MICROBIAL THREATS TO HEALTH

NATIONAL ACADEMIES PRESS

Contents

LIST OF FIGURES, TABLES, AND BOXES.....................................................................xxiACRONYMS...............................................................................................xxvEXECUTIVE SUMMARY......................................................................................11 INTRODUCTION.........................................................................................192 SPECTRUM OF MICROBIAL THREATS........................................................................23The Global Burden of AIDS, Tuberculosis, and Malaria...................................................25Emerging Infectious Diseases...........................................................................32Antimicrobial-Resistant Infections.....................................................................32Chronic Diseases with Infectious Etiology..............................................................41Microbes Intentionally Used for Harm...................................................................463 FACTORS IN EMERGENCE.................................................................................53Microbial Adaptation and Change........................................................................53Human Susceptibility to Infection......................................................................60Climate and Weather....................................................................................64Changing Ecosystems....................................................................................67Economic Development and Land Use......................................................................75Human Demographics and Behavior........................................................................78Technology and Industry................................................................................88International Travel and Commerce......................................................................97Breakdown of Public Health Measures....................................................................107Poverty and Social Inequality..........................................................................121War and Famine.........................................................................................125Lack of Political Will.................................................................................127Intent to Harm.........................................................................................130A Case in Point: Influenza-We Are Unprepared...........................................................1364 ADDRESSING THE THREATS: CONCLUSIONS AND RECOMMENDATIONS..............................................149Enhancing Global Response Capacity.....................................................................149Improving Global Infectious Disease Surveillance.......................................................154Rebuilding Domestic Public Health Capacity.............................................................159Improving Domestic Surveillance Through Better Disease Reporting.......................................163Exploring Innovative Systems of Surveillance...........................................................170Developing and Using Diagnostics.......................................................................174Educating and Training the Microbial Threat Workforce..................................................181Vaccine Development and Production.....................................................................184Need for New Antimicrobial Drugs.......................................................................190Inappropriate Use of Antimicrobials....................................................................204Vector-borne and Zoonotic Disease Control..............................................................209Comprehensive Infectious Disease Research Agenda.......................................................220Interdisciplinary Infectious Disease Centers...........................................................222EPILOGUE...............................................................................................227GLOSSARY...............................................................................................231REFERENCES.............................................................................................241APPENDIXESA Microbial Threats to Health Public Committee Meeting Agendas.........................................277B Syndromic Surveillance...............................................................................281C Pathogen Discovery, Detection, and Diagnostics.......................................................313D Forum on Emerging Infections Membership and Publications, Board on Global Health.....................331E Computational Modeling and Simulation of Epidemic Infectious Diseases................................335F Committee and Staff Biographies......................................................................343INDEX..................................................................................................353

Chapter One

Microbes live in every conceivable ecological niche on the planet and have inhabited the earth for many hundreds of millions of years. Indeed, microbes may be the most abundant life form by mass, and they are highly adaptable to external forces. The vast majority of microbes are essential to human, animal, and plant life. Occasionally, however, a microbe is identified as a pathogen because it causes an acute infectious disease or triggers a pathway to chronic diseases, including some cancers. Certainly, humankind remains ignorant of the full scope of diseases caused by microbial threats, as only a small portion of all microbes have been identified by currently available technologies.

Microbial threats continue to emerge, reemerge, and persist. Some microbes cause newly recognized diseases in humans; others are previously known pathogens that are infecting new or larger population groups or spreading into new geographic areas. Within the last 10 years, newly discovered infectious diseases have emerged in the United States (e.g., hantavirus pulmonary syndrome from Sin Nombre virus) and abroad (e.g., viral encephalitis from Nipah virus). During the same time, the worldwide resurgence of long-recognized infectious diseases (e.g., tuberculosis, malaria, cholera, and dengue) has gained in force. The United States has seen the importation of infectious diseases, such as West Nile encephalitis, measles, multidrug-resistant tuberculosis, malaria, and cyclosporiasis, from immigrants, U.S. residents returning from foreign destinations, and products of international commerce.

The realization of just how quickly newly discovered infectious diseases can spread has generated a heightened appreciation of the inherent dangers of microbial pathogens. Acquired immunodeficiency syndrome (AIDS) has become the fourth-leading cause of death worldwide in a mere 20 years since its discovery. Today, more than 40 million people are living with infection from the human immunodeficiency virus (HIV), and 20 million people have died from AIDS. In just 3 years since West Nile virus was discovered in the Western Hemisphere, the virus has spread from its epicenter in New York to 39 states (including California), infecting thousands and killing hundreds.

The emergence and spread of microbial threats are driven by a complex set of factors, the convergence of which can lead to consequences of disease much greater than any single factor might suggest. Genetic and biological factors allow microbes to adapt and change, and can make humans more or less susceptible to infections. Changes in the physical environment can impact on the ecology of vectors and animal reservoirs, the transmissibility of microbes, and the activities of humans that expose them to certain threats. Human behavior, both individual and collective, is perhaps the most complex factor in the emergence of disease. Emergence is especially complicated by social, political, and economic factors-including the development of megacities, the disruption of global ecosystems, the expansion of international travel and commerce, and poverty-which ensure that infectious diseases will continue to plague us. Today we also face the threats of intentionally introduced biological agents. The risks to humankind from the willful spread of highly virulent and contagious microbes are considerable, and we in the United States are preparing to defend ourselves with new vaccines, diagnostics, and therapeutics against the many microbes that might be used in a biological attack. We also are cognizant of the need to rebuild public health infrastructure locally and globally as an indispensable means of reacting to such threats.

