Download or read book Catalogue of mutations in Mycobacterium tuberculosis complex and their association with drug resistance written by World Health Organization and published by World Health Organization. This book was released on 2023-11-14 with total page 140 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Catalogue of mutations in Mycobacterium tuberculosis complex and their association with drug resistance written by and published by World Health Organization. This book was released on 2021-06-30 with total page 96 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Exploring the Evolution of Drug Resistance in Mycobacterium Using Whole Genome Sequencing Data written by Dillon Muzondiwa and published by . This book was released on 2019 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Mycobacterium tuberculosis (Mtb) remains a global challenge that has been worsened by the emergence of drug resistant strains of Mtb. We used publicly available Next Generation Sequencing (NGS) and drug susceptibility (DST) data to develop aÌ22́Ơ¿3Resistance snifferaÌ22́Ơ℗+, an online software program for the rapid prediction of lineage and Mtb drug resistance. Based on the distribution of polymorphisms in the genomes of Mtb, we calculated the power of association between the polymorphisms in different clades of Mtb and resistance to 13 anti-TB drugs. Our data suggests that the development of drug resistance in Mtb is a stepwise process that involves the accumulation of polymorphisms in the Mtb genome. We carefully curated the polymorphisms based on their association powers to create a diagnostic key that captures patterns of these polymorphisms that can be used to predict lineage and drug resistance in Mtb. This diagnosis key was incorporated into the Resistance Sniffer tool, an online software program that we developed for the rapid diagnosis of drug resistance in Mtb. The tool was tested using sequence data from the South Africa Medical Research Council (SA-MRC). Our data suggests that the majority of the strains in SA may have been brought by the arrival of European settlers while the more resistant strains may have been introduced in the region by Asian travellers later on. We next sought to determine non-random associations between polymorphic sites in genomes of Mtb. Using the attributable risk (Ra) statistical methods, we distinguished between functional associations and associations that may have been due to genetic drift events for different Mtb clades. We then integrated the (Ra) data with drug susceptibility and annotation data to generate networks in Cytoscape 3.71. These networks were then used to infer evolutionary trajectories that drive the emergence and fixation of the drug resistant phenotype in different clades of Mtb. We demonstrate that strains from the Lineage 1.2 are associated with less complex functional associations compared to the strains from other clades such as the Asian and Euro-American clades. Our data also shows that the predisposition of strains from the Asian clades to develop multi-drug resistance may be attributed to a complex network of functional interactions of mutations in genes that are involved in several aspects of Mtb physiology such as cell wall modelling, lipid metabolism, stress response and DNA repair.

Download or read book Laboratory Methods for Clinical and Public Health written by George P. Kubica and published by . This book was released on 1967 with total page 96 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Strain Variation in the Mycobacterium tuberculosis Complex Its Role in Biology Epidemiology and Control written by Sebastien Gagneux and published by Springer. This book was released on 2017-11-06 with total page 319 pages. Available in PDF, EPUB and Kindle. Book excerpt: Until about 10 years ago, the general view in the field was that Mycobacterium tuberculosis, the causative agent of human tuberculosis was a “clone” with insufficient natural sequence variation between clinical strains to be considered biologically and epidemiologically “relevant”. This view has now changed quite dramatically thanks to the –omics revolution, particularly the advent of next generation DNA sequencing. Large-scale comparative genomic studies over the last few years have revealed that M. tuberculosis clinical strains are more genetically diverse than appreciated previously. Moreover, an increasing number of experimental and epidemiological studies are showing that this genetic diversity also translates into important phenotypic variation. Taken together, these findings have led to a paradigm shift, such that currently phylogenetic diversity among M. tuberculosis clinical strains is being considered in the development of new tools to combat tuberculosis. The purpose of this book is to bring together a series of contributions from some of the most influential groups working on various aspects of M. tuberculosis diversity, and which through their work have contributed to the this paradigm shift. This includes authors focusing on the evolution of M. tuberculosis in relation to other members of the M. tuberculosis complex adapted to animals, the co-evolution between M. tuberculosis and humans, the phenotypic consequences of strains diversity both from an experimental and epidemiological point of view, the ecology and evolution of drug resistant tuberculosis, the diversity and evolution of the BCG vaccine strains, and the use of mathematical modelling to study strain diversity and drug resistance in human tuberculosis. No such book has ever been published, and given the paradigm shift described above, this book will be a valuable resource both for established researchers as well as new scientists, clinicians and public health officials joining the growing field of tuberculosis research.

