Poor efficacy of antimalarial biguanide-dapsone combinations in the treatment of acute, uncomplicated, falciparum malaria in Thailand

Combinations of dapsone with proguanil or chlorproguanil have proved effective in the treatment of chloroquine-resistant falciparum malaria in Africa and for prophylaxis in Asia. These combinations have not been used for treatment in areas with multi-drug-resistant parasites such as in Thailand. Combinations of dapsone (approximately 4 mg/kg) plus either proguanil (approximately 8 mg/kg; DP regimen; N = 10) or chlorproguanil (approximately 1.4 mg/kg; DC regimen; N= = 16) were given once a day for 3 days to adult Thai patients with acute, uncomplicated, falciparum malaria. The two regimens were well tolerated and had no side-effects, but the cure rates, assessed at 28-day follow-up, were only 10% for DP (60% with RI response and 30% with RII) and 14% for DC (29% with RI response and 57% with RII). The mean (s.d.) fever-clearance times in those patients who were cured (S) or whose infections recrudesced (RI response) were 103 (56) h for those given DP and 90 (42) h for those given DC. The corresponding parasite-clearance times were 83 (46) for DP and 53 (21) h for DC. In-vitro susceptibility testing of isolates obtained both before treatment and at recrudescence demonstrated marked resistance to cycloguanil, dapsone, chloroquine and mefloquine. The results demonstrate that short-course treatment with dapsone plus either proguanil or chloproguanil is ineffective for the treatment of falciparum malaria in Thailand.