within 20 hours of feeding. The f irst animal was infected on 23. Thomas' s second report84 and Leuckart's final paper50 both came out in October 1882 . encyst on grass and then be ingested. hepatica. still recognisable by the eye-spots and papilla as belonging to F. another ten years were to elaps e before the Brazilian. proved that infection was acquired by in gestion of cysts containing metacercariae. Be that as it may. these cercariae and rediae appeared to be identical with those he had seen in the snail collected from the farm at Wytham two years before. Thes e cercariae encysted rapidly as soon as they found support. Lutz was working in Hawai i where he was the Director of the Leper Hospital in Honolulu. It was found dead one month later and autopsy revealed numerous small cavities filled with blood clot in the live r parenchyma: 29 flukes ranging in size from 5-9 mm were recovered from this . Lutz observed in 1892 that snails infected with Fasciola only liberated cercariae when they were damaged or dead. 24 and 27 December 1891 with about 60 cysts. Adolfo Lutz. The rediae in which they occurred were closely similar to those I have found throughout this examination of the snails I have infected with embryos. He infected a kid. Indeed. whether a plant o r some other material. as Leuckart favoured.86 reviewing his findings and comparing them with those of Leuckart. or as he believed more likely . He ended his paper by indicating that it was still necessary to elucidate the manner in which sheep were infected wit h cercariae. hepatica within the same snail. and calculated that a single fluke might give rise to over 1. The reasons for his apparent lack of success were not apparent until Ssinitzin discerned the pathway o f migration in the body of young worms in 1914. all the specimens of L. What was more. hepatica. Although h e published his findings as referring to F. Moreover. and all were completely free from larval trematodes. Thomas then wrote two further papers 85. but generated rediae instead. Despite Thomas's confident anticipation that he would soon be able to provide the answer to the last-posed question. clearly belonging to one and the same zoological species. gigantica 2. the findings are equally applicab le. probably because it was weaned too early. and as a preliminary precaution a number of snails of the same gathering as those submitted to infection were examined.84 Furthermore. He had more luck with his guinea pigs. and in the same snail with these rediae were sporocysts. Leuckart had also tried to infect rabbits but was unable to find any worms. H e concluded that: There can be no doubt that the cercariae I found really belong to the liver fluke.000 cercariae. He noted that this could occur either by consumption of mollusc s containing cercariae. cercariae might swim about. each cer caria was endowed with a long tail. a piglet and three guinea pigs with numerous cysts of different ages. he found as many as four generations o f larval F. In t he interim. Thomas observed that rediae sometim es did not produce cercariae.Fascioliasis 113 assertion of the previous year. it has since been suggested that the species he studied was in fact F. and worms could not be found in the piglet bec ause its stomach was too full. therefore the sheep cannot live" 15.. And this bad herb does not rise.. He found it necessary to explain that the reason why sheep died was because "the liver is one of the three principal places where life lies. Redi emphasized the biliary location of worms further in 1684 69 as did Bidloo in 1698.. and here they may be said to swarm. liver disease. Jean de Bri e (1379) ascribed a major role to the herb. Finally. In the small gall-ducts they lie longitudinally. he comprehended the connection between flukes. Similar findings were obtained with the third guinea pig 52. jaundice and ascites: whane thou hast kylde a shepe his belly woll be full of water yf he be sore rotten: and also the fatte of the flesshe wolle be yellowe if he be rotten and also and thou cut the lyver therin wyll be lytell quykena lyke flokes and also the lyver will be full of knotts and whyte blysters yf he be rotten. 15 de Brie believed that this damage was then compounded by the worms which were generated and ultimately destroyed the entire liver. Fitzherbert (1523) described the morbid anatomy of infected sheep ver y graphically. in describing an epidemic in cattle in Zeeland. In the second guinea pig. does not return to the throat of the animal as do other herbs but. Willius in 1674..... but that large numbers of flukes were also present in the biliary and hepatic ducts 92. In these parts the noxious animals are found in heaps and the places where they lie become hard and cartilaginous.. Shirai eventually proved that not only were cercariae non-infective. Thus.. contortions and sinuses in the part: and cavities which will be often found an inch and a half in diameter. tubes and channels wherein the gall is formed and collected.114 A History of Human Helminthology organ. Moreover.32 Many persons believed that the flukes were situated in the portal veins. though most commonly in the liver. but the cysts were not either until a period of at least twelv e hours had elapsed after encystment 74. The latter wrote that they are found: only (in) the vessels. wrote that not only were the worms in the branches of the portal veins. 1 8 flukes were recovered 32 days later. STUDIES OF THE MIGRATION AND DEVELOPMENT OF LARVAE AND PATHOLOGICAL REACTIONS IN THE DEFINITIVE HOST Initial conceptions as to the genesis of disease were confused. producing grievous swellings. John Faber in 1670 was apparently the first to state that liver flukes were located in the bile ducts28. the mode of transmission of the parasite from excretion of eggs in the faeces to ingestion of metacercariae had been determined. and sometimes rolled or curled up together. callosities. What remained to be demonstrated was the route of migration and the processes of maturation o f worms in the definitive host.corrupt(s).the liver. which had been fed with about 20 cysts. one of them being in the liver and the rest being located in the peritoneal cavity. "la dauve": La dauve is of such a nature that it adheres to and lives in the liver of the sheep or other beasts. 8 . I should penetrate into a blood vessel but I am too big for that. He put the reasoning behind his experiment in a very entertaining fashion a few years later: I am now a cercaria which has just emerged from its cyst and has found itself in the intestinal tract. They occurred especially near the surface of the liver. they burrow further. inf lammation and necrosis of the liver by worm toxins.. Thomas had seen flukes in the peritoneal cavity of a rabbit and had been told of worms in the mesentery and uterus of a sheep that had died of the rot. Leuckart advises me to look for the opening of the gall duct in the duodenum. Thus. but probably do not reach full development. In one of his experimental guinea pigs. In 1880. they may pass along beneath the peritoneum... they perforate the capsule and thus can reach the peritoneal cavity where they live perhaps for some time. Lutz (1892) made the same mistake.. but he failed to interpret it properly... Thomas made an observation which could have put him on the right path. but while I am listening to him I am transported far behind this opening and how can I. the logical assumption seemed to be that they reached that site via the opening of the bile duct into the duodenum. causing the destruction of the parenchyma as they proceed. Once the location of worms in the biliary tree was identified correctly.. Having reached the surface. the vast majority of young flukes were in the peritoneal cavity.. including distension. Leuckart made similar observations and also arrived at the same misconception. immature flukes. but he concluded erroneously that: the invading flukes soon go to the periphery of the liver and when the normal bile passages become too narrow.Fascioliasis 115 Bidloo further realized that the numbers of worms varied enormously: in one liver he recovered 870 worms plus ma ny fragments. and competition by the worms with the organs for nutrien t juices.pierce the peritoneum and set up perihepatitis.52 It fell to Dimitry Ssinitzin (also known as Sisintsin) in Moscow in 1914 to demonstrate what is generally accepted as being the true pathway of migration. He postulated a number of mechanisms b y which they might cause ill-effects. he was sent a liver which contained over 2 00 small.On me are poured smart. but his interpretation was exactly opposite to the actual route of migration..83 Furthermore. whereas in other livers he found but ten or twelve flukes.What am I to do? If I were smaller. In September of that year. For over 200 years this remained accepte d dogma. or.. in such a spacious hollow filled with moving food. find that commended spot? I do not accept .. destruction an d inflammation of the biliary passages following obstruction of the biliar y circulation by worms and their products. Thomas made the correct observations..through the soft parenchyma. Arrived at the surface of the liver. biting fluids from the digestive glands and I wish nothing more than to escape this horrib1e place. Dr. The young fluke on entering the liver by the duct appears to push its way onwards into smaller ducts where some remain whilst others penetrate the walls of the ducts and crawl forwards to the surface. By far the largest number were in the smaller branches of the bile ducts or in centres of destroyed hepatic tissue. He noted that: no flukes of any kind could be found in the larger ducts. Nevertheless. Suzuki in 1931 provide d confirmation in another manner. the n passed further into the biliary passages every day. RECOGNITION OF THE CLINICAL FEATURES IN ANIMALS Fitzherbert provided a masterly description of the clinical manifestations of liver rot in sheep. worms may live for at least nine years 3. a judge of the Court of Common Pleas. I hasten to conceal myself in any place. He freed young worms from their cysts b y artificial digestion then inject ed them directly into the abdominal cavity. penetrated into the liver parenchyma with the aid of hard. They then attached themselves to the surface of the liver by the mouth suction cap. but three patients have been reported with longlasting infections. I work my way into the bottom. paying particular attention to jaundice (best noted in th e eye).32 .. He noticed that they fed on erythrocytes during their travels and emphasized the large haemorrhages they left in their tracks behind them. To Sir Anthony Fitzherbert. he did not believe that th e former pathway was really relevant in natural infections. He then observed that they penetrated the intestinal wall and passed into the peritoneal cavity where they remained for up to two weeks. Final ly. suggesting that in humans. portal vein and bile duct of goats. the appearance of the sk in and the condition of the wool.take a lytell of the wole between thy fynger and thy thombe and pull it a lytell and yf it stycke fast he is sounde and yf it come lightly of he is rotten.116 A History of Human Helminthology this advice. rabbits and guinea pigs. The duration of infection is uncertain.. Ssinitzin's findings were confirmed in guinea pigs by Shirai in 1927 74 and then in rabbits by Krull and Jackson in 1943. between the folds of the epithelium and penetrate through the intestinal wall. they reached the larger branches of the biliary system and mature worms bega n to pass eggs two months or more after infection80. 79 Ssinitzin infected rabbits with metacercariae and found that the young worms had escaped from the cyst walls within two to three hours of reaching th e intestine. He claimed success for the portal but not the biliary routes. pointed spines. considering instead that some of the young worms penetrated the intestinal wall to enter th e abdominal cavity 82. and the strindes darke coloured than he is rotten: and also take the shepe and upon the wole on the syde and if the skynne be ruddy colour and drie thane he is sounde: and if he be pale coloured and watry than he is rotten. And if the eye be whyte lyke talowe. John: Take both your hands and twyrle upon his eye: and if it be ruddy and have reed strands in the whyte of the eye than he is sounde.. has traditionally bee n ascribed authorship of A Boke of Husbondrye published in 1523 but it wa s probably written by his brother. and began to cough. Examination revealed that his abdomen was distended with gas and that h e was intensely tender in the epigastrium. Soon after admission to hospital. hepatica 37. the case was described of a French naval officer who after three weeks of a pulmonary illness which included pain at the base of his right lung . 1879. paroxysmal coughing and slight haemoptysis. some subsequent commentators have believed that this worm was really F. he became febrile and developed increasing pain in the right hypochrondrium . jaundice was not a common feature. but the liver was rarely much enlarged. weight loss and right upper quadrant pain and tenderness of th e abdomen. the upper rectum was thickened and narrowed. fever. The liver was greyish-red and tense. a 52 year old labourer at Corfe Castle in Dorset. hepatica 38. this experience (in 1848) suggested to some commentators that fascioliasis might be acquired by migration of cercariae through the skin 46. gigantica. Finally. adult F. with sinus tracks opening into it. Englan d complained of vomiting and upper abdominal pain of two months' duration . This was said to be the first recorded case in which the parasite had been lodged in the lungs. the hepatic ducts were considerably thickened and enlarged and contained 26 fully developed F. Despite the severe complications which could occur. Many of them had transient episodes of urticaria. hepatica has been said to cause "halzoun" or oedema of the . Perhaps unexpectedly in view of the fact that flukes live in the bile ducts. 117 IN HUMANS One of the earliest detailed descriptions of subacute fascioliasis was recorded during the severe epidemic of sheep rot in Britain in 1879-1880. I n November. This was confirmed during a small outbreak of fascioliasis in six patients in England in 1958. surgica l exploration revealed the presence of an immature F. none of whom wer e jaundiced29. as in this patient. Naturally enough.Fascioliasis This description has hardly been improved upon since. hepatica 40. finally coughed up a living F. At post-mortem examination. diarrhoea. The dominant features in these patients were malaise. occurring in only three of sixteen patients reported up to 190227. Very infrequently. In 1895. and in a subsequent epidemic involving 44 people a few year s later in the same country39. His rectum became blocked transiently. Fistulous abscesses developed around the rectum and he died four month s later. but as will be discussed later. it was recognized that many infected people were either asymptomatic or had onl y minor symptoms. immature flukes have been found in ectopic sites. bu t was cleared and he passed a stinking slough 3x5 inches in size per rectum . One of the earliest recorded examples of this concerns a woman who presented i n 1848 with a painful sole which she had had for several months. then this assay was improved and used in a human patient by Servantie in 1921 73. He examined the carcasses of some of these sheep and found flukes in the biliary system. DEVELOPMENT OF DIAGNOSTIC METHODS For many years. no attempt was apparently made to examine the faeces microscopically for ova. despite the fact that it was well-known to veterinarians that eggs were common in the faeces of infected shee p. but evidence for . Chabert claimed to effect the passage of flukes with his empyreumatic oil 19. this was also first recorded by Ward 89. Martin and his collaborators found eggs in the bile in 1944 54. both by scratch testing and by intradermal injection. Subsequent putative remedies included extract of mal e fern. Skin tests.118 A History of Human Helminthology buccopharyngeal mucosa by becoming attached to the lining of the oral cavity when ingested45. Azar was unable to reproduce this when he fed infected raw liver to 92 volunteers 6. THE SEARCH FOR EFFECTIVE TREATMENT It is only in recent times that effective therapy for fascioliasis has becom e available. San Pedro Marti n de la Calle in the late 1880's (cited in4 ). Nevertheless. Many years ago. Indeed. The rar e patient passed flukes in the faece s or brought them up in the vomitus. The possibility of diagnosing fascioliasis serologically by a complement fixation test was first demonstrated in sheep b y Weinberg in 1909 90. were used by Morenas with the former technique being mor e accurate57. His patient remained undiagnosed for four months until it suddenl y occurred to Martin de la Calle that many sheep had been dying for the past few months from a disease called locally "con vulia". it is likely that this will become more common now that upper gastrointestinal endoscopy is bein g practised widely. The clue being thus obtained. he set abo ut looking for flukes in the patient's faeces. and that these sheep had many signs somewhat reminiscent of those present in his patient. carbon tetrachloride and thymol. Surprisingly. Küchenmeister (1855) despaired of treatment. A clue to the infection may be provided by finding an eosinophilia. a diagnosis of fascioliasis was difficult to prove. but eventually an adult fluke was passed after the patient had been treated with castor oil. the first person who diagnosed a patient in this way seems to have been Ward in 1911 89. bu t recommended that calomel and mineral waters or oil of turpentine with sulphuric ether be tried 46. antimony compounds. The first person who considered the diagnosis in and proved it in a living patien t appears to have been Dr. nothing was found at first. although convincing evidence for this was not pre sented5. Cornelius Gemma wh o ascribed it to a manifestation of divine justice as were earthquake. who. The other rotted with delicious feed. It gradually became clear that infection was most likely to occur when sheep and other animals were fed on moist ground in warm weather. which the sheep like very much to eat. Than baits to fish. chloroquine was evaluated. green leaf that is called la dauve. Bithiniol was thought to be of value by Yoshida and his collaborators (1962) who used it in two patients 93. When as the one is wounded with the bait. flood and pestilence35.Fascioliasis 119 the efficacy of these drugs was lacking. Firstly. Kouri and Arenus introduced treatment with emetine in 1932 45 and this became adopted widely even though no controlled trials verified its efficacy . but which is very harmful and damaging to them. but it failed to cure the infection 29. Secondly. This drug was also claimed to be effective b y Ashton and colleagues. having described several grasses called "sperewort". In 1562. he showed that eggs . but could happen upland if there was sufficient moisture. round. This episode was followed by a large outbreaks in Holland i n 167492 and again in Germany in 168 3. it has been shown that praziquantel is effective in fascioliasis 72. Thomas (1881-1882) made a number of observations which helped to clarify the epidemiology of this infection. Again. Recently. he defined the environmenta l conditions necessary for ripening of the eggs. This was described by the Dutch physician and astronomer. UNDERSTANDING THE EPIDEMIOLOGY Jean de Brie in the fourteenth century made an epidemiological observation of the profoundest importance by linking the acquisition of infection to feeding animals on certain types of pasture at particular times of the year: The good shepherd should be extremely careful in the month of March not to lead his animals to pasture in marshy regions that are low and damp for there grows a very dangerous herb with a small. Subsequently. and yet more dangerous. 15 These points were expounded 150 yea rs later by Fitzherbert. In his studies on the transmission of fascioliasis . or honey-stalks to sheep. a very severe epidemic of sheep rot broke out in Holland. "penny grasse" and "myldew e grasse" remarked that "All manner of grasse that the lande flode ronneth over is yll for shepe" 32. This was most probable in low-lying marshes and swamps. The problem was so widespread and so well-known that Shakespeare alluded to it in his play "Titus Andronicus" (Act 4 Scene 4): I will enchant the old Andronicus With worms more sweet. good results were claimed i n a small number of patients treated with metronidazole 59. it was recognized that fascioliasis was rare in humans 4. they remarked that "we can throw no light on the question. It was now clear that epidemic s were common in wet years because moisture both enhanced the development of F. Fourthly. it was said that only 28 cases had been recorded in the literature up to that time. After discounting this as a possibility. With the demonstration of Simonds (1850) that feeding F. England in 1958-1959. thus prolonging the period of transmission. Nevertheless. for the patient had not been in the habit of eating sheep's livers . Despite the ravages of rot in sheep. studies have defined the species of Lymnaea and related genera that are intermediate hosts of this parasite in different regions of the world. hepatica eggs and favoured the multiplication of molluscan intermediate hosts. how the patien t contracted the disease" 40 but did mention that "he frequently ate th e watercress" 40. Militating against this. thi s possibility was in the back of t heir minds when Humble and Lush in 1881 discussed how their patient had become infected. his and Leuckart's discovery that certain speci es of snails were the intermediate host made the epidemiology of fascioliasis comprehensible. or by drinking polluted water. hepatica eggs did not result in infection. It was shown even more dramatically in a larg e outbreak in Monmouthshire.000 eggs. It subsequently became accepted that infection could be acquired by eating plants contaminated with cysts. although it must be said that man y hundreds of such infections have since been reported.120 A History of Human Helminthology continued to hatch over weeks or months. was the fact that environmental conditions generally prevented the majority of miracidia an d cercariae from finding their intended hosts. he confirmed that Weinland' s observation of cercarial cyst formation on grass 92 was applicable to F. he indicated that outbreaks of fascioliasis in sheep wer e associated with similar epidemics in rabbits and that these animals greatl y facilitated the dispersion of ova. England in 1968-1969 in which 44 patients were infected. by 1915. Thirdly. perhaps by ingesting infected snails. all of whom admitted to have eaten watercress from the same be d . particularly watercress ( Nasturtium officinale). The potentia l magnitude of transmission was emphasized by their calculations that eac h fluke produced at least 40. and thus helped to explain the mod e of acquisition of infection 83. Finally. Sheep were likely to be infected by eati ng grass contaminated with cysts. hepatica. During this century. it became apparent that the dangers of such a practice were not at all that great. The role of the former wa s emphasized when a small outbreak of fascioliasis occurred in six patients in Hampshire. and that a single miracidium might generate over 1. and with the delineation of the life cycle by Thomas and Leuckart (1 881-1882). all of them were in the habit of eatin g watercress frequently29.84. however. Indeed.000 cercariae. There was considerable discussion for many years as to whether it was safe for humans to eat the flesh of sheep with this infection. and possibly by drinking adulterate d water. then had coughed up a fluke 2. Further. Brazil published an account of a French naval officer who had recently been in Senegal and who had presented with fever and haemoptysis. infected livers disposed of. gigantica infection in a child in Tashkent. USSR. OTHER SPECIES OF FASCIOLA F. 121 THE EVOLUTION OF PREVENTIVE AND CONTROL MEASURES The possibility of preventing fascioliasis in sheep has been known for mor e than 600 years. Thomas amplified preventive measures by recommending that infecte d sheep be destroyed. The diagnosis was based only upon the appearances of eggs found in th e faeces67.Fascioliasis which also was located near some infected cattle and sheep 39. he emphasized the value of draining the land and destroying snails with a dressing of lime or with salt83. gigantica. In 1895. and manure from infecte d sheep be collected and eggs hindered from developing by the addition of coal tar or by being spread over. According to Brumpt16. Railliet considered that it was the liver fluke. GIGANTICA The adult fluke was discovered in the liver of a giraffe and named Fasciola gigantica by Spencer Cobbold in 1855 21. . led to repeated calls for education of the public concerning the dangers of eating wild watercress. Fitzherbert (1523) emphasized this. The life cycle of this parasite and the pathology and clinical features it induces parallel those of F. There have been differences of opinions as to the identity of this parasite. recommending that the sheep "may nat well be lette out of the fold tyll the sonne have domynacion to drie them away" 32. adequat e chemotherapy of infected animals and t he introduction of newer molluscicides. In 1927. F. To these measures were added during this century. Understanding the epidemiology and the frequent incrimination of water cress as the vehicle by which human infections were acquired. hepatica var augusta while Raphael Blanchard identified it as F. and recommendations that watercress be grown commercially unde r controlled conditions. The first clearcut case of fascioliasis gigantica was reported b y Codvelle and his colleagues in 1928 22. but different species of snails are the intermediate hosts. de Gouvêa in Rio de Janeiro. dry. de Brie in 1379 concluded his dissertion on rot in sheep b y reminding his readers that "the s hepherd should take care not to lead his sheep near marshy places where la dauve grows all summer long" 15. Pigoulewsky described F.5 cm long 38. well-drained ground. hepatica. 1798 9. American Journal of Tropical Medicine and Hygiene 13: 582-583. London.122 A History of Human Helminthology REFERENCES 1. éditeurs. Paris. Skrivter af Naturhistorie-Selskabet Kjøbenhavn 1: 26-64. 1964 7. John Bale. 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Miscellanea Curiosa Sive Ephemeridum Medico-Physicarum Germanicarum Academiae Naturae Curiosorum (1675-1676). DC . 1978 KHOURY A. pp 1267. 39. Ein Lehr. but really written by John. Publication 2830. Archives de Parasitologie 9: 78. Bibliotheca Italiana. Mathematische-naturwissenschaftliche Klasse 31: 239-290. British Medical Journal ii: 502-505 . Distomum hepaticum beim Menschen. Wilhelmum Braumüller. 180-1802 KEAN BH. 1837 Partly translated in 43 DAVAINE CJ. Qui est de quadrupedibus viviparus. 24. Classic investigations. Historiae animalium liber I. causis. pp 1003. pp 245-252. Wiener klinische Wochenschrift 15: 772-776. Fascioliasis . Paris. 28. pp 225. MOTT JE. Translated in 43 LEUCKART R. French summary. Opera posthuma. 63. Pensée Médecine d'Usbekistane. Neue Schriften der naturforschenden Gesellschaft zu Halle 3: 1-128. 59. 166-199. 1881. two volumes. 48. Partly translated in 43 MALPIGHI M. pp 68-99. non marinorum. . oder Naturbeschreibung der Zerkarien un d Bazillarien. Beitrag zur Infusorienkunde. 1831 MORENAS L. species. Novae observationes de entozois. 69. 67. genera. 49. Zweite Mittheilung. secundum. Zur Lebensgeschichte desDistoma hepaticum. 1857 van LEEUWENHOEK A. BABOUOT P. pp 135. two volumes. classes. pp 160. On animal and vegetable parasites of the human body. pp 257-252. diagnosis and treatment. Vol. 1857 PALLAS PS. Part of a letter from Mr. Isis (Oken's). pp 177. Piero 47. Firenze. tenth edition. 60. Systema naturae. 66. LE ROY. Holmiae. Cited in 77 PAGENSTECHER HA. Experiments on the generation of insects translated from the 1688 edition by M Bigelow. Animal parasites belonging to the group entozoa. 65. 56. (Un cas de Fasciola gigantica Cob chez un enfant Usbék en Vieux Tashkent. auctore Dr Fr Chr H Creplin. 50. Distomiasis in man. Vermium terrestrium et fluviatilium. p 131. Carlo Dati. ordines. Seltsame Lebens. Lugduni Batavorum. 58. Zur Entwickelungsgeschichte des Leberegels ( Distomum hepaticum). 1943 MÜLLER OF. Les réactions d'allergie cutanée dans la distomatose humaine àFasciola hepatica: cuti et intra-dermo-réaction. Jena. Opencourt Publishing Co. A manualof their natural history.und Tropen-Hygiene 32: 511-512 . Un nouveau cas de distomatose hépatique: diagnostic précoce par le tubage duodénal. . 1927. L Salvii. Heidelburg. succincta historia. 1928 REDI F. Helminthologischer Beitrag. 55. 61. 1760 PIGOULEWSKY SW. 53. 1773 NIK-AKHTAR B. pp 268. Zoologischer Anzeiger 5: 524-528. BOURCART N. 1698 MARTIN R.) In Russian.und Todesart eines kleinen bisher unbekanntnen Wasserthierchens. Abteilung originale 11: 783-796. locis. synonymis. Zur Entwickelungsgeschichte des Leberegels. oder Der Menschen im Leben und im Staate. 1892. pp 452.. Journal of Tropical Medicine and Hygiene 80: 179-180. pp 187. a seipso scripta. Report of four cases. Abstracted in. seu animalium infusorium . Angezeigt und mit Bemerkungen begleiter von Dr E Mehlis. Republished in German in Archiv für Schiffs. Centralblatt für Bakteriologie und Parasitenkunde. BG Teubner. two volumes. 64. 68. 51. Chicago. Bulletin de la Société de Pathologie Exotique 37: 359-363. Londini. G Reimer. pp 486. 1909 REDI F. 1668. 1704 LEUCKART R. 54.124 A History of Human Helminthology pflanzischen Parasiten des Menschen. cum characteribus differentiis. Metronidazole in fascioliasis. 57. 1817 von NORDMANN A. 52. Lancet ii: 1340-1341. Volume 1. 1882 LEUCKART R. The Sydenham Society. Zoologischer Anzeiger 4 : 641646. per regna tria naturae. Osservazioni intorno agli animal viventi che si trovano negli animali viventi. 1977 NITZSCH CL. Quibus pra efixa est vita. Dissertatio medica inauguralis de infestis viventibus intraviventia. Antony van Leeuwenhoek concerning worms observ'd in sheeps livers and pasture grounds. London. 1882 LINNAEUS C. 1855. Trematodenlarven und Trematoden. Zur Entwickelungsgeschichte des Leberegels. A et J Churchill. 1758 LUTZ A. Oder Encyclopädisch e Zeitung. In. pp 823. pp 59-61. pp 56. Kilian. Havniae et Lipsiae. helminthocorum et testaceorum. 1832 OKEN L. Georgia. Esperienze intorno alla generazione degl'insetti. Archiv für Naturgeschichte 1: 80-119. Mikrographische Beiträge zur Naturgeschichte der wirbellose n Thiere. Berlin. . 1807 NITZSCH CL. Comptes Rendus Hebdomadaires des Séances e t Mémoires de la Société de Biologie 137: 563-565. Philosophical Transactions of th e Royal Society 24: 1522-1527. Leipzig. 1944 MARTIN de la CALLE SP. 62. Cited in 13 OKEN L. SUREAU B. translated by E Lankester. TABIBI V. 1890 MEHLIS CF. Infusoria . 281-286. 1. 1921 74. Abstracted in British Medical Journal ii: 1001-1002. Braun Schweig. Om Fortplantning og Udvikling gjennem Vexlende Generation s Raekker. 1845 82. 71. 1784. 1854. Holmiae. Lectionibus publicae de vermibus intestinalibus imprimis humanis qua s habuit in musaeo rev. Neue tatsachen über di Biologie der Fasciola hepatica L. translated by T H Huxley. 1684. or. 1842. 1882. qua s habuit in musaeo rev. von SIEBOLD CT. CHRI TIE AJ. Comptes Rendus Hebdomadaires des Séances et Mémoires de la Société de Biologie 84 : 699. The Ray Society. Delectus oposculorum medicorum. 1911 . 78. Journal of the Royal Agricultural Society of England 17: 1-28. nat. 6: 511-523. 1835 e. no 12. Berlin. SSINITZIN DF. fifth edition. imprimis humanis.Fascioliasis 125 Matini. 1844 77. 2: 650-676. Recherche de la déviation du complement dans la distomatose humaine. Journal of the Royal Agricultural Society of England 18: 439-455 . 1882 86. especially on the determinatio of the first intermediate host and some experiments n with larvae freed from their cysts artificially. In. Tokyo. 1857 89. 1926 80. Kjøbenhavn. Handwörterbuch der Physiologie mit Rücksicht au f physiologische Pathologie. 1914 81. Leipzig. 1880 79. Naturkundinge Verhandelingen van de Hollandsche Maatschapij der Wetenschappen te Haarlem. Successful treatment of severe S infection with Fasciola hepatica with praziquantel. Quarterly Journal of Microscopical Science. Methods I have followed in my research. John Murray. Abteilung originale 74: 280-285. pp 132. British Medical Journal i: 931-935 . WAGENER GR. acad. On the tape and cystic worms with an introduction on the origin of intestinal worms. R Wagner (Editor). In. SHIRAI M. Zentralblatt für e Bakteriologie. J P Frank . 23: 99-133. THOMAS AP. Ludensis d xviii Martii et seq. GEORGE A. Partly translated in 43. Ticini. SISINTSIN DF. pp 88. Parasitenkunde und Infektionskrankheiten. Lectionibus publicae de vermibus intestinalibus. 85. Über die Band. Report on experiments on the development of the liver fluke ( Fasciola hepatica). Journal of Parasitology 13 : 84-86. STEENSTRUP JJ. Second report of experiments on the development of the liver fluk e (Fasciola hepatica). 1927 75. pp 55. SERVANTIE L. London. pp 100. causes.. On the alternation of generations.und Blasenwürmer nebst einer Einleitung über di e Entstehung der Eingeweidewürmer. RETZIUS AJ. Beiträge zur Entwickelungs-Geschichte der Eingeweidewürmer. 1786 . The biological observation on the cysts ofFasciola hepatica and the route of migration of young worms in the final host. WARD GR. 1784. Hepatic distomiasis (sheep rot) in man. en saeregen Form for Opfostringen i de lavere Dyreklasser. (Researches into the life history of Fasciola hepatica and its distribution in Formosa. 9:1-92. Ludensis d. 1790 72. SCHIAPPACASSE RH. la VALETTE de St. THOMAS AP. pp 244. 1931 83. The rot in sheep. CA Reitzel . pp 112.) Taiwan Igakkai Zasshi volume 30. The life history of the liver fluke (Fasciola hepatica). Journal of Infectious Diseases 152 : 1339-1340. pp 76. Helminthologische Beiträg Archiv für Naturgeschichte 1: 45-84. The rot in sheep. von SIEBOLD CT. Th e Sydenham Society. or the life history of the liver fluke. acad. W Engelmann. pp 38. nat. xviii Martii et seq. RETZIUS AJ. pp 115. 1985 73. In Japanese. treatment and prevention. 1882 and Lancet ii: 849. 70. Firenze. 1857. MOHAMMADI D. translated from the German version of CH Lorenzen by G Busk. the propogation an d development of animals through alternate ge nerations: a peculiar form of fostering the young in the lower classes of animals. bound with volume 2 of F Küchenmeister's Manual of Parasites. Symbolae ad trematodum evolutionis historiam. 1881 84. new series. SUZUKI S. Parasiten. its nature. THOMAS AP. Nature 26: 606-608. 1883 87. 76. SIMONDS JB. THOMAS AP. with English summary 30: 97-100. von SIEBOLD CT. London. 1882. London. 1855 88. Scientific Reports of the Government Institute of Infectious Diseases. pp 568. 1962. Recherches des anticorps spécifiques dans la distomatose et la cysticercose. WILLIUS JV. Landmarks in fascioliasis _________________________________________________________________ First recorded reference to worms in sheep by de Brie. Stuttgart. NISHIDA K. and diseases. and the treatment with bithiniol). YOSHIDA Y. 1875 92. FUJISAKA K. YAMASHIKI Y. Malpighi and Bidloo) 1882 Leuckart and Thomas described independently the development of miracidia through to cercariae in the snail. Lymnaea truncatula 1892 Lutz demonstrated that adult worms developed after ingestion of encysted metacercariae 1911 Ward diagnosed human fascioliasis by finding eggs in faeces 1914 Ssinitzin demonstrated the pathway of migration of flukes in the definitive host 1985 Schiappacasse and colleagues reported that praziquantel was effective in human fascioliasis ___________________________________________________________________ 1379 . NAKANISHI Y. their breeds. Vernichtung des Viehstandes auf Abrahamstrup in Seeland durch Blasen würmer. Bartholinus. EBARA S. TANAKA A. 5 volumes. In Japanese 94. WEINLAND D. London. MIYAKE K. WEINBERG. (Two cases of human infection withFasciola sp. Die Weichthierfauna der schwäbischen Alp. Sheep. Comptes Rendus Hebdomadaires des Séances et Mémoires de la Société de Biologie 66 : 219-221. management.126 A History of Human Helminthology 90. Acta medica et philosophica. who also linked infection with feeding animals in certain types of pastures at particular times of the year 1523 Fitzherbert gave an accurate clinical description of fascioliasis in infected sheep 1670 Faber observed that worms were located in the biliary tree 1690 Bidloo discovered eggs and recognized that the worms were hermaphroditic 1758 Linnaeus named the worm Fasciola hepatica 1760 Pallas gave the first detailed account of human infection (earlier allusions had been made by Borel. 1837 Table 4. London. ISHIKAWA T. Library of Usefu l Knowledge. Th. p 101. 1909 91. Japanese Journal of Parasitology 11: 411-420. Hafniansa. YOUATT W. 1673-1680 93.1. In. Distoma Buskii Distribution: Asia. pigs. Definitive hosts: humans. People become infected by peeling off the outer covering of the plants with their teeth before swallowing the raw nut. but were like the Distoma lanceolatum in structure. (dogs) Major clinical features: diarrhoea. found 14 flukes in the duodenum.Chapter 5 Fasciolopsis buski and FASCIOLOPSIASIS. which were not present in the gall bladder or bile ducts: were much thicker and larger than those of the sheep. They resembled the Distoma hepaticum in shape. On animal and vegetable parasites 127 . George Busk. The metacercariae excyst in the duodenum. SYNOPSIS Common name: giant intestinal fluke Major synonyms: Distoma crassum.e. 20-75 mm in length. attach to the small intestinal wall and mature in about three months. 8 This discovery was cited again in 1857 by ER Lankester in appendix B to his translation of Küchenmeister's textbook. The miracidium becomes a sporocyst which passes through first and second generation rediae to produce cercariae after a few weeks. being not branched. Diseases of the Liver. being from an inch and a half to near three inches in length. The ova develop in water over 3-7 weeks then each miracidium escapes and invades snail intermediate hosts of the genera Segmentina and Hippeutis. based upon informatio n supplied by Busk. This finding was not reported until 1852 when. It was noted that these flukes. They produce eggs which are passed in the faeces. a sailor from the eastern part of India) who had died in the naval hospital Dreadnought in Greenwich. especially eastern Asia Life cycle: The elongate-ovoid hermaphroditic worms.5-5 mm in thickness live in the small intestinal lumen attached to the duodenal and jejunal mucosa. England. the double alimentary canal. 8-20 mm in breadth and 0. praziquantel DISCOVERY OF THE ADULT WORM While performing in 1843 an auto psy on a Lascar (i. the English surgeon. The cercariae emerge from the snail and encyst on aquatic vegetation including caltrop and water chestnut. and the entire space between it towards the latter part of the body being occupied by the uterine tube. dichlorophen. it was described briefly by George Budd in his book . as in the latter variety. abdominal pain and urticaria in heavy infections Diagnosis: demonstration of eggs in faeces Treatment: hexylresorcinol. I have called it. however. After speculating about the possible life cycle of th e parasite. the naming was not accompanied by an adequat e description. Cobbold therefore asked Busk to suggest a ne w name. This was adopted by Cobbold when he redescribed the worm in his Synopsis of the Distomidae communicated to the Linnean Society in London in June 1859 and published in its journal in the following year10. were misled by the inaccurate original description of the uterine coils and transferred the worm to the genu s Dicrocoelium. i. They were referred to Cobbold who treated them with aloes and asafoetid a without any improvement. This was to cause confusion subsequently. The parasite passed into the hands of Josep h Leidy who exhibited it at the Academy of Natural Science in Philadelphia i n October 1873. Cobbold himself used the former term in his original description. buski when he described the worm passed by a 35 year ol d . He corrected the error 18 years later. Cobbold considered the name invalid on the ground that Lankester had not provided a sufficien t description of the parasite. had sent another worm to Professor Gross in the Unite d States of America. merely to commit another when he equated it with F. with some authors calling the worm D.e. This nomenclature was rejected by C obbold for the same reason that he had set aside D. J Poirier began the fashion of giving new specific names to variant specimens of F. When Cobbold showed them to Busk. Distoma Buskii. Cobbold's redescription w as based on one of Busk's original flukes which had been kept in the museum of the Royal College of Surgeons i n London. magna 21. Dr JG Kerr. the name Distoma crassum had already been used in 1836 by von Siebold for a fluke found in a house martin. crassum in his textbook in 1863 23. Eventually. He subsequently sent the worm to Leuckart who concurred wit h Cobbold's view and described it as D. In 1887. however. The parasite was not recognized again until the northern spring of 1874. He added that at one time. objected to this designation. however. A missionary and his wife who had been resident in China for about four year s consulted Dr George Johnstone in London concerning persistent diarrhoea . the founder of the Hospital for the Insane i n Canton. Leidy described its external morphology but said nothing of its internal organization and misdi agnosed it as Fasciola hepatica 20. a four year old English girl ha d passed nine of these worms. Distoma crassum (derived from the Latin "crassus" meaning "thi ck" or "gross"). China. remarking that it had been vomited by a 15 year ol d Chinese boy. twelve worms were expelled spontaneously. Meanwhile. crassum Cobbold. after the name of its discoverer.19 Busk. M oreover. he went on to say that: In the absence of any other distinguishing name for this species. To complicate matters more. Weinland and also Davaine14. crassum Busk and others referring to it as D. buskii. and the latter thereupon proposed the appellation.128 A History of Human Helminthology of the human body. "he at once recognised them as referrable to the species he had long ago discovered" 11. hepatica. Poirier concluded that the parasite must have come from the bile ducts and named it D. spelling the specific name with one "i" 30 instead of with two (buskii) as in the original of Lankester. He concluded that: the parasite showed great variation in morphology but withal such gradation in variation as to justify including the forms now described as F. an eight year old girl in Hong Kong vomited a fluke. another Laskar from Calcutta was admitted to the Seaman's Hospital in Hamburg. China. F. He was supported in this view by Odhner 30 but contradicted by Ward 38 and by Railliet and Henry34. fülleborni 35. spinifera 7. and which ha d been sent to him by Father Rathouis in Shanghai. and E Rodenwaldt. this species had been transferred to another genus by Odhner in 190230. it was brought to DM Heanley by Dr Kwan King-Hung. goddardi. Finally. and believing erroneously that F. buski that had been macerated by th e action of gastric juices before being vomited 22. 1. Ward's opinion was based on a study of 11 specimens obtained from two cases by FW Goddard in 1907 and forwarded to him by Dr WH Jeffreys of Shanghai. buski did not have cuticular spines. named it F. with a provisional diagnosis of typhoid fever. buski. rathouisi 33. Odhner improved on the description of the worm and transferred it to the genus Fasciolopsis that had been erected by Looss in 1899 25. All this confusion and proliferation of names was brought to an end in 1919 by FW Goddard of the Christian Hospita l in Shaohsing. He examined flukes in the Zoological Museum in Copenhagen tha t were contained in two glass jars dated Dec. In 1908. In 1909. He passed several flukes in his faeces. goddardi in the species F. proposed naming those with spines F. fülleborni it would appear desirable to subject this species also to further investigations. goddardi 38. They had been obtained by Dr Deuntzer in Bangkok f rom a 13 year old boy who had had a typhoid fever-like illness and had expelled flukes after the administration of calomel. to indicate the similarity of this worm to F. rathouisi and F. although some authors have labelled it as F. Included in this batch of worms were fiv e helminths that had minor morphological differences: Ward named these F. 15 Meanwhile. 20. Leiper later showed that it was merely F. rathouisi and F. He studied 433 specimens then cut histological sections from 17 worms that conformed to the description of F. crassum of Busk24. Odhner named the worm Fasciolopsis buski. 1890 and Jan. . considering them to be a new species. Leuckart was sceptical and considered that it was probably identical with the D. 1891. At the outset.Fasciolopsiasis 129 Chinese woman at the Catholic Mission in Zi-kawei. it has generally retained this designation since that time. Brown in 1917 examined 118 specimens preserved i n alcohol that had been collected in Shaohsing. On account of the close similarity of F. Heanley thought tha t this was an undescribed species and it be came known as Kwan's fluke 16. This name is derived from a combination of th e Latin "fasciola" meaning "fillet" and the Greek (OPSIS) "meaning resemblance". China. buski. buskii. Since the woman had a chronic liver complaint. Germany. He finally succeeded in cultivating what he considered to be two species of snail. was the background when Koa n Nakagawa in Formosa (Taiwan) in 1915 turned his attention from the study of the life cycle of Paragonimus westermani to investigate that of F. it gave credence to the idea that fasciolopsiasis was trans mitted likewise. mantle etc. for when he placed them with F. especially into the mantle and walls of the ali- . hepatica 19. therefore. He surmised that the usual host was probably som e species of lower animal living in the tropics and that humans were likely t o acquire the infection in a fashion similar to the way in which they becam e infected with F. He noted that when eggs were deposited in water during the warmer months. The only other observation of significance that wa s made during the nineteenth century was the discovery of the operculum of the F. foot. buski. Although Cobbold had desc ribed the appearance and dimensions of these ova in 1875 11. the snails: were soon found covered by swarming miracidia which tried to bore into the head. grew and migrated. North Borneo in 1891 1. he observed that the miracidia transformed int o sporocysts. buski. buski in 1857. When this was confirmed by Thomas and Leuckart in 1882 (see chapter 4). Realizing that he had to have snails that were free of an y naturally-acquired infection (there being at least 17 different forms of cercariae present on Taiwan). He pursued his experiments over five years. Human infections with the parasite were almost unknown on that island. Plan-orbis coenosus and Segmentina largillierta (now both known as Segmentina hemisphaerula ). he apparently failed to see the operculum. buski egg.130 A History of Human Helminthology ELUCIDATION OF THE MODE OF TRANSMISSION: DISCOVERY OF THE LARVAL STAGES AND SNAIL INTERMEDIATE HOSTS When he named the parasite F. they developed over the nex t two to three weeks. Lankester speculated about the life cycle of this worm. These snails proved susceptible to infection. Lankester's suppositions were substantiated further when i t was discovered that pigs in certain endemic areas were infected not infre quently with F. although speculation that snails wer e involved was rife. but fasciolopsiasis was ver y common in pigs. tentacles. This wa s eventually discovered by an anonymous commentator who examined a specimen submitted to the British Medical Journal by JH Walker in Sandakar . buski miracidia in an aquarium in April 1920. They left their ciliated coats as they penetrated into the snail. The means by which the latter worm was transmitted was not known at that time. finally publishing his results in 1921 28 and again with more details in the following year 29. This.28 In the tissues of the snails. so he obtained his specimens from that source. then hatched miracidia which swam about freely in th e water. He incubated these miracidia with a number of species of snail s collected from local ponds and brooks but obtained either negative o r confusing results. he tried to raise s nails artificially from eggs in aquaria. eggs were not seen at any time. He then ingested thre e more flukes. he repeated the experiment with a young pig and returned similar results. The only means of being infected is to eat raw water plants. He reported the results of some of his invest igations in a number of journals over several years.Fasciolopsiasis 131 mentary canal. then three days later he gave it another 50 encysted cercariae. he infected a young dog with 40 cysts. Nakagawa had thus completed the life cycle and conclude d that: the mode of infection with F. rediae could be seen in th e sporocysts. in Formosa28 Nakagawa then attempted to infect experimental animals with these cysts. Fasciolopsiasis was a common and serious problem in the are a around Shaohsing. Nakagawa thus: concluded that the intermediate hosts of Fasciolopsis buski are Planorbis coenosus Benson and Segmentina largillierta Dkr. the cercariae were identical in appearance to those he had seen in 1918 in naturally infected snails collected from a small pond near Shinchiku where fasciolopsiasis in pigs was ver y common. they soon attached themselves to grass and encysted. buski derived from human sources. Before the life cycle of F. On the first occasion that he swallowe d living adult worms. buski is very simple. Thus. an American missionary at Shaohsing Christian Hospital i n Chekiang Province. definitely F. occurring frequently in humans but almost never in pigs. one of which lodged in t he intestines with the result that ova were discovered in the stools 28 hours later. then brought all th e available information together in a monograph of nearly 100 pages published in 19255. buski. then disappeared within eight days. in some instances. On 19 June 1920. which carry the encysted cercariae. Thereupon. 13-15 mm in length. When he swallowed eggs in gelatine capsules. young cercariae could be discerned within th e rediae. He then noticed that after the cercariae were liberated from the snail 38 days or so after infection. in thi s animal. they did not seem to be damaged in the process. The animal was killed on 16 July 1920 and 59 young distomes 2-3 mm long were found squirming around in th e duodenum and jejunum.29 The next person to apply his mind to the problem of fasciolopsiasis wa s Claude Barlow. Furthermore. Fertile eggs continued to be excreted by this single fluke until it was expelled by an anthelmintic one year later 2. buski was understood. By the seventh day of infection. daughter rediae (second generatio n rediae) developed within parent redi ae. and by 35 days. Barlow swallowed egg s (late 1918) and living adult flukes (early 1920) in order to establish the time required for stools to become free of ova after treatment and to determin e whether infection could be acquired by ingesting adult worms. Barlow's observ ations were made on F. Moreover. A third experiment was then undertaken with another pig being infected on June 1920 then killed 90 days later. they appeared in the faeces on either the same day or on the following day. the opposite situation to that pertaining in Taiwan. China. were found in the small intestine. 23 worms. . or to drink the water containing them. These findings were then reported in greater detail in th e following year when he also recorded the results of his next experiment . he observed the transformation of miracidia i nto sporocysts and the growth of rediae within them. On 23 February 1923. buski cysts. he ingested another 35 cysts obtained from aquarium-reare d snails. this intrepid investigator was ready to enter the n ext phase of his investigation. he indicated that no cases of infection in pigs had been discovered. he continued to see rediae being released for as long as 254 days after infection of the snail.132 A History of Human Helminthology In 1922. ova appeared in his faeces. Barlow developed the procedu res necessary for establishing the life cycle of the parasite in the laboratory. Planorbis schmakeri (now known as Hippeutis cantori) and Segmentina nitidellus (= S. Like Nakagawa. Furthermore. Thirty one days after the initial infection. He found that cercariae formed within daughter rediae began to emerge between 25 and 30 days after infection of the snail. hemisphaerula). even in the areas of greatest infection of humans around Shaohsing. buski in his stools 4. On 27 November 1922. indicating that it began within a few min utes of the cercariae coming in contact with plants. buski were also applicable to humans infected with cercariae emanating from human sources. buski. buski miracidia hatched from eggs in human faeces. with as many as 40 cysts being found on a single nut. Now that he had a sure and defined source of F. His graphic account of the clinical manifestations induced by infection will be recounted shortly. but that instead of leaving the host immediately through the mantle or pulmonary orifice. he passed a total of 124 ad ult F. He found that two species of aquati c snails that were commonly associated with the water caltrop. were susceptible to infection. beginning eight days after infection. . having first ascertained that his stools were free of eggs. Initially. following the administration of an anthelmintic (carbo n tetrachloride). following publication by Nakagawa of the details of the life cycle of F. thus suggesting that there may be differences be tween the porcine and human forms of the parasite3. In fact. then noted the escape of rediae from ruptured sporocysts . The red water caltrop wa s particularly incriminated. He descri bed the process of encystation carefully. Barlow reported in a preliminary note that human infection wa s acquired by eating water chestnut ( Eliocharis tuberosa) and water caltrop (Trapa natans) on which the cercariae encysted. He reared the snails in th e laboratory and followed the course of infection when they were exposed to F. and thought tha t this probably indicated multiple generations of rediae. Secondary objectives were to characterize the species of snail susceptible to the loca l strain of the parasite and to discern the symptoms induced by infection. Barlow swallowed 98 cysts collected from water caltrop in the fields nearby. Th e following day. and was completed within one to three hours. they usually remained in the liver or in th e lymph space around the heart for from a few hours to a couple of days while completing their maturation. Barlow had determined to confirm that Nakagawa's observations on the infection of pigs and dogs exposed to pig-derived F. It was of daily occurrence and came on only in the early morning. and it is difficult to disentangle the role of F. That fever was not a feature of fasciolopsiasis was recognized in 1919 b y Goddard who described three phases in the clinical picture 15. for when discussing th e condition several years later. then progressing t o involve the whole body. This symptom was the major complaint of the missionary and his wife who were treated by Spencer Cobbold on their return from China. to speculation that the febrile state was a consequence of the fluke infection. a few flukes generally caused no inconvenience except for a mild asthenia. buski and diarrhoea was moote d early. buski 5. he had a remarkably naive and immature view of the symptomatology of this infection. they must be viewed with some circumspection since t he possible causes of diarrhoea for someone living in China at that time were legion. 5 At the same time. and Cobbold was left in no doubt as to there being a causal relationshi p between the two events. Two weeks later. The clinical features of fasciolopsiasis were placed on a more defined basis when Barlow infected himself with F. he commented that: Savages of the untutored races in the matter of symptoms. he began to develop increasing hunger and epigastric pain before meals. there being mucus but . he became troubled with diarrhoea. he started having symptoms even more reminiscent of duodenal ulceration: hypogastric pain became severe and lasted from four o'clock in the morning till food was taken. 12 Several of the first reported patients had a typhoid fever-like illness an d passage of the worms was associated with resolution of the complaint. suffer much less from the presence of intestinal worms than their civilised fellow-men do. The final phase was the period in which severe anaemi a was complicated by the appearance of massive oedema beginning in the abdomen and genitals. the study was uncontrolled.Fasciolopsiasis 133 RECOGNITION OF THE CLINICAL FEATURES AND VIEWS O N PATHOGENESIS An association between infection with F. Nevertheless. however. The period of diarrhoea was characterized by persistent passage of frequent. buski in engendering these features from the multitude of other infectious agents and non-infectious conditions which might produce similar effects in people with coinciden t F. but it was realized subsequently that the worms wer e merely co-existent and that the unfav ourable environment induced by the fever caused them to be expelled. offensive stools containing poorly-digested food material. Nearly ten weeks after infection. naturally enough. plus a profound anaemia. the diarrhoea resolved when the flukes were expelled . buski infections. During the period of latency. Thi s led. It was griping in nature and continued for half an hour after eating then subsided entirely. Barlow noticed no particular ill-effects when the infection became patent 31 days after he had swallowe d 132 cysts. Whethe r coincidentally or not. although even here. Although this description was based upon observation of many patients. 5 ml) of carbon tetrachloride in water at 7. None were loose in the bowel.m.5 These four stools contained a further 73 flukes. buski resulted in diarrhoea. He believed that these complications were most likely to arise if the patient was small and undernourished and at the same time wa s infected heavily. buski infection was the cause of the patients' trouble. The pain was confined to the hypogastrium and seemed to be caused by an increased peristalsis and a large quantity of gas. Barlow went on t o note that diarrhoea was absent in many patients with this infection. that infectio n with F. there was a marked aversion to food..15. At midday. this feeling subsided and a comfortable night was passed..(the drug) made me feel decidedly ill.13 . A number of early authors subscribed to the view that many of the symptoms and signs o f fasciolopsiasis were due to toxins produced by the flukes 5. There was little doubt. with from four to six movements daily. The pain was so intense that lying on the abdomen was the only way to get relief. and the absence of anaemia or oedem a could be explained easily enough on the basis that the infection was of either insufficient intensity or duration to induce these effects.within twenty four hours of admission for bowel troubles. in which the typical ova were demonstrated before death. with six movements during the 24 hours.They may remain attached to the mucosa till little reddened spots appear. Cole wrote that: I had one death. he implied that anaemia wa s merely a dilutional consequence of the fluid overload causing ascites an d peripheral oedema. Thus. accompanied with severe griping pain which was irregularly intermittent all day long... nausea and tinnitus. Indeed. many authors 13. he passed a large. During the periods of diarrhoea. loose stool containing 20 flukes and one ascarid: There was a constant and nauseating eructation of carbon tetrachloride gas and the whole treatment was accompanied by weakness. and re marked that anaemia was infrequent.134 A History of Human Helminthology no blood in his stools.13. He described such a patient: she was a nine year old gir l suffering from oedema who passed 3. On 13 February 1923.721 flukes after treatment wit h betanaphthol 5. dizziness. 77 days after infection: a severe diarrhoea. This was based upon the often false assumption that F.. 5 These problems then subsided somewhat and on 27 February he treated himself with 90 minims (7.. then another 33 worms were passed on the following day. 5 It was not surprising that such lesions should induce pain with many of th e features reminiscent of those seen in duodenal ulceration. If oedema and these other effects are indeed a feature of severe fasciolopsiasis and are due to the liberation of toxins by flukes in the bowel. Initially.15 took an alarmist view of fasciolopsiasi s considering that the infection "may be fatal unless the parasites are expelled by art or accident" 13. but after four stools. Barlow also described the location of flukes in the small intestine: (They) were all in the duodenum and all fastened to the mucous membrane by their suckers or were buried in mucous secretion. the toxin or toxins whic h produce them have not yet been identified nor have the mechanisms by which they produce these ill-effects been clarified. therefore...30 a.. began and lasted till the 20th of February. buski eggs in the faeces was JH Walker in British North Borneo in 1891. as the eggs of F. He had more luck with a second patient in whose faeces he foun d similar eggs.. buski was not responsible for overt clinical disease unless the parasite was present in massive numbers 32. the clinical features in 28 infected persons were compared with those in an equal number of uninfe cted control subjects living in the same endemic area of Thailand.Fasciolopsiasis 135 Nevertheless. Even had he done so. th e patient pronounced himself cured but failed to bring the parasites to th e hospital. 5 although he also claimed that "fluke-harboring individuals are easil y recognized on the streets after one has seen many cases clinically" 5. particularly in the heavily endemic area around Shaohsing in China. No significant differences in symptomatology . Nevertheless.. growth and development. Microscopical examination of the faeces then became standard practice . Stoll and his colleagues took this diagnostic procedure one step further and . and it was concluded that F. however. The first person to find F. it became clear gradually that the severity of infection wa s dependent upon the worm burden and might be grave only in those with extremely heavy infections if left untreated. buski were not described at that time. More recently.very numerous eggs of a kind I could not find described in any books at my disposal. 37 He then went on to describe the eggs and provided a figure illustrating one . In a 22 year old Chinese male with beriberi: microscopic examination of the faeces showed that they contained. anthelmintic therapy resulted in the recovery of an adult fluk e which he identified as Distoma crassum. while it is almost impossible to overlook ova in the stool when but one fluke is harboured because of a large number of ova discharged by one adult. wit h Barlow remarking that: in diagnosing fasciolopsiasis there are only two pathognomonic signs. Only in cases of massive infestation does the latter occur. haematological parameters or screening tests fo r malabsorption were found between the two groups. DEVELOPMENT OF DIAGNOSTIC METHODS It is perhaps remarkable that wh en Cobbold in 1875 found that his patient had fasciolopsiasis.. Walker attempted to ascertain the the adult worm producing these eggs b y treating the patient with a combination of anthelmintics and purgatives. even though such a technique had been described nearly 20 year s earlier. this diagnosis was made only because adult flukes wer e passed in the stools. observation of their presence would have alerted him to the existence of some intestinal worm in the gastrointestinal tract. Apparently he was not in the habit of examining microscopically the faeces of patients whom he suspected of having an helmint h infection. the finding of ova in stool and the vomiting of live flukes. he would not have arrived at the correct diagnosis. Between 40 and 50% of the hospital patients were infected. The discovery by Nakagawa of the snail intermed iate host of F. In 1937. Turpentine and carbon tetrachloride enjoyed transient popularity but they were soon abdandoned because of severe damage to the kidneys and liver. It has a broad.000 ova per day36. They treated 129 children with this drug and found that when the faeces were re-examined two to three weeks later.000 and 48. Tetrachlorethylene also enjoyed som e transient favour. but identified two major types of plants . In more recent times dichlorophen has been shown to be relatively effective 17. they treated 85 children with small doses and all of them wer e cured9. This was extended by Barlow who not onl y confirmed the life cycle of F. buski 37. fasciolopsiasis was found to be common in various regions of South and Eastern Asia. . Bunnag and his colleagues reported that praziquantel (see chapter 3) wa s effective. In 1983.15. UNDERSTANDING THE EPIDEMIOLOGY Despite the initial paucity of reports. as the final vehicle of infection to humans. One of the most heavily infected areas was the Shaohsing region of China. McCoy and Chu introduced therapy wit h hexylresorcinol. all of the inhabitants carried the fluke. They further demonstrated that each fluke produce d between 15. although it had to be given i n repeated small doses in order to reduce the frequency and severity of depression as a side-effect 6. while in some villages. A traditional Chinese remedy which had some measure of success was areca nu t combined with cathartics. He expounded the reasons why caltrop was so important in transmission: The caltrop is a most acceptable feeding ground for the snails. soft. This anthelmintic is likely to become the drug of choice for th e treatment of fasciolopsiasis. buski and his realization that infection was acquired by ingesting metacercariae encysted on water plants immediately shed light on the epidemiology of fasciolopsiasis .136 A History of Human Helminthology showed that quantification of the number of eggs in the stools was a valuable index of the number of adult worms with which a person was infected. Experience in China then showed tha t betanaphthol was the best available drug. respectively 6. buski by deliberate infection of a human. THE SEARCH FOR EFFECTIVE TREATMENT Walker in 1891 showed that a combination of thymol and santonin togethe r with calomel and senna purgatives was effective against F. that 54% of them were cured and that most of the remainder had a reduction of 80% or more in egg counts26. water chestnut and water caltrop. where Barlow believed that i t occasioned greater economic loss than did hookworm and schistosom e infections put together 5.27. leaves and nuts.5 Water caltrop and water chestnut were grown in shallow ponds and infection was enhanced by fertilizing with human night soil. although there is a root which is sent down to the bottom. before swallowing the raw food. petioles. The most common way in which humans acquired infection was by peeling off the outer covering of each nut with teeth. These snails were somewhat difficult to identify and there was considerable confusion initially. For this reason. even though the depth may be 12 or 15 feet. while the consumption of uncooked freshwater fish and .Fasciolopsiasis 137 spongy leaf on a fibrous. even though they were located near ponds containing many infecte d snails. Salvinia natans and Lemna polyrhiza 18. Nakagawa noted that porcine fasciolopsiasis was common in Taiwan. vegetables which were grown on dry soil were not inf ected. Nakagawa was quick to list various measures designed to reduce the transmission of infection. buski. nitidellus) and Hippeutis cantori (= Planorbis schmakeri of Barlow) were found to be the major molluscan hosts in eastern Asia. These plants are usually alive with little snails. Likewise. H e indicated that the eating of raw water pl ants and the drinking of unboiled water should be prohibited. largillierta and his Planorbis coenosus and synonymous with Barlow's S. THE EVOLUTION OF PREVENTIVE AND CONTROL MEASURES Once he had discovered the life cycle of F. water bamboo. cysts were described on the roots and leaves of lotus. Subsequent experience in other endemic regions indicated that F. buski cercariae were not fastidious but could live on almost any kind of water plant growing in stagnant water near infected snails. Thus. trochoideus was identified as the most important vector in northeaster n India. The air cells keep the plant supported on the water. Barlow then went on to examine the durability of cysts and found that they were not very resistant to drying. It is not unusual to find more than 20 on a single nut. whil e S. the important snail intermediate hosts in various regions wer e characterized. and the rootlets get their food largely from the water. although the parasite appeared to be somewhat smaller 5. feeding on the tender skin on the stems. The interaction between the pig and human cycles also caused some con sternation at first. Barlow showed that pigs could be infected with cerca riae derived from human sources. cellular petiole and the root-stalk is spindle-shaped and cellular. Segmentina hemisphaerula (identical with Nakagawa's S. This obliterates distance for the emerging cercariae and brings encystment where it is more efficacious and dangerous. being unable to withstand one day in the hot sun. Surveys of these plant s showed that there was an average of 17 cysts for every caltrop nut. whereas human infe ction was prevalent around Shaohsing. On the suppos ed rarity. 1860 11. declaring that: with things as they are. A study of two species from Chekian g Province. The treatment of fasciolopsiasis. BARLOW CH. they were difficult to p ut into practice. ANONYMOUS. American Journal of Hygiene Monograph Series. structure. Southeast Asian Journal of Tropical Medicine an d Public Health 14: 216-219. living conditions regulated. With laws effective. 1917 8. China Medical Journal 36: 546. as should the washing of table utensils in ditches and rivers. Diseases of the liver. Field trial on the treatment o f fasciolopsiasis with praziquantel. The life cycle of the human intestinal fluke Fasciolopsis busk i (Lankester). Experimental ingestion of the ova of Fasciolopsis buski : also the ingestion of adult Fasciolopsis buski for the purpose of artificial infestation. J&A Churchill. Furthermore. pp 99. China Medica l Journal 37: 453-472. fasciolopsiasis is still a problem. pp 508. and in many regions . London. 1852 9. No 4. John Churchill. 1875 12. 1925 6. A rare parasite. pp 486. COBBOLD TS. h e recommended that faeces contaminated with eggs should be dis -infected .5 But he was not sanguine about the likely outcome.138 A History of Human Helminthology molluscs which sometimes contain encysted cercariae should be avoided. BROWN NW. Journal of Parasitology 8: 40-44. London. The Fasciolopsinae of China. Transactions of the Royal Society of Tropical Medicine and Hygiene 14: 93-96. 1983 10. and 50 years or more to stamp it out completely. Journal of the Linnean Society. COBBOLD TS. Synopsis of the Distomidae. looking with optimism on the problem of control. Life cycle of Fasciolopsis buski (human) in China. even this forecast was too optimistic. 1922 4. BUDD G. 1879 13. BARLOW CH. Barlow noted that: the possibility of control is fairly simple and easily accomplished. COBBOLD TS. This is a desideratum hardly to be contemplated. and ought to be effective. and that the intermediate hosts should be destroyed 28. While these measures were simply stated. 1921 . BUNNAG D. 5 Unfortunately. infected domestic waste should be disposed of. second edition. BARLOW CH. 1923 5. one may predict that it will take from 10 to 20 years to reduce the disease to the point at which it will cease to be a menace. and customs subordinated. nomenclature. Johns Hopkins Hospital Bulletin 28: 322-329. 1891 2. easy to recommend. Five cases of Fasciolopsis infection. 1921 3. Parasites: a treatise on the entozoa of man and animals including some accounts of the ectozoa. COLE AF. BARLOW CH. RADOMYOS P. China Medical Journal 41: 253-265 . REFERENCES 1. with remarks. London. HARINASUTA T. 1927 7. affinities and source of the large human fluke (Distoma crassum Busk). Journal of the Linnean Society 12 : 285-296. British Medical Journal ii: 1224-1225. Life cycle of Fasciolopsis buski : discovery of the means of infestation of human beings. Zoological Division 5: 1-56. unless Chinese officialdom and the common people cooperate in a common plan with the control-man to eradicate it. In echoing these measures. BARLOW CH. the disease could be blotted out in one season. NAKAGAWA K. Archives de Zoologie Expérimentale et Générale 5: 203-211. Fasciolopsis buski as a parasite of man in Hongkong. Weitere Beiträge zur Kenntnis der Trematoden-Fauna Aegyptens zugleic h Versuch einer naturlichen Gliederund des Genus Distomum Retzius. 1922 30. F. PLAUT AG. Proceedings of the Academy of Natural Sciences . Ein Hand. C F Winter'sch e Verlangshandlung. Paris. Fasciolopsis füllebor ni n. LEIPER RT. Bangladesh Medical Journal 7: 45. sp. Fasciolopsis buski (Lank. Bulletins de la Société de Pathologie Exotique et de ses Filiales 4: 693-699. MUTTALIB MA. LEIDY J. Note sur une nouvelle espèce de Distome parasite de l'homme le Distomum rathouisi. pp 897. Deux nouvelles plantes pouvant transmettre le Fasciolopsis buski . Centralblatt für Bakteriologie . GODDARD FW. 1978 28. LEUCKART R. Parasitenkunde und Infektionskrankheiten. The treatment o f fasciolopsiasis with niclosamide and dichlorophen. RAILLIET A. In. ODHNER T. Journal o f Parasitology 8: 161-165. LEUCKART R. Die menschlichen Parasiten und die von ihnen herrührende n Krankheiten. 1980 18. A manual of their natural history. On the life cycle of Fasciolopsis buski . pp 776.) ein bisher wenig bekannter Parasit des Menschen in Ostasien. Revue générale. POIRIER J. NAKAGAWA K. McCOY OR. Ein Hand. 1937 27. pp 838. The development of Fasciolopsis buski (Lankester). LOOSS A. Appendix B. HEANLEY CM.) (= Distomum crassum Cobb. Chinese Medical Journal 51: 937-944. 1937 19. Was is Distomum rathouisi ? Archives de Parasitologie 12: 573-581. On Kwan's fluke and the presence of spines in Fasciolopsis.Fasciolopsiasis 139 14. diagnosis and treatment. Proceedings of the Academy of Natural Sciences . China . RAHMAN KM. 1908 17. LANKESTER ER. pp 234-236. 1911 35. 1857 20. 1863 24. Abteilung originale 50: 451-461. Journal of Tropical Medicine and Hygiene 14: 119-120. MANNING GS. Volume 1. MUTTALIB MA. Zoologische Jahrbücher. a parasite of man as seen in Shaohsing. London. Abtheilung für Systema 12: 521-784. LEIDY J. Journal of Tropica l Medicine and Hygiene 11: 122-123. Journal of Tropical Medicine an d Hygiene 83: 71-74. CHU TC. its usual host probably the pig. 1911 23. volume 1. translated by E Lankester. C F Winter'sch e Verlagshandlung. pp 452. Helminthes du porc receuillis par M. Küchenmeister's "On animal and vegetabl e parasites of the human body. HENRY R. Parasitenkunde und Infektionskrankheiten. de l'homme et de s animaux domestique. KUANG WU. ODHNER T. STOLL NR.und Lehrbuch für Naturforscher und Aertze. 1886-1901 25. Transactions of the Royal Society of Tropical Medicine and Hygiene 63: 470-478. Dichlorophen in the treatment of Fasciolopsis buski . DAVAINE C. 1873 21. A large fluke of man probably not hitherto described. Kitasato Archives of Experimental Medicine 4: 159-167. Centralblatt für Bakteriologie. Die Parasiten des Menschen und die von ihnen herrührende n Krankheiten. volume 2. 1899 26. CORT WW. 1909 32. Annales de Parasitologie Humaine et Comparée 15: 458-464. 1919 16. Egg-worm correlations in cases of Fasciolopsis . Philadelphia. Animal parasites belonging to the group entozoa". Fasciolopsis buski . 1902 31. 1921 29. Leipzig. IDRIS M. KAMPANART-SANYAKORN C. Lankester. 1891 22. 1860 15. 1887 34. Philadelphia 25: 364. On Distoma hepaticum . 1969 33. J-B Baillière et fils. RODENWALDT E. AZAD KHAN AK. KWEI WS. Notice of entozoa.und Lehrbuch für Naturforscher und Aertze. Bauche en Annam . The Sydenham Society. A clinical study o f Fasciolopsis buski in Thailand. Fasciolopsis buski infection among school children in Shaohsing and treatment with hexylresorcinol. Leipzig. Journal of Parasitology 5: 141-163. 1909 36. Traité des entozoaires et des maladies vermineuses. Abteilung originale 31: 573-581. observed development through to the cercarial stage in snails. British Medical Journal ii: 1205.140 A History of Human Helminthology buski with additional data on the distribution of this parasite in China. Anchylostoma duodenale and other parasites. rathouisi and related species in China. F. 1891 38. China Medical Journal 24: 1-10. 1909 Table 5. Journal o f Parasitology 13: 166-172. WARD HB. Fasciolopsis buskii. 1927 37. Landmarks in fasciolopsiasis ___________________________________________________________________ 1843 1857 1891 1918 1920 George Busk discovered the adult worm Lankester named the worm Distoma Buskii Walker diagnosed fasciolopsiasis by finding eggs in faeces Barlow experimentally swallowed eggs Nakagawa hatched miracidia from pig-derived eggs. Two cases of beri-beri asso ciated with Distomum crassum . WALKER JH. then recovered adult worms from experimentally infected pigs 1920 Barlow swallowed adult worms and developed a persistent infection 1922 Barlow swallowed cysts and developed a patent infection 1937 McCoy and Chu introduced treatment with hexylresorcinol 1983 Bunnag and colleagues demonstrated the efficacy of praziquantel __________________________________________________________________ .1. noted encystation on plants. the bile ducts (were) particularly distinct from their large size. swim about in the water until they encounter certain freshwater fish (at least 80 species. and on more carefu l 141 .Chapter 6 Clonorchis sinensis and CLONORCHIASIS SYNOPSIS Common name: Chinese liver fluke Major synonyms: Distoma sinense. 10-22 mm long and 3. spathulatum. transparent and spatulate hermaphroditic worms. a 20 year old Chinese carpenter was admitted in a moribund condition to the Medical C ollege Hospital in Calcutta. A post mortem examination was performed later that morning by James McConnell. the metacercariae excyst in the duodenum. and distension with thick yellow bile. D. it was noticed that small. pain and tenderness in the right hypochondrium. jaundice. The miracidia develop into sporocysts then in turn become rediae which produce cercariae. When raw. He had been febrile for two weeks and died several hours after admission. vermicular-looking bodies escaped onto the table. Melanoides. India. They produce eggs which are passed in the faeces.. professor of pathology and resident physician. who noted that the patient was jaundiced and that: the liver was dark. Parafossarulus. Bulimus. dogs. lose their tails.. penetrate under the scales. dark . attach to the surface. The cercariae emerge from the snail.. and develop over 3-4 weeks at summer temperatures. hepatomegaly in heavy infections Diagnosis: demonstration of eggs in the faeces or duodenal aspirate of patients with patent infections Treatment: praziquantel DISCOVERY OF THE ADULT WORM On 8 September 1874. infected fish is eaten by humans. cats Major clinical features: fever. D. Semisulcospira). encyst in the skin or flesh. mostly of the family Cyprinidae are susceptible). swollen and tense. endemicum Distribution: eastern Asia Life cycle: The flat. enter the common bile duct through the ampulla of Vater and ascend to the small biliary passages where they mature in one month Definitive hosts: humans.. The miracidium hatches only after ingestion of the egg by a suitable species of operculate snail (Alocima.5 mm wide live in the biliary passages attached to themucosa. O n incising the liver in different directions. Baelz recognized two forms of the fluke: he regarded the smaller form as being pathogenic and named it Distoma hepatis endemicum sive perniciosum and the larger type as being nonpathogenic. however. In 1878. which were nearl y one inch in length. This led McConnell to the conviction that th e flukes that he had found in the liver "not only differ from the ordinary live r fluke (Dist. McConnell again found the parasites in a Chinese cook from Hong Kong 46. he ascribed the pa ralysis to these worms 47. In 1895. Leuckart. sinense in it6. the nam e being derived from the Greek words (CHLON) and (ORCHIS) meaning "branch" and "testis".. Ijima. and that the "cholaemic condition" induced by obstruction of th e biliary channels was the immediate cause of death. in his textbook . Raphael Blanchard erecte d the genus Opisthorchis and placed D.No distomata were found in the gall-bladder. labelled the parasite Distoma spathulatum 43. calling it Distoma hepatis endemicum sive innocuum 3. . hepatica (see chapter 5). then compared them with the two flukes well-known i n Europe. In the following year. Distoma hepaticum (Fasciola hepatica) and Distoma lanceolatum (Dicrocoelium dendriticum).. Arthur Looss created the genus Clonorchis for this oriental liver fluke with branched instead of lobed testes. all were dead. and ought to have som e distinctive name by which it may be recognised amongst th e trematodes. I propose to call it Distoma sinense. which. nor were any ova discovered on microscopical examination of the bile and lining membrane of this sac . as well as discussing them in relation to Fasciolopsis buski found in China by Kerr and wrongly identified by Leidy a s F. Ishizaka discovered the infection in a farmer in Okayam a Prefecture in Japan31..11 This name was presumably intended to indicate its discovery in the body of a Chinese person. on being dissected. believed them to be identical and shortened the name of the parasite to Distoma endemicum 30. His paper was published in The Lancet on 21 August 1875 then four weeks late r Spencer Cobbold wrote to the editor of that journal remarking that: without doubt the species is new to science. The parasites were encountered again in 1877 by William McGregor i n Port Louis. others coiled up and either solitary or in groups of twos or threes within the biliary ducts. however. Naturall y enough. Numerous ova and shreds of epithelium were found in the biliary canals. Eight Chinese persons were suffering from a paralytic illness. however. 45 McConnell concluded that the flukes in the bile ducts caused degeneration of the liver. and he found the flukes in the three patients who died. hepaticum) but constitute an entirely new species" 45. He recognized two species .142 A History of Human Helminthology examination these were clearly seen to protrude from the bile ducts. were found more or less obstructed by and containing them in large numbers. some lying fr ee. but quite wrongly. In 1907. Mauritius. then Erwin Baelz recovered the worms during th e autopsy of a patient in Tokyo University Hospital in 1883. respectively 44. He then went on to describe the external and internal morphology of the flukes. In the same year. Corbicula. moreover. describe the appearance of miracidia forced out o f their shells by tapping coverglasses sharply. a smaller worm which was thought to be found mainly in Japan and Indochina. Ijima remarked "I have no expectation of bringing them soon to a close" 30. ELUCIDATION OF THE MODE OF TRANSMISSION: DISCOVERY OF THE LARVAL STAGES AND INTERMEDIATE HOSTS When McConnell described the adult fluke in 1875. redia or cercaria in any one of thes e snails. He then canvassed four possible ways in which humans migh t acquire infection. however. Melania. Using those flukes whose life cycle had already been worked out. and he was unable to hatch them artificial ly. &c. ingestion of infecte d . th e "bêche-de-mer" 47 and was reinforced when McConnell found the parasite in yet another Chinese person 46. This difficulty hindered experimental attempts to investigate the life cycle in the same way that Thomas and Leuckart had recently done for F.. sinensis 36.Clonorchiasis 143 Clonorchis sinensis. These embryos were non-motile. considering that the size of the adult worm depended upon the nature and size of the host and upon the in tensity of infection. Cyclas. and suggested that the vehicle might be a species of snail. His epidemiological observations allowed him to speculate on the nature of the life cycle of the parasite. He dissected a large number of aquatic snails including species of Anodonta. and believing that there were no significant differences in the shape of the eggs. In 1885.. despite keeping them for over five months and placing them in an incubator. he surmised tha t they might have become infected by ingestion of certain contaminated fishes or vegetables since: Chinese. Paludina and Planorbis but failed to discern any trace of sporocyst. of all kinds of 'vegetable food'. Isao Ijima began to investigate the life cycle of C. Kobayashi (1912) . Lymnea. he also described an d illustrated the eggs that he found in the bile. Since these people were Chinese. particularly Fasciola hepatica (see chapter 4) as an analogy.are well known to be 'filthy feeders' delighting in putrid messes of half-raw fish. a larger form that he believed was found more commonly in China. H e recalled seeing several patients with clinically enlarged livers who may have been similarly infected. fish or fowl'.. sinensis 30. they partake. including drinking of ditch water.38. endemicus. C. In noting that he was carrying out suc h experiments. he fixed his attention o n molluscs. and C. concluded that there was only one species. 45 This idea received further support when M cGregor found the infection in more Chinese. The sources from whence th e larvae of such parasites may be deri ved are therefore not far to be sought. they are bound by no caste prejudices (as the natives of India are) to abstain from any kind of 'flesh. however. hepatica. In addition. Looss believed that the shapes of the eggs differed between the two forms of the worm. He did. Th e freshwater snail (Paludina sinensis) is also eaten more or less cooked. he fed them to kittens. sometimes raw. but noted that one particular kind of immature. boi led rice and tinned milk. He examined a variety of molluscs. he used these animals for experimental studies.. These findings were first reported by Kobayashi in the form of a short note in Japanese in 1911 35. endemicus) in the bile duct. In 1913. also claimed to have determined the life cycle of C. fishes and aquatic arthropods while looking fo r trematode larvae. pancreas and duodenum. Similarly. gall bladder. all were found to be infected wit h C.144 A History of Human Helminthology snails. These frustrations led Heanley to adopt the view that: the easiest way of finding out something of the life history of O. China. They either died or were killed at varying intervals. all attempts by Heanley (1908) to hatch eggs failed. where he was working.There is a dish frequently eaten which contains uncooked vegetables and fish. In view of the possibility that these larvae might parasitize humans or some other mammalian host.. encysted fluke wa s common in certain freshwater fish that came from the same regions wher e human clonorchiasis was freque nt. sinensis will be to feed animals with food eaten raw by Cantonese. In the first experiment. Saito (1898) developed a mechanical method for expressing the m iracidia and claimed to observe larvae exit from ova spontaneously 63. while the other . Kobayashi then fed them exclusively on a diet of boiled rice and disinfected milk. hepatic ducts. consumption of vegetables contaminated with cysts. however. Nine kittens and two cats were fed on the fishes Pseudorasbora parva and Leucogobia guntheri. Houghton noticed the practically constant presence of a larval trematode free in the intestine of a species of fish of the genus Notropis. Since cats were known to be often infected naturally. He even caused many molluscs to ingest eggs but they were passed in the excreta unhatched. but this was not the general experience and did not provide sufficient numbers of miracidia for experimental purposes. one with raw fish. then appeared in English the following year 37. sinensis 25. sinensis (Kobayashi called the worm C. two suckling kittens were fed. and by eatin g undercooked second intermediate hosts such as shrimps and fishes" 30. while working in Korea. While making some observations in 1910 o n parasites present in foodstuffs commonly eaten in Shanghai. 20 Heanley followed his own advice and fed several dogs with various types of food but failed to achieve any positive result. a western physician. They were firs t shown to be uninfected by repeated examination of the faeces then given the flesh of fish containing these cysts. He found a number of fo rms of cercariae and encysted young flukes. DISCOVERY OF THE FISH SECOND INTERMEDIATE HOSTS Heanley's approach was adopte d with success several years later.. The inability to hatch eggs continued to be a bugbear. Houghton. by the Japanese zoologist Harujiro Kobayas hi. and I was told. In these papers. sinensis in an ingenious manner. guinea pigs and rats. Previously. Muto thought it unlikely that this species of snai l was also the primary intermediate host of C. bot h kittens died of an intercurrent illness after o ne month. he found that the animal fed with fish was infected with C. with hundreds of Clonorchis being recovered. Houghton concluded that although his data were scanty. Kobayashi thought it highly likely that a mollusc was involved and suspected Melania species as prime candidates. Kobayashi continued his studies using cats. Despite Houghton's claim that th e intestinal larvae were the only trema todes found either in the gut or in the flesh of the fish. On killing the animals two months later. The experiment was repeated and similar results were returned. so that by 1965. dogs.Clonorchiasis 145 received rice and milk only. but while pursuing this line of investigation. thus causing him to misinterpret the relationship between th e intestinal larvae and the adult worms that he reared. Japan. describing his findings in Japanese in 1912 36 and in English in a German journal published on 15 January 1915 38. the mode of infection of the fish remained unknown. He observed that cysts were abundant both in the subcutaneous tissues and in the muscles o f fish. skirted around the difficulty of obtaining miracidia and solved the riddle of the primary intermediate hosts of C. sinensis. he had been investigating parasites in s nails and had shown that the river snail. rabbits . approximately 80 such species had been identified 40. Thus. although Kobayashi had demonstrated conclusively tha t experimental animals. sinensis by ingestion of infected fish. Kobayashi and other workers found further species of freshwater fishes tha t were vectors of C. Masatomo Muto (also known as Shochi Muto) . DISCOVERY OF THE SNAIL FIRST INTERMEDIATE HOSTS The Japanese pathologist. acquire d infection with C. his findings must be viewed with some scepticism. and therefore almost certainly humans. not encysted in the flesh. Indeed. Thiara (=Melania) libertina (which Kobayashi had proposed as the likel y intermediate host of C. sinensis. Nevertheless. Leiper and Atkinson in 1914 made a similar finding in fish near Shanghai and concluded that it had nothing to do with the life cycle of Clonorchis 42. This snail harboured three species of cercariae. Later. Meanwhile. particularly in the more superficial parts. it is possible that C. sma ll cyprinidine fish. since the larvae he saw were lying free in the intestines. Koshu. On the third attempt. although only a dozen or so were important sources of human infections 78. In order to determine . he showed that another ten species of freshwater fi shes also acted as intermediate hosts. came across a new species of snail in Lake Biwa. sinensis whereas the control cat was not. nor did subsequent investigator s give any credence to his work. sinensis) was the primary intermediate host o f Metagonimus yokogawai. sinensis cysts were present conincidentally in the skin. it seemed likely that clonorchiasis was acquired by ingestion of undercooked. Japan. for when he infected a rabbit with cercaria e obtained from snails (rabbits having been shown by Kobayashi to be susceptible to infection) adult worms were not found. he fed a third dog with P. Korea. he demonstrated that fishes were a necessary stage in the development of the parasite. In his first experiment. sinensis were found at autopsy. cyst-free fish which were in turn fed t o uninfected mammalian definitive hosts. sinensis. however. parva which had been incubated with T. two of which were fed with P. Muto obtained a miracidium of C. In his more definitive paper reported later that year. In this way. The susceptibility of this latter species to infection . sinensis and infected a snail with it. China where cats but not humans were commonly infected12. Taiwan and probably in Indochina 1. and two of which were given uninfected P. He repeated this experiment with four guinea pigs.146 A History of Human Helminthology whether one of these forms was C. then large numbers of adult C. There was little doubt that these sna ils were the primary intermediate hosts of C. He summarized his finding s thus: I collected a species of snail ('mametani shi'). Furthermore. Faust and Khaw (1927) regarded Bithynia fuchsiana (= Bulimus fuchsianus) as the major vector of C. sinensis ova appeared in the dogs' faeces 18 and 20 days later. C. Abbott proposed that the Bithynia striatula of Japan and China should be incorporated into the species Parafossarulus manchouricus which is distributed widely in China. parva to small dogs and guinea pigs and confirmed th e existence in these animals of parasitism by C. I proved that the primary intermediate host of C. Finally. In 1948. sinensis in northern China and considered that Bithynia longicornis (= Alocima longicornis) was a less important potential vector 16.52 Muto's findings were first presented to the eighth meeting of the Japanes e Pathological Association in April 1918.Bulimus striatula var japonica Pilsbury. In order to substantiate this conclusion. parva to eat. Other species of molluscs were then shown to be intermediate hosts o f C. sinensis was found in the first two animal s whereas the second two remained uninfected. Melania hongkongensis was found in 1924 to be the vector around Shaohsing. Muto visited a number of endemic areas and showed that there was a strong correlatio n between the prevalence of clonorchiasis in humans and the presence of these snails. in this paper. C. he used these naturally-infected molluscs to infect experimental..and discovered three species of cercaria in the shell. Metagonimus but not Clonorchis was recovered from this animal. sinensis in various regions.. parva incubated with the snails in question. As a control. the snail was identified as Bithynia striatula var japonica 51. I fed the P.. sinensis is 'mametanishi' . sinensis. when he examined the snail three weeks later. sinensis. he fed tw o small dogs with the fish Pseudorasbora parva which had been incubated in a tank with the snails. he found a sp orocyst and wrote: "This corroborated my conviction and the results of my experiment" 52. parva with one of these species. libertina. the snail was referred to as Bulimus striatula var japonica52. After a certain period . I succeeded in infecting uninfected P. discarded their tails. Three or four weeks were required for complete development into metacercariae at temperatures occurring during summer. Galliard (1938) found that Bithynia chaperi and Melania tuberculata were the major intermediate hosts of the infection in Vietnam 18. dogs and guinea pigs . they produced rediae which in turn migrated primarily into the liver. he devised some experiments to ascertain the route by which the parasites migrated in the definitive host. and produced cercariae within them. Young flukes were found in the bile duct as early as six hours after infection . many flukes managed to escape. Discovery of the snail intermediate host permitted observation of the fate of these cercariae. the cercaria e became attached to the fish. Cats were fed with fish meat containing C. miracidia hatched within one hour then penetrated the gut wall to become sporocysts within four hours of infection. penetrated under the scales and encysted in the subcutaneous tissues or in the muscles.Clonorchiasis 147 with C. A variety of mechanical stimuli such as placement of ova in runnin g water34 were deemed to be ineffective. After escaping from the snail and having a brief free swimming existence. The sporocysts the n migrated into the lymph spaces surrounding the intestine and rectum. 38 The next person to investigat e the route of migration was Takayuki Mukoyama in Japan50. There. the cysts remained undissolved in the gastrointestinal contents for many hours after exit of the parasites. STUDIES OF THE MIGRATION AND DEVELOPMENT OF LARVAE AND THE PATHOLOGICAL RESPONSES OF THE DEFINITIV E HOST When Kobayashi discovered that the infection was acquired by ingestion of infected fish. sinensis cysts. worms were found both in the gall bladder and in the bile duct. Kobayashi interpreted these results in th e following manner: It is quite natural to infer that after they reach this part they go into th e hepatic duct and in it they cease to travel and grow. but also into other regions such as the foot and mantle. Meanwhile. Attempts continued meantime to persuade miracidia to hatch from eg g shells. then dissected at various intervals. Secondly. These authors showed that when eggs were ingested by Bithynia fushsiana. He fed encysted larvae to rabbits. sinensis was confirmed experimentally b y Hsu and Li in 1940 27. It was eventually shown by Hsu and Li in 1940 that miracidia hatch only in the alimentary canal of susceptibl e snails28. some of the cysts were found to be empty and the young flukes were creeping about with the aid of their suckers in the gut lumen. Three hours after ingestion. Kobayashi was of the opinion that the metacercariae bur st through the cysts walls by their own exertions rather than that the walls were digested by the gastric juices for two reasons. when fish flesh wa s crushed and soaked in water. Firstly. When two cats were dissected 15 and 24 hours after infection. duodenum and stomach. wherea s concomitant infections with other worms such as Ascaris.20 Heanley. however. massed in the region of the opening of the common duct. Furthermore. The only places in which worms were ever seen were the biliary system. Thus. Similarly. He was not impressed by the damage produced b y these worms. young flukes attached themselves to the duodena l mucosa. they may live there for many years. He examined 300 unselected livers at autopsy during an 18 month period and found that 109 of them were infected. Mukoyama concluded that young fluke s were unable to penetrate the intestinal mucosa but migrated directly along the bile duct. since it is possible tha t infection could have been acquired for example. Nevertheless. one person who had live d continuously in Costa Rica for 25 years retained his infection with C. when the bile ducts were ligated. liver or abdominal cavity. Finally. the worms failed to migrate to the liver and bile ducts during the three and a half weeks of observation. there are reports of Chinese emigrants continuing to pass eggs after long periods of residence in non-endemic areas. When he first found the flukes. reported the first major series of patients with clonorchiasis. with the average burden in adult persons being of the order of 40-50 worms. in fact. Although Muto found that most worms in infected dogs died during the space of two to three years 53. th e consequences of infection were of mor e concern to pathologists and clinicians. McConnell believed that they had played a major part in causing the deat h of his patient 45. and McGregor thought that the flukes produced a paralysis of reflex origin 47. the number of flukes present rangin g between one and 350. when young flukes were placed directly into the peritoneal cavity of rabbits. remarking that: . and this was echoed a number of years later by Heanley in Hong Kong when he wrote that: The literature of tropical medicine abounds with instances of commo n parasites being mistaken for causes of disease until further investigatio n has shown the parasite to be as common in the healthy population as in the sick. Since that time. sinensis ova were found in the bile of a Vietnamese who had lived in New Caledonia for 24 years7 and another Chinese patient still had clonorchiasis after living in Panama for over 40 years 9. Nevertheless. these reports must be viewed with some circumspection. McConnell had doubts abou t this. C. Similar conclusions wer e reached several years later by Faust and Khaw who observed that whe n animals swallowed cysts. however. sinensis49. Thus . but not in the biliary tree. when he reported his second case in 1878 46. the weight of evidence favours the direct lumina l route. by ingestion of undercooked fish which had been imported from China. worms were found in the duodenum. While the route of migration was of great interest to parasitologists. Once flukes have reached the biliary system. Trichuris and hookworm disappeared spontaneously.148 A History of Human Helminthology (the earliest time at which he looked). some investigators have cast some doubt upon this route o f migration. then by 48 hours after infection had all migrated into the biliary tree 15. The worms were shown t o induce an epithelial proliferation and crypt formation in the extrahepatic bile ducts. Nevertheless. the words "its small pathological importance" 20. worms have occasionally been found in the pancreatic ducts. luminal enlargement and thickening of the walls of the intrahepati c ducts. cholangitis and cirrhosis in clonorchiasis. be more substance in the suggestion of a causal relationship between clonorchiasis and carcinoma of th e bile ducts 17. these signs could also have arisen as a result of complications of the Clonorchis infection or from a co-existent illness. RECOGNITION OF THE CLINICAL FEATURES Although the first patient reported with clonorchiasis had features clearl y referrable to the hepato-biliary system. Attempts have been made from time to time to associat e clonorchiasis with cancer. most patients having die d accidentally. Although flukes generally live in the bile ducts. the infection was discovered incidentally at autopsy. There may. sinensis. I am still unable to say whether C.nothing by which the disease can b e . When he described his second cas e three years later. periportal lymphocytic infiltration and fibrosis. Mebius gave a detailed pathological study of clonorchiasis seen in Chinese in Indonesia 48. In all of these individuals. biliar y obstruction. and the conclusion was drawn that bodily damage may b e considerable even though symptoms were abs ent or slight. but this association was almost certainly coincidental since both conditions are ver y common in eastern Asia. having both fever and jaundice 45. although I a m inclined to think that it in very old people the enlargement of the bile ducts may help in the production of gall-stones. More recent studies such as those of Hou 23 have defined the incidence of gall-stones. Watson-Wemyss in 1919 reported the coexistence of carcinoma of the liver and clonorchiasis in a Chinese soldier 72. McConnell remarked that: I am inclined to believe that there do not exist any special symptoms o f liver infection by these flukes .000 post mortems in Cantonese. the first such patient being described b y Sambuc in 191364. however.000 flukes weighing approximately 300 g were recovered from the liver and biliary system65. but the absence o f controls has not allowed adequate evaluation of the role of Clonorchis in the genesis of these conditions. 20 and adding as an addendum to the title of his paper on clonorchiasis. it gradually became clear that serious damage could b e caused by C.Clonorchiasis 149 After doing more than 3. and atrophy of live r parenchymal cells. These features were interpreted as indicating hyperplastic cholangitis with chronic fibrosing hepatitis. sinensis ever produces disease in them. In 1920. particularly in heavy infections. Similar changes were also noted by Hoeppli (1933) in a series of 66 patients 21. Perhaps the mos t massive infection on record is that described by Sambuc and Beaujean i n which 21. this symptom resolved 5. Indeed. USA. Although he considered that cholelithiasis. The onset of illness was variable. althoug h Roux and Tardieux (1912) appear to have been amongst the earliest 61. it is perhaps more likely that an improved diet while in hospital may have replenished a deficiency of the vitamin. splenomegaly and an eosinophilia in 10-40% of them. Banti's disease. 46 The question of the clinical manifestations of C. which occur commonly in refugee camps and could have accounted for most of these effects. China when 20-30% of 20. A massive outbreak of clonorchiasis occurred in 1946 in Shanghai. He also suggested that flukes might cause nigh t blindness. Thus. sinensis infection was taken up by Oldt in 1927 in a paper entitled "Is clonorchiasis a health menace i n China?"55. he concluded from his clinical studies that the presence of flukes did not ordinarily excit e symptoms. Ova can also be recovered from the upper gastrointestinal tract. n o significant differences were found between infected and uninfected persons 69. particularly in those wi th heavy worm burdens. sometimes insidiously. The passage of eggs in the faeces provides a simple method of arriving at the diagnosis. While it is conceivable that biliar y obstruction by flukes could impede the absorption of vitamin A and thus produce night blindness. particularly if the worm burden is not high. C. and felt that there was no group of symptoms that could properly be called typical of clonorchiasis. DEVELOPMENT OF DIAGNOSTIC METHODS The diagnosis of clonorchiasis was made initially at autopsy. but provided no data to support this contention. there are a multitude of other infectious agents. slight jaundice. This view is supported by the observations of Strauss w ho compared symptoms in 58 infected Orientals and 48 infected Caucasians in San Francisco. and concurrent inf ection with other helminths is likely to have caused an eosinophilia. after considering all the factors. While these manifestations may have been a consequence of clonorchiasis. sinensis eggs were found in the bile at cholecystostom y71 and in duodenal fluid obtained . This was associated in some patients with enlargement of a tender liver. It certainly seems likely that chronic Clonorchis infection does not cause significant symptoms. with those in a similar number of uninfected control subjects of both racial groups. with fever sometimes beginning abruptly. particularly vira l hepatitis. Eggs were found three to four weeks after exposure39. It is not clear who first made use of this technique in the living patient. One group was observed from soon after exposure then during the prodromal and acute phases. he believed that clonorchiasis was less harmful than ascariasis. Berkowitz working in Korea (1931) believed that the commonest features of clonorchiasis were indigestion and an enlarged liver.150 A History of Human Helminthology recognised during life. carc inoma and liver disease with ascites were m ore common in patients with Clonorchis infections. for when flukes were removed by drainage with duodenal tubes left in situ for days.000 Jew ish refugees became infected after eating pickled fish. may give a picture of structural damage consequent upon the infection 57. . and hetol76. Similarly. although not providing an aetiological diagnosis. THE SEARCH FOR EFFECTIVE TREATMENT Initial attempts to treat clonorchiasis were based upon the principle of firstly stimulating liver secretions (hopefully) by the administration of such agents as calomel. gold . Radiological investigations such as oral cholecystography and intravenous cholangiography. subsequent workers have found that praziquantel to be the most effective. Similar results have been reported b y other investigators 2. then secondly. Choi and his colleagues.Clonorchiasis 151 by duodenal intubation 5. Although Wang and his colleagues compared praziquantel. but these tests are usually normal in persons with light infections. fouadin . Needless to say. Direct surgical intervention wit h flushing out of flukes by drainage of the gall bladder was also tried o n occasion54.77 but the effectiveness of these drugs left a lot to be desired and their toxicity was a serious problem. the remaining five patients were cured by a second course of treatment and there were few side-effect s apart from headache and dizziness 60. urotropin and sodium salicylate in order to expel the parasites from the bile duct mechanically. but the side-effects of such a procedure were somewhat severe 5. for example. 68 58 29 4 32. Immunodiagnosis has not been of great value. In the following year. Rim and his colleagues treated 35 patients with three doses of praziquantel on a single day and cured 30 of them. Ryuji extended these observations in both humans and experimental animals and concluded that the established methods of faeca l examination for ova were both more reliable and easier 62.59 neostibnal . particularly in patients with heavy infections or bacterial complications. Thus.71. A number of specific anthelmintics have been advocated. Kuwabara and Muto in 1921 found that the complement fixation reaction was positive in a patient wit h longstanding clonorchiasis but negative in a patient with recent infection 41.56 has been claimed for tartar emetic 8. gentian violet . found no significant differences between asymptomatic infected persons an d uninfected control subjects 10. Bercowitz proposed prolonged duodenal intubatio n and suction in order to remove a dult worms. obtaining their removal from th e intestines by prescription of purgatives and enemata 61. Functional damage may be indicated by liver function tests. hexachloroparaxylol . amoscanate and hexachloroparaxylol in 98 patients in China and concluded that hexachloroparaxylol was the drug of choice70. arsphenamine . Some efficac y 66 14. The recent introduction of praziquantel (see chapter 3) has provided a safer and more effective drug.22. these measures were not particularly effective. chloroquine . in the farmers who raised the fish in fresh-water ponds . The Vietnamese commonly ate fish raw. Ijima first demonstrated that there was an anima l reservoir of infection when he dissected three cats in Tokyo and foun d C. The explanation of this phenomenon was furnished by Kobayashi's discovery in 1911 of fish being the second intermediate host of C. For the same reason. The infection was common. sinensis became understandable and fears that clonorchiasis might be introduced and spread in . filletted. however. then the feaster when he felt so disposed. He concluded that "It thus stands beyong doubt that Dist. The importance of cats and dogs in th e maintenance of the life cycle was revealed when it was shown that these animals were heavily infected in central China and that approximately 30% o f them were so infected in northern China 13. sinensis in various species of fish frequently eaten in Canton. wrapped in some aromatic leaf an d eaten. 11% of dogs and 33% of cats were infected. sprinkled with rice or grated sesame. the restricted distribution of C. sinensis 35. for only in southern China was it the custom of humans to eat fish raw or undercooked.38. an d subsequent workers defined several other susceptible species of molluscs in limited geographical areas. Finally. Amongst towns-people. mixed with powdered ginger. Kobayashi showed tha t a wide range of carnivorous animals was susceptible to infection 36. however. carefully dried between two bits of paper. were placed in a bowl and allowed to swim about. custom favoured infection in Vietnam where 1-40% of humans. f ished for it with a scoop. the distribution o f clonorchiasis in animals and humans did not always coincide. cut into pieces 1-4 cm long. The larger kinds were scaled. seasoned it. This was because the price of fish was so high as to preclude its being fed to these animals. when Muto (1918) found the missing link in the chain b y discovering that Bithynia striatula was the first intermediate host. Subsequently. cleaned. Small fish such as Carassius auratus. the infection was mo re common in the wealthier business people because the poorer classes could not afford to buy the food. sinensis in two of them. the majo r endemic area in China.152 A History of Human Helminthology UNDERSTANDING THE EPIDEMIOLOGY The major factors underlying the epidemiology of clonorchiasis were discerned only gradually. the infectio n being infrequent in humans in central China and unknown in northern China. Similarly. Oldt analysed the prevalence o f infection in this region in detail and showed that 20-30% of humans were infected whereas cats and dogs were only slightly infected55. endemicum infests not only the human liver but also cats" 30. whereas it was common in southern China. dipped into an acid. They found that the number of cysts ranged from none to as many as 300 per fish 26. Hsu and Chow investigated the prevalence and intensity of infection with C. Nevertheless. and ate the fish while it was still wriggling 24. salty or sugary sauce. it was more prevalent in males than in females be cause raw fish were usually eaten in restaurants that women did not patronize. In 1887. Clonorchiasis new regions were assuaged. Consequently. It was clear that the infection could be prevented by proper cooking of fish. these have not been very successful. A few years later. Le praziquantel dans le traitement des distomatoses hépatiques extrême-orientales à Clonorchis sinensis ou Opisthorchis viverrini. Kobayashi realized this and observed the effects of preparing fish in the standard Japanese ways on the vitality of the enclosed cysts. but if the fish were kept at room temperature. the worms remained viable . aliens with clonorchiasis wer e excluded from Hawaii. Handbook of medically important mollusks of the Orient and Wester n Pacific. Finally. 153 THE EVOLUTION OF PREVENTIVE AND CONTROL MEASURES The possibility of preventing clonorchiasis was apparent immediately Kobayashi discovered that fish were the vehicle by which the worm was conveyed to humans. but for a variety of reasons. ABBOTT RT. and as experiments failed to incriminate native snails as intermediate hosts 73. AMBROISE-THOMAS P. the condition being classified as a "loathsome an d contagious disease". this restriction on immigration was relaxed i n 1927. Harvard College 100: 245-328. infection failed to develop. Thus. the young fluke s died when their host became putrid 38. Bulletin of the Museum of Comparat ive Zoology. 1981 . river fish should not be eaten unless fully cooked and that no unboiled water be used 67. Other control measures have been suggeste d such as sanitary disposal of human faeces 16 and attempts at snail control 67. REFERENCES 1. Bulletin de la Société de Pathologie Exotique 74: 426-433. but when the fish were cooked in water at 50-70 oC for 15 minutes. GOUVILLIER A. When whole fish were roasted over live charcoals or boiled in water for 15 minutes an d then fed to cats and rabbits. and many authorities recognized the need for intensive health educationa l campaigns to persuade the populace to reform their eating habits. one author suggested that public places and schools should be placarded wit h humorous posters24. Japan. Since the infection did not spread to humans in th e mainland USA or in Hawaii. WEGNER DG. Kobayashi found that larvae remained alive for several days when fish wer e refrigerated. Faust also showed that worms survived immersion in strong brine for 54 hours and drying for a similar period 13. officials of the United States government became concerned about the possibility of importation and spread of clonorchiasis in the USA whe n 20% of Chinese immigrants arriving at San Francisco during World War I were found to be infected 19. while in Okayama prefecture. 1948 2. a leaflet was dis tributed urging that for the good name of the prefecture. 1981 18. BORDES FP. Journal of Parasitolog y 53: 1150. 1883 4. CHOI DW. Clinical studies of human infestations with the liver fluke ( Clonorchis sinensis). HSU HF. Über einige neue Parasiten des Menschen. 1933 22. Journal of Tropical Medicine and Hygiene 2: 38-39. Annales de l'École Supérieure de Médecine et de Pharmacie Indochine 2: 96-103. DIETRICH M. Laboratory findings in symptomless clonorchiasis. The new human fluke. 1981 23. Distomatose hépatiqu e évoluant plus de vingt ans après l'infestation. American Journal of Hygiene 4: 241-301. China and southeastern Asia and other species of molluscs closely related to them. KIM JW. Korean Journal of Parasitology 8: 8-12. Experimental therapy i n Clonorchis infections. Journal of the American Medical Association 67: 1835-1836. KHAW O K. Médecine Tropicale 23: 139-142. Clonorchiasis in Chinese residents of Panama. High efficacy of praziquantel in the treatment of 22 patients with Clonorchis/Opisthorchis infections. GUNN H. Histological changes in the liver of thirty-six Chinese infected wit h Clonorchis sinensis . GALLIARD H. BASNUEVO JG. 1875 12. 1931 6. 1926 15. China Medical Journal 27 : 168-171. Lancet ii: 423. HORSTMANN RD. KE-FANG Y. II. FAUST EC. 1908 21. Proceedings of the Society for Experimental Biology and Medicine 23: 607-608.154 A History of Human Helminthology 3. Studies on certain problems of Clonorchis sinensis . Au sujet d'une coutume favorisant l'infestation des Indochinois par Clonorchis sinensis (Cobbold. Transactions of the Royal Society of Tropical Medicine and Hygiene 75: 814-824. 1934 25. BERCOWITZ Z. Some recent aspects of the epidemiology of Clonorchis infection in China. Clonorchis sinensis in Orientals arriving in the United States. Notes on larval flukes from China. BLANCHARD R. PARKS SB. HOUDEMEYER E. FAUST EC. 1916 20. Studies on Clonorchis sinensis (Cobbold) with a consideration of the molluscan hosts of Clonorchis sinensis (Cobbold) in Japan. 1875). Revista Kuba de Medicina Tropical y Parasitologia 5: 105-110. Un cas grave de clonorchiase traité par l'émétique. HOU PC. Proceedings of the Society for Experimental Biology and Medicine 23: 245-248. FAUST EC. BRUG SL. MARTIN M. 1963 8. FELDHEIM W. Recherches sur l'étiologie de la distomatose hépatique au Tonkin . 1913 26. Animaux parasites (Notice préliminaire). 1967 10. HOUGHTON HS. 1927 17. HEANLEY CN. China Medical Journal 39: 287-296. 1925 16. FELDMEIER H. Bulletin de la Sociét é Zoologique de France 20: 217. FLAVELL DJ. KHAW OK. CHOW CY. 1955 24. 1970 11. 1938 19. Berliner klinische Wochenschrift 20: 234-238. II. 1949 5. Bulletins de la Société de Pathologie Exotique et de ses Filiales 27: 21-23. The age incidence of 109 cases of Opisthorchis sinensis infection in Cantonese: its small pathologica l significance. Studies on some larval flukes from the central and south coast p rovinces of China. 1924 13. CAVALLO A. American Journal of Hygiene Monograph Series. BAELZ E. Cloroquina y clonorchiasis. 1921 9. 1895 7. VAILLANTA. HOEPPLI R. Notes on the life cycle of Clonorchis. Excystment phenomena in Clonorchis sinensis . Liver fluke infection as an aetiological factor in bile duct carcinoma of man. 1925 14. CALERO MC. pp 284. Chinese Medical Journal 47: 1125-1141. COBBOLD TS. American Journal of Tropical Medicine 11: 43-60. The pathology of Clonorchis sinensis infection of the liver. YUNG-AN C. Tropenmedizin und Parasitologie 32: 157-160. FAUST EC. KHAW OK. Journal o f Pathology and Bacteriology 70: 53-64. Number 3. FAUST EC. . Bulletins de la Société de Pathologie Exotique et de ses Filiales 14: 161-162. (Is immunization possible in liver distomiasis?) Chu o Igakkai Kw. 1921. LI SY. MOTT JE. 1877 MEBIUS J. Imperial University. In Japanese KOBAYASHI HARUJIRO. Chines e Medical Journal 84: 8-16. Chinese Medical Journal . Geneeskundig Tijdschrift voor Nederlandsch-Indië 60: 224-294. Annotationes Zoologicae Japonenses 271-277. 1937 HSU HF. 1963 KEAN BH. 31. Notes on Distoma endemicum . Parasitenkunde und Infektionskrankheiten. 202. 1912. Supplement 3: 241-243. Lancet ii: 271-274. Leuckart). WANG CN. CHI N CM. 1925 KOBAYASHI HARUJIRO. Centralblatt für Bakteriologie. TU SF. Studies on ce rtain problems of Clonorchis sinensis . VIII. Bithynia fuschsiana . 1978 KHAW OK. 39. 1920 MOORE D. Supplement 3: 244-254. pp 677. Public Health Reports 39 : . 44. 36. In Japanese JOHN L. 49. 1915. The hatching pheno mena of Clonorchis ova. Observations on the epidemiology of infections with Clonorchis sinensis. Ein Hand. IX. Studies on certain problems of Clonorchis sinensis . 1966 KUWABARA S. 41. 47. pp 4. RUSSELL AJ. Cornell University Press. 42. pp 882. Abteilun g originale 75: 299-317. Unpublished report to the Colonial Office. 1940 HUECK O. 1907 McCONNELL JF. 1878 McGREGOR W. Ithaca. Clonorchis and clonorchiasis. CHANG TF. WEN HH. 1915 KOENIGSTEIN RP. 46. 45. FAN KC. 33. SUN KJ. C F Winter'sch e Verlagshandlung.Clonorchiasis 155 27. 1878. Saikingo Zasshi No. Report on an exp edition to China to study the trematode infections of Man. Igaku Zasshi (40): 20-26. Annals of Tropical Medicine and Parasitology 1: 123-152. Abstracted in Japanese Journal of Medical Science 1: 145. Hexachloroparaxylol in the treatment of clonorchiasis sinensis.und Tropen-Hygiene 42: 25-27. Archiv für Schiffs. A preliminary report on the source of the human live r distome. Transactions of the Royal Society of Tropical Medicine and Hygiene 42 : 503-506. A new form of paralytic disease associated with the presence of a new species of liver parasite. Journal of the College of Science . On some parasites in the museum of the School of Tropical Medicine . 48. Leipzig. The migration route of its larval stages in the snail. Experimental proof of Bithynia longicornis as the first intermediate host of C. 1886 ISHIZAKA K. 38. Classi c investigations. Lancet i: 406. TSENG FJ.und Lehrbuch für Naturforscher und Aertze. Chinese Medical Journal. Clonorchiosis hepatis. 1915 LEUCKART R. 1912 KOBAYASHI HARUJIRO. Zur Fuadinbehandlung bei Opisthorchis sinensis . 1940 HSU HF. In Japanese. Die menschlichen Parasiten und die von ihnen herrührende n Krankheiten. volume 2. Clonorchis endemicum (Bälz)(Distomum spathulatum . Note on the longevity of Clonorchis sinensis . 34. Remarks on the anatomy and pathological relations of a new species of liver-fluke. Zasshi Nagoya pp 34-45. pp 1-66. Proceedings of the Society for Experimental Biology and Medicine 22: 564-566. 1922 LEIPER RT. 35. 1938 IJIMA I. two volumes. Liverpool. 32. Far Eastern Association of Tropical Medicine: Transactions of the Second Biennial Congress. 29. Hong Kong. with English summary KOBAYASHI HARUJIRO. cirrhosis parasitaria en typische groei van het galgangepitheel. Investigation in the chief endemic centre of China. Glasgow Medical Journal 9: 3-15. MUTO M. Advances in Parasitology 4: 53-106. Tokyo 1: 47-59. On the life history and morphology of Clonorchis sinensis . 28. 1867-1876 LOOSS A. In Japanese. TU CC. 1875 McCONNELL JF. (A preliminary report on the source of the human live r distome. Chinese Medica l Journal 51: 341-356. 37. 43. Tropical medicine and parasitology. 1949 KOMIYA Y. 40. Abstracted in Tropical Diseases Bulletin 6: 295-296. Clonorchis endemicus [Bälz][=Distoma spathulatum Leuckart]). sinensis. 1911. 30. pp 108-112. LI SY. the Canton area. Baelz. "Distoma sinense" (McConnell). (The internal organs of Clonorchis sinensis ova and the morphology of th e miracidium). Prevention of distomi asis hepatis as carried out in Okayama prefecture. 1912 62. In Russian. Clinical evaluation of the therapeutic efficacy of praziquantel (Embay 8440) against Clonorchis sinensis infection in man. 1962 70. (Experimental study on the transmigration route of the liver distome in the body of the final host). Is clonorchiasis a health menace in China? China Medical Journal 41: 185-204. QIU ZD. TARDIEU. MUKOYAMA T. 1921 52. In Japanese . JOO KH.un d Tropen-Hygiene 39: 99-106. Archiv für Schiffs. 1926 69. 1913 65. In Japanese. KANDOU R. Tokyo Igakkai Zasshi 12: 579-587. SAITO S. 1922 54. LEE JS. Contributo allo studio delle sindromi d a "Clonorchis sinensis" nell'esturio dello Yangtzekiang e nella zona di Shanghai (Cur a chirugica con fistola biliare terapeutica). Annali di Medicina Navale 53: 59-78. SHIRAI M. (Diagnostic value of complement fixation in distomiasis). Japan Medical World 2: 224-226. OTTO JH. RIM HJ. 1981 61. SHIMUZU K. American Journal of Tropical Medicine and Hygiene 11: 625-630. RYUJI S. 1948 55. Abstracted in Tropical Diseases Bulletin 19: 651 . 1918. SINOVICH LI. 1935 59. Verhandlungen der japanischen pathologischen Gesellschaft. No. 1937 68. LIU JB. Distomatose pancréatique. Meditsinskaya Parasitologiya i Parazitarn e Bolezni.un d TropenHygiene 41: 296-302. WANG QN. Bulletin de la Sociét é Médico-Chirurgicale de l'Indochine 4: 425-429. TSCHAN TJ. 1922 51. CHEN RX. NARDONE PM. Translated in 33 53. 1927 56. Preliminary communication). ROUX. 1913 66. MUTO M. MUTO M. 1927 57. Tokyo 8: 151. Clinical manifestations of clonor chiasis . Geneeskundig Tijdschrift voor Nederlandsch-Indië 67: 59-63 . Partly translated in 33 64. pp 301-302. No. Un cas de distomatose hépatique ( Opisthorchis sinensis ) chez une Européene. Ueber de Behandlung der menschlichen Infektion mi t Clonorchis sinensis (Kobbold) mit Goldeinspritzungen. 1923 67. KAWADA T. 1924 50. OLIVIER PH. 1918. MUTO M. Chines e . American Journal of Tropical Medicine 3: 475-494. Journal of the Public Health Association of Japan 13: 1-4. Comparison o f praziquantel. QU ZG. Aichi Igakkai Zasshi 29. Okayama Igakkwai Zasshi No. Zur Frage der röntgenolo gischen Erkenbarkeit krankhafter Veränderungen am Magen-Darmkanal bei Patienten mit Opisthorchis sinensis . 1922. 1937 58. with English summary 60. 1898. 3: 49-52. 2. amoscanate and hexachloroparaxylol in clonorchiasis sinensis. Scientific Reports of the Government Institute of Infectious Diseases 5: 633-645. SAMBUC E. Abstracted in Tropica l Diseases Bulletin 17: 49. BAUJEAN R. OLDT F.a controlled study of 105 cases. La distomiasis sinense. OTTO JH. PLOTNIKOV NN. Bulletin de la Société Médico-Chirurgicale de l'Indochine 4: 331-333. (On the primary intermediate host of Clonorchis sinensis ) Chuo Igakkai Zasshi 25. In Japanese. Annals o f Tropical Medicine and Parasitology 75: 27-33. 1922. On the duration of life of Clonorchis sinensis infecting the animal body.156 A History of Human Helminthology 18021803. Archiv für Schiffs. SAMBUC E. 1922 63. Ueber den ersten Zwischenwirt von Clonorchis sinensis . Un cas de cachexie aqueuse chez l'homme (distomatos e hépatopancréatique) avec syndrome pseudo-béribérique. LYU KS. STRAUSS WG. Studies on the tr eatment of experimental liver distomiasis with "Neostibnal". 1964. Bulletin de la Société Médico-Chirurgicale de l'Indochine 3: 528-532. De behandeling van Clonorchiasis sinensis me t Gentiaanviolet Grübler. Results of treatment for clonorchiasis. In Japanese. (Experimental therapy of clonorchiasis wit h hexachloroparaxylol. 384. SHATTUCK GC. Abstracted in Japan Medical World 2: 243. LIU YH. KOYAMA H. with English summary 78. YOSHIMURA H. A preliminary note on th e investigation to determine whether clonorchiasis may be disseminated on the Pacifi c Slope. Public Health Reports 39: 861-862. II. Chemotherapy of Clonorchis sinensis . Proceedings of the Medical Association of the Isthmus Canal Zone 10: 130135. In Japanese. Clonorchis sinensis infection of the gall bladder and biliary passages with report of a case. I. YOKOGAWA M. An investigation to determi ne whether clonorchiasis may be disseminated on the Pacific slope. 1957 76. 1923 74. sinensis infection 1922 Mukoyama confirmed the larval migration route suggested by Kobayashi 1940 Hsu and Li showed that miracidia hatch only in the alimentary canal of susceptible snails and described their development in molluscs 1981 Various investigators report ed that praziquantel was the most effective drug for the treatment of clonorchiasis _________________________________________________________________________ 1874 1887 1911 . YOSHIMURA H. 1965 Table 6. Spontaneous hatching of Clonorchis ova. Journal of Parasitology 51: 961966. 1965.Clonorchiasis 157 Medical Journal 93: 849-856.1.4-Bis-Trichloromethylbenzo l [Hetol] for animals infected experimentally with Clonorchis sinensis . Japanese Journal of Parasitology 14: 526-533. Edinburgh Medical Journal 22: 103-104. LEPES TJ. WAYSON NE. The life cycle of Clonorchis sinensis : a comment on the presentation of the seventh edition of Craig and Faust's Clinical Parasitology. (Chemotherapy o f Clonorchis sinensis infection. Observation on the route of migration in the definitive host. Landmarks in clonorchiasis _________________________________________________________________________ McConnell discovered adult worms in the bile ducts of a human Ijima found the parasite in cats Kobayashi discovered the second intermediate host by feeding cyprinidine fis h infected with certain cysts to cats then recovering adult worms 1912 Roux and Tardieu diagnosed cl onorchiasis in a living patient by finding eggs in the faeces 1915 Kobayashi suggested that larvae migrated from the gut directly into the biliar y system 1918 Muto discovered the first intermediate host by incubating naturally infected snails with fish then feeding the fish to dogs then finally recovering adult worms 1918 Muto infected a snail with a miracidium and found a single sporocyst 1920 Mebius emphasized the possible pa thological consequences of C. Carcinoma of the liver associated with infection b y Clonorchis sinensis . YOKOGAWA M. WATSON FC. 1965 77. WATSON-WEMYSS HL. American Journal of Tropical Medicine 3: 461-473. Clinical observations on the treatment of clonorchiasis patients with 1. TSAI CS.) Japanese Journal of Parasitology 14: 233242. 1924 75.4-Bis-Trichloromethylbenzol. Studies on Clonorchis sinensis . 1980 71. 1919 73. Chemotherapy with 1. WAYSON NE. WYKOFF DE. I. 1917 72. American Journal of Tropical Medicine and Hygiene 6: 1061-1065. . was able to perform a post mortem examination without incurring the wrath of the Chinese who wer e extremely prejudiced against mutilating the human body after death.Chapter 7 Paragonimus westermani and PARAGONIMIASIS SYNOPSIS Common name: lung fluke Major synonyms: Distoma ringeri. On ingestion by a human. westermani Distribution: eastern Asia (related species are found in West Africa) Life cycle: the ovoid flukes. a parasite in the lungs . pulmonale. consulted Manson about an eczematous 159 . A t autopsy. who was a secretary in a mandarin's office. Since the dead man had been a patient of Patrick Manson's in Amoy. mongoose etc Major clinical features: fever. Dr BS Ringer. a Portuguese resident of Tamsui. praziquantel DISCOVERY OF THE ADULT WORM In June 1879. The ova develop in water over two weeks then each miracidium escapes and invades snail intermediate hosts of the genera Semisulcospira and Brotia. The emergent cercariae invade the gills then the muscles of a number of freshwater crabs and crayfish where they encyst. if I remember aright. Since he was a foreigner. Chin a during November and December of the previous y ear. and. slight congestion of the lungs. Ringer wrote to Manson detailing his findings. There were some small deposits of tubercle. a 35 year old Chinese man. live in cavities in the lungs and produce eggs which are coughed up in the sputum. With respect to the worm. The miracidium becomes a sporocyst which produces rediae then cercariae. Ringer found. dyspnoea. pleural aspirates or faeces Treatment: bithiniol.it might have escaped from a bronchus. the local physician. in addition to the aneurysm. he wrote: After making a section I found the parasite lying on the lung tissue . cats. Whilst alive a number of young (microscopic) escaped from an opening in the body. Formosa (Taiwan) die d suddenly from a ruptured aneurysm of the ascending aorta. cough. abdominal discomfort and epilepsy in heavy infections Diagnosis: demonstration of eggs in sputum. 7-12 mm long by 4-6 mm wide and thick. the enclosed metacercariae excyst in the duodenum. dogs. no cavities. D. D. sputum. migrate through the intestinal wall to the peritoneal cavity then pass through the diaphragm and the pleural spaces to the lungs where they mature in cysts or "capsules" over two to three months Definitive hosts: humans. 104 On 24 April of the following year (1880). Manson realised that it was a trematode.No distinctly organised embryo could be made out in the uninjured ovum. he was seized by a fit of coughing and expectorated small quantities of reddish sputum . but when the contents were expressed..68 Cobbold communicated news of the discovery to the meeting of the Quekett Microscopical Club on 25 June 1880. In order to exclude accidental introduction of ova in food. and granular matter having very active molecular movements. besides ordinary blood and mucus corpuscles. the shell being left empty and fractured at the opercular end. a place about two days' journey from Tamsui. an d dimensions as those I had some time before found in the Chinaman' s sputum. Manson (who at that time was trying to find the daytime location of periodic microfilariae) placed some of this material on a microscope and was astounded to find that instead of the anticipated microfilariae. Accordingly. probably in the lungs. it: contained. and there announced his intention t o name the fluke Distoma ringeri after its discoverer. leathery texture. Moreover. colour. measuring on an average 1/300" x 1/500".evidently a fluke . they resolved themselves into oil masses.160 A History of Human Helminthology eruption on his face and legs. granular on the surface."69 The parent parasite was light brown in colour. of a firm. He wrote in his diary at this time that "I cannot but think that the parent of the ova and th e haemoptysis are associated as cause and effect" 72. one end of the oval being cut off by an operculum. He had lived in a town called Tacktc ham.. large numbers of bodies evidently the ova of some parasite.and also a sample of the Chinaman's sputum. bloodstained. the attacks of haemoptysis had begun after he had been on that island for about a year. Manson examined the oral cavity caref ully but failed to find such a parasite. and measured nearly half an inch in length. and that I had stumbled on a new disease. I turn to you for more information. Manson placed a little of the sediment in the spirit under a microscope and "found in it several ova of the same shape. Several years later he recalled that "I concluded that a parasite must reside somewhere below th e vocal cords. I send the worm . he obtained a fresh specimen of sputum two days later and confirmed the presence of eggs. These bodies were oval in form. sent it to Spencer Cobbold in London together with a covering letter dated 4 May 1880 saying: I could not find in your 'Parasites' a worm to correspond. The first notice of thi s event appeared in an abstract in The Lancet of 3 July 1880 13 then Manson's . Firm pressure on the covering glass caused them to rupture and their contents to escape. and as I have some idea that the worm is not an unfrequent cause of haemoptysis in Chinese." 71 Further enquiry revealed that the patient had o nly been in Amoy for one year. 69 Concerned that there might be a parent worm in the mouth or throat. he wrote to Ringer who s ent him the solitary specimen preserved in "spirit of wine". but being unsure of whether or not it was a new species. and this reminde d Manson of the parasite discovered by Ringer. While the patient was speaking. He was a native of Foochow in China but fifteen years previously he had gone to Taiwan to live and had remained there for nearly ten years.. Japan. by Erwin Baelz. while awaiting Leuckart's reply. protozoa). They have an sharp.07 mm in width. which shimmers greenish or reddish. Manson read this and recognized the likely connection between the eggs h e was studying and the parasite found by Bael z. Meanwhile. When flattened on a glass slide. Since psorosperms were thought at tha t time to be a stage in the development of gregarines (i. had come to the same conclusio n himself.(2) motionless balls . and occupied fully four-fifths of the body. Baelz sent specimens containing these bodies to Leuckart in Germany who pronounced them to be eggs of a trematode.16 He believed that the larger bodies were psorosperm cysts and that the smaller balls were immature psorosperms. Soon after his arrival. doubly refractile shell.. Baelz in his first publication stated that he: wish(ed) to name this disease Gregarinosis pulmonum and the parasite Gregarina pulmonalis. and was retold in The Lancet in 1883 71. he became in terested in a respiratory disease that had been mistaken previously for tuberculosis. Cobbold added that he had now viewed the worm sent to him by Manson: I satisfied myself that the fluke was new to science and accordingly I propose to call it Distoma ringeri after the discoverer.. Baelz. and in Manson-Bahr 73): Dear Dr. Though mutilated. He described these organisms as being of two forms: (1) as intensive yellow-brown. here the cyst of the "egg" opens. oval bodies. An abstract of Baelz's report appeared in The Lancet of 2 October 1880 13. as also were traces of an organ which I regarded as the remains of the ventral acetabulum. to send you a .13 mm in length and 0.At the blunt end a kind of cover is often found. because of its color. the oral sucker was well shown. I always waited for a good case of the Haemoptöe parasitica. as is indicated in his letter to Manson quoted below. He therefore wrote to Baelz who sent him some sputum containing the bodies. the same eggs had been seen in 1878 in Tokyo. Baelz had gone to Japan from Germany in 1878 as a lecturer at the Imperial University i n Tokyo.having no shell and measuring 0. In September 1880.. or perhaps also.36 Manson's detailed account of the ova and clinical aspects of the case appeared in the Medical Reports of the Imperial Maritime Customs (China) 69.02 mm thick. Manson. In the meantime. 0... 0. Bael z reported that he had seen 19 patients with haemoptysis in whose sputum h e had found parasites.. together with an accompanying letter dated 19 February 1881 (publ ished in Manson-Bahr and Alcock 74 where it is misdated as 1880.First of all I have to apologize for not having written to you earlier. was reproduced in the Medical Times and Gazette in 1881 69. lying deep under the dermal surface. the capsules of the vitellarium were well seen.e.Paragonimiasis 161 letter to Cobbold was published in the Journal of the Quekett Microscopical Club the following month 68. although he failed initially to recogniz e their true nature. The contents consist of a viscous gelatin in which three to five (most often four) lumps are embedded. which many years ago I detected in the lungs of an Indian ichneumon.. . In an Appendix to this paper.04 mm in diameter..01 to 0. but it is much larger and evidently a distinct species.. The worm reminds me very much of the Distoma compactum.16 Soon afterward. Gregarina fusca. a royal tiger had died in th e Amsterdam Zoological Gardens in Holland in September 1877. and feel only too well that I always make mistakes. Near the end of 1880. and trust you will be able to compare the eggs in the sputa with those which you found in the lung of a patient affected with distoma. At autopsy. the Japanese investigator. In November 1881 in the same hospital. which were nearly one centimetre long. I wrote this to Leuckart. and if so. I have not much practice in writing the language. Detailed examination revealed that this was not so. Dr CF Westerman. he found that the bodies were identical in every respect with those coughed up by his ow n patient and with those expressed from Ringer's fluke 70. but now when I send my first notice of them to Europe. he sent several worms to Baelz in Tokyo with the suggestion that they be named Distoma pulmonalis. Kerbert described th e worms. who had been a medical student at Tokyo Imperial University and a pupil of Baelz. there could hardly be question of another than distoma. I had called them Gregarinae. fibrous capsules. naming the worm afte r . each containing one or two worms. and Kerbert recorded the discovery in 1878. which. however. and he too is of the same opinion. always in pairs. pulmonale 17. inside rather thick. even though he must have known that Cobbold had called the same parasite D. Nakahama and Suga carried out a second autopsy and obtained several more worms. These helminths were sent by the director of the zoo. and found 52 cases of the infection. rude) and in an Indian mongoose by Cobbold in 1859 (D. to the Dutch zoologist Coenraad Kerbert for further identificaton. because of the somewhat blue color. In March 1883.162 A History of Human Helminthology specimen. He surveyed patients who came to the clinic of the Okayama Prefectural Hospital between November 1880 an d October 1882. 49 Since flukes had already been found in the lungs of an otter by Natterer an d described by Diesing in 1850 (D. Nakahama tried to study the morphology of these worms but they had shrunk so badly in alcohol that it was impossible t o discern details of their structu re. worms thought to be a species of Distoma were found in the lungs. then Baelz prepared a report (published in a German journal) in which he named the species D. Before all these events occurred.. Drs Kiyono. Nakahama. ringeri. It is not at all improbable that you will find them identical.. compactum). Nakahama published his findings in four parts between February and September 1883 94. It was now clear that Baelz's Gregarina pulmonalis were none other than ova of the fluke named D. as being: found. Nevertheless. went to Okayama in Japan to study the disease. I saw some cases what seem to me to prove that the oval bodies must be eggs of some worm.S. P. because they are exactly what is described as such. Kerbert thought that this trematode migh t prove to be one of those species. ringeri by Cobbold. At last I have got a prominent one. were noticed immediately on the outer surface of the lungs. 18 When Manson examined the specimens sent to him by Baelz. Suga and Yamagata performed their first autopsy on a patient with parasitical haemoptysis and found about 20 cysts.. I ask your pardon for my bad English. and the parasite became known as D. Much was expected of him as he was the first Japanese to receive such an extensive parasitological training. is now generally admitted to be identified with Kerbert's form from the tiger. sp"49. this name was relegated to synonymy. such as that written by Paul in Japan: 'Distoma pulmonale' is the best name. however. Leuckart wrote that in his and Nakahama's opinion. in introducing this unknown worm to zoologists as Distoma westermanni. with the forms westermanni. later returned to Japan and was awarded the degree of doctor o f medicine by Tokyo Imperial University. and they compared them with the Japanese flukes. Since Kerbert's description had priority. westermanni. incidentally. therefore. although there were pleas to the contrary. and a similar parasite was found in its lungs. The name Paragonimus was derived from the Greek words (PARA) meaning "by the side of" and µ (GONIMOS) meaning "gonad" or "genitalia". enabling him to undertake an intensive morphological study50. but he soon abandoned this vocation and took up a position as chief of the medical section of the Nippon Life Insurance Company. ringeri and Baelz's D. and even by the same author. Arthur Looss gave a detailed description. which was the most accurate and complete that wa s available for many years. He established the genus Polysarcus for the mammalian lung flukes 66. Later in the same year. and unaware of Braun's revision. making P. westermanii and westermani all being used by different authors. n. it raises no question as to priority of discovery. Cobbold's name of D. another tiger died in the Zoological Gardens in Hamburg. This view became accepted and Stiles and Hassa l voiced the general opinion when they stated that the human parasite "though originally supposed to represent a new species. pulmonale lapsed. but because of its slightly later appearance. the European and Japanese forms of th e worms were identical 64. This material was also forwarded to Kerbert. The specimens studied by Kerbert were re-examined later by Leuckart and Nakahama (who had gone from Japan to study parasitology in Germany with Leuckart). Max Braun erected the genus Paragonimus for the mammalian lung flukes. westermani (Kerbert) the type species 21. Three years later. of the parasite. . In 1899. A number of authors realized that the morphological features of this fluke were so distinctive that it should not be retained in the genus Distoma. In 1889. and by its affinity with the names 'distoma haematobium' and 'distoma hepaticum' it aids the memory and pleases an orderly mind. eventually the last description became generally accepted even though Kerbert had first described it as westermanni. Germany.101 There was considerable confusion over the correct spelling of the specifi c name. 107.Paragonimiasis 163 Westerman and wrote: "I feel justified. Nakahama. Hungerford replied on 21 October 1881 and with remarkable prescience put his finger on the correct species: My dear Manson.It will be something in favour of my hobby.. westermani was finally determined. For about 18 months after his discovery of the eggs. he scrut inized sputa of about 150 persons in a fruitless search for more ova. Your discoveries about the lung fluke are decisively interesting. h e considered the possibility of a snail being the intermediate host. Unfortunately.. Manson realized that their contents wer e undeveloped. He wrote to R Hungerford.. As soon as he first saw the ova.164 A History of Human Helminthology ELUCIDATION OF THE MODE OF TRANSMISSION: DISCOVERY OF THE LARVAL STAGES AND THE INTERMEDIATE HOSTS Manson concluded his paper of 1880 by remarking that the questions of the existence and identity of the intermediate host or hosts of the parasite offered a very interesting field for further investigation 69. With great foresight. Let me know if you would like to have a few specimens in spirit and I will write to a friend in Nagasaki to send them down. He deduced that the infection was not endemic in Amoy.I have found none of this species in China.... I know of one fresh water species which I think answers all your requirements of 16 shells of which I am sending you from my collection in the mail.. He placed some phlegm in water jars in his laboratory. 38 The full significance of Manson's perspicacity is displayed when it is recalled that it was not until 1882 that Thomas and Leuckart demonstrated that Fasciola hepatica was transmitted by molluscs (see chapter 4).On the whole I think M. before the life cycle of P. Manson found that miracidia had developed and escaped from the ova by way of the opercula 70. he is a hardy beast and will reach you from Tamsui alive. He then forgot about the specimens for six weeks or so until his wife com plained of an odour emanating from the laboratory... Manson's observations on the development and hatching of miracidia were confirmed by Nakahama in 1885. The shell I speak of is Melania libertina (Gould). When he examined this material. a conchologist in Hong Kong for further information .. Libertina must be your friend. but rare on the Chinese mainland around Amoy..... the lack of potentially appropriate snails and the difficulty in obtaining a con tinuing supply of ova prevented Manson from pursuing the matter further. common t o Japan and Taiwan where parasitic haemoptysis appeared to be endemic. and any help I can give you in this matter is very much at your service. Almost 40 years were t o pass. and eventually obtained some fres h infected sputum from Taiwan which permitted him to continue hi s experiments. but the ova refused to hatch.. He reasoned that the intermediate host must be an inhabitant of fresh water. however.. however.It occurs in Japan at. the n examined them daily for the first fortnight or so. but no further significant advances wer e . if it helps clear up a doubtful point in the natural history of flukes.places widely apart. The smell was comin g from the decomposing sputum on which fungi of all descriptions wer e growing. he hoped that these would enable him to observe t he development of the larva within the egg and characterize the conditions under which it hatched. Nakagawa was convinced on morphological grounds that the larger cysts at least. In September 1914. The second dog died 90 days after eating infected crab. westermani. although they were insufficiently mature to produce eggs. he had to raise adult worms from them. Taiwa n where parasitic haemoptysis was endemic. straight body and an oval sucker with a spine. two or three P. Nakagawa at that time believed that both the large and the small cysts belonged to P. were stages in the life cycle of P. In October 1913.4 mm in diameter. He identified this creatu re as Potamon obtusipes. post-morte m examination showed the lungs to have a large number of cysts. gills and other organs of a crab harbouring numbers of encysted larvae to two puppies that had been obtained fr om an area where paragonimiasis was unknown. 0. One of the dogs died 60 days later. amphibians and insects that he could find. Koan Nakagawa.Paragonimiasis 165 made until the Japanese physician. two were fed with a large quantity of th e internal organs of infected crabs while the third was left as a control. He therefore fed the liver. he found both kinds of metacercariae in P. thick.2 mm in diameter. he captured a crab that was of type he had not seen before in a rivulet near Kalapai village. who had been appointed head of the public hospital in Shinchiku. He knew that an intermediate host was necessary for he ha d shown earlier that miracidia were incapable of developing in the definitiv e host. 89 The second form of encysted larvae measured 0. but the specific identity of which was uncertain . Continued searching. to seek the intermediate host o f P. with the smaller variety being merely younger stages of the larger. which were unmistakabl y half-grown trematodes. revealed the worms that he had been seeking: as a result of further investigation I found in the gills full-grown ones with all the morphologic structures peculiar to the distome of the human lung. Within each cyst. had a short. he had both fed puppies with miracidia and immersed them in water containing miracidia but had failed to find flukes in the dog s 45-100 days later90. westermani. He therefore collected and examined all the molluscs . Eriocheir japonicus. In the liver of this crustacean. the lungs of the dog were found to contain numerous cysts enclosing adult flukes ready t o discharge ova. westermani were present. and occasionally in another crab. He then repeated the experiment with three more puppie s brought from a nonendemic area. Nakagawa foun d numerous encysted larvae. At autopsy.3-0. reported his discoveries in 1915. dehaani. The first two dogs died about seven weeks later and were found to be infected wit h . rathbuni 53. westermani. fishes. Subsequently. however. but in order to prove the point. DISCOVERY OF THE CRAB SECOND INTERMEDIATE HOSTS The discovery by Kobayashi that freshwater fishes were the second inter mediate host of Clonorchis sinensis (see chapter 6) encouraged Nakagawa . although it was later shown to be P. westermani and the time when this was done. the smaller cysts could b e reared. Sesarma dehaani and E. I may say that of the three species of freshwater crabs. while the control puppy remained uninfected. Hungerford in 1881 suggested that M. imprecise or incomplete. In that paper. the exact distribution depe nding upon the species of crab 132. Furthermore. In Korea.55. Yokogawa based this conclusion upon the observation that the smaller cysts were sometimes found in regions where paragonimiasis was not endemic. at least partially. in mice and the resultant immature worms inhabited the bile duct and did not have a spine on the oral sucker. but the details of most of their experiments were unclear. The precise mode by which humans and animals became infected wit h P. This led to the assumption that infection may result from contamination of food and water by freeliving cysts discharged from infected crabs. libertina was a likely species. before he discovered cysts in the crab. westermani. a number of investigators realized that paragonimiasis sometimes occurred in regions where people did not take crabs as food134 or else they always cooked them thoroughly first 40 . Sadamu Yokogawa argued that the two forms of cysts found in the crab by Nakagawa belonged to distinct species. S Yokogawa and Yoshida. Subsequen t investigators added experiment to hypothesis. He fed cysts to three cats and a dog and eventually recovered adult P. westermani was a matter of some debate. to pinpoint precisely who first described th e primary intermediate host of P. westermani were Potamon dehaani. purely on the basis of circumstantial evidence.89 This discovery was soon confirmed by Ando. Matsui. Yoshida found that in Japan. As will be discussed later. if not impossible. the crayfish Astacus (Cambaroides) similis was also an intermediate host of P. The first person after Hungerford to close in on the molluscan intermediate hosts was Nakagawa. the species of crabs that were th e second intermediate hosts of P. These result s were first published in Japanese in 1915 87 then appeared in English in the following year 89. westermani 54. Hisao Kobayashi. cysts were found in the gills. Harujiro Kobayas hi found that in addition to E. he had made an extensive study of freshwater molluscs obtained from ponds an d . the encysted larvae of the human lung distomes are found in the first and second species.133. Nakagawa in 1917 accepted that Yokogawa's views were correct. japonicus. with the larger one being the intermediate stage of the lung fluke 127.166 A History of Human Helminthology Paragonimus. In 1917. Nakagawa summarized his findings thus: In conclusion. Indeed. japonicus. As described earlier. the occurrence in the third being problematical. While infection could clearly be acquired by eating undercooked crabs. muscles and liver of the crustaceans. DISCOVERY OF THE SNAIL FIRST INTERMEDIATE HOSTS It is difficult. all of whom reported their experiences in the same year (1915). obtusipes and 20 P. libertina living in the creeks of a highl y endemic area contained sporocysts in the liver and a particular cercaria which he then described. the few crabs found to have been infected may wel l have acquired their infection naturally in the wild. westermani miracidia in order to see which kinds of molluscs the miracidia would infect: It resulted that they infected Melania libertina Gould and M. It seems likely that they were the latter. Nakagaw a was convinced that he had demonstrated the life cycle of P. dehaani. westermani on a number of grounds. westermani.Paragonimiasis 167 streams in the region. westermani ova or whether they were naturally-infected snails. Again. Yokogawa in 1917 showed that the two types of cysts found by Nakagawa in crabs represented different species of flukes. he could find only three infected animals . but finally secured 50 P. From this it may be assumed that these two species of fresh water molluscs are the first intermediate hosts of the lung distomes. westermani belonged to some unknown fluke. Thi s confuses further the validity of the observations just described. it is uncertain whether the snails were infected experimentally or naturally. including the resemblance between the cercariae and the small type of cyst he ha d described in the livers of crabs. He had considerable difficulty in obtaining crabs free of flukes. When the remaining 30 crabs were dissected after a further three weeks. When Nakagaw a examined the crabs 36 days later. he attempted to establish the link in the life cycle between molluscs and crabs by infecting crabs with cercaria e derived from snails. Nevertheless. and in 1917 published his findings in the Journal of Experimental Medicine 90. tuberculata was also a likely vector. oblique-granosa Smith most abundantly. in which case the identity of the parasites is doubtful. Further. He found 17 different kinds of cercariae. Nakagawa added new data to his earlier observations and indicated that M. He wrote in 1916 that "it may not be unreasonable to conclude that these cercariae are tho se of the lung distome. Nakagaw a recognized he veracity of Yokogawa's assertions and admitted that the forms taken by him to be developmental stages of P. he found none of 20 P. He did find. but it is unclear whethe r these snails were infected experimentally with miracidia derived from human P. He therefore put various snails in wate r containing P. However. He published a detailed des cription of the development of larvae in the snails. dehaani infected. obtusipes and only one of 20 P. He thereupon published a new series of illustrations of th e . Indeed. He put these together with Melania snails in a stream on 4 September 1915 but was re warded with only scant success. 89 Nakagawa tried to keep the snails alive in an experimental pond but they all died within a few weeks and no fully-developed cercariae could be seen. It is probable that he was dealing with the latter case since he justified his assertion that the resultant cercariae were P. Nakagawa was uncertain why it was so difficult to infect the crustacean s experimentally. we have not yet any experimental proof" 89. As mentioned earlier. In 1917. that all the M. however. but could not distinguish those of the lung fluke. westermani. kellicotti) was carried through experimentally 3. westermani. E. genital openings and wounds on the surface of crabs. S Yokogawa and Wakeshima in 1934 still believed that there was no conclusive proof that Melania species were involved. japonicus and P. showed tha t under experimental conditions. extensa vigorously. He concluded cautiously that the genus Melania was probably concerned in the metamorphosis of Paragonimus 55. westermani all belong to the family . nodiperda var. for when cercariae obtained from s nails were fed to or injected into experimental definitive hosts.92 to replace the earlier series which had depicted both forms of larvae. He therefore put P. The redia e migrated into the deeper parts of the snail's body and formed secondgeneration rediae which in turn migrated into the liver and produced cercariae 56. and some of the parasites were induced to develop into adult Paragonimus when the infected crabs were fed to youn g dogs6 . dehaani. This technique was necessary because Yokogawa had found that cercariae were rarely shed from the snails under natural conditions. but the cercariae failed to develop or else the crabs died. the snails had been obtained from a n area that was highly endemic f or paragonimiasis. Similar experiments were performed and results obtained at almost the same time by K Miyairi78. paucicincta with P. P. therefore.93. libertina121. Kobayashi working in Korea. gills. a single redia was formed. Inconclusive attempts to passage P. in 1952. westermani miracidia reared from human sputum. Although Ando later contended that he had proved definitely that Melania libertina was the intermediate host of P. westermani by feeding the crabs with cercariae in the digestive glands of M. dehaani into a pool with snails heavily infected with cercariae. M Yokogawa succeeded in infecting experimentally P. The smaller cysts were subsequently identified as belonging to a previously undescribe d fluke. In 1918. quinaria and M. westermani miracidia attacked M. It was not until 1934 that the complete life cycle of any Paragonimus (P. Th e miracidia penetrated the skin readily and gave rise to sporocysts localized near the surface. westermani 14. He then examined the effects of infecting M. Ando also showed that a second intermediate host was necessary fo r maturation. that the second intermediate hosts were infected b y eating snails containing mature cercariae. libertina were also made by Kakami 40.168 A History of Human Helminthology various stages in the development of the larvae which form large cysts 91. Within each sporocyst. A Ando (also known as R Ando) took cercariae isolated from (probably) naturally-infected Melania and introduced them through the mouth. In a new attempt to prove that snails were the intermediate host of P. clarkii with P. westermani through M. they failed to develop 8. H e concluded. The snail intermediate hosts of P. M. Finally. Stephanolecithus parvus 92.79. for experimental infections had never been carried through from the miracidial through the cercarial and cystic to the adult stages using defined worms obtained from infected individuals 130. Many crabs became infected subsequently with P. gottschsei. operculate snails that live in fresh or brackish water. mostly within 48 hours. the members of this family that served as intermediate hosts for trematodes were assigned to the genu s Melania. Once the larvae had escaped from the cysts. however. 126 In the lungs. or through the mediastinal connective tissues. while Yamagiwa (1890) believed that direct migration from th e peritoneal cavity across the diaphragm to the pleural space and lungs wa s more likely119.Paragonimiasis 169 Thiaridae which contains several hundred species of large. they failed to complete their development. Ando and Tsuyuki recorded the case of a patient who still ha d eggs in his sputum 20 years after leaving an endemic area 10. Sometimes the migrating flukes took aberrant paths such as into th e abdominal wall where they moved about in the muscles and connective tissue planes. so it is impossible to assign priority to any particular individual. Thus. however. Abbott revised the nomenclature of these snails 1. are those of Nakagawa89 and Yoshida134 . the pathway of migration of larvae was determined independently and with incredible speed by f ive investigators. but the lungs seem to be the most . the larvae developed into adult worms and often persisted fo r many years. for example. since that time. Under these circumstances . Otani (1887) favoured the haematogenous route100. In the experiments performed by these tw o investigators. to the neck and head. usually that of the jejunum. Once the final part of the life cycle was discovered by Naka gawa. Even if they move into the parenchyma. with Ando 4. The most accessible of these papers. the route o f migration of P. they form the tiny vacuoles or tunnels. Fo r many years. In 1948. they penetrated right through the intestinal wall. particularly via th e perivascular sheaths. Nakagawa88. Each of thes e persons reported similar findings. Nakagawa wrote: These parasites can bore through various tissues and may reach other organs than the lungs.126 first reporting their results in 1915 and Yoshida 134 doing likewise in the following year. from that point.. westermani larvae from the mouth to the lungs was in doubt. however. STUDIES OF THE MIGRATION AND DEVELOPMENT OF LARVAE AND PATHOLOGICAL REACTIONS IN THE DEFINITIVE HOST For a number of years. but rather they penetrate the visceral pleura. Melania libertina. where they form their regular cysts. Hisao Kobayashi60.. and entered the peritoneal cavity. The larvae then travelled beneath the visceral pleura before burrowing into the lung parenchyma where cysts were formed and the worms matured.don't instantly penetrate the parenchyma.89 and Sadamu Yokogawa 125. They then crossed the abdomina l cavity and perforated the diaphragm to reach the pleural spaces after several days. As Yokogawa remarked: metacercariae. has been known as Semisulcospira libertina.. the young larvae penetrate freely into the tissues of the lung and form petechiae in many places there. dogs and cats were fed upon infected crab flesh then killed after varying periods. oedema and leucocytic infiltration which culminated in the formation of a fibrous cyst wall around worms 45.. Ando fed cysts repeatedly to dogs that were already infected with adult flukes. subcutaneous connective tissue. and Choy and Ludlow noted ova in a mass in the anterio r abdominal wall 28. helminths migrating through the body not infrequently left small haemorrhages marking their tracks. petechiae were noticed in the intestinal wall where larvae ha d presumably penetrated and a m ild inflammatory reaction in the serous cavities was evoked occasionally. the scrotum and brain. when puppies born of infected bitches were challenged.89 These views were echoed by S Yokogawa: metacercariae. congestion. orbit. In contrast to the above fact. showed that this was not always true. thus they stay there longer and produce those symptoms which initially attracted my attention to them as parasites. Pathological reactions in the definitive host were studied in experimenta l animals and in humans that came to autopsy. Kimuri found large numbers of eggs in the neighbourhood of cysts in the brain 52.are able to live and grow in connective tissues such as the mediastinum. In ectopic locations. thus the larvae might be destroyed by lack of nutrition. with attention being focused on both the worms in the lungs and those in aberrant sites. the greater omentum. Furthermore. Fo r example. eyelids. with a matrix of small blood vessels in the capsule and with openings into th e airways. and in the hilar lymph nodes. . Sometimes. Kau and Wu studied the histopathology of the lungs of cats infected experimentally and note d collapse. flukes failed to develop in the lungs. In order to determine whether resistance to reinfection could be induced in paragonimiasis.100. chronic inflam mation produced granulomatous tubercle-like lesions which sometimes suppurated.126 Subsequent studies. What is more a mechanical stimulation causes suppurative inflammation in the area. however. Thus. They don't have means of discharging eggs or ovulation. Similarly. Ando concluded that a n effective immunological response was mounted 9.86. Simila r changes were described in infected human lungs 37. they can never reach the perfect growth. Cysts about 1 cm in diameter were found more commonly in the deeper parts of the lungs. Ova surrounded by chronic granulomatous inflammation were seen in the walls of cysts.. In other organs. S Yokogawa 126 and other early investigators found that migrating larvae caused little reaction .170 A History of Human Helminthology favourable place for their development and the laying of their eggs. those parasites which reside in the lungs easily produce ova when the nutrients are provided. in th e bronchial mucosa and submucosa. He found that the number of flukes which matured declined progressively.. thus allowing egress of ova and any blood surrounding the worms. unmixed with mucus. Manson realized that recurrent bleeding might induc e anaemia in certain persons and expo sed them to the possibility of a dangerous. Lu and col leagues found that a productive cough. The importance of paragonimiasis as a cause of Jacksonian epilepsy was the n emphasized by Yamagiwa 119.Though rather thin. every second or third month. one having recurrent haemoptysis for 11 years and the other for four years 71. had similar symptoms.. Nevertheless.The patients show absolutely no symptoms except for occasional throat irritation and a completely untroublesome cough. although according to Katsurada 44. In a recent series. smaller in quantity. Tso-tong in detail: When he was 22 years of age. as in the former attack. who were servants of a friend of his on Taiwan. mesentery and cervical glands 100. but had very little cough. intestinal wall. westermani in the frontal and occipital lobes of the brain during the post-mortem examination of a man who had suffered from recurrent epileptic attacks. Most importantly. Otani in 1887 found cysts as well as eggs of P. but that no characteristic signs were present on clinical examination 67. 71 Clinical studies over the years have generally confirmed these observation s with the additional realization that secondary infection may be a distressin g complication of pulmonary paragonimiasis 20. he enjoys good health. very often for many years either frequently or intermittently. 69 Manson's next two patients. He has never had much cough. tuberculosis. Since then. Haemoptysis returned about six months later.. Everyday for 19 days he brought up from an ounce to half an ounce of blood. but I have no doubt that in time it will be found to operate prejudicially on the populations of the countries in which it is endemic. he emaciated slightly. he remarked I am not in a position to assign to this parasite its exact share among the causes of grave disease. He recognized that in contrast to that other prevalent cause of spitting blood. was first described b y Baelz in 1880.. haemoptysis. peritoneum. but. a t times streaked with blood. Yamagiwa . Masse s were observed in the abdomi nal wall and complicating abscess formation was seen28 . Migration of parasites through the peritoneal cavity was thought t o sometimes cause abdominal pain and tenderness.. however. 16 This was also appreciated in the same year by Manson who described his first patient.. I could discover no signs of lung disease on auscultation. sudden. and he says that the blood is always mixed with mucus after the first mouthful.Paragonimiasis 171 RECOGNITION OF THE CLINICAL FEATURES The major symptom of paragonimiasis. chest pain and night sweats were the most common symptoms. cysts were also observed in the liver . and of a bright red colour.120. the afflicted individuals were generally otherwise completely well: the disease manifests itself in that otherwise completely healthy individuals cough up blood-containing sputum for a long time. diaphragm. he says he has spat blood for two or three days at a time. the blood at first was pure. this second attack lasted for a few days only. profuse lung haemorrhage. were recognized gradually over the years in a small proportion of infected patients. in small quantities. Clinical manifestations of ectopic paragonim iasis. he first spat blood.. Kawamura and his colleagues late r claimed that Paragonimus infection may be a significant cause of centra l nervous system disease 46.. although eggs are sometimes seen only in the faeces. In many cases. so me of whom died.. there are epileptic attacks. he naturally turned his attention towards trying to cure them and made many attempts of dislodge the parasites. Wang and Hsieh showed that structural damage to the lung could be demonstrated b y chest radiography. In contrast. ectopic paragonimiasis has b een much more difficult to diagnose and this has depended upon finding either ova or worms in biopsy or autopsy material.172 A History of Human Helminthology subsequently concluded that the eggs that he had seen were really those o f Schistosoma japonicum. beginning with Ando in 1919 who showed tha t complement fixing antibodies were present in the sera of infected humans and dogs5. An intradermal test was introduced by Nunogami in 1930 95. The outstanding clinical features were described as follows: It begins with sudden severe headaches with vomiting and dizziness.. 11 cases of brain complications were found among the children. Microscopical examination of the sputum ha s remained the diagnostic method of choice since that time.47.. Various symptoms at the time of the onset disappear gradually. however.These attacks are repeated several times and may last from one to two hours or as long as ten or fifteen days. Spasmodic attempts have been mad e to develop immunoassays for the diagnosis of paragonimiasis. when sputum is swallowed 61.47 In other patients.. DEVELOPMENT OF DIAGNOSTIC METHODS Paragonimiasis is one of the helminthic infections in which the method o f diagnosis was established before the adult worm itself was defined. In one village of 686 inhabitants. he introduced a number . it disclose d Paragonimus eggs in caseous cysts in the brain. An autopsy was performed on only one of these children. the first such patient being reported in 1917 by Moriyasu 85. presumably. As des cribed earlier. although aetiological diagnosis was not possible 113. With consi derable ingenuity. THE SEARCH FOR EFFECTIVE TREATMENT When Manson found Paragonimus ova in the sputum of his patients. Ando and Yamada in 1916 were the first to report on the possibility of using chest radiography in the diagnosis of paragonimiasis 11. spastic paraplegia followed infection.. Nevertheless. In 1937. for tubercule bacilli 16 and Manson saw them in sputum whil e looking for microfilariae 69.mentality is weakened in some cases and in worst cases they become idiotic. Baelz found ova in the sputum of patients while he was looking. most commonly when it involved the lower thoracic area with extradural deposits of worms 98. Stibnal was said to be of value when tried in 19 patients by Kondo 62. and there were no parasitological relapses after a period of up to four months. four had no recurrence of symptoms. in experimentally infected dogs and thought that it brought about a rapid and radical cure 129. Of the nine patients so treated. Yokogawa and his collaborators used bithionol to treat 13 patients. Ikeda reported that he was able to cure three patients with 12-33 injections of emetine hydrochloride 39. santonin . Two new drugs have been shown recently to be highly effective. however. degenerating worm s which then became atrophic and calcificied. although its effectiveness in man y cases could hardly be called dramatic. Claims were made by many observers for the value of emetine. ergot and opium by Lara 63. Efficacy was claimed for pills containing a mixture of quinine. kousso. turpentine and sulphurous acid into the airways via a steam spray. seven could be followed up. In 1939. Katamine and his colleagues gave bithionol in various schedules to 22 patients. In 1975 . for example. sputum and stool specimens became negative in all patients 3-15 days after beginning treatment. that concurrent use of mercurochrom e shortened greatly the duration of emetine treatment 75.Paragonimiasis 173 of potentially parasiticidal agents. Martin. he believed. bithiniol was introduced and this became the drug of choice for nearly tw o decades. Haemoptysis ceased in four of the five patient s who had been troubled with that symptom. All o f them were cured after 5-15 doses given on alternate days. including quassia. In 1961. however. most of whom had bee n unsuccessfully treated previously with emetine and a sulphonamide. In control dogs which had been given emetine alone. S Yokogawa and Ro investigated the effect of combining emetine with the sulphonamide. eleven had transient side-effects. inst ancing one individual who needed 70 injections. Encouraging results with chloroquine were reported in 1954 by Chung and colleagues who treated three patients with paragonimiasis 29. Some patients required prolonged therapy to effect a cure. Kikuiko and Imamura described favourable results following the subcutaneous or intravenous inj ection of emetine daily for up to one week. A combination of emetine an d prontosil was therefore tried by Yokogawa and his colleagues in nine human patients with paragonimiasis. and the chest X-ray appearances improved in four persons 43. . Three years later. there was only a partial reduction in egg numbers an d little killing of adult worms in the lungs. When the largest dose was used. but noted that patients with longstanding disease were more prone to develo p untoward side-effects from the drug51. but the apparent effectiveness of thi s therapy was probably merely associated with periodical waxing and waning of the disease. one died of an unrelate d disease. the most frequent bei ng diarrhoea 124. and two relapsed with severe haemoptysis 131. but tartar emetic was not deemed to be very effective 75. but success did not attend his efforts71. Following in vitro experiments and animal trials. In 19 15. prontosil. Eggs disappeared from th e sputum and examination of the lungs disclosed dead. westermani 102. this agent seems destined to become the standard agent for the therapy of paragonimiasis. were important in transmission in some countries. westermani ova into the environment. were also found to be vectors of infection. other genera of crabs. Similarly. Cambaroides and Procambarus. the specimen being shown in the Japanese veterinary exhibit at the Paris exposition and bein g named by him "Metagonimus pulmonalis . depending upon the dose of prazi quantel used103. It became appreciated tha t different species of both primary and secondary intermediate hosts ha d different habitats. This was followed by the demonstration by various investigators that in addition to Potamon and Eriocheir. The dietary habits and methods of preparing crustaceans var y . whereas others inhabited delta regions. In 1892. UNDERSTANDING THE EPIDEMIOLOGY As the mode of transmission between first and second intermediate hosts was clarified and as the various reservoir hosts of the adult worms were identified. westermani was followed by the discovery that species of Brotia were also susceptible to infection. Furthermore. the cr ayfish. the epidemiology of paragonimiasis gradually began to be understood. Ripert and colleagues then examined the efficacy of a single dose of niclofolan in Cameroon and obtained a cure rate of 100% 105. praziquantel (see chapter 3) has been shown to be highly effective. Transmission of infection. ringeri. In the following year. however. and the shrimp. cysts have to be ingested in a viable state. westermani in dogs. pigs. panthers. Finally. westermanni". including Potamiscus. some living in mountain streams. In addition t o humans and the tigers originally shown to be infected by Kerbert. a wide range of vertebrates. For humans to acquire infection. however. Janson reported that Tokishige found the lung fluke in dogs and pigs in Japan. or better still. Thus. the realization that a snail. M. rathbuni) and then in P. depended upon the presence of definitive hosts excreting P. menichlopholan ( = niclofolan) was shown to give a cure rate of between 73% and 90% in humans infected with P. Melania (= Semisulcospira) libertina was the first intermediate host of P. Rim and co-workers in Korea reported that up to 100% effectiveness could be obtained. praziquantel had negligible side-effects. while the parasite was found in cats by Inouye and Katsurada in 1893 (cited in 128). Parathelphusa and Siamthelphusa. In 1981. wa s shown to be infected in nature 58. cats. including dogs. dehaani and Eriocheir japonicus by Nakagawa. however. Th e first advance was the discovery of infection in Potamon obtusipes (= P. Railliet in 1890 was apparently the firs t person to report the occurrence of P. Palaemon. or better M.59. wolves and foxes.174 A History of Human Helminthology Rim and his colleagues showed that niclofolan was effective in cats and dogs infected with P. uterobilateralis in Nigeria97. In contrast to niclofolan. 00 0 years118. while Koreans commonly eat fresh crabs as an antipyretic and an tidiarrhoeal remedy 57. the eating of crabs dates back at least 3. In China. as may have happened. Finally. In some areas. including Central America 63. THE EVOLUTION OF PREVENTIVE AND CONTROL MEASURES Even without knowing anything of the life cycle of P. even if desirable. infections are caused by species of Paragonimus other than P. control of molluscs is often not practicable. . Manson was able.Paragonimiasis 175 from place to place. with the Peruvian engineer who was a patient of Barton19. or eaten uncooked . by the use of elementary epidemiological principles. the crab juice is a domestic remedy for such ailments as whooping cough a nd measles 77. Extermination of crabs is next to impossible. although chemical agents and natural predators such as ducks and carp have been tried 7.or slightly-cooked. Sometimes the crabs ar e merely immersed in millet or rice wine. If these measures were adopted . infection may occur even without eating crabs as was indicated by the disease occurring in American soldiers who were presumed to have drun k contaminated water 106. health education campaigns have been carried out in several heavily endemic areas. with particular attention being paid to avoiding uncooked crabs and other potentially-infected crustaceans. to indicat e accurately the means by which human infection could be prevented: It is only necessary to boil or filter water. infection was recognized gradually amongst th e indigenous inhabitants of other regions. Central Africa65 and Melanesia35. westermani (see differentiation of species).71 The validity of these views was established when the life cycle wa s determined. westermani. Even though some of these infections may have been acquired as a result of transmission via immigrant carriers from endemic regions. paragonimiasis could be eliminated in human populations. but it is difficult to change the entrenched habits of a population. as happened in eastern Nigeria du ring the Nigerian Civil War of 1967-1970 96. South America19 . and never to eat uncooked vegetables or other uncooked food. it is now realized that in some of these foci. Similarly. owing to their hiding in deep holes and under stones in river beds57. Attempts to break the life cycle of Paragonimus by attacking one of the intermediate hosts are difficult. depending upon the preference of the consumer. The dish may be well. Famine may increase the consumption of crabs and thus precipitate an outbreak of paragonimiasis. so that these "drunken" crabs are still living when devoured. To this end. Although paragonimiasis has been found most commonly in eastern Asia. for example. kellicotti and P. westermani in the anatomy of the digestive tract 3. No doubt remained tha t paragonimiasis was endemic in the USA when Stiles and Hassal in 1900 recorded the discovery made two years earlier by AJ Payne of many lung flukes in pigs in Cincinatti. for when he examined flukes from a variety of both natural and experimental hosts in Korea. Ohio. As discussed earlier. westermani.176 A History of Human Helminthology DIFFERENTIATION OF SPECIES Speciation in the genus Paragonimus has long been a subject of confusion and controversy. and to this he gave the name. In 1894. they concluded that these flukes represented three separate specie s which they named P. Yokogawa was able to list 31 species of Paragonimus but recognized that some of them were not or may not be valid 122. P. At least nine species ar e believed cause to disease in man. P. westermani as two separate species. westermani. This seemed not unreasonable because it appeared until 1894. Ameel in 1934 reached the view that differentiation of species on the basis of cuticular spines was very doubtful. Ohio. Ward reached th e conclusion that the lung fluke found in cats. however. For a number of years. dogs and pigs in the United States was undoubtedly a distinct species. P. the lung flukes found in variou s animal species were also equated with P. westermani 107. but this view was no t generally accepted. these parasites were sent to Ward and he identified them as being identica l with those reported earlier by him from the cat 116. By 1975 . kellicotti 115. Exotic infection seemed less likely. however. Although differences were m entioned between this worm and those described by Kerbert in tigers and by Leuckart and others in humans. kellicotti and P. that all of these animals could hav e been infected in areas in which human paragonimiasis was endemic. he found great variation in the cuticular spines 56. although some of them may be synonymous. when Kellicott later that year discovered worms in the lungs of a dog in Columbus. Despite the difficulties in establishing the systematic position of new isolations. Henry Ward described a lung fluke obtained from a cat in Michigan. Kobayashi. especially as there was a possibility that the host had been brought as a pe t from the Orient114. Baelz classsified the human parasite no w known as P. a number of new species have been described in the last two decades. In 1908. th e parasite was nevertheless assigned tentatively to the species. ringeri. but found that there was a clearcut difference between P. this parasite also being given the tentativ e designation. USA. P. believed that there was but one species. On the basis of the structure and distribution of the cuticula r spines. respectively 117. westermani. . Ward and Hirsch compared Kerbert's original specimens from the tiger with animal material from the USA and human flukes fro m eastern Asia. on the other hand. In 1915. africanus eggs in sputa from 30 patients 112. The snail and crab intermediate hosts are probably Potadoma freethii and Sudanautes species. AFRICANUS This fluke was found in the mongoose and dog and was first described by Voelker and Vogel in 1965 in West Africa 111. respectively. cats and dogs infecte d experimentally32. It was described later in the same year as P. then in the lungs of 39 year old Laotian male 80. HUEITUNGENSIS Immature forms of this worm were first found in biopsy of migratory subcutaneous nodules from two children in China and colleagues in 1977 . P. tuanshanensis by Chung and colleagues30. Pomatiopis lapidaria and Cambarus are the first and second intermediate hosts. ecuadoriensis. respectively.Paragonimiasis 177 OTHER SPECIES OF PARAGONIMUS P. The crab host is Hypoloberca aequatoralis but the first intermediate host is as yet unknown. then the adult worms were recovered from rats. KELLICOTTI As discussed earlier. Tricula gregoriana and Potamon species were shown to be the first and second intermediate hosts. P. P. . ECUADORIENSIS This species was found in 1979 by Voelker and Arzube in a coati in Ecuador109. The snail host is Tricula cristata and the crab hosts are species of Siropotamon and Isalopotamon. respectively. It was first found i n humans in the subcutaneous tissues of the chest of a 13 year old boy i n Thailand by Miyazaki and Harinasuta in 1966 81. HETEROTREMUS This fluke was first reported in rats by Ch'en and Hsia in 1964 27. The same authors identified eggs in th e sputum of two patients in Ecuador as P. this worm was described as a separate species i n North America by Ward in 1908115. Later in the same year. Vogel and Crewe identified P. Human infection has been reported only once 2. P. nt Bulletin of the Museum of Comparative Zoology. 1910 . It commonly occurs in ectopic locations. respectively. 1948 2. P. then described more fully by the same author two years later 24 . respectively. Handbook of medically importa mollusks of the Orient and Western Pacific. P. SKRJABINI This worm was recovered from Paguma larvata (Viverridae) by Ch'en in 195923. Bythinella species41 and P. Harvard College 100: 245-328. ABBOTT RT. MEXICANUS This species was found in opossums in 1968 by Miyazaki and Ishii 83. The crab hosts are species of Sudanonautes. szechuanis by Chung and Tsao in 196233. Miyazaki and Ishii 83 also identified the eggs in the lungs of a 35 year old Mexican. and which had been described as P. P.178 A History of Human Helminthology P. Deutsches Archiv für klinische Medizin 100 : 501-511. Details of the life cycle were described by Brenes and collaborators in 1980 22. is generally considered to be a synonym. is now thought to be a synonym. westermani by Martinéz Báez and Jiménez Galán in 1961 76. Praziquantel was shown to be effective in treatment by Monson and colleagues in 1983 84. ABEND L. especially in subcutaneous nodules. UTEROBILATERALIS This trematode was recovered from a swamp mongoose in West Africa and described by Voelker and Vogel in 1965 111. A parasite recovered from cats. P. Ueber Haemoptysis parasitäria. as being those of P. Assiminea lutae 26 and Tricula gregoriana 31 are the first and second intermediate hosts. dehaani 108 were shown to be the first and second intermediat e hosts. REFERENCES 1. mexicanus. 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KOBAYASHI HARUJIRO. pp 55-62. China Imperial Maritime Customs. 1926 60. 1921 58. Leipzig. KONDO K. pp 3. 1915. MANSON-BAHR P. 1881 70. (Antimony treatment of paragonimiasis. A "critical review". Revision of the specific name of a crab as a second intermediate host ofParagonimus westermani in Formosa. 1919. 1925 & 1930. Reprinted in Medical Times and Gazette ii: 42-45. Mittheilungen aus der medizinischen Fachschule zu Keijo 2: 97-115. C F Winter'sche Verlagshandlung. West African Medical Journal 5: 51-52. Human pulmonary distomiasis caused by Paragonimus westermanni. 1918 92. 1923. with the same title. In Japanese. MIYAZAKI I. Japanese Journal of Parasitology 18: 123-130. 1907 87. The first case of human paragonimiasis caused b y Paragonimus heterotremus Chen et Hsia.) Taiwan Igakukai Zasshi No. Philippine Journal of Science B 2: 15-63. Sai Kin Gaku Zasshi No. KOENIG JW. (A contribution to the knowledge and development of the lung fluke). Journal of Experimental Medicine 26: 297-323. (Description of the cysts and young developing worms ofParagonimus westermanii. Lancet i: 32-33. 176. 1977 98. (On the migratory course of the lung fluke in the body of the final host). 1961 77. American Journal of Tropical Medicine and Hygiene 32: 371-375. NAKAGAWA K. The mode of infection i pulmonary distomiasis. Journal of Neurological Science 6: 125-140. NUNOGAMI M. 1969 83. Beitrag zur Kenntnis der Entwicklung für Paragonimus westermanii. Darmwand . In Japanese 95. MIRANDA H. MONSON MH. In Japanese 79. Abstracted in Tropical Diseases Bulletin 21: 539. Successful treatment with praziquantel of si x patients infected with the African lung fluke. 1968 84. Paragonimus peruvianus sp. SACHS R.) Tokyo Iji Shinshi Nos. OTANI S. (A preliminary report on the discovery of the intermediate host of th e human lung fluke. Certain freshwater crabs n as intermediate hosts of Paragonimus westermanii. of Kalapai as an intermediate host. In Japanese 96. NAKAGAWA K. Mature Paragonimus heterotremus found from a man in Laos. 1915. 1966 82. OH SJ. 281. 1916 90. Potamon dehaani. 1919 94. 1924 80. Abstracted in Tropical Diseases Bulletin 12: 174. ISHII Y. Hautgeschwülste durch Lungen distoma (Paragonimus westermani). In Japanese 93. Mittheilungen aus der medizinischen Fakultät der kaiserlichen Universität Kyushu Fukuoka 6 : 313-319. ONUIGBO WI. 1918. 1922. Paragonimus uterobilateralis. MINAMI S. Peritonäen. Spinal paragonimiasis. Tokyo Iji Shinshi No. American Journal of Tropical Medicine and Hygiene 26: 688-692.) Tokyo Igakkwai Zasshi 1: 458-460. Journal of Parasitology 6: 39-43. MIYAZAKI I. 1930 78.) Juzankai Zasshi 23: 1-2. SATO T. MIYAIRI K. NAKAGAWA K. Further notes on the studyof the human lung distome Paragonimus westermani. 1915. NWOKOLO C. MIYAZAKI I. with German summary. MIYAZAKI K. Paragonimiasis in the Philippine Islands. (Skin reaction in paragonimiasis. Zeitschrift für Tropenmedizin und Parasitologie 25: 433436. 282 and 283. IBANEZ N. Single dose therapy of paragonimiasis with meni chlopholan. 1883. 1972 97. Discovery of adult parasites of Paragonimus uterobilateralis in human tissue in Nigeria. NWAKO FA. NAKAHAMA T. Japanese Journal o f Parasitology 17: 445-453. 1983 85. Also. 1919. Journal of Infectious Diseases 18: 131-142. 254. Cited in 128 86. 1910. In Japanese 89. 1887. NWOKOLO C. Lymphdrüsen. Studies on the Mexican lung flukes with special reference to a description of Paragonimus mexicanus (Trematoda: Troglotrematidae). 1917 91. VOLKMER KJ. pp 366-368. Japanese Journal of Parasitology 19: 109-113. . On a new lung fluke found in Peru. 1974 100. (Ueber den Bau des Distomum pulmonis. Arbeiten aus der medicinischen Universität zu Okayama 2: 78-88.) Kumamoto Igakkwai Zasshi 6: 513. 1917. 1964. 1970 81. FONTAN R. Zeitschrift für medicinischen Gesellschaft . Annals of Tropical Medicine and Para sitology 60: 509-514.) In Japanese. NAKAGAWA K. n. HARINASUTA T. (Cysten des Gehirns mit Eiern von Distomen sonst in der Leber.) Tokyo Iji Shinshi No. NAKAGAWA K. Revista del Instituto de Salubridad y Enfermedades Tropicales 21: 101114. MORIYASU R. Outbreak of paragonimiasis in eastern Nigeria. In Japanese 88. 1930. 261. (Trematoda: Troglotrematidae). (A new species of lung fluke infesting the pond crabs. NAKAGAWA K.182 A History of Human Helminthology istrado en Mexico. 1968 99. (A case of myelitis caused by parasitism of Paragonimus westermani in the vertebral canal. InJapanese. MIYAIRI K. NAKAGAWA K. MUSGRAVE WE. RINGER BS. 1887 101. II. 1979 110. Yamaguchi Prefecture. Iranian Journal of Public Health 4: 42-51. 1915 118. WU K. Centralblatt für Bakteriologie und Parasitenkunde. VOGEL H. TOMIMURA T. HSIEH CK. . The epidemiology of paragonimiasis in China. Korean Journal of Parasitology 19: 27-37. Pulmonary paragonimiasis: a review with case reports from Korea and the Philippines. SUH WH. VOGEL H. CHIBA N. WARD HB. MORIBANI M. Archiv für pathologische s Anatomie und Physiologie und für klinische Medicin (R Virchow) 127: 446-456. iloktuensis. Annals of Tropical Medicine and Parasitology 9: 109-152. (Observations on the incidence of encysted larvae of Paragonimus miyazakii in Potamon dehaani in Rokuroshi. YAMAGIWA K. 1981 104. VOELKER J. Chinese Medical Journal 52: 829-842. Japanese Journal of Medical Science and Biology 5: 221-237. RIM HY. 1937 114. n. WARD HB. Data for the determination of human entozoa. Zeitschrift für Tropenmedizin und Parasitologie 16: 125-148. 1964. KUTSUMI H. The species of Paragonimus and their differentiation. SUZUKI S. LUDWICK RW. Zeitschrift für Tropenmedizin und Parasitologie 24: 323-328 . The lung fluke (Paragonimus westermanii) in swine and its relation to parasitic haemoptysis in Man. ARAKI K. BELL JC. Bilevon) on the animals infected withParagonimus westermani or P. on the methods of immuno-serodiagnosis for paragonimiasis .Paragonimiasis 183 Tokyo 1: 8-9. WARD HB. Distoma pulmonale. BAECHERE R. 1965 112. Clinical evaluation of praziquantel (Embay 8440. KIMURA K. YOKOGAWA M. 1973 111. VOELKER J. WANG SH. TAKEYAMA K. 1981 106. RIPERT C. Ueber das Vorkommen von Distoma westermanii in den Vereinigten Staaten. MINAI M. 1938 119. 1890 120. Roentgenologic study ofparagonimiasis of lungs. 1975 123. Human paragonimiasis in Eastern Nigeria caused byParagonimus uterobilateralis. (Paragonimidae: Trematoda). CHANG DS. KUM NP. Paragonimus and paragonimiasis. 1908 116. Ein neuer Lungenegel aus der Küstenkordillere von Ecuador: Paragonimus ecuadoriensis sp. Ueber die Lungen-di tomen-Krankheit in Japan. SAITO K. Iwakuni City. Japan . Archiv für pathologische Anatomie und Physiologie und für klinische Medicin (R Virchow) 119: 447-460 . Lancet ii: 1789. Studies on the biological aspects of the larval stages ofParagonimus westermanii. Korean Journal of Parasitology 14: 140-146. HA JH.especially. especially the invasion of the second intermediate hosts. Tropenmedizin un d Parasitologie 30: 249-263. 1900 108. CARRIE J. NWOKOLO C. Experimental chemotherapeutic effects of niclofolan (Bayer 9015. 1952 122. Comptes-Rendus Dixième Congrès. SAME EKOBO A. Paragonimus miyazakii infections in man first found in Kanto District. CREWE W Beobachtungenüber die Lungenegel-Infektion in Kamerun (Westafrika) Zeitschrift für Tropenmedizin und Parasitologie 16: 125-148. 1976 103. LEE JS. KIM S. Hanoi 2: 689-713. HIRSCH EF. with English summary 109. Beitrag zur Aetiologie der Jacksonischen Epilepsi. HASSALL A. WARD HB. 1953 107. Biltricide [R]) in the treatment of Paragonimus westermani. ARZUBE RM. 1965 113. RIM HJ. Annals of Internal Medicine 38: 1206-1221. Abteilung originale 15: 362-364. LYU KS. 1892 121. ROQUE FT. TSUJI M. Far Eastern Association of Tropical Medicine. MOMOSE T. JOO KH. AMBROISE-THOMAS P. PAUL ME. 501-515. Annual Report of the Bureau of Animal Industry 16:560-611. Zwei neue Paragonimus-Arten aus West-Afrika:Paragonimus africanus und Paragonimus uterobilateralis (Troglotrematidae: Trematoda). In Japanese.)Japanese Journal of Parasitology 13: 204-214. Résultats du traitement par le niclofolan. YOKOGAWA M. STILES CW. 1896 102. YOKOGAWA M. Transactions of the American Microscopical Society 28: 177-202. Cited in 69 105. YAMAGIWA K. 1894 115. VOELKER J. Étude épidemiologique et clinique de la paragonimose au Cameroun. TERAUCHI J. Bulletin de la Société de Pathologie Exotique 74: 319-331. Cited in 117 117. YOKOGAWA S. OKURA T.) Taiwan Igakukai Zasshi No. SANO M. In Japanese. 1922. RO M. Journal e of Parasitology 2: 111-118. 175. Acta Japonica Medica Tropica 1: 1-18. (C ercariae in Semisulcospira libertina collected from the endemic area of paragonimiasis. YOKOGAWA S. (Paragonimus ringeri.) Taiwan Igakkai Zasshi No. westermani Kerbert. (On the route of migration of Paragonimus westermani in the definitive host. YOKOGAWA M. Some notes on the encyst d larva of the lung distome. WAKISAKA K. WAKESHIMA T. Studies on the treatment of paragonimiasis. YOKOGAWA S. YOKOGAWA S. Formosa. 1960 129. Studies on the treatment of paragonimiasis. YOSHIDA S. In Japanese 133. On the intermediate hosts of th lung distome. P. (On the intermediate host of the lung fluke in Tokushima Prefecture. In Japanese 126. Abstracted in Tropical Diseases Bulletin 12: 173-174. Study of stages from the crab and points of difference distinguishing it from similar cysts occurring there. Translated in 48 127.) Tokyo Iji Shinshi No. 1915. 139-205. 1961 125. YOKOGAWA S. II. pp 685-700. YOSHIMURA H. 1934.) Taiwan Igakkwa i Zasshi 33: 875-876. pp 298-307. Japanese Journal of Parasitology 10: 317-327. 1916 . 1936. YOKOGAWA S. Acta Japonica Medica Tropica 2: 23-54. 1939 130. YOKOGAWA M. IWASAKI M . Shinchuku Province. Part I. Part II.184 A History of Human Helminthology Japanese Journal of Parasitology 23: 167-179. YOSHIDA S.) Tokyo Iji Shinshi Nos. In Japanese 131. (On the migratory course of the lung fluke in the body of the final host. Year 1915. Experimental Parasitology 10: 81-137. 152. 1934. 1916 134. Clinical observations on the treatment with bithiniol. Chemotherapy of paragonimiasis with bithionol. Journal of Parasitology e 2: 175-180. 1974 124. CORT WW. On the efficacy of prontosil in combination with emetine against lung flukes durin g treatment. Experimental treatment and efficacy on dogs harbouring lung flukes ( Paragonimus westermanii). 1940 132. YOSHIDA S. HIROSE H. 1915. 1920. Paragonimus and paragonimiasis. 1917. YOKOGAWA S. In Japanese. 1918 128. TSUJI M. SO K. Kobayashi. Landmarks in paragonimiasis __________________________________________________________________ 1877 1879 1880 Kerbert discovered adult worms in the lungs of a tiger and named the parasite Distoma westermanni Ringer discovered an adult worm in the lung of a human Baelz and Manson discovered independently eggs in the sputum of humans and recognized that haemoptysis was the main symptom with the patients being otherwise usually well Manson observed that eggs needed to incubate for several weeks before miracidia were released Manson postulated that a snail may be the first intermediate host and Hungerford suggested that Melania libertina was a likely candidate Otani found parasites in the brain Nakagawa showed that miracidia were not infective to dogs Nakagawa found encysted larvae which resembled adult Paragonimus in the gills of a crab which could be a second intermediate host Nakagawa reported that adult worms developed in dogs fed these cysts Ando. Yokogawa.1. Miyairi and Ando all concluded independently that snails of the genus Melania (= Semisulcospira) were probably the first intermediate host Yokogawa proposed a combination of emetine and prontosil for treatment Bithiniol was shown to be an effective treatment P. uterobilateralis infections were identified in humans by Onuigbo and Nwako Niclofolan was shown in experimental animals to be an effective treatment Rim and colleagues showed that praziquantel was a very effective drug 1880 1881 1887 1913 1914 1915 1915 1916-22 1939 1961 1965 1974 1975 1981 ___________________________________________________________________ . Kobayashi. africanus infections were identified in humans by Vogel and Crewe P.Paragonimiasis 185 Table 7. Nakagawa and Yokogawa determined independently the pathway of migration of larvae in the definitive host Nakagawa. . some of which are transported through the bladder wall and are passed in the urine. He found a worm. 12 mm in length by 1 mm in breadth. especially intestinal nematodes. Egypt in 1850. swim about in water. And so it did. 20x1 mm in size. the ova soon hatch miracidia which invade snail intermediate hosts of the genus Bulinus (Ferrisea and Planorbarius in small foci in Portugal and India. as to which branch o f natural science he should particularly direct his attention. he made a discovery that astounded him. and produce eggs. chimpanzees) Major clinical features: haematuria. especially in the vesical plexus. carries a slender female worm. as it seemed likely that the "strange country" would provide a fruitfu l field for such investigations. lose their tails to become schistosomula. praziquantel DISCOVERY OF THE ADULT WORMS Before Theodor Bilharz went to Cairo. which not only had he never seen before. then cercariae. Carl von Siebold. In early 1851. obstructive uropathy and secondary bacterial infections in heavy infections Diagnosis: demonstration of eggs in the urine Treatment: hycanthone. (Portugal. he sought the advice of his erstwhile teacher and mentor. The cercariae emerge from the snail. Bilharz was astonished at the variety and numbers of worms . then migrate through the bloodstream via the lungs to the portal venous system where they mature over three months Definitive hosts: humans (monkeys. causes vesical or urinary schistosomiasis or bilharziasis Major synonyms: Distoma haematobia. The male worm. baboons. Each miracidium becomes a sporocyst which in the course of 6-8 weeks produces second generation sporocysts. India) Life cycle: The adult worms are unisexual.Chapter 8 Schistosoma haematobium and SCHISTOSOMIASIS HAEMATOBIA SYNOPSIS Common name: vesical blood fluke. metrifonate. The adult worms live in the portal venous system. Bilharzia haematobia Distribution: Africa. but whic h 187 . niridazole. in its gynaecophoric canal. whil e carrying out an autopsy on a young man. then penetrate the skin of persons immersed in that water. Middle East. that he encountered during the course o f performing some 200 post-mortem examinations. respectively). Von Siebol d recommended that he concentrate on h uman helminths. On dilution in water. he wrote a letter. or haematozoon as he called it. as I had expected. I found in the blood of the portal vein a number of long. he explained how he had made this observation: I have not yet reported to you the new stages of my portal vein worm. He discovered that these helminths were unisexual and that he had been looking at the male worms. but soon recognized as something new. before he was able to shed some light on tha t question himself. Instead of the groove-shaped tail. I soon found specimens of the worm which harboured a gray thread in the groove of their tail. to von Siebold in Breslau. he named the worm Distomum haematobium. Furthermore. It did not. then published Bilharz's letters . including coining of the term "gynaecophoric canal" to denote the rolled ventral surface of the male worm which surrounded the filiform female worm. In some excitement. A look into the microscope revealed a splendid Distomum with a flat body and a spiral tail at least ten times as long as the body. but at first was misled by his initial failure to realize that the specimens that he was examining were all male worms. Bilharz's confusion is not at all surprising since all species of flukes known at that time wer e hermaphroditic. When I searched the intestinal veins more carefully (and more expediently by holding the undamaged mesentery against the light). histologically and morphologically.. white helminths which.. was a trematode. V on Siebold announced Bilharz's discoveries to the Congress of Naturalists in Gotham.. recounting hi s discovery: Soon after my attention had been directed to the liver and its associated structures.. the specific name presumably derived from a combination of the Greek words µ (HAIMA. 32 He concluded his description by asking the question: What then is this animal? In spite of its long tail. In another letter to von Siebold dated 28 August 1851.(HAIMAT-)] meaning "blood" and (BIOS) meaning "life. with the naked eye. the forked blind end of the intestinal canal extended into it very plainly.188 A History of Human Helminthology was located in the blood vessels. only much finer and more delicate. which is completely different. develop into a wonderful old wives' tale but into something more wonderful. Germany (now Wroclaw. The worm I described in my last letter was a male. a trematode with divided sex. ... to indicate that these worms lived in the bloodstream. He appreciated that this blood-dwelling worm. a location hitherto unrecognized in humans. You can imagine my surprise when I saw a trematode protruding from the frontal opening of the groove and moving back and forth. 32 It was not long. HAEMA) [combini ng form µ .was a continuation of the flat body of the worm itself.. In a third letter to von Siebold in December 1851 he enclosed preserve d specimens of the parasites and provided illustrations and a definitiv e description. The female was easily pulled out of the male's groove and was recognized most clearly by its internal structure. Poland).I found no mature sexual organs. similar to a sword in a scabbard. it had a ribbonlike posterior end which was completely enclosed in the groove-shaped half canal of the male posterior. dated 1 May 1851. it probably cannot be called a cercaria.32 He then went on to describe the anatomy of both male and female worms. I considered to be nematodes.. it was similar in shape as the first. however. rolled sideways towards the stomach surface in a half canal..the tail. course or way of living". of a South African colleague. he was able to demonstrate the characteristi c eggs. Furthermore. This latter term was derived from the Greek words (SCHISTOS) meaning "split" an d µ (SOMA) meaning "body". Harley found eggs of a worm. During the period between Cobbold's discovery of the worm and the formal publication of his finding.the extraordinary unisexual character of these flukes required thei r separation from the genus Distoma. Harley recognized the close . Harley secured urine specimens from the tw o sons. naming the worm Bilharzia magna. assistant physician to King's College and the London Fever Hospital. Cobbold at the time believed it was a new species and on 20 January 1859 presented his findings to th e Linnean Society. Thus. to indicate the characteristic gynaecophoric canal71. All of these authorities were agreed on one thing. Diesing communicated to the Vienna Academy his Revision der Myzelminthen in which he placed the fluke in a new genus. Weinland had used the name Schistosoma to describe this parasite in a list of all the worms that had thus far been found in man 202. Moquin-Tandon proposed the name Thecosema for the genus. in 1858. He was eventually to agree with Leuckart that the fluke found in the monkey and that described by Bilharz were identical and that bo th worms should thus be termed Bilharzia haematobia. but the names Schistosoma and Bilharzia both continued to be used for many years. to encompass these distinctive distomes. a resident of the Cape of Good Hope. in both instances. to denote its large size 54. South Africa . concerning the slight haematuria with which he had been afflicted for many years. since Saint-Hilaire had used the nam e Schistosoma previously to describe a particular form of monster 164. Dr Dunsterville. Gynaecophorus. Reinhard an d Lautner. In October 1863. Subsequently. however. T Spencer Cobbold found a similar bisexual fluke in the portal vein of a sooty monkey (Cercopithecus fuliginosus ) which had died in the Zoological Society's menagerie in Lon don. . CONTROVERSIES OVER NOMENCLATURE On 4 December 1857.Schistosomiasis haematobia 189 together with his own annotations. Moquin-Tandon's suggestion never met with any acceptance. named in honour of Bilharz. Even earlier. who had also suffered from haematuria. In all of these specimens. all of whom found worms in the portal veins and its tributaries in the mesentery and bladder. he erected a new genus. consulted by mail John Harley. and gave it the specific epithet. He also noted that many people in certain parts of the Cape were affected similarly and sent a number of samples of his urine to Harley. Both Cobbold's and Diesing's designations were ultimately to laps e because of the law of priority in nomencla ture. Bilharz's discovery was soo n confirmed by a number of pathologists including Griesinger. magna. in Zeitschrift für wissenschaftlich e Zoologie which both he and Kölliker edited 32. One o f these eggs hatched to reveal a "minute. ciliated animalcula" 102. capense became synonymous with S. B.. With respect to Diesing's Gynaecophorus he wrote: but. that the name of Distomum capense should not stand 56. Weinland (dated September 6th. In the subsequent discussion. Cobbold does not seem to have been entirely accurate in his facts. remarking that 'the generic term Bilharzia has the preference'. for his nomenclature was no t presented publicly until after that of Diesing. but from a bare comparison with the figures. when it was subsequently found that the title Bilharzia had been proposed by myself some six months before Diesing communicated his paper to the Vienna Academy. for S. that with a terminal spine. haematobium ova do not posssess a lateral spine. which had the additional advantage of handing down the true discoverer's name to posterity. and presented his findings to a meeting of the Royal Medical and Chirurgical Society in London on 2 6 January 1864. On the other hand.57 In 1931. More vexed was the question of the name of the genus. after careful comparison with Griesinger's figures and description. Senn put forward Bilharzia von Hemsbach 1856 as the valid name . his assertions are not clear. but it is apparent that he was then troubled by the absence of a lateral spine in any of the ova that he had found: I have never had much doubt of the identity of the North and South African parasites. 102 Again. 1861) that able helminthologist willingly abandoned the claims of Schistosoma. as was clearly shown by Leiper when he demonstrated the life cycle of S. because. haematobium. haematobium many years later. he could not justly infer that they were actually so. the choice of several systematists and others fell upon my title. In all my own cases I can say positively that only one form of egg has existed. the one with a terminal and the other with a lateral spine. and my position with regard to the question is pretty much the same as it was seven years ago.104 In fact. however.. Thus. and Leuckart's review of them in his recently published work. Cobbold declared that there was no doubt that the eggs described by Harley were identical to those of Bilharzia haematobia. haematobium described by Bilharz and Griesinger in Egypt (see next section). in 1870.57 Laudable though the latter objective may have been. he could hardly refer the ciliated embryo he had described to Gynaecophorus haematobium. I have never seen any egg with even a tendency to the formation of a side spine. Concerning Weinland' s Schistosoma he wrote: In a letter which I received from Dr. the resemblances were so close and so many that it was probable that they were identical. and therefore.. still I can only deal with facts. Harley felt obliged to place them in a separate species which he named Distomum capense 102. viz. Harley's reported response to this is incomprehensible circumlocution: He had referred to it as a new species.190 A History of Human Helminthology similarity between these eggs and those of S. he was correct and Bilharz and Griesinger were mistaken.both Bilharz and Griesinger describe and figure two forms of eggs. as discussed in chapter 9. Cobbold ardently defended his name Bilharzia against both Gynaecophorus and Schistosoma 57. Since the eggs that he had found differed in certain respect s from those described by Bilharz. Gynaecophorus Diesing 1858 or Bilharzia Cobbold 1859 183. He found them again in the following year and put forward the hypothesis that they were capsules representing a further stage in the development. "th e eggs are oval and pointed at one end" 32. These were probably empty egg shells of S. now contracting spherically. In the following year. perhaps a kind of pupal covering to protect the embryos when newly emerged from the eggs. he found these same eggs in the bladder mucosa and observed that they contained activ e embryos which escaped from the egg shells: "Many of these eggs containe d mature. the valid names for the organism and the disease ar e Schistosoma and schistosomiasis. the International Commission on Zoological Nomenclature by Opinion 77 in 1922 placed Schistosoma on the Official List of Generi c Names 113. Bilharz reported that he had seen eggs in the oviduct and uterus of female worms. respectively. empty egg shells" 32..moved briskly in all directions. and note d their characteristic morphological features . but Bilharz did not recognize them as such. that name being adopted earlier than either Schistosoma Weinland 1858. He then went on to recount the manner in which these larvae escaped fro m their constraints: (the) embryos. mansoni (see chapter 9). Bilharz was uncertain as to the fate of the embryos. he speculated that the healin g process had prevented the embryos from making their normal egress. It was completely covered with rather long cilia which enabled it to swim around in the water with a lively. now stretching out.. Leiper also tried to beat off the term Schistosoma by again drawing attention to the use o f the word for nearly a century by teratologists to denote a fairly common type of monstrosity in domesticated animals 140. developed blister-like bulges on thei r surfaces. Since these bodies wer e found in patients with old. cylindrical cone-shaped form which was thicker anteriorly and more rounded posteriorly. approximately similar to those eggs in size" 32. Nevertheless.Schistosomiasis haematobia 191 of the genus. DISCOVERY OF THE EGG AND MIRACIDIUM In his second communication to vo n Siebold in August 1851. 32 He then examined the behaviour of these organisms and found that they swam around in the water for an hour or so. In the same year. with a proboscis-like protruberance anteriorly. and finally tearing the egg shell: in this process they stretch out to their full length and tear the shell with a strong sideways pull. Thus. healed dysentery.the terminal spine writing. and that they prematurely went through a phase of development that normally occurred .. he had noted calcified areas in the liver along with S. haematobium eggs: "strange bodies provided with spines. 32 Bilharz then described the appearances of the free embryos (now known a s miracidia): The organism that emerged had a long. rotating motion. then finally lost their motility and dis integrated. In 1851. actively motile embryos: next to them lay broken. assumed a mulberry shape. 100 Little did Griesinger realise that more than 60 years of confusion. Monostomum mutabile. proper to the localities from whence the adult forms have been obtained. This is more understandable in the case o f Griesinger. a parasite of geese. however. it must be admitted that 30 years were to p ass before Thomas and Leuckart elucidated the life cycle of Fasciola hepatica. will be found in certain gasteropod molluscs. Cobbold57. and that schistosomes were very unusual flukes in that they were unisexual. or that von Siebold did not make this suggestion in hi s correspondence with Bilharz. First. and he must surely have known of Steenstrup's theory of th e "Alternation of Generations" (see chapter 4). He was an experienced and widely read helminthologist. He believed that patient investigation ough t eventually to disclose eggs. Griesinger speculated on the ways in which infection might be acquired. I would wish to discover the ways in which these entozoa penetrate the body. and the half-rotten fish that were beloved by the fellaheen. his major interests lay in the field of psychiatry. and it was for that reason that he was about to return to Germany. haematobium miracidia. I would have set myself two large practical tasks.55 . a number of investigators including Harley 104. but with considerabl e disingenuousness. however. This is relatively easy considering the simple food of the people. for although he made major contributions to parasitology . concoction and controversy would have to pass before light dawned on this problem. rediae and sporocysts. Spencer Cobbold in London. and in his textbook of 1864 on the human entozoa. was a pupil of von Siebold's and knew of th e latter's work on the relationship between miracidia of the trematode . Bilharz. It is perhaps surprising that neither Bilharz nor Griesinger appear to have paid any serious attention to the possibility that infection might be transmitted by snails. In their defence. thought that the problem should not present too muc h difficulty: Had I remained longer in Egypt. Since he was about to leave Egypt. Brock37 and Looss141 studied the anatomy and behaviour of S. He pointed a finger of suspicion at three main potential culprits: impure Nil e water. Following Bilharz. larvae or mature worms in one or other of these vehicles. particularly schistosomiasis and hookworm disease. however. THEORIES ON THE MODE OF TRANSMISSION Soon after the discovery of schistosomes. and certain cercaria-sacs found in snails. Sonsino186.192 A History of Human Helminthology outside the human body. that many authorities in the early 1850's did not accept a connection between cercariae an d distomes. he wrote that: it is more probable that the larvae in the form of cercariae. was on the right track. contaminated bread or grain and/or dates. he was unable to investigate the question himself. that he had undertake n some experiments in order to trace the development of the worm i n invertebrate intermediate hosts. are by no means conclusive. the direct infection experiment of Harley's and the search for a molluscan intermediate host by Harley and Cobbold. had indicated to a meeting of th e British Medical Association meeting in Liverpool. did they seem inclined to take up their residence. three and six months after infection. or by drinking unfiltered water into which the larvae had escaped. together with the outcome of his attempts to infect various species o f fish. since the conditions under which the experiments were made departed in several respects from those that are presumably essential to success in the ordinary course of Nature. and other fresh-water molluscs. Unfortunately. 57 These two approaches. Three animals were killed. What these forms are. entomostraca. Meanwhile. Cobbold in the same year. formed the basis for subsequent attempts to elucidate the life cycle of schistosomes . Nevertheless.57 However.and the adult sexual animal there are probably two distinct forms which serve to complete the chain of metamorphosis connecting these two extremes of development. Cobbold quite rightly qualified his findings by indicating that h e may not have reproduced the conditions obtaining in endemic areas: These experiments. He used ova obtained from patients infected in South Africa and: tried to induce the ciliated embryos to enter into the bodies of a great variety of animals. limnei. in his usual dogmatic way. He then examined this possibility in 1870 by attempting to infect experimental animals directly. Swimming freely about. and what are their transmigrations. are questions which require careful elucidation.. however. the debate on this subject ofte n sank into the depths of acrimony and vituperativeness. Cobbold. The results of these studies were published in 1872. but neither in them nor in sticklebacks. paludinae. or carp. haematobium eggs to two rabbits and two dogs in their food. He fed large numbers of S. dipterous larvae. different species of Planorbis. such as gammari.. capense. roach. one each at two... These views were echoed in the same year by Harley who wrote that: it may safely be assumed that between the ciliated embryo.102 Harley later put this idea to the test by examining some fresh-water molluscs (Unio kaffre) sent to him by Dr Dunsterville from an endemic area in South Africa but failed to detect any schistosomes 103.Schistosomiasis haematobia 193 Cobbold thought that human infection was probably acquired either b y swallowing the snails themselves. Having criticized him for his erection of B. began this with an attack on Harley in 1872. The ciliated embryo is adapted for an aquatic existence. these minute organisms probably come in contact with certain molluscs and become developed within them into what have been called cercaria sacs.Dr John Harley could possibly expect to rear Bilharzia by .. but no trace of schistosomes could be found 104.. he also kept his options open for as well he canvassed the possibility that the parasite migh t develop directly from ova introduced into the human body. gudgeon. Cobbold remarked that he doubted whether Harley had looked carefully into the writings of other investigators and then wrote: On what grounds. that direct infection should be proven or disproven by experiment. I have never met with a case in boys who do not frequently bathe in the Zwarlkojss or Booker's River. attention was focused again on water as the vehicle of infection when a dozen staff of the Eastern Telegraph Company at Suez were attacked . as early as 1864. van Beneden and especially Filippi. the teachings of Leuckart. if at all.and I confess to have the greatest difficulty in comprehending the purport of many passages .194 A History of Human Helminthology feeding dogs and rabbits with ova. I am at a loss to understand. as Cobbold himself had remarked in justifying separate generic status for Bilharzia. those few boys in the families of my patients who are free from the disease.Females are rarely affected. In 1882. .. Cobbold declared that it was quite clear to him that people in Africa were infecte d when they drank unfiltered waters 56. perhaps by being injected by the ovipositor of a minute. So far as Dr Harley is concerned in this particular relation. It was not only reasonable. Throughout the whole of Dr Harley's remarks on this head . My impression is that the parasite gains entrance into the skin while the individual is bathing in the river and I may mention that the lad W. and therefore to that extent utterly ignored. Harley quoted Rubidge in his second communication on the subject to the Royal Medical and Chirurgical Society: Pretty extensive enquires lead me to believe that bathing in rivers has something to do with the production of the disease. On the other hand. Guido Wagner. South Africa. Ther e were. As already intimated. Jones . Dr Rubidge of Port Elizabeth. described a sort of urticarious eruption attended with great irritation. 179 Following on from this.57 This was an unjust criticism for Harley had in fact been much more scientific in his approach than the cocksure Cobbold. and had actually looked for schistosomes in snails before Cobbold had.. bathe in the sea only. put forward a novel ide a based upon perspicacious epidemiological and clinical observations when he wrote to Harley in London in response to the latter's request for information on endemic haematuria. are altogether a dead letter. two views as to the way in which infection was acquired from water. had suggested on general grounds than an intermediate hos t might be necessary. As early as 1864. Permeating both the "direct" and "snai l" theories was the widely held belief that water was intimately concerned in the transmission of infection.the generally received opinion as to the necessity of an intermediate host amongst the Trematoda seems to me to have been altogether overlooked. leech-like animal 104. Siebold. I have not myself observed a single wellmarked case in this sex. as a frequent result of bathing in Booker's River. But he realized. is to me a mere haphazard conception. and one which virtually sets at nought the well established experiences of every original experimenter whose name is known in connexion with the advancement of helminthology in its ontogenic bearings. that schistosomes were so different from other flukes that it did not necessarily follow that were transmitted in the same way. Pagenstecher. and his apparent suspicion that parasites 'may increase in the (human) body from the development of eggs' in a direct manner. but necessary. however. Harley.. Harley in 1870 put forward the hypothesis that ov a may be inserted into the skin while bathing. Two years later. remain free of the disease. Allen was supported by Lyle. so that granting the larvae to have the power of penetrating the body by some means. that the symptoms earliest make their appearance. It is not so often in girls. In fact. soon imbibe it. there was a separate supply of unfiltered water direct from the Nile fo r gardens. 101 Allen later (1888) came around to this notion. was possibly a consequence of faulty storage of water." 38 and that females were rarely affected. even in those who did not bathe in the Nile. who are fondest of swimming. is extremely obscure. or was a result of the consumption of raw vegetables or fruit that had been washed in dirty canals or rivers 73. She concluded that infection was unlikely to be due to bathing. Guillemard (1883) was not so sure that drinking infected water was the correct explanation. while the girls. She found that i nfection was common in young girls. living much in the veldt and drinking copiously from the first stream they come across. He referred to Sonsino's patients in th e Zagazig where not a single female case occurred. and suggested that it was via this route that the girls acquired thei r infection137. who do not bathe. is in some way connected with the acquirement of disease seems the most tenable. disconnected. 6 and suggested that an unknown larval stage might enter the body through the skin. al so of Natal 150. After stating that "it i s among boys. In 1894. in addition to piped filtered water for drinking. which is but seldom indulged in by women.4 In this view. contradictory" 145. the infection was most common in natives and in the mal e children of white settlers. they are the largest consumers of unfiltered water. than from the comparatively small amount conveyed into the stomach by drinking. we should expect to meet with a much larger proportion of cases among bathers than among those who only drink the infective water. South Africa. the chances of infection occurring will be greater from the large quantity of water which must come in contact with the body in bathing. but was rare in adult women.Schistosomiasis haematobia 195 with schistosomiasis after drinking water from the Sweet Water Canal while walking or shooting nearby12. he remarked that: other things being equal. but the supposition that river-bathing. Allen also noted that in Natal. In the same year. they staying at home more can as a rule get filtered water. 38 In contrast. then put forward the following observation: The reason is very evident. so far from being evident. He favoured the possibility that infection occurred while bathing in contaminated water: The mode of infection. boys and natives. Elgood and Cherry later disputed the significance of Leiper' s . and Castle in East Africa 40. Looss acidly replied that Dr Elgood's conclusions "appear deficient in lucidity . While agreeing that infection was much mor e common in males. remarking that: Nearly all the youths bathing in the Umdimdusi and Drop Spruit are infected. Leiper was later to show that Cairo had two water supplies. yet only unfiltered water was available. Sonsino in Egypt 188. Brock supported this view strongly. Bronte Elgood (1908) examined the relationship between the prevalence of schistosomiasis and water contact in schoolgirls and in female hospital patients in Cairo. for he considered it impossible that miracidia could live under the conditions suggested. 