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BACKGROUND. The progenitors of multidrug-resistant tuberculosis (MDR-TB) outbreak strains might evolve into new outbreak strains. We hypothesized that these strains could re-emerge among post-outbreak patients with TB and must thus be tracked. METHODS. To identify the progenitors of the outbreak strain, we first determined the precise IS6110 genomic insertion locations of a Haarlem3 strain that caused a severe MDR-TB outbreak in Tunisia. Next, we searched by polymerase chain reaction for these outbreak-specific IS6110 transposition sites in all the Haarlem3 post-outbreak isolates recovered in the epidemic region. RESULTS. By analyzing the distribution of the outbreak-specific IS6110 transposition sites, we were able to trap, among isolates recovered from post-outbreak new patients, drug-susceptible and drug-resistant isolates that are likely to represent the very close progenitors of the outbreak strain. Mycobacterial interspersed repetitive units-variable number of tandem repeats typing and sequential accumulation of rifampicin resistance-associated rpoB mutations further confirmed the identity of the outbreak's progenitor strains. CONCLUSIONS. The data of the current study show that the progenitors of an MDR-TB outbreak strain could re-emerge among post-outbreak TB cases. We provide an IS6110 insertion site-based approach to better trace back the events preceding the emergence of MDR-TB outbreaks, irrespective of the availability of a pre-outbreak strain collection.

Re‐emergence of the Progenitors of a Multidrug‐Resistant Outbreak Strain ofMycobacterium tuberculosisamong the Post‐Outbreak Case Patients