Positive QuantiFERON-TB Gold In-Tube Research Articles

Serial interferon-gamma release assays during treatment of active tuberculosis in young adults

BackgroundThe role of interferon-γ release assay (IGRA) in monitoring responses to anti-tuberculosis (TB) treatment is not clear. We evaluated the results of the QuantiFERON-TB Gold In-tube (QFT-GIT) assay over time during the anti-TB treatment of adults with no underlying disease.MethodsWe enrolled soldiers who were newly diagnosed with active TB and admitted to the central referral military hospital in South Korea between May 1, 2008 and September 30, 2009. For each participant, we preformed QFT-GIT assay before treatment (baseline) and at 1, 3, and 6 months after initiating anti-TB medication.ResultsOf 67 eligible patients, 59 (88.1%) completed the study protocol. All participants were males who were human immunodeficiency virus (HIV)-negative and had no chronic diseases. Their median age was 21 years (range, 20-48). Initially, 57 (96.6%) patients had positive QFT-GIT results, and 53 (89.8%), 42 (71.2%), and 39 (66.1%) had positive QFT-GIT results at 1, 3, and 6 months, respectively. The IFN-γ level at baseline was 5.31 ± 5.34 IU/ml, and the levels at 1, 3, and 6 months were 3.95 ± 4.30, 1.82 ± 2.14, and 1.50 ± 2.12 IU/ml, respectively. All patients had clinical and radiologic improvements after treatment and were cured. A lower IFN-γ level, C-reactive protein ≥ 3 mg/dl, and the presence of fever (≥ 38.3°C) at diagnosis were associated with negative reversion of the QFT-GIT assay.ConclusionAlthough the IFN-γ level measured by QFT-GIT assay decreased after successful anti-TB treatment in most participants, less than half of them exhibited QFT-GIT reversion. Thus, the reversion to negativity of the QFT-GIT assay may not be a good surrogate for treatment response in otherwise healthy young patients with TB.

Analysis of the utility of QuantiFERON‐TB GoldTM in tube and measurement of IFNγ release by peripheral mononuclear cells in response to different mycobacterium antigen in the work‐up of patients with uveitis

Abstract Purpose Tuberculosis remains an important cause of infectious uveitis and immune reaction against mycobacteria may contribute to the development of certain forms of autoimmune uveitis. Moreover, many non‐infectious uveitis patients are treated with immunomodulatory treatment. The evaluation of tuberculosis immunity is thus an important aspect in the work‐up of patients with uveitis. In this work, we would like to investigate the usefulness of different methods of tuberculosis immunity testing in a series of patients with intraocular inflammation. Methods Patients with uveitis will undergo a standard diagnosis procedure, including a chest Xray. Quantiferon TB Gold in Tube (QFT) and tuberculin skin test (TST) will be performed. IFNγ production by mononuclear cells in response to PPD and to HBHA will be measured by ELISA. Results Thirty‐two patients have already been recruited. Sixteen had a negative QFT and a negative TST. In two of them, mononuclear cells produce IFNγ in response to PPD (but not to HBHA) and in 1 in response to HBHA (but not to PPD). In 11 patients QFT and TST were positive. In this group, IFNγ response to PPD was observed in 82% but only in 50% in response to HBHA. Discordant results between QFT and TST were observed in 5 patients. One had a positive QFT and a negative TST and 4 had a positive TST and a negative QFT. In this group IFNγ response to PPD or HBHA was not observed. Conclusion Discordant results between QuantiFERON‐TB Gold and TST were observed in 15 % of uveitis patients. Analysis of the IFNγ production in response to PPD and to HBHA seems to add important information in both concordant and discordant group.

