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Modeling tuberculosis

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https://www.readbyqxmd.com/read/28823010/the-reliability-of-rifampicin-resistance-as-a-proxy-for-multidrug-resistant-tuberculosis-a-systematic-review-of-studies-from-iran
#1
REVIEW
M J Nasiri, S Zamani, A Pormohammad, M M Feizabadi, H R Aslani, M Amin, R Halabian, A A Imani Fooladi
In Iran, patients showing rifampicin (RIF) resistance detected by the Xpert® MTB/RIF assay are considered as candidates for multidrug-resistant tuberculosis (MDR-TB) treatment. Despite the fact that RIF resistance has been used as a proxy for MDR-TB, little is known about the proportion of isoniazid (INH) resistance patterns in RIF-resistant TB. We systematically searched MEDLINE, Embase, and other databases up to March 2017 for studies addressing the proportion of INH resistance patterns in RIF-resistant TB in Iran...
August 19, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28821621/protein-kinase-g-confers-survival-advantage-to-mycobacterium-tuberculosis-during-latency-like-conditions
#2
Mehak Zahoor Khan, Ashima Bhaskar, Sandeep Upadhyay, Pooja Kumari, Raju S Rajmani, Preeti Jain, Amit Singh, Dhiraj Kumar, Neel Sarovar Bhavesh, Vinay Kumar Nandicoori
Protein Kinase G (PknG), a thioredoxin-fold containing eukaryotic like serine/threonine protein kinase (STPK), is a virulence factor in the Mycobacterium tuberculosis, required for inhibition of phago-lysosomal fusion. Here, we unravelled novel functional facets of PknG during latency like conditions. We find that PknG mediates persistence under stressful conditions like hypoxia and abets drug tolerance. PknG mutant displayed minimal growth in nutrient limiting conditions suggesting its role in modulating cellular metabolism...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821264/impact-of-early-initiation-versus-national-standard-of-care-of-antiretroviral-therapy-in-swaziland-s-public-sector-health-system-study-protocol-for-a-stepped-wedge-randomized-trial
#3
Fiona J Walsh, Till Bärnighausen, Wim Delva, Yvette Fleming, Gavin Khumalo, Charlotte L Lejeune, Sikhathele Mazibuko, Charmaine Khudzie Mlambo, Ria Reis, Donna Spiegelman, Mandisa Zwane, Velephi Okello
BACKGROUND: There is robust clinical evidence to support offering early access to antiretroviral treatment (ART) to all HIV-positive individuals, irrespective of disease stage, to both improve patient health outcomes and reduce HIV incidence. However, as the global treatment guidelines shift to meet this evidence, it is still largely unknown if early access to ART for all (also referred to as "treatment as prevention" or "universal test and treat") is a feasible intervention in the resource-limited countries where this approach could have the biggest impact on the course of the HIV epidemics...
August 18, 2017: Trials
https://www.readbyqxmd.com/read/28820678/a-new-hybrid-model-using-an-autoregressive-integrated-moving-average-and-a-generalized-regression-neural-network-for-the-incidence-of-tuberculosis-in-heng-county-china
#4
Wudi Wei, Junjun Jiang, Lian Gao, Bingyu Liang, Jiegang Huang, Ning Zang, Chuanyi Ning, Yanyan Liao, Jingzhen Lai, Jun Yu, Fengxiang Qin, Hui Chen, Jinming Su, Li Ye, Hao Liang
It is a daunting task to eradicate tuberculosis completely in Heng County due to a large transient population, human immunodeficiency virus/tuberculosis coinfection, and latent infection. Thus, a high-precision forecasting model can be used for the prevention and control of tuberculosis. In this study, four models including a basic autoregressive integrated moving average (ARIMA) model, a traditional ARIMA-generalized regression neural network (GRNN) model, a basic GRNN model, and a new ARIMA-GRNN hybrid model were used to fit and predict the incidence of tuberculosis...
