Interferon-gamma Release Assays For Diagnosis Research Articles

THE ROLE OF INTERFERON-GAMMA RELEASE ASSAYS IN DIAGNOSIS OF LATENT TUBERCULOSIS INFECTION IN CHILDREN.

Despite numerous published papers, diagnosis of latent tuberculosis infection (LTBI) in children is still an undefined area. The importance of this topic lies in the fact that one third of the world's population is infected with Mycobacterium (M.) tuberculosis. The majority of infected individuals are LTBI cases which make a reservoir for future active tuberculosis (TB) patients. The gold standard for LTBI detection is still undetermined and this is due to the effect of various confounding factors on existing diagnostic tests. Until a decade or so ago, throughout the last century, tuberculin skin test (TST) was the only diagnostic test for LTBI. Due to scientific advances, new in vitro assays, interferon-gamma release assays (IGRAs) were discovered recently. The sensitivities of IGRAs are a bit better than those of TST, while great progress has been made in increasing the specificity of IGRA relative to TST. Nevertheless, in the diagnosis of LTBI in children, TST still has some advantages. However, generations of IGRAs have brought many diagnostic advantages that are emphasized in this review. In a difficult procedure of diagnosing LTBI in children, performance of IGRA could be the key factor in making decision whether to use preventive therapy or not.

501. Interferon-gamma Release Assays for Diagnosis of Latent TB Infection in Chronic Kidney Disease and Dialysis Patients

Abstract Background Patients with chronic kidney disease (CKD), especially end-stage kidney disease (ESKD), are at risk of developing tuberculosis (TB). Due to their relatively immunosuppresses condition, reactivation from latent TB infection (LTBI) is the core pathogenesis in these populations. However, the prevalence of LTBI among Thai CKD patients, assessed by a high sensitivity and specificity test such as interferon-gamma release assay (IGRA), has never been thoroughly explored. We aimed to investigate the prevalence and predictors for LTBI among Thai CKD patients, including ESKD individuals receiving renal replacement therapy (RRT) either by hemodialysis (HD) or peritoneal dialysis (PD). Methods All CKD patients who underwent an investigation for LTBI status at Ramathibodi hospital were prospectively recruited from September 2020 to November 2021 and retrospectively reviewed from December 2020 to November 2021. Those with positive or borderline IGRA results using T SPOT®.TB without clinical or radiological findings compatible with active TB was diagnosed with LTBI. The LTBI prevalence was determined by CKD staging and type of dialysis. Predictors for LTBI were assessed by logistic regression analysis. Results A total of 199 CKD patients were enrolled; 102 prospectively and 97 retrospectively. There were 173 evaluable patients included with a mean (SD) age of 53 (16) years, and 44% were male. Of those, 95 (55%) had ESKD and maintained on RRT. Overall, 39 (22.5%) CKD patients had LTBI with the prevalence of 25%, 12.5%, 25%, 25% and 24.2% in those with CKD stage 1, 2, 3a, 3b and ESKD, respectively (p=0.89). Among ESKD patients, those who were maintained on HD had a higher proportion of LTBI than those on PD (28.9% vs. 5.3%, p=0.03). In multivariate analysis, drinking alcohol was significantly associated with LTBI (OR 8.51; [95%CI 1.24-58.38]; p=0.029), and HD therapy was marginally associated with LTBI (OR 8.14; [95%CI 0.95-69.91]; p=0.056) among ESKD patients. Conclusion In TB endemic settings, one-fifth of patients with CKD and a quarter of ESKD patients could carry LTBI status. Alcohol consumption and HD therapy could better identify high-risk ESKD patients and potentially screen for LBTI. Disclosures All Authors: No reported disclosures.

Interferon-gamma release assays for diagnosis of latent TB infection in chronic kidney diseases and dialysis patients.

