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Volume 91, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the chloroquine resistance transporter () and multidrug resistance 1 () genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in and and clinically relevant outcomes after treatment with AL or ASAQ. Presence of the gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval = 2.29 – 9.78, < 0.001) and increased copy number (adjusted hazards ratio = 6.52, 95% confidence interval = 2.36–17.97, < 0.001 were significant independent risk factors for recrudescence in patients treated with AL. AL and ASAQ exerted opposing selective effects on single-nucleotide polymorphisms in and Monitoring selection and responding to emerging signs of drug resistance are critical tools for preserving efficacy of artemisinin combination therapies; determination of the prevalence of at least K76T and N86Y should now be routine.

[open-access] This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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  • Received : 14 Jan 2014
  • Accepted : 22 Apr 2014

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