The terrorist use of diseases as bioweapons has been one of the major security concerns in recent years, particularly after the anthrax letter attacks in the USA in 2001. This uncertain threat of intentional outbreaks of diseases exists side by side with the constantly changing very real threat from diseases, epidemics and pandemics as recently illustrated by the H1N1 influenza pandemic, SARS, and H5N1 bird influenza events. This publication contains case studies on the public health planning for (un)usual disease outbreaks for 11 large and small countries with a focus on South Eastern Europe. In many countries, military entities traditionally play an important role in emergency response to disease outbreaks. In smaller countries, very little exists, however, in terms of specific biopreparedness efforts (in both the military and civilian area), which is at least partly due to a relatively low bioterrorism threat perception, and serious resource constraints. The uncertainty associated with the bioterrorism threat makes public health preparedness planning for such events politically and financially very difficult. The similarity of responding to bioterrorism events and natural disease outbreaks from a public health point of view suggests the merit of looking at biopreparedness as a part of overall health emergency planning, not as a separate effort.

In the last ten years, major strides have been made in defining the presence and role of inflammation in atherosclerosis as well as in injury to the tissues that occurs after episodes of ischemia and reperfusion. In sixteen chapters, written by world-renowned individuals from different countries, the role of inflammation and different mediators in the pathogenesis of atherosclerosis is presented. The significance of inflammation and possible therapeutic implications is also described in depth. This book is of great interest for a wide range of physicians, researchers, and scientists who may want to study more and develop the concept of inflammation and atherosclerosis.

This volume is based on the program of the Second International Conference on Drugs of Abuse, Immunity and AIDS, held in Clearwater Beach, FL in June 1992. The Conference was supported in part by the University of South Florida College of MediCine with financial assistance from the National Institute on Drug Abuse. The focus of this conference was the effects of drugs of abuse on immunity. It is now widely recognized that psychoactive drugs of abuse, including marijuana, cocaine, and opiates, as well as alcohol, have marked effects in an individual, including effects on their nervous system and behavior. In the past two decades, the scope of studies concerning the effects of some drugs of abuse have also involved investigations of alterations of various physiologic parameters including effects on the immune system. and the influence of such immune alterations on normal physiological responses. In this regard, participants in this Second International Conference provided newer information concerning both basic and clinical aspects of drugs of abuse and immunity, especially immunodeficiencies. In this regard, advances have been made in recent years concerning the nature and mechanisms whereby the immune system is regulated and the possible mechanisms by which drugs of abuse influence such immune systems. In particular, the emergence of psychoneuroimmunology as a new discipline the last decade has heightened interest in the immune responses influenced by psychoactive drugs. This has resulted in interdisciplinary investigations involving both clinical and basic scientists, including microbiologists, immunologists, physiologists, psychiatrists, oncologists, psychologists, etc.

The National Institute of Dental Research sponsored a workshop on "Genetically Engineered Vaccines: Prospects for Oral Disease Prevention," held at the National Institutes of Health (NIH) on November 6-8, 1991. The purpose of the workshop was to convene molecular biologists and immunologists to address the state of the science in vaccine development and to explore the potential of developing vaccines for prevention of oral diseases. The goal was to elicit new research initiatives and recommendations for vaccine development with emphasis on the prevention of oral diseases and diseases affecting the orofacial tissues. The workshop was attended by more than 100 persons who heard 30 presentations, and the speakers provided the papers for this volume. The workshop focused on the following topics: oral diseases and host immune responses, update on vaccines and vaccine development, vaccines and the mucosal immune system, optimizing mucosal and systemic immune responses, delivery systems and immune analysis, target antigen selection and vaccine development, immunological correlates of protection and future direc tions/recommendations. Three key areas were identified: Optimizing the Mucosal Immune Response, Antigen Delivery Systems, and Target Antigens and Immunological Correlates of Protection. The summary and recommendations from these deliberations is included at the end of this volume."

