M. tuberculosistransmission dynamics in congregate settings: a genomic epidemiology study
Authors: Walter Katharine S. , Lemos Everton Ferreira , Alves Ana Paula Cavalcante Aires , Ferreira Gabriela Felix Chaves , Coutinho Vanessa Maruyama Martins , Mathema Barun , Warren Joshua L. , Colijn Caroline , Cohen Ted , Croda Julio , Andrews Jason R. 
Published: January 2025

AbstractBackgroundOne barrier to intervening in the global tuberculosis (TB) pandemic is that it is unknown whetherM. tuberculosistransmission largely occurs through repeated close exposures among few contacts or many shorter-term contacts. Identifying sources of transmission is particularly urgent in congregate settings with high incidence of infection.MethodsTo identify drivers ofM. tuberculosistransmission within a congregate setting with extremely high incidence of TB, we conducted genomic surveillance in a prison system in Central West Brazil. We whole genome sequencedM. tuberculosisisolates and collected detailed incarceration histories, including movements between and within prisons. We integrated incarceration histories withM. tuberculosisgenomes to investigate the relationship between exposures of differing proximity (cell, cell block, prison) and transmission risk, using genomic clustering as a proxy for transmission.FindingsWe collected detailed incarceration histories for 595 individuals from whom we sequenced 561 high qualityM. tuberculosisgenomes. A month-long increase in exposure to an individual with TB within a prison cell increased the odds of pairwise genomic clustering by 7.4% (95% CI: 4.4-10.4%) and a six-month increase in exposure, by 54% (95% CI: 29.9%-82.5%). Most (89%; 528 of 595) individuals with TB had at least one potential week-long exposure in a prison cell to another individual with TB, and frequently many, with a median of 12 (IQR: 5-21) potential unique exposures to individuals in prison cells. Frequent movements by the prison system create a highly connected contact network: individuals with TB were transferred a median of 5 (IQR: 1-17) times in the 12 months before diagnosis.InterpretationWhile close exposures within a prison were related to pairwise genomic clustering, most individuals with TB had multiple exposures to other individuals with TB due to frequent movements by the prison system. Our results support the urgent expansion of prison-wide mass screenings, TB preventive therapy, and structural interventions to reduce transmission risk in prisons and other congregate settings.FundingNational Institutes of Health (NIAID: 5K01AI173385, R01AI100358, and R01AI149620)Research in contextEvidence before this studyWe searched PubMed for relevant articles published in English from database inception to November 26, 2024, using the terms “Mycobacterium tuberculosis”, “transmission,” “genom*,” and “congregate setting” or “prison.” We found several genomic epidemiology articles describing close genetic relatedness ofM. tuberculosissampled from prisons and the community. These earlier genomic epidemiology studies did not include individual-level exposure or movement information. We additionally identified two studies that conducted environmental sampling in congregate settings: one that identifiedM. tuberculosisDNA in bioaerosols in a primary care clinic and one from environmental swabs collected in a prison. Previous studies did not investigate the types of contacts driving transmission in high-incidence congregate settings.Added value of this studyWe conducted a genomic epidemiology study ofM. tuberculosistransmission in a congregate setting with extremely high incidence of tuberculosis (TB): a state prison system in Central West, Brazil. We integratedM. tuberculosisgenomes with detailed individual movement data to reconstruct transmission linkages and infer the types of contacts associated with transmission in a congregate setting. We found that close contacts within a prison—incarceration within the same prison cell—increase the likelihood of transmission. Further, the frequent movement of individuals within and between prisons creates large, highly connected large contact networks. The result is that individuals have many close contacts with other individuals with tuberculosis, such that any single potential exposure may not result in genetically linked cases.Implications of all the available evidenceTogether, our results suggest that close exposures to other individuals with TB increase transmission risk in congregate settings with high incidence of TB. Due to frequent transfers within prison systems, people may have close exposures to many individuals with TB, with the result that contact tracing investigations may not be effective in such settings. Our results support the urgent expansion of mass screenings, TB preventive therapy, and structural interventions to reduce transmission risk in prisons and other congregate settings.