QuantiFERON-TB Gold In-Tube Research Articles

Evaluation of the Diagnostic Efficacy of EC-Test for Latent Tuberculosis Infection in Ambulatory People Living with HIV.

Latent tuberculosis infection (LTBI) co-infected with human immunodeficiency virus (HIV) is more likely to develop into active tuberculosis (ATB), recombinant Mycobacterium tuberculosis fusion protein (ESAT6/CFP10, EC) Test is a latest developed method for LTBI. Compared with the interferon γ release test assays (IGRAs), the diagnostic performance of EC-Test to LTBI screening in HIV needs to be evaluated. A population-based multicenter prospective study was conducted in Guangxi Province, China. The baseline data was collected and LTBI were measured by QuantiFERON-TB Gold In-Tube (QFT-GIT), EC-Test and T-cell spot of the TB assay (T-SPOT.TB). A total of 1478 patients were enrolled. when taking T-SPOT.TB as reference, the value of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and consistency that EC-Test to diagnosis LTBI in HIV is 40.42%, 97.98%, 85.26%, 85.04% and 85.06% respectively; when taking QFT-GIT as reference, the value is 36.00%, 92.57%, 55.10%, 85.09% and 81.13%, respectively. When the CD4+ <200 /μl, the accuracy of EC-Test to T-SPOT.TB and QFT-GIT were 87.12% and 88.89%, respectively; when the 200 ≤ CD4+ ≤ 500 /μl, the accuracy of EC-Test were 86.20% and 83.18%, respectively; when the CD4+ >500/μl, the accuracy of EC-Test were 84.29% and 77.94%, respectively. The incidence of adverse reactions in EC-Test is 34.23% and the serious adverse reactions is 1.15%. EC-Test has good consistency compared with IGRAs in detecting LTBI in HIV no matter in different immunosuppression status or different regions, and the safety of EC-Test is also well, suitable for LTBI screening in HIV in high prevalence settings.

Evaluation of ESAT6-CFP10 Skin Test for Mycobacterium tuberculosis Infection among Persons Living with HIV in China.

Recent global guidelines recommend Mycobacterium tuberculosis antigen-based skin tests, such as the ESAT6-CFP10 (EC) skin test, as acceptable alternatives to the tuberculin skin test (TST) and the QuantiFERON-TB Gold In-Tube test (QFT). However, the diagnostic value of these tests among persons living with HIV (PLHIV) is unknown. We aimed to assess the diagnostic accuracy of the EC among a cohort of PLHIV in China. We recruited PLHIV in Jiangsu Province, China, to assess sensitivity and specificity of the EC test. Participants were tested with the QFT, TST, and EC skin test. Results were stratified by age, M. tuberculosis BCG vaccination, and CD4 count. The sensitivity and specificity of the EC skin test was assessed using distinct cutoffs of the QFT and TST. Of 350 PLHIV enrolled in the study, 58 (16.6%), 89 (25.4%), and 59 (16.9%) tested positive with the EC test, the QFT, and the TST, respectively. Positivity increased with CD4 count; however, these trends were similar across tests. At a 5-mm cutoff, EC skin test specificity was high (99.6%, 95% confidence interval [CI] 95% CI = 97.7 to 100.0); however, sensitivity was moderate (81.4%; 95% CI = 66.6 to 91.6). After stratifying by BCG, the sensitivity and specificity were 86.4% (95% CI = 65.1 to 97.1) and 99.1% (95% CI = 95.0 to 100.0) among vaccinated PLHIV and 76.2% (95% CI = 52.8 to 91.8) and 100.0% (95% CI = 97.2 to 100.0) among unvaccinated PLHIV, respectively. Among PLHIV, the diagnostic value of the EC skin test remained high, regardless of BCG vaccination or CD4 count. The EC skin test performed comparably to TST and may be a valid alternative diagnostic test to use in settings or populations with high HIV prevalence and BCG vaccination. To our knowledge, this is the first study to evaluate the novel ESAT6-CFP10 skin test among PLHIV. Among 350 PLHIV, the test displayed high specificity and sensitivity, a finding which did not markedly differ based on BCG vaccination and CD4 count.

Positive rate and risk factors of latent tuberculosis infection among persons living with HIV in Jiangsu Province, China.

