Contribution of Interferon gamma release assays testing to the diagnosis of latent tuberculosis infection in HIV-infected patients: A comparison of QuantiFERON-TB gold in tube, T-SPOT.TB and tuberculin skin test

ABSTRACT: BACKGROUND: Diagnosis and treatment of latent tuberculosis infection (LTBI) is the most effective strategy to control tuberculosis (TB) among patients with HIV infection. The tuberculin skin test (TST) was the only available method to identify LTBI. The aim of the present work was to evaluate the usefulness of the interferon-gamma release assays (IGRAs): QuantiFERONtuberculosis (TB) Gold-In-Tube test (QFG) and T-SPOT.TB for the diagnosis of LTBI in a diverse cohort of HIV-infected patients. METHODS: A prospective study was carried out in consecutive patients cared for in a single institution in Spain from January 2009 to October 2010. IGRAS and tuberculin skin test (TST) were performed simultaneously. TST induration [greater than or equal to] 5 mm was considered positive. RESULTS: QFG, T-SPOT.TB and TST were performed in 373 subjects. Median CD4 cell count was 470/mul with a median nadir of 150/mul. TST, QFG and T-SPOT.TB were positive in 13.3%, 7.5% and 18.5% cases respectively. Among 277 patients with neither past or current TB nor previous treatment for LTBI and who had TST results, a positive TST result was obtained in 20 (7.2%) cases. When adding QFG results to TST, there were a total of 26 (8.6%) diagnoses of LTBI. When the results of both IGRAs were added, the number of diagnoses increased to 54 (17.9%) (incremental difference: 10.7% [95% confidence interval [CI]:5.3-16.2%] [p <0.001]), and when both IGRAs were added, the number of diagnoses reached 56 (18.5%) (incremental difference: 11.3% [95% CI:5.7%-16.9%] [p < 0.001]). Patients with a CD4 cell count greater than 500 cells/mul and prior stay in prison were more likely to have a diagnosis of LTBI by TST and/or QFG and/or T-SPOT.TB (adjusted odds ratio [aOR]: 3.76; 95% CI, 1.4 - 9.89; and aOR: 3.3; 95% CI, 1.3 - 8.3, respectively). CONCLUSIONS: IGRAs were more sensitive than TST for diagnosis of M. tuberculosis infection in HIVinfected patients. Dual sequential testing with TST and IGRAs may be the optimal approach for LTBI screening in this population.     

Results of a tuberculosis-specific IFN-gamma assay in children at high risk for tuberculosis infection.

The specificity of the tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection (LTBI) is adversely affected by bacille Calmette-Guérin (BCG) vaccination and infection with non-tuberculous mycobacteria. Interferon-gamma release assays (IGRAs) using TB-specific antigens promise higher specificity. We compared a new IGRA and TST in 184 schoolchildren at high risk for LTBI. The IGRA and TST were positive in 33.2% and 43.5% of the children, respectively (P < 0.001). If studies confirm that this difference is due to higher specificity of this IGRA, it may have an important role to play in the diagnosis of LTBI and identification of children at true risk for TB.     

Is the T-cell-based interferon-gamma releasing assay feasible for diagnosis of latent tuberculosis infection in an intermediate tuberculosis-burden country?

The diagnosis of active and latent tuberculosis infection (LTBI) remains a challenge, especially in light of the fact that the tuberculin skin test (TST), which has been used to diagnose LTBI for over a century, has many well-known drawbacks. This study aimed to compare the diagnostic performance of the T-cell-based interferon-gamma releasing assay (IGRA) T-SPOT.TB with the TST for the diagnosis of LTBI in an intermediate tuberculosis (TB)-burden country with high BCG coverage. For this purpose, a total of 91 participants, including culture-confirmed TB patients, healthy contacts known to have been exposed to Mycobacterium tuberculosis, and healthy volunteers, selected from a BCG-vaccinated population were recruited. The sensitivities of the T-SPOT.TB and TST were 79.3 and 25.8%, and the specificities were 75.9 and 56.7%, respectively. The negative- and positive-predictive values for T-SPOT.TB and TST were 78.6 and 76.7% and 42.5 and 38.1%, respectively. The diagnostic performance of the TST in LTBI diagnosis is therefore severely diminished in BCG-vaccinated populations, with the sensitivity and specificity of the T-SPOT.TB assay being markedly higher. IGRAs have been reported to have higher diagnostic sensitivity and specificity in low TB-incidence settings than those seen here. Further larger scale studies in high and intermediate TB-incidence settings are therefore warranted.     

