IGRA Results Research Articles

CD27 expression of T-cells discriminates IGRA-negative TB patients from healthy contacts in Ghana

IFN-γ release assays (IGRAs) have suboptimal sensitivity for detection of Mycobacterium tuberculosis (Mtb) infection and cannot discriminate between tuberculosis (TB) patients and healthy -potentially Mtb infected- contacts (HCs). In a case-control study, we determined T-cell phenotypes of IGRAs in TB patients (n = 20) and HCs (n = 20) from Ghana. CD27 expression of T-cells was significantly lower in TB patients as compared to HCs independent from Mtb-specificity. CD27 expression discriminated both study groups - including TB patients with low or indeterminate IGRA results - effectively. We conclude that CD27 is a promising biomarker for diagnosis of TB patients with inconclusive IGRA results.

Tuberculosis screening among healthcare workers in Sicily, Italy.

Tuberculosis (TB) is a diffuse communicable disease; and healthcare workers (HCWs) are among the at-risk populations for the disease. This study reports the result of TB surveillance in HCWs operating in three hospitals: one classified as 'low' risk for TB and two as 'medium' risk. A total of 2228 HCWs underwent TB screening using the standard Mantoux technique (also known as the tuberculin sensitivity test [TST]). Interferon-γ release assay (IGRA) was carried out in TST-positive subjects. Results showed an overall positivity of 21% to TST and 2% to IGRA test. TST and IGRA results were statistically associated with HCWs born after 1981. This result is due to university policies that highly recommend TB immunization. Data support the use of IGRA assay in TST-positive HCWs, in order to identify latent TB infection from vaccination.

Screening and treatment for tuberculosis in a cohort of unaccompanied minor refugees in Berlin, Germany.

IntroductionIn 2015, 4062 unaccompanied minor refugees were registered in Berlin, Germany. According to national policies, basic clinical examination and tuberculosis (TB) screening is a prerequisite to admission to permanent accommodation and schooling for every refugee. This article evaluates the use of an interferon-γ-release-assay (IGRA) during the initial examination and TB screening of 970 unaccompanied minor refugees.ResultsIGRA test were obtained during TB screening for 301 (31.0%) of 970 adolescents not previously screened for TB. Positive IGRA results were obtained in 13.9% (42/301). Most of the 42 IGRA-positive refugees originated from Afghanistan or Syria (n?20 and 10 respectively). Two IGRA-positive adolescents were lost to follow-up, 2 were diagnosed with TB and the remaining 38 diagnosed with latent TB infection (LTBI). Demographic features of the 40 patients with positive IGRA result were as follows: 39 male, median age 16.8 years (IQR 16.0–17.2y), none meeting underweight criteria (median BMI 21.3kg/m2). On initial chest X-ray 2/40 participants had signs of active TB, while in 38 active disease was excluded and the diagnosis of latent TB infection (LTBI) made. Active hepatitis B-co-infection was diagnosed in 3/38 patients. All patients with LTBI received Isoniazid and Rifampicin for 3 months without occurrence of severe adverse events. The most frequently observed side effect was transient upper abdominal pain (n = 5). Asymptomatic elevation of liver transaminases was seen in 2 patients. 29 patients completed treatment with no signs of TB disease at the end of chemoprevention and 9 were lost to follow up.ConclusionScreening for TB infection in minor refugees was feasible in our setting with a relatively high rate of TB infection detected. Chemopreventive treatment was tolerated well regardless of underlying hepatitis-B-status. Minor refugees migrating to Germany should be screened for TB infection, instead of TB disease only, regardless of the background TB incidence.

