Therapy of uncomplicated Falciparum malaria: A randomized trial comparing artesunate plus sulfadoxine-pyrimethamine versus sulfadoxine-pyrimethamine alone in Irian Jaya, Indonesia

Combining artesunate with existing antimalarial drugs may improve cure rate s, delay emergence of resistance, and reduce transmission. We performed a r andomized comparative trial to quantify the effect of adding artesunate to sulfadoxine-pyrimethamine in the treatment of uncomplicated falciparum mala ria in Indonesia. Using a modified 1997 World Health Organization protocol for assessment of therapeutic efficacy of antimalarial drugs, 105 patients (stratified by age/ethnic group) were randomized: 53 received artesunate or ally, 4 mg/kg of body weight, a single daily dose for three days, plus sulf adoxine-pyrimethamine orally (1.25 mg of pyrimethamine/kg of body weight), a single dose on day 0, and 52 patients received sulfadoxine-pyrimethamine alone. Six from the combination group were withdrawn from analysis, as were six of the sulfadoxine-pyrimethamine group. Treatment failure rates on day 14 were 0% in the artesunate plus sulfadoxine-pyrimethamine group and 8.7% in the sulfadoxine-pyrimethamine group (P = 0.12). Treatment failure rates on day 28 were 4.4% and 15.2%, respectively (P = 0.16). Relative risk of t reatment failure at 28 days was 0.3 (95% confidence interval [CI] = 0.1-1.3 ). Mean fever clearance time (1.3 versus 1.7 days) and mean parasite cleara nce time (1.4 versus 2.0 days) were both faster in the artesunate plus sulf adoxine-pyrimethamine group than in the sulfadoxine-pyrimethamine group (P = 0.08 and P < 0.0001, respectively). Only 20 (39.2%) of 51 patients treate d with artesunate plus sulfadoxine-pyrimethamine were still parasitemic on day I compared with 45 (86.5%) of 52 patients treated with sulfadoxine-pyri methamine alone (P = 0.000001, relative risk [RR] = 0.4, 95% CI = 0.3-0.6). Gametocyte carriage was lower following artesunate plus sulfadoxine-pyrime thamine than following sulfadoxine-pyrimethamine (RR = 0.5, 95% CI = 0.2-1. 0 on day 7 and RR = 0.5, 95% Cl = 0.2-1.1 on day 14). Mild diarrhea, rash, and itching resolved without treatment. Combined artesunate plus sulfadoxin e-pyrimethamine resulted in more rapid fever and parasite clearance, was we ll tolerated, reduced risk of treatment failure, and lowered gametocyte car riage.