PftetQ and pfmdt copy numbers as predictive molecular markers of decreased ex vivo doxycycline susceptibility in imported Plasmodium falciparum malaria
Identifieur interne : 000162 ( Pmc/Curation ); précédent : 000161; suivant : 000163PftetQ and pfmdt copy numbers as predictive molecular markers of decreased ex vivo doxycycline susceptibility in imported Plasmodium falciparum malaria
Auteurs : Tiphaine Gaillard [France] ; Sébastien Briolant [France] ; Sandrine Houzé [France] ; Meïli Baragatti [France] ; Nathalie Wurtz [France] ; Véronique Hubert [France] ; Morgane Lavina [France] ; Aurélie Pascual [France] ; Christelle Travaillé [France] ; Jacques Le Bras [France] ; Bruno Pradines [France]Source :
- Malaria Journal [ 1475-2875 ] ; 2013.
Abstract
The objective of this study was to evaluate the distribution of a series of independent doxycycline inhibitory concentration 50% (IC50) values to validate the trimodal distribution previously described and to validate the use of the
Doxycycline IC50 values, from 484 isolates obtained at the French National Reference Centre for Imported Malaria (Paris) between January 2006 and December 2010, were analysed for the first time by a Bayesian mixture modelling approach to distinguish the different
The existence of at least three doxycycline phenotypes was demonstrated. The mean doxycycline IC50 was significantly higher in the group with a
Copy numbers of
Url:
DOI: 10.1186/1475-2875-12-414
PubMed: 24225377
PubMed Central: 3831056
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xml:lang="fr">France</country><wicri:regionArea>Unité Mixte de Recherche 216 IRD, Université Paris Descartes, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I6">Centre National de Référence du Paludisme, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Centre National de Référence du Paludisme, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Baragatti, Meili" sort="Baragatti, Meili" uniqKey="Baragatti M" first="Meïli" last="Baragatti">Meïli Baragatti</name><affiliation wicri:level="1"><nlm:aff id="I7">Unité de Recherche Mixte Sup-Agro-Inra MISTEA, SupAgro, Montpellier, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Recherche Mixte Sup-Agro-Inra MISTEA, SupAgro, Montpellier</wicri:regionArea></affiliation></author><author><name sortKey="Wurtz, Nathalie" sort="Wurtz, Nathalie" uniqKey="Wurtz N" first="Nathalie" last="Wurtz">Nathalie Wurtz</name><affiliation wicri:level="1"><nlm:aff id="I1">Unité de Parasitologie, Institut de Recherche Biomédicale des Armées, Marseille, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Parasitologie, Institut de Recherche Biomédicale des Armées, Marseille</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I2">Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, Marseille, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, Marseille</wicri:regionArea></affiliation></author><author><name sortKey="Hubert, Veronique" sort="Hubert, Veronique" uniqKey="Hubert V" first="Véronique" last="Hubert">Véronique Hubert</name><affiliation wicri:level="1"><nlm:aff id="I4">Laboratoire de Parasitologie-Mycologie, Hôpital Bichat-Claude Bernard, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Parasitologie-Mycologie, Hôpital Bichat-Claude Bernard, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I6">Centre National de Référence du Paludisme, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Centre National de Référence du Paludisme, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Lavina, Morgane" sort="Lavina, Morgane" uniqKey="Lavina M" first="Morgane" last="Lavina">Morgane Lavina</name><affiliation wicri:level="1"><nlm:aff id="I1">Unité de Parasitologie, Institut de Recherche Biomédicale des Armées, Marseille, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Parasitologie, Institut de Recherche Biomédicale des Armées, Marseille</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I2">Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, Marseille, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, Marseille</wicri:regionArea></affiliation></author><author><name sortKey="Pascual, Aurelie" sort="Pascual, Aurelie" uniqKey="Pascual A" first="Aurélie" last="Pascual">Aurélie Pascual</name><affiliation wicri:level="1"><nlm:aff id="I1">Unité de Parasitologie, Institut de Recherche Biomédicale des