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

Carrara, Verene I., Zwang, Julien, Ashley, Elizabeth A., Price, Ric N., Stepniewska, Kasia, Barends, Marion, Brockman, Alan, Anderson, Tim, McGready, Rose, Phaiphun, Lucy, Proux, Stephane, van Vugt, Michele, Hutagalung, R., Lwin, Khin M., Phyo, Aung Pyae, Preechapornkul, P., Imwong, Mallika, Pukrittayakamee, Sasithon, Singhasivanon, Pratap, White, Nicholas J. and et al. (2009). Changes in the Treatment Responses to Artesunate-Mefloquine on the Northwestern Border of Thailand during 13 Years of Continuous Deployment. PLoS ONE,4(2):e4551.

Document type: Journal Article
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Title Changes in the Treatment Responses to Artesunate-Mefloquine on the Northwestern Border of Thailand during 13 Years of Continuous Deployment
Author Carrara, Verene I.
Zwang, Julien
Ashley, Elizabeth A.
Price, Ric N.
Stepniewska, Kasia
Barends, Marion
Brockman, Alan
Anderson, Tim
McGready, Rose
Phaiphun, Lucy
Proux, Stephane
van Vugt, Michele
Hutagalung, R.
Lwin, Khin M.
Phyo, Aung Pyae
Preechapornkul, P.
Imwong, Mallika
Pukrittayakamee, Sasithon
Singhasivanon, Pratap
White, Nicholas J.
et al.
Journal Name PLoS ONE
Publication Date 2009
Volume Number 4
Issue Number 2
ISSN 1932-6203   (check CDU catalogue  open catalogue search in new window)
Start Page e4551
Total Pages 11
Place of Publication San Francisco, CA, United States
Publisher Public Library of Science
HERDC Category C1 - Journal Article (DEST)
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 (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 Findings

3,264 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).

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.
Keywords treatment responses
Artesunate-Mefloquine
Thailand
DOI http://dx.doi.org/10.1371/journal.pone.0004551   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)


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