RESUMEN
We conducted a double-blind, randomized, placebo-controlled trial in Sao Tome and Principe to investigate the safety, tolerability and efficacy of chloroquine (CQ) combined with artesunate (AS) over CQ monotherapy. Four hundred children, aged 6-59 months, with acute uncomplicated Plasmodium falciparum malaria were randomized to receive a standard dose of CQ (25 mg/kg bodyweight) over 3 d or CQ + AS (4 mg/kg bodyweight) daily for 3 d. Children were followed-up for 28 d. The combined treatment was well tolerated and there were no serious drug-related adverse events. By day 2 parasite clearance was significantly faster for children treated with CQ + AS compared with CQ alone (29/194 [14.9%] vs. 168/190 [88.4%] still parasitaemic, P< 0.0001). Day 14 parasitological failure rates were 153/191 (80.1%) for CQ alone compared with 32/193 (16.6%) in the CQ + AS group (odds ratio [OR] =20.2, 95% CI 11.7-35.4, P< 0.001). Corresponding clinical failure rates were 128/161 (67.0%) and 12/193 (6.2%) (OR = 30.6, 95% CI 15.3-62.7, P< 0.001). By day 28 the parasitological failure rates (new infections excluded) were 155/191 (81.1%) in the CQ group and 63/194 (32.4%) in the CQ + AS group (OR = 8.9, 95% CI 5.4-14.7, P< 0.001). Symptoms resolved faster in children who received AS. They were also less likely to be gametocytaemic after treatment. The combination treatment was well tolerated and considerably improved treatment efficacy. However, the current levels of CQ resistance preclude its use in Sao Tome where CQ should be abandoned as first-line drug. However, CQ + AS may be an option in areas where CQ resistance is lower.