The terrorist use of diseases as bioweapons has been one of the major security concerns in recent years, particularly after the anthrax letter attacks in the USA in 2001. This uncertain threat of intentional outbreaks of diseases exists side by side with the constantly changing very real threat from diseases, epidemics and pandemics as recently illustrated by the H1N1 influenza pandemic, SARS, and H5N1 bird influenza events. This publication contains case studies on the public health planning for (un)usual disease outbreaks for 11 large and small countries with a focus on South Eastern Europe. In many countries, military entities traditionally play an important role in emergency response to disease outbreaks. In smaller countries, very little exists, however, in terms of specific biopreparedness efforts (in both the military and civilian area), which is at least partly due to a relatively low bioterrorism threat perception, and serious resource constraints. The uncertainty associated with the bioterrorism threat makes public health preparedness planning for such events politically and financially very difficult. The similarity of responding to bioterrorism events and natural disease outbreaks from a public health point of view suggests the merit of looking at biopreparedness as a part of overall health emergency planning, not as a separate effort.

There are only very few chemical classes of antibiotics in medical use, and these have originated over a span of more than 60 years of research. Almost half a century ago, the first member of the macrolides, erythromycin, was introduced as a treatment option for bacterial infections. Erythromycin is a very complex fermentation product obtained from the soil bacterium Saccharopolyspora ery thraea (originally named Streptomyces erythreus). The success of erythromycin, based on its efficacy and tolerability, stimulated researchers throughout the world to undertake intense efforts to understand the biology and chemistry of macrolides and to use this experience to improve the properties of this compound class. The second generation of macrolides, based on chemical modifications of erythromy cin, is currently being in broad use, especially for treatment of respiratory tract infections. We presently foresee the introduction of a new generation of macro lides, i. e. the ketolides, which have the potential to overcome rising resistance problems. This monograph is intended to give the interested reader an overview on "macrolide experience," covering important areas from basic research to clinical use. Starting from a historic overview, the essential basic parameters - efficacy, pharmacokinetics, pharmacodynamics, and pharmacology - are highlighted in order to introduce the reader to the rationale for clinical use of macrolides. The following group of chapters cover the complex chemistry of the macro lactone structures, giving historic background, basic structure-activity relation ships of various derivatization strategies, and perspectives for future discovery of new semisynthetic macrolide antibiotics."

Mycobacteria is divided into two volumes. The first volume deals with the basic biology of mycobacteria. With its emphasis on the state of the art outlook, this volume includes taxonomy and molecular biology of mycobacteria, modern approaches for detection of mycobacteria, and immunology and immunization against tuberculosis. The second volume covers drug trestments for mycobacteria anad tuberculosis. It outlines trends of discovery and development of chemotherapy, starting from the mid-50's to present day uses of chemotherapy in treating AIDS, drug-resistant tuberculosis, and other non-tuberculosis mycobacterial diseases.

This year marks the tenth anniversary of the International Symposium on Medical Virology. In the Foreword to the book of the 1980 Symposium, we stated, "However, the challenges still lying ahead are more numerous than our past accomplishments". Little did we know at the time, that within a few years the spread of human immunodeficiency virus type I was going to occur. This worldwide epidemic has, like no other disease in recent history, awakened the scientific community and the public at large. It is a reminder to all of us that regardless of our vast technical advances, Nature provides such great opportunity for biological diversity, that it will always be one step ahead of our scientific knowledge. Although our understanding of virology, molecular biology and immunology have increased by leaps and bounds over the last decade, we are still at the point of being unable to effectively control the spread of this viral infection. We hope that our Symposium this year has helped researchers to come together and exchange' ideas, so that our growing knowledge of viral infections will help produce better approaches to control them. Luis M. de la Maza Irvine, California Ellena M. Peterson March, 1991 v ACKNO~EDGEMENTS It would be impossible to single out all those individuals who helped us make this Symposium a reality, however, we would like to take this oppor tunity to express our appreciation for their efforts.

