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https://www.readbyqxmd.com/read/28533187/host-directed-therapies-offer-novel-opportunities-for-the-fight-against-tuberculosis
#1
REVIEW
Arnaud Machelart, Ok-Ryul Song, Eik Hoffmann, Priscille Brodin
Tuberculosis (TB) remains a leading global health problem that is exacerbated by the emergence of multidrug and extensively drug-resistant Mycobacterium tuberculosis strains. Control of the disease requires novel therapeutic strategies. Modulating host homeostasis appears to be a promising approach, and recent studies have identified novel potential host targets and compounds that could be investigated for host-directed therapies (HDTs). Moreover, the recent development of intracellular high-throughput phenotypic assays makes it possible to screen large libraries of compounds to identify more rapidly new effectors for mycobacterial elimination...
May 19, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28533124/the-novel-gene-mtb192-is-a-candidate-marker-for-the-detection-of-multidrug-resistant-mycobacterium-tuberculosis-strains
#2
Junhua Chen, Li Jiang, Wei Su, Gaihuan Zheng, Xu Hongmei
BACKGROUND: Multi-drug resistant tuberculosis (TB) is one of the most main threats to the global TB control work at present. And it's very difficult to detect. From a screen of differentially expressed genes in multidrug-resistant tuberculosis (MDR-TB) strains, we identified a new gene, mtb192. In the present study, we verified the association of mtb192 with TB drug resistance by detecting its expression in clinical isolates from paediatric TB patients. MATERIALS AND METHODS: The homology of mtb192 was analysed by gene blasting in GenBank...
May 19, 2017: Gene
https://www.readbyqxmd.com/read/28531291/a-novel-virus-vectored-respiratory-mucosal-vaccine-enhances-anti-tuberculosis-immunity-in-a-humanized-model-system
#3
Yushi Yao, Rocky Lai, Sam Afkhami, Siamak Haddadi, Anna Zganiacz, Fatemeh Vahedi, Ali A Ashkar, Charu Kaushic, Mangalakumari Jeyanathan, Zhou Xing
Background: The translation of pre-clinically promising novel tuberculosis (TB) vaccines to ultimate human applications has met with the challenge of lacking markedly improved animal models for vaccine testing with an immune system of human equivalent in its genetic diversity and level of susceptibility to TB. Methods: We have developed a humanized mice (Hu-mice) TB model system to investigate the clinical relevance of a novel virus-vectored (VV) TB vaccine administered via respiratory mucosal (RM) or parenteral route...
May 20, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28522990/animal-models-for-tuberculosis-in-translational-and-precision-medicine
#4
REVIEW
Lingjun Zhan, Jun Tang, Mengmeng Sun, Chuan Qin
Tuberculosis (TB) is a health threat to the global population. Anti-TB drugs and vaccines are key approaches for TB prevention and control. TB animal models are basic tools for developing biomarkers of diagnosis, drugs for therapy, vaccines for prevention and researching pathogenic mechanisms for identification of targets; thus, they serve as the cornerstone of comparative medicine, translational medicine, and precision medicine. In this review, we discuss the current use of TB animal models and their problems, as well as offering perspectives on the future of these models...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28522424/cyclodextrin-based-nanocarriers-containing-a-synergic-drug-combination-a-potential-formulation-for-pulmonary-administration-of-antitubercular-drugs
#5
Giuseppina Salzano, Jitendra Wankar, Stefano Ottani, Baptiste Villemagne, Alain R Baulard, Nicolas Willand, Priscille Brodin, Ilse Manet, Ruxandra Gref
Tuberculosis (TB) remains a major global health problem. The use of ethionamide (ETH), a main second line drug, is associated to severe toxic side-effects due to its low therapeutic index. In this challenging context, "booster" molecules have been synthetized to increase the efficacy of ETH. However, the administration of ETH/booster pair is mostly hampered by the low solubility of these drugs and the tendency of ETH to crystallize. Here, ETH and a poorly water-soluble booster, so-called BDM43266, were simultaneously loaded in polymeric β-cyclodextrin nanoparticles (pβCyD NPs) following a "green" protocol...
