Quantiferon Research Papers - Academia.edu (original) (raw)

Infliximab is an IgG1 antitumor necrosis factor monoclonal antibody that is commonly used to treat inflammatory bowel disease (IBD) and other autoimmune disorders. However, it is known to increase the risk of reactivation of latent tuberculosis (LTBI) due to its capability to disrupt TB granulomas. We describe a case of extrapulmonary TB in a patient with ulcerative colitis who was treated with Infliximab after a negative Quantiferon Test. In addition, we report briefly on the current controversy about the appropriateness, interval, and methods for the repeated screening of latent TB in IBD patients that are treated with antitumor necrosis factor alpha (TNF-α) antibodies.

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- Immunology, Medicine, Inflammatory Bowel Disease, Tuberculosis
- by Evance Godfrey
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- Endocrinology, Pathology, Sociology, Demography
- by Pernille Ravn
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- Rheumatoid Arthritis, Risk assessment, Medicine, Stem Cell Transplantation

Little is known about the QuantiFERON-TB Gold In-Tube Test (QFT) in extreme age groups. The test performance has been reported to be impaired in children and elderly, but reports are diverging. The aim of this study was to evaluate QFT performance in patients with and without Tuberculosis (TB). A retrospective study analysing the results of 18,850 QFT performed in Denmark 2005-2010. The effect of age, sex, localisation of TB, and result of culture on QFT performance (positive, negative and indeterminate results) was determined. Among 383 patients with TB, indeterminate rate was low (3.9%, 15/383). Sensitivity was high (86.1%, 317/368) and not affected by sex or localization of TB disease, but declined with increasing age (p < 0.0001). In children 1-4 years old, sensitivity was high (100%, 9/9). Among 15,709 persons without TB, the indeterminate rate was 5.1% (804/15,709) and significantly higher in infants <1 year (15.6%, 5/32) and elderly >65 years (8.1%, 219/2715) compare...

- by Pernille Ravn
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- Incidence Geometry, Adolescent, Medicine, Tuberculosis
- by Pernille Ravn
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- Immunology, Risk, Brazil, Nepal

We investigated host-derived biomarkers that were previously identified in QuantiFERON supernatants, in a large pan-African study. We recruited individuals presenting with symptoms of pulmonary TB at seven peripheral healthcare facilities in six African countries, prior to assessment for TB disease. We then evaluated the concentrations of 12 biomarkers in stored QuantiFERON supernatants using the Luminex platform. Based on laboratory, clinical and radiological findings and a pre-established algorithm, participants were classified as TB disease or other respiratory diseases(ORD). Of the 514 individuals included in the study, 179(34.8%) had TB disease, 274(51.5%) had ORD and 61(11.5%) had an uncertain diagnosis. A biosignature comprising unstimulated IFN-γ, MIP-1β, TGF-α and antigen-specific levels of TGF-α and VEGF, identified on a training sample set (n = 311), validated by diagnosing TB disease in the test set (n = 134) with an AUC of 0.81(95% CI, 0.76–0.86), corresponding to a sen...

- by Yohannes Belay
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- Immunology, Medicine, Tuberculosis, Disease
- by Morten Ruhwald
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- Immunology, Medicine, Tuberculosis, Mycobacterium tuberculosis
- by Morten Ruhwald
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- Immunology, Nigeria, Adolescent, Medicine
- by Morten Ruhwald
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- Immunology, Risk, Brazil, Nepal
- by Morten Ruhwald
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- Immunology, Adolescent, Medicine, Tuberculosis

Background False negative and indeterminate Interferon Gamma Release Assay (IGRA) results are a well documented problem. Cigarette smoking is known to increase the risk of tuberculosis (TB) and to impair Interferon-gamma (IFN-γ) responses to antigenic challenge, but the impact of smoking on IGRA performance is not known. The aim of this study was to evaluate the effect of smoking on IGRA performance in TB patients in a low and high TB prevalence setting respectively. Methods Patients with confirmed TB from Denmark (DK, n = 34; 20 smokers) and Tanzania (TZ, n = 172; 23 smokers) were tested with the QuantiFERON-TB Gold In tube (QFT). Median IFN-γ level in smokers and non smokers were compared and smoking was analysed as a risk factor for false negative and indeterminate QFT results. Results Smokers from both DK and TZ had lower IFN-γ antigen responses (median 0.9 vs. 4.2 IU/ml, p = 0.04 and 0.4 vs. 1.6, p < 0.01), less positive (50 vs. 86%, p = 0.03 and 48 vs. 75%, p < 0.01) and...