July 31, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28817682/experimental-study-of-tuberculosis-from-animal-models-to-complex-cell-systems-and-organoids
#5
REVIEW
Kaori L Fonseca, Pedro N S Rodrigues, I Anna S Olsson, Margarida Saraiva
Tuberculosis (TB) is a devastating disease to mankind that has killed more people than any other infectious disease. Despite many efforts and successes from the scientific and health communities, the prospect of TB elimination remains distant. On the one hand, sustainable public health programs with affordable and broad implementation of anti-TB measures are needed. On the other hand, achieving TB elimination requires critical advances in three areas: vaccination, diagnosis, and treatment. It is also well accepted that succeeding in advancing these areas requires a deeper knowledge of host-pathogen interactions during infection, and for that, better experimental models are needed...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28817561/comparing-efficacies-of-moxifloxacin-levofloxacin-and-gatifloxacin-in-tuberculosis-granulomas-using-a-multi-scale-systems-pharmacology-approach
#6
Elsje Pienaar, Jansy Sarathy, Brendan Prideaux, Jillian Dietzold, Véronique Dartois, Denise E Kirschner, Jennifer J Linderman
Granulomas are complex lung lesions that are the hallmark of tuberculosis (TB). Understanding antibiotic dynamics within lung granulomas will be vital to improving and shortening the long course of TB treatment. Three fluoroquinolones (FQs) are commonly prescribed as part of multi-drug resistant TB therapy: moxifloxacin (MXF), levofloxacin (LVX) or gatifloxacin (GFX). To date, insufficient data are available to support selection of one FQ over another, or to show that these drugs are clinically equivalent. To predict the efficacy of MXF, LVX and GFX at a single granuloma level, we integrate computational modeling with experimental datasets into a single mechanistic framework, GranSim...
August 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28814276/treatment-outcomes-of-patients-with-multidrug-resistant-and-extensively-drug-resistant-tuberculosis-in-hunan-province-china
#7
Kefyalew Addis Alene, Hengzhong Yi, Kerri Viney, Emma S McBryde, Kunyun Yang, Liqiong Bai, Darren J Gray, Archie C A Clements, Zuhui Xu
BACKGROUND: The worldwide emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) has posed additional challenges for global tuberculosis (TB) control efforts, as limited treatment options are available and treatment outcomes are often sub-optimal. This study determined treatment outcomes among a cohort of MDR-TB and XDR-TB patients in Hunan Province, China, and identified factors associated with poor treatment outcomes. METHODS: We conducted a retrospective study using data obtained from medical records of TB patients in Hunan Chest Hospital, and from the internet-based TB management information system managed by the Tuberculosis Control Institute of Hunan Province, for the period 2011 to 2014...
August 16, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28811474/the-mycobacterial-phosphatase-ptpa-regulates-the-expression-of-host-genes-and-promotes-cell-proliferation
#8
Jing Wang, Pupu Ge, Lihua Qiang, Feng Tian, Dongdong Zhao, Qiyao Chai, Mingzhao Zhu, Rongbin Zhou, Guangxun Meng, Yoichiro Iwakura, George Fu Gao, Cui Hua Liu
Mycobacterium tuberculosis PtpA is a secreted effector protein that dephosphorylates several proteins in the host cell cytoplasm, such as p-JNK, p-p38, and p-VPS33B, leading to suppression of host innate immunity. Here we show that, in addition, PtpA enters the nucleus of host cells and regulates the expression of host genes, some of which are known to be involved in host innate immunity or in cell proliferation and migration (such as GADD45A). PtpA can bind directly to the promoter region of GADD45A in vitro...
August 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28810840/the-association-between-tuberculosis-and-the-development-of-insulin-resistance-in-adults-with-pulmonary-tuberculosis-in-the-western-sub-district-of-the-cape-metropole-region-south-africa-a-combined-cross-sectional-cohort-study
#9
Lauren Philips, Janicke Visser, Daan Nel, Renée Blaauw
BACKGROUND: The existence of a bi-directional relationship between tuberculosis (TB) and insulin resistance (IR)/diabetes has been alluded to in literature. Although diabetes has been linked to increased tuberculosis risk, the relationship between tuberculosis as a causative factor for IR remains unclear. The study aimed to determine if an association existed between tuberculosis and IR development in adults with newly diagnosed pulmonary tuberculosis at baseline. It was additionally aimed to document changes in IR status during TB follow-up periods...
August 15, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28809501/microencapsulated-solid-lipid-nanoparticles-as-a-hybrid-platform-for-pulmonary-antibiotic-delivery
#10
Diana P Gaspar, Maria Manuela Gaspar, Carla V Eleutério, Ana Grenha, Mateo Blanco, Lídia M D Gonçalves, Pablo Taboada, António J Almeida, Carmen Remuñán-López
Solid lipid nanoparticles (SLN) containing rifabutin (RFB), with pulmonary administration purposes, were developed through a technique that avoids the use of organic solvents or sonication. To facilitate their pulmonary delivery, the RFB-loaded SLN were included in microspheres of appropriate size using suitable excipients (mannitol and trehalose) through a spray-drying technique. Confocal analysis microscopy showed that microspheres are spherical and that SLN are efficiently microencapsulated and homogeneously distributed throughout the microsphere matrices...
