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In this study, new benzothiazole–pyrimidine hybrids (5a–c, 6, 7a–f, and 8–15) were designed and synthesised. Two different functionalities on the pyrimidine moiety of lead compound 4 were subjected to a variety of chemical changes with the goal of creating various functionalities and cyclisation to further elucidate the target structures. The potency of the new molecules was tested against different tuberculosis (TB) strains. The results indicated that compounds 5c, 5b, 12, and 15 (MIC = 0.24–0.98 µg/mL) are highly active against the first-line drug-sensitive strain of Mycobacterium tuberculosis (ATCC 25177). Thereafter, the anti-tubercular activity was evaluated against the two drug-resistant TB strains; ATCC 35822 and RCMB 2674, where, many compounds exhibited good activity with MIC = 0.98–62.5 3 µg/mL and 3.9–62.5 µg/mL, respectively. Compounds 5c and 15 having the highest anti-tubercular efficiency towards sensitive strain, displayed the best activity for the resistant strains by showing the MIC = 0.98 and 1.95 µg/mL for MDR TB, and showing the MIC = 3.9 and 7.81 µg/mL for XDR TB, consecutively. Finally, molecular docking studies were performed for the two most active compounds 5c and 15 to explore their enzymatic inhibitory activities. [ABSTRACT FROM AUTHOR]

Perinatal tuberculosis is a rare disease with high mortality and a challenging diagnosis. We reported a 56-day-old female infant with cough and wheezing. Her mother had miliary tuberculosis. Gastric aspirate smear, tuberculin skin test, blood and sputum culture of the infant were negative. Thoracic computed tomography demonstrated several consolidated patches with diffuse high-density nodular opacities in bilateral lungs. Fiberoptic bronchoscopy was performed to obtain bronchoalveolar lavage fluid, reduce secretion and restore airway patency on 2 days after admission. Mycobacterium tuberculosis was detected by bronchoalveolar lavage fluid Xpert MTB/RIF and rifampicin resistance was negative on 3 days after admission. Appropriate anti-tuberculosis drug was chosen. The infant made a good recovery. Fiberoptic bronchoscopy plays a vital role in diagnosing rapidly and treating perinatal tuberculosis. And it could be promoted as an important approach to the management of perinatal tuberculosis. [ABSTRACT FROM AUTHOR]

An innovative class of novel 2-aryl-5-(1-aryl-1H-pyrazol-3-yl)-1,3,4-oxadiazoles 5i–w have been synthesized from ring transformation using L-proline as an organocatalyst. This novel method using organocatalyst is a splendid example of the green reaction with improved yields. The molecular docking analysis of compounds 5i–w were investigated with enoyl-acyl carrier protein reductase (InhA) enzyme (PDB ID: 4TZK) as anti-tubercular target molecules. The docking study implied that the synthesized compounds exhibited favorable binding modes and affinity. Further, the anti-tubercular activity was investigated against Mycobacterium tuberculosis (MTB) H37Rv strain which demonstrated that the compounds 5i, 5j, 5k, and 5l exhibited excellent activity at the 6.25 µg/ml concentrations, whereas the compounds 5m, 5n, 5o, 5s, and 5w have shown the activity at 12.50 µg/ml concentration, respectively. [ABSTRACT FROM AUTHOR]

Joining the global fight against Tuberculosis, the world's most deadly infectious disease, herein we present the design and synthesis of novel isatin-nicotinohydrazide hybrids (5a–m and 9a–c) as promising anti-tubercular and antibacterial agents. The anti-tubercular activity of the target hybrids was evaluated against drug-susceptible M. tuberculosis strain (ATCC 27294) where hybrids 5d, 5g and 5h were found to be as potent as INH with MIC = 0.24 µg/mL, also the activity was evaluated against Isoniazid/Streptomycin resistant M. tuberculosis (ATCC 35823) where compounds 5g and 5h showed excellent activity (MIC = 3.9 µg/mL). Moreover, the target hybrids were examined against six bronchitis causing-bacteria. Most derivatives exhibited excellent antibacterial activity. K. pneumonia emerged as the most sensitive strain with MIC range: 0.49–7.81 µg/mL. Furthermore, a molecular docking study has proposed DprE1 as a probable enzymatic target for herein reported isatin-nicotinohydrazide hybrids, and explored the binding interactions within the vicinity of DprE1 active site. [ABSTRACT FROM AUTHOR]

Objective: A prospective clinical study to assess the utility of CD4 + T cell lymphocyte profiling from peripheral blood in patients with ocular tuberculosis (TB).Methods: Thirty-six Asian patients with presumed diagnosis of ocular TB were recruited for T-lymphocyte profiling. MTB antigen specific CD4 assay was set up, and flow cytometric data were analyzed using FlowJo software.Results: There was no significant difference between treatment responders and non-responders for the proportion of CD4 + T cells specific for PPD or ESAT-6+ CFP-10, but treatment responders did have significantly higher frequency of CD38+ (p = .0357) and CD38+ HLA-DR+ (p = .0357) on the PPD-specific CD4 + T cells.Conclusion: This study is one of the first of its kind to look into MTB specific T cell activation marker profiling of peripheral blood in patients with ocular TB. Further studies need to be undertaken to assess the utility of CD4 + T cell phenotypes as a biomarker for ocular TB. [ABSTRACT FROM AUTHOR]

Tuberculous meningitis (TBM) is now uncommon in high-income countries. It is the most severe form of extrapulmonary tuberculosis with high rates of mortality and morbidity if diagnosis and treatment are delayed. An 8-month-old girl with TBM who was treated with high-dose intravenous anti-tuberculous drugs (ATD) is reported. Therapeutic drug monitoring (TDM) of isoniazid and rifampicin was undertaken by measuring serial drug concentrations in serum and cerebrospinal fluid (CSF). There was rapid eradication of Mycobacterium tuberculosis from the CSF with a good clinical outcome and no adverse effects. Using high-dose regimens of intravenous ATD to treat TBM is an important option in order to obtain sufficient CSF diffusion. When available, TDM and a multidisciplinary approach are essential for efficient therapeutic management. [ABSTRACT FROM AUTHOR]

The present study was conducted to formulate and investigate liposomes for the dual drug delivery based on anti-tubercular drug(s) combination i.e. Isoniazid (INH) and Rifampicin (RIF). Mannosylated and non mannosylated liposomes were prepared by lipid thin film hydration method, using DSPC: Chol at a molar ratio 6:4 while in case of mannosylated liposomes DSPC: Chol: Man-C4-Chol at a molar ratio 6.0:3.5:0.5 were used and extensively characterised. The particle size and zeta potential were recorded to be 1.29 ± 0.24 µm and −9.1 ± 0.11 mV. The drug entrapment (%) was recorded to be 84.7 ± 1.25% for Rifampicin and 31.8 ± 0.12% for Isoniazid. The antitubercular activity studied in Balb/C mice was maximum in the case of mannosylated liposomes. The biodistribution studies also revealed higher drug(s) concentration (accumulation) maintained over a protracted period. The liposomal preparations are passively as well as actively uptaken by the alveolar macrophages which are the cellular tropics of infection. The mannosylated liposomes appear to be a potential carrier for dual drug delivery and targeted antitubercular therapy. [ABSTRACT FROM AUTHOR]

