Inadequacy of chlorproguanil 20 mg per week as chemoprophylaxis for falciparum malaria in Kenya

Abstract

After treatment with chloroquine and pyrimethamine/sulfadoxine, 118 school children aged 6 to 10 years living near the Kenyan coast were enrolled in a malaria chemoprophylaxis study and followed up for 20 weeks. Children were randomly assigned to receive either chlorproguanil 20 mg weekly (n = 78) or placebo (n = 37). The attack rate of Plasmodium falciparum infection was 42% in chlorproguanil recipients (39.8 episodes per 1000 person-weeks of prophylaxis) and 73% in placebo recipients (69.2 episodes per 1000 person-weeks, p less than 0.02). Sensitivity tests on 36 isolates successfully cultured in vitro showed that all 21 isolates from chloroproguanil recipients were resistant to dihydrofolate-reductase inhibitors, whereas only 3 of 15 isolates from the placebo group were resistant (p less than 10(-6)). Chlorproguanil in a weekly adult dose of 40 mg does not provide adequate prophylaxis against P falciparum in Kenya, probably because drug levels between doses fall below those required to suppress parasites resistant to dihydrofolate-reductase inhibitors.