• Tuberculosis and Respiratory Diseases
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• 제81권1호
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• pp.59-72
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• 2018

Background: It remains uncertain if $interferon-{\gamma}$ release assays (IGRAs) are superior to the tuberculin skin test (TST) for the diagnosis of active tuberculosis (TB) or latent tuberculosis infection (LTBI) in immunosuppressed populations including people with human immunodeficiency virus (HIV) infection. The purpose of this study was to systematically review the performance of IGRAs and the TST in people with HIV with active TB or LTBI in low and high prevalence TB countries. Methods: We searched the MEDLINE database from 1966 through to January 2017 for studies that compared results of the TST with either the commercial QuantiFERON-TB Gold in Tube (QFTGT) assay or previous assay versions, the T-SPOT.TB assay or in-house IGRAs. Data were summarized by TB prevalence. Tests for concordance and differences in proportions were undertaken as appropriate. The variation in study methodology was appraised. Results: Thirty-two studies including 4,856 HIV subjects met the search criteria. Fourteen studies compared the tests in subjects with LTBI in low TB prevalence settings. The QFTGT had a similar rate of reactivity to the TST, although the first-generation version of that assay was reactive more commonly. IGRAs were more frequently positive than the TST in HIV infected subjects with active TB. There was considerable study methodology and population heterogeneity, and generally low concordance between tests. Both the TST and IGRAs were affected by CD4 T-cell immunodeficiency. Conclusion: Our review of comparative data does not provide robust evidence to support the assertion that the IGRAs are superior to the TST when used in HIV infected subjects to diagnose either active TB or LTBI.

• Tuberculosis and Respiratory Diseases
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• 제81권1호
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• pp.6-12
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• 2018

The role of the treatment for latent tuberculosis infection (LTBI) has been underscored in the intermediate tuberculosis (TB) burden countries like South Korea. LTBI treatment is recommended only for patients at risk for progression to active TB-those with frequent exposure to active TB cases, and those with clinical risk factors (e.g., immunocompromised patients). Recently revised National Institute for Health and Care Excellence (NICE) guideline recommended that close contacts of individuals with active pulmonary or laryngeal TB, aged between 18 and 65 years, should undergo LTBI treatment. Various regimens for LTBI treatment were recommended in NICE, World Health Organization (WHO), and Centers for Disease Control and Prevention guidelines, and superiority of one recommended regimen over another was not yet established. Traditional 6 to 9 months of isoniazid (6H or 9H) regimen has an advantage of the most abundant evidence for clinical efficacy-60%-90% of estimated protective effect. However, 6H or 9H regimen is related with hepatotoxicity and low compliance. Four months of rifampin regimen is characterized by less hepatotoxicity and better compliance than 9H, but has few evidence of clinical efficacy. Three months of isoniazid plus rifampin was proved equivalence with 6H or 9H regimen in terms of efficacy and safety, which was recommended in NICE and WHO guidelines. The clinical efficacy of isoniazid plus rifapentine once-weekly regimen for 3 months was demonstrated recently, which is not yet introduced into South Korea.

• Pediatric Infection and Vaccine
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• 제15권1호
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• pp.52-58
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• 2008

