• Tuberculosis and Respiratory Diseases
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• v.80 no.2
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• pp.159-168
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• 2017

Background: Streptomycin (SM) is recommended by the World Health Organization (WHO) as a part of standard regimens for retreating multidrug-resistant tuberculosis (MDR-TB) cases. The incidence of MDR-TB in retreatment cases was 19% in Thailand. To date, information on SM resistance (SMR) gene mutations correlated to the SMR of Mycobacterium tuberculosis Thai isolates is limited. In this study, the mutations in rpsL, rrs, gidB, and whiB7 were investigated and their association to SMR and the lineage of M. tuberculosis were explored. Methods: The lineages of 287 M. tuberculosis collected from 2007 to 2011 were identified by spoligotyping. Drug susceptibility profiles were evaluated by the absolute concentration method. Mutations in SMR genes of 46 SM-resistant and 55 SM-susceptible isolates were examined by DNA sequencing. Results: Three rpsL (Lys43Arg, Lys88Arg, and Lys88Thr) and two gidB (Trp45Ter and Gly69Asp) mutations were present exclusively in the SM resistant M. tuberculosis. Lys43Arg rpsL was the most predominant SMR mutations (69.6%) and prevailed among Beijing isolates (p<0.001). No SMR-related mutation in was found rrs. The combination of rpsL and gidB mutations provided 76.1% sensitivity for detecting SMR in M. tuberculosis Thai isolates. whiB7 was not responsible for SMR in SM resistant isolates lacking rpsL and rrs mutations. The significance of the three gidB mutations, 276A>C, 615A>G, and 330G>T, as lineage signatures for Beijing and EAI were underscored. This study identified 423G>A gidB as a novel sub-lineage marker for EAI6-BGD1. Conclusion: Our study suggested that the majority of SMR in M. tuberculosis Thai isolates were responsible by rpsL and gidB polymorphisms constantly providing the novel lineage specific makers.

• Tuberculosis and Respiratory Diseases
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• v.50 no.5
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• pp.599-606
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• 2001

Background : Since the advent of AIDS, tuberculosis has become a major public health problem in the western society. Therefore, it is essential that pulmonary tuberculosis be rapidly diagnosed. Light microscopic detection of acid-fast organisms in sputum has traditionally been used for rapidly diagnosing tuberculosis. However positive smears are only observed in about one-half to three-quarters of cases. Studies using PCR for diagnosing pulmonary tuberculosis disclosed several shortcomings suggesting an inability to distinguish between active and treated or inactive tuberculosis. In this study, the clinical significance of a PCR-based rapid technique for detecting Mycobacterium tuberculosis DNA in peripheral blood was investigated. Materials and Methods : From July 1, 1998 through to August 30, 1999, 59 patients with presumed tuberculosis, who had no previous history of anti-tuberculosis medication use within one year prior to this study were recruited and followed up for more than 3 months. AFB stain and culture in the sputum and/or pleural fluids and biopsies when needed were performed. Blood samples from each of the 59 patients were obtained in order to identify Mycobacterium Tuberculosis DNA by a PCR test. Results : 1) Forty five out of 59 patients had a final diagnosis of tuberculosis ; Twenty eight were confirmed as having active pulmonary tuberculosis by culture or biopsy. Four were clinically diagnosed with pulmonary tuberculosis. The other 13 patients were diagnosed as having tuberculous pleurisy (9) and extrapulmonary tuberculosis (4). 2) Fourteen patients showed a positive blood PCR test. The PCR assay correctly identified active tuberculosis in 13 out of 14 patients. The overall sensitivity and specificity of this blood peR assay for diagnosing tuberculosis were 29% and 93%, respectively. The positive predictive value was 93%, the negative predictive value was 29% and the diagnostic accuracy was 44%.3) Six out of 14(43%) patients with blood PCR positive tuberculosis were immunologically compromised hosts. 4) A simple chest radiograph in blood PCR positive tuberculosis patients showed variable and inconsistent findings. Conclusion : A peripheral blood PCR assay for Mycobacterium tuberculosis is not recommended as a screening method for diagnosing active tuberculosis. However, it was suggested that the blood PCR assay could contribute to an early diagnostic rate due to its high positive predictive value.