Armées, Marseille, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Parasitologie, Institut de Recherche Biomédicale des Armées, Marseille</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I2">Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, Marseille, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, Marseille</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I6">Centre National de Référence du Paludisme, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Centre National de Référence du Paludisme, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Travaille, Christelle" sort="Travaille, Christelle" uniqKey="Travaille C" first="Christelle" last="Travaillé">Christelle Travaillé</name><affiliation wicri:level="1"><nlm:aff id="I8">Unité de Recherche Mixte MD3, Institut de Recherche Biomédicale des Armées, Marseille, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Recherche Mixte MD3, Institut de Recherche Biomédicale des Armées, Marseille</wicri:regionArea></affiliation></author><author><name sortKey="Le Bras, Jacques" sort="Le Bras, Jacques" uniqKey="Le Bras J" first="Jacques" last="Le Bras">Jacques Le Bras</name><affiliation wicri:level="1"><nlm:aff id="I4">Laboratoire de Parasitologie-Mycologie, Hôpital Bichat-Claude Bernard, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Parasitologie-Mycologie, Hôpital Bichat-Claude Bernard, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I5">Unité Mixte de Recherche 216 IRD, Université Paris Descartes, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Mixte de Recherche 216 IRD, Université Paris Descartes, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I6">Centre National de Référence du Paludisme, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Centre National de Référence du Paludisme, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Pradines, Bruno" sort="Pradines, Bruno" uniqKey="Pradines B" first="Bruno" last="Pradines">Bruno Pradines</name><affiliation wicri:level="1"><nlm:aff id="I1">Unité de Parasitologie, Institut de Recherche Biomédicale des Armées, Marseille, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Parasitologie, Institut de Recherche Biomédicale des Armées, Marseille</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I2">Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, Marseille, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, Marseille</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I6">Centre National de Référence du Paludisme, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Centre National de Référence du Paludisme, Paris</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24225377</idno><idno type="pmc">3831056</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831056</idno><idno type="RBID">PMC:3831056</idno><idno type="doi">10.1186/1475-2875-12-414</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000164</idno><idno type="wicri:Area/Pmc/Curation">000162</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">PftetQ and pfmdt copy numbers as predictive molecular markers of decreased ex vivo doxycycline susceptibility in imported Plasmodium falciparum malaria</title><author><name sortKey="Gaillard, Tiphaine" sort="Gaillard, Tiphaine" uniqKey="Gaillard T" first="Tiphaine" last="Gaillard">Tiphaine Gaillard</name><affiliation wicri:level="1"><nlm:aff id="I1">Unité de Parasitologie, Institut de Recherche Biomédicale des Armées, Marseille, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Parasitologie, Institut de Recherche Biomédicale des Armées, Marseille</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I2">Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, Marseille, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, Marseille</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I3">Fédération des Laboratoires, Hôpital d’Instruction des Armées Saint Anne, Toulon, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Fédération des Laboratoires, Hôpital d’Instruction des Armées Saint Anne, Toulon</wicri:regionArea></affiliation></author><author><name sortKey="Briolant, Sebastien" sort="Briolant, Sebastien" uniqKey="Briolant S" first="Sébastien" last="Briolant">Sébastien Briolant</name><affiliation wicri:level="1"><nlm:aff id="I1">Unité de Parasitologie, Institut de Recherche Biomédicale des Armées, Marseille, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Parasitologie, Institut