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Principles and Practice of Clinical Parasitology. Edited by S. Gillespie & Richard D. Pearson Copyright © 2001 John Wiley & Sons Ltd

Principles and Practice of Clinical Parasitology

Edited by

Stephen H. Gillespie Royal Free Hospital and School of Medicine and Richard D. Pearson University of Virginia Health Sciences Center, Charlottesville, Virginia, USA

JOHN WILEY & SONS, LTD

Chi c hest er• New Y ork• Weinheim• B r i sbane• Singapore• Toron t o

Principles and Practice of Clinical Parasitology. Edited by S. Gillespie & Richard D. Pearson Copyright © 2001 John Wiley & Sons Ltd

Principles and Practice of Clinical Parasitology

Principles and Practice of Clinical Parasitology. Edited by S. Gillespie & Richard D. Pearson Copyright © 2001 John Wiley & Sons Ltd

Principles and Practice of Clinical Parasitology

Edited by

Stephen H. Gillespie Royal Free Hospital and School of Medicine and Richard D. Pearson University of Virginia Health Sciences Center, Charlottesville, Virginia, USA

JOHN WILEY & SONS, LTD

Chi c hest er• New Y ork• Weinheim• B r i sbane• Singapore• Toron t o Principles and Practice of Clinical Parasitology. Edited by S. Gillespie & Richard D. Pearson Copyright © 2001 John Wiley & Sons Ltd

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Library of Congress Cataloging-in-Publication Data

Principles and practice of clinical parasitology / edited by Stephen Gillespie, Richard D. Pearson. p. cm. Includes bibliographical references and index. ISBN 0-471-97729-2 (cased) 1. Medical parasitology. I. Gillespie, S. H. II. Pearson, Richard D.

QR251 .P775 2001 616.9' 6—dc21 00-047755

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A catalogue record for this book is available from the British Library

ISBN 0-471-97729-2

Typeset in 10/12pt Times from authors’ disks by Dobbie Typesetting Limited, Tavistock, Devon Printed and bound in Great Britain by Antony Rowe Ltd, Chippenham, Wiltshire This book is printed on acid-free paper responsibly manufactured from sustainable forestry, in which at least two trees are planted for each one used for paper production. Principles and Practice of Clinical Parasitology. Edited by S. Gillespie & Richard D. Pearson Copyright © 2001 John Wiley & Sons Ltd

Contents

List of Contributors vii 12 Pathogenic and Opportunistic Free-living Amebas: Naegleria fowleri, Preface ix Acanthamoeba spp. and Balamuthia mandrillaris 269 1 History of Parasitology 1 Augusto Julio M artı´nez and G. C. Cook Govinda S. Visvesvara

2 Parasite Epidemiology 21 13 Leishmaniasis 287 D. A. P. Bundy and E. M ichael Richard D. Pearson, Selma M . B. Jeronimo and 3 Malaria 53 Anastacio de Q. Sousa B.-A. Biggs and G. V. Brown 14a African Trypanosomiasis 315 4 Babesiosis 99 I. Balakrishnan and A. Z umla Jeffrey A. Gelfand and Debra D. Poutsiaka 14b American Trypanosomiasis (Chagas’ Disease) 335 5 Toxoplasmosis 113 Louis V. Kirchhoff Joseph D. Schwartzman 15 Blastocystis 355 6 Cryptosporidiosis and Isosporiasis 139 D. J. Stenzel and R. E. Boreham Cynthia L. Sears and Beth D. Kirkpatrick 16 Schistosomiasis 369 G. Richard Olds and 7 Cyclospora 165 Srinivasan Dasarathy Richard L. Guerrant and Theodore S. Steiner 17 Hepatobiliary and Pulmonary Flukes: Opisthorchis, Clonorchis, Fasciola and 8 Microsporidia 171 Paragonimus Species 407 E. U. Canning Thomas R. Hawn and Elaine C. Jong

9 Amebas 197 18a Blood-borne Filarial Infections: Upinder Singh and W illiam A. Petri Jr , , , , Mansonella 10 Giardia lamblia 219 perstans and Mansonella ozzardi 433 David R. Hill Thomas B. Nutman

