Bainomugisa, Arnold

Meumann, Ella M

Rajahram, Giri Shan

Ong, Rick Twee-Hee

Coin, Lachlan

Paul, Dawn Carmel

William, Timothy

Coulter, Christopher

Ralph, Anna P

2021-05

Tuberculosis is a leading public health priority in eastern Malaysia. Knowledge of the genomic epidemiology of tuberculosis can help tailor public health interventions. Our aims were to determine tuberculosis genomic epidemiology and characterize resistance mutations in the ethnically diverse city of Kota Kinabalu, Sabah, located at the nexus of Malaysia, Indonesia, Philippines and Brunei. We used an archive of prospectively collected Mycobacterium tuberculosis samples paired with epidemiological data. We collected sputum and demographic data from consecutive consenting outpatients with pulmonary tuberculosis at the largest tuberculosis clinic from 2012 to 2014, and selected samples from tuberculosis inpatients from the tertiary referral centre during 2012-2014 and 2016-2017. Two hundred and eight M. tuberculosis sequences were available for analysis, representing 8 % of cases notified during the study periods. Whole-genome phylogenetic analysis demonstrated that most strains were lineage 1 (195/208, 93.8 %), with the remainder being lineages 2 (8/208, 3.8 %) or 4 (5/208, 2.4 %). Lineages or sub-lineages were not associated with patient ethnicity. The lineage 1 strains were diverse, with sub-lineage 1.2.1 being dominant (192, 98 %). Lineage 1.2.1.3 isolates were geographically most widely distributed. The greatest diversity occurred in a border town sub-district. The time to the most recent common ancestor for the three major lineage 1.2.1 clades was estimated to be the year 1966 (95 % HPD 1948-1976). An association was found between failure of culture conversion by week 8 of treatment and infection with lineage 2 (4/6, 67 %) compared with lineage 1 strains (4/83, 5 %) (P<0.001), supporting evidence of greater virulence of lineage 2 strains. Eleven potential transmission clusters (SNP difference ≤12) were identified; at least five included people living in different sub-districts. Some linked cases spanned the whole 4-year study period. One cluster involved a multidrug-resistant tuberculosis strain matching a drug-susceptible strain from 3 years earlier. Drug resistance mutations were uncommon, but revealed one phenotype-genotype mismatch in a genotypically multidrug-resistant isolate, and rare nonsense mutations within the katG gene in two isolates. Consistent with the regionally mobile population, M. tuberculosis strains in Kota Kinabalu were diverse, although several lineage 1 strains dominated and were locally well established. Transmission clusters - uncommonly identified, likely attributable to incomplete sampling - showed clustering occurring across the community, not confined to households or sub-districts. The findings indicate that public health priorities should include active case finding and early institution of tuberculosis management in mobile populations, while there is a need to upscale effective contact investigation beyond households to include other contacts within social networks.

Queensland Mycobacterium Reference Laboratory, Brisbane, Australia.

Department of Medicine, Royal Darwin Hospital, Northern Territory, Australia.

Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Northern Territory, Australia.

Clinical Research Centre, Queen Elizabeth Hospital, Sabah, Malaysia.

Department of Medicine, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia.

Infectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Sabah, Malaysia.

Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.

Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.

Kota Kinabalu Public Health Laboratory, Sabah, Malaysia.

Gleneagles Hospital Kota Kinabalu, Sabah, Malaysia.

Microb Genom. 2021 May;7(5). doi: 10.1099/mgen.0.000573.

https://pubmed.ncbi.nlm.nih.gov/33945455/?otool=iaurydwlib

https://hdl.handle.net/10137/11756

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Genomic epidemiology of tuberculosis in eastern Malaysia: insights for strengthening public health responses.

Journal Article

Publication