Mechanisms of resistance of malaria parasites to antifolates.


Journal Article (Review)

Antifolate antimalarial drugs interfere with folate metabolism, a pathway essential to malaria parasite survival. This class of drugs includes effective causal prophylactic and therapeutic agents, some of which act synergistically when used in combination. Unfortunately, the antifolates have proven susceptible to resistance in the malaria parasite. Resistance is caused by point mutations in dihydrofolate reductase and dihydropteroate synthase, the two key enzymes in the folate biosynthetic pathway that are targeted by the antifolates. Resistance to these drugs arises relatively rapidly in response to drug pressure and is now common worldwide. Nevertheless, antifolate drugs remain first-line agents in several sub-Saharan African countries where chloroquine resistance is widespread, at least partially because they remain the only affordable, effective alternative. New antifolate combinations that are more effective against resistant parasites are being developed and in one case, recently introduced into use. Combining these antifolates with drugs that act on different targets in the parasite should greatly enhance their effectiveness as well as deter the development of resistance. Molecular epidemiological techniques for monitoring parasite drug resistance may contribute to development of strategies for prolonging the useful therapeutic life of this important class of drugs.

Full Text

Cited Authors

  • Gregson, A; Plowe, CV

Published Date

  • March 2005

Published In

Volume / Issue

  • 57 / 1

Start / End Page

  • 117 - 145

PubMed ID

  • 15734729

Pubmed Central ID

  • 15734729

Electronic International Standard Serial Number (EISSN)

  • 1521-0081

International Standard Serial Number (ISSN)

  • 0031-6997

Digital Object Identifier (DOI)

  • 10.1124/pr.57.1.4


  • eng