• Tuberculosis and Respiratory Diseases
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• v.86 no.2
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• pp.94-101
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• 2023

A recent understanding of the dynamic continuous spectrum of Mycobacterium tuberculosis infection has led to the recognition of incipient tuberculosis, which refers to the latent infection state that has begun to progress to active tuberculosis. The importance of early detection of these individuals with a high-risk of progression to active tuberculosis is emphasized to efficiently implement targeted tuberculosis preventive therapy. However, the tuberculin skin test or interferon-γ release assay, which is currently used for the diagnosis of latent tuberculosis infection, does not aid in the prediction of the risk of progression to active tuberculosis. Thus, a novel test is urgently needed. Recently, simultaneous and systematic analysis of differentially expressed genes using a high-throughput platform has enabled the discovery of key genes that may serve potential biomarkers for the diagnosis or prognosis of diseases. This host transcriptional investigation has been extended to the field of tuberculosis, providing promising results. The present review focuses on recent progress and challenges in the field of blood transcriptional signatures to predict progression to active tuberculosis.

• 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.

• Pediatric Infection and Vaccine
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• v.18 no.1
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• pp.1-14
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• 2011

Tuberculosis is a disease with high morbidity and mortality in children worldwide. Despite the decrease in the incidence of tuberculosis in Korea, more than 30,000 new patients are diagnosed each year. Active tuberculosis is less frequent in children compared to adults but the risk of miliary tuberculosis and CNS tuberculosis is much higher. The diagnosis of tuberculosis in children and adolescents is difficult due to the nonspecific symptoms upon presentation. Diagnostic work up is based on the confirmation of tuberculosis infection by tuberculin skin test, abnormal radiologic findings, and contact with an adult with active tuberculosis. Anti-tuberculosis medications are prescribed according to the drug susceptibility of the index patient. Latent tuberculosis infection plays an important role in adult tuberculosis by reactivation. Thus, it is critical to accurately diagnose latent tuberculosis in children to prevent reactivation in adulthood. Korean guidelines for diagnosis and treatment of tuberculosis in children and adolescents provide evidence based recommendations in the optimal diagnosis and treatment for active and latent tuberculosis in children and adolescents based on the current Korean situation.

• Tuberculosis and Respiratory Diseases
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• v.82 no.3
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• pp.194-200
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• 2019

Background: Tuberculosis (TB) is a major infectious disease in South Korea causing substantial disease burden, particularly in the elderly. This study aimed to identify the case detection rate of mobile TB screening for the elderly conducted in the Jeollanam-do region and to analyze risk factors of active TB. Methods: We screened the elderly population (${\geq}65$ years old) in Jeollanam-do from August to December 2017. Chest radiography was performed for all participants. Participants with TB presumptive signs were asked to submit sputum specimen(s). Sputum smear, culture, and polymerase chain reaction analyses were performed. Cascade analysis, chi-squared tests, and Fisher exact tests were used to evaluate screening performance. Results: In total, 12,402 participants were screened, and 211 (1.7%) were suspected to have active TB; 181 of the suspected patients (85.8%) underwent sputum smear test, and 16 (8.8%) patients were confirmed to have TB. The TB prevalence among the elderly was bacteriologically confirmed to be 129 per 100,000 individuals, which was similar to national TB notification data for the same age groups. The proportion of active TB cases increased with age, and differed based on sex and past TB history. However, TB-related symptoms, comorbidity status, and TB screening history within 12 months were not predictive of active TB. Conclusion: This study identified that the prevalence rate was similar to national TB notification data from the same age groups. Periodic, community-based, systematic TB screening among the elderly population is recommended.

• Tuberculosis and Respiratory Diseases
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• v.78 no.4
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• pp.349-355
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• 2015

