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[Present status and new approach to anti-parasite therapy]
Abstract:
New highly effective molecules have been developed for the treatment of human parasites due to the development resistances and newly described types of parasitosis. In man as in animals, chemoresistant strains of parasites are rare, even for Plasmodium species where decreased sensibility has been observed basically due to monotherapies given for too short periods. Many resistance mechanisms have been elucidated. Most antiparasite drugs are metabolized in the liver and alterations in the mitochondrial oxidative system, particularly in hepatic fasciolasis and amibiasis, may limit the production of active derivatives. Modifications in the host-parasite relations may also have an effect as has been observed in patients with acquired immunodeficiency syndrome. Several approaches suggest new therapeutic perspectives. Since most protozoa require large amounts of energy to maintain motility and asexual reproduction, blocking aerobic glycolysis has been suggested but is limited by toxic effects. Blocking protein metabolism is another possibility since intracellular protozoa cannot synthesize purines. Parasites also rely on the host for cholesterol, phospholipids and other lipids and blocking their uptake into the parasite is another possibility. Promising results have been obtained in vitro against Plasmodium berghei and P. chabaudi. Other approaches include inhibiting drug outflow from the parasite incapable of metabolizing it. Nonesense oligonuclides could be coupled with active drugs and induce irreparable damage to the parasite. In addition to these new therapeutic possibilities, better use of traditional drugs should be emphasized.(ABSTRACT TRUNCATED AT 250 WORDS)