{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:54:37Z","timestamp":1791176077908,"version":"4.1.0"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Malar J"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The objective of this study was to evaluate the distribution of a series of independent doxycycline inhibitory concentration 50% (IC<jats:sub>50<\/jats:sub>) values to validate the trimodal distribution previously described and to validate the use of the<jats:italic>pftetQ<\/jats:italic>and<jats:italic>pfmdt<\/jats:italic>genes as molecular markers of decreased<jats:italic>in vitro<\/jats:italic>doxycycline susceptibility in<jats:italic>Plasmodium falciparum<\/jats:italic>malaria.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Doxycycline IC<jats:sub>50<\/jats: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<jats:italic>in vitro<\/jats:italic>phenotypic groups by their IC<jats:sub>50<\/jats:sub>values. Quantitative real-time polymerase chain reaction was used to evaluate the<jats:italic>pftetQ<\/jats:italic>and<jats:italic>pfmdt<\/jats:italic>copy numbers of 89 African<jats:italic>P. falciparum<\/jats:italic>isolates that were randomly chosen from the phenotypic groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The existence of at least three doxycycline phenotypes was demonstrated. The mean doxycycline IC<jats:sub>50<\/jats:sub>was significantly higher in the group with a<jats:italic>pftetQ<\/jats:italic>copy number &gt;1 compared to the group with a<jats:italic>pftetQ<\/jats:italic>copy number\u2009=\u20091 (33.17\u00a0\u03bcM<jats:italic>versus<\/jats:italic>17.23\u00a0\u03bcM) and the group with a<jats:italic>pfmdt<\/jats:italic>copy number &gt;1 (28.28\u00a0\u03bcM<jats:italic>versus<\/jats:italic>16.11\u00a0\u03bcM). There was a significant difference between the combined low and medium doxycycline IC<jats:sub>50<\/jats:sub>group and the high IC<jats:sub>50<\/jats:sub>group in terms of the per cent of isolates with one or more copy numbers of the<jats:italic>pftetQ<\/jats:italic>gene (0%<jats:italic>versus<\/jats:italic>20.69%) or<jats:italic>pfmdt<\/jats:italic>gene (8.33%<jats:italic>versus<\/jats:italic>37.93%). In the logistic regression model, the<jats:italic>pfmdt<\/jats:italic>and<jats:italic>pftetQ<\/jats:italic>copy numbers &gt;1 (odds ratio\u2009=\u20094.65 and 11.47) were independently associated with the high IC<jats:sub>50<\/jats:sub>group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Copy numbers of<jats:italic>pftetQ<\/jats:italic>and<jats:italic>pfmdt<\/jats:italic>are potential predictive molecular markers of decreased susceptibility to doxycycline.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1475-2875-12-414","type":"journal-article","created":{"date-parts":[[2013,11,14]],"date-time":"2013-11-14T02:01:50Z","timestamp":1384394510000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["PftetQ and pfmdt copy numbers as predictive molecular markers of decreased ex vivo doxycycline susceptibility in imported Plasmodium falciparum malaria"],"prefix":"10.1186","volume":"12","author":[{"given":"Tiphaine","family":"Gaillard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Briolant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Houz\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Me\u00efli","family":"Baragatti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Wurtz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Hubert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgane","family":"Lavina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Pascual","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christelle","family":"Travaill\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Le Bras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Pradines","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The French National Reference Centre for Imported Malaria Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,11,14]]},"reference":[{"key":"3012_CR1","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.medmal.2007.11.009","volume":"38","author":"Soci\u00e9t\u00e9 de Pathologie Infectieuse de Langue Fran\u00e7aise, Coll\u00e8ge des Universitaires de Maladies Infectieuses et Tropicales, Soci\u00e9t\u00e9 de M\u00e9decine des Arm\u00e9es, Soci\u00e9t\u00e9 Fran\u00e7aise de Parasitologie, Soci\u00e9t\u00e9 Fran\u00e7aise de P\u00e9diatrie, Soci\u00e9t\u00e9 de M\u00e9decine des Voyages, Soci\u00e9t\u00e9 de Pathologie Exotique, Soci\u00e9t\u00e9 de R\u00e9animation de Langue Fran\u00e7aise","year":"2008","unstructured":"Soci\u00e9t\u00e9 de Pathologie Infectieuse de Langue Fran\u00e7aise, Coll\u00e8ge des Universitaires de Maladies Infectieuses et Tropicales, Soci\u00e9t\u00e9 de M\u00e9decine des Arm\u00e9es, Soci\u00e9t\u00e9 Fran\u00e7aise de Parasitologie, Soci\u00e9t\u00e9 Fran\u00e7aise de P\u00e9diatrie, Soci\u00e9t\u00e9 de M\u00e9decine des Voyages, Soci\u00e9t\u00e9 de Pathologie Exotique, Soci\u00e9t\u00e9 de R\u00e9animation de Langue Fran\u00e7aise: Management and prevention of imported Plasmodium falciparum malaria: recommendations for clinical practice 2007 (revision 2007 of the 1999 consensus conference). 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