Whole genome sequencing for Mycobacterium tuberculosis in public health responses: a review of current practice and enablers in select low-incidence jurisdictions.

backgroundWhile whole-genome sequencing (WGS) of Mycobacterium tuberculosis is increasingly performed, there has been uncertainty about the optimal integration of results into real-time public health practice. This manuscript describes programmatic activities from invited jurisdictions utilising WGS results to guide tuberculosis (TB) public health responses, including the current approaches to genomic data interpretation, engagement with clinical and epidemiological services, and evaluation of public health impact.

methodsJurisdictions performing routine real-time TB WGS and using findings for directing public health activity were identified and approached for inclusion. Participating jurisdictions provided information on current policy and practice through a survey and semi-structured key informant interviews, and additional information was collected through review of publicly available sources. Public health responses were described and classified at micro (individual), meso (population) and macro (policy) levels. Additional information on perceived public health impact and community engagement was also sought.

resultsEight low-incidence jurisdictions from North America, Europe, Asia and Australia were identified, and all participated. All participating jurisdictions employed routine WGS both for genotypic drug susceptibility testing (gDST) and for assessing local transmission dynamics. Programs reported a variety of structures for analysis and dissemination of findings, including the role of multidisciplinary teams for interpretation and systems for interjurisdictional data sharing. Programs used WGS to guide clinical decision-making and outbreak management, including targeted active case finding and contact management, assessment of potential laboratory contamination events, and monitoring of long-term transmission trends. Existing evaluation of WGS was primarily process-driven, with limited evaluation of public health impact, although program performance metrics have been proposed.

conclusionsWGS is increasingly used for TB public health activities, with a variety of systems established for implementation. Future work should refine best-practices in using WGS for optimal public health impact, including strengthening monitoring and evaluation of TB programs, defining consensus benchmarks as key indicators of program performance and considering opportunities for impact in lower-resource settings.