title: Poor efficacy of antimalarial biguanide-dapsone combinations in the treatment of acute, uncomplicated, falciparum malaria in Thailand.
abstract: 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 ether 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 6 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 chlorproguanil is ineffective for the treatment of falciparum malaria in Thailand.
authors.affiliation: Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Thailand.
authors.forename: P
authors.initials: P
authors.lastname: Wilairatana
authors.forename: D E
authors.initials: DE
authors.lastname: Kyle
authors.forename: S
authors.initials: S
authors.lastname: Looareesuwan
authors.forename: K
authors.initials: K
authors.lastname: Chinwongprom
authors.forename: S
authors.initials: S
authors.lastname: Amradee
authors.forename: N J
authors.initials: NJ
authors.lastname: White
authors.forename: W M
authors.initials: WM
authors.lastname: Watkins
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D003622:Dapsone / Q000494:pharmacology / Q000627:therapeutic use*; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D005493:Folic Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D018512:Parasitemia / Q000188:drug therapy; D010865:Pilot Projects; D010963:Plasmodium falciparum / Q000187:drug effects; D002727:Proguanil / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D013785:Thailand; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D005493:Folic Acid Antagonists; C007030:chlorproguanil; D003622:Dapsone; D002727:Proguanil