• Tuberculosis and Respiratory Diseases
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• v.41 no.5
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• pp.489-493
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• 1994

Background: Nicotinamide adenine dinucleotide glycohydrolase(NADase) is located on the surface of the cells. It is bound by glycosylphosphatidylinositol(GPI)-linkage, which can be cleaved by bacterial PI-specific phospholipase C(PI-PLC). Recently, it was studied that NADase was increased in infected tuberculosis animal, but absolute NADase is uncertainly increased because of high NADase in Mycobacterium tuberculosis. Therefore, we studied pure NADase activity in red blood cells of normal person and patients of tuberculosis. Method: We evaluated the 19 healthy adults and 16 tuberculosis infected patients, and then, the latter cases were evaluated after 3 months antituberculosis therapy. NADase activity was calculated by scintillated counting of cleaved radioactive [carbonyl-$^3H$] nicotinamide Result: NADase activity was $2021.1{\pm}824.0\;pmol/min/10^6$ erythrocytes in healthy adults vs. $3339.0{\pm}1568.0$ in tuberculosis infected patients, and was $3339.0{\pm}1568.0$ in pretreated patients vs. $2238.6{\pm}1013.1$ in same 3 months treated patients. Conclusion: NADase activity of erythrocytes is elevated in tuberculosis infection, and normalized afer antituberculosis therapy. Therefore, we suggested NADase activity as the new diagnostic and therapeutic indicator.

• Tuberculosis and Respiratory Diseases
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• v.43 no.2
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• pp.236-242
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• 1996

Intracranial tuberculoma results from hematogenous spread of pulmonary, intestinal or urogenital tuberculosis. However, it might be caused by pulmonary tuberculosis, mainly. Clinically, symptoms of intracranial tuberculoma are headache and seizure, its symptoms are simillar to intracranial tumor. A 25-year-old-unmarried shopgirl was visited to this hospital because of headache, dizziness and visual disturbance for couple weeks in Sep. 1995. She had been treated with anti-tuberculosis agents of miliary tuberculosis during past nine months period. Brain MRI revealed intracranial tuberculoma and brain edema but not involved optic nerve. Ophthalmic examination revealed severe papilledema and splinter hemorrhage with bitemporal hemianopsis and central scotoma. This finding was strongly suggested of optic disc tuberculoma. Her symptoms became much better following repeated retrobulbar steroid injection with continuous anti-tuberculosis agents. We report a interesting case with intracranial tuberculoma and optic disc tuberculoma associated by miliary tuberculosis during anti-tuberculous treatment.

• Tuberculosis and Respiratory Diseases
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• v.46 no.4
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• pp.473-480
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• 1999

Background: Early diagnosis of tuberculosis is critical, especially in Korea, an area where tuberculosis is endemic. Because antibody responses to some membrane proteins of Mycobacterium tuberculosis are not comparable, and the policy of BCG vaccination and the prevalence of tuberculosis are different from country to country, the usefulness of the serological diagnostic tests is questionable in Korea, even though they have been confirmed to be useful in other countries. In the specific context of Korea, we tried to evaluate the validity of the ICT Tuberculosis Test (ICT), a membrane-based antibody kit that purports to detect the 5 M. tuberculosis complex-specific antigens including 38-kDa protein. Method: 68 patients with tuberculosis were tested : 37 had no history of previous tuberculosis, and 31 were reactivated cases. The control group comprised 77 subjects : 25 healthy adults, 35 hospital workers with frequent contact with tuberculosis patients, and 17 in-patients with non-tuberculous respiratory diseases. Results: The diagnostic sensitivities of the ICT were 87% and 73% in patients with versus without previous history of tuberculosis, respectively. The sensitivities of smear-positive and smear-negative patient groups were 81% and 73%, respectively. Both of the two patients with extrapulmonary tuberculosis tested positive through the ICT. The specificities of the ICT were 88%, 94%, and 94% in healthy adults, hospital workers, and non-tuberculous patients, respectively, with an overall specificity of 92%. Conclusion: It is suggested that when combined with traditional techniques, the ICT is an useful tool for the diagnosis of pulmonary tuberculosis. The procedure is simple, easy to perform, rapid, and needs no equipment. It shows 73% sensitivity and 92% specificity for the diagnosis of tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.41 no.3
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• pp.239-247
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• 1994

