• Tuberculosis and Respiratory Diseases
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• v.70 no.3
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• pp.251-256
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• 2011

The prevalence of multi-drug resistant tuberculosis (MDR-TB), which is resistant to isoniazid and rifampin, has been increasing in Korea. And the side effects of 2nd line anti-tuberculosis medications, including drug-induced hepatitis, are well known. Although prothionamide (PTH) is one of the most useful anti-TB medications and although TB medication-induced acute hepatitis is a severe complication, there are only a few published case reports about prothionamide induced hepatitis. In this case report, a 22 year old male was diagnosed with pulmonary MDR-TB and was administered 2nd line anti-TB mediations, including PTH. Afterwards, he had a spiking fever and his liver enzymes were more than 5 times greater than the upper limit of the normal range. He was then diagnosed with drug-induced hepatitis by liver biopsy. His symptoms and liver enzyme elevation were improved after stopping PTH. Accordingly, we report this case of an association between PTH and acute hepatitis.

• Journal of the Korean Chemical Society
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• v.66 no.3
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• pp.194-201
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• 2022

A simple, efficient, and cost-effective method has been employed for the synthesis of 2,4,5-trisubstituted imidazole derivatives (3a-j) containing quinoline substituent at 2^nd position. Title compounds were obtained by multicomponent reaction (MCR), involving aryl substituted 1,2-diketone, quinoline carbaldehyde and ammonium acetate in the presence of acetic acid solvent under mild reaction conditions. The newly synthesized quinoline containing imidazole derivatives were confirmed through FT-IR, ¹H-NMR, ¹³C-NMR and mass spectral analysis. In-vitro microplate alamar blue assay (MABA) to determine the MIC (minimum inhibitory concentration) values against Mycobacterium tuberculosis H37Rv was performed for the synthesized compounds. The synthesized compounds exhibited activity against Mycobacterium tuberculosis and among which compounds, 3d, 3f and 3i showed good activity. The highest activity was showed with compound 3i. The anti-mycobacterial activity results are well correlated with the computational molecular docking analysis, which was performed for the synthesized compounds prior to the evaluation of the activity.

• Genomics & Informatics
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• v.21 no.3
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• pp.42.1-42.23
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• 2023

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, one of the most deadly infections in humans. The emergence of multidrug-resistant and extensively drug-resistant Mtb strains presents a global challenge. Mtb has shown resistance to many frontline antibiotics, including rifampicin, kanamycin, isoniazid, and capreomycin. The only licensed vaccine, Bacille Calmette-Guerin, does not efficiently protect against adult pulmonary tuberculosis. Therefore, it is urgently necessary to develop new vaccines to prevent infections caused by these strains. We used a subtractive proteomics approach on 23 virulent Mtb strains and identified a conserved membrane protein (MmpL4, NP_214964.1) as both a potential drug target and vaccine candidate. MmpL4 is a non-homologous essential protein in the host and is involved in the pathogen-specific pathway. Furthermore, MmpL4 shows no homology with anti-targets and has limited homology to human gut microflora, potentially reducing the likelihood of adverse effects and cross-reactivity if therapeutics specific to this protein are developed. Subsequently, we constructed a highly soluble, safe, antigenic, and stable multi-subunit vaccine from the MmpL4 protein using immunoinformatics. Molecular dynamics simulations revealed the stability of the vaccine-bound Tolllike receptor-4 complex on a nanosecond scale, and immune simulations indicated strong primary and secondary immune responses in the host. Therefore, our study identifies a new target that could expedite the design of effective therapeutics, and the designed vaccine should be validated. Future directions include an extensive molecular interaction analysis, in silico cloning, wet-lab experiments, and evaluation and comparison of the designed candidate as both a DNA vaccine and protein vaccine.