196 A History of Human Helminthology observation. Finally. The first major contribution came from Sonsino in Egypt in 1884187. a doctor who had practised in Africa. It has also been suggested tha t further evidence for such a belief is provided by the penile covers or condoms that are present on several ancient Egyptian statues and reliefs.ergo thei r schistosomes could not be acquired in that way. Egypt. and Leuckart's assistant. enforced circumcision as a contro l measure in every country where schistosomiasis was prevalent 8. as telling him that the indigenous inhabitants of Central Africa believed that the parasite (or at least the cause of th e haematuria) entered the body via the urethra. and if the distoma enters with it. but this idea was uniformly laughed out of court. attention turned to experimental investigation of the transmission of infection in endemic areas. Similarly. however. for exampl e remarking that "Apes and the like do not practise ablutions . it is obvious it would be guided almost immediately to the mouth of the urethra and sustained until it effected entry. Nearly ten years later. Leiper led a team to Egypt in 1915. haematobium ova. Manson. Following Harley's and Cobbold's negative but pioneering studies i n Britain. the idea was sanctioned in a leading article in The Lancet (1900) in which infection via the oral and urethral routes was compared: It is by no means improbable that the parasite may enter the body by both of these methods. three special missions visited North Africa between 1893 and 1894 in search of a solution: Sonsino. DIRECT INFECTION EXPERIMENTS Despite Harley's failure to infect rabbits and dogs with S.7 He then went on to advocate universal. then a lecturer in parasitology at the University of Pisa went to Tunisia. although haematuria would probably only follow invasion by the urinary route. As mentioned earlier. and neither could those o f man"154.16 This notion was espoused by Allen who wrote: There can be no doubt but that the prepuce plays a most important part in the entry of the parasite into the urethra. Lortet and Vialleton were sent by the French government to Egypt. Consequently. these studies fell into two broad groups. for they found vector snails in public ponds an d fountains and in private gardens in Cairo 74. they tied up the penile orifice before they crossed a river 163. went from the University of Leipzig to Alexandria. During the act of bathing the sac formed by the prepuce becomes filled with water. A novel but logical suggestion for the acquisition of urinar y schistosomiasis was publicized by Norman Moore at a meeting of th e Pathological Society of London in 1882. Looss. . it was also suggested that infection might be ac quired per anum while bathing 180. In any event. but he could not solve the problem. He quoted a patient of his. I have already made some trials for introducing larvae into the animals. they passed eggs into the stomach of guinea pig s through a tube. albeit h e accepted eventually that infection occurred through the skin. administering miracidia orally. rabbits. Bu t Looss remained obstinate. . they must travel through the skin as he had already shown was the case with hookworm larvae. Despite his failure to prove infection by this means. Wolff in German East Africa (1911) failed to infect a cat immersed for half an hour in water swarming wit h miracidia204. again the results were negative 142. lightly excoriated legs plunged in water containing many S. all wit h negative results61. explain ing all these failures with the claim that man was the only known host for S. The former tenet was held because he failed to find an infected intermediate host. Yet as Milton later justly remarked. as will b e detailed shortly. perforce. Conor carried out an extensive series of experiments in Tunis. and being conducted without system. haematobium miracidia for three months. Bour in Mauritius (1912) was unable to infect two cynomolgous monkeys. crassa miracidia instead 161. He regretted . Lortet even kept sheep with shaven. Looss explained the rea soning upon which the latter statement was based to the Egyptian Medical Congress in 1905. injected ova intravenously into rabbits. Finally.Schistosomiasis haematobia 197 this idea was not given up and was examined repeatedly by a number o f investigators. haematobium 147. His argument wa s centred principally upon his demonstration that miracidia could not survive in stomach juice or hydrochloric ac id. despite repeated attempts to confirm his thesis: Unfortunately I still cannot furnish you with the indisputible proof by experiment.143 Other investigators also kept trying. either orally or percutaneously 36. Fülleborn. fewer than the rest. haematobium eggs in urine mixed with milk 108. a parasite closely related to S. percutaneously an d subcutaneously to monkeys. did not give decisive results. but these experiments. sheep. guinea pigs and rats. He had chosen sheep as the host as many sheep in Sicily were infected naturally with Bilharzia crassa. Hatch in India failed to infect puppies by feeding the m with S. and fed Macacus monkeys with eggs in their food 149. however. Looss championed th e notion that transmission did not require an intermediary host. Leiper and some of Looss's ow n colleagues in unpublished studies 134 failed to achieve infection directly. Mantey made some experiments in 1880 but his results wer e negative157. while Joyeux in French Wes t Africa was unable to infect a Cercopithecus ruber monkey by bathing it in urine containing miracidia 117. In 1894. thi s experiment would have been more meaningful if Lortet had used B. haematobium. Looss gave various species of monkeys (since Cobbold had shown that they were susceptible to infection) water containing miracidia to drink repeatedly for six to eight weeks. but found no trace of adult worms at post-mortem examination 148. In 1914. In 1882. Also in 1894. that he did not have any proof. Lortet and Vialleton failed in all attempts to produce infection directly. He believed that he had discovered that a small crustacean was th e intermediate host. Limnea. however. haematobium by following the approach already taken by Cobbold. His studies were divided into two parts. he d id not publish his results but sent a sealed . Secondly. Physa. The Khedividial laboratory. Ten years after his arrival. and in part parasitic in a single definitive host.187 Sonsino's work was regarded highly. Thomas. Planorbis.A. he tried to infect experimentally snails kept in an aquarium .13 Six months later. Moreover. Sonsino returned to North Africa to recommence his studies into this question. H e concluded: It is probable that Bilharzia. he turned his attention to examining the life cycle of S. In this way. Sonsino concentrated on snails as being the most likely intermediate hosts. Eight years later in June 1893. differs from other genera of distomes and presents this peculiarity: that it possesses as intermediary host animals belonging to classes different from those which serve as carriers to other Distomidae.14 Nothing happened. a successful result might be brought about in one or two years. Unio and Vivipara were examined while searching for evidence of natural infection with schistosomes.. Physa and Vivipara were exposed to S. haematobium miracidia. this peculiarity invests to this end all its life-history. He went to Tunisia and found some patients who provided him w ith ova in sufficient numbers to allow him to rear miracidia in association with freshwater molluscs and arthropods. Perhaps stimulated by the successful determination of the life cycle of Fasciola hepatica by Thomas and by Leuckart in 1882. Melania.offers every facility.. Melania. with a special correspondent to th e British Medical Journal writing in December 1884: Dr Sonsino is continuing his researches. to select a man and set apart funds for research.into the life history of parasitic trematode worms. Species of Cleopatra. and there is good reason to hope that by working along the lines of Mr.198 A History of Human Helminthology THE SEARCH FOR AN INTERMEDIATE HOST The first major attempt to investigate transmission in an endemic area wa s made by Prospero Sonsino.. a further note appeared in the same journa l regretting Sonsino's departure for Italy.. owing to several other peculiarities. but infection failed to develop. it should be much easier to set this question at rest. After Mr. Firstly. local snails including species of Cleopatra. Mysteriously. an Italian physician who had been appointed i n 1873 to the Khedividial laboratories in Cairo and had access to Kasr-El-Aini Hospital where he was able to examine patients and perform autopsies. in part free in water. but again he met with no success..M. Corbicula. It would be worthwhile for the B. it is to be hoped that he will discover the intermediate host of Bilharzia haematobia. Thomas's successful search in the case of sheep-rot.. and surely through alternating generations. The correspondent then went o n optimistically: There is now a clear field for an investigator to find the intermediate host of Bilharzia haematobia. I repeated those of Cobbold and Sonsino. but with the like absolutely negative results.it was published in the Pisa Society's proceedings but not in The Lancet! Nevertheless. indicating that S. 189 Sonsino then amplified his conclusions. Melania. in a manner similar to that observed in other species of distoma. haematobium resembled a holostome rather than a digenetic trematode and underwen t metamorphosis but neither alternation nor asexual generation in a smal l crustacean. so he searched for natural infections amongst local molluscs: Naturally. In the event. He stated that the free-swimming miracidia penetrated th e crustacean at its head. haematobium 149. Physa. Sudan. then encysted. Looss in Egypt embarked upon the trail. It must be admitted though. Initially (1893). Simultaneously. he changed his mind and wrote to The Lancet. i n 1904 when he wondered whether the minute crustaceans (probabl y Ostracoda) obtained from a school well and which took up miracidia might not be the long sought for intermediate host 24. Lortet and Vialleton reported that they were unable to infect a number of species of molluscs (includin g Corbicula. but again without luck 148. Perhaps he was not sure of his facts. i ndicating the nature of his discovery and when he had made it. In my experiments in this connexion. This report was received with acclamation in an accompanying Lancet editorial15. he predicted that molluscs would be vectors. France with local species of Lymnaea. aquatic arthropods. the most likely course and that which one expected a priori was for the embryo after escaping from the egg-case to penetrate. like Cobbold and Sonsino. Nothing came of this suggestion either. Human infection was acquired b y ingesting these infected crustaceans in contaminated drinking water. that this withdrawal was less public than it might have been . but was afraid that Lortet and Vialleton would beat him to the mark. but in the following year further work indicated that these conclusions were completely untenable and forced Sonsino to withdraw them entirely 190. into some intermediate host appertaining to the class of mollusca. to the secretary of the Societa To scana di Scienze Naturali in Pisa. Unio and Vivipara). At around the same time as Sonsino (1894). his paper appearing on 9 Se ptember 1893. he proclaimed: After many experiments I succeeded with a small crustacean (amphypoda) and obtained evidence that this same crustacean is an effective intermediary host of bilharzia. This led him to state categorically in 1894: It is more particularly these latter negative experiences that induce me now . he failed to find any evidence of schistosomal infection. and so discovered the secret of the life history of the African parasite. or water plants with S. 142 Even when he dissected snails from the most notorious foci of human infection in the Nile delta. He then went on to say that his further researches had revealed that larvae of several kinds of aquatic insects were also efficient vectors. Lanistes. Sonsino's idea was adopted tentatively by Balfour in Khartoum. Lortet then continued thi s experimental work in Lyon. Without providing any details of the experiments.Schistosomiasis haematobia 199 letter dated 3 August 1893. haematobia. British authorities became concerned about the potential deleterious effects of schistosomiasis on British troops in Egypt. but failed to do so when they were immersed in water full of miracidia. 142 In like manner. One commentator remarked: Hitherto. At the outbreak of war in 1914.147 Nevertheless. ELUCIDATION OF THE MODE OF TRANSMISSION: DISCOVERY OF THE LARVAL STAGES AND THE SNAIL INTERMEDIAT E HOSTS. he failed to infect crustacea. 142 He reiterated this view in 1905 143 and again in 1908144 . and any attempt at upsetting the classical research of the great authority was considered to be well-nigh sacrosanct. tenaciously and immovably for the next 20 years or so: The above described behaviour of the embryos towards other animals was in the main what led me finally to the definite conviction that probably no transference of the embryos by means of an intermediate host appertaining to the classes of the lower animals takes place. the offspring of the cyst being subsequently distributed to its host. This concern was founded upon their e xperiences with schistosomal infections in British soldiers in South Africa during the Boer War. insect larvae. small worms an d fish. 1909145 and 1910146 . that the way was left open for Leiper to make his epocha l discoveries. Hence the only possible solution that remained was that the embryo reached man directly. Even after Japanese investigators succeeded in infecting a variety of animals with S. Loos s pontificated as late as 1914: It is remarkable that the Japanese authors do not appear to be able to come to any clear concept as to the nature of the invading form. Such was the authority and vociferousness of Looss. including Blanchard 35 and Manson 155 in their textbooks. however. in his annual report in 1913 in which h e emphasized that "It is high time that serious steps should be taken to prevent the continuity of infection that has been going . although it mus t be admitted that their views were based upon theoretical considerations rather th an personal. practical experience.200 A History of Human Helminthology definitely to exclude mollusca as the intermediate hosts of our parasite. the British administrator of Egypt. and develops into a sporocyst in the human host. for it seems a priori difficult to understand how an intermediate host that lives in water can participate in the spread of B. and had been given deeper expression by Lord Kitchener. there were dissenters. japonicum by immersing them in flooded fields in endemic areas. that his dogmati c statements effectively inhibited the search for an intermediate host for 2 0 years. Bilharzia japonica must differ essentially in its development from B. This led him to the conclusion which he maintained stolidly. the scientific world had listened to the teaching of Looss.17 It was not until Looss was banished from Egypt by the British at the outbreak of World War I. haematobia in the towns of Egypt. Lortet. in particular. japonicum and was familiar with the recent discoveries by Japanese workers. Furthermore. the team made discoveries of immense importance. only ten had bee n examined by the combined efforts of Sonsino. Finally. Robert Leiper had just returned from Eastern Asia where he and At kinson had been investigating the life cycle of S. Leiper and Drs RP Cockin and JG Thomson. Leiper himself was afflicted with scarle t fever and was admitted to hospital. The influx of the wounded from th e Gallipoli campaign in May brought pressure for closure of the study. Leiper continued his observations in England and again in Egypt on his subsequent return there in Novembe r 1915. Thei r findings were reported in three instalments in the Journal of the Royal Army Medical Corps. experimental animals were to be infected with them and the route of infection determined. Fourthly. Vialleton and Looss .Schistosomiasis haematobia 201 on so long in the country"129. if cercariae could be found in snails. snails were collected from ponds in the Botanical and Zoological Gardens at Giza. British authorities were receptive. he returned to England on 15 July 191 5 leaving behind Thomson who had joined the general service of the Roya l Army Medical Corps. a highly endemic area a few miles north of Cairo. his studies of S. Finally. Leipe r realized that it was imperative that he had expert pharmacological advice in the matter of testing anthelmintics. were given temporary commissions and sent to Egypt by the British War Office to "Investigate bilharzia disease in that country and advise as to th e preventive measures to be adopted in connection with the troops" 134. Leiper had his team set about the collec tion and identification of all the species of freshwater molluscs that they could find in the province of Qaliub. Within a month of their arrival. Leiper and his colleagues set up headquarters i n Looss's vacated laboratories in the Cairo School of Medicine. when experimentally infected animals were eventually obtained. then dissected them in order to look for any larvae which showed morphological characteristics of schistosomes. th e bionomics of the molluscan intermediate . The second phase of the plan was to ascertain if schistosome miracidia exhibited chemotactic behaviour towards any species of mollusc . the absence of a muscular pharynx 137. it was planned to assess the efficacy of variou s chemotherapeutic agents. therefore. Neverthel ess. haematobium from cercariae of the other distomes on morphologica l grounds. Thirdly. beginning in July 1915 134. who were to assist him. Leiper ha d reviewed the literature well and realized that of the 50 species of freshwater molluscs that had been described thus far in Egypt. and brought out two further pa rts of his report in 1916 135 and in 1918 137. during this brief period and working with incredible speed. Consequently. Cockin fell sick and had to be invalided home. By a stroke of irony. The mission arrived in Egypt on 8 February 1915 and was beset wit h difficulties almost from the start. Consequently. if all o f these were successful. including those of S. In addition. to Leiper's submission that he be allowed to study the problem of th e transmission of schistosomiasis in Egy pt. japonicum cercariae while in Japan ha d convinced him that he could distinguish s chistosome cercariae. haematobium of humans. Thus. Furthermore. ducks. Planorbis boissyi (now known as Biomphalaria alexandrina) and Pyrgophyla forskali were found to be chemotactic fo r miracidia hatched from schistosome ova. geese. while the third form was seen in P. 26 white rats. tuberculata. a lamb . chickens. Le iper wondered whether they represented the three species of Schistosoma that were supposed to occur in Egypt: S. was found in Planorbis mareoticus. a young rat which had been exposed on 4 May was found to be infected. four mice. S. The second type of cercaria was discovered in P. but since they had not reached maturity . they showed that each cercaria lost its bifid tail o n penetration of the skin of the final host. Altogether. boissyi or Bullinus. 15 species of molluscs wer e recovered from this site. On dissection of wild snails. in 1915. he was able to show that the incubation period of the infection was approximately 6-8 weeks. The first form of cercaria. Limnaea truncatula. which was the home of an Arab attendant in the Department o f Parasitology of the Cairo School of Medicine. All the experiments on birds were negative but on 13 June 1915. P. 16 desert rats. mice. Leiper infected with cercariae from P. boissyi and Melania tuberculata. crows and wagtails percutaneously. Cercariae from these snails were used to infect a calf. bovis of cattle and Bilharziella polonica of ducks. which was distinctive and which he thought wa s probably the avian form. rats. Schistosome worms were found in the liver and mesenteric veins. While in Egypt. Leiper used the monkeys t o compare the percutaneous and oral routes of infection. thre e forms of cercariae of the schistosome type were found in four species of snails from El Marg and the Gardens. Cercariae developed within these sporocysts. differentiation between S. were to be studied. Leiper and his associates also studied the development of larvae in susceptible species of snails and found that miracidia gave rise t o sporocysts which in turn produced daughter sporocysts that migrated into the digestive gland. but Leiper thought it most likely that the las t animal was infected by cercariae penetrating the oral mucous membrane. Leiper was in no doubt that certain species of snails were the required intermediate hosts of the worm or worms that caused huma n . bovis was difficult. and took them back with him to England .202 A History of Human Helminthology host. Examination of these animals when they arrived in England disclosed that all of them had enormous numbers of schistosomes with "characteristic eggs" in the portal system. if found. almost 30 species of snails from various locations were examined. Encouraged with this success. and thes e eventually ruptured releasing the cercariae which were then discharged int o the water. Four species. boissyi and M. Bullinus (now known as Bulinus) species. haematobium and S. Attention finally focused on a village called El Marg. two guinea pigs and four mangaby monkeys. nine miles north of Cairo. boissyi and a species of Bullinus. Further. as was on 24 June a mouse that had been infected on 2 May . Three monkeys were infected percutaneously and one was infected orally. All eventually died o f heavy schistosome infections. FG Cawston turned his attention to determining the mode of transmission of the terminalspined S. haematobium with the terminal-spined eggs was transmitted by snails known to Leiper a s Bullinus contortus. They recovered S. Director of the Natal Government Museum. Enough was known for a general understanding of th e epidemiology of the infections. moreover. howeve r. haematobium adults from monkeys infected experimentally with cercariae from Bulinus then infected Bulinus snails with S.Schistosomiasis haematobia 203 schistosomiasis. generally resembling those seen with S. but not in Limnea (= Lymnaea) natalensis exposed similarly. and to devise effective control measures . However. japonicum in the Orient. cercariae with bifid tails. and that S. it was still a matter of debate whether there were one or two species of schistosomes. were found encysted within the liver of one of th e snails identified as Physopsis africana (now known as Bulinus [Physopsis] africanus). which snails were the vectors of which species. Furthermore. Suffice it to say here. Oken in 1815 changed the name to Bullinus. contortus. which was believed to be the source of schistosomiasis in Pietermaritzburg. that th e upshot was that there were indeed two species. In 1927. that the nomenclature of B. dybowski and B. innesi. The studies which Leiper undertook in London and on his return trip to Egypt are detailed in chapter 9. The taxonomy of these snails was confused further when Ehrenberg in 183 0 erected the genus Isidora for certain Egyptian and Syrian forms. japonicum. It was not until 1931 whe n Baylis28 reiterated these points. Consequently. although Annandale considered that it was synonymous with Bulinus 10. and being stimulated by th e recent discoveries concerning the life cycle of S. and other scholars treated it as a subgenus of Bulinus. Dr Watkins-Pitchford. amongst other names. Pilsbury and Bequaert declared that Isidora. truncatus became accepted generally. Leiper's results were confirmed by Manson-Bahr and Fairley who studied schistosomiasis between 1916 and 1918 in Imperial troops of the Egyptia n Expeditionary Force. snails were taken from a swimming pool. innesi were all synonyms of each other and. Concurrently with Leiper's work in Egypt. Leiper and many of the other early investigators spelled the generic name of the snail intermediate host as Bullinus. Director of the South African Institute of Medica l . Annandale 10 pointed out that the genus was described originally from a West African specimen by Adamson in 1757 who spelled it with a single "l" even though the word was derived from "bulla". B. B. After three to four weeks. haematobium eggs. In collaboration with Dr E Warren. then mixed with urine containing S. since the latter specific designation had precedence. and if the latter was the case. haematobium miracidia and confirmed that Planorbis was resistant to these miracidia 156. Annandale in 1922 wrote that B. Many South African authors used this designation. was synonymous with Bulinus 173. the correct name for the snail was Bulinus contortus 11. that they were also synonymous with Physa truncata. haematobium in South Africa. dybowski and B. haematobium finally turned out (when sent to Leiper for identification) to be that of S. publishing these indeterminate findings in three different journals 41. Cawston finally had a modicum of luck when he succeeded eventually in infectin g laboratory-reared P. much to the exasperation of Leiper who wrote "There is no evidence that the various forms so loosely and repeatedly termed 'Bilharzia cercariae' in thi s author's numerous papers are actually such" 138 and "The subject matter ha s already been repeatedly reviewed in this Bulletin.136 A multitude of papers flowed from Cawston's pen over the next several years. He exposed a mouse and a guinea pig to washings obtained from infected snails. then recovered S. first communicated these results in July 1915 198. haematobium miracidia and obtained cercariae six weeks later 44. mansoni (occasionally). A focus of infection with S. Porter was later to remark that cercariae of at least 22 different species has been found in P. Several years later. africana42. haematobium ova. Blacklock an d Thompson in Sierra Leone also infected Physopsis with miracidia from S. 17 autochthonous cases of schistosomiasis were found i n Portugal. In Egypt. In 1920. one of these so-called cercaria of S. in this. haematobium. In the following year (1916). he was later proven to be correct 29. haematobium (commonly) and S. Annie Porter showed by infecting experimental animals that P.204 A History of Human Helminthology Research. obtained cercariae from these snails. africana was naturally-infected with both S. haematobium was found in a village nea r . africana with S. and the present pape r contains nothing new" 139. haematobium adult worms 33. Cawston the n indulged in what was to become a favourite hobby of his. even though Warren looked upon these observation s as merely tentative and deprecated the drawing of definite conclusions. haematobium174. The presence of a bifid tail is no indication that a cercaria belongs to any special systematic group.4% of 533 specimens of P. bovis43. and that Lymnaea natalensis rarely harboured cercariae of S. however. but the mouse escaped and schistosomes could not be found in the guinea pig at autopsy six months later. In 1921. Nevertheless. particularly as the snails could have bee n infected naturally and as there was no proof that they were the cercariae of S. Publication of Leiper's discoveries prompted a flurry of activity by Cawston. africana 175. he recorded finding "bilharzia forms of cercariae" in 17. haematobium and opined that Planorbis corneus var metidjensis (now known as Planorbarius metidjensis ) was likely to be the intermediate host 88. França investigated the attraction of various species of local snails for miracidia of S. Cawston had made a quite unwarranted assumption an d Leiper condemned this when reviewing the paper for the Tropical Diseases Bulletin: The use of the term 'Bilharzia forms' for cercariae with bifid tails is exceedingly misleading. In fact. 9 out of 27 recorded species of cercaria have 'bifid tails'. infected monkeys and guinea pigs. 30 Bilharz also noted that this worm may be related to disease of the large bowel and indicated that eggs had been found in dysenteric intestines.They were ecchymotic and often encrusted with urinary salts. then it was shown by Gadgil in 1963 that the local vector was the limpet. I.. Although he considered it likely that the pathological processes in the bladder and the gut were identical. we observed dark gray. This led him to ask: Is my ineptness to be blamed or is the worm attracted by the initiation of primary disease of the intestine or is the worm the direct and immediate cause of the disease . CORRELATION OF INFECTION WITH PATHOLOGY In the patient in whom he found flukes. and was convinced that the presence of worms in the bladder was a prerequisite for urinary disease.30 It is quite possible that Bilharz was sometimes dealing with cases of amoebic .. leatherlike areas of mucosa covered with salt crusts. Bilharz apparently recognized no partcular pathology. in the earlier lesions we saw areas surrounded by varicose capillaries coated with mucus and blood. but the n qualified this remark by adding that cadavers of such patients were rare .. it became apparent that some of them were dilated blood vessels containing adult schistosomes. Ferrisea tenuis 91. Dr Lautner. Bilharz had a second case in which there were not only bladder tumours. believe that the worm is related to a large extent to the frequency of bladder ailments. 32 When some of the larger lesions were cut into. however. either singly or in clumps. haematobium was the cause of extensive damage to the urinary tract: I no longer have any doubt that the worms cause the changes in the bladder. for he had two patients with this latter condition i n whom eggs could not be found. Earl y lesions on the other hand. One week later. I have not been able to reach a decision concerning these important questions. the bladder excrescences contained no worms bu t eggs in spherical heaps were embedded in the mucosa.but not solely responsible. In May of that year (1852). ureter and the seminal vesicle and so on. India in 1952 by Gadgil and Shah 92. but also extensive dysenteric changes in th e intestine. In the older lesions. he was less certain abou t their role in dysentery. they found: lentil. calculi and also certain renal diseases. spongy excrescences. harboured large numbers of S.Schistosomiasis haematobia 205 Bombay. In March of the following year (1852) . When the y opened the bladder. soft. The same eggs had been noted previously in th e bladder by one of their colleagues. Bilharz again wrote to von Siebold stating his view that S. for he made no comment on this subject in his first letter about this infection to von Siebold. haematobium eggs. In this patient.to pea-size. therefore. but he had not been able t o explain their nature. he and Griesinger fou nd evidence of bladder involvement when they performed an autopsy on a boy who had died from meningitis. (and) often. there were simply: foci of hyperaemia. He descri bed the various changes that could be found in the bladder. Bilharz believed that these changes could be attributed to inflammation an d extravasation of blood consequent upon invasion of the small blood vessels by schistosomes and deposition of their eggs.. Griesinger understood that these disturbances in the function of the urinar y tract sometimes led to a generalized chroni c disease. . The mucosa was somewhat swollen. Griesinger connected vesical schistosomiasis with the urinary lithiasis endemic in Egypt "In addition... he described "polypoid patches of the mucosa which were.covered either with viscous mucus or with a soft grayishyellow. muscular hypertrophy. the eggs of the Distoma were found.100 There were countless transitional forms or intermediate stages between these tumours and the diffuse lesions. mansoni... he realized that urinary schistosomiasis was sometimes associated with intestinal disease . He also recognized a third type of lesion: In some instances solitary clusters of pea-to-bean size. Like Bilharz... for he did not differentiate between the two. pyelitis. published a classic report on his findings in the 117 cases of schistosomi asis that he had encountered during the course of 363 autopsies. Griesinger also noted that all these changes were often seen in the ureteric mucosa and sometimes even in the renal pelvis..100 He noted that the urine in the bladder of these patients was generally light and clear. pneumonia.. It seems most likely that those patients with intestinal schistosomiasis as well as vesical schistosomiasis were infected concurrently with both S. mansoni...100 In the same manner as Bilharz. In 1854. fatty degeneration.. large urinary stones often formed in the kidneys.. Griesinger. dysentery and anaemia. there may be spindle-shaped or sac-like dilation of the lumen. culminating in death from debilitation..and often. He realized that th e consequences of the ureteric lesions were much more serious: Deposits on the mucosa and frequent thickening of the submucosa caused stricture of the ureter. labelling them all a s eggs of S. hemorrhagic exudate. and/or urinary retention with its complications. haematobium. so he concluded that the former simply represented more advanced degrees of same process. for neither of these conditions nor their causative agents were recognized at that time. In cases where these changes had been present a longer time.. en masse.206 A History of Human Helminthology or bacillary dysentery. They were wart-like or fusiform..containing many fine extravasations of blood..showed a brittle crust on th e surface"100. In more advanced cases. What is less clear is how many of the eggs in the intestines that he saw were those of S.discolored. hydronephrosis and complete atrophy of the kidney parenchyma were found. in addition. yellowish or ecchymotic papillomata or vegetations one to three lines high were found on the mucosa. haematobium and how many were S. Bilharz's colleague. ureters and bladder with serious consequences" 100. In these secretions. In the mildest cases.. haematobium and S. or directly into the lumen of the urinary tract. He wrote: "I have no hesitation in affirming that cancer of the urinary bladder is the irritatio n cancer of Egypt. H e postulated that male worms carrying a pregnant female in the gynaecophoric canal migrated against the flow of blood to the small vessels of the vesica l venous plexus and that the female worms then deposited ova in a gelatinous substance. in the bladder of patients with schistosomiasis. Following thes e pioneering studies. and mucosal ulceration. his discovery of schistosome ova in the blood of the left side of the heart caused him to remark that "th e transportation of the worms or at least their eggs into the general circulation and to essential organs must be kept in mind" 100. Urinary schistosomiasis is sometimes complicated by the development of neoplasia. Similarly. He acknowledged that further investigations were needed t o determine whether the worms were merely an irritant in persons predisposed to cancer or whether there was a direct aetiological relationship between the worm infection and cancer. 20 of the pe rsons had died of "bilious typhoid". polypoid growth of the mucosa. mansoni infection and is described in the next chapter. remarking that he had not been able to trac e any relationship between schistosomiasis and cancer of the anus. the histopathological changes of chronic inflammation and fibrosis around eggs were described by a number of investigators e. so he remarked cautiously that there was not necessarily a direct link between schistosomiasis and dysentery or typhoid fever. haematobium and pathological changes in the urinary system 31. the eggs acted as foreign bodies and stimulated an inflammatory reactio n which resulted in the lesions seen. He suggested that the adult worms and eggs blocked blood flo w causing rupture of the vessels and extravas ation of eggs. These descriptions of the gross morbid anatomical changes in urinar y schistosomiasis have hardly been improved upon since. Ferguson went on to contrast this with intestinal schistosomiasis. In 1856. The pathogenesis of these lesions is similar to that which occurs in S. induration and calcification of th e mucosa. This was first suggested by Harrison in Liverpool in 1889. either into the mucosa itself. usuall y carcinoma. h e reported that four out of five specimens of bladder schistosomiasis sent to him from Alexandria by Mackie were complicated by the presence of squamou s carcinoma106. rectum o r . Zancarol205. He classified the pathological changes in the urinary system into four groups: catarrha l inflammation of the bladder and ureters. If trapped in the tissues. All of these changes Bilharz attributed to the presence of eggs in the mucosa.g ." 83 To underscore his point. A similar case was reported by Albarran an d Bernard in 1897 3.Schistosomiasis haematobia 207 having found that 50 of his 117 cases with urinary schistosomiasis had acute or chronic dysentery. Bilharz published a lengthy paper on the relationship between S. He suggested that an y relationship between schistosomiasis and both hepatic abscess and live r atrophy was worthy of investigation. Finally. In 1911 Ferguson set the association on a firmer foundation when he described a series of 40 cases of malignant neoplasia. was the sign which gave Bilharz the clue to the diagnosis of schistosomiasis when later that year. With respect to the location of the adult worms. increasing o n occasion to vehement burning or colicky pain. Griesinge r listed haematuria. and continued to pass eggs for at least another 28 years 51. in fact. By a process of elongation . . one well-known English zoologist and physician was infected whilst on a naturalist expedition between th e Limpopo and Zambesi rivers in 1878. This view was disputed later by Brumpt who could see no role for the spine 39. In his review of urinary schistosomiasis in Egypt. he first found eggs in the urine of a living patient. Lik e Griesinger. Fairle y believed that the spine engaged the vessel wall. The adult worm then withdrew slightly and the overdistended venul e contracted down upon the egg. then rent a tear in it under the forces of the bloodstream.208 A History of Human Helminthology sigmoid colon. passage of mucus in the urine. mansoni . frequency of micturition . the largest numbers were present in the vesical and uterine venous plexuses. and so the process was repeated. haematobium adult worms in blood vessels wa s studied in anaesthetized monkeys by Fairley 78. Fairley showed tha t although they could be found in the portal and inferior mesenteric veins. When the time for egg-laying was at hand. the recognition of these effects is described in chapter 9. This.80. The pathological changes in the liver and lungs in S. I n this situation they may live for many years. especially to stones in the ureter 31. enlargement of the kidney. and was thus extruded into the perivenous tissue. he also thought that infection predisposed to urolithiasis. He observed that the adul t worms moved with a peristalsis-like action of the body and with the aid of the ventral sucker. but long-lasting and recurring frequently. then ejected an ovum. RECOGNITION OF THE CLINICAL FEATURES It must have been clear to Bil harz and Griesinger when they first found ecchymoses and blood clots in the blad der of a boy with vesical schistosomiasis that passage of blood in the urine would be a promi nent feature of schistosomal infection. haematobium infections broadly resemble those caused by S. Bilharz later re-emphasized these points. the last being usually only a slight admixture of blood. and haematuria. the female worms left their male partners and retrogressed against the portal bloodstream to the small venules. each worm then worked the anterior truncated part of its body into a vessel of smaller diameter than its own. The behaviour of S. making particular mention of a feeling of pressure and tenderness in the lower abdomen. with the spine pointing backwards into the current of blood. septicaemia and acute exacerbation of various obscur e and undiagnosed bladder and kidney ailments as the ways in which patients with the infection could present clinically 100. pyelitis. but sometimes the "veins" would block the urethra and caus e obstruction for a few minutes.. description of the use of a basket to cover the penis as a protective measure against this affliction has been found in the Papyrus Ebers172. Indeed. myalgia. 176 These symptoms and signs were again well-recognized in British troops i n South Africa during the Boer War and in Imperial soldiers in Egypt durin g World War I. headache. it became possible to recognize earlier descriptions of schistosomiasis. haematobium was provided when Ruffer found large numbers of calcified ova in the kidneys of two mummies dating from between the XVIII and X X Dynasties (1250-1000 BC) 181. His patient complained that after micturition. In this person.manifested itself among the soldiers of the French Army . Often even. Once the clinical manifestations of S..C. it became clear that the epidemic which afflicted Napoleon' s troops in Egypt at the turn of the century before Bilharz discovered the worm and which was described graphically by Renoult was none other tha n schistosomiasis haematobia: A most stubborn haematuria. 75 troopers of the Australian light horse wer e infected by bathing whilst stationed at Serapeum and at Tel-el-Kebir in 1916.. a little blood . The early toxaemic stage occurred four to ten weeks after infection in more than half of th e soldiers and was characterized by fevers.. he had occasional twinges of pain in the loins102. the latter becoming thick and bloody.1900 B. Harley later came to realise though that many robust person s (colonists) in South Africa were infected with the parasite without an y apparent detriment to their health 105. rigors..1500 2. For example. It has even been postulated that urinar y schistosomiasis was the basis of Joshua's curse and the cause of th e abandonment of ancient Jericho 111.)168 referred to haematuria. then terminal haematuria supervened . Many Egyptologists have concluded tha t the .disease mentioned in ancient texts such as the Kahun papyrus (c. although the Egyptians were probably no t familiar with the worms themselves.Schistosomiasis haematobia 209 These symptoms were similarly well-described by Harley in London i n 1864 in connection with his patient with the "endemic haematuria of the Cape of Good Hope". Moreover. the last drops are pure blood. haematuria was so common that it was mentioned some fifty times in papyri known by 1951 185.C. Moreover. A later stage appeared three months after infection. the last contractions of the bladder are accompanied by the most lively and piercing pains. or some dark "veins" (presumably blood clots) appeared with the last half ounce of urine. haematobium infection were defined. undoubtedly of schistosomal origin .109 B.the continual and very abundant sweats diminished the quantity of urine. urticaria and emaciation lasting from t wo to five weeks. never exceeding a teaspoonful . The clinical manifestations were divided into two phases. sweats. Formal proof that the ancient Egyptians played host to S. Similarly... The sickness gives sharp pains in the regions of the bladder. in 60% of the patients.) and in the Papyrus Ebers (c. the earliest symptom was a burning urethral pain on micturition. the urine itself was never bloody. A rather greater blood loss was estimated by Farid and his colleagues who used red blood cells radiol abelled with 59Fe: they calculated that between 2. further nodules developed and one was excised. One or both kidneys will be found enlarged and tender. A very small quantity of water is voided at a time. The kinetics of infection and the consequences of urinary schistosomiasis were particularly well-illustrated by a self-inflicted infection with S. is very irregular and stony. After a further week. and schistosome eggs were seen in the seminal fluid and in a plug of mucus in his stool. infected himself by applying eight cercariae from eight different specimens of B. pus and shreds of m ucosa were seen in the urine. Ova ap peared in the urine on the 106th day. more cercariae wer e similarly placed and 61 papules were seen 24 hours later. truncatus to the skin of his forearm. ranging between 6% and 16%. feeling that the support affords him some alleviation of his pain. Eggs continued to be excreted in the urine and faeces. Micturition was frequent an d painful and blood. and may extend as far as the umbilicus and to any extent laterally. An evening pyrexi a persisted and Barlow felt ill and prostrate. although the drug did no t eradicate the infection completely 27. nausea. haematobium. Barlow estimated that he was infected with a minimum of 224 cercariae. On the following day. thus confirming his previous observation that dermatitis may occur i n schistosomiasis haematobia 26. wheeze and cough. Maddern described th e possible devastating consequences: He has constant micturition. While mild or moderate symptoms were the rule.210 A History of Human Helminthology after another one to four weeks 77. Eleven weeks after the major exposure on 14 June. .. he placed eight more cercariae from the same snails around his umbilicus. Ten months after infection. spermatozoa wer e found in his urine. 147 sma ll red papules were seen on the next day. which is not at all tender. which is very offensive. a hard mass may be felt in the suprapubic region. and the much dilated and thickened . it was realized that very intense infections may cause severe disease. Gerritsen and hi s colleagues showed in 1953 that between 1. The amount of blood lost in the urine in patients with schistosomiasi s haematobia has been investigated on several occasions. He very often carries his scrotum in his hand. revealing a pair of adul t schistosomes. a nodule which discharged eggs appeared on the scrotum.1 ml of blood was lost per day in African males 94. this caused a fever. Blood and mucus appeared regularly in the stools.3 and 6. he was treated with fouadin. Claude Barlow (who had earlier infecte d himself with Fasciolopsis buski). really an incontinence and dribbling. Th e numbers of eggs excreted were reduced greatly. wit h 20. Thus. After 20 weeks. many cercariae from another six snails were again applied near the navel. Two weeks later...000 being passed daily in the urine alone. Barlow's blood eosinophil level was increased.6 and 126 ml of blood were lost each day in infecte d Egyptians82. dark brown in colour .On examining the abdomen. and turbid. with pain in the penis and deep down in the perineum near the rectum. On 31 May 1944. he developed a mild fever.000-30. whereas in the latter it is not uncommon for the patient to pass fifty.150. Griesinger later referred to this epochal observation: The eggs of the Distoma were found by Dr Bilharz while microscopically . distorting false elephantiasis of the scrotum and perineum might supervene 153. On the whole. leathery areas of bladde r mucosa which contained innumerable calcified ova but no living adult worms or fresh eggs31. often intermittently. he felt a rough surface in the bladder which he was able to palpate between his finger in the rectum and a catheter i n the bladder. he did not reject the possibility that spontaneous cur e might occur.153 In addition. In severe cases the daily average of evacuated ova greatly exceeds this estimate. or for that matter. He contrasted 'slight' and 'excessive' invasions thus: In cases of the former kind not more than a dozen or so of the parasite's eggs will be passed at each act of micturition.Schistosomiasis haematobia 211 ureters may be felt through the usually thin abdominal wall. unfortunately. for he often encountered pigmented. more dependent upon associated disorders than upon the actual number of parasites present. he told von Siebold in a letter dated 2 August 1852 "I found fresh eggs in the urine of a young man who had moderate haematuria of unknown aetiology" 30. Maddern noted that urethral fistulae and a destructive. the bladder will be felt firm and contracted. a hundred dozen bilharzia eggs at a time. he thought that the latter was more likely. Cobbold went on to suggest that: the severity of the symptoms and consequent dangers are. Bilharz recognized that the disease may last for many years.59 Infections in British troops in the South African war revealed that the disease was more prolonged than had hitherto been believed. he was unable to examine the urine of this patient. as a rule. Nevertheless. Both Bilharz and Griesinger thought that death was ofte n caused by intercurrent illness. Cobbold was among the first to realize that the severity of clinical manifestations bore some relation to the worm burden. but it was concluded that mortality arising from infection did not exceed 1% in the 466 soldier s studied107. With respect to prognosis. On rectal examination. In another patient. thus indicating that either the worms lived for a long time. On introducing a sound. however. Bilharz made a provisional diagnosis of vesical schistosomiasis i n one living patient and proved the diagnosis in another. it can often only be passed just beyond the neck of the bladder into a very much contracted cavity. Symptoms persisted for between five and thirteen years. In the former case. and bimanually the great thickening of and around the bladder will be well appreciated. and this view was supported by practitioners in South Africa who claimed that they had never seen anyone die fro m schistosomiasis 4. 59 Nevertheless. DEVELOPMENT OF DIAGNOSTIC METHODS In 1852. or that reinfection was common. but wit h inconclusive results 31. infiltrated swellings of th e mucosa. although this has been dispu ted by others. Many attempts have been made to diagnose schistosomiasis by immunological methods. but he was less sanguine abou t prospects for eradication of the worms. An increased number of eosinophils in the peripheral blood was found in a single patient by Coles 60 in 1902 then the presence of eosinophilia wa s confirmed in a series of patients by Douglas and Hardy 72. but that local injections of emulsions of oil of male fern o r potassium iodide in a strong infusion of wormwood or quassia into the bladder . Harley reported the effects of his treatment for endemi c haematuria. THE SEARCH FOR EFFECTIVE TREATMENT The early investigators recognised the need for effective anthelmintics to cure schistosomiasis. Many investigators believed that eggs could be found most frequently in the terminal urine. and fungating vegetations of the mucosa 162. he noted three types of lesions. have the advantage of delineating the natur e and severity of damage to the blad der. Griesinger suggested that calomel and oil of turpentine might be effective. while the other suffered from more severe disease. and that perhaps certain foods such as onions and garlic migh t exert a beneficial effect 100. a rapid concentration technique using filters has been developed for rapi d quantification of eggs in the urine 171.166. An alternative but more complex method of making the diagnosis whe n facilities became available was by endoscopic biopsy of lesions in the bladder. one of whom had a light infe ction. Structural damage to the urinary system can on ly be outlined radiologically. In 1917. for he thought it would be difficult for drugs to reach them in their domicile in the veins. In 1919. Bilharz indicated that local pains usuall y disappeared rapidly after the use of opium. In 1870. however. He found that general therapy with potassium iodide and henbane was of little use. In more recent times. In the latter patient. Minet in 1915 appears to have been the first person to examine the bladder cystoscopically. Fairley reported the development of a complement fixation test fo r antischistosomal antibodies 79 then he and Williams described an intradermal test for the infection 81. The diagnosis can be established with this finding alone 100. This technique does.212 A History of Human Helminthology examining the urine of a boy who developed haematuria during convalescence from typhoid fever. He tried on a couple o f occasions to poison worms in diseased specimens with calomel. He investigated tw o soldiers. Diamantis and Lotsy showed calcification of the left ureter an d bladder due to deposition of eggs in a plain x-ray of the abdomen 70. Intravenous pyelography provides a much more sensitive and complet e definition of the urinary tract and has been used in the last few decades 85. smal l yellow granulations likened to grains of millet. that antityphoid serum may be of use 191. th e famous chemist115. Cobbold's describing the treatment as heroic. I fear. Cobbold's comments drew a vociferous reply from the injured J F Allen. Day and Richards (1912) in Cairo assessed th e effectiveness of the drug in patients with urinary and/or intestina l schistosomiasis and found it wanting 66. He remarked wryly tha t since patients did not return after this agonizing treatment. acute nephritis with secondary pericarditis. and in a case with which I am unfortunately only too well acquainted. Many observers were not convinced of its efficacy . however. the proponent o f this therapy concluded that the treatment was successful 4. cystitis. 5 In the interim. Stock suggested.101 Cobbold's "rational" treatment also met with criticism. and followed by cystitis. on the basis of a couple of coincidental observations. The so-called "rational plan" (presumably Cobbold's) consisted o f general support by way of a nutritious diet and the administration of iron and quinine 58. then given wide publicity by Erlich. so timid and ultra-conscientious that he would consider it heroic to use enemata in the treatment of ascaris vermicularis in the rectum. so he hardly thoug ht that improving the general condition of the patient was likely to result in cure 105. none of these drugs was of great value. Salvarsan enjoyed a vogue after being introduced in 1911 by Dr Nicola s Joannidès. Fouquet in Cairo claimed that extract of male fern was beneficial in fifteen of his patients 87. medications such as a saturated alcoholi c solution of santonin were injected into the bladder. Cobbold classified treatment into thre e categories. but they are efficacious in the one case as in the other. he is. A few years later (1882). then emphasized the toxicity of such therapy: Dr Allen allows that acute cystitis is a common result.Schistosomiasis haematobia 213 via a catheter were beneficial 104. and in only two of them did the numbers of ova in the urine diminish even transiently 182. Similarly. and probable life-long ill-health have been the unlucky consequences. It is to these injections Dr Cobbold objects so much. In 1888. T hus. but as experience and common sense both point to their use. but proved to be of little use. Schrecker had fou r longstanding and four recent cases. Harley remarked that he could see no reason why the parasite should not flourish all the more when the host was healthy. more difficult. the exemplar of the "heroic" system: Those who may have to treat cases of this kind must not be deterred from using injections into the bladder by Dr. In 1906. a physician in Cairo. and an eminent surgeon in Cairo wrote in April 1917: "Until now there . Sonsino then reviewed thes e arguments and concluded: "as yet. In the "heroic plan". Thymobenzone was advocated in 1916177. The "do-nothing plan" was based upon the assumption that the patient would outgrow th e disease. it is to be hoped that even he may be induced to adopt them. For example. H e lamented the lack of any concrete evidence given by Allen for the efficacy of local treatment. Injections into the bladder are more painful. Cobbold's views had been supported by FH Guillemard wh o wrote from Japan expressly to dissuade the adoption of Allen's regimen. we have no means of curing the infection of Bilharzia better than it is done by nature" 188. including Cawston (1919).000 persons treated as outpatients in a tent-annexe at the Kasr-el-Aini Hospital in Cairo: 88% of these patients had urinary schistosomiasis. 1/2gr to 20m aq. or longer if symptoms intervened. Christopherson. He found that 13gr was the smallest curativ e amount. Sudan. The injection was given into one of the conspicuous veins at the bend of the elbow. Since it was thought unlikely tha t reinfection had occurred. Innes (1919) and Taylor (1919) who also reported encouraging results in small series of patients. dark-coloured and failed to hatch miracidia in water. Christopherson followed up this serendipitous observation in other patients.214 A History of Human Helminthology is no curative treatment for schistosomiasis. He was wrong. Fairley (1919). distill. The solution used was tartar emetic. JB Christopherson reported that the antimonial compound. these data were interpreted as indicating that th e primary effect of the drug was the destruction of ciliated embryos within their shell. ova reappeared. distill. but that 24gr or more were usually needed.47 Christopherson also noted that it was essential to watch for signs of acute to chronic poisoning. and diluted with 2 vols of aq. the schistosome ova becam e shrivelled.46mg) given over 15-30 days were necessary to achieve a "killing dose". tartar emetic (antimonium tartaratum. approximately 30 grains (O. and found tha t after intravenous injection of tartar emetic. Day was able to report an analysis o f toxicity and effectiveness of the drug in 1. Day also noted that after the first weeks of intensive treatment. with a fine needle was used. had treated a patient wit h kala azar (visceral leishmaniasis) with antimony. record syringe. The effectiveness of the drug was confirmed by Lasbrey and Coleman in Cairo in the same year. but that two to three months later. Altogether.48. Christopherson's regimen was taken up enthusiastically by a number o f physicians. The patient lay down for an hour on a bed after the injection. He noted that during thi s course of treatment. the parent worm requiring a larger dose to achieve a lethal effect 65. the eggs disappeared completely from the urine or faeces. The injection was repeated and the dose increased by 1/2gr every other day until 2gr was reached and this was continued until 30gr had been injected. who was principal medica l officer at the Civil Hospital in Khartoum. rosy-faced race" 49. Low and Newha m (1919). results appeared excellent. and I think it is far from possible to find one in the near future" 18. so that the people would become a "clear-complexioned. those symptoms that were due to schistosomiasis (wit h which the patient was concurrently infected). also with a series of 1. After a fe w weeks. Further experienc e showed him that the drug was not only able to kill the adult worms. but also the embryos in the ova in the tissues 50. In the following year.. were alleviated. By 1921.000 cases. potassiu m antimony tartrate) was of great value in the therapy of both urinary an d intestinal schistosomiasis 47. Of those who finished th e . So convinced of the efficacy of th e treatment was Christopherson. that he wrote that it may be possible to rid the scourge of schistosomiasis from Egypt. at the time of use. He described his technique as follows: A 10 ccm. 70% were pronounced cured and they remarked that: 215 the successful treatment of complications dependent upon bilharziasis. stibocaptate.125. and was then used in schistosomiasis haematobia in 1956 89. In the week following Christopherson's paper. Lithium antimony thiomalat e (anthiomaline) was introduced in 1935 and could also be given b y intramuscular injection. when an effective drug was promulgated. In half of these persons. the y . and that had they kept to certain rules. Similarly. He reiterated this claim two years later. Following the introduction of tartar emetic. h e claimed that he had used the drug empirically because of its effectiveness in some other disease caused by animal parasites 151. Sodium antimonyl dimercaptosuccinate (TWSB. a number of other trivalen t organic antimonials were developed. and these disappeared after administration of tartar emetic. Sodium antimonyl tartrate (SAT) wa s claimed by some to be better tolerated than the potassium salt. is enormously facilitated by the elimination of the causative factor. Similarly. In 1936. seeing that the infection would not have killed the patients in that time. Khalil estimated that antimon y killed about 2. these compounds. astiban) was introduced b y Friedheim and colleagues in 1954 for schistosomiasis mansoni 90. quoting from the 1915 edition of his book Biology and treatment of venereal diseases : I should like to mention that I have had great success in treating cases of bilharziasis with intravenous injections of antimony. A major problem with the antimonials was the severe.000 persons in Egypt each year122. The advent of st ibophen (fouadin.133 The effectiveness of the drug was demonstrated amply by Shaw in 1921 who studied the cystoscopic appearances in 23 patients with schistosomiasis who were undergoing treatment. neoantimosan) in 1929 was hailed as a considerable advance because it could be given b y intramuscular injection and as it was at first thought to have higher cure rates and less toxicity that tartar emetic 124. though less toxic. pentavalent antimonials being found to be ineffective in schistosomiasis.Schistosomiasis haematobia course (20gr). such as urinary fistulae and rectal papillomata. but more in the nature of an anecdote. a lette r was published by JE McDonagh in which he recalled that he had use d antimony in 1911 and had eliminated ova from the urine in 23 cases. Sodium antimonyl gluconate (triostam) given b y intravenous injection had variable effectiveness 75. sometimes fata l toxicity associated with their use. were less effective than tartar emetic. there had been activ e nodules present before therapy. others tried to cash in on the credit. Unfortunately. Not surprisingly. infiltrations and signs of subacute cystitis subsided . it could not have been more effectivel y pigeon-holed. This appalled Diamantis who considered such therapy monstrous. Wiley wrote that a case of urinary schistosomiasis had been treated in a like manner at the Australian Dermatological Hospital in Cairo in 1916 203. and even the fibrotic areas appeared to improve and become pink 184. 152 This drew forth the riposte that although it was the earliest record of the use of antimony in bilharziasis. but this view was not accepted universally. oral preparations wer e developed. Erian reported that he had used large doses of e metine in 50 patients with both forms of schistosomiasis and claimed to have no failures 76. it became known that Dr H Mauss in Germany had synthesized a new series of compounds known as miracils . there was a spasm of interest in th e anti-schistosomal properties of acriflavine 84. emetine in its various forms did not achieve the long lasting popularity of the antimonials as it was generally considered to be both less effective and too toxic for outpatient use. Nevertheless. promulgated the use of emetine. particularly by continental European workers.2 grams injected intravenously in aliquots over 10-12 days 193. In the following year. In the middle of the 1930's. In fact. The article by Tsykalas stimulated a letter from Mayer who claimed priority in the use of the disease. Diamantis reported that emetine was of value in a series of patients with schistosomiasis 68.128. after declaiming the use of antimony as barbarous. the virtues of emetine in the treatment of schistosomiasis were sung. The first major competitor for the antimonials was emetine. mansoni in mice and in monkeys when given orally19. They treated 100 patients with S. Mayer treated a case of urinary and intestinal schistosomiases b y subcutaneous injection of emetine and found that blood disappeared from the urine and stools. In 1919. provided that the emetine was given in a total dose of 1. In 1921. Tsykalas responded to this by stating that he himself had given it intravenously in 1914. At the end of the Second World War. In 1917. Clinical trials were then carried out in Southern Rhodesia (Zimbabwe) and in Egypt. Alves and Blair introduced "intensive therapy" with antimonials. controversy then ensued as to who first introduce d emetine therapy.0-1. at almost the same time as tartar emetic was introduced. These problems with toxicity led to a continuing search for safer and more effective schistosomicides. Nevertheless. Tsykalas. The therapeutic results were excellent and the apparent absence o f toxicity was remarkable 9. He indicated that 90% of 2. Mayer considered the drug to be inferior to antimony 159. haematobium and S. but that Tsamis of Alexandria had in fact used it as early as 1913 194. but because of the political circumstances.000 patients showed a complete and lasting cure. lucanthone) was shown b y Kikuth and Gönnert to be active against S. haematobium was more susceptible to the drug than . miracil D (nilodin. Gordon showed that emetine periodide was effectiv e when given orally 99. mansoni infections with full doses of sodium antimonyl tartrate frequently within a period of only two days. In order to facilitate administration of the drug. In 1946. and it was found that S. and the patient showed great improvement 158. One of these preparations.216 A History of Human Helminthology might have looked for a natural cure 69. they were not able to publish details of their experiments until subsequently 127. but this proved to be short-lived 126. saying that he recommended it and gave it subcutaneously in 1915. As with antimony. In 1926. and was sometimes toxic to the liver 21.201. hycanthone. Subsequen t clinical studies showed that it was highly active against both S. a number of investigators reported that it was active against S. There was. Hycanthon e could be given by a single injection. Lambert had reported that a new drug. niridazol e (ambilhar) was active in mice infected with S. Subsequent studies showed that the agent was als o effective against S. by the early 1970's there were three major therapeutic agents used in urinary and intestinal schistosomia sis . however. In the following year. S.114. Later that year. then in 1969 it was reported to be active against human S.Schistosomiasis haematobia 217 was S. praziquantel (biltricide. droncit) against all three of the major schistosome species infecting humans 64. a fourth drug which was useful in urinar y schistosomiasis. in 1964. Niridazole had the advantage of ora l administration and was effective. This observation was confirmed by a number of investigators 86. another miracil derivative. haematobium 116. but was prone to provoke neuropsychiatric complications. Praziquantel promises to become the drug of choice in the treatment of all forms of schistosomiasis. haematobium in Zambia63 and against S. mansoni and S. particularly if there was hepatic insufficiency. Cerf and colleagues indicated that th e organophosphate compound. a pharmaceutical company collaborated with the World Health Organization to assess. it had very littl e toxicity. hycanthone and niridazole . In the late 1970's. mansoni 131. This drug had the added advantages that it could be given orally and in a single dose. Improvements in surgery and anaesthesia facilitated surgical intervention where necessary. mansoni 34. haematobium infections as well 53. dipterex (trichlorophone. but it needed to be given intravenously. . mansoni but less so than against S.170. and th e toxicity was sometimes severe. japonicum in experimental animals 97. Thus. Katz an d Pellegrino showed that it was effective in patients with schistosomiasi s mansoni118. the effectiveness an d toxicity of new agent. mansoni 110.192. In 1897 . haematobium. The drug was given orally an d was well-tolerated 132. but the drug was shown to b e inactive against S. In 1962.antimony. the course was long. but eradicated the infection in onl y 50-65% of patients. Moreover. The consensus of opinion was that tartar emetic was the most effective drug in bringing about a parasitological cure. Meanwhile. This drug had been identified in 1972 from a group of heterocyclic pyrazino-isoquinoline derivatives an d was found to have unusually b road anthelmintic activity.each with its supporters and opponents. Occurring concurrently with these medical developments were changes in the surgical management of urinary schistosomiasis. metrifonate) wa s effective in patients with schistosomiasis haematobia 45. was reported to be active against schistosomes in experimental monkeys 169. In 1967. in a uniform manner. In 1977. mansoni in Brazil119 . its efficacy in urinary schistosomiasis was reported following a clinical trial in Portuguese Guinea (Guinea-Bissau). This especially flowed from the view espoused by Looss that direct infection with miracidia without the mediation of a vecto r takes place. lithotomy for th e removal of calculi. In 1903. UNDERSTANDING THE EPIDEMIOLOGY S. however. autoinfection could occur for example in household baths. and infection could spread to any part of th e globe144. drainage of the bladder by perineal puncture for acut e retention of urine or in very late stages of the disease. infection could occur in both towns and in rural areas if puddles were contaminated. Nevertheless. the geographical distribution of urinary schistosomiasis was recognized. then sprea d together with the vector snails along the Nile and out into the Middle East via the trade routes 167. has reduced greatly the need for surgical intervention. In 1918. In particular. and found that the procedure not only cauterized the lesions but also appeared to kill egg s infiltrating the bladder wall 67. water woul d become safe automatically after 30 hours if the local population was removed (because miracidia have only a limited life span). it became obvious that transient water .218 A History of Human Helminthology Curtis described partial resection of bladder for a vesical ulcer caused b y schistosomal infection 62. These concepts underwent a radical revision when Leiper showed in 1915 that infection only occurred via a mollus can intermediate host 134. the increased prevalence in males and the young was realized. as was first shown when Cobbold found the parasite in a monkey in London 54. plus removal o f schistosomal tissue if possible. The introduction of effective chemotherapy . Milton reviewed the surgical management of schistosomiasis haematobia and recommended that cystitis be treated b y bladder washouts with mild antiseptics such as quinine. It is thought that schistosomiasis may have first evolved around the great lakes of East Africa. failure to understand the life cycle led to a number of incorrect assumptions about the epidemiology of infection. and excision of fistulae 160. It has been suggested that human schistosomiasis may have evolved at the same time as there was a shift in human populations from hunter-gatherer economies t o societies based upon domestic agriculture. Some of the initial ideas on the epidemiology of schistosomiasis have been discussed earlier in relation to the various theories on the transmission o f infection. Desnos investigated the effects of cystoscopic high frequency diathermy o f papillomatous and epitheliomatous gro wths of the bladder wall. haematobium sometimes occurs in subhuman primates. and the association with water was commented upon. The consequences of this idea were the beliefs that transien t collections of water were dangerous if contaminated whereas large bodie s were not liable to be infective (because of dilution). In view of the time required for cercariae to develop. since this parasitism requires a stable relationship between parasite a nd host. and infection could only spread to parts of the globe where susceptible snails were present.2%). have bee n constructed to enhance economic development by improving water supplies and generating electricity.Schistosomiasis haematobia 219 collections were quite safe whereas permanent collections were potentiall y dangerous if the vector was present. in some places reaching epidemic proportions 23. social. Many examples of these changes have been recorded. whether for economic. These fluctuation s depended upon changes in water resou rces93. the age and sex distribution of the infection. rising from 3. for there is no significant animal reservoir of infection . infection in towns was possible if there was a supply of unfiltered water from contaminated water sources. irrigation only at the flood of the Nile . Urination in water sources by infected persons and contact with that water . several will be cited here. scant regard was paid to the potential health hazards. In the final analysis. autoinfection was impossi ble. Much effort was then expended on determining the prevalence an d intensity of infection in various endemic areas. but th e increased prevalence and intensity in males and in children was generall y confirmed. fo r infection increased in some areas and fell in other. In Egypt. had almost disappeared (2. and the occurrence of schistosomiasis has increase d enormously. which was once commo n (74% of the population infected). . Before building the Sennar dam across the Blue Nile to irrigate the Gezira Province of Sudan in 1925.2% to 73%. are essential for maintenance of the life cycle of the parasite and play a major part i n determining the prevalence and intensity of infection in a given population 196. Unfortunately. Not only have changes occurred around the lakes themselves but along the Nile the pattern of schistosomiasis has altered downstream. though. i. however. the habits of the human population are o f crucial importance. schistosomiasis haematobia. introduced by Egyptian labourers. domestic or recreational reasons. increased the infection rate between four. Lake Nasser in Egypt and Sudan.e. Bulinus species were present in all the waterways of the system and infection. a number of great man-made lakes in Africa including Lake Volta in Ghana . and Lake Kariba in Zambia. These effects were ascribed to changes in th e densities of the respective vector snails consequent upon the changes in th e water-flow pattern of the Nile following construction of the Aswan High Dam and creation of Lake Nasser 1. In more recent years. in one village surveyed in 193 5 and again in 1979. The frequency of infection ranged from near zero to 100% in different localities. was spreading 112.and forty-fold in a number o f villages in the three years from 1934 to 1937 123. Within two years. and the prevalence and density of vector snails. however. the introduction of perennial as opposed to basin irrigation. prevention of urinary or faecal contamination of water would have no effect for som e months. but th e prevalence of schistosomiasis mansoni had shown an almost reciprocal effect. Urinary schistosomiasis was not a static process. schistosomiasis haematobia was almos t non-existent in that part of Africa. 12 This was good advice. Methods for th e control of infection among the general population hinged upon whether or not infection was direct or occurred via an intermediate host. however. The demonstration of transmission through snails. This was and is an almos t impossible task. it could lead to the eradication of the disease in the course of a few years. He suggested tha t appropriate measures included periodical drying of waterways in agricultural areas to kill snails by drying. 146 This was easier said than done..135. and eradication depended upon education and complete sanitary control throughout the country. and that personal contact with any kind of unfiltered water was risky 134. despite an inadequate understanding of the lif e cycle of the parasite. been left unprovided with any filters. and storage of water before supplying it t o towns134. h e turned his attention to a consideration of both personal prophylaxis (wit h particular reference to troops) and control of the infection in general. however. and that if this fact were properly exploited. Wit h respect to the former.. provided a link in the chain which could be attacked without the cooperation of infected individuals. The editorial followed a minor epidemic o f schistosomiasis among the staff of the Eastern Telegraph Company at Suez.220 A History of Human Helminthology THE EVOLUTION OF PREVENTIVE AND CONTROL MEASURES The association of schistosomiasis with water was so strong that an editorial writer in the British Medical Journal of 1882 was able to suggest correctl y effective control measures. the writer was concerned that a similar fate might befall British troops then situated in that country: If drinking directly from the canals. Irrespective of the mode of transmission. it seems. he studied various physical and chemical measure s designed to kill cercariae and concluded t hat unfiltered water was safe if stored for 48 hours. and remembering the affliction of French tr oops by endemic haematuria during the expedition of 1799 to Egypt. however. for many o f whom daily contact with water was necessary for survival. and water well-boiled or well-filtered. with the sustained cooperation of every individual being essential.be alone used for drinking purposes. or bathing much in muddy water be avoided. for Barlo w . water heated to 50 oC or treated with sodium bisulphate was safe. the disease may be prevented. Further. This approach was only partially successful. and it is certainly greatly to be hoped that the authorities will immediately adopt measures to save our troops from so formidable and painful a disease as haematuria. it was now clear that large bodies of wate r rather than transient pools should be avoided. Concerning control of infection in the country as a whole. for this is the only way in which the latter becomes populated with dangerous germs. that filtration through sand was untrustworthy. Looss was correct when he said: Infected persons should never evacuate urine or faeces into water.. he noted that practically all the water in Egypt came from the Nile. When Leiper worked out the life cycle of schistosomiasis in 1915. but hardly applicable to the indigenous populatio n living along the banks of the Nile and in similar endemic areas. The Mediterranean troops have. with the result that 50% of the snails survived 25.and that control of transmission based on the essential focality of transmission in many areas (St.for example. An alternative approach was to kil l the snails with chemical molluscicides. snail eggs were killed by these physical measures. and toxicity of the molluscicides for aquatic fauna 20. Nevertheless. 178 Control based upon mass chemotherapy lay in the doldrums for man y years. But on the contrary. largely because of the grea t expense involved. it was concluded i n 1962 that this approach had been unfruitful.Schistosomiasis haematobia 221 showed in field experiments that when the waterways were dried. the pyo. In 1933. Secondly. all these serious complications of Egyptian schistosomiasis have greatly diminished in number. with Webbe writing in 1981: There is ample evidence that area-wide mollusciciding is now successfully controlling snails in major control programmes . Bayluscide) 96. Humphreys reported that carbolic acid in a strength of 1 in 20.200 A third technique of control is by the mass treatment of infected persons.and hydronephroses. the difficulty in providing adequate teams to distribute the molluscicides. a large number of treatment centres w ere set up in an effort to control the infection but less than 5% of the total number of infected persons wer e treated each year. in Egypt and China .000 killed all the snails in the irrigation system in the Gezira region of the Sudan 112. More recently.. the numerous urinary calculi. no doubt exists that. These molluscicides were in tur n followed in 1957 by sodium pentachlorophenate 130 then in 1959 by niclosamide (Bayer 73.98. In 1941. In 1920. Chandler showed in labora tory experiments that snails were killed by immersion in a 1 in 1.the grave cases of urinary fistulae.. Nevertheless. more effective and less toxic drugs have appeared.000 solution of copper sulphate 46. 52 In Egypt. Recently the outlook has changed because of two factors.000.. Lucia. No influence on the mere occurrence of the disease has been obtained by the present methods. it has been realize d . Ghana. but copper sulphate remained the mainstay of intervention. In 1932.. Yemen and Saudi Arabia) is also being successfully prosecuted by killing snails and surveillance.My own view is that there is more hope of successfully dealing with the schistosomiasis problem by the symptomatic treatment of individual cases wherever they are met than by attempting to eliminate the disease by destruction of snails which can only be a practicable proposition in limited areas. Mozle y indicated that malachite green (mineralized basic copper sulphate) was just as effective and much less expensive 165. Christopherson himself wrote: It is in mass treatment in schools and villages where the hope to eradicating the disease lies. the Bulinus snails took up a position with the shell-opening facing down and secreted a protective coat of slime. then Khalil in 1927 demonstrated in a field experiment that all the Bulinus in an oasis were killed by this measure and that none were alive six months later 121.. a mood of optimism has returned. Rose reviewed the effectiveness of this programme and wrote: complete unanimity exists among all Egyptian specialists. This was hailed with enthusiasm following the introduction of specifi c treatment with tartar emetic in 1918.. Firstly. aestivation (similar to hibernation) of the snails. ALLEN JF. sis: 1946 10. Indian Journal of Medical Research 10: 482-491. Changing patterns of schistosomiasis in Egypt 1939-1975. Lancet ii: 375-376. 1893 16. Parasitic haematuria. even th e most optimistic must doubt that these techniques are likely to control. Bilharziosis and how to prevent it. ALBARRAN J. contribution à l'étude de la pathologie du cancer. ALLEN JF. Another approach was to attempt to improve sanitation. Bilharzia haematobia and circumcision. or bloody urine. 20. although the efficacy of the latter is yet to be proven. British Medical Journal ii: 1264. Notes on the genera Bullinus and Physa in the Mediterranean Basin (Mollusca Pulmonata). the problem of schistosomiasis seems unlikely to go away unti l socio-economic conditions improve to such an extent that provision of saf e water supplies and constant usage of reliable waste disposal systems become the norm in endemic areas. British Medical Journal i: 916. A major project was undertaken by the Rockefeller Foundation and the Egyptian government between 1928 and 1937 in which bore-hole latrines were introduced to rural houses. 1979 2. BERNARD L. ANONYMOUS. BLAIR DM. Lancet i: 660-661. Medical History 20: 176-188. Nevertheless. A newly differentiated parasite. Freshwater snails from Mesopotamia. and it is these people who are at most risk of developing disease and who make the greatest contribution to th e contamination of the environment with miracidia. This has led to th e introduction of "targeted mass treatment" in which only the heavily infecte d persons are treated. Sur un cas de tumeur épithéliale due à la Bilharzia haematobia. Lancet i: 249-250. Lancet ii: 640-641. ANONYMOUS. 1888 7. ZAKARIA S. ANONYMOUS. Lancet i: 1317-1320. it has the twofold aim of curing diseased persons and of reducing transmission . Lancet ii: 242-244. 1884 14. Although the prospects of control by immunization have been touted 22. 1897 4. a small number of person s harbour a large number of worms. the best results are obtained when there is integration of chemotherapy. ANNANDALE N. 1909 8. Endemic haematuria in Egypt. 1910 9. ANONYMOUS. ALLEN JF. Practitioner 40: 310-320. ALLEN JF. ANONYMOUS. 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Landmarks in schistosomiasis haematobia ___________________________________________________________________ 1851 1852 1852 Bilharz discovered adult worms Bilharz and Griesinger identified urinary lesions Bilharz diagnosed urinary schistosomiasis in a living patient by finding eggs in the urine 1866 Rubidge suggested on clinical and epidemiological grounds that infection was acquired by bathing in certain rivers 1889 Harrison suggested a relationship between vesical schistosomiasis and bladder cancer 1915 Leiper discovered that certain species of snails were chemotactic for S.Schistosomiasis haematobia 231 Table 8. haematobium miracidia. mansoni 1917 Diamantis reported the value of emetine in treatment 1918 Christopherson reported the efficacy of tartar emetic 1944 Barlow produced a patent infection in himself after placing cercariae on his skin 1940's Kikuth and Gönnert showed that miracil D had schistosomicidal activity in experimentally infected animals 1947 Blair. Kebrun and Dierich reported that metrifonate was effective 1964 Lambert and Ferreira reported that niridazole was active 1969 Clarke. haematobium and S. Blair and Weber showed that hycanthone was effective 1977 Various investigators reported that praziquantel was effective against schistosomes in experimental animals 1979 Davis. observed development of the parasite through the sporocyst to the cercarial stage in these molluscs. and produced patent infections in rodents and monkeys with cercariae derived from naturally infected snails that were collected in an area heavily endemic for schistosomiasis 1916 Leiper confirmed the differentiation of S. Biles and Ulrich reported that praziquantel was effective in humans __________________________________________________________________ .1. Hawking and Ross reported that miracil D was effective in humans 1962 Cerf. . hepatosplenomegaly. causes intestinal schistosomiasis or bilharziasis Major synonyms: Distoma haematobia. yellow-brown bodies rounded on both ends. compressed from all sides. Schistosoma haematobia Distribution: Africa. niridazole. oxamniquine. approximately similar to those eggs in size" 13. ar e biconvex with a sharp edge from which the conical appendage protrudes" 13. Theodor Bilharz found near S. his accompanying description leaves little doubt that the bodies he was seeing were remnants of S.Chapter 9 Schistosoma mansoni and SCHISTOSOMIASI S MANSONI SYNOPSIS Common name: intestinal blood fluke. haematobium eggs in calcified areas of a liver "strange bodies provided with spines. he found the same structures in a portion o f dysenteric large intestine removed from t he body of a boy who also had vesical schistosomiasis and had died from meningi tis. dysentery and hepatosplenomegaly in early. directed obliquely toward the pointed end. mansoni ova. No content was recognizable in these strange bodies. praziquantel ATTEMPTS TO DIFFERENTIATE SCHISTOSOMA MANSONI FROM S. mansoni eggs: "These bodies. HAEMATOBIUM In 1851. Caribbean islands Life cycle: Similar to S. They were scattered through the mucosa and submucosa as well as being embedded in bloody mucus on th e surface of the mucosa. Although the illustration he provided is har dly recognizable as that of an S. heavy infections Diagnosis: demonstration of eggs in faeces. ascites and oesophageal varices in chronic. heavy infections. South America. 13 In March of the following year. rectal mucosa or liver biopsy Treatment: hycanthone. Bilharz's description of these bodies again indicates that these were S. 233 . soon after he had discovered the adult forms of S. monkeys) Major clinical features: rash followed by urticaria. haematobium except that the vectors belong to the genus Biomphalaria and eggs are excreted in the intestines Definitive hosts: humans (baboons. mansoni egg shell. near the more rounded end was a conical appendage. On one side. for he wrote: They seemed to me to be long. haematobium and had seen their ova with the charact eristic terminal spines. Wilhel m Griesinger found the same bodies in a piece of large bowel. mansoni miracidia. but later abandoned this thesis in favour of the postulate that one f orm of egg developed into a male worm while . A few days later. Bilharz included a drawing of a "capsule" which is clearly the shell of a lateral-spined S.13 Proof that the bodies which occ upied Bilharz's mind were indeed egg shells of S. for in the legend accompanying an illustration in his paper of a typical S. mansoni was. provided in 1853. This naturally led Bilharz to put th e question: "Therefore. in retrospect. mansoni egg. I not only found them intermixed with eggs of Distomum haematobium in the calcified areas within the liver. the posterior of which contained the usual egg. in any case. but also. but on thi s occasion. It was in the front part of the oviduct. Sonsino then suggested that schistosomiasis was caused by two different species of worms. and mor e importantly. Secondly.13 Since he had seen this phenomenon only once. I made a drawing of that specimen at that time. since such a body was once found in the fallopian tube of the organism. he surmised that the specimen in the oviduct had metamorphosed abnormally early. Firstly. and in the mucosa of the large intestine in acute dysentery. There were two reasons for this. In a letter to von Siebol d dated 4 January of that year. he wrote: saclike bodies provided with a lateral spike (eggs? pupal coverings?). Are they a second type of egg or a kind of pupal covering assumed by the organism after leaving the egg?"13 As discussed in chapter 8. in the submucosa. This erroneou s observation was to set the scene for confus ion and controversy for the next half century as to whether there were one or two species of schistosomes tha t infected humans in Egypt. left no doubt as to his views: That these shells belong to the developmental stages of Distomum haematobium and not to another organism seems indubitable to me. each producing characteristic ova which differed in the position of their spine. Bilharz. however. haematobium eggs and these bodies intermingled in the tissues. haematobium: Last summer I found one of these bodies in one of the first female specimens of Distomum haematobium that I studied. he found S. although only once. Griesinger accepted Bilharz's contention completely. Bilharz's colleague. Bilharz believed that he had seen the same structure within a n adult female S.234 A History of Human Helminthology These structures were empty apart from a few granules massed against th e inner edge. resembling S. belonging to the developmental cycle of the Distoma haematobium. in forthright terms. Bilharz came down in favour of the latte r proposition. in the oviduct of a female worm which also contained ordinary eggs. they contained living o rganisms which crawled out and swam about. mansoni ovum12. Harley in 1864 was so struck by the complete absence of lateral-spined ova in the urine of patients with endemic haematuria in South Africa that he was induced to name the parasite in tha t region Distoma capense 44. 43 As mentioned in the previous chapter. how should we regard these bodies. but instead found schistosome ova. both conditions wer e attributed to infection with S. in 1882. whereas schistosomiasis in Egypt was hopelessly intermingled with urinary and intestinal pathology and eggs with terminal or lateral spines. Microscopical examination of the urine disclosed no ova.Schistosomiasis mansoni 235 the other became a female schistosome. however. demonstrated to the Royal Medical and Chirurgical Society in London microscopical sections of vegetations from the large bowel of an Arab who had suffered from dysentery and noted that "as is usual when occurring in this situation. but here its situation was terminal and not lateral" 124. Even so. who wrote: in my own experience the ova found in the rectum have in nearly all cases the spike placed laterally differing from those generally found in the urine. surgeon to the British consulate and Dea conesses' Hospital in Alexandria. Patrick Manson in England reported that a 38 year old British patient of his had contracted the infection in the West Indies where he had lived for 15 ye ars. In 1902. He also exhibited sections from the bladder of another patient and remarked that "each ovum was provided with a spine. and since he looked anaemic. In the following year. depositing its eggs in the rectum only. as so often happens in bilharzia ova from the alimentary canal. it was believed that schistosomiasis was restricted to Africa and adjacent regions. 82 Impetus to the idea that there may be more than one species of schistosome infecting humans was given by the discovery of S. which have the spike at the extremity. japonicum by Katsurada in . Furthermore. the other haunting bladder or rectum indifferently. he put forward the suggestion that: possibly there are two species of Bilharzia. and patients with intestinal eggs with lateral spines as shown b y Manson. In fact. It gradually became clear to invest igators in Egypt that different types of egg were associated with different dise ases. there were now cases on record exemplifying the two poles of the spectrum patients with urinary schistosomiasis and terminal-spined eggs as describe d by Harley. one with its lateral-spined ova. however. Zancarol's views were supported in the same year by James Mackie . however. fo r when he presented 13 cases to the Royal Medical and Chirurgical Society in 1885. Manson examined his stool s expecting to find hookworm eggs. he remarked that "In this ca se. For many years. Dr Zancarol. Manson in this paper made no great play about the egg s having a lateral spine. Thus. he was concerned to suggest that a mollusc or arthropod common to both African and American regions might be the long sought for intermediate host. The patient complained of vague aches and pains. he attributed no pathological or clinical significan ce to the remarkable variations in the appearance of schistosome eggs 19. a surgeon at the Greek Hospital in Alexandria. (the ova) were each provided with a large lateral spine" 124. haematobium. rather. Thus.78 Spencer Cobbold was not convinced. the spine is placed laterally" 81. Looss castigated Sambon's credentials saying: Among scientific workers. he proposed at a meeting of the Zoological Society of London on 19 March 1907 that the worm producing lateral-spined eggs b e named Schistosomum mansoni 102. He introduced his paper by remarking that: if Dr.. Putting al l these thoughts together. th e new Trematode is dedicated to him"103. straight spine at their posterior extremity. mansoni has a wide distribution throughout Africa.. Sambon's new species met with a vitriolic blast from Looss in a 39 pag e paper entitled "What is Schistosomum mansoni Sambon 1907?". variations in the clinical manifestations... he insisted that the differentiation of species could only be made on the morphology of the adult worms. japonicum. 73 He then launched into an attack on Sambon's propositions.. Sambon's view were correct. remarking on this occasion that although adult schistosomes of humans an d cattle were very similar in general appearance...S. curved. were. Manson's view was then championed by Louis Sambon. all of us who have devoted attention to the subject. with Looss amongst them. Sambon justified his creation of a new species on the grounds of difference s in the morphology of the eggs. it is not customary among scientists to assert something then call for the help of others to establish it..236 A History of Human Helminthology Japan in 1904 (see chapter 10).both of which he was destined to lose.It is found also in the West Indies. fiftyseven years ago. 103 Sambon reiterated these points later in the year in a further communication .. To further support his argument. one of his many genial intuitions. he had no doubt that a minute comparative anatomical study of these worms would bring out info rmation about many structural differences 104..and very likely in other places within the Tropics. lateral spine which distinguishes them from those of the old classic species with a short. Looss's arguments were centred on the following b ases. some of them. yet endemic haematuria was completely unknown 47. it is a good custom that anyone who believes he has made a new discovery also takes the trouble to prove it. a lecturer at the London School of Tropical Medicine.. mansoni ova are eliminated solely by way of the intestine...the direct infection hypothesis and the single species stance . but they never present haematuria.73 And indeed. He so named the parasite in recognition of Manson's earlier suggestion that there may be two species of Africa n schistosomes: "In appreciation of this.S. Afte r bemoaning the fact that no notice had been taken of the (vague an d unspecified) cautionary "hints" that he had "dropped" while in London tw o years earlier (but precisely to wh om he could not remember). Sambon drew attention to the report in July of that year by Holcomb of a large number of cases of schistosomiasis wit h lateral-spined eggs in the Caribbean. including no less than 167 cases i n Puerto Rico. would have indeed been wandering in the dark since the time of Bilharz himself. Firstly. not on . Looss was th e arch protagonist of two controversial theories . and dissimilar geographical distributions o f infection: the ova of the new species have a large..The patients harbouring this parasite suffer from a haemorrhagic enteritis.. with the exception of the male S. Dr. mansoni. and that thes e lonely worms sometimes migrated as far as the large intestine. "violent" and "ill-considered" paper at once. to let it be absolutely clear where h e stood. The foun dation stone of Looss's faith was Bilharz's statement that he saw both types of eggs in one worm. He postulated that when the infecting dose of miracidia was high. Sambon will explain it by his theory.. I wonder how Dr. Looss contended feebly that the differences i n geographical distribution of the two forms of parasite and disease cited b y Sambon were based "upon a peculiarly one-sided interpretation of th e literature" 73. Looss dismissed the differing clinical and pathological pictures associated with the two forms o f eggs on the basis of variations in the habits of the human host and th e conditions of the country. Moreover .. He produced an amazing and intricate hypothesi s based upon the supposition that mirac idia were infective directly.. Sambon if he had studied of those authors who he accuses of having failed to recognise an obvious fact.73 Looss then remarked that if his memory did not fail him.that this species. and regretted that h e could not produce them. Sambon wishes to maintain that there is an independent "Sch. Nevertheless.... therefore. Since this had not yet been done. he now found it necessary t o .. Secondly. Looss concluded his lengthy paper: there is no possible doubt. Looss deduced that lateral-spine d eggs were abnormal and were probably produced by unfertilized femal e worms. but he had delayed in the hope that someon e would be able to describe distinctive morphological features for adul t S.. Looss believed that there was not a sharp line of demarcation between these two responses. mansoni". Sambon replied to Looss' s criticisms in a long article with the same title as that used by Looss 105.. and that they developed into sporocysts in the liver. h e suggested that when the infecting dose was low.If. haematobium..73 In January of the following year (1909). Finally. He then adde d sarcastically: This observation is now fifty seven years old and might have been known to Dr..the entire proof of its existence remains to be given..Schistosomiasis mansoni 237 the appearance of the eggs. he reiterated: The occurrence of terminal-spined and lateral-spined eggs in one and the same individual worm is one of the fundamental facts on which my views rest. there would be plenty of male worms present to carry the females off to the vesical venous plexus where they produce d terminal-spined eggs and caused urinary schistosomiasis. solitary females sometime s developed. he had seen several similar female worms during the course of the years.must produce the same two shapes of eggs as does the Sch. He explained the presence of a miracidium in some of these eggs as being the result of a process of parthenogenesi s. that these spinsters produced lateral-spined eggs. He began by saying that he ought to have refuted Looss's "critical". Extrapolating from his observations on a number of trematodes.73 Looss thought that the position of the spine depended upon the position of the egg during the process of its formation in the ootype. In contrast. quoted precedents established by zoologists. Sambon declared: Until he can show me an actual specimen I am bound to place the worm capable of producing the two kinds of eggs with the phoenix. Sambon showed that he had not distorted the literature. haematobium. 105 Two years later (1911). an d theories often require a careful selection of the facts" 105. Next. mansoni and S. Finally. Conce rning Bilharz's alleged discovery and Looss's vague confirmation of two forms of egg within the one adult worm. slavish submission to authority i s another"105. and do. rather. Further. Looss returned to the debate. He noted that large numbers of patients in certain region s passed vast numbers of lateral-spined eggs. yet not a single terminal-spine d ovum could be found. Sambon then proceeded to counter Looss's arguments point b y point.238 A History of Human Helminthology reply lest his silence be interpre ted wrongly. and there was no doubt that urinary schistosomiasis alone occurred in southern Africa. haematobium can. had acquire d their infection in Africa. He insisted that the marked differences in the morphology of the eggs were quite sufficient to estab lish a new species. he stood his ground and declared: I never for a moment placed myself on the same level in the latter respects (as a helminthologist) with the celebrated professor of Cairo.105 He then demolished Looss's dismissal of the different clinico-pathologica l effects associated with the two forms of worms. but at the same time I would say that I have paid some attention to the subject. he reasoned that explaining all these lateral spines on the basis of abnormality an d parthenogenesis bordered on absurdity. He had concluded on the basis of further observations that it was not necessary to invoke parthenogenesis. He had th e impression that once the production of normal (terminal-spined) eggs ha d begun. bu t reiterated: "that the females of S. but tempered this by remarking that : "Respect for authority is one thing. Sambon let it be clear that he had the utmost regard for the eminent scientist who had studied helminthology in Egypt during the previous 25 years. it was likely that the several patients wit h urinary schistosomiasis in America that Looss had referred to. even now" 74. there is a "transitio n period" following which the eggs become terminally spined. and asserted that Looss himself had subscribed to new species on much flimsier grounds. and cannot abandon my independence of judgement.there would have to be an entire absence of ma le schistosomes. the others (lateral-spined) were usually evacuated quickly. Sambon then re-emphasized the different geographical distributions of S. Instead. . and that after fertilization. demonstrating that Looss' s views were a: "multitude of surmises and conjectures more or les s improbable"105 and adding nastily: "But Professor Looss has a theory. and questioned how this could possibly be consisten t with Looss's idea that they were a product of unfertilized female worms . stung by Sa mbon's objections. he postulated that unfertilized eggs are laterally spined. the chimaera and other mythical monsters. produce two forms of eggs is beyond question. or my right to give expression to my views. Looss tried to ridicule da Silva by claiming that the ova that h e described were nothing more than concretions. Also in 1908.74 Moreover. Pirajá da Silva in Brazil recovered 24 worms. He first published these opinions in Portuguese in 190892. I mean they require more facts. who was an assistant in internal medicine at the Santa Isabel Hospital in Bahia. Looss replied that each and every one of these features could be seen in in Egypt. Pirajá da Silva. in 19 07 examined material from patients in Puerto Rico and thought that the male worms were more brown in colour and had a larger ventral sucker 47. Pirajá da Silva received the full force of Looss's wrat h when he wrote vitriolically: Thus Pirajá da Silva's 'proof' of the existence of a 'second species' of Schistosomum becomes reduced to a combination of several very elementary mistakes. To all of this. at that stage. These included differences in the outlines of the anterior end of the male worm and the posterior end of female schistosomes. a more distal location of the caecum. Leiper lea ned towards Looss's unitarian view. Leiper studied material from Uganda and thought that ther e were differences in the shape of the testes 69. Holcomb. an assistant surgeon with the US Navy. what the conclusions based on such evidence are worth scientifically. a number of workers. Pirajá da Silva presented his findings to the German Society of Tropical Medicine i n . particularly in th e Americas. In April 1912. before they write on parasitological questions. every reader is at liberty to decide for himself. Both forms occur in Egypt and we in Europe get the worms from the portal veins and these may be one or the other of the two forms and so far we know no way of differentiating them. and subtle differences in the structure of the female reproducti ve organs when compared with Looss's figures of S. for he went on to say: There is a good deal too much theory alike in Looss' as in Sambon's position. had embarked upon a search for characteristic morphologica l features of worms producing lateral-spined eggs which would allow definite distinction of S. should make themselves acquainted with the parasites they deal with. although in a letter to Pirajá d a Silva in February 1909 he wrote: I regret that so far I have not been able to separate the Schistosomum haematobium from the Sch. 70 In fact. 70 Similarly. then amplified them in English 93 and in French 94 in the following year.Schistosomiasis mansoni 239 While all this was going on. haematobium. described a number of features of the adult worms which he thought were distinctive. from the portal venous system of a single cadaver. haematobium. all these worms produced only lateral-spined eggs. I studied for a year under Professor Looss and saw enough of his work to feel more reliance on his observations than on those of Dr. Flu (1911) thought that there were differences in the formation of the anterior part of the gynaecophoric canal of the two parasites 36. In the following year (1908). mansoni in the specimens I have received from abroad and I cannot therefore send you types of each. But am I to be blamed if I urge that authors. mansoni from S. Sambon but I have not yet made up my mind finally on the subject. less salien t spinous papillae. including both sexes. mansoni in Puerto Rico before Pirajá da Silva.95 It is with these last remarks that Pirajá da Silva probably put his finger on the deficiency in Looss's armamentarium that prevented him from seeing the truth. it was this achievement which enabled him to differentiate definitively between S. bilharziasis is a disease affecting exclusively the lower portion of the intestines. Both Sambon and Pirajá da Silva were physicians and were impressed by the marked pathological. there was no doubt in their minds that there were tw o species of schistosomes. was not a clinician an d failed utterly to appreciate th e completely different responses of humans to the two species of parasites. clinical and diagnostic differences between urinary and intestinal schistosomiasis.. although he had never seen my slides. Gentlemen: I am not a zoologist but I have for many years dealt exclusively with helminths. mansoni adult worms in Brazil. The events that led up to this discovery have bee n described in chapter 8.. haematobium. A wrong interpretation of the microscopic aspect of my slides might have occurred. and it remained for Leiper in his studies of the life cycle of schistosomes to prove beyond all doubt that the two species were separate.. mansoni and S. mansoni adults in Africa. Furthermore. extending into the liver. although they did not recognize them as such. MANSONI By the middle of 1915. whether due to one or two species. Looss: the eggs I observed in the uterus of the female Schistosoma were considered by him as mere concretions. I based myself on my own observations. being a physician. de Cerqueira Falção ha s ignored the fact that Holcomb e had described adult S. incontestable discoverer of 'Schistosoma mansoni'" 18.In Bahia. But returning to Pirajá da Silva in Hamburg: "Pirajá faced with courage and firmness the giant Looss stating. Parenthetically. on the other hand.Our best clinicians are unable to report on any bladder affection as being due to Schistosoma. However.'I was afterwards contested with energy by Prof. I have now the pleasure to emphasize that in the course of careful and repeated investigations on some 100 cases of bilharziasis in Bahia. Looss. was transmitted by the mediation of certain snail intermediate hosts. . I could never find one single egg bearing a terminal spine.. Thus.. and that many observers had doubtless seen S.240 A History of Human Helminthology Hamburg. When put together with the variations in th e morphology of the eggs and in the geographical distributions of the two forms of schistosomiasis. an impasse was reached. it ought to be re marked that while it is true that Pirajá da Silva did discover S. The subsequent discussion has been published by de Cerquier a Falção who has championed da Silva's cause in a paper entitled "Professo r Pirajá da Silva. in spite of Looss's authority. Leiper was convinced that schistosomiasis in Egypt... I am not ready to admit such a mistake to have been made. ELUCIDATION OF THE MODE OF TRANSMISSION: DISCOVERY OF THE LARVAL STAGES AND THE SNAIL INTERMEDIAT E HOST AND PROOF OF THE EXISTENCE OF S... He published his findings and conclusions in a preliminary report in the British Medical Journal in March 1916: By submitting individual mice. also infected with cercariae from P. Secondly. haematobium. in rats infected with P. they indicated that the adult worm was S. each on one occasion only. This mouse was infected with adult schistosomes. Two monkeys taken from London to Egypt were infected orall y on the same day. the infection was so light that no worms were found in any of these animals. Similarly. another group of animals had to be infected heavily with cercariae from Bulinus in order to establish the specific nature of this form of parasite. a mouse which had been infected with cercariae from Planorbis boissyi (now known as Biomphalaria alexandrina) died. whereas according to Sambon. but they died within a fortnight from an overwhelmingly intense infection . for a limited period to infection with the cercariae from single infected molluscs. he found that four monkeys. Egg production began during the ninth week. Accordingly. mansoni. Leiper reviewed the position and realized that h e needed to infect animals lightly with cercariae from P. he returned to Egypt in November 1915 and infected monkeys orally and mice. Meanwhile. boissyi-derived cercariae. According to Looss's later theory. rats and monkeys percutaneously. The smaller animals were killed weekly in order to assess the mode of development. they were all laterally spined. one with cercariae from Planorbis and the other with cercariae from Bulinus. it has been possible to demonstrate that those developing in the Bullinus molluscs always produce bilharzia worms which give rise solely to terminal-spined eggs. only laterall y spined eggs were found.Schistosomiasis mansoni 241 Shortly before Leiper left Egypt for Europe in July 1915. Unfortunately.71 He then turned his attention to experiments with monkeys. they showed differences in the structure of the gut when compared with with those obtained from mice infected with P. Leiper had also infected some animals very lightl y with cercariae from Bulinus (known to Leiper as Bullinus) snails in the hope that some of these animals would live long enough to permit the testing o f potential anthelmintics. Worms were first recovered 17 days afte r infection from a mouse infected with cercariae obtained from Bulinus. they were abnormal products in the transitional phase of young sexually matu re worms of S. and although only two or three eggs were seen. worms were found in the liver and in th e mesenteric veins but no eggs were seen. although the parasites were immatur e. a third monkey had been . The former monkey began to pass lateral-spined eggs after six weeks and died from dysentery on the sixtieth day. also began to pass lateral-spined eggs in August. In October of that year. The other monkey had no eggs in the urine or faeces and was killed six weeks after infection. while those which have developed in Planorbis boissyi always become worms which produce solely lateral-spined eggs. boissyi. boissyi-derived cercariae. On Leiper's reaching London. boissyi so that they would survive for several months and thus enable the female schistosomes to pass through Looss's hypothetica l "transition period". Leiper concluded that: The terminal-spined and lateral-spined eggs found in bilharzial infections are. mansoni. at one stroke. Confusingly. Leiper confirmed the differentiation of Egyptia n Schistosoma into two species. He explained the restriction of infection to the intestine in monkeys as being due to differences in the venous connections of th e bladder in this host. Porter showed in 1920 that in southern Africa that Planorbis pfeifferi (= Biomphalaria pfeifferi ) was a vector of S. tenagrophilus. although development also took place but to a lesser extent in P. two Sout h Americans working independently confirmed his findings with respect to S. They confirmed Leiper's findings by infecting monkeys with cercariae fro m Planorbis snails then subsequently recovering adult S. Adolpho Lutz reported that certain species o f local Planorbis snails were intermediate hosts of S. there was no difficulty in the names of S. mansoni in Brazil. mansoni standing for the worms causing urinary and intestinal schistosomiasis. Shortly afterwards. Leiper had determined that cercariae derived from Planorbis produced only terminal-spined eggs. mansoni. and are spread by different intermediary hosts. no eggs were found in the urine or bladder.242 A History of Human Helminthology infected orally with cercariae from Bulinus. mansoni. In order to cl inch the matter completely. the normal and characteristic products of two distinct species. mansoni 97. it began to pas s terminal-spined eggs in the faeces after 12 weeks and died five weeks later. bahiensis (now known as Biomphalaria glabrata ) was the species most susceptible to infection with miracidia obtained from laterally spined ova . well past Looss's transition period. In December 1916. respectively 72. he completed the cycle o f development by infecting guinea pigs and rabbits with cercariae from thes e . therefore. ferrugineus and P. At this point. He experimented with five species of Planorbis and found that P. B. but was unable to identify whether it was S.72 Thus. rats and monkeys were infected lightly with P. i. and at the same time demonstrated that Bulinus species were the intermediate hosts of the former worm and Planorbis boissyi (Biomphalaria alexandrina ) was the vector of the latter schistosome. Within a year or two of the publication of Leiper's discoveries. mansoni miracidia. olivaceus = P. boissyi cercariae and kept alive for nine months. They infected Planorbis molluscs with S. Cercariae developed after five weeks or so in the same manner as Leiper had described. In the following year. Leiper went on to remark that he ha d examined the only remaining fragment of a male schistosome found in 1857 by Cobbold who had called it B. and confirmed that Bulinus species were resistant to that para site83. haematobium and S. mansoni. Manson-Bahr and Fairley studied intestina l schistosomiasis in British Em pire troops of the Egyptian Expeditionary Force. at autopsy. magna. Consequently.e. mansoni. Following this. haematobium and S. haematobium and B. haematobium or S. S. but he observed that the rate was dependent upon the temperature 75. lateral-spined eggs only were produced during that time. producing altogether about 100. 1931. however.Schistosomiasis mansoni 243 snails then subsequently recovering S. Afroplanorbis of Thiele. Mature cercariae were found about fiv e weeks after exposure 77. With respect to development of the parasite in the snails. by Pirajá da Silva as early as 1912 when the latte r described them and named them Cercaria Blanchardi. th e most usual site of attack being the antenna. mansoni miracidia then produced patent infec tions in a variety of experimental animals. guadelupensis (now known as Biomphalaria glabrata ) with miracidia obtained from S. Lutz showed that P. Brazil 16. In Caracas. Biomphalaria raised by Preston in 1910 98.000 cercariae from a single miracidium 31. Sporocysts were apparent within three to four days then secondary sporocysts were seen migrating into th e visceral sac 20 days after infection. White mice. The taxonomy of the snail vectors of S. mansoni cercariae. Finally. mansoni ova51. depending upon the season and continued to be discharged for four months . however. Ampullaria luteostoma and P. He then found many naturally infected snails of this species in the city. Tropicorbis enunciated by Pilsbry and Brown in 1914. A number of other genera were raised. noted that it had long been recognized that the known species of snails which serve a s . He found that miracidia penetrated the molluscs within 10-15 minutes. cultratus were infected under laboratory conditions. Also from South America. Planorbis boissyi described by Potiez and Michaud in 1838 was shown to be identical with Planorbis alexandrinus described by Ehrenberg in 1831. mansoni had in fact been seen. they first identified sporocysts on the eighth day. mansoni were recovered from the portal vein of two mice. Finally. to house intermediate hosts of S. guadelupensis containing large numbers o f cercariae. Juan Iturbe (1917) infected P. Iturbe found. Venezuela.32. guinea pigs and newborn puppies were infected percutaneously with these cercariae. that th e most constant success was obtai ned when experimental animals were fed food contaminated with livers of P. in addition to the genus Planorbis described by Geoffoy in 1767. these included. Cercariae began to emerge after 24-35 days . The cycle of transmission was again invest igated by Faust and his colleagues in the early 1930's. mansoni. olivaceus was infected naturally with S. He observed the transformation of miracidia into sporocysts then th e production of secondary sporocysts then the appearance of cercariae after six to seven weeks. mansoni has been a matter of some controversy. however. A World Health Organiz ation study group in 1954. and Australorbis erected by Pilsbry in 1934. adult S. Lutz also pointed out that the cercariae of S. this latter name therefore had priority. but he did not regard these as being vectors in nature. Cardoso in 1923 reported that Planorbis centrimetralis was the common intermediate host of the parasite in Sergip e State. two months later. mansoni adult worms 76. They infected the snail they called Heliosoma (Planorbina) guadaloupense (= Biomphalaria glabrata ) with S. and re-examined in detail the kinetics of inf ection in experimentally infected snails. but no t recognized as such. pfeifferi. nigricans. They noted that schistosomula had left the skin within 16-20 hours of infection. Larvae were found in the . Fairley then went on to describe the mechanism of egg-laying by female worms in the distal tributaries of the portal venous system. guadaloupensis. mansoni are generically the same. mansoni. and that they al l have probably been derived from the same stock. A few years later. mansoni through the tissues of experimental animals and found that the event s were similar to those that had already been described for S. As already noted. mansoni 99. therefore the correct name for the major South American vector o f schistosomiasis mansoni is Biomphalaria glabrata . Armigerus. Planorbina and Taphius. they were discovered within the hepatic radicles of the portal vein where they were believed to feed for the first time. P. Iturbe and Gonzalez in Venezuela studied the migration of S. Fairley repor ted his observations in monkeys infected with S. P. Male worms were found in the portal veins 18 days after infection. MIGRATION OF WORMS IN THE DEFINITIVE HOST In 1919.244 A History of Human Helminthology intermediate hosts for S. olivaceus and perhaps P. P. In an annotation on an abstract concerning this decision. In the same year. Wright noted that it had not been necessary to consider Australorbis and Tropicorbis since they were both junior synonyms of Biomphalaria 123. rabbi ts and monkeys infected experimentally with a Puerto Rican strain of S. and on the fourth day. and pas sed mainly via the veins but partly through the lymphatics to the lung capillaries where they were first seen at 20 hours. then the resultant schistosomula passed via the bloodstream through the hea rt and lungs to the liver. They recommended that the name Biomphalaria should be used for all the snail intermediate hosts o f S. the International Commission on Zoological Nomenclature confirmed this view and ruled that the correct generic name for th e following snail vectors of S. the proper name for Australorbis is Biomphalaria. immunis. Faust and his colleagues re-investigated the route an d kinetics of migration in rats. In 1965. this was the same as has already been recounted for S. mansoni. mansoni. was Biomphalaria 50. P. Concerning the South American molluscan vectors. He observed that the worms inhabited chiefly the inferior an d superior mesenteric veins and tributaries of the portal vein in the liver. By the third day. Martins in 193 8 considered that Planorbis centrimetralis . peregrinus were all synonyms given to members of a variable species properly known as Australorbis glabratus 85 . but female worms were not identified until one month after exposure 52. they had reached the systemic circulation. haematobium (see chapter 8). lost their tails in the process. They observed that cercariae penetrated the skin within fiv e minutes. The correct names for the major African vectors of schistosomiasis mansoni ar e therefore Biomphalaria alexandrina and B. japonicum ( see chapter 10). 33. however.. add a caveat: But I do consider it possible that. at least to the naked eye. He did.. but that "distomiasis of the larg e intestine. mansoni infection. Bilharz found clumps of eggs as well as eg g shells which he thought were S. in some cases... however. seem very similar to those of true dysentery. Bilharz and Griesinger performed an autopsy on a boy who had died fro m meningitis. One patient has been recorded who. it was markedly congested and covered with reddish mucus. despite the most assiduous searching . Epidemiological evidence . Mature worms were first seen in th e colonic venules 35-40 days after infection 32. Adult worms may live in the portal venous syst em of humans for many years. the mucosa was somewhat swollen and delicate. haematobium. inflamed areas were both more coarsely congested and almost or completely normal stretches of mucosa. suggests that the average life span for these worms is between five and ten years 120. he wondered whether these trematodes might not be the cause of both the acute and chronic diseases of the large intestine that abounded in E gypt. Against this.43 . Griesinger discovered eggs with lateral spines containing miracidia in dysenteric large intestine: In a black-pigmented large intestine showing scars of healed ulcerations and many warts and spines.Schistosomiasis mansoni 245 lungs up to 19 days after infection. I found (19 March 1852) an enormous number of Distoma shells (eggs?) (sic) provided with a lateral spine. was still passing eggs containing living miracidia 116. was the fact that during the short time that he had left in the country. haematobium "capsules" in this intestine . On 15 March 1852. Griesinger did not always find eggs in cases of dysentery.Between these hyperemic. although neither of these investigators realized that the pathological changes they saw in the large bowel were caused by S. Consequently. In addition to urinary sch istosomiasis. and peak numbers of worms in the live r were reached on the thirteenth day. Several days later. he reached the conclusion that most of the dysenteries aros e from causes other than schistosomiasis. but nevertheless a highly important complication o f these diseases" 43. at least 26 years after infection. disease of the intestinal tract was discovered: From the middle of the transverse colon to the anus. CORRELATION OF INFECTION WITH PATHOLOGY AND INVESTIGATIONS OF PATHOGENESIS The pathological changes in schistosomiasis mansoni were described b y Bilharz and Griesinger soon after the discovery of S. however.43 When Griesinger found a number of such patients. Distoma alone can effect changes in the large intestine which..13 As has been discussed earlier. I was fortunate enough to see massive hatching of the organisms. In the region of sigmoid colon and in the rectum were superficial erosions.. is only one. so that the cut surface of the liver looks as if a number of white clay-pipe stems had been thrust at various angles through the organ. longitudinal sections of the canals reveal elongated masses of similar appearance and thickness. Several years later. As his patient suffered from both urinary and intestina l schistosomiasis. Belleli described the histological characteristics of a tumour. the papillomata have necrosed and separated off at their pedicles. Thus. The most common lesion in the intestinal tract is the presence of papillomata of varying sizes and characters along the whole length of the intestine from the ileum to the anus.. In 1904. the liver presents a remarkable appearance due to an enormous increase of the fibrous tissue (Glisson's capsule) which normally surrounds the portal canals. Zancarol (1882) demonstrated that colonic vegetations. There is an enormous thickening of the walls of the gut. . it is not now possible to be certain whether Kartulis saw ova of S. whereas. often in considerable numbers... When a portal canal is cut transversely. removed from the rectum of a patient in Egypt. Thei r manifestations and the resulting complications were described by Maddern: The most common seat of infection is the lower part of the small intestine and the large intestine generally. a dense packing of its interior with papillomata. with hard bilharzial tissue.. This gave rise to speculation that irritation by parasites may play a part in tumour formation 3.. and a fixing of the intestine with massive deposits behind it and between the layers of its peritoneal attachments.. he had n oticed that the liver had an unusual appearance: On section.. and deposits of bilharza tissues in the appendices epiploicae and on the serous surface of the gut. the size of a small apple.A small blood vessel may often be seen running up to.. which in th e fresh state had the appearance of internal haemorrhoids. haematobium or both. certain lengths of the large intestine become infiltrated.. again. mansoni.from a sixth to a quarter of an inch.. but Ferguson was later to remark that the rarity of malignant neoplasia in intestinal schistosomiasis stood out in contrast with that seen in the urinary infection 34. 110 Microscopical examination of six of these livers revealed that this periportal firosis was associated with the presence of schistosome ova: Among this tissue are seen ova of the Bilharzia haematobia. William St.Sometimes.Over quite extensive areas of certain parts of the large intestine..246 A History of Human Helminthology These changes were then studied in more detail in histological sections . From time to time. the diameter of the mass being. together with their peritoneal attachments. S Kartulis in 1885 was the first person to report the deposition of eggs in the liver55. and widening into.. the mouths of the contained vessels and bile ducts are seen embedded in the centre of a circular or slightly oval area of white connective tissue. were in fact folds of mucous membrane which were stuffed wi th schistosome eggs 124. sometimes thickly scattered or again sparsely distributed throughout the mucous membrane. resulting in ulcers of dysenteric appearance. it had th e appearance of an ordinary ad enomatous polyp. .79 Although Bilharz originally found adult s chistosomes in the portal vein close to the liver. Clair Symmers published the results of his observations on liver pathology during a five year period in Cairo. These polyps were recognize d frequently in Egyptian schistosomiasis but rarely elsewhere. S... but groups of ova were seen in the connective tissues 8. will have to be considered" 4. If the numbers of eggs were small. 110 Although he entitled his paper "Note on a new form of liver cirrhosis due to the presence of the ova of Bilharzia haematobia". and had by its presence produced the proliferation of tissue which resulted in cirrhosis. Day and Ferguson reported thei r experience with this problem and concluded that it was not due t o schistosomiasis 23. He regarded splenomeg aly as an early and often transient feature of S. the view was promulgated that these features were very similar to Banti's syndrome and "before falling back on this obscure diagnosis in the future.It presents an absolutely different picture from the ordinary type of schistosomiasis mansoni. In 1909.17 Experimental studies. in 1959. Most of the eggs were dead with merely the shell remaining and were surrounded by fibrou s tissue. The paucity of eggs in the liver and the recovery of male worms alone from the portal vein. an attempt has been made to link the abdominal distension and gy naecomastia seen on several reliefs on the tomb of Mehou. Thus.. mansoni. an ovum. but concluded that progressive and lastin g splenomegaly may accompany hepatic schistosomiasis mansoni. Fifteen years later. There is very little or no alimentary disturbance or implication of the gut.. however.. Cirrhosis of the liver and splenomegaly with ascites have long bee n recognized as being frequent in Egypt. this form of liver disease accounted for 4% of the admissions to the medical wards of the Kasr-el-Aini Hospital in Cairo during the early part of this century. the brunt of the infection being inflicted upon the viscera. led Girges in his review to conclude that: Egyptian splenomegaly is a disabling endemic parasitic syndrome caused by male Schistosoma mansoni infestation of the liver and portal vein.. the dense periporta l (pipestem) fibrosis of Symmers was found 22. to hepatic involvement i n schistosomiasis 46. the genesis of these liver changes remained a matter o f controversy for many years. are still disputed.40 Subsequently. Carter and Shaldon wrote: the importance and extent of the infiltration of the liver by ova. eventually placed beyond any doubt tha t when splenomegaly and ascites were due to schistosomiasis of the liver.. a diffuse multilobular cirrhosis was established. the question of schistosomiasis. Indeed. even whe n infection of the intestinal tract was slight. and the nature and causes of the fibrosis found in the livers of patients with schistosomiasis. however. it is clear that he was visualizing eggs of S. they . for he remarked that most of the ova wer e laterally spined. a notable of the VIth Dynasty.Schistosomiasis mansoni 247 such a mass of concentrically arranged young fibrous tissue. Day changed his position when ova were discovered at liver biopsy in a series of patients subjected t o splenectomy. Nevertheless. Certainly. Symmers thought that all of these changes were indicative of a cirrhosis of the liver caused b y schistosome ova. Day believed that there were tw o types of "cirrhosis". and lying in the centre of the newly formed mass. but he occasionally observed fresh ova which were filled with a mass of inflammatory cells. however.. haematobium infection. but if they were numerous. as if it had become impacted in the vessel. whereas the rest were due to eggs. Griesinger's postulate that eggs might sometimes be carried in th e circulation to organs outside of the portal venous system was borne out when Belleli7 reported the finding by Mackie in 1885 of numerous small. Thus. It is now clear that in those instance s described by the early investigators in which cirrhosis was associated with a minimal number of eggs. showing that ova were at first surrounded b y fibroblasts and foreign body giant cells to form a granuloma which he called a "bilharzial pseudotubercle" 48. of that condition together wit h coincidental light schistosome infections.29. the great proportion of obstruction being generated by granulomas117. This was echoed by Koppisan who described the pseudotubercle as the fundamental histopathological unit o f . sometimes accompanied by endothelial thickening of the arterioles. Crucial to such a n understanding was the realization that the primary inflammatory reactio n around schistosome worms and eggs in the tissues was of a non-suppurative nature. Symmer s described the recovery of a pair of copulating worms from the left lung of a 35 year old person who had died from intestinal schistosomiasis 111. Hutchinson in 1928 detailed thi s phenomenon more clearly. In 1905. splenomegaly . Pulmonary schistosomiasis was then investigated intensively by Shaw and Ghareeb who examined 282 cadavers of persons with schistosomiasis mansoni an d schistosomiasis haematobia in Egypt and found that in 2%. it is apparent that schistosomiasis with heavy egg deposition and subsequent granulomatous inflammation may cause portal hypertension. death was du e directly to lung damage caused by these parasites. attempts wer e made to comprehend the genesis of these changes. one third of all these patients had schistosomal pulmonary emboli. Thus. infections with worms in the portal system but without eggs in the liver failed to induce significan t changes in the haemodynamics of the portal venous system in experimenta l animals. mansoni 26. in retrospect. Fairley in 1919 described "tubercles" containing many eosinophili c leucocytes around eggs in monkeys infected experimentally with S. Following delineation of the pathology of schistosomiasis. Further. The ova caused necrosis of the vessel walls and passed into the alveolar spaces an d were associated with a chronic inflammatory re action. resulting in cor pulmonale 107.248 A History of Human Helminthology were the result of presinusoidal hypertension caused by obstruction to blood flow as a result of granulomas around the eggs. ascites and oesophageal varices. Moreover. the patients had cirrhosis resulting from one of the many other causes. the eggs themselves were calculated to contribute less than 5% of the obstruction. 10% of these emboli were due to the adult worms themselves. as defined by liver parenchymal cell death. but a simple hepatic fibrosis. Progressive understanding of the genesis and evolution of these lesions led to a solidification of the concept that the condition described b y Symmers was not cirrhosis. nodular regeneration and sclerosis. fibrosing abscesses containing schistosome eggs in the lungs of a man who had die d from the complications of urinary schistosomiasis. known and unknown. haematobium and S. 119. cough. pain in the hypogastrium. Eventually. but between four weeks an d three months later. The incubation period was uncertain. a few years later. as in dysentery 79. myalgia. KS Warren and a number of other investigators showed that these granulomas were the consequence of cell-mediated immun e reactions to schistosome egg antigens 117. The patients wer e sometimes emaciated. and lasted for 12-48 hours. The early manifestations of infection w ere reported by Lawton in 1917. but that straining at stool resulted only in the passage of a little mucus and blood. fever. Girges reviewed the clinical aspects of schistosomiasis on the basis of his observations of 4. Whether or not resistance to reinfection is generated by prior exposure t o infection has been a vexed and controversial topic. there was a gradual onset of anorexia. rigors. mansoni infection at Tanta on the Nile . In 1922. Generalize d urticaria was always present. mansoni as a separate entity by Leiper in 1916. Examination revealed abdominal tenderness. sweats and abdominal pain. usually during the second and third week of the clinical illness. soon after the differentiation of S.Schistosomiasis mansoni 249 schistosomiasis mansoni. and a frequent desire to defaecate. tenesmus. He wrote that the most commo n lesions in the intestinal tract were papillomas in the large bowel associate d with symptoms ranging from minimal to diarrhoea. and passage of blood and mucus. concluded that these effects were more probably explained o n ecological grounds. Reductions in frequenc y and intensity of infection in older age groups have been put forward as a n indication of the acquisition of such resistance. partic ularly in the right upper quadrant and over the descending colon. as well a s enlargement of the liver and spleen 67. in his majo r review118. These features were reiterated by Maddern. but Warren. Diarrhoea was only an occasional and transitory feature. Several of the men had noticed itching when coming out of the water afte r bathing.000 cas es of S. RECOGNITION OF THE CLINICAL FEATURES The dysenteric symptoms of schistosomiasis were emphasized by Mackie in Alexandria in 1882. These symptoms had often been present for months. and rectal ex amination disclosed firm nodules about the size of a small bean in the rectal mucosa 78. particularly behavioural influences on contact wit h contaminated water. He noted that many Egyptians suffering from thi s condition complained of a feeling of a constant weight and discomfort about the rectum. headache. He also portrayed an evolutionary process in which an infiltration of eosinophils and neutrophils around ova in the tissues wa s followed by the appearance of ep ithelioid cells which were in turn replaced by fibrosis65. also in Egypt. Lawton described the clinical features of a group of 24 Australian soldiers who had been infected at a freshwater canal at Tel-el-Kebir during World War I. dizziness. often associated with malaise. Thi s frequently makes it difficult to discern which features are due to schisto somiasis and which are due to other pathogens.Girges considered it the terminal stage of infection with marke d sclerosis and contraction of the tissues and with only a few atrophie d papillomata left. As already indicated.this was seen in nearly three fifths of his patients and coincided with the ap pearance of eggs in the faeces and was characterized by exacerbations of dysentery every 15-20 days associated with fever. there was some . it was recognized that such an outcome was uncommon. (3) a late form with cirrhosis and splenomegaly 39. In many endemic areas. hepatosplenomegaly.2% of hi s patients . anorexia and cough.the intestinal and hepatic.this was seen in 3% of his patients and was marked by the sudden or insidious onset of fever. Ova were typically absen t from the stools. (4) final stage or "stage of repair" was seen in only 0. (3) intestinal or papillomatous stage . He divided them into two types . Luci a showed that gastrointestinal symptoms were no more frequent in infected than in non-infected individuals. Similar observations were then made in Kenya 109 and in Brazil 68. These findings confirmed views on the prognosis in schistosomiasi s mansoni. not only is polyparasitism present. The manifestations of hepatic schistosomiasis (which Girges considered as being synonymous with Egyptian splenomegaly) were initially the same as those in intestinal schistosomiasis. it is now probable that this conditio n frequently had nothing whatever to do with schistosomiasis. indigestion. The third stage was indicated by the appearance of ascites. mansoni were well-described in the nineteenth century. but infection s with gastrointestinal bacterial and viral pathogens are common. Intestinal schistosomiasis was in turn divided into four phases following "Baoonah itch" (indicating cercarial invasion) and a laten t period: (1) febrile or toxaemic stage lasting three to six weeks . but that hepatomegaly and splenomegaly wer e more common in the moderately and heavily infected children. diarrhoea and tendern ess in the right hypochondrium. hard. Although severe and sometimes fatal infections with S. Similar syndromes to these were described a few years later by Pons i n Puerto Rico96. Before elucidation of the life cycle. A controlled study by Cook and his colleagues of schistosomiasis in the West Indian island of St. (2) dysenteric stage lasting two to three years . as defined by the numbers of eggs excreted in the faeces 20. The second stage was marked by the appearance of an enlarged. (2 ) chronic abdominal pain and periodic mild diarrhoea with occasional blood and mucus in the stools. o ften tender liver and spleen.this was seen in one third of his patients and was typified by thickening of the lower bowel which was ofte n palpable through the abdominal wall. a number of community studies have shed some light on this problem by relating th e clinical manifestations to the int ensity of infection. and the appearance of papillae in th e rectum. In recent years. occasiona l urticaria. They were reiterated again by Gelfand in Southern Rhodesi a (Zimbabwe) who recognized three clinical varieties: (1) an acute phase o f fever and urticaria.250 A History of Human Helminthology delta40. Katz and his col leagues in Brazil followed up 112 patients fo r ten years. who observed 105 patients infected with S. When it was realized that infection was acquired from infecte d snails and that adult worms did not multiply in the human host. although they have tended to con centrate on the more heavily infected individuals. two patients died from haematemesis. however. also in Brazil. their belief that urinary schistosomiasis was of greater importance. in an extensiv e review of schistosomiasis which encompassed clinical and therapeutic aspects of both urinary and intestinal forms of the disease. seven had evolved towards hepatosplenomegaly. DEVELOPMENT OF DIAGNOSTIC METHODS Although Bilharz and Griesinger discover ed that urinary schistosomiasis could be diagnosed in life by finding eggs in the uri ne. In the last several decades. Rather similar results were reported by Kloetzel. some longitudinal studies of the effects o f schistosomiasis have been carried out. It is true that Bilharz did write to von Siebold in Augus t 1852. This presumably devolved from thei r failure to differentiate between laterally and terminally-spined eggs. Thirty years after Bilharz disc overed the worms. Mackie reported that rectal nodules common in Egyptians with schistosomiasis could be twisted off with haemorrhoidal forceps. This concept was accepted by various commentators in thei r textbooks. and neither Bilharz no r Griesinger developed the idea that this phenomenon could be utilized i n diagnosis. Thus. He even added that no ova could be seen in the urine despite careful and repeated micoscopical examination. Thus. is not a major cause of death. "I have also found eggs in the stool of a patient with acute dysentery" 12. but made no mention of any similar examination of the faeces 78. and were aware that ova could be found in the intestinal mucosa at post-mortem examination. but most of the others showed little progres s in the severity of the disease 58. and the relative ease of examining urine compared with faeces. they do no t appear to have paid much attention to diagnosing schistosomiasis by finding eggs in the stools. As late as 1903. but omitted any reference to a simila r . This was almost a throw-away line. it seeme d probable that continuing exposure was necessary for the development o f severe disease. they all recommended examining the urine in order to make th e diagnosis. and that this could influence th e prognosis.Schistosomiasis mansoni 251 speculation that autoinfection might occur. schistosomiasis mansoni. Milton. This concept was supported by the observation that expatriate troops infected during World War I did not develop progressive disease when they were removed from the endemic areas 27. although it may be a cause of considerabl e morbidity. mansoni for five years and found that only seven had died 63. then the characteristic ova could be demonstrate d microscopically. discussed diagnosis b y examination of the urine for eggs. Subsequently. pinpoint or linear in shape and up to several millimetres in width10. The introduction of the proctoscope and sigmoidoscope provided a tool for visualizing the intestinal lesions induced by S. originally described by Kato and Miura in 1954 57. the most important of which is th e Kato technique. In most instances of hepatic schistosomiasis. Bercowitz and his colleagues examined proctoscopi cally 155 Puerto Rican army recruits who had eggs in the faeces. and using nuclear medicine techniques 1. yellowis h nodules of ova could be visualized. simplified by several workers 14. then modified by Komiya and Kobayashi 64. mansoni as a separate species. it was found that liver function tests were only mildly or moderately impaired 89. and varices were frequent in patients with hepatosplenic schistosomiasis 21. thus in one study. manometrically. then a standard. examination of the faece s became a frequent.122. indeed. hyperaemia and friabil ity were common. Similarly. There have been many efforts to develop immu nological assays for the diagnosis of schistosomiasis mansoni. mansoni. although it is clear that Manson in 1902 serendipitously found laterally-spined eggs while looking for hookworm ova in the stools 81.115. as already described. inves tigation in both clinical situations and in epidemiological studies.100. Da Cunha and his colleagues sigmoid oscoped over 2. Fairley described the employment of a complement fixation assay for antischistosomal antibodies in 1919 28. Even though polyps containing eggs were rare in regions outside of Egypt. and found that two thirds of them had small.88.000 patients with schistosomiasis in Brazil and found tha t congestion was the commonest lesion.89. Greany in the Sudan sigmoidoscoped 38 patients with schistosomiasis and found that the most frequent lesions were yellow-whit e pinhead dots. and polyps were rarely met 42.106. Structural damage to the large intestine can be displayed by radiographi c barium enema examination24. Similarly.30. Much attention then turned to developin g laboratory techniques for maximizing the chances of detecting ova in th e stools6.101. however. adapted for quantitative diagnosis by Martin and Beaver84. Thus. eggs may be found in the liver in schistosomiasis.59. however. ova were seen in liver biopsies in 21 out of 45 cases 25.252 A History of Human Helminthology examination of the stools 87. then developed into a "Quick Kato Smear" suitable for rapid quantification of schistosome eggs under field conditions 91. while Taliaferro and his colleagues described a precipitation reaction 113 and an .5. initiated the debate that led to the delineation of S. it was this discovery which. ulcers were seen in one third. It is uncertain who first began routine microscopical examination of th e faeces in order to diagnose schistosomiasis mansoni. it was found that eggs could often be found in biopsies of rectal mucosa 45. rectal polyps were rare. With the realization that it was important to determine the intensity of infection. Following this report. sharpl y demarcated ulcers. these techniques largely fell out favour an d were replaced by quantitative methods. effects on the liver and portal venous system can be investigated radiologically. mansoni than against S. but had no effects on S. This drug was shown by Foster and coll eagues in 1973 to be active against S.108. In the same year. although it appeared to be more useful against the South American than the African strains of th e parasite112. but immunoassays have remained much less useful tha n parasitological diagnostic techniques. Katz and co-workers tested oral and intra muscular administration of the drug i n 24 adults in Brazil with schistosomiasis mansoni and found that the latter route was preferable 60. In 1903. japonicum 37. It was thought initially that patients with schistosomal portal hypertensio n were not likely to develop po rtosystemic encephalopathy as liver function was held to be relatively undisturbed. They removed 148 to 800 worms from three patients. There were reports. He advised removal of polyps. mansoni in rodents and in monkeys. however. Subsequent studies confirmed the efficacy of the drug against S. some differences. haematobium or S. haematobium and metrifonate was found to be of no value at all.62 but sometimes had devastating consequences and did not find lasting recognition. He recommended enemas of starch and opium or copper sulphate in the early stages. . He found that excision of the rectum was rarely necessary 87. and this was said to be sometimes attended by considerable improvement22. oxamniquine is a useful addition to the therapeutic armamentarium in schistosomiasis mansoni. There are.89. Ligation of the hepatic artery had its advocates 49. Noya Benitez performed 22 splenectomies in patients with schisto somiasis and reported in 1947 that it may relieve portal hypertension i f undertaken before liver damag e was excessive 90. niridazole was shown to be less effective against S.54. An ingenious procedure for removal of adult worms from the portal venous system by extracorporeal filtration of blood was described by Goldsmith and colleagues in 1965 41. mansoni. that hepati c dysfunction did supervene 121 and the operation gradually lost favour with many surgeons. but the technique did not live up to expectations and was abandoned. On the other hand. THE SEARCH FOR EFFECTIVE TREATMENT The anthelmintic therapy of schistosomiasis mansoni is broadly similar to that of schistosomiasis haematobia and has been detailed in chapter 8.Schistosomiasis mansoni 253 intradermal test114. Milton reviewed the surgic al management of schistosomiasis of the rectum. but this was frequently no t possible because they were either too numerous or were too high in th e rectum. however. Splenectomy was undertaken for "Egyptian splenomegaly" in the earl y 1920's. Various shunt procedures such as portocaval anastomosis and lieno-renal anastomosis were assessed from time to time 38. As already indicated. mansoni. Although humans have proven to be the major reservoir of infection. haematobium were distinguished have been recounted in chapter 8 . S. Its occurrence in a white man suggested to Manson that the infection must be not uncommon among the indigenous inhabitants. He then dre w attention to the parallels betwee n schistosomiasis and another African disease. mansoni and S. Kitts were infected naturally 15. mansoni infection in nonhumans wa s first reported by Cameron in 1928 after he found that monkeys on the Wes t Indian island of St. Like schistosomiasis haematobia. This was followed by the identification o f the various species of snail intermediate hosts of the parasite in different parts of the world. and with remarkabl e precision and foresight wrote: "It is evident that the distribution of this an d similar parasitic diseases depends on the presence or absence of the efficient . INTRODUCTION OF SCHISTOSOMA MANSONI INTO THE WESTERN HEMISPHERE In 1902. and noted that the latter condition had no w disappeared. Central to the understanding of the epidemiology of schistosomiasis mansoni was the demonstration by Leiper that this infection was transmitted by certain species of snails. and the behavioural habits of the human population which determine both the contamination of water sources with infected faeces and the exposure t o cercaria-laden water. the occurrence of natural infections in rodents in Egypt 66 and in South America 86 was shown. Guinea worm infection. the main determinants of the prev alence and intensity of infection are the presence and density of vector snails. Cyprus and Mauritius. haematobium infection also occurred in the Western Hemisphere. with the realization that this infection but no t S. Subsequently. This was followed by the delineation of the geographica l distribution of S. schistosomiasi s mansoni has been spreading wit h the advent of new irrigation systems and has increased in frequency along the Nile downstream from the Aswan High Dam (see chapter 8). As with schistosomiasis haematobia. Manson implied that both of these infections had been introduced from Africa.254 A History of Human Helminthology UNDERSTANDING THE EPIDEMIOLOGY Early ideas concerning the epidemio logy of schistosomiasis before S. which had been at one time prevalent in parts o f Central and South America. schistosomiasis had hitherto been supposed to be peculiar to Africa. Although he did not specifical ly say so. Over the next few decades. much effort was expended on defining the frequency of the infection and severity of disease in a large number of endemic areas. He then reported the instance of an Englishman who had been infected with schistosomes producing laterally spined eggs while residing in the Wes t Indies. Manson wrote that with the exception of Mesopotamia. mansoni was introduced from Africa. Further support for the slave trade theory was provided by the demonstration tha t infection was common in those places where slaves from endemic areas o f Africa had been imported. Pirajá da Silva wrote that the worm was probabl y introduced into the New World from Af rica by West African slaves. It wa s suggested that these species may have been introduced in water barrel s brought from Africa during the slave trade times. a few workers believe that this worm was autochthonous in Brazil. and had been left behin d when the barrels were washed out and refilled with fresh water 9. although they were usually different species from those seen in Africa. but snails susceptible t o S. Biomphalaria alexandrina pfeifferi and Bulinus tropicus were found in the municipal gardens and in ditches about the city of São Paulo. For example . for example. In 1908. eve n though the latter disease was frequent in parts of Africa and may have been at some time in the past in the Western Hemisphere. haematobium were absent. Brazil. since the Dutch brought in an in ordinately high number of slaves during this period 2. This became explicabl e when Leiper proved that S. Brazil from where da Silva was writing. . While it is the view of the vast majority of investigators that S. reached this opinion on the basis of reports of a disease with symptoms similar to that seen in schisto somiasis mansoni which was said to have existed along the rivers before the arrival of the Portuguese 80. This form of schistosomiasis wa s indeed found to be common in parts of the Americas. particularly during the Dutch administratio n (1630-1654). mansoni were found in various regions of the Americas. and that the schistosome eggs found climatic conditions in America favourable for development 92. mansoni and are most important in transmission. it has been suggested that Recife in Brazil may have been the most important entry point. Although laterally spined eggs were common in South America in the early parts of this century. Magalhães and Dia s. Snails susceptible t o S. haematobium were different species and required different molluscan vectors. Infection was particularly common in the environs of Bahia. beginning in 1550. He postulated that these people were the carriers of schistosomes from Africa. That city was at one time one of the mai n entry ports during the times of the slave trade. haematuria and terminally spined eggs were not. mansoni and S. More recently. there may also have been a small-scale introduction of African vectors. This infection may now be becoming zoonotic.Schistosomiasis mansoni 255 intermediaries" 81. such as northe astern Brazil. for Martins in Brazil in 1958 found that natura l infections were common in wild and domestic rodents 86. While indigenous American snails wer e susceptible to S. 256 A History of Human Helminthology THE EVOLUTION OF PREVENTIVE AND CONTROL MEASURES Measures for the prevention and control of intestinal schistosomiasis ar e similar in many respects to those used in S. haematobium infections. The development of such techniques has already been outlined in chapter 8. The greatest success has attended a multidisciplinary approach. For example , Biaggi reported forty years ago that the prevalence of S. mansoni infection in a rural area of Puerto Rico had been reduced from 44.6% to 4.5% by a combination of treatment, installation of efficient latrines, improvements i n water supply and attempts at biological control of snails, but he commente d that these measures were too expensive to be applied to the whole island 11. Similarly, schistosomiasis was once common in St. Kitts, West Indies, with the prevalence of infection as late as 1932 being estimated to be as high as 25%. The infection has now disappeared, presumably as a result of unplanne d environmental improvements 35. Various methods for the control of schistosomiasis mansoni have bee n assessed in various parts of the world, but perhaps the most elegant of these studies were carried out on the West Indian island of St. Lucia by Jordan and his colleagues. The efficacies of different control techniques including snai l control, chemotherapy and provision of safe water supplies were investigated. Although all methods produced similar results, it was concluded that chemotherapy (hycanthone plus or minus oxamniquine) was the cheapest and most rapidly effective method of achieving transmission control and also provided disease control. Snail control (with Bayluscide), however, did not requir e either population cooperation or a stable community. Installation of safe water supplies was the costliest technique and required education and cooperation of the population, but provided other social and medical benefits 53. These techniques are being used in varying combinations, as far as practicable and economically feasible, in various parts of the world. REFERENCES 1. ALMEIDA FC, LUZ FF. Direct operative portography in hepatosplenic schistosomiasis mansoni. Gazeta Médica da Bahia 70: 1-15, 1970 2. ALMEIDA MACHADO P. 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GOLDSMITH EI, LUZ FF, PRATA A, KEAN BH. Surgical recovery of schistosomes from the portal blood. Treatment of parasitization in man. Journal of the America n Medical Association 199: 235-240, 1967 42. GREANY WH. Schistosomiasis in the Gezira irrigated area of the Anglo-Egyptia n Sudan. II. Clinical study of schistosomiasis mansoni. Annals of Tropical Medicine and Parasitology 46: 298-310, 1952 43. GRIESINGER W. Klinische und anat omische Beobachtungen. Über die Krankheiten von Egypten. Archiv für Physiologie Heilkunde 13: 528-575, 1854. Partly translated in 61 44. HARLEY J. On the endemic haema turia of the Cape of Good Hope. Medico-Chirurgical Transactions 47: 55-72, 1864. Abstracted in Lancet i: 156-157, 1864 45. HERNÁNDEZ MORALES F, MALDONADO JF, PRATT CK. The diagnosis o f schistosomiasis by a rectal biopsy technique. American Journal of Tropical Medicine 26: 811-820, 1946 46. HOEPPLI R. Parasitic disease in Africa and the Western Hemisphere. D. Helmint h infections. Acta Tropica, Supplement 10: 111-150, 1969 47. HOLCOMB RC. The West Indian bilharziosis in its relation to the Schistosomum mansoni (Sambon 1907), with memoranda on ten cases. United States Naval Medica l Bulletin 1: 55-80, 1907 Schistosomiasis mansoni 259 48. HUTCHINSON HS. The pathology of bilharziasis. American Journal of Pathology 4 : 1-16, 1928 49. IBRAHIM H. Combined ligation of hepatic and splenic arteries in Egyptia n splenomegaly. Journal of the Egyptian Medical Association 40: 253-269, 1957 50. INTERNATIONAL COMMISSION ON ZOOLOGICAL NOMENCLATURE. Opinion 735. Biomphalaria Preston, 1910 (Gastropoda): Grant under the plenary powers o f precedence over Planorbina Haldeman, 1842, Taphius H. and A. Adams, 1855, an d Armigerus Clessin, 1884. Bulletin of Zoological Nomenclature 22: 94-99, 1965 51. ITURBE J. Intermediate host of Schistosoma mansoni in Venezuela. Journal of Tropical Medicine and Hygiene 20: 130-131, 1917 52. ITURBE J, GONZALEZ E. Quelques observations sur les cercaires de la vallée d e Caracas (Première partie). Laboratorio Iturbe, pp 18, 1919. Abstracted in Tropica l Diseases Bulletin 14: 142-143, 1919 53. JORDAN P. Schistosomiasis - research to control. American Journal of Tropica l Medicine and Hygiene 26: 877-886, 1977 54. JUSTINIANO RT. Portocaval shunt in the treatment of bleeding esophageal varices due to schistosomiasis. (preliminary report). Boletín de la Asociación Médica de Puerto Rico 55: 266-270, 1963 55. KARTULIS S. Ueber das vorkommen der Eier des Distomum haematobium Bilharz, in den Unterleibsorganen. Archiv für pathologische Anatomie und Physiologie und fü r klinische Medicin (Virchow) 99: 139-145, 1885 56. KARTULIS S. Bilharzia. Lancet ii: 364, 1885 57. KATO I, MIURA M. Comparative examin ations. Japanese Journal of Parasitology 3: 35, 1954 58. KATZ N, BRENER Z. 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Mortality in chronic splenomegaly due to schistosomiasis mansoni : follow-up study in a Brazilian population. Transactions of the Royal Society of Tropical Medicine and Hygiene 61: 803-805, 1967 64. KOMIYA Y, KOBAYASHI A. Evaluation of Kato's thick smear technic with a cellophane cover for helminth eggs in feces. Japanese Journal of Medical Science an d Biology 19: 59-64, 1966 65. KOPPISAN E. Studies on schistosomiasis in Puerto Rico. VI. Morbid anatomy of th e disease as found in Puerto Ricans. Puerto Rico Journal of Public Health and Tropica l Medicine 16: 395-455, 1941 66. KUNTZ RE. Natural infection of an Egyptian gerbil with Schistosoma mansoni . Proceedings of the Helminthological Society of Washington 19: 123-124, 1952 67. LAWTON FB. The early symptoms following infection by Schistosoma mansoni . Medical Journal of Australia ii: 247-250, 1917 68. LEHMAN JS, MOTT KE, MORROW RH, MUNIZ TM, BOYER MH. The intensity and effects of infection with Schistosoma mansoni in a rural community in northeas t Brazil. American Journal of Tropical Medicine and Hygiene 25: 285-294, 1976 69. LEIPER RT. Half yearly report to the Colonial Office, May 1908. Cited in 72 260 A History of Human Helminthology 70. LEIPER RT. Letter to P. da Silva (February 1909). Cited in 18 71. LEIPER RT. On the relation between the terminal-spined and lateral-spined eggs o f Bilharzia. British Medical Journal i: 411, 1916 72. LEIPER RT. Report on the results of the Bilharzia mission in Egypt, 1915. Journal of the Royal Army Medical Corps 30: 235-260, 1918 73. LOOSS A. What is "Schistosomum mansoni" Sambon 1907? Annals of Tropica l Medicine and Parasitology 2: 153-191, 1908 74. LOOSS A. Some notes on the Egyptian Schistosoma haematobium and allied forms. Journal of Tropical Medicine and Hygiene 14: 177-182, 1911 75. LUTZ A. Observações sobre a evolução do Schistosomum mansoni . Nota previa. Brazil Medico 30: 385-387, 1916 76. LUTZ A. Observações sobre a evolução do Schistosomum mansoni . Brazil Medico 31: 81, 89, 1917 77. LUTZ A. O Schistosomum mansoni e schistosomose segundo observações feitas n o Brazil. Memorias do Instituto Oswaldo Cruz 11: 121-155, 1919 78. MACKIE J. Bilharzia haematobia in connexion with a form of dysentery in Egypt . British Medical Journal ii: 661, 1882 79. MADDERN FC. The incidence of bilharziosis in Egypt and its clinical manifestations. British Medical Journal ii: 965-969, 1910 80. MAGALHÃES BF, DIAS CB. Esquistossomose de Manson. Estudo Memorias d o Instituto Oswaldo Cruz 41: 363-446, 1944 81. MANSON P. Report of a case of Bilharzia from the West Indies. British Medical Journal ii: 18941895, 1902 82. MANSON P. Tropical diseases. A manual of the disease of warm climates. third edition, Cassell and Co., pp 756, 1903 83. MANSON-BAHR P, FAIRLEY NH. Observations on bilharziasis amongst the Egyptian Expeditionary Force. Parasitology 12: 33-71, 1920 84. MARTIN LK, BEAVER PC. Evaluation of Kato thick-smear technique for quantitative diagnosis of helminth infections. Ameri can Journal of Tropical Medicine and Hygiene 17: 382-391, 1968 85. MARTINS A V. Contribuçã o ao estudo do gênero Australorbis Pilsbry 1934. Memórias do Instituto Ezequiel Dias 2: 5-61, 1938 86. MARTINS AV. Non-human vertebrate hosts of Schistosoma haematobium and Schistosoma mansoni . Bulletin of the World Health Organization 18: 931-944, 1958 87. MILTON F. Bilharziosis surgically considered. Lancet i: 866-869, 1903 88. MOUSA AH, EL-GAREM A, SAIF M, EL-ABDIN AZ. The significance of estimating the hepatic blood flow in hepatosplenic bilharzial cases by the radiogold clearance and uptake methods and its value in determining the extent of porta-systemic collaterals . Journal of Tropical Medicine and Hygiene 70: 55-59, 1967 89. NEL CJ, HONIBALL PJ, VAN WYK FA. Portal hypertension in schistosomiasis. South African Journal of Surgery 12: 233-239, 1974 90. NOYA BENITEZ J. Splenectomy in schistosomiasis. Preliminary report. Puerto Ric o Journal of Public Health and Tropical Medicine 23: 247-255, 1947 91. PETERS PA, EL ALAMY M, WARR EN KS, MAHMOUD AA. Quick Kato smear for field quantification of Schistosoma mansoni eggs. American Journal of Tropical Medicine and Hygiene 29: 217-219, 1980 92. PIRAJÁ da SILVA M A. Contribução para o estudo da schistosomiasis na Bahia. Brazil Medico 22: 281-283, 441-444, 451-454, 1908. Partly translated in 61 93. PIRAJÁ da SILVA M A (cited as da SILVA P). Contribution to the study o f schistosomiasis in Bahia, Bra zil. Journal of Tropical Medicine and Hygiene 12: 159-163, 1909 94. PIRAJÁ da SILVA M A. La schistosomose à Bahia. Archives de Parasitologie 13 : 283-302, 1909 95. PIRAJÁ da SILVA M A. Cited in 18 Schistosomiasis mansoni 261 96. PONS JA. Studies on schistosomiasis mansoni in Puerto Rico. V. Clinical aspects o f schistosomiasis in Puerto Rico. Puerto Rico Journal of Public Health and Tropica l Medicine 13: 171-254, 1937 97. PORTER A. The invertebrate (molluscan) hosts of Schistosoma mansoni and Fasciola hepatica in South Africa. Medical Journal of South Africa 16: 75-76, 1920 98. PRESTON. Annals and Magazine of Natural History 6: 535, 1910 99. REPORT OF A STUDY GROU P. Bilharzia snail vector identification and classification (Equatorial and South Africa). World Health Organization Technical Report Series, No. 90, pp 1-22, 1954 100. RITCHIE LS. An ether sediment ation technique for routine stool examinations. Bulletin of the United States Army Medical Department 8: 326, 1948 101. RODRIGUEZ HF. Schistosomal hepa tosplenomegaly. Boletín de la Asociación Médica de Puerto Rico 48: 393-403, 1956 102. SAMBON LW. Descriptions of some new species of animal parasites. Proceedings of the Zoological Society of London. No. 19, pp 282-283, 1907 103. SAMBON LW. New or little known African entozoa. Journal of Tropical Medicine and Hygiene 10: 117, 1907 104. SAMBON LW. Remarks on Schistosomum mansoni . Journal of Tropical Medicine and Hygiene 10: 303-304, 1907 105. SAMBON LW. What is "Schistosomum mansoni" Sambon 1907? Journal of Tropical Medicine and Hygiene 12: 1-11, 1909 106. SCOTT JA. Dilution egg counting in comparison with other methods for determining the incidence of Schistosoma mansoni. American Journal of Hygiene 25: 546-565, 1937 107. SHAW AF, GHAREEB AA. The pathogenesis of pulmonary schistosomiasis in Egypt with special reference to Ayerza's disease. Journal of Pathology and Bacteriology 46: 401-424, 1938 108. SHIROMA M, OKUMURA M, MEIRA JA, FERREIRA JM. Cirurgia da hipertensão portal na esquitossomose mansônica hepatosplênica. Avaliação clínica de 150 casos de anastomose espleno-renal. Revista do Hospital das Clínicas; Faculdade de Medicina , Universidade de São Paulo 22: 309-337, 1967 109. SIONGOK TK, MAHMOUD AA, OUMA JH, WARREN KS, MULLER AS , HANOKA AK, HOUSER HB. Morbidity in schistosomiasis mansoni in relation t o intensity of infection: study of a community in Machakos, Kenya. American Journal of Tropical Medicine and Hygiene 25: 273-284, 1976 110. SYMMERS WStC. Note on a new form of liver cirrhosis due to the presence of ova of Bilharzia haematobia . Journal of Pathology and Bacteriology 9: 237-239, 1904 111. SYMMERS WStC. A note on a case of bilharzial worms in the pulmonary blood in a case of bilharzial colitis. Lancet i: 22, 1905 112. SYMPOSIUM DE OXAMNIQUINE. Rio de Janeiro, Brasil, Junho, 1973. Revista do Instituto de Medicina Tropical de São Paulo 15: Supplement, pp 1-175, 1973 113. TALIAFERRO WH, HOFFMAN WA, COOK DH. A precipitin test in intestina l schistosomiasis. Journal of Preventive Medicine 2: 395-414, 1928 114. TALIAFERRO WH, TALIAFERRO LG. Skin reactions in persons infected wit h Schistosoma mansoni. Porto Rico Journal of Public Health and Tropical Medicine 7 : 23-35, 1931 115. TOMB JW, HELMY MM. The diagnosis of in testinal schistosomiasis by sedimentation. Transactions of the Royal Society o f Tropical Medicine and Hygiene 25: 181-185, 1931 116. WALLERSTEIN RS. Longevity of Schistosoma mansoni: observations based on a case. American Journal of Tropical Medicine 29: 717-721, 1949 117. WARREN KS. The immunopathogenesis of schistosomiasis: a multidisciplinar y approach. Transactions of the Royal Society of Tropical Medicine and Hygiene 66 : 417-434, 1972 118. WARREN KS. Regulation of the prevalence and intensity of schistosomiasis in man: immunology of ecology? Journal of Infectious Diseases 127: 595-609, 1973 262 A History of Human Helminthology 119. WARREN KS. The pathology, pathobiology and pathogenesis of schistosomiasis . Nature, London 273: 609-612, 1978 120. WARREN KS, MAHMOUD AA, CUMMINGS P, MURPHY DJ, HOUSER H B . Schistosomiasis mansoni in Yemeni in California: duration of infection, presence o f disease, therapeutic management. American Journal of Tropical Medicine and Hygiene 23: 902-909, 1974 121. WARREN KS, REBOUÇAS G, BAPTISTA AG. Ammonia metabolism and hepati c coma in hepatosplenic schistosomiasis: patie nts studied before and after portacaval shunt. Annals of Internal Medicine 62: 1113-1133, 1965 122. WELLER TH, DAMMIN GJ. The acid-ether centri fugation and the zinc sulfate flotation techniques as methods for the recovery of eggs of Schistosoma mansoni . American Journal of Tropical Medicine 25: 367-374, 1945 123. WRIGHT CA. Tropical Diseases Bulletin 63: 862, 1966 124. ZANCAROL G. A specimen of Bilharzia, &c., with ova in the tissues of the bladder and large intestine. Transactions of the Pathological Society of London 33: 410-412, 1882. Abstracted in British Medical Journal i: 13, 1882 and Lancet i: 16, 1882 Table 9.1. Landmarks in schistosomiasis mansoni __________________________________________________________________ 1851 1882 Bilharz saw but did not recognize adult worms Zancarol and Mackie remarked that in Egyptian schistosomiasis, eggs found in the bladder had terminal spines while those in the bowel had lateral spines 1882 Mackie emphasized the dysenteric symptoms of many patients with Egyptian schistosomiasis 1885 Kartulis described schistosome eggs in the liver 1902 Manson reported a patient with schistosomiasis acquired in the Western Hemisphere; the eggs were in the stools, not in the urine, and had lateral spines 1904 Symmers described clay-pipe stem fibrosis of the liver 1907 Sambon gave the name Schistosoma mansoni to the worm producing laterally spined eggs 1916 Leiper discovered the molluscan vectors of Egyptian schistosomiasis and proved the specific identities of S. mansoni and S. haematobium 1918 Christopherson reported the efficacy of tartar emetic 1940+ Kikuth and Gönnert showed that miracil D had schistosomicidal activity in experimentally infected animals 1947 Blair, Hawking and Ross introduced therapy with miracil D 1964 Lambert and Ferreira reported that niridazole was active 1967 Pellegrino, Katz and Scherrer showed that hycanthone was effective 1973 Oxamniquine was reported by various workers to be effective in treatment 1977 Praziquantel was reported by various investigators to be effective in experimental animals 1979 Katz, Rocha and Chaves reported that praziquantel was effective in humans __________________________________________________________________ Chapter 10 Schistosoma japonicum and SCHISTOSOMIASI S JAPONICA SYNOPSIS Common name: Oriental blood fluke, causes Oriental schistosomiasis Major synonyms: Bilharzia japonica, Schistosoma cattoi Distribution: China, Philippines, Indonesia, (Japan) Life cycle: similar to S. mansoni except that the vectors belong to the genus Oncomelania Definitive hosts: humans, dogs, cats, rodents, water buffalo, pigs, horses, sheep Major clinical features: similar to schistosomiasis mansoni; also epilepsy Diagnosis: demonstration of eggs in faeces, rectal mucosa, or liver biopsy Treatment: niridazole, praziquantel, (tartar emetic) DISCOVERY OF THE EGG Ova of the parasite now known as Schistosoma japonicum were first discovered in 1888 by Tokuho Majima (pen-name, Naganori) in Japan when he made a postmortem examination of a man who had been suffering with ascites and peripheral oedema. Majima noted that the spleen of this patient wa s enlarged to five times the normal weight but that the liver was shrunken an d contracted. The liver, moreover, had granular nodules both on its surface and in the parenchyma amongst thickened connective tissue. When histologica l sections of the liver were prepared: It was found most surprisingly and unexpectedly that with the thickened interlobular tissue there were countless parasite eggs, and these were located only in the connective tissue....these eggs were oval....in shape and varied in size from 0.065 to 0.06 mm in length and 0.05 to 0.04 mm in diameter. The shells of the eggs did not possess small covers (opercula). There were two kinds of eggs; the first type was pale yellow in color with contents of a granular nature streaked with brownish-black pigment....The second type had only the egg shell with no contents and were, therefore, colorless and transparent.72 Majima wondered where the eggs came from, and with excellent logic bu t miserable luck, opened the bile duct and the portal vein in the hope of finding adult worms. He was unsuccessful - if he had been, he would have anticipated the discovery of S. japonicum by 16 years. Majima was not able to examine the faeces of this patient but predicted that eggs might have been found there . 263 264 A History of Human Helminthology Finally, he explained why he had reported this case: I have set down my experience in the hope that in a parasite-ridden country like Japan, a summary of the microscopic observations and clinical record might be useful to students in the future.72 Similar eggs were found subsequently by Yamagiwa (1890) 119, Kurimoto (1893)55, Kanamori (1898) and Fujinami (1904) in various organs, especially the liver, of patients who had died in parts of Japan where an illnes s characterized by hepatosplenomeg aly, diarrhoea, anaemia, wasting, ascites and peripheral oedema was common. Some of these authors believed that the ova played a role in the genesis of this disease, as did Kawanishi (pen-name Kasai), who in 1902 was the first to find eggs in the faeces of patients 52. In April 1904, Fujiro Katsurada, professor of medicine at Okayama Medical College in Japan went to Yamanashi Prefecture Hospital and examined twelve patients with this syndrome. In five of these persons, he found ova of th e parasite now known as S. japonicum in the faeces. Although he is quoted a s saying in one paper "Until now, the eggs have been unknown to the medica l world"49 this appears to be a mistranslation for two reasons. Firstly, later in the same paper, he refers to earlier discoveries of the same kind of eggs b y Yamagiwa and Kanamori. Secondly, in a subsequent paper and translated by a different person, the following passage appears: Yamagiwa, Kurimoto, Fujinami and others observed cases in which in several organs....in cadavers from infected areas, numerous eggs of a hitherto unknown parasite were found.50 In any event, Katsurada described the eggs in detail, noting that they were oval in shape, gave their dimensions, commented upon a transparent membran e inside the shell, mentioned that the egg shells were devoid of any spine similar to that seen in S. haematobium eggs, and described the miracidium which was often seen within an egg. In one paper, he stated that the egg had a n operculum 49, but later corrected this error 50. In an attempt to find ova with morphological characteristics similar to those of these eggs, Katsurada reviewed e very known parasite and concluded that the most similar eggs were produced by the trematode, S. haematobium, but realized that the eggs he had found were shorter and had no spine. When h e studied the miracidia from his specimens and compared them with th e descriptions given for the miracidia of S. haematobium, he could discern little difference between the two parasites, except that he could find no evidence of the two large gland cells in the anterior part of the body of the miracidium that were said by Looss to be typical of S. haematobium. Consequently, Katsurada wrote "therefore, I cannot but help conclude that the egg which I discovere d and that of Bilharzia haematobium are similar, but not exactly the same" 49. For a number of years it was thought that, in contradistinction to th e terminally spined ova of S. haematobium and the lateral-spined eggs of S. mansoni, S. japonicum ova did not have a spine. In 1910, however, Leipe r examined 50 eggs from four human cases and three infections in dogs an d Schistosomiasis japonica 265 discovered by rolling them around on a micr oscope slide that a small, knob-like projection was always present 60. Evidence of the antiquity of schistosomiasis ja ponica in eastern Asia has been provided recently by finding typical eggs in human tissue. In 1971, a corps e which had been buried 2,100 years pr eviously in Hunan Province of China was exhumed and characteristic S. japonicum eggs were recovered from digested liver. Four years later, eggs were found similarly in a corpse which had been buried 100 years earlier than the previous one 75. DISCOVERY OF THE ADULT WORMS Following his initial observations, Katsurada hypothesized that, since thes e eggs were not found in the faeces of every patient with the endemic syndrome, and as greater numbers of eggs were recovered from purged stools, it wa s unlikely that the adult worms dwelt within the gastrointestinal tract or an y lumen connected directly with it. It was more probable that the worms resided in the walls of the gut or in the visc era connected closely with it. It was obvious to him that the only way to find these parasites and clarify the pathology of the infection was to perform an autopsy on a patient with the endemic disease . Unfortunately, Katsurada had no opportunity to undertake such a post-mortem examination, but he was able to review specimens of three livers and on e intestine obtained at autopsy a few years earlier by Drs. Shimohira ( = Shimodaira) and Muramatsu. In this material, he found similar eggs. Thi s evidence, together with the observations of earlier investigators, particularl y Kanamori who had found similar ova in a rectal tumour and in a cirrhotic liver, left Katsurada in little doubt that not only was this parasite the cause of th e syndrome, but that it was most likely that the adult worms lived in the porta l venous system. As Katsurada knew that some ot her trematodes endemic in humans in Japan, such as Clonorchis sinensis and Paragonimus westermani, could also be found in cats and dogs, he killed a cat an d two dogs obtained from one of the endemic areas. He noted nothing relevant in the dogs, but in the cat, killed on 9 Apri l 1904, Katsurada found two kinds of parasitic eggs in the liver, one of whic h was the same as he had seen in human faeces an d in the specimens of liver from three human autopsies. But in addition to the ova, he found adult worms: white pieces of parasites were found in the large branch of the portal vein in the portal system. After being suitably prepared, these worms were studied microscopically. They were males, probably of the Bilharz's Schistosoma haematobia (or belonging to the same genus) and had not been seen in Japan before. 49 In June 1904 Katsurada published all his f indings to that time. He described the eggs and the male worms, and concluded tha t the eggs and worms were directly related, as a child to its parent 48. This view was disputed by a scholar of the subject, so Katsurada obtained a 266 A History of Human Helminthology second cat from the same village (Okamada in Yamanashi Prefecture) an d found 24 male and eight female adult worms in the portal and mesenteric veins of this animal. He then described both sexes of the worm in detail, including the appearances of the eggs within the female worms, and emphasized th e differences between the parasite that he had found and S. haematobium. These results appeared in his second paper published in August 1904. At this time, he called the parasite Schistosoma haematobium japonicum : "for the time being, I want to call the parasite that I discovered, and which belongs to th e genus Schistosoma, 'Schistosoma haematobium japonicum'" 49. In October 1904, he wrote a third account, which was also published in German i n December 1904 then translated into English in April of the following year, the worm on this occasion being labelled Schistosoma japonicum 50. Katsurada's discovery was confirmed later in the same year by other Japanese workers. In May 1904, Fujinami in Hiroshima (who had earlier found eggs in the viscera of the first fatal case of Katayama disease that he had encountered), discovered a partly damaged female worm in a branch of the portal vein of a second patient who had died. He regarded this worm as a Distoma haematobium and apparently believed initially that it was the first suc h specimen to be found in Japan. In this patient, he also found the characteristic ova in the liver, intestinal wall, mesenteric glands and pancreas 33. Soon thereafter, Tsuchiya in Yamanashi found the parasite in cats, dogs an d humans109. These observations were all either unpublished or inaccessible to him in the Japanese literature when the Englishman, John Catto, discovered worms of the same type in 1904. Catto was res ident medical officer at St. John's Island quarantine station in Singapore when cholera broke out on a passenger ship from China. One of the travellers, a man from Fukien, died from cholera, but wa s noted during life to have hepatosplenomegaly. At autopsy, the rectovesica l pouch was almost obliterated by adhesions, the mesentery was thickened and contained enlarged lymph nodes, the l iver was enlarged and cirrhotic, the colon was thickened with the mucosa being swollen, hyperaemic, friable an d ulcerated, and the spleen was pigmented. Portions of the liver, mesenteri c lymph nodes and bowel were preserved and histol ogical sections were prepared in Singapore by Dr Finlayson and at the Kuala Lumpur Research Institute by Dr Daniels. These disclosed "numerous small, oval bodies having a smooth , stout capsule"17 but opinions differed as to whether they were coccidia or the ova of some unknown parasite. In the event, the case was published in th e Journal of the Malaya Branch of the British Medical Association as one of human coccidiosis. Catto then returned to England and re-examined th e material at the London School of Tropical Medicine. This time, it becam e evident that there were not only ova but also filariform larvae (? Strongyloides - author) in the large intestinal mucosa. The sections were shown at th e Medical Research Club in London but no definite conclusion was reached, so Schistosomiasis japonica 267 samples were sent to an eminent German authority who considered that the y were neither coccidia nor trematode ova, but the eggs of a nematode o f unrecognizable species. At Patrick Manson's suggestion, Catto began to section systematically all the preserved tissues. He found nematode larvae in smear s prepared from the large intestine, a minute adult nematode in an artery of the mesorectum, and a nematode larva in a mesenteric lymph node. Stimulated by these observations, and no doubt misled by the German opinion, Manson and Catto presented the case to a meeting of the British Medical Association i n Oxford in July 1904 as that of an infection with a new nematode: "The parasite would seem to be an oviparous nematode of minute dimensions and o f unknown species" 74. Catto continued his dissections and eventually found male and female adult trematode worms in the mesenteric vessels, although neither he nor exper t pathologists could be certain whether they were arteries or veins. Within th e bodies of the female worms Catto now saw ova corresponding to the ova l bodies in the viscera and realized that he was dealing with concomitan t nematode and trematode infections. Manson then sent specimens to the International Zoological Congress at Berne, Swi tzerland, where they were examined by Blanchard, Looss, Ward, Stiles, Grassi and others, all of whom agreed that the parasite was a schistosome and new to science. Catto then presented a n updated version of his findings, describing both the autopsy features and th e adult worms, to a meeting of the Pathological Society of London on 1 5 November 190416. Blanchard subsequently named the parasite Schistosoma cattoi in Catto's honour, then Catto published a detailed record of the parasite under that name in the British Medical Journal of 7 January 1905 17. Further investigations revealed the identity of this parasite with the on e described by Katsurada so, by the law of priority, Katsurada's designation , Schistosoma japonicum, stands as the correct name for this helminth. Thus, the worm was discovered independently by several workers. Faust and Melene y have placed these events in perspective well: As has frequently been the case in many important contributions to science, several workers attack the same problem contemporaneously, but without knowledge of each other's investigations. Only the circumstance of time gives one the honor which the other quite equally deserves. Such is the case with Schistosoma japonicum Katsurada.29 Katsurada in Yamanashi attacked the problem logically and systematically; he began with patients with a particular clinical syndrome, found eggs in thei r stools, confirmed their presence in the viscera of other patients, surmised that adult worms must live in the portal veno us system, found the male worm in that position in a naturally-infected cat, then pursued the quest relentlessly until he found female worms in another animal. Fujinami in Hiroshima, having earlier found the eggs in another of his patients, was beaten to the punch by a mer e month or so, but was without doubt t he first to find the female adult worm, and the first to find an adult schistosome in a human being. Finally, Catto i n 268 A History of Human Helminthology Singapore and England, and completely unaware of the Japanese discoveries, was tenacious enough, after meandering dow n several false alleys, to eventually find adult worms a matter of several months after the Japanese researchers . Furthermore, although the exact time sequence is unclear, it is probable tha t Catto, or possibly Tsuchiya in Japan, was the first person to find male adul t schistosomes in a human being. DISCOVERY OF THE PERCUTANEOUS ROUTE OF INFECTION When the adult forms of S. japonicum were discovered, it was clear that th e infection must be transmitted in a fashion similar to that of S. haematobium. But, as already discussed in chapter 8, the life cycle of that parasite too wa s quite obscure, with protagonists of the direct infection theory and th e intermediate host school each ardently defend ing their own particular view. The speed with which the Japanese investigators worked out the life cycle of S. japonicum is little short of remarkable, considering that it took only nine years from Katsurada's discovery of the adult worms until Miyairi and Suzuk i demonstrated transmission through snail intermediate hosts. This contrast s starkly with the 64 years between Bilharz's discovery of S. haematobium and Leiper's elucidation of the life cycle of that worm - and that largely followed the precedent set by the Japanese. In defence of the European investigators , however, it must be remarked that two factors worked in favour of the Oriental scientists. Firstly, Miyairi and Suzuki found snails susceptible to infection and naturally infected with S. japonicum at almost their first attempt, whereas a number of European investigators examined many different species with a conspicuous lack of success. Secondly, although animals can be infecte d experimentally with S. haematobium and S. mansoni, occidental schistosomiasis in nature is principally a disease of humans. Oriental schistosomiasis, on the other hand, is a major zoonosis with humans and animals being equally infected; this was known as early as 1847 for Fujii then wrote that even th e cattle and horses were not immune to the affliction 32. This facilitated research enormously for simple animal models were th erefore available for experimental elucidation of the life cycle. Fujinami recognized this when he looked back on the early years of schistosomiasis research in Japan: animal experiments have been easily carried on, as the subjects of the experiment could be infected by immersing them in water of the ditches in the endemic area. The animal experiments have led to the solution of many interesting problems in the pathology of the disease.34 Animal experimentation was indeed the key to success, but the key had first to be found. It was Fujinami himself, in collaboration with Nakamura, a n assistant professor of pathology at Kyoto Unive rsity, who made the fundamental discovery. Because the adult schistosomes lived in the portal venous syste m and were often found in the intestinal wall, many Japanese investigators thought Schistosomiasis japonica 269 it likely that infection was acquired via the gastrointestinal tract, possibly by the ingestion of worms in contaminat ed water. On the other hand, the development of leg rashes and subsequent disease in farme rs working in rice fields suggested that infection might occur through the skin. Fujinami and Nakamura therefore devised an experiment to test the various hypotheses. They decided to use cows since these animals were not onl y susceptible to infection, but they were also large and docile enough to be made to stand in water with only the hooves be ing soaked and without water touching the anus and genitalia, thus avoiding the possibility of infection via the mucous membranes of these organs. They used 17 cows up to one year of age an d which had been obtained in Hiroshima ci ty where the infection was absent. The experiment was begun on 7 June 1909 with the beasts being divided into a number of groups. The first gr oup of six calves was given only boiled food and water, and except on these occasions, th eir mouths remained covered. Each day they were taken out of the barn and stood in water, three of them in the mud of a rice paddy and the other three in a river which received great volumes o f water from the rice fields. All of these animals became infected with S. japonicum, but much larger numbers of adult worms were found in the cows that had been allowed into the rice fields. A second group of seven calves had their legs washed with soap and alcohol, then oiled and covered wit h water-proof, protective leg bags. Four o f these animals ate and drank in the rice fields, while three of them were taken to the river banks to feed. Six of these cows remained uninfected, and a solitary worm pair was recovered from th e seventh animal. A third group of two cows was fed and watered like the first group. One cow was confined to the barn; no infection developed. The other animal was placed in an irrigation canal for nearly five and a half hours on one day only, nevertheless, it became infected with 31 worms. Finally, no special measures were taken for a fourth group of two cows which were permitted to roam freely; both animals became infected. Fujinami and Nakamura therefore concluded that infection was acquired by penetration of the skin 35,36: The great difference between the findings for group A and B is obvious - like snow and charcoal - and we feel that the problem of the mode of entry of the infection, which has vexed scientists for so long, has at last been incontrovertibly solved" 35 Further, they deduced that infection could be acquired easily in a short space of time by contact with contaminated water, but that the risk of infection was greater in the stagnant waters of the paddy fields and small irrigation canal s than in the fast-flowing waters of the rivers. The two researchers found schistosome s in different stages of growth in most animals. One cow, however, had been exp osed on only one occasion, and when it was killed 26 days later, small mal e and female worms were found in copula. Although no eggs were detected, this observation led Fujinami and Nakamura to write that: "the time required for the parasite to grow is comparativel y short"36. This conclusion was verified by experiments which they undertoo k 270 A History of Human Helminthology concurrently with dogs. These animals were kept secluded in cages an d provided with uncontaminated food and water. At various intervals, they were allowed outdoors into the rice fields and river. They were killed 23 or 54 days later. In the dog killed after 23 days, small (4-5 mm) but mature male an d female worms in copula were found, but again, no eggs were seen. In the dog killed 54 days after infection, schistosomes 1 .0-1.3 cm long were recovered and the female worms contained eggs. Similar results were obtained with rabbits, and when the results from the three spec ies were compared, it became apparent that ova were first produced five to six weeks after exposure, with egg s appearing in the faeces shortly thereafter. Thus, Fujinami and Nakamura proved that infection occurred via the skin , but they recognized that how it happened, and the nature of the antecedent and subsequent events still remained unclear: The life cycle before they (adult worms) are found in the portal circulation is not yet known. The connection between the small worm (miracidium) which during the warm season leaves the egg shell which had been deposited in the soil and water and the very young, immature worms in the portal vein must await serious study in the future.36 The demonstration by Fujinami and Nakamura that infection was effected by penetration of the skin was confirmed later that year by Katsurada an d Hasegawa who, in another district of Japan, infected a dog and a cat. It was also demonstrated unexpectedly by Matsuura who had the misfortune to becom e infected accidentally while wading in foul water. As will be discussed later , microscopical confirmation of t he direct penetration of the skin by schistosome larvae, albeit of uncertain specificity, was provided in 1912 by Miyagawa 81. ELUCIDATION OF THE MODE OF TRANSMISSION: DISCOVERY OF THE LARVAL STAGES AND THE SNAIL INTERMEDIAT E HOSTS The answer to the part of Fujinami and Nakamura's question concerning th e events leading up to percutaneous infection was provided four years later b y Keinosuke Miyairi and Masatsagu Suzuki, both of Kyoto University. They published their results first in Japanese in 1913 86 (an English abstract of this paper appeared in the March 1914 issue of the Tropical Diseases Bulletin ), then a German version was published in 1914 87. It had been known for a number of years that when eggs hatched, miracidia were released. In 1904, Kawanishi had reported that when: provided with a little warmth, it (the larva) immediately comes out of its shell....When they first leave the shell, the larvae look like wine bottles. After one day they become larger and assume many different shapes.52 Consequently, Miyairi and Suzuki began wi th the question as to what happened to schistosome ova deposited in animal and human excrements in the open air. Schistosomiasis japonica 271 They found a small ox infected with schistosomes which provided a constant source of material for their exper iments. First, they observed the motions of the miracidium within each egg, then they studied the hatching of the larva. At a village called Kisi-mura of Miyoki-gun in Saga Prefecture, they found S. japonicum eggs in human faeces left on the roadside. They therefore searched carefully in the surrounding area and eventually: succeeded in finding a certain species of snail in a little ditch by a rice field in the village. The snail which apparently had no lungs had a brownish yellow shell which was very smooth on the surface and was turning in a clockwise direction. The shell could be easily crushed and had seven whorls....As amateurs, we couldn't tell the exact name of the snail.86 Miyairi and Suzuki collected these snails and kept them alive in receptacle s containing fresh water and cabbage leaves. They then took young snails which proved to be free of naturally-acquired infect ion and mixed them in a basin with miracidia freshly prepared from S. japonicum ova. They described graphically the subsequent course of events: The way a fresh miracidium rushes up to its host can be compared to that of a hungry tiger coming out his cage to hunt for something to eat" 86. The miracidia attached themselves to the free body surface of the snails then penetrated to the interior: the animal (miracidium) makes its head sucker as thin as possible, pushes it between the snail's epidermal cells, and stretches its cylindrical body as long as possible. With a jerk it pulls itself together so that the base of the inserted proboscis cone and the epidermal slit becomes wider. Repeated efforts, alternate stretching and contraction of the body, push the cone further and further inside. 87 Miyairi and Suzuki were uncertain how each miracidium lost its ciliar y covering but noted that the larvae tended to congregate in the gills, the wall of the digestive organ, the salivary glands and near the nerves. The parasites then became immobile and transformed in to small, spherical sporocysts which grew daily. By twelve days after infection, Miyairi and Suzuki found secon d generation sporocysts (they called them rediae) within the primary sporocysts: the redia is a strange animal which, in open movement, can stretch out then contract again into an oval form....Its head is thickly covered with fine spines. The mouth is often wide open as though the animal intended to bite something. Very little can be seen of the digestive tract. The entire abdominal content consists of rather large, pale cells which, in the course of time, divide to form large and small cell aggregates. 87 The secondary sporocysts migrated into the liver where they grew lengthwise. Seven weeks after infection of the snails, Miyairi and Suzuki found cercariae within the secondary sporocysts. They wrote that "a cercaria is provided with a powerful caudal tail and this is split, in its distal third, into two parts. Th e body and the caudal tail are covered with spines" 87. then went on to provid e details of the anatomical organization of the cercaria. The next step was to complete the life cycle of the worm by infecting mice with these cercariae. Attempts to infect mice with cercariae raised in snails in the laboratory were unsuccessful, so Miyairi and Suzuki used older, naturallyinfected molluscs. These snails had three types of cercariae, one of whic h 272 A History of Human Helminthology resembled those raised in laboratory snails exposed experimentally to S. japonicum miracidia. A mouse was placed together with the snails for three hours each day for three days. Three weeks later, the mouse was killed by anothe r mouse, but on examination, the investigators found male and female schist osomes in its internal organs. This experiment was repeated on a number o f occasions with more mice, and they were always found to be infected. Thus, Miyairi and Suzuki were able to demonstrate that a certain species of mollusc was naturally infected with the larval stages of a worm which matured into adult S. japonicum in experimental mice. Further, they were able to infect clean snails with miracidia obtained from S. japonicum eggs and produce these same larval forms. Although they did not complete the whole life cycle with the same worms under laboratory conditions, there was nevertheless no doubt that Miyairi and Suzuki had found an intermediate host and had described th e various stages of metamorphosis and reprod uction of larval S. japonicum. They were unable to identify the snails exactly, but concluded that the mollusc s probably belonged to the family Hydrobiidae, remarking that precise species identification must be left to the specialist. At the same time as Miyairi and Suzuki were ca rrying out their studies, Miyagawa was working independently on the same prob lem. By a series of exclusion experiments, he identified in snails the fork-tailed cercariae which developed into adult schistosomes in experimental animals. Moreover, he demonstrated the much closer morphological relationship between these latter two stages of the parasite than between the miracidium and the cercariae 81-83. It has been remarked that Miyairi received none of the international honours he deserved89, but the same cannot be said, on this occasion at least, for Robert Leiper. On 20 February 1914, Leiper and Staff Surgeon Edward Atkinson of the Royal Navy left London for eastern Asia accompanied by an editoria l fanfare in the Journal of Tropical Medicine and Hygiene : The departure of the expedition....is an event which must prove of considerable scientific importance....The primary object of the expedition is to ascertain the mode of spread of the trematode diseases of man.3 Leiper and Atkinson arrived in Shanghai at the end of March and were granted good laboratory facilities. This site had the added advantage of providing them with ready access by road and water to endemic areas of schistosomiasis. They investigated a number of parasites including Clonorchis, Metagonimus, Diphyllobothrium, Echinochasma, Metorchis, Fasciolopsis and Ancylostoma, but their main attention was centred on S. japonicum 61. Their first objective was to find a patient with schistosomiasis who could provide them with a steady source of eggs for experiments, but despite travelling 1,000 miles b y boat, train and rickshaw over the space of three months, they failed to find a suitable and cooperative person. By this time, unfortunately, the two principal players, Leiper and Atkinson, had fallen out. Nelson, in his entertaining review of this affair, quotes passages of letters written by Atkinson to Cherry-Garrard, Most of the mice died before Hong Kong was reached. however. on t he parasites that Atkinson had brought back from Antarctica may have started the row between the tw o parasitologists 89.63 It has been suggested that one of Atkinson's main quarrels with Leiper was over scientific priority. an experiment which they termed th e "blunderbuss method". This led Leiper and Atkinson to conclude in their report published in January 1915: The marked attraction of the mollusc for the miracidium. male and female worms in copula were found in the portal vessels at autopsy i n London. he tested the snails with S. showed an extraordinarily marke d attraction for the miracidia.Schistosomiasis japonica a zoologist who was to have worked with them: 273 I don't really think old chap that you can fully realise how perfectly damnable this man can be. japonicum eggs. Leiper an d Atkinson found the liver of these snails "ramified with long intertwinin g delicate tubes bluntly rounded at the extremities and containing cercariae with bifid tails"63. Leiper set off for Japan where he first visited Fujinami. the same as that of Miyairi and Suzuki. the faeces of which were loaded with S. They used miracidia hatched from these eggs to infect all the available local snails. a single male schistosome was found. the peculiar morphological characters of the cercaria and the successful infection of a laboratory-bred mouse from cercariae obtained from Katayama molluscs after several weeks' captivity at sea leave no room for doubt that the schistosome has a life-cycle similar to that of other trematodes. Impatient with the tardiness of their progress. They believed that these tubes were not rediae but secondar y sporocysts. This snail was identified subsequently by G C Robson of the British Museum as a species of a new genus of hydrobii d mollusc which he named Katayama nosophora 95. None of the molluscs. were attractive to the larvae. but sufficient survived to provide cercaria e with which to infect laboratory-bred mice. World War I had b roken out. Many died on the return journey . then journeyed to Katayama and collected a batch of snails to take back with him to Shanghai. Encouraged by this success. with Leiper as senior author. however. Atkinson may have felt that Leiper gave insufficient credit to the pioneering work of the Japanese scientists with inadequat e . On his return to China. the few remaining snails were sacrificed and used to infect the last remaining mouse. At Aden. Furthermore. so the expedition was aborted and Leiper and Atkinson returned to Britain with their specimens. Nelson has postulated that the publication of tw o papers. One month later.5 In the event. but in one putrescent animal. I ought to give him a sound thrashing. tell him what he is for the good of his soul and then leave him. from a customs officer in Yanchow. This fellow has really been too damnable for words. Meanwhile. Leiper returned to Katayama an d collected another supply of these molluscs. Similarly. Leiper and Atkin son gave up their search for infected humans and borrowed a dog. japonicum miracidia and found that one species. 63 Nelson has written that it must have been a great shock to Leiper when h e visited Fujinami in Japan and the latter revealed to him the full details of th e work of Miyairi and Suzuki. for three years later. haematobium) within practical limits. Concerning Miyairi and Suzuki's work.274 A History of Human Helminthology reference to them in his publications.62 This morphological clue. Finally. for adult schistosomes. In the Tropical Diseases Bulletin of March 1914 (p. in their paper of January 191 5 (which was probably written largely if not entirely by Leiper as Atkinson was on active service). there is only a sketchy outline of the Japanese discoveries and no specific references are given. than he let on. he suspected.. Unfortunately. no ment ion at all was made of the Japanese studies among the 532 references on schistosomiasis that Leiper published in 1915 i n connection with his studies of the life cycle of S. the preceding abstract. It seems quite likely. this abstract was referred to with the words "see above" in the text of Leiper' s abstract (although it is possible that the comment was inserted in an editorial capacity by someone else). he harked back to his Japanese experience and took some pains t o emphasize what he then felt had been his main contribution and the guidin g principle behind the establishment of the expedition to the East: a morphological clue might be established by which the bulk of cercariae of unknown origin could be excluded microscopically. prepared by Fleet Surgeon Kumagawa of the Tokyo Naval Medical College. and reiterated the . 1914. however. Leiper may have been stung by such complaints as those attributed to Atkinson. haematobium. and he then went on to acknowledge the work o f Miyairi and Suzuki (but. that Leiper knew more about this work. Further.. again. it seems inconceivable that he did not know of it s publication. even bef ore he left for the Far East. Indeed.. his paper is inaccessible. thus bringing the experimental use of monkeys (for infection with S. Leiper in the 1915 paper with Atkinso n made no mention of the German version of Miyairi and Suzuki's pape r published in 191487. haematobium in Egypt. Leiper provided a n abstract of the paper by Katsurada of December 1913 in which Miyairi an d Suzuki's work is alluded to. More imp ortantly. might be the absence of a muscula r pharynx in schistosome cercariae compared w ith cercariae of most other flukes. wa s concerned with Miyairi and Suzuki's definitive paper written in Japanese. Miyairi of Kiushu had just found a reproductive stage of Schistosoma in a Lymnaeus species"63. 290). it is merely recorded that there is a note in a paper by Katsurada in December 1913 "to the effect that he is informed in a private letter from a colleague that Mr.The only information at present available to workers is an annotation by Kumagawa in the Tropical Diseases Bulletin for March 30th. the paper concludes: It would appear that the above results confirm Miyairi's main conclusion as to the transmission of Schistosoma japonicum. particularly as he had discussed the Japanese investigators ' observations with Fujinami who would have known of its imminent or actual publication. without giving a reference). Thus. In this surmise Leiper was right. in the final part of his report on his studies of S. in contrast to these trematodes. had no pharynx. O. adult schistosomes were found in a pig in Taiwan. Japan. Michigan. if not identical. Eighteen days later.. zoophilic strain wh ich develops for a short period in the viscera of humans but does not reach maturity 42. In August 1922. japonicum of Japanese origin 27.. pigs. My own observations therefore confirmed generally the results of these workers. Fa ust and Meleney therefore postulated that the same or a similar species of mollusc must be the intermediate host in China. and cattle. he killed the animal and recovered young schistosomes 5 mm long from the portal venous system 122. apart from establishing my chief. goats.had succeeded by another method of approach in tracing the metamorphosis in a closely allied. japonicum adult worms were eventually obtained 78. Another batch of snails which was not naturally infected was infected under experimental conditions with S. including Viviparus. however. In February 1914. in an appendix to Faust and Meleney's monograph o n schistosomiasis japonica which appeared in 1924. Cercariae. When dissected in the hospital laboratory. from S Yoshida in Osaka. Planorbis and Lymnaea species could not be infected. 28% of these snails (which were identified subsequently as Oncomelania (Hemibia) hupensis by Bryant Walker of Detroit. obtained the cercariae and rubbed them on to the skin of a rabbit. Attention then turned to China when Faust and Meleney investigated schistosomiasis and its transmission on the Chinese mainland. In February 1922.Schistosomiasis japonica 275 importance of the morphology of the cercaria for his own studies of the lif e cycle of S. then subsequent surveys disc losed them in dogs. ulterior object. Many years later. japonicum was then confirmed in another geographical area by S. japonicum in the Philippines 111. Nelson Annandale of th e . Meleney found some similar snails near Soochow in the lower Chang Jiang (Yangtze) Valley on river banks near the water's edge and on water grass stalks. Eventually he succeeded in finding an infected snail. Miyairi and Suzuki. Their first step was to obtain some snail vectors.62 The life cycle of S. Meanwhile. USA) contained schistosome cercariae. known at that time as Blanfordia nosophora . they showed that these snail s were susceptible to S. which were produced nine weeks afte r exposure of the snails. Tubangui demonstrated that a snail identified by J Bequaert o f Harvard University as Blanfordia quadrasi (now known as Oncomelania quadrasi) was the intermediate host of S. which was to provide a simple and reliable means of attacking the complex problems of B. haematobium: In the meantime. Yokogawa therefore collected snails and examined them for cercaria e resembling those described by Miyairi. japonicum miracidia of Chinese origin and the metamorphoses of the larvae were observed.. These cercariae were then used to infect laboratory mice and S. japonicum miracidia from a Chinese patient whereas the usual molluscs in the Peking area. In 1932. snail in the South Island of Japan. japonicum is a non-human. Yokogawa. hupensis was infected successfully with S. Hsü and Hs ü showed with human volunteers that the Formosan strain of S. were used to infect experimental dogs 28. haematobia. Finally. had reviewed the status of the molluscan intermediate hosts of S. and determining the structures of the various developmental forms. Two schools of thought then arose as to the means by which worms reached the portal system from the lungs. Narabayashi proposed that the parasite s entered the pleural space then passed through the diaphragm to the liver and portal circulation 88.276 A History of Human Helminthology Zoological Survey of India and the Indian Museum. were immersed in water in areas where the disease was rampant. Calcutta. then he collected blood between two and twenty four hours later. He applied cercariae to the skin of experimental animals and observed thei r passage through the integument via the bloodstream to the lungs 91. He went to Yamanashi province of Japan in the summer of 1911. especially dogs and rabbits. Miyagawa managed to find schistosomula. STUDIES OF THE MIGRATION AND DEVELOPMENT OF LARVAE Once Fujinami. which was quite distinct from the genus Blanfordia 2. that S. He was supported in this view by Suyeyasu who studie d serial sections of mice 104. formosana and hupensis. then entered the vascular system and possibly the lymphatics. nosophora. Initially. Soon afterwards. he looked for worms in the portal venous blood. Yoneji Miyagawa turn ed his attention to both tracing the route of migration of the worms from the skin to the portal venous system. Nakamura and others had shown that infection was acquired by the percutaneous route. This led him to conclude (before Miyair i and Suzuki's proof) that the change in appearance must have occurred in a n intermediate host: On comparing the youngest described worms with the miracidia originating from eggs. all of which belonged to the genus Oncomelania Gredler 1881.81 In a subsequent study. He concluded that there were three species which transmitted the worm. He examined the anatomy of these skin worms in detail and compared them with adult worms in the portal vein and free-living miracidia. therefore. and found that they resembled adul t schistosomes more than miracidia. and were carried to the portal veins. he believed tha t most worms passed directly via the bloodstream 82. Experimental animals. Miyagawa reported that he had found schistomula i n thoracic duct lymph of infected dogs and in the draining lymph nodes. Ogat a made use of Miyairi and Suzuki's discovery t o confirm Miyagawa's findings. but Miyagawa and Takemoto contended tha t schistomula left the lungs via the systemic arterial circulation and were carried to the gastrointestinal tract where they then found their way to the porta l . japonicum very probably has an intermediate host. He then identified similar worms in the skin and concluded that they had penetrated the skin partly directly an d partly via the hair follicles. japonicum. however. Because of the paucity of numbers of worms in the lymph. I found a considerable difference. In these samples. I assume. Schistosomiasis japonica 277 venules. Miyagawa and Takemoto based this view on their failure to fin d worms penetrating the diaphragm or in the liver parenchyma, wherea s parasites were seen in the intr ahepatic blood vessels of experimentally infected animals84. Shortly thereafter, Cort examined the development of these worms in detail. He noted that soon after penetrating the skin, the tail of the cercaria was los t and the cephalic glands dege nerated. By the twelfth day, the majority of worms had reached the liver. There was little increase in size until the larvae reached this organ, although the digestive system became more organized and the oral sucker assumed its adult character. Cort was unable to distinguish between the sexes in the earliest liver stages, but began to discern differences when the y reached 0.3-0.4 mm in length. Growth continued after sexual maturity but at a slower rate. As growth continued, he observed that the body of th e female worms became rounded on cross-section while that of the male worms flattened gradually and the sides grew up to form the gynaecophoric canal. Pari passu with these events, the suckers grew and the digestive system becam e horse-shoe shaped and distended with food. Differentiation of th e reproductive organs came relatively late and they only became clearl y distinguishable when the male and female worms attained lengths of 1.5 an d 2.0 mm, respectively 22. A year or two later, Meleney and Faust re-examined both of these aspects . They observed the process of invasion by cerca riae, noting that during invasion, if not before, the tail of the organism dropped off, and determined that invasion might be effected within several hours but could take up to two days. Within two to three days of exposure of e xperimental animals, most schistosomula had reached the lungs. Although a few worm s were side-tracked in heavy infections and reached the pleural cavity where they degenerated, most larvae passe d through the lungs into the systemic circulation. Meleney and Faust agreed with Miyagawa's contention, for they recovered worms at this stage of the infection, not only from mesenteric artery, but also from the renal, splenic and a variety of peripheral arteries79. They found that those worms which reached the portal venous system were able to grow and develop, with sexual differentiatio n occurring as early as the seventeenth day, although sexual maturity was no t reached until after four weeks. By this time, the worms had migrated retrograde from the liver to the distal mesenteric venules where they laid eggs 28,29. In 1932, Goto attempted to settle the argument over the two routes of migration. He found that washing out of the organs and tissues of dogs infected with S. japonicum supported the systemic arterial migration theory of Miyagawa and Takemoto while serial sections of decalcified mice indicated direct migration as espoused by Narabayashi and Suyeyasu. Consequently, Goto concluded that the results obtained depended upon the technique used 39. Once within the portal system, worms may live for many years, continuing 40 infections being reported 32 years 76 and 47 years after the last possible 278 exposure. A History of Human Helminthology CORRELATION OF INFECTION WITH PATHOLOGY The pathological changes produced by S. japonicum were recognized by Majima simultaneously with his discovery of the eggs in 1888. The gros s morbid anatomical changes he found have already been alluded to, as has his description of the ova. In addition, however, Majima provided a luci d exposition of the histological appearances, emphasizing that the eggs occurred only in the portal tracts and not within the lobules, discussing the inflammatory infiltration, and remarking upon the interlobular fibrosis: these parasite eggs....were in peculiar locations in the connective tissues, mostly with great numbers of eggs in large groups. Around the ends of these groups of eggs....a marked infiltration of round cells was observed....There were indications in various places of a new interlobular connective tissue; in these areas with increased interlobular connective tissue there was marked round cell infiltration as well as swelling and proliferation of the bile ducts....Because of the pressure by the new connective tissue, atrophy was seen likewise in a small number of cells. 72 Katsurada in 1904 described the pathological consequences of infection in both the liver and intestine, and remarked upon the absence of lesions in th e rectum. He concluded that female worms released eggs which embolized t o several organs where they excited inflammation and fibrotic reactions. Wit h respect to the liver, he wrote: "In consequence of this the liver sooner or later shrinks, and a kind of cirrhosis results, whereby the capsule of the live r becomes granular, thickened and irregular" 50 and concerning the bowel , Katsurada remarked: in most cases, eggs are found in the intestinal mucosa and submucosa, especially in the large intestine. The deposition of eggs induces more or less severe inflammation, which leads in parts to tissue disturbance, in parts to tissue growth; infiltration in the bowel wall follows, and that frequently terminates in ulceration of the mucous membrane.50 These features were reiterated by Catto who described deposition of ova, not only in the liver and large intestine, but also in the gall bladder, mesentery and small bowel, and wrote that "Where ova accumulate they provoke at certai n places a small-celled infiltration, wh ich gives place later to a great proliferation of fibrous tissue" 17. In 1924, Faust and Meleney reviewed the p athological anatomy 29. They noted that the invading cercariae produced a local reaction in the skin characterized histologically by oedema, congestion and leucocytic infiltration. In thei r passage through the lungs and later i n the gut, the chief lesions produced by the young worms were haemorrhages. In massive infections, there was hepati c parenchymal cell necrosis and degeneration of the convoluted tubules of th e kidneys, presumably as a result of released toxins. Polymorphonuclea r Schistosomiasis japonica 279 leucocytes, and particularly eosino phils, congregated around eggs in the tissues and abscesses formed; these tended to break outwards by small openings into the intestinal mucosa. Thrombosis of the lar ger mesenteric and portal veins was frequently seen in later cases. In the liver, there was, in addition to th e inflammatory lesions produced by degeneration of eggs, a general pipeste m fibrosis. The spleen varied in size, but was sometimes hypertrophie d enormously. Faust and Meleney were unimpressed by lung lesions, but noted that eggs might sometimes be seen in the brain. RECOGNITION OF THE CLINICAL FEATURES Japanese clinicians became aware gradually of a syndrome characterized b y hepatosplenomegaly, diarrhoea, anorexia, gen eralized oedema and anaemia that was endemic in certain parts of the country. It was particularly prevalent in a village named Katayama, and was, on that ac count, sometimes known as Katayama disease, the villagers ascribing the condition to a lacqueur said to hav e been released from a ship wrecked nearby in a storm years before. The first recorded clinical description of schistosomiasis was by a physician, Dairo Fujii (pen name, Yoshinao), who visited the region in 1847 and wrote a report which remained largely unknown for man y years. It was eventually found in the possession of a descenda nt, Yaekichi Fujii, and Fujinami arranged for its publication. Fujii did not know what type of disease it was, but described the initial cutaneous manifestations, considered the onset as being not unlike that of consumption (wasting disease, tuberculosis, although that infection was not yet defined bacteriologically), and concluded that in its terminal stages, th e condition was really an "abdominal swelling": the native people who waded in the water to till the fields developed on their lower legs small papules which were extremely pruritic....the clinical manifestations in severe cases - pallor, sunken yellow facies, night sweats with muscle wasting, a rapid and feeble pulse - were similar to those of consumption. Some people had watery diarrhea and some had tenesmus. Others had a bloody or mucoid diarhhea. Later wasting of the extremities occurred and the abdomen became swollen, like a drum. Below the breasts the abdominal veins were dilated and the umbilicus herniated outward. In advanced cases, the abdominal skin became shiny, even reflective, anasarca usually ensued and the patient died.32 In the early 1880's, Erwin Baelz, a German professor at the Imperia l University of Tokyo, visited the endemic area at Okayama. He found that 20% of the population were afflicted with hepatosplenomegaly, bloody diarrhoea , anaemia, fever, ascites and oedema. Baelz attributed these findings t o Clonorchis sinensis 6, although it now seems much more likely that he wa s dealing with schistosomiasis japonica. Nearly sixty years after Fujii's visit, and being aware of his memoir, Kenj i Kawanishi (Kasai) visited Katayama. He too was familiar with the skin rashes, 280 A History of Human Helminthology and noted that cows and horses were also affected, writing "Persons who g o into the mud immediately develop red rashes; the associated pruritis (sic) i s said to be unbearable" 52. He then went on to state that the signs of Katayam a disease were "(an) enlarged liver and spleen, sometimes abdominal ascites , anaemia and bloody stools" 52. Although the relationship betwen schistosomiasis japonica and skin rashes was fairly striking, there were some dissenters. For example, Miyagawa (1913) discounted the association on a number of grounds, including variations i n geographical distribution of the two conditions, differences in the histological appearances of the skin, and the absence of eggs in the faeces of many patients with dermatitis 83. In various parts of China, a syndrome of fever with urticaria had been recognized from time to time. This condition was known as Yangtze Fever, Hankow Fever, Kiukang Fever and Urticarial Fever, dep ending upon the region in which it was observed. In 1910, Houghton at Wuhu Hospital in China associated this syndrome with S. japonicum infection69, then this opinion was supported b y other observers. In 1913, Edgar gave an excellent description of the syndrome which usually afflicted children or young men who bathed in creeks or waded in marshy ground in the Chang Jiang (Yangtse) valley; the condition wa s particularly well-recognized in foreign seamen. According to Edgar, malaise was followed by headache, myalgia and fever which was remittent in character and lasted for three to six weeks. Half of the cases had transient or persistent urticaria, and many complained of cough and transitory diarrhoea whic h sometimes developed into dysentery. The illness usually settled down withi n two to three weeks 26. This description was reiterated in the following year by Laning wh o described two further stages in the evolution of the disease 56, a classification which was also adopted by Mann 73. The next stage of illness was associate d with hepatosplenomegaly, dysentery, marked eosinophilia, and the passage of S. japonicum eggs in the stools. A terminal stage which may or may no t supervene was typified by a: cirrhotic liver, sometimes enlarged, sometimes shrunken, ascites, oedematous extremities, marked emaciation, anaemia, weakness, passage of blood and mucus in the stools.56 Interest in the clinical manifestations of schistosomiasis japonica by Western clinicians was rekindled when a number of troops became infected during the invasion of Leyte island in the Philippines in 1944. A number of series o f patients were reported, and these descriptions generally followed the patter n described thirty years earlier in China 30,45,107 With respect to prognosis, it had been apparent from the early times that the severity of illness seemed to be dependent upon the intensity of infection. Longterm observations of expatriates infected in China before and around Worl d War I, and of Allied troops infected in Southe ast Asia during World War II, and who were then removed from the endemic area, indicated that the prognosi s Schistosomiasis japonica 281 was probably good in the absence of reinfection. Whether or not significan t resistance to reinfection develops is uncertain, although Vogel and Minning in 1953 reported that complete resistance to reinfection could be built up i n experimental monkeys infected repeatedly with S. japonicum 116. DEVELOPMENT OF DIAGNOSTIC METHODS The simplest means of diagnosing schistosomiasis japonica, that is the demonstration of the pathognomonic eggs in the stool, was discovered before th e causative agent was found. Thus, in late 1902, or possibly in early 1903 , Kawanishi discovered what he regarded as a new type of egg in the faeces of a patient from near Katayama. This patient had the typical syndrome common in that area: In the stools.....I found oval-shaped light brown colored eggs, 0.1-0.08 mm in length and 0.077-0.05 in width.....an operculum is not found. The eggs vary in content. 