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Genomic Analysis Reveals a Common Breakpoint in Amplifications of the Plasmodium vivax Multidrug Resistance 1 Locus in Thailand.
- Source :
-
The Journal of infectious diseases [J Infect Dis] 2016 Oct 15; Vol. 214 (8), pp. 1235-42. Date of Electronic Publication: 2016 Jul 24. - Publication Year :
- 2016
-
Abstract
- 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.<br /> (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.)
- Subjects :
- Antimalarials pharmacology
DNA, Protozoan genetics
Gene Dosage genetics
Genomics methods
Genotype
Humans
Malaria, Falciparum drug therapy
Malaria, Falciparum parasitology
Malaria, Vivax drug therapy
Malaria, Vivax parasitology
Mefloquine pharmacology
Membrane Transport Proteins genetics
Plasmodium falciparum drug effects
Plasmodium falciparum genetics
Plasmodium vivax drug effects
Thailand
Drug Resistance, Multiple genetics
Multidrug Resistance-Associated Proteins genetics
Plasmodium vivax genetics
Protozoan Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1537-6613
- Volume :
- 214
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- The Journal of infectious diseases
- Publication Type :
- Academic Journal
- Accession number :
- 27456706
- Full Text :
- https://doi.org/10.1093/infdis/jiw323