August 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28808382/allium-sativum-constituents-exhibit-anti-tubercular-activity-in-vitro-and-in-raw-264-7-mouse-macrophage-cells-infected-with-mycobacterium-tuberculosis-h37rv
#11
Swapna S Nair, Sujay S Gaikwad, Savita P Kulkarni, Alka Pravin Mukne
BACKGROUND: Long duration of treatment, side-effects of currently used anti-tubercular drugs and emergence of drug-resistant forms of Mycobacterium tuberculosis (MTB) warrants the need to develop new drugs to tackle the scourge of tuberculosis (TB). Garlic is an edible plant reported to have anti-tubercular activity. However, previous researches on anti-tubercular effect of garlic were focused mostly on preliminary in vitro screening. OBJECTIVE: To identify constituents responsible for anti-tubercular activity of thiosulfinate-derivative rich extract of garlic (GE) and to evaluate activity of the most active constituent in RAW 264...
July 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28807917/bedaquiline-inhibits-the-atp-synthase-in-mycobacterium-abscessus-and-is-effective-in-infected-zebrafish
#12
Christian Dupont, Albertus Viljoen, Sangeeta Thomas, Françoise Roquet-Banères, Jean-Louis Herrmann, Kevin Pethe, Laurent Kremer
Pulmonary infections caused by Mycobacterium abscessus are emerging as a global threat, especially in cystic fibrosis patients. Further intensifying the concern of M. abscessus infection is the recent evidence of human-to-human transmission of the infection. M. abscessus is a naturally multidrug resistant, fast-growing pathogen for which pharmacological options are limited. Repurposing antitubercular drugs represents an attractive option for the development of chemotherapeutic alternatives against M. abscessus infections...
August 14, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28807911/systematic-review-and-meta-analyses-of-the-effect-of-chemotherapy-on-pulmonary-mycobacterium-abscessus-outcomes-and-disease-recurrence
#13
Jotam G Pasipanodya, Deborah Ogbonna, Beatriz E Ferro, Gesham Magombedze, Shashikant Srivastava, Devyani Deshpande, Tawanda Gumbo
Background. In pharmacokinetic/pharmacodynamics models of pulmonary Mycobacterium abscessus complex, the recommended macrolide-containing combination therapy has poor kill rates. However, clinical outcomes are unknown.Methods We searched the literature for studies published between 1990-2017 that reported microbial outcomes in patients treated for pulmonary M. abscessus disease. Good outcome was defined as sustained sputum culture conversion (SSCC) without relapse. Random effects models were used to pool studies and estimate proportions of patients with good outcomes...
August 14, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28807188/the-global-burden-of-tuberculosis-mortality-in-children-a-mathematical-modelling-study
#14
Peter J Dodd, Courtney M Yuen, Charalambos Sismanidis, James A Seddon, Helen E Jenkins
BACKGROUND: Tuberculosis in children is increasingly recognised as an important component of the global tuberculosis burden, with an estimated 1 million cases in 2015. Although younger children are vulnerable to severe forms of tuberculosis disease, no age-disaggregated estimates of paediatric tuberculosis mortality exist, and tuberculosis has never been included in official estimates of under-5 child mortality. We aimed to produce a global mortality burden estimate in children using a complementary approach not dependent on vital registration data...
September 2017: Lancet Global Health
https://www.readbyqxmd.com/read/28806050/linking-high-throughput-screens-to-identify-moas-and-novel-inhibitors-of-mycobacterium-tuberculosis-dihydrofolate-reductase
#15
John P Santa Maria, Yumi Park, Lihu Yang, Nicholas Murgolo, Michael D Altman, Paul Zuck, Greg Adam, Chad Chamberlin, Peter Saradjian, Peter Dandliker, Helena I M Boshoff, Clifton E Barry, Charles Garlisi, David B Olsen, Katherine Young, Meir Glick, Elliott Nickbarg, Peter S Kutchukian
Though phenotypic and target-based high-throughput screening approaches have been employed to discover new antibiotics, the identification of promising therapeutic candidates remains challenging. Each approach provides different information, and understanding their results can provide hypotheses for mechanism of action (MoA) and reveal actionable chemical matter. Here we describe a framework for identifying efficacy targets of bioactive compounds. High throughput biophysical profiling against a broad range of targets coupled with machine learning is employed to identify chemical features with predicted efficacy targets for a given phenotypic screen...
