title: Limited polymorphisms in k13 gene in Plasmodium falciparum isolates from Dakar, Senegal in 2012-2013.
abstract: BACKGROUND
  The emergence of Plasmodium falciparum resistance to artemisinin and its derivatives, manifested as delayed parasite clearance following the treatment, has developed in Southeast Asia. The spread of resistance to artemisinin from Asia to Africa may be catastrophic for malaria control and elimination worldwide. Recently, mutations in the propeller domain of the Kelch 13 (k13) gene (PF3D71343700) were associated with in vitro resistance to artemisinin and with delayed clearance after artemisinin treatment in southern Asia. The aim of the study was to characterize the genetic variability of k13 and to evaluate the molecular resistance to artemisinin for the first time in Senegal.
  
  
  METHODS
  Plasmodium falciparum isolates were collected from 138 malaria patients in Dakar and its districts during the rainy season of October 2012 to January 2013 at the Hôpital Principal de Dakar. The k13 gene was amplified using nested PCR and sequenced.
  
  
  RESULTS
  A very limited variability within the k13 gene in Senegalese P. falciparum isolates was identified. No polymorphism was detected in the six k13-propeller blades. Only two mutations, T149S (6.3%) and K189T (42.2%), and one (N) or two (NN) asparagine insertion at the codon 142 (4.7 and 6.3%, respectively) were detected in the Plasmodium/Apicomplexa-specific domain. None of the polymorphisms associated with artemisinin resistance in Southeast Asia was detected in the 138 P. falciparum from Dakar.
  
  
  CONCLUSIONS
  The present data do not suggest widespread artemisinin resistance in Dakar in 2012-2013. Notably, the C580Y, R539T or Y493H substitutions that were associated with in vitro resistance or delayed parasite clearance in Southeast Asia were not observed in Dakar, nor were any of the polymorphisms observed in parasites from Southeast Asia, nor the M476I mutation that was selected in vitro with artemisinin pressure in a African parasite line.
authors.forename: Marylin
authors.initials: M
authors.lastname: Torrentino-Madamet
authors.forename: Bécaye
authors.initials: B
authors.lastname: Fall
authors.forename: Nicolas
authors.initials: N
authors.lastname: Benoit
authors.forename: Cheikhou
authors.initials: C
authors.lastname: Camara
authors.forename: Rémy
authors.initials: R
authors.lastname: Amalvict
authors.forename: Mansour
authors.initials: M
authors.lastname: Fall
authors.forename: Pierre
authors.initials: P
authors.lastname: Dionne
authors.forename: Kadidiatou
authors.initials: K
authors.lastname: Ba Fall
authors.forename: Aminata
authors.initials: A
authors.lastname: Nakoulima
authors.forename: Bakary
authors.initials: B
authors.lastname: Diatta
authors.forename: Yaya
authors.initials: Y
authors.lastname: Diemé
authors.forename: Didier
authors.initials: D
authors.lastname: Ménard
authors.forename: Boubacar
authors.initials: B
authors.lastname: Wade
authors.affiliation: Aix Marseille Université, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Marseille, France. bruno.pradines@free.fr.
authors.forename: Bruno
authors.initials: B
authors.lastname: Pradines
mesh_terms: D019943:Amino Acid Substitution; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D004351:Drug Resistance; D005838:Genotype; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D016778:Malaria, Falciparum / Q000469:parasitology; D020125:Mutation, Missense; D010963:Plasmodium falciparum / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics*; D012675:Senegal; D017422:Sequence Analysis, DNA
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D016054:DNA, Protozoan; D007783:Lactones; D015800:Protozoan Proteins; C075875:artemisin