Acetyl Coenzyme A Carboxylase (AccD6) is a homodimeric protein which is involved in the carboxylation of acetyl coenzyme A to produce malonyl coenzyme A, which plays an important role in the biosynthesis of fatty acid chain. However, studies suggest that AccD6 in combination with AccA3 produces malonyl co-A. Certain herbicides are known to inhibit plant ACC. Among these herbicides, haloxyfop was found to inhibit AccD6 at IC50 of 21.1 ± 1 µM. In this study, we have performed molecular docking of the Maybridge database consisting of ~55,000 compounds in the active site of the protein with haloxyfop as a reference molecule, followed by molecular dynamics study and biological activity determination of prioritized compounds. Out of the nine compounds selected for biological evaluation, three compounds – CD07230, HTS08529 and KM08871 – were found to exhibit anti-mycobacterial activity. [ABSTRACT FROM AUTHOR]

Smoking is a cause behind many diseases, including tuberculosis, and it is a risk factor for tuberculosis infection and mortality. Moreover, smoking is associated with a poor tuberculosis treatment outcome. In this study, we focus on the effects of cigarette smoke on an infected cell culture treated with anti-tuberculosis drugs. Cytotoxicity on THP-1, J774A.1 and MH-S cell lines and growth of Mycobacterium tuberculosis exposed to a reference or a commercial cigarette was evaluated. THP-1 cell line was exposed to cigarette smoke, infected with Mycobacterium tuberculosis and treated with anti-tuberculosis drugs. Apoptosis and death cell were also tested on M. bovis BCG infected cells. Minimal inhibitory concentrations of anti-tuberculosis drugs were analyzed. All cells lines showed viability values higher than 80% when exposed to cigarette smoke extract. However, THP-1 cell line infected with M. bovis BCG and exposed to Marlboro cigarette smoke showed up to a 54% reduction of apoptotic cells than cells unexposed to smoke. M. tuberculosis exposed to Marlboro cigarette smoke for 11 days had an optical density 16% lower than unexposed bacteria. When cells were infected with M. tuberculosis, the intracellular recovery of CFUs showed up to a 0.66 log reduction in cells exposed to cigarette smoke extract because of a potential impairment in the phagocytosis. Macrophages treated with drugs showed up to a 2.55 log reduction in the intracellular load burden compared with non-treated ones. Despite poor treatment outcome on TB smoker patients, minimal inhibitory concentration of rifampicin increased only 2-fold in M. tuberculosis exposed to cigarette smoke. Smoking interferes with tuberculosis treatment impairing the immunity of the host. [ABSTRACT FROM AUTHOR]

In search of more potent new antitubercular agents, a library of novel piperazine tethered dimeric 1,2,3-triazoles were designed by assembling 1,2,3-triazoles and piperazine in a single molecular architectural framework. The titled compounds (3a–m) were synthesized by 1,3-dipolar cycloaddition of 1,4-di(prop-2-yn-1-yl)piperazine (1) and various azides (2a–m) using click chemistry approach with good yields. All the synthesized compounds (3a–m) have been screened for their in vitro antitubercular, antifungal and antioxidant activities against their respective strains. Among them, 3b, 3d, and 3i have revealed promising antitubercular activity against Mycobacterium tuberculosis (Mtb) H37Rv with MIC 12.5 µg/mL. Molecular docking results provided well-clustered solutions to the mode of binding for these molecules into the active site of Mtb enoyl reductase (InhA). In addition to this, most of synthesized compounds were found to have potential antifungal as well as antioxidant activity. [ABSTRACT FROM AUTHOR]

Healing clay is a rich source of diverse minerals. The relevance of these indigenous minerals in the improvement of antibiotic chemotherapy against prevailing bacterial pathogens is yet to be thoroughly explored. In the present study, healing clay from archaeological context was characterized and used in combination with 19 different antibacterial drugs to test their combined in vitro activity against Mycobacterium smegmatis mc2 155 and a multidrug-resistant (MDR) Mycobacterium smegmatis strain. Among the antibiotics tested, the anti-tuberculosis drug, pyrazinamide (Pzd), showed a drastic antimycobacterial activity against Mycobacterium smegmatis mc2 155 in the presence of 5 µg/µL of the healing clay, whereas ribosome targeted inhibitors such as gentamicin showed significant reduction in activity in the presence of the healing clay. The resistance phenotype of the MDR Mycobacterium smegmatis strain to ampicillin and isoniazid was reversed in the presence of the healing clay. The activity of the other antibiotics was either unaffected, enhanced or reduced in the presence of the healing clay. The activity of ampicillin and isoniazid against the MDR strain in the presence of the healing clay suggest that healing clay might be a useful synergy for these antibiotics against MDR Mycobacterium tuberculosis. [ABSTRACT FROM AUTHOR]

In a search for safer and potent antitubercular agents, here a library of newly substituted dioxoisoindolinylmethyl-triazolyl-N-phenylacetamide derivatives (5a–l) has been synthesized via click chemistry approach. All synthesized compounds were evaluated for their antitubercular activity against Mycobacterium tuberculosis H37Rv (MTB). Among the screened compounds, 5d, 5e, 5h, and 5l showed good antitubercular activity. The compounds 5d and 5l have shown very effective antitubercular activity against Mycobacterium tuberculosis H37Rv (MTB) with MIC 12.5 μg/mL. All the newly synthesized compounds were thoroughly characterized by 1H NMR, 13C NMR, and HRMS spectral data. We further performed exploratory docking studies on the crystal structure of Mycobacterium tuberculosis enoyl reductase to demonstrate the mechanism of antitubercular activity. [ABSTRACT FROM AUTHOR]