Download or read book Use of Next generation Sequencing Technologies for the Detection of Mutations Associated with Drug Resistance in Mycobacterium Tuberculosis Complex Technical Guide written by world health organization and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Molecular Epidemiology Study of Mycobacterium Tuberculosis Complex written by Yogendra Shah and published by BoD – Books on Demand. This book was released on 2021-09-15 with total page 122 pages. Available in PDF, EPUB and Kindle. Book excerpt: Tuberculosis (TB), which is caused by the infectious agent Mycobacterium tuberculosis (MTB), is a major global public health problem that infects one third of the world’s population. This book provides an overview of the molecular epidemiology pattern, transmission dynamics, host response, evolution, and pathogenesis mechanisms of TB. Chapters explore such topics as mechanisms associated with increasing trends of drug-resistant TB, the development of anti-mycobacterial drugs, genotyping tools, diagnosis and treatment of latent tuberculosis infection, and more.

Download or read book Identification of Multiple and Novel Drug Resistance in Mycobacterium Tuberculosis Utilizing Protein protein Interaction Networks written by and published by . This book was released on 2018 with total page 75 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mycobacterium tuberculosis (Mtb) is one of the deadliest diseases. While antibiotics exist to treat it, their efficacy has waned in recent years due to drug-resistant strains of the bacteria. While there are methods to detect drug resistance in Mtb, there are potentially mutations which the bacteria harbor that could explain multiple resistances simultaneously, as well as explain novel mechanisms of drug resistance. Towards the identification of multiple and novel drug resistance mutations in Mtb, we analyzed the results of whole genome sequencing for 5,958 Mtb isolates using a three-part approach. We used the protein-protein interaction network for Mtb in the STRING database to identify mutant proteins which were incident to two, or once removed from being incident to two proteins from an original protein set known to cause drug resistance in the bacteria in part one. In the second part, the set of starting proteins was changed to include any two mutated proteins between two isolates with unknown drug resistance to a certain antibiotic. In the last part, the entire network was clustered using an algorithm SPICi, and the most mutated clusters in unknown resistance isolates were determined and functionally characterized using Gene Ontology terms. The proteins which most commonly appeared between double-resistant isolates were GrcC2, associated with isoprenoid biosynthesis in aminoglycoside and pyrazinamide resistance. Mutations in proteins associated with ESX secretion systems were found to correlate to fluoroquinolone single resistance. When using a set of all mutated proteins between two drug resistant isolates, many hypothetical genes were identified as potentially important, however they normally have ill-defined functional roles. The most mutated cluster in drug resistant isolates included PE_PGRS49 and PE_PGRS50, both part of a grouping of proteins in Mtb called PE/PPE proteins which also have murky functional annotation. The other most represented clusters were heavy in lipid metabolism, and also vitamin metabolism, which could be an interesting initiating point for future studies. Overall, the results of this study were exploratory, with mostly poor correlation and low sensitivity and specificity. If experimentally validated, the multiple and novel mechanisms of drug resistance identified herein may be corroborated.

