Use of a rhesus Plasmodium cynomolgi model to screen for anti-hypnozoite activity of pharmaceutical substances.
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.
Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. gregory.deye@gmail.com
Gregory A
GA
Deye
Montip
M
Gettayacamin
Pranee
P
Hansukjariya
Rawiwan
R
Im-erbsin
Jetsumon
J
Sattabongkot
Yarrow
Y
Rothstein
Louis
L
Macareo
Susan
S
Fracisco
Kent
K
Bennett
Alan J
AJ
Magill
Colin
C
Ohrt
D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D002738:Chloroquine / Q000627:therapeutic use; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D008253:Macaca mulatta / Q000469:parasitology*; D016780:Malaria, Vivax / Q000188:drug therapy* / Q000517:prevention & control; D018512:Parasitemia / Q000517:prevention & control; D016789:Plasmodium cynomolgi / Q000187:drug effects* / Q000472:pathogenicity*; D010966:Plasmodium vivax / Q000254:growth & development / Q000472:pathogenicity; D011319:Primaquine / Q000627:therapeutic use; D011718:Pyrazinamide / Q000627:therapeutic use; D055502:Secondary Prevention; D034101:Sporozoites / Q000187:drug effects; D014011:Tinidazole / Q000627:therapeutic use; D014223:Triamterene / Q000627:therapeutic use
D000962:Antimalarials; D014011:Tinidazole; D011718:Pyrazinamide; D002738:Chloroquine; D011319:Primaquine; D014223:Triamterene