Blastomycosis remains the most enigmatic of human mycotic infections. The enigmas encompass the natural habitat of the etiologic agent, extent of exposure and subclinical infections in endemic areas, distribution of en demic foci throughout the world, inconsistency of serologic evaluation of infected patients, and varying response of such patients to standard treat ment regimens. In spite of diligent investigations by many competent investigators, we still do not know the ecological niche inhabited by the etiologic agent. We have many tantalizing clues but no definite answers. Nor do we know the extent of the endemic areas in the world for this disease. Skin testing, so useful in defining the distribution of histoplasmosis and coccidioidomycosis, has been of no value in mapping endemic areas for blastomycosis. Even the serologic evaluation of known cases of the disease has been too erratic in results to be useful as a diagnostic or prognostic procedure. The enigmas of blastomycosis go straight to the disease itself. There is an extensive literature on the debate concerning the presence and extent of subclinical infections. Case report series demonstrate that such transient infections do occur but, unlike other mycoses, the extent to which this phe nomenon is common in the general population still cannot be assessed. Even the diagnosis of established disease is a major clinical problem.

Integrating Population Outcomes, Biological Mechanisms and Research Methods in the Study of Human Milk and Lactation is the product of the 10th Conference of the International Society for Research on Human Milk and Lactation, held on September 15-19, 2000, in Tucson, Arizona. The presented sessions at the meeting are as diverse as the volume itself. These sessions include the impact of micronutrient deficiencies during lactation on maternal and infant health, the premature infant, developmental immunology, breastfeeding in the industrialized world, and viral transmission in milk. Whenever possible, the sessions were organized to include human population research, research showing the biological underpinnings of the effects on human health, and important methodological issues. This volume is a contemporary and influential tool for human milk biologists, breastfeeding epidemiologists, biochemists, immunologists, clinical specialists, and all professionals and researchers in the field.

Christiaan Eijkman received the Nobel prize for Medicine in 1929 for his discovery that beri-beri is a vitamin-deficiency disease. He had conducted his seminal research on the disease in the fonner Dutch East Indies between 1886 and 1898 at the location of. the present Eijkman Institute for Molecular Biology in Jakarta. In 1998, the first International Eijkman Symposium was held in The Hague, The Netherlands, to celebrate the fact that exactly 100 years earlier Christiaan Eijkman was inaugurated as full professor in Hygiene and Bacteriology at Utrecht University, The Netherlands. The Eijkman-Winkler Centre for Microbiology, Infectious Diseases and Inflammation is the direct descendant of Eijkman's department in Utrecht. vii Contributing Authors Bacbti Alisjabbana Department of Internal Medicine Padjadjaran University (UNP AD) Dr Hasan Sadikin General Hospital Bandung Indonesia Kevin Baird US Navy Medical Research Unit-2 J1. Percetakan Negara 29 Jakarta 15650 Indonesia Phone: +62-21-421-4457 Fax: +62-214244507 Jan P . B. van den Berg Nederland-Batam Foundation Stationsweg 56 6711 PT Ede The Netherlands Phone: +31-318610368 Fax: +31-318612476 Greet J. Boland Eijkman-Winkler Centre University Medical Centre Utrecht ix x Contributing Authors P. O. Box 85500 3584 CX Utrecht The Netherlands Phone: +31-302506536 Fax: +31-302541770 G J . Boland@azu. n1 Graham V. Brown Department of Medicine University of Melbourne Royal Melbourne Hospital Victoria Australia gvb@unimelb. edu. au Frank E. J. Coenjaerts Eijkman-Winkler Centre University Medical Centre Utrecht P. O. Box 85500 3584 CX Utrecht The Netherlands Phone: +31-302507637 Fax: +31-302541770 . EJ . Coenjaerts@lab. azu.

