Interferon-Gamma Release Assays for Screening of Health Care Workers in Low Tuberculosis Incidence Settings: Dynamic Patterns and Interpretational Challenges

Pai, Madhukar; Elwood, Kevin

doi:10.1155/2012/420392

Cited by 22 publications

(15 citation statements)

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“…For example, IGRAs would be preferable to the TST in populations where BCG is given after infancy or given multiple times (19,21). In contrast, TST is preferable to the IGRAs for serial testing of health care workers, because IGRAs produce high rates of conversions and reversions and are harder to interpret for occupational health programs (3,41,50).…”

Section: Discussionmentioning

confidence: 99%

Latent Mycobacterium tuberculosis Infection and Interferon-Gamma Release Assays

Pai

Behr

2016

Microbiol Spectr

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The identification of individuals with latent tuberculosis infection (LTBI) is useful for both fundamental understanding of the pathogenesis of disease and for clinical and public health interventions (i.e., to prevent progression to disease). Basic research suggests there is a pathogenetic continuum from exposure to infection to disease, and individuals may advance or reverse positions within the spectrum, depending on changes in the host immunity. Unfortunately, there is no diagnostic test that resolves the various stages within the spectrum of Mycobacterium tuberculosis infection. Two main immune-based approaches are currently used for identification of LTBI: the tuberculin skin test (TST) and the interferon-gamma release assay (IGRA). TST can use either the conventional purified protein derivative or more specific antigens. Extensive research suggests that both TST and IGRA represent indirect markers of M. tuberculosis exposure and indicates a cellular immune response to M. tuberculosis . The imperfect concordance between these two tests suggests that neither test is perfect, presumably due to both technical and biological reasons. Neither test can accurately differentiate between LTBI and active TB. Both IGRA and TST have low sensitivity in a variety of immunocompromised populations. Cohort studies have shown that both TST and IGRA have low predictive value for progression from infection to active TB. For fundamental applications, basic research is necessary to identify those at highest risk of disease with a positive TST and/or IGRA. For clinical applications, the identification of such biomarkers can help prioritize efforts to interrupt progression to disease through preventive therapy.

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Section: Discussionmentioning

confidence: 99%

Latent Mycobacterium tuberculosis Infection and Interferon-Gamma Release Assays

Pai

Behr

2016

Microbiol Spectr

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“…4) There are limited longitudinal data on the prognosis of such phenotypes, and it is unclear whether any subgroup should be targeted for preventive therapy. As summarized in recent reviews (49,90), IGRAs are inherently dynamic in a serial testing context, and this is reflected in the literature, which consistently shows high rates of both conversions and reversions. There are no data to date to suggest that IGRAs are better at identifying the incidence of new TB infection than the TST, and in fact, when manufacturer's dichotomous cutoffs are used for conversions, they will likely result in conversion rates that are incompatible with what is epidemiologically expected for a given setting.…”

Section: Hcws and Serial Testingmentioning

confidence: 97%

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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“…Pai et al postulate the simple dichotomous definition of IGRA test results to be inappropriate as it causes higher conversion rates than what the annual TB infection risk in low-incidence settings would lead to expect [15]. Several studies suggest the use of a borderline zone in order to avoid unnecessary X-rays and preventive chemotherapy [9, 16–20].…”

Section: Introductionmentioning

confidence: 99%

QFT-Plus: a plus in variability? – Evaluation of new generation IGRA in serial testing of students with a migration background in Germany

Knierer

Morales

Schablon

et al. 2017

J Occup Med Toxicol

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BackgroundCurrently available Interferon-gamma release assays (IGRAs) show a considerable variability in serial testing for latent tuberculosis infection (LTBI).This study offers first results for the new generation IGRA QuantiFERON-TB Gold Plus (QFT-Plus) introduced in 2015 in comparison with its predecessor QuantiFERON-TB Gold In-Tube (QFT-GIT) from serial testing of students with a migration background at German universities.MethodsForty-one students were selected from a previous study. All students with a positive IGRA were asked and 11 agreed to participate in this cohort study. Additionally 30 students with negative IGRA results were selected by chance. Weekly testing with QFT-Plus and QFT-GIT was performed in all individuals over a 4-week period. IGRA variability was evaluated by calculating conversion and reversion rates.ResultsFrom 41 participants a total number of 163 serial measurements were analyzed for each IGRA, leading to 122 possible IGRA changes each. QFT-Plus had four conversions and two reversions leading to a conversion rate of 4.3% (4 of 93 possible conversions, 95% CI 1.4–11.3%) and reversion rate of 6.9% (2 of 29 possible reversions, 95% CI 1.2–24.2%). QFT-GIT had 2 conversions and 1 reversion causing slightly lower rates with 2.2% conversions (2 of 91, 95% CI 0.4–8.5%) and 3.2% reversions (1 of 31, 95% CI 0.2–18.5%). Inconsistent IGRA results occurred in 4 subjects for QFT-Plus (8 stable positives, 29 stable negatives) and in 2 subjects for QFT-GIT (9 stable positives, 30 stable negatives). Agreement between the two IGRAs was 95.1% (κ = 0.89). Variance attributed to the individuals was low (QFT-Plus: ICC = 0.88).ConclusionThis study confirms occurrence of conversions and reversions for the new QFT-Plus in serial testing of a high-risk cohort in a low-incidence setting with improbable new TB contact during the study. QFT-Plus conversion and reversion rates were slightly higher than for the QFT-GIT but overall they were lower for both IGRAs than in other studies that investigated IGRA variability.Electronic supplementary materialThe online version of this article (doi:10.1186/s12995-016-0148-z) contains supplementary material, which is available to authorized users.

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Interferon-Gamma Release Assays for Screening of Health Care Workers in Low Tuberculosis Incidence Settings: Dynamic Patterns and Interpretational Challenges

Cited by 22 publications

References 32 publications

Latent Mycobacterium tuberculosis Infection and Interferon-Gamma Release Assays

Latent Mycobacterium tuberculosis Infection and Interferon-Gamma Release Assays

Gamma Interferon Release Assays for Detection of Mycobacterium tuberculosis Infection

QFT-Plus: a plus in variability? – Evaluation of new generation IGRA in serial testing of students with a migration background in Germany

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