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Modeling tuberculosis

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https://www.readbyqxmd.com/read/29666166/type-i-interferons-in-tuberculosis-foe-and-occasionally-friend
#1
REVIEW
Lúcia Moreira-Teixeira, Katrin Mayer-Barber, Alan Sher, Anne O'Garra
Tuberculosis remains one of the leading causes of mortality worldwide, and, despite its clinical significance, there are still significant gaps in our understanding of pathogenic and protective mechanisms triggered by Mycobacterium tuberculosis infection. Type I interferons (IFN) regulate a broad family of genes that either stimulate or inhibit immune function, having both host-protective and detrimental effects, and exhibit well-characterized antiviral activity. Transcriptional studies have uncovered a potential deleterious role for type I IFN in active tuberculosis...
April 17, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29665948/preclinical-tools-for-the-evaluation-of-tuberculosis-treatment-regimens-for-children
#2
E W Tucker, K E Dooley
Tuberculosis (TB) treatment regimens have been extrapolated from adults to children. However, pediatric disease merits different treatment strategies to avoid under- or over-treatment. While animal models have been pivotal in identifying effective regimens for adult disease, pediatric TB is heterogeneous and cannot be represented by a single preclinical model. Infants and young children most commonly have disseminated disease or tuberculous meningitis (TBM), school-aged children have paucibacillary disease, and adolescents have adult-like cavitary lung disease...
May 1, 2018: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/29665438/enhancement-of-anti-tubercular-activity-and-biomass-of-fermented-food-associated-staphylococcus-hominis-strain-manf2-using-taguchi-orthogonal-array-and-box-behnken-design
#3
Ameer Khusro, Chirom Aarti, Azger Dusthackeer, Paul Agastian
The prime focus of the present investigation was to optimize statistically the anti-tubercular activity and biomass of fermented food associated Staphylococcus hominis strain MANF2 using Taguchi orthogonal array (OA) and Box-Behnken design (BBD). The anti-tubercular activity of strain MANF2 was determined against Mycobacterium tuberculosis H37Rv using luciferase reporter phase assay. Among varied media examined, the isolate exhibited impressive anti-tubercular activity with paramount relative light unit reduction of >90% in de Man Rogose Sharpe (MRS) broth...
April 14, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29663961/systematic-review-and-meta-analysis-of-adjunctive-corticosteroids-in-the-treatment-of-tuberculous-pericarditis
#4
I A George, B Thomas, J S Sadhu
SETTING: Tuberculosis (TB) is the most common cause of pericarditis worldwide and carries a high mortality, even with effective anti-tuberculosis treatment. In the light of a randomized control trial in 2014, the American Thoracic Society and the Centers for Disease Control and Prevention/Infectious Diseases Society of America recently revised their recommendations against the routine use of adjunctive corticosteroids. OBJECTIVE: To evaluate the strength of evidence that resulted in this reversal of the guideline recommendations on the use of adjunctive corticosteroids in TB pericarditis by a meta-analysis, followed by a sensitivity analysis...
May 1, 2018: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/29663953/cost-effectiveness-of-contact-screening-strategies-for-tuberculosis-among-high-school-adolescents-in-south-korea
#5
H Sohn, H-Y Kim, S H Lee
BACKGROUND: Effective latent tuberculous infection (LTBI) control among adolescents is a critical component of tuberculosis (TB) elimination in Korea. OBJECTIVE: To compare the cost-effectiveness of the following contact screening strategies for LTBI among high-school adolescents after TB outbreaks: QuantiFERON®-TB Gold In-Tube (QFT-GIT), the tuberculin skin test (TST), or TST/QFT-GIT (two-step strategy). METHOD: The costs of post-TB outbreak screening strategies were calculated using a mixed (top-down and bottom-up) cost analysis method and expressed in 2015 US dollars...
