title: Absence of association between Plasmodium falciparum small sub-unit ribosomal RNA gene mutations and in vitro decreased susceptibility to doxycycline.
abstract: BACKGROUND
  Doxycycline is an antibiotic used in combination with quinine or artesunate for malaria treatment or alone for malaria chemoprophylaxis. Recently, one prophylactic failure has been reported, and several studies have highlighted in vitro doxycycline decreased susceptibility in Plasmodium falciparum isolates from different areas. The genetic markers that contribute to detecting and monitoring the susceptibility of P. falciparum to doxycycline, the pfmdt and pftetQ genes, have recently been identified. However, these markers are not sufficient to explain in vitro decreased susceptibility of P. falciparum to doxycycline. In this paper, the association between polymorphism of the small sub-unit ribosomal RNA apicoplastic gene pfssrRNA (PFC10_API0057) and in vitro susceptibilities of P. falciparum isolates to doxycycline were investigated.
  
  
  METHODS
  Doxycycline IC50 determinations using the hypoxanthine uptake inhibition assay were performed on 178 African and Thai P. falciparum isolates. The polymorphism of pfssrRNA was investigated in these samples by standard PCR followed by sequencing.
  
  
  RESULTS
  No point mutations were found in pfssrRNA in the Thai or African isolates, regardless of the determined IC50 values.
  
  
  CONCLUSIONS
  The pfssrRNA gene is not associated with in vitro decreased susceptibility of P. falciparum to doxycycline. Identifying new in vitro molecular markers associated with reduced susceptibility is needed, to survey the emergence of doxycycline resistance.
authors.affiliation: Unité de Parasitologie, Département d'Infectiologie de Terrain, Institut de Recherche Biomédicale des Armées, Marseille, France. tiphaine.rousselgaillard@gmail.com.|Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, Aix Marseille Université, UM 63, CNRS 7278, IRD 198, Inserm 1095, Marseille, France. tiphaine.rousselgaillard@gmail.com.|Fédération des Laboratoires, Hôpital d'Instruction des Armées Saint Anne, Toulon, France. tiphaine.rousselgaillard@gmail.com.
authors.forename: Tiphaine
authors.initials: T
authors.lastname: Gaillard
authors.affiliation: Unité de Parasitologie, Département d'Infectiologie de Terrain, Institut de Recherche Biomédicale des Armées, Marseille, France. nathalie_wurtz@yahoo.fr.|Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, Aix Marseille Université, UM 63, CNRS 7278, IRD 198, Inserm 1095, Marseille, France. nathalie_wurtz@yahoo.fr.|Centre National de Référence du Paludisme, Marseille, France. nathalie_wurtz@yahoo.fr.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Wurtz
authors.affiliation: Laboratoire de Parasitologie-Mycologie, Centre National de Référence du Paludisme, APHP, Hôpital Bichat-Claude Bernard, Paris, France. sandrine.houze@aphp.fr.|IRD UMR216, Mère et enfant face aux infections tropicales, Paris, France. sandrine.houze@aphp.fr.|PRES Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, Paris, France. sandrine.houze@aphp.fr.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Houzé
authors.affiliation: Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sod, Thailand. poo@shoklo-unit.com.
authors.forename: Kanlaya
authors.initials: K
authors.lastname: Sriprawat
authors.affiliation: Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sod, Thailand. neng@shoklo-unit.com.
authors.forename: Chirapat
authors.initials: C
authors.lastname: Wangsing
authors.affiliation: Laboratoire de Parasitologie-Mycologie, Centre National de Référence du Paludisme, APHP, Hôpital Bichat-Claude Bernard, Paris, France. hubevero@yahoo.fr.|PRES Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, Paris, France. hubevero@yahoo.fr.
authors.forename: Véronique
authors.initials: V
authors.lastname: Hubert
authors.affiliation: Laboratoire de Parasitologie-Mycologie, Centre National de Référence du Paludisme, APHP, Hôpital Bichat-Claude Bernard, Paris, France. jacques.lebras@gmail.com.|IRD UMR216, Mère et enfant face aux infections tropicales, Paris, France. jacques.lebras@gmail.com.|PRES Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, Paris, France. jacques.lebras@gmail.com.
authors.forename: Jacques
authors.initials: J
authors.lastname: Lebras
authors.affiliation: Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sod, Thailand. francois@tropmedres.ac.|Centre for Tropical Medicine, University of Oxford, Oxford, UK. francois@tropmedres.ac.
authors.forename: François
authors.initials: F
authors.lastname: Nosten
authors.affiliation: Unité de Parasitologie, Département d'Infectiologie de Terrain, Institut de Recherche Biomédicale des Armées, Marseille, France. sbriolant@wanadoo.fr.|Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, Aix Marseille Université, UM 63, CNRS 7278, IRD 198, Inserm 1095, Marseille, France. sbriolant@wanadoo.fr.|Direction Inter-Armées du Service de Santé, Cayenne, French Guiana. sbriolant@wanadoo.fr.|Laboratoire de Parasitologie, Institut Pasteur de la Guyane, Cayenne, French Guiana. sbriolant@wanadoo.fr.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Briolant
authors.affiliation: Unité de Parasitologie, Département d'Infectiologie de Terrain, Institut de Recherche Biomédicale des Armées, Marseille, France. bruno.pradines@free.fr.|Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, Aix Marseille Université, UM 63, CNRS 7278, IRD 198, Inserm 1095, Marseille, France. bruno.pradines@free.fr.|Centre National de Référence du Paludisme, Marseille, France. bruno.pradines@free.fr.|Unité de Parasitologie et d'Entomologie, Département des Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, Brétigny sur Orge, France. bruno.pradines@free.fr.
authors.forename: Bruno
authors.initials: B
authors.lastname: Pradines
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D004318:Doxycycline / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics*; D017125:Genes, Protozoan / Q000235:genetics*; D020459:Genes, rRNA / Q000235:genetics*; D006801:Humans; D020128:Inhibitory Concentration 50; D016778:Malaria, Falciparum / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics*
chemical_list: D000962:Antimalarials; D004318:Doxycycline