Accuracy Of Interferon-gamma Release Assays Research Articles

Diagnostic accuracy of interferon-gamma release assays for diagnosis of smear-negative pulmonary tuberculosis: a systematic review and meta-analysis

IntroductionThe diagnosis of smear-negative pulmonary tuberculosis (SNPTB) is challenging. Interferon gamma-release assays (IGRAs) may be helpful in early diagnosis among these patients resulting in prompt treatment and favorable outcomes.MethodsWe performed a comprehensive search from each databases’ inception to April 5, 2021. The studies that provided sufficient data regarding the sensitivity and specificity of IGRAs included QuantiFERON-TB Gold In-Tube (QFT-GIT), T-SPOT.TB, or QuantiFERON-TB Gold Plus for diagnosis of SNPTB were included.ResultsOf 1,312 studies screened, 16 studies were included; 11 QFT-GIT, 2 T-SPOT.TB, and 3 QFT-GIT and T-SPOT.TB. For diagnosis of SNPTB, QFT-GIT had sensitivity of 0.77 (95% CI 0.71–0.82), specificity of 0.70 (95% CI 0.58–0.80), diagnostic odds ratio (DOR) of 8.03 (95% CI 4.51–14.31), positive likelihood ratio (LR) of 2.61 (95% CI 1.80–3.80), negative LR of 0.33 (95% CI 0.25–0.42), and area under receiver operating characteristic (AUROC) of 0.81 (95% CI 0.77–0.84). T-SPOT.TB had sensitivity of 0.74 (95% CI 0.71–0.78), specificity of 0.71 (95% CI 0.49–0.86), DOR of 6.96 (95% CI 2.31–20.98), positive LR of 2.53 (95% CI 1.26–5.07), negative LR of 0.36 (95% CI 0.24–0.55), and AUROC of 0.77 (95% CI 0.73–0.80). The specificity seemed lower in the subgroup analyses of studies from high tuberculosis burden counties compared to the studies from low tuberculosis burden.ConclusionIGRAs do have insufficient diagnostic performance for SNPTB. However, the tests are still helpful to exclude tuberculosis among patients with low pre-test probability.Registry: PROSPERO: CRD42021274653.

Diagnostic performance of interferon-gamma release assay for diagnosis of tuberculous pericarditis: A meta-analysis.

The diagnosis of tuberculous pericarditis is difficult to set, not only for its non-specific clinical presentation, but also for the lack of useful diagnostic tests. We comprehensively evaluate the overall diagnostic accuracy of Interferon-gamma release assays (IGRA) upon tuberculous pericarditis by meta-analysis. We searched PubMed, Embase and Cochrane Library database from the earliest available date of indexing through April 30, 2019. The study quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS2) checklist. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios (LR+ and LR-) and constructed summary receiver operating characteristic curves parameters. Across six results from five studies (415 patients), the pooled sensitivity for IGRA methods was 0.94 (95% confidence interval [CI]; 0.87-0.98) with heterogeneity (χ2 =69.9, P=.01) and a pooled specificity of 0.94 (95% CI; 0.75-0.94) without heterogeneity (χ2 =41.1, P=.13). Likelihood ratio (LR) syntheses gave an overall positive likelihood ratio (LR+) of 16.8 (95% CI; 8.0-35.4) and negative likelihood ratio (LR-) of 0.06 (95% CI; 0.03-0.13). The pooled diagnostic odds ratio was 278 (95% CI; 114-6806). Interferon-gamma release assays demonstrated good sensitivity and specificity for diagnosis of tuberculous pericarditis. At present, the literature regarding remains the use of IGRA for diagnosis of tuberculous pericarditis still limited; thus, further large multicenter studies would be necessary to substantiate the diagnostic accuracy of IGRA test for the diagnosis of tuberculous pericarditis.

Latent tuberculosis infection in transplant candidates: a systematic review and meta-analysis on TST and IGRA.

