This book is the outcome of an international conference, held at the Aviya Sonesta Hotel in Eilat, Israel, on March 24-27, 1985. This was the 30th in a series of the annual OHOLO Conferences, sponsored by the Israel Institute for Biological Research. Participants in this Conference consisted of scientists from four teen countries; represented a broad spectrum of research interests; and included a well-balanced representation from academia, clinical institutions and pharmaceutical industry. The book includes talks, poster sessions, and a comprehensive general discussion, all from the proceedings of this conference. In the interest of assuring a rapid publication of the novel infor mation reviewed, this book has been prepared in camera-ready format. We are cognizant of the fact that several typographical errors may exist in the text, and that there are variations in style and typeface of the var ious chapters. This, we felt, was a reasonable compromise for the sake of speed and efficient transmission of valuable scientific information. No body is perfect . **** The success of the conference, and hence the quality of this book are attributable to the extensive efforts of a large number of extremely capable individuals. These include members of the Scientific Organizing Committee, and the Technical staff of the OHOLO Organization. Of course, the conference could not have succeeded without the high quality of the presentations, and the enthusiastic participation of the contributing scientists.

Infectious diseases remain a major problem for physicians and other health professionals dealing with problems of the reproductive system. Accordingly, this two-volume comprehensive presentation of infectious diseases involving the male and female reproductive systems promises to be a major contribution in this field and to fill a much-needed vacuum. During the past three decades, the introduction of antimicrobial therapy has dramatically altered both the clinical presentation and the therapeutic approaches employed in dealing with the traditional infections of the repro ductive system. In addition, the changing demographics of infectious problems in the industrial countries and the developing world have been a source of concern. A good deal of important information on this topic is included in this series. In recent years, considerable attention has been given to the role of Myco plasma and Chlamydia in both male and female infertility and the problems related to genital herpes and human papilloma virus infections. Current clinical information is included on these infections as well as on newer aspects of diagnosis, such as the use of laparoscopy in the diagnosis and treatment of pelvic inflammatory disease. Also addressed is new information regarding the role of actinomycosis in pelvic infections; current problems such as toxic shock syndrome and acquired immune deficiency syndrome (AIDS) are reviewed as well. New concepts are included in these volumes to complement the clinical information. The attachment of microbial organisms to sperm may help to explain access of these and other organisms to the upper female genital tract."

For centuries the great minds of medical science puzzled over the importance of the cerebrospinal fluid. As far back as Hippocrates, it was thought that this "phlegm" that flooded the intracranial contents had pathological significance. However, not until the late 1800s, when Quincke introduced and popularized lumbar puncture, did physicians take an interest in the study of this fluid in relation to clinical illness. Since then a variety of techniques for obtaining cerebrospinal fluid from various sites have developed, and the relationship of cerebrospinal fluid to a variety of disease processes has received considerable study. In this volume, we have attempted to assemble reviews of some of these important developments during the past century. Chapter 1 contains a historical review of key investigations that helped shape our concepts of cerebrospinal fluid from the earliest recorded description by the author of the Edwin Smith Surgical Papyrus in the seventeenth century B. C. to contemporaries such as Kabat, Glusman, and Knaub, who introduced quantitative determinations of cerebrospinal fluid gamma globulin levels. In Chapter 2 there is a description of our current understanding of the anatomical compartment for the cerebrospinal fluid and the physiology of its formation, circulation, and absorption. Dr. Richard Leech in Chapter 3 contributes a comprehensive description of the disorders associated with excessive quanti ties of cerebrospinal fluid-commonly referred to as hydrocephalus. A variety of techniques for properly collecting and evaluating cerebrospinal fluid are detailed in Chapter 4."

This volume represents the Proceedings of the Symposium on AIDS, Drugs of Abuse and the Neuroimmune Axis. This meeting was held in San Diego, California, November 11-13, 1995. As in the previous symposia in this series, productive studies were reviewed concerning the relationship between the nervous and the immune systems in regards to the relationship between drugs of abuse and infections, especially infections by the immunode ficiency virus that causes AIDS. In recent years, various investigators have begun to describe the role of illicit drugs and their endogenous counterparts on the brain-immune axis. It is widely recognized that the neuroendocrine system is intimately involved in the effects and manifestations of the interactions of drugs of abuse and the immune system. The meeting on which the chapters in this book are based brought together many biological scientists from an array of various scientific disciplines whose work is focused on the effects of drugs of abuse on the neuroendocrine-immune axis and its relationships to immunodeficiency caused by the AIDS virus. As in the past, the symposium was unique in focusing on the . brain-immune axis from the viewpoint of drugs of abuse rather than from the viewpoint of immunity or the brain itself."

