Combination atovaquone and proguanil hydrochloride vs. halofantrine for treatment of acute Plasmodium falciparum malaria in children

Malaria is a major cause of pediatric mortality in sub-Saharan Africa. Worldwide estimates of mortality among children with Plasmodium falciparum malaria range from 1 to 2 million deaths per year. Management of malaria is increasingly difficult because of the global spread of drug-resistant strains of P. falciparum. There is an urgent need for safe and effective new therapies to treat multidrug-resistant malaria.This open label, randomized trial compared atovaquone and proguanil hydrochloride with halofantrine for treatment of acute, uncomplicated P. falciparum malaria in children age 3 to 12 years (84 patients per group). Study drug dosages were adjusted by weight (approximately 20 and 8 mg/kg daily for three doses for atovaquone and proguanil hydrochloride and 8 mg/kg every 6 h for three doses for halofantrine). Patients were monitored by serial clinical and laboratory assessments for 28 days after starting treatment.Both regimens were effective (cure rate, 93.8% for atovaquone and proguanil hydrochloride and 90.4% for halofantrine) and produced prompt defervescence. Mean parasite clearance times were 50.2 h for halofantrine and 64.9 h for atovaquone and proguanil hydrochloride. More adverse experiences were reported in children treated with halofantrine (119) than with atovaquone and proguanil hydrochloride (73).In Kenyan children the combination of atovaquone and proguanil hydrochloride has efficacy comparable with that of halofantrine for treatment of acute uncomplicated multidrug-resistant falciparum malaria and is associated with a lower rate of adverse events.