• Tuberculosis and Respiratory Diseases
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• v.42 no.3
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• pp.277-294
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• 1995

Background: The prevalence of tuberculosis in Korea decreased remarkably for the past 30 years, while the incidence of disease caused by mycobacteria other than tuberculosis is unknown. Korean Academy of Tuberculosis and Respiratory Diseases performed national survey to estimate the incidence of mycobacterial diseases other than tuberculosis in Korea. We analyzed the clinical data of confirmed cases for the practice of primary care physicians and pulmonary specialists. Methods: The period of study was from January 1981 to October 1994. We collected the data retrospectively by correspondence with physicians in the hospitals that referred the specimens to Korean Institute of Tuberculosis, The Korean National Tuberculosis Association for the detection of mycobacteria other than tuberculosis. In confirmed cases, we obtained the records for clinical, laboratory and radiological findings in detail using protocols. Results: 1) Mycobacterial diseases other than tuberculosis were confirmed that 1 case was in 1981, 2 cases in 1982, 4 cases in 1983, 2 cases in 1984, 5 cases in 1985, 1 case in 1986, 3 cases in 1987, 1 case in 1988, 6 cases in 1989, 9 cases in 1990, 14 cases in 1990, 10 cases in 1992, 4 cases in 1993, and 96 cases in 1994. Cases since 1990 were 133 cases(84.2%) of a total. 2) Fifty seven percent of patients were in the age group of over 60 years. The ratio of male to female patients was 2.6:1. 3) The distribution of hospitals in Korea showed that 61 cases(38.6%) were referred from Double Cross Clinic, 42 cases(26.6%) from health centers, 21 cases(13.3%) from tertiary referral hospitals, 15 cases(9.5%) from secondary referral hospitals, and 10 cases(6.3%) from primary care hospitals. The area distribution in Korea revealed that 98 cases(62%) were in Seoul, 17 cases(10.8%) in Gyeongsangbuk-do, 12 cases(7.6%) in Kyongki-do, 8 cases(5.1%) in Chungchongnam-do, each 5 cases(3.2%) in Gyeongsangnam-do and Chungchongbuk-do, 6 cases(3.8%) in other areas. 4) In the species of isolated mycobacteria other than tuberculosis, M. avium-intracellulare was found in 104 cases(65.2%), M. fortuitum in 20 cases(12.7%), M. chelonae in 15 cases(9.5%), M. gordonae in 7 cases(4.4%), M. terrae in 5 cases(3.2%), M. scrofulaceum in 3 cases(1.9%), M. kansasii and M. szulgai in each 2 cases(1.3%), and M. avium-intracellulare coexisting with M. terrae in 1 case(0.6%). 5) In pre-existing pulmonary diseases, pulmonary tuberculosis was 113 cases(71.5%), bronchiectasis 6 cases(3.8%), chronic bronchitis 10 cases(6.3%), and pulmonary fibrosis 6 cases(3.8%). The timing of diagnosis as having pulmonary tuberculosis was within 1 year in 7 cases(6.2%), 2~5 years ago in 32 cases(28.3%), 6~10 years ago in 29 cases(25.7%), 11~15 years ago in 16 cases(14.2%), 16~20 years ago in 15 cases (13.3%), and 20 years ago in 14 cases(12.4%). Duration of anti-tuberculous treatment was within 3 months in 6 cases(5.3%), 4~6 months in 17 cases(15%), 7~9 months in 16 cases(14.2%), 10~12 months in 11 cases(9.7%), 1~2 years in 21 cases(18.6%), and over 2 years in 8 cases(7.1%). The results of treatment were cure in 44 cases(27.9%) and failure in 25 cases(15.8%). 6) Associated extra-pulmonary diseases were chronic liver disease coexisting with chronic renal failure in 1 case(0.6%), diabetes mellitus in 9 cases(5.7%), cardiovascular diseases in 2 cases(1.3%), long-term therapy with steroid in 2 cases(1.3%) and chronic liver disease, chronic renal failure, colitis and pneumoconiosis in each 1 case(0.6%). 