Lineage-specific transmission and spatial clustering of Mycobacterium tuberculosis in Kaohsiung, Taiwan, in 2019-23: a population-based genomic study.
BACKGROUND: The epidemiology of tuberculosis in Taiwan has been influenced by the introduction of multiple Mycobacterium tuberculosis lineages and by the ageing of the population. We conducted a population-based study to investigate M tuberculosis transmission in Kaohsiung, a city in southern Taiwan. METHODS: In this study, we performed whole-genome sequencing (WGS) of M tuberculosis isolates from all culture-positive cases of tuberculosis notified in Kaohsiung between Jan 1, 2019 and Dec 31, 2023. We obtained routine epidemiological data for each case collected through the national tuberculosis control programme. We characterised the lineage composition of the isolate collection and evaluated genomic clustering of isolates, defined as a difference of 12 or fewer single-nucleotide polymorphisms. Univariable and multivariable logistic regression analyses were performed to estimate the odds of a case belonging to a genomic cluster based on host factors (age, sex, sputum smear status, and residential region) and pathogen factors (drug resistance status and strain lineage). Spatial aggregation of large genomic clusters (including greater than or equal to ten isolates) was assessed using a non-parametric statistical clustering method. We used a Bayesian transmission tree inference method to explore the patterns of age-dependent transmission. FINDINGS: During the study period, 5667 tuberculosis cases were notified in Kaohsiung, 4916 (86·7%) of which were culture-positive. Of these 4916 cases, whole-genome sequencing was successfully performed for 4168 (84·8%) isolates. 1219 (29·2%) of 4168 individuals were female and 2947 (70·7%) were male; the median age was 69·7 years (IQR 57·4-80·7). The dominant lineages were lineage 1 (1749 [42·0%] of 4168 isolates), lineage 2 (1510 [36·2%]), and lineage 4 (905 [21·7%]). 1069 (25·6%) of 4168 were genomically linked and formed 287 clusters. Lineage 2 isolates had higher odds (aOR 2·15 [95% CI 1·80-2·52]) than lineage 1 isolates of genomic clustering across all regions, whereas lineage 4 isolates had a significantly higher risk (2·75 [1·16-6·89]) of genomic clustering than lineage 1 only in the rural northeast region, inhabited primarily by indigenous populations. Spatial clustering analysis corroborated these lineage-region interactions. Although younger adults (<35 years) had the highest individual-level odds (5·64 [4·16-7·68]) of clustering in the logistic regression analysis compared with those aged 80 years or older, the transmission inference indicated that individuals aged 55-74 years were responsible for a greater proportion of inferred transmission events, contributing 50·8% of all transmission events. INTERPRETATION: This sequencing study revealed that older adults (aged ≥65 years) might have played a substantial and under-recognised role in the transmission of tuberculosis in Taiwan. The lineage-specific clustering and spatial patterns suggested that both pathogen characteristics and host demographics shaped tuberculosis transmission dynamics. These findings support the use of integrated genomic surveillance to guide precision tuberculosis control and motivate further research on age-specific transmission pathways and targeted interventions to advance tuberculosis elimination efforts. FUNDING: Taiwan National Health Research Institutes and Taiwan National Science and Technology Council.