Discordant QuantiFERON-TB Gold Test Results Among US Healthcare Workers With Increased Risk of Latent Tuberculosis Infection: A Problem or Solution?

Abstract

OBJECTIVE In late 2006, our hospital implemented use of the QuantiFERON-TB Gold (QFT-G) assay, a whole-blood interferon-γ release assay, for detection of tuberculosis infection. All newly hired healthcare workers (HCWs) with positive Mantoux tuberculin skin test (TST) results were routinely tested with the QFT-G assay, to take advantage of its higher specificity. We then undertook a quality assurance review to evaluate the QFT-G test results in HCWs with multiple risk factors for latent tuberculosis infection (LTBI). METHODS The clinical records for TST-positive HCWs tested with the QFT-G assay were reviewed. HCWs with 2 or more risk factors commonly associated with LTBI were classified as “increased risk” (IR). IR HCWs who had negative QFT-G test results underwent repeat QFT-G testing and were offered testing with a different interferon-γ release assay (T-SPOT.TB) and with extended T cell stimulation assays. RESULTS Of 143 TST-positive HCWs tested with the QFT-G assay, 26 (18%) had positive results, 115 (81%) had negative results, and 2 (1%) had indeterminate results. Of 82 IR HCWs, 23 (28%) had positive QFT-G test results, and 57 (70%) had negative results. Of the 57 IR HCWs with negative results, 43 underwent repeat QFT-G testing: 41 had negative results again, and 2 had positive results. These 43 HCWs were also offered additional testing with the T-SPOT.TB diagnostic, and 36 consented: 31/36 tested negative, and 5/36 tested positive. Extended assays using the antigens ESAT-6 and CFP-10 confirmed the positive results detected by the overnight assays and yielded positive results for an additional 7/36 (19%) of individuals; strikingly, all 36 HCWs had strongly positive test results with assays using purified protein derivative. CONCLUSIONS The extreme discordance between the results of our clinical diagnostic algorithm and the results of QFT-G testing raises concern about the sensitivity of the QFT-G assay for detection of LTBI in our HCWs. Results of extended stimulation assays suggest that many of our IR HCWs have indeed been sensitized to Mycobacterium tuberculosis. It is possible that the QFT-G assay identifies those at higher reactivation risk rather than all previously infected, but, in the absence of long-term follow-up data, we should interpret negative QFT-G results with some caution.

Low Yield of Chest Radiography in a Large Tuberculosis Screening Program

“…First, we were unable to retrospectively obtain personal data (country of origin, TB exposure history) for the individuals whose chest radiographs were evaluated because of limited access to pre-employment data. However, as described, we recently evaluated LTBI risk factors and test results (TST and in vitro diagnostic laboratory test) in a group of newly hired HCWs at our institution ( 7 ). We believe that the smaller group in that study provides a valid representation of the larger group evaluated here.…”

IFN-γ release assay versus tuberculin skin test for monitoring TB infection in healthcare workers

“…For an optimal assessment of the variability of IGRA in serial testing, studies should be performed in low exposure settings in order to estimate the natural variability of the immune response to M. tuberculosis. A total of 15 studies on serial testing are available: one study from a country with high TB incidence [79], five studies from intermediate countries [14,[80][81][82][83] and nine studies from countries with low TB incidence [74,[84][85][86][87][88][89][90][91].…”

Within-Subject Variability of Mycobacterium tuberculosis-Specific Gamma Interferon Responses in German Health Care Workers

“…Studies on reproducibility and within-subject variability were predominantly from high-incidence settings (India and South Africa) and included only small numbers of subjects (67 in total) (6,32,34). In contrast, serial testing studies were mostly from countries with a low to intermediate TB incidence (5,13,20,(24)(25)(26)36). Across the board, these studies indicate that IGRA conversions and reversions occur at variable rates due to significant variability and that the manufacturers' simplistic dichotomous negative-to-positive cutoffs may not be appropriate for the interpretation of repeat IGRA results.…”