Context: The roots of Lophira lanceolata Van Tiegh. Ex Keay (Ochnaceae) have numerous medicinal values in the Central African region. Even though the MeOH extract of the roots has shown antimycobacterial activities, the constituents responsible for this inhibitory activity remain unknown. Objective: Phytochemical investigation of the MeOH root extract of L. lanceolata and determination of the antimycobacterial activities of that extract and constituents against the growth of Mycobacterium tuberculosis. Materials and methods: Column chromatography was used to provide bioactive phytoconstituents. Those compounds were elucidated using MS and NMR spectroscopic data. Antimycobacterial screening of the extract (4.882-5000 µg/mL in DMSO during 24 h at 37 °C) and isolated compounds (0.244-250 µg/mL in DMSO during 24 h at 37 °C) was performed by microplate alamar blue assay (MABA) against two mycobacterial strains. Results: The investigation of L. lanceolata MeOH roots extract provided of mixture of unseparated biflavonoids with a newly described one, dihydrolophirone A (1a) associated to lophirone A (1b). The bioactive compounds that effectively inhibited the growth of M. tuberculosis AC45 were found to be compounds 1 and 2. They exhibited MIC values of 31.25 and 15.75 µg/mL, respectively, and their MIC was found to be 62.5 µg/mL against resistant strain AC83. Discussion and conclusions: It is clearly evident from the results obtained that the mycobacterial activity of L. lanceolata could be related mainly to its steroid and flavonoid contents. Therefore, this study suggests the potential of the above-mentioned classes of compounds as promising candidate agents for developing new anti-tuberculosis drugs. [ABSTRACT FROM AUTHOR]

The present study describes L-hydroxy proline catalyzed unpredicted formation of 4,5-dihydro-1H-pyrazolo[3,4-b]pyridines instead of expected 4,7-dihydro-1H-pyrazolo[3,4-b]pyridines in aqueous ethanol at ambient temperature through one-pot three-component reaction. Furthermore, this protocol was evaluated using green chemistry metrics indicating green relevance of the present synthetic methodology. Most of the synthesized compounds were evaluated for their antitubercular activity against Mycobacterium tuberculosis H37RV strain, showing excellent results based on minimum inhibitory concentrations (MIC). Among the screened derivatives 4f, 4i, and 4j exhibited antitubercular activity with promising MIC value of 1.6 μg/mL. [ABSTRACT FROM AUTHOR]

Purpose: Correlation of results of polymerase chain reaction for Mycobacterium tuberculosis (MTB PCR) with clinical features and treatment response in tubercular uveitis.Methods: Retrospective case study.Results: Among 56 patients, 31 (55.3%) had acute and 25 (44.6%) had chronic uveitis. Uveitis was unilateral in 40 (71.4%) and bilateral in the remaining 16 (28.6%). Anatomical subtypes of uveitis were: anterior in 10 (13.9%) eyes, intermediate in 9 (12.5%), posterior in 17 (23.6%), and pan uveitis in 36 (50%) eyes. MTB PCR was positive in 24 patients. There was an 80% correlation between clinical response to antitubercular therapy (ATT) and PCR results. Twenty-two patients with positive PCR had a good clinical response. The sensitivity and specificity was 73.3% and 92.3%, respectively.Conclusions: The diagnosis of intraocular TB requires strong clinical suspicion with corroborative laboratory and radiological evidence. A positive PCR is reliable whereas negative results should be correlated with clinical features. An adequate response to ATT supports PCR results. [ABSTRACT FROM AUTHOR]

Purpose: To retrospectively analyze clinical features, laboratory investigations, treatment and visual outcomes in patients with tubercular subretinal abscess.Methods: A total of 12 eyes of 12 patients receiving a diagnosis of subretinal abscess, between 2004 and 2014, were included for this retrospective study.Results: The mean age of the presentation was 29.75 ± 16.72 years (range: 14-62 years) and seven (58.3%) were male. The most common anterior segment presentation was anterior uveitis (75%). The mean BCVA at presentation was 1.62 (in logMAR). A tuberculin skin test was positive in seven patients (58.3%) and five patients had a history of pulmonary tuberculosis. Polymerase chain reaction for the Mycobacterium tuberculosis genome was positive in 6 of 11 eyes from aqueous aspirate (54%) and 4 of 7 eyes from vitreous aspirates (57.14%). All patients were started on systemic steroids and an anti-tubercular regimen. The mean duration of follow-up was 134.28 days. The mean BCVA at final presentation was 1.19 (in logMAR). Chorioretinal scar was the most common finding after resolution.Conclusions: Subretinal abscess is a rare manifestation of ocular tuberculosis. A high degree of suspicion and timely management of the condition can prevent loss of vision. [ABSTRACT FROM AUTHOR]

A series of pyridine clubbed 1,3,4-oxadiazole derivatives were efficiently synthesized, characterized by standard spectral techniques and evaluated for theirin vitroantitubercular activity againstMycobacterium tuberculosis(MTB) H37Ra andMycobacterium bovisBCG in active and dormant state using an established methods. Compounds5a, 5m, and5twere identified as the most active compounds against MTB. Molecular docking was performed against MTB enoyl-ACP (CoA) reductase (FabI/ENR/InhA) enzyme to predict the binding modes and affinity. The theoretical predictions from molecular docking could establish a link between the observed biological activity and the binding affinity shedding light into specific bonded and non-bonded interactions influencing the activity. The active compounds were studied for cytotoxicity against three cell lines and were found to be non-cytotoxic. Specificity of these compounds was checked by screening them for their antibacterial activity against four bacterial strains. [ABSTRACT FROM AUTHOR]

During the treatment of tuberculosis infection, oxidative stress due to anti-tubercular drugs may result in tissue inflammation. It was suggested that treatment with antioxidant drugs could be beneficial as an adjunct to anti-tuberculosis drug therapy. Recently our group has shown that severalC-glycosides are inhibitors ofMycobacterium tuberculosisβ-carbonic anhydrases (CAs, EC 4.2.1.1). In an effort to develop novel chemotherapeutic agents against tuberculosis, the anti-tubercular and antioxidant activities of a series ofC-glycosides containing the phenol or the methoxyaryl moiety were studied. Many compounds showed inhibition of growth ofM. tuberculosisH37Rv strain and good antioxidant ability. A glycomimetic incorporating the 3-hydroxyphenyl moiety showed the best activity profile and therefore this functionality represents lead for the development of novel anti-tubercular agents with dual mechanisms of action. [ABSTRACT FROM PUBLISHER]

We earlier reported thiophene-containing trisubstituted methanes (TRSMs) as novel cores carrying anti-tubercular activity, and identified S006-830 as the phenotypic lead with potent bactericidal activity against single- and multi-drug resistant clinical isolates ofMycobacterium tuberculosis(M. tb). In this work, we carried out additional synthesis of several TRSMs. The reaction scheme essentially followed the Grignard reaction and Friedel–Crafts alkylation, followed by insertion of a dialkylaminoethyl chain. We also performed microbiological evaluations includingin vitroscreening against the virulent strainM. tbH37Rv, cytotoxicity assessment in the Vero C-1008 cell line, and 3D-QSAR studies with comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). CoMFA and CoMSIA models yielded good statistical results in terms ofq2andr2values, suggesting the validity of the models. It was concluded that a para-substituted benzene ring with bulkier electron-donating groups and aminoalkyl chains are required for higher inhibitory capacity againstM. tuberculosis. We believe that these insights will rationally guide the design of newer, optimal, TRSMs. [ABSTRACT FROM AUTHOR]