- by Morten Ruhwald
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- Microbiology, Medical Microbiology, Tanzania, Medicine

C-Tb, an ESAT-6/CFP-10-based skin test, has similar sensitivity for active TB compared to tuberculin skin test (TST) and QuantiFERON-TB-Gold-In-Tube (QFT). However, data are limited in children and HIV-infected persons. Asymptomatic South African contacts <5 years (n = 87; HIV-uninfected), or symptomatic individuals of all ages presenting to clinics with suspected TB (n = 1003; 30% HIV-infected) were recruited from eight South African centres. C-Tb and TST were allocated to either forearm double blinded. Samples for QFT were collected in parallel, and test-positivity rates were compared. In participants with microbiologically confirmed TB (n = 75; 45% HIV-infected) sensitivity of C-Tb, TST and QFT were similar (72% versus 75% versus 73%; p>0.5). All 3 tests had similar positivity rates in HIV-infected participants with active TB, however, positivity rates were reduced when CD4 counts were <100 cells/μL. In participants where active TB was excluded (n = 920), C-Tb (41%), TST...

- by Morten Ruhwald
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- Evolutionary Biology, Microbiology, Neuroscience, Immunology
- by Joseph Banda
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- Gastroenterology, Zambia, Medicine, Multidisciplinary
- by Markos Abebe
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- Ethiopia, Medicine, Students, Tuberculosis
- by Markos Abebe
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- Microbiology, Immunology, Medical Microbiology, Infectious Diseases
- by Markos Abebe
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- Ethiopia, Medicine, Students, Tuberculosis
- by Markos Abebe
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- Microbiology, Immunology, Medical Microbiology, Ethiopia
- by Brian Altonen
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- Medicine, Tuberculosis, Internal Medicine, Vaccination
- by Tom h.m. Ottenhoff
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- Medicine, Tuberculosis, Internal Medicine, Mycobacterium tuberculosis
- by Tom h.m. Ottenhoff
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- Immunology, Immune response, Medicine, Tuberculosis
- by Mahbubur Rahman 59
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- Medicine, Applied Economics, Tuberculosis, Cost effectiveness

Latent tuberculosis infection (LTBI) diagnosis in immune-mediated inflammatory diseases is complex because of the patient characteristics and the imperfection of available tests [1]. Functional T-cell assays are exposed to bias at several levels (manufacturing, pre-analytical, analytical and immunological) [2] and, unfortunately, the lack of a gold standard precludes higher diagnostic accuracy. However, the QuantiFERON GOLD In-tube test (QFT; QIAGEN, Hilden, Germany) represents a largely used and modern alternative to the tuberculin skin test. Even if performance specifications of QFT are of great interest (specificity of 99% and sensitivity of 84%) [3], some patients remain with an "indeterminate result" because of failed positive control corresponding to the incapacity of lymphocytes to secrete interferon (IFN)-γ after 24 h of stimulation by phytohemagglutinin A (PHA).

