The public health utility of whole genome sequencing: Insights from a tuberculosis outbreak in Australia and perspectives of public health professionals.

Abstract

Whole Genome Sequencing (WGS) is increasingly being used to enhance tuberculosis (TB) surveillance and management. However, evidence on how WGS shapes real-world decision-making remains limited. This study explored the utility of WGS in the context of a TB outbreak in Victoria, Australia. We conducted a case study to (1) describe a TB outbreak in Victoria using epidemiological and genomic data and (2) explore the perceived benefits and limitations of WGS through qualitative interviews with laboratory and public health professionals involved in the investigation. The interviews were analysed thematically. From 2017 - 2023, 36 people were linked to a large lineage 4 TB outbreak comprising 3 sub-clusters. WGS connected two patients who were initially not epidemiologically linked to the outbreak, prompting additional contact screening at a medical clinic. From interviews with 10 laboratory and public health professionals, WGS was considered a useful tool, although there was a gap between its potential and realised utility. WGS strengthened confidence in suspected transmission links, which was particularly valuable when epidemiological evidence was sparce or uncertain. This was relevant in this investigation where TB stigma, a prolonged timeframe, and cross-jurisdictional transmission were challenges. Barriers to public health action from WGS included long turnaround times, difficulties drawing conclusions from identical isolates, and uncertainties around public health follow-up actions. This case study demonstrates that WGS can inform meaningful public health action, while also identifying opportunities to improve its utility. WGS for public health should involve real-time sequencing along with steps to support the translation of findings into actions such as action-focused WGS training, mechanisms to support consistent follow-up, and improved record-keeping systems.