Patients with chronic kidney disease (CKD), especially end-stage kidney disease (ESKD), are at risk of developing tuberculosis (TB). The prevalence and predictors of LTBI assessed by a high-sensitivity, high-specificity test such as an interferon-gamma release assay (IGRA) has not been thoroughly explored. All patients with CKD were prospectively recruited from September 2020 to November 2021 and retrospectively reviewed from December 2020 to November 2021. The prevalence of LTBI was determined using IGRA by CKD stage and dialysis type. Predictors of LTBI were assessed by logistic regression analysis. In total, 199 patients with CKD were enrolled (102 prospectively, 97 retrospectively). Of these, 173 patients were evaluable (mean age, 53 ± 16 years; 44% male). Ninety-five (55%) patients had ESKD and were maintained on renal replacement therapy. Overall, 39 (22.5%) patients had LTBI with a prevalence of 25.0%, 12.5%, 25.0%, 25.0%, and 24.2% among patients with CKD stage 1, 2, 3a, 3b, and ESKD, respectively (p=0.89). Among patients with ESKD, the prevalence of LTBI was higher in those on hemodialysis than in those on peritoneal dialysis (28.9% vs. 5.3%, p=0.03). In the multivariable analysis of patients with ESKD, drinking alcohol was significantly associated with LTBI (odds ratio, 8.51; 95% confidence interval, 1.24-58.38; p=0.029), and hemodialysis was marginally associated with LTBI (odds ratio, 8.14; 95% confidence interval, 0.95-69.91; p=0.056). In TB-endemic settings, 20% of patients with CKD and 25% of patients with ESKD may have LTBI. Alcohol consumption and hemodialysis can help to identify high-risk patients with ESKD and potentially screen for LBTI.

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.

AAP Publications Reaffirmed or Retired

Policy Statement: Drinking water from private wells and risks to children. Pediatrics. 2009;123(6):1599–1605. Available at: http://pediatrics.aappublications.org/content/123/6/1599.full. Reaffirmed September 2019Technical Report: Drinking water from private wells and risks to children. Pediatrics. 2009;123(6):e1123–e1137. Available at: http://pediatrics.aappublications.org/content/123/6/e1123.full. Reaffirmed September 2019Clinical Report: Generic prescribing, generic substitution, and therapeutic substitution. Pediatrics. 1987;79(5):835. Available at: http://pediatrics.aappublications.org/content/79/5/835.full.pdf+html?sid=99b78e26-e4b0-43a7-9c93-c0d3a1b81966. Reaffirmed September 2019Clinical Report: Interferon-gamma release assays for diagnosis for tuberculosis infection. Pediatrics. 2014;134(6):e1763–e1773. Available at: https://pediatrics.aappublications.org/content/134/6/e1763. Reaffirmed July 2018Policy Statement: HIV and other blood-borne viral pathogens in the athletic setting. Pediatrics. 1999;104(6):1400–1403. Available at: https://pediatrics.aappublications.org/content/104/6/1400. Retired September 2019Policy Statement: Protective eyewear for young athletes. Pediatrics. 2004;113(3):619–622. Available at: https://pediatrics.aappublications.org/content/113/3/619. Retired September 2019Policy Statement: Immunization for Streptococcus pneumoniae infections in high-risk children. Pediatrics. 2014;134(6):1230–1233. Available at: https://pediatrics.aappublications.org/content/134/6/1230. Retired July 2018

Validation and Clinical Application of Interferon-Gamma Release Assay for Diagnosis of Latent Tuberculosis Infection in Children.

Background:India has the highest tuberculosis (TB) burden, accounting for one-fifth of the global incidence and two-third of the cases in Southeast Asia with an estimated 1.9 million new cases every year. Identifying and treating latent TB infection (LTBI) can reduce the risk of development of active disease by up to 90%, thereby decreasing a major burden to the prevalence of the disease, and thus reducing potential sources in future.Aim:Early diagnosis of LTBI by tuberculin skin test (TST) and a newer interferon-gamma release assay (IGRA).Materials and Methods:Seventy-seven clinically asymptomatic household contacts (≤18 years) of confirmed pulmonary TB patients were enrolled to compare the performance of TST and IGRA to diagnose LTBI. At baseline, all participants underwent testing for IGRA and TST.Results:TST showed positivity of 22%, while IGRA demonstrated positivity of 40% in the diagnosis of latent TB. Kappa value at 95% confidence interval was 0.4753, indicates a moderate agreement between the two tests. This indicates that IGRA is a better predictor of latent TB. Maximum positive percentage was in the age group of 16–18 years in both the tests followed by 1–5 years.Aim:Early diagnosis of LTBI by tuberculin skin test (TST) and a newer interferon-gamma release assay (IGRA).