- by Antoine Blancher
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- Immunology, Medicine, Skin Test, Latent Tuberculosis

Background Tuberculosis (TB) remains an important cause of morbidity and mortality in hemodialysis (HD) patients. A gold standard for the diagnosis of latent tuberculosis infection (LTBI) is lacking. Objective The aim of this study was to compare the diagnostic utility of the QuantiFERON-Tuberculosis Gold (QFT-G) test with the tuberculin skin test (TST) in identifying LTBI in patients with end-stage renal disease (ESRD) on HD. Study design The present study had a prospective design. Patients and methods A total of 74 patients with ESRD on HD without active TB and other immunosuppressive conditions were tested for LTBI by the QFT-G test and the TST. Results LTBI, as estimated by the QFT-G test and TST, was detected in 35.1 and 13.5% of the HD patients, respectively; 37.8% of patients were positive for the QFT-G test and/or the TST. There was a poor agreement between QFT-G test and TST results in patients with ESRD on HD (QFT-G test vs. TST: κ=0.25, 95% confidence interval=0.12-0.37). TST was positive in 2.7% of patients when the QFT-G test was negative, and it was negative in 24.3% of patients when the QFT-G test was positive. There was no significant difference in duration of HD or creatinine levels between QFT-G-positive and QFT-G-negative patients (P=0.08 and 0.2, respectively). TST-positive patients had a significantly shorter duration of HD and lower creatinine levels than TST-negative patients (P=0.001 and 0.01, respectively). Conclusion In patients with ESRD and on HD, LTBI cannot be simply ruled out with a negative TST result, but rather a QFT-G test is recommended. Screening and treatment of LTBI should be carried in dialysis patients, aiming to prevent progression to active TB and secondary infection of others.

- by Laila Yousef
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- Gastroenterology, Medicine, Tuberculosis, Internal Medicine

W e report 2 cases of miliary tuberculosis (TB) with late development of a positive result in tuberculin skin test (TST) and QuantiFERON TB In Tube (QFT-GIT) test. The first case was a 2-year-old female of Romanian origin with a recent history of fever and cough. The chest radiograph showed blurred interstitial thickening in the right lung field and the thoracic computed tomography scan confirmed the presence of diffuse nodular opacities. Both TST and QFT-GIT tests had negative results. The screening of family members did not show any case of active TB, but the mother was diagnosed with latent TB. Three samples of gastric aspirate and urine were collected for microscopic identification of acid-fast bacilli, culture and real-time polymerase chain reaction for identification of Mycobacterium tuberculosis. They were all negative. Congenital and acquired immunodeficiencies were excluded. Despite the absence of a known source of infection and the negativity of the TST and interferon-gamma releasing assay tests, because of the epidemiologic data and the strong radiologic suspicion of miliary TB, the patient was started on TB treatment with first-line drugs, with rapid clinical improvement. Two months later, TST and QFT-GIT were repeated and were positive. The computed tomography scan had improved. The girl has been given a total of 12-month anti-TB therapy. She is currently in follow-up. The second case was a Senegalese male, 8 years old, in Italy since 2 years of age. He presented to our hospital with 1 week of fever and fatigue. The chest radiograph showed a bilateral basal nonhomogeneous density. The computed tomography scan highlighted the presence of multiple areas of increased pulmonary parenchymal density with increased bilateral hilar lymph nodes, one of which calcified. No immune deficiencies were found. Because of suspected miliary TB, TST and QFT-GIT were performed and were negative. Nonetheless,

- by Silvia Virano
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- Medicine, Tuberculosis, Miliary Tuberculosis, Quantiferon
- by Rajpal Singh Kashyap
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- Biology, Medicine, Tuberculosis, Population
- by Lazarus Odeny
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- Incidence Geometry, Medicine, Tuberculosis, Internal Medicine
- by Hennie Geldenhuys
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- Incidence Geometry, Adolescent, Medicine, Tuberculosis

Background Tuberculosis (TB) is a communicable disease, transmitted almost exclusively by cough aerosols carrying pathogens of the M. tuberculosis complex. TB continues to be a major public health threat, causing an estimated 10.4 million new cases and 1.3 million deaths from TB globally in 2016. Many more people may have latent tuberculosis infection (LTBI), which may go undetected without further laboratory investigation. The Quantiferon-TB Gold Plus (QFT-Plus) is an Interferon Gamma Release Assay (IGRA) for the identification of LTBI. It detects the cellular immune response to antigens of M. tuberculosis and represents an indirect marker of M. tuberculosis exposure. In January of 2021, the NorthShore University HealthSystem Core Laboratory transitioned from a reference laboratory ELISA-based QFT-Plus test to an in-house DiaSorin LIAISON® QuantiFERON®-TB Gold Plus test. After implementation, we noticed a higher rate of low positive QFT-Plus results (1.3%–5.4%) in our patient popul...

