Transmission between HIV-infected patients of multidrug-resistant tuberculosis caused by Mycobacterium bovis

Objective: To investigate outbreaks of multidrug-resistant tuberculosis (TB) by using DNA fingerprint databases. Design: Investigation of two outbreaks of multidrug-resistant TB in separate hospitals in Spain by restriction fragment length polymorphism (RFLP) and spoligotyping. Outbreak strains were compared with more than 1500 RFLPs of Mycobacterium tuberculosis complex strains isolated in Spain and 6000 RFLPs from 30 different countries. Methods: Standardized IS6110 DNA fingerprinting and 'spoligotyping' was used to type multidrug-resistant isolates belonging to the M. tuberculosis complex amongst the outbreak cases. The DNA types were matched against DNA fingerprint databases in Spain and The Netherlands. Results: The DNA typing analysis indicated that a single multidrug-resistant Mycobacterium bovis strain was responsible for a nosocomial outbreak in a hospital in Spain involving at least 16 HIV-infected patients with non-treatable to multidrug-resistant TB. Introduction of the fingerprint type of this strain to the international database revealed a single matching strain. This strain was also isolated from an HIV-infected patient in The Netherlands who had died from multidrug-resistant TB. This patient had previously been hospitalized in Spain, where a multidrug-resistant TB nosocomial outbreak involving 20 HIV-infected patients was ongoing. The strains causing this outbreak were also identified as M. bovis with an identical DNA pattern to those strains isolated in the Spanish hospital and the patient in The Netherlands. Conclusions: The use of centralized DNA databases can help to identify rapidly the origin and transmission routes of multidrug-resistant TB across international boundaries and the potential use of such an early warning surveillance system for investigation of nosocomial multidrug-resistant TB outbreaks between HIV-infected patients. To our knowledge this is the first report of transmission of multidrug-resistant M. bovis between hospitals.