Background: The tuberculin skin test (TST) is the standard tool to diagnose latent tuberculosis infection (LTBI) in mass screening. The aim of this study is to find an optimal cut-off point of the TST+ rate within tuberculosis (TB) contacts to predict the active TB development among adolescents in school TB outbreaks. Methods: The Korean National Health Insurance Review and Assessment database was used to identify active TB development in relation to the initial TST (cut-off, 10 mm). The 7,475 contacts in 89 schools were divided into two groups: Incident TB group (43 schools) and no incident TB group (46 schools). LTBI treatment was initiated in 607 of the 1,761 TST+ contacts. The association with active TB progression was examined at different cut-off points of the TST+ rate. Results: The mean duration of follow-up was $3.9{\pm}0.9years$. Thirty-three contacts developed active TB during the 4,504 person-years among the TST+ contacts without LTBI treatment (n=1,154). The average TST+ rate for the incident TB group (n=43) and no incident TB group (n=46) were 31.0% and 15.5%, respectively. The TST+ rate per group was related with TB progression (odds ratio [OR], 1.025; 95% confidence interval [CI], 1.001-1.050; p=0.037). Based on the TST+ rate per group, active TB was best predicted at TST+ ${\geq}$ 16% (OR, 3.11; 95% CI, 1.29-7.51; area under curve, 0.64). Conclusion: Sixteen percent of the TST+ rate per group within the same grade students can be suggested as an optimal cut-off to predict active TB development in middle and high schools TB outbreaks.

• Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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• v.19 no.1
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• pp.43-46
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• 2008

Background and Objectives : Clinical suspicion and appropriate diagnostic procedures are essential for the timely management of extrapulmonary type of mycobacterial disease. In the hope of suggesting a suitable guideline for the early diagnosis of laryngeal tuberculosis, the authors reviewed their clinical pathways and the characteristics of patients with laryngeal tuberculosis who were managed in the recent 10 years at a single tertiary referral hospital, Samsung Medical Center. Subjects and Method : Retrospective chart review was performed for the 25 adult patients with laryngeal tuberculosis. Among 25 cases, 12 were pathologically confirmed by laryngeal biopsy and the other 13 were clinically diagnosed by cumulative clinical information; definite laryngitis on laryngoscopy, positive AFB (acid fast bacillus) smear/culture or active pulmonary tuberculosis on chest X-ray, and substantial response to anti-tuberculosis medication. Results : Chest X-ray revealed active pulmonary tuberculosis in 72% of patients (N=18/25). Sputum AFB smear/culture was positive in 95% of all tested patients (N=21/22) and in 100% of the tested patients who have stable or no evidence of pulmonary tuberculosis (N=5/5). All patients except one who had coexisting laryngeal malignancy showed considerable improvement in their subjective symptoms and laryngeal findings within the first 2 months of anti-tuberculosis medications and they achieved complete response on subsequent sputum studies, chest X-ray and laryngeal findings after $7.0{\pm}2.3$ months of the medications. Conclusion : We suggest that chest X-ray and sputum AFB smear/culture to be the first step of work-up for the patients having laryngeal tuberculosis in suspicion since laryngeal tuberculosis is largely associated with active pulmonary tuberculosis and/or sputum AFB study offers high yield even in case of primary laryngeal tuberculosis. However laryngeal biopsy must be considered in case showing unsatisfactory response to the anti-tuberculosis medication for more than 2 months.

• Tuberculosis and Respiratory Diseases
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• v.79 no.4
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• pp.201-206
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• 2016

Active tuberculosis (TB) has a greater burden of TB bacilli than latent TB and acts as an infection source for contacts. Latent tuberculosis infection (LTBI) is the state in which humans are infected with Mycobacterium tuberculosis without any clinical symptoms, radiological abnormality, or microbiological evidence. TB is transmissible by respiratory droplet nucleus of $1-5{\mu}m$ in diameter, containing 1-10 TB bacilli. TB transmission is affected by the strength of the infectious source, infectiousness of TB bacilli, immunoresistance of the host, environmental stresses, and biosocial factors. Infection controls to reduce TB transmission consist of managerial activities, administrative control, engineering control, environmental control, and personal protective equipment provision. However, diagnosis and treatment for LTBI as a national TB control program is an important strategy on the precondition that active TB is not missed. Therefore, more concrete evidences for LTBI management based on clinical and public perspectives are needed.

