• Pediatric Infection and Vaccine
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• v.21 no.3
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• pp.191-198
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• 2014

Purpose: The aim of this study was to evaluate the clinical manifestations, contact history, and status of tuberculosis contact investigations in school-age children and adolescents with pulmonary tuberculosis (TB) at two centers. Methods: This study was conducted with 54 patients in the age ranging from 10 to 18 years, who were diagnosed with pulmonary TB at the Pusan National University Hospital and Pusan National University Children's Hospital, January 2008 to December 2012. We retrospectively reviewed the medical records of the patients. Results: The median age of the patients was 16 years old; 11 patients were aged 10 to 14 and 43 patients were aged 15 to 18. Among 54 patients, 19 had history of contact with pulmonary TB, 10 had contact with house members (household), and remaining 9 had contact with classmates (non-household). One out of 10 patients who had household contacts and 6 out of 9 patients who had non-household contacts were evaluated with contact investigation after the exposure to pulmonary TB. Among 7 patients who were evaluated with contact investigation, 3 were diagnosed with active pulmonary TB, 1 had latent tuberculosis infection (LTBI), and 3 had no evidence of TB or LTBI. The median period of diagnosis after the exposure to active pulmonary TB was 2 years in patients with household contacts and 0.23 years in patients with non-household contacts. Conclusion: This study suggested that if the contact investigation conducted properly, it would be helpful for early diagnosis and prevention of pulmonary TB.

• 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.26 no.2
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• pp.89-98
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• 2019

Purpose: Despite the decline in tuberculosis (TB) incidence and mortality rates in the Republic of Korea through a national TB control program, TB remains one of the most critical infectious diseases in Korean children. We investigated the trends and research areas of published articles on TB in Korean children and adolescents. Methods: In 6 Korean and overseas databases, we searched titles and abstracts including "tuberculo*" or "TB," "child*" or "adolescen*" or "neonat*" or "infant*" or "pediatric*," and "korea*." The publication type, publication year, research areas, journal title, and research subjects were analyzed. Results: Out of the 257 searched documents, 120 papers were included in the analysis. Of these, 82 were original articles (68.3%), 33 case reports (27.5%), 4 review articles (3.3%), and 1 guideline (0.8%). In the original articles, the most common subject of studies was the clinical characteristics of patients with TB (36.6%), followed by diagnostics (29.3%), contact investigations (9.8%), epidemiology (6.1%), treatment (4.9%), vaccine (3.6%), latent TB infection (3.6%), complications (3.6%), and surveys on perception of TB (2.4%). From 1962, 4 articles were published in the 1960s, 10 articles in the 1970s, 11 articles in the 1980s, 22 articles in the 1990s, 26 articles in the 2000s, and 47 articles since 2010. Conclusions: The amount of research on TB in Korean children has increased over the past 5 decades; however, it has mainly focused on the clinical characteristics and diagnostics. Research in different areas, such as treatment and vaccine, is needed in the future.

• Pediatric Infection and Vaccine
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• v.20 no.1
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• pp.17-27
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• 2013

Purpose: Recently, two tests are commercially available for the identification of latent tuberculosis infection (LTBI): tuberculin skin test (TST) and interferon-${\gamma}$ release assay (IGRA). Due to its false positiveness, TST tends to be preferred by IGRA until now. In our study, we simultaneously performed both TST and QuantiFERON$^{(R)}$-TB Gold In-Tube (QFT-GIT) and compared their results. Methods: TST and QFT-GIT were done for the diagnosis of LTBI among children who visited pediatric out-patient clinic at St. Vincent's Hospital, The Catholic University of Korea from February of 2007 to May of 2008. The study group was stratified into two groups in terms of whether there was intrafamilial contact or not. Results: Out of total 35 children, 29 were tuberculosis (TB)-exposed cases and the remainders were diagnosed as clinical pulmonary TB. Among these 29 children, TST was positive 38.9% (7/18) for the intrafamilial and 45.5% (5/11) for the nonintrafamilial, and at the same time, the result for QFT-GIT was positive 5.6% (1/18) and 9.1% (1/11), respectively which implies that TST was more sensitive than QFT-GIT. Among 29 TB-exposed cases, 26 initially went through TST and QFTGIT together on their first visit to out-patient clinic, and 15 continued the follow-up tests. Out of total 41 cases collected, the agreement (known as kappa value) was 0.063 which was relatively low. Including 6 cases with pulmonary TB who were all positive for TST and only 5 being positive for QFT-GIT, the final kappa value was 0.334. Conclusion: In our study, the agreement for TST and QFT-GIT was low, and the majorities were almost the cases of positive TST. In current situation with lacking a gold standard test and limited data on children to adolescents, this result is quite alarming that the recent trend tends to replace TST by QFT-GIT when diagnosing LTBI.