To analyze the latent tuberculosis infection (LTBI) among persons living with HIV(PLWH) in Jiangsu Province, to explore the factors affecting the positive rate of LTBI, and to take appropriate measures to control tuberculosis (TB) infection. A cross-sectional study was conducted among PLWH in Jiangsu Province from June to July 2021. All PLWH in Jiangsu Province were used as the study population. Currently, the diagnosis of LTBI lacks a "gold standard" and can only be assisted by the immunological method. In this study, Tuberculin skin test (TST), ESAT6-CFP10 test (EC), and QuantiFERON-TB gold in-tube (QFT) were used to detect the positive rate of LTBI among PLWH and to analyze their risk factors. A total of 340 prisoners were included, 89.7% were male, the median age was 38 years [Interquartile Range (IQR):32-46 years], these patients were on Antiviral Therapy (ART), and median CD4 counts was 376 (IQR: 261-496), 103 (30.3%) were positive in at least one test, LTBI by TST was 16.5%, LTBI by EC was 15.9%, LTBI by QFT was 26.2%. Univariate analysis showed the results for TST, EC, and QFT were not affected by CD4 counts (p>0.05), and multivariate analysis showed that a history of incarceration was associated with an increased risk of positive TST (adjusted odds ratio [aOR]=1.98;95% CI,1.03-3.82), EC (aOR=2.65;95% CI,1.37-5.12) and QFT (aOR=2.01;95%CI,1.12-3.57), in addition, female gender was associated with increased risk of positive TST (aOR=3.66;95%CI,1.60-8.37) and EC (aOR=3.43;95%CI,1.46-8.07), and contact history of TB patients was associated with increased risk of TST (aOR= 2.54;95%CI,1.23-5.22) and QFT (aOR=2.03;95%CI,1.03-3.99), and ethnic minorities (aOR=0.26;95%CI,0.12-0.57), longer duration of incarceration was associated with an increased risk of positive QFT (aOR=1.12;95%CI,1.02-1.24). Conclusions Female gender, and ethnic minorities, history of incarceration, longer duration of incarceration, and contact history of TB patients are risk factors for LTBI among PLWH in Jiangsu Province, and attention should be paid to TB control in this population.

Risk of tuberculosis transmission by children in Hamburg, Germany

BackgroundData from a prospective molecular-epidemiologic study (1997–2021) in Hamburg, Germany, were evaluated to assess the transmission risk of Mycobacterium tuberculosis complex (Mtbc) by children <15 years in a low-incidence setting. MethodsIsolates of Mtbc were genotyped whole genome sequencing, applying a core genome multilocus sequence typing scheme. Close contacts of culture-confirmed children were examined for latent Mtbc infections (LTBI) with particular focus on IGRA testing. ResultsOut of 3154 culture-confirmed tuberculosis (TB) cases, 79 (2.5%) were children <15 years. Of those, 52 (58%) had pulmonary TB. Genotyping revealed that 35 of the 52 children (67%) were epidemiologically confirmed secondary cluster members; all of their source cases were adults. Six immigrant children presented without a presumed source case; their TB diagnoses came on average 48 weeks (interquartile range [IQR] 71) after their arrival in Germany. Three German-born children were determined to have been infected by adult relatives while visiting their parents' home country. Of the 317 children's close contacts tested with QuantiFERON-TB Gold-In Tube for LTBI, only 21 (6.6%) were positive. Absent a history of prior exposure or immigration from a high-incidence country, none of the contacts of younger (<10 years) TB-afflicted children was latently infected, whereas 2 older children infected 12 of their contacts, children and adults. During a mean observational period of 551 weeks (IQR 735) on average, no secondary TB cases appeared. ConclusionsChildren with pulmonary TB disease, especially those aged below 10 years, rarely transmit Mtbc to their close contacts in a low-incidence setting.

