Association of Mycobacterium tuberculosis infection test results with risk factors for tuberculosis transmission.

Background: Close contacts infected with Mycobacterium tuberculosis are at high risk of tuberculosis (TB) disease and a priority for preventive treatment. Three tests measure infection: two interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST). The objective of our study was to assess the association of positive test results in contacts with infectiousness of the presumed TB source case. Methods: Contacts in a cohort study at 10 United States sites received both IGRAs (QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB (T-SPOT)) and TST. We defined test conversion as negative for all tests at baseline and positive for at least one on retest. Risk ratios (RR) and 95% confidence intervals (CI) assessed association of positive test results with increased infectiousness of the TB case-defined as acid-fast bacilli (AFB) on sputum microscopy or cavities on chest radiographs- and contact demographics. Results: Adjusted for contacts' age, nativity, sex, and race, IGRAs (QFT-GIT RR = 6.1, 95% CI 1.7-22.2; T-SPOT RR = 9.4, 95% CI 1.1-79.1), but not TST (RR = 1.7, 95% CI 0.8-3.7), were more likely to convert among contacts exposed to persons with cavitary TB disease. Conclusions: Because IGRA conversions in contacts are associated with infectiousness of the TB case, their use may improve efficiency of health department contact investigations by focusing efforts on those likely to benefit from preventive treatment in the United States.

Mycobacterium tuberculosis Infection among 1,659 Silicosis Patients in Zhejiang Province, China.

Silicosis is a well-established risk factor for Mycobacterium tuberculosis infection. This study aimed to estimate the burden and risk factors of M. tuberculosis infection. Silicosis patients from Zhejiang Province were screened for M. tuberculosis by sputum culture, chest radiographs, whole-blood gamma interferon (IFN-γ) release assay (QuantiFERON-TB Gold In-Tube [QFT-GIT]), and tuberculin skin test (TST). Potential risk factors for M. tuberculosis were identified. Data for 1,659 patients were obtained from 1,684 participants. Of these, 1,656 (99.8%) were men, and the average age was 58 (54 to 63) years. The prevalence of active tuberculosis (ATB) was 6,340/100,000 (6.34%) people; the proportion of patients with latent tuberculosis infection (LTBI) was 50.6%. Age (odds ratio [OR] = 1.059, 95% confidence interval [CI] = 1.020 to 1.099, P = 0.003), being underweight (OR = 2.320, 95% CI = 1.057 to 5.089, P = 0.036), and having a history of exposure to TB patients (OR = 4.329, 95% CI = 1.992 to 9.434, P < 0.001) were associated with ATB; BCG vaccination could reduce ATB risk in silicosis patients (OR = 0.541, 95% CI = 0.307 to 0.954, P = 0.034). Among patients without ATB, the QFT-GIT positivity rate was 40.5%, which was affected by silicosis severity, while that of TST was 57.2%. BCG vaccination was an independent factor for LTBI risk reduction (OR = 0.612, 95% CI = 0.468 to 0.801, P < 0.001). The quantitative results of QFT-GIT decreased with silicosis stage (H = 6.037; P = 0.048). In conclusion, M. tuberculosis prevalence was high in silicosis patients. BCG vaccination reduced the risk of both ATB and LTBI in silicosis patients. IMPORTANCE This study evaluated the prevalence of Mycobacterium tuberculosis infection in silicosis patients in mainland China and identified the potential risk factors for both active tuberculosis (ATB) and latent tuberculosis infection (LTBI). We believe that our study makes a significant contribution to the literature because we demonstrated that M. tuberculosis prevalence was high among silicosis patients. BCG vaccination was an independent factor that reduced the risk of M. tuberculosis infection in patients with silicosis. Furthermore, we show that the prevalence of LTBI in patients with silicosis may have been underestimated by immunological detection methods. This study can help to identify targeted subgroups prioritized for M. tuberculosis control and to reduce the risk of disease development.

Performance of LTBI Screening in Patients with Rheumatic Diseases Using Two Different Interferon-Gamma Releasing Assays.

