Serial Testing of Health Care Workers for Tuberculosis Using Interferon-γ Assay

Abstract

Rationale: Although interferon-␥ (IFN-␥) assays are promising alternatives to the tuberculin skin test (TST), their serial testing performance is unknown. Objective: To compare TST and IFN-␥ 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-␥ less than 0.35 and follow-up IFN-␥ greater than or equal to 0.35 or 0.70 IU/ml. QFT reversions were defined as baseline IFN-␥ greater than or equal to 0.35 and followup IFN-␥ 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] ϭ 5.3-15.5) using the 6 mm increment definition, and 6 (4.1%; 95% CI ϭ 1.5-8.7) using the 10 mm increment definition. QFT conversions occurred in 17/147 participants (11.6%; 95% CI ϭ 6.9-17.9) using the definition of IFN-␥ greater than or equal to 0.35 IU/ml, and 11/147 participants (7.5%; 95% CI ϭ 3.8-13.0) using IFN-␥ greater than or equal to 0.70 IU/ml. Agreement between TST (10 mm increment) and QFT conversions (у 0.70 IU/ml) was 96% ( ϭ 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 Ͻ 0.001). Conclusions: IFN-␥ 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.

Clinical evaluation of QuantiFERON TB-2G test for immunocompromised patients

“…This also applies to the use of the T-SPOT.TB in subgroups with impaired cellular immunity, with a recent report that HIV-infected subjects tested with the T-SPOT.TB showed only one (3%) indeterminate result, and that positive control responses were not adversely affected by CD4 counts [22]. Otherwise, a new IFN-c release assay including MTB-specific antigen (TB 7.7; QuantiFERON TB-Gold In-Tube; Cellestis Ltd) [23] has recently been developed and will replace the QFT-TB-2G test in Japan as soon as possible. Immunocompromised patients suspected of TB infection had to be examined using the QFT-TB test in the present study because only this test is currently commercially available in Japan.…”

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.…”

“…Various borderline zones around the manufacturers' thresh-olds and definitions of conversions and reversions have been proposed to improve their interpretation in serial testing (15,20,21,24,32,34). Apparently, the performance of IGRAs depends on the population and epidemiologic setting in which these tests are applied (9).…”

Spectrum of latent tuberculosis — existing tests cannot resolve the underlying phenotypes

“…Repeated tuberculin tests are rarely carried out because of the belief that, once positive, a TST is likely to remain positive and, therefore, not clinically useful; even when tests are repeated, the results are hard to interpret. Serial IGRA testing shows that IGRAs are highly dynamic, with high rates of conversions and reversions [8][9][10][11][12][13][14] . Although some of the dynamic changes may be due to test reproducibility 13,15 , some of the kinetics might signal the underlying transitions that occur in the TB spectrum.…”

“…On the basis of the research that I and others have carried out [8][9][10][11][12][13][14] , I believe that serial IGRA testing can reveal interesting underlying phenotypes that have different histories and trajectories (FIG. 1).…”