title: Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study.
abstract: BACKGROUND
  Artemisinin-resistant falciparum malaria has arisen in western Cambodia. A concerted international effort is underway to contain artemisinin-resistant Plasmodium falciparum, but containment strategies are dependent on whether resistance has emerged elsewhere. We aimed to establish whether artemisinin resistance has spread or emerged on the Thailand-Myanmar (Burma) border.
  
  
  METHODS
  In malaria clinics located along the northwestern border of Thailand, we measured six hourly parasite counts in patients with uncomplicated hyperparasitaemic falciparum malaria (≥4% infected red blood cells) who had been given various oral artesunate-containing regimens since 2001. Parasite clearance half-lives were estimated and parasites were genotyped for 93 single nucleotide polymorphisms.
  
  
  RESULTS
  3202 patients were studied between 2001 and 2010. Parasite clearance half-lives lengthened from a geometric mean of 2·6 h (95% CI 2·5-2·7) in 2001, to 3·7 h (3·6-3·8) in 2010, compared with a mean of 5·5 h (5·2-5·9) in 119 patients in western Cambodia measured between 2007 and 2010. The proportion of slow-clearing infections (half-life ≥6·2 h) increased from 0·6% in 2001, to 20% in 2010, compared with 42% in western Cambodia between 2007 and 2010. Of 1583 infections genotyped, 148 multilocus parasite genotypes were identified, each of which infected between two and 13 patients. The proportion of variation in parasite clearance attributable to parasite genetics increased from 30% between 2001 and 2004, to 66% between 2007 and 2010.
  
  
  CONCLUSIONS
  Genetically determined artemisinin resistance in P falciparum emerged along the Thailand-Myanmar border at least 8 years ago and has since increased substantially. At this rate of increase, resistance will reach rates reported in western Cambodia in 2-6 years.
  
  
  BACKGROUND
  The Wellcome Trust and National Institutes of Health.
authors.affiliation: Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Aung Pyae
authors.initials: AP
authors.lastname: Phyo
authors.forename: Standwell
authors.initials: S
authors.lastname: Nkhoma
authors.forename: Kasia
authors.initials: K
authors.lastname: Stepniewska
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Ashley
authors.forename: Shalini
authors.initials: S
authors.lastname: Nair
authors.forename: Rose
authors.initials: R
authors.lastname: McGready
authors.forename: Carit
authors.initials: C
authors.lastname: ler Moo
authors.forename: Salma
authors.initials: S
authors.lastname: Al-Saai
authors.forename: Arjen M
authors.initials: AM
authors.lastname: Dondorp
authors.forename: Khin Maung
authors.initials: KM
authors.lastname: Lwin
authors.forename: Pratap
authors.initials: P
authors.lastname: Singhasivanon
authors.forename: Nicholas P J
authors.initials: NP
authors.lastname: Day
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.forename: Tim J C
authors.initials: TJ
authors.lastname: Anderson
authors.forename: François
authors.initials: F
authors.lastname: Nosten
mesh_terms: D000962:Antimalarials / Q000008:administration & dosage; D037621:Artemisinins / Q000008:administration & dosage; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control; D008297:Male; D010270:Parasite Egg Count; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013785:Thailand / Q000453:epidemiology
chemical_list: D000962:Antimalarials; D037621:Artemisinins