11 Trichomonads 243 18b Onchocerciasis 457 J. P. Ackers J. Whitworth vi CONTENTS

18c Strongyloides stercoralis 21 Intestinal 561 and S. fulleborni 479 Stephen H. Gillespie John F. Lindo and M ichael G. Lee 22 Echinococcosis 585 19a Toxocariasis 501 R. C. A. Thompson M . R. H. Taylor and Celia V. Holland

19b Trichinellosis 521 23 Cestodes 613 Peter M . Schantz and Vance Dietz Kaethe W illms and Julio Sotelo

19c Migrating Worms 535 24 Intestinal Trematodes 635 Stephen H. Gillespie Thomas R. Hawn and Elaine C. Jong 20 Dracunculiasis 553 Ralph M uller Index 647 Principles and Practice of Clinical Parasitology. Edited by S. Gillespie & Richard D. Pearson Copyright © 2001 John Wiley & Sons Ltd

Contributors

J. P. Ackers Department of Infections and Jeffrey A. Gelfand International M edical Affairs Tropical Diseases, London School of Hygiene Partners, Healthcare System, M assachusetts and Tropical M edicine, Keppel Street, London General Hospital, 50 Stanford Street, Suite 801, W C1E 7HT, UK Boston, MA 02114-2517, USA S. I. Balakrishnan Department of M edical Stephen H. Gillespie Department of M edical M icrobiology, Royal Free & University College M icrobiology, Royal Free and University College M edical School, Rowland Hill Street, London Hospital M edical School, Pond Street, London NW3 2PF, UK NW3 2QG, UK B.-A. Biggs Division of Infectious Diseases, Richard L. Guerrant Division of Geographic and Department of M edicine, The W alter and Eliza International M edicine, Box 801379, University of Hall Institute of M edical Research, Royal Virginia School of M edicine, Charlottesville, VA M elbourne Hospital, Victoria 3050, Australia 22908, USA R. E. Boreham PO Box 1246, Toowong, Thomas R. Hawn Division of Allergy and Queensland 4066, Australia Infectious Diseases, Department of M edicine, University of W ashington M edical Center, The Graham Brown Division of Infectious Diseases, Institute for Systems Biology, Suite 200, 4225 Department of M edicine, The W alter and Eliza Roosevelt W ay NE, Seattle, W A 98105, USA Hall Institute of M edical Research, Royal David R. Hill Division of Infectious Diseases, M elbourne Hospital, Victoria 3050, Australia University of Connecticut Health Center, Farm- D. A. P. Bundy The W orld Bank, 1818 H. Street ington, CT 06030-3212, USA NW , W ashington, DC 20433, USA Celia V. Holland Department of Z oology, E. Canning Department of Biology, Imperial Trinity College, Dublin 2, Ireland College of Science, Technology and M edicine, Selma M. B. Jeronimo Department of Biochem- London SW 7 2AZ , UK istry, Universidade Federal do Rio Grande do Norte, G. C. Cook The W ellcome Trust Centre for the Natal, Brazil History of M edicine at UCL, 183 Euston Road, Elaine C. Jong University of W ashington, Hall London NW 1 2BE, UK Health Primary Care Center, Box 354410, Seattle, W A 98195-4410, USA Srinivasan Dasarathy M etroHealth M edical Center, Case W estern Reserve University, 2500 Michael G. Lee Department of M edicine, Uni- M etroHealth Drive, Cleveland OH 44109-1998, versity of the W est Indies, M ona, Kingston 7, USA Jamaica Vance Dietz Organizacio´n Panamericana de Louis V. Kirchhoff University of Iowa, Depart- Salud, M arcelo T. de Alvear 684, 4 Piso, 1395 ment of Internal M edicine, 300G EM RB, Iowa Buenos Aires, Argentina City, IA 52242, USA viii CONTRIBUTORS

