Malaria chemoprophylaxis using proguanil/dapsone combinations on the Thai-Cambodian border.

The Thai-Cambodian border is a difficult area in which to provide adequate malaria chemoprophylaxis because of multiple drug-resistant Plasmodium falciparum. In 1990-1991, Thai soldiers were randomly selected to receive proguanil (200 mg/day) combined with dapsone (4 mg or 12.5 mg/day) (n = 184) or pyrimethamine/dapsone (12.5 mg and 100 mg/week) (n = 177). Doxycycline (100 mg/day) was given to men with glucose-6-phosphate dehydrogenase deficiency (n = 77). Falciparum malaria attack rates were the same whether proguanil/dapsone (10.3%) or pyrimethamine/dapsone (11.3%) was used. However, proguanil/dapsone was more effective than pyrimethamine/dapsone in preventing vivax malaria (1.6% versus 12.4%). Men receiving doxycycline had falciparum malaria (3.9%) and vivax malaria (1.3%) at low rates. Adjusting the dapsone component from 4 mg to 12.5 mg did not improve the prophylactic effectiveness. Hematologic toxicity was not observed with the proguanil/dapsone combination. We conclude that proguanil/dapsone is not a useful alternative for malaria chemoprophylaxis on the Thai-Cambodian border.

Mefloquine chemoprophylaxis of soldiers on the Thai-Cambodian border.

Chemoprophylaxis of malaria on the Thai-Cambodian border is difficult due to the high level of drug resistance. Thirteen separate companies of Royal Thai Marine Militia were placed on 250 mg weekly mefloquine chemoprophylaxis from August 1989 to January 1990. A mean number of 722 soldiers received two or more doses of mefloquine per month for the five month study. The medication was well tolerated and compliance averaged 91%. Substantial numbers of prophylaxis breakthroughs were seen which resulted in 3.2 cases of malaria/100 man-months. Sixty-eight falciparum malaria cases were documented in men who had taken at least two mefloquine doses in the previous four weeks. No serious neuropsychiatric reactions occurred. Mefloquine chemoprophylaxis failures exist on the Thai-Cambodian border and are one sign of the spread of mefloquine resistance.

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.