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K13 Propeller Mutations in Plasmodium falciparum Populations in Regions of Malaria Endemicity in Vietnam from 2009 to 2016
The spread of artemisinin-resistant Plasmodium falciparum compromises the therapeutic efficacy of artemisinin combination therapies (ACTs) and is considered the greatest threat to current global initiatives to control and eliminate malaria. This is particularly relevant in Vietnam, where dihydroarte...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5365681/ https://www.ncbi.nlm.nih.gov/pubmed/28137815 http://dx.doi.org/10.1128/AAC.01578-16 |
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author | Thuy-Nhien, Nguyen Tuyen, Nguyen Kim Tong, Nguyen Thanh Vy, Nguyen Tuong Thanh, Ngo Viet Van, Huynh Thuy Huong-Thu, Pham Quang, Huynh Hong Boni, Maciej F. Dolecek, Christiane Farrar, Jeremy Thwaites, Guy E. Miotto, Olivo White, Nicholas J. Hien, Tran Tinh |
author_facet | Thuy-Nhien, Nguyen Tuyen, Nguyen Kim Tong, Nguyen Thanh Vy, Nguyen Tuong Thanh, Ngo Viet Van, Huynh Thuy Huong-Thu, Pham Quang, Huynh Hong Boni, Maciej F. Dolecek, Christiane Farrar, Jeremy Thwaites, Guy E. Miotto, Olivo White, Nicholas J. Hien, Tran Tinh |
author_sort | Thuy-Nhien, Nguyen |
collection | PubMed |
description | The spread of artemisinin-resistant Plasmodium falciparum compromises the therapeutic efficacy of artemisinin combination therapies (ACTs) and is considered the greatest threat to current global initiatives to control and eliminate malaria. This is particularly relevant in Vietnam, where dihydroartemisinin-piperaquine (DP) is the recommended ACT for P. falciparum infection. The propeller domain gene of K13, a molecular marker of artemisinin resistance, was successfully sequenced in 1,060 P. falciparum isolates collected at 3 malaria hot spots in Vietnam between 2009 and 2016. Eight K13 propeller mutations (Thr474Ile, Tyr493His, Arg539Thr, Ile543Thr, Pro553Leu, Val568Gly, Pro574Leu, and Cys580Tyr), including several that have been validated to be artemisinin resistance markers, were found. The prevalences of K13 mutations were 29% (222/767), 6% (11/188), and 43% (45/105) in the Binh Phuoc, Ninh Thuan, and Gia Lai Provinces of Vietnam, respectively. Cys580Tyr became the dominant genotype in recent years, with 79.1% (34/43) of isolates in Binh Phuoc Province and 63% (17/27) of isolates in Gia Lai Province carrying this mutation. K13 mutations were associated with reduced ring-stage susceptibility to dihydroartemisinin (DHA) in vitro and prolonged parasite clearance in vivo. An analysis of haplotypes flanking K13 suggested the presence of multiple strains with the Cys580Tyr mutation rather than a single strain expanding across the three sites. |
format | Online Article Text |
id | pubmed-5365681 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-53656812017-04-12 K13 Propeller Mutations in Plasmodium falciparum Populations in Regions of Malaria Endemicity in Vietnam from 2009 to 2016 Thuy-Nhien, Nguyen Tuyen, Nguyen Kim Tong, Nguyen Thanh Vy, Nguyen Tuong Thanh, Ngo Viet Van, Huynh Thuy Huong-Thu, Pham Quang, Huynh Hong Boni, Maciej F. Dolecek, Christiane Farrar, Jeremy Thwaites, Guy E. Miotto, Olivo White, Nicholas J. Hien, Tran Tinh Antimicrob Agents Chemother Epidemiology and Surveillance The spread of artemisinin-resistant Plasmodium falciparum compromises the therapeutic efficacy of artemisinin combination therapies (ACTs) and is considered the greatest threat to current global initiatives to control and eliminate malaria. This is particularly relevant in Vietnam, where dihydroartemisinin-piperaquine (DP) is the recommended ACT for P. falciparum infection. The propeller domain gene of K13, a molecular marker of artemisinin resistance, was successfully sequenced in 1,060 P. falciparum isolates collected at 3 malaria hot spots in Vietnam between 2009 and 2016. Eight K13 propeller mutations (Thr474Ile, Tyr493His, Arg539Thr, Ile543Thr, Pro553Leu, Val568Gly, Pro574Leu, and Cys580Tyr), including several that have been validated to be artemisinin resistance markers, were found. The prevalences of K13 mutations were 29% (222/767), 6% (11/188), and 43% (45/105) in the Binh Phuoc, Ninh Thuan, and Gia Lai Provinces of Vietnam, respectively. Cys580Tyr became the dominant genotype in recent years, with 79.1% (34/43) of isolates in Binh Phuoc Province and 63% (17/27) of isolates in Gia Lai Province carrying this mutation. K13 mutations were associated with reduced ring-stage susceptibility to dihydroartemisinin (DHA) in vitro and prolonged parasite clearance in vivo. An analysis of haplotypes flanking K13 suggested the presence of multiple strains with the Cys580Tyr mutation rather than a single strain expanding across the three sites. American Society for Microbiology 2017-03-24 /pmc/articles/PMC5365681/ /pubmed/28137815 http://dx.doi.org/10.1128/AAC.01578-16 Text en Copyright © 2017 Thuy-Nhien et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Epidemiology and Surveillance Thuy-Nhien, Nguyen Tuyen, Nguyen Kim Tong, Nguyen Thanh Vy, Nguyen Tuong Thanh, Ngo Viet Van, Huynh Thuy Huong-Thu, Pham Quang, Huynh Hong Boni, Maciej F. Dolecek, Christiane Farrar, Jeremy Thwaites, Guy E. Miotto, Olivo White, Nicholas J. Hien, Tran Tinh K13 Propeller Mutations in Plasmodium falciparum Populations in Regions of Malaria Endemicity in Vietnam from 2009 to 2016 |
title | K13 Propeller Mutations in Plasmodium falciparum Populations in Regions of Malaria Endemicity in Vietnam from 2009 to 2016 |
title_full | K13 Propeller Mutations in Plasmodium falciparum Populations in Regions of Malaria Endemicity in Vietnam from 2009 to 2016 |
title_fullStr | K13 Propeller Mutations in Plasmodium falciparum Populations in Regions of Malaria Endemicity in Vietnam from 2009 to 2016 |
title_full_unstemmed | K13 Propeller Mutations in Plasmodium falciparum Populations in Regions of Malaria Endemicity in Vietnam from 2009 to 2016 |
title_short | K13 Propeller Mutations in Plasmodium falciparum Populations in Regions of Malaria Endemicity in Vietnam from 2009 to 2016 |
title_sort | k13 propeller mutations in plasmodium falciparum populations in regions of malaria endemicity in vietnam from 2009 to 2016 |
topic | Epidemiology and Surveillance |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5365681/ https://www.ncbi.nlm.nih.gov/pubmed/28137815 http://dx.doi.org/10.1128/AAC.01578-16 |
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