• Tuberculosis and Respiratory Diseases
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• v.59 no.4
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• pp.406-412
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• 2005

Background : Recently, two commercialized whole-blood assays, $QuantiFERON^{(R)}-TB$ Gold (QFT) and T $SPOT-TB^{(R)}$ (SPOT), which measure the $IFN-{\gamma}$ released in the whole blood after being incubation with mycobacterial antigens, were approved for the diagnosis of a latent tuberculosis infection (LTBI). However, there is data on whether or not the previously used PPD skin tests (TST) have any influence on the diagnostic ability of these ex-vivo $IFN-{\gamma}$ assays. Methods : Forty-six 15 year-old students who did not appear to be infected with Mycobacterium tuberculosis were enrolled in this study. The peripheral blood was collected and used for two $IFN-{\gamma}$ assays. The $IFN-{\gamma}$ assays and TST were performed at the baseline ($1^{st}$). The TST was repeated two months later ($2^{nd}$), and the $IFN-{\gamma}$ assays were repeated two ($2^{nd}$) and four months ($3^{rd}$) later only in those subjects who had negative results at the baseline in both the $IFN-{\gamma}$ assays and TST. An induration size > 10 mm was considered to be positive in the TST. Results : The mean TST value was $3.1{\pm}5.4mm$ (range: 0-20). Of the 46 subjects examined, 13 subjects (28.3%) showed positive results in the two-step TST. Nine (19.6%) were SPOT-positive and only one (2.2%) was QFT-positive. The $2^{nd}$ and $3^{rd}$ QFT were carried out in 23 and 25 all-negative subjects, respectively, and all showed negative results. The $2^{nd}$ SPOT was performed in 23 subjects and only one (4.3%) showed a weak-positive result. Conclusion : Even though there were some discrepancies in the results of the two ex-vivo $IFN-{\gamma}$ assays, it appears that their results were not influenced by a previous TST carried out in two or four months earlier.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.30 no.1
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• pp.67-74
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• 2020

Objectives: Previous study has shown that the positive rate of latent tuberculosis infection(LTBI) among former workers in dusty environments was higher than that among high-risk groups of tuberculosis(TB). The objective of the present study was to identify the development of active TB among former workers in dusty environments diagnosed with LTBI. Methods: Between January 2015 and May 2017, 796 former workers in dusty environments who had been subjects of epidemiology research for work-related chronic obstructive pulmonary disease(COPD) had received the QuantiFERON-TB® Gold In-Tube(QFT-GIT) from the Institute of Occupation and Environment(IOE) under the Korea Workers' Compensation and Welfare Service(KCOMWEL). Among them, 437 participants who received a health examination for work-related pneumoconiosis between January 2015 and December 2018 were selected as study subjects. Active TB was defined as a positive result for active PTB and non-tuberculosis mycobacteria infection in the result of the Pneumoconiosis Examination Council's assessment by KCOMWEL. Results: A total of 437 subjects were followed up for 2.1 years. Four of them(4/437, 0.9%) developed active TB during the follow-up period. The attack rate of active TB among subjects who were diagnosed LTBI positive and those who were diagnosed LTBI negative were 0.9%(3/320) and 0.9%(1/115), respectively. Conclusions: Most previous studies reported that the attack rate of the development of active TB in subjects who had been diagnosed LTBI positive was higher than that among subjects who had been diagnosed LTBI negative. To the contrary, the present study found that the rate of developing active TB among former workers in dusty environments diagnosed as LTBI positive was not higher than that in those who were diagnosed LTBI negative.

• 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.

• 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.66 no.1
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• pp.13-19
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• 2009

Background: The interferon-gamma assay is reported to have high sensitivity and specificity for making the diagnosis of latent tuberculosis infection. The clinical usefulness of this essay for detecting active tuberculosis has not fully defined. We evaluated the diagnostic value of the commercial interferon-gamma assay kit (QuantiFERONTB GOLD) for patients with suspected tuberculosis. Methods: From January to August 2007, we recruited 52 patients with suspected tuberculosis infection. We performed chest X-ray, sputum smear, culture, PCR and the QuantiFERON-TB GOLD test. Pleural fluid analysis and pleural biopsy were also done for the patients with pleural effusion. Results: Of the 52 patients we studied, 30 patients had a positive QuantiFERON-TB GOLD test result. 35 patients were finally diagnosed with active tuberculosis: twenty-five with a positive QuantiFERON-TB GOLD test and 10 with a negative QuantiFERON-TB GOLD test. The sensitivity of the QuantiFERON-TB GOLD test was 71.4% and the specificity was 64.7%. The positive predictive value was 0.83 and the negative predictive value was 0.50. There was no significant difference of any of the clinical and laboratory characteristics between the two groups of patients except the C-reactive protein (CRP) level. The CRP level was 29.2${\pm}$27.3 mg/dL in the pulmonary tuberculosis patients with a positive QuantiFERON-TB GOLD test and 72.9${\pm}$67.9 mg/dL in the patients with a negative QuantiFERON-TB GOLD test (p<0.05). Conclusion: The sensitivity and specificity of the QuantiFERON-TB GOLD test were inadequate for making the diagnosis of active tuberculosis. We suggest that the QuantiFERON-TB GOLD test should not be used by itself to exclude the diagnosis of active tuberculosis. The relationship of the QuantiFERON-TB GOLD test and the CRP level in patients with TB would be further investigated.

• 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.