Proguanil Plus Sulfamethoxazole is not Causally Prophylactic in the Macaca mulatta—Plasmodium cynomolgi Model

G. Dennis ShanksDepartments of Medicine, Immunology, Veterinary Medicine, and Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand

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Michael D. EdsteinDepartments of Medicine, Immunology, Veterinary Medicine, and Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand

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A. Lee ChedesterDepartments of Medicine, Immunology, Veterinary Medicine, and Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand

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C. Dahlem SmithDepartments of Medicine, Immunology, Veterinary Medicine, and Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand

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Kevin D. CorcoranDepartments of Medicine, Immunology, Veterinary Medicine, and Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand

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Montip NgampochjanaDepartments of Medicine, Immunology, Veterinary Medicine, and Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand

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Pranee HansukjariyaDepartments of Medicine, Immunology, Veterinary Medicine, and Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand

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Jetsumon SattabongkotDepartments of Medicine, Immunology, Veterinary Medicine, and Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand

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H. Kyle WebsterDepartments of Medicine, Immunology, Veterinary Medicine, and Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand

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New drugs for causal prophylaxis of malaria are needed. A proguanil/sulfamethoxazole combination was investigated using a rhesus monkey model (Macaca mulatta infected with Plasmodium cynomolgi) to determine whether 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 extended prepatent period (median 40 days). Two control animals became infected on days 9 and 23 following sporozoite inoculation. Plasma concentrations indicated that proguanil and sulfamethoxazole were adequately absorbed and metabolized to cycloguanil and N4-acetylsulfamethoxazole, respectively. Analysis of liver biopsy specimens demonstrated that the drugs were present two days following sporozoite inoculation but were not detectable one week later. Proguanil plus sulfamethoxazole does not eliminate exoerythrocytic-stage parasites in the rhesus monkey-P. cynomolgi model.

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