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Viral Infections and Treatment

2003 Edition, August 26, 2003

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Active, Most Current

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ISBN: 978-0-8247-4247-8
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Product Details:

  • Revision: 2003 Edition, August 26, 2003
  • Published Date: August 26, 2003
  • Status: Active, Most Current
  • Document Language: English
  • Published By: CRC Press (CRC)
  • Page Count: 769
  • ANSI Approved: No
  • DoD Adopted: No

Description / Abstract:


The obliteration of diseases that impinge on our health is a regal yardstick of civilization's success, and those who accomplish that task will be among the true navigators of a brave new world.

Viruses are regarded by some as thieves, parasites, and murderers. Others regard them as the ultimate examples of informational nanotechnology. This book is concerned with the dark side of viruses and the diseases they cause. However, it should not be forgotten that it is because viruses are so technologically advanced that we have been able to make so much progress in our understanding of genetics, cell biology, biochemistry, and molecular biology. Paradoxically, the knowledge given us by the study of viruses has also led to the discovery of many antiviral compounds.

Viral infections have long been regarded as untreatable. In the middle of the last century, the science of virology was in its infancy and viral chemotherapy was but a gleam in the eye of leading microbiologists like Robert Doerr, who fervently believed in the existence of chemotherapeutic agents that would be effective against a large number of varius-related diseases [1]. However, the realization that viruses usurped the metabolic machinery of the cell raised the intellectual barrier that a ‘‘virotoxic'' agent would also be toxic toward the normal cell. Thus, therapeutic nihilism became an accepted philosophy within the majority of medical circles.

Successful control of some viral diseases came about only through the advent of prophylactic vaccination for now nearly extinct viruses such as smallpox and polio. Unfortunately, not all viral diseases lend themselves to vaccination. For example, researchers have tried for decades to develop vaccines against herpes simplex viruses but without much success. At the turn of the new millennium, a glimmer of understanding emerged as to why previous attempts had failed: herpesviruses have evolved strategies to interact with the mechanisms that alarm the immune system and inactivate or divert the signals. Similarly, major efforts to develop a vaccine against human immunodeficiency virus have thus far failed to reach their target, partly because of the enormous genetic drift of the virus and partly because of the lack of knowledge about the immune reactions that have to be triggered in order to create an effective vaccine against a virus that attacks and modulates the immune system itself. Therefore, although our understanding of immune mechanisms in the fight against viruses is increasing, some viruses may never be controlled by vaccines but will almost certainly require the development of low-molecular-weight antiviral compounds or novel immunomodulating principles before they succumb.

A major conceptual breakthrough in chemotherapy occurred in the late 1940s when Hitchings and Elion realized that the rate of nucleic acid synthesis in infected tissues is much higher than that of the normal host tissue. This led to the idea of antimetabolite chemotherapy for cancer and parasitic diseases that ultimately led to antiviral agents such as iododeoxyuridine, deoxycytidine, hydroxyethoxymethylguanine, and azidothymidine. The latter two are better known as acyclovir and AZT, respectively. Although a thiosemicarbazone derivative was the first lowmolecular- weight antiviral compound used in humans—as a prophylactic treatment for smallpox contacts in the early 1960s [2]—herpesvirus disease was the first viral infection for which a truly efficient treatment was developed, in the form of acyclovir. When AIDS was recognized as a viral disease in the early 1980s, treatment at first seemed unlikely if not impossible. However, only four years after the virus had been discovered, the first drug, azidothymidine, had been introduced onto the market. We now have several antiviral drugs in our arsenal, and not all are antimetabolites: two novel drugs against influenza have been developed that interact with, and inhibit, the viral neuraminidase, whereas the viral protease and reverse transcriptase of HIV are principal targets for current treatments with non-nucleosidic inhibitors. Some of the nucleoside analogs developed for HIV therapy have been found to be effective against hepatitis B as well. Ribavirin, in combination with interferon, has also been successfully introduced for the treatment of hepatitis C and can be regarded as an effective immunomodulatory principle.

Daunting as it seemed for years, in the year 2003 effective drug therapy does exist for a variety of viral diseases, just as Doerr and colleagues predicted 60 years ago. Concomitant with this, we have also witnessed the development of a new era of diagnostic tools. Polymerase chain reactions combined with appropriate methods for sequence detection now allow not only the diagnosis of a viral disease but also the determination of a viral subtype. In addition, methods that allow the quantification of the virus in body fluids or tissues in order to determine viral loads are now standard in clinical trials, and drugs are being approved on the basis of showing efficacy in reducing this particular parameter. Thus, the demonstration of efficacy of an antiviral drug no longer depends entirely on clinical endpoints once a relationship has been established between the reduction in viral load and resolution of clinical signs has been established.

All these advances in understanding and treating viral diseases are relatively recent developments and are proceeding at a rapid pace. Thus there is often a gap in knowledge about the diagnostic and therapeutic options currently available for clinical management. It is our hope that this book will fill that gap, and we have tried to present in a practical and cohesive manner all the latest developments and their use.

The introductory chapter gives an overview of the most important human viral pathogens and their transmission as well as emerging viral pathogens. At the time of writing, severe acute respiratory syndrome (SARS) dominates the media; it is an example of the unpredictability of emerging viral diseases and illustrates the potential for explosive dissemination of viruses throughout our global community. Not only does the novelty of the SARS-associated virus make it difficult to assess the long-term significance of the outbreak, but also the SARS epidemic itself exposes the desperate need for rapid diagnosis and reporting of unusual outbreaks and for international cooperation in investigating such occurrences.

The main structure of this book consists of specific sections on infections of the respiratory tract, the skin and mucosa, and the liver as well as special sections on human immunodeficiency virus and on herpesvirus infections of the immunocompromised host. We have included chapters on what are currently regarded as the most clinically relevant viruses—influenza viruses, respiratory syncytial virus, rhinovirus, the herpes simplex viruses, varicella zoster virus, papillomaviruses, hepatitis viruses, human immunodeficiency virus, human cytomegalovirus, Epstein-Barr virus, and the recently identified human herpesviruses 6, 7, and 8. Each chapter describes the respective diagnostic measures guiding therapy, approved therapeutic agents, their mode of action, and their clinical applications.

This book is intended not only for infectious-disease physicians and virologists who want to update their knowledge on transmission, diagnosis, and treatment of viral diseases but also for the nonspecialist who wishes to obtain a greater understanding of the clinically important viral pathogens. It is clear that there is still a less than complete understanding in the community of the burden of mortality and morbidity caused by viruses. HIV continues to devastate the world population and now ranks equal to tuberculosis as a global killer. The spread of the virus is still exponential in many areas of the world, and a constant 35,000–40,000 people are being newly infected in both the United States and Europe each year. Persistent viral infections develop unusual patterns of disease and unusual severity under conditions of immunosuppression by HIV, be it herpesvirus, cytomegalovirus, or papillomaviruses. Similarly, many of the viruses discussed in this book cause considerable, even life-threatening, problems in immunocompromised states after transplantation or in neonates. Therein lies the reason for our putting this book together, and it is our profound hope that it will serve the reader well. We hope that it will be a constant companion for physician, student, and layperson alike

We are grateful to everyone who has accompanied us on the sometimes tortuous path of producing this volume, especially the contributors and the editorial staff of Marcel Dekker, Inc