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AIDS SCIENCE AND SOCIETY

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AIDS SCIENCE AND SOCIETY

SEVENTH EDITION

HUNG Y. FAN ROSS F. CONNER

LUIS P. VILLARREAL University of California, Irvine

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Library of Congress Cataloging-in-Publication Data Fan, Hung, 1947-

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AIDS : science & society / Hung Y. Fan, Ross F. Conner, and Luis P. Villarreal — 7th ed. p. ; cm.

ISBN 978-1-4496-8332-0 I. Conner, Ross F. II. Title. [DNLM: 1. Acquired Immunodeficiency Syndrome. 2. HIV Infections. WC 503] 614.5'99392—dc23

2012039131

6048

Printed in the United States of America 17 16 15 14 13 10 9 8 7 6 5 4 3 2 1

To our HIV-infected friends and acquaintances who are courageously battling the disease or who have succumbed to it.

In their honor, and to hasten the day when this book is no longer necessary, a portion of the royalties from this book will be donated

to foundations and community organizations dedicated to AIDS research and service.

Brief Contents

CHAPTER 1 Introduction: An Overview of AIDS

CHAPTER 2 Concepts of Infectious Disease and a History of Epidemics

CHAPTER 3 The Immune System

CHAPTER 4 Virology and HIV

CHAPTER 5 Clinical Manifestations and Treatment of AIDS

CHAPTER 6 Epidemiology and AIDS

CHAPTER 7 Modes of HIV Transmission and Personal Risk Factors

CHAPTER 8 Individual Assessments of HIV Risk

CHAPTER 9 Prevention of AIDS

CHAPTER 10 Living with AIDS: Human Dimensions

CHAPTER 11 Living with AIDS: Societal Dimensions

CHAPTER 12 Future Directions in Combating AIDS

Glossary Appendix: Reference Resources Index

Contents

Preface

CHAPTER 1 Introduction: An Overview of AIDS AIDS in Brief The AIDS Epidemic

CHAPTER 2 Concepts of Infectious Disease and a History of Epidemics Factors That Affect the Spread of Epidemics

Host and Virus Populations The Transmission Rate Population Densities and Infections Chronic Infections Controlling Infectious Diseases

A History of Epidemics The Old World The New World

Modern Concepts of Infectious Disease and Koch’s Postulates Epidemics in Modern Times

Syphilis: The Social Problems with a Sexually Transmitted Disease Infections from Other Species

CHAPTER 3 The Immune System Blood

Cells of the Blood Red Blood Cells White Blood Cells

The Lymphatic Circulation Innate Immunity Adaptive Immunity

B-Cells and Humoral Immunity: The Generation of Antibodies Antibodies How Do B-Lymphocytes Respond to New Antigens? The Primary Immune Response How Do Antibodies Fight Infections? Immunological Memory The Secondary Immune Response Vaccines Tolerance

T-Cells and Cell-Mediated Immunity Tkiller Lymphocytes Thelper Lymphocytes T-Lymphocyte Recognition of Antigen-Containing Cells T-Cell Memory

CHAPTER 4 Virology and HIV A General Introduction to Viruses

What Are Viruses? How Does a Virus Infect a Host? A Typical Virus Infection Cycle How Do We Treat Viral Infections?

The Life Cycle of a Retrovirus The AIDS Virus: HIV

Features of HIV The Nature of the HIV Receptor Additional Genes Killing of Thelper Lymphocytes Nonlytic Infection of Macrophages Dendritic Cells and HIV Co-Receptors for HIV

The Effects of HIV Infection in Individuals The HIV Antibody Test

Potential Problems with the HIV Antibody Test How Does HIV Evade the Immune System? Azidothymidine (AZT): The First Effective Drug Treatment in HIV/AIDS

Limitations of AZT Protease Inhibitors: Another Class of Drugs Against HIV

Where Did HIV Come From?

