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SummaryBackground-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 malariaendemic settings.Methods-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. 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 prescribed a higher dose of artemether had a lower risk of having parasitaemia on day 1 (adjusted odds ratio [OR] 0·92, 95% CI 0·86-0·99 for every 1 mg/kg increase in daily artemether dose; p=0·024), but not on day 2 (p=0·69) or day 3 (0·087). In Asia, children weighing 10-15 kg who received a total lumefantrine dose less than 60 mg/kg had the lowest PCR-adjusted efficacy (91·7%, 95% CI 86·5-96·9). In Africa, the risk of treatment failure was greatest in malnourished children aged 1-3 years (PCR-adjusted efficacy 94·3%, 95% CI 92·3-96·3). A higher artemether dose was associated with a lower gametocyte presence within 14 Findings-We included 61 studies done between Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts days of treatment (adjusted OR 0·92, 95% CI 0·85-0·99; p=0·037 for every 1 mg/kg increase in total artemether dose).Interpretation-The recommended dose of artemether-lumefantrine provides reliable efficacy in most patients with uncomplicated malaria. However, therapeutic efficacy was lowest in young children from Asia and young underweight children from Africa; a higher dose regimen should be assessed in these groups.Funding-Bill & Melinda Gates Foundation. IntroductionArtemisinin-based combination therapies are the first-line treatment for uncomplicated Plasmodium falciparum malaria in most malaria-endemic countries, 1 and they have been advocated to counter the threat of antimalarial drug resistance by delaying its emergence and spread. 2 As such, artemisinin-based combination therapies are a key component of malaria elimination efforts. 3The combination of artemether and lumefantrine was originally introduced as a four-dose regimen that proved to be efficacious in studies done in China, 4 Africa, 5 and India; 6 however, after detailed pharmacokinetic-pharmacodynamic assess...

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One hundred and ten children aged 6 months to 11 years were randomly treated with halofantrine (HF), sulfadoxine-pyrimethamine (S-P) or chloroquine (CQ) for acute uncomplicated Plasmodium falciparum malaria in an endemic area of south-western Nigeria. The response of infection to treatment in each child was monitored for 14 d. The mean fever clearance times were 1.9 d (n = 36), 1.6 d (n = 27), and 1-7 d (n = 28) for children treated with HF, S-P and CQ, respectively. The parasite clearance times were 3.4 d (n = 39), 4.4 d (n = 24) and 4.1 d (n = 15) in the 3 groups of children. The cure rate at day 7 was 92.3% (36/39) in children treated with HF, 72.7% (24/33) in those treated with S-P, and 39.5% (15/38) in those treated with CQ. By day 14, 4 of 36 (11.1%) parasitologically cured patients treated with HF had experienced recrudescences. The corresponding figures among children treated with S-P or CQ were 8.3% and 13.3%, respectively. The 3 drugs were well tolerated. The results of the study showed a further decline in the sensitivity of P. falciparum infections to CQ, while HF and S-P remained relatively effective in the treatment of malaria in south-west Nigeria.