In low-incidence countries targeting tuberculosis (TB) elimination, TB remains a problem of a few high-risk groups. In Canada, Aboriginals, and particularly the Arctic Inuit communities, have witnessed dramatic decreases in TB during the 1960s to 1970s, but rates remain at least 10 to 20 times higher than the national average. We are describing the results of an integrated traditional and molecular epidemiology study of all culture-positive Mycobacterium tuberculosis cases in the Arctic Inuit communities of Quebec from 1990 until 2000. The demographic characteristics of the 46 TB cases included in the study were most notable for a bimodal age distribution (48% under 25 years). Genotyping analysis using multiple modalities (IS6110 restriction fragment length polymorphism, spoligotype, mycobacterial interspersed repetitive units-variable number tandem repeats) showed that 76% (35/46) of TB cases were clustered (six clusters, median size four cases) and estimated that at least 62.5% of TB cases were due to ongoing transmission. By integrating the epidemiologic and genotyping data, we observed that the genotyping clustering results were concordant with recognized epidemiologic links but most notably identified previously unrecognized intervillage transmission. This study demonstrates significant ongoing transmission in a geographically isolated, low-density population. In a resource-rich country such as Canada, these communities illustrate some of the persistent challenges of TB control and elimination.

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 PZAresistant 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 PZAmonoresistant M. tuberculosis isolates in Quebec represents historic rather than recent transmission.

Population-based studies have used DNA typing of Mycobacterium tuberculosis organisms to estimate the extent of ongoing tuberculosis transmission in various communities and to characterize associated risk factors. The finding of matched DNA "fingerprints" among isolates from an immigrant subgroup may reflect transmission in the adopted country but could also reflect limited diversity among M. tuberculosis organisms within that immigrant community. The authors sought to determine which hypothesis is more likely to explain the high frequency of matched isolates among Haitian-born tuberculosis patients in Montreal, Quebec, Canada. The authors determined the number of different bacterial genotypes in this community as compared with other foreign-born tuberculosis patients and applied a recently described measure of genetic similarity between M. tuberculosis organisms ("genetic distance"). Among 76 Haitian-born tuberculosis patients diagnosed during 1996-1998, the authors identified 47 distinct genotypes on the basis of standard IS6110 DNA typing and categorical analysis. In genetic distance analysis, these 47 genotypes showed as great a genetic diversity as that observed among the 191 distinct genotypes identified in 216 other foreign-born tuberculosis patients. A mycobacterial "founder effect" is unlikely to account for the high proportion of shared isolates among Haitian-born Montrealers. Recent transmission remains the most likely explanation.