7) The clinical presentations of mycobacterial diseases other than tuberculosis were 86 cases (54.4%) of chronic pulmonary infections, 1 case(0.6%) of cervical or other site lymphadenitis, 3 cases(1.9%) of endobronchial tuberculosis, and 1 case(0.6%) of intestinal tuberculosis. 8) The symptoms of patients were cough(62%), sputum(61.4%), dyspnea(30.4%), hemoptysis or blood-tinged sputum(20.9%), weight loss(13.3%), fever(6.3%), and others(4.4%). 9) Smear negative with culture negative cases were 24 cases(15.2%) in first examination, 27 cases(17.1%) in second one, 22 cases(13.9%) in third one, and 17 cases(10.8%) in fourth one. Smear negative with culture positive cases were 59 cases(37.3%) in first examination, 36 cases (22.8%) in second one, 24 cases(15.2%) in third one, and 23 cases(14.6%) in fourth one. Smear positive with culture negative cases were 1 case(0.6%) in first examination, 4 cases(2.5%) in second one, 1 case (0.6%) in third one, and 2 cases(1.3%) in fourth one. Smear positive with culture positive cases were 48 cases(30.4%) in first examination, 34 cases(21.5%) in second one, 34 cases(21.5%) in third one, and 22 cases(13.9%) in fourth one. 10) The specimens isolated mycobacteria other than tuberculosis were sputum in 143 cases (90.5%), sputum and bronchial washing in 4 cases(2.5%), bronchial washing in 1 case(0.6%). 11) Drug resistance against all species of mycobacteria other than tuberculosis were that INH was 62%, EMB 55.7%, RMP 52.5%, PZA 34.8%, OFX 29.1%, SM 36.7%, KM 27.2%, TUM 24.1%, CS 23.4%, TH 34.2%, and PAS 44.9%. Drug resistance against M. avium-intracellulare were that INH was 62.5%, EMB 59.6%, RMP 51.9%, PZA 29.8%, OFX 33.7%, SM 30.8%, KM 20.2%, TUM 17.3%, CS 14.4%, TH 31.7%, and PAS 38.5%. Drug resistance against M. chelonae were that INH was 66.7%, EMB 66.7%, RMP 66.7%, PZA 40%, OFX 26.7%, SM 66.7%, KM 53.3%, TUM 53.3%, CS 60%, TH 53.3%, and PAS 66.7%. Drug resistance against M. fortuitum were that INH was 65%, EMB 55%, RMP 65%, PZA 50%, OFX 25%, SM 55%, KM 45%, TUM 55%, CS 65%, TH 45%, and PAS 60%. 12) The activities of disease on chest roentgenogram showed that no active disease was 7 cases(4.4%), mild 20 cases(12.7%), moderate 67 cases(42.4%), and severe 47 cases(29.8%). Cavities were found in 43 cases(27.2%) and pleurisy in 18 cases(11.4%). 13) Treatment of mycobacterial diseases other than tuberculosis was done in 129 cases(81.7%). In cases treated with the first line anti-tuberculous drugs, combination chemotherapy including INH and RMP was done in 86 cases(66.7%), INH or RMP in 30 cases(23.3%), and not including INH and RMP in 9 cases(7%). In 65 cases treated with the second line anti-tuberculous drugs, combination chemotherapy including below 2 drugs were in 2 cases(3.1%), 3 drugs in 15 cases(23.1%), 4 drugs in 20 cases(30.8%), 5 drugs in 9 cases(13.8%), and over 6 drugs in 19 cases (29.2%). The results of treatment were improvement in 36 cases(27.9%), no interval changes in 65 cases(50.4%), aggravation in 4 cases(3.1%), and death in 4 cases(3.1%). In improved 36 cases, 34 cases(94.4%) attained negative conversion of mycobacteria other than tuberculosis on cultures. The timing in attaining negative conversion on cultures was within 1 month in 2 cases(1.3%), within 3 months in 11 cases(7%), within 6 months in 14 eases(8.9%), within 1 year in 2 cases(1.3%) and over 1 year in 1 case(0.6%). Conclusion: Clinical, laboratory and radiological findings of mycobacterial diseases other than tuberculosis were summarized. This collected datas will assist in the more detection of mycobacterial diseases other than tuberculosis in Korea in near future.

