Analysis of anti-malarial resistance markers in pfmdr1 and pfcrt across Southeast Asia in the Tracking Resistance to Artemisinin Collaboration
Abstract Background Declining anti-malarial efficacy of artemisinin-based combination therapy, and reduced Plasmodium falciparum susceptibility to individual anti-malarials are being documented across an expanding area of Southeast Asia (SEA). Genotypic markers complement phenotypic studies in asses...
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ftdoajarticles:oai:doaj.org/article:e1b4ee86f46e4207a0497d032b7508b4 2023-05-15T15:13:34+02:00 Analysis of anti-malarial resistance markers in pfmdr1 and pfcrt across Southeast Asia in the Tracking Resistance to Artemisinin Collaboration Krongkan Srimuang Olivo Miotto Pharath Lim Rick M. Fairhurst Dominic P. Kwiatkowski Charles J. Woodrow Mallika Imwong for the Tracking Resistance to Artemisinin Collaboration 2016-11-01T00:00:00Z https://doi.org/10.1186/s12936-016-1598-6 https://doaj.org/article/e1b4ee86f46e4207a0497d032b7508b4 EN eng BMC http://link.springer.com/article/10.1186/s12936-016-1598-6 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-016-1598-6 1475-2875 https://doaj.org/article/e1b4ee86f46e4207a0497d032b7508b4 Malaria Journal, Vol 15, Iss 1, Pp 1-12 (2016) Malaria Plasmodium falciparum Anti-malarial resistance Chloroquine Amodiaquine Mefloquine Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2016 ftdoajarticles https://doi.org/10.1186/s12936-016-1598-6 2022-12-31T12:11:21Z Abstract Background Declining anti-malarial efficacy of artemisinin-based combination therapy, and reduced Plasmodium falciparum susceptibility to individual anti-malarials are being documented across an expanding area of Southeast Asia (SEA). Genotypic markers complement phenotypic studies in assessing the efficacy of individual anti-malarials. Methods The markers pfmdr1 and pfcrt were genotyped in parasite samples obtained in 2011–2014 at 14 TRAC (Tracking Resistance to Artemisinin Collaboration) sites in mainland Southeast Asia using a combination of PCR and next-generation sequencing methods. Results Pfmdr1 amplification, a marker of mefloquine and lumefantrine resistance, was highly prevalent at Mae Sot on the Thailand–Myanmar border (59.8% of isolates) and common (more than 10%) at sites in central Myanmar, eastern Thailand and western Cambodia; however, its prevalence was lower than previously documented in Pailin, western Cambodia. The pfmdr1 Y184F mutation was common, particularly in and around Cambodia, and the F1226Y mutation was found in about half of samples in Mae Sot. The functional significance of these two mutations remains unclear. Other previously documented pfmdr1 mutations were absent or very rare in the region. The pfcrt mutation K76T associated with chloroquine resistance was found in 98.2% of isolates. The CVIET haplotype made up 95% or more of isolates in western SEA while the CVIDT haplotype was common (30–40% of isolates) in north and northeastern Cambodia, southern Laos, and southern Vietnam. Conclusions These findings generate cause for concern regarding the mid-term efficacy of artemether–lumefantrine in Myanmar, while the absence of resistance-conferring pfmdr1 mutations and SVMNT pfcrt haplotypes suggests that amodiaquine could be an efficacious component of anti-malarial regimens in SEA. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 15 1 |
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Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Malaria Plasmodium falciparum Anti-malarial resistance Chloroquine Amodiaquine Mefloquine Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Malaria Plasmodium falciparum Anti-malarial resistance Chloroquine Amodiaquine Mefloquine Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Krongkan Srimuang Olivo Miotto Pharath Lim Rick M. Fairhurst Dominic P. Kwiatkowski Charles J. Woodrow Mallika Imwong for the Tracking Resistance to Artemisinin Collaboration Analysis of anti-malarial resistance markers in pfmdr1 and pfcrt across Southeast Asia in the Tracking Resistance to Artemisinin Collaboration |
