Chemotherapy of Parasitic Diseases

I. Introduction.- 1 Historical Introduction.- 1. The Mission.- 2. General Evolution.- 3. Experimental Methods.- 3.1. Concept and Control.- 3.2. Some Specific Assay Applications.- 4. Antiprotozoal Agents.- 5. Anthelmintic Agents.- 5.1. Roundworms (Nematoda).- 5.2. Flukes (Trematoda).- 5.3. Tapeworms (Cestoda).- 6. Ectoparasites.- 7. The Past as Prologue.- References.- II. Protozoa.- 2 Chemistry of Antiprotozoal Agents.- 1. Introduction.- 2. Structural Categories.- 2.1. Organometallic Compounds.- 2.2. Substituted Carbocyclic Compounds.- 2.3. Heterocyclic Compounds.- 3. Properties of Antiprotozoal Agents.- References.- 3 Protozoan Infections of Man: Malaria.- 1. Introduction.- 2. Goals of Malaria Chemotherapy.- 2.1. Prophylaxis.- 2.2. Cure of Acute Malarial Attacks.- 2.3. Malaria Eradication Programs.- 3. Antimalarials and Their Uses.- 3.1. 8-Aminoquinolines: Primaquine.- 3.2. Quinine.- 3.3. Mefloquine.- 3.4. 4-Aminoquinolines: Chloroquine, Amodiaquine, Amopyroquine, and Hydroxychloroquine.- 3.5. Diaminopyrimidines: Pyrimethamine and Trimethoprim.- 3.6. Biguanides (Proguanil and Chlorproguanil) and Triazines (Cycloguanil).- 3.7. PABA Antagonists: Sulfonamides and Sulfones.- 3.8. Antibiotics: Tetracyclines (Tetracycline, Doxycycline, Minocycline) and Clindamycin.- 4. Guidelines for Malaria Chemotherapy.- 4.1. Treatment of P. vivax and P. ovale.- 4.2. Treatment of P. malariae.- 4.3. Treatment of P. falciparum.- 4.4. Treatment of Malaria in Children.- 4.5. Prophylaxis.- 5. Future Directions.- References.- 4 Protozoan Infections of Man: American Trypanosomiasis and Leishmaniasis.- 1. Introduction.- 2. American Trypanosomiasis (Chagas' Disease).- 2.1. Nifurtimox and Benznidazole.- 2.2. Clinical Strategy.- 2.3. The Future.- 3. Leishmaniasis.- 3.1. Pentavalent Antimonials.- 3.2. Second-Line Drugs.- 3.3. Clinical Strategy for Cutaneous and Mucosal Disease.- 3.4. Clinical Strategy for Visceral Disease.- References.- 5 Protozoan Infections of Man: African Trypanosomiasis.- 1. Introduction.- 2. Experimental Models.- 2.1. In Vitro.- 2.2. In Vivo.- 3. Currently Available Drugs.- 3.1. CNS- and Bloodstream-Active Drugs.- 3.2. Bloodstream-Active Drugs.- 4. Experimental Trypanocidal Drugs.- 4.1. Nitrofurans.- 4.2. Bloodstream-Active Drugs.- 4.3. Combination Therapy.- References.- 6 Protozoan Infections of Man: Other Infections.- 1. Introduction.- 2. Entamoeba histolytica.- 2.1. Clinical Considerations.- 2.2. Individual Agents.- 3. Naegleria and Acanthamoeba Species.- 3.1. Clinical Considerations.- 3.2. Specific Agents.- 4. Giardia lamblia.- 4.1. Clinical Considerations.- 4.2. Individual Agents.- 5. Trichomonas vaginalis.- 5.1. Clinical Considerations.- 5.2. Individual Agents.- 6. Dientamoeba fragilis.- 6.1. Clinical Considerations.- 6.2. Individual Agents.- 7. Balantidium coli.- 7.1. Clinical Considerations.- 7.2. Individual Agents.- 8. Cryptosporidium.- 8.1. Clinical Considerations.- 8.2. Individual Agents.- 9. Toxoplasma gondii.- 9.1. Clinical Considerations.- 9.2. Individual Agents.- 10. Isospora belli.- 10.1. Clinical Considerations.