CliniCon Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2023

Benchmarks for tuberculosis control that incorporate routine whole genome sequencing (#220)

Xiaomei Zhang 1 2 , Elena Martinez 2 3 , Connie Lam 2 4 , Taryn Crighton 3 5 , Eby Sim 2 4 , Ellen Donnan 6 , Ben Marais 1 2 , Vitali Sintchenko 1 2 4 5 , Mailie Gall 2 5
  1. Centre for Research Excellence in Tuberculosis (TB-CRE), Centenary Institute, Sydney, NEW SOUTH WALES, Australia
  2. Sydney Infectious Diseases Institute, The University of Sydney, Sydney, New South Wales, Australia, Sydney, New South Wales, Australia
  3. Centre for Infectious Diseases and Microbiology-Laboratory Services, Westmead Hospital, Western Sydney Local Health District, Sydney, New South Wales, Australia
  4. Centre for Infectious Diseases and Microbiology-Public Health, Westmead Hospital, Western Sydney Local Health District, Sydney, New South Wales, Australia
  5. NSW Mycobacterium Reference Laboratory, Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, NSW Health Pathology , Sydney, New South Wales, Australia
  6. New South Wales Tuberculosis Program, Health Protection NSW, Sydney, New South Wales, Australia, Sydney, New South Wales, Australia

Routine whole genome sequencing of Mycobacterium tuberculosis has been implemented with increasing frequency. However, its value for enhanced tuberculosis (TB) control and novel benchmarks to assess this, have not been explored. 

We analysed routine sequencing data of culture-confirmed TB cases notified between 1st January 2017 and 31st December 2021 in New South Wales, Australia.  Genomic surveillance included drug-resistance conferring mutations and evidence of local TB transmission, defined by single nucleotide polymorphism (SNP) clustering over a variable (0-25) SNP threshold. 

M. tuberculosis sequences from 1831 patients were analysed, representing 64.8% of all notified TB cases and 96.2% of culture-confirmed cases. Genotypic drug susceptibility testing (DST) was highly concordant with phenotypic DST, facilitated surveillance of drug resistance mutations and provided a 6.6% ‘value add’ for antimycobacterial resistance detection. Beijing strains were more likely to be drug resistant (p=0.04) and locally transmitted if drug resistant (p=0.01). The application of a traditional 5-SNP cluster threshold identified 62 clusters with 183 clustered cases and an estimated rate of recent transmission (RRT) of 6.8%. Of these clustered cases 104/183 (56.8%) had 0 SNP differences, which is highly indicative of person-to-person transmission. A lineage-specific 5-year cluster assessment provided a comprehensive overview of recent transmission within Australia.

Routine WGS offers an opportunity to implement new benchmarks for TB control, such as using a rolling 5-year cluster assessment, as an indicator of effective epidemic containment. Genomic DST also provides valuable information for clinical care and drug resistance surveillance.