Poster Presentation Australian Society for Microbiology Annual Scientific Meeting 2023

Genomic epidemiology of drug resistant tuberculosis in Victoria, Australia (#125)

Thinley Dorji 1 , Kristy Horan 2 , Norelle Sherry 1 2 , Ee Laine Tay 3 , Maria Globan 4 , Linda Viberg 4 , Katherine Bond 4 5 , Justin T Denholm 5 6 7 , Benjamin P Howden 1 2 8 , Patiyan Andersson 1 2
  1. Department of Microbiology and Immunology at The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia
  2. Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology at The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia
  3. Communicable Disease Epidemiology and Surveillance, Health Protection Branch, Public Health Division, Department of Health, Melbourne, Victoria, Australia
  4. Mycobacterium Reference Laboratory, Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia
  5. Royal Melbourne Hospital, , Melbourne, Victoria, Australia
  6. Victorian Tuberculosis Program. Melbourne Health at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia
  7. Department of Infectious Diseases at The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia
  8. Centre for Pathogen Genomics, University of Melbourne, Melbourne, Victoria, Australia

The effective treatment and elimination of Mycobacterium tuberculosis (MTB) has been hampered by the development of drug-resistance. In addition to effective treatment of active cases, the elimination of drug resistant tuberculosis (DR-TB) in low-burden settings such as Australia relies on rapid and efficient contact tracing and surveillance. This is made possible by use of whole genome sequencing (WGS), which can identify clusters, any laboratory cross-contamination events, transmission patterns and drug resistance mutations.

We conducted a retrospective cohort study using whole genome sequences from 152 genomically defined DR-TB isolates collected between 2018-2021 in Victoria, Australia. Bioinformatic analysis was performed to check for resistance type, resistance conferring mutations, lineages, clusters and understand how local sequences compared with international context.

The highest proportion of isolates belonged to lineage 2 (42%) followed by lineage 1 (34%). Genomically, isoniazid mono-resistance (66.9%) was the most frequent resistance identified with mutations in katG and fabG1 genes. Other common mutations were commonly observed in rpoB and embB genes for rifampicin and ethambutol. Mutations were also observed in rpsL, fabG1, gid and rrs gene providing resistance to second-line TB drugs. The common site of mutation in katG was in observed in Ser315Thr and fabG1 -15 C>T. rpoB mutations were commonly seen in Ser450Leu. Phylogenetic analysis of Victorian DR-TB in an international context, indicated that most cases were likely imported from overseas. There was little evidence of local transmission, with only five clusters with two isolates each.

Use of WGS can identify clusters as well as resistance conferring mutations, which can inform prevention and treatment strategies.