Interferon gamma release assays for Diagnostic Evaluation of Active tuberculosis (IDEA): test accuracy study and economic evaluation

Interferon gamma release assays (IGRAs) are blood tests recommended for the diagnosis of tuberculosis (TB) infection. There is currently uncertainty about the role and clinical utility of IGRAs in the diagnostic workup of suspected active TB in routine NHS clinical practice. To compare the diagnostic accuracy and cost-effectiveness of T-SPOT.TB ® (Oxford Immunotec, Abingdon, UK) and QuantiFERON® TB GOLD In-Tube (Cellestis, Carnegie, VIC, Australia) for diagnosis of suspected active TB and to estimate the diagnostic accuracy of second-generation IGRAs. Prospective within-patient comparative diagnostic accuracy study. Secondary care. Adults (aged ≥ 16 years) presenting as inpatients or outpatients at 12 NHS hospital trusts in London, Slough, Oxford, Leicester and Birmingham with suspected active TB. The index tests [T-SPOT.TB and QuantiFERON GOLD In-Tube (QFT-GIT)] and new enzyme-linked immunospot assays utilising novel Mycobacterium tuberculosis antigens (Rv3615c, Rv2654, Rv3879c and Rv3873) were verified against a composite reference standard applied by a panel of clinical experts blinded to IGRA results. Sensitivity, specificity, predictive values and likelihood ratios were calculated to determine diagnostic accuracy. A decision tree model was developed to calculate the incremental costs and incremental health utilities [quality-adjusted life-years (QALYs)] of changing from current practice to using an IGRA as an initial rule-out test. A total of 363 patients had active TB (culture-confirmed and highly probable TB cases), 439 had no active TB and 43 had an indeterminate final diagnosis. Comparing T-SPOT.TB and QFT-GIT, the sensitivities [95% confidence interval (CI)] were 82.3% (95% CI 77.7% to 85.9%) and 67.3% (95% CI 62.1% to 72.2%), respectively, whereas specificities were 82.6% (95% CI 78.6% to 86.1%) and 80.4% (95% CI 76.1% to 84.1%), respectively. T-SPOT.TB was more sensitive than QFT-GIT (relative sensitivity 1.22, 95% CI 1.14 to 1.31; p < 0.001), but the specificities were similar (relative specificity 1.02, 95% CI 0.97 to 1.08; p = 0.3). For both IGRAs the sensitivity was lower and the specificity was higher for human immunodeficiency virus (HIV)-positive than for HIV-negative patients. The most promising novel antigen was Rv3615c. The added value of Rv3615c to T-SPOT.TB was a 9% (95% CI 5% to 12%) relative increase in sensitivity at the expense of specificity, which had a relative decrease of 7% (95% CI 4% to 10%). The use of current IGRA tests for ruling out active TB is unlikely to be considered cost-effective if a QALY was valued at £20,000 or £30,000. For T-SPOT.TB, the probability of being cost-effective for a willingness to pay of £20,000/QALY was 26% and 21%, when patients with indeterminate test results were excluded or included, respectively. In comparison, the QFT-GIT probabilities were 8% and 6%. Although the use of IGRAs is cost saving, the health detriment is large owing to delay in diagnosing active TB, leading to prolonged illness. There was substantial between-patient variation in the tests used in the diagnostic pathway. The recruitment target for the HIV co-infected population was not achieved. Although T-SPOT.TB was more sensitive than QFT-GIT for the diagnosis of active TB, the tests are insufficiently sensitive for ruling out active TB in routine clinical practice in the UK. Novel assays offer some promise. The novel assays require evaluation in distinct clinical settings and in immunosuppressed patient groups. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and the NIHR Health Protection Research Unit in Respiratory Infections, Imperial College London, London, UK.

Interferon Gamma Release Assays in Patients with Respiratory Isolates of Non-Tuberculous Mycobacteria - a Preliminary Study.

