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Modeling AND tuberculosis

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https://www.readbyqxmd.com/read/29233902/t-cell-production-of-gm-csf-protects-the-host-during-experimental-tuberculosis
#1
Richard T Robinson
Although classically associated with myelopoiesis, granulocyte-macrophage colony-stimulating factor (GM-CSF) is increasingly recognized as being important for tuberculosis (TB) resistance. GM-CSF is expressed by nonhematopoietic and hematopoietic lineages following infection with Mycobacterium tuberculosis and is necessary to restrict M. tuberculosis growth in experimental models. Until the recent study by Rothchild et al. (mBio 8:e01514-17, 2017, https://doi.org/10.1128/mBio.01514-17), it was unknown whether GM-CSF-producing T cells contribute to TB resistance...
December 12, 2017: MBio
https://www.readbyqxmd.com/read/29233121/do-retreatment-tuberculosis-patients-need-special-treatment-response-follow-up-beyond-the-standard-regimen-finding-of-five-year-retrospective-study-in-pastoralist-setting
#2
Fentabil Getnet, Henok Sileshi, Wubareg Seifu, Selam Yirga, Abere Shiferaw Alemu
BACKGROUND: Treatment outcomes serve as proxy measures of the quality of tuberculosis treatment provided by the health care system, and it is essential to evaluate the effectiveness of Directly Observed Therapy-Short course program in controlling the disease, and reducing treatment failure, default and death. Hence, we evaluated tuberculosis treatment success rate, its trends and predictors of unsuccessful treatment outcome in Ethiopian Somali region where 85% of its population is pastoralist...
December 12, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29233115/development-and-validation-of-college-students-tuberculosis-knowledge-attitudes-and-practices-questionnaire-cs-tbkapq
#3
Hualin Jiang, Shaoru Zhang, Yi Ding, Yuelu Li, Tianhua Zhang, Weiping Liu, Yahui Fan, Yan Li, Rongqiang Zhang, Xuexue Ma
BACKGROUND: China faces many challenges in controlling tuberculosis (TB). One significant challenge is the control of college students' TB. In particular, cross-sectional studies of college students' knowledge, attitudes and practices (KAP) in regard to TB have attracted substantial attention. However, few measurement tools have been developed to aid processes related to expert consultation, pre-testing, reliability and validity testing. Our study developed the College Students' TB Knowledge Attitudes and Practices Questionnaire (CS-TBKAPQ) following the scale development steps...
December 12, 2017: BMC Public Health
https://www.readbyqxmd.com/read/29232366/estimating-the-impact-of-antiretroviral-treatment-on-adult-mortality-trends-in-south-africa-a-mathematical-modelling-study
#4
Leigh F Johnson, Margaret T May, Rob E Dorrington, Morna Cornell, Andrew Boulle, Matthias Egger, Mary-Ann Davies
BACKGROUND: Substantial reductions in adult mortality have been observed in South Africa since the mid-2000s, but there has been no formal evaluation of how much of this decline is attributable to the scale-up of antiretroviral treatment (ART), as previous models have not been calibrated to vital registration data. We developed a deterministic mathematical model to simulate the mortality trends that would have been expected in the absence of ART, and with earlier introduction of ART. METHODS AND FINDINGS: Model estimates of mortality rates in ART patients were obtained from the International Epidemiology Databases to Evaluate AIDS-Southern Africa (IeDEA-SA) collaboration...