Screening of latent tuberculosis infection by interferon-γ release assays in rheumatic patients: a systemic review and meta-analysis

The aim of this study is to assess the diagnostic value of interferon-γ release assays (IGRAs) for latent tuberculosis infection (LTBI) in patients with rheumatic disease before receiving biologic agents. MEDLINE and EMBASE databases were used for searching studies concerning the evaluation on the performance of IGRAs [QuantiFERON-TB Gold (QFT-G), QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB] in rheumatic patients before biological therapy. After assessing the quality of all studies included in the review, we summarized the results in subgroups using forest plots and calculated pooled estimates if applicable. The search identified 11 studies with a total sample size of 1940 individuals. Compared with the tuberculin skin test (TST), the pooled agreements in QFT-G/GIT and T-SPOT.TB were 72 % (95 % confidence interval (CI) 65, 78 %) and 75 % (95 % CI 67, 83 %), respectively. BCG vaccination was positively correlated with positive rates of TST (pooled odds ratio (OR) 1.64, 95 % CI 1.06, 2.53). Compared with TST, IGRAs were better associated with the presentence of one or more tuberculosis (TB) risk factors. Neither steroid nor disease-modifying anti-rheumatic drugs (DMARDs) significantly affect positive IGRA results. In contrast, TST positivity was significantly impacted by the use of steroid (pooled OR 0.45, 95 % CI 0.30, 0.69), but less significantly by the use of DMARDs (pooled OR 0.78, 95 % CI 0.50, 1.21). In conclusion, in rheumatic patients with previous BCG vaccination or currently on steroid therapy, IGRAs would be the better choice to identify LTBI by decreasing the false-positivity and false-negativity rate compared with conventional TST.     

风湿性疾病的T细胞γ干扰素释放分析诊断潜伏性结核分枝杆菌感染

风湿性疾病患者的机体处于免疫抑制状态,而其中接受肿瘤坏死因子α(tumor necrosis factor α,TNF-α)拮抗剂治疗的患者更可能存在结核(tuberculosis,TB)复燃的风险.T细胞γ干扰素释放试验(interferon-γ release assays,IGRA)对于潜伏性结核感染(laten...     

Tuberculosis infection in drug users: interferon-gamma release assay performance.

SETTING: An inner city neighborhood in Houston, Texas, known for a high rate of drug use. OBJECTIVE: To determine the prevalence of latent tuberculosis infection (LTBI) using the QuantiFERON-TB Gold (QFT-G) test, the TSPOT.TB test and the tuberculin skin test (TST) in drug users and to evaluate the performance of the QFT-G and TSPOT.TB tests vs. the TST. DESIGN: Cross-sectional study. Bivariate and multivariate logistic regression analyses were used to determine risks associated with each test outcome. RESULTS: The prevalence of LTBI in 119 drug users studied was 28% by TST and 34% by QFT-G and T-SPOT.TB. Kappa statistics indicated fair to moderate concordance between QFT-G and TSPOT.TB vs. TST. About one-fifth of the population that tested negative with TST was positive with either QFT-G or T-SPOT.TB. On multivariate analysis, the likelihood of testing QFT-positive or T-SPOT.TB-positive increased by 8% and 6%, respectively, for every year of age; TST positivity was associated with smoking crack at home; being Caucasian or having a history of alcohol use was positively associated with a positive T-SPOT.TB test. CONCLUSION: Interferon-gamma release assays (IGRAs) are superior to the TST in drug users with a higher prevalence of LTBI. Future studies need to assess the predictive value of IGRAs on the progression from LTBI to active TB in high-risk populations.     

