Objective The aim of this study was to evaluate the diagnostic performance of T-SPOT.TB for tuberculous lymphadenitis. Methods Suspected tuberculous lymphadenitis patients between September 2010 and September 2018 who had both peripheral blood T-SPOT.TB test and lymph node biopsy were retrospectively enrolled in this study. The cutoff value of T-SPOT.TB test for peripheral blood was set as 24 spot forming cell (SFC)/10 ⁶ periphreral blood monocyte cell (PBMC) according to the instruction of testing kits. The gold standard for diagnosis of TBL was the combination of microbiology results, histopathology results and patient's response to anti-TB treatment. Diagnostic efficacy of T-SPOT.TB was evaluated, including sensitivity, specificity, accuracy, predictive values, and likelihood ratio. Results Among 91 patients who met the inclusion criteria, we excluded 8 cases with incomplete clinical information and 6 cases who lost to follow-up. According to the gold standard, there were 37 cases of true TBL (9 confirmed TBL and 28 probable TBL), 30 cases of non-TBL, and 10 cases of clinically indeterminate diagnosis who were excluded from the final analyses. The T-SPOT.TB tests yielded 43 cases of positive response and 24 cases of negative response. The sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of peripheral blood T-SPOT.TB for diagnosing TBL were 89.2%, 66.7%, 79.1%, 76.7%, 83.3%, 2.68 and 0.16, respectively. The number of SFCs of T-SPOT.TB in TBL patients [432(134-1264)/10 ⁶ PBMCs] was higher than that in non-TBL patients [0 (0-30) /10 ⁶PBMCs] with a significant difference (Z=-5.306, P <0.001). Conclusion T-SPOT.TB is a rapid and simple diagnostic test for TBL with a high sensitivity and negative predictive value.
Adolescent ; Adult ; Aged ; Female ; Humans ; Interferon-gamma Release Tests ; Male ; Middle Aged ; Mycobacterium tuberculosis/physiology* ; T-Lymphocytes/immunology* ; Tuberculosis, Lymph Node/diagnosis* ; Young Adult

BACKGROUND: As stated in ‘The Action Strategy for Tuberculosis-Free Korea,’ last March, high-throughput, large-scale analytical instruments for interferon gamma release assays (IGRA) are demanded by many clinical laboratories using the QuantiFERON-TB Gold In-Tube assay (Cellestis/Qiagen, Australia). Agility (Dynex Technologies, USA) is an automated high-throughput enzyme linked immunosorbent assay analyser. The present study aimed to evaluate its accuracy and speed. METHODS: Pooled plasma was prepared using samples obtained after IGRA testing. Analyses of precision, linearity, cut-off evaluation, and comparison with conventional methods were performed for multiple Agility instruments according to the Clinical and Laboratory Standards Institute EP5-A3, EP6-A, EP9-A3 and EP12-A2 guidelines. The turnaround time and throughput were also analysed. RESULTS: The coefficient of variation range was 2.48%–4.0%, 7.01%–11.17%, and 9.69%–14.84% for the repeatability, between-run precision, and between-day precision analyses, respectively. The linearity ranged from 0 to 10.541. Comparison analysis presented a high concordance of Agility with the conventional instrument, DS2 (Dynex Technologies), and manual method for IGRA. The cut-off value of 0.35 IU/mL was well compatible with the C50. It was identified that the C50±20% contained the C5–C95 interval. The average turnaround time was 3.84 hours, from the submission of pre-treated samples to the reporting of results. The throughput was determined to be 290 tests during a routine working time of 8 hours. CONCLUSIONS: Agility showed high precision, linearity, concordance, and had a 2.5 times faster throughput than with the conventional and manual method. It could be useful for large-scale IGRA testing in latent tuberculosis infection screening project. Samples within C50±20% are suspected to show relatively low reporducible results of high inversion between postivie and negative.
Enzyme-Linked Immunosorbent Assay ; Interferon-gamma Release Tests ; Interferons ; Latent Tuberculosis ; Mass Screening ; Methods ; Plasma

