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Absence of correlation between ex vivo susceptibility to doxycycline and pfteQ–pfmdt gene polymorphism in French Guiana

Authors :
Lise Musset
Eric Legrand
Damien Donato
Marie Mura
Béatrice Volney
Sébastien Briolant
Stéphane Pelleau
Institut Pasteur de la Guyane
Réseau International des Instituts Pasteur (RIIP)
Direction Interarmées du Service de Santé en Guyane
Institut de Recherche Biomédicale des Armées (IRBA)
This study benefited from European commission grant REGPOT-CT-2011-285837-STRonGer within the FP7 program me and the French Ministry of Health (InVS agency, Paris)
European Project: 285837,EC:FP7:REGPOT,FP7-REGPOT-2011-1,STRONGER(2011)
Institut de Recherche des Armées
European Project : 285837, EC:FP7:REGPOT, FP7-REGPOT-2011-1, STRONGER(2011)
Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA)
Source :
Malaria Journal, Malaria Journal, BioMed Central, 2015, 14 (1), pp.286. ⟨10.1186/s12936-015-0788-y⟩, Malaria Journal, BioMed Central, 2015, 14 (1), pp.286. <10.1186/s12936-015-0788-y>, Malaria Journal, 2015, 14 (1), pp.286. ⟨10.1186/s12936-015-0788-y⟩
Publication Year :
2015
Publisher :
HAL CCSD, 2015.

Abstract

International audience; 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. falcipa-rum 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. falci-parum 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.

Details

Language :
English
ISSN :
14752875
Database :
OpenAIRE
Journal :
Malaria Journal, Malaria Journal, BioMed Central, 2015, 14 (1), pp.286. ⟨10.1186/s12936-015-0788-y⟩, Malaria Journal, BioMed Central, 2015, 14 (1), pp.286. <10.1186/s12936-015-0788-y>, Malaria Journal, 2015, 14 (1), pp.286. ⟨10.1186/s12936-015-0788-y⟩
Accession number :
edsair.doi.dedup.....20a0be0c63377b7e20079307eab4d8db
Full Text :
https://doi.org/10.1186/s12936-015-0788-y⟩