Download or read book New Approaches Against Drug Resistant M tuberculosis written by Maria Rosalia Pasca and published by Frontiers Media SA. This book was released on 2021-06-09 with total page 153 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Rapid Detection of Genetic Mutations Associated with Drug resistant Mycobacterium Tuberculosis written by and published by . This book was released on 2015 with total page 89 pages. Available in PDF, EPUB and Kindle. Book excerpt: Background: Drug resistance continues to threaten recent global progress toward tuberculosis (TB) control. Rapid and accurate detection of resistance is imperative for successful treatment outcomes and reduction in transmission of resistant strains. Methods: Global frequency and distribution of mutations associated with isoniazid resistance were characterized through an exhaustive systematic literature review. The diagnostic performance of a newly redesigned line probe assay (LPA) among both Acid Fast Bacilli (AFB) smear positive and negative specimens was evaluated using cross-sectional data from a large multisite diagnostic study. Additionally, the association of clinical characteristics and valid test results (susceptible or resistant) was assessed using logistic regression. Individual probe results from two LPAs were compared to both sequencing data and phenotypic susceptibility results, and the relative contribution of absent wild type probe hybridization to the detection of phenotypic resistance was determined by comparing the areas under the receiver operating characteristic curves. Results: Globally 64% of isoniazid resistant specimens harbor the katG315 mutation and 19% harbor the inhA-15 mutation, together these two mutations are associated with 80% of isoniazid resistance. Sensitivity and specificity of the LPA for multidrug-resistant TB detection were 95.1% (95%CI 92.6, 96.9) and 99.1% (95%CI 97.1, 100.0) respectively, among both AFB smear positive and negative specimens. Sensitivity for isoniazid resistance was significantly lower among AFB smear negative specimens at 81.6% (95%CI 65.1, 91.7) compared to 94.9% (95%CI 92.4, 96.6) among AFB smear positive specimens. Additionally, AFB smear gradation was significantly associated with valid test results after controlling for HIV status, diabetic status, body mass index, and history of previous treatment. The inclusion of absent wild type probe hybridization in resistance classification for LPAs significantly improved detection of both rifampicin and flouroquinolone phenotypic resistance (P

Download or read book Nanotechnology Based Approaches for Tuberculosis Treatment written by Prashant Kesharwani and published by Academic Press. This book was released on 2020-06-10 with total page 284 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nanotechnology Based Approaches for Tuberculosis Treatment discusses multiple nanotechnology-based approaches that may help overcome persisting limitations of conventional and traditional treatments. The book summarizes the types of nano drugs, their synthesis, formulation, characterization and applications, along with the most important administration routes. It also explores recent advances and achievements regarding therapeutic efficacy and provides possible future applications in this field. It will be a useful resource for investigators, pharmaceutical researchers, innovators and scientists working on technology advancements in the areas of targeted therapies, nano scale imaging systems, and diagnostic modalities in tuberculosis. Addresses the gap between nanomedicine late discovery and early development of tuberculosis therapeutics Explores tuberculosis nanomedicine standardization and characterization with newly developed treatment, diagnostic and treatment monitoring modalities Covers the field thoroughly, from the pathogenesis of tuberculosis and multi-drug resistant mycobacterium tuberculosis, to treatment approaches using nanotechnology and different nanocarriers

