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Vanessa Clifford, Marc Tebruegge, Christel Zufferey, Susie Germano, Ben Forbes, Lucy Cosentino, Elizabeth Matchett, Emma McBryde, Damon Eisen, Roy Robins-Browne, Alan Street, Justin Denholm, Nigel Curtis
OBJECTIVE: Accurate and timely diagnosis of tuberculosis (TB) is essential to control the global pandemic. Currently available immunodiagnostic tests cannot discriminate between latent tuberculosis infection (LTBI) and active tuberculosis. This study aimed to determine whether candidate mycobacterial antigen-stimulated cytokine biomarkers can discriminate between TB-uninfected and TB-infected adults, and additionally between LTBI and active TB disease. METHODS: 193 adults were recruited, and categorised into four unambiguous diagnostic groups: microbiologically-proven active TB, LTBI, sick controls (non-TB lower respiratory tract infections) and healthy controls...
January 2019: Tuberculosis
Cheh Tat Law, Frank Camacho, Luis F Garcia-Alles, Martine Gilleron, Maria E Sarmiento, Mohd Nor Norazmi, Armando Acosta, Yee Siew Choong
Tuberculosis (TB) is the main cause of mortality among all infectious diseases. The presentation of lipids by CD1b molecules and the interactions of the CD1b-lipid complexes with the immune receptors are important for the understanding of the immune response to Mycobacterium tuberculosis (Mtb), and to develop TB control methods. A specific domain antibody (dAbk11) recognizing the complex of CD1b with Mtb sulphoglycolipid (Ac2 SGL) had been previously developed. In order to study the interactions of dAbk11 with Ac2 SGL:CD1b, the conformation of Ac2 SGL within CD1b was first modelled...
January 2019: Tuberculosis
Elena Ufimtseva, Natalya Eremeeva, Sergey Bayborodin, Tatiana Umpeleva, Diana Vakhrusheva, Sergey Skornyakov
Tuberculosis (TB) is a dangerous airborne disease caused by Mycobacterium tuberculosis (Mtb) and characterized by a tight interplay between pathogen and host cells, mainly alveolar macrophages. Studies of the mechanisms of Mtb survival within human cells during TB disease are extremely important for the development of new strategies and drugs for TB treatment. We have used the ex vivo cultures of alveolar macrophages and histological sections obtained from the resected lungs of patients with pulmonary TB to establish the unique features of Mtb lifestyle in host cells...
January 2019: Tuberculosis
Elvis Ndukong Ndzi, Céline Nguefeu Nkenfou, Linda Mouafo Mekue, Lorena Zentilin, Ousman Tamgue, Eric Walter Yone Pefura, Jules-Roger Kuiaté, Mauro Giacca, Alexis Ndjolo
The diagnosis of tuberculosis (TB) continues to pose substantial public health problems. The quest for diagnostic biomarkers for TB is therefore primordial. This study aimed to evaluate the diagnostic and anti-TB treatment monitoring potentials of some selected miRNAs. Quantitative real time polymerase chain reaction and Receiver operating characteristics were used to estimate the ability of miRNAs to discriminate between healthy controls (HEC), latent (LTB) and active TB (ATB). The study showed that: hsa-miR-29a-3p, hsa-miR-155-5p and hsa-miR-361-5p were significantly upregulated in ATB compared to HEC while hsa-miR-29a-3p, and hsa-miR-361-5p were also significantly up-regulated in ATB compared to LTB (all P ≤ 0...
January 2019: Tuberculosis
Yves Ira A Reyes, Gerardo C Janairo, Francisco C Franco
Isoniazid (INH) is known to cause the exclusive lethal action to Mycobacterium tuberculosis (M. tb.) cells because of the pathogen's own catalase-peroxidase (katG) enzyme that converts INH to a very reactive radical. Thus, in order to gain insights on the interaction of INH with the individual active site residues (Res) of katG, this study presents a computational approach via molecular docking and density functional theory (DFT) using augmented models to study the individual INH-Res interactions. Seven amino acid residues directly interacts with INH: Arg104, Asp137, His108, Ile228, Trp107, Tyr229, and Val230...
January 2019: Tuberculosis
Agumas Shibabaw, Baye Gelaw, Holden Kelley, Joan Miquel Balada-Llasat, Carlton Evans, Shu-Hua Wang, Jordi B Torrelles, Belay Tessema
BACKGROUND: Accurate and timely tuberculosis diagnosis is the primary step for initiating effective treatment. The color plate agar-based culture test (TB-CX test) is low cost, simple to use and detects Mycobacterium tuberculosis faster. Therefore, the main objective of this study was to compare the diagnostic accuracy and time to detection of positive cultures using color test and Lӧwenstein Jensen culture. METHODS: A comparative cross-sectional study was conducted at University of Gondar Hospital...
