title: Pyrimethamine-sulfadoxine resistance in Plasmodium falciparum: what next?
abstract: Chemotherapy remains the only practicable tool to control falciparum malaria in sub-Saharan Africa, where >90% of the world's burden of malaria mortality and morbidity occurs. Resistance is rapidly eroding the efficacy of chloroquine, and the combination pyrimethamine-sulfadoxine is the most commonly chosen alternative. Resistant populations of Plasmodium falciparum were selected extremely rapidly in Southeast Asia and South America. If this happens in sub-Saharan Africa, it will be a public health disaster because no inexpensive alternative is currently available. This article reviews the molecular mechanisms of this resistance and discusses how to extend the therapeutic life of antifolate drugs.
authors.affiliation: Department of Genetics, Box 357360, University of Washington, Seattle, WA 98195-7360, USA. sibley@genetics.washington.edu
authors.forename: C H
authors.initials: CH
authors.lastname: Sibley
authors.forename: J E
authors.initials: JE
authors.lastname: Hyde
authors.forename: P F
authors.initials: PF
authors.lastname: Sims
authors.forename: C V
authors.initials: CV
authors.lastname: Plowe
authors.forename: J G
authors.initials: JG
authors.lastname: Kublin
authors.forename: E K
authors.initials: EK
authors.lastname: Mberu
authors.forename: A F
authors.initials: AF
authors.lastname: Cowman
authors.forename: P A
authors.initials: PA
authors.lastname: Winstanley
authors.forename: W M
authors.initials: WM
authors.lastname: Watkins
authors.forename: A M
authors.initials: AM
authors.lastname: Nzila
mesh_terms: D017954:Africa South of the Sahara; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D002738:Chloroquine / Q000494:pharmacology; D004338:Drug Combinations; D004351:Drug Resistance; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008826:Microbial Sensitivity Tests; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D011739:Pyrimethamine / Q000494:pharmacology* / Q000627:therapeutic use; D013413:Sulfadoxine / Q000494:pharmacology* / Q000627:therapeutic use; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002738:Chloroquine; D013762:Tetrahydrofolate Dehydrogenase; D011739:Pyrimethamine