Dorsey, Grant; Vlahos, Jonathan; Kamya, Moses R; Staedke, Sarah G; Rosenthal, Philip J; (2003) Prevention of increasing rates of treatment failure by combining sulfadoxine-pyrimethamine with artesunate or amodiaquine for the sequential treatment of malaria. The Journal of infectious diseases, 188 (8). pp. 1231-1238. ISSN 0022-1899 DOI: https://doi.org/10.1086/378523
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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.