May 15, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28507893/delayed-diagnosis-of-severe-tuberculous-spondylodiscitis-in-an-asylum-seeker-patient-or-doctors-delay
#6
Kristina Langholz Kristensen, Daria Podlekareva, Pernille Ravn
The still increasing global migration affects the epidemiology of tuberculosis (TB) in European countries. We present the case of an asylum seeker from a TB high-endemic country, who presented with severe TB spondylodiscitis and need for emergency surgery. The patient had a history of recurrent sterile axillary and perianal abscesses for years, but TB was never properly ruled out. The patient underwent surgery, responded well to antibiotics and regained the ability to walk. After 6 month of treatment the patient was lost to follow-up...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28507027/mycobacterium-tuberculosis-lipoprotein-mpt83-induces-apoptosis-of-infected-macrophages-by-activating-the-tlr2-p38-cox-2-signaling-pathway
#7
Lin Wang, Mianyong Zuo, Hao Chen, Siyu Liu, Xiangyang Wu, Zhenling Cui, Hua Yang, Haipeng Liu, Baoxue Ge
Tuberculosis caused by Mycobacterium tuberculosis continues to pose a serious global health threat. The attenuated Mycobacterium bovis bacillus Calmette-Guérin, as the only licensed vaccine, has limited protective efficacy against TB. The development of more effective antituberculosis vaccines is urgent and demands for further identification and understanding of M. tuberculosis Ags. MPT83 (Rv2873), a secreted mycobacterial lipoprotein, has been applied into subunit vaccine development and shown protective effects against M...
May 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28506215/comparison-of-antibody-responses-against-mycobacterium-tuberculosis-antigen-rv0679c-in-tuberculosis-patients-from-the-endemic-and-non-endemic-regions-of-the-beijing-genotype-a-case-control-study
#8
Jingge Zhao, Takashi Matsuba, Xiaoyan Zhang, Susan Leano, Chie Nakajima, Haorile Chagan-Yasutan, Elizabeth Freda Telan, Yasuhiko Suzuki, Toshio Hattori
BACKGROUND: Strains of the Beijing genotype of Mycobacterium tuberculosis (MTB) are reportedly associated with the virulence of tuberculosis (TB) infection, unfavorable outcomes of anti-TB treatment, and the global TB pandemic. Rv0679c, a hypothetical membrane protein related to host cell invasion, has a Beijing genotype-specific mutation at residue 142 (Asn142Lys). Antigenicity differences between Rv0679c-Asn142 (N-type) and Rv0679c-Lys142 (K-type) have been previously observed in mice antigen-antibody responses...
May 15, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28504628/-the-current-global-tuberculosis-state
#9
Christian Wejse, Troels Lillebæk, Ole Kirk, Pernille Ravn, Isik Somuncu Johansen, Åse Bengård Andersen
Despite an increase in the total number of tuberculosis (TB) patients globally, positive trends in reduction of prevalence and mortality are observed. However, high numbers of drug-resistant cases are threatening this trend. Multidrug-resistant and extensively resistant cases constitute an increasing challenge in many parts of the world also within the European region - especially in former Sovjet Republic nations. Point-of-care test systems potentially replacing microscopy and urine antigen detection systems are currently launched in many TB-high endemic countries improving TB detection rates...
May 15, 2017: Ugeskrift for Laeger
https://www.readbyqxmd.com/read/28499828/estimating-the-future-burden-of-multidrug-resistant-and-extensively-drug-resistant-tuberculosis-in-india-the-philippines-russia-and-south-africa-a-mathematical-modelling-study
#10
Aditya Sharma, Andrew Hill, Ekaterina Kurbatova, Martie van der Walt, Charlotte Kvasnovsky, Thelma E Tupasi, Janice C Caoili, Maria Tarcela Gler, Grigory V Volchenkov, Boris Y Kazennyy, Olga V Demikhova, Jaime Bayona, Carmen Contreras, Martin Yagui, Vaira Leimane, Sang Nae Cho, Hee Jin Kim, Kai Kliiman, Somsak Akksilp, Ruwen Jou, Julia Ershova, Tracy Dalton, Peter Cegielski
BACKGROUND: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are emerging worldwide. The Green Light Committee initiative supported programmatic management of drug-resistant tuberculosis in 90 countries. We used estimates from the Preserving Effective TB Treatment Study to predict MDR and XDR tuberculosis trends in four countries with a high burden of MDR tuberculosis: India, the Philippines, Russia, and South Africa. METHODS: We calibrated a compartmental model to data from drug resistance surveys and WHO tuberculosis reports to forecast estimates of incident MDR and XDR tuberculosis and the percentage of incident MDR and XDR tuberculosis caused by acquired drug resistance, assuming no fitness cost of resistance from 2000 to 2040 in India, the Philippines, Russia, and South Africa...