Beth D. Kirkpatrick Division of Infectious Cynthia L. Sears Department of M edicine, Diseases, Department of M edicine, University of Division of Infectious Diseases and Gastroenterol- Vermont School of M edicine, Burlington, VT, USA ogy, Johns Hopkins University School of M edicine, Baltimore, M D 21205, USA John F. Lindo Department of M icrobiology, University of the W est Indies, M ona, Kingston 7, Upinder Singh University of Viginia School of Jamaica M edicine, 300 Park Place, Charlottesville, VA Augusto Julio Martı´nez University of Pittsburgh 22908, USA School of M edicine, Department of Pathology, Anastacio de Q. Sousa Department of Internal Division of Neuropathology, 200 Lothrop Street, M edicine, Universidade Federal do Ceata, Forta- Pittsburgh, PA 15213-2582, USA leza, Brazil E. Michael Department of Infectious Disease Julio Sotelo Instituto Nacional de Neurologı´ay Epidemiology, Imperial College School of M edi- Neurocirugı´a, Insurgentes Sur 3877, M exico City cine, Norfolk Place, London W 2 1PG, UK 14269, M exico Ralph Muller International Institute of Parasi- Theodore S. Steiner Division of Geographic and tology, 22 Cranbrook Drive, St Albans, International M edicine, Box 801379, University of Hertfordshire AL4 0SS, UK Virginia School of M edicine, Charlottesville, VA Thomas B. Nutman Helminth Immunology 22908, USA Section and Clinical Parasitology Unit, Lab- D. J. Stenzel Analytical Electron M icroscopy oratory of Parasitic Diseases, National Institute Facility, Queensland University of Technology, of Allergy and Infectious Diseases, National Garden Point Campus, 2 George Street, GPO Box Institutes of Health, Building 4, Room B1-03, 2434, Brisbane, Queensland 4001, Australia Bethesda, M D 20892-0425, USA M. R. H. Taylor Department of Paediatrics, G. Richard Olds M edical College of W isconsin, Trinity College, Dublin 2, and National Children’s Department of M edicine, 9200 W . W isconsin Hospital, Harcourt Street, Dublin 2, Ireland Avenue, Suite 4186, M ilwaukee, W I 53226, USA Richard D. Pearson University of Virginia R. C. A. Thompson Department of Veterinary School of M edicine, Department of M edicine & Studies, M urdoch University, M urdoch, W A 6150, Pathology, Box 801379, Charlottesville, VA 22908, Australia USA J. Whitworth MedicalResearchCouncil,Uganda William A. Petri Jr University of Virginia Virus Research Institute, PO Box 49, Entebbe, Health Sciences Center, 300 Park Place, M R4 Uganda Building, Room 2115, Charlottesville, VA 22908, Kaethe Willms Department of M icrobiology and USA Parasitology, Facultad de M edicine, Universidad Debra D. Poutsiaka New England M edical Nacional Auto´noma de M e´xico, M exico City, Center, 750 W ashington Street, Boston, M A Mexico 02111, USA Govinda S. Visvesvara Division of Parasitic Peter M. Schantz Division of Parasitic Diseases, Diseases, National Center for Infectious Diseases, National Center for Infectious Diseases, Centers Centers for Disease Control and Prevention, for Disease Control and Prevention, 4770 Buford Atlanta, GA 30333, USA Highway, Atlanta, GA 30341-3724, USA A. Zumla Centre for Infectious Diseases, Uni- Joseph D. Schwartzman Department of Pathol- versity College London, Royal Free and University ogy, Dartmouth-Hitchcock M edical Center, 1 College M edical School, Rowland Hill Street, M edical Center Drive, Lebanon, NH 03756, USA London NW 3 2PF, UK Principles and Practice of Clinical Parasitology. Edited by S. Gillespie & Richard D. Pearson Copyright © 2001 John Wiley & Sons Ltd

