Worms and Human Disease

2nd Edition Ralph Muller, DSc, PhD, FIBiol Department of Infectious and Tropical Diseases London School of Hygiene and Tropical Medicine University of London, UK and Former Director International Institute of Parasitology St Albans, Hertfordshire, UK With contributions and the chapter on Immunology of Helminths from Derek Wakelin, DSc, PhD, FRCPath School of Life and Environmental Sciences University of Nottingham, UK CABI Publishing site: www.cabi-publishing.org CAB International 2002. All rights reserved. No part of thispublication may be reproduced in any form or by any means,electronically, mechanically, by photocopying, recording orotherwise, without prior permission of the copyright owners.A catalogue record for this book is available from the BritishLibrary, London, UK. Library of Congress Cataloging-in-Publication Data Muller, Ralph, 1933-Worms and human disease / Ralph Muller ; with contributions and the chapter onimmunology from Derek Wakelin.-- 2nd ed.p. ; cm.Rev. ed. of: Worms and disease / Ralph Muller. c1975.Includes bibliographical references and index.ISBN 0-85199-516-0 (pbk.)1. Medical helminthology. 2. Helminthiasis. I. Wakelin, Derek. II. Muller, Ralph,1933- Worms and disease. III. Title.[DNLM: 1. Helminths--pathogenicity. 2. Helminthiasis. QX 200 M958w 2001]RC119.7 .M84 20012001025591ISBN 0 85199 516 0Typeset in Melior by Columns Design Ltd, Reading.Printed and bound in the UK by Biddles Ltd, Guildford and Kings Lynn.

Contents
Acknowledgements ix Introduction 1

1. The Trematodes 3
Morphology 5 Life Cycle Stages6 Classication6 Family Schistosomatidae 9 Schistosomes 9 Family Paragonimidae 32 Paragonimus westermani 32 Family Achillurbainiidae 37 Family Opisthorchidae 38 Clonorchis sinensis 38 Opisthorchis viverrini 43 Opisthorchis felineus 44 Family Dicrocoeliidae 45 Dicrocoelium dendriticum 45 Family Fasciolidae 46 Fasciola hepatica 46 Fasciolopsis buski 49 Family Heterophyidae 51 Heterophyes heterophyes 51 Metagonimus yokogawai 53 Family Paramphistomidae 55 Gastrodiscoides hominis 55 Family Echinostomidae 56 Echinostoma ilocanum 56 Other Echinostomids 56 Other Occasional and Rare Human-parasitic Trematodes 58 Family Diplostomidae 58 Family Lecithodendriidae 58 Family Plagiorchiidae 58 Family Troglotrematidae 58 Other families 59 1

2.The Cestodes 63
Classication 64 Order Pseudophyllidea 65 Diphyllobothrium latum 65 Sparganosis 70 Order Cyclophyllidea 71 Family Taeniidae 71 Taenia saginata 71 Taenia solium 76 Cysticercosis 80 Taenia multiceps 83 Echinococcus granulosus 85 Echinococcus multilocularis 94 Echinococcus oligarthrus 97 Echinococcus vogeli 97 Family Hymenolepididae 98 Hymenolepis nana 98 Hymenolepis diminuta 101 Family Dipylididae 102 Dipylidium caninum 102 Very occasional human tapeworms102 3.The Acanthocephala 106 Moniliformis moniliformis 106 Macranthorhynchus hirudinaceus 107 4.The Nematomorpha 108 5.The Nematodes 109 Classication 109 A Key to Nematodes Parasitic in Humans 113 Intestinal Nematodes 115 Geohelminths 115 Order Rhabditida 115 Family Strongyloididae 115 Strongyloides stercoralis 115 Order Strongylida 126 Family Ancylostomatidae 126 Necator americanus 126 Ancylostoma duodenale 134 Other Strongyles137 Family Trichostrongylidae 138 Trichostrongylus spp. 138 Family Chabertiidae 139 Ternidens deminutus 139 Oesophagostomum bifurcum 140 Family Syngamidae 142 Mammomonogamus laryngeus 142 Family Angiostrongylidae 143 Parastrongylus cantonensis 143 Parastrongylus costaricensis 145 vi