- by ansa mehreen
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- Pathology, Immunology, Environmental Health, Medicine

Objectives: Screening for latent tuberculosis infection (LTBI) diagnosis is mandatory in patients with immune-mediated inflammatory diseases (IMID) requiring biologics. QuantiFERON-TB-Plus (QFT-P), an LTBI diagnostic test, measures IFN-γ after M. tuberculosis-stimulation in TB1 and TB2 tubes in which a "CD4" or a "CD4 and CD8" response is respectively elicited. Aim of this study is to compare the response to QFT-P of IMID-LTBI patients candidates to a new biological therapy vs LTBI-subjects without IMID. Methods: We enrolled 167 subjects: 61 IMID-LTBI and 106 NON-IMID-LTBI. Results: All subjects were mitogen-responders. IFN-γ production was significantly lower in IMID-LTBI-patients compared to NON-IMID-LTBI-subjects. We observed discordant TB1 and TB2 results in 6.5% of IMID-LTBI-patients and in 8% of NON-IMID-LTBI-subjects. Applying a logistic regression analysis, we found that IMID-LTBI patients had a higher probability (TB1 stimulation OR 3.32; TB2 stimulation OR 4.33) to have IFNγ results ≤ 0.7 IU/mL compared to NON-IMID-LTBI-subjects. Interestingly, IMID-treatment did not interfere with the distribution of IFNγ-values. Conclusions: These results indicate that IMID-LTBI-patients have a low IFN-γ response to QFT-P, a high proportion of results ranging in the grey zone and a distribution of IFNγvalues independent from the IMID-treatment. These results are important for the management of LTBI screening in IMID patients.

- by Rossana Scrivo
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- Medical Microbiology, Infectious Diseases, Medicine, Tuberculosis

Background Up to now, there has been no universal consensus on the agreement between the tuberculin skin test (TST) and the QuantiFERON-TB-Gold test (QFT) in the detection of latent tuberculosis infection (LTBI) among high-risk populations. Aims To estimate the agreement between TST and QFT among health care workers (HCWs). Methods A meta-analysis in which all major electronic databases, including Medline, Scopus, Web of Sciences and Ovid, were searched until June 2014. All cross-sectional and cohort studies addressing the agreement between TST and the QFT were included. The extracted data were analysed and the results were reported using random effect models. Results The overall kappa statistic between TST and the QFT was 0.27 [95% confidence interval (CI) 0.22, 0.32] and the adjusted kappa statistic for prevalence and bias was 0.41 (95% CI 0.32, 0.50). The kappa for subjects with and without bacillus Calmette-Guérin (BCG) vaccination was 0.27 (95% CI 0.18, 0.36) and 0.31 (95% CI 0.15, 0.46) respectively. The figures were 0.30 (95% CI 0.16, 0.43) and 0.82 (95% CI 0.74, 0.90) for prevalence-adjusted and bias-adjusted kappa, respectively. Conclusions The overall agreement between TST and QFT in the detection of LTBI among HCWs was poor. After adjusting for the prevalence and bias indices, kappa statistics reached fair agreement. The utility of each of these two tests is dependent on the prevalence and burden of tuberculosis as well as the BCG vaccination status.

