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Modeling tuberculosis

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https://www.readbyqxmd.com/read/28097645/bacterial-subversion-of-camp-signalling-inhibits-cathelicidin-expression-which-is-required-for-innate-resistance-to-mycobacterium-tuberculosis
#1
Shashank Gupta, Kathryn Winglee, Richard Gallo, William R Bishai
Antimicrobial peptides such as cathelicidins are an important component of innate immune defence against inhaled microorganisms and have demonstrated antimicrobial activity against Mycobacterium tuberculosis with in vitro models. Despite this, little is known about the regulation and expression of cathelicidin during tuberculosis in vivo. We sought to determine whether the cathelicidin-related antimicrobial peptide (Cramp) gene, the murine functional homologue of the human cathelicidin gene (CAMP or LL-37), is required for regulating protective immunity during M...
January 18, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28096490/comprehensive-essentiality-analysis-of-the-mycobacterium-tuberculosis-genome-via-saturating-transposon-mutagenesis
#2
Michael A DeJesus, Elias R Gerrick, Weizhen Xu, Sae Woong Park, Jarukit E Long, Cara C Boutte, Eric J Rubin, Dirk Schnappinger, Sabine Ehrt, Sarah M Fortune, Christopher M Sassetti, Thomas R Ioerger
: For decades, identifying the regions of a bacterial chromosome that are necessary for viability has relied on mapping integration sites in libraries of random transposon mutants to find loci that are unable to sustain insertion. To date, these studies have analyzed subsaturated libraries, necessitating the application of statistical methods to estimate the likelihood that a gap in transposon coverage is the result of biological selection and not the stochasticity of insertion. As a result, the essentiality of many genomic features, particularly small ones, could not be reliably assessed...
January 17, 2017: MBio
https://www.readbyqxmd.com/read/28093078/treatment-outcomes-for-multidrug-resistant-tuberculosis-under-dots-plus-a-systematic-review-and-meta-analysis-of-published-studies
#3
Kelemu Tilahun Kibret, Yonatan Moges, Peter Memiah, Sibhatu Biadgilign
BACKGROUND: Anti-tuberculosis drug resistance is a major public health problem that threatens the progress made in tuberculosis care and control worldwide. Treatment success rates of multidrug-resistant tuberculosis (MDR-TB) is a key issue that cannot be ignored. There is a paucity of evidence that assessed studies on the treatment of MDR-TB, which focus on the effectiveness of the directly observed treatment, short-course (DOTS)-Plus program. Therefore, it is crucial to assess and summarize the overall treatment outcomes for MDR-TB patients enrolled in the DOTS-Plus program in recent years...
January 17, 2017: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/28092959/mixed-vaccination-strategy-for-the-control-of-tuberculosis-a-case-study-in-china
#4
Siyu Liu, Yong Li, Yingjie Bi, Qingdao Huang
This study first presents a mathematical model of TB transmission considering BCG vaccination compartment to investigate the transmission dynamics nowadays. Based on data reported by the National Bureau of Statistics of China, the basic reproduction number is estimated approximately as R0=1.1892. To reach the new End TB goal raised by WHO in 2015, considering the health system in China, we design a mixed vaccination strategy. Theoretical analysis indicates that the infectious population asymptotically tends to zero with the new vaccination strategy which is the combination of constant vaccination and pulse vaccination...
June 1, 2017: Mathematical Biosciences and Engineering: MBE
https://www.readbyqxmd.com/read/28091336/who-are-the-patients-that-default-tuberculosis-treatment-space-matters
#5
C Nunes, R Duarte, A M Veiga, B Taylor
The goals of this article are: (i) to understand how individual characteristics affect the likelihood of patients defaulting their pulmonary tuberculosis (PTB) treatment regimens; (ii) to quantify the predictive capacity of these risk factors; and (iii) to quantify and map spatial variation in the risk of defaulting. We used logistic regression models and generalized additive models with a spatial component to determine the odds of default across continental Portugal. We focused on new PTB cases, diagnosed between 2000 and 2013, and included some individual information (sex, age, residence area, alcohol abuse, intravenous drug use, homelessness, HIV, imprisonment status)...
