title: Molecular markers of antifolate resistance in Plasmodium falciparum isolates from Luanda, Angola.
abstract: BACKGROUND
  Plasmodium falciparum malaria remains a leading health problem in Africa and its control is seriously challenged by drug resistance. Although resistance to the sulphadoxine-pyrimethamine (SP) is widespread, this combination remains an important component of malaria control programmes as intermittent preventive therapy (IPT) for pregnant women and children. In Angola, resistance patterns have been poorly characterized, and IPT has been employed for pregnant women since 2006. The aim of this study was to assess the prevalence of key antifolate resistance mediating polymorphisms in the pfdhfr and pfdhps genes in P. falciparum samples from Angola.
  
  
  METHODS
  Plasmodium falciparum samples collected in Luanda, in 2007, were genotyped by amplification and DNA forward and reverse sequencing of the pfdhfr and pfdhps genes.
  
  
  RESULTS
  The most prevalent polymorphisms identified were pfdhfr 108N (100%), 51I (93%), 59R (57%) and pfdhps 437G (93%). Resistance-mediating polymorphisms in pfdhps less commonly observed in West Africa were also identified (540E in 10%, 581G in 7% of samples).
  
  
  CONCLUSIONS
  This study documents an important prevalence of 4 P. falciparum polymorphisms that predicts an antifolate resistance in Luanda. Further, some samples presented additional mutations associated to high-level resistance. These results suggest that the use of SP for IPT may no longer be warranted in Angola.
authors.affiliation: Laboratory of Malaria Research, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil.
authors.forename: Bianca E
authors.initials: BE
authors.lastname: Gama
authors.forename: Guilhermina A L
authors.initials: GA
authors.lastname: Pereira-Carvalho
authors.forename: Florbela J I
authors.initials: FJ
authors.lastname: Lutucuta Kosi
authors.forename: Natália K
authors.initials: NK
authors.lastname: Almeida de Oliveira
authors.forename: Filomeno
authors.initials: F
authors.lastname: Fortes
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
authors.forename: Virgílio E
authors.initials: VE
authors.lastname: do Rosário
authors.forename: Cláudio Tadeu
authors.initials: CT
authors.lastname: Daniel-Ribeiro
authors.forename: Maria
authors.initials: M
authors.lastname: de Fátima Ferreira-da-Cruz
mesh_terms: D000328:Adult; D000810:Angola; D000962:Antimalarials / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D004094:Dihydropteroate Synthase / Q000235:genetics; D004351:Drug Resistance; D005260:Female; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D005787:Gene Frequency; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D011110:Polymorphism, Genetic; D011247:Pregnancy; D015800:Protozoan Proteins / Q000235:genetics; D017422:Sequence Analysis, DNA; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics
chemical_list: D000962:Antimalarials; D005493:Folic Acid Antagonists; D005819:Genetic Markers; D015800:Protozoan Proteins; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase