ABSTRACT
Increasing Plasmodium falciparum resistance to chloroquine in sub-Saharan Africa necessitates use of alternative antimalarial agents. Affordable alternative treatments inlude sulfadoxine/pyrimethamine and amodiaquine. Combination of antimalarial agents can increase thepeutic resistance. We compared the efficacy of sulfadoxine/pryrimethamine; amodiaquine; and an amodiaquine/sulfadoxine/pyrimethamine combination for treatment of uncomplicated malaria in a region of high chloroquine resistance. Methods: Patients with symptoms of uncomplicated falciparum malaria and confirmed disease in Kampala; Uganda; were randomly assigned to receive sulfadoxine/pyrimethamine) plus placebo; amodiaquine (25mg/kg) sulfadoxine and 1.25mg/kg prymethamine) plus placebo; or amodiaquine plus sulfadoxine/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 completed 14 days of follow-up. Treatment failure based on clinical criteria occurred in 13 of 131 (10) patients on sulfadoxine/pyrimethamine. Based on parasitological criteria; treatment failed in 26; 16; and 10of these patients; respectively. Amodiaquine/sulfadoxine/pyrimethamine was significantly more effective than sulfadoxine/pyrimethamine alone in children aged younger than 5 years (clinical failure in 3.5vs 13.9; respectively; risk difference 10.4[95CI; 1.6-19.3] p=0.021; parasitological failure in 12.8vs 26.4; risk difference 13.61.2-26.0] p=0.041) Interpretation Sulfadoxine/pyrimethamine; amodiaquine; and amodiaquine/sulfadoxine/pyrimethamine were all effective for treatment of uncomplicated falciparum malaria in Uganda. The amodiaquine/sulfadoxine/pyrimethamine combination was the most effective; and could be the optimum low-cost alternative to chloroquine in Africa