Predictors of persistently positive Mycobacterium-tuberculosis-specific interferon-gamma responses in the serial testing of health care workers

BackgroundData on the performance of Mycobacterium-tuberculosis-specific interferon-(IFN)-γ release assays (IGRAs) in the serial testing of health care workers (HCWs) is limited. The objective of the present study was to determine the frequency of IGRA conversions and reversions and to identify predictors of persistent IGRA positivity among serially tested German HCWs in the absence of recent extensive tuberculosis (TB) exposure.MethodsIn this observational cohort-study HCWs were prospectively recruited within occupational safety and health measures and underwent a tuberculin skin test (TST) and the IGRA QuantiFERON®-TB Gold In-Tube (QFT-GIT) at baseline. The QFT-GIT was repeated 18 weeks later in the median. QFT-GIT conversions (and reversions) were defined as baseline IFN-γ < 0.35 IU/ml and follow-up IFN-γ ≥ 0.35 IU/ml (and vice versa). Predictors of persistently positive QFT-GIT results were calculated by logistic regression analysis.ResultsIn total, 18 (9.9%) and 15 (8.2%) of 182 analyzed HCWs were QFT-GIT-positive at baseline and at follow-up, respectively. We observed a strong overall agreement between baseline and follow-up QFT-GIT results (κ = 0.70). Reversions (6/18, 33.3%) occurred more frequently than conversions (3/162, 1.9%). Age and positive prior and recent TST results independently predicted persistent QFT-GIT positivity. Furthermore, the chance of having persistently positive QFT-GIT results raised about 3% with each additional 0.1 IU/ml increase in the baseline IFN-γ response (adjusted odds ratio 1.03, 95% confidence interval 1.01-1.04). No active TB cases were detected within an observational period of more than two years.ConclusionsThe QFT-GIT's utility for the application in serial testing was limited by a substantial proportion of reversions. This shortcoming could be overcome by the implementation of a borderline zone for the interpretation of QFT-GIT results. However, further studies are needed to clearly define the within-subject variability of the QFT-GIT and to confirm that increasing age, concordantly positive TST results, and the extend of baseline IFN-γ responses may predict the persistence of QFT-GIT positivity over time in serially tested HCWs with only a low or medium TB screening risk in a TB low-incidence setting.

Diagnosis and follow-up of treatment of latent tuberculosis; the utility of the QuantiFERON-TB Gold In-tube assay in outpatients from a tuberculosis low-endemic country

BackgroundInterferon-gamma (IFN-γ) Release Assays (IGRA) are more specific than the tuberculosis skin test (TST) in the diagnosis of latent tuberculosis (TB) infection (LTBI). We present the performance of the QuantiFERON®-TB Gold In-tube (QFT-TB) assay as diagnostic test and during follow-up of preventive TB therapy in outpatients from a TB low-endemic country.Methods481 persons with suspected TB infection were tested with QFT-TB. Thoracic X-ray and sputum samples were performed and a questionnaire concerning risk factors for TB was filled. Three months of isoniazid and rifampicin were given to patients with LTBI and QFT-TB tests were performed after three and 15 months.ResultsThe QFT-TB test was positive in 30.8% (148/481) of the total, in 66.9% (111/166) of persons with origin from a TB endemic country, in 71.4% (20/28) previously treated for TB and in 100% (15/15) of those diagnosed with active TB with no inconclusive results. The QFT-TB test was more frequently positive in those with TST ≥ 15 mm (47.5%) compared to TST 11-14 mm (21.3%) and TST 6-10 mm (10.5%), (p < 0.001). Origin from a TB endemic country (OR 6.82, 95% CI 1.73-26.82), recent stay in a TB endemic country (OR 1.32, 95% CI 1.09-1.59), duration of TB exposure (OR 1.59, 95% CI 1.14-2.22) and previous TB disease (OR 11.60, 95% CI 2.02-66.73) were all independently associated with a positive QFT-TB test. After preventive therapy, 35/40 (87.5%) and 22/26 (84.6%) were still QFT-TB positive after three and 15 months, respectively. IFN-γ responses were comparable at start (mean 6.13 IU/ml ± SD 3.99) and after three months (mean 5.65 IU/ml ± SD 3.66) and 15 months (mean 5.65 IU/ml ± SD 4.14), (p > 0.05).ConclusionOnly one third of those with suspected TB infection had a positive QFT-TB test. Recent immigration from TB endemic countries and long duration of exposure are risk factors for a positive QFT-TB test and these groups should be targeted through screening. Since most patients remained QFT-TB positive after therapy, the test should not be used to monitor the effect of preventive therapy. Prospective studies are needed in order to determine the usefulness of IGRA tests during therapy.