- 10.2. Individual Agents.- 11. Sarcocystis Species.- 11.1. Clinical Considerations.- 12. Pneumocystis carinii.- 12.1. Clinical Considerations.- 12.2. Individual Agents.- 13. Babesia Species.- 13.1. Clinical Considerations.- References.- 7 Protozoan Infections of Domestic Animals: Coccidian and Related Infections.- 1. Introduction.- 2. Evolution of Present-Day Chemotherapeutic Practices in Coccidiosis Control.- 3. Methods of Drug Testing.- 3.1. Laboratory Trials.- 3.2. Field Trials.- 4. Characteristics of Drugs and Their Limitations.- 4.1. Spectrum of Activity.- 4.2. Specific Activity.- 4.3. Clinical versus Static Mode of Action.- 4.4. Stage in the Life Cycle Most Sensitive to the Drug.- 5. Limitations in the Use of Anticoccidial Drugs.- 5.1. Toxicity.- 5.2. Drug-Resistance Potential.- 5.3. Drug Residues.- 5.4. Limitations in the Technology of Feed Manufacture or Other Means of Drug Delivery.- 5.5. Interference of Anticoccidial Drugs with Other Medicaments.- 5.6. Side Effects, Subclinical Toxicity, and Other Effects of Drugs.- 6. Drugs Used in the Prevention of Coccidiosis in Poultry.- 6.1. Drugs Used in Broiler Chickens.- 6.2. Drugs for Layer Pullets and Other Poultry.- 7. Treatment of Clinical Coccidiosis.- 7.1. Poultry.- 7.2. Mammalian Coccidiosis.- 8. Cryptosporidosis in Domestic Animals.- 8.1. Chemotherapy of Cryptosporidosis.- 9. Toxoplasma and Sarcocystis in Domestic Animals.- References.- 8 Hemoprotozoan Infections of Domestic Animals: Trypanosomiasis, Babesiosis, and Anaplasmosis.- 1. Introduction.- 2. Experimental Methods.- 3. Trypanosomiasis.- 3.1. Clinical Importance of Chemotherapy and Chemoprophylaxis.- 3.2. Trypanosoma brucei, T. evansi, and T. simiae.- 3.3. T. vivax and T. congolense.- 3.4. New Compounds of Potential Value.- 4. Babesiosis.- 4.1. Clinical Importance of Chemotherapy and Chemoprophylaxis.- 4.2. Treatment of Cattle Babesias.- 4.3. Treatment of Other Babesias of Domestic Animals.- 5. Theileriosis.- 5.1. Clinical Importance of Cattle Theilerias.- 5.2. Tetracyclines in the Chemoprophylaxis and Treatment of Cattle.- 5.3. New Agents in the Chemotherapy of Cattle.- 6. Anaplasmosis.- 6.1. Tetracyclines in the Treatment of Anaplasmosis.- 6.2. Other Compounds in the Treatment of Anaplasmosis.- 7. Conclusions.- References.- 9 Modes of Action of Antiprotozoal Agents.- 1. Introduction.- 2. Modes of Action of Antiprotozoal Agents.- 2.1. Malaria.- 2.2. Leishmania.- 2.3. Amoebae.- 2.4. Trypanosoma cruzi.- 2.5. African Trypanosomes.- 2.6. Eimeria.- 2.7. Other Protozoa.- 3. Conclusion.- References.- 10 Drug Resistance in Protozoa.- 1. Protozoal Infections of Humans.- 1.1. Toxoplasma gondii.- 1.2. Entamoeba histolytica.- 1.3. Giardia lamblia.- 1.4. Trichomonas vaginalis.- 1.5. Leishmania spp.- 1.6. Trypanosoma cruzi.- 1.7. Trypanosoma brucei rhodiense and T. b. gambiense.- 1.8. Plasmodium spp.- 2. Drug Resistance in Protozoal Infections of Animals.- 2.1. Trypanosoma spp.- 2.2. Coccidian Parasites.- References.- III. Nematodes.- 11 Chemistry of Antinematodal Agents.- 1. Introduction.- 2. Benzimidazoles.- 3. Imidazothiazoles.- 4. Tetrahydropyrimidines.