Preface

In the 1970s and 1980s, in an attempt to focus Globalisation has changed the spectrum of world attention on parasitic diseases, the World parasitic infection in clinical medical practice. Health Organization formed the Tropical Dis- Not only has the incidence of disease world- eases Research Group. Their target was six major wide risen, but frequency of travel, migration infections that damaged the health of individuals and population dispersal due to war has in developing countries, and five of these six were resulted in individuals presenting with parasitic parasitic diseases. The Rockefeller Foundation infections in locations where these diseases also identified parasitic infections as a major have become rare. Patients with malaria and target for health improvement for the world intestinal protozoan and helminth infections community. They formed a research network to are now an everyday occurrence in family develop new drugs and vaccines by understand- practice throughout the world. The diagnosis ing the pathogenesis of diseases. Its title ‘The of parasitic diseases has also become an every- Great Neglected Diseases Network’ emphasised day component of medical laboratory practice that, in the post-colonial world, parasitic diseases worldwide. were no longer identified by governments and The HIV pandemic has also had a potent pharmaceutical companies as important subjects influence on the spectrum of parasitic infections. for medical research. Despite the success of these A number of organisms that cause disease rarely two ventures in developing our understanding of have become commonplace. The HIV epidemic the immunology, molecular biology and poten- itself was identified through an apparent epi- tial for vaccines and drugs, the position of demic of Pneumocystis carinii infection, at that parasitic diseases in the world is, if anything, time considered to be a protozoan and now worse than it was 30 years ago. The territories in considered to be a fungus. Intractable crypto- which malaria is endemic have expanded and the sporidiosis and isosporiasis, and the recognition number of cases with it. Malaria causes more of microsporidium infections and cerebral toxo- than a million child deaths in Africa every year. plasmosis, have all been consequences of severe The number of individuals suffering from intest- immunocompromise secondary to HIV infection. inal helminth infections has more than doubled Visceral leishmaniasis, too, has been recognised in the last 50 years and the prevalence of as a major opportunistic disease in HIV-infected schistosomiasis is rising. Urbanisation in Brazil, individuals in Southern France and Italy. where more than 80% of the population live in New technologies have increased our ability to cities, has resulted in large peri-urban epidemics investigate parasitic diseases and to understand of Chagas’ disease and epidemics of visceral the biology of the organisms and the hosts’ leishmaniasis. This general global deterioration immune response to them. Developments in has occurred in a context where, for many immunology and molecular biology have enabled countries, endemic parasitic diseases are a thing diagnostic laboratories to improve the diagnosis of the past. In epidemiological terms, parasitic of parasitic infections through enzyme-immu- infections are over-dispersed or, in more every- noassays and DNA amplification techniques. day terms, focused in the poorest sector of the Genome sequence programmes are under way world community. for parasites, including malaria, Leishmania and x PREFACE amoebas and these may lead to the identification parasitic infections in medical practice. The of new virulence determinants, or targets for editors hope that those who read and use this chemotherapy or vaccine development. Although book will develop their clinical diagnostic and new treatments and vaccines have progressed therapeutic skills, and that these skills will be more slowly than in other infection disciplines, used for the benefit of those who most need effective chemotherapy is now available for them—the people who are often the poorest in almost all parasitic infections. the world community. An international panel of authors have drawn together their experience and understanding of parasitic infections. The chapters contain a Stephen H. Gillespie clinically orientated overview of all the major Richard D. Pearson Principles and Practice of Clinical Parasitology. Edited by S. Gillespie & Richard D. Pearson Copyright © 2001 John Wiley & Sons Ltd 1

History of Parasitology

G. C. Cook The W ellcome Trust Centre for the History of M edicine at UCL, London, UK

INTRODUCTION by Anthony Fitzherbert (1470–1538) in ANewe Treate or Treatyse most Profytable for All Husbandemen in 1532. Many of the larger helminths (e.g. Ascaris Helminths were in some cases considered to lumbricoides, Dracunculus medinensis and Taenia improve the health of an infected individual spp.) and ectoparasites must have been visualised (Foster, 1965); the ancient Chinese, for example, in ancient times (Foster, 1965)—in fact, since Homo believed that a man should harbour at least three sapiens first became aware of his immediate worms to remain in good health, and in eight- environment. D. medinensis was certainly recog- eenth century Europe many regarded the nised on the shores of the Red Sea in the pre- presence of ‘worms’ in children as being bene- Christian era. The first clear documentation of ficial to their health. By contrast, there were these organisms is to be found in the Papyrus reports of fanciful or imaginary worms causing Ebers (c. 1550 BC) and other ancient Egyptian all manner of disease(s); parasites were in fact writings (Nunn, 1996); these writers were also implicated in the seventeenth century in the aware of Schistosoma spp., which remain to this aetiology of many diseases, including syphilis day a major scourge of that country. Aristotle and plague. was familiar with helminths involving dogs, fish, and pigs (Cysticercus cellulosae) (Foster, 1965); the presence of this latter helminth in the tongues of pigs is alluded to in a comedy (The Knights)by The Doctrine of ‘Spontaneous Generation’ Aristophanes. Galen (AD 131–199) recognised three human (macro)parasites: A. lumbricoides, From ancient times until the mid-nineteenth Taenia spp. and Enterobius vermicularis. century, there was a widespread belief that Aretaeus the Cappodocian (AD 81–138) was parasites arose by ‘spontaneous generation’— apparently familiar with human hydatidosis. either on or in the human body (Foster, 1965), The Arabs seem to have added little (if that was part of a much broader hypothesis anything) of importance to existing knowledge which held that all living things arose in this of human parasitoses; they, too, were familiar manner. In the seventeenth century, William with D. medinensis. A twelfth century nun, Harvey (1578–1657) cast doubt on this doctrine Hildegardis de Pinguia, recognised the ecto- and Jan Swammerdam (1637–1680) was firmly parasite (a mite) causing scabies (Foster, 1965). of the opinion that it did not occur. Antony The first fluke to be well documented was van Leeuwenhoek (1632–1723) did not consider Fasciola hepatica; this was accurately described that weevils spontaneously generate in corn

