title: Longitudinal Pooled Deep Sequencing of the Plasmodium vivax K12 Kelch Gene in Cambodia Reveals a Lack of Selection by Artemisinin.
abstract: The emergence of artemisinin resistance among Plasmodium falciparum in the Greater Mekong subregion threatens malaria control interventions and is associated with multiple unique mutations in K13 (PF3D7_1343700). The aim of this study was to survey Cambodian Plasmodium vivax for mutations in the K13 ortholog (K12, PVX_083080) that might similarly confer artemisinin resistance. Extracted DNA from Cambodian isolates collected between 2009 and 2012 was pooled by province and year and submitted for next-generation sequencing. Single-nucleotide polymorphisms (SNPs) were identified using a pile-up approach that detected minority SNPs. Among the 14 pools, we found six unique SNPs, including three nonsynonymous SNPs, across six codons in K12 However, none of the SNPs were orthologous to artemisinin resistance-conferring mutations in PF3D7_1343700, and nonsynonymous changes did not persist through time within populations. These results suggest a lack of selection in the P. vivax population in Cambodia due to artemisinin drug pressure.
authors: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina.|Doctor of Medicine/Doctor of Philosophy Program, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors: Nicholas F
authors: NF
authors: Brazeau
authors: Program in Bioinformatics and Integrative Biology, University of Massachusetts, Worcester, Massachusetts.|School of Medicine, University of Massachusetts, Worcester, Massachusetts.
authors: Nicholas
authors: N
authors: Hathaway
authors: Doctor of Medicine/Doctor of Philosophy Program, University of North Carolina School of Medicine, Chapel Hill, North Carolina.|Curriculum in Genetics and Molecular Biology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors: Christian M
authors: CM
authors: Parobek
authors: Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors: Jessica T
authors: JT
authors: Lin
authors: Program in Bioinformatics and Integrative Biology, University of Massachusetts, Worcester, Massachusetts.|School of Medicine, University of Massachusetts, Worcester, Massachusetts.
authors: Jeffrey A
authors: JA
authors: Bailey
authors: Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors: Chanthap
authors: C
authors: Lon
authors: Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors: David L
authors: DL
authors: Saunders
authors: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina. jjuliano@med.unc.edu.|Program in Bioinformatics and Integrative Biology, University of Massachusetts, Worcester, Massachusetts.|Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors: Jonathan J
authors: JJ
authors: Juliano
mesh_terms: D000962:Antimalarials / Q000627:therapeutic use; D037621:Artemisinins / Q000627:therapeutic use*; D002160:Cambodia / Q000453:epidemiology; D004351:Drug Resistance; D005819:Genetic Markers; D006801:Humans; D016780:Malaria, Vivax / Q000188:drug therapy / Q000453:epidemiology* / Q000469:parasitology*; D021141:Nucleic Acid Amplification Techniques; D010966:Plasmodium vivax / Q000187:drug effects* / Q000235:genetics*; D012641:Selection, Genetic
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D005819:Genetic Markers; C031327:artemisinin