Comparison of IGRA and TST in the diagnosis of latent tuberculosis among women of reproductive age in South India

BackgroundLatent tuberculosis infection (LTBI) is a mycobacterial infection defined on the basis of cellular immune response to mycobacterial antigens. The tuberculin skin test (TST) and the Interferon-Gamma Release Assay (IGRA) are the two tests currently used to establish the diagnosis of LTB. Literature suggests that a study regarding tuberculosis (TB) infection among women of reproductive age group is limited.MethodsFemale household contact, married, aged 18–49 years underwent written consent form and are screened for LTBI using the TST and IGRA. Participants are injected with TST [5 tuberculin unit (TU), purified protein derivative (PPD)] and IGRA [QuantiFERON®-TB Gold Plus kit (QFT-Plus)]. All the household contacts were followed-up for one year for incident TB cases. Statistical analysis was done using STATA version 14 (StataCorp., Texas, USA). Cohen's kappa test was used to determine the agreement between two tests.ResultsThe prevalence of LTBI was found to be 69% (either TST or IGRA positive). Positivity rate of IGRA was higher when compared to that of TST. Out of 139 participants, 68 (49%) tested positive for TST, 80 (57.6%) tested positive for IGRA and 52 (37.4%) tested positive for both. Discordant results were observed in about two fifth of the study population and there was poor agreement between the two tests.ConclusionLongitudinal studies are required to detect incident TB cases to evaluate the usefulness of these tests. The study was found that IGRA is more consistent to diagnosis of latent tuberculosis infection than the TST. Such studies can also be performed in varied settings among different populations which would help us to improve the diagnosis of LTBI and consequently help in TB control.     

A comparison of an interferon-gamma release assay and tuberculin skin test in refractory inflammatory disease patients screened for latent tuberculosis prior to the initiation of a first tumor necrosis factor α inhibitor

Treatment with TNFα inhibitors increases risk of reactivating a latent tuberculosis\infection (LTBI). Therefore screening, prior to therapy with TNFα inhibitors, has been recommended, even in low-endemic areas such as well-developed Western Europe countries. We evaluated interferon-gamma release assay (IGRA), as opposed to tuberculin skin test (TST), for detection of LTBI in refractory inflammatory disease patients prior to the initiation of a first TNFα inhibitor. In addition, we evaluated the impact of impaired cellular immunity on IGRA. Patients starting on TNFα inhibition were screened for LTBI by TST and IGRA (Quantiferon-TB Gold). Data on tuberculosis exposure and Bacillus Calmette–Guérin (BCG) vaccination were obtained. Cellular immunity was assessed by CD4⁺ T lymphocyte cell count. Nine out of 56 patients (16.1%) tested positive for LTBI. A concordant positive result was present in three patients with a medical history of tuberculosis exposure. Six patients with discordant test results had either: (1) a negative TST and positive IGRA in combination with a medical history of tuberculosis exposure (n = 1) or (2) a positive TST and negative IGRA in combination with BCG vaccination (n = 3) or a medical history of tuberculosis exposure (n = 2). CD4⁺ T lymphocyte cell counts were within normal limits, and no indeterminate results of IGRA were present. IGRA appears reliable for confirming TST and excluding a false positive TST (due to prior BCG vaccination) in this Dutch serie of patients. In addition, IGRA may detect one additional case of LTBI out of 56 patients that would otherwise be missed using solely TST. Immune suppression appears not to result significantly in lower CD4⁺ T lymphocyte cell counts and indeterminate results of IGRA, despite systemic corticosteroid treatment in half of the patients. Confirmation in larger studies, including assessment of cost-effectiveness, is required.     

Interferon-gamma release assays and TB screening in high-income countries: a cost-effectiveness analysis.

OBJECTIVE: Interferon-gamma release assays (IGRA) are now available alternatives to tuberculin skin testing (TST) for detection of latent tuberculosis infection (LTBI). We compared the cost-effectiveness of TST and IGRA in different populations and clinical situations, and with variation of a number of parameters. METHODS: Markov modelling was used to compare expected TB cases and costs over 20 years following screening for TB with different strategies among hypothetical cohorts of foreign-born entrants to Canada, or contacts of TB cases. The less expensive commercial IGRA, Quanti-FERON-TB Gold (QFT), was examined. Model inputs were derived from published literature. RESULTS: For entering immigrants, screening with chest radiograph (CXR) would be the most and QFT the least cost-effective. Sequential screening with TST then QFT was more cost-effective than QFT alone in all scenarios, and more cost-effective than TST alone in selected subgroups. Among close and casual contacts, screening with TST or QFT would be cost saving; savings with TST would be greater than with QFT, except in contacts who were bacille Calmette-Guérin (BCG) vaccinated after infancy. CONCLUSIONS: Screening for LTBI, with TST or QFT, is cost-effective only if the risk of disease is high. The most cost-effective use of QFT is to test TST-positive persons.     

