Chemotherapy of Gastrointestinal Helminths

Contributors J. H. Arundel • J. H. Boersema • C. F. A. Bruyning • J. H. Cross A. Davis • A. De Muynck • P. G. Janssens • W. S. Kammerer IF. Michel • M.H. Mirck • M.D. Rickard F. Rochette M. M. H. Sewell • H. Vanden Bossche

Editors H. Vanden Bossche • D.Thienpont • P.G. Janssens

UNIVERSITATS- BlfiUOTHElC

Springer-Verlag Berlin Heidelberg New York Tokyo Contents

CHAPTER 1 Introduction. A. DAVIS A. Pathogenic Mechanisms in Man 1 B. Modes of Transmission 2 C. Clinical Sequelae of Infection 3 D. Epidemiological Considerations 3 E. Chemotherapy 4 F. Conclusion 5 References 5

CHAPTER 2 Epidemiology of Gastrointestinal Helminths in Human Populations C. F. A. BRUYNING A. Introduction 7 B. Epidemiological or "Mathematical" Models and Control 8 C. Nematodes 11 I. Angiostrongylus costaricensis 11 II. Anisakis marina 12 III. Ascaris lumbricoides 14 IV. Capillaria philippinensis 21 V. Enterobius vermicularis 23 VI. Gnathostoma spinigerum 25 VII. Hookworms: Ancylostoma duodenale and Necator americanus . 26 VIII. Oesophagostoma spp 32 IX. Strongyloides stercoralis 33 X. Ternidens deminutus 34 XI. Trichinella spiralis 35 XII. Trichostrongylus spp 38 XIII. Trichuris trichiura 39 D. Trematodes 41 I. Echinostoma spp 41 II. Fasciolopsis buski 42 III. Gastrodiscoides hominis 44 IV. Heterophyes heterophyes 44 V. Metagonimus yokogawai 46 X Contents

E. Cestodes 47 I. Diphyllobothrium latum 47 II. Dipylidium caninum 50 III. Hymenolepis diminuta 51 IV. Hymenolepis nana 52 V. Taenia saginata 54 VI. Taenia solium 57 VII. Cysticercosis cellulosae 58 References 60

CHAPTER 3 Epidemiology and Control of Gastrointestinal Helminths in Domestic Animals J. F. MICHEL. With 20 Figures A. Introduction 67 I. Effect of Worm Infection on Production 68 II. Economic Effects 71 B. Spontaneous Regulation of Worm Burdens in the Host 72 I. Self-cure and Protection 73 II. Resistance to the Establishment of Worms 74 III. The Loss of Worms 76 IV. Arrested Development 79 V. Stunting and Morphological Effects 85 VI. Regulation of Egg Output 86 VII. Effect of Parturition and Lactation on Host Resistance .... 88 C. The Free-Living Stages 90 I. Development 92 II. Migration 93 III. Survival 94 IV. Herbage Infestations 95 D. Epidemiology of Gastrointestinal Nematode Infections ...... 98 I. Cattle 98 II. Sheep 101 III. Intraspecific Variation 104 E. The Control of Gastrointestinal Nematode Infections of Sheep and Cattle 107 I. Eradication 107 II. Suppressive Dosing 107 III. Monitoring and Forecasting 108 IV. Control Strategies 109 V. Dairy Followers Ill VI. Beef 113 VII. Sheep 114 VIII. Integration of Sheep and Cattle Grazing 115 F. Conclusions 117 References 118 Contents XI

CHAPTER 4

Pharmacology of Anthelmintics. H. VANDEN BOSSCHE. With 37 Figures A. Introduction 125 B. Albendazole 125 I. Pharmacokinetics 125 II. Toxicology 127 III. Mode of Action 127 C. Amoscanate 127 I. Pharmacokinetics 127 II. Toxicology 128 III. Mode of Action 128 D. Amidantel 128 Toxicology 129 E. Avermectins 129 Mode of Action 130 F. Bephenium Hydroxynaphthoate 131 I. Pharmacokinetics 132 II. Toxicology 132 III. Mode of Action 132 G. Bithionol 132 I. Toxicology 132 II. Mode of Action 133 H. Bitoscanate 133 I. Pharmacokinetics 133 II. Toxicology 133 I. Bromoxanide 133 J. Brotianide 134 K. Cambendazole 134 I. Pharmacokinetics 134 II. Toxicology 134 III. Mode of Action .134 L. Ciclobendazole 135 I. Pharmacokinetics 135 II. Toxicology 136 M. Closantel 136 I. Pharmacokinetics 136 II. Toxicology 136 III. Mode of Action 137 N. Dichlorophen 138 I. Toxicology 138 II. Mode of Action 138 O. Diphetarsone 138 P. Disophenol 139 I. Toxicology 139 II. Mode of Action 139 XII Contents

