5TH EDITION
Biological Safety
PRINCIPLES AND PRACTICES
5TH EDITION
Biological Safety
PRINCIPLES AND PRACTICES
EDITED BY
DAWN P. WOOLEY
Wright State University, Dayton, Ohio
KAREN B. BYERS
Dana Farber Cancer Institute, Boston, Massachusetts
Washington, DC
Copyright © 2017 by ASM Press. ASM Press is a registered trademark of the American Society for Microbiology. All rights reserved. No part of this publication may be reproduced or transmitted in whole or in part or reutilized in any form or by any means, electronic or mechanical, including photocopying and recording, or by any information storage and retrieval system, without permission in writing from the publisher.
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Library of Congress Cataloging-in-Publication Data
Names: Wooley, Dawn P., editor. | Byers, Karen B., editor.
Title: Biological safety : principles and practices / edited by Dawn P. Wooley, Department of Neuroscience, Cell Biology and Physiology, Wright State University, Dayton, OH, Karen B. Byers, Dana Farber Cancer Institute, Boston, MA.
Description: 5th edition. | Washington, DC : ASM Press, [2017] | Includes index.
Identifiers: LCCN 2017000395 (print) | LCCN 2017004110 (ebook) | ISBN 9781555816209 (print) | ISBN 9781683673132 (ebook)
Subjects: LCSH: Microbiological laboratories—Safety measures. | Biological laboratories—Safety measures.
Classification: LCC QR64.7 .L33 2017 (print) | LCC QR64.7 (ebook) | DDC 570.289—dc23
LC record available at https://lccn.loc.gov/2017000395
doi:10.1128/9781555819637
Printed in the United States of America
10 9 8 7 6 5 4 3 2 1
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Contents
INTRODUCTION
Contributors
Foreword—Caryl P. Griffin and James Welch
Preface
SECTION I. HAZARD IDENTIFICATION
1. The Microbiota of Humans and Microbial Virulence Factors
Paul A. Granato
2. Indigenous Zoonotic Agents of Research Animals
Lon V. Kendall
3. Biological Safety Considerations for Plant Pathogens and Plant-Associated Microorganisms of Significance to Human Health
Anne K. Vidaver, Sue A. Tolin, and Patricia Lambrecht
4. Laboratory-Associated Infections
Karen Brandt Byers and A. Lynn Harding
SECTION II. HAZARD ASSESSMENT
5. Risk Assessment of Biological Hazards
Dawn P. Wooley and Diane O. Fleming
6. Protozoa and Helminths
Barbara L. Herwaldt
7. Mycotic Agents
Wiley A. Schell
8. Bacterial Pathogens
Travis R. McCarthy, Ami A. Patel, Paul E. Anderson, and Deborah M. Anderson
9. Viral Agents of Human Disease: Biosafety Concerns
Michelle Rozo, James Lawler, and Jason Paragas
10. Emerging Considerations in Virus-Based Gene Transfer Systems
J. Patrick Condreay, Thomas A. Kost, and Claudia A. Mickelson
11. Biological Toxins: Safety and Science
Joseph P. Kozlovac and Robert J. Hawley
12. Molecular Agents
Dawn P. Wooley
13. Biosafety for Microorganisms Transmitted by the Airborne Route
Michael A. Pentella
14. Cell Lines: Applications and Biosafety
Glyn N. Stacey and J. Ross Hawkins
15. Allergens of Animal and Biological Systems
Wanda Phipatanakul and Robert A. Wood
SECTION III. HAZARD CONTROL
16. Design of Biomedical Laboratory and Specialized Biocontainment Facilities
Jonathan T. Crane and Jonathan Y. Richmond
17. Primary Barriers and Equipment-Associated Hazards
Elizabeth Gilman Duane and Richard C. Fink
18. Primary Barriers: Biological Safety Cabinets, Fume Hoods, and Glove Boxes