BACKGROUND: To evaluate the concordance between QuantiFERON-TB Gold in-tube test (QFT-GIT) and T-SPOT.TB test (T-SPOT) for the screening of latent tuberculosis infection (LTBI) in patients with rheumatic diseases (RDs). METHODS: Patients diagnosed as rheumatic diseases (RDs) with clinical indications for test of interferon gamma release test (IGRA) were prospectively recruited from 2019 to 2020. The consistency of QFT-GIT and T-SPOT was assessed by Kappa analysis and the factors associated with the indeterminate results were explored by multivariable logistic analysis. RESULTS: A total of 108 patients with RDs were enrolled, including 64 patients with systemic lupus erythematosus (SLE) and 44 with inflammatory arthritis (26 with rheumatoid arthritis (RA) and 18 with ankylosing spondylitis (AS)). Poor concordance was confirmed between QFT-GIT and T-SPOT results in patients with SLE (K = 0.175, 95% confidence interval [95% CI] [-0.06, 0.40], p < 0.001), whereas concordance was moderate in patients with inflammatory arthritis (K = 0.539, 95% CI [0.11, 0.88], p < 0.001). Among SLE patients, the ratio of indeterminate results in detecting LTBI was significantly higher by QFT-GIT than by T-SPOT (18.8% vs. 4.7%, p = 0.013), while the statistical difference was not achieved in patients with inflammatory arthritis. The multivariable logistic analysis identified that the presence of lower lymphocyte counts (odds ratio [OR] = 0.81, 95% CI [0.68, 0.97], p = 0.020) was the independent predictor of an indeterminate result of the QFT-GIT in SLE patients. CONCLUSIONS: In patients with RDs, the result of screening of LTBI was more definitive by T-SPOT test than QFT, and the concordance was poor especially in the setting of SLE.

Analysis of the diagnostic efficacy of the QuantiFERON-TB Gold In-Tube assay for preoperative differential diagnosis of spinal tuberculosis.

Background: Differential diagnosis of spinal tuberculosis is important for the clinical management of patients, especially in populations with spinal bone destruction. There are few effective tools for preoperative differential diagnosis in these populations. The QuantiFERON-TB Gold In-Tube (QFT-GIT) test has good sensitivity and specificity for the diagnosis of tuberculosis, but its efficacy in preoperative diagnosis of spinal tuberculosis has rarely been investigated. Method: A total of 123 consecutive patients with suspected spinal tuberculosis hospitalized from March 20, 2020, to April 10, 2022, were included, and the QFT-GIT test was performed on each patient. We retrospectively collected clinical data from these patients. A receiver operating characteristic (ROC) curve was plotted with the TB Ag-Nil values. The cutoff point was calculated from the ROC curve of 61 patients in the study cohort, and the diagnostic validity of the cutoff point was verified in a new cohort of 62 patients. The correlations between TB Ag-Nil values and other clinical characteristics of the patients were analyzed. Results: Of the 123 patients included in the study, 51 had confirmed tuberculosis, and 72 had non-tuberculosis disease (AUC=0.866, 95% CI: 0.798-0.933, P<0.0001). In patients with spinal tuberculosis, the QFT-GIT test sensitivity was 92.16% (95% CI: 80.25%-97.46%), and the specificity was 67.14% (95% CI: 54.77%-77.62%). The accuracy of diagnostic tests in the validation cohort increased from 77.42% to 80.65% when a new cutoff point was selected (1.58 IU/mL) from the ROC curve of the study cohort. The TB Ag-Nil values in tuberculosis patients were correlated with the duration of the patients' disease (r=0.4148, P=0.0025). Conclusion: The QFT-GIT test is an important test for preoperative differential diagnosis of spinal tuberculosis with high sensitivity but low specificity. The diagnostic efficacy of the QFT-GIT test can be significantly improved via application of a new threshold (1.58 IU/mL), and the intensity of the QFT-GIT test findings in spinal tuberculosis may be related to the duration of a patient's disease.

Prevalence and risk factors for latent tuberculosis among diabetes patients in Taiwan: A cross-sectional study.