- by Ehsan Mostafavi
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- Occupational Medicine, Medicine, Tuberculosis, Internal Medicine

The QuantiFERON-TB Gold in-tube test (QFT-GIT) and the tuberculin skin test (TST) are used to diagnose latent tuberculosis infection (LTBI). However, conclusive evidence regarding the agreement of these two tests among high risk contacts is lacking. This systematic review and meta-analysis aimed to estimate the agreement between the TST and the QFT-GIT using kappa statistics. METHODS: According to the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines, scientific databases including PubMed, Scopus, and Ovid were searched using a targeted search strategy to identify relevant studies published as of June 2015. Two researchers reviewed the eligibility of studies and extracted data from them. The pooled kappa estimate was determined using a random effect model. Subgroup analysis, Egger's test and sensitivity analysis were also performed. RESULTS: A total of 6,744 articles were retrieved in the initial search, of which 24 studies had data suitable for meta-analysis. The pooled kappa coefficient and prevalence-adjusted bias-adjusted kappa were 0.40 (95% confidence interval [CI], 0.34 to 0.45) and 0.45 (95% CI, 0.38 to 0.49), respectively. The results of the subgroup analysis found that age group, quality of the study, location, and the TST cutoff point affected heterogeneity for the kappa estimate. No publication bias was found (Begg's test, p= 0.53; Egger's test, p= 0.32). CONCLUSIONS: The agreement between the QFT-GIT and the TST in diagnosing LTBI among high-risk contacts was found to range from fair to moderate.

- by Ehsan Mostafavi
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- Medicine, Tuberculosis, Internal Medicine, Meta Analysis
- by Ehsan Mostafavi
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- Infectious Diseases, Adolescent, Medicine, Iran

SUMMARY Diagnosis of latent tuberculosis infection (LTBI) is a concern in haemodialysis (HD) patients. Many studies have compared QuantiFERON-TB Gold In-Tube (QFT-GIT) and tuberculin skin test (TST) for detecting LTBI and reported the κ statistic of agreement between QFT-GIT and TST in HD patients. The present study aimed to systematically review this literature and conduct meta-analysis of individual studies that estimated the κ between QFT-GIT with TST among HD patients. All relevant published studies that were available as full-text were obtained by searching Medline (1950), Web of Sciences (1945), Scopus (1973) through May 2016. The κ was re-estimated from the individual studies and pooled using random effect meta-analysis. Subgroup analysis and meta-regression were applied to evaluate the effect of Bacillus Calmette–Guérin (BCG) vaccination, TST cut-off points, quality of studies, sample size and age on variation of κ estimate. Eight studies involving 901 HD patients were inclu...

- by Ehsan Mostafavi
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- Medicine, Tuberculosis, Internal Medicine, Meta Analysis

The collaboration center of meta-analysis research (ccMETA),

- by Ehsan Mostafavi
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- Immunology, Medicine, Multidisciplinary, Tuberculosis

- by Ehsan Mostafavi
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- Medicine, Tuberculosis, Internal Medicine, Meta Analysis

Background: One third of the world's population is thought to have latent tuberculosis infection (LTBI) with the potential for subsequent reactivation of disease. To better characterize this important population, studies comparing Tuberculin Skin Test (TST) and the new interferon-γ release assays including QuantiFERON W-TB Gold In-Tube (QFT-GIT) have been conducted in different parts of the world, but most of these have been in countries with a low incidence of tuberculosis (TB). The aim of this study was therefore to evaluate the use of QFT-GIT assay as compared with TST in the diagnosis of LTBI in Ethiopia, a country with a high burden of TB and routine BCG vaccination at birth.

- by Asrat Mekuria
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- Ethiopia, Medicine, Students, Tuberculosis