David C. Eagleson, Kara F. Held, Lance Gaudette, Charles W. Quint, Jr., and David G. Stuart
19. Arthropod Vector Biocontainment
Dana L. Vanlandingham, Stephen Higgs, and Yan-Jang S. Huang
20. Aerosols in the Microbiology Laboratory
Clare Shieber, Simon Parks, and Allan Bennett
21. Personal Respiratory Protection
Nicole Vars McCullough
22. Standard Precautions for Handling Human Fluids, Tissues, and Cells
Debra L. Hunt
23. Decontamination in the Microbiology Laboratory
Matthew J. Arduino
24. Packing and Shipping Biological Materials
Ryan F. Relich and James W. Snyder
SECTION IV. ADMINISTRATIVE CONTROL
25. Developing a Biorisk Management Program To Support Biorisk Management Culture
LouAnn C. Burnett
26. Occupational Medicine in a Biomedical Research Setting
James M. Schmitt
27. Measuring Biosafety Program Effectiveness
Janet S. Peterson and Melissa A. Morland
28. A "One-Safe" Approach: Continuous Safety Training Initiatives
Sean G. Kaufman
29. Biosafety and Biosecurity: Regulatory Impact
Robert J. Hawley and Theresa D. Bell Toms
SECTION V. SPECIAL ENVIRONMENTS
30. Biological Safety and Security in Teaching Laboratories
Christopher J. Woolverton and Abbey K. Woolverton
31. Biosafety in the Pharmaceutical Industry
Brian R. Petuch
32. Biosafety Considerations for Large-Scale Processes
Mary L. Cipriano, Marian Downing, and Brian R. Petuch
33. Veterinary Diagnostic Laboratories and Necropsy
Timothy Baszler and Tanya Graham
34. Special Considerations for Animal Agriculture Pathogen Biosafety
Robert A. Heckert, Joseph P. Kozlovac, and John T. Balog
35. Biosafety of Plant Research in Greenhouses and Other Specialized Containment Facilities
Dann Adair, Sue Tolin, Anne K. Vidaver, and Ruth Irwin
36. Biosafety Guidelines for Working with Small Mammals in a Field Environment
Darin S. Carroll, Danielle Tack, and Charles H. Calisher
37. Components of a Biosafety Program for a Clinical Laboratory
Michael A. Pentella
38. Safety Considerations in the Biosafety Level 4 Maximum-Containment Laboratory
David S. Bressler and Robert J. Hawley
Index
Contributors
Dann Adair
Conviron, Pembina, North Dakota
Deborah M. Anderson
Laboratory for Infectious Disease Research and Department of Veterinary Pathobiology, University of Missouri, Columbia, Missouri
Paul E. Anderson
Laboratory for Infectious Disease Research and Department of Veterinary Pathobiology, University of Missouri, Columbia, Missouri
Matthew J. Arduino
Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia
John T. Balog
U.S. Food and Drug Administration, Office of Operations, Employee Safety and Environmental Management, Silver Spring, Maryland
Timothy Baszler
Washington State University, Paul G. Allen School for Global Animal Health, Pullman, Washington
Allan Bennett
Public Health England, Biosafety, Porton, Salisbury, Wiltshire, United Kingdom
David S. Bressler
Centers for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia
LouAnn C. Burnett
International Biological and Chemical Threat Reduction, Sandia National Laboratories, Albuquerque, New Mexico
Karen Brandt Byers
Dana Farber Cancer Institute, Boston, Massachusetts
Charles H. Calisher
Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado
Darin S. Carroll
Poxvirus and Rabies Branch, Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia
Mary L. Cipriano
Abbott Laboratories, North Chicago, Illinois (retired)
J. Patrick Condreay
