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UBC Theses and Dissertations

Unravelling the thread of transmission : pairing traditional epidemiology with genomics to understand tuberculosis transmission dynamics Guthrie, Jennifer L.


Background: In Canada, TB remains a public health concern, with the disease becoming increasingly entrenched in our most vulnerable populations. In 2012, British Columbia (BC) prepared a strategic plan with the aim of reducing incidence in the province by 50% over 10 years. A key aspect of this is preventing person-to-person spread of TB within BC—challenging, as our understanding of endemic transmission is incomplete. The objective of this dissertation is to use new advances in technology, including whole genome sequencing (WGS), to address the knowledge gaps around who, where, and how transmission occurs in BC and provide the foundation upon which new TB prevention policies and programs will be developed. Methods: This dissertation draws on data routinely collected from persons diagnosed with culture-confirmed TB in BC (2005–2014) and linked to laboratory data from their corresponding Mycobacterium tuberculosis (Mtb) isolate(s). Collaborations with Yukon and Ontario provided additional data. 24-locus MIRU-VNTR genotype results were available for each Mtb isolate across all three study populations. WGS of genotypically clustered BC isolates and all Yukon isolates was carried out and the data analyzed using a bioinformatics pipeline developed at Oxford University. Descriptive and inferential statistics were used to examine clinical and demographic characteristics of persons with Mtb isolates belonging to a cluster according to genotyping and WGS methods. Results: Universal genotyping of all Mtb isolates collected in BC over a ten-year period revealed that 57.6% of the study population had a genotypically unique Mtb isolate. Sixteen large genotype clusters were identified, nine in predominately Canadian-born (CB) persons. Application of WGS indicated the large genotypic clusters comprised of mainly non-Canadian-born (nCB) persons did not represent recent, endemic transmission within BC, and WGS additionally refined many of the CB clusters to smaller sub-clusters. The WGS clustered proportion was 25.8%. Conclusions: Approximately one in four of BC’s TB cases occur in CB persons and are largely the result of local transmission. WGS represents a new and important tool for understanding the spread of TB within a population, and using this technology paired with routinely collected case-level data provided significant insights to transmission in BC.

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