Strategies to reverse drug resistance in malaria

Curr Opin Infect Dis. 2007 Dec;20(6):598-604. doi: 10.1097/QCO.0b013e3282f1673a.


Purpose of review: Despite the current success of artemisinin combination therapy, the threat of drug-resistant falciparum malaria remains severe. Reversal of resistance to old drugs remains one strategy to deal with this problem. This review highlights recent significant findings.

Recent findings: This review provides a brief description of current antimalarials, their known or putative targets and mechanisms of resistance (where applicable). The main focus is recent reports on chloroquine resistance-reversing agents, including primaquine, so-called 'reversed chloroquines', novel resistance reversers such as xanthenes and two new mefloquine resistance-reversing compounds. A number of patents also report interesting new chloroquine resistance reversers, most notably HIV protease inhibitors. The review is confined to Plasmodium falciparum.

Summary: Only chlorpheniramine has so far shown some clinical utility as a chloroquine resistance reverser. Recent observations, however, that both primaquine and HIV protease inhibitors are chloroquine resistance reversers may eventually prove to be of clinical significance. 'Reversed chloroquines' are a scientifically innovative new class of antimalarial that both kill malaria parasites and have the potential to reverse resistance to their own antimalarial pharmacophore.

Publication types

  • Review

MeSH terms

  • Animals
  • Antimalarials / administration & dosage
  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • Drug Resistance*
  • Humans
  • Malaria, Falciparum / drug therapy
  • Malaria, Falciparum / parasitology*
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / genetics


  • Antimalarials