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Testing for latent tuberculosis
Submit responseTesting for latent tuberculosis remains fishing in muddy water. In the systematic review of Pai and coworkers (1) on interferon-based tests, two points merit emphasis. First, sensitivity and specificity characterise tests, but do little to inform patient care. Interpretation of tests for individual patients requires knowledge of disease prevalence, and of the predicitive values of the test. The systematic review (1) neither formally tested the statistical significance of the differing test characteristics (sensitivity, specificity), nor could it report the tests' predicitive values. This directly leads to point two: lack of a well-defined reference standard. The authors choose 'active tuberculosis' as a surrogate. For latent tuberculosis, the essential questions are 1) What is the probability, that this patient will develop tuberculosis? and 2) What is the probability, that this patient will benefit from treatment? Defining the incidence of active tuberculosis, depending on test results, requires studies with appropriate follow-up (2) and stratification by pre-test probabilities (3). 1. Pai M, Zwerling A, Menzies D. Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update. Ann Intern Med. 2008; 149: [PMID: 18593687] 2. Diel R, Loddenkemper R, Meywald-Walter K, Niemann S, Nienhaus A. Predictive value of a whole blood IFN-gamma assay for the development of active tuberculosis disease after recent infection with Mycobacterium tuberculosis. Am J Respir Crit Care Med. 2008; 177: 1164-70. [PMID:18276940] 3. Horsburgh CR Jr. Priorities for the treatment of latent tuberculosis infection in the United States. N Engl J Med. 2004; 350: 2060-7. [PMID: 15141044] Conflict of Interest:None declared
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TB or Not TB: That is the Question
Submit responseTo the editor, We would like to commend the authors on their comprehensive meta-analysis which leads to the conclusion that interferon gamma release assays have promise in detecting false positive tuberculin skin tests in the BCG vaccinated population. In rheumatology we are treating an immunosuppressed patient population using novel therapeutics such as the anti-TNF agents which carry a significant risk of TB reactivation causing both an increased morbidity and mortality. At our institution where the population is high with BCG vaccinated and AFB exposed patients, we have discovered significant discordance between the interferon gamma release ELISA assay (T-SPOT). Because there is no clear gold standard for a diagnosis of latent tuberculosis infection, it is difficult to establish the significance of this data. However, of the data that was gathered, there are key points to be gleaned. First, of the patients evaluated for TB exposure, nearly 20 percent did not follow-up for tuberculin skin test reading. Second, one of our lupus patients with a negative tuberculin skin test (anergic to candida control) with a positive T-SPOT analysis developed military tuberculosis. The sensitivity of these assays is in question, as well as the inability to differentiate between latent tuberculosis and active tuberculosis infection. However, the utility of this test may lie in different scenarios. As previously mentioned, the IGRA tests may help distinguish false positive TST skin tests in patients inoculated with the BCG vaccine. In addition, the test may prove to be beneficial in false negative TST skin tests, which is common in immunosuppressed patients. Finally, the blood test is much less operator dependent and does not depend on patient adherence to follow-up or to chart documentation of skin test and controls. As we enter an era of innovative strategies that target specific areas of the immune system such as TNF, the importance of TB detection cannot be overemphasized. Conflict of Interest:None declared