52 Kawanishi therefore went back to the endemic area in March 1903 and found several more patients excreting the same eggs. The value of this diagnosti c technique was confirmed by Katsurada 49,50 in 1904 when he found eggs in the faeces of five such patients and then went o n to discover the adult worms. Since that time, considerable attention has been paid to improving techniques fo r demonstrating and quantifying eggs in faeces (see chapter 9). The introduction of sigmoidoscopy provided a means of assessing structural damage to the large bowel and permi tted an alternative method of finding eggs. Thus, Johnson and Berry (1945) reported that small yellow nodular lesion s could be seen on sigmoidoscopy, particularly at the rectosigmoid junction, and that biopsy of these lesions revealed the presence of the characteristic eggs 45. Diagnosis of schistosomiasis japonica by liver biopsy, which also provides an assessment of structural damage in the live r, appears to have been first reported by Stransky and Pesigan in 1953 101. Later, Kurata showed that liver functio n tests may provide an index of hepatic damage 54. Many attempts have been made to dev elop immunodiagnostic procedures for use in schistosomiasis japonica. In 1910, Yoshimoto was probably the firs t person to introduce a complement fixation assay 123, while Miyairi and Imai in 1928 described a precipitin test 85. In 1936, Kan described an intradermal test 46. THE SEARCH FOR EFFECTIVE TREATMENT Details of the development of drugs which have been used in the therapy o f schistosomiasis japonica have been described in chapter 8. Initially, quinine 110 and arsenicals were tried, particula rly in Japan, but these drugs did not pass the test of time and proved of little use. In 1913, Hutcheson reported that emetine 282 A History of Human Helminthology was useful in patients with dysentery 43. In view of the efficacy claimed for the drug in other forms of schistosomiasis, there may have been some activit y against S. japonicum, but it is also possible that the patients had concurren t amoebic dysentery which responded to the drug. There was dispute over th e effectiveness of emetine during the next few years 51,94,112, but interest in it largely waned in favour of tartar emetic. Following the introduction of antimonials for the treatment of schistosomiasis in Africa, the drug was tried in Chin a and Japan against S. japonicum. In 1921, Sanders and Priston reported that intravenous injection of antimony was efficacious in three patients; there was a great reduction in the numbers of ov a excreted and those that were present in the faeces were not viable 97. On the other hand, Libby, in a small series of cases, found that tartar emetic was not particularly active and this led to suggestions that this drug was less effective in schistosomiasis japonica than in other forms of human schistosomiasis 65. In a later and more extensive study, the same author concluded that while tartar emetic was useful in mild and moderate cases, it was of little value for patients with severe infections where there was hepatosplenomegaly 66. Nevertheless, Meleney and his colleagues regarded the drug as curative when a total dose of 1.5-2.0 grams of antimony was given over a period of 18-20 days 29,80. Moreover, Nishi investigated the actions of the drug in experimentally infected dogs and found that sodium antimony tartrate was able to kill youn g schistosomes and affected eggs in tissues 90. In 1951, Pesigan and his colleagues showed that lucanthone, when used in doses recommended for other forms of schistosomiasis, was ineffective in the treatment of S. japonicum infections93. Likewise, metrifonate and oxamniquine were found to be inactive. At a symposium on niridazole held in Lisbon i n 1965, there were suggestions that this drug may be less effective i n schistosomiasis japonica than in the treatment of S. mansoni and S. haematobium infections. This question was investigated further by Santos and hi s colleagues in the Philippines; they found that the cure rate in 106 patient s treated with various regimens of niridaz ole ranged between 48% and 85% 98. Sy then treated 237 persons and managed to follow up just over half of them one month later; 55% were cured, the egg count wa s reduced in 18%, and there was no response in the remaining 27% of patients 105. Praziquantel now looks to be the drug of choice in the treatment of schistosomiasis japonica. Th e introduction of this drug has been described in chapter 8. Suffice it to say here that Santos and his colleagues studied the effects of different dosage regimens in 128 Filipino patients and found that praziquantel was very effective; onl y 24% of patients treated for three days and reviewed 12 months later were still passing ova in the faeces 99. Schistosomiasis japonica 283 UNDERSTANDING THE EPIDEMIOLOGY The syndrome known as Katayama disease and w hich turned out to be caused by S. japonicum, was associated with water long before the causative agent was identified. Thus, Fujii in 1847 related the condition to wading in the padd y fields, and by making use of the appearance of a rash on the legs, was able to pinpoint the time of the year at which infection was acquired to the seaso n between spring and summer 32. The same connection between working in rice fields and Katayama disease was recognized by Kawanishi who, in 1904 , provided a concise description of the locale. At that time, Katayama was a village of 190 inhabitants and 36 houses situated at the foot of a hill 80 fee t high. The paddy fields were several feet lower than the level of the river, thus making it very difficult to drain the stagnant water, particularly during th e prolonged rainy season, and it was in these fields that workers developed the erythematous eruption on their legs 52. Furthermore, it was in these people that Kawanishi found S. japonicum eggs, thus bringing the nature of the affliction closer to clarification. Fujii also recognized the focal nature of the condition, the locations an d boundaries of which were gradually extended by a number of Japanes e clinicians over the next sixty years. The discoveries by Catto in 1904 o f S. japonicum in a man from Fukien province of China16,17, and in an 18 year old male in Hunan province, China, by Logan in the following year 68 widened knowledge of the geographical distribution considerably, as did the report by Wooley in 1906 of schistosomiasis japonica in the Philippines 118. Many years later (1937), Brug and Tesch discovered an endemic focus of infection i n Sulawesi, Indonesia12. From time to time, weather conditions led to epidemics of schistosomiasis in new areas as, for example, occurred when the summe r floods in the Chang Jiang (Yangtse) valley in 1931 brought the infection from the upper part of the system down to the delta 47, or when major floods occurred in China in 1954 67. The reason for the association with water fell into place, of course, with the discovery that certain species of snails were the vectors of infections. Attention then turned to investigating the behaviour and ecology of these long, narrow, operculated snails. The amphibious snails were most numerous in wet, moist soil near water and thick grass. The population was densest along irrigatio n ditches and became progressively thinner on the banks of rivers and canals, in rice beds, and in paddy fields. It was shown that they were most active at night, but crawled only at a rate of about three metres a month. If the surface of the earth became dry, the snails dug down into the deeper, wetter reaches, and by closing the operculum, survived for three months or so, although infecte d molluscs tended to die earlier. Mating was found to occur throughout the year, but was at a maximum in the spri ng and early summer and at a minimum in the early winter, with many snails hibernating during the depths of winter. Th e average life span was determined at around five years or so, wit h 284 A History of Human Helminthology newly-hatched snails taking up to a year to reach maturity 21,29,103. Finally, it was realized from the beginning that this form of schistosomiasis was an extensive zoonosis, for a wide range of animals were found to b e infected in nature, beginning with Katsurada's discovery of adult worms in cats in 190449,50. These included dogs, rats, mice, cattle, water buffalo, pigs, horses, sheep and goats. THE EVOLUTION OF PREVENTIVE AND CONTROL MEASURES Hopes for the control or, better, the eradication of schistosomiasis have been held for many years. Over a century ago, Fujii left a memoir expressing thi s desire: I recently read my manuscripts and found the script of 'Katayama Memoir'. Thirty years have passed....By knowing (what causes it), we can treat it. In this way, the mysterious disease which has existed for many years can be eliminated easily. This would be good for the people.32 Once Fujinami and Nakamura had shown that infection was acquired whe n parasites penetrated the skin , they were able to suggest several means whereby the infection could be contained: (1) the faeces which contain the eggs must be disinfected. (2) in order to prevent the growth of the causative agent, constructions on land and water must be renovated; (3) in order to prevent the causative agents penetrating the body, contact with contaminated water should be avoided.36 The first of these points was overvalued to some extent, for it took no account of the excretion of eggs by infect ed animals, while the last proposal was clearly impossible for the many peasants whose livelihood depended upon working in the paddy fields. The discovery of the snail intermediate host by Miyairi an d Suzuki, however, provided another point at which the cycle of transmissio n could be attacked. This seemed the simplest approach, so attention in Japa n centred upon the evaluation of various molluscicides. Of all the chemical s tested, lime was found to be the surest and most economical agent 34,37. This chemical was available readily in Japan and the farmers used it for fertilizing the rice fields. Lime was therefore spread on the banks of infested canals and drainage ditches, and in the water contained in them. Alternatively, Fujinami and Fukutuni showed that burying the snails in wet, but not dry, soil kille d them. In 1928, Todokoro reported on the effectiveness of a combination o f measures in Hiroshima prefecture in Japan. These included the destruction of snails with lime, the installation of pit latrines, the replacement of cattle b y horses (which are less susceptible to infection 34) for ploughing, the repression of wild rats, and educating the local inhabitants about the dangers of immersing skin in water. The results were highly encouraging, with the incidence of skin rashes decreasing and the prevalence of infection in cattle and the numbers of Schistosomiasis japonica 285 snails dropping markedly 108. Since that time, and occurring pari passu with improving economic conditions, as well as the introduction of specifi c measures such as the cement lining of irrigation ditches and the availability of more effective molluscicides, the infection has almost disappeared i n Japan120,121. Similar excellent results have not been achieved in the Philippines o r Indonesia where the paucity of economic resources has militated agains t attempts to control the infection. The situation in China is somewhat less clear. In 1924, after reviewing the biological and technical problems in volved, Faust canvassed some of the social and political factors that would affect control measures: One more fact must be kept in mind in considering such an undertaking so intimately concerning the native farming class - namely, their suspicion that only harm can result from any stranger tresspassing on their domain. Coupled with this is the improbability of securing any government cooperation at the present time in China. 27 Then, with truly prophetic foresight, he went on to add: In spite of these unpleasant facts, the problem of eradicating schistosomiasis from China is a hopeful one. One must bear in mind that China is an ancient country, that she moves slowly and deliberately, but that she moves surely. The next fifty years will bring much in the way of reorganization and development in China. It seems not too much to expect that public health and preventive medicine will follow closely upon the steps of improved agriculture and commerce, and that in this scheme of affairs, schistosomiasis will not long be allowed to remain an uncontrolled infection in the heart of the country.27 Schistosomiasis was regarded in China as a serious parasitic disease with a major economic impact. By the middle of the 1950's, a nationwide contro l scheme was evolved and put into operation. Maegraith visited the country a year or two after the inititiation of this programme and has recorded hi s impressions 71. The extent of infection at that time was not fully known, but it was estimated that over 11 million people were infected in the fertile region of the Yangtse valley. The three major components of the control scheme wer e mass treatment of overt infections (with the two-fold aim of bringing clinical relief and a reduction in the contamination of the environment with eggs) , preventing the pollution of water by infected human and animal faeces, an d destruction of the snail intermediate hosts. Schistosomiasis centres wer e established for the purpose of mass treatment, propaganda and administrative control, while the actual field work was done by local farming and villag e communities. The year 1970 was set as the target for effective control. Th e most commonly used anthelmintic was sodium or potassium antimony tartrate, given intravenously, initially in seven or 20 day courses, but later in a three day regimen of treatment. Educational campaigns were set up to limit promiscuous defaecation; arrangements were made to collect and store faeces for one week in order to allow the ammonia that was generated to destroy the ova whic h otherwise would survive for several months, but problems were encountered in dealing with animal faeces. Snail control with molluscicides was instituted 286 A History of Human Helminthology with Paris green or calcium arsenate being used most commonly at first, bu t later sodium pentachlorophenate be came the most popular chemical; they were sprayed on land within two metres of the water level. Physical methods were also employed; these included burning of grass in summer and the manua l removal and burial of snail-containing mud in winter. In 1977, an American delegation visited China in order to assess the impact of these various measures on the prevalence of schistosomiasis 4. The members of the delegation noted that by 1959, 25,000 communal health units concerned with schistosomiasis control had been set up. Between 1958 and 1962 , 5,000,000 people were treat ed with schistosomicides. The campaign to reduce the numbers of Oncomelania hupensis , however, was the most importan t feature of the control efforts. The delegation considered that there had been a reduction by two thirds in the prevalence of human schistosomiasis. Th e success of the programme was ascribed to China's economic, social an d political organization which permitted disciplined mass participation, a n approach which would be very difficu lt for any other nation to emulate. Finally, it was also concluded that in addition to the effects of the various specifi c control measures, the reduction in schistosomiasis transmission was probably also consequent upon a general improvement in socio-economic conditions. SCHISTOSOME DERMATITIS (SWIMMER'S ITCH, BATHER' S ITCH) Cases of dermatitis of unknown aetiology had occurred for a number of years in persons wading in the freshwater Douglas Lake in Michigan, USA, whil e collecting biological specimens for the Michigan Biological Station. Simila r cases had also occurred in people at several holiday resorts in the region. I n 1928, WW Cort, while collecting molluscs, ( Lymnaea emarginata-angulata ) discovered accidentally that cercariae of a non-human schistosome, Cercaria elvae (now known as the cercaria of Trichobilharzia ocellata ), produced a severe, prickly sensation on the wrists and that this was followed by th e appearance of papules which evolved into a pustular eruption with intens e itching within 48 hours 23. Soon afterwards, Christenson and Greene confirmed this observation a t several lakes in Minnesota, finding C. elvae in Lymnaea stagnalis opressa 20. Later that year, a similar outbreak occurred in people bathing in an artificia l lake in Cardiff, Wales, and this was shown to be due to the same parasite 77. In 1930, Taylor and Baylis pointed out that C. elvae was identical with C. ocellata. They further remarked that although the adult form was not known, the cercariae resembled closely Bilharziella polonica which inhabited the mesenteric veins of ducks 106. This was confirmed in the following year b y Schistosomiasis japonica 287 Brumpt who placed four ducks in a vessel containing C. ocellata then recovered subsequently eggs and adult forms of B. polonica 14. In 1940, Brackett (who had been exposed naturally on many occasions) infected himself deliberately with C. stagnicola and C. ocellata then excised the lesions 29 and 50 hours later, respectively; no cercariae were seen but intense inflammation was noted11. Subsequently, similar cases of dermatitis caused by cercariae o f Trichobilharzia, Gigantobilharzia and Ornithobilharzia species, the definitive hosts being birds and the vectors including species of Chilina, Physa, Planorbis, Polypis and Stagnicola were reported from many parts of the world. A second form of cercarial dermatitis acquired in fresh water was shown to be due to penetration of human skin by cercariae of schistosomes whic h develop in mammals other than man. This was first reported by Buckley i n 1938 who found that dermatitis in workers in paddy fields was a consequence of infection with S. spindale cercariae15. Similar effects have since bee n recognized as being caused by S. bovis 9, S. douthitti 24, S. mattheei 1 Heterobilharzia americana 58 and Orientobilharzia turkestanicum 96. Finally, cercarial dermatitis may also be acquired while bathing in salt water, as was first reported by Penner in 1950. Seabirds serve as the definitive hosts while marine molluscs are the vectors of the worms. Penner described a new avian schistosome larva, Cercaria littorinalinae from the marine snail, Littorina planaxis, found on the coast of southern California 92. Two years later, Stunkard and Hinchcliffe described a s imilar affliction on the beaches of Rhode Island, USA102. Parasites now known to cause this condition include Bilharzia variglandis 102 and Gigantobilharzia huttoni 59. OTHER SPECIES OF SCHISTOSOMA S. BOVIS This species was first described in 1876 by Sonsino when he recovered th e worms from cattle in Egypt100. The eggs are longer and narrower than those of S. haematobium, thus facilitating delineation of the species. Bulinus species are molluscan intermediate hosts. There have been isolated but doubtful reports the occurrence of this worm in humans. S. INCOGNITUM The distinctive eggs of this parasite were recovered from the faeces of tw o human patients by Chandler in 1926. He proposed the name S. incognitum as the parent worms were unknown 18. Later, the adult worms were found in pigs and dogs in India8, then subsequently in rodents in southeast Asia. The egg s have a short, pointed, terminal spine. 288 S. INTERCALATUM A History of Human Helminthology In 1908, GC Low stated that when he was in Uganda, schistosomiasis wa s almost entirely of the intestinal form, yet he only found terminal-spined ova in the stools70. A similar observation was made in 1923 by CC Chesterman in the Belgian Congo (Zaire) 19. In 1934, also in Zaire, AC Fisher found severa l hundred such cases and erected a new species, S. intercalatum, to designate this parasite31. Like S. haematobium, Bulinus species of snails are the intermediate hosts of this worm. It resembles S. haematobium morphologically and may be merely a strain of that helminth. S. MARGREBOWIEI This schistosome was discovered in ruminants by Le Roux in 1933 64. The egg has a small, terminal spine. A human infection was reported by Lapierre and Hien in 1973 57. S. MATTHEEI This schistosome was originally described in a sheep by Veglia and Le Roux in 1929113. The eggs are terminally spined and Bulinus species of snails are the intermediate hosts. The first definitive report of the occurrence of the infection in humans was by Blackie in 1932 following a survey in Southern Rhodesi a (Zimbabwe) 10. S. MEKONGI The first case of human schis tosomiasis of southeast Asian origin was reported in 1957 not from Asia but from Paris when Vic-Dupont and colleagues dis covered the condition in an 18 year old Eurasian with hepatosplenomegaly and haematemesis; the early part of the patient's childhood had been spent o n Khong island in the Mekong river between Laos and Cambodia 114. Between 1963 and 1966, Barbier, also in Paris, saw four more Indochinese students who were infected similarly; enquiry revealed that they had all lived on Khon g island7. Alerted by these observations, a World Health Organization team was sent to the island and found that schistosomiasis was endemic there 44. Subsequent surveys indicated that the infection was endemic in some regions of Thailand. Shortly thereafter, the intermediate host was identified as a n aquatic, not amphibious mollusc, Lithoglyphopsis aperta 41, now known as Tricula aperta 25. In 1978, Voge and her colleagues erected a new species, S. mekongi, for this parasite, on the grounds that the eggs were smaller, th e prepatent period in mice was l onger, and the intermediate host was different 115. Schistosomiasis japonica S. RODHAINI 289 This parasite of African wild rodents was described by Brumpt in 1931 13. The eggs have a subterminal spine. It is transmit ted by Biomphalaria snails. Human infection was reported in Zaire in 1954 by Gillet and Wolfs 38. REFERENCES 1. ALVES W. Experimental cercarial dermatitis in man due to cercariae of Schistosoma mattheei. 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Preliminar y report. Journal of Tropical Medicine and Hygiene 56: 261-266, 1953 STUNKARD HW, HINCHCLIFFE MC. The morpholo and life history of Microbilharzia gy variglandis (Miller and Northrup, 1926), Stunkard and Hinchcliffe, 1951, avia n blood-flukes whose larvae cause "swimmers-itch" of ocean beaches. Journal of Parasitology 38: 248-265, 1952 SUGIURA S. (Studies on the prevention ofschistosomiasis japonica). Mittheilungen aus dem pathologischen Institut der medizinischen Fakultät, Niigata, Japan No. 29, pp 10, 1933. In Japanese, with English summary SUYEYASU Y. (Invasionsweg des Schistosomum japonicum innerholb des Körpers des Wirtes.) Kyoto Igakai Zasshi No. 1: 43-60, 1920. In Japanese, with German summary SY FS. Niridazole in the treatment of schistosomiasis japonica. Journal of the Philippin e Medical Association 53: 151-160, 1977 TAYLOR EL, BAYLIS HA. Observations and experiments on a dermatitis-producin g cercaria and on another cercaria from Limnaea stagnalis in Great Britain. Transactions of the Royal Society of Tropical Medicine and Hygiene 24: 219-244, 1930 TAYLOR HM, GAGE DP. Symptomatology of early schistosomiasis japonica. Bulletin of the United States Army Medical Department 4: 197-202, 1945 TODOKORA K. History of Japanese sc histosomiasis (Katayama Disease) and its prevention in Hiroshima prefecture. Journal of the Public Health Association of Japan 4: 1-9, 1928 TSUCHIYA I. (Yamanishi disease.) Tokyo Iji Shinshi No. 1375, 1904. In Japanese TSUCHIYA I. Clinical, pathological-anatomical, pathogenic, prophylactic and therapeutic study of the schistosomiasis japonica. Sei-i-Kwai Medical Journal 32: 107-109. Abstracted in Tropical Diseases Bulletin 2: 406-407, 1913 TUBANGUI MA. The molluscan intermediate host in the Philippines of the Oriental blood fluke Schistosoma japonicum Katsurada. Philippine Journal of Science 49: 295-304, 1932 TYAU ES. Treatment of Asiatic schistosomiasis. National Medical Journal of China 8 : 83-85, 1922 VEGLIA F, LE ROUX PL. On the morphology of a schistosome (Schistosoma mattheei sp. n.) from the sheep in Cape Province. Fifte enth Annual Report, Director of Veterinary Service, The evolution of a medical literature. WARREN KS. pp 1307. Ueber die Komplementbindungsreaktion bei der Schistosoma-krankheit in Japan. from man and animals.Schistosoma mekongi sp. WOOLEY PG. 1953 117. In Japanese. Southeast Asian Journal of Tropical Medicine and Public Health 7: 137-143. pp 335-346. MINNING W.T. In Japanese. SOUBRANE J. (Eggs of an unknown parasite in the human liver.) Taiwan Igakkai Zasshi 149: 178-183. 1906 119. (Schistosoma japonicum in Formosa.I. Journal of Parasitology 64: 577584. HALLÉ B. 1915.. YOKOGAWA S. Schistosomiasis. YOKOGAWA M. YAMAGIWA K. 1976 121. 1976 122. BRUCKNER D. BRUCE JI. Zeitschrift für Immunitätsforschung 5: 438-445. BERNARD E.) Mittheilungen de r medizinischen Gesellschaft zu Tokyo 4: No. 1890. M. RICHIR C. YOSHIMOTO M. Bulletins et Mémoires de la Société des Hôpitaux de Paris 73: 933-941. Southeast Asian Journal of Tropical Medicine and Public Health 7: 322-329. 1929 114. 1910 . 1957 115. The occurrence of Schistosoma japonicum vel cattoi in the Philippine Islands. 1978 116. VOGEL H.294 A History of Human Helminthology Union of South Africa. Cambridge. 22. Review of prevalence and distribution of schistosomiasis in Japan . 1973 118. with German summary 120. Programme of schistosomiasis control in Japan. Abstracted in 117 123. YOKOGAWA M. Mass. Bilharziose à Schistosoma japonicum à forme hépato-splénique révélée par une grande hématémèse . compared with four geographical strains of Schistosoma japonicum. Press . Philippine Journal of Science 1: 83-89. Über die erworbene Resistenz vonMacacus rhesus gegenüber Schistosoma japonicum. VIC-DUPONT. n. Zeitschrift für Tropenmedizin und Parasitologie 4: 418-505. especially on its intermediate host. VOGE M. and described the pathological changes in the bowel Fujinami found a female worm in the portal vein of a human (May) Tsuchiya found adult worms in cats. then recovered adult worms from mice exposed to cercariae obtained from naturally infected snails 1919 Fujinami controlled the molluscan vectors with lime 1921 Sanders and Priston indicated that tartar emetic may be of some value in treatment 1971 Niridazole was shown to be of value in therapy by Santos and colleagues 1977 Praziquantel was reported to be effective in experimental animals 1979 Praziquantel was shown to be highly effective in humans by Santos and colleagues __________________________________________________________________ . Landmarks in schistosomiasis japonica __________________________________________________________________ 1847 1888 Fujii described the clinical syndrome of Katayama disease Majima found ova now known to be those of S.1. japonicum in human liver and described the pathological appearances 1903 Kawanishi found eggs in human faeces 1904 Kawanishi described hatching of miracidia from eggs Katsurada found male adult worms in the portal vein of a cat (April). then later found male and female worms in another cat. dogs and humans Catto found adult worms in the mesenteric veins of a human and described the pathological appearances 1909 Fujinami and Nakamura showed by experiments with cows that infection was acquired by organisms penetrating the skin 1912 Miyagawa demonstrated schistosomula in histological sections of skin and in blood and lymph 1913 Miyairi and Suzuki described infection of Oncomelania snails with miracidia and the development of miracidia through sporocyst stages to cercariae.Schistosomiasis japonica 295 Table 10. In humans. who had often prepared frogs' legs for eating 125. DICROCOELIASIS DICROCOELIUM DENDRITICUM This parasite was confused with the common liver fluke. Eggs identified as probably those of A. who had eaten baked raccoon 17. USA. He found the worm in an orbital abscess i n a malayan panther (Panthera pardus) which was being kept in a zoo in France 46. Fasciola hepatica. in Ontario. Canada. no t including man. marcianae mesocercariae were removed from the skin of a man.Chapter 11 TREMATODE IMPORTANCE INFECTIONS OF LESSER INFECTION WITH ACHILLURBANIA SPECIES A. NOUVELI This Paragonimus-like fluke was discovered by Dollfus in 1939. an unidentified mesocercaria was observed in the retina of a woman. The life cycle of both of these worms is not well understood. A. In 1973. RECONDITA This fluke was found in the maxillary sinuses of a Brazilian opossu m (Didelphus marsupialis) by Travassos in 1942 135. 297 . the parasite has bee n recovered from a nodule behind the e ar of a ten year old girl in China by Ch'en in 196537. A. A disseminated fatal infection with mesocercariae of A. Snails are the first intermediate host. in Louisiana. americana occurred in 1976 in Ontario in a young man who had eaten inadequately cooked frogs ' legs51. recondita were found in peritoneal granulomas in a 19 year ol d Honduran male16. Finally. INFECTION WITH ALARIA SPECIES Flukes of this genus are found in the intestines of birds and mammals. Cercariae penetrate the skin of a fish or tadpole then move about f reely in the tissues as mesocercariae. dendriticum. In 1952 and 1953. the parasit e thus became known as D. depending upon the geographical region. metamorphosis occurs with two generations of sporocysts being formed and the eventual production o f cercariae. detrita was not the normal host of the worm. then Fasciola dendritica by him in 1819116. Zebrina detrita. vitrina may not be the cercaria of D. detrita and Helicella candidula were infected with von Linstow's cercaria. Many species of land snails act as the first intermediate host . were shown to be the intermediate hosts in the USSR 105. dendriticum. In 1899. dendriticum was not appreciated at that time.298 A History of Human Helminthology for many years. Both investigations wer e based upon intensive epidemiological inves tigations in several heavily infected parts of that country. and that infection of the mammalian host resulted from ingestion of infected ants 70. In 1929. Cercariae of this worm had in fact been seen and labelled Cercaria vitrina by von Linstow in 1887. The eggs are embryonated when passed in the stools. cinerea and F. was heavily parasitized with C. however. COELIA). and he thought it very likely that the latter mollusc might be the intermediate host of D. DICROOS) and (KOILIA. Vogel found that Z. vitrina. The worm is a common parasite in the biliary passages o f sheep. picea. but thei r relationship with D. then raising adult flukes in sheep infected with the cercariae obtained fro m these snails 31. Further searching showed that Torquilla frumentum was host to the same cercaria. Looss transferred the worm to the genus Dicrocoelium erected by Dujardin in 1845 47. Cercariae of Dicrocoelium aggregate in slime balls and are left on the grass as the snail moves along.71. two papers appeared in Germany giving accounts of attempts t o solve the problem of the source of this infection. hepatica or D. meaning double and cavity. The patients described by Bucholz in Germany and Chabert i n France might have been infected with F. deer and other herbivorous and omnivorous animals in many parts of the world. Formica fusca. Krull and Mapes in the US A showed that metacercariae develop in the ant. The same might be said for the nine year old daughter of a shepherd in Bohemia described by Dr Kirchner of Kaplitz and recounted by . this name being derived from the Greek words (DIKROOS. but do not hatch i n water. respectively. W. This was confirmed by Vogel and Falção in Germany 142. It took many years to elucidate the complete life cycle of D. F. Since the distribution of the snail an d dicrocoeliasis did not quite coincide. dendriticum 83. It was named Fasciola lanceolata by Rudolphi in 1803 115. This view was proven to be correct two years later when Cameron infected Helicella by feeding these snails with Dicrocoelium eggs. In another area. dendriticum 139. then the ants. dendriticum (see chapter 4). Nöller found that the snail. When ingested by appropriate land snails. and that its distribution did correlate with the presence of infected sheep 97. he considered that either C. The first description of human infection with this parasite is shrouded i n controversy. or else that Z. in Taiwan in 192992. was described in a human in the USSR by Skrjabin in 1938 126. Later. D. E. Infections of humans have been reported a number of times. in this girl. a probable synonym of E. recurvatum. Since then. respectively. the parasite has been found in humans i n Indonesia and in Egypt. I n 1922. the generic name being derived from the Greek words (ECHINOS) AND (PARYPHE) meaning "spine" and "border". Most of the infections with this parasite have been reported from the USSR 93. but two genuine human cases have been reported from Ghana by Odei 98. Tanabe infected himself experimentally by ingesting cercariae in th e gills of freshwater fish 134. in such patients. The diagnosis is usually made . who named it E. Success has been claimed for thymol and stibophen in the treatment o f dicrocoeliasis121. then Hirasawa recorded a natural human infection 55. koidzunis. by finding the distinctive eggs in the faeces. Many of these cases . paraulum. however. Strom showed in 1927 that they result from the ingestion of liver heavily contaminated with eggs 132. Snails are the first intermediate host and metacercariae encyst in tadpoles and frogs. This uncertainty flows from the difficulty those observers had i n establishing the identity of the adult fluke. HOSPES This species occurs commonly in cattle in Africa. though. A number of spuriou s human infections have been encountered. it was renamed Echinochasma perfoliatus by Dietz in 1910 45. INFECTION WITH ECHINOCHASMA PERFOLIATUS This species was first described as Echinostomum perfoliatum by von Ratz in 1908111 after he had found it in the small intestine of cats and dogs i n Hungary. 47 mature worms were found in the gall bladder a t autopsy. but subsequent experience has shown that these drugs are not always reliable. the generic name being derived from the Greek words (ECHINOS) and µ (CHASMA) meaning "spine" and "hiatus". respectively. INFECTION WITH ECHINOPARYPHIUM RECURVATUM This cosmopolitan parasite of the intestine of birds and mammals wa s described by von Linstow in 1873 80. the excretion o f eggs in the stools is transient compared with patients with true dicrocoeliasis. Th e worm is a common parasite of cats and dogs in many parts of the world. Praziquantel may prove to be effective. the first was by Morishita.Miscellaneous Trematode Infections 299 Cobbold39. . are spurious. but was re-described as E. In 1911. Odhner transferred this helminth to the genus Echinostoma 99. miracidia penetrated the snails Gyraulus convexiusculus and Hippeutis umbilicus. metamorphosed into rediae. The parasite was named after the Lak e Lindoe region of Central Celebes where human infection was common. Tubangui and Pasco described the life cycle of the parasite (which they called Euparyphium ilocanum). the name was derived from a combination of the Greek words (ECHINOS) and µ (STOMA) meaning "spine" and "mouth". Phil ippines by Garrison in 1907. loaches were collected from the same restaurant in which two of the patients had eaten. the n produced daughter rediae and cercariae. the latter being liberated and encysting on freshwater molluscs which may be eaten raw 137. Recently. Since the prisoner came from the Ilocano region of the Philippines. Subsequently. in 1908 he named i t Fascioletta ilocanum 53. 2-6 mm long. Arizono and his colleagues descr ibed infections in four people who ate loaches (Misgurnus anguillicaudatus). with first Tubangui (1 931) showing that rats. prashadi was shown subsequently to be the primary intermediate host in India. The dog wa s necropsied after 33 days and five adult worms were recovered from its small intestine9. ILOCANUM Eggs of this fluke were first found in the faeces of prisoners in Manila. Egg s appeared in the faeces after two weeks and the volunteers developed abdominal pain lasting for several days about one month after infection. E. G. were reservoirs of infection. Worms attach to the intestinal wall and may cause diarrhoea. In 1933. with up . E. Indonesia 28. Radomyos and colleagues have shown that praziquantel is effective in the treatment of this infection 107. ilocanum by Brug and Tesch in 1937 in the Celebes (Sulawesi). parasites wer e recovered from the soft tissues adjacent to the gills and a puppy was fed with 40 metacercariae and two humans ingested 10 metacercariae each. LINDOENSE This species was first reported as E. respectively. It was placed in the genus Echinostoma of Rudolphi (1809) and emended by Dietz in 1910 45. after administration of oleoresin of aspidium to one person. lindoense by Sandground and Bonne in 1940 119. then Chen finding that dogs. The parasite was found subsequently in various parts o f southeast Asia.300 A History of Human Helminthology ECHINOSTOMIASIS E. In 1976 . HORTENSE This parasite was first described by Asada in 1926 11. He l ater recovered 21 adult worms. The first intermediate hosts a re a number of species of snails. and was named E. the worm has become less prevalent as a result of changes in the eating habits of the population32. described originally as Fasciola melis by Schrank in 1788 122. then renamed E. which is normally a parasite of t he intestine of various small animals and birds such as musk rats. Hsu57 found two worms in the intestines of a Chinese who had died of chroni c myeloid leukaemia and concluded that they were identical with the wor m . encyst in the tissues of tadpoles and frogs. E. It was recovered by Leon in 1916 from the stools of a Rumanian patient who had been in Jassy. MACRORCHIS AND E. Majima found 66 adult E.Miscellaneous Trematode Infections 301 to 96% of the inhabitants being infected. The parasite has also been found in Brazil wher e Biomphalaria glabrata is the vector 78. with mussels being important second intermediate hosts 24. hedgehogs and dogs. revolutum by Looss in 189983. convexiusculus. malayanum by Leiper in 1911 74. In recent years. Since then. E. geese and fowl. ducks. Leon and Ciurea named the worm Echinostoma jassyense in 192276. E. MALAYANUM This parasite was first found in two Tamil coolies in Singapore and Kual a Lumpur. macrorchis in the intestines of a boy in Japan in 1927 90. and the second intermediate hosts on which encystation occurs are molluscs an d tadpoles. Iran . is normally a parasite of badgers. The first infection found in humans was reported by Anazawa i n 1929. which were first described by Ando and Ozaki in 19238. INFECTION WITH EUPARYPHIUM MELIS This fluke. The molluscan intermediate host s were shown by Bonne to be Anisus sarasinorum and A. He also reported that diarrhoea was induced in experimental human infections. was first described by von Froelich in 1802 as Fasciola revoluta 52. REVOLUTUM This fluke. he recovered adult worms from the faeces of a Taiwanese woman who had been treated with oleoresin of aspidium 7. Species of Lymnaea and Indoplanorbis were shown to be the first intermediate host by Rao110 and then by Lie and Virik 79. occasional infections of humans by both species have been reported fro m various parts of southeast Asia 25. CINETORCHIS The metacercariae of these parasites. The worm is common in parts o f northeastern India where more than 40% of the population may be infected 29. 999 worms were recovered from one individual. which are approximately 1 cm long and almost as much wide. DISCOS) meaning "belly" and "disc". Pigs are a common reservoir host but various species of monkeys have also been found to be infected. Snails are the first intermediate host and cercariae encyst on tadpoles. these in turn developed into adul t worms in the pancreas of goats15. in which they grew to mature metacercariae. buffalo . goats and hares in Asia and other parts of the world. That parasite. but it is also found in other parts of Asia. but the snail. The life cycle of this parasite was determined in 1965 by Basch who fed sporocysts from a snail. had been transferred to th e genus Euparyphium. Mechanical t herapy with soap and water enemas . It wa s then transferred to the genus Eurytrema by Looss in 1907 84. respectively. to grasshoppers. Castellani and Chambers in 1919 recorded the presence of eggs of this tr ematode in the faeces of a Chinese coolie 33. among which was a Distoma pancreaticum from the pancreatic duct of a sheep. Humans may be infected with large numbers of thes e helminths. simply by the administration o f soap and water enemas29. Conocephalus maculatus . The generic name is derived from the Greek words (GASTER ) and (DISKOS. Parasites generally attach to the large bowel and the infection may cause diarrhoea. The life cycle is uncertain. Subseqently. it was called Gastrodiscus hominis by Sonsino (1896) 128. It was discovered in Japan and became first known to Europeans during the Paris Exhibition of 1889 when Janson from the A gricultural School of Komaba in Japan exhibited a series of parasites. The new parasite was referred to in subsequen t years by Railliet (1890) 109 and by Janson (1893) 58 in papers which dealt with the anatomy and pathological significance of the worm. has been infected experimentally 48. Adult worms were found in the pancreatic duct of a 22 year old Chinese man a t autopsy by Chang and Li in 1964 34 INFECTION WITH GASTRODISCOIDES HOMINIS This fluke was first found in the caecum of an Indian patient and designate d Amphistomum hominis by Lewis and McConnell in 187677.302 A History of Human Helminthology described by Schrank. then was redescribed i n 1913 by Leiper who renamed it Gastrodiscoides hominis 75. sheep. meanwhile. with the suffix (EIDOS) indicating "like" or "similar". INFECTION WITH EURYTREMA PANCREATICUM This fluke is a common parasite of the pancreatic ducts of cattle. respectively. respectively. Bradybaena similaris. Helicorbis coenosus. The generic name is possibly derived from a combination of the Greek words (EURYS) and µ (TREMA) meaning "broad" and "hole". The generic name is derived from a combination of the Gree k words (HAPLOOS) and (ORCHIS) meaning "single" an d "testis". In 1900. but little more was heard of thi s 81 fluke until Blanchard in 1891 21 then Looss in 1894 once again directed attention to its presence in Egypt. von Sie bold published Bilharz's letter and added his own comments in which he named the parasite Distoma heterophyes 20. in the intestine of a boy' s cadaver a large number of small red dots which. pumilio. described by Nishigori in 1924. nocens 101. The worm s were seen on another occasion by Bilharz. tachui infections have also been reported in Thailand67. INFECTION WITH HAPLORCHIS SPECIES H. This was criticized by Lane in 1922 who noted that all the observed changes could be accounted for by muscula r . In 1915. described by Katsuta in 1932. yokogawai. Their paper was published in Japanese but Cor t and Yokogawa brought it to the attention of the English-speaking world in 1921 42. In 1866. HETEROPHYES This fluke was discovered in 1851 in Cairo by Theodor Bilharz. respectively. described by Looss in 1896 82. according to the nomenclatural law of priority. They called this worm H. tachui. and H. He wrote to von Siebold in Breslau in Germany (now Wroclaw.3 mm in width. 20 In the following year. to reflect both the specific name given to it by von Siebold as well as the land of its discovery 40. under the microscop e proved to be beautiful fully developed Distoma 1 mm in length and 0. Th e efficacy of praziquantel needs to be evaluated. H. The red color was due to the red-brown mature eggs which were visible through the body of the worm. as is treatment with thymol or tetrachlorethylene. The distinction between the two species was based upon small differences in size. heterophyes but which they believed represented a different species.Miscellaneous Trematode Infections 303 is often successful. respectively. Cobbold placed the worm in a distinct genus and named it Heterophyes aegyptiaca. Poland) on 1 May 185 1 recounting his discovery: A short while ago.3. heterophyes 131. H. have all been reported in humans in the Philippines2. Stiles and Hassal renamed it . Onji and Nishio in Japan de scribed a fluke found in human intestine which resembled H. on 26 April. INFECTION WITH HETEROPHYES SPECIES H. The specific name was derived from a combination of the Gree k words (HETEROS) and (PHYE) meaning "different" and "shape". H. I discovered. Kobayashi purchased some Egyptian mullet in Port Said and found in them metacercariae resembling youn g Heterophyes 69. sometimes associa ted with bleeding from the gastrointestinal tract 65. Subsequently. The infection was t ransmitted experimentally from the fish. Adult worms and eggs were both seen when faeces we re being examined microscopically for schistosome ova120. Asada completed the life cycle of Heterophyes by obtaining adult worms after feeding fish. a view which has become accepted generally. which had been infected in this way. heterophyes were obtained 65. The parasites were recovered from humans treate d with thymol. heterophyes. however. The second intermediate host of H. H. H. nocens was a synonym of H. dogs and foxes. adult worms have been found in the brain 43. While returning to Japan after a visit to Europe. Mugil cephalus. and that when they were fed to a dog. . That these were indeed Heterophyes was proven by Khalil who fed encysted cercariae in Mugil cephalus. for example. Mugil cephalus (mullet). The parasites occasionally lodge in ect opic locations. Khalil in Egypt showed in 1933 t hat cercariae from the snail. from Lake Menzaleh near Port Said. Thi s was then soon confirmed for H. Gambusia affinis. Filix mas and tetrachlorethylene have been used in the past for the treatment of this condition. adult H. He found subsequently that Tilapia nilotica was also infected65. Asada in Japan discovered that a brackish-water snail . to dogs 12. heterophyes.304 A History of Human Helminthology contraction 73. heterophyes in Egypt by Harujiro Kobayashi and Mohammed Khalil. the parasite may produce diarrhoea. Heterophyiasis was diagnosed in life for the first time in 1899 in a girl who was a patient of FM Sandwith in Kasr-el-Aini Hospital in Cairo. heterophyes infection has since been found in other mammals includin g cats. In 1928. heterophyes was identified before the first intermediate host. Nevertheless. Onji and Nishio sh owed in 1915 by feeding experiments that cercariae of Heterophyes encysted in the fish. Pirenella conica. Tympanotonus microptera (= Cerithidea cingulata) was the first intermediate host of Heterophyes. until the appearance of Cort and Yokogawa's translation of Onji and Nishio's work in 1921. working independently. Sandwith also noted that she had no particular symptoms that could be attributed to the infec tion. was described by Ozaki an d Asada in Japan in 1925. In addition to humans. He showed that cercariae from these snails encysted i n saltwater fishes but did not complete their development in freshwater fishes . would encyst in the muscles of the fish. KATSURADAI This fluke. this observation was not generally appreciated. closely related to H. and other investigators showed that Aphanius in Egypt and Acantogobius in Japan were other second intermediate hosts. to cats then recovered adul t worms eight days later64. to a dog102. Lane concluded that H. but who may have acquired the infection after eating raw clams i n New York. yokogawai was discovered before the molluscan first intermediate host. is a common parasite of birds such as ducks. The infection has been described in humans only once. then Ciurea in 1915 designated it Loossia. Metagonimus.5 mm long. In 1911 in Taiwan. Yokogawa's discovery was reported to the Japanes e Pathological Association by Katsurada at which time he gave the fluke th e name Heterophyes yokogawai. S. but the designation for the species was pre-empted by Katsurada. and renamed by Dietz in 1909 44. thus naming it Metagonimus yokogawai 61. INFECTION WITH HYPODERAEUM CONOIDEA This fluke. Unaware of these publications in Japanese. Mühlens. at which time he named it Loxotrema ovatum 68. first recognized in 1782 by Bloch who named it Distoma conoideum 23. this was duly published on 31 May 1912 60. Metagonimus. The intermediate hosts are Planorbis and Lymnaea snails. Marine snails are the first intermediate host and metacercaria e encyst on bivalves such as Mytilus and Mya. In 1912. was first found by H Kobayashi in 1908. was used for the first time in the non-Japanese literature by Yokogawa in Decembe r 1913150. Yokogawa had found this parasite in humans and in cats and dogs infected experimentally with cysts from the trout . described by Vogel in 1933 and named by him after it s discoverer. in which to place the worm. respectively. Not only was the name Loxotrema preoccupied by a genus of the Mollusca. Leiper. The infection is common in some parts of Thailand. is derived from a combination of the Greek words µ (META) and µ (GONIMOS) meaning "posterior" and "genitalia". Metagonimus yokogawai . The piscine second intermediate host of M. Metagonimus yokogawai . erected the genus Yokogawa for this parasite 75. Mühlen s obtained five specimens from a German patient who had lived in Colombia for six years. a fluke about 1-2. The generic name. later i n 1913. geese and fowl. In the following month (30 June 1912). is a para site of gulls and other birds 140.Miscellaneous Trematode Infections INFECTION WITH HIMASTHLA MUEHLENSI 305 This fluke. The correct name. but he did not publish his report of the discovery until 10 October 1912. where more tha n half of the population may be infected 148. The generic name (HIMASTHLE) meaning "thong" or is derived from the Greek word µ "strap". Katsurada erected a new genus . Yokogawa reported tha t . Plectoglossis altivelis. METAGONIMIASIS The causative agent of this infection. Further studie s . R im showed that niclosamide was often effective112. with the result that eggs of M. He found that miracidia developed through a sporocyst stage then two generations of rediae. Subsequent investigations revealed tha t Odontobutis obscurus and Salmo perryi were also vectors of infection. Muto demonstrated that Melania (= Semisulcospira) libertina was the first intermediate host. other investigators found that many species of fish-eating mammals wer e reservoirs of infection. Yokogawa had discovered in 1911 that dogs could be infected experimentally with this parasite. Muto took cercariae from the liver of infected snails and showed that direct infection of experimenta l definitive hosts could not be induced. Subsequently. Askanazy then discovered the worm in five people living in the East Prussian district of Heydekrug. respectively.150. In 1895. Praziquantel may well prove to be a valuable addition to the therapeutic armamentarium. He found the parasite i n nine patients and named it Distomum sibiricum 143. Yokogawa in 1913 indicated that thymol was effective in the treatment of metagonimiasis 150. Plectoglossis altivelis. yokogawai appeared in the faeces 1 2 days later95. The generic name was derived from a combination of th e Greek words (OPISTHON) and (ORCHIS) meaning "posterior" and "testis". was discovered in the biliary passages of a cat by Rivolta in 1884 and named Distomum felineum by him113. the worm thus being known as O. in the Siberian region of the USSR. the specific designation reflecting the host in which it was found.96. Winogradoff first reported this infection in humans. Kobayashi in 1912 68 reported that dogs in Japan were infected with Metagonimus. Tetrachlorethylene has also been used. He then exposed goldfish and carp to the cercariae and proved that they penetrated the skin of the fish and becam e infective after about 20 days. As mentioned earlier. and that eggs appeared in the faeces within one week of the parasites being fed to experimental animals149. while more recently. In 1917. Several years earlier (1892) in Tomsk. The encysted metacercariae in fish were then fed to cats. OPISTHORCHIASIS OPISTHORCHIS FELINEUS This fluke. about 1 cm long. Kholokowsky diagnosed the infection in a peasant from near Leningrad but who had travelled extensively in Siberia 66. Subsequently.306 A History of Human Helminthology encysted cercariae occurred in the freshwater trout. then Leiper and Atkinso n found that natural infections were common in dogs in Shanghai. R Blanchard erected the genus Opisthorchis and placed this fluke in it. Clinical studies have indicated that infection occasionally produces diarrhoea particularly if the infection is heavy 123. felineus 22. then penetrated into the tissues. Ciurea stated that he believed that Askanazy had been in error and had probably been working with holostomes 38. pigs. rutilus could be the metacercarial stage and that an earlier phase perhaps passes in the body of a small bivalve mollusc. Vogel observed that when cercariae enco untered the fish. and suggested that an encysted larval worm found in Prussia in the flesh o f L. Vogel also investigated the route of migration of the worms in the definitive host. but unlike Fasciola. viverrini infections and is presumably also active against O. Barbus. The diagnosis is made by finding eggs in the faeces or duodenal fluid. leachi is the only species of snail which has been shown to be susceptible to infection with this parasite . then recovered mature O. Patients with 50 or so worms usually had no ill-effects. felineus was elucidated in fits and starts.Miscellaneous Trematode Infections 307 revealed that a wide range of mammals including dogs. foxes. but people with many hundreds of worm s sometimes had severe biliary and hepatic disease. Worms in the bile passages may induce inflammation and subsequent fibrosis leading to biliary obstruction and secondary bacterial infection an d cholelithiasis. idus and L. Cyprinus. metamorphosed into first then second generation sporocysts. then migrated through the ampulla o f Vater to the distal bile passages wh ere they became attached to the mucosa and matured. Abramis. In 1917. Clinical studies indicated that the likelihood of significan t damage depended upon the number of worms present. felineus. metacercariae of O. The life cycle of O. . they became attached to the scales. were also hosts of the larval stage of O. Subsequent studies by a number of investigators demonstrated that other freshwater fishes of the genera. Ciurea isolated encyste d cercariae from the fishes Tinca tinca and Idus idus. Dreissena polymorpha 86 . rabbits and seals were infected in cent ral and eastern Europe and adjacent parts of the USSR 49. Blicca. Praziquantel has been shown to be effective in the treatment of O. and Scardinius. Askanazy i n 1905 believed that he had shown that the fishes Idus melanotus (chub) and Leuciscus rutilus (roach) were the intermediate hosts 14. then the miracidia mig rated into the tisssues. then produced rediae in which th e cercariae developed after about two months. beginning the laying of e ggs about three to four weeks after ingestion. felineus twelve days after feeding the parasites to cats and dogs. dropped their tails. He showed that like Clonorchis. rats. cats. Hexachloroparaxylol (chloxyl) was claimed to be partially effective in Russia n patients with opisthorchiasis103. He found that eggs hatched after they were ingested by the snails. The nature of the first intermediate host of the fluke remained obscure until 1934 when Vogel showed that development of the parasite occurred in th e snail. Bithynia leachi 141. B. felineus excysted in the duodenum. felineus. Lühe then indicated that the details of the development of the parasite were known only meagrely. Partial responsiveness t o dehydroemetine was shown by Muangmanee and co-investigators in 1974 94. NOVERCA . abdomina l pain and jaundice in patients with opisthorchiasis. felineus 63. Upatham and col leagues have shown more recently in a study of a village with 309 inhabitants that right upper quadrant abdominal pain was more common in those persons with heavy infections 138. On the other hand. Differentiation between the two species is extremely difficult. A number of drugs have been proposed as a treatment for opisthorchiasis viverrini. although Leiper (1911) made a provisional diagnosis of O. while the most important fis h intermediate hosts were species of Cyclocheilichthys. with up to half of the population being infected in some areas 54. it is possible that the correct name for this parasite is O.106. and could find no significant dif ferences between the two groups 145. Bunnag and Harinasuta showed in 1980 that the infection responded well t o praziquantel.308 O. The life cycle of this parasite was studied in Thailand by Wykoff and hi s colleagues. Wykoff and colleagues in 1965 could not distinguis h between them on the basis of the appearances o f the adult worms or of the eggs. laevis. they showed that the snail intermediate hosts were Bithynia goniomphalus.117. Niclofolan was thought to be of some value in patients with light infections 6. Most early reports of this infection in southeast Asia referred to this parasite as O. Early clinical studies suggested a high frequency of diarrhoea. Wykoff and co-workers compared th e clinical and biochemical findings in 921 infec ted persons with those in a similar number of uninfected persons in Thailand. reflecting the Distoma tenuicollis described by Rudophi in 1819 116. for example. tenuicollis. The diagnosis is usually made by findi ng eggs in the faeces. O. 23 out of 26 patients were cured by a two day course of treatment and toxicity was minimal 30. Hampala and Punteus 146. but these studies were not well-controlled 54. It was transferred to the genus Opisth131 orchis of Blanchard 22 by Stiles and Hassal in 1896 . Kerr 74. Upatham and his collaborators have defined recently the relationship between intensity o f infection and faecal egg excretion138. Nevertheless. funiculata and B. but found differences in the patterns of the flame cells in the cercariae 146. The infection is now recognized as being common in Thailand. Subsequently. It is possible that there is an association betwee n opisthorchiasis and carcinoma of the bile duct. B. VIVERRINI A History of Human Helminthology This fluke was first found in a civet cat (Felis viverrus) by Poirier in 1886 and named Distoma viverrini by him104. 5896 worms were found an autopsy of a man who died from this neoplasm 54. viverrini for some flukes from two prisoners in Chiengmai gaol in Thailand that had been sent to him by Dr. The species of Plagiorchis normally occur in the . Th e first patient was a Muslim who died in Calcutta in 1876. The generic name is derived from the Greek words (PHILO-) and µ (OPHTHALMOS) meaning "like" and "eye" . According to Artigas and Perez 10. i t was named O. It has been recorded twice i n humans. post-morte m examination revealed small flukes in dilated intrahepatic bile ducts 87. respectively. Gomez and Montalvan in Ecuador in 1949 found this parasite in a number of humans and dogs114.Miscellaneous Trematode Infections 309 This fluke. The details of the life cycle are uncertain. O. McConnell. The generic name is derived from the Greek word s (PARAPHYE) and µ (STOMA) meaning "fringe" and "mouth". which is a common parasite of dogs and pigs in India. India and named Artyfechinostomum sufrartyfex by Lane in 1915 72. It is derived from the (PLAGIA) and (ORCHIS) meaning "oblique" and Greek words "testis". this worm is identical with Amphimerus pseudofelineus described in cats by Ward in 1901. which is probably a synonym of P. but A. respectively. Indoplanorbis exustus 108 . Parasites of this genus develop in a snail intermediate host and do not require a second intermediate host 4. INFECTION WITH PHILOPHTHALMUS Worms of the genus Philophthalmus mainly parasitize the conjunctival sac of the eyes of birds. sufrartyfex. on both occasions by McConnell in India. It is also possible that this species is synonymous with Echinostoma malayanum described by Leiper in 1911. utilizes the snail. like Lewis and Cunningham. noverca by Braun in 1902 26. GUAYAQUILENSIS Rodriguez. PLAGIORCHIASIS The genus Plagiorchis was raised by Lühe in 1899 85. INFECTION WITH PARYPHOSTOMUM SUFRARTYFEX This worm was first obtained from an eight year old girl in Assam. considered it to be identical with Distoma conjunctum discovered by TS Cobbold in the liver of an American red fox in 1858. It was later redescribed and transferred to the genus Paryphostomum of Dietz (1909) by Bhalerao in 193119. McConnell encountered another patient i n 1878 and on this occasion noted that the flukes were somewhat larger than those described by Cobbold 88. mehrai. was firs t found in these animals in that country by Lewis and Cunningham in 1872. respectively. Human ocular infection was firs t described by Markovic in Belgrade in 1939 91. P. P. PHILIPPINENSIS Africa and Garcia first found this fluke in 1935 during the autopsy of a man from Ilocano. The generic name is derived from a combination of the Gree k words (PYGIDION) and (OPSIS) meaning "posterior" o r "rump" and "sight". concurrent infection with Metagonimus yokogawai 13.134. respectively. McMullen in 1937 infected himself experimentally89. It has been reported in humans in Korea124. This genus is closely related to. INFECTION WITH PYGIDIOPSIS SUMMA Onji and Nishio described this fluke in 1915 101. but they left it un-named 1. A natural infection in a human has been reported only once. The generic name is derived from (POIKILOS) and a combination of the Greek words (ORCHIS) meaning "many" or "various" and "testis". Snails are the intermediate host s although aquatic mussels may also serve as second intermediate hosts. MURIS Tanabe described this fluke in 1922 133. People in this region o f the Philippines were in the habit of eating grubs of certain species of insect s which may be the second intermediate hosts. respectively. . P. INFECTION WITH POIKILORCHIS CONGOLENSIS This fluke was described by Fain and Vandepitte in 1957 after they had found it in a retroauricular cyst removed from a boy in Central Africa 50. Achillurbania 16. Eggs similar to those produced by this parasite had been removed previously from near the ear of a man by Yarwood and Elmes in 1943 147. it was given its curren t name by Sandground in 1940 118. it was found in a Japanese patient who was being treated for a heavy .310 A History of Human Helminthology intestines of a wide range of vertebrates. JAVENSIS Sandground in 1940 first found this worm in a Javanese who also had a heavy infection with Echinostoma ilocanum 118. Philippines. That first patient was also infected wit h Echinostoma ilocanum and Spelotrema brevicaeca . or may be identical with. salmincola of Chapin. but encysted metacercariae have been found in the crab . has been reported in humans in Japan. the parasite thus being designated T. Oxytrema silicula. Taiwan and Hawaii 5. It was then renamed Nanophyetus by him in the following year 36. In the following year. The free-living cercariae encyst in the kidneys of certain species of fish. eggs have been observed in the centra l nervous system 2 and in the heart 3. In lower animals. was described in 1926 by Chapin who named it Nanophyes salmincola 35. In humans. febrile illness In 1931. The complete life cycle is unknown. of Odhner 100. respectively. Praziquantel may be more active. It was renamed Spelotrema brevicaeca by Tubangui and Africa in 1938 136. Carcinus maenas 56. Troglotrema. Bennington and Pratt showed in 1960 that the mollusc. which lives in the intestinal wall of a number of carnivorou s animals on the northern borders of the Pacific ocean. . Thymol was found to be effective in the original patients described b y Skrjabin and Podjapolskaja 127. the worm is a vector of a rickettsia which often produces a fatal. The generic name is derived from the Greek words (TROGLE) and µ (TREMA) meaning "sunken" and "orifice". and transferred the parasite to the genus. then Conyngham named it Amphistomum watsoni in 190441.59.Miscellaneous Trematode Infections INFECTION WITH SPELOTREMA BREVICAECA 311 This fluke was first reported a s Heterophyes brevicaeca in 1935 by Africa and Garcia who found it in the intestine of a Filipino male 1. described by Onji and Nishio in 1915 101. INFECTION WITH STELLANTCHASMUS FALCATUS This fluke. INFECTION WITH TROGLOTREMA SALMINCOLA This worm. is the first intermediate host 18. INFECTION WITH WATSONIUS WATSONI This parasite was discovered in the intestine of a Nigerian by Watson and sent to Conyngham in London. Witenberg concluded that this fluke was identical with the N. The parasite was renamed Watsonius watsoni by Stiles and Goldberger in 1910 129. salmincola 144. however . particularly salmon and trout. Skrjabin and Podjapolskaja found that a number of men inhabiting the Amur and Usuri regions of the US SR were infected with a fluke which they named Nanophyetus schikhobalowi 127. The flukes were pronounced a new species b y Blanchard. Journal of the American Medical Association 110: 1100-1101. AMBROISE-THOMAS P. Considerações sôbre Opisthorchis pricei Foster. 1931 20. 1939. Th. Abstracted in Japan Medical World 8: 134.) Taiwan Igakkai Zasshi No. À propos de 51 cas. 1937. pp 221-224. In Japanese. In Japanese 9. in Japan. Gomez et Montalvan. Schriften der physikalisch-oekonomischen Gesellschaft zu Königsberg 46: 127-131. OKAHASHI K. Tokyo Iji Shinshi No. guayaquilensis Rodriguez. 1938 6. Two more cases of hear t failure associated with the presence of eggs in sclerosed valves. BASCH PF. wit h English summary 10. BEAVER PC.. Bilharz in Cairo. OTAGAKI H. SAKAI Y.) Japanese Journal of Parasitology 25: 36-45. 1923. 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Annotationes Zoologicae Japonenses 12: 143-173. KRULL WH. 94. Transactions of the Royal Society of Tropical Medicine and Hygiene 6: 265-297. 1922 LEIPER RT. pp 217. Journal of Tropical Medicine and Hygiene 66: 77-82. 1940 (Trematoda: Echinostomatidae) with a report of its occurrence in Brazil. I. V. 77. 83. Artyfechinostomum sufrartyfex. Journal of Parasitology 23: 113-115. 73. Lancet i: 343-344. 1931 MUANGMANEE L. Observations on certain helminths of man. 95. Proceedings of the Asiatic Society 8: 182-186. Abstracted in Japan Medical World 8: 70. 86. Zur Kenntnis einiger Distomen. Formica fusca. 1899 LOOSS A. Cionella lubrica (Müller). 1968 LIE KJ. Un nouvel échinostome che l'homme. Abteilung für Systematik. 80. Amphistoma hominis. 82.Miscellaneous Trematode Infections 315 71. 1873 LOOSS A. Some avian trematodes from Japan especially Formosa.sp. Archiv fü r MARKOVI Ophthalmologie (von Graefe) 140: 515-526. Recherches sur la faune parasitaire de l'Egypte. 88. 84. with a reference list af all known Japanese species.) Kyoto Igaku Zasshi 14: 79-100. 90. Oekologie und Geographie der Tiere. 81. In Japanese. IX. Sur un cas de dicrocoeliose chez l'homme. metacercaria. Zoologischer Jahrbucher. A note on Heterophyes nocens as a distinct species of trematode parasite. An experimental infection with Plagiorchis muris in man. with German summary. 1878 McMULLEN DB. 1929 MTSCHEDLIDZÉ J. Parasitische Plattwürmer. Ueber den Bau von Distomum heterophyes von Sieb. Mémoire s Présentés à l'Institut d'Égypt 3: 1-252. 1899 LÜHE MF. Liverpool. 1876 LIE KJ. Notes on the cyst. 1917. Zoologische Anzeiger 22: 524-539. und Distomum fraternum n. 1913 LEON N. 78. Studies on the biology of Dicrocoelium dendriticum (Rudolphi 1819) Looss. MAPES CR. 91. 1928 A. n. "Distoma conjunctum". Annales de Parasitologie Humaine et Comparée 9: 68-71. Heft 17. JAROONVESAMA N. 75. 1952. Einige neue Distomen und Bemerkungen über die weibliche n Sexualorgane der Trematoden. Lancet i: 476. Cornell Veterinarian 42: 339-351. Première partie. pp 54-56 . Annals of Tropical Medicine and Parasitology 1: 128-134. McCONNELL JF. 1974 MUTO M. 1953 LANE C. 1963 von LINSTOW OF. 1911 LEIPER RT. 87. 1939 MORISHITA K. 74. 2552. In Japanese. and infection in the ant . On the "Distoma conjunctum" as a human entozoon. sp. In Russian 106. ODHNER T. KALINTINA ZI.) Tokyo Iji Shinshi No. sp. sp. Report of a case of Opisthorchis felineus in Siam. A note on dicrocoeliasis andFasciola gigantica infection in livestock in northern Ghana with a record of spurious and of genuine Dicrocoelium hospes infections in man. 1908 112. SANDGROUND JH. (The development of Dicrocoelium dendriticum on high altitude grounds of central Caucasus. 1922. Studies on the chemotherapy of trematode infections in Korea. Berolini. In Russian. pp 7-8 97. Bulletin de la Société Philomathique. In Japanese. FIRSOVA RA. RADOMYOS P. 79. Artyfechinostoma mehrai infestation. (Effectiveness and OV tolerance of the 3-day scheme of chloxyl treatment of opisthorchiasis. Echinostoma ilocanum (Garr) ein neuer Menschen Parasit aus Ostasien . RUDOLPHI CA. ASADA J. Les parasites des animaux domestiques au Japan. Abstracted in Japan Medical World 6: 42. 143. NISHIO K. In. 1949 115. 1915.Echinostoma ilocanum (Garrison. Studies on Opisthorchis viverrini in Thailand. 1973. Echinostoma lindoense n. Bacteriología. American Journal of Hygiene 62: 81115. Sumtibus Augusti Rücker. POIRIER MJ. 1886 105. Sopra una specie di Distoma nel gatto e nel cane. infection in man in Thailand. Die Verwaudschaftsbeziehungen der TrematodengattungParagonimus Brn. von RATZ I. Revista de Medicina Tropical y Parasitología. with an accountof its life history and epidemiology. POPOV KK. SRINIVASAN T. KARNAUKH VK et al. Journal of the Indian Medical Association 38: 485-487. 1962 109. with German summary. BUNNAG D. Revista Ecuatoriana de Higiene y Medicina Tropical 6: 11-24. RAILLIET A. Journal of Parasitology 12: 216-218. 1819 117. Zoologischer Anzeiger 38: 65-68. SADUN EH. Kyoto Igaku Zasshi 14: 115-134. Heterophyes katsuradai n.) Meditsinskay a Parazitologiya i Parazitarn e Bolezni 42: 581-585. Annals of Tropical Medicine and Parasitology 21: 9-10. Southeast Asian Journal of Tropical Medicine and Public Health 13: 265-269. Húsovökben élö trematodák. Giornale di Anatomia. Plagiorchis javensis n. 1917. Annals of Tropical Medicine and Parasitology 61: 215-218. series 10. 1908) Odhner 1911. 1884 114. RIVOLTA S. RAGHUNATHAN VS. Fisiologia e Patologia degli Animali 16: 20-28. Habana 6: 207-211. A preliminary report on the adult trematode obtained from Cercaria indicae Sewell. RIM HJ. Uppsala 3: 231-246. a new trematode parasite of man in the Celebes. (Ueber der ersten Zwischenwirt des Metagonimus yokogawai). MUTO M. 1911 100. Zoologiska Bidrag Frân. 1962. Entozoorum synopsis cui accedunt mantissima duplex et indice s locupletissima. RUDOLPHI CA. (On a new species of Katsurada's Heterophyes family of parasites found in a human case. 1982 108. 1925. 1803 116.) Zoolohichn Zhurnal Ukrayin 41: 1793-1797. GOMEZ LF. (General observations on new intestinal flukes. MONTALVAN CJ. Korean Medica l Journal 12: 425-457. PROMMAS C.) Igaku Chuo Zasshi 14: 875-883. ODHNER T.. HARINASUTA T. Neue Beobachtungen über die Eingeweidewürmer. ODEI MA. 1940 119. Trematodes nouvelles ou peu connus. 1966 99. sp. 1940 . OZERETSKOVSKAYA NN. 1914 101. In Japanese. RODRIGUEZ JD. 1975 113. with English summary. Le Naturaliste No. Also: A new human trematode. 1890 110. Fleischfressern lebende Trematoden . 1955 118. El Opisthorchis guayaquilensis (una nueva especie de Opisthorchis encontrada en el Ecuador). American Journal of Tropical Medicine 20: 511-535. 2445. Indian Journal of Veterinary S cience and Animal Husbandry 3: 317-320. ONJI Y. 1922 111. RAO MA. A new trematode parasitic in man. Befunde bei Schnecken von Thüringer Schwafweiden in eine m Lanzettegelgebeite. OZAKI Y. In Japanese 102. 1929 98. Kulonleyamat az Allatani Kozlemenyek 7: 15-20. 1927 107. 1926. 1926 103. 104.316 A History of Human Helminthology 96. BONNE C. NÖLLER W. Tierärtzliche Rundschau 35: 485-489. Archiv für Zoologie und Zootomie 3: 1-32. SANDGROUND JH. pp 811. 7: 27-29. 1938. 1934 142. 791. (Echinostoma paraulum . 1894. Sobre um interessante trematodeo parasito dos seios maxilares de gamba (Didelphis marsupialis). BRO CKELMAN. Lancet ii: 888. pp 560-611. 1929 140.S. 387. VAJRAST HIRA S. with type of D. 1896 129. Abstracted in Tropical Diseases Bulletin 29: 48. UPATHAM ES. Morbidity in relation to intensity of infection in opisthorchiasis viverrini: study of a community in Khon Kaen. SKRJABIN KI. MENDHEIM H. 1981 125. On the Japanese Echinochasmus perfoliatus. Revista Brasileira Biologia 2: 213-218. SCHOULZ GS. 1782 123. SEO BS. Zeitschrit für Tropenmedizin un d Parasitologie 2: 142150. Studies on intestinal trematodes in Korea. SCRIABINE KI (=SKRJABIN). The systematic position of some trematodes reported from the Philippines. 1931 128.A. VIYANANT V. SKRJABIN KI.) "Tropical Medicine and Veterinar y Science" 8: 16-25.. Annual Report of the Bureau of Animal Industry. 1933 141.Miscellaneous Trematode Infections 317 120. In Russian. Lepoderma muris n. 1922. sp. Parasitenkunde und Infektionskrankheiten. AMENDA R. STROM J.und Tropen-Hygiene 33: 474-489. TRAVASSOS L. VOGEL H. Archiv für Schiffs.S. 1922. HASSALL A. U. 1973 126. 1927. SAOWAKONTHA S.) Meditsinskay a Parazitologiya i Parazitarn e Bolezni 7: 129-138. 1950 122. FALÇÃO J. III. Intraretinal larval trematode. 1932 124. Himasthla muehlensi n. 1900 132. TANABE H. 1910 130. VOGEL H.g. Philippine Journal of Science 67: 117-127. Beobachtungen über Cercaria vitrina und deren Beziehung zum Lanzettegelproblem. Natura l human infections of Pygidiopsis summa and Heterophyes heterophyes nocens. Zentralblatt fürBakteriologie. Thailand. PASCO A. The life history of the human intestinal fluke. PODYAPOLSKAYA WP. Comparison of the type of Distomum longissimum von Linstow. 1896 131.) nebst Bemerkungen über Systematik und Epidemiologie. Nanophyetus schikhobalowi n. AFRICA CM. (Human and animal metagonimiasis in the Far East of USSR. VOGEL H. Abteilung originale 127: 385-391. On a new species of trematode. TANABE H. Philippine Journal of Science 51: 581-603. 1930. In Russian. sp. Contributo alla entozoologia d'Egitto. 1922 135. pp 47-58. SCHEID G. CHAI JY. Ein neuer Trematode aus dem Darm des Menschen. 1908). 60. Seoul Medical Journal 22: 228-235.) Okayama Igakkai Zasshi No. WALTERS J.) "Revue de Microbiologie e t Epidemiologie" 6: 433-437. TUBANGUI MA. The lung fluke (Paragonimus westermani) in swine and its relation to parasitic haemoptysis in man. Zoologica 33: 1-103. PODJAPOLSKAJA WP. Transactions of the Academy of Ophthalmology and Otolaryngology 770P: 784. longissimum corvinum Stiles and Hassal. Zentralblatt für Bakteriologie. Dicrocoelium . Zoologische Beobachtungen. MENARUCHI A. KURATHONG S. Study of the anatomy ofWatsonius (n. STILES CW. WARREN KS.. with French summary 127. Veterinary Magazine 3: 151155.nouveau parasite de l'homme. with English summary pp 476-477. SONSINO P. GOLDBERGER. 1982 139. In Japanese 134. HASSALL A. WY. Der Naturforscher. (On false distomiasis in the liver of man. sp. Abteilung originale 119: 294-297. SANDWITH FM. SHEA M. 1883. FREEMAN RS. (Contributions to the knowledge of the developmental cycle of digenetic trematodes.) watsoni of man and of nineteen allied species of mammalian trematode worms of the superfamily Paramphistomoidea. Die Lanzettegelinfektion (Dicrocoeliasis) beim Menschen nebst Mitteilung eines neuen Falles. FALLIS AM. In Japanese. Mémoires Présentés à l'Institut d'Égypte 3: 285-336. Der Entwicklungszyklus von Opisthorchis felineus (Riv. American Journal of Tropical Medicine and Hygiene 31: 1156-1163. Ratz). Department of Agriculture. 133. (Studies on the trematodes that use the fresh water fishas their intermediate hosts. 1938 137. ein neuer menschlicher Trematode der famili e Echinostomatidae. MABERLY AL. 1899 121. STILES CW. INTARAKHAO C. SCHRANK FP. STILES CW. HONG ST. 385. A case of Distoma heterophyes in a living patient. U. Abstracted in Japan Medical World 2: 270. Treasury Department. Hygienic Laboratory Bulletin No. II. Parasitologie und Infektionskrankheiten. Ueber den Lebenzyklus des Lanzettegels. Okayama Igakkwai Zasshi No. Halle 18: 66-85. VOGEL H. 1942 136. TUBANGUI MA. In Russian.Euparyphium ilocanum (Garrison. 1933 138. 148. 1912. 150. Paragonimus cyst in a West African native. 145. Hypoderaeum conoideum (Bloch 1782) Dietz 1909. 1913 143. In Japanese YOKOGAWA S. On the anatomy and systematic position of the causative agent of th e so-called salmon poisoning. Japanese Journal of Parasitology 14: 148-153. Transactions of the Royal Society of Tropical Medicine and Hygiene 36: 347-351. 1932 WYKOFF DE.) Izvestia Imperatorskogo Tomskogo Universiteta 4: 116-130. a common intestinal fluke of man in northeast Thailand. der die Forellenart iten Plecoglossus altivelis 1(Temminck) zum Zwischenwirt hat. 1965 YARWOOD GR. (A new parasite involvi g trout as its intermediate host and its new generic n name. JUTTIJUDATA P. HARINASUTA C. 1892 WITENBERG C. (On a new species of distomum [ istomum D sibiricum] in the human liver. 1892. CHITTAKYASOTHORN K. WINN MM. CHAROENLARP P. Clinical manifestations o f Opisthorchis viverrini infections in Thailand. 146. bildung einer neuer Gattung. WINN MM. Centralblatt für Bakteriologie. American Journal of Tropical Medicine and Hygiene 15: 915-918. 1966 WYKOFF DE. . Parasitenkunde und Infektionskrankheiten. 147. HARINASUTA C. 144. Journal of Parasitology 13: 258-263. Ueber einen neuen Paras Metagonimus yokogawai.the life cycle and comparison with O.318 A History of Human Helminthology dendriticum in Deutschland. Abteilun g originale 72: 158-179. 149. Opisthorchis viverrini in Thailand . Journal of Parasitology 51: 207-214. felineus. 1965 YOKOGAWA S. 1943 YOKOGAWA M. ELMES BG. 1954 WINOGRADOFF K (=VINOGRADOV).) Okayama Igakkai Zasshi No. 279. Abstracted in Centralblatt Allgemeine für Pathologie und pathologische Anatomie 3: 910-911. In Russian. Zeitschrift für Tropenmedizin und Parasitologie 5: 275-296. he wrote: "When the liver is filled with water and bursts into the epiploon. sheep and pigs. particularly in sheep. Mention is made in the Talmud of cystic lesions in the viscera of sacrificia l animals. depending upon the location of the cyst Diagnosis: suggested by radiology plus immunological studies. in his aphorisms on human medicine. cattle. In the tissues.Chapter 12 Echinococcus granulosus and ECHINOCOCCOSIS or HYDATID DISEASE SYNOPSIS Common name: hydatid Major synonym: Taenia echinococcus Distribution: world-wide. nucleated. in this case the belly is filled with water and the patient dies"(VII. Galen (129-c. live in the small intestinal lumen attach ed to the mucosa. each egg hatches a larva (oncosphere) which migrates through the bowel wall then passes via the portal venous system to the liver where many are arrested.55) 57. encysts and the wall differentiates into an outer. Similarly. In his commentary on the works of Hippocrates. Hippocrates (460-37 9 BC) alluded to tumours filled with water in the lungs of cattle. The whole cyst is surrounded by a fibrous layer of host origin. these in turn develop protoscolices on their inner surface. but the parasitic nature of these "bladders" was long unrecognized . When a cyst is ingested by a dog. Some larvae continue their migration to the lungs where they may either lodge or pass into the systemic circulation and reach other tissues. They produce eggs which are passed in the faeces. pigs. the protoscolices attach to the small bowel mucosa and develop into adult worms after several weeks Definitive host: dogs and other canines Intermediate hosts: sheep.and cattle-raising countries Life cycle: The adult tapeworms.200 AD) interpreted this aphorism as describing an hydatid cyst which had burst into the peritoneal 319 . non-nucleated. horses. germinal layer. the larva grows. When ingested by an herbivorous or omnivorous animal. where possible. ? mebendazole or albendazole AWARENESS OF THE ANIMAL NATURE OF HYDATID CYSTS Hydatid cysts have been known since ancient times in both animals an d humans. buds develop from the inner layer and become vacuolated to form brood capsules. humans Major clinical features: manifestations of a space-occupying lesion. 3-6 mm long. proven at operation Treatment: surgery. laminated layer and an inner. During the ensuing months to years. the cystic form of the tapeworm. Sometimes. Taenia hydatigena) in the abdomen of butchered animals. however. They were usually ascribed to being either (1) excrescences or growths in the viscera produced by collections of serum and mucus. He recorde d a case in which attempted paracentesis of the abdomen was hindered by blockage of the trocar and cannula wit h vesicles. with the consequence that echinococcal cysts in humans needed to be separated from similar non-parasitic tumours. are contained in the place where ascites is found. came th e realization that some of these "bladders" wer e really worms.8 Hydatid cysts were noted from time to time in medical works of th e succeeding centuries but their true nature was not generally understood. full of fluid. for he wrote: "The liver is very muc h inclined to produce hydatids in the surrounding fascia. Galen was also familiar with echinococci and cysticerci (probabl y Cysticercus tenuicollis. the liver of slaughtered animals is full of them" 47. after a small discharge of the fluid. Within each cyst. Aretaeus of Cappadocia was also aware of hydatid cysts in humans. cysticerci and coenuri. (3) following the discovery of lymphatic glands in the seventeenth century. Fasciola hepatica. were differentiated. a bladder within will block up the passage. of which this is the proof. It was not until near the end of the seventeenth century that an awarenes s began to dawn that some of these cysts were animal in nature. Moreover. but they also float in a copious fluid. he noticed that the free cyst s moved independently. Francisco Redi.320 A History of Human Helminthology cavity. for if you perforate the abdomen so as to evacuate the fluid. This caused him to comment "quasi animalia foren t proprio motu arta" 98 meaning that the cysts moved about on their own as if they were animals. he found cysts (probably Cysticercus pisiformis ) in the mesentery and also lying free in the peritoneal cavity of a hare. as the liquid within the cysts did not coagulate when he boiled it. in contrast to his earlier observations on the behaviour of eggs in mammalia n . Once this had been achieved. and had noted previously in the livers of sheep. He thought this was unlikely. sometimes mixed with pus . that he had found in the biliary system of the same rabbit. on watching the cysts closely. a s distended and varicous lymphatics. The Italian.spontaneous movement. Observation s were made on a variety of cysts in animals and humans. The problem was compounded by th e common practice of using the term "hydatid" in medicine to refer to any cystic swelling. this circumstance indicated puncture of an echinococcal cys t containing daughter vesicles: Small and numerous bladders. the various species of cysti c worms. Working in Florence in 1684. he observed a retracted neck. including echinococci. appears to have been the first person to both observe and record this phenomenon. The clue that some of these cysts were of animal origin was that many o f them had one of the cardinal att ributes of living animal creatures . between laminae of cellular tissue. Redi wondered whether these cysts could possibly be the eggs of the worms. First. (2) enlarged and degenerated glands or. realizing the similarity of thes e various cysts from different animals. which had just died and was still warm. he found cysts that he called "vesicular hydatids" (probably Cysticercus tenuicollis ). which neck. When one of these was incised and pressed gently. his students. he told a meeting of the Royal Society that "Hydatides i n Animalls are a sort of Living creatures" 115. it moved with a singular form of undulation. the whole bladder being filled with a Limpid water he supposed might be as the stomach to the worm.Echinococcosis 321 ovaries (in which he had found that the enclosed liquid did congeal). East Prussia (now Kaliningrad. this time in a pig (Cysticercus cellulosae . In 1688. the innermost having a neck of a more Opake and solid substance that the rest of the Bladder. Thormann an d Litius. Redi also discovered a similar cyst in a marten and. He recounted his observations o n bladders about the size of a pigeon's egg that he had found in the peritonea l cavity of a gazelle brought from Aleppos (now Halab. he was again to find a motile cyst. found more bladder worms and verified his observations. Philip Hartmann. exhibiting contraction and expansion with rising and falling of its parts. He is recorded in the Journal Book of the Royal Society as describing the bladders in th e following terms: They were found involved in two coats like the corion and the Amnion. then in 1694 h e found Cysticercus fasciolaris in a mouse54.115 Tyson was said to have come to the conclusion that "(they") are worms sui generis or at least the Embrios of them" 115. In th e omentum of a dissected goat.52 The sac itself consisted of nothing beyond a very thin membrane which wa s very smooth on both surfaces and contained a clear liquid lymph within it. was brought to the dissecting room. In the following year (1685). This remarkable insight of Tyson's that the cysts loosely termed "hydatids" were worms or at least the embryos of . In this animal. Syria). white. a professor in the University of Königsberg. He wrote that at once "the rounded tail of a protruding intestina l worm became evident" 52. (at its first being taken out of the Animall) was observed to move as if alive. These early observations were unknown to the Oxford physician. Edwar d Tyson. On the following day. another goat. In February 1687. when he rediscovered such movements in Cysticercus tenuicollis . the largest being greater in size than a chicken's egg. so he placed the specimen in a container of warm water an d reported that: When it was submerged and clinging to the bottom. he thought that he had noticed som e movement. Furthermore. clearl y demonstrating movements while the cysts were still within the membran e formed by the enclosing omentum 52. see chapter 13). He noticed a small. I saw not only the proboscis but also the vesicular body begin movement in a marvellous manner. USSR). grouped them together under the nam e "Glandette o vesichette verminose" meaning "wormy glands or cyst s (vesicles)" 98. globular appendage at the extremity of each cyst. it was turned inside out. emphasized the animal nature of these cysts and clearly related them to intestinal worms. white protruberance. together with the title which he gave it. the consensus of his remarks in the text of th e manuscript. Just how long it took for the recognition of the animal nature of hydatid and other verminous cysts to penetrate the general consciousness of the medica l profession is illustrated by the proceedings of the London Medical Societ y published in The Lancet as late as the year 1833: . Similarly. In that year. and are usually to be met with in rotten Sheep which are usually Hydropical. Tyson then went on to give his clinical experience wit h hydropical bodies occurring in humans. Never theless. and those I take to be of another kind" 116. He thought this unlikely since he had found man y such structures that were all in a similar state when dissecting "rotten sheep". he did not think that all such cysts were necessarily verminous i n nature. I call them Lumbrici Hydropici 116 Although less definite on this occasion by including "or Insects" in his opinion on the nature of hydatids. viz. whereas he would have expected that som e of them should have been in a more mature state if they had been a developing insect. and because they contain so much water in them. and described accurately the small head within each cyst 81. Hartmann and Tyson. Morgagni 84 recalled the researches of Redi.322 A History of Human Helminthology them. Despite the major importance of all these observations and the considerable impetus that they could have given to the elucidation of the nature of the cysts and the life cycles of these organisms. recognized the vitality of cysts he found in pigs ( Cysticercus cellulosae). are a Species of Worms. but only a transparent bl adder fill with a Lymph. with the bladder being the amnion and the outer coa t representing the chorion. He observed that whenever a candle was brought near the cyst . moved. probably unaware of the discoveries of his contempories. Marcus Malpighi in 1697.: " Lumbricus hydropicus or an Essay to prove that Hydatides often met with in morbi d Animal bodies. for he also wrote: "in some I have not observed this Neck and Structure of Parts. the neck. He named these cyst s Lumbricus hydropicus in the following words: These Hydatides therefore I cannot but think are a sort of Worms or Insects sui generis. and pointed out that th e bladderworms described by various authors were not all of the same kind. or Imperfect Animals" 116 leaves little doubt that he considered that hydatid cysts were most likely worms. some of which were undoubtedl y echinococci. predated by more than 150 years the experimental demonstration tha t bladders are the "embryonic form" or intermediate stage in the development of tapeworms. This newly found comprehension of the animal nature of these cysts was largely ignored or forgotten by naturalists and the medical profession until 1760. more than 60 years were to pass before another significant advance was made. Further details of these observatio ns are provided in Tyson's definitive report published in 1891 (the delay being due to difficulty in publishing th e Philosophical Transactions of the Royal Society )116. Tyson canvassed the possibility that these cysts represented an egg or embryo of an insect. a small. Stephens. he managed to separate cystic worms from serous cysts.' he observed. AND THE DIFFER ENTIATION OF SPECIES At almost the same time as Redi. pulpy cysts which members had encountered previously in sheep and in humans. Get a little warm water and see if it will revive the movements. for. RECOGNITION OF THE MORPHOLOGICAL SIMILARITIE S BETWEEN CYSTS AND TAPEWORMS. unfortunately. they are now expiring.Echinococcosis 323 Mr. Secondly. Although Wepfer was the first person to establish a link between any species of tapeworm and its intermediate cystic form. news of this observation was not disseminated widely and it fell into oblivion. he was completely unaware of the life cycle of the parasite and merely considered C. affording the members an opportunity to personally witness the existence of life in these 'imperfect animalcules' as Baillie terms them. though the hydatids shown on this occasion will almost justify the employment of the less equivocal term 'animal'. and though now almost spherical. have assumed an alternately contracted and bulging form. but they had this afternoon as free and perfect movement as a lively leech. Again. to exhibit to the Society three or four hydatids which he procured in the course of the afternoon. Not only did Wepfer r ecognize the animal nature of the cyst. 'Gentlemen will please to be very careful in examining them lest they break and the fact of life shut from our observation. 'as it settles a point greatly in dispute. This interpretation was facilitated by the fact that the caudal vesicle of this cysticercus is relatively small and the head of the worm is not invaginated into it (hence it has has also been called a strobilocercus) . The President immediately drew attention to the exhibition. which were not E. warm water was procured and motion was demonstrated when the cysts were placed in it. It is possible that this parasite may have been seen some 20 years earlier by Pecquet 90. Hartmann and Tyson made the observations already described. but he did not at that time appreciate fully the significance of the observation. Johann Wepfer. granulosus. These cysts. fasciolaris as an encysted tapeworm. In 1766.' Mr. he renewed awareness of the morphological similarities betwee n cystic worms and the heads of tapeworms 89.' 2 Thereupon. Firstly. Stephens entered the room in some haste. but he also realized that it resembled the tapeworm then known as "lati s lumbricus intestinorum". 'Most probably it will not. a Swiss physician and pathologist. He propounded a theory that al l . had been obtained from the mesentery of a sheep and considerable discussion the n ensued as to the relationship between these transparent cysts and the semi opaque. Here is a head as clearly as a head can be. 'This is very interesting. respectively . Peter Pallas made two major contributions to our knowledge o f cystic worms. dis covered in 1688 a cyst.' The President. in the liver of a mouse121. later to be known as Cysticercus fasciolaris. by classifying "hydatids" into non-adherent and adherent forms. When thes e were opened in turn.324 A History of Human Helminthology these cystic worms belonged to a single species which he named Taenia hydatigena. he differentiated verminous from non-parasitic cysts. Within some of the rather hard and leather-like vesicles. He was aware. especially in relation to the circlet of hooks and the sucking pits. any more than Tyson would have claimed that they owed their genesis to roundworms or tapeworms when he used th e term. The requisite evidence was first given in 1782 by Johann Goeze when he described the scolices o f echinococcal cysts and indicate d their similarity to the heads of tapeworms. though. On 1 November of the previous year. however. to describe these parasites. Goeze disce rned a greyish-white. Although Pallas regarded echin ococci as being related to tapeworms. Pallas still believed that they were derived from the latter . such as those oftenest found in pathological cavities in the liver. he proposed that worms in different animal host s varied in their appearance. he noted the resemblances between the cysts (C. and reemphasized the relationship between them and tapewor ms. He recognized that the cyst walls did no t encompass a distinct neck and head. taeniaeformis). in re-awakening interest in t hese cysts. Pallas made two major contributions. but occurred occasionally in humans as well. for example. Pallas was still convinced that these cysts owed their origin to tapeworms: It seems to me very probable that the incompletely developed water vesicles seen by many observers in the human body. Moreover. and the Echinococcus as being closely related to if not ident ical with it. he was unable to discern their true nature. he was unable to provide proof to substantiate this view. he surmised that the heads of the coenuri may be but a further development of th e corpuscles or globules that occurred in echinococci. Lumbricus hydropicus . Similarly. Goeze was given an extremely mutilate d sheep liver that was so permeated with watery vesicles of various sizes that it was almost impossible to see the liver parenchyma. but contained instead a large number of small bodies or corpuscles. Even so. rathe r perplexed by the cysts we now know as echinococci. He knew that they were found most commonly in the liver and lungs of sheep and oxen. Furthermore. he regarded the Coenurus as a many-headed tapeworm. Similarly. granular material which . liquid rushed out like a fountain. are caused by and arise from a worm resembling our own tapeworms. I n fact. In doing this and in adopting the nomenclature.89 Although these cysts appeared to be different in almost every respect from his T. that the cysticercus found in the liver of mic e (C. soft. but since he was able to observe them only macroscopically. he found smaller. fasciolaris) was reminiscent of the head of the cat tapeworm ( Taenia crassicollis now called T. Taenia hydatigena. When he pricked some of the vesicles. bluish vesicles. especially in the structure of the caudal vesicle. hydatigena). hydatigena. he did not mean to imply that these cysts were derived from tapeworms. Thus. Pallas was. he considered that the Coenurus of sheep had the same origin. tenuicollis) found in ruminants and the heads of som e tapeworms of dogs and cats (now called T. In 1800. was a small. From this point. Rudolph i divided the genus Echinococcus into three species. Goeze named them Taenia visceralis socialis granulosus. simiae and E. there was considerable confusion and disput e . then in 1803. Being less than convinced of thei r animal nature. 49 Goeze concluded. Rudolphi in 1801 had erected the genus Echinococcus 99. E. that they were verminous. he gave them the name "acephalocysts" 71.Echinococcosis 325 was connected to a very delicate membrane. Later. When part of this membrane was placed in water. the granules dropped off immediately and appeared to swim around individually. At first. Thus. or else be of a completely different nature. meaning the tapeworm which was found in the viscera and contained a multitude of granules 49. which was later to be placed in this latter order. and that they were related to tapewo rms. The Index Catalogue of Medica l and Veterinary Zoology has cited this parasite as Echinococcus granulosu s ([Goeze 1782]) Batsch 1786) Rudolphi 1805. in front four suckers and on the rounded foreshortened proboscis the exceedingly small double-hook crown. he saw plainly that they were true tapeworms: he bodies were flat and dotted black. that these cysts were a kind of tapeworm whic h were distinct from the coenuri that were found in the brain of giddy sheep . he found many thousands of these granules which were so small that they were hardl y visible to the naked eye. and sheep or cattle. He could not find the familiar taeniid heads seen in hydatid cysts from sheep and oxen. with Rudolphi in his 180 5 paper100 describing Taenia hydatigena granulosa in swine. he renamed them Polycephalus echinococcus 123. there was now no doubt that echinococcal cysts were alive. In the succeeding decades. he called echinococci. Indeed. On examining them with a magnifying glass. this view was generally accepted until Livois showed in 1843 tha t acephalocysts were but ordinary hydatids in which the scolices had not ye t developed 78. therefore. The views of Zeder were perpetuated by Rudolphi in his major text of 18081810. respectively. sloping indentation like an anus. however. Meanwhile. sub-human primates. which he believed infected humans. the size of a pigeon's egg. hominis. Batsch renamed the parasite Hydatigera granulosa 13. veterinorum. He placed the tapeworms in the Order Cestoideorum while the cysti c worms were located in the Order Cysticorum 101. a genera l retrogression occurred. Shortly afterwards (1786) . The name was derived from a combination of th e Greek words (ECHINOS) and (KOKKOS/ COCCUS) meaning "spine" and "berry". however. thus separating them as a zoological entity from th e tapeworms 122. unfortunately. Polycephalus hominis 122 . In one of the vesicles. so concluded that they must either belong to another genus. E. progress in the understanding of the nature of cystic worms ceased for more than half a century. Zeder erected a distinct classificatory group for the cystic worms. respectively 101. posteriorly. on each one. The problem was then compounded by Laennec (1804) who investigated hydatid cysts i n humans. Because of Laennec's authority. hominis" had been discovered in cattle by Haubner and Creplin and that von Ammon had found " E. Rudolf Leuckart at first followed this cl assification and proposed the names E. the same animal or human may have cyst s with or without daughter cysts and that the number of hooklets on each scolex is extremely variable and is dependent. DISCOVERY OF THE ADULT WORM AND ELUCIDATION OF THE MODE OF TRANSMISSION THE BACKGROUND The discovery of the life cycle of E. Thus.326 A History of Human Helminthology among helminthologists. Furthermore. it was eventually realize d that. E. altricipariens in which daughter cysts were formed as well 69. others allowing two. however. the parasite was finally named E. and concluded that it was no longe r proper to separate the two species 87. to some extent. granulosus becomes comprehensible only when viewed in the light of earlier studie s investigating the life cycles of related tapeworms and cystic forms found in a variety of animals. Küchenmeister believed that tw o species of these cysts could be distinguished on morphological grounds and he divided them into E. The most common practice. simplex and E. following a single infection. Naunyn showed that adult tapeworms derived from E. and into E. some admitting the existence of only a single species. veterinorum was thought to occur in animals and have a double row of hooklets. secondly. believed that the same kind of scolex was recovered from hy datid cysts of man as was seen in hydatid cysts in animals 19 . while E. scolicipariens in which scolices alone were present. With the recognition that there was but one species of both the cystic form and the adult worm. upon the age or stage of development of the scolices 16. altricipariens were identical with those obtained from E. . however. Bremser. Firstly. Küchenmeister in 1855 considered that this view was untenable for he believed that "E. In 1863. granulosus since the genus Echinococcus of Rudolphi remained valid and the specific name reverted to the Taenia visceralis socialis granulosa of Goeze. This unitarian view was also adopted by Diesing who named th e worm Echinococcus polymorphus 41. veterinorum" in the human eye. th e morphological similarities between parts of certain cysts and the heads o f various tapeworms had to be recognized and. Nevertheless. for example. scolicipariens. hydatidosa for these two forms. hominis supposedly occurred in man and had scolices with a single row of hooklets. the theory of th e alternation of generations needed to be formulated. Two ideas wer e required to pave the way for the necessary experimental studies. was to divide echinococcal cysts into two species. while yet others thought that there was an even greate r number of species. respectively. Goeze came very close to the truth regarding the development of C. in each of which there was a pisiform vesicle. 1780. but on this as yet. crystal vesicles. the morphological resemblances between the heads of cystic worms and tapeworm heads had been first noted in the latte r part of the seventeenth century by Wepfer. Wagler proposed that tapeworms of cold-blooded animals should be fed to other cold. a number of investigators re-assessed their ideas. At around the same time. no body. then almost one hundred years later by Pallas and Goeze. instead of going into the intestines of their natural hosts . they ignored the labours of their predecessors. the head of the asexual cystic worms possesses such a striking similarity to the heads of certain tapeworms. then watched to see if they became degenerate o r acquired novel properties from their new host. somehow arrived in the tissues. therefore. It is surprising that Steenstrup did not connect the cystic worms with tapeworms as not only had Pallas and Goeze recognized the relationship. two clear. for reasons which it is difficult to perceive. expressed similar convictions. Goeze's friend. He surmised that they were formed by the germs o f tapeworms which. von Siebold in Breslau. that these worms should no longer be classified a s a separate group. and under the influence of this unusua l dwelling-place. Germany (now Wroclaw in Poland). its suckers. that one is tempted to believe that the cystic worms are nothing else than undeveloped and larvae-form tapeworms. As he later recounted. Steenstrup argued. and its circlet of hooks. developed abnormally to become cystic worms. just as he maintained that certain asexual trematodes such as Cercaria species should also no longer be categorized separately. FS Leuckart and F Müller had already recommended the abandon ment of this unnatural cleavage of cystic worms from tapeworms. Indeed. The second impetus was provided in 1842 by Steenstrup when he formulated his theory of the alternation of generations 112 (see chapters 2 and 4). I found in the liver of the mouse.Echinococcosis 327 As has already been discussed . but a number o f other authors including Nitzsch. I have surprised nature in the act. he regarde d them as "une sorte de monstruo sité"42. Küchenmeister summed up the reasons for the general failure of helminthologists to appreciate the connection betwee n cystic worms and tapeworms when he wrote: Naturalists either did not correctly comprehend the true direction of progress.and warm-blooded animals and vice versa.69 As a consequence of Steenstrup's promulgation of his doctrine of th e alternation of generations. fasciolaris when he wrote: On the 13th March. or. H e conjectured that the cystic worms were early stages in the development o f helminths that were unknown to him.104 Von Siebold thought that the adult and larval f orms of the worms must be found .50 Following the same line of thou ght. Dujardin in France in 1845 asserted that cystic worms were incompletely developed tapeworms. von Siebold initially had held the simple (and correct) view that: In its form. I believe that as regards the production and development of this kind of worm. however. 102 Von Siebold voiced this view repe atedly and vociferously. was ignorant of the writings of earlier workers. crassicollis (now known as T. This so annoyed Küchenmeister that he went to great lengths in his textbook to demonstrate that von Siebold was decidedly in error in this claim 69. von Stein . and claimed. von Siebold either conveniently forgot. he hypothesized that if the egg found its way into the intestine of an unsuitable host. that he was the first person to draw attention to the similarity between cystic worms and tapeworms 107. even as late as 1853. which. In another paper. according to von Siebold. T. the head would develop but that the hind part would become inflated and the scolex would sink into it. incredibly. demonstrated in 1853 a similar development of a small bladderworm in th e larva of the mealworm (Tenebrio molitor) that this sequence of events became generally accepted. In 1850. Moreover. without developing sexual organs. Thus. that by virtue of their gross distension. they cast off the degenerated segments.107 This idea was partly engendered by his false belief that. th e jointed mature tapeworm (which he called "strobila") would develop and grow without interruption. have become aberrant and dropsically degenerated.e. von Siebold's championship of the theory of dropsical or cystic degeneration of tapeworms was to lead to an acrimonious difference of opin ion with Küchenmeister. but when their host was devoured by a cat and they became transplanted into their "proper soil".109. fasciolaris. he expounded this theme once more: I finally became convinced that all cystic Entozoa are nothing else than undeveloped or larval tapeworms.328 A History of Human Helminthology in different animal hosts "since the young brood was so seldom seen near the cestodes"103. crispus. frequently strayed into rodents and there degenerate d dropsically (i. filled with fluid) into C. fasciolaris of the mouse. all of the many other cystercerci have deg enerated so far into a dropsical state. He then changed his mind about the development of these cyst s and arrived: at the most decided conviction that the cystic worms are strayed tapeworms which have remained undeveloped and become degenerated. they were no longer fit to return to the state of sexual maturity and consequently they perished without descendents 105. taeniaeformis). then the scolex appeared. the scolex end of the larva was formed first th en this developed a posterior (caudal) projection which in turn underwent secondary hydropic degeneration. Furthermore. that first the cystic caudal end was formed. returned to the normal form of T. thu s . On the other hand. and of which the body grew out in foreign soil into a vesicle. or else. It was not until the Prague zoologist. Vo n Siebold seems to have been unaware that Goeze had already shown in the case of C. Von Siebold then went further and claimed that with the exception of C. arrested in their wanderings. and possibly C. in bladder worms. certain eggs of the tape worm of the cat. fasciolaris of the mouse. crassicollis and arrived at sexual maturity. the Belgian zoologist. PJ van Beneden theorized that the head of a tapeworm (which he named "scolex") is produced from the egg of a tapeworm and conjectured that if the egg reached the gut of a suitable animal host. Nevertheless. and returning to the normal form of T.107. In fact. Between 18 March and 9 April 1851. crassiceps. did not meet with universal acclamation. Küchenmeister fed 40 C. pisiformis to a fox then recovered young tapeworms which he called initially Taenia crassiceps 65. Thus.66. fasciolaris and reported the same phenomenon with Coenurus 106. then finally as T. an eminent University professor. and en raged by Küchenmeister's treatment of his theory of dropsical degeneration of strayed tapeworms. Küchenmeister emphasized the importance of hypothesis and experiment for helminthology and thus became the major figure in the renaissance of this field of scientific endeavour. He concluded that cysti c worms were not strayed. Küc henmeister indicated that cystic worms were an essential stage in the development and maturation of taeniae. This correct view was not accepted readil y because the evidence that he advanced was slight. dropsical tapeworms as claimed by von Siebold. he successfully reared tapeworms in dogs from C. were simply larval tapeworms. In any case. which had hitherto been regarded as a separate class of helminths . He then gave C. His firs t reports in 1851 65. become sexually mature. but when their hosts are eaten by cats and the worms are thus transplanted to their fit soil. This was the state of affairs when Friedrich Küchenmeister in Zittau. C. despite the absence of laboratory facilities and technical and financial assistance. he showed that when cy sticerci were fed to an inappropriate host. serrata. In the great tradition of Redi . they cast off their degenerate joints. annoyed that he. fasciolaris to a cat and again succeeded in rearing tapeworms that were rapidly approaching maturity 67. fasciolaris. pisiformis n. fasciolaris of the mouse. van Benede n was wrong in thinking that eggs developed directly into tapeworms and tha t bladderworms were an unnecessary stage and appeared only incidentally. however. then as T. Shortly afterwards. van Beneden deduced that bladderworm s (Cystici). tenuicollis of domestic mammals and from Coenurus cerebralis of sheep68. had bee n upstaged by a mere general practitioner and amateur parasitologist. Furthermore. crassicollis. Von Siebold. but were tapeworm larvae furnished with a vesicle which probably acted as a reservoir of nutriment.Echinococcosis 329 forming a cysticercus 14. the cysticerci died and no development took place. partly because he first identified the tapeworm that he had reared in foxes as T. (now East) Germany began to investigate the effects of administering various cystic worms to different animals. sp. (which is its current name) .66. pisiformis and C.110 . lost little time in repeating the latter's experiments. crassicollis go astray in rodents and degenerate into C. Küchenmeister began with two of the most easil y accessible cysticerci. he clung to his theory: Some individuals of the brood of T. but he found time to pursue his studies in the midst of running his medical practice. pisiformis of the rabbit and C. Not only did he lack the intellectual milieu in which t o discuss his ideas and concepts. One cannot but be impressed by the perspicacity of this remarkable man and wonder about the driving forces which impelle d him to seek the truth. In 1852 he confirmed the metamorphoses of C. serrata in the gut. cellulosae. Küchenmeister responded in kind saying: "no-one has so grievously offended in the study o f cestodes as the professor of zoology" 70. to every unprejudiced critic. . it should be noted that the idea that all of these cysts were derived from T. he always found T. serrata. Küchenmeister may have used strong words. dropsical worms. but he also came eventually to the view that with the exception of echinococci. the whole theory of the process of metamorphosis would have been thrown into such a state of con fusion that it could hardly have been corrected 107. Thus. was not an original observation. In th eir own experiments. pisiformis of rabbits. to depart from that calmness of tone which becomes scientific contro versy. serrata and that the dog was not a favourable host for the development of some cysticerci such as C. He concluded that the nature of the cyst is determined by the species of host in which the T. van Beneden. cellulosae of pigs and C. degenerated."109. serrata larvae find themselves. The only feasible explanation for this amazing error on von Siebold's part is that his dogs were coincidentally infected with T. This in turn. utterly unfair"76. As we have already seen. Firstly. To this. These false observations reinforced his incorrect belief that cystic worms were a pathological st ate rather than being a physiological necessity for continuation of the life cycle 109. he harked back repeatedly to an earlier comment in his article "Parasiten" dated 1844 102 (although it actually appeared in 1845) on the similarity between cystic worms and tapeworms. he sided with von Siebold: "Küchenmeister in his book underrates von Siebold's share in the solution of the problem in a way which is. They also criticized the experiments of Küchenmeister. including their belief that the experiments were "too successful". but there is no doubt that his experiments opened the door to the t ruth and his interpretation of the results thus obtained were correct. Pouchet and Verrier recovered more tapeworms than the numb er of scolices that they had given. von Siebold embarked upon a personal attack on Küchenmeister and tried to claim credit for himself for the discovery of the phenomenon in two ways. In passing. von Siebold claimed that w hen he fed C. It must also be remarked in passing that not on ly was von Siebold wrong with his theory that cystic worms were strayed. drew the following riposte from von Siebold: "(Küch enmeister) has been led away by his zeal. C. Küchenmeister attacked von Siebold's claims t o priority in drawing attention to the relationship between cystic and tapeworms and castigated his theory of dropsical degeneration 69. When Leuckart came later to review this contre-temps. serrata was one of the points which Pouchet and Verrier used a fe w years later (1862) to attack the whole concept of cystic migrations o f tapeworms. he tried to impai r Küchenmeister's credibility by asserting that if he had not come to the latter's aid in determining the species of the adult tapeworms. C. cerebralis of sheep to dogs. Secondly. von Siebold and others on other grounds. this. tenuicollis of cattle. all the cystic worms were derived from one species of tapeworm which he called T.330 A History of Human Helminthology At the same time. as we have already seen. all wit h extended heads which were placed deep between the villi. nana 15. consisting of a head and two or three posterior segments. the worms were found to have d eveloped further...Echinococcosis 331 and claimed to obtain two distinct species of tapeworms after feeding a single coenurus to a dog. which had a head and three posterior segments containing reproductive organs and eggs. von Siebold called Taenia echinococcus. and then undergo transformation into a vesicle. thinking that they were a new species. I suspect that this might be due in part to the small size of this species of tapeworm and in part to the short time span which is required for its sexual maturation. Finally. which engenders numerous scolices. It was von Siebold who first achieved success. He began his invest igations in the summer of 1852 and re ported his results in the following year 108. 108 These adult worms had in fact been noted earlier by a number of observers. He obtained hydatid cysts from sheep. 93 Nevertheless.that species of adult tapeworm to which the larval Echinococcus brood belongs seems to have escaped the eyes of the helminthologists until now. veterinorum must adapt well in the duodenum of the dog is the elongated state in which the Echinococcus larvae are seen there after feedings. In a dog which was killed 12 days later. but Pouchet and Verrier remained recalcitrant saying: we cannot believe that a microscopic embryo of a taenia enclosed in the intestines of a sheep can make for itself a passage up into the brain of the ruminant.. vo n Siebold discovered mature worms several millimetres long. In 1808. They looked littl e different from the original larvae within the echinococcal cysts except that they were longer and more slender. the growth of the same which follows soon thereafter. then saturated milk with echinococcal larvae and poured it down the throat of a number of dogs. but he did not realize wha t they were53. this was the last gasp of the sceptics and the views of Küchenmeister and others became generally accepted. This induced van Bene den to return to the fray to refute their views. Leuckart an d . When another dog was killed 22 days afte r infection. Hartmann may have seen them as early as 1694. Wagner (1854). GRANULOSUS ADULT WORMS By 1852. but the entire small intestine was lined with innumerable small echinococcal worms. enough was known to stimulate feeding experiments with echino cocci. and summarized his findings thus: Proof that the brood of the E. van Beneden (1857). no worms were found in the stomach. They were seen again in 1850 by van Beneden who. 27 days after infection. EXPERIMENTAL GENERATION OF E. described them in 1852 as T. cucumerina (= cateniformis = Dipylidium caninum) formed by spontaneous generation from the intestina l villi101. Von Siebold's experiments were soon repeated and his results confirmed by Küchenmeister (1853). Rudolphi discovered them in the intestine of a young dog and regarded them as the immature heads of T. These. and finally the production of eggs and embryos in those body segments having reached sexual maturity. 332 A History of Human Helminthology Nettleship (1866). T. Not only did this discovery clarify much of the life cycle of this parasite. but it paved the way for resolving the longstanding battle over the identities of echinococci occurring in various hosts.87 These results were confirmed soon afterwards by Krabbe and Finsen working in Iceland (1866) 64. Naunyn not only confirmed that echinococcal cysts of human origin undergo the same process of development as do hydatid cysts of animal origin. altricipariens. but incubation periods of up to 11 weeks were required. Australia (1883) 114. Vella and Levison to rear adult echinococcal tapeworms in the intestines of dogs from cyst s obtained from humans failed. On 17 February 1863. also showed that there was but a single species. which had received a smalle r number of worms. Th e other dog was killed five weeks after infection. all of whom used hydatid cysts obtained from humans. These were in turn given to a healthy sheep on 25 July 1853.. Ercolani. then a few years later by JD Thomas in Adelaide. Germany. the patient die d from what was said to be typhus and autopsy confirmed the presence of a large hepatic hydatid cyst with well-preserved daughter cysts.. mature. Zenker... Such an experiment was first undertaken by Küchenmeiste r with the parasite he knew as Coenurus cerebralis (= T.. One dog.this Taenia originates from the scolices of the human Echinococcus. Success finally attended the efforts of Bernar d Naunyn working in Berlin. pigs and cattle transformed in the intestines of dogs.. multiceps). echinococcus 87. it was also requisite to show their development fro m tapeworm eggs. but in demonstrating that the adult worms obtained from the two sources were similar. These investigators showed that echinococci from sheep . When the animal was killed three days later. a large hepati c cyst was punctured and the fluid drained. this was thought to be E. As a result of his experiments. they must be considered identical.. echinococcus living in the intestine of the dog.therefore. was killed 28 days later. Liquid containing a few hundred scolices was taken from this cyst and administered to two dogs..and. small tapeworm s identical with the known Taenia echinococcus were found in the small intestine. Shortly thereafter. EXPERIMENTAL GENERATION OF HYDATID CYSTS To prove beyond all doubt that cystic worms were necessary steps in th e development of taenia. First he procured coenuri from a sheep then administered them to a dog in order t o obtain mature proglottids of the tapeworm. Naunyn reached the following conclusions: since these taeniae in all known characteristics correspond to the Taenia echinococcus von Siebold. the Echinococcus of man is the bladder-worm stage of T. Sixteen days later. 15 small coenuri wer e . Thus.coenurosis causes "staggers" i n sheep). the sheep became affected with vertigo (dizziness and loss of balance . Initially.. but no worms were found. all attempts by Küchen meister. Unfortunately. none of them were sufficiently developed for him to be sure that they wer e echinococcal cysts 55. Success finally crowned the efforts of Leuckart in 1867 75. Thes e nodules had a thick.35 mm in diameter. Haubner of the Veterinary School i n Dresden. Leuckart was similarly able to produce Cysticercus fasciolaris in the livers of mice after feeding these animals with eggs from T. After 19 weeks. homogenous capsule enclosing semisolid. It was observed that eggs hatched in the stomach then the liberate d larvae bored through the walls of that viscus or the small intestine and entered the radicles of the portal vein and were carried to the liver. Cysticercus pisiformis . Cysticercus tenuicollis and Cysticercus cellulosae by these investigators 68. crassicollis from a cat. The experiment was then repeated in collaboration with Prof. the echinococcal cysts were 10-12 mm in diameter. At around the same time. tubercular-like nodules 0. Similar results were obtained with Coenurus cerebralis. STUDIES OF THE MIGRATION AND DEVELOPMENT OF LARVAE Two major series of investigations which did much to clarify the details of the migration of larvae and the deve lopment of cysts were undertaken in Paris then Rouen in France by Felix Dévé 34. De w observed larvae in the portal vein within eight hours of feeding ova to pigs 37.35. Some larvae penetrated the hepatic filter and passed to the lungs. This sequence of events . and at the expense of the government of Saxony. echinococcus and was able to make careful naked eye examinations of the resulting cysts at intervals afte r infection. he noted that the liver wa s studded with small.Echinococcosis 333 found on the surface and in the substance of the brain. granula r contents. then Dévé and Dew r outinely infected many experimental animals. initial attempts to replicate these results with echinococci were unsatisfactory. Although a number of investigators in the middle 1850's were able to produce a variety of cysticerci and coenuri by feeding eggs to appropriate animals. A few of the larvae managed to escape through this second net and enter the systemi c circulation and lodged finally in the peripheral tissues. By eight weeks after infection. and in Melbourne. In one pig four weeks after feeding. Australia by Harol d Dew38 . the parasites were 1 mm in diameter. echinococcus and found immense numbers of small vesicles resembling cystic worms in the various organs on dissecting the animal a f ew months later. showed slight lamination of the outer layer. Haubner came close to success when he fed a pig with eggs of T. and were most frequent in the interlobular spaces and beneath th e peritoneal coat of the liver. possessed a well-marked inner germinal layer and contained fluid which escaped from it on puncture. Subsequently. Krabbe and Finsen successfully infected sheep wit h echinocococcal eggs. He infected four suckling pigs with ova of T. Indeed. the elastic laminated cuticular membrane was developed and the nuclear material which comprised th e germinal layers of the cyst was scattered irregularly on its inner surface. and the rest wer e scattered throughout the rest of the body.334 A History of Human Helminthology fitted with the observed distribution of cysts in the human body. daughter cysts were found within hydatid cysts. even within the same organ in the same subject. together with lysis of adjacent liver cells. Many observations were made on the mode of development of scolices and broo d capsules from this membrane by Huxley (1852). and bacterial infection of cysts. although this was denied by others. Subsequent surveys such as those of Thomas114. Dévé34 and the "Australasian Hydatid Register "23 largely confirmed this distribution. nearl y 50% of cysts were found in the liver. at the expense of non-pulmonary hydatids. Th e brood capsules began as small masses on the germinal layer which vacuolated and formed scolices on their inner surfaces 36. These features were more apparent a t three months and the young cyst was beginning to be surrounded by a fibrous adventitia derived from the host. i.e. He studied the microsc opical appearances of echinococci in the livers of suckling pigs from as early as 12 hours after infection to as late as 150 days37. but considerable differences of opinion existe d until the position was clarified by Dew who carried out a series of invest igations in the 1920's. this was followed by a marked infiltration of eosinophils into the follicle . It wa s Naunyn in 1862 who first showed that daughter cysts could arise directly from the germinal membrane or from brood capsules 86. an accumulation of mononuclear cells was observed around the lar vae. T hese series also showed that a third or more of patients had multiple cysts. Davaine25 analysed reported cases and noted that in 373 cases. Goeze had observed a granular coat lining the interior of echinococcal cysts. John . but the germinal membrane was first properly described by Goodsir 51. Scolices an d brood capsules did not appear until at least six months after infection. Rasmmussen (1869) and Leuckart (1885). That he was correct. He also claimed that th e daughter cysts could develop from sco lices. They undoubtedly grew faster in soft tissues but usually took between two and many years to grow large enough to produce symptoms. bein g composed of an outer laminated layer and an inner nuclear layer usually containing brood capsules and scolices. As early a s 1860. Occasionally. 10% in the lungs. they were replicas of the original cyst. Even at the earliest time period. entry of chemical s such as bile or urine into a cyst. the great English surgeon and anatomist. In the late eighteenth century. Vesiculation commenced in the second week and the follicle wall becam e marked more clearly into layers by four weeks. Naunyn (1862). Dévé and Dew both brought forward evidence that suggested that daughter cyst formation may be stimulated by environmental influences including trauma. was proven subsequently by Dévé. Observations over many years in both humans and experimental animals showed that the rate of growth of these cysts was extremely variable. except that a larger proportion of cysts were found in the liver. This view was criticized by Charcot and Davaine on theoretical grounds. The Icelandic physician. In 1898. but wa s revived by Bright in 1861 20 and by Petain and Volkmann (1877). In 1889. Moreover. Dévé demonstrated that. remarking that echinococci never form daughter cysts in sheep. they continued to develop int o fully-fledged hydatid cysts 74. or both that produced secondary cysts. Lebedev an d Andreev showed that if young daughter cysts were released into the peritoneal cavity. he injected brood capsules and scolices from a sheep hepatic cyst intraperitoneally into two rabbit s. This experience led Dévé to believe that daughter cysts probably arise most commonly from scolices. Joh n Hjaltelin. summed this up when he wrote in 1869: (The) symptoms are variable. Similarly. In a later study. first formulated the idea that pelvic hydatid cysts were often secondary to rupture of a visceral cyst and were not the result of multiple infections 59. Dévé then performed a series of experiments which put the matter beyond all doubt. This still begged the question as to whether it was brood capsules. from daugher cysts. hydatid cysts do not die when they ar e punctured and the fluid drained 27. This rule holds good. brood capsules an d individual scolices 38. Dévé produced hydatid cysts in many organs by intravenous o r intra-arterial injection of living scolices alone 29. This has been known from time immemorial. and consist mainly in the functio laesa of the affected organ. Alexinsky in Russia injected hydati d "sand" (brood capsules and scolices) into the peritoneal cavity of seven rabbits and eventually recovered echinococcal cysts from four of the animals 1. that is. Hydatid cysts (althoug h their true nature was unknown) were found frequently in slaughtered animals which had seemed perfectly health y while alive.30. number and location of such cysts. it wa s appreciated gradually that most o f the clinical manifestations of echinococcosis were due to pressure effects on adjacent tissues. and were thus dependent upon the size. in the same series of experiments. RECOGNITION OF THE CLINICAL FEATURES One of the most striking features of echinococcosis is the fact that infectio n with large cysts may be completely asymptomatic. nine or ten small secondary echinococcal cysts were found in the peritoneal cavity of one rabbit and in the injection track in the subcutaneous tissues and in the omentum of the other rabbit26. At the same time. On dissection 16 weeks later. contrary to previous opinion. all of whom warned surgeons about the risk of sowing hydatid elements by puncture of a fertile cyst. scolices. according to the seat and the size of the parasite. echinococcal cysts were encountered from time to time at post-mortem examination of humans who had not complained during life of symptoms that could be ascribed to the parasite. . On 21 September 1900.Echinococcosis 335 Hunter. Dew repeated Dévé's experiments and concluded that secondary cysts may b e formed in all three ways. New Zealand. about the size of feta l heads. . major suppurative complications as a result of secondary bacterial infection wer e recognized. He was asymptomatic until 1926 when he developed recurrent bouts of abdominal and lumbar back pain. returned to work as a shepherd. In 1939. Perhaps the longest duration of infection on record is the case of an English boy aged 11 years who had an abdominal hydatid cyst removed in St. wh o have suffered with echinococci in sites ranging from the heart (sudden death) to the bones (fracture). and he weighed 17 stones (108 kg). After three or four years. in the spine. Among the more doubtful ones was the claim of Dévé tha t echinococcosis caused infantilism and that this condition could be improve d when the cysts were removed. By the age of 39 years. In addition to pressure effects. His health deteriorated to the point where surgical advice was sought. After two to three years. often fatal. two masses of cysts were found in the liver and small. At operation in 1927. may occur in echinococcosis. Two years later. he migrated to the United States of America. for he became acutely ill for several weeks. daughter cysts varying in size fro m cherries to coconuts were evacuated filling bucket after bucket and at least 11 gallons (50 litres) were removed. the n gradually recovered. Much more substantial was the appreciatio n around the turn of this century (at the same time that an understanding o f allergic reactions began to dawn) that anaphylactic reactions. were excised 11. or in one of the abdominal organs. London in 1882. his abdomen measured 57" (145 cm) in girth. Ten weeks later. it was noted that the natural history of echinococcosis tended to have a slowly progressive. At operation. Peritoneal flu id was aspirated and shreds of hydatid cyst were found. in the organs of the chest. a mass was felt in the right upper quadrant of his abdomen. but the patient refused operation for another 13 years until 1943 when the two cysts. and 56 years after the initial operation. the patient. certain toxic reactions to echinococci began to be recognized. Many patients have been recorded. chronic nature. however. he fell on a large stone and may well have caused a hydatid cyst to burst into the peritoneal cavity. Bartholomew's Hospital.336 A History of Human Helminthology whether the hydatid exists in the brain. now weighing many stones less. The majority of patients have complications arising from echinococcal cysts of the liver44. while pulmonary echinococcosis has proved to be the secon d most frequent problem 12. two cysts were observed growing in the abdomen. however. When he was a child of si x years. his abdomen gradually became more prominent and continued to increase in size slowly over the next 30 years. at the age of 67. Perhaps the largest cyst or accumulation of cysts ever recorded was in th e case of a farmer from near Otago.58 Since these cysts grew slowly. isolated lesions were scattered around the peritoneal cavity 72. Finally. particularly when echinococci ruptured either spontaneously or as a result of trauma such as diagnostic aspiration. Weinberg then compared the two procedures. a cyst has ruptured into the lungs or into th e biliary or intestinal tracts and the tell-tale grape-like daughter cysts have been coughed up or passed in the faeces. The first skin test for echinococcosis was described in 1911 by Casoni who used carbolized. and did much to standardize the assay 120. Nevertheless. such as parts of a hydatidiform mole discharged from the uterus per vagina. for they are negative in up to a quarter of patients wit h proven infection. Magath described an immediate reaction occurring within a fe w minutes of application of antigen 80 then this was confirmed as a more reliable diagnostic indicator by Dew and his colleagues 40. a mass thought to be an abscess has been lanced and daughter cysts have extruded through the wound. For all of these reasons. this discovery was of only of limited value. Following the discovery by Goeze in the late eighteenth century of the pathognomonic scolices and hooklets. however.Echinococcosis 337 DEVELOPMENT OF DIAGNOSTIC METHODS The diagnosis of echinococcosis has always been difficult. This was followed in the next year by the demon stration by Fleig and Lisbonne of precipitating antibodies in the sera of persons with hydatid disease46. An alternative approach has to been to try to define the hydatid cyst b y radiological techniques. these methods have had little chance of allowing the clinician to be completely confident about the nature of . Similarly. this fremitus or vibration is produced by loosely-packed daughter cys ts shifting within the mother cyst. and are falsely positive in another small proportion o f patients. The first serological test was reported in 1906 b y Ghedini who described a complement fixation antibody assay using hydati d fluid from human cysts 48. particularl y when diagnostic aspiration of suspected echinococcal cysts fell out of favou r because of the risk of causing secondary echinococcosis or precipitating a n anaphylactic reaction. Rarely. it became possible to be certain of the diagnosis. but there are no embryoni c forms which issue forth into either the bloodstream or the excretions and which might be searched for. attention turned during the early years of th e twentieth century to developing immunological tests to assist in the diagnosis of echinococcal infection. for other lesions hav e sometimes been mistaken for echinoc occi. but they have remained only ancillary aids. they have proved useful adjuncts to diagnosis in th e right clinical setting. favoured the former. Much effort was made over the next few decades to improve these diagnostic tests. Nevertheless. he noted the delaye d inflammatory reaction which developed some hours after immunization 21. Nevertheless. since not only does the parasite itself remain hidden in the tissues. Suc h observations have not always been reliable. Some writers in the nineteenth century placed grea t reliance upon the sign of "hyda tid thrill". Ten years later. it is so rare as to be of little practical value 10. filtered antigens from the fluid in a sheep hydatid cyst. although until recently. Selective angiography began to offer possibilities i n the diagnosis of liver echinococci. morphological delineation of daughter cysts may make the diagnosi s almost certain. whole body CT scanning and magnetic resonance imaging. Some of the most eminent surgeons and physicians in London were consulted and it was decided to keep the abscess open for drainage by insertion of a silver tube.338 A History of Human Helminthology a space-occupying lesion. but now also ultrasound examination. In May 1668. despite the absence of histological confirmation of the presence of echinococcal tissue. surgery has remained the mainstay of the therapy of echinococcosis. over a century later. Hydatid cysts of the liver were particularl y difficult to characterize. and Bonetus in 1697 recorded the case of a patient with a liver cyst which discharged more than 200 vesicle s (daughter cysts) when it was opened 18. THE SEARCH FOR EFFECTIVE TREATMENT Despite many attempts to find anthelmintic drugs active against hydatid cysts. Chest radiography revolutionized the ease wit h which pulmonary echinococcal cysts could be discovered and observed. this happy outcome ought never be relied upon in place of surgery113. first nuclear scanning of the liver. Not only can these latter two techniques be used in any anatomical region. On the other hand. but has largely given way to non-invasiv e techniques. during one of his lectures on the principles of surgery: "When known to be a bag containing fluid it may be opened. but I would not be in a hurry to d o this"60. surgery has consisted simply of puncture and drainage of a cyst. Another famous case from the sam e century is that of the Earl of Shaftesbury who was treated by his persona l physician. On 12 June it wa s opened by cautery and a large quantity of purulent matter containing "man y bags and skins" was discharge d. The experience of Aretaeus at the beginning of the Christian era8 has already been alluded to. John Locke (cited in 88). another surgeon declared that although it is well-known that cysts occasionally die and atrophy resulting in "spontanteous cure". The first problem which all surgeons have had to face was to decide whether attempts at surgical intervention were more likely to do harm or good. John Hunter is quoted as saying. concerning hydatids of the liver. but in some cases. This wa s particularly relevant prior to the advent of modern anaesthesia and surgica l techniques. Shaftesbury had a palpable abdomina l tumour for 12 years before it caused him any inconvenience. he experienced severe abdominal p ain and vomiting then suddenly a soft mass the size of an ostrich's egg appeared in his abdominal wall. Throughout most of recorded history. Contrast radiography was of limited value for hydatid cysts in the gastrointestinal tract and near the biliary tree. This operation became commo n knowledge and Dryden penned the folllowing lines: The working ferment of his active mind . however. In his review in 1910. Other patients developed recurrent hydatid cysts . but that the contents of the cyst wer e killed94. aspiration of fluid contents . He then resorted to dail y injections of iodine for two months. Dévé investigated potentia l echinococcicides in rabbits and showed that injection of 1:100 solution o f mercury perchloride or a 1:200 solution of formol for two and half minute s destroyed the viability of germinal epithelium 28. This latter course became unt enable when Dévé and others at the turn of this century demonstrated experimentally in animals that secondary echinococcal cysts could be induced.Echinococcosis in his weak body's cask confined would burst the rotten vessel where tis bent but that 'tis trapped to give the treason vent. 339 Shaftesbury's operation was successful for he survived another 15 years . there was considerable controversy among surgeons for many years as to whether this was due to se eding of the hydatid material released at operation or not. As surgical techniques improved. and that simple drainage was all that was required 61. were not so fortunate. or obliterating it with sutures. Furthermore. MacLaurin believed that the first course of action was the safest. The opposite viewpoint is exemplified by Hutchinson (1864) who claimed that injection of these compounds increased the risk to the patient. either in the course of the needle track or in the peritoneal cavity. Possi ble methods of dealing with the evacuated cysts included marsupialization (sewing of the adventitia to abdominal wall muscle to allow external drainage). Others. Some surgeons who were concerned about this possibility attempted to kill parasitic tissue by injection of noxious agents after drainage. Even if an apparently solitary hydatid cyst is removed. with gradual resolution of the mass an d recovery of the patient 17. evacuated a larg e quantity of clear serum. filling wit h saline and sewing it up. drainage into the peritoneal cavity. Other substances used for their supposed parasiticidal properties included alcohol and gall. He showed that not only did formalin no t inhibit prompt and complete recovery. The subsequent course was controversial. As has been noted. only time will tell whether ther e . This approach was taken u p immediately by Quénu (1903) who injected hydatid cysts with 1% formali n prior to drainage in three patients. injection of formalin. including the adventitial capsule 7. it became possible sometimes t o remove the cyst in its entirety. One of th e earliest surgeons to do this was Dr Bobilli er of Dunkirk who in 1851 punctured a large swelling near the umbilicus of a 36 year old sailor. but surgeons came eventually to treat each case on its merits in deciding which method t o choose. the standard procedure was to isolate the cyst by carefully packing around it with pads. enucleation of the entire cyst wall (germinal epithelium and laminated mem brane) and swabbing of the adventitious layer with formalin 79. Some patients died from what is now recognized as an anaphylactic reaction precipitated by release of echinococcal products into the tissues. then enuc leated a hydatid cyst of great size by grasping a shred which had presented at the aperture site. By 1910. Currently. some cysts have remained inoperable. or to feed from common plates and dishes. UNDERSTANDING THE EPIDEMIOLOGY The demonstration by von Siebold that dogs were the definitive host o f E. hope was dampened by subsequent experience 6. the prevalence of infection in various intermediate hosts. and mebendazole has not proven to be the answer for the treatment of hydatid infections. retarded the growth of E. believed from his own experience of numerous autopsies. This led to enthusiastic trials with this drug in humans suffering from echinococcal infection. Just as the frequencies of hydatid infections in relation to occupation wer e analysed. and t o analyse the factors influencing the transmission of the parasite. it was realized that the most potent source of infection was the caressing of dogs. therapy with drugs is the only potential alternative.340 A History of Human Helminthology will be a recurrence. These became infected and the resultant adult worms produced multitudes of eggs which were passed in the faeces. that echinococcal cysts could . or as the delayed appearance of a more slowly-growing cyst acquired at the time of the original infection. either as a secondary cyst resulting from spillage a t operation. albendazole. It had long been appreciated that hy datid infection was more common among people with particular occupations such as farmers and butchers and i n members of their families. Dr Thorensen. mebendazole. John Hjaltelin. The next steps were to define the incidence of infection in humans. Although infection may be acquired by children eating dirt or by the consumption of uncooked. allowing them to lick the hands and face. granulosus in white mice and killed th e germinal epithelium 56. it was their common practice to feed the offal (which often contained cysts) to farm and house dogs. considered that about one in seven of the inhabitants were so infected. It became apparent by the middle of the ninteenth century tha t echinococcosis in Iceland had reached e pidemic proportions. In these circumstances . the related compound. Although the success rates of operation have continued to increase over the years. granulosus and the experimental generation by Leuckart of echinoccoca l cysts after feeding eggs to sheep clarified in a dramatic fashion ou r understanding of the mode of transmission of hydatid infection. No drug showed an y promise until it was found in 1 975 that the benzimidazole compound. is under investigation. The reasons for this were now plain. and the frequency of infection in dogs. and one o f his successors. When suc h people killed domestic animals such as sheep and cattle. The Physician-inchief of the country. Cysts are sometimes placed i n locations that make it too danger ous to intervene. or the cysts are so massive or widespread as to militate against surgical assault. Although initial reports were encour aging. contaminated fruit and vegetables or by drinking polluted water. so the distribution of echinococcosis in different countries wa s investigated. For example.. granulosus has been separated into a number of subspecies including E. g. unilocular and sterile. These include transmission between kangaroos an d dingoes in Australia (with the potential for infecting aborigines) and between deer and wolves in Canada. a writer to the Melbourne Argus in Australia observed on 10 May 1874 that: Hydatid disease is endemic in this colony. in Iceland in 1863 .5% of 11. 16. Krabbe found echinococcal cysts in 12. Similarly. high frequencies were noted in a number of other sheep-raisin g countries including Australia. Dévé in 1923 found that in Tunisia. E. nearly all of the cattle. Thus. was a high frequency of infection in dogs. while infec tions were insignificant in goats and pigs31. .5% of 2497 pigs were found to be infected 45. and though not so constantly met with as in Iceland. On the basis of these different intermediate hos t specificities and/or on morphological characteristics. all of these data have provided an ample base on which to evolve effective methods of prevention and control.. While the sheep-dog cycle thus described is the most important epidemio logical scenario.Echinococcosis 341 be found in one or another of the internal organs of nearly every fifth adul t body58. g. Although these subdivisions may be somewhat controversial. This remarkable prevalence was attributed to the intimate relationship between the Icelanders and their sh eep. we may probably claim the doubtful honour of holding the second place in the list of countries so affected. It was thus clear that echinococcosis was a zoonosis with the cycle being maintaine d between dogs and farm animals. For the same reasons. about one third of the estimated 120. canadensis and E. particularly sheep. in Iceland in 1863.. Despite the higher frequency of infection in cattle.257 sheep. a number of other life cycles which may be of local importance have been discovered. New Zealand. 20-60% of sheep and 30% o f camels examined were infected. E. with human infectio n occurring incidentally and playing no part in the continued transmission o f infection. g.5% of sheep 64. cattle and dogs. Similarly. granulosus granulosus . Australia in 1929. E. in a survey in Victoria. It was estimated at that time that in Iceland there were 20 dogs per 100 inhabitants 64. The common occurrence of hydatid infection in humans was found to be coexistent with a very high frequency of infection in certain stock animals. while in New Zealand in 1937. Occurring pari passu with a high prevalence of infection in cattle and sheep.9% of 4922 cattle and 0.To meet with hydatids as a cause of deranged health is now a matter of daily expectation with every medical practitioner. Thus. sheep were of mor e importance in the maintenance of the life cycle of the parasite since the cysts in cattle were commonly simple. Argentina. 23. Uruguay and nations of North Africa and the Midd le East. borealis. 28% of dogs were infected 64. equinus.000 rural dogs harboured adult E. granulosus 9. P erhaps the most important factor of all. He argued that people who slaughtered domesticated animals should not be allowed to throw offal containing bladders (cystic worms) to dogs as food. Leared's paper was translated int o Icelandic by Hjaltelin and published in two newspapers. Leared indicated the effectiveness of kamala in a dog of his own that he brought back to England from Iceland. an English physician. however. however. 73 In a footnote to the document. In 1890. Eschricht's nominee. Arthur Leared. inveighing against foreign interference in the affairs of Denmark. receive the consideration to which they were undoubtedly otherwise entitled. they did not. Leared forwarded his paper to Baron Eschricht. Hjalteli n believed that the plan was "both original and practical" 58 but it came to nought. and drew up a paper detailing his proposal for submission to Dr Hjaltelin. the greater part of which was spent in making some feeding experiments on dogs" 58. and an educational cam paign was conducted throughout the country explaining how the disease was produced and how it might be averted. Küchenmeister in hi s textbook laid down one of the cardinal principles on which the control o f echinococcosis is founded69. Leare d conceived the idea of dealing with the problem by dosing simultaneously all of the dogs in the country with an efficient a nthelmintic. visited Iceland and drew the attention of the country's doctors to the recent German discoveries on the life cycle of echinococci. the capital city (with a quarter of the country's population). the chief physician. In order to effect this . as Leared has recorded: The result was an amusingly intemperate letter. Further. it was necessary to communicate with the College of Health i n Copenhagen. so characteristic of his writings. This proposa l was placed before the Diet where it was rejected as unsatisfactory. the head of the College. no r should raw fruit or vegetables be eaten where there was a chance that the y could have been contaminated with eggs. and stating that he would himself undertake to send a competent person to Iceland to investigate the subject. then Hjalteli n undertook to have the plan enacted by parliament. Dr. However. was forbidden. perhaps. Denmark (Iceland then being a territory of that country). however. All Krabbe could suggest as a preventive was to kill a great number of the shepherds' dogs. The keeping of dogs within the boundaries of Reykjavik. water should not be drunk unboiled. a law was passe d controlling dogs by taxation and ensuring their treatment with anthelmintics and enforcing the burial of material potentially contaminated with echinococci. He concluded that kamala was the most efficient taeniacide available. perhaps because: his sentiments were expressed in a tedious and diffuse style. who was also a member of the Legislative Assembly. Since dogs were indispensable to the farmers.342 A History of Human Helminthology THE EVOLUTION OF PREVENTIVE AND CONTROL MEASURES Just two years after von Siebold's epochal discovery.77 In 1862. . Krabbe was despatched from Denmark "for a very short time. These suggestions were not widely taken up. Perhaps immunization of animals may eventually become a practical proposition. MULTILOCULARIS During the first half of the nineteenth century. thus giving cysts insufficient time to reac h maturity43. but are sometimes condemned to ignoble use" 9. OTHER SPECIES OF ECHINOCOCCUS E. prohibition of feeding raw offa l to dogs. Educational pro grammes alone often had no great effect. the compulsory intermittent administration of anthelmintics (first arecoline. Campaigns of increasing sophistication were mounted in a number of more developed countries such as Australia and New Zealand. Ultimately. The control of echinococcosis suffered from two major disadvantages compared with campaigns against that other common wormy zoonosis. and the monitoring of the results of these efforts. was a fortuitous change in farming practice. th e number of dogs had fallen to one for every 15 people from the one per fou r persons obtaining in 1890. male lambs were killed at a younger age (4-5 months). Buhr and Luschka. described a peculiar and rar e tumour of the liver which they called "alveolar colloid" or "colloid carcinoma". farmers had no particular incentive to keep their sheep clean of parasites. a number of European pathologists. and later of bunamidin e hydrochloride). The consequences of all these measures were that by 1927. One despairing Ne w Zealander lamented that "It has been re ported to us that our leaflets are not only left unread. This was reinforced by the sever e economic consequences of trichinous infe ction. the active constituent of areca nut. but no-one has yet improved on the unsuccessfu l attempts of Dévé in 1927 to immunize rabbits challenged with echinococci 32. and only 1 in 1500 of the human population ha d hydatid infection 83. including Ruysch. echinococcosis was an infection of low-grade endemicity and did little to penetrate the nationa l consciousness. infection of the viscera had n o deleterious effects on the flesh for food purposes and so did not interfere with the export of frozen meat which was a staple article of the sheep and cattl e trade of many countries 3. but in other countries lackin g sufficient finanacial and technical resources. thes e programmes have been eminently successful. legislation was enacted in some countries embodying the control of dogs. Rudolf Virchow recognized the characteristic hooklets of Echino- .Echinococcosis 343 however. In many places. educational campaigns. however. In 1855. trichinosis. They objected especially to the extra labour involved in boiling offal prior to feeding their dogs. In contrast. echinococcosis continues it s ravages unchecked. Perhaps more importantly. In the latter case. epidemics of fatal infection so alarmed the populace that the legislature was prodded into action. Since the infection had no noticeably detrimental effects on wool and mutton. granulosus was then known). however. In 1931 . which under certain conditions gave rise to th e alveolar form of hydatid cyst. Th e corollary to this was that since dogs do not have access to human livers. th e variety should have become extinct if they were a separate species. some parasitologists. Autopsy four months later revealed two small alveolar hydatid cysts in the lungs of the pig and Mangold believed that thes e results supported the dualist conception 82. Klemm in 1883 fed the Virchow. These worms had minor variations in the size and number of hooklets and the ova were arranged in a different manner. Other authorities took up these points to evolve the "double or dualist theory" that postulated the existence of two species whose larvae had different pathological effects an d whose adults may be differentiated morphologically. He also believed (erroneously) that this type o f hydatid disease was frequent in oxen and its limited geographical distribution was attributable to close association of humans with these animals. the parasite showed characteristics of both an alveolar hydatid and the multilocular form of E. Thus. alveolaris 91. although he did not know the exact means by which man was infected. granulosus. On the other hand. Mangold in 1892 infected a suckling pig with eggs of an adult echinococcal tapeworm derived previously from a human alveolar hydatid. It was then realized. In 1875.344 A History of Human Helminthology coccus in such a tumour and showed that the lesion was not a malignant proliferation but was helminthic in nature. Further more. E. Virchow termed the lesion "ulcerative multilocular hydatid" 117. and the other producing the lesion described by Virchow. Dew reported the first apparent case of alveolar hydatid infection in Australia. still held to th e original single form or "unicyst theory" which held that there was one species of parasite. the size and shape of which determined the nature of the growth. Considerable controversy was to follow. Nevertheless. He suggested that growth took place exogenously (instead of endogenously within a cyst wall) in the lymphatic spaces. granulosus. in particular Dévé. Believing that it was a variation of the larval form of the common Taenia echinococcus (as E. Posselt did not think that the dog was the normal definitive host. Russia and adjacent regions. Switzerland. Posselt regarded these differences as sufficient to justify the creation of a distinct species which he named T. Posselt in Austria repeated thi s experiment in 1904 and obtained tapeworms from a dog fed with an alveolar echinococcal cyst.type hydatid to dogs and could discern no significant differences between the resultant adult worms and th e well-known T. He used this observation to support the notion . one causing the usual hydatid infection. Morin 85 first propounded the view that ther e were two distinct species. echinococcus. The main argument in favour of this hypothesis was that the alveolar hydatids were believed to be confined to humans. he upheld Virchow's statement as to th e unity of the two forms 63. Initially. that this form o f hydatid infection was restricted in dis tribution to Germany. helminthologists followed Virchow's line that there was only on e adult echinococcal parasite. The major point in favour of this theory was the peculiar geographical distribution of the parasite 92. presumably extrinsic stimuli. Ironically. when Vogel re-examined some of Posselt's material. when a cyst from an infected field vole was fed to a dog. In 1955 . granulosus. the valid name for this species was not E. On re-examination. he found that foxes (Vulpes vulpes) in the Serbian Alps were infected naturally with adult Echinococcus. Alveolar echinococcosis was als o found to be prevalent in the Eskimo population on the island and Rausc h speculated that this form was probably identical with that causing alveola r hydatid infections in Europe and in the USSR. it became generally agreed that there were two species of Echino- . Vogel pointed out 119 that on the basis of priority. unlike E. portions of a tumour which Posselt in 1906 had described as an ordinar y hydatid and an alveolar hydatid lying side by side in the heart of a human . granulosus in a number of respects. multilocularis Leuckart 1863. Conversely. Dévé fo und all intermediate stages between the two supposedly distinct forms and decided that the loculative change in the hydatid must be ascribed to some special environ mental effect 33. although it is rather unfortunate as it sometimes lead to confusion with the multilocular form of echinococcosis commonly seen i n cattle and which has also been given the name "multilocularis" but is in fact a form of E. Vogel also determined that. Alaska 97. this parasite also developed in cats and foxes as well as in dogs. Finally. h e could find no major morpholo gical differences between Alaskan and European collections. he found simila r tapeworms in the small intestine of a dog that Posselt had fed with huma n alveolar material in 1901. separate and distinct and with no connection or intermediate morphologica l stages. Rausch and Schiller discovered alveolar hydatid in fections in the tundra vole ( Microtus oeconomus inuitus) on St. Further. Moreover. adult worms were obtained which differed morphologically from E. held in the Innsbruck Pathological Institute. He took the proglottids of these worms and fed them to voles and rats. In 1951. Lawrence Island. and concluded that they were geographical races of the one species. alveolaris but E. from the Pathological Museum in Vienna. including ground squirrels and shrews. A commentator in The Lancet in 1933 felt that at last the matter had been probably settled and stated that: The reasonable conclusion from these facts is that there is one species o f hydatid which occasionally grows in an abnormal fashion as the result o f abnormal. and that the health officer is no t faced with the attempt to devise special preventive measures in the effort to combat infection from unknown strobiles inhabiting an unidentified hos t species. Vogel showed by feeding experiments that the Alaskan and European hydatids were identical118. granulosus. and alveolar echinococcosi s resulted. Dévé then obtained. Thus. Natural infections were the n found in other mammals.Echinococcosis 345 that the two lesions were morphological variants of the larval form of the same adult parasite39. This designation stands today.5 But the dualist theory was not yet laid to rest. granulosus matured in dogs but not in foxes while ungulates were the usual intermediate hosts. It was observed that many patients complained of vague abdominal discomfort succeeded by jaundice. Scolex formation wa s uncommon and occurred only in a few tru e. and eosinophils usually developed as did a n obliterative endarteritis. The quest for an effective anthelmintic has so far not met with success. with E. the parasite tended t o invade blood vessels and spread by metastasis to other organs. led ultimately to the description of a new species. thus simulating a malignant neoplasm.346 A History of Human Helminthology coccus responsible for human hydatid diseases. E. The adjacent liver cells were necrotic. by Rausch and Bernstein in 1972 95. particularly the lungs. Since that time. Although a few patients have been recorded where partial hepatectomy with complet e removal of the parasite has been successful. giant cells. It was found that these parasites occurred most commonly in the liver . lymph nodes and brain. granulosus and E. strains or subspecies that incorporate a number of features of eithe r species111. where the parasites replicated and reproduced the original lesion. The diagnosis was made by liver biopsy. Again like an infiltrating neoplasm. spherical cysts. The cells of the germinal laye r tended to spread out in long outrunners a long tissue planes into the surrounding tissues. more cases have been reported from other parts of Central and South America. Clinical examination revealed that the liver wa s enlarged simulating a hepatoma or secondary malignant deposit. however. Pathological examination of these echinococci revealed that the cysts were often of only microscopic size. epithelioid cells. they did this by feeding parts of the cysts to dogs and recovering adult worms subsequently 24. irregular and lacking in rigidity. E. Subsequent studies have indicated that the natural cycle o f infection is between the bush dog and the paca ( Cuniculus paca). small. it was often imperfect. although primary lesions were disc overed occasionally in other sites. when laminated material was laid down. The problems of speciation may be even more complex. there being no true peripheral encysting layer. but that . whereas E. thus producing central caseation not unlike that seen in tuberculosis. The limits of the parasite were uncertain. a chronic inflammatory reaction of lymphocytes . multilocularis perhaps being at each end of a hypothetical scale encompassing a number o f "races". VOGELI The discovery in a Los Angeles zoo of an unusual proglottid in the faeces of a bush dog (Speothos venaticus) which had been captured recently in Ecuador. vogeli. most patients run a downhill course and die within several years. E. The larval stage of this parasite was first identified in 1979 in two patients in Colombia by D'Alessandro and colleagues. multilocularis matured in cats and foxes as well as in dogs while microtin e rodents were utilized as interme diate hosts. Hydatid disease (hydatidosis). the larva forms a polycysti c hydatid with endogenous proliferation. pp 284. Lancet i: 719-720. Ueber ein neues Operationsverfahren zur Entfernung von Echinococcus in der Leber und anderen parenchymatösen Bauchorganen. Paris. translated by F. Extracted from Mémoires de l'Académie Royale de Belgique de Bruxelles. van BENEDEN PJ. ANONYMOUS. ANONYMOUS. Lancet ii: 304. 1911 . De causis et notis etc. Pulmonary hydatid disease. tica Genevae. L Chonet. The prognosis is frequently poor. The Sydenham Society. CASONI T. 1931 5. pp 1691. BONETUS T.. pp 1706. pp 190. 1852 15. 1861 al 21. Sepulchretum sive anatomica prac ex cadaveribus morbo denatis. ANONYMOUS. van BENEDEN PJ. BARRETT NR. ALEXINSKY JP. New Zealand Medical Journal 36: ce 105-117. couronné par l'Institut. 1851 (Abstract) 18. 1850. Supplement to Comptes Rendu s Hebdomadaires des Séances de l'Académie des Sciences. de leur anatomie et de leur développement. Folia Clinica Chemica e Microscopica 4: 5-16. The extant works of Aretaeus th e Cappadocian. British Medical Journal ii : 593-599. 1898 2. four volumes. but longterm mebendazole therapy is being evaluated currently. Naturgeschichte der Bandwu rmgattung überhaupt und ihrer Arten insbesondere nach den neueren Beobachtungen in einem systematischen Auszuge. La diagnosa biologica dell'echinococcosi umana mediante l'intradermoreazione. London Medical Society: Living hydatids.Echinococcosis 347 domestic dogs could also be infected and are probably the usual source o f infection for humans96. Medical Journal o f Australia ii: 511-514. definitive diagnosis is made by recovery of all or part of the parasite. 1856 9. London. In the paca (a rodent). 1819 20. Hydatid disease and public health. Extraction of a large hydatid growth from the abdomen. Wien. Ein Buch für ausübend e Aertze. Treatment is by surgica l resection where possible. Clinical memoirs on abdomin tumours and intumescence. Archives of Surgery 42 : 1-17. London. BARNETT L. Prevalen and prevention. BARNETT L. ANONYMOUS. ARETAEUS CAPPADOX. 1833 3. Paris. The alveolar hydatid. 1979 7. 1697-1700 19. Halle. Pathology and treatment. British Journal of Tuberculosis 38: 39-95. Medical treatment for hydatiddisease? British Medical Journal ii: 563. Hydatid disease: errors in teaching and practice. Traité de zoologie médicale. BARNETT L. REFERENCES 1. Mit nach der Natur gezeichneten Abbildungen auf vier Tafeln. Some problems of hydatid disease. Archiv für klinische Chirurgie 56: 819-826. Ueber lebende Würmer im lebenden Menschen. Lancet ii: 583. Abstracted in British and Foreign Medico-Chirurgical Review 10: 322-335. 1941 8. but in humans. Carl Schaumburg und Comp. Hydatid disease. 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Teubner. 1782. 53. 1864 62. KRABBE. GOEZE JAE. Vermes vesiculares sive hydatoides in caprearum omentis et in pulmonibus arterius furfuracea. Lancet ii: 178-180. principalement ceux qui se trouvent dans le corps humain. KÜCHENMEISTER F. HUTCHINSON J. pp 68. Versuch einer Naturgeschichte der Eingeweiderwürmer thierischer Körper . Jo hannis Ernesti Adelbulneri. p 299. The hydatid disease in Iceland: a few remarks on district-physician Joh n Finsen's contribution to our knowledge of the disease. Decuriae II. HUNTER J. De anatome canis hydropici. Decuriae II. GOEZE JAE. Cited in 16 52. KÜCHENMEISTER F. Anni 1694. Parasitology 70: 273-285. 1695 54. Nuremberg. KÜCHENMEISTER F. Versuch einer Naturgeschichte der Eingeweidewürmer thierischer Körper . Zeitschrift für klinische Medicin 4: 448-451. Cited in 76 71. 1939 . The lethal effect of mebendazole on secondary Echinococcus granulosus. Partly translated in 62. GOODSIR. HUNTER J. Cited in 69 56.Echinococcosis 349 liquido in essa contenuto. diagnosis and treatment. Annus Quarti Ann i MDCLXXXV (1685). Miscellanea Curiosa Sive Ephemerb idum Medico-Physicarum Germanicarum Academiae Naturae Curiosorum. 1853 69. A manual of their natural history. pp 152157. Leipzig. 1978 63. Miscellanea Curiosa Sive Ephemeridum Medico-Physicaru m Germanicarum Academiae Naturae Curiosorum. Leipzig and Frankfurt. 1852 68. Blankenburg. 1851 66. Experimente über die Entstehung der Cestoden Zweiter Stuf e zunachst des Coenurus cerebralis. KÜCHENMEISTER F. Decuriae III . Einiges über den Übergang der Finnen in Taenien und über da s Digitalin. 1866 65. cysticerci of Taenia pisiformis and tetrathyridia of Mesocestoides corti. 1855. 1857 70. Ein Lehr. Gazzetta degli Ospedali et delle Cliniche 27: 1616-1617. 2 volumes. 1869 59. Vorläufige Mittheilung(Über Cysticercus pisiformis der Kaninchen). Echinococcus cysts of the liver of fifty six years' duration. London. 1948-1953 58. Translated in 62. Ithaca. 1906 49. Partly translated in 69. pp 677. British Medical Journal i: 197-201. Cornell University Press. Mémoire sur les vers vésiculaires. Journal of th e American Medical Association 112: 1331-1333. 1793. Recherches helminthologiques en Da nemark et en Islande. Medical and Surgical Transactions 1: 35. PA Pape. Anni 1694. Annus II. London. Miscellanea Curiosa Sive Ephemeridum Medico-Physicarum Germanicarum Academiae Naturae Curiosorum. Classic investigJ. Cited in 34 60. Cited in 4 61. translated by WH Jones and ET Whithington. four volumes. translated by E Lankester. Animal parasites belonging to the group Entozoa. 51. Loeb Classica l Library. Die in und an dem Körper des lebenden Menschen vorkommenden Parasiten. pp 471. HEATH DD. pp 1-27. LAENNEC RT. pp 176. HARTMANNUS PJ. Heinemann. GEC Gad. 1975 57. Zeitschrift für klinische Medicin 2: 295-299. KLEMM H. pp 486. 1851 67 KÜCHENMEISTER F. Under Mitwirkung des Herrn Professor Haubner au f Befehl und Kosten des hohen königliche sachsischen Staatsministerii des Innern. pp 452. KEAN BH. Blankenberg. 1782. CHEVIS RA. Cuniculus paca L. American Journal of Tropical Medicine an d Hygiene 30: 1043-1052. 1853 94. RAUSCH VR. 1921 81. QUÉNU E. NAUNYN B. Münchener medizinische Wochen schrift 53: 537-541. 1843 79. Hydatid disease (echinococcosis) in Alaska and th e . 1867) 76. MATTHIASON S. Zur Stellung des Alveolarechinokokkus. Berliner klinische Wochenschrift 29: 50-55. (Rodentia: Dasyproctidae). (pp 1-256. volume 2. Ueber den multiloculären Echinococcus und seine Taenie. SCHILLER EL. pp 334. Hydatid disease in Iceland. pp 1009. 1889. 1908 89. 600-609. 1972 in the natural intermediate host. 1972 96. two volumes. Physiologie und wissenschaftliche Medicin. 1906 92. Oxford University Press . 1867 74. The clinical manifesta tions. Recherches sur les échinocoques che l'homme et chez les animaux. Athens. LIVOIS E. VERRIER. Zeitschrift für Tropenmedizin und Parasitologie 23: 25-34. 1927 84. Leipzig. RAUSCH R. (Cestoda: Taeniidae) from the bush dog. Archiv für Anatomie. LEARED A. translated by WE Hoyle. Translated in 62 88. MORGAGNI JB. Physiologie und wissen schaftliche Medicin. pp 187. Ueber die zu Echinococcus hominis gehörige tänie. MALPIGHI M. 1879-1886. CF Winter'sche Verlagshandlung .und Lehrbuch für Naturforscher und Aertze. D'ALESSANDRO A. Cited in 22 78.. Proceedings of the Third International Congress of Comparative Pathology. Characteristics of the larvalEchinococcus vogeli Rausch and Bernstein. MAGATH TB. LEBEDEV AI. Translated in Archiv für pathologische Anatomie und Physiologie und für klinische Medicin (Virchow) 118: 552-556. POUCHET. Leipzig. An Alabaman student and other biographical essays. Comptes Rendu s Hebdomadaires des Séances de l'Académie des Sciences 54: 958-963. volume 1. Journal des Sçavants 2: 382-385. Echinococcus vogeli sp. Thèse de Berne. pp 612-638. 1936 93. Ein Hand. Thèse de Paris. Technique opératoire contre l'échinococcose secondaire. De sedibus et causus morborum per anatomen indagatis libri quinque etc. 1903 95. Entwickelung des Echinococcus. LEUCKART R. 1766. In Russian. 1688 91. World's Health 8: 408-411.350 A History of Human Helminthology 73. Miscellanea zoologica: quibus novae imprimis atque obscurae animaliu m species describuntur et observationibus iconibusque illustrantur. MORIN A.und Lehrbuch für Naturforscher und Aertze. n. the paca. Opera posthuma. 1863. PALLAS PS. A et J Churchill. 1889 75. Londini. Translated n i Quarterly Journal of Microscopical Science 2: 171-175.. Petersburgh 10: 633-635. YoungJ Pentland. The cystic plague of Iceland. Venetiis. Kystes hydatiques du foie. Oxford. 1875 86. . Bulletin et Mémoires de la Société de Chirurgie de Paris 29: 719-729. NAUNYN B. 1697 82. MANGOLD C. Deux cas de tumeur à échinocoques multiloculaires. RAUSCH R. Echinococcus disease: etiology and laboratory aids to diagnosis. BERNSTEIN JJ. POSSELT A. LEUCKART R. OSLER W. Partly translated in 62 90. Vrach. z p 123. a seipso scripta. Die menschlichen Parasiten unddie von ihnen herrührenden Krankheiten. 1760-1761 85. MacLAURIN C. Die Parasiten des Menschen und die von ihnen herrührenden Krankheiten. 1862. 1867-1876. Medica l Clinics of North America 5: 549-571. pp 27-55.. sur le sujet des vers qui se trouvent dans le foie de quelques animaux. CF Winter'sche Verlagshandlung. Speothos venaticus (Lund). Ein hand. pp 412-416. diagnosis and treatment of hydatid disease of the liver. Quibus praefixa est vita. 1862 87. RAUSCH R. Reports of the Section of Human Medicine. Archiv für Anatomie. 1910 80. ANDREEV NI. P. British Medical Journal ii: 957-961. PECQUET. pp 771. Edinburgh. Lancet i: 337. St. 1981 97. A textbook for students and practitioners.. 1886 77. 1892 83. pp 882. The parasites of man and the diseases which proceed from them. Haga e Comitum. Extrait d'une lettre de M. Petrum van Cleff. Expériences sur les migrations des entozoaires. Remondini-ana. (Transplantation of Echinococcus cysts of man into rabbits). POSSELT A. pp 219. a M. LEUCKART R. Ueber die Natur des Echinococcus alveolaris und seine Beziehung zum Echinococcus hidatidosis. von SIEBOLD CT. 1687 116. Leipzig. von SIEBOLD CT. von SIEBOLD CT. volume 7. REDI F. SMYTH JD. 1884 115. or An essay to prove that hydatides often met with i n morbid animal bodies. Partly translated in 76 104. Experiénce sur la transformation des vers vésiculaires ou cysticerques in taenias. 17: 377-381. von SIEBOLD CT. Lumbricus hydropicus. Philosophical Transactions of the Royal Society 17: 506-510. Ueber den Generationswechser der Cestoden nebst einer Revision de r Gattung Tetrarhynchus. On the alternation of generations. 1853. pp 88 and 90. translated by G Busk from the German translation of CH Lorenzen. en saeregen Form for Opfostringen i de lavere Dyreklasser. 110. Kjøbenhavn. Über den Echinococcus multilocularis Süddeutschlands. The spontaneous cure of hydatid cysts. Cited in 76 111. Paris. von SIEBOLD CT. 1853. the propogation and development of animal s through alternate generations: a peculiar form of fostering the young in the lower classes of animals. Deutsche medizinische Wochenschrift 80: 931-932. 1852 107.Echinococcosis 351 importance of rodent intermediate hosts. 1852 106. Abstracted in British and Foreign Medico-Chirurgical Review 10: 322-335. pp 253. or. On tape an d cystic worms with an introduction on the origin of intestinal worms. 1801 100. Ray Society. Advances in Parasitology 2: 169-219 . Über den Entwicklungszyklus die Artzugehörigkeit des europaïschen Alveolarechinococcus. In. Berlin. VOGEL H. von SIEBOLD CT. Zeitschrift für wissenschaftliche Zoologie 2: 198-230. volume 1. Translated in Quarterly Journal of Microscopical Science 2: 255-263. Beobachtungen über die Eingeweidewürmer. 1857. 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Landmarks in echinococcosis ___________________________________________________________________ Hippocrates alluded to lesions that were undoubtedly hydatid cysts in the abdomen of humans 1766 Pallas hypothesized that human hydatid cysts arose from tapeworms 1782 Goeze described the scolices within hydatid cysts and indicated their similarity with the heads of tapeworms 1851 Bobillier injected iodine into an hydatid cyst 1853 von Siebold discovered the adult tapeworms in the small intestine of dogs after feeding them with larvae from echinococcal cysts obtained from sheep 1855 Küchenmeister argued that offal of slaughtered domestic animals should not be fed to dogs 1855 Virchow discovered characteristic echinococcal hooklets in so-called "colloid carcinoma". multilocularis 1863 Naunyn recovered adult tapeworms from the small intestine of a dog fed with the contents of an hydatid cyst obtained from a human 1867 Leuckart generated hydatid cysts in pigs by feeding them with eggs obtained from adult tapeworms 1867 Leared reported that kamala eradicated tapeworms from the intestines of dogs 1889 Lebedev and Andreev showed that daughter cysts released into the peritoneal cavity of rabbits developed into fully-fledged cysts 1898 Alexinsky demonstrated that cysts developed from "hydatid sand" (brood capsules + scolices) injected intraperitoneally in rabbits 1906 Ghedini described a complement fixation test for serodiagnosis 1911 Casoni described a skin test for immunodiagnosis 1913 Dévé produced cysts by injection of scolices alone 1922-5 Dew described in detail the development of larvae in the tissues 1975 Heath and colleagues showed that mebendazole had some parasiticidal activity in experimental echinococcosis ___________________________________________________________________ c.400 BC .1.Echinococcosis 353 Table 12. where it vesiculates to form a bladder worm (Cysticercus cellulosae). subcutaneous tissues and central nervous system. Should humans ingest eggs. When ingested by pigs. praziquantel 2. usually 2-7 metres in length. visual disturbances may occur Diagnosis: 1. the larvae hatch and pass to the tissues in the same manner as they do in pigs Definitive host: humans Intermediate host: pigs Major clinical features: 1. surgery if necessary and possible AWARENESS OF THE ADULT WORM AND DETERMINATION OF ITS NATURE Tapeworms have been known for generations. intestinal taeniasis: finding of eggs (any Taenia) or proglottids (T. intestinal taeniasis: abdominal discomfort. cysticercosis: suggested by radiography and other imaging techniques. live in the small intestine with the head attached to the mucosa. Tapeworms were prevalent in ancien t Egypt and were probably mentioned in the Papyrus Ebers. serology. cysticercosis: epilepsy. They were alluded to by a number of writers at the beginnings of recorded history. solium) in the faeces 2. dating around 1550 355 . these usually reach 5-10 mm in size and contain an invaginated head. the head evaginates in the small intestine and develops into an adult tapeworm which produces eggs after approximately 3 months. When ingested by a human.Chapter 13 Taenia solium AND TAENIASIS SOLIUM AND CYSTICERCOSIS SYNOPSIS Common name: tapeworm Distribution: cosmopolitan but absent from Australia and some parts of Oceania Life cycle: the adult tapeworms. Individual proglottids o r segments of worms are so obvious that pr ehistoric man must have noticed them and wondered about their origin. Eggs and gravid proglottids are passed in the faeces. eggs hatch in the small intestine and each released larva (oncosphere) penetrates the mucosa and passes via the bloodstream to the tissues. spontaneous passage of proglottids 2. cysticercosis: praziquantel. especially the muscles. proven by excision biopsy Treatment: 1. intestinal taeniasis: niclosamide. Tapeworms wer e described by the Greeks including Hippocrates (460-375 BC) 51. but also because pumpkin seeds were one of the earliest remedies for tapeworm infection.85. qui solium sive cingulum dicitur.550 AD) and Paulus Aegineta 1 (c. have been Taenia saginata since. whereas others. the Arabians. according to Herodotus. including Ibn Sina (Avicenna . This view was disputed by . Early writers had various ideas about the nat ure of these worms. in fact. which are the worst.1300 A D) who wrote: quidam dicunt quod isti cucurbitini generantur in ventre cujusdam maximi lumbrici qui aliquando emittitur longior uno vel duobus brachiis. 105 Romans such as Celsus (c. but believed that it was a membrane formed by the intestine to hold these cucurbitini. worms also occasionally take possession of the bowel. the Armenians. These were named cucurbitini.The Thracians have it not.800 AD) regarded th e individual tapeworm proglottids as distinct worms 99. "Lumbricus" was a group term meaning "worm" and "latus" meant "broad" or "wide". at another more nastily from the mouth. the parasites may. these worms were apparent to peoples in many other parts of th e world. including India and China and mention is made of them in the Asia n ancient literature 52. at times to be rounded. Aristotle (384-c. Thus.322 BC)8 and Threophrastus (c.. but Aetius 2 (c. Hippocrates. Aristotle and Galen regarded the tapeworm as an animal. Many Arab writers did not consider the whole tapeworm as a worm at all. and we observe them sometimes to be flattened. Speaking generally.111 According to Nicholas Andry ..372-286 BC) who called them eithe r µ (HELMINS PLATEIA) meaning "flatworm" or (TAINIA. the ancient Egyptians did not eat pork. Among the Hellenes.the Egyptians.640 AD) thought that a tapeworm represented a transformed strip of intestinal lining.200 AD)41 recognized tapeworms and named them "lumbricus latus". In the latter part of the first milleniu m after Christ. Thus. those Thebans who frequent wrestling schools and the Boeotians generally are liable to it: but not the Athenians. the following are liable to it .. nor the Phrygians. Galen wrote concerning intestinal worms: Again.356 A History of Human Helminthology BC32. Pliny the Elder (23-79 AD) 20 and Galen (129-c.20 AD) 24.41 Similarly. Threophrastus remarked: This worm (flatworm) naturally infects certain races. some Arab authors such as Serapion (c. not only because of their resembl ance to pumpkin seeds ( Cucurbita species). He wrote that the worm was "called solium from its being the only one of its species in the body" 4. and these are discharged at one time from the lower bowels. The name taenia "solium" was apparently first used in relation to tapeworms in a publication by Arnaldo Villanovani (Arnault de Villeneuve. TAENIA) meaning "band" or "ribbon" worm. c. this expression was already in verbal use before Villanovani's time and reflected the erroneous belief that a person could only be host to a single tapeworm. 981-1037 AD) thought that cucurbitini (pumpkin seed worms) and taeni a (gigantic worms) were completely different creatures 10. Taeniasis solium and Cysticercosis 357 Leuckart. in the following year. It fell to the Englishman. including Spigelius104 and Amatus Lusitanius. Krehl postulated that schuschl-e had become transformed into solium via Arabic then French or Spanish authors of th e Middle Ages: "Among the Arabians it would be changed into susl or sosl. 107 Tyson was fortunate in not only having a number of patients who suffered from tapeworm infections. Tyson. professor of oriental languages at th e University of Leipzig. was the discovery that tapeworms had a head. despite their most diligent enquiries. such as Tulp 106 and Fehr37. the Italian. which has created as many controversies among Anatomists of late. at the Anatomical Theater of the College of Physicians. independently published small-scale and rather crude illustrations of the heads of dog and cat tapeworms 90. Some. It was the finding of tapeworms in the intestines of dissected dogs that allowed him to orientate the worm in the bowel correctly and gave him access to th e whole worm. than that of this Worm. on the grounds that the Latin word for "single" or "alone" is "solus" whereas "solium" means "seat" or "throne" 66. could not come to any certain conclusion as to the orientation of the worm within the body. as well as to a proper under standing of the nature of these parasites. Simpler ones could be invoked equally well. Although Platter was ab le to discern differences between the strobiles of Taenia and Diphyllobothrium (see chapter 15). . near the end of the seventeenth century. but that: "I should like to offer as an explanation the certainly somewhat Syriac word for tapeworm. the key to the definitiv e separation of the various tapeworm species. Francesco Redi . and obscure to the Ancients. eloquently summed up th e current state of knowledge: The head of the Nile does not seem to be more plerplex't. Edward Tyson. Others . who reported: "It is impossible to derive the word solium from the classic languages" 61. This explanation seems a bit far-fetched. to make this fundamenta l discovery in 1683107. even described and illustrated heads that were not heads at all . however. Others again. i. as that has with the Geographers of old. did not take the setting of the worm segmen t in relation to the intestine into account and were misled into describing the more slender end as the tail. namel y Schuschl-e (properly 'chains')"61. where I observed this worm alive in the Ilion. but in encountering such worms in a variety of animals. Many earlier anatomists had noticed a difference in the size of each end of a tapeworm segment. then.e. Leuckart therefore solicited the views of Dr Krehl. perhaps the worm has been called "solium" because segments of the worm issue from the "solium" (meaning "seat" or "ru mp") while sitting on the "solium" (meaning the "throne". thus permitting him to find the head: And it was in a Dog I opened at our private meeting. and among the romance authors it would lose the second s" 61. not lying streight. Krehl then went on to say that there were n o appropriate words in either Arabic or Hebrew. Taenia solium was confused with Taenia saginata and Diphyllobothrium latum for two thousand years or more. toilet)! As will be discussed in the next two chapters. Tyson was. Thus. as well as as many other physicians. both ancient and moder n.. and to be the true use of this part we call the head is this. Firstly. and gradually increasing in length. but maintained that it was not a single worm but many worms linked together and enveloped by a lining derived from the intestine. other authors admitted a tapeworm to be alive. whereof the larger did arise from the Center or Middle spreading themselves over the edges of the circumference. Having taken notice how the Joynts were. and convoluted.. parts of the body are sooner broken off. where I expected the head to be.the neck. and solved this dilemm a incorrectly by mistaking the genital aperture in each proglottid for a mouth . and its body in many places winding.. the other which were issuing out about the middle from the Center and were shorter. and therefore to be an Animal and alive" 107. but a little globous and I could perceive. that it was not without some trouble. I traced it up. for he.. which we may suppose to be the mouth. that tapeworms were not living creatures.107 Tyson put the worm in spirit of wine then took it home to examine it at leisure with a microscope. had "observed it to move. and has fasten'd itself to the inward coat of the Intestine. Thereupon.. whether o f . and large too. and small.beset with two orders of Spikes. This sac was deemed not to be animated itself but received its motion from the proglottids (cucurbitini) enclosed within it. by carefully opening the intestine to the smallest Extream. and which did lye towards the Duodenum. for while examining a tapeworm recovered from a dissected dog. very thick set.This end was not perfectly flat. and did nothing adhere. by gently raising it with my Nail.. however. whereas the broader end was free. which is so fast. 107 Tyson also addressed two other questions.For some little space here.It comes away very frequently in pieces. as Hippocrates says. inform myself of any orifice here.. This opinion seemed to Tyson to be wide of the mark.. which we frequently see in the stool. that rather than loosen itself..107 Subsequently... it had been asserted by a number of authorities.. as they descended towards the Tail. he wa s unable to find such a structure in any tapeworm he examined. that I freed it from its adhesion. but after. and so prevent. or Hooks. what seems most agreeable to me. a couple of joints fell off intact..358 A History of Human Helminthology but in many places winding and doubling... whereas that small extream did do firmly stick. by means of these hooks.I could not upon my strictest Enquiry and with extraordinary Glasses too.hence it is that this Worm is of so difficult a cure. Further.... I could not observe with the glasses any Joynts at all. Secondly. he found that the head: very plainly appeared.. had it not this hold.39 Tyson disputed this view.. He was troubled by his failure to observe a mouth in the head of the worm. Tyson found similar hea ds in other tapeworms and was left in no doubt as to the correctness of his observations. on the right track in his assessment of the hooks: Upon the whole. Gabucinus in 1547 wrote: I think the Broad worm to be nothing else. its too easy ejection out of the body. than the white scourings of the Guts within which living creatures like Gourd-seed are bred. and yet there was no evidence of any membrane attached to the remainder of the worm.. the descent of the faeces upon all occasions would be apt to carry it out with them. or Spikes it might fasten itself. For it being so very long. These Eggs are so numerous in the worm. In contrast to the many staunch proponents of the theory of the spontaneous generation of worms.. The next significant advance in the understanding of tapeworms was made by the German. although the latter author quoted Merry (1654-1722) of the Académie des Sciences as regarding them as nasal openings. These errors were perpetuated by other authors and new ones were made . Andry was a firm upholder of the view that worms must develop from eggs. raised more questions as to the nature of the organism. indeed. along with me. and is of Opinion. as did Andry. Thus. He was the first to illustrate the head of a huma n tapeworm (which happened to be T. bu t mistook them for a tracheal system analogous to the tracheal system i n silkworms described previously by Malpighi.. observing instead that it had not been his design to raise a new hypothesis.4 Some later commentators have believed that Andry may have mistaken th e round. The discovery of a head.. He believed that he had descried such structures: We cut up half an Ell (an English ell is 113 cm and a Flemish ell was 68 cm) of it. believed that these suckers were mouths. Tyson himself was perplexed. together with the conclusion that a tapeworm was not a sac containing many cucur bitini. The latter mistake had also been made some years earlier (1697) by Malpighi 75. but very round. van Doeveren (1764) 30.. Malpighi also considered that the suckers were eyes.. that which sticks to the Pin. and thought that the hooks on the scolex were teeth 30. He was also familiar with the uterus and its ramifications. there being four mouths to enabl e sufficient food to be swallowed to sustain the very long body of the tapeworms 17.. but to enquire into the truth of those of others. saginata). would appear to be an incredible Pile of small eggs... like Tyson. and examined it very narrowly. Van Doeveren also considered that tapeworms had no real head but a sort of mouth at one end.M. Rosenstein (1778) 93 and Linnaeus. Bellestre. that if you touch them with the Point of a Pin. and did not venture to give an y definitive answer. but regarded them as pulmonary openings through which the tapeworms took air: "the nipples must be looked upon as so many lungs"4. mistook the genital openings for mouths. on the other hand.Taeniasis solium and Cysticercosis 359 human or animal origin. calcareous bodies in proglottids for eggs. Johann Goeze.. that these are Eggs.We only perceived all over it heaps of small Globular Bodies resembling corns of millet.examined these Globular Bodies.. though no bigger than a grain of Dust. He reported in 1782 that he was able t o demonstrate that the marginal opening at the side of each proglottid which had been mistaken for a mouth or for an airway was in fact connected with th e reproductive system: . he thought that this was a good example of anatomical adaptation to physiological requirements. Nicholas Andry published his observations on the anatomy of tapeworms 4.. Bloc h (1782). He did not follow Tyson's view that the genital pores were mouths.. it being much easier to spy others' faults than to avoid them oneself! A few years later (1700). The absence of a digestive sys tem was confirmed and the presence of a vascular system was defined. As mentioned earlier. he postulated a number of mechanisms.43 Goeze observed eggs in the ovaries and drew rudimentary figures depictin g them. Goeze himself had noticed two smal l openings on each side of every proglottid. There still remained the problem o f defining the nature of the organization or individuality of a tapeworm. In 1835. latum) 34. Was a tapeworm a simple animal with a head and jointed body. or was it a compoun d animal? Most authors considered the tapeworm as a single animal that maintained its hold in the gut by means of the head and fed itself through it. then Sommer a few years later provided further details of thi s system103. whether of human or animal origin. amongst which was the idea that these worms may be hermaphroditic: Are there. Platner and von Siebold. von Siebold had observed that Taenia eggs contained an embryo wit h small hooks100. two sexes amongst them? Or is every tapeworm sufficient to itself and does it fertilize its own eggs? How are the organs for this purpose constituted and where are they?43 Over the next few decades. and wondered how fertilization took place. Some writers believed that th e cucurbitini were held together by an enclosing membrane derived from intestinal mucus. He was particularly puzzled by the fact that he had never seen an y tapeworm. In 1847. Although Goeze did not know th e answer.360 A History of Human Helminthology On the mature lower segments the marginal openings in part project so far that the protrusion and the indented osculum can be seen with the naked eye. th e longitudinal canals that had been recognized as running through the entir e . many of the details of the anatomy of tapeworms were elucidated. others thought that they were glued together. the anatomy of the sexual apparatus w as gradually pieced together by a number of investigators. then in the following year he had discovered Taenia spermatozoa101. many of the ancient Greek and Roman investigators were of the opinion that a tapeworm originate d through the union of separate proglottids. Emile Blanchard discovered the nervous system of tapeworms 16. It was then shown that these vessels were interconnected at the head and descended throughout the length of the tapeworm. In 1841. communicating with each other from proglottid to proglottid at their lateral margins. This view that tape worms were formed by the union of previously free cucurbitini held sway until the end of the 17th century when the heads of tapeworms were discovered . which did not have eggs. a new question arose. Finally. Although this concept was now disposed of. while yet other s believed that they held each other by mouth openings. therefore. Mehlis. and afterwards I pulled off the surface with fine instruments until I saw with pleasure under the magnifying glass that the hair was in the transverse canal that led to the ovary. Eschricht published the first detailed anatomy of a tapeworm ( D. particularly the Germans. each of which traversed the length of the proglottid. Leuckart provided a major analysis of the reproductive system in 1862. I inserted a horse hair. By continued budding there arises from an originally isolated nurse a whole community of individuals . presumably by analogy with the Latin words "index" and "indices".. A n alternative proposition.Taeniasis solium and Cysticercosis 361 length of the worm were thought to arise in the suckers and were regarde d erroneously as an intestine. so have there been differences of opinion over terminology. and as more recently discussed by Arme 9. the so-called 'head'. Similar etymological difficulties confront the user of the word "scolex". respectively. This term was introduced by van Beneden 12 to describe the head of a tapeworm. Strictly speaking. Since it is hallowed by custom. championed by P J van Beneden (1850). but each of which at the same time is provided with all the elements essential to its individuality. I have continued to use "scolices" in this book. and the proglottids or sexual individuals which were usually present in large numbers.. "proglottis" should be used for a single joint and "proglottides" for more than one. According to the Oxfor d English Dictionary. I have followed the practice of the major text on medical parasitology 11 in using the terms "proglottid" and "proglottids" to describe one or more joints. 12 This view was attractive to Moquin-Tandon who wrote that the Taenia is a perfect animal which is composed of a scolex and a number of proglottid s which: constitute special organisms placed end to end and enjoying a community of life. These classica l niceties have been corrupted in many textbooks. Thus. the scolex was considered to be the "nurse" to the strobila .a colony in which one has to distinguish not only animals at various stages of maturity. According to van Beneden: the head (scolex) remains like a true nurse. In essence.. a tapeworm was viewed as a single animal with numerous proglottids which were cast off at the posterior end. to indicate the connecte d series of proglottids. a tapeworm was believed to be a combination of two generations: the scolex which was single and had arisen by asexual multiplication. This word could be derived either from the Greek word (STROBILOS) meaning "anything twisted" or a "pine-cone" o r from (STROBILE) meaning "plug of lint twisted into the shape of . This word wa s derived from the Greek word (GLOTTIS) meaning "tongue". Similar difficulties apply to the term "strobila". but also one asexual and aberrant member. asexual. since the plural of this word is "proglottides". however.78 Just as there was confusion over t he nature of tapeworms. SCOLEX) for a worm. The use of "scolices" as the plural form of this word is firmly entrenched in the literatu re. such usage is erroneous and the rules of Gree k declension dictate that it should be "scoleces". but is commonly used to indicate a number o f proglottids joined together. suggested that the tapeworm was a compound animal of separate individuals. Felix Dujardin introduced the ter m "proglottis" to describe the isolated joint or cucurbitinus. The term "segment" is also vague. Accordingly. This concep t grew out of Steenstrup's theory of the "Alternation of Generations" . It is derived from the Greek word (SKOLEX. also introduced by van Beneden. An Anglicized plural form of "strobilas " could be used. J Rumler in 1558 may have been the first person to describe cysticerci i n humans when he found tumours on the surface of the dura mater in an epileptic person96. especially those of the back. the Englishman Thomas Wharton found large numbers of cysts. none of these observers was aware of the animal nature of these lesions. we will examine boldly and at our ease his wide-opened mouth to see if he is measled. which he took to be glands. it needs to be said that the worm was given its modern zoologica l nomen Taenia solium when Linnaeus placed it in the tenth edition of hi s Systema Naturae 67. Within each cyst. Aristotle knew the chief localizations of cysts in pigs and compared them to hailstones 8. by pulling out his tongue. Perhaps even simpler would be to Anglicize the word completely and use the terms strobile and strobiles for the singular and plural forms of the parasite. Hartmann found a worm. while others remarked upon their resemblance to pearls. although he did not realize that he was looking at a head with its suckers and circlet o f hooks: . alternatively. Arme has suggested that "strobila" could be used for both the singular and plural forms of the word9. "Th e Knights". with the slave Demosthenes suggesting that Cleon (one of the main characters) should be treated in the same way that pigs were examined: Let us force a stake into his mouth as do the cooks. In 1688.362 A History of Human Helminthology a pine-cone" and which became "strobila" in modern Latin. three years after he had described the motion of cysticerc i (Cysticercus tenuicollis) in the omentum of a goat.448-386 BC). Again. Some authorities also cite Conrad Gesner as having described th e parasite in 1558. were pulled out they usually had drops of blood on their roots. It should not be "strobilae" (which would imply falsely a Latin origin). DISCOVERY OF CYSTICERCI The ancient Greeks were well-acquainted with measly pork although they did not comprehend its nature. in the adipose tissue and muscles of a soldier 116. Aristotle considered that infected pigs could not remain standing on their hind legs. but I have not been able to find a specific reference to such a passage. and recognition of this fac t developed pari passu with similar observations made with other cysti c parasitic worms. Finally. Panarolus in 1652 found similar cysts in the corpus callosum of the brain of an epileptic priest83. and attached to its inner surface by bands which he termed the "frustulum". the condition was so well known that he could use it in his play. As discussed in chapter 12." Similarly. there ar e problems with the plural form of this word. and that if the bristles. and then. By the time of Aristophanes of Athens (c. In 1656. Philip Hartmann also found cysts in the heart of a pig. a whitish body which looked like a spiral staircase.Taeniasis solium and Cysticercosis 363 In the heart of a pig I noticed that there were very many cysts.. When Gmelin came to publish his revision of Linnaeus's Systema Naturae in 1790. CYSTIS) and respectively. mostly in the muscles an d choroid plexus.. Treutler. the parasite thus becoming known as Cysticercus cellulosae 95.. an d described clearly their morphology. a small head was erected. Cysticercus. At its extremity. Loschge and Laennec found similar lesions in humans. Rudolphi adopted this generic classification and applied the specific name "cellulosae" of Gmelin. Goeze re-examined the cysts found in pork. to house these parasites 123. While dissecting the body of a soldier who had been in good health but who had drowne d accidentally. recognized that they were helminthic in nature. he found two small cysts. (KERKOS. In 1803. a number of pathologists including Fischer. he recognized a small head and wrote: "in apice atollitur capitulum" 75 meaning that at the apex of this body. these descriptions were eithe r vague or remained unnoticed for many years. Nevertheless. he pointed out the similarities between the head of the worm with in the cyst and that of an adult Taenia found in the intestinal tract of humans 44. Stenbech. This name persisted until the genus wa s abolished when cysticerci were shown to be larval stages of Taenia. Brera. at the end of the seventeenth century. This name was derived from a combination of the Greek words (KUSTIS. . and apparently ignoran t of these earlier reports. In 1786. as well as thei r resemblances to tapeworms. but the term "cysticercus cellulosae" continues to be used to describe the organisms of this type found in pigs and humans. In addition. In 1784. under the pectoralis major muscle.when the capsules were cut open a peculiar skin of thin membrane could be removed. CERCOS) meaning "bladder" and "tail" . Nevertheless. Around this period. Goeze still believed in th e zoological independence of these parasites from tapeworms. Over the next few years. He investigated the structure o f cysts found in measly pork and saw within each vesicle. 48 Marcus Malpighi. and called them Taenia cellulosae 42. These he named "Finna" since they resemble d measly pork which was called "fi nnen" in Germany 115. Zeder created a new genus. Otto Fabricius also recognized the animal nature of measly pork. Werner rediscovered these cysticerci in humans. discovered independently the animal nature of these cysticerci.itself a small worm. and was the first person to speak of the head of a worm within each cysticercus. he accepted the verminous nature of these cysts. each of which contained a worm. He included these wormy cysts among hi s "Taenia viscerales hydatigenae". This covered both a clear liquid and a white filament coiled like a white thread . A few years later. is from all others hitherto observed out of it. Indeed. The origin of tapeworms was uppermost in the mind of Edward Tyson in 1683 when he wrote the paper in which he described the head of a tapeworm. he may well have found the eggs and this could have given him a clue to the origin of the worms. less than an inch long and with very short segments 82. or of the same Species. bred in animal bodys. that are received with the food or other ways. 107 Tyson was completely mystified as to h ow tapeworms could have arrived in the intestines by seeds introduced from the external environment for there were no free-living worms which resembled these creatures and could have provide d spawn: And what I have laid down I think I have made out. yet one great difficulty still remains with me. SOLIUM The origins of intestinal tapeworms were a mystery for most of recorde d history. som e learned authorities still held that they were the products of spontaneou s generation (see chapter 2). out of the body. how to account for several of those that are bred in Animal bodies not such as we may supposed to be hatched from eggs of like kind. T. He introduced the small red eggs of the dog tapeworm. A natural experiment was that reported by Peter Pallas in 1760. One month later. they spewed out what he took to be chylous juice into the receptacle. how different this sort of Worm. from whence any Seminal matter of it. cucumerina (= Dipylidium caninum). Pallas claimed to fin d there small tapeworms. 107 This seemed to him to give some credence to the idea of spontaneous generation and he concluded the title of his manuscript with: "And the whole urged as a difficulty against the doctrine of univocal generation" 107.364 A History of Human Helminthology ELUCIDATION OF THE MODE OF TRANSMISSION EXPERIMENTAL GENERATION OF ADULT T. and their manner of generation. so of late hath been much illustrated by the laborious researches of many inquisitive persons: whose travels therin. some commentators were induced to believe that the ov a must be involved in the generation of adult worms. as it is a subject of curious speculation. it may be supposed to be propogated. If he had examined this material under his rudimentary microscope. and common error. of their production for putrefaction. Tyson believed that the genital pores were mouths and considered that the proglottids became turgid after absorbing "chylous" intestinal contents through these openings . through a small wound into the abdominal cavity of a pup. as late as the early part of the nineteenth century. for he began his discourse in the following manner: The consideration of Insects. No-one was ever able to repeat this experiment and Küchenmeister in hi s . Following the discovery of tapeworm eggs by Andry at the beginning of the eighteenth century. too easily received. When he placed proglottids in spirit of wine. and bid very fair for the exploding of that. tho' they have much advanced the doctrine of univocal generation [i.e. sexual reproduction]. but of whom we cannot meet with a parallel. Taeniasis solium and Cysticercosis 365 textbook of 1855 summed up the general view succinctly: "This is ver y improbable. first pointed out by Goeze in 1784 then re-emphasized by Dujardin in 1845 31. It is very difficult to known how this error occurred. that bot h Rudolphi (1810) and Bremser (1819) actually believed that tapeworm s constituted the strongest argument known in favour of the doctrine o f spontaneous generation (see chapter 2). pisiformis. a number of German investigators including von Siebold i n Breslau. All this was to change with the demonstration that many cystic worms metamorphosed into adult worms in the intestines when ingested by suitable hosts (see chapter 12). administered Cysticercus cellulosae to dogs. the n produced.e. At the beginning of 1853. He himself never succeeded in obtaining mature tapeworms afte r feeding C. was t o feed eggs to animals in order to see if adult worms developed in the intestines. each scolex attached itself to the intestinal mucosa by hooks and/or suckers. Another obvious experiment. C. Taenia hydatigena) 62. (now Wroclaw. This inability to produce adult worms from eggs administered either orally or parenterally. cellulosae to dogs. May in Weishenstephen. Studies with a number of cysticercus/tapeworm systems ha d shown that following ingestion of cysticerci. Küchenmeister thought that von Siebold's tapeworm was probably Taenia ex cysticerco tenuicollo (i. Poland) . cellulosae to humans. Coenurus cerebralis and Echinococcus granulosus into their respective mature forms had already been prove n experimentally. A year of so later. solium from humans and the scolex of C. By 1854. In his experiment. pisiformis (which metamorphoses easily in dog small bowel) in water for ten days made them incapable of further development. tenuicollis. I think a complete mistake" 62. such experiments were entirely ne gative. and Küchenmeister in Zittau. these were then cast off at the posterior end. He obtained permission to administer bladder worms to a murderess under sentence of death. proglottids which became progressively more distinctly jointed and sexually mature. Both von Siebold and May claimed to rear mature tapeworms (which the former called Taenia serrata and the latter believed to be Taenia solium) in the intestines of thes e animals. cellulosae. In view of the difficulties of experimentatio n with humans. Secondly. and. C. the conversion of Cysticercus fasciolaris . however. for Pallas was a very talented and sagacious observer . May had kept his cysticerci preserved in water at 9oC for ten days before feeding. he demonstrated that the incubation of C. but was unable to proceed with the experiment. suggested by Pallas. Finally. assumed a flattened form. suggested that a similar connection might exist between these two forms. an opportunit y presented itself when a convict was scheduled to be executed several mile s . appeared to so confound the doctrine of "omne vivum ex ova" (all life comes from eggs). by budding. Küchenmeister regarded these results a s erroneous. The morphological similarities between the head of a mature T. Küchenmeister determined to examine the effects of administering C. Goeze and others. In reviewing his r esults. Dr D and Dr Z. Not only did he find young larvae with hooklets. the intestines were examined by Küchenmeister and his medic al collaborators in the presence of several professors. Küchenmeister's wife found some C. and Küchen meister believed that those cy sticerci were probably already dead at the time of administration. Since C. therefore.63 Küchenmeister recognized. solium is exactly the same as with all others originating from bladder worms and probably like that of most of the Taeniae (3) that we. solium hominis (2) that the mode of infection with T. solium. and Taenia cystic. T. . Küchenmeister was left in no doubt that all these specimens harboured hooklets of the typ e seen in T. whose names h e was not allowed to publish 63. when compared with other preparations of T. The investigation was undertaken i n collaboration with two medical colleagues. for breakfast. the priso n doctor gave the convict some blood sausage.63 This was examined under the microscope and: we saw a young Taenia with a projected proboscis to which four hooklets pointing forward were loosely attached. however.366 A History of Human Helminthology from Küchenmeister's home. but one was 6-8 mm in length and had an appendage. they found another nine specimens. Most of the worms were 3-4 mm long. proved clearly to be hooklets of the T. Over the next two and a half da ys. he summarized them by saying that the experiment had established: (1) that the C. solium and C. bu t Küchenmeister found a young tapeworm: I was successful in finding a small Taenia which was tightly attached with its projected proboscis to a piece of duodenal mucosa which I had softened in water for a few minutes. No traces of the last feedings were found in the intestines. and after much pleading. solium since cysticercus is transmitted by those foods which we eat raw. ho wever. which had been slaughtered 60 hours previously. cellulosae is the scolex of the T. that th e experiment needed to be repeated with a longer time being allowed for comp lete development of adult tapeworms to occur. tenuicollis from a pig intermingled with noodles in a soup cooled to blood temperature to the convict. from which a few of the fatt y pieces had been removed and a dozen bladder worms inserted.63 Subsequently. cellulosae was not available at the time. pisiformis from a rabbit and C. although the short time at his disposal gav e Küchenmeister scant hope for success. Küchenmeister rushed around to th e restaurant. infect ourselves with T. solium. one of which had the complete classical crown of T. cellulosae and not in the other cysticerci. one of these colleagues gave fresh C. the condemned man ingested a further 61 C. obtained one pound of pork from the pig. serrata vera. solium with 22 hooklets in two rows. which consisted of warm roast pork obtained from a nearby restaurant. Forty eight hours after execution. Next morning. In an attempt to head off any adverse criticis m of the ethics of the experiment. cellulosae in their evening meal. cellulosae in sausage or soup. tenuicolli. Three and a half days before the convict's death. these. so that he received the bladder worms without knowing it. In this instance. cellulosae. he was able to infect the subject muc h earlier64. But he protests against a living fellow-creature being regarded in the light of a mere subject of experiments of this kind. Rudolf Leuckart confirmed these observations. but the anonymous reviewer of his textbook in th e British and Foreign Medico-Chirurgical Review was scathing in his comments: What does our English reader think of the moral side of this experiment? The reviewer is aware that much may be said of using these and similar opportunities for the promotion of science. During the first few days of March. this will calm anxious souls and serve science at the same time. at autopsy. he began to pass segments of T. The Lancet merely abstracted Küchenmeister's paper including his final point. who indignantly alluded to this experiment at being 'debasing to our common nature'. after recounting these findings and Küchenmeister's assertion that the prisoner could have been treated if pardoned. solium. Leuckart repeated the experiment twice more that year.Taeniasis solium and Cysticercosis he concluded his paper by pleading: 367 that the surely harmless experiment of bladder-worm feeding be allowed to be repeated on criminals under probable death sentence. eleven of them possessing sexuall y mature proglottids and the largest reaching five feet in length. but lacking in a head 53. Aloys Humbert produced a patent infection in himself. Hollenbach also infected himself with C. went on to compare this method . Küchenmeister believed that the sheer numbe r of tapeworms produced ought to convince even the most sceptical that they were derived from the cysticerci that had bee n ingested. the morality of the experiment was questioned. In 1859.. he passed a segment of Taenia five feet long. even though he be a murderer whose hours are numbered. after two and a half months. half of the swallowed cysticerci were found to have developed into T.In the case of the subsequent pardon of a convict. In late 1859. but on both occasions failed to produce a patent infection. he swallowed 13 C. however. Küchenmeister had the opportunity to repeat his origina l experiment. cellulosae. criticism followed inevitably. so that the whole developmental cycle of T.. began to pass proglottids in his faeces. he was treated with kousso and two T.. Again. The prisoner was induced to swallow C. In 1856. notification of this experience was not published until 1856 when it was mentioned by Bertolus in his thesis54. cellulosae on 24 November 1859 an d again on 18 January 1860. He gave four cysticerci to a 30 year old man who. 5 In the same year (1855) that Küchenmeister reported these observations . and made no comment for or against the investigation. totalling 40 bladder worms in all. solium. five months later. The British Medical Journal. He was decap itated on 31 March 1860 and . the tapeworms can be easily expelled. And he ventures to think that few would controvert the conclusion of one of the most eminent physiologists of the day. but on this occasion. In the middle o f December 1854. solium were expelled. Liebenhaar.63 Nevertheless. one month later. solium could be observed. Küchenmeister collaborated with Dr. although one was without a head 65. for he came to be acclaimed as one of the most eminent parasitologists of his day. thing of eyes. solium eggs obtained from proglottids passed by infecte d humans. above all others. Philosopher. The person died 18 days later and autops y revealed twelve heads of T. solium eggs to a pig. solium required not only that mature tapeworms be produced in humans after ingestion of C. A man who'd peep and botanise Upon his mother's grave" These criticisms did not harm Küchenmei ster's ultimate reputation. Brown-Séquard's Journal.for the satisfaction. In 1853. Similar results were then reported by Prof. and it becam e accepted generally that humans were the sole definitive host of T. a prying knave. EXPERIMENTAL PRODUCTION OF CYSTICERCUS CELLULOSAE A complete understanding of the life cycle of T. but they had sought adult worms in the intestines rather than cysticerci in the tissues.368 A History of Human Helminthology of experiment with the ancient way of thinking of the Rationalists. then when it was slaughtered at the abattoirs four and a hal f months later. found a large number of C. The anonymous commentator then went on to cloud irrelevantly and emotively the specific issue in question by referring to: certain rather go-a-head proceedings in this way done by our Yankee medical brethren and recorded in Dr. but all were in vain. established expe rimental scientific methods in the study of helminth infections. who after execution was cut down with a pulse still beating . he gave T. cats. P J van Beneden. Similar results were obtained y et again when Heller gave 22 C. all small and without any segmentation visible50. except that it was not given any eggs. it would appear. of the curiosity of the doctors. cellulosae was the Belgian. solium. pigs. Attempts were then made to infect rabbits. the chest of a criminal. Haubner in collaboration wit h Küchenmeister49. various experimenters had fed eggs to animals. solium. who thought that criminals might fairly be made use of for the purpose of extending medica l knowledge. 6 and then went on to quote Wordsworth: Physician art thou. In view of the economic importance of the subject. cellulosae in the muscles. a s enunciated by Celsus. These gentlemen calmly investigated the movements of a palpitating human heart rapidly ripped from. it had no cysticerci a t autopsy13. and the person who. sheep and cynomolgous monkeys with this parasite. The first person to demonstrate the generation of C. dogs. It will be remembered that from the time of Pallas. Küchen- . This latter course was pursued contemporaneously with the former . Van Beneden controlled the investigation by keeping another pig under the sam e conditions. but that these cy sts should also be generated in pigs following the consumption of T. cellulosae in measly pork.we suppose we may say alive . cellulosae to a patient suffering from phthisis. 00 0 cysticerci per stone (approximately 6. The third hog. In a similar series o f experiments. was massively infected. The obvious conclusion (which. par excellence. Occasionally. they failed to generate C. Three pigs were given T. in civilize d communities. Sometimes. dragged a tapewor m from himself "not without some frightful Apprehensions that the Guts and all were coming out" 107. 24 and 26 J une and on 2 and 13 July 1855. sacrificed on 2 3 August. Haubner and Küchenmeister counted 133 C. thus engendering considerable terror in the patient. furnished with hooks. producing a scolex by a process which was ter med "asexual gemmation". bored their way through the intestinal mucosa an d migrated to the tissues where they lodged and developed into cysticerci . huge segments of worm wer e passed. These observations were confirmed in the following year (1856) by Leuckart who infected successfully a number of pigs and observed them for up to si x months after infection 65. The second pig was slaughtered on 9 August and a thousand cysticerci were disseminated in the viscera. cellulosae although this represented a dead end for the parasite. was that reversed peristalsis might sometimes occur with retrograde movement in the intestines of mature proglottids which in turn then ruptured to release infective eggs. The first animal was killed on 26 July and small cysticerci with incompletely developed heads were found.120. cellulosae in dogs and sheep fed with T. This parasite measured 24 feet in length and numbere d . has neve r been put to the test). at least. were found to be infected with C. has always been the passage of proglottids through the anus. An alternative possibility. naturally. upon the use of an emulsion of cold seeds. was that such infections in humans were acquired b y ingestion of T. like the pig. solium proglottids. solium eggs. solium proglottids on 7. they hatched and the released larvae. cellulosae in 4. Attention then turned to study of the proce sses by which migration and development of larvae occurred in animal intermediate hosts. Tyson records the instance of a 20 year old patient of his. These events were then described in great detail by Yoshino 119. Similar experiences were then reported by Mosle r (1865) and Gerlach (1870). suggested by Leuckart 66. humans.Taeniasis solium and Cysticercosis 369 meister and Haubner had been commissioned by the Royal Saxon Ministry of State to investigate the metamorphosis of cystic worms. The ova could either be ingested in contaminated food or water. or could be transferred directly from the anus to the mouth via fingers. who. Early workers found that when eggs were swallowed by a pig. RECOGNITION OF THE CLINICAL FEATURES TAENIASIS SOLIUM The sign of tapeworm infection. particularly when anthelmintics were taken.4 kg) of pork.5 drachms of meat which was the equivalent of 80. indigestion. of course. Either two or three tapeworms grew and th e number of gravid proglottids passed were 334 in the first month. Dr.370 A History of Human Helminthology 507 proglottids. 174 in th e sixth and 126 in the twelfth month of patent infection. a healthy woman who was treated with extract of male fern and castor oil passed four portions o f tapeworm (species not identified) into a bucket. impaired vision. scientifi c analysis. many of them being considered "sympathetic phenomena" and so-called "proof" of the aetiological relationship bein g provided by their cessation after removal of the offending parasite. a n itchy nose or anus. Very often. Küchenmeister was more circumspect than this. The stronger an individual is. palpitations. the less does he complain of his symptoms when he suffers from tapeworm. anxiousness. salivation. and were not subjected to rigorous. No heads were recovered. solium. Wagler. all the portions belonged to the same strobile 70.2 metres) and in places the proglottids had a breadth of 1" (2. The fact that humans usually suffer infection with only a singl e tapeworm was often interpreted as evidence of immunity to reinfection. The life span of T. In more recent times. according to Davaine (1860). an insatiable appetite and convulsions 29. the total length attained 79'4" (24. tapeworms might cause general indisposition. These were anecdotal accounts. In order to determine how many proglottids are produced and passed by a tapeworm. a multitude of symptoms were ascribed to tapeworm infection. colic . perhaps the record being the patient who was reported as having 25 mature tapeworms 86.5 cm). cellulosae then observed himself for the next two years. and diabetes 57. but is was realized that this could also indicate non-immunological resistance which . multiple infections are possible. Otherwise he was healthy and had great strength. noting: All these symptoms are very deceptive if we should ascribe them to the presence of the tapeworm. they do not disappear when the worm is expelled. 62 Time has supported Küchenmeister's cautions.122. although whether this was all from one worm is questionable 18. The majority of patients were asymptomatic or had vague . syncope. Yoshino (1934) infected hims elf with 3 C. this approximates to 1-5 proglottids per worm per day 121. Borrichius is said to have seen a patient who voided more than 800 feet of tapeworm during the co urse of a year. anorexia.112 Wagler's observation that the young scholar was otherwise healthy was the usual finding. insanity117. emaciation. noises in the ears. I have seen anxiety and unpleasant sensation from music in several cases of taeniasis. While many patients are infected wi th only one T. giddiness. The total length of worm passed could sometimes b e extraordinary. a proof that the latter is not their first cause. but these tapeworms probably live for many years. indefinite abdominal discomfort. Nevertheless. solium is uncertain. To these might be added chorea 40. Goeze (1782) quotes the unusual case of a patient of his friend. Thus. but as far as the autho r could ascertain. When laid out and measured. weariness. he was a young scholar who felt little distress except when he heard music: Then he had to run away or of fear had to ask that one would stop the music. Some persons had smaller o r larger numbers of subcutaneous nodules. they can be felt singly. scalp.. Thus. One cyst is present in the left eye. patients were asymptomatic. He gives the appearance of being a powerful man. They are found in the aponeuroses of the abdomen. When single. Enlargement is due to the presence of the cysticerci and to the concomitant myositis. attended the Scottis h Highland Games and took second place in the long jump 35. and on contraction the muscles present a nodular appearance. von Graefe (1866) found intestinal tapeworms in five of 8 0 patients with ocular cysticercosis 46. as instanced by the incidental discoveries by Wharton and Werner of th e organisms in previously healthy individuals.. MacArthur (1935) hypothesized that th e biological objective of cysticerci while in the tissues of the intermediate host is to remain quiescent and he likened them to: "thieves who have entered some premises where they stay hidden so long as concealment is helpful to thei r purpose"73 and suggested that death of the parasite may have liberated toxins . however. but two outstanding features were the chain of nodules visible on the forehead and the greatly enlarged. One of the more dramatic examples of a patient with disseminated cysticercosis was described thus: He was pale and the face appeared puffy. By the time Cobbold wrote his textbook on helminthology in 1864. In size.88 Such infections frequently left no serious musculo-skeletal sequelae. Definitive studies in which the recurrence of infection in a treated subpopulation in a n endemic area is assessed are still awaited. Occasionally the two conditions occurred together in the sam e patient. these appeared to be associated with death of the worms.but the muscle power is in fact very feeble. they are ovoid.. as evidenced by the man with hundreds of calcified cysts in his muscles. They are movable and not at all adherent to the skin. it wa s well-recognized that cerebral cysticer cosis might cause convulsions and mental disturbances as well as various cranial nerve and long tract signs 26.. In explanation of this. in groups and in chains. beneath the left eye.... Nearly all the muscles are enlarged.72. especially those of the shoulder girdle. They have never been painful. apparently well developed and powerful muscles. interest in this subject was re-awakened when a large number of Britis h soldiers returning from various outposts of Empire with "idiopathic epilepsy" were found to be suffering from cerebral cysticercosis 71. who after three days in hospital following an epileptic fit.are found in the subcutaneous tissues of the forehead. or spherical according to the amount of pressure exerted by the surrounding tissues. They occur singly or in groups of two or three of varying size. they range downwards from half an inch in longest diameter. An unexpected feature of this study was that parasite s were often present for many years before the onset of cerebral symptoms. In the muscles. CYSTICERCOSIS Cysticercosis in humans was recognized much less frequently than was taeniasis solium. in the neck and in the tissues of the cheek.Taeniasis solium and Cysticercosis 371 was dependent upon the continuing presen ce of an adult tapeworm 28. elbow-joints.. In 1934. flattened ovoid. thighs and legs. .The nodules. In many cases.. At the same time. it was found that this method also enhanced the ability to diagnose tapeworm infections. solium and T. see chapter 14). it became obvious that the outlook for patients with cysticercosi s was dependent upon both the number of cysticerc i and their location in the host. mediocanellata. but identification of the species of worm was not possible from these specimens for many years. After Küchenmeister described in 1852 the appearances of the reproductive organs. solium infections. subsequent exper ience indicated that this technique did not permit differentiation of T. emphasized the value of faeca l examination29. those situated in the ventricles of the brain o r subarachnoid spaces could grow much larger and endanger life. saginata infections. Similarly. Despite the manifest advantages of a reliable immunodiagnostic assay for cysticercosis. He was followed soon afterwards by Davaine who. although diagnosis was helped when eosinophils were found in t he cerebrospinal fluid 113. identification of the proglottids became possible on a routine basis. The only certain method of diagnosis was by specific identification of the parasite following surgical removal of a cyst. saginata (which he called T. solium and T. With the introduction of the perianal swab tech nique for the diagnosis of enterobiasis (see chapter 17). Despite occasional claims to the contrary. but this was ofte n less feasible. Whereas parasites in most tissues were usually of minor significance and were generally limited to less than one centimetre in size by the host inflammatory and fibrotic reaction. On the other hand. At about the same period. in his textbook. Alternatively. saginata 87. repeate d . the diagnosis of cysticercosis was an altogether different proposition.372 A History of Human Helminthology which increased the irritation which they caused. a cysticercus in a strategic organ such as the eye could seriously impair vision. advances i n ophthalmology and neurosurgery and the recent advent of effective anthelm intics have improved the outlook considerably for many of these persons. particularly those due to T. DEVELOPMENT OF DIAGNOSTIC METHODS The diagnosis of tapeworm infection was obvious when a patient passed proglottids. it was also found that a diagnosis of tapeworm infection could be made by demonstration of taeniid eggs in the faeces. Whereas little could be done for such patients in the past. The first person to describe such eggs (which he took to be indicative of a new species of tapeworm) in faeces was Ransom in 1856 89. a specific diagnosis could also be made afte r treatment of a patient and recovery of the tapeworm head. The recognition that humans might develop c ysticercosis by ingestion of eggs after contamination of their fingers with faeces or by peri-anal scratching lent urgency to the diagnosis and effective treatment of T. parti cularly the number of lateral branches on the gravid uterus in T. This was particularl y difficult in patients with cerebral cysticercosis. maintai ned the premier place in the array of antitapeworm anthelmintics until the middle of the present century 23. Anecdotal clinical experiences over centuries hav e provided fairly convincing evidence of the efficacies of many of these drugs . otherwise called filix mas or extract of male fern. Küchenmeiste r attempted to produce some order out of the chaos by a series of in vitro experiments in which he mixed Taenia ova in egg white with various com pounds and determined the time that the ova took to die 62. which is prepared from rhizomes of the plant now known as Dryoptera filix mas. Serodiagnosis of cysticercosis began with the studies in animals of Weinberg 114 and with the demonstration by Fairley that complement fixing antibodies were present in the serum of only two thi rds of selected patients 36. we must say that the therapeutics of the tapeworm is extremely defective. dry rhizomes in ether for 48 hours. These plants are widespread in the norther n hemisphere. which w as purchased for 18. These assays have not yet found a routine place in the diagnosis of cysticercosis 38. THE SEARCH FOR EFFECTIVE TREATMENT Remedies effective against tapeworms have been sought and their virtue s expounded from the earliest time s23.000 francs in 1776 . dates from the time of early Greek medicine. So many agents had been declared to have anthelmintic properties. An extract was obtained by soaking th e powdered. Filix mas. Switzerland.62 Yet this was not entirely fair. Küchenmeister was induced to declare: if the multitude of remedies recommended for any disease is an evidence of their want of power against it. This elixir. New radiological techniques such as CT scanning and magnetic resonance imaging ma y facilitate greatly the diagnosis. freed from roots and dead parts.Taeniasis solium and Cysticercosis 373 attempts to develop such tests have not led to significant improvements . The rhizomes were collected in the autumn. or its principal anthelmintic constituent. filicic acid or filicin. Radiology has had more to offer. It is only in the last 100 years that various putative anthelmintics have been submitted to carefu l clinical trial and rigorous scientific analysis. They were often given concurrently with powerful purgatives which increased peristalsis and assisted in evacuation of the tapeworm. in fact. This drug. for many of these preparations did possess some antitapeworm activity. that in the middle of the nineteenth century. then the ethereal phase wa s filtered and concentrated. was the major component of the famous but secret tapeworm remedy of Madame Nouffer in Morat. then dried carefully. Perhaps the best known and most commonly used anthelmintic in the treatment of tapeworm infection over the centuries has been oleoresin of Aspidium. particularly in patients with cerebra l cysticercosis. Calcification of dead cysticerci appears to have been demonstrated radiologically first by Roth in 1926 94. Physiologus (Prof. Bennet). A less toxic drug is kamala which had been known since the late Middl e Ages. Nor I. a plant which is widespread in the Orient 23. Bennet). No. Medicus (Prof. Bennet). Punica granatum. male fern and kousso were the most commonly used drugs. finding the head wa s not a simple task. and pyret hrin powder prepared from the flowers of C. cinerariifolium has been used recently as an anthelmintic 23. Another anthelmintic which caught the imagination of European doctors during the last century was kousso. Did you ever know any one who has found one? Chirugus (Prof. was recognized during the Middle Empire of ancient Egypt. It is found in the glands and hairs covering the fruits of Mallotus philippinensis. a plant which is common in Ethiopia. but I doubt the authority. cultivated in Asia. I have been looking for a tapeworm head all my life but have not yet found one. and some practitioners were not convinced of the necessity. Physiologus (Prof. although kamala had its advocates and turpentine was popular7. taenia? Medicus (Prof. I knew Rudolphi. So it is pretended.80. The anthelmintic activity of the pomegranate. this has been shown in recent decades to be due to its alkaloid. Yes. arecoline. prepared from the blood red flowers of Hagenia abyssinica (= Brayera anthelmintica). while preparations based upon the combination of metallic tin with oxide and salts are more recent origin23. By the middle of the nineteenth century. Although this last drug was often effective. 56 The complexity of the various therapeutic regimens is illustrated by th e method recommended by Magath and Brown in 1927 in a paper entitled : . 