Roles of parasites in disease
Roles of parasites in disease Blood and bone marrow • Blood: • Malaria (Plasmodium) • Babesiosis • Filariasis • Bone marrow: • Leishmaniasis Central nervous system • Meningoencephalitis: • Brain abscess: • • • • • Naegleria fowleri Toxoplasma Taenia solium Schistosoma japanicum Acanthamoeba Other involvements • Eye • Chirrhosis • Cystitis • Vaginitis/Uretritis: Tricomonas vaginalisHeart • Lung • Lymphatics • Intestinal tract • Muscle Antiparasitic drugs difficulties of effective chemotherapeutic intervention for parasites • eukaryotic • thus are more similar to the human host • chronic and prolonged course of infection • the complex life cycles • multiple developmental stages of many parasites Antiparasitic drugs • Unfortunately, few of the antiinfective agents that have proved so successful against bacterial pathogens have been effective against parasites. • In many instances, clinicians continue to rely on antiparasitic agents from the preantibiotic era. • These and some newer agents remain limited in effectiveness and are relatively toxic. Many antiparasitic agents require prolonged or parenteral administration and may be effective only in certain disease states. • Fortunately, in the last 5 to 10 years, several new agents have appeared that constitute significant advances in the treatment of parasitic diseases. In each case, the previously available drugs were toxic and often ineffective. Additional complicating factors in developing countries, where the majority of parasitic diseases occur (1) the presence of multiple infections and the high probability of reinfection (2) the large number of persons immunocompromised by malnutrition and human immunodeficiency virus infection (3) the overwhelming influence of poverty and poor sanitation, which facilitate the transmission of many parasitic infections. chemotherapeutic approaches • some agents have adverse effects or eventually meet with resistance • too expensive for widespread use in developing countries. • Thus the global approach to the prevention and treatment of parasitic diseases must involve several strategies, including improved hygiene and sanitation, control of the disease vector, use of vaccinations if available (largely unavailable for parasitic diseases), and prophylactic and therapeutic administration of safe and effective chemotherapy. • Of note, large-scale chemotherapy administered one to three times per year in endemic regions has reduced transmission of, and morbidity and mortality from, certain infections, including lymphatic filariasis, onchocerciasis, schistosomiasis, and intestinal nematodes. • These strategies now must also include efforts to decrease the transmission of infection by the human immunodeficiency virus. Antiprotozoal Agents • Heavy Metals • Melarsoprol :trypanosomiasis • Quinoline Derivatives • Chloroquine: Chloroquine remains the drug of choice for the prophylaxis and treatment of susceptible malaria strains • quinine, quinidine • primaquine and the synthetic quinoline compounds (mefloquine, halofantrine, lumefantrine). Antiprotozoal Agents • Folic acid antagonists • Pyrimethamine • Trimethoprim • Sulfonamides • Trimethoprim+sulfametaxazole: Toxoplasma Antiprotozoal Agents • Inhibitors of Protein Synthesis • Clindamycin and the tetracyclines are active against Plasmodium species, Babesia species, and amebae. • Doxycycline is used for the chemoprophylaxis of chloroquine-resistant P. falciparum malaria, and tetracycline may be used with quinine for the treatment of chloroquineresistant P. falciparum infection. • Clindamycin may be useful in the treatment of central nervous system toxoplasmosis. • Spiramycin is recommended as an alternative to the antifolates in the treatment of toxoplasmosis. Antiprotozoal Agents • Diamidines • Pentamidine, a diamidine, is a relatively toxic agent. Pentamidine is a polycation and may interact with DNA, or it may interfere with the uptake and function of polyamines. • Pentamidine is effective in treating the tissue forms of leishmania and the early (pre– central nervous system) forms of African trypanosomiasis. Antiprotozoal Agents • Nitroimidazoles • Metronidazole , tinidazole : • Trichomoniasis • Giardiasis • Amebiasis Antiprotozoal Agents • • • • Sesquiterpenes Atovaquone-Proguanil (Malarone) Miltefosine Nitazoxanide: broad-spectrum activity against numerous intestinal protozoa and helminths. Anthelmintic drugs • The strategy for the use of anthelmintic drugs is quite different from that for the use of drugs for treating most protozoal infections. Most anthelmintic drugs are targeted at nonproliferating adult organisms, whereas with protozoa the targets are generally younger, more rapidly proliferating cells. Anthelmintic drugs • Benzimidazoles • mebendazole, thiabendazole triclabendazole, and albendazole • The benzimidazoles have a wide spectrum of activity, including intestinal nematodes (Ascaris, Trichuris, Necator, and Ancylostoma species; Enterobius vermicularis), as well as a number of cestodes (Taenia, Hymenolepis, and Echinococcus species) Anthelmintic drugs • Tetrahydropyrimidines • Pyrantel pamoate: Ascaris species, hookworm, and Trichuris species. • Piperazines • diethylcarbamazine (DEC):filariasis Anthelmintic drugs • Avermectins • Pyrazinoisoquinolines • Phenols:Niclosamide
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