• Tuberculosis and Respiratory Diseases
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• v.57 no.2
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• pp.101-117
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• 2004

현증 결핵환자가 감소하고, 면역억제환자가 증가하고 있는 국내 추세에서 잠복결핵(latent tuberculosis)의 진단 및 치료 지침이 필요한 실정이다. 그러나 결핵의 유병률, 발생률 그리고 비씨지 접종률 등이 외국과 다른 국내의 현실에서 현증이 없는 잠복결핵의 진단 및 치료에 대한 방침은 필연적으로 외국과 다를 수 밖에 없으며, 현 시점에 국내에서 이에 대한 자료가 불충분하여 국내의 환경에 적합한 근거 중심의 지침을 설정하기는 어려운 상황이다. 그러나 결핵의 기본 병태 생리를 근거로 하여 최소한 결핵균 감염 이후 결핵 발병의 위험성이 높은 대상 환자에서는 잠복결핵 진단을 위한 검사를 시행하여 치료 여부를 결정하여야 한다. 고위험군은 사람면역결핍바이러스(human immunodeficiency virus, HIV) 감염자, 장기이식환자, 면역억제제를 장기간 사용하는 환자, 6세 이하의 소아 중 최근 전염성 결핵환자 접촉자 등을 우선적으로 고려해야 한다. 미국은 발병 위험도의 고, 중, 저에 따라 투베르쿨린 검사(tuberculin skin test, Mantoux test)의 양성기준을 달리 하여 잠복결핵을 진단하고 있으나, 국내에는 아직 이에 대한 자료가 부족하므로 발병의 위험이 높은 상기 고위험군을 대상으로 하여 PPD RT-23 2TU (Tuberculin unit)를 이용한 피부반응검사에서 10mm이상의 경결(induration)이 생성되는 경우를 양성으로 정하고 추후 연구 결과에 따라 재조정이 필요하다. 그 동안은 투베르쿨린 검사 결과 5-10 mm 사이의 경결반응을 보이는 면역억제 환자에 대하여는 개별적으로 의사의 판단에 따라 잠복결핵의 진단 및 치료 여부를 결정한다. 그러나 면역억제제를 사용하는 등 결핵 발병의 고위험군에서는 피부반응검사상 음성이라도 과거 결핵 치료력이 없이 흉부사진상 명백하게 과거에 결핵을 앓은 흉터가 남아있는 경우(석회화된 1차 결핵 소견은 제외)에는 잠복결핵의 치료를 시행한다. 상기 잠복결핵의 진단 및 검사의 적응증은 최소한 시행하여야 할 경우를 나열한 것으로 이외의 환자에 대하여는 환경 및 대상에 따라 개별화되어야 한다. 치료제로는 isoniazid (INH) 9개월 매일 치료(최소 한 6개월 이상, HIV양성 환자인 경우는 9개월), rifa-mpicin (RFP) 4개월 치료 및 INH/RFP 3개월 매일 치료를 시행할 수 있다. 상기 치료가 어려운 경우에는 RFP/pyrazinamide (PZA) 2개월 매일 치료를 고려할 수 있으나 중증 간독성의 가능성에 대한 철저한 교육 및 추적검사가 필요하다. 향후 국내 환경의 변화 및 연구결과에 따라 추후 부족한 부분에 대한 지침의 재정립이 필요하다.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.66 no.1
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• pp.13-19
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• 2009

Background: The interferon-gamma assay is reported to have high sensitivity and specificity for making the diagnosis of latent tuberculosis infection. The clinical usefulness of this essay for detecting active tuberculosis has not fully defined. We evaluated the diagnostic value of the commercial interferon-gamma assay kit (QuantiFERONTB GOLD) for patients with suspected tuberculosis. Methods: From January to August 2007, we recruited 52 patients with suspected tuberculosis infection. We performed chest X-ray, sputum smear, culture, PCR and the QuantiFERON-TB GOLD test. Pleural fluid analysis and pleural biopsy were also done for the patients with pleural effusion. Results: Of the 52 patients we studied, 30 patients had a positive QuantiFERON-TB GOLD test result. 35 patients were finally diagnosed with active tuberculosis: twenty-five with a positive QuantiFERON-TB GOLD test and 10 with a negative QuantiFERON-TB GOLD test. The sensitivity of the QuantiFERON-TB GOLD test was 71.4% and the specificity was 64.7%. The positive predictive value was 0.83 and the negative predictive value was 0.50. There was no significant difference of any of the clinical and laboratory characteristics between the two groups of patients except the C-reactive protein (CRP) level. The CRP level was 29.2${\pm}$27.3 mg/dL in the pulmonary tuberculosis patients with a positive QuantiFERON-TB GOLD test and 72.9${\pm}$67.9 mg/dL in the patients with a negative QuantiFERON-TB GOLD test (p<0.05). Conclusion: The sensitivity and specificity of the QuantiFERON-TB GOLD test were inadequate for making the diagnosis of active tuberculosis. We suggest that the QuantiFERON-TB GOLD test should not be used by itself to exclude the diagnosis of active tuberculosis. The relationship of the QuantiFERON-TB GOLD test and the CRP level in patients with TB would be further investigated.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7415-7419
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• 2013

The diagnosis of latent Mycobacterium tuberculosis infection (LTBI) is recommended in hematological malignancy patients and before hematopoietic stem cell transplantation (Guidelines for the prevention and management of infectious complications of solid organ transplantation, 2004). Compared to traditional methods such as tuberculin skin test (TST), T-SPOT.TB has been shown to be more specific. In the present study we enrolled 536 patients for whom T-SPOT.TB was performed, among which 295 patients also received the TST test. The agreement (79%) between T-SPOT.TB and TST was poor (x=0.274, P<0.001). The patients with positive T-SPOT.TB results numbered 62 (11.6%), in which only 20 (48.8%) of the 41 receiving the TST test had positive results. A majority of the patients with T-SPOT.TB positive results had some other evidence ofTB, such as TB history, clinical symptoms and an abnormal chest CT scan. Active TB was found in 9 patients, in which 2 had negative TST results. We followed up the patients and no one developed active TB. Our study suggested that the T-SPOT.TB may be more useful for screening LTBI and active TB in hematological malignancy patients and hematopoietic stem cell transplant recipients than the TST test.

