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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.
Tuberculosis remains one of the main fatal infections in humans. With annual morbidity and mortality rates worldwide of 8 and 2 million cases respectively, the disease is far from being eradicated. In fact, the dangerous liaison between TB and HIV, and the increasing incidences of multidrug resistant strains of Mycobacterium tuberculosis are aggravating the problem. The latest epidemiological data indicate that new drugs and a novel vaccine are urgently needed to control TB adequately. This volume summarizes the state of the art in the prevention, diagnosis and therapy of TB. In addition, the molecular biology of M. tuberculosis and the immunology of the host response are presented. Researchers are beginning to understand how the immune response controls the pathogen quite efficiently, yet fails to eradicate it completely in the 2 billion people worldwide who are infected but do not develop the disease. Finally, recent strategies towards the development of new vaccines are reviewed. Scientists investigating the epidemiology, immunology and molecular biology of TB or engaged in vaccine and drug development as well as physicians and social workers treating TB patients will benefit from this timely overview.
Infectious diseases are the leading cause of death globally, particularly among children and young adults. The spread of new pathogens and the threat of antimicrobial resistance pose particular challenges in combating these diseases. Major Infectious Diseases identifies feasible, cost-effective packages of interventions and strategies across delivery platforms to prevent and treat HIV/AIDS, other sexually transmitted infections, tuberculosis, malaria, adult febrile illness, viral hepatitis, and neglected tropical diseases. The volume emphasizes the need to effectively address emerging antimicrobial resistance, strengthen health systems, and increase access to care. The attainable goals are to reduce incidence, develop innovative approaches, and optimize existing tools in resource-constrained settings.
Tuberculosis control in animals and humans alike requires early detection of Mycobacterium tuberculosis complex as well as current knowledge about the transmission patterns of the disease in the respective populations. These two building blocks provide the foundation on which the disease control programs can build their policies to expediate control efforts. In this thesis we amalgamate molecular epidemiology, genomics, and proteomics. We studied the transmission pattern of M. tuberculosis and its evolution within a marginalized population. The patterns led to the identification of gaps in TB control policies in marginalized populations with little access to healthcare. Similarly, we studied the genomewide polymorphisms in a naturally attenuated strain - M. bovis strain Ravenel to elucidate possible mechanisms for its reduced virulence and pathogenicity. Insights gained from genome sequence analysis in conjunction with pathogenesis study for M. bovis Ravenel paved the pathway to defining the complex and multi-faceted reasons for attenuation of the oldest bacteria of the world. Next, pathogen-specific biomarkers were evaluated to assist in unambiguous disease detection across multiple host species. Discovery and validation of biomarkers work facilitated the field diagnostic applications for TB in animals and humans. This three-pronged approach developed in this study, understanding the genomic basis of attenuation, and enhanced field TB diagnostics in the animal-human interface.
Progress obtained by mycobacteriology in recent years is undeniable with regards to preventing, detecting, and treating cases of tuberculosis, millennial disease that is still present as public health issue worldwide. We present here high-impact research and interest topics related to the application of new methodologies, especially molecular methods for rapid diagnostic such as rapid DST, application of high performance liquid chromatography, molecular epidemiology and molecular diagnostic testing on post mortem. Currently, the constant search for vaccines that prevent the disease is promising through research of the immune response generated by the host towards the bacterium, and the effectiveness that may be achieved from developed vaccines. Another high-impact factor is the one generated by considering tuberculosis as a social disease with an infectious component reflected in research about tuberculosis and human rights. Finally, we present important issues of the pathogen interaction with different hosts. The constant knowledge generation that expands the frontiers of understanding is a key factor for finding solutions and successful activities for public health.
This book will serve as a primer for both laboratory and field scientists who are shaping the emerging field of molecular epidemiology. Molecular epidemiology utilizes the same paradigm as traditional epidemiology but uses biological markers to identify exposure, disease or susceptibility. Schulte and Perera present the epidemiologic methods pertinent to biological markers. The book is also designed to enumerate the considerations necessary for valid field research and provide a resource on the salient and subtle features of biological indicators.
Despite decades of developments in immunization and drug therapy, tuberculosis remains among the leading causes of human mortality, and no country has successfully eradicated the disease. Reenvisioning tuberculosis from the perspective of population biology, this book examines why the disease is so persistent and what must be done to fight it. Treating tuberculosis and its human hosts as dynamic, interacting populations, Christopher Dye seeks new answers to key questions by drawing on demography, ecology, epidemiology, evolution, and population genetics. Dye uses simple mathematical models to investigate how cases and deaths could be reduced, and how interventions could lead to TB elimination. Dye's analysis reveals a striking gap between the actual and potential impact of current interventions, especially drug treatment, and he suggests placing more emphasis on early case detection and the treatment of active or incipient tuberculosis. He argues that the response to disappointingly slow rates of disease decline is not to abandon long-established principles of chemotherapy, but to implement them with greater vigor. Summarizing epidemiological insights from population biology, Dye stresses the need to take a more inclusive view of the factors that affect disease, including characteristics of the pathogen, individuals and populations, health care systems, and physical and social environments. In broadening the horizons of TB research, The Population Biology of Tuberculosis demonstrates what must be done to prevent, control, and defeat this global threat in the twenty-first century.
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.
Bovine tuberculosis (bTB) is a significant zoonotic pathogen with a global distribution, and a considerable economic impact. It has a notoriously complex epidemiology, varying by affected region and often involving multiple-host species. Here we present an international collection of papers that address both national and international factors impacting on the control of bovine tuberculosis. We hope this Research Topic will provide a forum which may generate a greater understanding of the disease in a wider context, and inform future eradication efforts through the design of more effective interventions.
A major objective of this open access book is to summarize the current status of Buruli Ulcer (BU) research for the first time. It will identify gaps in our knowledge, stimulate research and support control of the disease by providing insight into approaches for surveillance, diagnosis, and treatment of Buruli Ulcer. Book chapters will cover the history, epidemiology diagnosis, treatment and disease burden of BU and provide insight into the microbiology, genomics, transmission and virulence of Mycobacterium ulcerans.