Serial Testing Of Healthcare Workers Research Articles

Serial testing of healthcare workers for latent tuberculosis infection and long-term follow up for development of active tuberculosis.

BackgroundHealthcare workers (HCWs) are at high risk of tuberculosis (TB) infection due to occupational exposure. It is important to diagnose TB infections in HCWs to prevent nosocomial transmission, particularly among immunocompromised patients.ObjectiveThe aim of this study was to analyze the rate of tuberculin skin test (TST) conversion and to assess the incidence of active TB after the latent TB infection screenings in high-risk HCWs.MethodsThis retrospective cohort study involved 458 HCWs in TB-related departments between 2009 and 2013. All HCWs underwent a TST and a chest radiograph annually; an interferon-γ release assay (IGRA) was performed on the TST-converted subjects. TST-converted and IGRA-positive HCWs underwent treatment for latent TB infection.ResultsThe TST conversion rate was 30.3% from 2009 to 2011 in two years, 7.4% from 2011 to 2012, and 17.4% from 2012 to 2013. Eleven subjects out of 42 TST converters (26%) were IGRA-positive; two of them developed into active pulmonary TB during the follow-up period.ConclusionsThere was significant discordance between TST conversion and IGRA results in high-risk HCWs, and active TB developed only in TST-converted and IGRA-positive HCWs. Therefore, the combined use of TST and IGRA for periodic monitoring of TB infections in high-risk HCWs may be useful.

T-SPOT.TB Interferon-γ Release Assay Performance in Healthcare Worker Screening at Nineteen U.S. Hospitals

Interferon-γ release assays have significant advantages over tuberculin skin testing in many clinical situations. However, recent studies have called into question their reliability in serial testing of healthcare workers because of reportedly high rates of positivity and high conversion/reversion rates on retesting. To define the performance characteristics of the T-SPOT.TB test, an interferon-γ release assay, during serial screening programs of healthcare workers at 19 U.S. hospitals. A total of 42,155 T-SPOT.TB test results from healthcare workers at 19 geographically diverse hospitals obtained for routine tuberculosis screening programs were analyzed to determine the rates of positivity, reversion, and conversion in serial testing data. In 19,630 evaluable serial pairs from 16,076 healthcare workers, the mean test positivity rate was 2.3% (range, 0.0-27.4%). The mean conversion rate was 0.8% (range, 0.0-2.5%), and the mean reversion rate was 17.6%. Positivity and conversion rates correlated with known tuberculosis risk factors including age and sex. The observed specificity of the T-SPOT.TB test was at least 98.6%. The high concordance and test completion rates in this study suggest that the T-SPOT.TB test is a reliable tool for healthcare worker serial screening. As expected, the observed positivity rates were lower compared with the tuberculin skin test, likely reflecting the higher specificity of this test. Furthermore, the observed rates of conversion were low and significantly correlated with the geographic incidence of tuberculosis. Our findings suggest that the T-SPOT.TB test is an accurate and reliable way to screen healthcare workers.

Serial testing using interferon- release assays in nursing students in India

To the Editor: We have previously shown that Indian healthcare workers have higher prevalence of latent tuberculosis infection (LTBI) and are at increased risk for new infection [1]–[4]. Interferon-γ release assays (IGRAs) have been introduced as an alternative to the tuberculin skin test (TST) for diagnosing LTBI in healthcare workers and other high-risk groups. They have logistical advantages over the TST and will not cross-react with the bacille Calmette Guerin vaccine. IGRAs are now being widely used for screening healthcare workers [5], yet recent reports indicate that switching from TST to IGRAs for the serial testing of healthcare workers may result in increased rates of test conversions and reversions [3], [6]–[8]. Most of these studies are from low tuberculosis (TB) incidence settings, with limited opportunity for nosocomial TB exposure; as a result, the increased conversion rates are considered false-positive test conversions, making it difficult for clinicians to interpret IGRA test conversions in these settings [9]. It remains unclear whether IGRA conversions are associated with TB exposure in high TB incidence settings where unprotected exposure to infectious TB patients is more common among healthcare workers. To evaluate whether IGRA conversions may represent new cases of LTBI, in a high TB incidence setting, in the absence of a gold standard for LTBI, we employed TB exposure as a proxy measure. We established a cohort of nursing students who underwent IGRA testing annually for 3 years at a tertiary level hospital in southern India [1]. Annual rates of conversions and reversions were estimated in this cohort. A relationship between occupational TB exposure and change in continuous interferon-γ (IFN-γ) levels were …

