• Pediatric Infection and Vaccine
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• v.26 no.2
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• pp.89-98
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• 2019

Purpose: Despite the decline in tuberculosis (TB) incidence and mortality rates in the Republic of Korea through a national TB control program, TB remains one of the most critical infectious diseases in Korean children. We investigated the trends and research areas of published articles on TB in Korean children and adolescents. Methods: In 6 Korean and overseas databases, we searched titles and abstracts including "tuberculo*" or "TB," "child*" or "adolescen*" or "neonat*" or "infant*" or "pediatric*," and "korea*." The publication type, publication year, research areas, journal title, and research subjects were analyzed. Results: Out of the 257 searched documents, 120 papers were included in the analysis. Of these, 82 were original articles (68.3%), 33 case reports (27.5%), 4 review articles (3.3%), and 1 guideline (0.8%). In the original articles, the most common subject of studies was the clinical characteristics of patients with TB (36.6%), followed by diagnostics (29.3%), contact investigations (9.8%), epidemiology (6.1%), treatment (4.9%), vaccine (3.6%), latent TB infection (3.6%), complications (3.6%), and surveys on perception of TB (2.4%). From 1962, 4 articles were published in the 1960s, 10 articles in the 1970s, 11 articles in the 1980s, 22 articles in the 1990s, 26 articles in the 2000s, and 47 articles since 2010. Conclusions: The amount of research on TB in Korean children has increased over the past 5 decades; however, it has mainly focused on the clinical characteristics and diagnostics. Research in different areas, such as treatment and vaccine, is needed in the future.

• IMMUNE NETWORK
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• v.1 no.3
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• pp.250-259
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• 2001

To determine if initial infection with Mycobacterium tuberculosis changes the balance of cytokines between T cells and macrophages, we evaluated interferon (IFN)-${\gamma}$), interleukin-12 (IL)-12, and tumor necrosis factor (TNF)-${\alpha}$ productions by peripheral blood mononuclear cells (PBMC) from 15 untreated active pulmonary tuberculosis (TB) patients and 12 healthy tuberculin reactors (HTR). Freshly isolated PBMC were stimulated with Triton X-100 solubilized protein (TSP), 30-kDa or purified protein derivatives (PPD) antigen for 6, 18 and 96 hours. IL-12 p40 production by antigen-stimulated PBMC from TB patients was significantly decreased compared with that in HTR. In addition, IFN-${\gamma}$ production was significantly depressed in TB patients than that in HTR at a 96-hr stimulation. However, TNF-${\alpha}$ production was significantly higher in antigen-stimulated PBMC from TB than that of HTR. A pronounced increase in IFN-${\gamma}$ protein followed neutralization of IL-10 in early TB patients. However, neutralization of TNF-${\alpha}$ did not significantly alter IFN-${\gamma}$ induction in PBMC from TB patients. There were no significantly differences in the cytokine productions among three proteins, TSP, 30-kDa or PPD antigen. These results indicate that development of TB may be strongly associated with dysregulated productions of IL-12, IFN-${\gamma}$ and TNF-${\alpha}$, during the initial immune responses to M. tuberculosis. Further understanding of operative cytokine networks during human immune cell responses to protein antigens of M. tuberculosis may improve strategies for vaccine development.

• The Korean journal of internal medicine
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• v.39 no.1
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• pp.7-24
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• 2024

Post-tuberculosis lung disease (PTLD) is emerging as a significant area of global interest. As the number of patients surviving tuberculosis (TB) increases, the subsequent long-term repercussions have drawn increased attention due to their profound clinical and socioeconomic impacts. A primary obstacle to its comprehensive study has been its marked heterogeneity. The disease presents a spectrum of clinical manifestations which encompass tracheobronchial stenosis, bronchiectasis, granulomas with fibrosis, cavitation with associated aspergillosis, chronic pleural diseases, and small airway diseases-all persistent consequences of PTLD. The spectrum of symptoms a patient may experience varies based on the severity of the initial infection and the efficacy of the treatment received. As a result, the long-term management of PTLD necessitates a detailed and specific approach, addressing each manifestation individually-a tailored strategy. In the immediate aftermath (0-12 months after anti-TB chemotherapy), there should be an emphasis on monitoring for relapse, tracheobronchial stenosis, and smoking cessation. Subsequent management should focus on addressing hemoptysis, managing infection including aspergillosis, and TB-associated chronic obstructive pulmonary disease or restrictive lung function. There remains a vast expanse of knowledge to be discovered in PTLD. This review emphasizes the pressing need for comprehensive, consolidated guidelines for management of patients with PTLD.

