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Emerging polymorphisms in falciparum Kelch 13 gene in Northeastern region of India

BACKGROUND: Recent reports of emergence and spread of artemisinin resistance in the Southeast Asia region, including Myanmar, pose a greater threat to malaria control and elimination in India. Whole genome sequencing studies have associated mutations in the K13 propeller gene (k13), PF3D7_1343700 wi...

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Autores principales: Mishra, Neelima, Bharti, Ram Suresh, Mallick, Prashant, Singh, Om Prakash, Srivastava, Bina, Rana, Roma, Phookan, Sobhan, Gupta, Hardev Prasad, Ringwald, Pascal, Valecha, Neena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5135801/
https://www.ncbi.nlm.nih.gov/pubmed/27912758
http://dx.doi.org/10.1186/s12936-016-1636-4
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author Mishra, Neelima
Bharti, Ram Suresh
Mallick, Prashant
Singh, Om Prakash
Srivastava, Bina
Rana, Roma
Phookan, Sobhan
Gupta, Hardev Prasad
Ringwald, Pascal
Valecha, Neena
author_facet Mishra, Neelima
Bharti, Ram Suresh
Mallick, Prashant
Singh, Om Prakash
Srivastava, Bina
Rana, Roma
Phookan, Sobhan
Gupta, Hardev Prasad
Ringwald, Pascal
Valecha, Neena
author_sort Mishra, Neelima
collection PubMed
description BACKGROUND: Recent reports of emergence and spread of artemisinin resistance in the Southeast Asia region, including Myanmar, pose a greater threat to malaria control and elimination in India. Whole genome sequencing studies have associated mutations in the K13 propeller gene (k13), PF3D7_1343700 with artemisinin resistance both in vitro and in vivo. The aim of the present study was to find the k13 gene polymorphisms in Plasmodium falciparum parasites from the three sites in the Northeast region of India, bordering Bangladesh and Myanmar. METHODS: A total of 254 samples collected during 2014–2015 from Tripura, Mizoram and Arunachal Pradesh states in the Northeast region of India were used to obtain the full-length k13 gene sequences. RESULTS: Three non-synonymous (NS) mutations: two in the propeller region, namely at codon 446 and 578, were observed besides one at codon 189 in the non-propeller region. The treatment outcome was not affected by these mutations at any of the sites. In addition, microsatellite variation in the N-terminus of the k13 protein was observed at all the study sites. CONCLUSION: This is the first study to document the presence of F446I NS mutation in the k13 propeller region from Changlang district, Arunachal Pradesh, a site adjoining the Indo-Myanmar border region, where this mutation is highly prevalent. In addition, NS mutation A578S has been observed only at Lunglei district, Mizoram, a site bordering Bangladesh and K189T mutation with relatively higher frequency in Mizoram and Tripura states. The presence of F446I mutation in a region close to the Myanmar border is notable. Considering the spread of anti-malarial drug resistance from Southeast Asia to the Northeast region of India in the past, there is an urgent need to undertake systematic mapping studies to ascertain the role and extent of this mutation in artemisinin resistance in this region of country.
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spelling pubmed-51358012016-12-15 Emerging polymorphisms in falciparum Kelch 13 gene in Northeastern region of India Mishra, Neelima Bharti, Ram Suresh Mallick, Prashant Singh, Om Prakash Srivastava, Bina Rana, Roma Phookan, Sobhan Gupta, Hardev Prasad Ringwald, Pascal Valecha, Neena Malar J Research BACKGROUND: Recent reports of emergence and spread of artemisinin resistance in the Southeast Asia region, including Myanmar, pose a greater threat to malaria control and elimination in India. Whole genome sequencing studies have associated mutations in the K13 propeller gene (k13), PF3D7_1343700 with artemisinin resistance both in vitro and in vivo. The aim of the present study was to find the k13 gene polymorphisms in Plasmodium falciparum parasites from the three sites in the Northeast region of India, bordering Bangladesh and Myanmar. METHODS: A total of 254 samples collected during 2014–2015 from Tripura, Mizoram and Arunachal Pradesh states in the Northeast region of India were used to obtain the full-length k13 gene sequences. RESULTS: Three non-synonymous (NS) mutations: two in the propeller region, namely at codon 446 and 578, were observed besides one at codon 189 in the non-propeller region. The treatment outcome was not affected by these mutations at any of the sites. In addition, microsatellite variation in the N-terminus of the k13 protein was observed at all the study sites. CONCLUSION: This is the first study to document the presence of F446I NS mutation in the k13 propeller region from Changlang district, Arunachal Pradesh, a site adjoining the Indo-Myanmar border region, where this mutation is highly prevalent. In addition, NS mutation A578S has been observed only at Lunglei district, Mizoram, a site bordering Bangladesh and K189T mutation with relatively higher frequency in Mizoram and Tripura states. The presence of F446I mutation in a region close to the Myanmar border is notable. Considering the spread of anti-malarial drug resistance from Southeast Asia to the Northeast region of India in the past, there is an urgent need to undertake systematic mapping studies to ascertain the role and extent of this mutation in artemisinin resistance in this region of country. BioMed Central 2016-12-03 /pmc/articles/PMC5135801/ /pubmed/27912758 http://dx.doi.org/10.1186/s12936-016-1636-4 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Mishra, Neelima
Bharti, Ram Suresh
Mallick, Prashant
Singh, Om Prakash
Srivastava, Bina
Rana, Roma
Phookan, Sobhan
Gupta, Hardev Prasad
Ringwald, Pascal
Valecha, Neena
Emerging polymorphisms in falciparum Kelch 13 gene in Northeastern region of India
title Emerging polymorphisms in falciparum Kelch 13 gene in Northeastern region of India
title_full Emerging polymorphisms in falciparum Kelch 13 gene in Northeastern region of India
title_fullStr Emerging polymorphisms in falciparum Kelch 13 gene in Northeastern region of India
title_full_unstemmed Emerging polymorphisms in falciparum Kelch 13 gene in Northeastern region of India
title_short Emerging polymorphisms in falciparum Kelch 13 gene in Northeastern region of India
title_sort emerging polymorphisms in falciparum kelch 13 gene in northeastern region of india
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5135801/
https://www.ncbi.nlm.nih.gov/pubmed/27912758
http://dx.doi.org/10.1186/s12936-016-1636-4
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