Submitted on June 30, 2009
Accepted on September 30, 2009
Evaluation of Quantitative Interferon-
Response for Risk Stratification of Active Tuberculosis Suspects
John Z Metcalfe1*, Adithya Cattamanchi2, Eric Vittinghoff3, Christine Ho4, Jennifer Grinsdale5, Philip C Hopewell6, L. Masae Kawamura5, and Payam Nahid6
1 Division of Pulmonary and Critical Care Medicine, University of California, San Francisco at San Francisco General Hospital, San Francisco, California, United States,
2 Division of Pulmonary and Critical Care Medicine, University of California, San Francisco at San Francisco General Hospital, California, United States,
3 Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, United States,
4 Tuberculosis Control Section, Department of Public Health and, Centers for Disease Control and Prevention, San Francisco, California, United States,
5 Tuberculosis Control Section, Department of Public Health, San Francisco, California, United States,
6 Division of Pulmonary and Critical Care Medicine, University of California, San Francisco at San Francisco General Hospital and, Tuberculosis Control Section, Department of Public Health, San Francisco, CA, United States
* To whom correspondence should be addressed. 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.
Objective: To determine whether 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- results measured by QuantiFERON®-TB Gold.
Main Results: Of 660 patients meeting eligibility criteria, 65 (10%) had culture-proven tuberculosis. The odds of active tuberculosis increased by 7% (95% CI 3-11%) for each doubling of interferon- level. The addition of quantitative interferon- 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 or lower risk categories. However, quantitative interferon- results did not significantly improve appropriate risk reclassification beyond that provided by clinician assessment of risk (5%, 95% CI -7 to +22%, p=0.14).
Conclusion: Higher quantitative interferon- results were associated with active tuberculosis, and added clinical value to a prediction model incorporating conventional risk factors. While this benefit may be attenuated within highly experienced centers, the predictive accuracy of quantitative interferon- levels should be evaluated in other settings.
Key words: Interferon-gamma release assay •
Quantiferon •
risk prediction •
risk reclassification
