Genomic analysis reveals a common breakpoint in amplifications of the Plasmodium vivax multidrug resistance 1 locus in Thailand

In co-endemic regions where mefloquine is used to treat Plasmodium falciparum, drug pressure may select for mefloquine-resistant P. vivax mediated by increased copy number of the multidrug resistance 1 gene (pvmdr1). 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 Kb region with identical breakpoints. A novel breakpoint-specific PCR 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 decline in prevalence after 2012 corresponding with local discontinuation of mefloquine regimens. Assessment of the structure of pvmdr1 amplification in other geographic regions will inform on the population-specificity of the breakpoints and underlying amplification mechanisms.