Principles and Practice of Clinical Parasitology Edited by Stephen Gillespie and Richard D. Pearson © 2001 John Wiley & Sons Ltd 2 PRINCIPLES AND PRACTICE OF CLINICAL PARASITOLOGY seed, and Francesco Redi (1626–1697) dis- worm—Taenia saginata. He also associated proved the widely-held contemporary view worms with venereal disease(s) but apparently that flies arise spontaneously from meat. By doubted a cause–effect relationship (Foster, carrying out careful dissections of A. lumbri- 1965). Andre´ considered that predisposing fac- coides, Edward Tyson (1650–1708) showed tors (to infection) were bad air and bad food there were two sexes and that in fact they (both of which contained ‘seeds of worms’) and multiplied by sexual reproduction; like most overindulgence in food. contemporaries, however, he believed that the One of the most influential figures in eight- original parasites arose by ‘spontaneous gen- eenth century parasitology was Pierre Pallas eration’. Georges Leclerc, Comte de Button (1741–1811), whose other major interest was (1717–1788) and Albrecht von Haller (1708– exploration (of the Russian Empire) (Foster, 1777) undoubtedly believed in ‘spontaneous 1965); after graduation at Leyden in 1760, he generation’ and, as late as 1839, the anatomist wrote a thesis, De infestis viventibus intraviventia. Allen Thompson (Foster, 1965) wrote that this He also wrote a zoological text, M iscellanea form of generation was ‘to be looked upon as zoologica, in which he concentrated on bladder no more than an exception to the general law worms—all of which, he considered, belonged to of reproduction . . .’. Two distinguished a single species, Taenia hydatigena. parasitologists of the later eighteenth cen- Go¨ze (see above), an amateur naturalist, tury—Marcus Bloch (1723–1799) and Johan made several important contributions to hel- Go¨ze (1731–1793) (see below)—both believed minthology; his monumental Versuch einer that parasites were ‘inborn’ in their hosts. V. L. Naturgeschichte der Eingeweidewu¨rmer tierischer Brera (1772–1840), professor of medicine at Ko¨rper was published in 1787. He discovered Pavia, wrote in 1798 that he was opposed to the scolex of Echinococcus spp. in hydatid the idea of spontaneous generation; although cysts. Bloch (a doctor of medicine in Berlin) (see believing that worms develop from eggs above), whose prize-winning essay Abhandlung ingested with food, he considered that this von der Erzeugung der Eingeweidewu¨rmer was occurs only in individuals whose constitution is published in 1782, was the first to draw attention favourable to the worm, i.e. that a ‘host-factor’ to the hooklets on the head of the tapeworm. has a significant role in the parasite–host equation. The ‘doctrine of spontaneous genera- tion of parasites’ was not finally abandoned until late in the nineteenth century (Foster, The Nineteenth Century 1965). This century saw several important texts on helminthology. Brera (see above) (at Pavia, where he had access to Go¨ze’s fine collection of ORIGINS OF THE helminths) poured scorn on the idea that the SPECIALITY—PARASITOLOGY presence of worms was either necessary for, or contributed to, health. However, like others The Italian, Redi (see above) has perhaps the best before him, he confused the two species of claim to the title, ‘father of parasitology’: he human tapeworm—Taenia solium and T. saginata. wrote Osservazioni intorni agli animali viventi che Despite Brera’s contributions, Carl Rudolphi si trovano negli animali viventi, and was especially (1771–1832), the foremost parasitologist of his interested in ectoparasites (Foster, 1965), parti- day, contributed the most important parasitolo- cularly lice, although in his classical text he also gical work of the early nineteenth century. He described dog and cat tapeworms, and had in utilised the microscope for histological studies, 1671 produced an illustration of Fasciola and his scholarly two-volume work Entozoorum hepatica. Another early text was that due to sive vermium intestinalium historia naturalis Nicolas Andre´ (1658–1742), De la ge´ne´ration des (1808), together with Entozoorum synopsis cui vers