PURPOSE: The purpose of this study was to provide basic data on the infection prevention management program, which is one of the infectious disease control program by identifying the prevalence and risk factors of latent tuberculosis infection (LTBI) in healthcare workers.METHODS: We surveyed a total of 3,046 LTBI test results, including those of 2,269 existing staff and 777 new employees. An interferon-gamma release assay (IGRA) for the diagnosis of LTBI was performed using QuantiFERON®-TB Gold In-Tube (QFT-IT). The risk factors of LTBI were analyzed using logistic regression analysis.RESULTS: The overall prevalence of LTBI was 16.0% (487/3,046). The prevalence of LTBI in the existing staff was 17.9% (406/2,269) and the prevalence of LTBI in new employees was 10.4% (81/777). Multivariate logistic regression analysis revealed that the risk factors of latent tuberculosis infection among the existing staff were gender, age and work period wheres, the risk factor amongst the new employees depended on their age.CONCLUSION: The LTBI was not related to the type of occupation and work unit. Therefore, while establishing an infection control program for the prevention of tuberculosis infection at medical institurions, institutional heads and infection control experts should encompass a policy for all the employees.
Communicable Diseases ; Delivery of Health Care ; Diagnosis ; Head ; Infection Control ; Interferon-gamma Release Tests ; Latent Tuberculosis ; Logistic Models ; Occupations ; Prevalence ; Risk Factors ; Tuberculosis

BACKGROUND: Tuberculosis (TB) is increasing in immigrants. We aimed to investigate the current status of latent tuberculosis infection (LTBI) treatment for North Korean Refugees (NKR) compared to South Koreans Contacts (SKC). METHODS: TB close contacts in a closed facility of SKC and NKR who underwent LTBI screening in a settlement support center for NKR were analyzed retrospectively. RESULTS: Among tuberculin skin test (TST) ≥10 mm (n=298) reactors, the males accounted for 72.2% in SKC (n=126) and 19.5% in NKR (n=172) (p<0.01). The mean age was higher in South Korea (42.8±9.9 years vs. 35.4±10.0 years, p<0.01). Additionally, the mean TST size was significantly bigger in NKR (17.39±3.9 mm vs. 16.57±4.2 mm, p=0.03). The LTBI treatments were initiated for all screened NKR, and LTBI completion rate was only 68.0%. However, in NKR, LTBI treatment completion rate was significantly increased by shorter 4R regimen (odds ratio [OR], 9.296; 95% confidence interval [CI], 4.159–20.774; p<0.01) and male (OR, 3.447; 95% CI, 1.191–9.974; p=0.02). CONCLUSION: LTBI treatment compliance must be improved in NKR with a shorter regimen. In addition, a larger study regarding a focus on LTBI with easy access to related data for NKR should be conducted.
Asian Continental Ancestry Group ; Compliance ; Emigrants and Immigrants ; Humans ; Interferon-gamma Release Tests ; Korea ; Latent Tuberculosis ; Male ; Mass Screening ; Refugees ; Retrospective Studies ; Skin Tests ; Tuberculin ; Tuberculin Test ; Tuberculosis

BACKGROUND: Latent tuberculosis infection is a condition where there is a persistent immune response to Mycobacterium tuberculosis without clinical manifestations of tuberculosis. Currently, there is no gold standard to diagnose latent tuberculosis infection. The tuberculin skin test and interferon-gamma release assay are currently used to diagnose latent tuberculosis infection. However, studies have shown inconsistencies regarding the level of agreement between these tests in different settings. In this study, we aimed to evaluate the agreement between these two tests for diagnosing latent tuberculosis infection in human immunodeficiency virus (HIV)-infected individuals. METHODS: We screened HIV patients with no clinical symptoms of tuberculosis, a normal chest X-ray, and no history of tuberculosis or use of antituberculous drugs. Participants were tested with tuberculin skin test (TST) and T-SPOT.TB (an interferon gamma release assay) simultaneously. Participants' HIV stage was determined by measuring the level of CD4+ T-lymphocytes. Tuberculosis status was confirmed by sputum examination using GeneXpert. The level of agreement between the TST and T-SPOT.TB results was measured using Cohen's κ coefficient. RESULTS: Of the 112 participants, 20 had a positive T-SPOT.TB test result, and 21 had a positive TST result. The TST and T-SPOT.TB test results showed a high level of agreement (κ = 0.648, P < 0.001). Performance of the tests did not vary with CD4+ level. However, in participants with CD4+ < 200 cells/mm³, T-SPOT.TB detected more latent tuberculosis infections than the TST. CONCLUSION: There was good agreement between the TST and T-SPOT.TB results of latent tuberculosis infection in participants. TST is the preferred test for diagnosing latent tuberculosis infection in HIV-infected patients, especially in resource-limited settings, because it is simple and cost-effective. However, T-SPOT.TB may be useful to rule out latent tuberculosis infection in patients with severe immunodeficiency.
HIV ; Humans ; Indonesia ; Interferon-gamma Release Tests ; Interferons ; Latent Tuberculosis ; Mycobacterium tuberculosis ; Skin Tests ; Skin ; Sputum ; T-Lymphocytes ; Thorax ; Tuberculin ; Tuberculosis