Aim: To review the results of QuantiFERON TB gold (QFT-G) in our patient population of presumed ocular tuberculosis and the effect of antitubercular therapy (ATT) on the QFT-G result.Materials and Methods: Retrospective review of 82 cases of presumed ocular tuberculosis with a successful response to ATT and 6 months follow-up post-ATT. Appropriate statistical analysis was done for associations between QFT-G and independent variables. Pre-ATT QFT-G values were also compared to the post-ATT value.Results: There were no statistically significant differences in the results of QFT-G with age (0.635), gender (0.096), history of oral steroids (0.171), or type of uveitis (0.664). There was a statistically significant association between a positive QFT-G and serpiginous-like choroiditis (0.048). The majority of our patients had positive QFT even after completion of ATT but with a significant drop in the mean values post ATT (0.010).Conclusions: Our study shows significant association of positive QFT with serpiginous-like choroiditis and persistent positivity even after completion of ATT in majority of cases in our population. There was, however, a drop in the mean values of QFT-G post-ATT. [ABSTRACT FROM AUTHOR]

BackgroundA retrospective cohort study was carried out to compare the survival between smear-positive patients and smear-negative multidrug resistant tuberculosis (MDR-TB) patients hospitalised in a specialised TB hospital in Witbank, South Africa.MethodsA review of medical records of MDR-TB patients treated from 2001 to 2010 was carried out. Survival time was measured from a patient’s date of hospitalisation to the date when the patient died, was last treated at the hospital or the end of the study (whichever came first). All patients who were alive until the end of the study period or lost to follow-up were censored and those who died were considered as failures. Survival patterns were estimated using Kaplan Meier plots, log rank tests and life tables. Cox proportional hazards regression analyses were also conducted.ResultsThe mean age of the 442 MDR-TB patients in the study was 37.7 ± 11.2 years. The incidence rates of mortality were 13.4 and 43.9 per 1000 person-months for smear-negative and smear-positive MDR-TB patients, respectively. Cox proportional hazard regression showed that the predictors of death among MDR-TB patients include HIV co-infection (adjusted Hazard Rate, aHR = 1.89, 95% CI = 1.02–3.52), old age (above 60 years) (aHR = 2.05, 95% CI = 1.04–3.60) and smear positivity at diagnosis (aHR = 3.29, 95% CI = 2.39–4.64).ConclusionThe study showed that the probability of survival during the treatment is reduced in MDR-TB patients, who are smear-positive, HIV positive or older than 60 years. Special care should be given to these patients to improve survival. [ABSTRACT FROM PUBLISHER]

A new series of indolylhydrazones (6) and indole-based 4-thiazolidinones (7,8) have been designed, synthesized and screened forin vitroantitubercular activity againstMycobacterium tuberculosisH37Rv. 4-Thiazolidinone derivatives7g–7j,8g,8hand8jdisplayed notable antituberculosis (anti-TB) activity showing 99% inhibition at MIC values ranging from 6.25 to 25.0 µg/ml. Compounds7g,7h,7i,8hand8jdemonstrated anti-TB activity at concentrations 10-fold lower than those cytotoxic for the mammalian cell lines. The indolylhydrazone derivative6bhas also been evaluated for antiproliferative activity against human cancer cell lines at the National Cancer Institute (USA). Compound6bshowed an interesting anticancer profile against different human tumor-derived cell lines at sub-micromolar concentrations with obvious selectivity toward colon cancer cell line COLO 205. [ABSTRACT FROM AUTHOR]

BackgroundThe aim of this study was to evaluate the diagnostic accuracy of the GenoType MTBDRplusassay in detecting drug-resistant tuberculosis (DR-TB) by using acid-fast bacilli (AFB) smear-negative specimens with positive TB-PCR results.MethodsThe MTBDRplusassay was performed with 2 different categories of 117 samples, including AFB smear-positive specimens (n = 53) and AFB smear-negative specimens (n = 64), which exhibited positive TB-PCR results, at a single institution. The results were retrospectively compared with the results of the phenotypic drug susceptibility test (DST), for reference.ResultsA total of 105 tests were finally analyzed. Of these, 54 tests were conducted using AFB smear-negative specimens with positive TB-PCR results. The MTBDRplusassay for these 54 samples demonstrated a sensitivity of 100%, specificity of 98%, positive predictive value (PPV) of 75%, and negative predictive value (NPV) of 100% in detecting rifampicin resistance. With these same species, the sensitivity, specificity, PPV, and NPV values for the MTBDRplusassay were 83.3%, 97.9%, 83.3%, and 97.9%, respectively, for the detection of isoniazid resistance. The overall correlation between the MTBDRplusassay and phenotypic DST demonstrated excellent agreement for detection of rifampicin resistance (κ = 0.847) and for detection of INH resistance (κ = 0.812), respectively.ConclusionsThe MTBDRplusassay can be used effectively even on AFB smear-negative specimens from TB patients, when the TB-PCR is positive. This result might help clinicians to manage patients with suspected DR-TB in difficult situations. [ABSTRACT FROM AUTHOR]

The article discusses the challenge of diagnosis of ocular tuberculosis (TB) to ophthalmologists and physicians. Topics discussed include the prevalence of TB uveitis, a definitive diagnosis of TB uveitis and the advent of interferon gamma release assays (IGRA) which measures gamma response that sensitized T cells produce by Mycobacterium tuberculosis-specific antigens.

Tuberculosis, MTB or tubercle bacillus (TB) is a lethal, infectious disease mainly caused by various strains of mycobacteria, usuallyMycobacterium tuberculosis. In this study, guar gum-based porous nanoaggregates were formulated by precipitation technique with two frontline antitubercular drugs, i.e. isoniazid and rifampicin. The formulations were optimized on the basis of various evaluation parameters such as morphology, density, entrapment efficiency andin vitrodrug release. The optimized formulations were administered by inhalable route to Wistar rats for the evaluation of drugs in different organs (lungs, liver and kidneys). High drug encapsulation efficiency was achieved in guar gum porous nanoaggregates, ranging from 50% to 60%. A single pulmonary dose resulted in therapeutic drug concentrations of 30%–50% in the lungs and in other organs (less than 5%) for 24 h. From this study, we can conclude that delivering drugs through pulmonary route is advantageous for local action in lungs. Furthermore, the formulation showed sustained drug release pattern, which could be beneficial for reducing the drug dose or frequency of dosing, thus helpful in improving patient compliance. [ABSTRACT FROM AUTHOR]

