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Objectives: Systemic vasculitis patients are at a higher risk of developing latent tuberculosis infection (LTBI). However, there is currently no literature elucidating the positivity rate and risk factors for LTBI in systemic vasculitis patients. Methods: Our study is a multi-center, cross-sectional study that enrolled systemic vasculitis patients from 13 comprehensive hospitals in China. T-SPOT.TB as the screening method for LTBI, the study investigated the positivity rate of LTBI in systemic vasculitis patients and the factors associated with T-SPOT.TB results. Results: A total of 191 systemic vasculitis patients were included and the positive rate of T-SPOT.TB was 31.4%. The highest T-SPOT.TB positivity rate was observed in Behçet's syndrome (BD) (72/191, 37.7%). There were statistically significant differences between the LTBI group and non-LTBI group in terms of systemic vasculitis type (P = 0.010), albumin levels (P = 0.034), erythrocyte sedimentation rate (P = 0.016), and corticosteroid dosage (P = 0.047). Multivariate regression analysis revealed that smoking history (aOR = 3.809, 95%CI: 1.341–10.817) and BD (aOR = 2.106, 95%CI: 1.042–4.254) were independent risk factors of T-SPOT.TB postive results, besides decreased lymphocyte count (aOR = 0.114, 95%CI: 0.013–0.973), and high-dose glucocorticoids use (aOR = 0.386, 95%CI: 0.149–1.003) were independent risk factors of T-SPOT.TB negative results. Conclusions: The prevalence of LTBI is high in systemic vasculitis patients, especially those with BD or smoking history. Patients with decreased lymphocyte counts and high-dose glucocorticoid use are more likely to have a negative T-SPOT.TB results. Therefore, LTBI screening should be performed based on the characteristics of the patient during the diagnosis and treatment of systemic vasculitis. Key Points • We explored the positivity rate and risk factors of LTBI in systemic vasculitis patients from 13 hospitals in China. • There were 191 systemic vasculitis patients in our study. The positive rate of T-SPOT.TB was 31.4%. The predominant type of systemic vasculitis was BD, with a T-SPOT.TB positive rate of 44.4%. The second type was TA, with a T-SPOT.TB positive rate of 25.0%. • The prevalence of LTBI is high in systemic vasculitis patients, especially those with Behçet's syndrome or smoking history. Decreased lymphocyte counts and high-dose glucocorticoid use are more likely to have a negative T-SPOT.TB results. • LTBI screening using T-SPOT.TB should be conducted during the diagnosis and treatment of systemic vasculitis. [ABSTRACT FROM AUTHOR]

Objective: This study aims to evaluate the diagnostic accuracy of a Mycobacterium tuberculosis (MTB)-specific triple-color FluoroSpot assay (IFN-γ/IL-2/TNF-α) in the differentiation of tuberculosis (TB) infection status in febrile patients. Method: Febrile patients with suspected active TB (ATB) were consecutively enrolled. The frequencies and proportions of MTB-specific T cells secreting IFN-γ, IL-2, and TNF-α were detected at the single-cell level by triple-color FluoroSpot assay. The diagnostic index was fitted with a binary logistic regression model, and the diagnostic accuracy was evaluated according to the receiver operating characteristic (ROC) curve. The sensitivity, specificity, predictive values (PV), and likelihood ratios (LR) were calculated. Result: A total of 210 febrile patients were enrolled, 53 patients were diagnosed with ATB (28 pathogen-confirmed vs. 25 clinically diagnosed) and 157 patients were non-ATB (84 with latent tuberculosis infection (LTBI) vs. 73 uninfected with MTB). Additionally, 30 pathogen-confirmed ATB patients were assembled. When diagnosing ATB, the area under the ROC curve (AUROC) of the MTB-specific triple-color FluoroSpot assay was significantly better than that of T-SPOT.TB (0.882 vs. 0.811, p = 0.017). With the fitted diagnostic index at a cutoff value of 0.378, the sensitivity, specificity, LR+, and LR- were 74.7%, 93.0%, 10.66, and 0.27, respectively. When differentiating ATB from LTBI, the AUROC of the FluoroSpot assay and T-SPOT.TB was 0.878 and 0.692, respectively (p < 0.001). With a diagnostic index of 0.413, the sensitivity, specificity, LR+, and LR were 77.1%, 85.7%, 5.40, and 0.27, respectively. Conclusion: The MTB-specific triple-color FluoroSpot (IFN-γ/IL-2/TNF-α) might be helpful for the differentiation of TB infection status in febrile patients. [ABSTRACT FROM AUTHOR]

Introduction Identifying tuberculosis infection (TBI) using interferon-gamma release assays (IGRAs) is a primary component of clinical and public health efforts to prevent pediatric tuberculosis (TB). Pediatric data comparing the 2 IGRAs in the United States are very limited. We compared the performance of the 2 IGRAs among a large pediatric cohort tested for TBI and assessed whether discordance might be due to quantitative results close to test cutoff values. Methods Children aged 0-15 years with both T-SPOT. TB (T-SPOT) and QuantiFERON-TB Gold In-Tube (QFT-GIT) tests were identified from a US multicenter study enrolling people at elevated risk of TBI or progression to TB disease. Results were compared using McNemar's Chi-square tests with stratification by age category and testing reason. Percent agreement and kappa statistics were also calculated. We characterized quantitative test results among children with discordant QFT-GIT-positive/T-SPOT-negative results. Results Among 3793 children, a higher number had positive QFT-GIT than T-SPOT (10.1% vs 7.4%, P  < .001). This difference was noted for all age categories except <2 years, and for children with close-contact and non-close contact test indications. Among discordant QFT-GIT-positive/T-SPOT-negative children, lowering the positive threshold for T-SPOT to include borderline spot counts (5-7) did not eliminate the discordance, nor were QFT-GIT antigen-minus-nil results concentrated in the range just above the standard cutoff of 0.35 IU/mL. Conclusions In a large pediatric cohort tested for TBI, QFT-GIT had a higher proportion of positive results than T-SPOT, and discordance was not related to quantitative results close to the established diagnostic cutoffs. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods Results Conclusions Patients with cancer are at elevated risk for tuberculosis (TB) reactivation. Diagnosis of latent TB infection and TB disease remains challenging in this patient population despite the advent of interferon‐γ release assays (IGRA).We retrospectively reviewed medical records of all patients with cancer who had IGRA testing (QuantiFERON–TB [QFT‐TB] or T‐SPOT.TB) at a major cancer center in the United States from June 2010 to July 2017. The results were analyzed with respect to the likelihood of latent TB infection and TB disease.A total of 1299 patients were included with 1599 tests performed: 586 QFT‐TB and 1013 T‐SPOT.TB. Forty‐nine (4%) patients were diagnosed with latent TB, and four (1%) with TB disease. T‐SPOT.TB was more likely to yield an actionable result (positive or negative) than QFT‐TB (89% vs. 65%, p < 0.001). The rate of indeterminate results for QFT‐TB was higher than the rate of invalid results for T‐SPOT.TB (35% and 10%, respectively, p < 0.001). On multivariate analysis, independent predictors of an invalid T‐SPOT.TB included prior receipt of alemtuzumab, lower hemoglobin, absolute lymphocyte count, or serum albumin (p < 0.05 each), whereas the independent predictors of an indeterminate QFT‐TB were female gender, prior receipt of systemic corticosteroids, and lower hemoglobin, or serum albumin or higher absolute neutrophil count (p < 0.05 each).T‐SPOT.TB yielded more actionable results than QFT‐TB in patients with cancer. T‐SPOT.TB might be a better IGRA for screening for latent TB infection in patients with cancer, although a direct comparison would be needed to definitively determine this. [ABSTRACT FROM AUTHOR]

ObjectiveThis study aims to evaluate the diagnostic accuracy of a Mycobacterium tuberculosis (MTB)-specific triple-color FluoroSpot assay (IFN-γ/IL-2/TNF-α) in the differentiation of tuberculosis (TB) infection status in febrile patients.MethodFebrile patients with suspected active TB (ATB) were consecutively enrolled. The frequencies and proportions of MTB-specific T cells secreting IFN-γ, IL-2, and TNF-α were detected at the single-cell level by triple-color FluoroSpot assay. The diagnostic index was fitted with a binary logistic regression model, and the diagnostic accuracy was evaluated according to the receiver operating characteristic (ROC) curve. The sensitivity, specificity, predictive values (PV), and likelihood ratios (LR) were calculated.ResultA total of 210 febrile patients were enrolled, 53 patients were diagnosed with ATB (28 pathogen-confirmed vs. 25 clinically diagnosed) and 157 patients were non-ATB (84 with latent tuberculosis infection (LTBI) vs. 73 uninfected with MTB). Additionally, 30 pathogen-confirmed ATB patients were assembled. When diagnosing ATB, the area under the ROC curve (AUROC) of the MTB-specific triple-color FluoroSpot assay was significantly better than that of T-SPOT.TB (0.882 vs. 0.811, p = 0.017). With the fitted diagnostic index at a cutoff value of 0.378, the sensitivity, specificity, LR+, and LR- were 74.7%, 93.0%, 10.66, and 0.27, respectively. When differentiating ATB from LTBI, the AUROC of the FluoroSpot assay and T-SPOT.TB was 0.878 and 0.692, respectively (p < 0.001). With a diagnostic index of 0.413, the sensitivity, specificity, LR+, and LR were 77.1%, 85.7%, 5.40, and 0.27, respectively.ConclusionThe MTB-specific triple-color FluoroSpot (IFN-γ/IL-2/TNF-α) might be helpful for the differentiation of TB infection status in febrile patients.

