CHLORPROGUANIL-DAPSONE - EFFECTIVE TREATMENT FOR UNCOMPLICATED FALCIPARUM-MALARIA

Pyrimethamine-sulfadoxine, the first choice for uncomplicated falcipar um malaria in Africa, exerts strong selection pressure for resistance because of its slow elimination. It is likely that resistance will eme rge rapidly, and there is no widely affordable replacement. Chlorprogu anil-dapsone is cheap, rapidly eliminated, more potent than pyrimetham ine-sulfadoxine, and could be introduced in the near future to delay t he onset of antifolate resistance and as ''salvage therapy'' for pyrim ethamine-sulfadoxine failure. A total of 448 children were randomly al located (double blind) to either a single dose of pyrimethamine-sulfad oxine or to one of two chlorproguanil-dapsone regimens: a single dose or three doses at 24-h intervals. Reinfections are clinically indistin guishable from recrudescence and are more likely after treatment with rapidly eliminated drugs; we measured the incidence of parasitemia in 205 initially aparasitemic children to allow comparison with the three treatment groups. The patients and a community surveillance group wer e followed up for 28 days, At the study end point, 31.2% (95% confiden ce interval, 24.9-38.0) of the community surveillance group subjects w ere parasitemic, compared with subjects in the treatment groups, whose rates of parasitemia were 40.8% (32.9-49.0; relative risk [RR], 1.31 [0.99-1.73]) after triple-dose chlorproguanil-dapsone, 19.7% (13.5-27. 2; RR, 0.63 [0.43-0.93]) after pyrimethamine-sulfadoxine, and 65.6% (5 7.5-73.0; RR, 2.10 [1.6-2.65]) after single-dose chlorproguanil-dapson e. Pyrimethamine-sulfadoxine and triple-dose chlorproguanil-dapsone we re effective treatments, Pyrimethamine-sulfadoxine provided chemoproph ylaxis during follow-up because of its slow elimination, Triple-dose c hlorproguanil-dapsone should now be developed in an attempt to reduce the rate of emergence of antifolate resistance in Africa and for affor dable salvage therapy in cases of pyrimethamine-sulfadoxine failure.