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A head-to-head comparison of four artemisinin-based combinations for treating uncomplicated malaria in African children: a randomized trial

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dc.contributor.other D'Alessandro, U.
dc.contributor.other Menten, J.
dc.contributor.other Van Loen, H.
dc.contributor.other Ravinetto, R. 2012-03-30T12:45:10Z 2012-03-30T12:45:10Z 2011
dc.identifier.issn 1549-1277
dc.identifier.other ITG-P5A
dc.identifier.other ITG-I20A
dc.identifier.other ITG-I33A
dc.identifier.other ITG-I43B
dc.identifier.other PARAS
dc.identifier.other U-MALAR
dc.identifier.other INTER
dc.identifier.other U-CTU
dc.identifier.other JIF
dc.identifier.other DOI
dc.identifier.other FTA
dc.identifier.other Abstract
dc.identifier.other UPD44
dc.description.abstract BACKGROUND: Artemisinin-based combination therapies (ACTs) are the mainstay for the management of uncomplicated malaria cases. However, up-to-date data able to assist sub-Saharan African countries formulating appropriate antimalarial drug policies are scarce. METHODS AND FINDINGS: Between 9 July 2007 and 19 June 2009, a randomized, non-inferiority (10% difference threshold in efficacy at day 28) clinical trial was carried out at 12 sites in seven sub-Saharan African countries. Each site compared three of four ACTs, namely amodiaquine-artesunate (ASAQ), dihydroartemisinin-piperaquine (DHAPQ), artemether-lumefantrine (AL), or chlorproguanil-dapsone-artesunate (CD+A). Overall, 4,116 children 6-59 mo old with uncomplicated Plasmodium falciparum malaria were treated (1,226 with AL, 1,002 with ASAQ, 413 with CD+A, and 1,475 with DHAPQ), actively followed up until day 28, and then passively followed up for the next 6 mo. At day 28, for the PCR-adjusted efficacy, non-inferiority was established for three pair-wise comparisons: DHAPQ (97.3%) versus AL (95.5%) (odds ratio [OR]: 0.59, 95% CI: 0.37-0.94); DHAPQ (97.6%) versus ASAQ (96.8%) (OR: 0.74, 95% CI: 0.41-1.34), and ASAQ (97.1%) versus AL (94.4%) (OR: 0.50, 95% CI: 0.28-0.92). For the PCR-unadjusted efficacy, AL was significantly less efficacious than DHAPQ (72.7% versus 89.5%) (OR: 0.27, 95% CI: 0.21-0.34) and ASAQ (66.2% versus 80.4%) (OR: 0.40, 95% CI: 0.30-0.53), while DHAPQ (92.2%) had higher efficacy than ASAQ (80.8%) but non-inferiority could not be excluded (OR: 0.35, 95% CI: 0.26-0.48). CD+A was significantly less efficacious than the other three treatments. Day 63 results were similar to those observed at day 28. CONCLUSIONS: This large head-to-head comparison of most currently available ACTs in sub-Saharan Africa showed that AL, ASAQ, and DHAPQ had excellent efficacy, up to day 63 post-treatment. The risk of recurrent infections was significantly lower for DHAPQ, followed by ASAQ and then AL, supporting the recent recommendation of considering DHAPQ as a valid option for the treatment of uncomplicated P. falciparum malaria. TRIAL REGISTRATION: NCT00393679; Pan African Clinical Trials Registry PACTR2009010000911750 Please see later in the article for the Editors' Summary. en
dc.language English en
dc.subject Protozoal diseases en
dc.subject Malaria en
dc.subject Plasmodium falciparum en
dc.subject Vectors en
dc.subject Mosquitoes en
dc.subject Anopheles en
dc.subject Treatment en
dc.subject Children en
dc.subject Comparison en
dc.subject Artemisinin combination therapies (ACT) en
dc.subject ACT en
dc.subject Clinical trials en
dc.subject Amodiaquine en
dc.subject Artesunate en
dc.subject Dihydroartemisinin-piperaquine en
dc.subject Artemether-lumefantrine en
dc.subject Chlorproguanil en
dc.subject Dapsone en
dc.subject Efficacy en
dc.subject Recurrence en
dc.subject Burkina Faso en
dc.subject Gabon en
dc.subject Nigeria en
dc.subject Rwanda en
dc.subject Uganda en
dc.subject Zambia en
dc.subject Mozambique en
dc.subject Africa, West en
dc.subject Africa, Central en
dc.subject Africa, East en
dc.subject Africa, Southern en
dc.title A head-to-head comparison of four artemisinin-based combinations for treating uncomplicated malaria in African children: a randomized trial en
dc.type Article-E en
dc.citation.issue 11 en
dc.citation.jtitle PLoS Medicine en
dc.citation.volume 8 en
dc.citation.pages e1001119 en
dc.contributor.corpauthor The Four Artemisinin-Based Combinations (4ABC) Study Group en
dc.citation.jabbreviation PLoS Med en

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