The diagnostic accuracy of interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST) for latent tuberculosis infection (LTBI) in transplant candidates is uncertain. Pubmed, Embase and Cochrane library were searched to identify relevant studies. Quality of included studies was assessed with RevMan5 software (via GUADAS2 checklist). Accuracy measures of IGRAs and TST assays (sensitivity, specificity and others) were pooled with random effects model. Data were analyzed by STATA and Meta-DiSc. Twenty-eight studies were selected for full review, and 16 were included in the final analysis. The pooled sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) for TST were 46% [95% confidence interval (CI) 38-54%], 86% (95% CI 75-93%), 46.3% (95% CI 40-52), 88.7% (95% CI 87-89), 3.3 (95% CI 1.6-6.4), 0.63 (95% CI 0.52-0.77) and 5 (95% CI 2-12), respectively. For QFT-G, the pooled sensitivity, specificity, PPV, NPV, PLR, NLR, and DOR were 58% (95% CI 41-73%), 89% (95% CI 77-95%), 72.7% (95% CI 68-76), 80.6% (95% CI 78-82), 5.3 (95% CI 2.0-14.0), 0.47 (95% CI 0.30-0.75) and 11 (95% CI 3-46), respectively. Likewise, for T-SPOT.TB, the pooled sensitivity, specificity, PPV, NPV, PLR, NLR, and DOR were 55% (95% CI 40-70%), 92% (95% CI 87-95%), 60.4% (95% CI 47-72), 90.2% (95% CI 86-92), 6.7 (95% CI 4.0-11.1), 0.52 (95% CI 0.31-0.85) and 16 (95% CI 7-37), respectively. IGRAs were more sensitive and specific than the TST with regard to the diagnosis of LTBI in the transplant candidates. They have added value and can be complementary to TST.

Diagnostic accuracy of interferon-gamma release assays for tuberculous meningitis: a meta-analysis.

To evaluate the diagnostic accuracy of interferon-gamma release assays (IGRAs) for diagnosing tuberculous meningitis (TBM). The EMBASE and PubMed databases were systematically searched to identify studies published by 2 May 2015 investigating the diagnostic accuracy of IGRA for TBM. The quality of the included studies was assessed using the revised Quality Assessment for Studies of Diagnostic Accuracy (QUADAS-2) method. The overall diagnostic accuracies of an IGRA for cerebrospinal fluid (CSF) or blood were pooled using a bivariate model. Eight studies using blood IGRA and 6 studies using CSF IGRA were included. The overall sensitivities for blood and CSF IGRA were respectively 0.78 and 0.77, and the specificities were 0.61 and 0.88. The areas under the summary receiver operating characteristic curves were respectively 0.76 and 0.83 for blood and CSF IGRA. The major design weaknesses of the studies included were patient selection bias and exclusion of uninterpretable results. The diagnostic accuracy of blood and CSF IGRA in case of TBM is moderate.

A retrospective review of the two-step tuberculin skin test in dialysis patients.

BackgroundReactivation of latent Mycobacterium tuberculosis infection (LTBI) is a health concern for patients on dialysis or receiving a kidney transplant, as these patients are often immunosuppressed. The most frequently used test for LTBI screening in this population is the tuberculin skin test (TST). The diagnostic accuracy (sensitivity and specificity) of the TST in a contemporary North American or Western European dialysis population is unknown.ObjectivesOur objective was to determine the diagnostic accuracy and clinical utility of the two-step TST in patients receiving dialysis.DesignThis is a retrospective cohort study.SettingThis study is set at four tertiary dialysis units across Winnipeg, Manitoba.PatientsThere are 483 chronic hemodialysis and peritoneal dialysis patients in the study.MeasurementsThe measurements are sensitivity and specificity of the TST with respect to abnormal chest X-ray.MethodsAll patients received a two-step TST and assessment of risk factors for prior tuberculosis (TB) infection between February 2008 and December 2008. This cohort was retrospectively linked to our tuberculosis registry to ascertain if prophylaxis was received for LTBI.ResultsAt an induration cutoff of 5 mm, 62 (13 %) patients had a positive two-step TST. Patients with a known Bacillus Calmette-Guérin (BCG) vaccination were more likely to test positive (50 % of those with a positive TST had a BCG versus 34 % with a negative TST, p = 0.05). Using a diagnostic gold standard of an abnormal chest X-ray as a proxy for LTBI, the sensitivity of the TST was only 14 % and the specificity was 88 %. Only 8 of 62 patients with a positive TST (13 %) received prophylaxis for LTBI. None of the patients who tested negative were treated.LimitationsThere is a lack of a truly accurate gold standard for LTBI.ConclusionsThe TST has limited diagnostic and clinical utility for LTBI screening in patients on dialysis. Further research into the diagnostic accuracy of interferon-gamma release assays and a revision of LTBI screening guidelines in patients on dialysis should be considered.Electronic supplementary materialThe online version of this article (doi:10.1186/s40697-016-0119-4) contains supplementary material, which is available to authorized users.

