title: Absence of correlation between ex vivo susceptibility to doxycycline and pfteQ-pfmdt gene polymorphism in French Guiana.
abstract: BACKGROUND
  In French Guiana, doxycycline is used for both chemoprophylaxis and the treatment of malaria. The presence of isolates with reduced ex vivo susceptibility to doxycycline in French Guiana makes it critical to identify any genetic determinants contributing to the chemosusceptibility level of Plasmodium falciparum to doxycycline, such as pfmdt and pftetQ, which were recently identified as potential molecular markers in African isolates.
  
  
  METHODS
  A Bayesian statistical approach was used to define different ex vivo doxycycline phenotypes. The pfmdt and pftetQ gene copy numbers were quantified by quantitative real-time polymerase chain reaction in 129 P. falciparum isolates collected between 2000 and 2010, and pftetQ, pfrps7, pfssurRNA, and pflsurRNA sequences were analysed after amplification by polymerase chain reaction.
  
  
  RESULTS
  PftetQ and pfmdt copy numbers were not associated with reduced susceptibility to doxycycline in P. falciparum within French Guiana. Sequence analysis of the genes revealed five known single nucleotide polymorphisms. Three new SNPs were identified in the apicoplast ribosomal RNA long sub-unit (pflsurRNA): C740T, A1875C and A1875T. These polymorphisms were not associated with reduced chemosusceptibility to doxycycline.
  
  
  CONCLUSIONS
  The present study does not validate pfmdt and pftetQ genes as molecular markers of decreased susceptibility to doxycycline in P. falciparum isolates in French Guiana.
authors.affiliation: Laboratoire de Parasitologie, Centre National de Référence du Paludisme aux Antilles, Guyane, Institut Pasteur de la Guyane, Cayenne Cedex, France. mariemura@yahoo.fr.|Direction Interarmées du Service de Santé en Guyane, Quartier La Madeleine, BP 6019, 97306, Cayenne Cedex, French Guiana. mariemura@yahoo.fr.
authors.forename: Marie
authors.initials: M
authors.lastname: Mura
authors.affiliation: Laboratoire de Parasitologie, Centre National de Référence du Paludisme aux Antilles, Guyane, Institut Pasteur de la Guyane, Cayenne Cedex, France. sbriolant@pasteur-cayenne.fr.|Direction Interarmées du Service de Santé en Guyane, Quartier La Madeleine, BP 6019, 97306, Cayenne Cedex, French Guiana. sbriolant@pasteur-cayenne.fr.|Institut de Recherche Biomédicale des Armées, BP 73, 91223, Brétigny sur Orge Cedex, France. sbriolant@pasteur-cayenne.fr.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Briolant
authors.affiliation: Laboratoire de Parasitologie, Centre National de Référence du Paludisme aux Antilles, Guyane, Institut Pasteur de la Guyane, Cayenne Cedex, France. ddonato@pasteur-cayenne.fr.
authors.forename: Damien
authors.initials: D
authors.lastname: Donato
authors.affiliation: Laboratoire de Parasitologie, Centre National de Référence du Paludisme aux Antilles, Guyane, Institut Pasteur de la Guyane, Cayenne Cedex, France. bvolney@pasteur-cayenne.fr.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Volney
authors.affiliation: Laboratoire de Parasitologie, Centre National de Référence du Paludisme aux Antilles, Guyane, Institut Pasteur de la Guyane, Cayenne Cedex, France. spelleau@pasteur-cayenne.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Pelleau
authors.affiliation: Laboratoire de Parasitologie, Centre National de Référence du Paludisme aux Antilles, Guyane, Institut Pasteur de la Guyane, Cayenne Cedex, France. lmusset@pasteur-cayenne.fr.
authors.forename: Lise
authors.initials: L
authors.lastname: Musset
authors.affiliation: Laboratoire de Parasitologie, Centre National de Référence du Paludisme aux Antilles, Guyane, Institut Pasteur de la Guyane, Cayenne Cedex, France. eric.legrand@pasteur.fr.|Unité de Recherche Génétique et Génomique des Insectes Vecteurs, Institut Pasteur, 25-28 rue du Dr Roux, 75724, Paris Cedex 15, France. eric.legrand@pasteur.fr.
authors.forename: Eric
authors.initials: E
authors.lastname: Legrand
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D001499:Bayes Theorem; D004318:Doxycycline / Q000494:pharmacology*; D004351:Drug Resistance; D005616:French Guiana; D018628:Gene Dosage; D005819:Genetic Markers; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000962:Antimalarials; D005819:Genetic Markers; D015800:Protozoan Proteins; D004318:Doxycycline