Q. Febantel 140 I. Pharmacokinetics 140 II. Toxicology 141 III. Mode of Action 141 R. Fenbendazole 141 I. Pharmacokinetics 141 II. Toxicology 143 III. Mode of Action 143 S. Flubendazole 143 I. Pharmacokinetics 144 II. Toxicology 144 III. Mode of Action 145 T. Levamisole and Tetramisole 145 I. Pharmacokinetics 146 II. Pharmacology 146 III. Toxicology 147 IV. Mode of Action 148 U. Mebendazole 148 I. Pharmacokinetics 149 II. Toxicology 150 III. Mode of Action 151 V. Metrifonate 152 I. Pharmacokinetics 152 II. Toxicology 153 III. Mode of Action 153 W. Morantel 153 I. Pharmacokinetics 154 II. Toxicology 154 III. Mode of Action 154 X. Niclosamide 154 I. Pharmacokinetics 154 II. Toxicology • ... 154 III. Mode of Action 155 Y. Oxantel 155 Z. Oxfendazole 156 I. Pharmacokinetics 156 II. Toxicology 157 III. Mode of Action 157 AA. Oxibendazole 157 I. Pharmacokinetics 158 II. Toxicology 158 III. Mode of Action 158 BB. Parbendazole 158 I. Pharmacokinetics 158 II. Toxicology 159 III. Mode of Action 159 CC. Paromomycin 159 Contents XIII

DD. Piperazine 160 I. Pharmacokinetics 160 II. Toxicology 161 III. Mode of Action 161 EE. Praziquantel 162 I. Pharmacokinetics 162 II. Toxicology 162 III. Mode of Action 163 FF. Pyrantel 164 I. Pharmacology 165 II. Toxicology 165 III. Mode of Action 165 GG. Pyrvinium Pamoate 166 HH. Rafoxanide 166 I. Toxicology 166 II. Mode of Action 166 II. Tetrachloroethylene 167 JJ. Tiabendazole 167 I. Pharmacokinetics 168 II. Toxicology 169 III. Mode of Action 169 KK. Thiophanate 170 I. Pharmacokinetics 171 II. Toxicology 171 References 171

CHAPTER 5 Chemotherapy of Gastrointestinal Nematodiasis in Man. P. G. JANSSENS A. Introduction 183 The Methodology of Drug Trials 188 B. Ancylostomiasis . 191 I. Introduction 191 II. Drugs 196 III. Drug Combinations 232 IV. General Comments 235 C. Anisakiasis 236 Introduction : 236 D. Ascariasis 240 I. Introduction 240 II. Drugs 250 III. Drug Combinations 276 E. Enterobiasis 277 I. Introduction 277 II. Drugs 281 III. Drug Combinations 293 IV. Comments 294 XIV Contents

F. Gnathostomiasis 294 I. Introduction 294 II. Drugs 296 G. Intestinal Angiostrongyliasis 296 I. Introduction 296 II. Drugs 298 III. Angiostrongyliasis 298 H. Intestinal Capillariasis 299 I. Introduction 299 II. Drugs 301 HI. General Comments 304 J. Oesophagostomiasis 304 I. Introduction 304 II. Drugs 306 K. Strongyloidiasis 307 I. Introduction 307 II. Drugs 314 III. Drug Combinations 327 L. Ternidens or False Hookworm Infection 328 I. Introduction 328 II. Drugs 329 III. Comments 329 M. Trichinosis 330 I. Introduction 330 II. Drugs 333 III. Comments 337 N. Trichostrongyliasis 337 I. Introduction 337 II. Drugs 339 O. Trichuriasis 342 I. Introduction 342 II. Drugs 347 III. Drug Combinations 367 References 368