Interferon-γ Release Assay among Tuberculin Skin Test Positive Students in Korean High Schools

Background: There are several active tuberculosis (TB) cases in Korean high schools each school year. The risk of transmission in schools is extremely high due to the considerable time spent in closed classrooms. We evaluated the control of latent tuberculosis infection in Korean high schools. Methods: When a student was identified with active TB, tuberculin skin testing was performed on their classmates and on students in their same school grade. When a student had a positive tuberculin skin tests (TST), they underwent follow-up testing with QuantiFERON-TB Gold In-Tube (QFT). The manufacturer recommended a cut-off of 0.35 IU/mL to determine QFT positivity was applied. Results: A total of 131 pulmonary tuberculosis (TB) patients were included based on the criteria for screening TB contacts in the National Tuberculosis Control Program. Seventy-five (57.2%) students tested smear positive. TST were performed on 7,109 students who were classmates of, or in the same grade as, a TB patient. Of the contacts, 1,231 students (17.3%) were TST positive and they were screened with QFT. Six hundred-sixty-six (55.0%) of the tested students returned a positive QFT result and the rate of positivity was significantly associated with the increasing size of TST indurations (p ＜0.0001). Conclusion: The use of QFT resulted in approximately 45% of TST positive students not being given chemoprophylaxis.

Performance of the tuberculin skin test and interferon-γ release assay for detection of tuberculosis infection in immunocompromised patients in a BCG-vaccinated population

BackgroundInterferon-γ release assay (IGRA) may improve diagnostic accuracy for latent tuberculosis infection (LTBI). This study compared the performance of the tuberculin skin test (TST) with that of IGRA for the diagnosis of LTBI in immunocompromised patients in an intermediate TB burden country where BCG vaccination is mandatory.MethodsWe conducted a retrospective observational study of patients given the TST and an IGRA, the QuantiFERON-TB Gold In-Tube (QFT-IT), at Severance Hospital, a tertiary hospital in South Korea, from December 2006 to May 2009.ResultsOf 211 patients who underwent TST and QFT-IT testing, 117 (55%) were classified as immunocompromised. Significantly fewer immunocompromised than immunocompetent patients had positive TST results (10.3% vs. 27.7%, p 0.001), whereas the percentage of positive QFT-IT results was comparable for both groups (21.4% vs. 25.5%). However, indeterminate QFT-IT results were more frequent in immunocompromised than immunocompetent patients (21.4% vs. 9.6%, p 0.021). Agreement between the TST and QFT-IT was fair for the immunocompromised group (κ = 0.38), but moderate agreement was observed for the immunocompetent group (κ = 0.57). Indeterminate QFT-IT results were associated with anaemia, lymphocytopenia, hypoproteinemia, and hypoalbuminemia.ConclusionIn immunocompromised patients, the QFT-IT may be more sensitive than the TST for detection of LTBI, but it resulted in a considerable proportion of indeterminate results. Therefore, both tests may maximise the efficacy of screening for LTBI in immunocompromised patients.

Response to Rv2628 latency antigen associates with cured tuberculosis and remote infection

Interferon-gamma release assays based on region of difference 1 antigens have improved diagnosis of latent tuberculosis infection (LTBI). However, these tests cannot discriminate between recently acquired infection (higher risk of progression to active tuberculosis) and remote LTBI. The objective of the present study was to evaluate the T-cell interferon-gamma responses to Mycobacterium tuberculosis DosR-regulon-encoded antigens (latency antigens) compared with QuantiFERON TB-Gold In-Tube (QFT-GIT) in subjects at different stages of tuberculosis. A total of 16 individuals with remote LTBI and 23 with recent infection were studied; 15 controls unexposed to M. tuberculosis and 50 patients with active tuberculosis and 45 with cured tuberculosis were also analysed. The results indicated that subjects with remote LTBI showed significantly higher whole-blood interferon-gamma responses to M. tuberculosis latency antigen Rv2628 than did individuals with recent infection, active tuberculosis and controls (p<0.003), whereas no significant differences between these groups were found for other latency antigens tested (Rv2626c, Rv2627c, Rv2031c and Rv2032). The proportion of responders to Rv2628 was five-fold higher among QFT-GIT-positive-individuals with remote infection than among those with recently acquired infection. These data suggest that responses to M. tuberculosis latency antigen Rv2628 may associate with immune-mediated protection against tuberculosis. In contact-tracing investigations, these preliminary data may differentiate recent (positive QFT-GIT results without responses to Rv2628) from remote infection (positive to both tests).