Background: While many North American healthcare institutions are switching from Tuberculin Skin Test (TST) to Interferon-gamma release assays (IGRAs), there is relatively limited data on association between occupational tuberculosis (TB) risk factors and test positivity and/or patterns of test discordance. Methods: We recruited a cohort of Canadian health care workers (HCWs) in Montreal, and performed both TST and QuantiFERON-TB Gold In Tube (QFT) tests, and assessed risk factors and occupational exposure. Results: In a cross-sectional analysis of baseline results, the prevalence of TST positivity using the 10 mm cutoff was 5.7% (22/388, 95%CI: 3.6-8.5%), while QFT positivity was 6.2% (24/388, 95%CI: 4-9.1%). Overall agreement between the tests was poor (kappa = 0.26), and 8.3% of HCWs had discordant test results, most frequently TST2/QFT+ (17/388, 4.4%). TST positivity was associated with total years worked in health care, non-occupational exposure to TB and BCG vaccination received after infancy or on multiple occasions. QFT positivity was associated with having worked as a HCW in a foreign country. Conclusions: Our results suggest that LTBI prevalence as measured by either the TST or the QFT is low in this HCW population. Of concern is the high frequency of unexplainable test discordance, namely: TST2/QFT+ subjects, and the lack of any association between QFT positivity and clear-cut recent TB exposure. If these discordant results are indeed false positives, the use of QFT in lieu of TST in low TB incidence settings could result in overtreatment of uninfected individuals.

- by Mihaela Cojocariu
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- Medicine, Multidisciplinary, Canada, Tuberculosis

RationaleIn 2016, a new interferon-gamma release assay (IGRA) was introduced, QuantiFERON-TB Gold Plus (QFT-Plus), claimed to have improved sensitivity in active tuberculosis (TB).ObjectivesThis study aimed to determine the performance of QFT-Plus, compared with previous generation IGRAs and the tuberculin skin test (TST), in children with TB in Europe.MethodsMulticentre, ambispective cohort study within the Paediatric Tuberculosis Network European Trials Group (ptbnet), a dedicated paediatric TB research network comprising >300 members, capturing TB cases <18 years-of-age diagnosed between January 2009 and December 2019.Measurements and main results1001 TB cases from 16 countries were included (mean age (IQR) 5.6 (2.4–12.1) years). QFT-Plus was performed in 358, QFT Gold in-Tube (QFT-GIT) in 600, T-SPOT.TBin 58 and TST in 636 cases. The overall test sensitivities were: QFT-Plus 83.8% (95% CI 80.2% to 87.8%), QFT-GIT 85.5% (95% CI 82.7% to 88.3%), T-SPOT.TB77.6% (95% CI 66.9% ...

- by María Espiau
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- Medicine, Tuberculosis, Internal Medicine, Thorax

The mass influx of immigrants from tuberculosis-endemic countries into Israel was followed by a considerable increase in the incidence of tuberculosis (TB). All contacts of active TB patients are obliged to be screened by tuberculin skin tests (TST) and, if found positive, prophylactic treatment is considered. To assess the utility of interferon-gamma (IFNγ)-release assay with a prolonged follow-up in preventing unnecessary anti-TB therapy in individuals with suspected false positive results. Between 2008 and 2012 the QuantiFERON TB gold-in-tube test (QFT-G) was performed in 278 sequential individuals who were mostly TST-positive and/or were in contact with an active TB patient. In all, whole blood was examined by the IFNγ-release assay. We correlated the TST diameter with the QFT-G assay and followed those patients with a negative assay. The QFT-G test was positive in only 72 (42%) of all 171 TST-positive individuals. There was no correlation between the diameter of TST and QFT-G p...

- by Daniel Weiler-Ravell
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- Incidence Geometry, Medicine, Israel, Immigrants and Emigrants

The clinical utility of the QuantiFERON-CMV (QFN-CMV) assay in heart transplant recipients was assessed. Forty-four cytomegalovirus (CMV)-seropositive patients were enrolled: 17 received antiviral prophylaxis, and 27 were managed preemptively. CMV-DNAemia monitoring was performed by the use of a quantitative real-time PCR assay. The QFN-CMV assay was retrospectively performed on blood samples collected at five posttransplant time points. A higher proportion of patients with an indeterminate QFN-CMV result after the suspension of prophylaxis than of patients who showed a global T-cell responsiveness developed CMV infection ( = 0.036). Patients who reconstituted a CMV-specific response following the first CMV-DNAemia-positive result (42.9%) showed a median CMV-DNAemia peak 1 log of magnitude lower than that seen with patients with indeterminate results, and all controlled viral replication spontaneously. The 25% of patients with an indeterminate result developed CMV disease. In the pr...