May 1, 2018: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/29662482/targeting-mycobacterium-tuberculosis-antigens-to-dendritic-cells-via-the-dc-specific-icam3-grabbing-nonintegrin-receptor-induces-strong-t-helper-1-immune-responses
#6
Lis Noelia Velasquez, Philipp Stüve, Maria Virginia Gentilini, Maxine Swallow, Judith Bartel, Nils Yngve Lycke, Daniel Barkan, Mariana Martina, Hugo D Lujan, Hakan Kalay, Yvette van Kooyk, Tim D Sparwasser, Luciana Berod
Tuberculosis remains a major global health problem and efforts to develop a more effective vaccine have been unsuccessful so far. Targeting antigens (Ags) to dendritic cells (DCs) in vivo has emerged as a new promising vaccine strategy. In this approach, Ags are delivered directly to DCs via antibodies that bind to endocytic cell-surface receptors. Here, we explored DC-specific-ICAM3-grabbing-nonintegrin (DC-SIGN) targeting as a potential vaccine against tuberculosis. For this, we made use of the hSIGN mouse model that expresses human DC-SIGN under the control of the murine CD11c promoter...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29662098/author-correction-sex-differences-in-the-c57bl-6-model-of-mycobacterium-tuberculosis-infection
#7
Jannike Dibbern, Lars Eggers, Bianca E Schneider
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
April 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29661928/identification-and-evaluation-of-novel-protective-antigens-for-the-development-of-a-candidate-tb-subunit-vaccine
#8
Elena Stylianou, Rachel Harrington-Kandt, Julia Beglov, Naomi Bull, Nawamin Pinpathomrat, Gwendolyn M Swarbrick, Deborah A Lewinsohn, David M Lewinsohn, Helen McShane
The development of a vaccine against tuberculosis (TB), a disease caused by Mycobacterium tuberculosis ( M.tb ), is urgently needed. The only currently available vaccine, BCG, has variable efficacy. One approach in the global vaccine development effort is focused on boosting BCG using subunit vaccines. The identification of novel antigens for inclusion in subunit vaccines is a critical step in the TB vaccine development pathway. We selected four novel mycobacterial antigens recognised during the course of human infection...
April 16, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29661879/accelerating-early-anti-tuberculosis-drug-discovery-by-creating-mycobacterial-indicator-strains-that-predict-mode-of-action
#9
Maikel Boot, Susanna Commandeur, Amit K Subudhi, Meriem Bahira, Trever C Smith, Abdallah M Abdallah, Mae van Gemert, Joël Lelièvre, Lluís Ballell, Bree B Aldridge, Arnab Pain, Alexander Speer, Wilbert Bitter
Due to the rise of drug resistant forms of tuberculosis there is an urgent need for novel antibiotics to effectively combat these cases and shorten treatment regimens. Recently, drug screens using whole cell analyses have been shown to be successful. However, current high-throughput screens focus mostly on stricto sensu life-death screening that give little qualitative information. In doing so, promising compound scaffolds or non-optimized compounds that fail to reach inhibitory concentrations are missed. To accelerate early TB drug discovery, we performed RNA sequencing on Mycobacterium tuberculosis and Mycobacterium marinum to map the stress responses that follow upon exposure to sub-inhibitory concentrations of antibiotics with known targets: ciprofloxacin, ethambutol, isoniazid, streptomycin and rifampicin...
April 16, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29661869/moxifloxacin-replacement-in-contemporary-tuberculosis-drug-regimens-is-ineffective-against-persistent-mycobacterium-tuberculosis-novel-insights-from-the-cornell-mouse-model
#10
Yingjun Liu, Henry Pertinez, Geraint R Davies, Stephen H Gillespie, Anthony R Coates, Yanmin Hu
Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a leading killer worldwide, and disease control is hampered by ineffective control of persistent infections. Substitution of moxifloxacin for isoniazid or ethambutol in standard TB regimens reduces treatment duration and relapse rates in animal studies and four-month regimens were not non-inferior in clinical trials. Resuscitation promoting factor (RPF) dependent bacilli have recently been implicated in M. tuberculosis persistence. We aimed to investigate the therapeutic effects of moxifloxacin substitution in the standard drug regimen for eradicating colony forming count (CFU) positive and RPF-dependent persistent M...
