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In this cross-sectional study of 284 children and adolescents with clinically or radiologically suspected tuberculosis in a low-endemic country, the QuantiFERON-TB Gold Plus assay specificity, sensitivity, positive predictive value and negative predictive value were 91.5%, 87.3%, 86.4%, and 91.2%, respectively. The specificity was higher than that observed in tuberculin skin tests performed simultaneously, but similar to previous-generation interferon-gamma release assays., Competing Interests: M.T. has received QuantiFERON assays at reduced pricing or free of charge for TB diagnostics projects from the manufacturer (Cellestis/Qiagen) in the past and has received support for conference attendance from Cepheid. The manufacturers had no influence on the study design, data collection, analysis or interpretation, writing of the manuscript, or decision to submit the data for publication. The remaining authors have no other conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The T-SPOT.TB can be read by an ELISPOT plate imager as an alternative to a labor-intensive and time-consuming manual reading, but its accuracy has not been sufficiently discussed to date., Methods: 1,423 test results obtained from manual reading using a microscope and an ELISPOT plate imager were compared. The agreement of qualitative test results was assessed using Cohen's kappa coefficient. The relationship of spot counts was studied using Bland-Altman analysis., Results: The overall percent agreement of the qualitative test results was 95.43% with a kappa coefficient of 0.91. Positive test results with the maximum net spot count of 8 and borderline test results showed relatively high discordance. The agreement of spot counts in panel A, panel B, and nil control was good, and variability did not increase with higher spot counts. On the basis of study findings, a novel strategy for interpreting the test results by an ELISPOT plate imager was proposed., Conclusions: To increase diagnostic accuracy, positive test results with the maximum net spot count of 8 and borderline test results should be manually confirmed. Our strategy could be a practical guide for laboratories to build their own strategies for interpreting the test results by an ELISPOT plate imager., Competing Interests: The authors have declared that no competing interests exist.

The new generation of the IGRA QuantiFERON-TB Gold Plus (QFT-Plus) includes two antigen tubes, TB1 and TB2 which contain specific Mycobacterium tuberculosis peptides designed to stimulate both CD4 and CD8 T-cells. TB1 is designed to target cell mediated responses from CD4 T-cells, while TB2 contains newly designed peptides designed to also stimulate CD8 T-cells. We identified specific CD4 and CD8 T-cell clones that recognize different regions spanning the length of the CFP-10 protein in M. tuberculosisto directly test in QFT-Plus TB1 and TB2 tubes, followed by Interferon-gamma detection by the QFT-Plus ELISA. These clones showed specific responses to the different QFT-Plus tubes, the CD4 T-cell clone showed dose-dependent responses to both TB1 and TB2 tubes, while the CD8 T-cell clones showed specific and targeted responses to the QFT-Plus TB2 tube (>140-fold difference) versus the QFT-Plus TB1 tubes using the QFT-Plus ELISA. This testing provides direct evidence of the specificity of CD8 T-cell mediated response in QFT-Plus TB2 tubes., (Copyright © 2018. Published by Elsevier Ltd.)

Much effort has been made to reduce the cost of LTBI diagnosis with equivalent efficacy and efficiency of interferon-γ release assay (IGRA). This study showed that repeatability, intermediate precision, and accuracy of the Bionote-ELISA were comparable to QFT-ELISA. The Bionote-ELISA could provide the alternative method., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Interferon (IFN)-γ-releasing assay for diagnosing tuberculosis (TB) has shown promise; however, there are only a few reports on usefulness of the QuantiFERON-TB Gold In-Tube test (QFT-GIT) for diagnosing TB vertebral osteomyelitis., Methods: All patients presenting at a tertiary hospital between January 2010 and July 2016 with suspected TB vertebral osteomyelitis were retrospectively enrolled to evaluate the diagnostic performance of QFT-GIT. We used QFT-GIT to measure the IFN-γ response to ESAT-6, CFP-10 and TB7.7., Results: A total of 141 patients were enrolled; 32 (23%) were categorized as having confirmed TB, (1%) as probable TB, 14 (10%) as possible TB and 93 (66%) as not TB. Of these, 16 patients with probable and possible TB were excluded from the final analysis. Chronic granulomas with/without necrosis, acid-fast bacilli stain, M. tuberculosis polymerase chain reaction and cultures for M. tuberculosis were positive in 14 (44%), 12 (38%), 22 (69%) and 28 (88%) patients, respectively, among the 32 patients with confirmed TB. The overall sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio for a positive result, and likelihood ratio for a negative result of the QFT-GIT for TB vertebral osteomyelitis were 91% (95% confidence interval [CI], 75-98%), 65% (95% CI, 54-75%), 50% (95% CI, 42-58%), 95% (95% CI, 86-98%), 2.59 (95% CI, 1.89-3.55) and 0.14 (95% CI, 0.05-0.43), respectively., Conclusion: The QFT-GIT appears to be a useful adjunct test for diagnosing TB vertebral osteomyelitis because the negative test results may be useful for excluding a diagnosis of active TB vertebral osteomyelitis.