목 적 : 잠복 결핵 감염 진단 시 사용되는 고전적인 방법인 투베르쿨린 피부 반응 검사(TST) 외 전혈에서 인터페론 감마의 분비능을 측정하는 검사가 개발된 이후 많은 연구들이 그 유용성을 입증하였으나, 소아에서는 그러한 평가가 제한되어 있다. 본 연구는 결핵에 노출된 소아의 잠복 결핵 감염 진단에 있어 QuantiFERON-TB Gold 검사의 유용성을 알아보고자 하였다. 방 법 : 2006년 1월부터 2007년 12월까지 분당 서울 대학교 병원에 결핵 환자와 접촉하여 내원한 소아를 대상으로 흉부 방사선 사진, TST 및 QuantiFERON-TB Gold 검사를 시행하였다. 초기 TST가 음성인 경우, 3개월 뒤 추적 검사를 시행하였다. TST 결과에 따라 초기 TST가 양성인 경우 감염 여부는 확실치 않으나 잠복 감염의 가능성이 있는 군, 초기 TST는 음성이었으나 3개월 뒤 검사에서 양성 전환된 경우는 잠복 결핵 감염군, 처음과 3개월 뒤 TST가 모두 음성인 경우는 감염되지 않은 군으로 정의하였다. 초기 TST가 음성이었으나 추적검사를 하지 않은 경우는 분석에서 제외시켰다. 결 과 : 대상군은 총 49명(남자 22명, 여자 27명) 이었으며, 중앙 연령은 75세(범위; 3개월-14.7세)이었다. QuantiFERON-TB Gold 검사 양성을 보인 소아는 총 5명으로, 감염 여부는 확실치 않으나 잠복 감염의 가능성이 있는 13명 중 3례(23.1%), 잠복 결핵 감염으로 진단된 8명 중 1례(13%), 그리고 감염되지 않은 21명 중 1례(5%)가 포함되었다. QuantiFERON-TB Gold와 TST의 일치도는 0.72이었다(${\kappa}=0.101$). TST와 비교하였을 때 QuantiFERON-TB Gold의 민감도는 12.5%(1/8), 특이도는 95.2%(20/ 21)으로 나타났다. 결 론 : 결핵에 노출된 소아의 잠복결핵감염의 진단에 있어서 QuantiFERON-TB Gold 검사는 TST에 비하여 민감도가 매우 낮아서 임상적 유용성이 불확실하며 더 많은 연구가 필요하다.

• 근관절건강학회지
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• 제26권2호
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• pp.120-130
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• 2019

Purpose: The purpose of this study was to investigate the predictors of tuberculosis (TB) drugs in health care workers diagnosed with latent tuberculosis Infection (LTBI). Methods: This study was a descriptive correlation study. Data were collected by using a self-report questionnaire. The collected data were analyzed by -test, t-test, and logistic regression analysis. Results: There were involved 160 participants, 35 (21.9%) who took the TB drugs, and 125 (73.8%) who did not take the TB drugs. The predictors on taking TB drugs in health care workers with LTBI were subjective norms (OR=3.33, p<.001), perceived sensitivity (OR=2.67, p=.026), perceived barrier (OR=0.14, p=.014), and unmarried (OR=4.69, p=.006) than married, health care worker category 2 group (OR=5.84, p=.015) and 1 group (OR=4.25, p=.022) than 3, 4 group, sleep over 7 hours (OR=4.11, p=.022) than less 7 hours sleep. Conclusion: In order to promote the use of TB drugs in health care workers with LTBI, it is necessary that take intervention strategies to increase the subjective norms and perceived sensitivity and to decrease the perceived barriers.

• 한국산업보건학회지
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• 제29권3호
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• pp.289-297
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• 2019

Objectives: To identify the positive rate of and the risk factors associated with latent tuberculosis infection(LTBI) in mine workers, the objectives of the present study evaluated those among former mine workers. Methods: Between January 2015 and May 2017, former male mine workers who had been subjects for epidemiology research for work-related chronic obstructive pulmonary disease(COPD) and had received QuantiFERON-$TB^{(R)}$ Gold In-Tube(QFT-GIT) from the Institute of Occupation and Environment(IOE) under Korea Workers' Compensation and Welfare Service(KCOMWEL) were selected as the study subjects. To identify significant variables for increased risk of LTBI, logistic regression analysis was performed. Results: A total of 736 male former mine workers were selected as study subjects. The positive rate of LTBI among subjects was 69.2%(509/736). The current smoking[odds ratio(OR), 2.3; 95% confidence interval(CI), 1.1-4.9], COPD(OR, 1.4; 95% CI, 0.9-2.3), department loading(OR, 1.8; 95% CI, 0.9-3.4) and mining(OR, 1.5; 95% CI, 0.9-2.5), and working duration of over 20(OR, 1.6; 95% CI, 0.9-3.1) and over 30 years(OR, 2.2; 95% CI, 0.9-4.9) were associated with increased risk of LTBI. The interferon-gamma(IFN-${\gamma}$) level after stimulation with Mycobacterium tuberculosis(MTB)-specific antigens showed a significantly negative correlation with age(r=-0.126). Conclusions: The present study determined that the high positive rate of LTBI among mine workers was associated with not only the host factors but also the occupational exposure to mine dust.

• The Korean journal of internal medicine
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• 제33권6호
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• pp.1241-1251
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• 2018

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.

