SynthesisMalaria journal2026
The effect of mefloquine dose on outcome of uncomplicated falciparum malaria treated with artesunate-mefloquine: a WWARN systematic review and individual patient data meta-analysis.
Synthesis in Malaria journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
introductionA combination of mefloquine associated with artesunate (AS-MQ) was the first artemisinin-based combination therapy (ACT) to be used widely for acute uncomplicated P. falciparum malaria.
methodsIndividual patient data from 31 studies of patients with uncomplicated falciparum malaria treated with various AS-MQ regimens (target mefloquine dose 25 mg/kg), conducted in Asia, Africa and South America, were pooled and analysed to investigate the effects of MQ mg/kg dosing on malaria recurrence and other clinical, parasitological and tolerability endpoints.
resultsA total of 6,761 patients were enrolled in clinical studies conducted between 1995 and 2018; the majority (74%) were from Asia. The median age of study participants was 18 years (interquartile range IQR 8-30 years), of whom 13.5% (915/6761) were aged less than 5 years old. Participants received an estimated median [range] total mg/kg dose of mefloquine and artesunate of 25 [6.8-60] and 12 [3.6-33.3] respectively, and 1,572 (23.4%) participants were treated with the coformulation. The PCR-corrected recrudescence rate 42 days after any ASMQ treatment was 2.4% for patients enrolled in Asia and 2.5% in Africa, before artemisinin resistance emerged. Corresponding rates in children aged 1 to < 5 years were 2.9% and 3.3%. After adjusting for background artemisinin resistance, the hazard of recrudescence was higher in children aged 1 to < 5 years than in adults in Asia, but not in Africa (Asia, HR 3.01, 95%CI 1.60-5.64, p < 0.001; Africa HR 5.18, 95% CI 0.61-44.28, p = 0.133). There was only one recrudescent infection in South America. A significant MQ dose-effect was observed in Asia in patients treated with 3-dose regimens (AHR 0.89, 95% CI 0.83-0.96, p = 0.003 for 1 mg/kg increase in dose). Vomiting rates within an hour of dosing were highest in children 1- 5 years of age (n = 140) at 3.4% doses (13/378) compared to 1.7% (20/1,168) in children 5-11 years (n = 476), and 1.1% (47/4,191) in patients 12 years of age or older (n = 2027) (p < 0.001, test for trend).
conclusionAS-MQ administered over three days is a highly efficacious ACT in low to moderate transmission areas without artemisinin resistance. While further optimisation of the mefloquine dose in the coformulation in children aged 1-5 years could be considered, dose-related early vomiting is highest in this age group and may preclude this.
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