January 16, 2017: Epidemiology and Infection
https://www.readbyqxmd.com/read/28088237/association-between-diabetes-mellitus-and-multi-drug-resistant-tuberculosis-a-protocol-for-a-systematic-review-and-meta-analysis
#6
Balewgizie Sileshi Tegegne, Tesfa Dejenie Habtewold, Melkamu Merid Mengesha, Johannes G M Burgerhof
INTRODUCTION: Multi-drug-resistant tuberculosis (MDR-TB) has emerged as a challenge to global tuberculosis (TB) control and remains a major public health concern in many countries. Diabetes mellitus (DM) is an increasingly recognized comorbidity that can both accelerate TB disease and complicate its treatment. The aim of this study is to summarize available evidence on the association of DM and MDR-TB among TB patients and to provide a pooled estimate of risks. METHODS: All studies published in English before October 2016 will be searched using comprehensive search strings through PubMed, EMBASE, Web of Science, and WHO Global Health Library databases which have reported the association of DM and MDR-TB in adults with TB (age > =15)...
January 14, 2017: Systematic Reviews
https://www.readbyqxmd.com/read/28087948/regulation-of-immunity-to-tuberculosis
#7
Susanna Brighenti, Diane J Ordway
Immunity against Mycobacterium tuberculosis requires a balance between adaptive immune responses to constrain bacterial replication and the prevention of potentially damaging immune activation. Regulatory T (Treg) cells express the transcription factor Foxp3+ and constitute an essential counterbalance of inflammatory Th1 responses and are required to maintain immune homeostasis. The first reports describing the presence of Foxp3-expressing CD4+ Treg cells in tuberculosis (TB) emerged in 2006. Different Treg cell subsets, most likely specialized for different tissues and microenvironments, have been shown to expand in both human TB and animal models of TB...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087940/the-memory-immune-response-to-tuberculosis
#8
Joanna R Kirman, Marcela I Henao-Tamayo, Else Marie Agger
Immunological memory is a central feature of the adaptive immune system and a prerequisite for generating effective vaccines. Understanding long-term memory responses to Mycobacterium tuberculosis will thus provide us with valuable insights that can guide us in the search for a novel vaccine against tuberculosis (TB). For many years, triggering CD4 T cells and, in particular, those secreting interferon-γ has been the goal of most TB vaccine research, and numerous data from animals and humans support the key role of this subset in protective immunity...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087924/clinical-testing-of-tuberculosis-vaccine-candidates
#9
Mark Hatherill, Dereck Tait, Helen McShane
It is almost 100 years since the development of bacille Calmette-Guérin (BCG), the only licensed vaccine against tuberculosis (TB). While BCG does confer consistent protection against disseminated disease, there is an urgent need for a more effective vaccine against pulmonary disease. There are several indications for such an improved vaccine, including prevention of infection, prevention of disease, and a therapeutic vaccine to prevent recurrent disease. The two main approaches to TB vaccine development are developing an improved whole mycobacterial priming agent to replace BCG and/or developing a subunit booster vaccine to be administered after a BCG or BCG replacement priming vaccination...
October 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087528/engineering-mycobacteria-for-the-production-of-self-assembling-biopolyesters-displaying-mycobacterial-antigens-for-use-as-tuberculosis-vaccine
#10
Jason W Lee, Natalie A Parlane, Bernd H A Rehm, Bryce M Buddle, Axel Heiser
: Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis or Mycobacterium bovis and still remains one of the world's biggest global health burdens. Recently, engineered polyhydroxyalkanoate (PHA) biobeads produced in both E. coli and Lactococcus lactis displaying mycobacterial antigens were found to induce significant cell mediated immune responses in mice. We observed that such PHA beads contained host cell proteins as impurities which we hypothesized to have the potential to induce immunity...
January 13, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28086846/stochastic-agent-based-modeling-of-tuberculosis-in-canadian-indigenous-communities
#11
Ashleigh R Tuite, Victor Gallant, Elaine Randell, Annie-Claude Bourgeois, Amy L Greer
BACKGROUND: In Canada, active tuberculosis (TB) disease rates remain disproportionately higher among the Indigenous population, especially among the Inuit in the north. We used mathematical modeling to evaluate how interventions might enhance existing TB control efforts in a region of Nunavut. METHODS: We developed a stochastic, agent-based model of TB transmission that captured the unique household and community structure. Evaluated interventions included: (i) rapid treatment of active cases; (ii) rapid contact tracing; (iii) expanded screening programs for latent TB infection (LTBI); and (iv) reduced household density...