CHAPTER 5 Clinical Manifestations and Treatment of AIDS Exposure, Infection, and Disease

Exposure Versus Infection Infection Versus Disease

HIV Infection in Untreated Individuals Primary Infection and the Asymptomatic Period Mononucleosis-Like Illness Brain Infection (Encephalopathy) The Asymptomatic Period Initial Disease Symptoms Damage to the Immune System and Full-Blown AIDS AIDS

High Turnover of Thelper Cells in AIDS Patients Mutation and Evolution of HIV During Infection Antiviral Drugs for HIV

Reverse Transcriptase Inhibitors Protease Inhibitors Integrase Inhibitors Fusion Inhibitors CCR5 Antagonists

Clinical Management of HIV-Infected Individuals Monitoring Infection and Disease Antiretroviral Therapy (ART) Limitations and Uncertainties in ART Therapies Timing the Initiation of ART Prophylaxis for Opportunistic Infections

ART in Prevention of HIV Infections

CHAPTER 6 Epidemiology and AIDS An Overview of Epidemiology and AIDS Basic Concepts in Epidemiology

Descriptive Studies Analytical Studies Correlations Criteria for a Causal Relationship

Epidemiology and AIDS in the United States The Current Picture of AIDS in the United States Epidemiology and Modes of HIV Transmission The Effectiveness of AZT The Changing Face of AIDS

AIDS Around the World AIDS in Africa AIDS in Asia New Areas of Rapid Spread

HIV Subgroups and Clades

CHAPTER 7 Modes of HIV Transmission and Personal Risk Factors Biological Bases of HIV Transmission

Sources of Infectious HIV Stability of HIV Targets for HIV Infection

Modes of HIV Transmission Activities Not Associated with HIV Transmission: Casual Contact Activities Associated with HIV Transmission: Birth, Blood, and Sex

CHAPTER 8 Individual Assessments of HIV Risk Introduction to Individual Decision Making and Action Risk Assessment

Normative Model Subjective Probability Model

HIV Testing and Risk Assessment Nature and Accuracy of the HIV Test Testing Options

CHAPTER 9 Prevention of AIDS Disease Prevention and Health Promotion Models of Health Behavior Change

Health Belief Model Health Decision Model Precaution-Adoption Process Model

Principles of Health Behavior Change The Cognitive Principle

The Emotional Principle The Behavioral Principle The Interpersonal Principle The Social Ecological Principle The Structural Principle The Scientific Principle

Examples of HIV/AIDS Prevention Programs AIDS Prevention Among Young Gay and Bisexual Men AIDS Prevention Among Mexican Migrant Farm Workers

CHAPTER 10 Living with AIDS: Human Dimensions Theoretical Perspectives from Social Psychology

Role Theories Cognitive Theories

Human Dimensions of HIV/AIDS Confronting the News of Infection Accepting the Reality of Infection Opportunities and Challenges of Drug Therapies

CHAPTER 11 Living with AIDS: Societal Dimensions Theoretical Concepts

Prejudice Discrimination

Societal Dimensions of HIV/AIDS Needle Exchange for Injection Drug Users HIV Prevention for Teens Healthcare Practices

CHAPTER 12 Future Directions in Combating AIDS Future Directions for Biomedical Efforts

Prevention of Infection Treatment of Infected Individuals

Future Directions for Social Efforts Education Research

A Final Note of Optimism: Time Is on Our Side

Glossary Appendix: Reference Resources Index

Preface

THE PURPOSE OF THIS TEXT is to provide the nonspecialized student with a firm overview of AIDS from biomedical and psychosocial perspectives. The biological aspects include cellular and molecular descriptions of the immune system and the AIDS virus (human immunodeficiency virus, or HIV). The consequences of HIV infection from cell to organism are also covered with a clinical description of the disease. We then move from the organism level to the interorganism level covering both the psychological and social aspects of HIV/AIDS. These topics can be covered only in a survey fashion because of the comprehensive nature of this approach and the additional aim of making this text appropriate for a one-quarter (or semester) course (or part of such a course). We focus on presenting the relevant fundamental principles. Following a brief presentation of these principles for each topic, we generalize and apply these concepts to the case of AIDS.

This book began as The Biology of AIDS. The first edition of AIDS: Science and Society expanded from The Biology of AIDS and included consideration of social issues related to HIV/AIDS: personal risk assessment, HIV prevention, and the human and societal dimensions of living with HIV/AIDS. In the current edition of AIDS: Science and Society, we have provided updates and new sections in several of the chapters and provided the latest statistics on AIDS that were available as the book went to press. Chapter 3, on immunology, has been modified to include the concepts of adaptive and innate immunity. The book contains a reference appendix in which students can obtain additional information on AIDS. A major feature of this appendix is the inclusion of several organizations that have websites students can explore to find up-to-date information about AIDS.

