• Clinical and Experimental Pediatrics
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• v.59 no.6
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• pp.256-261
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• 2016

Purpose: Latent tuberculosis infection (LTBI) in young children may progress to severe active tuberculosis (TB) disease and serve as a reservoir for future transmission of TB disease. There are limited data on interferon-${\gamma}$ release assay (IGRA) performance in young children, which our research aims to address by investigating the usefulness of IGRA for the diagnosis of LTBI. Methods: We performed a tuberculin skin test (TST) and IGRA on children who were younger than 18 years and were admitted to Chung-Ang University Hospital during May 2011-June 2015. Blood samples for IGRA were collected, processed, and interpreted according to manufacturer protocol. Results: Among 149 children, 31 (20.8%) and 10 (6.7%) were diagnosed with LTBI and active pulmonary TB, respectively. In subjects lacking contact history with active TB patients, TST and IGRA results were positive in 41.4% (29 of 70) and 12.9% (9 of 70) subjects, respectively. The agreement (kappa) of TST and IGRA was 0.123. The control group, consisting of non-TB-infected subjects, showed no correlation between age and changes in interferon-${\gamma}$ concentration after nil antigen, TB-specific antigen, or mitogen stimulation in IGRAs (P=0.384, P=0.176, and P=0.077, respectively). In serial IGRAs, interferon-${\gamma}$ response to TB antigen increased in IGRA-positive LTBI subjects, but did not change considerably in initially IGRA-negative LTBI or control subjects. Conclusion: The lack of decrease in interferon-${\gamma}$ response in young children indicates that IGRA could be considered for this age group. Serial IGRA tests might accurately diagnose LTBI in children lacking contact history with active TB patients.

• Biomedical Science Letters
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• v.24 no.2
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• pp.138-142
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• 2018

The incidence of tuberculosis (TB) in the Republic of Korea remains high when compared to the incidence in other Organization for Economic Cooperation and Development (OECD) countries. The prompt diagnosis and effective treatment of latent TB infection (LTBI) are very important in terms of controlling the burden of TB. The tuberculin skin test (TST) has long been the "gold standard" assay for the diagnosis of LTBI. However, it can show false positive results due to Bacille Calmette-$Gu{\acute{e}}rin$ (BCG) vaccination and infection with many environmental nontuberculous mycobacteria (NTM). The interferon gamma release assay (IGRA) using Mycobacterium tuberculosis (MTB)-specific antigens, was developed for the detection of LTBI. The QuantiFERON-TB Gold In-Tube assay is one of the most commonly used forms of the IGRA. In order to compare the diagnostic efficacy of the TST and IGRA in relation to LTBI among BCG-vaccinated healthy donors, whole blood samples were collected from 51 participants, and the results of the TST and IGRA were compared. Of the 51 cases, 18 cases (35.3%) were positive and 33 cases (64.7%) were negative when using the TST, while four cases (7.8%) were positive and 47 cases (92.2%) negative when using the IGRA. There was no correlation between the size of the induration in the TST and the $IFN-{\gamma}$ protein level. In conclusion, the TST showed higher cross-reactivity among the BCG-vaccinated healthy participants, therefore, the IGRA might be the most suitable assay for the rapid screening of LTBI in BCG-vaccinated healthy population, or for TB contact investigation.

• Journal of Preventive Medicine and Public Health
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• v.52 no.4
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• pp.272-275
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• 2019

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-$Gu{\acute{e}}rin$ 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.

• Tuberculosis and Respiratory Diseases
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• v.68 no.3
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• pp.155-161
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• 2010

Background: The tuberculin skin test (TST) has limitations in diagnosing a latent tuberculosis infection (LTBI). The interferon-gamma release assay (IGRA) was introduced to middle- and high-school students since 2009 by the Korea Centers for Disease Control and Prevention. The aim was to evaluate the utility of IGRA in diagnosing LTBI in middle- and high-school students. Methods: From August 2007 to July 2009, among suspected LTBI students showing TST induration with a 10 mm diameter and over with a normal chest x-ray in school students of Jeju city, 341 students underwent a Quanti FERON-TB Gold In-Tube (QFT-IT) test to confirm LTBI. Results: From 348 students showing a positive TST, a QFT-IT test was carried out on 341 students. The positive QFT-IT rate was 52.8% (=180/341). The positive QFT-IT rate was higher in high-school boys with a 15~19 mm diameter of induration in TST. Conclusion: With the introduction of IGRA for diagnosing LTBI in middle- and high-school students, approximately 47% of students who show a TST induration with a 10 mm diameter and over can avoid taking unnecessary preventive chemotherapy. These results suggest that IGRA is useful for diagnosing and controlling LTBI in Korean students.

