No abstract available.
Diagnosis* ; Korea* ; Latent Tuberculosis*

Tuberculosis (TB) is an infectious disease that poses a serious threat to human health. About a quarter of the world's population were infected with Mycobacterium tuberculosis in 2020, and the majority of them were latently infected. Approximately 5%-10% of the population with latent tuberculosis infection may progress to active TB disease. Identifying latent TB infection from active TB by biomarkers and screening people with latent TB infection at high risk of progression for preventive treatment by biomarkers that can reliably predict the progression is one of the most effective strategies to control TB. This article reviews the progress of research on transcriptional and immunological biomarkers for identifying TB infection and predicting the progression from latent infection to active TB, with the aim of providing new ideas for tuberculosis control.
Humans ; Latent Tuberculosis/diagnosis* ; Tuberculosis/diagnosis* ; Mycobacterium tuberculosis/genetics* ; Biomarkers

BACKGROUND: Differential diagnosis of active tuberculosis (ATB) and latent tuberculosis infection (LTBI) has been a challenge for clinicians in high TB burden countries. The purpose of this study was to improve the accuracy of differential diagnosis of ATB and LTBI by using fluorescent immunospot (FluoroSpot) assay to detect specific Th1 cell immune responses. The novel mycobacterium tuberculosis (MTB) latency-associated antigens Rv1733c and synthetic long peptides derived from Rv1733c (Rv1733c SLP) were used based on virulence factors early secreting antigen target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10). METHODS: Fifty-seven ATB cases, including 20 pathogen-confirmed ATB and 37 clinically diagnosed ATB, and 36 LTBI cases, were enrolled between January and December 2017. FluoroSpot assay was used to detect the interferon γ (IFN-γ) and interleukin 2 (IL-2) secreted by the specific T cells after being stimulated with MTB virulence factors ESAT-6 and CFP-10, MTB latency-associated antigens Rv1733c and Rv1733c SLP. The receiver operating characteristic (ROC) curve was used to define the best cutoff value of latency-associated antigens in the use of differentiating ATB and LTBI. The sensitivity, specificity, predictive value, and likelihood ratio of ESAT-6 and CFP-10-FluoroSpot combined with latency-associated antigen in the differential diagnosis of ATB and LTBI were also calculated. RESULTS: Following the stimulation with Rv1733c and Rv1733c SLP, the frequency of single IL-2-secreting T cells stimulated by Rv1733c SLP had the largest area under the ROC curve, which was 0.766. With a cutoff value of 1 (spot-forming cells [SFCs]/2.5 × 105 peripheral blood mononuclear cells) for frequency, the sensitivity and specificity of distinguishing ATB from LTBI were 72.2% and 73.7%, respectively. ESAT-6 and CFP-10-FluoroSpot detected the frequency and proportion of single IFN-γ-secreting T cells; the sensitivity and specificity of distinguishing ATB from LTBI were 82.5% and 66.7%, respectively. Combined with the frequency of single IL-2-secreting T cells stimulated by Rv1733c SLP on the basis of ESAT-6 and CFP-10-FluoroSpot, the sensitivity and specificity increased to 84.2% and 83.3%, respectively. CONCLUSION Rv1733c SLP, combined with ESAT-6 and CFP-10, might be used as a candidate antigen for T cell-based tuberculosis diagnostic tests to differentiate ATB from LTBI.
Antigens, Bacterial ; Diagnosis, Differential ; Humans ; Latent Tuberculosis/diagnosis* ; Leukocytes, Mononuclear ; Mycobacterium tuberculosis ; Tuberculosis/diagnosis*

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 µm 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.
Diagnosis ; Humans ; Infection Control ; Latent Tuberculosis* ; Mycobacterium tuberculosis ; Personal Protective Equipment ; Tuberculosis*

No abstract available.
Humans ; Interferon-gamma Release Tests ; Latent Tuberculosis/diagnosis ; Prospective Studies ; Reproducibility of Results ; Tuberculosis, Pulmonary/*diagnosis

BACKGROUND:The tuberculin skin test, which has been used for years for the diagnosis of latent tuberculosis, has many limitations, including false-positive results in individuals who were vaccinated with BCG. We evaluated the usefulness of a recently developed interferon-gamma assay (QuantiFERON-TB Gold) in the diagnosis of latent tuberculosis. METHODS:We performed the QuantiFERON-TB Gold assay in the following groups: 1) individuals with negative responses of tuberculin skin test in the regular health checkups for two consecutive years (n = 14), 2) individuals with no abnormal findings in low dose computed tomography in a health checkup (n = 22), 3) individuals with stable tuberculosis in low dose computed tomography in a health checkup (n = 10), 4) patients with M. tuberculosis in culture (n = 23), 5) patients with nontuberculous mycobacteria in culture (n = 6). RESULTS:In the QuantiFERON-TB Gold assay, all the group 1 showed negative results. 65.2% of the group 4 showed positive QuantiFERON-TB Gold results, while all the group 5 showed negative results. 22.7% of the group 2 and 60.0% of the group 3 showed positive QuantiFERON-TB Gold results. In addition, it was revealed that the stimulation with CFP-10 played a major role in the induction of interferon-gamma secretion. CONCLUSION:The QuantiFERON-TB Gold assay shows promise for the immunodiagnosis of latent tuberculosis using a whole-blood.
Diagnosis ; Humans ; Immunologic Tests* ; Interferon-gamma* ; Latent Tuberculosis* ; Mycobacterium bovis ; Nontuberculous Mycobacteria ; Skin Tests ; Tuberculin ; Tuberculosis

