Amodiaquine, sulfadoxine/pyrimethamine, and combination therapy for treatment of uncomplicated falciparum malaria in Kampala, Uganda: a randomised trial

Background Increasing Plasmodium falciparum resistance to chloroquine in su b-Saharan Africa necessitates use of alternative antimalarial agents. Affor dable alternative treatments include sulfadoxine/pyrimethamine and amodiaqu ine. Combination of antimalarial agents can increase therapeutic efficacy a nd delay emergence of drug resistance. We compared the efficacy of sulfadox ine/ pyrimethamine, amodiaquine, and an amodiaquine/ sulfadoxine/pyrimetham ine combination for treatment of uncomplicated malaria in a region of high chloroquine resistance. Methods Patients with symptoms of uncomplicated falciparum malaria and conf irmed disease in Kampala, Uganda, were randomly assigned to receive sulfado xine/pyrimethamine (25 mg/kg sulfadoxine, and 1.25 mg/kg pyrimethamine) plu s placebo; amodiaquine (25 mg/kg) plus placebo; or amodiaquine plus sulfado xine/pyrimethamine. Patients were followed up for 14 days, and clinical and parasitological outcomes were assessed. Findings 90% (400/445) of patients enrolled in the study successfully compl eted 14 days of follow-up. Treatment failure based on clinical criteria occ urred in 13 of 131 (10%) patients on sulfadoxine/ pyrimethamine, nine of 13 1 (7%) on amodiaquine, and four of 138 (3%) on amodiaquine/sulfadoxine/pyri methamine. Based on parasitological criteria, treatment failed in 26%, 16%, and 10% of these patients, respectively. Amodiaquine/sulfadoxine/pyrimetha mine was significantly more effective than sulfadoxine/pyrimethamine alone in children aged younger than 5 years (clinical failure in 3.5% vs 13.9%, r espectively, risk difference 10.4% [95% CI, 1.6-19-3] p=0.021; parasitologi cal failure in 12.8% vs 26.4%, risk difference 13.6% [1.2-26.0] p=0.041). Interpretation Sulfadoxine/pyrimethamine, amodiaquine, and amodiaquine/sulf adoxine/pyrimethamine were all effective for treatment of uncomplicated fal ciparum malaria in Uganda. The amodiaquine/sulfadoxine/ pyrimethamine combi nation was the most effective, and could be the optimum low-cost alternativ e to chloroquine in Africa.