Interferon-gamma release assay for the diagnosis of latent tuberculosis infection: A latent-class analysis.

BackgroundAccurate diagnosis and subsequent treatment of latent tuberculosis infection (LTBI) is essential for TB elimination. However, the absence of a gold standard test for diagnosing LTBI makes assessment of the true prevalence of LTBI and the accuracy of diagnostic tests challenging. Bayesian latent class models can be used to make inferences about disease prevalence and the sensitivity and specificity of diagnostic tests using data on the concordance between tests. We performed the largest meta-analysis to date aiming to evaluate the performance of tuberculin skin test (TST) and interferon-gamma release assays (IGRAs) for LTBI diagnosis in various patient populations using Bayesian latent class modelling.MethodsSystematic search of PubMeb, Embase and African Index Medicus was conducted without date and language restrictions on September 11, 2017 to identify studies that compared the performance of TST and IGRAs for LTBI diagnosis. Two IGRA methods were considered: QuantiFERON-TB Gold In Tube (QFT-GIT) and T-SPOT.TB. Studies were included if they reported 2x2 agreement data between TST and QFT-GIT or T-SPOT.TB. A Bayesian latent class model was developed to estimate the sensitivity and specificity of TST and IGRAs in various populations, including immune-competent adults, immune-compromised adults and children. A TST cut-off value of 10 mm was used for immune-competent subjects and 5 mm for immune-compromised individuals.FindingsA total of 157 studies were included in the analysis. In immune-competent adults, the sensitivity of TST and QFT-GIT were estimated to be 84% (95% credible interval [CrI] 82–85%) and 52% (50–53%), respectively. The specificity of QFT-GIT was 97% (96–97%) in non-BCG-vaccinated and 93% (92–94%) in BCG-vaccinated immune-competent adults. The estimated figures for TST were 100% (99–100%) and 79% (76–82%), respectively. T-SPOT.TB has comparable specificity (97% for both tests) and better sensitivity (68% versus 52%) than QFT-GIT in immune-competent adults. In immune-compromised adults, both TST and QFT-GIT display low sensitivity but high specificity. QFT-GIT and TST are equally specific (98% for both tests) in non-BCG-vaccinated children; however, QFT-GIT is more specific than TST (98% versus 82%) in BCG-vaccinated group. TST is more sensitive than QFT-GIT (82% versus 73%) in children.ConclusionsThis study is the first to assess the utility of TST and IGRAs for LTBI diagnosis in different population groups using all available data with Bayesian latent class modelling. Our results challenge the current beliefs about the performance of LTBI screening tests, and have important implications for LTBI screening policy and practice. We estimated that the performance of IGRAs is not as reliable as previously measured in the general population. However, IGRAs are not or minimally affected by BCG and should be the preferred tests in this setting. Adoption of IGRAs in settings where BCG is widely administered will allow for a more accurate identification and treatment of LTBI.

Serial testing of interferon-gamma release assay for diagnosis of tuberculosis in HIV-infected adults

Serial testing of interferon-gamma release assay for diagnosis of tuberculosis in HIV-infected adults

Systematic review and meta-analysis on the utility of Interferon-gamma release assays for the diagnosis of Mycobacterium tuberculosis finfection in children: a 2013 update