Snapshot of Quantiferon TB gold testing in Northern Mexico

Most people infected with Mycobacterium tuberculosis have an asymptomatic condition named latent tuberculosis. These people do not have bacilli in the corporal secretions and are hard to diagnose by conventional laboratory tests. Diagnosis of latent tuberculosis infection (LTBI) in México is based on the tuberculin skin test (TST). This test has disadvantages, principally because the vaccine containing the Bacille Calmette-Guérin (BCG) is applied to 99% of this population and causes false positive TST outcomes. Recently, interferon-gamma release assays (IGRA) have been demonstrated to be a good test to detect latent tuberculosis with equal or better sensitivity to TST and without interference from BCG. However, in México the IGRA are an uncommon test due to the higher cost compared to TST. The main objective of this work was demonstrate the potential utility of the Quantiferon TB(?) gold in tube (QTB(?)-GIT) test to detect latent TB in a population from northern México. Samples from 106 subjects with close contact, or without contact, with actively infected TB patients were tested to detect LTBI. Our results show a significant difference between individuals in close contact with active TB patients (39.7%) compared to those without contact (3.2%), p < 0.01. The concordance between TST and QTB(?)-GIT was poor (κ = 0.31). Our preliminary results show that the QTB(?)-GIT has better capacity than TST to detect latent tuberculosis infection.     

Empfehlungen für das Tuberkulose-Screening vor Gabe von TNF-α-Inhibitoren bei rheumatischen Erkrankungen

Due to the increased risk of tuberculosis (TB) under treatment with TNF-α inhibitors for rheumatoid arthritis and other autoimmune diseases, precautionary measures are required before initiating TNF-α-inhibitor therapy. Patients should have active TB ruled out and screening for latent TB infection should be performed. The screening should include chest X-ray, complete medical history, and the administration of a highly specific interferon-γ-release assay (IGRA). (In the future, the reimbursement of IGRA tests under an analogue procedure code is expected to be formalized by the application of a code specific to the TB-IGRA procedure.) As tuberculin skin test (TST) results can be expected to be either false-positive or false-negative in these patients, the TST, as commonly performed in the past, is recommended only in exceptional situations. For chemopreventive treatment of latent TB infection (LTBI), isoniazid is usually given for 9 months.     

Yield and cost effectiveness of mycobacterial infection detection using a simple IGRA-based protocol in UK subjects with inflammatory bowel disease suitable for anti-TNFα therapy

Background and aimsTesting for LTBI is recommended prior to anti-TNFα agents. This includes an assessment of TB risk factors, chest radiograph, and interferon-gamma release assay alone or with concurrent Tuberculin skin testing. Here we review our experience and cost-effectiveness of using T-SPOT.TB IGRA to detect mycobacterial infection in patients with IBD suitable for anti-TNFα therapy.MethodsThis was a single-centre, retrospective review and economic evaluation (compared to British Thoracic Society guidance) of 125 adult IBD patients (90 anti-TNFα naïve, 35 established on anti-TNFα) tested for LTBI using T-SPOT.TB IGRA.ResultsAll subjects had normal chest radiographs and no clinical evidence for TB. 109 (87%) were BCG vaccinated. 27 (22%) of all patients tested were not using immunomodulation at the time of testing. 66 (53%) were taking thiopurines, 22 (18%)corticosteroids, and 35 (28%) anti-TNFα agents. One hundred twenty two (98%) had a negative IGRA result, two (2%) had positive results, and one (1%) had an indeterminate IGRA. A strategy using IGRA to guide TB preventative treatment produced cost savings of £10.79 per person compared to the BTS guidance. Eighty eight percent of the anti-TNFα naïve group have subsequently received treatment with either infliximab or adalimumab (median follow-up of 24 months, IQR 18–30) with no cases of TB disease occurring.ConclusionsThe use of a simple screening protocol for LTBI incorporating T-SPOT.TB IGRA in place of TST in a largely BCG vaccinated population, many using immunomodulatory agents, appears to work well and is a cost-effective strategy in our IBD service.     