Comparing the diagnostic performance of QuantiFERON-TB Gold Plus with QFT-GIT, T-SPOT.TB and TST: a systematic review and meta-analysis

BackgroundQuantiFERON-TB Gold Plus (QFT-Plus) is an important test that has emerged in recent years for detecting TB infection. We conducted a review to compare the sensitivity, specificity and positive rate of QFT-Plus with that of QuantiFERON-TB Gold In-Tube (QFT-GIT), T-cell spot of tuberculosis assay (T-SPOT.TB) and Tuberculin test (TST).MethodsPubMed and Embase were searched, without language restrictions, from 1 January 2015 to 31 March 2022 using “Mycobacterium tuberculosis Infections” and “QuantiFERON-TB-Plus” as search phrases. We estimated the sensitivity from studies of patients with active tuberculosis, specificity from studies of populations with very low risk of TB exposure, and positive rate from studies of high-risk populations. The methodological quality of the eligible studies was assessed, and a random-effects model meta-analysis was used to determine the risk difference (RD). We assessed the pooled rate by using a random-effects model. This study was registered in PROSPERO (CRD 42021267432).ResultsOf 3996 studies, 83 were eligible for full-text screening and 41 were included in the meta-analysis. In patients with active TB, the sensitivity of QFT-Plus was compared to that of QFT-GIT and T-SPOT.TB, respectively, and no statistically differences were found. In populations with a very low risk of TB exposure, the specificity of QFT-Plus was compared with that of QFT-GTI and T-SPOT.TB, respectively, and no statistically differences were found. Two studies were eligible to compare the specificity of the QFT-Plus test with that of the TST test, and the pooled RD was 0.12 (95% CI 0.02 to 0.22). In high-risk populations, 18 studies were eligible to compare the positive rate of the QFT-Plus test with that of the QFT-GIT test, and the pooled RD was 0.02 (95% CI 0.01 to 0.03). The positive rate of QFT-Plus was compared with that of T-SPOT.TB and TST groups, and no statistically differences were found.ConclusionsThe diagnostic performance of QFT-Plus was similar to that of QFT-GIT and T-SPOT.TB, but was slightly more specific than TST.

The association between diabetes status and latent-TB IGRA levels from a cross-sectional study in eastern China.

There is a debate regarding the sensitivity of the QuantiFERON-TB Gold In-Tube (QFT) among people with diabetes, and prior studies have shown heterogeneous results. We evaluated whether the QFT TB antigen was modified among persons with differing diabetes status and other related risk factors. A cross-sectional study of 5,302 people was conducted to screen latent tuberculosis infection (LTBI) in eastern China. The QFT assay was performed as an indicator of LTBI. Fasting plasma glucose (FPG) was collected from each participant; the definition of diabetes followed the guidelines from the American Diabetes Association. Participants were classified into normoglycemia, prediabetes, undiagnosed diabetes, and previously diagnosed diabetes to evaluate the relationship between the QFT TB antigen and distinct diabetes status. TB antigen values from the QFT were statistically different among participants with differing diabetes status (P = 0.008). Persons with undiagnosed diabetes had a higher TB antigen value (0.96 ± 0.20) than persons with normoglycemia (0.50 ± 0.02, P < 0.05). However, the TB antigen values demonstrated no significant difference among the four different diabetic groups when stratified by the standard cutoff for the QFT (P = 0.492 for the positive group and P = 0.368 for the negative group). In a linear regression model, we found that FPG, age, and smoking were positively associated with the QFT TB antigen value (P = 0.017, P < 0.001, and P < 0.001). Diabetes status had little influence on the level of QFT TB antigen response among IGRA-positive persons. However, FPG, old age, and smoking were important risk factors for increasing levels of QFT TB antigen.

Gut microbiota composition can reflect immune responses of latent tuberculosis infection in patients with poorly controlled diabetes