de Recherche Biomédicale des Armées, Marseille</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I2">Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, Marseille, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, Marseille</wicri:regionArea></affiliation></author><author><name sortKey="Houze, Sandrine" sort="Houze, Sandrine" uniqKey="Houze S" first="Sandrine" last="Houzé">Sandrine Houzé</name><affiliation wicri:level="1"><nlm:aff id="I4">Laboratoire de Parasitologie-Mycologie, Hôpital Bichat-Claude Bernard, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Parasitologie-Mycologie, Hôpital Bichat-Claude Bernard, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I5">Unité Mixte de Recherche 216 IRD, Université Paris Descartes, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Mixte de Recherche 216 IRD, Université Paris Descartes, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I6">Centre National de Référence du Paludisme, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Centre National de Référence du Paludisme, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Baragatti, Meili" sort="Baragatti, Meili" uniqKey="Baragatti M" first="Meïli" last="Baragatti">Meïli Baragatti</name><affiliation wicri:level="1"><nlm:aff id="I7">Unité de Recherche Mixte Sup-Agro-Inra MISTEA, SupAgro, Montpellier, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Recherche Mixte Sup-Agro-Inra MISTEA, SupAgro, Montpellier</wicri:regionArea></affiliation></author><author><name sortKey="Wurtz, Nathalie" sort="Wurtz, Nathalie" uniqKey="Wurtz N" first="Nathalie" last="Wurtz">Nathalie Wurtz</name><affiliation wicri:level="1"><nlm:aff id="I1">Unité de Parasitologie, Institut de Recherche Biomédicale des Armées, Marseille, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Parasitologie, Institut de Recherche Biomédicale des Armées, Marseille</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I2">Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, Marseille, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, Marseille</wicri:regionArea></affiliation></author><author><name sortKey="Hubert, Veronique" sort="Hubert, Veronique" uniqKey="Hubert V" first="Véronique" last="Hubert">Véronique Hubert</name><affiliation wicri:level="1"><nlm:aff id="I4">Laboratoire de Parasitologie-Mycologie, Hôpital Bichat-Claude Bernard, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Parasitologie-Mycologie, Hôpital Bichat-Claude Bernard, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I6">Centre National de Référence du Paludisme, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Centre National de Référence du Paludisme, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Lavina, Morgane" sort="Lavina, Morgane" uniqKey="Lavina M" first="Morgane" last="Lavina">Morgane Lavina</name><affiliation wicri:level="1"><nlm:aff id="I1">Unité de Parasitologie, Institut de Recherche Biomédicale des Armées, Marseille, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Parasitologie, Institut de Recherche Biomédicale des Armées, Marseille</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I2">Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, Marseille, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, Marseille</wicri:regionArea></affiliation></author><author><name sortKey="Pascual, Aurelie" sort="Pascual, Aurelie" uniqKey="Pascual A" first="Aurélie" last="Pascual">Aurélie Pascual</name><affiliation wicri:level="1"><nlm:aff id="I1">Unité de Parasitologie, Institut de Recherche Biomédicale des Armées, Marseille, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Parasitologie, Institut de Recherche Biomédicale des Armées, Marseille</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I2">Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, Marseille, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, Marseille</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I6">Centre National de Référence du Paludisme, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Centre National de Référence du Paludisme, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Travaille, Christelle" sort="Travaille, Christelle" uniqKey="Travaille C" first="Christelle" last="Travaillé">Christelle Travaillé</name><affiliation wicri:level="1"><nlm:aff id="I8">Unité de Recherche Mixte MD3, Institut de Recherche Biomédicale des