• Journal of Microbiology and Biotechnology
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• v.29 no.8
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• pp.1221-1229
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• 2019

Mycobacterium tuberculosis, a causative pathogen of tuberculosis (TB), still threatens human health worldwide. To find a novel drug to eradicate this pathogen, we tested taurine-5-bromosalicylaldehyde Schiff base (TBSSB) as an innovative anti-mycobacterial drug using Mycobacterium smegmatis as a surrogate model for M. tuberculosis. We investigated the antimicrobial activity of TBSSB against M. smegmatis by plotting growth curves, examined the effect of TBSSB on biofilm formation, observed morphological changes by scanning electron microscopy and transmission electron microscopy, and detected differentially expressed proteins using two-dimensional gel electrophoresis coupled with mass spectrometry. TBSSB inhibited mycobacterial growth and biofilm formation, altered cell ultrastructure and intracellular content, and inhibited cell division. Furthermore, M. smegmatis adapted itself to TBSSB inhibition by regulating the metabolic pathways and enzymatic activities of the identified proteins. NDMA-dependent methanol dehydrogenase, NAD(P)H nitroreductase, and amidohydrolase AmiB1 appear to be pivotal factors to regulate the M. smegmatis survival under TBSSB. Our dataset reinforced the idea that Schiff base-taurine compounds have the potential to be developed as novel anti-mycobacterial drugs.

• Tuberculosis and Respiratory Diseases
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• v.53 no.5
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• pp.497-509
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• 2002

Background : The mechanisms through which cellular activation results in intracellular mycobacterial killing is only partially understood. However, in vitro studies of human immunity to Mycobacterium tuberculosis have been largely modeled on the work reported by Crowle, which is complicated by several factors. The whole blood culture is simple and allows the simultaneous analysis of the relationship between bacterial killing and the effect of effector cells and humoral factors. In this study, we attempted to determine the extent to which M. tuberculosis is killed in a human whole blood culture and to explore the role of the host and microbial factor in this process. Methods : The PPD positive subject were compared to the umbilical cord blood and patients with tuberculosis, diabetes and lung cancer. The culture is performed using heparinized whole blood diluted with a culture medium and infected with a low number of M. avium or M. tuberculosis $H_{37}Ra$ for 4 days by rotating the culture in a $37^{\circ}C$, 5% $CO_2$ incubator. In some experiments, methlprednisolone- or pentoxifyline were used to inhibit the immune response. To assess the role of the T-cell subsets, CD4+, CD8+ T-cells or both were removed from the blood using magnetic beads. The ${\Delta}$ log killing ratio was defined using a CFU assay as the difference in the log number of viable organisms in the completed culture compared to the inoculum. Results : 1. A trend was noted toward the improved killing of mycobacteria in PPD+ subjects comparing to the umbilical cord blood but there was no specific difference in the patients with tuberculosis, diabetes and lung cancer. 2. Methylprednisolone and pentoxifyline adversely affected the killing in the PPD+ subjects umbilical cord blood and patients with tuberculosis. 3. The deletion of CD4+ or CD8+ T-lymphocytes adversely affected the killing of M. avium and M. tuberculosis $H_{37}Ra$ by PPD+ subjects. Deletion of both cell types had an additive effect, particularly in M. tuberculosis $H_{37}Ra$. 4. A significantly improved mycobacterial killing was noted after chemotherapy in patients with tuberculosis and the ${\Delta}$ logKR continuously decreased in a 3 and 4 days of whole blood culture. Conclusion : The in vitro bactericidal assay by human whole blood culture model was settled using a CFU assay. However, the host immunity to M. tuberculosis was not apparent in the human whole blood culture bactericidal assay, and patients with tuberculosis showed markedly improved bacterial killing after anti-tuberculous chemotherapy compared to before. The simplicity of a whole blood culture facilitates its inclusion in a clinical trial and it may have a potential role as a surrogate marker in a TB vaccine trial.

• Tuberculosis and Respiratory Diseases
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• v.79 no.3
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• pp.153-157
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• 2016

Background: Vitamin D is known to have diverse effects on various systems in the body. There is evidence to suggest that a link exists between the serum vitamin D status and tuberculosis. The present study was designed to assess the alterations in serum 25-hydroxyvitamin D levels in newly diagnosed sputum acid fast bacilli (AFB) positive pulmonary tuberculosis patients and to study the association, if any, between serum vitamin D levels and different levels of sputum smear positivity. Methods: Serum 25-hydroxyvitamin D levels were estimated in 65 sputum AFB positive pulmonary tuberculosis patients and 65 age and gender-matched healthy controls. Results: The levels of serum 25 hydroxy-vitamin D in tuberculosis patients were not statistically different from the levels of serum 25 hydroxy-vitamin D in healthy controls. However, among patients with pulmonary tuberculosis, there was a significant negative correlation between the levels of serum 25 hydroxy-vitamin D and levels of sputum positivity. Conclusion: Serum vitamin D levels negatively correlates with bacterial load in patients with active pulmonary tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.57 no.2
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• pp.125-131
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• 2004