pc Biosafety Consulting Services, LLC, Carrboro, North Carolina
Jonathan T. Crane
HDR, Inc., Atlanta, Georgia
Marian Downing
Abbott Laboratories, North Chicago, Illinois (retired)
Elizabeth Gilman Duane
Environmental Health and Engineering Inc., Needham, Massachusetts
David C. Eagleson
The Baker Company, Inc., Sanford, Maine
Richard C. Fink
Environmental Health and Engineering Inc., Needham, Massachusetts, and Pfizer (retired)
Diane O. Fleming
Biological Safety Professional (retired), Mitchellville, Maryland
Lance Gaudette
The Baker Company, Inc., Sanford, Maine
Tanya Graham
Biosafety Consulting for Veterinary Medicine, LLC, Esteline, South Dakota
Paul A. Granato
Department of Pathology, SUNY Upstate Medical University, Syracuse, New York, and Laboratory Alliance of Central New York, LLC, Liverpool, New York
A. Lynn Harding
Biosafety Consultant, Chattanooga, Tennessee
J. Ross Hawkins
Division of Advanced Therapies, National Institute for Biological Standards and Control a centre of the Medicines and Healthcare Regulatory Agency, South Mimms, Herts, United Kingdom
Robert J. Hawley
Consultant, Biological Safety and Security, Frederick, Maryland
Robert A. Heckert
Robert Heckert Consulting, Palm Desert, California
Kara F. Held
The Baker Company, Inc., Sanford, Maine
Barbara L. Herwaldt
Centers for Disease Control and Prevention, Parasitic Diseases Branch, Atlanta, Georgia
Stephen Higgs
Biosecurity Research Institute, Kansas State University, Manhattan, Kansas
Yan-Jang S. Huang
Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas
Debra L. Hunt
Duke University, Durham, North Carolina
Ruth Irwin
Information Systems for Biotechnology, Virginia Polytechnic Institute & State University, Blacksburg, Virginia
Sean G. Kaufman
Behavioral-Based Improvement Solutions, Woodstock, Georgia
Lon V. Kendall
Department of Microbiology, Immunology and Pathology and Laboratory Animal Resources, Colorado State University, Fort Collins, Colorado
Thomas A. Kost
GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina (retired)
Joseph P. Kozlovac
USDA ARS Office of National Programs, Animal Production & Protection, Beltsville, Maryland
Patricia Lambrecht
Department of Plant Pathology, University of Nebraska-Lincoln, Lincoln, Nebraska
James Lawler
Navy Medical Research Center, Clinical Research, Fort Detrick, Maryland
Travis R. McCarthy
Laboratory for Infectious Disease Research, University of Missouri, Columbia, Missouri
Nicole Vars McCullough
3M, Personal Safety Division, Saint Paul, Minnesota
Claudia A. Mickelson
EHS Office, Massachusetts Institute of Technology, Cambridge, Massachusetts (retired)
Melissa A. Morland
University of Maryland, Baltimore, Baltimore, Maryland
Jason Paragas
Lawrence Livermore National Laboratory, Global Security, Livermore, California
Simon Parks
Biosafety, Air and Water Microbiology Group, Public Health England, Porton Down, Wiltshire, United Kingdom
Ami A. Patel
Laboratory for Infectious Disease Research, University of Missouri, Columbia, Missouri
Michael A. Pentella
Massachusetts Department of Public Health, State Public Health Laboratory, Jamaica Plain, Massachusetts
Janet S. Peterson
Biosafety Consultant, Ellicott City, Maryland
Brian R. Petuch
Global Safety & Environment, Merck, West Point, Pennsylvania
Wanda Phipatanakul
Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts
Charles W. Quint, Jr.
