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Evaluation of Quantitative IFN- Response for Risk Stratification of Active Tuberculosis Suspects

¹ Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, and ² Department of Epidemiology and Biostatistics, University of California, San Francisco; ³ Tuberculosis Control Section, Department of Public Health; and ⁴ Centers for Disease Control and Prevention, San Francisco, California

Correspondence and requests for reprints should be addressed to John Z. Metcalfe, M.D., M.P.H., University of California, San Francisco Division of Pulmonary and Critical Care Medicine, 1001 Potrero Avenue, Rm 5K1, San Francisco, CA 94110-0111. E-mail: john.metcalfe{at}ucsf.edu

Rationale: The contribution of interferon- release assays (IGRAs) to appropriate risk stratification of active tuberculosis suspects has not been studied.

Objectives: 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)- results measured by QuantiFERON-TB Gold (Cellestis, Carnegie, Australia).

Measurements and Main 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- level. The addition of quantitative IFN- 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- 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- 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- levels should be evaluated in other settings.

Key Words: interferon-gamma release assay • Quantiferon • risk prediction • risk reclassification

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject The role of interferon- release assays (IGRAs) in the evaluation of active tuberculosis suspects is controversial. To date, whether IGRAs improve classification of smear negative tuberculosis suspects into clinically relevant risk categories has not been examined. What This Study Adds to the Field Quantitative interferon- levels measured by QuantiFERON-TB Gold improves risk stratification of smear-negative active tuberculosis suspects when added to objective clinical and demographic risk factors. However, this benefit is attenuated when the judgment of experienced clinicians is also considered.