Armées, Marseille, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Recherche Mixte MD3, Institut de Recherche Biomédicale des Armées, Marseille</wicri:regionArea></affiliation></author><author><name sortKey="Le Bras, Jacques" sort="Le Bras, Jacques" uniqKey="Le Bras J" first="Jacques" last="Le Bras">Jacques Le Bras</name><affiliation wicri:level="1"><nlm:aff id="I4">Laboratoire de Parasitologie-Mycologie, Hôpital Bichat-Claude Bernard, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Parasitologie-Mycologie, Hôpital Bichat-Claude Bernard, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I5">Unité Mixte de Recherche 216 IRD, Université Paris Descartes, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Mixte de Recherche 216 IRD, Université Paris Descartes, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I6">Centre National de Référence du Paludisme, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Centre National de Référence du Paludisme, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Pradines, Bruno" sort="Pradines, Bruno" uniqKey="Pradines B" first="Bruno" last="Pradines">Bruno Pradines</name><affiliation wicri:level="1"><nlm:aff id="I1">Unité de Parasitologie, Institut de Recherche Biomédicale des Armées, Marseille, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Parasitologie, Institut de Recherche Biomédicale des Armées, Marseille</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I2">Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, Marseille, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, Marseille</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I6">Centre National de Référence du Paludisme, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Centre National de Référence du Paludisme, Paris</wicri:regionArea></affiliation></author></analytic><series><title level="j">Malaria Journal</title><idno type="eISSN">1475-2875</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>The objective of this study was to evaluate the distribution of a series of independent doxycycline inhibitory concentration 50% (IC<sub>50</sub>) values to validate the trimodal distribution previously described and to validate the use of the <italic>pftetQ</italic> and <italic>pfmdt</italic> genes as molecular markers of decreased <italic>in vitro</italic> doxycycline susceptibility in <italic>Plasmodium falciparum</italic> malaria.</p></sec><sec><title>Methods</title><p>Doxycycline IC<sub>50</sub> values, from 484 isolates obtained at the French National Reference Centre for Imported Malaria (Paris) between January 2006 and December 2010, were analysed for the first time by a Bayesian mixture modelling approach to distinguish the different <italic>in vitro</italic> phenotypic groups by their IC<sub>50</sub> values. Quantitative real-time polymerase chain reaction was used to evaluate the <italic>pftetQ</italic> and <italic>pfmdt</italic> copy numbers of 89 African <italic>P. falciparum</italic> isolates that were randomly chosen from the phenotypic groups.</p></sec><sec><title>Results</title><p>The existence of at least three doxycycline phenotypes was demonstrated. The mean doxycycline IC<sub>50</sub> was significantly higher in the group with a <italic>pftetQ</italic> copy number >1 compared to the group with a <italic>pftetQ</italic> copy number = 1 (33.17 μM <italic>versus</italic> 17.23 μM) and the group with a <italic>pfmdt</italic> copy number >1 (28.28 μM <italic>versus</italic> 16.11 μM). There was a significant difference between the combined low and medium doxycycline IC<sub>50</sub> group and the high IC<sub>50</sub> group in terms of the per cent of isolates with one or more copy numbers of the <italic>pftetQ</italic> gene (0% <italic>versus</italic> 20.69%) or <italic>pfmdt</italic> gene (8.33% <italic>versus</italic> 37.93%). In the logistic regression model, the <italic>pfmdt</italic> and <italic>pftetQ</italic> copy numbers >1 (odds ratio = 4.65 and 11.47) were independently associated with the high IC<sub>50</sub> group.</p></sec><sec><title>Conclusions</title><p>Copy numbers of <italic>pftetQ</italic> and <italic>pfmdt</italic> are potential predictive molecular markers of decreased susceptibility to doxycycline.