Interferon gamma releasing assays (IGRAs) are extensively used in the diagnosis of latent tuberculosis infections. Comparing to tuberculin skin test (TST) they lack false positive results in the populations vaccinated with BCG, and in most non-tuberculous mycobacteria (NTM) infections. Nevertheless, Mycobacterium kansasii, Mycobacterium marinum, and Mycobacterium szulgai may induce positive IGRAs due to RD1 homology with Mycobacterium tuberculosis. The aim of the study was to investigate the possible influence of NTM respiratory isolates on the results of IGRAs. 39 patients (23 females and 16 males) of median age 61 years, with negative medical history concerning tuberculosis, entered the study. Identification of NTM was performed using the niacin test and molecular method GenoType CM test (Hain Lifescience). QFT-Plus was performed in 17 patients, T-SPOT-Tb – in 23 patients. Chest X-rays and a high-resolution computed tomography of the chest have been reviewed by the experienced radiologist blinded to the results of IGRAs, in search of past tuberculosis signs. Positive IGRAs results were obtained in three out of 39 patients (8%): 22% of patients with M. kansasii isolates and 18% of patients with radiological signs on HRCT that might be suggestive of past tuberculosis. Positive IGRAs correlated with radiological signs suggestive of past tuberculosis (r = 0.32, p = 0.04), and on the borderline with isolation of M. kansasii (r = 0.29, p = 0.06). These findings may suggest that a positive IGRAs result, in our material, could depend mostly on asymptomatic past Tb infection. The cross-reactivity of M. kansasii isolates with IGRAs was less probable; nevertheless, it requires further investigations.

Factors Associated with False Negative Interferon-γ Release Assay Results in Patients with Tuberculosis: A Systematic Review with Meta-Analysis

Background: Although interferon-γ release assay (IGRA) is widely used for diagnosis of latent tuberculosis (TB) infection, which factors are related to false negative results are uncertain. The aim of this systematic review was to describe the risk factors associated with false negative IGRA results. Methods: Two authors independently identified studies designed to evaluate risk factors for false negative IGRA results from PubMed, the Cochrane Register of Control Trial database, and EMBASE assessed on October 22, 2018. Meta-analyses were conducted with random-effect models and heterogeneity was calculated with the I2 method. Findings: Of 1,377 titles and abstracts screened, 47 full texts were selected for review, and we finally included 17 studies in this systematic review. The most commonly studied risk factor (14 studies) was advanced age followed by low peripheral lymphocyte counts (7 studies), and these factors were associated with false negative results even under different TB prevalence (pooled odds ratio, 2.06; 95%CI, 1.68-2.52 in advanced age, and 7.93; 95%CI, 1.74-36.09 in low peripheral lymphocyte counts, respectively). However, detailed procedure of these assays were not clearly stated in many studies and the cut-off value of these factors were varied. Interpretation: Advanced age and low peripheral lymphocyte counts may be common risk factors for false negative IGRA results, suggesting people with these factors need careful followed-up even if they have negative IGRA results. Standardization of the assay procedure and assessment of risk factors with common definition and the same cut-off value are needed. Funding Statement: The authors state: There was no funding source for this study. Declaration of Interests: The authors declare declare no competing interests.

790. The Efficacy of the Interferon-γ Releasing Assay-Based Isoniazid Treatment for Preventing Active Tuberculosis in Kidney Transplant Recipients: A Quasi-experimental Study

