Atovaquone and proguanil versus pyrimethamine sulfadoxine for the treatment of acute falciparum malaria in Zambia

Atovaquone and proguanil hydrochloride are blood schizonticides that demons trate in vitro synergy against drug-resistant strains of Plasmodium falcipa rum. When coadministered, they may therefore be effective for the treatment of malaria in regions where there is known or suspected drug resistance. I n an open-label, randomized, parallel-group, clinical trial conducted in Za mbia, 163 patients (age range, 14 to 54 years) with acute P falciparum mala ria were randomly assigned to receive treatment with atovaquone and proguan il hydrochloride (1000 and 400 mg, respectively, administered orally at 24- hour intervals for 3 doses; n = 82) or pyrimethamine/sulfadoxine (75/1500 m g administered orally as a single dose; n = 81). Efficacy was assessed by c ure rate (the percentage of patients in whom parasitemia was eliminated and did not recur during 28 days of follow-up), parasite clearance time (PCT), and fever clearance time (FCT). Safety was determined by sequential clinic al and laboratory assessments over 28 days. Cure rates did not differ signi ficantly between patients treated with atovaquone and proguanil (100%) and those treated with pyrimethamine/sulfadoxine (98.8%). Patients in the atova quone and proguanil group had a significantly shorter FCT than patients in the pyrimethamine/sulfadoxine group (mean, 30.4 vs 44.9 hours; P < 0.05) bu t a longer PCT (mean, 63.0 vs 51.4 hours; P < 0.05). Both treatments were w ell tolerated; adverse events and laboratory abnormalities were typical of those normally observed in patients with malaria. In this study, the combin ation of atovaquone and proguanil was equally effective and as well tolerat ed as pyrimethamine/sulfadoxine for the treatment of acute, uncomplicated, drug-resistant falciparum malaria in Zambia.