title: Widespread pyrazinamide-resistant Mycobacterium tuberculosis family in a low-incidence setting.
abstract: An unusually high prevalence of pyrazinamide (PZA) monoresistance in Mycobacterium tuberculosis has been observed in Quebec. In the absence of a recognized outbreak, we hypothesized that these isolates most likely represented reactivation of an old endemic strain in this low-incidence area. A case-control study of 77 PZA-resistant isolates with a specific Quebec mutation and 253 PZA-susceptible control M. tuberculosis isolates was undertaken. By molecular analysis, all 77 case isolates shared a unique mutation profile in the pncA gene which was not present in control isolates. While control isolates manifested diverse IS6110 restriction fragment length polymorphism (RFLP) patterns, spoligotypes, and major genetic groups, case isolates had similar but nonidentical IS6110 RFLP patterns, had common spoligotypes, and were confined to one major genetic group, suggesting a common clonal ancestor. By epidemiologic and geographic analyses, however, there were no significant differences between the cases and the controls. We conclude that a clonally related family of PZA-monoresistant M. tuberculosis isolates in Quebec represents historic rather than recent transmission.
authors.affiliation: Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Dao
authors.initials: D
authors.lastname: Nguyen
authors.forename: Paul
authors.initials: P
authors.lastname: Brassard
authors.forename: Jennifer
authors.initials: J
authors.lastname: Westley
authors.forename: Louise
authors.initials: L
authors.lastname: Thibert
authors.forename: Melanie
authors.initials: M
authors.lastname: Proulx
authors.forename: Kevin
authors.initials: K
authors.lastname: Henry
authors.forename: Kevin
authors.initials: K
authors.lastname: Schwartzman
authors.forename: Dick
authors.initials: D
authors.lastname: Menzies
authors.forename: Marcel A
authors.initials: MA
authors.lastname: Behr
mesh_terms: D000581:Amidohydrolases / Q000235:genetics; D000995:Antitubercular Agents / Q000494:pharmacology*; D016022:Case-Control Studies; D004251:DNA Transposable Elements; D024881:Drug Resistance, Bacterial; D005838:Genotype; D006801:Humans; D015994:Incidence; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics; D009841:Oligonucleotides / Q000032:analysis; D012150:Polymorphism, Restriction Fragment Length; D011718:Pyrazinamide / Q000494:pharmacology*; D011792:Quebec / Q000453:epidemiology; D014397:Tuberculosis, Pulmonary / Q000453:epidemiology* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D004251:DNA Transposable Elements; D009841:Oligonucleotides; D011718:Pyrazinamide; D000581:Amidohydrolases; C022490:pyrazinamide deamidase