Tuberculosis in healthcare workers – a narrative review from a German perspective

IntroductionDespite the decline of tuberculosis in the population at large, healthcare workers (HCW) are still at risk of infection.MethodsIn a narrative review the TB risk in HCW and preventive measures are described, with the focus on epidemiology and Occupational Safety and Health (OSH) regulations in Germany.ResultsThere is an increased risk of infection not only in pneumology and laboratories with regular contact with tuberculosis patients or infectious materials. Epidemiological studies have also verified an increased risk of infection from activities that involve close contact with patients’ breath (e.g. bronchoscopy, intubation) or close contact with patients in need of care in geriatric medicine or geriatric nursing. In occupational disease claim proceedings on account of tuberculosis, the burden of proof can be eased for insured persons who work in these or other comparable fields. Forgoing evidence of an index person as a source of infection has led to a doubling of the rate of cases of tuberculosis recognised as an occupational disease and has halved the duration of occupational disease claim proceedings in Germany. For several years now, it has been possible to use the new interferon-y release assays (IGRAs) to diagnose a latent tuberculosis infection (LTBI) with significantly greater validity than with the traditional tuberculin skin test (TST). However, variability of the IGRAs around the cut-off poses problems especially in serial testing of HCWs. At around 10%, LTBI prevalence in German healthcare workers is lower than had been assumed. It can make sense to treat a recent LTBI in a young healthcare worker so as to prevent progression into active tuberculosis. If the LTBI is occupational in origin, the provider of statutory accident insurance can cover the costs of preventive treatment. However, little is known about disease progression in HCWs with positive IGRA sofar.ConclusionTB screening in HCWs will remain an important issue in the near future even in low incidence, high income countries, as active TB in HCWs is often due to workplace exposure. The IGRAs facilitate these screenings. However, variability of IGRA results in serial testing of HCWs need further investigations.

Interferon-γ Release Assays and Tuberculin Skin Testing for Diagnosis of Latent Tuberculosis Infection in Healthcare Workers in the United States

IFN-γ release assays (IGRAs) are alternatives to tuberculin skin testing (TST) for diagnosis of latent tuberculosis infection. Limited data suggest IGRAs may not perform well for serial testing of healthcare workers (HCWs). Determine the performance characteristics of IGRAs versus TST for serial testing of HCWs. A longitudinal study involving 2,563 HCWs undergoing occupational tuberculosis screening at four healthcare institutions in the United States, where the average tuberculosis case rate ranged from 4 to 9 per 100,000 persons. QuantiFERON-TB Gold In-Tube (QFT-GIT), T-SPOT.TB (T-SPOT), and TST were performed at baseline and every 6 months for 18 months between February 2008 and March 2011. A total of 2,418 HCWs completed baseline testing, which was positive for 125 (5.2%) by TST, 118 (4.9%) by QFT-GIT, and 144 (6.0%) by T-SPOT. A baseline positive TST with negative IGRAs was associated with bacillus Calmette-Guérin (BCG) vaccination (odds ratio: 25.1 [95% confidence interval: 15.5, 40.5] vs. no BCG). Proportions of participants with test conversion during the study period were 138 of 2,263 (6.1%) for QFT-GIT, 177 of 2,137 (8.3%) for T-SPOT, and 21 of 2,293 (0.9%) for TST (P < 0.001 for QFT-GIT vs. TST and for T-SPOT vs. TST; P = 0.005 for QFT-GIT vs. T-SPOT). Of the QFT-GIT and T-SPOT converters, 81 of 106 (76.4%) and 91 of 118 (77.1%), respectively, were negative when retested 6 months later. There was negative/positive discordance for 15 of 170 (8.8%) participants by QFT-GIT and for 19 of 151 (12.6%) by T-SPOT when blood was drawn 2 weeks later. Most conversions among HCWs in low TB incidence settings appear to be false positives, and these occurred six to nine times more frequently with IGRAs than TST; repeat testing of apparent converters is warranted.