April 16, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29661865/modeling-and-simulation-of-pretomanid-pharmacokinetics-in-pulmonary-tuberculosis-patients
#11
Michael A Lyons
Pretomanid is a nitroimidazole antibiotic in late phase clinical testing as a component of several novel antituberculosis (anti-TB) regimens. A population pharmacokinetic model for pretomanid was constructed using a Bayesian analysis of data from two phase 2 studies, PA-824-CL-007 and PA-824-CL-010, conducted with newly diagnosed adult (median age 27 years) pulmonary TB patients in Cape Town, South Africa. Combined, these studies included 63 males and 59 females administered once daily oral pretomanid doses of 50, 100, 150, 200, 600, 1000, or 1200 mg for 14 days...
April 16, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29659820/recent-mouse-models-and-vaccine-candidates-for-preventing-chronic-latent-tuberculosis-infection-and-its-reactivation
#12
César Pedroza-Roldán, Mario Alberto Flores-Valdez
Tuberculosis (TB) remains a major challenge in public health worldwide. Until today, the only widely used and approved vaccine is the Mycobacterium bovis bacille Calmette-Guerin (BCG). This vaccine provides a highly variable level of protection against the active, pulmonary form of tuberculosis, and practically none against the latent form of TB infection. This disparity in protection has been extensively studied, and for this reason, several groups have focused their research on the quest for attenuated vaccines based on M...
August 31, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/29659636/prognostic-score-to-predict-mortality-during-tb-treatment-in-tb-hiv-co-infected-patients
#13
Duc T Nguyen, Helen E Jenkins, Edward A Graviss
BACKGROUND: Estimating mortality risk during TB treatment in HIV co-infected patients is challenging for health professionals, especially in a low TB prevalence population, due to the lack of a standardized prognostic system. The current study aimed to develop and validate a simple mortality prognostic scoring system for TB/HIV co-infected patients. METHODS: Using data from the CDC's Tuberculosis Genotyping Information Management System of TB patients in Texas reported from 01/2010 through 12/2016, age ≥15 years, HIV(+), and outcome being "completed" or "died", we developed and internally validated a mortality prognostic score using multiple logistic regression...
2018: PloS One
https://www.readbyqxmd.com/read/29656849/association-of-highly-active-antiretroviral-treatment-with-incident-tuberculosis-in-people-living-with-hiv-aids
#14
Yung-Feng Yen, I-An Jen, Pei-Hung Chuang, Marcelo Chen, Yu-Ching Lan, Chun-Yuan Lee, Yi-Ming Arthur Chen
PURPOSE: To determine the short-term and long-term effects of highly active antiretroviral therapy (HAART) on incident tuberculosis (TB) in people living with HIV/AIDS (PLWHA). METHODS: From 2000 to 2012, we identified adult PLWHA from Taiwan Centers for Disease Control HIV Surveillance System. All PLWHA were followed up until December 31, 2012, and observed for TB occurrence. Time-dependent Cox proportional hazards models were used to determine the short-term and long-term effects of HAART on incident TB...
March 28, 2018: Annals of Epidemiology
https://www.readbyqxmd.com/read/29652971/-factors-associated-to-survival-in-patients-with-hiv-tb-in-the-department-of-infectious-diseases-of-the-arzobispo-loayza-national-hospital-per%C3%A3%C2%BA-since-2004-to-2012
#15
Brenda Gamboa-Acuña, Rayza Guillén-Zambrano, Grecia Lizzetti-Mendoza, Alonso Soto, Aldo Lucchetti-Rodríguez
Background The main cause of death in HIV patients is tuberculosis (TB). However, few Latin American studies have evaluated the prognosis of patients with coinfection. Aim To determine the factors associated with survival in patients with HIV-TB coinfection treated at a Peruvian referral hospital. Methods A retrospective cohort study was performed based on clinical records of patients treated at the Department of Infectious Diseases in the Arzobispo Loayza National Hospital from 2004 to 2012. Survival was assessed using the Kaplan-Meier estimator and Cox Proportional Hazard Model...
