PROGUANIL PLUS SULFAMETHOXAZOLE IS NOT CAUSALLY PROPHYLACTIC IN THE MACACA-MULATTA PLASMODIUM-CYNOMOLGI MODEL

New drugs for causal prophylaxis of malaria are needed. A proguanil/su lfamethoxazole combination was investigated using a rhesus monkey mode l (Macaca mulatta infected with Plasmodium cynomolgi) to determine whe ther causal prophylaxis could be achieved. When a five-day regimen of proguanil (40 mg/kg/day) combined with sulfamethoxazole (100 mg/kg/day ) was used, infection of all animals (6 of 6) was observed, with an ex tended prepatent period (median 40 days). Two control animals became i nfected on days 9 and 23 following sporozoite inoculation. Plasma conc entrations indicated that proguanil and sulfamethoxazole were adequate ly absorbed and metabolized to cycloguanil and N-4-acetylsulfamethoxaz ole, respectively. Analysis of liver biopsy specimens demonstrated tha t the drugs were present two days following sporozoite inoculation but were not detectable one week later. Proguanil plus sulfamethoxazole d oes not eliminate exoerythrocytic-stage parasites in the rhesus monkey -P. cynomolgi model.