Download or read book Mutation and Methylation Mechanisms of Rifampicin Resistance in Mycobacterium Tuberculosis written by and published by . This book was released on 2016 with total page 72 pages. Available in PDF, EPUB and Kindle. Book excerpt: Rifampicin (RIF) is a first-line drug used to treat Mycobacterium tuberculosis (Mtb). Resistance to RIF is predominantly associated with chromosomal mutations in the rpoB gene. This study sought to determine the mutations that explained RIF resistance in a set of 347 isolates (303 resistant, 44 susceptible). The promoter regions of three efflux pump genes, emrB, pstB, and drrA, were also examined for mutations that may confer RIF resistance. Eight RIF-resistant isolates lacked genetic explanation for their resistance but had good sequencing coverage, and eight RIF-susceptible isolates contained mutations reported to confer resistance to RIF. The lack of explanation for the resistance of several isolates raises the questions as to whether current diagnostic methods are reliable enough to detect low-level resistance to rifampicin, and whether there are other mechanisms of resistance that are not yet fully understood. For this reason, the DNA methylation patterns of our isolates, especially those lacking explanation, were examined for associations that would provide insight into other potential mechanisms of resistance. It was found that the unexplained RIF-R isolates had methylation patterns that were comparable to reported drug-tolerant populations, and lacked methylation of several drug effluxing pump genes, suggesting a possible combination of both drug tolerance and (over)expression of efflux pumps as a potential mechanism of resistance. The mechanisms of drug resistance in Mtb maybe more dynamic than currently presumed, and the common mechanism of genetic mutation may eventually be outcompeted by a more adaptive and virulent population of Mtb that is able to respond to a changing environment more quickly. This includes the more immediate benefits that might result from both drug effluxing and the control of gene expression via methylation (which may contribute to the potential for drug tolerance); both of these mechanisms may allow the bacteria to survive long enough to either develop more permanent solutions like genetic mutations or to persist in the presence of the drug during the treatment period. Though these conclusions are daunting, they may provide a more robust picture of the evolution and adaptation of Mtb that could help prevent the exacerbation of drug resistance in the future.

Download or read book Drug Resistance in Mycobacterium Tuberculosis written by Katia Peñuelas-Urquides and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Tuberculosis (TB) remains to be a serious health problem worldwide. There is an increased transmission of Mycobacterium tuberculosis strains with drug resistance, hence complicating TB control. The deciphering of the M. tuberculosis genome, together with the implementation of new molecular biology tools, has allowed the identification of changes in nucleic acid sequences with a functional impact. These mutations have become important in the design of early-diagnostic kits to identify the resistance profile of M. tuberculosis. Since the conventional methods to determine the identity of M. tuberculosis strains based in cultures are laborious, time-consuming and performed by specialized technicians, the result is generated until 4 months after receiving the samples. During this time, patients with TB are not adequately treated, and resistant strains may be transmitted to the rest of the population. In this chapter, we describe the most relevant mutations in genes associated with drug resistance in M. tuberculosis, the analysis of gene expression to identify new markers of drug resistance strains, and the development of new antituberculosis drugs against drug-resistant strains.

Download or read book Pathogenesis of Mycobacterium tuberculosis and its Interaction with the Host Organism written by Jean Pieters and published by Springer Science & Business Media. This book was released on 2013-12-09 with total page 248 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mycobacterium tuberculosis is one of the most notorious pathogens on earth, causing the death of approximately 1.5 million people annually. A major problem in the fight against tuberculosis is the emergence of strains that have acquired resistance to all available antibiotics. One key to the success of M. tuberculosis as a pathogen is its ability to circumvent host immune responses at different levels. This is not only a result of the special makeup of M. tuberculosis in terms of genetic diversity and DNA metabolism and its possession of specialized secretion systems, but also of its ability to hijack the host’s innate immune defence mechanisms. In this volume, researchers from different disciplines provide a topical overview of the diverse mechanisms that contribute to the virulence of M. tuberculosis, ranging from their genetic, metabolic and molecular makeup, as well as the complex strategies these bacteria utilize to escape immune destruction within infected hosts.