BackgroundInterferon-γ releasing assays (IGRAs) are useful for diagnosing LTBI. However, there are limited data on the efficacy of IGRA-based isoniazid (INH) treatment with/without back-up tuberculin skin test (TST) to prevent the development of TB in solid-organ transplant recipients.MethodsAll adults patients admitted to a KT unit from January 2014 to December 2016 were retrospectively reviewed in a 2,700-bed, tertiary-care hospital in Seoul, South Korea. The IGRA (i.e., QuantiFERON-In-Tube) with/without TST was performed on all recipients before KT, and 9-month INH treatment was given to patients with clinical risk factors for LTBI regardless of IGRA results. Our hospital policy on LTBI diagnosis and treatment was changed as follows. Period 1 (January 2014–September 2015) adopted IGRA-based INH treatment. We administered INH treatment to all patients with positive IGRA results. Period 2 and period 3 adopted IGRA-based followed by back-up TST-based INH treatment. Period 2 (October 2015–December 2015) included the temporary shortage of Mantoux test, so INH treatment was not given to the patients with positive IGRA since back-up TST was not performed. In Period 3 (January 2016–December 2016), we administered INH treatment to the patients with positive IGRA results followed by back-up TST¡Ã10 mm. The development of TB after KT as the primary endpoint was observed from January 2014 to April 2018.ResultsThe study flow is shown in Figure 1. Of the 1,150 KT recipients, 14 (1.2%) developed TB (incidence rate 0.63 per 100 person-years, 95% CI 0.35–1.06). The median time for TB development was 9.4 months (IQR 4.7–14.5). Seven (3.2%) of 216 patients with positive IGRA without INH treatment developed TB, whereas none of 106 patients with positive IGRA with INH treatment developed TB (rate difference 2.43 per 100 person-years, P = 0.008) and 7 (0.8%) of 828 patients with negative or indeterminate IGRA results developed TB (rate difference 2.0 per 100 person-years, P < 0.001). The number needed to treat (NNT) for IGRA-based INH treatment was 31 (95% CI 18–114).ConclusionIGRA-based INH treatment is effective to prevent the development of TB in KT recipients without clinical risk factors for LTBI with reasonable NNT. Disclosures All authors: No reported disclosures.

789. Comparison of Interferon-γ Release Assays (IGRAs) for Diagnosis of Latent or Active Tuberculosis in Cancer Patients

BackgroundPatients with certain types of cancer are at increased risk for progression from latent tuberculosis infection (LTBI) to active tuberculosis (ATB) because of immunosuppression. The purpose of this study was to compare the utility of the two commonly used IGRAs, QuantiFERON-TB Gold® (QFT) and T-spot.TB® (T-spot.TB), for diagnosis of LTBI or ATB in cancer patients.MethodsWe identified patients who had an initial IGRA during 2013 and 2014 at our institution. Along with demographic information, collected clinical data included type of underlying cancer or other condition, reason for testing, diagnosis of ATB following testing, and absolute lymphocyte count (ALC) at the time of testing. IGRA results (positive, negative, borderline, or indeterminate/invalid) were compared between patients who underwent testing with either QFT or T-spot.TB.ResultsA total of 356 patients had 411 QFT tests done, while 737 patients had 853 T-spot.TB tests performed. The most common underlying malignancies in the QFT and T-spot.TB groups were acute myeloid leukemia (30% and 25%, respectively) and solid tumors (28% vs. 30%, respectively). The most common reasons for testing were pre-hematopoietic-cell transplantation (HCT) screening (42% with QFT and 31% with T spot.TB) or suspected pulmonary ATB (34% with QFT and 42% with T spot.TB). In the QFT group, 145/411 (35%) tests were indeterminate, while only 96/853 (11%) tests in the T-spot.TB group were invalid (P <0.001). The median ALC was 650 cells/µL in patients with an indeterminate result in the QFT group and 90 cells/µL in patients with an invalid test in the T-spot.TB group. A total of four patients were diagnosed with ATB at 1 year after testing. Figure 1 provides a flowchart describing IGRA testing results and development of ATB.ConclusionThe frequency of an inconclusive test result is significantly higher with QFT as compared with T-spot.TB for diagnosis of LTBI or ATB in cancer patients. A low ALC is likely a contributing factor in indeterminate QFT and invalid T spot.TBresults. Disclosures E. Ariza-Heredia, Oxford Immunotec: Grant Investigator, Research grant. R. F. Chemaly, Oxford Immunotec: Consultant and Grant Investigator, Research grant.

