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-
1.
Hill DR, Baird JK, Parise ME, Lewis LS, Ryan ET, Magill AJ, 2006. Primaquine: report from CDC expert meeting on malaria chemoprophylaxis I. Am J Trop Med Hyg 75: 402– 415.
-
2.
Krudsood S, Tangpukdee N, Wilairatana P, Phophak N, Baird JK, Brittenham GM, Looareesuwan S, 2008. High-dose primaquine regimens against relapse of Plasmodium vivax malaria. Am J Trop Med Hyg 78: 736– 740.
-
3.
Schmidt LH, Fradkin R, Squires W, Genther CS, 1948. Malaria chemotherapy; the response of sporozoite-induced infections with Plasmodium cynomolgi to various antimalarial drugs. Fed Proc 7: 253– 254.
-
4.
Krotoski WA, Bray RS, Garnham PC, Gwadz RW, Killick-Kendrick R, Draper CC, Targett GA, Krotoski DM, Guy MW, Koontz LC, Cogswell FB, 1982. Observations on early and late post-sporozoite tissue stages in primate malaria. II. The hypnozoite of Plasmodium cynomolgi bastianellii from 3 to 105 days after infection, and detection of 36- to 40-hour pre-erythrocytic forms. Am J Trop Med Hyg 31: 211– 225.
-
5.
Stewart VA, 2003. Plasmodium vivax under the microscope: the Aotus model. Trends Parasitol 19: 589– 594.
-
6.
Schmidt LH, 1983. Appraisals of compounds of diverse chemical classes for capacities to cure infections with sporozoites of Plasmodium cynomolgi. Am J Trop Med Hyg 32: 231– 257.
-
7.
Institute of Laboratory Animal Resources CoLS, 1996. Guide for the Care and Use of Laboratory Animals. Council CoLSotNR, ed. Washington, DC: National Academy Press.
-
8.
Hou LJ, Raju SS, Abdulah MS, Nor NM, Ravichandran M, 2004. Rifampicin antagonizes the effect of choloroquine on chloroquine-resistant Plasmodium berghei in mice. Jpn J Infect Dis 57: 198– 202.
-
9.
Pukrittayakamee S, Prakongpan S, Wanwimolruk S, Clemens R, Looareesuwan S, White NJ, 2003. Adverse effect of rifampin on quinine efficacy in uncomplicated falciparum malaria. Antimicrob Agents Chemother 47: 1509– 1513.
-
10.
Schmidt LH, 1981. Comparative efficacies of quinine and chloroquine as companions to primaquine in a curative drug regimen. Am J Trop Med Hyg 30: 20– 25.
-
11.
Sarma PSA, 1988. Tinidazole: a new drug in the treatment of vivax malaria. Current Therapeutic Res 43: 954– 956.
-
12.
Kim KA, Park JY, Lee JS, Lim S, 2003. Cytochrome P450 2C8 and CYP3A4/5 are involved in chloroquine metabolism in human liver microsomes. Arch Pharm Res 26: 631– 637.
| Past two years | Past Year | Past 30 Days | |
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| Abstract Views | 346 | 323 | 16 |
| Full Text Views | 357 | 7 | 0 |
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Use of a Rhesus Plasmodium cynomolgi Model to Screen for Anti-Hypnozoite Activity of Pharmaceutical Substances
Gregory A. Deye
Gregory A. Deye
Walter Reed Army Institute of Research, Silver Spring, Maryland; Department of Veterinary Medicine and Department of Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand
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Montip Gettayacamin
Montip Gettayacamin
Walter Reed Army Institute of Research, Silver Spring, Maryland; Department of Veterinary Medicine and Department of Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand
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Pranee Hansukjariya
Pranee Hansukjariya
Walter Reed Army Institute of Research, Silver Spring, Maryland; Department of Veterinary Medicine and Department of Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand
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Rawiwan Im-erbsin
Rawiwan Im-erbsin
Walter Reed Army Institute of Research, Silver Spring, Maryland; Department of Veterinary Medicine and Department of Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand
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Jetsumon Sattabongkot
Jetsumon Sattabongkot
Walter Reed Army Institute of Research, Silver Spring, Maryland; Department of Veterinary Medicine and Department of Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand
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Yarrow Rothstein
Yarrow Rothstein
Walter Reed Army Institute of Research, Silver Spring, Maryland; Department of Veterinary Medicine and Department of Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand
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Louis Macareo
Louis Macareo
Walter Reed Army Institute of Research, Silver Spring, Maryland; Department of Veterinary Medicine and Department of Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand
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Susan Fracisco
Susan Fracisco
Walter Reed Army Institute of Research, Silver Spring, Maryland; Department of Veterinary Medicine and Department of Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand
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Kent Bennett
Kent Bennett
Walter Reed Army Institute of Research, Silver Spring, Maryland; Department of Veterinary Medicine and Department of Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand
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Alan J. Magill
Alan J. Magill
Walter Reed Army Institute of Research, Silver Spring, Maryland; Department of Veterinary Medicine and Department of Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand
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Colin Ohrt
Colin Ohrt
Walter Reed Army Institute of Research, Silver Spring, Maryland; Department of Veterinary Medicine and Department of Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand
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There remains a need for new drugs to prevent relapse of Plasmodium vivax or P. ovale infection. The relapsing primate malaria P. cynomolgi has been used for decades to assess drugs for anti-hypnozoite activity. After sporozoite inoculation and blood-stage cure of initial parasitemia with chloroquine, rhesus macaques were treated on subsequent relapses with chloroquine in conjunction with test regimens of approved drugs. Tested drugs were selected for known liver or blood-stage activity and were tested alone or in conjunction with low-dose primaquine. Tinidazole and pyrazinamide prevented relapse when used in conjunction with chloroquine and low-dose primaquine. Triamterene and tinidazole administered without primaquine achieved radical cure in some animals. All other tested drugs or combinations failed to prevent relapse. The rhesus macaque–P. cynomolgi model remains a useful tool for screening drugs with anti-hypnozoite activity. Tinidazole and pyrazinamide require further investigation as agents to enable dose reduction of primaquine.