Introduction: The necessity for tuberculosis preventive treatment (TPT) and routine T-SPOT.TB monitoring in patients with psoriasis and tuberculosis infection (TBI) undergoing interleukin (IL)-17A inhibitor therapy remains uncertain. This study aims to evaluate the long-term safety of IL-17A inhibitors administered without TPT and analyze changes in T-SPOT.TB among these patients. It also identifies risk factors for TBI in patients with psoriasis. Methods: This single-center prospective study enrolled adult patients with plaque psoriasis and TBI receiving IL-17A inhibitors. TBI was defined as positive T-SPOT.TB results (≥ 6 spots) without symptoms or evidence of active tuberculosis (ATB). TPT administration was based on contraindications, tuberculosis risk factors, and patient preferences. The primary endpoint was the incidence of ATB over 2 years. Secondary outcomes included T-SPOT.TB changes and TBI risk factors. Results: Of the 129 patients with psoriasis and TBI enrolled in the study, 97 (75.2%) did not receive TPT, while 32 (24.8%) did. Among them, 109 patients (84.5%) completed the 2-year follow-up. During the 235 person-years of observation, no ATB cases were identified. Median T-SPOT.TB values showed no significant changes from baseline to year 2 in both the non-TPT (20 vs. 17 spots, p = 0.975) and TPT groups (55 vs. 58 spots, p = 0.830). T-SPOT.TB reversed in 14 patients (12.8%), mostly in the non-TPT group. Moreover, for TBI risk factor analysis, a cohort of 212 patients with psoriasis with negative baseline T-SPOT.TB was evaluated, revealing a TBI prevalence of 37.8%. Logistic regression analysis highlighted age ≥ 45 years (odds ratio [OR] 2.44, 95% confidence interval [CI] 1.50–3.99, p < 0.001) and body mass index (BMI) < 24.0 kg/m2 (OR 2.12, 95% CI 1.27–3.54, p = 0.004) as independent risk factors for TBI. Conclusion: IL-17A inhibitors do not appear to reactivate tuberculosis in patients with psoriasis and TBI, potentially reducing the need for routine TBI screening and preventive treatment. Trial Registration: Chinese Clinical Trial Registry, ChiCTR2100045823. [ABSTRACT FROM AUTHOR]

BackgroundThe clinical challenge of differentiating suspected tuberculosis with positive T-SPOT.TB results persist. This study aims to investigate the utility of the Systemic Immune-Inflammation Index (SII), Fibrinogen, and T-SPOT.TB in distinguishing between active pulmonary tuberculosis (PTB) and non-tuberculous lung diseases.MethodsA retrospective analysis included 1,327 cases of active PTB with positive T-SPOT.TB results and 703 cases of non-tuberculous lung diseases from May 2016 to December 2020 at Meizhou People’s Hospital. These were designated as the case group and the control group, respectively. The detection indicators of T-SPOT.TB: Early Secreted Antigenic Target 6 (ESAT-6), Culture Filtrate Protein 10 (CFP-10), as well as SII and Fibrinogen levels—were compared and analyzed for association and joint diagnostic value between the two groups.ResultsThe case group showed higher values of ESAT-6, CFP-10, SII, and Fibrinogen compared to the control group (all p < 0.001). In the case group, SII and Fibrinogen did not correlate with ESAT-6 and CFP-10 (∣rs∣ all < 0.3) but were positively correlated with C-reactive protein (CRP; rs all > 0.3). SII and Fibrinogen values in smear-positive pulmonary tuberculosis were higher than in smear-negative cases (all p < 0.05). The optimal diagnostic thresholds for ESAT-6, CFP-10, SII, and Fibrinogen in differentiating between active PTB and non-tuberculous lung diseases were 21.50 SFCs/106 PBMC, 22.50 SFCs/106 PBMC, 2128.32, and 5.02 g/L, respectively. Regression logistic analysis showed that ESAT-6

Tuberculosis (TB) remains a leading cause of death globally. Identifying the factors associated with mortality during hospitalization for TB is crucial for improving patient outcomes. This study aimed to investigate the potential risk factors, including T-SPOT.TB test results and routine laboratory markers of inflammation, associated with death during hospitalization due to TB. A retrospective analysis was conducted on 244 hospitalized TB patients. Demographic data, clinical characteristics, T-SPOT.TB results, and laboratory parameters were collected. Univariate and multivariate analyses were performed to identify independent risk factors for in-hospital mortality. Among the patients, 206 survived and 38 died during hospitalization. Multivariate analysis revealed that age (HR: 1.08, 95% CI: 1.02–1.15, p = 0.001), a negative T-SPOT.TB test result (HR: 4.01, 95% CI: 1.78–9.01, p < 0.001), elevated C-reactive protein (CRP) levels (HR: 1.04, 95% CI: 1.01–1.08, p = 0.007), and increased neutrophil-to-lymphocyte ratio (NLR) (HR: 1.04, 95% CI: 1.00–1.07, p = 0.025) were independent risk factors for mortality. This study identified age, a negative T-SPOT.TB result, elevated CRP levels, and a high NLR as significant independent risk factors for death in hospitalized TB patients. These findings underscore the importance of these parameters in the risk stratification and management of hospitalized TB patients. Further research is warranted to elucidate the mechanisms behind these associations and to validate these results in different populations. [ABSTRACT FROM AUTHOR]

Similar clinical features make the differential diagnosis difficult, particularly between lung cancer and pulmonary tuberculosis (TB), without pathological evidence for patients with concomitant TB infection. Our study aimed to build a nomogram to predict malignant pulmonary lesions applicable to clinical practice. We retrospectively analyzed clinical characteristics, imaging features, and laboratory indicators of TB infection patients diagnosed with lung cancer or active pulmonary TB at Xiangya Hospital of Central South University. A total of 158 cases from January 1, 2018 to May 30, 2019 were included in the training cohort. Predictive factors for lung cancer were screened by a multiple-stepwise logistic regression analysis. A nomogram model was established, and the discrimination, stability, and prediction performance of the model were analyzed. A total of 79 cases from June 1, 2019, to December 30, 2019, were used as the validation cohort to verify the predictive value of the model. Eight predictor variables, including age, pleural effusion, mediastinal lymph node, the number of positive tumor markers, the T cell spot test for TB, pulmonary lesion morphology, location, and distribution, were selected to construct the model. The corrected C-statistics and the Brier scores were 0.854 and 0.130 in the training cohort, and 0.823 and 0.163 in the validation cohort. Calibration plots showed good performance, and decision curve analysis indicated a high net benefit. In conclusion, the nomogram model provides an effective method to calculate the probability of lung cancer in TB infection patients, and it has excellent discrimination, stability, and prediction performance in detecting a malignant diagnosis of undiagnosed pulmonary lesions.

Infants who are human immunodeficiency virus (HIV)-exposed uninfected (iHEU) experience higher risk of infectious morbidity than infants HIV-unexposed uninfected (iHUU). We compared tuberculosis (TB) infection prevalence in 418 Bacillus Calmette-Guérin vaccinated sub-Saharan African iHEU and iHUU aged 9–18 months using T-SPOT.TB. Prevalence of TB infection was low and did not differ by HIV exposure status. [ABSTRACT FROM AUTHOR]

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.

Hemodialysis (HD) patients should be screened for latent tuberculosis (TB) infection. We aimed to determine the frequency of latent TB infection in HD patients and to compare the effectiveness of the tests used. The files of 56 HD patients followed between 1 January 2021 and 1 October 2022 were retrospectively analyzed. Demographic data, the presence of the Bacillus Calmette-Guerin (BCG) vaccine, whether or not the patients had previously received treatment for TB before, the status of encountering a patient with active TB of patients over 18 years of age, without active tuberculosis and who had a T-SPOT.TB test or a Tuberculin Skin Test (TST) were obtained from the patient files. The presence of previous TB in a posterior–anterior (PA) chest X-ray was obtained by evaluating PA chest X-rays taken routinely. Of the patients, 60.7% (n = 34) were male and their mean age was 60.18 ± 14.85 years. The mean duration of dialysis was 6.43 ± 6.03 years, and 76.8% (n = 43) had 2 BCG scars. The T-SPOT.TB test was positive in 32.1% (n = 18). Only 20 patients (35.7%) had a TST and all had negative results. While the mean age of those with positive T-SPOT.TB results was higher (p = 0.003), the time taken to enter HD was shorter (p = 0.029). T-SPOT.TB test positivity was higher in the group that had encountered active TB patients (p = 0.033). However, no significant difference was found between T-SPOT.TB results according to BCG vaccine, albumin, urea and lymphocyte levels. Although T-SPOT.TB test positivity was higher in patients with a previous TB finding in a PA chest X-ray, there was no statistically significant difference (p = 0.093). The applicability of the TST in the diagnosis of latent TB infection in HD patients is difficult and it is likely to give false-negative results. The T-SPOT.TB test is not affected by the BCG vaccine and immunosuppression. Therefore, using the T-SPOT.TB test would be a more appropriate and practical approach in the diagnosis of latent TB in HD patients. [ABSTRACT FROM AUTHOR]

