Abstract
BackgroundAlthough the tuberculin skin test (TST) is frequently used to aid in the diagnosis of tuberculosis (TB) disease and to identify persons with latent TB infection, it is an imperfect test and approximately 10–25% of persons with microbiologically confirmed TB disease have a negative TST. Previous studies have suggested that persons with a negative TST are more likely to present with severe TB disease and have an increased rate of TB-related death.MethodsWe analyzed culture-confirmed TB cases captured in US TB surveillance data from 1993 to 2008 and performed multivariate logistic regression analysis to determine the association between TST result and death.ResultsOf 284,866 cases of TB reported in the US, 58,180 persons were eligible for inclusion in the analysis and 3,270 of those persons died after initiating TB treatment. Persons with a negative TST accounted for only 14% of the eligible cases but accounted for 42% of the deaths. Persons with a TST≥15 mm had 67% lower odds of death than persons with a negative TST (adjusted odds ratio 0.33, 95% confidence interval 0.30–0.36).ConclusionsA negative TST is associated with an increased risk of death among persons with culture-confirmed TB disease, even after adjustment for HIV status, site of TB disease, sputum smear AFB status, drug susceptibility, age, sex, and origin of birth. In addition to indicating risk of developing disease, the TST may also be a marker for increased risk of death.
Highlights
Since its introduction in 1890 the tuberculin skin test (TST) has been widely adopted to test for infection with Mycobacterium tuberculosis complex (MTBC), both to aid in the diagnosis of tuberculosis disease and to identify individuals with latent tuberculosis infection who might benefit from treatment to prevent progression to TB disease. [1,2] A positive TST result is based on measurable skin induration in response to intradermally injected purified protein derivative antigens and relies on memory cell immune responses to mycobacterial antigens
Approximately 10–25% of patients with microbiologically confirmed, active TB disease do not respond to tuberculin and have a negative TST result. [1,3,4] in these individuals the negative TST result does not correspond to microbiologically confirmed M. tuberculosis infection
Previous studies have shown that adults with active TB and a negative TST are more likely to have disseminated disease or pulmonary disease with severe illness. [1,5,6] young children, people with HIV infection, and people with other immunocompromising conditions such as malnutrition with active TB are more likely to present with disseminated disease and are more likely to have a negative TST when compared with immunocompetent adults. [7,8,9] Children and people with HIV with a negative TST in the setting of active TB have been shown to have an increased risk of TB-related death in small cohort studies. [10,11] We are not aware of any studies that report an association between a negative TST and death among other patient populations
Summary
From 1993 through 2008, there were 284,866 cases of tuberculosis reported in the United States of which 251,366 either completed therapy or died. People with HIV infection, US-born persons, persons older than 65 years, and those with smear-negative, extrapulmonary, or miliary disease were less likely to have a TST result reported and less likely to be included in the analysis (Table 1). An increased odds of death was found in persons older than 45 years, persons with HIV infection or unknown HIV status, US-born persons, and those with disseminated, AFB smear-positive, or drug-resistant disease. Inclusion of all persons with a documented TST result regardless of culture result (e.g., including cases diagnosed clinically) did not appreciably alter the results of the analysis (n = 145,108:5–9 mm aOR 0.47, 95% CI 0.40–0.54; 10–14 mm aOR 0.36, 95% CI 0.34– 0.39; $15 mm aOR 0.28, 95% CI 0.26–0.30)
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