BackgroundDiabetes mellitus (DM) is a major risk factor for tuberculosis (TB). Evidence has linked the DM-related dysbiosis of gut microbiota to modifiable host immunity to Mycobacterium tuberculosis infection. However, the crosslinks between gut microbiota composition and immunological effects on the development of latent TB infection (LTBI) in DM patients remain uncertain.MethodsWe prospectively obtained stool, blood samples, and medical records from 130 patients with poorly-controlled DM (pDM), defined as ever having an HbA1c > 9.0% within previous 1 year. Among them, 43 had LTBI, as determined by QuantiFERON-TB Gold in-Tube assay. The differences in the taxonomic diversity of gut microbiota between LTBI and non-LTBI groups were investigated using 16S ribosomal RNA sequencing, and a predictive algorithm was established using a random forest model. Serum cytokine levels were measured to determine their correlations with gut microbiota.ResultsCompared with non-LTBI group, the microbiota in LTBI group displayed a similar alpha-diversity but different beta-diversity, featuring decrease of Prevotella_9, Streptococcus, and Actinomyces and increase of Bacteroides, Alistipes, and Blautia at the genus level. The accuracy was 0.872 for the LTBI prediction model using the aforementioned 6 microbiome-based biomarkers. Compared with the non-LTBI group, the LTBI group had a significantly lower serum levels of IL-17F (p = 0.025) and TNF-α (p = 0.038), which were correlated with the abundance of the aforementioned 6 taxa.ConclusionsThe study results suggest that gut microbiome composition maybe associated with host immunity relevant to TB status, and gut microbial signature might be helpful for the diagnosis of LTBI.

QuantiFERON-TB Gold Plus and QuantiFERON-TB Gold In-tube assays for detecting latent tuberculosis infection in Thai healthcare workers.

Detecting latent tuberculosis infection (LTBI) is important, especially in high-risk populations including healthcare workers (HCWs). QuantiFERON-TB Gold Plus (QFT-Plus) is a new version of the interferon-gamma release assays (IGRAs) to replace the QuantiFERON-TB Gold In-tube (QFT-GIT). However, data on the use of QFT-Plus for LTBI detection in high TB-burden countries are limited. This study was conducted in a TB-endemic setting in Thailand. HCWs were enrolled in the study and underwent both tests during the annual health screening. The testing results were compared and the concordance was determined. Of 102 HCWs, 11 (10.78%) were positive according to both tests, and 15 (14.71%) were positive according to QFT-Plus. The overall agreement between assays was 96.08%, with Cohen's kappa coefficient (k) at 0.82. All four discordant results occurred with QFT-GIT negative and QFT-Plus positive. The comparison between QFT-GIT and QFT-Plus based on each antigen tube (TB1 or TB2) exhibited similar concordance with 99.02% and 95.10% agreement, respectively. The intra-comparison between TB1 and TB2 of QFT-Plus also showed good concordance at 96.08%. Among this group of HCWs, the LTBI prevalence of any positive results in both tests was low. Overall, the study showed good agreement between QFT-Plus and QFT-GIT (k = 0.82) with a minimal difference, suggesting similar assay performance to that mainly carried out in TB-low incidence countries. The results support the use of QFT-Plus for detecting LTBI in a format similar to QFT-GIT.

The exhaustion of lymphocytes is the main factor that decreases the sensitivity of QFT-GIT detection in silicosis

BackgroundTuberculosis infection is a major complication of silicosis, but there is no study on whether silicosis can affect the sensitivity of QuantiFERON-TB Gold In-Tube (QFT-GIT) assays. This study will analyze the relationship between silicosis and QFT-GIT, determine the main factor of the QFT-GIT sensitivity decrease in silicosis and explore the methods to increase the sensitivity.MethodsSilicosis patients with positive tubercle bacillus cultures were collected. The QFT-GIT, flow cytometry and blocking antibodies were used.ResultsThe sensitivity of QFT-GIT in silicosis patients (58.46%) was significantly decreased and the expression of PD-1 on T cells and CD56+NK cells in pulmonary tuberculosis combined with silicosis were higher than normal tuberculosis patients and silicosis only patients. Further analysis found that the ratio of PD-1+CD4+T and IFN-γwere negatively correlated and blockaded the PD-1 pathway with antibodies can restore the sensitivity of QFT-GIT in silicosis.ConclusionsThis is the first study to analyze the relationship between immune exhaustion and QFT-GIT in silicosis and found that the sensitivity of QFT-GIT was decreased by the expression of PD-1 on lymphocytes. Antibody blocking experiments increased the expression of IFN-γ and provided a new method to improve the sensitivity of QFT in silicosis. The study also found that silicosis can increase PD-1 expression. As PD-1 functions in infectious diseases, it will promote immune exhaustion in silicosis and lead to tuberculosis from latent to active infection. The study provided theoretical evidence for the diagnosis and immunotherapy of silicosis complications, and it has great value in clinical diagnostics and treatment.

