Killing the hypnozoite--drug discovery approaches to prevent relapse in Plasmodium vivax

Pathog Glob Health. 2015 May;109(3):107-22. doi: 10.1179/2047773215Y.0000000013. Epub 2015 Apr 18.

Abstract

The eradication of malaria will only be possible if effective, well-tolerated medicines kill hypnozoites in vivax and ovale malaria, and thus prevent relapses in patients. Despite progress in the 8-aminoquinoline series, with tafenoquine in Phase III showing clear benefits over primaquine, the drug discovery challenge to identify hypnozoiticidal or hypnozoite-activating compounds has been hampered by the dearth of biological tools and assays, which in turn has been limited by the immense scientific and logistical challenges associated with accessing relevant human tissue and sporozoites. This review summarises the existing drug discovery series and approaches concerning the goal to block relapse.

Keywords: Drug discovery assays; Hypnozoite,; Plasmodium vivax,; Radical cure,; Strategy,.

Publication types

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

MeSH terms

  • Aminoquinolines / pharmacology
  • Antimalarials / pharmacology
  • Chemical and Drug Induced Liver Injury / prevention & control
  • Disease Eradication / trends*
  • Drug Discovery / trends*
  • Humans
  • Liver / drug effects*
  • Liver / parasitology
  • Liver / pathology
  • Malaria, Vivax / drug therapy*
  • Malaria, Vivax / prevention & control
  • Plasmodium vivax / drug effects*
  • Plasmodium vivax / isolation & purification
  • Recurrence
  • Sporozoites / drug effects*

Substances

  • Aminoquinolines
  • Antimalarials
  • tafenoquine
  • 8-aminoquinoline