Although there have been many books on HIV and AIDS, surprisingly little has been published that focuses on the immunology of retroviral infections in general, and HIV in particular. Retroviral Immunology: Immune Response and Restoration is the first book of its kind to address the most important aspects of the immunology of retroviruses, including not only the virus-specific immune responses, but also genetic and virologic factors modulating these responses. The book also deals directly with the emerging concept of immune restora tion in retroviral infections, a particularly important subject to the thousands of clinicians who deal with this problem on a daily basis. With the advent of highly effective antiviral drug regimens to slow down the replication of HIV and the progression of AIDS, new challenges and opportunities are arising. Restoration of general immune function has brought with it not only complica tions of immune restoration-mediated disease, but also the realistic hope for meaningful restoration of the ability to control HIV replication with the immune system. Leading scientists in the field have summarized the most current informa tion regarding experimental and clinical aspects of retroviral infections. Retroviral Immunology: Immune Response and Restoration should prove an impor tant point of reference for basic scientists and clinicians in this area of research. We are indebted to all of our authors for their excellent contributions."

The emergence of pathogens resistant to conventional antimicrobial agents has forced us to intensify the efforts in search for new approaches to prevent infectious diseases. Such a direction was indicated in studies over the last two decades showing that adhesion of pathogens, primarily via glycoconjugate or protein receptors of the host tissue, is crucial for the infectious process. Moreover, it was found that infection can be prevented by blocking adhesion of the pathogen to mucosal surfaces of the host. The various aspects of interference with the process of microbial adhesion as a way of preventing diseases were the subject of the Bat-Sheva Seminar, "Towards Anti-Adhesion Therapy of Microbial Infectious Diseases," held in Zichron Yaakov, Israel, February 25 to March I, 1996. A major aim of the Bat-Sheva de Rothschild Foundation for the Advancement of Science in Israel, which sponsors a series of seminars, ours among them, is to provide the necessary tools and settings for international forums and exposure of young scientists and promising students to the state of the art of the field. This goal has been achieved during the week's discussions, and its major aspects are presented in this compendium. The seminar's participants, as well as the readers of this book, thank the founder and Foundation for their support. This book includes the major themes of this rapidly growing area. However, by no means do we intend to cover every bit and piece in it. The book's first section deals with the lectin-sugar interactions and their inhibitors.

When Pascal James Imperato, MD, assumed the edi * Exclusion by the New York State Departm~nt of Health of qualified laboratories from HIV testmg torship of the New York State Journal of Medicine in 198~, the acquired immunodeficiency syndro. me (AIDS) epI * Protection of health care workers * Responsibilities of physicians and other health care demic in the United States was already SIX years old. Dur ing the time of his editorship, two thematic issues of the workers Journal have been devoted to AIDS. In addition, a large * Public education number of original communications have been regularly * AIDS confidentiality published on the subje~t. This volume ?rings together The Symposium on AIDS in Washington, DC, had important articles published on AIDS m the Journal been so successful that the MSSNY, under the auspices of during 1987 and 1988. . . the task force and the Division of Governmental Affairs, In the early years of the epidemic the Medical Society of held two informational symposia for state senators and the State of New York (MSSNY) was aware that it had a assemblymen and their staffs in Albany, New York. Thes. e responsibility to both the professi?~ an~ the public to add were presented in February 1988 and. March. 1989. ,!,hIS its efforts to those already mobIlized m the attempt to effort has convinced the MSSNY that It has given legisla understand and control this tragic disease. Early on, the tors a better understanding of the overall AIDS problem.