• IMMUNE NETWORK
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• v.5 no.2
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• pp.117-123
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• 2005

The immune response to any stimulus is complex, requiring coordinated action by several types of cells in a tightly regulated sequence. Thus, a physical stress such as exercise may act at any number of points in the complex sequence of events collectively termed the immune response. Although exercise causes many propound changes in parameters of immune function, the nature and magnitude of such changes rely on several factors including the immune parameters of interest; type, intensity, and duration of exercise; fitness level or exercise history of the subject; environmental factors such as ambient temperature and humidity. Although regular moderate exercise appears to be important factor for increasing immunity, Athletes are susceptible to illness, in particular upper respiratory track infection, during periods of intense training and after competition. In addition, in elite athletes, frequent illness is associated with overtraining syndrome, a neuroendocrine disorder resulting from excessive training. Through this paper, we want to investigate the effects of exercise on the immunosuppression such as exercise induced lymphopenia, asthma, anaphylaxis, URT (upper respiratory track), and TB (tuberculosis) infection. and also, we want to suggest a direct mechanism, protection and therapy of exercise induced immunosuppression.

• IMMUNE NETWORK
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• v.23 no.2
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• pp.16.1-16.19
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• 2023

Bacillus Calmette-Guerin (BCG) vaccine is the only licensed vaccine for tuberculosis (TB) prevention. Previously, our group demonstrated the vaccine potential of Rv0351 and Rv3628 against Mycobacterium tuberculosis (Mtb) infection by directing Th1-biased CD4⁺ T cells co-expressing IFN-γ, TNF-α, and IL-2 in the lungs. Here, we assessed immunogenicity and vaccine potential of the combined Ags (Rv0351/Rv3628) formulated in different adjuvants as subunit booster in BCG-primed mice against hypervirulent clinical Mtb strain K (Mtb K). Compared to BCG-only or subunit-only vaccine, BCG prime and subunit boost regimen exhibited significantly enhanced Th1 response. Next, we evaluated the immunogenicity to the combined Ags when formulated with four different types of monophosphoryl lipid A (MPL)-based adjuvants: 1) dimethyldioctadecylammonium bromide (DDA), MPL, and trehalose dicorynomycolate (TDM) in liposome form (DMT), 2) MPL and Poly I:C in liposome form (MP), 3) MPL, Poly I:C, and QS21 in liposome form (MPQ), and 4) MPL and Poly I:C in squalene emulsion form (MPS). MPQ and MPS displayed greater adjuvancity in Th1 induction than DMT or MP did. Especially, BCG prime and subunit-MPS boost regimen significantly reduced the bacterial loads and pulmonary inflammation against Mtb K infection when compared to BCG-only vaccine at a chronic stage of TB disease. Collectively, our findings highlighted the importance of adjuvant components and formulation to induce the enhanced protection with an optimal Th1 response.

• Tuberculosis and Respiratory Diseases
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• v.75 no.1
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• pp.18-24
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• 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
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• v.53 no.2
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• pp.161-172
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• 2002

Background : To Investigate the association between bronchial anthracofibrosis (AF) and tuberculosis (TB), and the clinical utility of a polymerase chain reaction (PCR) on bronchial specimens for rapid diagno-sis of active pulmonary TB in patients with bronchial AF. Method : Thirty patients (25 women and 5 men ranging in age from 53 to 88), who were diagnosed with bronchial AF by a bronchoscopic exami-nation, were enrolled in this study. PCR targeting the IS6110 segment of Mycobacterium tuberculosis was performed on the bronchial wash fluid and anthracofibrotic bronchial tissue. The PCR results were compared with the bacteriological, histological, and clinical findings. Results : Eighteen of the 30 patients (60%) were associated with TB, nine of whom were confirmed as having active TB. The remaining 9 had a past history of TB. The sputum or bronchial aspirate AFB smear, culture, and histological findings were positive in 4 (13%), 9 (30%), and 5 (17%) patients, respectively. PCR of the AF tissue and bronchial wash fluid was positive in 5 (17%) and 11 (37%) of the 30 patients, respectively. PCR was more sensitive than the AFB smears for diagnosing pulmonary TB (22 % us 89 %, respectively, p<0.05). All 5 patients with positive AF tissue PCR results also had both histological findings and positive bronchial wash fluid PCR results. Of the 3 patients with positive PCR but negative bacteriological or histological results, 2 of these patients appeared to have active tuberculosis on a clinical basis. Conclusion: Although TB-PCR did not reveal an increased association between bronchial AF and TB compared with traditional methods, PCR on the bronchial wash fluid appears to be useful for the rapid diagnosis of pulmonary TB in patients with bronchial AF. TB-PCR on AF bronchial tissue itself did not yield additional benefits for diagnosing TB, which suggests that an AF lesion itself may not be an active or original site of the infection, but a secondary change of TB.