Background: This study estimated the incidence of progression to active tuberculosis (TB) among contacts categorized by QuantiFERON(®)-TB Gold in Tube (QFT-GIT) test results and investigated other risk factors related to progression to TB. Methods: Contacts of patients with TB were tested using QFT-GIT and were followed up every 6 months at public health centers to detect clinical progression to TB. Results: Analysis of a retrospective cohort revealed that, of the 625 contacts, 168 were QFT-GIT positive and 457 were negative. Of these, 10 (6%) QFT-GIT-positive and two (0.4%) QFT-GIT-negative contacts progressed to TB during the follow-up period (p < 0.01, statistically significant). Multivariable logistic regression analysis revealed that QFT-GIT positivity (p < 0.01), contact of index patients with many other positive contacts (p < 0.01), household contact (p = 0.014), and untreated latent TB infection (p = 0.047) were independent risk factors for progression to TB during an average follow-up period of 637 days. Conclusions: Progression to TB among QFT-GIT-positive contacts was higher than among QFT-GIT-negative contacts. Other independent risk factors for progression to TB were index cases with more QFT-GIT-positive contacts as well as household contacts. [ABSTRACT FROM AUTHOR]

Background: Interferon- release assays (IGRAs) are increasingly used for the diagnosis of latent tuberculosis infection (LTBI). Because of the lack of a gold standard for the diagnosis of LTBI, IGRAs are compared to the tuberculin skin test (TST) and yield conflicting results. We assessed the usefulness of an IGRA test, QuantiFERON® -TB Gold In-Tube (QFTG- IT), for diagnosing LTBI compared with TST in the setting of a contact screening study. Methods: A prospective comparison between the QFT-G-IT and the TST in TB contact subjects in a low TB burden area was conducted sequentially between January 2006 and December 2012. Results: A moderate concordance between the two tests (κ = 0.44 for TST cut-off of 5 mm and κ = 0.56 for TST cut-off of 15 mm) was found. A better agreement was shown in younger contacts and in non-vaccinated contacts when using a TST of 15 mm. Independent risk factors for a TST+/QFT-G-IT - discordance were history of BCG vaccination and age between 31 and 59 years. Discordance was also more frequent using a TST cutoff value of 5 mm. QFT-G-IT+ /TST - was infrequent and was found in older contacts. Conclusions: Based on our data, we cannot recommend the use of QFT-G-IT as the only test to rule out LTBI, especially in older patients. [ABSTRACT FROM AUTHOR]

Background: Human immunodeficiency virus (HIV)-infected individuals are at high risk of contracting tuberculosis (TB) disease, and current methods for diagnosing TB infection are less effective in this population. We developed and evaluated a new interferon-gamma release assay (IGRA), named A.TB, in HIV-infected individuals, with and without active TB, in a setting of high TB burden and low HIV prevalence. Methods: A total of 255 subjects were divided into 3 groups according to their HIV and TB status: HIV + without active TB (n = 123), HIV +/TB + (n = 79), and HIV-/TB + (n = 65). The A.TB assay was performed in parallel with the QuantiFERON-TB Gold In-Tube (QFT-GIT) and tuberculin skin test (TST). Results: The positive rate was 59.3% (n = 123) by A.TB and 53.8% (n = 106) by QFT-GIT. We observed a strong concordance of 81.2% (k = 0.612) between the two IGRAs. The QFT-GIT results were affected by low CD4+ cell count (p= 0.013), while A.TB results were not. A.TB was also performed in patients with active TB (n = 65) and patients with active TB and HIV co-infection (n = 79). The sensitivity of A.TB in these groups was 80.0% and 81.0%, respectively. Conclusion: The A.TB results were not affected by low CD4+ cell count in the co-infected cohort. With further evaluation,A.TB may prove to be a valuable tool for diagnosing TB in HIV-infected patients. [ABSTRACT FROM AUTHOR]

In a quest for developing novel anti-tubercular agents, a series of 3-benzylidene-4-chromanones 1a- l were evaluated for growth inhibition of Mycobacterium tuberculosis H37Rv. Three promising compounds 1d, g, j emerged as the lead compounds with the IC50 and IC90 values of less than 1 µg/mL. Evaluation of the potent compounds 1d, g, j and k against Vero monkey kidney cells revealed that these compounds are far more toxic to M. tuberculosis than to Vero cells. Structure-activity relationships demonstrated that 3-benzylidene-4-chromanones are more potent against M. tuberculosis than the related 2-benzylidene cycloalkanones and the meta substituted chromanone derivatives are more active than their ortho- and para-counterparts. Some guidelines for amplifying the project are presented. [ABSTRACT FROM AUTHOR]

Background: Mycobacterium tuberculosis (TB) is a rare cause of prosthetic joint infection. The purpose of this study was to provide an evidence-based summarization of the outcomes of TB infection after total knee arthroplasty (TKA) with a pooled analysis of the reported cases. Methods: We conducted a systematic review of published studies that have evaluated the outcomes of prosthetic knee joint infections due to TB. A structured literature review of multiple databases referenced articles from January 1950 to July 2012. Results: A total of 15 patients were identified from 13 published studies. Tuberculosis was confirmed in all cases by histological examination and positive culture or histochemical stain/polymerase chain reaction (PCR). Treatment consisted of anti-tuberculosis medication therapy (AMT) only in 2 patients, AMT plus debridement and retention of the arthroplasty in 5 patients, and AMT plus removal/exchange of the arthroplasty in 8 patients. The average follow-up after TB infection was 29 months (range 1-96 months) and there were 3 deaths, giving a crude death rate of 0.7 per 100 person-months. At the final follow-up, the outcomes of TB infection after TKA were good except in the 3 patients who died. Conclusions: TB infection after TKA is a rare disease, however good clinical outcomes can be achieved with proper management including AMT and surgical intervention. [ABSTRACT FROM AUTHOR]

Conclusion: The necessity of considering cervical tuberculous lymphadenitis (CTL) should be emphasized even today for the differential diagnosis of cervical lymphadenopathy, particularly when it is located in the posterior triangle and supraclavicular regions even in patients without active pulmonary tuberculosis (PTB). Objective: This study was conducted to highlight the characteristics of patients with CTL without active PTB who were treated in our department. Methods: Between 2004 and 2011, 21 cases of CTL without active PTB were included in this retrospective study. Histological examination after excisional biopsy of the affected lymph node was performed in 18 patients using hematoxylin and eosin staining and Ziehl-Neelsen (Z-N) staining for acid-fast bacilli (AFB) identification. Growth of Mycobacterium tuberculosis was detected by culturing and/or nucleic acid amplification tests including polymerase chain reaction (PCR) and transcription-mediated amplification (Mycobacterium Tuberculosis Direct: MTD). Results: The male to female ratio was 1:1.3. Patient ages ranged from 22 to 89 years. Eighteen patients (85.7%) complained of indolent unilateral cervical lymphadenopathy in the posterior triangle (26.5%), internal jugular (24.5%), or supraclavicular nodes (18.4%). Positive rates of AFB according to Z-N staining and culturing of M. tuberculosis and/or PCR or MTD were 33.3% (6/18) and 72.2% (13/18), respectively. [ABSTRACT FROM AUTHOR]