This book is patterned after a one-quarter course, AIDS Fundamentals, taught at the University of California, Irvine. Approximately half the course covers biomedical aspects of AIDS, and the other half covers social issues raised by the disease. The text represents the material covered in the course. At UCI, AIDS Fundamentals is open to all undergraduate students and is taught with the assumption that they have had a high school–level modern biology course. The material contained in Chapters 3 (immunology), 4 (virology), 6 (epidemiology), 9

(preventing HIV), and 10 (living with AIDS) is covered in three hours of lecture per chapter. Material covered in the other chapters is taught in a single one and one-half hour lecture per chapter. We have found that students are able to assimilate and retain the material when delivered at this rate. The course includes another important component: small discussion groups led by students who previously took the class. These peerled groups use experiential exercises as a catalyst for a deeper understanding of the human and social aspects of HIV/AIDS. More details about this aspect of the course are in the instructor’s resources available from Jones & Bartlett Learning. Another important feature of the AIDS Fundamentals course is two panel presentations by people affected by HIV/AIDS: a panel of people living with AIDS and a panel of HIV/AIDS healthcare workers.

Most researchers and scholars in AIDS-related fields were unprepared for the dramatic impact of the AIDS epidemic when it emerged in 1981. As virologists and social scientists, we might have expected modern biomedical technology to provide a quick technical solution or to at least prevent, through vaccine development, the spread of this major new viral epidemic. Although there has been biomedical progress, it is now clear that the HIV/AIDS issues pose new and unforeseen difficulties with no quick biological solution in sight. These difficulties challenge both our scientific abilities and the ability of our society to respond appropriately. It is our goal to provide students with a conceptual framework of the issues raised by HIV/AIDS so that they will be able to deal better with the challenges posed by this disease. This is particularly important because new information about scientific aspects of HIV/AIDS appears regularly; with this information comes new implications for the clinical, social, psychological, legal, and ethical aspects of the disease. We hope that the framework provided in this book will help students understand and make informed decisions about HIV/AIDS-related issues as they develop in the future.

Ancillaries For Students Jones & Bartlett Learning has developed a Navigate Companion Website especially for this text, revised and updated by Anne Bongiorno of SUNY Plattsburgh, featuring numerous interactive and informative learning resources that gauge understanding and help students study more effectively. Please visit go.jblearning.com/AIDSsociety7eCWS for useful study tools, including summaries of the main points from each chapter, short-answer review questions, and additional links to HIV/AIDS-related sites. Links to the organizations

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mentioned in the appendix can also be found here.

For Instructors The following materials are available for download:

• The PowerPoint® Image Bank provides all of the illustrations, photographs, and tables (to which Jones & Bartlett Learning holds the copyright or has permission to reprint digitally) inserted into PowerPoint slides. With the Microsoft® PowerPoint program, you can quickly and easily copy individual image slides into your existing lecture slides.

• A set of PowerPoint Lecture Outline Slides provides outline summaries and relevant images for each chapter of AIDS: Science and Society, Seventh Edition. Instructors with the Microsoft PowerPoint software can customize the outlines, figures, and order of presentation.

For more information about these resources, please visit go.jblearning.com/AIDSsociety7e.

Acknowledgments We thank David Fan, Elaine Vaughan, Michael Gorman, David Prescott, Cedric Davern, David Baltimore, and Frank Lilly for reading parts of the original manuscript and providing many helpful substantive and editorial comments. Kathryn Radke and Ian Trowbridge provided helpful suggestions for a previous revision; Ian also provided some of the content for the website linked to this book. Special thanks to the following reviewers who provided comments for this and previous revisions:

Amy Rex Smith, University of Massachusetts, Boston Anne Watson Bongiorno, SUNY Plattsburg Gopal Sankaran, West Chester University of Pennsylvania Ian Trowbridge, Salk Institute James D. Haynes, State University College at Buffalo James Rothenberger, University of Minnesota Robert Fullilove, Columbia University Karl A. Haushalter, Harvey Mudd College Kathryn Radke, University of California, Davis Michael R. Leonardo, Coe College

http://go.jblearning.com/AIDSsociety7e
Michael A. Sulzinski, University of Scranton Thomas P. Gariepy, Stonehill College Thomas C. Van Cott, Henry M. Jackson Foundation

Erin O’Connor, Michelle Bradbury, Lou Bruno, and Andrea DeFronzo of Jones & Bartlett Learning are responsible for production of this edition, and we are grateful for their assistance and gentle prodding. We also thank Michael Feldman and Emmett Carlson for their love and support.

The Authors Dr. Hung Fan is Professor of Virology in the Department of Molecular Biology and Biochemistry at the University of California, Irvine and Director of the UCI Cancer Research Institute. His research interest is in how retroviruses cause disease and induce cancer and AIDS.