A Study of Optimal Screening for Latent Tuberculosis in Patients with Inflammatory Bowel Disease

Reactivation of LTBI in patients with IBD on anti-TNF-α agents can lead to serious life-threatening illness. No gold standard exists for the detection of LTBI. We examined whether a dual testing strategy with TST and IGRA would improve the detection of LTBI. Consecutive IBD patients being considered for anti-TNF-α treatment underwent testing with a TST, IGRA and CXR. All patients completed a self-administered questionnaire. The association of both tests with demographic factors, LTBI risk factors, BCG vaccination, IS therapy and agreement between the TST and IGRA were evaluated. One-hundred and fifty-five IBD patients were included, 6% were TST positive and 5% were IGRA positive. Concordance between TST and IGRA was fair (κ = 0.21, 95% CI - 0.081-0.498). Neither test was affected by age, gender or BCG vaccination. The presence of risk factors for LTBI was found to be positively associated with TST (OR 19.8, 95% CI 3.9-102.1), but not IGRA. IGRA was negatively associated with IS therapy (OR 0.06, 95% CI 0.007-0.5), but not TST. Four patients who were IGRA positive but TST negative were treated for LTBI by a respirologist. An IGRA result was negatively associated with IS therapy, while the presence of risk factors for LTBI was found to be positively associated with TST results. There was fair agreement between positive TST and IGRA results. The addition of IGRA to the standard practice of TST and CXR increased the number of cases that were initiated on LTBI therapy.

Prevalence of tuberculosis infection and disease in children referred for tuberculosis medical surveillance in Ontario: a single-cohort study.

There are few data about the utility of the Canadian tuberculosis medical surveillance system for detecting tuberculosis in children and adolescents. We sought to assess the prevalence of tuberculosis infection and disease in children and adolescents referred by the tuberculosis medical surveillance program who were evaluated at The Hospital for Sick Children (SickKids) tuberculosis program. We retrospectively studied clinical records, radiographic findings and results of interferon-γ release assays (IGRAs) of all children less than 18 years of age referred by the tuberculosis medical surveillance program and evaluated at SickKids between November 2012 and June 2016. The median age of the 216 children was 10.0 years. Most were born in the Philippines (157 [72.7%]) or India (39 [18.0%]). Of the 216, 166 (76.8%) had a history of prior treatment for tuberculosis, and 34 (15.7%) were federal-sponsored refugees from settings with a high tuberculosis burden. Negative IGRA results were found in 110/130 (84.6%) of those with prior tuberculosis treatment. Thirty-one children (14.4%) had any chest radiographic abnormality, of whom 4 had changes thought to be due to tuberculosis. No child received a diagnosis of active tuberculosis at assessment or during follow-up; 3 (1.4%) were treated for latent tuberculosis infection following IGRA testing at SickKids. A positive IGRA result was associated with contact with infectious tuberculosis (odds ratio [OR] 5.97, 95% confidence interval [CI] 2.06-17.52) and older age at first clinic visit (OR 2.98, 95% CI 1.24-8.30) but not with radiographic abnormalities or history of prior tuberculosis treatment. Most children were referred because of a history of prior treatment for tuberculosis; few had clinical or laboratory evidence of infection or prior disease. The tuberculosis medical surveillance process did not identify any children who required treatment for active disease and requires improvement.

Combined IFN-γ and TNF-α release assay for differentiating active tuberculosis from latent tuberculosis infection

The IFN-γ-release assay (IGRA) cannot differentiate active tuberculosis (TB) from latent TB infection (LTBI). We hypothesized that the TNF-α-release assay (TARA) combined with IGRA might discriminate active TB from not active TB without LTBI. Adult patients with suspected TB, and with unrelated diseases such as herpes zoster as controls, were enrolled in an intermediate TB-burden country. Patients with confirmed or probable TB were regarded as active TB, and patients with not active TB were further classified as those having not active TB with and without LTBI based on IGRA results. The IGRA and TARA by using ELISPOT assays were performed on peripheral mononuclear cells. Thirty six patients with active TB and 53 patients including 18 not active TB with LTBI and 35 not active TB without LTBI were finally included. The sensitivity and specificity of the IGRA for those patients found to have active TB were 94% (CI, 80-99) and 66% (CI 52-78), respectively. Combining the IGRA and the TARA substantially increased the specificity for active TB (93%, CI, 82-98; P = 0.001) compared with the IGRA only, without compromising sensitivity (89%, CI, 73-96; P = 0.67). Combining the IGRA and TARA appears to be useful for diagnosing active TB.