May 9, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28499455/bovis-bacillus-calmette-guerin-bcg-infection-induces-exosomal-mirna-release-by-human-macrophages
#11
Shamila D Alipoor, Esmaeil Mortaz, Payam Tabarsi, Parissa Farnia, Mehdi Mirsaeidi, Johan Garssen, Masoud Movassaghi, Ian M Adcock
BACKGROUND: Tuberculosis (TB) remains a significant global health concern and its diagnosis is challenging due to the limitations in the specificity and sensitivity of the current diagnostic tests. Exosomes are bioactive 30-100 nm vesicles produced by most cell types and are found in almost all human body fluids. Exosomal microRNAs (miRNAs) can transfer biological information between cells and tissues and may act as potential biomarkers in many diseases. In this pilot study, we assessed the miRNA profile of exosomes released from human monocyte-derived macrophages upon infection with Mycobacterium bovis Bacillus Calmette-Guerin (BCG)...
May 12, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28486981/patients-willingness-to-pay-for-the-treatment-of-tuberculosis-in-nigeria-exploring-own-use-and-altruism
#12
Ogbonnia G Ochonma, Obinna E Onwujekwe
BACKGROUND: Although, current treatment services for Tuberculosis (TB) in Nigeria are provided free of charge in public facilities, the benefits (value) that patients attach to such service is not known. In addition, the prices that could be charged for treatment in case government and its partners withdraw from the provision of free services or inclusion of the services in health insurance plans are not known. Hence, there is a need to elicit the maximum amounts that patients are willing to pay for TB treatment services, both for themselves and for the very poor patients that may not be able to pay if some user fees are introduced (altruistic willingness to pay)...
May 10, 2017: International Journal for Equity in Health
https://www.readbyqxmd.com/read/28485693/rapid-assessment-of-facilitators-and-barriers-related-to-the-acceptance-challenges-and-community-perception-of-daily-regimen-for-treating-tuberculosis-in-india
#13
Himanshu Negandhi, Ritika Tiwari, Anjali Sharma, Rajesh Nair, Sanjay Zodpey, Ramesh Reddy Allam, Ganesh Oruganti
INTRODUCTION: The Revised National Tuberculosis Control Program (RNTCP) is the largest tuberculosis (TB) control program in the world based on Directly Observed Treatment Short-Course (DOTS) strategy. Globally, most countries have been using a daily regimen and in India a shift towards a daily regimen for TB treatment has already begun. The daily strategy is known to improve program coverage along with compliance. Such strategic shifts have both management and operational implications...
2017: Global Health Action
https://www.readbyqxmd.com/read/28485504/mechanistic-principles-behind-molecular-mechanism-of-rifampicin-resistance-in-mutant-rna-polymerase-beta-subunit-of-mycobacterium-tuberculosis
#14
Aditi Singh, Sonam Grover, Sidhartha Sinha, Mriganko Das, Pallavi Somvanshi, Abhinav Grover
Evolution of drug resistant Mycobacterium strains threatens the TB treatment and control programs globally. Rifampicin (RIF) is an important first line antitubercular drug. Resistance to Rifampicin is caused mainly by mutations in its target RNA polymerase beta subunit protein (RpoB). RpoB contains a Rifampicin resistance determining region (RRDR) and has several potent sites for mutations. In this study, we have investigated mutations of a single site (H451) to eight different amino acids, involved in RIF resistance...
