title: Characterization of Plasmodium falciparum genes associated with drug resistance in Hodh Elgharbi, a malaria hotspot near Malian-Mauritanian border.
abstract: A malaria hotspot in the southeastern region of Mauritania, near the Malian border, may hamper malaria control strategies. The objectives were to estimate the prevalence of genetic polymorphisms associated with drug resistance in Plasmodium falciparum isolates and establish baseline data.
  
  
  
  The study was conducted in two malaria-endemic areas in Hodh Elgharbi, situated in the Malian-Mauritanian border area. Blood samples were collected from symptomatic patients. Single nucleotide polymorphisms in Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps were genotyped using PCR-restriction fragment length polymorphism, DNA sequencing and primer extension. The Pfmdr1 gene copy number was determined by real-time PCR.
  
  
  
  Of 280 P. falciparum-infected patients, 193 (68.9%) carried the Pfcrt 76T mutant allele. The Pfmdr1 86Y and 184F mutations were found in 61 (23.1%) of 264 isolates and 167 (67.6%) of 247 samples that were successfully genotyped, respectively. Pfmdr1 mutant alleles 1034C, 1042D and 1246Y were rarely observed. Of 102 P. falciparum isolates analysed, ten (9.8%) had more than one copy of Pfmdr1 gene. The prevalence of isolates harbouring at least triple mutant Pfdhfr 51I, 59R, 108 N/T was 42% (112/268), of which 42 (37.5%) had an additional Pfdhps 437G mutation. The Pfdhps 540E mutation was observed in four isolates (1.5%), including three associated with Pfdhfr triple mutant. Only two quintuple mutants (Pfdhfr-51I-59R-108N Pfdhps-437G-540E) were observed.
  
  
  
  The observed mutations in Pfdhfr, Pfdhps, Pfmdr1, and Pfcrt may jeopardize the future of seasonal malaria chemoprevention based on amodiaquine-sulfadoxine-pyrimethamine, intermittent preventive treatment for pregnant women using sulfadoxine-pyrimethamine, and treatment with artesunate-amodiaquine. Complementary studies should be carried out to document the distribution, origin and circulation of P. falciparum populations in this region and more widely in the country to assess the risk of the spread of resistance.
authors.affiliation: Unité de Recherche «Génomes et Milieux», Faculté des Sciences et Techniques, Université de Nouakchott Al-Aasriya, Nouveau campus universitaire, BP 5026, Nouakchott, Mauritania. salem0606@yahoo.fr.
authors.forename: Mohamed Salem
authors.initials: MS
authors.lastname: Ould Ahmedou Salem
authors.affiliation: Unité de Recherche «Génomes et Milieux», Faculté des Sciences et Techniques, Université de Nouakchott Al-Aasriya, Nouveau campus universitaire, BP 5026, Nouakchott, Mauritania.
authors.forename: Khadijetou
authors.initials: K
authors.lastname: Mint Lekweiry
authors.affiliation: Unité Parasitologie et entomologie, Département des maladies infectieuses, Institut de Recherche Biomédicale des Armées, Marseille, France.|Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Aix-Marseille Université, UM 63, CNRS 7278, IRD 198, Inserm 1095, AP-HM, Institut Hospitalo-Universitaire (IHU) - Méditerranée Infection, 19-21 Boulevard Jean Moulin, 13005, Marseille, France.
authors.forename: Houssem
authors.initials: H
authors.lastname: Bouchiba
authors.affiliation: Unité Parasitologie et entomologie, Département des maladies infectieuses, Institut de Recherche Biomédicale des Armées, Marseille, France.|Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Aix-Marseille Université, UM 63, CNRS 7278, IRD 198, Inserm 1095, AP-HM, Institut Hospitalo-Universitaire (IHU) - Méditerranée Infection, 19-21 Boulevard Jean Moulin, 13005, Marseille, France.
authors.forename: Aurelie
authors.initials: A
authors.lastname: Pascual
authors.affiliation: Unité Parasitologie et entomologie, Département des maladies infectieuses, Institut de Recherche Biomédicale des Armées, Marseille, France.|Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Aix-Marseille Université, UM 63, CNRS 7278, IRD 198, Inserm 1095, AP-HM, Institut Hospitalo-Universitaire (IHU) - Méditerranée Infection, 19-21 Boulevard Jean Moulin, 13005, Marseille, France.|Centre national de référence pour le paludisme, Marseille, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Pradines
authors.affiliation: Unité de Recherche «Génomes et Milieux», Faculté des Sciences et Techniques, Université de Nouakchott Al-Aasriya, Nouveau campus universitaire, BP 5026, Nouakchott, Mauritania.
authors.forename: Ali
authors.initials: A
authors.lastname: Ould Mohamed Salem Boukhary
authors.affiliation: Unité Parasitologie et entomologie, Département des maladies infectieuses, Institut de Recherche Biomédicale des Armées, Marseille, France.|Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Aix-Marseille Université, UM 63, CNRS 7278, IRD 198, Inserm 1095, AP-HM, Institut Hospitalo-Universitaire (IHU) - Méditerranée Infection, 19-21 Boulevard Jean Moulin, 13005, Marseille, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Briolant
authors.affiliation: Unité Parasitologie et entomologie, Département des maladies infectieuses, Institut de Recherche Biomédicale des Armées, Marseille, France.|Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Aix-Marseille Université, UM 63, CNRS 7278, IRD 198, Inserm 1095, AP-HM, Institut Hospitalo-Universitaire (IHU) - Méditerranée Infection, 19-21 Boulevard Jean Moulin, 13005, Marseille, France.
authors.forename: Leonardo K
authors.initials: LK
authors.lastname: Basco
authors.affiliation: Unité Parasitologie et entomologie, Département des maladies infectieuses, Institut de Recherche Biomédicale des Armées, Marseille, France.|Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Aix-Marseille Université, UM 63, CNRS 7278, IRD 198, Inserm 1095, AP-HM, Institut Hospitalo-Universitaire (IHU) - Méditerranée Infection, 19-21 Boulevard Jean Moulin, 13005, Marseille, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Bogreau
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D058070:Asymptomatic Diseases; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D004351:Drug Resistance; D018628:Gene Dosage; D017125:Genes, Protozoan; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology*; D008302:Mali; D008435:Mauritania; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D017422:Sequence Analysis, DNA
chemical_list: D000962:Antimalarials; D016054:DNA, Protozoan
keywords: Amodiaquine; Antifolate drugs; Artemisinin-based combination therapy; Chloroquine; Cross-border malaria; Drug resistance; Lumefantrine; Mauritania; Plasmodium falciparum