Role Of Interferon-gamma Release Assays Research Articles

Role of interferon-gamma release assay for screening and monitoring of latent tuberculosis infection in kidney transplant recipients

BackgroundThe reactivation of tuberculosis (TB) among kidney transplant (KT) recipients in an endemic area is of general concern. However, the epidemiology of latent TB infection (LTBI) status and its dynamic change responses have not been explored.MethodsBetween September 2020 and August 2021, a prospective study was conducted to investigate the status of LTBI in KT recipients who received a 9-month isoniazid universal prophylaxis. This status was measured using the interferon-gamma release assay (IGRA) with T-SPOT.TB before transplant, as well as at one month and nine months post-transplant.ResultsNinety-one KT recipients had a mean (SD) age of 45 (11) years, and 41% were female. Sixty-eight (75%) patients received a deceased donor allograft, and eighty-six (91%) patients received induction immunosuppressive therapy. The IGRA results were positive, borderline, negative, and indeterminate in 14 (15.4%), 6 (6.6%), 64 (70.3%), and 7 (7.8%) patients, respectively. Among 84 evaluable patients, 20 (23.8%) KT recipients were defined as having LTBI. Older age was significantly associated with LTBI (OR 1.06 [95% CI 1.01–1.12], p = 0.03). Among the 77 KT recipients who completed monitoring, 55 had negative IGRA results. Three (5.4%) KT recipients had conversion post-transplant. One of them developed pulmonary TB at 1 week after the transplant. Among the 13 patients with positive results, 8 (61.5%) remained positive, 1 (7.7%) had an indeterminate result at 1-month post-transplant and subsequently tested positive at 9 months post-transplant, and 4 (30.8%) experienced reversion to negative results throughout the study.ConclusionsIn a high TB-endemic area, one-quarter of KT recipients were reported to have LTBI, and the dynamic change of IGRA response in KT recipients is plausible post-transplant.

Role of Interferon-Gamma Release Assay for the Diagnosis and Clinical Follow up in Ocular Tuberculosis

ABSTRACT Purpose To assess the performance of interferon-gamma release assay (IGRA) associated with tuberculosis skin test (TST) for ocular tuberculosis (OTB) diagnosis and therapeutic decision making. Method One hundred and ninety-one patients with ocular inflammation were prospectively followed-up. Patients with clinical signs highly suspected of OTB, TST≥10 mm, and/or IGRA≥0.35 IU/mL received antitubercular therapy (ATT). Sensitivity (Se), specificity (Sp), and area under the curve (AUC) were assessed. Results Seventy-two (37.7%) patients received ATT for presumed OTB. Combining TST and IGRA had Se=89.6%, Sp=99.2%, and AUC (0.98) significantly higher compared to TST (0.85, Z=6.3, p<.001) or IGRA (0.95, Z=2.5, p=.01). Prior history of corticosteroids or immunosuppressant with concomitantly oral prednisone and baseline IGRA> 2.0 IU/mL was associated significantly with more recurrences in ATT patients (p=.01) . Conclusion Considering TST and IGRA together was more effective in assessing OTB diagnosis. The real value of the IGRA test to predict recurrences needs further studies.

