Changes in the treatment responses to artesunate-mefloquine on the northwestern border of Thailand during 13 years of continuous deployment.
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 fir...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Public Library of Science
2009
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| _version_ | 1797096945413521408 |
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| author | Carrara, V Zwang, J Ashley, E Price, R Stepniewska, K Barends, M Brockman, A Anderson, T McGready, R Phaiphun, L Proux, S van Vugt, M Hutagalung, R Lwin, K Phyo, A Preechapornkul, P Imwong, M Pukrittayakamee, S Singhasivanon, P White, N Nosten, F |
| author_facet | Carrara, V Zwang, J Ashley, E Price, R Stepniewska, K Barends, M Brockman, A Anderson, T McGready, R Phaiphun, L Proux, S van Vugt, M Hutagalung, R Lwin, K Phyo, A Preechapornkul, P Imwong, M Pukrittayakamee, S Singhasivanon, P White, N Nosten, F |
| author_sort | Carrara, V |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T04:48:43Z |
| format | Journal article |
| id | oxford-uuid:d437c0dc-8dbc-4b6c-8fcb-8e13bbcdf0e1 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:48:43Z |
| publishDate | 2009 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:d437c0dc-8dbc-4b6c-8fcb-8e13bbcdf0e12022-03-27T08:16:49ZChanges in the treatment responses to artesunate-mefloquine on the northwestern border of Thailand during 13 years of continuous deployment.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d437c0dc-8dbc-4b6c-8fcb-8e13bbcdf0e1EnglishSymplectic Elements at OxfordPublic Library of Science2009Carrara, VZwang, JAshley, EPrice, RStepniewska, KBarends, MBrockman, AAnderson, TMcGready, RPhaiphun, LProux, Svan Vugt, MHutagalung, RLwin, KPhyo, APreechapornkul, PImwong, MPukrittayakamee, SSinghasivanon, PWhite, NNosten, F 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. |
| spellingShingle | Carrara, V Zwang, J Ashley, E Price, R Stepniewska, K Barends, M Brockman, A Anderson, T McGready, R Phaiphun, L Proux, S van Vugt, M Hutagalung, R Lwin, K Phyo, A Preechapornkul, P Imwong, M Pukrittayakamee, S Singhasivanon, P White, N Nosten, F Changes in the treatment responses to artesunate-mefloquine on the northwestern border of Thailand during 13 years of continuous deployment. |
| title | Changes in the treatment responses to artesunate-mefloquine on the northwestern border of Thailand during 13 years of continuous deployment. |
| title_full | Changes in the treatment responses to artesunate-mefloquine on the northwestern border of Thailand during 13 years of continuous deployment. |
| title_fullStr | Changes in the treatment responses to artesunate-mefloquine on the northwestern border of Thailand during 13 years of continuous deployment. |
| title_full_unstemmed | Changes in the treatment responses to artesunate-mefloquine on the northwestern border of Thailand during 13 years of continuous deployment. |
| title_short | Changes in the treatment responses to artesunate-mefloquine on the northwestern border of Thailand during 13 years of continuous deployment. |
| title_sort | changes in the treatment responses to artesunate mefloquine on the northwestern border of thailand during 13 years of continuous deployment |
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