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

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

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

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

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

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

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

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

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

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

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DOI:
https://doi.org/10.4269/ajtmh.1994.50.641
Volume/Issue:
Volume 50: Issue 5
Page(s):
641–645
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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.

Author Notes

Copyright:
Copyright © 1994 by The American Society of Tropical Medicine and Hygiene 1994
Published Online:
May 1994
Cover The American Journal of Tropical Medicine and Hygiene
The American Journal of Tropical Medicine and Hygiene
Print ISSN:
0002-9637
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