Predictors for False-Negative Interferon-Gamma Release Assay Results in Hemodialysis Patients with Latent Tuberculosis Infection.

The present study aimed to clinically evaluate the effect of T-cell dysfunction in hemodialysis (HD) patients with latent tuberculosis (TB) infection (LTBI) who were false-negatives in the QuantiFERON-TB Gold In-Tube (QFT-GIT) test. Whole blood samples from a total of 20 active TB patients, 83 HD patients, and 52 healthy individuals were collected, and the QFT-GIT test was used for measuring Mycobacterium tuberculosis (MTB)-specific interferon gamma (IFN-γ) level. The positive rate of the IFN-γ release assays (IGRAs) in HD patients was lower than the negative rate. The mean value of MTB-specific IFN-γ level, which determines the positive rate of the IGRA test, was highest in active TB, followed by HD patients and healthy individuals. Among HD patients, phytohemagglutinin A (PHA)-stimulated IFN-γ levels of approximately 40% were 10.00 IU/mL or less. However, there was no low level of PHA-stimulated IFN-γ in the healthy individuals. This reveals that T-cell function in HD patients was reduced compared to healthy individuals, which leads to the possibility that QFT-GIT results in HD patients are false-negative. The clinical manifestations of TB in patients on HD are quite non-specific, making timely diagnosis difficult and delaying the initiation of curative treatment, delay being a major determinant of outcome.

Determinants of latent tuberculosis infection and treatment interruption in long-term care facilities: A retrospective cohort study in Taiwan.

Latent tuberculosis infection (LTBI) treatment is challenging in long-term care facilities (LTCFs) residents due to the occurrence of medical complexities. However, factors associated with treatment interruption have not been extensively studied. This retrospective cohort study aimed to determine LTBI-associated factors and treatment interruption in LTCF residents and employees in Taiwan. From May 2017 through September 2020, the residents and employees of 20 LTCFs in Taipei, Taiwan, were screened for LTBI by using QuantiFERON-TB Gold In-Tube test. The LTBI individuals underwent directly observed preventive therapy (DOPT), including regimens of 9-month daily isoniazid (9H) and 3-month weekly isoniazid plus rifapentine (3HP). All the LTBI cases were followed up till treatment completion, death, or treatment interruption. Among 2207 LTCF subjects, 16.8% had LTBI. After controlling for other covariates, residents of public facilities had a significantly higher LTBI prevalence than those of private facilities (adjusted odds ratio [AOR]=1.43; 95% confidence interval [CI]: 1.08-1.88). Among 264 LTBI cases receiving preventive therapy, 52 (19.7%) had treatment interruption. LTBI cases receiving 3HP were less likely to have treatment interruption than those receiving 9H (AOR=0.22; 95% CI: 0.07-0.71). LTCF residents, particular those living in public facilities, had a high LTBI prevalence. 3HP with DOPT is considered the priority regimen for preventive therapy among LTBI cases in LTCFs.

Monocyte-to-lymphocyte ratio is significantly associated with positive QuantiFERON-TB Gold-In-Tube and adult survival: an observational study

This study aimed to find significant factors associated with tuberculosis (TB) infection and disease development. The participants were from National Health and Nutrition Examination Survey (NHANES) and National Death Index (NDI). The tuberculosis infection was defined as a positive QuantiFERON-TB Gold-In-Tube (QFT-GIT). The Least Absolute Shrinkage and Selection Operator (LASSO) model was used to screen variables associated with QFT-GIT among 23 laboratory measures. Then the logistic regression analyses were performed to assess the independent factors, followed by a comprehensive nomogram model construction. Receiver operating characteristic (ROC) and Decision Curve (DCA) analyses were used to assess the performance of comprehensive model on QFT-GIT result and death risk. Of 5256 individuals included, 521 individuals had positive QFT-GIT. LASSO analysis indicated that 11 variables were associated with QFT-GIT result, and logistic regression analyses further found sodium and monocyte-to-lymphocyte ratio (MLR) were independent factors. After adjusting for potential confounders, the correlation of sodium and MLR with QFT-GIT result was still observed. The comprehensive model based on sodium, MLR, and important clinical characteristics can predict 0.8 probability of positive QFT-GIT and achieve more clinical net benefit. ROC analysis by training and validation sets showed the favorable prediction performance. Comprehensive model also presented favorable performance in evaluating the death risk of individuals with positive QFT-GIT. We also found MLR rather than sodium was independently related to the death risk. Both MLR itself and comprehensive model were all significantly related to the positive QFT-GIT and death risk, which might participate in the initiation and progression of tuberculosis infection.

