Real-Time Molecular Survey of Mycobacterium tuberculosis Isolates from 2008 to 2018 Reveals Tuberculosis Transmission in a Tertiary-Care University Hospital

Background: Molecular survey including whole-genome sequencing (WGS) of Mycobacterium tuberculosis isolates is a reliable tool to reveal clonal outbreaks. Here, both genomic and epidemiological investigations were coupled in a prospective approach to assess nosocomial tuberculosis (TB) transmission in a tertiary-care hospital. Methods: Since 2008, the Mycobacteria laboratory of the Lyon university hospital, has implemented a prospective population-based survey by systematic genotyping (first using spoligo- and MIRU typing, and WGS since 2017) of M. tuberculosis isolates in the Rhone-Alpes region. Conventional contact-tracing of TB cases was conducted in accordance with French guidelines. Findings: Since 2008, among 3230 cases of microbiologically-proven TB, 96 molecular clusters with confirmed transmissions were identified. Four clusters were health care-related, representing eight patients, including three independent transmissions of susceptible M. tuberculosis in lung transplant recipients, and one transmission of a multi-resistant strain. Epidemiological investigation validated nosocomial transmissions in these four health care-related clusters. One nosocomial transmission was imbedded in a much larger community transmission chain involving ten patients. Corrective measures implemented were to discard any admission of TB patients in the transplant surgery hospital, and to construct a building equipped with negative-pressure ventilation rooms dedicated to TB management. Interpretation: TB molecular survey is a valuable strategy to detect unsuspected transmission chains, particularly among health-care facilities. Prospective monitoring and tight partnership with public health agencies render survey-guided prevention control measures possible. Funding Statement: LABEX ECOFECT (ANR-11-LABX-0048) of the Lyon University as part of the research program "Investissements d'Avenir" (ANR-11-IDEX-0007) operated by the French National Research Agency (ANR). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The study was approved by the Lyon University Hospital Ethical Committee.