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Causal Prophylactic and Radical Curative Activity of WR182393 (A Guanylhydrazone) against Plasmodium Cynomolgi in Macaca Mulatta
Kevin D. Corcoran
Kevin D. Corcoran
Departments of Veterinary Medicine, Medical Entomology, Immunology and Parasitology, and Medicine, Armed Forces Research Institute of Medical Sciences, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Bangkok, Thailand
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Pranee Hansukjariya
Pranee Hansukjariya
Departments of Veterinary Medicine, Medical Entomology, Immunology and Parasitology, and Medicine, Armed Forces Research Institute of Medical Sciences, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Bangkok, Thailand
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Jetsumon Sattabongkot
Jetsumon Sattabongkot
Departments of Veterinary Medicine, Medical Entomology, Immunology and Parasitology, and Medicine, Armed Forces Research Institute of Medical Sciences, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Bangkok, Thailand
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Montip Ngampochjana
Montip Ngampochjana
Departments of Veterinary Medicine, Medical Entomology, Immunology and Parasitology, and Medicine, Armed Forces Research Institute of Medical Sciences, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Bangkok, Thailand
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Michael D. Edstein
Michael D. Edstein
Departments of Veterinary Medicine, Medical Entomology, Immunology and Parasitology, and Medicine, Armed Forces Research Institute of Medical Sciences, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Bangkok, Thailand
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C. Dahlem Smith
C. Dahlem Smith
Departments of Veterinary Medicine, Medical Entomology, Immunology and Parasitology, and Medicine, Armed Forces Research Institute of Medical Sciences, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Bangkok, Thailand
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G. Dennis Shanks
G. Dennis Shanks
Departments of Veterinary Medicine, Medical Entomology, Immunology and Parasitology, and Medicine, Armed Forces Research Institute of Medical Sciences, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Bangkok, Thailand
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Wilbur K. Milhous
Wilbur K. Milhous
Departments of Veterinary Medicine, Medical Entomology, Immunology and Parasitology, and Medicine, Armed Forces Research Institute of Medical Sciences, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Bangkok, Thailand
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Primaquine is the only currently available drug effective against persistent tissue stages of relapsing malaria in humans. Causal prophylactic and radical curative properties of WR182393 (a guanylhydrazone) were investigated as part of an effort to evaluate alternatives to primaquine in the rhesus monkey (Macaca mulatta)/Plasmodium cynomolgi test model. The drug was suspended in dimethylsulfoxide for intramuscular (im) injection. A pilot study indicated causal prophylactic activity in a regimen of 40 mg base/kg/day im for three days beginning the day before intravenous challenge with 1 × 106 P. cynomolgi sporozoites. Regimens of 31, 10, 3.1, and 0 mg base/kg/day im for three days were then tested in groups of two monkeys given a similar challenge. The two animals given 31 mg base/kg/day remained parasite-free. Average time to parasitemia for the lower dosage groups was 38, 18, and 8 days respectively. Groups of two monkeys with sporozoite-induced P. cynomolgi infections were also treated for seven days with 31, 10, 3.1, and 0 mg base/kg/day im in combination with 10 mg base/kg/day of chloroquine orally. Both monkeys given 31 mg base/kg/day did not relapse. The average time to relapse following treatment was 48, 29, and 8 days, respectively, for the lower dosage groups. Compound WR182393 is the first non-8-aminoquinoline class of drug to exhibit both causal prophylactic and radical curative properties against a relapsing primate, vivax-like malaria.
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| Past two years | Past Year | Past 30 Days | |
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