December 2017: PLoS Medicine
https://www.readbyqxmd.com/read/29230217/type-i-interferons-in-the-pathogenesis-of-tuberculosis-molecular-drivers-and-immunological-consequences
#5
REVIEW
Meg L Donovan, Thomas E Schultz, Taylor J Duke, Antje Blumenthal
Tuberculosis (TB) remains a major global health threat. Urgent needs in the fight against TB include improved and innovative treatment options for drug-sensitive and -resistant TB as well as reliable biological indicators that discriminate active from latent disease and enable monitoring of treatment success or failure. Prominent interferon (IFN) inducible gene signatures in TB patients and animal models of Mycobacterium tuberculosis infection have drawn significant attention to the roles of type I IFNs in the host response to mycobacterial infections...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29230211/evaluation-of-aggregated-ag85b-antigen-for-its-biophysical-properties-immunogenicity-and-vaccination-potential-in-a-murine-model-of-tuberculosis-infection
#6
Faraz Ahmad, Swaleha Zubair, Pushpa Gupta, Umesh Datta Gupta, Rakesh Patel, Mohammad Owais
Protein aggregates have been reported to act as a reservoir that can release biologically active, native form of precursor protein. Keeping this fact into consideration, it is tempting to exploit protein aggregate-based antigen delivery system as a functional vaccine to expand desirable immunological response in the host. Herein, we explored the capacity of aggregated Ag85B of Mycobacterium tuberculosis (Mtb) to act as a prophylactic vaccine system that releases the precursor antigen in slow and sustained manner...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29229989/necroptotic-signaling-is-primed-in-mycobacterium-tuberculosis-infected-macrophages-but-its-pathophysiological-consequence-in-disease-is-restricted
#7
Michael D Stutz, Samar Ojaimi, Cody Allison, Simon Preston, Philip Arandjelovic, Joanne M Hildebrand, Jarrod J Sandow, Andrew I Webb, John Silke, Warren S Alexander, Marc Pellegrini
Mixed lineage kinase domain-like (MLKL)-dependent necroptosis is thought to be implicated in the death of mycobacteria-infected macrophages, reportedly allowing escape and dissemination of the microorganism. Given the consequent interest in developing inhibitors of necroptosis to treat Mycobacterium tuberculosis (Mtb) infection, we used human pharmacologic and murine genetic models to definitively establish the pathophysiological role of necroptosis in Mtb infection. We observed that Mtb infection of macrophages remodeled the intracellular signaling landscape by upregulating MLKL, TNFR1, and ZBP1, whilst downregulating cIAP1, thereby establishing a strong pro-necroptotic milieu...
December 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29229639/whole-cell-screen-of-fragment-library-identifies-gut-microbiota-metabolite-indole-propionic-acid-as-antitubercular
#8
Dereje A Negatu, Joe J J Liu, Matthew Zimmerman, Firat Kaya, Véronique Dartois, Courtney C Aldrich, Martin Gengenbacher, Thomas Dick
Several key tuberculosis drugs including pyrazinamide, with a molecular weight of 123.1 g/mol, are smaller than the usual drug like molecules. Current drug discovery efforts focus on the screening of larger compounds with molecular weights centered around 400-500 g/mol. Fragment (molecular weight < 300 g/mol) libraries have not been systematically explored for antitubercular activity. Here we screened a collection of 1000 fragments, present in the Maybridge Ro3 library, for whole cell activity against Mycobacterium tuberculosis Twenty-nine primary hits showed dose-dependent growth inhibition equal or better than pyrazinamide...
December 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29228700/association-of-ifngr1-and-ifng-genetic-polymorphisms-with-the-risk-for-pulmonary-tuberculosis-in-the-chinese-tibetan-population
#9
Shumei He, Bo Wang, Xikai Zhu, Zhengshuai Chen, Junyu Chen, Demi Hua, Deji Droma, Wensheng Li, Dongya Yuan, Tianbo Jin
Interferon-gamma (IFNG) and its receptor (IFNGR1) are principal genes that associated with tuberculosis. In the current study we aimed to explore the genetic association of polymorphisms of IFNG and IFNGR1 with the risk of pulmonary tuberculosis (PTB) in the Chinese Tibetan population. We selected 467 PTB patients and 503 healthy controls to genotype 9 single nucleotide polymorphisms (SNPs). The unconditional logistic regression analysis was applied for assessing the associations, and the risk of PTB were evaluated by calculating the odds ratio (OR) and 95% confidence interval (CI)...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29227461/population-pharmacokinetics-of-lopinavir-in-severely-malnourished-hiv-infected-children-and-the-effect-on-treatment-outcomes
#10
Moherndran Archary, Helen Mcllleron, Raziya Bobat, Phillip La Russa, Thobekile Sibaya, Lubbe Wiesner, Stefanie Hennig
BACKGROUND: In developing countries, malnutrition remains a common clinical syndrome at antiretroviral treatment (ART) initiation. Physiological changes due to malnutrition and during nutritional recovery could affect the pharmacokinetics of antiretroviral drugs. METHODS: HIV-infected children admitted with severe acute malnutrition were randomised to early or delayed initiation of lopinavir/ritonavir, abacavir and lamivudine using WHO weight-band dosage charts...
