Serial testing with an interferon-γ release assay in German healthcare workers

Aim: Data concerning conversion and reversion rates in the serial testing of healthcare workers (HCWs) is rare. So far, there is no consensus on how to define and interpret interferon-gamma release assays (IGRA) conversions and reversions, or how to deal with such results. We analysed conversion and reversion rates in the serial testing of HCWs using an IGRA. Methods: The study population comprises 287 HCWs, who participated in routine occupational safety and health screening for latent tuberculosis infection (LTBI) with the QuantiFERON-TB(®) Gold In-Tube assay (QFT). Four different definitions for conversion and reversion were applied: 1) transgression or regression above/below the cut-off; 2) increase from <0.2 to >0.7 IU/ml or decrease from >0.7 to <0.2 IU/ml; 3) transgression or regression above/below the cut-off plus change of ≥0.50 IU/ml; and 4) transgression or regression above/below the cut-off plus change of ≥0.70 IU/ml. Results: The highest conversion and reversion rates of 6.1% (95% CI 3.5 to 9.9) and 32.6% (95% CI 19.1 to 48.5) respectively were observed with the least stringent definition of negative to positive. The most stringent definition of an increase of ≥0.7 IU/ml above the cut-point produced the lowest conversion rate of 2.5% (95% CI 0.9 to 5.3). Using an uncertainty zone from 0.2 to 0.7 IU/ml gave low conversion (2.6%) and reversion rates (15.4%). Conclusion: Our data confirmed the findings of previous studies that suggest that a simplistic dichotomous negative to positive definition of the IGRA might be deceptive because of the high number of spontaneous conversions and reversions. Therefore using an uncertainty zone around the cut-point (e.g. 0.2 to 0.7 IU/ml) could improve the discrimination between unspecific variation around the diagnostic cut-off and true conversion or reversion.