Predictive value of a whole blood IFN-gamma assay for the development of active tuberculosis disease after recent infection with Mycobacterium tuberculosis.
BACKGROUND
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 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 (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.


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.
Diel
Roland
R
School of Public Health c/o Institute of Medical Sociology, University of Düsseldorf, Postbox 101007, 40001 Düsseldorf, Germany. roland.diel@uni-duesseldorf.de
Loddenkemper
Robert
R
Meywald-Walter
Karen
K
Niemann
Stefan
S
Nienhaus
Albert
A
D000293:Adolescent; D000328:Adult; D002353:Carrier State / Q000175:diagnosis*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D016358:Contact Tracing; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005858:Germany; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000032:analysis*; D008297:Male; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D009163:Mycobacterium bovis; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D014374:Tuberculin Test; D014376:Tuberculosis / Q000175:diagnosis* / Q000276:immunology / Q000635:transmission
D007371:Interferon-gamma