• Clinical and Experimental Pediatrics
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• v.52 no.1
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• pp.61-67
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• 2009

Purpose : The rate of drug-resistant tuberculosis (DR-TB) in children is an indicator of the effectiveness of TB control programs in the community. This study aimed to assess the prevalence of DR-TB in children and evaluate TB management. Methods : Between January 1999 and July 2007, drug susceptibility tests for anti-TB drugs were employed for patients aged less than 19 years with culture-positive TB. Results : A total of 607 cases (16.6%) were resistant to at least one anti-TB drug as follows: isoniazid (INH; 13.8%), rifampin (8.9%), pyrazinamide (4.2%), streptomycin (3.7%), ethambutol (EMB; 5.9%), and para-aminosalicylic acid (PAS; 1.9%). Multidrug-resistant (MDR) TB was found in 276 cases (7.6%); extensive drug resistant (XDR) TB, in 5 cases (0.2%). The rate of resistance to at least one anti-TB drug in children aged >15 years (16.1%) was significantly lower than that in children aged <15 years (20.5%) (P=0.016). The rate of resistance to at least one anti-TB drug and multidrug-resistance in this survey decreased significantly (P<0.001) as compared to the previous survey (1987-1995). The rate of resistance to INH, EMB, and PAS also significantly decreased (P<0.05). Conclusion : The rate of DR-TB in children in Korea has decreased over time; however, it remains higher than that in other countries. MDR-TB and XDR-TB are the emerging problems in Korean children. Therefore, the selection of effective drugs through drug susceptibility tests and evaluating risk factors of resistant TB is essential to successful therapy and a decreased incidence of DR-TB.

• Annals of Laboratory Medicine
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• v.38 no.6
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• pp.569-577
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• 2018

Background: The increasing prevalence of drug-resistant tuberculosis (TB) infection represents a global public health emergency. We evaluated the usefulness of a newly developed multiplexed, bead-based bioassay (Quantamatrix Multiplexed Assay Platform [QMAP], QuantaMatrix, Seoul, Korea) to rapidly identify the Mycobacterium tuberculosis complex (MTBC) and detect rifampicin (RIF) and isoniazid (INH) resistance-associated mutations. Methods: A total of 200 clinical isolates from respiratory samples were used. Phenotypic anti-TB drug susceptibility testing (DST) results were compared with those of the QMAP system, reverse blot hybridization (REBA) MTB-MDR assay, and gene sequencing analysis. Results: Compared with the phenotypic DST results, the sensitivity and specificity of the QMAP system were 96.4% (106/110; 95% confidence interval [CI] 0.9072-0.9888) and 80.0% (72/90; 95% CI 0.7052-0.8705), respectively, for RIF resistance and 75.0% (108/144; 95% CI 0.6731-0.8139) and 96.4% (54/56; 95% CI 0.8718-0.9972), respectively, for INH resistance. The agreement rates between the QMAP system and REBA MTB-MDR assay for RIF and INH resistance detection were 97.6% (121/124; 95% CI 0.9282-0.9949) and 99.1% (109/110; 95% CI 0.9453-1.0000), respectively. Comparison between the QMAP system and gene sequencing analysis showed an overall agreement of 100% for RIF resistance (110/110; 95% CI 0.9711-1.0000) and INH resistance (124/124; 95% CI 0.9743-1.0000). Conclusions: The QMAP system may serve as a useful screening method for identifying and accurately discriminating MTBC from non-tuberculous mycobacteria, as well as determining RIF- and INH-resistant MTB strains.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.7 no.1
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• pp.102-107
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• 2004

About 20% of intestinal tuberculosis have active pulmonary tuberculosis. Intestinal tuberculosis can develop by swallowing sputum which have active pulmonary tuberculosis and by ingestion of contagious milk. We report a case of intestinal tuberculosis complicated with pulmonary tuberculosis in a 15-year old aldelescent who could not cough out sputum because of known cerebral palsy. He was admitted because of 3 day history of fever and bloody stool. Chest PA showed both upper lobe consolidation. AFB stain and AFB PCR was positive for tuberculosis. Colon study showed abscence of haustral marking and lead pipe appearance due to stenosis of ascending colon and mucosal edema. Abdominal CT scan showed mild wall thickening in ascending colon. Despite the anti-tuberculosis therapy with first line drugs, fever accompanying pleural effusion developed. Second line drug with Isoniazid and Rifampin improved clinical manifestation. After the report on sensitivity, we readjusted the regimen, and clinical manifestations improved gradually.

