Abstract

Diseases caused by protozoa affect more people than those brought on by any other biological cause. There are over 60,000 species of protozoa, of which some 10,000 are parasitic. In humans, protozoa chiefly infect the gastrointestinal tract, vagina, urethra, blood, and blood-forming organs. Malaria is the most widespread of the protozoan diseases, and is responsible for the greatest number of deaths due to infection. Protozoan diseases impact severely on people of tropical areas where there is widespread malnutrition, minimal health education, and poor sanitation. Fatal protozoal infections are occurring to an increased extent in the more developed countries among immunosuppressed individuals, especially those with AIDS. Amebiasis, a widespread disease of humans, is believed to be the third leading cause of death due to parasites. The disease is caused by pathogenic strains of the protozoan Entamoeba histolytica. Amebiasis antiprotozoal agents include metronidazole (C₆H₉N₃O₃), iodoquinol (C₉H₅I₂NO), oxytetracycline (C₂₂H₂₄N₂O₉), and others. Anaplasmosis is a tick-borne disease of cattle and other ruminants, such as deer in the western United States and elk in the former USSR, caused by the protozoan Anaplasma marginale. Horseflies are also vectors of the disease. Anaplasmosis antiprotozoal agents include imidocarb (C₁₉H₂₀N₆O) and chlortetracycline (C₂₂H₂₃ClN₂O₈). Babesiasis (babesiosis, piroplasmosis), primarily a disease of cattle, is caused by a protozoan Babesia microti. Babesiasis antiprotozoal agents include quinine (sulfate) plus clindamycin, and chloroquine pentamidine (C₁₉H₂₄N₄O₂). Balantidiasis (balantidiosis, balantidial dysentery) is an intestinal disease caused by the large ciliated protozoan, Balantidium coli. The infection can be cured most readily with tetracycline, oxytetracycline, or chlorotetracycline. Coccidiosis is a widespread disease that occurs most often in fowl, such as chickens and turkeys, and other farm animals (cows, sheep, swine, horses, and rabbits). It is caused by a combination of infective Emeria protozoa. Anticoccidial drugs are primarily prophylactic, rather than curative. The most common are salinomycin (C₄₂H₇₀O₁₁) and the sodium salt of monensin (C₃₆H₆₂O₁₁). Giardiasis, a waterborne enteric disease caused by Giardia lamblia, is the most prevalent protozoal disease found in humans in the United States; the Rocky Mountain region is a particularly highly endemic area. Treatment of giardiasis is most successful with quinacrine (C₂₃H₃₀ClN₃O) or its hydrochloride. Hexamitosis is a disease of chickens, turkeys, quail, and pheasants in which there is an infectious catarrhal enteritis in the duodenum and small intestine caused by the protozoan Hexamita meleagridis. There is no effective treatment for hexamitosis. Histomoniasis (histomonas, enterohepatitis, blackhead disease), caused by Histomonas meleagridis, is primarily an affliction of chickens and turkeys. A favored treatment for histomoniasis is dimetridazole (C₅H₇N₃O₂). Leishmaniasis, which affects some 12 million humans annually, is a complex of at least two protozoan (species of Leishmania) diseases, consisting primarily of cutaneous and visceral forms. Leishmaniasis can often be fatal, especially in the visceral form. Pentavalent antimony preparations, the most important of which are sodium stibogluconate () and glucantime (N-methylglucamine antimonate, C₇H₁₈NO₈Sb, meglumine antimonate). Malaria affects an estimated 270 million people and causes 2–3 million deaths annually. The responsible protozoa are from the genus Plasmodium. The species that infect humans are P. falcipanium, P. vivax, P. malariae, and P. ovale. The vector is the female Anopheles mosquito. Antimalarials can be categorized according to their mode of action, ie, tissue schizonticides, blood schizonticides, gametocytocides, sporontocides. Antimalarials include 4-quinolinemethanols [quinine, quinidine (sulfate) (), and mefloquine (C₁₇H₁₆F₆N₂O)], phenanthrene-methanols [halofantrine (C₂₆H₃₀Cl₂F₃NO)], 4-aminoquinolines [chloroquine, amodiaquine, and hydroxychloroquine (C₁₈H₂₆ClN₃O)], 8-aminoquinolines [pamaquine (C₁₉H₂₉N₃O) and primaquine (phosphate) ()], antifolates [dapsome (C₁₂H₁₂N₂O₂S), sulfadoxine (C₁₂H₁₄N₄O₄S), sulfadiazine, sulfalene (C₁₁H₁₂N₄O₃S), pyrimethamine, trimethoprim (C₁₄H₁₈N₄O₃), chlorguanide (C₁₁H₁₆ClN₅), and cycloguanil (C₁₁H₁₄ClN₅)]. Other antimalarial drugs include menoctone (C₂₄H₃₂O₃), pyronaridine (C₂₉H₃₂ClN₅O₂, tetracycline, doxycycline (C₂₂H₂₄N₂O₈), minocycline chloramphenicol (C₁₁H₁₂Cl₂N₂O₅), clindamycin, febrifugine (C₁₆H₁₉N₃O₃), artemisinin (C₁₅H₂₂O₅), artemether (C₁₆H₂₆O₅), arteether (C₁₇H₂₈O₅), the sodium salt of artesunic acid (C₁₉H₂₈O₈), and the sodium salt of artelinic acid (C₂₃H₃₀O₇). Although the organism responsible for pneumocystosis in humans, Pneumocystis carinii, is harbored by a wide variety of animals and most people without any apparent adverse effect, acute pneumocystosis rarely strikes healthy individuals. P. carinii becomes active only in those individuals who have a serious impairment of their immunologic systems (eg, AIDS patients). The drug of choice is the antifolate mixture, trimethoprim and sulfamethoxazole (C₁₀H₁₁N₃O₃S). Theileriasis (theileriosis), a tick-transmitted protozoan disease of cattle seen primarily in central and eastern Africa, is caused by the protozoan Theileria parva (Piroplasma kochi, Piroplasma parvum, Theileria kochi, Theileria lawrencei). There are no fully effective therapeutic agents for the treatment of theileriasis. Toxoplasmosis, a coccidial disease, affects both humans and animals throughout the world. Approximately one-third of the population has antibodies to it but is asymptomatic. Toxoplasmosis is an increasingly important opportunistic disease that afflicts immunocompromised hosts such as post-transplant patients taking immunosuppressive drugs and AIDS patients. Toxoplasmosis is caused by the protozoan Toxoplasma gondii. In humans the disease is generally acquired by eating inadequately cooked meat or by association with infected felines. The cyst of T. gondii is persistant, making long-term therapy a requirement in patients whose immune systems are compromised. Treatment of cerebral or ocular toxoplasmosis is generally accomplished with antifolate compounds consisting of a combination of pyrimethamine and a long-acting sulfonamide such as sulfadiazine. There is evidence that the related mixture of trimethoprim plus sulfamethoxazole is nearly as effective but less toxic than the pyrimethamine combinations. Trichomoniasis is a widespread disease of the urogenital tract caused by the protozoan Trichomonas vaginalis. This sexually transmitted disease affects humans only and has no known animal reservoirs. Treatment by the 5-nitroimidazole class of antiprotozoal agents can destroy most strains of T. vaginalis; however, some strains have been reported to be resistant to these drugs. The agent of choice is orally administered metronidazole. The disease trypanosomiasis has two geographically delineated forms, the so-called African and American varieties. According to the World Health Organization, African trypansomiasis, caused by Trypanosoma brucci, affects some 25,000 people annually in 36 sub-Saharan countries where 50 million inhabitants are at risk. It is the cause of sleeping sickness, a disease transmitted by the bite of either the female or male tsetse fly. The early stages of African trypanosomiasis, ie, before central nervous system involvement and the sleeping sickness take effect, can be best treated with intravenous suramin sodium (C₅₁H₃₄N₆Na₆O₂₃S₆). For late-stage disease, in which the central nervous system is implicated, the compound of choice until recently was melarsoprol (C₁₂H₁₅AsN₆OS₂) for the T. b. gambiense or T. b. rhodesiense. The first new treatment in 40 years that is showing great promise is eflornithine. American trypanosomiasis, known as Chagas' Disease, is limited to South and Central America, where it affects 16–18 million people annually in an area where 90 million are at risk. The protozoan causative agent, Trypanosoma cruzi, is harbored in domesticated animals, such as dogs, cats, and pigs, as well as wild animals, eg, rats, bats, foxes, opossums, and monkeys. The nitrofuran nifurtimox is the most effective drug against T. cruzi. Benznidazole (C₁₂H₁₂N₄O₃) is an alternative drug, although relapses are common. Primaquine is effective against extracellular trypanosomes in the blood.