High level of discordant IGRA results in HIV-infected adults and children.

SETTING: Tygerberg district, Western Cape Province, South Africa. OBJECTIVE: To measure the agreement of two interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST) for the detection of Mycobacterium tuberculosis infection in human immunodeficiency virus (HIV) infected adults and children in a setting highly endemic for tuberculosis (TB). DESIGN: Cross-sectional study. RESULTS: In HIV-infected adults (n=20) and children (n=23), tests yielded discordant results, with 61% of individuals testing positive with T-SPOT.TB, 41% with TST and 28% with QuantiFERON TB Gold (QTF). In children, there was poor agreement between the TST and T-SPOT.TB (kappa [kappa]=-0.02), but moderate agreement between the TST and QTF (kappa=0.44). In adults, there was moderate agreement between the TST and T-SPOT.TB (kappa=0.43), and the TST and QTF (kappa = 0.46). In children and adults, there was fair agreement between the T-SPOT.TB and QTF (kappa=0.33). Twenty per cent of adults had >or=1 indeterminate IGRA results. CONCLUSIONS: There is poor to moderate agreement between the TST and IGRAs in HIV-infected adults and children. T-SPOT.TB may have improved sensitivity for detection of M. tuberculosis infection in HIV-infected individuals compared to the QTF and the TST. In HIV-infected individuals, IGRA test properties are affected by test cut-off point and nil control responses.     

Challenges in diagnosing latent tuberculosis infection in patients treated with tumor necrosis factor antagonists

Reactivation of latent tuberculosis infection (LTBI) is well recognized as an adverse event associated with anti-tumor necrosis factor-α (anti-TNF-α) therapy. The strengths and weaknesses of current techniques for detecting LTBI in patients with chronic inflammatory diseases such as rheumatoid arthritis (RA) and psoriasis have not been fully examined. T cell hyporesponsiveness due to immunosuppression caused by illness or drugs, referred to as anergy, may produce false-negative tuberculin skin test (TST) and interferon-γ release assay (IGRA) results. The literature suggests that anergy may influence screening performance of TST and IGRA tests in candidates for anti-TNF-α therapy. Conversely, the potential for false-positive TST and IGRA results must be considered, as treatment for LTBI may be associated with significant morbidity. This review examines the reliability issues related to LTBI diagnostic testing and provides practical direction to help prevent LTBI reactivation and facilitate successful anti-TNF-α treatment.     

Influence of previous tuberculin skin test on serial IFN-γ release assays

Tuberculin skin test (TST) and interferon-γ release assays (IGRAs) have been proposed for serial testing in tuberculosis. In the present study, we assessed the effect of TST on subsequent QuantiFERON-TB Gold In-Tube (QFT-GIT) results by monitoring the evolution of responses during a follow-up period of 6 weeks. One hundred and two subjects were initially tested with QFT-GIT and subsequently with TST; then the QFT-GIT was performed serially 1, 2, 4, and 6 weeks after the TST. A subgroup of 40 subjects was also assessed by older version of the QuantiFERON-TB Gold (QFT-G) assay. The results showed no significant variation in IFN-γ response over time in the tested patients, although two TST-positive subjects showed evidence of possible boosting effect. In addition, a direct comparison between the QFT-G and QFT-GIT test showed no significant differences at any time point with excellent agreement between two tests. No significant differences were seen in IFN-γ responses between BCG-unvaccinated and BCG-vaccinated patients at each time point. In conclusion, our findings indicate that TST does not influence the outcome of subsequent IGRAs testing in individuals with negative TST results, but it can boost the IFN-γ response in subjects sensitized to TB antigens and not detected by IGRA.     

