Exogenous Reinfection as a Cause of Late Recurrent Tuberculosis in the United States

Rationale: The etiology of recurrent tuberculosis is typically presumed to be reactivation of residual Mycobacterium tuberculosis infection, but reinfection may account for a greater proportion of recurrent tuberculosis than previously recognized. Objective: To use M. tuberculosis genotyping to characterize the etiology of recurrent tuberculosis occurring 12 months or more after treatment completion. Methods: The study population for this national population-based cohort was drawn from the estimated 3,039 persons reported to the National Tuberculosis Surveillance System with two episodes of tuberculosis in the United States during 1993-2011, 194 of whom had genotyping results from both the initial and subsequent episode. We analyzed the proportion of recurrent tuberculosis attributable to and risk factors associated with reinfection. Measurements and Main Results: Among 136 recurrences meeting inclusion criteria, genotypes between episodes were the same for 116 (85%) recurrences during 1996-2011; the 20 (15%) with differing genotypes were categorized as reinfections. Using exact logistic regression, factors associated with reinfection included Mexican birth with both TB episodes diagnosed in the United States within 12 years of immigration (adjusted odds ratio, 10.7; 95% confidence interval, 1.7-86.3) and exclusive use of directly observed therapy for treatment of the first episode (adjusted odds ratio, 4.5; 95% confidence interval, 1.0-29.2). Conclusions: Reinfection was the cause of 15% of late recurrent tuberculosis cases in this U.S. cohort. The proportion caused by reinfection increased to 60% in certain subpopulations, such as recent immigrants from Mexico, suggesting that, despite successful treatment for tuberculosis during their first episode, these individuals remain in a social environment where they are reexposed to M. tuberculosis. Public health interventions to prevent novel reinfection might require a broader focus in these communities.