Background: T cell mediated immunity is important in the defense mechanism of tuberculosis. Since ${\gamma}{\delta}$ T cell receptor was found to react with 65 kD heat shock protein of M.tuberculosis, there have been some reports on the role of ${\gamma}{\delta}$ T cells in the defense against M.tuberculosis. But until now, the role of the ${\gamma}{\delta}$ T cells in tuberculosis is not clear. Methods: We therefore measured the percentage of ${\gamma}{\delta}$ T cells of peripheral blood by flowcytometry before and after stimulation with Con-A, PPD and H37Ra lysate and compared between tuberculosis patients and healthy controls. Results: ${\gamma}{\delta}$ T cells of pheripheral blood in pulmonary tuberculosis patients was $7.5{\pm}5.2%$, showing no difference compared with healthy control($10.0{\pm}4.8%$). But IL-2R(+) ${\gamma}{\delta}$ T cells were higher in tuberculosis compared with healthy control($4.8{\pm}5.1%$ vs. $1.8{\pm}2.8%$). After stimulation with PPD or Con-A, the percentage of ${\gamma}{\delta}$ T cells showed no significant change, but IL-2R(+) ${\gamma}{\delta}$ T cells increased significantly in both tuberculosis($17.9{\pm}13.4%,\;57.6{\pm}20.2%$ respectively) and healthy control group($11.5{\pm}9.1%,\;80.8{\pm}9.3%$). After stimulation with H37Ra lysate, percentage of ${\gamma}{\delta}$ T cells showed increasing tendency in healthy control group, but it was not statistically significant. Conclusion: In this study, we could not demonstrate the role of ${\gamma}{\delta}$ T cells in the peripheral blood of pulmonary tuberculosis. It is suggested that further studies will be needed in the regional sites of M.tuberculosis infection.

• Tuberculosis and Respiratory Diseases
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• v.65 no.6
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• pp.522-526
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• 2008

A 63-year old woman was admitted to our hospital for an evaluation of thrombocytopenia. She had been diagnosed with tuberculous pericarditis three months earlier in a local clinic and treated with anti-tuberculosis medication. Two months later, thrombocytopenia developed. The medication was subsequently stopped because it was suspected that the anti-tuberculosis medication, particularly rifampin, might have caused the severe platelet reduction. However, the thrombocytopenia was more aggravated. A bone marrow biopsy was performed, which showed moderate amounts of histiocytes with active hemophagocytosis. This finding strongly suggested that the critical thrombocytopenia had been caused by hemophagocytic syndrome, not by the side effects of the anti-tuberculosis medication. Furthermore, the development of hemophagocytosis might have been due to an uncontrolled tuberculosis infection and its associated aberrant immunity. Therefore, she was started with both standard anti-tuberculosis medication and chemotherapy using etoposide plus steroid. One month after the initiation of treatment, the thrombocytopenia had gradually improved and she was discharged in a tolerable condition. At the third month of the follow-up, her platelet level and ferritin, the activity marker of hemophagocytic syndrome, was within the normal range.