August 14, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28803072/palliative-care-development-in-tajikistan
#16
Nigora Abidjanova
Tajikistan's health system has undergone a series of complex changes associated with reforms aimed at the transition to a more sophisticated control mechanism, financing and operation. As in many developing countries, there is an increase in morbidity and mortality from cancer and chronic diseases, including tuberculosis and HIV. Attention is needed by the state for the development of cost-effective palliative care that will be integrated into the existing public health system. A recent palliative care country needs assessment identified the following areas of work that need to be addressed for palliative care to be implemented: • educating and training of health care professionals, • raising public awareness about palliative care, • making essential palliative care medicines available, • developing the necessary regulatory documents for palliative care development, • developing educational curricula and materials, • integrating palliative care into the medical and nursing universities and schools, • Creating models of palliative care services for home and inpatient facilities...
August 9, 2017: Journal of Pain and Symptom Management
https://www.readbyqxmd.com/read/28802412/mycobacterium-tuberculosis-sige-mutant-st28-used-as-a-vaccine-induces-protective-immunity-in-the-guinea-pig-model
#17
JoLynn Troudt, Elizabeth Creissen, Linda Izzo, Helle Bielefeldt-Ohmann, Stefano Casonato, Riccardo Manganelli, Angelo A Izzo
With more than 9 million new infections and 1.5 million deaths claimed every year, tuberculosis remains one of the major scourges of humankind. The only vaccine available against this disease, the attenuated strain Mycobacterium bovis, BCG is effective against severe forms of the disease in infants, but scarcely effective in protecting adults from the pulmonary form of the disease, thus not stopping transmission. Consequently, the development of an effective anti-tuberculosis vaccine is a major goal for improving global health...
September 2017: Tuberculosis
https://www.readbyqxmd.com/read/28802411/the-minipig-as-an-animal-model-to-study-mycobacterium-tuberculosis-infection-and-natural-transmission
#18
Laylaa Ramos, Andres Obregon-Henao, Marcela Henao-Tamayo, Richard Bowen, Joan K Lunney, Mercedes Gonzalez-Juarrero
In endemic countries more than 20% of tuberculosis (TB) cases are in infants and children. Current animal models study TB during adulthood but animal models for infant TB are scarce. Here we propose that minipigs can be used as an animal model to study adult, adolescent and infant TB including natural transmission. In these studies, two-month old minipigs (representing infant age in humans) and six-month old minipigs (representing adolescence in humans) were infected via the aerosol route with hyper-virulent clinical strain W-Beijing Mycobacterium tuberculosis (Mtb) HN878 and were monitored for 11 or 36 weeks post-challenge, respectively...
September 2017: Tuberculosis
https://www.readbyqxmd.com/read/28802398/a-mycobacterial-growth-inhibition-assay-mgia-for-bovine-tb-vaccine-development
#19
Ilaria Pepponi, Bhagwati Khatri, Rachel Tanner, Bernardo Villarreal-Ramos, Martin Vordermeier, Helen McShane
Human tuberculosis remains a significant cause of mortality and morbidity throughout the world. The global economic impact of bovine TB is considerable. An effective vaccine would be the most cost-effective way to control both epidemics, particularly in emerging economies. TB vaccine research would benefit from the identification of an immune correlate of protection with which vaccines could be gated at both preclinical and clinical levels. In-vitro mycobacterial growth inhibition assays (MGIA) are functional assays that include most aspects of the complex host immune response to mycobacteria, and they may serve as functional immune correlates for vaccine development...
September 2017: Tuberculosis
https://www.readbyqxmd.com/read/28802396/host-genetics-in-susceptibility-to-and-severity-of-mycobacterial-diseases
#20
REVIEW
A S Apt, N N Logunova, T K Kondratieva
The genetic analysis of susceptibility to infections has proven to be extremely useful for identification of key cells, molecules, pathways, and genes involved in the battle between two genomes - the essence of the infectious process. This is particularly true for tuberculosis and other mycobacterial infections which traditionally attracted much attention from both immunologists and geneticists. In this short review, we observe results of genetic studies performed in human populations and in animal models and compare relative input of forward and reverse genetic approaches in our knowledge about genetic control of and immune responses to mycobacterial infections...
September 2017: Tuberculosis
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