title: Prevalence of single nucleotide polymorphisms in the Plasmodium falciparum multidrug resistance gene (Pfmdr-1) in Korogwe District in Tanzania before and after introduction of artemisinin-based combination therapy.
abstract: Tanzania implemented artemether-lumefantrine (AL) as the first-line treatment for uncomplicated malaria in November of 2006 because of resistance to sulfadoxine-pyrimethamine. AL remains highly efficacious, but widespread use may soon facilitate emergence of artemisinin tolerance/resistance, which initially may be detected at the molecular level as temporal changes in the frequency of single nucleotide polymorphisms (SNPs) in the Pfmdr-1 gene associated with AL resistance. In Tanzania, 830 Plasmodium falciparum-positive samples collected between 2003 and 2010 were examined for SNPs of Pfmdr-1 at codons 86, 184, and 1246. Both the N86 and 184F increased from 2006 to 2010 (logistic regression; N86: odds ratio [95% confidence interval] = 1.35 [1.07-1.71], P = 0.01; 184F: odds ratio = 1.42 [1.07-1.88], P = 0.02), and no change was found for D1246 (odds ratio = 1.01 [0.80-1.28], P = 0.9). The observed changes may be because of introduction of AL, and if so, this finding gives cause for concern and argues for continued surveillance of these molecular markers.
authors.affiliation: Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark. thyge666@gmail.com
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Thomsen
authors.forename: Deus S
authors.initials: DS
authors.lastname: Ishengoma
authors.forename: Bruno P
authors.initials: BP
authors.lastname: Mmbando
authors.forename: John P
authors.initials: JP
authors.lastname: Lusingu
authors.forename: Lasse S
authors.initials: LS
authors.lastname: Vestergaard
authors.forename: Thor G
authors.initials: TG
authors.lastname: Theander
authors.forename: Martha M
authors.initials: MM
authors.lastname: Lemnge
authors.forename: Ib C
authors.initials: IC
authors.lastname: Bygbjerg
authors.forename: Michael
authors.initials: M
authors.lastname: Alifrangis
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000187:drug effects / Q000235:genetics*; D000962:Antimalarials / Q000008:administration & dosage / Q000627:therapeutic use*; D037621:Artemisinins / Q000008:administration & dosage / Q000627:therapeutic use*; D003062:Codon / Q000235:genetics; D003430:Cross-Sectional Studies; D018432:Drug Resistance, Multiple / Q000187:drug effects / Q000235:genetics; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000008:administration & dosage / Q000627:therapeutic use; D005449:Fluorenes / Q000008:administration & dosage / Q000627:therapeutic use; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D000078102:Lumefantrine; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D015800:Protozoan Proteins / Q000187:drug effects / Q000235:genetics*; D013636:Tanzania / Q000453:epidemiology
chemical_list: D018528:ATP-Binding Cassette Transporters; D000962:Antimalarials; D037621:Artemisinins; D003062:Codon; D004983:Ethanolamines; D005449:Fluorenes; D015800:Protozoan Proteins; C059987:mdr gene protein, Plasmodium; C031327:artemisinin; D000078102:Lumefantrine