Serial testing of health care workers for tuberculosis using interferon-γ assay

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/mI, and 11/147 participants (7.5%; 95% CI = 3.8-13.0) using IFN-gamma greater than or equal to 0.70 IU/mI. 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.