December 8, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/29226732/pharmacokinetics-and-pharmacogenetics-of-anti-tubercular-drugs-a-tool-for-treatment-optimization
#11
Ilaria Motta, Andrea Calcagno, Stefano Bonora
Introduction WHO global strategy is to end tuberculosis epidemic by 2035. Pharmacokinetic and pharmacogenetic studies are increasingly performed and might confirm their potential role in optimizing treatment outcome in specific settings and populations. Insufficient drug exposure seems to be a relevant factor in tuberculosis outcome and for the risk of phenotypic resistance. Areas Covered This review discusses available pharmacokinetic and pharmacogenetic data of first and second-line antitubercular agents in relation to efficacy and toxicity...
December 10, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29226173/long-term-outcome-of-antiretroviral-treatment-in-patients-with-and-without-concomitant-tuberculosis-receiving-health-center-based-care-results-from-a-prospective-cohort-study
#12
Anton Reepalu, Taye Tolera Balcha, Erik Sturegård, Patrik Medstrand, Per Björkman
Background: In order to increase treatment coverage, antiretroviral treatment (ART) is provided through primary health care in low-income high-burden countries, where tuberculosis (TB) co-infection is common. We investigated the long-term outcome of health center-based ART, with regard to concomitant TB. Methods: ART-naïve adults were included in a prospective cohort at Ethiopian health centers and followed for up to 4 years after starting ART. All participants were investigated for active TB at inclusion...
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/29226167/mathematical-modeling-of-chronic-infectious-diseases-unpacking-the-black-box
#13
Anthony T Fojo, Emily A Kendall, Parastu Kasaie, Sourya Shrestha, Thomas A Louis, David W Dowdy
Background: Mathematical models are increasingly used to understand the dynamics of infectious diseases, including "chronic" infections with long generation times. Such models include features that are obscure to most clinicians and decision-makers. Methods: Using a model of a hypothetical active case-finding intervention for tuberculosis in India as an example, we illustrate the effects on model results of different choices for model structure, input parameters, and calibration process...
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/29225476/association-between-the-il-6-gene-polymorphism-and-tuberculosis-risk-a-meta-analysis
#14
REVIEW
Hao Wang, Caishuang Pang, Ni Zeng, Chun Wan, Yongchun Shen, Fuqiang Wen
Background: The gene polymorphism of interleukin-6 (IL-6) has been shown to be implicated in tuberculosis susceptibility in many studies, but with conflicting results. This study aimed to provide more accurate estimation of the relationship between IL-6 gene polymorphism and tuberculosis risk through a meta-analysis. Method: A literature search was performed in PubMed, EMBASE, and other databases. Data were retrieved, and pooled odds ratio (OR) with 95% CI were calculated...
2017: Infection and Drug Resistance
https://www.readbyqxmd.com/read/29225431/insights-from-the-protein-protein-interaction-network-analysis-of-mycobacterium-tuberculosis-toxin-antitoxin-systems
#15
Zoozeal Thakur, Renu Dharra, Vandana Saini, Ajit Kumar, Promod K Mehta
Protein-protein interaction (PPI) network analysis is a powerful strategy to understand M. tuberculosis (Mtb) system level physiology in the identification of hub proteins. In the present study, the PPI network of 79 Mtb toxin-antitoxin (TA) systems comprising of 167 nodes and 234 edges was investigated. The topological properties of PPI network were examined by 'Network analyzer' a cytoscape plugin app and STRING database. The key enriched biological processes and the molecular functions of Mtb TA systems were analyzed by STRING...
