The effect of dose on the antimalarial efficacy of artemether-lumefantrine: a systematic review and pooled analysis of individual patient data

The Lancet Infectious Diseases
Worldwide Antimalarial Resistance Network (WWARN) AL Dose Impact Study Group

Abstract

Artemether-lumefantrine is the most widely used artemisinin-based combination therapy for malaria, although treatment failures occur in some regions. We investigated the effect of dosing strategy on efficacy in a pooled analysis from trials done in a wide range of malaria-endemic settings. We searched PubMed for clinical trials that enrolled and treated patients with artemether-lumefantrine and were published from 1960 to December, 2012. We merged individual patient data from these trials by use of standardised methods. The primary endpoint was the PCR-adjusted risk of Plasmodium falciparum recrudescence by day 28. Secondary endpoints consisted of the PCR-adjusted risk of P falciparum recurrence by day 42, PCR-unadjusted risk of P falciparum recurrence by day 42, early parasite clearance, and gametocyte carriage. Risk factors for PCR-adjusted recrudescence were identified using Cox's regression model with frailty shared across the study sites. We included 61 studies done between January, 1998, and December, 2012, and included 14,327 patients in our analyses. The PCR-adjusted therapeutic efficacy was 97·6% (95% CI 97·4-97·9) at day 28 and 96·0% (95·6-96·5) at day 42. After controlling for age and parasitaemia, patients prescribe...Continue Reading

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Citations

Dec 26, 2015·Malaria Journal·Sisay GetachewBeyene Petros
Sep 8, 2015·BMC Medicine·UNKNOWN WWARN Artemisinin based Combination Therapy (ACT) Africa Baseline Study GroupAmbrose O Talisuna
Apr 19, 2015·BMC Medicine·UNKNOWN WorldWide Antimalarial Resistance Network (WWARN) AS-AQ Study GroupIssaka Zongo
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