topic_facet |
Malaria Plasmodium falciparum Anti-malarial resistance Chloroquine Amodiaquine Mefloquine Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Declining anti-malarial efficacy of artemisinin-based combination therapy, and reduced Plasmodium falciparum susceptibility to individual anti-malarials are being documented across an expanding area of Southeast Asia (SEA). Genotypic markers complement phenotypic studies in assessing the efficacy of individual anti-malarials. Methods The markers pfmdr1 and pfcrt were genotyped in parasite samples obtained in 2011–2014 at 14 TRAC (Tracking Resistance to Artemisinin Collaboration) sites in mainland Southeast Asia using a combination of PCR and next-generation sequencing methods. Results Pfmdr1 amplification, a marker of mefloquine and lumefantrine resistance, was highly prevalent at Mae Sot on the Thailand–Myanmar border (59.8% of isolates) and common (more than 10%) at sites in central Myanmar, eastern Thailand and western Cambodia; however, its prevalence was lower than previously documented in Pailin, western Cambodia. The pfmdr1 Y184F mutation was common, particularly in and around Cambodia, and the F1226Y mutation was found in about half of samples in Mae Sot. The functional significance of these two mutations remains unclear. Other previously documented pfmdr1 mutations were absent or very rare in the region. The pfcrt mutation K76T associated with chloroquine resistance was found in 98.2% of isolates. The CVIET haplotype made up 95% or more of isolates in western SEA while the CVIDT haplotype was common (30–40% of isolates) in north and northeastern Cambodia, southern Laos, and southern Vietnam. Conclusions These findings generate cause for concern regarding the mid-term efficacy of artemether–lumefantrine in Myanmar, while the absence of resistance-conferring pfmdr1 mutations and SVMNT pfcrt haplotypes suggests that amodiaquine could be an efficacious component of anti-malarial regimens in SEA. |
format |
Article in Journal/Newspaper |
author |
Krongkan Srimuang Olivo Miotto Pharath Lim Rick M. Fairhurst Dominic P. Kwiatkowski Charles J. Woodrow Mallika Imwong for the Tracking Resistance to Artemisinin Collaboration |
author_facet |
Krongkan Srimuang Olivo Miotto Pharath Lim Rick M. Fairhurst Dominic P. Kwiatkowski Charles J. Woodrow Mallika Imwong for the Tracking Resistance to Artemisinin Collaboration |
author_sort |
Krongkan Srimuang |
title |
Analysis of anti-malarial resistance markers in pfmdr1 and pfcrt across Southeast Asia in the Tracking Resistance to Artemisinin Collaboration |
title_short |
Analysis of anti-malarial resistance markers in pfmdr1 and pfcrt across Southeast Asia in the Tracking Resistance to Artemisinin Collaboration |
title_full |
Analysis of anti-malarial resistance markers in pfmdr1 and pfcrt across Southeast Asia in the Tracking Resistance to Artemisinin Collaboration |
title_fullStr |
Analysis of anti-malarial resistance markers in pfmdr1 and pfcrt across Southeast Asia in the Tracking Resistance to Artemisinin Collaboration |
title_full_unstemmed |
Analysis of anti-malarial resistance markers in pfmdr1 and pfcrt across Southeast Asia in the Tracking Resistance to Artemisinin Collaboration |
title_sort |
analysis of anti-malarial resistance markers in pfmdr1 and pfcrt across southeast asia in the tracking resistance to artemisinin collaboration |
publisher |
BMC |
publishDate |
2016 |
url |
https://doi.org/10.1186/s12936-016-1598-6 https://doaj.org/article/e1b4ee86f46e4207a0497d032b7508b4 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 15, Iss 1, Pp 1-12 (2016) |
op_relation |
http://link.springer.com/article/10.1186/s12936-016-1598-6 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-016-1598-6 1475-2875 https://doaj.org/article/e1b4ee86f46e4207a0497d032b7508b4 |
op_doi |
https://doi.org/10.1186/s12936-016-1598-6 |
container_title |
Malaria Journal |
container_volume |
15 |
container_issue |
1 |
_version_ |
1766344106241425408 |