Efficacies of mefloquine alone and of artesunate followed by mefloquine, for the treatment of uncomplicated, Plasmodium falciparum malaria in eastern Sudan

In late 2003, the efficacies of mefloquine monotherapy and of an artesunate-mefloquine combination, for the oral treatment of uncomplicated, Plasmodium falciparum malaria, were investigated and compared in New Halfa, in eastern Sudan. Of the patients who completed the 28 days of follow-up, 40 were treated only with single-dose mefloquine (at a dose of 25 mg/kg), and 38 with artesunate (at 4 mg/kg. day) for 3 days followed by single-dose mefloquine (at 15 mg/kg), given on the third day. Compared with those given the combination, the patients given mefloquine alone were more likely to suffer nausea, vomiting and dizziness (25.0% v. 2.6%; P=0.005) and to be found gametocytaemic (12.5% v. 0%; P=0.02) after treatment, and more likely to be found febrile (i.e. with a temperature >37.5 degrees C) on day 2 (25.0% v. 2.6%; P=0.005), although no patients were found febrile on day 3. Six of the patients - three (7.5%) of those given mefloquine only and three (7.9%) of those given the combination (P>0.05) - appeared to be treatment failures. Parasite genotyping indicated, however, that, although five of these six patients had true recrudescences, one (who had been treated with the combination) had been re-infected during the follow-up. The true frequencies of cure were therefore 92.5% after mefloquine alone and 94.7% after the combination (P>0.05). Thus, although the treatments appeared equally effective in clearing parasitaemias, the combination was better at clearing gametocytaemias and was less likely to cause adverse side-effects. It remains unclear why mefloquine given alone was almost 10-fold more likely to trigger adverse effects than treatment with a combination that contained the same drug. This may be a reflection of the different mefloquine doses and, for the patients given the combination, of the use of artesunate before the mefloquine treatment.