The immune system has evolved in large part to enable organisms to resist microbial infeetion. Given this very fundamental relationship between the immune system and infeetious microbial agents it is entirely appropriate that avolume in this series should be devoted to the immunology of infeetion. Mieroorganisms have long been used as experimental tools by immunologists, and the study of the immune response to viruses and baeteria has eontributed mueh to our understanding of basie immunologieal meehanisms (for example of the meehanism by whieh non-self determinants on eells are reeognized). However there are of eourse important praetieal and elinical reasons for attempting to understand the immunology of infeetions - these inelude the needs for rational design of vaeeines and to understand the pathogenesis of human infeetious diseases. The last deeade or so has seen a resurgenee of interest in infeetious diseases and a reeognition that they remain of importanee and pertinenee to all areas of medicineo This is not just beeause of the advent of AIDS, although that has been a major faetor - the rise in drug-resistant myeobaeterial infeetions and the reeognition of the infeetious aetiology of peptie uleer disease are other illustrations. It should be made elear that this volume deals with aspeets of the immunolgy of baeteria, viruses and fungi - but it does not deal with parasite immunology which it is planned to eover in a separate volume in the series.

Antibodies are crucial to the fine specificity of the immune system. An effective functioning of these molecules requires interaction with immune cells. Receptors for antibodies, Fc receptors, provide this critical link between the humoral and cellular branches of the immune system. This book presents a comprehensive overview of the different Fc receptors currently recognized. The first part of the book contains state-of-the-art overviews on the biological role of FcR. The latest information on FcR heterogeneity, FcR physiology, FcR-ligand recognition, their crucial coordinating role in immunity, interactions with other immunoreceptors, and the role of FcR in immunoglobulin transport and catabolism are discussed. The clinical importance of FcR is developed in the second part of the book. The well-recognized roles of FcR in allergy, inflammation, infectious diseases, autoimmune disorders, and immunotherapeutic importance are reviewed. The information in this book is easily accessible and should be helpful for researchers and clinical specialists as a convenient overview of the field, as well as a comprehensive introduction for students starting in this area of research.

Hot Topics in Infection and Immunity in Children brings together leading experts in the field to provide a current and authoritative view concerning the hottest topics of concern to clinicians caring for children with infections and research scientists working in the areas of infectious disease, immunology, microbiology and public health. The book is based on a collection of manuscripts from a faculty of authors of international standing who contributed to a course in Paediatric Infection and Immunity in Oxford, UK in June 2003.

Scientists and clinicians attending the last "New Directions in Antiviral Therapy" conference in late 1994 could hardly have predicted the revolution in the management of patients with HIV infection that has occurred since. Two new classes of antiretrovirals have been licensed, the second-site RT inhibitors and the protease inhibitors; the long in cubation period of active HIV infection, when the infection is clinically latent, is now un derstood to be a period of intense viral replication and turnover of CD4 lymphocytes; measurements of HI V RNA concentration in plasma have been shown to be essential tools for monitoring the course of HIV infection, deciding when to treat, and assessing the re sults of treatment; and finally, combinations of antiretrovirals, particularly combinations including protease inhibitors, have been shown to have dramatically beneficial effects on patients with HIV infection. These advances, coupled with new drugs for the management of herpesvirus infections, have made dramatic differences in the quality and length of life of HIV-infected patients. Additional advances have been made since 1994 in the prevention or management of influenza virus (zanamavir), respiratory syncytial virus (palvizumab), hepatitis B virus (lamivudine and famciclovir), and enterovirus infections (pleconaril). It is difficult to re member that only slightly more than a decade ago there were only a handful of antiviral agents available (none of which were antiretrovirals), and a number of those were either highly toxic, of dubious efficacy, or both."

The term "autoimmunity" has been used to categorize a number of different diseases of unknown etiology. The term as applied to many of these diseases would probably be interpreted best as "autoreactivity," as the clinical phenotypes are often characterized by an inflammatory-like accumulation of activated cells of the immune system at sites of obvious damage of normal cells and/or tissue. The reasons as to why an immune system should attack itself are far from clear, although the association with specific infectious diseases in genetically susceptible people remains perhaps our best lead. The input of the biotechnological revolution has enabled us to attempt to readdress many of the fundamental questions raised by clinical and serological associations with autoimmune disease. The ability to dissect the immune response to these infectious agents which are associated with autoimmune features (as well as the facility to identify new agents, e. g. HIV), in addition to the ability to clone and sequence immune response genes, has enabled a much better understanding, at least of the complexity of "autoimmunity" to be gleaned. This volume contains the chapters that summarize the plenary presentations given at The Impact of Biotechnology on AUTOIMMUNI1Y meeting in Florence, Italy in June 1993. They cover all aspects from pathogenesis to treatment. The association with infectious diseases and autoimmunity is comprehensively covered by David Isenberg who reviews major issues, such as the association of autoantibodies appearing after infectious disease and antibacterial antibodies associated with autoimmune disease.

