title: Molecular assessment of artemisinin resistance markers, polymorphisms in the k13 propeller, and a multidrug-resistance gene in the eastern and western border areas of Myanmar.
abstract: BACKGROUND
  As K13 propeller mutations have been recently reported to serve as molecular markers, assessment of K13 propeller polymorphisms in multidrug-resistant gene in isolates from Myanmar, especially the eastern and western border areas, is crucial if we are to understand the spread of artemisinin resistance.
  
  
  METHODS
  A 3-day surveillance study was conducted in the eastern and western border areas in Myanmar, and K13 propeller and Plasmodium falciparum multidrug resistance-associated protein 1 (pfmrp1) mutations were analyzed.
  
  
  RESULTS
  Among the 1761 suspected malaria cases screened, a total of 42 uncomplicated falciparum cases from the eastern border and 49 from the western border were subjected to 3 days of surveillance after artemether-lumefantrine treatment. No parasitemic case showing positivity on day 3 was noted from the western border, but 26.2% (11/42) of cases were positive in the eastern border. Although we found no marked difference in the prevalence of the pfmrp1 mutation in the eastern and western borders (36% vs 31%, respectively), K13 mutations were more frequent in the eastern border area (where the 3-day persistent cases were detected; 48% vs 14%). C580Y, M476I, A481V, N458Y, R539T, and R516Y accounted for 68.9% of all K13 mutations significantly associated with day 3 parasitaemia.
  
  
  CONCLUSIONS
  The K13 mutations were significantly associated with day 3 parasitaemia, emphasizing the importance of K13 surveillance. The low prevalence of K13 mutations and the absence of day 3 parasitaemic cases indicate that artemisinin resistance may not have spread to the western Myanmar border region. Although analysis of multiple K13 mutations is challenging, it should be done at various sentinel sites in Myanmar.
authors.affiliation: Department of Medical Research (Lower Myanmar), Yangon, Republic of the Union of Myanmar Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea.
authors.forename: Myat Htut
authors.initials: MH
authors.lastname: Nyunt
authors.affiliation: Department of Health, Nay Pyi Taw, Republic of the Union of Myanmar.
authors.forename: Thaung
authors.initials: T
authors.lastname: Hlaing
authors.affiliation: Department of Medical Research (Lower Myanmar), Yangon, Republic of the Union of Myanmar.
authors.forename: Htet Wai
authors.initials: HW
authors.lastname: Oo
authors.affiliation: Department of Medical Research (Lower Myanmar), Yangon, Republic of the Union of Myanmar.
authors.forename: Lu-Lu Kyaw
authors.initials: LL
authors.lastname: Tin-Oo
authors.affiliation: Department of Medical Research (Lower Myanmar), Yangon, Republic of the Union of Myanmar.
authors.forename: Hnin Phyu
authors.initials: HP
authors.lastname: Phway
authors.affiliation: Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Medical Research (Lower Myanmar), Yangon, Republic of the Union of Myanmar.
authors.forename: Ni Ni
authors.initials: NN
authors.lastname: Zaw
authors.affiliation: Department of Medical Research (Lower Myanmar), Yangon, Republic of the Union of Myanmar.
authors.forename: Soe Soe
authors.initials: SS
authors.lastname: Han
authors.affiliation: Department of Medical Research (Lower Myanmar), Yangon, Republic of the Union of Myanmar.
authors.forename: Thurein
authors.initials: T
authors.lastname: Tun
authors.affiliation: Department of Medical Research (Lower Myanmar), Yangon, Republic of the Union of Myanmar.
authors.forename: Kyaw Kyaw
authors.initials: KK
authors.lastname: San
authors.affiliation: Department of Medical Research (Lower Myanmar), Yangon, Republic of the Union of Myanmar.
authors.forename: Myat Phone
authors.initials: MP
authors.lastname: Kyaw
authors.affiliation: Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea.
authors.forename: Eun-Taek
authors.initials: ET
authors.lastname: Han
mesh_terms: D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D004351:Drug Resistance; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology*; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D002052:Myanmar; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D016054:DNA, Protozoan; D015800:Protozoan Proteins; C031327:artemisinin
keywords: K13 propeller; Myanmar; Plasmodium falciparum; artemisinin resistance; pfmrp1