Dr. Ross Conner is Professor Emeritus, School of Social Ecology, at the University of California, Irvine where he founded and directed the Center for Community Health Research at UCI. Dr. Conner continues his research in the area of community health promotion and disease prevention including HIV, working in partnership with communities of many types and sizes in the United States and abroad. His work also includes the evaluation of the effectiveness of social programs and public policies. He is the past president of the International Organisation for Cooperation in Evaluation.

Dr. Luis Villarreal is Professor of Virology in the Department of Molecular Biology and Biochemistry at the University of California, Irvine. Dr. Villarreal’s research interest is in the strategy of how viruses replicate and how they cause disease.

CHAPTER 1

Introduction: An Overview of AIDS

AIDS in Brief

The AIDS Epidemic

A report appeared in 1981 that initially drew little attention from infectious disease experts. In that report, Dr. Michael Gottlieb, at the University of California at Los Angeles, described a rare form of pneumonia occurring in homosexual men. Other reports from about the same time indicated that other homosexual men were developing a rare form of cancer. This new set of symptoms, a syndrome in medical terms, was eventually called acquired immune deficiency syndrome because the symptoms were consistent with damage to the immune system in previously healthy individuals. Moreover, this disease was not congenital or inherited but appeared to have been acquired. (We now know it results from infection by a virus.) Since then, the acronym AIDS, which is used to describe this disease, has become a prominent and permanent fixture in our language. It evokes a range of responses, including fear, hate, and mistrust. Some of these responses (hate, mistrust) are related to the association of AIDS with subcultural groups within our society, such as male homosexuals, who already have experienced discrimination. Other responses (fear) are due to the grave nature of the AIDS disease and the threat it may pose to society. This fear is because the AIDS epidemic continues—unlike many other major infectious diseases, which have been controlled by a combination of clinical treatments and public health measures.

AIDS in Brief

We now know that AIDS is caused by the human immunodeficiency virus (HIV), but it was originally observed by its effects on the immune system. An important clue was that AIDS patients often developed a lung infection (or pneumonia) caused by a fungus called Pneumocystis. This infection is very rare in healthy individuals, but patients with cancers of the immune system (lymphomas) were known to be susceptible to this disease. Lymphomas are usually treated by chemotherapy, which is intended to destroy the cancer cells. However, chemotherapy also unavoidably destroys many healthy immune cells along with the cancerous lymphoma cells. Thus, this type of pneumonia predominantly occurs in patients with damaged immune systems. Examination of AIDS patients confirmed that their immune systems were damaged. It had been known for some time that various other viral infections could damage cells of the immune system, but the severe damage seen with AIDS was unprecedented. Although doctors suspected early on that AIDS resulted from infection by a virus, it was not until 1984 that the virus (HIV) was finally isolated by both French and American researchers.

In addition to pneumonia, AIDS is associated with numerous other infections. These secondary infections are caused by various bacteria, protozoa, fungi, and other viruses. Usually, it is the secondary infection(s) (known as an opportunistic infection) that causes death in AIDS patients. In addition to secondary infections, AIDS patients frequently develop cancers, including lymphomas and an otherwise rare cancer called Kaposi’s sarcoma. HIV infection also can result in damage to brain cells. This damage leads to loss of mental function, referred to as AIDS dementia. Most of these opportunistic infections and some other effects of HIV infection can be explained by damage to the immune system.

HIV causes disease insidiously. The early stages of infection may not be noticed by the infected individual. The infected person may feel healthy and appear to be completely normal during this time (the asymptomatic period), but such a person is able to transmit the infection. The HIV incubation period (the time between initial infection and appearance of disease) is of variable duration and can be quite long (on average, 10 years or more). In contrast, for most common viral infections, such as colds or influenza, an incubation period of a few days or weeks is followed by apparent disease. This adds greatly to the difficulty of studying and controlling AIDS, because many people infected with the virus have not yet developed the disease.

The AIDS Epidemic

Despite the many different clinical symptoms that result from AIDS, medical investigators know a great deal about how AIDS is spread in our population. For example, it is now clear that HIV transmission requires close contact and that infection occurs by one of three routes: blood, birth, or sex. Casual contact does not lead to disease transmission.

