Pilot studies of a human BCG challenge model
In this study, five volunteers were challenged with BCG intradermally (ID). Swab specimens were collected at multiple time points from the vaccination site pre- and post-vaccination to quantitate mycobacterial shedding as a surrogate of in vivo mycobacterial immunity. (Source: Tuberculosis)
Source: Tuberculosis - May 4, 2017 Category: Respiratory Medicine Authors: Azra Blazevic, Mei Xia, Aldin Turan, Janice Tennant, Daniel F. Hoft Source Type: research
Quantitative and qualitative iNKT repertoire associations with disease susceptibility and outcome in macaque tuberculosis infection
Correlates of immune protection that reliably predict vaccine efficacy against Mycobacterium tuberculosis (Mtb) infection are urgently needed. Invariant NKT cells (iNKTs) are CD1d-dependent innate T cells that augment host antimicrobial immunity through production of cytokines, including interferon (IFN)- γ and tumour necrosis factor (TNF)-α. We determined peripheral blood iNKT numbers, their proliferative responses and iNKT subset proportions after in vitro antigen expansion by α-galactosylceramide (αGC) in a large cohort of mycobacteria-naïve non-human primates, and macaques from Bacillus Calm ette-Guerin (BCG) vacc...
Source: Tuberculosis - April 28, 2017 Category: Respiratory Medicine Authors: Andrew Chancellor, Andrew White, Anna S. Tocheva, Joe R. Fenn, Mike Dennis, Liku Tezera, Akul Singhania, Tim Elliott, Marc Tebruegge, Paul Elkington, Stephan Gadola, Sally Sharpe, Salah Mansour Source Type: research
The role of the time-kill kinetics assay as part of a preclinical modeling framework for assessing the activity of anti-tuberculosis drugs
Novel treatment strategies for tuberculosis are urgently needed. Many different preclinical models assessing anti-tuberculosis drug activity are available, but it is yet unclear which combination of models is most predictive of clinical treatment efficacy. The aim of this study was to determine the role of our in vitro time kill-kinetics assay as an asset to a predictive preclinical modeling framework assessing anti-tuberculosis drug activity. The concentration- and time-dependent mycobacterial killing capacities of six anti-tuberculosis drugs were determined during exposure as single drugs or in dual, triple and quadruple...
Source: Tuberculosis - April 27, 2017 Category: Respiratory Medicine Authors: Hannelore I. Bax, Irma A.J.M. Bakker-Woudenberg, Corn é P. de Vogel, Aart van der Meijden, Annelies Verbon, Jurriaan E.M. de Steenwinkel Source Type: research
Editorial Board
(Source: Tuberculosis)
Source: Tuberculosis - April 26, 2017 Category: Respiratory Medicine Source Type: research
Evaluation of antigen specific interleukin-1 β as a biomarker to detect cattle infected with Mycobacterium bovis
Bovine tuberculosis (bTB) is a major world-wide health problem that has been difficult to control, due to the lack of an effective vaccine and limited ability of the tuberculin skin test (TST) and the ancillary whole blood interferon-gamma (IFN- γ) release assay (IGRA) to detect all infected animals. A 6 h cytokine flow cytometric IFN-γ (CFC) assay was developed in effort to overcome these limitations and expand methods for studying the mechanisms of bTB immunopathogenesis. The present study was conducted to evaluate IL-1β as a biomarke r to use in conjunction with the IFN-γ CFC assay to improve the diagnostic accurac...
