title: Surveillance of molecular markers of Plasmodium falciparum resistance to sulphadoxine-pyrimethamine 5 years after the change of malaria treatment policy in Ghana.
abstract: In 2005, sulphadoxine-pyrimethamine (SP) became the drug of choice for intermittent preventive treatment of Plasmodium falciparum malaria in pregnancy (IPTp) in Ghana. Reports suggest the use of SP by others to treat uncomplicated malaria. Because of the increased use of SP, the prevalence of mutations in the genes, dihydrofolate reductase (dhfr), and dihydropteroate synthetase (dhps), linked to SP resistance in P. falciparum were determined. Blood samples from 945 children with uncomplicated malaria collected at nine sites from 2003 to 2010 were analyzed using polymerase chain reaction and restriction fragment length polymorphism. Prevalence of the dhfr triple and dhfr plus dhps quadruple mutations showed significant increase in trend from 2003 to 2010 (χ(2) = 18.78, P < 0.001, χ(2) = 15.11, P < 0.001, respectively). For dhps double mutant G437 + E540 the prevalence was low (1.12%) caused by the very low prevalence of E540. Our findings show the wide use of SP in Ghana and therefore its use for IPTp needs to be closely monitored.
authors.affiliation: Noguchi Memorial Institute for Medical Research, Legon, Accra, Ghana. nduah@noguchi.mimcom.org
authors.forename: Nancy O
authors.initials: NO
authors.lastname: Duah
authors.forename: Neils B
authors.initials: NB
authors.lastname: Quashie
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Abuaku
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sebeny
authors.forename: Karl C
authors.initials: KC
authors.lastname: Kronmann
authors.forename: Kwadwo A
authors.initials: KA
authors.lastname: Koram
mesh_terms: D000429:Alcohol Oxidoreductases; D000483:Alleles; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers; D004094:Dihydropteroate Synthase / Q000235:genetics / Q000378:metabolism; D004338:Drug Combinations; D004351:Drug Resistance; D015971:Gene Expression Regulation, Enzymologic; D005869:Ghana / Q000453:epidemiology; D006291:Health Policy; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000453:epidemiology / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011159:Population Surveillance; D011739:Pyrimethamine / Q000494:pharmacology* / Q000627:therapeutic use; D013413:Sulfadoxine / Q000494:pharmacology* / Q000627:therapeutic use; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D000962:Antimalarials; D015415:Biomarkers; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D000429:Alcohol Oxidoreductases; C021496:lactate-malate transhydrogenase; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; D011739:Pyrimethamine