Evaluation of quantitative IFN-gamma response for risk stratification of active tuberculosis suspects.
BACKGROUND
The contribution of interferon-gamma release assays (IGRAs) to appropriate risk stratification of active tuberculosis suspects has not been studied.


OBJECTIVE
To determine whether the addition of quantitative IGRA results to a prediction model incorporating clinical criteria improves risk stratification of smear-negative-tuberculosis suspects.


METHODS
Clinical data from tuberculosis suspects evaluated by the San Francisco Department of Public Health Tuberculosis Control Clinic from March 2005 to February 2008 were reviewed. We excluded tuberculosis suspects who were acid fast-bacilli smear-positive, HIV-infected, or under 10 years of age. We developed a clinical prediction model for culture-positive disease and examined the benefit of adding quantitative interferon (IFN)-gamma results measured by QuantiFERON-TB Gold (Cellestis, Carnegie, Australia).


RESULTS
Of 660 patients meeting eligibility criteria, 65 (10%) had culture-proven tuberculosis. The odds of active tuberculosis increased by 7% (95% confidence interval [CI], 3-11%) for each doubling of IFN-gamma level. The addition of quantitative IFN-gamma results to objective clinical data significantly improved model performance (c-statistic 0.71 vs. 0.78; P < 0.001) and correctly reclassified 32% of tuberculosis suspects (95% CI,11-52%; P < 0.001) into higher-risk or lower-risk categories. However, quantitative IFN-gamma results did not significantly improve appropriate risk reclassification beyond that provided by clinician assessment of risk (4%; 95% CI, -7 to +22%; P = 0.14).


CONCLUSIONS
Higher quantitative IFN-gamma results were associated with active tuberculosis, and added clinical value to a prediction model incorporating conventional risk factors. Although this benefit may be attenuated within highly experienced centers, the predictive accuracy of quantitative IFN-gamma levels should be evaluated in other settings.
San Francisco General Hospital, University of California, 94110-0111, USA. john.metcalfe@ucsf.edu
John Z
JZ
Metcalfe
Adithya
A
Cattamanchi
Eric
E
Vittinghoff
Christine
C
Ho
Jennifer
J
Grinsdale
Philip C
PC
Hopewell
L Masae
LM
Kawamura
Payam
P
Nahid
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D014376:Tuberculosis / Q000175:diagnosis* / Q000276:immunology
D007371:Interferon-gamma