• Korean Journal of Clinical Laboratory Science
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• v.48 no.3
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• pp.225-229
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• 2016

Tuberculosis (TB) is caused by a chronic infectious agent known as Mycobacterium tuberculosis. It is transmitted in airborne particles, called droplet nuclei which was generated by cough, sneeze, shout, or sing of persons who have TB disease. Most infections of TB do not have symptoms, well known as latent tuberculosis infection (LTBI). However, about 10% of LTBI progress to active disease a one or two years after infection. To investigate the LTBI rate of college students who were in contacted with TB patients, we performed chest X-ray, tuberculin skin test (TST) and Interferon-gamma release assay (IGRA) to 74 college students. At a results, 65 students were showed negative and 9 students positive results at chest X-ray and 1st TST test. When confirmed the 65 students who were showed negative by 2st TST, the results showed correctly. But, 9 students who were showed positive results on chest X-ray and 1st TST by IGRA, the only 3 students (4.05%) showed positive results. In conclusion, the LTBI rate in this study showed 4.05% (3/74) and we suggest to investigate other students LTBI rate for decreasing tuberculosis.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.27 no.3
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• pp.238-244
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• 2017

Objectives: The major objective of this study was to investigate the prevalence of and risk factors for latent tuberculosis infection (LTBI) among employees at a workers' compensation hospital. Methods: Among the 394 employees at Incheon Hospital, 362 were enrolled in the study. An interferon-gamma release assay(IGRA) for diagnosis of LTBI was performed using QuantiFERON$^{(R)}$ TB Gold In-Tube(QFT-IT). Risk factors for LTBI were analyzed using logistic regression analysis. Results: The overall prevalence of LTBI was 32.0%(116/362). The non-medical departments have a significantly high prevalence compared to medical departments(39.7% vs 23.2%). In multivariate logistic regression analysis, experience working in the pneumoconiosis hospital(OR, 3.6; 95% CI, 1.3-10.3) was associated with development of LTBI. Conclusions: Korean guidelines for the management of tuberculosis recommend annual regular health examinations for TB and LTBI for health care workers(HCWs). Considering the high prevalence of and risk factors for LTBI among non-HCWs, it suggests a need for annual regular health examinations for TB and LTBI for all employees at workers' compensation hospitals, including pneumoconiosis hospitals.

• Tuberculosis and Respiratory Diseases
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• v.83 no.4
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• pp.283-288
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• 2020

Background: Latent tuberculosis (TB) infection among TB contacts is diagnosed using plain chest radiography and interferon-gamma release assays (IGRAs). However, plain chest radiographs often miss active TB, and the results of IGRA could fluctuate over time. The purpose of this study was to elucidate changes in the results of the serial IGRAs and in the findings of the serial submillisievert chest computed tomography (CT) scans among the close contacts of active pulmonary TB patients. Methods: Patients age 20 or older with active pulmonary TB and their close contacts were invited to participate in this study. Two types of IGRA (QuantiFERON-TB Gold In-Tube assay [QFT-GIT] and the T-SPOT.TB test [T-SPOT]) and submillisievert chest CT scanning were performed at baseline and at 3 and 12 months after enrollment. Results: In total, 19 close contacts participated in this study. One was diagnosed with active pulmonary TB and was excluded from further analysis. At baseline, four of 18 contacts (22.2%) showed positive results for QFT-GIT and T-SPOT; there were no discordant results. During the follow-up, transient and permanent positive or negative conversions and discordant results between the two types of IGRAs were observed in some patients. Among the 17 contacts who underwent submillisievert chest CT scanning, calcified nodules were identified in seven (41.2%), noncalcified nodules in 14 (82.4%), and bronchiectasis in four (23.5%). Some nodules disappeared over time. Conclusion: The results of the QFT-GIT and T-SPOT assays and the CT images may change during 1 year of observation of close contacts of the active TB patients.