Prevalence and Incidence of Latent Tuberculosis Infection in Georgian Healthcare Workers

BackgroundTuberculosis is a major occupational hazard in low and middle-income countries. Limited data exist on serial testing of healthcare workers (HCWs) with interferon-γ release assays (IGRAs) for latent tuberculosis infection (LTBI), especially in low and middle-income countries. We sought to evaluate the rates of and risk factors for LTBI prevalence and LTBI test conversion among HCWs using the tuberculin skin test (TST) and QuantiFERON-TB Gold In-tube assay (QFT-GIT).MethodsA prospective longitudinal study was conducted among HCWs in the country of Georgia. Subjects completed a questionnaire, and TST and QFT-GIT tests were performed. LTBI testing was repeated 6-26 months after baseline testing.ResultsAmong 319 HCWs enrolled, 89% reported prior BCG vaccination, and 60% worked in TB healthcare facilities (HCFs). HCWs from TB HCFs had higher prevalence of positive QFT-GIT and TST than those from non-TB HCFs: 107/194 (55%) vs. 30/125 (31%) QFT-GIT positive (p<0.0001) and 128/189 (69%) vs. 64/119 (54%) TST positive (p = 0.01). There was fair agreement between TST and QFT-GIT (kappa = 0.42, 95% CI 0.31–0.52). In multivariate analysis, frequent contact with TB patients was associated with increased risk of positive QFT-GIT (aOR 3.04, 95% CI 1.79–5.14) but not positive TST. Increasing age was associated with increased risk of positive QFT-GIT (aOR 1.05, 95% CI 1.01–1.09) and TST (aOR 1.05, 95% CI 1.01–1.10). High rates of HCW conversion were seen: the QFT-GIT conversion rate was 22.8/100 person-years, and TST conversion rate was 17.1/100 person-years. In multivariate analysis, female HCWs had decreased risk of TST conversion (aOR 0.05, 95% CI 0.01–0.43), and older HCWs had increased risk of QFT-GIT conversion (aOR 1.07 per year, 95% CI 1.01–1.13).ConclusionLTBI prevalence and LTBI test conversion rates were high among Georgian HCWs, especially among those working at TB HCFs. These data highlight the need for increased implementation of TB infection control measures.

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

Healthcare workers (HCW) are a risk group for TB. Even in countries with low TB incidence, the risk of TB in HCW is elevated for a wide range of tasks in healthcare, and the prevention of nosocomial infection of HCW remains as a challenge. IFN-γ release assays (IGRA) facilitate the screening of HCW for latent TB infection. In comparison with the tuberculin skin test, the IGRA reduces the number of x-rays and the amount of chemoprevention needed. However, a borderline zone should be introduced for the interpretation of IGRA results in the serial testing of HCW. More data on disease progression depending on conversion and reversion in IGRA is needed and a better test, which is able to distinguish recent from remote latent TB infection, would be desirable in the future.

Challenges of Interferon-γ Release Assay Conversions in Serial Testing of Health-care Workers in a TB Control Program