January 13, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28078341/the-role-of-uv-radiation-and-vitamin-d-in-the-seasonality-and-outcomes-of-infectious-disease
#12
Abhimanyu, Anna K Coussens
The seasonality of infectious disease outbreaks suggests that environmental conditions have a significant effect on disease risk. One of the major environmental factors that can affect this is solar radiation, primarily acting through ultraviolet radiation (UVR), and its subsequent control of vitamin D production. Here we show how UVR and vitamin D, which are modified by latitude and season, can affect host and pathogen fitness and relate them to the outcomes of bacterial, viral and vector-borne infections...
January 12, 2017: Photochemical & Photobiological Sciences
https://www.readbyqxmd.com/read/28077441/predicting-ifn-%C3%AE-responses-after-bcg-vaccination-in-humans-from-macaques-a-proof-of-concept-study-of-immunostimulation-immunodynamic-modelling-methods
#13
Sophie J Rhodes, Charlotte Sarfas, Gwenan M Knight, Andrew White, Ansar A Pathan, Helen McShane, Thomas G Evans, Helen Fletcher, Sally Sharpe, Richard G White
INTRODUCTION: Macaques play a central role in human tuberculosis(TB) vaccine development. Immune and challenge responses differ across macaque and human subpopulations. We determined which macaque subpopulations best predicted immune responses in different human subpopulations, using novel immunostimulation/immunodynamic modelling methods in a proof of concept study. METHODS: Data on IFN-γ secreting CD4+ T cells over time after recent BCG vaccination were available for 55 humans and 81 macaques...
January 11, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28075556/biosynthesis-of-the-methylthioxylose-capping-motif-of-lipoarabinomannan-in-mycobacterium-tuberculosis
#14
Shiva Kumar Angala, Michael R McNeil, Libin Shi, Maju Joe, Ha Pham, Sophie Zuberogoitia, Jerome Nigou, Claudia M Boot, Todd L Lowary, Martine Gilleron, Mary Jackson
Lipoarabinomannan (LAM) is a lipoglycan found in abundant quantities in the cell envelope of all mycobacteria. The non-reducing arabinan termini of LAM display species-specific structural micro-heterogeneity that impacts the biological activity of the entire molecule. Mycobacterium tuberculosis, for instance, produces mannoside caps made of one to three α(1→2)-Manp-linked residues that may be further substituted with an α(1→4)-linked methylthio-D-xylose (MTX) residue. While the biological functions and catalytic steps leading to the formation of the mannoside caps of M...
January 11, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28075132/discovery-of-imidazo-1-2-a-pyridine-ethers-and-squaramides-as-selective-and-potent-inhibitors-of-mycobacterial-adenosine-triphosphate-atp-synthesis
#15
Subramanyam J Tantry, Shankar D Markad, Vikas Shinde, Jyothi Bhat, Gayathri Balakrishnan, Amit K Gupta, Anisha Ambady, Anandkumar V Raichurkar, Chaitanyakumar Kedari, Sreevalli Sharma, Naina V Mudugal, Ashwini Narayan, C N Naveen Kumar, Robert Nanduri, Sowmya Bharath, Jitendar Reddy, Vijender Panduga, Prabhakar K R, Karthikeyan Kandaswamy, Ramanatha Saralaya, Parvinder Kaur, Neela Dinesh, Supreeth Guptha, Kirsty Rich, David Murray, Helen Plant, Marian Preston, Helen Ashton, Darren Plant, Jarrod Walsh, Peter Alcock, Kathryn Naylor, Matthew Collier, James Whiteaker, Robert E McLaughlin, Meenakshi Mallya, Manoranjan Panda, Suresh Rudrapatna, Vasanthi Ramachandran, Radha K Shandil, Vasan K Sambandamurthy, Khisimuzi Mdluli, Christopher B Cooper, Harvey Rubin, Takahiro Yano, Pravin S Iyer, Shridhar Narayanan, Stefan Kavanagh, Kakoli Mukherjee, V Balasubramanian, Vinayak P Hosagrahara, Suresh Solapure, Sudha Ravishankar, Shahul Hameed P
The approval of bedaquiline to treat tuberculosis has validated adenosine triphosphate (ATP) synthase as an attractive target to kill Mycobacterium tuberculosis. Herein, we report the discovery of two diverse lead series imidazo[1,2-a]pyridine ethers (IPE) and squaramides (SQA) as inhibitors of mycobacterial ATP-synthesis. Through medicinal chemistry exploration, we established a robust structure activity relationship of these two scaffolds resulting in nanomolar potencies in an ATP-synthesis inhibition assay...