56 The more enlightened practitioners realized that proof of the effectiveness of a drug was either recovery of the head of the parasite or failure to pas s proglottids over the next several months. Did you find the heads of the creatures . Jenner (1856 ) believed that: its horribly nauseous flavour and unpleasant effects on the head and occasionally on the kidneys (made it) a remedy which should only be used as a last resort. Christison). you can scarcely say the patients were cured. pelleteriene23.56. Editor (Dr. Betel nut.i. its active principle. Nor I. Christison).e. Areca catechu. has been used in more recent times. Syme). Nevertheless. But if you say you did not find the head in your cases. The firs t recorded use of the drug in that country was around 1550 AD and it became an important article of trade 84. That is no easy matter. has been employed in th e treatment of tapeworm infections in C hina for 1400 years 69. the seed of the palm. Pumpkins seeds (especially Cucurbita pepo) ground into a paste is another traditional remedy which has been shown i n recent years to have considerable antitapeworm activity 77.19. anthelmintic activity has been claimed for Chrysanthemum for many centuries. as evidenced by the following conversation among various learned professors of Edinburgh University in 1852: Physiologus (Prof. Robertson).374 A History of Human Helminthology by the French government. Likewise. Metallic tin has been given for tapeworm infections for some centuries. although this view has been dispute d recently91. but sinc e administration of this drug may precipitate severe side-effects. This was followed after another two hours by 30 g of magnesium sulphate. Gönnert and Schraufstätter screened a g reat number of salicylamide derivatives and reported in 1960 that this particular compound was extremely activ e against Hymenolepis diminuta in rats45. in addition. . and. a large enema of soapsuds was given. At 6.00 a. including thymol 3. solium (adult worms). 79 hexylresorcinol 76. the patient was prohibite d from taking either the midday or evening meal. praziquantel. mepacrine . A number of synthetic compounds with antitapeworm activity have bee n introduced in the twentieth century. Niclosamide caused lysis of tapeworms in the intestines. with cure rates ranging between 80% and 100% 27. Five years later. carbon tetrachloride 22.33. concurrent use of corticosteroids may be needed to suppress the inflammatory reaction 47. and without having had any breakfast. niclosamide . together with symptomatic treatment of complications such as epilepsy. 55 118 97 dichlorophen . then finally. it was noted to b e active against C. chloroquine. many physicians during the last few years of their popularity preferred to administer them through a d uodenal tube. T. On the day preceding specific treatment.m.92. In 1972. betanaphthol.00 p. After the bowels had moved. solium infections.60. a further 30 ml were taken. was effective against Hymenolepis species21. quinine102. One hour later.m. latum. 15-30 g of magnesium sulphate were admin istered then this was repeated next morning at 6. including cysticerci in the brain.. World-wide clinical trials followed and showed that the drug was highly active against practically all the tapeworm s infecting man. so concurrent administration of a laxative was deemed advisable because of the theoretical risk of causing cysticercosis in T. was found to have unusually broad anthelmintic activity. The treatment of cysticercosis has been surgical with removal or parasite s whenever possible. It is possible that praziquantel may revolutionize the management of cysticercosis in many patie nts and obviate the need for surgical intervention. an heterocyclic pyrazino-isoquinoline derivative. after Schneider (1924) had shown that small doses could be used just as effectively but with less sideeffects when this technique was adopted 98. two hours after this. . it wa s reported that this drug had cure rates of nearly 100% in patients infected with T. saginata and D. paromomycin and mebendazole 81 Of these. mepacrine secured the most favoured place for a while. bithionol . Since the margin between therapeutic and toxic doses of these drugs wa s slight. the patient was given 30 ml of an emulsion of oleoresin of aspidium together with powdered acacia in 60 ml of water.74. Furthermore. but was permitted black coffee or water freely.Taeniasis solium and Cysticercosis 375 "Standardized method of treating tapeworm infections in Man to recover th e head". but it was the n superseded by the introduction of the salicylamide derivative. cellulosae. Asia and Central and South America. Küchenmeister meant the necessity for the thorough cooking of all por k. salted or smoked pork was not necessarily safe 15 but that . The value of proper cooking of pork was emphasized several years later when th e transmission of Trichinella spiralis in this medium was also demonstrated. solium. similar frequencies are still seen in many countries of Africa. Further researche s indicated that pickled. saginata (see chapter 14). By public instruction. Further studies on his part revealed that these cysts could remain viable for up to a week after slaughtering a pig 64. a dead end for the parasite i n most human societies. The temperatures necessary to kill cysticerci were investigated by Perroncito in a series of experiments with T. were now well-understood. cellulosae and the production of these cysts in pigs by feeding them with gravid proglottids obtained from infected humans clarified th e epidemiology of taeniasis solium. This high frequency of infection was explained by the demonstration that enormous numbers of eggs were released by each proglottid. It became obvious that this infection was a zoonosis and that humans were not only the definitive host of the adul t tapeworms. THE EVOLUTION OF PREVENTIVE AND CONTROL MEASURES Comprehension of the life cycle of T. the reasons for the previously well-recognized paucity o f infection in certain religious groups such as Muslims and Jews.376 A History of Human Helminthology UNDERSTANDING THE EPIDEMIOLOGY The elucidation of the life cycle of T. solium by experimental infection o f humans with C.000 eggs or more into the environment each day. In his paper of 1855 detailing th e experimental infection of a human with T. who wer e forbidden to eat pork. of course. Thus. for example. Although the insti tution of control measures has reduced greatly the prevalence of infection in Europe. Küchenmeister was quick to point out the implications for a population that was in the habit of eating raw pork and recommended that the best method of preventing infection with adult tapeworms would be by "public instruction and warning to be careful wit h infected pork"63.000 eggs whil e creeping about121. Further studies confirmed that humans alone were the definitive host of the worm and pigs were the only significant vector o f infection. Thus. solium provided a rational basis for the institution of effective control measures. although this was. approximately 2% of post-mortem examination s of humans conducted in Berlin revealed cysticercosis. but could also be a potential intermediate host with the acquisition of cysticercosis. each infected person might release 100.5% and 20% in thes e regions. Yoshino calculated that each proglottid discharged about 40. Attention then turned to defining the prevalence of infection in pigs and i n humans in various parts of the world110. During the first half of the last century. wit h cysticercosis in slaughtered pigs ranging betgween 0. In this respect. personal hygiene. Didot. Viljoe n (1937) recorded the instance of the South African farmer and his househol d who preferred to use the rear of a hedge close to the homestead rather than a stinking. graece et latine. par M. Lugduni. De la génération de vers dans le corps de l'homme.Taeniasis solium and Cysticercosis 377 freezing at -10 oC for a week110 or at -20oC for at least 12 hours was an effective control measure 15. 1912 4. pp 468. 1549 3. however. taeniasis and cysticercosis are both now kept at bay by a combination of treatment with effective anthelmintics. 1984 . The seven books of Paulus Aegineta. De re medica. translated by H Rhodes and A Bell. Recently. ANDRY de BOISREGARD N. five volumes. G et M Beringer. British Medical Journal i: 46. International Journal for Parasitology 14: 539-540. . be cleaned immediately by pigs trained to come at a whistle. The Sydenham Society. ARISTOTLE. les deux premières. Georges Baglivi. ANONYMOUS. By these means. The treatment of tapeworm. Similarly. and storage of pork in refrigerators. Thymol for Taenia saginata. vegetable s grown in gardens fertilized with human faeces were especially dangerous and needed to be avoided.. fly-infested privy. 1861 7. 1857 6. 1844-1847 2. A mere recitation of th e facts was often insufficient to attain these ends. An account of the breeding o f worms in human bodies etc. AEGINETA P. Lancet i: 442. 1848-1874 9. In. Journal of the American Medical Association 59: 197. F Dübner. solium shaken when their scrupulously-styed pigs developed cysticercosis. it was hoped that the incidence o f human cysticercosis would be reduc ed and that the economic wastage resulting from the condemnation of pork would be curtailed. The terminology of parasitology: the need for uniformity. In developed countries.. Parisiis. De lumbrico lato. it became apparent that good sanitation. was essential for the prevention of both porcine and human cysticercosis. AETIUS ANTIOCHENUS.. Medica Graeci contractae ex veteribu s medicinae tetrabiblos etc. three farmers of high repute had the ir faith in the life cycle of T.par M. cum indice nominum et rerum absolutissimo. Nicolas Hartsoeker et l'autre . Finally. translated by F Adams. ANONYMOUS. ANONYMOUS. the effectiveness of prompt diagnosis and treatment of T. particularly with respect to disposal of human wastes. efficient disposal of human wastes. 1700. and intensive health education was often required to achieve a change of habits. This area could. Avec trois s lettres sur les sujets des vers. Thus. rigid inspection and disposal of infecte d meat. ARME C.. it has also been shown that infected carcasses can be sterilized by gamma irradiation without affecting the quality of the meat 109. subsequent detectio n revealed that some black members of the staff were in the habit of easin g themselves in the sty and that one of them had tapeworm infection 110. 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Recherches des anticorps spécifiques dans la distomatose etla cysticercose. Rumlerus J.1300 AD 112. Lipsiae. 1913 114. VERSIER H. YOSHINO K. YOSHIMURA H. In Japanese.) Taiwan Igakkai Zasshi 33: 183-194. Edita e t animadversionibus atque tabulis a aeneis aucta JL Fischer. WOOD W. Original edition c. 1585. WHARTON T. VELSCHIUS GH. Part II. 1909 115. YOSHINO K. Part III. Taiwa n Igakkai Zasshi 32: 1717-1736. with special reference to South African conditions. VILLANOVANI A. with English summary 121. YOSHINO K. Augustae Vindelicorum. In Japanese 123. VILJOEN NF. solium. cellulosae in the muscles of a pig fed with T. one being five feet in length 1926 Roth demonstrated calcified cysticerci by radiography 1934 Fairley showed that antibodies were present in the sera of patients with cysticercosis 1960 Niclosamide was introduced for the treatment of intestinal taeniasis 1977 Praziquantel was introduced for the treatment of intestinal taeniasis 1980 Praziquantel was shown to be effective in cysticercosis __________________________________________________________________ . cellulosae in pork to a condemned murderer 4 and 2. including extract of male fern (filix mas). Landmarks in taeniasis solium and cysticercosis ___________________________________________________________________ BC Tapeworms in humans and cysticerci in animals were known but their true nature was not appreciated. cellulosae in pork to a condemned murderer and recovered small tapeworms several days later 1855 Humbert infected himself with C. solium three months later 1856 Ransom described the diagnosis of intestinal taeniasis by finding eggs on microscopical examination of the faeces 1860 Küchenmeister fed C.1550 Kamala and kousso were introduced as antitapeworm agents 1558 Rumler probably described cysticerci in a human 1683 Tyson discovered the head of a tapeworm 1688 Hartmann discovered the verminous nature of C. Multiple remedies. then recovered a large number of adult T. cellulosae in pigs 1854 van Beneden reported that he had generated C.5 months prior to execution.Taeniasis solium and Cysticercosis 383 Table 13. cellulosae in pigs 1784 Goeze pointed out the similarities between the heads of tapeworms found in the human intestinal tract and the invaginated heads in C.1. cellulosae then began passing segments of T. were described for intestinal taeniasis c. solium ova 1855 Küchenmeister fed C. . even when a head was not available for examination. saginata. especially the muscles. D. the head evaginates in the small intestine and develops into an adult tapeworm which produces proglottids after approximately two months Definitive host: humans Intermediate host: cattle Major clinical features: abdominal discomfort. Eggs and gravid proglottids are passed in the faeces. amongst many others. however. Distinction between D. usually about 5 metres in length.Chapter 14 Taenia saginata and TAENIASIS SAGINATA SYNOPSIS Common name: tapeworm Major synonym: T. the eggs hatch in the small intestine and each released larva (oncosphere) penetrates the mucosa and passes via the bloodstream to the tissues. because the shape of the proglottids and the position of the genital pore were quit e different. were hopelessly confuse d and intermingled for many centuries. subcutaneous tissues and central nervous system. but conceptions about the three species of large tapeworms that commonly infect man. As discussed in Chapter 15. latum began to be recognized as a separate entity in the seventeenth century. saginata and Diphyllobothrium latum . T. of T. live in the small intestine with the head attached to the mucosa. solium. leaving the other two species lumped together under the name. for the distinguishing fe atures in the proglottids are much more subtle and their classification required a knowledge of their interna l anatomy. It required the discovery o f tapeworm heads before definite distinction between these two species wa s 385 . latum and the species of Taenia was relatively easy. particularly the branches of the uterus. It was another matter with the worms we now know as T. solium and T. saginata) in the faeces Treatment: niclosamide. Taenia solium. mediocanellata Distribution: worldwide Life cycle: The adult tapeworms. praziquantel DIFFERENTIATION OF THE SPECIES FROM TAENIA SOLIUM Tapeworms have been known for generations (see chapter 13). these usually reach 10 mm in size and contain an invaginated head. When ingested by cattle. When a cysticercus in insufficiently cooked beef is ingested by a human. spontaneous passage of proglottids Diagnosis: finding of eggs (any Taenia) or proglottids (T. where it vesiculates to form a bladderworm (Cysticercus bovis). 386 A History of Human Helminthology achieved. Andry not only provided illustrations of the proglottids. recognizing both the morphological differences and th e variations in the geographical distribution of the two forms. saginata indicated that one parasite was large and fat . solium and T. he was in fact describing T. in 1782. stout. some right. the segments are much narrower and almost pushed one on top of the other and thereby give a considerable thickness. solium (which he called T. with thick. a cestode which was none other than T. The scolex had no hooks and there is no doubt that this worm was T. with the head of T. the first is well known . solium 39. Johannes Goeze. which is hardly ever the same. Linnaeus. saginata. Remarkably though. Peter Pallas was also confused by this variability. plana. thick and fat 31. which under all circumstances remains the same and is found in my part of the country more frequently than the former. saginata 2. but he was completely unaware of the existence of two species o f Taenia.In the next ell of this specimen. saginata and the body of D. but are much thicker. however. pellucida. under the designation T. seven without heads and two complete examples. although he did note that the worm had some variations in its appearance 27. The most mature lower segments are not as long as in the flat. transparent variety. saginata under the name of T. latum. separated the human taeniid tapeworms into two categories: I know and possess two species of intestinal tapeworm. Nicolas Andry de Boisregard described. His name of Taenia cucurbitina. 12 Goeze was intrigued by variations in position of the marginal openings for he noted that "The order in the position of the marginal openings. solium or Taenia sans épine (Taenia without thorns). 170 years were to pass after Tyson's discovery of the head of a tapeworm (see chapter 13). Goeze called these worms T. describing an d figuring T. Again. saginata. As discussed in chapter 15. grandis. pellucida reflected the flat and transparent nature of the other tapeworm.. plana. cucurbitina. saginata. solium. still remains very puzzling and yet it cannot be withou t .13 metres and a Flemish ell is 68 cm] in length. described what was in fact a T. I call it Taenia cucurbitina. Although he did not realize it. Some have the thickness of half a line [1mm] and are all marked with little lines lengthwise on the surface. the marginal openings are set in each segment. saginata. one on each segment. The second seems to be a variety of the first. gave drawings of the head of a tapeworm obtained from a human.12 Like Pallas. he did.long. some left. and at other times. Vallisneri in 1714 again made the same mistake. but also.. while the Taenia cucurbitina. Goeze possessed nine specimens of T. before general agreement on the two species was obtained. Charles Bonnet then drew a hybrid tapeworm in 1750. in his Systema Naturae (1758). respectively. In 1700. saginata as the typical form of the Taenia infecting Man. for the first time. under the name T.. In a section of worm more than one ell [an English ell is 1. grandis. cucurbitina. thin and narrow. correct this error in 1777. He wrote that: It is truly amazing to compare the pieces of this flattened tapeworm with others. fattened segments which I shall call Taenia cucurbitina. and to which he ascribed a crown of thorns) was sometimes delicate. He wrote that T. he preferred the name T. saginata continued to be confounded with T. a physician in Berlin. solium). grandis. solium. solium from T. ascarislike. Batsch expresse d similar views to Goeze. these judicious observations largely passed unnoticed or were ignored. by contrast . cucurbitina and distinguished two constant varieties within this species. Several years later. saginata. T. along with . saginata that he possessed.12 Goeze then went on to contrast the appearance of the flat. Bloch proposed in this essay a classif ication of tapeworms in which. as mere observation shows. saginata. Indeed. these were recognizable by the features mentioned b y Goeze. the presence or absence of hooks on the head was used as a specific character. pellucida which were complete with head. transparent variety. solium 7. plana. Goeze had several specimens of Taenia cucurbitina. Taenia cucurbitina. he did not stress (and perhaps was not aware of) the value of this feature i n distinguishing T.Taeniasis saginata 387 purpose"12. it is flatter. Rudolphi saw onl y specimens of Taenia with hooks. in the latter. Batsch was also aware of regional variations in the relativ e frequencies of the forms of tapeworms 3. for the first time. At the four corners of the head there are four suckers and a superior rostellum which can be seen through the microscope. are inborn in animals or enter from outside". In addition. or was simply considered as a variety of the latter. In the first. then he described definitively the head of the tapeworm now called T. M. Bloch. encountered only Taenia without hooks. Although he divided the genus Taenia into the "inarmatae" containing 1 6 species and the "armatae" with four species. plana.e. pellucida (i. the accompanying figures indicate clearly the four suckers and the crown with two rows of hooks. grandis. the latter species not having a crown of hooks. merely writing: In the first specimen the head is not flat and ribbonlike but round.12 In addition. solium was unequivocal. T. however. saginata and T. As with Pallas. solium: The head of the worm is like a small box and not round. T. the suckers and the hooks with the naked eye. grandis. Although Goeze's description of the head of T. I am only adding that the head end of both of these specimens is completely different from the head end of the notched. Amongst other things. saginata. while Bremser in Vienna. Thus in Berlin. as in the cat's tapeworm. segmented tapeworm from the cat. The title of this essay was "Concerning the seeds of intestinal worms: whether tapeworms etc. He did not dwell at length on the appearances of the two heads of the Taenia cucurbitina. and the segments only start after a very narrow neck. Just before Goeze published his findings. Nevertheless. he did not use this feature t o differentiate between the human tapeworms. He noted that the dendritic ramifications of the uterus were far more defined and visible in this form of tapeworm than in Taenia cucurbitina. contributed a discourse which won the gold medal given by th e Academy of Science at Copenhagen for its prize essay set in 1780. however. as well as upon the ramifications of the uterine branches that he noted. after first proving that it was not simply an immature form of Taenia cucurbitina. Bremser 8 believed. one cannot see. but his views were still not heeded. This name was then adopted generally. mediocanellata. only armed Taenia occurred40. Again. whereas the other species. and had consulted it more carefully. solium there was another large-jointed species to be distinguished in man. In 1852. solium whereas the other species had 15-20 such branches. there were 9-15 lateral uterine branches in the proglottids of T. he gave Küchenmeister little credit: In 1852. Küchenmeister gave the name T. name d them Bothriocephalus tropicus. just as an ageing man loses his hair. In 1830. but was rather only a confirmation and extension of observations which would have long since been fully settled if the observers had a more rich and complete material to work upon. founded on an erroneous anatomical idea. but the problem was solved when Leuckart in 1867 pointed out that Goeze had earlier used th e designation "saginata" to describ e this species and that the correct name should therefore be T. Thus . not only by their genera l appearances.20. mediocanellata. This created a dilemma since such usage flew in the face of precedent.if Küchenmeister had been better acquainted with the literature of helminthology. saginata and T. solium was armed with hooks. but particularly by the structures of their heads and thei r reproductive systems. the specific epithet denoting a main transverse channel running through the region between th e four sucking discs 19. Similarly in Java. Further examples of regional variations in the type of tapeworm present were described..26. although first Leuckart then Blanchard 6 considered that it would be more in keeping with . only unarmed taeniae were present. inerme or T. solium was not generally recognized until Küchenmeister's publication. but some of the purists objected to thi s nomenclature on the suspect ground that t he term "mediocanellata" was derived from a combination of Greek and Latin roots. Friedrich Küchenmeister declared that there were definitely tw o distinct species of Taenia. Some authors consequentl y preferred the term T.388 A History of Human Helminthology FS Leuckart and Mehlis. dentata 29. Not only was Küchenmeister's designation. Küchenmeister again advanced the opinion that besides T. clearly distinguishable. Schmidtmuller examined 148 taeniae in the space of 15 years. he would have learned that his discovery was not as new as he supposed.. but was accepted thereafter. saginata 25. He observed that the head of T. while in the region in the Necker basin . T. The situation became so confused that neither Dujardin (1845) nor Diesing (1849-1851) in their major textbooks admitted two distinct species of Taenia infecting humans.26 This comment was typical of Leuckart's penchant for unfair criticism o f Küchenmeister. The fact is that the distinction between T. inermis to describe T. Wawruch noted that in the parts of Wurtemberg situated in the Danube basin. and finding them all to be unarmed. When Leuckart reviewed this matter a few years later. that all young taeniae had hooks and lost them with advancing age. which was also larger and fatter. To this latter species. saginata.. Nicolai agai n drew attention to the presence of hooks in on e form of tapeworm and named the parasite T. was always bare of hooks. A. particularly those in St. saginata 41. Huber pu t forward the hypothesis that cysticerci would be found in the tissues of cattle 14. Judas probably saw cysticerci of T. led Rudolf Leuckart to investigate the effects of feeding such eggs to cattle. In 1860. but thought this unlikely since thi s species is generally found in the liver and mesentery whereas C. T. some have considered that there are number of suc h species32. although he did not recognise them as such 16. Petersburg (no w Leningrad. therefore. Furthermore. Leuckart fed .Taeniasis saginata 389 the rules of zoological nomenclature to accord the name T. that such a course was impractical and woul d augment the already consider able confusion which surrounded the terminology of tapeworms. that specimens of Taenia submitted to him from South Africa were T. BOVIS The successful demonstration in the 1850's of the complete life cycle o f T. and that raw. Algeria in 1854. moreover. but acquired infections with T. tenuicollis. together with the failure o f several previous attempts to infect pigs and sheep with T. while most investigators believe there to be only one species of beef tapeworm infecting humans. The difficulty was to know wh ich animal was the intermediate host containing cysticerci. saginata. Leuckart knew. solium. bovis may be found in the lungs of cattle. Finally. Army surgeon Knox had witnessed a tapeworm epidemic among soldiers who had eate n "overdriven and unsound" oxen during the first Kaffir War in South Africa 18. These pointers. solium naturally suggested that a similar process might occur wit h T. On 13 November 1861. who were proscribed from eating pork. saginata eggs and the observations of Knox. pellucida Goeze. travellers to various parts of the globe reported that T. It was also realised that European Jews. were not afflicted with T. Blanchard6 has canvassed the possibility tha t Judas had in fact found C. Physicians had noticed that sickly children. not infrequently contracted infection with T. USSR). however. The clue was to come from clinical and epidemiological observations. Discussion has continued until the present day with som e taxonomists believing that the unnamed tapeworm of man acquired by th e consumption of beef should be called Taeniarhynchus saginata whereas other authorities believe Taenia saginata to be the correct designation. The most notorious of these was Abyssinia (Ethiopia) where almost everyone was infected and where the inhabitants ate mostly beef. saginata. solium to the unarmed tapeworm and call the tapeworm with hooks. saginata in the lungs of cattle in the abattoirs at Orleansville. saginata infections were more common in cert ain countries. ELUCIDATION OF THE MODE OF TRANSMISSION EXPERIMENTAL PRODUCTION OF C. saginata. They conceded. by preference. who had been ordered to eat raw beef in order to strengthen them. saginata about four feet long to a four week old calf.. Leuckart's findings were confirmed twice in 1863 by Mosler 28. saginata. all the muscles and some of the visceral organs as well as the lymphatics were permeated with: cysts which were 1. it was c lear that cattle were the intermediate host of T. Th e cysticercus was designated Cysticercus ex Taenia mediocanellatae by Davaine then as C. solium with respect to size. was already provided with completely developed suckers. At post-mortem examination. saginata and. saginata. and demonstrated that rabbits were likewise inhospitable hosts. Seven weeks after infection. Gerlach (1870). a tight circle of small rudiments. furthermore. They had a whitish appearance as though filled with a chalky or caseous mass.390 A History of Human Helminthology a mature segment of T. no suckers could be found. then by Roll (1865). In contrast to the scolex of C. Perhaps the y wanted a ready demonstration of the almost incredible phenomenon of th e migration of worms and the alternation of generations. and this provided a convenient excuse and a workable system. between the suckers. that he had shown that infection with this parasite was acquired by humans from cattle and possibly othe r ruminants22.. and that this might partly account for it having escaped the attention of helminthologists up to that time. cellulosae: this head cone was without a bend and in spite of its small size (hardly 1 mm). 24 Leuckart believed that the larval stage of T. Masse and Pourquier (1876). bovis by Cobbold 10. Jolicoeur ( 1873). Saint-Cyr (1873). by Cobbold and Simonds in 1864 and again in 1865 38. He concluded that by these experiments he had established beyond any doubt the specifi c nature of T. there was on the bottom of the invagination. The animal became quite sick during the third week after infection. In any event. Various investigators confirmed the earl y observations that pigs and sheep were insusceptible to this species of tape worm. On cutting into this cyst.7 mm in diameter. then reinfected the animal one week later with smaller pieces of the sam e tapeworm. also in spite of the small size of the vesicle (3-4 mm). as I had never observed in any young cysts of the Cysticercus cellulosae in a similar way.24 Leuckart then repeated the experiment and infected another calf with 25-3 0 proglottids of T.At this stage of development. Perhaps they wanted to prove their mastery over these worms.5-3 mm wide and 2-4 mm in length.. saginata may lag behind that of T. The inner parts of the head cone showed little enlargement of the end. a biopsy was taken from the sternomastoid muscles and about a dozen cysticerci were obtained. but then recovered completely. Zurn (1872). Inside the exudative layer. the latter name has stuck. Perhaps it simply gave them a feeling of achievement and satisfaction.23.4-1. Instead of the protruding hooks. this protruded and proved on closer examination to be a young cysticercus. Perroncito (1877) and others. One wonders why so many investigators felt it necessary to confirm these findings. they contained a light. and that humans were likely to acquire infection with this . The animal appeared well but then died suddenly on 8 December. which was surrounded by a firm connective tissue membrane. clear vesicle of 0. and in the region of the smaller cysticerci it was a simple conical shape. a British medical officer stationed with the Royal Artillery a t Jullundur. a control subject ingested an uncooked C. 391 EXPERIMENTAL GENERATION OF ADULT T. . no-one went to Küchenmeister's lengths and infected a criminal destined to be executed. They all declared that they were free of taenia. he began to pass proglottids. 2nd . mediocanellata. In that investigation. there seemed little doubt that humans acquired T. bovis on 4 March 1877. India. except that infection was acquired by ingestion of contaminated beef instead of pork. Oliver's results are recorded in the annual report for 1870 of the Sa nitary Commissioner for the Government of India: 1st . It was calculated that this tapeworm produce d between 13 and 14 proglottids per day 36. which was designed to determine the effects of heating of cysticerci on their infectivity. a buttock of beef studded with cysticercus was given to three natives of low caste. Cysticercosis bovis was endemic in the area and T. two scolices of cysticercus within three or four months produced a T.Taeniasis saginata parasite by eating raw or poorly-cooked beef.After explaining to them the possible consequences of eating it.perhaps Oliver administered isolated scolices.In the case of a Hindoo boy of low caste. saginata in cattle by Leuckart. but in order t o examine the clinical effects of consumption of measly beef under differen t conditions. The meat they cook in their own way. A more precise study was undertaken by Ed uardo Perroncito in Italy in 1877. saginata infection in just the same way as they contracted taeniasis solium. Under standably enough. solium. SAGINATA Following the experimental production of the cysticercus of T. Indeed.30 This last patient cited is particularly surprising as it would be unheard of for a Hindu to eat beef . solium by Humbert. Two of them had no symptoms of taenia. He cooked it well. saginata had a life cycle similar to that of T. but the third. These men were under my observation for some six months. Thus. saginata 4.27 m long and containing 866 proglottids. and has never shown a sign of having tape-worm. saginata infection was common in the local camel drivers.My own sweeper ate this cyst-infected beef regularly two or three times a week for some months. 54 days later. it was a number of years befor e anyone repeated the similar experiment first done with T. 3rd . developed a T. it was finally proven that T. generally as an ordinary stew. John Oliver. and had probably eaten the meat in a very raw state. mediocanellata in about three months. who was a low class Mahomedan syce. not so much as to demonstrate completion of the life cycle. Treatment with kousso and oil of ricin on the 57th day yielded a T. made some poorly controlled experiments during 1868-1869. saginata 13. Infections may also be multiple. Although T. solium to the older anthelmintics 21. finds a single proglottis attached to or creeping about the leg. One patient treated wit h extract of kamala passed three yards of T. Cases with more t han 5 worms was exceptional although one patient was claimed to have 27 T. produced 31 specimens of T. together with the head. passed a further 11 yards . these worms rarely cause intestinal obstruction . devolve from the presence of intestinal worms. saginata. saginata. and when he seeks to free himself from this unpleasant sensation. has been removed from the gall bladder of an old man with acute cholecystitis 4. Bérenger-Férand 5 reviewed 2686 cases and found that one worm was present in 87% of persons. Observations over the centuries have sho wn that the prognosis is good in this infection since there is no likelihood of people developing cysticercosis. these infections respond well to th e newer drugs described in chapter 13. 21 Presumably they were grateful for the invention of elastic underwear! It ha s been concluded that 8-9 proglottids are produced per worm per day34. solium and Küchenmeister has a particularly graphic description of their passage which he notes may occur either in the faeces or separately: The segments pass when the patient is standing quietly and falling into his trousers. More certain is the patient of Hodson who. saginata are said to break off more easily than those of T. bovis in humans11. the clinical manifestations of infection with this parasite. ten feet long. In 1893. he suddenly has a moist and cool feeling about the legs. Proglottids of T. saginata and another. It has even been claimed that a complete T. two were present in 7.392 A History of Human Helminthology RECOGNITION OF THE CLINICAL FEATURES Although rare claims have been made for findin g C. when treated in the Khartoum Civi l Hospital with filix mas. These tapeworms might also reach remarkable lengths. 59 tapeworms. the symptom s and signs are much the same as have been described already for taeniasi s solium. Consequently. Women especially are afraid lest the proglottides should fall unperceived upon the ground when they are walking or standing.3% had three tapeworms. and then on being treated again almost immediately with oil of male fern.8% and 2. DIAGNOSIS AND TREATMENT The diagnosis of taeniasis saginata is made in the same way as is taeniasi s solium. although several cases of this complication are on record 9. for all practical purposes . . making 14 yards of tapeworm in total 1. Despite their ability to reach huge sizes. saginata was said to be slightly more resistant tha n T. Efforts were made to define the life span of eggs and cysticerci. These eggs were remarkably resistant to destruction in the laboratory by a grea t variety of physical and chemical means 15 and were found to survive for several months in pastures 35. it being estimated that each proglottid released an average of 80. then administered them to his collaborators. and the subsequent infections of humans by such cysticerci. cysticerci die between two and three weeks after slaughter of the cattle. it had no sign of life and failed to develop. Epidemiological investigations then concentrated on defining the prevalence of taeniasis in humans and cysticercosis in cattle in various parts of the world. THE EVOLUTION OF PREVENTIVE AND CONTROL MEASURES The discovery that taeniasis saginata was acquired by ingesting contaminated beef suggested that infection should be preventable by proper cooking of beef. as did th e introduction of compulsory inspection of cattle and condemnation of measl y beef. . saginata eggs in mature proglottids obtained from infected humans.000 eggs . and all were dead by nine months after infection 33. this infection was a zoonosis. A few years later. Ranso m found that they could also be killed by refrigeration at -10 oC for six days. a patent infectio n developed in a fourth person who ate an unheated C. In contrast. The latter investigator expose d cysticerci to various tempera tures. enormous numbers of eggs were discharged into the environment. each infected patient might pass about half a million eggs daily 34. like taeniasis solium. 37 In addition to these measures. As wit h T. Further researches confirmed that humans were the sole definitiv e host and cattle were the principal intermediate hosts. Studies of experimentally-infected cattle showed tha t cysticerci lived in the tissues for a variable period but that most were not viable within four months. improved methods for the disposal of human faeces helped reduce the incidence of infection in many places. solium. Dr.Taeniasis saginata 393 UNDERSTANDING THE EPIDEMIOLOGY The experimental generation of C. Ragni consumed a cysticercus which had been heated to 47 oC. Perroncito further showed that even without heating. S imilar outcomes awaited the medical student Gemelli who ingested a cysticercus heated to 45 oC and his colleague Martini whose cysticercus had been exposed to 44 oC. clarified the epidemiology of taeniasis saginata and indicated that. The organism was found to be spread wide ly but sporadically around the globe. bovis in cattle by feeding them with T. bovis. Thus. The observations of Oliver 30 indicated that this was likely then it was confirmed by the experimental studies of Perroncito 36. Nebst einem Anhange über Pseudo-helminthen. BATSCH AJ. two volumes. JUDAS A. de Chirugie et de Pharmacie Militaires 13: 230. pp 284. Gazette des Hôpitaux 92 : 183-185. KÜCHENMEISTER F. HUBER. Eine von der königlich dänischen Societät der Wissenschaften zu Copenhage n gekrönte Preisschrift. BLANCHARD R. CHRISTOPHERSON JB. 1867 2.. Traité de zoologie médicale. Taenia mediocanellata hominis. pp 500. In Japanese. Ein Buch für ausübend e Aertze. 1786 4. KÜCHENMEISTER F. London. 1921 14. Paris. pp 15-21. Parasites: a treatise on the entozoa of man and animals including som e account of the ectozoa. A case in which fourteen yards of Taenia mediocanellata were voided with the head. 1918 10. Sigismund Friedrich Hesse. Nicolas Hartsoeker et l'autre . BG Teubner. Ueber eine neue Taenia des Menschen. f pp 29-75. les deux premières.und Handbuch der Diagnose und Behandlung der thierischen und pflanzischen Parasiten des Menschen. KEAN BH. Berlin. 1922. Tapeworm hospitality. Ueber Taenia solium und T. Zittau. pp 468. 1819 9. ANDRY de BOISREGARD N. De la génération de vers dans le corps de l'homme. Versuch einer Naturgeschichte der Eingeweidewürmer thierischer Körper. Laurent d'Houry. 1700. necessitating laparotomy. 1978 18.. ANONYMOUS. RUSSELL AJ. Ueber lebende Würmer im lebenden Menschen.) Taiwan Igakkai Zasshi No. 1852 20. BÉRENGER-FÉRAND. Avec trois s lettres sur les sujets des vers.. 1893 6. Paris. Carl Schaumburg und Comp. 1. 1855. pp 677. Wien. An account of the breeding o f worms in human bodies etc. Taenia inerme de l'intestin. Observations on the Taenia solium.. J&A Churchill. Mit nach der Natur gezeichneten Abbildungen auf vier Tafeln. Edinburgh Medical and Surgical Journal 17: 384-393. translated by E Lankester. two volumes. Du nombre et de la longueur des taenias que l'on rencontré che z l'homme. and on its removal from the human intestinal canal by spirits of turpentine. BENEDICT EB. Classi c investigations. Acute intestinal obstruction by tapeworms ( . 1857 22. Tropical medicine and parasitology. 222. London.. COBBOLD TS. Ueber Cestoden im Allgemeinen und die des Menschen insbesondere etc. 1853 21. Murchison). FONTAN C. Cornell University Press. KNOX R. Ithaca. pp 266. with English summary 16.. pp 486. pp 452. Abhandlung von der Erzeugang der Eingeweidewürmer und den Mitteln wider dieselben. diagnosis and treatment.394 A History of Human Helminthology REFERENCES 1. MOTT KE. seu Zittauensis (mihi). Lancet ii: 728. Parasitism adulte et larvaire chez le meme sujet. Notizen über das Vorkommen pflanzicher und thierischer Parasiten in unser m Bezirk. pp 121-129. . Leipzig. pp 471. The Sydenham Society. g Halle. 1701 3.par M. 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Practische Monographie der Bandwürmkrankheit etc. solium 1782 Goeze recognized two forms of Taenia but little notice was taken of this observation 1852 Küchenmeister clearly distinguished T. saginata from T. saginata infection in persons who ate measly beef 1877 Perroncito infected a person with a single C. in a poorly-controlled study. saginata proglottids 54 days later 1960 Niclosamide was introduced for treatment 1977 Praziquantel was introduced for treatment ___________________________________________________________________ . saginata proglottids 1868-9 Oliver. observed T.396 A History of Human Helminthology Table 14. Various anthelmintics were used 1700 Andry drew an illustration of Taenia saginata although he called it T. Landmarks in taeniasis saginata __________________________________________________________________ BC Tapeworm infections in humans were known but the various species were not distinguished.1. solium on the basis of the morphology of the head and the number of lateral branches of the uterus 1861 Leuckart generated Cysticercus bovis in a calf fed with T. bovis and the subject began to pass T. According to Davaine 24. When deposited in moist environments. nisi rectius geniculatus dicatur. When a plerocercoid in raw or insufficiently cooked fish is ingested by a human. Eggs and gravid segments are passed in the faeces. North America. the plerocoercoid develops into an adult worm and begins to pass eggs 4-6 weeks later Definitive host: humans First intermediate host: certain copepods (Cyclops. Japan. Chile. Taenia lata Distribution: foci in Europe (especially Scandinavia and the Baltic countries).Chapter 15 Diphyllobothrium BOTHRIASIS latum AND DIPHYLLO- SYNOPSIS Common name: broad tapeworm Major synonyms: Bothriocephalus latus. eel. pike. spontaneous passage of proglottids Diagnosis: finding of eggs or proglottids in the faeces Treatment: niclosamide. the procercoid is liberated in the fish's gut and migrates to the muscles where it develops into a plerocercoid (or sparganum) up to 2 cm in length. first Thaddeus Dunus in Lucarno in 1592. described in a recognizable fashion. the worm now known as Diphyllobothrium latum. The larva develops over 2-3 weeks into a procercoid in the body cavity of the copepod. then Gaspard Wolphius in Zurich. fotus sui simillimus" 26 meaning that the broadworm of remarkable length had the scaly appearance of a snake 397 . ruff. When an infected copepod is ingested by certain species of freshwater fishes. perch. up to 10 metres in length. salmon and trout Major clinical features: abdominal discomfort. it was not until around the beginning of the seventeenth century that it was realized that more than one species of tapeworm infected humans. northern USSR. Dibothriocephalus latus. lawyer. Dunus wrote: "De lumbrico lato (mirae longitudinis): squamosus instar serpentis. praziquantel DIFFERENTIATION OF THE SPECIES FROM TAENIA SOLIUM Although tapeworms have been known since ancient times (see chapter 13). Uganda Life cycle: The adult tapeworm. lives in the small intestine with the head attached to the mucosa. it is now apparent in retrospect that two Swiss observers. Dibothrium latum. each egg hatches and the larva (coracidium) swims about until it is ingested by certain species of small crustaceans (copepods). including species of burbot. Diaptomus species) Second intermediate host: certain freshwater fish. . again reported the existence of two distinct species of tapeworms in humans80. Taenia intestinorum. Previously.3 The first of these he labelled as Taenia à épine (Taenia with a spine) and the second he called Taenia sans épine (Taenia without a spine). the hallmark upon which Platter based his distinction between the two species of worms was the shape of the proglottids. these observers did not allude to the differences between this worm and either of the two species of Taenia now known to infect humans. but generally in many pieces.. The first person to do this. similar to the fabric of the small intestine. they were shaped differently and appeared to be composed of many attached segments which could be separated from one another. it is not alive. latum. although his description is somewhat vague. ..63 Thus. each of these individual pieces was believed to have been an individual worm. In 1618. Nicholas Andry in 1700 also recognized two types of tapeworms: One has. nor is it stirred from its place. Nevertheless. solium. but more correctly it should be called the Taenia intestinorum (the taenia of the intestines) since it has no likeness to the lumbricus. but remains fixed for a long time until it is passed. has a sort of small Nipple open at the Point. probably without being aware of the previous account.a long Thorn full of knots running along the middle of its body upon the upper side. equal to it in length but not at all empty inside as it. They appear along its whole length and resemble vertebrae. Perusal of his illustrations of Taenia à épine leaves no doubt that the spine which he described as running down the middle of the entire length of the worm is in fact the medially-placed genital openings of the worm now called D. the Dutchman. However. since gourds sometimes bear square seeds.. and this became known to later authors as Taenia prima plateri (the first Taenia of Platter): One is characterized by a kind of membranous skin. His descriptions were incomplete and to some degree erroneous. but at every Joint upon the sides. very long taenia of the same type were observed. and this became known as Taenia secunda plateri (the second Taenia of Platter) to later authors.398 A History of Human Helminthology except that the leading joints were attached and supported each other.On this fascia there are generally transverse lines about a finger's breadth apart. It probably refers to T. and about a finger's breadth wide. Whereas his predecessors and contemporaries called all tapeworms "Lumbricus latus". He called the first of these.63 The second form he called Taenia longissima. Adrien van der Spiegel (Spigelius). The worm is rarely passed whole.. was Felix Platter (Platerus) in Basel (Switzerland) in 1602. Platter discerned two forms of tapeworms passed by humans. saginata: On another occasion. as is the lumbricus.. This they call the Latum lumbricorum (the broad intestinal worm).. but may possibly have been T.The other wants this Thorn. are called the vermis cucurbitinus. He was unaware that tapeworms had a head and does not appear to have realized that tapeworms were living organisms. however. swelling out in the intervals between them. they are only pieces broken off from the fascia. These segments. called a cucurbitinus... solium or T. respectively. Eschricht published the first detailed description of the anatomy of the adult worm28. as he called them)13. to indicate that it was the broad worm with the grooved head18. examination of his figures of Taenia sans épine clearly indicates that the small nodules that he described at the margin of each proglottid are the laterally-placed genital pores of T. In 1750. Bremser in 1819 again described the worm and created a new genus. Shortly thereafter (1779). For example. In this work. he emphasized the "stigmata umbilicialia" of the broad tapeworm and the "stigmata lateralia" of Taenia. It is not certain who first saw the head of D. considering them to be pulmonary openings). Several epidemiological observations. noting its attenuated shape and the two suctorial grooves. ELUCIDATION OF THE MODE OF TRANSMISSION The origins and mode of transmission of this parasite remained obscure for many years. In 1777. one quarter of the inhabitants of Geneva were said to be infected21. saginata. but its nature was by no means clear. in the early parts of the nineteenth century. . Nine years later. Finally.Diphyllobothriasis 399 Similarly. then this was changed to Dibothriocephalus latus by Lühe in 189949. latum following the first description of a tapeworm head by Edward Tyson in 1683. it became apparent that this infection had a restricted geographical distribution. the parasite was transferred by Lühe50 in 1910 to the genus Diphyllobothrium erected by Cobbold in 185720. pointed towards the direction in which the solution would be found. Charles Bonnet published his study of human tapeworms. "leaf" and "groove" or "sucker". then went on to outline the appearance of the proglottids ("rings". saginata and the body of Diphyllobothrium 12. This indicated to many commentators that there was something unusual about the mode of transmission of this infection. in Geneva. latum from other tapeworms. the key distinguishing feature for Andry was the position of the genital apertures (although he did not recognize them as such. In 1841. Diesing renamed the parasite Dibothrium latum 25. von GleichenRusworm likewise described the scolex of the worm31. The generic name was derived from a combination of the Greek words (DIS). (PHYLLOS) and (BOTHROS) meaning "two". Scandinavia and the Baltic regions. renaming the worm Bothriocephalus latus. These infections were at first unknown outside Europe and were thought to be most common in Switzerland and adjacent areas of France. however. however. Bonnet corrected his earlier publication and described the head of the broad tapeworm in detail for the first time. Thus. As observers became more confident in their ability to differentiate D. but he included a figure showing what Blanchard11 later called "un être fanstastique" (a fantastic being) with the head of a T. More than fifty years were to pass after Abildgaard's pioneering experiment before Steenstrup published his theory of the "Alternation of Generations" (see chapters 2 and 4). believed that he had proved this mode of infection and adduced two pieces of evidence to support his view. then by Schubart's friend. Knoch. Probably unaware of Schubart's findings. concepts about the transmission of D. however. these observations did little to help answer the fundamental question of the mode of transmission. They agreed that hatching took several weeks or months to occur. filled with mature eggs. for example. As early as 1747. Abildgaard became interested in a cestode worm that lived in the abdominal cavity of the little fish known as the stickleback. he attempted to infect a number of potential intermediate hosts by introducing embryos to various aquatic animals but met with no success. which had no reproductive organs. ideas abounded. suffered from the tapeworm more commonly than did populaces living in other areas81. such as Vogt91 held that transmission was direct with a human to human cycle in which humans ingested eggs in food contaminated with sewage. First. He died before he could publish the observations in detail but notice of the finding was given. Secondly. The time was not ripe for a proper appreciation of such revolutionary discoveries. he found . Verloren in 185577. Following dissemination of Steenstrup's ideas on the alternation of generations. latum. first by Kölliker in 185176. depending upon the temperature. He wondered whether the worms in the fish could be an immature form of the bird parasite so he fed some of them to domestic ducks. he administered embryonated eggs and non-embryonated eggs to two dogs. These had been mentioned by Andry in 1718 and primitive drawings had been made by Goeze in 178232. made the very perspicacious observation that people who lived on the banks of rivers. Küchenmeister in 1855 described the egg as having a brittle shell with an opercular opening and containing a limpid vesicle with six hooklets. Some scholars. Petersburg (Leningrad). Schubart of Utrecht hatched ova of D. nor did the confirmatory observations of Creplin22 with Schistocephalus and Ligula receive the acceptance they deserve. tapeworms. latum in water and observed the liberated embryo with its mantle of cilia. which looked just like those occurring in mergansers 2. and thus opened up new vistas for understanding the manner of transmission of diphyllobothriasis. R Leuckart in Germany (1863) 48 and Bertolus in France (1863) 8 all observed independently the hatching of ova. Nevertheless. He perceived certain resemblances between this worm. in the ducks' intestines. Knoch in St. latum generally fell into one of two categories. in 1862. attention was paid to the ova of D. and lakes where there was plenty of fish.400 A History of Human Helminthology Nevertheless. Initially. the Finn. and the tapeworms that he had seen in mergansers and other fish-eating birds. Russia (1862) 43. rapids. Four months later. This idea that consumption of fish might be important in the acquisition of tapeworm infection received a boost with a discovery of Peter Abildgaard in Copenhagen in 1819. Abildgaard was delighted to find later. Herman Spöring. This notion was amplified when Stein in 1882 drew attention to the fact that many orthodox Jews were carriers of D. Küchenmeister writing in 1855 thought that this was unlikely. kept returning to fishes as potential intermediate hosts. together with the precedents established with various trematodes (see chapter 4) suggested to many that the intermediate hosts were likely to be aquatic animals. This idea flowed from the Abildgaard's demonstration. found two worms. decided to look for the intermediate host of D. Others. with variable numbers of unencapsulated worms being found in the muscles and viscera. Estonia (present-day Estonskaya SSR. In the case of Diphyllobothrium. it is clear that these dogs had acquired natural infections. to infect trout in a stream near his home by contaminating the water with large quantities of eggs and hatched D. plerocercoids of . DISCOVERY OF THE PLEROCERCOIDS AND THE FISH SECOND INTERMEDIATE HOST Since attempts to infect potential hosts with larvae derived from eggs were unsuccessful. As it was known that other species of bothriocephali could be found in animals or birds which either primarily or exclusively ate fish. Küchenmeister thought it more likely that the larvae might live in snails which could be ingested accidentally with fruit and vegetables. referred to earlier. and this was not the habit of the populace45. latum 9. however. without success. in the other animal43. USSR). He therefore examined fish brought to the market in Dorpat from Lake Peipus and surrounding regions. and soon found young bothriocephali in pike (Esox lucius) and burbot (Lota vulgaris). More than 90% of the fish in the market were so infected. Such worms had been seen previously by Knoch in St. This hypothesis was strengthened by the discovery in the 1850's that the taeniid cestodes underwent migration and metamorphosis in mammalian intermediate hosts. In fact. then after another six weeks.Diphyllobothriasis 401 diphyllobothria in various stages of development in one dog. Max Braun in Dorpat (Tartu). and Leuckart attempted. The alternate view was that ova developed into larvae in an intermediate host before ingestion by humans. attention turned to the other end of the life cycle. for he was under the misapprehension that infection could only be caught by eating fish intestines. for when similar experiments were repeated by other investigators in non-endemic areas. however. solium 82 Despite earlier suggestions that fish may be related to the acquisition of infection. Bertolus postulated that Ligula nodosa in salmon was the intermediate form of D. 45 and 53 cm long. Petersburg but he had not realized what they were. latum among the fish eaten ordinarily by the people living in his region. latum larvae48. the known association of the infection with lakes and rivers. In retrospect. particularly Leuckart in Giessen and Grassi in Italy. no worms matured. that some cestodes found in the intestinal tract of fish only matured after ingestion by some predaceous bird. latum although they never ate raw meat and were not infected with T. Subsequent investigations showed that a number of other species of fish. a large number of D. thrived. although. while the third subject passed only fragments of tapeworm16. corresponding initial parts of B. DISCOVERY OF THE PROCERCOIDS AND THE CRUSTACEAN FIRST INTERMEDIATE HOST The question still remained as to the manner in which the precursors of the plerocercoids reached these fish. another produced three parasites. a series of feeding experiments to prove that these plerocercoids could develop into adult D. they began to feel ill and complained of abdominal pain.The dog. latum.402 A History of Human Helminthology Diphyllobothrium may have been seen in fish as early as 1688 by PJ Hartmann. In the intestine . A few days later. sometimes with positive results. they can only be attributed to the infection which took place. but on other occasions he failed to find any diphyllobothria. he found worms which resembled the original plerocercoids but which grew progressively in size. one student expelled two specimens of mature D. At first glance. In 1883. After about three weeks. he did not relate them to the broad tapeworm infecting humans36. of course.16 Finally. Braun infected a number of dogs and cats. After treatment with a variety of anthelmintics. the head unfolds and one recognizes the suction grooves on it"16. they did not look much like Diphyllobothrium for the head was usually withdrawn but Braun wrote that if the worm: "is placed in warm water or egg white. Braun began. latus. Braun found five round holes in the . although not completely. infected a dog which up to that time had only been fed with its mother's milk: I was able to give a three-week-old dog 17 pike bothriocephali in one day by forced feeding. Braun. In order to be absolutely sure that the infections were not acquired naturally in some other manner. which ingested only boiled cow's milk...17. The worms found by Braun were between 8 and 30 mm in length and appeared to be analogous to cysticerci and echinococci as they were sexually immature. latum. These results were confirmed several years later by Grassi and Ferrara34 then by Zschokke. latum. he gave plerocercoids to three dogs then sacrificed them four.. latum eggs were found in the stools of each student. he called them plerocercoids 16. including perch (Perca fluviatilis) and ruff (Acerina cernua). Braun investigated the effects of giving plercocercoids to humans. On 15 October 1882. Initially. he gave three or four worms obtained from pike to each of three medical students who were not carriers of D. eight and eleven days later. in 1881. On examining the faeces on 18 November. they were treated with ethereal extract of male fern. but because of its continued howling. at the suggestion of Professor E Rosenberg. Since diphyllobothriasis was rare in dogs and was never seen in cats in Dorpat. had to be killed ten days after infection. I found sexually immature bothriocephali 14-15 cm long which matched. were also infected sometimes. In their intestines. . while working in Lausanne. Encouraged by this discovery. When he searched the youngest perch. he found two of these worms lying free in the stomach mucus of a tiny perch. then together with this intermediate host. Rosen decided to repeat these experiments in a modified form. if possible. latum. latum with the head of each worm pointing away from the lumen of the stomach towards the submucosa. Rosen then examined them carefully each day for up to three months between October 1916 and April 1917. Janicki between April and August 1917 examined the stomach contents of 82 Lota vulgaris. little more than half a millimetre long but which were clearly very young larvae of D. Switzerland in the summer of 1916. salmon (Salmo salvelinus). Cyclops. I was able to formulate the idea that the primary . Two of them still contained a plerocercoid of D. 40% of the Lota were infected. The results were absolutely negative70. Constantin (Konstanty) Janicki who. On 25 June 1917. Janicki found tiny worms. A few days later. he mostly found enormous quantities of Gammarus. made a similar observation. the stomach contents of which revealed mainly the copepods. to trace the development of the worm from its appearance in the primary intermediate host to the plerocercoid stage. Although this idea was later abandoned by Braun in favour of a direct infection of fish. the concept was seized upon by the Pole. encapsulated within the stomach wall. he began to examine small perch systematically for even younger stages of plerocercoids. Switzerland to collaborate with him40. When his attempts at direct infection were unsuccessful. 998 Perca fluviatilis and 3 Esox lucius obtained from the market in Lausanne.Diphyllobothriasis 403 stomach of a burbot. he invited a fellow Pole named Felix Rosen who was working in Neuchatel. latum develop into cysticerci in an as yet unknown intermediate host. Thereupon. both directly under the dissecting microsocope and in histological sections made from paraffin blocks and stained. Janicki had first tried to infect fish directly but had failed. This observation led him to propose that ciliated embryos of D. By this means he hoped to determine the nature of their food which might give him some clue to a possible primary intermediate host then. Diaptomus and Bosmina. In the stomach of Lota vulgaris. formalin-fixed material. Many of the perch were infected and in their stomachs he found mostly water fleas and copepods (small crustaceans). The other three holes were empty but Braun found the worms not far away in the stomach wall between the glandular and muscular layers. burbot (Lota vulgaris). they reach the gut of a fish where they are freed during the process of digestion. perch (Perca fluviatilis) and pike (Esox lucius) with large numbers of ciliated D. then penetrate the intestinal wall of the fish and migrate into its body wall16. mostly with plerocercoids in the stomach. This led him to the conclusion that a copepod must be the primary intermediate host: "Thanks to this evidence. He infected hatchlings of trout (Trutta species). latum larvae. Since Janicki had used unstained. he found another worm in a perch which contained only Cyclops and Diaptomus in its stomach. the Gammaridae... a primordial mouth developed at the other end. moreover. it grew and became more elongated in shape. Rosen infected six small trout on 6 August 1917 by placing them in an aquarium containing large numbers of copepods which had been infected for six weeks. did not eat much plankton. while still free in the stomach lumen. Plankton seemed to him to be the least likely since Lota vulgaris. he began experiments with plankton on 17 June 1917. 0. strenuus infected with one to ten oncospheres in the body cavity: At first I did not observe anything special.404 A History of Human Helminthology intermediary host must be sought among the copepodae" 38. Undismayed. These findings were confirmed two years later by Galli-Valerio when he infected successfully C. then Redlich showed that D. all the specimens examined were found infected. he had no luck until he turned his attention to the copepods in the plankton. Subsequent studies revelealed that after the ciliated larvae. latum eggs obtained from the faeces of a dog30. Again. At first. penetrated the gut wall and reached the body cavity. This stage he called a procercoid 70. it had reached 0. Rosen decided that the first intermediate host must lie within one of the following four types of food: plankton. In rapidly draining the water from beneath the cover slip. he found large numbers of C. so that the pressure of the latter removed the little fat droplets. however. or in any case of a species very closely related to the true host. One after the other.6 mm in length. By examination of some of these fat droplets at a higher power. whereas other plankton eating fish such as the Coregonae were never infected.I confirmed that several were nothing more than oncospheres which were already in the body cavity.5-0. He collected plankton form Lake Neuchâtel then mixed it with large numbers of larvae. On 24 June. all with negative results. My astonishment was then immense. Further observations revealed to Janicki that. it became attached by a narrow neck then finally fell off when the larva was between two and three weeks of age and 0. strenuus with D. particularly when Cyclops viridis ingested then actually digested the larvae. Meanwhile. these young worms carried a caudal appendage furnished with hooks and that this was cast off before the parasite penetrated the mucosa38. In the meantime.. He therefore examined the latter three groups. all seemed hopeless. The numerous fat droplets which filled the body of these crustaceans. was ingested by a Cyclops.70 Rosen then found that Diaptomus gracilis was also infected.. it lost its embryonic envelope. the examination had no more obstacles.. At one end.024 mm in diameter. being a fish of the deep. One trout was .There was no longer any doubt that we were in the presence of the primary intermediary host.. Rosen in Neuchâtel arrived at a similar conclusion. graciloides was a very efficient intermediate host67 In order to complete the life cycle experimentally. a spherical appendage containing the hooks evolved. In that location. particularly at each extremity. but to a lesser degree. having approached the problem from a different angle. prevented a very detailed observation. and the Oligochaetae. This time his efforts were to be crowned with success. By the tenth day.2 mm in size and the structure had begun to differentiate. insect larvae. The development passes from the oncosphere to the plerocercoid by an intermediate larva. became professor of zoology at Warszawa.Diphyllobothriasis 405 killed six hours later and free procercoids were found in the stomach contents. Von Bonsdorff has portrayed succinctly their subsequent paths: "Janicki. Rosen concluded his paper by writing: The life cycle of Dibothriocephalus latus is now completed: (1) by the negative result of the direct infection of fish by ciliated larvae. Unfortunately. In this latter paper71. palpitations during the night. The clinical manifestations were put on a more certain basis when humans were infected experimentally. few serious symptoms occur from which it can be perceived that an individual carries this foulness in his body before they pass unexpectedly. The medical students infected by Braun17 developed malaise and abdominal pain three weeks after ingestion of plerocercoids. some with and some without caudal appendages. Rosen published another paper which provided further details. (2) by the positive result of a mode of development in cestodes unknown until now. he believed that the larvae could be considered plerocercoids and they migrated from the gut into the muscles and viscera. Rosen found procercoids in the stomach wall. the ciliated body emerging from the D.. it is felt.... swollen abdomen.70 The following year. because he had carried out the last decisive experiment. An unpleasant controversy between the two followed.. and concluded that the effects were little more than discomforting with transient diarrhoea at the onset of patent infection after two . at which time they occasion great fright on being found. fainting and epigastric pain could all be caused by D. with Janicki replying to Rosen's attack39. latum egg was called a coracidium and the plerocercoid was defined by the development of two suckers71.the procercoid. In a fish killed the next day. Abbotts Smith in 1863 wrote that anal itching. tried to take the whole credit for himself and launched a violent diatribe against Janicki. what had begun in friendship and teamwork between Janicki and Rosen turned sour. unless something else happens. Le Bas has described in detail the clinical features in three humans infected experimentally. In particular.63 With the passage of time. who was an eminent parasitologist. Thus. that is. The symptoms become worse when an intestinal worm dies or if a segment is broken off from the others and putrefies.. vertigo. There is a pressing desire to rake food much more often than was customary and a certain heaviness in the stomach. nausea. however. Rosen. If anything is in the stomach.. all manner of ills were ascribed to this worm. the existence of two intermediate hosts. Four days after infection. RECOGNITION OF THE CLINICAL FEATURES Felix Platter was remarkably accurate in his summation of the clinical features of this infection when he wrote in 1609: While taeniae remain in the body. an itchy nose. latum 1. Rosen made no further scientific career"14. Sixty of the infected people were treated with anthelmintics . latum infections was at one time put at 20 years or more. was astonished to find vast numbers of D. This was based largely upon the finding of infected patients in North America many years after emigration. Tarassov. this was interpreted as evidence for the development of partial immunity86. could have accounted for this result. such as changes in eating and cooking habits. then challenged himself with six plerocercoids 3. One of three volunteers infected by Le Bas in 1922 was RT Leiper. These observations suggest that little immunity to challenge infection develops. Statistical analysis revealed increased frequencies of a sensation of hunger. were found to be infected with D. Even more valuable than this study was a comparison of symptoms between infected and non-infected persons living in an endemic area. fatigue. In one such study. The duration of D. Whereas the other two subjects were cured completely by carbon tetrachloride administration soon after infection. In endemic areas. The most usual symptom was of patients complaining of passing segments of worms intermittently. diarrhoea. most of the uninfected persons being young children. Nevertheless. numbness of the extremities and a craving for salt in infected persons74. The worms passed out in a bundle.7 metres in length after treatment78.406 A History of Human Helminthology to three weeks. Leiper passed less tapeworm heads than the number of plerocercoids he ingested. latum. Even more heavily infected was a 66 year old man who passed 106 tapeworms weighing 400 grams33. but many other factors. the agonizing delivery lasted ten minutes and the parasites filled up half a chamber pot72. who had carried out this study. the patient assisting at the delivery by tearing at the mass with both hands while at the same time shrieking like a woman in labour. followed by vague dyspeptic symptoms46. There is no doubt that infection may last as long as six years. infected himself in 1932. and this concept has been supported by a number of other investigations. One Russian woman living in the USA passed a single worm 8. however.three years later. 125 of the 143 inhabitants of a village in Karelia. had very large tapeworms or incredible numbers of them. While in Cairo in 1928. a patent infection developed and treatment five weeks after challenge produced two heads and 6. Some patients. latum ova. Perhaps the record in terms of total length.3 metres of . 20 were reinfected whilst 40 were not. he had an acute attack of dysentery and on examination of his stools. was set by the Russian man who passed 14 worms totalling 83 metres in length62. He continued to observe the passage of these eggs in his stools for the next ten months until termination of the infection with anthelmintics. however. but before it was realized that diphyllobothriasis is endemic in parts of that continent.5 months after the original infection. he was well for the next few years and did not notice any proglottids in his stools. though. In Switzerland. Leiper believed that this was a persistent infection as he had had no opportunity for acquiring a natural infection during the interval47. professor of helminthology in London. the majority of patients had small numbers of relatively short tapeworms. USSR. treated himself. a 21 year old woman passed at least 90 adult worms after therapy. Estonia (USSR). and weakness forced him into a sanatorium. the faeces of patients who were seen in his clinic were examined systematically for D. Thereafter. he began to examine the wet blood films and found that although the numbers of red cells were reduced markedly. and this is probably the normal state of affairs. he reported his experiences at a Congress in Berlin. lost 8 kg in weight. the . In 1936. latum eggs and. Tarassov infected himself with seven more plerocercoids. Reyher encountered a similar situation in a 30 year old man. he had seen a number of cases of pernicious anaemia. Finally. CORRELATION OF PERNICIOUS ANAEMIA WITH D. the Congress received his communication with reserve. The results of this serendipitous bedside observation. In 1883. Gustav Reyher in Dorpat (Tartu). there was no significant immunity several months and several years after the first exposure to D. her general health had returned to normal. JW Runeberg in Helsingfors (Helsinki).Diphyllobothriasis 407 worm. She also complained of intermittent diarrhoea and on one such occasion had passed a segment of D. and he also noted that the white cells were often reduced in number. 12 of 19 patients with pernicious anaemia were also infected with D. While these results could be interpreted as indicating transient immunity one and two years after the initial infection. saw a 66 year old woman who became steadily weaker and paler during the course of a year. he treated himself and expelled 38 metres of tapeworm with seven heads86. they were often larger than normal. he began to pass eggs in his faeces 14 days later. anthelmintic therapy seven weeks later resulted in four heads and 26 metres of tapeworm. a disease which had been defined by Biermer in 1872. Nevertheless. were finally published in June 188668 Independently of Reyher. but that within a few weeks. Reyher therefore treated her with extract of filix mas and was surprised to find that not only was the worm expelled. latum. Similar challenges one and two years later failed to produce patent infections. all with a fatal outcome. it is far more likely that those challenges were made with non-infective plerocercoids. latum. treatment resulted in an equally striking cure. Five weeks after infection. In September 1886. he had much abdominal pain. an anthelmintic was given. Certainly. that in addition to these two investigators. four years after the original infection. While harbouring the worms. latum and all of these persons were cured by expulsion of the worm73. In late 1883. Finland had been following a similar line. and had been struck by the fact that the majority of patients had D. which was skilfully followed up. Six months later. Rehyer then began to collect a series of such cases and by 1884 had seen 12 patients. He diagnosed her as suffering from pernicious anaemia. It seems probable. however. LATUM INFECTION In July 1877. latum in their intestines. he again infected himself with six plerocercoids and patent infection occurred. if they were found. the outcome in the early years of treatment depended upon elimination of the parasites. Finally. the erythrocytes were enlarged and there was a mild leucopenia with the white cells being hypersegmented. However. Petersburg. patients were deemed to be so ill that they were subjected to blood transfusion (with all its attendant complications in those days). latum was found in the intestines of patients dying from pernicious anaemia. thus confirming an aetiological relationship. whether D. it seems that Reyher ought to be accorded the greatest credit for the discovery. latum segments75. and in contrast to the anaemia seen in hookworm infection. This anaemia could not be differentiated clinically or haematologically from idiopathic Addisonian pernicious anaemia. but in the small number of persons with severe tapeworm anaemia. it gradually became apparent that a small proportion of infected persons did become anaemic. In some instances. prior to anthelmintic treatment. a pathologist in St. including Hoffman. The contention that some cases of pernicious anaemia were dependent upon the presence of diphyllobothria in the intestines was supported strongly by some authorities but disputed hotly by others who claimed that the association was a mere coincidence. professor of medicine in Dorpat. and Albrecht. the discovery of effective anthelmintics has ensured a favourable outlook for patients with this infection.408 A History of Human Helminthology idea of a causal relationship between broad tapeworm infection and pernicious anaemia arose simultaneously in the minds of a number of other investigators. This anaemia was not the type recognized in iron deficiency. the haemoglobin concentration being only one sixth of normal. made a rapid recovery after anthelmintic administration produced the passage of a large quantity of D. For example. Albrecht used to indicate in his reports. According to Wiltschur (1893) (cited in14). a 13 year old boy who presented in 1887 with a severe anaemia. In retrospect. even before 1883. but in many patients. The demonstration of the efficacy of liver (which contains vitamin B12) then the preparation of pure vitamin B12 for injection. . The prognosis for the vast majority of patients was good. the anaemia resolved after elimination of the tapeworms. Nevertheless. followed closely by Runeberg. he never published his observations. and the development of safe blood transfusion procedures has revolutionized management of such patients. but it must be remembered that. It was recognized that only a small proportion of infected persons became anaemic. The similarities between this anaemia and idiopathic pernicious anaemia were striking. the intrinsic factor was secreted into the gut. In that same year. Minot and Murphy showed that patients with idiopathic pernicious anaemia could be restored to health by eating half a pound of raw liver daily. Later laboratory studies showed that the parasite was able to take up both free vitamin B12 as well as that bound to intrinsic factor (reviewed in14). then the complex was absorbed in the terminal ileum. A number of theories were proposed. He then found. even though the parasite persisted 37. the white cells were slightly reduced in number and their nuclei were hypersegmented. combined with the extrinsic factor in the diet. including the production of toxins by worms and allergic reactions. von Bonsdorff suggested that tapeworms interfered with the interaction between extrinsic factor and intrinsic factor.5% of infected persons were anaemic. This observation was then confirmed using radiolabelled vitamin B12. as this contained a high concentration of vitamin B12 (some fifty times that seen in T. In tapeworm anaemia in contrast. that tapeworms competed with the host for dietary vitamin B12 and accumulated large quantities of the vitamin within their substance 15.1-0. the red cells were large (macrocytic). Further studies of patients with idiopathic pernicious anaemia indicated that the anaemia was a consequence of a deficiency of an extrinsic factor. using a biological assay. In 1948. there was a transient fashion for treating patients with idiopathic pernicious anaemia by parenteral administration of an extract of dried fish tapeworm. even though the allergic theory was held tenaciously for many years by Tötterman87. It was then discovered in 1929 by Castle and his colleagues that the production of an intrinsic factor in the stomach was requisite for absorption of the extrinsic factor. elucidation of the pathogenesis of idiopathic pernicious anaemia. Understanding of the nature of tapeworm anaemia followed. . In 1926. but these did not stand the test of time. Isaacs and co-workers tried this treatment in tapeworm anaemia and found that the anaemia resolved. a high concentration of which occurred in the liver. Indeed. and the iron stores were normal. in Finland. at that time. The anaemia was clearly quite different to that seen in hookworm disease where the red cells were small (microcytic) and depleted in haemoglobin (hypochromic) and the body stores of iron were greatly reduced.Diphyllobothriasis 409 INVESTIGATIONS OF THE PATHOGENESIS OF TAPEWORM PERNICIOUS ANAEMIA The recognition of anaemia in association with diphyllobothriasis led to attempts to both delineate the nature of the anaemia and to define the mechanisms by which it was produced. Thereupon. saginata). step by step. a mere 0. the genesis of idiopathic pernicious anaemia itself was unknown. Thus. vitamin B12 was discovered and found to be identical with extrinsic factor. latum was obvious if patients passed proglottids and brought them along for identification. it became possible to diagnose infection by microscopical examination of the stools. For example. Birkeland reviewed the literature and suggested that there may be a racial and familial predisposition to the development of anaemia. In 1956. These included a low dietary intake of vitamin B12. This was followed by the demonstration that absorption of radiolabelled vitamin B12 (Schilling test) from the bowel was impaired in both patients with tapeworm pernicious anaemia and in the majority of tapeworm carriers who had normal haemoglobin levels59. the coincidental presence of atrophic gastritis with a consequent reduction in the production of intrinsic factor5. Nyberg and Östling confirmed that vitamin B12 levels were low in the serum of persons with tapeworm pernicious anaemia61. It is uncertain who first applied this to diphyllobothriasis. whereas the man with 106 worms was grossly anaemic with a haemoglobin concentration of 25%. THE SEARCH FOR EFFECTIVE TREATMENT The anthelmintic therapy of diphyllobothriasis has been similar to that of the other major tapeworm infections of humans (see chapter 13). physicians in endemic areas realized that it was necessary to exclude diphyllobothriasis in patients with this form of anaemia.410 A History of Human Helminthology Furthermore. having a haemoglobin level of 95% on the old Sahli scale. With the discovery that helminth eggs are passed in the faeces. In 1932. Küchenmeister in his textbook of 1855 regarded diphyllobothriasis as the most easily treated of the tapeworm infections and considered that filix mas and pomegranate root were the most satisfactory medicaments45. A large number of anthelmintics with . the intensity of infection did not necessarily correlate with severity of anaemia.60. for this complication was seen more commonly in Finns than in persons of other nationalities 10. but Davaine in his textbook of 1860 provided an illustration of the appearances of such eggs in the faeces23. the location of the worms in the gut (von Bonsdorff has proferred some evidence to suggest that anaemia is more common in people in whom tapeworms are sited in the jejunum rather than lower down in the bowel). latum infection and pernicious anaemia was appreciated later that century. it became apparent that a number of other factors were necessary to precipitate anaemia in the small proportion of infected persons who became anaemic. DEVELOPMENT OF DIAGNOSTIC METHODS The diagnosis of infection with D. and finally. When the association between D. the woman with 90 tapeworms cited earlier was not anaemic. Thus. and subsequent experience has shown that almost all patients are cured with this drug. however. It has now been shown that Diphyllobothrium infections have been present in Europe for many hundreds of years. As more such cases were reported. sporadic cases of infection were noted in patients in North America. smoked or cured.79. Five years later. Stiles predicted in 1907 that this would happen in upper Michigan since its population contained immigrants who not only brought their tapeworms with them. Szidat reported that the characteristic eggs were seen in the intestinal contents of a cadaver which had been recovered from a peat bog in East Prussia. Considerable efforts were then expended on locating endemic areas and on identifying the primary and secondary intermediate hosts in those areas (reviewed in14). In 1944. More recently. it was believed at first that these infections were merely caused by long-lived tapeworms acquired before emigration. D. praziquantel was used in diphyllobothriasis 6. diphyllobothriasis had never been found outside of Europe21. latum were found in a number of fish caught in the Great Lakes. and who had never left the country57. latum eggs were found in faeces at a location near Bremerhaven (Feddersen Wiere). the body was thought to have been buried about 500 AD84. however. areca nut. carbon tetrachloride. dried. In the latter part of the nineteenth century. Since all of these people were immigrants. This idea became less tenable when in 1901 a case of native infection was reported in a French Canadian who had never been outside of Canada and rarely outside the province of Quebec35. Nickerson reported D. latum infection in a three year old boy who was born in Minnesota of Finnish parents. larvae of D. or have been infected experimentally. the majority of infections . At the time Cobbold wrote his textbook in 1864. In 1977.Diphyllobothriasis 411 variable efficacy and toxicity followed. Since freshwater fish were not imported into the United States from Finland. In support of this view. it passed beyond doubt that broad tapeworm infection had been introduced and become endemic in North America. niclosamide was introduced and was shown to cure about 70-80% of patients66.19. UNDERSTANDING THE EPIDEMIOLOGY Investigators of diphyllobothriasis realized that the infection was endemic in areas where people were in the habit of eating improperly cooked fish and where there were inadequate facilities for the disposal of waste products. either fresh. where excavations brought to light remains dated between 100 BC and 500 AD41. In the 1960's. most workers came to the conclusion that humans were the most important reservoirs of infection. including thymol. In fact. particularly around the Great Lakes. but retained their Baltic habit of eating uncooked fish. mepacrine and a preparation of the Finnish broad buckler fern. Although many animals have been found infected in nature. dichlorophen. it was concluded that the infection must have been acquired locally. latum.f. . latum.5%) c. probably as a result of their dietary customs10. otters. oregonensis 29. around 70% of the population of the western shore of Lake Peipus in Estonia were infected in 1926. latum was infrequent previously. Esox lucius and Lota maculosa 88. ova in human faeces (80%)53. Similarly. D. bears and cats can harbour adult D. in Finland. Since it was known that carnivores. vitreum. as their inputs have not been subjected to precise mathematical analysis. In 1947.412 A History of Human Helminthology occurred in female Jews who were in the habit of tasting raw fish to test their skill in flavouring it. including dogs. while plerocercoids were found in Stizostedeon canadense-griseum. Procercoids were shown to develop in D. about one quarter of them in Europe and most of the rest in the USSR with small foci in North America. foxes. On the other hand. Very high rates of infection were found in the Baltic region. In some areas. silicoides53 . On the other hand. irideus proving to be secondary intermediate hosts56. Petersburg (Leningrad) in 1781. Continued observations revealed that infection was not only endemic in fish in Lake Superior and its surrounds. S. eggs from dog faeces were much less likely to hatch active coracidia (1. but also in lakes which drained through Lake Winnipeg into Hudson Bay53. investigations in the USSR subsequently showed that eggs from dogs developed almost as frequently as eggs from humans. Eventually. the high frequency of dogs in the area suggested that these animals may be an important reservoir of infection. A number of studies were consequently undertaken to determine the primary and secondary intermediate host of infection in this region. frequencies varying between 0 and 100% were found in different parts of the country.which had long been one of the best known zones of endemic diphyllobothriasis. In any case. The relative contributions of the various definitive hosts remains obscure. with Salmo lacustris and S. Stoll estimated that there were just over 10 million people infected with D. such as on the Volga River in the USSR69. South America and Japan83. including Siberia62. the parasite was introduced into Chile and became established in the Andean Lake District some 800 kilometres south of Santiago. Within the Soviet Union. construction of the Moscow Canal allowed the development of permanent new foci of infection. silicis and D. parasitism was most frequent in the Finno-Ungarian linguistic group. industrialization altered the ecology and favoured the spread of infection. for example. Similarly. Moreover. albeit more slowly85. This region was at first regarded as the centre of infection. Similarly. but it became apparent that the worm was widespread within the USSR. it was found that heavy infections in fish occurred in some lakes near which there was a very sparse human population. however. endemic foci of infection were found in Eskimos in northwest Canada and in Alaska. Subsequent surveys indicated that the prevalence of infection in Leningrad before the Second World War was somewhere between 5 and 10% of the population. the broad tapeworm had been first reported by Pallas in St. Increased intensities of infection sometimes occurred around new reservoirs in regions where D. such as a proposal to ban the importation of Canadian fish into the USA89. The reasons for this welcome disappearance of the parasite are by no means clear4. What is clear is that infection could have been prevented by thorough cooking of fish. The two other major weapons which could be used in some situations were improvements in sewage disposal systems and the mass administration of anthelmintics. from migrating and spawning27. a number of other ways have been mooted to impede the spread of infection. in places where a significant animal reservoir of infection was thought to be present. Some of these were quite impractical. Onchorhynchus species. Using these principles. The same cannot always be said for diphyllobothriasis in more recent times in parts of Europe and Asia. in Japan the installation of dams prevented the second intermediate host. Thus. latum infections have spread in some locations such as in North America.Diphyllobothriasis 413 construction of water power plants sometimes had a helpful effect. Apart from health education. studies of the dietary habits of the population. treatment of sewage with a killing solution such as formaldehyde or chlorine before discharge into lakes or streams. they recommended the following measures: investigation of infection in copepods and fish. Nevertheless. When Petrushewsky and Tarassow described their field investigations in Soviet Karelia in 1931-32. reporting of all human cases to a central register. Magath in 1933 included among his recommendations for the control of infection in North America. Some doubts surrounded the value of these measures. mass examination of the people for tapeworm eggs in faeces. and further surveys of the extent of infection52. At one time. but it provided a tool which could be exploited commercially. undertaking a campaign to discourage feeding of raw fish to dogs. improved sanitation. whether it be wild feral animals or domesticated dogs and pigs85. these recommendations were not put into practice in any organized way. Needless to say. More important was the demonstration that freezing fish for 48 hours at -10oC killed plerocercoids 53. destruction of expelled parasites. examination of the stools of all Baltic immigrants. freezing of fish in commercial houses. the infection had become rare in that city. they have regressed in other regions. it was said that: "no good citizen of Geneva was without his tapeworm"4 but by the end of the nineteenth century. Not only was this of value in the domestic environment. though. THE EVOLUTION OF PREVENTIVE AND CONTROL MEASURES Although D. health education. Thus. have militated against this hygienic practice in many places. however. an energetic campaign has been carried . education of people to cook fish properly. Habit and custom. diphyllobothriasis does not now seem to be of major importance in that region. organized treatment campaigns. and periodical review of the results62. D. 1863 2. URSI This parasite was described in the brown bear (Ursus arctos) in Alaska by Rausch in 1954. pp 245. REFERENCES 1. ABBOTTS SMITH M. ABILDGAARD PC. was first described by Nybelin in 193158. however.000 in 1959 to just under 3. On human entozoa: comprising the description of the different species of worms found in the intestines and other parts of the human body and the pathology and treatment of the various affections produced by their presence. the attitude was passive for many years.000 in 197514. lanceolatum and D. PACIFICUM The adult tapeworm. 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Diphyllobothrium ursi from man in British Columbia . 1602. Parasitic helminths and arthropods from Pinnepeda of the Canadian Pacific coast. ROMANOV IV. GUERRA H. NYBERG W.first report of this tapeworm in Canada. TARASSOW W. Säugetier. II. 1933 63. ALVAREZ H. partly translated in 42. 1968. ÖSTLING G. RAUSCH RL. The broad tapeworm in Minnesota with the report of an infection acquired in the state. Moscow. XLIV. Acta Medica Scandinavica 167: 185187. 1968. Basel. Studies on the helminth fauna of Alaska. In vivo studies with the Schilling test technique. 1887. DONCKASTER R. 1956 55. I.Diphyllobothriasis 417 Jena. pp 3-6. Journal of the American Medical Association 46: 711-713. Moscow. 1910 51. MAGATH TB.und Tropen-Hygiene 37: 307-315. 1931 59. Etudes sur l'origine des cestodes et leurs états larvaires. Recherches sur le développement des Cestodes. MARGOLIS L. 609. LAPSHINA IG. Partly translated in 42 71. The occurrence of Diphyllobothrium latum (Linnaeus. 1758)(Cestoda: Diphyllobothriidae) in Alaska. with notes on other species. The relation of Diphyllobothrium latum infestation to the public health. REYHER G. Acta Medica Scandinavica 167: 189-192. 1970 66. pp 679. 1982 52. Evacuation de quatre-vingt-dix bothriocéphales ou une seule fois. three volumes. 1931 54. Diaptomus graciloides (Lilljeborg). Tropenmedizin und Parasitologie 33: 5-7. NEGHME A. 1662 64. Bulletin de la Société Neuchâteloise des Sciences Naturelles 42: 29-49. Revista Médicade Chile 78: 410-411. I. 1960 60. Bulletin de la Société Neuchâteloise des Sciences Naturelles 43: 1-55. 1973 56. 1967. Archiv für Wissenschaft und praktische Tierheilkunde 53: 353-361. Journal of the Fisheries Research Board of Canada 13: 489-505. 1933 53. A golden practice of physick. SILVA R. 1960 61. "Diphyllobothriasis symposium". PETRUSCHEWSKY GK. Le cycle évolutif des Bothriocéphales. LUMBRERAS H. ein neuer erster Zwischenwirt von Dibothriocephalus latus. The influence of Diphyllobothrium latum on the vitamin B12-intrinsic factor complex. second edition. ESSEX HE. Journal of Preventive Medicine 5: 227-242. Abstracted in Tropical Diseases Bulletin 64: 993. In. 1950 57. Correspondenz-Blatt für schweizer Aertze 17: 488-491. Cited in 14 70. GUSEVA MK (Effectiveness of treatment of diphyllobothriasis with dichlosale and phenasale. ROSEN F. Journal of the American Medical Association 101: 337-341. HILLIARD DK. nebst Bemerkungen zur experimentellen Entwicklung des Procercoids dieses Cestoden. Journal of the American Medical Association 90: 673-678. 1944 85. Umhüllung von Flimmer-Epithelium bei den Embryonen von Bothryocephalus (sic) latus. pp 55. Lahr. von BONSDORFF B. Die parasitaren Krankheiten des Menschen. Zeitschrift für Parasitenkunde 13: 165-174. 1929 90. TARASSOW W. 1887. Annales de Parasitologie Humaine et Comparée 15: 524-528. (Cure of pernicious Biermer's anaemia by expulsion of Bothriocephalus latus. VERLOREN M C. On the pathogenesis of pernicious tapeworm anaemia. the broad tapeworm of man: experimental studies. TÖTTERMAN G. Das Schwein und der Hund als endgültige Träger des Diphyllobothrium latum. Diphyllobothrium latum (Linn 1758). Patavii. A case of Bothriocephalus latus infection. Acta Medica Scandinavica 173: 147-154. SCHUBART. VERGEER T. SCHUBART. TARASSOV V (TARRASOW W). 1963 80. 1934 86. pp 88. Stockholm. 1887 74. 1618 81. 1963 75. VERGEER T. SPIGELIUS A. La provenance des entozoaires de l'homme et leur évolution. The broad tapeworm in America with suggestions for its control. 1882 83. Journal of Infectious Diseases 44: 1-11. De lumbrico lato liber (cum ejusdem lumbrici icone et notis). H Georg.).418 A History of Human Helminthology Journal ii: 911. SAARNI M.) Vrach 8: 95-96. Abstracted in Lancet ii: 724. In Russian. Beråttelse om en Qvinna. De l'immunité envers le bothriocéphale Diphyllobothrium latum (L.und Tropen-Hygiene 38: 156-159. p 147. NYBERG W. Deutsches Archiv für klinische Medicin 41: 304-308. 1747 82. Genève. Suomen Lääkarilehti 18: 2359-2361. SOININEN V. Part 1. Journal of the American Medical Association 66: 1618-1619. This wormy world. Cited in 90 78. pp 52. RUNEBERG JW. Cited in 44 77. Conférence faite au Congrès international des sciences médicales à Genève. Symptoms in carriers of Diphyllobothrium latum and in uninfected controls. le 15 Septembre 1877. SINGER JJ. Leveän heisimadon esiintyminen ja joukkohääto Puumalassa. 1887 76. Secretary's abstract. Bihand till Kongliga Svenska Vetenscaps-Adakemiens Handlingar. SPÖRING HD. 1937 87. 8: 103-112. 1947 84. Amtliche Bericht über 33 Versammlung Deutschen Naturforscher und Aertze (1857). SCHAPIRO HA. 1859 91. 1928 89. Bothriocephalus latus und perniciöse Anämie. Archiv für Schiffs. 1916 79. 1887 73. Eine experimentelle Untersuchung. Journal of Parasitology 33: 1-18. hos hvilken et stycke af Binnike Masken kommit utur en bålde i liumskan. L Pasquati. 1976 88. GRASBECK R. Annals of Clinical Research Supplement 18: 1-48. STEIN ST. VOGT C. STOLL NR. SZIDAT L. 1878 . f. then produced patent infection with adult worms in dogs fed with plerocercoids 1882 Braun produced patent infections in humans who ingested plerocercoids 1877-86 Reyher found that pernicious anaemia was cured in patients who were also infected with D.Diphyllobothriasis 419 Table 15. latum eggs in these copepods. Various anthelmintics were used 1592 Dunus described tapeworms with morphological features now recognized as those of Diphyllobothrium 1602 Platter differentiated Diphyllobothrium from Taenia on the basis of the shape of the proglottids 1700 Andry described Diphyllobothrium as "Taenia à épine" to indicate the central "spine" due to the medially placed genital pores of Diphyllobothrium c. Landmarks in diphyllobothriasis ___________________________________________________________________ Tapeworm infections in humans were known but the species were not distinguished. even though the parasite persisted 1948 von Bonsdorff showed that tapeworms competed with the human host for dietary vitamin B12 1963 Soininen showed that niclosamide was effective therapy 1977 Praziquantel was introduced for treatment by various investigators __________________________________________________________________ BC . the lateral pores of Taenia 1747 Spöring drew attention to the relationship between broad tapeworm infection and human habitation near water with an increased consumption of fish 1777 Bonnet illustrated the head of the adult worm 1860 Davaine described diagnosis by finding eggs in the faeces 1881 Braun found larvae (plerocercoids) resembling Diphyllobothrium in pike. burbot and other fish. then obtained plerocercoids in fish by infecting them with procercoids 1928 Isaacs and colleagues treated successfully tapeworm pernicious anaemia by the administration of raw liver.1. observed the development of coracidia obtained from D. latum and in whom the worm was eradicated with anthelmintics 1883-86 Runeberg made observations similar to those of Reyher 1901 Hamilton reported a case which had been unequivocally acquired in North America 1917 Janicki found very young larvae of Diphyllobothrium (procercoids) in the stomach of fish which also contained many copepods and thought that copepods may be the primary intermediate host 1917 Rosen independently found procercoids in the body cavity of certain species of copepods. . fragments of worm were passed by an eight year old girl in Mauritius18. satyri. mucronata 9. Since that time. The first human infection was described in 1928 by Cram who studied specimens recovered from a young Spaniard by Dr Alberto Recio in Cuba25. sporadic cases of human infection have been reported from a number of regions of the world. B. The life cycle of B. particularly India and Indonesia. some being described as B. it was renamed Bertiella studeri by Stiles and Hassall in 1902105. including B. STUDERI This cyclophyllidean tapeworm was first recovered from an orang-utan (Pongo pygmaeus pygmaeus). but current opinion separates B. mucronata. Treatment with niclosamide was found to be successful29. B. MUCRONATA The adult tapeworm was first recovered from a howler monkey (Alouatta nigra) in Paraguay by Meyner in 189578. studeri. Some authorities have considered that these species are all synonymous with B. it has also been found in other subhuman primates and in dogs in the Philippines. then was described by Raphael Blanchard in 1891 as Bertia studeri (after Dr Paul Bert)15. Infection in a human was reported for the first time in 1913 by Blanchard. A number of other species of Bertiella have been described. Because this generic name was already occupied. Scheloribates laevigatus and Galumna species107. satyri . he showed that cysticercoids developed in the mites. polyordus and B. mucronata. studeri 1.Chapter 16 CESTODE INFECTIONS IMPORTANCE OF LESSER INFECTION WITH BERTIELLA SPECIES B. although he named the parasite B. Since that time. 421 . but the modern view is that they were probably B. studeri was described by Stunkard in 1940. A number of further cases have been reported from the Americas. The life cycle of the parasite was first investigated by Melnikov who showed in 1869 that when eggs were ingested by the dog louse. FUKUOKAENSIS In 1970. cucumerina by Bloch in 1782 19 Dipylidium cucumerinum by Leuckart in 186370 . infections with adult worms occur in humans. who could not infect these lice experimentally.422 A History of Human Helminthology INFECTION WITH DIPLOGONOPORUS SPECIES D. Pulex serraticeps (= Ctenocephalides canis). The generic name is derived from a combination (DIS) and (PYLIS) meaning "two" and "gate". respectively. the hexacanth embryos were liberated in the intestines then migrated to the body cavity where they tranformed into cysticercoids 77. then renamed Diplogonoporus grandis by Lühe in 189973. Kamo and his colleagues have shown experimentally that certain species of copepods act as the first intermediate host59. (GONOS) and (POROS). T. Recently. 10-70 cm long. in 1888. then Dipylidium caninum by Railliet in 189288. however. Trichodectes canis. By 1971. most patients have been Japanese. Sonsino. Although this was later disputed by Zimmerman122. GRANDIS This pseudophyllidean tapeworm. DIPYLIDIASIS A cyclophyllidean tapeworm of dogs and cats. the validity of this vector is generally accepted. Occasionally. The clinical features are similar to those seen in taeniasis. meaning "double". 55 cases had been reported in Japan. It was named Taenia osculis marginalibus oppositus by Linnaeus in 1748. Taenia canina by him in 175873. The generic name is derived from a combination of the Greek words (DIPLOOS). examined the possible role of fleas in transmission but convinced himself that the mouthparts of fleas were too small to allow ingestion of Dipylidium eggs100. of the Greek words respectively. was first described by R Blanchard in 1894 as Krabbea grandis 17. Grassi and Rovelli showed that eggs hatched in the intestines of the dog flea. The first such patient was described by Ijima and Kurimoto in 1894 on the basis of a specimen found in a 28 year old man by Nakamura in 189250. has been known for generations. The second intermediate host remains uncertain. The parasite was recovered from a girl in Japan60. "gonad" and "pore". which is normally a parasite of whales. and the . which presumably reflects their penchant for eating raw fish. D. Kamo and Miyakai described this worm as a new species. In the following year. then bite and swallow the vectors. diminuta by Blanchard in 189116. the parasite was not described until 1858 when Weinland named it T. USA. Dubois wrote: "est Taenia species quae. was re-examined by Leuckart who concurred with its identification as D. These results were confirmed by Joyeux56 who also demonstrated that the beetle. then migrated into the body cavity where they developed into procercoid then cysticercoid larvae43. Tenebrio molitor. Pulex irritans. caninum 70. and Ctenocephalides canis. Ceratophyllus (= Nosopsyllus) fasciatus. A number of other arthropods have since been shown to also act as intermediate hosts. Pulex irritans. varesina. Acis spinosa and Scannus striatus 44. Anislabis annulipes. The parasite was transferred to the genus Hymenolepis of Weinland (see next section) and named H. Joyeux then transferred these infections experimentally to rats that ingested infected arthropods. Grassi and Rovelli showed that cysticercoids developed in a moth. The third case was described by Joseph Leidy in the USA in 1884. The clinical manifestations are similar to those seen in taeniasis. as well as in its larval stage. Xenopsylla cheopis. this worm was sometimes referred to as T. when he found them in a 19 month old child. and niclosamide has been found to be an effective remedy55. Infections have since been reported sporadically from many parts of the world. It was named Taenia diminuta by Rudolphi in 181992. vulgarites in canibus et saepissime apud homines invenitur"31 meaning that this tapeworm was commonly found in dogs but rarely in humans. Italy87.. Salzmann of Esslingen then found the parasite in a 16 month old child in 186194. then deposited by Mekel in the Museum of Comparative Anatomy in Halle. they are all eaters of faeces or are scavengers during their larval or adult stages. A second case of human infection was reported by E Parona in 1882 as occurring in a two year old girl in Varese.Miscellaneous Cestode Infections 423 human flea. In 1892. Since then it has been reported sporadically from many parts of the world. a pupil of Linnaeus.. in the othopteran arthropod. HYMENOLEPIASIS HYMENOLEPIS DIMINUTA The cyclophyllidean adult worm.. and the larval stages of the fleas. most of the affected individuals being children. A second specimen recovered from a 13 year old boy in Blasius. flavopunctata 114. 20-60 cm long. The first human case of dipylidiasis was seen by in 1751 by Godefridus Dubois. and in the beetles. normally lives in the intestines of rats and mice. . The worms were recovered from a human for the first time in 1842 by Dr E Palmer of Boston. were also susceptible. They noted that the itch induced by these arthropods caused the dogs to paw and gnaw at the skin. Asopia farinalis. and the infection has been shown to respond to treatment with niclosamide 55. murina 16. nana and the genus Hymenolepis for T. nana were so similar morphologically. Weinland proposed dismembering the genus Taenia and established the genus Diplocanthus for T. The worm was a fully developed Taenia with broad segments. The generic name. Bilharz had provided some of his worms to museums in Vienna and Halle.13 Von Siebold duly reported this discovery in his journal. H. he sent the worms to Leuckart who recognized them as H.disclosed immediately large numbers of a small tapeworm. H. Stiles separated H. and renamed it Taenia (Hymenolepis) nana in 186370. it was the width of a sewing thread and length of hardly 10 mm. Meanwhile. NANA This tapeworm was discovered in 1851 by Theodor Bilharz during the autopsy of a boy in Egypt who had died from meningitis. who accepted the identity of T. Although Spooner may have found these worms in the USA in 1873101. is derived from a combination of the Greek words µ (HYMEN) and (LEPIS) meaning "membrane" and "shell". they were not met again with certainty until 1885 when Dr Hoelz in Belgrade recovered 50 small tapeworms from a seven month old girl after treatment with ethereal extract of male fern. murina because when he gave mature proglottids of T. and after noting that Bilharz had wanted to call it Taenia aegyptiaca in view of the country in which it was discovered and suggested that "it be named Taenia nana because this tapeworm differs by its smallness so greatly from the other two species of man"13. He wrote to his mentor. nana and T. describing his findings: The first incision into the intestine. and a murine variety. nana was merely a variety of T. had already been used by Agassiz for a genus of fish. nana var. nana infection was endemic in humans in that district. von Siebold. Hymenolepis.424 A History of Human Helminthology The clinical features are usually minimal.. so this name was invalid. and as the human and rodent forms appeared to have different geographical distributions. Joyeux (1919) again proposed to separate them into . however. nana 72. H. The name Diplocanthus. In 1858. In 1906. Since this worm and H. however. since H. Grassi (1887) was of the view that T. speciation was based upon the susceptibility of rats and humans to the strains of parasite derived from each species. in Germany. fraterna 103. Eventually. A similar parasite in rodents was described by Dujardin 1845 as Taenia murina 32 . however. This experiment proved little. respectively. Since repeated attempts to infect the heterologous host species were unsuccessful.. one individual developed a patent infection42. nana. it was designated Hymenolepis nana in 1891 by Blanchard. nana into a human variety. murina to six persons. Leuckart then used these specimens to improve the morphological description of the parasite. murina and related species114.. the cysticercoids differed morphologically somewhat from those developing directly in the intestine of the definitive host. On microscopical examination of the intestines of infected rodents. proglottid formation began on the eighth day and eggs were found in the faeces 16-17 days after infection. Uchimara and Kiribayashi then did the reverse experiment and infected children with Hymenolepis eggs from murine sources.Miscellaneous Cestode Infections 425 two distinct species. murina of Dujardin. When he tried again and infected a four year old girl. nana and H. nana and H. nana is now well-recognized as being widespread and common in children in certain parts of the world. fraterna (or T. Grassi in 1887 showed that transmission from rat to rat was direct without the mediation of a vector42. Tenebrio molitor and T. In all these vectors. The name. Saeki in 1920 showed that infection could occur across species. then after five days. but all his efforts to infect himself failed. Saeki examined the kinetics of infection in mice and also proved that humans could be infected directly93.500 adult worms. obscurus. In addition to this direct cycle. Saeki then swallowed 1. H. then infected successfully mice. fraterna. he found eggs in her faeces after 19 days. however. In 1920. These results were confirmed by 111 Uchimara111and Woodland117. worms could be found in the intestinal lumen. this nomenclature had been used by Gmelin in 1790 to describe the worm related to Cysticercus fasciolaris of Rudolphi (1808). however. cysticercoids were noted in the mucosa at four days. for Heynemann47 found that previously uninfected mice infected with as few as 10-25 larvae developed up to 1. and the mealworms. indicated that H. longior) and Woodland . He obtained Hymenolepis eggs from a nine year old girl. H. oncospheres were seen in the villi ten hours after infection.000 eggs himself on four occasions. the name Taenia nana had also been used by van Beneden in 185212 for a parasite that was subsequently identified as being the adult form of Echinococcus granulosus. Contrary to initial impressions. was chosen since the prior designation. then later Bacigalupo in Argentina demonstrated that the fleas. fraterna 57. Thus. To confuse the nomenclature even further. Xenopsylla cheopis and Ceratophyllus fasciatus 85. together with the morphological similarities. this was confirmed several decades 96 117 later by Joyeux56. Studies designed to elucidate the life cycle of both the murine and human forms of the parasite were pursued concurrently with attempts to define their host specificity. the . was invalid. It is possible that heavy infections are at times the result of autoinfection. H. rats and one out of two monkeys93. large numbers of adult worms were found. When she was treated 62 days after infection. Scott (as H. Nicholl and Minchin found the cysticercoids of the parasite in the body cavities of the fleas. Ctenocephalides canis and Pulex irritans. however. This was confirmed by Johnston54. murina) were identical.118 . were also capable of transmitting the infection5. T. In contrast to Joyeux's contention that there were two species. these results. birds and small mammals. This was changed to Raillietina madagascariensis by Joyeux and Baer in 192958. and "similar". Mepacrine was only moderately efficacious. M. In Africa. respectively. foxes and other mammals. The larval . Larvae are found in the body cavity and tissues of reptiles. In 1893. (KESTOS. Infected patients have been reported from Africa and Central and South America. In 1891. and the infection has been observed to respond to treatment with niclosamide 48. LINEATUS The cyclophyllidean adult tapeworm is normally a parasite of dogs. then finally it was classified as Inermicapsifer madagascariensis by Baer in 19566. INFECTION WITH INERMICAPSIFER MADAGASCARIENSIS This cyclophyllidean tapeworm was first described by Davaine in 1870 as Taenia madagascariensis 27. respectively. Adult worms rarely infect humans. The specimen had been recovered from an 18 month old child in the Comoros Islands in the Indian Ocean by Grennert in that year. VARIABILIS The adult worm is normally a parasite of the intestinal tract of foxes. rodents were found to the major definitive host. "case" and "to carry". It was first described by Mueller in 192881. meaning "unarmed". Blanchard renamed the worm Davainea madagascariensis 15. even when parasites are present in large numbers. The generic name is derived from a combination of the Latin words "inermis". "tape". Railliet89 transferred it to the genus Mesocestoides that had been erected by Vaillant in 1863112. but then niclosamide was shown to be partially effective11 and praziquantel was then found to be even better95. cats. Most patients have been reported from Japan. It was first described as Taenia lineata by Goeze in 1782 41. The generic name is derived from a (MESOS). the first patient being described in 1942 by Kosaka65. The early anthelmintics were generally ineffective63. "capsa" and "fero". combination of the Greek words µ CESTOS) and (EIDOS) meaning "middle". INFECTION WITH MESOCESTOIDES SPECIES M. The life cycle has not yet been elucidated. skunks and similar mammals. The clinical features resemble those seen in taeniasis. Treatment at first was difficult. but elsewhere is appears to be a parasite of humans only6.426 A History of Human Helminthology infection has usually been found to be asymptomatic. the adult worm is a common parasite of rats. Rats (or humans) acquire infection by ingesting infected ants. In 1891. recorded by Chandler in 1942. Leuckart described a worm recovered from an infant in Bangkok as Taenia madagascariensis 71. Human infections. and worms up to 40 cm long develop in the intestines. demerariensis by Dollfus in 1939-1940 30. In 1964. this was probably R. In 1920. celebensis. as was the infection found in an adult in Manila and described as Davainea madagascariensis by Garrison in 191138. CELEBENSIS This cyclophyllidean tapeworm was first found in the long-tailed mouse.Miscellaneous Cestode Infections 427 stages are found in a wide variety of carnivorous animals. The clinical manifestations are usually minimal and the infection was found to respond to treatment with niclosamide. Subsequently. have been reported from Asia and the Pacific. Adult worms are found rarely in humans. mostly in young children. patients were reported from Denmark (in a Greenlander). and described by Janicki in 1902 as Davainea celebensis (the genus being named in honour of Casimir Davaine)52. Infections have since been seen frequently in parts of South America. Tang and Tang showed that the intermediate host is ants of the genus Cardiocondyle. DEMERARIENSIS The adult tapeworm. Akashi in Taiwan again recorded infection with the parasite. adult ants carry proglottids to the nest and feed them to the young ants in which the cysticercoids develop109. especially in Ecuador. these segments were thought to represent at least four worms22. was first found by CW Daniels in Demerara. The first case. was of a 13 month old child in Texas who passed more than 25 feet of tapeworm segments when treated with oleoresin of aspidium. In these regions. R. this time naming it Davainea formosana 2. British Guiana (now Guyana) in 1895. about 60 cm in length. In 1916. but all were recognized as R. A number of other names were then used. Lenomys myeri. INFECTION WITH RAILLIETINA SPECIES R. he named it Taenia demerariensis 26. Fuhrmann transferred the worm to the genus Raillietina (named in honour of Professor A Railliet)37. . from East Africa (in a European) and from the USA. similar worms in the pleural cavity. he discovered a dozen ribbon-like worms 30 cm long by 5 mm wide in the retroperitoneal adipose tissue. The worm was renamed Bothriocephalus liguloides by Leuckart in 1884 then Bothriocephalus mansoni by Blanchard in 1886.SPARGANOSIS In 1881. Yamada. diphyllobothriids). including Manson himself. to house worms with similar morphological features. Although this genus could not stand with the acceptance of the theory of alternation of generations and the recognition that these worms were immature. and large numbers of parasites in the gastrointestinal tract75. the investigators recovered a single. different eggs began to appear in the faeces. Patrick Manson in Amoy. The complete natural life cycle was then elucidated by Okumura in Japan in 191986. possibly related to Diphyllobothrium. Diesing28 had raised the genus Sparganum. believed that these worms were an immature form of cestode. the name being derived from the Greek word (SPARGANOS) meaning "ribbon". In June 1916. Thirteen days later. Post-mortem examinations were extremely difficult to carry out as the populace was opposed to them and a previous attempt by Manson to perform one had had unfortunate consequences. discovered by Manson. then recovered procercoids as had been shown two . When the dog was killed two months after infection. Yoshida and his collaborator. This had. adult tapeworm which they took to be a Dibothriocephalus (= Diphyllobothrium)119. In 1854.428 A History of Human Helminthology INFECTION WITH SPIROMETRA SPECIES (1) HUMANS AS THE INTERMEDIATE HOST . fed a Sparganum removed from the abdominal wall of a female patient to a dog that was coincidentally infected with Diphyllobothrium cordatum. was in quest of an adult filarial worm (Wuchereria bancrofti) in order to support his view that elephantiasis was a consequence of an infection with this worm (see chapter 23). He took ova from these worms and infected Cyclops leuckarti. He sent these specimens to Spencer Cobbold in London who believed them "to be new to science" and named them Ligula mansoni . China. lymph-scrotum and dysentery died in September of that year.76. He found adult tapeworms in naturally-infected dogs that were identical with those raised by Yamada and Yoshida. large. Manson carried out a secret autopsy with the aid of a trusted servant in the Chinese cemetery at the dead of night by the light of a flickering candle. whose adult state was unknown.e. When a 34 year old man with elephantiasis. Instead of finding adult filariae. A number of workers. in fact. already been done by Stiles and Tayler-Jones106 who in 1902 called the parasite. pseudophyllidean. Sparganum mansoni. Verdun in 1907 suggested that each immature form of the "Bothriocephaliden" (i. should be placed provisionally in this genus until the adult form was ascertained. this name was noted by the editor of The Lancet 3 in an addendum to Manson's report. the formal description by Cobbold following the next year23. Faust pointed out that although the term Sparganum mansoni had been used for all the unbranched spargana recovered from man. had extracted spargana from the fingers of two patients who had applied split frog poultices to themselves. Casaux presented. to the Indochinese MedicoChirurgical Society. In May 1927. he found spargana in chickens and ducks and concluded that humans acquire infection either by drinking water containing infected Cyclops or from eating raw. and by direct penetration of plerocercoids from poultices through the skin. By these means. Evanno arrived at the same conclusion. By the early . particularly in patients in Indochina. inoculated themselves subcutaneously. then excised some of the parasites ten or more weeks later. Mueller and Coulston84 carried this experiment one stage further. and which could only be identified after generation of the adult form in experimental dogs35. such a case and recounted that the woman had been in the habit of applying dismembered frogs to her eyes. contaminated chicken120. Independently. The possibility of being infected in such a way was confirmed by Kobayashi64 who infected himself percutaneously. Further. When plerocercoids from these naturally infected animals were in turn fed to dogs. all of which had an identical appearance in the sparganum stage. and transferred one of them to a cat where it was able to continue its natural evolution. it was determined that infection could be acquired in one of three ways . he declared that the larvae should be referred to as the larval stage of the appropriate adult worm. Okumura showed that similar parasites were to be found in 30-60% of frogs in that region of Japan. there were several species. of hard. Faust and his colleagues35 noted that AS Campbell of Foochow.Miscellaneous Cestode Infections 429 years earlier for Diphyllobothrium latum (see chapter 15). then excision of the skin revealed three plerocercoids in tunnels in the dermis and hypodermis. he suggested that there may be direct entry of spargana into the orbital tissues. Two further excisions. similar adult tapeworms developed in the intestines. Both of these experiences are recorded by Motais80 who also reported four similar cases in which ocular sparganosis again followed application of split frogs to the eyes. thus Sparganum mansoni indicated the sparganum stage of Diphyllobothrium mansoni. the second 47 days after infection. In 1922. Moreover. Elaphe climacophora. migrate into the body cavity of these hosts. by ingestion of contaminated flesh (plerocercoids). rounded. China. painless. he placed a sparganum in the conjunctival sac of a monkey and recovered it 11 days later from the upper lid. In 1929. Furthermore. Penetration of the larvae caused itching and erythema. Sparganosis was prone to afflict the eye. Yoshida showed that as well as being host to adult worms. and develop into plerocercoids or spargana. as well as in the snake. The procercoids were then fed to experimental frogs and mice and were found to pierce the intestinal wall. subcutaneous nodules disclosed more plerocercoids.by drinking infected water (procercoids). They obtained spargana from a monkey. cats and dogs also harboured the larval stages. The sparganum is peculiar in that it proliferates or multiplies by forming branches which become detached. mansoni was the dominant species. decipiens. In 1935. He claimed excellent result in 12 patients treated with a course of intravenous injection of novarsenobenzol 62.430 A History of Human Helminthology 1930's. The usual treatment today. however. The adult form of this sparganum is still unknown. patients usually presented with a subcutaneous nodule which may or may not have migrated and which may or may not have become inflamed. ranarum and D. thousands of spargana have been recovered from their tissues10. The place of praziquantel has not yet been established. (2) HUMANS AS THE DEFINITIVE HOST . a sparganum stage in mice. He named the parasite Plerocercoides prolifer 49. D. Spirometra 83. D. In Vietnam. for example. the injection of 40% ethanol into the worm was recommended by Cornet24. Keller. most spargana were found in the subcutaneous tissues. and the latter was often complicated by ophthalmia which necessitated removal of the eye.SPIROMETROSIS S. leuckarti and other species of Cyclops. where S. Several years later. although they have been recorded from the brain and viscera as well. believed that all these forms could be found in different parts of the one strobila. In Asia. however. Neither this therapy nor surgical excision was favoured by the director of the Ophthalmic Institute in Hanoi. is surgical excision with antibiotic cover. Most of the few patients reported have resided in Japan. Reports of human infection from many parts of the world allowed a picture of the clinical features to be built up. but of a new species which had a procercoid stage in C. mansoni. reptans. The most usual treatment has been by surgical excision which also allows the diagnosis to be made.D. When located superficially. There were dissenters. where ocular sparganosis was common. and to a lesser degree in dogs82. and thus recognized only one species. This worm he named D. who had experience of 60 cases. because the former frequently did not work. Iwata51. okumari. houghtoni The adult form of this pseudophyllidean tapeworm was first recovered from a . if necessary. and a definitive stage in cats and bobcats. In the Americas where S. D. The balance of opinion has swung against his view. erinacei. A different form of Sparganum was reported by Ijima in 1905. mansonoides was the most frequent species. then this was reclassified as Sparganum proliferum by Stiles in 1908104. Mueller showed that those spargana found in North America were in fact not the larval stage of D. D. they often caused recurrent attacks of inflammation. mansonoides. six other species were recognized . houghtoni. Mueller partitioned the genus Diphyllobothrium and transferred all of the worms mentioned into a new genus. The clinical features are usually those of a space-occupying lesion. recorded. Finally. serialis.Miscellaneous Cestode Infections 431 patient in Shanghai by Dr HS Houghton and described as D. so the human cases in that region are probably caused by the larval form of T. the first such patient being reported by Fain and colleagues in 195633. each in its own separate and inverted canal. or in the eye. brauni may cause the African form of coenurosis. In the Western hemisphere. mansoni by Faust and Wassell in 192136. The effectiveness of praziquantel . Diagnosis and treatment both depend upon surgical excision. human infection. the coenurus was fed to a dog and seven characteristic scolices were obtained. however. in a Paris locksmith who presented with convulsions and aphasia. Coenuri are characterized as bladder worms with multiple scolices. Similar coenuri had been noted previously in gerbils by Railliet and Henry90. houghtoni in 192935. In human infections. T. in the connective tissues of the muscles or subcutaneous tissues. Turner and Leiper in 1919. one being degenerate and the other containing 75 scolices21. multiceps) were found in the brain. unless the adult worm is generated by feeding experiments. serialis was reported in a 59 year old Frenchwoman by Bonnal and colleagues in 193320. then renamed Sparganum erinacei-europaei by Diesing in 185428. The first authentic. the first such infection reported was in 1950 of a two year old Californian boy with cerebral coenurosis53. serialis. erinacei This tapeworm was first recovered from a hedgehog (Erinacea europaea) and described as Dobium erinacei-europaei by Rudolphi in 181992. Most of the infections reported subsequently have been in the brain. reported a human infection in Nigeria with a coenurus which they called Coenurus glomerulatus 110. all in Japan108. was described by Brumpt in 1913. then called Diphyllobothrium erinacei by Faust and colleagues in 192935. brauni or T. multiceps has been absent for many years. it is often impossible to tell which species is the causative organism. S. It has been recorded as a parasite of man in five cases. INFECTION WITH TAENIA SPECIES (1) HUMANS AS THE INTERMEDIATE HOST . T. Faust and his colleagues renamed this worm as D. it was transferred to the genus Spirometra by Mueller in 193783.COENUROSIS Coenurosis is an infection with the larval stages of one of several tapeworms. At autopsy. the adult form and the definitive host are unknown and the worm is possibly identical with T. The first proven case of human coenurosis due to T. two coenuri (probably T. especially sheep. following Stiles and Stevenson. multiceps. Cysticercus longicollis. Some authorities have considered this species to be synonymous with T. serialis. According to Küchenmeister and Zurn. The larval stage. The cystic form was then renamed Coenurus cerebralis by Rudolphi in 180891.432 A History of Human Helminthology in the management of human coenurosis is not yet established. wolves and foxes. cerebrina. Finally. a parasite of dogs. T. In 1780. serialis The adult worm. T. T. (2) HUMAN INFECTIONS WITH INTERMEDIATE FORMS OF OTHER TAENIA SPECIES T. is found in small rodents and . then designated T. Wepfer stated that "gid" or vertigo in sheep and cattle was caused by a bladder in their brain and referred to an 69 40 epidemic which occurred in 1658115. Versteer transferred the worm back to the genus Taenia 113. Leske then Goeze independently discovered the scolices with four suckers and a double row of hooks in the bladders of this parasite. which was common in herbivores. in 1967. In 1910. It was transiently known as Multiceps serialis. Some authorities have considered this species to be synonymous with T. crassiceps The adult worm is a parasite of foxes. was described as Coenurus serialis by 7 Gervais in 184739. It was described as Alyselminthus crassiceps by Zeder in 1800121. cerebralis. multiceps 67. Scultetten and Rentter in 1634-1645 were the first to refer to the bladder-worm stage of this parasite97. Küchenmeister showed that C. with the former author naming it Taenia multiceps (multiceps meaning many-headed) and the latter calling it Taenia vesicularis. then this was confirmed by Haubner46. was the intermediate stage of T. Hall erected the genus Multiceps and transferred the parasite to it. It was given its current name of T. The larval stage of the parasite is found in horses. the worm's name thus becoming Multiceps multiceps 45. cystic worm in the brain). multiceps The adult worm is a parasite of dogs. goats and cattle. brauni The adult worm was recovered from the intestines of a dog in northeast Africa and described by Setti in 189798. serialis by Baillet in 1863 . In 1853. brauni by Fain and colleagues in 195633. multiceps (meaning the many-headed. then renamed Taenia crassiceps by Rudolphi in 181091. 1882 4. a tapeworm parasite of man and rodents. Recherches sur un cystique polycéphale du lapin et sur le ver qui résulté de sa transformation dans l'intestin du chien. 1916. T. It was finally designated T. 1917 3. taeniaeformis by Wolffhügel in 1911116. it was long known as C. Sobre una nueva especie de Taenia. Überhaupt und ihrer Arten . ADAMS AR. Xenopsylla cheopis Rothschild et Ctenocephalides canis Curtis. Naturgeschichte der Bandwürmgattung. 167. The taxonomic position of Taenia madagascariensis Davaine 1870. in both cases. BAER JG. Two further cases of human infestation with Bertiella studeri (Blanchard. The first case was described by Bacigalupo in 1922 as T. taeniaeformis The adult worm is a common parasite of cats. (3). Annals of Tropical Medicine and Parasitology 27: 471-475. Two infections in humans have been recorded. All the patients were Japanese. BACIGALUPO J. Annals of Tropical Medicine and Parasitology 50: 152-156. Its metamorphosis into an adult Taenia was first observed by Küchenmeister in 185266. BAILLET C. then renamed Taenia crassicollis by Rudolphi in 181091. Évolution de l'Hymenolepis fraterna Stiles. 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Cobbold. 1911 86. 1923 97. Entozoorum synopsis cui accedunt mantissima duplex et indices locupletissima. American Journal of Tropical Medicine 21: 399-425. Ueber das Vorkommen der taenia cucumerina in Menschen. 1919 87. PARONA E. American Journal of Medical Sciences 65: 136. RIVADENEIRA A. CABRERA G. SALZMANN. Science 16: 434. pp 104. Nuovi elminte dell'Eritrea. 238. Kitasato Archives of Experimental Medicine 3: 190-197. pp 43-47. three volumes. Naturkunde in Württemberg 17: 102. 1892 89. in the mouse. RUDOLPHI CA. SCOTT HH. ASALGADO N. pp 1370. Paris. 1977 96. Journal of Parasitology 49: 294-296. SCULTETTEN. Jahrescheft des Vereins für Vaterland. 1891. Specimens of Taenia nana. HENRY A. GALDAMES M. pp 811. Journal of Helminthology 1: 193-196. 1889 101. RUDOLPHI CA. 1908 105. 1808-1810 92. 1882 88. Sur un cénure de la gerbille à pieds velus. (Experimental studies on the development of Hymenolepis nana. Bolletino dei Musea di Zoologia e Anatomia Comparata della Real Universita di Genova. 1976 103. 1935). 1893 90. 1906 104. Notices parasitologiques. STILES CW. 1920. WALTERS J. pp 736. 1922. STERBA J. MUELLER JF. United States Public Health and Marine Hospital Service. Two species of cysticercoids from the rat flea (Ceratophyllos fasciatus). Paris. First record of Strobilocercus fasciolaris (Taeniidae-larvae) in man. Treuttel et Würtz. SPOONER EA. 1888. Transactions of the American Academy of Ophthalmology and Otorhinolaryngology 77: 778-783. MINCHIN EA. Pisa. 1873 102. MORALES E. Intraocular Taenia crassiceps (Cestoda). 1941 85. and Hymenolepis longior Baylis. pp 7-18. Bulletin de la Société Zoologique de France 17: 110-117. Bertiella. 1861 95. Di un caso di Taenia flavopunctata riscontrata in una bambina di Varese. A contribution to the experimental study of the life histories of Hymenolepis fraterna Stiles. A repartition of the genus Diphyllobothrium. OKUMURA T. 1935 83. 1902 106. 1897 99. HOFFMAN MT. Proceedings of the Zoological Society of London 1: 9-13. 1921 94. SHEA M. A larval cestode (Sparganum mansoni) of man which may possibly occur in returning American troops. Also. Atti della Società Toscana di Scienze Naturali Residente in Pisa 10: 20-64. Giornale dell'Accademia di Medicina di Torino 32: 99. pp 203-244. pp 47. Bulletins de la Société de Pathologie Exotique et de ses Filiales 8: 173-177. MUELLER JF. HASSALL A. STILES CW. United States Public Health and Marine Hospitals Service. An experimental study on the life-history of Sparganum mansoni. Folia Parasitologica 23: 221-226. United States Department of Agriculture. RENNTNER. MABERLEY AL. second edition. Boletín Chileno de Parasitología 32: 11-13. The occurrence of a proliferating cestode larva (Sparganum proliferum) in man in Florida. A preliminary report. pp 56. Bulletin 35 of the Bureau of Animal Industry. a new name for the cestode genus Bertia Blanchard. In Japanese. HOSOGI H. 1929. Metcalfe and Co. Transactions of the Royal Society of Tropical Medicine and Hygiene 13: 23-24. 1969 114. YOSHIDA S. cum excertitatione de ejus loco affecto. WOODLAND WN.) Jikwa Zasshi No. 1922. YOSHIDA S. In Japanese. 1919 111. 1924 118.) Tokyo Iji-Shinshi Nos. "H. ex cadaveribus eorum. epidemiology and taxonomy. Raillietina (R. UCHIMARA R. A taxonomic revision of the genus Taenia Linnaeus. with remarks on "H. Acta Parasitologica Sinica 1: 1-13. 1964 110. 1800 122. 1858 115. An essay on tapeworms of man etc. pp 320. STUNKARD HW. On the life-cycle of the Hymenolepis fraterna (H. ZIMMERMAN HR. 1911 117. with especial reference to its development.) celebensis (Janicki 1902). Cambridge. Human cestoides. In Japanese. diminuta".. pp 108. Journal of Parasitology 3: 171-176. VERSTEER A. Institut. Bertiella studeri. Parasitology 16: 424-435. 1924 119. fraterna". 1922.438 A History of Human Helminthology 107. 1917 120. Erster Nachtrag zur Naturgeschichte der Eingeweidewürmer von JAE Goeze mit Zusätzen und Anmerkungen herausgegeben von Zeder. Scaffhusii. pp 93. KUMAZAWA H. its development in intermediate host. quos sustulit apoplexia. fraterna Stiles) of the white mouse. JC Suteri. pp 304. longior" and "H. (On the morphology of the adult form of Sparganum mansoni found in the frog and other animals. WEINLAND DF. VAILLANT L. The morphology and life history of the cestode. American Journal of Tropical Medicine 20: 305-333. TANG CC. TANG CT. 1923 121. A case of human infection with the adult of Spirometra erinacei (Rudolphi 1819). Siegfried Lebrecht Crusius. WEPFERUS JJ. The occurrence of Bothriocephalus liguloides Leuckart. WOLFFHÜGELK. Sur deux helminthes cestoïdes de la genette. LEIPER RT. (On the development of Hymenolepis nana and Hymenolepis murina. Massachussetts. 1758. NAKAGAWA O. str. 1982 109. Los zooparásitos de los animales domésticos en la República Argentina. ZEDER JG.. SUZUKI N. Zeitschrift für Parasitenkunde 9: 717-729. Faust. Observationes anatomicae. Campbell and Kellogg. s. Leipzig. Parasitology 16: 69-83. Japanese Journal of Parasitology 31: 23-26. 1940 108. nana var. WOODLAND WN. 286. Onderstepoort Journal of Veterinary Research 36: 3-58. Paris 31: 87-88. 1923 112. Life-history studies on cestodes of the genus Dipylidium from the dog. On the occurrence of Coenurus glomerulatus in man in West Africa. Buenos Aires. 1658 116. Abstracted in Tropical Diseases Bulletin 20: 223. Abstracted in Japan Medical World 3: 53. 1863 113. 1937 . 2271 and 2272. On the development of the human Hymenolepis nana (Siebold 1852) in the white mouse. TURNER M. each egg in the small intestine hatches a larva which passes to the caecal region and matures over 2-4 weeks Definitive host: humans Major clinical feature: pruritus ani Diagnosis: finding of eggs on a swab taken with sticky tape from the perianal skin Treatment: mebendazole. 26) mentions the occurrence of the worm in children 43. the Arab. When ova are ingested. the "thin ones". while Aristotle (384-c. Coulet in 1729 failed to distinguish well between E.320 BC) liste d among the three kinds of helminths of which he was aware: those which were large and flat. for example. described them 4. vermicularis and cucurbitini and gave the impression that a tapeworm consisted of a large number of E. the last mentioned worms. which he called ascaris. Hippocrates (c.1550 BC) as indicating this parasite 70. and deposit eggs on the perianal skin. Thus. 2-5 mm in length. Galen (129-c.independent motility. pyrantel. It is. Some authorities have interpreted the worm described as "Herxetef" in the Egyptian Papyrus Ebers (c. Avicenna (Ibn Sina). Similarly. viprynium AWARENESS OF THE ADULT WORM The adult form of the helminth now called Enterobius vermicularis was one of the few worms known to ancient man. The fertilized female worms. piperazine. for it wa s both big enough to be seen and had that incontrovertible sign of life . those which were cylindrical.200 AD) numbered the pinworm amongst the three species of human helminths he recognized 31. The nature and distinctiveness of this worm was not always understood clearly. the Roman. Knowledge of these worms continu ed down through the ages. and those which were thin 2.460-375 BC) in his Aphorisms (III. tha t represent the worms now named E. pinworm Major synonyms: Ascaris vermicularis. however. crawl out of the rectum at night. St. verm439 .Chapter 17 Enterobius vermicularis and ENTEROBIASIS SYNOPSIS Common names: threadworm. Records of it s existence may be found in the literature of several millenia go. whereas the "cylindrica l ones" are now designated Ascaris lumbricoides. With respect to the Greeks . Oxyuris vermicularis Distribution: worldwide Life cycle: The adult worms live in the region of the caecum. vermicularis. In 1758 in his Systema Naturae. 1758 on the grounds of page p reference (and that Ascaris lumbricoides should be given a different generic name). derived from a combination of the Greek words (ENTERON) and (BIOS) meaning "intestine" and "life". however. He confirmed this observation when analysing further samples sent b y Soemmering and by Hermann. naming it Ascaris vermicularis 60. Bremser ha d found. with the tail in the male worm being blunter and having a small spiculum. a number of species of worms which he placed in this genus. and that the termination of the tail in the two sexes were completely different. Earlier. h e recognized that whereas ascarids always tapered towards the two extremities and had three papillae at the anter ior end. oxyurids terminated by a point at one end (especially in the female) and lacked the three papillae. believing that the structure of the cuticle of this worm was different from that of other nematodes. In 1819. Johann Bremser 10 transferred the human pinworm to the genus Oxyuris which had been erected by Rudolphi in 1803 72 for certain parasites of animals. He deduced that male pinworms from humans ought to have similar characteristics. This led him t o conclude: The result of these observations is that the worms known under the name of Ascaris vermicularis henceforth ought to be classed in the genus oxyuris and not in the genus ascaris. Soemmering sent him a small jar full of oxyurid s preserved in wine. These worms had been passed by his own son after having taken an olive oil enema. Contoli. Dr. This name o f Enterobius vermicularis was accepted eventually. Bremser found undoubted male worms. In 1853. and transferred this worm to it. Similarly.10 Even more importantly. regarded the creature as a minute eel 21. After careful study. Eventually. Bremser wrote: "The sexes of thes e oxyurids can be distinguished by the characteristics that we have reported" 10. respectively. Thus. but initially. Linnaeus classified the organism among the Vermes. He was then struck by the similarity between these worms and the worms found in the rectum of humans.440 A History of Human Helminthology icularis connected together22. he noted that the male worms were one half to two thirds the size of the females. Bremser distinguished clearly between the male and female forms. amo ng them. By the end of th e eighteenth century a number of helmint hologists including Goeze and Rudolphi . In his observations of oxyurids of animals. ELUCIDATION OF THE MODE OF TRANSMISSION The origin of threadworms was shrouded in mystery and for most of recorded history was generally ascribed to spontaneous generation. Leach56 erected the genus Enterobius. in the large intestine of rabbits. he could not find any such examples in the specimens he had at his disposal . although Leiper 57 was later to argue unsuccessfully that it should be called Ascaris vermicularis Linnaeus. or of several children together. As late as 1855. ther e was not an instantaneous acceptance of th e idea that the adult worms developed from the eggs. one of which is troubled with Oxyurides is sufficient to infect whole families with these worms. the perpetual infection is established in consequence of the abundant reproduction of this parasite. Worms that were similar in appearance except in col our were found in the water of a nearby well and he concluded that they may have been the source of the affliction. they were ripe and in th e . Presumably. thought it inconceivable that they could be transmitted through th e media of food. Thus.. yet after that time. the sleeping of these parents and their children. children. For if only a single female which emigrated at night. which is expecially the case amongst the poor who only possess one bed. as to how transmission might occur.Enterobiasis 441 had found and described eggs within the female worms. has wandered into the intestine of one of these bedfellows who had hitherto been free from Oxyurides. whereupon eggs wer e released which in turn developed into adult worms: the emigration of a single pregnant female is sufficient to explain the infection of whole families with Oxyurides. Several years earlier (1812)..The sleeping of a married couple. in the same bed. wandered about th e bedding. Friedrich Küchenmeister was quite astray in his under standing of the life cycle of these worms. Twenty years earlier. Several years later. Nevertheless. This led him to deduce that development must take place within the warm milieu of an animal body. In 1860. albeit a fallacious one. who readily saw the eggs in femal e worms. a patient had come to him seeking removal of the threadworms which he. his wife. he was looking at either unfertilized eggs or ova which ha d degenerated in the water in wh ich he placed them. He saw no difficulty with the concept that minute germs might be imbibed in food or water then grow and develop within the human body and described an incident which he felt supported his belief. let alone the formation of a mature embryo. JM Barry in Ireland rejecte d spontaneous generation and proffered his own explanation.. one of whom is affected with Oxyurides. could discern no trace of segmentation. Claparède discovered that the most advanced eggs sometimes containe d tadpole shaped embryos whilst still within the body of the pregnant femal e worm17. then entered the gut of a bed-fellow (though whether he thought that this was via the mouth or the anus he did not say). He had kept ova in water for si x months. servant and visitors had all bee n afflicted with since moving to a new house four years before. He saw in the interior of each egg two large hyaline globules surrounded by finely granular detritus . he postulated that they crawled out of the anus at night. in 1858.55 Küchenmeister was in fact most unlucky with the Enterobius eggs he chose to study and the way in which he dealt with them. Vix reported that he had seen such eggs in the rectal mucus and had recovered them from the perianal skin. air or water and still clung to the theory of spontaneou s generation10. despite the objections of a naturalist acquaintance that the creatures were likely to be of a different species 5. Küchenmeister the n suggested that infection might be transmitted by the adult worms themselves. Bremser (1819). they continued to be passed in each stool for over a month 36. Some uncertainty remained. The role of mal e worms in the generation of these eggs had been a matter of controversy fo r many years. . however . The only way in which the question as to whether mature eggs could develop directly when ingested by a human. she found that those ova which contained embryos liberated them in the gastri c juice but that the larvae were killed by duodenal. three of the investigators found some young adult E. A similar experiment was repeated by Grassi in 1879. After noting that it was generall y supposed that the egg may be reared to an adult in the one and same bearer. however. vermicularis 6-7 mm long in their faeces. he became troubled by pruritus ani and he found a number of femal e worms full of eggs in his faeces. could be resolved was by experiment. then he ingested six femal e worms taken from an individual who had died 24 hours previously. In October. He first assured himself that h e was free from infection with E. of course. Wundt several years later collected eggs from the appendix and was unable to stimulate hatching of eggs with granular contents under any experimental conditions. was very similar to the one already propagated by Küchenmeister. he remarked (perhaps having the precedents of intermediate hosts for trematodes and cestodes in mind): "I believe this notion to be entirely fallacious" 18. Nearly two weeks later. as to whether adult worms coul d develop directly from eggs laid within the human body. or whether they first had to pass through an intermediate hosts. On the other hand. jejunal or appendiceal fluid. There was therefore no longer any reason to doubt that bot h male and female worms were involved in the reproductive process. In 1922. Thus. Zenker (1868) proved that it was easy to find many male worms at autopsy by scraping lightly the mucosal surface of the intestinal canal after removal o f faecal matter92. This view. Many years later. Leuckart himself recovered 18-20 worms over four weeks 59. there was no question that an intermediate host was quite unnecessary or that humans became infected by ingesting mature eggs. 1865 . however. vermicularis. Moreover. As men tioned earlier. Rudolf Leuckart and three of his students each swallowed a few dozen egg s which had been kept in a humified incubator. Bremser at first could not find any male threadworms in humans and speculated that reproduction might occur by parthenogenesis. the apparent rarity of this sex encouraged some authors such as Rudolphi and von Siebold to believe that this hypothesis may well be true. After fifteen days. This led him to surmise that young Enterobius were capable of developing directly in the r ectum without having to have a freeliving phase of existence 85. Goebe l claimed that he had succeeded in observing the development of ova that ha d been deposited in the intestine into mature worms in the lowest parts of th e small intestine and in the appendix 33. Spencer Cobbold writing in 1864 was little more enlightened than either of the previously mentioned investigators. Despite the eventual discovery of the male sex.442 A History of Human Helminthology process of hatching. A different means of retrograde infection was proven experimentally by Schüffner an d Swellengrebel. then amplified a few years later by Zenker. France and Italy that these worms resided not in the rectum but in the distal parts of the small intestine and in the caecum. He showed that when eggs were swallowed. observe such a phenomenon happening naturally 51. and took elaborate precautions to prevent infect ion by mouth. undergoing development in the external environment. This became the accepted dogma until th e middle of the ninteenth century although there were occasional remarks tha t worms could be found in the colon and especially in the caecum 46. He injected adult female worms into the rectum of a child be means of an enema.89. Germany. The placement of threadworms in the rectum seeme d eminently reasonable since many practitioners were familar with their habit of crawling out of the anus at night. then entering again b y the mouth91. Enterobius was thought to be localized chiefly in the rectum near the anus whereas Ascaris lumbricoides was assigned to the upper smal l intestine and tapeworms were deemed to extend over a considerable length of the small bowel. then migrate back through the anus and develop into adult worms.Enterobiasis 443 This led her to conclude that it was highly improbable that E. LOCALIZATION OF THE HABITAT OF THE WORMS Some of the ancient writers such as Galen 31 were able to differentiate the parts of the intestinal tract in whic h the three commonly recognized intestinal worms were located. Dr Gros of Moscow . In the middle of the nineteenth century. however. Koch did not. The child became infected and Koch concluded that worms multiplied in the intestine without externa l reinfection involving passage through the stomach. Zenker examined in detail the mode of development of worms following the ingestion of eggs. publicized this finding 37. a process which they called "retrofection" 80. This conclusion was reinforced by the finding of Philpot wh o showed that the "tadpole" larva was destroyed by digestive juices whereas a later stage of the parasite. becam e resistant to those juices 68. the embryo s hatched in the stomach. having ascertained on the basis of autopsy studies in Russia. Worms i n all stages of development were . They showed that larvae could hatch on the perianal skin. which had developed an oesophagus. This observation was confirmed shortly thereafter by Stricke r in Frankfurt 84. then passed into the upper small intestine where they increased rapidly in size and moulted. Koch in 1925 then investigated the hypothesis put forward that adult worms might re-enter the anus and produce infection by that means. vermicularis could develop within the gut without the eggs first passing out in the faeces . however . How important this mode of infection is in nature remains uncertain. 28 The accuracy of Hippocrates' appreciation. The number of worms in the bowel is extremely variable. attent ion turned to determining whether a similar phenomenon occurred with E. Perhaps the most ever recorded is that reported by Bijlmer in 1946. moreover. 76) 43. When the female worms were fully grown and distended with eggs.68. The behaviour of these worms was studied further by Koch who reported his observations on ten infected children i n 1925. they commenced their descent into the large intestine and finally deposited their eggs in the rectum and on the perianal skin 92. He understood that worms crawled out onto the perianal skin at night. and that they sometimes "lost their way" and could be found in the vulva (Diseases of Women. Section 1) 43. vermicularis when he wrote: "The symptoms are aggravated in the evenings and at bedtime" 4.444 A History of Human Helminthology found in the small bowel. on occasion reaching the peritoneal cavity 53. RECOGNITION OF THE CLINICAL FEATURES The cardinal feature of Enterobius infection. but Koch never observed any returning to the bowel 51. The habits of these worms became well-known and passed into folk-lore with one writer remarking: They will crawl out. When it was shown in 1916 by Stewart that Ascaris lumbricoides larvae liberated from eggs in the stomach migrated through the tissues of the hos t before returning to the bowel. perianal itching which is worst at night.000 worms in the bow el of a 40 year old emaciated man who had died in Holland 7. was recognized two and a half thousand years ago by Hippocrate s (Epidemics. Koch observed as many as 65 worms migrating in this fashion from one child.The observations of Koch were confirmed a few years later by Reardon who also showed that each female worm deposited about 11. The external migration of worms began in the early hours of sleep and lasted about three hours.44. the fecund female worms passe d into the caecum where they congregated whilst most of the male helminth s remained in the jejunum and ileum. This exacerbation of symptoms at night has led some commentators to conclude that Avicenna was referring to E. Many worms wandered into the female genitalia. No evidence of such larva l migration was found in mice and other animals infected with E.000 eggs 69. in order that they may shew their exploits to the doctor in the morning. is attested to by it s . Book 2. Book 2. vermicularis 41. It had in fact been known for yea rs that female adult worms sometimes wandered into the female genitalia. After copulation. he found at autops y approximately 10. and old women sometimes amuse themselves by seeing how many they can catch in a night. The laying of eggs began almost immediately and was completed within 15-20 minute s depending upon the amount of moisture present. vermicularis. The consensus of opinio n now is that the majority of infectio ns with this worm are asymptomatic. von Moty reported that he had found threadworms either in the appendix itself or in the intestine in three out of five cases o f appendicitis in his own practice. behavioural disturbances and scholastic difficulties . insomnia. they render the patient's life miserable. There were no significant differences in symptomatology. and which is often annoying enough. by the intolerable itching which they occasion.In females they sometimes escape into the vagina. and. DEVELOPMENT OF DIAGNOSTIC METHODS Until relatively recent times. and even. von Moty was supported enthusiastically by Blanchard and Metchnikof f (reviewed in1). some for and som e against this hypothesis. particularly if the worm burden is high. trichiura and A. Many articles appeared subsequently. improved in color. and disappearance of dark circles under the eyes afte r treatment"8. vermicularis infection caused appendicitis. 1 9% of the children were infected. in his opinion. lumbricoides may play a role in the genesis of appendicitis 64. T. restlessness. he . Still dre w attention to an apparent relationship between appendicitis and the presence of E. a clinician. 25 This account would be just as acceptable in any textbook published today..Enterobiasis similarity with the description provided by Date in 1872: 445 Threadworms may exist in considerable numbers without their presence being marked by any very striking symptoms. An unrealistic attempt was made to link Enterobius infection with trichotillomania (hair-pulling) 81. In 1899. In this view. vermicularis. either by the patient.. of adul t worms passed spontaneously. Küchenmeister has recounted one such case: a shoemaker came to me for advice as the Oxyurides disturbed him at night. but tending towards the belief that enterobiasis was so frequent that the association was merely coincidental 27. Further they believed that: "Many infested children showed gains in weight . In 1902. Debate raged for years as t o whether E. and wander about in the anal folds. with violent itching. the infection may cause enuresis. As soon as he went to bed and got warm.. threadworms do not cause much harm.. vermicularis 82. vaginitis . and cause troublesome leucorrhoea.Beyond the local irritation which they occasion. between the infected and uninfected groups 87. but they generally excite a good deal of local irritation... Weller and Sorenson published their observations of 505 children two years later. but that some infections may cause pruritus a ni. including the frequency of pruritus ani. Brady and Wright reviewed 200 cases of enterobiasis and claimed that in addition to pruritus ani. or another observer. attempted to free themselves by biting. In contrast. He believed that this frequency could hardly be accidental and suggested that E. the diagnosis of enterobiasis was dependent upon the discovery. Whether or not enterobiasis caused other clinical manifestations became a matter of controversy.29. In 1939. the Oxyurides began to march out of his anus. Once when he did not know what to do with himself.34. The cellophane was the n flattened out on a glass slide. then a cover slide placed in position and the specimen examined microscopically for eggs39 .. vermicularis infection could be diagnosed easily by scraping perianal skin with a spatula and then cleaning the spatula on the edge of a slide..446 A History of Human Helminthology wakened his wife and begged her to see whether she could not discover what it was that troubled him so much. and since then. By means of a light. provided an alternative approach and in his review in 1877. Oleinikow showed that E. the latter being used to seal the cellophane in a test tube for transport. UNDERSTANDING THE EPIDEMIOLOGY It had long been recognized that although persons of all ages may be infected with threadworms.Thousands have ascarides when they are young and never have them afterwards. In 1937. Thus. although there is an isolated report of doubtful significance by Schmidt wh o infected himself with the worm and observed his blood eosinophil level ris e from within normal limits to 28% five weeks later 77. this has become the most popular and enduring of the diagnostic techniques used in enterobiasis. particularly in families became understandabl e when the direct transmission of infection was demonstrated by Leuckart 59. United States of America 30. Graham described a modification of this swab i n which the cellophane was replaced by transparent Scotch cellulose tape 35. however. she always did him the same service. and with the recognition that eggs could be fully embryonated soon after discharge . the constitution frequently becomes so unfit for the continuance of these worms that they are absolutely shaken off without any physic at all. D r Elliotson in his "Lectures on Worms" in 1833 wrote: "There can be no doubt that children are much more disposed to ascarides [= E. The oldest record is of Enterobius ova found in coproliths. further. a couple of drops of caustic soda added. The finding of eggs in the faeces has been used recently to demonstrate the prehistoric existence of infection. and not only so. whenever he was again troubled. A few years later. particularly after B eaver indicated that the preparation could be cleared with toluene 6. lumbricoides] than others. It is generally held that Enterobius infections do not produce an eosinophilia. In 1929.000 BC. but as age advances. 28 The clustering of infection. This consisted of a glass rod wrapped in cellophane at the point and perforating a rubber cork at the other end. vermicularis] and to lumbrici [= A. and picked them off. dated approximately 8. children were infected much more frequently.. Heller put forward the possibility of diagnosin g infection by means of finding eggs in rectal mucus 42. the woman found the little white worms. this method was much more reliable than looking for eggs in faeces 67. Maurice Hall described the "NIH swab" for the diagnosis of enterobiasis.55 The discovery of Enterobius eggs. that were discovered in Utah . Proof that such eggs were viable wa s provided by Schüffner and Swellengrebel in 1949 when they infected seve n doctors and students with eggs which had lain in room dust for three days o r longer80. for they found eggs and even whole adult worms under the nails and the skin fold s around the nails93. age. particularly in persons plagued with pruritus ani. it became apparent that in these countries. and consequent rage. Subsequently. food.Enterobiasis 447 into the external environment. he had freely bitten the live worms in halves between his teeth. moist air. It was then an easy matter to transfer these eggs to th e mouth.20 Although it had been known since the time of Zenker and Heller that egg s were transmitted commonly by the fingers. The increased ease with which enterob iasis could be diagnosed following the introduction of the NIH swab resulted in a new appreciation of how common the infection was. warm atmosphere 47. vermicularis had little respect for sex. E. Cobbold has recounted what he considered to be a remarkable an d foolproof method of ensuring such reinfection: One aristocratic person. being caught under the finger nails and in the nail-folds. who was infected by myriads of these entozoa. only 1% of schoolchildren on the island of Guam in the Pacific Ocean were infected in 1947 83 whereas all of the schoolchildren surveyed in Amsterdam during World War II wer e infected79. Thus. Lentz was not satisf ied that this was the whole explanation for infections often recurred despite all appropriate precautions bein g taken. Not only was the carriage of eggs in bedding . cool air. but Zenker and Heller showed how easily auto infection could occur. His findings were confirme d several years later when investigators in the United States revealed that house dust was frequently contaminated with ova 66. while all were kille d rapidly by a dry. it was determined that most eggs survived for 48 hours when kept in cool. but that the majority were dead after this period in dry. Futhermore. He then carried out some experiments which showed conclusively that the ova could become airborne following activities such as restless movements under bedclothes and changing the bedding 58. Infection was found to be less common in tropica l countries that in nations in temperate zones. air and so on feasible. confessed to me that in his extreme distress. THE SEARCH FOR EFFECTIVE TREATMENT AND PREVENTIVE MEASURES Countless remedies have been used do wn through the ages for the management . He had thus exposed himself to a terrible revenge since multitudes of the ova entering his mouth subsequently found their way into the stomach and intestines. race o r socio-economic status23. Many surveys showed that a third or more of the population in a number of countries was infected. . garlic and wormwood.. however.. either from the patient's own person. santonin. therefore. quassia.. It was clear to him that treatment and hygiene had to go hand in hand: Obviously.19 He concluded. some cases prove obstinant and apparently incurable. lime-water. though: For my own part.. Adults will take a larger dose in an infection .. You thus send it immediately on the parts where the worms reside... requesting both immediate and permanent relief. I am in the habit of enforcing the utmost attention to cleanliness.Patients also will come to you. it is at least some satisfaction to know that the worst of cases may be overcome by perserverance in the application of appropriate remedies in combination with the employment of hygienic measures . Elliotson (1833) considered that oil of turpentine was the most effic acious agent and should be given by the anal route: In the case of ascarides (= E.an ounce of more. purity of the water used for drinking and other domestic purposes. taking care to impress upon you the impossibility of their swallowing active aperients or cathartics. local washings after defaecation... as they are more properly termed. not only as regards the person of the patient himself or herself. but I have satisfied myself that no single drug. oral medicaments were required which would bring th e parasites within reach of the clysters. that relapse was alm ost certainly the result of ingesting more eggs. In this view. in the curative treatment of ascarides. at the same time. particularly the caecum. The difficulties of treating enterobiasis were emphasized in 1874 by Cobbold in his usual verbose an d pompous style: Gentlemen.it is part and parcel of adequate treatment to recommend such prophylactic measures as should be likely to reduce the liability of reinfection within the lowest possible limits. .. vermicularis). iron sulphate and gentian. chloric ether. or from other individuals. some of them. usually in the form of an enema.I am free to admit that.28 Küchenmeister (1855) listed a number of drugs including oil. I may say that I have ransacked the Pharmacopoeia for permanently effective remedies. various preparations of steel. You cannot find any remedial agent that exerts what may be called a specially poisonous or specific action upon the threadworm. you cannot expect an amount of success equal to that which ought to be obtained in the case of tapeworms. can be employed with any certainty of success. Cobbold went on to say.. the removal and .19 He then went on to list drugs which had been recommended including assa foetida and aloes. or any combination of drugs. and it will often bring away thousands. mixed with gruel..If. He emphasized the irrationality of giving enemas alone when it was known that worms could be found throughout the length of the bowel. especially ladies..it is best to give the oil of turpentine by injection. especially bed-clothing. castor oil. or oxyurides. Frequent lavaments. From a drachm to half an ounce may be given to a child. Bremser recorded in 1819 that Sömmering had used an olive oil enema on his son with success 10.. do what we will.448 A History of Human Helminthology of threadworm infection.but also in respect of household arrangements.. frequent changes of linen. and noted the common belief that the best time for administration o f these agents was when the moon was on the wane 55. salt. you save the patient the trouble of a filthy dose and you save the stomach from great disturbance. Tetracycline is now contra-indicated because of the recognition of its propensity to stai n permanently the teeth of children. chloramin86. washing of the floors. neomycin and phthalysulphathiazole 3. "OXYURIS INCOGNITA" . following the recognition of its anthelmintic properties by Harwood and colleages in 193840.74. Koford and White rep orted the discovery of eggs of an unknown type. all of whom were cured62. A number of antibiotics including tetracycline 61 and combinations of bacitracin and succinylsulphathiazole 15. hexylresorcinol and gentian violet 24. then this was confirmed by White and Standen who demonstrated in a controlled trial that piperazine hydrate was more effective (83% cures) than gentian violet (70%) and a lactose placeb o (17%)88. the value of pyrantel was described13 as was the administration of mebendazole 11. Manson-Bahr reported that phenothiazine was ver y effective in six children and three adults with enterobiasis. In 1942.000 soldiers examined in the laboratory car Metchnikoff during the course of a hookworm survey o f troops. Mouriquand and colleagues published. butolan75. the efficacy of a derivative o f cyanide dye. Recently. Sandground showed tha t . Cho and colleagues have shown that viprynium and mebendazole remove worms at all stages or development whereas py rantel and piperazine are inactive against the larval stages of the parasite 16.Enterobiasis 449 beating of the bedroom carpets. vermitacet (extract of Tanacetum vulgare)54 . The value of the drug was then investigated by Mehrez who wrote a thesis on the subject in 1947 63. In 1965. In 1956.. however. every kind of procedure which shall operate to prevent the re-introduction of the eggs of these very common entozoa. Davis indicated that thiabendazole was effecti ve26 while shortly thereafter. salvarsan (arsenic) 38 . They had found these ova in the faeces of 429 of 140.in short. Since they presumed that the eggs were derived from an unknow n species of Oxyuris (i. tetrachlorethylene 90.e.A SPURIOUS SPECIES OF ENTEROBIUS In 1919.. In 1951.. for the first time in the more accessible literature. Giroud noted that a patient undergoing piperazine treatment fo r another condition was cured clinically and parasitologically of enterobiasis 32.19 Over the new few decades. phthalophenon)12. Several years later. These included thymol 9. presumably indicating that each of them lef t something to be desired. pyrvinium (viprynium). and spiramycin and diphetarsone 78 were shown to be effective. Enterobius). Koford and White gave them the name of Oxyuris incognita 52. In 1940. the observation that piperazine was effective in the treatment of enterobiasis 65. was reported71. aluminium subacetate76. cupronat (copper) 50 oxylax (Tubera jalapae plus dihydrooxy. This observation was soon confirmed by a number of investigators but unacceptable side-effect became apparent and led to abandonment of the drug. a wide array of drugs was put forward for th e treatment of enterobiasis. 1973 15. KANG SY. Cited in 49 5. CLAPARÈDE. Original Arabic version. TUFTS E. BARRY JM. BREMSER JG. British MedicalJournal i: 167.278 subjects. ARISTOTLE. American Journal of Medical Science 198: 367372. WYCZALEK JV. AVICENNA. WRIGHT WH. American Journal of Tropical Medicine and Hygiene 18: 50-52.. 1981 17. Heterodera radicicola . Wien. Transactions of the Association of Fellows and Licentiates of the King's and Queen's College of Physicians in Ireland 2: 392-396. 1954 4. VANPARIJS OF . E Heitz and U C Bussemaker (Editors). The symptomatology of oxyuriasis as based on physical examinations and case histories. Korean Journal of Parasitology 19: 18-26.450 A History of Human Helminthology they were merely eggs of the plant nematode. Ueber lebende Würmer im lebenden Menschen. 1971 12. 1946 8. pp 215-436. Groombridge and Sons. Carl Schaumburg und Comp. pp 966. Journal of Parasitology 32: is 359366. 1949 7.. Translated from the 1824 French version of CLF Panoucke in 48 11. "Al Canon fi Al Tib" c. DROUGHMAN V. 1. American Journal of Tropical Medicine 29: 577-587. Radiochemical and pilot clinical study in 1. COBBOLD TS. De l'oxyurose en Indochine. graece et latine. ASKUE E. In. London. Didot. Journal of the American Medical Association 217: 313-316. The treatment of pinworm (Enterobius vermicularis) infection with bacitracin and sulfasuxidine. Journal of Pediatrics 44: 380-385. cum indice nominum et rerum absolutissimo. van WIJNGAARDEN I. 1859 18. 1925 13. Opera omnia. five volumes. 1864 19. Intestinal worms and appendicitis. 1912 10. 1906 2. Ein Buch für ausübend e Aertze. BUMBALO TS. 1939 9. Pthalyl-sulfathiazole (sulfathalidine) in th e treatment of enterobiasis. Pergamon Press. Venetiis. ANONYMOUS. 1819. SCHUERMANS VL. section 64. 1812 6. 1564. pp 284. Nebst einem Anhage über PseudoHelminthen. BEAVER PC. A lecture on the treatment of threadworm. CHO SY. Exceptional cases of oxyurias in the intestinal wall. pp 480. B ulletin de la Société Médico-Chirurgicale de l'Indochine 3: 582-584. On the origin of intestinal worms particularly the Ascaris vermicularis. 1848-1874 3. XVIII. F Dübner. Mit nach der Natur gezeichneten Abbildungen auf vier Tafeln. pp 101. Libri in re medica omnes. qui hactenus ad nos pervenere etc. Studies on oxyu riasis. BUCHOLZ CH. Genève. volume 1. Mebe ndazole in enterobiasis. BRAU. R Cavier and F Hawking (Editors). Deutsche medizinisch e Wochenschrift 51: 1914-1915. CAVIER R. International encyclopaedia of pharmacology and therapeutics. Journal of Pediatrics 43. British Medical Journal ii: 1595-1596. REFERENCES 1. Parisiis. De la formation et de la fécondation des oeufs chez les vers nématodes . Oxford. V Valgrisius . BROWN HW. LAUWERS HL. Entozoa: an introduction to the study of helminthology with reference more particularly to the internal parasites of man. BRUGMANS JP. Chemotherapy of intestinal nematodes. FUGAZZOTTO DJ. Zur Behandlung des Oxuriasis mit Oxylax. 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The relationship between appendicitis. translated by WH Jones and ET Whithington. 1937 40. GALENUS CC. SWANSON L The efficacy of phenothiazine for removal E. of ascarids from swine. American Journal of Hygiene 29: 17-24. 1879 21. 1939 24. Types of anal swabs and scrapers. Nota preliminare. Diseases of the chylopoietic system. American Journal of Tropical Medicine 17: 445-453. Milano 4: 467468. Lugduni Batavorum. HOEPPLI R.000 year old human infection.. DAVIS JH. Sampson Low.) Tokyo Iji Shinshi No. Parasites and parasitic infections in early medicine and science. University of Malaya Press. HAJOS K. HIRAISHI S. 1948-1953 44. Leipzig. MOORE GJ. In. D'ANTONI JS. HARWOOD PD. COULET E St. translated by AH Buck . 1923 28. Abstracted in Japan Medical World 4: 203. pp 861-870. GIROUD. Some experiments on the growth of Oxyuris vermicularis. GORDON H. Loeb Classica l Library. Memoirs of the Medical Society of London 5: 224-285. XII. 1941 36. 1872 26. HALL MC. 1922 39. London. Journal of Parasitology 24 (Suppl. 1833 29. Cyclopaedia of the practice of medicine. H von Ziemssen (editor). Appendiceal oxyuriasis and appendic based on a study of 26. A device for the diagnosis of Enterobius infection. 1933 35. COBBOLD TS. I. Thiabendazole in pinworm in festations. Japan Medical World 4: 118-119. HASEGAWA T. Cited in 45 22. CRAM EB. SAWITZ W. Medicorum graecorum opera quae extant. Works of. Medizinische Klinik 18 : 1619-1620. Singapore. Deutsche Zeitschrift für Chirurgie 183: 222-245. pp 228. 1924 30. volume 7. 1821-1833 32. 20 volumes. itis Archives of Pathology 16: 177-194. Enterobius vermicularis: 10. Oxyuris vermicularis and local eosinophilia in the appendix wall. Intestinal worms. Science 169: 1620. 1938 41. genera and species. American Journal of Tropical Medicine 21: 159-161. HELLER A. 2367. Gazette des Hôpitaux. American Journal of Diseases of Children 109: 567-570. Heinemann. 1959 46.Enterobiasis 451 1874 20. Lugduni Batavorum. J&A Churchill. 1922 50. Phenothiazine as an anthelmintic in threadworm and roundwor m infections. JONES MF. Systema naturae per regna tria naturae. 1930 68. two volumes. Behandlung der Oxyuriasis mit Cupronat. MEHREZ R. REARDON L. locis. tenth edition. Leipzig. NOLAND MO. . (Sur le diagnostic et l'épidémiologie dans l'enterobiase. two volumes. Classic investigJ. pp 882. 1978 49. 1939 67. RUSSELL A Tropical medicine and parasitology. 1919 53. Thèse. the number of eggs produced by the pinworm . Abteilung originale 135: 156-159. LENTZ FA. In Russian with French summary. XX. Parasitenkunde und Infektionskrankheiten. pp 452. In. synonymis. Ein Lehr. 1924 55. The distribution of the ova o f Enterobius vermicularis in household dust. Volume 1. Journal of the America n Medical Association 72: 567-569. KEAN BH. contained in th e collection of the British Museum. Les nouveaux traitements de l'oxyurose. Abteilung originale 94 : 208-236. Journal of Parasitology 25: 173-177. Discussion on the validity of certain generic names at present in use in medical helminthology. pp 823. 1947 64. Paris. KHALIL M. translated by E Lankester. WHITE AW. Leipzig. pp 132. Deutsche medizinische Wochenschrift 51: 1664. A new nematode infection of man. Die menschlichen Parasiten unddie von ihnen herrührenden Krankheiten. BG Teubner. An early contribution to medical helminthology translated from the writings of the Arabian physician Ibn Sina (Avicenna) with a short biography. LEIPER RT. Oxyurenfortpflanzung in Darm ohne Reinfektion und Magenpasse. Zur Biologie des Oxyuris vermicularis. 1867-1876 60. Animal parasites belonging to the group entozoa. On animal and vegetable parasites of the human body. KRIMER M. LOUGHLIN EH. RAPPAPORT I. Zentralblatt für Bakteriologie. LEUCKART R. REARDON L. volume 2. PHILPOT F. Deutsche medizinische Wochenschrift 50: 803-804. A manual of their natural history. Die in und an dem Körper des lebenden Menschen vorkommenden Parasiten. Catalogue of the species of entozoa. 1902 65. Archiv für Schiffs. Notes on the eggs and early development of some species of Oxyuridae. "Vermitacet" gegen Oxyuris vermicularis.) "Russian Journal of Tropical Medicine" 7: 393-401. The Sydenham Society.452 A History of Human Helminthology 47. von MOTY. diagnosis and treatment. 1925 52. 1935 59. Studies on oxyuriasis. 1941 48. Ithaca. SHOOKHOFF HB. L Salvii. American Journal o f Hygiene 33: 88-102. Zentralblatt für Bakteriologie. Lancet ii: 808-809.und Lehrbuch für Naturforscherund Aertze.und Tropen-Hygiene 30: 484-491. Holmiae. Studies on oxyuriasis. Parasitenkunde und Infektionskrankheiten .und Handbuch der Diagnose und Behandlung der thierischen und pflanzischen Parasiten des Menschen. 1951 62. Cornell University Press. Studies on oxyuriasis. Journal of Helminthology 2: 239-252. L'appendicite parasitaire. 1925 51. CF Winter'sche Verlagshandlung. MOURIQUAND G. KÜCHENMEISTER F. KOCH EW. 1758 61. Th e treatment of enterobiasis with terramycine base. LINNAEUS C. 1853 57. 1929. or intestinal worms. LEACH. genera. KOLB R. KOFOID CA. Centralblatt für Bakteriologie. Abteilung originale 31: 268-272. ROMAN E. 1857 56. Abstracted n i Tropical Diseases Bulletin 27: 983. XVI. The survival of eggs of Enterobius vermicularis under known conditions of temperature and humidity.ordines. Ueber den Befund van auf dem Peritoneum des Cavum Douglasii angewachsenen Oxyuriden. W Baird (Editor). MANSON-BAHR P. 1951 66. MOTT KE. XXIII. Journal de Médecine de Lyon 32: 189-195. pp 486. 1924 69. pp 677. 1902 54. Antibiotics and Chemotherapy 1: 588-593. COISNARD J. London. secundum classes. species cum characteribus differentiis. Essai de traitement de l'oxyurose par a l pipérazine. JACOBS L. 1855. ations. WELLS HG. MULLIN WG. 1940 63. Écho Médical du Nord 6: 217-221. Parasitenkunde und Infektionskrankheiten. OLEINIKOW SV. KNOLLER G. 1926 58. Journal of Tropica l Medicine and Hygiene 25: 65-67. Ein Hand. V. Puerto Rico Journal of Public Health and Tropical Medicine 22 : 235-253. Ueber die Naturgeschichte des Oxyuris vermicularis. Cited in 42 . 88. Piperazine in the treatment of threadworms in children. 1947 STRICKER W. M. Librairie Maloine. Thérapie 15: 648-654. HELLER A. Ueber Entozoen bei Gesiteskranken. Münchener medizinische Wochenschrift 67: 722. Neue Beobachtungen übe die Eingeweidewürmer. 84. La médecine au temps des Pharaons. Münchenener medizinische Wochenschrift 69: 400-401. 1956 SCHICKHARDT E. 1937 WUNDT N. 1938 RIAD N. GORDON LS. 71. Versammlung deutscher Naturforscher und Aertze zu Dresden. Butolan. Giessae. Medizinische Klinik 20: 750. 82. New England Journal of Medicine 224: 143-146. 74. Also. Allgemeine Zeitschrift für Psychiatrie 17: 1-31. 1763 WRIGHT WH. Journalof the American Medical Association 109: 570-573. Zur Therapie der Oxyuriasis. 149-198. 1868 ZENKER F. 1860 WEINBERGER. La médecine à travers le temps et l'espace . Preliminary report on a new antioxyuritic. 79. KARPINSKI FE. De vermibus intestinorum. 73. 1924 WELLER TH. 85. pp 27. Archiv für Zoologie und r Zootomie 3: 1-32. Public Health Reports 53: 978-984. Retrofection in oxyuriasis. Münchener medizinische Wochenschrift 91: 411-414. 1924 ZENKER F. Journal of Parasitology 10: 92-94. 80. 1922 SCHMIDT WT. MACHEZ J M. 1949 SEMON HC. 1953 WOLF. British Medical Journal ii: 755-757. Report on a clinical trial. 91. SORENSEN CW. pp 20-21. 90. 75.I. BIGUET J. pp 319. and its bearing on infection. Münchener medizinische Wochenschrift 70: 495-496. 1923 SCHNEIDER J. Tageblatt der 42. Verhandlungen der physicalisch-medicinischen Societät zu Erlangen. 1861 VIX E. Therapy wit h single doses of tetrachlorethylene. 1923 SAWITZ WG. 76. Archiv für pathologische Anatomie und Physiologie und für klinische Medicin (Virchow) 21: 360-361. Münchener medizinische Wochenschrift 71: 546-548. 1956 RUDOLPHI CA. Canadian Medical Association Journal 74: 297. ein neues Mittel gegen Oxyuriasis. 72. 1944 SCHÜFFNER W. BOZICEVICH J. 1899 STOLL NR. Paris. Enterobiasis: its incidence and symptomatology in a group of 505 children. 225-302. SWELLENGREBEL NH. 83. 93. Poquil. Richtlinien de r Therapie und Prophylaxe. Treatment of oxyuriasis with pyrrovinyquinium chlorid e (Poquil). Journal of Parasitology 35: 138-146.Enterobiasis 453 70. Eine Einfache und Zuverlassige Oxyurenbehandlung. Observations on Oxyuris vermicularis in children. 77. Ueber Möglichkeit der intraintestinalen Entwicklung von Oxyuren unte r Umgeung der Magenpassage. p 140. A newly discovered mode of infection with Enterobius vermicularis. Die Bedeutung der Staubinfektion für die Oxyuriasis. Traitement de l'oxyurose par le diphétarsone speramycine et par le diphétarsone. "Oxyuris incognita" or Heterodera radicicola. 1803 SANDGROUND JH. 1955 ROYER A. 1922 STILL GF. British Medical Journal i: 898-900. 89. 92. CHENOWETH BM. American Journal of Tropical Medicine and Hygiene 5: 538-543. British Medical Journal i: 641. Physiologisch-pathologische Bemerkungen über Oxyuris vermicularis. Low incidence ofEnterobius vermicularis in natives of Guam. Enterobius vermicularis. 1920 SCHMIDT WT. 78. 81. da s Vorkommen und die Behandlung von Oxyuris vermicularis. PECK JL. 1870 (presented 20 July 1868). 86. 1960 SCHÜFFNER W. STANDEN OD. 87. 1941 WHITE RH. ins Besondere Quber die Bedeutung. Studies on oxyuriasis. Neue Beiträge zur Oxyuriasis. Trichotillomania due to threadworms. Landmarks in enterobiasis ___________________________________________________________________ BC Adult worms have been known from ancient times and various anthelmintics have been employed 1819 Bremser discovered the male adult worm 1854 Gros showed that adult worms were located primarily in the caecum 1860 Vix recovered eggs from the perianal skin 1865 Leuckart infected himself and three students with ova and recovered adult worms from their stools two weeks later 1868 Zenker observed the stages of development of larvae in the intestines at autopsy and found male adult worms in the colonic mucus 1924 Philpot showed that the larva within the eggshell developed further in the external environment and became resistant to digestive juices 1937 Hall described the "NIH swab" for diagnosis 1941 Graham modified the swab by substituting Scotch tape for cellophane 1956 Viprynium was introduced for treatment 1969 Pyrantel was introduced for treatment 1971 Mebendazole was introduced for treatment ___________________________________________________________________ .454 A History of Human Helminthology Table 17.1. de Abreu discussed certain maladies which he had observed in Angola and Brazil between 1594 and 1606. Trichocephalus trichiurus Distribution: tropics and subtropics Life cycle: The adult worms. wrote Tratado de las siete enferme dades (Treatise on the seven diseases ) which has been described as the earliest book on tropical medicine 34. which he considered was generated spontaneously 4. In this book. a Byzantine physician who lived during the reign of Andronicus II (1328-1341 AD). The first reference to the worm is found in the works of Joannes Actuarius.Chapter 18 Trichuris trichiura and TRICHURIASIS SYNOPSIS Common name: whipworm Major synonyms: Trichocephalus dispar. the ancient writers seem to have been unaware of the existence of this parasite. Eggs are excreted in the faeces and embryonate over 2 weeks or more. he appears to have believed that they were a stage in the development of the roundworm. One of these conditions appears to be trichuriasi s which he described in his section on yel low fever. 30-50 mm in length. live attached by the head to the wall of the caecum and adjacent parts of the bowel. rarely. observation of adult worms on proctoscopy. Alexei de Abreu. Actuarius mentioned that some worms resembling thi n strings were sometimes "excreted" from the intestinal wall. and matures over 1-3 months Definitive host: humans Major clinical features: dysentery. This report received little recognition and the same fate was to befall the next description of the parasite. sigmoidoscopy or colonoscopy Treatment: mebendazole DISCOVERY OF THE ADULT WORM Despite the relatively large size of Trichuris trichiura and its not infrequent occurrence. When embryonated eggs are ingested by a human. rectal prolapse in very heavily infected persons (usually children) Diagnosis: finding eggs in the faeces. Ascaris lumbricoides. each larva hatches in the small intestine. since the worms were almost invariably found in patients dying from that disease: 455 . enters the crypts in the region of the caecum. In 1623. depending upon the temperature. the Portuguese physician and adventurer. the width of sewing thread. and soon leaves the lower part of the rectum exposed. misled some later investigators into believing that there were tw o . Body and tail are transparent. and some of the other young doctors... at the other end it elongates into a thin.. lumbricoides.. and at most a thumb's breadth in length. after th e fashion of Actuarius... others were less bent. 3 Only a limited number of copies of this book was printed (perhaps less tha n 20034). vermicularis or A.. shiny and white. in fact. but he also saw the small white eggs which could be expressed together with mucus through th e genital opening.... 52 This observation of Morgagni was unknown to the Germans who rediscovered the parasite in 1761. The specimens were then taken to Roederer and Buttner to settle the argument. the latter females.I definitely found worms. a little worm or worms are bred (white like earthworms.(TRICH-)] and (OURA) meaning "hair" and "tail". all longer than those mentioned. HA Wrisberg.456 A History of Human Helminthology In those same interior parts wrinkled corrupted and ulcerated in some patients.In another corpse I found several... No further allusion was made to the existence of this worm until Morgagni in his anatomical letters (published in about 1760) recorded his discovery of the parasite in 1740: I dissected 11 cadavers consecutively. The former are males. They lay hidden inside feces at the base of the appendix. In all them the tail is bent. an epidemic o f mucoid diarrhoea (? cholera) raged in Göttingen and killed many of th e inhabitants as well as French troopers who were stationed there.. considere d them to be merely developing E.some (were) rolled together like spirals. respectively. turning from white to somewhat dark at the tail which comprised half their length.. not very thick. They pronounced the worm to be previously undescribed and gave it the name "trichuris" because of the hairlike shape of the tail.in the part of the caecum which adjoined the appendix. soft body. the size of a thumb in the length. th e name being derived from the Greek words (THRIX) [combining for m . Whil e dissecting the body of a five year old girl. one of the medical student s accidentally opened the caecum and several worms crawled out. The first three or four that I saw were white. the head hard and black) which eroding that flesh. very thin. they have a mild. 61 Not only did Roederer manage to separate the two sexes. and eroding. about 2 mm] the length of the body is seven lines and the tail 15 lines. The greatest thickness amounts to about one-third of a line [1 line = the 12th part of a Rhenish inch. and this discovery and descrip tion did not receive the acknowledgement it deserved. One of th e students. together with the corruption it keeps rotting. The marked differences in appearance between the two sexes..They were very pointed at one end and gradually became a little thickened. Many further examples were found in subsequent autopsies and Roedere r presented the findings to a meeting of the Academy of Science at Göttingen on 10 October 1761: The worm is round and cylindrical and at one end has a blunted point. believed that these were worms of a new species but the prosector. otherwise they were totally white and as thin as a hair.. DT Wagler. threadlike tail... and in six of them. these. During the winter of 1760-1761.were. but equal in length to the last two joints of the little finger. however. The untenability of this theory was shown late r when Virchow and Leuckart discovered adult T. but Goeze but did not use binary nomenclature and gave it no specific name. that T. clear. despite the fact that the eggs of the parasite were found almost as soon as the adult worms were rediscovered in 1761. try to observe the fate of eggs and recorded : "After preserving the eggs of Trichocephalus for six months in water. He was out of luck for he did not observe the ova for long enough. meaning "hair-like head". however. Several years later. Küchenmeister put forward an entirely fallacious. Roederer. T wo recent observations provided him with stimuli for his idea. First. Schrank named it Trichocephalus hominis and Hooper later named it Trichuris vulgaris 38. Rudolphi 65 reverted to the modification by Schrank of Goeze's name for the parasite and called it Trichocephalus dispar. however. but only numerous. Küchenmeister did. He sugg ested. ELUCIDATION OF THE MODE OF TRANSMISSION The manner in which the infection was transferred from one person to another remained a mystery for many years. therefore. The true anatomical arrangement was recognized b y Goeze32 who in 1782 thought it necessary to change the name to Trichocephalos. spiralis). or at the right season of the year. and gave it the specific epithet. spiralis in the intestines of experimental animals (see chapter 22). Leidy had discovered the larvae of Trichinella spiralis (which Diesing called Trichina affinis) in the muscles of swine (se e chapter 22). Linnaeus (1771 ) had called the worm Ascaris trichiura 48. Meanwhile. In 1788. but pretty regularly arrange d globules"45. trichiura eggs excreted in human faeces were ingested by pigs and the liberated larvae migrated to the muscles (as T. hypothesis to explain the life cycle.Trichuriasis 457 different species. from the same Latin word meaning "unlik e" or "unequal" 74. Second. Küchenmeister attempted to prove this hypothesis by experiments on dogs but had no success. This remained the popular name for more than a century until 1941 when the American Society of Parasitologists 59 declared that the Rules of Zoological Nomenclature concerning priority require d reversion to the generic name Trichuris of Roederer and Buttner and th e specific designation trichiura of Linnaeus. development only took place outside of the huma n . Casimir Davaine in Paris took up the same problem and reached the following conclusions: eggs were expelled unembryonated. In 1810. dispar. n o embryos appeared. In 1800. Küchenmeister himself had recently demonstrated tha t human tapeworm infection was acquired by ingesting Cysticercus cellulosae in undercooked pork (see chapter 14). In 1855. Zeder renamed the parasite Fusaria. albeit ingenious . made one major error when he mistook the head for the tail. These larvae were in turn ingested by humans in poorly cooked meat and developed into adult Trichuris in the intestines45. and the larvae within each egg may live for over one year 22. Salvatore Calandruccio. Thus. but this remained an open question for a number of years . kept them in water until 28 July 1884 and then fed them to a dog. on 24 July. but not under my name but his. trichiura in humans was lacking. Davaine thought it unlikely that an intermediate host was required and that hatching and development probably took place directly following ingestion of mature eggs23.' This preliminary note duly appeared. lumbricoides liberated from eggs in the stomach of the host migrated through the tissues befor e returning to the gut to mature (see chapter 19). trichiura eggs on 27 June 1886. he later showed that the larvae could remain alive for five years 23. thus proving that direct infection occurred in humans an d showing that the incubation period was nearly four weeks. on 27 October 1884. much to the disgust of the former who some years later wrote a bitter letter to the Journal of Tropical Medicine and Hygiene : Calandruccio discovers the cycle of evolution of the Ascaris lumbricoides and of the Trichocephalus dispar. depressiusculus on 19 February 1884. Railliet then had a similar experience. Indeed. he found whipworm eggs in his faeces for the first time. this process took four to six months or more to complete. thus expressed 'my pupil Calandruccio'. whereas I had not made my observations in his laboratory and he was ignorant of them before my communication. Leuckart undertook some experiments with related species o f Trichuris in animals. these experiments proved that related species of Trichuris developed without an intermediate host but evidence of the same phenomenon happening with T. an associate of Grassi in Italy. These results were published. Grassi never replied in the same forum to this attack. In 1886. Eventually. with minimal acknowledgement to Calandruccio. trichiura by examining microscopically his faeces repeatedly over si x months. implying that I had studied under his direction. Leuckart fed T. crenatus ova to pigs and four weeks later recovered 50-8 0 worms.458 A History of Human Helminthology body. Fülleborn . Twenty seven days later. having assured himself that he was not infected with T. by Grassi 33 in the following year. trichiura infections. 10-30 mm long. Three months later. STUDIES OF THE BEHAVIOUR OF WORMS IN THE HOST AN D PATHOLOGICAL REACTIONS TO THEM Following the discovery by Stewart that larvae of A. swallowed some embryonated T. He collected eggs of T. he obtained 150 mature worms 57. which were close to sexua l maturity47. attention turned to the question of whether a similar phenomenon occurred in T.16 For whatever reason. and shows the experiments to Grassi who praises them and says: 'I shall publish a note under your name in a German paper. In a similar experiment . He fed embryonated eggs of Trichocephalus (= Trichuris) affinis to a lamb and 16 days later found several hundred youn g trichocephali about 1 mm in length in the intestine. Sagredo found that adult worms were not always free in th e intestinal canal. and together with polymorphonuclear leucocytes. so they were forced to abandon this hypothesis62.55. Some suggested that the head of a T. that many persons who died from cholera were not infected with Trichuris whereas the worms were often found i n persons who had died from other causes. they remained coiled in the neighbourhood of the crypts of Lieberkühn. A number of years later. but that the head. By three days after ingestion. Oudendal (1924) could not accept these views. trichiura bored its way into the intestinal mucosa to form tunnels in the bowel wall. Thereafter. and concluded that the worm did not bore or tunnel its way into the mucosa. principally in the caecum. but failed t o develop. then rolled its anterior end around it s longitudinal axis.Trichuriasis 459 examined the route of migration a nd in 1923 reported the result of experiments with species of Trichuris from man. Rather. similar hatching and penetration took place. giving rise to worms s ome 200 um in length 30. became fixed. He also found that T. the epithelial cell s which gathered around the worm lost their individuality and became a syncitium. Hartz examine d histological sections of the colonic mucosa of children with massive Trichuris infections and could find no l esions which could be attributable to the infection except for mechanical compression of the mucosal cells 35. Oudendal considered that in so doing. They found. and occasionally the whole worm were buried in a sort of tunnel in the intestinal mucosa 66. the worms matured and mated. the cells of whic h were destroyed. with eggs appearing in the faeces after five weeks 36. When Hasegawa gave T. nor merely buried in the mucus. the larvae developed directly within th e gastro-intestinal tract. he fed white rats with T. In the following year. however. He studied material obtained from the bodies of Indians and Chinese infected with the helminth. they returned to th e lumen of the bowel. however. monkeys and rabbits. of guinea pigs. trichiura ova hatched in the gut. trichiura ova then found that larvae hatched within 20 hours an d penetrated the villi of the intestine. RECOGNITION OF THE CLINICAL FEATURES The coincidence of finding many examples of Trichuris infection at the same time as an epidemic of diarrhoea was occurring led Roederer and Wagler t o speculate on the possibility that these worms may have been the cause of the latter affliction. Similarly. . The interaction between the worms and the intestinal mucosa was the n investigated by a number of pathologists. formed a closed groove simulating a tunnel 54. depressiusculus to puppies. he believed that the parasite inserted its way into the lumen of a gland. sometimes the tail. Hasegawa reported the results of similar experiments. especially in the caecum. with the larvae remaining in the mucosa fo r approximately two days. but that the larvae only survived for about four days. He showed tha t when fed to normal hosts. Yet in none of these cases could be found evidence of any symptoms which could have been ascribed to Trichuris infection11. The importance of the relationship between intensity of infection and severity of disease was underlined by the investigations of Jung and Beaver that were reported in 1951. urticaria and goitre29. as he had no uninfected subjects with whom he could compare the frequency o f symptoms. apparently thought Trichuris of so little importance that he did not even mentio n it20. dizziness. prolonged and obstinate diarrhoea with mucus plus or minus blood in the stools. Nevertheless. some being embedded in the mucous membrane while others were swimming freely in the intestinal contents 41. caecum and co lon. purpura. Swartzwelder in 1939 analysed 81 patients who wer e infected with Trichuris but no other intestinal parasites. Similarly. trichiura infection with beriberi 28. by the time Abbotts Smith came in 1863 to publish his book (which was largely a translation of much of the first edition of Davaine's textbook). but none of these postulates stood up t o critical analysis. For example. acrocyanosis dystrophica. In 1895. but that heavy infection (he instanced one with 900 worms) may produce a fairly well-defined clinical picture consisting of anaemia. and that most cases showed a mild anaemia 68. however. Those authors divided their cases into . he concluded that the clinical manifestations. Thus. cramps.72. appendicitis (see chapter 17) and a predisposition to typhoid fever 14. colicky abdominal pains and debilitation 51. Musgrave and colleagues described a "diathesis" of anaemia . He concluded tha t abdominal pain. oedema and indigestion as a consequence o f heavy Trichuris infection53. This view was supported by Kahane (1907) who reported the case of a fou r year old girl with intransigent anaemia in whom innumerable whipworms were found in the appendix.460 A History of Human Helminthology In 1838. Moosbrugger. that constipation was more frequent than diarrhoea. and vomiting were the commones t symptoms.000 worms) in children may cause dysentery. Some writers went to extreme lengths in ascribing pathogenic roles to whipworms. malnutrition and rectal prolapse31. this study was uncontrolled. it gradually became apparent that massive infections (mor e than 1. diarrhoea. in his review of intestinal worms in 18 72. Date. Fernán-Nuñez (1927) considered that trichuriasis might cause dysentery. if any. Bellingham in Ireland set himself the task of determining: whether the mere presence of these animals in the intestines must of necessity be injurious or whether they may not exist in considerable numbers even in the human subjects without causing the slightest inconvenience. were "almost unknown" 2. Furthermore. Attempts were made subsequently to link T. Moosbrugger concluded that infections of light or medium intensity were asymptomatic. pernicious anaemia .44. usually right-sided. 11 He examined 29 successive individuals at autopsy and found the worms in 26 of them. after referring to the prevailing view that this parasite was of no clinical significance. anaemia. detailed three cases of Trichuris infection in whom he observed severe complications. In July 1854.69.05 mm. especially trichuriasis.Trichuriasis 461 three grades. usually with the faeces. however. tene smus and sometimes rectal prolapse with the worms being visible easily to the naked eye on the mucosa of th e prolapsed bowel 39. The finding of eggs in faeces has been used to demonstrate the prehistori c existence of infection. Perhaps the first person to record the use of this technique was Ross who in 194 2 described the sigmoidoscopic appearances in a 2 8 year old woman with chronic . trichiura by Roederer and his colleagues. while those with heavy infection (> 30. In 1853. while examining the faeces of cats and dogs for ova of nematodes. This description by Davaine has bee n hailed incorrectly as the foundation of the diagnosis of intestinal helminthiasis by microscopical examination of the stools 5. as recorded by Roederer: "sometimes they were passed by the patient" 61.500 eggs/g faeces) usually had no symptoms. a diagnosis of trichuriasis was made only occasionally in livin g patients.500-30.000 eggs/ g faeces) had dysentery. patients with light infections (< 7. Aspöck and colleagues found ova in faeces (dated between 800 and 350 BC) obtained from saltmines in Austria 6. and urticaria. those with moderate worm burdens (7. ovoid shape. H Ulrich removed a concretion about the size of cherry stone from an inguinal abscess which had resulted from an intestinal perforation . Microscopical examination of this material disclosed ova of T. DEVELOPMENT OF DIAGNOSTIC METHODS For almost a century after the re-discovery of T. the absence of a n operculum. trichiura in the midst of other material derived from faeces 71. he found eggs of Trichuris and of an unknown tapeworm in the stools of a nine year old girl 58. when Ransom in 1856 and then Davaine in 1857 reported that int estinal helminthiasis. Thus. In the summer of 1852. and that was when worms were passe d spontaneously.000 eggs/ g faeces) sometimes had vague abdominal pains. could be diagnosed by microscopical examination of faeces fo r ova. while examining the stools of dogs with cholera. He had the opportunity to confirm thi s observation in humans several years later when he found large number o f Trichuris eggs in the faeces of an individual with meningitis. abdominal pain. and length of 0. Trichuriasis can sometimes be diagnosed and an assessment made of th e damage produced by proctoscopic or sigmoidoscopic examinations. Davaine foun d Trichuris eggs in the excrement. it occurred to WH Ransom that intestinal helminthiasis i n humans might be diagnosed by a similar means. Diagnosis was put on a simple and sound basis. the small bulges at each end. usually in the right lowe r quadrant. the patient died and large numbers of adult Trichuris were found in the caecum at autopsy 21. Davaine noted that the characteristic eggs were recognized easily by thei r brown colour. A most unusual way of diagnosing Trichuris infection was recounted by Wedl in 1854. 64 THE SEARCH FOR EFFECTIVE TREATMENT When compared with A. from the anus where the mucous membrane was seen to be covered by a layer of sticky mucus. but these frequently did not live up to expectations.73. relatively little attention was paid during the nineteenth century to the treatment of Trichuris infection. A number of investigators then proved that i t was effective in trichuriasis as well 56. In the following few decades. Spruit67 supported the view that latex of higueron was active. eucalyptus. trichiura 26. attached to some of these spots moving whipworms could be seen.462 diarrhoea: A History of Human Helminthology This confirmed the diagnosis in a remarkable manner. emetine15. Unfortunately. the crude latex needed to b e prepared freshly in order to prevent fermentation. that oil of turpentine given orally was one of the best anthelmintics 27. male fern. thymol. most conspicuous about 7 in. benzine enemas9 . . With the exception of this agent an d diphetarsone 40. and the reductions in egg counts were 85% an d 17%. none of the various anthelmintics introduced after World War II was found to be effective agains t T. ficin 60. This benzimidazole compound was synthesized by Jansse n Pharmaceutica in Belgium and shown in 1971 to be active against Enterobius vermicularis (see chapter 17). and its restricte d geographical distribution inhibited wide usage. In a preliminary survey of nine cases. the two drugs produced cure rates o f 54% and 2%. In 1922. a series of 234 patients were treated with eithe r higueron latex or oil of chenopodium. betanaphthol. and several were removed with forceps. lumbricoides and E. of the bowel. Dithiazanine was introduced in the early 1960's and wa s moderately successful but two children treated with the drug died 1. one patient passed 1956 worms afte r treatment. then the effectiveness of the elixir was investigated further by Caldwell and Caldwell in 1929. after discussing various intestinal worms including T. underlying which were several haemorrhagic spots 1-2 mm. In the early part of this century. showing a little reddening and thickening of the mucosa of the lowest 9 in. in diameter. trichiura. garlic enemas41.63 and the drug was withdrawn from the market. Accordingly. Duque Lince reported his trials of various drugs including kousso. papain50 and pentavalent arsenicals 7 were recommended. respectively. respectively17. oil of chenopodium and latex of higueron as remedies for trichuriasis an d concluded that only the last had any specific effect on T. The active agent in the latex was held by Robbins to be a proteolytic enzyme. vermicularis. a number of drugs including hexylresorcinol 46. Elliotson (1833) remarked vague ly. thymol41 and "latex of Higueron" (fig-tree sap or juice prepared from Ficus glabrata)12 were employed. trichiura until mebendazole appeared on the scene. Hoekenga reported that he had tried 13 drugs or combinations of drugs and that none was ver y successful37. In 1957. it has depended largely upon general environmental sanitary measures. no clinical manifestation s occurred10. PREVENTION AN D CONTROL It was recognized early that Trichuris infection was more common in children than in adults. remain unclear. including the sizes of the eggs and the infective larvae. Interactions between human and porcine trichuriasis in nature . These included the demonstration that the time taken for development of eggs was dependent upon temperature. Tukalevski swallowed 87 infective eggs of T.Trichuriasis 463 UNDERSTANDING THE EPIDEMIOLOGY. and differences in chromosome numbers 25. vulpis have been reported. suis eggs. Little attention has been paid specifically to the prevention and control of trichuriasis. In 1940. for example . Beer reported that a 23 year old male (presumably himself) had been infected expe rimentally with 1. Similar factors determined the epidemiology of ascariasis. human infections with T. vulpis eggs compared with . The discovery by Calandruccio that infection wa s transmitted directly without the mediation of an intermediate host paved th e way for investigations of the factors controlling the epidemiology of infection. SUIS Although some authorities have failed to differentiate between Trichuris species from humans and pigs. however. VULPIS From time to time. In 1971. and it was realized that the tw o infections tended to go hand in hand. Dinnik. As helminthiasis su rveys were undertaken in various parts of the world. Dinnik and Dinnik showed that larva e developed within 11 days at 35 oC.000 T. it is accepted generally that whipworms from these two different hosts are distinct species. suis but isolated only two larvae from his stools 51 days later 70. for it had been known since the times of Davaine that eggs were able to survive for many months under moist conditions. The other major factor determining the spread an d intensity of infection was the usage of infected human excreta to fertiliz e vegetable gardens. T. demonstrated minor morphological variations. but where it has. This resulted 60 days afterwards in a light patent infection (20 eggs/gram o f faeces) which lasted for at least ten weeks. with the diagnosis being based upon t he increased size of T. it became obvious that the infection was more frequent in tropical than temperate countries. but that 180 days were required when they were kept at 15oC24. OTHER SPECIES OF TRICHURIS T. Little in 1968 recovered such eggs from human faeces then fed 22 of them to a human volunteer who fifteen weeks later developed a patent infection which produced eggs of both normal and large sizes 49. FLAMM H. in the same five year old girl. The week. FREED JE. This observation was confirmed subsequently by Correa and his colleagues 19. 1947 16. 1971 11. Grassi! (Every man his own Professor . 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Over slijmvlies-veranderingen door den Trichocephalus dispa r veroorzaakt. 1799 39. Clinical observation s on Trichocephalus trichiurus (whipworm) infection in children. 1857 46. MOTT KE. Epistolarum anatomicarum duodeviginti ad scripta pertinentiu m celeberrime viri Antonii Marie Valsalvae pars altera. Abstracted in British Medical Journal. London. VILLAREJOS VM. HOOPER R. Die in und an dem Körper des lebenden Mensche n vorkommenden Parasiten. 1908 54. Concepto actual sobre el papel patógeno del Tricocéfalo dispar (Trichuris trichiura). A strain of Trichuris trichiura having large eggs. CLEGG MT. Epistola Anatomica XIV. CF Winter'sche Verlagshandlung. Trichocephalus dispar in der Darmwand. ROEDERER JG. 1808-1810 66. Cited in 13 58. Paris. 12: 598-600. WEDL C. Un centenaire en parasitolo gie. Trichuriasis in children. del PILAR ALIAGA M. Translated in 42 62. 1957 70. A proteolytic enzyme in ficin. 1940 71. WERSHING JM. Carl Gerold & Sohn. ROSS DF. the anthelmintic principle of leche d e higueron. new series. Boletin de la Asociacion Médica de Puerto Rico 55: 469-473. TUKALEVSKI IM. Wien. and on the occurrence of a new species of taenia in th e human body. Trichuris Roederer 1761 vs. 1974 74 ZEDER JG. 1963 64. Clinical Trichocephalus trichiurus infection. roundworm. 16th annual meeting of the American Society of Parasitologists. Siegfried Lebrecht Crusius . 1800 . V Bossigelium. 1856 59. 1854. RODRIGUEZ de CURET H. Dithiazanine intoxication. SWARTZWELDER JC. Nachrichten von der Trichuriden der Societät der Wissenschaften i n Goettingen. 1942 65. translated by G Busk. American Journal of Tropical Medicine 19: 473-481. 1762 63. Göttingische Anzeigen von Gelehrten Sachen: Unter der Aufsaicht de r königliche Gesellschaft der Wissenschaften. pp 637. De morb o mucoso liber singulis. An analysis of 81 cases. Mebendazole: treatment of trichuriasis and ascariasis in Bahamian children. pp 825. quem nuper speciminis inauguralis loco ediderunt. 1939 69. On the diagnosis of. Erster Nachtrag zur Naturgeschicht e der Eingeweidewürmer von J A E Goeze mit Zusätzen und Anmerkungen herausgegeben von Zeder. A clinical survey of fifty cases and reports of three cases with heavy infection and striking clinica l symptoms. pp 243-245. Davaine et le diagnostic des helminthiases par l'examen microscopiques des selles (1857). SPRUIT CB. RANSOM WH. London. MI LKLER JF. and treatment for. 1855 72. Leipzig. Entozoorum sive vermium intestinalium historia naturalis. Treuttel e t Würtz. Medical Times and Gazette. Meditsinskaya Parasitologiya i Parasitarn e Bolezni 9: 444. RUDOLPHI CA. EINBORN NH. RAILLIET A. The treatment of trichuriasis with Leche de Higueron. part 25. REPORT OF THE COMMITTEE ON NOMENCLATURE. Lancet ii: 97-98. 1941 60. WOLFE MS. La Presse Médicale 65: 2124. Journal of Parasitology 27: 279-282. THEORIDES J. Trichocephalus Schrank 1788. WAGLER JC. SAGREDO N. Goettingae. 1945 73. ROEDERER JG. ROBBINS BH. Journal of the American Medical Association 230: 1408-1411. 1930 61. WHITTIER L.Trichuriasis 467 57. Rudiments of pathological histology. three volumes. 1761. Chronic diarrhoea due to Trichocephalus trichiurus . Journal of Biological Chemistry 87: 251-257. pp 1370. Archiv für pathologisch e Anatomie und Physiologie und für klinische Medizin (Virchow) 256: 268-274. The Sydenham Society. Grundzuge der patho logischen Histologie. 1921 68. 1925 67. American Journal of Tropical Medicine 1: 375-380. pp 320. a case report. pp 211. American Journal of Diseases of Children 70: 289-292. Landmarks in trichuriasis ___________________________________________________________________ Actuarius described worms that were probably Trichuris de Abreu described the adult worms that he had found 20 years earlier in the bowel of patients dying from yellow fever 1760 Morgagni reported his finding 20 years earlier of the adult worms in the large bowel 1761 Wagler.468 A History of Human Helminthology Table 18. trichiura ova in his stools 27 days later 1923 Fülleborn showed in experimental animals that development of larvae took place solely within the gastrointestinal tract 1973 Mebendazole was shown to be an effective treatment by a number of investigators __________________________________________________________________ c.1. Roederer and others independently rediscovered the adult worms in the large intestine of patients dying from what was probably cholera 1856 Ransom described microscopical diagnosis by finding eggs in the faeces 1886 Calandruccio swallowed embryonated eggs and found T.1330 1623 . worms also occasionally take possession of the bowel. i. piperazine. Aristotle (384-c. and were discussed by a number of Greek and Roman writers including Hippocrates (c. which are the worse. Eggs are passed in the faeces and embryonate over several months. penetrates the intestinal mucosa. Celsus (c.155 BC) 95. rarely jaundice. and to disti nguish them from "lumbricus latus" (the broad worm. live in the lumen of the upper small intestine.525-605 AD) knew that A. or more nastily from the mouth.20 AD) wrote: Again. mebendazole. At the beginning of the Christian era. confusingly . tapeworm). and these are discharged at one time from the lower bowels.Chapter 19 Ascaris lumbricoides and ASCARIASIS SYNOPSIS Common name: roundworm Distribution: widespread. especially in tropics and subtropics Life cycle: the adult worms.200 AD)42 and Alexander Trallianus (c.460-375 BC) in his Aphorisms (III. ascends the airways to the pharynx. if not terrified by. and Pliny (23-79 AD) 21. more rarely.e. 15-30 cm long. and "ascaris" of the Greeks (which.26)57. When an egg is ingested. Roman authors referred to them as "lumbricus teres". then to the lungs where it enters the alveolar spaces. the larva hatches in the small bowel. or. the large. lumbricoides normally inhabited the upper part of the small intestin e 469 .320 BC) 6. and we observe them sometimes to be flattened. and passes via the portal system to the liver. These large roundworms were mentioned in the Egyptian Papyrus Ebers (c. 23 Galen (129-c. respectively.abdominal pain. the duration depending upon the temperature. The Greeks called these roundworms µ (HELMINS STRONGYLE) meaning "worm" and "rou nd". at times to be rounded. escaped through other orifices. intestinal obstruction. and returns to the small intestine where it matures over 8-12 weeks Definitive host: humans Major clinical features: occasionally . motile creatures resembling earthworms that he pass ed in the faeces from time to time. indicated the worm now known as Enterobius vermicularis ). is swallowed. pyrantel AWARENESS OF THE ADULT WORM Ancient man must have been w ell aware of. in view of their fancied resemblance to the common earthworm. pancreatitis Diagnosis: finding eggs in the faeces Treatment: levamisole. . Although the latter commentato r illustrated both the male and female sexual organs.. spiral muscle layer under the skin.covered with an abundance of small asperities. he clearly distinguished A. or a goose quill.. In the tenth edition of his Systema Naturae in 1758..470 A History of Human Helminthology whereas tapeworms extended over a considerable length of the bowel. Tyson found a large.133 In the following year. having placed a little of it upon a microscope. Leiper in 1926 73 claimed that the correct name was Stomachida lumbricoides (Linnaeus 1758) Perebroom 1780. a copious body fluid.. an d described the appearance of the male and female reproductive organs . he wrote: They are about the bigness of a wheat straw. Edward Tyson. that investigator s began to pay much attention to the details of the anatomical structure of these parasites. on the ground that since Linnaeus had described Ascaris vermicularis first in his tenth edition of Systema Naturae in 1758. I plainly perceived 'twas nothing else but an infinite number of small eggs. bein g mentioned in the work. The first person t o subsequently use another name for A. The first person to publish such an account (1683) was the English don. vermicularis was thought to be seated chiefly in the rectum. their surface appeared smooth. a straight intestine.. called it Stomachida. He recognized that the sexes were separate. lumbricoides was Perebroom who. however. Enterobius vermicularis should have retained this designation. At both extremes they grow narrow. Stiles and Hassall had earlier argued that Bremser's removal in 1819 of Ascaris vermicularis to the genus Oxyuris of Rudolphi eliminated it and left the name open for Ascaris lumbricoides. he misinterpreted hi s observation and thought that the female Ascaris was hermaphroditic and that the male worm belonged to a different species of helminth altogether 134. or asperities on the annuli.. These eggs when fresh. 133 On dissecting the parasite. The generic name was taken from the Gree k word (ASKARIS. Perhaps fortunately. Moreover. However. Linnaeus designated this worm Ascaris lumbricoides 77. Nei Chung.The anus is a transverse slit a little below the extreme point of the tail.I did not observe those feet.. ASCARIS) meaning "worm". and genital parts which largely filled the body cavity. appeared. as did Vallisnieri in 1713. This parasit e was also the first human helminth recorded in the Chinese literature. he discovered the eggs of Ascaris: I opened the cornua uteri and found them turgid with a milky juice. It was not until the late seventeenth century. also described the anatomy of this worm104. Their mouth is composed of three lips. their colour white. in 1780. the Italian. as in the earthworm. which was probably written about 300 200 BC59. lumbricoides (which he called "lumbricus teres") from the earthworm.. tho' to the naked eye it appeared onely as a fluid body. In 1915. but as they grew dry. the International Commission on Zoological Nomenclature by Opinion 66 confirmed this view by ruling that lumbricoides was the type species of Ascaris 61. an d E. Francisco Redi. Leiper's assertions did not receive genera l . Having observed that they were about a foot in length. as I have expressed. other worm s escaped from its interior 3. however. ELUCIDATION OF THE MODE OF TRANSMISSION It was generally held for many centuries that A.. when her father trod on it. By the middle of the nineteenth century. These small worms were innumerable. More than a century after Tyson clearl y described the eggs. I cannot but think is a mistake.. however. During the sixteenth and seventeenth centuries. Church wrote: Everyone who has examined this worm attentively when newly discharged from the body must have observed an appearance like white threads. there could no longer be any doubt that transmission depended upon eggs being excreted in the faeces.For they are not viviparous but oviparous as I have shewn" 133. does not sufficiently account for the prodigious quantity. it produced three worms about one inch long which were exactly like the parent worm.. his intestines were stuffed with a great number of living worms which were in turn filled with other smalle r worms98. lumbricoides.133 Alternatively. Dominicus Panarolus claimed that from two persons: flesh-coloured worms about 16 inches long were expelled. though. It is possible. the concept tha t Ascaris was viviparous died hard.Ascariasis 471 acceptance and the name Ascaris lumbricoides retains official recognition. In any event. was convinced that all this was nonsense: "Whatever is related of this nature. Thus. This substance has in general been supposed to the intestines of the worm filled with chyle. that are sometimes observed to be bred in animal bodies. He then went on to speculat e that infection might be acquired by worms creeping into the mouth while a person lay asleep on the ground 26. being certain of his discovery of the eggs.. arose by a proces s of spontaneous generation (see chapter 2).. i.26 The "evidence" Church advanced was that when he put a roundworm passed by a child in a cup of water and spirit. 94 Tyson. as it were together about the middle of the worm..but the fact I am going to relate seems to prove beyond doubt that this white appearance is in reality the young worms nearly fit for exclusion from the parent. he may simply have meant that a vast number of eggs wer e available to contaminate the environment. These worms bore many little worms in them and the little worms looked like so many little sticks of wood. Amatus Lusitanius told of a girl who voided a large worm and. a number o f observers came around to the view that these worms were viviparous. that Tyson may have thought erroneously that the whole cycle of reproduction and growth could occur within the same host. . folded.e. they brought forth smaller versions of themselves. Similarly. they were slender and white. Felix Platter recounted the story of a boy who died and when his abdomen was opened. like other intestinal worms. being about six inches long. for he went on to say: their containing so vast a number of eggs in the cornua uteri. however. and on being born they slithered like so many tiny serpents. lumbricoides eggs. Whe n Davaine killed the animal twelve hours later. he discovered that larvae were still viable five years afte r collection32. Subsequently. lumbricoides eggs to a cow but could find no worms in the intestines four months later. Two conditions are . Davaine summarized his findings: eggs of. At tention turned. Leuckart found that the period necessary for the development of the larvae was variable and was dependent upon th e temperature. a t which time he found living larvae within the egg shells although none of them had hatched108. he found large numbers of intact eggs in the stomach and the upper small bowel. he found that these freed larvae were expelled in the faeces. only a few free larvae could be detected.A. but the embryo only hatches when it is brought into the intestine by food or drink. In October 1862. activated by the heat of the intestines.. he discovered liberated larvae and larvae that were in the process of hatching through a small pore in the shell. therefore. lumbricoides develop outside the body of man. Furthermore. He found tha t development of larvae took four to six months or even more to be completed. the question arose as to whether or not an intermediate host was involved in this process. In particular. and reported at that time that they remained alive for more than one year 31. In a subsequen t experiment upon another rat. and the other holding unembryonated ova. to discerning the way in which this occurred. He put moistened eggs into an incubator at a temperature of 15-16 oC and found that they began to develop within 24 hours. Davaine interpreted these results as indicating that: the egg shell is not dissolved by the intestinal juices because undivided eggs were found intact in the flasks but the eggs are sufficiently softened so that the embryos within. into the stomach of a dog. He placed unsegmented A. lumbricoides eggs in water on 15 November 1854 but did not examine them again until 15 October 1855. unembryonated eggs were found. In th e latter flask. 