Biomaterials associated infection (BAI) is one of the most common complications associated with implantation of any biomaterial regardless of form or function. These infections usually involve bacterial colonization and biofilm formation on the biomaterial itself, rendering the infection impervious to antimicrobials and host defenses. In addition, it is becoming increasingly clear that infection of the surrounding tissues also plays an important role in BAI, and that the infection may be influenced by the composition and design of the implanted biomaterial. In this book, worldwide leaders in the field address this critical problem in the translation of biomaterials research into clinical practice. The book begins with an emphasis on the latest research in the pathogenesis of BAI from microbiological, immunological, and materials science perspectives. The current state of the art in antimicrobial activation of biomaterials through surface modification and the incorporation of antimicrobial agents is then discussed. In the concluding chapters, successful translation of a selection of antimicrobial technologies from preclinical research into clinical use is described alongside a discussion of the utility of these devices and perspectives for future development. This book is essential reading for researchers and clinicians who are interested in understanding the fundamentals of BAI, the latest in antimicrobial materials research, and the state of the art in clinically available antimicrobial containing medical devices.

It is now 10 years since the first AIDS cases were reported in the USA. In that relatively short period of time, study of the disease has moved from the level of early clinical description to exhaustive and extensive laboratory characterization of the human immunodeficiency virus (HIV), the immune responses directed towards it and reasons for their failure. This volume provides contributions from clinical and basic scientists who are actively involved in research in a number of areas of current interest and controversy. Further progress in the clinical management of the HIV-infected patient will undoubtedly build on the basic knowledge about HIV and its modes of pathogenesis. The intimate relationship between HIV and the human immune system provides observations and questions that are relevant to viral immunopathogenesis in general. In the first chapter the clinical features of HIV immunodeficiency are re viewed, and aspects of its changing face are discussed. Dr Tersmette then presents evidence for changing viral characteristics at different stages of the disease. This view of close competition for ascendancy between HIV and the host immune response raises questions about current approaches to therapy."

Now that Helicobacter pylori is generally accepted as a key aetiological agent in gastric cancer as well as the main agent in peptic ulcer, it can claim to be the most important new discovery in clinical gastroenterology of the last decade, and yet there is no up-to-date book available on the subject that is designed primarily for the clinical gastroenterologist. This book aims to fill that niche. It should also be of interest to the basic scientist, to those providing a clinical laboratory service (microbiologists and histopathologists), and to epidemiologists and others involved in clinical research.

Over the past ten years, many powerful new techniques have been developed that have dramatically changed malaria research. The second edition of" Malaria: Methods and Protocols" expands upon the previous edition with current, detailed techniques for laboratory research. With new chapters on parasite culture techniques, genome manipulation methods, 'omic' approaches, and techniques for studying the biology of the red blood cell and pre-erythrocytic stages of" Plasmodium." Written in the highly successful" Methods in Molecular Biology " series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls.

Authoritative and practical, "Malaria: Methods and Protocols, Second Edition," offers a comprehensive set of standard techniques for laboratory researchers."

