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 the remaining 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.
Highlights
Tuberculosis (TB) in Canada is highest among the Inuit, an Indigenous population with a rate over 300 times that of the non-Indigenous Canadian-born population in 2016 (Inuit Tapiriit Kanatami, 2018)
As the TB epidemic continues among the Canadian Inuit, targeted public health interventions are essential to halt ongoing transmission
Several recent studies, including work by our group (Martin et al, 2018), have shown that M. tuberculosis within-host diversity can be transmitted between individuals (Seraphin et al, 2019; Guthrie et al, 2019)
Summary
Tuberculosis (TB) in Canada is highest among the Inuit, an Indigenous population with a rate over 300 times that of the non-Indigenous Canadian-born population in 2016 (Inuit Tapiriit Kanatami, 2018). Recent studies suggest that incorporation of within-host diversity into genomic analyses may provide greater resolution of transmission than cSNP-based approaches alone (Worby et al, 2017; Martin et al, 2018; Meehan et al, 2019; Seraphin et al, 2019) This may be important for investigation of outbreaks occurring over short time scales and/or in settings such as the Canadian North, where the genetic diversity of circulating strains is especially low. ~10-20 times more than usual) makes it easier to detect genetic differences and determine how tuberculosis spreads This approach, known as ‘deep sequencing’, was used to analyze DNA samples of Mtb collected from about 50 people during an outbreak of tuberculosis in 2011-2012, which had previously undergone standard DNA sequencing. We highlight a potential role for deep sequencing in public health investigations, with implications for TB control in Canada’s North as well as other high-transmission environments
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
