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Artemisinin versus nonartemisinin combination therapy for uncomplicated malaria: randomized clinical trials from four sites in Uganda

dc.creatorBanek, Kristin
dc.creatorYeka, Adoke
dc.creatorBakyaita, Nathan
dc.creatorStaedke, Sarah G.
dc.creatorTalisuna, Ambrose
dc.creatorKironde, Fred
dc.creatorKamya, Moses.R
dc.creatorNsobya, Samuel L.
dc.creatorKilian, Albert
dc.creatorSlater, Madeline
dc.creatorDorsey, Grant
dc.creatorWabwire-Mangen, Fred
dc.creatorRosenthal, Philip J.
dc.creatorReingold, Arthur
dc.date2012-02-16T09:31:59Z
dc.date2012-02-16T09:31:59Z
dc.date2005-07
dc.date.accessioned2018-09-04T12:32:28Z
dc.date.available2018-09-04T12:32:28Z
dc.identifierYeka, A., Banek, K., Bakyaita, N., Staedke, S.G., Kamya, M.R., Talisuna, A., Kironde, F., Nsobya, S.L., Kilian, A., Slater, M., Dorsey, G., Wabwire-Mangen, F., Rosenthal, P.J., Reingold, A. (2005). Artemisinin versus nonartemisinin combination therapy for uncomplicated malaria: randomized clinical trials from four sites in Uganda. PLoS Medicine, 2(7)
dc.identifier1549-1277
dc.identifier10.1371/journal.pmed.0020190
dc.identifierhttp://hdl.handle.net/10570/434
dc.identifier.urihttp://hdl.handle.net/10570/434
dc.descriptionBackground Drug resistance in Plasmodium falciparum poses a major threat to malaria control. Combination antimalarial therapy including artemisinins has been advocated recently to improve efficacy and limit the spread of resistance, but artemisinins are expensive and relatively untested in highly endemic areas. We compared artemisinin-based and other combination therapies in four districts in Uganda with varying transmission intensity. Methods and Findings We enrolled 2,160 patients aged 6 mo or greater with uncomplicated falciparum malaria. Patients were randomized to receive chloroquine (CQ) + sulfadoxine-pyrimethamine (SP); amodiaquine (AQ) + SP; or AQ + artesunate (AS). Primary endpoints were the 28-d risks of parasitological failure either unadjusted or adjusted by genotyping to distinguish recrudescence from new infections. A total of 2,081 patients completed follow-up, of which 1,749 (84%) were under the age of 5y. The risk of recrudescence after treatment with CQ+SP was high, ranging from 22% to 46% at the four sites. This risk was significantly lower (p < 0.01) after AQ+SP or AQ+AS (7%–18% and 4%–12%, respectively). Compared to AQ + SP, AQ + AS was associated with a lower risk of recrudescence but a higher risk of new infection. The overall risk of repeat therapy due to any recurrent infection (recrudescence or new infection) was similar at two sites and significantly higher for AQ + AS at the two highest transmission sites (risk differences = 15% and 16%, p < 0.003). Conclusion AQ+AS was the most efficacious regimen for preventing recrudescence, but this benefit was outweighed by an increased risk of new infection. Considering all recurrent infections, the efficacy of AQ+SP was at least as efficacious at all sites and superior to AQ+AS at the highest sites. The high endemicity of malaria in Africa may impact on the efficacy of artemisinin-based combination therapy.
dc.descriptionCenters for Disease Control/Association of Schools of Public Health cooperative agreement, ‘‘Malaria Surveillance and Control in Uganda’’ (SA3569 and S1932–21/21), and the Department for International Development (DFID).
dc.languageen
dc.publisherPublic Library of Science
dc.subjectMalaria control
dc.subjectDrug efficacy
dc.subjectDrug resistance
dc.subjectFalciparum malaria
dc.subjectParasitological failure
dc.subjectPlasmodium falciparum
dc.subjectArtemisinins Malaria
dc.subjectDrug resistance
dc.subjectAntimalarial treatment
dc.subjectArtemisinins
dc.subjectArtemisinin combination therapy
dc.titleArtemisinin versus nonartemisinin combination therapy for uncomplicated malaria: randomized clinical trials from four sites in Uganda
dc.typeJournal article, peer reviewed


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