32 In October 1861.. he fed large numbers of eggs which had been kept viable for five months to a rat. These processes were reinvestigated by Davaine in 1859.. while in the former container . could pierce it and escape. Davaine also ascertained that incubation of eggs in gastric juice in vitro did not dissolve the egg shell and permit escape of the enclosed larva. Initially. development within the egg was examined. Richter in Dresden made similar observations and showed that eggs remained alive for up t o eleven months. The first person to study this aspect was Gros in Moscow in 1849. The flasks wer e recovered from the faeces two days later and the contents examined. but require d four months to reach a perfect state o f larval development 53. He therefore performed an experiment in which he introduced two small fabri c containers. Leuckart found that larvae remained motile within the egg shells for six months and showed them to the Congress of Germa n naturalists in 1857 74.472 A History of Human Helminthology and that worms developed from them. one containing embryonated A. Similarly. Davaine gave 300-400 A. he concluded that the cow was not a susceptible host to this parasite. but in the more distal parts of the small intestine. Leuckar t considered that Davaine's experiment with rats indicated that the rat was th e intermediate host. He suggested that these creatures ingested Ascaris eggs in human excrement deposited in the garden. Unterberger showed that A. and that a larval Ascaris encysted in the muscles of a mole . maculosa (= Heterakis maculosa = Ascaridia columbae) of the pigeon developed directly. and a cat with eggs of A. the egg hatches if it remains in the intestine long enough. he ingested about 10 0 embryonated eggs of A. mystax (= Toxocara mystax = T. believed that a garden myriapod. The myriapods then parasitized variou s fruits and were eaten accidentally by humans 78. lumbricoides that had been obtained the precedin g October from the large intestine o f a cadaver and that had been cultivated since that time. which was found as an encysted larva in Leuciscus alburnus. he noted that A. In support of such an hypothesis. but in one or two children. marginata (= Toxocara canis). experiments with other ascarids suggested that no intermediate host was necessary. in view of th e unusually short incubation period that he indicated. Mosler first swallowed A. In 1868. . but later gave several dozen ova to each child. mystax of the cat and dog were transmitted in a similar fashion. and Henry (1873) found that A. was the vector. cati). rabbits. however. Battista Grassi in Italy undertook an experiment in an attempt to settle the matter. megalocephala (= Parascaris equorum). Others took up similar ideas. von Linstow (1886). a number of authors after him believed that an intermediate host was probably necessary. Leuckart in 1867 failed to achieve patent infections in dogs. This report must be viewed with some circumspection.32 Although Davaine thought that transmission was direct. A few years later . a dog with those of A. thus indicating that direct infection had occurred 51. Similarly. the eggs then hatched and the larvae encysted in their organs. he failed to infect a horse directly with eggs of A. He then fed mature eggs to a number of c hildren. pigs and mice fed wit h embryonated eggs. On 21 August 1879 (22 days later ). In whichever animal supplies these conditions. Negative results with direct feeding experiments were obtained by Mosler in 1860 . as assessed by the subsequent administration of anthelmintics. Fo r example. all of these ascarids being natural parasites of these hosts. and the free larvae excreted in the rat's faeces would mature after subsequent ingestion by humans 75. he claimed to have found Ascaris eggs in his faeces. In 1879.Ascariasis 473 doubtless necessary for this hatching: the softening of the shell by intestinal juices and the activity of the embryo under the influence of heat of about 40 oC. acus. On the other hand. lumbricoides eggs himself. fever with dyspnoea occurred a few days after administration of the eggs 85. however. but a patent infection. Likewise. Finally. continued to develop when administered to a buzzard. initially in small numbers. occurred in the adult form in the pike. failed to develop. Iulus guttulatus. These findings convinced Leuckart that there must be intermediate hosts for this group o f parasites. the embryo does not linger if the animal is not of the kind where the worm can (sic) acquire its final form. No worms were ever evacuated after anthelmintic therapy. On 20 July 1879. Heller in Erlangen in present-day Wes t Germany.474 A History of Human Helminthology Calandruccio repeated this experiment. microscopical examination showed great numbers of ova in the stools of both children. but the details were unclear. that growth an d maturation took place within the small intestine. On 24 April (86 days after infection). without having had an y overt symptoms or signs of helminthiasis. Laennec. DISCOVERY OF MIGRATION OF LARVAE WITHIN THE HOST When the development of the larva within the egg had been discovered. Grassi. Two of the three children remained in hospital and systemati c examination of their faeces for nearly three months failed to reveal any Ascaris eggs. A number of observer s including. s o abandoned the search until the end of November when he found the faeces to be full of Ascaris ova. mystax in the cat. she developed a severe bronchitis accompanied by a remittent fever . Leuckart. Leuckart studied the development of A. However. had found 18 small worms between 2. uncertainty still surrounded the nature of the events occurring betwee n ingestion of the eggs and maturation of the worms. For example. Lutz in Brazil in 1887 infected a 32 year old woman with 96 embryonated eggs over a period of one month. As discussed in chapter 18 concerning a similar study with the transmission of Trichuris trichiura. Epstei n became infected accidentally during the course of his experiments 37.75 and 13 mm in length in the small intestine of a madman. The subsequent administration of santonin expelled 2 2 Ascaris from one child and 72 worms from the other. Moreover. Epstein in Germany then infected three children experimentally by feedin g them with A. Küchenmeister and Vix had seen immature worms. Heller. Grassi published the results of thi s experiment under his own name 52. without giving due acknowledgement t o Calandruccio. According to Blanchard.55. lumbricoides in 1922 (see next section). the most important studies in this regard being done by Hallez 54. He found no eggs in the faeces over the next 20 days. A few day s later. At the beginning of January. Finally. each head had the three characteristic lips but the sexes were indeterminate 56. It seemed clear.4 mm . with a seven year ol d boy who had been infected naturally previously but had then been cured. Similar experiments by a number of subsequent investigators confirmed the result obtained by Calandruccio. Leuckart found larvae 0. she passed 35 adult Ascaris 80. however. lumbricoides ova on 28 January 1891. He had more success . At the end of September 1886. Koino infected himself successfully with A. he gave 150 eggs in a pill to the lad. however. therefore. In order to examine an analogous system. attention turned eventually to studyi ng the anatomy of the newly-liberated larvae. When she was later given an anthelmintic. He swallowed a large number o f embryonated eggs but was not able to infect himself. the boy expelled 143 ascarids about 20cm in length. At autopsy of this animal.On the sixteenth day the host is free from parasites.. Nevertheless. When the worms ha d reached 2.. Thereupon... Martin found that the larvae of the ascarids of the calf.in the bronchi.. he fed large numbers of embryonated A. the lungs appeared congested and microscopica l examination revealed numerous active larvae. First. lumbricoides. but no eggs were found. pig. they have passed from the blood vessels into the air vesicles of the lung causing haemorrhage into them. Stewart gave portions of infected lung to a pig. The intermediate host might readily contaminate the food of the definitive host and the dust and earth of his surroundings.or mouse. A few larvae were also found in the liver. On the sixth day. he advanced some possible reasons to explain this negative finding and concluded: The life history of A. the last rat died.they are (then) found.5-2 mm in length. a few only escaping in the faeces. They stayed there until they wer e 1.. losing their perforating tooth an d acquiring the three lips that were prominent in adult parasites. The larvae liberated enter the bodies of their host... Histologica l examination of the lungs of these rats r evealed larvae in the alveolar spaces and in the bronchi. lumbricoides presents an alternation of hosts. they moulted. lumbricoides ova.. so one of them was killed and abundant larvae were again found in the lungs.Ascariasis 475 long in the stomach soon after ingestion. suum eggs to a pig on 13 occasions between 20 September and 6 December 1915. lumbricoides ova between 27 September and 2 December 1915. Between four and six days after infection they are found in the blood vessels of the lungs and liver .they hatch. . he fed mature A. but no larvae were found. then passed into the intestine.. Faeces passed between six and 22 hours later contained free larvae of A..It is obvious that the transfer of the parasite from the bronchi of the rat and mouse to the intestine of man and of the pig could be readily effected.8 mm in size. The other three rats seemed to have pneumonia. horse and dog only hatched when eggs reached the small intestine.. He killed the animal two weeks later but failed to fin d any ascarids. Stewart gave A. lumbricoides developed in the same manner in humans 12. Two days after its final infection... lumbricoides. The third rat was killed 12 days after the last infection.When ripe eggs reach the alimentary canal of the rat.. Stewart interpreted these findings as indicating tha t direct infection did not occur. began to exp eriment with Ascaris in pigs in 1915. an Englishman working in Hong Kong. its faeces were examined repeatedly until 17 April 1916 . No further significant advances were made until Francis Stewart. In order to determine whether larvae in the lungs of a ra t were capable of further development in another host. 115 Stewart's paper was published in the British Medical Journal of 1 July 1916 115. On 6 April 1916.. only one small Ascaris was found. Blanchar d (1890) commented that it was likely that A. so he reverted to the modes of investigation used 50 years earlier by Davaine.. as indeed Davaine had found in rats that had been given A.. When the animal was killed on 15 December. lumbricoides ova to four rats.. A second pig was given large numbers of mature A.. suum ova three times to three of the rats and twice to the fourth rat which then received a second dose of A.. . On the other hand. subsequent events were to show that he was quite wrong in ascribing transmission to an intermediate host. or even suggested. It must be said in Stewart's defence. I hope sincerely that.109 In fact. He postulated that larvae might escape from the rodents in their saliva. precedent for this idea.121 Although Stewart made a major contribution in discovering the systemi c migration of Ascaris larvae. and will constitute a valuable addition to medical zoology. Stewart was so upset that he wrote complaining that insufficient weight had been given to his experiments on pigs in which he failed to induce direct infection and he rejected as untenable the idea that Ascaris passes through the lungs of the same host as that in which it attains full maturity 116. an editorial in the British Medical Journal discussing Stewart's first paper made no reference to his theory that rats and mice were intermediat e hosts in the life cycle of A. lumbricoides and. The mode of entry of Ascaris has perplexed everyone from the beginning of parasitology. because no intermediate host could be found. in spite of the alleged result of various experiments. in spite of the war. he fed infected rat and mouse lung to four pigs and recovered small numbers (1-15) . no doubt with the experiments of Calandruccio and others in mind. In fact. this was the first of a series of fragmented. while direct infection seemed unlikely for many reasons. of course. every facility will be given to Captain Stewart to complete his invaluable work.H. suggested instead that the complete cycle of migration through the lungs and d evelopment within the one host might occur 5. the discoverer of the life cycle of malaria. upon his work on the above subject [the life history of Ascaris lumbricoides].S. Ross added: His paper is also another proof of the common observation that important discoveries must wait until the proper kind of worker comes along to tackle them. Stewart I.476 A History of Human Helminthology In the issue of the following week. confusing and contradictory reports which were spread over the next five years. a laudatory letter written by Ronald Ross. lumbricoides larvae to pigs. That rats and mice are apparently the intermediate hosts will come as a great surprise to many. he did not give up the idea of an intermediary role for rod ents for some time. and showed that larva e obtained from the lungs could survive for up to 24 hours on damp bread 117. t hat these experiments were carried out under extremely difficult conditions during wartime..M. He himself was well aware of the deficiencies for he wrote in a footnote to one paper: The author regrets that he is obliged to publish incomplete work and pleads in excuse that he has been obliged to discontinue the research. Stewart at first placed an emphasis on his observation exactly the opposite to the correct state of affairs. Nevertheless. however. There was. However. He then repeated his attempts to transfer A. 109 No doubt with his own experie nce in mind of when he was ordered to abandon his malaria research at a critical stage in favour of studies on kala azar. for Looss had demonstrated ten years earlier a similar sequence of events in ancylostomiasis (see chapter 20). not knowing when he will have an opportunity of resuming it. appeared: Will you allow me space to offer my warmest congratulations to Captain F. the most important medical work which has been done for a long time past. but none at all could be found in the other pig killed after another five days. that this ma y have been due to the age of the animals rather than indicating that an inter mediate host was required 101. He then ingested 50 large r larvae (1. larvae migrated through the lungs with the pigs suffering from Ascaris pneumonia. two months old. Stewart undertook further experiments with A. enabled him to cling to the belief: The experiments which have been conducted so far tend to prove that the larvae from the lungs of rodents can infect the pig. Stewart reported the results of infecting two four-day-old pigs wit h 22. He swallowed A. suggested. A third pig. They then passed together with effused blood into the alveola r spaces on the sixth day and the worms ascended the bronchial tree and reached the mouth by the eighth day117. He found larvae in dilated hepatic capillaries between two and five days after infection following which they escaped through th e hepatic veins to the lungs where they were filtered out in the pulmonar y capillaries. however. and when killed 31 days later.65 mm long) recovered from the trachea of a guinea pig and foun d eggs in his faeces 75 days later 141. Stewart believed that A. however. Although Stewart wrote that these experiments could hardly be considered very satisfactory. suum larvae in rats and mice.000 eggs . Ransom and Foster in the United States repeated many of Stewart's experiments. In 1917. lumbri- . in this host too. he failed to find convincin g evidence of adult worms in the gut three to four weeks later and considered (in 1918) that while the matter was not yet fully resolved: "the evidence of these six experiments is opposed to the hypothesis of direct development without an intermediate host"121. They confirmed the systemic migration of A. but at first had a negative result. the fact that two control pigs had no worms. They also attempted to infect pigs. 117 More enduring. Ransom and Fos ter announced that A.119. Meanwhile. he continued to be plagued with uncertainty. Later in that same year (1919).Ascariasis 477 of ascarids in three of them and no worms in the fourth pig. He showed that. Sadao Yoshida reported in 1918 that it was possible for infection to be acquired from larvae obtained from an intermediate host. suum infections in pigs. no worms could be found. suum eggs. and it is probable that in nature infection in man and the pig takes place by food contaminated by rats and mice. lumbricoides larvae taken from the lungs of a guinea pig. Stewart wrote with masterly understatement: "these experiments are very puzzling" 122. Large numbers of ascarids were seen in the intestines of one pig two weeks later. Even so. However.120. on very tenuous grounds.000 A. that the larvae in the mouth were swallowed subsequently and passed through the intestines to be excreted in the faeces 118. and although they failed t o achieve patent infections. In 1919. Nevertheless. lumbricoides larvae hatched when the eggs wer e ingested then either bored their way into the venules of the portal system o r ascended the bile duct. because of repeated suggestions that no intermediate host was necessary and that migration and maturation occurred within the same host . were his studies of the migration of worms in mice. was given 50. Stewart found later. lumbricoides larvae both migrate through the lungs and develop within the intestine of the same human host 68. oesophagus and stomach.40. then by the hepatic veins and inferior vena cava through the right heart to the pulmonary vasculature. then finally penetrated into the lungs from the surface. and that later. suum eggs. and thousands of young ascarids. Koino proved that A. and that larvae in the viscera reached those location s 7 through the systemic circulation 7. man or the pig" 123. or via the mesenteric lymphatics and the thoracic duct to the venous system.87. with t he maximum output occurring five to six days after infection 88. This view was refuted by a number o f investigators who showed that larvae passed via the portal vein to the liver . Thus. five on th e next day. pierced the diaphragm. Fifty days after ingestion of eggs.that is. A single larva was found in his sputum three days after infection. the definitive host became th e intermediate host as well. were seen in the small intestine. Stewart later (1920) came round to this view when he found young worms in the small intestine of three pigs fed with A. 50 immature ascarids. Yoshida (1918) claimed on the basis of his experiments that Ascaris larvae bored their way through th e intestinal wall into the peritoneal cavity. 10 mm in length. Since Kondo 69 had shown under experimenta l conditions that artificially-liberated Ascaris larvae smeared on the ski n . 6-13 cm long. were recovered from the bowel. as is the case with certain fish ascarids.478 A History of Human Helminthology coides larvae migrated systemically in g uinea pigs and rabbits as they do in rats and mice. he took a n anthelmintic and recovered 667 immature A.100. entered th e pleural space. were found in the lungs.000 A. lumbricoides larvae could not settle in the gut initially wa s because this species may have originally re quired an intermediate host. and 178 on the fifth day. These results reinforced Ra nsom and Foster in their belief that infection was direct 102. 1-2 mm long. On 28 August. lumbricoides ova. A lamb had also been fed with ova and killed 103 days later. trachea . It died ten days later and numerous larvae. uncertainty remained about the precise route by whic h larvae reached the lungs after hatching in the gut. Ohba in 1925 showed that larvae could be excreted in the urin e during the migratory stage. for he wrote in 1920: "It is extremely probable that the worm can undergo full development in one host alone . although one of the authors considered that some larvae might also reach the liver via the peritoneal cavity. In addition. While it was now clear that systemic migrati on occurred and that worms matured in the one host. He was unable to collect any sputum on the succeeding two days because he was seriously ill but larvae were then found again for the next four days. as ha d been shown with Paragonimus 142. he ing ested 2. lumbricoides.86. Fülleborn41 put all the known facts together and postulated that the reason why A. They also infected a goat twice with A. suum eggs124. Final proof that this was indeed the case was provided by Shimesu Koin o (pen name Sui) in 1922. In 1927. 000 before therapy 91. eight months after treatment. In 1918. larvae must first penetrate either the skin or gut wall. it was accepted that the infective stage whic h emerged from the egg was a second stage larva. then pass to the lungs where they would be returned by the ciliate d epithelium to the oesophagus. the Ascaris larva moulted in the small intestine. He though t that a second ecdysis took place while the worms were in the airways. reinfection seems to occur easily following eradication of a prio r infection with anthelmintics. but there have been litte data since to support or refute this view . a Japanese study showe d showed that reinfection appeared approximately two months after treatment 93. Controversy has also surrounded the nature and timing of the moulting o f Ascaris larvae. Jung 64 believed that superinfection does not occur when eggs are newly ingested during the tenure of a curren t infection.Ascariasis 479 penetrated the integument then underwent migration. however. Thust reported that the larva moulted twice while within the egg shell 131. widespread and intensive after treatment of nearly 300 children wit h hexylresorcinol. or when such larvae penetrated the skin (as shown by Kondo' s experiment). Thus. The adult worms live for between one and two years. Yoshida ha d recognized that the first moult took place while the larvae was still within the egg shell141. Similarly. then two further moults occurred o n return of the worms to the intestine 8. For many years. but also (unusually) by eating an animal which contained larvae which had passed through that animal's lungs (as shown by the experiment o f Yoshida). In 1924. Otto and Cort in 1934 showed that reinfection was rapid. it seemed that the definitive host could be infected not only by larvae which had penetrated its own intestine (the usua l case). and who did not receive treatment. the infections were eliminated spontaneously over a period of fifteen months 66. Keller in 1931 showed that in a group of patients living in an are a unsuitable for transmission. Asada reporte d that. Similar observations on Japanese prisoner s suggested that the worms survived for an average of seventeen months (range 10-24) 58. 23. and the mean number of Ascaris eggs per gram of faeces wa s 33. shortly after hatching. In 1968. Certainly. Fülleborn believed that in order for maturation to occur. 85% of the children wer e reinfected. although Maung believed that the second ecdysis might be completed during early migration 82. The worms then live free in the intestinal lumen and have a final moult three to four weeks after infection with egg production beginning eight to twelve weeks afte r infection.000 c. Recent studies in experimental animals have shown that the third moult occurs when the larva lies within the intestinal mucosa and is about 2 mm long. Whether or not resistance to reinfection occurs is controversial though th e weight of evidence suggests that i t does not. while another investigation in the Philippines indicated that 69% of childre n were reinfected after four months and 90% were infected eight and a hal f .f. and coming on three and sometimes four times in the day or night. and a blue rim is perceivable round the under eyelid.A pulse felt. The pulse is unequal and the fever has irregular exacerbations. it is full and bounding. they shut their eyes and wish to remain silent and are offended when disturbed. but the rest of the body is wasted. William Rhind. Sometimes the worms crawling up to the stomach occasion nausea. circumscribed spot in one or both cheeks..The appearance of the countenance is changed.1 According to Hoeppli. Paulus Aegineta of Alexandria (c. making its attacks with coldness of the joints. The eyes lose their brilliance. according to prevailing circumstances. the Englis h surgeon. As late as 1829. and anorexia. gnawing pain. and again change to pale. Their eyes appear bloody. Hoeppli cites the following exchange: "What is the distinguishing feature of the pulse in a case of abdominal pain caused by worms?" somebody asked.... gave a comprehensive and remarkable account of the symptoms and signs that were then believed to attend the presence of intestinal worms (both roundworms and tapeworms): The most general symptoms observable in those affected with worms are the following: .640 AD) described in detail what he considered to be the clinical manifestations o f ascariasis: Those who have roundworms experience pain of the intestines and stomach.. their cheeks red. the Chinese physicians of around the third century AD considered that ascariasis altered the character of the pulse in various ways: A pulse felt at the upper Kuan portion to be under light tension and sliding in quality indicates that ascaris becomes active. Children have mastication and projection of the tongue. Spontaneous passage of the worms was well-known an d Hippocrates wrote that this may be preceded by abdominal pain 57..480 A History of Human Helminthology months after treatment 44. RECOGNITION OF THE CLINICAL FEATURES The number of complaints that have been ascribed to Ascaris infection over the centuries is legion.. or they vomit what they have taken. But these things occur at intervals in a short time. The nose is swelled and very generally the upper lip is somewhat .But one must not expect to find all these symptoms in all cases. it indicates the sure presence of ascaris in the abdomen. sleep with palpitations and irregular startings. and some start from their sleep with a scream. on the contrary.to be floating in quality indicates that the patient has stagnant heat in his stomach and will vomit ascaris. The physician replied: "During the ordinary abdominal pain the pulse becomes feeble and thready. 59 Again. with a red." 59 Such views changed little over the centuries. or are inflated like a bladder... and in some cases hiccough.. and that when large numbers were present. small dry tickling cough.. they can scarcely swallow for nausea. Caelius Aurelianus (c.. If..When forced to take food.450 AD) believed that these worms may cause the gnashing of teeth by sleeping children. it is generally very pale or of a leaden colour.and grinding of the teeth. but certain ones.. th e abdomen became hardened 10. the pupil is enlarged. and again fall over asleep.. or their bowels are loose with corruption of the food. too. the fluid ejected is limpid like water. Rhind thought that this was fanciful and deprecated such ideas. and these are principally felt around the umbilical region. sometimes it is quite gone and at other times it is voracious with a continual gnawing sensation in the stomach. The belly too is hard. entire worms or portions of them are perceived. the host and his guests agree very well together and give one another very little mutual trouble" 70. it has the appearance of milk and water. add some caveats: It must be remarked that all the above symptoms are not always found in the same individual. a foul tongue.107 In contrast to all-encompassing views of the symptomatology of Ascaris infection. deafness. however. except the last. the sleep is troubled and accompanied by grinding of teeth. This vague concept seemed to man y . The patient is generally lazy and indolent. such as espoused by Rhind. the strong presumption is that the cause is worms.Ascariasis 481 tumified. There are often violent gripings. it may be mentioned that worms sometimes exist. there is a bleeding from the nose. without causing any inconvenience or bad symptom whatsoever. "ref lex irritation" or "sympathetic excitation" was held to account for the diverse non-gastrointestinal symptoms commonl y blamed upon intestinal helminthiasis. and that in considerable quantities. There is a general emaciation of the body. Blindness.At the same time. Even so. exclusively indicate the presence of worms. There is also nausea and a desire to vomit. 107 Rhind did. It was recognized that roundworms were u sually located in the small intestine but occasionally they were met with in the biliary system. There is also headache. The appetite is variable. a wide range of clinic al manifestations of Ascaris infection was still accepted by many practitioners. and had been known to wander through intestinal fistulae. Küchenmeister was closer to the trut h when he wrote baldly in 1855: "as a general rule. that these parasites could occasionally cause intestinal obstruction or rarely produce jaundice. Küchenmeister did recognize. however. when this takes place. The urine is turbid and after it has deposited a sediment. delirium. and even apopleptic and epileptic fits have been known to have their origin from these worms. Sometimes. saying: like all other diseases and all other evils which are incident to man. they are to be combated and warded off by the wisdom and foresight with which he is endowed for that purpose. but may be very useful in the alimentary canal by consuming excessive nutrients and stimulating bowel movements. mouth and pharynx.. throbbing in the ears. Firstly. and w as explained on the basis of two different mechanisms33. more saliva than natural in the mouth and the breath is very fetid especially early in the morning. but more generally in the alvine secretions. Secondly. nor do any of them. and there is continual itching and irritation of both these... or respiratory system. and feels like a drum. When these symptoms occur and cannot be attributed to any other cause. gastrointestinal symptoms and signs were clearly local reactions consequent upon the presence of worms in the alimentary system. 107 The observation that worms may cause no i ll-effects had even led some observers such as Avicenna. pancreatitis or layryngea l spasm. Roeder er and Abildgaard to suggest that worms may not only be harmless. sometimes in good and sometimes in irritable temper. The last and most decisive symptom observed is that in the matter vomited. The eighth day on it decreased.000 such eggs: On the sixth day..... I have repeatedly seen cases in which the expulsion of the worm has been followed by a relief of urgent symptoms so immediate and marked as to convince me that the worm itself was the cause of the mischief. ..There was severe lumbago on the third and fourth day and pains in the gastrocnemius muscles.. But when the crisis had begun.. Respiration increased and became shallow.. it becam e accepted slowly that the passage of rou ndworms during an epileptic fit or in the course of a febrile episode was the consequence of an inhospitable milie u rather than the cause of those disturbances.... On the fifth and sixth days there was severe respiratory difficulty and the face was cyanotic. This view.. Date in 1872 summed up the attitudes prevailing at the time: It has been the fashion of recent writers.. who recovered larvae from his sputum and described hi s symptoms and signs after ingestion of 2. The truth. From the seventh day on the number of respirations decreased.As to the objective symptoms.. but it gradually fell by the wayside.. even of delicate children. The discovery by Stewart in the early twentieth century of the pulmonar y migration of Ascaris larvae caused a number of observers to look back in the literature and see evidence of pulmonary ascariasis in the patients of Mosler 85 and Lutz80 who developed respiratory symptoms shortly after the experimental ingestion of A....there was fever followed by chills. it was 155 cc.. no doubt. lumbricoides ova... except in those rare cases where they have multiplied to such a degree as to cause obstruction of the bowel. it cannot be denied that worms may and often do exist in the intestinal canal..482 A History of Human Helminthology observers to be the only reasonable explanation for the coincidence betwee n expulsion of intestinal helminths and resolution of the symptoms.was lost..m.. never give rise to symptoms of any kind.. A noticeable thing was that sputum of the fifth and sixth day contained well-mixed blood..The liver.. the rales and dullness gradually decreased..2. This was confirmed in a dramatic fashion in 1922 by Koino. of themselves.the rales [moist sounds heard on auscultation of the lungs] and dullness increased day after day until breathing became difficult and weak. On the other hand.The amount of sputum increased with the increase of coughs. The number of respirations was from 56 to 58 per minute. There was 35 cc.. Certainly the gravity of the symptoms does not appear to depend upon the number of worms. headache was severe and respiration and pulse were increased. without giving rise to any special symptoms.... The face was flushed and I was thirsty..The cough increased with the rise of temperature. Appetite. of sputum on the first day.was enlarged to two finger's breadth below the costal margin ... It began to come down by crisis on the seventh day and on the ninth day was normal. There was a large amount of output for the following few days.to assert that worms.8 and remained between 38.. On the fifth day up to 7 p. For example. is a reaction from the old notion which attributed to intestinal worms all sorts of extraordinary phenomena.seems to lie between the two extremes... It may be that reflex irritation is induced only in children of very excitable temperament.. There was a heavy feeling over the chest.It came in paroxysms with intervals of two to five minutes at the height of the attacks... or in certain peculiar states either of the general nervous system or of the intestinal mucous membrane..7 and 40. 29 Debate continued until the turn of that century over the validity of the refle x irritation theory.The temperature on the second day after the onset rose up to 39. and it is probable that Küchenmeister's summation of the situation may years ago was fairly accurate. as well as other agents. larvae were found in the sputum then eggs were recovered from the faeces two t o three months later 46. Similarly. An adult patient in Peiping. USA. for Spillman 113 showed that pulmonary ascariasis was rare in areas where transmission was continuou s throughout the year.. Gelpi and Mustafa found that outbreaks of acute respirator y infection recurring each spring among young local employees of an oi l company in Saudi Arabia were due to infection with A. rare patients have vast numbers. The spleen was not palpable. lumbricoides infections. Although Löffler's syndrome was caused commonly by migrating Ascaris larvae. and 693 worms were obtained from a two year old child with intestinal . in addition to recounting the clinical features noted by Koino. . bringing the total number to 1978 ascarids 60. liver abscess . it was recognized tha t migrating hookworm and Strongyloides larvae. China presented with a perforated intestine. lumbricoides. and out through the mouth and the nose.On the twelfth day it was scarcely palpable.. appendicitis and respiratory obstruction. intestinal obstruction is th e most frequent. Swartzwelder in New Orleans .. showed that transien t pulmonary opacities were present in chest radiographs and that there was an associated eosinophilia in the peripheral blood 79. 1488 worms were removed from a patient in Malaysia110. and have migrate d through intestinal perforations and fistulae. found in an uncontrolled and selected study that abdominal discomfort was the chief symptom.Ascariasis 483 on the right mammary line. Similar effects were noted ten years later by Voge l and Minning in Germany who gave Ascaris ova to six volunteers 136. It was then realized that this presentation was mos t common in areas where transmission was seasonal. there have been few studies of the clinical manif estations of pure intestinal ascariasis. In 1967. even though 1533 worms were removed from the peritoneal cavity at operation.68 This clinical picture was re-described in 1932 by Löffler who. Nevertheless. he died subsequently and a further 445 worms were recovered at autopsy. Because populations rarely have solitary A. Ascarides have on occasion caused obstructive jaundice. Of all the various complications. however. and that intestina l obstruction occurred in 18 patients 125. pancreatitis. In a series of 202 cases who had either solitary ascariasis or light infections with Trichuris trichiura as well. Although most individuals have only one or two worms. bu t they represent a very small fraction of the total number of infected persons . fever was quite often present. and then by Brudastov and colleagues in Russia who undertook experimental self infections16. small numbers of worms in ectopi c locations can cause significant and sometimes fatal disease. could also cause the syndrome. There have been hundreds of such reports in the literature of the twentieth century alone. 990 were recovered from a nine year old European girl and 899 from an eleven year old Hottentot in Sout h Africa76. may I think. It is perhaps most remarkable that only seven years after an argument had raged in the columns of The Lancet and the London Medical Gazette. but thought that many more had gone over the side of th e ship. as it should seem that no ova of entozoa are known which can be reconcile d with them"11. believing them possibly to be involved in the causation of cholera 126. the Rev Mr Berkeley. Wedl described the histological examination of a n intestinal concretion removed from an ingu inal abscess by H Ulrich. The diagnosis of ascariasis by microscopical examination of th e faeces was first put on a sound basis in 1856 by the English physician. Such ova i n faeces were first illustrated clea rly by Swayne in 1849. He was i n charge of 557 Indian coolie emigrants on a voyage from Calcutta to Demerara. by finding Ascaris eggs in the stools. although he had no idea of their true nature. and Ransom provided clearcut illustrations of Ascaris ova. In 1854.106 DEVELOPMENT OF DIAGNOSTIC METHODS A diagnosis of Ascaris infection has been made from time to time when adult worms are expelled spontaneously. usually in the faeces. however. W H Ransom. The diagnosis i s normally made. be not unfairly attributed to the fact that this large number of roundworms had been expelled which would otherwise have caused grave interference with the digestive functions and prevented the due assimilation of food products. to recognize such an egg in the figure h e provided. Examination of her stools revealed "very numerous ova of ascari s lumbricoides. He weighed every person then administered santo nin to everyone and recovered 989 roundworms. Indeed. Ransom described the case of a 12 year old girl who presented at the Nottingham General Hospital complaining of abdominal pain and giving a history of having passed two round worms after the administration of a n aperient. Argument over the contribution of ascariasis to malnutrition has raged fo r decades 112. that Ransom was able to write so facilely that the morphological characteristics of these eggs were well-known and were easily . the characters of which are well known and easil y recognisable"103. trichiura eggs which Wedl illustrated clearly. and the College of Physicians had been disposed to produce a report on the nature of thes e so-called "cholera bodies". other bodies were present which he noted: "most nearly rese mbled those of Ascaris lumbricoides"137. He weighed his patients again two months later and found that there was a net increase of 2240 pounds in their weight and considered that: this result.484 A History of Human Helminthology obstruction in East Africa 47. in discussing the nature of thes e bodies. but perhaps the first person to pay any serious attention to thi s subject was an English ship's surgeon. In addition to T. Percy Rendall. in 1892. The eye of faith is required. went so far as to remark that: "w e still remain to discover what they are. though doubtless due to the generous dietary provided by the Colonial Governments in some part. however. The diagnosis of ascariasis turned out to be extremely easy. Concerning purgatives. These roundworms are so large that they may be seen radiologically. Vegetable matter has bee n mistaken for Ascaris ova. While most eggs are characteristic. Schinz reported that X-ray examination of a 40 year old woman after a bismuth meal revealed a "worm-like absence of shadow"111 and that roundworms were passed after anthelmintic therapy 111. These comprised two major grou ps of compounds: purgatives which expelled worms by increasing peristalsis and stimulating intestinal secretion. Reiter described one patient in whom numerous roundworms were seen in the jejunum and ileum. In the following year. Elliotson in his lecture on worms in 1833 wrote that: .000 ova were excreted in the faeces by each femal e worm every day15. dated 800-300 BC. Miura and Nishiuchi drew attention to the appearance of the not uncommon unfertilized eggs 83. for it was found that female worms produced vast numbers of eggs. eggs have been found in human coproliths. and by Coventry and Taliaferro 27. recovered from a prehistoric salt mine in Austria9. Proffit and Walton indicated tha t ascariasis may also be diagnosed during the migratory phase by finding larvae in gastric aspirates 99. For example. In 1922. Many years later. while skin reactivity in such patients was described by Brunner 18. The immunological diagnosis of ascariasis has not proved to be particularly useful. and from the intestinal contents of a girl's body (600 BC) recovered from a peat bog in East Prussia 127. variations occur and mistakes have been made in diagnosis. perhaps the most famous example being the erroneous report by Tullis that 90% of asthmatics who lived in a non-endemic area in Canada had ascariasis 67. In 1924. THE SEARCH FOR EFFECTIVE TREATMENT Over the centuries. Brown and Cort calculated that approximately 200. a large number of agents has been used for the treatment of ascariasis. Ghedini in 1907 described complement fixing antibodies in the serum of patients with Ascaris infection48. Davaine in France likewise demonstrated Ascaris eggs in the faeces of a child who ex pelled subsequently five or six adult worms30. particularly with contrast radiography.132.Ascariasis 485 recognizable. and another in whom an Ascaris was seen lying coiled in the stomach 105. In the following year. Fr itz reported that X-ray examination had revealed ascarids wandering from the duodenum into the stomach 39. animal or mineral origin. Pulmonary ascariasis may be diagnosed by finding larvae in the sputum a s was shown by Koino 68. including substances of vegetable. and vermifuges. This technique had been put to use to make retrospectiv e diagnoses of ancient Ascaris infections. In 1922. which poisoned the worms themse lves. so-called because of its vermifugal properties and its fanci ed resemblance to semen. The drug was prepared from the dried. purging him violently. especially A. Another product active agains t Ascaris was helminal.. 17 beginning in 1954 with those of Brown 14 and Brumpt and Ho-Thi-Sang . rather more expensive than thymol. It is best not to give it fast lest it should create sickness and be lost. ascaridole . and especially of its superiority to all known anthelmintics in the treatment of roundworm.Ascaris properties of the alkylated phenol.36 As the century progressed. the active principle of which was kainic acid. in the first place.. Origanum and Carum (ajowa). and concluded that wormseed oil (oil of chenopodium) was a good anthelmintic in ascariasis. were first studied b y Lamson and colleagues in 1931 71 and this drug became popular for the treatment of ascariasis in the United States. the active principle of semen-contra-vermes. hexylresorcinol.. Eucalyptus oil and sundry other anthelmintics. Meanwhile. but stool examinations in order to assess the percentage of cures and the reductions in egg excretion were apparently not performed 38.4 Because of its toxicity and non-uniformity in its therapeutic effectiveness . anthelminthicum. unexpanded flower heads of the genus Artemisia. Anderson (1864) wrote: The introduction of 'santoninum' into the British Pharmacopoeia was no more than was expected by those practitioners who have for several years been convinced of its efficiency. this drug was replaced gradually in popularity by santonin. F ayard in a thesis presented in Paris in 1949 gave an account of its efficacy in some 2.. common in the United States of America. which had long been used as a popular vermifuge in Japan. cina which is common in the Midd le East. the piperazine derivative. bu t possessing the advantage of being able to be given in capsules 135. however. Digenea simplex 35.and causing extreme vertigo. prepared from Chenopodium ambrosioides var. Thes e agents included oil of chenopodium and its active principle. Thus. a dried extract of a red alga. Following the use of piperazine in enterobiasis (see chapter 17). Thus. thymol. and thymol found in a large number of plants of the genera Thymus (thyme). Elliotson advised that oil o f turpentine was one of the best remedies available: (it) should be given by the mouth and the dose then is from half an ounce to three ounces. was shown b y ..486 A History of Human Helminthology As to getting rid of worms. 70-95% of people passed roundworms on the second and third day afte r treatment. The anti.. A good dose of calomel and jalap is an old remedy and a very excellent one. santonin fell into disuse as better drugs became available.(or) twelve grains of calomel and half a drachm of rhubarb. diethylcarbamazine.The effect it generally produces is that of making the patient sick. Vervoort in 1913 compared oil of chenopodium. 36 With respect to destruction of roundworms. The efficacy of the drug in its various forms was confirmed in many published studies .. any brisk purgative may answer the purpose..000 patients with ascariasis. Betanaphthol and carbon tetrachloride also enjoyed transient popularity with some practitioners.. Ascariasis 487 Oliver-Gonzalez and colleagues in 1949 also to be effective 89. Another new series of anthelmintics. lumbricoides. tetramisole. Davaine and others on the development of the egg. and the general acceptance at the end of World War I tha t transmission was direct. In a follow-up study using varying doses of the drug. In 1970. to be active i n ascariasis50. levamisole. thiabendazole (se e chapter 21). and despite the experimental infection o f various subhuman primates with A. Finally. was shown in the same year by G oodwin and his colleagues during the course of a pilot study of its effectiveness against hookworm. one of a new series of drugs first described in 1958. Considerable uncertainty surrounded the roles of pigs and the pig ascarid in the epidemiology of human ascariasis for some time (see Ascaris suum). In 1962. While the administration of anthelmintics is the almost universal method of treating ascariasis. cured 80% of patients with ascariasis 19. Dead ascarids were then usually passed two to three days afterwards. was discovered in 1966. It transpired eventually that although pigs may be susceptible to infection with A. then a magnesium sulphate aperient was given two hours later. pyrantel pamoate was found to be useful in the treatment of ascariasis by Amato Neto and colleagues 2. and Talyzin (1954) wrote : "The above method is so simple and safe that it has often been used fo r outpatients. Jayewardene and her colleagues found that approximately 90% of patients had at least a n 80% reduction in eggs counts in the faeces 63. Do Nascimento and colleagues indicated that a new compound . In 1966. Nine years later. such as intestinal and biliary obstruction b y roundworms. Several years later. it was shown that the laevo-isomer of tetramisole. mebendazole (see chapter 3). eliminated Ascaris infection in 80-90% of patients 34. it was shown by several groups of investigators that the related compound . the pyrante l compounds. Bephenium hydroxynaphthoate. was even more active than the racemate 130. one physical measure which enjoyed some transien t popularity in the Soviet Union must be mentioned. and large groups of people can be disinfested quickly" 129. surgery has been used for most of this century to treat certai n complications of ascariasis. lumbricoides 90. was highly active against Ascaris lumbricoides 24. humans are the most . Bui-Quoc-Hong an d co-workers reported that the benzimidazole compound. One to two litres of oxygen were given intermittently over ten minutes through a duodenal tube. UNDERSTANDING THE EPIDEMIOLOGY Comprehension of the factors controlling the distribution and prevalence o f ascariasis dawned only slowly over t he seventy years between the studies in the middle of the nineteenth century by Gros. ar e enormous. THE EVOLUTION OF PREVENTIVE AND CONTROL MEASURES Many years ago. it was apparent that transmission was dependent upon frequent contamination of the soil with faeces. the ova were found to b e relatively resistant to low temperatures. fo r these materials provided a light covering to Ascaris eggs after rains. He went on to predict that modern plumbing would eventually dissolve th e partnership25. and that moist. to provide them for millions of people of poor means. however. various chemicals an d putrefaction28. Chandler wrote that A. and the words Lane wrote fifty years ago are just as apposite today: Sewered privies cleanly kept are sure safeguards for the user. Under adverse conditions . thus permitting reactivation of infection upon the return of favourabl e environmental circumstances.138. and ingestion of infected soil by children. and ingestion of contaminated eggs in various vehicles 92. The precise nature and importance of these various determinants was found to vary from region to region. and has clung to mankind through the stone. Under certain conditions. copper and iron ages up to the present day. is a task which will not be completed within the lifetime of any of us.141.139. the use of human night soil as a fertilizer in vegetable gardens was a major factor 140. such as occurred in Germany after World War II. In some areas. and educational difficulties in providing effective waste disposal systems in most endemic areas.488 A History of Human Helminthology important host of A. and to alter the habits of these so that they religiously use and clean them. Lane (1934) indicated that the most common means o f transmission were consumption of eggs adhering to vegetables or other food. 72 . probably as a result of eating vegetables and ground-fruit on land irrigated with untreate d waste water 45. promiscuous defaecation by small children was the main source of contamination138. while in other areas. A number of investigators demonstrated that larval development within the egg occurred at a faster rate in warmer temperatures. technical. Consequently. Of possible but unproven significance were inhalation of airborne eggs an d percutaneous infection by liberated larvae 72. Furthermore. lumbricoides and the major determinant of th e epidemiology of this infection. The financial. lumbricoides has been one of Man's most faithful and constant companions from time immemorial. breakdown of sanitary measures may result in an increased incidence o f ascariasis.101. But to devise privies of demonstrable effectiveness and inoffensiveness. shad y locations facilitated such development 13. In his review of the modes of infection. favourable climatic and soil factors. dessication. the drinking of contaminated water. It was shown that maximu m transmission took place when the soil was composed of clay or fine silt. thus protecting them from dessication but leaving them near the surface where they were more likely to be ingested. they may remain dormant for years. The difficulties in such a situation are almost insuperable fo r composting and the fashioning of faecal "bricks" 62 are ineffective in destroying the parasites. such measures remain beyond the financial resources of many countries that host endemic ascariasis. Galvi n (1968) infected successfully pigs with A. differences of opinion have occurred over chromosoma l numbers and biochemical and immunological characteristics. He failed to find Ascaris larvae in the sputum or evidence of intestinal infection. bu t administration of anthelmintics has to be repeated frequently because of th e persistence of viable ova in the environment. Various investigators could not discern an y morphological differences between the two form s until Sprent (1952) described alterations in the labial denticles 114. a designation given by Dujardin in 1845. but the percentage of ova which matured and the duration of infection were reduced when compared with pigs infected with A. Koino in 1922 gave 500 A. Mass treatment has been tried on a limited scale in selected localities. suilla. reliance must be placed upon thor ough cooking of the vegetables. but no adult worms were recovered from the gut 96.9% in one area of Japan over a period 20 years84. Such measures reduced th e prevalence of ascariasis from 60% to 1. and similar results were obtained in another study in the Philip pines20. Similarly. OTHER SPECIES OF ASCARIS A. lumbricoides and A. Unfortunately. Payne and her colleagues infected five young pigs with embryonated Ascaris eggs of human origin. suum. suum 43.Ascariasis 489 The problem is compounded in communities were human nightsoil is used as a fertilizer. Confusion has reigned for many years as to the relationship between A. all anima ls suffered respiratory disturbances. and contrasted t his with the results of infection of himself with A. While many workers have confirmed and extended Sprent's observations. lumbricoides: . The sam e problem has bedevilled using physiological differences in the infectivity o f roundworms derived from humans or pigs for the opposite host as a distinguishing feature. suum ova to his brother and produced a severe respiratory disease. lumbricoides ova. others have found them to be inconsistent. On the other hand. In 1925. SUUM This parasite was so named by Goeze in 1782 49. but this is of little relevance in the case o f vegetables such as lettuces and ground-fruits such as strawberries which ar e eaten raw. Under such circumstances. and sometimes individual worms could not be differentiated reliably from on e another. but has also been referred to frequently in the older literature as A. ASADA J. In Japanese. LEVI GC. Payne and her colleagues gav e A. Venetiis. On santonine: with especial reference to its use in the round an d thread-worm. AMATUS LUSITANIUS. 218-223. If there is a strain of pig Ascaris which can parasitise in human. suum ova to two human volunteers but failed to produce patent infections 96. pp 645. Medici physici praestantissimi. swallowed unknowingly large numbers of eggs in food which had been contaminated maliciously. suum eggs. The Sydenham Society. Thus. (Experimentelle Unt ersuchung ueber die Entwicklung und Infektionswege von Ascaris lumbricoides. 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Tetramisole in th e treatment of nematode infestations in man. The epidemiology of Ascaris lumbricoides in an urban population. Rudiments of pathological histology. pp 867-872. Lancet ii: 314-315. THUST R. Geneeskundig Tijdschrift voor Nederlandsch-Indië 53: 435-445. 1942 137. Experimental infection of man with Ascaris of man and pig. nomo e de' vitelli con varie lettre spettanti all storia medica e naturale. SWARTZWELDER JC. Submikroskopische Untersuch ungen über die Morphogenese des Integuments von Ascaris lumbricoides L. G Manfrè. Clinical ascariasis. Nuovo osserva zioni ed esperienze intorno all'ovaja scoperta ne' vermi tondi dell'uomo. British Medical Journal ii : 818-819. 1932. American Journal of Diseases of Children 72: 172-180. TULLIS DC.496 A History of Human Helminthology Medical Journal i: 102. TANAMAL S. 1913 136. 1919. Part V. Ascariasis 497 Table 19. Landmarks in ascariasis ___________________________________________________________________ BC Adult worms have been known since ancient times and various anthelmintics have been employed c. then recovered 667 immature worms from his intestines after anthelmintic administration 50 days after infection 1949 Fayard reported that piperazine was a useful treatment 1958 Bephenium was shown by Goodwin and colleagues to be useful for treatment 1962 Bui Quoc Hong and co-workers showed that thiabendazole was an effective treatment 1966 Tetramisole was demonstrated by Do Nascimento and colleagues to be efficacious 1969 Thienpont and colleagues showed that levamisole was even more effective than tetramisole 1970 Amato Neto and co-workers indicated that pyrantel was active 1973 Mebendazole was shown by a number of investigators to be useful in ascariasis __________________________________________________________________ . recovered larvae from his sputum several days after infection.000 eggs. larvae were liberated in the small intestine then were passed in the faeces 1879 Grassi swallowed embryonated eggs and claimed to find evidence of a patent infection 22 days later 1886 Calandruccio gave 150 eggs to a boy and recovered 143 worms after anthelmintic administration three months later 1916 Stewart found that larvae liberated from eggs in the intestines of rats underwent systemic migration through the lungs then returned to the gut 1922 Koino infected himself with 2.1.170 AD Galen knew that adult worms normally inhabited the upper small intestine 1683 Tyson described the anatomy of the worm and clearly distinguished it from the earthworm. He discovered the eggs 1849 Gros found that eggs took several months to embryonate 1856 Ransom showed that ascariasis could be diagnosed by finding eggs in the faeces 1862 Davaine showed that eggs remained viable for up to five years 1862 Davaine discovered that when embryonated eggs were fed to rats. . pyrantel. ceylanicum . live attached by the mouth to the small intestinal mucosa. ascend the airways to the pharynx. thiabendazole. Ankylostoma duodenale. and are swallowed and pass to the small intestine where they mature over 1-2 months Definitive host: A. Necator americanus and HOOKWORM DISEASE SYNOPSIS Common name: hookworm. however. the Italian doctor.. Both of these parasites. In November 1842.this worm impressed me as having really distinct generic characteristics" 70. These penetrate the intact skin and pass via the bloodstream to the lungs where they enter the alveolar spaces. Ancylostoma ceylanicum: A. blood transfusion if necessary DISCOVERY OF THE ADULT WORM In May 1838. while dissecting the body of a peasant woman who had died of pulmonary infarction in the Maggiore Hospital in Milan.humans A. iron deficiency anaemia Diagnosis: finding eggs in faeces Treatment: bephenium. causing hookworm disease Major synonyms: 1. braziliense 3.Chapter 20 Ancylostoma duodenale. Uncinaria duodenale 2. Ancylostoma duodenale: Agchylostoma duodenale. Eggs are passed in the faeces then hatch and moult twice in the soil over two weeks or so to become infective (filariform) larvae. cats. about 1 cm long. duodenale. and the specimen he found in a third patient in the following month. encountered "a little worm in the small intestine. Angelo Dubini. pulmonary infiltrates with eosinophilia. Sclerostoma duodenale.. in the midst of much gray mucus. humans Major clinical features: dermatitis.dogs. indigestion. Anchylostomum duodenale. N.. Dochmius ankylostomum. americanus . Dubini found another example of this peculiar worm in the jejunum of an old lady who had suffered with dropsy (oedema). until he came across the parasite again four and a half years later. Dubini did not publish news of this discovery. Necator americanus: Uncinaria americana Distribution: widespread. were all 499 . mebendazole. especially in the tropics and subtropics Life cycle: The adult worms. and were unisexual. then the worm was found subsequently in many countries. transparent in the anterior. On 15 December 1842. despite its moderate size. which he felt justified the erection of a new genus in which to place this worm. round mouth furnished with four hooks folded back towards the center and situated above conical eminences which project from the interior of the pharynx. When it became common to open the intestines and examine the mucosa (particularly in patients with typhoid fever and tuberculosis). Dubini found a dozen worms in the first part of the jejunum of a woman who had died from a chest abscess. then by the latter's compatriots. being a mistransliteration of the Greek words (AGCHYLOS i. a single central penis in which are inserted two small vas deferens. the female has a blunt tail which is slightly curved. Confusion and controversy reigned over the proper name of the worm. and marked by wavy yellow brown or red stripes in the posterior three quarters. possessed a complete intestinal tract with a mouth at one end and an anus at the other. blackish stomach. A number of studies were then made of the anatomy of the worm. the most complete and extensive being those of Looss in Cairo141. that in the course of 100 autopsies. Bilharz and 92 Griesinger . spread out like a fan in the male.70 Dubini named the genus Agchylostoma. There were a number of characteristics. He described the salient features: Head not distinct from body. elastic. The parasites were so frequent.. In addition to Dubini's name of Agchylostoma duodenale. Until a short period before his own era. In addition. male helminths were present. respectively. Pruner (1846) 171. Dubini's discovery was confirmed several years later in Egypt by the German 31 physician. blunt tail in the female.. to indicate its common location in the intestine. meaning "curved" and "mouth".e. also in Egypt. he gave it the specific epithet. it was called Ancylo- .about four and one half lines [= 1 cm] in length. had not been discovered earlier. the usual procedure was to wash out the intestinal lumen with large volumes of water which would probably have carried away many worms. it had not been the general practice to open the bowel at autopsy. and the worm was so small that there would have been no chance of feeling it through the intestinal wall when squeezing the gut.500 A History of Human Helminthology female worms. and this time. Posteriorly. Dubini described the worms as being: somewhat curved in on themselves. Dubini thought that was the Greek word for "hook" and intended the name to reflect the hooked shape of the body of the parasite and its prominent mouth. In 1865. Finally. ANCHYLOS because before [CH] should be transliterated as "N" and not "G") and µ (STOMA). esophagus enlarged at the bottom like a club and distinct from the spherical. A black spherical dot marks the boundary between the transparent and colored parts. the worms were ordinarily embedded in somewhat opaque mucus which made it extremely difficult to visualize them. Wucherer found the parasite in Brazil204. for they were cylindrical in shape. duodenale.70 Dubini recognized that the worms were nematodes. however. he encountered them in more than twenty cadavers. Dubini considered the reasons why the worm.. 192 In 1903.Hookworm Disease 501 stoma duodenale by Creplin (1845) 60. By Opinion 66 in February 1915. USA. Stiles concluded that: These parasites differ from all of the members of the genus Uncinaria which I can find recorded. Considerable argument took place. meaning "to kill".e. he thought that the eggs of the American worm were slightly larger. with duodenale being the type species105. Ancylostomum duodenale by Küchenmeister (1855). Smith sent specimens to CW Stiles in Washingtom as did Drs CA Claytor in Washington. and Uncinaria duodenale by Railliet (1885). Sclerostoma duodenale by Cobbold (1864). following Railliet. the International Commission on Zoological Nomenclature in Opinion 66 declared that the official name for the parasite was Necator americanus 105. DC. but did not classify the former as a new species143. Stiles described a number of morphological differences between this parasite and classical A. Adolfo Lutz in 1888 noted some differences between the Brazilian hookworm and the European form. Dochmius ankylostomum by Molin (1860). I propose to base a new species. In 1901. In addition. and Ankylostoma duodenale by Blanchard (1885-1890). Necator 193. Dubini's name should stand. amongst other names. and renamed Strongylus quadridentatus by von Siebold (1851). and appearance of the caudal bursa of male worms. including replacement of the hook-like teeth in the mouth by semilunar plates. He elevated this subgenus to generic status in 1906194. it was clear that by the law of priority. and on that account. Ancylostoma) and placed the American hookworm in the subgenus. In 1915. the location of the vulva. recognized that the worms expelled by a patient from a plantation in southern Mexico were not the same as Dubini's A. over the relative merits of Agchylostoma. Anchylostoma. Uncinaria americana. Anchylostomum duodenale by Diesing (1849-1851). and BK Ashford in Puerto Rico. Ankylostoma and Ancylostoma. Dr AJ Smith in Galveston. upon them. however. With the acceptance of the International Rules of Zoological Nomenclature (see chapter 1). Stiles suggested splitting up the genus Uncinaria (i. This information was buried in a thesis52. The name meant "the killer" and was derived from the Latin word "neco". duodenale seen in Europe and Africa and indicated clearly the differential characteristics. however. Likewise. . Camuset appreciated that the hookworm found in South America was distinct from A. the International Commission on Zoological Nomenclature settled the matter by declaring that the valid name of the genus was Ancylostoma. duodenale (which. duodenale but thought that they might be identical with Uncinaria stenocephala of dogs189. he called Uncinaria duodenalis). and was not generally known until Leger drew attention to it in 1921125. DIFFERENTIATION OF NECATOR ANCYLOSTOMA DUODENALE AMERICANUS FROM In 1868. Texas. with which view Lane later concurred 118. Leuckart supposed that these forms. Major Clayton Lane of the Indian Medical Service examined stools of prisoners in a gaol in India and in three cases found hookworms which did not conform to the ordinary type of parasite (A. Brazil73. He found that when the eggs were placed in damp earth or mud. Dochmius trigonocephalus (now called Uncinaria stenocephala) in order to study any developments which may occur within the egg. braziliense 133. braziliense and A. duodenale in Germany at the time. Dr Gomes de Faria recorded the occurrence of a new species of hookworm. and Wucherer in 1866 wrote "Nothing is known about the way in which the eggs or embryos of Ancylostoma are introduced into the human body and under what conditions they exist outside it"204. In 1951. In view of the unavailability of A. which he named Ancylostomum braziliense. then a second moult at the end of another week coincided with a marked change in the internal organization of the worms. the segmented embryo formed a larva which hatched after three or four days. in the same year that Wucherer wrote those words. must enter some intermediate host. made some observations on the related hookworm of dogs. Shortly thereafter (1913). DUODENALE In 1910. Since de Faria had described the parasite first. Biocca reviewed the relationship between A. this parasite had been recovered from a civet cat and sent to him by Willey in Ceylon142. ceylanicum 116. In the following year. but preliminary experiments were . and they were no longer able to feed. Rudolf Leuckart. Leiper expressed an opinion that A. Looss described another hookworm which he named Agchylostoma ceylanicum. which resembled Rhabditis (a free-living worm). in the intestines of cats and dogs at Manguinhos. ceylanicum and differentiated the two species on morphological grounds32. ELUCIDATION OF THE MODE OF TRANSMISSION STUDIES OF THE DEVELOPMENT OF LARVAE IN THE EXTERNAL ENVIRONMENT Dubini made little mention of hookworm ova other than to say that the elliptical eggs could be seen in the oviduct of female worms. Closer examination revealed that they were A. however. The larvae moulted after a further three days. duodenale). Not much attention was paid to the eggs over the next twenty years. Later in the same year. and to provide a rudimentary drawing of them in situ 70.502 A History of Human Helminthology DIFFERENTIATION OF ANCYLOSTOMA CEYLANICUM FROM A. This distinction was then confirmed by Rep and his colleagues in cross-breeding experiments in 1968173. ceylanicum was identical with A. this name held general sway. Gothard's tunnel to study further the extracorporeal development of hookworms. This is seen to move freely in its capsule or cyst. They then observed moulting of the parasite: This larva will gradually increase in size. it pierced the shell..166 Perroncito considered that the capsule provided some resistance to dessication and postulated that the "cysts" might be transported by the wind as well as in water then produce infection when ingested in contaminated food or water. He therefore introduced some of these third-stage larvae in muddy water directly into the gastrointestinal tract of some dogs. The larvae increased in size and cast off their cuticles once or twice. He described the anatomy of the larva in detail. Giovanni Battista Grassi. used eggs obtained from the faeces of miners infected while building the St. He failed to recognize the first moult and misinterpreted the second moult as cyst formation or encapsulation: Whilst the pharynx is greatly modified. beginning a day or so after incubation. and found that when the larva had reached a length approximately three times that of the egg. . Unfortunately. he believed that the cyst became calcified and that the larva was liberated by the hydrochloric acid of the gastric juice: After from one to two days. which completely repeats its shape. Leuckart found that they grew for eight days then moulted. then escaped from the egg shell in the same fashion as the dog hookworm. Perroncito found that the larvae hatched from the egg shells asynchronously. transparent.90 Grassi and his colleagues found that the best medium for the development of the larvae was the faeces itself. but then died. Thus..However. Eduardo Perroncito in Turin. This finding stimulated Wucherer to make similar observations on human hookworms. duodenale of humans would have a similar development and infection must be acquired by drinking free-living larvae in dirty water134. The next significant studies were not made until 1878 when the Italians. Shortly thereafter. He placed eggs in a damp place and found that larvae developed within 24 hours. Another moult took place and he recovered mature worms three weeks after infection. the skin separates a substance chitinoid (?) glassy. Wucherer was unable to pursue these investigations any further as he had insufficient laboratory resources at his disposal.. that is.. we are unable to say what happens afterward. their compatriot. as of today.and becomes one with the capsule. They observed the repeated segmentation of the embryo within the egg shell. which in a very short time is condensed. Corrado Parona and Ernesto Parona studied the development of hookworm eggs of human origin.Hookworm Disease 503 negative. Further. then recorded the progessive changes which occurred in the internal organization of the growing worm.. and forms a capsule which encloses the living larva. This convincing experiment led Leuckart to surmise that A. it will shed its skin at least twice. and that all stages of development were hastened by increased temperatures. becoming quite long and undergoing at least two moults.. [the larva's] skin separates from the salts of chalk (particularly from the carbonate of chalk). Looss. realized that it was this process that Perroncito and others had called "encystment" and was nothing more than an ordinary shedding process except that the old coat was not cast off completely. the observations and interpretations of Schulthess.166 Perroncito's conclusions were repudiated a few years later (1886) by Schulthess in Germany who correctly interpreted the "cyst formation" as representing merely a phase in ecdysis and dismissed the calcification as being a process of degeneration 184.. These phenomena were also investigated by Leichtenstern who misguidedly tried to support Perroncito's views with regard to cyst formation. buccal cavity and oesophagus. if not intentional disregard for. regardless of whether they are or are not cited in every later work. He chose the latter course and wrote: It is my intention to contribute to the improvement of our knowledge as far as I am able.. Lutz. Like Perroncito.. Looss was able to keep such larvae alive for 10-20 days in water and confirmed that they could not withstand dessication. saying that for one such as him incarcerated in Egypt and denied the scientific aids and libraries to which those in Europe were accustomed. or not.seems to contract a little in length so that the old skin extends to a degree over head and tail. Looss watched the development and hatching of the larva. Arthur Looss in Egypt re-examined the development of larvae and confirmed...136 These larvae were non-feeding. either he worked for his own pleasure and kept all his discoveries to himself..130. Parona.. Leichtenstern and others. although he did not agree with the concept of calcification. from a savage attack by Leichtenstern who charged that Looss's paper was nothing more than a re-hash of the known facts. Looss replied vigorously.the body. he had one of two choices. A second moult then occurred. then found that at the prevailing temperature (27oC). combined with a curious ignorance of. the literature129.In the great majority of cases they do not cast off the outer chitinous skin. or he published them.138 .504 A History of Human Helminthology this always becomes more rigid and friable. To this. but he did acknowledge that all the pertinent literature was not available to him. but the old cuticle was usually retained: the body membrane is seen to consist of two layers. a moult occurred after two to three days.. This statement was made despite the numerous investigations of Perroncito. although he does not appear to have been aware of it at the time. After five days. changes in the internal morphology of the larva began to take place. and it is my conviction that the merits of prior authors will prevail in any scientific question. the outer one of which begins to detach itself more and more from the body until it finally loses connection with it completely and covers it all around with an exceptionally thin and delicate chitinous coat. Grassi. Leichtenstern denied that moulting of larvae occurred128. particularly in the mouth. as could rightfully be expected in the centres of scientific life. whether the form was perfect. Ten years later. infective forms and ripe for transfer. duodenale. Looss began the paper alluded to above by saying that very little was known about the life history of A. like Schulthess.. however. This did not save him. Looss in that instance remained obdurate. Looss was not convinced that everything had indeed been clarified about the life cycle. the same trap was to befall Looss with his insistence that the transmission of schistosomiasis was direct. Although the question of the existence or non-existence of heterogony in A.. but rather be received with careful reserve and incredulity. however. a form which is essentially distinct form the parasitic ankylostoma. On the other hand. Many years later. unlike Leichtenstern. Captain GM Giles of the Indian Medical Service in Assam made observations during the course of an investigation into the aetiology of kala azar and beri beri which caused him to claim that heterogony occurred with hookworm83. for where personal convictions play the most prominent part it is not always easy for impersonal reason brought forward by others.. Later that year. Giles was .. In 1886..I foresee that my observations. Another blind alley also bedevilled a proper understanding of the in vitro development of hookworms for over thirty years. stercoralis which was sometimes found in association with hookworms in the intestines. Looss remarked somewhat pontifically: Supreme personal confidence in his method of research. Leichtenstern first put forward the proposition that hookworms underwent heterogony. and neglect inspired by this confidence of the biological probabilities pointed out by specialists on the subject. stercoralis 145. yet..126 Nevertheless. reproducing itself through unlimited generations. the same did not apply to English investigators. In 1889-1890 and quite independently of Leichtenstern. It is fortunate in the interests of science that he was soon convinced himself that he was in the wrong. he believed that Giles had inadvertently cultured S. were the reasons which made it possible that Leichtenstern was deceived. sexually mature rhabditis form. being that of an 'outsider' will not at once be accepted by zoologists. He then claimed that in eight months he had advanced knowledge further than Leichtenstern had done over many years. This view was echoed by Kynsey112 then Sonsino suggested that Giles may have cultured freeliving nematodes. or may be S..Hookworm Disease 505 In any case. He then went on to canvass the possibilities that these freeliving worms might be identical with either freeliving nematodes which frequently occur in decaying matter. i. Leichtenstern wrote categorically: "I am in a position entirely to dispose of all such doubts and objections" 126. Leichtenstern retracted these statements when further experiments convinced him of his error127. was successfully cultivated from the egg and larva of ankylostoma. Giles's views were soon opposed by Macdonald who repeated the experiments but failed to verify the findings. Leichtenstern wrote: By observing suitable culture methods. and went on to justify this assertion by describing the percutaneous penetration of infective larvae138 (see later). Such a phenomenon had been described with Strongyloides stercoralis (see chapter 21).142 Ironically.e. duodenale was settled rapidly as far as the German literature was concerned by the recantation of Leichtenstern. to gain a hearing.a freeliving. larvae developed outside the human body into a generation of sexual animals which in their turn produced offspring. 506 A History of Human Helminthology supported by Sandwith in Egypt who claimed to have raised heterogonic hookworms. Nor had sufficient attention been paid to differentiating between first-stage larvae of Strongyloides and hookworms. and at great length. the fact that the adult filaria was not known to them. Looss in 1911 examined the pitfalls into which previous workers had fallen. and the statement by Bilharz that he sometimes found female worms in the intestinal submucosa. consumed some faeces loaded with A. his colleague. He noted that the proponents of heterogony had looked at the first and last stages of development only. who wished to remain anonymous. Why these investigators should have swallowed eggs or first-stage larvae when they knew that larvae underwent further development in vitro is unclear.e. Furthermore. he was supported by Ozzard who wrote in 1902: During the last two years I have been able to completely confirm the experiments of Giles. freeliving nematode and pleaded: "It is much to be desired that the legend of heterogony of the ankylostomes should at last definitively disappear from scientific literature" 142. again without effect. Perhaps. A few years later. duodenale rhabditiform larvae. no symptoms attributable to hookworm infection had appeared and no eggs were found in the faeces. Looss was convinced that the facts had been made to fit the theory rather than vice versa. as Looss has surmised142. that Grassi and his colleagues postulated that Filaria sanguinis hominis (i. It did. the microfilaria of Wuchereria bancrofti) might be an ancylostome larva circulating in the bloodstream. after 45 days of observation. they wished to counteract the suggestion of Sangalli that eggs developed directly into adults without passing out of the body179. stercoralis or a nonparasitic. and had failed to follow carefully the evolution of individual worms. PROOF OF THE ORAL ROUTE OF INFECTION The first persons to attempt to transmit human hookworm infection experimentally were Grassi and an unnamed colleague. The suggestion was based upon the geographical coexistence of filariasis and hookworm infection. He was in no doubt that the various workers had been dealing with S. Finally. They also fed a large quantity of faeces full of eggs to a dog.160 Ozzard reiterated these views in 1909 and wrote that it was absurd to describe the freeliving adult worms as S. The subject was raised again when Giles re-asserted his views at the annual meetings of the British Medical Association in 189984 and 190085. The idea was negated rapidly. when the adult filarial worm was found . however. Likewise. stercoralis 161. but it eliminated many of them unchanged or nearly unchanged on the following day90. Grassi swallowed a large pill laden with segmenting hookworm eggs. That this is an example of dimorphism or heterogenesis I have not the slightest doubt. It was in this paper too. This immediately brought forth a response from Leiper criticizing Ozzard's assertions 132. to this parasite. Looss did not deny that oral transmission of hookworm infection could take place. In 1897. duodenale. and on examining his faeces. most of the larvae passed directly through the gastrointestinal tract without settling. for it was the first time that the percutaneous penetration of any worm was shown. which have just been described.Hookworm Disease 507 by Bancroft (see chapter 23).and the spot became extremely red. including monkeys.. The first monkey died 37 days after infection. Confirmation of this mode of infection was provided. however. He reflected. dogs and cats.. But at the same time I felt there an intense burning. He had the best results with newly-weaned animals. but even then. Arthur Looss reported that infective hookworm larvae penetrated the intact skin. DISCOVERY OF THE PERCUTANEOUS ROUTE OF INFECTION In 1898.. This was a momentous discovery. In those cases where helminths did persist in the gut. and many worms were found attached to the small bowel mucosa which was congested and contained numerous haemorrhages. but concluded that these hosts were insusceptible to infection with hookworm recovered from humans137. Leichtenstern undertook feeding experiments with human volunteers and found ova in the faeces four to five weeks after ingestion of larvae that had undergone the morphological changes. The discovery itself was serendipitous. americanus infective larvae. this was the inevitable result. The second animal died several days later and harboured small numbers of male and female adult worms106. when Joyeux in 1912 reported that he had infected monkeys (Cercopithecus patas) by causing them to swallow N. the worms did not complete their development and failed to produce fertilized ova. What . although he had ensured that they had been kept away from his mouth. Looss had attempted to infect himself experimentally with Strongyloides stercoralis. however. therefore. He then overcame this problem by cleaning his preparations and exposed a number of species of animals. He had never had any misgivings about allowing water containing hookworms to settle on his hands. In 1886. all the animals vomited the infected worms. was surprised to find numerous Ancylostoma eggs. The matter remained inexplicable to him until he had another experience: A drop of water with a high larva content fell on my hand one day and rolled off. I paid no attention to this moist spot which dried itself after a few minutes. during in vitro cultivation 127. on how this might have occurred. duodenale. It was not until twenty years after Leuckart's demonstration of the oral transmission of Dochmius trigonocephalus of the dog that it was shown that a similar mode of infection could occur with A. At first. In older animals. Looss attempted to repeat Leichtenstern's experiment by infecting experimental animals orally with A. professor of medicine at the same hospital.. Looss found that the larvae entered the skin and that they did this via the hair follicles: Inside the hair follicles the larvae crowded toward the hair papilla.508 A History of Human Helminthology was the meaning of this? The cause could only be the Ancylostoma larva. Looss persuaded an hospital attendant .. This necessitated morphological confirmation by Looss of penetration of the skin by larvae. Looss's colleague.138 In fact.) In the ensuing discussion. his hand was so swollen the next day that he thought it best to ask for medical help.. presented Looss's observations to the annual meeting of the British Medical Association 177. supported ardently the latter in this respect. One hour before operation. When particularly numerous in the same follicle.Before the fact can be accepted as more than a curiosity. FM Sandwith. later in the year (1901).The Ancylostoma larvae previously present in such abundance had disappeared except for a few very indolent ones. GM Giles. this was unsuccessful.. with the cooperation of his colleague Maddern. a section of skin was excised and histological sections were prepared.. Thereupon. Next. The most telling argument against his hypothesis was that he could have acquired the infection naturally as he lived in an endemic area. he applied some more larvae to the skin: The reddening of the skin and the burning sensation started exactly as before. on the other hand. Immediately following removal of the leg at operation. he extended his observations by infecting a 13 year old boy who was about to have his leg amputated. and remarked that he had examined Looss's histological sections when in Cairo a short while before86.. but had no repetition of the reaction. Patrick Manson.should be carried out.. he noted a considerable increase in the number of hookworm eggs in his stools138.. Having reached the hair papilla they left the follicles to penetrate the adjacent tissue of the cutis vera. a drop of fluid containing many larvae was spread out on the skin.138 Looss then repeated the process with water alone. who was professor of surgery at Kasr-el-Aini Hospital in Cairo. he tried to infect skin removed from a cadaver and heated to 37oC.147 In view of the continued scepticism. (This caused some confusion and Sandwith later had to specifically emphasize that it was Looss's and not his own research to which he was alluding178. so much so that he determined to say nothing more on the subject till he could prove his point. First. was somewhat more cynical: I would deprecate premature interpretation of the fact as indicating a phase in the normal life-history of the parasite or as a method of infection. I then scraped off the last moisture residue from the epidermis.139 and concluded "That actual penetration of the Ancylostoma larvae into the skin does occur can now be looked upon as unassailable" 139. they completely destroyed the outer root sheath.. in their place among the scraped-off epidermal cells were found numerous empty worm skins! The larvae themselves could only have penetrated the skin. despite being opposed to Looss in the matter of heterogonic development of hookworm. This assertion by Looss that hookworm larvae penetrated the skin was met with hostile criticism from a number of quarters. further experiments. Two or three months later. and postulated that the severe inflammation in ground itch might be due to bacteria associated with passage of the hookworm larvae28. various protozoa. In 1901. therefore. In order to exclude sensitization to a chemical. a portion of the soil was sterilized by heating and the experiment repeated. Microscopical examination of the used soil and an unused aliquot of the same material failed to reveal any acari. americanus). Microscopical examination of that specimen failed to reveal any larvae and Bentley concluded: Apparently. the living larvae had entered the skin. Fluid containing larvae . duodenale was then placed on his forearm. Austregesilo reported that he had infected two students (presumably with N. On application of these four specimens to the skin. began to investigate the cause of a condition variously called "ground-itch". Caldwell recorded the accidental infection of a laboratory worker with N. so he concluded that either the hookworm. a medical officer to the Empire of India and Ceylon Tea Company in Assam. India. leeches and protozoa. The first egg was found in his faeces 71 days later. eggs appeared in the faeces 67 or more days later21. rotifers. In 1901.28 Bentley then went on to consider the rarity of ground itch among the general rural population and suggested that this reflected a different method of disposal of human excreta. the typical eruption resulted. He then scraped the skin of patients with early cases of ground itch and found empty hookworm sheaths on the surface. only the one containing living hookworm larvae caused ground itch. a fungus. His next procedure was to culture soil with or without faeces containing hookworm ova for a week. but disclosed the presence of A. "pani-ghao". or a bacterium was responsible. Charles Bentley. and their entry had been followed by lesions similar in every particular to those found associated with the condition known as water-sore. take two samples from each culture. duodenale larvae. small earthworms. moistened it. The subject's faeces were examined daily for six weeks and were found to be free of hookworm ova. In the years following these observations. Bentley took some soil from a known infective area. fungi and bacteria. no eruption resulted. In order to verify this suggestion. Looss's hypothesis soon received independent confirmation from another source. Dalgetty had suggested that the affliction might be caused by an acarus (mite)62. This illness was characterized by a vesicular dermatitis of the feet which occurred epidemically in workers during the rainy season. americanus. then kill the hookworm larvae in one sample from each culture by gentle drying. minutes leeches.Hookworm Disease 509 to volunteer for an experimental infection. patent infections were produced percutaneously with a variety of species of hookworms. A drop of culture containing infective larvae of A. and applied it to the arm for six hours. Bentley then examined soil from a non-infective area and found only earthworms. and every stool for the next month was positive142. "water-itch" and "coolie-itch". which was prevalent in the tea gardens of the Indian subcontinent and in sugar plantations in the West Indies. and that these passed through the gastrointestinal tract unchanged. The only possible explanation other than that unclean habits on the part of an infected mother may have introduced ova into the mouth. Looss used dogs and infected them with the hookworm. Looss showed that larvae entered the lymphatics in the subcutaneous tissues and passed via the draining lymph nodes to the bloodstream. Looss then turned his attention to examining the course of migrating larvae within the body. . The following day. the area was grossly inflamed. For these experiments. two other routes of infection have been suggested. that larvae penetrated the skin. During their migration through the respiratory tree. then passed through the larynx to the oesophagus. raw vegetables. First. proved the truth of his theory beyond any doubt. The next question concerned the relative importance of the oral and percutaneous routes in human hookworm infection. or else entered the veins and were carried through the right heart to the lungs. A. either by drinking contaminated water or by consumption of contaminated. found immature ancylostomes in the small intestine.510 A History of Human Helminthology was spilt upon the hand and produced immediate itching. The stools became positive 38 days after infection51. Looss noted that the larvae began to grow and became prepared for the third ecdysis. DETERMINATION OF THE ROUTE OF MIGRATION OF LARVAE Having proven to his own satisfaction. After two days. Peiper in German East Africa (1912) conducted a careful series of studies and concluded that although a small proportion of infections may be acquired orally. More recently. Finally. In 1917. it has been suggested that hookworm larvae may be transmitted in breast milk. was that prenatal. and when they died nine days later. there was no doubt that infection could be acquired percutaneously. caninum. Maplestone reported the successful experimental infection of humans with A. The larvae then migrated quickly upwards along the surface of the bronchiolar. Howard reported the discovery of ova in the stool of an infant only 14 days old102. ceylanicum 148. He then infected a group of puppies and killed them at various times after infection. Thus. bronchial and tracheal epithelium. although he did not see a worm precisely in the act of escaping from a capillary to an alveolus. the usual mode of infection was undoubtedly by way of the skin. then marked bronchitis succeeded on the third day. if not to everyone else's. with larvae being either brushed off damp grass or taken up from infected soil by the feet165. which was able to complete its development in that host. then de Langen found them in the faeces of a six day old infant122. axillary lymphadenitis was present. transplacental infection had occurred. he infected some puppies percutaneously. He found larvae both in the pulmonary capillaries and in the alveolar air spaces. and in the process of defining this remarkable pathway. In 1933. Hookworm Disease 511 although that event did not take place until the worms had reached the intestines. both Fülleborn 79 and Okada158 introduced A. Yokogawa and Oiso repeated this experiment with tracheotomized dogs some ten years later. then killed six hours after the last infection. stercoralis and Ancylostoma in dogs. Fülleborn concluded that the vast majority of larvae followed the pulmonary circuit78. The first animal died 13 days later and 36 worms were found in the small bowel. they grew less rapidly and that no trace of the provisional mouth-capsule. When the former operation was performed and a dog was then infected percutaneously. and found that the larvae penetrated the skin and passed to the lungs. larvae were found in the tracheal mucus 2-6 days later. no hookworms developed in the gut. Fritz Schaudinn of the German Imperial Board of Health infected monkeys with hookworm larvae percutaneously. He then repeated this experiment with A. duodenale in dogs. In addition. thus indicating that systemic migration must have occurred. 29 and 30 June 1904. heart. lungs and intestine181. In the following year. What is clear is that worms mature in the gut two to three months after infection. Nevertheless. worms were found in the skin. and concluded that the pulmonary route was not necessary for maturation 207. percutaneously and subcutaneously. duodenale and N. was present. Lambinet produced patent infections in dogs given A. Looss's observations were soon confirmed by other workers. and the behaviour of A. Furthermore. Consequently. caninum orally. he showed that some of the larvae given orally also followed this pathway after boring through the oesophageal or gastric mucosa151. When another dog underwent the latter operation and was then infected subcutaneously. which normally appeared prior to moulting. On the other hand. Miyagawa (1916) investigated the migratory route of A. Looss presented his findings to the International Congress of Zoology in Berne in 1904 and published his results in detail in the following year141. Friedrich Fülleborn reported an extensive series of investigations on the migration of S. A number of studies have been carried out on the persistence of . The question remains incompletely resolved. caninum larvae into isolated loops of small intestine and found mature worms in the normal bowel. A second monkey was infected on 11. Fülleborn interrupted the tracheo-oesophageal route by tracheotomy or oesophagotomy in order to see whether this route was essential for the maturation of worms in the gut. caninum larvae in dogs and confirmed the pulmonary-oesophageal route after percutaneous infection. Soon afterwards. In 1914. most of the larvae made their way into the tracheal mucosa and very few reached the gut. those that did were passed in the faeces. but a few eggs were seen in the faeces. but that in their ascent of the airways. he found that most of those given orally or subcutaneously matured but that a proportion of those given percutaneously perished in the process113. americanus in humans after oral infection is unknown. the whole jejunum and even the upper half of the ileum were completely filled with fresh. much light was shed on the matter. he saw that "Two of them (the worms) were firmly attached by their heads to the mucosa.000 eggs per day197. Dubini found hookworms in many patients. may appear to be normal or else slaty.the attachment of worms to the small intestinal mucosa by their mouth and the small haemorrhages around worms.the mucosa. or also simply hypervascular. Stoll. he reached the following conclusions about the worms: . These investigations have shown that the life span of hookworms is generally one to two years. Subsequently. red. or sucking onto the intestinal mucosa. all the organs were extremely anaemic. Thousands of ancylostomes were hanging in the mucosa of the small intestine. In the next positive cadaver that he dissected (on 1 January 1845). to which the worms sometimes adhere by their oral cavity. all the worms were located in the intestinal mucus. He sought the aetiology of this condition without success for several months. When Griesinger examined the intestines. americanus produced some 9. apparently from diarrhoea. with 50-70% of worms being lost in one year. however. As a result of his accumulated observations during many post-mortem examinations. During one of his last autopsies (17 April 1852) before his return to Germany.92 He concluded. however. A twenty year old soldier died.the variety of illnesses from which these people died does not permit us to establish a relationship between the affliction and the presence of these worms70 Although he did not realize their significance. either in a free state.149. . greatly specked with black or red. therefore: . partly coagulated blood. CORRELATION OF INFECTION WITH PATHOLOGY In the first four patients found by Dubini. he found that: the duodenum. the heart was dilated and the lungs were markedly oedematous. in a small series of patients.500 ova per female worm per day99. and the mucosa was specked with small red dots"70. Many patients in Griesinger's clinic suffered from severe anaemia. while Hill in a much larger series. calculated that each female N. the syndrome being labelled by Griesinger and his colleagues as Egyptian chlorosis. . each with its own small petechia resembling the bite of a leech. Dubini made two observations necessary for a proper understanding of the pathogenesis of hookworm disease .their exclusive habitat is the duodenum and the beginnings of the jejunum.512 A History of Human Helminthology hookworms under conditions in which reinfection is not possible. although a few parasites seem to persist for many years55. The person who was able to herald the pathological importance of hookworm infection was Wilhelm Griesinger while working in Cairo. concluded that the figure was closer to 2. At autopsy. and (2) how many worms were necessary to cause illness? In 1878. Furthermore. Since then I have become convinced that the 'Egyptian chlorosis' is an entozoal disease. his colleague. but rather a cooperating agent in its production (cited in206). In his turn. Despite these tantalizing suggestions. Sangalli179 in Italy. little further attention was paid to the subject until Otto Wucherer in Brazil recognized the same phenomenon. Wucherer protested against this view205. In December 1865. Wucherer found many hookworms and the same features that Griesinger had described.206. Rather. Theodor Bilharz. like Dubini. he believed that the continuous extraction of blood for their own sustenance by hundreds or thousands of hookworms over the years would be sufficient to account for the development of anaemia. particularly those of Griesinger and Bilharz. he was called to see a slave in a sugar mill who was grossly oedematous and markedly anaemic. Subsequently. Thus was born a controversy which was to persist for decades. who carried on this work. above all an ancylostomiasis. The publication of Wucherer's findings led J R de Moura in Rio de Janeiro to examine the bodies of patients with tropical chlorosis and he also found hookworms in 91 them153 . He asserted that such haemorrhage need not be visible macroscopically. In fact. . he was convinced of a causal relationship between the two events204.92 Griesinger postulated that the daily loss of blood in the gastrointestinal tract must result in anaemia. since not only did bleeding come from the upper small bowel. The patient died within 24 hours and at autopsy. but that the symptoms and signs of disease did not by any means appear to be as serious as might have been inferred from previous descriptions.Hookworm Disease 513 It was clear that in every respect the deceased belonged to the 'chlorotics'. and had bled to death. since he found subsequently the parasites in the bodies of five more patients who had this syndrome (which he called hypoaemia or tropical chlorosis). cast doubt on the idea that hookworms caused any significant disease when he showed that autopsy examinations in the University of Pavia revealed that half of the cadavers were infected with hookworm. Wucherer made post-mortem examinations on twelve persons with other diseases and failed to find any hookworms. Griesinger left Egypt shortly thereafter and was unable to prove his views statistically. came to the same conclusions and published his observations 31 two years before Griesinger's paper appeared. but the faeces of Egyptians were copious and mushy as they consumed large quantities of bread. Camuset in French Guiana (1868) 52. There were two great questions: (1) did hookworm infection cause disease at all?. Grenet in the French colony of Comoros (1867) . In order to ensure that the association was not coincidental. The findings of Wucherer and de Moura were discussed at the Academy in Rio de Janeiro and the general opinion was reached that hookworms were not a primary and necessary cause of tropical anaemia. but had no doubt that subsequent investigators would confirm his hypothesis92. and Kérangel in the French colony of Cayenne (1868) 108 confirmed Wucherer's observations. was also the cause [when they were present].. In February 1880. He found hookworms in 76% of these individuals. Attygale in Ceylon in 1888. anaemia]. Some investigators.e. but not constantly. particularly bad air. Gothard tunnel. most of them healthy coolies en route to work from various parts of India on the Assam tea plantations. however. At the beginning of 1880. and showed that they responded to treatment with anthelmintics 57.. and that the presence of anchylostoma in these cases was of no more import in its causation that that of the lumbrici found in common with it in a large number of cases?17 Sonsino (1890) forthrightly denied any connection between hookworm infection and severe illness of the type described by Griesinger when he wrote: I think the so-called African cachexia and Griesinger's Egyptian chlorosis cannot rightly be identified with ankylostomiasis. JF McConnell reported for the first time that hookworms were present in India. Gothard anaemia was due to ancylostomiasis or to poor hygienic conditions. professor of pathology at the University. and noted that anaemia was present in only 40% of these patients. Similarly.190 In like manner. could not find ancylostomes in half of his patients with anaemia. by the outbreak of hookworm disease which occurred during the building of the St.48. ankylostomiasis enters as an element.. Considerable argument at both medical and political levels then ensued as to whether the St. it sometimes happened that a person with very few worms was in very bad health whereas some . with numbers varying from very few to hundreds. such as Bozzolo and Pagliani. and their relation to any special disease a coincidence" 144. but wrote: "My opinion is that their presence is to be regarded in the majority of cases as purely accidental. The former view eventually prevailed. Dobson in India (1893) examined the stools of 1. however. disclosed some 1500 ancylostomes in the small bowel. particularly as a result of the work of Eduardo Perroncito who found large numbers of hookworm eggs in the faeces of many patients. he realized that hookworms could not reproduce in the bowel and presumed that the worm burden depended upon the number of eggs ingested. supported the latter view. Despite their evacuation from the tunnel.514 A History of Human Helminthology The potential importance of hookworm infection was brought home to many European doctors. mainly from Piedmont. Furthermore. A post-mortem examination by Francisco-Vittoria Colomiatti. Moreover. poor light and unsuitable food. inasmuch as they are the combined result of different morbid conditions into which frequently.167. returned home ill.164. a railway tunnel in the Swiss Alps which was opened in 188347. He made no reference to the worm burden.168 The confusion over the role of hookworms in the genesis of disease is further illustrated by the following sample of views expressed over the next few years. so asked the question: Might it not also be considered with greater reason that whatever induced the disease [i. In 1882. the condition of many patients worsened and several died. one of these persons died in hospital in Turin from what had been labelled "pernicious anaemia". at least initially41.249 persons. a large number of workmen.in cases in which the anchylostoma was absent. the genesis of anaemia. may prove to be the last straw which breaks the camel's back. and is further reduced by actual famine. In August 1899. The second series of observations emanated from the Western Hemisphere. the disease then called beriberi in Assam and Ceylon was of the wet variety in both cases and may well have been related to ancylostomiasis in the form of marked hookworm-induced anaemia and consequent congestive cardiac failure. by malaria. Nevertheless.7 Two events in particular which occurred around the turn of the century did much to convince the sceptics that hookworm infection sometimes culminated in serious disease. This epidemic confirmed the pathogenicity of the parasite. Bailey K Ashford of the United States Army was put in charge of a temporary hospital to deal with the thousands of sick. in 15 cases of kala azar (which some persons had postulated was caused by hookworm infection). and other conditions tending to diminish the amount of aliment absorbed. and means of prevention. insanitary conditions underground8. and it stimulated many investigations into the habits of the larvae. and kala azar is the name now given to the disease caused by infection with Leishmania donovani. with a liberal physiological margin to draw on. homeless.159. there were only 0-36 hookworms. for "beriberi" was a rather elastic term including a number of entities such as wet beriberi (cardiac failure) and dry beriberi (peripheral neuropathy) that are now recognized as being due to thiamine deficiency. a few hundreds of minute nematodes in the alimentary canal may be a circumstance of little importance. but when the native has been half starved all his life. On the other hand. damp.Hookworm Disease 515 persons in whom there was a great abundance of parasites were robust and healthy. Kynsey in Ceylon (1887) 112 and Giles in Assam (1890) 83 were both convinced that the so-called "beriberi" of Ceylon and Assam or "kala azar" of Assam were due to ancylostomiasis. starving peasants who were mountain dwellers of Spanish descent. The first of these was the spread of ancylostomiasis from the St. where the parasites flourished in the warm. overwork. When they were fed on the nourishing diet of the . for many people developed severe anaemia.77. Belgium and England. Hungary and Germany. This occasioned some confusion. and to the coalmines of France. enteritis.in these conditions a daily steady drain of blood by a swarm of anchylostomata. dyspepsia. An anonymous commentator in the British Medical Journal came very close to the truth when he remarked in 1893: In the healthy and robust native. a hurricane wreaked havoc in Puerto Rico. though it may after all be but a small one. Miners and expatriates returning from the tropics carried hookworms with them to the congenial surroundings of the brickfields of Austria. while at the same time they tend to increase waste and destruction . whether it be the "beri-beri of Assam" or anything else69. Gothard's tunnel and elsewhere to the rest of Europe. so Dobson concluded that hookworms had no great influence as a factor in the genesis of disease. Such views were echoed by Williams203 and by Zinn and Jacoby208. the final factor which determines the starting of the vicious pathological circle. Furthermore. There are few things more remarkable in the whole history of tropical medicine than the failure to realize and the reluctance to admit. were in the past and are today in no small measure due to ankylostomiasis. Boycott (1911) said in his Milroy lectures: Taking the world as a whole. He published his findings in the following year . Thus. When they left camp and returned to their normal. with the possible exception of the malarial organisms. but that their general ineptitude. or race. even when the worm burden was small. the diarrhoea resolved but the anaemia with which they were also afflicted did not. i. on the part of many medical men. I am convinced. responsible for more unhappiness and inefficiency than any other parasite. the injurious tendency of an invasion of the body by the parasite which gives rise to ankylostomiasis. of far greater mortality than the vast majority of medical men have any conception of. This was brought about by observations flowing from the campaign to control hookworm in the southern USA just before World War I. his earlier belief that hookworm infection was a major cause of disease was confirmed fully16.. some authors began to claim that hookworms always caused disease. Several years later. It seemed that hookworm carriers. A search for malarial parasites as a cause of the anaemia revealed the presence of a blood eosinophilia which in turn stimulated inspection of the faeces for hookworm eggs. both directly and indirectly. and in places where the conditions for its propogation are favourable it may reduce four-fifths of the population to a continual state of chronic ill-health which is only terminated by the premature decease. These were found in abundance and on 24 November 1899. I suppose.The view that infection with less than 100 or 50 worms is clinically .. Ashford in Ponce sent a telegram to the chief surgeon in San Juan: "Have this day proven the cause of many pernicious.37 Around this time. carelessness..e.516 A History of Human Helminthology American soldier. Stiles in 1914 was induced to write: There still exist a number of persons who believe that light infections are of no clinical importance.25 Similarly. Ashford headed a commission for the study and treatment of anaemia. they developed diarrhoea. commonly with some secondary infection. ankylostoma is. Far from saying that hookworms were never pathogenic. progressive anemias of this island to be due to Ankylostoma duodenale. those with hookworm infection but with no apparent ill-effects from the infection. 15 Ashford"14. The large number of deaths ascribed to unknown causes. the pendulum began to swing even further away from the point at which it had at one time stood. and the great loss of life occurring among paupers found dying the streets of tropical towns. however. the tide of opinion began to turn. with Baker (1903) writing: I firmly believe that ankylostomiasis is productive. improved in health and energy after treatment. the heavy mortality attributed to general dropsy and debility. was in fact due to hookworm infection. This was interpreted as an indication that they were not simply carriers. As a result of these and other observations. and for the most part indirectly for no inconsiderable number of deaths. Practically all tropical countries are permeated with the worm. bulky diet. which had been put down to laziness. . prolific and persuasive writers on this subject. and recommended that the effects of hookworm infection on a particular population should be assessed by correlating pathogenic effects with intensity of infection before embarking upon mass treatment89. Gordon in 1925 reported that his studies of West African males revealed no effect by hookworm infection on haemoglobin level. They found that no adverse effects upon clinical status or haemoglobin level were seen when less than 100 worms were present. who were pleased with the effects of anthelmintic treatment on the health of their labourers. defining any individual who harboured parasites in his intestines but without having any symptoms or signs of the infection as a "worm-carrier" and as the subject of hookworm infection. whereas those infected persons who had dyspepsia or anaemia as a consequence of that infection were deemed to suffer from ancylostomiasis37. demonstrated that the officials of the Commission began with the premise that light infections were of little moment to the host. He quoted passages from the Reports of the Rockefeller Sanitary Commission which. where there was widespread but moderate hookworm infection. India. expounding the view either that light infections were important. than has a control group of children who did not show hookworm infection and a control group of children who did have the infection but were not treated. yet finished thoroughly convinced that even very mild infections constituted a grave handicap. they discerned no effects of this . This stimulated Lane to write: "We seem then to have no option but to conclude that light infections are of clinical moment to the individuals concerned"117.(which have been recorded as ranging from) rheumatism to nyctolopia [night blindness]. he proclaimed: "the host's interests demands complete deworming"121. Lane later indicated that the practical import of this view was that the only safe course was to regard no infection as clinically unimportant until such time as the dividing line between hookworm infection and hookworm disease had been defined scientifically 120.195 This view was echoed by Lane (1918). he believed. however. When they analysed changes three months after treatment. Similarly. Boycott in 1911 drew a distinction between Ancylostoma infection and ancylostomiasis. it was not proven that they were unimportant.185 This idea was taken further by Smillie and Augustine (1926) in the USA who divided children up into groups on the basis of hookworm numbers. and more than 500 worms were required for the full clinical disorder to be produced187. Stiles in the USA and Lane in the United Kingdom were the most ardent. at the very least. in a given time. Similarly..Hookworm Disease 517 unimportant is negatived by the fact that treatment of such cases has resulted in the children in question having made greater improvement in certain respects. This information caused Harold Scott in his review of the paper to write: This article is of great interest and serves as a refreshing counterblast to exaggerated records of the dire evils of hookworm infection. he quoted letters from managers of tea estates in Darjeeling.. or that. Not everyone accepted this belief. As late as 1935. physique or mental alertness. in a normal individual. that more recently. Before any proper understanding of hookworm anaemia could be gained. In the same vein and as a result of his own investigations in Argentina. An alternative possibility was canvassed by Rake in 1894: Is the anaemia the result of a simple drain of blood from the gut by worms. it was thought that only a few worms were necessary. He noted that the difficulty with the early Rockefeller reports was that they grouped all grades of infection together. or is it. the question arose as to how the anaemia was produced. made the opinion that any hookworm infestation. The first and most obvious way. DETERMINATION OF THE PATHOGENESIS OF HOOKWORM ANAEMIA Amongst those who accepted that hookworms might cause anaemia. an improvement in haemoglobin concentration only in those with 25-100 worms. practically untenable. and enhanced gains in height. is harmful. Fülleborn declared: One becomes more and more convinced I think. so that improved health and efficiency in a small number of heavily infected individuals might be sufficient to provide the observed improvement in the group as a whole. At one time. with the view being generally upheld that heavy worm burdens were usually required for the production of anaemia. incidence data had been supplemented with information on the intensity of infection. as reported by Griesinger. No doubt even a single hookworm does some injury to its host. fortunately. the condition had to be differentiated from idiopathic pernicious . they left wounds behind them which continued to bleed. as William Hunter contends. is so easily compensated that it is of little or no consequence. the result of excess blood destruction in the portal circulation effected by the action of certain poisonous agents absorbed from the gut through breaches made by the worms?172 The likely importance of this latter mechanism seemed to be heightened when the authoritative and prestigious Looss declared that the epithelial cells of the small bowel rather than blood provided the food supply of hookworms 140. was as a consequence of massive bleeding into the gut. and this led one anonymous reviewer to write in 1889: "Hence it is easy to understand how a very few may cause fatal anaemia"6. as described in the next section. He remarked.80 Also in 1929. weight and haemoglobin level in those who had more than 100 worms188. however. which brought him to hold the opposite conclusion to Stiles and write: Recent investigations have. for it had been shown that when hookworms moved. that in the past the damage caused by a slight hookworm infection has often been overestimated. Chandler reviewed the evidence. but this injury.518 A History of Human Helminthology intervention in children who had less than 25 worms. however light. at least as far as Necator is concerned.56 It was only with the elucidation of the pathogenesis of hookworm anaemia. that the controversy was resolved. however. Experimental studies by Huart in Leiden. re-emphasized the role of gastrointestinal haemorrhage in the genesis of hookworm anaemia. who watched the behaviour of A. however.Hookworm Disease 519 anaemia. stimulated red cell production and a rise in haemoglobin concentration. that either the intramuscular injection of erythrocytes or the oral administration of iron. The importance of this observation was that the natural history of hookworm anaemia was clearly different from the progressive downhill course of pernicious anaemia. and considered that the haemolysin and anticoagulant factor which had been found in hookworms a short while before by Loeb and Smith135 were of no great import. The vessels of the villi became distended. Boycott was puzzled by the mechanism by which the anaemia was produced. it seemed likely that dietary deficiency and gastrointestinal disturbances were of major aetiological significance 174. braziliense.e. although he qualified this statement by saying that exceptions occurred. for he did not believe it was due to gastrointestinal haemorrhage. and as gastric hypochlorhydria was present frequently. and the oesophageal muscles pumped blood through the gut at the rate of 2-4 pulsations per second. Nevertheless. caninum and A. Holland104 and by Fülleborn and Kikuth in Hamburg. Germany81 in 1919 using dogs infected with A. So was the appearance of the blood film. The role of iron deficiency in the genesis of this anaemia was also supported by Cruz in Argentina. Wells calculated that each A. but eventually attached themselves to the bases of some villi. they were hypochromic). Biggam and Ghalioungui in Egypt found that oral iron corrected hookworm anaemia. caninum in the opened intestine of anaesthetized dogs. and failed to identify a place for haemolysis in the production of the anaemia. thus allowing worms to be expelled gradually and haemoglobin concentrations restored. He recognized (1907) that the degree of anaemia was in general proportional to the number of worms present. This latter comment was based largely upon the improvement often seen when patients were removed from an endemic location. Worms moved around on the mucosa for hours. One of the first persons to investigate hookworm anaemia in detail was Arthur Boycott who studied miners in Cornwall infected with hookworm. caninum wasted nearly 0. whereas in pernicious anaemia the erythrocytes were macrocytic and the colour index was normal36.84 ml of blood a day201. The processes by which haemorrhage occurred were observed in vivo by Wells. even when the patient was still harbouring worms. blood appeared in the mouth of the worm. but that removal of the worms alone produced little or no change in the blood picture30. Rhoads and Castle showed in a study of 150 patients with hookworm anaemia in Puerto Rico. They concluded that since deficient diets were the rule. Boycott emphasized that in hookworm anaemia the red cells were microcytic and that the colour index fell (i. he observed that a rich meat diet or the . The importance of gastrointestinal blood loss was then underlined by three studies reported in 1934. but not liver extract (rich in vitamin B12). and suggested that the frequency with which further infections were acquired may be a more important factor. 520 A History of Human Helminthology administration of large doses of iron prevented the appearance of anaemia61. the pendulum began to swing once more. In the same manner. and considerably higher counts were required in Nigerians who had a much higher daily intake of iron87.71.. Thus.03 ml blood was lost per day for each N. RECOGNITION OF THE CLINICAL FEATURES Classical descriptions of illnesses that were possibly or probably a consequence of hookworm infection were described long before the worms themselves were recognized. anaemia was not seen unless egg counts were greater than 1. This realization led to an increased emphasis on hookworm disease and less on hookworm infection. although more modern opinion favours its association with schistosomiasis101. and the arguments which had been raised over the efficiencies of various concentration techniques for the diagnosis of hookworm infection (see later) became less relevant. In 1957. In most people with a normal or highly nutritious diet. or losses of. Attempts have been made to find evidence of hookworm disease in the Egyptian Papyrus Ebers (c.000 eggs per gram of faeces were necessary before anaemia was seen in Venezuela123.000 per gram in the Gambia199. Nevertheless. but that this was not maintained unless the worms were removed by anthelmintic therapy156. these nutrients. Similarly. americanus. but that 0. As a parenthetical postscript. Further. therefore. By the same token. there was little probability of a significant fall in haemoglobin concentration. duodenale 175. Andrews in the southern USA concluded that hookworm disease was more likely and more severe when worm burdens were high and protein consumption was low3. Roche and his colleagues quantified gastrointestinal blood loss in human hookworm infection by labelling erythrocytes with radioactive chromium then measuring the radioactivity subsequently lost in the faeces.disease which was said to be a chronic disorder of the gastrointestinal tract followed by a disturbance of the circulatory system182.1550 BC)162. They calculated that approximately 0. More than 2. it may be remarked that blood-letting activities of hookworms have even been made use of therapeutically in the treatment of polycythaemia rubra vera45. they showed that a return of haemoglobin level to normal could be achieved with iron alone. particularly in the . and it became generally accepted that the likelihood of anaemia was directly proportional to the worm burden and inversely proportional to the iron and protein intake in the diet. growing children and menstruating or pregnant women were more likely to develop disease with a lower worm burden by virtue of increased demands upon.2 ml was lost for every A. Ebell expressed the opinion in his translation of the Papyrus Ebers that the anaemia mentioned .169. Napier and his colleagues in India a few years later considered that even a heavy load of worms did not produce anaemia unless the diet was deficient in iron. becomes a dirty pale yellow. his lips being pale and his tongue white. Gothard Tunnel in 188047.. Thus. you may know him to labour under that disorder which the French call mal d'estomac and the English after them by the same name or 'dirt-eating' from the propensity which there is in that case to eat chalk or clay or some other kind of dirty substance.. cool...... The same clinical manifestations were then described by Wucherer204. Hippocrates (c.. when he is short-breathed and unable to ascend a hill without stopping.. yellow or green-white.5 As mentioned earlier.57..(In) the chronic form.206. the intensity of which we have never seen before. and so much indisposed to motion as to require to be impelled to it by threats. In 1878. .. Various accounts emanating from Central and South America are consistent with a diagnosis of hookworm disease. Griesinger in Egypt was familiar with the syndrome of Egyptian chlorosis before he discovered its relation to hookworm infection. as in the following extract from a book by an anonymous author who was apparently a doctor and a planter: When a negro is languid and listless. a prolonged tachycardia. his efforts for that purpose being accompanied with a throbbing of the temples and a violent palpitation of the heart. when he complains of giddiness. the clinical features of anaemia in association with ancylostomiasis were highlighted in miners working in the St. flabby.. persist in many patients.. and often terminates in dropsy. their skin. the conjunctiva is blue-white...Dyspnea occurs after a few steps ..The pulse is very rapid and weak.This disorder which as I observed is very common in West Indies estates is also one of the most obstinate and troublesome that negroes are afflicted with.makes the patient very indolent and apathetic... in these patients.. In 50 BC.At the same time it becomes very withered... a number of whom were anaemic90. it was recognized that the clinical features of severe hookworm disease were those of marked anaemia produced by the mechanisms discussed earlier. the eyelids and other parts.. although this view is not now generally accepted101... dry and scaly.. and slight fatigue on exertion...Hookworm Disease 521 in association with the worm was probably hookworm anaemia72.Palpitations corresponding to the heart beat... Lucretius wrote of the pallor of those who worked in mines.92 Clearly. He wrote that the symptoms and signs of this affliction were simply those of anaemia: The milder stages are characterized by pallor of the skin and the mucosa..develop edema in the lower extremities.. Similarly. In all the larger arteries one hears a blowing sound.The overall condition of the patient must be viewed as a state of advanced anemia or fluid retention.... and the lips and all visible mucous membranes are a deathly pale... the anaemia had become so intense that marked features of congestive cardiac failure had supervened.the patients.. It disables them from effective labour for a considerable time. Marked generalized weakness and fatigue.Patients often suffer from vertigo.. sometimes for years.a tendency to palpitations. de Moura153 and others in South and Central America.. Khalil109 has claimed that Avicenna (981-1037 AD) referred to hookworms. and islanders living on Puerto Rico15. Grassi and his colleagues in Italy published clinical notes on patients with hookworm infection.460-375 BC) may have been dealing with hookworm infection when he spoke of pallor in people who ate dirt100. He found. The gastrointestinal symptoms were also difficult to define because concurrent infections with other gastrointestinal pathogens was so common. subsequent upper respiratory symptoms (but no indication of Löffler's syndrome). it was realized that simple faecal . As the technique became more widely used. Brumpt infected patients with hypertension or polycythaemia with about 400 hookworm larvae and noted an initial dermatitis. an estimated 440 worms were found in the faeces90. only Ancylostoma ova undergoing segmentation will be found. Conflicting accounts were published on growth retardation and mental sluggishness 89. experimental infection with A. embryos and larvae will also be found.see section on the proof of the percutaneous route of infection) was only observed sometimes. then indigestion and diarrhoea. indigestion. GB Grassi. ceylanicum indicated temporary. diluted with any medium. It was not until 1878 that the Italian parasitologists. The abdominal discomfort soon cleared up but the diarrhoea sometimes persisted for a month45. and remarked further: "this diagnostic tool. Similarly. in one patient. and Davaine had publicized it widely in his textbook of 186066. Corrado Parona and Ernesto Parona reported that: the diagnosis of Ancylostoma is very easy.522 A History of Human Helminthology While the clinical features of gross hookworm anaemia were clear. even after the use of anthelmintics. Wucherer in 1866 posed the question as to whether it might not be possible to determine the presence of hookworms during life in order to distinguish hookworm anaemia from the anaemia of "malarial cachexia". If the material is fresh. however. since Ransom (1856) and Davaine (1857) had shown the value of this diagnostic technique in ascariasis. at the microscopic magnification of at least 90 diameters. would not be used very frequently by our colleagues" 204. Migration through the lungs was thought to produce cough.187. This method of diagnosis was likewise taken up with success two years later by Perroncito when he diagnosed Ancylostoma infection in St. To do this rapidly. the other manifestations of infection were rather more obscure. DEVELOPMENT OF DIAGNOSTIC METHODS The diagnosis of ancylostomiasis was first made only post-mortem. it suffices to examine a little feces or vomit. Dermatitis (ground itch . if it is stale.200. It is surprising that neither Wucherer nor any of his contemporaries paid any attention to looking for hookworm eggs in the faeces. Experimental infection with sole hookworm infections. Gothard tunnel miners presenting to Concato's clinic57. but severe. provided some useful information.188. wheezes and hoarseness in some patients10. flatulence and abdominal distension 202.90 Grassi and his colleagues proved the diagnosis in several of their cases by the administration of anthelmintics and the recovery of adult worms. trichuriasis and taeniasis. that thus far he had not been able to locate adult worms in the faeces. even if it were reliable. however. Ficus laurifolia and F. who himself devoted many years to the problem. A number of efforts have been made to develop immunological tests for the diagnosis of hookworm infection. have been largely unrewarding as the diagnosis is made relatively easily by parasitological methods except in prepatent infections. Krause and Crilly reported that barium meal examination revealed alterations in the small bowel mucosal outline which they called a "deficiency pattern"111. an extract of the figs. Hookworm eggs have been seen in human faeces in Brazil dating from 430-3490 BP74. Finally. and Grassi and his colleagues in Italy treated their patients with a . THE SEARCH FOR EFFECTIVE TREATMENT As early as 1866. because of its effectiveness and local availability. The identification of hookworm eggs in the faeces has been used in recent times to confirm the antiquity of hookworm infection. and immunodiagnosis gives no indication of the worm burden. The forceful opinions expressed by some that light infections were of clinical significance generated intensive efforts. the blood eosinophilia in hookworm infection. The various tests designed up to about 1930 have been reviewed by Lane120. Ghedini (1907) found complement fixing antibodies in the serum of patients with hookworm infection82. someone in the near future will undoubtedly report the diagnosis of hookworm infection by the observation of adult worms during duodenoscopy. although this test is not able to differentiate between the species of hookworms. Similarly. The diagnosis is sometimes suggested by radiography. was effective in the treatment of hookworm infection204. glabrata. Later concentration techniques have been described in chapter 9. however. however. Quantitative techniques have permitted counting of the number of eggs in the faeces and this has been widely accepted as providing an index of the worm burden. this drug at one time became the basis of a hookworm control campaign in Venezuela 152. first described by Müller and Rieder in 1891154. is nonspecific and is merely a pointer to the possible presence of infection. In addition. to develop concentration techniques in order to permit detection of such infections.Hookworm Disease 523 smears did not always detect light infections. although there have been a few vocal opponents of this view121. particularly in the first third of this century. Wucherer in Brazil reported that latex d'higueron. Harada and Mori in 1955 described a completely new method of cultivating hookworm larvae on moistened filter paper which they believed was considerably more efficient than flotation methods for detecting infection96. Such efforts. Pirie and colleagues in 1929 reported a skin test for the diagnosis of hookworm infection170. Indeed. as sophisticated gastrointestinal endoscopic facilities become more widely available. The preparation was not generally obtainable in Europe. but a number of investigators found it to be ineffective. then Ernesto Parona at Varese43. but then Bruning began to use it successfully in 190946.167. anthelminthicum. a synthetic organic compound. were investigated by Caius and Mhaskar in a major series of studies . Schüffner in the Dutch East Indies (Indonesia) reported that it was more effective than thymol. and eucalyptuschloroform-castor oil mixture removed 38% of worms. Perroncito showed that an extract of filix mas killed larvae in vitro within five to ten minutes. and an analysis of the results revealed that male fern was ineffective. prepared from Chenopodium ambrosioides var. betanaphthol expelled 64%. claimed that the well-known remedy for tapeworm infection.524 A History of Human Helminthology combination of santonin. was used by Bentley in 190429. and eventually fell into disrepute. Meanwhile. Perroncito in Turin26.40 with the consequence that the drug became very popular for the next several decades. Baumler (1881) and Breton (1905) had tried it without success for ancylostomiasis. Betanaphthol. while male fern came a poor last183. and that thymol and betanaphthol were about equally efficacious16. jalap and sugar with a modicum of success90. oil of chenopodium eliminated 92% of hookworms. and occasionally death. Unfortunately. Italy. Gothard epidemic provided him with an opportunity to re-evaluate the drug more intensively. Subsequently. it sometimes caused haemolysis or nephritis. Chloroform had been shown in 1885 to be active against tapeworms when used in combination with a purgative which caused passage of the anaesthetized worms27. had been a common household remedy for ascariasis in that country for many years. Camillo Bozzolo investigated the properties of thymol which is prepared from a large number of plants of the genera Thyme. Eucalyptus oil was a popular remedy for a time. eucalyptus was nauseating. Gothard tunnel around 1880. Herman in 1905 introduced a mixture of eucalyptus oil and chloroform for hookworm infection97 and this enjoyed transient fashionableness. Oil of chenopodium (American wormseed oil).163 . filix mas (oleoresin of Aspidium. He had used it in 1879 in one patient with ancylostomiasis without effect38. thymol dislodged 83%.000 patients were treated with various remedies by the Puerto Rico Commission on hookworm. All of these drugs. Although there were claims from time to time that the drug was toxic and could be fatal. The St. Consequently. betanaphthol or eucalyptus oil. and many more. an indigenous plant in the USA. Origanum and Carum. then reported that he had reduced hookworm numbers in two patients by repeated administration of the drug167. Some 300. Dryopteris filix mas and related species) had antihookworm properties. these were not accepted by Lane in his review of antihookworm agents in 1935121. calomel. male fern) prepared from the powdered rhizomes of the fern. He found that following a single treatment. He increased the dosage and in 1881 claimed to have cured six patients39. Interest in the treatment of hookworm infection was stimulated by the outbreak of ancylostomiasis in miners working in the St. an alkylated derivative of phenol and related to thymol. MC Hall of the US Bureau of Animal Industry published a paper indicating that this agent was a useful anthelmintic in animals93. was effective in ancylostomiasis 114.. in which case it remains unknown whether the individuals so sacrificed should have been treated at all. Nicholls and Hampton gave carbon tetrachloride twice to a condemned murderer then examined the organs after execution one to three weeks later.124. particularly in mass treatment campaigns where it had often not been shown that a particular individual was infected: For carbon tetrachloride. Nevertheless.the fatal dose is [he should have said 'may be'] 1. the same group of workers reported that hexylresorcinol.000 cases in Trinidad and Tobago with little report of illness33. The advantage of tetrachlorethylene over carbon tetrachloride was highlighted when Lamson and his colleagues in 1929 showed in experimental dogs that the hepatic necrosis evident after the latter drug was administered was absent when tetrachlorethylene was used115. Straub and Kouwenaar had 16 deaths and gave up using the 155 drug198. This advised dose has naturally killed a varying proportion of those who have taken it. . This drug was introduced by Hall and Shillinger in 192595. these reports must be viewed with some circumspection. For example. Bishop administered the drug to 25. carbon tetrachloride. while Khalil claimed only one fatal result in 150. was introduced. For example. while the dose advised as effective is 3 c. On the other hand. With great indignation. Considerable differences of opinion then ensued over the safety of the drug.157. carbon tetrachloride was safe157. and its effectiveness was confirmed by Schapiro and Stoll two years later180. but this drug did not find a major place in treatment. Mhaskar in 1922 reviewed the results and concluded that of 54 substances investigated. thymol and betanaphthol were the most effective drugs150.. He then swallowed some of the chemical himself without ill-effect. Lane (1930) condemned its use.. Further..000 treatments 110. it has been freely administered without troubling to discover whether any particular recipient was infected. some workers had sad experiences. tetrachlorethylene. oil of chenopodium. and suggested its use in human hookworm infection94. since there may have been a considerable latent period between the ingestion of carbon tetrachloride and the appearance of liver failure which may have obscured the relationship between the two events. No signs of degeneration were found and they concluded that when given in a single dose. chloroform and tetrachloroethane could cause severe liver disease. In 1931. or twice the fatal dose. It was at this juncture that a new drug. A number of reports soon followed showing that it was effective in human ancylostomiasis 24. Being aware that prolonged use of fat solvents such as carbon tetrachloride.Hookworm Disease 525 carried out in India50. while Nag reported three deaths in 289 children .5 c. The drug became used widely and was employed with apparently few side-effects by some workers.. In 1921.119 Carbon tetrachloride was soon followed by its relative.c.cm. The next major advance did not take place until 1958.526 A History of Human Helminthology The merits and demerits of the various anthelmintics known at this time led to contrasting views on the drug of choice in the treatment of hookworm infection. iron therapy alone was often adequate. As has already been indicated in the review of the pathogenesis of hookworm anaemia. many subsequent studies confirmed the value of treating hookworm anaemia with iron as well as giving anthelmintic therapy30. Lane (1935) damned carbon tetrachloride and extolled the virtues of thymol121. bephenium hydroxynaphthoate. One of these. Furthermore. thiabendazole44. More recently. pigs and horses. this was most desirable in the most anaemic patients. particularly men. and showed that the addition of iron preparations hastened the recovery from anaemia after anthelmintic administration 67. An anonymous writer in The Lancet concurred with this view: . In 1961. then many subsequent workers confirmed the effectiveness of the drug. Bui Quoc Huong and colleagues reported that thiabendazole cured 85% of humans infected with hookworm49. it had the added advantages of less toxicity and some activity against Ascaris lumbricoides 88. Brown and his colleagues described a new benzimidazole derivative. pyrantel pamoate was active against mature and immature nematodes in animals20. and before the mechanism of hookworm anaemia was defined and the biochemistry of anaemia due to blood loss was understood. Day reviewed his experience in treating over 300 patients with gross hookworm anaemia (the average haemoglobin concentration was only 22% of normal). Topley concluded that although all hookworms should ideally be eliminated. In 1966. Several years later. As long ago as 1866. Goodwin and his colleagues then showed in a trial in Ceylon that one of these agents. and that for less severely affected persons.174. then a number of authors showed that it eliminated most nematodes from the intestines of sheep. The drug was shown to have an effectiveness comparable with that of tetrachlorethylene. pyrantel embonate was shown to be effective in human ancylostomiasis. with 84% of patients being cured68. In 1914. Wucherer remarked that patients seemed to do better with the combined use of iron preparations and anthelmintics than when anthelmintics alone were given. it was shown that a new series of quaternary ammonium compounds was active against a broad range of nematodes parasitic in laboratory and domestic animals58. In that year. another benzimidazole derivative. Finally. Austin and his colleagues discovered a new series of broad spectrum anthelmintics. The discovery and use of agents directed specifically against hookworms has not been the only way in which the problem of hookworm anaemia has been approached. was also very effective in hookworm infection54.61. These findings were then confirmed by many other workers. while Andrews (1942) espoused carbon tetrachloride and relegated tetrachlorethylene as being less effective3. In the following year. was active in human hookworm infection. Chaia and Cunha in 1971 showed that mebendazole.156. duodenale and N. duodenale was found in the small intestine of a mummified body discovered in Peru and dating from about 900 AD2. It was at first thought that A.13 Such comments as this would have sent shudders up the spine of Stiles and of Lane. whether from hookworm disease in men. but Lombard. even if they did not cause them to turn in their graves. Leiper (1907) confirmed Looss's observations. was able to counter with the reply that a perfectly safe supply of water was piped in164. Bozzolo and Pagliani postulated that impurities in the water used for drinking in the galleries contributed to the spread of hookworm ova. or other causes in women. in addition to being brought over by the early Spaniards. but also in specimens emanating from the Indian subcontinent131 and from Australia. duodenale emanated from the Old World and that N. Furthermore. Thus. keep records. For example. a staunch opponent of the parasitic theory of miner's anaemia. The longstanding presence of A. and distribute tablets. americanus are disseminated widely throughout the tropical world. the parasite may have been indigenous to the Indian race191. Gothard tunnel. all sorts of inexplicable difficulties arose when attempts were made to explain the presence of ancylostomiasis in the St. but they serve to exemplify how far conceptions concerning the management of hookworm infection and disease have swung. Soper (1927) believed that A. but the use of oral iron could increase the economic potential of many populations. and now that iron-deficiency has been shown to be the commonest cause of anaemia among these people. Patients with severe anaemia. americanus was indigenous to the Western Hemisphere. An understanding of the epidemiology of hookworm infection was largely incomprehensible until the percutaneous mode of infection was discovered by Looss around the turn of the present century. finding N. Looss examined some hookworms obtained from six Central African pygmies and found that they were N. americanus not only over wide areas of Africa apart from Egypt. This interest was heightened enormously when the percutaneous . This observation led him to suggest that N. duodenale in South America was supported when an apparent A. The final answer to the problem of hookworm disease probably lies in environmental measures.Hookworm Disease 527 Ferrous sulphate is cheap. UNDERSTANDING THE EPIDEMIOLOGY Both A. duodenale had a much longer history in Central and South America than had been thought and suggested that. In 1905. there seems every reason for training auxiliaries to test for it. and those who did not respond to treatment. could be referred for more definitive treatment. americanus may have been carried to the Americas from Africa by negro slaves140. Nevertheless. americanus. the recurrence of anaemia in miners stimulated interest in observing the habits of hookworm larvae and determining the factors which inhibited or enhanced their development. but their origins are uncertain. creeping up vegetation. and tended to remain in the upper regions of the soil. as this would assist in the development of effective control measures. laws were passed in Belgium compelling the installation of surface waste disposal systems in mines near Liège. and izal were investigated 22. Stiles believed that privies were not only inefficient. and hookworm disease was abolished146. but were concentrated in the neighbourhood of latrines and in constantly damp soil around water storage vessels. Ten years later. thus reducing the chances of infection: "a privy has a radius of influence in every direction of the compass"196. Baermann observed that hookworm larvae wandered from earth into water. In an investigation of hookworm infection in schoolchildren in the USA.35. this new understanding of the mode of transmission improved ideas about the spread of infection in endemic areas. Further. Similar . moist areas under plants or grass survived for at least a month22. carbolic acid. The optimal conditions of temperature. but may have positively evil effects because they concentrated contaminated faeces in focal areas rather than allowing them to be dispersed widely.23. Progressive understanding of all these facts led to the evolution of better preventive and control measures. moving in loose earth at the rate of 1 cm per minute.528 A History of Human Helminthology route of infection was proven. and found that hookworm larvae were not diffused over wide areas. and the actions of various larvicides such as salt. He found that larvae in shaded. Augustine then showed that larvae could migrate laterally for only several centimetres 18. periodic examination and treatment of infected men. He developed a novel method (the Baermann technique) for recovering larvae from soil samples. These observations were then confirmed and extended by Cort and Payne in Trinidad using Baermann's apparatus. A combination of approaches was tried. the percentage of infected miners had fallen from 23% to less than 2%.77. sanitary buckets below ground. but that those who lived in houses where there was a privy were more subject to infection.23. They also found heavy soil infection around "natural latrines" but little evidence of contamination in houses59. decaying wood and other objects as far as the film of moisture allowed19. Stiles (1915) realized that ancylostomiasis was entirely due to bad sanitation and considered its prevalence as an index of the sanitation in the district where it occurred. and instruction in the principles of personal prophylaxis. he found that those children who came from sewered homes were relatively protected. Similarly. In 1904. humidity and oxygen tension necessary for development of larvae were defined. This concept was confirmed by Baermann working in Indonesia (1917). THE EVOLUTION OF PREVENTIVE AND CONTROL MEASURES The first major attempts to control ancylostomiasis were undertaken in infected mines in Europe. Salt was one of the first chemicals suggested for the control of transmission. These results encouraged Rockefeller to consider an extension of the work and scope of the Commission to outside of the USA. or by temporary dispensaries set up especially for that purpose. In 1909. The value of the measure was forgotten and was rediscovered by WO Fischer working in gold mines in the Rand. While methods such as these were successful in localized areas such as mines. Weekly disinfection with salt around underground latrines was adopted and infected miners were given anthelmintics with excellent results12. and stimulated by increasing reports of hookworm infection in the southern United States itself. The first region in which major attempts at control were initiated was the island of Puerto Rico into which the large resources of the United States government were thrown. blighted ambition. South Africa76.53. partial inhibition of physical and mental growth. This idea was reinforced when it was discovered that miners working in salty mines in Poland. but perhaps because of its simplicity. 1. great loss of life. The Rockefeller . These people were treated. misery and poverty to health.75 Because of these efforts. there was a noticeable improvement in living conditions. Scattering of salt around mines was recommended 9. In 1880.25 million people were examined and over 690. During the first five years. it was not received with much enthusiasm. Rockefeller gave a million dollars to a Commission of thirteen leading educators.000 were found to be infected. together with the awakening of an intelligent public interest in hygiene and sanitation34. it embarked upon the study and treatment of hookworm disease with considerable reward. and decreased economic efficiency.Hookworm Disease 529 principles were adopted in mines in other parts of Europe. either by local practitioners working in cooperation with the Commission. physicians and business men to be used during the next five years to work towards the eradication of hookworm. The "lazy niggers" and "poor white trash" of the South were found in reality to be the unsuspecting victims of this insidious infection which sapped their strength and vitality. Encouraged by Ashford's success. The twin planks upon which the campaign was to be based were the installation of sanitary privies for all people in infected areas and by the treatment of every infected person. completely different approaches were needed in the massive endemic areas of the tropics. Perroncito showed that salt was toxic to Ancylostoma larvae. A commission headed by BK Ashford was set up in 1904. The Commission believed that hookworm produced vast suffering. France and Cornwall were protected from infection. happiness and productive activity does the teaching which excites them to action. In 1913. Charles Stiles persuaded John D Rockefeller to finance the organization of a Sanitary Commission to eradicate hookworm disease in that area. The results of the campaign were eulogized: The witnessing by the people of the transformation from invalidism. Investigations in later years showed that hookworm larvae easily penetrated wet canvas footwear. without wasting time.65. Further. Egypt. The Foundation worked through.11 The validity of proper sanitary measures had been well shown in several studies. and cooperated with. and whose use was supervised. Darling asserted that it was sufficient to remove most of the worms from a patient. albeit at lower intensities of infection. evidence began to accumulate that hookworm infection reappeared in populations which had undergone mass treatment. with some members of the Board. Two basic approaches were adopted. This was in turn modified at times. together with surveys of infection and sanitation. and as many anticipated. The first countries to be tackled were some of the West Indian islands. The use of footwear and other agents to protect the skin as a prophylactic against hookworm infection has given conflicting results. This was replaced progressively. campaigns were being carried out on a more or less extensive scale in the majority of infected countries in the world.530 A History of Human Helminthology Foundation was formed and its International Health Commission. This extension was first begun in 1914 in certain countries of the British Empire where the stability of government and the official use of English facilitated work. British Guiana.186. ventilated. at least initially98. until by the middle of the 1920's. The logical inference was that mass treatment had to be accompanied by effective sanitary measures: Mass treatment without coincidental soil sanitation is likened to bailing a sieve-bottomed boat. The Commission then moved into Central American countries. however. Manson in 1904 recalled how a West Indian sugar planter had his coolies dip their feet in a mineral oil tar coated with sand. by the "Intensive Method" whereby a defined area was examined systematically. Brazil and China. urging mass treatment of heavily infected populations without first verifying the diagnosis in individual persons. funds. Unfortunately. The "Dispensary Method" consisted of the examination and treatment of people who presented themselves. and attempts were made to improve general sanitation103. such as Darling. Ceylon and Malaya. and began on a small scale in order to develop the most appropriate strategy for that country. or generating toxicity by attempting to achieve total eradication 64. universal use of a sanitary latrine constituting the only hope of eradicating the infection. later International Health Board. The overall mortality (to which hookworm was thought to be a major contributor) fell over ten years from 40 per thousand to 4 per thousand of population 23. Perhaps the most impressive of these was that of Baermann who built well-constructed. the whole population was tested. undertook to become involved in hookworm control campaigns in other countries. all those found infected were treated. governmental bodies in the countries concerned. but Dalgetty pointed out the difficulties of such arrangements 63. clean latrines in the Dutch East Indies. and most observers were not impressed with the results of wearing the shoes that were commonly available in most . as yet dim. Uncinariasis (hookworm disease) in Porto Rico. 1934 13. Hookworms in gold-mines. Annals of Internal Medicine 17: 891-901. Lancet i: 1883. Nature 212: 1272-1274. a new anthelmintic effective against infections of domestic animals. Lancet i: 766. New methods of hookworm disease investigation and control. GERSZTEN E. 1911 17. 1918. On the management of Negro slaves. 1922 20. ANONYMOUS. Archivos Brasileiros de . Senate Document 808. ANONYMOUS. ANONYMOUS. ALLISON MJ. pp 335. Abstracted in Tropical Diseases Bulletin 15: 224. American Journal of Hygiene 2: 162-171. ANDREWS J. AUSTIN WC. ATTYGALE.Hookworm Disease 531 endemic areas. did claim that the prevalence of infection was diminished in a village where a cheap kind of footwear made from old rubber tyres was used when compared with a neighbouring village in which this was not the practice1. Cairo 1: 4-12. MORGAN DH. GUTIERREZ-IGARAVÍDEZ P. HASEGAWA I. Washington. 1905 10. AUGUSTINE DL. 1889 7. is the development and deployment of a powerful and durable vaccine. PEZZIA A. ANONYMOUS. ANONYMOUS. COURTNEY W. 1966 21. British Medical Journal ii: 807-808. Cited in 120. 1920 11. Modern views on the treatment and prevention of hookworm disease. however. 1922 19. ASHFORD BK. Ankylostomiasis in Puerto Rico. 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United States Public Health and Marine Hospital Service.538 A History of Human Helminthology der Medizin 6: 12-20. Rendiconti del Reale Istituto Lombardo di Scienze e Lettere. SCOTT HH. Die Krankheiten des Orient's vom Standpunkte der vergleichendin Nosologie betrachtet. 1901 178. RAKE B. ROGERS L. Milan. 1894 173. 1923 187. SONSINO P. SISCO DL. British Medical Journal ii: 690-691. series 2. Palme und Enke. Journal of the American Medical Association 80: 451-454. 1886 185. 1902 193. Study of urinary and fecal excretion of radioactive chromium Cr51 in Man. RETIEF F. American Medicine 3: 777-778. 1890 191. STOLL NR. Cross-breeding experiments in Ancylostoma braziliense de Faria. 1911. Noch ein Wort über Ankylostoma duodenale. Its use in the measurement of intestinal blood loss associated with hookworm infection. SMITH AJ. 1926 186. Southern Medical Journal 19: 19-28. The report of a nearly pure Ancylostoma duodenale infestation in native South American Indians and a discussion of its ethnological significance. The debate on ankylostomiasis: a correction. American Journal of Tropical Medicine 7: 193-198. DC. Cited in 56 190. 1900 177. SMILLIE WG. The effect of varying intensities on the physical condition of school children. SCHÜFFNER W. 1847 172. SCHEUTHAUER G. Beiträge zur Erklärung des Papyrus Ebers. 1927 181. Annotazioni critiche sull'anchilostoma duodenale. 1968 174. Archiv für pathologische Anatomie und Physiologie und für klinische Medicin (R Virchow) 85:343-354. PRUNER. AUGUSTINE DL. Der Wert einiger Vermifuga gegenüber dem Ankylostomum mit Bemerkungen über die Wurmkrankheit in Niederländisch-Indien. Deutsche medizinische Wochenschrift 30: 1338-1339.und Tropen-Hygiene 16: 569-588. Skin reactions in ankylostomiasis. SANDWITH FM. Lancet i: 255. 1926 188. The American hookworm (Necator americanus) in Guam and China. Ankylostomiasis and beri-beri. 2: 460-467. LAYRISSE M. VETTER JC. pp 472. pp 121. AUGUSTINE DL. 1927 192. di PRISCO E. British Medical Journal i: 289. PIRIE JH. STILES CW. Johns Hopkins Hospital Bulletin 17: 313. American Journal of Diseases of Children 31: 151-168. REP BH. Hookworm. 1905 179. SANGALLI G. Hygienic Laboratory Bulletin No. SMILLIE WG. SOPER FL. Preliminary note on the anthelmintic value of tetrachlorethylene based on egg counts before and after one treatment. 1903 194. Extracts from an inaugural address on the opportunities for research in Trinidad. Erlangen. SCHAPIRO L. Note on the entrance of Ankylostoma embryos into the human body by means of the skin. Lancet i: 435-436. Report upon the prevalence and geographic distribution of hookworm disease in the United States. FERGUSON AL. American Journal of Hygiene 7: 174-184. STILES CW. Archiv für Schiffs. Observations on the etiology and treatment of the anemia of hookworm disease in Porto Rico. ROCHE M. Hookworm infestation. Berliner klinische Wochenschrift 20: 797-800. Proceedings of the Transvaal Mine Medical Officers' Association 9: 19-20. CASTLE WB. Journal of Clinical Investigation 36: 1183-1192. 1904 182. 1932 (Abstract) 175. Ueber die Einwanderung der Ankylostomum-larven von der Haut aus. SCHULTHESS W. 1926 189. ceylanicum Looss. RHOADS CP. 1910 and A. 1881 183. 1868 206. New York Medical Journal 102: 906-907. 1931 202. STILES CW. STRAUB M. Hookworm anaemia among men. 1895 204. Anchylostomos duodenaes. ZINN W. STILES CW. Geneeskundig Tijdschrift voor Nederlandsch-Indië 65: 624-645. Transactions of the Royal Society of Tropical Medicine and Hygiene 62: 579-594. Publication No. JACOBY MJ. Early symptoms after experimental infection of man with Ancylostoma braziliense var. 1872 207. WIJERS DJ. On the oral infection by hookworm. WUCHERER OE. Medical Journal of Australia i: 1-7. nebst weiteren Beiträgen zur Fauna des Negerdarmes. The Rockefeller Sanitary Commission for the Eradication of Hookworm Disease. NEILSON IL. American Journal of Hygiene 3: 156-179.und Tropen-Hygiene30: 663-679. 52-54. Journal of Parasitology 17: 167-182. WAITE JH. Tetrachloorkoulstofvergiftiging in twaalf gevallen. 1866. Ueber das regelmäsige Vorkommen von Anchylostomum duodenale ohne secundäre Anämie bei Negern. 241 and 243. A study of the effects of hookworm infection upon the mental development of north Queensland school children. TOPLEY E. 1925. WUCHERER OE. Archiv für Schiffs. YOKOGAWA S. WELLS HS. Common anaemias in rural Gambia. New York. Tropical and Geographical Medicine 18: 48-52. 1919 201. On oral infection with Ankylostoma.Hookworm Disease 539 195. Partly translated in 107 205. WUCHERER OE. STOLL NR. Gazeta Medica da Bahia 1: 27-29. OISO T. with English summary 208. Observations on the blood sucking activities of the hookworm Ancylostoma caninum. 1896 . Lancet i: 192. 1966 203. 1915 197. Sobre a molestia vulgarmente denominada oppilação ou cançaço. 2. 1923 198. On the prevalence of Ankylostomum duodenale in Madras. Also. 1925 199.) Taiwan Igakkai Zasshi Nos. SMIT AM. WILLIAMS CH. 1914 196. In Japanese. 1968 200. Berliner klinische Wochenschrift 33: 797-801. 39-41. 1926. 63-64. On the relation between the number of eggs found in human feces and the number of hookworms in the host. Gazeta Medica da Bahia ii: 150-151. Deutsches Archiv für klinische Medicin 10: 379-400. tropische Chlorose oder tropische Hypoämie. Report of the scientific secretary. Ueber die Anchylostomenkrankheit. (Investigations on the life history of Ankylostoma and Strongyloides stercoralis. ceylanicum. Recent studies on school children. with special reference to hookworm disease and sanitation. YOKOGAWA S. 1. duodenale but did not publicize the observation Grassi.540 A History of Human Helminthology Table 20. ceylanicum recovered from a civet cat by Willey in Sri Lanka (Ceylon) Looss reported the development of a patent infection in a person 71 days after percutaneous exposure Lane found humans infected with A. Parona and Parona described the in vitro development of hookworm ova and larvae and showed that infection could be diagnosed by finding eggs in faeces Outbreak of hookworm anaemia in miners building the St. americanus Looss described the migratory course throught the lungs of infective larvae in dogs Boycott differentiated microcytic hookworm anaemia from the macrocytic anaemia produced by Diphyllobothrium latum Bruning reported that oil of chenopodium was effective in treatment John D Rockefeller established a Sanitary Commission to control hookworm infection in the United States of America Looss described A. Gothard tunnel in the Italian Alps Parona showed that filix mas (male fern) was effective in treatment Bozzolo showed that thymol was effective in treatment Leichtenstern observed patent infections in humans 4-5 weeks after ingestion of infective larvae Looss first suggested that infection may be acquired by percutaneous penetration by larvae Looss demonstrated histologically the penetration of intact human skin by infective larvae Bentley described hookworm infective larvae as the cause of "ground-itch" Stiles described the morphological distinctiveness of N. Landmarks in hookworm disease __________________________________________________________________ 1838 1852-54 1866 1868 1878 Dubini discovered the adult worm Bilharz/Griesinger proposed that hookworm was the cause of "Egyptian chlorosis" (gross anaemia) Wucherer indicated that latex d'higueron (fig extract in South America) was an effective treatment Camuset appreciated that hookworm in the Americas differed morphologically from A. ceylanicum The Rockefeller International Health Commission (later Board) began hookworm control campaigns in countries outside the USA Hall introduced treatment with carbon tetrachloride Hall and Shillinger introduced treatment with tetrachlorethylene Experimental studies emphasized the role of gastrointestinal bleeding in the genesis of hookworm anaemia Anumber of investigations showed clearly the role of iron deficiency in the causation of hookworm anaemia Bephenium hydroxynaphthoate was shown to be an effective treatment by Goodwin and his colleagues 1880 1880 1881 1886 1898 1901 1901 1902 1905 1907 1909 1909 1910 1911 1913 1913 1921 1925 1929 1935 1958 . Hookworm Disease 1962 541 Bui Quoc Hong and his colleagues reported that thiabendazole was an effective treatment 1970 Pyrantel was found by Desowitz and co-workers to be an effective antihookworm agent 1971 Chaia and Cunha observed that mebendazole was highly active against hookworm __________________________________________________________________ . . abdominal pain. cats Major clinical features: urticaria. many French troops who had bee n posted to Cochin China (Vietnam) were afflicted with severe diarrhoea which was sometimes fatal. pruritus ani Diagnosis: finding larvae in faeces or duodenal fluid. rhabditiform larvae released in the bowel lumen may moult to form filariform larvae and penetrate the colonic mucosa to continue the cycle (internal autoinfection) or penetrate the perianal skin to continue the cycle (external autoinfection). physician to th e Naval Hospital of St Mandrier in Toulon. Finally. When he examined 543 . massive infection with widespread dissemination of larvae may supervene in immunosuppressed persons Definitive hosts: humans. live in the epithelial layer of the small intestine. either moult twice to form third-stage (infective or filariform) larvae (the direct cycle) or moult four times to become free-living male and female adult worms which in turn produce eggs which hatch to form rhabditiform larvae which moult twice to form filariform larvae (the indirect cycle). ascend the airways to the pharynx. especially in the tropics and subtropics Life cycle: The parthenogenetic female adult worms. In addition. 2. Rhabdonema strongyloides. and are swallowed and pass to the small bowel where they mature over one month or so. diarrhoea. dogs. First-stage (rhabditiform) larvae are passed in the faeces then. a number of patients were repatriated t o France where they came under the care of Louis Normand.5 mm in length. on other occasions worms were present in prodigious numbers with a million or so being excreted during the course of 24 hours. being about one quarter of a millimetre in length. Infective larvae penetrate the intact skin and pass via the bloodstream to the lungs where they enter the alveolar spaces. Rhabditis stercoralis. Normand examined the faeces o f these patients and in some of them he found specimens of a worm which had never been described before. The parasite was just visible to the naked eye . intestinalis. A. weight loss. Strongyloides intestinalis Distribution: widespread. cambendazole. serology Treatment: thiabendazole (mebendazole. In July 1876. in the external environment.Chapter 21 RETURN TO Strongyloides stercoralis and STRONGYLOIDIASIS SYNOPSIS Major synonyms: Anguillula stercoralis. albendazole) DISCOVERY OF LARVAL AND ADULT WORMS AND DETERMINATION OF THEIR RELATIONSHIP In the latter part of the ninteenth century. Although they were ofte n sparse. he observed individual worms which were sometimes caught in a clump of epithelial cells. both names being derived from the latin words "anguilla" meaning "eel". The male worms. P Gervais presented Bavay's more detailed description of the worm to the Academy6. and indicated that he believed that the differences did not justify the creation of a new genus. had noted that Bavay had already called the parasite Anguillula stercoralis. He noted that the eggs on deposition containe d well-formed. in his first paper. Normand occasionally saw a large number of worms squirming about in an almost transparent mass as if they were trying to escape from an enclosing membrane. In this publication. Normand entrusted the worms to the care of his colleague. He summarized the important differential characteristics which justified its description as a separate species: In summary. Nevertheless. professor of pharmacy in the Navy . however. Jurien de la Gravière. and "stercus" denoting "dung".3 3 mm in length by 0.544 A History of Human Helminthology faecal samples with a microscope. while in two subsequent papers he referred to it as Anguillula stercoralis "Du sous-genre [of the subgenus] Rhabditis. Bavay made a number of observations on this parasite and in October 1876. 0. in the original presentation of Normand's discovery. this nematode. motile embryos and that the young forms had sometimes actually broken out of the egg-shell while still within the uterus. If thes e larvae were left under favourable conditions in vitro. Rhabditis terricola of Dujardin or the genus Leptodera of Schneider. I searched in vain for this parasite in other patients afflicted with analogous symptoms but their afflictions apparently came from other sources. Meanwhile. were smaller than the female helminths. This name reflected the eel-like shape of the worm as well as the discovery of the parasite in the faeces. uterus and vulva..8.differs in its invariably smaller size. which is very similar to the Rhabditis terricola of Dujardin. but specially in the shape of the penile apparatus. intestine. Bavay discovered that they developed into male and female adult worms after fiv e days or so. on the other hand. ou [or] Leptodera Schneider" 7. that were found in the faeces. Bavay called the parasite both Anguillula stercorale and Rhabditis stercoralis 6.022 mm in width.. Bavay noted that the forms usually met by clinicians were the larvae. He wrote that the free-living femal e worms were 1 mm in length and cylindrical in shape. however. oesophagus. a parasite is found which has never been found before under similar circumstances. then described the morphology of the mouth.81 The Admiral in turn transmitted extracts of Normand's report together with a resumé of Normand's findings to the President of the Academy of Science s where it was presented and published on 31 July 1876 81.6 . I can prove that from time to time and most often in serious cases. Bavay remarked that the wor m resembled the free-living worm. Bavay described th e anatomy of the male reproductive organs and stated that he had sometimes seen male and female worms in copula. At other times. ARJB Bavay.. Normand reported his discovery to Vice-Admiral Jurien de la Gravière: Today in regard to the disease called diarrhea of Cochin China. however. each one contained a distinct. In early 1977. Chastang17 and Chauvin18 who found the worms in patients that had been infected in China or in Martinique. the situation had become somewhat more confused. then moulted. and did not reach the ileum. however. the released larva was about 0. which appeared to be different from A. less common in the jejunum. Bavay recorde d that he and Normand had found a new type of larva which they believed was the larval form of A. these authors did not observe the maturation of larvae to adult worms in the stools. stercoralis at autopsy in the stomach and the whole length of the intestine. the n developed a jagged border which gave them the appearance of a chain-saw . apparently . naming it A. but that in any case. In the meantime. he had foun d larvae which matched those d escribed by Bavay 66 in the intestines. Like Bavay. on the contrary.Strongyloidiasis 545 In an addendum to this paper. with a cylindrical oesophagus which passed almost to the middle of the body. Shortly thereafter. Bavay noted that Normand had found that they were most abundant in the duodenum. stercoralis.1 mm in length. Laveran was followed by Libermann72. Verification of Normand's discovery did not take long in coming. they contained certain larvae that were different from the first. then shortly afterwards he reported finding four more such cases 67. and a tail. motile embryo within a membrane. pancreatic and hepatic ducts and in the gal l bladder6. B avay published a description of the parasite in February 1877. In addition to describing this parasitic female adult worm. they were much less frequent than A.2 mm in length and all of the 200 specimens or so that he examine d were female. Bavay reported that Normand had now found the larvae of A. Again through the agency of M Gervais. Alphonse Laveran (the discoverer of malarial parasites) reported that. He sent these worms to Bavay. Normand also described the development of free-livin g adult worms from larvae in faeces then observed the course of events whic h occurred after eggs were liberated b y free-living female worms. he observed that when eggs were expelled. In late 1876. nor did Bavay have any such success 6. They were longer.3 mm long. These worms were about 2. at an autopsy he performed on 28 January 1877. stercoralis. at the autopsy of a man who had died from Cochin-Chin a diarrhoea. intestinalis: In the stools of three diarrhoeic patients that we have kept in order to follow the development of Anguillula stercoralis. eve n though there was scepticism on the part of some and incredulity on the part of others. Normand. With the exception of Chauvin. to obtain a second generation of free-living worms 82. which instead of terminating in a fine point. in the intestines. These grew gradually to about 0. we have found that after several days. intestinalis in order to reflect its discovery in the intestinal tract 7. The latter studied them and those that were obtained from a further four post-morte m examinations and concluded that they were a distinct species of worm. found another worm. After each egg had hatched. was. as well as in the bile. Roux95 . Normand was unable. 75 mm long with an oesophagus occupying half the length of the worm. they observed that these larvae in the small intestinal lumen were identical with those excreted in the faeces and these in turn appeared to be the same as the larvae described as A. In 1879. Similar worms were noted in the following year by Chauvin 18. stercoralis. Gothard tunnel (see chapter 20) 88. At no time did Grassi and Parona grow any of the free-living adult worms which other workers had obtained when A. stercoralis was extremely abundant. In the instance of A. Grassi and Parona discovered A. Both the adult and larva l forms of the parasite were illustrate d by Bavay in a publication which appeared in July 18778. ( [STRONGYLOS] = "round" . intestinalis. stercoralis by Normand and Bavay. they observed that th e parasitic worms were located principally in the lower duodenum and uppe r jejunum. [EIDOS] = "similar") because of its closeness to the genus Strongylus. Although culture of these larvae could not be persisted with long enough to establish in an irrefutable fashion their identity with Anguillula intestinalis. Chauvin. intestinalis. intestinalis. the sequence of events seemed to be that parasitic female worms ( A. Eduardo Perroncito drew attention to the presence o f these parasites. he and Normand had looked in vain for these worms in the body of a man who had returned from Cochin-China three years before and in whom A.546 A History of Human Helminthology truncated. In 1878. as well as Ancylostoma duodenale . Grassi and Parona realized that these worms (now known as infective or filariform larvae) wer e undoubtedly the same forms that Bavay. Italy 49. which in turn developed int o filariform larvae in the free-living state. Thus. in the intestinal tract o f miners working in the St. he . and after him. Thus. When m oistened faeces containing these larvae were cultured. it was believe d that there were two distinct species. we have hardly any doubt in this regard. Like Normand and Bavay. then later in that year in a review of his ow n article. Moreover. the worms grew into forms about 0. Grassi erected a new genus which he called Strongyloides. had believed were the larvae of A. Further. Although he did not realize it.7 Bavay went on to say that two of the patients who had had this form in thei r stools had since died. larvae were found in the faeces and adult worm s developed in the external environment. parasitic female adult worms were found in the gut. Initially. intestinalis) produced larvae (now known as rhabditiform larvae because of the similarity of the oesophagus with tha t seen in the genus Rhadbitis) in the intestine. at this point. They found that these worms deposited eggs in the intestinal lumen which hatched almost immediately after being laid. In the case of A. he indicated that the worm should be called Strongyloides intestinalis 44. and that post mortem examination had revealed adult A. and they were thought to produce larvae with the truncated tail. Bavay had described the direc t development of larvae excreted in the faeces into infective (filariform) larvae. Shortly afterwards. in which to place the worm 43. intestinalis at a number of autopsies in Pavla. stercoralis larvae had been cultured. occurred in Gerhardt's clinic at Würzburg. Thus. stercoralis. stercoralis. however. intestinalis whereas Perroncito had demonstrated that they were produced by free-living adul t A. duodenale. and described accurately their copulation. stercoralis. filariform larvae developed from A. stercoralis. Grassi insisted that the rhabditiform larvae found in the faeces were direct descendants of the wor m known as A. and became completely misled in ident ifying "encystment" of both forms of larvae89. intestinalis larvae. and stated that after one day of life they too became encysted. Perroncito persisted in the erroneous differentiation of two species o f Strongyloides. intestinalis and A. then recounted their subsequent development.103. intestinalis. intestinalis eggs were excreted in the faeces. he described the larvae of A. believed incorrectly that A. which was studied by Seifert 102. Perroncito succeeded in cultivatin g free-living adult worms (which h e renamed Pseudorhabditis stercoralis ) from rhabditiform larvae in the faece s. According to Bavay and to Grassi and Parona. He described the development and hatching of the so-called A.Strongyloidiasis 547 believed that both A. Rudolf Leuckart supported this view in the following year when he reported his own observations on the development of A. the hatching of these and the transformation of the second generation of worms into filariform larvae 91. described some non-exi stent morphological differences between the larvae. H e believed that when these escaped in the faeces. He found that after 24 hours the y doubled their length and underwent internal reorganization. The faeces contained large numbers of rhabditiform larvae typical . intestinalis and A. Subsequently (1881). Similarly. As with A. A case of strongyloidiasis. he meant that the parasitic worm in the intestines was parthenogenetic o r hermaphroditic and produced eggs which hatched rhabditiform larvae. Furthermore. The situation was now very confused for filariform larvae had been described as developing in two ways. Perroncito's assertion that A. with the former appearing in the faeces as eggs. they developed into sexuall y differentiated free-living male and female adult worms which in turn produced descendants that were capable of develop ing again into parasitic mother worms after ingestion by the host. Perroncito misinterpreted the moulting process as cyst formation. stercoralis were present. and described subsequent calcification of the capsule. intestinalis.92. the laying of new eggs. he postulated in 1882 that as thes e larvae often developed in culture into freeliving adults called A. intestinalis eggs. and the latter as larvae. like Ascaris nigrovenosa was dimorphobiotic 45. duodenale. By this. intestinalis eggs were excreted in the faeces led to a spirited controversy with Grassi who eventually proved beyond doubt that Perroncito had been dealing with hookworm eggs 45-48. indicated some differences from the larvae of A. then A. particularly with respect to the anatomy of the alimentary canal. These filariform larvae were very similar to those that Grassi and Parona had described as developing directl y from A. . for the shape of its body and oesophagus resembled strongly that of filariform larvae. some observers 7.e. santonin and thymol and recovered two parasitic females in the faeces and a degenerated specimen from the vomitus. A s already mentioned. intestinalis. whereas others 70. treated the patient who had provi ded the faeces with male fern.70 Evidence supporting this view was provided when Seifert. in fact. that there was an alternation between parasitic and free-living generations of adult worms. and that the new embryos developing from the eggs produced by these worms metamorphosed into filariform larvae. The firs t concerned the development of filariform larvae and the second related t o whether the parasitic worms were hermaphroditic or parthenogenetic.548 A History of Human Helminthology of those described by Normand and Bavay and by Perroncito as A. the making of the preparations etc. Grassi (1883) once more drew attention to this capacity o f . seemed interested only in the fate of the sexual animals and I myself as yet understood but little of the purport of the investigations. developing externally. and as A.103. Leuckart was convinced that these filariform larve must pas s into another host in order to complete their development. they developed into free-living male and femal e A. He considered that all these worms were but different phases of the life cycle of a single heterogonic parasite i.. 75 Nevertheless. In the latter. He considered that th e mature stage of these larvae wa s undoubtedly the parasitic adult A. like the Rhabditis ascaridis nigrovenosa. Arthur Looss.took part in these investigations in the sense that Leuckart entrusted me with the starting and controlling of the cultures. stercoralis. . despite its sexual differentiation. for both modes of development were observed in his laboratory in the same faecal specimens. a good many unmistakable filariform larvae were found even at a time when sexual animals were not yet mature. not the cultures themselves.91 had described their production from larvae liberated by free. who at the time had been a student o f Leuckart. In an illuminating insight into Leuckart's research an d teaching methods. stercoralis was ever observed in the stools 102. I did not specially report the direct transformation of the larvae to my teacher and the fact of its existence remained unknown to him. intestinalis by Grassi and Parona on the other . and so far as I can remember personally examined only the finished preparations. Leuckart.living adult worms. however.49 had noted direct development o f filariform larvae in faeces. it represents. an intermediate generation. Leuckart renamed th e parasite Rhabdonema strongyloides 70 and concluded that: The Rhabditis stercoralis itself is to be erased from the list of essential parasites.8. although he wa s unaware of the event. Seifert sent samples of the faeces to Leuckart in Leipzig who reported tha t when these were cultured. as it then appeared to me. stercoralis on the one hand. should have been in a position to resolve this prob lem. whereas no sexually diffferentiated adult A. which forms a link in the chain of development of the Anguillula intestinalis. Two important questions remained unanswered. for their structure was su ch that he did not believe that they could possibly change again into the rhabditiform form. Since Leuckart. recounted nearly 30 years later the circumstances: I.. at the suggestion of Grassi.18. however. On the other hand.. or whether the worms were hermaphroditic with a female habitus 8. primates and a dog) in forty dogs and declared that filariform larvae developed into "pre-adolescent" and adul t male and female worms in the respiratory tract.. Uncertainty also surrounded the status of the parasitic adult worms found in the intestinal tract. This view was echoed later by Leichtenster n who studied over many years cases of strongyloidiasis occurring in brick workers along the Rhine. In 1888. Bavay questioned whether the absence of male worms was due to their rapid disappearance following fertilization.29 Faust then proceeded to compound the problem. He then suggested that strains of temperate origin developed directly whereas those acquired in the tropic s tended to develop indirectly69. In 1884. He traced the development of twelve strains of S. as well as indirect development of others through the free-living sexually differentiated generation: they believed the forme r course to be the commoner 40. The proble m became even more controversial when in 1932 Kreis in Faust's laboratory in New Orleans claimed to have found parasitic male adult worms in the faeces of infected humans and dogs 61. Faust endorsed the view remarking: occasionally parasitic females and males are passed in diarrheic stools. Leuckart concurred with these two last possibilities. That these different courses were not due to two different strains of the worm was shown by Wilm s in Leichtenstern's laboratory. as well as cases imported from the tropics. Fertilization was then believed to take place either there or in the lumen of the upper alimentary canal before the fertilized females became embedded in the intestinal mucosa. Leichtenstern's suggestion of geographica l variations in the form of free-living development was also not sustained when Darling working in Panama 22 and later Sandground in Honduras 97 found both modes of development with the indirect cycle predominating in the experience of the former observer and direct transformation being most common in th e hands of the latter investigator. inclined to the view that they were hermaphroditic 70.. stercoralis (from humans. He furthe r proposed that fertilized eggs proceeded to direct development and unfertilized .The rare parasitic males are practically indistinguishable from the free-living males of the indirect cycle.41. Golgi and Monti in Pavia studied further cases and followed both the direc t transformation of some rhabditiform larvae obtained from parasitic femal e worms into filariform larvae. however. and while expressing no fir m opinion. Grass i suggested that they may be hermaphroditic or parthenogenetic 45. He tried to vary the proportion of worms developing in each direction by altering th e environmental conditions but failed to do so 68. Sandground (1926) believed that the parasitic adult worm wa s really hermaphroditic 98 but this view has not been sustained. Shortly afterwards.71.Strongyloidiasis 549 rhabditiform larvae to develop directly into filariform larvae 46. Rovelli concluded that the worms were parthenogenetic 96. for he infected a human with filariform larvae which had developed directl y then showed that some of the rhabditiform larvae subsequently excreted in the stools developed indirectly 119. Others. stercoralis larvae in the stools of patients with Cochin-China diarrhoea. In fact. The only possible conclusions from thi s observation were that the worm was either parthenogenetic or hermaphroditic. however. Graham succeeded in producing patent infections in rats exposed to a single S. ratti filariform larva each 42. A number of early observers including Laveran 66. no other investigators were able to find such worms and the concept fell into disrepute. not only in the depths of the lumen of the .44 were less certain. Since the generic nam e Anguillula was already occupied for species of eel. and detailed anatomical studies of the parasite since that time have confirmed the former proposition. Grassi found the parasite in the stools of so many apparently healthy individuals that he eventually asserted that thes e worms were innocent commensals of man 47. intestinalis was realized. Although Faust continued to describe the parasitic male in his textbook as late as 1970 32. including Libermann 72. Golgi and Monti at autopsy (1884) found intestinal changes with worms in the crypts of Lieberkühn 40. however. Chastang 17 Breton14 and Grassi43. intestinalis. it became necessary to use the same name for both species. Indeed. but this was disproven when eradication with anthelmintics of hookworms but not S. stercoralis larvae7. he asked in a rhetorical question whethe r these worms were pathogenic and concluded that it was premature to say that they were. however. the designation Strongyloides intestinalis suggested by Grassi in 1879 was generally accepted. Stiles and Hassall considered that the correct name should be Strongyloides stercoralis 110. When the identity of A. CORRELATION OF INFECTION WITH PATHOLOGY When Normand reported the presence of A. however. stercoralis had been described before A. for these worms were present in such small numbers when com pared with the frequency of A. then Sonsino (1891) discovered eggs and larvae.41. intestinalis) in the gut.83. but also noted that worms could be present withou t producing ill-effects82. Gothard tunnel 88.67. When Bavay published the discovery of a secon d worm (A. although he w as careful to add the proviso that there were other causes of a similar condition 81. As S. in 1936 . stercoralis larvae cured the anaemia. stercoralis was a potent cause of diarrhoea. Subsequent studies. This view was confirmed by the International Commission on Zoological Nomenclature in Opinion 66 delivered in 1915 57.8.550 A History of Human Helminthology ova underwent indirect development 30. did confirm that the parasites could hav e profound pathological consequenc es. Roux95 and Dounon 25 concurred with Normand's view that A. he was in no doubt that the parasite s were the cause of this syndrome. stercoralis and A. Perroncito believed that the y played a part with hookworms in the genesis of anaemia in workers in the St. He expanded this view i n subsequent papers. while the parasites may exist in the intestine for long periods of time without ill effects. it became absolutely clear that infectio n with this parasite could have devastating consequences. while Askanazy suspected that the worm may produce a toxin 3. Thayer reviewed the question of the pathogenicity of the parasit e and summarized the position in the following way: The weight of evidence appears to be in favour of the view that. The means by which these effects are brought about. continued to be a matter of argument. ELUCIDATION OF THE MODE OF TRANSMISSION When Blanchard in 1890 reviewed the probable means by which infection occurred. however. They cause. Thira suggested that bacteria may enter the tissues through the portals in the mucosa left behind by the invading worms and thus exacerbate the illness 114.But in this connection the mother animals perform still another function. Thus. but also in the mucosa 107. as will be described shortly. however. other s disagreed. stercoralis. These eggs change into embryos which then emerge toward the intestinal lumen. This was confirmed by Askanazy in 1900 who demonstrated the presence of female worms in the epithelium of the uppe r small bowel and rhabditiform larvae in the mucosa associated with a chronic inflammatory infiltrate. intestinalis bores into the intestinal wall. as Grassi says. much epithelial destruction. 'innocent commensals of man'. that the most likely method of infection was by .85 Recent observations using transmission electron microscopy in infecte d animals suggest that Ophüls was correct.3 Askanazy was in no doubt that the worm was pathogenic. he remarked that the possibilities were not too difficult to conceive . in order to absorb food.. 113 The precise location of parasitic adult worms. Water had been incriminated. He presumed. With the discovery of autoinfection and overwh elming infection with S. but samples taken from the Mekong river in a heavily endemic area had been examined without finding any Strongyloides larvae. remain uncertain. and deposited their offspring in the midst of living tissue. for he conclude d from studies using special stains that the adult worms fed on the juices of the intestinal wall. Whereas Ask anazy3 and others 38. primarily into the mucosa and often into the epithelium of its glands. It would seem probably that this parasite alone may be the primary agent in many cases of chronic diarrhea.Strongyloidiasis 551 crypts. He also noted that eggs were often deposited in tunnels in the mucosa. In 1905. He summarized his findings: The A. they are by no means.. therefor e. Ophüls (1929) wrote: I have been unable to convince myself that either the mother worms or the rhabditiform embryos ever enter the stroma of the mucous membrane. Many earl y observers assumed that the effects were purely mechanical 40. A few years later. in that they deposit their eggs in the tissue of the mucous membrane.63 were of the opinion that the parasites frequently entered the stroma of the mucous membrane. however.. They were found to disappear from the cutaneous surface within half an hour. . he first found larvae in his stools and they were present in subsequen t examinations74. and that this was more likely when the skin was thin and the person was younger. present fragments of larvae down to the subcutaneous areolar tissue. In 1904. Looss succeeded in infecting himself by placing several hundred S. Looss demonstrated that the similar hookworm larvae could produce infections by penetrating the intact skin. to investigate whether a similar route of entry might not occur with Strongyloides. stercoralis larvae on the skin of his forearm. That this could indeed occur was shown experimentally when Wilms (1897) infected a human volunteer experimentally by the oral route. and concluded that larvae penetrated thin skin directly. One encounters them most often in the areas surrounding the hair follicle. van Durme was in fact almost certainly dealing wit h S. This stimulated Paul van Durme. Fülleborn then investigated th e penetration of human skin by these larvae and found that only a proportion of worms succeeded in penetrating the integument. Although he entitled his paper of 1901-1902 "Some observations on the larvae of Strongyloides intestinalis and their penetration through the skin". a Belgian working at the Liverpool School of Tropica l Medicine in England. Filariform larvae were applied to t he abdominal skin of guinea pigs. but effecte d entrance of thick skin via the hair follicles 60. Twenty hours after inoculation. at the level of the sebaceous glands. all the larvae have not disappeared. The fixed skin sections. although less numerous they can be seen at different levels in the dermis. seventeen days after swallowing infective larvae. after an hour. however. He wrote: After half an hour. rhabditiform larvae began to appear in the stools119. the larvae are found already deeply engaged in the dermis. More than twenty years after van Durme's studies. but remarked that he always found eggs in the faeces (which is a characteristic of that species). fuelleborni. Shortly afterwards. 64 days later. Kosug e examined the mechanism of skin penetration in experimental animals in more detail.26 Van Durme lamented that he was u nable to continue his investigations in order to determine whether worms introduced in this way passed to the intestine and produced patent infections. Fülleborn concluded that a larva only penetrated th e forearm skin when the epidermis was broken 35. thu s allowing the ingested larvae to develop into parasitic adult worms in th e bowel11. for he not only stated that the larvae were cultivated from a chimpanzee imported four months previously from Africa.552 A History of Human Helminthology consumption of vegetables which had been contaminated with worms. the n biopsies were taken at intervals. When he tried to infec t himself (then aged 59). Germany began to investigate the migratory route of S. another dog had . Fülleborn performed a tracheotomy on a dog then infected i t percutaneously. In a second experiment. In the light of all these observations. As already indicated. This idea was reinforced by Grassi in 1883 when he pointed out that immature specimens of S. stercoralis larvae in 1911. From his description. Grassi deduced that direct transformation of rhabditifor m larvae into parasitic adult worms must be taking place within the host without the interpolation of a sexually differentiated generation 46. a few rhabditiform larvae were found in the faece s beginning eight days after infection. When this observation was taken in conjunction with th e demonstration by Parona and himself that rhabditiform larvae could develo p directly into filariform larvae. the y continued to be passed until six days after infection. Looss had shown that afte r hookworm larvae had penetrated the skin. Grassi undoubtedly envisaged that moulting and maturation of worms from the rhabditiform larval stage through to adult worms took place in the gut. i. for he noted that although worms may persist in the gut for years without causing undue inconvenience. In his initia l experiment. the worms must have been rhabditiform larvae (which is most unusual). some of the larvae moulted and became female adult worms. and that the free-living adult forms were absent from the bowel. ascended the respiratory tree and passed to th e intestine where they completed their development (see chapter 20).e. Three days later. however. and van Durme had demonstrated that larvae had the capacity to penetrate the skin.83. despite interruption of the pulmonary oesophageal circuit. In this artificial situation which restricted worms to the trachea.Strongyloidiasis 553 DETERMINATION OF THE ROUTE OF MIGRATION AND TH E DISCOVERY OF AUTOINFECTION AND OVERWHELMIN G INFECTION Normand may have unwittingly app reciated the possibility of autoinfection. anything which tended t o diminish the patient's resistance often resulted in an exacerbation of symptoms to produce the clinical picture of Cochin-China diarrhoea 82. large numbers of larvae. the significance of the observation was not appreciated. Friedrich Fülleborn in Hamburg. appeared in the viscid tracheotomy mucus. In any event. the multiplication of worms within the body of the host without passing to the external environment. Wilms had shown that infection could be acquired by ingestion of infective larvae. but such concepts remained shadowy and vague until the routes of infection and migration of worms were established. Furthermore. Furthermore. A clue was provided in 1895 when Teissier claimed that he ha d found larvae in the peripheral blood of a patient with strongyloidiasis. possibly he was dealing with a different parasite 112. some of whic h appeared to be moulting. they passed to the lungs where they escaped into the airways. intestinalis were not infrequently found in the cadavers of patients who had remained in hospital for several months and in whom oral infections were most unlikely. Two days later. the animal was killed and female adult worms were found in the duodenum .. In 1911. In 1920. however.. whereas if filariform larvae obtained from tracheal mucus was injected. a severe intestinal infection developed.34 In this series of infections. Fülleborn so metimes found filariform larvae in the kidneys and liver. rhabditiform larvae originating from female worms were found in the tracheal mucus.larvae are eliminated after interruption of the tracheo-oesophageal tract but even so. Yos hida reported that after oral infection. These findings led him to suggest that the larvae migrated directly through the connective tissues 121.. larvae were found in the abdominal and p leural cavities within 24 hours. while the lung was free from infection. In another experiment in which free living filariform larvae were injected directly into the stomach of th e tracheotomized dogs. Between eight and twelve days after infection. larvae were discharged from th e upper oesophageal fistula and continued to do so for the next three days . further evidence began to accumulate gradually that was suggestive of the phenomenon of repeate d infection or autoinfection. In order to determine whether the slight infection that he had noted might result from larvae which passed through the lungs the n embolized to the small bowel in the systemic circulation..may pass from the lung veins and the left heart and reach the intestine by embolism via the intestinal arteries.554 A History of Human Helminthology its oesophagus excised and was also infected percutaneously. John Gage in the United States reported his observations on a 48 year old alcoholic patient who presented with an acute pneumonia.. stercoralis filariform larvae. Füllebor n tracheotomized a dog then injected larvae which had been obtained from th e tracheal mucus of another dog directly into the duodenal artery.. Concurrently with studies on the migration of larvae. A small number of parasites. As already mentioned. numerous larvae were recovered from the dog's saliva (the mouth was washed out with water).. Fülleborn summarized all these experiments thus: Chief results of the series of experiments on percutaneous infection: These proved that the normal route of infection of percutaneous penetrating. then on the following day. the resul ting infection was minimal. and that they appeared within the abdominal cavity and viscera within a similar period when placed on the abdominal skin.Strongyloides was from the lung to the intestine via trachea and esophagus. and supposed that they reached this site via the systemi c circulation. He rejected Grassi's . Fülleborn conclude d from these experiments that "the majority of Strongyloides. On examination of the sputum. Askanazy 3 then von Kurlow 63 found larvae in the deeper layers of the intestinal wall. Gage canvassed the ways in which autoinfection could occur. Six days later. larvae were found throughout the wall of the intestine and in the lungs 38. He concluded that in spite of only minimal morphological alter ations. the filariform larvae were altered biologically during their systemi c migration and became resistant to destruction by the gastric juices.. a slight infection occurs" 34.. Gage was surprised to find S. The pneumonia resolved but the patient's course continued downhill and he died two months later. This must be a slow process and extend over many years. for he saw the latter forms in the muscularis and i n lymphatics and veins of the submucosa of the bowel. spleen. rhabditiform or second-stage larvae could only do so if the mucosa was already ulcerated. he postulated both mode s of autoinfection (external and internal) that are generally accepted today: The finding of larvae in the sputum.. the presence of larvae in the lymph-spaces and lymph vessels of the intestinal wall suggests another plausible explanation . In this way a vicious circle is set up and the infection grows steadily worse. He found that rhabditiform larvae may transform into filariform larvae within the body. Thira. thence through the right heart to the lungs. He concluded tha t autoinfection was possible. develop into adult parasites. like Gage. Stekhoven described a case in whi ch the administration of purgatives resulted in the passage of hard faecal pellets which contained filariform larvae and suggested that this stage of the parasite could cause autoinfection 108. Further. kidney etc) and bloodstream were filariform.that the larvae pierce the intestinal walls. . liver. The factors which determine whether a rhabditif orm larva was excreted in the faeces or developed into a filariform larva within the gut were (and remain ) uncertain.Strongyloidiasis 555 hypothesis that direct transformation of rhabditiform larvae into filarifor m larvae then into adult worms may occur within the bowel as he failed to fin d evidence of intermediate stages of the parasite at autopsy. Yokogawa in 1913 reported that at autopsy he had found larva e (whether he was referring to r habditiform or filariform larvae is not made clear in the abstract of the Japanese paper) not only in the mucosa. and found that a small proportion of rhabditifor m larvae in the constipated stools had moulted.. examined the intestines of two humans and carried out experiments in cats and dogs. but also in the wall of the ileum. In 1919. in order to assess the role of constipation. found filariform larvae in the sputum of a man who wa s suffering from cancer of the kidney. and some probably did.after the patient had been in bed for two months. This view was supported by Shimura and Ogawa in 1920 who. I thought that the larvae were gaining entrance through the skin at this place. He then described the sam e phenomenon in an infected soldier who became constipated. when swallowed. infecte d successfully a dog by the rectal administration of filariform larvae obtaine d from a fresh stool 114. pass up the thoracic duct into the subclavian vein. all the larvae that he found in the variou s organs (lungs. appear in the sputum and. and who also had large numbers of rhabditiform larvae in his stools and vomitus 105. Nishigori .. lymphatic system and bloodstream of a patient 120. muscularis and serosa of the large intestine around an ulcer. enter the lymph stream. However.. With remarkabl e accuracy. Nishigori believed that whereas filariform larvae could penetrate the bowel mucos a easily. Similarly. also in Japan. Because of his personal filthiness and the irritation of the skin over his buttocks and back... and in order to support this concept. 38 Similarly. Nishigori (1928) reduced intestinal motility in infected dogs by the injection of opiates or th e administration of bismuth. chronic enteritis and chronic "bronchia l catarrh". Nevertheless. indicates that he was reinfecting himself. Fülleborn in 1926.the 'natural hatching oven' of the anal folds. with the former worms being smaller and having more cells in the genital primordium 79. (2) Actively piercing the intestinal wall.. they leave the intestinal wall in the flow of lymph... larvae followed one of three routes: (1) They enter the lymphatic. by way of the heart. Normand understood that the natural history o f strongyloidiasis was very variable.. they then enter the lymph nodes... they reach the lungs by way of the heart. became severely dysenteric an d . like Gage before him but probably unaware of that person's postulate.. others penetrate through the capsule of the liver. afterwards. whereas some patients at the other extreme went downhill progressively.. the filariform stage of Strongyloides larvae can be found after less than 24 hours. Ophüls in the following year described a 36 year old man who died of gastroenteritis and in whom post mortem examination revealed large numbers of filariform larvae in the mucosa and submucosa of the colon and in the mesenteric lymph nodes 85 then similar effects were described in patients with a dual infection with strongyloidiasis and leprosy in the Philippines 80 and in two patients in Brazil 116. after defecation. a number of persisten t carriers of infection complained of urticaria on the buttocks which Fülleborn thought was due to migrating filariform larvae: It is entirely possible that. As will be detailed later. This could not be confirmed by most investigators but Faust c laimed to be able to identify a dwarf filariform larva of direct type which he proposed to call "hyperinfective strain" as he considered that there was considerable evidence that this was the for m which was responsible for autoinfection 27.35 By these means of internal and external autoin fection..not only causes urticaria but also must be a cause for permanent new infection of the Strongyloides carrier. rhabditiform phases can develop into filariform larvae in the anal folds in residual fecal matter.. they reach the abdominal cavity. In confirmation of some of these speculations.vessels in the mucosa of the large intestine. they reach the lungs. from the surface of the pulmonary pleura.then.The penetration into the surrounding skin of filariform Strongyloides larvae. He postulated that in the process of autoinfection. In addition to reinfection within the intestinal tract (internal autoinfection).79 Nishigori also believed filariform larvae produced by direct and indirec t means could be distinguished morphologically. with many people being cure d spontaneously with elimination of all the paras ites.. entering the parenchyma.. suggested that autoinfection might also occur in another wa y (external autoinfection). Strongyloides infection may persist for many years. they invade the parenchyma (lung). (3) From the surface of the mucosa of the large intestine the invading larvae enter the blood capillaries. they pass through the portal system to the liver and the heart and so reach the lungs. afterwards.556 A History of Human Helminthology therefore injected rhabditiform larvae intravenously or into the abdomina l cavity of dogs and found that they had transformed into filariform larvae a s early as 24 hours later.. Some of them immediately penetrate through the diaphragm into the thoracic cavity.. through the thoracic duct.. particularly as I ascertained that at. Thus. even after the diarrhea has been arrested. that this relatively happy state of affairs is not always sustained. Why some patients shoul d eradicate the worms while others tolerate their presence has not yet bee n discovered.After some time. then a vast number of worms recovered 52.. Since that time. immunosuppressed. either after an intense infection or after a long period of alternating recovery and relapse.. with con sequent breakdown of resistance to the parasites.. it was realized gradually that there was a group of individuals who acquired a chronic illness with minimal o r moderate symptoms. even though the probability of such an outcom e may be small. however. The diarrhea sometimes ceases suddenly and. the disease evolves progressively into a terminal condition. It has become apparent that overwhelming infection. the prognosis of strongyloidiasis is uncertain. little by little. Sandground showed many years ago that dogs infected exper imentally acquired some resistance to reinfection but this finding does no t necessarily extrapolate to all humans 100. infection was still present in a group of Australian former prisoners-of-war between 34 and 3 7 years after removal from an endemic area 50.. At other times.. some patients appear to be unable to eliminate all the worms yet are able to contain the m within bounds and prevent their excessive multiplication. massiv e infection. he recovers a degree of vigor and weight. relapse easily. Certainly.Strongyloidiasis 557 died. It has been recognized increasingly over the last 25 years. Fülleborn in 1926 mentioned the instance of one of hi s patients who had been followed by him for 24 years and remarked that thi s probably represented the "welt-rekord" 35.Other patients. could supervene if patients becam e immunosuppressed for one reason or another (see next section). In the early part of the present centu ry. There may well be genetic variations in susceptibility to infection and the capacity to mount a completely effective immune reaction but these have not yet been defined.. in which there is a greatl y heightened multiplication of worms. the causal agent disappears quickly. Consequently. or disseminated strongyloidiasis.. more heavily infected. That these effects were not simply due to massive exposure to infective larvae in the environment wa s confirmed when dogs were infected experimentally with a defined number of worms. otherwise known as hyperinfection. This third group of patients develops enterocolitis... many patients have been reported with even longer durations of infection..recovery comes quickly. with all patients being at risk from severe disease. more than a year after infection... but he was in no doubt that this infection coul d cause a severe and at times fatal disease. RECOGNITION OF THE CLINICAL FEATURES Normand in 1876 reported that the symptoms associated with infection wit h this parasite were variable. He described four clinical categories: Some patients who are afflicted with diarrhea of Cochin China suffer a less intense infection.inflammation . the patient may recover.. "latent" in which laxatives had an unduly excessive effect. i n older persons. that the parasite was not a causative factor in th e production of diarrhoea 22. the patient is dead. 35 In 1958.558 A History of Human Helminthology develops analogous to that which accompanies a serious dysenteric infection. at other times the urticaria extends to the waistline in bands one or two fingers wide. intermittently. With rubbing and scratching of the skin the urticarial patches become so large that. Gage (1911) observed that a chronic but intermittent diarrhoea was present in 13 of his 15 patient s with strongyloidiasis 38. Darling (1911). experimental animal studies b y Thira114 and Sandground 99. "diarrhoea" which was intermittent. are indurated 'hard as a board' with urticaria. painless and unaccompanied by blood or mucus.74 Although this report has been cited as indicating Strongyloides infection38. ... having fought for a long time against the effects of diarrhea. The patient.areas the size of a hand. stercoralis infective larvae were applied to the skin of previously uninfected individuals. vertigo. a severe urticarial ras h developed which extended gradually along the skin over the next few hours and appeared to be due to larvae migratin g through the integument or subcutaneous tissues. and "neurasthenia" with anorexia. Enquiry revealed that eight out of ten of his patients who were chronic carriers experienced itching of the buttocks: an irritating pruritus accompanying the urticaria occurs. malaise and emaciation 5.. some larvae: are kept back in the tissues where they wander around under the skin producing the skin disease known as creeping eruption etc. Looss reported in 1905 that. and in a few hours. These included affection of the urogenita l tract presenting with haematuria 37 and of the lungs causing cough and wheeze 84. but when a person who had been a carrier for many years was infected likewise. at the buttocks.At other times the process is less rapid and may become entirely chronic. which was at times mil d with three or four soft. while on other occasions wa s associated with blood and mucus in the stools or was more choleraic (watery) in character.. develop an extreme marasmus and succumbs. Nevertheless.. pale motions a day. there was a transient itch. On the other hand. The other major symptom was a skin rash. Primary involvement of organs other than the gastrointestinal tract or ski n were described from time to time. 81 Thus. and continuing clinical observations confirmed that diarrhoea was a prominent feature of the infect ion. the eruption may well have been due to hookworms. concluded after a study of Strongyloides infection in humans and animals in the Canal Zone of Panama. at any time during the day but especially during the night in bed.. In 1926. the most important symptom was diarrhoea. They are able to live in the of form wandering larvae. Thus. like Grassi and others before him . Fülleborn notice d that when S. due to anemia."invasion " characterized by erythema and irritation of the skin at the site of entry of th e larvae. Arthur and Shelley introduced the term "larva currens" to reflect the rapid rate of migration compared with cutaneous larva migrans 2..about five years. Barlow in 1915 studied 23 infected persons i n Honduras and divided the clinical picture into four stages . nausea. Galliard reviewed reported cases of fatal strongyloidiasis and suggested that the patient had been debilitated in all cases of autoinfection so far recorded39. vomiting. given corticosteroids 20.118. stercoralis is a powerful opportunistic pathogen 101. Massive infections were recognized i n patients who were irradiated 94. If it had been said that all the patients reported with overwhelming infection had been debilitated. lymphoma1. then controlled the study by a comparison with uninfected men who had been prisoners in the same camps in Southeast Asia or in non-endemi c areas of Europe. In 1951. coproculture 53. and a modification of the Baermann technique 33.94 or protein-calorie malnutrition . He also indicated that this technique was useful for assessment of the parasitological responses to treatment in patients in whom diarrhoe a persisted after therapy: "The microscope revealed immediately whether it was a matter of persistent infection or the effect of parasitism" 81. and concluded tha t S. lower abdomina l pain. pruritus ani and weight loss were significantly more common in infected individuals 50. and tha t gastrointestinal symptoms including diarrhoea. weight loss and weakness 56. described the frequen t concomitant bacterial infections. respectively. many observers over the years have recognized that examination of simple faecal smears often fails to provide the diagnosis and a number of attempts have been made to improve diagnostic sensitivity by th e development of concentration techniques. He found that two thir ds of patients complained of intermittent urticaria. Grove solved this problem by analysing the symptomatology of 44 men with chronic strongyloidiasis (35 years) wh o had long since left the endemic area and were no longer infected with othe r parasites. DEVELOPMENT OF DIAGNOSTIC METHODS Normand described a potent means of diag nosing strongyloidiasis when he first discovered the worms. emphasized that immunosuppression is usually present. Deschiens and Taillandier showed that the diagnosis could also be made by finding parasites in duodenal fluid r emoved via a duodenal tube 24. Nevertheless. with 30% having the pathognomonic larva currens. then this was echoed by Hartz55 . Scowden and his colleagues reviewed this syndrome. One of the major difficulties which has confronted attempts to define th e symptomatology of strongyloidiasis is frequent concurrent infection with other gastrointestinal pathogens. particularly septicaemia and meningitis . Those which have been usefull y employed in strongyloidiasis include the zinc sulphate concentratio n technique31. In 1925. In 1978. or who were suffering 55. This . then this was followed by diarrhoea. indigestion. headache .Strongyloidiasis 559 larvae were found in the urine and sputum. then this would have been closer to the truth. for he found them during a microscopical examination of the faeces. Hinman in 1939 in an uncontrolled analysis of 85 patients reported that abdominal pain was the most frequent presenting complaint. anorexia.93 from leprosy80. In 1970. de Langen in 1928 realized that the condition which he had previously reported a s "idiopathic hypereosinophilia" was in fact due to S. . it is now realized t hat most patients with chronic strongyloidiasis either have no eosinophilia or.84 . vomitus105. new agents introduced for the treatment of hookworm such as oil of chenopodium. many patients failed to respond to such therapy and he wrote that he was currently experimenting with santonin. He believed this often suppressed mucus production and caused disappearance of parasites (this was undoubtedly coincidental) . sputum38. asserted that no known anthelmintic was of any value 46. These immunodiagnost ic techniques.560 A History of Human Helminthology was claimed to be a much more effective tool for diagnosis by some authors 87. Similarly. and then proposed to try essential oils. sulphurs. but Seifert did not agree and believed that thymol was better 102. duodenal fluid may now also be obtained at upper gastrointestinal endoscopy and may reveal parasites 50. THE SEARCH FOR EFFECTIVE TREATMENT The first therapeutic regimen which Normand tried was to put his patients on a "rational diet" of milk. Nevertheless. Beal and his colleagues described a simplifie d method for obtaining duodenal fluid by means of a string coiled in a gelatin e capsule9. however. however. quinine and mineral waters i n "rebellious" cases81. Indeed. In many modern centres. mercury and arsenic. was probably that of Daland who in 1908 reported a patient who had a blood eosinophil level of 38% 21. carbon tetrachloride an d tetrachlorethylene were found to be ineffective in strongyloidiasis. Grassi. this view turned out to be quite correct. Nevertheless. stercoralis 13. Perroncito 90 and others after him considered that ethe real extract of male fern was valuable. a mild increase in blood eosinophi l levels50. betanaphthol. The diagnosis has also been made from time to time by recovering larva e from other body fluids and secretions. The incidental finding of an eosinophilia on routine examination of blood smear s has not infrequently stimulated a search for S. but not by others19. Deschiens and Taillandier describe d thickening of the duodenal wall on barium meal examination of the uppe r gastrointestinal tract 24. cerebrospinal fluid 78 and ascitic fluid 4. stercoralis infection64. In the following year. The first recorded case of eosinophilia in strongyloidiasis.65. at most. Gage in 1911 recounted a case of Dr AC Eustis who in 1907 had shown that the patient had strongyloidiasis and an eos inophilia of 56% 38. Attempts have been made to develop immunoassays of strongyloidiasis a s experience has shown that infection is often hard to diagnose parasitologically in chronic cases. include skin testing with Strongyloides antigen36 and the demonstration of antibodies in the serum 12. These include urine 37. he reported that large quantitites of olive oil were useful because o f its mechanical action 82. Radiological studies may suggest the diagnosis and provide an indication of the severity of intestinal damage. Kudiche showed that some dye-stuffs such as crystal violet an d fuchsin killed filariform larvae in vitro 62. and stated that examination of autopsied animals revealed that parasitic female worms were killed in situ although the viability of already hatched larvae was unaffected28. another benz imidazole compound. may be active i n strongyloidiasis 51. . Two hundred human cases were then treated with oral gentia n violet and 45 of the 47 patients followed up we re said to be cured 29. ratti and S. however. Several fatal reactions to the drug occurred . stercoralis have indicated that ivermectin. Subsequent observations. Three years later. which had a broad spectrum of anthelmintic activity 16. Faust also showed that crystal violet and gentian violet were active in vitro. Vilela and colleagues re ported that this agent cured 100% of 38 patients117 but subsequent investigators did not find such uniformly high rates. Brown and his collaborators described a new benzimidazole drug. with ap parent success 77 and this may turn out to be more effective than thiabendazole.Strongyloidiasis 561 In 1925. there was no support for the belief tha t "compound solution of iodine" was effec tive as had been held by some 106. Martirani and Rodrigues (1976) used cambendazole. he advised that patients whom he had thought were cured had relapsed 65. Unlike previous anthelmintics. thus permitting a relapse of the illness. however. Finally. In the following year. In 1957. reduced the eosinophilia and expelled the worms64. recent studies of mice infected with S. have supported de Langen's view and failed to confirm the efficacy of the drug 104. attention has turned to finding a drug which will eradicate all th e worms. Subsequently. or for the claims that bismuth and tin were efficacious 23. Similarly. MacCowen and his colleagues demonstrated the anthelminti c properties of a dye in the dicarbocyanine series called diathiazanine iodide 76. however. In 1961. He declared that oral administration of gentia n violet caused all infections to undergo the direct mode of larval development. Because a few resistant worms may multiply. then experimented in monkey s and claimed striking results. In the following year. a member of the recently discovered avermectin family of anthelmintics. this drug was shown to be active agains t S. and the drug was withdrawn from the market. thiabendazole. stercoralis by Swartzwelder and co-workers who claimed cure to 89% of 18 109 patients111. de Langen reported that gentian violet given orally in conjunction with intravenous injection o f tartar emetic relieved the sympto ms. 562 A History of Human Helminthology UNDERSTANDING THE EPIDEMIOLOGY AND THE EVOLUTION OF EFFECTIVE PREVENTIVE AND CONTROL MEASURES Perroncito (1880) was perhaps the first person to point out an associatio n between infection with S. In parts of Papua New Guinea. but these are unavailable in many endemic areas. Brown and Girardeau in Zaire reported in 1977 that they ha d found that 34% of 76 children under the age of six months were infected. a rash appeared at the site of infection and was followed by lymphangitis. abdominal pain and bouts of diarrhoe a appeared after three weeks. the factors determining the prevalence of strongyloidiasis are very similar to those already described for hookworm infection. Infections in humans were first reported by Blackie in Southern Rhodesia (Zimbabwe ) in 1932 10. then Pampiglione and Ricciardi demonstrated ova 28 days after experimental human infection 86. and no attempt s have been made to control it in isolation. The most effective control measures have been the installation and usage of safe waste disposal systems. malaise. A cough was noted on the fifth day. the diagnosis is made by finding the characteristic egg s instead of larvae in the faeces. The toxicity and ineffectiveness o f most anthelmintics has militated against mass treatment programmes. respiratory distress and generalized oedema 59. OTHER SPECIES OF STRONGYLOIDES S. Similar observations have been made by many investigators since that time. fuelleborni-like worm which affects infants causing abdominal distension . . Con sequently. then anorexia. In this instance. infection has been described with a S.89. and they recovered three larvae from the breast milk of a nursing mother 15. Tomita reported in 1941 that he found eggs in the stools between 16 days and 11 months after experimental percutaneou s infection of a human 115. In contrast to infection with S. FUELLEBORNI This organism is a common parasite of old world monkeys and apes. It wa s described by von Linstow in 1905 73. Strongyloidiasis is but one of a number of soil-transmitted helminth infections. stercoralis. 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St eroid therapy and strongyloidiasis. (Studien über Strongyloides stercoralis . A new course for migrating Ancylostoma and Strongyloides larvae after oral infection. O emprego do tiabendazol no tratamento da estrongiloidiase de outra s parasitosis humanas. Journal of Experimental Medicine 6: 75-105. Travassos. Saigon (1913). THIRA T.) Mittheilung der medicinische n Gesellschaft zu Tokio 33: (11) 2-3. Anchylostoma duodenale und Anguillula intestinalis . Rio de Janeiro. 1897 120. Lancet i: 1396-1398.568 A History of Human Helminthology 120: 171-172. On the pathogenesis of Strongyloides stercoralis . 1895. TOMITA S. fülleborni. 1942 116. with German summary 115. NWOKOLO C. WILLIS AJ. (On local reaction of infected skin. de AZAVEDO AP. pp 475-488. Journal of Parasitology 7: 46-48. Far Eastern Association of Tropical Medicine: Comptes Rendus Troisième Congrès Biennal. Hospital. ZACATO M. L. 1938. CAPELL JI. 1920 . Lesoes produzidas no honem por Strongyloides. 1939 117. Abstracted in Tropical Diseases Bulletin 39: 100. VILELA M de P. RODRIGUES LD. On the occurrence of Strongyloides intestinalis in the United States. TORRES CM. MARTIRANI I . and proposed the parasite as a cause of Cochin-China diarrhoea 1876 Bavay described the development of free-living adult worms from faecal larvae and the subsequent appearance of larvae (rhabditiform) [He observed the indirect cycle of development] 1876 Normand. They believed that the larvae were the offspring of the worm found by Normand in the intestines of a patient [Although they did not realize it. filariform) in faeces which had been kept for several days. this was at first considered to be a distinct species and was named A. discovered parasitic adult worms in the intestine. which were then named Anguillula stercoralis by Bavay. Gothard tunnel 1881 Perroncito cultivated free-living adults from rhabditiform larvae. then observed the laying of eggs and the hatching of rhabditiform larvae which developed into filariform larvae (the indirect cycle) 1882 Grassi postulated that the parasitic adult worms were parthenogenetic 1883 Looss observed both direct and indirect development in vitro simultaneously in the same preparations but did not report the fact 1883 Leuckart concluded that A. fuelleborni) filariform larvae through the skin of guinea pigs 1904 Looss produced a patent infection in himself after placing larvae on the skin of his forearm 1905 S. and observed their further development in vitro into filariform larvae but not into free-living adults (the direct cycle) 1880 The parasite was found to infect miners working in the St.1. stercoralis larvae. intestinalis 1877 Normand and Bavay found larvae (in retrospect. in faeces of French troops returned from Indochina. stercoralis were the same parasite and that there was an alternation between the parasitic and free-living generations 1883 Grassi suggested that autoinfection with direct transformation of rhabditiform to filariform larvae may take place in the gut 1884 Golgi and Monti reported that rhabditiform larvae could undergo either direct or indirect development 1891 Sonsino described the presence of parasites in the mucosa of the small intestine 1897 Wilms produced a patent infection in a human volunteer 17 days after ingestion of filariform larvae 1901-2 van Durme described the penetration of Strongyloides (probably S. at autopsy. 1876 . intestinalis and A. rhabditiform). they had observed the direct development of rhabditiform into filariform larvae] 1878 Grassi and Parona showed that the larvae produced by A. fuelleborni was described as a parasite of monkeys and apes 1911 Fülleborn showed using dogs with a tracheotomy or oesophagostomy that the majority of migrating filariform larvae followed the tracheo-oesophageal route described for hookworm by Looss 1911 Gage found filariform larvae in the sputum of a human 1919 Thira produced patent infections by rectal administration of filariform larvae.Strongyloidiasis 569 Table 21. Landmarks in strongyloidiasis ___________________________________________________________________ Normand discovered larvae (in retrospect. intestinalis in the gut were identical with A. described the frequent occurrence of urticaria in infected patients.570 A History of Human Helminthology thus supporting the possibility of internal autoinfection Larvae were found in duodenal fluid obtained with a duodenal tube Fülleborn suggested that external autoinfection may occur when rhabditiform larvae develop into filariform larvae in the perianal folds. fuelleborni was described by Blackie as a parasite of humans 1945+ Disseminated infections in immunosuppressed persons became increasingly recognized 1957 Dithiazinine iodide was reported to be an effective treatment by MacCowen and colleagues but was subsequently withdrawn following fatal reactions 1962 Thiabendazole was reported to cure patients with strongyloidiasis by Vitela and coworkers 1976 Martirani and Rodrigues reported that cambendazole cured patients with strongyloidiasis but the drug was subsequently withdrawn ___________________________________________________________________ 1925 1926 . and described a skin test for the diagnosis of strongyloidiasis 1932 Kreis and Faust claimed (erroneously) to have found male adult parasitic worms 1932 S. Bianchi complained of loss of appetite. His urine tasted sweet suggesting the presence of sugar and contained large quantities of protein. the liver was enlarged and fatty. his condition deteriorated. a nutritious diet. was admitted to St. When the body was dissected three days after death. Despite supportive treatment with various tonics and sedatives. lecturer in materia medica. a middle-aged Italian barometer-maker. Bartholomew's Hospital in London. an immense number of minute. The adult worms.They penetrate intracellularly. myositis in persons with heavy infections Diagnosis: demonstration of larvae in muscle biopsy. invade the gut epithelium and moult four times. they excyst in the upper small intestine. tuberculous cavities were found in the upper lobe of each lung. Paolo Bianchi. on a number of occasions previously. Thomas Wormald. Such a condition had come to the attention of the demonstrator of anatomy. diarrhoea. produce newborn larvae which enter the bloodstream and seed the muscles. the kidneys showed features of chronic nephritis.Chapter 22 Trichinella spiralis and TRICHINOSIS SYNOPSIS Common name: fleshworm Major synonym: Trichina spiralis Distribution: worldwide except Oceania Life Cycle: When infective larvae in cysts in meat are ingested by a carnivore. diarrhoeic stools. cough and back pain and was found on examination to be emaciated and weak and to have an enlarged liver and lower limbs swollen with fluid. His abdomen became distended and painful and he died on 29 January 1835 following the passage of bloody. serology Treatment: supportive DISCOVERY OF THE LARVA IN HUMANS In December 1834. and the small intestine was ulcerated92. England under the care of Dr George Roupell. sometimes as a result of the 571 . At post-mortem examination. whitish specks were observed scattered throughout the muscles. become surrounded by a cyst wall. 1-2 mm long. and become infective within three weeks Hosts: most mammals Major clinical features: fever. and the application of leeches. for despite his youth. he found that a small worm was coiled up within nearly every cyst.' Mr. surgery. Paget's presentation met with sufficient approbation that he was . even to the present day. the salient features being recorded in the Minute Book of the Society101. Paget. do you know anything about intestinal worms?' and answer was. Paget was invited to communicate his findings to the Abernethian Society which was the medical students' society at St. had done83. thus suggesting that another dissector may have first noticed the abnormality. he said 'Brown. with which I soon observed structures within the worm which were before invisible. for he examined the specks with a lens and found that they were cysts. is that Paget did not rest content with the explanation of bony spiculae. Brown at once lent me his simple dissecting microscope. so he took Paget to the celebrated botanist. There is no doubt as to his intellectual ability for he won the prizes in medicine. he sought a microscope with which to them examine them more closely. In the dissecting room at the time was James Paget. Owen thought so. He dexterously pulled a worm from a cyst. so he repaired to the only scientist he knew in London. both teachers and fellow-students.nothing whatever. On the other hand.. It is uncertain whether Paget himself was the first to observe the specks in this patient. an intelligent student. Children entered his room. no such instrument was to be found in the hospital at that time. Robert Brown. This he did on 6 February 1835 with Dr.. and at times. These specks had been regarded as bone spicules in the muscles. A number of factors must have contributed to the successful outcome of Paget's tenacious search. that the muscles presented an uncommon appearance" 76 and also: "Mr. What is clear. Arthur Farre in the chair. principal keeper of the natural history collection at the British Museum. Finally. Paget himself recalling the events 31 years later wrote: "The report soon ran through the dissecting room that there was another body with spiculae of bone in the muscles"80. Moreover.first observed the worms in the Italian"74. Children. As the discoverer of the entozoon. Being desirous of investigating these creatures further. Paget himself has recounted what then happened: I remember that when Mr. thank heaven . controversy. Children had no microscope either. and I believe I still possess my sketch of it. he was wellacquainted with the biological world. a 21 year old first year medical student.80 Thus began a saga which has remained a subject of interest. acrimonious debate. one Mr. or else wished to see them in more detail for himself. Certainly. Paget. Paget himself attributed his success to the fact that he "looked-at" and "observed" the specks rather than merely "saw" them as others.. 