The Baker Company, Inc., PO Sanford, Maine
Ryan F. Relich
Division of Clinical Microbiology, Indiana University Health Pathology Laboratory, and
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana
Jonathan Y. Richmond
Bsafe.us, Southport, North Carolina
Michelle Rozo
Navy Medical Research Center, Clinical Research, Fort Detrick, Maryland
Wiley A. Schell
Department of Medicine, Division of Infectious Diseases and International Health, Duke University, Durham, North Carolina
James M. Schmitt
Occupational Medical Service, National Institutes of Health, Bethesda, Maryland
Clare Shieber
Public Health England, Biosafety, Air and Water Microbiology Group, Porton, Salisbury, Wiltshire, United Kingdom
James W. Snyder
Department of Pathology and Laboratory Medicine, University of Louisville, Louisville, Kentucky
Glyn N. Stacey
Division of Advanced Therapies, National Institute for Biological Standards and Control a centre of the Medicines and Healthcare Regulatory Agency, Blanche Lane, South Mimms, Herts, United Kingdom
David G. Stuart
The John M. Eagleson, Jr. Institute, Kennebunk, Maine
Danielle Tack
Poxvirus and Rabies Branch, Centers for Disease Control and Prevention, Atlanta, Georgia
Sue A. Tolin
Department of Plant Pathology, Physiology and Weed Science, Virginia Polytechnic Institute & State University, Blacksburg, Virginia
Theresa D. Bell Toms
Leidos Biomedical Research Inc., National Cancer Institute at Frederick, Frederick, Maryland
Dana L. Vanlandingham
Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas
Anne K. Vidaver
Department of Plant Pathology, University of Nebraska-Lincoln, Lincoln, Nebraska
Robert A. Wood
Department of Pediatrics, Division of Allergy and Immunology, Johns Hopkins University, Baltimore, Maryland
Dawn P. Wooley
Department of Neuroscience, Cell Biology and Physiology, Wright State University, Dayton, Ohio
Abbey K. Woolverton
Department of Epidemiology and Biostatistics, Milken Institute School of Public Health, George Washington University, Washington, DC
Christopher J. Woolverton
Department of Biostatistics, Environmental Health Science and Epidemiology, College of Public Health, Kent State University, Kent, Ohio
Foreword
On October 29, 1997, a non-human primate research worker was transferring macaques from a transport cage to a squeeze cage preceding a routine annual physical. One of the macaques became agitated, and as he jumped, his tail flicked material from the bottom of the cage into the face and eye of the researcher. On December 10, 1997, that vivacious and talented 22-year-old worker, Elizabeth “Beth” Griffin, died as a result of that innocuous event.
Beth’s death was initiated by an ocular exposure to the Herpes simian B virus (Macacine herpesvirus 1). Her case was the first known exposure to be the result of something other than a bite or a scratch. An Agnes Scott College graduate, Beth—a dancer—died from an encephalitic disease that first paralyzed her from the neck down before finally causing her death.
Beth’s death gained national attention in the U.S. media. It was a featured story on a network newsmagazine. The incident gained international attention in the world of research. The world—especially the research world—wanted to know how such a thing could ever happen and what could be done to ensure it never happened again.
A number of things could have been done that would have meant this story would never be read. There were systematic failures in the occupational health response to her exposure. There were failures in the health care system. There were things Beth could have done, such as wear goggles while handling the monkeys or use the nearby eyewash stations within 5 minutes of her exposure. An emergency response measure could have provided a simple postexposure prophylactic prescription taken shortly after her incident. These actions and others as elements of an institutional culture of safety—Prevention, Detection, and Response—could have changed everything.
Two years after her death, Beth’s family established a nonprofit foundation to increase safety and occupational health awareness for people who worked with non-human primates. With the collaborative assistance of organizations such as the Association of Primate Veterinarians (APV), the American Association for Laboratory Animal Science (AALAS), and the American College of Laboratory Animal Medicine (ACLAM), many changes were made in processes and responses to exposures. Many people working in non-human primate research environments began carrying cards, quickly tagged as “Beth Cards,” that informed medical personnel to take specific measures to rule out B virus exposure first—not last—if the person was exhibiting certain viral symptoms.
In 2003, the world became gripped in an outbreak of a disease called SARS (severe acute respiratory syndrome). The outbreak began in China, but because of mobility the disease soon began popping up elsewhere. As Beth’s death had been a tipping point for safety awareness in working with non-human primates, the SARS outbreak and the global response of expanding laboratory capacity to detect and identify emerging infectious diseases became a massive springboard for biosafety.
The "Amerithrax" incident of 2001 had already sparked international attention to practices used in working with certain biological agents. The concepts of biosafety and biosecurity preceded all of these incidents by decades, but never had there been such total community attention to the potential risks of biological exposures.
At the encouragement of those groups with whom we had already collaborated, the Elizabeth Griffin Research Foundation reached out with our “no more Beth Griffin tragedies” message to the American Biological Safety Association to assist in highlighting awareness of and response to the exposure risks that those who work with biological agents face on a rather routine basis. With their assistance—and that of a growing number of similar professional organizations around the world—biosafety is a front-burner issue in conducting safe and responsible science. Much has been done to increase the awareness, research, and application of sound protocols that both reduce the risk of exposure and improve the quality of response to an exposure should one occur. The very truth that you are reading this book on biosafety and biosecurity is proof enough of how far this has come.
