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, Oct 04, 2015
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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.
    BMC Public Health 04/2013; 13(1):353. DOI:10.1186/1471-2458-13-353 · 2.26 Impact Factor
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    ABSTRACT: Although North American hospitals are switching from tuberculin testing (TST) to interferon-gamma release assays (IGRAs), data are limited on the association between occupational exposure and serial QuantiFERON-TB Gold In-Tube (QFT) results in healthcare workers (HCWs). In a cohort of Canadian HCWs, TST and QFT were performed at study enrolment (TST1 and QFT1) and 1 year later (TST2 and QFT2). Conversion and reversion rates were estimated, and correlation with TB exposure was assessed. Among 258 HCWs, median age was 36.8 years, 188/258 (73%) were female and 183/258 (71%) were Canadian-born. In 245 subjects with a negative QFT1 we found a QFT conversion rate of 5.3% (13/245, 95% CI 2.9-8.9%). Using more stringent definitions, QFT conversion rates ranged from 2.0 to 5.3%. No TST conversions were found among the 241 HCWs with negative TST1, and no measure of recent TB exposure was associated with QFT conversions. In the 13 HCWs with a positive QFT1, 62% reverted. Using the conventional QFT conversion definition, we found a higher than expected rate of conversion. Recent occupational exposures were not associated with QFT conversions, and no TST conversions occurred in this cohort, suggesting the 'conversions' may not reflect new TB infection.
    PLoS ONE 01/2013; 8(1):e54748. DOI:10.1371/journal.pone.0054748 · 3.23 Impact Factor
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    ABSTRACT: Interferon gamma release assays (IGRAs) have been shown to be highly dynamic tests when used in serial testing for TB infection. However, there is little information demonstrating a clear association between TB exposure and IGRA responses over time, particularly in high TB incidence settings. To assess whether QuantiFERON-TB Gold In-Tube (QFT) responses are associated with occupational TB exposures in a cohort of young health care trainees in India. All medical and nursing students at Mahatma Gandhi Institute of Medical Sciences were approached. Participants were followed up for 18months; QFT was performed 4 times, once every 6months. Various modeling approaches were used to define IFN-gamma trajectories and correlations with TB exposure. Among 270 medical and nursing trainees, high rates of conversions (6.3-20.9%) and reversions (20.0-26.2%) were found depending on the definitions used. Stable converters were more likely to have had TB exposure in hospital pre-study. Recent occupational exposures were not consistently associated with QFT responses over time. IFN-gamma responses and rates of change could not be explained by occupational exposure investigated. High conversion and subsequent reversion rates suggest many health care workers (HCWs) would revert in the absence of treatment, either by clearing the infection naturally or due to fluctuations in the underlying immunological response and/or poor assay reproducibility. QFT may not be an ideal diagnostic test for repeated screening of HCWs in a high TB incidence setting.
    06/2013; 3(2):105-17. DOI:10.1016/j.jegh.2013.03.003
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