Evaluation of Interferon-Gamma Release Assays in the Diagnosis of Recent Tuberculosis Infection in Health Care Workers

Abstract

BackgroundHealth care workers (HCWs) are a group at risk of latent tuberculosis infection (LTBI). The aims of this study were to determine IFN-γ response by QuantiFERON-TB GOLD In Tube (QFN-G-IT) and T-SPOT.TB in HCWs, comparing the results with tuberculin skin test (TST); and to analyze the capacity of IFN-γ tests to detect recent versus remote LTBI with a prolonged stimulation test (PST).Methodology/Principal FindingsA total of 147 HCWs were enrolled; 23 of whom were BCG vaccinated. 95 HCWs (64.6%) had a previous positive TST and were not retested; and 52 HCWs had a previous negative TST or were tested for the first time. When we analysed individuals without previous positive TST, the number of positive results for T-SPOT.TB was 12/52 (23.1%); and for QFN-G-IT, 9/52 (17.3%). The global concordance (κ) between T-SPOT.TB and QFN-G-IT with TST was 0.754 and 0.929 respectively. Of individuals with previous positive TST, T-SPOT.TB and QFN-G-IT were negative in 51.6% (49/95) and 62.1% (59/95) respectively, decreasing the concordance to 0.321 and 0.288, respectively. In non-BCG vaccinated HCWs with previous positive TST a positive IFN-γ test was associated with degree of exposure and diameter of TST. PST was performed in 24 HCW with previous positive TST and negative IFN-γ tests. PST was developed in 3 cell cultures stimulated with medium alone, ESAT-6 and CFP-10, respectively. In the third and sixth day of incubation period, part of the supernatants were replaced with complete medium supplemented with (rIL)-2. On day 9, ELISPOT assay was performed. In 14 samples PST was not valid due to not having enough cells. In 8 cases, the response was negative, and in 2 cases positive, suggesting that these patients were infected with Mycobacterium tuberculosis in some point in the past.ConclusionsBoth IFN-γ tests showed a similar number of positive results, and concordance between the tests was excellent. None of the tests was affected by prior BCG vaccination. IFN-γ tests are a useful tool for detecting recent infection in HCW population.

Diagnosis of tuberculosis infection using interferon-γ-based assays

“…Serial TST testing may induce a boosting phenomenon, compromising its interpretation. 10 In a study performed in Barcelona (Spain), 11 prevalence of LTBI in HCWs without a previous positive TST was higher according to T-SPOT.TB (23.1%), and QFT-IT (17.3%) than according to TST (15.4%). Positive IFN-γ tests were associated with age and degree of occupational exposure, but not with BCG vaccination, a finding consistent with previous studies with QFT-G tests.…”

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

“…Routine TB screening for HCW is considered as a cornerstone for preventing TB in hospitals and it is performed in many highincome countries, for example, USA [9], Japan [21], France [22], Spain [23] and Switzerland [24]. In the UK, TB screening of HCW is mainly performed as a pre-employment screening [25].…”

“…Different vaccines, different age at vaccination and different revaccination schemas might be responsible for this lack of correlation. Most of these studies were performed with QFT, but six studies used the T.SPOT.TB and showed basically the same results [23,51,52,62,64,70]. All but one showed lower proportions of positive T-SPOT.TB than positive TST and the differences were statistically significant [52].…”

“…The difference in Review the prevalence of positive TST and IGRA was not statistically significant in seven studies [25,48,[53][54][55][56][57]. In the other 24 studies, the difference was statistically significant [13,21,23,27,30,46,47,[49][50][51][58][59][60][61][62][63][64][65][66][67][68][69][70]. However, there was no clear trend that TST-positive/ IGRA-negative discordant results increased with an increasing proportion of BCG-vaccinated HCW in the study populations.…”

“…Table 1 lists studies with a head-to-head comparison of TST and IGRA results in HCW that allow the display of the concordant and discordant results. The results of 11 studies comprising a total of 3733 HCW are provided [13,22,23,25,27,50,53,55,59,62,67]. Concerning discordant results, the proportion of IGRAnegative/TST-positive discordance is ten-times larger than IGRApositive/TST-negative discordance (29.5 vs 2.7% of all HCW tested).…”