Volume 99, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



We used whole-genome sequencing to investigate a tuberculosis outbreak involving U.S.-born persons in the prison system and both U.S.- and foreign-born persons in the community in Florida over a 7-year period (2009–2015). Genotyping by spacer oligonucleotide typing and 24-locus mycobacterial interspersed repetitive unit-variable number tandem repeat suggested that the outbreak might be clonal in origin. However, contact tracing could not link the two populations. Through a multidisciplinary approach, we showed that the cluster involved distinct bacterial transmission networks segregated by country of birth. The source strain is of foreign origin and circulated in the local Florida community for more than 20 years before introduction into the prison system. We also identified novel transmission links involving foreign and U.S.-born cases not discovered during contact investigation. Our data highlight the potential for spread of strains originating from outside the United States into U.S. “high-risk” populations, such as prisoners, with subsequent movement back to the general community.

[open-access] This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. Castro KG, Jaffe HW, , 2002. Rationale and methods for the national tuberculosis genotyping and surveillance network. Emerg Infect Dis 8: 11881191. [Google Scholar]
  2. Crawford JT, Braden CR, Schable BA, Onorato IM, , 2002. National tuberculosis genotyping and surveillance network: design and methods. Emerg Infect Dis 8: 11921196. [Google Scholar]
  3. Moonan PK, Ghosh S, Oeltmann JE, Kammerer JS, Cowan LS, Navin TR, , 2012. Using genotyping and geospatial scanning to estimate recent Mycobacterium tuberculosis transmission, United States. Emerg Infect Dis 18: 458465. [Google Scholar]
  4. Yuen CM, Kammerer JS, Marks K, Navin TR, France AM, , 2016. Recent transmission of tuberculosis—United States, 2011–2014. PLoS One 11: e0153728. [Google Scholar]
  5. Ghosh S, Moonan PK, Cowan L, Grant J, Kammerer S, Navin TR, , 2012. Tuberculosis genotyping information management system: enhancing tuberculosis surveillance in the United States. Infect Genet Evol 12: 782788. [Google Scholar]
  6. Kato-Maeda M, Metcalfe JZ, Flores L, , 2011. Genotyping of Mycobacterium tuberculosis: application in epidemiologic studies. Future Microbiol 6: 203216. [Google Scholar]
  7. Daley CL, Kawamura LM, , 2003. The role of molecular epidemiology in contact investigations: a US perspective. Int J Tuberc Lung Dis 7: S458S462. [Google Scholar]
  8. Gardy JL, 2011. Whole-genome sequencing and social-network analysis of a tuberculosis outbreak. N Engl J Med 364: 730739. [Google Scholar]
  9. Walker TM, 2013. Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks: a retrospective observational study. Lancet Infect Dis 13: 137146. [Google Scholar]
  10. Didelot X, Fraser C, Gardy J, Colijn C, , 2017. Genomic infectious disease epidemiology in partially sampled and ongoing outbreaks. Mol Biol Evol 34: 9971007. [Google Scholar]
  11. Hatherell HA, Didelot X, Pollock SL, Tang P, Crisan A, Johnston JC, Colijn C, Gardy JL, , 2016. Declaring a tuberculosis outbreak over with genomic epidemiology. Microb Genom 2: e000060. [Google Scholar]
  12. Centers for Disease Control and Prevention, 2009. Report of Verified Case of Tuberculosis (RVCT): Instruction Manual, 162. Available at: http://www.cdc.gov/tb/programs/rvct/InstructionManual.pdf. Accessed May 23, 2016.
  13. Bolger AM, Lohse M, Usadel B, , 2014. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30: 21142120. [Google Scholar]
  14. Nguyen L-T, Schmidt HA, von Haeseler A, Minh BQ, , 2015. IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies. Mol Biol Evol 32: 268274. [Google Scholar]
  15. Rambaut A, Lam TT, Max Carvalho L, Pybus OG, , 2016. Exploring the temporal structure of heterochronous sequences using TempEst (formerly Path-O-Gen). Virus Evol 2: vew007. [Google Scholar]
  16. Francisco AP, Vaz C, Monteiro PT, Melo-Cristino J, Ramirez M, Carriço JA, , 2012. PHYLOViZ: phylogenetic inference and data visualization for sequence based typing methods. BMC Bioinformatics 13: 87. [Google Scholar]
  17. Kumar S, Stecher G, Tamura K, , 2016. MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol Biol Evol 33: 18701874. [Google Scholar]
