Causal prophylactic efficacy of primaquine, tafenoquine, and atovaquone-proguanil against Plasmodium cynomolgi in a rhesus monkey model.
Since the 1940s, the large animal model to assess novel causal prophylactic antimalarial agents has been the Plasmodium cynomolgi sporozoite-infected Indian-origin rhesus monkey. In 2009 the model was reassessed with 3 clinical standards: primaquine (PQ), tafenoquine (TQ), and atovaquone-proguanil. Both control monkeys were parasitemic on day 8 post-sporozoite inoculation on day 0. Primaquine at 1.78 mg base/kg/day on days (-1) to 8 protected 1 monkey and delayed parasitemia patency of the other monkey to day 49. Tafenoquine at 6 mg base/kg/day on days (-1) to 1 protected both monkeys. However, atovaquone-proguanil at 10 mg atovaquone/kg/day on days (-1) to 8 did not protect either monkey and delayed patency only to days 18-19. Primaquine and TQ at the employed regimens are proposed as appropriate doses of positive control drugs for the model at present.
Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910; * Department of Veterinary Medicine, United States Army Medical Component-Armed Forces Research Institute of Medical Sciences (USAMC-AFRIMS), Bangkok, Thailand 10400. Correspondence should be sent to: charles.a.ditusa.mil@mail.mil.
Charles
C
DiTusa
Michael P
MP
Kozar
Brandon
B
Pybus
Jason
J
Sousa
Jonathan
J
Berman
Montip
M
Gettayacamin
Rawiwan
R
Im-erbsin
Anchalee
A
Tungtaeng
Colin
C
Ohrt
D000634:Aminoquinolines / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000962:Antimalarials / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D053626:Atovaquone / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004338:Drug Combinations; D008253:Macaca mulatta; D008288:Malaria / Q000188:drug therapy / Q000517:prevention & control*; D018512:Parasitemia / Q000188:drug therapy / Q000517:prevention & control; D016789:Plasmodium cynomolgi / Q000187:drug effects*; D011319:Primaquine / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D002727:Proguanil / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use
D000634:Aminoquinolines; D000962:Antimalarials; D004338:Drug Combinations; C109496:atovaquone, proguanil drug combination; C055852:tafenoquine; D011319:Primaquine; D002727:Proguanil; D053626:Atovaquone