Comparison of an interferon-gamma assay with tuberculin skin testing for detection of tuberculosis (TB) infection in patients with rheumatoid arthritis in a TB-endemic population

OBJECTIVE: Tuberculosis (TB) in patients with rheumatoid arthritis (RA) undergoing treatment with anti-tumor necrosis factor (TNF) agents is commonly the result of reactivation of latent TB infection (LTBI); detection and treatment of LTBI is essential before treatment with anti-TNF agents. We reported previously that the tuberculin skin test (TST) is inaccurate for diagnosis of LTBI in patients with RA. Here, we compare the prevalence of LTBI in RA patients and matched controls according to positive TST and QuantiFeron-TB Gold In-Tube version (QFT) results and determine their agreement. METHODS: A cross-sectional study of 101 RA patients and 93 controls was conducted in Lima, Perú, where the prevalence of LTBI in the general population has been estimated to be 68%. Blood was drawn for QFT assay followed by TST using 2-TU of RT 23 purified protein derivative. TST was deemed positive at >or= 5 mm for RA patients and >or= 10 mm for controls. RESULTS: There were no significant differences between RA patients and controls for age, sex, bacillus Calmette-Guérin vaccination, or history of or contact with TB. 88% of patients had active RA disease and 2 (1.9%) patients had indeterminate QFT results. The number of subjects testing positive with the QuantiFeron assay was comparable between patients and controls (44.6% vs 59.1%, respectively), whereas the TST detected significantly less LTBI among RA patients (26.7%) than controls (65.6%). Thus, the rate of LTBI in RA patients represented 75% and 41% of the rate in their controls using QFT or TST, respectively (p = 0.008). Poor agreement between TST and QFT was seen in RA patients, but in controls, good agreement was observed between these tests. CONCLUSION: In a TB-endemic population, the QuantiFeron-TB Gold In-Tube assay seemed to be a more accurate test for detection of LTBI in RA patients compared with the TST, and may potentially improve the targeting of prophylactic therapy before treatment with anti-TNF agents.     

Cost-effectiveness of including tuberculin skin testing in an IPT program for HIV-infected persons in Uganda.

SETTING: Tuberculosis (TB) is the most common opportunistic infection among persons with human immunodeficiency virus or the acquired immune-deficiency syndrome (HIV/AIDS). Isoniazid preventive therapy (IPT) effectively treats latent TB infection (LTBI) and prevents progression to active TB. OBJECTIVE: To analyse the costs and cost-effectiveness of tuberculin skin testing (TST) prior to offering IPT. DESIGN: We implemented a program for LTBI screening and IPT using TST for persons with HIV at a voluntary counseling and testing (VCT) center in Kampala, Uganda. Cost-effectiveness analyses using Markov methods were adopted to compare strategies of using and not using TST before offering IPT. RESULTS: The program enrolled 7073 persons with HIV. Based on the prevalence of LTBI in the population, 34/100 HIV-infected patients would benefit from IPT. The results showed that 28% of LTBI patients would be treated using the TST strategy, and 40% would be treated with a non-TST strategy. Compared to no intervention, the estimated incremental cost of identifying and providing IPT using TST was dollars 211 per patient; the incremental cost using a non-TST strategy was dollars 768 per patient. CONCLUSION: At a large VCT center in Uganda, the inclusion of TST to identify the HIV-infected persons who will most benefit from IPT is cost-effective.     

Screening for latent tuberculosis infection prior to biologic therapy in patients with chronic immune-mediated inflammatory diseases (IMID): Interferon-gamma release assay (IGRA) versus tuberculin skin test (TST)

BackgroundThe screening for latent tuberculosis infection (LTBI) is mandatory before initiating biologics in patients with chronic immune-mediated inflammatory disease (IMID). The recommendations are based on the tuberculin skin test (TST) and interferon-gamma release assay (IGRA).Aim of the workTo evaluate the agreement between the two tests in the diagnosis of LTBI and to identify risk factors associated with positive TST and IGRA results.Patients and methodsMedical records of 105 IMID patients going to receive a biologic agents were extracted in a cross sectional study (2015–2017). No biologics was undertaken before LTBI screening. All patients underwent IGRA and chest radiography. TST was performed in 94 cases.ResultsThe mean age of the patients was 47.7 ± 14.4 years and disease duration of 11.2 ± 7.6 years. Agreement between the 2 tests results was low (κ coefficient = 0.08). The sensitivity of TST and IGRA was equally low but the specificity of IGRA was higher. Replacing TST results by positive IGRA showed that number of patients who would take anti-tuberculous chemoprophylaxis will be significantly reduced by 46.5% (from 40.9% to 21.9%; p = 0.0002). TST results were significantly less positive for patients receiving immunosuppressives than for those receiving no treatment (35.1% vs 42.5%, p = 0.031). IGRA results were associated with absence of Bacilli Calemtte-Guérin vaccination. Age was the only risk factor for LTBI associated with both IGRA and TST positivity (p = 0.031, p = 0.011 respectively).ConclusionsTST and IGRA have a low agreement. Both tests should be included in the strategy to diagnose LTBI prior to biologic therapy in IMID patients.     

Contribution of a IFN-gamma assay in contact tracing for tuberculosis in a low-incidence, high immigration area

AIMS OF STUDY: to analyse, in contacts exposed to smear+/culture + (S+/C+) or S-/C+ TB, most of whom are foreign-born: 1) correlation between T-SPOT.TB IFN-gamma release assay (Oxford Immunotec, UK), TST and exposure scores; 2) agreement between T-SPOT.TB and TST in Bacillus of Calmette-Guérin (BCG) vaccinated and non-vaccinated subjects, and 3) impact of results of T-SPOT.TB on diagnosis and treatment for latent tuberculosis infection (LTBI). PATIENTS AND METHODS: TST and T-SPOT.TB were performed in 295 contacts (74% foreign-born) 8-12 weeks after exposure. Contacts completed five exposure scores. Data were analysed according to most recent US (ATS/CDC), British (NICE) and Swiss guidelines. RESULTS: T-SPOT.TB was positive in 115 (39%) and indeterminate in 15 subjects (5.1%). Neither TST, nor T-SPOT.TB was significantly related to exposure scores or infectiousness of the index case. In multivariate analysis, incidence of TB in country of origin was the strongest predictor of result of TST or T-SPOT.TB. Agreement between TST and T-SPOT.TB (kappa: 0.19-0.27) was low but improved in non BCG-vaccinated subjects (kappa: 0.28-0.47). According to guidelines referred to, 10-24% of subjects screened were T-SPOT.TB+/TST-: the prognosis of this group is yet undetermined. Another 10-27% were T-SPOT.TB-/TST+: present guidelines recommend withholding treatment for LTBI in these subjects although longitudinal data are still scarce. CONCLUSIONS: The lack of a relationship between T-SPOT.TB and exposure scores probably results from both the variability inherent to the design of this study (ie, multiple contact investigations, exposure in different settings) and limits in the performance of the IGRA tested. Longitudinal data are needed to clarify the risk of TB in T-SPOT.TB+/TST- individuals. Unreliability of diagnosis of LTBI in spite of the present use of IGRA in algorithms is illustrated by the wide variations in identification of LTBI according to different guidelines referred to.     

Tuberculosis screening among HIV-infected patients: tuberculin skin test vs. interferon-gamma release assay

National guidelines recommend screening for latent tuberculosis infection (LTBI) in all HIV-infected patients. Thus, the objective of this study was to measure protocol adherence to national guidelines regarding LTBI screening for HIV-infected patients entering care at an urban primary care clinic specializing in HIV care, identify clinical and other characteristics associated with adherence, and determine whether transitioning from the tuberculin skin test (TST) to the interferon-gamma release assay (IGRA) improved adherence. We conducted a retrospective study using protocol adherence to LTBI screening guidelines within twelve months of entering care at an HIV clinic as the primary outcome. Successful protocol adherence was defined as the placement and reading of a TST, performance of an IGRA, or a note in study clinic records documenting prior testing or treatment for tuberculosis in an outside setting. Multivariable modified Poisson regression models were used in analyses. Overall, 32% (n?=?118/372) of patients received LTBI screening within twelve months of entering care. Protocol adherence to LTBI screening guidelines increased from 28% to 37% following the transition from TST to IGRA screening. IGRA screening [adjusted prevalence ratio: 1.45, 95% confidence limits: (1.07, 1.96)], male sex [1.47 (1.05, 2.07)], transfer patient status [1.51 (1.05, 2.18)], and greater than one year of clinic attendance [1.62 (1.06, 2.48)] were independently associated with protocol adherence. Among patients without prior LTBI screening or treatment, patients entering the clinic in 2013 under the IGRA screening protocol were more likely to be screened for LTBI compared to patients entering under the TST screening protocol (34.3% vs. 9.7%, p?相似文献