Host, technical, and environmental factors affecting QuantiFERON-TB Gold In-Tube performance in children below 5 years of age

Interferon-gamma release assays performance can be impaired by host-related, technical and environmental factors, but data in young children are limited. We performed a cross-sectional study of children < 5 years-of-age at risk of tuberculosis (TB), using QuantiFERON-TB Gold In-Tube (QFT-GIT) assays. The impact of the following was evaluated: (i) host-related [age; hematological parameters; erythrocyte sedimentation rate (ESR); C-reactive protein (CRP); and tobacco smoke exposure (TSE) based on serum cotinine concentrations], (ii) technical (pre-analytical delay) and (iii) environmental factors (annual season; monthly temperatures). Of 204 children, 35 (17.2%) were diagnosed with latent TB infection or TB disease. QFT-GIT results were indeterminate in 14 (6.9%) patients. In multivariate analysis, younger age and higher ESR were associated with lower positive control responses (beta: 0.247, p = 0.002 and − 0.204, p = 0.007, respectively), and increasing age was associated with lower rates of indeterminate QFT-GIT results [OR (95% CI) 0.948 (0.903–0.996) per month, p = 0.035]. In children with positive QFT-GIT results, average monthly temperatures correlated with antigen responses (r = 0.453, p = 0.020); also, antigen responses were lower in winter than in other seasons (p = 0.027). Serum cotinine concentrations determined in a subgroup of patients (n = 41) indicated TSE in 36 (88%), positive control responses being lower in children with TSE (p = 0.034). In children < 5 years-of-age, young age, elevated ESR, temperature, annual season and TSE can affect the performance of QFT-GIT assays.

Tuberculin skin test versus QuantiFERON-TB gold in-tube for latent tuberculosis screening in people living with HIV in a resource-limited setting.

To compare QuantiFERON-TB Gold-in-Tube (QFT) and tuberculin skin test (TST) in the diagnosis of latent tuberculosis infection (LTBI) among people living with HIV (PLWHIV). A cross-sectional study was carried out between 2017-2018. Tuberculin skin test and QFT were performed and their concordance was measured. The gold standard for LTBI was defined as positivity to any of the tests. A logistic regression model was carried out to predict the QFT result in patients with a negative TST. A total of 510 PLWHIV were included, with 409 (80.2%) being male. The mean age of the patients was 41.3 ± 11.8years. The median time since HIV diagnosis was 5years (IQR 2-10), with a median CD4+ count of 541 (IQR 340-757) cells/mm3. Overall, 20 patients had an isolated TST+, 22 an isolated QFT+ and 15 had both positive. Concordance between tests showed a kappa coefficient of .37. Overcrowding was the only predictor for a positive QFT after a negative TST (p = .003). There was fair agreement between tests in PLWHIV. In conditions of limited access to QTF, a TST-based strategy could be considered, with sequential use of QTF in high-risk patients with a negative result, especially those who live in overcrowded conditions.

Dual latent tuberculosis screening with tuberculin skin tests and QuantiFERON-TB assays before TNF-α inhibitor initiation in children in Spain

