Simple jQuery Dropdowns
Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/46020
Title: A novel field-based molecular assay to detect validated artemisinin-resistant k13 mutants
Authors: Laurence Vachot-Ganée
Nimol Khim
Alexandra Iannello
Eric Legrand
Saorin Kim
Rotha Eam
Chanra Khean
Malen Ken
Elizabeth Ashley
Kyaw Myo Tun
Mehul Dhorda
François Nosten
Issa Mahamat Souleymane
Sophie Blein
Alexandre Pachot
Frédéric Ariey
Karine Kaiser
Didier Ménard
Universite Paris Descartes
BioMérieux SA
Hopital Cochin AP-HP
Mahidol University
Nuffield Department of Clinical Medicine
Institut Pasteur, Paris
Programme National de Lutte Contre le Paludisme au Tchad
Asia Regional Centre
Defence Services Medical Academy
Myanmar Oxford Clinical Research Unit
Pasteur Institute in Cambodia
Keywords: Immunology and Microbiology;Medicine
Issue Date: 24-Apr-2018
Citation: Malaria Journal. Vol.17, No.1 (2018)
Abstract: © 2018 The Author(s). Background: Given the risk of artemisinin resistance spreading from the Greater Mekong sub-region, prospective monitoring in sub-Saharan Africa should be expedited. Molecular biology techniques used for monitoring rely on the detection of k13 validated mutants by using PCR and Sanger sequencing approach, usually not available in malaria endemic areas. Methods: A semi-automated workflow based on the easyMAG® platform and the Argene Solution® (bioMérieux, Marcy l'Etoile, France) as a field-based surveillance tool operable at national level was developed in four steps. Clinical and analytical performances of this tool detecting five of the most frequent and validated k13 mutants (Y493H, I543T, R539T, F446I and C580Y) from dried blood spots (DBS) were compared to the gold standard approach (PCR and Sanger sequencing). Results: By using the ARMS (amplification-refractory mutation system) strategy, the best multiplexing options were found in 3 separate real-time PCR duplexes (IC as internal control/I543T, C580Y/Y493H and F446I/R539T) with limits of detection ranging from 50 (C580Y) to 6.25 parasites/μL (Y493H). In field conditions, using 642 clinical DBS (from symptomatic patients and asymptomatic individuals) collected from Cambodia, Myanmar and Africa (Chad), the overall sensitivity and specificity of the K13 bMx prototype assay developed by bioMérieux were ≥ 90%. Areas under the ROC curves were estimated to be > 0.90 for all k13 mutants in samples from symptomatic patients. Conclusion: The K13 ready-to-use bMx prototype assay, considered by the end-users as a user-friendly assay to perform (in shorter time than the K13 reference assay) and easy to interpret, was found to require less budget planning and had fewer logistical constraints. Its excellent performance qualifies the prototype as a reliable screening tool usable in malaria endemic countries recognized to be at risk of emergence or spread of validated k13 mutants. Additional multi-site studies are needed to evaluate the performances of the K13 bMx prototype assay in different epidemiological contexts such as Africa, India, or South America.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85045882777&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/46020
ISSN: 14752875
Appears in Collections:Scopus 2018

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.