Between 1981 (the beginning of the AIDS epidemic) and 2010, a total of 1,163,575 AIDS cases in the United States were reported to the national Centers for Disease Control and Prevention in Atlanta, Georgia. Of these cases, about 619,380 (53%) have died. Sexually active homosexual males were originally the major afflicted group and currently represent about 48% of these reported cases. Another 24% of the cases are male or female injection drug users, and 7% are male homosexual drug users. Another 20% result from heterosexual transmission, birth, or blood transfusion during the period when the American blood supply was not monitored for HIV antibodies (1981–1985).

In the relatively brief period since the beginning of the AIDS epidemic, AIDS has already had a major impact on death and disease in the United States. Currently, there are between 40,000 and 60,000 new cases of HIV infection every year, and the number of people dying from AIDS per year is currently approximately 17,000. In comparison, approximately 40,000 women die each year from breast cancer, and about 35,000 men die each year from prostate cancer. On the other hand, the average age of death from breast or prostate cancer is considerably older than for death from AIDS. The AIDS epidemic has had a particularly high impact on African Americans and Hispanics, who show rates of HIV infection that are three to six times higher than that of the general population.

The AIDS epidemic is not restricted to the United States. It can be found on all continents and hence is considered a pandemic. It is estimated that 22 million people in sub-Saharan Africa are infected with HIV. In Africa, HIV transmission predominantly results from heterosexual contact. Given the relatively poor medical support available in much of Africa, the number of deaths from AIDS will increase significantly. There are high levels of HIV infection in certain countries of Asia, and it is spreading explosively in some parts of eastern Europe. Because there is no cure for AIDS, these numbers are alarming. They indicate the clear potential of HIV/AIDS to spread unchecked, despite recent advances in modern medicine, epidemiology, virology, and recombinant DNA technology. This threat reminds us of earlier times when major infectious diseases devastated human populations.

Worldwide, AIDS now ranks as the fourth leading cause of death after heart disease, stroke, and acute lower respiratory infections. In Africa, it is the leading cause of death. How can we control this epidemic? An overview of the

relationship between epidemics and human populations may shed some light on this concern.

http://biology.jbpub.com/fan/aids/7e/

Connect to this book’s website: http://biology.jbpub.com/fan/aids/7e/. The site features summaries of the main points from each chapter, links to important AIDS-related websites, and short-answer-style review questions for each chapter.

http://biology.jbpub.com/fan/aids/7e/
http://biology.jbpub.com/fan/aids/7e/
CHAPTER 2

Concepts of Infectious Disease and a History of Epidemics

Factors That Affect the Spread of Epidemics Host and Virus Populations The Transmission Rate Population Densities and Infections Chronic Infections Controlling Infectious Diseases

A History of Epidemics The Old World The New World

Modern Concepts of Infectious Disease and Koch’s Postulates

Epidemics in Modern Times Syphilis: The Social Problems with a Sexually Transmitted Disease

Infections from Other Species

One of the great recent achievements of modern civilization has been the control of infectious diseases. Many of us may not personally know anyone who died from a contagious disease. In historic terms, this is a new development, one that began in the mid-twentieth century. In previous centuries, death from infectious disease was common, and whole populations were often affected.

When a population becomes infected with a contagious disease, an epidemic results. Epidemic derives from Greek and means “in one place among the

people.” To understand how an infectious disease can spread or remain established in a population, we must consider the relationship between an infectious disease agent and its host population. The study of diseases in populations is an area of medicine known as epidemiology.

Contagious diseases are spread by microorganisms, such as certain bacteria and viruses, that cause disease when they infect a susceptible person. This manner of disease transmission is a modern concept, known when it was developed as the germ theory of infectious disease. Before this understanding, earlier societies often used moral or religious explanations for infectious disease, and social practices developed that reflected those beliefs.

Factors That Affect the Spread of Epidemics

In this section, we will discuss factors that influence the spread of infectious diseases. Although many different microorganisms cause diseases, we will focus on viruses because HIV is a virus. The general principles are the same for other infectious microorganisms.

Host and Virus Populations An epidemic consists of infection of a number of individuals in a population. It is important to look at more than a single person to understand how diseases spread. Two populations must be considered: the human host and the infecting agent—in the case of AIDS, a virus. These two populations have a balanced host–parasite relationship. A viral infection can deplete or limit the population of its host, but a highly lethal virus that spreads too rapidly might kill all available hosts and lead to the extinction of both its host and itself. The course of an epidemic, however, is not always straightforward. It can be influenced by a number of other factors about the population:

1. The total number of hosts 2. Their birth rate 3. The rate at which susceptible individuals migrate into the population 4. The number of susceptible hosts who are not infected 5. The rate at which the disease can be transmitted from an infected

individual to an uninfected one 6. The number of infected individuals who die 7. The number who survive the infection and become immune or resistant to

further infection

Figure 2-1 shows a schematic relationship of people in a population with regard to a simple viral infection; all infected individuals either recover from the infection and become immune to it, or they die from it. The population can be divided into those who have not been infected by the virus (susceptibles), those who are infected, and those who have recovered from the infection and are immune to it.

