© 2008 American Thoracic Society
Is the Whole-Blood Gamma Interferon Assay Better than the Tuberculin Skin Test in Predicting Active Tuberculosis?To the Editor:
We read with great interest the article by Dr. Diel and colleagues on the comparison between the QuantiFERON-TB-Gold In-Tube Assay (QFT) and the tuberculin skin test (TST), using development of active tuberculosis (TB) as the endpoint (1). While this is the first report establishing the prognostic value of the interferon- Previous reports suggested that BCG vaccination at infancy does not affect the interpretation of the TST in adults, using a 10-mm cutoff, but this might not apply for a lower cutoff, vaccination later on, or revaccination following initial inoculation in infancy (2, 3). The specificity for TST increases with higher cutoff points (4, 5). A 15-mm cutoff is routinely used for BCG-vaccinated subjects in other European populations (6), even though there might be concern over the trade-off in sensitivity (5). Using a 5-mm cutoff in the study by Diel and coworkers (1), the TST gave a poorer positive predictive value (PPV) for active TB than did the QFT, largely because of a much higher proportion of positive tests (40.4 vs. 11.0%), and there were clearly more positive TST results among vaccinated than unvaccinated subjects (67.3 vs. 17.3%, P < 0.001). Among unvaccinated contacts, there was no major difference in performance between the two tests. Positive QFT test results were significantly associated with foreign birth and increasing age, in addition to exposure time, thus ruling out better discrimination between recent and remote infection. Raising the TST cutoff to 10 mm decreased the overall positive rate to 29.1%, but maintained the sensitivity in predicting five out of six active TB cases. The difference in PPV between the TST and QFT would then become much smaller and fail to reach statistical significance with the available sample size. Further studies with larger samples are therefore warranted to establish the relative performance between the TST and QFT, both in populations with lower BCG coverage and when higher TST cutoffs are used. Of note, TB cases were found predominantly among local-born contacts in families of ethnic minorities in the above study (1). Only one of the new TB cases received BCG vaccination before and none was given preventive treatment despite a positive QFT/TST test. Social inequity could have existed, and this might need to be addressed to achieve better health care outcome.
Department of Health
Grantham Hospital FOOTNOTES Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
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release assay (IGRA), the choice of a 5-mm cutoff for bacillus Calmette-Guérin (BCG)–vaccinated contacts might have biased the comparison and undermined the value of the TST.