Mapping the origin and spread of Mycobacterium tuberculosis complex in the Tasmanian population using whole-genome sequence and epidemiological data analyses

Background: Tasmania is a small island state in Australia with a population of approximately 0.5 million people. Tuberculosis (TB) in the state peaked at 248 cases in 1947 but has since declined in prevalence. Today, Tasmania is considered a low TB-burden state with an incidence rate of 1.8 per 100,000 persons compared to 5.8 per 100,000 nationally in 2014. There are a number of interesting factors regarding TB in the state. Firstly, TB in Tasmania has long been considered to consist of isolated cases imported from other jurisdictions. Secondly, it is believed to be free of multi-drug resistant forms of TB. Thirdly, bovine TB was eradicated from cattle herds in 1975 which essentially eliminated human cases of M. bovis TB in Tasmania.

Experimental Approach: In this work, we performed whole-genome sequencing of cultured isolates of Mycobacterium tuberculosis complex from 2014-2016 to better understand the epidemiology of TB in Tasmania. We correlated genomic information with clinical records and public health surveillance data.

Results: We identified two probable clusters of the disease during the above time period. One of the clusters occurred from May to August 2015 in individuals (n=4) from Nepal. The second cluster occurred between November and December 2014 in individuals (n=2) from New Zealand. Our genomic data has established that these isolates are identical based on singlelocus variant analysis and therefore, constitute confirmed clusters of TB in Tasmania. Here we also report the first known case of MDR-TB in Tasmania. We examined the clinical record of this case that occurred in 2016 and extracted evidence from the genome of the MDR-TB isolate with regard to its resistance and origin. In addition, we report on a case of pulmonary TB in a Tasmanian-born individual in 2015 due to M. bovis and discuss how it may have appeared post the completion of the Brucellosis and Tuberculosis Eradication Campaign in Australia.

Conclusions: Tasmania exhibits features of TB observed in other jurisdictions, namely clustering of cases and the emergence of drug resistance. Hence, the state is not immune to major risks associated with TB globally. Early detection of TB and contact tracing, coordinated with rapid laboratory diagnosis, drug-susceptibility testing and molecular typing, are essential for effective control of the spread of TB in Tasmania.