During the past two decades, virus taxonomy has advanced to the point where most viruses can be classified as belonging to families, genera, or groups of related viruses. Virus classification is primarily based on chem ical and physical similarities, such as the size and shape of the virion, the nature of the genomic nucleic acid, the number and function of com ponent proteins, the presence of lipids and of additional structural fea tures, such as envelopes, and serological interrelationships. The families, genera, or groups of viruses that have been defined on the basis of such criteria by the International Committee on Taxonomy of Viruses (ICTV) will be described in some detail in this catalogue and illustrated by elec tron micrographs. In my present attempt to list most if not all well es tablished and studied viruses in alphabetical order, I have largely confined myself to identifying them only in such taxonomic terms, generally without quoting specific data reported for individual viruses. If the latter data do not at times agree closely with those given for the taxon or group, it is difficult to decide to what extent this is attributable to misclassi fication due to insufficient data and errors in the analytical procedures and descriptions, or to what extent this is an expression of Nature's free dom of choice and abhorrence of restrictive classifications."

The first book was on "Theory and Practice" of antibiotic stewardship in its broadest sense -the how to do it and the do's and don'ts. The second, on "Controlling resistance" was very much on the relationships between use and resistance and beginning to home in on the hospital as the main generator of resistance, but mainly looking at it from a disease/clinical perspective. The last 3 chapters on MRSA, ended where the 3rd book will take off. "Controlling HAI " will concentrate on specific MDR organisms highlighting their roles in the current pandemic of HAI and emphasizing that the big issue is not so much infection control but antibiotic control, in the same way that antibiotic over-reliance/ over-use has caused the problem in the first place. Up 'till now the emphasis for controlling MRSA, C diff and all the other MDROs has very much been on IC, which clearly isn't working. This book will gather all the evidence for the increasingly popular view that much more must be done in the area of antibiotic policies/ stewardship, especially when we are in danger of a "post antibiotic" era, due to a real shortage of new agents in the pipeline.

Protecting Infants through Human Milk: Advancing the Scientific Evidence provides a forum in which basic scientists, clinicians, epidemiologists, and policy makers exchange the latest findings regarding the effects of human milk and breastfeeding on infant and maternal health, thereby fostering new and promising collaborations. This volume also integrates data from animal and in vitro laboratory studies with clinical and population studies to examine human milk production and composition, the mechanisms of infant protection and/or risk from human milk feeding, and proposed interventions related to infant feeding practices. Additionally, it stimulates critical evaluation of, and advances in, the scientific evidence base and research methods, and identifies the research priorities in various areas.

A great truth is a truth whose opposite. is also a great truth. Thomas Mann (Essay on Freud, 1937) This volume centers on pseudorabies (PR V), herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), and human cytomegalovirus (CMV) and fulfills three objectives. The chapters on the epidemiology and latency of HSV, and on the glycoproteins specified by HSV and CMV, set the stage for the discussions of the immunobiology and pathogenesis of human herpesvirus infections in Volume 4. The epidemiology of HSV is the basis of our understanding of the spread and survival of this virus in the human populations. Central to the epidemiology of HSV and its pathogenesis in humans is the ability of the virus to remain in a latent state for the life of its host. The viral membrane glycoproteins are among the most interesting virion proteins, primarily because of their critical role in the initiation of infection. Since they are the surface membrane proteins of the virion and appear on the surface of productively infected cells, they are also the obvious if not the exclusive targets of the immune response. The chapters on the transforming potential of HSV and CMV, and on the role of HSV in human cancer, deal with challenging problems requiring rather different experimental tools.

The past decade has witnessed a burst of activity and interest in the discovery and design of drugs that cleave DNA and RNA with sequence specificity. This interest stems from the potential of this class of compounds to be useful as therapeutics agents, in particular in the field of the treatment of cancer and viral diseases. Further, a side benefit of such studies is the discovery of novel mechanisms and uses of such agents as tools in the study of structure and function of nucleic acids. Up to now, no international meeting has been organized to recognize the immense progress that has been made in this field. The field of DNA and RNA cleavage by natural and chemical drugs now includes researchers working with rather dissimilar agents but with common underlying mechanisms of DNA damage. Until recently, these scientists were working in separate, apparently unrelated areas, such as the enediyne antibiotics and their synthetic analogues, bleomycin-metal complexes, metal-drug complexes, ribozymes and ribozyme mimics, and antisense and antigene oligonucleotides, etc. It is now clear that these research areas have in common strategies and targets. Researchers representing these areas worked together at this workshop where these common interests were discussed and scientific ideas modified and criticized. Such a workshop should lead to new research approaches and collaborative interactions, and is expected to significantly enhance the progress in the field of DNA and RNA cleavage.

