title: Spread of artemisinin-resistant Plasmodium falciparum in Myanmar: a cross-sectional survey of the K13 molecular marker.
abstract: BACKGROUND
  Emergence of artemisinin resistance in southeast Asia poses a serious threat to the global control of Plasmodium falciparum malaria. Discovery of the K13 marker has transformed approaches to the monitoring of artemisinin resistance, allowing introduction of molecular surveillance in remote areas through analysis of DNA. We aimed to assess the spread of artemisinin-resistant P falciparum in Myanmar by determining the relative prevalence of P falciparum parasites carrying K13-propeller mutations.
  
  
  METHODS
  We did this cross-sectional survey at malaria treatment centres at 55 sites in ten administrative regions in Myanmar, and in relevant border regions in Thailand and Bangladesh, between January, 2013, and September, 2014. K13 sequences from P falciparum infections were obtained mainly by passive case detection. We entered data into two geostatistical models to produce predictive maps of the estimated prevalence of mutations of the K13 propeller region across Myanmar.
  
  
  RESULTS
  Overall, 371 (39%) of 940 samples carried a K13-propeller mutation. We recorded 26 different mutations, including nine mutations not described previously in southeast Asia. In seven (70%) of the ten administrative regions of Myanmar, the combined K13-mutation prevalence was more than 20%. Geospatial mapping showed that the overall prevalence of K13 mutations exceeded 10% in much of the east and north of the country. In Homalin, Sagaing Region, 25 km from the Indian border, 21 (47%) of 45 parasite samples carried K13-propeller mutations.
  
  
  CONCLUSIONS
  Artemisinin resistance extends across much of Myanmar. We recorded P falciparum parasites carrying K13-propeller mutations at high prevalence next to the northwestern border with India. Appropriate therapeutic regimens should be tested urgently and implemented comprehensively if spread of artemisinin resistance to other regions is to be avoided.
  
  
  BACKGROUND
  Wellcome Trust-Mahidol University-Oxford Tropical Medicine Research Programme and the Bill & Melinda Gates Foundation.
authors.affiliation: Myanmar Oxford Clinical Research Unit, Yangon, Myanmar; Defence Services Medical Research Centre, Naypyitaw, Myanmar.
authors.forename: Kyaw M
authors.initials: KM
authors.lastname: Tun
authors.affiliation: Department of Molecular Tropical Medicine and Genetics, Mahidol University, Bangkok, Thailand; Mahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand. Electronic address: noi@tropmedres.ac.
authors.forename: Mallika
authors.initials: M
authors.lastname: Imwong
authors.affiliation: Shoklo Malaria Research Unit, Mae Sot, Thailand.
authors.forename: Khin M
authors.initials: KM
authors.lastname: Lwin
authors.affiliation: Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Institute of Medicine 1, Yangon, Myanmar.
authors.forename: Aye A
authors.initials: AA
authors.lastname: Win
authors.affiliation: Defence Services Medical Research Centre, Naypyitaw, Myanmar.
authors.forename: Tin M
authors.initials: TM
authors.lastname: Hlaing
authors.affiliation: Defence Services Medical Research Centre, Naypyitaw, Myanmar; Department of Health, Ministry of Health, Naypyitaw, Myanmar.
authors.forename: Thaung
authors.initials: T
authors.lastname: Hlaing
authors.affiliation: Department of Medical Research, Upper Myanmar, Myanmar.
authors.forename: Khin
authors.initials: K
authors.lastname: Lin
authors.affiliation: Department of Medical Research, Lower Myanmar, Myanmar.
authors.forename: Myat P
authors.initials: MP
authors.lastname: Kyaw
authors.affiliation: Mahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Katherine
authors.initials: K
authors.lastname: Plewes
authors.affiliation: Mahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand; Dev Care Foundation, Dhaka, Bangladesh.
authors.forename: M Abul
authors.initials: MA
authors.lastname: Faiz
authors.affiliation: WorldWide Antimalarial Resistance Network, Oxford, UK; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Mehul
authors.initials: M
authors.lastname: Dhorda
authors.affiliation: Mahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Phaik Yeong
authors.initials: PY
authors.lastname: Cheah
authors.affiliation: Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Sasithon
authors.initials: S
authors.lastname: Pukrittayakamee
authors.affiliation: Mahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Ashley
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Tim J C
authors.initials: TJ
authors.lastname: Anderson
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Shalini
authors.initials: S
authors.lastname: Nair
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: McDew-White
authors.affiliation: WorldWide Antimalarial Resistance Network, Oxford, UK; School of Mathematical Sciences, Monash University, Melbourne, Australia.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Flegg
authors.affiliation: WorldWide Antimalarial Resistance Network, Oxford, UK.
authors.forename: Eric P M
authors.initials: EP
authors.lastname: Grist
authors.affiliation: WorldWide Antimalarial Resistance Network, Oxford, UK.
authors.forename: Philippe
authors.initials: P
authors.lastname: Guerin
authors.affiliation: Mahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Maude
authors.affiliation: Myanmar Oxford Clinical Research Unit, Yangon, Myanmar; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Medical Action Myanmar, Yangon, Myanmar.
authors.forename: Frank
authors.initials: F
authors.lastname: Smithuis
authors.affiliation: Mahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Arjen M
authors.initials: AM
authors.lastname: Dondorp
authors.affiliation: Mahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Nicholas P J
authors.initials: NP
authors.lastname: Day
authors.affiliation: Shoklo Malaria Research Unit, Mae Sot, Thailand; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: François
authors.initials: F
authors.lastname: Nosten
authors.affiliation: Mahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.affiliation: Mahidol Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Woodrow
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D001459:Bangladesh / Q000453:epidemiology; D003430:Cross-Sectional Studies; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D004351:Drug Resistance; D005819:Genetic Markers; D005838:Genotype; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000469:parasitology*; D009154:Mutation; D002052:Myanmar / Q000453:epidemiology; D058974:Phylogeography; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics*; D015995:Prevalence; D017422:Sequence Analysis, DNA; D013785:Thailand / Q000453:epidemiology
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D016054:DNA, Protozoan; D005819:Genetic Markers; C031327:artemisinin