Chlorocycloguanil, the active metabolite of
chlorproguanil, was synergistic in vitro with
dapsone against 2 culture-adapted Plasmodium falciparum isolates from Kenya; maximal synergy occurred at lower concentrations that it did with
pyrimethamine and
sulfadoxine. 48 children with asymptomatic P. falciparum
infections were treated with
chlorproguanil (at a target dose of 1.2 mg/kg) and
dapsone (target dose of 1.2 or 2.4 mg/kg); all were free of parasitaemia by day 7. The following numbers had recurrences on days 14, 21, and 28, respectively: 1 of 48, 7 of 47, and 7 of 40. All 39 children treated with
pyrimethamine (target dose 1.2 mg/kg) and
sulfadoxine (target dose 24 mg/kg) were cleared of
infection, while the following had recurrences on days 14, 21, and 28: 1 of 39, 2 of 38, and 2 of 36. The rate of decrease in parasitaemia was the same in the 2 groups, and there was no change in haematocrit or haemoglobin during the follow-up. The rate of recurrence in the children receiving chlorporguanil/
dapsone was higher, probably because these drugs have a much shorter clearance time than
pyrimethamine/
sulfadoxine.
Chlorproguanil/dapsone is an effective combination for treating P.
falciparum malaria and deserves further study.