TB or Not TB: Role of Interferon-Gamma Release Assays

Research Article| August 01 2021 TB or Not TB: Role of Interferon-Gamma Release Assays AAP Grand Rounds (2021) 46 (2): 19. https://doi.org/10.1542/gr.46-2-19 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation TB or Not TB: Role of Interferon-Gamma Release Assays. AAP Grand Rounds August 2021; 46 (2): 19. https://doi.org/10.1542/gr.46-2-19 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search nav search search input Search input auto suggest search filter All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: interferon type ii, tuberculosis, interferon gamma release assay, lymphadenitis Source: Martínez-Planas A, Baquero-Artigao F, Santiago B, et al. On behalf of the Spanish Pediatric TB Research Network (pTBred) and the European NontuberculouS MycoBacterial Lymphadenitis in childrEn (ENSeMBLE) study. Interferon-gamma release assays differentiate between Mycobacterium avium complex and tuberculous lymphadenitis in children [published online ahead of print May 10, 2021]. J Pediatr. doi. https://doi.org/10.1016/j.jpeds.2021.05.008 Investigators from multiple institutions conducted a study to assess the utility of interferon-gamma release assays (IGRAs) to differentiate tuberculosis (TB) from Mycobacterium avium complex (MAC) as the etiology of subacute/chronic submandibular/cervical lymphadenitis in children. Patients <18 years old with TB lymphadenitis who were included in the Spanish Network for the Study of Pediatric TB (pTBred) database between 2013 and 2018 were eligible for the current study. pTBred is a collaborative network of healthcare professionals in Spain; a central database includes demographic, laboratory test, and clinical data on children with TB.... You do not currently have access to this content.

Interferon-gamma release assays and the diagnosis of tuberculosis: have they found their place?

Tuberculosis (TB) remains an important issue in Australia with more than 85% of active cases contributed by overseas-born persons. Other risk groups include older Australians who acquired TB in the past and indigenous people. Immune suppression is an emerging risk factor for TB, particularly due to the expanding group of conditions for which potent immunosuppressive therapies is now used. Screening for latent TB is recommended in many risk groups including recent contacts of those with transmissible TB, those undergoing immune suppressive therapy, recently arrived refugees or migrants from high-risk countries and indigenous people with high rates of TB in the local community. Interferon-gamma release assay (IGRA) has now been available for several years for the diagnosis of latent TB. It is now used in many clinical situations, and despite the rapid rate of new publications, there are still gaps in our knowledge. This paper reviews the current role of interferon-gamma release assay in various situations, to determine its place in current practice and to explore where uncertainties exist.

Screening for latent tuberculosis in Norwegian health care workers: high frequency of discordant tuberculin skin test positive and interferon-gamma release assay negative results

BackgroundTuberculosis (TB) presents globally a significant health problem and health care workers (HCW) are at increased risk of contracting TB infection. There is no diagnostic gold standard for latent TB infection (LTBI), but both blood based interferon-gamma release assays (IGRA) and the tuberculin skin test (TST) are used. According to the national guidelines, HCW who have been exposed for TB should be screened and offered preventive anti-TB chemotherapy, but the role of IGRA in HCW screening is still unclear.MethodsA total of 387 HCW working in clinical and laboratory departments in three major hospitals in the Western region of Norway with possible exposure to TB were included in a cross-sectional study. The HCW were asked for risk factors for TB and tested with TST and the QuantiFERON®TB Gold In-Tube test (QFT). A logistic regression model analyzed the associations between risk factors for TB and positive QFT or TST.ResultsA total of 13 (3.4%) demonstrated a persistent positive QFT, whereas 214 (55.3%) had a positive TST (≥ 6 mm) and 53 (13.7%) a TST ≥ 15 mm. Only ten (4.7%) of the HCW with a positive TST were QFT positive. Origin from a TB-endemic country was the only risk factor associated with a positive QFT (OR 14.13, 95% CI 1.37 - 145.38, p = 0.026), whereas there was no significant association between risk factors for TB and TST ≥ 15 mm. The five HCW with an initial positive QFT that retested negative all had low interferon-gamma (IFN-γ) responses below 0.70 IU/ml when first tested.ConclusionsWe demonstrate a low prevalence of LTBI in HCW working in hospitals with TB patients in our region. The “IGRA-only” seems like a desirable screening strategy despite its limitations in serial testing, due to the high numbers of discordant TST positive/IGRA negative results in HCW, probably caused by BCG vaccination or boosting due to repetitive TST testing. Thus, guidelines for TB screening in HCW should be updated in order to secure accurate diagnosis of LTBI and offer proper treatment and follow-up.