• Pediatric Infection and Vaccine
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• 제20권1호
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• pp.17-27
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• 2013

목 적 : 잠복결핵감염(LTBI)을 진단하는 방법은 결핵 피부반응검사(TST)와 interferon-${\gamma}$ releasing assay(IGRA)이다. 그런데 TST의 위양성 문제 때문에 TST 대신 IGRA로 대치하려는 경향이 있다. 이에 결핵 접촉자 조사를 시행함에 있어 TST와 QuantiFERON$^{(R)}$-TB Gold In-Tube (QFT-GIT) 검사를 동시에 시행하여 결과를 비교하였다. 방 법 : 2007년 2월부터 2008년 5월까지 가톨릭대학교 성빈센트병원 소아청소년과 외래에 LTBI 여부의 확인을 위해 방문한 소아를 대상으로 TST와 QFT-GIT 검사를 동시에 시행하였다. 연구대상은 감염원이 같은 집에 거주하는 경우를 동거 접촉, 아닌 경우를 비동거 접촉으로 구분하였다. 결 과 : 연구대상은 총 35명으로 폐결핵 노출 후 접촉자 조사 대상이 29명, 폐결핵으로 진단된 경우가 6명이었다. 접촉자 조사 대상에서 동거 접촉군은 18명(62.1%), 비동거 접촉군이 11명(37.9%)이었다. 최종 접촉자 조사 결과로 TST 양성은 동거 접촉군 38.9% (7/18), 비동거 접촉군 45.5% (5/11)이었고, QFT-GIT 검사 양성은 각각 5.6% (1/18), 9.1%(1/11)로 TST의 양성률이 더 높았다. 접촉자 조사에서 두 검사를 모두 시행한 경우는 1차 검사의 26건과 2차 추적검사의 15건을 합하여 총 41건으로 두 검사의 일치율(kappa값)은 0.063으로 매우 낮았다. 6명의 폐결핵 환자에서 TST는 모두 양성, QFT-GIT 검사는 5명이 양성으로, 이들까지를 포함했을 때의 일치율은 0.334이었다. 결 론 : 본 연구에서 TST와 QFT-GIT 검사 결과의 일치율은 낮았는데, 대부분이 TST 양성인 경우이었다. 두 검사 결과 중 어떤 것이 정확한 것인지 판단할 수 있는 표준 검사법이 없고, 소아청소년에 대한 자료가 충분치 않은 상황에서 민감도가 낮은 IGRA에 의한 결과만을 신뢰하여 LTBI 진단에 IGRA만 사용하는 것은 적절치 않다고 사료된다.

• Pediatric Infection and Vaccine
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• 제26권1호
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• pp.32-41
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• 2019

목적: 결핵 전파를 조기에 차단하기 위해서는, 활동성 결핵 환자와 접촉한 사람들을 조사하여 결핵 질환 및 잠복결핵감염을 진단하고 치료하는 것이 매우 중요하며, 국내에서는 민간-공공협력 결핵관리사업을 통해 적극적인 접촉자 조사 활동을 지원하고있다. 본연구에서는최근 3년간단일기관에서이루어진소아청소년연령에서의접촉자검진과소아잠복결핵감염치료 현황에 대해 조사하였다. 방법: 2014년 7월 1일부터 2017년 6월 30일까지 충남대학교병원에서 활동성 결핵 환자로 진단받은 환자들을 대상으로 가족 내 소아청소년 접촉자에 대한 검진을 시행하여 접촉자 검진 완료율 및 결과를 분석하였고, 이와 함께 동일 기간 동안 잠복결핵감염으로 치료 받은 소아청소년 환자들의 치료 현황을 후향적으로 검토하였다. 결과: 연구 기간 동안 본 기관에서 활동성 결핵 환자는 총 1,002명 진단되었고, 그 중 소아청소년 가족접촉자가 있는 환자는 171명이었다. 소아청소년 접촉자 269명 중 20명(7.4%)은 검진을 전혀 받지 않았다. 1차 검진을 받은 249명 중 폐결핵이 1명(0.4%) 진단되었고, 7명(2.8%)은 과거의 결핵 감염 병력이 있었으며, 42명(16.9%)이 잠복결핵감염으로 진단되었다. 2차 검진 시 29명(11.6%)이 추가로 잠복결핵감염으로 진단되었으며, 2차 검진까지 필요하였으나 검진을 완료하지 않은 사람이 61명으로 총 접촉자 269명 중 188명(69.9%)만이 필요한 검진을 완료하였다. 잠복결핵감염으로 치료받은 소아청소년 환자는 90명이었으며 83명(92.2%)이 치료를 완료하였고, 이 중 18명이 발진(8명), 피로(5명), 위장장애(5명) 등의 부작용을 호소하였으나 치료 중단이 필요한 심각한 부작용은 없었다. 결론: 민간-공공협력 결핵관리사업 도입 및 보편화 후에도 소아청소년 연령에서의 결핵 접촉자 검진 완료율은 낮았으며, 잠복결핵감염으로 진단받은 소아의 항결핵제 치료 시 심각한 부작용의 발생 없이 투약 완료율이 높게 나타났다. 향후 결핵 전파의 예방 및 관리를 위해 더욱 적극적인 민관 협동 노력 및 환자, 보호자 교육이 필요하겠다.

