Value of routine whole genome sequencing for Mycobacterium tuberculosis drug resistance detection

Connie Lam; Elena Martinez; Taryn Crighton; Catriona Furlong; Ellen Donnan; Ben J Marais; Vitali Sintchenko

doi:10.1016/j.ijid.2021.03.033

Value of routine whole genome sequencing for Mycobacterium tuberculosis drug resistance detection

Int J Infect Dis. 2021 Dec:113 Suppl 1:S48-S54. doi: 10.1016/j.ijid.2021.03.033. Epub 2021 Mar 19.

Authors

Connie Lam¹, Elena Martinez², Taryn Crighton², Catriona Furlong³, Ellen Donnan³, Ben J Marais⁴, Vitali Sintchenko⁵

Affiliations

¹ Centre for Infectious Diseases and Microbiology-Public Health, Westmead Hospital, Western Sydney Local Health District, Sydney, New South Wales, Australia. Electronic address: [email protected].
² NSW Mycobacterium Reference Laboratory, Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, NSW Health Pathology - Western, Sydney, New South Wales, Australia.
³ New South Wales Tuberculosis Program, Health Protection NSW, Sydney, New South Wales, Australia.
⁴ Marie Bashir Institute for Infectious Diseases and Biosecurity and Centre for Research Excellence in Tuberculosis (TB-CRE), The University of Sydney, Sydney, New South Wales, Australia; Children's Hospital at Westmead, Westmead, New South Wales, Australia.
⁵ Centre for Infectious Diseases and Microbiology-Public Health, Westmead Hospital, Western Sydney Local Health District, Sydney, New South Wales, Australia; NSW Mycobacterium Reference Laboratory, Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, NSW Health Pathology - Western, Sydney, New South Wales, Australia; Marie Bashir Institute for Infectious Diseases and Biosecurity and Centre for Research Excellence in Tuberculosis (TB-CRE), The University of Sydney, Sydney, New South Wales, Australia.

PMID: 33753222
DOI: 10.1016/j.ijid.2021.03.033

Abstract

Routine whole genome sequencing (WGS) of pathogens is becoming more feasible as sequencing costs decrease and access to benchtop sequencing equipment and bioinformatics pipelines increases. This study examined the added value gained from implementing routine WGS of all Mycobacterium tuberculosis isolates in New South Wales, Australia. Drug resistance markers inferred from WGS data were compared to commercial genotypic drug susceptibility testing (DST) assays and conventional phenotypic DST in all isolates sequenced between 2016 and 2019. Of the 1107 clinical M. tuberculosis isolates sequenced, 29 (2.6%) were multi-drug resistant (MDR); most belonged to Beijing (336; 30.4%) or East-African Indian (332; 30%) lineages. Compared with conventional phenotypic DST, WGS identified an additional 1% of isolates which were likely drug resistant, explained by mutations previously associated with treatment failure and mixed bacterial populations. However, WGS provided a 20% increase in drug resistance detection in comparison with commercial genotypic assays by identifying mutations outside of the classic resistance determining regions in rpoB, inhA, katG, pncA and embB genes. Gains in drug resistance detection were significant (p = 0.0137, paired t-test), but varied substantially for different phylogenetic lineages. In low incidence settings, routine WGS of M. tuberculosis provides better guidance for person-centered management of drug resistant tuberculosis than commercial genotypic assays.

Keywords: Drug Resistance; Lineage; Multi-drug resistant tuberculosis; Mycobacterium tuberculosis; Tuberculosis; Whole genome sequencing.

MeSH terms

Drug Resistance
Humans
Microbial Sensitivity Tests
Mycobacterium tuberculosis* / genetics
Phylogeny
Whole Genome Sequencing