A RANDOMIZED TRIAL OF CHLOROQUINE, AMODIAQUINE AND PYRIMETHAMINE-SULFADOXINE IN GAMBIAN CHILDREN WITH UNCOMPLICATED MALARIA

The increasing occurrence of chloroquine-resistant Plasmodium falcipar um in sub-Saharan Africa makes it essential to reconsider current reco mmendations for the treatment of uncomplicated P. falciparum malaria. In an open, randomized trial, we have compared chloroquine (CQ), amodi aquine (AQ), and pyrimethamine-sulphadoxine (PS) in rural Gambian chil dren with uncomplicated P. falciparum malaria. Three hundred children were randomly assigned at the time of consultation (D0) to oral treatm ent with 25 mg/kg CQ, 25 mg/kg AQ (bath given over 3 days), or 1.25/25 mg/kg PS. They were reviewed on day 7 (D7) and day 28 (D28) for sympt oms, malaria parasitaemia, and packed cell volume (PCV). Significantly more children treated with PS compared to CQ (17 vs 7%, P=0.03) or AQ (17 vs 3%, P=0.001) returned with clinical complaints during the firs t 3 days after treatment. Five of these patients had a generalized con vulsion (1 from the AQ group, 4 from the PS group), of whom 4 develope d cerebral malaria. At D7, significantly more patients treated with CQ compared to AQ (25 vs 7%, P=0.0009) or PS (25 vs 4%, P=0.0001) were p arasitaemic. By D28, the cumulative number of parasitological failures was significantly higher in the CQ group compared to the AQ group (65 vs 35%, P=0.0001), and significantly higher in the AB group compared to the PS group (35 vs 14%, P=0.001). Overall, 91% of parasitological failures observed during the study period were symptomatic and were co nsequently treated with an alternative antimalarial drug. Over the 28- day study period the mean PCV increased significantly less in the CQ g roup than in the PS group (1.2 vs 3.8%, P=0.016) and was lower in the CQ group than in the AQ group (1.2 vs 2.7%, P=0.12, not significant). These results suggest that PS acts more slowly than 4-aminoquinolines in controlling the clinical features of malaria, and that AQ can be co nsidered as an interim alternative to CQ in the first-line therapy of uncomplicated malaria in African areas of high CQ resistance.