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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.    Methods and Findings  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).    Conclusion  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.

Changes in the Treatment Responses to Artesunate-Mefloquine on the Northwestern Border of Thailand during 13 Years of Continuous Deployment