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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/41097
Title: Genomic Analysis Reveals a Common Breakpoint in Amplifications of the Plasmodium vivax Multidrug Resistance 1 Locus in Thailand
Authors: Sarah Auburn
David Serre
Richard D. Pearson
Roberto Amato
Kanlaya Sriprawat
Sheren To
Irene Handayuni
Rossarin Suwanarusk
Bruce Russell
Eleanor Drury
Jim Stalker
Olivo Miotto
Dominic P. Kwiatkowski
Francois Nosten
Ric N. Price
Menzies School of Health Research
Cleveland Clinic Foundation
Wellcome Trust Sanger Institute
Wellcome Trust Centre for Human Genetics
Medical Research Council Centre for Genomics and Global Health
University of Oxford
Mahidol University
University of Otago
A-Star, Singapore Immunology Network
Keywords: Medicine
Issue Date: 15-Oct-2016
Citation: Journal of Infectious Diseases. Vol.214, No.8 (2016), 1235-1242
Abstract: © 2016 The Author. In regions of coendemicity for Plasmodium falciparum and Plasmodium vivax where mefloquine is used to treat P. falciparum infection, drug pressure mediated by increased copy numbers of the multidrug resistance 1 gene (pvmdr1) may select for mefloquine-resistant P. vivax. Surveillance is not undertaken routinely owing in part to methodological challenges in detection of gene amplification. Using genomic data on 88 P. vivax samples from western Thailand, we identified pvmdr1 amplification in 17 isolates, all exhibiting tandem copies of a 37.6-kilobase pair region with identical breakpoints. A novel breakpoint-specific polymerase chain reaction assay was designed to detect the amplification. The assay demonstrated high sensitivity, identifying amplifications in 13 additional, polyclonal infections. Application to 132 further samples identified the common breakpoint in all years tested (2003-2015), with a decline in prevalence after 2012 corresponding to local discontinuation of mefloquine regimens. Assessment of the structure of pvmdr1 amplification in other geographic regions will yield information about the population-specificity of the breakpoints and underlying amplification mechanisms.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84990941264&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/41097
ISSN: 15376613
00221899
Appears in Collections:Scopus 2016-2017

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