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Predictive Value of a Whole Blood IFN- Assay for the Development of Active Tuberculosis Disease after Recent Infection with Mycobacterium tuberculosis

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

Correspondence and requests for reprints should be addressed to Dr. Med. Roland Diel, Assistant Professor, School of Public Health c/o Institute of Medical Sociology, University of Düsseldorf, Postbox 101007, 40001 Düsseldorf, Germany. E-mail: roland.diel{at}uni-duesseldorf.de

Rationale: Numerous studies have been published on the new Mycobacterium tuberculosis (MTB)–specific IFN- release assays. However, their prognostic value for progression from latent tuberculosis infection (LTBI) to active TB has yet to be established.

Objectives: 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 (n = 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.

Measurements and Main Results: For the TST, 40.4% (243/601) of contacts were positive at a 5-mm cutoff, whereas 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 2-year follow-up. All were QFT positive and had declined preventive treatment, equating to a progression rate of 14.6% (6/41) among those who were QFT positive. The progression rate for untreated TST-positive subjects was significantly lower (P < 0.003), at 2.3% (5 of 219), and one subject who progressed was TST negative.

Conclusions: Results suggest that QFT is a more accurate indicator of the presence of LTBI than the TST and provides at least the same sensitivity for detecting those who will progress to active TB. The high rate of progression to active TB of those who are QFT positive (14.6%), which is far greater than the 2.3% found for those who are TST positive, has health and economic implications for enhanced TB control, particularly if this higher progression rate is seen in studies of other at-risk populations.

Key Words: tuberculosis • latent infection • IFN- release assay • predictive value • disease development

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject In contrast to IFN- release assay (IGRA) tests, the tuberculin skin test (TST) suffers from high rates of false-positive responses in contacts of active tuberculosis (TB) cases. However, the key question that remains unanswered is whether IGRAs are better than the TST in predicting the development of TB. What This Study Adds to the Field IGRA testing appears to be a more accurate indicator of the presence of latent TB infection than the TST and provides at least the same sensitivity for detecting individuals who will progress to active TB.

 

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