2017: Bioinformation
https://www.readbyqxmd.com/read/29223583/the-global-burden-of-tuberculosis-results-from-the-global-burden-of-disease-study-2015
#16
(no author information available yet)
BACKGROUND: An understanding of the trends in tuberculosis incidence, prevalence, and mortality is crucial to tracking of the success of tuberculosis control programmes and identification of remaining challenges. We assessed trends in the fatal and non-fatal burden of tuberculosis over the past 25 years for 195 countries and territories. METHODS: We analysed 10 691 site-years of vital registration data, 768 site-years of verbal autopsy data, and 361 site-years of mortality surveillance data using the Cause of Death Ensemble model to estimate tuberculosis mortality rates...
December 6, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/29219122/towards-the-use-of-breath-for-detecting-mycobacterial-infection-a-case-study-in-a-murine-model
#17
Flavio Antonio Franchina, Theodore Robert Mellors, Minara Aliyeva, Jeffrey Wagner, Nirav Daphtary, Lennart Lundblad, Sarah M Fortune, Eric J Rubin, Jane E Hill
In the present research, the potential of breath analysis by comprehensive two-dimensional gas chromatography coupled to mass spectrometry (GC×GC-MS) was investigated for the discrimination between healthy and infected mice. A pilot study employing a total of 16 animals was used to develop a method for breath analysis in a murine model for studying MTBC (Mycobacterium tuberculosis complex) using the M. bovis BCG (Bacillus Calmette-Guérin). Breath was collected in Tedlar bags and concentrated onto thermal desorption tubes for the subsequent analysis by GC×GC-MS...
December 8, 2017: Journal of Breath Research
https://www.readbyqxmd.com/read/29218640/oxoiron-iv-complexes-as-synthons-for-the-assembly-of-heterobimetallic-centers-such-as-the-fe-mn-active-site-of-class-ic-ribonucleotide-reductases
#18
Ang Zhou, Patrick M Crossland, Apparao Draksharapu, Andrew J Jasniewski, Scott T Kleespies, Lawrence Que
Nonheme oxoiron(IV) complexes can serve as synthons for generating heterobimetallic oxo-bridged dimetal complexes by reaction with divalent metal complexes. The formation of FeIII-O-CrIII and FeIII-O-MnIII complexes is described herein. The latter complexes may serve as models for the FeIII-X-MnIII active sites of an emerging class of Fe/Mn enzymes represented by the Class 1c ribonucleotide reductase from Chlamydia trachomatis and the R2-like ligand-binding oxidase (R2lox) found in Mycobacterium tuberculosis...
December 7, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/29216851/what-does-igra-testing-add-to-the-diagnosis-of-ocular-tuberculosis-a-bayesian-latent-class-analysis
#19
Rupesh Agrawal, Robert Grant, Bhaskar Gupta, Dinesh Visva Gunasekeran, Julio J Gonzalez-Lopez, Peter K F Addison, Mark Westcott, Carlos E Pavesio
BACKGROUND: To evaluate the contribution made to the diagnostic work-up for patients with suspected ocular tuberculosis (TB) by QuantiFERON-TB Gold In-Tube (QFT) tests using latent class analysis model. METHODS: A single centre retrospective cohort study. A Bayesian latent class model was constructed on the basis of demographics, phenotypes and test results from patients attending a tertiary referral center in the UK. This estimated the probability of ocular TB for each patient in two versions, first with and then without QFT...
December 8, 2017: BMC Ophthalmology
https://www.readbyqxmd.com/read/29216510/evolution-of-virulence-in-the-mycobacterium-tuberculosis-complex
#20
REVIEW
Mickael Orgeur, Roland Brosch
Mycobacterium tuberculosis, the causative agent of human tuberculosis is one of the most widely spread human pathogens. It has succeeded to infect a quarter of the global human population by developing most sophisticated ways to circumvent innate and adaptive immune defences. This highly specialized, major human pathogen has evolved from a pool of ancestral environmental mycobacteria, whose extant representatives are known under the name of Mycobacterium canettii. Recent whole genome analyses in combination with different phenotypic screens have provided key insights into the evolution of M...
December 4, 2017: Current Opinion in Microbiology
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