• 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.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.

• Biomedical Science Letters
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• v.24 no.2
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• pp.138-142
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• 2018

The incidence of tuberculosis (TB) in the Republic of Korea remains high when compared to the incidence in other Organization for Economic Cooperation and Development (OECD) countries. The prompt diagnosis and effective treatment of latent TB infection (LTBI) are very important in terms of controlling the burden of TB. The tuberculin skin test (TST) has long been the "gold standard" assay for the diagnosis of LTBI. However, it can show false positive results due to Bacille Calmette-$Gu{\acute{e}}rin$ (BCG) vaccination and infection with many environmental nontuberculous mycobacteria (NTM). The interferon gamma release assay (IGRA) using Mycobacterium tuberculosis (MTB)-specific antigens, was developed for the detection of LTBI. The QuantiFERON-TB Gold In-Tube assay is one of the most commonly used forms of the IGRA. In order to compare the diagnostic efficacy of the TST and IGRA in relation to LTBI among BCG-vaccinated healthy donors, whole blood samples were collected from 51 participants, and the results of the TST and IGRA were compared. Of the 51 cases, 18 cases (35.3%) were positive and 33 cases (64.7%) were negative when using the TST, while four cases (7.8%) were positive and 47 cases (92.2%) negative when using the IGRA. There was no correlation between the size of the induration in the TST and the $IFN-{\gamma}$ protein level. In conclusion, the TST showed higher cross-reactivity among the BCG-vaccinated healthy participants, therefore, the IGRA might be the most suitable assay for the rapid screening of LTBI in BCG-vaccinated healthy population, or for TB contact investigation.

• Journal of Microbiology and Biotechnology
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• v.26 no.3
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• pp.588-595
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• 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.

• 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.

• 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.

• 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.

• 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.67 no.4
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• pp.331-337
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• 2009

Background: The whole-blood interferon-gamma release assay (QuantiFERON-TB Gold [QFT-G]: Cellestis, Carnegie, Victoria, Australia) has been studied primarily for the use of diagnosing active pulmonary tuberculosis (TB) or latent TB. In the present study, the usefulness of QFT-G was evaluated for the diagnosis of extra-pulmonary tuberculosis (EP-TB). Methods: From June 2006 to February 2009, we evaluated the usefulness of QFT-G in patients (n=65) suspected with EP-TB, retrospectively. The diagnostic sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the QFT-G assay were analyzed. Results: EP-TB was diagnosed in 33 (51%) participants. The overall sensitivity, specificity, PPV, and NPV of the QFT-G assay for EP-TB were 78%, 79%, 81%, and 77%, respectively. Of the 33 with EP-TB, 14 (42%) were diagnosed with TB pleurisy, 7 (21%) with TB lymphadenitis, 7 (21%) with intestinal TB, and 5 (15%) with EP-TB in other sites. In subgroup analyses according by site of infection, the QFT-G showed 86% sensitivity, 64% specificity, and 78% NPV in TB pleurisy. On the other hand, the sensitivity, specificity, and NPV of the assay were 71%, 83% and 71%, respectively in TB lymphadenitis, and 86%, 100% and 88%, respectively in intestinal TB. Among the patients with suspected alternative site EP-TB, the sensitivity, specificity, and NPV of the assay were 50%, 80% and 67%, respectively. Conclusion: The QFT-G assay showed moderate diagnostic accuracy in EP-TB. However, negative QFT-G assay does not exclude EP-TB because of the low NPV of this assay.