The demographic characteristics of the population of Madrid, with a steady increase in immigrants, from 4.7% in 1998 to 17.4% in 2007, provide an opportunity to study in depth the transmission of TB. Our aim was to compare two 3-year longitudinal molecular studies of TB to define transmission patterns and predictors of clustering. Two prospective population-based molecular and epidemiological studies (2002-2004 and 2005-2007) of TB patients were conducted in nine urban districts in Madrid using the same methodology. During the period 2002-2007, 2248 cases of TB were reported, and the incidence decreased from 23.5 per 100,000 in 2002 to 20.8 in 2007 (p <0.001). A total of 1269 isolates were molecularly characterized and included in the study. The comparison between the two periods showed that the percentage of foreign-born patients among TB cases increased from 36.2% to 45.7% (p <0.001). Furthermore, the percentage of clustered cases decreased (36.6% vs. 30.6%; p 0.028), and this decline was associated with a decrease of clustered cases among men and people under 35 years. We also observed a decrease in cases belonging to clusters containing ≥ 6 people (14.2% vs. 8.2%; p <0.001), and in cases belonging to mixed clusters containing Spanish-born and foreign-born patients (18.5% vs. 11.1%, p <0.001). Our molecular epidemiology study provides clues to interpret the decrease in the incidence of TB in a context of steady increase of immigration. In our region, the decrease in the incidence of TB can be explained predominantly as a result of a decline in recent transmission.

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