• 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.

• 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.83 no.3
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• pp.218-227
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• 2020

Background: The national Public-Private Mix (PPM) tuberculosis (TB) control project provides for the comprehensive management of TB patients at private hospitals in South Korea. Surveillance and monitoring of TB under the PPM project are essential toward achieving TB elimination goals. Methods: TB is a nationally notifiable disease in South Korea and is monitored using the surveillance system. The Korea Centers for Disease Control and Prevention quarterly generates monitoring indicators for TB management, used to evaluate activities of the PPM hospitals by the central steering committee of the national PPM TB control project. Based on the notification date, TB patients at PPM hospitals were enrolled in each quarter, forming a cohort, and followed up for at least 12 months to identify treatment outcomes. This report analyzed the dataset of cohorts the first quarter of 2016 through the fourth quarter of 2017. Results: The coverage of sputum, smear, and culture tests among the pulmonary TB cases were 92.8% and 91.5%, respectively. The percentage of positive sputum smear and culture test results were 30.7% and 61.5%, respectively. The coverage of drug susceptibility tests among the culture-confirmed cases was 92.8%. The treatment success rate among the smear-positive drug-susceptible cases was 83.2%. The coverage of latent TB infection treatment among the childhood TB contacts was significantly higher than that among the adult contacts (85.6% vs. 56.0%, p=0.001). Conclusion: This is the first official report to analyze monitoring indicators, describing the current status of the national PPM TB control project. To sustain its effect, strengthening the monitoring and evaluation systems is essential.

• Pediatric Infection and Vaccine
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• v.21 no.3
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• pp.191-198
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• 2014

Purpose: The aim of this study was to evaluate the clinical manifestations, contact history, and status of tuberculosis contact investigations in school-age children and adolescents with pulmonary tuberculosis (TB) at two centers. Methods: This study was conducted with 54 patients in the age ranging from 10 to 18 years, who were diagnosed with pulmonary TB at the Pusan National University Hospital and Pusan National University Children's Hospital, January 2008 to December 2012. We retrospectively reviewed the medical records of the patients. Results: The median age of the patients was 16 years old; 11 patients were aged 10 to 14 and 43 patients were aged 15 to 18. Among 54 patients, 19 had history of contact with pulmonary TB, 10 had contact with house members (household), and remaining 9 had contact with classmates (non-household). One out of 10 patients who had household contacts and 6 out of 9 patients who had non-household contacts were evaluated with contact investigation after the exposure to pulmonary TB. Among 7 patients who were evaluated with contact investigation, 3 were diagnosed with active pulmonary TB, 1 had latent tuberculosis infection (LTBI), and 3 had no evidence of TB or LTBI. The median period of diagnosis after the exposure to active pulmonary TB was 2 years in patients with household contacts and 0.23 years in patients with non-household contacts. Conclusion: This study suggested that if the contact investigation conducted properly, it would be helpful for early diagnosis and prevention of pulmonary TB.

• Tuberculosis and Respiratory Diseases
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• v.60 no.1
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• pp.38-43
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• 2006

Background : Even though two-month rifampicin (RMP, R) and pyrazinamide (PZA, P) treatment has some advantages over isoniazid (INH, H) treatment for latent tuberculosis infection (LTBI), it was withdrawn from the list of treatment regimens for LTBI because of reported cases of severe hepatotoxicity. The purpose of this study was to estimate the frequency of hepatotoxicity of RMP and PZA treatment excluding INH in a Korean population. Method : TIn order to recruit patients who were prescribed RMP and PZA excluding INH, 256 INH-resistant tuberculosis patients were investigated through retrospective medical record analysis. A standard four-drug regimen was changed to a RMP/PZA-containing regimen excluding INH in 64 patients (RZ+ group). In the same study period, 146 patients who were prescribed an INH/RMP/PZA-containing standard regimen were randomly selected as a control (HRZ+ group). Clinical characteristics including liver diseases and the frequency of drug-induced hepatitis were compared between the RZ+ and HRZ+ groups. Result : The mean age of patients in the RZ+ group was 50.2 (${\pm}16.2$) and the male-to-female ratio was 36:28. The frequency of underlying liver diseases was 10.9% (7/64), which was not significantly different from that of the HRZ+ group (4.1%, 6/146). Even though the treatment duration of RZ+ ($5.5{\pm}4.8months$) was longer that than that of HRZ+ ($2.7{\pm}2.3months$), the frequency of toxic hepatitis was not significantly different between RZ+ and HRZ+ groups, 3.5% (2/57) and 7.1% (10/140), respectively. Conclusion : Hepatotoxicity was mild and occurred in a minor proportion of patients in a Korean population prescribed an RMP/PZA-containing regimen. A future prospective study including more patients is needed.