A randomized trial of chloroquine, amodiaquine and pyrimethamine‐sulphadoxine in Gambian children with uncomplicated malaria

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Abstract
The increasing occurrence of chloroquine‐resistant Plasmodium falciparum in sub‐Saharan Africa makes it essential to reconsider current recommendations for the treatment of uncomplicated P. falciparum malaria. In an open, randomized trial, we have compared chloroquine (CQ), amodiaquine (AQ), and pyrimethamine‐sulphadoxine (PS) in rural Gambian children with uncomplicated P. falciparum malaria. Three hundred children were randomly assigned at the time of consultation (Do) to oral treatment with 25 mg/kg CQ, 25 mg/kg AQ (both given over 3 days), or 1.25/25 mg/kg PS. They were reviewed on day 7 (D7) and day 28 (D28) for symptoms, 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 first 3 days after treatment. Five of these patients had a generalized convulsion (4 from the AQ group, 4 from the PS group), of whom 4 developed 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 parasitaemic. 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 AQ 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 consequently treated with an alternative anti‐malarial drug. Over the 28‐day study period the mean PCV increased significantly less in the CQ group 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 considered as an interim alternative to CQ in the first‐line therapy of uncomplicated malaria in African areas of high CQ resistance.