• Pediatric Infection and Vaccine
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• v.20 no.1
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• pp.17-27
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• 2013

Purpose: Recently, two tests are commercially available for the identification of latent tuberculosis infection (LTBI): tuberculin skin test (TST) and interferon-${\gamma}$ release assay (IGRA). Due to its false positiveness, TST tends to be preferred by IGRA until now. In our study, we simultaneously performed both TST and QuantiFERON$^{(R)}$-TB Gold In-Tube (QFT-GIT) and compared their results. Methods: TST and QFT-GIT were done for the diagnosis of LTBI among children who visited pediatric out-patient clinic at St. Vincent's Hospital, The Catholic University of Korea from February of 2007 to May of 2008. The study group was stratified into two groups in terms of whether there was intrafamilial contact or not. Results: Out of total 35 children, 29 were tuberculosis (TB)-exposed cases and the remainders were diagnosed as clinical pulmonary TB. Among these 29 children, TST was positive 38.9% (7/18) for the intrafamilial and 45.5% (5/11) for the nonintrafamilial, and at the same time, the result for QFT-GIT was positive 5.6% (1/18) and 9.1% (1/11), respectively which implies that TST was more sensitive than QFT-GIT. Among 29 TB-exposed cases, 26 initially went through TST and QFTGIT together on their first visit to out-patient clinic, and 15 continued the follow-up tests. Out of total 41 cases collected, the agreement (known as kappa value) was 0.063 which was relatively low. Including 6 cases with pulmonary TB who were all positive for TST and only 5 being positive for QFT-GIT, the final kappa value was 0.334. Conclusion: In our study, the agreement for TST and QFT-GIT was low, and the majorities were almost the cases of positive TST. In current situation with lacking a gold standard test and limited data on children to adolescents, this result is quite alarming that the recent trend tends to replace TST by QFT-GIT when diagnosing LTBI.

• Journal of Microbiology and Biotechnology
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• v.29 no.3
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• pp.489-499
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• 2019

Subunit vaccines are safer and more stable than live vaccines although they have the disadvantage of eliciting poor immune response. To develop a subunit vaccine, an effective delivery system targeting the key elements of the protective immune response is a prerequisite. In this study, oxidized carbon nanospheres (OCNs) were used as a subunit vaccine delivery system and tuberculosis (TB) was chosen as a model disease. TB is among the deadliest infectious diseases worldwide and an effective vaccine is urgently needed. The ability of OCNs to deliver recombinant Mycobacterium tuberculosis (Mtb) proteins, Ag85B and HspX, into bone marrow derived macrophages (BMDMs) and dendritic cells (BMDCs) was investigated. For immunization, OCNs were mixed with the two TB antigens as well as the adjuvant monophosphoryl lipid A (MPL). The protective efficacy was analyzed in vaccinated mice by aerosol Mtb challenge with a virulent strain of Mtb and the bacterial burdens were measured. The results showed that OCNs are highly effective in delivering Mtb proteins into the cytosol of BMDMs and BMDCs. Upon immunization, this vaccine formula induced robust Th1 immune response characterized by cytokine profiles from restimulated splenocytes and specific antibody titer. More importantly, enhanced cytotoxic $CD8^+$ T cell activation was observed. However, it did not reduce the bacteria burden in the lung and spleen from the aerosol Mtb challenge. Taken together, OCNs are highly effective in delivering subunit protein vaccine and induce robust Th1 and $CD8^+$ T cell response. This vaccine delivery system is suitable for application in settings where cell-mediated immune response is needed.

• Korean Journal of Veterinary Service
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• v.34 no.4
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• pp.321-331
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• 2011

Mycobacterium bovis, a member of the M. tuberculosis complex (MTC), is the causative agent of bovine tuberculosis. Detection of M. bovis and M. tuberculosis using conventional culture- and biochemical-based assays is time-consuming. Therefore, a simple and sensitive molecular assay for rapid detection would be of great help in specific situations such as faster diagnosis of bovine tuberculosis (bTB) infection in the abattoirs. We developed a novel multiplex real-time PCR assay which was applied directly to biological samples with evidence of bTB and it was allowed to differentiate between M. bovis and M. tuberculosis. The primers and TaqMan probes were designed to target the IS1081 gene, the multi-copy insertion element in the MTC and the 12.7-kb fragment which presents in M. tuberculosis, not in the M. bovis genome. The assay was optimized and validated by testing 10 species of mycobacteria including M. bovis and M. tuberculosis, and 10 other bacterial species such as Escherichia coli, and cattle lymph nodes (n=113). The tests identified 96.4% (27/28) as M. bovis from the MTC-positive bTB samples using conventional PCR for specific insertion elements IS1081. And MTC-negative bTB samples (n=85) were tested using conventional PCR and the real-time PCR. When comparative analyses were conducted on all bovine samples, using conventional PCR as the gold standard, the relative accuracy of real-time PCR was 99.1%, the relative specificity was 100%, and the agreement quotient (kappa) was 0.976. The detection limits of the real-time PCR assays for M. bovis and M. tuberculosis genomic DNA were 10 fg and 0.1 pg per PCR reaction, respectively. Consequently, this multiplex real-time PCR assay is a useful diagnotic tool for the identification of MTC and differentiation of M. bovis and M. tuberculosis, as well as the epidemiologic surveillance of animals slaughtered in abattoir.