Preface and Introduction

The Revised Authoritative Guide To Vaccine Legal Exemptions

Vaccines Have Serious Side Effects

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The summer of 2006 marked the 30th anniversary of the outbreak of Legionnaires' disease, an acute pneumonia that occurred among veterans who had gathered in Philadelphia, Pennsylvania, in 1976 to celebrate the bicentennial of the founding of the United States. Ironically, the nation and world were braced for an epidemic of swine influenza, which never materialized and no one expected the emergence of a new bacterial pathogen, since most in the medical field sincerely believed that all the pathogens of humans were now known. This new bacterial agent of Legionnaires' disease, Legionella pneumophila (named in memory of the deceased veterans) was a harbinger of diseases to come (emerging pathogens) that has included HIV/AIDS, SARS, Lyme disease, hamburger disease, and many others. The further discovery that L. pneumophila was ubiquitous to aquatic environments worldwide and resided as an intracellular parasite of amoeba and protozoa provided a link between natural environments and human disease. Thus, environmental monitoring, especially of potable water, cooling towers, and related sources, has become a major focus in efforts to control the spread of this disease. Fortunately, as noted in the 1976 epidemic and holds true today, the disease is not spread from human to human. The remarkable ability of L. pneu-mophila to multiply in alveolar macrophages, as if they were amoebae, has further contributed to our understanding of the disease and stimulated much research in the area of cellular microbiology of pathogenesis.

Today, Legionnaires' disease is both sporadic (community acquired) and epidemic (explosive point sources such as cooling towers) and is on the rise worldwide - attributed to a greater dependence on technology and air conditioning together with an increasingly susceptible population due to medical technology. Despite all the advances in medicine, Legionnaires' disease continues to have a high mortality rate, not uncommon when pneumonia is involved. Advances in understanding pathogenesis and immunity have benefited greatly from the availability of three genome sequences for L. pneumophila and one for close relative Coxiella burnetii. Both Legionella and Coxiella produce survival forms and display a developmental cycle which contribute to pathogenesis, persistence, and resistance to biocides in natural environments. There have been many major developments in the Legionella field ranging from strategies to treat infections to how

Xiii this organism interacts with innate immune mechanisms to promote infections. This book represents the first collection of chapters written by experts in each of the specialty areas in this field. Unlike past books, which have been proceedings from international meetings, we have provided an opportunity for each of the authors to present "state of the art" detailed descriptions of specific areas that permit interesting reading for the non-expert and a solid reference for those researchers active in this field.

The authors of each of the chapters in this book are internationally recognized experts concerning Legionella infections. The first chapter by Drs. Christel Caza-let and Carmen Buchreiser from the Institute Pasteur, Paris, France, concerns the molecular biology and genetics of L. pneumophila pathogenesis. The authors describe in-depth laboratory investigations of the genetic differences between the numerous strains of these opportunistic bacteria and provide important new information how these microbes interact with environmental factors and their host. The next chapter by Dr. Nicholas Cianciotto, Northwestern University Medical School, Chicago, Illinois, stresses important physiological aspects of Legionella-host interactions, especially the important role of iron assimilation and the nature and mechanism of protein secretion by these bacteria. Drs. J. Le Blanc, Dalhouse University, Halifax, Nova Scotia from Canada, and Joseph P. Vogel from St. Louis, Missouri, then describe the metabolic activity of these ubiquitous microbes, especially the nature and mechanism of their secretion system. Dr. Rafael Garduño, Dalhousie University, Halifax, Nova Scotia Canada, then discusses pathogenesis and immunity to that bacterium, including some unique features of the life as well as developmental cycle of L. pneumophila in a host, both human and protozoa in their natural habitat. Dr. Barry Fields, Centers for Disease Control and Prevention, Atlanta, Georgia, then presents detailed observations how Legionella are widely dispersed in the environment, especially freshwater habitats.

Drs. Rachel Edwards and Michele Swanson, University of Michigan, Ann Arbor, Michigan, describe how the life cycle of these bacteria is regulated and information necessary to control the presence of the bacteria, especially in the environment, and treatment modalities with antibiotics which abrogate bacterial replication and/or disease progression. Although no effective vaccine has yet been developed, information concerning interaction of these Legionella with the human host and how they infect host cells, as well as various antigenic structures of the bacteria important for infectivity and replication, provide a foundation necessary for developing protective vaccines which can induce adaptive immunity. Dr. Paul Hoffman, University of Virginia, provides new information about the interesting unique physiology of L. pneumophila and other species of these bacteria. He compares different aspects of their physiology in the human host vs. replication in amoeba and protozoa.

Dr. Thomas J. Marrie, Walter C. Mackenzie Health Science Center, Edmonton, Alberta, Canada, then describes medical and clinical aspects of Legionnaire's disease which first attracted attention in the epidemic pneumonia outbreak in a hotel in Philadelphia during the annual convention of Pennsylvania State Legionnaires after which the disease is named. His chapter describes clinical aspects of the infection in individuals showing respiratory symptoms. It is also now widely recognized that many individuals have subclinical exposure to Legionella, as evident by high titers of specific humoral antibody and marked in vitro blastogenic responsiveness of their blood lymphocytes to Legionella antigen.

Drs. H. Friedman, C. Newton, and Thomas W. Klein, University of South Florida, discuss in detail the exploding new knowledge concerning immunity to L. pneumophila in terms of newer information about innate and adaptive specific immune responses to these ubiquitous opportunistic intracellular bacteria which primarily cause serious infection in immunocompromised individuals but which have their natural habitat single cell protozoa. They apparently interact with human hosts because of their ubiquitous presence in warm lakes, airconditioning cooling towers, circulating warm water in plumbing, and drinking water in institutions such as hospitals. The next chapter by Drs. J. Rogers, A. Hakki, and H. Friedman, also from the University of South Florida, is concerned with information how nonspecific immune stimulators modify host susceptibility to infection by opportunistic bacteria such as Legionella. This chapter reviews nonspecific modulators of both innate and adaptive immune mechanisms which impact the host immune response to an opportunistic pathogen like Legionella. Plant-derived nonspecific immunoenhancing substances are being investigated worldwide and various small molecular weight substances used for centuries as "folk medicine" to ameliorate infections have been shown clinically to significantly enhance host resistance to ubiquitous microbial infections.

Drs. Maelle Molmeret and Yousef Abu Kwaik, University of Louisville, Louisville, Kentucky, then describe in detail information concerning L. pneumophila interactions with amoeba in vitro. Knowledge about such interactions is important to understand the nature and mechanism whereby these bacteria interact with phagocytic cells of the human host and the many biochemical and physiological features of legionellae common to their uptake and regulation in different cell types.

The editors as well as authors of individual chapters believe the many ongoing studies of host immunity to ubiquitous opportunistic pathogens like L. pneumophila will undoubtedly lead to more effective control methods to prevent or ameliorate infections by such microorganisms, which still account for many thousands of infections annually in the United States alone. Many details concerning the nature and mechanism of interactions between host and opportunistic intracellular organisms like Legionella, which preferentially infect phagocytic cells, are being clarified and provide important knowledge directly related to mechanisms of host resistance to other important intracellular opportunistic pathogens, including Mycobacteria which cause tuberculosis. We thank Ms. Ilona Friedman for continuing excellent editorial assistance correlating and assisting in preparation of manuscripts for this book in the series.

Paul S. Hoffman Herman Friedman Thomas W. Klein

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  • rowan bracegirdle
    What is introduction of demonstrating the ubiquitous nature of microorganisms?
    9 years ago

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