Figure 2-1 Population factors that affect epidemics: (1) population size, (2) birth rate, (3) immigration rate, (4) number of susceptibles, (5) transmission rate, (6) death rate, and (7) immune rate.

The arrows that connect the boxed groups represent movement of people from one group to an adjacent one. New susceptibles enter the population by birth or immigration. Infected people are the source of the virus that infects new susceptibles; they either result from infection of susceptibles or immigration.

This scheme is a simplified representation of the dynamics or ecology of a virus epidemic. It is possible to develop mathematical models to describe or predict the course of an epidemic if the rates of movement through the scheme can be determined. One of the applications of the field of epidemiology is to determine these rates.

The Transmission Rate The arrow in Figure 2-1 that connects the susceptibles to the infected group (labeled 5) is the transmission rate of infection. This rate represents the

efficiency with which disease is transmitted from an infected person to a susceptible person. This transmission rate has two major components (Figure 2- 2). One is the inherent efficiency with which a particular virus can infect a susceptible person. The inherent efficiency of infection for a virus is dependent on the biological properties of the virus and the route by which the virus enters the susceptible person. For example, influenza virus, like many other viruses that infect the respiratory tract, has a high inherent efficiency of infection and is highly contagious. Respiratory viruses are easily taken up by breathing in aerosols (e.g., sneezes); once influenza virus comes into contact with cells of the respiratory tract, it readily infects them. HIV, on the other hand, actually has a relatively poor inherent infection efficiency, as we shall see later.

Figure 2-2 Transmission rate of infections (factor 5 in Figure 2-1) has two major components: (1) inherent efficiency of virus infection and (2) encounter rate between infected and uninfected.

It should be noted that if an infectious agent has more than one mode of infection, the inherent efficiency of infection may be different for each mode. An extreme example of this is the bacterium that causes the plague (see later in this chapter). The plague bacterium is typically spread by flea bites, resulting in the bubonic form of plague—in bubonic plague, infection mostly involves the lymph nodes inside the body. On the other hand, if the same bacterium infects the lungs, it can be directly transmitted from infected to uninfected people by coughing (the pneumonic form); this pattern of spread has a much higher inherent efficiency of infection.

The other major component of the transmission rate is the rate at which a susceptible person in the population encounters an infectious person—the encounter rate. Each encounter between an infected person and an uninfected person increases the likelihood that an infection will be transmitted.

As we shall see later with the AIDS virus, both of these components of transmission can be changed by altering the behavior of susceptible and infected persons. Behaviors that allow high encounter rates with infected people or that allow more efficient infection will favor the spread of an epidemic. Conversely, changes in behavior that reduce these transmission factors may control the spread of an epidemic.

Population Densities and Infections Many of the epidemics that have plagued humankind for the last few thousand years would not have had a favorable transmission rate during early human civilization. Early human societies were not urban but consisted of hunter– gatherers who lived in relatively small groups such as extended families. Such small groups or populations may not be able to produce new susceptibles in high enough numbers at any given time to support the continued growth and spread of disease-causing microorganisms. An acute disease produces symptoms and makes a person infectious soon after infection. The infected person transmits the disease, dies from the infection, or recovers and becomes immune to subsequent infections. An acute microorganism that strikes such small groups quickly infects all available susceptibles and then dies out.

About 10,000 years ago, the agricultural revolution allowed human populations to become large enough to support epidemics. In other words, the development of complex human societies was necessary before epidemics by acute viruses occurred. When the world population became sufficiently large, different patterns of infection also could develop. Acute epidemic diseases and agents could establish an endemic pattern—one in which the infectious disease is always present in some members of the large population. After the initial introduction and spread into a susceptible or naïve population, even a very lethal virus can become endemic. For endemic viruses, the numbers who are actively infected in the population are much lower, but they are always present. They serve as a source of infection for susceptibles. Endemic viral infections are often considered childhood diseases because the virus is so common in the population that most individuals encounter it during childhood. Most adults have been infected (with or without symptoms), and they have survived and are immune. Endemic viral infections may also have contributed to the high infant mortality in previous times (e.g., Europe in the Dark and Middle Ages) and in some developing countries today.