BackgroundPrevious meta-analyses regarding the performance of interferon-gamma release assays (IGRAs) for tuberculosis diagnosis in children yielded contrasting results, probably due to different inclusion/exclusion criteria.MethodsWe systematically searched PubMed, EMBASE and Cochrane databases and calculated pooled estimates of sensitivities and specificities of QuantiFERON-TB Gold In Tube (QFT-G-IT), T-SPOT.TB, and tuberculin skin test (TST). Several sub-analysis were performed: stratification by background (low income vs. high income countries); including only microbiological confirmed TB cases; including only studies performing a simultaneous three-way comparison of the three tests, and including immunocompromised children.ResultsOverall, 31 studies (6183 children) for QFT-G-IT, 14 studies (2518 children) for T-SPOT.TB and 34 studies (6439 children) for TST were included in the analyses. In high income countries QFT-G-IT sensitivity was 0.79 (95%IC: 0.75-0.82) considering all the studies, 0.78 (95%CI:0.70-0.84) including only studies performing a simultaneous three-way comparison and 0.86 (95%IC 0.81-0.90) considering only microbiologically confirmed studies. In the same analyses T-SPOT.TB sensitivity was 0.67 (95%IC 0.62-0.73); 0.76 (95%CI: 0.68 to 0.83); and 0.79 (95%IC 0.69-0.87), respectively. In low income countries QFT-G-IT pooled sensitivity was significantly lower: 0.57 (95%IC:0.52-0.61), considering all the studies, and 0.66 (95%IC 0.55-0.76) considering only microbiologically confirmed cases; while T-SPOT.TB sensitivity was 0.61 (95%IC 0.57-0.65) overall, but reached 0.80 (95%IC 0.73-0.86) in microbiologically confirmed cases. In microbiologically confirmed cases TST sensitivity was similar: 0.86 (95%IC 0.79-0.91) in high income countries, and 0.74 (95%IC 0.68-0.80) in low income countries. Higher IGRAs specificity with respect to TST was observed in high income countries (97-98% vs. 92%) but not in low income countries (85-93% vs. 90%).ConclusionsBoth IGRAs showed no better performance than TST in low income countries.

The usefulness of interferon-gamma release assay for diagnosis of tuberculosis-related uveitis in Korea.

PurposeTo evaluate the usefulness of the interferon-gamma release assay (IGRA) for diagnosing tuberculosis (TB)-related uveitis (TRU).MethodsRecords from 181 patients with ocular signs and symptoms suggestive of TRU and intraocular inflammation of unknown etiology were reviewed. All subjects underwent clinical and laboratory testing, including IGRA, to rule out presence of underlying disease. A diagnosis of presumed TRU was made based on an internist's TB diagnosis and a patient's response to anti-TB therapy. Sensitivity, specificity, and positive predictive values of IGRA for TRU diagnosis were calculated. Clinical characteristics were compared between patients with positive and negative IGRA results.ResultsThe sensitivity and specificity of IGRA for TRU were 100% and 72.0%, respectively. Mean age, percentage of patients with retinal vasculitis, and the anatomic type of uveitis were significantly different between patients with positive and negative IGRA results (all p ≤ 0.001). Positive IGRA rates and false-positive rates were significantly different between age and anatomic type groups (both p = 0.001). The positive predictive value of the IGRA among patients with intraocular inflammation was high (70%) when all of younger age (≤40 years), posterior uveitis, and retinal vasculitis were present.ConclusionsThe IGRA is useful for diagnosing TRU in the Korean population, especially when it is used as a screening test. Clinical characteristics, including younger age (≤40 years), posterior uveitis, and retinal vasculitis in IGRA-positive patients, increase the likelihood of the patient having TRU.

Interferon-gamma release assays for diagnosis of latent tuberculosis infection

Interferon-gamma release assays for diagnosis of latent tuberculosis infection

Interferon-gamma release assays for diagnosis of latent tuberculosis infection: evidence in immune-mediated inflammatory disorders