The World Health Organization estimates that at least five million people worldwide are infected with human immunodeficiency virus (HIV) Of these about 100,000 are in Asia and Oceania, 500,000 in Europe, 2 million in the Americas and 2.5 million in Africa (Mann, 1989). The acquired immunodeficiency syndrome is characterized by a derangement in cell-mediated immunity leading to opportunistic infections with for example Mycobacterium spp., Candida spp., Cryptococcus neoformans, Pneumocystis carinii, Toxoplasma gondii and Cryptosporidium. The third symposium on "Topics in Mycology" brought together 265 experts from 32 countries to discuss the epidemiology, immmunological and pathogenetic aspects of AIDS and its opportunistic infections in general and fungal infections in particular. Pneumocystis carinii pneumonia is by far the commonest opportunistic infection in AIDS patients. The nature and classification of P. carinii is still controversial. In search for its true taxonomic affinities an introductory paper formulates a number of key questions. Candidosis is another frequent opportunistic infection. A number of papers discuss the possibility that selective pressures may operate on Candida albicans within the AIDS population and influence its nature: this might have an impact on prophylaxis and curative and/or suppressive therapy.

Upon infection the host needs to mount vigorous immune response against pathogen in order to successfully control its replication. However, once the infectious agent is controlled or eliminated, host cells need to signal the immune system to slow or cease its activities. While vast knowledge has been accumulated through the years on the mechanisms involved in the initiation and effector phases of the immune responses, the pathways triggered in order to modulate or end innate and acquired immunity are becoming more evident as evidence for its relevance comes to surface. Due to its biological power, evidence has surfaced indicating that eventually pathogens may take advantage of such regulatory pathways in order to escape effector mechanisms and progress to persistence. This book will discuss several cellular pathways involved in controlling immune response in the context of infectious diseases, their biological consequences and potential "hijack" of these pathways for the benefit of pathogen leading towards pathogen persistence as opposed to clearance.

During recent decades, it has been firmly documented that chlamydiae are com mon and important pathogens in humans and animals. In humans, chlamydiae are known to cause trachoma (which is still one of the major blinding diseases in the world) and are also one of the most common etiological agents of sexually transmitted diseases and the sequelae thereof, such as infertility. In the last few years, it has also become evident that chlamydiae, i.e., the so-called TWAR agents, are common respiratory tract pathogens. Chlamydiae are also important pathogens in birds and lower mammals, in whom they cause a variety of infectious conditions, a spectrum which has in creased every year. Some of these infections occur as zoonoses, e.g., psit tacosis/ornithosis and, as recently discovered, abortion. Know ledge of the molecular biology and immunobiology of chlamydiae has expanded rapidly during recent years. Insight into the pathophysiology of chla mydial infections has also increased, and new methods for the diagnosis of chlamydial infections have been introduced. The importance of establishing control and preventive programs for chla mydial infections has become obvious in order to combat the present chlamydial epidemic. We hope that this book can usefully serve those who want to increase their general knowledge of Chlamydia and that it can act as a handbook and reference source for those involved in chlamydial research as well as for those working with chlamydial infections in medical and veterinary clinical disciplines, includ ing clinical laboratories."

The impact of Helicobacter pylori on basic science and the clinical management of patients with the complications of this infection is bewildering. The explosion of new information both in the laboratory and at the bedside has progressed at an unprecedented rate. Our main objective in furthering this progress has been to integrate this new information and organize a series of top-quality presentations and discussions between investigators and clinicians on all aspects of H. pylori research and to review the current position and future research directions. To that end, the second meeting 'Helicobacter pylori: Basic Mechanisms to Clinical Cure' was organized in June 1996 in Ottawa, Canada, following the successful format of the first such meeting held in Amelia Island, Florida, in 1993. The meeting again focused on all timely aspects of H. pylori research. Internationally renowned basic and clinical scientists, all experts in their respective fields, explored in depth the spectrum of H. pylori infection and the related complications of gastritis, peptic ulcer, gastric cancer and lymphoma.