Endemic infectious agents can limit population sizes and result in populations that are relatively unaffected or are resistant to the infectious agent as a whole. As we shall discuss, when two previously separated societies encounter each other for the first time, the introduction of an endemic infectious agent into a population that has not previously encountered it (a naïve population) can have drastic results.

Chronic Infections

In addition to acute infections, such as measles, there are chronic infections. In acute infections, the disease symptoms generally occur quite soon after infection, and the infectious agent is generally eliminated by the individual’s immune system after the initial disease period. Some people infected with an acute virus do not develop symptoms (subclinical infections); nevertheless, they will generally eliminate the virus. In a chronic infection, the person does not eradicate the infectious agent (often a virus). The virus persists in the infected person, sometimes at low levels. People with chronic infections often do not show symptoms or disease immediately after infection. The differences between acute infection and chronic infection in an infected individual are diagrammed in Figure 2-3. As described earlier, acute infections generally require large populations (with continued new susceptibles) to be maintained. In contrast, chronic infections can sometimes be maintained in small populations. In addition, chronic infections are often more difficult to control at the population level because infected and uninfected people may be indistinguishable. Moreover, in persistent infections, the infected individual has not mounted an effective immune response to eliminate the virus. As we shall see, the syphilis epidemic was difficult to control partly because it is a chronic infection. Like syphilis, AIDS results from a chronic infection.

Figure 2-3 Acute versus chronic infection. These charts present the consequences of infection by an acute virus compared with infection by a chronic virus. The frequencies with which death, immunity, or continued infection occur are different for different viruses.

Controlling Infectious Diseases Since the beginning of the twentieth century, there has been a steady and dramatic decrease in the number of people who die from infectious diseases, particularly in developed countries. Recently, most developed countries have been free of major lethal contagious diseases. Antibiotics can kill bacterial infections after they start. Viruses pose a different problem: They are difficult to eliminate once they become established. Therefore, viral diseases have been controlled mostly by vaccination but occasionally by other measures. A vaccine induces immunity to a virus in susceptible individuals without the individuals becoming infected (Figure 2-4). Because birth is the major source of susceptibles in a population, in many cases, newborns are vaccinated. In fact, if enough (but not necessarily all) susceptibles are immunized, this can confer immunity on the population as a whole—a phenomenon called herd immunity. This is because an infected individual will most likely encounter only immunized individuals, so infection will not spread beyond that person. Thus it is possible to completely eliminate some infectious diseases from the human population with an effective vaccination program, even if not everyone is vaccinated. The smallpox virus, which was responsible for so much human death in historic times, is now eradicated from the general population because of successful worldwide vaccination efforts. A current target for similar eradication is poliovirus.

Figure 2-4 Epidemic control by vaccination.

A History of Epidemics

The Old World Even the very earliest historic records document the major impact of epidemics. It is not always clear to us now which infectious agent was causing a particular epidemic in ancient times, but we can often make guesses from the recorded symptoms. The three disease agents that have probably caused most human deaths are smallpox virus, measles virus, and plague bacterium (Yersinia pestis). These

three diseases have accounted for hundreds of millions of human deaths over the years and an unfathomable amount of human suffering. Other important epidemic agents include influenza virus, typhoid fever bacterium, yellow fever virus, polio virus, and, more recently, hepatitis viruses. The syphilis bacterium Treponema pallidum is of special interest here because of its sexual mode of transmission and its associated social problems.

Many historic accounts make clear reference to a supposed religious or moral reason for a particular epidemic. The transmission of disease itself was often believed to occur through casting of an evil eye. In the book of Exodus in the Old Testament, for example, God punished the Egyptian pharaoh for enslaving the Israelites by bringing upon Egypt a plague of “sores that break into pustules.” Epidemics were often perceived as punishment due to the wrath of a deity, perhaps for some offense by the entire population. Those who developed a disease were viewed as deserving it. This tendency to link a disease to social stigmatism has persisted throughout history and afflicts people with AIDS today.

The Greek writings are probably the earliest accounts in sufficient detail to allow us to measure the impact of epidemic disease. Aside from malaria, the Greeks were relatively free of most infectious diseases with one important exception. In 430–429 bce, an epidemic that may have been measles struck Athens with a devastating loss of life. It also resulted in a significant decrease in the size of its armies, and the following year Athens lost a war with Sparta. Thus, this epidemic may have influenced Greek history.