To provide a narrative synthesis of evidence on interferon-gamma release assays (IGRAs) for the diagnosis of latent tuberculosis infection (LTBI) in individuals with immune-mediated inflammatory disorders (IMIDs). Only a few studies have evaluated IGRAs in IMIDs, and most were small and varied considerably with respect to the use of immunosuppressive medications and types of IMIDs. Current evidence does not clearly suggest that IGRAs are better than tuberculin skin test (TST) in identifying individuals with IMID who could benefit from LTBI treatment. To date, no studies have been done on the predictive value of IGRAs in IMID patients. Important questions remain unanswered as to the impact of immunosuppressive medications and the impact of type of IMID on IGRA performance. Despite the lack of clear evidence, there is an increasing tendency for guidelines to prefer IGRA over TST in IMIDs or to recommend both TST and IGRA to enhance sensitivity. We believe the use of either test is acceptable for LTBI screening. Clinicians could consider starting with IGRAs in individuals with a history of Bacille Calmette-Guérin (BCG) vaccination after infancy or with repeated BCG vaccinations. When the index of suspicion for LTBI is high, both IGRA and TST could be performed, especially prior to initiating TNF-α inhibitor therapy. Regardless of the test used, it is important to remember that in the face of immune-suppression, both IGRA and TST can be falsely negative and are thus only diagnostic aids - they will need to be interpreted with other clinical and risk factor data.

Usefulness of Interferon-Gamma Release Assay for Diagnosis of Tuberculous Fistulae in Ano

Purpose: Interferon gamma release assays (QuantiFERON-TB Gold in Tube test [QFT-GIT]); Cellestis Limited, Victoria, Australia) have been studied for diagnosing pulmonary tuberculosis (TB) or latent TB but there have been no reports on the usefulness of this assay in diagnosing tuberculous anal fistula in actual clinical practices. In this study, we evaluated its diagnostic usefulness in patients with suspected tuberculous anal fistula. Methods: We conducted a retrospective analysis of 119 patients with suspected tuberculous anorectal fistula from May 2007 to May 2009. Diagnosis of tuberculous fistula was concluded by identification of acid-fast bacilli, typical caseating granuloma and successful clinical response to anti-TB chemotherapy. All patients underwent the QFT-GIT and all patients diagnosed with tuberculous anal fistula were analyzed. Results: Of the 119 patients with suspected TB fistula, 51 (43%) patients were classified as having TB fistula, including 31 with confirmed tuberculosis and 20 with probable tuberculosis, and other 68 (57%) were classified as not having tuberculosis. Among the 51 patients with TB fistula, Chronic caseating granuloma, acid-fast bacilli stain, and successful clinical response to anti-TB treatment were positive in 27 (52.9%), 4 (7.8%), and 20 (39.2%), respectively. Of the 51 with TB fistula, 44 had positive QFT-GIT results and 7 had negative results. The sensitivity and specificity of the assay were 86% and 85%, and positive predictive value (PPV) and negative predictive value (NPV) were 81% and 89%, respectively. Conclusion: QFT-GIT is a simple, sensitive, and specific method for the diagnosis of clinically highly suspected TB fistula.

Usefulness of the whole-blood interferon-gamma release assay for diagnosis of extrapulmonary tuberculosis

The whole-blood interferon-gamma enzyme-linked immunosorbent assay (QuantiFERON-TB Gold [QFT-G]; Cellestis, Carnegie, Australia) has been studied mainly for diagnosing active pulmonary tuberculosis (TB) or latent TB. We prospectively evaluated its diagnostic usefulness in patients suspected with extrapulmonary TB (EP-TB). Of the 100 adult patients with suspected EP-TB, 43 were classified as “confirmed” EP-TB and 5 as “probable” EP-TB. Of the 48 with EP-TB, 27 (56%) were diagnosed with TB lymphadenitis and 11 (17%) with skeletal TB. The overall sensitivity and specificity of the assay were 69% (95% confidence interval [CI 95], 53–81%) and 82% (CI 95, 69–91%), respectively. Among 44 patients presented with cervical lymphadenopathy, the QFT-G assay showed 86% (CI 95, 64–97%) sensitivity and 87% (CI 95, 66–97%) specificity, whereas in 28 with skeletal involvement, the sensitivity and specificity of the assay were 45% (CI 95, 17–77%) and 81% (CI 95, 54–96%), respectively. These suboptimal diagnostic performances suggest that the QFT-G assay alone is not sufficient for the diagnosis of EP-TB.