Tumor-necrosis-factor-α inhibitors (anti-TNF-α) are associated with an increased risk of tuberculosis (TB) disease, primarily due to reactivation of latent TB infection (LTBI). We assessed the performance of parallel LTBI screening with tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube assays (QFT-GIT) before anti-TNF-α treatment in children with immune-mediated inflammatory disorders in a low TB-burden setting. We conducted a multicenter cohort study involving 17 pediatric tertiary centers in Spain. LTBI was defined as the presence of a positive TST and/or QFT-GIT result without clinical or radiological signs of TB disease. A total of 270 patients (median age:11.0 years) were included, mainly with rheumatological (55.9%) or inflammatory bowel disease (34.8%). Twelve patients (4.4%) were diagnosed with TB infection at screening (LTBI, n = 11; TB disease, n = 1). Concordance between TST and QFT-GIT results was moderate (TST+/QFT-GIT+, n = 4; TST−/QFT-GIT+, n = 3; TST+/QFT-GIT-, n = 5; kappa coefficient: 0.48, 95% CI: 0.36–0.60). Indeterminate QFT-GIT results occurred in 10 patients (3.7%) and were associated with young age and elevated C-reactive protein concentrations. Eleven of 12 patients with TB infection uneventfully completed standard LTBI or TB treatment. During a median follow-up period of 6.4 years, only 2 patients developed TB disease (incidence density: 130 (95% CI: 20–440) per 100,000 person-years), both probable de novo infections.Conclusion: A substantial number of patients were diagnosed with LTBI during screening. The dual strategy identified more cases than either of the tests alone, and test agreement was only moderate. Our data show that in children in a low TB prevalence setting, a dual screening strategy with TST and IGRA before anti-TNF-α treatment is effective.What is Known:• The optimal screening strategy for latent tuberculosis in children with immune-mediated inflammatory disorders remains uncertain.• Children receiving anti-TNF-α drugs are at increased risk of developing severe tuberculosis disease.What is New:• A dual screening strategy, using TST and an IGRA assay, identified more children with latent tuberculosis than either of the tests alone.• Identification and treatment of latent tuberculosis before initiation of anti-TNF-α therapy averted incident tuberculosis cases.

The diagnostic value of an interferon gamma release assay in new cases of active pulmonary tuberculosis and the factors influencing its negative results

ObjectiveThe aim of the study was to investigate the diagnostic value of an interferon gamma release assay (IGRA) - QuantiFERON-TB GOLD in-tube (QFT-GIT) - to identify new cases of active pulmonary tuberculosis (PTB) in Quzhou City, and to assess possible factors associated with false-negative IGRA results in bacteriologically confirmed PTB. MethodsThis study collected clinical data of suspected adult PTB patients who underwent QFT-GIT in Quzhou People's Hospital between January 1, 2020 and December 31, 2020, and calculated the total sensitivity, specificity of QFT-GIT in new case of active PTB patients were 90.9% (401/448) and 72.9%(929/1275), respectively. Univariate and multivariate logistic regression were used to analyze the influencing factors of the false-negative results of QFT-GIT. ResultsA total of 1723 patients were enrolled, including 448(448/1723,26.0%) with new case of active PTB (389 cases were bacteriologically confirmed and 59 cases were clinically diagnosed) and 1275 non-PTB patients. There were 747(747/1723,43.4%) patients with positive results of QFT-GIT, among whom 401 were new case of active PTB patients (347 cases were bacteriologically confirmed and 54 cases were clinically diagnosed) and 346 were non-PTB patients. The total sensitivity and specificity of QFT-GIT in the diagnosis of new case of active PTB patients were 90.9% and 72.8% respectively. In bacteriologically comfirmed PTB patients, multivariate conditional logistic regression analysis showed that BMI and diabetes, malignant tumors and severe infections were all independent risk factors for the false-negative results of QFT-GIT. ConclusionQFT-GIT showed high sensitivity and relatively low specificity in the diagnosis of new case of active PTB patients. In clinical practice, we should analyze the suspected PTB patients comprehensively in terms of whether they are overweight or complicated with diabetes, malignant tumors or severe infections, and avoid missing the diagnosis of PTB.

Selection of the cutoff value of the tuberculin skin test for diagnosing students who need preventive treatment: A school-based cross-sectional study