Tuberculosis (TB) remains an enormous global health problem, and a new vaccine against TB more potent than the current inadequate BCG vaccine is urgently needed. We constructed three recombinant Mycobacterium bovis BCG (rBCG) strains over-expressing antigen (Ag) 85A, Ag85B, or both of M. tuberculosis using their own promoter and secretory sequence, or hsp60 promoter. SDS-PAGE analysis of rBCG proteins showed overexpression of Ag85A and Ag85B proteins in higher level than of those in their parental strain of BCG. In addition, rBCG(rBCG/B.FA) over-expressing Ag85A and Ag85B induced strong IFN-${\gamma}$ production in splenocytes. However, there was no significant difference in protective efficacy between rBCG and their parental BCG strain. In this study, therefore, rBCG over-expressing Ag85A, Ag85B, or both failed to show enhanced protection against M. tuberculosis infection in a mouse model.

• Tuberculosis and Respiratory Diseases
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• v.48 no.3
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• pp.308-314
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• 2000

Background : DNA fingerprinting of Mycobacterium tuberculosis with RFLP is a very useful tool for deciphering the molecular epidemiology of tuberculosis. An international comparison of the RFLP pattern became possible with the proposal to standardize RFLP methodology using Pvu-II restricted IS-6110, and the comparison has noted some predominance of RFLP pattern in East Asia. The RFLP patterns of tuberculosis strains collected at SNUH was studied and was compared with other strains from East Asia. Method : Fifty strains of M. tuberculosis were isolated from patients who visited 'or were admitted to the SNUH in 1998. Some isolates belonging to the Beijing family were also received. After the extraction of DNA from M. tuberculosis isolates, the chromosomal DNAs were digested with Pvu-II and analyzed by the Southern blot method with DNA probe to IS6110. Result : Six strains belonged to the Beijing family. The RFLP patterns of other 9 strains were similar to each other. No statistically significant endobronchial tuberculosis, presence of underlying disease. and the province of residence were found. Conclusion : Few groups of M. tuberculosis strains from SNUH showed similar RFLP patterns, but their clinical implications are not yet clear.

• Tuberculosis and Respiratory Diseases
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• v.38 no.2
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• pp.99-107
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• 1991

Drug resistance of M. tuberculosis has been investigated with isolates from patients screened out of the sample population of the nationwide tuberculosis prevalence surveys or from the routine cultures. The results showed a close inverse relationship between prevalence of drug resistance and efficiency of the past or current treatment regimens of NTP. Individual drug resistance also showed a close relationship with the extent of use of the relevant drugs. Drug resistance was found in 38.0% of M. tuberculosis isolates from patients found in 1965 survey and remained unchanged until it increased upto 48.0% in 1980 survey. The resistance prevalence, however, dropped to 30.8% in 1985 and further to 25.3% in 1990 survey. Such decrease was fairly well coincided with a continuous increase of the treatment efficiency (from 60% in 1984 to 77% in 1989) in 1980s. Initial drug resistance also showed a similar trend, namely 26.2% in 1965, 23.9% in 1970, 20.1% in 1975, 30.6% in 1980, 17.4% in 1985, and 15.0% in 1990. The similar figures were observed in M. tuberculosis isolates from patients diagnosed in the routine services. Higher prevalence of initial drug resistance was observed among urban patients than rural patients and among young patients than old patients. These findings signify that a continuous survey on drug resistance permits to monitor efficiency of treatment programme of the country.

• Tuberculosis and Respiratory Diseases
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• v.57 no.6
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• pp.528-534
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• 2004

