title: Re-emergence of the progenitors of a multidrug-resistant outbreak strain of Mycobacterium tuberculosis among the post-outbreak case patients.
abstract: 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.
authors.affiliation: Unit of Typing and Genetics of Mycobacteria, Institut Pasteur de Tunis, Tunis-Belvédère, Tunisie.
authors.forename: Amine
authors.initials: A
authors.lastname: Namouchi
authors.forename: Raja
authors.initials: R
authors.lastname: Haltiti
authors.forename: Dorra
authors.initials: D
authors.lastname: Hawari
authors.forename: Helmi
authors.initials: H
authors.lastname: Mardassi
mesh_terms: D004196:Disease Outbreaks; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D005838:Genotype; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics*; D018088:Tuberculosis, Multidrug-Resistant / Q000453:epidemiology* / Q000382:microbiology*; D014416:Tunisia / Q000453:epidemiology