Introduction of tumor necrosis factor (TNF) inhibitor for the treatment of rheumatoid arthritis (RA) induces not only significant improvement of symptoms and signs of RA but also substantial inhibition of progressive joint damage. Such therapeutic efficacies of TNF inhibitor have led to a paradigm shift in the treatment of RA. In spite of its dramatic effect against RA, it is now well established that the use of TNF inhibitor significantly increases the risk of tuberculosis in patients with RA. Therefore some countries have presented guidelines in the use of TNF inhibitors for rheumatoid arthritis to reduce the risk of tuberculosis. Korea Food and Drug Association (KFDA) have also provided guidelines for treating latent tuberculosis when using TNF inhibitors. In this article, we reviewed the general epidemiology of tuberculosis and incidence rates of tuberculosis in RA patients and those of RA patients treated with TNF inhibitors. We also introduced methods for the diagnosis of latent tuberculosis, and various guidelines published in different countries in managing tuberculosis in RA patients who were to be treated with TNF inhibitors. Finally, we suggest requirement of more appropriate guidelines for Korean RA patients who are candidates for treatment with TNF-inhibitors.
Arthritis, Rheumatoid* ; Diagnosis ; Epidemiology ; Humans ; Incidence ; Joints ; Korea ; Latent Tuberculosis ; Tuberculosis* ; Tumor Necrosis Factor-alpha*

BACKGROUND: Recently, two commercialized whole-blood assays, QuantiFERON(R)-TB Gold (QFT) and T SPOT-TB(R)(SPOT), which measure the IFN-gamma released in the whole blood after being incubation with mycobacterial antigens, were approved for the diagnosis of a latent tuberculosis infection (LTBI). However, there is data on whether or not the previously used PPD skin tests (TST) have any influence on the diagnostic ability of these ex-vivo IFN-gamma assays. METHOD: Forty-six 15 year-old students who did not appear to be infected with Mycobacterium tuberculosis were enrolled in this study. The peripheral blood was collected and used for two IFN-gamma assays. The IFN-gamma assays and TST were performed at the baseline (1st). The TST was repeated two months later (2nd), and the IFN-gamma assays were repeated two (2nd) and four months (3rd) later only in those subjects who had negative results at the baseline in both the IFN-gamma assays and TST. An induration size > 10 mm was considered to be positive in the TST. RESULTS: The mean TST value was 3.1 +/- 5.4 mm (range: 0-20). Of the 46 subjects examined, 13 subjects (28.3%) showed positive results in the two-step TST. Nine (19.6%) were SPOT-positive and only one (2.2%) was QFT-positive. The 2nd and 3rd QFT were carried out in 23 and 25 all-negative subjects, respectively, and all showed negative results. The 2nd SPOT was performed in 23 subjects and only one (4.3%) showed a weak-positive result. CONCLUSION: Even though there were some discrepancies in the results of the two ex-vivo IFN-gamma assays, it appears that their results were not influenced by a previous TST carried out in two or four months earlier.
Adolescent ; Diagnosis ; Humans ; Interferon-gamma* ; Latent Tuberculosis* ; Mycobacterium tuberculosis ; Skin Tests* ; Skin* ; Tuberculin*

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-γ 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-γ 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-γ 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-γ 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.
Child* ; Diagnosis* ; Humans ; Interferon-gamma Release Tests ; Latent Tuberculosis* ; Skin Tests ; Tuberculin ; Tuberculosis

In order to eliminate tuberculosis worldwide by 2050, effective management of latent tuberculosis infection is essential, and policy-makers have begun to recognize the importance of scaling up preventive therapy. The current guideline recommends targeted latent tuberculosis infection testing that identifies high-risk groups based on risk stratification for progression from latent infection to active disease. Both the tuberculin skin test and interferon-gamma releasing assay have a similar diagnostic efficacy for predicting progression to active tuberculosis. The Korean guideline recommends 9-month isoniazid monotherapy as the standard treatment; however, more evidence supports that short course rifampicin-based regimen is both more effective and tolerable than isoniazid monotherapy.
Diagnosis ; Interferon-gamma ; Interferon-gamma Release Tests ; Isoniazid ; Latent Tuberculosis ; Skin Tests ; Tuberculin ; Tuberculosis