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Published ahead of print on May 11, 2006, doi:10.1164/rccm.200604-472OC
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American Journal of Respiratory and Critical Care Medicine Vol 174. pp. 349-355, (2006)
© 2006 American Thoracic Society
doi: 10.1164/rccm.200604-472OC

Original Article

Serial Testing of Health Care Workers for Tuberculosis Using Interferon-{gamma} Assay

Madhukar Pai, Rajnish Joshi, Sandeep Dogra, Deepak K. Mendiratta, Pratibha Narang, Shriprakash Kalantri, Arthur L. Reingold, John M. Colford, Jr., Lee W. Riley and Dick Menzies

Divisions of Epidemiology and Infectious Diseases, School of Public Health, University of California, Berkeley; Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California, San Francisco, California; Departments of Medicine and Microbiology, Mahatma Gandhi Institute of Medical Sciences, Sevagram, India; and the Montreal Chest Institute, McGill University, Montreal, Quebec, Canada

Correspondence and requests for reprints should be addressed to Madhukar Pai, M.D., Ph.D., McGill University, Department of Epidemiology, Biostatistics & Occupational Health, 1020 Pine Avenue West, Montreal, Canada H3A 1A2. E-mail: madhukar.pai{at}mcgill.ca

Rationale: Although interferon-{gamma} (IFN-{gamma}) assays are promising alternatives to the tuberculin skin test (TST), their serial testing performance is unknown.

Objective: To compare TST and IFN-{gamma} conversions and reversions in healthcare workers.

Methods: We prospectively followed-up 216 medical and nursing students in India who underwent baseline and repeat testing (after 18 mo) with TST and QuantiFERON-TB Gold In-Tube (QFT). TST conversions were defined as reactions greater than or equal to 10 mm, with increments of 6 or 10 mm over baseline. QFT conversions were defined as baseline IFN-{gamma} less than 0.35 and follow-up IFN-{gamma} greater than or equal to 0.35 or 0.70 IU/ml. QFT reversions were defined as baseline IFN-{gamma} greater than or equal to 0.35 and follow-up IFN-{gamma} less than 0.35 IU/ml.

Results: Of the 216 participants, 48 (22%) were TST-positive, and 38 (18%) were QFT-positive at baseline. Among 147 participants with concordant baseline negative results, TST conversions occurred in 14 (9.5%; 95% confidence interval [CI] = 5.3–15.5) using the 6 mm increment definition, and 6 (4.1%; 95% CI = 1.5–8.7) using the 10 mm increment definition. QFT conversions occurred in 17/147 participants (11.6%; 95% CI = 6.9–17.9) using the definition of IFN-{gamma} greater than or equal to 0.35 IU/ml, and 11/147 participants (7.5%; 95% CI = 3.8–13.0) using IFN-{gamma} greater than or equal to 0.70 IU/ml. Agreement between TST (10 mm increment) and QFT conversions (>= 0.70 IU/ml) was 96% ({kappa} = 0.70). QFT reversions occurred in 2/28 participants (7%) with baseline concordant positive results, as compared with 7/10 participants (70%) with baseline discordant results (p < 0.001).

Conclusions: IFN-{gamma} assay shows promise for serial testing, but repeat results need to be interpreted carefully. To meaningfully interpret serial results, the optimal thresholds to distinguish new infections from nonspecific variations must be determined.

Key Words: health care workers • interferon-{gamma} assay • serial testing • tuberculin skin test • tuberculosis




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