INTRODUCTION: Diabetes mellitus (DM) is a known risk factor for tuberculosis (TB), leading to an approximate three-fold higher risk of developing active TB. However, epidemiological studies on the prevalence of latent TB infection (LTBI) in DM patients are lacking. In this study, we investigated the presence of LTBI and determined risk factors for LTBI in DM patients. METHODOLOGY: We conducted a cross-sectional study at Taipei Medical University-Shuang Ho Hospital in northern Taiwan. The study population comprised DM patients (aged 20-70 years) attending a metabolism outpatient clinic between February 2011 and February 2013, excluding patients who were suspected or confirmed to have active TB. Venous blood samples were drawn from patients to detect LTBI using the QuantiFERON-TB Gold In-Tube (QFT-GIT) method. RESULTS: We enrolled 1120 patients with DM. The QFT-GIT showed positive results for 241 people (21.5%) and negative results for 879 people (78.5%). The mean age at QFT-GIT positivity was 58.2 years, which was significantly dissimilar to the mean age at QFT-GIT negativity, which was 55.0 years (p < 0.001). Multivariate logistic regression indicated that the trend of QFT-GIT positivity increased after the age of 50 years. Effective glycemic control did not differ significantly between QFT-GIT-positive and -negative patients. Moreover, men were predominant were predominant in both QFT-GIT-positive and -negative patients. CONCLUSIONS: More than one-fifth of DM patients have LTBI. Among the DM patients, those older than 50 years may have a higher risk of LTBI. Moreover, effective glycemic control did not differ significantly in patients with LTBI.

Screening of latent tuberculosis infection among patients with diabetes mellitus from a high-burden area in Brazil.

Although several cohort studies have raised the important association between diabetes mellitus (DM) and latent tuberculosis infection (LTBI), evidences are limited and controversial. Furthermore, it is well documented that the poor glycemic control may exacerbate the risk for active TB. Thus, the monitoring of diabetic patients living in high-incidence areas for TB is an important concern in views of available diagnostic tests for LTBI. In this cross-sectional study, we estimate the association of DM and LTBI among diabetic patients classified as type-1 DM (T1D) or type-2 DM (T2D) living in Rio de Janeiro, RJ, Brazil - considered a high TB burden region of these country. Non-DM volunteers were included as endemic area healthy controls. All participants were screened for DM using glycosylated-hemoglobin (HbA1c) and for LTBI using the QuantiFERON-TB Gold in Tube (QFT-GIT). Demographic, socioeconomic, clinical and laboratorial data were also assessed. Among 553 included participants, 88 (15.9%) had QFT-GIT positive test, of which 18 (20.5%) were non-DM, 30 (34.1%) T1D and 40 (45.4%) T2D. After adjustments for potential baseline confounders, age, self-reported non-white skin color and an active TB case in the family were significantly associated with LTBI among the studied population by using a hierarchical multivariate logistic regression analysis. Additionally, we verified that T2D patients were able to produce significant increased interferon-gamma (IFN-γ) plasma levels in response to Mycobacterium tuberculosis-specific antigens, when compared to non-DM individuals. Altogether, our data showed an increased prevalence of LTBI among DM patients, albeit non-statistically significant, and point out to important independent factors associated with LTBI, which deserve attention in monitoring patients with DM. Moreover, QFT-GIT test seems to be a good tool to screening LTBI in this population, even in a high TB burden area.

Frequency and Factors of Indeterminate QuantiFERON-TB Gold In-Tube and QuantiFERON-TB Gold PLUS Test Results in Rheumatic Diseases.

We compared the results and differences of indeterminate rates between the QuantiFERON-TB Gold In-Tube (QFT-GIT) and QuantiFERON-TB Gold PLUS (QFT-PLUS) tests in patients with rheumatic diseases and analyzed the associated factors. Data of patients with rheumatic diseases who had undergone the QFT-GIT or QFT-PLUS test were used, and information regarding patient demographics, primary diagnosis, laboratory results, and medications was collected. Furthermore, indeterminate result rates of the patient cohort and healthy controls were also compared. A total of 177 (43.4%) and 231 (56.6%) patients had undergone QFT-GIT and QFT-PLUS tests, respectively. Among them, four (2.3%) and seven (3.0%) patients had indeterminate results, which did not differ between the QFT-GIT and QFT-PLUS groups. Indeterminate results were significantly higher among patients with rheumatic diseases than in healthy controls (2.7% vs. 0.2%, p < 0.001). Multivariate logistic regression revealed that the lymphocyte count (hazard ratio (HR) 0.998, 95% confidence interval (CI) 0.997, 1.000; p = 0.012) and albumin level (HR 0.366, 95% CI 0.150, 0.890; p = 0.027) were predictive of indeterminate results. A lymphocyte count of ≤810/mm3 and an albumin level of ≤3.7 mg/dL were capable of discriminating between indeterminate and determinate results. The QFT-GIT and QFT-PLUS tests have comparable diagnostic performances in patients with rheumatic diseases. Decreased lymphocyte and albumin levels contribute to indeterminate results.

Comparison of QuantiFERON-TB Gold Plus and QuantiFERON-TB Gold In-Tube tests for patients with active and latent tuberculosis: A prospective cohort study.