• Tuberculosis and Respiratory Diseases
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• v.41 no.2
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• pp.73-86
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• 1994

In addition to classic cholinergic and adrenergic pathways, the existence of a third division of autonomic control in the human airways has been proved. It is called a nonadrenergic noncholinergic(NANC) nervous system, and difficult to study in the absence of specific blockers. Neuropeptides are certainly suggested to be transmitters of this NANC nervous system. It is very frustrating to understand the pathophysiologic role of these peptides in the absence of any specific antagonists. However, further studies of neuropeptides might eventually lead to novel forms of treatment for bronchial asthma. Another study of the interaction between different components of the autonomic nervous system, either in ganglionic neurotransmission or by presynaptic modulation of neurotransmitters at the end-organ will elute neural control in airway disease, particularly in asthma. Studies of how autonomic control may be disordered in airway disease should lead to improvements in clinical management. Epithelial damage due to airway inflammation in asthma may induce bronchial hyperresponsiveness. Axon reflex mechanism is one of possible mechanisms in bronchial hyperresponsiveness. Epithelial damage may expose sensory nerve terminals and C-fiber nrve endings are stimulated by inflammatory mediators. Bi-directional communication between the nerves and mast cells may have important roles in allergic process. The psychological factors and conditioning of allergic reactions is suggested that mast cell activation might be partly regulated by the central nervous system via the peripheral nerves. Studies in animal models, in huamn airways in vitro and in patients with airway disease will uncover the interaction between allergic disease processes and psychologic factors or neural mechainsms.

• Tuberculosis and Respiratory Diseases
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• v.48 no.5
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• pp.699-708
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• 2000

Background : A presumptive histopathologic diagnosis of tuberculosis is commonly based on the finding of acid-fast bacilli upon microscopic examination of a diagnostic specimens. Although this traditional histochemical staining method is satisfactory, it is time-consuming and not species-specific. For more specific assessment, in situ hybridization assay with oligonucleotide probes is introduced. Methods : The human surgical specimens were obtained from tuberculosis patients, and experimental specimens were made by injecting cultured M. tuberculosis organisms into fresh rat liver. Oligonucleotide probes complementary to ribosomal RNA portion were synthesized and labeled with multiple biotin molecules. For a rapid detection, all procedures were carried out using manual capillary action technology on the Microprobe staining system. Results : The in situ hybridization assay produced a positive reaction in experimental specimens (80-90% sensitivity) after pepsin-HCl pre-treatment for a good permeabilization of probes, but reliable result was not obtained from human surgical specimens. Conclusion : It is, therefore, suggested that biotin-labeled oligonucleotide probes have considerable potential for identification and in situ detection of M. tuberculosis but, there are some barriers to overcome for the diagnostic use of this method.

• Journal of Yeungnam Medical Science
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• v.37 no.4
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• pp.277-285
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• 2020

Tuberculosis (TB) is still a major health problem worldwide. Especially, multidrug-resistant TB (MDR-TB), which is defined as TB that shows resistance to both isoniazid and rifampicin, is a barrier in the treatment of TB. Globally, approximately 3.4% of new TB patients and 20% of the patients with a history of previous treatment for TB were diagnosed with MDR-TB. The treatment of MDR-TB requires medications for a long duration (up to 20-24 months) with less effective and toxic second-line drugs and has unfavorable outcomes. However, treatment outcomes are expected to improve due to the introduction of a new agent (bedaquiline), repurposed drugs (linezolid, clofazimine, and cycloserine), and technological advancement in rapid drug sensitivity testing. The World Health Organization (WHO) released a rapid communication in 2018, followed by consolidated guidelines for the treatment of MDR-TB in 2019 based on clinical trials and an individual patient data meta-analysis. In these guidelines, the WHO suggested reclassification of second-line anti-TB drugs and recommended oral treatment regimens that included the new and repurposed agents. The aims of this article are to review the treatment strategies of MDR-TB based on the 2019 WHO guidelines regarding the management of MDR-TB and the diagnostic techniques for detecting resistance, including phenotypic and molecular drug sensitivity tests.