Causal prophylactic efficacy of primaquine, tafenoquine, and atovaquone-proguanil against Plasmodium cynomolgi in a rhesus monkey model

J Parasitol. 2014 Oct;100(5):671-3. doi: 10.1645/13-480.1. Epub 2014 Apr 29.

Abstract

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.

MeSH terms

  • Aminoquinolines / pharmacokinetics
  • Aminoquinolines / pharmacology*
  • Aminoquinolines / therapeutic use
  • Animals
  • Antimalarials / pharmacokinetics
  • Antimalarials / pharmacology*
  • Antimalarials / therapeutic use
  • Atovaquone / pharmacokinetics
  • Atovaquone / pharmacology*
  • Atovaquone / therapeutic use
  • Disease Models, Animal
  • Drug Combinations
  • Macaca mulatta
  • Malaria / drug therapy
  • Malaria / prevention & control*
  • Parasitemia / drug therapy
  • Parasitemia / prevention & control
  • Plasmodium cynomolgi / drug effects*
  • Primaquine / pharmacokinetics
  • Primaquine / pharmacology*
  • Primaquine / therapeutic use
  • Proguanil / pharmacokinetics
  • Proguanil / pharmacology*
  • Proguanil / therapeutic use

Substances

  • Aminoquinolines
  • Antimalarials
  • Drug Combinations
  • atovaquone, proguanil drug combination
  • tafenoquine
  • Primaquine
  • Proguanil
  • Atovaquone