Infectious Disease
Using spatial and genomic analyses to investigate Mycobacterium tuberculosis transmission in a large city in Taiwan Yu Lan* Yu Lan Chieh-Yin Wu Benjamin Sobkowiak Joshua L. Warren Ted Cohen Hsien-Ho Lin
Background: The estimated incidence of tuberculosis (TB) in Taiwan has declined by an average of 6% a year since 2016 and was at 28 cases/100,000 individuals in 2022. In the setting of declining disease and increasing concentration in old age groups, a better understanding of where and amongst whom transmission of Mycobacterium tuberculosis (Mtb) is occurring can help inform elimination strategies.
Design: We aimed to sequence Mtb isolates from culture-positive cases in Kaohsiung between 2018-2022. Laboratory and epidemiological data were available from routinely collected records.
Methods: Mtb isolates were grouped into putative transmission clusters based on a standard single nucleotide polymorphism distance threshold of 12. Investigation of spatial foci of transmission was done using a non-parametric distance-based approach. Analysis of factors associated with membership in a transmission pair was done using a hierarchical Bayesian regression model.
Results: Among 4,064 culture-positive cases of TB during the study period, whole genome sequencing data was available for 3,379 cases. We found 217 genomic transmission networks comprising 796 cases, while 11 networks included at least 10 cases. We detected statistically significant spatial foci in 9 large networks. Pairwise analysis revealed that younger ages, smaller age differences, and shorter spatial distance between two patients were associated with greater odds of two patients being in the same network. For every two-year decrease in the sum of ages of two patients, the odds of being in the same network increased by 12% (95%CI: 10%-14%); for every two-year decrease in age difference between two patients, the odds increased by 5% (3%-7%); and for every 5km decrease in spatial distance between two patients, the odds increased by 24% (16%-30%).
Conclusion: Integrating spatial and genomic analysis provide evidence of local Mtb transmission and reveal factors associated with being a member of a transmission pair, including younger total age, more similar age, and smaller distance for the pair.