Combined use of a TST and the T-SPOT®.&lt;I&gt;TB&lt;/I&gt; assay for latent tuberculosis infection diagnosis before anti-TNF-α treatment

Diagnosis of latent tuberculosis infection (LTBI) before anti-tumour-necrosis factor (anti-TNF) treatment is important. However, the tuberculin skin test (TST) has limitations, and the role of interferon-gamma release assays has not yet been determined. To evaluate the combined use of TST and the T-SPOT(®).TB (T-SPOT) assay prior to anti-TNF treatment. From July 2004 to March 2008, 281 patients were treated with anti-TNF agents. TST and T-SPOT were performed simultaneously at baseline. LTBI was defined as a positive TST of ≥10 mm induration or as a positive T-SPOT if TST was ≥5 mm but <10 mm. LTBI treatment was initiated, and patients were followed until August 2010. Positivity rates for TST and T-SPOT were respectively 33.6% (94/280) and 69.1% (186/269). LTBI treatment was initiated in 35.9% (101/281) of the patients, and active TB developed in 2.1% (6/281). Among the six TB patients, three were TST-negative at baseline and received no LTBI treatment, whereas all four who underwent T-SPOT showed positive results at baseline. In a TB-prevalent country, TST-defined LTBI diagnosis and treatment seem to be limited in preventing the development of TB before anti-TNF treatment. Further studies for T-SPOT alone or the combined use of TST and T-SPOT (either test positive strategy) for detecting LTBI are necessary.

Interferon-γ Release Assays for the Diagnosis of Mycobacterium Tuberculosis Infection in Children: A Literature Review

The role of interferon-gamma release assays (IGRAs) for immunologic diagnosis of tuberculosis in children is under debate. We carried out a narrative review on the studies on IGRAs in paediatric populations. A literature search was conducted using multiple keywords and standardized terminology in Medline, EMBASE and Cochrane databases, up to January 27th, 2011. Study quality was assessed using the MOOSE checklist and results of relevant studies were summarized. Sixty-seven paediatric studies (study population ranging from 14 to 5,244 children) were identified. Non-commercial ELISPOT assay (by means of ESAT-6 and CFP-10 antigens) had been carried out in 11 studies. QuantiFERON-TB Gold (QFT-G), QuantiFERON-TB Gold In-tube (QFT-G-IT), and T-SPOT.TB assays had been performed in 10, 44 and 18 studies, respectively. Most studies reported higher specificity of IGRA than tuberculin skin test (TST), but interpretation of the results is complicated by the fact that a gold standard for the diagnosis of latent TB is lacking. The reported sensitivity for active TB ranged from 51-93 percent for QFT-G/QFT-G-IT and 40-100 percent for ELISPOT assays, suggesting that a negative IGRA result may not exclude tuberculosis. Combining TST and IGRA results increased the diagnostic sensitivity. Rates of indeterminate results largely varied (0 to 35 percent). Most of the studies on young (less than 5 years) or immune-compromised children reported a proportion of indeterminate results exceeding 4 percent. Agreement among TST and IGRA, assessed by the k statistics, ranged from -0.03 to 0.87. Higher rates of discordance were reported in BCG-vaccinated than in non-BCG-vaccinated children. Studies on children less than 5 years and immunocompromised children reported conflicting results, as did studies on serial IGRA determinations. Despite the large amount of literature data, the role of IGRA in the pediatric population is still unclear, especially in young children. Combined use of TST/IGRA may increase diagnostic sensitivity but interpretation of discordant results remains a challenging issue.

The Role of Interferon-gamma Release Assay in Tuberculosis Control

Tuberculosis is still one of the major global public health threats. Countries with low incidence must focus on exhausting the reservoir of future cases by preventing reactivation. Therefore, it is important to identify and effectively treat those individuals who have latent tuberculosis infection and who may develop active disease. The tuberculin skin test has been the standard for detection of immune response against M. tuberculosis since the beginning of the 20th century. The new millennium has brought advancement in the diagnosis of latent tuberculosis infection. The name of the new blood test is interferon-gamma release assay (IGRA). Croatia is a middle-incidence country with a long decreasing trend and developed tuberculosis control. To reach low incidence and finally eliminate tuberculosis, its tuberculosis programme needs a more aggressive approach that would include intensive contact investigation and treatment of persons with latent tuberculosis infection. This article discusses the current uses of IGRA and its role in tuberculosis control.