The 2018 National Guideline for Tuberculosis Control, which was published by the Korea Centers for Diseases Prevention and Control (KCDC), mandates conducting an epidemiological survey among close contacts of active tuberculosis patients at public institutions such as schools. In the procedure for these surveys, the tuberculin skin test (TST) is mandated as the screening test for latent tuberculosis infection in elementary school students. However, several guidelines recommend using the interferon-gamma releasing assay (IGRA) for contacts aged over 5 years with a Bacillus Calmette–Guérin vaccination history. The main reason for this is that IGRA has a higher specificity and lower false positive rate than TST. In addition, IGRA requires only a single visit to draw blood and the results are available within 24 hours. These advantages could promote cooperation from both parents and students in conducting these surveys. Thus, these findings regarding the benefits of IGRA for surveys of close contacts at elementary schools should be incorporated into the KCDC guideline.
Bacillus ; Humans ; Interferon-gamma ; Interferon-gamma Release Tests ; Korea ; Latent Tuberculosis ; Mass Screening ; Mycobacterium tuberculosis ; Parents ; Sensitivity and Specificity ; Skin Tests ; Tuberculin ; Tuberculin Test ; Tuberculosis ; Vaccination

In order to eliminate tuberculosis worldwide by 2050, effective management of latent tuberculosis infection is essential, and policy-makers have begun to recognize the importance of scaling up preventive therapy. The current guideline recommends targeted latent tuberculosis infection testing that identifies high-risk groups based on risk stratification for progression from latent infection to active disease. Both the tuberculin skin test and interferon-gamma releasing assay have a similar diagnostic efficacy for predicting progression to active tuberculosis. The Korean guideline recommends 9-month isoniazid monotherapy as the standard treatment; however, more evidence supports that short course rifampicin-based regimen is both more effective and tolerable than isoniazid monotherapy.
Diagnosis ; Interferon-gamma ; Interferon-gamma Release Tests ; Isoniazid ; Latent Tuberculosis ; Skin Tests ; Tuberculin ; Tuberculosis

BACKGROUND/AIMS: The data on the risk of tuberculosis (TB) reactivation with infliximab (IFX) in patients with inflammatory bowel disease (IBD) from TB endemic countries, like India, is limited. The risk of TB reactivation on IFX and its predictors in patients with IBD was assessed. METHODS: This retrospective review included consecutive patients with IBD who received IFX, and were on follow-up from January 2005 to November 2017. The data was recorded on age/disease duration, indications for IFX, screening for latent tuberculosis (LTB) before IFX, response to IFX, incidence and duration when TB developed after IFX, and type of TB (pulmonary [PTB]/extra-pulmonary [EPTB]/disseminated). RESULTS: Of 69 patients (22 ulcerative colitis/47 Crohn’s disease; mean age, 35.6±14.5 years; 50.7% males; median follow-up duration after IFX, 19 months [interquartile range, 5.5–48.7 months]), primary non-response at 8 weeks and secondary loss of response at 26 and 52 weeks were seen in 14.5%, 6% and 15% patients respectively. Prior to IFX, all patients were screened for LTB, 8 (11.6%) developed active TB (disseminated, 62.5%; EPTB, 25%; PTB, 12.5%) after a median of 19 weeks (interquartile range, 14.0–84.5 weeks) of IFX. Of these 8 patients’ none had LTB, even when 7 of 8 were additionally screened with contrast-enhanced chest tomography. Though not statistically significant, more patients with Crohn’s disease than ulcerative colitis (14.9% vs. 4.5%, P=0.21), and those with past history of TB (25% vs. 9.8%, P=0.21), developed TB. Age, gender, disease duration, or extraintestinal manifestations could not predict TB reactivation. CONCLUSIONS: There is an extremely high rate of TB with IFX in Indian patients with IBD. Current screening techniques are ineffective and it is difficult to predict TB after IFX.
Colitis, Ulcerative ; Crohn Disease ; Follow-Up Studies ; Humans ; Incidence ; India* ; Inflammatory Bowel Diseases* ; Infliximab* ; Interferon-gamma Release Tests ; Latent Tuberculosis ; Male ; Mass Screening* ; Retrospective Studies ; Thorax ; Tuberculosis* ; Ulcer