The Roman Empire also suffered massive epidemics in 165 ad and again in 251 ad. Before the 165 ad epidemic, the population of the Roman Empire was probably at its peak (about 54 million). After the 165 ad and 251 ad epidemics, the Roman population did not recover its size until modern times. The first epidemic could have been smallpox and appears to have killed one-third of Rome’s population. The 251 ad epidemic may have been measles and was equally devastating. There were about 5,000 deaths per day in Rome at the epidemic’s peak. Rome’s rural population may have been even more affected. This die-off may have led to the depopulation of agricultural lands and an inability to oppose invasion from the north. A third massive epidemic occurred in 542–543 ad, probably due to bubonic plague. Soon after this plague, Rome’s armies fell to the Visigoth and then to the Muslim armies, and the Dark Ages of Europe began. Thus, epidemiological history suggests that infectious diseases may have contributed to the fall of the Roman Empire.

The situation for China, although more difficult to estimate, appears to have been similar. Massive epidemics in 162 ad and again in 310 ad may account for much of the population decline in China, which peaked at about 50 million at

those times but declined to about 8.9 million by 742 ad. In Europe, and probably also in China, measles and smallpox eventually

became endemic childhood diseases after these devastating epidemics. In the following millennium, Europe experienced devastating epidemics from the disease known as the black death. Black death was a pneumonic (or lung infection) form of plague, which had a very high fatality rate. It probably accounted for up to 100 million deaths in Europe. The worst of these epidemics occurred in 1346. This epidemic appears to have been a pandemic, meaning that other continents (China and India) also were involved. The black death recurred in Europe in the 1360s and again in the 1370s. The seemingly arbitrary pattern of death and the massive suffering had dark social consequences for Europe. Xenophobia, the fear of foreigners, became common. Violent riots against Jews and Gypsies occurred in numerous cities because they were blamed as sources of the plague. Self-flagellation became a common practice, and rational theology lost popular acceptance. The situation improved somewhat in the 1400s. Black death became endemic, possibly because of selection for a less virulent plague bacterium; selection for people with greater resistance to the disease also may have occurred. European society was now experiencing most of these acute infectious diseases, especially the viral diseases, as childhood diseases.

The New World A well-documented example of what happens when a new viral disease enters a naïve population (one that has never encountered the virus) occurred when Spanish conquistador Hernán Cortés went to Mexico and introduced smallpox into the New World. The Aztec Codices (hieroglyphic-like records) tell us that the New World was relatively free of major infectious disease at that time. The population of Mexico was probably 25–30 million, and Mexico City may then have been the most populous city in the world. In 1518, just as the Aztecs drove Cortés from Mexico City, a smallpox epidemic swept through the city, killing the Aztec leaders and decimating the city’s population. This epidemic was followed by numerous other diseases that were European endemic childhood diseases but were devastating to the Aztecs. Within 50 years, the population of Mexico was down to about 1.5 million, or about 5% of what it had been at its peak. Furthermore, the fact that the diseases seemed to strike only the Aztecs and not the Spaniards led the Aztecs to believe that the gods favored the Spaniards.

Other American natives fared even worse than the Aztecs: The Native Americans of Baja, California, and other island tribes became totally extinct. Thus, the main fabric of native American society was utterly destroyed. Mexico

began to recover from this population loss only in the 1800s, and only now has Mexico City become one of the most populous cities in the world again. A similar fate was in store for the Pacific island natives, who also suffered huge population losses after encountering European explorers. Thus, throughout human history, infectious diseases have profoundly affected human populations.

Modern Concepts of Infectious Disease and Koch’s Postulates

The germ theory of disease—the idea that a microorganism or “germ” causes an infectious disease—was first proposed in 1546 by Girolamo Fracastoro, a Franciscan monk. However, it was not until the 1840s that Friedrich Henle, a German physician, clarified these concepts and they became accepted among scientists. One of Henle’s students, Robert Koch, subsequently proposed four postulates that could be used to prove that an infectious agent causes a disease. This was a milestone in the understanding of infectious disease. Koch’s postulates state that a microorganism can be considered to cause a disease if it fulfills the following criteria:

1. The microorganism is always found in diseased individuals. 2. The microorganism can be isolated from a diseased individual and grown

pure in culture. 3. The pure culture will initiate and reproduce the disease when introduced

back into a susceptible host (either human or animal). 4. The microorganism can be reisolated from that diseased individual.