Contents vii Order Ascaridida 147 Family Ascarididae 147 Ascaris lumbricoides 147 Lagochilascaris minor 153 Baylisascaris procyonis 153 Family Anisakidae 154 Anisakis and other anisakids154 Larva Migrans 156 Visceral larva migrans 156 Toxocara and Toxascaris 156 Cutaneous marva migrans or creeping eruption 159 Order Oxyurida 160 Family Oxyuridae 160 Enterobius vermicularis 160 Order Enoplida 164 Family Trichuridae 164 Trichuris trichiura 164 Tissue Nematodes 173 Order Enoplida 173 Family Trichuridae 173 Aonchotheca philippinensis 173 Calodium hepaticum 175 Eucoleus aerophilus 175 Family Trichinellidae 176 Trichinella spiralis 176 Family Dioctophymidae 184 Dioctophyma renale 184 Superfamily Mermithoidea 184 Order Spirurida 184 Superfamily Gnathostomoidea 184 Gnathostoma spinigerum 184 Other Spirurids 187 Superfamily Filarioidea: the Filariae 188 Wuchereria bancrofti 190 Brugia malayi 202 Loa loa 206 Onchocerca volvulus 211 Mansonella perstans 221 Mansonella streptocerca 223 Mansonella ozzardi 225 Accidental larial infections 226 Superfamily Dracunculoidea 228 Dracunculus medinensis 228 6.Other (Non-helminth) Groups 240 Pentastomes 240 Armillifer ( = Porocephalus) Armillata 240 Linguatula serrata 240 Leeches 241 Myiasis 241

7. Immunology of Helminths 243 8. Epidemiological Aspects of Helminth Infections 252 9. Helminthological Techniques 255 Appendix 1 Summary of Some Landmarks in Medical Helminthology271 Appendix 2 Glossary of Helminthological Terms 273 Appendix 3 Location of Helminths in the Human Body 279 General References and Further Reading 282 Index 287 viii Contents

intestinal nematodes are considered in thesame section so that the new global mea-sures being advocated for all the geo-helminths can be considered together, eventhough they are not all closely related.Most of the gures for infection rateshave been obtained from the CDROMPARASITE database produced by CAB International or from MEDLINE. Mapshave concentrated principally on helminthinfections that have a focal distribution.The term helminth (Greek ) meansworm, although it is usually restricted tothe parasitic worms. The term does notrefer to any one zoological taxon but thosemembers parasitic in humans belongalmost entirely to two main groups; thephylum Platyhelminthes, which includesthe trematodes (ukes) and the cestodes(tapeworms), and the phylum Nematoda,comprising the nematodes (roundworms).This book provides a comprehensiveaccount of all important helminths foundin humans, with a mention of all othersreported, however occasionally (a total of 267 species), and includes a brief consideration of other metazoan parasites some-times found in humans, such as thepentastomids, dipteran y larvae andleeches, which may be confused with thetrue helminths. While the title is Worms and Human Disease , it must not be assumed that helminth infection invariably results indisease; most of the helminths that are pre-dominantly human parasites are patho-genic only when worm burdens are highand, as there is no multiplication withinthe body, light infections become clinicallyimportant only following reinfection. Themajority of helminth infections are lightand cause little morbidity (although insome cases more than was previouslythought), but many are so widespread thatthe low percentage of patients who suffersevere clinical disease represents a prob-lem of great medical and economicimportance. 2 Introduction Adult trematodes, or ukes, may be foundin the intestinal tract, bile-ducts, lungs or blood of humans. Some details concerningthe medically most important species areshown in Table 1. All the trematodes men-tioned in the table are normal human para-sites, except some species of Paragonimus and Fasciola and some heterophyids andechinostomes, which are accidental para-sites with humans not being involved intheir transmission cycles. However, almostall trematodes are very catholic in theirchoice of denitive hosts (a notable excep-tion is Schistosoma haematobium) and have a wide range of animal reservoirs; 144 species that have been found in humans are mentioned in the text, most of whichare natural animal parasites. Not shown inthe table are various aberrant forms, suchas the cercarial larvae of animal and birdschistosomes, which can penetrate the skinof humans but are not able to mature.Preeminent in medical and economicimportance are the schistosomes, or bloodukes, which are the cause of one of themajor human diseases, schistosomiasis.This is a source of suffering in 4