Prospective Comparison of Tuberculin Skin Test and QuantiFERON-TB Gold In-Tube Assay for the Detection of Latent Tuberculosis Infection among Healthcare Workers in a Low-Incidence Setting

We compared the results of the tuberculin skin test with the results of the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay among 182 low-risk healthcare workers. Overall agreement and specificity were high, but the tests did not agree on positive results. Only 2 of 5 positive QFT-GIT assay results could be confirmed with repeat analyses. Indeterminate results were associated with potential immunosuppression.

Short-Term Reproducibility of a Commercial Interferon Gamma Release Assay

Interferon gamma release assays (IGRAs) have been shown to be sensitive and highly specific for the detection of immune memory against Mycobacterium tuberculosis. Little is known about the reproducibility and within-person variability of these assays. Various aspects of short-term reproducibility of a commercial IGRA, the QuantiFERON-TB Gold In-Tube (QFT-IT) assay, were assessed. The QFT-IT assay was performed twice within 3 days in 27 health care workers in Cape Town, South Africa. Two sets of tests were performed by different operators on day 1, and one set was performed on day 3. Aspects such as interoperator, intraoperator, day-to-day variability, and test-retest variability as well as different the storage methods of plasma were investigated. Seventeen of 27 (63%) of participants had at least one positive QFT-IT text; six had discordant results. The agreement of all aspects studied was high, with kappa values between 0.82 and 1.00 for dichotomous measures, and interclass correlations (ICC) of 0.809 to 0.965 were observed for continuous gamma interferon (IFN-gamma) measures. The variability of the magnitude of response was highest comparing measures obtained from individuals on different days (ICC of 0.809). The magnitude of the IFN-gamma responses between assays performed for individual participants was variable, with ranges from 0.03 to 11 IU/ml, resulting is discordant results for five participants. The results indicate that the QFT-IT assay is a robust and highly reproducible assay. Considerable intraindividual variability occurs in the magnitude of IFN-gamma responses, which may influence the interpretation of serial measures.

Detection and Prediction of Active Tuberculosis Disease by a Whole‐Blood Interferon‐γ Release Assay in HIV‐1–Infected Individuals

The sensitivity of whole-blood interferon-gamma release assays to detect or predict active tuberculosis in individuals infected with human immunodeficiency virus type 1 (HIV-1) has as yet not been determined. Methods. In this prospective, longitudinal, single-center study, 830 HIV-1-infected patients underwent testing with the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay. Clinical screening for active tuberculosis was performed at least every 3 months for a median follow-up time of 19 months. At baseline, the QFT-GIT assay yielded positive or indeterminate results in 44 (5.3%) and 47 (5.7%) of the 830 patients, respectively. A positive QFT-GIT assay result occurred at significantly higher frequencies among black individuals than among white individuals (odds ratio, 4.84; 95% confidence interval, 2.25-9.97; P< .001), among patients from Africa than among patients from Austria (odds ratio, 6.57; 95% confidence interval, 2.99-14.25; P< .001), and among patients from high-prevalence countries than among patients from low-prevalence countries (odds ratio, 5.86; 95% confidence interval, 2.41-13.44; P< .001). In patients with indeterminate QFT-GIT assay results, both median actual and nadir CD4(+) T cell counts were significantly lower than in patients with interpretable QFT-GIT assay results (P< .001). At the time of baseline QFT-GIT screening, active tuberculosis was found in 7 (15.9%) of 44 individuals with a positive result and in 1 (0.1%) of 739 patients with a negative result. During the follow-up period, however, progression to active tuberculosis occurred exclusively in patients with a positive QFT-GIT assay result, at a rate of 8.1% (3 of 37 patients; P< .001). Collectively, the sensitivity of the QFT-GIT assay for active tuberculosis was 90.9% (95% confidence interval, 62.3%-98.4%). Our results suggest that the QFT-GIT assay may be a sensitive tool for the detection and prediction of active tuberculosis in HIV-1-infected individuals.