Yidan Sun,1– 3,&ast; Xiaozhou Yao,1– 3,&ast; Yingmeng Ni,1– 3 Yibing Peng,4 Guochao Shi1– 3 1Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Institute of Respiratory Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases, Shanghai, People’s Republic of China; 4Faculty of Medical Laboratory Science, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guochao Shi, Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, People’s Republic of China, Tel +86-13918462035, Fax + 021-64314162, Email shiguochao@hotmail.com Yibing Peng, Faculty of Medical Laboratory Science, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, People’s Republic of China, Tel +86-13795243560, Email pyb9861@sina.comPurpose: To explore the diagnostic efficacy and optimal diagnosis threshold of T-SPOT.TB for active tuberculosis in adults and to evaluate the influential factors for T-SPOT.TB results.Patients and Methods: A retrospective study of 1193 adult inpatients from April 2015 to March 2018 in Ruijin Hospital was conducted. All included patients underwent T-SPOT.TB assay, and were divided into two groups, active tuberculosis (ATB) and non-active tuberculosis (non-ATB) groups. Their demographic data, underlying diseases, personal history and laboratory findings were collected to calculate the diagnostic efficacy at different diagnosis thresholds and analyze the impact factors. Symptoms and imaging features of ATB patients were recorded and analyzed.Results: A total of 114 ATB patients and 1079 non-ATB patients were included in the study, and ATB patients had a higher level of T-SPOT.TB than the non-ATB group. Sensitivity and specificity of T-SPOT.TB for diagnosing ATB are 78.95% and 68.58% as the threshold at 6sfu. In the diagnosis accordance curves, ESAT-6, CFP-10, and max (ESAT-6 or CFP-10) reached the plateau at 40sfu, while sum (ESAT-6 and CFP-10) reached the plateau at 70sfu. Multivariate logistic regression analysis showed that obsolescent tuberculosis (p=0.001), smoking history(p=0.005), diabetes(p=0.035) and advanced age (≥ 65 years old) (p=0.031) were risk factors for false-positive result of T-SPOT.TB. In terms of imaging features, logistic regression analysis suggested that the thin-wall cavitary lesion was the only feature associated with the result of T-SPOT.TB.Conclusion: As for using T-SPOT.TB test to diagnose active tuberculosis, increased threshold could significantly elevate the diagnosis accordance. And we suggest that the threshold of T-SPOT.TB could be increased to 40sfu for diagnosing ATB. Attention should be paid when diagnose ATB in population with obsolescent tuberculosis, smoking history, diabetes and advanced age, for the risk of false-positive.Keywords: T-SPOT.TB, active tuberculosis, diagnosis threshold

Recombinant technologies have been long widely used in medicine. This article presents a review on the application of medical technologies based on ESAT-6 and CFP-10 proteins in diagnostics and prevention of tuberculosis. ESAT-6 and CFP-10 are specific proteins whose genes are encoded in the RD-1 zone (region of difference) of M. tuberculosis. M. bovis BCG and in most nontuberculous mycobacteria lack the RD-1 genome fragment. The discovery of ESAT-6 and CFP-10 antigens allowed to make the first and so far, the only breakthrough in improving the diagnostics of latent tuberculosis infection after the first tuberculin skin test (TST) was implemented. The article describes the principle of action and the experience with diagnostic tools based on ESAT-6 and CFP-10 such as in vitro interferon-gamma release assays (IGRA) and in vivo recombinant tuberculosis allergen (RTA, Diaskintest). RTA is inoculated intradermally similar to TST followed by developing delayed-type immune reaction detected in the area closest to M. tuberculosis. Combined use of ESAT-6 and CFP-10 for early detection of tuberculosis infection allowed to ameliorate for many drawbacks related to TST. High sensitivity and specificity was confirmed for ESAT-6- and CFP-10-based tests, so that former BCG vaccination had no more effect on test results and lowered frequency of false positive results due to reaction to non-tuberculous mycobacteria. The results of a large-scale meta-analysis on studies with patients at high risk demonstrated that the risk of developing tuberculosis in subjects with positive vs. negative IGRA was increased by 9.35-fold (95% confidence interval (CI [6.4813.49]), whereas for TST by 4.24-fold (95% CI [3.35.46]). 95.1%, (95% CI [95.0695.1]). Analyzing available publications demonstrated sufficient evidence base regarding efficacy of using ESAT-6CFP-10-based tests in tuberculosis diagnostics. Finally, there are also reviewed the diagnostic tests and vaccines based on using such proteins currently being under development.

Zhen-Zhen Wang,1 Hongsheng Wang1,2 1Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, People’s Republic of China; 2Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Hongsheng Wang, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, St. 12 Jiangwangmiao, Nanjing, Jiangsu, People’s Republic of China, Tel +86 13002571330, Fax +86 25-85478953, Email whs33@vip.sina.comAbstract: Lupus vulgaris is a paucibacillary form of cutaneous tuberculosis (CTB) which is accounting for 1– 2% of all tuberculosis cases. Here, we report a rare huge lupus vulgaris misdiagnosed as sarcoidosis for 11 years. A 65-year-old man presented to dermatology outpatient with a large asymptomatic erythematous plaque and erosions on his neck. Sarcoidosis was initially diagnosed on the basis of negative interferon-gamma release tests and biopsies of lymph nodes and lesions. The patient was treated with long-term oral steroid and immunosuppressive agents, but the lesions expanded gradually. Lupus vulgaris was finally diagnosed by combining molecular detection and mycobacterial culture. The skin lesions were resolved after six months of standard antituberculosis therapy. We report this case to analyze the reasons for the misdiagnosis and review-related literature to further provide experience for the diagnosis and treatment of cutaneous tuberculosis with negative T-SPOT.TB.Keywords: lupus vulgaris, cutaneous tuberculosis, diagnosis, T-SPOT.TB

Background. Tuberculosis associated with HIV infection is becoming almost a new disease, where not only new approaches to treatment are being formed, but there is also a need to improve the quality and search for new means of early diagnosis of tuberculosis infection.The aim. To evaluate the diagnostic performance of the T-SPOT.TB test for the detection of latent tuberculosis infection and clinical forms of tuberculosis in patients with HIV infection.Materials and methods. 396 patients registered at the AIDS Center for more than a year were examined. Everyone underwent standard examinations for pulmonary tuberculosis using sputum bacterioscopy techniques with Ziehl – Neelsen staining; a molecular genetic method based on hybridization technology – HAIN-GenoType MTBDRplus; crops on liquid media in the automated BACTEC MGIT 960 system and on Löwenstein–Jensen dense medium. T-SPOT.TB was conducted as a screening for everyone. With positive T-SPOT.TB results, negative results of the MBT search, absence of specific changes on the X-ray a conclusion was made about latent tuberculosis infection. Statistical data processing was carried out using the software package Statistica 10 (StatSoft Inc., USA).Results. According to the results of a comprehensive examination, tuberculosis was diagnosed in 174 patients, verified using various methods of searching for Mycobacterium tuberculosis in 116 patients (66.6 %). Infiltrative (63.8 %) and disseminated (24.7 %) tuberculosis were more often diagnosed. Latent tuberculosis infection was diagnosed in 52 patients, 170 HIV-infected patients have no data for tuberculosis at this stage.Conclusions. T-SPOT.TB can be used in the diagnostic complex of monitoring patients with HIV infections – as a screening method to detect latent tuberculosis, for preventive chemotherapy.

ABSTRACT The objectives of this study were to screen for latent tuberculosis infection (LTBI) among patients with systemic lupus erythematosus (SLE) using the T-SPOT.TB assay and to identify factors affecting the assay results. SLE patients were enrolled from 13 tertiary hospitals in eastern, central, and western China from September 2014 to March 2016 and were screened using the T-SPOT.TB assay to detect LTBI. Basic information about the subjects was collected, including gender, age, body mass index (BMI), course of disease, evidence of previous tuberculosis, Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, and the use of glucocorticoids and immunosuppressants. Univariate analysis and multivariable logistic regression were performed to identify factors affecting the results of the T-SPOT.TB assay. In all, 2,229 SLE patients were screened using the T-SPOT.TB assay, of whom 334 patients tested positive, yielding a positivity rate of 15% (95% confidence interval [CI], 13.5% to 16.5%). The positivity rate was higher in male than female patients and had an increasing trend with age. Multivariable logistic regression analysis showed that patients over 40 (odds ratio [OR], 1.65; 95% CI, 1.29 to 2.10) and with evidence of previous tuberculosis (OR, 4.43; 95% CI, 2.81 to 6.99) were more likely to have positive T-SPOT.TB results, while patients with a SLEDAI-2K score of ≥10 (OR, 0.61; 95% CI, 0.43 to 0.88), a glucocorticoid dose of ≥60 mg/d (OR, 0.62; 95% CI, 0.39 to 0.98), leflunomide (LEF) treatment (OR, 0.51; 95% CI, 0.29 to 0.88), or tacrolimus (FK506) treatment (OR, 0.40; 95% CI, 0.16 to 1.00) were more likely to have negative T-SPOT.TB results. The frequencies of CFP-10–specific gamma interferon (IFN-γ)-secreting T cells were significantly lower in SLE patients with severe disease activity or high-dose glucocorticoids (P