A series of novel Mannich bases of chlorokojic acid (2-chloromethyl-5-hydroxy-4 H-pyran-4-one) were synthesized and their biological activities were investigated. Anticonvulsant activity results according to phase-I tests of Antiepileptic Drug Development (ADD) Program revealed that compound 13 was the most effective one at 4 h against subcutaneous pentylenetetrazole (scPTZ)-induced seizure test. Antimicrobial activities were evaluated in vitro against bacteria and fungi by using broth microdilution method. The antitubercular activities against Mycobacterium tuberculosis and M. avium were discussed with Resazurin microplate assay (REMA). The antimicrobial activity results indicated that compounds 1 and 12 (MIC: 8-16 µg/mL) showed higher activity against Gram negative bacteria while compound 12 had MIC: 4-16 µg/mL against Gram positive bacteria. Compound 1 was the most active one with MIC values of 8-32 µg/mL against fungi. Mannich bases also exhibit significant antitubercular activity in a MIC range of 4 to 32 µg/mL, especially compound 18 against M. avium. [ABSTRACT FROM AUTHOR]

Context: Eucalyptus camaldulensis Dehnh. (Myrtaceae) and Eucalyptus torelliana F. Muell are used in Nigerian traditional medicine for the treatment of cough associated with tuberculosis (TB) and other respiratory infections. Objective: Hexane, chloroform, methanol extracts, and isolated compounds of E. camaldulensis and E. torelliana were screened for activity against Mycobacterium tuberculosis H37Rv (MtbH37Rv) to authenticate the traditional use of these plants. Materials and methods: The microplate alamar blue assay (MABA) method was used to investigate the anti- M. tuberculosis activities. Bioassay-guided fractionation of the hexane extract of E. torelliana leaf was performed, and isolated compounds were characterized by MS, 1D- and 2D-NMR. Results: The extracts inhibited the growth of MtbH37Rv [minimum inhibitory concentration (MIC) 4-64 µg/mL]. Spectroscopic characterization led to the identification of two compounds, hydroxymyristic acid methylester ( 1) and a substituted pyrenyl ester, a sterol ( 2). Compounds 1 and 2 had MIC of 49.45 and 46.99 µg/mL; IC50 >100 and 38.21 µg/mL; selectivity index (SI) >2.02 and 0.81, respectively, and a minimum bactericidal concentration (MBC) of 62.50 µg/mL. Discussion and conclusions: The anti-TB activities of these plants on M. tuberculosis H37Rv support their use in traditional medicine for the treatment of coughs associated with TB and reveals the presence of anti- Mtb active compounds in the plants. These findings not only demonstrate a new potential area of therapeutic value of E. camaldulensis and E. torelliana, but also illustrate the role of esters as anti- Mtb active principles in ethnobotanical preparations and as lead compounds in the development of new and effective anti- Mtb drugs. [ABSTRACT FROM AUTHOR]

Isoniazid (INH) is a first line drug for treatment of the widespread deadly disease caused by Mycobacterium tuberculosis. Peptide conjugate of INH was designed and synthesised for targeted and receptor mediated cellular uptake of INH. Chemical composition, hydrophobicity (n-octanol/water partition coefficient), and membrane affinity (using a Langmuir lipid monolayer as a model system) of the conjugate were characterised. Hydrophilicity of the drug was remarkably decreased by the conjugation which resulted in improved interaction with lipid layer and allowed its efficient encapsulation into polylactic/glycolic acid nanoparticles enhancing the bioavailability of the drug. [ABSTRACT FROM AUTHOR]

Cutaneous tuberculosis is showing a resurgence. It continues to be one of the most elusive and difficult diseases to diagnose in dermatological practice. We sought to describe the clinical manifestations, laboratory features, and antituberculous therapy in cases of cutaneous tuberculosis. Twenty cases of cutaneous tuberculosis were observed in this study. Of the 20 cases, seven were in women (35%) and 13 were in men (65%). There were eight (40%) cases of lupus vulgaris, four (20%) cases of orificial tuberculosis, four (20%) cases of tuberculosis verrucosa cutis, two (10%) cases of scrofuloderma, and two (10%) cases of primary inoculation tuberculosis. In total, 20 strains of acid-fast bacilli were isolated by culture in Löwenstein-Jensen medium at 37°C. Mycobacterial species identification by polymerase chain reaction (PCR) assay showed that all strains were Mycobacterium tuberculosis. In vitro susceptibility testing by use of absolute concentration method showed that the 20 strains were sensitive to rifampin, ethambutol, and isoniazid; however, two strains were resistant to streptomycin. All of the patients responded favourably to antituberculous treatment. Cutaneous tuberculosis is a skin disease that should still be thought much of in mainland China, and in this study lupus vulgaris is the most common clinical presentation. [ABSTRACT FROM AUTHOR]

Fourteen 5-nitro-2,6-dioxohexahydro-4-pyrimidinecarboxamides ( 3a-n) were synthesized and evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB), multidrug-resistant Mycobacterium tuberculosis (MDR-TB), and Mycobacterium smegmatis (MC2), as well as their cytotoxicity and MTB isocitrate lyase (ICL) inhibition activity. 1-Cyclopropyl-6-fluoro-8-methoxy-7-(3-methyl)-4-[(5-nitro-2,6-dioxohexahydro-4-pyrimidinyl)carbonyl]piperazino-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid ( 3n) was found to be the most active compound in vitro with MICs of < 0.17 and 0.17 μM against log-phase MTB and MDR-TB, respectively. Some compounds showed 20-45% inhibition against MTB ICL at 10 μM. [ABSTRACT FROM AUTHOR]

Despite being an ancient disease, tuberculosis (TB) remains the leading single-agent infectious disease killer in the world. The emerging serious problem of TB control and clinical management prompted us to synthesize a novel series of heterocyclic substituted diphenyl ether derivatives and determine their activity against the H37Rv strain of Mycobacterium. All ten compounds inhibited the growth of the H37Rv strain of Mycobacterium at concentrations of 1 μg/mL. This activity was found to be comparable to the reference drugs rifampicin and isoniazid at the same concentration. While the antimicrobial activity of other diphenyl ether analogues, such as triclosan, is associated with the inhibition of enoyl-ACP reductase (ENR), the synthesised substituted diphenyl ether derivatives did not affect this enzyme activity in spite of their structural similarity with triclosan. Therefore, these compounds appear to have a novel mechanism of action against M. tuberculosis, and their structural features should be studied further for their potential as new antitubercular drugs. [ABSTRACT FROM AUTHOR]