'No. Bartholomew's Hospital. He was clearly of an energetic nature and enquiring mind. however. he had already published together with his brother Charles a book on the natural history of Yarmouth. for he wrote in his paper printed later that year: "it was observed by Mr. Unfortunately. almost immediately afterwards. or else were thought to be caused by deposition of earthy matter.572 A History of Human Helminthology gritty nature of the specks leading to rapid blunting of the scalpels. chemistry and botany in 1835. together with an introductory note. On the evening of 24 February 1835. it was left to Richard Owen. Paget described the appearances of elliptical cysts with pointed ends 1/40 of an inch in length and the entrapped. Instead. it was written twice in the first person76. and gave it the specific designation "spiralis" to indicate its spiral form. described by Zeder110 . Such a report headed "Description of a peculiar animalcule observed in human muscle"81. Given that this happened. from the Greek (THRIX) [combining form . to the Gazette's editor. Although the disease might therefore more correctly be called "trichinellosis". "trichinosis" is entrenched in the literature and is hallowed by tradition. The terms "trichinosis" or. Capsularia. Bartholomew's Hospital. The best that can be said for Owen is that he obscured the truth by a masterpiece of dissembling. to publicize the discovery. however. name the worm. it is almost incredible to find that it was Owen who provided the definitive report. But the paper was never sent and it was to remain unpublished for nearly 150 years until it was printed in 197882 and again in 197981. In 1896. It was at that point in 1835 that the story began to go awry. lecturer in anatomy and physiology at St. it was merely said . Owen presented a paper entitled "Description of a microscopic entozoon infesting the muscles of the human body"75 to the Zoological Society of London and demonstrated the parasite with the aid of a microscope belonging to Mr Prichard. with the comment being made that Wormald had previously seen them a number of times (thus implying that Paget's finding was not out of the ordinary) and Farr being praised as one "who has paid much attention to the subject"75. spirally-coiled worms 1/25 of an inch long. to submit a manuscript describing the discovery to the London Medical Gazette. This presentation was published with minor variations not fewer than four times in the ensuing year.75.82 was duly written. Trichina. He noted that the parasites were rounded bluntly at both ends but tapered towards the end that appeared to be the head. dated 10 February 1835.Trichinosis 573 encouraged by Edward Stanley. 30 years of age and lecturer in comparative anatomy at St. Paget's name was sandwiched between those of Wormald and Farr. one then turns to Owen's text for due and explicit acknowledgement of Paget's role.77 and twice ostensibly as third person reports but undoubtedly written by Owen74. Concerning Paget. Paget considered that the genus to which the entozoon most closely approached was that of the roundworm. "trichiniasis" were therefore used to denote the disease caused by the organism. created a new genus. In one version published in April 183574.(TRICH-)] meaning "hair". Since Paget had not only discovered the worm but had prepared an account for publication. occasionally. but finally admitted it to the Class Entozoa of Rudolphi. Railliet86 altered the generic name to Trichinella since the name Trichina had been employed for a genus of the Diptera (flies) in 1830.75 Owen had some trouble classifying the parasite. and become immortalized in print. and believed that they possessed an intestinal canal. Bartholomew's Hospital. Paget wrote: "The admirable memoir of Professor Owen (was) much more complete and exact in zoological detail than anything I could have written"80.. infesting in myriads the human muscle. during life. among many reasons. giving preference to papers by members. of course. John Bennett at the British Museum.I shall be mentioned as the first observer of their existence. This question has recently been discussed intensively by Campbell26 who has also published two letters written by Paget soon after the discovery.?) said that it would in the end be best not to stand too far forward...574 that: A History of Human Helminthology (the specks) having been again remarked. Paget is patronized as an "intelligent student"76 and this time a footnote. though this was not to be had without some trouble.comes so near the marvellous that it required some good name to authenticate it to prevent its being. despite his explicit denial. and Mr.and the account is to be published either in the Transactions of the Zoological or the Medico-Chirurgical Society.. Brown and Mr. Paget with the assistance of Mr. Campbell26 has distilled four likely reasons for Paget's actions.75 In the account printed in the following December.82 From all of this. or the Society at which the description might have been read. I do not yet know whether I shall write the description myself.... (wh..as well as to their peculiar structures..82 In a subsequent letter two weeks later.I am very well contented that in the papers which will probably be published. Paget said: You will be interested in learning that I have lately discovered a perfectly new animalcule. self interest... but I fear not modesty. Besides the subject. I have taken care that I should receive at least some credit for the discovery.81.. the antithesis of clarity.. Why should Paget have given way to Owen like this? Many years later (1866).. In writing on 11 February 1835 to his brother Charles.by Mr. When Paget's and Owen's texts are both examined.I should rather think the latter.. This suggestion that Paget was incapable of writing an expert zoological description does not stand up to critical analysis. It is a subject with which I was PREVIOUSLY entirely unacquainted. is that Owen claimed for himself the priority of independent discovery of the parasite... has been able to make out their organization more clearly.. First. Paget did not make the two blunders that Owen did when he called the tail of the worm its head and denied the existence of an alimentary tract in the parasite.76 The clear implication of this. Indeed. a student of the hospital. Owen was furnished with portions of the muscle and made the following observations. modesty seems a strong factor for he was but .utterly disbelieved. our lecturer on comparative anatomy will do it . and I might very easily have fallen into error as to the affinity of species .. would not have printed it in their earliest transactions. or whether Mr.I should probably have been obliged to send it to some (minor?) periodical. is added: The existence of the entozoon was at the same time satisfactorily determined by Mr. he added: I think I have done rightly in not publishing this account for the folln.. Paget. You may add perhaps. the former compares quite favourably with the latter. who suspected it to be produced by minute Entozoa.. Whichever be the case. The suspicion was found to be correct.81. as he having used far more powerful microscopes than I had. Owen. as Paget later indicated "disliked me . It was not until the epidemics of trichinosis in Germany in the 1860's brought the worm and the affliction that it caused to general attention that interest in the . but the two of them struck a deal. the waters were muddied even further. the chemical examination conducted by Gmelin yielded 73 parts phosphate of lime. They lay in the cellular tissues between the fibre-bundles. it is possible that Paget may have been embarrassed and frustrated by having no suitable illustrations of the parasite whereas he could have expected Owen and his illustators to produce masterful and detailed drawings. it is now clear that whether or not they were trichinellae is irrelevant since they were certainly not recognized as such by Tiedemann. and roundish. To this may be added political expediency. Tiedemann found white stony concretions in most muscles. spiralis.Trichinosis 575 a first year medical student embarking on a career in an intensely hierarchical profession. but this accord was gained only with "some trouble" on Paget's part. and as has been seen. In any event.98 Claims that Tiedemann's concretions were trichinellae were dismissed by Leuckart on the grounds that they were too big and the work was mostly concerned with chemical analysis of their nature67. resembling albumen or fibrin. London55. Not only did he have his own reasons for yielding to Owen. In a similar vein. this finding had never been published 107. however. This passage has been translated by Cobbold: At the post-mortem examination of a man who had been a great brandy drinker and who died from thoracic dropsy after several severe attacks of gout. Owen and Paget had done this themselves. especially at the extremities. and became the chief opponent of my progress" 83. Owen agreed to give Paget credit in his presentation. his lack of access to a powerful microscope made him diffident about describing the structure of the worm in detail. being from two to four lines long. for they both referred to the patient recorded in 1833 by John Hilton. During this period. most writers on this subject generally referred to Owen as the discover or Trichina spiralis. a number of German writers led by Henle52 in turn insisted that these bodies were first seen by F Tiedemann and published in Froriep's Notizen in 1822. Paget was in a position of ethical superiority but political and technical weakness. The definitive discovery of the parasite caused various commentators to attempt to diagnose in retrospect some of the reports in the earlier literature. and 20 parts of animal matter. . Finally. also contained cysts of this worm. It is little wonder then. that for the next three decades. It now seemed probable that they were in fact T. Thus. it became apparent that a specimen of sternomastoid muscles deposited in Guy's Hospital museum in 1828 by its then curator. demonstrator in anatomy at Guy's Hospital. Hilton had described cysts in the muscles of a cadaver but had thought that they were probably cysticerci. 7 parts carbonate of lime. for he was a student of Wormald who. was carried out in the most niggardly and obscurantist fashion by Owen. frequently also attached to (or near) the walls of the arteries. Mr H Peacock. Furthermore. Thirdly. Owen thought it was a single layer of host origin. But first it was critical that the initial observations be validated by finding the same parasite in other people.. saying: the cyst is adventitious. and. although he was to comment sixteen years later. as I know you are a keen hand for parasitical things. When a writer in the Pall Mall Gazette in England indicated that the history of Trichinella "was not yet clearly made out".35 and Owen79..unequivocally establish Mr Paget's priority in this relation. It may be that senility impaired his judgement or his memory when he took up the cudgels again in the correspondence columns of The Lancet in November 1882. The letters. a second patient was found to be infected just two weeks after the initial discovery74 and yet a third patient from that hospital was described later that year by Farre41. B. This was not long in coming from a number of quarters. but the apparent spontaneity of the missive does not square with Owen's own account in 1835 when Owen declared that he had sought the material from Wormald. Uncertainty surrounded the nature of the cyst enclosing the spiral worm.576 A History of Human Helminthology question of its discovery was rekindled. for he quoted the note from Wormald which accompanied the specimen of muscle: Dear Owen. foreign to the entozoon and composed of the cellular substances of the body infested. On the . morbidly altered by the irritation of the worm"76. Cases were then reported by Harrison in Ireland. Cobbold summed it up by writing in The Lancet: In the interests of truth. Knox in Edinburgh and by various observers in continental Europe and in North America.109 Not only does this note imply that it was already known that the specks were of an animal nature. Spencer Cobbold thought it his duty to write to The Times to put forth the facts. and once more claimed to be the discoverer of the T.. his own communication did little to advance his cause. with the latter's incomprehensible circumlocution doing nothing to change Cobbold's conviction that Paget had discovered the parasite. Owen remained uncharacteristically silent publicly during this period. In St. as I believe.. These included the nature of the organism and its cyst and its significance for the host. which occupies the muscle of a subject under dissection at St. This last letter of Owen's stimulated another exchange between Cobbold34. H.I send you some sort of organised being. spiralis 78. . Indeed. Bartholomew's Hospital itself. from 'crabs' downwards. I send the enclosed for your inspection. Paget's discovery and Owen's promulgation of awareness of the parasite raised many important questions. This included a letter from Paget himself making plain his view of the facts80 and a communication from "Two former presidents of the Abernethian Society"101 who quoted an extract from the Society's minute book of 6 February 1835 which described Paget's talk. This led to a spirited exchange in the columns of both that paper and The Lancet.32 Perhaps not surprisingly. I rejoice that our knowledge of the circumstances connected with the discovery of the fleshworm is now complete. its precise nature was obscure to the early observers for they had little concept of helminth life cycles. he was correct in denying the presence of mature reproductive organs. those workers were of the view that trichinellae were probably the offspring of a roundworm that was already known in its adult state by another name. The stage was about to be set for elucidation of the life cycle of the parasite. he thought it possible that the worms reproduced by a process of gemmation or budding74. IN ANIMALS In 1846. Felix Dujardin . an outer coat of fine fibres laid down by the host. was of the view that it had two components. When he examined a portion of the flesh under the microscope. and an inner homogeneous layer derived from the parasite70. but the most telling points had been made several years earlier by the German. Joseph Leidy. in particular. spiralis observed in human muscle and duly communicated his findings to a meeting of the Academy of Natural Sciences in Philadelphia.Trichinosis 577 other hand. they had all been killed by cooking62. Moreover. However. the roundworms. while Hubert Luschka. It is only in recent times that it has been shown with the aid of the electron microscope that the cyst is formed by multiple infoldings of the sarcolemmal sheath of the muscle fibre38. (West) Germany22. (in present-day West) Germany. a prominent anatomist in Heidelberg. an error which was perpetuated by Theodor Bischoff. and the Frenchman. it was not at first realized that the parasite living in muscles was a larva and not an adult worm. Leidy could detect no difference between this parasite and the T. each containing a coiled worm. 40 Carl von Siebold95. who both stated unequivocally that the encysted trichinella was a juvenile form. Bristowe and Rainey considered that the cyst was a product of the worm itself. he found that it was teeming with chalky cysts. A brief abstract was prepared by . professor of anatomy at Tübingen. a number of investigators including Vogel. In particular. fortunately for him. Even though Owen was inaccurate in many aspects of his description of the worm. Farre identified certain structures as gonads and mistakenly thought that the encysted worms were sexually mature animals. a 23 year old American doctor was at home eating a slice of pork when he noticed some minute specks in the meat which reminded him of the trichinous spots that he had seen in the muscles of a human cadaver only a few days previously. Some of these erroneous observations were corrected by Luschka who demonstrated that what Owen had called the head was in reality the tail. Farre in the same year described a complete digestive tract which convinced him that the worm was not one of the "simple parenchymatous forms" but approximated the "more highly organised species of entozoa"41. but first it was necessary to have a system in which these events could be investigated experimentally. Although Owen had described the parasite correctly as a worm. Herbst had kept this badger in captivity for one and a half years and had fed it partly on vegetables and partly on the remains of animals that he used in his work. Three and a half months . In fact. Diesing in his Systema Helminthum in 1851 classified the worm found by Leidy as T. On examination four weeks later. When the badger died in November 1850.45. which corresponded exactly with those described by Owen. cats and dogs opened the way for exploration of these ideas and it was Herbst who had the initiative and perseverance to follow it through. Herbst then extended these observations in 1848 by finding similar worms in the muscles of a dog. One animal was sent to the country and left free to roam while the other two were retained. Guret (1849) had recorded his discovery of trichinellae in a cat48. Despite its annotation in a British journal and in a German publication. a wide range of mammals was found to be infected in nature. he fed the flesh to three dogs that were six weeks old. The second experiment followed his discovery of trichinellae in a badger. Nevertheless. but the encapsulated worms were dead. Herbst found a considerable number of trichinellae in its muscles. and others were shown in the laboratory to be susceptible to infection with this organism33. This idea followed naturally from the recent publication by Steenstrup of his theory of the alternation of generations (see chapter 2). In August 1845. he suggested that they were an intermediate stage awaiting transfer to another host95. in the current state of civilisation. the eating of human flesh was not a common occurrence. This time. spiralis was peculiar to humans.578 A History of Human Helminthology the secretary of the society and was published in its minutes61. Neither of these discoveries were reported until 185153 by which time. the implications of this observation for an understanding of the epidemiology of trichinosis were not realized. affinis 39 on the assumption that T. he first attempted to transmit the infection directly by inserting 30 cysts containing live larvae between the skin and muscles of another cat. and transmission of the parasite this way must have been rare indeed. in the voluntary muscles of an old cat. Ernst Herbst had found large numbers of trichinellae. the cysts had attached to the connective tissues and the muscles. Trichinellae had in fact been observed in a non-human host a year earlier than Leidy had seen it. von Siebold could see difficulties with this postulate. ELUCIDATION OF THE MODE OF TRANSMISSION: DISCOVERY OF THE ADULT WORMS EXPERIMENTAL TRANSMISSION OF INFECTION When von Siebold declared in 1844 that trichinellae in human muscle were larvae.37. Subsequently. The discovery of trichinellae in pigs. When Herbst found trichinellae in a cat in 1845. he suggested that ingestion of Trichuris eggs by humans might result in liberation of larvae which then bored through the intestinal wall and migrated to the muscles where they encysted as T. These findings were greeted with considerable scepticism. cats . Küchenmeister. dispar by consumption of pork beset with trichinellae. spiralis cysts to rabbits. but also because Herbst's descriptions of the worm were inaccurate and it was believed that he may have confounded some other species of roundworm with trichinellae. By the same token. spiralis and other nematodes found commonly in humans.were to play leading roles in the next phase of discovery. who had recently shown that cystic worms. spiralis 58. eggs were liberated in the gut and passed via the bloodstream to the muscles: "there can be no doubt that their growth in the aforementioned three dogs had resulted from the intake of badger meat"53. Küchenmeister believed it likely that the trichinellae found in the pig were identical with T. Rudolf Leuckart took up the question and fed T. To Virchow must go the credit for first finding the adult worms in the intestines. Alternatively. spiralis was an immature form of the intestinal whipworm. He came to the conclusion that T. particularly as Virchow106 and Zenker112 felt compelled to defend their positions against Leuckart who was constantly appearing in print with incomplete notices. were in reality immature stages of tapeworms. previously thought to be distinct species. DISCOVERY OF THE ADULT WORM Three figures . while Zenker hammered into place the final link in the chain of events by explaining how human infections were acquired. thought that humans might possibly become infected with T. Heller has remarked that it is not easy to determine the merits of each one from his publications. with a modicum of misguided foresight. Trichocephalus dispar (now known as Trichuris trichiura). A number of years were to pass before similar experiments were repeated and Herbst's observations were confirmed and extended. principally because the trichinellae of animals were regarded as being distinct from those found in humans. carefully examined the anatomy of T. in some as yet undetermined fashion. The third dog was examined one year after eating infected badger meat and multiple trichinellae were found in a biopsy of one of its muscles. Virchow and Zenker .Trichinosis 579 later. The account which follows generally approximates the conclusions that Heller made after a careful examination of the literature51. They each undertook investigations independently and almost contemporaneously in the mid 1860's. Herbst was convinced of the source of infection in these dogs and speculated that.Leuckart. But these achievements only came after a false start induced by a theory of Friedrich Küchenmeister. spiralis and. abundant worms were found in the muscles of both dogs. however. Since he was about to leave for Norway. This van Beneden undertook to do. In the meantime.580 A History of Human Helminthology and dogs. Zenker independently found adult worms in the small intestine of a human111. In 1857. On microscopical examination of the mucus. Leuckart fed trichinous flesh to pigs. but in view of Kuchenmeister's assertions. STUDIES ON THE MIGRATION AND DEVELOPMENT OF LARVAE When Herbst transmitted experimentally infection from a badger to dogs. He found a dozen mature Trichuris in the bowel and. At the same time as Leuckart confirmed Virchow's observations in experimental animals. in translating Leuckart's letter from the German. in accordance with Küchenmeister's hypothesis. there was difficulty in deciphering his handwriting and a French version was not published until 7 November 1859103. Virchow found swarms of lively nematodes 1-2 mm long within which he could see eggs or sperms. He despatched word of this observation to PJ van Beneden in Louvain. When the intestines were examined macroscopically at autopsy. the only parasites apparent were tapeworms. Virchow merely concluded cautiously that muscle trichinellae are able to continue their development in the intestinal tract of a carnivorous animal. but on this occasion waited five weeks before examination of the intestines. three and a half days later it died. Leuckart repeated his studies and infected a number of dogs and cats. and thus it was printed on 26 September 185964. however. Leuckart took these to be the sexual form of T. and in a true spirit of scientific enquiry. in an exemplary and forthright fashion. as will be described later. he had found that the larvae had escaped from their capsules and doubled in size63 . inadvertently mistook "duizend" (dozen) for dutzend (thousands). he fed trichinous meat to a dog. Virchow made known his results at a meeting of the Berlin Medical Society on 1 August 1859 102 then sent a written account to the Academy of Sciences in Paris. asking him to communicate these results to the Academy of Sciences in Paris. spiralis. but. and all four of them began experimental studies using this material. he reported that when he had examined the intestinal mucus of mice shortly after ingestion of such cysts. In 1859. According to Reinhard88. he searched without success for Trichuris adults that might have developed from ingested trichinellae. He found the fullgrown worms described by Virchow in the intestines of these animals and. Rudolf Virchow had not been idle. however. Zenker sent portions of trichinous muscles from this person to Leuckart. he remarked that: the greatest difficulty lies in explaining the process by which the very small and very . These parasites did not resemble Trichuris at all. His detailed paper followed the next year104 On receipt of this information. Leuckart declared that Virchow was absolutely right65. Luschka and Virchow. In July 1859. and equal distribution of the trichinae through all voluntary muscles justifies the assumption that their eggs have been carried to the respective places of settlement by means of the blood circulation. Leuckart discovered that female adult worms were viviparous and released minute filariform embryos that immediately penetrated the intestinal mucosa then passed to the muscles. spiralis 66. Like Leuckart. Leuckart and Zenker provided the clue to the solving of this question. from the dog. because of his great authority. this view held sway for many years. He passaged the worms through five successive generations and found that the severity of illness and the likelihood of death was dependent upon the size of the inoculum of infective larvae. Uncertainty has surrounded the relationship between intestinal adult worm numbers and muscle worm burdens. Meanwhile. since the ample. Although the development of adult worms in the gut and of infective larvae in the muscles was fairly well understood. Leuckart66 held that the larvae reached the muscles via the connective tissues and. Nevertheless. For example. Leuckart made two further important observations. Initially. In his series of experiments. Virchow105 had found larvae in the mesenteric lymph nodes. Unfortunately. although he was not able to prove this point. he noted that the cyst was first seen four to five weeks after infection and that the muscle fibres then atrophied105. but solidly formed particles representing worm eggs have been able to enter the blood vessels from the intestinal cavity. there was considerable doubt as to the manner in which larvae passed from the gut to the muscles. He then studied the development of larvae and showed for the first time that they were located not between the muscle fibres.Trichinosis 581 elastic. adult worms were mere transients in the bowel. simultaneous. there were voices of dissent. Virchow observed that trichinellae were larviparous and found larvae within seven days of ingestion in the mesenteric glands and the serous cavities. he found that the worms penetrated the fasciculi and within the space of 14 days acquired the size and structure of the well-known T. as had been previously thought. Leuckart blotted his copybook by declaring that it could scarcely be doubted that Man acquired his trichinellae. In addition. There. Virchow was independently pursuing his own studies. adult worms had moved from the small intestine to the colon prior to expulsion. Firstly. by the twelfth day after infection.53 The discoveries of Virchow. Final proof that larvae may travel via the bloodstream was provided by Herrick and Janeway who in 1909 found newborn larvae in the blood of a woman suffering from trichinosis 54. but within them. but he could not find them in the bloodstream. Secondly. thus suggesting that the worms might find their way into the bloodstream. like echinococci. he found that in contrast to muscle larvae. This view was supported by Zenker111 and sustained by Fiedler43 who found larvae in the right heart of experimentally infected rabbits. It has never been defined clearly in humans how many muscle larvae are produced for each adult worm in the gut . he fed trichinous flesh to rabbits and found that they died five to six weeks later as a consequence of muscular degeneration. Bartholomew's Hospital dissecting room in 1835.42 . a practitioner in Bristol. and in all cases. Wood wondered whether the patient had had trichinosis. the individuals themselves appear to have been unaware of their presence.300 muscle larvae are produced per female adult worm91. Whether or not immunity to reinfection develops in humans has never been clearly shown.. in those who have died from chronic diseases attended by atrophy. Publication of Owen's paper induced Henry Wood.. Owen remarked that although there were vast numbers of parasites in the voluntary muscles. He died a few days later and post-mortem examination disclosed pneumonia. When he read Owen's paper. Wood was unable to make out their nature. and in those who have been cut off in robust health by some violent accident. Furthermore. He concluded that "it is not improbable that in all cases the patient himself will be unconscious of the microscopic parasites which are enjoying their vitality at his expense"76. was more cautious. but it was eventually shown in experimentally-infected guinea pigs that approximately 1. No symptoms have been in any case manifested during life which could lead to the supposition of their existence. Paget.. on the other hand. neither person had any symptoms referable to the muscular system. A 22 year old man had been admitted to the local infirmary in October of the previous year with "acute rheumatism" of the trunk and extremities.(if) there was any symptom or inflammation of any kind in the muscular system"108 in retrospect in patients in whom trichinellae were found at autopsy. Despite observing the latter with a microscope. Wood's was a voice crying in the wilderness and Farre in 1850 expressed the consensus of opinion when he wrote that trichinellae: have been found equally in the diseased and in the healthy. this resistance can be partially transferred with immune serum36 and with immune lymphoid cells60 and is directed against both the larval stages in the muscles as well as against the worms in the intestines29. so as to see whether they accompany any particular illness"81. It has been shown in such animals that considerable resistance is induced by natural infection71 and after immunization with Trichinella antigens72. England to challenge Owen's view and describe a patient who in retrospect may well have had symptomatic trichinosis.582 A History of Human Helminthology during the course of an infection. noting in his private letter to his brother Charles on 11 February 1835 that "their immense numbers may prove important when more cases have been found and compared. however. RECOGNITION OF THE CLINICAL FEATURES In his discussion of the two patients who were found to be infected in the St. Nevertheless. He therefore suggested that it may "be well to ascertain. pericarditis and multiple punctate lesions in the muscles. but extrapolation from animal experiments suggests that some resistance probably develops. Despite the absence of splenomegaly. but this patient also enabled him to make some important contributions to the understanding of the zoology. Zenker ascertained the source of infection in this patient. this observation led him to conclude rightly that they were embryos infiltrating the muscles. It was rapidly accepted that the severity of the clinical manifestions was dependent upon the intensity of the dose of infective larvae30. Recovery in the survivors was rarely followed by any permanent sequelae. pathogenesis and epidemiology of this infection. thirst and painful abdominal distension. He was astounded to find in his first glance at the first microscopical preparation. abundant sexually mature worms that were identical with those described shortly before by Virchow. most patients feeling well within several . This was followed by the appearance of pulmonary symptoms. a provisional diagnosis of typhoid fever was made whereupon she suddenly developed severe pains in. Moreover. thought to be consistent with a diagnosis of typhoid fever. the muscles which prevented her from flexing her knees or elbows. the muscle fibres were extensively degenerated. myocarditis. he found. (East) Germany under the care of Dr Walther. Zenker's discovery was followed by reports of a number of epidemics of trichinosis. and she died on 27 January. the only other discernible abnormalities being bronchopneumonia and intestinal inflammation. She had become ill two weeks previously when she complained of great fatigue. on careful examination of the musculature.000 larvae per gram49. encephalitis and renal damage in addition to the usual gastrointestinal and muscle disturbances23. Not only did Zenker demonstrate the potential clinical importance of trichinosis. nothing could be found to substantiate a diagnosis of typhoid fever. probably reaching that site via the bloodstream. Firstly. On complete post-mortem examination. On 12 January of that year. a 20 year old servant girl was admitted to hospital in Dresden. samples of her muscles were examined by Friedrich Zenker who was particularly interested at that time in the pathological changes occurring in muscles during typhoid fever. again in the first drop. and marked swelling of. Prior to formal autopsy. he found some larvae that were smaller in size but similar in form to the usual trichinellae. when he examined a sample of this material two weeks later. Secondly. as will be recounted later. Further examination showed that all the muscles were permeated in this way by massive numbers of worms.Trichinosis 583 All this changed dramatically at the beginning of 1860. Only the most heavily infected persons died and these often developed features of pneumonia. dozens of unencysted trichinellae lying free in the muscle parenchyma. as will be described later. One study later calculated that patients with <100 larvae per gram of muscle were likely to be asymptomatic whereas severe clinical manifestations was probable if there were >1. he had put aside a portion of intestinal mucus obtained at autopsy. Zenker was in no doubt that the patient had died from a trichinous invasion of the musculature 111. Thirdly. This was the first time that adult worms were found in a human. 584 A History of Human Helminthology months21. When these cysts were fed to rabbits. spiralis cyst was found in an intercostal muscle of a 3. (West) Germany. who found parasites in a fragment of muscle taken from a butcher44. This had been successfully achieved by Zenker and Waldeck by 1862113. An alternative approach was to demonstrate larvae in muscle biopsies. Finally. This has remained the method of choice for the diagnosis of trichinosis to the present day. This was first achieved in 1909 by Herrick and Janeway54 who investigated a small family outbreak of trichinosis. although it suffers from the twin disadvantages of necessitating the subjection of a patient to a biopsy and the probability of finding a worm being dependent upon the size of the specimen removed and the intensity of infection. confirmation of the diagnosis depended upon demonstration of the parasite. For example. This was suggested by Küchenmeister in 186159. Nevertheless. This was despite the continuing presence of infective larvae in the muscles which may remain viable for many years. Salzer94 claimed that he had found T. DEVELOPMENT OF DIAGNOSTIC METHODS It was soon realized that a diagnosis of trichinosis could be suspected on clinical grounds in a patient who had features resembling those of typhoid fever except that a rash and splenomegaly were replaced by severe muscle pain and swelling. encysted trichinellae were found at autopsy in the muscles of a man who had died in the Vienna Krankenhaus (Hospital). For example.200 year old Egyptian mummy buried in the Valley of the Kings across the river Nile from Luxor24. trichinellae developed in the gut and muscles100. calcified. this method of diagnosis has fallen out of favour and is rarely mentioned in modern textbooks. The third method depends upon observing larvae in the peripheral blood. trichinellae could be sought in the faeces. Another laboratory investigation which may point towards the diagnosis of . it has been claimed that a T. Enquiry revealed that 26 years previously he had suffered from a severe attack of "rheumatism" that had kept him confined to bed for several months. Using this technique. larvae have been found in the cerebrospinal fluid16. larvae were found in the blood of the mother 23 and 25 days later but not in the children's blood. but this is not a standard diagnostic technique. A mother and seven of her children ate contaminated pork chops on 24 February of that year. Nevertheless. spiralis larvae in the blood of 9 out of 14 patients. There were a number of ways in which this could be done. This diagnostic method became popular and successful in the early part of this century. then the value of the technique was proven in the following year by Friedreich of Heidelberg. but subsequent experience showed that it was an unsatisfactory method because such worms were few in number and were present only early in the illness. Firstly.68. 20. as well as the induction of delayed hypersensitivity reactions after intradermal injection of antigen into these animals19. that it is therefore the only rational remedy which can be employed in trichina disease in man. Although alcoholic extracts of this material were not promising. Bachman introduced an improved antigen with which he was able to demonstrate the presence of precipitating antibodies in the serum of experimentally-infected rabbits and guinea pigs. (West) Germany in 1864 convinced himself that: benzine is of all the remedies the best anthelmintic and that it may be taken by man in large doses. Indeed. He prepared an extract of Trichinella antigen from trichinous meat after digestion of the muscle fibres with pepsin and hydrochloric acid.it destroys the trichinae in the intestines and thereby prevents the spread of their embryos. This was first observed in 1896 by Thomas R Brown. Despite refining of techniques.37. This was followed by the demonstration that such antibodies could be found in the serum and that similar skin reactions occurred in humans with trichinosis18. but the approach was scarcely feasible in the vast majority of instances since the diagnosis was rarely made before the adult worms in the gut had done their damage seeding the muscles and then been largely expelled. a medical student at Johns Hopkins University. Ströbel in 1911 was the first to investigate these possibilities.73 The concept was rational enough. Baltimore. this is a problem which has bedevilled the anthelmintic therapy of trichinosis to the present day. USA. who found a marked eosinophilia in a 23 year old man six or seven weeks after the onset of the symptoms of trichinosis25. nor are they able to quantify the intensity of infection. turpentine and Glauber's salts were tried 30. immunological tests have remained of limited value as they are not able to differentiate between recent and long-standing infections17. caustic soda and antiformin extracts yielded antigens which gave positive complement fixation reactions with sera from infected humans and experimental animals97. it is of limited diagnostic value since eosinophilia is common in other tissue helminth infections as well as a in variety of unrelated conditions. Greater diagnostic specificity was sought by employment of immunodiagnostic techniques. Logically enough... the effects of various purgatives such as calomel.. THE SEARCH FOR EFFECTIVE TREATMENT The initial attempts to treat trichinosis were directed towards accelerating expulsion of the adult worms from the intestines. Although much has been made of this observation by a number of American writers.Trichinosis 585 trichinosis is the appearance of an increased number of eosinophils in the blood. A multitude of anthelmintic drugs were tried in trichinosis but were found to be uniformly . Professor Mosler of Giessen. Zenker found numerous encysted T. In any case. Nevertheless. therefore. but the value of such a regimen remains to be proven. He reasoned. Thus. Sporadic cases of illness or death attributed to trichinosis were reported following Zenker's detailed description and a mild epidemic was recognized in .586 A History of Human Helminthology unsuccessful until Campbell and Cuckler in the early 1960's showed that the new benzimidazole. he realized that trichinellae go through their whole cycle of development in one and the same host. some of the original ham was still available and on microscopical examination of it. a controlled trial of thiabendazole in human trichinosis does not appear to have been done. that infection was likely to have been acquired by consumption of trichinous meat. This drug was then used on an infected woman who. eliminated intestinal worms and killed many muscle larvae in infected pigs27. it is doubtful whether any agent effective against muscle larvae will be of much benefit as much of the damage will already have been done before the diagnosis is made and treatment instituted85. it became clear that humans were infected by eating trichinous pork and that infection presumably passed from pig to pig by consumption of trichinous scraps. thiabendazole. An alternative approach was tried by Salzer in 1916 who gave serum from previously infected persons to two patients. improved96. he claimed that this procedure produced a fall in temperature and in the level of eosinophilia 94. although he was aware that she was fond of picking at food. (East) Germany where the dead woman had come from and interviewed the owner of the estate.28. particularly as it may inhibit immunological expulsion of worms from the gut and thus lead to even greater numbers of muscle larvae. he went to the nearby village of Plauen. spiralis larvae111. UNDERSTANDING THE EPIDEMIOLOGY When Zenker found mature worms in the intestines of his patient. Further enquiry revealed that the owner of the estate and the housekeeper had both been ill with an abdominal complaint in early January and the the butcher had been extremely ill. being confined to his bed for three weeks with fever and a paralysing weakness. Although some success was claimed at first. whether coincidentally or not. Consequently. the value of such therapy is probably small. but immunological treatment has not found a place in the management of trichinosis. This was followed by experimental studies in trichinous animals50. Fortunately. This could probably be overcome by the simultaneous administration of thiabendazole. The farmer indicated that he had ordered a pig to be slaughtered on 21 December but could not say whether the servant girl had eaten any raw meat. The realization that the inflammatory reaction around muscle larvae was responsible for producing many of the ill effects of trichinosis led to trial of ACTH69 and corticosteroids 90 in the alleviation of symptoms. or added it in small pieces to larger joints of pork to make up weight.000 inhabitants near the Hartz mountains in (East) Germany. Unfortunately. When some of the patients developed pneumonia and evidence of muscle inflammation. the manufactory closed. Muscle biopsies were taken from several of the victims and larvae of T. He made this confession shortly before his death. The number of persons so afflicted rapidly increased and there was great alarm and apprehension that an epidemic of typhoid fever was impending. which was caused by trichinosis contracted from his own meat. Included on the menu were Röstwurst und Gemüse (roast sausages and vegetables). a review was made of the epidemic which had occurred in 1849 in Wegeleben. Upwards of 200 convalescents were wandering about without work. Most of the diners became ill and over 20% of them died. the steward sold a sickly pig contrary to his employer's instructions. fell ill and 102 of them died4.8 Following the outbreak of trichinosis in Hedersleben. The remnants of the sausages were examined microscopically and found to be swarming with encapsulated trichinellae.8 The background to this outbreak has been recorded most graphically: All this havoc has been caused by one trichinous pig! The butcher. The Röstwurst had been ordered from the butcher a number of days previously in order that it could be properly smoked. A number of . His wife also died of the disease. most of them young. Zenker's report was remembered.Trichinosis 587 Plauen in 1862. several persons who had been at the dinner were attacked with diarrhoea. even worse was to befall the town of Hedersleben in Germany two years later in 1865. The pig was duly killed and the pork worked into sausages which were then smoked and delivered to the hotel where they were in turn fried and served to the guests at the dinner table. saying that: the place was almost deserted.100 people. a small town of about 6. Just over 100 people attended a dinner in a hotel in the town in order to celebrate the fiftieth anniversary of the battle of Leipzig. 398 persons. had carefully disguised it by mixing it with the meat of two healthy pigs. in which 160 persons had been affected and 30 had died. Biopsies of muscles from some of these people who were still alive showed that that epidemic had also been caused by T. prostration and fever. In this small village of 2.8. spiralis were found in all stages of development. having recognised the abnormal appearance of the meat of this pig. Awful though this was. abdominal discomfort. A number of others in the town were also infected with this pork. and that 90 orphans were weeping over the graves of their parents. an outbreak of trichinosis occurred in Hettstadt.3. The butcher went to a neighbour and bought a pig from his steward. and bearing in their features traces of the fearful malady. A visitor to the town soon afterwards has described the scene. the diagnosis of trichinosis being confirmed at autopsy1. In October of that year.57. eventually nearly 150 became ill and 28 persons died. but it was not until 1863 that the full import of trichinosis impressed itself upon the minds of both the medical profession and the public at large. a community located about half a mile away. On the following day. spiralis 93. there were 13 major epidemics of trichinosis in Saxony alone between 1860 and 1876 with 1. then appropriate measures had to be encouraged and. Taenia solium. but with improving public health control measures and agricultural methods.588 A History of Human Helminthology other epidemics in various parts of Europe were also diagnosed in retrospect. Similar studies in France by the same observers found little evidence of trichinosis. The prevalence of infection in humans was investigated in Leipzig. Similar epidemics have since been noted in many other parts of the world. though he divide the hoof and be clovenfooted. they have declined in both frequency and severity. self-righteously observed that trichinosis was most prevalent in Germany because "the otherwise abstemious inhabitants of the Fatherland display a remarkable fondness for chopped pork"30. Professors Delpech and Reynal of France were charged with studying trichinosis in Germany. minced pork6. (East) Germany where 6 in every 100 persons coming to autopsy were found to be infected. that if they were able to connect pigs and human illness at all. Indeed. then the tapeworm. In many places. Understanding of the mode of transmission opened up means for the prevention of infection. Despite the institution of control measures. however. In places where infection was common. spiralis. spiralis. policed. and the Englishman. spiralis by consumption of contaminated meat. Austria. "and the swine. although with much less certainty.266 people being afflicted12. found it more convenient to eat raw. Cobbold. yet he cheweth not the cud. public health policy and political considerations . was responsible as this parasite is at least visible macroscopically. as evidence that the Israelites recognized the relationship between trichinosis and swine. such as Dresden. rats inhabiting the slaughterhouses were often infected with T. the use of raw meat had become very common in Prussia and Saxony because workmen. Authorised Version). The prevalence of infection in both animals and humans needed to be ascertained. especially pork. The Mosaic prohibition was perpetuated in Islamic law and has undoubtedly serendipitously prevented many Muslims from being infected with T. (East) Germany and Vienna. methods had to be found for the destruction of muscle larvae. In the wake of the outbreak of trichinosis at Hedersleben. In the following year. THE EVOLUTION OF PREVENTIVE AND CONTROL MEASURES The recognition that humans became infected with T. It seems more likely. having no means of cooking or else not taking the trouble to do so. caused some to look backwards and seen the Mosaic interdiction (Leviticus 11: 7. if necessary. they presented their pioneering report in which it was concluded that every clinical case had been caused by eating imperfectly cooked pork7. he is unclean to you". When he killed a pig. It is only the doctors without practice who make a noise about them in order to create some occupation for themselves. thereupon disposed of it amongst his own family13. A Prussian ministerial journal asserted that "trichina-disease" was nothing but a revolutionary proceeding propagated by the enemies of the government 6. Vain hope!"8 It appeared at that time that the prevention of trichinosis was founded upon two practical propositions . Virchow addressed a meeting of town councillors. This was done in many parts of Germany and between 1864 and 1874. assured that the pork was fit to eat. A hope was expressed that the illness was not caused by trichinae in the sausage of which he had been badgered to swallow a piece. This was done by compressing . The meeting calls upon him to eat. Whereupon M. doctors and a sprinkling of the general public shortly before Christmas 1865 on the prevention of trichinosis.recognition of infected meat and the cooking of pork sufficiently well to kill the worms. Dr. 'He had not spoken of Berlin doctors (Eat! Eat!).' &c. finding that the trade was almost extinguished. Kuhne of Halle in (East) Germany had shown in his report to the Prussian government that it was frequently not possible to recognize a trichinous pig9. was ill. (Great interruption. voted 200 to 9 in December 1865 to make arrangements for microscopical examination of all pork and petitioned the municipality to make such examinations obligatory upon them all8. then he felt perfectly easy in his mind and.to his pastor then await the consequences for 14 days. At the conclusion of his speech. Urban suddenly seizes the sausage on the president's table. he said. This technique not being generally applicable. Urban. If the pastor remained healthy. Drs. He was confined to his bed and his arms and legs were paralysed. butchers. However. he was careful to send a portion of it . Eventually. Urban wishes to explain.ham or sausage . Urban. the butchers of Berlin.Trichinosis 589 became inextricably linked. and leaves the hall forthwith. The (undoubtedly apochryphal) story has been told about how a Holstein peasant solved this problem. What happened next has been recorded in The Lancet: Thereupon a veterinary practitioner. Mason challenges Urban to eat some of the sausage on the President's table (Great applause). Prof. 'Trichinae'. In another incident. he handed to the president of the meeting a piece of smoked sausage and a piece of meat from a pig which had been recognized as trichinous. the president is obliged to stop the veterinarian). amidst the applause and laughter of the assembly. rose and combated all that science had acquired during the last five years as an unfounded illusion. with any such products found to be infected being confiscated. bites off a piece and eats it. the Oelkszeitung reported that the veterinarian. of the name of Urban. He would first see if the sausage contained trichinae. Virchow and Mason demand an apology from M.' (Great laughter and continued shouts of Eat! eat! eat!). About five days later (on 23 December). but of those at Hedersleben (Eat!). not everyone believed that trichinosis was a serious problem. thorough microscopical examination by government inspectors of pork products for sale was commonplace throughout Germany. 623 infected pigs were found and withdrawn before human infection could occur11. 'are the most harmless animals in the world. The economic consequences of these actions were such that the United States Congress in 1890 passed an act requiring microscopical examination of all pork destined for export. however. Sixteen per cent of 11. In 1952. German inspectors found that another 1% were still infected. 4-6%. Hungary and Italy prohibiting the importation of porcine products from the United States. acted in good faith for both he and the butcher partook of the infected meat and suffered in consequence 15. 10-20% 46. a viral infection of swine. (West) Germany. who remained sceptical. the Supreme Court of Prussia found a butcher guilty of manslaughter because he sold trichinous meat which caused the death of a person. On subsequent examination of the remaining certified pork.4% were eliminated as being trichinous 46. There were some. Portugal and Spain. ordinances were passed in Austria. Germany reinstated the prohibition which had been repealed in 1890 on the initiation of testing. there is little doubt that the inspector.5%. 1-1. the meat not having been examined microscopically 11. 0. . A vivid demonstration that microscopical examination could not be relied upon occurred at Emersleben in Germany in 1883. By the end of the decade. Reinhard88. then a similar decree was proclaimed in the following year in Germany. Extensive post-mortem surveys were undertaken in the USA to define the prevalence of infection in humans and in swine. Studies of swine showed that the frequency of pigs infected with this parasite depended upon the method of feeding them. the majority of European countries forbade the importation of American pork. Although incompetent. believed that not only was microscopical examination inaccurate. Norway. those given uncooked garbage. In one instance. Much of this pork was exported to Europe in the form of hams and sides of bacon. broke out which led to legislation requiring that pigs grown for commercial use be fed cooked garbage or grain. more than 8 million carcasses were examined and 1. Out of a population of 700 persons. it became apparent. a barber.5%. some worms remained viable as was indicated by the outbreak of trichinosis which occurred in Bremen. those fed on cooked garbage or allowed to forage in the open fields and woods. In 1879. that trichinosis was not uncommon in the United States of America10. and those permitted to feed on slaughter-house offal. In September of that year. killed it on the 12th and sold its flesh from the 13-19th of that month. a severe epidemic of vesicular exanthema. In the 1870's. but that the frequency of trichinosis in swine was so small as to not justify the effort made at its detection. Despite being strongly salted and dried. for example. a butcher bought a pig. Consequently. 250 were attacked and 42 died. after consumption of sides of imported American pork.590 A History of Human Helminthology fragments of meat between two plates of glass and searching for parasites with the aid of a magnifying glass or the low power lens of a microscope. Between 1896 and 1906.000 human cadavers examined between 1931 and 1942 were infected. following several epidemics of trichinosis in humans and the demonstration that 3-16% of the pigs in Indiana were infected. those fed principally on grain. 1866 6. ANONYMOUS. 1928 20. ANONYMOUS.Trichinosis 591 This resulted parenthetically in the prevalence of trichinosis in the pigs falling from 0. 1943 18. ANONYMOUS. ANONYMOUS. 1866 5. The new disease. Trichinae. Journal of Preventive Medicine 2: 513-523. but this technique has not found widespread commercial application. ANONYMOUS. BACHMAN GW. 1864 2. Lancet ii: 843. Trichinae in the cerebrospinal fluid. ANONYMOUS. British Medical Journal i: 76. 1864 4. 1881 15. Lancet i: 163. emphasizing that the only sure prophylactic measure is thorough cooking of all meat before ingestion46. Lancet ii: 295. Lancet i: 76. British Medical Journal i: 75-77. REFERENCES 1. Residual symptoms in patients following recovery from acute infestation . Final report. other sources of infection have sometimes occurred. or trichiniasis. ANONYMOUS. 1866 8. Salting was found to often render meat innocuous. Lancet i: 100-101. Similarly. 1877 13. British Medical Journal ii: 395. Precipitin and skin tests as aids in diagnosing trichinosis. spiralis has been found in nearly 60 different species of mammals. British Medical Journal ii: 714. The other feasible prophylactic measure was proper preparation of meat to ensure destruction of larvae. Eventually. Despite the marked association between human trichinosis and the consumption of infected pork. T. British Medical Journal i: 342. Trichina epidemics. ANONYMOUS. in Germany. Recent outbreaks of fleshworm disease. 1866 9. Trichinosis. 1916 17. British Medical Journal i: 287. 1876 12. Scientific report on the trichina. 1932 19. ANONYMOUS. ANONYMOUS. BACHMAN GW. Occasional localized outbreaks of human trichinosis have followed the consumption of a variety of contaminated meats ranging from polar bear to white whale.95% in the 1930's to 0. but this was unreliable since the time necessary to achieve killing of larvae was uncertain and variable14. Finally. British Medical Journal i: 118-119. THEILER H. New test for trichinae. Trichinosis. Lancet ii: 240. ANONYMOUS. irradiation has been shown to be effective47. 1864 3. and in humans from 16% to 4% in 1966-8 115. Cooking by boiling was the most effective method if continued for long enough but quick roasting leaving the central parts of the meat red was of little avail. 1875 11. 1866 7.12% in 1961-5 114. ANONYMOUS. Lancet i: 385. British Medical Journal i: 375-376. British Medical Journal ii: 492-493. A precipitin test in experimental trichiniasis. Journal of Preventive Medicine 2: 35-48. 1866 10. 1884 16. ANONYMOUS. ANONYMOUS. Trichiniasis. BERCOWITZ Z. Benzine and trichinosis. AUGUSTINE DL. ANONYMOUS. Parasitology 24: 60-86. The last new disease. ANONYMOUS. Lancet i: 16. smoking could not be trusted to decontaminate meat. Trichinosis. it was shown that refrigeration at -15o C for 20 days was also an effective means of killing larvae87. ANONYMOUS. 1880 14. An intradermal reaction in experimental trichiniasis. 1928 21. Laboratory tests for trichiniasis. SCOTT JW. BLUMER G. Autopsy of an Egyptian mummy . PAGENSTECHERHA. BETHELL FH. COBBOLD TS. Archives of Internal Medicine 22: 601-609. 130-131. 174-177. Annals of Tropical Medicine and Parasitology 56: 500-505. pp 116. 1971 47. 1962 29. FRIEDREICH N. On the discovery of Trichina. American Journal of Tropical Medicine 20: 849-857. 1866 32. BISCHOFF TL. CAMPBELL WC. KAPLAN SS. HALL MC. 1863 38. WIGDOR M.592 A History of Human Helminthology with trichinosis. Archiv für Anatomie und Physiologie und für klinische Medicin (Virchow) 25: 399-413. London Medical Gazette 17: 382-387. Lancet ii: 1056. 1975 39. 1862 45. 1918 51. Systema Helminthum. A study upon passive immunity in experimental trichiniasis. Experiments with Trichina spiralis. Die Trichinen. FARRE A. 1849-1851 40. Bulletin of the History of Medicine 53: 520-552. 1897 26. 1977 25.ROM I: trichinosis. Thiabendazole treatment of the invasive phase of experimental trichinosis in swine. Parasitology 30: 156-166. Johns Hopkins Hospital Bulletin 8: 79-81. Studies on trichinosis. Abstracted in Lancet i: 424-426. HELLER A. Journal of the American Medical Association 154: 653-658. 1962 28. Lehrbuch der pathologische Anatomie der Hausthieren. GURET. On the discovery of Trichina. COBBOLD TS. 18: 58-59. Archiv der Heilkunde 5: 1-29. pp 480. The dual antibody response to experimental trichinosis. 1882 36. Owen and the discovery of Trichinella spiralis. GOULD S E.. COBBOLD TS. American Journal of Clinical Pathology 55: 2-11. Lancet i: 224-225. HALL MC. III. 1956 30. An experimental study of serum therapy in trichinosis. 1865 46. Effect of thiabendazole upon experimental trichinosis in swine. 1979 27. Histoire naturelle des helminthes ou vers intestinaux. Beiträge zur Entwicklungsgeschichte der Trichinen nebst einigen Mittheilungen über die Einwirkung einzelner Medicamente und anderer Agentien auf dieselben. Vindobonae. Paris. Studies in trichinosis. Cited in 99 43. DUJARDIN F. Faits et considérations sur la trichine (Pseudalius trichina). 1882 35. DAVAINE C. American Journal of Pathology 78: 477-496. Berlin. Observations on the Trichina spiralis. 1864 31. 1940 22. Cyclopaedia of the Practice of Medicine. DIESING CM. de BONI U. Public Health Reports 52: 539-551. 1845 41. London. DESPOMMIER DD. Leipzig. W Engelmann. pp 1267. 1867 34. volume . Canadian Medical Association Journal 117: 461-473. Ein Beitrag zur Pathologie der Trichinenkrankheit beim Menschen. COBBOLD TS. GOMBERG HJ. 1936 24. CUCKLER AC. The complex clinical picture of trichinosis and the diagnosis of disease. Gazette Médicale de Paris. Heidelberg 6: 232-250. Ein Fall von Trichina spiralis. LENCZNER MM. COLLINS BJ. Proceedings of the Helminthological Society of Washington 23: 49-58. FIEDLER CL. FARRE A. 1849 49. BROWN TR. 1938 37. 1864 44. Librairie Encyclopédique de Roret. CHUTE RM. pp 654. Control of trichinosis by gamma irradiation of pork. In. Adaptive changes in muscle fibres infected with Trichinella spiralis. two volumes. COBBOLD TS. Lancet ii: 911. H von Ziemssen (editor). COBBOLD TS. 1835 42. CAMPBELL WC. The story of trichinosis. New England Journal of Medicine 214: 1229-1235. Wilhelmum Braumüller. The discovery of Trichina spiralis. 1840 23. FUCHS CJ. History of trichinosis: Paget. CAMPBELL WC. Nach Versuchen im Auftrage des Grossherzoglich Badischen Handelsministeriums ausgeführt am zoologischen Institute in Heidelberg. 1863. Groombridge and Sons. 75-78. pp 144. Proceedings of the Society of Experimental Biology and Medicine 110: 124-128. Trichinosis with special reference to changed conceptions of pathology and their bearing on symptomatology. Medicinishe Ann. CULBERTSON JT. 1866 33. 1937 50. GOULD SE. The discovery of Trichina spiralis. third series. Lancet i: 291. CUCKLER AC. Journal of the Linnean Society 9: 205-212. 1954 48. Entozoa: an introduction to the study of helminthology with reference more particularly to internal parasites of man. two volumes. Annotation to a German translation of reference 74. 62. Zur Naturgeschichte der Trichina spiralis. 74. 1978 KRATZ F. Königliche Gesellschaft der Wissenschaften. London. 1935 MOSLER. Immunity of rats to reinfection with Trichinella spiralis. Philadelphia 3: 107-108. Eine vorlaüfige Mittheilung. Transfer of lymph node cells. Artificial immunization of rats against Trichinella spiralis. Ein Lehr. I. pp 677. Tropical medicine and parasitology. 1951 LUSCHKA H. Journal of the Elisha Mitchell Society 80: 133-135. 1851 McCOY OR. Abstracted in British Medical Journal ii: 402-403. p 228. 1866 KüCHENMEISTER F. 56. Description of a microscopic entozoon infesting the muscles of the human body. Comptes Rendus Hebdomadaires des Séances de l'Académie des Sciences 49: 453-457. American Journal of Hygiene 21: 200-213. Archives of Internal Medicine 3: 263-266. Chronic infectious diseases. pp 486. 58. 73. 1851. 1862 LARSH JE. 71. Translated in 56 HERRICK WW. Journal of the American Medical Association 66: 1856. Wilhelm Engelmann. WEATHERLY NF. Leipzig. 1931 McCOY OR. BG Teubner. pp 452. The Sydenham Society. On animal and vegetable parasites of the human body. GOULSON HT. Nachrichten von der Georg-August Universität. 1853. The Sydenham Society. MOTT KE. 65. Translated in Quarterly Journal of Microscopical Science 8: 168-171. Animal parasites belonging to the group Entozoa. probably depending upon the formation of very small cysticerci. 1866 LEUCKART R.Trichinosis 593 52. 54. 1964 LEIDY J. two volumes. Secretary's abstract. 1860 LEUCKART R. translated by AH Buck. A manual of their natural history. Demonstration of the Trichinella spiralis in the circulating blood in man. Zeitschrift für rationeile Medicin 8: 259-262. Deutsche Klinik 13: 367-368. translated by E Lankester. Der geschlechtrsreife Zustand der Trichina spiralis. The effect of ACTH in trichinosis: a clinical and experimental study. Die Trichinenepidiemie zu Hedersleben. Göttingen. Die in und an dem Korper des lebenden Menschen vorkommenden Parasiten. Classic investigations. Nachrichten von der Georg-August Universität. London. 1857 KüCHENMEISTER F. Physiologie und wissenschaftliche Medicin. JANEWAY TC. 67. 60. 1860 LEUCKART R. Cited in 31 LINTZ W. Expériences sur la trichina spiralis (ce ver devient un trichocéphale dans l'intestin du porc). Notes of a peculiar appearance observed in human muscle. Untersuchungen über Trichina spiralis. Philadelphia 10: 9. Leipzig. pp 125. 1860. 1835 HERBST M. Archiv für Anatomie. 53. 1833 KEAN BH. Göttingen. Cited and partly translated in 2 OWEN R. 72. 70. Cornell University Press. Secretary's abstract. 69. London Medical Gazette 16: 125-127. Abstracted in Quarterly Journal of Microscopical Science 1: 209-211. 334-335. Zeitschrift für wissenschaftliche Zoologie 3: 69-79. 1835 . Studies on delayed (cellular) hypersensitivity in mice infected with Trichinella spiralis. Beobachtungen über Trichina spiralis. 1857 LEUCKART R.und Handbuch der Diagnose und Behandlung der thierischen und pflanzischen Parasiten des Menschen. New England Journal of Medicine 245: 757-760. Ithaca. REID DH. 66. Bericht über die Leistungen in der Naturgeschichte der niedern Thiere wahrend des Jahres 1856. American Journal of Hygiene 14: 484-494. Ueber Trichinen. 64. 3. Proceedings of the Academy of Natural Sciences. 1909 HILTON J. 55. 63. 68. pp 260-264. 1846 LEIDY J. Translated in Quarterly Journal of Microscopical Science 8: 168-171. Entozoon in the superficial part of the extensor muscles of the thigh of the hog. Trichinosis and the cerebrospinal fluid. 61. 1855. 57. 1861. London Medical Gazette 11: 605. 59. 1859 LEUCKART R. WEISS WW. Archiv für Naturgeschichte 23: 165-272. Remarks on Trichina. Volume 1. diagnosis and treatment. Königliche Gesellschaft der Wissenschaften. 1875 HENLE. Proceedings of the Academy of Natural Sciences. 1860. pp 135-138. 1916 LUONGO MA. RUSSELL AJ. pp 615-660. pp 438. 1882 79.594 A History of Human Helminthology 75. very similar to 76. 1882 80. The discovery of Trichina spiralis. Notes of interesting cases occurring in medical practice. pp 23-37. Deutsch Klinik 11: 430. STONE CT. ROUPELL G. STRöBEL H. Cited in 84 84. TURNER DF. Memoirs and letters of Sir James Paget. Lancet i: 270. PAGET S. Braun Schweig. very similar to 74. deposition and growth of the larvae of Trichinella spiralis and their significance in the chemotherapy of the infection. Parasiten. Identical with 77. 1865 94. Identical with 74. von SIEBOLD CT. Thiabendazole . Recherches sur le développement de la trichina spiralis (Ce ver devient adulte dans l'intestin du chien). Handwörterbuch der Physiologie mit Rücksicht auf physiologische Pathologie. Cited in 26 82. 1877 89. Archiv für . 75 78. MULLINS JF. 75 77. 1822. Landmarks of Parasitology. Annals of Tropical Medicine and Parasitology 54: 250-251. Berliner klinische Wochenschrift 2: 503-507. RUPRECHT B. very similar to 74. Longmans. 1859 103. Experimental Parasitology 7: 108-123. Journal of the American Medical Association 67: 579-580. 1850 100. Effect of refrigeration upon larvae of Trichinella spiralis. The production. Helminthologische Notizen. RAILLET A. Comptes Rendus Hebdomadaire des Séances de l'Académie des Sciences 49: 660-662. 1952 91. 1911 98. TWO FORMER PRESIDENTS OF THE ABERNETHIAN SOCIETY. STONE OJ. Description of a microscopic entozoon infesting the muscles of the human body. A study of an epidemic of 14 cases of trichinosis with cures by serum therapy. TIEDEMANN F. Froriep's Notizen aus dem Gebiete der Natur und Heilkunde. Partly translated in 31 99. Quelques rectification à la nomenclature des parasites. RANSOM B H. 1844 96. VIRCHOW R. Description of a microscopic entozoon infesting the muscles of the human body. OWEN R. Cortisone treatment of trichinosis. London Medical Gazette 17: 472-478. Proceedings of the Zoological Society of London. Futterungverswuch mit Trichina spiralis. OWEN R. VIRCHOW R. 1916 88. 1938 92. PAGET J. 1958 90. American Journal of Hygiene 28: 85-103. Transactions of the Zoological Society 1: 315-324. Die Serodiagnostik der Trichinosis. PAGET J. OWEN R. 1866 102. In. 1835. Experimental studies on the course of trichina infection in guinea pigs. Trichinosis. II. p 64. Green and Co. SALZER BF. KERSHAW WE. In. 1889 101. I. Cited in 76 93. Receuil de Médicine Véterinaire 3: 157-161. Demonstration of the life cycle and pathogenicity of the spiral threadworm. The discovery of Trichina spiralis. Abstracted in British Medical Journal ii: 492-493. 1901 85. R Wagner (Editor). American Journal of Medical Science 223: 16-19. 1896 87. Journal of the American Medical Association 187: 536-538. Lancet ii: 869. 1835. part 3. Lancet i: 934. 1835. Journal of Agricultural Research 5: 819-854. Report of a case. Eine Besuch in Hedersleben. 1877. VIRCHOW R. OWEN R. Münchener medizinische Wochenschrift 58: 672-674. Lancet i: 45-46. Lancet i: 269. ROSEN E. 1866 81. Lancet ii: 989. 1964 97. with an account of the productiveness of the female trichina. Cited in 56 83. PHILLIPSON RF. Identical with 76. PAGET J. 3.probable cure for trichinosis. Description of a microscopic entozoon infesting the muscles of the human body. 2: 641-692. Archiv für Heilkunde 18: 241-250. REINHARD EG. ROTH H.. 1916 95. PAGET J. 1859 104. The minimum dose of trichina larvae required to produce infestation of the muscles. 77 76. London. 1960 86. On the discovery of Trichina. REINHARD. Statistiche Rückblicke auf die Trichinen-Epidemien im Königreich Sachsen. OWEN R. TOPHAM J. Ueber Trichina spiralis. On the discovery of Trichina. 109. 114. Abstracted in British and Foreign Medico-Chirurgical Review 26: 515-516. pp 320. The discovery of trichinae. swine. The changing status of trichinosis in the United States. Public Health Reports 83: 957-966.Trichinosis 595 105. British Medical Journal i: 190. Cited in 59. Translated in 56 ZENKER FA. Trichinosis. 1862 ZIMMERMANN WJ. Ueber die Trichinen-krankheit des Menschen. KAGAN IG. 112. WALDECK. Cited in 78 ZEDER JG. Siegfried Lebrecht Crusius. 1865 WILKES S. Archiv für pathologische Anatomie und Physiologie und für klinische Medicin (Virchow) 32: 332-371. 113. 1830 ZENKER FA. pathologische Anatomie und Physiologie und für klinische Medicin (Virchow) 18: 330-345. Erster Nachtrag zur Naturgeschichte der Eingeweidewürmer von JAE Goeze mit Zusätzen und Anmerkungen herausgegeben von J G H Zeder. Deutsche Archiv für klinische Medizin 1: 90-124. 1965 ZIMMERMANN WJ. 1866 WOOD H. 110. Abstracted in British Medical Journal ii: 563-564. Abstracted in British Medical Journal ii: 402-403. 111. 106. 108. 1835 WORMALD T. 1860. Lancet i: 269-270. STEELE JH. Note sur le Trichina spiralis. 1860 VIRCHOW R. 1860. BRANDLEY PJ. Archiv für pathologische Anatomie und Physiologie und für klinische Medicin (Virchow) 18: 561-572. Observations on the Trichina spiralis. The current status of trichiniasis in U. London Medical Gazette 16: 190-191. 1968 . 1866 ZENKER. Résultat de ses nouvelles expériences.S. 1860 VIRCHOW R. Leipzig. 1860. Beiträge zur Lehre von der Trichinenkrankheit. Comptes Rendus Hebdomadaires des Séances de l'Académie des Sciences 51: 13-16. Public Health Reports 80: 1061-1066. 107. 115. with high mortality. demonstrated that muscle larvae were located intracellularly. and connected acquisition of infection with consumption of uncooked trichinous pork 1863 First major epidemic. Landmarks in trichinosis ___________________________________________________________________ 1835 1845 1846 1851 1857 1859 Paget discovered larvae in the muscles of a human and Owen reported the fact Herbst found larvae in the muscles of a cat but did not report the observation Leidy observed larvae in pork Herbst infected dogs by feeding them infected badger flesh Leuckart observed that cysts hatched larvae in the small intestine of mice Virchow found adult worms in the small intestine of a dog fed with trichinous meat 1860 Leuckart confirmed Virchow's discovery and found newborn larvae 1860 Zenker proved that T. found adult worms in the small intestine of a human.1. Germany 1865 Another major outbreak of trichinosis in Hedersleben.596 A History of Human Helminthology Table 22. of trichinosis recognized in Hettstadt. spiralis may cause a severe illness in humans. Germany in which 102 persons died 1909 Herrick and Janeway found larvae in the blood 1911 Ströbel described a complement fixation test 1963 Treatment with thiabendazole suggested ___________________________________________________________________ . Brugia malayi: Filaria malayi. 4-10 cm long. Demarquay again inserted a trocar. presented to a hospital in Paris with a left-sid ed scrotal tumour. microfilaria malayi iii. they develop over two weeks into infective larvae which pass to the proboscis and infect the host at the next blood meal. an 18 year old man. Infective larvae migrate to the lymphatic system and mature over the next 12 months or so Definitive host: i. Anopheles. elephantiasis Diagnosis: demonstration of microfilariae in the peripheral blood Treatment: diethylcarbamazine DISCOVERY OF THE MICROFILARIA In July 1862. bluish-white fluid. Wuchereria: tropics and subtropics ii. aspirated some 100 ml of thick. Cuba. timori: humans ii. acute inflammatory filariasis: lymphangitis. When microfilariae are ingested by appropriate mosquitoes of the genera Aedes. the patient returned with a similar problem on the other side of the scrotum. Wuchereria. timori: Timor microfilaria Distribution: i. Wuchereria malayi.Chapter 23 Wuchereria bancrofti. a phenomenon which is known as periodicity. originally from Havana. hydrocele. they usually appear in the bloodstream only at a defined time in each 24 hours. dwell in lymph nodes and adjacent lymphatic vessels. Filaria sanguinis hominis. chronic obstructive filariasis: lymphoedema. Jean-Nicolas Demarquay and whitish-yellow fluid similar to milk was aspirated. ascertained that the testi s was normal and demonstrated that the fluid had been located in the tunic a 597 . In August of the following year. Microfilariae are produced and released into the bloodstream. A trocar was inserted by the surgeon. Wuchereria pacifica ii. monkeys Major clinical features: i. periodic B. Culex and Mansonia. Brugia: southeast Asia Life cycle: The thread-like. malayi: humans. and B. malayi. B. subperiodic B. Filaria nocturna. epididymitis ii. FILARIASIS Brugia species and SYNOPSIS Common name: filaria causing elephantiasis Major synonyms: i. adult worms. Wuchereria bancrofti: Filaria Bancrofti. Nevertheless. it seemed likely that they were nematodes. as we think. The discovery of these worms by Demarquay and his team heralded little interest and three years were to pass before they were seen again. 239 Suspecting that these may have been a contaminant. this time in the urine. h e remarked that from a consideration of the drawings that had been made of the worms and from the description of a ctive movements. it relates a new fact. larvae of a nematode. 73 Samples of the fluid were sent to CJ Davaine for an expert opinion. In addition to the fat globules. Brazil. subsequent observations will not fail to provide all its scientific value. Wucherer attached n o great importance to this discovery. He added that the only larva l nematodes which had been observed th us far in humans were those of Trichina (= Trichinella) spiralis and Filaria (= Dracunculus) medinensis. The hydrocele fluid was examined microscopically by one of th e house surgeons.598 A History of Human Helminthology vaginalis. or more probably in view of the absence of visible organ s within the parasite. Two years earlier. Wucherer inspected a clot from some milky urine obtained from a femal e patient who was under the care of Dr Silva Lima in the Misericordia Hospital. but with a flash of insight suggested that the whole phenomenon may be related to the patient having lived in Cuba. In the blunt end a small point was visible which could not be identified as an opening. pus cells an d filaments of fibrin.73 He was also perplexed about the means by which the worms had entered the body. however. by Otto Wucherer who was completely unaware of the French discovery. since he had examined the urine of haematuric patients many times an d never found anything similar on previous occasions. Demarquay was disappointed by Davaine's failure to confirm their observations. he found many specimens of a parasite: Attention was drawn above all to a little elongated and cylindrical creature. H e devoted half an hour to searching vainly for the parasites. this fact would thus remain useless. Nevertheless. Wucherer had been stimulated by a letter from Griesinger in Germany to examine th e urine of patients with haematuria in order to see if he could find any evidence of Schistosoma haematobium infection in South America. he asked the woman t o void again into a clean container and onc e more found the helminths. he agai n . The body was transparent and seemed to contain a granular mass. it was not possible to distinguish its internal structure. but remarked sagely: If we were mistaken. Dr Lemoine. but if. especially its terminal extremity. On 4 August 1866. they were found. He looked at specimens from a number of such patients but without success. The anterior four fifths of the body had almost a uniform diameter: the posterior fifth became thinner and thinner and terminated in a fine point. This worm had extremely rapid movement of coiling and uncoiling in its different parts. Using the microscope he saw: some threadlike worms which were very thin at one end and blunt at the other. The worm was completely transparent and did not show anything which resembled the digestive system or the genital system. however. On 9 October 1866. In 1866 in Bahia. wavy motions. Germany.197 Meanwhile. 60 or 70 times.195 This was demolished summarily and in caustic fashion by a correspondent: The 'active linear vibrios' common in decomposing fluids. In March 1870. Lewis. indeed. nothing to do with these nematoid filariae. then expressed the same view about the worms found in Cobbold's patient 67. Even more remarkable was the letter by WO Priestly written to the British Medical Journal : As long ago as 1857. Subsequently. the worms found by the latter also being described by Corre 63. of course. in their historical reviews in 1878 of the discovery of this parasite were ignorant o f . They had the diameter of a white blood corpuscle and their length exceeded that of the latter. As with many other important discoveries in medical helminthology.have. but the latter dismissed them as being of no importance. Wuchere r wondered whether they came from the vagina. they were not accepted by Cobbold 60. when he also asserted that the worms found in the urine of a patient in 1868 by Salisbury in the United States 207. Lewis found delicat e filaments which he at first thought were fungi. I described a case of chylous urine. apparentl y unaware of Wucherer's discovery. but of classes. Despite these cogent arguments. unless.. not chyluria. Lewis's co-investigator. but this idea was negated when some time later he found the same parasites in the chylous urine of a man: They were alive and were making very brisk. When he examined the urine. According to Manson-Bahr 173. were in reality filariae 54. in which the milk-like fluid passed from the bladder was found on microscopical examination to contain innumerable linear vibrios. Two authorities. disposed of this latter instance by showing that the patient was a 55 year ol d rheumatic woman suffering from cystinuria.. fo und the worms in the chylous urine of a 25 year old East Indian. On continued observatio n though. there was the odd pretender to the throne. Lewis found the same worms in somewhere between 15 and 20 patients 132. Wucherer's observations were confirmed several years later by Timoth y Lewis in India and by Jules Crevaux of the French Navy 65. we adopt very advanced views on transmutation not of species. the original discovery by Demarquay and his colleague s remained unappreciated. Cobbold did not publish news of this observation until 1872. considering the parasites to be members of the family Strongylidae. and that the parasites were almost certainly those of Enterobius vermicularis . Cobbold and da Silva Lima. Leuckart in Leipzig.239 Wucherer could find no reference to similar parasites in the works of Küchenmeister. Wucherer sent specimens of the worm preserved in glycerine to the renowned parasitologist.Filariasis 599 found similar worms in the urine of another lady with haematuria. Cunningham . and which that observer had called Trichina cystica. he saw that they coiled and uncoiled and realized that they wer e worms131. Cobbold or Davaine. Spencer Co bbold claimed that in July 1870 he had found similar worms in the urine of a South African girl wit h schistosomiasis. or filariae which moved in every direction across the microscopic field. but he did not report them as a new species .. he noted that this was not a common occurrence and that it was often necessary to examine several of the slides before the parasite could be found. the numbers of worms in the blood diminished markedly (blood samples were presumably taken during the day): the numbers obtainable by pricking the fingers or toes certainly decreased and eventually.the firs t investigator who proclaimed the existence of a new human entozoan. demonstrating its embryos in chylous urine" 220. In view of the subsequent discovery of the nocturnal periodicity.e.000 of th e parasites. and distributing a drop of blood over several slides. but found to his intense disappointment that the patient ha d discharged himself one hour earlier. however. each slide taking about 15 minutes to complete. Lanceraux i n Guadeloupe. Lewis went back to the Hospital to review the patient' s clinical history. Lewis kept her under observation for about two months. Lewis agai n found worms in the urine of a woman with haematochyluria. i. well-developed Haematozoa are invariably obtained. out of half a dozen or more slides.132 Shortly afterwards. on a few occasions several slides were examined without any being found. he made a much more important further observation.. Douglas Cunningham. Perhaps burned by his previous experience. for "O n pricking her finger with a needle. L ewis visited her that same evening.the number infesting his whole body may be imagined. Two years after Lewis found organisms in chylous urine. Nevertheless. In July 1872. On th e following morning. I found that Filariae were present in it also" 132. All attempts to find him. Several days later.. while examining the blood of a patient with diarrhoea who was under the care of Dr Chuckerbutty in the Medical College Hospital in Calcutta. on one occasion I observed as many as 12 of these creatures on a single slide. It was not until 1888 that Demarquay's contribution became widely known when his countryman.. the transient surge o f microfilariae into the bloodstream at night after a complete or almost complete absence during the day. He showed them to his colleague. proved fruitless.. pointed out with som e acerbity that not Wucherer but Demarquay had first found the parasite 125. Lewis was amazed to find: that no matter at what portion of his body the circulation is tapped with the point of a needle. Lewis "observed nine minute Nematoid worms in a state of great activity. and found that although there was littl e change in her clinical condition and there was only a slight reduction in worms in the urine. who co ncurred with Lewis's opinion that they were the same as those that had been seen earlier in chylous urine. Lewis calculated that one patient was host to some 140. even invoking the aid of the police. 132 Indeed. not more than one or two Haematozoa could be detected. Lewis encountered a third patient.600 A History of Human Helminthology Demarquay's contribution. a 22 year old Eas t Indian who spent most of his time employed as a cook on a lighter lying in the mouth of the River Hooghly.. numerous active. this was undoubtedly a fortuitous event. with the former writing "the larval forms firs t described by Wucherer" 60 and the latter remarking "Dr Wucherer.. on a single slide" 132. When Lewis went to the Government Printing Es tablishment to examine the . The name "filaria" was a modern Latin derivative. fish. which he termed haematozoa. "filarium" indicating "ball o f thread". though it is perhaps still more astonishing that they should produce such a comparatively trivial amount of inconvenience. who considers it to be some kind of Filaria. rats and dogs. Lewis's long paper was published as an appendix to the Annual Report for 1871 of the Sanitary Commissioner 132 and was abstracted later in The Lancet 7. meaning "thread". although schistosomes had been found in the portal vein and its tributaries by Bilharz in 1851 and it was suspected that Trichinella spiralis larvae might migrate to th e muscles through the bloodstream. and became the subject of a multitude of paper s and letters.5 The name. Enquiry revealed that he was healthy and examination of his blood disclosed the presence of sparse numbers of worms 132. meant that the filar ia had been found in human blood. It glided amongst the blood globules. The nematoid had the shape of an Anguillula. placing it directly under the objective glass. foun d . both in Australia. In addition. of course. but this was the first occasion on which multitudes o f worms had been found in the general circulation of humans. who stated that the helminth belonged to the genus Filaria of Müller179 and that Busk had also suggested a name for th e parasite: A specimen of the embryo of the chylous-urine worm has been submitted to Mr. when with astonishment I discovered a living organism in the midst of haematic globules. The same commentator noted that the nature of the worm had been determined by George Busk . birds. and it may not be inappropriate to christen the new entozoon 'Filaria sanguinis hominis'. The discovery by Lewis of worms in th e blood. This feature led him to surmise that the pa rasite had no means of perforating the tissues and that its normal habitat was the blood. which were tossed to and fro by lively movements. caught the imagination of the Englis h medical world in particular. withi n which the worm was capable of elongating and shortening itself.Filariasis 601 galley proof of his report on the discovery of microfilaria in the blood. Nematodes and flukes had been found in the blood of molluscs. Lewis described the morphology of the parasite and discerned the sheath. he noted a bright spot at the blunt end of the worm which was suggestive of a mouth. Rowland 206 and then Bancroft . but news of his discovery was first revealed in an annotation in The Lancet of 31 August 1972 5. Busk. of the Latin word "filum".6 Lewis's discovery was confirmed by Sonsino in Egypt on 1 February 1874 while searching for schistosomes in peripheral blood: I put a drop of blood (from the finger of the boy) under the microscope.221 22 Also in 1874. frogs. indicating that it was an extremely delicate tube closed at both ends. An editorial writer in the British Medical Journal remarked: That organisms so high in the scale as nematoids should be found to swarm as parasites in this situation is not a little surprising. he was astounded to find that the man setting up the type was none other than the first patient in whom he had found microfilaria in the urine. the blood had to be inspected for embryonic filariae. As a preliminary enquiry. under the microscope it was without doubt a worm. the following year. a specialist in urinar y diseases. My first specimen I got on December 21st 1876 in a lymphatic abscess of the arm. This was the second case in which the blood contained the parasite in question. On March 21. in an elderly patient with a trochar and cannula. Cobbold found four female worms and multitudes of ova and larvae which he described in some detail in a paper published on 6 October . I tapped a hydrocele.a threadlike body came into view. the latter's observation being announced by Cobbold 56 who observed microfilariae in blood sent to him in capillary tubes vi a Bancroft's old teacher.. Embryos in abundance were found in the hydrocele fluid and in the patient's blood.602 A History of Human Helminthology microfilariae in blood. On examining the matter.. Cobbold named the worm Filaria Bancrofti in honour of Bancroft: "Such Sir. he wrote to Bancroft suggesting that he look for the adult worms whic h Cobbold felt must be present in the human body.. is Dr Bancroft's account of his 'finds'. I collected the matter as usual in a small vessel. Subsequently. and embryos were seen coming out of its body. and am glad to tell you that I have now obtained five specimens of the worm. Bancroft sent the adult filariae to Cobbold who received them on 28 August 1877. In his letter. Cobbold was strengthened in this belief when he saw an empty egg shell which he interpreted as being the remnant of the egg from which the filarial larva had come (it is impossible in retrospect to say what in fact this was). On withdrawing. Dr W Roberts of Manchester.21 Meanwhile. By two loops from the centre of its body it emits the filariae described by Carter in immense numbers. and from the brief description furnished I propose to call the adult nematode Filaria Bancrofti. and is from three to four inches long. DISCOVERY OF THE ADULT WORM WUCHERERIA BANCROFTI After Cobbold received a specimen of blood from Joseph Bancroft in Australia. a lash of hairlike bodies was caught in the eyes of the instrument. Four others I obtained alive from a hydrocele. 23 Cobbold sent Bancroft's letter together with some explanatory notes to The Lancet wherein it was published on 14 July 1877. he found four more specimens and wrote to Cobbold on 20 April 1877 of his discovery: I have laboured very hard to find the parental form of the parasite. Bancroft took up Cobbold's suggestion and on 21 December 1876 found an adult worm.57 Bancroft later described the circumstances surrounding his discovery i n somewhat more detail: I opened an abscess in the arm of a youth employed as a butcher. The worm is about the thickness of a human hair. At once suspecting their real nature. I put them in the hydrocele fluid when they began to move around with great activity. then by Manson in Amoy. He published a brief record of the discovery in the British Medical Journal in 1888 37. Cobbold therefore attached an appendix to his second paper on the subject of the adult worm: Since the above was written.. Brazil in 1886 had found two filaria l ... even when the embryo acquires worm-like appearances.. he persisted in an error which he had made previously in believing that the microfilarial sheath was a commencing ecdysis. were found to be specimens of two mature filariae..Filaria sanguinis hominis . however. The other helminth was damaged and Lewis thought it may have been a fragment of a male worm. China in 1881 161. 134 One parasite was clearly a female worm. Dr Lewis has himself furnished additional means of identification. appear probable that. Timoth y Lewis also described his find ing of two adult worms after spending eight hours searching through scrotal tissue removed at operation from a young man i n Calcutta by Dr Gayer: At last.It would.. Despite being aware of Cobbold's designation of a similar worm as Filaria Bancrofti. Lewis recognized that the egg "shell" became the sheath of the microfilaria: It is. however. but th e important caudal part was unfortuna tely missing. Brigade-Surgeon Sibthorpe at the Madras General Hospital.on the grounds that a new name would only lead t o confusion. Lewis retained the name originally applied to the embryo . These on being transferred for examination under a higher power. Bourne found that one of th e parasites was a male filaria.. One of these contained ova. Bancrofti are clearly the same species. professor of biology in the Presidency College.difficult to state whether they are to be considered as freed embryoes or not.Filariasis 603 187758. India. In the previous issue (29 September 1877) of the same journal. Bourne himself als o published an extended. Although Bourne and Sibthorpe claimed that this was the first time the complete mal e worm was described. my eye was arrested by white thread-like objects in a state of great activity. whilst teasing a blood clot under a dissecting microscope.58 Subsequently. then a more detailed descriptio n incorporating Bourne's written comments was published by Sibthorpe in th e same journal in the following year 217.. Saboia in Bahia. foun d worms in an amputated lymph scrotum and sent them off to Alfred Bourne .. as the egg-'shell' has become so extremely attenuated and translucent as can only with difficulty be distinguished. with embryoes identical in appearance with the free embryoes in the blood.If Lewis's trinomial name for the adult worm be adopted in place of Filaria Bancrofti. 134 Moreover. illustrated version in an Indian journal 38. Meanwhile. the envelope is usually not lost in this species as long as it continues in the blood. It was not until 1888 that a complete specimen of a male worm was found. His mature Filaria sanguinis hominis and my F. In this paper. female adult worms we re found in patients in South America by da Silva Araujo on 16 October 1877 218 and by dos Santos on 12 November 1877210. Lewis emphasized the diagnostic impo rtance of this feature in differentiating these microfilariae from those found in the blood of dogs. In contrast to Cobbold. I have personally no objection. Manson called it Filaria nocturna in order to distinguish it from the microfilaria which had a diurna l periodicity (which turned out to be Loa loa)165. It is possible they were immature Dirofilaria immitis. including figures. that had been sent to him by Lichtenstein. SL Brug reported that the microfilaria e which were present in the blood sa mples. In contrast to the latter worm. but were also non-periodic. da Silva Araujo called the worm which he found in a lymph scrotum "Wuchereria Filaria"218. Although it is generally accepted that Brug first proposed the name Filaria malayi. but whether he meant to use "Wuchereria" as a true generic name is doubtful. Daniels considered the parasites distinct . On the other hand. were not infective to a variety of culicine mosquitoes 137. malayi. It was not possible to obtain adult worms because o f opposition to autopsy examination by the local Muslim population. more likely he was refer ring to "Wucherer's filaria". the worm henceforth being known as Wuchereria bancrofti 216.604 A History of Human Helminthology parasites in the right side of the heart of a boy who had died from a n undisclosed illness. there were t wo or three nuclei in the tail and the anal pore was further forward. giving them quite different dimensions 71. Parenthetically. bancrofti. although de Magalhães 150 sent a copy of this account. t o Joseph Bancroft in Brisbane who accepted them as a female and male Filaria bancrofti. In 1921. DIFFERENTIATION OF BRUGIA SPECIES In 1927. In any event. and Manson-Bahr proposed the name Wucheria pacifica for the aperiodic form of the parasite 172. Sasa211 believes that the credit should be given to Lichtenstein who not only found the microfilariae. they named this parasite Filaria philippinensis 16. it must also be said that in 190 5 Ashburn and Craig described a ca se of filariasis in the Philippines in which the microfilariae were not only different morphologically from those of W. a belief which is supported by Manson-Bahr's statement that he had examined the photo - . It is quite possible that these worms were B. but also wrote that the filaria discovered in Bireuën is hencefort h named Filaria malayi 137. Several other names apart from Filaria sanguinis hominis and Filaria bancrofti have been used to describe these parasites. In the following paper in the same journal. noting that this was the first time in which the male parasite had been described 21. bancrofti. but Brug proposed the name Filaria malayi for the parasite 41. were different morphologically from those of W. Seurat formally separated this pa rasite from the other filarial parasites on zoological grounds and adopted da Silva Araujo's Wuchereria as the generic name. da Silva Araujo called the same worm Filaria wuchereri 219. Lichtenstein in Bireu ën in the Dutch East Indies (Indonesia) indicated that filariasis was common in the area but that the microfilariae. although of a periodic type. In 1877. described the essential morphological differences and reported the unexpected insusceptibility of Culex fatigans (= quinquefasciatus). two years later. this worm was subsequently renamed Brugia pahangi by Buckley46. microfilariae morphologically indistinguishable fro m Brug's worm were recognized increasingly in parts of Southeast Asia an d southern India. then the correct name for B. pahangi of cats. Brugia. patei of dogs and cats in East Africa 45. then a more complete description of what was presumed to be W. infected Mongolian gerbils with the infective larvae. Nevertheless. On the basis of a study of these specimens. so they included them in the genus Wuchereria. so they designated the worms Wuchereria malayi 198. That the parasite was capable of infecting humans was proven by Edeson and his colleagues in 1960: two volunteers were infected . If this is true. Rao and Maplestone reported the recovery of the parent worms of microfilaria malayi from a patient with a lymphatic cyst on the forearm. then on e developed microfilaraemia 84 days after inoculation 80. Their views were confirmed soon afterwards by Bonne and hi s colleagues35. dogs and monkeys in Malaysia.46. beginning with Korke in India 123. In 1971. Be that as it may. In the following year. the first being reported b y Rosenblatt and colleagues 203. One was microfilaria bancrofti and the other resembled microfilaria malayi. Poynton and Hodgkin indicated that they had found similar microfilariae in a Kr a monkey (Macacus irus)194. Buckley erected a new genus. then recovered and described the adult worms which they designate d Brugia timori 190. As already mentioned. bancrofti. In 1939. in honour of Brug.Filariasis 605 micrographs in Ashburn and Craig's paper and concluded that it was possible that they had described microfilaria malayi 172. B. Buckley and Edeson described Wuchereria pahangi. In the early 1960's. both experienced episodes of lymphangitis and lymphadenitis. they believed that the morphological appearance of the microfilariae and their development in different species o f mosquitoes justified specific status. malayi and two closely related worms. HL David observed that two kinds of microfilariae were present in the blood of military recruits in what was then Portuguese Timor . In 1965. Partono and his colleagues fed Aedes togoi on people with this microfilaraemia in a village on Flores. Six human cases of infection in the United States with this or a closely related parasite have been published. a parasite of the raccoon15. Eventually. to house B. malayi would be Brugia philippinensis. but those authors detected some slightly more substantial differences in the male worms. . The resemblance betwee n these microfilariae and those of Loa loa led to some speculation that the parent worm of these microfilariae may resemble the latter worm. David and Edeson published their finding that this latter worm was a distinct microfilaria which they named Timor microfilaria 72. Indonesia. a parasite of cats47. Ash and Little described Brugia beaveri. and B. The female specimens were quit e indistinguishable from those of W. In 1955. malayi was provided by Buckley and Edeson with material recovered from a monkey47. then examine d their abdominal contents at daily intervals. Cobbold. otherwise they would kill the host and thus prevent transmission to another host. In an almost banal fashion. mosquitoes and sandflies. it turned out to be true in this particular case. and he soon found microfilariae in the blood of a number of patients. bedbugs. and being otherwise suited for an independent existence. Manson had practised for eight or nine years in the Orient and had seen many cases of elephantiasis and lymph scrotum. some microfilariae that had been discovered in the blood by Lewi s were exhibited at a meeting of the Pat hological Society of London. they could not believe that tens of thousands of these worms could get in from the external environment. 1876 saw him back in Amoy. In blissful ignorance of the almos t world-wide dissemination of mosquitoes. All of these ideas remained mere speculation. however. 156 . possessing an alimentary canal. Manson dedu ced that the most likely means of exit was via a blood-sucking insect. This was clearl y untenable as it would lead to extermination of the parasite. He postulated that the larvae must escape from the host. Bastian and Harley objected to any idea that man could be an intermediate host. basing his argument upon the recent demonstration of the role of crustaceans in the transmission o f Dracunculus medinensis. and that the haematozoon which entered the mosquito a simple. after passing through a series of hightly interesting metamorphoses. lice. In order to test this hypothesis. he selected these insects as th e probable candidates because he thought their geographical distributio n coincided most closely with t hat of the parasite. Since a person might harbour hundreds of thousands of larvae. Manson wrote: I found that my idea was correct. or in some intermediate host where they matured befor e ingestion by another person.606 A History of Human Helminthology ELUCIDATION OF THE LIFE CYCLE: DISCOVERY OF TH E MOSQUITO INTERMEDIATE HOST In 1873. he acquired both a microscope an d knowledge of Lewis's discovery. extrapolated this to conclude that an intermediat e host was always required for nematodes. until Patric k Manson entered the fray. structureless animal. He was puzzled about the fate of these larvae and determined to try to ascertain their destiny. Manson thought it most unlikely that they matured withi n the human body. Cobbol d postulated that either adult worms which produced these forms were normally present but unnoticed in humans or that they we re the progeny of an adult worm which had strayed into humans from some carnivorous animal 55. China. so inferred that adult worms must live within the human body 31. When he returned to Britain on furlough in 1875. much increased in size. left it. While this would prove to be false as a general rule. who had a marked microfilaraemia. either in a free-living state. so he considered the possible roles of fleas . then develop further. Hin-Lo. he procured some mosquitoes and fed them on 10 August 1877 on the blood of his gardener. This excited considerable interest and in the ensuing discussion consideration was given to the possible life cycle of this parasite. Blood corpuscles distinct . I was gratified to find that. only four lived beyond this stage. Because of the paucity of specimens.... for he had never seen a male mosquito engorged with blood . And now I saw a curious thing. a dingy brown insect about 8 mm in size (C. He then described the changes in the appearance of the microfilariae. Perhaps an oesophagus developing. and 4.. 2. the larvae ceased their movements and entered a "sort of chrysalis condition" and became shorter and fatter s o that by the third day they resembled a sausage. remain there for several days. Manson remarked that these processes always took place within femal e mosquitoes. These were about the size and might have been embryo filariae dead. Thirty six hours after ingestion by th e mosquito. h e assumed.Several cylindrical bodies of a pale grey colour and distinct outline. No. Further. Manson had great difficulty in observing these later stages. quinquefasciatus. Double outline and transverse striation on the integument most distinct. he stated that his studies were always performed with the mor e common of the two mosquitoes prevalent in his region.5 and 1 mm in length. which hitherto had muzzled it. 1. I tore off its abdomen and succeeded in expressing the blood the stomach contained. following which. he was uncertain of the details of this stage o f metamorphosis but found that the alimentary tract became distinguished more clearly and thought that the worm may have a boring apparatus on its head. The little sac or bag enclosing filaria.. He observed the replete mosquitoes fly off to near stagnan t water. No. and in one of these he saw a gradation of forms from the passiv e chrysalis to an active larvae between 0. oral movements very apparent. anterior head loop often very distinct.169 The bare bones of his find have been recorded in his diary: Hin-lo brought me four mosquitoes which he had caught this morning in his mosquito net and which were distended with his blood. while the other species was probably Aedes aegypti).was broken through and discarded.Filariasis 607 Manson's true feelings on that day in 1877 may be guessed better from a speech which he later gave and which was reported in the Daily Telegraph: I shall not easily forget the first mosquito I dissected. Out of hundreds of mosquitoes that he watched. Placing this under the microscope. whic h occurred around the fourth to the sixth day because most of his mosquitoe s died. Different from those in man's blood in being perhaps more active. 3. the digestive juices of the mosquito seemed to have stimulated fresh activity.168 In his original paper. Blood corpuscles also digested and two bodies one of which had a distinct to and fro movement of the head half of the body and the appearance of ciliary current at the mouth. Manson surmised that the life cycle of the worm wa s . A mouth and intestinal tract then appeared and the worms grew in length.. Blood corpuscles not distinct.in both live active filariae and in one of them ten specimens. Tail not well seen. then deposit eggs. so far from killing the filaria. Manson noted that the mosquitoes took only a minute or two to become engorged with blood and seemed to have the capacity t o concentrate microfilariae fro m the bloodstream. they died. I examined them this morning. No. hardly be safe to assert positively without further experience. Manson eloquently expressed his reasons for this in his letter to Cobbold of 27 November 1877: I live in an out-of-the-world place. and then either piercing the integuments. but in a cursory way. what is more probable. it works through the alimentary canal to its final resting place. and out of the run of what is going on. or if it has been done before. escaping onto the water in which the mosquito died.. and finally the embryo filariae we meet within the blood are discharged. He sent copies to Lewis in India.. its development is perfected.24 Nevertheless. Cobbold was fulsome in his praise of Manson: Whether or not this conception of the possible host-relationship. They appear to die in water. Arrived there. On receipt of this. and forwarded him a treatise on cockroaches in the hope that that would do instead. being swallowed. he wrote to the British Museum and the relevant authority replied regretfully that no such work existed. Indeed. He wrot e immediately to The Lancet (12 January 1878) conveying news of the observation and also remarking that Joseph Bancroft in a letter to Cobbold in April the previous year had written: I have wondered if mosquitoes could suck the haemotozoa and convey them to water. I had frequently examined these insects. Desperately searching for inf ormation. I will examine some mosquitoes that have bitten a patient to see if they suck up filariae.167 Lewis replied to him from Calcutta on 14 January 1878: Allow me to congratulate you on your extremely interesting observation regarding the embryonic nematode in the mosquito. until I received your note. Whether they are actually identical or not it would. Manson's paper was first published in the Medical Reports of the Chin a Imperial Maritime Customs 156.608 A History of Human Helminthology completed in the following manner: There can be little doubt as to the subsequent history of the Filaria. but certain it is that what Bancroft surmised Dr Manson has demonstrated to be a fact. Manson was positively misled about these aspects by the one book that h e eventually found on the subject.I consider Manson's discovery almost of a par with the separate announcements of Lewis and Bancroft. so I do not know very well the value of my work. I repeated such examinations and found that several of the mosquitoes which were examined contained little nematodes resembling most perfectly those found in human blood. Filaria sanguinis hominis. perhaps. 59 . 136 Cobbold received Manson's communication on 4 January 1878. Cobbold in England and Leuckart in Germany. He was wrong about their geographical distribution and their life span and was not aware that they could bite more than once. as between man and mosquito. fecundation is effected. it is through the medium of this fluid brought into contact with the tissues of man. or that.there had been littl e incentive to interest anyone in mosquitoes prior to his epochal discovery . or. but had not observed any parasites in them at all resembling the embryo.. away from libraries.156 Manson knew little about the natural history of mosquitoes. But he was not alone . primarily originated with Bancroft or some other observer. or better. I cannot stop to inquire. Manson-Bahr and Alcock. it cannot be said that even these later observations are sufficiently conclusive to warrant a positive statement being made at present.135 In the middle of 1878. According to Cilento53. Leuckart discourses . da Silva Araujo in Brazil also confirmed Manson' s observations when he found W. Bancroft in April 1877. Lewis removed the alimentary canal an d examined it separately. Manson's biographers. to the inference that the mosquito is the particular intermediary host of nematoid haematozoa. This seems a fair comment. however. assuming that of the various parasitic forms which have been seen several are actually transitional stages in the development of one and the same entozoon. for in the 1886 edition of his Parasites of Man. At first Lewi s was in considerable doubt. pass out. and every attempt hitherto made by myself to obtain a more advance condition has been unsuccessful. have remarked that Leuckart was initially an unbeliever and seems never to have given Manson's discovery anything but a grudging and disparaging a cknowledgement 175. . The publication 157 which followed Cobbold's verbal report was the same as the parasitological com ponent of Manson's Custom's Report 156 except that the illustrations of th e various forms of developing larvae were omitted. he found that the same worms "actually perforate the walls of th e insect's stomach. for in contrast to Manson who had squashed th e whole of the posterior portion of the mosquito and assumed that the variou s events took place within the gut. bancrofti larvae in mosquitoes fed on the blood of a French priest who had a microfilaraemia 219. fed some Aedes vigilax. and then undergo developmental stages in it s thoracic and abdominal tissues" 135. and Lewis did not altogether dismiss them. however. Manson was lucky while Bancroft was unlucky. Cobbold communicated formally Manson's account i n which the latter characterized the mosquito as a "nurse" of the worm. Manson chanced upon an efficien t vector of the parasite (C. This article was stimulated by the publication by Lewis in Calcutta of the results of his attempts to repeat Manson's experiments. Further observation. It was not until June of that year. on an infected person bu t was discouraged by the negative results. however. for though. Leuckart appeared to pay no attention at all to them. and saw fe w parasites after the third day. a poor vector as it turned out. quinquefasciatus) for use in his studies. to th e Linnean Society in London. that the British Medical Journal was constrained to publish an editorial entitled "Is the mosquito the intermediary host of the Filaria sanguinis hominis?"8. In the discussion that followed. however. it is to be noted that even the most advanced stage hitherto observed is still a very immature one . Manson's opinions were accepted by a number of eminent authorities. In March 1878. may overcome or explain this want of success. before Manson had begun his studies. Subsequently. Lewis's conclusion was very cautious . While Cobbold accepted Manson's views unreservedly. although it left open the possibility of mosquitoes being the intermediate host of filariae: With regard.Filariasis 609 Adequate recognition has not been given t o Bancroft in this regard. an anonymous reviewer (?Cobbold) in the Veterinarian suggested the true mechanism when he wrote that the infective larva (which he called th e "parent") is "deposited by the mosquito in the act of biting" 10. Sonsino in Egypt also confirmed Manson's observations when he found a n infective larva in a C. ciliaris = C. In the event.000 mosquitoes. The most advanced larvae were recovered from two mosquitoes 6.5 mm long. discovered that mosquitoes could be bred and kept alive in confinement for up to two months when fed upon ripe bananas 26. Finally. made no mentio n whatever of his studies with mosquitoes: The haematozoa. having secured a position elsewhere as a domesti c servant. quinquefasciatus permitted complete development and one of the other three allowed development only up to a certain point 164. Carlos Finlay in Cuba had in fact shown in 1881 that mosquitoes could be kept alive for weeks on blood o r sugar86 but this information was lost sight of and never acted upon. In the same year. he found that his patient had left town. after a longer or shorter sojourn in the blood-vessels. Manson repeated and amplified his observations in 1883 and communicated the results through Cobbold to the Linnean Society in London in 1884. only the form now known as C. As so frequentl y happens in science. Ronal d Ross also re-discovered this phenomenon in his experiments on the malaria l parasites of birds. Although Manson suggested the possibility of skin penetration by infective larvae through the use of the "boring apparatus". and continue their life-history under other conditions. Fortunately. Indeed. or the reservation with which it was accepted. It was not until 1899 that Thomas Bancroft. the course of events did not run smoothly. these were infective larvae 1. Manson illustrated th e metamorphoses in great detail and anticipated the fact that the larval filaria e underwent at least two ecdyses in the mosquito. another anonymous reviewe r five years later stated that the larvae probably penetrated the skin of bathers 11. when he kept them alive by re-feeding them on blood 205. in Queensland. th e gardener. he preferred the alternativ e option of ingestion of larvae liberated f rom dead mosquitoes in water.610 A History of Human Helminthology at some length on the discovery of microfilariae in the urine (mostly quotin g Lewis) as a means of escape for microfilariae and although he alluded t o Manson's discovery of the periodicity of microfilariae. he was able to induce her with the aid of a seven pound grant from the Queensland B ranch of the British Medical Association to return .130 Stung by such indifference to his discovery. then. Bancroft used these laboratory-reared and maintained mosquitoes ( C. he pointed out that of the four species which he now recognized in Amoy.5 days after they had fed on Hin-lo. This suggestion was not taken up with any enthusiasm. but Bancroft was apparently unaware of these contributions. Thomas Bancroft. quinquefasciatus) and fed them upon a 15 year old girl. would appear to leave the body of their host in some way or other. Joseph's son. He dissected over 1. for whe n Bancroft was ready to embark upon the scheduled experiments. In March 1888. put the piece s into place so that the puzzle cou ld be solved. pipiens captured in the house of a filarious woman 222. Thomas Bancroft determined the underlying conditions necessary for carrying out the experiment. In contrast to Manson who ha d found filariae in various stages of development within the one mosquito . then no further changes occurred for the next six weeks. he would undoubtedly have followed the whole proces s through to its logical conclusion. awaiting an opportunity to enter the human tissues when the mosquito next feeds on man. In this way. With masterly understatement Low then wrote: It is difficult to avoid the deduction that the parasites so situated are there normally. prophesied the outcome. the head being invariably in advance" 140. for Manson had caught wild mosquitoes. In that letter he noted that infective larvae were not killed by bein g placed in water. If he had had the appropriate technica l resources at hand. Bancroft first published notification of his findings in the Australasian Medical Gazette in 189925. pushing forward between the labium and hypopharynx: "Here I have frequently found them stretching along almost the entire length of th e proboscis. In view of these findings. Bancroft observed that all of his larvae were at the same stage of development. Low published some magnificent figures of larval filariae in the abdomen and thorax then illustrated their passage past the salivary glands into th e proboscis. Bancroft suggested that the rare.140 Many commentators have given Low the credit for discovering the tru e manner of transmission of filariasis from mosquito to man. however. Bancroft modified his earlier statement and reported that the larvae died three to four hours after immersion in water. 16 days were required in warm temperatures for development to be completed.Filariasis 611 and live with her parents for three months. and he wrote in an addendum dated 1 June 1899: It has occurred to me that young filariae may gain entrance to the human host whilst mosquitoes bearing them are in the act of biting. The entrance of warm blood into the mosquito may excite the young filariae in consequence of which they pierce the oesophagus and pass down the proboscis into the human skin. h e was but the technician who made the final but inevitable observation. Moreover. Nevertheless. Much credit must also be given to Captain SP James of the Indian Medical . and suggested that infection for the human host via thi s medium should be confirmed experimentally on life-sentenced prisoners and offering them a free pardon as a reward. and actually prepared the mosquitoe s from which the sections were made. In June 1900. Thes e mosquitoes were fixed in celloidin and histological sections were cut. This led him to cast doubts of the water-transmission theory. injury from human digestive agents would be avoided. fully-developed larvae which Manson had seen seven days or so after feeding must have been derived from an earlier blood meal.26 Bancroft then sent some filariated mosquitoes that he had prepared t o Manson in London who in turn passed them on to George Low who was working under his direction at the London School of Tropical Medicine. In his more detailed report published later that year. The moment Dr.. absolute honesty is the first qualification in all scientific work and the man who attempts to deceive his readers on the question of priority can hardly complain if we refuse to believe in his researches. Low's work by inventing imaginary faults in it . but is applied against the skin and encircles those parts of the proboscis which do penetrate the integument . In my humble opinion.184 claimed that the mosquito propagation of filariasis was an "Italian discovery". Low's work was published.I fear I cannot do myself the honour of including the labours of Professor Grassi in any future writings . Stimulated by Thomas Bancroft's report tha t mosquitoes could be kept alive by feeding them on bananas. Noè a 'preliminary note' in which he began by implying (but without giving details) that he himself had independently made the same discovery . stimulated by Low's report. Kennard did not believe it possible for the hypopharynx to admit so large a n organism as the infective larva. Having thus shifted the merit of the inoculation hypothesis of filariasis to his own credit. objected that the la bium is not inserted when the mosquito feeds. Shortly afterwards.612 A History of Human Helminthology Service in Travancore. Needless to say.. Professor Grassi. announced that they had confirmed the observations by finding filariae in the proboscis of Anopheles 12.the hypopharynx. so cast do ubt upon this mode of transmission 118.an artifice which he consistently adopts in regard to my own work. India. One notes at once that he adopts in his new enterprise precisely the same devices as he used previously in connexion with the mosquito theory of malaria. he permits his pupil. Kennard in British Guiana. mandibles and maxillae .204 Ross then recounted a number of other i nstances of similar chicanery by certain (but by no means all) Italian writers. Soon after publication of Low's paper. neither he nor his pupil has ever made a single new observation on filariasis. then Noè alone183. afte r noting that Low had stated that the larvae were located between the labium and hypopharynx. but only an attempt to peg out a fresh claim for priority by. showed that infective larva e migrated into the proboscis of certain anopheline mosquitoes 116. Noè to draft the entire subject into his account by saying that the 'Italian discovery now at last enables us to place the prophylaxis of filariasis upon a solid basis'. and then proceeded to deprecate Dr.a thing for which I have reasons for disbelieving. he adopted th e same technique and independently of Low.. These authors. the larvae escaped through a rupture in the bent labium 99. Dr.. but for my own part. or on behalf of. he hastily issued with Dr. a claim that was roundly cond emned by Sambon 208 and Ross204. science is too great a thing to be made a field for tricks like those of a pettifogging village attorney and we have every right to resent their introduction. Moreover.. the members of the second malaria expedition to West Africa of the Liverpool School of Tropical Medic ine.Others may do as they please. and concluded: It is a question how to deal with such efforts.. The latter (who had suffered previously at the hands of Grassi with respect t o malaria research) wrote trenchantly: the work is not a serious effort of science. Similar comments were made by Grassi and Noè who wrote that when dogs were bitten by Anopheles mosquitoes infected with Dirofilaria immitis. Thus. Manson was struck by the fact that the night worker found more parasites than did the . Dutton and Elliott in Nigeria in 1901 wh o showed that Anopheles costalis was a vector 3 and then by Bahr in Fiji wh o worked with Aedes variegatus (= pseudoscutellaris = polynesiensis)19. 23 species were said to allow partial development 81. Thomas Bancroft in 1901 used D. he exposed a thre e week old uninfected pup to 183 filariat ed mosquitoes. bancrofti 116. mosquitoe s were observed. then several years later. In 1930. James in India reported that Anopheles rossi was a vector of W. Edwards was able to list seven species in which complete development of W. The original mosquitoes which Manson had used in his experiments wer e proven more than 50 years later to be Culex quinquefasciatus (= fatigans) when some mosquitoes that he had filariated and sent to Cobbold wer e discovered in bottles at the Royal College of Surgeons in England 174. DISCOVERY OF THE MICROFILARAEMIA NOCTURNAL PERIODICITY OF During 1876 and 1877. Neverthless. there seemed little doubt that a similar mechanism was involved in human filariasis.Filariasis 613 of my own and think that science will not lose much if the papers by him and Dr. Basic knowledge of mosquito biology was poor in those early years. bancrofti microfilariae had been shown. annulatus (= Mansonia annulata)43. One of these persons worked during the day and the other laboured at night. he trained two Chinese a ssistants to make blood examinations. Further. Eventually. Brug and de Rook reported that th e newlydiscovered B. hundreds of species o f mosquitoes were known to be transmitters of this infection. Feng showed that the major vector of this parasite in Huchow. No t only were the behaviour and natural history of mosquitoes dimly understood. but many species were undiscovered or unnamed. dives) and T. although wit h varying degrees of efficiency 211. malayi completed its development in Taeniarhynchus annulipes (= Mansonia annulipes = M. immitis were recovered from the right ventricle and the pulmonary artery 28. sinensis 85. Nine months later. Noè on filariasis are similarly excluded from monographs on that subject. Manson noticed that microfilariae could not always be found in patients whom he knew from previous observations to be infected . In 1900. microfilar iae appeared in the peripheral blood. In addition. in a well-controlled experiment on 30 December 1902. 204 Meanwhile. and their ability to permit development o f microfilariae determined experimentally. then the dog was killed and 16 male and 16 female adult D. two of which bit the dog. China was Anopheles hyrcanus var. immitis as a model to show clearly that larvae escaped through the labe lla at the tip of the labium 27. In 1900. categorized. then he was followed by Annett. By 1922. When Sasa came to write his review of filariasis in 1976. 110 species of mosquitoes were known. more than ten times that number had been described 81. By 1922. Manson was very thankful for the efforts. Manson had wondered whether th e microfilariae died each day and were replaced by a new brood.. a man who had been known to have a microfilaraemi a committed suicide with prussic acid and died almost instantly at 8. The embryos are in the blood just at the time the mosquito selects for feeding. On hearing about MacKenzie's experiment . 168 Manson confirmed his observations on further patients and published th e results in the Customs Report 159. which he found had partial periodicity. immitis. from which time till the following noon their numbers gradually decrease. my work would lie entombed in the 'Customs Gazette' of little use to anyone. Following a post-mortem examination. at the suggestion of Vandyke Carter. Many years later. however. succeeded i n reversing the periodicity by persuading the patient to sleep by day and stay up at night146. 160 Cobbold's presentation of Manson's finding was greeted with astonishment by some and with downright disbelief by others. In 1879 . he gave directions for a particular patient's blood to be examine d daily and found that on some days there were abundant microfilariae whereas on others there were none or ve ry few. with one wag enquirin g "whether the filariae carried watches" 9. for he later wrote to Cobbold: I am very grateful to you for the trouble you have taken in bringing these forward and cannot but feel that unless for your kind assistance. that a few are found in . so he made a series of systematic examinations every few hours on this patient and in a number of others. then the scoffers were silenced when Stephen MacKenzie in London in the same year not onl y demonstrated microfilarial periodicity in a 26 year old patient who had acquired the infection in India but. The animal was killed with prussic acid and Manson found that most of the microfilariae were in the lungs 163. he had an opportunity to prove that the same phenomenon occurred in humans. Manson concluded: Filaria nocturna during its temporary absence from the cutaneous circulation is present in the larger blood vessels.614 A History of Human Helminthology daytime attendant but he did not arrive at the correct explanation. the discharge commencing soon after sunset and continuing till near midnight. By 2 or 4 o'clock till 6 they are nearly completely absent. Manson repeated the procedure in three patients and found partial or compl ete reversal four days later 162. He wrote to Cobbold in a letter dated 27 February 1880: The young escape into the circulation at regular intervals of twenty four hours. On 1 9 February 1897. or whether they hid themselves during the day. In 1881. Meanwhile.. H e tried to investigate this with a dog inf ected with D. Cobbold presented Manson' s communication to the Quekett Microscopical Club on 27 February 1880 160. Closer analysis of these results revealed that more microfilariae were found on busy days when the blood examination had to be left to the evening.30 in th e morning.It is marvellous how nature has adapted the habits of the filariae to those of the mosquito. however. particularly the arteries. WW Myers o n Formosa (Taiwan) confirmed Manson's observations 180.. In addition. This reminded him of the earlier discrepancie s with his two assistants. 108. but most other authors fro m Manson on 14. In 1896. bancrofti was seen93.e. RECOGNITION OF THE CLINICAL FEATURES Swollen legs have been recognized since an tiquity. especially whe n associated with lymphatic thickening of the scrotal tissues have probably been . reported that there were two distinct patterns of microfilarial periodicity in B. In 1912. occurring in wild and domesti c animals. a considerable number in the muscle of the heart. then Wilson and his colleagues 236 . Germany. In addition to the previously recognized periodic for m which was transmitted by Anopheles mosquitoes and was endemic in open rice fields and swamp areas. there are many causes of hydrocele. the most common cause in endemic areas has undoubtedly been filarial parasites. malayi infections in Malaya. Lichtenstein in 1927 showed that the new microfilaria in his area. when h e visited northeastern New Guinea and parts of eastern Indonesia. Similarly. but the majority are lodged in the blood vessels of the lungs.124. This strain was shown to be transmitted by Mansonia mosquitoes. Fülleborn showed that this aperiodic form of W. Turner and Edeson 230.171 have thought it far more likely that periodicity depends upon an interaction between the microfilaria e and the host. onl y nocturnally periodic W. being found in the blood both by day and by night228. like that of W. The central thesis proposed by Lane 126 was that there was a cyclical release of embryos from adult worms. and was found to be a zoonosis. In 1957. In gross cases with thickening of the skin. late r named B. a few in the vessels of the kidneys. a subperiodic form (i. While the commonest cause of subacute cases of this condition is conges tive cardiac failure and even though relatively frequent problems such as deep vein thrombosis and rare conditions such as Milroy's disease (congenital absence of the lymphatics) and Dercum's disease (lipomatosis) may have accounted for a proportion of patients wit h chronic enlargement of the limbs. the resemblance of the limb to that of an elephant's leg led to the description of the condition as "elephantiasis". especially cats and monkeys 79. Whereas he found aperiodic W. then this observation was confirmed by Lynch in Fiji145 .166 The mechanism by which this phenomenon occurs has attracted a great deal of attention since those early days but still remains a mystery. bancrofti was present only eastwards of approximately 140oE longitude. microfilaraemia occurre d throughout the 24 hours with a mild peak at night) was seen among inhabitants of forested areas. Thorpe reported that the microfilariae seen in Tonga in the south Pacific exhibited no nocturnal perio dicity. was nocturnally periodic. but again. bancrofti 137. malayi. the majority of such cases in endemic areas. with microfilariae retiring to the viscera during the daytime. bancrofti in Samoan troops stationed in Hamburg.Filariasis 615 the capillaries of the muscles and brain. 127. malayi).138 While legs appeared to be affected most in this region (and was possibl y due to B. Thomas . Ralph Fitch.. was sent to the Malabar coast of India (Kerala) as factor of drugs from 1512-1515.. as described by John Barbot in 1732: Here is another unknown and foul distemper.in fact about a quarter or a fifth of the total population. i. nor do they take notice of this infirmity. a Roman living in the century befor e Christ. and was later to become ambassador to China. T Lucretius Carus. Elephantiasis was also known in West Africa and has been reproduced in ancient works of art. the tradition arose that Thomas. Descriptions of hideous deformity have been provided in more recent times. The Dutchman. son of King John II of Portugal.000 BC) shows pronounced enlargement of both legs which may be due to filariasis112. including the people of the lowest castes . and they have no pain. in the museum of Jos in Nigeria. who had lived in Goa between 1588 and 1592..500 BC-200 AD) whic h reveals elephantiasis of the scrotum 112. who had been apoth ecary to Prince Alphonso. a pharaoh of the XI Dynasty (about 2.616 A History of Human Helminthology due to filariasis. Similarly. gave the followin g account: they say that the progeny of those that slew him. Thomas 128. and it is an ugly thing to see. both men and women for that thereabouts there are whole villages and kyndreds of them that are borne in the said land of St. and in Quoya. Later that century. the disciple of Christ.have very large legs.. 88 Indeed.. there is the torso of a terracotta statuette of the Nok period (c. and many of them are scant able to go.. involvement of the genitals appears to have been mor e common in West Africa. are accursed by God.29 .which causes violent pains. a figurine recovered from a Mayan temple in Yucatan. dating from around 500 AD displays gross scrotal swelling 2. Central America.215.193. Nayars as well as Brahmans and their wives . an Englishman living in India described th e same condition at Cochin: This bad water causeth many of the people to be like lepers. the Blacks are subject to. John Hughen van Lin schoten. Tomé Pires. This in turn led to the legend that this illness was th e result of the curse of St. a wonderful swelling of. or in the Scrotum.. he wrote: Many people in Malabar.whereof I have seen many. had lived an d preached in that part of the world and was there slain with a lance whil e praying in the church. but only the unsightliness and evil favoured fashion.e.the swelling is the same from the knees downward. which is that they are all borne with one of their legges and one foote from the knee downwards as thick as an Elephantes legge. The Portuguese.. A statue of Mentuhotep I II. In the record of his experiences. swollen to a great size. stating that elephantiasis arose along the Nile and was facilitated by the climate o f Egypt: "est elephas morbus qui propter flumina Nili signitur Aegypto in media nequen praetera usquam" 144. and they die of this. For exampl e. and hinders their co-habiting with women. . throughout all the country about Sierra Leone. regarded elephantiasis as a characteristic disease of Egyptians. They have no let nor trouble in their going.. and many of them have legs swollen as big as a man in the waste. . A third clinical syndrome. the patient had not the least sexual desire. admitted into the surgical ward of the College Hospital. Calcutta on the 20th November 1843. chyluria. quite white. one yard and a half [135 cm].. The following are the dimensions taken in the erect position. the armchair reviewer back in the comfort of England facilely remarked that with such opportunities. bilious temperament. was also recognized. indurated in appearance. with filarial parasites unfolded only slowly. an emaciated. One such patient was recorded by G eorge Bonyun in Georgetown.36 The relationship between these chronic conditions. sickly-looking native Christian. brawny. ou r knowledge of the nature and cause of this formidable disease should have been advanced even more that it had been by the communication unde r consideration. has enjoyed good health for several years. and the spermatic cords could be felt easily on either side. and separating after remaining some hours into a substance resembling curds and whey. so as to resemble blancmange ... The diseased mass removed at operation weighed 70 lb [32 kg] and would have weighed eve n more had not the fluid that it contained esc aped..June 8th. aged 23.. firmly coagulating. until the urine acquired a milky appearance. as well as acute inflammation of the lymphatics. oedematous. circumference. Clinician s gradually separated Elephantiasis Graecorum fro m Elephantiasis Arabum. general shape ovoid.. British Guiana (Guyana) in 1846: H.95 The tip of the penis was buried at the end of a tunnel 10 inches [25 cm] deep. with an enlarged scrotum.. and causing him by its bulk and weight great difficulty in moving about. hanging down nearly to the level of the ankles. The record size for an enlarged scrotum was probably that reported by Pelletier who operated on one whic h weighed 100 kg 192.Urine decreased in quantity.. it became apparent that Elephantiasis Graecorum was leprosy and that Elephantiasis Arabum wa s filariasis. There was considerable confusion in the minds of many concerning thi s complex of diseases. With the discovery of the organisms causing each condition.urine. on the 8th May observed that his urine was turbid of a brownish colour.. three pints daily. and extending down nearly to his knees.. as will be described in . and was for a number of years the subject of much controversy.Tenth month. the integument over the pubes was not much implicated in the disease. Not surprisingly. feels dense. An even worse case in a 30 year old Indian living in Madras was described by Godfrey in 1851: The tumour is of immense size..white. good constitution.K. length from superior to inferior part 26 inches [65 cm]. aged thirty-one. although it s relationship with the other presentations of filariasis was not appreciate d immediately.-. the prepuce presented a knotty appearance in the centre of the tumour. Two forms of elephantiasis were described. creole of Demerara. and coagulating immediately after being passed.Filariasis 617 A particularly gross case was recorded in t he India Journal of Medical Science and abstracted in The Lancet in 1844: Moodoosudun Dos. this turbidity increased from day to day.. 4 After having reviewed the operative treatment. After separating the condition from leprosy. When infection with Brugia malayi was differentiated.. from erysipelas. During the second world war. and from a want of tone in the lymphatics. CORRELATION OF INFECTION WITH PATHOLOGY AN D CLINICAL FEATURES Although the pathogenesis of elephantiasis was a matter of much dispute. Several hundred American servicemen stationed in the south Pac ific. and none of them had either elephantiasis or microfilaraemia 229. the symptomatology in malayan filariasis was found to be broadly similar to that seen in bancroftian filariasis. Lesions in a limb usually began as a lymphadenitis which then spread in a retrograde or centrifugal fashion . His views were echoed by Brug 41 and many subsequent workers.119. some authors gave the name "filariasis". There w as a tendency to multiple involvement and recurrence. Lichtenstein in 192 7 observed that acute filarial disease was infrequent and that even thoug h elephantiasis was common. a term which Cobbold damned. was doomed. who h ad spent many years of residence in British Guiana was remarkably accurate in his perception of the problem.. The minds of not a few United State s servicemen were distressed by the possibility that these symptoms were a harbinger of hideous deformity yet to come. He was eventually proven correct.. although acute inflammation was recognized from time to time and genital disease was seen occasionally. an opportunity arose to study the clinica l manifestations of early filariasis in detail. and the persistence longer of each attack.618 A History of Human Helminthology the next section. although there were differences in emphasis. His opposition. for when Trent reviewed these patients 15-16 years later. the inflammatory action at each accession seemingly penetrating deeper. however. this was generally restricted to the lower lim b without involvement of the genitals 137. bancrofti.. Acute inflammatory lesions were seen in persons who had been in the endemic area for three months or more. became infected with W.viz. To this constellat ion of disorders. bellowing that "this vague and too comprehensive sort of nomenclature cannot be allowed to stand" 62. it is not until after repeated attacks of the disease. Babione in 1945 wrote a reassuring article entitled: "A few facts about filariasis for folks who fear that filaria-infected fellows will fetch f ilariae from the front" 18 in which he predicted that few individuals would suffer serious consequences and divined tha t development of microfilaraemia and secondary transmission was unlikely. E Bascome. an English surgeon. involving the whole of the subcutaneous . that enlargement of the part ensues.When the sequelae of erysipelas. the attacks generally lastin g for a few days and being associated with fever in about 20% of cases 76. he wrote in 1845: I am induced to think the hypertrophy is caused in two ways . particularly in Samoa. while genital involvement was indicated by a highly characteristic scrotal lesion with funiculitis and epididymitis. he found that only less than 1% had a swollen leg or genita l complaint. he had no suc h opportunity before his death five years later 239. When Demarquay discovered worms in hydrocele fluid in 1863.Should the scrotum become fastened on.It is unattended by fever or discoloration. attaining in some cases to an enormous size.lymph exudes profusely forming crusts.... a weariness is felt along their course in the limb. to the flow of the nutritive fluids of the body in various channels. but which may. and ultimately be the cause of death. Lewis. this convinced him that his previous proposal of a causal relationship was correct.30 Nevertheless. however.intersected.. Further. becomes studded with stone-like excrescences. Lewis connected microfilaraemia only with chyluria. had no such compunction when he indicated his discovery of microfilariae in the bloodstream of patients. Unfortunately.. and run into one confused mass. In like manner. and a benumbed sensation. Bascome had no idea what was the underlying cause of thes e changes and put them down to climatic conditions... During his first tour of duty in Amoy. give rise to serious disease. when Wucherer published a report of his finding parasites in chylous urine in 1868. with so little sensation as to admit of its being kicked like a football. however. The phenomena which may be induced by the blood being thus afflicted are probably due to the mechanical interruption offered (by the accidental aggregation. which degenerating into a variety of shapes. The involvement of th e lymphatics was confirmed a few years later by surgeons working in India 83.. and if the surface be abraded.. When it commences in the lymphatics.. in one case. perhaps. a pretty frequent concomitant.. Lewi s suggested that these problems were due to lymphatic obstruction which was in turn possibly a consequence of either encysted mature worms or migratin g immature worms in the lymphatics. on the contrary.which may continue in the system for months or years without any marked evil consequences being observed. he also refrained from conjecturin g about any aetiological relationship between the worms and haematuria and chyluria until he had the chance of examining a cadaver of an afflicted patient at autopsy. some of whom ha d chyluria: The blood of persons who have lived in tropical countries is occasionally invaded by living microscopic Filariae. when amputated. the scrotum weighed ninety two pounds avoirdupois...... on the other hand. he fou nd microfilariae in the blood of 11 patients or in one or other of the tissues or secretions in 30 individuals. Manson had encountered a number of examples of elephantiasis and had concluded from his surgical observations that the scrotal disease ...with weeping fissures.132 At first.The parts by-and-by become thickened into lumps. a puffiness and intolerable itchiness are present. of the Haematozoa). he wa s admirably cautious about drawing any connection between the two events.. Since all of these persons suffered from either chyluria or elephantiasis. or the result of the activity of liberate d microfilariae 133.. extensive partial disorganization.. As he continued his observations... but invited others to report any similar observations 73. giving rise to obstruction..hydrocele is. filling a pork-barrel! The testes are usually sound.Filariasis 619 cellular substances producing infiltration of that tissue and ultimately. The views of Lewis were soon supported by Manson. published a pa per in 1878 denigrating the work of these "recent writers"90. On his return to China after furlough in Britain .620 A History of Human Helminthology was "a sort of dropsy" 154. Manson was convinced that he ha d proven that these diseases were due to the worm. then reprinted in the Medical Times and Gazette 158. In the meantime. Fayrer replied that while he did not stand up as the champion for the filarial theory of th e disease. conclude d that the essential feature was obstruction of the lymphatics by these parasites. confirmation of the existence of lymphatic pathology was provided by Bancroft's discovery of an adult worm in a lymphatic abscess. a London dermatologist. . the association was of great interest and he considered. the infection was unisexual. and explained the latter on the basis that the worms h ad either died. and like Lewis. moreover. Nevertheless. Following a presentation of two cases of elephantiasis b y Joseph Fayrer at a meeting of the Pathological Society of London 84. Although the tests of experimental infection an d post-mortem examination were wanting. Fo x claimed that it was not proven that elephantiasis and lymph scrotum were the same disease. that the observations of men working in the tropics should not be disparage d because it was a very different thing researching in China and India compared with similar undertakings in London 91. and was consistent with his subsequent recovery of them from hydrocele fluid 20. Manson examined 190 local people who were selected randomly. and the somewhat less common reverse situation. there were still opponents of these ideas. claimed to have seen cases of elephan tiasis in patients who had never left England. together with his observations on the development of larvae within mosquitoes. Nevertheless. These clinical findings were published. Among these individu als were patients with lymph scrotum. To this.the not infrequent presence of microfilaraemia without disease. chyluria and inguinal lymphadenopathy . During 1877. or that the adult parasites had become encysted so that the larvae could not escape . elephantiasis. or recurrent attacks of fever accompanied by oedema which was not due to heart disease or renal failure155. some 60% of these patients had microfilaraemia compared with less than 10% of the normal population. in the Customs Reports 156. Fox again asserted that evidence linking filarial infections with elephantiasis was ver y weak. the onl y requirement being that they were willing to have a finger pricked. Manson noted that some of thes e infected persons were in perfect health but that others had evidence o f lymphatic obstruction with lymph scrotum. he appreciated that ther e were two unresolved problems . he confirmed his investigations and found parasites in 62 of 670 persons. Furthermore. and emphasized the abs ence of microfilaraemia in some patients with elephantiasis or chyluria. and cont rasted that with the extremely high frequency of microfilaraemia that Manson had observed in China. Manson thought that the former merely indicate d that the disease was merely an accidental side-effect. and argued that the escape of chyle in the urine and effusion of lymph into the tissues were two quite different matters. Dr Tilbury Fox. elephantiasis of the leg or genitalia. he foun d microfilariae in the blood of 15 of them. a mob gathered outside shouting death to the foreign devils. usually in the scrotum or thigh 162. Manson believed that the parent worms may sometimes die. by the bitter antipathy which the Chinese had to examination of the body after death. and suggesting that chyluria was due to rupture of distended lymphatics146. He postula ted that the ova are then caught in the nodes where they cause stasis. but in many other respects he was right in his interpretation of the sequence o f events. Many of the sceptics were silenced (Fox having died in the interim) when in 1882 MacKenzie presented the post-mortem findings in the patient in whom he had succeeded in reversing filarial periodicity once before. regurgitation of lymph. thus confirming t hat the habitat of mature filariae in humans is the lymphatic system. The flaw in his argument. Autopsy revealed that the thoracic duct was obliterated and embedded i n inflammatory tissue. pneumonia and pyelonephritis . however.Filariasis 621 Stimulated by Fox's criticisms. On an earlier occasion. The young man had died from an abscess near the clavicle. and succeeded in aspirating microfilariae from the glands. giving rise to an abscess. and they had to flee for their lives 174. and hypertrophy of the tissues. Moreover. He noted tha t inguinal lymphadenopathy was prominent in all these patients. even in patients with elephantiasis of the legs and normal genitals who had no microfilariae detectable in th e blood159. There is little doubt that Manson himself would have advanced the understanding of the pathology of filariasis much more rapidly if he had had the opportunity. sometimes going on to produce lymphorrhoea or chyluria. the fact that these lesions had no t . lymph scrotum. Manson and his brother David had paid a widow 200 dollars in return for permission to make a limited examination of a man with elephantiasis and microfilaraemia. hydrocele and elephantiasis) that had been associated with filariasis 196. was the idea that fe male worms "miscarried" with release of ova. An illustration of th e difficulties he went through in this cause is recounted in chapter 11 where his accidental discovery of Sparganum mansoni while looking for adult filariae is described. depending upon the si te of the obstructed lymphatics. Despite all these evidences. anastomosis o f lymph vessels. Prout in 190 8 forcefully advanced the view that filariae were not the cause of either the inflammatory disorders (lymphangitis and abscess) or obstructive lesions (lymph varices. On two occasions. While they were engaged in the autopsy. and that the ly mphatics below the obstruction were dilated enormously. Manson over a period of nine month s collected a series of six patients who were in a transitional state or who had a combination of elephantiasis of the limb and lymph scrotum. He was hampered. He based his arguments upon epidemiological observations that filariae were not alway s found even though the vector was present. of course. This observation caused him to evolve the theory that adul t worms live in the lymphatic vessels distal to the draining nodes and that they sometimes expelled ova prematurely. he recov ered ova rather than microfilariae from the lymph nodes. In the 1930's. in 1915. In contrast. It was opined. and 21 abscesses grew streptococci in pur e culture. He investigated 39 cases of acute filarial inflammation and found that blood cultures and microbiological studies of aspirates from inflame d tissue were uniformly negative whereas bacteria were always isolated from a control group of non-filarial abscesses 148. The role of the worm was thus relegated to that of a foreign body which acted as a focus for the opera tion of bacteria. that neithe r lymphangitis nor elephantiasis occurred to any great extent in the absence of W. Prout postulated that bacteria produced the acute inflammatory lesions and that recurrent attack s caused the obstruction of lymphatics. He concluded that adult worms and their larvae were entirel y responsible for the acute inflammation and chronic obstructive changes see n in filariasis. Meanwhile. In 1931 McKinley reported the results of a study designed to answer th e question: "Can we have acute filarial lymphangitis without bacteria l infection?"148. bancrofti 98. bancrofti and these complaints. the usual cause of which was a beta haemolytic streptococcus. and staphylococci in 22 cases 1. More importantly. Despite formidable opposition fro m Manson170 and others including Low and Manson-Bahr 143. this concept slowly gained ground. streptococci in 41 patients. Consequently. Anderson and his colleagues working in the same country a few years late r found adult worms in only one of 48 abscesses. four grew Staphylococcus aureus. the pendulum began to swing back in favour of the parasitic cause of the problem. Indeed. the Royal Society and the London School of Tropica l Medicine in 1926 launched an investigation into the bacterial complications of filariasis in British Guiana. however. and his own pathological studies in which serial sections o f involved tissues revealed large numbers of parasites but no evidence o f bacteria. however. and the record by Maxwell in 1901 177 that he had found remains of adult filariae in only one of 23 abscesses. Complete worms or pieces of adult filariae were found in the advanced pus in 22 patients. FW O'Connor then re-emphasized the correlation between the presence of insect vectors of W. This belief in an . the failure of McKinley to aspirate streptococci in filaria l lymphangitis. The report published a few years later concluded that a "filarial attack" was really lymphangitis. lymphangiticus and which they believed was "the cause of those disease s grouped under the designation of 'filariasis'" 77. Wise and Minett in British Guiana (Guyana) had studied carefully 28 abscesses and had found evidence in favour of both helminthic an d bacterial causation.622 A History of Human Helminthology been produced experimentally. despit e microfilaraemia being present in almost al l of the patients. he believed that living worms produced n o serious pathology but that the tissue reactions were usually in response to death of the worms and were probably allergic in nature 185. Dutcher and Whitmarsh announced th e "discovery" of a bacterium similar to Bacillus subtilis which they called B. and three were sterile 238. the lack of correlation between chronic filariasis and bacteria l infections. bancrofti microfilariae disappeared from the blood in a little over five years 114. but a prepatent period of between 67 and 98 days has been found in experimental monk eys188. Thus. A clue may be given to the diagnosis by finding an eosinophilia. to be when the adult worms had died . A number of approaches were therefo re used to enhance diagnostic ability. Lewis discovered microfilariae in the periphera l blood131 and Manson found them in lymph node aspirates 159 . but has not been proven. although there has been a report of microfilaraemia in the blood of a Frenchwoman who had not lived in an endemic area (Tahiti) for 40 years 49. and the development of techniques for the concentration o f microfilariae from the blood. pahangi 80. but this does not provide an aetiological diagnosis. Rarely . This is presumed. It was soon realized. Nevertheless. microfilaraemia developed 84 days after infection of a human volunteer with B. a n observation that was first made by Gulland in 1902 102. being seen not only in other tissue helminthiases. malayi was unsuccessful.232. Demarquay found microfilariae in hydrocele fluid 73 then Bancroft recovered adult worms from the same source 20. Similar deductions have been made by other investigators. Jachowski and hi s colleagues studied filariasis in Samoans in Samoa (the endemic area) and i n Samoans in Hawaii (a non-endemic area). calcified worms have been noted to produce opacities on X-ray examination. Such an experiment has never been undertaken with W. An attempt to infect a human similarly with B. particularly in the thigh and groin 186.Filariasis 623 immunological reaction was supported when large numbers of early . especially in patients with gross obstructive disease. . Wucherer demonstrate d embryos in the urine 239. however. As mentioned earlier. The prepatent period of filarial infections in humans has not been defined well. but also in a variety of unrelated conditions. but als o that microfilariae could often not be demonstrated in the bloodstream o f infected persons. that this was a very nonspecific finding. These included the assessment of immunodiagnostic tests. inflammatory filarial lesions in Ame rican troops were biopsied and histological examination revealed a typical picture of granulomatous lymphangitis 107. but recently Cross and hi s colleagues have infected Taiwan monkey s (Macaca cyclopis) with this parasite and obtained prepatent periods ranging between eight and eighteen months 66. The life span of the adult worms is also unclear. DEVELOPMENT OF DIAGNOSTIC METHODS Ways of diagnosing filariasis became evident with the discovery of parasites in various tissue fluids or excretions as has been recounted in the preceding pages. biopsy of affecte d lymphatics. it rapidly became evident that not only were adult worms hard to find. bancrofti in humans. and calculated that W. malayi 101 antigens.624 A History of Human Helminthology Somewhat more specific were the immunologic al tests that were developed. Operative removal of diseased scrotal tissue has bee n practised for at least 150 years. Much effort was made to improve the sensitivity an d specificity of these assays by fractionating Dirofilaria antigens213. beginning with skin testing using Dirofilaria immitis antigen. This was also the basis for the much publicized "Knott's technique" which did not require (in his origina l description) centrifugation: 1 ml of blood was added to 10 ml of 2% standard aqueous formalin in a measuring flask and was allowed to stand for 12-2 4 hours .214 and by using W. he used a preparation of the locally available soap fruit ( Sapindus rarak. however.a compact pellet containing microfilariae formed under the action o f gravity121. Suganumu in Japan described essentially the same method i n 1921224. as described by Taliaferro and Hoffman in 1930 225.74. bancrofti 113 and B.5 ml of blood with 5 m l of a solution containing acetic acid (which haemolysed the erythr ocytes) then inspecting the centrifuged pellet for parasites32. More promising. have been recent attempts to measure filarial antigens in tissue fluids or circulating in the peripheral blood 105. The surgical treatment in 1853 of Moodoo sudun Das (referred to earlier) who was "anaesthetized" with laudanum an d brandy was recorded as follows: . been used five years earlier in both loiasis and filariasis by Smith and Rivas as is described in chapter 24. Experience of early. The development of concentration techniques has assisted greatly in the demonstration of microfi lariae in the peripheral blood.119. which contains saponine) to haemolyse red blood cells. The commonest practice over the years. since they differentiate between past and present infection and may provide an index of intensity of infection. and the independent development of th e same test as well as an assay for c omplement fixing antibodies by Fairley in the following year82.232. however.199. The same principle was employed by Haga in Indonesia 103. inflammatory filariasis i n American troops during World War II indicated that the diagnosis could b e made in many patients by biopsy of inflamed lymphatics 76. is the most definitive means of proving a diagnosis. More recently.107. filtration of venous blood through variou s microscopic filters has become popular in view of its simplicity an d effectiveness 33. has been to examine for th e presence of microfilariae in one or more drops (20 µl) of blood smeared on a glass slide. Morphological demonstration of the worms. Possibly independently. One of the first of these techniques used in filariasis was that of de Beaurepaire Aragão who i n 1919 described mixing 0. in fact. THE SEARCH FOR EFFECTIVE TREATMENT The treatment of the obstructive complications of filariasis has long exercised the mind of surgeons. This technique had. Filariasis 625 Professor Raleigh.....made two parallel incisions over each spermatic cord, commencing over the pubes, and extending down the tumour about 14 inches in length; after dissecting up each testicle, a semilunar-shaped incision was made transversely across the pubes, uniting the two former incisions. The penis was next dissected up, and the whole tumour removed by making two small lateral flaps, with a long catlin; the haemorrhage was mostly venous, and not great; two small arteries only required ligature.4 Remarkably, the patient recovered, as did 13 of the next such 15 patients . Similar operations were described by a number of surgeons 95,96,154. Dreadful as are the problems with enlargement of the genitalia , elephantiasis of the limb has proven almost unassailable. Compression of the limb was tried but found to be of only temporary benefit 87, although Knott 70 years later was more impressed with its usefulness 120. Carnochan in 1851 introduced the operation of deligation, or tying of the main artery to the limb 50. This procedure sometimes had disastrous consequences and was roundl y condemned 87,151. Surgical removal of the adult worms was investigated b y Maitland152, but since the procedure involved excision of the involved tissues, it had the manifest disadvantage of exacerbating lymphatic obstruction . Maitland's operation was criticized by a number of surgeons, and despite his plea that it was safe and effective 153, failed to find a solid place in the surgical armamentarium. Near the turn of the present century, Handley proposed an operation o f lymphangioplasty for the cure of elephantiasis, but he himself was doubtful as to its value106 and others were distinctly unimpressed 149. Kondoléon in Athens believed that lymph stasis occurred chiefly in the fascia in the non-tropica l cases that he studied, so he devised an operation in which a strip of fascia was removed in order to make a broad communication between the disease d subcutaneous tissues and the lymphatics in the muscles 122. In 1930, Auchincloss described another operation which was intended to lighte n elephantoid legs and remove focal tender spots by excision of large slabs o f skin, subcutaneous tissues and fascia 17, then a similar operation was described by Gorter97. These operations, however, were major procedures in gross cases (when they were most necessary), and at best gave only partially satisfactor y results. From time to time, various unorthodox therapeutic modes, including radiotherapy115,231 and protein shock therapy 142 have been tried to cure filariasis, but they have been valueless or even dangerous. The medical treatment of filariasis has proved almost as depressing as the surgical management. As early as 1846, Bonyun claimed to cure chyluria with the bark of the mangrove tree, but his account hardly makes convincin g reading36. Myers experimented with the effects of quinine, salicylic acid , arsenic and santonin on microfilariae in vitro, but concluded that the amount of drug required to kill the wo rms would be sufficient to kill the host as well 180. Lawrie in India in 1891 considered that chyluria could be removed wit h 626 A History of Human Helminthology thymol129, but subsequent investigators were unable to confirm his observ ations. Similar evanescent claims were made for methylene blue 89, salvarsan (arsenic) 39, pepper201, antimony 202 hectine226, anthiomaline 40 , and arsphenamine227. A vast number of other drugs were also tried and found wanting. For example, Chopra and Rao reported in 1919 that they had assessed 72 different drugs without finding any worthwhile filaricidal activity 52. Sulphonamides, however, were shown to be of some value in acute inflammatory filariasis , presumably because of their action on secondary bacterial infections 78. In 1947, Hewitt and his colleagues reported that a new piperazin e derivative, diethylcarbamazine, produced a rapi d disappearance of microfilariae from the blood of cotton rats infected with Litomosoides carinii and in dogs with Dirofilaria immitis infections, although there was little effect on the adult worms themselves 111. Clinical trials were then carried out in the West Indies by Santiago-Stevenson and colleagues : 26 patients with filariasis were treated and a striking reduction in the level of microfilaraemia was observed and toxi c effects were tolerable 209. Subsequent studies showed that the drug and it s metabolites did not have a direct effect on microfilariae in vitro or on microfilariae in hydrocele fluid. Hawking and his colleagues concluded that the drug modified the microfilariae in some way so that they were removed by the reticulo-endothelial system109,110. Despite the high hopes held initially for this drug, it has not revolutionized the treatment of filariasis, often having only a transient effect on microfilaraemia and sometimes precipitating acut e inflammatory reactions, especially in malayan filariasis, which may merel y accelerate the natural history of the disease. UNDERSTANDING THE EPIDEMIOLOGY The distribution and prevalence of filariasis was quite inexplicable unti l Manson discovered that microfilariae developed in mosquitoes. Even then , another 20 years were to pass before the method of transference back t o humans was understood. In 1908, George Low wrote a paper entitled "Th e unequal distribution of filariasis in the tropics" 141 as a result of his experiences of that condition in the West Indies. He emphasized that the dicta "N o Anopheles, no malaria" or "No Stegomyia fasciata [= Aedes aegypti], no yellow fever" could be extended to "No Culex fatigans or suitable mosquito, no Filaria nocturna"141. Low remarked, however, that what was more difficult to explain was why the disease should remain localized in certain parts of the world although the intermediate hosts were much more widely distributed. He noted that filariasis was perhaps the most tedious of all the tropical diseases of which to study the epidemiology, for: the only way to arrive at a conclusion of how many individuals in a given district are infected is to make exhaustive night blood examinations of the population generally.141 Filariasis 627 Nevertheless, countless inve stigators have burnt the midnight oil and hundreds of papers describing the distributio n and intensity of filarial infection in various communities have appeared since Low's time. These have all given rise to the same general conclusions, namely that human s are the only significant reservoir of W. bancrofti but that subperiodic B. malayi is a zoonosis, the prevalence of microfilaraemia in endemic areas increases with age or plateaus in adult life, the prevalence of disease with chronic lymphatic obstruction increases wit h age, and that vectors of filariae in clude species of Aedes, Anopheles, Culex and Mansonia. There are a number of physiological forms within the W. bancrofti complex, however, which differ in their capacity for development in variou s mosquito vectors211. Furthermore, it became clear that the transmission o f infection is remarkably inefficient. Hairston and de Meillon 104 first drew attention to this in 1968 when they showed that bites by an average of 15,500 mosquitoes carrying infective larvae were necessary for the production of each new case of microfilaraemia i n Rangoon, Burma. Furthermore, less than 1% of mosquitoes carried infective larvae. Infection only occurred because th e average person was bitten by around 100,000 mosquitoes per year. The distribution of filariasis is not static. The infection was probabl y brought to the Western Hemisphere by the transportation of infected slave s from Africa 212 and was introduced into the sugar canefields of Queensland by infected labourers from the south Pacific islands. With improving standards of living, the worm has disappeared from some developed countries such as in the southeastern USA212 and northeastern Australia147 . On the other hand, rapi d urbanization and industrialization without concurrent provision of wast e disposal systems has lead to an increased breeding of culicine moquitoe s (especially Culex quinquefasciatus) which, when coupled with immigration of infected persons from endemic areas, has resulted in the inception of, or a n increase in, transmission of the infection 200. THE EVOLUTION OF PREVENTIVE AND CONTROL MEASURES Means of preventing the exit of microfilariae from the host became obviou s when the uptake of microfilariae by mosquitoes was shown by Manson. These ways were either the eradication of the mosquitoes or the prevention of interaction between the insect and the human. The first was frequently impossible but there was hope for the latter with the us e of mosquito nets and the screening of houses. It was not obvious, however, that the same measures would prevent infection until it was discovered that infective larvae entered the host directly from the biting mosquito rather than by being ingested in water. Fortunately, these same measures were effective in the prevention of malaria and yello w fever, and it was fear of the latter devastating infections that usually stimulated the installation of antimosquito measures. Nevertheless, filariasis in its ow n right has also been the subject of control efforts. As early as 1900, an attempt 628 A History of Human Helminthology was made to institute a campaign against filariasis in Barbados, but although considerable attention was given to educational measures, little was achieved. This resulted in 1912 in a particularly ill-informed and racist editorial which compared the prospects for control in white Australia versus the black Wes t Indies: of course, the difficulty, even for Brisbane, would be finding the carriers....and this difficulty for native populations, such as the negroes in the West Indies would be almost insurmountable. In the same way, having found that a negro was a carrier, it would be practically impossible to make him sleep under a mosquito net, or to explain to him the danger he was to other people. This will always be the difference in dealing prophylactically with white and native populations. 13 and concluded that the destruction of the int ermediate host was the only feasible proposition. Nevertheless, attempts to control breeding of mosquitoe s (particularly those that were specifically transmitters of infection, a procedure known as "species sanitation") and obstructions to contact between man an d mosquito remained the mainstays of filariasis control until the introduction of the powerful chlorinated hydroca rbon insecticides (e.g. DDT) after World War II and the discovery of diethylcarbamazine in 1947. Modifications to the physical environment, in cluding elimination of polluted water in urban areas (C. quinquefasciatus) 68, water containers in Tahit i (An. polynesiensis) 176, and drainage of swamps (Mansonia) 187, have been tried with variable success. Insecticides, including chlorinated hydrocarbons an d organophosphate compounds, have been used to control larvae and adul t worms, but their expense and the evolution of resistance to these agents i s creating increasing problems 68. In areas where Anopheles species are the major vectors, house spraying with residual insecticides has resulted in the welcome byproduct of filariasis control 234. Major efforts to control filariasis with either mass or selective administration of diethylcarbamazine have met with littl e effect except in circumscribed island communities 100. Limitations of human-mosquito contact with flyscreens and the humble mosquito net offe r perhaps the most promising prospects for control. Despite pockets of success, more people are infected now than whe n Manson discovered the vector over 100 years ago, but the prevalence an d severity of filariasis would be even worse were it not for: the efforts of a devoted but largely anonymous band of health officers, entomologists and their assistants which have been responsible for mosquito control in all the major cities, towns and even many small townships of the tropics. These measures were rarely aimed specifically against the vectors of filariasis but more against the vectors of malaria and arboviruses. In many cities, the original purpose is forgotten and mosquito control remains an exercise in aesthetics which makes life more tolerable by removing 'nuisance' mosquitoes.182 Filariasis 629 TROPICAL EOSINOPHILIA In 1939, Meyers and Kouwenaar described a series of seven Javanese men who had lymphadenopathy and a marked eosinophilia. When the lymph nodes were biopsied, eosinophilic granulomas surrounding microfilariae were found . Nevertheless, observation for as long as three years failed to reveal an y microfilariae in the peripheral blood, n or were any adult filariae seen in excised glands. The patients had no evidence of lymphatic obstruction but two ha d asthma and two had haemorrhag ic nephritis so the authors suggested that these syndromes were possibly allergic reactions to filariae 178. In the paper immediately following this report, Bonne, in the same journal, describe d finding extraordinary eosinophilic granulomas with giant cells around microfilariae in the spleen of a Javanese man killed in a motor vehicle accident . Bonne thought that this condition was similar to that described by Meyers and Kouwenaar and suggested that the finding represented either an undescribe d phase in the life cycle of one of the common filarial species or a manifestation of an unusual filarial parasite 34. In 1942, Dhayagude and Amin in Bomba y reported a further 11 cases of microfilarial granuloma 75. Meanwhile, in 1940, Frimodt-Möller and Barton had described a series of 175 patients with what they termed a "pseudo-tuberculous condition" characterized by dyspnoea, eosinophilia a nd extensive, persistent mottling of the lungs on chest X-ray92. In 1943, Weingarten reported a condition which he had seen in 81 cases, and which he believed to be a new disease entity, that he calle d tropical eosinophilia. The illness was characterized by fever, paroxysma l cough, dyspnoea, wheezing, splenomegaly and eosinophilia while chest X-ray examination of the lungs disclosed a distinctive, disseminated mottling. I n contrast to Löffler's syndrome, the illness persisted for weeks or months an d responded to treatment with arsenicals 235. Weingarten could find no cause for the condition but noted that it was common in coastal regions. The relationship with the conditions described by Meyers and Kouwenaar and by Bonne was not immediately apparent and there was considerable speculation to its cause , although a parasitic aetiology seeme d likely. In 1944, Carter and his colleagues postulated that the cause was the cheese mite 51. In 1955, Winter suggested that tropical eosinophilia may be regarded as an accentuated state of sensitivity in persons infected with filariae 237. In 1957, Gault and Webb reported that liver biopsies in four children with tropical eosinophilia (including the typical pulmonary symptoms) showed a striking eosinophilic infiltration in the portal triads, then found similar changes together with granulomatous foci around nematode larvae in a surgical biopsy from a further patient with hepatomegaly 94. In the following year, Danaraj and his colleagues in Singapore noted that W. bancrofti microfilariae occurred in Chinese, Indians and Malays, but that eosinophilic lung was virtually confined to Indians. Furthermore, these latter patients had high titres of antibodies to D. immitis antigen and responded well to tr eatment with diethylcarbamazine. 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Stationery Office, London, pp 108-114, 1913. Abstracted in Tropical Diseases Bulletin 2: 93-94, 1913 239. WUCHERER OE. Noticia preliminar sobre vermes de una especie ainda não descripta , encontrados na urina de doentes de hematuria intertropical no Brazil. Gazeta Medica d a Bahia 3: 97-99, 1868. Translated in 117 640 A History of Human Helminthology Table 23.1. Landmarks in filariasis ___________________________________________________________________ Elephantiasis recognized from antiquity Demarquay and colleagues discovered microfilariae in hydrocele fluid Wucherer found microfilariae in chylous urine Lewis observed microfilariae in blood Joseph Bancroft discovered a female adult worm Manson found microfilariae in the stomach of a mosquito and observed their subsequent development 1879 Manson discovered the nocturnal periodicity of W. bancrofti microfilaraemia in China 1880 Manson reported finding microfilariae in aspirates of lymph nodes 1888 Sibthorpe isolated and Bourne described a male adult worm 1896 Thorpe reported the diurnal subperiodicity of the Pacific form of W. bancrofti 1899 Thomas Bancroft suggested that infection may be acquired via the proboscis of a biting mosquito 1900 Low demonstrated infective larvae in the proboscis of filariated mosquitoes prepared by Thomas Bancroft 1927 Lichtenstein and Brug described a different microfilaria which was named microfilaria malayi 1939 Meyers and Kouwenaar described a syndrome of marked eosinophilia and lymphadenopathy with eosinophilic granulomas around microfilariae in the lymph nodes 1940 Rao and Maplestone described the parental form of B. malayi 1947 Hewitt and colleagues showed that diethylcarbamazine caused a rapid disappearance of Litomosoides carinii microfilariae from the blood of cotton rats 1948 Santiago-Stevenson and co-workers demonstrated a similar effect in humans with bancroftian microfilaraemia 1958 Danaraj showed that tropical pulmonary eosinophilia responded to treatment with diethylcarbamazine 1960 Webb and colleagues demonstrated the presence of microfilarial granulomas in lung biopsies from patients with tropical pulmonary eosinophilia 1965 David and Edeson described the Timor microfilaria 1977 Partono and colleagues described Brugia timori, the parental form of the Timor microfilaria ___________________________________________________________________ BC 1863 1866 1872 1876 1877 Chapter 24 Loa loa and LOIASIS SYNOPSIS Common name: eyeworm causing Calabar swellings Major synonyms: Dracunculus loa, Filaria lacrymalis, F. loa, F. oculi humani, F. subconjunctivalis, microfilaria diurna Distribution: West and Central Africa Life cycle: The adult worms, 30-70 mm long by 0.35-0.5 mm wide, migrate throughout the connective tissues. Microfilariae are produced and released into the bloodstream; they appear only during the day, a phenomenon known as diurnal periodicity. When microfilariae are ingested by tabanid flies of the genus Chrysops, they develop over 10-14 days into infective larvae which pass to the proboscis and infect the host at the next blood meal Definitive host: humans, (subhuman primates) Major clinical features: recurrent, transient, urticarial, subcutaneous swellings (Calabar swellings). Occasionally adult worms are seen migrating through the subconjunctiva Diagnosis: clinical (obervation of Calabar swellings); observation of the adult worm in the eye; demonstration of microfilariae in the blood Treatment: diethylcarbamazine, suramin AWARENESS OF THE ADULT WORM Since the adult Loa loa is several centimetres in length and moves from time to time through the subconjunctival tissues of the eye, this worm must hav e been recognized by people living in endemic areas for many centuries past. The name of the first European to see and describe this worm, however, has been a matter of some dispute. When the Frenchman, Guyon, described a case i n 1864, he reviewed the literature and believed that the first recorded evidence of this parasite was a certain copper engr aving which he interpreted as showing the extraction of Loa loa from the eye48. This engraving, which had been drawn by the engraver and publisher, JT de Bry, appeared in 1598 in the secon d volume of a two volume work called Collectiones peregrinationum in Indiam orientalem et occidentalem (known as India Orientalis for short) 14. The text was concerned in part with the travels to Asia of the Dutchman, Huighen van Linschoten, and included, amongst other things, his description o f dracunculiasis on Hormuz island in the Persian Gulf (see chapter 26), an d recounted how the king blinded his relatives to prevent assassination an d rebellion. The first volume, which had appeared in 1597 in German and was 641 however. who was a surgeon on Her Majesty's brigantin e Dolphin. an d Ward91 and Grüntzig and Jennes46 have shown that there was no reference to this parasite in these accounts... the latter authors have argue d convincingly that these engravings were not scientific reproductions. Blot10 then Guyon47 in Martinique. Indeed. saw and removed one earlier in July 1768. gave the first account in English.with itching. and by many other writers. but were fashioned with the aid of de Bry's fertile imagination. On examination. and Loney in West Africa 62. This last-named author. When it approached the transparent cornea. A ship's captain from Guadeloupe brought him a young African girl six to seven years old in whose eye he saw: a motile small worm the size of a small thread. however. I saw that its movements were not straight but tortuous and oblique... He reported his experiences with this condition in 1777 8 . The first definitive account of the worm was published in 1770 by Mongin. In fact. One end was bigger than the other.642 A History of Human Helminthology then issued in 1598 in Latin. I observed a worm moving round and round the . but he: saw a worm which seemed to crawl superficially on the eye. a French surgeon who saw the para site at Santo Domingo in the Caribbean. she did.. I examined it and observed a small animal almost two thumbs in length. On stimulating it to move. and a sensation as if something was moving around in the eye. for his primary purpose was not to serve science but to offer entertaining literature to the educate d general public. in 1771. 75 Although Mongin was the first t o publish an account of the worm. the pains became more severe. the width of a violin string. it moved around the eyeball in the cellular tissue which unites the conjunctiva with the sclera. again in a negress.. Mongin wrote that there was no inflammation.. the reco rd of Lopez had been translated from Portuguese into Italian by Phillip Pigafetta in 1593 then into German by A Cassiodo r Reinus. Further cases were seen by Guyot in Angola (1778) 49 . He was called by the Count of Cockburn to see one of his black female servant s who had been complaining of a severe stabbing pain in the eye of 24 hours ' duration. I realized that it was between the conjunctiva and the cornea. Its Latin title began: " Vera descriptio regni Africani quod tamabincolis quam Lusitanis Congus appellatur per Phillipum Pigafettam . but when I tried to catch it with forceps. contained an account about Africa by th e Portuguese. He saw two patients in 1848: They applied to me..8 Bajon saw another case. E Lopez. the colour of the eye never changed and the small negress complained of no pain even though the worm moved in the way it did. his compatriot. there is no loiasis in the Persian Gulf. Clot Bey in Egypt (1838)18. the conjunctiva was inflamed. Bajon in Cayenne. In this patient. This view was accepted b y Blanchard9. and dark colored.MDXCVIII". who believed that Pigafetta was the author of this publication. although both ends were very pointed. have an almost continuous small watering of the eyes.it was one and a half inches long. Guyon connected the words Congo and 1598 in the title of volume 1 with the engraving in volume 2 and concluded that the engraving was indicatin g pictorially the removal of Loa from the eye.. the microfilariae did not all appear to be of the same size.Loiasis 643 cornea. Many of the early French writers referred to the worm as a "dragonneau " (i. This term was adopted by Cobbold who combined it wit h Dracunculus to name the worm Dracunculus loa 19. and Guyon labelled it Filaria subconjunctivalis .e. Gervais and van Beneden designated 48 it Filaria oculi 40. In 1905.. In 1845. and secondly. Mackenzie invited Partrick Manson to see the patient. Further detailed descriptions were then provided by Looss 63 and by Huffman and Wherry 51. Guyot. Mackenzie noticed that the microfilariae differed i n several respects from the well-known forms now called Wuchereria bancrofti. dracunculus or guinea worm). DISCOVERY OF THE MICROFILARIA AND DETERMINATION OF ITS RELATIONSHIP WITH THE ADULT LOA LOA In 1890. but it was not until 1895 that the British ophthalmologist. causing very little if any. the parasites did not have nocturnal periodicity and could thus be found by day and by night. Nevertheless. he confirmed that the parasites were of two sizes. The other form was about two thirds of the size and had more active motions. Dujardin placed the worm in the genus Filaria of Müller78 and named it Filaria oculi humani 26. In view of these pecularities. many other authors retained it in the genus Filaria and following the lead of Aitken i n 18661. in collaboration with Manson. the aetiology of this condition was no t understood at that time. 62 Worms were encountered by many surgeons subsequently.. irritation. but no adult worms could be found at autopsy. The French naval surgeon. then Castellani and Chambers in 1913 erected the genus Loa to house the worm which has since that time been known as Loa loa 16. that the local native name for the parasite was "loa" meanin g "worm"49. Manson had the opportunity of seeing another patient of Mackenzie's. beneath the conjunctiva. in his description of the parasite man y years later.neither of the dracunculi when extracted were found to exceed two inches in length. the worm was known as Filaria loa for many years. One of them resembled the microfilariae of W. The patient died the next day. In particular. who had seen several cases while cruising off the coast of Angola in 1778 mentioned. bancrofti and at that time. then Dubini called it Filaria lacrymalis 25. Manson had no doubts that that was precisely what it was.. When Manson examined Mandombi's blood on the evening of 2 December 1890. Argyll-Robertson. he also came from the Congo and had been placed in a lunatic asylum because of a . Stiles and Hassall placed the parasite in the subgenus Loa of the genus Filaria 89. provided the first detailed descriptions of the male and femal e parasites5. but it soon became clear this parasite was a different creature from Dracunculus medinensis . A few days later . Stephen Mackenzie of the London Hospital found microfilariae in the blood of an African from the Con go named Mandombi who was suffering from sleeping sickness (trypanosomiasis). although he made one important error initially. Manso n now thought that the large microfilariae from the African subjects wer e different from those of microfilaria bancrofti in that the sheath was mor e delicate. perstans. F. looking for differences from those of microfilaria bancrofti (this was before the introduction of Romanowsky stains) but found only minor variations. Manson may not have been quite so definite in his remarks. but in the patient with the large microfilariae. respectively 68. Manson called them Filaria sanguinis hominis major (i. He examined the periodicity of these microfilariae in detail. Filaria sanguinis hominis became Filaria sanguinis hominis nocturna. if these observations had been made after the discovery of the diurnal periodicity of W. but in the other he saw bot h of the types that he had seen in Mandombi's blood. In one. Although it was apparent that there was at least one and probably two new species of microfilariae. With the perspicacity of a true savant. In both patients. the nature of the parent worms was not immediately clear.67 As a result of all these observations. In order to differentiate these new microfilariae from the Filaria sanguinis hominis of Lewis.e. only the smaller forms were found. microfilariae were circulating in the blood during the day. These names subsequently became shortened to Filaria nocturna. Afte r recalling that the subcutaneous and subconjunct ival migrations of this worm did not seem propitious for transfer of t he parasite to a new host and noting that the embryos in the circulation might have a much greater opportunity of migrating . these parasites reached a peak in the middle o f the day and were absent at night. bigger) and Filaria sanguinis hominis minor (i. Manson then examined the blood of two blacks from Ol d Calabar who were patients of Dr Grattan Guiness. and that there was an absence of granular material around the middle of the body. Manson scrutinized parasites from this patient very carefully. As with that patient. thus proving that one type of microfilaria was not a transitiona l form of the other. bot h forms being of the same size and provided with a sheath. On examination of this patient's blood. he concluded that "man is liable to be the host of at least two. Later that year at the Seventh International Congress on Hygiene and Demography held in London he renamed these parasites on th e basis of their periodicity. Manson suggested that Loa loa was a likely candidate. if not three. however.e. and persistence of microfilaria throughout the 24 hours . distinct species of filarial haematozoa" 67. the smaller worm could b e found throughout the 24 hours.644 A History of Human Helminthology mental disorder. bancrofti in the Pacific by Thorpe in 1896. daytim e periodicity. diurna and F. Filaria sanguinis hominis major became Filaria sanguinis hominis diurna. However. he found the small forms. Manson wrote: the law of periodicity for the appearance of the major embryo is just the reverse of that which has hitherto been found to apply to the filaria sanguinis hominis of Lewis. and Filaria sanguinis hominis minor became Filaria sanguinis hominis perstans to reflect night-time periodicity. the oral movements were more marked. smaller)67. he corrected this mistake and related F. and that the normal periodicity had been disturbed by the peculiar habits of West African negroes who. Later. loa was restricted to Africa. The more mature embryos resemble in size and shape those of F. nocturna and F. examination of more adult worms revealed that th e enclosed embryos were sheathed and seemed very similar to both microfilaria nocturna (= W. they contended that microfilaria diurna was none other than microfilaria bancrofti. was in thinking that it was the smaller microfilaria which was th e embryo of Loa loa (this is now known to be the embryo of Mansonella perstans).28 mm in length whereas the latter were 0. bancrofti in mosquitoes. and that the location of the V spot (excretory pore) in these two forms was different. diurna from the blood of a patient with adult Loa loa infection had also been documented previously by Dr. perstans was endemic in both Africa and South America whereas the acquisition of F.29-0.Loiasis 645 via a blood-sucking insect in a fashion analogous to W. Rather. diurna. 71 Similarly. The absence of F. Eventually. He removed a female Loa loa from the eye of a patient and s ent it to Manson but unfortunately the investigation was not conclusive. the association remained uncertain. examination of the pat ient's blood failed to reveal microfilariae 5. If they are possessed of a sheath. bancrofti) and microfilaria diurna.15. and perhaps misled by Leuckart's observation that adult Loa loa contained embryos which had a general resemblance to those of W. I should say that they are practically indistinguishable from the parasites mentioned. and to look for F. An opportunity for undertaking both of these options presented itself to Argyll-Robertson in 1894-1895. loa was erroneous. but in consequence of the method of mounting. he made measurements on 30 embryos expressed from an adult Loa loa that had been sent to him by D r Currie in Lagos and found that they were the same as those of microfilari a . Occasional patients were noted in whom both F.21-0. it is impossible to say if they are possessed of a sheath or not.32 mm long. Annett. however. however. spent their nights in orgies 2. Logan in Liverpool. diurna to F. diurna in the bloodstream. Indeed . bancrofti except that they were smaller. he wrote: "Might it not be that the smaller o f these new haematozoa is the embryo of the filaria loa?" 67. diurna in the bloodstream of patients with clinical evidence o f infection with the adult Loa loa. George Low then made careful measurements of microfilaria nocturna and microfilaria diurna and concluded that the former measured 0. Dutton and Elliot studied microfilaria diurna in its natural habitat in West Africa and concluded in 1901 that Manson's hypothesis that thes e microfilariae were the embryos of F. when it became apparent that F. of course. but since many more patient s had had only one or the other. Two ways of confirming this hypothesis were to compare the embryo s within an adult Loa loa with microfilariae of F. loa were recovered from the eye an d microfilaria diurna were seen in the blood 11. they claimed. with Manson writing: The uterine tubes are stuffed with embryos at all stages of development. loa 69. Manson's error. Furthermore. Dyce Sharp reported characteristic differences among microfilaria loa. Furthermore. Mackenzie. was negated by a potentiall y disastrous experience undertaken by Gönnert in 1941 (disastrous in the sense that Gonnert could have given himself a fatal transfusion reaction or infected himself with. Finally. in contrast to nocturnally periodic microfilaria bancrofti. then others. therefore. hepatitis B virus).39. microfilaria bancrofti and microfilaria perstans when stained with supravital dyes and when fixed organisms were examined after different stainin g preparations 33. As already indicated. Low was unable to reverse the diu rnal periodicity by inverting the sleep habits of an infected patient. bancrofti female adult worms released microfilariae in a cyclical fashion (see chapter 23). The mechanism of diurnal periodicity in Loa microfilaraemia was and remains as much of a mystery as does the nocturnal periodicity of W. nuclei extended to the extreme end of the tail in the case of microfilaria diurna. Fülleborn's observations were confirmed soon afterwards by Fol ey36 and then by Meinhof 74. Fülleborn clinched the matter when he reported that in microfilariae stained with haematoxylin or Azur II. This theory. A few years later. Low's views were supported by Huffman who studied in detail the embryos in a living Loa loa 50 and by Foley who found simila r differences in the measurements of microfilaria bancrofti and microfilaria diurna in the peripheral blood 36. One theory which had been put forward by Lane was that W. Low mentioned in 1910 that in 1904 he had been unable to achieve such a reversal in a patient with Loa loa microfilaraemia 64. in loiasis at least. Mackenzie and Manson showed from the very beginning that Loa loa microfilaraemia had a peak in the middle of the day.646 A History of Human Helminthology diurna. for example. bancrofti microfilaraemia. this was one of the means by which Manson differentiated the new species and provided the basis of his name for it. He believed. this characteristic was identical in microfilaria diurna and in microfilariae obtained from adult Loa loa 37. He repeated this experiment in 1921 on a 28 year old man who had acquired loiasis in Nigeria and confirmed this observation by having him sleep by day and remain awake at night for six days and nights 66. In 1912. that there was no question of th e identity of Loa loa and microfilaria diurna and declared that the time had come for abolishing the name microfilaria diurna and substituting in its place th e term microfilaria loa 64. had shown that microfilari a bancrofti nocturnal periodicity could be reversed by inverting the sleepin g habits of a patient. In 1912. Indeed. FURTHER OBSERVATIONS ON DIURNAL PERIODICITY Sensitized by their previous interest in the nocturnal periodicity of microfilaria bancrofti. but only for 95% of the length of the worm in the case of microfilaria bancrofti. Fülleborn had reported that he had injected Loa microfilariae into mice and monkeys but had failed to . however. possibly after conversation with Manson.000 microfilaria loa and 112. He fed the bedbug. Robert Leiper. The failure to find microfilariae in the blood of many such patients . had sent specimens of mosquitoes an d sandflies which he and Manson had examined but had failed to detect an y developing filarial larvae 6. He wrote: "Some naturalists may be able. he predicted that the vector would be a blood-sucking insect of limited distribution in Africa an d with day-biting habits. migrans. ELUCIDATION OF THE MODE OF TRANSMISSION: DISCOVERY OF THE TABANID INTERMEDIATE HOST The manner of transmission of Loa loa was a complete mystery to the earl y observers who saw the adult worm. however. many species of mosquitoes. to indicate these animals" 67. Pulex irritans. and get deposited in the impure water and thus propagate the disease. Gönnert in Hamburg took this idea and collected 160 ml of blood from a patient from the Cameroon with a heavy Loa microfilaraemia and injected it intravenously into his own bloodstream almost immediately. Subsequently. misled other investigators into thinking that some other mode o f transmission must be operative. He calculated that he transferre d 1. although he cautioned that: the chief difficulty consists in determining how these embryo filariae escape from the bodies of those affected with the disease. Manson 72 then Sambon 84 suggested that the intermediate host of Loa loa should be looked for amongst the larg e blood-sucking flies of the family Tabanidae which bite by day and were known popularly as mangrove flies or horse flies. o r upon an interaction between them and the host rather than upon the adul t worm41. even at this early stage of the investigation. Argyll-Robertson postulated tha t embryos may be ingested in contaminated water. who had returned to Old Calabar..Loiasis 647 recover any worms from either the peripheral or lung blood 38. for he recorded in a subsequent report that his patient. 5 Argyll-Robertson must have later changed his mind. Thus.640. When Manson first described the microfilariae that eventually turned out to be those of Loa loa.. the periodicity was dependent upon the microfilariae themselves. Cimex rotundatus. He suffered from an unanticipated transfusion reaction but examined his blood at intervals and found that a definite diurnal periodicity persisted over the next few days . Fülleborn reported in 1912 that he had tried to infect mosquitoes with Loa loa but to no avail 38. and various other flies including Stomoxys calcitrans.Possibly the embryo parasites may be discharged along with some of the excreta from the body. . the flea. Clearly.000 microfilaria perstans. funded by a bequest to the London School o f Tropical Medicine by the late Lord Wandsworth. In the latter part of that year. went to West Africa an d undertook a series of studies designed to identify the vector of Loa loa. S. and from faulty sanitary arrangements find their way into drinking water.. fasciatus and T. T. development was rapid an d uniform60. dimidiata were infected. and the third was manifestly unfair in view of its impracticability and the doubtful ethics of such a procedure. Connal in which he described the findings on more than 2. They reported that the majority of embryos reached the abdomina l muscles within 24 hours of feeding. no illustrations or descriptions of the larvae were provided. at the height of World War I. socialis.8% of 2. silacea. and perhaps a little xenophobia coloured C ockin's comments. In Chrysops dimidiata and C. they migrated to the cephalic end of the body of the insect. silacea and 2. She observed that 0. of course. on th e grounds that the nature of the hosts o n which the flies had fed was unknown. the Connals conducted many feeding experiments on cases of loiasis with large numbers of flies. silacea) and found that 5. and no attempt wa s made to transmit infection by means of infected flies 20.255 C. then development took place in the fatty tissue surrounding the tracheae in the abdominal cavity. however. Leiper sent a telegram from Calabar to the London School o f Tropical Medicine on 27 December 1912 which was reported in The Times and the British Medical Journal of the following week: "The metamorphosis of Filaria loa has been proved to take place in the salivary glands in a fl y belonging to the genus Chrysops"61. While the first criticism was valid. A.in one insect. however. Growth was rapid so that by the fifth day they were seen coiled i n . his discovery was confirmed and this omission rectified by a number of subsequent investigators. dimidiata and 100 C. These criticisms were certainly not applied by an editorial writer in The Lancet 4 commenting on the report in 1921 by Dr. In 1915. T. A sligh t degree of infection was observed with Haematopota cordigera and Hippocentrum trimaculatum . Kleine considered that microfilariae perforated the gu t wall. because of a lack of f lies with which to work. Kleine reported the results of his investigations in a heavil y endemic area at Eseka in the German Cameroons (now called Cameroon).648 A History of Human Helminthology Glossina palpalis. the larvae were usually present in the muscles . but the development was slow and asynchronous. Tabanus par. a time which was not propitious for extended investigations on Kleine's part. 427 worms were present 21.000 Chrysops which were caught over eight months in 1917 near Lagos and then were dissected by his wife. secundus on a patient with Loa loa microfilaraemia but with negative results. He examined 600 wild-caught female flies (500 C.4% of 249 C. Leiper had to abort his studies in January 1913. the second could also have been levelled at Leiper. Nevertheless. This work was criticised by Cockin. however. This was.3% were infected. and in two cases he was abl e to demonstrate emergence of the larvae from the proboscis 57. Perhaps because he intended to extend his studies later. although others proceeded to the head and thorax. Later. Subsequently. Leiper does not appear to have published details of his observations on the development of microfilariae in Chrysops. He was informed that Chrysops had a marked seasonal incidence at Calabar in Nigeria and that they would not reappear in abundant numbers until June. with fully mature infective larvae bein g present in nine flies. They used infective larvae obtained fro m C. irritating sensation but not real . durin g which action the anticoagulant in the insect's saliva prevented clotting. migrated to the thorax. sometimes coursing over the surface of the eye under the conjunctiva. Gordon and Crewe studied the mechanism of feeding of C. silacea that had fed on a patient in the British Cameroons and found a prepatent period of 146 days in the baboon and 135 and 148 days in th e monkeys. Finally. but showed a preference for the left one. Ten to twelve days after infection. particularly of the abdomen. Microfilaraemia persisted for more than 40 weeks in the monkeys but began to decline after three months in the baboon 80. larvae migrated towards the head. Connal and his wife concluded that the forms found b y Kleine in abdominal fatty tissue were almost certainly. A detailed description was provided in 1895 by Argyll-Robertson who recounted th e symptomatology in a 32 year old English lady who had spent eight years at Old Calabar in Nigeria on the West Coast of Africa.23. accumulated at the root of th e proboscis and the labium and exited via the labella. She told him that: the worm frequented both eyes. The y showed that the infective larvae escaped from the proboscis during the act of feeding44 then Lavoipierre indicated later that the infective larvae escape d through a rupture in the delicate labio-hypo-pharyngeal membrane 58. silacea and C. evidence wa s procured which indicated that flies could remain infective for five to si x days22. while the latter believed that fatty cells in the haemocoele surrounded the larvae and fused to form a syncitium 59. This question was re-investigated many years later by Lavoipierre and by Lebied. RECOGNITION OF THE CLINICAL FEATURES The most dramatic clinical manifestations of loiasis were attended by th e appearance of a worm in the eye. and presumably entered through the wound made by the biting fly. Sometimes the parasite caused little trouble except perhaps a minor irritation or watering. stages in the development of Loa loa 24. Orihel and Moore in 1975 infected two patas monkeys ( Erythrocebus patas) and a baboon (Papio anubis).75. Gordon and Crewe also reported that the infective larvae could not penetrate the intact skin. dimidiata and concluded that they fed from a pool of blood formed in th e deeper layers of the skin as a result of several thrusts of the fascicle. they had to modify these comments since histological sections of infected flies prepared by Dr AC Stevenson had made it clear that most of the larvae were not in muscles but in fatty tissue.62.causing a tickling. after bursting o ut of them.Loiasis 649 whorls in the musculature. whereas on other occasions i t produced a severe stabbing pain or overt conjunctivitis 8. Soon afterwards. as he presumed. Although Loa loa has never been transferred to humans experimentally . sometimes wriggling under the skin of the eyelids . neck and head58. however. th e so-called "fat body". The former author considered that the young larvae invaded the cells of the fat body then. The patient in whom Manson first observed the micro filariae died of sleeping sickness and the second patient was insane.. Less definite were the suggestions of an association between Loa infection and cerebral disease.5 Moreover. The swellings measured about half an inch in diameter. however.. the patient noticed that she was troubled much more when sh e was febrile (from malaria) or remained indoors in a warm room or sat near a fire. and that the worm seemed to disappear to the deeper parts when her face was exposed to the cold. The surface of the swellings was not quite uniform. the secretion of irritating glandular products. he aspirated swellings of two patients who. Of these various hypotheses. The pathogenesis of these lesions was a matter of considerable debate .. Argyll-Robertson managed to extract an adult Loa from deep within the tissues of a similar swelling in the temple of a patient 5. It passed with a pretty quick movement over the surface of the sclerotic at the distance of about 5mm from the outer margin of the cornea. and failed to find any embryos.5 Furthermore. but occasioned a feeling of stiffness. They were not painful. Argyll -Robertson was able to observe a worm in the eye after the application of a warm cloth to her orbit: I observed the worm moving in a tortuous. over the dorsal surface of the radius.650 A History of Human Helminthology pain. he favoured the last. so Manson .5 Argyll-Robertson also drew attention to the other characteristic feature of loiasis which came to be known as "fugitive swellings" or "Calabar swellings". wriggling manner under the conjunctiva. or the periodical emptying of th e contents of the uterus of a gravid female worm into the connective tissues of the host. they were termed " ndi tot" meaning "swelling" by the local populace5. There was increased lachrymation and slightly increased injection of the conjunctiva. he thought it more likely that th e lesions were due to a toxic reaction to the worms. Manson postulated that the oedema might be caused b y lymphatic obstruction. possibly dead ones 65. did not have a microfil araemia. in contrast to Manson's case. and the eyelids to swell and blacken slightly. his patient told him that the natives of Calabar and others who had been resident there for some time were also subject to these swellings on the forearms and wrists. th e excretion of faecal material by the worm. Manson (1910) thought i t unlikely that the mere presence and movement of worms caused these lesions for he cited a patient whose blood was teeming with microfilaria loa and who amused himself by harpooning adult worms with a needle as they wriggled their way under the skin of his chest or abdomen. but did not give one the idea of being produced by a coiled-up worm. yet who rarely suffered fro m Calabar swellings. and supported thi s thesis by instancing his discovery of microfilariae in an aspirate of one of these lesions70. He remarked that his patient complained of: ill-defined swellings under the skin of the forearm a little above the wrists. the surface of which became slightly elevated as it moved along.The swellings occurred at irregular intervals. Finally. This could not be confirmed by Low. more marked generally in the right arm. occasionally causing the eye to become bloodshot. a regular crop of swellings kept coming and going. Johnstone recorded his own experiences: I first noted the gradual onset of a swelling above the right wrist. at other times they appeared to be situated more deeply.... Other conditions which have been associated with loiasis include endomyocardial fibrosis 52 and nephrotic syndrome93.. DEVELOPMENT OF DIAGNOSTIC METHODS The diagnosis of loiasis is obvious when a worm is seen moving around th e subconjunctival tissues of the eye.I had 16 swellings. Similarly. It was noted that the natural history of this infection may occupy man y years. which were painless yet occasioned stiffness.did I manage to sleep more than 20 minutes at a time. naturally-acquired infections. On the other hand.. By far the greatest number developed on the forearms. but the swelling gradually spread to involve the whole of the right hand. At times they were irritating and the overlying skin red. The adult worms may be very long-lived fo r instances have been recorded in which adult worms have persisted for at least 17 years73. for he recounted a case in which such problems began 61 days after the earliest conceivabl e date of infection and one week after the most probable infective date 34.. 3 coming on in one day. Later authors12. and writing for more than a few minutes caused cramp. a severe neuralgia in the distribution of the right median nerve came on every night and at no time. Rogers described fugitive swellings. there have been countless tales of sceptical but ill-informed doctors who found the story that their patient told .. At this stage.playing any games which involved holding a handle was impossible.. Several reports have been given by physicians of their own. In one week. These recurred. together with headaches. Meinhof reported the case of a female German missionary who went to the German Cameroons in 1903 and developed Calaba r swellings two years later. causing an ache which usually felt like a bruise and lasted 24 hours.54 Johnstone then went on to recount the removal of an adult worm from his eye on four separate occasions 54.87 described a variety of neurological problems in patients with Loa infections. Dyce Shar p demonstrated that clinical manifestations (Calabar swellings) could appea r soon after exposure. for another six years until an adult Loa was first seen 74. Neverthel ess. but these turned out to be coincidental. and recounted the migratory habits of the adult worm 82...Loiasis 651 canvassed the possibility that the two conditions were connected 68. A number of months usually passed after exposure before the first sign of infection appeared.. Within a few weeks of the appearance of the first swelling. especially around the joints. while trypanosomes wer e shown to be the cause of sleeping sickness. but few parts of my body have so far escaped. This was pronounced to be a sprain. personal .. and lasting about ten days.95.The swelling of the wrists and hand persisted for at least 6-8 weeks. The methods used in W. in Mansonella perstans 85 and Wuchereria bancrofti 13 infections. of Loa infection. it would come out by itself.0 ml of blood in 5 ml of 2% acetic acid. then finding microfilariae in the sediment87. a doctor with experience himself in the endemic area. It needs to be remarked. Loa microfilariae have been recovered from urine . that the first concentration technique was applied i n cases of loiasis and filariasis by Smith and Rivas. however. Bajon was more expansive in detailing the problems he encountered: After reflecting upon the ways in which I could extract it. bancrofti infections were equally efficacious in loiasis.1-1. Worse. immunologica l reactions to Dirofilaria have also been seen. reliance had to be placed upon pointers t o infection with Loa loa. It was realized gradually. was too non-specific to be diagnostic. however. I opened th e conjunctiva and extracted the worm through that incision" 75. although witch-doctors and their kin had been performing suc h procedures for centuries. Rarely. vice versa. but noted that this test did not differentiate among the various filariases. for example. wa s misdiagnosed in 1907). many patients with Calaba r swellings had neither evidence of an adult worm nor the presence of micro filariae in the bloodstream. An alternative method of diagnosis was apparent whe n Manson and Mackenzie discovered microfilaria loa and means were evolved for differentiating them from other filarial parasites. Although these lesions were very puzzling initially (even Rogers. The chances of making the diagnosis in this way were improved by various concentration techniques. sputum and cerebrospinal fluid 53. They reported in 1914 that the diagnosis could be enhanced by mixing 0.652 A History of Human Helminthology them too incredible. clinicians began to recognize them as characteristic. Mongin made it appear simple. THE SEARCH FOR EFFECTIVE TREATMENT The management of loiasis is essentially s urgical when the opportunity presents itself. that many patients with a history o f eyeworm had no microfilaraemia and. were among the firs t Europeans to report surgical extraction of the parasite. Mongin and Bajon. Fairley 35 and Rodhain and Dubois81 showed that intradermal injection of Dirofilaria antigen produced an immediate hypersensitivity reaction in patients with loiasis. and are discussed in chapter 23. I put this plan to . Eosinophilia was a characteristic finding 74 but although it tended to be higher than in other helminthiases. merely remarking: "In order to remove it. The French naval surgeons. and realized that parasitological con firmation of the diagnosis was likely if the patient was followed for lon g enough. In such circumstances. that many patients with Loa microfilaraemia had no such history. as has already bee n discussed. Slightly more specific were immunoassays. I believed that by making a small opening in the conjunctiva near the side of the head of the small animal. then after stimulating it to move. if not pathognomonic. shaking and centrifuging the mixture. diethylcarbamazine was introduced for the treatment of bancroftian filariasis (see chapter 23). when local anaesthesia was available.8 A century later. Although most authors agreed that there was no effective drug for the medical treatment of this infection. He tried many times to remove a worm from the eye of a 15 year old girl. this was said to either retain the worm on the sclera where it could be picked off with a needle. Maddox. evanescent claim s were made for salvarsan (arsenic) 76. as briskly as before application of the cocaine. The same sequence befell his next tw o patients.86. then this drug was soon tried in loiasis. Most of these patients had no Loa microfilaraemia. when the pressure of the finger having been removed the wriggling movements of the worm resumed.88. who was present.90. In Murgatroyd and Woodruff's series. Argyll-Robertso n recounted his technique: I at once placed my finger on the surface of the globe in such a manner as to prevent the parasite passing backwards until the conjunctiva was pretty well anaesthetised by the application of cocaine. taking care to include in the fold all the structures superficial to the sclerotic. Some patients developed an itchy morbilliform or urticarial rash after treatment (possibly due to concurrent occult infection with Onchocerca). the parasite came away readily. vari ous arsenicals and tartar emetic in loiasis but found them to be useless7. I pulled it out. On now relaxing the fixing forceps. In 1947. A number of investigators reported clinical improvement in many but not all patients with loiasis79. the negress was well within 24 hours. I then made a small hole at the side of its body with the point of a lancet. Seeing that this tentative method was not of any use. and he remarked rather optimistically that they had probably bee n cured by his application of cocaine 83. A number of drugs were tried in loiasis. Roth noted in passing that it was a common practice amongst the local inha bitants to treat the infection by packing small pieces of onions around the eye. only three of the 17 patients had microfilariae in the bloodstream. and with an ordinary needle. I then got my friend Dr. it passed to the side and went to the region opposite the incision. after this operation. but never succeeded in catching the elusive creature. I now grasped with a pair of toothed fixing forceps a good fold of conjunctiva over the centre of the wriggling worm. in such a manner as to lift up a small flap of conjunctiva. Roth told of his unfortunate experiences. which I seized with a pair of iris forceps. Aubert and Heckenroth (1913 ) investigated the actions of aniline. anthiomaline (antimony) 17 and picric acid77. and no mention was made of the longterm effects of the drugs on . for example. found one extremity of the worm. or drive it away (and he postulated that it passed through the nasal duct and was then eithe r swallowed or spat out!). She was placed on a couch and the speculum applied. and after a little careful separation of the tissues.Loiasis 653 action. to apply his finger while the necessary preparations were hastily made for an operation.5 In the following year. I grabbed hold of it at the middle of its body with small forceps as well as the conjunctiva. I next made with a pair of scissors an incision through the conjunctiva a little nearer the cornea. but instead of coming out through the aperture I had made. . though the former was muc h more common. . preferring the well-lighte d houses of Europeans to the d ark houses of the Africans. The factors influencing the distribution and intensity of infection could b e ascertained only when the central role of Chrysops flies in the transmission of infection had been ascertained .30 a.m. Chrysops larvae were found in densely-shaded streams. and to study th e habits of the vectors. wa s possibly transmissible to man 27. its universal occurrence in black slaves in the latter area and its spontaneous disappearance from that regi on indicated that Loa infection was endemic only in parts of West and Central Africa. although it had certain morphological differences and had nocturnal periodicity. but the most intensive efforts were made during the late 1940's and the 1950's. it cannot be relied upon t o eradicate the infection. They observed that the female flies bit once every two weeks or so. It became clear that infection was limited chiefly to the rain forest or its immediat e environs56 with the adult flies occupying the canopy of the forest. C. Furthermore. Sporadic attempts were made over the next few decades to both define th e prevalence and severity of disease in infected populations. UNDERSTANDING THE EPIDEMIOLOGY Although cases of loiasis were described initially from both Africa and fro m South America. Subsequent experience has shown that although this drug may be useful in patients with loiasis. thus suggesting that the action of the drug was t o sensitize the microfilariae which were then destroyed by the cells of th e reticulo-endothelial system 94. hunted probably by sight. and had infection rates of up to 12%. dimidiata were both found. Woodruff later reported the liver biopsy finding in a patient in whom diethylcarbamazine treatment had caused the parasites t o disappear from the peripheral blood.30 p. Gordon and his colleagues reported their investigations in a town in th e British Cameroons in which a quarter of the population were infected . usually between the hours of 8.45. were found indoors as well as outdoors. Duke then showed that smoke from woo d fires increased greatly the biting rate and may be an important factor i n attracting flies from the forest to feed in houses28. and 4.654 A History of Human Helminthology the microfilaraemia 79. siliacea and C. monkeys in those forests were infected with a strain of Loa loa which. microfilariae in the biopsy wer e surrounded by phagocytes.42. localized in the stagnant parts and in mud beneath decaying vegetation 43.m. and also suggested that the flies were attracted by movement 29. two volumes. 1913 8. Parasitic diseases. 1777-1778.. 4: 591-593. volume 1. 1897 7. 1866 2. This has proved almost impossible in areas where concurrent onchocerciasis increased greatly the incidence and severity of toxic reactions to the drug. Mémoires pour servir à l'histoire de Cayenne et de la Guyane française etc. 611-612. Filaria loa. Filaria loa and its insect host. volume 4. Control by mass treatment with diethylcarbamazine to reduc e microfilaraemia and repeated prophylactic administration of the drug have been proposed32. Paris. Case of Filaria loa in which the parasite was remove d from under the conjunctiva. but such measures have not proved very satisfactory. 1886 10. AITKEN W. In. 1904 . British Medical Journal i: 39-40. This latter idea was suggested by the demonstration by Duke i n monkeys30 and in humans 31 that diethylcarbamazine appeared to kill infective larvae. 1902 3. 1913 4. ANNETT HE. Paris. BAJON B. BLANCHARD R. HECKENROTH F. pp 799-900. Science and practice of medicine. ELLIOT JH. Comptes Rendus Hebdomadaires de la Société d e Biologie 56: 630-632. series 2.92. ARGYLL-ROBERTSON DM. Part II. Lancet i: 606. Cited in 47 11. AUBERT P. BRUMPT EJ. Transactions of the Ophthalmological Society of the United Kingdom 17: 227-232. REFERENCES 1. Progrès Médical . ANONYMOUS. 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Essai de traitement avatif de la filariose à Loa loa et de la filariose apériodique par les dérivés de la pipérazine. 1905 90. dieldrin. Journal of Tropical Medicine and Hygiene 6: 26. 1963 93. The effects of DDT. MOORE PJ. Annales de la Société Belge de Médecin e Tropicale 29: 73-80. 1787 79. STEFANOPOULO GJ. RODHAIN J. 1949 87. WILLIS AJ. MÜHLENS. Transactions of the Royal Society of Tropical Medicine and Hygiene 25 : 377-382. V. DWORK KG. United State s Department of Agriculture. 1905 92. Adult nephrotic syndrome at Ibadan. Journal of Tropical Medicine and Hygiene 60: 170-172. Naturforscher. WOODRUFF AW. The earliest record of Filaria loa. A contribution to the study of intradermal reactions in human filariasis. American Journal of Tropical Diseases and Preventive Medicine 2: 361-377. RIVAS D. SHOOKHOFF HB. WARD H B. Filaria loa. Studies on the control of vectors of loiasis in West Africa. Zur Behandlung der Filariasis. und besten Schriften. SCHNEIDER J. 1968 94. American Journal of Tropical Medicine and Hygiene 24: 606-609. American Journal of Tropical Medicine 29: 589-593. CREWE W. WILLIAMS P. Journal of Tropical Medicine and Hygiene 71: 513-517. loa par la 1-diéthyl-carbamyl 4-methylpipérazine. and Filaria bancrofti Cobbold). Remarks on the individuality of Filaria diurna. pp 1-150. Notes upon human filariasis ( Filaria loa Guyot. Annals of Tropical Medicine and Parasitology 7: 363-365. 1913 83. 1914 88. WOODRUFF AW. SCHOFIELD FD. Verzeichniss der bisher entdeckten Eingeweidewürmer.und Tropen-Hygiene 30: 626-628. der Thiere. ZIEMANN H. 1949 80. Lancet ii: 147-149. Ein Fall von Filaria-loa-I nfektion mit mindestens 17 jähriger Dauer. Transactions of the Royal Society of Tropical Medicine and Hygiene 44: 479-480. A note on a cas e of Loa loa. 1932 82. The determination of generic types. Essais de traitement de la filariose à F. i n welchen sie gefunden Worden. Comptes Rendus Hebdomadaires des Séances de l'Académie de Biologie 142: 930-931. 1948 89. aetiological considerations. Bureau of Animal Industry. SAMBON LW. 1949 91. ROGERS W. HASSALL A. MÜLLER OF. MURGATROYD F. DUBOIS A.Loiasis 659 77. Archiv für Schiffs. Archiv für Schiffs. 1975 81. ROTH F. Bulletin 79. aldrin and gamma-BHC in the mud of natural tabani d breeding-sites in the rain-forest of the Cameroons. SMITH AJ. 1903 85. 1926 . with their original and type species.und Tropen-Hygiene 25: 247-248. STILES CW. WANSON M. Destruction of microfilariae of Loa loa in the liver in loiasis treated with Banocide (Hetrazan). 1957 86. The complement-fixation reaction in loiasis and Acanthocheilonema perstans infections. 1896 84. Landmarks in loiasis ___________________________________________________________________ Adult worms migrating through the eye were recognized by inhabitants of West and Central Africa and were removed by local practitioners 1768 Bajon removed an adult worm from the eye of a girl 1770 Mongin published an account of the adult worm and the clinical features it caused 1890 McKenzie found unusual microfilariae in the blood of a patient with sleeping sickness 1891 Manson investigated several patients and differentiated a microfilaria of the same size as microfilaria bancrofti but which had diurnal periodicity and ill-defined morphological changes (= microfilaria loa) and a smaller microfilaria with no periodicity (= microfilaria perstans) 1895 Argyll-Robertson in collaboration with Manson gave a detailed description of the morphology of male and female adult worms Manson suggested that microfilaria diurna may be the embryo of L.1.660 A History of Human Helminthology Table 24. loa 1912 Leiper discovered that microfilariae developed in flies of the genus Chrysops 1914 Smith and Rivas described a concentration technique for the demonstration of microfilariae in the blood 1921-3 Connal and Connal described in detail the development of larvae in Chrysops 1948 Stefanopoulos and Schneider described the results of treatment with diethylcarbamazine 1975 Orihel and Moore infected two monkeys and a baboon experimentally using infective larvae developed in a fly fed on a human with loiasis __________________________________________________________________ BC . microfilariae that were easily detectable by virtue of their violent contortions 661 . mostly live coiled tightly in subcutaneous nodules. and succeeded at length in discovering a filaria which I believe to be the immediate cause of the complaint. leading to blindness Diagnosis: observation of microfilariae in the cornea or anterior chamber (best with a slit lamp). When he turned his attention to papules. John O'Neill. ivermectin. dermatitis. Filaria volvulxus.15-0. iridocyclitis. keratitis. anterior chamber and uveal tract of the eye.102 When specimens were examined in a drop of water under a microscope . choroidoretinitis. suramin DISCOVERY OF THE MICROFILARIA In 1874. demonstration of worms in excised nodules Treatment: diethylcarbamazine. O'Neill examined the contents of pustules and vesicles under a microscope but found nothing other than leucocytes. a British n aval surgeon attached to HMS Decoy at Cape Coast Castle in the Gold Coast (Ghana) became intrigued by an irritating and intractable skin disease somewhat resembling scabies which afflicted man y people living in parts of the West Coast of Afr ica. He determined to look for the cause of this peculiar condition. Microfilariae are produced and migrate through the dermis and into the cornea. they develop over a week or so into infective larvae which pass to the mouthparts and infect the next host at the following blood meal Definitive host: humans (gorilla. The condition was characterized b y papules. finding microfilariae on skin biopsy. Onchocerca caecutiens Distribution: West. When microfilariae are ingested by blackflies of the genus Simulium. by studying a number of patients in Addah Fort Hospital under the care of D r Thompson of the Glover Expedition. Central and northern South America Life cycle: the adult worms. spider monkey) Major clinical features: subcutaneous nodules.Chapter 25 Onchocerca volvulus and ONCHOCERCIASIS SYNOPSIS Common name: the convoluted filaria causing river blindness Major synonyms: Filaria volvulus.40 mm in diameter. He reported in 1875: I was induced to bestow much time on its microscopic examination. 20-50 cm long by 0. Central and East Africa. vesicles and pustules. success attended his efforts for he found a n organism which he had no doubt was the cause of the complaint. which was known locally as "craw-craw". volvulus was a strange and tortuous affair. It 1890. Whether the microfilariae found by da Silva Araujo were in fact O. it curls up into many loops.. resembling in shape and dimensions F. at one time undulating. West Africa. and its breadth about 1/2000 inch. the latter apparently being a mistranscription of "volvulus" (from the Lati n "volvo volvere" = to roll or turn round ). but informed Patrick Manson in a personal communication 82. and with the exception of the abruptly pointed tail the filaria is of nearly equal breadth throughout its entire length.. Both tumours contained several female and male worms. each about the size of a pigeon's eggs. volvulus or blood-borne embryos of another species which had contaminated the ski n biospsies is uncertain. At the head. two small dots are noticed.. Leuckart had also sent Manson an histological section containing a fragment of the uterus of one of the worms. Brazil. was imprecise and does not necessarily indicate the same affliction as that described by O'Neill. the forme r being about 6-70 mm in length and the latter about half that size. with due to acknowledgem ent to Leuckart. then. measuring it now we find its length about 1/100 inch. Leuckart did not publish news of this discovery. and now twisted as if into an inexplicable knot. they wer e coiled together to form a ball which was very difficult to unravel. of course. but was presumably intended to draw attention to the twisted and coiled intertwining of the worms. but their nature could not be determined. or blunted extremity. removed two tumours. in a chapter he wrote on skin diseases in the tropics for Davidson's book Hygiene and disease o f warm climates89. DISCOVERY OF THE ADULT WORM The discovery and publication of the finding of the adult O. It was left to Manson to publish a skimpy notice of the parasite. whether this was Leuckart's or Manson designation was not indicated in the text. then a case could be made for designating the worm now known as Onchocerca volvulus as Onchocerca dermathemica . Nevertheless. This mass of worms was situated in a cavity which contained fluid laden with embryos . compared to these parasites. The section on this parasite was labelled Filaria volvulxus. the embryo of . an unnamed German doctor working in the Gold Coast (Ghana). if they were. This patient had been troubled wit h recurrent attacks of a skin complaint. This term. having rapidly untwined itself. one from the scalp and the other from the chest. he found that the y contained worms and sent them to Rudolf Leuckart in Germany for identification. Manson remarked: It was stuffed with outstretched embryos. nocturna.662 were often seen: A History of Human Helminthology Thread-like in form. also labelled "craw-craw". On examining the specimens. da Silva Araujo recovered from th e skin of this patient microfilariae which he named Filaria dermathemica 129. from two of the local inhabitants. Possibly. 