• Pediatric Infection and Vaccine
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• v.23 no.1
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• pp.18-24
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• 2016

Purpose: There is a the great diagnostic challenge in pediatric tuberculosis especially in high burden setting. The purpose of this preliminary study is to evaluate the agreement between tuberculin skin test (TST) and interferon-gamma release assay (IGRA) including T-SPOT$^{(R)}$.TB and QuantiFERON$^{(R)}$-TB Gold (QFT-G) in Korean children. Method: This retrospective study included children and adolescents who visited to Asan Medical Center to evaluate tuberculosis infection using at least two assays of TST, T-SPOT.TB and QFT-G, from January 2014 to April 2015. Results: A total of 20 patients were included, whose median age was 13.3 years (range, 3.8-18.1 years), and all of them had history of BCG vaccination. Eleven patients had underlying diseases including 7 patients with immunosuppressant medication. The concordance rate between T-SPOT.TB and QFT-G was 90%. However, the concordance rate between TST and T-SPOT.TB was 50%, and between TST and QFT-G was 42.9%. Specificity for the diagnosis of tuberculosis infection of T-SPOT.TB, QFT-G, and TST was 93.3%, 86.7%, and 58.3%, respectively. Conclusions: Although there was a discrepancy between TST and IGRA to diagnose tuberculosis, agreement between T-SPOT.TB and QFT-G was relatively high. Further prospective study to validate the clinical usefulness of each assay for immunologic evidence of tuberculosis infection in Korean children will be mandatory.

• Pediatric Infection and Vaccine
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• v.18 no.1
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• pp.48-53
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• 2011

Purpose : Early diagnosis of active tuberculosis (TB) in children is difficult. The widely used tuberculin skin test has low sensitivity and cross reactivity with non-tuberculous mycobacteria or Bacille Calmette-Gu$\acute{e}$rin vaccination. Interferon gamma release assays have been shown good diagnostic accuracy for active in adults. But studies in children were limited. The purpose of this study was to examine the performance of enzyme-linked immunospot assay (ELISpot) as an initial test in the diagnosis of active tuberculosis in children. Methods : In a hospital-based study, we prospectively examined the performance of ELISPot in 33 children suspected of active TB. TB was confirmed bacteriologically or histologically. Results : Among 33 patients, 9 had active tuberculosis. When tested, they all had a positive test result from the ELISpot. The sensitivity and specificity of the assay were 100% (95% CI, 66.4-100%) and 95.8% (95% CI, 78.9-99.9%) respectively. Conclusion : ELISpot might be an useful and improved clinical diagnostic method for the detection of active TB in children.

• Health Policy and Management
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• v.23 no.4
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• pp.349-357
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• 2013

Background: Although interferon-gamma release assay (IGRA) is now available alternatives to tuberculin skin test (TST) for detection of latent tuberculosis infection (LTBI), the cost of IGRA test is much higher than TST. So economic analysis of LTBI screening strategies have been done in many countries, but there are few reports in Korea. This study examined cost analysis of LTBI screening strategies in Korea. Methods: The economic outcomes were evaluated by five strategies. These were 1) TST alone, 2) IGRA alone, 3) combination of TST and IGRA (TST followed by IGRA) and 4) no testing no prevention, 5) no testing all prevention. Last two strategies were added to compare with three main LTBI screening strategies. Decision analysis model were used to perform economic analysis. A cohort study of Korean Institute of Tuberculosis and the data of published literatures were used to estimate the cost analysis. Results: In a base-case scenario which was assumed that TST specificity was 80%, TST alone was the least expensive strategy. In a alternative scenario which was assumed that TST specificity was 97%, the combination of TST and IGRA was the least expensive strategy. Sensitivity analysis shows that patients adherent rate to LTBI treatment, TST sensitivity, IGRA sensitivity and IGRA specificity did not have a significant impact on the outcomes. Conclusion: In Korea, for the diagnosis of LTBI at the time of child and adolescent, TST alone reduces medical costs compared with IGRA alone or combination of TST and IGRA.