Comparative clinical trial of artesunate and the combination of artesunate-mefloquine in multidrug-resistant falciparum malaria

Sixty-six male Thai patients with acute uncomplicated falciparum malaria, admitted to the Bangkok Hospital for Tropical Diseases, were randomised to receive one of two regimens of artesunate. 32 patients received 300mg artesunate on the first day, followed by 100mg daily for another 4 days; 34 patients received oral artesunate at an initial dose of 200mg, followed by 100mg 12 hours later, then a single dose of 750mg mefloquine 24 hours after the initial dose of artesunate. Hospital follow-up was 28 days for artesunate alone and 42 days for the combination regimen. Seven patients were excluded from the study (1 vs 6 in the artesunate alone and the combination regimens, respectively). All patients had a rapid initial response to treatment, with a median parasite clearance time of 36.3 vs 37.1 hours and fever clearance time of 30.7 vs 24.3 hours for artesunate alone and the combination regimen, respectively. The cure rates for artesunate alone and the combination regimen were 93.6 and 78.6%, respectively. No serious adverse effects were found in any of the patients. A 24-hour short course of the combination artesunate-mefloquine used in this study is not likely to be a good alternative treatment to a 5-day regimen of oral artesunate alone. However, a grade two or three type of resistance (RII-RIII type of response) was not observed with this short-course regimen. A higher dose of mefloquine may be required for the combination regimen to secure a high cure rate. Further studies are needed.