Limited polymorphisms in k13 gene in Plasmodium falciparum isolates from Dakar, Senegal in 2012–2013

Malaria Journal

Research

Bruno Pradines¹  Boubacar Wade²  Rémy Amalvict³  Marylin Torrentino-Madamet³  Nicolas Benoit³  Bécaye Fall⁴  Yaya Diemé⁴  Didier Ménard⁵  Pierre Dionne⁶  Kadidiatou Ba Fall⁷  Aminata Nakoulima⁸  Bakary Diatta⁹  Mansour Fall⁹  Cheikhou Camara^1,10 

[1] Aix Marseille Université, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, 1095, Inserm, Marseille, France;Centre National de Référence du Paludisme, Marseille, France;Laboratoire d’Etude de la Chimiosensibilité du Paludisme, Fédération des Laboratoires, Hôpital Principal de Dakar, Dakar, Sénégal;Unité de Parasitologie et d’Entomologie, Département des Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, Brétigny sur Orge, Bretigny sur Orge, France;Chefferie, Hôpital Principal de Dakar, Dakar, Sénégal;Equipe Résidente de Recherche en Infectiologie Tropicale, Institut de Recherche Biomédicale des Armées, Hôpital d’Instruction des Armées, Marseille, France;Aix Marseille Université, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, 1095, Inserm, Marseille, France;Centre National de Référence du Paludisme, Marseille, France;Laboratoire d’Etude de la Chimiosensibilité du Paludisme, Fédération des Laboratoires, Hôpital Principal de Dakar, Dakar, Sénégal;Malaria Molecular Epidemiology Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia;Maternité Hôpital Principal de Dakar, Dakar, Sénégal;Service de Pathologie Infectieuse, Hôpital Principal de Dakar, Dakar, Sénégal;Service de Pédiatrie, Hôpital Principal de Dakar, Dakar, Sénégal;Service de réanimation Médicale, Hôpital Principal de Dakar, Dakar, Sénégal;Service des Urgences, Hôpital Principal de Dakar, Dakar, Sénégal;

关键词: Malaria;    Plasmodium falciparum;    Anti-malarial drug;    Resistance;    Molecular marker;    artemisinin;    K13-propeller;    Senegal;   

DOI  :  10.1186/1475-2875-13-472

 received in 2014-11-05, accepted in 2014-11-28,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundThe emergence of Plasmodium falciparum resistance to artemisinin and its derivatives, manifested as delayed parasite clearance following the treatment, has developed in Southeast Asia. The spread of resistance to artemisinin from Asia to Africa may be catastrophic for malaria control and elimination worldwide. Recently, mutations in the propeller domain of the Kelch 13 (k13) gene (PF3D71343700) were associated with in vitro resistance to artemisinin and with delayed clearance after artemisinin treatment in southern Asia. The aim of the study was to characterize the genetic variability of k13 and to evaluate the molecular resistance to artemisinin for the first time in Senegal.MethodsPlasmodium falciparum isolates were collected from 138 malaria patients in Dakar and its districts during the rainy season of October 2012 to January 2013 at the Hôpital Principal de Dakar. The k13 gene was amplified using nested PCR and sequenced.ResultsA very limited variability within the k13 gene in Senegalese P. falciparum isolates was identified. No polymorphism was detected in the six k13-propeller blades. Only two mutations, T149S (6.3%) and K189T (42.2%), and one (N) or two (NN) asparagine insertion at the codon 142 (4.7 and 6.3%, respectively) were detected in the Plasmodium/Apicomplexa-specific domain. None of the polymorphisms associated with artemisinin resistance in Southeast Asia was detected in the 138 P. falciparum from Dakar.DiscussionThe present data do not suggest widespread artemisinin resistance in Dakar in 2012–2013. Notably, the C580Y, R539T or Y493H substitutions that were associated with in vitro resistance or delayed parasite clearance in Southeast Asia were not observed in Dakar, nor were any of the polymorphisms observed in parasites from Southeast Asia, nor the M476I mutation that was selected in vitro with artemisinin pressure in a African parasite line.

【 授权许可】

Unknown   
© Torrentino-Madamet et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.