Source: Tuberculosis - April 24, 2017 Category: Respiratory Medicine Authors: Mahmoud M. Elnaggar, Gaber S. Abdellrazeq, Alaa Elsisy, Asmaa H. Mahmoud, Abdelrazeq Shyboub, Martina Sester, Samy A. Khaliel, Mahavir Singh, Helmy A. Torky, William C. Davis Source Type: research
Molecular mechanisms of action, resistance, detection to the first-line anti tuberculosis drugs: Rifampicin and pyrazinamide in the post whole genome sequencing era
Recent studies in addition to studies based on whole genome sequencing (WGS) of clinical isolates of Mycobacterium tuberculosis (MTB) from diverse geographical regions have provided useful insights into the mechanisms of drug resistance. Of importance, are some of the findings pertaining to mechanisms of resistance to two of the first-line anti-tuberculosis (TB) drugs, namely, rifampicin (RIF) and pyrazinamide (PZA). For example, the implication of mutations in rpoA and rpoC genes that act as compensatory mutations for those in the rpoB gene with respect to RIF resistance is noteworthy. (Source: Tuberculosis)
Source: Tuberculosis - April 21, 2017 Category: Respiratory Medicine Authors: Ameeruddin Nusrath Unissa, Luke Elizabeth Hanna Tags: Review Source Type: research
Molecular mechanism of action, resistance, detection to the first-line anti tuberculosis drugs: Rifampicin and pyrazinamide
Recent studies in addition to studies based on whole genome sequencing (WGS) of clinical isolates of Mycobacterium tuberculosis (MTB) from diverse geographical regions have provided useful insights into the mechanisms of drug resistance. Of importance, are some of the findings pertaining to mechanisms of resistance to two of the first-line anti-tuberculosis (TB) drugs, namely, rifampicin (RIF) and pyrazinamide (PZA). For example, the implication of mutations in rpoA and rpoC genes that act as compensatory mutations for those in the rpoB gene with respect to RIF resistance is noteworthy. (Source: Tuberculosis)
Source: Tuberculosis - April 21, 2017 Category: Respiratory Medicine Authors: Ameeruddin Nusrath Unissa, Luke Elizabeth Hanna Tags: Review Source Type: research
SpolSimilaritySearch – A web tool to compare and search similarities between spoligotypes of Mycobacterium tuberculosis complex
Spoligotyping is one of the most commonly used polymerase chain reaction (PCR)-based methods for identification and study of genetic diversity of Mycobacterium tuberculosis complex (MTBC). Despite its known limitations if used alone, the methodology is particularly useful when used in combination with other methods such as mycobacterial interspersed repetitive units – variable number of tandem DNA repeats (MIRU-VNTRs). At a worldwide scale, spoligotyping has allowed identification of information on 103,856 MTBC isolates (corresponding to 98049 clustered strains plus 5807 unique isolates from 169 countries of patient orig...
Source: Tuberculosis - April 20, 2017 Category: Respiratory Medicine Authors: David Couvin, Thierry Zozio, Nalin Rastogi Source Type: research
miR-30c is specifically repressed in patients with active pulmonary tuberculosis
Tuberculous pleurisy (PLTB) is a common form of extrapulmonary tuberculosis. It often resolves without chemotherapy being hence considered a rather benign manifestation of the disease. Patients with PLTB mount an effective anti-mycobacterial response, unlike those with active pulmonary TB (pTB) that were shown to present an imbalance in plasma immune and endocrine mediators. In this work, we explored whether expression of the active isoform of the glucocorticoid receptor (hGR α) in the context of the inflammatory-anti-inflammatory responses of TB patients may be associated to microRNA levels. (Source: Tuberculosis)
Source: Tuberculosis - April 19, 2017 Category: Respiratory Medicine Authors: Silvana V. Spinelli, Roc ío del V. Fernández, Luciana Zoff, Bettina Bongiovanni, Ariana Díaz, Luciano D'Attilio, Natalia Santucci, Tomás Alvarez, Marcela M. Marchesini, Cristina Bogue, Maria L. Bay, Oscar A. Bottasso Source Type: research
A brief history of tuberculosis in the Czech Lands
Tuberculosis currently remains a serious medical problem, therefore increased attention is being paid to this disease. Paleopathological studies focused on the monitoring of morbid changes in skeletal remains of historical populations facilitate a detailed study of the development of this disease. They provide direct evidence of the existence of tuberculosis and its past forms. In addition to literary and iconographic sources, the present study is focused on recording the findings of bone tuberculosis in historical osteological sets from the Czech Lands and is the starting point for their detailed review. (Source: Tuberculosis)
Source: Tuberculosis - April 19, 2017 Category: Respiratory Medicine Authors: Lenka Vargov á, Kateřina Vymazalová, Ladislava Horáčková Tags: Review Source Type: research
