Plasmodium vivax drug resistance

Four species of plasmodium typically cause human malaria Plasmodium falciparum, P vivax, P malariae, and P ovale. A fifth species, P knowlesi, is primarily a pathogen of monkeys, but has recently been recognized to cause illness, including severe disease, in humans in Asia. Although all of the latter species may cause significant illness, P falciparum is responsible for the majority of serious complications and deaths. Drug resistance is an important therapeutic problem, most notably with P... 

Mefloquine, a fluorinated derivative of 4-quinoline methanol, is a product of the US Army s antimalarial research program. It is active against chloroquine-resistant Plasmodium falciparum, and has an excellent schizonti-cidal effect in the blood in experimentally induced Plasmodium vivax infections in volunteers. It is not gametocidal. P. vivax infections can persist after successful treatment of the falciparum infection with other drugs the fact that mefloquine is effective against both organisms is thus of practical importance (SEDA-13, 808). 

As a result, the drug combination (Fansidar) appears to have improved drug-mediated disruption of folic acid in Plasmodium sp. (35,43). This combination has been used with quinine for the treatment and prevention of chloroquine-resistant malaria Plasmodium falciparum, Plasmodium ovale, Plasmodium vivax, and Plasmodium malaria). The combination therapy (Fansidar) has the added advantage of being inexpensive, which is essential for successful therapy in developing countries. When used on its own, pyrimethamine is a blood schizonticide without effects on the tissue stage of the disease. 

After war broke out in the Pacific at the end of 1941, the Dutch quinine plantations in the East Indies became inaccessible, and synthetic alternatives like chloroquine (see p433) came into use. These drugs were successful for some years, but after a while the Plasmodium falciparum and Plasmodium vivax parasites developed resistance to chloroquine and other antimalarial drugs, meaning that new treatments were needed. 

The half-life of mefloquine in the human body averages 15 days. Unlike quinine, it has a very high therapeutic index. Intensive clinical studies have shown it to be safe and effective in curing both falciparum and vivax types of malaria, regardless of whether these are resistant to chloroquine. Fears that resistance to mefloquine would be initiated by indiscriminate use of this drug are limiting its curative use to areas where chloroquine-resistant strains of Plasmodium flourish. Yor prophylactic use in such areas, it is combined with the pyrimethamine-sulfadoxine pair to decrease likelihood of resistance developing, in accord with principles discussed in Section 6.5. For clinical details, see Schmidt et al. (1978) for the overall picture on mefloquine, see WHO (1983). 

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