title: Changes in the treatment responses to artesunate-mefloquine on the northwestern border of Thailand during 13 years of continuous deployment.
abstract: BACKGROUND
  Artemisinin combination treatments (ACT) are recommended as first line treatment for falciparum malaria throughout the malaria affected world. We reviewed the efficacy of a 3-day regimen of mefloquine and artesunate regimen (MAS(3)), over a 13 year period of continuous deployment as first-line treatment in camps for displaced persons and in clinics for migrant population along the Thai-Myanmar border.
  
  
  RESULTS
  3,264 patients were enrolled in prospective treatment trials between 1995 and 2007 and treated with MAS(3). The proportion of patients with parasitaemia persisting on day-2 increased significantly from 4.5% before 2001 to 21.9% since 2002 (p<0.001). Delayed parasite clearance was associated with increased risk of developing gametocytaemia (AOR = 2.29; 95% CI, 2.00-2.69, p = 0.002). Gametocytaemia on admission and carriage also increased over the years (p = 0.001, test for trend, for both). MAS(3) efficacy has declined slightly but significantly (Hazards ratio 1.13; 95% CI, 1.07-1.19, p<0.001), although efficacy in 2007 remained well within acceptable limits: 96.5% (95% CI, 91.0-98.7). The in vitro susceptibility of P. falciparum to artesunate increased significantly until 2002, but thereafter declined to levels close to those of 13 years ago (geometric mean in 2007: 4.2 nM/l; 95% CI, 3.2-5.5). The proportion of infections caused by parasites with increased pfmdr1 copy number rose from 30% (12/40) in 1996 to 53% (24/45) in 2006 (p = 0.012, test for trend).
  
  
  CONCLUSIONS
  Artesunate-mefloquine remains a highly efficacious antimalarial treatment in this area despite 13 years of widespread intense deployment, but there is evidence of a modest increase in resistance. Of particular concern is the slowing of parasitological response to artesunate and the associated increase in gametocyte carriage.
authors.affiliation: Shoklo Malaria Research Unit, Tak, Thailand.
authors.forename: Verena Ilona
authors.initials: VI
authors.lastname: Carrara
authors.forename: Julien
authors.initials: J
authors.lastname: Zwang
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Ashley
authors.forename: Ric N
authors.initials: RN
authors.lastname: Price
authors.forename: Kasia
authors.initials: K
authors.lastname: Stepniewska
authors.forename: Marion
authors.initials: M
authors.lastname: Barends
authors.forename: Alan
authors.initials: A
authors.lastname: Brockman
authors.forename: Tim
authors.initials: T
authors.lastname: Anderson
authors.forename: Rose
authors.initials: R
authors.lastname: McGready
authors.forename: Lucy
authors.initials: L
authors.lastname: Phaiphun
authors.forename: Stephane
authors.initials: S
authors.lastname: Proux
authors.forename: Michele
authors.initials: M
authors.lastname: van Vugt
authors.forename: Robert
authors.initials: R
authors.lastname: Hutagalung
authors.forename: Khin Maung
authors.initials: KM
authors.lastname: Lwin
authors.forename: Aung Pyae
authors.initials: AP
authors.lastname: Phyo
authors.forename: Piyanuch
authors.initials: P
authors.lastname: Preechapornkul
authors.forename: Mallika
authors.initials: M
authors.lastname: Imwong
authors.forename: Sasithon
authors.initials: S
authors.lastname: Pukrittayakamee
authors.forename: Pratap
authors.initials: P
authors.lastname: Singhasivanon
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.forename: François
authors.initials: F
authors.lastname: Nosten
mesh_terms: D000293:Adolescent; D000962:Antimalarials / Q000627:therapeutic use; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D002986:Clinical Trials as Topic; D004351:Drug Resistance; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D015767:Mefloquine / Q000627:therapeutic use*; D012189:Retrospective Studies; D013785:Thailand; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate; D015767:Mefloquine