Optimising operational use of artesunate-mefloquine: a randomised comparison of four treatment regimens

A randomised trial was conducted in adults and children (> 1 year old) with acute falciparum malaria in Western Myanmar to compare the operational effectiveness of 4 different artesunate-mefloquine combinations. All regimens were well tolerated. During 42 days follow-up polymerase chain reaction genotyping-confirmed recrudescence occurred in 11 of 187 (5.9%) patients who received observed single low-dose mefloquine (15 mg/kg) and artesunate (4 mg/kg), 7 of 192 (3.6%) patients following observed single high-dose mefloquine (25 mg/kg) and artesunate (4 mg/kg), 7 of 180 (3.9%) patients following observed artesunate 4 mg/kg on day 0 plus self-administered mefloquine 15 mg/kg on day 1 and 10 mg/kg on day 2 with artesunate 4 mg/kg/day on day 1 and 2, and none of 177 patients who received this 3 d regimen under direct observation (P = 0.01). Compared with 3 d treatment regimens, single dose treatments were followed by significantly more P vivax infections during the 42 d follow-up (P = 0.009). Post treatment anaemia (haemoglobin < 10 g/dL) was reduced by the 3 d regimens. Gametocyte appearance was low with all 4 regimens. Single dose observed mefloquine-artesunate regimens were very effective, but the 3 d artesunate-mefloquine regimen is the best treatment for acute falciparum malaria in Western Myanmar. Active measures to ensure absorption and improve adherence will be necessary to realise this advantage operationally.