Prospective cross-sectional study of tuberculosis screening in United Arab Emirates

ObjectivesIntense migrations from tuberculosis endemic areas to Gulf countries create special risks for people in the region. The purpose of this study was to provide data that could justify implementing universal, regular TB screening in UAE. DesignThis prospective, cross-sectional study used interferon-γ release assay (IGRA) to screen for TB among Emirati citizens between August-2016 and May-2017; expatriates were not included in this study. Participants were recruited from Emiratis attending Tawam Hospital Polyclinics for problems unrelated to TB risk assessment. IGRA was requested for all enrolled participants. A risk-assessment questionnaire was completed by all participants. In addition, a retrospective review of IGRA results (January-2011 to April-2016) was conducted to compare prevalence of positive IGRA in the ‘prospective sample’ with that in ‘patients screened in the past’. ResultsFour hundred fifty-five participants (69% females) were enrolled in this study. Participants’ age (mean±SD) was 42±16y. The majority of participants had traveled to or had helpers from TB-endemic areas. Two hundred forty (53%) participants had IGRA test. Forty-five (18.8%) participants had positive IGRA, similar to the retrospective results of 12.4% to 23.5%. ConclusionsThe prevalence of positive-IGRA in this study is high.

Characteristics Associated with Negative Interferon-γ Release Assay Results in Culture-Confirmed Tuberculosis Patients, Texas, USA, 2013-2015.

Interferon-γ release assays (IGRAs) are the preferred diagnostic test for tuberculosis (TB) infection in at-risk populations in developed countries. However, IGRAs have high false-negative rates in patients with TB disease. Population-based studies assessing the factors associated with negative IGRA results in TB patients have not been performed. Using statewide TB surveillance data of culture-confirmed TB patients in Texas, USA, during 2013–2015, we describe the patient characteristics and treatment outcomes associated with false-negative IGRA results. Among 2,854 TB patients, 1,527 (53.5%) had an IGRA result; 97.4% (1,487/1,527) of those had a positive (87.7%) or negative (12.3%) result. Older age, HIV co-infection, non-Hispanic white race/ethnicity, and being tested with T-SPOT.TB were associated with negative IGRA results. TB patients with negative IGRA results had a higher mortality, potentially due to delayed treatment. Healthcare providers should consider these risk factors when making decisions for patients with suspected TB and negative IGRA results and potentially provide treatment.

Decreased ex vivo production of interferon-gamma is associated with severity and poor prognosis in patients with lupus

BackgroundLupus pathogenesis is closely associated with interferon gamma (IFN-γ), which plays a central role in innate and adaptive immunity. The aim of this study was to evaluate the ex vivo production of IFN-γ after stimulation of peripheral blood mononuclear cells with phytohemagglutinin (PHA) in patients with lupus, according to disease activity.MethodsThis study included 118 patients with lupus who had undergone IFN-γ-releasing assays (IGRAs) to screen for tuberculosis. Data on IFN-γ production in negative (nil) and positive (mitogen with PHA) controls were collected and analysed. The difference (mitogen minus nil) was used to calculate ex vivo IFN-γ production. Disease activity was evaluated using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K). Poor hospitalisation outcome was defined as in-hospital mortality or intensive care unit admission. Associations among disease activity, poor hospitalisation outcome, and ex vivo IFN-γ production were assessed.ResultsThe level of ex vivo IFN-γ production was significantly lower in patients with active systemic lupus erythematosus (SLE) (n = 64) than in those with inactive SLE (n = 54) (median 0.92 vs. 11.06 IU/mL, p < 0.001). Ex vivo IFN-γ production was correlated with the SLEDAI-2 K (r = − 0.587, p < 0.001). Results of multivariate logistic regression analysis showed that ex vivo IFN-γ production ≤ 7.19 IU/mL was an independent predictor for discriminating active and inactive lupus. In addition, patients with ex vivo IFN-γ production ≤ 0.40 IU/mL had more frequent poor hospitalisation outcomes than those with ex vivo IFN-γ production > 0.40 (40.0% vs. 9.3%, p = 0.001). The proportion of indeterminate IGRA results was higher in patients with active lupus than in those with inactive lupus (45.3% vs. 0.0%, p < 0.001) because of decreased ex vivo IFN-γ production.ConclusionsEx vivo IFN-γ production is a useful biomarker for assessing disease activity and predicting poor clinical outcomes of SLE.

