Drug Resistance Updates
Volume 1, Issue 6 , Pages 389-396, 1998

P. falciparum dihydrofolate reductase and dihydropteroate synthase mutations: epidemiology and role in clinical resistance to antifolates

  • Christopher V. Plowe

      Affiliations

    • Molecular Parasitology and Malaria Field Studies Unit, Center for Vaccine Development/Division of Geographic Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
    • Corresponding Author InformationCorrespondence to: Christopher V. Plowe MD, MPH, Molecular Parasitology and Malaria Field Studies Unit, Center for Vaccine Development/Division of Geographic Medicine, University of Maryland School of Medicine, 685 West Baltimore Street, HSF 480, Baltimore, Maryland 21201 USA, Tel: 410-706-5328; Fax: 410-706-6205
    • ,
  • James G. Kublin

      Affiliations

    • Molecular Parasitology and Malaria Field Studies Unit, Center for Vaccine Development/Division of Geographic Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
    • ,
  • Ogobara K. Doumbo

      Affiliations

    • Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy and Odonto-stomatology, University of Mali, Bamako, Mali

Received 16 July 1998; received in revised form 19 October 1998; accepted 20 October 1998.

Abstract 

Plasmodium falciparum resistance to the antifolates has arisen rapidly in Asia and South America, and threatens the usefulness of these drugs in Africa. In vitro resistance to the antifolates is determined by mutations in parasite dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS). The role of DHFR and DHPS mutations in therapeutic failure of antifolate antimalarials is less clear. This review summarizes molecular epidemiological surveys, studies of in vivo selection of mutant alleles by drug treatment, and prospective studies of the ability of mutation-specific assays to predict clinical outcomes, and discusses the potential use of these assays for surveillance of resistance.

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PII: S1368-7646(98)80014-9

Drug Resistance Updates
Volume 1, Issue 6 , Pages 389-396, 1998

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