Artemisinin-based combination
therapies (ACTs) are the cornerstone for the treatment of
malaria. However, confirmed resistance to
artemisinins in South-East Asia, and reports of reduced efficacy of ACTs raise major concerns for
malaria treatment and control. Without new drugs to replace
artemisinins, it is essential to define dosing strategies that maximize therapeutic efficacy, limit the spread of resistance, and preserve the clinical value of ACTs. It is important to determine the extent to which reduced efficacy of ACTs reflects true resistance versus sub-optimal dosing, and quantify other factors that determine treatment failure. Pooled analyses of individual patient data from multiple clinical trials, by investigators in the Worldwide
Antimalarial Resistance Network, have shown high overall efficacy for three widely used ACTs,
artemether-lumefantrine,
artesunate-
amodiaquine, and
dihydroartemisinin-
piperaquine. Analyses also highlight that suboptimal dosing leads to increased risk of treatment failure, especially among children. In the most recent study, an analysis of clinical trials of
artesunate-
amodiaquine, widely used among children in Africa, revealed a superior efficacy for fixed-dose combination
tablets compared to loose non-fixed dose combinations. This highlights the benefits of fixed-dose combinations as a practical strategy for ensuring optimal
antimalarial dosing and maximizing efficacy. Please see related article: http://www.biomedcentral.com/1741-7015/13/66.