January 2019: Tuberculosis
Megan Fitzpatrick, Mei Mei Ho, Simon Clark, Belinda Dagg, Bhagwati Khatri, Faye Lanni, Ann Williams, Michael Brennan, Dominick Laddy, Barry Walker
A global BCG vaccine shortage began in 2013 which impacted availability for infant vaccinations, as well as preclinical studies and clinical trials of new TB vaccines. Stakeholders met in 2015 at McGill University in Montreal to discuss the shortage and potential mitigation strategies. Manufacturing BCG through a more tractable liquid fermentation process instead of the traditional pellicle growth method was considered a potentially viable strategy. This pilot program compared pellicle-grown and shake flask-grown BCG strains (as a first step towards modeling fermenter-produced BCG vaccine) in selected quality control assays, as well as mouse and guinea pig protection studies...
January 2019: Tuberculosis
Orawan Tulyaprawat, Angkana Chaiprasert, Piriyaporn Chongtrakool, Kamol Suwannakarn, Popchai Ngamskulrungroj
Ethambutol (EMB) is the first-line antituberculosis drug and a potential supplementary agent for a treatment regimen of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). It has long been known that mutations in embCAB operon, encoding EMB target, arabinosyltransferase, confer resistance to EMB. Recently, ubiA was additionally reported to be specifically associated with high-level EMB resistance in Mycobacterium tuberculosis. However, such information on ubiA is very limited. This study aimed to investigate correlations between mutations in ubiA and phenotypic EMB resistance among EMB-resistant (EMBR ) M...
January 2019: Tuberculosis
Danilo Pires Resende, Adeliane Castro da Costa, Lorena Pereira de Souza Rosa, Ana Paula Rodrigues, Annelise Silva E Alvez Santos, Camila Kellen Cardoso, Jaqueline Danesio Sousa, André Kipnis, Erika Aparecida Silveira, Ana Paula Junqueira-Kipnis
Severe obesity and diabetes lead to a significant decrease in quality of life. Although controversial, population-wide studies have implicated obesity in the development of tuberculosis (TB). Non-classical monocytes have been described in obesity and TB, whereas in diabetes they have been associated with poorer clinical outcomes. The present study focuses on the functional significance of several monocyte populations of obese, obesity-related diabetic (OBDM), non-obese/diabetic tuberculosis and non-obese healthy control patients...
January 2019: Tuberculosis
Piotr Korczynski, Joanna Klimiuk, Aleksandra Safianowska, Rafal Krenke
The diagnostic value of pleural fluid biomarkers in tuberculous pleurisy (TP) is firmly established. However, it is less clear whether patients' age affects the diagnostic accuracy of TP biomarkers. The aim of the study was to assess the impact of age, on the predictive value of ADA, IFN-γ, IP-10 and Fas ligand in patients with pleural effusion. The study included 222 patients, median age 64.5 (54-77) years, 58.6% men, with pleural effusion: TPE (60 patients; 27.0%), malignant PE (90 patients; 40.5%), parapneumonic effusion/pleural empyema (35 patients; 15...
January 2019: Tuberculosis
Vera V Ustinova, Tatiana G Smirnova, Dmitry G Sochivko, Dmitry A Varlamov, Elena E Larionova, Sofya N Andreevskaya, Irina Yu Andrievskaya, Ekaterina A Kiseleva, Larisa N Chernousova, Atadzhan Ergeshov
The purpose of the present study was to create a real-time PCR test system allowing simultaneous detection of nontuberculous mycobacteria (NTM) and Mycobacterium tuberculosis complex (MTBC) both in culture and sputum. NTM cultures (18 strains, 18 species), MTBC cultures (16 strains, 2 species) and non-mycobacterial microorganisms from the collection of the Central Research TB Institute (CTRI) were used for the preliminary evaluation of the test system. 301 NTM cultures from patients with mycobacteriosis were used to assess the sensitivity of the developed test system...
January 2019: Tuberculosis
Caroline Busatto, Júlia Silveira Vianna, Lande Vieira da Silva, Ivy Bastos Ramis, Pedro Eduardo Almeida da Silva
Mycobacterium avium is an environmental microorganism found in soil and water sources worldwide. It is the most prevalent species of nontuberculous mycobacteria that causes infectious diseases, especially in immunocompromised individuals. This review discusses and highlights key topics about M. avium, such as epidemiology, pathogenicity, glycopeptidolipids, laboratory identification, genotyping, antimicrobial therapy and antimicrobial resistance. Additionally, the main comorbidities associated with M. avium infection are discussed...
January 2019: Tuberculosis
Erik Nieto-Patlán, Jeanet Serafín-López, Isabel Wong-Baeza, Sonia M Pérez-Tapia, Laura Cobos-Marín, Sergio Estrada-Parra, Iris Estrada-García, Alma D Chávez-Blanco, Rommel Chacón-Salinas
Tuberculosis is one of the leading causes of mortality worldwide, it is caused by Mycobacterium tuberculosis (Mtb), a bacteria that employs several strategies to evade the host immune response. For instance, Mtb interferes with the overexpression of class II transactivator (CIITA) in macrophages exposed to IFN-γ by inhibiting histone acetylation at its promoter, which can be reverted by the histone deacetylase inhibitor (HDACi) sodium butyrate. In this work, we evaluated whether a different HDACi, valproic acid (VPA), could revert the inhibition of gene expression induced by Mtb...
