Previously undetected super-spreading of Mycobacterium tuberculosis revealed by deep sequencing

Abstract
Data availability
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Abstract

Tuberculosis disproportionately affects the Canadian Inuit. To address this, it is imperative we understand transmission dynamics in this population. We investigate whether 'deep' sequencing can provide additional resolution compared to standard sequencing, using a well-characterized outbreak from the Arctic (2011-2012, 50 cases). Samples were sequenced to ~500-1000x and reads were aligned to a novel local reference genome generated with PacBio SMRT sequencing. Consensus and heterogeneous variants were identified and compared across genomes. In contrast with previous genomic analyses using ~50x depth, deep sequencing allowed us to identify a novel super-spreader who likely transmitted to up to 17 other cases during the outbreak (35% of all cases that year). It is increasingly evident that within-host diversity should be incorporated into transmission analyses; deep sequencing may facilitate more accurate detection of super-spreaders and transmission clusters. This has implications not only for TB, but all genomic studies of transmission - regardless of pathogen.

Data availability

Sequencing data and the assembly for MT-0080 are available on the NCBI's Sequence Read Archive under BioProject PRJNA549270.

The following data sets were generated

1. Lee RS
2. Proulx J-F
3. McIntosh F
4. Behr MA
5. Hanage WP
(2019) Deep sequencing of a major TB outbreak in the Canadian Arctic
NCBI SRA Bioproject, PRJNA549270.

https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA549270

Article and author information

Author details

Robyn S Lee

Epidemiology Division, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada

For correspondence
robyn.s.c.lee@gmail.com

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-7120-9053
Jean-François Proulx

Nunavik Regional Board of Health and Social Services, Kuujjuaq, Canada

Competing interests
The authors declare that no competing interests exist.
Fiona McIntosh

The Research Institute of McGill University Health Centre, Montréal, Canada

Competing interests
The authors declare that no competing interests exist.
Marcel A Behr

The Research Institute of McGill University Health Centre, Montréal, Canada

Competing interests
The authors declare that no competing interests exist.
William P Hanage

Center for Communicable Disease Dynamics, Harvard TH Chan School of Public Health, Boston, United States

Competing interests
The authors declare that no competing interests exist.

Funding

National Institutes of Health (R01AI128344)

William P Hanage

Canadian Institutes of Health Research (Fellowship 152448)

Robyn S Lee

Canadian Institutes of Health Research (Foundation Award 148362)

Marcel A Behr

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: Ethics approval was obtained from the Institutional Review Board (IRB) of the Harvard T.H. Chan School of Public Health (IRB18-0552) and the IRB of McGill University Faculty of Medicine (IRB A02-M08-18A). Clinical and epidemiological data were previously collected as part of the routine public health response and all data was analyzed in non-nominal fashion, using unique identifiers, therefore individual patient consent was not required. This study was done in collaboration with the Nunavik Regional Board of Health and Social Services.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.