摘要：Objectives. We compared mortality among tuberculosis (TB) survivors and a similar population. Methods. We used local health authority records from 3 US sites to identify 3853 persons who completed adequate treatment of TB and 7282 individuals diagnosed with latent TB infection 1993 to 2002. We then retrospectively observed mortality after 6 to 16 years of observation. We ascertained vital status as of December 31, 2008, using the Centers for Disease Control and Prevention’s National Death Index. We analyzed mortality rates, hazards, and associations using Cox regression. Results. We traced 11 135 individuals over 119 772 person-years of observation. We found more all-cause deaths (20.7% vs 3.1%) among posttreatment TB patients than among the comparison group, an adjusted average excess of 7.6 deaths per 1000 person-years (8.8 vs 1.2; P < .001). Mortality among posttreatment TB patients varied with observable factors such as race, site of disease, HIV status, and birth country. Conclusions. Fully treated TB is still associated with substantial mortality risk. Cure as currently understood may be insufficient protection against TB-associated mortality in the years after treatment, and TB prevention may be a valuable opportunity to modify this risk. Elimination of tuberculosis (TB) is an important facet of public health policy in the United States. 1–4 Coordinated and deliberate efforts have steadily decreased TB incidence and mortality to historically low levels: in 2010, 11 163 new domestic TB cases were reported and 320 (2.9%) died from TB-attributable causes before or during treatment; treatment was successfully completed for more than 88.0% of persons for whom an initial drug regimen was prescribed. 5 But meeting the goals of domestic TB elimination will require more than finding and treating TB disease. Substantial reservoirs of latent TB infection (LTBI) exist within the United States; in 1999–2000, projections from the National Health and Nutrition Examination Survey (NHANES) estimated that 11.2 million individuals, two thirds of them foreign-born, had LTBI. 6 These numbers are continuously augmented by global immigration and by transmission from persons with TB. Because treatment levels of TB disease are already very high in the United States, further progress toward elimination will depend largely on prevention through LTBI diagnosis and treatment or other means. 7 LTBI is frequently found through screening in developed countries, but treatment decisions are often conservative because of diagnostic, clinical, and other factors, and prevention policy and practice in this population is inconsistent. 8–13 Generally, LTBI treatment is recommended only for persons at high risk for developing TB. 9 These recommendations are grounded partly on cost-effectiveness analyses and clinical considerations of health risks and benefits that include estimates of TB deaths prevented by LTBI treatment. These estimates usually refer only to deaths associated with acute-phase TB disease; some models explicitly assume that survivors of TB disease experience no long-term morbidity. 14 If these assumptions are incorrect and survivors of TB experience significant long-term morbidity or mortality because of TB, LTBI treatment is undervalued, with important consequences for policy and prevention. Indeed, there is growing evidence of persistent health deficits in some TB patients after successful treatment completion, including permanent anatomical changes in the lungs and other affected organs that could elevate long-term mortality risk. 15–27 For example, fewer than 40% of patients with a history of meningeal TB and no reported lung involvement remained alive 45 months after completing therapy. 28 Still, long-term survival and mortality risks among patients who complete TB treatment remain unclear. Evidence of increased mortality among patients considered cured of TB has substantial potential utility. Such evidence, especially when associated with sequelae of acute TB disease, would suggest prevention has value not reflected in current practice. In addition, descriptions of the distribution of mortality risk by readily observable factors would allow more careful targeting of prevention efforts. We hypothesized that persons who complete adequate therapy for TB disease are at increased risk of subsequent all-cause mortality. We tested this hypothesis using a retrospective comparison of mortality rates and risks of fully treated TB survivors and a comparison group with LTBI but no history of TB disease. We analyzed all-cause mortality after TB cure to identify disproportionate mortality as a potentially modifiable risk factor.