- 5. Organophosphates.- 6. Avermectins and Milbemycins.- 7. Miscellaneous Antinematodal Compounds.- 7.1. Piperazines.- 7.2. Chlorinated Hydrocarbons.- 7.3. Phenols.- 7.4. Arsenicals.- 7.5. Ethanolamines.- 7.6. Cyanine Dyes.- 7.7. Isothiocyanates.- 7.8. Other Compounds.- 7.9. Miscellaneous Natural Products.- References.- 12 Nematode Infections of Man: Intestinal Infections.- 1. Introduction.- 2. General Principles and Methods.- 3. Major Infections and the Drugs of Choice.- 3.1. Ascariasis.- 3.2. Enterobiasis.- 3.3. Hookworm Infections.- 3.4. Strongyloidiasis.- 3.5. Trichuriasis.- 4. Less Common Intestinal Nematode Infections.- 4.1. Trichinosis.- 4.2. Trichostrongyliasis.- 4.3. Intestinal Capillariasis.- 4.4. Intestinal Angiostrongyliasis.- 4.5. Anisakiasis, Oesophagostomiasis, and Gnathostomiasis.- 5. Anthelmintics and Their Usage.- 5.1. Albendazole.- 5.2 Bephenium Hydroxynaphthoate.- 5.3. Cambendazole.- 5.4. Levamisole.- 5.5. Mebendazole and Flubendazole.- 5.6. Oxantel.- 5.7. Piperazine.- 5.8. Pyrantel Pamoate.- 5.9. Pyrvinium Pamoate.- 5. lO.Thiabendazole.- References.- 13 Nematode Infections of Man: Extraintestinal Infections.- 1. Introduction.- 2. Intralymphatic Filariae.- 2.1 Methods of Detecting Activity against Wuchereria and Brugia.- 2.2. Wuchereria bancrofti and Brugia spp. in Man.- 3. Onchocerca volvulus Infections.- 3.1. Screening Methods for Onchocercicidal Drugs.- 3.2. Chemotherapy in Man.- 4. Loa loa.- 5. Other Tissue-Dwelling Nematodes.- 5.1. Angiostrongylus cantonensis and A. malaysiensis.- 5.2. Toxocara canis.- 5.3. Hookworm Infections.- 5.4. Dracunculus medinensis Infection.- 5.5. Trichinella spiralis Infections.- References.- 14 Nematode Infections of Domestic Animals: Gastrointestinal Infections.- 1. Principles of Control.- 2. Routes of Administration.- 3. Testing of Anthelmintic Drugs.- 3.1. Critical Tests.- 3.2. Controlled Tests.- 3.3. Fecal Egg Counts.- 3.4. Tests for Arrested Larvae.- 3.5. Tests for Ovicidal Activity.- 4. Drugs in Current Use.- 4.1. Broad-Spectrum Drugs.- 4.2. Narrow-Spectrum Drugs.- References.- 15 Nematode Infections of Domestic Animals: Extraintestinal Infections.- 1. Introduction.- 2. General Principles and Methods.- 3. Treatment of Extraintestinal Nematodes.- 3.1. Filariae.- 3.2. Lungworms.- 3.3. Other Extraintestinal Nematodes of Domestic Animals.- References.- 16 Mode of Action of Antinematodal Drugs.- 1. Introduction.- 2. Important Physiological Requirements of Nematodes.- 2.1. Glucose Metabolism.- 2.2. Neuromuscular Coordination.- 2.3. Microtubular Integrity.- 3. Chemical Classes of Antinematodal Compounds and Their Effects.- 3.1. Phenothiazine.- 3.2. Benzimidazoles.- 3.3. Imidazoles and Other Cholinergic Agonists.- 3.4. Ivermectin.- 3.5. Organophosphates.- 3.6. Piperazine and Diethylcarbamazine.- 3.7. Salicylanilides and Substituted Phenols.- 3.8. Antimonials.- 3.9. Arsenicals.- 3.10. Naphtalene Sulfonic Acid.- 3.11. Isothiocyanate.- 3.12. Cyanine Dyes.- 4. New Areas for Antinematodal Drugs.- References.- 17 Drug Resistance in Nematodes.- 1. Introduction.- 2. Detection of Resistance.- 2.1. Indirect Methods.