Conclusion: The standard treatment for tuberculous otitis media (TOM) without complications consists of anti-tuberculosis (anti-TB) medication, with which we experienced good treatment outcomes. However, surgery is required for recovery of anatomy and hearing function. Objective: To determine the clinical characteristics of TOM that might optimize diagnosis and to evaluate the differences in clinical courses between patients treated with and without surgery. Methods: We analyzed 14 patients (16 ears) who had been diagnosed and treated for TOM. Radiologic findings, laboratory data, and audiometry results were also evaluated. Patients were divided into a chemotherapy group and a surgery group according to treatment modality. Results: Temporal bone CT (TBCT) showed total occupation of the tympanic cavity by soft tissue and little evidence of ossicular erosion. In the chemotherapy group, dry ears were obtained in all but one patient (14 ears) after treatment. Normalized tympanic membrane (TM) was found in 50% in the chemotherapy group and in 75% in the surgery group. The air–bone gap (ABG) changed from 40.3 ± 2.5 dB to 47.0 ± 19.2 dB in the chemotherapy group and from 35.2 ± 7.6 dB to 30.2 ± 11.4 dB in the surgery group. After treatment, ABG improved by > 10 dB in one ear in the chemotherapy group and in four ears in the surgery group. [ABSTRACT FROM AUTHOR]

To study the possible importance of mycobacterial ES-31 serine protease for bacterial cell growth, the effect of serine and metalloprotease inhibitors, anti-tubercular drugs such as isoniazid and anti-ES-31 antibody, was evaluated on mycobacterial ES-31 serine protease in vitro and on bacilli in axenic and macrophage cultures. Serine protease inhibitors such as pefabloc, 3,4 dichloroisocoumarin, phenyl methyl sulfonyl fluoride (PMSF) and metalloprotease inhibitors such as ethylene diamine tetracetic acid (EDTA) and 1,10 phenanthroline inhibited 65-92% serine protease activity in vitro. Isoniazid showed 95% inhibition on mycobacterial ES-31 serine protease. These inhibitors also showed decreased bacterial growth in axenic culture and inhibition was further confirmed by a decreased amount of ES-31 serine protease in culture filtrate. In human macrophage culture, highly inhibitory pefabloc, 1,10 phenanthroline and isoniazid inhibited infectivity of virulent as well as avirulent M. tuberculosis bacilli to macrophages. It was observed that addition of mycobacterial ES-31 serine protease to macrophage culture enhanced the entry of bacilli and their multiplication in human macrophages. However, the addition of anti-ES-31 serine protease antibody strongly inhibited the mycobacterial growth as observed by decreased CFU count, showing the importance of mycobacterial ES-31 serine protease for entry of bacilli and their multiplication. [ABSTRACT FROM AUTHOR]

The synthesis of a new series of imidazo[1,2-a]pyrazine-2-carboxylic acid arylidene-hydrazides is described. The chemical structures of the compounds were elucidated by IR, 1H-NMR, FAB+-MS spectral data. Their biological activity against various bacteria, fungi species, and Mycobacterium tuberculosis was investigated. Antibacterial activity was measured against Escherichia coli (NRRL B-3704), Staphylococcus aureus (NRRL B-767), Salmonella typhimurium (NRRL B-4420), Proteus vulgaris (NRLL B-123), Enterococcus faecalis (isolated obtained from Faculty of Medicine Osmangazi University, Eskisehir, Turkey), Pseudomonas aeruginosa (NRRL B-23 27853), Klebsiella spp. (isolated obtained from Faculty of Medicine Osmangazi University, Eskisehir, Turkey), while antifungal activity was evaluated against Candida albicans (isolates obtained from Osmangazi Uni. Fac.of Medicine), Candida glabrata (isolates obtained from Osmangazi Uni. Fac.of Medicine). Compounds were also evaluated for antituberculosis activity against Mycobacterium tuberculosis H 37 Rv using the BACTEC 460 radiometric system and BACTEC 12B medium. The compounds showed moderate inhibitor effects against human pathogenic microorganisms., whereas the preliminary results indicated that all of the tested compounds were inactive against Mycobacterium tuberculosis H37Rv. [ABSTRACT FROM AUTHOR]

Fujita-Ban, Hansch substituent constants, topological descriptors and conformational dependent descriptors were explored for quantification of anti-tubercular activity of N-hydroxythiosemicarbazone analogs. All the approaches gave statistically sound model which accounts for more than 88% of the explain variance against anti-tubercular activity except Fujita-Ban (∼75%). Fujita-Ban & Hansch approaches having certain limitation, however, another approache showed their significant role in explaining activity of the modified scaffolds. QSAR study of N-Hydroxythiosemicarbazone analogs furnished some important structural insights i.e., the R position is more prone for improving inhibitory activity and the R1 position play a decisive role in the ionic interaction of the ligand with macromolecules. On the basis of findings, N-hydroxythiosemicarbazones interaction model with macromolecule of M. Tuberculosis has been proposed. These interactions might be helpful in further development of potent anti-tubercular agents. [ABSTRACT FROM AUTHOR]

A series of nine polypyridyl-ruthenium (II) complexes (N-ligands = 2,2'-bipyridines; 2,2'-6',2'-terpyridines, di-alkyloxy-2,2'-6,2-bipyridine-3,3'-di-carboxylates), were tested against Mycobacterium tuberculosis (MBT). The complex (11) showed remarkable activity against MBT as compared to other complexes, (1-10). The aquo ligand of complex (11), as opposed to other chloro and acetonitrile derivatives, appears to play a key role in the antitubercular potency of this new class of metal-based compounds. [ABSTRACT FROM AUTHOR]

The global spread of tuberculosis (TB) has been fuelled by the development of strains of the causative bacterium (Mycobacterium tuberculosis, Mtb) that are resistant to all the leading drugs. New TB therapies are desperately needed, but recent genome sequence, genetic and protein characterization studies have helped identify novel Mtb drug targets and key biochemical pathways for strategic intervention. Of particular interest are the multiple cytochrome P450 (P450) enzymes encoded in the Mtb genome. Structural, biochemical and mechanistic studies on these systems have demonstrated their potential as antitubercular targets, as well as revealing novel aspects of P450 form and function. [ABSTRACT FROM AUTHOR]