CHAPTER 6 Chemotherapy of Gastrointestinal Nematodiasis in Ruminants J. H. BOERSEMA A. Introduction 407 B. Factors and Circumstances Influencing the Choice of Anthelmintic . 407 I. Diagnosis 407 II. Toxicity at the Therapeutic Dose and Drug Interactions . . . 408 III. Formulation 409 IV. Presence of Inhibited Larvae 411 V. Ovicidal Effect 412 VI. Resistance 412 Contents XV

C. The Anthelmintics 413 I. Phenothiazine 413 II. Bephenium 413 III. Organic Phosphorus Compounds 418 IV. Metyridine 420 V. Nitrophenols 420 VI. Benzimidazoles 421 VII. Salicyclanilides 427 VIII. Tetrahydropyrimidines 428 IX. Imidazothiazoles 429 X. Probenzimidazoles 431 XI. Avermectins 432 References 433

CHAPTER 7 Chemotherapy of Gastrointestinal Nematodiasis in Equines. M. H. MIRCK A. Introduction 443 B. Strongylidae 443 I. Epidemiology 444 II. Prevention and Treatment 444 III. Drug Resistance 447 C. Other Important Nematodes 448 D. Anthelmintics 449 I. Phenothiazine 449 II. Piperazine 449 III. Organophosphates 449 IV. Tetrahydropyrimidines 450 V. Imidazothiazoles 451 VI. Benzimidazoles 452 VII. Benzimidazole Carbamates 452 VIII. Febantel . 455 IX. Avermectins 455 E. Conclusions 456 References 456

CHAPTER 8 Chemotherapy of Gastrointestinal Nematodiasis in Pigs. F. ROCHETTE A. Introduction 463 B. Pig Nematodes 464 I. Ascaris suum 464 II. Strongyloides ransomi 465 III. Hyostrongylus rubidus 466 IV. Oesophagostomum dentatum, O. quadrispinulatum 466 XVI Contents

V. Trichuris suis 467 VI. Spiruroidea 467 VII. Trichinella spiralis 467 C. Pen Hygiene and Pasture Management 468 D. Herd Deworming 469 E. Anthelmintics 471 I. Piperazines 471 II. Organophosphates 471 III. Tetrahydropyrimidines 474 IV. Imidazothiazoles 474 V. Benzimidazoles 475 VI. Benzimidazole Carbamates 476 VII. Probenzimidazoles 478 VIII. Avermectins 479 References 479

CHAPTER 9 Chemotherapy of Gastrointestinal Nematodiasis in Carnivores F. ROCHETTE A. Introduction 487 B. Gastrointestinal Nematodes of Dogs and Cats 487 I. Ascarids 488 II. Hookworms 489 III. Whipworms 489 C. Prevention and Treatment 490 D. Older and Superseded Anthelmintics 491 I. Piperazine 491 II. Diethylcarbamazine 492 III. Methylbenzene 492 IV. Dithiazanine 492 V. Disophenol \ 492 VI. Thenium 493 VII. Metyridine 493 VIII. Nitrodan 493 E. Organophosphates 493 Dichlorvos 493 F. Tetrahydropyrimidines 494 Pyrantel, Morantel 494 G. Imidazothiazoles 495 Tetramisole, Levamisole 495 H. Nitroscanate 496 J. Benzimidazoles 496 I. Tiabendazole 496 II. Mebendazole 496 III. Fenbendazole 499 IV. Albendazole 499 Contents XVII

K. Avermectins 500 L. Ticarbodine 500 M. Tioxidazole 500 N. Conclusions 500 References 500

CHAPTER 10 Chemotherapy of Gastrointestinal Nematodiasis in Birds. J. H. BOERSEMA A. Introduction 505 B. Nematodes in Domestic Birds 505 I. Ascaridia 505 II. Heterakis 505 III. Capillaria 506 IV. Amidostonum 506 C. General Remarks 506 D. The Anthelmintics 506 I. Phenothiazine 510 II. Piperazine 510 III. Metyridine 510 IV. Organic Phosphorus Compounds 511 V. Nitrophenols 512 VI. Benzimidazoles 512 VII. Tetrahydropyrimidines 515 VIII. Imidazothiazoles 515 IX. Probenzimidazoles 516 X. Avermectins 517 References 517