Good science is safe science. If the science isn’t safe, it isn’t good. Nothing can be more damaging to the reputation of a research institution or to the public view of the value of science than a bungled exposure issue or the appearance of cutting corners on safety in order to accomplish something. Biological risks are very different from many others in that they are most often not immediately evident, due to incubation periods. There are no immediate detection capabilities as with chemical or radiation risks, since biological manifestation may easily be delayed and often misdiagnosed. Compound those issues with the fact that many biological agents have highly contagious, often lethal capabilities, and we quickly see it’s not just the laboratory worker at risk.
Watchfulness, attention, caution, and prudence are all required whenever someone does anything that places individuals beyond themselves at risk. To engage in biological research requires that you exercise caution and follow protocols, not only for your safety but also for the safety of the community and world that surrounds you. It is not an option or a luxury. It is a necessity. Every risk, no matter how small it may seem, must be considered, assessed, and properly mitigated. The techniques of safety and security are every bit as important as the techniques used in your research.
Before getting into the technical nuts and bolts of biosafety and biosecurity, please keep these basics in mind.
We adhere to the words spoken by Thomas Huxley at the opening of The Johns Hopkins University in Baltimore, Maryland. In his remarks, Huxley noted that “the end of life is not knowledge, but action.” On behalf of the Elizabeth R. Griffin Research Foundation and our collaborative partners worldwide, we encourage that you not just learn the material in this book but act upon, promote, and add to this body of knowledge throughout your scientific career.
Caryl P. Griffin, MDiv, President and Founder
James Welch, Executive Director
Elizabeth R. Griffin Foundation
www.ergriffinresearch.org
Preface
It is with a great sense of honor and reverence that we take over the reins of editing this book from our esteemed colleagues, Diane O. Fleming and Debra L. Hunt. It is our hope that this 5th edition of Biological Safety: Principles and Practices remains the main text in the field of biosafety. We are indebted to the many authors who have contributed to this edition. This book serves as a valuable resource not only for biosafety professionals, but also for students, staff, faculty, and clinicians who are working with or around potentially biohazardous materials in research laboratories, medical settings, and industrial environments. Those who supervise biosafety or laboratory staff members will also benefit from this book.
We decided to keep the overall structure similar to the previous edition, with five major sections. Eight new chapters were added on the following topics: molecular agents, arthropod vector biocontainment, aerobiology, training programs, veterinary and greenhouse biosafety, field studies, and clinical laboratories. Biosafety Practices is not a separate chapter in this edition; the concepts have been incorporated into relevant chapters. Similarly, the information on prions was incorporated into the new chapter on molecular agents. The title of the last section was changed from “Special Considerations” to “Special Environments” and some chapters were moved out of this section to keep the focus on unique settings encountered in biosafety practice. Since regulatory guidelines are always changing, we have directed our readers to online sources for the most up-to-date information. Chapters have been made to be more fluid and stand-alone by minimizing references to other chapters. We are fortunate to have color in this new edition.
Both of this edition’s editors are Certified Biosafety Professionals, but we came to the field of biosafety through different avenues, giving us complementary perspectives on the topic. Dawn Wooley became intensely interested in biosafety during her graduate days at Harvard while researching the newly discovered AIDS viruses. These were the days before there were important administrative controls such as the Bloodborne Pathogen Standard. In trying to protect herself and others around her from these newly emerging pathogens, Dawn developed a love for the field of biosafety that has persisted until today. Karen Byers developed a keen interest in biosafety while working with measles in Harvard research laboratories. An appointment to the Institutional Biosafety Committee inspired her to become a biosafety professional. She is very grateful for Lynn Harding’s mentorship and the opportunities for professional development and leadership provided by colleagues in the American Biological Safety International (ABSA).
Professional organizations such as ABSA, the American Society of Microbiology (ASM), the American Public Health Association (APHL), the Clinical and Laboratory Standards Institute (CLSI), and the American Association for Laboratory Animal Science (AALAS) have played a key role in fostering the development and implementation of evidence-based biosafety practice. The Foreword to this edition reminds us of the importance of this endeavor.
