Halofantrine for the treatment of mefloquine chemoprophylaxis failures in Plasmodium falciparum infections.

Thai soldiers who became slide-positive for malaria while receiving mefloquine chemoprophylaxis were treated with halofantrine to study its efficacy against mefloquine-resistant falciparum malaria. Thirty-two patients received three doses of 500 mg (1,500 mg total) of halofantrine at six-hr intervals, and were then observed for four weeks. Parasite recrudescence following treatment (median 21 days) occurred in seven of 23 patients (30%) who had mefloquine serum concentrations indicative of regular prophylaxis (greater than 500 ng/ml). Serum concentrations of mefloquine in all 32 patients averaged 950 ng/ml (range 26-2,515) prior to halofantrine treatment. The halofantrine serum concentrations were higher in patients cured by halofantrine than in patients with drug failure, but this was not statistically significant. Patients who were cured by halofantrine had parasites that were more sensitive in in vitro testing to mefloquine (mean [inhibitory concentration] IC50 = 12.5 ng/ml) than in patients whose parasitemias recrudesced (mean IC50 = 23.8 ng/ml) (P less than 0.01, by Wilcoxon rank sum test). These observations suggest that the current formulation and regimen of halofantrine are not optimal for the treatment of multiple drug-resistant falciparum malaria from Thailand.

Proguanil/sulfamethoxazole malaria chemoprophy-laxis on the Thai-Cambodian border.

383 Thai soldiers on the Thai-Cambodian border were entered into a randomized malaria chemoprophylactic trial. Proguanil (200 mg/day) combined with sulfamethoxazole (1000 or 1500 mg/day) were compared to a standard combination of weekly pyrimethamine/dapsone (Maloprim). Men receiving proguanil/sulfamethoxazole had a significantly lower malaria attack rate than those taking pyrimethamine/dapsone. This was true of both the first five-week phase in which 1000 mg of sulfamethoxazole was used (0.11 vs 0.26; p less than 0.001) and in the second ten weeks in which 1500 mg of sulfamethoxazole was used (0.13 vs 0.30; p less than 0.001). Combined relative efficacy indicated that proguanil/sulfamethoxazole was better than pyrimethamine/dapsone by 64% for Plasmodium vivax and by 38% for P. falciparum. Unenforced compliance as measured by returned pills was greater than 86% in both groups. No serious drug side-effects were observed. Proguanil/sulfamethoxazole may represent a useful chemoprophylactic option in areas of multiple drug-resistant malaria.

Malaria prophylaxis with doxycycline in soldiers deployed to the Thai-Kampuchean border.

A battalion of Royal Thai Marine militia was assigned to take either 50 mg or 100 mg of doxycycline daily or pyrimethamine/dapsone weekly for malaria prophylaxis on the Thai-Kampuchean border for a 17 week period. Attack rates for the groups expressed as cases/100 men were 34 for 50 mg doxycycline, 18 for 100 mg doxycycline, and 52 for pyrimethamine/dapsone. The relative efficacy of the two doxycycline regimens compared to Maloprim were 1.6 and 1.4. Compliance with the daily drug nearly equalled that of the weekly regimen. This suggests that 100 mg of doxycycline daily can be effectively used for malaria prophylaxis by soldiers under operational conditions on the Thai-Kampuchean border.