Abstract
Chemotherapy remains the only practicable tool to control falciparum malaria in sub-Saharan Africa, where >90% of the world's burden of malaria mortality and morbidity occurs. Resistance is rapidly eroding the efficacy of chloroquine, and the combination pyrimethamine-sulfadoxine is the most commonly chosen alternative. Resistant populations of Plasmodium falciparum were selected extremely rapidly in Southeast Asia and South America. If this happens in sub-Saharan Africa, it will be a public health disaster because no inexpensive alternative is currently available. This article reviews the molecular mechanisms of this resistance and discusses how to extend the therapeutic life of antifolate drugs.
MeSH terms
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Africa South of the Sahara
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Animals
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Antimalarials / pharmacology*
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Antimalarials / therapeutic use
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Chloroquine / pharmacology
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Drug Combinations
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Drug Resistance
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Humans
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Malaria, Falciparum / drug therapy*
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Microbial Sensitivity Tests
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Mutation
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Plasmodium falciparum / drug effects*
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Plasmodium falciparum / genetics
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Plasmodium falciparum / growth & development
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Pyrimethamine / pharmacology*
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Pyrimethamine / therapeutic use
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Sulfadoxine / pharmacology*
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Sulfadoxine / therapeutic use
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Tetrahydrofolate Dehydrogenase / metabolism
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Treatment Outcome
Substances
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Antimalarials
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Drug Combinations
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fanasil, pyrimethamine drug combination
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Sulfadoxine
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Chloroquine
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Tetrahydrofolate Dehydrogenase
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Pyrimethamine