Gregory W. Payne, Senior Editor, ASM Press, was instrumental in pushing for the update of this book, and he provided much-needed guidance and inspiration. We thank Ellie Tupper and Lauren Luethy for their expert assistance with the production of this book.
We hope that our readers enjoy the book as much as we have appreciated the opportunity to work on it for you and the rest of the biosafety community. Be safe!
Dawn P. Wooley
Karen B. Byers
SECTION I |
Hazard Identification |
1. The Microbiota of Humans and Microbial Virulence Factors Paul A. Granato 2. Indigenous Zoonotic Agents of Research Animals Lon V. Kendall 3. Biological Safety Considerations for Plant Pathogens and Plant-Associated Microorganisms of Significance to Human Health Anne K. Vidaver, Sue A. Tolin, and Patricia Lambrecht 4. Laboratory-Associated Infections Karen Brandt Byers and A. Lynn Harding |
The Microbiota of Humans and Microbial Virulence Factors |
1 |
PAUL A. GRANATO |
“The 1990s have been marked by a renewed recognition that our human species is still locked in a Darwinian struggle with our microbial and viral predators.” Although this unreferenced quotation was made by Nobel Laureate Joshua Lederberg, as he was discussing the acquired immunodeficiency syndrome (AIDS) and multidrug-resistant Mycobacterium tuberculosis epidemics that emerged in the early 1990s, his comment could also apply to almost any infectious disease process that has occurred since the recognition of the germ theory of disease in the late 1880s. For as we journey through the 21st century, and despite the advances of modern medicine and the continual development of new vaccines and anti-infective therapeutic agents, the human species continues to battle microbial predators in this Darwinian struggle for survival.
The human normal flora consists of an ecological community of commensal, symbiotic, and pathogenic microorganisms in dynamic balance that literally share and inhabit our body spaces throughout life. In 2001, Lederberg (1) coined the term “microbiota” to describe these microbial communities that were characterized by using cultural methods. Subsequently, in 2008, the Human Microbiome Project (HMP) was funded by the National Institutes of Health to use noncultural methods to study how changes in the human microbiome are associated with health and disease (2). The HMP used genetic-based, molecular methods, such as metagenomics and genome sequencing, to characterize all microbes present in a body site, even those that could not be cultured. As such, by using metagenomics (which provides a broad genetic perspective on a single microbial community) and extensive whole-genome sequencing (which provides a genetic perspective on individual microorganisms in a given microbial community), the HMP provided a more comprehensive understanding of the microorganisms that inhabit a particular body site through genetic analysis.
The HMP studies (3) have shown that even healthy individuals differ remarkably in the microbes that occupy body sites such as the skin, mouth, intestine, and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics, and early microbial exposure have all been implicated. These studies have also led some investigators to conclude that the human microbiome may play a role in autoimmune diseases like diabetes, rheumatoid arthritis, muscular dystrophy, multiple sclerosis, fibromyalgia, and perhaps some cancers (4). Others have proposed that a particular mix of microbes in the intestine may contribute to common obesity (5–7). It has also been shown that some of the microbes in the human body can modify the production of neurotransmitters in the brain that may possibly modify schizophrenia, depression, bipolar disorder, and other neurochemical imbalances (8).
The dynamics of this host–parasite relationship for survival are in a continual state of change. In health, a balance exists between the host and the microbe that allows for the mutual survival and coexistence of both. This balance is best maintained when humans have operative host defense mechanisms and are not exposed to any particular infectious microbial agent. The three major host defense mechanisms that must be operative to maintain this balance and the health of the human host are (i) intact skin and mucous membranes, (ii) a functional group of phagocytic cells consisting principally of the reticuloendothelial system (RES), and (iii) the ability to produce a humoral immune response. Defects in any one or combination or all of these host defense mechanisms will shift the balance in favor of the microbe and predispose the host to the risk of developing an infectious disease process. For example, breaks in skin or mucous membranes due to accidents, trauma, surgery, or thermal injury may serve as a portal of entry for microorganisms to produce infection. In addition, the inability to phagocytize microorganisms effectively by the RES due to lymphoma or leukemia and the inability to produce functional humoral antibodies due to defects in plasma cells or exposure to immunosuppressive agents (i.e., drugs, irradiation, etc.) may also predispose to the development of infection. This balance in favor of the microbe may be shifted back toward the host through the use of antimicrobial agents and/or the administration of vaccines for the treatment and prevention of disease. Unfortunately, as these agents or selective pressures may adversely affect the survival of the microbe, these developments are often followed by a shift in balance back in favor of the ever-adaptable microbe by, perhaps, acquiring new mechanisms for producing human disease or resisting the action of an antimicrobial agent.