INTRODUCTION: We aimed to determine the diagnostic performance and clinical value of the QuantiFERON-TB Gold In-Tube (QFT-GIT) and QuantiFERON-TB Gold Plus (QFT-Plus) tests in patients with active tuberculosis (TB) or latent TB infection (LTBI). METHODS: We prospectively enrolled 140 patients, including 63 with active TB and 77 with LTBI, between March 2017 and October 2018. QFT-GIT and QFT-Plus were performed simultaneously in all subjects. RESULTS: QFT-Plus and QFT-GIT test results showed significant agreement, in both active TB and LTBI patients, in terms of the interferon-γ concentration and interpretation result. QFT-Plus had higher sensitivity than QFT-GIT for predicting active TB (82.5% vs. 77.8%) and showed fewer false-negative and indeterminate results in both active TB and LTBI patients due to its "TB2 tube". The QFT-Plus TB2-TB1 value was higher in the active TB group than in the LTBI group. The QFT-Plus TB1-Nil and TB2-Nil values were useful in predicting remote LTBI, rather than recent LTBI. CONCLUSIONS: QFT-Plus showed good agreement with QFT-GIT in both active TB and LTBI patients, and higher sensitivity for predicting active TB than QFT-GIT. The QFT-Plus TB2 tube results, which reflect CD8+ T cell immunity, may improve predictive accuracy and detection of the immune response associated with active TB and LTBI.

Features of indeterminate results of QuantiFERON-TB Gold In-Tube test in patients with haematological malignancies.

BACKGROUND AND AIMS: The application of QuantiFERON-TB Gold in-Tube (QFT-GIT) in patients with haematological malignancies (HMs) has not been well studied. Therefore, we aimed to investigate the features of patients with HMs whose QFT-GIT results were indeterminate. METHODS: This study enrolled patients with HMs for the analysis of QFT-GIT tests and additional 2-year follow-up. The characteristics and predictors of QFT-GIT indeterminate results were identified. Mycobacterium tuberculosis (TB) incidence rate (IR) and incidence rate ratio (IRR) were also investigated. RESULTS: Of 89 participants, 27 (30.3%) had QFT-GIT indeterminate results. The QFT-GIT indeterminate patients were characterized with the diagnosis of leukaemia (63.0% versus 32.3%, p = 0.044), abnormal white blood count (WBC) (88.9% versus 14.5%, p = 0.001), abnormal lymphocyte percentage (81.5% versus 14.5%, p = 0.001) and lower lymphocyte count (×109/l) (0.5 versus 2.2, p = 0.000) when compared with those with determinate results. Meanwhile, abnormal WBC [odds ratios (OR): 15.18, p = 0.003] and lymphocyte percentage (OR: 6.90, p = 0.033) were predictors of indeterminate results. One patient with the QFT-GIT indeterminate status and high interferon-γ level of negative control result developed active TB with a TB IR of 18.5 per 1000 person-years and an IRR of 0.1 (95% confidence interval, 0.01-0.71) when compared with positive QFT-GIT patients without prophylaxis treatment. CONCLUSION: Abnormal ranges of WBC and lymphocyte differential count percentage were independent predictors useful to determine the optimal timing of implementing QFT-GIT test in patients with HMs.

Predictors of Discordant Tuberculin Skin Test and QuantiFERON-TB Gold In-tube Results in Eastern China: A Population-based, Cohort Study.

BACKGROUND: Discordance between the QuantiFERON-TB Gold In-tube (QFT) and tuberculin skin test (TST) is not well understood. We aimed to identify the factors that determine discordance between the TST and QFT when compared to either TST+QFT+ or TST-QFT- results in a medium tuberculosis (TB) burden setting. METHODS: We conducted a population-based study in Eastern China and administered TSTs and QFTs to participants. We calculated kappa values while constructing multivariable logistic regression models to evaluate predictors of test discordance. We analyzed the predictive value of discordant and concordant test results for progression to TB over 6 years of follow-up. RESULTS: Overall, 5405 participants were enrolled; 2043 (37.8%) and 1104 (20.4%) were TST and QFT positive, respectively. There was fair agreement between the TST and the QFT (kappa values between 0.30-0.39 at different TST cutoffs). Agreement was lower among participants vaccinated with Bacillus Calmette-Guerin (BCG; κ, 0.17 versus 0.47 in nonvaccinated participants). TST+QFT- results were associated with decreasing age, smoking, undiagnosed diabetes, and BCG vaccination (adjusted odds ratio, 1.45; 95% confidence interval [CI], 1.11-1.90). TST-QFT+ results were associated with increasing age, male sex, smoking, and diagnosed diabetes. Compared to participants with TST-QFT- results, QFT+ and TST+QFT+ participants were 6.3 (95% CI, 1.9-20.4) and 7.5 (95%CI, 2.3-25.1) times more likely to progress to TB, respectively. CONCLUSIONS: In this population-based study of over 5000 participants from a medium TB burden region, the test agreement between QFT and TST was fair overall and we found multiple novel predictors of discordant QFT/TST results. QFT provides a substantial improvement to the TST among these populations and was multi-fold better at predicting progression to TB.