The preparation of Aging, Immunity, and Infection has been a "labor of labor. " When we began, there existed a huge literature-but manage able, we thought, given our years of experience in the area often referred to as immunogerontology. However, in the time that we have been at work, the new relevant literature has increased at a prodigious rate. The more we read and tried to assimilate, the farther we fell behind. In order to have any hope of completing a book on this rapidly evolving topic, we have been forced to become increasingly selective in covering new and re cent publications. We dare to hope that many read ers will find the book useful and only a few will dweIl on the inevitable inadequacies. We consider the book a work in progress, and welcome suggestions for future editions. Five chapters cover several aspects of infection and the decline of immunity with age. The first chapter "Human Aging: Present and Future," is devoted to demographics and theories of senescence. Chap ter 2 outlines the gradual breakdown of resistance to infection in the aged individual. Chapters 3 and 4 cover changes in innate and acquired immunity. The final chapter, "Nutrition, Longevity, and Integrity of the Immune System," discusses such provocative ideas as life-span exten sion and nutritional intervention for the delay of immunosenescence.

For bacteria ..."the times are achanging..". The genomes of over 60 different bacteria have now been sequenced, and we know a lot about the important research organism Escherichia coli, the important industrial organism Bacillus subtilis, and about important plant and human pathogens. It will not take long before we know all the gene products and their functions of a few of these bacteria. Some of us already begin to think about a digital model E. coli or Bacillus cell. For that end we need to know all the physiological activities and metabolic routes of the cell. But in addition we like to know how things work at the molecular level and how protein and membranes as well as other (macromolecular) structures work together to carry out specific cell functions.

Protein Secretion Pathways in Bacteria describes all the known folding and targeting routes of inner and outer membrane proteins as well as of proteins that are secreted by several specific export routes. The book gives detailed molecular information about the structures that are important for the different mechanisms involved. This is a valuable contribution to the understanding of how rather simple and yet complex bacterial cells work.

This completely updated fifth edition of Bacterial Fish Pathogens is a comprehensive discussion of the biological aspects of the bacteria which cause disease in farmed and wild fish. Since the 4th edition was published in 2007, there has been an upturn in the application of molecular approaches to taxonomy, diagnosis and vaccine development. New pathogens, e.g. Aeromonas schubertii, have been described. Also, there has been the emergence of diseases caused by bacteria which have not been cultured, and which have been equated with new taxa, i.e. Candidatus . Consideration is given to all the bacterial fish pathogens, including primary pathogens and opportunists."

Mathematical epidemiology of infectious diseases usually involves describing the flow of individuals between mutually exclusive infection states. One of the key parameters describing the transition from the susceptible to the infected class is the hazard of infection, often referred to as the force of infection. The force of infection reflects the degree of contact with potential for transmission between infected and susceptible individuals. The mathematical relation between the force of infection and effective contact patterns is generally assumed to be subjected to the mass action principle, which yields the necessary information to estimate the basic reproduction number, another key parameter in infectious disease epidemiology. It is within this context that the Center for Statistics (CenStat, I-Biostat, Hasselt University) and the Centre for the Evaluation of Vaccination and the Centre for Health Economic Research and Modelling Infectious Diseases (CEV, CHERMID, Vaccine and Infectious Disease Institute, University of Antwerp) have collaborated over the past 15 years. This book demonstrates the past and current research activities of these institutes and can be considered to be a milestone in this collaboration. This book is focused on the application of modern statistical methods and models to estimate infectious disease parameters. We want to provide the readers with software guidance, such as R packages, and with data, as far as they can be made publicly available.

Endotoxins are potentially toxic compounds produced by Gram-negative bacteria including some pathogens. Unlike exotoxins, which are secreted in soluble form by live bacteria, endotoxins are comprised of structural components of bacteria. Endotoxins can cause a whole-body inflammatory state, sepsis, leading to low blood pressure, multiple organ dysfunction syndrome and death. This book brings together contributions from researchers in the forefront of these subjects. It is divided into two sections. The first deals with how endotoxins are synthesized and end up on the bacterial surface. The second discussed how endotoxins activate TLR4 and, in turn, how TLR4 generates the molecular signals leading to infectious and inflammatory diseases. The way endotoxins interact with the host cells is fundamental to understanding the mechanism of sepsis, and recent research on these aspects of endotoxins has served to illuminate previously undescribed functions of the innate immune system. This volume presents a description of endotoxins according to their genetic constitution, structure, function and mode of interaction with host cells.