Background: Tuberculosis is an airborne infectious disease with multiple morphologic changes on chest imaging. Tuberculosis-specific enzyme-linked immunospot assay (T-SPOT.TB) is widely used in the diagnosis of tuberculosis. Clinically, pulmonary tuberculosis with T-SPOT.TB negative and interstitial changes is very rare. Methods: T-SPOT.TB, pathogenetic testing, chest CT scan, next-generation sequencing (NGS). Results: Laboratory tests showed negative T-SPOT.TB and sputum antacid staining, chest CT showed interstitial fibrosis and multiple high-density shadows in both lungs, and sputum NGS showed Mycobacterium tuberculosis infection. Conclusions: Negative T-SPOT.TB and interstitial lung changes do not exclude Mycobacterium tuberculosis infection. NGS has a high specificity in the detection of pathogens in infectious diseases, especially in complex, mixed infectious diseases. [ABSTRACT FROM AUTHOR]

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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. [ABSTRACT FROM AUTHOR]

Background: T-SPOT.TB (T-SPOT) is widely used for the detection of Mycobacterium tuberculosis infection by detecting interferon-gamma (IFN-g) release in T lymphocytes. This assay is performed on peripheral blood mononuclear cells (PBMCs) separated by Ficoll density gradient centrifugation, which often contain some residual platelets. Here, we investigated the impact of platelets on T-SPOT assay and related mechanisms. Methods: The correlation between platelet count, platelet-to-lymphocyte ratio (PLR), and the IFN-g secreting T cells (ISCs) in positive control wells of T-SPOT assay were retrospectively analyzed. T-SPOT assay was performed with un-treated PBMCs, platelets-removed PBMCs, and platelets-enriched PBMCs to confirm the impact of platelets on T-SPOT assay. The activation of platelets and their impact on IFN-g production in T cells were detected by flow cytometry (FCM). Platelets and T cells were cultured in a mixed culture system and co-culture system respectively, followed by detection of the frequencies of IFN-γ-producing T cells and the levels of intracellular IFN-g in T cells by FCM. Moreover, the effect of platelet releasate on the T-SPOT assay was evaluated. Results: The ISCs in positive control wells of the T-SPOT assay showed a significant decrease with the increase in platelet count. The PLR of the peripheral blood were negatively correlated with the ISCs in positive control wells of the T-SPOT assay. Removal or enrichment of platelets significantly increased or decreased the ISCs and the positive rate of T-SPOT. Inhibition of platelet activation significantly increased the ISCs of T-SPOT. The frequencies of IFN-γ-producing T cells in PBMCs and the levels of intracellular IFN-g were significantly reduced by the addition of platelets, both in the mixed culture system and the co-culture system. Platelet releasate upon thrombin activation significantly decreased the ISCs of T-SPOT. Conclusions: Platelets correlate with negative T-SPOT results by inhibiting IFN-γ production in T cells via degranulation. [ABSTRACT FROM AUTHOR]

The way to monitor tuberculosis (TB) treatment is extremely lacking in clinical practice. The aim of the study is to assess the role of the TBAg/PHA ratio in the treatment monitoring of TB. TB patients were followed up for 6 months and serial T-SPOT.TB (T-SPOT) assays were performed. In patients with successful treatment outcomes, the ESAT-6 sfc, CFP-10 sfc, and TBAg/PHA ratio all showed a decreased trend after the initiation of treatment. Conversely, PHA sfc showed an increased trend after 2 months of treatment. However, these indicators had moderate performance in distinguishing between before and after 6 months of treatment, and the AUC ranged from 0.702 to 0.839. Notably, the TBAg/PHA ratio in patients without risk factors was of important value in differentiation between before and after treatment. The optimal AUC of TBAg/PHA ratio reached up to 0.890. Patients with unsuccessful treatment outcomes showed persistently high levels of TBAg/PHA ratio. The TBAg/PHA ratio in patients after 6 months of treatment showed a certain potential in distinguishing between patients with successful and unsuccessful treatment outcomes. A further calculation of the TBAg/PHA ratio in T-SPOT assay has potential value in the treatment monitoring of TB, but further confirmation is needed. [ABSTRACT FROM AUTHOR]

Abstract Background Immune checkpoint inhibitors are a standard treatment for advanced lung cancer, although it remains important to identify biomarkers that can accurately predict treatment response. Immune checkpoint inhibitors enhance the antitumor T‐cell response, and interferon‐γ plays an important role in this process. Therefore, this study evaluated whether the number of interferon‐γ‐releasing peripheral T cells after phytohemagglutinin stimulation in the interferon‐γ release assay might act as a biomarker for the response of non‐small cell lung cancer to immune checkpoint inhibitor treatment. Methods Data were retrospectively collected regarding 74 patients with non‐small cell lung cancer who had received immune checkpoint inhibitors. Pretreatment screening tests had been performed using the T‐SPOT.TB assay, which quantifies the number of interferon‐γ‐releasing T cells (as immunospots) in response to phytohemagglutinin and tuberculosis‐specific antigen stimulation. Clinical factors and the number of spots in the T‐SPOT fields were evaluated for associations with patient outcomes. The median number of spots was used to categorize patients as having high or low values, and the two groups were compared. Results Relative to patients with a low ratio, patients with a high ratio of phytohemagglutinin/tuberculosis‐specific antigen spots (i.e. more responsive T cells) had significantly better progression‐free survival after immune checkpoint inhibitor treatment. When we only considered patients with negative T‐SPOT results, a high number of phytohemagglutinin‐stimulated spots corresponded to significantly longer progression‐free survival. Conclusion The T‐SPOT.TB assay can be used to quantify the number of immunospots in response to antigen stimulation, which may predict the response to immune checkpoint inhibitors in patients with non‐small cell lung cancer.

Objective: This study aimed to compare the accuracy of QuantiFERON‐TB Gold Plus (QFT‐Plus) and T‐SPOT.TB for diagnosing active tuberculosis (ATB) in febrile patients, to explore influencing factors of positive results and to verify the potential value of QFT‐Plus in the identification of ATB and latent tuberculosis infection (LTBI). Methods: A total of 240 febrile patients with ATB (n = 80) and non‐ATB (n = 160) were recruited to assess the accuracy of QFT‐Plus and T‐SPOT.TB for diagnosing ATB. Multivariable logistic regression was used to analyze the influencing factors of positive results. Results: The proportion of indeterminate results (ITRS) in QFT‐Plus and T‐SPOT.TB were 3.3% and 0%, respectively. The consistency between the results of the QFT‐Plus and T‐SPOT.TB was substantial. The area under the receiver operating characteristic curve (AUROC) of the QFT‐Plus and T‐SPOT.TB for diagnosing ATB was 0.792 and 0.849 (p = 0.070), respectively. The sensitivity of differentiating ATB from non‐ATB was 92.2% in QFT‐Plus versus 95.0% in T‐SPOT.TB. The influencing factors of T‐SPOT.TB positive result were male (odds ratio (OR) = 2.33, 95% confidence interval (CI) 1.27–4.26, p = 0.006), evidence of previous TB (OR 11.36, 95% CI 4.62–27.94, p < 0.001), while male (OR = 3.17, 95% CI 1.73–5.84, p < 0.001), evidence of previous TB (OR = 7.58, 95% CI 3.60–15.98, p <0.001), and use of immunosuppressant (OR = 0.49, 95% CI 0.260.94, p = 0.030) were influencing factors for QFT‐Plus positive result. There was no significant difference in QFT‐Plus in differentiating ATB from LTBI in febrile patients. Conclusion: There was no significant difference between QFT‐Plus and T‐SPOT.TB for diagnosing ATB in febrile patients. QFT‐Plus is prone to ITRS. The influencing factors including males, evidence of the previous TB, and use of immunosuppressant should be considered when interpreting positive results. [ABSTRACT FROM AUTHOR]

For the immunodiagnosis of tuberculosis infection, in addition to standard skin tests (Mantoux test with 2 TU PPD-L and Diaskintest), in vitro tests are currently used, one of which is the T-spot.TB test.Purpose of research. Evaluate the T-SPOT test as a method of early detection of tuberculosis infection in children and adolescents and its role as an additional method in solving the problem of the need for chemoprophylaxis.Materials and methods. The analysis of the results of T-SPOT.TB in 794 children aged 2 to 17 years inclusive in the period from 2016 to 2019 was carried out. Two groups were allocated: 1 group (n = 596) — children who underwent T-SPOT.TB as the main methodology; Group 2 — 198 children with positive skin test results for a recombinant tuberculosis allergen after screening. The results of T-SPOT.TB were evaluated taking into account the data of previous immunodiagnostics and associated pathology.Results. It is established that T-SPOT.TB. can be used as an independent method in case of rejection of skin tests. The level of latent tuberculosis infection is higher among children with concomitant pathology according to the results of T-SPOT.TB twice.Conclusion. T-SPOT.TB can be an alternative method for diagnosing tuberculosis infection during screening. In children with concomitant pathology of the T-SPOT.TB can serve as the leading method of tuberculosis immunodiagnosis. A positive T-SPOT.TB can serve as an additional method for deciding on the appointment of preventive chemotherapy.