QuantiFERON®-TB Gold In-Tube test can be used for screening latent tuberculosis before biological treatment in a Bacille Calmette-Guérin (BCG)-vaccinated country: the HUR-BIO single-center real-life results.

OBJECTIVES: The Turkish population is vaccinated with Bacille Calmette-Guérin (BCG), and the BCG vaccination decreases the specificity of the tuberculin skin test (TST). The purpose of this study was to investigate the incidence of active tuberculosis (TBC) among rheumatic patients who were screened only with the QuantiFERON®-TB Gold In-Tube (QFT-GIT) test for latent TBC prior to biological treatment. METHODS: The Hacettepe University Biological Database (HUR-BIO) was used for latent TBC assessment. Consecutive patients were evaluated from July 2015 to October 2016 by a questionnaire that included the patients' demographic characteristics, treatment history, and symptoms of active TBC. A total of 664 patients were interviewed by physicians. TBC statuses of the 671 non-interviewed patients were checked from the Turkish National Tuberculosis Registry records. Mean TBC incidence per year was calculated for anti-tumor necrosis factor-alpha (TNF-α) agents. RESULTS: A total of 1335 (58.2% female) patients with the mean age of 44.2 ± 12.9 years were included. Of the patients, 836 (62.6%) had spondyloarthropathy, 432 (32.4%) had rheumatoid arthritis, and 67 (5%) had other rheumatologic diseases. The total biological drug exposure was 2292 patient-years (2043 patient-years for anti-TNF-α, 249 patient-years for non-TNF-α inhibitors). Positive and indeterminate QFT-GIT results were found in 258 (19.3%) and 23 (1.7%) patients, respectively. The median follow-up time after the onset of biological agent was 19.4 months (IQR = 29.5). Pulmonary TBC was found in 3 (0.2%) of the 1335 patients. The annual incidence of TBC was 147/100,000 patient-years for all TNF-α inhibitors (249/100,000 and 123/100,000 patient-years for QFT-GIT-positive and negative patients, respectively). CONCLUSIONS: TBC incidence increased by nearly seven times the Turkish national TBC incidence. The QFT-GIT Test appears acceptable to determine latent TBC before biological agent use. Consequently, the QFT-GIT Test can be appropriately used in BCG-vaccinated countries. Key Points • Our study contributes to filling the gap in the literature by reflecting real-life data about TBC frequency after QFT-GIT use in patients receiving biological agents. • The frequency of active TBC will remain within acceptable limits when only QFT-GIT is used in the screening of latent TBC prior to the use of biological agents in a population where the majority are vaccinated with BCG. • Using the QFT-GIT alone for latent TBC screening prior to biologic treatment in countries with high BCG vaccination rates reduces the number of patients needing isoniazid (INH) treatment.

Latent Tuberculosis Infection Increases in Kidney Transplantation Recipients Compared With Transplantation Candidates: A Neglected Perspective in Tuberculosis Control.

BACKGROUND: The prevalence and incidence of latent tuberculosis infection (LTBI) in patients with kidney transplantation remain unclear. METHODS: In this prospective study, we enrolled kidney transplantation candidates (KTCs) and recipients (KTRs) from 2014 to 2018. We defined LTBI as a positive result of QuantiFERON-TB Gold In-tube (QFT). We analyzed the predictors for LTBI acquisition and followed up on QFT assay test for 2 years among those initially without LTBI. RESULTS: Of 425 patients enrolled, 305 (71.8%) patients belonged to the KTC group and 120 (28.2%) to the KTR group. The initial QFT showed positive results in 32 (10.5%) and 24 (20.0%) patients in the KTC and KTR groups, respectively (P = .009). The QFT response value in patients with LTBI was higher in the KTR group than in the KTC group (1.85 vs 1.06 IU/mL, P = .046). Multivariate logistic regression showed that old age, absence of bacillus Calmette-Guérin (BCG) scar, presence of donor-specific antibody, and KTR group were independent factors for positive LTBI. For participants with initial negative QFT, positive QFT conversion within a 2-year follow-up was higher after kidney transplantation (20%) than in KTCs (5.5%) (P = .034). CONCLUSIONS: This study is the first cohort to follow up LTBI status in patients with kidney transplantation and shows its higher prevalence and incidence in KTRs. It indicates that surveillance of LTBI after renal transplantation is important. In addition to status of kidney transplantation, old age, no BCG vaccination, and positive donor-specific antibody are also positive predictors for LTBI.

