• Tuberculosis and Respiratory Diseases
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• v.73 no.3
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• pp.143-150
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• 2012

Background: The release of interferon-gamma (IFN-${\gamma}$) by T lymphocytes increases after rechallenge with Mycobacterium tuberculosis antigen, especially, at a localized site of tuberculosis (TB) infection. We aimed to compare the clincial efficacy of two commercial IFN-${\gamma}$ release assays from pleural fluid for the diagnosis in tuberculous pleurisy. Methods: We performed T-SPOT.TB and QuantiFERON-TB Gold tests simultaneously on pleural fluid and peripheral blood samples from patients with pleural effusion, in South Korea, an area with intermediate TB burden. Results: Thirty-six patients were enrolled prospectively, and tuberculous pleurisy was found in 21 patients. Both the numbers of IFN-${\gamma}$ secreting T cells and the concentration of IFN-${\gamma}$ were greater in the pleural tuberculous group, comparing with the non-tuberculous group. Moreover, in the tuberculous group, there was a significant difference in IFN-${\gamma}$ producing spot-forming cells using the T-SPOT.TB method between pleural fluid and peripheral blood. The receiver operating characteristic (ROC) curve, was the greatest for pleural fluid T-SPOT.TB test, followed by peripheral blood T-SPOT.TB test, peripheral blood QuantiFERON-TB Gold test, and pleural fluid QuantiFERON-TB Gold test (area under the ROC curve of 0.956, 0.890, 0.743, and 0.721, respectively). The T-SPOT.TB assay produced less indeterminate results than did QuantiFERON-TB Gold assay in both pleural fluid and peripheral blood. Conclusion: These findings suggest that the pleural fluid T-SPOT.TB test could be the most useful test among the IFN-${\gamma}$ release assays for diagnosing tuberculous pleurisy in an area with an intermediate prevalence of TB infection.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.78 no.2
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• pp.56-63
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• 2015

A small number of viable tuberculosis bacilli can reside in an individual with latent tuberculosis infection (LTBI) without obvious clinical symptoms or abnormal chest radiographs. Diagnosis and treatment for LTBI are important for tuberculosis (TB) control in public and private health, especially in high-risk populations. The updated 2014 Korean guidelines for TB recommend that tuberculin skin tests, interferon-gamma release assays, or a combination of the two can be used for LTBI diagnosis according to age and immune status of the host as well as TB contact history. The regimens for LTBI treatment include isoniazid, rifampicin, or isoniazid/rifampicin. However, results of drug susceptibility test from the index case must be considered in selecting the appropriate drug for recent contacts. Standardized LTBI diagnosis and treatment based on the new 2014 guidelines will contribute to the effective TB control in Korea as well as to the establishment of updated guidelines.

• Tuberculosis and Respiratory Diseases
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• v.81 no.1
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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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• 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.

• 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.80 no.1
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• pp.21-26
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• 2017

It is well established that health care workers (HCWs) have a considerably higher risk of occupationally acquired tuberculosis (TB). To reduce the transmission of TB to HCWs and patients, TB infection control programs should be implemented in health care settings. The first and most important level of all protection and control programs is administrative control. Its goals are to prevent HCWs, other staff, and patients from being exposed to TB, and to reduce the transmission of infection by ensuring rapid diagnosis and treatment of affected individuals. Administrative control measures recommended by the United States Centers for Disease Control and Prevention and the World Health Organization include prompt identification of people with TB symptoms, isolation of infectious patients, control of the spread of the pathogen, and minimization of time spent in health care facilities. Another key component of measures undertaken is the baseline and serial screening for latent TB infection in HCWs who are at risk of exposure to TB. Although the interferon-gamma release assay has some advantages over the tuberculin skin test, the former has serious limitations, mostly due to its high conversion rate.

• The Korean journal of internal medicine
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• v.33 no.6
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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.

• Tuberculosis and Respiratory Diseases
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• v.76 no.6
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• pp.261-268
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• 2014

Patients with immune-mediated inflammatory diseases (IMIDs) are increasingly being treated with anti-tumor necrosis factor (TNF) agents and are at increased risk of developing tuberculosis (TB). Therefore, diagnosis and treatment of latent TB infection (LTBI) is recommended in these patients due to the initiation of anti-TNF therapy. Traditionally, LTBI has been diagnosed on the basis of clinical factors and a tuberculin skin test. Recently, interferon-gamma releasing assays (IGRAs) that can detect TB infection have become available. Considering the high-risk of developing TB in patients on anti-TNF therapy, the use of both a tuberculin skin test and an IGRA should be considered to detect and treat LTBI in patients with IMIDs. The traditional LTBI treatment regimen consisted of isoniazid monotherapy for 9 months. However, shorter regimens such as 4 months of rifampicin or 3 months of isoniazid/rifampicin are increasingly being used to improve treatment completion rates. In this review, the screening methods for diagnosing latent and active TB before anti-TNF therapy in patients with IMIDs will be briefly described, as well as the current LTBI treatment regimens, the recommendations for managing TB that develops during anti-TNF therapy, the necessity of regular monitoring to detect new TB infection, and the re-initiation of anti-TNF therapy in patients who develop TB.

• Tuberculosis and Respiratory Diseases
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• v.72 no.5
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• pp.416-425
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• 2012

Background: The sensitivities and specificities of interferon-gamma release assays (IGRAs) vary among different population studies, and the data on the routine use of IGRAs are limited. The aim of this study was to evaluate the role of QuantiFERON-TB Gold In-Tube (QFT-GIT) test in the diagnosis of active tuberculosis. Methods: We conducted a prospective study, enrolling 77 patients with suspected pulmonary tuberculosis (TB), at a secondary care teaching hospital in Seoul. Results: In total, 12 (15.6%) patients showed indeterminate results due to positive control failure on the QFT-GIT test. Indeterminate results were significantly associated with the elderly, history of the intensive care unit stay, lymphocytopenia, especially low CD4 count, increased C-reactive protein and decreased protein levels. Of the 77 patients, 44 (57.1%) were diagnosed with active pulmonary tuberculosis, and the percentage of false negative results of the QFT-GIT was 36.4% (vs. 31.8% with TST). In the TB group with >65 years old (n=12), the proportions of the indeterminate (33.3% vs. 3.1%) and the false negative results (58.3% vs. 25.0%) of the QFT-GIT were significantly higher than in the younger TB group (n=32). Conclusion: Indeterminate and false negative results of QFT-GIT test were not infrequent in tuberculosis, especially in the elderly. Care should be considered for the interpretation with the elderly, immunocompromised, chronic and severely diseased patients.