Use of a T Cell Interferon-γ Release Assay to Evaluate Tuberculosis Risk in Newly Qualified Physicians in Singapore Healthcare Institutions

Chee, C. B. E.; Lim, Louis W.; Barkham, T. M. S.; Koh, Dow Rhoon; Lam, Stanley; Shen, Lei; Wang, Y. T.

doi:10.1086/599284

Cited by 19 publications

(20 citation statements)

References 18 publications

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“…The twenty-eight students were admitted to the education, engineering, social and information studies, and health science or medicine. These data are consistent with the higher positive ratios for IGRAs reported for international students as compared with medical students in Singapore (4.3%) (Chee et al 2009). On the other hand, the low percentage of LTBI-positive Japanese medical students (< 1%) was consistent with a survey conducted in German nursing students (Schablon et al 2011).…”

Section: Discussionsupporting

confidence: 89%

Tuberculosis Screening Using a T-Cell Interferon-γ Release Assay in Japanese Medical Students and Non-Japanese International Students

Ogiwara

Kimura

Tokue

et al. 2013

Tohoku J. Exp. Med.

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Screening of medical students and international students for tuberculosis (TB) at the time of admission is a key strategy to control and prevent the spread of infection on university campus and teaching hospitals because of the high risk of exposure to TB patients. The Mycobacterium tuberculosis antigen-specific T-cell interferon-γ release assays (IGRAs) are specific latent tuberculosis detection methods used in such groups. Currently, in Japan, there are no guidelines and no baseline data on IGRAs to evaluate the risk of TB in these high-risk groups. In order to evaluate TB risk at the time of admission in university campus and medical schools in Japan, a retrospective study was conducted. A total of 969 students (585 Japanese students and 384 international students) were screened for TB using the IGRAs at the time of admission. Eight Japanese students (0.9%) were positive for IGRAs, but none were diagnosed with active TB at the follow-up. In contrast, 30 international students (7.8%) were positive for IGRAs, including two students diagnosed with active TB during follow up. Positive ratio of IGRAs in international students was significantly higher than that of medical students at the time of admission. Here we propose a standard approach for TB screening with IGRAs at the time of admission for medical students and international students in Japan.

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Section: Discussionsupporting

confidence: 89%

Tuberculosis Screening Using a T-Cell Interferon-γ Release Assay in Japanese Medical Students and Non-Japanese International Students

Ogiwara

Kimura

Tokue

et al. 2013

Tohoku J. Exp. Med.

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“…These normal limits of test variability contribute to current thresholds (>10 mm) for skin test conversion (37). Although IGRAs may be more specific than the TST and initially identify fewer persons requiring preventive therapy in some settings (38), subsequent conversions and reversions may occur with greater frequency (7,11,39,40). The reasons for this remain speculative, with possible Figure 1.…”