Interferon‐Gamma Release Assays Are a Better Tuberculosis Screening Test for Hemodialysis Patients: A Study and Review of the Literature

Diagnosing latent tuberculosis (TB) infection (LTBI) in dialysis patients is complicated by poor response to tuberculin skin testing (TST), but the role of interferon-gamma release assays (IGRAs) in the dialysis population remains uncertain. Seventy-nine patients were recruited to compare conventional diagnosis (CD) with the results of two IGRA tests in a dialysis unit. Combining TST, chest x-ray and screening questionnaire results (ie, CD) identified 24 patients as possible LTBI. IGRA testing identified 22 (QuantiFERON Gold IT, Cellestis, USA) and 23 (T-spot.TB, Oxford Immunotec, United Kingdom) LTBI patients. IGRA and CD correlated moderately (κ=0.59). IGRA results correlated with history of TB, TB contact and birth in an endemic country. TST was not helpful in identifying LTBI patients in this population. The tendency for IGRAs to correlate with risk factors for TB, active TB infection and history of TB argues for their superiority over TST in dialysis patients. There was no superiority of one IGRA test over another.

Role of interferon-gamma release assays (IGRAs) for the screening of latent tuberculosis infection in patients candidates for TNF-α antagonist

Background: Tumor necrosis factor-α (TNF-a) inhibitors are associated with an increased risk of reactivation of latent tuberculosis infection (LTBI); thus, the guidelines recommends TB screening for all patients before starting anti-TNF-α therapy.The use of tuberculin skin test (TST) is controversial because of the immunosuppressive treatment may lead to false-negative TST results and previous BCG-vaccination produces false-positive. The introduction in clinical practice of the interferon-gamma release assays (IGRAs) has opened new perspectives for diagnosis of LTBI.The aim of the study was to investigate the performance of QuantiFERON-TB Gold In Tube assay (QFT-GIT) for the diagnosis of LTBI in patients with an immune-mediated inflammatory diseases candidates for anti-TNF-α therapy. Methods:We enrolled 195 patients with rheumatoid arthritis (n=72), psoriatic arthritis (n=40), psoriasis (n=41), ankylosing spondylitis (n=10), Crohn’s disease (n=18), and Behcet’s disease (n=8). Screening included: clinical evaluation, chest X-ray,TST and QFT-GIT. Results: Of the 195 patients, 32 (16.4%), 137 (70.2%) and 26 (13.3%) tested positive, negative and indeterminate with QFT-GIT test, respectively. The level of agreement between two tests was 81.6 % (k=0.55). Among the screened patients, 38 (19%) were considered to have LTBI and received isoniazid treatment, while 31 patients (16%) showed discordant results between two tests. Univariate analysis showed an association between BCG vaccination and discordant TST-positive/QFT-GIT-negative results (OR=6; 95%CI: 2.3-37.1; p&lt;0.001); no association was observed between the immunosuppressive therapy and discordant TST-negative/QFT-GIT-positive results (OR=0.16; 95%CI: 0.01-1.8; p&lt;0.09). Conclusions: Our results suggest that QFT-GIT may be helpful for the diagnosis of LTBI in patients candidates for anti-TNF-α treatment because of its performance seems to not be affected by any type of immunosuppression.