- 2.2. Direct Methods.- 3. Development of Anthelmintic Resistance in the Field.- 3.1. Australia.- 3.2. New Zealand.- 3.3. North America.- 3.4. Britain.- 3.5. Other Countries.- 4. Laboratory Study on Anthelmintic Resistance.- 4.1. Limitations of Laboratory Studies.- 5. Field Studies on Anthelmintic Resistance.- 6. Genetics of Resistance.- 7. Mechanisms of Resistance.- 8. Resistance in Relationship to Worm-Control Practices.- 9. New Developments of Nematode Control.- 9.1. Nonchemotherapeutic.- 9.2. Chemotherapeutic.- 10. Conclusion.- References.- IV. Trematodes.- 18 Chemistry of Antitrematodal Agents.- 1. Introduction.- 2. Chemistry of Antischistosomal Agents.- 2.1. Antimony Compounds.- 2.2. The Miracils.- 2.3. Bisanilino Compounds (or Aminophenols).- 2.4. Nitroheterocyclic Compounds.- 2.5. Praziquantel.- 2.6. Miscellaneous Substances.- 3. Chemistry of Fasciolicides.- 3.1. Halogenated Hydrocarbons.- 3.2. Halogenated Phenols and Bisphenols.- 3.3. Salicylanilides.- 3.4. Benzimidazoles.- 3.5. Bisanilino Compounds.- 3.6. Benzene Sulfonamides.- 4. Agents Effective against Dicrocoelium dentriticum.- References.- 19 Trematode Infections of Man.- 1. Introduction.- 2. Schistosomiasis.- 2.1. General Principles.- 2.2. Methods.- 2.3. Antischistosomal Drugs.- 3. Other Trematode Infections.- 3.1. General Principles and Methods.- 3.2. The Drugs.- References.- 20 Trematode Infections of Domestic Animals.- 1. Introduction.- 2. Methods.- 2.1. Primary Screening in the Laboratory.- 2.2. Secondary Screening.- 3. General Principles.- 3.1. Application Techniques for Trematode Control.- 3.2. Principles of Chemotherapy.- 3.3. Specificity in Chemotherapy of Trematodes.- 4. The Drugs and Their Uses.- 4.1. Fasciolidae.- 4.2. Dicrocoeliidae.- 4.3. Paramphistomata.- 4.4. Schistosomatidae.- 4.5. Intestinal Trematodes of Birds and Mammals.- References.- 21 Mode of Action of Antitrematodal Agents.- 1. Mode of Action of Trematocidal Agents.- 1.1. Modes of Action of Schistosomicidal Agents.- 1.2. Mode of Action of Fasciolicidal Agents and Agents Effective against Less Common Trematodes.- References.- V. Cestodes.- 22 Chemistry of Anticestodal Agents.- 1. Introduction.- 2. Anticestodal Agents.- References.- 23 Cestodal Infections of Man.- 1. Introduction.- 2. Experimental Methods.- 2.1. Techniques for Drug Testing against Adult Tapeworms in Vivo.- 2.2. Drug Testing against Adult Tapeworms in Vitro.- 2.3. Drug Testing against Larval Tapeworms in Vivo.- 2.4. Drug Testing against Larval Tapeworms in Vitro.- 2.5. Clinical Trials.- 3. Treatment of Infections Due to Taenia, Diphyllobothrium, Echinococcus, and Hymenolepis.- 3.1. Traditional Remedies.- 3.2. Old Drugs.- 3.3. New Drugs.- 4. Treatment of Taenia solium Infections.- 5. Treatment of Human Cysticercosis.- 5.1. Praziquantel.- 5.2. Metrifonate.- 5.3. Flubendazole.- 6. Treatment of Human Hydatidosis.- 6.1. Pharmacology.- 6.2. Dosage.- 7. Treatment of Less Common Cestode Infections.- 8. Conclusions.- References.- 24 Cestode Infections of Domestic Animals.- 1. Introduction.- 2. Tapeworms of Dogs and Cats.- 2.1. Introduction.- 2.2. Arecoline Hydrobromide.