- by Tamara Ruiz Merlo
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- Immunology, Medicine, Clinical Microbiology, Biological Sciences

Objectives To evaluate the accuracy of the QuantiFERON-TB Gold assay (QFT-IT) in children with suspected active or latent TB infection (LTBI). Methods A retrospective study was conducted on 621 children (0-14 years old) evaluated for TB infection or disease. Following clinical assessment, children were tested with the QFT-IT assay. Results Among the 140 active TB suspects, we identified 19 cases of active disease. The overall sensitivity for active TB was 87.5%, ranging from 62.5% in children 25-36 months old to 100% in children older than 49 months. The overall specificity for active TB was 93.6%. Among the 481 children tested for LTBI screening, 38 scored positive and all but 2 had at least one risk factor for TB infection. Among the 26 children with indeterminate results, bacterial, viral or fungal pneumonia were later diagnosed in 11 (42.3%) cases and non-TB related extra-pulmonary infections in 12 (46.1%). Conclusions Our results indicate that the children's response to QFT-IT associates to active TB and risk factors for LTBI. Moreover, we show that mitogen response is also found in children of 1 year of age, providing support for QFT-IT use also in young children.

- by Antonella Zumbo
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- Adolescent, Medicine, Multidisciplinary, Tuberculosis

The diagnosis of a latent tuberculosis infection (LTBI) is based on detection of immunity against Mycobacterium tuberculosis (Mtb). The tuberculin skin test (TST), the Quantiferon (QFT) and a prolonged lymphocyte stimulation test using either ESAT-6/CFP-10 (LST-EC) or PPD (LST-PPD) were evaluated in a cohort of 495 individuals, suspected to have LTBI, in a low endemic country. While the TST and LST-PPD were both positive in the majority (75%) of individuals, only one third responded in the LST-EC and in the QFT. The choice for LTBI treatment was significantly associated with ESAT6/CFP10 recognition, however the LST-EC detected considerably more individuals (21%) with immunity against Mtb, who might also be at risk for development of active TB, although none of them did during follow up. Follow-up for 2 years showed 7% conversions and 32% reversions for the QFT. The LST-EC showed higher conversion rates (~45%), although the percentage of individuals positive in the LST-EC did not change significantly within the follow-up period. LTBI treatment did not alter immune recognition of Mtb antigens. In conclusion, the sensitivity of tests for detection of cellular immunity to Mtb specific antigens depends on test methodology and may vary considerably over time in a low endemic region.

- by Corine Prins
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- Immunology, Medicine, Tuberculosis, Mycobacterium tuberculosis

Recently, interferon-c release assays (IGRA) for specific diagnosis of Mycobacterium tuberculosis infection have become available. In recent UK tuberculosis (TB) guidelines, it has been advised to screen for latent M. tuberculosis infection using the tuberculin skin test (TST), followed by IGRA if the TST is positive. Since TST can boost immune responses to tuberculin, the present authors evaluated whether TST administration affects the result of QuantiFERON1-TB Gold in-tube (QFT-GIT), a whole blood-based IGRA. QFT-GIT was performed on the day of TST administration and the day of reading in 15 TSTnegative subjects, 46 TST-positive subjects with recent or remote exposure to M. tuberculosis and five cured TB patients. No systematic boosting of QFT-GIT responses from negative to positive was observed. Only in a few TST-positive persons did TST enhance pre-existing QFT-GIT responses. Screening for latent Mycobacterium tuberculosis infection using tuberculin skin testing followed by interferon-c release assays on the day of reading is a reliable approach, as the specificity of QuantiFERON1-TB Gold in-tube is not affected by prior tuberculin skin test administration.