In addition to standard skin tests (Mantoux test with 2 TU PPD-L and diaskintest) for the diagnosis of tuberculosis infection, in vitro tests are used. One of these tests is T-SPOT.TB being more widely used in recent years.The objective: to evaluate the effectiveness of T-SPOT.TB test for early detection of tuberculosis infection in children and adolescents in Samara Region.Subjects and methods. From 2016 to 2019, results of T-SPOT.TB tests performed in 596 children aged 2 to 17 years inclusive were analyzed; those children had no immunodiagnosis of tuberculosis infection using skin tests since their parents refused to have it.Results. It was found out that the major reason for refusing skin tests was the “fear” of visiting a TB dispensary if the result had been positive — 38.43% (n = 229). The latent tuberculosis infection according to the results of T-SPOT.TB among children with concomitant pathology made 2.6%, among healthy children – 0.7%.Conclusion. T-SPOT.TB test may be used as an alternative method for diagnosis of tuberculosis infection, should the parent refuse to have skin tests. In children with concomitant pathology, T-SPOT.TB test can serve as a leading method for immunodiagnosis of tuberculosis.The authors state that they have no conflict of interests.

Latent Tuberculosis Infection (LTBI) is a state of persistent immune response to Mycobacterium tuberculosis complex antigens without clinical, radiological and microbiological signs of active disease. Effective diagnosis and preventive treatment of LTBI are crucial for tuberculosis (TB) control, especially in high-risk groups. Currently, two main tests are used for LTBI diagnosis: the Tuberculin Skin Test (TST) and the Interferon-Gamma Release Assays (IGRA), including the QuantiFERON-TB Gold Plus (QFT-Plus) and the T-SPOT.TB. Our study evaluated the performance of the T-SPOT.TB test in patients with indeterminate QFT-Plus results, using data from the Clinical Microbiology and Virology Laboratory (M&V) of Papa Giovanni XXIII Hospital in Bergamo, Italy. Blood samples from patients tested for LTBI with QFT-Plus from January 1, 2017 to May 15, 2024 were analyzed. The QFT-Plus is the most widely used test in routine diagnostics for LTBI screening due to the availability of automated systems. Out of 20,995 samples tested with QFT-Plus, 576 (2.7%) gave indeterminate results. In all cases of indeterminate QFT-Plus results, M&V recommends performing the T-SPOT.TB test. However, of the 576 patients who obtained an indeterminate outcome, only 137 (23.8%) followed the indication. The T-SPOT.TB provided a definitive result in 87.6% of the cases, resolving 120 (80 negative and 40 positive) of 137 indeterminate QFT-Plus outcomes. Specifically, 78 of 92 cases, equal to 84.8%, were settled when the T-SPOT. TB test was performed within 30 days of the QFT-Plus. The T-SPOT.TB test has shown potential effectiveness in addressing indeterminate QFT-Plus results (84.8% resolution), indicating its possible role as a complementary diagnostic tool for LTBI. The proposed algorithm for LTBI screening is based on national and international guidelines recommending the use of the TST and/or an IGRA test for individuals at risk. However, it particularly emphasizes the use of QFT-Plus, due to its practicality and rapid execution, while recommending the addition of the T-SPOT.TB within 30 days in cases of indeterminate QFT-Plus results. Nevertheless, the conclusions should be regarded as preliminary and require confirmation through larger or controlled studies., Competing Interests: Conflict of interest: None.

One-fourth of the world’s population has been infected with Mycobacterium tuberculosis (M.tb). Although interferon-gamma release assays (IGRAs) have been shown to be valid methods for identifying M.tb infection and auxiliary methods for diagnosis of active tuberculosis (TB), lower sensitivity and higher indeterminate rate were often detected among immunosuppressed patients. IP-10 was an alternative biomarker due to the higher expression level after M.tb antigen stimulation, but whether CXCL10 mRNA (the gene that transcribes for the IP-10 protein) can be used as a target for M.tb infection diagnosis was limited. Therefore, we aimed to evaluate the performance of a novel M.tb-specific CXCL10 mRNA release assay in diagnosis of M.tb infection. Suspected TB patients and healthy controls were prospectively recruited between March 2018 and November 2019 from three hospitals in China. CXCL10 mRNA release assay and traditional interferon-gamma release assay (T-SPOT.TB) were simultaneously performed on peripheral blood. Of the 1,479 participants enrolled in the study, 352 patients with definite TB and 153 healthy controls were analyzed. CXCL10 mRNA release assay provided a sensitivity of 93.9% (95% CI = 90.8–96.2%) and a specificity of 98.0% (95% CI = 94.3–99.6%) in the diagnosis of M.tb infection, respectively, while T-SPOT.TB gave a sensitivity of 94.5% (95% CI = 91.5–96.6%) and a specificity of 100% (95% CI = 97.6–100.0%) in the diagnosis of M.tb infection, respectively. The diagnostic performance of CXCL10 mRNA release assay was consistent with T-SPOT.TB, with a total coincidence rate of 95.0% (95% CI = 93.0–96.9%) and a Cohen’s kappa value of 0.89 (0.84–0.93, p < 0.001). However, among TB patients with HIV co-infection (n = 14), CXCL10 mRNA release assay presented significantly higher positive rate [92.9% (66.1–99.8%) vs. 61.5% (31.6–86.1%), p = 0.029] than those of T-SPOT.TB. These results suggested that M.tb-specific CXCL10 mRNA was a novel and useful target in the diagnosis of M.tb infection.

Background: Tuberculosis (TB) is a leading cause of fever of unknown origin (FUO). In recent years, interferon-γ release assays (IGRAs) have been widely utilized and the cut-off values given by the manufacturers are set in countries where rates of TB are not as high. Methods: A prospective cohort study was conducted in a Chinese general hospital to evaluate the diagnostic performance of T-SPOT.TB (T-SPOT) and QuantiFERON-TB Gold (QFT) in detecting active TB (ATB) in a high TB endemic area. Test results were compared with the culture and clinically confirmed diagnosis. Further, we explored an alternative method of interpreting IGRAs by increasing the cut-off values. Results: The sensitivity and specificity of T-SPOT in detecting ATB were 85.3% (95% CI 81.6–94.0%) and 71.8% (95% CI 67.3–76.0%), respectively. The sensitivity and specificity of QFT were 72.3% (95% CI 62.8–80.1%) and 77.0% (95% CI 72.7–80.8%), respectively. Receiver operating characteristic analysis was used for evaluation of different cut-off values. When the cut-off values were adjusted as 125 spot-forming cells (SFCs)/ 2.5*105 cells for T-SPOT and 4.0 IU/ml for QFT, the specificity could be improved to > 90.0% (90.3% and 94.1%, respectively), and the sensitivity were 43.1% and 41.6%, respectively. The new adjusted cut-off values were validated in another independent validation cohort. Conclusion: The adjusted cut-off values of the two assays considerably improved the diagnostic value when applied to FUO patients in clinical settings.

One-fourth of the world's population has been infected with Mycobacterium tuberculosis (M.tb). Although interferon-gamma release assays (IGRAs) have been shown to be valid methods for identifying M.tb infection and auxiliary methods for diagnosis of active tuberculosis (TB), lower sensitivity and higher indeterminate rate were often detected among immunosuppressed patients. IP-10 was an alternative biomarker due to the higher expression level after M.tb antigen stimulation, but whether CXCL10 mRNA (the gene that transcribes for the IP-10 protein) can be used as a target for M.tb infection diagnosis was limited. Therefore, we aimed to evaluate the performance of a novel M.tb -specific CXCL10 mRNA release assay in diagnosis of M.tb infection. Suspected TB patients and healthy controls were prospectively recruited between March 2018 and November 2019 from three hospitals in China. CXCL10 mRNA release assay and traditional interferon-gamma release assay (T-SPOT.TB) were simultaneously performed on peripheral blood. Of the 1,479 participants enrolled in the study, 352 patients with definite TB and 153 healthy controls were analyzed. CXCL10 mRNA release assay provided a sensitivity of 93.9% (95% CI = 90.8–96.2%) and a specificity of 98.0% (95% CI = 94.3–99.6%) in the diagnosis of M.tb infection, respectively, while T-SPOT.TB gave a sensitivity of 94.5% (95% CI = 91.5–96.6%) and a specificity of 100% (95% CI = 97.6–100.0%) in the diagnosis of M.tb infection, respectively. The diagnostic performance of CXCL10 mRNA release assay was consistent with T-SPOT.TB, with a total coincidence rate of 95.0% (95% CI = 93.0–96.9%) and a Cohen's kappa value of 0.89 (0.84–0.93, p < 0.001). However, among TB patients with HIV co-infection (n = 14), CXCL10 mRNA release assay presented significantly higher positive rate [92.9% (66.1–99.8%) vs. 61.5% (31.6–86.1%), p = 0.029] than those of T-SPOT.TB. These results suggested that M.tb -specific CXCL10 mRNA was a novel and useful target in the diagnosis of M.tb infection. [ABSTRACT FROM AUTHOR]

BackgroundsTakayasu arteritis (TAK) is a chronic, granulomatous vasculitis correlated with tuberculosis (TB). The two diseases share similar pathological characteristics and clinical manifestations which increase the difficulty to diagnose. Active tuberculosis (ATB) has implications for treatment strategies in TAK patients. Therefore, the investigation of clinical features and potential risk factors of ATB in TAK patients is vital.MethodsThe study reviewed hospitalized patients diagnosed with TAK in our hospital from 2008, to 2021. TAK patients with ATB were enrolled as the case group. The control group was randomly selected in a 3:1 ratio. The clinical characteristics of TAK patients with and without ATB were compared. Multivariate logistic regression analysis was performed to determine risk factors for ATB in TAK patients.ResultsWe reviewed 1,789 patients and ultimately identified 30 (1.7%) ATB cases. TAK patients with ATB were more prone to develop symptoms including fever (p=0.001), fatigue (p=0.003), cough (p=0.037), expectoration (p8 mg/L (OR 9.108; 95% CI, 1.096–75.711; p=0.041) and positive T-SPOT.TB result (OR 68.669; 95% CI, 7.291–646.738; p8 mg/L and positive T-SPOT.TB result were identified as independent risk factors for ATB in TAK patients.

