• Tuberculosis and Respiratory Diseases
• /
• v.82 no.4
• /
• pp.306-310
• /
• 2019

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) ${\geq}10mm$ (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 ($42.8{\pm}9.9years$ vs. $35.4{\pm}10.0years$, p<0.01). Additionally, the mean TST size was significantly bigger in NKR ($17.39{\pm}3.9mm$ vs. $16.57{\pm}4.2mm$, 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.

• Tuberculosis and Respiratory Diseases
• /
• v.68 no.6
• /
• pp.328-333
• /
• 2010

Background: There are several active tuberculosis (TB) cases in Korean high schools each school year. The risk of transmission in schools is extremely high due to the considerable time spent in closed classrooms. We evaluated the control of latent tuberculosis infection in Korean high schools. Methods: When a student was identified with active TB, tuberculin skin testing was performed on their classmates and on students in their same school grade. When a student had a positive tuberculin skin tests (TST), they underwent follow-up testing with QuantiFERON-TB Gold In-Tube (QFT). The manufacturer recommended a cut-off of 0.35 IU/mL to determine QFT positivity was applied. Results: A total of 131 pulmonary tuberculosis (TB) patients were included based on the criteria for screening TB contacts in the National Tuberculosis Control Program. Seventy-five (57.2%) students tested smear positive. TST were performed on 7,109 students who were classmates of, or in the same grade as, a TB patient. Of the contacts, 1,231 students (17.3%) were TST positive and they were screened with QFT. Six hundred-sixty-six (55.0%) of the tested students returned a positive QFT result and the rate of positivity was significantly associated with the increasing size of TST indurations (p<0.0001). Conclusion: The use of QFT resulted in approximately 45% of TST positive students not being given chemoprophylaxis.

• Tuberculosis and Respiratory Diseases
• /
• v.81 no.1
• /
• pp.59-72
• /
• 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.

• Annals of dermatology
• /
• v.30 no.6
• /
• pp.716-720
• /
• 2018

Perforating granuloma annulare (PGA), a rare variant of granuloma annulare, is characterized by transepidermal elimination of altered collagen that clinically manifests an umbilicated papule with a central crust. It can be confused with papulonecrotic tuberculid (PNT) because of their similar appearance. Unlike PGA, PNT is usually related to tuberculosis infection with a typical histologic finding of wedgeshaped dermal necrosis. Here, we report the first Korean case of PGA mimicking PNT both clinically and histologically. A 43-year-old Korean woman presented with erythematous papules localized on the extensor surface of her limbs for one year. Some of these papules had a central umbilication or a crust. Regarding comorbidity, she had latent tuberculosis diagnosed with $QuantiFERON^{(R)}-TB$ Gold test about five months ago. She was on antituberculous medication. Initially, a diagnosis of papulonecrotic tuberculid accompanied by latent tuberculosis was considered. However, despite taking the antituberculous medication for five months, her skin lesions were not improved. Biopsy specimen from her arm lesion showed wedge-shaped area of necrosis in the dermis. Additionally, there were multiple focal mucin depositions and palisading granulomatous inflammation throughout the dermis. A diagnosis of PGA was made and she was treated with topical corticosteroid. After two weeks of applying topical corticosteroid, most of her skin lesions disappeared, leaving some hyperpigmented scars.

• Journal of Microbiology and Biotechnology
• /
• v.25 no.8
• /
• pp.1181-1194
• /
• 2015

Tuberculosis (TB) is an infectious disease transmitted by aerosol droplets and characterized by forming granulomatous lesions. Although the number of people infected in the population is high, the vast majority does not exhibit symptoms of active disease and only 5-10% develop the disease after a latent period that can vary from weeks to years. The bases of the immune response for this resistance are unknown, but it depends on a complex interaction between the environment, the agent, and the host. The analysis of cellular components of M. tuberculosis shows important host-pathogen interactions, metabolic pathways, virulence mechanisms, and mechanisms of adaptation to the environment. However, the M. tuberculosis proteome still remains largely uncharacterized in terms of virulence and pathogenesis. Here, we summarize some of the major proteomic studies performed to scrutinize all the mycobacterial components.

• Tuberculosis and Respiratory Diseases
• /
• v.78 no.4
• /
• pp.349-355
• /
• 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 Microbiology and Biotechnology
• /
• v.26 no.3
• /
• pp.588-595
• /
• 2016

IFN-γ release assays (IGRAs) have been developed as viable alternative diagnostic tools for detecting latent tuberculosis infection (LTBI). A customized homogeneous sandwich luminescent oxygen channeling immunoassay (LOCI) was used to quantify IFN-γ levels in IGRAs. Samples were collected from healthy volunteers (n = 40) who were T-Spot-negative and T-Spot-positive patients (n = 32) at rest. Then the amount of IFN-γ in the supernatant of IGRAs was measured by LOCI. The results demonstrated a low background, and high sensitivity, specificity, accuracy, and reproducibility, and a short assay time (only 30 min) with LOCI for IFN-γ. The recovery range was 81.63-102.06%, the coefficients of variation were below 5%, and the limit of detection was 19.0 mIU/ml. Excellent agreement between LOCI IFN-γ and the T-SPOT.TB test was obtained (97.2% agreement, κ = 0.94). The LOCI IFN-γ concentrations were significantly higher in T-Spot-positive patients than in the healthy group (p < 0.001). Moreover, as observed for the comparative LOCI IFN-γ assay, IFN-γ concentrations were related to the numbers of T-SPOT.TB spots. We have established an in vitro blood test for LTBI diagnosis, defined as LOCI IFN-γ. A high level of agreement between the LOCI IFN-γ method and T-SPOT.TB assay was observed in clinical studies that showed the LOCI IFN-γ method could determine LTBI. This study shows acceptable performance characteristics of the LOCI IFN-γ assay to diagnose LTBI.

• Biomedical Science Letters
• /
• v.19 no.2
• /
• pp.90-97
• /
• 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.

• Tuberculosis and Respiratory Diseases
• /
• v.75 no.1
• /
• pp.18-24
• /
• 2013

Background: We investigated the prevalence of latent tuberculosis infection (LTBI) among the health care workers (HCWs) and analyzed its risk factors in South Korea. Methods: A standard questionnaire regarding the baseline demographics and risk factors for LTBI was given to each participant and tuberculin skin test (TST), QuantiFERON-TB GOLD In-Tube (QFT-GIT) assay, and chest radiography were performed. Results: A total of 493 participants, 152 (30.8%) doctors and 341 (69.2%) nurses were enrolled in eight tertiary referral hospitals. The mean age of the subjects was 30.6 years old, and 383 (77.7%) were female. Of the 152 doctors, 63 (41.4%) and 36 (23.7%) were positive by TST and by QTF-GIT, respectively, and among the 341 nurses, 119 (34.9%) and 49 (14.4%) had positive TST and QFT-GIT results, respectively. Overall, the agreement between the two tests was 0.22 by the chance corrected proportional agreement rate (kappa coefficient) in 493 subjects. Experience of working in tuberculosis (TB)-related departments was significantly associated with positive LTBI test results by QFT-GIT assay, not by TST. In multivariate analysis, only age was independently associated with increased risk of a positive TST result, while age and experience of working in TB-related departments (odds ratio, 2.29; 95% confidence interval, 1.01-5.12) were independently associated with increased risk of a positive QFT-GIT result. Conclusion: A high prevalence of LTBI was found among South Korean HCWs. Considering the association between the experience of working in TB-related departments and high risk of LTBI, QFT-GIT may be a better diagnostic test for LTBI than TST in HCWs.

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