Author Notes
Financial support: This study was supported by the Military Infectious Disease Research Program, US Army Medical Research and Materiel Command.
Authors' addresses: Gregory A. Deye, Yarrow Rothstein, Louis Macareo, Susan Fracisco, Kent Bennett, Alan Magill, and Colin Ohrt, Walter Reed Army Institute of Research, Silver Spring, MD, E-mails: gregory.deye@gmail.com, yarrow.rothstein@us.army.mil, lmacareo@wrp-ksm.org, susan.fracisco@yahoo.com, kent.bennett@us.army.mil, alan.magill@darpa.mil, and colin.ohrt@us.army.mil. Gettayacamin Montip, Hansukjariya Pranee, and Rawiwan Im-erbsin, Department of Veterinary Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand, E-mails: montipg@AAALAC.org, praneeH@afrims.org, and RawiwanI@afrims.org. Jetsumon Sattabongkot, Department of Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand, E-mail: Jetsumon@hotmail.com.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Hill DR, Baird JK, Parise ME, Lewis LS, Ryan ET, Magill AJ, 2006. Primaquine: report from CDC expert meeting on malaria chemoprophylaxis I. Am J Trop Med Hyg 75: 402– 415.
-
2.
Krudsood S, Tangpukdee N, Wilairatana P, Phophak N, Baird JK, Brittenham GM, Looareesuwan S, 2008. High-dose primaquine regimens against relapse of Plasmodium vivax malaria. Am J Trop Med Hyg 78: 736– 740.
-
3.
Schmidt LH, Fradkin R, Squires W, Genther CS, 1948. Malaria chemotherapy; the response of sporozoite-induced infections with Plasmodium cynomolgi to various antimalarial drugs. Fed Proc 7: 253– 254.
-
4.
Krotoski WA, Bray RS, Garnham PC, Gwadz RW, Killick-Kendrick R, Draper CC, Targett GA, Krotoski DM, Guy MW, Koontz LC, Cogswell FB, 1982. Observations on early and late post-sporozoite tissue stages in primate malaria. II. The hypnozoite of Plasmodium cynomolgi bastianellii from 3 to 105 days after infection, and detection of 36- to 40-hour pre-erythrocytic forms. Am J Trop Med Hyg 31: 211– 225.
-
5.
Stewart VA, 2003. Plasmodium vivax under the microscope: the Aotus model. Trends Parasitol 19: 589– 594.
-
6.
Schmidt LH, 1983. Appraisals of compounds of diverse chemical classes for capacities to cure infections with sporozoites of Plasmodium cynomolgi. Am J Trop Med Hyg 32: 231– 257.
-
7.
Institute of Laboratory Animal Resources CoLS, 1996. Guide for the Care and Use of Laboratory Animals. Council CoLSotNR, ed. Washington, DC: National Academy Press.
-
8.
Hou LJ, Raju SS, Abdulah MS, Nor NM, Ravichandran M, 2004. Rifampicin antagonizes the effect of choloroquine on chloroquine-resistant Plasmodium berghei in mice. Jpn J Infect Dis 57: 198– 202.
-
9.
Pukrittayakamee S, Prakongpan S, Wanwimolruk S, Clemens R, Looareesuwan S, White NJ, 2003. Adverse effect of rifampin on quinine efficacy in uncomplicated falciparum malaria. Antimicrob Agents Chemother 47: 1509– 1513.
-
10.
Schmidt LH, 1981. Comparative efficacies of quinine and chloroquine as companions to primaquine in a curative drug regimen. Am J Trop Med Hyg 30: 20– 25.
-
11.
Sarma PSA, 1988. Tinidazole: a new drug in the treatment of vivax malaria. Current Therapeutic Res 43: 954– 956.
-
12.
Kim KA, Park JY, Lee JS, Lim S, 2003. Cytochrome P450 2C8 and CYP3A4/5 are involved in chloroquine metabolism in human liver microsomes. Arch Pharm Res 26: 631– 637.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 346 | 323 | 16 |
| Full Text Views | 357 | 7 | 0 |
| PDF Downloads | 82 | 7 | 0 |