Backgrounds: Takayasu arteritis (TAK) is a chronic, granulomatous vasculitis correlated with tuberculosis (TB). The two diseases share similar pathological characteristics and clinical manifestations which increase the difficulty to diagnose. Active tuberculosis (ATB) has implications for treatment strategies in TAK patients. Therefore, the investigation of clinical features and potential risk factors of ATB in TAK patients is vital. Methods: The study reviewed hospitalized patients diagnosed with TAK in our hospital from 2008, to 2021. TAK patients with ATB were enrolled as the case group. The control group was randomly selected in a 3:1 ratio. The clinical characteristics of TAK patients with and without ATB were compared. Multivariate logistic regression analysis was performed to determine risk factors for ATB in TAK patients. Results: We reviewed 1,789 patients and ultimately identified 30 (1.7%) ATB cases. TAK patients with ATB were more prone to develop symptoms including fever (p=0.001), fatigue (p=0.003), cough (p=0.037), expectoration (p<0.001), weight loss (p=0.003), and night sweating (p<0.001). Increased level of hypersensitive C reactive protein (hsCRP, p=0.001), decreased level of albumin (p=0.031), and higher positive rate of T-SPOT.TB test (p<0.001) were observed in the case group. Multivariate logistic regression analysis revealed that hsCRP >8 mg/L (OR 9.108; 95% CI, 1.096–75.711; p=0.041) and positive T-SPOT.TB result (OR 68.669; 95% CI, 7.291–646.738; p<0.001) were risk factors for ATB in TAK patients. The proportion of patients undergoing subsequent surgery for Takayasu arteritis was lower in patients with ATB (p<0.001). Conclusion: Our study suggested that the diagnosis of ATB should be considered when TAK patients experienced symptoms including fever, fatigue, weight loss, etc. hsCRP >8 mg/L and positive T-SPOT.TB result were identified as independent risk factors for ATB in TAK patients. [ABSTRACT FROM AUTHOR]

Aims The study aimed to investigate the clinical characteristics of patients with pleural effusion (PE), and explore the effective indicators for definite diagnosis of tuberculous pleural effusion (TBPE).Methods The adult patients with the presence of PE were enrolled. All the patients received pleural fluid Mycobacterium tuberculosis DNA detection, ADA activity measure and blood T-SPOT.TB test. The clinical characteristics and examination results were recorded.Results A total of 77 PE patients, including 30 (38.96%) TBPE, 19 (24.67%) malignant PE, 6 (7.79%) empyema, 10 (12.99%) parapneumonic effusion and 12 (15.58%) miscellaneous causes, were enrolled. The diagnostic sensitivity and specificity of pleural fluid M. tuberculosis DNA detection were 33.3% and 100%, respectively. The diagnostic parameters of pleural fluid ADA for TBPE were as follows: sensitivity 50% and specificity 78.7%. In PE cases with pleural fluid lactate dehydrogenase (LDH) more than 500 U/L, the diagnostic values of DNA detection and ADA activity were enhanced, and DNA detection was superior to ADA activity. In addition, the ratio of blood T-STOP.TB A + B to lymphocyte was a potential diagnostic biomarker for TBPE with the sensitivity of 83.3% and the specificity of 66.0%.Conclusion The clinical significance of pleural fluid M. tuberculosis DNA detection is superior to ADA activity in the diagnosis of TBPE, especially in PE cases with LDH value more than 500 U/L. The ratio of blood T-STOP.TB A + B to lymphocyte is a potential indicator for definite diagnosis of TBPE, with high sensitivity.

Abstract Background Previous qualitative studies suggested that the false negative rate of the T cell spot test for tuberculosis infection (T-SPOT.TB) is associated with many risk factors in tuberculosis patients. However, more precise quantitative studies are lacking. The purpose of this study was to investigate the factors affecting quantified spot-forming cells (SFCs) to early secreted antigenic target 6 kDa (ESAT-6) or culture filtrate protein 10 kDa (CFP-10) in patients with active tuberculosis. Methods We retrospectively analyzed the data of 360 patients who met the inclusion criteria. Using the SFCs to ESAT-6 or CFP-10 levels as dependent variables, variables with statistical significance in the univariate analysis were subjected to optimal scaling regression analysis. The combination of ESAT-6 and CFP-10 (i.e., T-SPOT.TB) was analyzed by the exact logistic regression model. Results The results showed that the SFCs to ESAT-6 regression model had statistical significance (P

Abstract Background To investigate the diagnostic value of the interferon-γ release assay (IGRA) for detecting tuberculosis (TB) infection in patients with Behçet’s disease (BD). Methods We retrospective analyzed the data collected from 173 BD patients hospitalized between 2010 and 2015. Ninety-nine healthy volunteers were enrolled as a control group. IGRA was performed using T-SPOT.TB. The diagnosis of active TB (ATB) was based on clinical, radiological, microbiological, histopathological information and the response to anti-TB therapy. Latent TB (LTB) infection was defined as asymptomatic patients with positive T-SPOT.TB. Results TB infection was documented in 59 BD patients (34.1%). The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio of T-SPOT.TB for the diagnosis of ATB were 88.9%, 74.8%, 29.1%, 98.3%, 3.53 and 0.15, respectively. The receiver-operating-characteristic curve demonstrated that spot-forming cells (SFCs) of 70/106 PBMC was the optimal cutoff for diagnosing ATB, with an area under the curve of 0.891. Furthermore, the median SFCs in ATB group was significantly higher than those in LTB infection (466/106 PBMC vs. 68/106 PBMC, p = 0.007) or previous TB infection (466/106 PBMC vs. 96/106 PBMC, p = 0.018). A significant discrepancy between T-SPOT.TB and tuberculin skin test was noted (kappa coefficient = 0.391, p = 0.002). Conclusions T-SPOT.TB, an IGRA, may assist in the diagnosis of ATB in BD patients, and the higher SFCs suggest ATB in BD patients.

Background: Infections are one of the most common causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE). SLE patients have a higher risk of tuberculosis (TB) infection due to impaired immune defence. Objectives: To investigate the demographics, clinical characteristics and outcomes of patients with SLE and concomitant TB. Methods: Medical records of SLE patients with TB who were admitted to Peking Union Medical College (PUMC) Hospital in 1983–2019 were retrospectively reviewed. Age‐ and sex‐matched SLE inpatients without TB were randomly selected as controls. Clinical and laboratory features and treatment were analysed and compared, and subjects were followed up to assess their outcome. Results: Of the 10 469 SLE inpatients, 249 (2.4%) were diagnosed with TB. Compared with controls, SLE/TB + patients exhibited higher frequency of prior haematologic, mucocutaneous and musculoskeletal system involvement, and prior treatment with potent glucocorticoid/immunosuppressive agents (GC/ISA). Arthritis and alopecia, positive T‐SPOT.TB test and lymphocytopenia were more common in SLE/TB + patients. SLE/TB + patients with lupus before TB (SLE → TB) had higher risk of miliary TB (22.8%) and intracranial TB (16.5%) than SLE/TB + patients with lupus after TB (TB → SLE). SLE/TB + patients exhibited shorter long‐term survival than SLE/TB‐ patients; those with poorer in‐hospital outcomes had more severe lymphocytopenia and had received less treatment with ISAs. Conclusion: Systemic lupus erythematosus patients treated vigorously with GC/ISA should be alerted of increased risk of TB infection, especially miliary and intracranial TB. Positive T‐SPOT.TB and lymphocytopenia served as discriminatory variables between SLE/TB + and SLE/TB‐ patients. Lymphocytopenia was associated with poorer outcomes in SLE/TB + patients. [ABSTRACT FROM AUTHOR]

BackgroundDistinguishing between active tuberculosis (ATB) and latent tuberculosis infection (LTBI) remains challenging.MethodsBetween 2013 and 2019, 2,059 (1,097 ATB and 962 LTBI) and another 883 (372 ATB and 511 LTBI) participants were recruited based on positive T-SPOT.TB (T-SPOT) results from Qiaokou (training) and Caidian (validation) cohorts, respectively. Blood routine examination (BRE) was performed simultaneously. Diagnostic model was established according to multivariate logistic regression.ResultsSignificant differences were observed in all indicators of BRE and T-SPOT assay between ATB and LTBI. Diagnostic model built on BRE showed area under the curve (AUC) of 0.846 and 0.850 for discriminating ATB from LTBI in the training and validation cohorts, respectively. Meanwhile, TB-specific antigens spot-forming cells (SFC) (the larger of early secreted antigenic target 6 and culture filtrate protein 10 SFC in T-SPOT assay) produced lower AUC of 0.775 and 0.800 in the training and validation cohorts, respectively. The diagnostic model based on combination of BRE and T-SPOT showed an AUC of 0.909 for differentiating ATB from LTBI, with 78.03% sensitivity and 90.23% specificity when a cutoff value of 0.587 was used in the training cohort. Application of the model to the validation cohort showed similar performance. The AUC, sensitivity, and specificity were 0.910, 78.23%, and 90.02%, respectively. Furthermore, we also assessed the performance of our model in differentiating ATB from LTBI with lung lesions. Receiver operating characteristic analysis showed that the AUC of established model was 0.885, while a threshold of 0.587 yield a sensitivity of 78.03% and a specificity of 85.69%, respectively.ConclusionsThe diagnostic model based on combination of BRE and T-SPOT could provide a reliable differentiation between ATB and LTBI.