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Pang, L" uniqKey="Pang L">L Pang</name></author><author><name sortKey="Limsomwong, N" uniqKey="Limsomwong N">N Limsomwong</name></author><author><name sortKey="Singharaj, P" uniqKey="Singharaj P">P Singharaj</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wallace, Mr" uniqKey="Wallace M">MR Wallace</name></author><author><name sortKey="Sharp, Tw" uniqKey="Sharp T">TW Sharp</name></author><author><name 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Malar J</journal-id><journal-id journal-id-type="iso-abbrev">Malar. J</journal-id><journal-title-group><journal-title>Malaria Journal</journal-title></journal-title-group><issn pub-type="epub">1475-2875</issn><publisher><publisher-name>BioMed Central</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24225377</article-id><article-id pub-id-type="pmc">3831056</article-id><article-id pub-id-type="publisher-id">1475-2875-12-414</article-id><article-id pub-id-type="doi">10.1186/1475-2875-12-414</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research</subject></subj-group></article-categories><title-group><article-title>PftetQ and pfmdt copy numbers as predictive molecular markers of decreased ex vivo doxycycline susceptibility in imported Plasmodium falciparum malaria</article-title></title-group><contrib-group><contrib contrib-type="author" id="A1"><name><surname>Gaillard</surname><given-names>Tiphaine</given-names></name><xref ref-type="aff" rid="I1">1</xref><xref ref-type="aff" rid="I2">2</xref><xref ref-type="aff" rid="I3">3</xref><email>tiphaine.rousselgaillard@gmail.com</email></contrib><contrib contrib-type="author" id="A2"><name><surname>Briolant</surname><given-names>Sébastien</given-names></name><xref ref-type="aff" rid="I1">1</xref><xref ref-type="aff" rid="I2">2</xref><email>sbriolant@wanadoo.fr</email></contrib><contrib contrib-type="author" id="A3"><name><surname>Houzé</surname><given-names>Sandrine</given-names></name><xref ref-type="aff" rid="I4">4</xref><xref ref-type="aff" rid="I5">5</xref><xref ref-type="aff" rid="I6">6</xref><email>sandrine.houze@bch.aphp.fr</email></contrib><contrib contrib-type="author" id="A4"><name><surname>Baragatti</surname><given-names>Meïli</given-names></name><xref ref-type="aff" rid="I7">7</xref><email>Meili.baragatti@supagro.inra.fr</email></contrib><contrib contrib-type="author" id="A5"><name><surname>Wurtz</surname><given-names>Nathalie</given-names></name><xref ref-type="aff" rid="I1">1</xref><xref ref-type="aff" rid="I2">2</xref><email>nathalie_wurtz@yahoo.fr</email></contrib><contrib contrib-type="author" id="A6"><name><surname>Hubert</surname><given-names>Véronique</given-names></name><xref ref-type="aff" rid="I4">4</xref><xref ref-type="aff" rid="I6">6</xref><email>hubevero@yahoo.fr</email></contrib><contrib contrib-type="author" id="A7"><name><surname>Lavina</surname><given-names>Morgane</given-names></name><xref ref-type="aff" rid="I1">1</xref><xref ref-type="aff" rid="I2">2</xref><email>morgane.lavina@laposte.net</email></contrib><contrib contrib-type="author" id="A8"><name><surname>Pascual</surname><given-names>Aurélie</given-names></name><xref ref-type="aff" rid="I1">1</xref><xref ref-type="aff" rid="I2">2</xref><xref ref-type="aff" rid="I6">6</xref><email>aureliepascual@hotmail.com</email></contrib><contrib contrib-type="author" id="A9"><name><surname>Travaillé</surname><given-names>Christelle</given-names></name><xref ref-type="aff" rid="I8">8</xref><email>christelletravaille@hotmail.fr</email></contrib><contrib contrib-type="author" id="A10"><name><surname>Le Bras</surname><given-names>Jacques</given-names></name><xref ref-type="aff" rid="I4">4</xref><xref ref-type="aff" rid="I5">5</xref><xref ref-type="aff" rid="I6">6</xref><email>jacques.lebras@gmail.com</email></contrib><contrib contrib-type="author" corresp="yes" id="A11"><name><surname>Pradines</surname><given-names>Bruno</given-names></name><xref ref-type="aff" rid="I1">1</xref><xref ref-type="aff" rid="I2">2</xref><xref ref-type="aff" rid="I6">6</xref><email>bruno.pradines@free.fr</email></contrib><on-behalf-of>The French National Reference Centre for Imported Malaria Study Group<xref ref-type="corresp" rid="d33e117"></xref></on-behalf-of></contrib-group><aff id="I1"><label>1</label>Unité de Parasitologie, Institut de Recherche Biomédicale des Armées, Marseille, France</aff><aff id="I2"><label>2</label>Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Aix Marseille Université, Marseille, France</aff><aff