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

Abstract

BackgroundArtemisinin 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 (MAS3), 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 Findings3,264 patients were enrolled in prospective treatment trials between 1995 and 2007 and treated with MAS3. 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). MAS3 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).ConclusionArtesunate-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.

Therapeutic Efficacy and Effects of Artesunate-Mefloquine and Mefloquine Alone on Malaria-Associated Anemia in Children with Uncomplicated Plasmodium falciparum Malaria in Southwest Nigeria

“…32,34,[37][38][39][40][41] However, in certain areas, for example, along Cambodia-Thailand and northwestern border of Thailand, the efficacy of AMQ is declining primarily because of resistance to MQ. 42,43 Recently, artemisinin resistance has been reported in Cambodia. 44 Thus, close monitoring will be needed with the use of AMQ in those areas of West Africa where reduced in vitro susceptibility has been reported to MQ and artemisinin 13 and where patients are more likely to take the artesunate and leave the MQ component or the possibility of providers selling one drug to reduce costs in co-packaging now available in many endemic areas of West Africa.…”

No Evidence of Delayed Parasite Clearance after Oral Artesunate Treatment of Uncomplicated Falciparum Malaria in Mali

“…The two most powerful predictors of parasite clearance time were age (proxy for acquired immunity in this population) and asexual parasitemia at the time of enrollment. [15][16][17][18] Based on previous studies, [16][17][18][19] the following variables were also included in the initial models as potential confounders of parasite clearance: sex, mixed parasite infection, and hemoglobin, gametocyte density, gametocyte carriage, and fever at the time of enrollment. All statistical analyses were done with Stata version 11.0 (StataCorp., College Station, TX).…”

Evolution of Plasmodium falciparum drug resistance: implications for the development and containment of artemisinin resistance

“…An intensive study conducted at a different site in western Cambodia in 2007-08 reported a significant delay in parasite clearance time following treatment with artesunate monotherapy and with ACT (artesunate ＋ mefloquine), as compared with parasite clearance times observed in eastern Thailand (87). Of note, the reduction of therapeutic responses to ACT has not been geographically confined to western Cambodia but also observed in southern Cambodia (88), on the ThailandMyanmar border (89), and in Yunnan in China (90). In particular, the proportion of patients showing a very slow rate of parasite clearance rapidly increased from 0.6z in 2001 to 20z in 2010 on the northwestern border of Thailand (91).…”