• Tuberculosis and Respiratory Diseases
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• v.59 no.3
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• pp.266-271
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• 2005

Background : Ethambutol(EMB) is one of the first-line drugs included in short-course anti-tuberculosis therapy. The point mutations in embB gene have been speculated to be associated EMB resistance. However, detection of embB mutations at these positions have been observed in both EMB-susceptible isolates; thus, it remains controversial whether these mutations are associated with EMB resistance Methods : The 36 M. tuberculosis isolates were selected from clinical isolates which tested susceptible to EMB and resistant to at least one drug. DNA extracted from the isolates was analyzed by amplifying embB gene. The PCR products were purified and directly sequenced. We reviewed the history of past drug susceptibility test results. Results : Out of 36 EMB-susceptible strains, 3 strains (8.3%) had a mutation in codon 306 or 406 of the embB gene. These three strains had at least isoniazid resistance. They grew at 1.0 mcg/ml of EMB in Lowenstein-Jensen media. The patients of the strains were continuously smear-positive for over 3 years despite taking TB therapy. One strain had been EMB-resistant in past drug susceptibility tests. Conclusion : EMB-susceptible strains containing embB mutation may be caused by decreased viability in vitro test not by itself.

• Tuberculosis and Respiratory Diseases
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• v.38 no.2
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• pp.93-98
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• 1991

A clinical trial was made on 76 patients with pulmonary tuberculosis to determine the effectiveness and acceptibility of 6 month 2SHRZ/4HR antituberculosis regimen. Out of 76 patients, 13 patients (17.1%) dropped out and 11 patients (14.5%) were excluded due to drug resistance. In 3 patients (3.9%), regimen was changed due to adverse effects. Treatment failure rate was 2.0% in 50 patients. One patient, who had far advanced lesion, was treated longer than 6 months due to failure of sputum conversion. The most common adverse effect was arthralgia, which was controlled by the administration of allopurinol and nonsteroidal anti-inflammatory drug. In conclusion, 2SHRZ/4HR for 6 months was effective regimen in treating the newly-diagnosed patients with tuberculosis, but change of the regimen and duration might be carefully considered by the severity of the lesion and adverse effect of the drug But further study will be needed to evaluate not only the efficacy and efficiency of 6 month chemotherapy but also relapse rates.

• Tuberculosis and Respiratory Diseases
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• v.80 no.2
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• pp.136-142
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• 2017

Assessing response to therapy allows for prospective end point evaluation in clinical trials and serves as a guide to clinicians for making decisions. Recent prospective and randomized trials suggest the development of imaging techniques and introduction of new anti-cancer drugs. However, the revision of methods, or proposal of new methods to evaluate chemotherapeutic response, is not enough. This paper discusses the characteristics of the Response Evaluation Criteria In Solid Tumor (RECIST) version 1.1 suggested in 2009 and used widely by experts. It also contains information about possible dilemmas arising from the application of response assessment by the latest version of the response evaluation method, or recently introduced chemotherapeutic agents. Further data reveals the problems and limitations caused by applying the existing RECIST criteria to anti-cancer immune therapy, and the application of a new technique, immune related response criteria, for the response assessment of immune therapy. Lastly, the paper includes a newly developing response evaluation method and suggests its developmental direction.

• Pediatric Infection and Vaccine
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• v.18 no.1
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• pp.1-14
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• 2011

Tuberculosis is a disease with high morbidity and mortality in children worldwide. Despite the decrease in the incidence of tuberculosis in Korea, more than 30,000 new patients are diagnosed each year. Active tuberculosis is less frequent in children compared to adults but the risk of miliary tuberculosis and CNS tuberculosis is much higher. The diagnosis of tuberculosis in children and adolescents is difficult due to the nonspecific symptoms upon presentation. Diagnostic work up is based on the confirmation of tuberculosis infection by tuberculin skin test, abnormal radiologic findings, and contact with an adult with active tuberculosis. Anti-tuberculosis medications are prescribed according to the drug susceptibility of the index patient. Latent tuberculosis infection plays an important role in adult tuberculosis by reactivation. Thus, it is critical to accurately diagnose latent tuberculosis in children to prevent reactivation in adulthood. Korean guidelines for diagnosis and treatment of tuberculosis in children and adolescents provide evidence based recommendations in the optimal diagnosis and treatment for active and latent tuberculosis in children and adolescents based on the current Korean situation.