- by Corine Prins
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- Immunology, Immune response, Medicine, Mycobacterium tuberculosis

The sensitivities of various gamma interferon release assays (IGRAs) for the detection of past latent Mycobacterium tuberculosis infection are not known. In this study, we aimed to assess the effects of various IGRA formats and in vitro incubation periods on test outcome. The results of the tuberculin skin test (TST) were compared with those of the QuantiFERON-TB Gold in-tube (QFT-GIT) test, an overnight enzyme-linked immunospot assay (ELISPOT), and a 6-day lymphocyte stimulation test (LST) by using the same M. tuberculosis-specific peptides and samples from 27 TST-positive persons with a history of exposure to M. tuberculosis, 4 patients cured of tuberculosis (TB), and 9 TST-negative controls. Among the TST-positive persons, the LST was more frequently positive (92%; P < 0.01) than either the QFT-GIT test (33%) or ELISPOT (46%). While good agreement was observed between the QFT-GIT test and ELISPOT (‫؍‬ 0.71) and between TST and LST (‫؍‬ 0.78), the agreement between TST or LST, on the one hand, and the QFT-GIT test or ELISPOT, on the other, was poor. These data indicate that the QFT-GIT test and overnight ELISPOT are less sensitive for the detection of past latent TB than the 6-day LST. The observed discrepancies between these IGRAs are most likely related to differences in incubation periods. Whether TST-positive persons with positive LST results but negative QFT-GIT and ELISPOT results are at risk for the development of TB needs to be elucidated before short-incubation IGRAs can be used for the screening of individuals for latent TB before immunosuppressive treatment.

- by Corine Prins
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- Immunology, Immune response, Medicine, Tuberculosis

The tuberculin skin test (TST) was compared with QuantiFERON-TB Gold in-tube (QFT-GIT) test for the diagnosis of tuberculosis in non-Mycobacterium bovis BCG-vaccinated military personnel. Among subjects positive by TST, 44.4% of recruits were positive by QFT-GIT compared with 11.5% subjects tested after missions abroad, suggesting that most TST conversions in the latter group were caused by nontuberculous mycobacteria.

- by Corine Prins
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- Immunology, Medicine, Prospective studies, Mycobacterium tuberculosis

Background: The new QuantiFERON Gold Plus (QFT+) assay is used for diagnosing tuberculosis (TB) infection and has 2 phlebotomy methods: direct (QFT + D) and single tube transfer (QFT + T). Little data is available on how the TB incidence in the country of birth (COB) of healthcare workers (HCWs) can impact the assay results. Methods: QuantiFERON Gold In-Tube (QFT-G), QFT + D and QFT + T assays were obtained from a single blood draw and compared for HCWs annually tested for TB infection. HCWs COB was ranked as: high (≥150 per 100,000), medium (20-149), and low TB incidence (< 20 TB cases). Results: In 265 HCWs, QFT-G/+D/+T results from medium TB incidence COB (15.6%, 16.9% and 22.1%) were more likely to be positive than high (9.7%, 11.8% and 16.1%) or low incidence COB (6.3%, 8.4% and 10.5%). Agreement between assay results for high, medium and low TB incidence COB were: 95.7%, 83.1%, and 95.8% between QFT-G/QFT + D (p = 0.003), 91.4%, 88.3% and 95.8% between QFT-G/QFT + T (p = 0.187), and 91.4%, 76.6%, and 91.6% between QFT + D/QFT + T (p = 0.005). Conclusion: Lower agreement and a higher proportion of positivity were found in QFT-G/+D/+T results in individuals from medium TB incidence COB. QFT + may be more sensitive than QFT-G in HCWs from medium TB incidence COB.

- by Edward A Graviss
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- Incidence Geometry, Medicine, Tuberculosis, Quantiferon
- by Kandi Muze
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- Endocrinology, Pathology, Sociology, Demography
- by Michele Tameris
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- Immunology, Medicine, Tuberculosis, Mycobacterium tuberculosis
- by Mario Vaz
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- Immunology, Biology, Adolescent, Medicine
- by Hamida M Amer
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- Pathology, Mathematics, Immunology, Pure Mathematics