A randomized comparison of chloroquine, amodiaquine and their combination with pyrimethamine-sulfadoxine in the treatment of acute, uncomplicated, Plasmodium falciparum malaria in children.

Abstract

The increasing resistance of Plasmodium falciparum to antimalarial monotherapy (MT) has created an urgent need for the evaluation of alternative effective, safe, cheap, readily available and affordable, combination treatments (CT) with antimalarial drugs. In the present study, the efficacies of chloroquine (CQ) or amodiaquine (AQ) in the oral treatment of acute, symptomatic, uncomplicated, Plasmodium falciparum malaria were compared with those of oral treatments with the combination of CQ or AQ with pyrimethamine-sulfadoxine (PS). The CQ and AQ were each given at a dose of 10 mg/kg.day for 3 days (days 0, 1 and 2), with or without PS given as a single dose (25 mg sulfadoxine/kg) at presentation (day 0). Overall, 303 children aged 0.5-10 years (74 given CQ, 82 AQ, 72 CQPS and 75 AQPS) were evaluated. The fever-clearance time (FCT) was significantly shorter in those treated with AQPS than in those treated with CQ or CQPS. The proportions of patients with complete clearance of their parasitaemias on days 1 and 2 were significantly larger and the parasite-clearance times (PCT) were all significantly shorter with the drug combinations than with their corresponding MT. For example, the mean (S.D.) PCT were 2.6 (0.8) days for CQ v. 2.1 (0.8) days for CQPS (P=0.0002), and 2.6 (0.7) days for AQ v. 2.1 (0.7) days for AQPS (P=0.00001). The cure 'rates' on days 14, 21 and 28 were also significantly higher with AQ, CQPS and AQPS than with CQ; those on day 28, for example, were 47.2%, 98.7%, 100% and 100% for CQ, AQ, CQPS and AQPS, respectively (P=0.000001). Gametocyte carriages on day 3 or on days 3, 7 and/or 14 combined were significantly lower in those treated with CQPS than in those given CQ; there was no gametocyte carriage in the CT groups on day 28. In the CQ group, eight of 13 children with gametocytaemia on day 3 had a response indicative of resistance. However, the five CQ-resistant infections that were re-treated with AQPS responded promptly, with a PCT significantly shorter than that during the initial treatment with CQ and with a cure 'rate' of 100% on day 28. Adverse reactions to treatment were similar on the first and subsequent days of treatment and were tolerable except for pruritus, which was significantly more common in children treated with CQ alone than in the other treatment groups. Haematological and biochemical parameters were not adversely affected by any treatment. The CQPS and AQPS combinations appear to be well tolerated and may be useful as alternatives to monotherapy with CQ or AQ as resistance to the single drugs develops.