id="I3"><label>3</label>Fédération des Laboratoires, Hôpital d’Instruction des Armées Saint Anne, Toulon, France</aff><aff id="I4"><label>4</label>Laboratoire de Parasitologie-Mycologie, Hôpital Bichat-Claude Bernard, Paris, France</aff><aff id="I5"><label>5</label>Unité Mixte de Recherche 216 IRD, Université Paris Descartes, Paris, France</aff><aff id="I6"><label>6</label>Centre National de Référence du Paludisme, Paris, France</aff><aff id="I7"><label>7</label>Unité de Recherche Mixte Sup-Agro-Inra MISTEA, SupAgro, Montpellier, France</aff><aff id="I8"><label>8</label>Unité de Recherche Mixte MD3, Institut de Recherche Biomédicale des Armées, Marseille, France</aff><author-notes><corresp id="d33e117">The French National Reference Centre for Imported Malaria Study Group</corresp></author-notes><pub-date pub-type="collection"><year>2013</year></pub-date><pub-date pub-type="epub"><day>14</day><month>11</month><year>2013</year></pub-date><volume>12</volume><fpage>414</fpage><lpage>414</lpage><history><date date-type="received"><day>2</day><month>7</month><year>2013</year></date><date date-type="accepted"><day>10</day><month>11</month><year>2013</year></date></history><permissions><copyright-statement>Copyright © 2013 Gaillard et al.; licensee BioMed Central Ltd.</copyright-statement><copyright-year>2013</copyright-year><copyright-holder>Gaillard et al.; licensee BioMed Central Ltd.</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/2.0"><license-p>This is an open access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/2.0">http://creativecommons.org/licenses/by/2.0</ext-link>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><self-uri xlink:href="http://www.malariajournal.com/content/12/1/414"></self-uri><abstract><sec><title>Background</title><p>The objective of this study was to evaluate the distribution of a series of independent doxycycline inhibitory concentration 50% (IC<sub>50</sub>) values to validate the trimodal distribution previously described and to validate the use of the <italic>pftetQ</italic> and <italic>pfmdt</italic> genes as molecular markers of decreased <italic>in vitro</italic> doxycycline susceptibility in <italic>Plasmodium falciparum</italic> malaria.</p></sec><sec><title>Methods</title><p>Doxycycline IC<sub>50</sub> values, from 484 isolates obtained at the French National Reference Centre for Imported Malaria (Paris) between January 2006 and December 2010, were analysed for the first time by a Bayesian mixture modelling approach to distinguish the different <italic>in vitro</italic> phenotypic groups by their IC<sub>50</sub> values. Quantitative real-time polymerase chain reaction was used to evaluate the <italic>pftetQ</italic> and <italic>pfmdt</italic> copy numbers of 89 African <italic>P. falciparum</italic> isolates that were randomly chosen from the phenotypic groups.</p></sec><sec><title>Results</title><p>The existence of at least three doxycycline phenotypes was demonstrated. The mean doxycycline IC<sub>50</sub> was significantly higher in the group with a <italic>pftetQ</italic> copy number >1 compared to the group with a <italic>pftetQ</italic> copy number = 1 (33.17 μM <italic>versus</italic> 17.23 μM) and the group with a <italic>pfmdt</italic> copy number >1 (28.28 μM <italic>versus</italic> 16.11 μM). There was a significant difference between the combined low and medium doxycycline IC<sub>50</sub> group and the high IC<sub>50</sub> group in terms of the per cent of isolates with one or more copy numbers of the <italic>pftetQ</italic> gene (0% <italic>versus</italic> 20.69%) or <italic>pfmdt</italic> gene (8.33% <italic>versus</italic> 37.93%). In the logistic regression model, the <italic>pfmdt</italic> and <italic>pftetQ</italic> copy numbers >1 (odds ratio = 4.65 and 11.47) were independently associated with the high IC<sub>50</sub> group.</p></sec><sec><title>Conclusions</title><p>Copy numbers of <italic>pftetQ</italic> and <italic>pfmdt</italic> are potential predictive molecular markers of decreased susceptibility to doxycycline.</p></sec></abstract><kwd-group><kwd>Malaria</kwd><kwd><italic>Plasmodium falciparum</italic></kwd><kwd>Anti-malarial</kwd><kwd><italic>In vitro</italic></kwd><kwd>Resistance</kwd><kwd>Molecular marker</kwd><kwd>Doxycycline</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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