Comparison of oral artemether and mefloquine in acute uncomplicated falciparum malaria

Abstract

Plasmodium falciparum malaria in Thailand is highly resistant to available antimalarials, and alternative drugs are needed urgently. Artemether is effective against falciparum malaria but associated with a high recrudescence rate. The proper dosage regimen remains to be defined. We have done a clinical trial comparing mefloquine 1250 mg in divided doses with oral artemether at 700 mg total dose given over 5 days in acute uncomplicated falciparum malaria. 46 patients, admitted to the Bangkok Hospital for Tropical Diseases, were randomised to receive either mefloquine (12) or artemether (34). Hospital follow-up was 28 days for the artemether group and 42 days for the mefloquine group. Oral artemether gave a significantly faster parasite clearance time than mefloquine (30 vs 64 h), and a significantly better cure rate (97 vs 64%) with fewer episodes of dizziness and vomiting. Oral artemether at 700 mg given over 5 days is effective and well tolerated. The cure rate with this regimen is higher than that reported by previous studies with 600 mg intramuscular artemether given over 5 days. Oral artemether can be considered as an alternative drug for multiple-drug-resistant falciparum malaria.

PIP: Plasmodium falciparum malaria in Thailand is resistant to available antimalarial drugs, which necessitates the search for alternative drugs. In a clinical trial mefloquine 1250 mg in divided doses was compared with oral artemether at 700 mg total dose given over 5 days in acute uncomplicated falciparum malaria. 46 adult men, aged 15-50 years and weighing 45-65 kg, with acute uncomplicated falciparum malaria, no history of liver or kidney diseases, and not history of tasking antimalarials for this episode of illness were recruited at the Bangkok Hospitak for Tropical Diseases. 12 were treated with mefloquine and 34 with oral artemether. Hospital follow-up was 28 days for the artemether group and 42 days for the mefloquine group. Parasites did not clear from the blood of 2 patients in the mefloquine group, although there was a decrease in parasitemia. The other 10 patients in the mefloquine group has a good initial response with mean parasite clearance times and fever clearance times of 64 and 27 hours respectively. Oral artemether gave a significantly faster parasite clearance time than mefloquine (30 vs. 64 hours), and a significantly better cure rate (97 vs. 64%) with fewer episodes of dizziness and vomiting. Oral artemether at 700 mg given over 5 days is effective and well tolerated. The cure rate with this regimen is higher than that reported with 600 mg intramuscular artemether given over 5 days. Mefloquine 1250 mg has a cure rate of 80-84% but it produces side effects such as vomiting. The treatment with artemether should last at least 5 days with a dose above 600 mg for a cure rate approaching 100%. This treatment is still likely to be more acceptable to patients than the combination regimen of quinine plus tetracycline for 7 days. These findings suggest that neither artemether nor mefloquine is effective against the intrahepatic stage of Plasmodium vivax. Primaquine is the choice of drug for radical cure.