2018: Revista Chilena de Infectología: órgano Oficial de la Sociedad Chilena de Infectología
https://www.readbyqxmd.com/read/29651283/mirnas-in-tuberculosis-new-avenues-for-diagnosis-and-host-directed-therapy
#16
REVIEW
Naveed Sabir, Tariq Hussain, Syed Zahid Ali Shah, Antonio Peramo, Deming Zhao, Xiangmei Zhou
Tuberculosis (TB) is one of the most fatal infectious diseases and a leading cause of mortality, with 95% of these deaths occurring in developing countries. The causative agent, Mycobacterium tuberculosis ( Mtb ), has a well-established ability to circumvent the host's immune system for its intracellular survival. microRNAs (miRNAs) are small, non-coding RNAs having an important function at the post-transcriptional level and are involved in shaping immunity by regulating the repertoire of genes expressed in immune cells...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29650461/towards-designing-a-synthetic-antituberculosis-vaccine-the-rv3587c-peptide-inhibits-mycobacterial-entry-to-host-cells
#17
Mary Lilian Carabali-Isajar, Marisol Ocampo, Deisy Carolina Rodriguez, Magnolia Vanegas, Hernando Curtidor, Manuel Alfonso Patarroyo, Manuel Elkin Patarroyo
Mycobacterium tuberculosis is considered one of the most successful pathogens in the history of mankind, having caused 1.7 million deaths in 2016. The amount of resistant and extensively resistant strains has increased; BCG has been the only vaccine to be produced in more than 100 years though it is still unable to prevent the disease's most disseminated form in adults; pulmonary tuberculosis. The search is thus still on-going for candidate antigens for an antituberculosis vaccine. This paper reports the use of a logical and rational methodology for finding such antigens, this time as peptides derived from the Rv3587c membrane protein...
April 4, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29649520/development-and-validation-of-a-prognostic-score-to-predict-tuberculosis-mortality
#18
Duc T M Nguyen, Edward A Graviss
OBJECTIVE: To develop and validate a simple prognostic scoring system to predict the mortality risk during treatment in tuberculosis patients. METHODS: Using data from the CDC's Tuberculosis Genotyping Information Management System of TB patients in Texas reported from 01/2010 to 12/2016, age ≥ 15 years and having an outcome as "completed" or "died", we developed and validated a prognostic mortality scoring system-based logistic regression beta-coefficients...
April 9, 2018: Journal of Infection
https://www.readbyqxmd.com/read/29649213/new-insights-into-the-transposition-mechanisms-of-is6110-and-its-dynamic-distribution-between-mycobacterium-tuberculosis-complex-lineages
#19
Jesús Gonzalo-Asensio, Irene Pérez, Nacho Aguiló, Santiago Uranga, Ana Picó, Carlos Lampreave, Alberto Cebollada, Isabel Otal, Sofía Samper, Carlos Martín
The insertion Sequence IS6110, only present in the pathogens of the Mycobacterium tuberculosis Complex (MTBC), has been the gold-standard epidemiological marker for TB for more than 25 years, but biological implications of IS6110 transposition during MTBC adaptation to humans remain elusive. By studying 2,236 clinical isolates typed by IS6110-RFLP and covering the MTBC, we remarked a lineage-specific content of IS6110 being higher in modern globally distributed strains. Once observed the IS6110 distribution in the MTBC, we selected representative isolates and found a correlation between the normalized expression of IS6110 and its abundance in MTBC chromosomes...
April 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29642897/small-contribution-of-gold-mines-to-the-ongoing-tuberculosis-epidemic-in-south-africa-a-modeling-based-study
#20
Stewart T Chang, Violet N Chihota, Katherine L Fielding, Alison D Grant, Rein M Houben, Richard G White, Gavin J Churchyard, Philip A Eckhoff, Bradley G Wagner
BACKGROUND: Gold mines represent a potential hotspot for Mycobacterium tuberculosis (Mtb) transmission and may be exacerbating the tuberculosis (TB) epidemic in South Africa. However, the presence of multiple factors complicates estimation of the mining contribution to the TB burden in South Africa. METHODS: We developed two models of TB in South Africa, a static risk model and an individual-based model that accounts for longer-term trends. Both models account for four populations - mine workers, peri-mining residents, labor-sending residents, and other residents of South Africa - including the size and prevalence of latent TB infection, active TB, and HIV of each population and mixing between populations...
April 12, 2018: BMC Medicine
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