Background: Distinguishing between active tuberculosis (ATB) and latent tuberculosis infection (LTBI) remains challenging. Methods: Between 2013 and 2019, 2,059 (1,097 ATB and 962 LTBI) and another 883 (372 ATB and 511 LTBI) participants were recruited based on positive T-SPOT.TB (T-SPOT) results from Qiaokou (training) and Caidian (validation) cohorts, respectively. Blood routine examination (BRE) was performed simultaneously. Diagnostic model was established according to multivariate logistic regression. Results: Significant differences were observed in all indicators of BRE and T-SPOT assay between ATB and LTBI. Diagnostic model built on BRE showed area under the curve (AUC) of 0.846 and 0.850 for discriminating ATB from LTBI in the training and validation cohorts, respectively. Meanwhile, TB-specific antigens spot-forming cells (SFC) (the larger of early secreted antigenic target 6 and culture filtrate protein 10 SFC in T-SPOT assay) produced lower AUC of 0.775 and 0.800 in the training and validation cohorts, respectively. The diagnostic model based on combination of BRE and T-SPOT showed an AUC of 0.909 for differentiating ATB from LTBI, with 78.03% sensitivity and 90.23% specificity when a cutoff value of 0.587 was used in the training cohort. Application of the model to the validation cohort showed similar performance. The AUC, sensitivity, and specificity were 0.910, 78.23%, and 90.02%, respectively. Furthermore, we also assessed the performance of our model in differentiating ATB from LTBI with lung lesions. Receiver operating characteristic analysis showed that the AUC of established model was 0.885, while a threshold of 0.587 yield a sensitivity of 78.03% and a specificity of 85.69%, respectively. Conclusions: The diagnostic model based on combination of BRE and T-SPOT could provide a reliable differentiation between ATB and LTBI. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors are a standard treatment for advanced lung cancer, although it remains important to identify biomarkers that can accurately predict treatment response. Immune checkpoint inhibitors enhance the antitumor T‐cell response, and interferon‐γ plays an important role in this process. Therefore, this study evaluated whether the number of interferon‐γ‐releasing peripheral T cells after phytohemagglutinin stimulation in the interferon‐γ release assay might act as a biomarker for the response of non‐small cell lung cancer to immune checkpoint inhibitor treatment. Methods: Data were retrospectively collected regarding 74 patients with non‐small cell lung cancer who had received immune checkpoint inhibitors. Pretreatment screening tests had been performed using the T‐SPOT.TB assay, which quantifies the number of interferon‐γ‐releasing T cells (as immunospots) in response to phytohemagglutinin and tuberculosis‐specific antigen stimulation. Clinical factors and the number of spots in the T‐SPOT fields were evaluated for associations with patient outcomes. The median number of spots was used to categorize patients as having high or low values, and the two groups were compared. Results: Relative to patients with a low ratio, patients with a high ratio of phytohemagglutinin/tuberculosis‐specific antigen spots (i.e. more responsive T cells) had significantly better progression‐free survival after immune checkpoint inhibitor treatment. When we only considered patients with negative T‐SPOT results, a high number of phytohemagglutinin‐stimulated spots corresponded to significantly longer progression‐free survival. Conclusion: The T‐SPOT.TB assay can be used to quantify the number of immunospots in response to antigen stimulation, which may predict the response to immune checkpoint inhibitors in patients with non‐small cell lung cancer. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV) infected individuals are at increased risk of developing active tuberculosis (TB). TB incidence remains higher than in non-HIV subjects after antiretroviral therapy (ART) initiation. This study was conducted to estimate the prevalence of positive IGRA, reflecting latent tuberculosis infection and/or a history of active TB, in HIV-infected individuals after ART initiation in Japan. Two IGRAs (Interferon (IFN)-γ release assays), QuantiFERON®-TB Gold Plus (QFT-Plus) and T-Spot®. TB (TSPOT), were used. We also analyzed the TB associated risk factors for the IGRAs results and the role of CD4+ T-cells, CD8+ T-cells and NK cells for producing IFN-γ. We also analyzed the risk factors for positive IGRA responses and the role of CD4+ T-cells, CD8+ T-cells and NK cells for producing IFN-γ. One hundred eight-four subjects were prospectively enrolled. Median age was 49 years. The positivity rates of QFT-Plus and TSPOT were 7.6% [95%CI 4.6–12.4] and 2.7% [95%CI 1.2–6.2], respectively, with significant difference. TB-associated risk factors and NK cells ≥300/μL were selected as independently significant factors by multivariate logistic regression. The NK cell count revealed significant linear regression with IFN-γ production responding to TB-specific antigens. The prevalence of positive IGRAs was 2.7%–7.6%. QFT-Plus would be practical for a higher positivity rate and reflect TB risk factors. The innate immune system, referring to IFN-γ production, plays an important role in the immune response to TB-specific antigens even after initiating ART. [ABSTRACT FROM AUTHOR]

BackgroundThe prompt diagnosis of pulmonary tuberculosis (PTB) remains a challenge in clinical practice. The present study aimed to optimize an algorithm for rapid diagnosis of PTB in a real-world setting.Methods28,171 adult inpatients suspected of having PTB in China were retrospectively analyzed. Bronchoalveolar lavage fluid (BALF) and/or sputum were used for acid-fast bacilli (AFB) smear, Xpert MTB/RIF (Xpert), and culture. A positive mycobacterial culture was used as the reference standard. Peripheral blood mononuclear cells (PBMC) were used for T-SPOT.TB. We analyzed specimen types’ effect on these assays’ performance, determined the number of smears for diagnosing PTB, and evaluated the ability of these assays performed alone, or in combination, to diagnose PTB and nontuberculous mycobacteria (NTM) infections.ResultsSputum and BALF showed moderate to substantial consistency when they were used for AFB smear or Xpert, with a higher positive detection rate by BALF. 3-4 smears had a higher sensitivity than 1-2 smears. Moreover, simultaneous combination of AFB and Xpert correctly identified 44/51 of AFB+/Xpert+ and 6/7 of AFB+/Xpert- cases as PTB and NTM, respectively. Lastly, when combined with AFB/Xpert sequentially, T-SPOT showed limited roles in patients that were either AFB+ or Xpert+. However, T-SPOTMDC (manufacturer-defined cut-off) showed a high negative predicative value (99.1%) and suboptimal sensitivity (74.4%), and TBAg/PHA (ratio of Mycobacterium tuberculosis-specific antigens to phytohaemagglutinin spot-forming cells, which is a modified method calculating T-SPOT.TB assay results) ≥0.3 demonstrated a high specificity (95.7%) and a relatively low sensitivity (16.3%) in AFB-/Xpert- patients.ConclusionsConcurrently performing AFB smear (at least 3 smears) and Xpert on sputum and/or BALF could aid in rapid diagnosis of PTB and NTM infections in a real-world high-burden setting. If available, BALF is preferred for both AFB smear and Xpert. Expanding this algorithm, PBMC T-SPOTMDC and TBAg/PHA ratios have a supplementary role for PTB diagnosis in AFB-/Xpert- patients (moderately ruling out PTB and ruling in PTB, respectively). Our findings may also inform policy makers’ decisions regarding prevention and control of TB in a high burden setting.

BackgroundT-SPOT TB (T-SPOT) assay is widely used for detection of Mycobacterium tuberculosis infection that is based on the detection of M. tuberculosis-specific interferon-γ-secreting T cells (ISCs) in peripheral blood mononuclear cells (PBMCs). Recently, high frequencies of low-density granulocytes (LDGs) were found in the PBMCs of tuberculosis patients. Whether these LDGs affect the detection of T-SPOT has not been investigated. The impact of LDGs on T-SPOT assay and related mechanism were investigated in this study.MethodsThe correlations between the frequencies of LDGs and the results of T-SPOT were analyzed. T-SPOT with LDG-removed PBMCs and PBMCs with exogenous addition of LDGs were performed. The possible mechanism was explored by detecting the levels of negative immune regulatory molecules on LDGs. The impact of programmed death ligand 1 (PD-L1) on T-SPOT was evaluated and confirmed by function blocking with neutralizing antibody.ResultsThe positive rates of T-SPOT and ISCs in tuberculosis patients with low LDGs frequency (n = 22) were significantly higher than those with high LDGs frequency (n = 39). Removal or exogenous addition of LDGs significantly increased or decreased the ISCs and the positive rate of T-SPOT. The frequencies of interferon-γ-producing T cells were negatively correlated with the frequencies of LDGs. The expression of PD-L1 was significantly elevated on LDGs. Pretreatment of LDGs with anti-PD-L1 antibody significantly counteracted the impact of LDGs on T-SPOT. Treatment of PBMCs with anti-PD-L1 antibody resulted in comparable ISCs with that of LDG removal.ConclusionLDGs can inhibit the production of interferon-γ in T cells and decrease the positive rated of T-SPOT assay via highly expressed PD-L1.