Download or read book WHO consolidated guidelines on tuberculosis Module 4 written by World Health Organization and published by World Health Organization. This book was released on 2022-04-30 with total page 72 pages. Available in PDF, EPUB and Kindle. Book excerpt: Between 2011 and 2019, WHO has developed and issued evidence-based policy recommendations on the treatment and care of patients with DR-TB. These policy recommendations have been presented in several WHO documents and their associated annexes, including the WHO Consolidated Guidelines on Drug Resistant Tuberculosis Treatment, issued by WHO in March 2019. The policy recommendations in each of these guidelines have been developed by WHO-convened Guideline Development Groups, using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to summarize the evidence, and formulate policy recommendations and accompanying remarks. The present WHO Consolidated Guidelines on Tuberculosis, Module 4: Treatment - Drug-Resistant Tuberculosis Treatment includes a comprehensive set of WHO recommendations for the treatment and care of DR-TB. The document includes two new recommendations, one on the composition of shorter regimens and one on the use of the BPaL regimen (i.e. bedaquiline, pretomanid and linezolid). In addition, the consolidated guidelines include existing recommendations on treatment regimens for isoniazid-resistant TB and MDR/RR-TB, including longer regimens, culture monitoring of patients on treatment, the timing of antiretroviral therapy (ART) in MDR/RR-TB patients infected with the human immunodeficiency virus (HIV), the use of surgery for patients receiving MDR-TB treatment, and optimal models of patient support and care. The guidelines are to be used primarily in national TB programmes, or their equivalents in Ministries of Health, and for other policy-makers and technical organizations working on TB and infectious diseases in public and private sectors and in the community.

Download or read book Molecular Characterization of Pyrazinamide Resistance in Mycobacterium Tuberculosis written by Wai-Ting Ko and published by . This book was released on 2017-01-26 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation, "Molecular Characterization of Pyrazinamide Resistance in Mycobacterium Tuberculosis" by Wai-ting, Ko, 高慧婷, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Tuberculosis (TB) is a highly infectious disease that causes the second highest mortality rate in human worldwide. The emergence of multi-drug resistance tuberculosis (MDR-TB) leads to a major public health problem in controlling TB-caused mortality. Pyrazinamide (PZA) is an important first-line drug in the treatment of MDR-TB. However, since the challenge in performing susceptibility test on PZA, World Health Organization has not published any data on the prevalence of PZA resistance in Mycobacterium tuberculosis (M. tuberculosis). Since the occurrence of PZA resistance makes MDR-TB more difficult to treat with poor prognosis, rapid detection method in PZA resistance is urgently needed. Since pncA mutation is highly associated with up to 98% PZA resistant M. tuberculosis strains, it is worthwhile to develop rapid molecular method for detecting PZA resistance. This study aims to identify the mutations in PZA resistant M. tuberculosis strains. The first part of this study aims to characterize the pattern of pncA mutation among PZA-resistant and PZA-susceptible M. tuberculosis using Sanger sequencing method. Among all clinical isolates, 12 out of 29 cases of M. tuberculosis were resistant to PZA. All PZA-resistant M. tuberculosis strains harbored pncA mutation, whereas no known mutations were found among those PZA-susceptible strains, giving the positive predictive value to be 100%. Eight mutation patterns were found among 12 resistant isolates. Four of these pncA mutations have not been described previously by other studies. Study also characterizes the pattern of pncA mutation in 19 sputum specimens, with 2 mutation patterns found. Overall 10 mutation patterns were found in this study. Results show that the mutation of pncA gene is highly associated with PZA-resistant M. tuberculosis. Results also suggest the scattered and more extensive mutations in pncA gene that confer PZA resistance to M. tuberculosis. The second and the last part of this study aims to evaluate the possibility of using molecular method to detect PZA resistance in routine clinical laboratory. Results show that using molecular sequencing to detect PZA resistance can shorten the turnaround time to about 3-4 working days. Since mutation of pncA was scattered along the entire pncA gene, using DNA sequencing approach may be the best strategy for the rapid detection of PZA resistance in M. tuberculosis. DOI: 10.5353/th_b5091359 Subjects: Drug resistance Mycobacterium tuberculosis Multidrug-resistant tuberculosis

Download or read book Report on the Detection of Mutations in Mycobacterium Tuberculosis Genes Associated with Drug Resistance written by Isdore Chola Shamputa and published by . This book was released on 1998* with total page 40 pages. Available in PDF, EPUB and Kindle. Book excerpt: