• Clinical and Experimental Pediatrics
• /
• v.52 no.5
• /
• pp.519-528
• /
• 2009

Tuberculosis continues to cause an unacceptably high toll of disease and death among children worldwide. Whereas intense scientific and clinical research efforts into novel diagnostic, therapeutic, and preventive interventions have focused on tuberculosis in adults, childhood tuberculosis has been relatively neglected. However, children are particularly vulnerable to severe disease and death following infection, and those with latent infection become the reservoir for future transmission following disease reactivation in adulthood, fuelling future epidemics. Therefore, it is very important to understand the significance, diagnosis and treatment of latent tuberculous infection to decrease a future disease burden of tuberculosis. Unfortunately, these concept still have not fully implicated in Korean National Tuberculosis Control Program, it should be engaged and enforced as soon as possible.

• Tuberculosis and Respiratory Diseases
• /
• v.65 no.2
• /
• pp.79-90
• /
• 2008

국내에서 아직 잠복결핵 치료 대상 및 치료 방법에 대한 명확한 지침이 부족한 실정이며 이를 위해서는 잠복감염의 재활성화 혹은 새로운 감염이 어느 정도 결핵 발병의 원인이 되는지에 대한 연구가 선행되어야 한다. 그렇지만 발병의 위험이 높은 군을 선정하여 잠복결핵의 치료 대상으로 정하는 것이 타당할 것이며, 현재는 HIV 감염자, 전염성 결핵환자 가족 중 6세 미만의 아동, 중학생 및 고등학생에서의 집단 발병시 감염된 것으로 판정된 학생 및 종양괴사인자(tumor necrosis factor, TNF) 길항제 사용 예정인 잠복결핵 환자가 잠복결핵의 치료 대상으로 제한되어 있다. 향후에는 잠복결핵 치료 대상자의 확대가 필요할 것으로 생각되며, 치료방법 또한 isoniazid (INH) 단독 요법 이외에 rifampicin (RMP)을 포함하는 단기 요법의 사용도 고려하여야 하겠다. 현재 외국에서 잠복결핵의 치료법으로 권고되고 있는 것은 INH 6~9개월, RMP 4~6개월, INH/RMP 3개월 등이다. 과거부터 잠복결핵의 진단에 사용되어 온투베르쿨린 검사 외에 체외 인터페론감마 검사가 새로이 개발되면서 잠복결핵의 진단이 더 정확해진다면 이에 따라 잠복결핵 치료 방침도 수정될 가능성이 있으므로 새로운 검사법을 이용한 꾸준한 연구가 필요할 것이다.

• Korean Journal of Clinical Laboratory Science
• /
• v.50 no.1
• /
• pp.20-28
• /
• 2018

Tuberculosis (TB) is a bacterial infection disease caused by members of the species Mycobacterium tuberculosis (MTB) complex. Approximately one third of the world's population is infected with TB. In Korea, approximately 40,000 new patients are identified each year. Moreover, infections from non-tuberculous mycobacteria (NTM) have also increased. In the diagnosis of TB and NTM, traditional bacterial cultures are required for 3 to 4 weeks. Therefore, rapid and accurate diagnostic tests for TB and NTM are needed. To distinguish between TB and NTM, a range of diagnostic methods have been developed worldwide. In vitro diagnostic assays are constantly being developed to meet the increasing need for the rapid and accurate identification for TB and NTM. On the other hand, the performance evaluations of in vitro diagnostic reagents for TB and NTM are lacking. Recently, the Korea Food and Drug Administration (KFDA) issued a guideline for in vitro diagnostic reagents for MTB and NTM. Here, this study analyzed the performance of currently developed in vitro diagnostic reagents for TB and NTM in the US FDA. This analysis of US FDA approved molecular assays could serve as a useful reference for an evaluation of the reagent performance of TB and NTM.

• Tuberculosis and Respiratory Diseases
• /
• v.61 no.3
• /
• pp.239-247
• /
• 2006

Background: Culture filtrate proteins secreted by mycobacteria are thought to play an important role in inducing protective immunity and to develop new methods for diagnosing tuberculosis. Methods: A culture filtrate protein of M. avium that was strongly reactive with goat antiserum against M. intracellulare was constructed. Its homologous protein (TB-14) in M. tuberculosis was cloned, expressed and purified. The inductions of IFN-${\gamma}$ stimulated with $10{\mu}g$ of TB-14 recombinant protein and $10{\mu}g$ PPD were estimated by using whole bloods from seven PPD (-) subjects, seven PPD (+) healthy volunteers and nine tuberculosis patients. Results: M. avium culture filtrate protein was confirmed as a hypothetical protein that was termed contig 116. A novel 14-kDa recombinant protein (TB-14) of M. tuberculosis was composed of 148 amino acids, including 30 amino acids of the signal peptide, and it showed 78% homology with M. avium. In the PPD (+) healthy volunteers, recombinant TB-14 protein strongly induced the secretion of IFN-${\gamma}$ in whole blood cultures. Conclusion: These results suggest that TB-14 recombinant protein might play an important role in inducing cell-mediated immunity against tuberculosis. Furthermore, TB-14 protein antigen and its antiserum will be available for the development of new diagnostic tools for tuberculosis.

• Tuberculosis and Respiratory Diseases
• /
• v.60 no.2
• /
• pp.194-204
• /
• 2006

Background : Even though tuberculosis (TB) is still a major public concern in Korea, there is little data on the management of TB patients and its outcomes in the private sector. This study evaluated the status of TB treatment in the private sector. Methods : Sixteen-hundred-sixty-six TB patients who were notified in a private university hospital from 2001 to 2002 were enrolled in this study. The patients were divided into pulmonary ($TB_P$), extrapulmonary ($TB_E$), and combined ($TB_{P+E}$) groups, and were also divided into initial and retreatment groups. The clinical characteristics, diagnostic methods, treatment regimens, and outcomes were analyzed and compared. Results : The mean age of the 1,666 patients was 48.9 years and the male-to-female ratio was 1.3:1. The number of patients in the initial and retreatment groups of $TB_P$, and those of ($TB_E+TB_{P+E}$) were 809, 276, 480, 101, respectively. A bacteriological study was performed in 92.0% of cases, and a positive culture was confirmed in 58.1% and 31.7% of patients with TBP and ($TB_E+TB_{P+E}$), respectively (p<0.05). The AFB smear was positive in 45.4 % of the $TB_P$ patients. PCR was carried out in 60.4% of the ($TB_E+TB_{P+E}$) group. The MDR was detected in 14.0% of isolates. Overall, the treatment completion, default, and death rates were 70.2%, 13.5% and 1.9%, respectively. Conclusion : Even though the management of TB patients in a private hospital was satisfactory in terms of the national guidelines, the high default rate was is still a problem. Efforts to decrease the default rate either independently or in cooperation with the public sector will be needed.

• Tuberculosis and Respiratory Diseases
• /
• v.48 no.6
• /
• pp.853-869
• /
• 2000

Background : Following several decades of decline, the incidence of tuberculosis has recent1y begun to increase in many countries of this the control of this disease has been impeded by the emergence of multi-drug resistant tuberculosis (MDR-TB). The development of rapid diagnostic methods and effective new drugs are needed to control MDR-TB. One of the new drugs for MDR-TB is rifabutin (RBU) which has been known to be effective in some patients with MDR-TB. A few reports showed that some types of mutations of the rpoB gene, which were known to be present in 96-98% of rifampicin-resistant M. tuberculosis, were associated with the rifampicin-resistant but RBU-susceptible phenotype. This study was performed to investigate the correlation between RBU susceptibility and the patterns of rpoB gene mutations in Korean MDR-TB. Methods : Sixty-five clinical isolates of multi-drug resistant Mycobacterium tuberculosis, gathered from patients who visited the Asan Medical Center from July 1997 to June 1999, were investigated. Clinical responses to rifabutin-containing regimen were evaluated. An RBU susceptibility test and sequencing analysis of rpoB gene were performed, and the results were analyzed to confirm which mutations correlated with RBU-susceptible MDR-TB. Results : Fifty-three of 56 (95%) clinical isolates of MDR-TB had 60 mutations of the rpoB gene. The most frequent mutations were found at codon 531 (43%), and two mutations were combined in seven clinical isolates. Five of 53 (10%) clinical isolates showed the RBU-susceptible phenotype, and in them the characteristic patterns of point mutations were found at codon 509, 516, and 526. Conclusion : The frequency and pattern of mutations of the rpoB gene of Korean MDR-TB isolates were similar to those in western countries, where the prevalence of tuberculosis is low, but some show RBU-susceptible phenotypes. RBU-susceptible MDR-TB isolates showed the characteristic pattern of mutations of the rpoB gene which could be used to rapidly diagnose RBU susceptibility.

• Tuberculosis and Respiratory Diseases
• /
• v.42 no.6
• /
• pp.838-845
• /
• 1995

The determination of ADA(adenosine deaminase) activity in pleural fluid is useful in differental diagnosis of pleural effusion. The conventional method of determining ADA activity used by Giusti was influenced by contamination of ammonia. Additionally, because Giusti's method was mannual method a determining the ADA activities in sample, was not easily automated. In 1993, Oosthuizen HM with collegues developed simple kinetic method for determining ADA activity. It was reliable and suiable method for automation. In this study, we have measured ADA activity in 162 patients with various pleural effusion by Hitachi 747 autoanalyser using the Oosthuizen kinetic method for the purpuse of determination of new diagnostic cut-off value for the tuberculous effusion and evaluation of the correlation between the conventional method and new automated method. This new method of an enzymatic reaction involves 2, 6-dichlorophenolindophenol dye(DICP), adenosine, xanthine oxidase(XO), and nucleoside phosphorylase(NP). The results were as follows: 1) The mean pleural ADA activity of the tuberculous effusion was $52.53{\pm}16.43\;U/L$ and significantly higher than that of other groups(p<0.001). If the diagnostic cut-off value of pleural ADA activity for tuberculous effusion is above 30 U/L, the sensitivity is 96% and the specificity is 90%. 2) The mean pleural to serum ADA activity ratio of the tuberculous effusion was $2.29{\pm}0.96$ and it was also significantly higher than that of other pleural groups(p<0.001). If the diagnostic cut-off value of pleural to serum ADA activity ratio is 1.5, the sensitivity is 80% and the specificity is 88% in the diagnosis of tuberculous pleural effusion. 3) The new kinetic method is correlates well to Giuisti's conventional method(r=0.971). In conclusion, the new kinetic method described is easily automated and seems to be suitable for the routine determination of ADA activity.

• Tuberculosis and Respiratory Diseases
• /
• v.44 no.6
• /
• pp.1225-1233
• /
• 1997

Background : Cervical tuberculous lymphadenitis(CTL) is one of the most common extra-pulmonary tuberculosis. Recently overall incidence of pulmonary tuberculosis has decreased, but the incidence of tuberculous lymphadenitis has not decreased. Its duration of treatment is still controversial and the pathogenesis, prognosis and relationship with other site tuberculous are poorly published. So we did a retrograde study of 120 cases of confirmed CTL about its clinical manifestations. Method : All patients were applied fine needle aspiration(FNA) of palpable enlarged cervical lymph nodes and 114 patients were examined for AFB smear and 34 patients for TB culture with aspirated fluid. 57 patients were examined Mantoux test(5TU with PPD-S). With above methods, a total of 120 patients was diagnosed as having CTL. Results : 1) CTL is most prevalent in young women between the age of 20~30 years and the incidence of CTL in female is 2.5 times higher than that of male. It is located most commonly in the posterior cervical area. The most common presenting symptom is painless palpable enlarged cervical lymph nodes. 2) With FNA of enlarged cervical lymph nodes, the percentage of histopathological positivity is 82.3%. The percentage of AFB smear positivity is 38.6%, and that of TB culture positivity is 17.6%(p<0.001). 3) Pulmonary tuberculosis is noted in 79 cases(65.8%). And 42 cases(53.5%) of them had minimal pulmonary tuberculosis. In 14 cases(11.7%), other extrapulmonary tuberculosis coexsisted and pleural tuberculosis was most Common in the order. 4) CTL was treated with anti-tuberculous medication(first line drug) and median treatment duration was 18.5months. During treatment, the size of involved lymph nodes decreased gradually in 62 cases(75.8%), newly developed lymph nodes were found in 25 cases(30.4%), fluctuation formation in 22 cases(26.8%) and fistula formation in 14 cases(17.0%). Conclusion : CTL is prevalent in women between the age of 20~40 years and it involves posterior cervical area most commonly. CTL is treated with long-term anti-tuberculous chemotherapy. We think it is one manifestation of systemic disease and frequently coexisting with pulmonary tuberculosis. Despite anti-tuberculous chemotherapy, the size of involved lymph nodes was increased, new lymph nodes were developed or fluctuation and fistula formed in involved lymph nodes. After sufficient medication, when the patient felt pressure discomfort from enlarged lymph node or fistula was formed, we recommended total excision of involved lymph nodes.

• Tuberculosis and Respiratory Diseases
• /
• v.60 no.4
• /
• pp.404-411
• /
• 2006

Purpose : Multidrug-resistant tuberculosis (MDR-TB) is an emerging threat to human beings. However, there is little data on the current status of MDR-TB in Korea. This study investigated the current status of MDR-TB in Korea using a survey of all the data from drug susceptibility tests (DST) performed across the country over the last three years. Method : The DST results between Jan. 2000 and Dec. 2002 from 7 laboratories, which were in charge of all antituberculous DSTs across the country as of March 2002, were collected and analyzed to determine the actual number of drug-resistant or MDR-TB patients, annual trend, degree and pattern of resistance against anti-TB drugs, etc. Results : Six laboratories used the absolute concentration method for DST and one used the proportional method. 59, 940 tests had been performed over the 3 year study period. The number of DST performed annually was 18,071, 19,950, and 21,919 in 2000-2002, respectively. The number of resistant tuberculosis patients (resistant against at least one anti-TB drug) had increased by 16.9% from 6,338 in 2000 to 7,409 in 2002. The rate of resistant tuberculosis among all DST results was 35.1% in 2000, 34.5% in 2001, and 33.8% in 2002. The number of MDR-TB patients (resistant against at least both isoniazid and rifampin) showed an increasing trend (14.5%) from 3,708 in 2000 to 4,245 in 2002. Conclusion : Approximately 4,000 MDR-TB cases are newly identified by DST annually and the number is showing an increasing trend. This study suggests that in order to cope with the current MDR-TB situation, the DST methods will need to be standardized and more aggressive measures will be required.

• Tuberculosis and Respiratory Diseases
• /
• v.54 no.2
• /
• pp.178-190
• /
• 2003

Background : The committee of tuberculosis(TB) survey planning for the year 2000 decided to construct the Korean Tuberculosis Surveillance System (KTBS), based on a doctor's routine reporting method. The successful keys of the KTBS rely on the precision of the recorded TB notification forms. The purpose of this study was to determine that the accuracy of the TB notification form written at a private general hospital given to the corresponding health center and to improve the comprehensiveness of these reporting systems. Materials and Methods : 291 adult TB patients who had been diagnosed from August 2000 to January 2001, were enrolled in this study. The lists of TB notification forms were compared with the medical records and the various laboratory results; case characteristics, history of previous treatment, examinations for diagnosis, site of the TB by the international classification of the disease, and treatment. Results : In the list of examinations for a diagnosis in 222 pulmonary TB patients, the concordance rate of the 'sputum smear exam' was 76% but that of the 'sputum culture exam' was only 23%. Among the 198 cases of the sputum culture exam labeled 'not examined', 43(21.7%) cases proved to be true 'not examined', 70 cases(35.4%) were proven to be 'culture positive', and 85(43.0%) cases were proven to be 'culture negative'. In the list of examinations for a diagnosis in 69 extrapulmonary TB patients, the concordance rate of the 'smear exam other than sputum' was 54%. In the list of treatments, the overall concordance rate of the 'type of registration' in the TB notification form was 85%. Among the 246 'new' cases on the TB notification form, 217(88%) cases were true 'new' cases and 13 were proven to be 'relapse', 2 were proven to be 'treatment after failure', one was proven to be 'treatment after default', 12 were proven to be 'transferred-in' and one was proven to be 'chronic'. Among the 204 HREZ prescribed regimen, 172(84.3%) patients were taking the HREZ regimen, and the others were prescribed other drug regimens. Conclusion : Correct recording of the TB notification form at the private sectors is necessary for supporting the effective TB surveillance system in Korea.