miR-30cis specifically repressed in patients with active pulmonary tuberculosis
Tuberculous pleurisy (PLTB) is a common form of extrapulmonary tuberculosis. It often resolves without chemotherapy being hence considered a rather benign manifestation of the disease. Patients with PLTB mount an effective anti-mycobacterial response, unlike those with active pulmonary TB (pTB) that were shown to present an imbalance in plasma immune and endocrine mediators. In this work, we explored whether expression of the active isoform of the glucocorticoid receptor (hGR α) in the context of the inflammatory-anti-inflammatory responses of TB patients may be associated to microRNA levels. (Source: Tuberculosis)
Source: Tuberculosis - April 19, 2017 Category: Respiratory Medicine Authors: Silvana V. Spinelli, Roc ío del V. Fernández, Luciana Zoff, Bettina Bongiovanni, Ariana Díaz, Luciano D'Attilio, Natalia Santucci, Tomás Alvarez, Marcela M. Marchesini, Cristina Bogue, Maria L. Bay, Oscar A. Bottasso Source Type: research
Chemokines additional to IFN- γ can be used to differentiate among Mycobacterium tuberculosis infection possibilities and provide evidence of an early clearance phenotype
Current diagnostic tests for tuberculosis (TB) remain limited in their ability to discriminate between active TB (ATB) and latent TB infection (LTBI). Early clearance (EC) of TB by individuals exposed to Mycobacterium tuberculosis is a debated phenomenon for which evidence is lacking. We measured and compared secreted chemokines in the plasma fraction from 48 ATB, 38 LTBI, 162 presumed EC and 39 healthy controls (HC) using the QuantiFERON ®-TB Gold In-Tube assay. Single chemokine markers were limited in their ability to discriminate between ATB and LTBI: IFN-γ showed 16.7% sensitivity; CCL2 showed moderate sensitivity (7...
Source: Tuberculosis - April 18, 2017 Category: Respiratory Medicine Authors: Ditthawat Nonghanphithak, Wipa Reechaipichitkul, Wises Namwat, Vivek Naranbhai, Kiatichai Faksri Source Type: research
Comparative study of genotypes of Mycobacterium tuberculosis from a Northern Indian setting with strains reported from other parts of India and neighboring countries
This study was carried out to characterize Mycobacterium tuberculosis population in Ghatampur, Kanpur, North India, by spoligotyping and Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTRs) typing. A total of 335 isolates were genotyped by spoligotyping and Central Asian (CAS) sub-lineage was the most prevalent, comprising 59.1% of all isolates. Other lineages were: East-African Indian (EAI) (19.10%), T (5.07%), Beijing (3.28%), Manu (2.98%), X (2.68%), S (0.89%), H3 (0.59%), Ural (0.59%), LAM 9 (0.29%) and unknown (5.37%). (Source: Tuberculosis)
Source: Tuberculosis - April 10, 2017 Category: Respiratory Medicine Authors: Pragya Sharma, Kiran Katoch, Shilpi Chandra, Devendra Singh Chauhan, Vishnu Dutt Sharma, David Couvin, Nalin Rastogi, Vishwa Mohan Katoch Source Type: research
Molecular investigation of active binding site of Isoniazid (INH) and insight into resistance mechanism of S315T-MtKatG in Mycobacterium tuberculosis
Multi drug resistant tuberculosis is a major threat for mankind. Resistance against Isoniazid (INH), targeting MtKatG protein, is one of the most commonly occurring resistances in MDR TB strains. S315T-MtKatG mutation is widely reported for INH resistance. Despite having knowledge about the mechanism of INH, exact binding site of INH to MtKatG is still uncertain and proposed to have three presumable binding sites (site-1, site-2, and site-3). In the current study docking, molecular dynamics simulation, binding free energy estimation, principal component analysis and free energy landscape analysis were performed to get mole...
Source: Tuberculosis - April 10, 2017 Category: Respiratory Medicine Authors: Gaurava Srivastava, Shubhandra Tripathi, Akhil Kumar, Ashok Sharma Source Type: research
Green Fluorescent Protein as a protein localization and topological reporter in mycobacteria
The cell envelope-associated proteins of Mycobacterium species play critical functions in the physiology and pathogenicity of these microorganisms. Because the determination of their subcellular localization and transmembrane topology is often critical to the understanding of their function, we investigated whether the Green Fluorescent Protein (GFP) could be used as a reporter to probe protein localization and map the topology of inner membrane proteins directly in intact mycobacterial cells. To this end, two GFP-based mycobacterial reporter plasmids were engineered and their functionality validated using a variety of mem...
Source: Tuberculosis - April 10, 2017 Category: Respiratory Medicine Authors: Juan Manuel Belardinelli, Mary Jackson Source Type: research