Identification of new antigen candidates for the early diagnosis of Mycobacterium avium subsp. paratuberculosis infection in goats

Currently Mycobacterium avium subsp. paratuberculosis (MAP) infection is diagnosed through indirect tests based on the immune response induced by the infection. The antigens commonly used in IFN-γ release assays (IGRA) are purified protein derivative tuberculins (PPD). However, PPDs, lack both specificity (Sp) and sensitivity (Se) in the early phase of infection. This study investigated the potential of 16 MAP recombinant proteins and five lipids to elicit the release of IFN-γ in goats from herds with or without a history of paratuberculosis. Ten recombinant proteins were selected as potential candidates for the detection of MAP infection in young goats. They were found to detect 25 to 75% of infected shedder (IS) and infected non-shedder (INS) kids younger than 10months of age. In comparison, PPD was shown to detect only 10% of INS and no IS kids. For seven antigens, Se (21–33%) and Sp (≥90%) of IGRA were shown to be comparable with PPD at 20months old. Only three antigens were suitable candidates to detect IS adult goats, although Se was lower than that obtained with PPD. In paratuberculosis-free herds, IGRA results were negative in 97% of indoor goats and 86% of outdoor goats using the 10 antigens. However, 22 to 44% of one-year-old outdoor goats were positive suggesting that they may be infected. In conclusion, this study showed that ten MAP recombinant proteins are potential candidates for early detection of MAP infected goats. Combining these antigens could form a possible set of MAP antigens to optimize the Se of caprine IGRA.

Interferon Gamma Release Assays for Latent Tuberculosis: What Are the Sources of Variability?

Interferon gamma release assays (IGRAs) are blood-based tests intended for diagnosis of latent tuberculosis infection (LTBI). IGRAs offer logistical advantages and are supposed to offer improved specificity over the tuberculin skin test (TST). However, recent serial testing studies of low-risk individuals have revealed higher false conversion rates with IGRAs than with TST. Reproducibility studies have identified various sources of variability that contribute to nonreproducible results. Sources of variability can be broadly classified as preanalytical, analytical, postanalytical, manufacturing, and immunological. In this minireview, we summarize known sources of variability and their impact on IGRA results. We also provide recommendations on how to minimize sources of IGRA variability.

Usefulness of interferon-γ release assay for the diagnosis of latent tuberculosis infection in young children.