Background: Although QuantiFERON-TB Gold In-Tube (QFT-GIT) testing is regularly used to detect infection with Mycobacterium tuberculosis, its utility in a patient population with a low risk for tuberculosis (TB) has been questioned. The following is a cohort study analyzing the efficacy of QFT-GIT testing as a method for detection of active TB disease in low-risk individuals in a neuro-ophthalmologic setting., Methods: Ninety-nine patients from 2 neuro-ophthalmology centers were identified as having undergone QFT-GIT testing between January 2012 and February 2016. Patients were divided into groups of negative, indeterminate, and positive QFT-GIT results. Records of patients with positive QFT-GIT results were reviewed for development of latent or active TB, as determined by clinical, bacteriologic, and/or radiographic evidence., Results: Of the 99 cases reviewed, 18 patients had positive QFT-GIT tests. Of these 18 cases, 12 had documentation of chest radiographs or computed tomography which showed no evidence for either active TB or pulmonary latent TB infection (LTBI). Four had chest imaging which was indicative of possible LTBI. None of these 18 patients had symptoms of active TB and none developed active TB within the follow-up period., Conclusions: Based on our results, we conclude that routine testing with QFT-GIT in a low-risk cohort did not diagnose active TB infection. We do not recommend routine QFT-GIT testing for TB low-risk individuals, as discerned through patient and exposure history, ocular examination, and clinical judgment, in neuro-ophthalmology practice.

Since the beginning of the 21 st century, beside tuberculin skin tests (TST) and chest X-rays, interferon-gamma release assays (IGRA) have become available for diagnosing latent tuberculosis infection. In 2006, the Governmental Institute of Public Health of Lower Saxony (NLGA) established the IGRA in its laboratory, using the QuantiFERON-TB ® Gold In-Tube (QFT). A cohort of 19 309 contact persons who were investigated during contact tracing by local public health departments (LPHD) was analyzed. Within 3 years, 75% of LPHDs in Lower Saxony established the QFT for tuberculosis contact tracing. Between 2007 and 2014 the percentage of contact persons≥15 years of age with initial TST declined from 65.1 to 1.7%. For contact persons<15 years of age, this proportion declined from 81.7% (2007) to 10.1% (2014). The proportion of contact persons who reported a country of birth outside Germany rose from 21.3 to 28.8% between 2008 and 2013. Cases from South Eastern European countries were increasingly reported, seldom from states of the former Soviet Union. 14.1% of the investigated contact persons had a positive QFT. 449 persons with a negative result underwent a second test within 4 months; 4% of these tested positive. Within a period of 8 years, the TST was replaced by the QFT in Lower Saxony, not least because of the modified recommendations for environmental contact tracing in tuberculosis of the German Central Committee against Tuberculosis (DZK). Higher specificity of the QFT and thus fewer X-rays, omission of the second visit for interpreting the TST, and the inappropriate package size of the TST for smaller LPHDs are further arguments in favor for the QFT. But unspecific use of the QFT must be avoided; otherwise, the value of the QFT result declines. The increasing number of contact persons with migration background and the changing countries of origin are a challenge for all who are involved in tuberculosis contact tracing., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: The interferon gamma release assay, TSPOT.TB (TSPOT) can be read by several methodologies, including an Elispot reader or manually by technician. We compared the results from these two counting methods., Methods: Automated and manual TSPOT results among 2481 United States health care workers were compared. Cohen's kappa coefficient was used to determine the inter-rater agreement. Univariate and multiple logistic regression were used to investigate selected variable contributions., Results: No prognostic factors were associated with agreement of TSPOT results between counting methods. Agreement between TSPOT results were 92.3%, 89.5%, 93.0%, and 93.1% at baseline, and at follow-up at 6, 12, and 18 months, respectively. The inter-rater agreement for all test results was good (kappa = 0.71). There was a significant difference between individual technicians kappa coefficients (p < 0.001), but no significant increase in agreement over time for technicians (p = 0.394)., Conclusion: Commercial Elispot readers and manual counts have good agreement of TSPOT results in a low TB burden setting. Levels of agreement differed between individual technicians and automated reader from moderate to very good, indicating borderline results may be misinterpreted due to inter-rater variability. With no latent tuberculosis infection (LTBI) gold standard, it cannot be determined if one TSPOT reading method is better than another., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: This study estimated the incidence of progression to active tuberculosis (TB) among contacts categorized by QuantiFERON(®)-TB Gold in Tube (QFT-GIT) test results and investigated other risk factors related to progression to TB., Methods: Contacts of patients with TB were tested using QFT-GIT and were followed up every 6 months at public health centers to detect clinical progression to TB., Results: Analysis of a retrospective cohort revealed that, of the 625 contacts, 168 were QFT-GIT positive and 457 were negative. Of these, 10 (6%) QFT-GIT-positive and two (0.4%) QFT-GIT-negative contacts progressed to TB during the follow-up period (p < 0.01, statistically significant). Multivariable logistic regression analysis revealed that QFT-GIT positivity (p < 0.01), contact of index patients with many other positive contacts (p < 0.01), household contact (p = 0.014), and untreated latent TB infection (p = 0.047) were independent risk factors for progression to TB during an average follow-up period of 637 days., Conclusions: Progression to TB among QFT-GIT-positive contacts was higher than among QFT-GIT-negative contacts. Other independent risk factors for progression to TB were index cases with more QFT-GIT-positive contacts as well as household contacts.