many warmcountries and is a major cause of morbid-ity. No other trematode is the cause of suchwidespread morbidity, but liver ukes(Clonorchis and the closely related Opisthorchis) and lung ukes (Paragonimus) are important parasites in areas of Asia andtheir presence may result in severe diseaseand possibly death.It needs to be stressed that the presenceof trematode parasites in the body is by nomeans synonymous with the presence of disease. In contrast to viruses, bacteria orprotozoans, trematodes do not multiplywithin the human body and the few organ-isms present in the great majority of infected persons are tolerated with theminimum of inconvenience and are oftennot diagnosed. It is the small percentage of patients with large worm burdens (so-called wormy people) or in whom the par-asites or their eggs are in ectopic sites inthe body who give cause for alarm.The digenetic trematodes are membersof the phylum Platyhelminthes, which alsoincludes the cestodes (tapeworms), mono-geneans (ectoparasites of shes andamphibians) and free-living turbellarians(planarians, etc.). Platyhelminthes, or at-worms, are acoelomate bilateria (bilaterallysymmetrical and lacking a coelom). Theexcretory system is based on the ame cell,or protonephridium, and often the patternof ame cells can be of importance in clas-sication. Trematodes are characteristicallyat and leaike, or occasionally globular,hermaphroditic organisms (except for the schistosomes, which have a male foldedabout its long axis and a cylindrical female(Figs 3 and 4)). All have complicated lifecycles with alternating sexual and asexualdevelopment in different hosts. Asexualmultiplication takes place in a snail, andfor parasites of medical importance this isalways a gastropod snail. It is believed thatthe trematodes were originally parasites of molluscs and they are still always veryspecic in their choice of snail host; 1 The Trematodes 3 4 C h a p t er 1 Table 1. Trematodes of medical importance.Situation ofEggs recovered Snail intermediate Other intermediateGeographicalHabitatSpeciesadultfromhostor transport hostsdistribution Blood Schistosoma Mesenteric veinsFaeces Biomphalaria spp.None (active penetrationAfrica, South America mansoni by cercariae) S. japonicum Mesenteric veinsFaeces Oncomelania spp.None (active penetrationChina, South-East Asiaby cercariae) S. mekongi Mesenteric veinsFaeces Neotricula None (active penetrationCambodia, Laosby cercariae) S. intercalatum Mesenteric veinsFaeces Bulinus spp.None (active penetrationCentral Africaby cercariae) S. haematobium Vesicular veinsUrine Bulinus spp.None (active penetrationAfrica, Middle Eastby cercariae)Lungs Paragonimus Cysts in lungs Sputum and faeces Semisulcospirura Edible crustaceansSouth-East Asia, westermaniThiara containing China, Japan Oncomelania metacercariae Paragonimus spp.Cysts in lungs Sputum and faecesVariousEdible crustaceansSouth-East Asia,containingWest Africa, South andmetacercariaeCentral AmericaLiver Clonorchis sinensis Bile and pancreatic Faeces Bulimus Freshwater food sh South-East Asiaducts Parafossarulus containing metacercariae Opisthorchis felineus Bile and pancreatic Faeces Bithynia Freshwater food shSiberia, East Europeductscontaining metacercariae O. viverrini 5

Bile and pancreatic Faeces Bithynia Freshwater food shThailand, Laosductscontaining metacercariae Fasciola hepatica Bile ductsFaeces Lymnaea Metacercariae encysted Cosmopolitan (mainlyon plantstemperate areas)Intestine Fasciolopsis buski Small intestineFaeces Segmentina Metacercariae on South-East Asia, Indiawater plants Heterophyes Small intestineFaeces Pirenella Freshwater food sh South-East Asia, heterophyesCerithidea containing metacercariaeMiddle East, Egypt,southern Europe Metagonimus Small intestineFaeces Semisulcospira Freshwater food sh South-East Asia, Russia yokogawai containing metacercariae(Siberia), southern EuropeOther heterophyidsSmall intestineFaecesVariousFreshwater food sh Worldwide in warmcontaining metacercariaecountriesEchinostomesSmall intestineFaecesVariousFreshwater sh or snails Mostly South-Eastcontaining metacercariaeAsia, India Gastrodiscoides Caecum and colonFaeces Helicorbis Metacercariae on South-East Asia hominis water plants identication and study of the biology of the particular snails involved in transmis-sion form an important aspect of the epi-demiology of trematode diseases, known asmedical malacology.Detailed consideration of snail inter-mediate hosts is outside the scope of this book. For the practical eld worker it is nec-essary to consult a specialized monograph(e.g. Malek, 1963; Brown, 1980) or sendspecimens to an expert, as in most habitatsthere are species of snails present which donot transmit human helminth infections butclosely resemble those that do. Some of theimportant snail intermediate hosts involvedin the dissemination of trematodes of med-ical importance are shown in Fig. 1. Morphology The outer surface or tegument is a non-cellular syncytial extension of thesunken tegumental cells, and may havespines embedded in it. During the lastfew years a great deal of interest has been shown in the physiology and nestructure of the tegument of both trema-todes and cestodes, because of its impor-tance in nutrition and in antigenicstimulation (it is considered in moredetail on p.63 in the section oncestodes).Two suckers are present in all trema-todes found in humans, an anterior oralsucker into which the alimentary canal The Trematodes 5 Fig. 1. Snails that act as rst intermediate hosts of the trematodes of medical importance. 6