January 11, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28070534/design-and-construction-of-a-cloning-vector-containing-the-hspx-gene-of-mycobacterium-tuberculosis
#16
Yaghoubi Atieh, Aryan Ehsan, Zare Hosna, Alami Shadi, Teimourpour Roghayeh, Meshkat Zahra
BACKGROUND: Tuberculosis (TB) is a major cause of death worldwide. Finding an effective vaccine against TB is the best way to control it. Several vaccines against this disease have been developed but none are completely protective. The aim of this study was to design and construct a cloning vector containing the Mycobacterium tuberculosis (M. tuberculosis) heat shock protein X (hspX). METHODS: First, an hspX fragment was amplified by PCR and cloned into plasmid pcDNA3...
October 2016: Reports of Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/28068907/hospitalized-care-for-mdr-tb-in-port-harcourt-nigeria-a-qualitative-study
#17
Kingsley Lezor Bieh, Ralf Weigel, Helen Smith
BACKGROUND: In Nigeria multidrug-resistant tuberculosis (MDR-TB) is prevalent in 2.9% of new TB cases and 14% of retreatment cases, and the country is one of 27 with high disease burden globally. Patients are admitted and confined to one of ten MDR-TB treatment facilities throughout the initial 8 months of treatment. The perspectives of MDR-TB patients shared on social media and in academic research and those of providers are limited to experiences of home-based care. In this study we explored the views of hospitalised MDR-TB patients and providers in one treatment facility in Nigeria, and describe how their experiences are linked to accessibility of care and support services, in line with international goals...
January 10, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28066854/live-donor-liver-transplantation-for-antitubercular-drug-induced-acute-liver-failure
#18
Akshay P Bavikatte, S Sudhindran, Puneet Dhar, O V Sudheer, G Unnikrishnan, Dinesh Balakrishnan, Ramachandran N Menon
Antitubercular therapy (ATT)-induced hepatotoxicity is often over looked and active tuberculosis is considered a contraindication for liver transplantation, however it might be the only lifesaving option to certain patients of acute liver failure (ALF) due to ATT. We have assessed the outcome of live donor liver transplantation in ATT-induced ALF. A retrospective analysis of all the cases of ALF that underwent liver transplantation from 2006 to 2014 at the Amrita Institute of Medical Sciences was done. A total of seven (7...
January 9, 2017: Indian Journal of Gastroenterology: Official Journal of the Indian Society of Gastroenterology
https://www.readbyqxmd.com/read/28065665/unbiased-identification-of-blood-based-biomarkers-for-pulmonary-tuberculosis-by-modeling-and-mining-molecular-interaction-networks
#19
Awanti Sambarey, Abhinandan Devaprasad, Abhilash Mohan, Asma Ahmed, Soumya Nayak, Soumya Swaminathan, George D'Souza, Anto Jesuraj, Chirag Dhar, Subash Babu, Annapurna Vyakarnam, Nagasuma Chandra
Efficient diagnosis of tuberculosis (TB) is met with multiple challenges, calling for a shift of focus from pathogen-centric diagnostics towards identification of host-based multi-marker signatures. Transcriptomics offer a list of differentially expressed genes, but cannot by itself identify the most influential contributors to the disease phenotype. Here, we describe a computational pipeline that adopts an unbiased approach to identify a biomarker signature. Data from RNA sequencing from whole blood samples of TB patients were integrated with a curated genome-wide molecular interaction network, from which we obtain a comprehensive perspective of variations that occur in the host due to TB...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28065210/prevalence-of-tuberculosis-infection-in-healthcare-workers-of-the-public-hospital-network-in-medell%C3%A3-n-colombia-a-bayesian-approach
#20
J Ochoa, A L León, I C Ramírez, C M Lopera, E Bernal, M P Arbeláez
A latent tuberculosis infection (LTBI) prevalence survey was conducted using tuberculin skin test (TST) and Quantiferon test (QFT) in 1218 healthcare workers (HCWs) in Medellín, Colombia. In order to improve the prevalence estimates, a latent class model was built using a Bayesian approach with informative priors on the sensitivity and specificity of the TST. The proportion of concordant results (TST+,QFT+) was 41% and the discordant results contributed 27%. The marginal estimate of the prevalence P(LTBI+) was 62·1% [95% credible interval (CrI) 53·0-68·2]...
January 9, 2017: Epidemiology and Infection
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