Influenza continues to be an ongoing problem despite the existence of vaccines and drugs. Disease outbreaks can occur relatively quickly as witnessed with the recent emergence of the influenza virus A/H1N1 pandemic. The development of new anti-influenza drugs is thus a major challenge. This volume describes all aspects of the virus structure and function relevant to infection. The focus is on drug discovery of inhibitors to the enzyme sialidase, which plays a key role in the infectious lifecycle of the virus. Following an overview of the influenza virus, the haemagglutinin, the interactions with the cell receptors and the enzymology of virus sialidase, recent results in drug design are presented. These include a full coverage of the design, synthesis and evaluation of carbohydrate as well as non-carbohydrate influenza virus sialidase inhibitors. Further reviews of the clinical experience with influenza virus sialidase inhibitors and of the development of resistance to these inhibitor drugs complement the topic.

Only in recent years has it been revealed that V. cholerae is a normal inhabitant of esturine and riverine waters. This means that even if the disease can be eliminated from human population by vaccines etc. the vibrio will continue to survive independently in the environment. It is likely that the environment is the source of epidemic strains. This is the first book to focus on the implication of these discoveries.

Despite the major developments in the therapeutic armamentarium for the treatment of infection, the morbidity and mortality of this complication remains very high in patients with compromised defences. Cancer and its treatment represents a major predisposing condition to a variety of infections. These adverse events are still with us, in spite of much progress in the therapy of infectious disease, since cancer therapy is becoming more aggressive, yet further lowering the host's capacity to cope with infections. Moreover, the pathogens adapt effectively to drugs, and at a pace that might outrun industry's capability to produce new agents. Finally, new pathogens are appearing as a consequence of both selection and severe immunosuppression. Infection is so common among cancer patients that its diagnosis and management represent a daily challenge to all oncologists, who must continually strive to keep abreast of developments in the area. The present comprehensive review of the most crucial and challenging aspects of the infectious complications in cancer patients will help them to do just that.

During the last decade or so vaccine development has been facilitated by rapid advances in molecular and cell biology. These have laid the foundations of a new generation of vaccines exemplified by subunit vaccines produced through gene cloning and by synthetic peptides mimicking small regions of proteins on the outer coat of viruses. Such peptide~ are capable of eliciting virus-neutralizing antibodies. Unfortunately, subunit and peptide vaccines are only weakly or non immunogenic in the absence of immunological adjuvants that are known to augment specific cell-mediated immune responses to the antigens and to promote the formation of protective antibodies. This book contains the proceedings of the 4th NATO Advanced Studies Institute (ASI) "Vaccines: New Generation Immunological Adjuvants" held at Cape Sounion Beach, Greece, during 24 June -5 . July 1994 and deals in depth with both theoretical and practical aspects of vaccinology. These include the role of antigen presenting cells in the induction of immune responses. immunopotentiation by a variety of new generation immunological adjuvants and vaccine carriers. and recent advances and perspectives in experimental vaccines as well as vaccinatioll with nucleic acids. We express our appreciation to Dr. K. Dalsgaard and Dr. J. L. Virelizier for their cooperatioll in planning the ASI and to Mrs. Concha Pening for her excellent production of the manuscripts. The ASI was held under the sponsorship of NATO Scientific Affairs Division and generously co-sponsored by SmithKline Beecham Pharmaceuticals (Philadelphia).

Many children admitted to the pediatric intensive care unit (PICU) are admitted with serious infections. If they do not have serious infections prior to admission, there is also a high chance of them acquiring nosocomial infection once admitted. Many syndromes may lead to serious infection and the need for high dependency or intensive care. In addition, the numbers of children who are severely immunocompromised and surviving for extended periods are increasing. Any delay in therapy may produce more severe infection in an immunocompetent patient. As the influence of genetic factors in infectious disease becomes evident and new therapies and new modes of therapy have been introduced, there is the need to draw together these topics into one text. Infectious Diseases in the Pediatric Intensive Care Unit specifically examines infectious disease aspects of pediatric intensive care, from the reasons for admission, the risks of nosocomial infection, infection control, modes of therapy and outcomes.

