Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 188, Issue 8, Pages 1231-1238Publisher
OXFORD UNIV PRESS INC
DOI: 10.1086/378523
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Funding
- FIC NIH HHS [TW01506, TW00007] Funding Source: Medline
- NIAID NIH HHS [AI43301] Funding Source: Medline
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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.
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