(a) Biomphalaria glabrata from Brazil, host of Schistosoma mansoni. (b) Bulinus ( Physopsis ) globosus from Nigeria and (c) Bulinus (Bulinus) truncatus from Iran, hosts of S. haematobium. (d) Oncomelania hupensis nosophora from Japan, host of S. japonicum. (e) Thiara granifera from China and (f) Semisulcospira libertina from China, hosts of Paragonimus westermani and Metagonimus yokogawai. (g) Polypylis hemisphaerula from China, host of Fasciolopsis buski. (h) Parafossarulus manchouricus from China, host of Clonorchis sinensis. (i) Codiella (= Bithynia ) leachi from Germany, host of Opisthorchis felineus. (j) Pirenella conica (from Egypt) host of Heterophyes heterophyes. (k) Lymnaea trunculatula from England, host of Fasciola hepatica

opens and a more posterior ventralsucker, or acetabulum, by which theworm attaches itself to its host. In Heterophyes 10

there is also an accessorygenital sucker.The features of importance in therecognition and classication of a trema-tode are shown in Fig. 2 and the morphol-ogy of the ukes of medical importancein Fig. 3. Life Cycle Stages Adults are hermaphrodite, except for theschistosomes, which have separate sexes the egg reaches water (in the schistosomes,opisthorchiids and heterophyids the eggcontains a larva, termed a miracidium,when passed out; in other trematodes thelarva develops inside the egg over a fewweeks) the ciliated miracidium larvahatches from the egg and penetrates a spe-cic freshwater snail (except inopisthorchiids, where the egg containing alarva is ingested by the snail) inside thesnail the miracidium develops into anirregular sac-like sporocyst germ cellsinside this primary sporocyst form the nextlarval stage (these are termed rediae inmost trematodes, where they have a rudi-mentary gut, but secondary sporocysts inschistosomes, where they are similar to theprimary sporocysts), which burst out andinvade new tissues of the snail (principallythe digestive gland) germ cells insidethese in turn develop into the next larvalstages, the tailed cercariae , which escapefrom the snail into the water (in someforms there are two redial generations).Thus one miracidium can give rise to manythousands of cercariae, the process takingseveral weeks or even months. The cer-cariae actively penetrate through the skin,as in the schistosomes, or form cysts( metacercariae ) in a second intermediatehost or on vegetation and are passivelyingested in all other trematodes. Classication The classication given below is based prin-cipally on that of La Rue (1957), in whichthe life history and the larval stages are con-sidered as well as the morphology of theadult; more conservative classications were based entirely on the adult. The divisions atthe family level are generally accepted bymost authorities, but those taxa above thislevel are still controversial (Gibson and Bray,1994). Recent studies utilizing computer- based cladistic analysis and molecular biol-ogy might alter the familiar groupings in the 6 Chapter 1 Fig. 2. Diagram of Clonorchis sinensis to showthe features of taxonomic importance in thedigenetic trematodes.

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future (Brooks et al. , 1985; Rohde et al. ,1993), but changes are not generallyaccepted. Only a very few of the numerousfamilies comprising the subclass Digenea areincluded (Yamaguti, 13

1971) those whichhave members of medical importance.The modes of infection of trematodesof medical importance shown in Table 2reect quite well the taxonomic divisions(the odd one out being Echinostoma , in which it might be expected that the cercariae would encyst on vegetation). The Trematodes 7 Fig. 3. Diagrams of the shape and principal organ systems of the hermaphrodite trematodes of medicalimportance (schistosomes are shown in Fig. 4). Comparative sizes shown in silhouette.

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