Implementation of an Interferon-Gamma Release Assay to Screen for Tuberculosis in Refugees and Immigrants

Despite increased use and accuracy of interferon-gamma release assays to detect latent tuberculosis infection (LTBI) in foreign-born arrivals in the United States, risk characteristics associated with positive results are not well characterized. We conducted a retrospective record review of 541 refugees and immigrants screened for LTBI with QuantiFERON(®)-TB Gold In-Tube (QFT-IT) at the Spokane Public Health Clinic from January 2, 2008, through June 5, 2009. Overall, 24% of the arrivals had a positive QFT-IT, with the greatest frequency of positive results occurring in arrivals from Liberia (100%) and Bhutan (39%). More than the expected number of Burmese had indeterminate QFT-IT results. A positive QFT-IT was associated with age, race, ethnicity, and extent of TB burden in the country of origin. QFT-IT is useful to screen for LTBI in foreign-born arrivals, particularly middle-aged adults from high-burden countries. However, the QFT-IT may not yield meaningful results in groups with significant immunocompromise.

Evaluation of interferon-gamma release assays for the diagnosis of tuberculosis: an updated meta-analysis

The objective of this investigation was to systematically evaluate the diagnostic accuracy of interferon-gamma release assays (IGRAs) for tuberculosis disease. Both English and Chinese databases were searched for relevant articles through January 2012. We included studies that were restricted to diagnostic applications of IGRAs in patients with active tuberculosis and excluded studies performed in the immune-compromised population. We used Meta-DiSc software to handle the data. We calculated the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and 95% confidence interval (CI) for each study. We also calculated the pooled sensitivity, specificity, PLR, NLR, DOR, and produced forest plots and summary receiver operating characteristic (SROC) curves. A total of 61 papers (73 studies) were eligible for meta-analysis, including 36 published in English and 25 published in the Chinese language. The overall sensitivity, specificity, PLR, NLR, DOR, and 95% CI of IGRAs were 0.85 (95% CI: 0.84-0.86), 0.84 (95% CI: 0.83-0.85), 7.82 (95% CI: 6.01-10.19), 0.17 (95% CI: 0.14-0.21), and 59.27 (95% CI: 40.19-87.42), respectively. For ten studies evaluating T-SPOT.TB in China, the combined sensitivity, specificity, PLR, NLR, DOR, and 95% CI were 0.88 (95% CI: 0.86-0.91), 0.89 (95% CI: 0.86-0.92), 8.86 (95% CI: 5.42-14.46), 0.13 (95% CI: 0.10-0.17), and 88.15 (95% CI: 41.76-186.07), respectively. The SROC area under the curve (AUC) was 0.9548 (95% CI: 0.9323-0.9773). Though IGRAs showed good sensitivity and specificity for the detection of tuberculosis in this meta-analysis, the decision to use an IGRA should be based on the local prevalence of the disease and the country guidelines, as well as resources and logistical considerations.

