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 e ffective in the treatment of chloroquine-resistant falciparum malaria in Africa and for prophylaxis in Asia. These combinations have not bee n 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 chlorp roguanil (approximately 1.4 mg/kg; DC regimen; N = 16) were given once a day for 3 days to adult Thai patients with acute, uncomplicated, fa lciparum 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 t imes in those patients who were cured (S) or whose infections recrudes ced (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 (4 6) for DP and 53 (21) h for DC. In-vitro susceptibility testing of iso lates 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 plu s either proguanil or chloproguanil is ineffective for the treatment o f falciparum malaria in Thailand.