• Pediatric Infection and Vaccine
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• v.15 no.1
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• pp.52-58
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• 2008

Purpose : Whole blood interferon-$\gamma$ assay was developed and many studies showed its usefulness in diagnosing tuberculosis (TB) including latent tuberculosis infection (LTBI). However, assessment in children has been limited. This study was undertaken to evaluate the usefulness of QuantiFERON-TB Gold for the diagnosis of LTBI in children exposed to pulmonary TB. Methods : Children who visited Seoul National University Bundang Hospital with a history of TB exposure were enrolled from January 2006 to December 2007. They were evaluated with chest x-rays, tuberculin skin test (TST) and QuantiFERON-TB Gold test. TST was retested 3 months later for those with initial negative reactivity. Definition of LTBI was made on the basis of the TST reactivity. Results : Among the 103 children with a history of TB exposure, 49 children were tested with chest x-ray, TST, and QuantiFERON-TB Gold. Twenty-two were males. Median age was 7.5 years (range; 3 months to 14.7 years). According to TST reactivity, LTBI was in 8 (19%), no infection was in 21 (50%), possible LTBI was in 13 (31%). QuantiFERON-TB Gold test was positive in 5 of the 49 subjects (10%); 3 of the 13 subjects (23.1%) in unknown status, 1 of the 8 subjects (13%) in LTBI, and 1 of the 21 subjects (5%) without infection. The agreement between the QuantiFERON-TB Gold and the TST was poor (${\kappa}=0.101$). Conclusion : QuantiFERON-TB Gold showed poor sensitivity for the diagnosis of LTBI in children with exposure to TB. QuantiFERON-TB Gold alone does not seem to be useful in the diagnosis of LTBI in children.

• Tuberculosis and Respiratory Diseases
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• v.59 no.4
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• pp.406-412
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• 2005

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. Methods : 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 ($1^{st}$). The TST was repeated two months later ($2^{nd}$), and the $IFN-{\gamma}$ assays were repeated two ($2^{nd}$) and four months ($3^{rd}$) 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 $3.1{\pm}5.4mm$ (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 $2^{nd}$ and $3^{rd}$ QFT were carried out in 23 and 25 all-negative subjects, respectively, and all showed negative results. The $2^{nd}$ 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.

• Pediatric Infection and Vaccine
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• v.23 no.1
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• pp.18-24
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• 2016

Purpose: There is a the great diagnostic challenge in pediatric tuberculosis especially in high burden setting. The purpose of this preliminary study is to evaluate the agreement between tuberculin skin test (TST) and interferon-gamma release assay (IGRA) including T-SPOT$^{(R)}$.TB and QuantiFERON$^{(R)}$-TB Gold (QFT-G) in Korean children. Method: This retrospective study included children and adolescents who visited to Asan Medical Center to evaluate tuberculosis infection using at least two assays of TST, T-SPOT.TB and QFT-G, from January 2014 to April 2015. Results: A total of 20 patients were included, whose median age was 13.3 years (range, 3.8-18.1 years), and all of them had history of BCG vaccination. Eleven patients had underlying diseases including 7 patients with immunosuppressant medication. The concordance rate between T-SPOT.TB and QFT-G was 90%. However, the concordance rate between TST and T-SPOT.TB was 50%, and between TST and QFT-G was 42.9%. Specificity for the diagnosis of tuberculosis infection of T-SPOT.TB, QFT-G, and TST was 93.3%, 86.7%, and 58.3%, respectively. Conclusions: Although there was a discrepancy between TST and IGRA to diagnose tuberculosis, agreement between T-SPOT.TB and QFT-G was relatively high. Further prospective study to validate the clinical usefulness of each assay for immunologic evidence of tuberculosis infection in Korean children will be mandatory.

• Tuberculosis and Respiratory Diseases
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• v.56 no.3
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• pp.268-279
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• 2004

Background : The tuberculin skin test has been used to diagnose latent tuberculosis infection, but is not widely used to diagnose or exclude pulmonary tuberculosis. The objective of this study was to evaluate the diagnostic utility of the tuberculin test in diagnosing and excluding pulmonary tuberculosis, and differentiating pulmonary tuberculosis from nontuberculous mycobacteria (NTM) pulmonary disease, when a sputum acid-fast bacilli (AFB) smear was positive. Material and Methods : From October 2002 to August 2003, among all the inpatients of the Division of Pulmonary and Critical Care Medicine at Samsung Medical Center, 258 patients with clinical suspicion of pulmonary tuberculosis were enrolled and underwent a tuberculin test. Results : 156 males and 102 females were included, with a mean age of 57.5 years. The final diagnoses included lung cancer in 89 cases (34.5%), pulmonary tuberculosis in 59 cases (22.9%), bacterial pneumonia in 33 cases (12.8%) and NTM pulmonary disease in 24 cases (9.3%). The positive tuberculin test rate was higher in the tuberculosis than non-tuberculosis group; 81.4 (48/59) vs. 42.4% (81/199). (p<0.001). In 208 patients with a negative sputum AFB smear, the result of the tuberculin test was positive in 69.4% (25/36) of the tuberculosis group and in 44.8% (77/172) of the non-tuberculosis group (p=0.007), so a positive result of the tuberculin test could predict pulmonary tuberculosis with 69.4% sensitivity, 55.2% specificity, a 24.5% positive predictive value and a 89.6% negative predictive value. In 50 patients with a positive sputum AFB smear, the positive rates of the tuberculin test were 83.9% (26/31) in tuberculosis group and 21.1% (4/19) in NTM pulmonary disease group (p<0.001), so a positive result of the tuberculin skin test could predict pulmonary tuberculosis with 83.9% sensitivity, 78.9% specificity, a 86.7% positive predictive value and a 75.0% negative predictive value. Conclusion : The tuberculin test could be useful in excluding pulmonary tuberculosis when the sputum AFB smear is negative, and to differentiate pulmonary tuberculosis from NTM pulmonary disease when the sputum AFB smear is positive.

• Tuberculosis and Respiratory Diseases
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• v.70 no.2
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• pp.125-131
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• 2011

Background: The clinical manifestation of $M.$ $tuberculosis$ infection ranges from asymptomatic latent infection, to focal forms with minimal symptoms and low bacterial burdens, and finally to advanced tuberculosis (TB) with severe symptoms and high bacillary loads. We investigated the diagnostic sensitivity of the whole-blood interferon-${\gamma}$ release assay according to the wide spectrum of clinical phenotypes. Methods: In patients diagnosed with active TB that underwent $QuantiFERON^{(R)}$ (QFT) testing, the QFT results were compared with patients known to be infected with pulmonary tuberculosis (P-TB) and extra-pulmonary TB (EP-TB). In addition, the results of the QFT test were further analyzed according to the radiographic extent of disease in patients with P-TB and the location of disease in patients with EP-TB. Results: There were no statistical differences in the overall distribution of QFT results between 177 patients with P-TB and 84 patients with EP-TB; the positive results of QFT test in patients with P-TB and EP-TB were 70.1% and 64.3%, respectively. Among patients with P-TB, patients with mild extents of disease showed higher frequency of positive results of QFT test than that of patients with severe form (75.2% vs. 57.1%, respectively; p=0.043) mainly due to an increase of indeterminate results in severe P-TB. Patients with TB pleurisy showed lower sensitivity by the QFT test than those with tuberculous lymphadenitis (48.8% vs. 78.8%, respectively; p=0.019). Conclusion: Although QFT test showed similar results between overall patients with P-TB and EP-TB, individual sensitivity was different according to the radiographic extent of disease in P-TB and the location of disease in EP-TB.

• Tuberculosis and Respiratory Diseases
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• v.39 no.2
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• pp.172-175
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• 1992

Giant cell tumor is the second most common benign tumor of the bone. But, the incidence in the ribs is rare. Clinical features of giant cell tumor may vary markedly from latent to very aggressive. Recently, we experienced clinically aggressive form of giant cell tumor in the right 2nd rib and report this case with reviewing the articles of giant cell tumor.

• Tuberculosis and Respiratory Diseases
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• v.71 no.3
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• pp.172-179
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• 2011

Background: Statins can regulate the production of pro-inflammatory cytokines and inhibit MMP production or activation in a variety of types of cells. This study evaluated whether statins would inhibit MMP release from human lung fibroblasts, which play a major role in remodeling processes. Methods: This study, using an in-vitro model (three-dimensional collagen gel contraction system), evaluated the effect of cytokines (tumor necrosis factor-${\alpha}$, TNF-a and interleukin-$1{\beta}$, IL-1b) on the MMP release and MMP activation from human lung fibroblasts. Collagen degradation induced by cytokines and neutrophil elastase (NE) was evaluated by quantifying hydroxyproline. Results: In three-dimensional collagen gel cultures (3D cultures) where cytokines (TNF-a and IL-1b) can induce the production of MMPs by fibroblasts, it was found that simvastatin inhibited MMP release. In 3D cultures, cytokines together with NE induced collagen degradation and can lead to activation of the MMP, which was inhibited by simvastatin. Conclusion: Simvastatin may play a role in regulating human lung fibroblast functions in repair and remodeling processes by inhibiting MMP release and the conversion from the latent to the active form of MMP.

• Clinical and Experimental Pediatrics
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• v.51 no.9
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• pp.971-976
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• 2008

Purpose : Surveillance for detecting and managing latent tuberculosis infection (LTBI) is a key component of tuberculosis control. The classic surveillance tool, the tuberculin skin test (TST), may have some limitations when used in the Bacillus Calmette-$Gu{\acute{e}}rin$ (BCG)-vaccinated population. The object was to perform a blood test $QuantiFERON^{(R)}$-TB Gold In Tube (QFT-G IT) based on the detection of interferon-$\gamma$ ($IFN-{\gamma}$) released by T cells in response to Mycobacterium tuberculosis-specific antigens, and to compare the efficacy of this new diagnostic tool for LTBI with that of TST. Methods : For six months, between October 1, 2006 and April 30, 2007, data were collected from 111 patients under 15 years of age at Severance Children's Hospital. TST and QFT-G IT tests were performed with children with or without contact histories of tuberculosis. In addition to these tests, we examined comparative data from 29 adults who had tuberculosis, to detect false negative rates in the QFT-G IT method. Results : Thirty-three children had household contact histories. In this group, 15% and 42% of cases were found to be positive using the QFT-G IT assay and TST, respectively. Agreement was low between these two tests (${\kappa}=0.39$). In the adult active tuberculosis group, the QFT-G IT false negative rate defined as a positive culture and a negative QFT-G IT result was 12.5%. Conclusion : In diagnosing LTBI in children, the usefulness of a whole-blood $IFN-{\gamma}$ assay employing TB-specific antigens will be revealed only by examining additional longitudinal clinical data; this study serves as a starting point in that process.

• 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.

• 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.