CHAPTER 11 Chemotherapy of Intestinal Trematodiasis in Mammals and Birds M. M. H. SEWELL A. Introduction 521 B. Intestinal Trematodes of Mammals 521 I. Ruminants 521 II. Equines 524 III. Pigs 525 IV. Dogs 526 V. Other Carnivores 529 VI. Elephants 529 C. Intestinal Trematodes of Birds 529 D. Chemotherapeutic Agents 530 I. Halogenated Hydrocarbons 530 II. Salicylanilides and Substitutet Phenols 532 III. Other Chemotherapeutic Agents 535 References 536 XVIII Contents CHAPTER 12 Chemotherapy of Intestinal Trematodiasis in Man. J. H. CROSS A. Introduction 541 B. Fasciolopsiasis 541 I. Introduction 541 II. Morphology 542 III. Life Cycle 542 IV. Pathology 542 V. Diagnosis 543 VI. Treatment 543 VII. Socioeconomic, Ecological, and Cultural Aspects 544 C. Heterophyidiasis 545 I. Introduction 545 II. Morphology 545 III. Life Cycle 546 IV. Pathology 546 V. Diagnosis 547 VI. Treatment 547 VII. Socioeconomic, Ecological, and Cultural Aspects 547 D. Echinostomatidiasis 548 I. Introduction 548 II. Morphology 549 III. Life Cycle 549 IV. Pathology 549 V. Diagnosis 549 VI. Treatment 549 VII. Socioeconomic, Ecological, and Cultural Aspects 550 E. Gastrodisciasis 551 I. Introduction 551 II. Morphology 551 III. Life Cycle 551 IV. Pathology 551 V. Diagnosis 551 VI. Treatment 551 VII. Socioeconomic, Ecological, and Cultural Aspects 552 F. Lecithodendriidiasis 552 I. Introduction 552 II. Morphology 552 III. Life Cycle 552 IV. Pathology 553 V. Diagnosis 553 VI. Treatment 553 VII. Socioeconomic, Ecological, and Cultural Aspects 553 G. Other Human Intestinal Trematodiasis 554 H. Comment 554 References 555 Contents XIX

CHAPTER 13 Chemotherapy of Tapeworm Infections in Animals M. D. RICKARD and J. H. ARUNDEL. With 5 Figures A. Introduction 557 B. Cestodes of Veterinary Importance 558 I. Order Pseudophyllidea 560 II. Order Cyclophyllidea 562 C. Chemotherapeutic Agents 577 I. Arecoline 577 II. Dichlorophen 581 III. Di-w-Butyl Tin Dilaurate 581 IV. Niclosamide 582 V. Bunamidine 584 VI. Nitroscanate 587 VII. Praziquantel 588 VIII. Benzimidazoles 590 IX. Antibiotics 595 X. Diuredosan 596 XI. Fospirate 597 XII. Other Compounds 597 D. Recommended Treatments for Cestode Infections 599 References 599

CHAPTER 14 Chemotherapy of Tapeworm Infections in Man. W. S. KAMMERER A. Introduction 613 B. General Features of Human Cestode Infections 613 C. Niclosamide 614 Results in Clinical Trials - Adult Cestode Infections 614 D. Mebendazole . 616 Results in Clinical Trials 617 E. Praziquantel 620 Results in Clinical Trials 621 F. Summary 623 References 625

CHAPTER 15 Mass Treatment. P. G. JANSSENS and A. DE MUYNCK A. Introduction 631 I. Standpoints and Prejudices 632 II. Pathogenicity 633 B. Epidemiology 633 XX Contents C. A Mass Treatment Campaign 635 I. Definition 635 II. Organization 636 III. Preliminary Survey 639 IV. Preplanning Stage 640 V. Planning Stage 645 VI. Execution Stage 645 D. Alternative Control Measures 646 E. Conclusion 647 Appendix A: Questionnaire 647 Appendix B: Stool Examination 650 Appendix C: Clinical Examination 651 Appendix D: Instructions for the File 651 References 653

List of International Nonproprietary United States Adopted and Trade Names of Some Anthelmintics 655

Subject Index 659