title: Defining the origin of Plasmodium falciparum resistant dhfr isolates in Senegal.
abstract: We previously reported a high baseline prevalence of mutations in the dhfr and dhps genes of Plasmodium falciparum throughout Senegal. The highest prevalence of the triple dhfr pyrimethamine associated mutations were found in isolates obtained in the western part of the country near the capital city of Dakar. In this study, we sought out to determine the relatedness of dhfr wild type and mutated strains by analyzing three microsatellite regions upstream of the dhfr locus. Twenty-six of the 31 wild type strains had a unique microsatellite pattern. In contrast, of the 17 isolates containing the triple mutation in dhfr, 11 had an identical microsatellite pattern. Diverse geographical isolates in Senegal containing the triple dhfr mutation have arisen from a limited number of ancestral strains. In addition, we demonstrate that these isolates have shared ancestry with the previously reported triple mutation haplotype found in Tanzania, South Africa, and southeast Asia. This common ancestry may have implications for the malaria control strategy for reducing the spread of sulfadoxine-pyrimethamine resistance in Senegal and elsewhere in Africa.
authors.affiliation: Department of Parasitology and Mycology, Dantec Hospital, Cheikh Anta Diop University, Dakar, Senegal.
authors.forename: D
authors.initials: D
authors.lastname: Ndiaye
authors.forename: J P
authors.initials: JP
authors.lastname: Daily
authors.forename: O
authors.initials: O
authors.lastname: Sarr
authors.forename: O
authors.initials: O
authors.lastname: Ndir
authors.forename: O
authors.initials: O
authors.lastname: Gaye
authors.forename: S
authors.initials: S
authors.lastname: Mboup
authors.forename: C
authors.initials: C
authors.lastname: Roper
authors.forename: D F
authors.initials: DF
authors.lastname: Wirth
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D019075:Electrophoresis, Capillary; D019143:Evolution, Molecular; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology*; D018895:Microsatellite Repeats / Q000235:genetics; D010963:Plasmodium falciparum / Q000201:enzymology / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012675:Senegal; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry / Q000235:genetics*
chemical_list: D000962:Antimalarials; D016054:DNA, Protozoan; D013762:Tetrahydrofolate Dehydrogenase