Randomised trial of artesunate and mefloquine alone and in sequence for acute uncomplicated falciparum malaria

Abstract

The increasing frequency of therapeutic failures in falciparum malaria in Thailand shows an urgent need for effective drugs or drug combinations. Artesunate, a qinghaosu derivative, is effective in clearing parasitaemia rapidly, but the recrudescence rate can be as high as 50%. We have compared artesunate followed by mefloquine with each drug alone in acute, uncomplicated falciparum malaria. 127 patients were randomly assigned treatment with artesunate (600 mg over 5 days), mefloquine (750 mg then 500 mg 6 h later), or artesunate followed by mefloquine. All patients were admitted to hospital for 28 days to exclude reinfection. Cure was defined as no recrudescence during the 28 days' follow-up. The cure rates for mefloquine and artesunate alone were 81% (30/37 patients) and 88% (35/40); the combination was effective in all of 39 patients. Fever and parasite clearance times were significantly shorter in the groups that received artesunate than in the mefloquine-only group. The frequency of nausea and vomiting was slightly, but not significantly, higher among patients who received both drugs than in the other groups. The combination of artesunate followed by mefloquine is highly effective and well tolerated in patients with acute, uncomplicated falciparum malaria in Thailand.

PIP: Physicians enrolled 127 patients who were admitted to the Bangkok Hospital for Tropical Diseases in Thailand with acute, uncomplicated falciparum malaria between January-May 1991 into a randomized clinical trial of 3 oral treatments: artesunate, mefloquine, and artesunate followed by mefloquine. At the end of 28 days, 88% of patients who received only artesunate (total dose 600 mg), 81% of those who received only mefloquine (total dose 1250 mg), and all patients who received both artesunate and mefloquine were cured. Artesunate reduced the parasite count by 90% within 24 hours of 1st treatment. The 2 groups that received artesunate experienced considerably more rapid reduction in parasitemia and in fever than the group that received only mefloquine (p.002). Mefloquine was more adept than artesunate at clearing residual parasites. Mefloquine-treated patients experienced slightly more headaches and dizziness while they still had malaria than the other 2 groups. The physicians believed that these symptoms could actually have been due to the acute malaria infection. Patients who were on the sequential artesunate-mefloquine regime experienced more nausea and vomiting than the other groups, but the differences were insignificant. The combination therapy with artesunate and mefloquine was very effective and patients with acute, uncomplicated malaria tolerated it well.