PurposeLatent tuberculosis infection (LTBI) in young children may progress to severe active tuberculosis (TB) disease and serve as a reservoir for future transmission of TB disease. There are limited data on interferon-γ release assay (IGRA) performance in young children, which our research aims to address by investigating the usefulness of IGRA for the diagnosis of LTBI.MethodsWe performed a tuberculin skin test (TST) and IGRA on children who were younger than 18 years and were admitted to Chung-Ang University Hospital during May 2011–June 2015. Blood samples for IGRA were collected, processed, and interpreted according to manufacturer protocol.ResultsAmong 149 children, 31 (20.8%) and 10 (6.7%) were diagnosed with LTBI and active pulmonary TB, respectively. In subjects lacking contact history with active TB patients, TST and IGRA results were positive in 41.4% (29 of 70) and 12.9% (9 of 70) subjects, respectively. The agreement (kappa) of TST and IGRA was 0.123. The control group, consisting of non-TB-infected subjects, showed no correlation between age and changes in interferon-γ concentration after nil antigen, TB-specific antigen, or mitogen stimulation in IGRAs (P=0.384, P=0.176, and P=0.077, respectively). In serial IGRAs, interferon-γ response to TB antigen increased in IGRA-positive LTBI subjects, but did not change considerably in initially IGRA-negative LTBI or control subjects.ConclusionThe lack of decrease in interferon-γ response in young children indicates that IGRA could be considered for this age group. Serial IGRA tests might accurately diagnose LTBI in children lacking contact history with active TB patients.

Effect of immunosuppressive therapy on interferon γ release assay for latent tuberculosis screening in patients with autoimmune diseases: a systematic review and meta-analysis

ObjectiveInterferon γ release assay (IGRA) is commonly used to diagnose latent TB infection (LTBI). Immunosuppressive therapy may affect its performance but data are conflicting. We aimed to determine the effect...

Estimation of the prevalence of latent tuberculosis infection in patients with moderate to severe plaque psoriasis in Spain: The Latent study

Background and objectiveAnti-tumor necrosis factor therapy for moderate to severe psoriasis can increase the risk of active tuberculosis in patients who have latent tuberculosis infection (LTBI). The main objective of this study was to estimate the prevalence of LTBI in patients with moderate to severe plaque psoriasis being treated in dermatology clinics in Spain. Material and methodNon-interventional, cross-sectional, national epidemiological study conducted in Spain in 2011-2012. Patients with moderate to severe plaque psoriasis were included if they had undergone at least one tuberculin skin test (TST) and/or been evaluated with an interferon-γ release assay (IGRA) based on enzyme-linked immunosorbent assay (QuantiFERON TB Gold In-Tube) in the 2 years preceding the study. ResultsData for 440 patients were valid for analysis. In total, 97.7% of the patients had undergone a TST, with a positive result in 23%. Of the 238 patients in whom the initial result was negative, 5% converted to positive on re-testing for a booster effect. IGRA results were available for 16.8%, 20.5% of them positive. Two of the patients with positive IGRA results had a negative TST. The prevalence of LTBI in the whole sample was 26.6%. The degree of concordance between the TST and the IGRA was moderate (κ=0.516; P<.001). ConclusionsThe prevalence of LTBI in this study was similar to previous estimates for Spain.

No added value of interferon-γ release to a prediction model for childhood tuberculosis.

The predictive value of a combination of clinical and radiological features with interferon-γ release assay (IGRA) for diagnosis of active tuberculosis (TB) disease among TB-exposed children is unknown.150 symptomatic HIV-negative children (aged 3 months to 14 years), prospectively recruited through active contact tracing, were included. Backward stepwise logistic regression and bootstrapping techniques were used for the development and internal validation of a clinical prediction model for active TB disease. Model discrimination and incremental value of a positive IGRA test were assessed by area under the receiver operating characteristic curve (AUC).35 (23%) children were diagnosed with active TB disease and started on treatment and 115 (77%) had other respiratory tract infections. A final parsimonious clinical model, comprising age <5 years (adjusted (a)OR 4.8, 95% CI 2.0-11.5) and lymphadenopathy on clinical examination (aOR 4.9, 95% CI 1.8-13.0) discriminated active TB disease from other disease with an AUC of 0.70 (95% CI 0.61-0.80). A positive IGRA result did not improve the discriminatory ability of the clinical model (c-statistic 0.72 versus 0.70; p=0.644).A clinical algorithm, including age <5 years and lymphadenopathy classified 70% of active TB disease among symptomatic TB-exposed children. IGRA does not add any discriminatory value to this prediction model.