Fourth-Generation QuantiFERON-TB Gold Plus: What Is the Evidence?

QuantiFERON-TB Gold Plus (QFT-Plus) is the latest generation of interferon gamma release assays (IGRAs) to receive approval from the U.S. FDA, replacing its predecessor, QuantiFERON-TB Gold In-Tube (QFT-GIT). The novelty of QFT-Plus is that it elicits a response from CD8 T cells, in addition to CD4 T cells, thus collecting a broader response from T-cell subsets than QFT-GIT. It was developed with the aim to improve the detection of latent tuberculosis infection (LTBI), especially among recently exposed contacts, immunocompromised hosts, and young children. In this minireview, we summarize the performance of QFT-Plus compared with that of QFT-GIT among active tuberculosis (TB) patients (a surrogate for LTBI patients), high-risk populations, and low-risk individuals based on recent publications. Studies comparing QFT-Plus to QFT-GIT currently do not support the superior performance of QFT-Plus in individuals with active TB and LTBI. The difference in sensitivity between QFT-Plus and QFT-GIT in active TB patients was not significant in nearly all studies and ranged from -4.0 to 2.0%. Among high-risk groups, the agreement between QFT-Plus and QFT-GIT was 89.9 to 96.0% (kappa coefficient range, 0.80 to 0.91). The specificity in the low-risk population was slightly lower for QFT-Plus than for QFT-GIT, with the difference ranging from -7.4 to 0%. Further studies are needed to accurately evaluate the sensitivity of QFT-Plus in immunocompromised hosts and children. In addition, further evidence is required to validate a modified interpretation of QFT-Plus for the identification of false-positive results in low-risk health care workers.

Treatment of latent tuberculosis infection with short-course regimens in potential living kidney donors.

BACKGROUND: Treatment data for latent tuberculosis infection (LTBI) among potential living kidney donors are scarce. METHODS: This retrospective study was performed to evaluate the prevalence of positive QuantiFERON-TB Gold In-Tube (QFT-GIT) among potential living kidney donors that were screened from 2009 to 2017. We investigated if there was any difference in the time to donation between QFT-GIT-positive and QFT-GIT-negative donors. We assessed the regimens used to treat LTBI and whether the recipients of QFT-GIT-positive donors developed active tuberculosis (TB). RESULTS: Forty out of 427 (9%) potential living kidney donors had a positive QFT-GIT. QFT-GIT-positive donors were as likely as negative donors to undergo donation (30 [75%] vs 315 [81%], P = .33). The time from QFT-GIT testing to donation was longer among QFT-GIT-positive donors (median 221 days [range: 4-1139] vs 86 days [range: 3-1887], P = .001). Twelve-week rifapentine (RPT)/Isoniazid (INH) was the most common treatment used and was not associated with significant adverse reactions. There was a trend toward longer time to donation among QFT-GIT-positive donors who were treated for LTBI compared with QFT-GIT-positive donors who were not (252 days [range: 88-1139] vs 95 days [range: 4-802], P = .05). Twenty-nine recipients of QFT-GIT-positive living kidney donors were evaluated. Eleven of these recipients received kidneys from donors that were not treated for LTBI. Two of these recipients were treated with INH post-transplantation. CONCLUSIONS: The time from QFT-GIT testing to donation was longer among QFT-GIT-positive donors. The short-course regimens appear to be excellent options for LTBI treatment among living kidney donors and avoid delaying organ donation further.

Performance Evaluation of a New Automated Chemiluminescent Immunoanalyzer-Based Interferon-Gamma Releasing Assay AdvanSure I3 in Comparison With the QuantiFERON-TB Gold In-Tube Assay.

