Mycobacterium tuberculosis transmission dynamics within prisons: a population-based genomic study

<h2>Summary</h2><h3>Background</h3> One barrier to intervening in the global tuberculosis pandemic is that it is unknown whether <i>Mycobacterium tuberculosis</i> transmission largely occurs through repeated close exposures among few contacts or many shorter-term contacts. Identifying sources of transmission is particularly urgent in congregate settings like prisons with high incidence of infection. Our aim was to identify the type of contacts associated with <i>M. tuberculosis</i> transmission risk within prisons. <h3>Methods</h3> We conducted genomic surveillance in a prison system in Central West Brazil. We whole genome sequenced <i>M. tuberculosis</i> isolates and collected detailed incarceration histories. We modeled transmission linkages as a function of different types of prison exposures, using genomic clustering as a proxy for transmission and controlling for multiple pairwise comparisons. <h3>Findings</h3> We collected detailed incarceration histories for 595 individuals, mean age 31 (ST—standard deviation 8.5) and 99% men, from whom we sequenced 550 high quality <i>M. tuberculosis</i> genomes. In a binomial model, a month-long increase in exposure to an individual with tuberculosis within a prison cell increased the odds of pairwise genomic clustering by 14% (odds ratio—OR: 1.14, 95% CI: 1.09–1.19) and a six-month increase in exposure doubled the odds of genomic clustering (OR: 2.24, 95% CI: 1.73–2.91). Most (83%; 494 of 595) individuals with tuberculosis had at least one potential day-long exposure in a prison cell to another individual with tuberculosis, and frequently many, with a median of 8 (interquartile range—IQR: 4–12) potential unique exposures to individuals in prison cells. Frequent movements by the prison system create a highly connected contact network: individuals with tuberculosis were transferred a median of 8 (IQR: 4–13) times in the 2 years before diagnosis. <h3>Interpretation</h3> While documented cell-level exposures can explain a significant proportion of <i>M. tuberculosis</i> transmission, most transmission links occur outside prison cells, either from other contacts in the same prison or from unreported or unsampled exposures. Our results support the urgent expansion of prison-wide mass screenings, tuberculosis preventive therapy, and structural interventions to reduce transmission risk in prisons and other congregate settings. <h3>Funding</h3> National Institutes of Health (NIAID: 5K01AI173385, R01AI100358, and R01AI149620).