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Background The metropolitan area of Bologna, a city in Northern Italy (Emilia Romagna region), is considered a low incidence setting for TB, but has a high rate of foreign immigration (13.5% official resident immigrants relative to the whole population in 2011). The aim of this study was to describe the epidemiological trend of TB, focusing on differences between Italian and foreign-born cases. Methods We examined all bacteriologically confirmed TB cases identified in the Microbiology Unit of Bologna University Hospital from January 2008 and December 2011. We compared demographic, clinical and microbiological data for Italian vs. foreign-born TB cases. Results Out of 255 TB cases identified during the study period, 168 (65.9%) were represented by foreign-born cases. The proportion of immigrants with TB progressively increased over the study period (from 60.8% in 2008 to 67.5% in 2011). Although foreign-born cases were significantly younger than Italian cases (mean age 32.3±14.4 years vs 61.9±21.5 years), the mean age among the latter decreased from 71.2 in 2008 to 54.6 years in 2011 (p=0.036). Concerning TB localization, 65.9% (n=168) had pulmonary TB (P-TB) and 34.1% (n=87) extra-pulmonary TB (EP-TB). In this study, 35.6% of Italian-born P-TB cases were smear positive, versus 51.4% of foreign-born P-TB cases. The highest proportion of high-grade positive microscopy P-TB was among subjects between 25-34 years old (36.9%; p=0.004). Mono-resistance to isoniazid (mono-H) was found among 9.2% and 10.1% of Italian and foreign-born cases, respectively. Among Italian cases, resistance to H and any other first line drug (poly-H) and Multidrug resistant TB (MDR-TB) were 4.6% and 1.2%, respectively. In foreign-born cases poly-H (12.8%) and MDR-TB (6.9%) significantly increased over the time (p=0.003 and p=0.007, respectively). The proportion of MDR-TB was significantly higher among immigrants from Eastern Europe (10.9%) compared to Italian-born patients (p=0.043). All (n=9) MTB strains resistant to four or five first line drugs and Extensively drug resistant (XDR-TB) strains were from foreign-born cases. Conclusions TB epidemiology in a low incidence setting is strongly influenced by immigration rates. Ethnicity, mean age, and incidence of MDR-TB among foreign-born cases reflect immigration trends in Northern Italy. [ABSTRACT FROM AUTHOR]