Application of whole genome sequence analysis to the study of Mycobacterium tuberculosis in Nunavut, Canada.

Canada has one of the lowest rates of tuberculosis (TB) in the world, however, among certain sub-populations, disease incidence rates approach those observed in sub-Saharan Africa, and other high incidence regions. In this study, we applied mycobacterial interspersed repetitive unit (MIRU) variable...

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Main Authors: Andrea D Tyler, Elaine Randell, Maureen Baikie, Kym Antonation, Debra Janella, Sara Christianson, Gregory J Tyrrell, Morag Graham, Gary Van Domselaar, Meenu K Sharma
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5628838?pdf=render
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author Andrea D Tyler
Elaine Randell
Maureen Baikie
Kym Antonation
Debra Janella
Sara Christianson
Gregory J Tyrrell
Morag Graham
Gary Van Domselaar
Meenu K Sharma
author_facet Andrea D Tyler
Elaine Randell
Maureen Baikie
Kym Antonation
Debra Janella
Sara Christianson
Gregory J Tyrrell
Morag Graham
Gary Van Domselaar
Meenu K Sharma
author_sort Andrea D Tyler
collection DOAJ
description Canada has one of the lowest rates of tuberculosis (TB) in the world, however, among certain sub-populations, disease incidence rates approach those observed in sub-Saharan Africa, and other high incidence regions. In this study, we applied mycobacterial interspersed repetitive unit (MIRU) variable number of tandem repeat (VNTR) and whole genome sequencing (WGS) to the analysis of Mycobacterium tuberculosis isolates obtained from Northern communities in the territory of Nunavut. WGS was carried out using the Illumina MiSeq, with identified variants used to infer phylogenetic relationships and annotated to infer functional implications. Additionally, the sequencing data from these isolates were augmented with publically available WGS to evaluate data from the Nunavut outbreak in the broader Canadian context. In this study, isolates could be classified into four major clusters by MIRU-VNTR analysis. These could be further resolved into sub-clusters using WGS. No evidence for antimicrobial resistance, either genetic or phenotypic, was observed in this cohort. Among most subjects with multiple samples, reactivation/incomplete treatment likely contributed to recurrence. However, isolates from two subjects appeared more likely to have occurred via reinfection, based on the large number of genomic single nucleotide variants detected. Finally, although quite distinct from previously reported Canadian MTB strains, isolates obtained from Nunavut clustered most closely with a cohort of samples originating in the Nunavik region of Northern Quebec. This study demonstrates the benefit of using WGS for discriminatory analysis of MTB in Canada, especially in high incidence regions. It further emphasizes the importance of focusing epidemiological intervention efforts on interrupting transmission chains of endemic TB throughout Northern communities, rather than relying on strategies applied in regions where the majority of TB cases result from importation of foreign strains.
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spelling doaj.art-86f8301820ad49be9d44d29f8ef7dce52022-12-22T03:06:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-011210e018565610.1371/journal.pone.0185656Application of whole genome sequence analysis to the study of Mycobacterium tuberculosis in Nunavut, Canada.Andrea D TylerElaine RandellMaureen BaikieKym AntonationDebra JanellaSara ChristiansonGregory J TyrrellMorag GrahamGary Van DomselaarMeenu K SharmaCanada has one of the lowest rates of tuberculosis (TB) in the world, however, among certain sub-populations, disease incidence rates approach those observed in sub-Saharan Africa, and other high incidence regions. In this study, we applied mycobacterial interspersed repetitive unit (MIRU) variable number of tandem repeat (VNTR) and whole genome sequencing (WGS) to the analysis of Mycobacterium tuberculosis isolates obtained from Northern communities in the territory of Nunavut. WGS was carried out using the Illumina MiSeq, with identified variants used to infer phylogenetic relationships and annotated to infer functional implications. Additionally, the sequencing data from these isolates were augmented with publically available WGS to evaluate data from the Nunavut outbreak in the broader Canadian context. In this study, isolates could be classified into four major clusters by MIRU-VNTR analysis. These could be further resolved into sub-clusters using WGS. No evidence for antimicrobial resistance, either genetic or phenotypic, was observed in this cohort. Among most subjects with multiple samples, reactivation/incomplete treatment likely contributed to recurrence. However, isolates from two subjects appeared more likely to have occurred via reinfection, based on the large number of genomic single nucleotide variants detected. Finally, although quite distinct from previously reported Canadian MTB strains, isolates obtained from Nunavut clustered most closely with a cohort of samples originating in the Nunavik region of Northern Quebec. This study demonstrates the benefit of using WGS for discriminatory analysis of MTB in Canada, especially in high incidence regions. It further emphasizes the importance of focusing epidemiological intervention efforts on interrupting transmission chains of endemic TB throughout Northern communities, rather than relying on strategies applied in regions where the majority of TB cases result from importation of foreign strains.http://europepmc.org/articles/PMC5628838?pdf=render
spellingShingle Andrea D Tyler
Elaine Randell
Maureen Baikie
Kym Antonation
Debra Janella
Sara Christianson
Gregory J Tyrrell
Morag Graham
Gary Van Domselaar
Meenu K Sharma
Application of whole genome sequence analysis to the study of Mycobacterium tuberculosis in Nunavut, Canada.
PLoS ONE
title Application of whole genome sequence analysis to the study of Mycobacterium tuberculosis in Nunavut, Canada.
title_full Application of whole genome sequence analysis to the study of Mycobacterium tuberculosis in Nunavut, Canada.
title_fullStr Application of whole genome sequence analysis to the study of Mycobacterium tuberculosis in Nunavut, Canada.
title_full_unstemmed Application of whole genome sequence analysis to the study of Mycobacterium tuberculosis in Nunavut, Canada.
title_short Application of whole genome sequence analysis to the study of Mycobacterium tuberculosis in Nunavut, Canada.
title_sort application of whole genome sequence analysis to the study of mycobacterium tuberculosis in nunavut canada
url http://europepmc.org/articles/PMC5628838?pdf=render
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