  18. Ford CB, Shah RR, Maeda MK, Gagneux S, Murray MB, Cohen T, Johnston JC, Gardy J, Lipsitch M, Fortune SM, , 2013. Mycobacterium tuberculosis mutation rate estimates from different lineages predict substantial differences in the emergence of drug-resistant tuberculosis. Nat Genet 45: 784790. [Google Scholar]
  19. Drummond AJ, Rambaut A, , 2007. BEAST: Bayesian evolutionary analysis by sampling trees. BMC Evol Biol 7: 214. [Google Scholar]
  20. Didelot X, Gardy J, Colijn C, , 2014. Bayesian inference of infectious disease transmission from whole-genome sequence data. Mol Biol Evol 31: 18691879. [Google Scholar]
  21. Stucki D, 2016. Standard genotyping overestimates transmission of Mycobacterium tuberculosis among immigrants in a low-incidence country. J Clin Microbiol 54: 18621870. [Google Scholar]
  22. Lee RS, 2015. Reemergence and amplification of tuberculosis in the Canadian arctic. J Infect Dis 211: 19051914. [Google Scholar]
  23. Gurjav U, Outhred AC, Jelfs P, McCallum N, Wang Q, Hill-Cawthorne GA, Marais BJ, Sintchenko V, , 2016. Whole genome sequencing demonstrates limited transmission within identified Mycobacterium tuberculosis clusters in New South Wales, Australia. PLoS One 11: e0163612. [Google Scholar]
  24. Niemann S, Supply P, , 2014. Diversity and evolution of Mycobacterium tuberculosis: moving to whole-genome-based approaches. Cold Spring Harb Perspect Med 4: a021188. [Google Scholar]
  25. Walker TM, Monk P, Grace Smith E, Peto TEA, , 2013. Contact investigations for outbreaks of Mycobacterium tuberculosis: advances through whole genome sequencing. Clin Microbiol Infect 19: 796802. [Google Scholar]
  26. Crawford JT, , 2003. Genotyping in contact investigations: a CDC perspective. Int J Tuberc Lung Dis 7 (Suppl 3): S453S457. [Google Scholar]
  27. Centers for Disease Control and Prevention (CDC), 2012. Notes from the field: tuberculosis cluster associated with homelessness—Duval County, Florida, 2004–2012. MMWR Morb Mortal Wkly Rep 61: 539540. [Google Scholar]
  28. Duarte R, Neto M, Carvalho A, Barros H, , 2012. Improving tuberculosis contact tracing: the role of evaluations in the home and workplace. Int J Tuberc Lung Dis 16: 5559. [Google Scholar]
  29. Worby CJ, Lipsitch M, Hanage WP, , 2014. Within-host bacterial diversity hinders accurate reconstruction of transmission networks from genomic distance data. PLoS Comput Biol 10: e1003549. [Google Scholar]
  30. Lieberman TD, Wilson D, Misra R, Xiong LL, Moodley P, Cohen T, Kishony R, , 2016. Genomic diversity in autopsy samples reveals within-host dissemination of HIV-associated Mycobacterium tuberculosis. Nat Med 22: 14701474. [Google Scholar]
  31. Hatherell HA, Colijn C, Stagg HR, Jackson C, Winter JR, Abubakar I, , 2016. Interpreting whole genome sequencing for investigating tuberculosis transmission: a systematic review. BMC Med 14: 21. [Google Scholar]
  32. Kaeble D, Glaze L, , 2016. Correctional Populations in the United States, 2015, 20. U.S. Department of Justice. Available at: https://www.bjs.gov/content/pub/pdf/cpus15.pdf. Accessed July 25, 2017.
  33. Carson AE, Anderson E, , 2016. Prisoners in 2015, 35. U.S. Department of Justice. Available at: https://www.bjs.gov/content/pub/pdf/p15.pdf. Accessed July 31, 2017.
  34. Bick JA, , 2007. Infection control in jails and prisons. Clin Infect Dis 45: 10471055. [Google Scholar]
  35. Hammett TM, Harmon MP, Rhodes W, , 2002. The burden of infectious disease among inmates of and releasees from US correctional facilities, 1997. Am J Public Health 92: 17891794. [Google Scholar]
  36. Achtman M, , 2008. Evolution, population structure, and phylogeography of genetically monomorphic bacterial pathogens. Annu Rev Microbiol 62: 5370. [Google Scholar]
  37. Stucki D, 2015. Tracking a tuberculosis outbreak over 21 years: strain-specific single-nucleotide polymorphism typing combined with targeted whole-genome sequencing. J Infect Dis 211: 13061316. [Google Scholar]
  38. Nikolayevskyy V, Kranzer K, Niemann S, Drobniewski F, , 2016. Whole genome sequencing of Mycobacterium tuberculosis for detection of recent transmission and tracing outbreaks: a systematic review. Tuberculosis (Edinb) 98: 7785. [Google Scholar]

Data & Media loading...

Supplemental information, tables, and figures

  • Received : 06 Sep 2017
  • Accepted : 18 May 2018
  • Published online : 09 Jul 2018

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error