Real-time molecular survey of Mycobacterium tuberculosis isolates from 2008 to 2018 reveals tuberculosis transmission in a tertiary-care university hospital. Tuberculosis transmission in tertiary-care hospital

Background. Molecular survey by 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 Rhône-Alpes region. Traditional 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 transmissions of susceptible M. tuberculosis in lung transplant recipients and one transmission of a multi-resistant strain. Epidemiological investigation validated nosocomial transmissions. The results from this survey revealed that 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.