Latent Tuberculosis Diagnosis in Children by Using the QuantiFERON-TB Gold In-Tube Test

The QuantiFERON-TB Gold test was the first blood test to be approved for the diagnosis of latent tuberculosis infection. Although it has been shown to be sensitive and specific in adults, limited data on its performance in children are available. This was a prospective study of children receiving health care in New York, New York. Each child was assessed for risk factors for Mycobacterium tuberculosis infection, underwent tuberculin skin testing, and had a QuantiFERON-TB Gold In-Tube test performed. The concordance between tuberculin skin test and QuantiFERON-TB Gold In-Tube test results was calculated, and the results were analyzed according to the likelihood of exposure to M tuberculosis. Data for 207 children with valid tuberculin skin test and QuantiFERON-TB Gold In-Tube test results were analyzed. There was excellent correlation between negative tuberculin skin test results and negative QuantiFERON-TB Gold In-Tube test results; however, only 23% of children with positive tuberculin skin test results had positive QuantiFERON-TB Gold In-Tube test results. Positive QuantiFERON-TB Gold In-Tube test results were associated with increased likelihood of M tuberculosis exposure, and interferon gamma levels were higher in children with known recent exposure to M tuberculosis, compared with children with older exposure histories. Younger children produced lower interferon gamma levels in response to the mitogen (phytohemagglutinin) control used in the QuantiFERON-TB Gold In-Tube test, but indeterminant results were low for children of all ages. Performance characteristics were similar across all age groups. The QuantiFERON-TB Gold In-Tube test is a specific test for M tuberculosis exposure in children, with performance characteristics similar to those for adults residing in regions with low levels of endemic disease. Concerns about test sensitivity, especially for children <2 years of age, will require additional prospective long-term evaluation.

Interferon Gamma, Interferon-Gamma-Induced-Protein 10, and Tuberculin Responses of Children at High Risk of Tuberculosis Infection

Children in contact with adults with pulmonary tuberculosis (TB) are at risk for infection and disease progression, and chemoprophylaxis may reduce this risk. The identification of infection is based on the tuberculin skin test (TST) and interferon-gamma (INF-gamma) release assays. Other biomarkers such as interferon-gamma-induced-protein 10 (IP-10) may have potential for the diagnosis of latent TB infections. To describe IP-10 concentrations and their association to TST and INF-gamma responses in children recently exposed to adults with smear-positive TB in Brazil and Nepal. : Two surveys using the same design were undertaken to describe TST, INF-gamma, and IP-10 responses in 146 children in Nepal and 113 children in Brazil. The concordance of TST and QuantiFERON-TB gold in-tube (QFT-IT) was high (kappa 0.73 in Brazil and 0.80 in Nepal). IP-10 responses were higher in children with both positive TST and positive QFT-IT (medians 1434 pg/mL in Brazil and 1402 pg/mL in Nepal) and lowest in children with both negative TST and negative QFT-IT (medians 206 pg/mL in Brazil and 81 pg/mL in Nepal). Children with negative TST and positive QFT-IT had higher IP-10 concentrations than children with positive TST but negative QFT-IT. IP-10 is a potential marker to identify latent TB infections that is expressed in large quantities and with good agreement with QFT-IT. The reasons for the discrepant results observed are discussed.

Performance of IFN-Gamma release assays for detection of tuberculosis infection in juvenile I JIA children in biological therapy

Severe TB has recently been described in association with TNF-α blocker therapy. Furthermore conventional tuberculin skin test (TST) may give false-negative results in patients receiving biological therapy. New in vitro test, based on the detection of IFN-γ release by T-cell stimulated with M. tuberculosis specific antigens (IGRA), are available for LTBI diagnosis, promising to be more sensitive and specific than TST. Nevertheless no sufficient evidence on IGRA performance are available in children. The performance of two commercially available IGRAs, ELISPOT-TB (TS-TB) and Quantiferon-TB gold in-Tube (QFT-GIT), were evaluated in comparison with TST in children with rheumatic diseases. In children with positive result clinical and radiological evidence of TB was sought. Nineteen children with JIA were enrolled since November 2006 (median age 13.5 years; range 2–18). Seventeen children were on long term etanercept therapy plus methotrexate (15 mg/m2/week), 1 on infliximab and 1 received adalimubab plus prednisone (0,2 mg/Kg/die). Five children (26%) showed positive TS-TB, QFT-GIT and TST were negative in all children. Both QFT-GIT and TS-TB showed a high percentage of indeterminate results (21% and 16% respectively). None of the 5 patients positive at TS-TB developed active disease, as judged by clinical and radiological findings, at least in a median follow-up period of 16 months (range 9–17 months). Our data suggest that high rate of positive results by TS-TB is expression of non-specific immune reactivity in rheumatic children.