Background: The role of T-SPOT.TB (T-SPOT) assay for tuberculous meningitis (TBM) diagnosis has not been fully assessed. Here, we conducted an updated meta-analysis to evaluate the diagnostic accuracy of peripheral blood (PB) T-SPOT and cerebrospinal fluid (CSF) T-SPOT for diagnosing TBM.Methods: Relevant studies in the PubMed database, EmBase database, Cochrane database, Scopus database, Google Scholar, China National Knowledge Internet, and Wan-Fang database were retrieved from August 1, 2005, to June 22, 2020. Statistical analysis was performed using Stata, Revman, and Meta-Disc software. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), summary receiver operating characteristic curves, and the area under the curve were determined and analyzed.Results: A total of 27 studies were eligible for inclusion within the meta-analysis. The pooled sensitivity and specificity of PB T-SPOT for TBM diagnosis were 0.78 (95% CI, 0.76–0.81) and 0.68 (95% CI, 0.66–0.71), respectively, whereas the pooled PLR, NLR, and DOR were 2.80 (95% CI, 2.29–3.42), 0.32 (95% CI, 0.27–0.38), and 10.08 (95% CI, 7.21–14.08), respectively. On the other hand, the pooled sensitivity and specificity of CSF T-SPOT on diagnosing TBM were 0.76 (95% CI, 0.72–0.80) and 0.88 (95% CI, 0.85–0.90), respectively, whereas the pooled PLR, NLR, and DOR were 5.92 (95% CI, 4.25–8.25), 0.28 (95% CI, 0.21–0.39), and 29.05 (95% CI, 16.40–51.45), respectively. The area under the summary receiver operating characteristic curve values of PB T-SPOT and CSF T-SPOT for TBM diagnosis were 0.83 (95% CI, 0.80–0.86) and 0.92 (95% CI, 0.89–0.94), respectively.Conclusions: CSF T-SPOT showed a higher specificity compared with PB T-SPOT for diagnosing TBM. Both two T-SPOT assays have considerable potential in improving the diagnosis of TBM. Furthermore, the standardization of the operating procedure is further needed when performing CSF T-SPOT.

Objective: 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 without testing in children younger than 5 years.

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Background: T-SPOT TB (T-SPOT) assay is widely used for detection of Mycobacterium tuberculosis infection that is based on the detection of M. tuberculosis -specific interferon-γ-secreting T cells (ISCs) in peripheral blood mononuclear cells (PBMCs). Recently, high frequencies of low-density granulocytes (LDGs) were found in the PBMCs of tuberculosis patients. Whether these LDGs affect the detection of T-SPOT has not been investigated. The impact of LDGs on T-SPOT assay and related mechanism were investigated in this study. Methods: The correlations between the frequencies of LDGs and the results of T-SPOT were analyzed. T-SPOT with LDG-removed PBMCs and PBMCs with exogenous addition of LDGs were performed. The possible mechanism was explored by detecting the levels of negative immune regulatory molecules on LDGs. The impact of programmed death ligand 1 (PD-L1) on T-SPOT was evaluated and confirmed by function blocking with neutralizing antibody. Results: The positive rates of T-SPOT and ISCs in tuberculosis patients with low LDGs frequency (n = 22) were significantly higher than those with high LDGs frequency (n = 39). Removal or exogenous addition of LDGs significantly increased or decreased the ISCs and the positive rate of T-SPOT. The frequencies of interferon-γ-producing T cells were negatively correlated with the frequencies of LDGs. The expression of PD-L1 was significantly elevated on LDGs. Pretreatment of LDGs with anti-PD-L1 antibody significantly counteracted the impact of LDGs on T-SPOT. Treatment of PBMCs with anti-PD-L1 antibody resulted in comparable ISCs with that of LDG removal. Conclusion: LDGs can inhibit the production of interferon-γ in T cells and decrease the positive rated of T-SPOT assay via highly expressed PD-L1. [ABSTRACT FROM AUTHOR]

Longitudinal studies regarding the reproducibility of Interferon-gamma release assay (IGRA) T-SPOT.TB for the diagnosis of Mycobacterium tuberculosis (M. tb) infection in serial testing are limited. We retrospectively analysed results of serially tested subjects in a medical laboratory in Germany over a time period of 14 years. From October 2004 to December 2018, a total of 5440 subjects were identified with a second T-SPOT.TB test after a median time interval of 258 days (interquartile range [IQR] 62–665). Consistently negative (n = 4520) or positive results (n = 682) were observed in 5202 (95.6%) subjects, indicating a high degree of concordance in serial testing (κ = 0.83). Test conversions occurred in 101 of 4621 (2.2%) subjects with initially negative tests. Of 819 subjects with initially positive test results, 137 (16.7%) had a test reversion which was associated with low spot numbers of the first test. Of 529 subjects retested within 1 year, only 60 (11.3%) displayed a test reversion. In subjects retested after more than 1 year, 77 of 290 (26.6%) tests reverted. This significantly higher rate of test reversions after more than 1 year was age-dependent and only observed in subjects above the age of 40 years. In the medical laboratory, the T-SPOT.TB test demonstrates a high reproducibility in serial testing. [ABSTRACT FROM AUTHOR]

Objective To explore the significance of T-SPOT.TB test for monitoring the therapeutic effect of tuberculosis. Methods Using T-SPOT.TB kit, changes in response to ESAT-6 and CFP-10 were compared in 79 patients with active pulmonary tuberculosis before and after 2 months of treatment. Results In 79 patients with active pulmonary tuberculosis,The spot number of ESAT-6 and CFP-10 responses decreased significantly at the end of 2 months and at the end of treatment compared with the beginning of treatment, and the difference was statistically significant(P < 0.05). The negative rates of ESAT-6 and CFP-10 at the end of 2 months and at the end of treatment were higher than those at the beginning of treatment, but there was no significant difference between them (P > 0.05). The T-SPOT.TB negative conversion rate of all patients was 3.8%.There was a statistical difference in ESAT-6 response between the end of 2 months and the end of treatment (χ² = 4.635,P = 0.031 < 0.05). There was no significant difference in CFP-10 response at the end of treatment 2 and at the end of treatment (χ2 = 1.272, P = 0.259 > 0.05). Conclusion There were significant differences in ESAT-6 and CFP-10 of T-SPOT.TB responses before and after treatment. T-SPOT has a certain significance in evaluating of the therapeutic effect of tuberculosis, but its negative conversion ration can not be used as the indicator of ending the TB treatment. [ABSTRACT FROM AUTHOR]

Background: The role of T-SPOT.TB (T-SPOT) assay for tuberculous meningitis (TBM) diagnosis has not been fully assessed. Here, we conducted an updated meta-analysis to evaluate the diagnostic accuracy of peripheral blood (PB) T-SPOT and cerebrospinal fluid (CSF) T-SPOT for diagnosing TBM. Methods: Relevant studies in the PubMed database, EmBase database, Cochrane database, Scopus database, Google Scholar, China National Knowledge Internet, and Wan-Fang database were retrieved from August 1, 2005, to June 22, 2020. Statistical analysis was performed using Stata, Revman, and Meta-Disc software. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), summary receiver operating characteristic curves, and the area under the curve were determined and analyzed. Results: A total of 27 studies were eligible for inclusion within the meta-analysis. The pooled sensitivity and specificity of PB T-SPOT for TBM diagnosis were 0.78 (95% CI, 0.76–0.81) and 0.68 (95% CI, 0.66–0.71), respectively, whereas the pooled PLR, NLR, and DOR were 2.80 (95% CI, 2.29–3.42), 0.32 (95% CI, 0.27–0.38), and 10.08 (95% CI, 7.21–14.08), respectively. On the other hand, the pooled sensitivity and specificity of CSF T-SPOT on diagnosing TBM were 0.76 (95% CI, 0.72–0.80) and 0.88 (95% CI, 0.85–0.90), respectively, whereas the pooled PLR, NLR, and DOR were 5.92 (95% CI, 4.25–8.25), 0.28 (95% CI, 0.21–0.39), and 29.05 (95% CI, 16.40–51.45), respectively. The area under the summary receiver operating characteristic curve values of PB T-SPOT and CSF T-SPOT for TBM diagnosis were 0.83 (95% CI, 0.80–0.86) and 0.92 (95% CI, 0.89–0.94), respectively. Conclusions: CSF T-SPOT showed a higher specificity compared with PB T-SPOT for diagnosing TBM. Both two T-SPOT assays have considerable potential in improving the diagnosis of TBM. Furthermore, the standardization of the operating procedure is further needed when performing CSF T-SPOT. [ABSTRACT FROM AUTHOR]