title: Prevalence of anti-malarial resistance genes in Dakar, Senegal from 2013 to 2014.
abstract: To determine the impact of the introduction of artemisinin-based combination therapy (ACT) on parasite susceptibility, a molecular surveillance for antimalarial drug resistance was conducted on local isolates from the Hôpital Principal de Dakar between November 2013 and January 2014 and between August 2014 and December 2014.
  
  
  
  The prevalence of genetic polymorphisms in antimalarial resistance genes (pfcrt, pfmdr1, pfdhfr and pfdhps) was evaluated in 103 isolates.
  
  
  
  The chloroquine-resistant haplotypes CVIET and CVMET were identified in 31.4 and 3.9 % of the isolates, respectively. The frequency of the pfcrt K76T mutation was increased from 29.3 % in 2013-2014 to 43.2 % in 2014. The pfmdr1 N86Y and Y184F mutations were identified in 6.1 and 53.5 % of the isolates, respectively. The pfdhfr triple mutant (S108N, N51I and C59R) was detected in the majority of the isolates (82.3 %). The prevalence of quadruple mutants (pfdhfr S108N, N51I, C59R and pfdhps A437G) was 40.4 %. One isolate (1.1 %) harboured the pfdhps mutations A437G and K540E and the pfdhfr mutations S108N, N51I and C59R.
  
  
  
  Despite a decline in the prevalence of chloroquine resistance due to the official withdrawal of the drug and to the introduction of ACT, the spread of resistance to chloroquine has continued. Furthermore, susceptibility to amodiaquine may be decreased as a result of cross-resistance. The frequency of the pfmdr1 mutation N86Y declined while the Y184F mutation increased in prevalence, suggesting that selective pressure is acting on pfmdr1, leading to a high prevalence of mutations in these isolates and the lack of specific mutations. The 50.5 % prevalence of the pfmdr1 polymorphisms N86Y and Y184F suggests a decrease in lumefantrine susceptibility. Based on these results, intensive surveillance of ACT partner drugs must be conducted regularly in Senegal.
authors.affiliation: Unité de Parasitologie et d'Entomologie, Département des Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, Brétigny Sur Orge, France.
authors.forename: Agathe
authors.initials: A
authors.lastname: Boussaroque
authors.affiliation: Laboratoire d'étude de la chimiosensibilité du paludisme, Fédération des Laboratoires, Hôpital Principal de Dakar, Dakar, Senegal.
authors.forename: Bécaye
authors.initials: B
authors.lastname: Fall
authors.affiliation: Equipe Résidente de Recherche en Infectiologie Tropicale, Institut de Recherche Biomédicale des Armées, Hôpital d'Instruction des Armées, Marseille, France.|Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, Marseille, France.|Centre National de Référence du Paludisme, Marseille, France.
authors.forename: Marylin
authors.initials: M
authors.lastname: Madamet
authors.affiliation: Service des Urgences, Hôpital Principal de Dakar, Dakar, Senegal.
authors.forename: Khalifa Ababacar
authors.initials: KA
authors.lastname: Wade
authors.affiliation: Service de Réanimation Médicale, Hôpital Principal de Dakar, Dakar, Senegal.
authors.forename: Mansour
authors.initials: M
authors.lastname: Fall
authors.affiliation: Service de Pédiatrie, Hôpital Principal de Dakar, Dakar, Senegal.
authors.forename: Aminata
authors.initials: A
authors.lastname: Nakoulima
authors.affiliation: Service de Pathologie Infectieuse, Hôpital Principal de Dakar, Dakar, Senegal.
authors.forename: Khadidiatou Ba
authors.initials: KB
authors.lastname: Fall
authors.affiliation: Maternité Hôpital Principal de Dakar, Dakar, Senegal.
authors.forename: Pierre
authors.initials: P
authors.lastname: Dionne
authors.affiliation: Equipe Résidente de Recherche en Infectiologie Tropicale, Institut de Recherche Biomédicale des Armées, Hôpital d'Instruction des Armées, Marseille, France.|Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, Marseille, France.|Centre National de Référence du Paludisme, Marseille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Benoit
authors.affiliation: Service de Réanimation Médicale, Hôpital Principal de Dakar, Dakar, Senegal.|Chefferie, Hôpital Principal de Dakar, Dakar, Senegal.
authors.forename: Bakary
authors.initials: B
authors.lastname: Diatta
authors.affiliation: Laboratoire d'étude de la chimiosensibilité du paludisme, Fédération des Laboratoires, Hôpital Principal de Dakar, Dakar, Senegal.
authors.forename: Yaya
authors.initials: Y
authors.lastname: Diemé
authors.affiliation: Chefferie, Hôpital Principal de Dakar, Dakar, Senegal.
authors.forename: Boubacar
authors.initials: B
authors.lastname: Wade
authors.affiliation: Unité de Parasitologie et d'Entomologie, Département des Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, Brétigny Sur Orge, France. bruno.pradines@free.fr.|Laboratoire d'étude de la chimiosensibilité du paludisme, Fédération des Laboratoires, Hôpital Principal de Dakar, Dakar, Senegal. bruno.pradines@free.fr.|Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, Marseille, France. bruno.pradines@free.fr.|Centre National de Référence du Paludisme, Marseille, France. bruno.pradines@free.fr.
authors.forename: Bruno
authors.initials: B
authors.lastname: Pradines
mesh_terms: D019943:Amino Acid Substitution; D000655:Amodiaquine / Q000494:pharmacology; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance; D017125:Genes, Protozoan; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D010453:Peptide Synthases / Q000235:genetics; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D011110:Polymorphism, Genetic; D015995:Prevalence; D015800:Protozoan Proteins / Q000235:genetics; D012675:Senegal; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics
chemical_list: D000655:Amodiaquine; D000962:Antimalarials; D002738:Chloroquine; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010453:Peptide Synthases; D015800:Protozoan Proteins; D013762:Tetrahydrofolate Dehydrogenase; C513498:Mdr1 protein, Plasmodium falciparum; C416369:PfCRT protein, Plasmodium falciparum; C020041:dihydrofolate synthetase
keywords: Anti-malarial; In vitro; Malaria; Molecular marker; Plasmodium falciparum; Resistance; Senegal