May 9, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28482956/tuberculosis-in-migrants-in-low-incidence-countries-epidemiology-and-intervention-entry-points
#15
K Lönnroth, Z Mor, C Erkens, J Bruchfeld, R R Nathavitharana, M J van der Werf, C Lange
As tuberculosis (TB) rates continue to decline in native populations in most low TB incidence countries, the proportion of TB patients born outside their country of residence ('foreign-born') increases. Some low-incidence countries have experienced a substantial increase in TB rates related to recent increases in the number of asylum seekers and other migrants from TB-endemic countries. However, average TB rates among the foreign-born in low-incidence countries declined moderately in 2009-2015. TB in foreign-born individuals is commonly the result of reactivation of latent infection with Mycobacterium tuberculosis acquired outside the host country...
June 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28482955/an-overview-of-tuberculosis-and-migration
#16
P Dhavan, H M Dias, J Creswell, D Weil
With nearly one billion migrants worldwide, migration is both a dynamic and a divisive phenomenon facing the world today. Migrants are a heterogeneous group, and the conditions surrounding migration pathways often pose risks to the physical, mental and social well-being of migrants, with certain subgroups being more vulnerable than others. Several determinants of health and tuberculosis (TB) interplay to increase the vulnerability of migrants to tuberculous infection, TB disease and poor treatment outcomes, making them a key population for TB...
June 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28482954/multidrug-resistant-tuberculosis-treatment-programmes-insufficiently-consider-comorbid-mental-disorders
#17
I F Walker, S C Baral, X Wei, R Huque, A Khan, J Walley, J N Newell, H Elsey
The successful treatment of multidrug-resistant tuberculosis (MDR-TB) is a global health priority and a key pillar of the World Health Organization's (WHO's) End TB strategy. There has been significant global investment in diagnostic capabilities in recent years. However, we argue that the mental distress of those with MDR-TB and their families continues to be overlooked by TB programmes. Priorities in the End TB Strategy of 'patient-centred care' and 'patient support' are still to be delivered in practice in many low-income settings, and in particular consideration of mental distress...
June 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28482292/new-drugs-for-the-treatment-of-mycobacterium-tuberculosis-infection
#18
REVIEW
Manaf AlMatar, Husam AlMandeal, Işıl Var, Begüm Kayar, Fatih Köksal
Tuberculosis presents a grave challenge to health, globally instigating 1.5 million mortalities each year. Following the breakthrough of first-line anti-TB medication, the number of mortalities reduced greatly; nonetheless, the swift appearance of tuberculosis which was drug-resistant, as well as the capability of the bacterium to survive and stay dormant are a considerable problem for public health. In order to address this issue, several novel possible candidates for tuberculosis therapy have been subjected to clinical trials of late...
May 5, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28480928/differential-flap-dynamics-in-l-d-transpeptidase2-from-mycobacterium-tuberculosis-revealed-by-molecular-dynamics
#19
Zeynab Fakhar, Thavendran Govender, Glenn E M Maguire, Gyanu Lamichhane, Ross C Walker, Hendrik G Kruger, Bahareh Honarparvar
Despite the advances in tuberculosis treatment, TB is still one the most deadly infectious diseases and remains a major global health quandary. Mycobacterium tuberculosis (Mtb) is the only known mycobacterium with a high content of 3→3 crosslinks in the biosynthesis of peptidoglycan, which is negligible in most bacterial species. An Mtb lacking LdtMt2 leads to alteration of the colony morphology and loss of virulence which makes this enzyme an attractive target. Regardless of the vital role of LdtMt2 for cell wall survival, the impact of ligand binding on the dynamics of the β-hairpin flap is still unknown...
May 8, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28479569/a-web-based-tool-to-enhance-monitoring-and-retention-in-care-for-tuberculosis-affected-patients
#20
Barbara Giannini, Niccolò Riccardi, Antonio Di Biagio, Giovanni Cenderello, Mauro Giacomini
Tuberculosis (TB) is responsible for a global epidemic. TB treatment requires long-term therapy usually with multiple drugs, which have potential side effects and interactions that may influence patients' adherence to treatment. The TB Ge network is a multi-centric web based platform that collects clinical information of TB affected patients to increase their support and retention in care. The system stores the list of all tuberculosis episodes for each patient with the related data, starting from the first visit including follow-ups clinical evaluations, laboratory tests, imaging and therapies...
2017: Studies in Health Technology and Informatics
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