Chlorproguanil/dapsone for the treatment of non-severe Plasmodium falciparum malaria in Kenya: a pilot study.
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.
Watkins
W M
WM
Biomedical Sciences Research Centre, Kenya Medical Research Institute, (KEMRI), Nairobi.
Brandling-Bennett
A D
AD
Nevill
C G
CG
Carter
J Y
JY
Boriga
D A
DA
Howells
R E
RE
Koech
D K
DK
D000818:Animals; D003622:Dapsone / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006801:Humans; D007630:Kenya; D008288:Malaria / Q000188:drug therapy*; D010865:Pilot Projects; D010963:Plasmodium falciparum; D002727:Proguanil / Q000031:analogs & derivatives* / Q000627:therapeutic use
C007030:chlorproguanil; D003622:Dapsone; D002727:Proguanil