Abstract

.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.

Highlights

  • IntroductionIn the United States, universal and systematic genotyping of Mycobacterium tuberculosis cases by spacer oligonucleotide typing (spoligotyping) and 24-locus mycobacterial interspersed repetitive unit–variable number tandem repeat (MIRU-VNTR) typing through the U.S National Tuberculosis (TB) Genotyping Service has been instrumental in the understanding of the molecular epidemiology of TB.[1,2] The service monitors progress toward elimination by quantifying recent TB transmission rates.[3,4] Genotyping has greatly improved TB prevention and control efforts in the United States by facilitating the prompt identification and treatment of latently infected cases.[1,5] the system is not without limitations

  • In the United States, universal and systematic genotyping of Mycobacterium tuberculosis cases by spacer oligonucleotide typing and 24-locus mycobacterial interspersed repetitive unit–variable number tandem repeat (MIRU-VNTR) typing through the U.S National Tuberculosis (TB) Genotyping Service has been instrumental in the understanding of the molecular epidemiology of TB.[1,2]

  • One inmate (I) died of causes unrelated to TB disease in 2011 and Through a multidisciplinary approach, we showed that a putative single outbreak first identified using traditional genotyping markers involved distinct bacterial transmission networks segregated by country of birth

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Summary

Introduction

In the United States, universal and systematic genotyping of Mycobacterium tuberculosis cases by spacer oligonucleotide typing (spoligotyping) and 24-locus mycobacterial interspersed repetitive unit–variable number tandem repeat (MIRU-VNTR) typing through the U.S National Tuberculosis (TB) Genotyping Service has been instrumental in the understanding of the molecular epidemiology of TB.[1,2] The service monitors progress toward elimination by quantifying recent TB transmission rates.[3,4] Genotyping has greatly improved TB prevention and control efforts in the United States by facilitating the prompt identification and treatment of latently infected cases.[1,5] the system is not without limitations. In cases where a genotype cluster cannot be resolved by contact tracing, whole-genome sequencing (WGS) can be implemented selectively as a secondary genotyping step to describe TB clusters at a higher resolution.[8,9] WGS provides unprecedented resolution to TB outbreak investigation, traditional epidemiological investigation of contacts is still crucial to define transmission links.[8,9] Retrospective evaluation of genotype clusters may benefit from contemporary methods that combine genomic data with mathematical models to reconstruct TB outbreaks and provide TB control programs with actionable information, such as the probability of person-to-person transmission within TB clusters.[10,11]

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