title: Molecular surveillance of mutations in dihydrofolate reductase and dihydropteroate synthase genes of Plasmodium falciparum in Ethiopia.
abstract: Point mutations in the genes for dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) of Plasmodium falciparum isolates are associated with sulfadoxine/pyrimethamine (SP) treatment failure, respectively. This study was conducted to assess the prevalence of SP resistance in P. falciparum isolates collected at the Jimma Health Center in southwestern Ethiopia. In this study, the genetic profile of P. falciparum isolates with respect to DHFR and DHPS genes was assessed in 124 individuals. The prevalence of single, double, and multiple mutations in these genes was calculated. The sequence profile showed that all samples carried a double mutation at the positions 51 and 108 (I51N108) in the DHFR gene. Sixty-seven (54.03%) of the isolates had an additional third mutation at position 59, resulting in the triple mutant I51R59N108. All isolates carried mutations G437 and E540 in the DHPS gene. Two isolates (1.61%) had additional mutations at codon 581 (A581).
authors.affiliation: Faculty of Medicine, Department of Microbiology, Immunology and Parasitology, Addis Ababa University Addis Ababa, Ethiopia. tamiratgw2002@yahoo.com
authors.forename: Tamirat
authors.initials: T
authors.lastname: Gebru-Woldearegai
authors.forename: Asrat
authors.initials: A
authors.lastname: Hailu
authors.forename: Martin P
authors.initials: MP
authors.lastname: Grobusch
authors.forename: Jürgen F J
authors.initials: JF
authors.lastname: Kun
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D017931:DNA Primers; D016054:DNA, Protozoan / Q000032:analysis; D004094:Dihydropteroate Synthase / Q000235:genetics; D004338:Drug Combinations; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005002:Ethiopia / Q000453:epidemiology; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D015995:Prevalence; D011739:Pyrimethamine / Q000494:pharmacology* / Q000627:therapeutic use; D013413:Sulfadoxine / Q000494:pharmacology* / Q000627:therapeutic use; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics
chemical_list: D000962:Antimalarials; D017931:DNA Primers; D016054:DNA, Protozoan; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; D011739:Pyrimethamine