Tuberculosis (TB) control continues to pose a global challenge. A better understanding of the differences between Mycobacterium tuberculosis strains isolated from respiratory and non-respiratory sources may inform clinical care and control strategies.
We conducted an analysis of all culture-confirmed TB cases notified in New South Wales (NSW), Australia, from January 2017 and December 2021. Demographic and genomic characteristics of M. tuberculosis cultures based on the specimen source (respiratory vs. non-respiratory) were examined and compared using uni- and multi-variable logistic regression models.
M. tuberculosis strains from 1,831 patients were sequenced; 64.8% of all notified TB cases. Of these isolates, 64.7% were from respiratory, 32.1% from non-respiratory and 2.2% from both respiratory and non-respiratory sources. On multivariate analysis female patients had more frequent isolation from a non-respiratory source (p=0.03), and older adults (≧65 years) from a respiratory source (p<0.0001). Compared to non-respiratory isolates, respiratory isolates were more frequently part of a genomic transmission clusters (p=0.001) or associated with drug resistance (p=0.12). Lineage 2 strains were over-represented among respiratory isolates (p=0.01) and lineage 3 among non-respiratory isolates (p=0.0005). Among 39 TB cases with sequenced isolates from both respiratory and non-respiratory sources, 17 (43.6%) had single nucleotide polymorphisms (SNP) differences - ranging from 1-10 SNPs.
This is the first comprehensive description of genomic differences between respiratory and non-respiratory isolates. The finding that older adults were more likely to have M. tuberculosis isolated from a respiratory source has relevance for TB control given the expected rise of TB among older adults.