dans le corps de l’homme (1699); he was the accedunt mantissa duplex et indices locupletissima first to illustrate the scolex of a human tape- (1819), substantially increased the list of known HISTORY 3 parasites. Other important texts about this time fluke—thus illustrating his hypothesis of the were due to J. S. Olombel (Foster, 1965) in 1816, ‘alternation of generations’. and Johann Bremser (1767–1827) in 1819. Another parasitologist of distinction in the early nineteenth century was Fe´lix Dujardin Emergence of Thomas Spencer Cobbold (1801–1860); in 1840 he was appointed to the (1828–1886) chair of zoology at Rennes, and was the first worker to appreciate that trematodes and ces- Until the 1860s, parasitology was virtually todes pass part of their life-cycle in an neglected in Britain; during his lifetime, Cobbold intermediate host, and that ‘bladder worms’ are became the major British authority on the subject. part of the life-cycle of tapeworms; these The son of a Suffolk clergyman (Anonymous, observations were regrettably not published. He 1886), he served an apprenticeship with a also introduced the term ‘proglottis’ (a segment Norwich surgeon, J. G. Crosse; after a few of the tapeworm). His major parasitological text months of postgraduate study in Paris, he was Histoire naturelle des helminthes ou vers returned to the anatomy department of John intestinaux (1845). Goodsir at Edinburgh, where he studied com- parative anatomy, and observed many parasites, including Fasciola gigantica in the giraffe. In 1857, he obtained the post of Lecturer in Botany at St Mary’s Hospital, London and in Early English Texts on Parasitology 1861 he was appointed to a lectureship at the Middlesex Hospital; in 1864 he was elected FRS, At the outset of the nineteenth century there was and in 1873 he obtained the post of professor of virtually nothing written on this subject in botany and helminthology at the Royal Veter- English, nearly all work emanating from main- inary College, London. In 1864, he published land Europe. Matthew Baillie (1761–1823) had Entozoa, an Introduction to the Study of included relevant passages in M orbid Anatomy of Helminthology; this book and its successor Some of the M ost Important Parts of the Human (Figure 1.2) contained a detailed account of all Body (1793); he noted that tapeworm infections the (known) parasites to affect Homo sapiens. were uncommon in Britain (Foster, 1965). In the Following publication of this text (which had 1840s several continental works on helminthol- many enthusiastic reviews), Cobbold set up as a ogy were translated into English, most by George physician with a specialist interest in parasitic Busk FRS (1807–1886) Surgeon to The Seamen’s disease. Due to his, by then, worldwide reputa- Hospital Society (Cook, 1997a) and issued by the tion, he presented, on behalf of Patrick Manson Ray Society; in 1857, the Sydenham Society (1844–1922; Figure 1.3) the discovery of the published two volumes which contained transla- development of ‘embryo’ filariae (microfilariae) tions of M anual of Animal and Vegetable in the body of the mosquito, to the Linnean Parasites (by Gottleib Ku¨chenmeister, 1821– Society of London on 7 March 1878. In 1879 he 1890), and Tape and Cystic W orms (by Carl published Parasites: a Treatise on the Entozoa of von Siebold, 1804–1885). However, the Ray M an and including Some Account of the Society had already published On the Alternation Ectozoa. of Generations; or, the Propagation and Develop- ment of Animals through Alternate Generations (1845) (Figure 1.1) by the Danish naturalist Johannes Steenstrup (1813–1897); in Chapter 4 Other European Contributions in the of this seminal text he described cercariae Nineteenth Century (liberated by fresh-water molluscs) which remained encysted for several months and con- A French parasitologist (primarily a general tained the parasitic fluke Distoma. Steenstrup practitioner), who is now largely forgotten, was had therefore elucidated, and published, the Casimir Davaine (1812–1882); he wrote extensively complete life-cycle of one species of liver on anthrax—before Robert Koch (1843–1910) and