BACKGROUND: The interferon-gamma (IFN-γ) releasing assay (IGRA) is widely used for latent tuberculosis infection (LTBI) diagnosis. We evaluated the analytical performance of a new automated chemiluminescent immunoanalyzer-based IGRA (CLIA-IGRA), AdvanSure I3 (LG Life Sciences, Seoul, Korea) and compared it with that of the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay. METHODS: Repeatability and reproducibility were evaluated at four levels. Detection capability, including limit of blank (LoB), limit of detection (LoD), and limit of quantification (LoQ), was evaluated using IFN-γ standard material (National Institute for Biological Standards and Control code: 87/586). Agreement between the results of two assays was evaluated using 341 blood samples from healthcare workers and patients at a tertiary care hospital. To determine the cut-off value of CLIA-IGRA for diagnosing LTBI, the ROC curve was analyzed. RESULTS: Repeatability and reproducibility were 4.86-7.00% and 6.36-7.88% CV, respectively. LoB, LoD, and LoQ were 0.022, 0.077, and 0.249 IU/mL, respectively. IFN-γ values between CLIA-IGRA and QFT-GIT showed a strong correlation within the analytical measurable range of both assays, especially when the value was low. Qualitative comparison of the two assays yielded a 99.1% overall agreement (kappa coefficient=0.98). A cut-off value of 0.35 IU/mL was appropriate for diagnosing LTBI. CONCLUSIONS: CLIA-IGRA is a reliable assay for LTBI diagnosis, with performance similar to that of QFT-GIT.

Preventive tuberculosis treatment effect on QuantiFERON TB-Gold in-tube testing in a high tuberculosis-endemic country: A clinical trial.

BACKGROUND: Whether T-cell interferon-γ responses to Mycobacterium tuberculosis-specific antigens can be influenced by tuberculosis preventive treatment in a high-endemic country is uncertain. METHODS: In this prospective, open-label, controlled study, 513 individuals with silicosis were randomly selected for TB preventive treatment with rifapentine and isoniazid or for observation. QuantiFERON-TB Gold in-tube (QFT-GIT) assay was used to measure IFN-γ response to M. tuberculosis antigens at baseline (T0) and at 6 (T1) and 33 (T2) months after completion of therapy. RESULTS: A total of 220 subjects were included in the final analysis: 105 and 115 in the prevention and observation arms, respectively. The proportions of QFT-GIT reversion from baseline to T1 were similar in the prevention and observation arms (18.4% vs 12.8%, P=0.566). However, reversion from baseline to T2 was more frequent in the prevention arm than in the observation arm, but the difference was not significant (24.2% vs 6.3%, P=0.881). No significant difference was observed in the quantitative responses of QFT-GIT between the two arms during follow-up at T1 (P=0.648) and T2 (P=0.918). CONCLUSIONS: Preventive tuberculosis treatment has no effect on interferon-γ responses measured by serial QFT-GIT assays in a high tuberculosis-endemic country. CLINICAL TRIALS REGISTRATION: http://www.clinicaltrials.gov NCT02430259.

Clinical application of QuantiFERON-TB Gold in-tube in the diagnosis and treatment of tuberculosis.

At present, although it has made great progress in the diagnosis and treatment of tuberculosis, tuberculosis is still an important cause of morbidity and mortality. There were approximately 8.6 million new cases of tuberculosis in 2012, and approximately 1.3 million people died from tuberculosis. Early diagnosis and timely treatment are essential for controlling the spread of tuberculosis infection and reducing mortality. Conventional methods of Mycobacterium tuberculosis detection such as acid-fast staining microscopy and tuberculin skin test are widely used, but with low sensitivity or specificity. In recent years, a newly developed quantitative test, γ-interferon release test (IGRA), has been recognized and widely applied to the early diagnosis and monitoring of tuberculosis. QuantiFERON-TB Gold in-tube (QFT-GIT) is one of the mature IGRA methods. This paper summarizes the researches on QFT-GIT in recent years and introduces its principles, methodology, clinical application, and factors of uncertain results for the diagnosis and treatment of tuberculosis.

Evaluation of QuantiFERON tuberculosis Gold In-Tube assay for diagnosis of active tuberculosis in children.

