Publication: Genomic Analysis Reveals a Common Breakpoint in Amplifications of the Plasmodium vivax Multidrug Resistance 1 Locus in Thailand
Issued Date
2016-10-15
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ISSN
15376613
00221899
00221899
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2-s2.0-84990941264
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Infectious Diseases. Vol.214, No.8 (2016), 1235-1242
Suggested Citation
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 Genomic Analysis Reveals a Common Breakpoint in Amplifications of the Plasmodium vivax Multidrug Resistance 1 Locus in Thailand. Journal of Infectious Diseases. Vol.214, No.8 (2016), 1235-1242. doi:10.1093/infdis/jiw323 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/41097
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Title
Genomic Analysis Reveals a Common Breakpoint in Amplifications of the Plasmodium vivax Multidrug Resistance 1 Locus in Thailand
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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.