Neue Empfehlungen für die Umgebungsuntersuchungen bei Tuberkulose*

In 2007, the German Central Committee against Tuberculosis (DZK) published recommendations for contact tracing that introduced the new interferon gamma release assays (IGRAs). Meanwhile, substantial progress has been made in documenting the utility of IGRAs. Because IGRAs are usually superior to the tuberculin skin test (TST) in detecting latent TB infection (LTBI) with respect to sensitivity and specificity in adult contact populations that are at least partially BCG vaccinated, it is now recommended that instead of two-step testing only IGRAs be used.[nl]As the literature does not yet provide sufficient data on the accuracy of IGRAs in children younger than 5 years, the TST remains the method of choice in that age group. To date, also, no clear body of data exists to substantiate better performance for IGRAs than for the TST in older children, thus in this age group using of either test is recommended. The new recommendations also underscore the importance of a diligent preselection of close contacts in order to achieve a high probability that positive test results represent recent infection and to thus increase the benefit of chemopreventive treatment for those identified as requiring it. In a third point of update, it is noted that re-testing of contacts individuals found positive for LTBI may produce a considerable number of false-negative results and should thus be avoided in case of documented exposure.

Neue Empfehlungen für die Umgebungsuntersuchungen bei Tuberkulose

In 2007, the German Central Committee against Tuberculosis (DZK) published recommendations for contact tracing that introduced the new interferon gamma release assays (IGRAs). Meanwhile, substantial progress has been made in documenting the utility of IGRAs. Because IGRAs are usually superior to the tuberculin skin test (TST) in detecting latent TB infection (LTBI) with respect to sensitivity and specificity in adult contact populations that are at least partially BCG vaccinated, it is now recommended that instead of two-step testing only IGRAs be used.[nl]As the literature does not yet provide sufficient data on the accuracy of IGRAs in children younger than 5 years, the TST remains the method of choice in that age group. To date, also, no clear body of data exists to substantiate better performance for IGRAs than for the TST in older children, thus in this age group using of either test is recommended. The new recommendations also underscore the importance of a diligent preselection of close contacts in order to achieve a high probability that positive test results represent recent infection and to thus increase the benefit of chemopreventive treatment for those identified as requiring it. In a third point of update, it is noted that re-testing of contacts individuals found positive for LTBI may produce a considerable number of false-negative results and should thus be avoided in case of documented exposure.

Evidence-Based Comparison of Commercial Interferon-γ Release Assays for Detecting Active TB: A Metaanalysis

Test accuracy of interferon-gamma release assays (IGRAs) for diagnosing TB differs when using older or precommercial tools and inconsistent diagnostic criteria. This metaanalysis critically appraises studies investigating sensitivity and specificity of the commercial T-Spot.TB and the QuantiFERON-TB Gold In-Tube Assay (QFT-IT) among definitely confirmed TB cases. We searched Medline, EMBASE, and Cochrane bibliographies of relevant articles. Sensitivities, specificities, and indeterminate rates were pooled using a fixed effect model. Sensitivity of the tuberculin skin test (TST) was evaluated in the context of IGRA studies. In addition, the rates of indeterminates of both IGRAs were assessed. The pooled sensitivity of TST was 70% (95% CI, 0.67-0.72) compared with 81% (95% CI, 0.78-0.83) for the QFT-IT and 88% (95% CI, 0.85-0.90) for the T-Spot.TB. Sensitivity increased to 84% (95%CI, 0.81-0.87) and 89% (95% CI, 0.86-0.91) for the QFT-IT and T-Spot.TB, respectively, when restricted to performance in developed countries. In contrast, specificity of the QFT-IT was 99% (95% CI, 0.98-1.00) vs 86% for the T-Spot.TB (95% CI, 0.81-0.90). The pooled rate of indeterminate results was low, 2.1% (95% CI, 0.02-0.023) for the QFT-IT and 3.8% (95% CI, 0.035-0.042) for the T-Spot.TB, increasing to 4.4% (95% CI, 0.039-0.05) and 6.1% (95% CI, 0.052-0.071), respectively, among immunosuppressed hosts. The newest commercial IGRAs are superior, in comparison with the TST, for detecting confirmed active TB disease, especially when performed in developed countries.