102 It is possible that the same parasites were also seen in 1875 by Dr da Silva Araujo in a negro in Bahia. diurna and F. Manson concluded that these worms were not the parental forms of microfilaria diurna (i. Labadie-Lagrave and Deguy described a youn g female worm found in a nodule removed from a French soldier who had been on an expedition to Dahomey in West Africa. On making an incision. Eventually. running along shallow tunnels. Owing to this and the softness and brittleness of the worm. This was composed of granular material. 89 On the basis of the absence of a sheath. which could be easily scraped off. District Surgeon in Sierra Leone. they called the parasite F. Prout examined the blood and aspirates from a lymph node of th e second of these patients. caseous-looking material. These two worms formed the whole contents of the cyst. Concerning the tumour. Professor Leuckart makes the same remark.Onchocerciasis 663 F. made in recent years in African pathology and helminthology. and re-entering the cyst. Filaria volvulus seems to have been comparatively ignored. He made no mention of the micro-filaria e discovered in skin by O'Neill nearly 20 years earlier. he concluded: beyond the facts just stated. and more abruptly truncated at the cephalic end. entering the cyst wall. on microscopical examination. and may well have been unaware of the report. In 1901 Prout described the worms recovered from tumour s removed from two frontier policemen by Dr Hood.. was found to contain numerous filarial embryos. volvulxus. flat nucleated epithelial cells. nocturna I did not see represented in the embryo of F... however.. and were certainly not the mature W. lying in loops twisted up in the most confusing fashion. This. Parsons had in fact seen five patients and wrote: very little was known or taught of this particular nematode when (in 1903). notwithstanding very limited opportunities. I succeeded in isolating a complete unbroken adult male. and also somewhat broader proportionately. he wrote: The tumour was about 1 in.One important feature of F. in breadth.. viz. From the numerous discoveries. diurna and F. Somewhat wistfully. however. The capsule of the cyst consisted of dense fibrous tissue. loa). volvulus 78. lined internally by a layer of soft. we possess very little information on the subject. Further examples of onchocercal infection with recovery of adult worms were reported by Brumpt (1904) 25. bancrofti. and contained free embryos. a greenish. semipurulent-looking fluid about the consistency of cream escaped from the cyst. that this Filaria is far more common in certain parts of Africa than is generally . the sheath.108 Prout then went on to give the first detailed description of the male and female adult worms. and I found it impossible to do so without breaking it. Fülleborn (1908) 52 and Parsons (1908) 107. and described t he microfilariae. While other members of the Filaridae have received a good deal of attention during the present decade.. in length by about 3/4 in. and the head. volvulxus was somewhat shorter.89 Six years later (1899). it was a matter of the greatest difficulty to dissect it out.I became a government official in Northern Nigeria. I am inclined to think. Observations on this and allied matters are very much wanted.e.. it is evident that many novelties await the investigator of diseases in that country. The interior of the cyst was filled with adult filariae. tail and intermediate fragments of a female. but was unable to find any microfilariae. decided that it was a different species which h e named O. but the article was republished in French in 1919 115. showed that there were considerable variations among the specimens and that no consistent differences existed between the American and African forms of the worm. after a laborious effort. caecutiens to indicate that the parasite caused blindness (from the Latin "caecus" = blind) 26. Although he thought that the worm resembled O.. Extremely fragile.664 supposed. I extracted a whole piece that measured almost 30 cm (sic). His discovery was first reported in a newspaper. Fülleborn believed that O. after careful examination of numerous adult filariae removed from the tumours. An editorial in the British Medical Journal in 1935 describing the latter's work. volvulus. Calderón 34 concurred with this opinion. on 29 December 1916. caecutiens is merely a synomym of O. a conclusion which means that the name O. it broke at the slightest pull. a parasite of the horse.. I was unable to identify the parasite fully. The name Onchocerca was derived from a combination of the Greek words (ONCHOS) meaning "hook" and (KERKOS. reticulata.. volvulus and O..114 Subsequently. however. with the characteristics of a filaria. white and ball-shaped. Robles removed other cysts and obtained isolated worms b y digesting them in a dog's stomach for five hours. In 1916. that the Central American form does not differ in any way from the long-known type from the old world.The thick cuticle and the very obvious transverse striations made me think it was of the genus Onchocerca. donkey and mule i n Europe42.. then the formal description appeared in La Juventud Médica in 1917114. however. but considered that there were differences in the clinical manifestations caused by the two parasites 54.. In an accompanying article. La Republica. or a male. undertaken as part of the Harvard Department of Tropical Medicine expedition to Guatemala. However. and after comparing it with the specimens collected by him in the Congo. CERCOS) meaning "tail". Railliet and Henry111 transferred the worm from the genus Filaria of Müller98 to the genus Onchocerca which had been erected by Diesing i n 1841 to house O. volvulus. not having the head.55. he thought that some characteristics did no t coincide exactly. Subsequent studies by Sandground 125 in which more material was examined.The dissection of the parasite was extremely difficult because it seemed to be sewn into the tumor itself. caecutiens were morphologically indistinguishable. accepted this opinion: Another important result of the expedition has been the final decision. Brumpt gave a detailed description of the parasite.107 A History of Human Helminthology In 1910. Rodolfo Robles in Guatemala removed a tumour from the forehead of a boy and on opening it found that it contained: a fine worm. the tail. Most of the copies of the issue were destroyed in an earthquake.3 CORRELATION OF O'NEILL'S MICROFILARIA WITH THE ADULT . This provided an opportunity for examining a large number of patients with onchocerciasis . volvulus and the parasite described by O'Neill. volvulus infections were very common (as were Loa loa and Mansonella perstans. but Wuchereria bancrofti was absent). none of the other microfilariae which may be found in human s (Loa loa. He believed that they might be microfilariae of O. Careful measurements of the size an d . French Equatorial Africa.) had at that time been discovered. volvulus so submitted them to Fülleborn who could discern no differences between them and those prepared from O. volvulus in 1901. O. This observation was confirmed when Simon the n obtained lymph nodes from another patient with onchocerciasis who wa s operated upon for a femoral hernia. he found a microfilaria similar to those aspirated from a n onchocercal cyst only once in 200 blood examinations. but failed to speculate on the relationship between O. Prout did not relate these worms to the microfilariae of craw-craw that had been described by O'Neill. VOLVULUS AND ONCHOCERCAL DERMATITIS When O'Neill in 1875 first described microfilariae in the skin of patients with craw-craw. microfilaria nocturna (= bancrofti). he showed that they were all distinct from each other in one respect or another 108. and the parent worm of microfilaria bancrofti was still unknown. When Prout described the morphology of adult O. In 1913. Simon had found large. Mansonella perstans etc. volvulus microfilariae. bancrofti microfilariae 83. volvulus adult worms. O'Neill's omi ssion of any mention of the absence of this sheath in the skin microfilariae that he saw 102 implies that he had not seen Lewis' s paper and may well have bee n unaware of it. microfilaria perstans and the Onchocerca microfilaria. Ouzilleau reported that in the re gion of Mbomu. he also compared in tabular form the salient diagnostic features of microfilaria diurna (= loa). however. Like Manson. Ouzilleau confirmed Prout's observation that microfilariae were not present in the blood. Lewis had de monstrated their presence in the blood only three years earlier. but Ouzilleau was supported later that year by Fülleborn and Simon56. the microfilariae of Wuchereria bancrofti had been discovered only 13 years before. This is not particularly surprising since he was a naval surgeon on the high seas and away from current librar y facilities. Many years were to pass before such a relationship was established definitely. unsheathed microfilariae in the inguinal lymph nodes and in the blood of a patient with large onchocercal nodules on the superior iliac spine. but did find them o n many occasions in lymph node aspirates 103. Furthermore. Leuckart and Manson 89 were the first to recognize this characteristic absence of a sheath in O.Onchocerciasis 665 O. This finding was criticized by Low who felt that they must have been W. The major difference between the microfilaria described by O'Neill and that found by Lewis was the presence of a sheath in the latter's case. Th e microscopical facilities and staining techniques available during that perio d were not advanced sufficiently to permit a detailed description of th e morphology of these parasites. Thes e observations satisfied Low who now wrote: it is at once seen that the embryos found in the lymph glands and blood of the native infected with volvulus cysts correspond with . volvulus were identical. volvulus or a very closely related species. bancrofti and Loa loa. one of which upo n excision yielded a male and female O. Simon also showed that although the blood contained no microfilariae. volvulus. O. it was still not realized that these microfilariae were also found commonly in the integument and were the same as O'Neill's parasites. volvulus. Montpellier and Lacroix in 1920 were first to put forward this view. remarking that craw-craw or filarial itch used in the restricted sense of O'Neill corresponded in geographical distribution with O. except in rare . Systematic examination of these lesions resulted in the discovery of the constant presence of microfilariae in the dermal layer of the skin. Montpellier and colleagues reaffirmed their views in another paper pub lished later that year. moreover. which they called gale filarienne (filarial itch) . and was associated with inguinal lymp hadenopathy and an eosinophilia. volvulus-type microfilariae could be obtained in blood specimens if excessive pressure was applied to the skin. are the same as the real embryos of O. Finally. was a dermal manifestation of onchocerciasis 95. including the use of concentrating techniques. Dubois wrote that microfilaria volvulus was present in inguinal lymph nodes and stated that he had never succeeded in finding them in the blood 43 and Robles in Guatemala only once observed an infection when he pricked skin near a nodule 114. Not to be outdone. flanks and lumbar regions.84 Ouzilleau's views were again confirmed in 1916 by Rodhain and van de n Branden in Leopoldville. They reported that many native troops from Africa complained of a skin affection or itch which was most marked on the buttocks.or one might say. These investigators regarded the condition as identical with the craw-craw described by O'Neill in 1875 and concluded that this condition. Nevertheless. independent of the vascula r system. Montpellier and Lacroix considered the microfilariae to be embryos of O. Further investigation. and later b y Montpellier and colleagues 97.666 A History of Human Helminthology location of various landmarks on the microfilariae proved conclusively that the microfilariae from the lymph nodes and from O. volvulus and reported that. Despite repeated and intensive investigations . however. perhaps squeezing them out in the lymph. Rodhain and van den Branden failed to find any microfilariae in the blood of 29 patients with clinica l onchocerciasis yet were able to find microfilariae in 11 of 28 patients after the single puncture of a femoral or inguina l lymph node 119. At the conclusion of their paper which they presented to La Société d e Pathologie Exotique in France. revealed the presence of fibrous cysts in some patients. by Robles in Guatemala. Similarly. Brumpt challenged Montpellier and Lacroix's proposition on the grounds that the distribution of craw-craw an d onchocerciasis were different27. Belgian Congo (Zaire) and by Dubois in the Well e (Uele) district of the same country. and were different from those of W. In fact . all their patients with filarial itch had onchocercal tumours. In the following year. . and that all persons with one of these nodules had the eruption characteristic of filarial itch94. cause d itching and scratching which in turn exacerbated the condition. as were the same microfilariae seen in th e skin. ELUCIDATION OF THE MODE OF TRANSMISSION: DISCOVERY OF THE BLACKFLY INTERMEDIATE HOST When Manson first described O. volvulus in the causation of filarial itch was doubtful 28. volvulus. both groups of investigators were probably partly right. Finally. it seemed c ertain in retrospect that the filariae seen in the skin 50 years earlier by O'Neill were indeed O. Ouzilleau and colleagues in the Congo (Brazzaville). Ghana. volvulus microfilariae. but that examination of skin biopsies taken from 50 health y men selected at random revealed larvae in 34% of them.Onchocerciasis 667 instances. with microfilaria e stimulating an inflammatory reaction which. he wrote that "Judging also from the absence of sheath. Manson probably had in mind the likelihood that infection was transmitted by some blood-sucking insect in the same way as he had shown with W. diurna or F. bancrofti. amongst other things. Thus. They found that not only were O. they did not consider that "craw-craw " was connected with onchocerciasis 105. volvulus microfilariae present in the skin of patients with Onchocerca nodules. Thes e investigators examined the skin lesions and concluded that subjects infecte d with O. Th e observations of the French workers were confirmed by Macfie and Corson in Accra. Finally. Nevertheless. it may be that the life history of this parasite is somewha t different in character from that of F. This elicited another response fro m Montpellier and Lacroix 96 who discussed the advisability or otherwise o f retaining the term craw-craw as a dis tinct condition. volvulus adults were indeed derived from that parasite. MacFie and Corson showed at autopsy of three infecte d individuals that parasites were p resent in widely separated areas of the skin but were absent from the mucous membranes and internal organs 86. They reiterated their belief that the skin lesions were due to itching whereas Ouzilleau and colleagues had ascribed the skin reactions directly to the action of the microfilariae. volvulus nodules always had microfilaria volvulus in the dermis. yet unaccountably. despite the reservations of some sceptics such as Brumpt. with five having cutaneous lesions in addition. This failed to convince Brumpt who again asserted that any role for O. by the middle of the 1920's. it was becoming clear that th e unsheathed microfilariae in lymph node aspirates which looked the same a s those obtained from O. nocturna" 89. studied a village in which 16 of the 27 inhabitants were afflicted wit h onchocercal nodules. and that these parasites elicited an inflammatory reaction which caused th e cutaneous lesions. Hipposbosca or a tabanid. The majority rested on the ears. the largest number of ill patients was found. Stegomyia fasciata (= Aedes aegypti) and Mansonia uniformis. Th e exceptions were two flies (which he erronously called mosquitoes): From a careful investigation. cheek and neck with the occasional one on th e . or the copepod (crustacean) Cyclops pallidus with O.500 feet were infected. when he was in Nigeria. sucking blood to the point where you can see the abdomen fill progressively.000 feet. In 1913.000 and 4. calcitans with the human parasite. Robles in Guatemal a. by a masterly series of observations. we deduce that only two mosquitoes of the genus Simulium: the S. Roble s exposed two largely naked children at 10 a. O.they bite for five minutes. incidentally.300 and 2. only those workers who picked coffee by day at heights varying between 2. the leech Hirudo medicinalis. Further.. were never infected.114 On one of the farms where the flies abounded in great numbers. but among the people living at the lower village. Leiper tried to infect the flies Stomoxys nigra and S. exist between 2.000 feet above sea level. dissection at late r dates provided no evidence of i nfection of the flies 81. Breinl in Australia reported that he had been unable to infect Stomoxys calcitrans. the mosquitoes Culex fatigans (= quinquefasciatus). had come very close to the truth as early as 1917.000 feet but not in people living at lower altitudes who drank the same water which had flowed through the infection areas. 86 Macfie and Corson (1922) with the tse-tse fly Glossina palpalis .300 feet. Similar experiments were tried unsuccessfully by a numb er of subsequent investigators: Rodhain and van den Branden (1916) with the mosquito Aedes aegypti and the bedbug Cimex 34 rotundatus 119. the same blood-sucking insects were found above and below 2. he noted that in one farm which had two ranches. or an ixodid tick 85. they become so heavy they can hardly fly. all the inhabitants of the higher site were infected. When they are completely full. they first coined the term onchocerciasis to describe the diseas e caused by infection with Onchocerca).. wh o remained there. In the places where these insects were numerous. samboni and the S. and they were present in considerable numbers at both locations. one situated at 2.668 A History of Human Helminthology When MacFadden and Leiper in 1911 reported on the contamination wit h Onchocerca gibsoni of Australian beef imported into Britain (when . giving them a red coloration. He ruled out transmission o f infection via water by showing that the disease was common in plantation s above 2. and Blanchard and Laigret (1924) with the tick Ornithodorus moubata and the bedbug C. volvulus. Calderón (1920) with lice. and watched the insects bite. they speculated that the vector wa s probably a blood-sucking muscid fly such as Stomoxys. These individuals slept at home at the lower ranch and their wives. mosquitoes and various flies . lectularis 22. He fed them upon the juice of onchocercal nodules and although there was food initially in the stomach contents.. He also observed that with tw o exceptions. In the same year. dinelli. and many times fall to the earth.000 feet (610 metres) and the other at 2.m. gibsoni 24. Meanwhile. Robles did not catch and dissect these flies. this area in cluding nodules near the trochanters. Accordingly. h e observed that the blackfly prophetically named Simulium damnosum was biting viciously and in great numbers near the streams supplying several of th e villages in an endemic area. Auchmeromyia luteola .. In 1925.Onchocerciasis 669 forehead and chest. he submitted two men who were known to have O. abandoned the search temporarily. 780 flies were captured while biting randomly selected boys and 2. 80% of the insects became infected. but he wrote: "I believe I can hypothesize that these are the intermediate hosts. Thereupon. He then inoculated two monkeys with infective larvae. Details of Blacklock's work wer e . and it has not been done" 114. with the result that up to 82% were found harbouring larvae in th e thorax. it is necessary to demonstrate this.. he postulated that any arthropod capable o f transmitting the worms must be able to da mage the skin and dislodge the larvae in its efforts to reach blood. which was in all probability the larva of O. They have altered completely in shape. the first in the flank and the second in the head. volvulus microfilariae in their gut . h e resumed this operation at another vill age. but finding nothing. Wild flies were then fed upon infected persons and kept alive for as long a s possible. began to investigate the mode o f transmission of onchocerciasis in Sierra Leone. but was unsuccessful in transmitting infection. Several moults appear to occur before the form is reached which is capable of invading the head. the Briton. Unfortunately.. Donald Blacklock. 1. in the thorax. When flies were then permitted to bite only on a 4 inch ban d around the patients' body. In 1926. He therefore caught 100 specimens and examined them for larvae in the gut.320 wild Simulium were dissected and 1. one intradermally and the other subcutaneously. Meanwhile.6% of the insects contained larvae morphologically identical with O.they have also lost a great deal of their mobility. At any rate. bu t were not infected with any other filarial parasite. which reinforced his idea that it must be inflicting sever e damage. which was common in the houses. he noticed that the insect was slow in drawing blood. although only one worm was found in the head. Furthermore. this time with success. he undertook a further series of experiments to study the development of filariae within the flies. 20 Blacklock found that when worms reached the proboscis they entered th e labium where they remained coiled up waiting for an opportunity to emerge. They are very active and the majority pass out of the gut within 24 hours and may be found in the posterior part of the thoracic muscles in 48 hours.1% were found to contain developmental forms of som e nematode. but n o signs of the parasite were found. He found that development took about ten days to complete an d summarized his findings: The skin forms taken into the gut of Simulium accumulate at the margin of the blood coagulum lying between this and the gut wall. In December 1923 and January 1924. volvulus microfilariae in their skin. Since the microfilariae were not in the blood but in the skin. to the flies and found that 17% of Simulium contained microfilariae in thei r intestinal tract. he first looked at the Congo floo r maggot. In 1923. volvulus. while the remainder were usually seen ove r bony surfaces or joints. damnosum and onchocerciasis in Uganda 61. Ouzilleau's findings were largely confirmed several years later by Dubois who collected an enormous series of 1. callidum 137. neavei was the vector 69. ochraceum and S. mooseri. volvulus larvae in S. Bequaert (1928) described the insect carrier of O. Earlier (1932). and frontal. S. then Gibbons and Loewenthal investigated S. damnosum was an important vector in the Belgian Congo (Zaire) 16. Hisette had shown that in certain regions of the same country. Giaquinto Mira believed that S. RECOGNITION OF THE CLINICAL FEATURES AND DESCRIPTION OF THE PATHOLOGY SKIN DISEASE Once the adult onchocercal worms were recognized within subcutaneou s nodules. In the Americas. Strong i n Guatemala showed in the next year that S. however. a different distribution . development proceeded only in the latter 71. but epidemiological evidence suggests that the prepatent period i s between three to 18 months. volvulus has not been transmitted experimentally to humans by infected flies. Nevertheless.449 patients. Hoffman in Mexico reported in 1930 that although tw o blackflies. He noted that the cysts. parieta l and occipital regions of the scalp 103. Henrard and Peel 141 in 1945 successfully infected laboratory-bred S. Nearly 80% of the cysts were situated on the lateral aspects of the chest. avidum were all vectors131. The adult worms may live for 15 years and ar e capable of producing microfilariae for up to ten years 113. olecranon. ochraceum was the most important species in view of its preference for biting man 60 then Vargas studied the development of O. knee . only scattered reports describing this condition in one or several patients appear ed during the twenty years following Manson's first description. Blacklock's findings were confirmed by other workers in Africa. which varied in siz e from very small to as large as an apple. greater trochanter. S. it was obvious that these lesions were a cardinal manifestation o f onchocerciasis. Wanson.19 and summarized in the British Medical Journal in 192720. were generally superficial in location. damnosum with O. S. especially the iliac crest. then this was confirmed in 1940 by McMahon in Kenya 87. Eventually. Van den Berghe (1941) showed that S. volvulus. On the other hand. The first person to record a large series of patients wit h nodules was Ouzilleau in 1913. Although the skin could usually be moved over them. ochraceum ingested microfilariae. volvulus in Liberia14. they were often tethered to the underlying muscles or bones. while microfilariae may persist for from 6 months to 3 years 46. mooseri (= callidum) and S. He did f ind. O.670 A History of Human Helminthology published in 192618. Their histological studies of these lesions revealed the presence of microfilaria volvulus in the dermis and subdermal tissues . From time to time. In addition to the papules. O'Neill discoursed on the natural history of the condition: The papules arise singly and at irregular intervals. increase to the size of a pin's head. rapidly enlarging. with the addition of oedema. enlarged dome-like papillae i n lichenoid zones and in pruriginous regions with the addition in the latte r location of blisters and ulceration. Ouzilleau and his colleagues in 1921 recognised thickening of the skin variously described as pseudo-ichthyosis.Onchocerciasis 671 of nodules in the body with 30% being locate d over the trochanters. front of the wrists. endothelial proliferation and fibrosis were noted by subsequen t investigators90. In contrast. In the height of his suffering the patient tears the pustules.. infiltration with mononuclear cells. the original problem being realized only when onchocercae were recovered from the abscess contents 77. volvulus microfilariae in producing other skin lesions. papulo-vesiculo-pustular eruption which was most marked in the clefts of the fingers. and uniting with those in its immediate neighbourhood. and their liberated and dessicated contents produce large and unsightly crusts. and back of th e elbows. vesicles and pustules. the horny layers of skin were thinner than usual and there was a n increase in fibrous tissue with an absence of blood vessels and glands 105. Desoil and Benoit studied the histological appearances of an excise d onchocercal nodule and found a granulomatous inflammatory reaction around the adult worms and microfilariae migrating throughout the tissues of th e "tumour"40. 102 It was the itching and consequent scratching which led to the rediscovery b y Montpellier and Lacroix of microfilariae in the tegument 95. This distribution is classical of scabies as he himself remarked.. and appear of the same colour as the surrounding integument. ichthyosi s simplex and lichenization. with very little increase in size.. often with infiltration of the basal layers by leucocytes. Similar findings were then found by many investigators. In some cases. like ringworm. and it may well be that he was dealing with a dua l infection. As has already been recounted. eosinophili c infiltration.In about two days' time the papule becomes converted into the vesicle. the pigment wa s lacking. feel firm to the touch. with the distribution of nodules tending to follow more the pattern described b y Dubois. volvulus to nodules was clear. the papules arrange themselves in a crescentic form. Similar observations. it was not until 1920 that O' Neill's description of filarial worms in craw-craw was exhumed from the librar y archives and equated with O. O'Neil l described craw-craw as an itchy.101. volvulus by Montpellier and Lacroix. and in the course of a couple of days the pustule is developed. 21% on the sides of the thorax and 19% either on different or two or more sites 43. nodules became infected secondarily with bacteria and presented as abscesses. considerabl e controversy surrounded the role of O. 29% on the iliac crests.122. In leucodermic areas. hyperkeratosis of the epidermis. Montpellier and Lacroix 95 did not emphasize the inflammator y .. While the relationship of O. bancrofti was its primary cause44. Variations on these themes were seen in onc hocerciasis in Central America. volvulus. although there was sometimes a layer of definite inflammatory change49. volvulus microfilariae in aspirates from enlarged lymph nodes. volvulus microfilariae in hydrocele fluid 49. Dubois eventually modified his views and concluded that while O. One of the major objections which Brumpt had raised about th e onchocercal nature of these lesions was the frequent absence of onchocerca l nodules. pruritus and poor vision. In 1915. in which a sac of atrophic skin containing sclerosed glands in a matrix of connective tissue and lymph exudate. Another problem which was the subject of some controversy was whether or not onchocercal infection caused elephantiasis. but he did not know the cause. Ouzilleau was supported by Dubois who proved onchocercal infection in over 90% of 53 patients with elephantiasis 43. Ouzilleau returned to this theme i n 1923104. explanations were furnished by th e discovery in autopsies of two humans of clinically occult adult worms whic h were free in the tissues unencumbered by a fibrous. only O. a burning sensation. i. so that the matter is not yet completely resolved. nodular reactions15. W. often with enlarged lymph nodes. Although these criticisms were no longer tenable when man y investigators demonstrated the unequivocal presence of microfilariae identical with those of O. In order to explain the pathogenesis of elephantiasis i n Onchocerca infection. M. was described by Nelson as bein g frequent in persons heavily infected with Onchocerca in Uganda99. Finally. loa being present. On the other hand. Since he had found O. Robles was consulted by a woma n concerning recurrent erysipelas of the face which was accompanied by fever. a form of pseudoelephantiasis called "hangin g groin". Rodhain put forward the hypothesis that obstruction to lymph flow was caused by microfilariae in the lymphatic capillaries 118. then the realization that nodules might be located in the deep. Kirk (1947) found that hydrocele and scrota l elephantiasis were very common in patients with onchocerciasis in the Sudan in an area where bancroftian filariasis was rare 76. there was a condition known as "Erisipela de la Costa" (erysipelas. Afterwards he saw a boy with the same features: . Ouzilleau (1913) had found that up to 3% of the populati on he surveyed had this condition. he suggested that this parasite may be the cause of elephantiasis 103.e. then was echoed by Dyce Sharp who found O. yet Wuchereria bancrofti was absent.672 A History of Human Helminthology reaction. nor did Dyce Sharp who found that microfilariae were not usuall y associated with inflammation. inaccessible tissues. perhaps partly due to the light skin colour of many of the infected persons and the biting habits of the vectors. volvulus favoured the appearance of elephanti asis. volvulus in the skin. Nevertheless. In Guatemala. perstans and L. or became atrophic 65. These differences in severity were probably due t o biopsies being taken from areas of skin with differing severities of disease . Harris summarized the natural history of the skin lesions by remarking that the first skin affection was an itching rash which then either became elephantoid. red skin inflammation of the coast). The swellings persist much longer. with an absolutely typical greenish livid color. up to months in the same stage.114 In the chronic stage. The cheeks were puffed up with shiny. elephantiasis of the ears.. that the adult worms could be long-lived. bent forward with skin wrinkled and scaly. the forehead. which were not usually situated on the head. a lic henoid form. and the superior lip. the nodules ha d perforated the cranium and were resting on the meninges. which are doubled in size. for he found living worms in a cyst which he removed from a patient who had been living out of an endemic area for seven years. papillomatous an d hyperkeratotic62. They were generally situated in the sub cutaneous tissues but were occasionally tethered to underlying structures . Although Robles had commented upon elephantiasis of th e limbs. in four of 500 patients on whom he operated.After three to four days the fever falls slowly and the patient enters a chronic stage. the skin eczematous.. The ears were much increased in size with the external ear pushed forward. Robles observed two forms of skin disease .114 On his forehead was a tumour the size of a cherry. but usually at the end of 20 days they diminish notably.. This is not altogether surprising as the most obvious feature was the presence of nodules. He noted too... dry. Robles collected a large series of patients and noted that the nodules were found most commonly on the head. However. dry and whitish.. tense and warm simulating erysipelas. and an eczematous dermatitis in which the lesions were papulo-vesicular. excoriated.132. red.. it was this nodule tha t Robles excised and first discovered the adult Onchocerca in the Americas and later remarked: "I understood then that the 'erysipelas' lesions surely were due to the presence of this parasite" 114. A few years late. the edema was hard leaving no digital impression. the typical greenish color suggests the diagnosis instantaneously. scaly. When touched. Some patients developed acute inflammation in which the skin became: smoothy. however.Onchocerciasis 673 There was edema of the eyelids. scaly lesions that resembled chronic eczema. EYE DISEASE The early investigators of onchocerciasis in Africa made no mention at all of eye disease.On the limbs of the body there is a uniform swelling with induration as seen in the elephantiasis of the Arabs. the lobe was edematous. pigmented and lustrous. Indeed. Bein g . shiny. Goldman and Ortiz classified the dermatitis into three forms : pigmentation dermatitis or "mal de morado" (= purple disease) in which th e skin became purplish in colour. Apart from the skin nodules.114 Robles observations were confirmed by Calderón 34 and by Strong 131. also there was a greenish coloration of both cheeks as you would see in ecchymosis of several days' duration. he wrote that when the face was involved: the cheeks are always indurated. subsequent investigat ors were agreed that this condition was very rarely seen in American onchocerciasis. for days. a dull iris with a deformed and constricted pupil.106 Pachecho Luna never saw any microfilariae in the eye itself. might have sensitized them to look for other manifestations of illness caused by microfilariae. it is presumed that all the symptoms are due to the secretion from a parasite in the human organism. Finally. the patients often complained of an associated eye trouble. the clinical presentation t o Robles in Guatemala was completely different. 114 As with the skin disease. The boy complained of cloudy vision. at midday he experienced burning and pruritis (sic) in the eyes which felt as though they were full of sand. it is doubtful if any of the m even had a simple ophthalmoscope. the usually brilliant and transparent corneas were now dull and without glossiness. Robles found photophobia. In contrast. but remarked that examination of the fundus by Dr Pachecho Luna had not revealed any abnormality of that part of the eye. and ophthalmic symptoms and signs were marked in the boy from whom he first recovered an adul t Onchocerca: The ocular symptoms consisted of redness of the conjunctiva and iritis. Robles' first. they were more concerned with th e possibility of the organism causing elephantiasis. In chronic cases.. patient complained o f losing her sight. pte rygia. The clouding of his vision had disappeared so that now he could see perfectly. and progressive loss of visual acuity . he noted that a dangerous iriti s could complicate the picture. In acute ophthalmic onchocerciasis.and very notable diminution of visual acuity. they were not aware of onchocercal microfilarial skin disease which.674 A History of Human Helminthology aware of microfilariae in lymph nodes. had they known of it . of a toxic substance. pigmentation of the sclera. the pruritis (sic) and gritty sensation were no longer present. he described periorbital pain.. acute o r chronic iritis. they were devoid of the technical equipment necessary for a full recognition of onchocercal eye disease. and wrote that "the cornea has the char acteristics of a punctate keratitis" 114. there were scattered small leucomas as if the patient had suffered from an ulcerative keratitis. and considerabl e . Nodules were common on the head and produced a distinctive sk in disease. sensations of having foreign bodies in the eyes. Furthermore. the light did not bother him any longer..114 What really convinced Robles of the relationship between the eye disease and infection was the remarkable resolution following removal of onchocerca l nodules from his forehead: the child's appearance the following day was completely different. photophobia. corneal leucoma. Photophobia was so intense that the little boy always walked with the brim of the hat pulled down to shade his eyes from the light. there were periorbital pains. the edema as well as redness of the conjunctiva had disappeared. Further. These features were echoed by Pachecho Luna who thought that the punctate keratitis was due to a microfilarial toxin as eyesight improved rapidly whe n nodules were removed: For this reason. Calderón commented upon punctate keratitis. . Further. often located on the face. Similarly . Robles recognized two forms of eye involvement. which produces at times appreciable lesions in the eyes. punctate keratitis. bu t undiagnosed. but h e provided statistical and epidemiological evidence to support his thesis 29. It was not until 1931 that Hisette reported that in a focus of onchocerciasis in the Belgian Congo (Zaire). Whereas the first condition wa s clearly due to Onchocerca infection. however. in addition to a description of anterior eye disease. he found that removal of the nodule s often ameliorated the symptoms 68. who together with Zschukke. and many author s confirmed the relationship between O. In the same year. but most people were blind because of a gross choroidoretinitis with optic atrophy.80. with nearly half of them being blind or nearl y blind. Blacklock in 192 7 reported that he could find no evidence of eye disease in patients wit h onchocerciasis in Sierra Leone 20. The first persons to mention onchocerciasis of the eye in Africa wer e Ouzilleau and his colleagues who recorded that one of the 16 infected persons they had found in a village of 27 inhabitants had keratitis 105. His findings prompted renewed efforts to find ocular complications o f onchocerciasis in other parts of Africa and in 1935 Bryant reported tha t blindness was appallingly common in a part of the Sudan where the infection was endemic. The disease differed from onchocerciasis as generally described in Africa in that large numbers of cysts were located on the head. Puig Solanes and his colleagues in Mexico came to the sam e conclusion 109. for microfilariae could not be found in histologically-sectioned eyes. Further. Publication of the observations in Central America stimulated a search for eye disease in African onchocerciasis but it seemed to be largely absent. . volvulus infection and eye disease 36. thus. there was some doubt about the second. He concluded on the basis of slit lamp examinations and a review of the literature of the pathology of the disease that living microfilariae caused n o tissue reaction but that the lesions were a response to dead microfilariae 112. although there was no erysipelas-like lesions. althoug h such statements were criticiz ed by Guerrero (1922) on the ground that patients were not followed up to see if the problems recurred and he contended that a "post hoc propter hoc" interpretation of the relationship could be fallacious 64. In 1945. His view did not endure. Doubts were also expressed by Fülleborn. 20% of the patients with onchocerciasis were blind and that 50% of the population suffered from eye troubles. Hisette amplified his findings in a long paper published in the following year where. Some of this was due to anterior eye disease with onchocerca l punctate keratitis and corneal sclerosis. A number of other authors also remarked upon th e rapid disappearance of acute symptoms after removal of a nodule.Onchocerciasis 675 impairment of vision34. he drew attention to an association with choroidoretinitis 69. found nodules in 70% of labourers on one Guatemala plantation yet found objective evidence of diminution of vision in only two.55. Ridley showed that slightly more than one third of patients wit h onchocerciasis in a region of the Gold Coast (Ghana) had evidence of eithe r anterior or posterior disease. He concluded that the carriers of Onchocerca that they had seen were perfectly healthy individuals and h e deprecated the prophylactic removal of parasitic cysts which had bee n proposed recently54. iritis mor e rarely). Strong and his colleagues indicated that in a study of 11 eyes removed at operation. Choyc e (1958) considered that there was no good evidence that posterior lesion s (retinal degeneration and optic atrophy) were due to onchocerciasis and. Giaquinto Mira in 1934 also described microfilariae in the optic nerve 59 then in the same year.. did not often lead to more than a slight interference with vision 38.676 A History of Human Helminthology Histological studies of infected eyes were slow in coming because o f difficulties in obtaining material. While the vast majority of observers accepted that onchocercal infectio n could cause devastating eye disease. In reviewing this opinion. believed that the anterior diseas e (keratitis commonly. on the distribution and density of microfilariae in the body. microfilariae could be found throughout the anterior eye. the ciliary body inflamed and fibrotic. volvulus infection. Woodruff and his colleagues therefore investigated the questio n further in Uganda and concluded that many other factors than the mer e . a commentator in The Lancet wrote: "If this is correct. Most investigators have agreed that whether or not eye disease is likely to occur depends. microfilariae were found in the cornea. there is little to justify the growing reputation of onchocerciasis as a blinding affection"4. Silva (1932) found microfilariae in the choroid and posterior two thirds of the cornea in sections of eyes128 and Hisette in the same year found microfilariae throughout the eye 69.the incidence of blindness due to choroido-retinal lesions amongst infected persons is only six times higher. In 1928 and again in 1930. and eye lesions with blindness: The occurrence of anterior segment lesions is related to the presence of microfilariae in the anterior chamber and the head region consequent upon a spread of microfilariae from the lower parts of the body.. on the basis of his experience in the Cameroons. is 23 times higher in these heavily infected communities than in lightly infected ones. They showed that there was a clear relationship between heavy microfilarial counts in the skin.. ciliary body and choroid132. th e cornea was vascularized. This spread is associated with a high intensity of infection in the human host and this in turn probably reflects the duration and intensity of the exposure to which the host has been subjected throughout his life. microfil ariae were seen particularly in the outer one third of the cornea and in the optic nerve 100. Kershaw and his colleagues working in Africa described in 1954 a technique for quantifying the microfilarial density in various parts of the body. Ochoteren a described the findings in an eye excised from a blind man.. when expressed as a percentage of infected persons. 75 These observations were then confirmed by Rodger and Brown 116. although admittedly due to O. particularly of the upper parts of the body. there were still some sceptics. at least in part. and the sclera and choroid were infiltrated with plasma cells although he could no t demonstrate microfilariae therein 29... The eye was fixed entire and serial sections made.Blindness due to anterior-segment lesions. It was realized e arly that the propensity of flies in Central America to bite near the head and for nodules to form there increased the relativ e frequency of eye disease in that region compared with Africa. Bryant (1935) then showed that in patients with anterio r onchocerciasis. iris. . Another way of demonstrating the presence of microfilariae was described by O'Neill in 1875 but was forgotten until the technique was resurrected b y Montpellier and Lacroix in 1920. which will remove the base of the papule and the cutis vera. Microfilariae may also be aspirated from draining lymph nodes as was shown by Ouzilleau 103. and in expatriates in Britain. The most obvious of these is excision of the nodule an d finding the adult worms therein. from observations of a large series of patients . On the other hand. that a reviewer in The Lancet in 1963 wrote: The relation between infection with these worms and damage to the eyes is by no means straightforward. as was done in Africa by the medica l missionary who sent the original specimens to Leuckart. now take another slice.. At this point. Blindness is likelier to be due to lesions in the posterior part of the eye. and by Robles i n Central America. This view is now generally accepted. posterior lesions being rare. but such lesions rarely cause complete blindness. and magnified about 100 diameters. concluded that both anterior and posterior regions of the eye were involved in a typical sequence of inflammatory processes caused by the microfilariae 110. so that the papule will be the highest point. DEVELOPMENT OF DIAGNOSTIC METHODS The diagnosis of onchocerciasis can be established by finding the parasite in a number of ways.Onchocerciasis 677 presence of microfilariae were necessary for the production of eye disease 142. He now concluded that in American onchocerciasis blindness was due to anterior lesions. Alternatively. moistened with a drop of water. a few larvae but no eggs in 30%. which may be discarded. will very likely contain at least one filaria. so much uncertainty and controversy surrounded the question of onchocercal eye disease. This film.5 Choyce in 1964 then compared the ocular manifestations of onchocerciasis in endemic areas in Central America.. then with a very sharp scalpel slice off the epidermis. Van den Berghe used this technique in a large series of 405 nodules and found eggs liberated by damage to the female worm by th e needle in 60%.Everyone agrees that microfilariae invading the cornea may cause conjunctivitis and keratitis. Choyce still held that the posterior eye lesions were due to other factors such as vitamin B deficiency or inheritance 39. easily detected in the field by its violent contortions. and neither eggs nor larvae in the remaining 10% 17. Nevertheless. both punctate and sclerosing. a nod ule can be aspirated with a needle and the contents examined 103. Quere and his colleagues in Africa. while in the African form of the disease choroidoretinal lesions were present as well as anterior eye involvement . in Africa. but opinions differ as to whether such lesions are really caused by microfilariae or whether they arise from genetic effects and excessive inbreeding. 102 Fülleborn and Simon then showed that the diagnostic morphological features . O'Neill wrote: I find the readiest way to procure the filaria is to take between the finger and thumb a fold of the skin. . but this was clearly a nonspecific finding. Many attempt s were therefore made to develop more specific immumoassays.678 A History of Human Helminthology of O. but this method clearly has its disadvantages and dangers 29. refringent body with a golden reflection which he believed was a filaria in the vitreous. merely by illuminating the fundus with a flat mirror. volvulus antigen preparation but found them in only 18% of patients 119. A number of observers noted that blood eosinophil levels were increased in onchocerciasis. Greater specificity was claimed by van Hoof usin g O. with the Gullstrand ophthalmoscope he saw its shadow on the retinal surface 128. Mazzotti in 1948 drew attention to the fact that a presumptiv e diagnosis of onchocerciasis could be made if pruritus with or without a ras h appeared following the administration of diethylcarbamazine (the Mazzott i reaction ... Finally.see section on treatment) for this was almost invariable i n onchocerciasis but was absent in filariasis 91... 23 In the same year.. volvulus antigen prepared in a different manner in an assay to detec t complement fixing antibodies 72. Rodhain together with Dubois described a skin test using a similar antigen but found cross-reactivity with other nematodes 120. Silva in 1925. Subsequently. Rodhain and van den Branden in 1916 looked for complement fixing antibodies using a n O.is about a third of a millimetre. Bryant reported that microfilariae could be found in aqueous fluid obtained by puncture of the anterior chamber under local anaesthetic with a syringe.. Fifteen years later. The latter described his slit lamp findings: prolonged examination revealed many of these organisms. though I think a better description of their movements would be to say that they tied themselves into knots and untied themselves with amazing rapidity. . then reported the same phenomenon with Fairley's preparation of Dirofilaria immitis antigen121. Torres Estrada compared vari ous means of visualizing microfilariae in the eye with different types of ophthalmic equipment and emphasized that the parasite seemed to be more abundant in the vitreous than in the anterio r chamber and could be seen in the former site early in the disease 134. volvulus microfilariae could be demonstrated by staining them wit h Romanowsky stains 56...The manner in which they propelled themselves through the aqueous immediately suggested to my mind the well-known antics of the mosquito larvae. The presence of microfilariae in the eye can be discerned in a number o f ways. Torroella first used the slit lamp an d saw microfilariae migrating along the corneal surface and moving in a spira l fashion through the anterior chamber 135. Torroella's observations wer e confirmed in 1932 in the Congo (Zaire) by Hisette 69 and also in Uganda by Boase (1935). A few years later. saw a very mobile.their length. The usefulness of this phenomenon was then emphasized by Burch 32. Mazzotti had earlier noted that allergic attacks with fever and local induration of the skin may occur in onchocerciasis. but its feasibility depended upon th e availability of facilities and the number and locations of the nodules to b e removed. then found that such reactions wer e commonly precipitated by the administration of diethylcarbamazine. van Hoof and his colleagues took up the further investigation of suramin which had first been u sed in the treatment of trypanosomiasis in 1921. in a single case and claimed excellen t results49.31. th e severity of the reaction being dependent upon the intensity of infection 91.66.A. This was followed by th e observation of Mazzotti that although the numbers of skin microfilaria e decreased initially. The first results were reported in 1948 by Mazzotti and Hewitt who found some reduction in the numbers of microfilariae in the skin. Many attempts have been made to improve the medical therapy o f onchocerciasis since O'Neill first tried sulphur (which was often useful i n scabies) and found it ineffective. These effects. The surgical excision of nodules containing adul t worms was shown to be effective 69. He also noted that "the nostrums of the native 'medical man' have frequently failed to bring relief after six months ' application"102. nodules extirpated subsequently still contained living adult worms and microfilariae 93. they often increased again a few months later 92. Dyce Sharp (1926) tried a Bayer preparation. Ruiz Reyes tried the same drug bu t without appreciable benefit 123.B. They gave 1 gram a week for seven to ten weeks and considered that it wa s always successful73. In 1947. At around the same time as these re sults were reported. Hawking and Laurie described it graphically.33.45. Enzer (1942) in a preliminary paper investiga ted euflavine.114. i. diethylcarbamazine was introduced for the treatment of filariasis (see chapter 24) then was soo n tried in onchocerciasis. but in contrast to when suramin was used. The same might be said for the modern medical man whos e therapeutic armamentarium is not that much m ore effective. a failure to kill adult Onchocerca and only a transient reduction in microfilarial numbers were confirmed by many investigators 8.e.138. B1916. tryparsemide (arsenic) and suramin (the latter two being anti-trypanosomal compounds) and thought that they may be of some value if combined with protein shock (T. even when small doses of the drug were given: even a single dose of 50 mg hetrazan citrate almost always produced a violent .) therapy 50.Onchocerciasis 679 THE SEARCH FOR EFFECTIVE TREATMENT The management of onchocerciasis has been approached from both surgica l and medical standpoints. Certain antimony compounds and plasmochin were found to have an effect on microfilariae but were discarded as they had no action on the adul t worms which rapidly replenished the supply of microfilariae 1. On the other hand. This phenomenon came to be known as the Mazzotti reaction. Burch tried suramin with some success bu t experienced troublesome side-effects 31 then Ashburn and colleagues showed that suramin had a definite lethal effect on adult worms 8. 79. but these efforts have bee n unrewarding.. even though it kills adult worms.63. sufficient brains.. volvulus without producing a microfilaricidal reaction. patience. Sometimes there was a thick papular rash over the trunk and limbs. Attempts have bee n made to improve the effectiveness of the latter drug. especially of the buttocks and thighs. b y administering the drug in a skin lotion 6. which: Given adequate funds. especially on the kidneys. while diethylcarbamazine suffers from th e twin disadvantages of having only a transitory effect and producing unpleasant side-effects associated with killing of the microfilariae. The United Nations Development Fund/World Bank/World Health Organization Spec ial Programme for Research and Training in Tropical Diseases has set in train a programme to develop new filaricidal drugs effective against O. particularly those whose eyes are at risk.126. a macrocyclic lactone derived from a new species of actinomycete.. oedema and tenderness of the skin. In 1978. Ivermectin was shown to be superior to diethylcarbamazine in both safety and efficacy. Subsequent double-blind studies in West Africa have compared ivermectin with diethylcarbamazine and placebo in patients wit h high skin microfilarial density. DEC-C (diethylcarbamazine citrate) and suramin whose actions were discovered more than 30 years ago and which are far from satisfactory in use. wit h skin microfilarial levels 12 months after treatment being 2-10% o f pre-treatment levels compared with a value of 10-45% for patients treated with diethylcarbamazine 9. most of whom had ocular involvement .What is now needed above all is a non-toxic drug. and some luck. which has a convenient dosage schedule and which can kill or permanently sterilise the adult worms of O. Sometimes the prepuce. .. had exceptional potency against the nematodes Ancylostoma caninum 21 and Dirofilaria immitis 35. 66 The initial encouraging reports with suramin and with diethylcarbamazine were followed by comparative trials 33 and with the combination of the tw o drugs37. Intense itching was always widespread.. Although each drug has had its advocates. Aziz and his colleagues showed that the density of skin microfilari ae was greatly reduced in Senegalese patients treated with ivermectin 12.. Duke in 1981 summarized the difficulties: The outstanding problem in onchocerciasis remains in the treatment of patients. for example. penis and scrotum were swollen..may pay off within the next 10-15 years developing a new drug to improve the prospects of treatment of those threatened with or suffering from ocular onchocerciasis. We are still dependent upon two drugs. Blair and Campbell had reported that ivermectin. The lymph-glands were generally enlarged and tender. suramin has largely been abandoned because of its occasional severe toxicity.680 A History of Human Helminthology reaction which was well marked in 16 hours.. ivermectin resulted in a more sustained microfilaricidal effect. In 1982. 48 While these words were being written. a promising drug was bein g developed.There was always pyrexia. There was usually swelling. volvulus.48 Duke then remarked that towards this end. Streptomyces avermitilis. it is hoped. Like Robles. Blacklock observed that they took from one to five minutes to feed then became so distended that they had difficulty in flying 20. with the frequency varying from one location to another. He demonstrated that the flies were present in the bush in th e vicinity of water. usually from the waist downwards. Wanson and Henrard. particularly smaller waterways. Robles in Guatemala had earlier described some aspects of the biting behaviour of Simulium in Guatemala. up to 100% of the population was infected. damnosum: It is a hilly region drained by several large rivers and a multiplicity of small streams. and that the adul t females lived for about three weeks 140. Both Dubois43 and Rodhain117 in the early part of this century noted that the distribution of onchocerciasis was very p atchy. swampy areas produced by silting up and overflow of the streams are numerous and biting insects are plentiful. Similar terrain was present in the Konno district of Sierra Leone where Blacklock first demonstrated transmission by S. Thus. the frequency of infection was observed to rise with increasing age. McMahon reported in 1940 that S. Each village has in its immediate vicinity several streams. also in that country. In West Africa. 20 This association was explained when the vector was discovered and its breeding habits discerned. but eye disease was much less common in the latter location. neavei was the vector 87 then he and van Someren showed that the larva of this specie s developed on the carapace of a freshwater crab 130. plants and various other impedimenta submerged in fast-moving water. They found that breeding took place in these rivers. They determined that the period for development from egg to adult took about nine days. Duke and his colleagues then showed that this difference may be due to the presence of . later showed that female worms commonly migrated several miles (even up to 45 miles) along rapidly flowing sections of rivers. Ouzilleau found that the infection was common around the headwaters of the Ubangi 103. In East Africa (Kenya). the hills are in most cases clothed with dense bush right to the summit. that female flies bit by da y. and preferred shade and humidity. with larvae and pupae attached to submerged stones. Similar observations were made by van den Berghe in the Congo16. Studies of the behaviour of simuliid flies in Central America gave broadly similar results. he began to study it s behaviour. Dubois observed onchocerciasis around waterways in the lower Welle (Uele ) district43 and Rodhain showed that the condition was prevalent along other tributaries of the Congo117. In general. onchocerciasis wa s present in parts of both the northern arid savannah and in the southern rai n forest. damnosum was the intermediate host. Subsequent studies showed that in some regions. After Blackloc k proved that S. showing that those species preferred to bite by day and around the head (see earlier).Onchocerciasis 681 UNDERSTANDING THE EPIDEMIOLOGY Early workers in Africa observed an association between onchocerciasi s and rivers. This. volvulus was accepted. greatly reduced fly numbers30. as has already been recounted. This idea wa s supported by Diaz who found a small number of pre-Columbian skulls wit h erosions and perforations which he attributed to onchocercal nodules 41. Interestingly. they were concerned only with skin disease and made thi s judgement without any consideration of the ophthalmic complications of th e infection. The alternative hypothesis is that onchocerciasis i s autochthonous to the Americas. Although natural infections with O. A few years later. Fülleborn suggested that onchocerciasis may also be present in Mexico 53. as are the various examples of earl y Spanish literature citing regions where blindness was common. caecutiens was different to O. with the discovery in 1941 . In 1923. however. of course. The infection was first described in Guatemala. however. Torroella considered that the infection may have been introduced into Mexico by a battalion of Sudanese troops sent to assist the French invasion troops of Napoleon III in 1862 136. bu t suggested that trapping may prove feasible 61. remarking that it was futile to attempt to attack the flies in their breeding grounds. This seeme d quite tenable when Brumpt's view that O. The outlook was changed drastically. They were not sanguine about the prospects. In many parts of Central America. they wrote that since huge tracts of extremely fertile country had been rendered uninhabitable through the ravages of Simulium flies. Two hypotheses have been promulgated concerning the origins of onchocerciasis in America 70. then this was confirmed by Larumbe80 . that have been quoted by Figueroa Marroquin in support of this latter thesis 51. there is no evidence that they are a significant reservoir of zoonotic onchocerciasis. The most obvious source of such infection is among the negro slaves carried from West Africa124. volvulus have been found in the gorilla in the Congo and in the spider monkey in Me xico. The first postulates that the infection did not exist in the Western Hemisphere prior to its introduction by infected persons from Africa. was a non-specific finding. together with removal of surrounding undergrowth. but other suggestions have been made. onchocerciasis is often associated with the growing of coffee. THE EVOLUTION OF PREVENTIVE AND CONTROL MEASURES When Gibbins and Loewenthal reported their own studies of onchocerciasis in Uganda in 1933. Subsequently. Buckley found in Kenya that discriminative clearing of bush along the banks of two infected rivers. For example . the question of suppression of these insects was urgent .682 A History of Human Helminthology different strains of both parasite and vector in those two regions 47. and as the lives of those still living there had been made miserable by irritation from their bites. foci of infection were reported in other parts of northern South America. They app lied emulsions of DDT in oil and water at 10-14 day intervals for six to seven months and succeeded in eradicating the flies57. DDT . Ghana. Mass campaigns for the removal of head nodule s have been mounted with a considerable reduction in microfilarial density . Niger and Togo) with a popul ation of ten million people. it is thus hoped to prevent reintroduction of th e disease into treated areas by migratory blackflies and provide protection to an additional eight million people 7. Since 1974. has been applied from the air repeatedly to 14. and will be extended westwards into Guinea. In 1967. naevei bred in limited stretches of two rivers. at an estimated cost of US $133 million. the biodegradable organophosphate insecticide . Eighteen years after eradication of the flies. damnosum out of the control area for 10-15 years.Onchocerciasis 683 by Müller and his team at Geigy in Switzerland of the insecticide. Garnham and McMahon in 1949 used this ne w chemical to attack the fly in one of the three areas in Kenya endemic for onchocerciasis where S.000 km of river s covering an area of nearly one million square kilometres and encompassin g seven countries (Benin. In contrast to the experience in Africa. the breeding places of Simulium in Central America are largely inaccessible and McMahon concluded that control by larviciding was difficult 88. Burkina Faso [Upper V olta]. Roberts and colleague s reported that all the adult O. This programme was based upon the premise that by keeping S. A similar result was obtained following a campaign of sprayin g vegetation along the river banks with DDT from the air in the Congo 139. He concluded that larviciding was th e most efficient means of control and indicated that intermittent control of S. Seven years later they reported that the flies were still absent and that although transmission of onchocerciasis had ceased.133. An alternative approach which has been tried in both Africa and th e Americas has been the repeated administration of diethylcarbamazine. however. this has met with little success because the frequency of side-effects has ensured poor . transmission will be interrupted for long enough for th e infection to die out. The initial two phases of the Onchocerciasis Contro l Programme carried out between 1974 and 1985 cost US $162 million. Ivory Coast. morbidity and onchocercal transmission 131. temephos. the United Nations Development Programme and the World Bank to embark upon a multi-million dollar programme in the Volt a River Basin of West Africa with the objective of eradicating blackflies wit h larvicides. Senegal and Sierra Leone. volvulus had disappeared by about the sixteenth year113. A third phase. McMahon reviewed the information available about the control o f Simulium vectors of onchocerciasis. Mali. naevei had been eradicated from Kenya and parts of Uganda 88. the disease still lingered on58. is to be undertaken betwee n 1986 and 1991. Guinea-Bissau. These results encouraged the World Health Organization in collaboration with the Food and Agriculture Organization. A different approach has been taken in that area for many years. damnosum had been achieved in various parts of West Africa and that S. BEAVER PC. MEEROVITCH E. 1949 9. ALI-KHAN Z. Parasitology Today 2: 233-235. ADAMS AR. 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Universidad Nacional de Mexico 1: 59-62. 1930 OCHOTERENA I. 108. 105. 1919 RODGER FC. Parasitology 1: 359-368. LAR IVIERE M. Universidad Nacional de Mexico 2: 109-115. 115. HENRY AC. DUBOIS A. 1931 O'NEILL J. 1945 ROBERTS JM. 112. Bulletins de la Société de Pathologie Exotique et de ses Filiales 7: 80-88. pp 386-389. 1957 RODHAIN J. 1918 PARSON AC. BROWN AJ. 110. NEUMANN E. 1921 PACHECHO LUNA R.Onchocerciasis 689 101. 11 and 18 years after elimination of the vector. On the presence of a filaria in "craw-craw". Filaria volvulus Leuckart. van den BRANDEN F. LAIGRET. 1908 PROUT WT. La Juventud Médica 17: 97-115. 117. A filaria found in Sierra Leone. Anales del Institut o Biología. ? Filaria volvulus (Leuckart). Antoine . Observations diverses concernant Onchocerca volvulus . Bulletin de la Société Médicale d'Afrique Noire Langue Francaise 8: 1-26. 109. Also. Bulletins de la Société de Pathologie Exotique et de ses Filiales 9: 186-198 . 1963 RAILLIET A. American Journal of Ophthalmology 1: 122-125. pp 58. 1916 RODHAIN J. HIGHTON RB. A contri bution to the study of intradermal reactions in human filariasis. GÖCKEL CW. Assessment of the density of infection with onchocerciasis and the probable level of safety from its ocular complications. Pathogénie de l'éléphantiasis de cette region. 1920 RODHAIN J. Arbeiten über Tropenkrankheiten. 116. Ocular onchocerciasis. 1901 PUIG SOLANES M. British Journal of Ophthalmology. 107. FONTES A. BASSETT M. Transactions of the Royal Society of Tropical Medicine and Hygiene 25 : . Contribución para el conocimiento de la onchocerciasis en Mexico. Recherches diverses sur la Filaria (Onchocerca) volvulus. Transactions of the Royal Society of Tropical Medicine and Hygiene 51: 271-282. 1917. 1928. Contribution a l'étude de l' Onchocerca volvulus . Disturbances of vision in patients harboring certain filaria l tumors. Bulletin of the World Health Organization 37: 195-212. 1945 QUERE MA. Allergie dans la filariose volvulose et la filariose loa. Translated in 74 ROBLES R. 1931 RODHAIN J. Les réactions allergiques qu'elles provoquent et le diagnostic de celles-ci. La Presse Médicale 31: 617-622. Anales del Instituto Biologia. rôle pathogène. Proceso histologico de formación de los fibromas onchocercosos. Les filaires dumaines de la Région du M'Bomou (Afrique équatoriale française). 103. Bulletins de la Société de Pathologie Exotique et de ses Filiales 12: 442-460. 104. 118. 111. BASSETT A. Bulletins de la Société de Pathologie Exotique et de ses Filiales 13: 848-858. Rôle de la Filaria volvulus. Enfermedad nueva en Guatemala. Bulletins de la Société de Pathologie Exotique et de ses Filiales 14: 717-728. 1967 ROBLES R. 106. Revue Belge des Sciences Médicales 3: 613-623. 121. Reforma y Lieja. Obser vations de cas de parasitisme par Onchocerca volvulus chez l'Européen. Monograph Supplement 10. 114. Onchocercose hu maine au Guatémala produisant la cêcité et "l'érysipéle du littoral" (Erisipela de la costa). Onchocerciasis i n Kenya 9. Investigación oftalmológica en la zona oncocercosa de Chiapas. 102. Les filaires de l'Afrique tropic ale. Mexico 2: 69-86. Lancet i: 265-266. British Medical Journal i: 209-211. L'éléphantiasis au C ongo et l'Onchocerca volvulus . 1931 RODHAIN J. 120. DUBOIS A. 113. RAZAFINJATO R. Remarques à l'occasion de la note de M. Festschrift Bernard Nocht. 1875 OUZILLEAU F. Réactions cutanées. Organo de la Secretaria de Salubridad y Asistencia. le Dr. structure and pathologica l effects. 119. 1923 OUZILLEAU. Étude statistique sur la fréquence et la spéc ificité des complications oculaires de l'onchocercose. Sur l'onchocercose au Mexico. pp 49-56. Medicina. Présence d' Onchocerca volvulus dans un abcès suspubien. Contribución al estudio de la onchocercosis de sus manifestiaciones oculares. 1945 141. Recueil des Travaux des Sciences Médicales au Congo Belge 4: 122-138. PEEL E. SANDGROUND JH. Mexico 27: 475-477. 1930 136. 645. LEBIED B. WANSON M. 1934 126. COURTOIS L. Pararticuläres Nematodengranulom (einheimische Onchocerca). TORROELLA JL. 1932 129. Annales de l a Société Belge de Médecine Tropicale 29: 85-89. 1950 131. Southern Medical Journal 25: 113-117. Part II. Ophthalmoscopic observation of microfilariae in the vitreous of patients infected with onchocerciasis. Datos historicos sobre el origen de la onchocercosis en America . Cambridge. 1931 134. JONES DE. Bulletins de la Société de Pathologie Exotique et de ses Filiales 13: 252-254. . pp 234. In. Harvard University Press. Massachussetts. 1952 125. Onchocerciasis. 1932 122. 6. Cambridge. with special reference to the Central American form of the disease. Indices d'infection des simulies aggressives pour l'homme. SARKIES JW. HENRARD C. New England Journal of Medicine 204: 916-920. Memoria sobre a filariose ou a molestia produzida pro um a nova especie de parasita cutanea. Phoretic association between Afronurus and Simulium species. 3. STRONG RP. L'éradication du Simulium damnosu m (Theobald) à Leopoldville. Habitat et comp ortement larvaire du Simulium damnosum Theobald. cycle de développement che z Simulium damnosum Theobald. 1934 133. Onchocerca volvulus Leuckart. Revista Médica Mexicana 32: no. London 166: 350-351. Recueil des Travaux des Sciences Médicales au Congo Belge 4: 113-121 . 1964 137. no. pp 36-86. and the discovery of the early stages of Simulium neavei on fresh-water crabs. 1952 127. BARNLEY GR. with special reference to the Central American form of the disease. RUIZ REYES F. SILVA R. Antrypol in the treatment of onchocerciasis. McMAHON J. 1949 139. 1931 132. WANSON M. Algunas consideraciones sobres el desarrollo de Onchocerca volvulus en los Simulidos. 1945 142. TORRES ESTRADA A. J H Sandground. Harvard University Press. Nature. Bahia. J C Bequaert and M M Ochoa . Massachussetts. como probable origen de la onchocercosis de Mexico y Guatemala. Annales de la Société Belge de Médecine Tropicale 29 : 373-403. 1965 128. American Journal of Ophthalmology 25 : 1445-1448. WANSON M. J C Bequaert and M M Ochoa. Universidad Nacional de Mexico 1: 201-203. Revista del Instituto de Salubridad y Enfermedades Tropicales. Report of progress of th e Harvard expedition. L'Hetrazan dans la période d'invasion de l'onchocercose. ROUBAUD E. Onchocerciasis.690 A History of Human Helminthology 377-382. Bulletin de l'Office International e d'Hygiene Publique 23: 2017-2020. JAMOT E. May-June . In. RUIZ REYES F. vol. by R P Strong. TORROELLA JL. 1920 123. Quelques précisions morphologiques sur l e parasite. WANSON M. VARGAS L. pp 234. Tratamiento experimental en la oncocercosis con el "Naphurid e sodium". Ocular onchocerciasis. McCRAE AW . 1942 138. da SILVA ARAUJO AJ. Mexico 3: 57-65. Anales del Instituto de Biología. HENRARD C. 1942 135. de la TORRE I. WOODRUFF AW. HOOLAND JT. 1949 140. STRONG RP. Salud Publica de Mexico Epoca V. 1947 124. Transactions of the Royal Society of Tropical Medicine and Hygiene 46: 435-436. Schweizerische medizinische Wochenschrift 95: 1102-1104. GÜBLER R. Batallon del ejercito fraces . Part I. van SOMEREN VD. by R P Strong. SIEGENTHALER R. 1875 130. Onchocerca investigations in Guatemala. J H Sandground. Onchocerciasis and the eye in Western Uganda. Landmarks in onchocerciasis ___________________________________________________________________ 1875 O'Neill discovered microfilariae in skin biopsies in West Africans with a skin condition known as "craw-craw" 1893 Manson reported the personal communication to him by Leuckart of the discovery by a German doctor in Ghana of adult worms in nodules removed from the subcutaneous tissues 1916 Robles discovered Onchocerca infection in Guatemala 1917 Robles postulated on epidemiological grounds that Simulium flies may be the vector of Onchocerca in Guatemala. and suggested a relationship between this infection and eye disease 1920 Montpellier and Lacroix in Africa once more drew attention to the presence of microfilaria volvulus in the skin and related this infection to dermatitis 1925 Silva observed a microfilaria in the eye with an ophthalmoscope 1926 Blacklock in Africa described the development of microfilaria volvulus into infective larvae in S.1. although adult worms were not killed 1948 Mazzotti suggested that the precipitation of a rash by diethylcarbamazine could be used as a diagnostic method 1949 Garnham and McMahon eradicated flies from a limited focus in Kenya by applying DDT to streams 1982 Aziz and his colleagues indicated that ivermectin greatly reduced the density of skin microfilariae ___________________________________________________________________ . Transactions of the Royal Society of Tropical Medicine and Hygiene 57: 50-63.Onchocerciasis 691 McLEAN DS. but failed to transmit infection experimentally to monkeys 1928 Ochoterena demonstrated histologically the presence of microfilariae in the eye and optic nerve 1930 Torroella observed microfilariae in the cornea and anterior chamber with a slit lamp 1930 Hoffman showed that species of Simulium were the vectors in Central America 1931 Hisette emphasized the ocular manifestations of onchocerciasis in Africa 1947 Van Hoof and his colleagues showed that suramin killed adult worms but various workers found this drug to be very toxic 1948 Mazzotti and Hewitt reported that skin microfilarial density fell after treatment with diethylcarbamazine. damnosum. 1963 Table 25. Chapter 26 Dracunculus medinensis and GUINEA WOR M DISEASE SYNOPSIS Common names: Guinea worm, Medina worm, dragonneau, causing dracunculiasis, dracontiasis Major synonyms: Filaria medinensis, Fuellebornius medinensis, Gordius medinensis Distribution: West, North and East Africa, Middle East, Indian subcontinent Life cycle: First-stage larvae released from gravid female worms into water are ingested by small crustaceans (Cyclops) in the body cavity of which they moult twice to become infective forms. When humans ingest water containing infected Cyclops, the larvae escape from the crustacean and migrate through the duodenal wall into the retroperitoneal connective tissues. There they mature and mate. The female worms migrate through the connective tissues, usually to the lower limbs, and the female worm, about 1 metre long, appears in the base of an ulcer approximately one year after ingestion of the parasite Definitive hosts: humans (dogs, cats, monkeys, raccoons) Major clinical features: ulcer, secondary infection Diagnosis: macroscopic appearance, larvae in discharged fluid Treatment: metronidazole, niridazole, thiabendazole suppress inflammation and aid in mechanical extraction of the worm AWARENESS OF THE ADULT WORM Guinea worms have been known since antiquity in parts of Africa and th e Middle East. The parasite is probably mentioned in the Egyptian Papyrus Ebers (c.1550 B.C.) 99. Thus, Hoeppli49 believed that the following selectio n from this papyrus is possibly a description of the treatment of an infection with Guinea worm; "-----" represents the lesion and cannot be translated wit h certainty: If thou examinest a swelling of ----- in any limb of a man, then thou shalt apply a bandage to it. If thou findes that it goes and comes, piercing through the flesh which is under it, then thou shalt say concerning it; ----- has entered (?). Thou shalt perform an operation for it, the same being split with a....knife and seized with an ....instrument (forceps); that which is in its interior is seized with a forceps and then thou shalt remove it....That which is like the head is seized. 29 It is certainly true that dracunculiasis was endemic in Egypt at the time for the calcified remains of a Dracunculus have been identified in the mummy of a 693 694 A History of Human Helminthology teenage girl entombed around 1,000 BC 22. The theory was advanced in 1855 by Küchenmeister 59 that the "fiery serpents" which attacked the children of Israel in the desert during their exodu s from Egypt (c.1250 BC) were in reality Dracunculus medinensis , thus making the Mosaic passage in Numbers 21: 6 (th ought to be written in 8th century BC) one of the earliest recorded references to the worm: "Then the Lord sent fiery serpents among the people, and they bit the people, so that many people o f Israel died" (Revised Standard Version). Küchenmeister's postulate has been accepted with enthusiasm by some but rejected by others 5,6,124. The affliction was mentioned by Agatharchides of Cnidus (2nd quarter of the 2nd century BC), a geographer and teacher of one of the sons of Alexander Ptolemy VII. The original manuscript has now been lost but Plutarch (c.46-120 AD) refers to him in the eight book of his Symposiacon (Table talk) where he makes him narrate: The people who live near the Red Sea are tormented by an extraordinary and hitherto unheard of disease. Small worms issue from their bodies in the form of serpents which gnaw their arms and legs; when these creatures are touched they withdraw themselves and insinuating themselves between the muscles give rise to horrible sufferings.1 The condition was also known, either by experience of as a result of hearsay, to a number of other Greek and Roman writers including Pliny (23-79 AD) , Soranus of Ephesus (c.100), Julius Pollux (c.185), Galen (129-c.200), Aetius of Amida (c.550) and Paulus Aegineta of Alexandria (c.840). It was described by a number of Persian-Arab physicians including Rhazes (died 928) an d Avicenna (980-1037). Among the first Europeans from non-endemic areas to come in contact with the worm were Amatus Lusitanius, van Linschoten , Alexei de Abreu, Edward Wotton, Thomas de Veiga, Joh. Gorraeus, Mercurialis and Ingrassia, all in the sixteenth century. Considerable uncertainty surrounded the nature of the affliction. Som e authors including Aetius, Paulus Aegineta, Rhazes, Amatus Lusitanius, Alexei de Abreu, Wotton and de Veiga apparently regarded it as a worm. Others , however, thought it was a corrupt nervous substance (Soranus, Pollux, Galen, Paré), a tumour or abscess (Gorraeus, Aldrovandi, Montranus), an elongated vein (Guy de Chauliac), black bile (Tagentiu s), fibrous concretions (Richerand) or atrophied cellular tissue (Larrey). It is also not always clear precisely what some of the early writers thought was the nature of the worm. The Persian-Arabic physician, Avicenna (= Abu Ali al Husain ibn Abdallah ibn Sina) is a case point. According to Hoeppli 49, Avicenna denied its animal n ature, believing it to be a vein. Amatus Lusitanius (1511-1568) was also of this view, f or he wrote in Latin (translated by Singer): A certain Ethiopian slave....was seized with pain in the leg. An ulcer developed, in which vein-like structures became prominent....The Arabian physicians especially Avicenna....describe it as the Medina vein.9 On the other hand, Singer provides the following English translation of a Latin Dracunculiasis rendition by Velschius of Avicenna's text: 695 In the meanwhile a vermicular movement can be distinguished beneath the skin as though some live thing were there, and indeed as we shall see, a worm is present, for so at least some regard the thing that has arisen. 8 From the overall sense, it seems pretty certain that Avicenna was indee d referring to a worm, but the difficulty apparently lies in the accurate translation of the original Arabic (Ark, Aerk, Irk or Erk Almedini) which the Greek and Latin translators of the Middle Ages, having no opportunity of seeing th e creature, rendered as "Vena seu Nervus medinensis" (vein or nerve fro m Medina). Thus, Andry (1700) wrote: "Avicenna calls this Worm by the name of Vena by reason that it resembles a small vein" 3. According to Hoeppli again, the work Ark simply means something long, thin or filariform 49. Küchenmeister, however, quoted one autho rity in support of the suggestion that perhaps it meant "to corrode" or " to gnaw away", thus indicating that it referred to a worm which gnawed away at the flesh 59. Because of this uncertaintly , different translators have therefore used different words in their translations , depending upon their personal preferences. Examples of these various opposing views are provided by Paré and by de Veiga: "This little dragon is not a worm, nor indeed any living Thing, but only a Swelling and an Imposthum e occasioned by too hot Blood" 101 compared with "Whoever entertains such Doubts has taken a narrow view of 'em. 'Tis certain this worm moves" 132. Such confusion lasted for many cent uries for as late as 1824 superintending Surgeon Milne of Bombay, India wrote: The substance in question cannot be a worm because its situation, functions and properties are those of a lymphatic vessel and hence the idea of its being an animal is an absurdity.85 Nevertheless, the opinion that the pathology in question was due to a worm gradually gained ground. Amatus Lusitanius (1551-1568) left no doubt as to his own views when he wrote: Authors are in doubt whether this is a nerve, a vein or a worm. But I have seen the condition with my own eyes, and can bear witness that a thin, white worm in many coils was drawn forth.2 In 1674, Georg Hieronymous Velschius (Welsch) wrote a large monograph of 456 pages on the single subject of dracunculiasis. He saw drancunculi everywhere including on ancient Roman emblems, in the signs of the zodiac, among marine nemertines and polychaetes, in Arabic lettering, in many Gree k sculptures and in the emblem of the medical profession (serpents coilin g around the staff of Aesculapius which he interpreted as a Guinea worm jus t extracted by entwining it around a piece of wood) but asserted that dracunculi were definitely alive and verminous 133. Amongst those who accepted the verminous nature of disease, there wa s considerable confusion concerning the morphology of the creature. Thus , Nicholas Andry wrote in 1741: Two things have to be pointed out concerning this worm: 1. It has two heads: not 696 A History of Human Helminthology one at the side of the other, but one situated at one end, the other one at the other end, as in some caterpillars. 2. Always one of the two heads appears dead, whereas the other one appears alive.3 Linnaeus recognized it as a worm and in 1758 in his Systema Naturae, classified the parasite in his Class Vermes, Order Intestina, naming it Gordius medinensis 71. The specific name, as already inferred, was derived from it s prevalence around the Arabian city, Medina, as was recorded by Avicenna : "The disease is commonest at Medina, whence it takes its name" 8. In the revision by Gmelin of Systema Naturae (thirteenth edition) published in 1788, the worm was transferred from the free-living species of Gordius to the genus Filaria of Müller (see chapter 23) and it became known as Filaria medinensis for some years 43. Any lingering doubts as to the animal nature, specifically the helminthi c nature, of the parasite should have been dispelled by the discovery in the early nineteenth century of the embryos (lar vae) released by the parent worm (as will be described later). The first detailed description of the worm's anatomy was published in 1868 by the Englishman, Henry Bastian, and put paid to an y lingering reservations that D. medinensis was in fact a worm. He examined six specimens which had been taken from the lower extremities of a Britis h surgeon in Bombay by a native of that Indian city. The parasites varied i n length from 18 inches to three feet and macroscopically were: of a milk-water colour....mostly quite smooth,....cylindrical, more or less flattened laterally and tapering gradually towards both extremities. About 1/20 of an inch from the posterior extremity the body becomes more abruptly narrowed, and terminates usually in a sharply curved tail or point....No vulva discoverable; and aperture doubtful....The integuments are so elastic, that the worm may be stretched to nearly twice its natural length.10 Bastian then described the appearance under the low power microscope of the small head, the lamellar nature of the chitinous integument, four powerfu l longitudinal muscles, two delicate ganglionated chords extending the whol e length of the worm, four longitudinal "circulatory vessels" and the gut. All the worms were female and viviparous. He found th at the reproductive organs were huge: The genital apparatus consists of a large, highly organized sac or uterus, distended with young Filariae and a little fine granular matter. It occupied the whole of the peritoneal cavity....except from one to two and a half inches from the anterior extremity and about a quarter of an inch or less from the tail. Both anteriorly and posteriorly, this sac terminated abruptly in a small tube twisted several times around the intestine, or forming a knotted glandular-looking mass. 10 In 1879, Fedchenko improved upon the description of the anatomy of the worm. He found a basal granular layer in the hypodermis which formed th e outer layers of the integument, discovered some transverse muscle fibres , discussed the morphology of the head, excretory system and gut, layin g particular attention upon the oesophagus and surmising that the worm ingested food, and concluded that the uterine appendages were ovaries 36. Dracunculiasis 697 Bastian was intrigued by the failure to find any male worms and speculated that either the males never attained any great size and therefore failed to attract attention whereas the enormous development of the genitalia of the female s made them so large that they became palpable in superficial situations, o r possibly, that the male worms, in contrast to the females, never entered th e body. The former hypothesis was proven correct when RH Charles at las t discovered the male worm. During an autopsy in Lahore, India in 1892, h e found two nematode worms in the subperitoneal tissues which he regarded as immature D. medinensis. He went on to say On examining two....I was struck by seeing something growing from the side of each of them. This 'something' I found to be a roundworm with the characters of that to which it was attached. On drawing upon it with forceps I found, to my astonishment, that it was possible to pull it out of the body of the larger worm from a small opening near its middle....I did not completely pull it out and only withdrew it about 1 cm.18 Charles was of the opinion that the "something" was a male Dracunculus but failed to provide convincing evidence to support his case. A contemporar y commenator wrote in the British Medical Journal : Before subscribing to Dr. Charles's views, we should like to see a more detailed account of the structure of this "something"....Dr. Charles gives no account of the head, tail, testicle, alimentary canal, spicules, papillae, or any of those features characteristic of male nematodes. Until these are fully supplied we suspect that helminthologists will be inclined to regard Dr. Charles's supposed male filaria medinensis as being probably a hernia or the uterus or alimentary canal of the female....It is quite possible however, that Dr. Charles in right of his views; but in bringing them forward the least he could have done, in justice to himself and in the cause of science, was to use every means in his power to justify the position he assumes and to make it unassailable. It is not too late yet if he has the interesting specimens he so meagrely describes in his possession. 7 Subsequently, Leiper (1906) found two male worms about 22 cm long in an infected monkey 61. Surprisingly, he never provided a detailed description of their morphology yet he did not encounter the censure that Charles ha d received. The first substantial account of the morphology of the mal e Dracunculus was provided in 1937 by Moorthy 86. In his discussion of the anatomy of the Guinea worm in 1863, Bastia n remarked that he doubted the propriety of considering the worm as a species of the genus Filaria. Of the many names which had been used to designate the worm previously such as "de vena medinensis" 133, "de dracunculo Persarum" 57 and "de verme medinensis" 46, two of these "dracunculus" (derived from th e Latin word "draco" meaning "snake", "serpent" or "dragon") and "medinensis" were adopted into binary nomenclature (i.e. Dracunculus medinensis ) by Cobbold in his text book of the following year 20. In 1915 by Opinion 66, th e International Commission on Zoological Nomenclature approved this name , Dracunculus medinensis being the type of species of the genus Dracunculus 53. The first person to use the name "Dracunculus" after 1758 (the starting point for binary nomenclature following the appearance of the tenth edition o f 698 A History of Human Helminthology Linnaeus's Systema Naturae) had been Reichard in 1759 115, and it was this name which was given official sanction. This was later disputed by Leiper , however, on the ground that Reichard only used it in a vernacular sense in his thesis. Leiper applied the same criticism to the use by Gallandat in his thesis in 177342 of the term "medinensis" to modify "dracunculus". Despite Leiper' s objections and his attempt to change the name to Füllebornius medinensis 65, the official name Dracunculus medinensis (Linnaeus 1758) Gallandat 177 3 still stands. With respect to its common name of Guinea worm, Sir James Tennent , Colonial Secretary of the British Government in Ceylon (Sri Lanka) wrote: these pests in all probability received their popular name of Guinea worm from the narrative of Bruno or Braun, a citizen or surgeon of Basle, who about the year 1611, made several voyages to that part of the African Coast, and on his return, published amongst other things, an account of local diseases. 127 EARLY THEORIES ON THE MODE OF TRANSMISSION The belief that Guinea worm was acquired from water was embedded deeply in the folk-lore of the inhabitants of many endemic areas. This was accepte d and reported by a number of European adventurers who began visiting suc h regions in the sixteenth century. The Dutch navigator, Jan van Linschoten , journeyed to the East Indies and on his return to Holland wrote a number o f books which became very popular and were translated into many Europea n languages. In 1584, he had visited Hormuz (Ormus, Ormusz) in the Gulf o f Oman (Persian Gulf) and wrote: "There is in Ormus a sickness or commo n plague of wormes, which growe in their legges, it is thought that they proceede of the water they drink"73. Van Linschoten also noted that the place was so hot that the inhabitants slept at night immersed except for their heads in troughs of water and "Thus it comes about that they are infected by worms, which grow in their legs, and are two or three feet long" 73. Thus, not only did Linschote n recognize an association with water, but he appears to have canvassed the two ideas which were to become a recurring theme over the next three centurie s concerning the acquisition of infection - ingestion of worms and penetration of worms through the skin. About the middle of the seventeenth century, Monseigneur de la Mott e Lambert, Bishop of Beirut, undertook a pastoral tour of the Middle East and a record of his experience was published. He found that in the town of Lau i n Persia (Iran): the water....is very bad and the cause of severe and mortal diseases. To this bad water supply throughout the country between Lau and Gomeron may be attributed worms of a prodigious length which engender in their thighs and legs 12 In the latter part of the same centu ry, a British traveller to the East Indies stated in the Philosophical Transactions , concerning the Guinea worm with whic h he had been afflicted: "These worms are bread by the water, between Gomroom Dracunculiasis 699 and Schiraz, especially that about Laur" 74. The resemblance of Guinea worms to the free-living Gordius aquaticus or "hairworm" inhabiting ponds and rivers led some 18th century writers such as Meyer to suppose that the entozoon was really the latter worm which ha d penetrated the cellular tissues 84. Similarly, Linnaeus thought that the Guine a worm normally lived outside the human body, but when pathogenic, introduced itself through the skin of the legs 72. The Englishman James Lind (w ho introduced citrus fruits as a prophylactic against scurvy at sea) showed much more insi ght into the mode of transmission, however, when in 1768 he wrote: and thus supposing the guinea worm to be generated from animalcula or their ova contained in the waters of the country, their production in the human body may probably afterwards be prevented by drinking those waters only that have been rendered perfectly sweet by undergoing a previous putrefaction. 68 Lind achieved this purification by first sealing containers of pond water from the endemic areas in West Africa until microscopical examination indicate d that all the animals were dead, and then foll owing this with sieving of the water. At around the same period, the Frenchman, Gallandat, also favoured th e theory that infection was acquired by ingestion of water because his observ ations led him to believe that those who drank no water in Guinea escape d infection41. Likewise, the Briton, Colin Chisolm (1795) in Grenada noted with respect to Guinea worms that "the cause of this singular disease....seems to be confined to the water of some wells" 19. Chisolm found strange animalcules in such water and showed that the disease could be prevented by the filling in of the wells. Similarly, Ferg in Surinam rep orted that an outbreak of Guinea worm infection had occurred on a plantation in Surinam in 1801 and noted that both the field-hands and the household slaves, who had nothing in common except the water supply, became infected 37. On the other hand, there were several anecdote s which seemed to go against the theory that infection was acquired from ingestion of contaminated water . Küchenmeister59 quotes two such instances. While in Curaçao (Netherland s Antilles), Jacquin, who drank much water remained free from infection , whereas his companion who consumed only spirituous liquors was affected . Similarly, a Dutch general in Angola a te and drank nothing but food and beverages brought with him from Europe yet acquired the worm. Similarly, several observations by British medical offic ers in India also seemed to militate against the water ingestion theory. In 1806, Bruce claimed that watercarriers in India who carried leather bags on their backs suffered from dracunculiasis chiefly in those same parts 14. This claim was supported by Scott but rejected by a number of other observers including Smyttan, Morehead and Ewert. In 1816, Heat h reported that in an outbreak of dracunc uliasis amongst the crew of a ship which had lain for a long time in the port of Bombay, only the crew became infected whereas the officers remaine d free of the infection; both groups drank from the same water supply, but only the officers wore shoes while on shore 47. 700 A History of Human Helminthology Consequently, these events were interpreted as indicating that infection wa s acquired from water through the skin. All this remained mere speculation, however, and no significant advances could be made until the offspring of the Guinea worm were identified. Th e embryos of D. medinensis, and the fact that female worms were viviparous , were discovered and first reported in 1819 by Rudolphi in his major work , Entoozorum Synopsis, wherein he wrote: "Filariae nostrae prole quasi farctae sunt, quod si harum longitudinem illius vero minutiem spectas, foetuum multa millium milklia singulis tribuit" 121 which may be translated roughly as saying that if the longitudinal organs of the worm are in fact observed closely, many thousands of individual embryos may be discerned. This remark lay buried among so much other data, however, that littl e notice appears to have taken of the observation and the phenomenon had to be rediscovered several times before the fact became known widely. The firs t person to do this was Jacobson in Copenhagen who examined a Guinea worm removed from a 13-14 year old b oy who had been born on the coast of Guinea; he recounted his findings in a letter send to M. Blainville in Paris in 1834 55. In the following year, Duncan in Calcutta, India also found on microscopica l examination of Guinea worms that the uteru s was packed full of embryos 27. The presence of embryos was soon verified in that country by Forbes 38 and by McLelland75. The existence of embryos was then reaffirmed in Europe by the Parisian surgeon Maisonneuve in 1844. In 1840, Maisonneuve had examined a 28 year old patient who had spent two and a half years soldiering in Senegal and had contracted dracunculiasis. During extraction of the worm, a few drops of white fluid, like whey, escaped and microscopical examination disclose d myriads of small cylindrical, amazingly active worms with pointed tails 80. Furthermore, continued observation revealed that they remained alive for one to two days. Maisonneuve commented that when the time for reproducin g arrived, the worm makes an ef fort to perforate the skin in order to discharge its young into the external environment. As already mentioned, the question which followed naturally from all o f these observations concerned the manner in which infection was transmitted to another host. Once Duncan had found embryos in the Dracunculus uterus, he was stimulated to search the envi ronment. He reported that "the soils and pools abound in the rains with a worm smaller and more slender, but otherwis e exceedingly like (Guinea worm)" 27. Likewise, Forbes in Darwar, India als o looked in water for worms and may well have found larvae liberated by female worms for he wrote: I examined several of the tanks in the neighbourhood and found the mud on their banks and in their half dry beds abundantly supplied with animalcules, some of them resembling very much those produced by the guinea worm when infecting the human limb....Two kind of these animalcules may be detected in the soft mud: one kind seven to eight times the size of the guinea worm animalcules, the other exactly resembling it.38 In the same vein, Brett (1840) claimed to have found Dracunculus in the Dracunculiasis 701 flood-plains on the banks of the river near Dhun in India 13. It seemed likely, therefore, that the released embryos were carried through the medium of water, in which case t wo modes of entry seemed possible; either the worms could be ingested in contaminated water or the larvae coul d penetrate the skin when humans waded in infected water. The first person t o investigate these possibilities experimentally appears to have been Forbes in India in 1838. He obtained fr esh larvae from the leg of a sepoy (Indian soldier) then gave them to two pups. On examination of the dogs, one 4 hours and the other 24 hours later, he foun d the worms dead in the mucus of the stomach and duodenum38. This seemed to oppose the ingestion theory and gave credence to the idea that infection was acquired by worms penetrating the skin. In 1855, Carter in Bombay, India published some epidemiological observations which he also interpreted as supporting this latter concept. Over th e period of a year, 21 out of 50 boys in the School of Industry in Bombay ha d been infected with Guinea worm, although none who had been admitted to the school within the last year had b een so afflicted. The boys lived in an enclosure bounded on three sides by the sea and on the fourth side by a cliff. Within the enclosure were two wells, one three feet and the other six feet in depth; th e former was used for providing drinking water and the latter for bathing. I n addition to the boys, the wife of the sergeant who superintended the school was also infected; she bathed in the well but obtained her drinking water fro m elsewhere. Carter examined these tanks and found minute worms closel y resembling the young of guinea worms. In ano ther school, where dracunculiasis was absent, he could not find these "tankworms" and concluded that infection was acquired by bathing in, not by th e drinking of, water which contained these "tankworms" 17. The idea of skin penetration gained ground, and despite the fact that nothing had been proven, an anonymous writer in The Lancet of 1867 asserted dogmatically: The most contradictory opinions have been expressed by correspondents in the daily journals on the subject of guinea-worm disease. The real facts of the case are simply these. In certain tropical parts, minute worms abound in stagnant pools and swampy ground. These have the power of penetrating the skin, in virtue of their "boring" properties, and subsequently grow to a large size, causing, after a few months, local irritation and the formation of a quasi-abscess, which is a provision of nature to aid expulsion of the worm. The lower limb is the part most usually attacked, and the worm makes its way thither via the feet of natives, and simply because they are commonly unprotected and in contact with the bare ground. But Europeans would be equally liable to guinea-worm disease did they go about with bare feet. 4 Several years later, however, all this was to change with the epocha l discovery of Fedchenko. 702 A History of Human Helminthology ELUCIDATION OF THE MODE OF TRANSMISSION: DISCOVERY OF THE CRUSTACEAN INTERMEDIATE HOST In the three years between 1868 and 1871, The Russian naturalist, Alekse j Fedchenko, and his wife lived in Turkestan , Samarkand and Tashkent in central Asia. It was during this period that he made his original observations on D. medinensis. Fedchenko made arrangements in 1869 with one of the loca l doctors to provide him with Guinea worms extracted recently from infecte d persons. His first attempt to study the fate of the embryos failed when he killed them by adding fresh well water which was rather cold and was rich in lim e salts. He then told how: an incident helped me in my research....On the 5th of July, in the small bottle in which (the doctor) had brought a guinea worm, I noticed a pair of small water crayfish - the Cyclops. Placing them under the microscope, I saw in each one several familiar looking embryos of the guinea worm.36 In order to convince himself that the embryos of the Guinea worm reall y entered the Cyclops, he performed an experiment. He punctured a Dracunculus and placed the embryos in a watch glass. He then added water and Cyclops which he had assured himself were free of any larvae. Although he did no t succeed in determining whether the embryos were ingested or whether the y penetrated the cuticle of the Cyclops, he discovered that "after several hours a significant number of embryos appeared in most of them, especially in males and particularly in young specimens" 36. Fedchenko found that there wer e usually five or six larvae lodged in the body cavity of each minute crustacean. He watched the evolution in the appearance of the worms over the succeeding weeks. During the first few days, the gut became more developed, then afte r two weeks the larva moulted and lost it s tail. By three weeks, the differentiation of the internal organs had become more pronounced with the rudiments of the reproductive organs appearing. Finally, Fedchenko provided an illustration of a larva after a sojourn of one month in the crustacean. He presented his findings to a meeting of the Imperial Society of Friends of Natural Sciences , Anthropology and Ethnography in Moscow on 21 January 1870, his pape r being published later that year in the Proceedings of the Society 36 Fedchenko wrote that at the beginning of his studies he had placed Dracunculus larvae in a small aquarium containing different water animals in th e hope that Guinea worm, like so many other parasites, would live first in some such animal then pass on to man. He made no mention in his paper, however, that he had been advised by others to follow any particular line of enquiry . Indeed, by recounting the incident of 5 July, he implies that his initia l observation with Cyclops was serendipitous. This does not seem to be a n accurate portrayal of the preceding events, however, for Leuckart 67 remarked that he had met Fedchenko in 1868 and had advised him to look for th e development of D. medinensis in Cyclops because of the similarity between its Dracunculiasis 703 embryo and that of Cucullanus elegans, a parasite of perch, the life cycle o f which Leuckart had already work out and publis hed in 1865. Cobbold, who had met Fedchenko when the latter visited London in 1873 later wrote: It is only fair to add that the Russian traveller was led up to his discovery by the previous investigations of Leuckart concerning the young of Cucullanus. The Leipsig helminthologist had, indeed, specially instructed Fedschenko as to the probable source of Dracunculus. It is often thus that science makes its clear advances, since a master-mind is needed to set others on the right track. 21 A more important, but undoubtedly erroneous, criticism of Fedchenko' s contribution was expressed by Manson-Bahr in his textbook in 1966 when he wrote: Fedchenko (1869) is credited with the discovery of the transmission of the guinea worm, but probably Manson was the original observer (1895). Leiper believes that the stages figured by the former are those of Cucullanus (a parasite of fish), not of D. medinensis.83 In fact, Leiper had been much more circumspect than this. He had merel y observed that Fedchenko's paper, published in Russian in 1870, was ver y inaccessible and that two of the illustrations of purported Dracunculus given in Leuckart's textbook 67 were undoubtedly based upon a specimen of a Cucullanus larva66. Manson-Bahr's statement brought forth a response fro m Hughes in defence of Fedchenko. He arranged for Fedchenko's paper to b e translated and summarized it by saying that w hatever the defects in Fedchenko's drawings, his written account was convincing enough 52. Final confirmation of the validity of Fedchenko's discovery was provided shortly thereafter whe n Muller published a reproduc tion of Fedchenko's original drawings and showed that it undoubtedly represented a D. medinensis third stage larva 92. Although Fedchenko discovered that D. medinensis larvae grew and moulted in the crustacean, Cyclops, he was unable to complete the cycle o f transmission. He posed a rhetorical question, then went on to postulate, with accurate foresight, the subsequent course of events: What then happens to the embryos at a later stage? It seems to me that, taking into consideration the known facts concerning the development of other roundworms, one can state the following: Cyclops, with the embryo, enter the stomach of man through drinking water; here, under new conditions, further development occurs pertaining primarily to the genitals. The differentiation of males and females occurs, and copulation takes place. Thereafter, the males die; however, the females, to develop their offspring, take off by unknown means, toward the skin where they place themselves subcutaneously.36 In support of this hypothesis, Fedechenko drew attention to a multiplicity of diverse observations: all specimens studied so far were female; Pruner i n Egypt had discovered a worm in the liver; the head of the worm pointe d towards the skin; the fact that in Asia the infection occurred only where th e inhabitants were forced to drink stagnant water and that these people, i n contrast to the Hindus of India, did not go barefoot and rarely bathed but, i n accordance with Muslim custom, washed their face and hands five times each 704 A History of Human Helminthology day with their hands. He concluded by saying that: Now, experimentation is needed - similar to the feeding experiments conducted in studying tapeworm or other parasitic worms - to prove whether the Cyclops, with the embryo of Filaria, swallowed by a human being, is the cause of guinea-worm disease.36 According to Cobbold 21, Fedchenko himself did later undertake some desultory experiments in this regard but without success. He fed infected crustaceans to dogs and cats, but failed to rear dracunculi in these animals. This did not put Cobbold off for he remarked: Clearly, these carnivora were unsuitable hosts. Could Fedchenko have experimented on man the results would probably have been very different. Arguing from what happens in the case of Cucullanus amongst fishes, and Trichina in man, there can be little doubt that all further and final changes undergone by the larvae are accomplished within the human host.21 Rather surprisingly, more than 20 years were to pass before anyon e repeated Fedchenko's important experiments. In 1894, Patrick Manson had a patient with Guinea worm infection in the Seaman's Hospital in London. H e collected a supply of embryos from this patient and mixed them with a number of Cyclops procured from neighbouring ponds. Twelve hours or so later, h e found that nearly every one of the copepods had 10-20 larvae coiled an d wriggling within the body cavity. He believed that infection had taken place by penetration of the joints in the integument. Over the ensuing weeks he watched the slow metamorphosis of the worms. He repeated the experiment in th e following year and found that, in contrast to Fedchenko's belief, the enclosed larvae moulted not once but twice 81. In 1905, Leiper studied dracunculiasis on the Gold Coast (Ghana) of West Africa and performed a new series of experiments in which Cyclops was infected. He thought it probable that the crustaceans were infected via their oral cavity; this view was later to be proven correct by Turkhud 129 and by Roubaud119. Furthermore, Leiper found that once metamorphosis was complete, the larvae lay quiescently within the crustacean for several weeks. Whe n hydrochloric acid was added to simulate t he acidity of gastric juice, the Cyclops were killed but the Dracunculus larvae regained their former activity an d escaped from the disintegrating intermediate hosts. He interpreted thes e observations as indicating that once the worms were set free in the stomach of the human host, they were able to proceed with further development within the human body 60. The species of Cyclops which Fedchenko in the USSR and Leiper in West Africa used are uncertain. That used by Manson in England was probabl y C. quadricornis. Other species, including C. leuckarti 119, C. hyalinus 87 , C. nigerianus 96 and C. vernalis 125 as well as other carnivorous species of Cyclops were later shown to be infected. While still in West Africa, Leiper turned his attention to attempting t o complete the life cycle of the parasite. In 1898, Plehn in the German Camer- Dracunculiasis 705 oons (Cameroon) had claimed to have found a female worm, indistinguishable from the Medina worm, in a monkey eight months after feeding it banana s containing first-stage larvae 102. In the light of hindsight, however, it must b e concluded that the relationship between these two events cannot be causal. In order to prove whether or not an intermediate host was necessary, Leipe r induced a monkey to swallow thousands of newly-liberated embryos, but n o sign of infection could be found at a utopsy six months later. He must have been convinced absolutely that a vector was required for he applied living embryos to the dorsum of his own hand; no erythema or itching occurred and no patent infection developed subsequently 62. He then fed a monkey on bananas wit h Cyclops that had been infected with D. medinensis for five weeks. Six months later, he and Dr. Daniels made a careful post-mortem examination and found five worms which possessed all the characteristics of D. medinensis. Three were immature females about 30 cm long, and the other two were small male worms 22 mm in length 61,62. He concluded that: these results point strongly to the truth of the theory that infection of man takes place from the drinking of water containing infected cyclops....The finding of both male and female forms in the connective tissues relieves us of the more improbable alternatives previously open to us....The view that larvae at once make their way through the gut wall and become sexually differentiated later in the tissues of their host, brings the after-development of the parasite much more into line with that of other filariae62 In discussing the great frequency of infection in the lower limbs of humans , Leiper noted that in his experimental monkey, the female worms had made their way into the limbs, being found in the forearm, axilla and popliteal space. He remarked that "geotropism" seemed to him to provide the most likel y explanation for the distribution of the parasite. Several years later, Turkhud in the Bombay Bacteriological Laboratory in India attempted to repeat this experiment. Numbers of monkeys were infected orally with living first-stage larvae or with infected Cyclops, while others were given embryos by subcutaneous injection. Post-mortem examinations wer e made up to one and a half years later, but no dracunculi were ever found 130,131. Consequently, five "volunteers" ingested five infected Cyclops containing a total of 6-8 D. medinensis larvae on 5 April 1913. On 18 March 1914 (38 4 days later), one of the volunteers, a laboratory assistant who had remained well during the interval, developed a small blister on his right foot together wit h fever, vomiting and diarrhoea. On the 30th of that month, the blister was found to contain D. medinensis embryos. None of the other four subjects developed patent infections131. Turkhud may well have completed the life cycl e experimentally, but this report must be viewed with some circumspection as the area was endemic for dracunculiasis and the infection could have been acquired naturally. Several other unsuccessful attempts were made to repeat Leiper's exper iment with monkeys 32,119 until Brug in the Dutch East Indies in 1930 recovered 706 A History of Human Helminthology a full-grown female worm from the calf of a gibbon 15. Four years later, Issajev in the Soviet Union reported that in a series of experiments between 1927 and 1932, he had infected 42 dogs orally and obtained female worms from 27 o f them54. In 1936, Moorthy and Sweet confirmed this result by indicating tha t they had produced patent infections in a number of dogs. Furthermore, the y recovered a large number of male and female worms 88,90. It was this latter experiment which finally provided a definitive description of the male worm, thus completing all the major links in the life-history of D. medinensis. It remained to define the route of migration of worms within the body of the definitive host. Onabamiro (1956) could find no trace of worms in dogs until 43 days of infection, when he found them par ticularly in the axillae and inguinal regions, thus suggesting that they may have migrated there via the lymphati c system97. Muller then investigated the early route of infection in dogs, cats and monkeys; he found larvae in the duodenal wall 13 hours after infection, in the abdominal mesentery for up to twelve days, then in the thoracic and abdominal muscles at two weeks. He thought it likely that a moult took place and th e worms migrated to the axillary and inguinal subcutaneous tissues. The mal e worms died between three and five months after infection and became encysted while the female worms began moving down the extremities between the eighth and tenth months 93,94 DETERMINATION OF THE INCUBATION PERIOD The time required for development of worms in these experimental infections was consistent with the period thought to be necessary for the development of patent infections in humans. It had long been known that a number of months were required for clinical expression of the infection. Kuchenmeister (1855 ) remarked that the infection was asymptomatic for a long time 59 and Moquin-Tandon (1861) wrote that the incubation period varied between two months and a year or more 91. In 1880 G Mackay, a retired Deputy Surgeon General of the Indian Army, recorded that a regiment of native infantry arrived at Madras in February 1860 when dracunculiasis was rampant. In Februar y 1861, the first cases of Guinea worm infection amongst the troops wer e admitted to the regimental hospital; during the following four months, 13 5 cases, being 25% of the strength of the regiment, occurred. Mackay wrote: Having had many opportunities of observing the origin and progress of this most troublesome and often formidable parasite, I believe that a period of from eight to twelve months is necessary for the full development of the worm in the human system79 Cases which occurred in expatriates aft er leaving endemic areas provided more certain evidence of the minimum time required. In 1879, Fox reported th e instance of a young Englishwoman in whom a Gu inea worm had appeared eight months after leaving India 40. In 1909, Manson recorded the occurrence o f Dracunculiasis 707 infections in two Englishmen who had been exposed in the Sudan twelve plus or minus several months previously 82. In the following year, Powell reported an event in which 16 Indians were exposed during a three day period from 20-22 April 1902. The first worm appeared in the first patient on 3 April 1903 (h e discharged eight more over the next three months). Six more of the party were similarly afflicted between 1 May and 20 May 1903, giving incubation periods ranging between 345 and 437 days104. A somewhat shorter pre-patent period was reported by Wurtz and Sorel. In March 1911, they paid a visit of thre e hours to a village in the Ivory Coast where they noticed many cases of drac unculiasis; 260 days later, two of their se rvants were found to be infected 134. All these observations left little doubt that a period of approximately one year was required between acquisition of infection and the presentation of the adul t female worm. RECOGNITION OF THE CLINICAL FEATURES The clinical manifestations of dracunculiasis have been apparent for all to see since time immemorial. At the beginning of the second millenium AD , Avicenna succinctly described the condition: The signs of this condition are as follows. A pustule first appears and swells up, but afterwards contracts down again to a mere bleb. Soon, however, the bleb perforates and dark red matter is continuously exuded. In the meanwhile a vermicular movement can be distinguished beneath the skin. For the most part it is the legs that are involved, but I have seen cases in which the hands and even the sides are affected.... Should the worm be ruptured, much pain and trouble ensue, and even if rupture does not take place, the condition is tiresome enough. 8 In the late seventeenth century, Lister, an English traveller recounted vividly his own experiences. He related that he had known some sufferers who had been bed-bound for up to ten months, and that there were some who had lost their legs, or even their lives. He recognized that the severity of the disease wa s increased enormously if the worms were broken during their extraction: A few days after my arrival....the fruit of my journey showed themselves; for a little below the instep of my left foot, a worm put out his head....When mine first came out, for about 40 to 50 days, it came out every day little by little, without putting me to too much pain, but that I could go up and down till it was come out about a yard and a quarter; but afterwards, one day stirring too much, I hurt the worm and enraged him, so that he broke off of himself, and going in, caused my foot and leg (up to the calf) to swell till the skin was ready to burst, which kept me sleepless and cast me into a fever. I had a chirurgeon and kept my bed for about 20 days in which time I had several fits of the said fever.74 One thing above all struck most observers, and that was the remarkabl e frequency with which the worms presented in the feet. In 1805, McGregor in India reported that in 87% of h is series of 181 patients the worms were located in such a situation78, and this observation has more or less held true in al l 708 A History of Human Helminthology subsequent reports. For example, Forbes reported his experiences as a medical member of the Anglo-French Boundary Commissi on in the Gold Coast (Ghana) and French West Africa (Ivory Coast) colonies in 1902-1903. Forty percent of the 400 native carriers were afflicted wi th Guinea worm, the sites of emergence being the lower limb in 77% (feet in 22%), upp er limb in 9%, scrotum in 4.5%, abdominal wall in 4%, back or buttocks in 3.5%, face in 1% and penis in 1%. Nearly half of his patients had multiple infect ions, most of them having between two and ten worms39. Occasionally, massive numbers of worms are present ; Trewn reported the instance of a person who ha d 55 worms at one time 128. This, however, was not the general experience; more typical was the finding b y Fairley and Liston that the average number of worms per person in their series of 140 patients was 1.9 33 and the observation of Rao that 2,086 of 3,12 9 patients had only one worm 112. It has long been realized that most persons were quite unaware of th e presence of the worm during the prepatent period. In one large recent series, only one third of patients were a ware that anything was amiss before the blister appeared, and most of these patients only discerned a palpable worm several days earlier113. As the time for presentation of the worm approached, there was not infrequently urticaria, vomiting, fever, abdominal pain and sometime s dyspnoea, possibly produced by a toxin released by the worm 31,33. One somewhat racist commentator wrote in 1914: the patients being for the most part, in Africa at least, people of limited intelligence this testimony is unreliable. My opinion is that premonitory symptoms are not the rule; nevertheless they have been not infrequently described and are probably more common in Europeans.76 More objective investigators, however, have found that such symptom s occurred in 30-90% of their patients 16,26,33. In simple cases of Guinea worm infection, it was apparent that worm s extruded gradually over a period of four to six weeks, then the ulcer heale d leaving a scar. It was also realized from the earliest times 8 that if the worm ruptured, then severe inflammation was likely to follow. Secondary bacteria l infection often supervened; in a series of 218 cases, septic complications were present in nearly half of the patients 33. Sometimes, the worms failed to surface and became encysted and calcifie d in the tissues where they remained for many years23,114,118. Occasionally, the dracunculi were observed to enter a joint , especially the knee, where they sometimes liberated larvae into the synovia l fluid and precipitated a severe arthritis. Susceptibility to infection and resistance to reinfection is a vexed topic . Trewn, who had the experience of removing 526 guinea worms during th e space of three years, noted that some people never became infected eve n though they used the same water sources as did others who got yearly infections, thus implying that the former were immune, whether for constitutional or immunological reasons, whereas the latter had acquired no resistance t o infection128. This was confirmed by Rao who surveyed some 11,000 villagers 000 villagers in th e South Indian Deccan where infection rates ranged between 11 and 53%. Similarly. reinfections. by aspiration of fluid from the blister then examining it for the presence of larvae 131. and 10% of them had had ten or more attacks over the years112.. In a few seconds a droplet of whitish fluid will be seen to well up in the little hole. as was done by Turkhud in his experimental infections of a human. Diagnosis in the stage before rupture of the blister and presentation of the head of the worm may be made. Amatus Lusitanius wrote in the . THE SEARCH FOR EFFECTIVE TREATMENT The time-honoured method of treating dracunculiasis has been by winding the worm around a stick and pulling it out slowly. eosinophilia is characteristic o f dracunculiasis. and then suddenly rupture.Dracunculiasis 709 in India and found almost 30% infected.. then Roussel achieved a similar effect by the injection of lipiodol 120. Hudellet (1919) rendered them radio opaque by injection of 10% collargol into the worm 51. and superinfections were frequent. DEVELOPMENT OF DIAGNOSTIC METHODS The diagnosis of Guinea worm infection is usually obvious when the wor m makes it appearance in the ulcer. this first being shown by Billet in 1896 11.. but localization of living worms i s unsatisfactory as they are radiolucent. As in other systemic helminth infections. with Ramsay introducing an intradermal test in 1935 110 and a complement fixation test being described i n 1940126. Calcified worms may be seen on radiographs as shown by Connor 23 and by Dimier and Bergonie 25. saying that the uterus protruded through an opening just outside the circumoral ring o f papillae62.at the centre of the ulcer. A variety of immunological assays have been described.81 Manson believed that the worm pro lapsed a portion of its uterus an inch or two at a time through the mouth then it burst but Leiper denied this. Reddy and colleagues studied 10. at the same time watch the little hole. They found that multiple infections. some fluid exuded by the worm can be obtained and examined microscopically for the pathog nomonic larvae. If any doubt remains. both in 1918. Nearly two thirds of these people had had more than one attack. Patrick Manson in 1895 described the remarkable manner in which such a collection may be obtained: Squeeze a little cold water from a sponge so that the stream should fall on the sound skin within an inch or two of the guinea-worm ulcer. or a delicate tube will be protruded from it for an inch or more. thus suggesting that no immunity developed 113. the area of the whole. a former Britis h surgeon in Bombay described how one of them had removed a number o f worms from his own feet in 1861. and he had to leave them until the next day. Dick re marked that the native experts practised treatment along four lines . he applied heat and friction to make it yield its hold. when he got them out. Stinking the worm out with assafoetida poultices failed. then he dealt with the other. till he saw the white worm at the bottom. Many adapt a cataplasm [i. When he found the hook had been made use of. He had no experience of sucti on with the traditional trumpet-shaped sucking tube. a civil surgeon in Aden. passed the razor under it.stink the worm out. By raising almost invisible pieces of skin and tissue. and brought up a loop. a number of Indian soldiers infected with Guinea worm each con sumed more than a pound of sugar a day for three days. (It is certain that he was the host to th e worms that Bastian used in his description. but two (one in each foot) held on with their hooks. he merely legitimized the practice of many native barber-surgeons. then passed the eye of the needle (like a tentaculum) under it. but did not increase. and Bastian in turn stated that he had received his specimens from an infected Bombay surgeon via Harley). making an almost circular cut the size of a large pin's head. especially Avicenna an d Avenzoar.e. JW Reynolds. he deepened. He pulled on the two sides alternatively till he got one end out.116 In 1883. and this he winds little by little till the last part of the worm is drawn out. the injection of mercuric perchloride was recommended. had taught the following method: First the patient ties the end of the vein or nerve round a small piece of wood. while coaxing it out by prolonged immersion in running water was little mor e successful. Around 1895. most of them were extracted at one sitting.then summarized his ow n investigations.710 A History of Human Helminthology sixteenth century that the Arabian physicians. The sugar made th e . a poultice or plaster] or cold suffusion. suck it out and pull it out . claimed that electrolysis with a galvanic current was effective 35. In 1884. for Reynolds remarked that he later gave the worms to Harley. as near as he could guess. 9 Van Linschoten soon afterwards in 1596 provided the first known illustration of this process 73. then nearly a century later Velschius published a number of illustrations of the same procedure 133. the treatment may last many days before the sufferer is altogether free of pain and inconvenience. the centre of the worm. coax it out. to which Reynolds replied that galvanis m had been in use for at least 25 years 116. Most practitioners hoped that drugs would aid in the extraction of Guinea worms. A barber took five out of my legs very cleverly. and slicing them away with the razor. and snipped off a tiny bit of cuticle. Faulkner. but this did not find lasting favour. In doing this. As the structure is often three cubits long [1 cubit = approximately 50 cm]. but determined t hat many days of slow winding could be avoided frequently by incising the skin ove r the worm and then pulling it out by traction in the space of a few minutes 24. His stock of instruments consisted of a needle and a razor. In a review in 1880 of the treatment of Guinea worm in India. then he raised the skin over the centre of the worm with the point of the needle. A rather drastic method was tried in India in 1903. he commenced operations by finding. medinensis have been described in various animals .. In 1919. the Middle East and the Indian subcontinent. humans seem to be the only important host of this worm. as no trace of the metal could be found in the worm 56. he also showed that thiabendazole was useful in the treatment of 234 patients in the same country 108. Elliot claimed that injections of phenothiazine (which had recently been recommended for the treatment of enterobiasis) each week for four weeks assisted in the removal of worms 30. These occurrences became comprehensible with the demonstration that Guinea worm infection was transmitte d through the agency of a water crustacean. Two years later. Spanish . Hirsch (1885) wrote concerning thes e countries: All the authorities. He was uncertain whether the arsenic had a direct action on the worm. In 1942. Macfie (1920) though t that intravenous injections of tartar emetic (sodium antimony tartrate) recently introduced for the therapy of schistosomiasis had a beneficial effect 77.107. therefore. the disease fell to a minimum or disappeared altogether. Jeanselme gave three intravenous injections of novarsenobenzol to a young Senegalese soldier then a few days later a dea d worm was extracted. More recently. In 1970. but that its actio n differed from the other drugs because it killed the worm 123.Dracunculiasis 711 patient unbearably thirsty. it was prevalent in the Wes t Indies and parts of South America. Pardanani and Kothari found that metronidazole appeared useful 100. however.. that their effective ness was due to an anti-inflammatory action which facilitated the mechanical removal of the worms 95. arsenicals did not prove subsequently to be effective. but the dehydration made it easy to wind out th e worm unruptured 117. but Fairley and Liston later showed that the drugs had no action on either the adult worm or the embryos contained therein 34..48 The first person to draw attention to the infection in the Western Hemisphere appears to have been Don Diego Rodriguez de Valdes y de la Vanda. In former times. however. Although species of Dracunculus closely related to D. He concluded. but this therapy did not become generally accepted either. With the suppression of the slave trade. No significant advances were made until Raffier in 1965 showed that oral niridazole cured 70% of 71 patients on the Ivory Coast within seven days 106. UNDERSTANDING THE EPIDEMIOLOGY Many of the epidemiological observations o ver the past several centuries which led to the formulation of various theories on the mode of transmission o f dracunculiasis have been discussed.agree that dracontiasis was quite unknown before the importation of the negro. Muller then investigated the actions of these drugs and found that the worms appeared normal on histologica l examination and that the larvae developed normally in Cyclops. Shafei showed that mebendazole was effective in dracunculiasis. Dracunculiasis is now restricted to parts of Africa. When epidemics of dracunculiasis occurred. transmission took place during the dry season because the concen tration of Cyclops was reduced by the large volume and turbidity of wate r during the rainy season 69. most of them step wells. Water for drinking and washing purposes was obtained from the only well in the vicinity of the village. it is only in the last century that the reasons for the phenomenon have been understood. In contrast. Despite the clarity of his observations. in Iran where water is obtained fro m cisterns. it seems that transmission occurred for a number of years as evidenced. All that could be glea ned as to the cause of the outbreak of the disease was that men from a neighbouring village where dracunculiasis was rife the year before. however. Thus. fo r example. transmission occurred during the rainy season because water was then obtained from surface ponds rathe r than from deep wells 70. Thi s well had a flight of stone stairs down which the people descended to fill their pots with water. succeeded in infecting the local C. leuckarti and then producing an infection in a monkey. Fo r example. An ideal physical arrangement for the transmission of infection are th e stepwells so common in India. For uncertain reasons. He attributed the free dom of the country from indigenous infection to the habit of the inhabitants of drinking running rather than stagnant water15. had the habit of drinking from the well on their returning from th e fields.712 A History of Human Helminthology governor of Rio de la Plata in 1599 (Argentina/Uruguay) 98. the infection sometimes had significant economic effects. Chunder Dutt. used to go down into the well for drawing water whils t suffering from mature Guinea worms in their feet and legs. The importance of these wells was repeatedly recognized. Occasiona l exotic infections were imported into that country and Brug in 1930 from such a case. In the curren t outbreak. by the description by Ferg of an epidemic in Surinam in 1801 37. A similar situation occurred in the Dutch East Indies (Indonesia). were the e ffects on rural villages where a large proportion . an assistant surgeon at a colliery in Chonda in the Central Provinces of India. While such events have been recognized fo r many years. however. Rao reported in in 1942 that he had examined 434 wells and found that 158. India. it has bee n found that the incidence of infection has a seasonal pattern which some times coincided with the rainy season and sometimes did not. Mor e important. presumably because he had no access to recent literature reporting Fedchenko' s discovery. the infection appears to have now died out in these areas. In many endemic areas. Atten tion was drawn repeatedly to this by medical officers in charge of troops so afflicted in colonies in endemic areas. In some regions. who observed 180 cases in one village. This was recognized in 1879 by Mr. in Rajasthan. local habits and physical factors determining the distribution of infection throughout the year. he found that the field-labourers. descending one or two steps into the water to dip their hands o r water-vessels therein28. the precis e mechanism by which infection occurred was not apparent to him. to whom the infection was largely limited. contained Cyclops 112. the method o f purifying water adopted by Lind (1768) 68 has already been referred to. replacement of step wells by draw wells in a number of village s reduced greatly the incidence of infection 111. Leiper (1907 ) prophesied: it is evident that dracontiasis will disappear from the Coast towns when the provision of a properly-controlled water supply. In a part of India. with a consequent absence of dracunculiasis 64. they found that fish of the genus Barbus were a potent destroyer of Cyclops 89 A third approach has been to try chemical treatment of water. These efforts encompassed physical.62 The efficacy of such measures was shown in many areas. This concept was investigated in detai l by Moorthy and Sweet in India in 1936. permits the filling-in of the surface collections of rain water and the shallow wells upon which the natives now rely for their supplies. Another physical metho d suggested by Leiper was the heating of well water with steam. A number of chemicals have been suggested including potassium permanganate (1914) 131. wrote in 1905 that Cyclops can be removed readily by straining water through a fine handkerchief.Dracunculiasis 713 of the work-force were incapacitated temporarily. Leiper summarized the problem by remarking: "the isolation of infective man from healthy cyclops and o f infected cyclops from man must be the object of any organized effort to stamp out dracontiasis" 62. Leiper returned to West Africa and found that in certain place s Cyclops appeared to be kept under control by the innumerable small fish living in the water sources. for example. thus having a deleteriou s action on agricultural production. The elucidation of the central role of Cyclops in transmission provided solid ground for the evolution of control techniques. Since he did not believe that this was a practical proposition for the indigenous inhabitants. THE EVOLUTION OF PREVENTIVE AND CONTROL MEASURES Effective methods of avoiding Guinea worm infection were suggested by some observers even when the modes of transmission were understood only dimly. he advocate d structural alterations to existing wells to convert them into concrete trough s with conduction away of outflow water 44. 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Erfuti. cui accedit altera de vermiculus capillaribus infantium. Bulletins de la Société de Pathologie Exotique et de ses Filiales 6: 281-288 . Report of the Bombay Bacte riological Laboratory for the year 1912. 1928 121. Radiographie du ver de Guinée (filaire de Médine) après injectio n intrasomatique de lipiodol. 1919 132. ad mentem Ebnisinae sive d e dracunculi veterum. reptiles. Longmans. SOREL. 1913 130. 1912 . Berolini. 1937 129. VIIIth International Congress of Tropica l Medicine and Malaria. pp 217-225. Entozoorum synopsis cui accedunt mantissima duplex et indice s locupletissima. Report of the Bombay Bacte riological Laboratory for the year 1913. pp 51. presented by Major WG Liston. 1938 126. Sumtibus August Rücker. REICHARD CW. British Medical Journal i: 138. Cited in 3 133 VELSCHIUS GH. SHAFEI AZ. In. Revue d e Médecine et d'Hygiene Tropicale 9: 123-124. TURKHUD DA. ROLLESTON HD. pp 118-120. 1913 131. 1868 128. SINGER C. Annals of Tropical Medicine and Parasitology 6: 386-392. Exercitatio de Vena Medinensi. Preliminary report on the therapeutic effect of mebendazole in guine a worm infection. Augustae Vindelicorum. 1759 116. Bombay. Electrolysis in the t reatment of dracunculiasis. 1884 117. special number. Guinea-worm embedded for 21 years under the skin of the calf of the leg. Sketches of the natural history of Ceylon with narratives and anecdotes illustrative of the habits and instincts of the Mammalia. London. REYNOLDS JW. Specimens e xhibens novae versionis ex Arabico.Dracunculiasis 719 Parasitology 62: 399-406. TURKHUD DA. Note on Dracunculus medinensis (Guinea worm). Indian Medical Gazette 72: 606-609. Observations sur la biologie du ver de Guinée: infection intestinale des Cyclops. pp 14-16. Bulletins de la Société de Pathologie Exotique et de se s Filiales 21: 103-104. Bombay.. RICHARDS WG. Indian Journal of Medical Research. 1968 123. Dracunculose en Iran. Parasitology 14: 307-308. Note sur la durée de l'incubation du ver de Guinée. Government Central Branch Press. pp 456. Journal of Tropical Medicine and Hygiene 79: 197-200. fishes. Government Central Press. 1819 122. SOUTHWELL T. TENNENT JE. Republished as. STEFANOPOULO GJ. 1940 127. birds. Guinea worm. Annals of Tropical Medicine and Parasitology 32: 193-196. 1968 115. medinensis. SABOKBAR R. Proceedings of the Second All-India Sanitary Conference. 1674 134. 1912 125. ROUSSEL B. Transactions of the Pathological Society of London 43: 152. 1892 119. pp 32-36. presented by Major WG Liston. Some observations on guinea worm larvae. On certain early referen ces to dracontiasis. Réaction de fixation du complément et intra dermo-réaction au course de la fila riose humaine à Dr. ROUBAUD E. insects etc. RUDOLPHI CA. cum commentarion uberiori. the guinea-worm disease. 1976 124. and a description of the modes of capturing and training it. 1914 . WURTZ. Dissertatio de pediculus inguinalibus insectis et vermibus homin i molestis. de VEIGA T. Tehran. Theophili Goebelli . 1913 120. pp 811. 1912 . including a monograph of the elephant. TREWN HS. Mechanical extraction was practised Rudolphi described the larvae (embryos) of Dracunculus Jacobson rediscovered the first-stage larvae Bastian made a detailed description of the anatomy of the adult female worm Fedchenko observed that embryos developed with the body cavity of the crustacean .1. stimulated the activation of larvae and their release from Cyclops Leiper fed infected Cyclops to monkeys and recovered 3 immature female and 2 small male Guinea worms at autopsy 6 months later Turkhud administered infected Cyclops to 5 volunteers.720 A History of Human Helminthology Table 26. simulating gastric juice. Landmarks in dracunculiasis ___________________________________________________________________ BC 1819 1834 1868 1869 1880 1892 1894 1906 1906 1914 1937 1956 1965 1967 1970 1976 Guinea worms have been known since antiquity in endemic areas but their nature was controversial. Cyclops Mackay described an epidemic of dracunculiasis in Indian troops and suggested that the incubation period was 8-12 months Charles claimed to find male adult worms in the retroperitoneal tissues at autopsy Manson confirmed Fedchenko's observations on development withinCyclops Leiper showed that hydrochloric acid. one person developed dracunculiasis one year later Moorthy provided the first detailed account of the male adult worm Onabamiro studied the route of migration of parasites in experimentally infecte d animals Raffier showed that niridazole assisted the extraction of worms Raffier showed that thiabendazole assisted the extraction of worms Pardanani and Kothari reported that metronidazole assisted the extraction of worms Shafei claimed that mebendazole kills Guinea worms ___________________________________________________________________ . ceylanicum. INFECTION WITH ANCYLOSTOMA SPECIES A. it was renamed Anatrichosoma cutaneum by Chitwood and Smith 67. which stretches in a convoluted manner across the side. A human case of creeping eruption of the skin due to infection with this worm was reported by Morishita and Tani in Japan i n 1960225. with the eventual acceptance that they were different specie s (see chapter 20). duodenale. and during the last three weeks has travelled across to the left. Contrary to A.. reddish.. Boots and Miller in 1922 and name d Trichosoma cutaneum 327. it became known as Ancylostoma braziliense . BRAZILIENSE This parasite was first recovered from the intestine of dogs and cats b y Gomes de Faria in Brazil in 1910 who called it Ancylostomum braziliense 130. much resembling to the touch what would be produced by a bristle underneath the epidermis. braziliense does not complete its development in humans.It was said to have begun as a fine line on the right ankle. although the worm involved in that particular case will never be precisely known: The morbid appearance consists of a fine line on the left side of the abdomen. A. With the acceptance of Ancylostoma as the generic name for this group o f hookworms. slightly-elevated line. which gradually travelled up the thigh on to the abdomen.Chapter 27 NEMATODE INFECTIONS IMPORTANCE OF LESSE R INFECTION WITH ANATRICHOSOMA CUTANEA This Capillaria-like parasite of the skin and nasal mucosa of monkeys in Asia and Africa was discovered by Swift.172 The anonymous reporter in The Lancet who wrote the above also commented that this was: 721 . In 1958. A. It appears to consist of a narrow.. there was controversy concerning the relationship between this worm an d A. ceylanicum and Necator americanus. This syndrome appears to have been first described by Robert Lee in an address to the Clinical Society of London in 1874. but it is the major cause of the clinical syndrome called cutaneous larva migrans. where it was at first in the right side. For many years. In 1892. CANINUM This hookworm parasite of dogs was first described by Ercolani in 1858 a s Sclerostoma caninum 105. and sometimes continuing for weeks or months 97. that it has completed its development in humans. they named it Agamonematodium migrans pending the discovery of the adult worm 162. the nature of which had given rise to much diversity of opinion amongst those who had seen it. then this was confirmed by Shelmire wh o infected 18 volunteers experimentally 303. Burks and Kingery believed tha t chloroquine was valuable 48 but it was supplanted by thiabendazole when th e efficacy of this drug was demonstrated by Stone and Mullins in 1965 321. saw a similar case and. In 1895. the condition was treated. The histological sections were submitted to Ransom at the US Bureau of Animal Industry and he gave the guarded opinion that they were third-stage larvae of the super-famil y Strongyloidea. Smith claimed that antimony (Fouadin) was effective in a child with multiple infections 309 but Blank could not confirm this observation 40. for Dove (1932) reviewed 301 cases in Florida and showed that the lo wer limbs were afflicted in 76%. Muhlesein reported that eventually the cutaneously-migrating larvae may pass to the deeper tissues and cause pneumonitis 228. proposed the term "creeping eruption" 80. The distribution of infection on th e body noted many years before by Lee was typical. braziliense as the cause of the condition by studies in animals and by applying A. Crocker also in England. the hand and arms in 14% and the trunk in 9% of cases. There have been several claims. Initially. Florida and saw 179 cases in the space of ten days. was one cause of this condition 292. Kirby.346. Samson-Hammelstjerne showed that the larva of the fly. then renamed Ancylostoma caninum by Hall in 1913 135 . and on which there was not much light thrown by the members of the Society.722 A History of Human Helminthology a remarkable case of Skin Disease in a child. each one moving only several millimetres per day. White and Dove then implicated A. Severa l workers have shown that this worm does not usually cause cutaneous larv a migrans in humans although it might cause ground itch 149. More than half o f these patients were thought to have acquired their infection at the beach. A. by freezing o r cauterizing the skin overlying the advancing larva. In 1953. 13 and concluded that a commission had been appointed to investigate the cause. braziliense larvae to human skin experimentally 345. usually with success. He noted that movement of the larvae was very slow.Smith and his colleagues held a clinic in Jacksonville. A larval nematode was seen in skin biopsies. Gasterophilus. In 1943. suspecting that an insect larva may be the cause. beginning with Manalang in th e Philippines199. . The disease was particularly prevalent in the southeastern United States of America and in 1926. The first infection in a human was repo rted by Nomura and Lin (as Haemostrongylus ratti) in Taiwan in a 15 year old boy with suspected meningitis from whom six young adult worms were identif ied in the cerebrospinal fluid. By 1979. Most human infections are thought to have been acquired by ingestion of undercooked specimens of the giant African land snail. Many species of slugs and several species of lan d snails as well as a planarian. worms have been visualized in the eye. Dougherty transferred it to the genus Angiostrongylus of Kamensky158 naming it Angiostrongylus cantonensis 96. The circumstances surrounding the implication of A. 259 cases were known to have occurred in Taiwan 63. the infective larvae migrated to the brain and moulted twice. but this report was buried in the Japanese literature for many years 28. worms have been found in human lung355. The larvae then infected a molluscan intermediate host within which they became infective larvae in about two weeks.286. Occasionally. cantonensis in this condition have been a subject of recent controversy8. either in the anterior chambe r or vitreous 260. but patent infections with production of eggs and excretion of larvae have not been reported thus far. China and named it Pulmonema cantonensis 64. Achatina fulica.238. In 1946. ANGIOSTRONGYLIASIS ANGIOSTRONGYLUS CANTONENSIS In 1935. most cases having an incubation period of about three weeks and being relatively mild in severity and self-limiting in duration. Chen recovered thi s worm from the respiratory tract of a rat caught in Canton. MALAYANUM 723 This hookworm was first recovered from a bear and described as Helarctos malayanus by Alessandrini in 1905 7. crabs. The diagnosis is best made by recovery . The y reported that eggs hatched in the lungs of the rodent host then the larva e migrated up the trachea and were swallowed then expelled in the faeces. The generic name is derived from a combination of the Greek words (ANGEON) and (STRONGYLOS) meaning "vessel" and "round".Miscellaneous Nematode Infections A. respectively. The first well-documented fatal case in a human was reported by Rosen and hi s colleagues in 1962287 following the investigations of Rosen into the cause o f eosinophilic meningitis in Tahiti and Hawaii. fresh-water prawns and frogs have bee n found infected with third-stage larvae. The worm is a common cause of eosinophilic meningitis. The young worm s about 2 mm long. The life cycle was first described by Mackerras and Sandars in Australia in 1955. these non-molluscs serving as paratenic hosts. Rarely. When ingested by the definitive host. then migrated to the lungs and began laying eggs about four weeks after infection 196. Infection in humans has been reporte d once357. headache often being relieved by removal of cerebrospinal fluid at lumbar puncture. began to lay eggs which hatched with larvae appearing in the faece s about three weeks after infection 221. In histological sections of these and other resected tissues. The m ain features were pain in the right lower quadrant of the abdomen. the larvae were freed from the digested mollusc and migrated into the lymphatics of the gut mucosa. COSTARICENSIS In 1967. Chabau d erected a new genus. the rats Sigmodon hispidus and Rattus rattus 220. Morerastrongylus. and he and Ash recorded the finding of infective larvae in the tissues of the slug Baginulus plebeius 222. The mode of infection in humans i s . Since then. it has been suggested that killing the worms could exacerbate the inflammatory reaction with undesirable consequences in infected patients . ingested by the slug intermediate host. Alicata and Brown were of the op inion that skin testing was useful in ruling out the diagnosis but that a positive reaction could not be relied upon because of cross-reactivity with other helminths 9. to house this worm 54. In 1973 . portions of a worm were found and eggs were seen in the midst of a granulomatou s inflammatory reaction and eosinophilic vasculitis. Céspedes and colleague s believed the worm to be a metastrongylid parasite of mammals which ha d infected humans by accident 52. When the infected slug was eaten by a rat.53 In 1971. moulted twice. In any case. but Anderson in 1978 reduced it back to Angiostrongylus 11. many other species of mammals have been found infected and human infections have been recorded from other parts of Central and northern South America. Morera reported the discovery of the adult worms in natural definitive hosts. although a precipitin test has been described recently by Sauerbrey 297. In the following year. Larvae are not discharged in the faeces of humans although eggs and larvae may be seen in specimens of bowel. which reached 2-4 cm i n length. first stage larvae were passed in the faeces of an infected rat. Treatment is largely symptomatic. the n migrated to its mantle and foot and moulted twice to become infective after two to three weeks. but did not seem to be effective in humans 152. Also in 1971. Worms have been removed surgically from the eye. then migrated to the ileocaecal region where they entered th e arterioles and small arteries and the adult worms. Céspedes and his colleagues published two papers describing th e clinical features and pathology of an illness which had been seen in 31 patients in Costa Rica between 1952 and 1967. Th e diagnosis is therefore generally made by biopsy. Thiabendazole was reported as being active against these worms in experimental animals 82. A. Two yo ung children died from perforative ileitis.724 A History of Human Helminthology of the worm. Morera described the life cycle of the worm. Morera and Céspedes described the causative worm which they named Angiostrongylus costaricensis 223. often associated with a palpable mass and with an eosinophilia ranging from 8-60%. simplex by Davey in his revision of the genus 91. identified at that time as Eustoma rotundatum. which had been acquired by ingestion of slightly salted herring. It was renamed Thominx aerophila by Dujardin in 1845 99 then transferred to the genus Capillaria of Zeder359 by Travassos in 1915 to become Capillaria aerophila 333. Dujardin erected the genus Anisakis to house certain species o f nematodes found in the stomach of marine mammals 99. The identification of thes e worms was changed to Anisakis marina by van Thiel 330 then altered to A. It is now known that when eggs of these worms are passed in the host's faeces. Later in tha t year. after six week or so they become infective and infection of a new host occurs after their ingestion . They may be consumed accidentally or possibly larvae may leave the slug in the mucus and thus contaminate fruit and vegetables. they tend to migrate to the muscles 310. ANISAKIASIS In 1845. In 1960. The generic name is derived from the Latin word "capillus" meaning "hair'. The freeliving larvae may be ingested by shrimp-like crustacean s (Euphausiidae) in which they develop int o infective larvae. The infective larvae may in turn be eaten by fish and squid in which they migrate into the peritoneal cavity and tissues.Miscellaneous Nematode Infections 725 uncertain since raw slugs are not generally eaten in endemic regions. Rodenburg and Wielinga 284 and Kuipers and colleagues 167 in Holland described an acute abdominal illnes s in humans due to inflammation of the small intestine caused by larvae. swallowed and discharged in the faeces. one patient developed peritonitis and two patients died 331. CAPILLARIASIS CAPILLARIA AEROPHILA This common parasite of the respiratory mucosa of cats. more than 500 cases had been recorded there 358. they embryonate and hatch in the water and the free-swimming larvae may survive for up to thre e months 138. Treatment with thiabendazole has been recommended by Loria-Cortes and Lobo-Sanahuja 189. foxes and some other carnivores in many parts of the world was found in a fox and described as Trichosoma aerophilum by Creplin in 1839 78. The eggs ar e coughed up. porpoises and dolphins and embed in the gastric mucosa of these mammals to produce tumours 330. The infection was first recognized in Japan in 1965 by Asami and colleagues 16. van Thiel and colleagues report ed 11 such cases. after death of the fish. in most of whom worms were discovered at laparotomy for relief of intestinal obstruction. dogs. . By 1979. The infective larvae may then be transferred from fish to fish and are finall y eaten by whales. especially rats. The first case in humans was reported by MacArthur in India in 1924. where it is now considered to lie. This patient responded to treatment with diethylcarbamazine. often in patients who have presented with hepatomegaly and eosinophilia 246. multiple abscesses were found scattered widely in both lungs and in the liver. The diagnosis is made by finding eggs in sputum or in faeces. In 1916. Nishigori showed that after ingestion of eggs. Hall erected the genus Hepaticola and transferred it to this genus naming i t Hepaticola hepatica 136. hepatica eggs were found microscopically in close proximity to the liver abscesses 194. Transmission occurs between carnivorous. Travassos had placed it in the genus Capillaria of Zeder359. Masses of C. C. presumably the ova had been ingested and passed directly through the alimentary tract 116. the adult worms produced eggs which were deposited in the liver parenchyma and were not normally excreted in the faeces 237. though one patient was diagnosed after finding the worm in a lun g biopsy. either at autopsy or by finding eggs in the liver biopsies .304. these may then b e ingested in food. however. At the post-mortem examination of a 20 year old Br itish soldier who had died from pneumonia. thia bendazole and corticosteroids 6. When deposited on damp soil. especially canna balistic animals. In the preceding year. but has also been found in many other species of mammals in all continents. larvae passed to the liver. th e eggs passed through the gut and were excreted in the faeces. the eggs sometimes remained viable for about two years 334. spurious instances of infection have been reported after finding eggs in the faeces 306. but this may have been coincidental 76. Occasionally. the first documented cases being reported in th e USSR by Skrjabin and his colleagues in 1957 308. The most common clinica l manifestation is asthma. HEPATICA This worm was discovered in the liver of a mouse in Australia in 1893 b y Thomas Bancroft who named the parasite Trichocephalus hepatica 18. they developed into the infective stage. mainly via the portal system a nd matured over four weeks or so. so the correct name is Capillaria hepatica 333. eggs of a Capillaria species were found in the faeces of a man who had been admitted to hospital in the Philippines with malabsorption syndrome. C. The parasite is common in rodents . PHILIPPINENSIS In 1963. He died three days later and autopsy revealed worms in the small and larg e . two children treated wit h antimony recovered. Infection has since been diagnosed in a number of humans. Effective treatment has not yet been devised. Although the adult worms soo n died. When the infected liver of the host was eaten by a predatory or scavenging animal. drink or soil 352.726 A History of Human Helminthology Infection in humans is rare. an illness causing seve re disease and sometimes death was reported in Ilocos Sur Province of the Philippines. The infection was thought to have been acquired by eating imperfectly cooked fish in the Baltic. Schaum and Müller described larvae.90. In 1967. the adult worms together with larvae and eggs have been found in the small intestine. identified as Contracaecum osculatum . It was shown that eggs passed in the faeces required almost two weeks to embryonate and tha t development to the infective larval stage in the fish intestinal mucosa took at least three weeks 35. In humans. Whalen and his colleagues showed that thiabendazole was partially effective in intestina l capillariasis344. INFECTION WITH CHEILOSPIRURA SPECIES This genus was erected by Diesing in 1861 94. a focus of infection was discovered in Thailand 256. Cross and his colleagues indicated that monkeys had been infected experimentally by feeding the m freshwater fish and suggested that autoinfection may occur 81. and naming the parasite Capillaria philippinensis 69. In 1967. INFECTION WITH CONTRACAECUM OSCULATUM In 1912. Valesquez and Salazar in the following year describing the adult worms. then Singson and co-workers found that mebendazole wa s considerably more effective 305. especially the jejunum. INFECTION WITH CYCYLODONTOSTOMUM PURVISI This hookworm parasite of the large intestine of rats was described by Adams in Malaya in 1933 2. Cure was obtained wit h thiabendazole 298. Railliet and Henry raised the genus Contracaecum to house certain species of nematode parasites of reptiles and fish 275. Infection in a human has been reported once 34. This led to Chitwood.81.Miscellaneous Nematode Infections 727 intestines68. In 1973. and in heav y infections a severe enteropathy with malabsorption and wasting is produce d which not infrequently leads to death in a few weeks to months 50. The worm has been recovere d once from a human. it was found in a conjunctival nodule in a Filipino farmer 4. subsequent investigations revealed Capillaria eggs in the stools of most patients 49. 3-4 mm long. . In 1972. in an eosinophilic granuloma in the intestine of a patient in Germany who ha d symptoms of peritonitis. In 1901. Collet-Meygret called it in a vernacular fashion. Only a small number of humans have been infected with this worm which measures up to a metre in length and is ab out 5 mm in diameter. commonly known as the giant kidney worm. Stiles argued that it should b e called Dioctophyma renale 318. 1941). .728 A History of Human Helminthology INFECTION WITH DIOCTOPHYMA RENALE This parasite. Most proven cases have bee n diagnosed at autopsy or a worm has been expelled through the urethra. Eggs are excreted in the urine and are ingested by aquatic oligochaetes in which they develop to the infective larval stage. These parasites may have been D. although Küchenmeister comes to the conclusion that it has never been met with. was known t o Redi279 but was described by Goeze in 1782 and called Ascaris renalis by him126 . INFECTION WITH DIPETALONEMA SPECIES The genus Dipetalonema was erected by Diesing in 1861 94. Sprenti described by Anderson in 1935. It was known by this designation for many years. Immature worms have been found in humans on several occasions including in an arm nodule 27 and in the eye26. Owen and Hennessey in Uganda reported the presence of small yellow nodules in th e bulbar conjunctiva together with proptosis and periorbital oedema in som e patients247. a dioctophyme 77. arbuta described by Highby in 1943143 or D. Mammals can be infecte d directly by ingestion of infected oligochaetes. but more commonly they ar e taken up first by amphibia or fishes which are in turn ingested by the definitive host197. but they may have been Dipetalonema or Mansonella parasites 25. In 1932. In 1802. Poltera255 considered that these were Loa infections. 23 Blanchard reviewed the literature in 1886 and regarded only nine human cases as authentic. Rudolphi in 1802 labelled it Strongylus gigas 289 then in 1851 Diesing renamed it Eustrongylus gigas 93. Goeze's specimen was recovered from a dog but the worm has sinc e been found in many carnivores. One of the first presumptive cases reported in the Englis h literature was described by Cannon in 1887 51. and despite some opposition. In 1860. Beale in his review of parasitic infections of the urinary tract wrote: The parasite appears to have been found in the human kidney on one occasion. The specimen is preserved in the College of Surgeons. On e case has been reported in which an immature worm was identified in a nodule on the chest wall 30. his view eventually prevailed when it was endorsed by the American Society of Parasitol ogists in 1941 (Journal of Parasitology 27: 279. it thus becoming known a s Dirofilaria immitis. D. TENUIS This parasite of the cutaneous tissues of the raccoon in the United States o f America was described by Chandler in 1942 59. tenuis 241. a worm was recovered from a subcutaneous nodule near the eye 307. worms have been lodged in a branch of the pulmonary artery and many have been found by a routine chest X-ray70. Yokogawa found D. Many infections of the eye or eyelid reported from the USA as due to D. D. It is transmitted b y mosquitoes including Anopheles maculipennis 131 and Culex quinquefasciatus (= fatigans)19. coronata in the urine of an elderly patient 356. The generic name is derived from a combination of the Latin words "dirus" and "filarium " meaning "cruel" and "ball of thread". The microfilariae reported in dog blood by Gruby and Delafond in 1843 132 and later named by them Filaria papillosa haematica canis domestica 133 may have been D. respectively. In most cases since then. It is transmitted by mosquitoes such as Aedes aegypti . Chandler observed this species in the stomach contents of 9 achlorhydri c patients58 who had presumably ingested them in decaying vegetable matter. In a number of other patients. Human infection was first reported b y Skrjabin and his colleagues in the USSR in 1930. They have rarely been found in the abdominal cavity 328.341 . In 1911.Miscellaneous Nematode Infections INFECTION WITH DIPLOSCAPTER SPECIES 729 This genus was erected by Cobb in 1913 73 to house certain species of free living worms which live in decaying organic matter. and subcutaneous tissues 37. the worms have presented as subcutaneous tumours (reviewed in 115). Raillet and Henry 272 erected the genus Dirofilaria and transferred the parasite to it. REPENS This parasite of the subcutaneous tissues of dogs was described by Railliet and 33 Henry in 1911274. the eye95. DIROFILARIASIS DIROFILARIA IMMITIS This worm was found in the heart of a dog and described as Filaria immitis by Leidy in 1856 in the United States of America 173. immitis 340. . Faust and his colleagues first described this in 1941 following the discovery of a worm in the vena cava of a woman in Ne w Orleans111. Occasional infections have occurred in humans with incomplete development of the worm. conjunctivae may have been really due to D. however. Humans are infected very rarely. Prommas and Daengsvang in Thailand reported that they had shown experimentally that Cyclops was the first intermediate host. Mitter found the parasite in a cat. are parasites of the anterior gut o f fish-eating birds. respectively. He erected a ne w genus. conjunctivae infections reported from Europe and Asia may in fact have been D. The vectors are simuliid blackflies. migrating larvae may be found in the tissues of mammals that have eaten infected fish. The first human infection sus pected as being due to this parasite was removed from the breast of a woman in Washington State. Several years later. The infective larvae develop in small fish and amphibia i n which they may reach up to 10 cm in length. repens infections. Thre e fishermen in the United States of A merica swallowed live bait minnows and all developed severe abdominal pain. Almost 100 years were to pass before inroads were made into an under standing of the life cycle of this worm. two required operative intervention t o remove worms migrating into the peritoneal cavity 134. Gnathostoma. GNATHOSTOMIASIS GNATHOSTOMA SPINIGERUM This parasite was discovered by Richard Owen in 1836 in the stomach wall of a tiger which had died in the London Zoological Gardens. In 1933. In 1912. th e larvae forced their way into the body cavity of the copepod and moulted after . spinigerum eggs obtained from an infected cat and observed spontaneous hatching of larvae142. dog and leopard 212. D. Heydon described the development in water of G. United States o f America342. then Chandler in 1925 reported finding the worm i n 10-30% of cats examined post-mortem in India 56. the specific epithet reflects the rings of spines on the parasite's head 248. INFECTION WITH EUSTRONGYLIDES SPECIES Adult worms of various species of the genus Eustrongylides. derived from a combination of the Greek words (GNATHOS) and µ (STOMA) meaning "jaw and "mouth". Unencapsulated. He also noted finding encysted larvae in the mesentery of Indian snakes (rock python and cobra) 57. URSI This parasite of the subcutaneous tissues of bears was described by Yamaguti in 1941353 and was reviewed by Anderson in 1978 10. to house this species which he named Gnathostoma spinigerum . which was erected by Jaegerskiöld in 1909 151.730 A History of Human Helminthology Many cases of D. Rana rugulosa. but that the larvae only matured to the adult stage in the stomach of dogs and felines after a migration through the tissues 213. but also via the mucous membrane of the oral cavity 283. In Thailand. fish and many mammals that had eaten fish flesh. When the freshwater fish. either causing an abscess 204. by Railliet in 1893 263. swellings continued intermittently for another ten years until a second worm was extracted. In 1945. amphibia. spinigerum from the stomach nodule of a presumably "clean" cat which had been fed larvae obtained from an infected fish. The various hosts of infective third-stage larvae. Ophiocephalus striatus and Clarias batrachus. the second-stage larvae escaped and migrated to the tissues where they moulte d again to become infective third-stage larvae 258. reptiles. Glossobius giurus 5. that they examined86. spinigerum by Leiper180. Monopterus albus. is enjoyed frequently 214. The first human infection with this parasite was described by Levinson in 1889. often through the skin. I n one patient who had transient swellings for seven years and then had a worm removed from an abscess in his right hand. or migrating through the subcutaneous tissues producing a form of cutaneous larva migrans 142. probably including man. respiratory tract and urinary tract. The worm was remove d from an abdominal tumour in a Thai woman by Dr Deunzer in Bangkok and forwarded to Levinson who named it Cheiracanthus siamensis 183. The worm often attempts to extrude itself. The larvae may migrate throughout the huma n body. while in Japan.Miscellaneous Nematode Infections 731 10-14 days to become second-stage larvae 257. the sliced raw flesh of animals or fish. siamense. They then completed the lif e cycle experimentally by infecting cats with infected fish 259. crabs. then recovered adult G. a paratenic host) 84. many living infective larvae are found in a kind o f fermented food made from the raw flesh of freshwater fish which is a favourite dish of Thai women 83. may become infecte d either by ingestion of infected Cyclops or by the consumption of anothe r infected vertebrate (i. Mukerji and Bhaduri reported the extraction of a worm from the anterior chamber of a n . Clarias batrachus. They were unable to infect cats with infected Cyclops but showed that a second intermediate host was required.e. and was then shown to be synonymous with G. It was transferred to the genus Gnathostoma. "sashimi". Miyakazi indicated in 1954 that he had found infective larvae i n crayfish. but which seems to have been published somewhat later since it did not arrive at the Bureau of Hygiene and Tropical Diseases in London until 17 March 1938) that they had found encysted gnathostome larvae in the flesh of three species of naturally-infected freshwater fi sh. Their presence may become manifest when they appear superficially . Daengsvang and Tansurat i n Thailand then showed that natural inf ections occurred in over 90% of the frogs. Africa and his colleagues in the Philippines then re ported (in a paper dated October 1936.293. and 30-40% of the freshwater fishes. 80% of the eel. ingested infected Cyclops. Humans are thought to be usually infected by eating poorly-cooked infected fish or domestic birds (ducks an d chickens).329 or migratory oedema 283. Maplestone and Rao thought it likely that the worm had lived for 17 years 205. becoming G. has been shown to be effective against migratin g larvae in cats 85. The definitive host becomes infected by swallowing an infected insect 22. About 30 human cases have now bee n reported. The first fatal case recorded was described b y Chitanondh and Rosen in 1967. In 1898. a compound not available for human use. lives in the mucosa an d submucosa of the oral cavity and oesophagus of animals. Effective chemotherapy has not yet been demonst rated although ancylol. Ward described the extraction of a worm from beneath the mucosa of the lower lip of a 16 year old girl. Cobb erected the genus Haemonchus and transferred this parasite into it. the worm thus becoming known as Haemonchus contortus 72. INFECTION WITH GONGYLONEMA PULCHRUM This consmopolitan parasite of ruminants was first described by Molin i n 1857 215. HISPIDUM This parasite found in the stomach of pigs was described by Fedchenko i n 1872112.732 A History of Human Helminthology eye229. When the parasites migrate through the deeper tissues. INFECTION WITH HAEMONCHUS CONTORTUS In 1803. Most worms have be en found in the buccal cavity or its environs. may be valuable 214. The adult worm. It rarely infects humans 224. a Thai woman developed a progressiv e ascending paralysis and a worm was found in the spinal cord at autopsy 65. up to 6 cm in length. Larvae may also migrate through the brain to produce an eosinophili c meningoencephalitis 47. The generic . the patient had stated that she had seen the worm on three occasions during its migratio n between the lips and the fauces 339. Treatment is by surgical removal. then the same patient seems to have b een described by Sen and Ghose 302. The diagnosis is made by recovery of the worm but immunoassays. Eggs are passed in the faeces and ingested by dung beetles or cockroaches. particularly skin tests. they may produc e visceral larva migrans. Rudolphi described Strongylus contortus as a parasite of sheep 290. anthelmintic therapy is uncertain.261. The first human infection was recorded in Italy in 1864 by Pane who called the worm Filaria labialis 249. In 1916. The name is derived from a combination of the Greek word s (GONGYLOS) and µ (NEMA) meaning "round" and "thread". The worms have been removed surgically. G. respectively. they hatch in the intestine and the larvae burrow into the body cavity and encapsulate. but Feng and colleagues have recorded one patient w ith oesophageal localization 114. Mornex and colleagues have recently reviewed human Mammomonogamus infections and indicated that 78 cases have been reported. West Indies of a male and female worm which were coughed up by a woman. Hoffman in 1931 recounted removing a red object from the posterior wall of the pharynx of a patient who had had a continuous cough since visiting a farm several weeks previously. and (ASKARIS.171. 1899 45. (CHEILOS). respectively. In most instances it has been recovered from th e tissues of the head and neck with colonies of adult worms. this reflects the deep median depression in each lip which gives the parasite the form of a harelip. a fatal case of encephalitis has been described285. with a chronic cough . Variable success has been achieved with diethylcarbamazine 98. In 1948. Kingi to be synonomous with S. Leiper named the parasite Syngamus Kingi 179. commonl y known as "gapes" was recovered from an ox and described by Railliet in 1899 who named it Syngamus laryngeus. Lucia. eggs and larvae in various stages of development being found in abscesses or nodules whic h develop over months or years 42. INFECTION WITH MAMMOMONOGAMUS LARYNGEUS This parasite of the upper respiratory tract of cattle and felines. The name is derived from a combination of the Greek words (LAGOS). respectively. Recently.239 and levamisole 42.180. The life cycle of this worm is uncertain. This worm has not yet been identified i n animals and the life cycle is uncertain. laryngeus in copula 144. although Buckley believed S. de Magalhaes recorded the infection once in Brazil 198 and Sweet described the infection in three aborigines in Western Australia 326. it proved to be a pair of M. mostly from Central America and the Caribbean 226.Miscellaneous Nematode Infections 733 name is derived from a combination of the Greek words µ (HAIMA) and (ONCHOS) meaning "blood" and "spear". nasicola von Linstow. ASCARIS) meaning "hare-lipped" and "worm" . Rizhikov transferred the worm to the genu s Mammomonogamus 282. It was later considered to be synonymous with M. Leiper recorded the discovery by King in St. INFECTION WITH LAGOCHILASCARIS MINOR This species was first described by Leiper in 1909 who received the specimen obtained from a human infected in Trinidad 177. Infection i s rare in humans. laryngeus. . In 1913 . thiabendazole 217. The infection has been reported i n humans a number of times. the specific epithet reflecting its location in the host265. demarquayi" 88. the blunt-tailed form was indeed F. I do not feel justified in giving the measurements of the dried organisms.734 A History of Human Helminthology MANSONELLIASIS MANSONELLA OZZARDI For a number of years. however. In 1897. but in 27 of them he discovered tw o different microfilariae: One of these minute filariae closely resembled filaria Demarquayi of St.202 CW Daniels in British Guiana. the other closely resembled.this new filaria of Demerara. colonial assistant surgeon in St. it has yet to be decided whether it is a new one or the f. perstans. it exhibits no diurnal periodicity whatever. the only specimens available. but from reasoning that is difficult to follow . He noted considerable variability in size of the F. is naked in the blood .. the dimensions may be materially altered. West Indies. Manson found no evidence of W. Filaria sanguinis hominis (= F. Vincent. Manson found microfilaria bancrofti. in which he concluded that there were another two species of human filariae 202. Otto Galgey. nocturna = Wuchereria bancrofti) was well-known and Manson himself had described two new species. Filaria Demarquayi has no sheath. Patrick Manson in London corresponded with friends and acquaintances all over the w orld in an endeavour to collect statistics on the various species of filariae. and after comparing them with specimens o f . Lucia. In 1893 and again in 1895. being present in the peripheral blood both during the day and during the night. Lucia. like filaria perstans.. being minute and sharp-tailed and without a sheath. demarquayi he had found in St. wrote: I do think the sharp-tailed Demerara filaria is a new species and not identical with filaria Demarquayi. filaria perstans a parasite which hitherto I had found only in West African blood. . but in ten of them he discovered: an entirely new filaria which at Blanchard's suggestion. bancrofti infection. if it was not identical with. microfilaria diurna (= Loa loa) and microfilaria perstans (= Mansonella perstans) in 1891. suffice it to say that filaria Demarquayi is less then half the size of filaria nocturna. as in consequence of the shrivelling the parasites have undergone. Dr Newsham of St.. Vincent. but. West Indies. was even more forthright.I propose to call provisionally filaria Ozzardi. was less certain. I have named filaria Demarquayi.Demerara bein g a town in British Guiana)...202 In early 1897.202 Manson decided that of these two microfilariae (which he referred to a s "Demerara filaria" . he presented his findings to the annual meeting of the British Medica l Association held in Montreal. Canada.. for one year later he reported to the British Medical Association: "If the sharp-tailed embryo s represent another species. had sent him a large number of blood films prepared from residents of that island. In six o f them. This new filaria is shaped exactly like filaria nocturna and filaria diurna but is very much smaller. Dr Ozzard in British Guiana (Guyana) had sent Manson 6 3 slides prepared from people living in the interior of that country. they omitted M. In 1902. however. that is to say. Dominica and St. Vincent and microfilaria ozzardi from British Guiana.Miscellaneous Nematode Infections F. this parasite was also later shown to be synonymous with microfilaria ozzardi 337. and had concluded that they were identical 190. Ozzard was not able to come to any definite conlusion. ozzardi concluded that they were one and the the same worm: 735 I am inclined to believe that all are filaria Demarquayii. C. Vincen t indicated that microfilaria ozzardi was taken up by and developed in gnats of the genus Culicoides 45. In 1933. When Chabaud and Bain reclassified the Dipetalonema group in 1976. but owing to imperfections in the specimens. 120 In 1899. had priority 180. Lucia. Lucia. with this parasite as the type and only species 108. Vincent. Faust erected the genus Mansonella in honour of Manson. to differentiate this from the other described adult filariae. while the . Low in 1901 attempted to determine the vector of the parasite by exposing infected patients to Culex fatigans (= quinquefasciatus). Biglieri and Araoz found a microfilaria in persons living in the province of Tucumán in northern Argentina. Leiper pointed out. juncea 266. F. however. taeniatus and Anopheles albipes. and that discovered by me in St.89 Later that year Galgey found two parental forms of F. Buckley in St. Nelson and Davies showed that C. I consider. phlebotomus was a vector in Trinidad 231. In 1929. ozzardi as they considered it insufficiently known for taxonomic consideration 55. He sent them to Ozzard i n British Guiana for identification. Stegomyia fasciata (= Aedes aegypti). comparing them with F. ozzardi were synonymous. but found that they were refractory to infection. In 1914. Daniels reported finding an adult female worm and a portion of a n adult male worm which differed from the adult F. and named it microfilaria tucumani 36. furens 46. Since this name had already been used for W. ozzardi. but with negative results 190. Subsequently. In 1982. With the recognition that F. Orihel and Eberhard redescribed the species and redefined the genus using materia l obtained by infection of experimental monkeys ( Erythrocebus patas)242. The name 'Filaria Ozzardi' might be retained for the new species. Railliet proposed the designation F. perstans and concluded: The differences observed both in the male and female are sufficient. bancrofti by Zune361. Many years later. They were foun d lying free in the subperitoneal connective tissues of the anterior abdomina l wall. bancrofti and F. he caught and dissected a variety of blood-sucking insects feeding on inhabitants in a heavily endemic area o f British Guiana. and the sharp-tailed form of filaria Ozzardi (British Guiana) are identical. the correct name appeared to be Filaria demarquayi since Manson had described this parasite first in his original 1897 paper. demarquayi and F. that the second name given by Manson. perstans (which he had described the previous year) at the autopsy of patient who had had microfilaria perstans and microfilaria ozzardi in his peripheral blood. Low reported that he had compared microfilaria demarquayi from St. especially C. demarquayi in the mesentery of an infected patient in St Lucia 121. He described the parasites. that the filaria Demarquayii of St. He described the morphology of the worms. Treatment is unnecessary. PERSTANS The blunt-tailed microfilaria of M.f. were implicated in transmission in parts of South America332. in any case. Diagnosis depends upo n recovery of microfilaria from the blood. These events and the naming by Manson of the parasite first Filaria sanguinis hominis mino r (because of the smaller size of the microfilaria when c. none in available. as it does not implicate important structures. in skin samples 184. 87 In 1898. Simulium species. ozzardi.335. Very probably it may be the parental form of filaria perstans. with perhaps the exception of setting up some slight local inflammation on its death. Th e finding by Manson in 1897 of a similar microfilaria in blood sent to him from Central America 202 is recorded in the section on M. In the following year.190 This latter concept has since stood the test of time. Manson had written in 1897 that although he did not known what the y were. he had no doubt that the pa rasite had some pathological consequences 202. then its designation as Filaria sanguinis hominis perstans (later F. and since all the female worms had blunt-tailed larvae. it cannot do much harm. One of them soon died. Manson described two Congoles e patients with sleeping sickness who were also infected with F. it seemed likely that they were the parental form o f microfilaria perstans. Daniels wrote: Although this is undoubtedly a new species of filaria I do not propose at present to give it a name. seeing that it may turn out to be the parental form of one of the already known and named species of nematode embryos described by Manson. As the habitat of the parent is in the loose connective tissue of the peritoneum. I n December 1897. This observation stimulated C W Daniels in British Guiana to search for the parent worm. perstans 203. Daniels declared that there was as yet n o evidence of a pathological role for these worms as most infected person s seemed to be in good health. or less frequently. perstans was found by Mackenzie an d Manson in 1890 in the same patient (who later died from sleeping sickness) in whom they discovered what turned out to be microfilaria loa. perstans to meet the needs of binomial nomenclature) because it had no periodicity in contrast to the nocturnal periodicity of microfilaria bancrofti and the diurnal periodicity of microfilaria loa 201 have been described in chapter 23. This view was echoed by Low in 1902: The presence of the parental and embryonic forms of filaria Demarquayii seems to give rise to no pathological effects or clinical symptoms. however. he was rewarded with success in finding male and femal e worms in the mesentery and in subpericardial fat in two individuals who had had both microfilaria perstans and microfilaria ozzardi in their blood during life. and Mr O'Neill of the Charing Cross Hospital found a mature filaria in the connective tissu e .736 A History of Human Helminthology blackflies. microfilaria loa)200. even when the worms were numerous 88. M. austeni 146. In 1935. Henry and Langeron 276 transferred it to the genus Acanthocheilonema which had been raised in 1870 b y Cobbold75. Faust 109 described the genus Tetrapetalonema and Yeh354 then Chabaud and Bain in 1976 55 placed it in this genus. This possibility was banished. but then transiently entertained the idea that it might be the cause of sleeping sickness200. Fülleborn succeeded in achieving some development of microfilariae in Anopheles maculipennis 118. perstans in Culicoides grahami 103. Manson comp ared this with the nematode from the Americas described by Daniels and determined that they were the one and the same. so it became known as Dipetalonema perstans. he provided a more formal and detaile d description of the events. thus becoming Acanthocheilonema perstans . In 1912. Low wrote: Filaria perstans. grahami was a possible but poor vector when compared with C. This brought a fulsome response from Low who may have thought that Bastian himself was bananas: "filari a perstans has nothing to do with the genus Tylenchus nor do bananas play any part in the distribution or spread of this filaria" 192. Thereafter. but in 1927 Dyce Sharp in a preliminary note announced the development of F.Miscellaneous Nematode Infections 737 behind the abdominal aorta. However. the worm thus being described as Tetrapetalonema perstans . however. Yorke and Maplestone357 considered that Acanthocheilonema was a synonym of Dipetalonema erected by Diesing in 1861 94. gives rise to no pathological symptoms. perstans 14. changes in the nomenclature of this parasite became rather like a game of musical chairs. like filaria Demarquayii. when th e different geographical distributions of the two conditions were established and the trypanosomal aetiology of the illness was ascertained. for in 1982. perstans was really a member of the genus Tylenchus which contained nematode parasites of plants. The unorthodox Charlton Bastian postulated that F. In 1903. An interesting but odd exchange over the transmission of infection took place at the beginning of the present century. In 1952. Sergent and Gouillon reported unsuccessful attempts to infect Culex pipiens 301. Railliet. Bastian returned to the fray adducing various arguments 21 which were once more refuted by Low 193. In the following year. the position of the worms in the connective tissues of the mesentery apparently causing . Initially. In 1908. perstans infection.201. austeni 104. Hopkins and Nicholas showed that C. This opinion was supported soon afterwards by Low 191. Manson ascribed no pathological consequences to M. it is therefore known currently as Mansonella perstans. Orihel and Eberhard redefined the genus Mansonella and transferred this worm into that genus 242. thus proving that Daniels had indeed discovered the adult form of F. In 1921. however. Not to be outdone. with the product ion of infective larvae eight days after experimental infection of C. Analogy with other filarial parasit es suggested that this worm was probably transmitted by insect intermediate hosts but a number of years were to pas s before this was proven. and suggested tha t infection was acquired by eating bananas 20. This fashion was evanescent . STREPTOCERCA In 1922. The same parasites were found later by Dyce Sharp in 1927 in the British Cameroons (Cameroon) 102 then by other observers in West and Central Africa. then they found the adult male in 1977 211. respectively. Sections of the skin showed that they were lying in the dermis and were surrounded by a slight degree of cellular infiltration .323. Meanwhile. In 1976. The diagnosis is made by finding th e microfilariae in the blood.738 no harm. most commentators have upheld this view. crook-shape d posterior end. INFECTION WITH MENINGONEMA PERUZZII In 1973 Orihel and Esslinger described Meningonema peruzzii which had been collected from three monkeys (Cercopithecus talaporn )243.191 A History of Human Helminthology Although there have been occasional claims to the contrary 71. M. Like M. naming it Dipetalonema streptocerca. The adult female worm was first di scovered in human tissue by Meyers and his colleagues in 1972 209.227. Faust 110 transferred it to the genus Acanthocheilonema of Cobbold 75 thus naming the worm Acanthocheilonema streptocerca. Orihel and Eberhard 242 in 1982 considered that Tetrapetalonema was synonymous with Mansonella and renamed the parasite Mansonella streptocerca. milnei was also a vector. The sam e . Chardome and Peel showed in 1949 that this parasite was transmitted by Culicoides grahami 60. perstans. The generic name is derived from a combination of the Greek words µ (MENINX) and µ (NEMA) meaning "membrane" and "thread". Diethylcarbamazine has little action on the worm 139 but mebendazole may be active 338. this parasite has had a complex nomenclatural history. Peel and Chardome 251 in 1946 had reported the discovery of two female worms and a fragment of a mal e worm in a chimpanzee (Pan paniscus) in the Belgian Congo (Zaire) and had placed the parasite in the genus Dipetalonema of Diesing94. then Duke100 proved that C. The infection may be asympyomatic but some dark skinned persons presen t with itching and hypopigmented macules. and a blunt tail. JW Macfie and TF Corson on the Gold Coast (Ghana) found microfilariae in the skin of 22 out of 50 healthy adults which could be distinguished from those of Onchocerca volvulus by having a slender body. Chabaud and Bain 55 transferred it to the genus Tetrapetalonema of Faust109 to become Tetrapetalonema streptocerca . In 1949. Meyers and colleagues reported that diethylcarbamazine kills microfilariae in the tissues and produces degenerative changes in adult worms 210. MacFie and Corson placed these worms in the genus Agamofilaria of Stiles320 and named them Agamofilaria streptocerca 195.219. Finally. The generic name is derived from a combination of the Greek words µ (META) and (STRONGYLOS) meaning "with" and "round". clear region on the posterior half of the body106. INFECTION WITH METASTRONGYLUS ELONGATUS In 1845. He named this parasit e microfilaria semiclarum because it had a long. respectively . INFECTION WITH MICROFILARIA SPECIES (Adult worm undescribed) M. Dujardin described Strongylus elongatus. M. Orihel240 then suggested that these worms were the true cause of the meningoencephaliti s attributed by Dukes and his colleagues to Dipetalonema (= Mansonella) perstans 101. the first being described by Dujardin in the respiratory tract of a six year ol d boy99.Miscellaneous Nematode Infections 739 worms had been reported by Peruzzi in 1928 in Uganda 253. Chatin in 1888 reported infection in the gastrointestinal tract of a pork vendor 61. SEMICLARUM In 1974. BOLIVARENSIS This unsheathed microfilaria was found i n the blood of American Indians living in a remote part of Venezuela and reported by Godoy and colleagues in 1980 125. Microfilaria indistinguishable from this parasite were seen in skin biopsies of people in Gabon b y Richard-Lenoble and colleagues in 1982 281. Railliet and Henry 273 transferred this worm to the genus Metastrongylus which had been erected by M olin in 1861 216. a parasite of the respiratory tract of pigs99. INFECTION WITH MICRONEMA DELETRIX This species was described by Anderson and Bemrick in 1965 from thousands of worms found in bilateral tu mours in the nares of a horse in the United States of America 12. M. MICROS) and µ (NEMA) meaning "small" and . reservoir host. and life cycle are unknown. RODHAINI This infection was first described from the chimpanzees Pan paniscus and Pan satyrus by Peel and Chardome in Zaire in 1946 251. In 1911. The adult worms. The generic name is derived from a combination of the Gree k words µ (MIKROS. Infections in humans are very rare. Fain reported the finding of a dis tinctive unsheathed microfilaria in the blood of 52 inhabitants in three villages in Zaire. stephanosum described by Stossich in 1905 322. INFECTION WITH NECATOR SUILLIS This hookworm parasite of pigs was designated Necator suillis by Ackert and Payne in 19231. Only three adult worms were recovered afte r treatment with oil of chenopodium 44. The generi c name is derived from a combination of the Greek words (OESOPHAGOS) and µ (STOMA) meaning "gullet" and "mouth" . bifurcum by Creplin in 79 1849 . apiostomum infection in man after the parasite was collected by Foy in Nigeria 178. More recently. . apiostomum by Willach in 1891 . respectively. O. INFECTION WITH OESOPHAGOSTOMUM SPECIES A number of species of the genus Oesophagostomum. Operative intervention may be necessary to effect the diagnosis or to reliev e intestinal obstruction. usually 1-2 cm in diameter. are parasites of subhuman primates. Eggs were first seen 54 days after the first application to his skin and continued to be passed over the next four months. raised by Molin in 1861216. suillis recovered from pigs at an abbatoir in Trinidad. Included amongst those which may occa sionally infect humans are O. the first being reported by Hoogstraten and Young in 1975. then Leiper reported O. The most common presentation was as a mass in the ileocaecal re gion although nodes or abscesses. a 5 year old boy in Canada died from meningoencephalitis caused by the worm after he passed through a manure spreader and sustained multipl e lacerations 145. Buckley in 1932 infected himself on 11 separate occasion s with infective larvae (about 80 worms each time) prepared from eggs obtained from N. No anthelmintics have yet been shown to be effective. especially in the caecum an d colon. brumpti by Raillet and Henry in 1905 268 and O. Anthony an d McAdam reviewed 34 cases seen in Uganda. O. O. The first human infection was found in a person from the Omo River in East Africa 268. swine and sheep. aculateum by von Linstow in 348 1879 185. may be seen in other parts of the small and large bowel 15. deletrix-like worm have been recorded. some of these may be synonyms of each other. bifurcum described by Creplin in 1849 79. respectively. O. These parasites are often called "nodular worms" since the y produce large nodules in the wall of intestine. Three fatal cases with this parasite or a M.740 A History of Human Helminthology "thread". horses. described in 1866 by Schneider 299. Leiper also described a worm that had been removed from the stomach of a person in Uganda and named it P. sheep or goats169. Another patient has been described recently in whom worms that were probably Physaloptera caused gangrene of the distal small bowel 235. Two years later. INFECTION WITH PHYSALOPTERA CAUCASICA This worm was found in the ileum of a patient in the Caucasus and name d Physaloptera caucasica by von Linstow in 1902 186. but they may also be found in the liver. He later suggested that monkeys may be the reservoir of infection180. circumcincta in the stools of a patient after administration of anthelmintics 159 then reported the discovery of a single O. von Ostertag described a parasite recovered from cattle which h e named Strongylus convolutus 244. The life cycle of this worm is unknown and the treatment of the infection is uncertain. 2-10 cms long. ostertagi in the small intestine of a man at autopsy 160. In 1894.Miscellaneous Nematode Infections INFECTION WITH OSTERTAGIA SPECIES 741 In 1890. respectively. live with their head embedded in the mucosa of the alimentary tract anywhere between th e oesophagus and the ileum. . cattle and sheep. INFECTION WITH PELODERA SPECIES Pelodera strongyloides. mordens 176. Ransom erected the genu s Ostertagia and transferred these worms into it. Stadelmann described a similar parasite in sheep which he named Strongylus circumcincta 315. and the skin of dogs. The worms. is a parasite of the orbit of wild rodents. The generic name is derived from a combination of the Greek words (PHYSALIS) and (PTEROO) meaning "bubble" and "wing". In 1907 . Kasimov recorded finding two male sp ecimens of O. Lapage noted in a comment on these papers that it was possible that these worms might have been ingested in uncooked or partly cooked abomasum of cattle. The infection is rare in humans although Vandepitte and colleagues in 1964 reported finding five cases in Zaire in one year. the parasites thus becomin g known as Ostertagia ostertagi and Ostertagia circumcincta 277. In 1941. These patients complained of vomiting an d epigastric pain and eggs were found in their faeces336. In 1907. Stiles renamed it Strongylus ostertagi 317. Huma n infection has been reported once when it was found infecting the skin of an 11 year old Polish girl 250. In 1959. In a subsequent survey in . deminutus-like eggs from the faeces of a medical missionary who had spent 25 years in Africa. respectively. Rhabditis species have also been found in urine 113 and in skin 236. Biocca reported the case of an infection of a baby who had been born on e month prematurely and had developed intestinal obstruction and peritonitis as a consequence of worms embedded in her terminal ileum 38. and indicates the presence of three complex teeth in the buccal cavity. Rhabditis species found in faeces have usually been ingested in contaminated food or water and have passed through th e alimentary tract or have contaminated faecal droppings deposited on the soil. It is believed that the mother must have ingested an infected beetle while pregnant. The generic name Ternidens is derived from a combination of the Latin words "ter" and "dens" meanin g "thrice" and "tooth". INFECTION WITH SPIROCERCA LUPI This parasite of wolves and dogs was named Strongylus lupi by Rudolphi 291 in 1809 then transferred to the genus Spirocerca of Raillet and Henry 273. an d produced an experimental infection in a vo lunteer. The worms are normall y parasites of rodents and bats but an adult female worm has been seen in New York in a human appendix 161. the worms wer e expelled spontaneously in 2-3 months 163. In 1929 Sandground recovered T.742 A History of Human Helminthology INFECTION WITH RHABDITIS SPECIES The genus Rhabditis was erected in 1845 by Dujardin 99 to house a number of species of free-living nematodes which live typically in decaying organic matter but which may occasionally be found temporarily on damaged human tissue or in the lumen of various organs. hominis in 17 students in Japan and noted that there were no ill-effects. INFECTION WITH TERNIDENS DEMINUTUS This parasite of the large intestine of several simian species was described as Triodontophorus deminutus by Raillet and Henry 267 in 1905 then renamed Ternidens deminutus by them in 1909 270. INFECTION WITH RICTULARIA SPECIES This genus was erected by von Frölich in 1802 117. although he failed to recover adult worms after carbon tetrachloride treatment 294. Infection of a woman with this parasite was reported by Leiper in 1908 175. cultured larvae. Kobayashi reported finding a Rhabditis which he called R. erected by Myers 230 in 1959. was described b y Railliet and Henry271 in 1910. More recently. The worm usually causes littl e conjunctivitis but often stimulates marked tear production.Miscellaneous Nematode Infections 743 Southern Rhodesia (Zimbabwe). CALLIPAEDA This worm. In 1917. The infections were thought t o have been acquired by eating raw fish. however. Fannia) as intermediate hosts. 30 cases have now been reported from Japan 155. The generic name is derived from the Gree k word (THELAZO) meaning "to suck". The genus was named after the ship (itself named "Terra Nova" meaning "new land") which took the party to th e Antarctic. thiab endazole128 and pyrantel embonate 129 have been shown to be effective. The first human infections were reported in Japan in 1972 by Suzuki and his colleagues who described 5 patients in whom a larva was seen penetrating the gastric mucosa 325. considered that the parasite was almost certainly T. an opinion which was shared by Faust 107. as did Goldsmid many year s later 127. The worm may be removed with forceps after anaesthesia of the eye. he found that in some regions more than 50% of the population were infected 295. A number of similar cases have bee n reported since. which was found in a dog. callipaeda 181. the latter describing the male worm for the first time and showing that rabbits were a host. Sandground used carbon tetrachloride and tetrachlorethylene i n treatment. Koyama and colleagues then described the morphology of the larvae removed from these patients 166. According to Kagei and colleagues. are indistinguishable from those of Terranova. INFECTION WITH TERRANOVA SPECIES This genus was erected by Leiper and Atkinso n in 1914 to house certain worms collected by Atkinson during the ill-fated British Antarctic Expedition o f 1910-1913 led by Captain Scott 182. INFECTION WITH THELAZIA T. The life cycle is probably similar to that of Anisakis. . Some of these may b e due to infection with Phocanema species since the larvae of this genus. Leiper. 5-17 mm in length. The life cycle is uncertain but other species of Thelazia use flies (Musca. He attempted to transfer infection to more humans and to subhuman primates but failed. Stuckey 324 and 147 Houghton in China described infections of the human eye with a worm they identified as Filaria palpebralis. Movement over the corneal surface can cause corneal opacities. the illness was ascribed to infection with this parasite 252. larvae migrate into the tissues. however. but they are questionable. Biopsy revealed focal necrotic lesions with numerou s polymorphonuclear and eosinophilic granulocytes and giant cells. transient diarrhoea . Several cases have been reported since. It was first described by Kofoid and Williams 164 in 1935 after two worms. In dogs. infection is usually acquired across the placenta or via the mother's milk. CARA) meaning "bow" and "head". 10-13 mm long. In view of the fact that he "improved remarkably" after he vomited a single male A. were removed from the eye of a doctor wh o complained of an irritation in his eye. then in 1950 Mercer and colleagues found nematode larvae which they indentified as A. in 1950. which had been erected by Stiles in 1905 319. such lar vae have been shown to remain alive for at least nine years 24. weight loss. called it Belascaris mystax 174. although infective egg s in soil or larvae in paratenic hosts may be ingested 314. fail to mature and become encapsulated. he remembered that some flying insect had hit his eye ten days previously. as did Behrer in the following year 31. The name Toxocara is derived from a combination of the Greek words (TOXON) and (KARA. canis larvae in humans. hepatomegaly and marked eosinophilia. In 1907. lumbricoides in lesions in the liver of a patient with a similar condition 208. lumbricoides. Helenor Wilder of the United States Armed Force s . A similar case was described by Zuelzer and Apt two years later 360. probably being in reality immature Ascaris lumbricoides 39. In 1947. When paratenic hosts are infected. Leiper erected the genus Belascaris and. Meanwhile.744 T.350. Because the vomiting continued and abdominal distension developed. In 1916. respectively. TOXOCARIASIS TOXOCARA CANIS This ascarid parasite of dogs was described by Werner in 1782 as Ascaris canis 343. and named it Toxocara canis 154. Johnston transferred the worm to the genus Toxocara. vomiting. In monkeys. CALIFORNIENSIS A History of Human Helminthology This species has been recovered from a number of animal and bird hosts i n California. gray-white lesions scattered over the smooth surface of all lobes"252. he was subjected to laparotomy and the liver was found "to have small. This fate also befalls T. Josephine Perlingiero and Paul György of the Philadelphia General Hospital reported the case of a two year old black boy admitted to hospital in 1944 with fever. There are rare records of the infection in humans by the adult form of this parasite. holding that Ascaris canis was synonymous with Fusaria mystax of the cat described by Zeder359. cough. in one of whom a larva was seen in a liver biopsy. over 1900 cases of toxocariasis had been reported from many parts of the world and most of these have been due to T. In 1956. it was pos sible to reconstruct almost the whole of the worm and it was concluded that it "resembled the infective stage o f Toxocara canis or T. The diagnosis may be established by finding larvae in biopsy specimens but this is often difficult. Histological examination. that the fact that the larvae in these cases had been identified as being probably those of hookworms did not rule out other nematodes such as Strongyloides and Ascaris as possible causes of this endophthalmitis. they coined the term "visceral larva migrans" to distinguish it from cutaneous larva migrans caused by larvae of Ancylostoma braziliense and other parasites in the skin. nematode larvae were found in serial sections. Smith and Beaver produced the disease experimentally in humans. Toxocara ova were found in soil samples of 45% of dooryards in New Orl eans140 and in 24% of public parks in Britain 41. Irvine and Irvine reported finding T. Most of the childre n came from the southeastern USA and Wilder concluded: The findings of intraocular larvae by serial sectioning and the identification of the specific pathologic reaction that they evoke has led to the conclusion that nematodes play an important and hitherto unrecognized role in blindness in children 347 In 1952. canis and T. however . By 1981.234. anaemia and eosinophilia. canis to two mentally defective children aged two and three years. This result was confirmed in a human volunteer by Chaudhuri and Saha in 1959 62. Carrera. from whom an eye had been enucleated because of a suspected diagnosis o f retinoblastoma. A precipitin test was described in 1956 by Heiner and Kevy141 and a skin test a few years later 351. Mice were thereupon infected with T. Nichols re-examined five of Wilder's cases and identified the larvae in the eyes as those of Toxocara 233. cati eggs and worms similar to that found in the human case wer e demonstrated subsequently in histological sections 29. Matthes and Buchwalder considered a microprecip itation test using live larvae as the most useful . Beaver and his colleagues. Immunodiagnostic assays are therefore valuable. In the following year.Miscellaneous Nematode Infections 745 Institute of Pathology had described an ocular disease which she called nematode ophthalmitis. Infection is therefore common in children who ingest soil (pica). both developed eosinophilia and some degree o f hepatomegaly311. They administered orally 200 embryonated eggs of T. cati 124. Dent and Lafferty. She discussed a large series of cases. then in 1959. cati" 29. By utilizing serial sections. and in 24 of 46 such specimens. revealed eosinophili c granulomas. the specimens are third stage hookworm larvae" 66. however. Consequently. A number of the m were examined by BG Chitwood who wrote: "So far as can be determined on the basi s of the material at hand. Infection in humans is usually acquired by ingestion of eggs in the soil . "by means of an experiment which cannot be commended" 349. respectively. canis but a few have been caused by T. mostly of children . Wilder remarked sagaciously. in New Orleans described three patients with hepatomegaly. More recently. canis larvae in the eye of a child in California 150. Snyder. Although infection could be established percutaneously. In contrast to T. Railliet and Henry in 1911 reverted to the specific description of Schrank. Koino reported that T.(TRICHO-)] and (STRONGYLOS) meaning "hair" or "thread" and "round". calling it Belascaris mystax 174. In 1911 Ranso m transferred S. In 1927 Brumpt transferred it to the genus Toxocara of Stiles319. T. According to von Reyn and colleagues. Railliet described S. Some larvae complete their development to for m adult worms in the gut of young cats but most larvae migrate to the muscles in older cats 313. Complete development in humans is rare. cati may cause visceral larva migrans. Zeder in 1800 named it Fusaria mystax359 . axei 269. skrjabini 157 and T. T. The generic name is derived from a combination of the Greek words (THRIX) [combining form . respectively. but many of these may be spurious o r follow the ingestion by a child of a young adult worm. transferred S. All of the above species are now known to infect humans. There have been scattered reports that th e infection responds to treatment with thiabendazole 232. instabilis and S. More commonly. canis. CATI This ascarid parasite of cats was described as Ascaris cati by Schrank in 1788300. Looss erected the genus Trichostrongylus. T. and described a new species. he believed that oral infection was th e usual and more efficient mode of infection 165. probulurus 264. Other species described were T. vitrinus 188. The first such patient was possibly reported by Pickells in Ireland in 1824254 then more probably by Bellingham O'Brien32 in the same country a few years later then by Cobbold in England in 1863 74. Monnig218 then Hasegawa137 . Belascaris. orientalis 153. T. there have been 20 reports of infection in humans 280. but this has not always been the experience 17. Cats acquire the infection by ingesting embryo nated eggs or larvae in paratenic hosts. TRICHOSTRONGYLIASIS In 1892. In 1905. In 1925. it thus being designated Toxocara cati 43. then Rudolphi renamed it Ascaris mystax 288 and Leiper in 1907 used it as the type species of his new genus. colubriformis into the genus Trichostrongylus 278. orientalis infections in mice seemed t o follow the same route through the lungs as do hookworms. T. brevis 245. probulurus into it. Photocoagulation of the eye lesions is sometimes possible148. naming it Belascaris cati 274. transplacental transmission does not occur but t ransmammary transmission is common. Similar contradictory results have followed treatmen t with diethylcarbamazine 312. Giles in India recov ered a worm which he named Strongylus colubriformis from nodules in the intestine of a sheep 123.746 A History of Human Helminthology immunodiagnostic procedure 207. instabilis 263 then in 1896 he also described S. In the following year. 1885 4. the larvae migrated into the mucosa and matured in about three to four weeks. These various surveys revealed that in the vast majority of patients. Annali di Ottalmologia. Studies on the occurrence. Milano 14: 135-148. colubriformis. however. Su di un nem atode dell'occhio umano. Stewart showed that 70% of the population in one part of Iran was infected 316. Philippine Journal of Science 61: 221-225. 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The etiology of visceral larva migrans. Cerebral filariasis in five monkeys infected with trypanosoma l meningoencephalitis. PERLINGIERO JG. CHARDOME M. 1954 247. American Journal of Tropical Medicine and Hygiene 17: 548-550. Acta Medica et Biologica 9: 273-278. The etiology of visceral larva migrans. et sp. (On the life history of Hepaticola hepatica . Morphology and relationship of Dirofilaria tenuis and Dirofilaria conjunctivae. II.) Taiwan No Ikai 3: 589-592. PEEL E. Eosinophilia and hepatomegaly due to Capillaria hepatica. British Journal of Dermatology 98: 107-112. Southeast Asian Journal of Tropical Medicine and Public Health 4: 131-134. RAILLIET A. Sur une filaire péritonéale des porcins. Encore un nouveau sclérostomien ( Oesophagostomu m brumpti nov. nouveau sclérostomie n parasite de l'homme. HENRY AC. RAILLIET A. HENRY AC. RAILLIET A. PUNYAGUPTA S. Feeding experiments of cats with Gnathostoma spinigerum larvae obtained from the second intermediate host. (Editor). In. Syngame laryngien du boeuf. Bulletin du Muséum d'Histoire Naturelle. 1911 275. Recent knowledge on clinical gnathostomiasis. 1909 270. RAILLIET A. PROMMAS C. RAILLIET A. HENRY AC. from her stomach. POLTERA AA. HENRY AC. Journal of Parasitology 22: 180-186. 1910 272. Indian Medical Gazette 23: 115-116. Bulletins de l a Société de Pathologie Exotique et de ses Filiales 4: 386-389. DAENGSVANG S. nématode s parasites de l'oeil. American Journal of Tropical Medicine an d Hygiene 11: 759-761. HENRY AC. pp 712. Transactions of the Kings and Queens College of Physicians of Ireland 4: 189-214. RAILLIET A. a number of insects in different stages of their existence. Sur la classification des Strongylidae. HENRY AC. Précis de parasitologie humaine. 1909 271. Comptes Rendus Hebdomadaires de s Séances et Mémoires de la Société de Biologie 66: 85-88. 1893 264. PRADATSUNDARASAR A. Comptes Rendus Hebdomadaires des Séances et Mémoires de l a Société de Biologie 68: 783-785. pp 736 . HENRY AC. 1824 255. Compte s Rendus Hebdomadaires des Séances et Mémoires de la Société de Biologie 70: 12-15. 441-446. 1973 256. The first case of intestinal capillariasis in Thailand. CHINTANAWONGS C . Paris 11: 269-272. 1937 260. Sur la classifica tion des Strongylidae. 1962 261. Comptes Rendus Hebdomadaires des Séances et Mémoires de la Société de Biologie 58: 643-645. 1936 259. PECHARANOND K. Recherches sur les ascarides des carnivores. Comptes Rendus Hebdomadaires de s Séances et Mémoires de la Société de Biologie 51: 174-176. Helminthes du porc recueillis par M Bauche en Annam . PRADATSUNDARASAR A. M Neveu-Lemaire. 1973 257. PROMMAS C. et la cachexie africaine. second edition. DAENGSVANG S. Huma n angiostrongyliasis of the eye in Bangkok. Further report of a study on the life-cycle o f Gnathostoma spinigerum . Sur les variations morphologiques des strongyles de l'appareil digestif. Comptes Rendus Hebdomadaires de s Séances et Mémoires de la Société de Biologie 66: 167-171. 1933 258. Metastrongylinae. 1967 262. 1885 263. PROMMAS C. pp 586. HENRY AC. Preliminar y report on the life-cycle of Gnathostoma spinigerum. Nouvelles observations sur les thélazies. HENRY AC. RAILLIET A.Miscellaneous Nematode Infections 759 254. J Lamarre. PROMMINDAROJ K. Comptes Rendus Hebdomadaires des Séances et Mémoires de la Société de Biologie 48: 540-542. Journal of th e Medical Association of Thailand 50: 686-695. RAILLIET A. Quelques nématodes parasites des reptiles. Case of a young woman who has discharged and continues to discharge. Transactions of th e Royal Society of Tropical Medicine and Hygiene 67: 819-829. LEELAWONGS N. Paris. 1905 269. Éléments de zoologie médicale et agricole. 1908 267. The histopathology of ocular loiasis in Uganda. DAENGSVANG S. 1905 268. RAILLIET A. Bulletins de la Société de Pathologie Exotique et de ses Filiales 4: 693-699. Traité de zoologie médicale et agricole. II. I. Paris. 1911 273. Maladies parasitaires dues à de s végétaux et à des animaux. 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Foyer de filariose humaine a u Gabon à microfilaire dermique indifférenciable de microfilaria rodhaini. ROSEN L. sive experimenta circa varias res naturales . SANDGROUND JH. RICHARD-LENOBLE D. 1986 287. In. Eosinfiele flegmone van de dunne darme . speciatim illas quae ex indiis afferuntur etc. Owen. sive vermium intestinalium historia naturalis. Ternidens deminutus (Railliet and Henry) as a parasite of man in Southern Rhodesia. pp 312. CHAPPELL R. Notes on parasitic nematodes. Tropical Medicine and Hygiene News 35: 114-117. T Haak et S Luchtmans. OWEN R. WIELINGA WJ. thre e volumes. BEAVER PC. KOMBILA M. LOPES MB. RUDOLPHI CA Entozoorum. veroorzakt door een worm. In Russian 293. Journal of Pediatrics 93: 247-249. and observations on life histories. 1912 277. LAQUEUR GL. ROSEMBERG S. BAIN O. SANDGROUND JH. (Editor). three volumes. United States Department o f Agriculture. 1907 278. quae in corporibus animalium vivorum reperiuntur observationes. 1922 284. RODENBURG W. ROSEN L. 1802 290 RUDOLPHI CA. Bureau of Animal Industry. RANSOM BH. pp 1370. HENRY AC. Eosinophilic meningoencephalitis caused by a metastrongylid lungworm of the rat . Deutsche medizinische Wochenschrift 92: 2230-2233. (Neue Fälle der Hepaticolosis beim Menschen. 1949 317. SERGENT E. Die Heterocheilidiasis. Monographie der Nematoden. Oekologie und Geographie der Tiere. Parasitology 48: 185-198. Englis h translation. SKRJABIN KI. Jerusalem. Sitzungsberichte der Gesellschaft Naturforschender Freunde zu Berlin. SHIKHOVALOVA NP. Pediatrics 28: 85-91. Zoologische Jahrbücher.) "Russian Journal of Tropical Medicine" 7: 449-450 . VI. Capillaria hepatica infestation in a child. SILVERMAN NH. SMITH JW. 1975 306. 513-515 . SINGSON CN. 1957. POJDAPOLSKAYA WP. SKRJABION KI. SKRJABIN KI. STILES CW. Moscow. British Journal of Ophthalmology 29 : 618-626. 1961 313. Experimental studie s on the migration of Anisakis sp. Journal of the American Medical Association 123: 694-695. SEN K. SMITH DC. Berlin 1866 300. On the potential longevity of various helminths with a record of a species of Trichostrongylus in man. BANZON TC. SPRENT JF. 1958 315. SANDGROUND JH. 1956 314. pp 116. 1953 312. pp 420-423.) In Russian. 1945 303. GOUILLON P. SCHNEIDER AF. Human infestation with Trichostrongylus in South Persia. 1931 296. 1921 302. 1894 316. A word in regard to the Filaridae found in the body cavity of horses and cattle. Israel Progam for Scientific Translation. The life history and development of Toxocara cati (Schrank) 1788) in the domestic cat. Pediatrics 12: 491-496. SCHAUM E. 1967 299. Verzeichnisse der b isher hinlängich bekannten Eingeweidewürmer nebst einer Abhandlung über ihre Anverwandtschaften. 1930. SCHOULMANN ES. 1936 297. Archives des Instituts Pasteur de l'Afrique du Nord 1: 85. Journal of the American Medical Association 91: 938-943. In Russian. the treatment of creeping eruption with sodium antimony biscatecho l (Fuadin). braziliense). (Premier cas de Dirofilaria repens chez l'homme. Visceral larva migran s . MÜLLER W. Parasitology 46: 54-78. LEVIN SE. 1977 298. A discussion of certain questions of nomenclature as applied to parasites. Experimental creeping eruption from a cat and dog hookworm ( A. Observations on the development of Toxoocara canis (Werner 1782) in the dog. GHOSE N. . Academy of Sciences of USSR. WOOTTEN R. A precipitin test for the diagnosis of human abdomina l angiostrongyliasis. pp 416-419. Clupea harengus L. SCHRANK FP. American Journal of Tropical Medicine and Hygiene 26: 1156-1158. with French summary 308. 1928 304. SNYDER CH. 1892 318. STADELMAN H. SPRENT JF. Persistence and dis tribution of Toxocara larvae in the tissues of children and mice. Journal of Comparative Medicine and Veterinary Archives 13: 143-147. KATZ JS. CROSS JH.Miscellaneous Nematode Infections 761 Annals of Tropical Medicine and Parasitology 25: 147-184. Abteilun g für Systematik. ALGANSES AJ. American Journal of Tropical Medicine and Hygiene 24: 932-934.) Tropickeskaya Meditsina i Veterinariya. Trichocephalidae and Capillariidae of animals and man and diseases caused by them . larvae (Nematoda: Ascaridida) into the flesh of herring. In Russian. Eine Infektion des Menschen mi t Larven von Fisch-Ascariden. pp 357. Moscow 2: 9. ORLOV IV. 1943 310. BEAVER PC. 1788 301. SCHICHOBALOWA NP. München.ten years' experience. South African Medical Journal 47: 219-221. Ocular gnathostomiasis. STILES CW. 1975 311. Essais d'inocul ation à un singe d'une filariose humaine par des piqûres de Culex pipiens. pp 142-146. 1929. 1970 309. Ueber Strongylus circumcinctus . 1973 305. British Medical Journal ii: 737-739. International Journal for Parasitology 5: 133-136. (Essentials of nematodology. Mebendazole in the treatment of intestinal capillariasis. Journal of Parasitology 22: 464-470. SAUERBREY M. STEWART IS. SMITH MH. with German summary 307. SHELMIRE B. einem neuen Parasiten aus de m Labmagen des Schafes. A cutaneous nematode infection in monkeys. the final hosts of the herringworm Anisakis marina. CW St iles and A Hassall. 1965 322. and the ova and larvae of a nematode worm in th e urine. 1901 319. TADA I. Archives of Dermatology 91: 427-429. 1800. 1966 331. Journal of Parasitology 2 : 119-125. 1962 324. Journal of Experimental Medicine 35: 599-620. TIDWELL M. 1904 323. MICHAUX JL.) Hifu-Ka Oyobi Hinyoôki-Ka Zasshi pp 827-834. Zeder. of man. UNDIANO C. 891-910. 1927 338. STOSSICH M. MILLER CP. Annuario del Museo Zoologico della Real e Universita di Napoli. 1980 333. A nematode parasitic to herring. Terranova (Nematoda: Anisakidae) infection in man. SUZUKI H. from the ankle of a negress. Annales de la Société Belge de Médecin e Tropicale 44: 1067-1076. 1924 327. 1905 320. Abhandlungen aus dem Gebiet der Auslandkunde. Contribui ções par o conhecimento da fauna helmintolojica brasileira. 1873 . TAMURA H. Lancet i: 336-338. YOKOGAWA M. STONE OJ. United States Public Health and Marine Hospital Service. V. KOYAMA T . Journal of Tropical Medicine and Hygiene 65: 230-232. van THIEL PH. Importancia y actualización del nuevo concepta da la patogenicidad de la mansoneliasis. Abstracted in Tropical Diseases Bulletin 18: 116-117. The successful treatment of Dipetalonema perstans filariasis with mebendazole. American Journal of Tropical Medicine and Hygiene 28: 988-990. STILES CW. Premières observation s congolaises de physaloptérose humaine. Medical Journal of Australia i: 405-407. KUMADA M. FAIN A. China Medical Journal 31: 24-25. Sobre as especies brasileiras do genero Capillaria. GATTI F. MULLINS JF. Annals of Tropical Medicine and Parasitology 76: 557-559. 1972 326. Sopra alcuni nematodi. WARD HB. SAKAGUCHI Y. Bulletin 34. sp. 1919. Dirofilaria in the abdominal cavity of a man i n Japan. In Japanese . Annales de Médecine 27: 414-425. and a list of roundworm genera with their original and type species. Hamburg Universität 26: 573-578. 1907 321. WAHLGREN M. 1: 1-4. Japanese Journal o f Parasitology 21: 252-256. causing acute abdominal syndromes in man. STOTT G. 1930 335. Colombia. 1917 325. I. 1921 330. 1960 332. pp 9-30. STILES CW. 1922 328. OHBAYASHI M. ETO K. MUÑOZ de HOYOS P. Bulletin (79). KARASAWA Y. SWEET WC. TROISIER J. Tropical and Geographical Medicine 12: 97-113 .. Gongylonema in the role of a human parasite. Memorias d o Instituto Oswaldo Cruz 7: 146-172. SWIFT HF. Hygiene La boratory. an apparently new roundworm parasite . ROSKAM TH. Bureau of Animal Industry. Clinical features of five cases of Terranova larva infection.762 A History of Human Helminthology Jena 15: 157-208. 1966 336. Revista de la Faculdad de Ciencias Médicas de la Universidad Nacional de Cordoba 24: 183-189. On a species of filaria fo und in the interior of the vascular system of a dog: relative to the filaria in the blood. OHNUMA H. Circumocular filariasis. 1964 337. 1915 334. American Journal of Tropical Medicine and Hygiene 29: 1209-1214. Development of Mansonella ozzardi in a black fly species of the Simulium sanguineum groups from eastern Vaupes. United States Department of Agriculture. VOGEL H. VANDEPITTE J. 1982 339. Tropical and Geographical Medicine 18: 310-328. Thiabendazole effectiveness in creeping eruption. The determination of generic types. Pathogenicity of Acanthocheilonema perstans . Ueber Mikrofilaria demarquayi und die Mikrofilaria aus Tucuman i n Argentinien. van THIEL PH. new series. The intestinal parasites of man in Australia and its dependencies as found by the Australian Hookworm Campaign. 1979 329. DESCHIENS R. KUIPERS FC. 1916 340. (On creeping disease. Agamofilaria georgiana n. L'hépatic oliase. pp 1-150. WELCH FH. BOOTS RH. TIDWELL MA. STUCKEY EJ. TRAVASSOS LP. Observations on the life cycle of Capillaria hepatica (Bancroft. 1970 350. Leipzig. Japanese Journal of Parasitology 28: 347-354. 1782 344. WELTY RF. British Medical Journal 283: 1124. 1929 347. WHITE GF. 1979 359.Miscellaneous Nematode Infections 763 341. 1873 342. 1963 343. Deraiophoronema freitastenti n. 1893) Cobb. YOKOGAWA S. On a filarial parasite. WOODRUFF AW. Disseminated visceral lesions associated with extrem e eosinophilia. Lancet i: 508. 1981 351. STRICKLAND GT. 1969 345. 1961 353. Chinese Journal of Microbiology 1: 148-150. 1893) with a description of the adult. Sclerostoma apiostomum nov. Urine chyleuses et hématochyleuses. YEH LS. part 2. 1950 348. A dermatitis caused by larvae of the Ancylostoma caninum . A new disease of man. WATTEN RH. American Journal of Tropical Medicine and Hygiene 12 : 888-891. ZUNE A. 1941 354. volume 1. 1926 358. DIZON JJ. MAPLESTONE RA. and a proposed reclassification of Dipetalonema and related genera. WILLACH P. Parasitology 47: 196-205. Clinicopathological studies on larval anisakiasis. British Medical Journal i: 1001-1005. Journal of the American Medical Association 90: 1701-1704. Not an i nfection with adult Toxocara canis. Vermium intestinalium praesertim taeniae humano. CHEN CY. Part 35. The causation of creeping eruption. Transactions of the American Academy o f Ophthalmology and Otorhinolaryngology 55: 99-109. 1928 346. APT L. Lancet i: 13-16. Erster Nachtrag zur Naturgeschichte der Eingeweidewürmer von J A E Goeze mit Zusätzen und Anmerkungen herausgegeben von Zeder. 1957 355. 1964 352. 1949 361.. WOODRUFF AW. 1891 . AKAO N. Archives of Dermatology and Syphilology 20: 191-200. Toxocariasis. Canadian Journal of Zoology 38: 167-182. with special r eference to the report of extra-gastrointestinal anisakiasis. WHITE GF. UYLANGCO C. WOODRUFF AW. The nematode parasi tes of vertebrates. SHAH A I. Lipsiae. 1800 360. WILDER HC. Infection with animal helminths. British Medical Journal ii: 663-669. ZEDER JG. pp 320. sp. Haematozoa. J&A Churchill. Tokyo 48: 507-512. WELCH FH. from the giant anteater Myrmecophaga tridactyla from British Guiana. London. sp. ZUELZER W. CHEN T. CROSS JH. Nematode ophthalmitis. 1891 349. Studies on the h elminth fauna of Japan. WHALEN GE. A human case of accidental parasitism of Diploscapter coronat a (Cobb. YAMAGUTI S. Ein neuer und gefährlicher Parasit der Affen. 1913. Japanese Journal of Parasitology 9: 409-439. CROSS JH. Siegfried Lebrech t Crusius. GUTMAN RA. Zoological Magazine. YOSHIMURA H. American Journal of Diseases of Children 78: 153-181. YII CY. Human angiostrongyliasi s involving the lungs. Dirofilariasis in man: report of a case from the state of Washington. YORKE W. 1968 356. THACKER CK. ONISHI Y. KONDO K. pp 82. FRESH JW. ROSENBERG EG. 1936 357. Mammalian nematodes II. LUDDEN TE. DOVE WE. brevis expositionis continuatio. BEAVER PC. Paris. WERNER PC. pp 28. pp 536. WRIGHT KA. SL Crusium. DOVE WE. Archiv für Wissenschaftliche und practische Tierheilkunde 17: 340-346. Intestinal capillariasis. Th e first arose in the faeces and of these there were said to be seven varieties . recent times. which were purely an d simply figments of the imagination. Thus. Finally. written around the first century AD. bein g thought to be hairy with spots and tails. was supposed to have fallen sick when a worm arose from his sputum and bit on the heel (cited in 24). It was not until autopsies of humans became commonplace that erroneous ideas of fantastic parasites wer e expunged. These arose from misguided interpretations of pathological changes such a s coagulated blood or necrotic tissue or secondary infestation of human tissues and excretions by non-parasitic organisms. pseudop arasites were also described. earworms. palate and ears. the sun-god of Egypt. alleged that there were three types of worms living in humans.some of these were undoubtedly real. Undoubtedly th e imaginary worms which were most widely held to exist were the toothworms. it was considered that they fed on the bone marrow and penetrated into the eyes. some of which were believed to feed on the roots of hairs which fell out as a consequence 93. umbilical worms and echo worms. nasal worms. have been dreamt up and claimed as the cause of disease in many societies until.Chapter 28 MISCELLANEA IMAGINARY WORMS AND PSEUDOPARASITES Imaginary parasites. usually worms. IMAGINARY PARASITES Imaginary parasites are well-described in the ancient literature. and including. A number of imaginary worms are detailed below. The Indian medical work. Six worms were thought to arise in the sputum. Ra. In addition to these imaginary parasites. They were all imaginary. corpse worms. Perhaps the earliest literary reference to 765 . but a number of others were frequently alleged such as eyeworms. Toothworms The belief that toothache and dental disease are caused by worms in or around the teeth goes back to ancient times. Worm s were frequently found in the viscera and tissues of animals killed for culinary purposes so it was a logical step to assume that similar worms must occur in humans and were likely to produce illness. seve n imaginary worms arose from the blood. th e Sushruta Samhita. In the present century. or apricots? Set me amid the teeth and let me dwell in the gums. What wilt thou give me to destroy?' 