title: Sulfadoxine-pyrimethamine resistance in Plasmodium falciparum: a zoomed image at the molecular level within a geographic context.
abstract: Antimalarial chemotherapy is one of the main pillars in the prevention and control of malaria. Following widespread resistance of Plasmodium falciparum to chloroquine, sulfadoxine-pyrimethamine came to the scene as an alternative to the cheap and well-tolerated chloroquine. However, widespread resistance to sulfadoxine-pyrimethamine has been documented. In vivo efficacy tests are the gold standard for assessing drug resistance and treatment failure. However, they have many disadvantages, such as influence of host immunity and drug pharmacokinetics. In vitro tests of antimalarial drug efficacy also have many technical difficulties. Molecular markers of resistance have emerged as epidemiologic tools to investigate antimalarial drug resistance even before becoming clinically evident. Mutations in P. falciparum dihydrofolate reductase and dihydrofolate synthase have been extensively studied as molecular markers for resistance to pyrimethamine and sulfadoxine, respectively. This review highlights the resistance of P. falciparum at the molecular level presenting both supporting and opposing studies on the utility of molecular markers.
authors.affiliation: Department of Parasitology, Medical Research Institute, Alexandria University, Alexandria, Egypt. rashadqb@yahoo.com
authors.forename: Rashad
authors.initials: R
authors.lastname: Abdul-Ghani
authors.forename: Hoda F
authors.initials: HF
authors.lastname: Farag
authors.forename: Amal F
authors.initials: AF
authors.lastname: Allam
mesh_terms: D000962:Antimalarials / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D002986:Clinical Trials as Topic; D004094:Dihydropteroate Synthase / Q000235:genetics / Q000378:metabolism; D004338:Drug Combinations; D004351:Drug Resistance; D019143:Evolution, Molecular; D017125:Genes, Protozoan; D005843:Geography; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity; D017354:Point Mutation; D011739:Pyrimethamine / Q000494:pharmacology*; D013413:Sulfadoxine / Q000494:pharmacology*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics / Q000378:metabolism
chemical_list: D000962:Antimalarials; D015415:Biomarkers; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; D011739:Pyrimethamine