The microbial world consists of bacteria, fungi, viruses, and protozoa that represent over several hundred thousand known species. The great majority of these, however, are not involved in any dynamic relationship with the human host because they are incapable of surviving or causing disease in humans. By comparison, those microorganisms that are involved in the dynamic relationship with the host are limited in number, consisting of fewer than 1,000 known microbial species. It is this limited group of microorganisms that is the focus of discussion in this chapter.
The relationships that exist between the human host and the microbial world are varied and complex. When a microorganism that is capable of causing disease becomes established in the body, this process is called an infection, and an infection that produces symptoms in a human is called an infectious disease. By contrast, persistence of microorganisms in a particular body site (such as the normal microbial flora, as is discussed in a subsequent section of this chapter) is often referred to as colonization rather than infection. Importantly, infection or colonization does not necessarily lead to the development of an infectious disease. If host defenses are adequate, a person may be infected by a disease-causing microorganism for an indefinite period without any signs or symptoms of disease. Such individuals are referred to as asymptomatic carriers or simply carriers who have asymptomatic or subclinical infection. These asymptomatic carriers serve as important reservoirs for transmission of the infecting organisms to susceptible hosts who may subsequently develop symptomatic disease.
The ability of certain microorganisms to infect or cause disease depends on the susceptibility of the host, and there are notable species differences in host susceptibility for many infections. For instance, dogs do not get measles and humans do not get distemper. Thus, the term pathogenicity, which is defined as the ability of a microorganism to cause disease, must be qualified according to the host species involved. Microorganisms that do not normally produce disease in the healthy human host are often called saprophytes, commensals, or nonpathogens.
In recent years, increasing numbers of infectious diseases have been caused by microorganisms that were previously considered nonpathogenic. These infectious diseases often develop in patients whose surface/barrier, cellular, or immunologic defenses are compromised by such things as trauma, genetic defects, underlying disease, or immunosuppressive therapy. Microorganisms that are frequent causes of disease only in the immunocompromised host or when skin or mucosal surfaces or barriers are breached are called opportunistic pathogens. Opportunistic pathogens are often saprophytes that rarely cause disease in individuals with functional host defense mechanisms.
Pathogenicity refers to the ability of a microorganism to cause disease, and virulence provides a quantitative measure of this property. Virulence factors refer to the properties that enable a microorganism to establish itself on or within a host and enhance the organism’s ability to produce disease. Virulence is not generally attributable to a single discrete factor but depends on several parameters related to the organism, the host, and their interaction. Virulence encompasses two general features of a pathogenic microorganism: (i) invasiveness, or the ability to attach, multiply, and spread in tissues, and (ii) toxigenicity, the ability to produce substances that are injurious to human cells. Highly virulent, moderately virulent, and avirulent strains may occur within a single species of organisms.
The microorganisms that cause human infectious diseases are acquired from two major sources or reservoirs: those acquired from outside the body, called exogenous reservoirs, and those infectious diseases that result from microorganisms that inhabit certain body sites, called endogenous reservoirs. Most exogenous infections are acquired from other individuals by direct contact, by aerosol transmission of infectious respiratory secretions, by ingestion of contaminated food or drink, or indirectly through contact with contaminated inanimate objects (often called fomites). Some exogenous infections may also be acquired by puncture of the skin during an insect or animal bite and, perhaps, by occupational exposure from sharps. Endogenous infections occur more commonly than exogenous infections and are acquired from microorganisms that reside normally on various body sites (called normal commensal flora) gaining access to anatomic sites that are normally sterile in health.