• Tuberculosis and Respiratory Diseases
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• v.47 no.6
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• pp.757-767
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• 1999

Background: Diagnosis by smear and/or cultures of the Mycobacterium tuberculosis from body fluid or biopsy specimen is "Gold standard". However the sensitivity of the direct microscopy is relatively low and culture of mycobacteria is time consuming. Despite an explosion in the techniques of rapid identification of mycobacteria by molecular genetic means, it is laborious and expensive and then rapid, inexpensive serodiagnosis is interested in diagnosis of tuberculosis. But sensitivity and specificity of known serologic antigen is not full sufficient level and then new antigen develop and combination cocktails of new developed antigens by ELISA are needed. Method: To compare the efficacy of different mycobacterial specific antigen and to assess the applicability of the combination of several different antigens in the diagnosis of tuberculosis, five ELISA tests derived 14KDa, 16KDa, 19KDa, 23KDa, 38KDa were evaluated in 57 active pulmonary patient and 24 inactive post-therapy follow up patient and 48 normal control. Results: The optical densities of ELISA test with 14KDa, 16KDa, 19KDa, 23KDa, 38KDa were significantly higher in active tuberculosis cases than in normal control(P<0.001, P<0.001, P<0.027, P<0.001, P<0.001) and those with 16KDa, 38KDa were significant higher in active tuberculosis cases than in inactive post-therapy follow up cases(P<0.01. P<0.001) and those of 14KDa, 16KDa, 23KDa, 38KDa were significant higher in inactive post-therapy follow up cases than in normal control(P<0.008. P<0.01. P<0.006. P<0.001). The sensitivity of 14KDa, 16KDa, 19KDa, 23KDa, 38KDa in active pulmonary patient cases was 42.1%, 43.9%, 15.8%, 28.0%, 70.2%, respectively and the specificity of 14KDa, 16KDa, 19KDa, 23KDa, 38KDa in active pulmonary patient cases was 95.8%, 95.8%, 91.7%, 89.6%, 93.8%, respectively. The sensitivity and specificity of combination 38KDa with 16KDa was 87% and 93.7%. Conclusion: The sensitivity and specificity of new antigens for serodiagnosis of the tuberculosis still remains limited at around 70%, which makes its a poor diagnostic tool for disease confirmation. A combination of cocktail antigens provided by cut-off value adjustment for serodiagnosis of tuberculosis some improved diagnostic yield than single antigen serologic test.

• Biomedical Science Letters
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• v.20 no.3
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• pp.162-167
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• 2014

Tuberculosis (TB) is one of the major global health problems and it has been estimated that in 5~10% of Mycobacterium tuberculosis (MTB)-infected individuals, the infection progresses to an active disease. Numerous cytokines and chemokines regulate immunological responses at cellular level including stimulation and recruitment of wide range of cells in immunity and inflammation. In the present study, the mRNA expression levels of eight host immune markers containing of IFN-${\gamma}$, TNF-${\alpha}$, IL-2R, IL-4, IL-10, CXCL9, CXCL10, and CXCL11 in whole blood cells from active pulmonary TB patients were measured after T-cell mitogen (PHA) and MTB specific antigens (ESAT-6, CFP-10, and TB7.7). Among the TH1-type factors, IFN-${\gamma}$ mRNA expression was peaked at 4 h, TNF-${\alpha}$ and IL-2R mRNA expression was significantly high at the late time points (24 h) in active TB patients, TH2-type cytokine (IL4 and IL10) mRNA expression levels in both active TB and healthy controls samples did not changed significantly, and the mRNA expression of the three IFN-${\gamma}$-induced chemokines (CXCL9, CXCL10, and CXCL11) were peaked at the late time points (24 h) in active TB patients after MTB specific antigen stimulation. In conclusion, the mRNA expression patterns of the TB-related immune markers in response to the T-cell mitogen (PHA) differed from those in response to MTB specific antigens and these findings may helpful for understanding the relationship between MTB infection and host immune markers in a transcripts level.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.7 no.1
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• pp.102-107
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• 2004

About 20% of intestinal tuberculosis have active pulmonary tuberculosis. Intestinal tuberculosis can develop by swallowing sputum which have active pulmonary tuberculosis and by ingestion of contagious milk. We report a case of intestinal tuberculosis complicated with pulmonary tuberculosis in a 15-year old aldelescent who could not cough out sputum because of known cerebral palsy. He was admitted because of 3 day history of fever and bloody stool. Chest PA showed both upper lobe consolidation. AFB stain and AFB PCR was positive for tuberculosis. Colon study showed abscence of haustral marking and lead pipe appearance due to stenosis of ascending colon and mucosal edema. Abdominal CT scan showed mild wall thickening in ascending colon. Despite the anti-tuberculosis therapy with first line drugs, fever accompanying pleural effusion developed. Second line drug with Isoniazid and Rifampin improved clinical manifestation. After the report on sensitivity, we readjusted the regimen, and clinical manifestations improved gradually.