January 2019: Tuberculosis
Chetan Rathi, Pradeep B Lukka, Santosh Wagh, Richard E Lee, Anne J Lenaerts, Miriam Braunstein, Anthony Hickey, Mercedes Gonzalez-Juarrero, Bernd Meibohm
Spectinamides are a novel series of spectinomycin analogs being developed for the treatment of tuberculosis. Intrapulmonary aerosol (IPA) administration of lead spectinamide 1599 has previously been shown to be more efficacious than subcutaneous (SC) administration at comparable doses. The objective of the current study was to characterize the disposition of 1599 in plasma and lungs in mice in order to provide a potential rationale for the observed efficacy differences. 200 mg/kg of 1599 was administered to healthy BALB/c mice by SC injection or by IPA delivery...
January 2019: Tuberculosis
N Sweetline Anne, B S M Ronald, T M A Senthil Kumar, A Thangavelu
This study was aimed out to explore the presence of drug resistance among M. tuberculosis and M. bovis isolates (n = 51) of bovine origin by conventional broth microdilution method and molecular methods. By broth microdilution method, 16 isolates were found to be resistant to isoniazid, 08 isolates were resistant to pyrazinamide, 09 isolates were resistant to rifampicin and 07 isolates were found to be resistant for ethambutol. Two isolates showed resistance to rifampicin and pyrazinamide, one isolate showed resistance to pyrazinamide and ethambutol and 03 isolates showed resistance to isoniazid and ethambutol...
January 2019: Tuberculosis
João Queirós, Margarita Villar, Angélica Hernández-Jarguín, Vladimir López, Isabel Fernández de Mera, Joaquín Vicente, Paulo C Alves, Christian Gortazar, José de la Fuente
Constraints in the characterization of microbiota community that circulates in the host have limited the extent of co-infection studies in natural populations. In this study, we used a metaproteomics approach to characterize the mandibular lymph nodes microbiota of wild boar (Sus scrofa) naturally exposed to an increasing trend of Mycobacterium tuberculosis complex (MTC) infection. Our results showed a reduction in microbiota diversity and changes in the composition, structure and functionality of the microbiota community associated with an increase in tuberculosis prevalence, from 45% in 2002/06 to 83% in 2009/12...
January 2019: Tuberculosis
Alexander V Dyatlov, Alexander S Apt, Irina A Linge
The role of B cells and antibodies in tuberculosis (TB) immunity, protection and pathogenesis remain contradictory. The presence of organized B cell follicles close to active TB lesions in the lung tissue raises the question about the role of these cells in local host-pathogen interactions. In this short review, we summarize the state of our knowledge concerning phenotypes of B cells populating tuberculous lungs, their secretory activity, interactions with other immune cells and possible involvement in protective vs...
January 2019: Tuberculosis
Krishnaveni Mohareer, Suman Asalla, Sharmistha Banerjee
Tuberculosis (TB) continues to be the leading cause of death by any single infectious agent, accounting for around 1.7 million annual deaths globally, despite several interventions and support programs by national and international agencies. With the development of drug resistance in Mycobacterium tuberculosis (M. tb), there has been a paradigm shift in TB research towards host-directed therapy. The potential targets include the interactions between host and bacterial proteins that are crucial for pathogenesis...
December 2018: Tuberculosis
Anna Solokhina, Gernot Bonkat, Ekatherina Kulchavenya, Olivier Braissant
Biofilms are more resistant to antibiotics and antimicrobial stressors than planktonic bacteria; however, only a limited number of standardized assays enable investigation of this phenomenon. Here, we utilized non-invasive and independent techniques, including isothermal microcalorimetry (IMC) and tunable diode laser absorption spectroscopy (TDLAS), to measure the effect of isoniazid on metabolic activity and respiratory capability of mature Mycobacterium tuberculosis H37Ra (an avirulent strain) and Mycobacterium smegmatis biofilms...
December 2018: Tuberculosis
Pramod Kumar Gupta, Savita Kulkarni
Plethora of clinical and scientific information obtained in recent past has strengthened the idea that targeting critical constituents of host immune system may have beneficial outcomes for the treatment of tuberculosis. Macrophages being the primary host for Mycobacterium tuberculosis, offer an attractive target for modulation. Owing to their negligible toxicity, plant derived polysaccharides with the ability to activate macrophages; are suitable candidates for immunomodulation. In the present study, effects of polysaccharide rich extract (PRE) isolated from Tinospora cordifolia, on the survival of intracellular MTB strains and activation of macrophages were investigated...
December 2018: Tuberculosis
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