Clinical data with use of serial interferon-γ release assay (IGRA) testing in US health-care workers (HCWs) are limited. A single-center, retrospective chart review was done from 2007 to 2010 of HCWs who underwent preemployment QuantiFERON-TB Gold In-Tube testing. Demographic data, bacille Calmette-Guérin history, prior tuberculin skin test result if done, and baseline and serial IGRA values were obtained. The number of IGRA converters and reverters and their subsequent management by infectious disease physicians were reviewed. Quantitative IGRA-negative values were not available. A total of 7,374 IGRAs were performed on newly hired HCWs. Of these tests, 486 (6.6%) were positive at baseline, 305 (4.1%) were indeterminate, and 6,583 (89.3%) were negative. From 2007 to 2010, 52 of 1,857 HCWs (2.8%) with serial IGRA tests were identified as converters, with a serial IGRA median value of 0.63 IU/mL. Seventy-one percent of HCWs with IGRA conversion had values ≤ 1 IU/mL. None of the converters had active TB or were part of an outbreak investigation. Clinical significance of most QuantiFERON-TB Gold In-Tube conversions in serial testing remains a challenging task for clinicians. The use of a single cutoff point criterion for IGRA may lead to overdiagnosis of new TB infections. Clinical assessment and evaluation may help to prevent unnecessary therapy in these cases. The criteria for defining conversions and reversions by establishing new cutoffs needs to be evaluated further, especially in HCWs.

Interferon-gamma release assays for the tuberculosis serial testing of health care workers: a systematic review

BackgroundInterferon-gamma release assays (IGRAs) are increasingly used in the tuberculosis (TB) screening of health care workers (HCWs). However, comparatively high rates of conversions and reversion as well as growing evidence of substantial within-subject variability of interferon-gamma responses complicate their interpretation in the serial testing of HCWs.MethodsWe conducted a systematic review on the repeat use of the two commercial IGRAs, the QuantiFERON-TB Gold or In-Tube version (QFT) and the T-SPOT.TB (T-SPOT), in the serial testing and its with-subject variability among HCWs in order to provide guidance on how to interpret serial testing results in the context of the periodic screening of subjects with an increased occupational risk of latent TB infection (LTBI) in countries with low and intermediate TB incidence rates. The Medline, Embase, and Cochrane databases were searched without restrictions. Retrieved articles were complemented by additional hand searched records. Only studies that used commercial IGRAs among HCWs apart from contact and outbreak investigations and those fulfilling further predefined criteria were included.ResultsOverall, 20 studies, five using the T-SPOT and 19 using the QFT assay, were included. Fifteen studies met eligibility criteria for serial testing and five studies for within-subject variability. Irrespective of TB incidence rates in the study’s country of origin, reversion rates were consistently higher than conversion rates (range 22–71% vs. 1–14%). Subjects with baseline results around the diagnostic threshold were more likely to show inconsistent results on retesting. The within-subject variability of interferon-gamma responses was considerable across all studies systematically assessing it.ConclusionsOn the basis of reviewed studies we advocate using a borderline zone from 0.2–0.7 IU/ml for the interpretation of repeat QFT results in the routine screening of HCWs with an increased LTBI risk. Subjects with QFT results within this borderline zone, with suspected fresh infection, and those who are considered for preventive chemotherapy should be retested with the QFT within a period of about four weeks before preventive chemotherapy is recommended. However, the available data regarding the use of the T-SPOT in the serial testing of HCWs is remarkably limited and warrants further research.

Specificity of a whole blood IGRA in German nursing students

BackgroundInterferon-gamma release assays (IGRA) are used for tuberculosis (TB) screening in healthcare workers (HCWs). However, data on specificity of IGRA in serial testing of HCWs is sparse. Therefore the specificity and the negative predictive value of the IGRA - QuantiFERON-TB Gold In-Tube (QFT) - in German nursing students was investigated.Methods194 nursing students at the start of their professional career were tested with the QFT. 14 nursing students were excluded from the specificity analysis, due to exposure to mycobacterium tuberculosis. Two of these subjects were QFT- positive. None of them developed disease during the year of follow-up. A study group of 180 students, all with very low risk of prior TB infection, remained in the specificity analysis. Subjects were monitored for at least two years with respect to the development of active TB disease. IGRA was performed at the start of the training and after one year.ResultsThe mean age of the study group (n = 180) was 23 years (range 18-53) with 70.9% female and 99.4% German born. The specificity of QFT was 98.9% (178/180; 95% CI 0.96-0.99); lowering the cut-off from 0.35 IU/ml to 0.1 IU/ml would have decreased specificity only slightly to 97.8% (176/180; 95% CI 0.94-0.99). Of the 154 nursing students available for re-testing, one student who initially scored positive reverted to negative, and one student initially negative converted to positive. None of the monitored group with initially negative QFT results developed TB disease, indicating a high negative predictive value of the IGRA in this population.ConclusionsFollowing our data, QFT can serve as an effective tool in pre-employment TB screenings for HCWs. As its negative results were stable over time, specificity of the QFT in serial testing of HCWs is high. As the risk of acquiring TB infection in the German healthcare system appears to be low, our data supports the recommendation of performing TB screening only in those HCWs with known contact to TB patients or infectious materials.