Introduction: This study is a part of the project on interferon gamma release assays performed in the group of untreated sarcoidosis patients formerly BCG vaccinated. The aim of the study was to assess the rate of positive commercial interferon g release assays in sarcoidosis patients. We discussed the results in the context of hypothesis that M. tuberculosis antigens may play a role in the pathogenesis of sarcoidosis., Material and Methods: 151 patients, mean age 38 ± 10.3, treatment naive, with newly diagnosed pulmonary sarcoidosis were enrolled into the study. All participants underwent QFT-GIT assay. A subgroup of 81 patients underwent also T-SPOT.TB assay., Results: QFT-GIT was positive in 7/151. T-SPOT.TB was positive in 3/81. There were no indeterminate results in both IGRAs. There was no statistically significant relationship between IGRAs results and sarcoidosis parameters such as the radiologic stage, disease duration and the presence of Löfgren's syndrome., Conclusions: In sarcoidosis patients formerly BCG vaccinated, positive rate of IGRAs was 4.6% for QFT-GIT and 3.7% for T-SPOT. TB. We did not find the influence of the selected parameters of sarcoidosis on IGRAs results.

Triggers of indeterminate results from interferon-gamma release assays (IGRA) in patients with rheumatic diseases are still elusive. The aim of the present study was to describe predictors of indeterminate results from IGRA in the field of rheumatology. This cross-sectional study was retrospectively performed by using a database of patients with a request for QuantiFERON-TB Gold-In Tube test (QFT-GIT) for screening of latent tuberculosis infection. The study cohort included 631 patients with rheumatic diseases. All variables influencing indeterminate QFT-GIT results were investigated by logistic regression analysis. The overall frequency of indeterminate IGRA results was 6.8 % (43/631). Those with indeterminate results were more likely to be aged ≥70 years, female, visitors in winter, suffering from systemic lupus erythematosus (SLE), and using sulfasalazine or a tumor necrosis factor (TNF)-α inhibitor. In addition, a longer incubation time of >6 h increased the odds ratio of indeterminate IGRA results. In contrast, the automated ELISA processor, ankylosing spondylitis, and the use of a non-steroidal anti-inflammatory drug decreased the likelihood of indeterminate IGRA results. Lymphopenia, thrombocytopenia, anemia, and hypoalbuminemia were significantly associated with indeterminate IGRA results. Multivariate analysis revealed that SLE, use of sulfasalazine or a TNF-α inhibitor, and a manual ELISA system were significantly independent predictors of indeterminate IGRA results. The proportion of indeterminate results in patients with rheumatic diseases is not infrequent. Careful attention to the pre-analytical conditions should minimize the indeterminate results. Automation of the ELISA process seems to be a promising solution to decrease the rate of indeterminate response.

The performance of QuantiFERON microtube (QFT-MT), using 0.9 mL blood, and QuantiFERON-TB Gold in-tube test (QFT-IT) (3 mL blood), for diagnosing tuberculosis (TB) was compared in children and adults in an endemic setting. In 152 children with suspected TB and 87 adults with confirmed TB, QFT-IT was compared with two QFT-MT concentrations (QFT-MT A and B). Proportions of positive and indeterminate results, interferon (IFN)-γ responses, interassay agreement and sensitivity were assessed. We found similar proportions of indeterminate results, levels of IFN-γ and comparable sensitivity. The interassay agreement was moderate in all children (QFT-IT versus QFT-MT A: 85%, k=0.44 and QFT-IT versus QFT-MT B: 88%, k=0.50) and adults (QFT-IT versus QFT-MT A: 88%, k=0.50 and QFT-IT versus QFT-MT B: 89%, k=0.49). Sensitivity was low (QFT-IT 23%, QFT-MT A 18% and B 19%) in children with confirmed or highly probable TB compared with adults (83%, 86% and 88%, respectively). The QFT-MT test can be reliably performed using less than one-third of the blood volume used in QFT-IT. The reduced volume may be useful for research and future diagnosis of paediatric TB. The poor sensitivity and high indeterminate rate of both IFN-γ release assays in severely ill children, with immature or impaired immunity in an endemic setting, warrants further investigations.