'I will give thee dried figs and apricots. Came unto Ea. such beliefs are still prevalen t among the poorly-educated in many parts of the world. associated worm s with dental disease in his De compositione medicamentorum 66.7) of the twentiet h dynasty (c. this formula was extolled in the . And of the gums chew their marrow.'"(cited in 95) Similarly.1200-1100 BC) in which an unhappy official at a desert outpost is recorded as complaining that a worm gnawed at this teeth 95. That I may destroy the blood of the teeth. An Assyrian tablet in the library o f Asur-bani-pal (c.' 'Forsooth. what are dried figs to me. 13. For example. written in the ninth century AD but largely a translation of Galen's De locis affectis (second century AD).766 A History of Human Helminthology such parasites is in an Egyptian papyrus (Anastasi IV. The earth made the rivers The rivers made the canals The canals made the marsh The marsh made the Worm. In the same manner in the Indian text. The worm came weeping unto Samas. The Assyrians recommended that it be p laced on a hollow tooth and Scribonius Largus described fumigation with the smoke of its burning seeds in order t o drive the worms out of decayed teeth. Claudius. a writer of the Ming dynasty (16th century AD) believed that worms recovered from patients with longstandin g toothache had black heads whereas those seen in acute cases had red heads 64. it was considered that dental caries arose when the teeth were eaten by worms 93. This concept that toothworms caused dental dise ase was accepted in Europe until the eighteenth century and was recorded in various leechbooks and books of herbal remedies 96. So shall I hold the latch of the door. 'What wilt thou give me for my food. Toothworms were also generally accepted in China.500 BC) mentions t oothworms and describes charms for their removal. the Sushruta Samhita. Scribonius Largus. Moreover. A variety of techniques have been used down the ages in diverse places in an attempt to deal with these mythical creatures. contains prescriptions for the treatment of teeth with worms in them 101. her tears flowing. It seems likely that these ideas arose spontaneously and independently in different places althoug h Townend96 has suggested that this notion ma y have begun in the Nile valley and spread from there to other communities. Similarl y. Such ideas were also prevalent in Mesopotamia. Many herbal remedies have been employed but the pride of place goes to henbane ( Hyoscamus species). the tablet described the origins of these worms and their modus operandi: After Anu made the heavens. the Syriac Book of Medicine. Likewise. physician to the Roman emperor. constituents of henbane. hyo scyamine and related drugs. A seventeenth centur y English poem mentions come of these: If in your teeth you hap to be tormented. 8 In many instances. Thus. By means some little wormes therin do breed. caterpillars . This approach was based upon the belief that toothworm infection was associated wit h invasion and possession by a demon which could be driven out by invocation. tamarisk.e. when as you feede. Toothworms and toothache to be placed under the earth. As well as plants. Which pain (if heed be tane) may be prevented. weevils.9 Many of the toothache incantations had a Christian flavour: Abraham said to Jesus Christ As they walked on the slope of Bethris: 'I have not the power of walking Or of riding because of toothache' Said Jesus Christ to Abraham: 'Toothache will not be in that head. Little worm. the Assyrian sufferer from toothache was recom mended to crush a caterpillar on the afflicted tooth while a Greek physicia n suggested that earthworms boiled in oil cured toothache. 31 Other plants which have been recommende d from time to time included myrtle. put a black cloth under it. An alternative ploy was to invoke charms and incantations. And with a tunnel to the tooth that's hollow. known on earth. go away And do me no more harm. they cracked open and plant embryos were scattered and mistaken for worms. Burne Francomsence (a gum not evil sented). mingle these together. and ease shall follow.' 10 Besides being spoken. onions. . various small animals including worms. leeks. let it reek into the mouth. Put Henbane into this. work into a wax candle and burn it. it seems that when seeds wer e heated. Out of the toothache! Out of the toothache! Known in heaven. ladybirds and small b eetles were used to "cure" toothache. take acorn meal and henbane seed and wax of all equally much. This seems to have been based upon the principle of "similis similibus curantur". charms were sometimes written on paper or parchment and worn as an amulet. Meanwhile. i. decrease. raisins and roses. Go away from us. and Onyon seed. Known to thy King is thy disease. that the administration of worms or some such would cure the disease caused b y worms in the teeth. Convey the smoke thereof. then will the worms fall on to it. the pagan Brandenburgians supplicated the moon: Little moon. For example.Miscellanea Anglo-Saxon leechcraft: 767 For toothworms. By keeping cleane your teeth. dulled the pain. sumach. Earworms and Nasal Worms There have been many descriptions of worms in the orbital. Or pound and mix together sumach. Andry in 1741 recounted Ettmuller's technique for eradicating such parasites. doubts grew about toothworms. Pierre Fauchard (1690-1761) in his classical work on dental surgery described how he had tried to find these worms and had failed.boil strong onions in the urine of children. Many. Its presence could be "proved" by fastening a small fish to the umbilicus in the evening then noting whether some of it had been "eaten" in the morning.768 A History of Human Helminthology Gradually. however. some of those in the eye may have been true worms (Loa. Umbilical worms This worm was thought to live within the umbilicus of small children and cause weakness and failure to thrive. blepharitis (inflammation of the eyelids) ma y have caused crusts which had the appearance of parasites. Others confirmed his observations and toothworm s passed into the realms of mythology. Thus. were imaginary and have been described by numerous authors since the time of Galen. Moreover..101 Another popular method for driving out the worms was fumigation and i s described under toothworms. for example. parts of the fish had been rubbed off by the movements of the child.. In the case of the orbit. Eyeworms. goat's milk. and raisins with honey. Jacques Houllie r (1498-1562) wondered whether they really existed and condemned th e widespread practice of fumigations (cited in 52). rings of pomegranates. som e enterprising quack "eye-specialists" have been known to breed fly larvae then insert them into the conjunctival sac thus permitting their removal from tha t site16. heat the mixture and drop it into the ears. aural and nasa l cavities. the Syriac Book of Medicine remarked concerning: Worms in the ears. Thelazia). and drop the liquor into the ears. Or pour juice of absinthe and old oil which is cloudy into the ears and the worms will come out. Half of a nutsh ell containing a mixture of honey with . In reality.. . Many techniques have been described for flushing worms out of thes e domains and indeed may be the means of producing objects resembling worms. however. Indeed. Some of these may not have been imaginary at all as it is well-known that flies may deposit eggs in these places from time to time and the resultant maggots may have been mistaken for worms. Urine Worms Macroscopic worms have rarely been passed in u rine but sometimes coagulated blood in elongated form has been mistaken for worms. Furthermore.Miscellanea 769 powdered glass and juniper is fastened to the umbilicus then "the worm comes as usual and attracted by the honey eats of this mixture from which it dies" 3. 6. a centipede. Fourth generation: a ball of thread. an ant. Second generation: a ball of hair. the lungs of a pig or a snake. the t ail of a horse or a bird. Echoing Worms In ancient China. they were thought to undergo transformations in their appearance during six generations. It was believed that they began their life with the birth of their host.000 of these worm s were present in each human body and that without them the human body could not exist. a grub. It wa s thought to be carried by the wind and be found in northern Sweden. 4. a hedgehog or a caterpillar. For similar reasons. For example. Third generation: a mosquito. Furthermore. Ku Chin Yi T'ung Ta Chu'an described and illustrated the following: 1. Furia infernalis (Höllenwurm. horse s and cattle in summer and cause . A rather similar worm was the "Amao" described by Lusitanius (1575-1642 ) which was supposed to live in the intestinal canal of children and graduall y consume their strength so they died if the worm was not expelled by the proper treatment72. In ancient China it was believed that up to 80. Corpse Worms These worms were also sometimes known as "food worms" or "phthisi s worms". a mantis. Fifth generation: a hairless mouse. some Chinese anthelmintic prescriptions required that silence should be maintained while preparing the medicines otherwise the worm may hear and not be expelled 54. The parasite was supposed to be a very small worm. It was said to attack humans. These worms were thought to be expelled or killed when th e relevant part of the Chinese pharmacop oeia was read and the appropriate herbs taken. 3. Worms of the first generation: resembled an infant with hair on its back. 5. yellowish-white in colour with one dark end. a ghost or a frog. the thickness of a hair. a lizard. Mordwurm) This parasite was listed by Linnaeus in his Systema Naturae and discussed by 79 a number of writers including Solander 90 and Pallas . it was believed that worms of this generation had either wings or feet and could therefore reinfect people at a distance of a thousand miles 64. Sixth generation: a tortoise. and have a single row of minute spines. 2. a shrimp or a crab. Lapland and Russia. it was sometimes believed that people were made sick b y echoing worms which were supposed to produce an echo when the parasitized person spoke. or escaped in some othe r way. frequently worms. more properly. these are usually confuse d with entomological ectoparasites. glanders. This condition may be seen in the setting of a primary psychiatric disorder or in conjunction with a variety of organi c illnesses including vitamin deficiencies. passed in stool o r urine. a physician in Florence: A worm the size of four fingers. central necrosis and death within several hours to days.80 In addition. Those with primary psychiatric disorders may have parasitophobia as an isolated problem while in others it is part of a schizophrenic. hydatidiform moles in the vagina27 and even spermatozoa 69. It is likely that in fact the writers were des cribing a number of bacterial diseases such as anthrax. depressive or compulsive illness. described and illustrated numerous fantastic creatures that had allegedly developed i n abscesses or had been passed from the gut. Thus. it had a body covered with downy hair. plants have also been thought to be worms. many pseudoparasites wer e free-living animals that were thought to be found in the human stomach and intestines . Others are quite inexplicable in this way such as the extraordinary claims that a Russian vomited a dog and that a young boy passed a pup in his faeces 58. salamanders. Others are certain that they are infected with internal parasites. For example . Seltzer of Strasbourg in a thesis described "worms" which h e found in the stools of a 26 year old woman that turned out to be the seeds o f Morus nigra 92. or in abscesses. Normal or pathological human structures have al so been mistaken for worms. with a red round head the size of a large weight. This was followed by the development of a painless swelling. These include the secretions of sebaceous glands 3. They were supposedly vomited. Thus. a famous French military surgeon.770 A History of Human Helminthology a burning feeling like a mosquito bite. For example. PARASITOPHOBIA Parasitophobia or. tularaemia or plague 54. . leeches and lice. These included frogs. Ambroise Paré (1510-1590). snakes . mendicants o r charlatans. Some patients are convinced that they harbour parasites in the skin. a delusion that a person is infected wit h parasites was apparently first described in 1872 (cited in 104). Besides members of the animal kingdom. chronic renal failure and toxi c psychosis. a bifid tail in crescent shape and altogether four feet. the urinary bladder. he cited a specime n recovered from a patient by Benenius. lizards. the female genital tract. an Ascaris may look like a snake to the uninitiated . Some found their way into human excreta by chance while others were placed there by hysterics. two before and two behind. PSEUDOPARASITES Pseudoparasites seemed just as real as imaginary parasites. illustrations were produced with the aid of woodcuts but during the seventeenth centur y copper engravings which permitted the renderin g of finer details were gradually introduced. Edward Tyson illustrated the anatomy of Ascaris lumbricoides 97 then in the same year he drew a Taenia saginata and reproduced the scolex of a dog tapeworm98. Velschius in 1674 showed Dracunculus medinensis protruding from various parts of the human body but gave no details of the parasite 100.Miscellanea 771 Wykoff104 reviewed cases reported in the literature and added many of hi s own. SEVENTEENTH CENTURY The liver fluke. He remarked that this condition is seen most frequently between the ages of 40 and 60 years and occurs more commonly in females. In 1683 . presumably Ascaris. The first simple illustration of a tapeworm (without a head) was provided by Cornelius Gemma in 1575 46. Spigelius (van der Spiegel) 91. and the dog and cat tapeworms. He also drew filariae obtained from birds. in 1491. was figured by Redi in 1668 82 then by Ruyschius in 1691 86 and Bidloo in 1698 13. In 1596. This book had 1066 illustrations with one of them showing a man in a squatting position from whose anus large worms. Germany. EARLY ILLUSTRATIONS OF WORMS Very few worms parasitic in humans we re known when printing became established in Europe in the latter half of the fifteenth century. Clericus 29 and Andry3. Tyson illustrated Cysticercus tenuicollis from the omentum of an antelope99. . the reproductive organs of Ascaris lumbricoides. This picture was copied by many author s including Aldrovandi 1. Cysticercus pisiformis . Response t o treatment has been poor. Redi described 108 different parasites an d produced copper plates in wh ich he illustrated amongst other things Eustrongylus gigas. In the early nineteenth century the new technique of lithograph y was adopted. The Dutch explorer van Lins choten illustrated the extraction of a Guinea worm70. Fasciola hepatica. In the following year. were passing out (cited in28). Initially. each of the latter with a head 83. In 1691. FIFTEENTH AND SIXTEENTH CENTURIES Perhaps the first illustration of a parasitic worm is to be found in the Hortus Sanitas of Jacob Meydenbach published in Ma in. Included amongst them was a reproduction of Enterobius vermicularis by Contoli who had regarded it as a minute fish. Clonorchis sinensis was drawn by McConnell in 1875 73 then a figure of an adult Wuchereria was published by Cobbold in 1877 30 from material provided by Bancroft. Brera (1811) 22 and Bremser (1819)20. worms were supposed to be passed in the stools: Abdominal pain in children accompanied by a palpable mass in the abdomen is due to worms. respectively. In this case. Roederer and Wagler 84 provided a simple drawing of Trichuris trichiura. Moxibustion In this procedure. A variety of worms were illustrated in 44 plates 17 by Goeze in 178248 and in 10 plates by Bloch in the same year . Owen drew the larvae of Trichinella spiralis in 183578 then Dubini illustrated Ancylostoma duodenale in 184337.56 This practice is based upon the theory that the inserted needles will transfe r energy to different parts of the body along hypothetical lines or "meridians". Crude drawings of the worms sub sequently called microfilaria bancrofti and microfilaria volvulus were made by Demarquay (1863) 36 and O'Neill (1875)77 . no drug is necessary: simply advise the parents to massage the abdominal mass for half a day. cones of the plant Artemisia (worm-wood) are applied to . NINETEENTH CENTURY Good illustrations of a number of worms were provided by Joerdens (1801) 58. Schistosoma haematobium was figured by Bilharz in 1852 14. In 1762.772 A History of Human Helminthology EIGHTEENTH CENTURY Andry gave illustrations of fragments of Taenia and Diphyllobothrium in 17002 and again in subsequent editions of his book in 1718 and 1741 3. Fischer drew Cysticercus cellulosae in the choroid plexus 42.25 Acupuncture Acupuncture has been practised in China as a means of treating worms for many years: Heartache caused by the three kinds of worms is attended by profuse salivation and inability to turn the body into a recumbent position. The last author illustrated Coenurus and Echinococcus. In 1789. UNORTHODOX MODES OF TREATMENT Massage Massage of the abdomen has been recommended for the treatment of intestinal worms in many countries but particularly in China. As a consequence of this procedure. This kills the worms which will be passed out in the faeces. Clericus in 171529 copied the figures of previous authors in 14 plates. the pit of the stomach is the proper place for acupuncture. In this case. Küchenmeister. particularly upon the efficacy of anthelminti c therapy. Some authors believed that the moon also i nfluenced symptomatology. He treated 100 persons with intestinal worms during the days of the wanin g moon and found that more than 80% were cured. He advised that anthelmintics be given only during the waning of the moon 76. THE MOON AND WORMS For many centuries and in many parts of the world. One of the first authors to deal with this subject was Nicola s Myrepsus. Rosen de Rosenstein85 thought that the symptoms were worse in children wit h tapeworm infections during the waning moon and at the time of the new moon. Further. Such ideas were not confined to Europe. Many of the incantations had quasi-religious overtones while charms were objects with written or engraved magic signs or words. gave some credence to the phenomenon. Andry at the beginning of the eighteenth century was sceptical at first about such an effect but then. Magic In diverse countries down the ages. Music Music was advocated occasionally for the treatment of worms in Europe in the eighteenth century. Wawruch 102 claimed that Taenia segments appeared in stools more regularly at this period. they thought tha t anthelmintic therapy was more effective if the head of the worms was turned upwards 54. Some authors contended that Ascaris was more likely to be discharged around this time and believed that there may be a simila r influence on Enterobius. sought a relationship between the numbers of worm s discharged and the phases of the moon but could find no connection 63. the moon has been held to have an influence on worms. the result wa s reversed if the therapy was given on the other days 2. however. Hoffman55 advised giving anthelmintics when the moon changed its phase. The smouldering fire burns into the skin and produces a blister. it has been the practice t o administer anthelmintics when the moon is full 68. . tapeworms could be expelled by the noise of a Jew's harp. magic in the form of incantations o r charms has been invoked to induce the expulsion of intestinal worms. a Greek physician who lived in the thirteenth century. Some ea rly Chinese writers believed that intestinal worms had their heads turned upwards during the first half of the lunar month and downwards in the second half. It was sometimes used in China as an anthelmintic measure 54.Miscellanea 773 the skin and ignited. who was infected with these las t parasites. In recent times in Ruanda in Africa. In contrast. Similarly. According to Goeze 48. Others believed that intestinal worms could sens e sound and recommended the use of certain musical instruments to mollif y tapeworms and thus relieve symptoms 21. following an investigation. Likewise. baked dry over a tile on a fire. 89 WORMS AND IMMUNITY In 1862. Both of these aspects interact and ultimately ar e determined genetically.in whichever animal supplies these conditions. Syngamus trachealis. but the embryo only hatches when it is brought by food or drink. it will help enlarge and stiffen the penis and prolong its periods of erection.. he took ov a of the common roundworm of humans. He failed subsequently to find adult worms in the intestine of these animals and concluded that. and ground into a powder will. Likewise.. mix with grease and roll into pills of the size of barley seeds. has from time time been a popula r therapeutic device in both the Occident and the Orient. Despite over 100 years of investigation since the time of Davaine. we are little wiser as to the reasons why these variations in hos t responsiveness occur or as to what the mechanisms are by which suc h responses are generated. they were not susceptible hosts to this parasite: Eggs of A. Before coitus.. it has been shown with a number of parasites that the sex of the host influences the susceptibility to infection with male animals in general being more prone to infection. It was even used as an aphrodisiac: Grind the above (Ascaris) into powder.e. while old chickens were difficult to infect. first to a cow. however. the development of resistance to a particular parasite following prior exposure was floated by Weinberg and Julien in 1911 103.the host specificity of a parasite and the parasite fauna characteristic of a given host species. This probably applies to human s although it has never been definitely shown. A variation on this theme is the effect of age on susceptibility to firs t infection. then to rats. the egg hatches if it remains in the intestine long enough. The idea of acquired immunity to a worm. Ascaris lumbricoides. washed clean. In China.g. lumbricoides develop outside the body of man. cancrum oris and boils e. Pulverized. Casimir Davaine highlighted the phenomenon of natural resistance to helminth parasites.774 A History of Human Helminthology WORMS AS THERAPEUTIC AGENTS The roundworm. drie d worms were commonly used by both the medical profession and the populace at large in Europe as an anthelmintic.35 The accumulation of such data led to the development of two important concepts . introduce one pill into the urethra. "An Ascaris worm. when applied to pustules and furuncles. effect a quick cure" 26. the embryo does not linger if the animal is not of the kind where the worm can acquire its final form. Ascaris lumbricoides. This phenomenon was alluded to by Looss in 191171 then Ransom in 192181 observed that young chickens were infected easily with the gapeworm. i. worm extracts were recom mended for the treatment of a wide range of conditions such as ulcerativ e blepharitis. They carried out experiments on ascarid infections in horses . i n contrast to humans. and fed them. anal fistula. painful ophthalmitis. hay fever and eczema. saginata infections. Whether significant acquired immunity develops in most human helminth infections has been a matter of intense debate ever since. Fujinami in a paper entitled (in translation) "Immunity t o macroparasitic disease: can it be acquired?" recorded the acquisition o f immunity against Schistosoma japonicum in horses45. In the same year. with the probability being that i t develops only to a limited degree 50. In the following year. Blackwell and Thompson in 1923 observed that immunit y could be acquired by both man and animals against the larva of the tumbu fly. The relationship between helminthiasis and the atopic d isorders. which causes cutaneous larva migrans 15. the development of acquired immunity against Trichinella spiralis was shown in rats by Ducas38. The era of immunodiagnosis in human helminthology was probably ushered in by Isaac and von den Velden in 1904 when they reported th e presence of a precipitin reaction in the serum of a person with Diphyllobothrium latum infection and compared this with a negative in an uninfected 43 control individual57. Reactions to ascarids were described by Miram. Cordylobia anthropophaga. Bastian. How worms manage to evade the host' s responses and persist has been a subject of earnest but largely unproductiv e speculation18. In 1910. Five years later. solium or T. Ghedini described a complement fixation test for antibody directed against fluid from human hydatid cysts 47. has been a thorny one for many years. Fleckseder and von Stejskal found antibodies against Taenia saginata in the serum of immunized rabbits bu t Langer65 could not find such antibodies in humans infected with T. Fleig and Lisbonne 44 described a test for precipitating antibody i n echinococcosis.Miscellanea 775 and concluded that horses infect ed with a certain number of parasites gradually immunized themselves against the actio n of the secretions of these worms. Sophisticated immunological techniques have been developed in recent years and are no w frequently being employed in the immunodiagnosis of human helminthiases 7. Huber. Gold schmidt again described features r esembling hay fever after exposure to human and horse Ascaris and recognized its allergic nature49. In 1921. Herrick in 1913 may have been the first t o recognize an association between asthma and worm infection when he wrote: Common to both bronchial asthma and Ascaris infection is an increase of the eosinophils in the blood.53 . The development of immune responses. particularly the appearance of antibodies and skin reactivity has been put to diagnostic purposes for man y decades. Leuckart. In 1906.32 but success has hitherto eluded everyone's grasp. Railliet and many others in the nineteenth century. In 1911. Casoni described a skin test for echinococcosis in which delaye d hypersensitivity reactions occurred in infected persons after intraderma l injection of fluid obtained from a sheep hydatid cyst 23. asthma. The possibility of developing vaccines against helminths has now been floated for a number of years 6. One may well ask the significance of the eosinophilia in this association. Cobbold. and cancer: Even in certain tumours the role of the entozoa would appear very probable. under the auspices of the Cancer Field Commission of the Tropica l Disease Prevention Association. Nevertheless. A number of hypotheses wer e advanced including a belief that worms caused asthma. the concept that worm infection ameliorated asthma. he observed increased levels of the same antibody i n Ethiopian schoolchildren with Ascaris infection60. WORMS AND CANCER Eli Metchnikoff. in rats from the West Indies and South America caused cancer of the stomach and suggested tha t cockroaches may be the intermed iate hosts39... The first major textbook of helminth immunology was written in 1929 b y Taliaferro who produced a 414 page work entitled The immunology of parasitic infections "94. Similar elevations were then seen in a variety of helminth infections. the generally-recognized discoverer of the phenomenon o f phagocytosis. indeed by any. Nevertheless.41. now IgE) and found that increased levels were seen in the serum of patients with asthma. These discoveries provided a further nexus between helminthiasis and atopy.Might not the entozoa serve as gates for entry for the hypothetical parasites of those tumours?74 He drew attention to the recent studies of Borrel 19 who had described the presence of intestinal worms in the centres of intestinal tumours of mice an d had correlated cysticercosis and tumours in rats. This was followed in 1941 by Culbertson with hi s Immunity against animal parasites "33. Spirometra neoplastica (= Gongylonema neoplasticum). in particular intestinal worms. this idea was taken up by enthusiasm by Sambon and Bayliss who. Metchnikoff then went of to advocate a campaign against intestinal worms in order to prevent cancer in the same manner as the war which had just begun against disease-carryin g insects74.4 Nevertheless. Fibiger in Copenhagen claimed that a newly-recognized worm . in his Harben Lectures of 1906 advanced the proposition tha t there may be a relationship between entozoa. still less that cancers of higher animals and man are produced by a similar. Similar findings were then made in other worm infections. parasite. In the following year. investigated the relationship betwee n . and the proposition that atopic individuals ar e able to generate increased resistance to worms 51.. He revived this idea in 1920 with further studies40. In 1913. an editorial writer in the British Medical Journal cautioned: It must not be assumed that spontaneous tumours of rats and mice are commonly caused by the ingestion of food containing Spiroptera neoplastica. little attention was paid to this association until Johansson in 1967 59 discovered a new class of immunoglobulin (initially called IgND.776 A History of Human Helminthology Paul Erlich had described these peculiar white cells in 1879 then Müller and Rieder in 189175 observed that they were increased in number in hookwor m infection. British Medical Journal 283 : 1349-1350. Avec trois lettres sur les sujets des vers. 1700.. translated by H Rhodes and A Bell. Gongylonema and cancer. BAYLISS HA. pp 468.88. This hypothesis was attacked by Leiper and a heated correspondence followed 11. Fibiger's tumour of the rat's stomach. Paris. ANONYMOUS. BERDOE E. British Medical Journal ii: 503-504. De animalibus insectis libri septem denuo impressum.67. Cited in 12 9. Cited in 61 10. pp 509. Laurent d'Houry. Nevertheless.. ANONYMOUS. 1602 2. 1701 3. 1741. pp 767. Postumius A.. Helminths in cancer. and Clonorchis sinensis and carcinoma of the bile ducts (se e chapter 6) THE GOD.par M .. REFERENCES 1. 1981 8. 1960 7. son of Aulus grandson of Aulus Duovir by the Plaetorian law" Apparently. "VERMINUS" The Romans apparently had a god of worms and worm diseases name d "Verminus". les deux premières. Immunisation against helminths.par M. Lauren t d'Houry.. ANONYMOUS. 1938 6. Bononiae. pp 266. British Medical Journal i: 777-778... Immunodiagnosis in parasitic diseases. ALDROVANDI U.N Albi Duovir lege Plaetoria" which has been translated as: "To Verminus Aulus Postumius Albinus. Ferronius . Swan Sonnenschein and Co.F.A. ANONYMOUS. 1920 5.Schistosoma haematobium and bladder cancer (see chapter 8).Miscellanea 777 Gongylonema and cancer in certain districts in Italy. 1926 12. Lancet i: 735-736. Cited in 96 11. Partly translated in 54 4. A popular history of medicine in all ages and countries. Leiper was proven correct when it was finally concluded that Fibiger's tumours were in fact non-malignant 5. 1893 .. The little that is known about this deity derives from an inscription on an altar found near Rome in 1876. resulting in cancer 87. ANDRY R. ANONYMOUS. The origin and growth of the healing art. De la génération des vers dans le corps de l'homme. This led to the concept of "cancer houses" with the theory that Gongylonema was transmitted from person to person by cockroaches. pp 1190. Nicolas Hartsoeker et l'autre. ANONYMOUS. In the event. De la génération des vers dans le corps de l'homme. time has been a little kinder in favouring associations between cancer and two parasites . Georges Baglivi. Aulus 54. The inscription said: "Vermino A. third edition. ANDRY R. Paris. 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La diagnosa biologica dell'echinococcosi umana mediant e l'intradermoreazione. Carl Schaumburg et Comp. Crema. CULBERTSON JH. 1750. série 3. second edition. Compendio di elintografia umana. In Chinese. 1941 34. au s brieflichen Mittheilungen des Dr. Immunity ag ainst animal parasites. Abhandlung von der Erzeugung der Eingeweidewürmer und den Mittel n wider dieselben. Charlatans et pseudo-parasites: les "vers des yeux". 1852-1853 15. BLOCH ME. Knopf. BIDLOO G. Comptes Rendus Hebomadaires des Séances de l'Académie des Sciences. London. pp 1192. Bilharz in Cairo. C. 1918 17. THOM PSON MG. BRERA VL. Fratres de Tournes. pp 838. COX FE. wort cunning and starcraft of early England etc. Bulletin de l'Académie de Médecine de Paris 41: 141-144. BREMSER JG. Traité des entozoaires et des maladies vermineuses de l'homme et de s animaux domestiques. Columbia University Press. Krumbhaar.778 A History of Human Helminthology 13. Lancet ii: 495-496. BLACKLOCK DB. . Lugduni Batavorum. Napoli. DAVAINE C. Translated from the Italian and edited by E.. Leipzig. 1877 31. 1860 35. nebst Bemerkungen von Prof. CASONI T. Zeitschrift für wissenschaftliche Zoologie 4: 53-76.). Games parasites play: how parasites evade immune surveillance. 1715. three volumes.) In Chinese . Nebst eine m Anhang über Pseudo-helminthen. pp 436. A history of medicine. Genevae. delle CHIAIE S. Nature 273: 623-626. translated by J Browne. 1819 21. pp 274. Ueber lebende Würmer im lebenden Menschen. DAVAINE CJ. Translated in 62 . Aus dem Italienischen uebersetz und mit Zusaetzen versehen von FA Weber. Paris. 1803 22. Observatio. Longman. Wien. Antonio Ronna. Nature 279: 21-26. 1858 29. Leipzig. 1978 33. BLANCHARD R. nascentium etc. Ein Buch für ausübende Aertze. 1864-1866 32. J B Baillière et fils. CHOULANT L. 1906 20. Cordylobia anthropophaga Gruneberg in Sierra Leone. pp 449. von SIEBOLD CT. COCKAYGNE O. Sigismund Friedrich Hesse. What is the relationship between asthma and worms? Allergy 37: 139-148. In. Singapore. Experimental eosinophilia with an extract of an animal parasite: it s relation to anaphylaxis and certain clinical features. 1982 52. GOLDSCHMIDT R. two volumes. Méthode pour la production expérimentale du cancer. 1906 48. (Immunity to macroparasitic disease. Biologische Reaktionen mit Bandwurmextrakt. 1904 58. GROVE DI. GEMMA C. JOHANSSON SG. J Haasio. pp 526. GHEDINI G. FLECKSEDER R. 1913 54. Comptes Rendus Hebdomadaires des Séances et Mémoires de la Société de Biologie 83: 692-695. Versuch einer Naturgeschichte der Eingeweidewürmer thierischer Körper . Ricerche sul siero di sangue di individuo affetto da cisti da echinococco e sul liquid in essa contenuto. University of Malaya Press. Nuovo verme intestinal umano ( Agchylostoma duodenale ) costituente un sesto genere dei nematoidei proprii dell'uomo.E. Berliner klinisch e Wochenschrift i: 289-298. FLEIG C. Recherches sur un sérodiagnostic du kyste hydatique par l a méthode des precipitins. Symons. Immunological studies of an atypical (myeloma ) immunoglobulin. Partl y translated in 54 57. L. LISBONNE M. FIBIGER J.) In Chinese. FIBIGER J. von STEJSKAL K. von der VELDEN. Lea and Febiger. HERRICK WW. Immunity in human helminth infections. De naturae divinis characterismis seu raris et admirandis etc. FIBIGER J. Helminthologie. Thèse. (The classics of acupuncture and moxibustion. Sur la transmission aux rats de la Spiroptera neoplastica (Gongylonema neoplasticum). Genevae.Miscellanea 779 36.K. Carcinome spiroptér ien de la langue du rat. 1863 37. 1843 38. n) hervorgerufene papillomatöse und carcinomatöse Geschwulstbildung im Magen der Ratte. HOEPPLI R. 1789 43. GUERINI V. 1740-1753 56. Abstracted in China Medical Journal 31: 81. Entomologie und Helminthologie des menschlichen Koerpers etc. MELLBIN T. pp 355. Die Aska risvergiftung.D. JOERDENS JH. 1904 44. Parasites and parasitic infections in early medicine and science. pp 375-400. Münchener medicinische Wochenschrift 57: 1991-1993. 1982 51. 1920 42. JOHANSSON SG. Immunology 13: 381-394. HUAND-FU MI. Gazzetta degli Ospedali et delle Cliniche 27: 1616-1617. ISAAK S. Taeniae hydatigenae in plexu chorioideo nuper inventae historia etc. pp 508. VAHLQUIST B. 1967 60. 1917 46. PA Pape. Paris. Gazette Médicale de Paris 18: 665-667. Sydney. A. 1782 49. Annali Universali di Medicina 106: 5-13. Philadelphia. HOFFMANN FH. BENNICH H. can it be acquired?). Lancet i: 1118-1121. FISCHER JL. et supplementa. 1801-1802 59. G A Grau. Hof. Comptes Rendus Hebdomadaires des Séances et Mémoires de la Société de Biologie 62: 1198-1201.. FUJINAMI A. Eine spezifische Präzipitinreaktion bei Bothriocephalus latus behergergenden Menschen. 1921 39. 1920 41. Academic Press . Deutsche medizinische Wochenschrift 30: 982.. pp 471. Antverpiae. Archives of Internal Medicine 11 : 163-186. GROVE DI. Donald and J. I n Japanese. DEMARQUAY JN. Blankenburg. Ueber eine durch Nematoden ( Spiroptera sp. pp 473. 1909 53. DUBINI A. Biology and control o f endoparasites. L'immunité dans la trichinose. 1907 45. DUCAS R. pp 225. 1968 . 1575 47.. Lipsiae. Dineen (Editors). Comptes Rendu s Hebdomadaires des Séances et Mémoires de la Société de Biologie 83: 321-324. 1910 50. 1916. 1959 55. Wiener klinische Wochenschrift 17: 793. Opera omnia physico-medica etc. Immunoglobulin levels in Ethiopian pre-school children with special reference to high concentrations of IgE (IgND). Jouve et Cie. A history of dentistry from the most ancient times until the end of th e eighteenth century. 1913 40. GOEZE JA. Partly translated in 54 81. 1921 82. l. Tropical medicine and parasitology. A manual of their natural history. pp 244. LESTRADE. Piero Matini. Chez Pierre Rigaud. BG Teubner. Ithaca. United States Department of Agriculture Bulletin No. PARÉ A. 1875 74. Classi c investigations. 1906 75. REDI F.780 A History of Human Helminthology 61. Lancet ii: 271-274. Lancet i: 265-266. 1978 63. 1857 64. 1599. WAGLER CG. fasc. 1778 86. Teucrides Annaeus Lonicer. On animal and vegetable parasites of the human body. Animal parasites belonging to th e group Entozoa. Esperienze intorno alla generazione del'insetti. Carlo Dati. 1926 68. Les oeuvres d'Amroise Paré. Zoologische Bruckstucke. 1684 84. Goettingae. Zur Frage der Bildung spezifischer Antikörper im Organismus vo n Bandwurmwirten. De antid. 1691 87. Egyptian Ministry of Education 4: 163-613. B Bossigelium. I. LARGUS S. pp 677. pp 452. On the presence of a filaria in "craw-craw". tant l'anatomie que des instruments de chirurgie. 1835 79. Avec les voyages qu'il a faits en divers lieux: et les pourtraits & figures. 1905 66. Traduit du Suédois par Le Febvre de Villebrune. The Syndenham Society. Freiburg. Bruxelles. 1925). 1955. RUYSCHIUS (RUYSCH) F. MOTT KE. OWEN R. PALLAS PS. II. 939. The development in the free state. Cited in 54 69. H et T Boom. 1668 83. LOOSS A. & de plusiers monstres. Paris. ROEDERER JG. 1819 70. im circulirenden Blute des Menschen. two volumes. The hygiene of the alimentar y canal. quem nupe r speciminis inauguralis loco ediderunt. O'NEILL J. pp 177. 1781 80. onzième edition. (Ethnographie). KÜCHENMEISTER F. Osservazione intorno agli animali viventi che si trovano negli animali viventi . 1762 85. sect. translated by E Lankester. Cited in 52 67. van LINSCHOTEN JH. RIEDER H. McCONNELL JF. LEIPER RT. 1926 62. pp 138. 1651. three volumes. La médecine indigène au Ruanda. Ein Lehr. 1891 76. tome VIII. Part II. Münchener medizinische Wochenschrift 52: 1665-1665. 298. Frankfort . Lyon. Translated from the German by M Bernhard. A monograph. Die in und an dem Körper des lebenden Mensche n vorkommenden Parasiten. Hugonis Lintscotani navigatio in orientem etc. The Harben lectures for 1906. Firenze. Journal of Tropical Medicine and Hygiene 29 : . LUSITANIUS. Leipzig. P G Cavelier. 1855. MYREPSUS N. London. Observations and researches o n epidemiology of cancer made in Holland and Italy (May-September. Traité des maladies des infans etc. Cited in 29 73. Firenze. MÜLLER HF. Cornell University Press.. LEUCKART FS. De morbo mucoso liber singularis. KEAN BH. Neue nordische Beyträge physickalische und geographische Erd. Stuttgart. Deutsche Archiv für klinisch e Medicin 48: 96-121. London Medical Gazette 16: 125-127. Ehrlich. 1596 71. The anatomy and life h istory of Agchylostoma duodenale Dub. Description of a microscopic entozoon infesting the muscles of the huma n body. Cited in 54 65. Dental Cosmos 67: 259.und Volkerbeschriften 1: 113-131. cap. Académie Royale des Science s Coloniales. LANGER J.. Nouvelle série. Folklore of the teeth. KU CHIN YI T'UNG CHU'AN. pp 582. SAMBON LW. Amstelodami. Einige Erinnerungen die Bandwürmer bettrefend: in Beziehung auf de s zwölfte und vierzehnte Stück des N aturforschers. Records of the School of Medicine. 1875 78. ROSEN de ROSENSTEIN N. RUSSELL AJ. REDI F. Observationum anatomico-chirurgicarum centuria etc. Original Dutch edition. KANNER L. 1911 72. Ueber vorkommen und klinische Bedeutung der eosinophilen Zellen. pp 854. British Medical Journal ii: 504. Classe des sciences morales et politiques. pp 211. Vera descriptio regni pars Indiae orientalis in qua Johann . Remarks on the anatomy and pathological relations of a new species of liver-fluke. pp 486. Volume 1. Gongylonema and cancer. Lancet i: 1554-1555. RANSOM BH. METCHNIKOFF E. Cited in 35 77..und Handbuch der Diagnose und Behandlung de r thierischen und pflanzischen Pa rasiten des Menschen. diagnosis and treatment. Theophili Goebelli. concerning African schistosomes. Delusions of parasitosis: a review. 1691 100. 1618 92. or imperfect animals. TYSON E. Journal of Tropical Medicine and Hygiene 29: 314-322. Nova Acta Regiae Societatis Scientarum Upsaliensis 2: 44. Comptes Rendus Hebdomadaires des Séances et Mémoires de la Société de Biologie 70: 337-339. Pro ceedings of the Royal Society of Medicine 19: 29-78. 1638. 1913 102. pp 414.Miscellanea 781 233-287.R. 1926 89. two volumes. Partly translated in 54 90. Philosophical Transactions of the Royal Society 13: 113-144. Refutation of statements made by Professor R. Gazette Médicale de Paris 9: 633. Philosophica l Transactions of the Royal Society 17: 506-510.D. Bulletin of the History of Medicine 19: 37-58. Extracted from Medizin Jahrbuch des Oesterreich Staates 103. TYSON E.". L Pasquati. THOMPSON RC. WALLIS BUDGE EA. In Chinese. 1683 99. F. are a species of worm. SUSHRUTA SAMHITA. zoo vermin and Italian cancer houses. WAWRUCH. pp 88. 1926 96. Reviews of Infectious Diseases 9 : 433-437. descripti . D. WEINBERG M. SULTZER C. Lumbricus latus. De lumbrico lato liber cum eiusdem lumbrici icone et notis. SOLANDER DC. The Century Co. SAMBON LW. TYSON E. Calcutta. VELSCHIUS GH. Furia infernalis. of the joynted worm etc. (Essentials of Hygiene. A curious book on coitus. 1842. Leiper M. Dissertation sur un ver intestinal nouvellement découvert et décrit sous le nom bicorne rude.Sc. JULIEN A. Strasbourg. 1911 104. edited by Kaviraj Kunja La l Bhishagratna.T. An English translation. Philosophical Transactions of the Royal Society 13: 153-161..).S. 1801 93. pp 52. The immunology of parasitic infections. "American Gongylonemes". pp 456. "The book o f medicines etc. 1944 97. 1929 95. 1683 98. or some anatomical observations on the round worm bred in human bodies. Lumbricus teres. WYKOFF RE. JA Fischer. The story of the toothworm. ad mentem Ebnsinae sive dracunculis veterum etc. or a di scourse read before the Royal Society.. 1926 88. Ne w York. Oxford University Press. Lumbricus hydropicus: or an essay to prove that Hydatides often met with in morbid animal bodies. Sub stances toxiques de l'Ascaris megalocephala . 1775 91. 1674 101. SPIGELIUS (van der SPIEGEL) A. Assyrian medical texts. TALIAFERRO WH. 1911 94. Exercitatio de Vena Medinensi. Syriac anatomy. SHÊH SHENG TSUNG YAO. Augustae Vindelicorum. London. TOWNEND BR.. pathology and therapeutics or. 1987 .. Réflexions tirées de deux cent six o bservations de ténias. vermis et ab eo concitari solitus morbus. . at Neuwied in Germany. 50 AD) Aretaeus was born in the Roman province of Cappadocia in Asia Minor. His work. It was published in 1623.Chapter 29 BIOGRAPHIES ALEIXO de ABREU (1568-1630) Aleixo de Abreu was born in Alcáçovas. De causis et signis morborum [On the causes and signs of diseases]. He studied medicine at Alexandria in Egypt and became a prolific writer. In 1604 he went to Brazil with the governor of that province. a position which he held until 1629. He also wrote on phlebotomy and helminthology. one year after the last edition of his textbook on helminths. probably in the first century AD. (Treatise of the seven diseases). He graduated in medicine from St. and indeed coined the word which is derived from the Greek words referring to straightening and the rearing of children. the son of an ophthalmic surgeon and lecturer in the medical school. amongst other things. During this period he developed dysentery and jaundice which necessitated his return to Lisbon in 1606. the latter book being an attempt to refute the doctrine of the spontaneous generation of worms. He was educated at the Edinburgh Institution. He died in 1742. Diogo Botello. and described. is the only extant treatise. In 1612 he was appointed physician to the treasury officials. the worms now known as Trichuris trichiura and Dracunculus medinensis. Portugal in 1568. He then studied medicine at Coimba University and graduated seven years later. Scotland. the first text on tropical medicine. He entered Evora University and graduated with a bachelor of arts degree in 1583. He studied medicine then later became professor of philosophy and dean of the faculty of medicine at the University of Paris. He wrote the first textbook of orthopaedics. France in 1658. During a serious illness in 1621 he began writing his Tratado de las siete enfermedades etc. Aretaeus was the first person to describe cardiac murmurs and may have been the first to practise direct auscultation of the chest. having studied ophthalmology under von Arlt in Prague and von Graefe in Berlin. however. He first practised in Lisbon then in 1594 he was appointed physician to the governor of Angola. partly in Latin and partly in Spanish. and at the Universities of Edinburgh. Andrews in 1857 and became a fellow of the Royal College of Surgeons of Edinburgh in 1862. (Plate 2) DOUGLAS MORAY COOPER LAMB ARGYLL-ROBERTSON (1837-1909) Argyll Robertson was born in Edinburgh. NICOLAS ANDRY de BOISREGARD (1658-1742) Andry was born in Lyons. Andrews and Berlin. He died in Lisbon in 1630. (Plate 1) ARETAEUS THE CAPPADOCIAN (c. becoming assistant ophthalmic surgeon 783 . He was a man of letters and made notable contributions to both the humanities and science. St. he devoted himself exclusively to ophthalmic surgery. From the beginning of his career. It was this that led him to define hookworm infection as the cause of much anaemia on the island. He held this post for 35 years until his death in 1940. Switzerland. At the age of 17 he became a pupil of Plato at the Academy in Athens. a post which he held until his death. In 323 BC he was forced to leave Athens because of anti-Macedonian feelings and he died at Chalcis in Euboea in the following year. where he later became professor of pathology.784 A History of Human Helminthology (1867) then ophthalmic surgeon (1870) to the Edinburgh Royal Infirmary until 1897 when he became consulting surgeon. the Thakur of Gondal. The Spanish-American War took him to Puerto Rico where he met then married Maria Asuncion Lopez. USA. he returned to Athens in 335 BC and set up a school in a grove sacred to Apollo Lyceus. He investigated the role of an extract of the Calabar bean (physostigmine) in the treatment of certain eye conditions and in 1869 and 1879 published papers describing the pupillary changes in tabes dorsalis (syphilis) which now bear his name (Argyll Robertson pupil). . biology. He was eventually successful in 1926 and was appointed professor of tropical medicine and mycology. He studied medicine at Königsberg (Kaliningrad). psychology. Macedonia. Subsequently. He wrote many works on a wide range of subjects including logic. ethics. BAILEY KELLY ASHFORD (1873-1934) Ashford was born in Georgetown. the school becoming known as the "Lyceum". Meanwhile. When he retired in 1904. daughter of the Marques de Villar. (Plate 4) MAX ASKANAZY (1865-1940) Askanazy was born in Stalliponen. He joined the United States Army and graduated from the Army Medical School and Georgetown University. by whom he had a son and two daughters. In 1905 he was appointed director of the Institute of Pathology in Geneva. shooter and fisherman. He was a tutor to Alexander the Great who probably endowed a museum which allowed Aristotle to collect botanical and zoological specimens. physics. He died suddenly in Gondal on 3 January 1909. He was a keen golfer. the son of a Greek physician.000 persons. He became president of the Royal College of Surgeons of Edinburgh in 1886 and was awarded the honorary degree of LL. he had been a member of the Rockefeller Commission (on hookworm) to Brazil in 1916 and had sailed with the American Army to France in 1917. he became particularly interested in sprue and in candidiasis. He was at Ponce when a devastating hurricane struck and the Army was left to succour 800. He spent many years trying to establish a school of tropical medicine in Puerto Rico. by the University of Edinburgh in 1897. Around 347 BC he moved to Asia Minor and married Pythias.D. He married Miss Fraser in 1882 but had no children. metaphysics. Germany in 1865. Ashford rose to the rank of colonel in the United States Army. In November 1908 he travelled to India to visit an old friend. he retired to the island of Jersey on account of its milder climate. archer. the son of the professor of surgery there. political science. (Plate 3) ARISTOTLE (384-322 BC) Aristotle was born in Stagira. now in the USSR (Lithuania). He died in 1934 at the age of 61 years. aesthetics and literary criticism. He described the appearances of the adult Loa loa. After a period on the island of Lesbos. His official biography recorded that his zeal. (in present-day West) Germany on 13 January 1849. Thomas's Hospital. he came in contact with some Japanese post-graduate students. but in 1869 he transferred to the University of Leipzig. He was promoted to Staff Surgeon in 1913. In November 1928. and in April 1876 he went to the newly-created medical department at Tokyo Imperial University. Glatton . Cheshire. one daughter dying in infancy. From his youth. He began tertiary studies at the University of Tübingen at the age of 17. he was interested in natural history and travel and became fluent in French and English and read Italian and Spanish. went to Vienna where he became an assistant in pathology.M. (Plate 5) ERWIN OTTO EDUARD von BAELZ (1849-1913) Baelz was born in Bietigheim in Württemberg. clonorchiasis. Subsequently. London and qualified as a member of the Royal College of Surgeons and a licentiate of the Royal College of Physicians in 1906. He married a Japanese woman and remained in that country for the next 29 years. beriberi and leprosy. He qualified as a member of the Royal College of Surgeons and a licentiate of the Royal Society of Apothecaries in London in 1859 then received a doctorate in medicine from the University of St Andrews. he invented a method of disinfecting and deodorizing urinals in ships. Following graduation he . He studied medicine at St. and led the rescue team which found Scott's last remains. Baelz made original observations on paragonimiasis. where he later became professor of medicine.S. near Manchester. In September 1918 he was awarded the Albert Medal for gallantry in saving life at sea following an explosion on H. was left in charge of the base camp. Japan. Atkinson was wounded severely in July 1917 while serving with the Howitzer Brigade in France. He began his medical training as an apprentice of Dr Jeremiah Shaw in Sale. and went with Leiper on his expedition to the Orient in 1914.Biographies 785 EDWARD LEICESTER ATKINSON (1882-1929) Atkinson was born in England in November 1882. the only son of Peter Bancroft and Mary Lane in 1836. kindly disposition and consideration made him a friend to all. Von Baelz returned to Germany in 1905 and died in Stuttgart on 31 August 1913 at the age of 64 years. then returned to Leipzig where he worked for four years under Wunderlich who at that time had the most famous clinic in Germany. but died at sea on 2 February 1929 at the age of 46 years. He joined the Royal Naval Medical Service as a surgeon in 1908. While working there. He was decorated both in Japan and in Germany. He was medical officer to Captain Scott's ill-fated expedition to the South Pole in 1910. England. In May 1918 he was awarded the Distinguished Service Order. Baelz returned to Leipzig then graduated in medicine in 1872. he was gravely injured in the process and his life was despaired of for some time. tact. He then continued his studies at the Manchester Royal School of Medicine and Surgery and at the Manchester Royal Infirmary. the son of a builder. (Plate 6) JOSEPH BANCROFT (1836-1894) Bancroft was born on a farm at Stretford. pluck and determination brought him through many vicissitudes. At the outbreak of the FrancoPrussian War (1870). he was placed on the retired list as medically unfit with the rank of Surgeon Captain. he studied pathology at the Leipzig Polyclinic. versatility. While still a medical student he married Ann Oldfield by whom he had three children. He was a keen bacteriologist and parasitologist. he joined the artillery and became a medical auxiliary. and that his cheery optimism. England. he returned to Brisbane and entered practice. especially snake-bite. making many contributions to knowledge of the Australian fauna and flora. yet on the other hand it has been remarked that he was direct of speech and at times could be rather irascible. He died in New York State. New York in 1913 and attended the London School of Tropical Medicine in 1914. Australia with his family aboard the "Lady Young". typhoid fever. (Plate 8) CLAUDE HEMAN BARLOW (1876-1969) Barlow was born in Lyons. He was educated at Brisbane Grammar School then in 1877 went with his father to Britain to begin training as a medical student in Edinburgh. He became visiting surgeon to the Brisbane Hospital in 1867 then in 1868 he was appointed house surgeon. he was a devoted. Michigan. In 1908. Because of illness (possibly nephrotic syndrome). settling on the outskirts of Brisbane in 1867. (Plate 7) THOMAS LANE BANCROFT (1860-1933) Bancroft was born in Nottingham. He was said to be a kindly and approachable man. He married Grace Hawley in the following year and had four daughters. Two years later he resigned this post and became a visiting surgeon once more and developed a thriving private practice. Following his graduation in 1883.786 A History of Human Helminthology practised in Nottingham for five years. When the meatworks closed in 1904 he returned to Brisbane. He wrote on a variety of clinical topics. He was released by the Society from his other duties in 1922 in order to pursue his researches on fasciolopsiasis in China using facilities provided by Johns Hopkins University. talented and many-sided doctor-naturalist. Australia in 1864. tick paralysis. on 9 October 1969 aged 92 years. He died in 1933. apart from a period spent in South Africa where he also was concerned with schistosomiasis control. He was interested in public health and was for a number of years Health Officer for Brisbane. he went to Huchow. When he was four years of age he migrated to Brisbane. HENRY CHARLTON BASTIAN (1837-1915) Bastian was born at Truro in Cornwall. although he had a spell (as a patient) in a tuberculosis sanatorium at Saranac Lake. leprosy and filariasis. United States of America and graduated with a doctorate in medicine from Northwestern University in l906. He died suddenly from a myocardial infarction on 16 June 1894 aged 58 years. Between 1925 and 1928 he was appointed port physician for the Chinese Maritime Customs in Ningpo (= Ningbo). the son of Dr Joseph Bancroft and Ann Oldfield in 1860. He practised there until 1894 when he moved to Deception Bay 40 kilometres north of Brisbane where he managed a property inherited from his father that included a meatworks and experimental farm. Like his father. He received his . England on 26 April 1837. he had considerable time to devote to research. a post similar to that of medical superintendent. From 1911-1925 Barlow was located mostly in Shaohsing (= Shaoxing). China as a medical missionary for the Baptist Foreign Missions Society. he moved to the warmer climate of Queensland. Barlow remained with the Foundation for the next 21 years. While at Deception Bay. USA. In 1929 he joined the International Health Division of the Rockefeller Foundation and went to Egypt where he worked on the snail control of schistosomiasis. He was a keen horticulturist and was intrigued by the medicinal possibilities of Australian plants. He was a keen naturalist and was for three years president of the Nottingham Naturalists' Society. bachelor of medicine in 1863 and doctor of medicine in 1866. being a staunch advocate of heterogenesis (spontaneous generation). a post which he held until 1897. pharmacist second class (1864) and pharmacist first class (1869). It is uncertain when he died. His middle years were devoted to neurology but in his early and later years he was primarily concerned with the origin of life. at his own expense. Shortly after graduation he was elected assistant physician to St Mary's Hospital and lecturer in pathology at its Medical School. London graduating with the degree of master of arts in 1861. Julia (née Orane). becoming chief pharmacist in 1883. France. Buckinghamshire aged 78 years leaving his widow. He was elected a fellow of the Royal Society in 1868 when only 31 years of age for his contributions to parasitology. PAUL C BEAVER (1905-) Beaver was born in Indiana in the United States of America in 1905. He obtained the degrees of master of science and doctor of philosophy from the University of Illinois. He graduated in medicine in 1831 from the University of Louvain having first been apprenticed to Louis Stöffels. rising to the rank of professor of parasitology and director of the university's international centre for medical research in Cali. In 1875 he was appointed professor of botany and natural history in Toulon. Marguerite. In 1896 he was transferred to the Conseil Supérieur de Santé (high council of health). This latter story is a remarkable example of misguided moral courage and scientific enthusiasm in the face of hopeless odds.Biographies 787 education at University College. the son of François Bavay. Van Beneden made many contributions to the knowledge of the biology of parasitic worms. and Guadeloupe in the Caribbean (1869-1875). In 1843 he established. He died at home on 17 November 1915 at Chesham Bois. He served as editor of the "American Journal of Tropical Medicine and Hygiene" for twenty years. Colombia. a marine aquarium which was one of the first of its kind. New Caledonia in the South Pacific (1864-1869). (Plate 9) ARTHUR RÉNÉ JEAN BAPTISTE BAVAY (1840-?) Bavay was born on 29 April 1840 at Lamballe in Côtes de Nord. having published two monographs on free-living nematodes in which he described 100 new species and investigated their physiology. Louisiana in 1945. In 1835 he was appointed professor of zoology and comparative anatomy at the Catholic University of Louvain then became curator of the Natural History Museum in that city. He was also a physician to the National Hospital for the Paralysed and Epileptic from 1882-1912. In 1867 he was appointed professor of pathological anatomy then in 1887 professor of medicine and clinical medicine at University College Hospital. He remained there until he retired in 1902. three sons. and his wife. In 1877 he was made a Chevalier de la Légion d'Honneur (knight of the legion of honour). who inspired van Beneden to become a zoologist. serving in Brest and Lorient in France. He was much . In 1868 he married Anna Coz. (Plate 10) PIERRE JOSEPH van BENEDEN (1809-1894) PJ van Beneden was born on 19 December 1809 at Mechelen (Malines) in Belgium. a great collector of natural history specimens. a doctor. He studied pharmacy between 1858 and 1860 and was appointed in the French Navy as pharmacist third class (1860). and a daughter. In 1881 he was appointed professor of pharmacy and therapeutics in Brest. He joined the department of parasitology at Tulane University in New Orleans. then in 1845 transferred to Tübingen where he began the study of medicine. criminis literarii citatus". He remained there until 1937 when he retired to England. William Cowper in his Anatomy of Human Bodies published in 1698 in Oxford. he was an embryologist who discovered the phenomenon of meiosis. GODEFRIDUS GOVERT BIDLOO (1649-1713) Bidloo was born in Amsterdam. In 1843 he entered the University of Freiberg. Bilharz became . thus showing for the first time the true nature of this deadly disease. England on 23 November 1949 at the age of 76 years after a short illness. and being made a Grand Officer of the Order of Leopold in 1886. Edouard.788 A History of Human Helminthology esteemed for his high character and was the recipient of many honours. For a time he was physician to William of Orange. aged 84 years. He died at Carshalton. After two years as a resident at the Royal Southern Dispensary in Liverpool. After his graduation in 1849. His son. He was created a Companion of the Order of the Indian Empire (CIE) in 1929 and made a Commandant of the Order of the Nile in 1937. physician to the Viceroy of Egypt. In 1916 he married Gwendoline Harper by whom he had two sons and two daughters. first at the Hague and then at Leiden. He was the eldest of nine children and showed his taste for natural history as a youngster. In 1915 he was appointed director of public health in Bengal. These plates were plagiarized by the English anatomist and surgeon. and in 1692 became Inspector of Military Hospitals in England. In June 1850. an irate Bidloo wrote a scathing attack on the latter in a tract entitled "Guglielmus Cowper. Bidloo published an Atlas of Anatomy in Amsterdam in 1685 with 105 plates by the artist Gerard de Lairesse. (present-day West) Germany. but he showed that the recently-discovered Leishman-Donovan bodies were present in kala azar. he went to India for a number of years as chief medical officer for the Empire of India and Ceylon Tea Company in Assam. Two years later. In 1931 he left India for Egypt on being appointed professor of hygiene in the Egyptian University in Cairo. Bidloo died in Leiden. He studied first in Liverpool then in Edinburgh where he graduated with the degrees of bachelor of medicine and master of chirurgie in 1898. When Griesinger departed from Egypt in 1852. Bilharz returned to Freiberg where he was appointed prosector at the Anatomical Institute. there he was able to study the comparative anatomy of lower animals and to attend von Siebold's lectures on helminthology. amongst other things. In 1909 he undertook an extensive investigation of malaria in Bombay. THEODOR BILHARZ (1825-1862) Bilharz was born on 23 March 1825 at Sigmaringen on the Danube in Württemberg. Not only did he discover the cause of "ground-itch". collecting plants. He took a diploma in public health from Cambridge and a diploma in tropical medicine and hygiene in 1905. Holland in 1713. (Plate 11) CHARLES ALBERT BENTLEY (1873-1949) Bentley was born at Chipping Norton. insects and minerals. He studied medicine at the University of Leiden and eventually became professor of anatomy. England on 25 April 1873. Holland in 1649. Wilhelm Griesinger. a foreign corresponding member of the Royal Society of Britain. later King William III of England. he went to Egypt as an assistant to another former teacher. who had been appointed. The University of Calcutta conferred an honorary doctorate of medicine on him in 1931. including being elected president of the Royal Belgian Academy in 1881. The elder van Beneden died at Louvain on 8 January 1894. became professor of zoology at Liège in 1870. In 1922 he married Dr Mary Georgina Thompson. Bilharz contracted the disease himself. In 1921 he was created professor of the tropical diseases of Africa by the University of Liverpool and appointed first director of the Sir Alfred Lewis Jones Research Laboratory in Freetown. He was appointed associate professor of medicine at the Paris Faculty of Medicine in 1883. chief surgeon of the division for internal diseases. Bilharz attended a German lady who was living in that place and who was suffering from a febrile illness. was famous for devising the first parachute and for having been the first person to cross the English Channel in a balloon (1785).Biographies 789 successively chef-de clinique in the surgical division of Kasr-el-Aini Hospital. Scotland on 7 January 1879. Blanchard began the study of medicine and natural science at the University of Paris in 1875. Not only did he make major contributions to helminthology (schistosomiasis. died at the age of 26. He took the diploma in public health (London) in 1907. His father. In 1940 during World War II he was sent as a Surgeon-Captain in the Royal Navy Volunteer Reserve to Freetown. Bilharz remained unmarried. hookworm infection. Bilharz accompanied the Duchess of Saxe-CoburgGotha and her party to Massaua (also Massowah. (Plate 12) DONALD BREADALBANE BLACKLOCK (1879-1955) Blacklock was born at Oban in Argyllshire. Sierra Leone to control a malaria outbreak which was threatening shipping convoys. and on its inhabitants and their customs. now Mesewa) on the Red Sea in the Eritrean province of Ethiopia. In 1914 he was made director of the laboratory and was later appointed lecturer in parasitology. for example.) He retired to Cornwall and died at his home at Mawnan on 10 June 1955 at the age of 76 years. a presbyterian minister. He was educated at the University of Edinburgh where he graduated with the degrees of bachelor of medicine and bachelor of chirurgie in 1902. while the Duke and his companions went on an expedition to the interior. of which he became the secretary-general and moving spirit for twenty years. then in 1861 he moved to the department for syphilis and diseases of the skin. John Blacklock.G. variously recorded as being typhus and typhoid. In that same year he was appointed research assistant to the Liverpool School of Tropical Medicine's research laboratory and worked mostly on trypanosomiasis. they had no children. degree of doctor of medicine (Edinburgh) in 1909. During World War I he served in the Royal Army Medical Corps. In 1862. In 1929 he returned to Liverpool as professor of parasitology. the electric organ of the eel) and flora of Egypt. but his grand-uncle. the son of the Rev. was a modest man and painfully shy in the presence of strangers. a poet and author. then from 1934 until his retirement in 1945 he was professor of tropical hygiene. He and Milne-Edwards organized the first International Congress of . returned to Cairo and died there shortly afterwards on 9 May 1862 at the age of 37. While in Massaua. but was a valued friend to many. for these services he was made a Commander of the Order of St Michael and St George (C. In 1876. taeniasis nana). Sierra Leona where he remained for the next eight years. professor of medicine and professor of comparative anatomy (1856). Blanchard had helped found the Société Zoologique de France. heterophyiasis. (Plate 13) RAPHAEL ANATOLE BLANCHARD (1857-1919) Blanchard was born on 28 February 1857 at Sainte-Christophe (Indre-et-Loire) in France. and diploma in tropical medicine (Liverpool) in 1911. but he was also an authority on the fauna (describing. graduating as a doctor of medicine in 1882.M. Jean Pierre Blanchard. He practised for a few years in South Africa. the daughter of a wealthy landowner. then became the first president of the Société Française d'Histoire Médicale and helped found the Institut de Médecine Coloniale in 1902. He died suddenly on 7 February 1919 at the age of 62 years. publishing 603 books. He was the son of wealthy parents. He made major contributions to the understanding of insect biology and was the first person to describe the phenomenon of parthenogenesis when he showed that each female aphid produced 95 offspring without mating (1746). In 1806 he was appointed professor of veterinary medicine in Wilna (now Vilnius. USSR). as one biographer wrote. about natural science and philosophy. notes and articles. original papers. After travelling for a year studying natural science. and Blanchard was appointed president of the International Commission on Zoological Nomenclature in 1898. compelled him to give up making direct observations. In 1880 he was appointed a professor in comparative anatomy at the University of Dorpat (now Tartu in Estonia. France. becoming professor of anatomy there in 1816. now Alsace. A serious eye disease. In 1886 he moved to Rostock then in 1891 he was appointed professor of zoology and comparative anatomy and director of the zoological museum at the University of Königsberg (now Kaliningrad. his family having emigrated from France during the persecution of the Huguenots. which remained an essential zoological text for many years. "that he should have some enemies is natural for such is the fate of most leaders of men". As a young person he was hindered by increasing deafness. He died in Darmstadt on 2 April 1827 aged 50 years. In 1756 he married Jeanne-Marie de la Rive. Likewise he studied regeneration and showed that each section of Lumbriculus worms when cut into many pieces became perfectly reconstituted into an adult worm. he began medical practice in Darmstadt where he was admitted as a member of the College of Medicine in 1801. He graduated with the degree of doctor of medicine from Wurzburg in 1874 then three years later he was awarded a doctorate of philosophy. After a number of years of ill health he . (Plate 14) LUDWIG HEINRICH BOJANUS (1776-1827) Bojanus was born on 16 July 1776 at Buchsweiler in Elsass. Lithuania. Germany. brochures. and he spent the rest of his days engaged in theoretical speculations. In the previous year he had been appointed professor of medical zoology. He died at his estate near Geneva on 20 May 1793 at the age of 73 years. Switzerland on 13 March 1720. He had many warm friends but. He studied law and was elected to the council of his native city. His major work was a monograph on the anatomy of tortoises. He was a prolific author. He founded the Archives de Parasitologie in 1898. but he also had a lively interest in natural science and eventually devoted himself entirely to that pursuit. He studied medicine at Jena and graduated there in 1797. CHARLES BONNET (1720-1793) Bonnet was born in Geneva. He had a considerable command of languages and was an eloquent speaker. He was educated at the Universities of Greifswald and Würzburg where he studied zoology and medicine. a title which was changed in 1906 to parasitology. USSR) then in 1883 was made professor of zoology in that institution. MAXIMILIAN GUSTAV CHRISTIAN CARL BRAUN (1850-1930) Braun was born in Germany in 1850.790 A History of Human Helminthology Zoology. frequently with effusive religious overtones. Lithuania) where he remained until his retirement in 1922. however. an indefatigable researcher and a good organizer. He had the reputation of being one of the best breeders of sheep and cattle in the country.Biographies died on 19 February. Busk was appointed Assistant Surgeon to the Grampus. Apart from helminthology. His biographer has said that his modesty was such that he belittled his own achievements and he invariably gave more credit than was really due to his collaborators. the Seamen's Hospital ship at Greenwich. (USSR) where his father was a merchant in the English colony. paying particular attention to the Bryozoa and becoming interested in ethnology. He died in 1971. He was the first Home Office Inspector under the Cruelty to Animals (Vivisection) Act. He graduated with the degree of master of science from the National University of Ireland then went to the London School of Tropical Medicine in 1928. and in 1811 was appointed its curator. While in the West Indies between 1931 and 1933 he worked out the life cycle of Mansonella ozzardi. France in 1349. England. during which time he made important observations on cholera and scurvy. Austria. In 1815 he went to Paris in order to pursue studies in his field of interest. then graduated in 1830. He resigned his post as surgeon to the Dreadnought in 1855 and became Hunterian professor of anatomy and physiology at the Royal College of Surgeons between 1856 and 1859. Bremser published papers on a number of infectious diseases including scarlet fever. He studied onchocerciasis in Kenya in 1938 and in the 1950s undertook a number of experiments with Brugia. In 1832. He studied zoology at Jena and graduated in 1792. the acting director of the National Museum of Ireland. Ireland in 1904. He married his cousin Ellen in 1843 and had two daughters. JEAN de BRIE (1349-?) Jean de Brie was born at Villiers-sur-Rougnons. He served in this capacity for 25 years. He died in Vienna on 21 August 1827. He was commissioned by King Charles V of France to write a book on the proper management of sheep and the best means of wool production. Busk turned his attention to more general aspects of biology. then was apprenticed for six years to George Beaman. a post which he held with tact and impartiality. malayi and concluding that he had developed tropical eosinophilia. and in it de Brie described the liver fluke. and afterwards to the Dreadnought which replaced it. cowpox and measles. the son of J J Buckley. He was educated at Dr Hartley's school in Yorkshire. aged 80 years. GEORGE BUSK (1807-1886) Busk was born on 12 August 1807 in St Petersburgh (Leningrad). Russia. aged 60 years. This was completed in 1379. being articled at the Royal College of Surgeons. He then undertook further studies in medicine in Vienna. In 1806 he became associated with the museum of natural history in Vienna. near Coulommiers. (Plate 15) 791 JOHANN GOTTFRIED BREMSER (1767-1827) Bremser was born on 19 August 1767 at Wertheim. He was elected a fellow of the Royal Society in 1850. A biographer wrote that "Busk was full of knowledge. inoculating himself on three occasions with B. . JOHN JOSEPH CRONIN BUCKLEY (1904-1971) Buckley was born in Dublin. In 1963 he developed a lower limb paresis associated with intolerable pain. (present-day West) Germany. He spent some time at St Thomas's Hospital. military arts. In 1815 he sailed around the world as naturalist with the Russian. is extant. In 1812 he went back to Berlin to study medicine and science. (Plate 17) ADELBERT von CHAMISSO (1781-1838) Von Chamisso (also known as Charles Adélaïde Chamisso) was born. Von Chamisso was elected a member of the Academy of Science in 1835 and died in Berlin on 21 August 1838 aged 57 years. without a trace of vanity. at Schloss Boncourt in the Champagne district of France on 30 January 1781. He returned to England in 1904. AULUS CORNELIUS CELSUS (30 BC-50 AD) Celsus lived during the reign of Tiberius Caesar at the height of Roman civilization immediately after the founding of the Empire. India on 7 May 1908 aged 29 years. . He was educated at Queen's College in Cork. He studied medicine at the University of Aberdeen and graduated with the degrees of bachelor of medicine and bachelor of chirurgie in 1900 and he later obtained a diploma in public health from the University of London. honest gentleman". nobleman and medical historian. Manipur State. Subsequently he became professor of surgery in Calcutta. De medicina. In 1820 he married Antonie Piaste by whom he had seven children. a devoted friend. then joined the Indian Medical Service as a lieutenant on 1 September 1905. philosophy and jurisprudence. He was a landowner. He died of cholera at Imphal. His interests lay in the realms of writing lyrics and in natural science. In 1798 he entered military school in Berlin and was commissioned in the Prussian Army as a lieutenant in 1801. He wrote an encyclopaedia. and cautious in the conclusions he drew from his observations. and an upright. Following the surrender of his regiment in 1806. (Plate 16) JOHN CATTO (1878-1908) Catto was born in August 1878 in Britain. He was knighted in 1912. which contained sections on agriculture. Ireland then entered the Indian Medical Service in 1882. Captain Otto von Kotzebue on the brig Rurik.792 A History of Human Helminthology an unwearying collector of facts. He was said to have a forceful personality but was a good friend to all who gained his confidence. He was soon appointed to the Afghan Boundary Commission then at an early age was made professor of anatomy and surgery at the Lahore Medical College. a devoted labourer in the paths of science. He was a man of unaffected simplicity and gentleness of character. it was re-discovered in 1443 when a copy of the manuscript was found in the papal library in Milan. then became curator in 1833. While employed as a resident medical officer in Singapore. He was probably a scholar with limited clinical experience. Only the last section. RICHARD HAVELOCK CHARLES (1858-1934) Charles was born in 1858. In 1819 he was appointed adjunct curator of the Royal Botanical Gardens in Berlin. He died at his home in Harley Street. but he held most of the contemporary knowledge of medicine within his grasp. the son of a count. London on 10 August 1886. following which he wrote a book on his experiences and observations. "De artibus". he obtained the specimen in which he eventually found Schistosoma japonicum adult worms. aged 79 years. rhetoric. He reached the rank of Major-General in the Indian Medical Service and was appointed medical adviser to the Indian Office. he returned to France. more particularly to the internal parasites of man which was published in 1864. Near the end of that year.B. He went to Cambridge University then continued his medical studies at St. the son of Richard Cobbold. At the age of 16. London. Bartholomew's Hospital.Biographies 793 After several years of failing health he died on 27 October 1934. following the success of his book. then two years later became Director of Medical Services to the Sudan Government. first at St. Meanwhile. (Plate 19) THOMAS SPENCER COBBOLD (1828-1886) Cobbold was born on 28 May 1828 at Ipswich.E. In 1856 he went to London and was appointed lecturer in botany. After a short period in Paris. then was appointed professor of geology at the British Museum in 1868 and professor of botany and helminthology at the Royal Veterinary College in . considerate soul with a keen. On his release shortly afterwards. began a consultative practice in helminthology. Yorkshire. he turned his attention to respiratory diseases and became a member of the staff of the London Chest Hospital. zoology and comparative anatomy. the son of a clergyman. In the same year he was elected a fellow of the Royal Society. England on 30 April 1868. He died at his home in Lydney-on-Severn in Gloucestershire. In 1916 during World War I he went with a Red Cross unit to Serbia (now part of Yugoslavia) but was taken prisoner-of-war by the Austrians. Cobbold did not practise medicine for many years but in 1865. he took the membership of the Royal College of Physicians in 1905 and was elected a fellow of that College in 1913. In 1909 he resigned these appointments to become Director of the Civil Hospitals in Khartoum and Omdurman. Mary's Hospital and then (1861) at the Middlesex Hospital Medical School. He was described as being a kind. England. a well-to-do clergyman. gained the fellowship of the Royal College of Surgeons in 1897 and proceeded to the degree of doctor of medicine from Cambridge in the following year. inquisitive look and an enquiring mind. his wife having pre-deceased him by several years. In 1902 he was appointed physician to the Governor-General of the Sudan. serving as the secretary to the War Office Commission on Medical Establishments in the British Expeditionary Force. In 1852 he married a Miss Amyss of Suffolk by whom he eventually had several daughters and a son. but then went to South Africa as surgeon to the Imperial Yeomanry Hospital during the Boer War. his main clinical interests had evolved from surgery to medicine. Although he did not lose interest in tropical medicine. He settled in London after the war and was honoured by being made a Commander of the Order of British Empire (C. a surgeon in Norwich. England on 21 July 1955 at the age of 87 years. he took several resident positions in that hospital. Suffolk. he became apprenticed to J G Crosse. for three years then in 1847 he went to Edinburgh to study medicine and graduated with the degree of doctor of medicine in 1851. After graduating in 1893. He wrote the first major English textbook on parasitic diseases: Entozoa: an introduction to the study of helminthology. he returned to the Sudan where he was to make his observations on the efficacy of antimony in the treatment of schistosomiasis. he went to France. (Plate 18) JOHN BRIAN CHRISTOPHERSON (1868-1955) Christopherson was born at Bakley. Between 1896 and 1902 he was on the surgical staff of the Albert Dock Hospital. he became curator of the Anatomical Museum of the University in Edinburgh and remained there for several years while working on comparative anatomy. In 1912 he married Joyce Ormerod. a daughter of one of the physicians at St Bartholomew's Hospital.) in 1919. In 1894 he was transferred to British Guiana (now Guyana). he entered the Colonial Medical Service in 1889 and was sent to Fiji. He received his doctorate in 1837 for a thesis on haematocoele in the tunica vaginalis. 14 years before Metchnikoff. Maria Forbes. All this research was carried out while Davaine practised medicine for he never had a laboratory of his own. aged 65 years. was devoted to music. On his return to London he was made superintendent of the London School of Tropical Medicine but two years later he was sent to Malaya (Malaysia) to direct the new Institute of Medical Research in Kuala Lumpur. Davaine described the causative organism of anthrax and was the first to recognize the pathogenic role of bacteria. . and possessed a remarkable alto voice. spending his clinical years at the Paris Hospital. Outside of medicine. he was appointed physician to the French Emperor. He was said to be of a kind and affectionate disposition (although his often dogmatic writings at times appear to belie this). In 1869. Cambridge and at the London Hospital. In 1905 he retired from the Colonial Service and returned to the London School of Tropical Medicine as Director. (Plate 21) CASIMIR JOSEPH DAVAINE (1812-1882) Davaine was born on 19 March 1812 at Saint-Amand-les-Eaux in France. After three years in various posts in the London Hospital. In 1912 he was appointed adviser to the Colonial Office where he remained until 1920 when ill health forced him to retire. He was surgeon to the Maison Municipale de Santé and a member of the Academy of Medicine in Paris. In 1869 he married an Englishwoman. the son of a farmer. He was elected a member of the Société de Biologie in 1848 and became its treasurer and archivist. the sixth child of Benjamin Joseph Davaine. (Plate 20) CHARLES WILBERFORCE DANIELS (1862-1927) Daniels was born on 9 May 1862. He entered the Collège of Tournai in 1828 then moved to Lille. Thomas Daniels. by whom he had a son. nor did he hold an official university position. He began the practice of medicine in Paris but developed an interest in natural history. He never married. Because of his fame. he described phagocytosis by human leucocytes. aged 70 years. In 1830 he went to Paris to study medicine. a small village in the department of Somme. He died in Garches from an abdominal malignancy on 14 October 1882. He died from cardiac disease in London on 20 March 1886 at the age of 57 years. He was educated at Trinity College. made and kept many friends. he published a paper on lice in 1839. a distiller. England.794 A History of Human Helminthology 1872. for example. Demarquay never married. especially parasitology. He graduated in medicine and specialized in surgery becoming a famous exponent of the art. graduating from the University of Cambridge with the degree of bachelor of medicine in 1886. The first edition of his great textbook of parasitology appeared in 1860 and the second edition was published in 1877. A progressive and disabling illness dogged his last years in Ilford until his death on 6 August 1927. In 1899 he went to Calcutta on behalf of the Royal Society to study Ross's work on the transmission of malaria then later that year he proceeded to Nyasaland (Malawi) as a member of the Royal Society's Commission on blackwater fever. he was a rose-fancier. France in 1814. the third son of the Rev. (Plate 22) JEAN NICHOLAS DEMARQUAY (1814-1875) Demarquay was born in Longueval. In 1844 he wrote a work on the development of the fetal human brain between the ages 5 weeks and 7 months. rector of Hulme near Manchester. He was a man of literary pursuits and possessed a very extensive library. During the first World War he joined the French Army Medical Service. then in 1840 was appointed an assistant in the Medical Clinic of the University of Pavia. In 1924 he was appointed professor of clinical medicine in Rouen. He studied medicine at the University of Pavia and received his degree in 1837. In 1865. In 1923 he was jointly appointed to the surgical staff of the Royal Melbourne Hospital and made assistant director of the adjacent Walter and Eliza Hall Institute of Medical Research. He wrote three books and more than 300 articles on hydatid disease. He returned to Milan and was appointed as an assistant at the Ospedale Maggiore. Lima and Buenos Aires and was an honorary professor of the Faculty of Medicine in Montevideo. He died on 17 November 1962. Vienna and Heidelberg in order to study French. (Plate 25) . He wrote his classic monograph on echinococcosis in 1928 then two years later he was appointed to the Royal Prince Alfred Hospital as the first full-time professor of surgery in Australia by the University of Sydney. and in 1849 was appointed a member of a commission for the study of rabies. London. He received much recognition for his work. he wrote a cookbook which received popular acclaim. English and German. In 1902 he went to Rouen and entered clinical practice. Because of his contributions. Italy on 8 December 1813. during which time he discovered hookworm. and while there in 1900 began his long series of investigations on echinococcosis. and retired in 1956. He studied medicine at Paris. He spent the next two years at the Milan Hospital (Ospedale Maggiore). (Plate 24) ANGELO DUBINI (1813-1902) Dubini was born. aged 60 years. he became chief physician and head of the department of dermatology in the same hospital and remained there until his retirement in 1878. In 1841 he travelled to Paris. FÉLIX DÉVÉ (1872-1951) Dévé was born at Beauvais. In 1920 he took the fellowship of the Royal College of Surgeons. of cancer of the stomach on 21 June 1875. In his retirement. (Plate 23) HAROLD ROBERT DEW (1891-1962) Dew was born in Melbourne. He took his microscope with him on his travels and expanded his interest in pathology. Australia on 14 April 1891. Uruguay. He became president of the Royal Australasian College of Surgeons in 1954-55. and another work on the keeping of bees. died a millionaire.Biographies 795 and although born of poor parents. aged 88 years. he was made a Commandant of the Legion of Honour. he was promoted to become head of the pathological services in the hospital. in Milan. In 1847. He immediately joined the Royal Army Medical Corps and served in Palestine and France. He fractured a femur and died in that place on 28 March 1902. having left Paris two weeks earlier. He died suddenly in Paris on 1 September 1951 aged 78 years. he was a member of the Academy of Medicine in Paris and corresponding member for the academies in Rome. He died in Longueval. He invented many surgical devices and published papers on surgery. aged 71 years. France on 10 November 1872. He studied medicine at the University of Melbourne and graduated in 1914. of a poor family. was knighted in 1955. He spent the last few years of his life at Cassano Magnago where he indulged these hobbies. pharmacology and hypnosis. dysentery and typhus. Queensland where he proved that mepacrine was a valuable prophylactic for malaria. In 1823 he had married Clémentine Gregoire. one of whom became a well-known oncologist before he was killed by a terrorist bomb in London. Missouri in the United States of America on 7 September 1890. He proved that sponges were animals and first observed the motility of leucocytes. he joined the Army and was posted to Egypt with the Australian Expeditionary Force. NEIL HAMILTON FAIRLEY (1891-1966) Fairley was born in Melbourne. He obtained a bachelor of arts degree from Oberlin College. In 1839 he was appointed professor of geology in Toulouse but in the following year he was called to the chair of zoology and botany at Rennes. He returned to Australia but in 1921 was appointed professor of tropical medicine in Bombay where he researched on tropical sprue. having been persecuted by his colleagues. He graduated in medicine from the University of Ghent in 1901 then studied at the Liverpool School of Tropical Medicine in England. He made a number of contributions to parasitology. Almost immediately. but illness forced him to retire in 1948.796 A History of Human Helminthology FÉLIX DUJARDIN (1801-1860) Dujardin was born at Tours in France on 5 April 1801. the most notable being his book. Belgium in 1877. He spent the last few years of his life almost as a recluse. Australia in 1891 and graduated in medicine from the University of Melbourne in 1915. He did not turn his attention to zoology until he was over 30 years of age. He was awarded a master of arts degree in 1914 and obtained the doctorate of philosophy in 1917. During World War II he was commissioned a brigadier in the Australian Army and was appointed director of the Land Headquarters Medical Research Unit at Cairns. Hamburg. He was appointed a professor of legal medicine in 1910 and professor of medicine in 1919. Histoire naturelle des helminthes ou vers intestinaux. He retired in 1934. cerebrospinal fever. PAUL VAN DURME (1877-1947) Van Durme was born in Ghent. then professor of geometry then of chemistry at the University of Tours from 1826. He visited the centres of tropical medicine in London. He was a versatile and gifted person who applied his talents to a number of vocations. In 1924 he returned to the Walter and Eliza Hall Institute of Medical Research in Melbourne and worked on snake bite. He served as an instructor in the same institution for the next two years then went to the Peking Union . he remained there until his death. He died in Sonning. Ohio in 1912 then went to the University of Illinois to study parasitology. the son of a watchmaker. England on 19 April l966 leaving a widow and three sons. he made important contributions in a number of areas. bookseller. He was knighted in 1950. He improved the performance of the microscope by developing a system of lenses beneath the stage which became the fore-runner of the modern condensor. (Plate 26) ERNEST CARROLL FAUST (1890-1978) Faust was born in Carthage. Marseilles and Paris. dying 13 years later in 1947. In 1928 he went to London as physician to the Hospital for Tropical Diseases. While in the Middle East he made original observations on schistosomiasis. Being a person of catholic and wide-ranging interests. He died in Rennes on 8 April aged 59. After the war he was appointed to the chair of clinical tropical medicine in the University of London. becoming an engineer. flora and fauna of the region was published posthumously between 1873 and 1876 as Fedchenko's Journeys in Turkestan. Samarkand and Tashkent in south central USSR. In 1918 he was awarded the prize of the Imperial Academy of Japan for his researches in schistosomiasis. He was said to be a man of fine character and delightful personality and was admired by his students and colleagues. In 1928 he returned to the United States as professor of parasitology at Tulane University in New Orleans. in Turkestan. (Plate 27) WINTHROP DAVENPORT FOSTER (1880-1918) Foster was born in the United States of America in 1880. He remained there until 1928. He married Lola Swift by whom he had one daughter. then spent the next four years studying pathology in Germany. He was a voluntary assistant in anatomy with Virchow and studied anthropology. He died on 18 November 1934. in an accident while climbing Mont Blanc. In 1947 he was appointed professor of tropical diseases and hygiene in that institution. his mother sold the estate and moved to Moscow to facilitate the family's education. He is perhaps best remembered for his text on helminthology which became incorporated into Craig and Faust's Clinical Parasitology. On 15 September 1873 he was killed. During this period he studied the . (Plate 28) FRIEDRICH FÜLLEBORN (1866-1933) Fülleborn was born on 13 September 1866 at Kulmbach in (present day West) Germany. he is buried in the English cemetery at Samoëns. Following graduation. aged 88 years. he taught at Moscow University then in 1866 became assistant dean of the student body. He married a fellow student. He died in 1918. still the bible of medical parasitology.Biographies 797 Medical College in China in 1919. He visited Cobbold in London in 1873 then went to the French Alps. He was the first explorer of Central Asia and his work on the geology. Uganda). He studied for a short period with Leuckart then between 1868 and 1871 sojourned with his wife. In 1899 he was appointed professor of pathology at the Imperial University of Tokyo and held this position until his retirement in 1930. He died in New Orleans on 2 November 1978. aged 29 years. ALEKSEJ PAWLOWICH FEDCHENKO (FEDTSCHENKO) (1844-1873) Fedchenko was born on 7 February 1844 at Irkutsk near Lake Baikal in Russia (USSR). United States Department of Agriculture. then travelled to Scandinavia where he collected insects and worked on the measurement of Finnish skulls. He studied medicine at Berlin University. He worked as a zoologist at the Bureau of Animal Industry. rising to the rank of associate professor of parasitology. During this period he wrote classic monographs on clonorchiasis and schistosomiasis japonica. Between 1896 and 1900 he was a medical officer in the German Colonial Army in German East Africa (now Tanzania. The Fedchenko glacier in Turkestan is named after him. In 1894 he went to North America to study the embryology of certain fishes on behalf of the Royal Prussian Academy of Science. OA Armfeld. Louisiana. He graduated from the Faculty of Medicine of the Tokyo Imperial University in 1895. After the death of his father. AKIRA FUJINAMI (1870-1934) Akira Fujinami (also known as Kan Fujinami) was born in the Aichi prefecture of Japan in 1870. His great work on parasitic worms was submitted to the Academy of Science in Copenhagen in response to its call for communications on the origins of intestinal . Germany. being appointed surgeon. (East) Germany on 28 May 1731. He wrote on many subjects but his masterpiece was his immense four volume Historia animalium in which the animal world was arranged according to the principles of Aristotle. This was to lead to books on the Nyasa tribes and the people of Tanganyika (Tanzania). JOHANN AUGUST EPHRAIM GOEZE (1731-1793) Goeze was born in Ascherleben. He was a prolific writer on medicine. architect and mathematician. Subsequently. amongst other things for the gladiators at their summer games. In 1920 he undertook research in the West Indies and South America while later travels carried him to East Africa. the son of Nicon. then was appointed the first town-physician of Zurich. His father was a protestant artisan who fell at the battle of Kappel in 1531 in which the civic guard of Zurich under Zwingli were defeated by the Catholics. that he was quoted endlessly and with finality for the next 1400 years until the dawn of modern clinical investigation. then studied in succession in Smyrna. Eventually. an institution for medical teaching and healing.798 A History of Human Helminthology fauna and ethnology of the Nyasa and Kinga mountains. He became a hospital chaplain in 1755. Corinth and Alexandria. he became more interested in anatomy. his friends sent him to study at their expense in Basle. Galen was taught in the local temple of Aesculapius. On the outbreak of World War I he was called up for military service and shortly afterwards was severely wounded at Mons in France. Goeze acquired a microscope and made major contributions to the knowledge of natural history. a fine cook and a persistent smoker. Switzerland on 26 March 1516. aged 48 years. Thereafter he was appointed an expert on malaria and hygiene to the German troops operating in Macedonia. Subsequently. a landowner. In 1930 he was appointed director of the Hamburg Institute and professor in the University of Hamburg. In 1901 he joined the newly-formed Institute for Naval and Tropical Diseases in Hamburg. particularly in the fields of entomology and helminthology. (Plate 30) KONRAD GESNER (1516-1565) Gesner was born in Zurich. where he read many subjects including classical and oriental languages. India and Japan. of the plague that ravaged Zurich in that year. (Plate 29) GALEN (129-c. mathematics and grammar. He died on 13 March 1565. experimental physiology and general medicine. He was professor of Greek at the Lausanne Academy from 1537-1540. He studied theology in Halle between 1747 and 1951 and was a preacher in Quedlinburg (East Germany).200 AD) Galen was born in 129 AD at Pergamum in Turkey. He returned to Pergamum and began the practice of medicine. he was summoned to Rome by the emperor to become his personal physician. Blas in Quedlinberg. In 1786 he was made dean of the cathedral in that city. He married relatively late in life and died on 9 September 1933. Such was his authority. philosophy. He had a quiet nature and a constant struggle with financial difficulties but his energy was marvellous. Paris and Montpellier. In 1908-9 he led an expedition to the South Pacific to make anthropological observations. Fülleborn was a great raconteur and linguist. then in 1762 he was appointed minister to the protestant church of St. aged 66 years. natural science and medicine. replaced Clot Bey and other French administrators and teachers with persons of German nationality. a political change of great importance occurred in Egypt. Grassi has been eulogised as an "indefatigable (who) showed great enthusiasm and perseverance in his work and granted first-hand importance to originality. He and Ronald Ross had a great controversy over which of them first discovered that malaria was transmitted by Anopheles mosquitoes. In 1849 he was appointed professor of pathology and therapeutics at the University of Kiel. he turned to research rather than clinical practice. He died in Quedlinberg on 27 June 1793 aged 62 years. In 1883 Grassi returned to Italy and was appointed professor of zoology. In 1845 he published a major textbook Die Pathologie und Therapie der psychischen Krankeiten (Pathology and treatment of psychiatric illness). He died in Rome on 4 May 1925 aged 71 years and was buried in the small village of Fiumicino where he had conducted a malaria control campaign for the last seven years of his life. he became a major force in psychiatry. While still a medical student in 1878. comparative anatomy and physiology at the University of Catania. Mehemed Ali. Following his graduation. At this time. It was in Germany that he met his future wife. In 1847 he was appointed lecturer in pathology. his time there was not altogether a happy one and he returned to Germany in 1852. In 1843 he returned to Tübingen. (Plate 31) WILHELM GRIESINGER (1817-1868) Griesinger was born on 29 July 1817 in Stuttgart. the anatomist. He began a practice at Friedrichschafen at Bodensee (Lake Constance) in 1839 then a number of appointments in Paris. and personal physician to the Viceroy was offered to Griesinger who went to Cairo in 1850. GIOVANNI BATTISTA GRASSI (1854-1925) Grassi was born on 27 March 1854 in the small Italian town of Rovellasca in Lombardy. Gegenbauer. (Plate 32) . then devoted the last three years of his life to full-time psychiatric practice. He began his medical studies at Tübingen University in 1834 but. He was professor of medicine in Zurich from 1860-1864. (present day West) Germany. Winnenthal (where he received his psychiatric training). Maria Koenen. Butschli. especially in the linking of that discipline to physiology and internal medicine. He died on 26 October 1868 aged 51 years. and Stuttgart followed. zeal and exactness" by some. then the zoologist. In 1880 Grassi won a scholarship to the University of Messina to study zoology. but damned as a plagiarist. Abbas. liar and fraud by others. The triple post of Director of the Medical School. In 1872 he entered the Faculty of Medicine at the University of Pavia to both learn the practice of medicine and to embark upon a career in research. In 1908 Grassi was appointed a Senator of the Kingdom of Italy for life. because he was a member of a banned student organization. he went to Heidelberg and Würzburg in Germany to study under first. Subsequently. President of the Sanitary Council. the francophile Viceroy. Although he made major contributions to the knowledge of hookworm disease and schistosomiasis. had to move to Zurich in 1837 to complete his training. In 1895 he moved to the same chair in Rome. died and his successor. Subsequently. truthfulness. he found that hookworm infection could be diagnosed by finding eggs in the faeces.Biographies 799 worms and received second prize (silver medal). materia medica and the history of medicine in Tübingen. which was to have a seminal role in neuropsychiatry. He also served on the staff of the London Fever Hospital. he was interested in botany and geology. . He died in 1893. In 1851 he published his treatise on embryology. where he graduated with a bachelor of arts in 1597. He travelled through France. he was also a successful practitioner and was appointed physician to King James I and his son Charles I. WILLIAM HARVEY (1578-1657) Harvey was born at Folkestone in Kent. Even though he was one of the greatest physiologists of all time. He studied letters. He was elected an assistant physician to King's College Hospital in 1863 and held this post until he was appointed to the same position at St. the son of a yeoman farmer.800 A History of Human Helminthology JOHN HARLEY (1833-1921) Harley was born in Shropshire. He was promoted to full physician at the latter institution in 1879 and was created consultant physician in 1893. He received his medical education from King's College. He made many contributions to comparative medicine and wrote a history of anatomy. "Exercitatio anatomica de motu cordis et sanguinis in animalibus" (Study on the motion of the heart and blood in animals). In 1685 he was elected to the Academia Naturae Curiosorum under the pseudonym of Aristotle II. England in 1833. Exercitationes de generatione animalium (Studies on the generation of animals). He then returned to England and received the degree of doctor of medicine from the University of Cambridge. In 1607 he was admitted to the College of Physicians then in 1609 he was appointed to the staff of St Bartholomew's Hospital in London. aged 79 years. London and qualified in 1858. He received a doctorate of medicine from the University of London and was elected a fellow of the Royal College of Physicians in 1867. He died in Königsberg in 1707. Outside of medicine. he described the circulation of the blood. He expounded views on the origins of certain diseases that were entirely unwarranted by contemporary discoveries in pathology and bacteriology with the result that he lost the respect of his professional colleagues. He died in Sussex on 9 December 1921. successively. In 1604 he married Elizabeth Browne but had no children. Thomas's Hospital. He was educated at King's School in Canterbury then entered Caius College. professor of history and of medicine. (Plate 33) ERNST FRIEDRICH GUSTAV HERBST (1803-1893) Herbst was born in Göttingen in present-day West Germany in 1803. He was educated at the University of Göttingen and spent most of his professional life in that city. England on 1 April 1578. He then travelled through France and Germany to Padua. theology and medicine in Königsberg. He died near London on 3 June 1657. probably from a stroke. USSR) from 1669 and received his degree in the last subject in 1678. Cambridge. Italy where he received a doctorate in arts and medicine in 1602. He returned to Königsberg and was appointed. Holland and England in order to further his knowledge. this work was not published until 1628. bowing and shaking hands on every possible occasion with every acquaintance that he met became an easily caricatured joke. In his Lumleian Lecture of April 1616. East Prussia (now Kaliningrad. Prussia (now East Germany) in 1648. PHILIPP JACOB HARTMANN (1648-1707) Hartmann was born in Stralsund in Pomerania. His habit of smiling. (Plate 35) ISAO IJIMA (1861-1921) Ijima was born in Hamamatsu. but Russian domination was so oppressive to him that he went to Leipzig in 1894. He then moved to Freiburg. He spent several years in Germany and received the degree of doctor of medicine from the University of Freiburg in 1901. The oath. Following working in Grassi's laboratory in Italy for five years. Subsequently. On the articulations. he became director of the Seamen's Institute in Kobe and director of the Japanese Hospital for Tropical Diseases. the son of a famous engineer. and The law. Hippocrates' lectures were said to be given under a plane tree in a village on the island of Cos. He studied at Ishikawa Prefecture School of Medicine and was licensed in 1887. A marble bust of Hippocrates was found in 1940 near the ruins of Ostia Antica. He published an Outline of Zoology in 1918 and is generally considered to be the father of Japanese parasitology. he went back to Basel as privatdocent in 1911. (Plate 36) CONSTANTIN JANICKI (1876-1932) Janicki was born in Moscow. (Plate 37) FUJIRO KATSURADA (1867-1946) Katsurada was born in Japan in 1867. On airs. In 1919 he returned to Warsaw to take up the post of professor of zoology. In 1908 he received the degree of doctor of medicine. He went to Germany for post-graduate studies. He was awarded the degree of doctor of science in 1892. the son and grandson of physicians. waters and places. On fractures. "The genuine works of Hippocrates". and Germany. He made many contributions to ornithology and the study of sponges. contains Prognostics. the son of a samurai. He was appointed professor of medicine at Okayama Medical College in 1903 and remained there until 1914. He was accorded honorary Athenian citizenship and is believed to have died in Thessaly. On wounds of the head. Russia (USSR) in 1876. He studied zoology at the University of Tokyo and graduated in 1882. He then continued his education at the Faculty of Medicine of the Tokyo Imperial University. (Plate 38) KENJI KAWANISHI (1868-1927) Kawanashi (also known as Kasai) was born in Japan in 1868. Switzerland where he received his doctorate in 1906. Germany and finally to Basel. Here he fell under the influence of Leuckart and studied there for four years. First and third books of epidemics. Manchuria.460-375 BC) Hippocrates was born on the Greek island of Cos. Regimen on acute diseases. and was himself to be given the accolade of "Father of Physic". then returned to his own university where he became professor of zoology and director of the Marine Experimental Station at Misaki. He remained in the army as a medical officer and was stationed in Taiwan. Poland. the seaport of imperial Rome. Adams's translation. Shizouka prefecture in Japan in 1861. He began the study of medicine at the Tokyo Imperial University but in 1889 was drafted into military service during the Sino-Japanese War.Biographies 801 HIPPOCRATES (c. He committed suicide in 1932. He began his studies at the University of Warsaw. He rejected mysticism and emphasized the role of clinical observation in the study of disease. Kanawaga prefecture. Aphorisms. He then resumed his medical studies at Kyoto Imperial University. A large number of writings have appeared under his name but they probably represent the labours of many. He . He became a lecturer at the University of Amsterdam and chief curator of the Aquarium. All of his experiments were done at his own behest and without the benefits and facilities of a university environment. then in 1925 he was made professor of parasitology at the Cairo Medical School. COENRAAD KERBERT (1849-1927) Kerbert was a student in Amsterdam. Initially. then spent between 1920 and 1922 at the London School of Tropical Medicine. then later in Prague. Egypt on 23 May 1915. trichostrongyliasis and malaria. In 1922 he was appointed sub-director for parasitic diseases at the Public Health Laboratories in Cairo. GOTTLOB FRIEDRICH HEINRICH KÜCHENMEISTER (1821-1890) Friedrich Küchenmeister was born on 22 January 1821 in Buchheim near Lausigk in Saxony. he was destined for the ministry and began the study of theology. paragonimiasis. (present day West) Germany. He died in 1969. He investigated plague then returned to the department of parasitology of the Keio University Medical School in Tokyo. perhaps the best . (Plate 39) HARUJIRO KOBAYASHI (1884-1969) After graduating from the Kyoto Imperial University in Japan. He published several books on parasitology. In 1927 he joined the department of paediatrics in Keio University Hospital. Japan. In 1876 he wrote a dissertation on reptile skin. He died in 1971. here he was given the title of "medicinalrat" or medical councillor. Kobayashi studied schistosomiasis japonica at the University of Tokyo. Holland then undertook post-graduate studies with Rudolf Leuckart in Leipzig in present-day East Germany. He was a dynamic man of catholic interests. He was appointed as a clinical assistant at the Kasr-el-Aini Hospital in Cairo in that year. then was appointed the first director of the South Manchurian Medical School. including an account of the parasites of Korea. MOHAMED KHALIL (1895-?) Khalil was born in Cairo. He began private practice in pediatrics in 1929. but then changed to medicine which he studied first in Leipzig. Parasitology was never the same after his demonstrations of the importance of experimentation. In 1859 he moved to Dresden (East Germany) where he continued both his medical practice and his research. His experiences led him to write his famous textbook of parasitology. Awagun in Chiba Province near Tokyo. (Plate 40) SHIMESU KOINO (1897-1971) Koino was born in 1897 at Tomiyama-cho. He studied medicine at the University of Manchuria. He introduced the operation of ovariotomy to Germany and displayed considerable ingenuity in inventing and modifying surgical instruments.802 A History of Human Helminthology became head physician of the South Manchurian Railway Hospital in Dairen. the son of a protestant pastor. In 1846 he began the practice of medicine in Zittau (East Germany) and became particularly expert in the fields of obstetrics and gynaecology. In 1890 he succeeded CF Westerman (after whom he had named Distoma westermanni) as director of the Royal Zoological Society. In 1916 he went to Korea where he made a number of original investigations on clonorchiasis. then in the next year was appointed as an assistant at the Zoology Laboratory in Amsterdam. He studied medicine at the Government Medical School in Cairo and graduated in 1918. graduating in 1920. (Plate 43) ANTONY van LEEUWENHOEK (1632-1723) Van Leeuwenhoek was born in Delft. and the frequency of consumption in Saxony. a prosperous basket-maker. was much loved and respected. he returned to his native town and began work as a . Spain. His study was said to be littered with theological texts and he was a masterly exponent of the scriptures. When he was 22 years old. He was one of the first advocates of the official inspection of meat and meat markets. He investigated the propagation and treatment of cholera. London between 1834 and 1837. as a doctor. the son of Philips Thoniszoon. a post which he held until his death.Biographies 803 known of these was an apparatus for plugging the nostrils in epistaxis. As a boy he was sent to Amsterdam to receive a business training while he worked in the cloth trade. Antony took his surname (Lion's corner) from the house near the Leeuwenpoort (Lion's gate) at Delft owned by his father. the son of a doctor. translated Küchenmeister's two volume text Animal Parasites from the German. his History of Physick being published in 1696. In 1862 he was appointed coroner for Central Middlesex. (Plate 42) EDWIN LANKESTER (1814-1874) Lankester was born on 23 April 1814 at Melton. He popularized the treatment of diphtheria with lime water. in Suffolk. He died in London on 2 January 1948. in Dresden in 1874 he began the practice of the placement of ashes in urns. but underneath he was said to have a heart of gold and. rising to the rank of lieutenant-colonel. He became a councillor of state in 1702 and held this position until his death in 1728. London. He returned to Geneva and began to practise. He studied in Montpellier and in Paris. George's Hospital Medical School in 1843 and was elected a fellow of the Royal Society in 1845. and was an avid bee-keeper. he was cremated at Gotha in the crematorium of which he was a founder. but his great interest was in medical history. Mary's Hospital in London. England. In 1850 he was made professor of natural history at New College. and in an appendix to that work named the fluke now called Fasciolopsis buski. For some years he edited a journal of his own entitled Periodical of Epidemiology. England and graduated with the degree of bachelor of medicine in 1893. He died in Dresden on 30 April 1890. As he wished. He was articled to a surgeon then studied medicine at University College. He gave the appearance of being a rough person. He was appointed lecturer in materia medica and botany at St. France. amongst other things. aged 69 years. He wrote papers on Luther's last illness and on the latter's famous hymn "A mighty fortress is our God". Holland on 24 October 1632. (Plate 41) CLAYTON ARBUTHNOT LANE (1868-1948) Lane studied medicine at St. investigated the toxins of mushrooms and the grafting of fruit trees. During the last fifteen years of his life he came much before the public eye as an ardent apostle of cremation. DANIEL LE CLERC (CLERICUS) (1652-1728) Le Clerc was born in Geneva. He wrote a monograph in Latin on helminthology in 1715 which was translated to English as well as a monograph with Manget on anatomy. then received the degree of doctor of medicine from the University of Valencia. He was a voluminous writer on aspects of natural history and. Switzerland in 1652. He obtained a doctorate in medicine in 1895 and entered the Indian Medical Service. He died from diabetes and a carbuncle on 30 October 1874 aged 60 years. although he did allow visiting scientists to use them. He communicated many of his findings in letters to friends and published many of his original observations in the Proceedings of the Royal Society of London. the medium in which most natural philosophers of his day published their works. In 1886 he was awarded the degree of doctor of laws by the University of Harvard. He began the study of medicine at the University of Pennsylvania and took the degree of doctor of medicine in 1844 with a thesis on the comparative anatomy of the eye of vertebrates. he was appointed to the chair of hel- . in 1671. He died in Delft on 26 August 1723 at the great age of 90 and lies buried in the Oude Kerk. the daughter of a merchant in Norwich. He joined the staff of the London School of Tropical Medicine in 1905 to found the department of helminthology. In this task he was successful. and was the first to demonstrate a parasitic protozoon when he found Giardia lamblia in his own stools. She died in 1666 then he married Cornelia. finding the snail vectors of Egyptian schistosomiasis. In 1845 he was appointed a prosector in anatomy then in 1853 he was made professor of anatomy. the son of a prosperous hatmaker of German parentage. Infusoria and Rotifera in water.804 A History of Human Helminthology shopkeeper. He never received a formal scientific training and could not write or read Latin. He began the study of biology and medicine at the University of Birmingham but then transferred to Glasgow where he graduated with bachelor degrees in science. In 1660 he received a sinecure office with the municipal authorities as City Chamberlain of Delft. Between 1912 and 1914 he was Wandsworth Scholar at the London School. the daughter of a Calvinist minister. the capillary circulation. Soon afterwards. erythrocytes. This employment provided him with ample leisure to indulge in his scientific interests. He obtained the degree of doctor of science from that University in 1911 and its doctorate of medicine in 1917. but popular with his students. he became the father of palaeontology in the United States. (Plate 45) ROBERT THOMSON LEIPER (1881-1969) Leiper was born at Kilmarnock. He made numerous observations of biological interest. at his death. He married Barbara de May. He taught himself the art of lens grinding and used simple biconvex lenses to magnify the world around him. His interest in helminthology began soon after graduation. of which he became a foreign member in 1680. In 1853 he advanced a theory of natural selection. He visited the Gold Coast (Ghana) in 1905. (Plate 44) JOSEPH LEIDY (1823-1891) Leidy was born in Philadelphia in Pennsylvania. He was a modest and retiring man. He published widely in a number of areas ranging from the structure of the liver to the fossil horse of America. He was extremely jealous of his inventions and never sold or lent them to anyone. discovering spermatozoa. United States of America in 1823. He died after a short illness in 1891. more than 400 microscopes and magnifying glasses were found. Following the outbreak of World War I. he was sent to Egypt in 1915 with the rank of lieutenant-colonel in the Royal Army Medical Corps to investigate the mode of transmission of schistosomiasis and advise on prophylaxis for the troops. Indeed. the disciplines of zoology and comparative anatomy were added to this position. by whom he had five children. England in 1654. Scotland on 17 April 1881. anticipating Darwin by several years. worked in Nigeria in 1912 and went on an expedition to China and Japan in 1914. worked with Looss in Egypt in 1907 and visited Uganda in the same year. It is said that. Shortly afterwards. medicine and surgery in 1904. Among his important contributions were his observations on the life cycles of Trichinella spiralis. Kerbert. Janicki.M. Much of Leuckart's original work is contained in his Die Parasiten des Menschen und die von ihnen herrührenden Krankheiten (Parasites of Man) which was partly translated into English. His biographers have written that he was a man of gentle voice and charm of manner who had a great sense of humour. He died on 21 May 1969 aged 88 years. and made many other contributions to helminthology. In 1868 he was commissioned as an assistant surgeon in the Medical Department of Her . Four years later he went to London as a dispenser in the German Hospital but also attended classes at University College between 1863 and 1866. (Plate 46) NATHANIEL GOTTFRIED LESKE (1751-?) Leske was born on 22 October 1751 at Muskau in lower Lausitz. It has been said that he had an unpredictability that was the delight of his friends and the despair of his opponents. warm-hearted and good-humoured man. who was professor of zoology in Freiburg. perhaps through the influence of his uncle. (present-day West) Germany where his father was a business man. including Fedchenko. He attracted a large number of brilliant pupils to Leipzig. He then went to Aberdeen and graduated in 1867 with the degrees of bachelor of medicine and master of chirurgie. His dedicated and unparalleled career over half a century inspired a fierce loyalty among his countless students and colleagues. Albans. FS Leuckart (1794-1843). but also remarked that he did not suffer fools gladly and that at times his criticisms could be acidulated. He married Ceinwen Jones in 1908 and had a son and two daughters. was director of the Institute of Agricultural Parasitology at St. After leaving school at the age of 15. He made major contributions to the comparative anatomy and classification of many invertebrates but became attracted particularly to parasitic worms. In 1847 he was appointed a lecturer in zoology at Göttingen. He was a helpful.Biographies 805 minthology in the University of London. including discovery of the insect vector of Loa loa. he was apprenticed to a pharmacist in Narbeth. In 1850 he became associate professor of zoology at Giessen and married soon after his arrival. Looss and Lutz. KARL GEORG FRIEDRICH RUDOLF LEUCKART (1822-1898) Leuckart was born on 7 October 1822 in Helmstadt in Brunswick. (Plate 47) TIMOTHY RICHARD LEWIS (1841-1886) Lewis was born at Llanboidy in Carmarthenshire in Wales on 31 October 1841. He began his studies in Göttingen in 1842 and graduated with a medical degree in 1845. He was elected a fellow of the Royal Society in 1921 and was made a Companion of the Order of St Michael and St George (C.) in 1941. Fasciola hepatica and Strongyloides stercoralis and the recognition of Onchocerca volvulus. he held this position until his retirement in 1946. He remained in Giessen until 1869 when he took the chair of zoology at Leipzig. in 1880 he established a new Zoological Institute which became famous. and was universally praised by his colleagues and former students after his death in Leipzig on 6 February 1898. He founded and edited the Journal of Helminthology and Helminthological Abstracts. aged 75 years.G. He studied in Leipzig then was appointed successively professor of natural history in 1775 then professor of economy in 1778 in the University of Leipzig. Netley. being promoted to surgeon in 1873 and surgeon-major in 1880. he travelled to Holland and took the degree of doctor of medicine from the University of Harderwijk. There he secured patrons and. Two weeks later. He remained in that country for three years. including his Systema Naturae (1735). and he established a large garden filled with many rare and exotic plants. With financial assistance from his future father-in-law. Lewis and DD Cunningham. Further. from pneumonia and septicaemia following an accidental wound which he received while performing a post-mortem examination. One of his teachers. which he regarded as immutable. the reorganization of the botanical gardens. respectively. although not a graduate. even in the twelfth edition of his Systema Naturae. He was far more interested in systematics than in mechanisms and. This interest and enthusiasm was transmitted to his son Carl and provided him with an opportunity for developing his powers of observation. He never attempted to formulate any elaborate theory of the phenomena of life. he laid down the foundations for the modern system of classification and he facilitated its implementation by developing the binary system of nomenclature.806 A History of Human Helminthology Majesty's Army. usually in conjunction with Cunningham until the latter's appointment as professor of physiology in the University of Calcutta. There Linnaeus devoted himself to teaching. were sent to Germany for 3 months then to India to study the cause of cholera. Nils Ingemarsson adopted the name Linnaeus after a great linden tree which was regarded as sacred and grew near his home. After visiting England and France. a wealthy physician in Falun. (Plate 48) CARL LINNAEUS (1707-1788) Linnaeus. he returned to Stockholm where he practised as a physician until he was appointed to the chair of botany at Uppsala University in 1741. but conceived nature as being created by God for His honour and for the blessing of mankind. then for animals in 1758. Nevertheless. he died at his home in Woolston in Southampton. While at school. was born at Råshult in Sweden on 23 May 1707. first for plants in 1753. recognizing his talent for natural science. water and earth. publishing a number of works. having received the highest marks for the British Army and Indian Medical Services. the first child of Nils and Christina Linnaeus. as was common with many rural people in that country. In 1883 he was appointed assistant professor of pathology at the Army Medical School. on 7 May 1886. by establishing the concept of species. In 1727 Linnaeus began to study medicine at the University of Lund. aged 44 years. still averred that the universe consisted of the four ancient elements of fire. and to the production of scientific works. This permitted him to indulge himself in horticulture and a study of herbs. He worked on this and other subjects in India from 1869 until 1883. which brought him immediate fame. After much tribulation. urged his family to allow him to study medicine rather than theology. He became acknowledged throughout Europe as an authority on natural sciences. His father came of peasant stock from the province of Småland and had no family name early in life. Nils was ordained a minister in 1704 and appointed curate of Råshult in 1706. In 1886 he was recommended for election as a fellow of the Royal Society. but in the following year he moved to Uppsala. his systematic classification of the animal kingdom was less successful than his arrangement of the botanical world. Many of his findings were published as appendices to the Annual Reports of the Sanitary Commissioner with the Government of India. obtained permission to lecture in botany and attracted large audiences. air. When his own . In 1879 he married and had two children. England. lived for 3 months in a screened hut erected at Ostia near Rome. controversial style brought him into conflict in turn with Railliet. Stiles. He visited Egypt in 1893 although he did not settle there until 1896 when he accepted an invitation from the government to remain in Cairo as professor of biology and parasitology. a post created especially for him in the Egyptian Government School of Medicine. there was an acrimonious dispute between his son. Illness progressively impaired his powers from the 1750's. They were eventually sold to England where they were preserved by the Linnean Society which was founded for that purpose. he took the name of von Linné. but in private life Looss was said to be a man of simple and lovable character who had many friends of many nationalities. qualifying in 1897 and obtaining the degree of doctor of medicine in 1912. (Plate 49) ARTHUR LOOSS (1861-1923) Looss was born at Chemnitz in Saxony. (Plate 50) GEORGE CARMICHAEL LOW (1872-1952) Low was born at Monifieth in Forfarshire. He was particularly concerned with trematodes. he founded the (Royal) Society of Tropical Medicine and Hygiene in 1907. where he remained for the next 34 years. He studied medicine at the University of Edinburgh. In 1900 Low. Following his death. In 1880 he entered the University of Leipzig where he studied natural science for four years under a number of authorities. He volunteered for military service and appears to have spent some time in Belgium as a captain. Looss remained in Cairo for 18 years until he was dismissed in November 1914 following the outbreak of World War I. He was a keen ornithologist. in order to demonstrate that malaria could be prevented by sleeping by night in a mosquito-proof house. library and correspondence. He died at his home in London on 21 . and the rest of his family over his herbarium. together with LW Sambon and Signor Terzi. He died in Uppsala on 10 January 1778 aged 70 years. In 1901 he travelled to the West Indies and British Guiana (Guyana) to study filariasis then in 1903 he went to Uganda with the Royal Society's Commission to seek the cause of sleeping sickness. Shortly afterwards he was appointed superintendent of the London School of Tropical Medicine. He lectured at the University of Leipzig for some years and in 1889 presented a thesis on the role of phagocytes in the degeneration of the tadpole's tail as a prelude to his appointment as Privat-docent in the Faculty of Philosophy. Scotland in 1872. but he made the major discovery of showing that hookworm larvae penetrated the intact skin. In 1891 he married Elise Lohse. His dogmatic manner and acrid. Leiper and Sambon. a well-known artist. He received a doctorate of philosophy in 1885 for his thesis on certain trematodes. In 1921 he became an honorary doctor of medicine of the University of Giessen. (present day East) Germany on 16 March 1861. Italy. including Leuckart. In his later years he was troubled greatly with asthma and he died at Giessen on 4 May 1923 at the age of 62 years. then during the eighth decade of his life he was subjected to repeated strokes which dulled his intelligence and finally paralysed him entirely.Biographies 807 country ennobled him. He was an accomplished linguist and philatelist. who had unfortunately been appointed his successor. Together with Sir James Cantlie. the son of a local manufacturer. In 1906 he married Elizabeth Nash but remained childless. but remained childless. He was a resident at the Royal Infirmary in Edinburgh then went to London to study under Manson. and is buried in its cathedral. In 1919 a post was found for him as an assistant in the Zoological Institute at Giessen. Manson. graduating with the degree of bachelor of medicine and master of chirugie in 1873. He qualified as a member of the Royal College of Surgeons in 1869 but then continued his studies at the University of Aberdeen. Leipzig and London then in 1881 returned to Brazil and began to practise in São Paulo. the son of a Scot. He proceeded to the degree of doctor of medicine of that University in 1875 and became a member (1874) then fellow (1879) of the Royal College of Physicians. In 1889 he went to Hawaii in charge of the leprosy colony on Molokai. He was the fifth of ten children and was taken to Switzerland when two years old. aged 79 years. he became assistant physician to the London Hospital. It was there that he met his future wife. George's Hospital and graduated with the degrees of bachelor of medicine and master of chirurgie with high honours in 1869. His first post was as house surgeon at the Calcutta Medical College and his last was as professor of pathology and physician at that same institution. the daughter of the doctor with whom he had served his apprenticeship. He died in 1940 following an attack of influenza. He studied for short periods in Paris. rising to the rank of surgeon lieutenant-colonel. . Subsequently he acquired a doctorate of medicine from that University. they were married in 1891 and had a son and a daughter. He was knighted in 1903 as had been his older brother Morell who was also on the staff of the London Hospital. He became an authority of diseases of the skin and of the blood. being in charge of the skin department in 1874. lecturer in pathology in 1877. In addition. and had two sons and a daughter. He began his medical training as an apprentice in Wellingborough then entered medical school at the London Hospital. After a period in Berlin. He died in Calcutta on 24 August 1895 aged 47 years. the seventh child of Stephen Mackenzie. and his wife. In 1892 he returned to São Paulo where he was appointed director of the Bacteriological Institute. In 1908 he became chief of the department of medical zoology of the Instituto Oswaldo Cruz in Rio de Janeiro where he remained until 1938 when he was forced to retire after a series of strokes and failing health. England. he was physician to the London Ophthalmic Hospital (Moorfields) from 1884-1905 and was one of the first to make routine use of the ophthalmoscope. He studied medicine at Berne University where he graduated in 1878. Margaret Frances. Stephen Mackenzie developed chronic lung disease in middle age which greatly restricted his activities and he was forced to spend the winters in Egypt. a surgeon. (Plate 51) ADOLPHO LUTZ (1855-1940) Lutz was born in Rio de Janeiro. Ann Fowler. He died at Dorking in Surrey on 3 September 1909 aged 64 years. James F McConnell. on 13 January 1848. née Harvey. Brazil in 1855 into a family which had emigrated from Switzerland in 1849. He married Helen Dulley. India. physician and lecturer in medicine in 1886 and consulting physician in 1905. He studied medicine at Aberdeen University and at St. In 1870 he joined the Indian Medical Service in Bengal where he served for the remainder of his life. an English nurse. (Plate 52) JAMES FREDERICK PARRY McCONNELL (1848-1895) McConnell was born in Agra. STEPHEN MACKENZIE (1844-1909) Stephen Mackenzie was born on 14 October 1844 in Leytonstone.808 A History of Human Helminthology July 1952. He became a member of the Royal College of Surgeons and in 1888 was elected a fellow of the Royal College of Physicians. and an old cerebral infarction. he was said to be studious but not brilliant and fond of cricket. fishing and carpentry. his body being subjected to post-mortem examination at his own request. but developed curvature of the spine and paresis of the right arm so was committed to bed for five months. recognition of lymphadenopathy. At school. he observed the development of Wuchereria bancrofti microfilariae in mosquito intermediate hosts. Despite a lack of professional and literary contact. Formosa (Taiwan) where his duties were to inspect ships at port. In 1666 he returned to Bologna. He took a leading part in the foundation of the Hong Kong College of Medicine for the Chinese and was appointed its Dean in 1887. He graduated in 1653 and remained in Bologna for several years. a small bladder calculus. (Plate 53) PATRICK MANSON (1844-1922) Manson was born on 3 October 1844 in Oldmeldrum. founded the famous London School of Tropical Medicine in 1899 and drew attention to the lateral spines of . In 1889 he returned to England and commenced practice in London the following year. In 1875 he went on leave to England and married Henrietta Isabella Thurburn. he was posted to Amoy in China. Shortly afterwards he described Filaria ozzardi. he began the study of philosophy and medicine at the University of Bologna. his father being laird of Fingask and manager of the local branch of the British Linen Bank. At the age of fourteen he was apprenticed at the ironworks of his mother's relatives. He maintained a regular correspondence with the Royal Society in England and was elected a fellow in 1668. In 1866 he was assistant medical officer at the Durham Lunatic Asylum in England and during this time wrote a doctoral thesis entitled A peculiar affection of the internal carotid artery in connexion with diseases of the brain. Manson carried out many important helminthological studies while in Amoy. Later that year he joined the Chinese Imperial Maritime Customs and was posted to Takao. the second son of nine children. In 1860 he entered the medical course at the University of Aberdeen and graduated with the degrees of bachelor of medicine and master of chirurgie in 1865. He died there in 1694. during which time he studied natural history. in 1628. At the age of 17. left ventricular hypertrophy. He was appointed physician to the Albert Dock Hospital of the Seamen's Hospital Society in 1892 and medical adviser to the Colonial Office in 1897. Messrs Blaikie Bros. Italy where his father was a small landowner. In 1656 he accepted the chair of theoretical medicine (equivalent to physiology) in Pisa then in 1662 moved to the University of Messina. by whom he had two sons and three daughters. He went on leave to Britain in 1882 then moved to Hong Kong in 1883. Aberdeenshire in Scotland. attend the native missionary hospital and conduct a private practice. On his return to the Orient.Biographies 809 MARCELLO MALPIGHI (1628-1694) Malpighi was born at Crevalcore near Bologna. in Aberdeen. found periodicity of microfilaraemia in the blood. In 1691 he went to Rome as personal physician to Pope Innocent XII. was intimately associated with Ronald Ross between 1894 and 1898 in the discovery of the mosquito transmission of malaria. maintain a meteorological record. He made many contributions to medicine and science including observations on the circulation of blood through the lungs. treat crews. In 1891 he discovered the microfilariae of Loa loa and of the worm now known as Mansonella perstans. discovered Spirometra mansoni and was associated with the recognition of Paragonimus westermani. the structure of the kidney (Malpighian corpuscles) and the liver. and studies of the anatomy of fishes and silkworms. it disclosed a scarred kidney. by all accounts. Morgagni was the founder of the discipline of pathological anatomy. then in 1927 he was made professor of medicine at the University of Tokyo. He was elected a fellow of the Royal Society in 1900 and received honorary doctorates from the Universities of Aberdeen (LL. In 1921 he was appointed clinical director to the hospital of the Institute.. For the last thirty years of his life he was affected by recurrent attacks of gout. He studied medicine in Bologna where he graduated in 1801. it summarized a lifetime study of clinical observations and of pathological studies.) in 1900 then was knighted in 1903. He graduated in medicine from the Tokyo Imperial University in 1917 then was an assistant for four years at the Hospital Clinic. While tutor of a young count. 1904). He was a scholar. a most impressive man in appearance. He was made a Companion of the Order of St Michael and St George (C.. 1886) and Oxford (D. Upon his return to Japan. Denmark. He then transferred to the Government Institute for Infectious Diseases. (Plate 55) KEINOSUKE MIYAIRI (1865-1946) Miyairi was born in Nagano-Ken. (Plate 56) GIOVANNI BATTISTA MORGAGNI (1682-1771) Morgagni was born in Forli. Japan in 1865. aged 89 years. (Plate 57) OTTO FREDERIK MÜLLER (1730-1784) Müller was born on 2 March 1730 in Copenhagen. He studied medicine at the Tokyo Imperial University and graduated in 1890. intellect and personality who was universally mourned after his death in London on 9 April 1922 at the age of 77 years. successive editions have continued to appear down to the present day. Manson was. philosopher. In 1898 the first edition of his Manual of tropical diseases appeared. investigated by anatomy) which appeared when he was 79 years old.Sc. He died at Padua on 5 December 1771. he was able to study theology then jurisprudence at the University of Copenhagen by working as a tutor for certain aristocratic families. teacher. Italy on 25 February 1682. a position which he was to hold for over 50 years.M.810 A History of Human Helminthology the eggs later recognized as Schistosoma mansoni in 1902. In 1934 he became director of the Government Institute for Infectious Diseases. He published widely but his greatest work was De sedibus et causis morborum per anatomen indagatis (The seats and causes of diseases. he was appointed professor of Hygiene at the Fukuoku College of Medicine of the Kyoto Imperial University. physician. he journeyed through . He worked in public health for a number of years then was sent to Germany between 1902 and 1904. (Plate 54) YONEJI MIYAGAWA (1885-1959) Miyagawa was born in Japan in 1885. where his father was a musician. He remained in Bologna until 1707 when he moved to Venice. Manson was the first president of the Society of Tropical Medicine and Hygiene (now the Royal Society) and has been acclaimed frequently as the "father of tropical medicine". During visits to their estates he became interested in natural history and acquired a collection of insects.D. At the age of 29 in 1711 he was elected to the chair of theoretical medicine (equivalent to physiology) at Padua then four years later he was appointed professor of anatomy in the same University. Although he grew up in poverty.G. medical historian and pathologist. In 1909 he returned to Forli and practised medicine with great success. (Plate 58) KOAN NAKAGAWA (1874-1959) Nakagawa graduated in 1894 from the department of medicine. however. LOUIS ALEXIS NORMAND (1834-1885?) Normand was born on 7 September 1834 at Clermont in Argonne. Upon his return to Denmark. He turned his attention to physics and chemistry. and in 1860 returned to Berlin to begin the study of medicine. France. He began his university training at Bonn. He practised medicine in Tokyo. Bern (1871). By 1926 he was chief medical officer to the Government and director of the largest hospital on the island. Japan in 1886. He died in 1967. He died in 1925. Following this he was called to a chair in Odessa where he investigated the living and fossilized world of South Russia. the son . He apparently suffered from hydrocephalus as a child and did not learn to speak until he was four years of age. increasing his knowledge and widening his collections. He studied medicine at the Aichi Prefectural College of Medicine.Biographies 811 Europe. Finland in 1805. He made little attempt to develop a private practice. (Plate 59) BERNHARD NAUNYN (1839-1925) Naunyn was born in Germany in 1839. he wrote Mikrographische Beiträge which dealt chiefly with parasitic crustaceans but which also considered certain parasitic trematodes. After several early appointments. the son of a well-to-do Berlin burgomaster. He studied pathology in Kyoto and later became professor of pathology at Aichi University. Königsberg (now Kaliningrad) (1872). Strasbourg (1888) and retired to Baden-Baden in 1904 as professor emeritus. In 1849 he was appointed a professor in the University of Helsingfors (Helsinki) and he died there in 1866. kind-hearted but somewhat vain man. He died in 1959. While in Berlin. graduating from there in 1913. He was recognized as one of the great clinical teachers in Germany. In 1862 he presented his inaugural thesis for the degree of doctor of medicine on the development of Echinococcus in the dog. He was generally regarded as an amiable. intending to prepare for the law. but his interests were catholic and he wrote on many clinical subjects. preferring instead to devote his great energies to the furthering of the understanding of diseases which could be studied in animals and by quantitative chemical procedures at the bedside and in the experimental laboratory. Japan until 1904 when he entered the medical service of the Formosan (Taiwanese) Government. he married into money and thereafter was able to devote himself to scholarly pursuits until his death at the age of 54 years in Copenhagen on 26 December 1784. especially the nature of jaundice and the formation of gallstones. he joined the department of medicine at universities in Dorpat (1969). MASATOMO MUTO (1886-1967) Masatomo Muto (also known as Shochi Muto) was born in Yamanashi prefecture. He studied at Åbo (now Turku) then went to Berlin where he became a pupil of Rudolphi. Fourth High School (which was the predecessor of the Kanazana Medical College). (Plate 60) ALEXANDER von NORDMANN (1805-1866) Von Nordmann was born of a Germanized Finnish family in Wiborg. He made major contributions to the understanding of diabetes mellitus. Between 1855 and 1880 he served on 20 warships. (Plate 61) ALBERT TRONSON OZZARD (?-1929) Ozzard became a member of the Royal College of Surgeons in 1886 and a licentiate of the Society of Apothecharies in the following year. He died in England on 15 October. He became famous in the eyes of the British public for his work on fossils. however. He was knighted in 1884. He left Edinburgh prematurely. he also became lecturer on comparative anatomy at St Bartholomew's Hospital. He died in London in December 1892. and oversaw its transfer to new premises in South Kensington. He was apprenticed for four years to a doctor in Lancaster then matriculated as a medical student at the University of Edinburgh in 1824. Paris. Ireland. He became a prosector for surgical lectures at St Bartholomew's Hospital in London and two years later became a member of the Royal College of Surgeons. In 1872 he entered the Royal Navy. Italy and Mexico. 1913. In 1836 he was made Hunterian professor of anatomy and physiology at the College. In 1856 he resigned to become the first superintendent of the natural history department of the British Museum. having retired in the previous year to a residence in Richmond Park that had been donated by Queen Victoria. Rochefort and Lorient. He joined the Colonial Medical Service and spent 40 years from 1887-1927 in British Guiana (Guyana) holding various posts including district medical officer and resident surgeon to the Suddie and George- . He had 20 periods of service on land including at Toulon. On 30 September 1875 he joined the Indian Medical Service as a surgeon. duplicity and ambiguity. His first appointment in 1855 was in the Naval Hospital (Hôpital de la Marine) in Toulon. third class (1855). England on 20 July 1804. Cherbourg. Marseille. physician first class (1865) and principal physician (1878). Although he set up in practice in 1826. Most of this period was spent in civil service in the Punjab Sanitary Service.812 A History of Human Helminthology of a music teacher. RICHARD OWEN (1804-1892) Owen was born at Lancaster. being promoted to surgeon-major in 1887 and surgeon lieutenant-colonel in 1895. He served with distinction against two epidemics of yellow fever on the Normandy and the Massena and took part in campaigns in the Crimea. A biographer has recorded that he was a tyrant and a prima donna possessed of deviousness. but he defended creationism in terms so ambiguous that no-one understood him. He undertook his medical studies at Queen's College in Cork. surgeon second class (1861). aged 88 years. not taking his degree. Owen attacked Darwin in 1860 over the theory of evolution. JOHN O'NEILL (1848-1913) O'Neill was born on 31 July 1848. graduating with the degrees of doctor of medicine and master of chirurgie in 1870. the son of a West Indies merchant who died while his son was still an infant. He retired from the Indian Medical Service in 1896. He enrolled in the Naval Medical School and became successively a surgeon. In 1883 he led a team of surgeons from the Bengal Army that was sent to Egypt during the cholera outbreak of 1883. serving in the Ashanti War of 1873-1874. his first love was anatomy and in the same year he became assistant conservator of the Hunterian museum of the Royal College of Surgeons. He retired at his request in 1884 while based at Lorient and is thought to have died in 1885. He was made a Chevalier de la Légion d'Honneur (knight of the legion of honour) in 1863. aged 65 years. At around the same time. broken by attacks of grave illness. he moved back to Berlin in order to be in closer touch with the scientific world and he died there on 20 Septemer 1811. French. he was curator of St. the daughter of an Anglican minister.Biographies 813 town Public Hospitals. He then spent some years in Holland and England working on zoological collections from the tropics. He studied medicine at the universities of Halle. He received his degree from the last university in 1760 with a thesis on intestinal worms. Bartholomew's and kept that post until he resigned in 1871 following a near fatal attack of cellulitis which left him weakened. He continued his education . Göttingen and Leiden. In 1847 he was appointed assistant surgeon to St. Unfortunately he contracted the infection and he remained in poor health until his death on 1 February 1929. Bartholomew's Medical School in London then in 1836 he became a member of the Royal College of Surgeons. on the immense quantity of scientific material that he had brought back with him. From 18431851 he was warden of St. JAMES PAGET (1814-1899) Paget was born at Great Yarmouth in Norfolk. (Plate 62) PETER SIMON PALLAS (1741-1811) Pallas was born in Berlin in Germany on 3 October 1741. Dutch and Italian. and two sons. He died after two years of enfeebling illness on 30 December 1899. France on 22 December 1822. In 1793 he was sent to explore the Crimean district which had just then become a part of Russia and he stayed there for a long time living on an estate that the Empress Catherine II had given him. In 1767 he was invited by the Russian government to take part in an expedition which was being sent to explore Siberia. as professor of natural history. aged 69 years. He studied at the University of Besançon. then went to St. He described Paget's Disease of the Nipple in 1874 and osteitis deformans (Paget's Disease of Bone) in 1877. Bartholomew's museum and did much writing including being sub-editor of the Medical Gazette and translating medical articles from German. In 1834 at the age of 21 he entered St. He lived a strenuous life in a tropical climate. Finally. His father was a brewer and shipowner and mayor of the town. having been made a fellow of the Royal College of Surgeons when the fellowship was instituted. He spent six years from 1768-1774 travelling in that region. (Plate 63) LOUIS PASTEUR (1822-1895) Pasteur was born at Dole in Jura. Petersburgh (now Leningrad) where he worked. leaving his widow. His last work was the investigation of a severe epidemic of malaria in the upper reaches of the Demerara River. In that year he was knighted. Bartholomew's College. daughter. Pallas was also an accomplished linguist and geologist. a surgeon in Yarmouth. He was president of many learned societies. In 1839 he nearly died of typhus. aged 85 years. the son of a tanner and a retired sergeant in Napoleon's Army. the son of a doctor. From 1847-1852 he was professor of human anatomy and surgery. he always found time to call in the aid of his microscope in the diagnosis of obscure cases. In 1844 he married Lydia North. The next few years were very difficult for him financially. the eighth child of the 17 children of Samuel and Sarah Paget. In the same year he was appointed demonstrator in morbid anatomy then in 1841 he became surgeon to the Finsbury Hospital. However great the demands of work. He was appointed surgeon to St. Bartholomew's Hospital. where he received the degree of bachelor of arts in 1842. In 1839 he was apprenticed to Mr Charles Costerton. England in 1814. He then toured France and Germany before returning to Basel where he conducted a public dissection and received the degree of doctor of medicine in 1557. He died in Pavia. He studied a variety of parasites. then his election to the position of city physician made him overseer of the public health and director of the city hospitals. aged 89 years. he served as director of the International Museum for the study of bees and wine-making. After a period of private practice he was appointed professor of clinical medicine in the University of Salvador in 1902. then from 1867 to 1899 he was professor of chemistry at the Sorbonne. France in 1552 and graduated in 1556 as a bachelor of medicine. FELIX PLATTER [PLATERUS] (1536-1614) Platter was born in Basel. He sponsored a botanical garden and established chairs in anatomy and botany at the University in Basel. he became more interested in infectious diseases. aged 72 years. His early education was undertaken in Salvador then he studied medicine at the University of Bahia. In 1571 he was appointed to the chair of the practice of medicine.814 A History of Human Helminthology in the physical sciences in Paris at the École Normale Supérieure. the son of a well-known printer in October 1536. Italy on 4 November 1936. In 1849 he was appointed professor of physics at the Lyceum in Dijon. After he left the University. When only 46 years of age in 1868 he had a stroke which left him partially paralysed on one side of his body. (Plate 65) MANOEL AUGUSTO PIRAJÁ DA SILVA (1873-1961) Pirajá da Silva was born in the town of Camamn near Bahia. he refused to consider mental disturbances . He died seven years later on 28 September 1895. It was here that he studied fermentation and showed that yeast cells were required for the production of alcohol. and developed a vaccine against rabies. He was appointed professor of veterinary pathological anatomy in the University of Turin in 1874 and remained there until his retirement 48 years later in 1922. A few years later he was appointed professor of parasitology in the medical school in Bahia. In 1852 he moved to Strasbourg as professor of chemistry. As the years passed. In 1857 he was recalled to Paris to direct the scientific studies of the École Normale. and with impaired speech. Echinococcus and Trichinella. He studied at the University of Turin and received a degree in veterinary medicine in 1867. In 1888 the Pasteur Institute was opened as a monument to Pasteur funded by public subscriptions. He died in 1961. (Plate 64) EDOARDO PERRONCITO (1847-1936) Perroncito was born on 1 March 1847 at Viale d'Asti in Italy. he began the study of medicine in Montpellier. It was during this period that he established the causal relationship of micro-organisms with infectious diseases. After receiving a classical education. he displayed exceptional courage during successive outbreaks of plague. In 1863 he was professor of geology and chemistry at the École des Beaux Arts. In this capacity. where he remained until his retirement in 1935. from which he received a doctorate of philosophy in 1848. He was a prolific author on medical subjects. proposed a classification of psychiatric disorders (unlike most of his contemporaries. particularly hookworm. identifying Staphylococcus aureus in boils and Streptococcus pyogenes fever. In 1854 he became professor of chemistry and dean of the Faculty of Sciences in Lille. and at the Sorbonne. Switzerland. at the Chateau Villeneuve-l'Étang near Paris. Brazil in 1873. His interests were wide-ranging and in addition to parasitology he studied a variety of microbiological and botanical problems. Taenia saginata. He died in 1925. London where he graduated with the degree of bachelor of medicine in 1848. He died in Basel on 28 July 1614. aged 77 years. (Plate 67) BRAYTON HOWARD RANSOM (1879-1925) Ransom was born in Iowa. however. In 1860 he married Elizabeth Branwell by whom he had four sons and one daughter. Egypt. and described cretinism. then after an apprenticeship with a doctor at King's Lynn. During this period he gained the degree of doctor of medicine from the University of London and was elected a fellow of the Royal College of Physicians in 1869. studied at University College. He was the first to experiment with snake venom. for this work he was elected a fellow of the Royal Society in 1870. He died in Nottingham on 16 April 1907 at the age of 83 years. United States Department of Agriculture. the son of a doctor. He became an intimate of the court of the Grand Duke of Tuscany at the age of 26. graduating in 1830. (Plate 69) WILLIAM HENRY RANSOM (1823-1907) Ransom was born at Cromer. He went to school in Norwich. After travelling through France and Germany on a study tour. but from eggs laid . He travelled to Paris then in 1832 was appointed professor of anatomy and physiology in Cairo. He spent the next five years in travelling. aged 79 years.Biographies 815 to be the work of demons). but was not made "medico primo" until 1666 when his father died. He died on 29 September 1882. D. the son of a civil servant. studying languages. (Plate 66) FRANZ PRUNER (1803-1882) Pruner was born on 8 March 1803 at Pfreimdt in Oberfalz. not in consequence of putrefaction. When he was a boy he was educated in the Jesuit schools then he took the degrees of doctor of medicine and doctor of philosophy from the University of Pisa in 1647. During the early years of his practice. His greatest work. He was a great man of science and a brilliant investigator. United States of America in 1879. lay in other directions. and writing poetry.C. England on 19 November 1823. the son of Henry Ransom. He proved that worms in rotting meat arise. He was educated at the University of Nebraska from where he received the degree of doctor of philosophy in 1908. He was a wise and skilful physician and had a healthy scepticism about the value of many of the therapeutic agents then available. Two years later he became the director of the Military Hospital in Esbegyeh near Cairo then subsequently director of the Kasr-el-Aini Central Hospital in Cairo where he was also professor of ophthalmology. (Plate 70) FRANCESCO REDI (1626-1697) Redi was born at Arezzo. In 1902 he moved to George Washington Medical School in Washington. He studied medicine in Munich from 1826. Tuscany in Italy on 18 February 1626. he settled in Nottingham in 1850 and became physician to the General Hospital between 1854 and 1890. he devoted much of his spare time to studying the embryology of fishes and the development of galls in plants. becoming chief of the zoology division in 1906. He then joined the Bureau of Animal Industry. finding that it was innocuous by mouth but toxic when applied parenterally. amongst many other observations. Germany. a master mariner. He was a reticent person and fastidious about his appearance. then was called to Berlin as professor of anatomy and physiology in 1810. (Plate 71) RODOLFO ROBLES (1878-1839) Robles was born in Quezaltenago in Guatemala in 1878. Some of Redi's experiments were inconclusive and he accepted that certain intestinal worms and gall-flies may arise by spontaneous generation. and physiology.816 A History of Human Helminthology by flies on the meat. he was appointed professor of obstetrics at the University of Göttingen in (West) Germany. the eldest daughter of the Burgomaster of Greifswald. He then studied medicine in Jena. graduating in 1750. as it exacted blind faith and put a limit to his logic". comparative anatomy. He studied at Greifswald University where he took the doctorate of philosophy in 1793. Friederike Eleonore Wilhelmi. In 1754. Redi never married. having finished a course at the Berlin Veterinary School. He returned to Strasbourg as an obstetrician. After his second wife died in 1821. by whom he had two daughters. but his most important work may have been his textbook on physiology. aged 61 years. He returned to his home town to practise but in 1911 moved to Guatemala City where he carried on a private practice while holding various positions in the Faculty of Medicine. He studied medicine in France. Entozoorum. then his Entozoorum Synopsis was published in 1819. He was accorded a public funeral and was buried in the church of San Francesco at Arezzo. His father was a schoolmaster who later became a pastor near Stralsund in the part of Pomerania which was then within the Swedish kingdom (now East Germany). Sweden of German parents on 14 July 1771. Erlangen and Göttingen. France in 1726. then presented his thesis entitled Sur les vers intestinaux for the degree of doctor of medicine at Griefswald. which occupied his old age and was still unfinished at his death. graduating in 1904. Subsequently he studied in England and Holland. (Plate 73) . Grundriss der Physiologie. and his death occurred suddenly on the night of 28 February 1697 when he was with the court at Pisa. He died in 1939. Dresden. His first parasitological opus. He made important contributions in three main areas . He was appointed professor of medicine at that University in 1808. appeared between 1808 and 1810. Here he founded the Berlin Zoological Museum and under his influence Berlin became a great centre for the study of human and comparative anatomy. CARL ASMUND RUDOLPHI (1771-1832) Rudolphi was born in Stockholm. Émil Brumpt. aged 71 years. first to his cousin.parasitology. but laboured hard for the abolition of the mysticism that natural philosophy had introduced into biology. During the last nine years of his life he suffered much from epilepsy. then he later married Charlotte Friederike Wilhelmie Meyer. Rudolphi's own health became poor and he died in Berlin on 29 November 1832. United States of America. He could never persuade himself to perform vivisections. JOHANNES GEORGE ROEDERER (1726-1763) Roederer was born in Strasbourg. Rudolphi married twice. Bigelow. According to his translator. his "constant friendship for the Jesuits must have had a maleficent effect on (his) mind. Most of his schooling was undertaken in Guatemala but he spent a brief period in California. sive vermium intestinalium historia naturalis. He studied medicine in Paris. He died in Strasbourg in 1763. She died in 1801. he was appointed a professor in the Veterinary Institute in Griefswald. In 1801. Here he came under the influence of the famous French parasitologist. she died in 1854 and in the following year he married her younger sister. Germany (now Wroclaw. While still young he went with his family to Italy then studied medicine at the University of Pisa. After the death of his father he had financial problems and practised medicine for some years at Heilsberg. Poland). then moved to Munich where a chair of physiology and comparative anatomy was established in 1856. for this service he was decorated by both the French and Italian governments. In the same year he moved to Freiburg as professor of zoology. In 1840 he was called to Erlangen as professor of zoology. During this period he devoted much of his spare time to zoological studies and the collection of insects and helminths. he died in Munich on 7 April 1885.Biographies 817 LOUIS WESTENRA SAMBON (1866-1931) Sambon was born in London. He graduated from there with the degree of doctor of medicine in 1891. working in public health and editing a medical journal called Imparziale. In 1850 he became professor of physiology and director of the Physiological Institute at Breslau. In 1873 he went to Cairo. Tunisia of Italian parents. Poland). Nevertheless. and not the climate. the journal Zeitschrift für wissenschaftliche Zoologie. East Prussia (now Lidzbark. He died suddenly in Paris on 31 August 1931 at the age of 65 years. much against the wishes of his father. There. In 1834 went to Königsberg (Kaliningrad) but after a short period he became director of the midwifery school in Danzig where he remained for six years. (Plate 76) PROSPERO SONSINO (1835-1901) Sonsino was born on 6 August 1835 at Tunis. according to a biographer. with Albert Kölliker. In 1836 he discovered ciliated epithelium in man when examining an extirpated nasal polyp. a famous obstetrician who was later to found the Lying-in Hospital in Berlin. Bartholomew's Hospital in London but then went to the University of Naples where his father had Italian relations. comparative anatomy and veterinary medicine. the son of an Englishwoman and a Frenchman. In 1845 he established the class Protozoa which he characterized as unicellular animals. (present day West) Germany. but the lure of England proved too strong and he went to London. He received his preliminary medical training at St. he was an accomplished epidemiologist and. While still a student in Naples. a warm-hearted and courteous man. He then settled in Florence. the son of Adam Elias von Siebold. (Plate 75) CARL THEODOR ERNST von SIEBOLD (1804-1885) Von Siebold was born on 16 February 1804 at Würzburg. He studied medicine at Göttingen and Berlin and took his degree from the latter university in 1828. contrary to universal opinion at the time. he met Manson and a strong friendship sprang up between them. Antoynie. He nearly ruined his career at the outset by publishing an article on acclimatization in which he held. After some years of ill-health with his mental faculties gradually deteriorating. aged 81 years. In 1831 he married Fanny Nöldechen. but time did not deal so kindly with his attempts to prove that pellagra was caused by an insect-borne parasite. He was eventualy vindicated in this matter. killed the white man in the tropics. or in his beliefs concerning the parasitic nature of cancer and in the existence of cancer houses and cancer streets. that parasites. He began his professional career as a gynaecologist in Rome. physiology and special physiology. he worked through a terrible cholera epidemic which afflicted the city. There he founded in 1848. comparative anatomy. Egypt and studied aspects of parasitology at the . Between 1860 and 1864 he practised in Turkey and other parts of Asia minor. England in 1866. He then returned to Africa to study schistosomiasis and in 1897 he once more visited Egypt. These investigations led to a chair in natural history at the University of Pavia in 1769. He died in Pavia on 11 February 1799. Scotland. Jutland and Norway in which he gathered material for his courses on mineralogy and botany at the Soro Academy where he taught for six years. He died in 1937. aged 66 years. (Plate 77) LAZZARO SPALLANZANI (1729-1799) Spallanzani was born in Scandiano in northern Italy on 12 January 1729. (Plate 80) . the son of a lawyer. USSR) in 1871. the first was a classic work on Scandinavian bog research and the second was his Alternation of Generations (Om Fortplantning og Udvikling gjennem vexlende Generations Raekker. He made many contributions to medical science including observations on the digestive power of saliva and gastric juices and he discovered the passage of blood through the capillaries. including botanical. JOHANNES JAPETUS SMITH STEENSTRUP (1813-1897) Steenstrup was born. biology and experimental physiology. he was eventually made an abbott. (Plate 78) DIMTRY F SSINITZIN (1871-1937) Ssinitzin was born in Symferolpol in the Crimea in the Russian Empire (now Simferopol. In 1842 he published two books which brought him fame. working in diverse fields of research. He lived in poverty for some time but then obtained employment as a technician at the American Museum of Natural History. en saeregen Form for Opfostringen i de lavere Dyreklasser) in marine life and trematode worms. He studied at the University of Warsaw. He then studied law at the University of Bologna but his interest turned to science and he became a brilliant investigator in geology. In 1846 he was appointed professor of zoology at the University of Copenhagen. He studied the Infusoria with the microscope and rejected the theory of spontaneous generation. He was appointed a professor in Shanjasky University in Moscow. Later. His interests were catholic and his investigations widespread.818 A History of Human Helminthology Khedivial Laboratory. then became Chancellor of Nijny-Novgorod University from 1918-1919. where he died on 19 November 1901. He worked heroically during the cholera epidemic of 1882. he became an associate zoologist at the Bureau of Animal Industry in Washington. which was then part of Russia. geological and archaeological studies of peat moss and the discovery of ancient Stone Age shell mounds. aged 70 years. being one of the few Europeans who refused to leave Cairo. He took no university degree but undertook journeys of exploration in Ireland. He studied in Copenhagen then became a schoolmaster for some years. Political change forced him to leave the USSR in 1923 and he sought asylum in the United States of America at the age of 52 years. then in 1848 became director of the Museum of Natural History. Finally. and later received his doctorate in zoology from the University of St. He left Egypt in 1885 and travelled as a ship's doctor to South America and eastern Asia. he moved to California where he engaged in private research. the son of a minister. He was an extraordinarily gifted and many-sided investigator. He attended the Jesuit College at Reggio where he was ordained a priest. D. He finally retired to Montepiano in Italy. Petersburgh (Leningrad). He died on 20 June 1897.C. at Vang in Jutland in Denmark on 8 March 1813. and Leipzig (1889-1890). In 1898 he returned to Berlin for two years as a scientific attaché. His time abroad. When he was seventeen years of age he followed in his father's footsteps and was sent to Aberdeen University to study medicine. and died in Amsterdam of a wasting disease at the early age of 43 years on 17 February 1680. He qualified in 1887. of which he classified more than 3. together with a delight in wearing uniforms adorned with a sword and other embellishments. CLAIR SYMMERS (1863-1937) Symmers was born of Scottish parents in South Carolina. In 1902 he joined the United States Public Health Service. he came under the spell of a religious fanatic and renounced science. He died in 1941. He studied medicine at the University of St Andrews and at the University of Edinburgh from which he graduated in 1904 with the degrees of bachelor of medicine and bachelor of chirurgie. then assisted a country practitioner in Shaftesbury. his sight became affected and he had to depend upon lectures and his fellow students reading to him. He immediately joined the Indian Medical Service. He was Officer Commanding of the Indian Station Hospital in Quetta (now in Pakistan) before his retirement from the Service in 1921.Biographies 819 FRANCIS HUGH STEWART (1879-1951) Stewart was born in 1879. He studied medicine at the University of Leiden and qualified as a candidate in medicine in 1663 but was plagued by chronic ill-health. destroying many manuscripts. He then returned to the United States in 1892 as a zoologist in the Department of Agriculture's Bureau of Animal Industry. He was a skilled sketcher and those drawings formed the basis of his masterpiece General History of Insects. CHARLES WARDELL STILES (1867-1941) Stiles was born in the United States of America in 1867. He served as secretary of the International Commission on Zoological Nomenclature for many years. He subsequently worked at Pasteur's laboratory in Paris. Dorset. He obtained his doctorate of philosophy in 1890 in the last-named. the son of a methodist minister. In 1665 he visited France seeking a cure then returned to Holland to continue his studies and graduated with the degree of doctor of medicine in 1667. in Birmingham. He was disinherited by his father. Five years or so before his death. While in Aberdeen. His tertiary education was undertaken in a number of institutions in America and Europe including the Wesleyan University in Connecticut (1885-1886). Holland on 12 February 1637. especially in Germany had stamped a military bearing on him. United States of America in 1863. in which he showed that stimulation of the nerve caused contraction of an isolated frog muscle. He did not practise medicine but continued the collection and anatomical investigation of lower forms of life. He died in 1951. (Plate 82) WILLIAM ST.000 forms. He was medical officer to a number of regiments and saw active service on the northeastern frontier of India from 1911-1912 and in several Asian and African fronts during World War I. having worked under Leuckart. especially insects. the son of an apothecary who was also a keen student of natural history. (Plate 81) JAN SWAMMERDAM (1637-1680) Swammerdam was born in Amsterdam. ultimately becoming its medical director in 1930. He anticipated Galvani in an experiment that was not published until many years later. and at the Lister . Subsequently he spent some time at the Trieste Zoological Institute and the Pasteur Institute. where he remained for the next thirty years. human anatomy. and is buried in St. He translated many works. He then studied medicine and graduated as a bachelor of medicine in 1677. London. he discovered the intermediate host of Fasciola hepatica. Tyson distinguished for the first time the anthropoid apes as a group separate from both monkeys and man. He entered Oxford University in 1667 and graduated with a bachelor of arts (1670). and received the degree of doctor of medicine from Cambridge University in the same year. His students nicknamed him "The Man". His . a bachelor. He returned to the United Kingdom in 1904 and was appointed professor of pathology at Queen's College. New Zealand. for example.1240-1311) Villanovanus was born in Aragon. or 30 January 1651 in the Gregorian calendar).820 A History of Human Helminthology Institute. While a demonstrator there. As a young man. Tyson died. and comparative anatomy. he was appointed as the first professor of biology and geology at the University in Auckland. In 1897 he was appointed professor of pathology and bacteriology at the Government Medical School in Cairo and pathologist to the government hospital. France. (Plate 83) ALGERNON PHILLIPS WITHIEL THOMAS (1857-1937) Thomas was born in England in 1857 and received his training in biology at the University of Oxford. aged 58 years.. to recite most of the Aeneid in Latin. Tyson made major contributions to medicine. Shortly before his death in 1937. He died in Belfast at the age of 70 years. and as professor of bacteriology at the Grant Medical College. he was knighted for his contributions to education. on 18 August 1708 in London. Between 1908 and 1915 he held a number of appointments as doctor on plague duty at the Bombay Bacteriological Laboratory. then master of arts (1673). (Plate 84) DYNESHVAR ATMARAN TURKHUD (1868-1926) Turkhud was born in India in 1868 but studied medicine at the University of Edinburgh. at the Matunga leprosarium.000 pounds sterling per annum for his laboratory and all his expenses. Scotland. Thereupon he went to London to practise medicine. England on 20 January 1650 (according to the English calendar of that period. He was a voracious reader and had an amazing memory. independently of Leuckart. perhaps the most important publication in the last discipline being his monograph on the orang-utan. Belfast in Ireland. being able. ARNAULDT DE VILLENEUVE) (c. He died later that year. Shortly afterwards. In 1684 he was appointed reader in anatomy at Surgeon's Hall and appointed physician to Bethlehem and Bridewell Hospitals. In 1916 he became officiating director of the Bombay Bacteriological Laboratory and in 1926 was acting director of the King Institute of Preventive Medicine in Madras. published in 1699. Spain around 1240 AD. Dionis Backchurch. By 1281 he was physician to Peter III of Aragon. including those of Galen and Avicenna from Arabic into Latin. In this work. he studied in Montpellier. In 1291 he took up residence in Monpellier but was called back repeatedly to Spain. EDWARD TYSON (1650-1708) Tyson was born in Bristol. he was sent to Egypt to study the problem of cattle plague. (Plate 85) VILLANOVANUS (ARNALD OF VILLANOVA. Lime St. While employed as an assistant bacteriologist at the latter institution. was elected a fellow of the Royal Society in 1680. being allowed l8. He died on 6 September 1311 at sea off Genoa. He died in Berlin on 5 September 1902. and was allowed to perform post-mortem examinations. These views revolutionized pathology and he became known as the "Father of Modern Pathology". (Plate 87) HELENOR CAMPBELL WILDER (1895-) Wilder was born at Baltimore in Maryland. Virchow championed the principle of cellular pathology. RUDOLPH VIRCHOW (1821-1902) Virchow was born in Schivelbein in Pomerania in present day East Germnay on 13 October 1921. aged 74 years. aged 80 years. In 1847 he was appointed prosector at the same hospital. (Plate 86) JOHANN JACOB WEPFER (1620-1695) Wepfer. He died at Schaffhausen on 26 January 1695. The Virchow Institute and the Virchow Hospital in Berlin are memorials to him. Cellular Pathology. Switzerland on 23 December 1620. and showed that cerebral haemorrhage was a cause of apoplexy (stroke). He studied humanities and medicine at Basel and Strasbourg and spent two years in Italy before receiving his medical degree from Basel University in 1647. In 1848 he had participated in an uprising in Berlin. the Parabolae. later known as the circle of Willis. was born at Schaffhausen. He served in the Reichstag from 1880 to 1893. He graduated in medicine from the University of Berlin in 1843 then served as a house officer and assistant to Froriep at the Charité Hospital in Berlin. she was made an honorary member of the American Academy of Ophthalmology and Otorhinology in view of her contributions to eye pathology. She worked for thirty years in the section of ophthalmic pathology of the Armed Forces Institute of Pathology until her retirement in 1953. United States of America. He described the anastomotic blood vessels at the base of the brain. . the son of a Canton councillor. contains many aphorisms. was appointed city physician. that cells begat cells. He returned to Schaffhausen. Wepfer rejected the speculations of his predecessors and developed an admirable scientific approach. He advanced the ideas that the basic components of tissues and organs were cells. and that diseased cells were altered in structure and biochemistry. In 1859 he accepted the chair of pathological anatomy at the University of Würzburg then in 1866 he returned to Berlin as professor of pathology and director of the Pathological Institute.Biographies 821 commitment to medicine was gradually replaced by a concern for theological matters and he spent much time travelling between Provence and Rome. In formulating his deductions from the pathological findings. His liberal political leanings led him into politics and in 1862 he joined the Prussian Lower House. In the same year Virchow and Reinhardt founded the Archiv für pathologische Anatomie und Physiologie and fü r klinische Medicin. Italy. He also became an army medical officer and personal physician to the Duke of Wirtemberg and other notables. correlating clinical features with pathological findings. He was elected as Machaon III of the Academia Naturae Curiosorum. in 1852 Reinhardt died and Virchow continued the journal on his own. Not medically qualified. In 1305 he became an adviser to Pope Clement V. the fundamental concepts of which were embedded in his 1858 work. His principal work. Portugal on 7 July 1820. He died in 1956. His wife. Possibly because of financial difficulties.822 A History of Human Helminthology OTTO EDWARD HENRY WUCHERER (1820-1873) Wucherer was born in Oporto. Portugal then in Nazareth. filariasis. he returned to Germany in 1871 and went to Stuttgart where his second wife (a sister of the first) and son were living. Bartholomew's hospital in London. Dorothea Frederica Louiza. He is buried next to his first wife in the cemetery for foreigners in Salvador. He was educated in Hamburg. then Cachoeira. died of yellow fever in 1854. and died soon afterwards on 7 May 1873. He studied medicine in both Leipzig and Heidelberg. His mother was Dutch and his father was German. he went to Formosa (Taiwan) as a lecturer in pathology. serious. He wrote on hookworm. In 1847 he returned to Bahia as the doctor to the German colony there. He died in 1898. he returned to Bahia in 1873. In 1862 he became professor of pathology at Erlangen where he remained until his retirement in 1895. becoming professor of pathology there in 1918. He suffered a stroke while attending a patient in labour. He was confronted by epidemics of yellow fever (1849) and cholera (1855). (Plate 89) FRIEDRICH ALBERT ZENKER (1825-1898) Zenker was born in Dresden in present day East Germany in 1825. modest and caring. ainhum and poisonous snakes. He graduated with honours from Okayama Medical College in 1908. (Plate 90) . He was then an assistant for a short period at St. Brazil. England following which he practised in Lisbon. The family had a business in Brazil and he lived in Bahia for seven years as a young child. (Plate 88) SADAMU YOKOGAWA (1883-1956) Yokogawa was born in Okayama Prefecture in Japan in 1883. He received an appointment in the department of pathology in the University of Leipzig but returned eventually to Dresden where he was appointed professor of pathology in the Medical-Surgical Academy. Germany where he took up an apprenticeship in pharmacy. After 24 years in Bahia. Brazil. aged 52 years. He was said to be of noble character. He then studied medicine at the University of Tübingen where he received his doctorate in 1841. After working for some time in Okayama. 400-1. 398. 707. 444.see Albertus Magnus Baelz 142. 726. 737-8 Bajon 642. 356. 554. 784 Arizono 300 Arme 631 Arthur 558 Artigas 309 Arzube 177 Asada 59. 786 Batsch 325. 652 Baker 516 Balfour 199 Bancroft J 14. 783 Arinus 119 Aristophanes 362 Aristotle 3. 710. 300. 439. 338 783 Argyll-Robertson 643. 784 Aspöck 461 Atkinson 56. 601-4. 769 Amin 629 Anaxagorus 32 Anazawa 301 Anderson R 724. 515. 526 Andry 37-8. 783 Annandale 203. 171-2. 286. 608-9. 551. 776 Beal 560 Beale 728 Beaujean 149 Beaurepaire Aragão de 624 Beaver 16-7. 786 Barbier 288 Barbot 616 Barlow C 131-8. 785 Baer von C 11. 426 Baermann 528. 730. 579. 213 Alves 216 Amato Neto 487 Amatus Lusitanius 471. 645. 610-1. 362. 372-4. 684. 783 Ackert 740 Actuarius 455 Adams 727 Aetius 356 Africa 310-1. 521. 771-3. 480 Abreu de 455-6. 356. 786 Barlow N 558 Barry 441 Barton 629 Basch 302 Bascome 618-9 Basnuevo 85 Bastian 53. 279. 739 Anderson W 486 Ando 166. 787 Baylis 203. 605 Ashburn 87. 709 Azarova 684 Aziz 680 Babione 618 Bacigalupo 425. 785 Bancroft T 55. 359. 550. 647. 386. Abbotts-Smith 405. 161-2. 108 Baer J 414. 526 Austrageliso 509 Avicenna 4. 210.PERSON INDEX Numbers in bold refer to the page on which a biography can be found. 275 Annett 613. 695. 528 Austin 90. 480. 172. 645 Anthony 740 Apt 744 Araoz 735 Aretaeus 320. 43. 77. 460 Abdallah 531 Abildgaard 41. 530 Baglivi 38 Baillet 432 Bain 735. 479 Ash 59. 32. 731 Agatharchides 694 Aitken 643 Akashi 427 Al-Qazwini 31 Albarran 207 Albertus Magnus 31-2 Albrecht 408 Alcock 609 Aldrovandi 771 Alessandrini 723 Alexinsky 335 Ali-Khan 684 Alicata 724 Allan 195-6. 304. 145. 785 Attygale 514-5 Aubert 653 Auchincloss 625 Augustine 517. 168-70. 221. 529. 649-50. 106. 709. 768. 604 Ashford 500. 469. 461. 772. 252. 433 Baumler 81 Bavay 544-6. 30. 737. 613. 31. 743. 784 Ashton 119 Askanazy 306-7. 176. 606. 433 Baellstaedt von . 745. 653. 694-5. 694-5. 787 Beer 463 Behrer 744 823 . 439. 301 Andreev 335 Andrews 520. 356. 696-7. 309. 39 Bui-Quoc-Hong 487. 399. 431. 625 Bordeu de 33 Borel 105 Borrel 776 Borrichius 370 Bour 197 Bourges de 713 Bourne 603 Boycott 516-7. 325. 682. 107-8. 409-10 Bonyun 617. 387. 328-9. 441. 680 Blanchard E 360 Blanchard R 14. 233-4. 681. 105. 54. 642. 551. 487. 618. 509. 680 Camuset 500. 790 Bonetus 338 Bonnal 431 Bonne 300-1. . 448. 668. 682. 681 Bergouie 709 Berkeley 484 Berkowitz 150-1. 521. 604. 772 Boase 678 Bobillier 339 Boerhaave 39 Bojanus 42. 104-7. 305. 473-4 Calderón 664. 207 Bernstein 346 Berrio 81 Berry 281 Bertolus 400-1 Bhaduri 731 Bhalerao Bidloo 37. 311. 705. 677. 300. 6734 Caldwell 462. 252 Bernard. 519 Bozzolo 514. 791 Bright 335 Brock 195 Brown A 676 Brown H 485. 331. 463. 672. 791 Budd 127 Bueding 87 Buffon 5. 361. 787 Bennington 311 Benoit 671 Bentley 83. 735. 487. 283. 275. 574. 643. 426. 308. 728. 771. 790 Bray 86 Brayer 78 Bremser. 561 Brown N 129 Brown P 374-5 Brown R 562. 742 Bischoff Bishop 525 Blackie 288. 526. 585. 216. 605. 388. 25. 788 Bequaert 203. 740. 405. 289. 506. 191-2. 9-10. 163. 746 Bruning 81. 678 Braun 15. 115. 668. 187-9. 365. 712 Brugmans 91 Brumpt. 424. 788 Biermer 407 Biggam. 668. 119. 22. 513 Bekhti 91 Belleli 246. 527 Brackett 287 Brady 445 Branden van den 666. 788 Billet 709 Biocca 502. 724 Brown TR 585 Browne 33 Bruce 699 Brudastov 483 Brug 16. 401-3. 791 Brenes 178 Brera 772 Breton 550 Brett 701 Brie de 103-4. 519 Biglieri 735 Bijlmer 444 Bilharz 13. 399. 424. 17. 303. 663-4. 675. 204. 211-2. 368. 4745. 613. 248 Bellingham 460. 601. 509 Cameron 59 Campbell A 429 Campbell W 92. 66970. 562 Blacklock 58. 46-7. 500. 526 Bumbalo 90 Bunnag 136. 458. 670 Bérenger-Férand 392 Berghe van den 670. 789 Blackwell 775 Blair 84. 108. 121. 678 Bucholz 105. 470. 630. 142. 524 Brunner 485 Bry de 641-2 Bryant 675-6. 251. 524. 734 789 Bloch 40. 121. 772. 580. 746 Bemrick 739 Beneden van 25. 790 Bonnsdorf von 405. 114. 298 Buchwalder 745 Buckley 287. 572. 490. 41-2. 205-8. 421-4. 440-2. 733. 389. 308 Burch 678-9 Burrass 90 Busk 127-8. 500. 245. 524. 629 Bonnet 386. 789 Bylund 92 Caelius Aurelianus 480 Caius 525 Calandruccio 54.824 A History of Human Helminthology 306. 303. 666-7. 422. 92. 267. 772. 221. 792 Cawston 203-4. 173. 427. 732 Cobbold 12-3. 287. 485. 618. 177 Crilly 523 Crocker 722 Cross 59. 588. 629. 602. 13-4. 128. 461. 77. 735. 550 Chatin 739 Chaudhuri 745 Chauvin 545-6 Chen 723 Cherry 195 Chesterman 288 Children 572 Chisolm 699. 135. 598. 130. 793 Chu 136 Chuckerbutty 600 Chung 88-9. 469. 447-8. 460. 740 Crevaux 599 Crewe 649. 305. 177-8 Church 471 Ciurea 58. 614. 701 Casaux 429 Casoni 337. 372. 648-9 Connor 709 Conor 197 Contoli 440. 528 Coulaud 92 Coulet St. 734-7. 25. 530 Danaraj 85. 484. 619. 599. 189-90. 726. 214. 705. 7378 Chabert 106. 482 Davaine 3. 128. 142. 109. 526 Deguy 663 Delafond 729 Delpert 588 Demarquay 14. 643. 772. 356. 703-4. 297 Chabaud 724. 121. 303-4. 629 Daniels 266. 792 Cerf 89. 4278. 307 Claparède 441 Clericus . 519 Catto 266-7. 599 Cupp 16-7 Currie 645 Curtis 218 Cuvier 6 D'Alessandro 346 Da Cruz Ferreira 89 Dacunha 252 Daengsvang 59. 729-30 Chang 302 Chapin 311 Chardome 58. 745 Cho 449 Choi 151 Chopra 626 Chow 152. 604. 426-7. 397. 472. 772 Conyngham 311 Cook 250 Corre 599 Correa 464 Corson 667-8. 730-1 Daland 560 Dalgetty 509. 301. 400. 441. 772. 643 Chamisso von 43. 597-600. 793 Cockin 201 Codvelle 121 Cole 134 Coleman 214 Coles 212 Collet-Meygret 728 Colomiati 514 Coneato 522 Connal 56. 623. 247. 334. 774. 108. 738-9 Charles 697-8. 458. 479. 549. 794 Darling 530. 713 Chitanondh 732 Chitwood 721. 22-3. 608-10. 286. 517. 218 Chaia 526 Chambers 302. 390. 794 Davey 725 David 605 Davies 736 Davis 449 Day 213-4. 775 Castellani 302. 738 Cort 177. 575-6. 500.Person Index Cannon 728 Capp 88 Cardanus 31 Cardoso 243 Carneri de 463 Carnochan 625 Carter H 247.see Le Clerc Clot 642 Cobb 729. 50. 399. 825 500. 217 Cerqueira Falção de 240 Céspedes 724 Ch'en 177-8. 118. 794 Democritus 32 Deschiens 550 Desnos 218 Desoil 671 Desowitz 90 Deunzer 731 . 370. 792 Chandler 221. 558 Date 445. 643 Castle 409. 606. 283. 726 Cruz 519 Cuckler 585 Culbertson 776 Cunha 526 Cunningham 309. 160-1. 278. 792 Chastang 545. 439 Coulston 429 Coventry 485 Craig 604 Cram 421 Creplin 43. 737. 170 Choyce 676-7 Christenson 286 Christopherson 83. 410. 30. 211 Celsus 3. 725. 371. 309 Dimier 709 Dinnik 463 Dioscurides Anazarbeus 77 Do Nascimento 91. 670. 11. 373. 795 Dew 333-5. 708. 189-90. 737-8 Edeson 58. 652. 696. 728. 795 Dhayaguda 629 Diamantis 212. 666. 429. 344-5. 114 Faria de 502. 796 Fayard 87. 729. 248. 702-4. 253. 737-8. 486 Fayrer 620 Fedchenko 51. 738 Dukes 739 Duncan 700 Dunsterville 190 Dunus 397 Duque Lince 462 Durme van 55. 361. Dobson 514-5 Doeveren van 359 Dollfus 297. 487. 110. 153. 742. 339. 796 Falção 298 Farber 104. 663-5. 298.826 A History of Human Helminthology Ebell 520 Eberhard 735. 365. 432 Fairley 203. 646-7. 275. 798 Dévé 333-6. 121 Fleckseder 775 Fleig 337. 267. 766. 652. 678. 337. 246. 273. 86. 283-4 Fujinami 56. 737. 646. 797 Gabucinus 31. 725. 721 Farid 210 Farquet 213 Farre 572-3. 510. 796 Dutcher 622 Dutt 712 Dyce Sharp 58. 578. 360. 747. 356. 558. 502. 675. 344-5. 737-8 . 26870. 664. 485 Elmes 310 Enzer 679 Epicurus 32 Epstein 474 Ercolani 722 Erian 216 Erlich 776 Eschricht 44. 325. 469. 439. 215-6 Diaz 682 Dick 710 Diesing 3. 797 Fukutuni 284 Fülleborn 459. 679. 242. 694. 212. 489. 651. 424. 797 Fox 620. 517. 266. 795 Dubois 423. 706 Foy 740 França 204 Friedheim 215 Friedreich 584 Frimodt-Müller 629 Fritz 485 Froelich von 301. 244. 305. 678. 743. 342. 341. 247 Fernán-Nuñez 460 Ferrara 402 Fibiger 776-7 Fiedler 581 Figueroa Marroquin 682 Filippi de 108 Finlayson 266 Finsen 335 Fischer 529. 45. 576-7. 732 Ferg 699. 319-20. 775. 556-8. 30. 681 Ducas 775 Dujardin 3. 772 Fisher 288 Fitch 616 Fitzherbert 104. 428. 726. 560 Galen 3. 680-1. 671-2. 624. 711. 735. 427 Dougherty 722 Douglas 212 Dounon 550 Dove 722 Drebbel 36 Dryden 338 Dubini 499-500. 279. 732. 443. 500. 114. 549-50. 678. 477-8. 162. 431. 478-9. 643. 739. 742 Fromman 104 Fujii Y 279 Fujii D 268. 310. 682. 737. 431. 582 Fauchard 768 Faulkner 710 Faust 16. 284. 772. 712 Ferguson 207. 796 Duke 655. 797 Fehr 357 Feng 613. 552-4. 615. 119. Dietz 299-300. 243-4. 738. 519. 448. 561. 556. 285. 461. 10. 399. 700-1 Forbes J 707-8 Foster 90. 643. 512. 605. 117. 399 Espejo 92 Esslinger 738 Ettmuller 768 Eustis 560 Fain 739. 277-9. 552. 775 Flu 239 Foley 646 Forbes D 46. 208. 577. 327. 104 Gage 554-5. 672. 615 Edgar 280 Edwards 613 Ehrenberg 243 Elgood 195 Elliot 711 Elliotson 446. 32. 470. 458. 800 Herman 524 Herrick 581. 747 Hassal 163. 798 Goldberger 312 Goldman 673 Goldsmid 743 Goldsmith 253 Golgi 549-50 Gönnert 89. 337. 209. 444. 742-3. 193-4. 440. 800 . 432. 441. 192. 365. 249-50 Giroud 87. 49 Gerritson 210 Gervais 432. 449 Gleichen-Rusworm 399 Gmelin 6. 421. 772-3. 427 Gault 629 Gayer 603 Gelpi 483 Gemma 104. 508. 611. 456. 422-5. 559 Harvey 21. 579 Henle 575 Hennessy 728 Henrard 681 Henry 431. 521. 359-60. 800 Hartsoeker 38 Hartz 459. 799 Gros 443.Person Index Galgey 734-5 Gallandat 698-9 Galli-Valerio 404 Galliard 147. 550. 696 Goddard 129. 245. 559 Galvin 489 Garcia 310-1 Garnham 683 Garrison 300. 234. 472 Grove 559 Gruby 729 Grüntzig 642 Gubler 684 Guerrero 674 Guillemard 195. 362. 500. 216. 525. 549-50. 212. 119. 303. 606. 208. 476. 710. 400. 176. 643 Gesner 104. 446. 446. 363. 512-3. 331. 402. 426. 800 Harwood 87 Hasegawa 459. 308 Harley 189-90. 144. 473-4. 48. 798 Ghalioungi 519 Ghedini 337. 521. 2056. 211-2. 526 Gordon 91. 133 Godfrey 617 Godoy 739 Goebel 442 Goeze 5. 370. 506. 368-9 Hawking 84. 544. 324-5. 775 Hewitt 85. 485. 30. 676 Gibbins 682 Gibbons 670 Giles 505-6. 148-9 Heath 699-700 Heckenroth 653 Héricourt d' 78 Heiner 745 Heller 368. 729. 726. 654 Gorter 625 Goto 277 Gouillon 737 Gouvêa de 121 Graefe von 371 Graham C 446 Graham W 713 Grassi 54. 515. 728. 503. 362-3. 679 Heydon 730 Hien 288 Highby 728 Hilton 575 Hinchcliffe 287 Hinman 559 Hippocrates 3. 517. 664. 106. 771 George de St. 216. 524. 40. 327-8. 799 Gravière de la 544 Greany 252 Grene 286 Grenet 513 Grew 36 Griesinger 190. 319. 521. 87. 356. 213 Guiness 644 Gulland 623 Gullstrand 678 Guret 578 Guyon 641-3 Guyot 642-3 György 744 Häckel 52-3 Hairston 627 Hales 92 Hall 83. 643 Hatch 197 Haubner 333. 626. 679 Heanley 129. 722 Hallez 474 Hampton 525 827 Handley 625 Harada 522 Hardy 212 Harinasuta 177. 386-8. 363. 432. 469. 775 Ghose 732 Giaquinto Mira 670. 334. 546. 522. 746-7 Gillet 289 Girardeau 562 Girges 247. 402. 646-7 Gonzalez 244 Goodsir 334 Goodwin 487. 308. 649. 578-81. 553. 584. 480. 375. 799 Harris 672 Harrison 207 Hartmann 321. 739-40. 234. 746 Herbst 50. 560. 626. 221. 174. 163. 802 Kobayashi Hisao 166. 679 Hoogstraten 740 Hooke 36 Hopkins 737 Houghton 144-5. 305. 613 Janeway 581. 525. 711 Hisette 670. 144-7. 746 Kölliker 400 Kondo 173. 342 Ho-Thi-Sang 487 Hodgkin 605 Hoekenga 462 Hoelz 424 Hoeppli 149. 460 Junod 84 Kagei 743 Kahane 460 Kakami 168 Kalantarian 747 Kalm 81 Kamo 178. 152 Huart 519 Huber 389 Hudullet 709 Huffman 643. 482-3. 611. 742. 675-6. 831 Ikeda 173 Imai 281 Imamura 173 Inouye 174 Irvine 745 Isaac 775 . 693-5 Hoffman 408 Hoffman F 733 Hoffman W 624. 489. 217. 304-6. 801 Janson 302 Jayewardene 487 Jeanselme 711 Jefferys 129 Jener 374 Jennes 642 Jiménez-Galán 178 Joannidès 213 Johansson 776 Johnson 281 Johnston 425. 802 Kholokowsky 306 Kikuiko 173 Kikuth 85. 166 Hunter 335. 584 Janicki 58. 338 Hutcheson 281 Hutchinson H 248 Hutchinson J 339 Huxley 53 Ibn Sina . 479 Kondoléon 625 Koppisan 248 Kosaka 426 Kosuge 552 Kothari 711 Kouri 119 Hirasawa 299 Hirsch 176. 744 Jophnstone G 128 Johnstone R 651 Joyeux 423-5. 271. 168. 802 Kerr 128. 801 Keller 430. 678 Hjaltelin 335. 279. 646 Humbert 48. 283. 480. 648-9 Klemm 344 Kloetzel 251 Knoch 400-1 Knott 624-5 Knox 389-90 Kobayashi Harujiro 57. 733 Hoffmann 670 Holcomb 239 Hollenbach 367 Hood 663 Hoof van 87. 308 Kershaw 676 Kevy 745 Khalil 215. 403-5. 422 Kan 281 Kartulis 246 Kasai .see Avicenna Ijima 143. 152-3. 479 Kellicott 176 Kennard 611 Kenney 464 Kérangel 513 Kerbert 162. 304. 429. 176 Koch 443-4 Kofoid 449 Koford 744 Koino 478. 746. 743 Houllier 767 Howard 510 Hsia 177 Hsieh 172 Hsu 146-7. 340. 507 Judas 389 Julien 774 Jung 16-7. 152.see Kawanishi Kasimov 741 Katamine 173 Kato 252 Katsurada 15. 253 Kau 170 Kawamura 172 Kawanishi 270. 367 Humphreys 221 Hungerford 164.828 A History of Human Helminthology Ishii 178 Issajev 705 Iturbe 243-4 Iwata 429 Jacobson 700 Jacoby 515 Jaegoerskiöld 730 James 55. 431. 521. 430. 485. 264-8. 251. 174. 169. 801 Katsuta 303 Katz 90. 561 Kimuri 170 King 733 Kingery 309 Kirby-Smith 722 Kirchner 298 Kirk 672 Kitchener Lord 200 Kleine 56. 422. 327-30. 163. 694-5. 606. 255. 201-4. 731. 218. 702. 400-1. 472-4. 665-6. 502-3. 129. 709. 286. 609-10.Person Index Kouwenaar 525. 36. 400-1. 803 Lapage 741 Lapierre 288 Larumbe 682 Lasbrey 214 Lautner 205 Laveran 545. 308-9. 261 Kuhne 589 Kuipers 725 Kumagawa 274 Kurata 281 Kurimoto 264. 445. 163. 457. 524-6. 500. 359. 776. 629 Koyama 743 Krabbe 322. 665.see Linnaeus Linschoten van 616. 579. 220. . 440. 525 Lane 303. 703-5. 577-8. 458. 239-42. 507. 473. 342. 218. 803 Leach 440 Leared 342 Lebeder 335 Lebied 649 Lee R 721-2 Leeuwenhoek 25. 5601 Langer 775 Laning 280 Lankester 127. 423. 272-4. 376. 773. 142-3. 220. 562. 774. 740-4. 128-9. 362. 302 Libby 282 Libermann 545. 706. 446. 500. 422-4. 515 Labadie-Lagrave 663 Lacroix 666-7. 506. 502. 804 Leiper 23-4. 771 Linstow von 298. 46-9. 550 Lichtenstein 16. 502. 264. 406. 549. 623. 641. 309 Lie 301 Lim 90 Lin 723 Lind 699. 805 Leuckart F 11 Leuckart R 48-51. 448. 105-6. 553. 110-1. 747. 611-2. 527. 733. 650. 645 Lombard 527 Loney 642 Looss 54-5. 510. 622. 333. 161. 665. 740-1 Lisbonne 337. 803 Leichtensern 54. 388-90. 422 Kurlow von 554 Kuwabara 151 Kwan 129 Kynsey 505. 668. 325. 481. 422. 807 Lopez 642 Loria-Cortes 725 Lortet 196-7. 332-3. 309. 517. 619. 502. 488. 130. 677. 671. 729. 392. 118. 190. 547-8. 609. 298. 145. 504-11. 199200. 548. 575. 713 Linnaeus 1. 116. 288. 217 Lambinet 510 Lämmler 89 Lamson 86-7. 746-7. 710. 470. 804 Lemoine 598 Lentz 447 Leon 301 LeRoux 288 Leske 432. 24-5. 301-3. 33. 469-70. 431. 441. 769. 698. 4. 771-2. 40. 699. 195. 522. 618 Leidy 128. 410. 746. 581-3. 341-2 Krause 523 Krehl 357 Kreis 549 Krull 59. 55. 696. 113. 129. 603. 440. 518. 615. 806 Linné von . 357. 302. 369. 647-8. 552. 53-4. 236-40. 427. 483. 372-3. 298 Küchenmeister 11-3. 643. 432-3. 110. 803 Langen de 86. 735. 662. 367. 711 Little 605 Liu 89 Livois 325 Lobo-Sanahuja 725 Locke 338 Loeper 83 Löffler 483 Logan 283. 504-5. 364-70. 56. 305. 457-8. 325. 18. 805 Li 146-7. 388. 441. 199 Lotsy 212 Low 55. 82. 697-8. 677 Laennec 325 Laigret 668 Lambert 87. 195. 805 Levine 89 Levinson 731 829 Lewis 14. 802 Kudiche 85. 197. 713. 599601. 550 Lavoipierre 649 Lawless 747 Laurie 679 Lawrie 625 Lawton 249 Le Bas 405-6 Le Clerc 38. 486. 527. 104-7. 775 Lister 707 Liston 708. 301. 115. 362. 120. 645-6. 584. 605. 808 Mackerras 59. 203. 55. 646. 650-2. 284. 731 Molin 500. 514. 662-3. 235. 713 Moquin-Tandon 189. 146. 643. 483 Minot 409 Mitter 730 Miura 252. 706.830 735-7. 2356. 482. 374-5. 196. 808 Manalang 722 Mann 280 Manson 15. 164. 278. 282 Melnikov 422 Mercer 744 Mercurialis 31 Metchnikoff 445. 322. 722. 173. 652. 776 Meydenbach 771 Meyers 629. 449 Meillon de 627 Meinhof 646. 473. 148 McKinley 622 McLelland 700 McMahon 681. 281. 703 Mantey 196 Mapes 59. 619-20. 739-40 Mongin 642. 276-7. 249. 149. 733 Magath 337. 807 Lowenthal 670. 252 MacLaurin 339 Maddern 210-1. 667-8. 599. 604-5. 361. 268. 622. 723 Mackie 207. 738 MacKay 706 Mackenzie 614. 731. 732. 301 Malebranche de 33 Malpighi 33. 289. 298 Maplestone 86. 808 McCoy 136 McDonagh 215 McGregor J 707 McGregor W 142-3. 449. 248-9. 159-62. 652 Monnig 746 Monson 178 Monti 549-50 Montpellier 666-7. 738 Meyner 421 Mhaskar 525 Milne 695 Milton 218. 175. 275. 651 Mekel 423 Meleney 267. 253 Minchin 58. 704. 274. 168. 670. 359. 530. 724 Morgagni 322. 422 Luschka 577 Lyle 195 Lýsek 490 A History of Human Helminthology 609. 105. 643-7. 683 McMullen 310 Mebius 149 Medicus 33 Meerovitxh 684 Mehlis 43. 390. 399. 363. 810 Mori 522 Morin 344 Morishita 299 Moriyasu 172 Mornex 733 Mosler 50. 706 Morenas 118 Morera 59. 682 Lu 171 Lucretius Carus 616 Ludlow 170 Lühe 309. 622-3. 726 MacCowen 561 MacCowen 88 MacDonald 505 MacFadden 668 MacFie 667-8. 302. 709. 171-2. 603-4. 736. 251. 141-3. 711. 737 Maren 84 Margolis 414 Markovic 309 Martin de la Calle 118 Martin 118. 585 Mossbrugger 460 Motte Lambert de la 698 Moty von 445 Moura de 513 Mouriquand 449 Mozley 221 MacArthur 371. 246. 270-2. 60611. 809 Manson-Bahr 87. 425 Minet 212 Minett 622 Minning 281. . 252. 428. 671. 36. 456. 604. 413 Maisonneuve 700 Maitland 625 Majima 263. 242. 2779. 706. 510. 665. 267. 734-7. 678-9 McAdam 740 McConnell 15. 508 Maegraith 285 Magalhães de 255. 108 Mehrez 87. 254. 677 Moore 59. 105. 510. 810 Miyakai 422 Miyazaki 177-8. 252 Martinéz Báez 178 Martins 244 Martirani 91. 649 Moorthy 697. 561 Matsuura 270 Matthes 745 Maung 479 Mauss 216 Maxwell 621 May 365 Mayer 216 Mazzotti 85. 626. 677. 613-5. 485 Miyagawa 272. 508. 810 Miyairi 56. 582. 323-4. 422 Napier 520 Narabayashi 276 Natterer 162 Naunyn 332. 373 Noya Benitez 253 Nwako 178 Nwokola 178 Nybelin 485 Nyberg 410 O'Connor 622 O'Neill 661-5. 480. 735 Newsham 734 Nicholas 737 Nicholl 58. 108. 546. 105. 814 . 553. 556 Oribasius 30 Orihel 59.Person Index Muangmanee 308 Muhleisen 722 Mühlens 305 Mukerji 86. 811 Normand 543-6. 726 Nishio 57. 810 Muller R 703 Müller W 727 Mullins 722 Murgatroyd 653 Murphy 409 Musgrave 460 Mustafa 483 Muto 57. 524.see Majima Nakagawa 57. 503. 303-4. 479 Oudendal 459 Owen H 728 Owen R 572-7. 393. 694 Payne A 176 Payne F 489-90. 813 Palmer E 423 Palmer ED 86 Pampiglione 562 Panarolus 362. 556-9. 107. 284. 582. 553 Parsons 663 Pasco 59. 269. 524. 300 Ogata 276 Ogawa 555 Ohba 478 Oisio 510 Okada 510 Oken 42. 471 Pane 732 Paracelsus 31. 811 Myers B 743 Myers W 614. 145-6. 769. 425 Nicholls 525 Nickerson 411 Nicolai 388 Nietzsch 42. 282 Nishigori 303. 132. 734-5. 243 Pirajá da Silva 239. 391. 527 Pallas 40-1. 731 Mukoyama 147-8 Müller H 523. 255. 487 Onabamiro 706 Onji 57. 812 Ochoterena 676 Odhner 129. 108 Okumura 428-9 Oleinikov 446 Oliver 48. 33. 148. 303-4. 529. 107. 334. 772. 625 Myrepsus 773 Nag 525 Naganori . 672. 364-5. 649. 695. 811 Nouffer 77. 137. 811 Nakahama 162-4 Nakamura 56. 671-2. 560. 811 Needham 39 Neghme 86 Nelson 273. 169. 770 Parona C 503 Parona E 423. 681. 546. 78 Pardani 711 Paré 31. 813 Paulus Aegineta 356. 813 Pagliani 514. 310-1 Noè 611 Nöller 298 Nomura 723 Nordmann von 43. 376. 304 Ozzard 506. 560. 555-6. 391 Oliver-Gonzalez 85. 300 Pasteur 51-2. 521. 664. 514. 776 Müller J 426. 243. 268. 310-1 Onuigbo 178 Ophüls 551. 737-9 Ortiz 673 Ostertag von 741 Östling 410 Otsuru 747 Ottesen 630 Otto 84. 270. 386. 814 Peruzzi 739 Pesigan 281-2 Petrushewsky 413 Philpot 443 Pickells 746 Pigafetta 642 Pigoulewski 121 Pilsbry 203. 171. 812 Ozaki 301. 562. 550. 730. 740 Payne G 538 Peacock 575 Peel 58. 738-9 Peiper 510 Pellegrino 217 Pene 91 Penner 287 Perez 309 Perez-Santiago 92 Perlingiero 744 Perrin 84 Perroncito 49. 812 Pachecho 59 831 Pachecho Luna 674 Paget 572-6. 735. 503-4. 306. 165-7. 130. 677. 430-1 Müller O 41-2. 151-2. 727. 461. 4778. 815 Redlich 404 Reichard 698 Reinhard 601 Reinus 642 Rendall 484 Renoult 209 Rep 502 Requine 3 Retzius 106 Reyher 407-8 Reyn von 746 Reynolds 710 Rhazes 694 Rhind 43. 739-40. 771. 365. 8-9. 405. 308. 41. 728. 458. 735. 306 Ringer 15. 737. 611. 776 Rim 151. 816 Sambuc 149 Samson-Hammelstjerne 722 Pirie 522 Planck 53 Plato 32 Platter 398. 298. 550 Rovelli 54. 815 Ransom W 372. 746. 426-7. 816 Ruffer 209 Ruiz Reyes 679 Rumler 362 Runeberg 407-8 Ruyschius 771 Ryuzi 151 Saboia 604 Saeki 425 Sagredo 459 Saha 745 Saito 144 Salzer 584. 476. 363. 814 Plehn 704 Pliny 3. 776. 159 Ripert 174 Rivas 652 Rivikka 86 Rivolta 306 Rizhikov 733 Ro 173 Robbins 462 Roberts J 683 Roberts W 602 Robles 58. 52-3. 325. 733. 387. 732. 7423. 320-1. 471. 469. 331. 773 Rosi 86 Ross 461. 708. 816 Rogers 651-2 Rook de 613 Rose 221 Rosen 58. 586 Salzmann 423 Sambon 16. . 414 Recio 421 Reddy 709 Redi 33-5. 647. 816 Roche 520 Rockefeller 529 Rodenburg 725 Rodenwaldt 129 Rodger 676 Rodhain 652. 668. 431. Rake 518 Raleigh 625 Ramsay G 710 Ramsay W 2 Ransom B 13. 703. 814 Puig Solanes 675 Quénu 339 Quere 677 Radomyos 300 Raffier 711 Ragni 393 Railliet 54. 772. 431-3. 456-7. 549 Rudolphi 2. 129. 712. 393. 461. 730-1 Prout 622. 114.741. 746-7. 815 Rao 301. 746. 461. 242 Posselt 344-5 Potiez 243 Pouchet 49. 666. 459. 681 Rodrigues 91. 356. 742. 723. 469. 678. 545. 300. 121. 694 Plutarch 694 Podjapolskaja 311 Poirier 128. 729. 302. 668-9. 663. 108. 561 Roederer 456-7. 742. 308 Poltera 728 Pons 250 Porter 204. 774. 422-3. 664. 665 Pruner 500. 500. 77.832 A History of Human Helminthology 484. 664 726. 422. 728. 605-6. 672-4. 480. 731 Rathouis 129 Ratz von 299 Rausch 345-6. 330-1 Powell 707 Poynton 605 Pratt 311 Priestley 599 Priston 282 Proffit 485 Prommas 59. 681. 732 Rosenberg 402 Rosenblatt 605 Rosenstein 359. 459. 174. 653 Roubaud 704 Roupell 571 Roussel 709 Roux 150. 403-5. 82. 236-8. 480 Rhoads 519 Ricciardi 562 Richard-Lenoble 739 Richards 213 Richter 472 Ridley 675 Rieder 523. 309. 351. 772. 104. 672. 30. 612-3 Roth 373. 480. 731. 460. 742-3. Earl of 338 Shaldon 247 Shaw 215 Shillinger 87 Shimura 555 Shirai 114. 500. 365. 550. 424. 512 Stone 722 Stossich 740 Stransky 281 Straub 525 Stricker 443 Ströbel 585 Strom 299 Strong 670. 90. 506. 270-2. 442. 357. 308. 422. 360. 741. 817 Spiegel van der . 746 Schraufstätter 89. 312. 729 Smillie 517 Smith A 500.see Spigelius Spigelius 32. 457. 234. 713. 198-9. 234. 430. 733 Swellengrebel 443. 743 Swammerdam 33. 483. 723 Sanders 282 Sandground 300. 516-8. 624. 287. 738. 412. 678 Simonds 108.Person Index Sandares 59. 449. 187-8. 274. 817 Sooley 283 Sorel 707 Sorenson 445 Spallanzani 39. 577-8. 311. 678 Silva Araujo 55 Silva Lima da 598-9 Simon 665-6. 726. 176. 514. 561 Swayne 484 Sweet 706. 44-5. 302. 500. 818 Stadelmann 741 Standen 449 Stanley 573 Steenstrup 13. 817 Siegenthaler 684 Silva 676. 505. 508 Sangalli 506 Santiago-Stevenson 85. 327-31. 287. 285. 424. 626 Santos 282 Sasa 604 Sawada 88 Schapiro 87 Schaudinn 511 Schaum 726 Schenone 91 Schiller 345 Schinz 485 Schmidt 446 Schneider A 741 Schneider H 375 Schrank 301. 108-10. 116 Sibthorpe 603 Siebold von 43-5. 747 Sandwith 304. 528-9.see Koino Suyeyasu 276 Suzuki 56. 560 Seltzer 770 Sen 732 Senn 190 Serapion 4. 268. 776 Talyzin 487 Tanabe 299. 819 Szidot 411 Taillandier 560 Takata 490 Takemoto 276-7 Talaat 89 Taliaferro 485. 421. 128. 303. 120 Singer 694 Singson 726 Sisinitsin . 310. 447. 421 Suga 162 Suganumu 624 Sui . 398. 328. 676 Stuckey 743 Stunkard 59. 664. 361. 652 Smith D 309 Smith M 745 Smith W 721 Soemmering 440. 375 Schrecker 213 Schreiber 42. 746. 443. 448 Solander 769 Sommer 360 Sonsino 195. 327. 549. 601. 47-8. 643. 818 Stewart I 747 Stiles 163. 819 Stock 213 Stoll 87. 557-8. 818 Stein von 48.see Ssinitzin Skrjabin 299. 550. 524 Schulthess 504 Scott 743 Scott H 517 Scowden 559 Scribonius Largus 766 Seifert 547-8. 310 Tang 427 . 475-8. 673. 428. 470. 109. 303. 728. 771 Spillman 483 Spooner 424 Spöring 399-400 Sprent 489 Spruit 462 Ssinitzin 115-6. 256 Sergent 737 Servantie 118 Seurat 604 Shaftesbut. 400. 401 833 Stejksal von 775 Stekhoven 555 Stevenson 649 Stewart F 444. 819 Swartzwelder 87. 35-6. 447 Swift 721 Symmers 246-8. 610. 744. 86 Schubart 400 Schüffner 81. 709. 369. 413 Tardieux 150 Tayler-Jones 428 Taylor 286 Teissier 553 Tennent 698 Termakov 464 Tesch 283. 57981. 356 Théoridès 91 Thiel van 725 Thienpont 91 Thira 555. 432. 128. 775 Thoonis 87 Thorensen 340 Thorpe 674 Tiedemann 575 Todokoro 284 Tomita 562 Topley 526 Toroella 678. 710. 357-9. 364. 300 Thayer 551 Theophrastus 77. 204. 820 Villeneuve de . 589. 323. 324 Thompson 201. 307. 80. 732 Warren E 203-4 Warren K 249 Wassell 431 Watkins-Pitchford 203 Watson 311 Watson-Wemyss 149 Wawruch 388. 298. 305. 774 Weingarten 629 Weinland 110. 549. 109 Wagler 327. 552 Tansurat 731 Tarassov 407. 725-6 Trent 618 Trewn 708 Tsamis 216 Tsao 178 Tsujuki 169 Tsykalas 216 Tubangui 59. 681 Ward 118. 119-21. 558 Thomas A 53. 199 Vic-Dupont 288 Vilela 561 Viljoen 377 Villanovanus 31. 115. 744 Westerman 162-3 Weston 92 Whalen 726 Wharton 362 Wherry 643 White A 449 White G 722 White R 449 Whitmarsh 622 Wielinga 725 Wilder 744-5. 337. 135-6 Walther 583 Walton 485 Wang 151. 661. 642. 177-8. 172 Wanson 670. 330-1 Vervoort 486 Vialleton 197. 820 . 484 Unterberger 473 Upatham 308 Vaillant 426 Vallisnerius 38. 456.834 A History of Human Helminthology Uchimara 425 Ulrich 461. 459. 821 Wiley 215 Willach 740 Williams C 515 Williams F 212 Williams O 744 Willius 114 Wilms 54. 321-2. 820 Turner 615 Tyson 35. 344. 423-4 Welch 92 Weller 445 Wepfer 105. 129.see Villanovanus Virchow 50-1. 110-3. 704-5. 356. 300-1 Tukalewski 463 Tullis 485 Tulp 357 Turkhud 56. 772 Wakeshima 168 Waldeck 584 Walker B 275 Walker J 130. 275. 345. 682 Torres Estrada 678 Tötterman 409 Travassos 297. 771 Verloren 400 Verrier 49. 373. 176-7 309. 386 Vanda de la 711 Vandepitte 310 Vandyke Carter 614 Veglia 288 Veiga de 695 Velden van den 775 Velschius 694-5. 771. 483 Vogt 11 Wagener 50. 469. 281. 821 Werner 363. 190. 820 Thomas H 92 Thomas J 332. 820 Virik 310 Vix 441 Voelker 177-8 Voge 288 Vogel 59. 471. 370. 733 Webb 629-30 Webbe 221 Wedl 484 Weinberg 118. 477-9. 744. 445 Wrisberg 456 Wu 170 Wucherer 81. 264 Yamaguti 730 Yarwood 310 Yeh 737 Yokogawa M 168. 725. 623. 428-9. 363. 822 Yorke 737 Yoshida 119. 275. 554 835 Yoshimoto 281 Yoshino 369-70 Young 740 Zancarol 207. 771 Yamada 172. 821 Wundt 442 Wurtz 707 Wykoff 59. 523. 428 Yamagiwa 169. 526. 555. 457. 746 Zenker 50. 447. 16670. 581. 729. 166. 173. 598600. 510. 172.Person Index Wilson 615 Wiltschur 408 Winogradoff 306 Winter 629 Witenberg 311 Wolff 197 Wolffhüggel 433 Wolfs 289 Wolphius 398 Wood 582 Woodland 425 Woodruff 653. 442-4. 169. 235. 822 Zimmerman 422 Zschukke 675 Zuelzer 744 Zune 735 Zurn 432 . 308. 677 Wordsworth 368 Wormald 571. 432. 176 Yokogawa S 56-7. 325. 573 Wright 86. 173. 275. 583-4. 5023. 513. 726. 303-6. 579. 500. 5867. 245 Zeder 6-7. see Bithynia Alternation of generations 43-5. 282. 327 Alyselminthus crassiceps 432 Amphimerus pseudofelineus 309 Amphistomum hominis 302 Anacardium. 737 Acanthocheilonema streptocerca 738 Acantogobius 304 Acerina 402 Achatina 723 Achillurbania nouveli 297. 520 Abiogenesis 29 Abramis 307 Acanthocephala 2.SUBJEC T INDEX . pernicious 407-10 Anatrichosoma cutanea 721 Anchylostoma duodenale 13 Anchylostomum duodenale 501 Ancylostoma braziliense 502. 213. 374 Arion ater 111 Armigerus 244 Arsenicals 84. 311 Achillurbania recondita 297 Acis 423 Acriflavine 216 Acupuncture 772 Aedes 605. iron deficiency 512-20 Anaemia.see antimonials Antimonials 83. 501 Annelida 2 Anopheles 612-3 Anthelmintics see also individual anthelmintics traditional 75-82 1800-99 82 1900-24 82-4 1925-49 84-8 1950-74 88-92 1975+ 92 Anthiomaline . 545-6 Anguillula stercorale 544 Anguillula stercoralis 13. 613 Afroplanorbis 243 Agamofilaria streptocerca 738 Agchylostoma duodenale 500 Agchylostomum ceylanicum 502 Alaria 297 Albendazole 91 Alocima .see cashew nut oil Anaemia. 721-2 Ancylostoma caninum 510-1. 109. 214-6. 544-6 Anisakiasis 725 Anisakis marina 725 Anisakis simplex 725 Anisus 301 Ankylostoma duodenale 12. 711 Artemisia 77 836 . 722 Ancylostoma ceylanicum 502 Ancylostoma duodenale anaemia 512-22 clinical features 520-2 diagnosis 522-3 discovery 499-501 epidemiology 527-8 landmarks 540-1 life cycle 502-10 nomenclature 500-1 pathology 510-20 prevention 528-31 synopsis 499 treatment 523-7 Ancylostoma malayanum 723 Ancylostomiasis 499-541 Ancylostomum duodenale 501 Angiostrongylus cantonensis 723-4 Angiostrongylus costaricensis 724-5 Anguillula intestinalis 13. oil of .. 711 Ants 298.disease 209. 427 Aphanius 304 Arecha catechu 80. 8 Acanthocheilonema perstans 16. 746 Bephenium 88. 308 Cambarus 177 Cambendazole 91. 241.see Bullinus Bullinus 202-3. 588. 470 Ascaris vermicularis cauda subulata 5 Aspidium. 107. 119. oleoresin of . 746 Ascaris suum 489-90 Ascaris trichiura 457 Ascaris vermicularis 4. 486. 132. 524 Carcinus 311 Cardiocondyle 427 Cashew nut oil 84 Cephalocotylea 11 Ceratocephyllus 423. 486. 425 Cercaria 42. 561 Camphora 82 Cancer 776 Capillaria aerophila 725-5 Capillaria hepatica 726 Capillaria philippinensis 726-7 Carbon tetrachloride 83-4. 524 Chloroform 524 . 109-10. Planorbis Bismuth 83 Bithiniol 88. 286 Biogenesis 53 Biomphalaria see Heliosoma. 462. 390 Bothriocephalus liguloides 428 Bothriocephalus mansoni 428 Bothriocephalus tropicus 388 Bradybaena 302 Brugia malayi discovery 604-5 Brugia pahangi 528 Brugia patei 605 Brugia timori 605 Bulimus 146 Bulinus .see Areca Bible 30. 136. 9 Cestoidea 9 Cheilospirura 727 Cheiracanthus siamensis 731 Chenopodium. 694 Bilharzia crassa 197 Bilharzia haematobia 12. 286-8 Cestoda 2. 209.Subject Index Artyfechinostomum mehrai 309 Artyfechinostomum sufratyfex 309 Ascariasis 469-97 Ascaridia columbae 473 Ascaris canis 744 Ascaris lumbricoides clinical features 480-4 diagnosis 484-5 discovery 469-71 epidemiology 487-8 landmarks 497 life cycle 471-4 nomenclature 470. 486. 440. 307 Blackflies 667-670 Blanfordia 275-6 Blasenwürmer 7 Blicca 307 Bosmina 403 Bothriocephalus latus 9-10. 487. 189-91 Bilharzia magna 189 837 Bilharzia polonica 202. oil of 81. 173 Bithynia 146-7.see male fern Australorbis 244 Avian schistosomes 286-7 Baermann technique 428 Baginulus 724 Bandwürmer 7 Barbus 307 Beetles 423 Belascaris cati 746 Belascaris mystax 744. 287-8 Bythinella 178. 526 Bertia studeri 421 Bertiella mucronata 421 Bertiella polyordna 421 Bertiella satyri 421 Bertiella studeri 421 Betanaphthol 83. 134. 136. 473-4 pathology 474-80 prevention 488-9 synopsis 469 treatment 485-7 Ascaris maculosa 473 Ascaris marginata 473 Ascaris megalocephala 473 Ascaris mystax 473. 524 Betel nut . 362-3 life cycle 364-9 nomenclature 8. 432 Coenurus glomerulatus 431 Coenurus tenuicollis 324. 626 Culicoides 735-8 Cyclocheilichthys 308 Cyclodontostomum purvisi 727 Cyclops 403-4. 177-8. 487. 332-3. 374 Culex 604. 626. 324. 609-11. 3279. 333. 428-9. 374 Clarias 731 Classification 1-28 Clonorchiasis 141-57 Clonorchis endemicus 143 Clonorchis sinensis clinical features 149-50 diagnosis 151-1 discovery 141-3 epidemiology 152-3 landmarks 157 life cycle 143-7 nomenclature 142 pathology 147-9 prevention 153 synopsis 141 treatment 151 Coenurosis 431-2 Coenurus cerebralis 329-30. 731 Cyprinus 307 Cystica 9 Cysticercosis 355-83 Cysticercus 363 Cysticercus bovis 390. 6534. 311 Crayfish 174 Crustaceans 403-5. 330 Davainea formosana 427 Davainea madagascariensis 426-7 Demerera filaria 734 Diaptomus 403-4. 174. 412 Dibothriocephalus latus 399 Dibothrium latum 11. 433 Cysticercus finna 7 Cysticercus longicollis 432 Cysticercus pisiformis 320. 428. 393 Cysticercus cellulosae clinical features 371-2 discovery 322. 731 Ctenocephalides see Pulex Cucullanus 704 Cucurbita pepo 80. 329. 389 Conocephalus 302 Contracaecum osculatum 727 Corpse worms 769 Crabs 165-6. 679-80 Dioctophyma renale 728 Dioplongonoporus fukuokaensis 422 Dipetalonema arbuta 728 Dipetalonema ozzardi 735 Dipetalonema sprenti 728 Dipetalonema streptocerca 738 Diphetarsone 462 Diphyllobothriasis 397-419 Diphyllobothrium cordatum 428 Diphyllobothrium dalliae 414 Diphyllobothrium decipiens 430 Diphyllobothrium dendriticum 414 Diphyllobothrium erinacei 430-1 Diphyllobothrium houghtoni 430 Diphyllobothrium lanceolatum 414 Diphyllobothrium latum clinical features 405-10 diagnosis 410 differentiation 397-9 epidemiology 411-3 landmarks 419 life cycle 399-405 nomenclature 399 pernicious anaemia 407-10 prevention 413 synopsis 397 treatment 410-1 Chloroquine 85. 711-3. 613. 173 Chloxyl . 711-3. 323-4.see Hetol Chrysanthemum 78. 702-6. 333. 365-6 Cysticercus tenuicollis 320-1.838 A History of Human Helminthology Cysticercus crispus 328 Cysticercus ex taenia mediocanellata 390 Cysticercus fasciolaris 321. 363 see also Taenia solium . 399 Dichlorophene 88. 136 Dicrocoelium dendriticum 297-0 Dicrocoelium hospes 299 Diethylcarbamazine 85. 702-6. 329-30. 607. 106. 462. 326 Echinococcus simiae 325 Echinococcus simplex 326 Echinococcus veterinorum 325-6. 643 Dracunculus medinensis clinical features 707-9 diagnosis 709 discovery 693-8 epidemiology 711-3 incubation period 706-7 landmarks 720 life cycle 698-706 nomenclature 697-8 prevention 713-4 synopsis 693 treatment 709-11 Dryoptera filix mas .see also Distomum Distoma buski 14. 128 Distomum hians 108 839 Dithiazanine 88-9. 188-9 Distoma hepaticum 7 Distoma hepatis endemicum sive innocuum 142 Distoma hepatis endemicum sive perniciosum 142 Distoma heterophyes 14. see also Distomum Distoma . 160 Distoma compactum 162 Distoma conjunctum 309 Distoma cygnoides 109 Distoma endemicum 152 Distoma haematobium 12. 507 Dracontiasis .see male fern Ducks 41 Earworms 768 Ebers papyrus . 561 Dobium erinacei-europaei 431 Dochmius ankylostomum 501 Dochmius trigonocephalus 502. 729 Dirofilaria repens 729 Dirofilaria tenuis 729 Dirofilaria ursi 730 Distoma . 303 Distoma japonicum 14 Distoma nodulosum 111 Distoma pancreaticum 302 Distoma pulmonale 162 Distoma pulmonalis 162 Distoma rathouisi 129 Distoma ringeri 14. 422-3 Dipylidium cucumerinum 422 Dirofilaria conjunctivae 729 Dirofilaria immitis 612. 364.see Papyrus Ebers Echinochasma perfoliatus 299 Echinococcosis 319-53 Echinococcus altricipariens 12. 332 Echinococcus alveolaris 433-4 Echinococcus granulosus clinical features 335-6 diagnosis 337-8 discovery 319-26 epidemiology 340-1 landmarks 353 life cycle 326-33 nomenclature 325 pathology 333-5 prevention 342-3 synopsis 319 treatment 338-40 Echinococcus hominis 325-5 Echinococcus hydatidosa 326 Echinococcus multilocularis 343-6 Echinococcus polymorphus 325 Echinococcus scolicipariens 12.see metrifonate Dipylidium caninum 331.see dracunculiasis Dracunculiasis 693-720 Dracunculus loa 12. 326. 331 Echinococcus vogeli 346-7 .Subject Index Diphyllobothrium mansoni 429 Diphyllobothrium mansonoides 430 Diphyllobothrium okumari 430 Diphyllobothrium pacificum 414 Diphyllobothrium ranarum 430 Diphyllobothrium reptans 430 Diphyllobothrium ursi 414 Diplocanthus 424 Diplogonoporus grandis 422 Diploscapter coronata 729 Dipterex . 160 Distoma rude 162 Distoma sinense 14 Distoma spathulatum 142 Distoma trigonocephalum 111 Distoma viverrini 308 Distoma westermanni 163 Distomum capense 190 Distomum crassum 13. 644 Filaria immitis 729 Filaria labialis 732 Filaria lacrymalis 10. 643 Filaria malayi 604 Filaria medinensis 6 Filaria nocturna 614. 603 Filaria sanguinis hominis diurna 644 Filaria sanguinis hominis major 644 Filaria sanguinis hominis minor 644. 38 Emetine 173. oil of 524 Euparyphium melis 301 Eurytrema pancreaticum 302 Eustoma rotundatum 725 Eustrongyloides 730 Eustrongylus gigas 728 Eyeworms 768 Fasciola gigantica 121 Fasciola hepatica clinical features 116-8 diagnosis 118 discovery 103-6 epidemiology 119-20 landmarks 126 life cycle 106-14 prevention 121 synopsis 103 treatment 118-9 Fasciola hominis 6 . 216. 643 Filaria loa 14. 281 Enterobiasis 439-54 Enterobius vermicularis clinical features 444-5 diagnosis 445-6 discovery 439-40 epidemiology 446-7 landmarks 454 life cycle 440-3 nomenclature 440 pathology 443-4 prevention 447-9 synopsis 439 treatment 447-9 Entozoa 2 Epigenesis 32 Equivocal generation 29 Eriocheir 165-6 Esox 401. 601. 644 Filaria philippinensis 604-5 Filaria sanguinis hominis 13. 412 Eucalyptus.840 A History of Human Helminthology Fasciola melis 301 Fasciola revoluta 301 Fascioletta ilocanum 300 Fascioliasis 107-26 Fasciolopsiasis 127-40 Fasciolopsis buski clinical features 133-5 diagnosis 135-6 discovery 127-9 epidemiology 136-7 landmarks 140 life cycle 130-2 nomenclature 129 pathology 133-8 prevention 137 synopsis 127 treatment 136 Fasciolopsis fülleborni 129 Fasciolopsis goddardi 129 Fasciolopsis spinifera 129 Fermentation 52 Ferrisea 205 Ficus 81 Filaria bancrofti 15. 644 Filaria oculi 643 Filaria oculi humani 10. 602 Filaria demarquayi 734-6 Filaria dermathemica 662 Filaria diurna 15. 643 Filaria ozzardi 15 Filaria palpebralis 743 Filaria papillosa haematobia canis domestica 729 Filaria perstans 15. 736 Filaria sanguinis hominis nocturna 644 Filaria sanguinis hominis perstans Echinoparyphium paraulum 299 Echinoparyphium recurvatum 299 Echinostoma hortense 300 Echinostoma ilocanum 300 Echinostoma jassyense 301 Echinostoma lindoense 300 Echinostoma malayanum 309 Echoing worms 769 Eliocharis 132 Emboitement 33. see Planorbis Höllenwurm 769-70 Hookworm . 499. 561 Gigantobilharzia 287 Glossobius 731 Glottis 361 Gnathostoma hispidum 732 Gnathostoma pulchrum 732. 400-2. 309 Inermicapsifer madagascariensis 426 Infection 26 Infestation 26 . Necator Hookworm disease 499-541 Hycanthone 86. derivation of term 2-3 Helminthocorton 82 Hepaticola hepatica 726 Heterakis maculosa 473 Heterobilharzia 287 Heterodera radicicola 449-50 Heterogenesis 52 Heterogony 505-6 Heterophyes aegyptiaca 303 Heterophyes brevicaeca 311 Heterophyes heterophyes 303-4 Heterophyes katsuradai 304 Heterophyes nocens 303 Heterophyes yokogawai 305 Hetol 89. 776-7 Gnathostoma siamense 731 Gnathostoma spinigerum 730-2 Gnathostomiasis 7302 Goeffroea surinamensis cortex 82 Gordius medinensis 4 Grasshoppers 302 Gregarina 161-2 Ground-itch 509 Guinea worm . 736 Filaria subconjunctivalis 643 Filaria volvulus 15 Filaria volvulxus 662-3 Filariasis 597-640 Filix mas .see Echinococcus Hydatigera granulosus 325 Hydatigera taeniaeformis 433 Hymenolepis diminuta 423-4 Hymenolepis fraterna 425 Hymenolepis longior 425 Hymenolepis nana 424-6 Hypoderaeum conoidea 305 Hypoloberca 177 Idus 307 Illustrations of worms. 774-6 Indoplanorbis 301. 307 Hexachlorophene 89 Hexylresorcinol 86. early 771-2 Imaginary worms 765-70 Immunity 37.693-720 Gynaecophorus haematobia 189-90 Gyraulus 300 Haemonchus contortus 732 Haemostrongylus ratti 723 Hagenia abyssinica 78. 304-8. 144-5. 374 Hakenwürmer 7 Halysis lata 7 Halysis solium 7 Hampala 308 841 Haplorchis pumilio 303 Haplorchis tachui 303 Haplorchis yokogawai 303 Helicella 298 Helicorbis 302 Heliosoma 243 Helminal 486 Helminth. 525 Himasthla muehlensi 305 Hippeutis . 429 Furia infernalis 769-70 Fusaria dispar 7. 731 Fleas 423.Subject Index 644.see Male fern Fish 41. 486. 108 Gentian violet 85-6. 746 Fusaria vermicularis 7 Galumna 421 Galvinism 710 Gambusia 304 Gastrodiscoides hominis 302 Geese 44. 136. 425 Fluke 104 Formica 208 Frogs 299.see Dracunculus medinensis Guinea worm infection . 457 Fusaria lumbricoides 7 Fusaria mystax 744.see Ancylostoma. 301-2. 217 Hydatid . 462. 299. 273 Kosso . 164. 286. 213. 375. 526. 487 Lice 422 Ligula mansoni 428 Limnea 110-3 . 462. 449. 473 Leucobia 144 Levamisole 91.see Niclofolan Meningonema peruzzii 738 Mepacrine 86-7. lucanthone Misgurnus 300 Mites 421 Molluscicides 221 Monkey 189. 373. 412 Loxotrema ovatum 305 Lucanthone 86. 523 Leptodera 544 Leuciscus 307. 374 Katayama disease 279 Katayama . 426 Mesocestoides lineatus 426 Mesocestoides variabilis 926-7 Metagonimus 174 Metagonimus yokogawai 305 Metastrongylus elongatus 739 Metrifonate 89. 305 . 374 Mammomonogamus laryngeus 733 Mansonella ozzardi Mansonella perstans 736-8 Mansonella streptocerca 738 Mansonia 613 Massage 772 Mastigodes hominis 7 Mebendazole 91. 306 Menichopholan . 462. 487. Limnea .842 A History of Human Helminthology Maggots. 197 Monostomum flavum 108 Monostomum mutabile 108-9 Moon 773 Mordwurm 769-70 Morerastrongylus costaricensis 724 Mosquitoes 606-613 Moxibustion 772-3 Mugil 304 Multiceps longihamatus 433 Multiceps multiceps 432 Multiceps serialis 432 Music 370. 727 Melania 145-6.see also Limneus. 282 Lumbricus 3-4. 773 Mytilus 305 Myzelmintha 11 Infusoria 39 Intestina 4 Iron deficiency anaemia 512-20 Isalopotamon 177 Iulus 473 Ivermectin 92. 561. 680 Jericho 209 Kahun papyrus 209 Kamala 80. 253 Metronidazole 119. 524 Mallotus philippinensis 80. 216.see Leche de higueron Leche de higueron 81-2. 711 Microfilaria bolivarensis 739 Microfilaria rodhaini 739 Microfilaria semiclarum 739 Micronema deletrix 739-40 Microscope 36 Miracils . 301. 375.see Kousso Kousso 78-9 La dauve 114 Lagochilascaris minor 733 Latex of higueron . 322.see also Lymnaea Limneus 110-3 . 340. 217. 166. 324 Lymnaea 107. 301. generation of 33-5 Magic 773 Male fern 76-7.see also Lymnaea Lithoglyphosis 288. see Tricula Loaches 300 Loa loa clinical features 649-51 diagnosis 651-2 discovery 641-6 epidemiology 654 landmarks 660 life cycle 647-9 nomenclature 643 periodicity 643-7 prevention 655 synopsis 641 treatment 652-4 Loiasis 641-60 Lota 401.see hycanthone. Subject Index Nanophyes salmincola 311 Nanophyetus salmincola 311 Nanophyetus schickhobalovi 311 Nasal worms 768 Nasturtium officinale 120 Necator americanus discovery 501 nomenclature 501 see also Ancylostoma duodenale Necator suillis 740 Nematoda 1. 253 Oxantel 90 Oxytrema 311 Oxyuris "incognita" 449 Oxyuris vermicularis 10. 375.see Bithynia Paragonimiasis 159-85 Paragonimus africanus 177 Paragonimus ecuadoriensis 177 Paragonimus heterotremus 177 Paragonimus hueitungensis 177 Paragonimus kellicotti 176-7 Paragonimus mexicanus 178 Paragonimus miyazakii 178 Paragonimus peruvianis 178 Paragonimus szechuanis 178 Paragonimus tuanshahensis 177 Paragonimus westermani clinical features 171-2 diagnosis 172 differentiation 177 discovery 159-63 epidemiology 174-5 landmarks 185 life cycle 164-9 nomenclature 163 pathology 169-70 prevention 175-6 synopsis 159 treatment 172-4 Parascaris equorum 473 Parasitism 24-5 Parasitophobia 770 Paromomycin 90 Parthenogenesis 549 Paryphostomum sufratyfex 309 Pelodera strongyloides 741 . 8 Nematomorpha 2 Niclofolan 174 Niclosamide 89.see Blanfordia. 469. 282. rules of zoological 16 -24 Nomenclature 1-28. 693 Parafossarulus . 440 Papyrus Ebers 75-6. see also individual worms Notropis 144 Odontobutis 306 Oesophagostomum apiostomum 740 Oesophagostomum bifurca 740 Oesophagostomum brumpti 740 Oesophagostomum stehpanosum 740 Oleum animali Dippelis 82 Oleum cajeputi 82 Oleum chaberti 82 Oleum terebinthicae 82 Olive oil 448 Onchocerca dermathemica 662 Onchocerca gutturosa 684 Onchocerca volvulus clinical features 670-7 diagnosis 677-8 discovery 661-4 epidemiology 681-2 landmarks 691 life cycle 667-70 nomenclature 664 pathology 665-7. 426 Niridazole 89-90. 209. 711 Nomenclature. Katayama Opisthorchis felineus 306-7 843 Opisthorchis guayaquilensis 309 Opisthorchis noverca 308-9 Opisthorchis sinensis 142 Opisthorchis tenuicollis 308 Opisthorchis viverrini 308 Orientobilharzia 287 Ornithobilharzia 287 Ostertagia circumcincta 741 Ostertagia ostertagi 741 Oxamniquine 90. 355. 439. 411. 670-7 prevention 682-4 synopsis 661 treatment 679-80 Onchocerciasis 661-91 Oncomelania . 520. 253. 217. law of 18. 426 Preformation 33 Priority. 217. 289. 449 Philophthalmus 309 Phocanema 743 Physaloptera caucasica 741 Physaloptera mordens 741 Physopsis 203-4 Piperazine 87. 325 Polysarcus 163 Pomatiopis 177 Pomegranate 76. 191 epidemiology 218-9 landmarks 231 nomenclature 189-91 pathology 205-8 prevention 220-2 synopsis 187 treatment 212-8 Schistosoma incognitum 287 Schistosoma intercalatum 287 Schistosoma japonicum clinical features 279-81 diagnosis 281 discovery 263-8 epidemiology 283-4 Perca 402 Periodicity 613-5 Pernicious anaemia 407-10 Phenothiazine 87.844 A History of Human Helminthology Pyrvinium . 411. 439. 341-4. 307. 146 Pseudoparasites 770 Pseudorhabditis stercoralis 547 Pulex 422-3. 119. 412 Salpae 109 Salvarsan .see Viprynium Quinacrine . 241.see Mepacrine Raillietina celebensis 427 Raillietina demerariensis 427 Raillietina madagascariensis 426 Rats 724 Rattus 724 Redia 108 Rhabditis 502. 375. 374 Punica granatum 76. 485-6 Pygidiopsis summa 310-1 Pyrantel 90. 517. 742 Rhabdonema intestinale 14 Rhabdonema strongyloides 548 Rictularia 742 Rockefeller Foundation 222. 137. 544. 151.see Sulphonamides Pseudasbora 144. 425 Pulmonema cantonensis 723 Pumpkin seeds 80. 449. 529 -30 Royal yellow worms 107-8 Rules of zoological nomenclature 16 -24 Rundwürmer 7 Salmo 306. 374 Potadoma 177 Potamon 165-8 Praziquantel 92. 22-4 Proglottis 361 Prontosil .see Semen-contra-vermes Saugwürmer 7 Scannus 423 Scheloribates 421 Schistosoma bovis 202. 487.see Arsenicals Santonin . 287 Schistosoma cattoi 267 Schistosoma haematobium clinical features 208-11 dams and 219 diagnosis 211-2 discovery 187-9. 325 Polycephalus hominis 7. 300-1 Platyhelminthes 1 Plectoglossis 305-6 Plerocercoides prolifer 430 Polycephalus echinococcus 7. 526 Pyrgophyla 202 . 374 Punta 308 Purgatives 82. 282. 546. 486-7 Pirenella 304 Plagiorchis 309 Plagiorchis congolensis 310 Plagiorchis javensis 310 Plagiorchis muris 310 Plagiorchis philippinensis 310 Planaria latiuscula 103 Planorbarius 204 Planorbina 244 Planorbis 132. 202-4. 136. 143-7. 137 .Subject Index landmarks 295 life cycle 268-76 pathology 276-9 prevention 284-6 synopsis 263 treatment 281-2 Schistosoma mansoni clinical features 249-51 diagnosis 251-3 discovery 233-40 epidemiology 254 landmarks 262 life cycel 240-4 nomenclature 236 pathology 244-9 prevention 220-2 synopsis 187 treatment 217-8 Schistosoma margrebowiei 288 Schistosoma matthei 288 Schistosoma mekongi 288 Schistosoma rodhaini 289 Schistosome dermatitis 286-7 Schistosomes. 679 Syngamus kingi 733 Syngamus laryngeus 733 . Thiara Sesarma 166 Sheep rot 116-7. 106-14. 240-4. 270-6. 130-2. 304-5.see Antimonials Stilbazium 90 Stizolobium 82 Stizostedeon 412 Stomachida lumbricoides 470 Strobilos 361-2 Strongyloides intestinalis 15 Strongyloides stercoralis clinical features 557-9 diagnosis 559-60 discovery 543-50 epidemiology 562 landmarks 569-70 life cycle 551 nomenclature 546 pathology 550-1. 300-2. avian 286-7 Schistosomiasis haematobia 187-231 Schistosomiasis japonica Schistosomiasis mansoni 233-62 Sclerostoma caninum 722 Sclerostoma duodenale 12. 309.see Antimonials Stibophen . 730 Sparganosis 428-30 Sparganum erinacei-europaei 431 Sparganum mansoni 428 Sparganum proliferum 430 Spelotrema brevicaeca 311 845 Spirocerca lupi 742 Spirometra 430 Spirometra erinacei 431 Spirometra houghtoni 430-1 Spirometra neoplastica 776-7 Spirometrosis 430-1 Spontaneous generation 29-53 Stannum 82 Stellanctchasmus falcatus 312 Stephanolecithus parvus 168 Stibocaptate . 486 Semisulcospira . 307. 298. 119-20 Simulium 668-70 Siropotamon 177 Slugs 724 Snails .see Melania. 723 Snakes 429. 164-9. 501 Scolex 362 Segmentina 130-2.see also Planorbis Semen-contra-vermes 77. 553-7 prevention 562 synopsis 543 treatment 560-1 Strongyloidiasis 543-70 Strongylus colubriformis 746 Strongylus contortus 732 Strongylus convulutus 741 Strongylus elongatus 739 Strongylus fülleborni 562 Strongylus fülleborni-like 562 Strongylus gigas 728 Strongylus intestinalis 546 Strongylus lupi 742 Strongylus ostertagi 741 Strongylus probulurus 746 Strongylus quadridentatus 501 Strongylus subtilis 747 Sudanautes 177 Sulphonamides 173 Suramin 87. 198-205. 311.see individual genera Snails 49. 388 Taenia multiceps 332. 356-7. 422 Taenia cucurbitina grandis saginata 5. 386-7 Taenia demerariensis 427 Taenia dentata 388 Taenia echinococcus 12. 440. 525 Tetramisole 91. 362-3. 586. 431-2 Taenia murina 424 Taenia nana 12. 561. 6. 365 Taenia hydatigena granulosa 325 Taenia inerme 388 Taenia infantis 457 Taenia intestinorum 398 Taenia lata 4 Taenia longihamatus 433 Taenia madagascariensis 427 Taenia mediocanellata 12. 487. 328. 331 Taenia osculis marginalibus oppositus 422 Taenia pellucida 388 Taenia pisiformis 329 Taenia prima Plateri 398 Taenia saginata clinical features 392 diagnosis 392 discovery 385-9 epidemiology 393 landmarks 396 life cycle 389-91 . 422 Taenia cateniformis 331 Taenia cellulosae 6 Taenia crassiceps 329.846 A History of Human Helminthology nomenclature 3-4. 433 Taenia cucumerina 331. 469 Tabanids 647-9 Taenia à épine 398 Taenia alveolaris 344 Taenia brauni 431-2 Taenia canina 14. 423. 365-6 Taenia solium clinical features 369-72 diagnosis 372-3 discovery 355-63 epidemiology 376 landmarks 383 life cycle 364-9 nomenclature 3-4. 386. 18. 332. 136. 432-3 Taenia crassicollis 328-30. 727 Thiara 145-6 . 398 Taenia secunda Plateri 398 Taenia serialis 431-2 Taenia serrata 330. 5. 433 Taenia vesicularis. 364. 331-3 Taenia egyptiaca 424 Taenia elliptica 12 Taenia ex cysticerco tenuicollo 365-6 Taenia flavopunctata 12 Taenia hydatigena 320. cerebrina. 449. 526. curse of 616 Thominx aerophila 725 Thymobenzene 213 Syngenesis 33 Systema Naturae 1. multiceps 432 Taenia visceralis 6 Taenia visceralis socialis granulosus 5.see also Melania Thomas. 324.see Antimonials Tenebrio 328. 425 Ternidens deminutus 742-3 Terranova 743 Tetrachlorethylene 87. 361-2 prevention 376-7 synopsis 355 treatment 373-5 Taeniarhynchus saginata 389 Taeniasis saginata 385-396 Taeniasis solium 355-83 Taenia taeniaeformis 324. 325-6 Taenia vulgaris 6 Tanaceti vulgaris semina 82 Taphius 244 Tartar emetic . 386-7 Taenia cucurbitina plana pellucida 5. 487 Tetrapetalonema perstans 737 Tetrapetalonema streptocerca 738 Thecosema 189 Thelazia californiensis 744 Thelazia callipaeda 743 Theology 38 Thiabendazole 91. 388-9 prevention 393 synopsis 385 treatment 392 Taenia sans épine 386. 486 Tylenchus 737 Tympanotonus 304 Umbilical worms 768-9 Uncinaria americana 15Uncinaria duodenale 501 Uncinaria duodenalis 501 Uncinaria stenocephala 501-2. 744 Toxocara cati 473. 462. 457. 573 Trichinella spiralis clinical features 582-4 diagnosis 584-5 discovery 571-80 epidemiology 586-8 landmarks 596 life cycle 578-80 nomenclature 573 pathology 580-2 prevention 588-91 synopsis 571 treatment 585-6 Trichinosis 571-96 Trichobilharzia 286 Trichocephalos 5 Trichocephalus affinis 458 Trichocephalus crenatus 458 Trichocephalus depressiusculus 458-9 Trichocephalus dispar 11. 8-9 Trichina affinis 10. 579 Trichocephalus hominis 6 Trichocephalus trichiurus 15 Trichodectes 422 Trichosoma aerophilum 725 847 Trichosoma cutaneum 721 Trichostrongyliasis 746-7 Trichostronyglus axei 746 Trichostrongylus brevis 746 Trichostrongylus colubriformis 746 Trichostrongylus orientalis 746 Trichostrongylus skrjabini 746 Trichostrongylus vitrinus 746 Trichuriasis 455-68 Trichuris suis 463 Trichuris trichiura clinical features 459-61 diagnosis 461-2 discovery 455-7 epidemiology 463 landmarks 468 life cycle 457-8 nomenclature 456-7 pathology 458-9 prevention 463 synopsis 455 treatment 462 Trichuris vulgaris 457 Trichuris vulpis 463-4 Tricula 177-8. 448. 746 Toxocariasis 744-6 Transmission of worms 29-74 early times 29-33 1650-1699 33-7 1700-1749 37-9 1750-1799 39-41 1800-1824 41-3 1825-1849 43-6 1850-1874 46-53 1875-1899 53-5 1900-1924 55-8 1925+ 68-9 landmarks 70-3 see also Individual worms Trapa 132 Treatment. 747 Unio 193 Univocal generation 36 Unorthodox treatment 772-3 . 374 Tinca 307 Toothworms 765-8 Toxocara canis 473. 288 Troglotrema salmincola 311 Tropical eosinophilia 629-30 Tropicorbis 243 Turpentine 374.Subject Index Tilapia 304 Tin 78. unorthodox 772-3 Treatment. worms as 774 Trematoda 1. 457 Trichina spiralis 10. 4 Viprynium 92. 425 Zebrina 298 Zoological nomenclature 16-24 Zoophyta 4 Water caltrop 132.see Oil of Chenopodium Wuchereria bancrofti clinical features 615-23 diagnosis 623-4 discovery 597-605 . 136-7 Water chestnut 132. 136-7 Watercress 120 Watsonius watsoni 311-2 Worm. 449 Vitamin B12 409-10 A History of Human Helminthology epidemiology 626-7 landmarks 640 life cycle 606-13 nomenclature 604 pathology 618-23 periodicity 613-5 prevention 627-8 synopsis 597 treatment 624-6 Wuchereria malayi 605 Wuchereria pahangi 605 Xenopsylla 423. derivation of term 1 Wormseed oil .848 Urine worms 768 Vermes 1 Verminus 777 Vermis 1.
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