Serial testing with an interferon-γ release assay in German healthcare workers.

Aim: Data concerning conversion and reversion rates in the serial testing of healthcare workers (HCWs) is rare. So far, there is no consensus on how to define and interpret interferon-gamma release assays (IGRA) conversions and reversions, or how to deal with such results. We analysed conversion and reversion rates in the serial testing of HCWs using an IGRA.Methods: The study population comprises 287 HCWs, who participated in routine occupational safety and health screening for latent tuberculosis infection (LTBI) with the QuantiFERON-TB® Gold In-Tube assay (QFT). Four different definitions for conversion and reversion were applied: 1) transgression or regression above/below the cut-off; 2) increase from <0.2 to >0.7 IU/ml or decrease from >0.7 to <0.2 IU/ml; 3) transgression or regression above/below the cut-off plus change of ≥0.50 IU/ml; and 4) transgression or regression above/below the cut-off plus change of ≥0.70 IU/ml.Results: The highest conversion and reversion rates of 6.1% (95% CI 3.5 to 9.9) and 32.6% (95% CI 19.1 to 48.5) respectively were observed with the least stringent definition of negative to positive. The most stringent definition of an increase of ≥0.7 IU/ml above the cut-point produced the lowest conversion rate of 2.5% (95% CI 0.9 to 5.3). Using an uncertainty zone from 0.2 to 0.7 IU/ml gave low conversion (2.6%) and reversion rates (15.4%). Conclusion: Our data confirmed the findings of previous studies that suggest that a simplistic dichotomous negative to positive definition of the IGRA might be deceptive because of the high number of spontaneous conversions and reversions. Therefore using an uncertainty zone around the cut-point (e.g. 0.2 to 0.7 IU/ml) could improve the discrimination between unspecific variation around the diagnostic cut-off and true conversion or reversion.

Serial testing with the interferon-γ release assay in Portuguese healthcare workers

ObjectivesEvidence for the utility of the new Mycobacterium tuberculosis (MTB) specific IFN-γ release assays in diagnosing latent tuberculosis infection (LTBI) is growing. However, data concerning conversion and reversion rates in serial testing of healthcare workers (HCWs) with an interferon-γ release assay are sparse.MethodsBetween February 2007 and September 2009, 670 HCWs in the University Hospital of Porto, Portugal were tested at least twice with QuantiFERON-TB® Gold In-Tube (QFT) for LTBI. The tuberculin skin test (TST) was performed simultaneously. QFT was considered positive if INF-γ ≥0.35 IU/mL. TST conversion was defined as an increase ≥10 or ≥6 mm compared to a baseline TST <10 mm.ResultsThe second QFT was positive in 4.8% of the 376 HCWs with an INF-γ concentration at baseline below 0.1 IU/mL but in 48.8% of the 41 HCWs with an INF-γ concentration of 0.2 to <0.35 IU/mL. Out of 74 HCWs with a baseline INF-γ concentration ≥3.0 IU/mL, 4 (5.4%) reversed while 27 out of 55 HCWs (49%) with a baseline INF-γ concentration ≥0.35 to <0.7 IU/mL reversed to a negative QFT. Those 61 HCWs with TST conversion (increase ≥10 mm) were most often (78.7%) negative in both consecutive QFTs.ConclusionOur data suggests the use of an uncertainty zone between 0.2 and 0.7 IU/mL in serial testing with QFT. As long as the knowledge regarding disease progression in QFT-positive persons is limited, persons pertaining to this zone should be retested before being offered preventive chemotherapy.