This volume, now the third in a series, presents a more hetero geneous content than previous issues. It covers two previously rare but now common opportunistic infections in the United States, a common parasitic disease in Japan, exciting but difficult problems in developing a malarial vaccine, a study exemplifying the role of T lymphocytes in parasitic infections, and a fascinating review of the relationship between the schistosomes and their molluscan hosts. The first chapter covers cryptosporidiosis, which has become a household name since the outbreak of the acquired immunodeficien cy syndrome (AIDS). However, infection is now recognized to occur widely in immunocompetent individuals, with clustering of infection among veterinary students, laboratory workers, children in day care centers, and family members. It can also be the cause of traveler's di arrhea and nosocomial infection. Indeed, Cryptosporidium has be come recognized as the leading protozoal cause of diarrhea world wide. This chapter provides a concise, yet comprehensive, review on aspects of epidemiology, microbiology, clinical features, diagnosis, and treatment of this important disease. Recent in vitro studies of Cryptosporidium, conducted in Dr. Flanigan's and other laboratories, are described. They complement the extensive clincial experience of Dr. Soave, who summarizes her many articles in this field. The second chapter describes another common opportunistic infec tion among AIDS patients, toxoplasmosis. This disease differs from cryptosporidiosis in that it was recognized as a common infection in immunocompetent individuals even before the AIDS outbreak."

This volume provides guidance and answers to frequently asked questions in infectious diseases, thus facilitating improved patient care, prudent and cost effective management and investigation of these disorders. Other more complicated but less common conditions are also reviewed. Uniquely, this volume directly discusses several controversies regarding infectious diseases from the 21st century.

The revised and up-to-date third edition of Drug Interactions in Infectious Diseases delivers a text that will enhance your clinical knowledge of the complex mechanisms, risks, and consequences of drug interactions associated with antimicrobials, infection, and inflammation. The third edition features five new chapters that cover material not addressed in previous editions. These new chapters describe interactions with a number of drug classes such as non-HIV antiviral, antimalarial, antiparasitic, antihelmintic, macrolide, azalide and ketolide agents. A novel chapter on probe cocktail studies has been included to highlight an important research tool for drug development. These chapters address material that cannot be retrieved easily in the medical literature. The highly acclaimed food-drug interactions as well as the study design and analysis chapters remain definitive references. The newly written drug-cytokine interaction highlights the need for our improved understanding of the complex interrelationship of acute infection, inflammation, and the risk of drug interactions. Informative tables on specific drug-drug interactions are provided throughout the chapters as a quick clinical resource. The Third Edition of Drug Interactions in Infectious Diseases is a distillation of relevant drug interactions associated with antimicrobials, infection, and inflammation. This concise review of the mechanisms and strategies to manage drug interactions should be valuable to all health care practitioners. Features * Definitive reference source of up-to-date information on antimicrobial drug interactions * Informative tables on the degree of interaction for specific antimicrobial agents * In-depth discussion of mechanisms and potential mechanistic pathways of interaction * New chapters on non-HIV antiviral, antimalarial, antiparasitic, and macrolide, azalide and ketolide agents * New chapter on probe-cocktail studies as a research tool to study drug-drug interactions * Inclusion of new antimicrobial agents and their associated drug interactions * First rate chapters on study design and analysis, and drug-food interactions * A fresh perspective on drug-cytokine interactions * Authoritative chapter on regulatory considerations of drug interactions during drug development

This series of entertaining essays provides a unique insight into some of the key discoveries that have shaped the field of parasitology. Based on interviews with 18 of the world??'s leading parasitologists and epidemiologists, the stories of their contributions to discovery in contemporary parasitology and infectious disease biology are told. Taken together, the essays provide a historical account of the development of the field, serving as a bridge between these discoveries and current research. The book provides a real insight into the thought processes and approaches taken in generating break through scientific discoveries, ranging from immunology to ecology and from malaria and trypanosomiasis to schistosomiasis and Lyme disease. This engaging and lively introduction to discovery in parasitology will be of interest to all those currently working in the field and will also serve to set the scene for future generations of parasitologists.