AIM: Tuberculin skin test (TST) is still used in diagnostic algorithms of childhood tuberculosis (TB). QuantiFERON TB Gold In-Tube assay (QFT-GIT) is an alternative test to TST based on the detection of interferon-gamma release upon in vitro induction of peripheral mononuclear cells by TB antigens. In this study, we aimed to determine the diagnostic value and performance of QFT-GIT for active childhood TB. METHODS: This retrospective study was conducted between January 2005 and December 2011 in three referral hospitals in Turkey with 124 children who were diagnosed with definite active TB. Sensitivity values of TST and QFT-GIT were determined by accepting the microbiological confirmation as the gold standard of diagnosis of TB. RESULTS: In our study, sensitivity of QFT-GIT and TST was found to be 65 and 66% respectively. However, combined usage of QFT-GIT and TST was found to be more sensitive (85%) than TST or QFT-GIT alone (P < 0.0001). Although negative results of QFT-GIT or TST did not exclude the diagnosis of active TB in children, their positivity supported the diagnosis. Specificity could not be measured as only microbiologically confirmed cases of Mycobacterium tuberculosis disease were enrolled in the study. CONCLUSION: Although sensitivities of TST and QFT-GIT are too low to exclude active TB, their positivity supports diagnosis of active TB in children concomitant with signs and symptoms. QFT-GIT and TST should be used together to enhance diagnostic sensitivity and could help exclude a diagnosis of TB if the pretest probability is low.

Performance Evaluation of a New Automated Chemiluminescent Immunoanalyzer-Based Interferon-Gamma Releasing Assay AdvanSure I3 in Comparison With the QuantiFERON-TB Gold In-Tube Assay

BACKGROUND: The interferon-gamma (IFN-γ) releasing assay (IGRA) is widely used for latent tuberculosis infection (LTBI) diagnosis. We evaluated the analytical performance of a new automated chemiluminescent immunoanalyzer-based IGRA (CLIA-IGRA), AdvanSure I3 (LG Life Sciences, Seoul, Korea) and compared it with that of the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay. METHODS: Repeatability and reproducibility were evaluated at four levels. Detection capability, including limit of blank (LoB), limit of detection (LoD), and limit of quantification (LoQ), was evaluated using IFN-γ standard material (National Institute for Biological Standards and Control code: 87/586). Agreement between the results of two assays was evaluated using 341 blood samples from healthcare workers and patients at a tertiary care hospital. To determine the cut-off value of CLIA-IGRA for diagnosing LTBI, the ROC curve was analyzed. RESULTS: Repeatability and reproducibility were 4.86–7.00% and 6.36–7.88% CV, respectively. LoB, LoD, and LoQ were 0.022, 0.077, and 0.249 IU/mL, respectively. IFN-γ values between CLIA-IGRA and QFT-GIT showed a strong correlation within the analytical measurable range of both assays, especially when the value was low. Qualitative comparison of the two assays yielded a 99.1% overall agreement (kappa coefficient=0.98). A cut-off value of 0.35 IU/mL was appropriate for diagnosing LTBI. CONCLUSIONS: CLIA-IGRA is a reliable assay for LTBI diagnosis, with performance similar to that of QFT-GIT.

Performance and correlation of QuantiFERON-TB Gold, T-SPOT.TB and tuberculin skin test in young children with tuberculosis exposure or tuberculosis disease

To evaluate the performance of interferon gamma release assays and tuberculin skin test in Bacillus Calmette-Guerin vaccinated young children. Methods: A cross-sectional study was conducted in healthy children younger than 5 years who were recently diagnosed with tuberculosis or had recent exposure to active tuberculosis. QuantiFERON-TB Gold, T-SPOT.TB and tuberculin skin test were performed in each patient. Results: Of the 60 children, median age 3.3 years, 17 had tuberculosis and 43 had recent tuberculosis exposure. Overall, 15 (25.0%) children had tuberculin skin test reaction =10 mm; 8 (13.3%) were positive by QuantiFERON-TB Gold In-Tube test, and 12 (20.0%) by T-SPOT.TB. Nineteen (31.7%) children had at least one positive test. There was a moderate agreement between interferon gamma release assays and tuberculin skin test. Conclusions: The positive rates of interferon gamma release assays and tuberculin skin test were low in young children who were infected with tuberculosis, supporting the management strategy of not testing children younger than 5 years. (IGRA) do not react to BCG and most NTM[2], are preferred to TST in older children and adults[3], but may be less reactive in young children with immature T-cell function. Due to the limited knowledge of IGRA in BCG-vaccinated young children, we evaluated the performance and correlation of IGRA tests and TST in young children in a high TB burden setting who received BCG vaccination at birth and recently diagnosed with LTBI, or with active TB.