Abstract
Combination antimalarial therapy may delay the spread of drug resistance, but clinical data supporting this notion are limited. For 1 year, we studied Ugandan children who were treated for uncomplicated malaria with sulfadoxine-pyrimethamine (SP), SP + amodiaquine (AQ), or SP + artesunate (AS). We compared treatment responses and the prevalence of resistance-conferring mutations of new infections with those of recrudescent infections due to parasites that survived prior treatment. Recrudescent infections were associated with the selection of SP resistance-conferring mutations in all treatment groups, but responses to repeat therapy differed. Compared with initial treatments, treatment of recrudescent infections was associated with a higher rate of treatment failure (hazard ratio [HR], 2.44; P=.01), for the SP group, but with a lower rate of treatment failure (HR, 0.40; P=.08), for the SP + AS group. Treatment failure in the SP + AQ group was uncommon, limiting the analysis of recrudescent parasites. Our results suggest that the use of combination antimalarial therapy in Africa may slow the spread of drug-resistant malaria and prolong the therapeutic life span of available treatment regimens.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amodiaquine / administration & dosage
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Amodiaquine / pharmacology
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Amodiaquine / therapeutic use*
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Animals
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Antimalarials / administration & dosage
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Antimalarials / pharmacology
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Antimalarials / therapeutic use*
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Artemisinins / administration & dosage
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Artemisinins / pharmacology
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Artemisinins / therapeutic use*
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Artesunate
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Child, Preschool
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Dihydropteroate Synthase / genetics
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Drug Administration Schedule
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Drug Combinations
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Drug Resistance* / genetics
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Drug Therapy, Combination
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Humans
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Infant
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Malaria, Falciparum / drug therapy*
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Malaria, Falciparum / parasitology
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Mutation
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Plasmodium falciparum / drug effects
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Pyrimethamine / administration & dosage
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Pyrimethamine / pharmacology
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Pyrimethamine / therapeutic use*
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Sesquiterpenes / administration & dosage
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Sesquiterpenes / pharmacology
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Sesquiterpenes / therapeutic use*
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Sulfadoxine / administration & dosage
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Sulfadoxine / pharmacology
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Sulfadoxine / therapeutic use*
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Tetrahydrofolate Dehydrogenase / genetics
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Treatment Failure
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Treatment Outcome
Substances
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Antimalarials
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Artemisinins
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Drug Combinations
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Sesquiterpenes
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Amodiaquine
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fanasil, pyrimethamine drug combination
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Artesunate
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Sulfadoxine
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Tetrahydrofolate Dehydrogenase
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Dihydropteroate Synthase
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Pyrimethamine