ObjectiveTuberculosis outbreaks in schools are common in China. This study aimed to introduce and evaluate a new screening process to help control outbreaks.MethodsScreening information of students in three schools with tuberculosis outbreaks was collected. QuantiFERON-TB gold in-tube (QFT) results were used as the reference standard to determine the cutoff value of the tuberculin skin test (TST) for diagnosing students who need to have preventive medication.ResultsA total of 1,232 students and teachers from three different schools that all had more than three student patients with tuberculosis were included in this study. In total, 308 (25.0%) students had an induration diameter ≥10 mm; among students in a class different from the index case, the infection rate was 24.4% (264/1,084), which was lower than the rate among students in the same class (29.7%) (P = 0.157). Students in the same class as the index tuberculosis case had a much higher QFT positivity compared to those in a different class (58.1% vs. 7.7%, P < 0.0001). Diagnostic agreement between TST ≥10 mm and QFT was 36.6%. The diagnostic value reached the highest when the induration diameter of TST was ≥9 mm, with a sensitivity and specificity of 94.1% (95% CI: 89.4%–97.1%) and 27.6% (95% CI: 24.9%–30.4%), respectively. The area under the curve (AUC) was 0.664 (95% CI: 0.637–0.690, P < 0.0001).ConclusionIn tuberculosis outbreaks in schools, if there are three or more cases of students with tuberculosis in a class or if the moderate or strong TST positivity rate is much higher than the normal range in the region, attention should be paid to those with moderately positive TST results. Interferon-gamma release assays (IGRAs) are recommended to be conducted following TST on the day of reading the results, especially among students sharing the same class with the index case. In resource-poor areas lacking IGRAs, the induration diameter of TST can be appropriately reduced from 15 to 9 mm to enhance the sensitivity of TST.

ISOLATED RETINAL VASCULITIS: Prognostic Factors and Expanding the Role of Immunosuppressive Treatment in Retinal Vasculitis Associated With Positive QuantiFERON-TB Gold Test.

To identify prognostic factors for poor visual outcomes in patients with isolated retinal vasculitis and to elucidate the outcome of immunosuppressive treatment without the use of antituberculosis drugs for patients with retinal vasculitis associated with a positive QuantiFERON-TB Gold In-Tube (QFT) test. A retrospective chart review was performed of patients presenting with retinal vasculitis. After the diagnosis of active retinal vasculitis had been confirmed by fluorescein angiography and other possible causes of retinal vasculitis had been excluded, patients were categorized into two groups by their QFT result. Potential associated factors between the poor and good visual outcome groups were statistically analyzed by the chi-square test and logistic regression model with generalized estimating equations. Seventy-three eyes (48 patients) were enrolled in this study. After univariate analysis, multivariate logistic regression analysis was performed and revealed that logMAR visual acuity at the initial visit ( P = 0.01) and outer retinal disruption ( P = 0.03) were the two factors significantly associated with poor visual outcomes. Systemic corticosteroids were administered without the use of antituberculosis drugs to all 16 cases of presumed tuberculous retinal vasculitis associated with positive QFT (26 eyes), 10 (63%) of whom were given nonsteroidal immunosuppressive drugs and achieved inflammatory control and treatment success. Risk factors leading to poor visual outcome in patients with isolated retinal vasculitis have been identified. Immunosuppressive treatment without antituberculosis drugs seems to be a promising regimen for selected patients with presumed tuberculous retinal vasculitis under vigilant care.

Factors Influencing False-Negative Results of QuantiFERON-TB Gold In-Tube (QFT-GIT) in Active Tuberculosis and the Desirability of Resetting Cutoffs for Different Populations: A Retrospective Study.

Objectives The value of QuantiFERON-TB Gold In-Tube (QFT-GIT) in the diagnosis of TB varies by population, comorbidities, and other factors. In this study, we aimed to investigate factors that influence false-negative results of QFT-GIT test in the diagnosis of TB as well as the impact of different cutoffs on the diagnostic value. Methods A total of 3562 patients who underwent QFT-GIT tests at Shanghai Pulmonary Hospital were enrolled retrospectively between May 2016 and May 2017. False-negative and false-positive results were analyzed using different clinical stratifications. The optimal cutoff values were established under different clinical conditions. Results Positive QFT-GIT results greatly shortened the time taken to diagnose smear-negative TB. The factors of age, smear and culture results, site of TB, comorbidity with tumors, white blood cell count, neutrophil count, and CD4/CD8 ratio were significantly correlated with false-negative QFT-GIT results (p < 0.05). Personalized cutoff values were established according to different influencing factors. The results showed high consistency between the smear-negative and total populations. Conclusion QFT-GIT can facilitate the early diagnosis of smear-negative TB. The diagnostic performance of the QFT-GIT test in the diagnosis of active TB was shown to be affected by many clinical factors. Personalized cutoff values may have superior value in the identification of active tuberculosis under different conditions.

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

BackgroundDifferential 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.MethodA 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.ResultsOf 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).ConclusionThe 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.