title: Prevalence of pfmdr1 alleles associated with artemether-lumefantrine tolerance/resistance in Maputo before and after the implementation of artemisinin-based combination therapy.
abstract: BACKGROUND
  Mozambique implemented artemisinin-based combinations therapy (ACT) using artemether-lumefantrine (AL) as the first-line treatment for uncomplicated malaria in 2009. AL remains highly efficacious, but widespread use may soon facilitate emergence of artemisinin tolerance/resistance. The prevalence of pfmdr1 different alleles in Maputo and Mozambique is not known, either after or before the introduction of ACT. Pfmdr1 molecular markers related to Plasmodium falciparum susceptibility were analysed before and after transition to ACT.
  
  
  METHODS
  A first group of samples was collected between June 2003 and June 2005 and a second group in the period between March 2010 and March 2012. Three alleles were analysed by PCR-RFLP: N86Y, Y184F and D1246Y, in the pfmdr1 gene.
  
  
  RESULTS
  Alleles N86, 184F and D1246 increased from 19.5, 19.6 and 74.4% in 2003-2005 to 73.2, 22.7 and 96.7% in 2010-2012, respectively. After implementation of ACT (2010-2012), pfmdr1 haplotypes, either two- and three-codon basis, were generally less diverse than before the implementation of ACT (2003-2005). The prevalence of haplotypes N86-184Y, N86-D1246 and 184Y-D1246 increased from 12,2, 27.3 and 71.7% in 2003-2005 to 59.4, 84.3 and 78.6% in 2010-2012. The three-codon basis haplotypes NFD and NYD also increased significantly during the same period.
  
  
  CONCLUSIONS
  The alleles N86 and 184 F and the triple haplotype N86-184 F-D1246 showed a significantly increased prevalence after introduction of ACT.
authors.affiliation: Faculdade de Medicina, Departamento de CiênciasFisiológicas, Universidade Eduardo Mondlane, Av Salvador Allende 702, Maputo, Moçambique. loboelsa@yahoo.com.br.
authors.forename: Elsa
authors.initials: E
authors.lastname: Lobo
authors.forename: Bruno
authors.initials: B
authors.lastname: de Sousa
authors.forename: Soraia
authors.initials: S
authors.lastname: Rosa
authors.forename: Paula
authors.initials: P
authors.lastname: Figueiredo
authors.forename: Lis
authors.initials: L
authors.lastname: Lobo
authors.forename: Sara
authors.initials: S
authors.lastname: Pateira
authors.forename: Natercia
authors.initials: N
authors.lastname: Fernandes
authors.forename: Fatima
authors.initials: F
authors.lastname: Nogueira
mesh_terms: D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000494:pharmacology*; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics*; D004983:Ethanolamines / Q000494:pharmacology*; D005449:Fluorenes / Q000494:pharmacology*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000469:parasitology*; D009073:Mozambique / Q000453:epidemiology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence
chemical_list: D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C513498:Mdr1 protein, Plasmodium falciparum
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