Erhöhte Prävalenz der latenten tuberkulösen Infektion bei Beschäftigten in der Geriatrie?

The incidence of active tuberculosis rises with age. The present study examined whether this results in an increased prevalence of latent tuberculosis infection (LTBI) in healthcare workers (HCW) in geriatric care, using other HCW as comparison group. Data collection was performed by occupational physicians in three hospitals. The LTBI was diagnosed using the QuantiFERON-TB Gold in Tube (QFT-IT), an Interferon-gamma Release Assay (IGRA). The odds ratios adjusted for age, gender and migration were calculated. A total of 454 HCW were examined, 58 (12.8 %) of whom worked at geriatric care units. The prevalence of LTBI was 19.0 % in geriatric care and 10.5 % in other HCW. The age, gender, and migration adjusted odds ratio for a positive QFT-IT was 2.4 (5 % CI 1.1 - 5.2) in health care workers working at geriatric care units. A strong positive association between age and LTBI was observed. The prevalence of LTBI increased from 4.6 % in HCW younger than 30 years to 69.2 % in HCW older than 60 years (p < 0.0005). The data suggest an elevated prevalence of LTBI and therefore an elevated infection risk for HCW engaged in geriatric care. The increase of the LTBI prevalence with age might be explained by longer exposure time at work but also by a cohort effect.

Prevalence of Abnormal Radiological Findings in Health Care Workers with Latent Tuberculosis Infection and Correlations with T Cell Immune Response

BackgroundMore than half of all health care workers (HCWs) in high TB-incidence, low and middle income countries are latently infected with tuberculosis (TB). We determined radiological lesions in a cohort of HCWs with latent TB infection (LTBI) in India, and determined their association with demographic, occupational and T-cell immune response variables.MethodologyWe obtained chest radiographs of HCWs who had undergone tuberculin skin test (TST) and QuantiFERON-TB Gold In Tube (QFT), an interferon-γ release assay, in a previous cross-sectional study, and were diagnosed to have LTBI because they were positive by either TST or QFT, but had no evidence of clinical disease. Two observers independently interpreted these radiographs using a standardized data form and any discordance between them resolved by a third observer. The radiological diagnostic categories (normal, suggestive of inactive TB, and suggestive of active TB) were compared with results of TST, QFT assay, demographic, and occupational covariates.ResultsA total of 330 HCWs with positive TST or QFT underwent standard chest radiography. Of these 330, 113 radiographs (34.2%) were finally classified as normal, 206 (62.4%) had lesions suggestive of inactive TB, and 11 (3.4%) had features suggestive of active TB. The mean TST indurations and interferon-γ levels in the HCWs in these three categories were not significantly different. None of the demographic or occupational covariates was associated with prevalence of inactive TB lesions on chest radiography.Conclusion/SignificanceIn a high TB incidence setting, nearly two-thirds of HCWs with latent TB infection had abnormal radiographic findings, and these findings had no clear correlation with T cell immune responses. Further studies are needed to verify these findings and to identify the causes and prognosis of radiologic abnormalities in health care workers.

Use of an interferon-gamma based assay to assess bladder cancer patients treated with intravesical BCG and exposed to tuberculosis

Objective: Compare the QuantiFERON-TB Gold In-Tube (QFT) assay and the tuberculin skin test (TST) in bladder cancer patients receiving high dose BCG therapy (BCG patients). Design and methods: BCG patients and healthy visitors, both exposed to tuberculosis, were screened with a TST and QFT. Results: QFT-TST correlation was excellent in visitors, but poor in BCG patients. BCG therapy predicted a positive TST ( p < 0.001) but not a positive QFT ( p = 0.35). Discussion: The management of BCG patients was impacted, by measuring the QFT.