TY - JOUR
T1 - Genomic Analysis Reveals a Common Breakpoint in Amplifications of the Plasmodium vivax Multidrug Resistance 1 Locus in Thailand
AU - Auburn, Sarah
AU - Serre, David
AU - Pearson, Richard D
AU - Amato, R
AU - Sriprawat, K
AU - To, Sheren
AU - Handayuni, Irene
AU - Suwanarusk, Rossarin
AU - Russell, Bruce
AU - Drury, Eleanor
AU - Stalker, Jim
AU - Miotto, Olivo
AU - Kwiatkowski, Dominic
AU - Nosten, François
AU - Price, Ric
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84990941264&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiw323
DO - 10.1093/infdis/jiw323
M3 - Article
C2 - 27456706
VL - 214
SP - 1235
EP - 1242
JO - The Journal of Infectious Diseases
JF - The Journal of Infectious Diseases
SN - 0022-1899
IS - 8
ER -