© 2008 American Thoracic Society
Is the Whole-Blood Gamma Interferon Assay Better than the Tuberculin Skin Test in Predicting Active Tuberculosis?From the Authors:Commenting on our article (1), Dr. Leung and colleagues suggest that social inequity in the Hamburg region may affect health outcomes in relation to tuberculosis (TB) progression. However, we referred those subjects of our study who were found to be QuantiFeron-TB-Gold In-Tube Assay (QFT) positive to local pneumonologists. Those private physicians were not affiliated with our study group. The decision to offer isoniazid (INH) chemoprevention or not was made after review of all available information, and acceptance was absolutely voluntary. Unsurprisingly, more subjects of foreign ethnicity—although German born—developed TB disease, but place of birth was not a significant determinant variable among subjects for acceptance of INH treatment. With regard to our results on the predictive power of the QFT for recent TB contacts progressing to active TB (1), Leung and coworkers suggest that a tuberculin skin test (TST) cutoff of >5 mm for contacts of patients with active TB may be inappropriate. The study was conducted in Germany and published in the United States, countries where 5 mm is the recommended cutoff in contact investigations, regardless of bacillus Calmette-Guérin (BCG) status, as it is in many industrialized nations. Since conventions for TST cutoffs vary around the world, we discussed the effect on our results of placing TST cutoffs at 10 and 15 mm (1). Use of higher TST cutoffs occur generally where BCG revaccination has been common or where BCG is given after 2 years of age—and the cost is reduced TST sensitivity (2). Guidelines using 5 mm as a cutoff in contact investigations represent the summation of many decades of international analysis showing that TB progression occurs in those with reactions below 10 and 15 mm. Leung and coworkers note this point in their letter, which reports on an extensive study on TST induration size and TB outcome in 94,928 mostly BCG vaccinated children (3). In that study, TST sensitivity is 54% at 10 mm, and 39% at 15 mm. Other studies show similar outcomes (4, 5). Assuming that accurate vaccination status can be ascertained in each and every subject, the higher predictive capacity of limited (higher) TST cutoff pays, in our view, an unacceptably high price in terms of lost sensitivity (6). The primary reason that many TB control programs use a 5-mm cutoff in high-risk individuals is to obtain higher sensitivity. While the aggregate numbers of subjects allow statistical analysis of the QFT results, in our study only one of six subjects who developed TB had a TST reaction of less than 10 mm, and it was, in fact, even below 5 mm. Therefore, it must be underscored that the data in our study on TST reactions below 10 mm are very limited.
University of Düsseldorf FOOTNOTES Conflict of Interest Statement: R.D. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
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assay for the development of active tuberculosis disease after recent infection with Mycobacterium tuberculosis. Am J Respir Crit Care Med 2008;177:1164–1170.