• 대한의생명과학회지
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• 제19권2호
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• pp.90-97
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• 2013

The tuberculin skin test (TST) and interferon gamma (IFN-${\gamma}$) release assay (IGRA) have been widely used for diagnosis of latent tuberculosis infection (LTBI). In order to overcome limitations of current LTBI diagnostic methods, the development of a novel molecular assay which is able to measure the IFN-${\gamma}$ messenger RNA (mRNA) expression level after stimulation with Mycobacterium tuberculosis (MTB) specific antigen was recently developed. The ability of a molecular assay to detect MTB infection was similar to commercial IGRA however, the optimal incubation time for stimulating IFN-${\gamma}$ was not yet established. Therefore, in this study the direct comparisons of MTB Ag stimulation times (4 and 24 hrs) were performed for diagnosis of MTB infection. Data showed that the coincident rate between QFT-GIT IFN-${\gamma}$ ELISA and IFN-${\gamma}$ RT-PCR (4 hrs) was 88.35% and that of QFT-GIT and IFN-${\gamma}$ RT-PCR (24 hrs) was 70.85%. Based on a receiver operating characteristic (ROC) curve, the 4 hrs-MTB specific Ag stimulation time for IFN-${\gamma}$ RT-PCR had the significant P value, 95% CI value, and AUC (P < 0.0001, 95% CI=0.82 to 1.02, and AUC=0.9214) in comparison with 24 hrs-MTB specific Ag stimulation time (P = 0.009, 95% CI=0.06 to 0.94, and AUC=0.7711). These results show that 4-hr was the most optimal MTB Ag stimulation time for performing IFN-${\gamma}$ RT-PCR. Although semi-quantitative RT-PCR had a few analytical limitations, it might be useful as an alternative molecular diagnostic method for detecting MTB infection.

• Clinical and Experimental Pediatrics
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• 제61권11호
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• pp.366-370
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• 2018

Purpose: Tuberculosis (TB) is one of the most important diseases that cause significant mortality and morbidity in young children. Data on TB transmission from an infected child are limited. Herein, we report a case of disseminated TB in a child and conducted a contact investigation among exposed individuals. Methods: A 4-year-old child without Bacille Calmette-$Gu{\acute{e}}rin$ vaccination was diagnosed as having culture-proven disseminated TB. The child initially presented with symptoms of inflammatory bowel disease, and nosocomial and kindergarten exposures were reported. The exposed individuals to the index case were divided into 3 groups, namely household, nosocomial, or kindergarten contacts. Evaluation was performed following the Korean guidelines for TB. Kindergarten contacts were further divided into close or casual contacts. Chest radiography and tuberculin skin test or interferon-gamma-releasing assay were performed for the contacts. Results: We examined 327 individuals (3 household, 10 nosocomial, and 314 kindergarten contacts), of whom 18 (5.5%), the brother of the index patient, and 17 kindergarten children were diagnosed as having latent TB infection (LTBI). LTBI diagnosis was more frequent in the children who had close kindergarten contact with the index case (17.1% vs. 4.4%, P=0.007). None of the cases had active TB. Conclusion: This is the first reported case of TB transmission among young children from a pediatric patient with disseminated TB in Korea. TB should be emphasized as a possible cause of chronic diarrhea and failure to thrive in children. A national TB control policy has been actively applied to identify Korean children with LTBI.