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Published ahead of print on May 11, 2006, doi:10.1164/rccm.200604-472OC

Am. J. Respir. Crit. Care Med., Volume 174, Number 3, August 2006, 349-355

A more recent version of this article appeared on August 1, 2006
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Submitted on April 3, 2006
Accepted on May 9, 2006

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

Madhukar Pai1*, Rajnish Joshi2, Sandeep Dogra3, Deepak K Mendiratta3, Pratibha Narang3, Shriprakash Kalantri3, Arthur L Reingold4, John M Colford, Jr.4, Lee W Riley4, and Dick Menzies5

1 Divisions of Epidemiology and Infectious Diseases, University of California, School of Public Health, Berkeley, CA, USA; Departments of Medicine and Microbiology, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Maharashtra, India; Division of Pulmonary and Critical Care Medicine, University of California, San Francisco General Hospital, San Francisco, CA, USA, 2 Divisions of Epidemiology and Infectious Diseases, University of California, School of Public Health, Berkeley, CA, USA; Departments of Medicine and Microbiology, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Maharashtra, India, 3 Departments of Medicine and Microbiology, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Maharashtra, India, 4 Divisions of Epidemiology and Infectious Diseases, University of California, School of Public Health, Berkeley, CA, USA, 5 McGill University, Montreal Chest Institute, Montreal, Quebec, Canada

* To whom correspondence should be addressed. E-mail: madhupai{at}berkeley.edu.

Rationale: Although interferon-{gamma} assays are promising alternatives to the tuberculin skin test (TST), their serial testing performance is unknown. Objective: To compare TST and interferon-{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 months) with TST and QuantiFERON-TB-Gold In-Tube (QFT). TST conversions were defined as reactions ≥10 mm, with increments of 6 or 10 mm over baseline. QFT conversions were defined as baseline interferon-{gamma} <0.35 and follow-up interferon-{gamma} ≥0.35 or ≥0.70 IU/mL. QFT reversions were defined as baseline interferon-{gamma} ≥0.35 and follow-up interferon-{gamma} <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% CI 5.3, 15.5) using the 6 mm increment, and 6 (4.1%; 95% CI 1.5, 8.7) using the 10 mm definition. QFT conversions occurred in 17/147 (11.6%; 95% CI 6.9, 17.9) using the definition of interferon-{gamma} ≥0.35 IU/mL, and 11/147 (7.5%; 95% CI 3.8, 13.0) using interferon-{gamma} ≥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 (7%) participants with baseline concordant positive results, as compared to 7/10 (70%) with baseline discordant results [P<0.001]. Conclusions: Interferon-{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 non-specific variations must be determined.
Key words: tuberculosis, interferon-gamma assay, tuberculin skin test, health care workers, serial testing




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