Role of interferon-gamma release assays in the diagnosis of pulmonary tuberculosis in patients with advanced HIV infection

BackgroundT-cell interferon-gamma release assays (IGRAs) may have a role in the diagnosis of active tuberculosis when evaluating patients for whom standard microbiology has limited sensitivity. Our objective was to examine the accuracy of a commercial IGRA for diagnosis of active tuberculosis in HIV-infected persons.MethodsWe enrolled HIV-infected patients admitted to Mulago Hospital in Kampala, Uganda with cough ≥ 2 weeks. All patients underwent standard medical evaluation. We collected peripheral blood specimens at enrollment and performed a commercial, ELISPOT-based IGRA according to the manufacturer's recommendations. IGRA sensitivity and specificity were determined using mycobacterial culture results as the reference standard.ResultsOverall, 236 patients were enrolled. The median CD4+ T-lymphocyte count was 49 cells/μl and 126 (53%) patients were diagnosed with active pulmonary tuberculosis. IGRAs were not performed in 24 (10%) patients due to insufficient mononuclear cell counts. In the remaining 212 patients, results were indeterminate in 54 (25%). IGRAs were positive in 95 of 158 (60%) patients with interpretable results. The proportion of positive test results was similar across CD4+ count strata. IGRA sensitivity was 73% and specificity 54%. IGRA results did not meaningfully alter the probability of active tuberculosis in patients with negative sputum smears.ConclusionsAn ELISPOT-based IGRA detected a high prevalence of latent tuberculosis infection in a hospitalized population of tuberculosis suspects with advanced HIV/AIDS but had limited utility for diagnosis of active tuberculosis in a high prevalence setting. Further research is needed to identify stronger and more specific immune responses in patients with active tuberculosis.

Interferon gamma release assays: principles and practice

The last decade has witnessed significant advances in mycobacterial genomics and cellular research which have resulted in the development of two new blood tests, the enzyme-linked immunospot assay (ELISpot) (TSPOT.TB, Oxford Immunotec, Oxford, UK) and the enzyme-linked immunosorbent assay (ELISA) (QuantiFERON-TB Gold In-Tube, Cellestis, Carnegie, Australia). These tests, which are collectively known as interferon gamma release assays (IGRAs), detect latent tuberculosis infection (LTBI) by measuring interferon (IFN)-gamma release in response to antigens present in Mycobacterium tuberculosis, but not bacille Calmette-Guerin (BCG) vaccine and most nontuberculous mycobacteria. This is done through enumeration of IFN-gamma-secreting T cells (ELISpot) or by measurement of IFN-gamma concentration (ELISA). The evidence base for these tests has expanded rapidly and now demonstrates that IGRAs are more specific than the tuberculin skin test (TST) as they are not confounded by previous BCG vaccination. In addition, with active tuberculosis (TB) as a surrogate for LTBI, it appears that the ELISA has a similar sensitivity to the TST, whereas the ELISpot is more sensitive. Using degree of exposure to TB as a surrogate for LTBI, both assays correlate at least as well with TB exposure as the TST. Recent longitudinal data have now demonstrated the prognostic power of positive IGRA results in recent contacts for the subsequent progression to active TB. Deployment of IGRAs, driven by new guidelines internationally, will impact on clinical practice in several ways. Their high specificity means that BCG-vaccinated individuals with a false-positive TST will not receive unnecessary preventive treatment, whereas improved sensitivity in individuals with weakened cellular immunity at highest risk of progressing to active TB (for example HIV-positive individuals) enables more reliable targeted testing and treatment of these vulnerable groups. The role of IGRAs in active TB is less clear but they may be useful as adjunctive tests in the diagnostic work-up of an individual with suspected TB. Finally, recent developments and future directions in IGRA development are reviewed.

Answers linked to Swindells JE, Aliyu SH, Enoch DA, Abubakar I. The role of interferon gamma-release assays in healthcare workers. J Hosp Infect 2009; 73: 101–108

Answers linked to Swindells JE, Aliyu SH, Enoch DA, Abubakar I. The role of interferon gamma-release assays in healthcare workers. J Hosp Infect 2009; 73: 101–108

Questions linked to Swindells JE, Aliyu SH, Enoch DA, Abubakar I. The role of interferon gamma-release assays in healthcare workers. J Hosp Infect 2009; 73:101–108.

Questions linked to Swindells JE, Aliyu SH, Enoch DA, Abubakar I. The role of interferon gamma-release assays in healthcare workers. J Hosp Infect 2009; 73:101–108.