Atovaquone plus proguanil versus halofantrine for the treatment of imported acute uncomplicated Plasmodium falciparum malaria in non-immune adults: Arandomized comparative trial

In endemic zones, the atovaquone-proguanil (AP) combination is well tolerat ed and effective in treating acute, uncomplicated malaria. Trials involving non-immune patients are lacking, however. We conducted a randomized, multi center open-label trial to determine the efficacy and tolerability of the A P combination (1,000 mg + 400 mg once daily for 3 days) in comparison with halofantrine (HF) (1,500 mg in 3 doses) in non-immune adults with imported uncomplicated Plasmodium falciparum malaria. Follow-up visits were programm ed on Days 7, 14, 21, 28, and 35 after hospital discharge. Out of 48 patien ts enrolled in the study, 41 were assessable for the cure rate (21 in the A P group and 20 in the HF group). All the patients were cured. The mean para site clearance time was longer (63 +/- 23 hours) in the AP group than in th e HF group (48 +/- 15 hours) (P = 0.02). The frequency of gastrointestinal adverse events was higher in the AP group. No noteworthy electrocardiograph ic changes were observed, particularly in the QTc interval. The AP combinat ion appears to be a valuable alternative treatment in non-immune adults.