BACKGROUND/AIMS: To estimate the level of agreement and positivity rates of latent tuberculosis infection (LTBI) tests prior to the use of tumor necrosis factor (TNF) inhibitors in relation to underlying rheumatic diseases and endemic tuberculosis levels. METHODS: The Ovid-Medline, Embase, and Cochrane Libraries were searched for articles before October 2013 involving LTBI screening in rheumatic patients, including rheumatoid arthritis (RA), ankylosing spondylitis (AS), juvenile idiopathic arthritis (JIA), and psoriatic arthritis. RESULTS: In pooled analyses, 5,224 rheumatic patients had undergone both a tuberculin skin test (TST) and an interferon-gamma release assay (IGRA) before TNF inhibitors use. The positivity of TST, QuantiFERON-TB Gold In Tube (QFT-GIT), and T-SPOT.TB (T-SPOT) tests were estimated to be 29%, 17%, and 18%, respectively. The agreement percentage between the TST and QFT-GIT, and between the TST and T-SPOT were 73% and 75%. Populations from low-to-moderate endemic TB presented with slightly less agreement (71% between TST and QFT-GIT, and 74% between TST and T-SPOT) than patients from high endemic countries (73% between TST and QFT-GIT, and 81% between TST and T-SPOT). By underlying disease stratification, a lower level of agreement between TST and QFT-GIT was found among AS (64%) than among JIA (77%) and RA patients (73%). CONCLUSIONS: We reaffirm the current evidence for accuracy of LTBI test done by TST and IGRA among rheumatic patients is inconsistent. Our stratified analysis suggests different screening strategies might be needed in clinical settings considering the endemic status in the patient’s country of origin and the precise nature of underlying diseases.
Arthritis, Juvenile ; Arthritis, Psoriatic ; Arthritis, Rheumatoid ; Humans ; Interferon-gamma Release Tests ; Latent Tuberculosis* ; Mass Screening* ; Rheumatic Diseases* ; Skin Tests ; Spondylitis, Ankylosing ; Tuberculin ; Tuberculin Test ; Tuberculosis ; Tumor Necrosis Factor-alpha

BACKGROUND: We investigated the incidence of active tuberculosis among patients with inflammatory bowel disease (IBD) treated with tumor necrosis factor (TNF) inhibitors, with or without latent tuberculosis infection (LTBI). METHODS: The study was performed at a Korean tertiary referral center between January 2011 and June 2017. In total, 740 patients with IBD who underwent LTBI screening tests and were followed-up for ≥ 1 year after TNF inhibitor treatment initiation were enrolled. LTBI was detected on the basis of tuberculin skin test results, interferon-gamma release assay results, chest X-ray findings, and previous tuberculosis treatment history. The patients were classified into LTBI (n = 84) or non-LTBI (n = 656) group. The risk of developing tuberculosis in each group was assessed on the basis of standardized incidence ratio (SIR) and 95% confidence interval (CI) for active tuberculosis. RESULTS: Mean patient age was 33.1 years, and patients with Crohn's disease were predominant (80.7%). Within 1 year after the initiation of TNF inhibitor treatment, 1 patient in the LTBI group (1/84; 1.2%) and 7 patients in the non-LTBI group (7/656; 1.1%) developed active tuberculosis. The overall 1-year incidence of tuberculosis among the patients was significantly higher than that among the general population (SIR, 14.0; 95% CI, 7.0–28.0), and SIR was not affected by LTBI status (LTBI group: 14.5, 95% CI, 2.0–102.6; non-LTBI group: 14.0, 95% CI, 6.7–29.4). CONCLUSION: Patients with IBD undergoing TNF inhibitor treatment showed a higher 1-year incidence of tuberculosis than the general population irrespective of LTBI status.
Crohn Disease ; Humans ; Incidence* ; Inflammatory Bowel Diseases* ; Interferon-gamma Release Tests ; Latent Tuberculosis* ; Mass Screening ; Skin Tests ; Tertiary Care Centers ; Thorax ; Tuberculin ; Tuberculosis* ; Tumor Necrosis Factor-alpha*