Thiocarlide (THC; N,N'-bis[p-(isoamyloxy)phenyl]-thiourea; also known as Isoxyl®) has been used in the past as an anti-tuberculosis agent. In an effort to improve the therapeutic value of THC, several N-glycosyl-N'-[p-(isoamyloxy)phenyl]-thiourea derivatives were synthesized by coupling an aniline derivative and glycosyl isothiocyanates. The minimum inhibitory concentration (MIC) values of the new products against M. tuberculosis were determined. [ABSTRACT FROM AUTHOR]

The recent increase in the incidence of tuberculosis with the emergence of multidrug-resistant (MDR) cases has lead to the search for new drugs that are effective against MDR strains of Mycobacterium tuberculosis and can augment the potential of existing drugs against tuberculosis. Pelargonium sidoides DC (Geraniaceae) is highly valued by traditional healers for its curative properties and is well-known to treat coughs, diarrhea, and tuberculosis. The butanol root extract was found have bioactive inhibitory activity against M. tuberculosis at a concentration of 2.5 × 103 µg/mL. Phytochemical analysis of the active fraction from the root of P. sidoides led to the isolation and identification of six compounds: coumarins (umckalin, scopoletin, 6,8-dihydroxy-5.7-dimethoxy-2H-benzopyran-2-one, and 6,8-dihydroxy-7-methoxy-2H-benzopyran-2-one) and flavonoids (catechin and epigallocatechin, which is reported for the first time from P. sidoides). The isolated compounds were evaluated for antitubercular activity with M. smegmatis and M. tuberculosis. Intracellular activity of these compounds was also investigated using THP-1 human macrophages infected with M. tuberculosis. The isolated compounds did not show activity inhibitory against M. tuberculosis, intracellularly and extracellularly, at the highest concentration tested in the current study. Epigallocatechin and scopoletin showed good inhibitory activity against M. smegmatis, exhibiting a minimum inhibitory concentration (MIC) of 7.8 µg/mL. Catechin and umckalin exhibited MIC values of 31.25 and 62.5 µg/mL, respectively. [ABSTRACT FROM AUTHOR]

A series of, anilino-5- (substituted) phenyl -3-(4-hydroxy-3-methylphenyl)-4,5-dihydro-1H-1-pyrazolylmethanethione and 2-chloroanilino-5- (substituted) phenyl -3-(4-hydroxy-3-methylphenyl)-4,5-dihydro-1H-1-pyrazolylmethanethione were synthesized by the reaction between hydrazine hydrate and the chalcones (3a-k) followed by condensation with the appropriate aryl isothiocyanate which yielded the N-substituted pyrazoline derivatives. These were tested for their in-vitro anti-mycobacterial activity against INH resistant Mycobacterium tuberculosis (INHR MTB) using the BACTEC 460 radiometric system. Compound 2-chloroanilino-5-(2,6-dichlorophenyl)-3-(4-hydroxy-3-methylphenyl)-4,5-dihydro-1H-1-pyrazolylmethanethione (6i) was found to be most active agent with a minimum inhibitory concentration of 0.96μg/mL. [ABSTRACT FROM AUTHOR]

A series of 2,6-disubstituted imidazo[2,1-b][1,3,4]thiadiazoles, their new Mannich bases and novel benzothiazole derivatives were synthesized. The structures of all the synthesized compounds were established by analytical and spectral data. All the compounds were screened for their antitubercular activity against Mycobacterium tuberculosis H37Rv using the BACTEC 460 radiometric system and antibacterial activity against E. coli and B. cirrhosis, antifungal activity against A. niger and P. worthmanni. Among the tested compounds Mannich bases 3e, 3f and 4 g and 5-carbaldehyde derivative 6d have shown excellent inhibition (99, 99, 97 and 95%, respectively) against M. tuberculosis. Mannich bases in general have also shown impressive antifungal activity. [ABSTRACT FROM AUTHOR]

Rapid and efficient diagnosis is essential in the management of drug‐resistant tuberculosis. A DNA microarray technique based on differential hybridization method was described in the present study for detecting mutations in the RNA polymerase beta subunit ( rpoB ) gene of Mycobacterium tuberculosis ( M. tuberculosis ) cultures and in clinical specimens. The mutations in rpoB confer resistance to rifampin, an important first‐line antituberculosis drug. The differential hybridization approach was mainly based on the effect of a single base mismatch on the melting temperature of the hybridized DNA; therefore, any point mutation of rpoB gene resulting in the rifampin resistance can be detected efficiently. The development of the DNA microarray involves the design of dozens of oligonucleotide probes for identifying rifampin‐resistant and ‐sensitive strains. The method comprises isolating genomic DNA from the samples containing M. tuberculosis cells, amplifying rpoB gene coding sequence to produce fluorescently labelled product, and hybridization with the oligonucleotide arrays. The results demonstrated the capability of DNA microarray to provide important clinically relevant information about the rpoB gene of mycobacterial organisms. The DNA microarray offers a reliable diagnostic test for rapidly detecting multidrug resistance caused by gene mutations of mycobacteria. [ABSTRACT FROM AUTHOR]

The extent of drug resistant tuberculosis (TB) in the capital city of Myanmar, Yangon has not yet been reported. This study aimed to determine the proportion and pattern of drug resistance to first-line anti-TB drugs, among Mycobacterium tuberculosis complex isolates from sputum smear positive TB patients who attended National TB Programme Yangon centres in April–August and October–December 2002. Drug susceptibility was determined by the Mycobacteria Growth Indicator Tube manual system (Becton Dickinson, MD, USA). Of the 567 patients, sputum specimens from 447 (79%) had a positive culture. Of these, 357 isolates (80%) had a susceptibility test result. Isolates from 76 of 259 (29.3%) new patients and from 45 of 98 (45.9%) previously treated patients were resistant to at least 1 of the anti-TB drugs. Resistance to isoniazid (INH) (22.0% vs 40.8%: new vs previously treated patients) and to ≥2 drugs (17.8% vs 29.6%: new vs previously treated patients) was common. Multidrug- resistant TB (MDR-TB) among new and previously treated patients was 4.2% and 18.4%, respectively. INH-resistant (adjusted OR: 2.0, 95% CI 1.1–3.6) and MDR-TB (adjusted OR: 3.4, 95% CI 1.4–8.3) cases were more likely to have taken anti-TB drugs ≥1 month previously. Collectively, prevalence of MDR-TB and TB resistance to ≥2 drugs are not rare in Yangon. [ABSTRACT FROM AUTHOR]

New pyrrolo[1,2-α]quinoxaline-2- or -4-carboxylic acid hydrazide derivatives were synthesized from nitroaniline or 1,2-phenylenediamine, and evaluated in vitro for their antimycobacterial activity as part of a TAACF TB screening program. Two compounds 7c and 13 showed an interesting activity at 6.25 µg/mL against Mycobacterium tuberculosis H37RV, with a 94 and 100 percentage inhibition, respectively. [ABSTRACT FROM AUTHOR]