Background : Microscopic examination of sputum smears for acid-fast bacilli (AFB) is the most important and rapid diagnostic test for pulmonary tuberculosis. However, the AFB observed on the smear may represent either M. tuberculosis or nontuberculous mycobacteria (NTM). This study examined the clinical usefulness of a polymerase chain reaction test for M. tuberculosis (TB-PCR) for the differentiation of pulmonary tuberculosis and NTM lung disease in patients with smear-positive sputums in a tertiary hospital in Korea. Material and Methods : From January, 2003 to December, 2003, 826 AFB smear-positive and culture-positive sputum specimens were collected from 299 patients. Results : NTM were recovered from 26.6% (220/826) of the smear-positive sputum specimens and 23.4% (70/299) of the patients with smear-positive sputum. All the patients with isolated NTM had clinically significant NTM lung disease; 38 patients (54.3%) had M. avium and 26 patients (37.1%). had M. abscessus. In the patients with pulmonary tuberculosis, 78.7% of the patients (74/94) showed TB-PCR positivity, and all the patients with NTM lung disease showed negative results on the TB-PCR test (p<0.001). A positive result of the TB-PCR test on the sputum or bronchial washing fluid specimens was able to predict pulmonary tuberculosis with 88.4% sensitivity, 100% specificity, a 100% positive predictive value and a 79.7% negative predictive value for the patients with smear-positive sputum. Conclusion : The TB-PCR test for sputum specimens or bronchial washing fluid specimens could be useful for differentiating pulmonary tuberculosis and NTM lung disease for the patients with smear-positive sputum in Korea.

• Tuberculosis and Respiratory Diseases
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• v.56 no.3
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• pp.261-268
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• 2004

Background : The resurgence of tuberculosis and outbreaks of multidrug resistant (MDR) tuberculosis have increased the emphasis for the development of new susceptibility testing of the Mycobacterium tuberculosis for the effective treatment and control of the disease. Conventional drug susceptibility testings, such as those using egg-based or agar-based media have some limits, such as the time required and difficulties in determining critical inhibitory concentrations, but these are still being used in many diagnostic laboratories because of no better lternatives, considering cost and accuracy. To overcome these limits, a rapid and simple method for new susceptibility testing, using live and dead assays, was applied for a bacterial cell viability assay to distinguish dead from live bacterial cells based on two-color fluorescence. Materials and Methods Strains : Forty strains were used in this study, 20 susceptible to all antituberculosis drugs and the other 20 resistant to the four first line antituberculosis drugs isoniazid, rifampicin, streptomycin and ethambutol. Antibiotics : The four antibiotics were dissolved in 7H9 broth to make the following solutions: $0.1{\mu}g\;isoniazid(INH)/m{\ell}$, $0.4{\mu}g\;rifampicin(RMP)/m{\ell}$, $4.0{\mu}g\;streptomycin(SM)/m{\ell}$ and $4.0{\mu}g\;ethambutol(EMB)/m{\ell}$. Results : Live and dead Mycobacterium tuberculosis cells fluoresced green and red with the acridin (Syto 9) and propidium treatments, respectively. These results are very well accorded with conventional drug susceptibility testing by proportional method on Lowensen-Jensen media (L-J) containing 4 drugs (INH, RMP, EMB and SM), showing a 93.7 % accordance rate in susceptible strains and 95% in resistant strains. Conclusion : The results of the drug susceptibility testing using the live and dead bacterial cell assay showed high accordance rates compared with the conventional proportion method on L-J. This finding suggests that the live and dead bacterial cell assay can be used as an alternative to conventional drug susceptibility testing for M. tuberculosis strains.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.936-944
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• 1996

Background: Neutrophils or monocytes separated in vitro by the adherence to plastic surface are known to be activated by surface adherence itself and subsequent experimental data might be altered by surface adherence. Adhesion molecules and gene transcription of the inflammatory mediators are known to be associated in this process. To evaluate whether adhesion molecule and transcriptional activation of the inflammatory substances are also involved in the activation of human alveolar macrophage by the adherence procedure, we designed this experiment. Method : Bronchoalveolar lavage was performed in the person whose lung of either side was confirmed to be nonnal by chest cr and alveolar macrophage was harvested. To measure the expression of Interleukin-8(IL-8) mRNA, manganese superoxide dismutase(SOD) mRNA and CD11/CD18 mRNA in human alveolar macrophage of both adherence state and suspension state, Northern blot analysis was done at 0, 2, 4, 8 and 24hrs after the adherence to plastic surface and during suspension state. Then, phorbol myristate acetate(pMA) and N-formyl-methionyl-leucyl-phenylalanine(fMLP) were added respectively in the same experimental condition. Result : 1) Human alveolar macrophages in the adherent state induced IL-8 mRNA and SOD mRNA expression which was maximal at 8 hours after the adherence to plastic surface. But we could not observe the upregulation of CD18 mRNA by surface adherence. 2) PMA induced these mRNA expression both in the adherent cell and the nonadherem cells, but the induction of mRNA expression by fMLP occurred only in the adherent cells. Conclusion: These results suggest that adherence of huamn alveolar macropahge is an important cell-activating event that may play a critical role in the modulation of lung inflammatory respones.