Reversal of Chloroquine Resistance of Plasmodium vivax in Aotus Monkeys

Antimicrob Agents Chemother. 2018 Aug 27;62(9):e00582-18. doi: 10.1128/AAC.00582-18. Print 2018 Sep.

Abstract

Chloroquine-resistant (CQR) vivax malaria has emerged as a threat to the malaria elimination agenda. The objective of this study was to assess if a combination of chloroquine (CQ) and prochlorperazine was able to reverse CQ resistance of the Plasmodium vivax AMRU-1 strain from Papua New Guinea in infected Aotus monkeys. For this purpose, in two independent experimental drug efficacy trials, a total of 18 Aotus monkeys infected with blood obtained from donor animals were randomly assigned to treatment and control groups and orally administered CQ at 10 mg/kg or prochlorperazine at 20 mg/kg, alone or in combination, for five consecutive days. Reversal of CQR was achieved in animals that received the drug combination, whereas neither drug alone produced cures. This same drug combination reverses CQR in P. falciparum and could be an alternative for treatment in humans with chloroquine-resistant P. vivax infections.

Keywords: Aotus monkeys; Plasmodium vivax; animal models; chloroquine resistance; resistance reversals.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antimalarials / pharmacology*
  • Chloroquine / pharmacology*
  • Drug Resistance / drug effects
  • Female
  • Haplorhini / microbiology*
  • Malaria, Falciparum / drug therapy
  • Malaria, Vivax / drug therapy*
  • Malaria, Vivax / microbiology
  • Male
  • Papua New Guinea
  • Plasmodium falciparum / drug effects
  • Plasmodium vivax / drug effects*

Substances

  • Antimalarials
  • Chloroquine