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Published ahead of print on February 14, 2008, doi:10.1164/rccm.200711-1613OC

Am. J. Respir. Crit. Care Med., Volume 177, Number 10, May 2008, 1164-1170

A more recent version of this article appeared on May 15, 2008
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Submitted on November 1, 2007
Accepted on February 14, 2008

Predictive Value of a Whole-blood IFN-{gamma} Assay for the Development of Active TB Disease

Roland Diel1*, Robert Loddenkemper2, Karen Meywald-Walter3, Stefan Niemann4, and Albert Nienhaus5

1 School of Public Health, University of Duesseldorf, Duesseldorf, Germany, 2 Lungenklinik Heckeshorn, HELIOS Klinikum Emil von Behring, German Central Committee against Tuberculosis, Berlin, Germany, 3 Public Health Department Hamburg-Mitte, Hamburg, Germany, 4 Research Center Borstel, National Reference Center for Mycobacteria, Borstel, Germany, 5 Institution for Statutory Accident Insurance and Prevention in the Health and Welfare Services, Hamburg, Germany

* To whom correspondence should be addressed. E-mail: Roland.Diel{at}uni-duesseldorf.de.

Rationale: Numerous studies have been published on the new Mycobacterium tuberculosis (MTB) specific IFN-{gamma} release assays. However, their prognostic value for progression from latent tuberculosis infection (LTBI) to active tuberculosis (TB) has yet to be established. Objective: To compare the QuantiFERON-TB-Gold In Tube assay (QFT) with the tuberculin skin test (TST) in recently exposed close contacts of active TB cases with respect to their development of TB disease within 2 years. Methods: Close contacts, 601, of MTB-positive source cases underwent both TST and QFT testing and were subsequently observed for 103 (±13.5) weeks. Risk factors for MTB infection were evaluated by multivariate analysis. Results: For the TST, 40.4% (243/601) were positive at a 5mm cut-off, while only 66 (11%) were QFT positive. QFT positivity, but not TST, was associated with exposure time (p < 0.0001). Six contacts progressed to TB disease within the two year follow-up and all 6 were from a QFT positive group which had declined preventive treatment (n=41), equating to a progression rate of 14.6% (6/41) among those QFT positive. The progression rate for TST-positives was only 2.3% (5 of 219) and one subject who progressed was TST negative. Conclusions: Results suggest QFT screening determines more accurately than TST the presence of LTBI with at least equivalent sensitivity for predicting progression to TB. The high rate of progression to active TB of those QFT positive (14.6%), far greater than the 2.3% found for those TST positive, has significant health and economic implications for enhanced TB control.
Key words: tuberculosis; latent infection; IGRA; QuantiFERON; tuberculin skin test




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