Whole genome sequencing for improved understanding of Mycobacterium tuberculosis transmission in a remote circumpolar region.

J L Guthrie,P Tang,L Strudwick,V J Cook,J L Gardy,D Jorgensen,M Allen,M Rodrigues,B Roberts,B Hanley,J Johnston,D Roth,J Mcfadzen

doi:10.1017/s0950268819000670

Abstract

Few studies have used genomic epidemiology to understand tuberculosis (TB) transmission in rural and remote settings - regions often unique in history, geography and demographics. To improve our understanding of TB transmission dynamics in Yukon Territory (YT), a circumpolar Canadian territory, we conducted a retrospective analysis in which we combined epidemiological data collected through routine contact investigations with clinical and laboratory results. Mycobacterium tuberculosis isolates from all culture-confirmed TB cases in YT (2005-2014) were genotyped using 24-locus Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) and compared to each other and to those from the neighbouring province of British Columbia (BC). Whole genome sequencing (WGS) of genotypically clustered isolates revealed three sustained transmission networks within YT, two of which also involved BC isolates. While each network had distinct characteristics, all had at least one individual acting as the probable source of three or more culture-positive cases. Overall, WGS revealed that TB transmission dynamics in YT are distinct from patterns of spread in other, more remote Northern Canadian regions, and that the combination of WGS and epidemiological data can provide actionable information to local public health teams.

Highlights

Canada’s tuberculosis (TB) rate has been decreasing overall, yet rates remain elevated in particular populations and regions
Recognising that in contrast to many other northern regions in Canada, year-round highway access and multiple airports facilitate travel between Yukon Territory (YT) and its southern neighbour, British Columbia (BC), we examined YT Mycobacterium tuberculosis (Mtb) genomes in the context of Mtb genomes sequenced in BC during the same time period
Whole genome sequencing (WGS) was completed for all 32 YT isolates as well as 1284 BC isolates – which included all isolates genotypically clustered by MIRU-VNTR to a YT isolate

Summary

Introduction

Canada’s tuberculosis (TB) rate has been decreasing overall, yet rates remain elevated in particular populations and regions. Recent outbreaks in two areas of Canada’s North – Nunavik and Nunavut – resulted in annual incidence rates higher than many low-income countries [1, 2]. This is not the case in all circumpolar settings, where public health efforts have contributed to declining TB rates. From 2006 through 2012, Yukon Territory (YT) reported a rate of 12.1 cases per 100 000 population While this is over twice the national average of 4.8 cases/100 000, it is the lowest rate amongst Canada’s Northern territories (25.4/100 000 in the Northwest Territories, immediately east of YT, and 194.3/100 000 in Nunavut) [2, 3]. Understanding the unique epidemiology of TB in each region is vital to delivering tailored interventions to drive rates in circumpolar settings closer to the World Health Organization’s elimination goals

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Conclusion