Background
Tuberculosis is a global public health concern. Genomic analysis of Mycobacterium tuberculosis (Mtb) has been at a state or territory level, and cross-jurisdictional epidemiology of Mtb in Australia remains poorly understood. We present the first national assessment of Mtb drug resistance and genomic clusters using a decade of genomic data from Australian jurisdictions, as a part of the Australian Pathogen Genomics program.
Methods
Our national dataset of Mtb sequences included retrospective (2015-2022) and 2023 snapshot data, aiming to represent Mtb notifications of culture-confirmed disease. Mtb genomic surveillance was established on AusTrakka, allowing Public Health Laboratories to securely contribute Mtb genomes and metadata. Hierarchical (0, 5 and 12 SNPs) single linkage clustering from pairwise SNP distances were used to identify genomic clusters, and the tbtAMR tool was used for drug resistance prediction. Metadata was combined with genomic analysis to identify Mtb clusters of national public health significance.
Results
6,670 Mtb sequences (retrospective=5,915; snapshot=692) representing cases across all states and territories were examined and comprised 55.49% of all notified cases in Australia from 2015-2023. Mtb lineages 1-4 were detected, with Lineage 2 being the most prevalent and drug resistant. At the 5-SNP threshold, 373 genomic clusters were identified, with the number of genomic clusters increasing to 422 when a relaxed threshold of 12 was applied. Of the 373 genomic clusters, 48 were identified as having public health significance. 31 Mtb genomic clusters spanned multiple jurisdictions with many persisting for >5 years and those with >15 sequences all multijurisdictional. Genotypically inferred drug susceptibility revealed low rates of multidrug resistance in Australian Mtb.
Conclusions
This first-of-a-kind study on Australian Mtb highlights the benefits of undertaking coordinated national sequencing in Australia. Real-time cluster and AMR identification can enhance Mtb control and surveillance in Australia and are essential to minimise Mtb transmission events in a low-incidence country.