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Increased risk for tuberculosis (TB) disease has been identified in foreign-born persons in the United States, particularly during the first 5 years after their arrival in the United States. This could be explained by undetected TB disease at entry, increased prevalence of latent TB infection (LTBI), increased progression from LTBI to TB, or a combination of these factors.We performed a cluster analysis of TB cases in Boston and a case-control study of risk factors for TB with an unclustered isolate among Boston residents with LTBI to determine whether such persons have an increased risk for reactivation of disease.Of 321 case patients with TB seen between 1996 and 2000, 133 isolates were clustered and 188 were not. In multivariate analysis, foreign birth was associated with an unclustered isolate (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.2 to 3.8; p0.01), while being a close contact of a TB case was negatively associated (OR, 0.22; 95% CI, 0.07 to 0.73; p = 0.02). When 188 TB patients with unclustered isolates were compared to 188 age-matched control subjects with LTBI, there was no association between the occurrence of TB and foreign birth (OR, 0.71; 95% CI, 0.42 to 1.3); among foreign-born persons, there was no association between the occurrence of TB and being in the United Statesor= 5 years (OR, 0.90; 95% CI, 0.56 to 1.44).We conclude that the increased risk for TB among foreign-born persons in the United States may be attributable to the increased prevalence of LTBI among foreign-born persons or the increased prevalence of active disease at arrival in the United States, but not to an increased rate of reactivation among persons with LTBI.