TB Screening in Canadian Health Care Workers Using Interferon-Gamma Release Assays

Department of Epidemiology, Biostatistics & Occupational Health, McGill University, Montreal, Canada.
PLoS ONE (Impact Factor: 3.23). 08/2012; 7(8):e43014. DOI: 10.1371/journal.pone.0043014
Source: PubMed


While many North American healthcare institutions are switching from Tuberculin Skin Test (TST) to Interferon-gamma release assays (IGRAs), there is relatively limited data on association between occupational tuberculosis (TB) risk factors and test positivity and/or patterns of test discordance.
We recruited a cohort of Canadian health care workers (HCWs) in Montreal, and performed both TST and QuantiFERON-TB Gold In Tube (QFT) tests, and assessed risk factors and occupational exposure.
In a cross-sectional analysis of baseline results, the prevalence of TST positivity using the 10 mm cut-off was 5.7% (22/388, 95%CI: 3.6-8.5%), while QFT positivity was 6.2% (24/388, 95%CI: 4-9.1%). Overall agreement between the tests was poor (kappa=0.26), and 8.3% of HCWs had discordant test results, most frequently TST-/QFT+ (17/388, 4.4%). TST positivity was associated with total years worked in health care, non-occupational exposure to TB and BCG vaccination received after infancy or on multiple occasions. QFT positivity was associated with having worked as a HCW in a foreign country.
Our results suggest that LTBI prevalence as measured by either the TST or the QFT is low in this HCW population. Of concern is the high frequency of unexplainable test discordance, namely: TST-/QFT+ subjects, and the lack of any association between QFT positivity and clear-cut recent TB exposure. If these discordant results are indeed false positives, the use of QFT in lieu of TST in low TB incidence settings could result in overtreatment of uninfected individuals.

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Available from: Andrea Benedetti
    • "For example, the Canadian guidelines among others have not endorsed IGRAs for serial testing in a healthcare setting [15] [16]. Additionally , several studies have reported high rates of within-subject variability, high rates of discordant test results and high rates of conversions and reversions among HCWs screened with these novel assays [2] [15] [17]. Nevertheless, the use of IGRAs in routine screening of HCWs has been increasing [17]. "
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    ABSTRACT: Objective To assess the agreement between the tuberculin skin test (TST) and the QuantiFERON-TB Gold test (QFT-G) as pre-employment screening tests for latent tuberculosis infection (LTBI) among healthcare workers. Methods A retrospective cross-sectional study was conducted among 1412 healthcare workers who were screened for LTBI during the period from August 2009 to May 2011 at a tertiary-care hospital in the Kingdom of Saudi Arabia (KSA). The studied population was screened for LTBI using both TST and QFT-G simultaneously. The agreement between both tests was quantified using the Kappa coefficient (κ). Results Comparing the results of QFT-G with TST, the tests had a significant overall agreement of 73.7% (1040/1412; κ = 0.33; p < 0.01). Negative concordance comprised 60.1% of the results, and positive concordance comprised 13.5%. However, positive TST but negative QFT comprised 16.3% of the results, and negative TST but positive QFT-G comprised 10.1%. Concordance was significantly associated with young age, female gender, Saudi-born nationals, and early career but not job type (clinical versus non-clinical) nor status of Bacillus Calmette–Guerin (BCG) vaccination. Conclusions This study demonstrated 73.7% overall agreement between TST and QFT-G results among healthcare workers during pre-employment screening for LTBI. The results need to be confirmed in future studies before recommending QFT-G as a pre-employment screening test for LTBI.
    No preview · Article · Nov 2014 · Journal of Infection and Public Health
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    • "Several systematic reviews have suggested that IGRAs are as sensitive, and as more specific than the TST in identifying LTBI, particularly in low TB incidence settings (Zwerling et al., 2012a). However, in high-incidence settings , there were no consistent differences in the prevalence of positive tests (Zwerling et al., 2012b). "

    Preview · Article · Mar 2014 · African journal of microbiology research
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    • "This is especially relevant in countries like Norway with high coverage of BCG vaccination and discordant TST positive/IGRA negative results. In a Canadian study LTBI prevalence among HCW measured by the TST was low and the most common discordant test results were TST negative/QFT positive [35]. In contrast, we observed that a total of 33% of the HCW had TST > 10 mm, 13.7% had TST ≥ 15 mm with a frequency of only 4% QFT positivity and even HCW with the highest TST values > 25 mm were QFT negative. "
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    ABSTRACT: Background Tuberculosis (TB) presents globally a significant health problem and health care workers (HCW) are at increased risk of contracting TB infection. There is no diagnostic gold standard for latent TB infection (LTBI), but both blood based interferon-gamma release assays (IGRA) and the tuberculin skin test (TST) are used. According to the national guidelines, HCW who have been exposed for TB should be screened and offered preventive anti-TB chemotherapy, but the role of IGRA in HCW screening is still unclear. Methods A total of 387 HCW working in clinical and laboratory departments in three major hospitals in the Western region of Norway with possible exposure to TB were included in a cross-sectional study. The HCW were asked for risk factors for TB and tested with TST and the QuantiFERON®TB Gold In-Tube test (QFT). A logistic regression model analyzed the associations between risk factors for TB and positive QFT or TST. Results A total of 13 (3.4%) demonstrated a persistent positive QFT, whereas 214 (55.3%) had a positive TST (≥ 6 mm) and 53 (13.7%) a TST ≥ 15 mm. Only ten (4.7%) of the HCW with a positive TST were QFT positive. Origin from a TB-endemic country was the only risk factor associated with a positive QFT (OR 14.13, 95% CI 1.37 - 145.38, p = 0.026), whereas there was no significant association between risk factors for TB and TST ≥ 15 mm. The five HCW with an initial positive QFT that retested negative all had low interferon-gamma (IFN-γ) responses below 0.70 IU/ml when first tested. Conclusions We demonstrate a low prevalence of LTBI in HCW working in hospitals with TB patients in our region. The “IGRA-only” seems like a desirable screening strategy despite its limitations in serial testing, due to the high numbers of discordant TST positive/IGRA negative results in HCW, probably caused by BCG vaccination or boosting due to repetitive TST testing. Thus, guidelines for TB screening in HCW should be updated in order to secure accurate diagnosis of LTBI and offer proper treatment and follow-up.
    Full-text · Article · Apr 2013 · BMC Public Health
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