Section: Discussionmentioning

confidence: 99%

Test Variability of the QuantiFERON-TB Gold In-Tube Assay in Clinical Practice

Metcalfe

Cattamanchi

McCulloch

et al. 2013

Am J Respir Crit Care Med

166

107

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Rationale: Although IFN-g release assays (IGRAs) are widely used to screen for Mycobacterium tuberculosis infection in high-income countries, published data on repeatability are limited. Objectives: To determine IGRA repeatability. Methods: The study population included consecutive patients referred to The Methodist Hospital (Houston, TX) between August 1, 2010 and July 31, 2011 for latent tuberculosis (TB) infection screening with an IGRA (QuantiFERON-TB Gold In-Tube; Cellestis, Carnegie, Australia). We performed multiple IGRA tests using leftover stimulated plasma according to a prospectively formulated quality control protocol. We analyzed agreement in interpretation of test results classified according to manufacturer-recommended criteria and repeatability of quantitative TB response. Measurements and Main Results: During the study period, 1,086 test results were obtained from 543 subjects. Per the manufacturer's cutpoint, the result of the second test was discordant from that of the first in 28 (8%) of 366 patients with valid test results, including 13 with an initial negative result and 15 with an initial positive result. Although agreement between repeat test results was high (k ¼ 0.84; 95% confidence interval, 0.79-0.90), the normal expected range of within-subject variability in TB response on retesting included differences of 6 0.60 IU/ml for all individuals (coefficient of variation, 14%), and 6 0.24 IU/ml (coefficient of variation, 27%) for individuals whose initial TB response was between 0.25 and 0.80 IU/ml. Conclusions: There is substantial variability in TB response when IGRAs are repeated using the same patient sample. IGRA results should be interpreted cautiously when TB response is near interpretation cut-points.Keywords: interferon-g release assay; QuantiFERON; repeatability; imprecision IFN-g release assays (IGRAs) are in vitro immunodiagnostic tests that measure effector T cell-mediated IFN-g response to synthetic Mycobacterium tuberculosis-specific polypeptides. The QuantiFERON-TB Gold In-Tube (QFT-GIT; Cellestis, Carnegie, Australia) is a commercially available IGRA that has been recommended as an alternative to the tuberculin skin test (TST) in targeted screening for M. tuberculosis infection (1).Although IGRAs are widely used in high-income countries and numerous studies have evaluated their diagnostic performance, there are limited data on the precision of IGRA results. Clinically, such data are essential because treatment decisions could be impacted by interpretation of results close to the threshold for a positive test, and for changes above or below this threshold when serial testing is performed (2). Data on test imprecision, including repeatability (serial testing under identical conditions) and reproducibility (serial testing under changed conditions) (3) (see Table 1), are required for CE (Conformité Européene) Marking in the European Union and for premarket approval of in vitro diagnostic tests by the US Food and Drug Administration (FDA) (4).Repeatability is unaffected by inte...

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“…This is evident from recent experiences of North American hospitals that began implementing IGRAs for employee screening after the 2005 Centers for Disease Control and Prevention (CDC) guidelines, which recommended that a change from a negative to a positive IGRA result (using the diagnostic IFN-␥ cutoff of Ն0.35 IU/ml) can be treated as a "conversion" (71)(72)(73)(74). These studies have reported high rates of IGRA conversions and reversions, a phenomenon noted in other studies in settings of low TB incidence as well (75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85) (Table 2).…”

Section: Hcws and Serial Testingmentioning

confidence: 95%

Gamma Interferon Release Assays for Detection of Mycobacterium tuberculosis Infection

et al. 2014

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SUMMARY Identification and treatment of latent tuberculosis infection (LTBI) can substantially reduce the risk of developing active disease. However, there is no diagnostic gold standard for LTBI. Two tests are available for identification of LTBI: the tuberculin skin test (TST) and the gamma interferon (IFN-γ) release assay (IGRA). Evidence suggests that both TST and IGRA are acceptable but imperfect tests. They represent indirect markers of Mycobacterium tuberculosis exposure and indicate a cellular immune response to M. tuberculosis . Neither test can accurately differentiate between LTBI and active TB, distinguish reactivation from reinfection, or resolve the various stages within the spectrum of M. tuberculosis infection. Both TST and IGRA have reduced sensitivity in immunocompromised patients and have low predictive value for progression to active TB. To maximize the positive predictive value of existing tests, LTBI screening should be reserved for those who are at sufficiently high risk of progressing to disease. Such high-risk individuals may be identifiable by using multivariable risk prediction models that incorporate test results with risk factors and using serial testing to resolve underlying phenotypes. In the longer term, basic research is necessary to identify highly predictive biomarkers.

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Use of a T Cell Interferon-γ Release Assay to Evaluate Tuberculosis Risk in Newly Qualified Physicians in Singapore Healthcare Institutions

Cited by 19 publications

References 18 publications

Tuberculosis Screening Using a T-Cell Interferon-<i>γ</i> Release Assay in Japanese Medical Students and Non-Japanese International Students

Tuberculosis Screening Using a T-Cell Interferon-<i>γ</i> Release Assay in Japanese Medical Students and Non-Japanese International Students

Test Variability of the QuantiFERON-TB Gold In-Tube Assay in Clinical Practice

Gamma Interferon Release Assays for Detection of Mycobacterium tuberculosis Infection

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