- 2.3. Bunamidine Hydrochloride.- 2.4. Niclosamide.- 2.5. Substituted Benzimidazoles.- 2.6. Nitroscanate.- 2.7. Praziquantel.- 3. Tapeworms of Sheep and Cattle.- 3.1. Introduction.- 3.2. Niclosamide.- 3.3. Bunamidine Hydroxynaphtoate.- 3.4. Benzimidazoles.- 3.5. Praziquantel.- 4. Tapeworms of the Horse.- 4.1. Introduction.- 4.2. Niclosamide.- 4.3. Pyrantel Pamoate.- 5. Tapeworms of Birds.- 5.1. Introduction.- 5.2. Niclosamide.- 5.3. Praziquantel.- References.- 25 Mode of Action of Anticestodal Agents.- 1. Introduction.- 2. Benzimidazoles.- 3. Bithionol.- 4. Bunamidine.- 5. Niclosamide.- 6. Nitroscanate.- 7. Paromomycin.- 8. Praziquantel.- 8.1. Vacuolization of the Tegument.- 8.2. Contraction of the Parasite Musculature.- References.- VI. Arthropods.- 26 Chemistry of Drugs Used against Arthropod Parasites.- 1. Introduction.- 2. General Considerations.- 3. Arthropod Antiparasiticals of Current Utility.- 3.1. Inorganics.- 3.2. Chlorinated Hydrocarbons.- 3.3. Organic Phosphates.- 3.4. Carbamates.- 3.5. Pyrethroid and Pyrethroidlike Pesticides.- 3.6. Miscellaneous.- 3.7. Repellents.- References.- 27 Insect Infestations of Man.- 1. Introduction.- 2. General Principles and Methods.- 3. Lice.- 3.1. Pediculus humanus capitis, the Head Louse.- 3.2. Pediculus humanus humanus, the Body Louse.- 3.3. Phthirus pubis, the Crab Louse.- 4. Parasitic Fly Larvae (Maggots).- 5. Fleas.- 5.1. Pulex irritans, the Common Flea.- 5.2. Tunga penetrans, the Chigoe or Jigger Flea.- 6. Linguatula and Armillifer: Tongue Worms.- References.- 28 Acarine Infestations of Man.- 1. Introduction.- 2. Scabies.- 2.1. Overview.- 2.2. Individual Agents.- 3. Demodicidosis.- 3.1. Overview.- 3.2. Individual Agents.- 4. Ticks and Chiggers.- References.- 29 Insect Infestations of Domestic Animals.- 1. Introduction and General Principles.- 1.1. Myiases.- 1.2. Lice.- 1.3. Fleas.- 2. Experimental Methods.- 2.1. Myiases.- 2.2. Lice.- 2.3. Fleas.- 3. The Drugs and Their Uses.- 3.1. Myiases.- 3.2. Lice.- 3.3. Fleas.- References.- 30 Acarine Infestation of Domestic Animals.- 1. Introduction.- 2. Testing of Acaricides.- 2.1. Laboratory Trials.- 2.2. Field Trials.- 3. Major Acarine Pests of Animals and Their Control.- 3.1. Cattle.- 3.2. Horses.- 3-3. Sheep and Goats.- 3.4. Swine.- 3.5. Poultry.- 3.6. Dogs and Cats.- References.- 31 Mode of Action of Agents Used against Arthropod Parasites.- 1. Introduction.- 2. Compounds Affecting the Nervous System.- 2.1. Pyrethroids.- 2.2. Avermectins.- 2.3. Formamidines.- 2.4. Organophosphates.- 2.5. Carbamates.- 2.6. Lindane (BHC/?-HCH) and Cyclodienes.- 3. Compounds Affecting Bioenergetic Pathways.- 3.1. Arsenic (Trioxide).- 3.2. Rotenone.- References.- 32 Drug Resistance in Arthropod Parasites.- 1. Introduction.- 2. Occurrence of Resistance.- 3. Toxicology.- 3.1. Spectrum of Effect between Drugs.- 4. Mechanisms.- 4.1. Penetration.- 4.2. Detoxication.- 4.3. Insensitivity.- 5. Countermeasures.- 5.1. Eradication of Resistant Strains.- 5.2. Control of Resistant Strains.- 6. Rational Choice of Alternative Drugs.- References.- Appendix: Generic and Proprietary Names of Antiparasitic Drugs.