Can a focus on naturally occurring microbial threats be maintained in the face of expanded efforts to contain the threat of intentional biological attacks? Some may ask which is the greater risk-the intentional use of a microbial agent to cause sudden, massive, and devastating epidemics of disease, or the continued emergence and spread of natural diseases such as tuberculosis, AIDS, malaria, influenza, and multidrug-resistant bacterial infections. It is a tragic reality that hundreds of people die from naturally occurring infections every hour, whereas until now, intentional biological attacks on a major scale have remained a theoretical risk, rife with political as well as technical uncertainties. HIV/AIDS has taught us the importance of remaining vigilant to the devastation of naturally arising epidemics, which can have profound effects not only on individuals, but also on whole nations and regions. The economic and social disruption that often follows an infectious disease outbreak and typically accompanies the persistent burden due to endemic infectious diseases can be a major destabilizing force for any nation. The challenge is to keep our concerns and responses in reasonable balance. This report contains prescriptions for acting wisely to integrate our surveillance, control, and prevention efforts aimed at natural scourges with enhanced security from intentional biological attacks.

Throughout history, humans have struggled to control both the causes and the consequences of infectious diseases, and we will continue to do so into the foreseeable future. Disease control for many pathogens includes vaccines and pharmaceuticals, but how long these controls will remain effective or even available is uncertain. We appear less able (or willing) to develop new antimicrobials and vaccines than once was the case, especially for infectious diseases that affect developing countries disproportionately. A variety of technical, political, social, and economic issues challenge our ability to develop and deploy new antimicrobials and vaccines. The burden of infectious diseases has become further compounded as resistance to vector-control agents and antimicrobials has grown pervasive not only in the United States, but also worldwide.

The 1992 Institute of Medicine report Emerging Infections: Microbial Threats to Health in the United States took a fresh look at the impact of new and reemerging infectious diseases on the United States. In 2001, the Committee on Emerging Microbial Threats to Health in the 21st Century was charged to identify, review, and assess the current state of knowledge regarding factors in the emergence of infectious diseases; to assess the capacity of the United States to respond to emerging microbial threats to health; and to identify potential challenges and opportunities for domestic and international public health actions to strengthen the detection and prevention of, and response to, microbial threats to human health. The committee acknowledges that infectious diseases in animals and agriculture have indirect effects on human health (e.g., reductions in available food sources, economic and psychological hardships for food-animal producers due to culling), and are an important component of the overall assessment of infectious disease response and control. The scope of this report, however, was limited to infectious diseases in humans.

SPECTRUM OF MICROBIAL THREATS

The spectrum of microbial threats is a continuum that comprises the emergence of newly recognized infectious diseases, the resurgence of endemic diseases, the appearance of new antimicrobial-resistant forms of diseases, the recognition of the infectious etiology of chronic diseases, and the intentional use of biological agents for harm.

FACTORS IN EMERGENCE

The convergence of any number of factors can create an environment in which infectious diseases can emerge and become rooted in society. A model was developed to illustrate how the convergence of factors in four domains impacts on the human-microbe interaction and results in infectious disease (see Figure ES-1). Ultimately, the emergence of a microbial threat derives from the convergence of (1) genetic and biological factors; (2) physical environmental factors; (3) ecological factors; and (4) social, political, and economic factors. As individual factors are examined, each can be envisioned as belonging to one or more of these four domains. The following individual factors in emergence are examined in this report:

Microbial adaptation and change. Microbes are continually undergoing adaptive evolution under selective pressures for perpetuation. Through structural and functional genetic changes, they can bypass the human immune system and infect human cells. The tremendous evolutionary potential of microbes makes them adept at developing resistance to even the most potent drug therapies and complicates attempts at creating effective vaccines.

Human susceptibility to infection. The human body has evolved with an abundance of physical, cellular, and molecular barriers that protect it from microbial infection. Susceptibility to infection can result when normal defense mechanisms are altered or when host immunity is otherwise impaired by such factors as genetically inherited traits and malnutrition.

Climate and weather. Many infectious diseases either are strongly influenced by short-term weather conditions or display a seasonality indicating the possible influence of longer-term climatic changes. Climate can directly impact disease transmission through its effects on the replication and movement (perhaps evolution) of pathogens and vectors; climate can also operate indirectly through its impacts on ecology and/or human behavior.

Changing ecosystems. In general, changes in the environment tend to have the greatest influence on the transmission of microbial agents that are waterborne, airborne, foodborne, or vector-borne, or that have an animal reservoir. Given today's rapid pace of ecological change, understanding how environmental factors are affecting the emergence of infectious diseases has assumed an added urgency.

Economic development and land use. Economic development activities can have intended or unintended impacts on the environment, resulting in ecological changes that can alter the replication and transmission patterns of pathogens. A growing number of emerging infectious diseases arise from increased human contact with animal reservoirs as a result of changing land use patterns.

Human demographics and behavior. An infectious disease can result from a behavior that increases an individual's risk of exposure to a pathogen, or from the increased probability of exchange of a communicable infectious disease between humans as the world's population increases in absolute number. Additional factors include demographic changes such as urbanization and the growth of megacities; the aging of the world's population and the associated increased risk of infection; and the growing number of individuals immunocompromised by cancer chemotherapy, chronic diseases, or infection with HIV.

Technology and industry. Infectious diseases have emerged as a direct result of changes in technology and industry. Advances in medical technologies, such as blood transfusions, human organ and tissue transplants, and xenotransplantation (using an animal source), have created new pathways for the spread of certain infections. Even the manner in which animals are raised as food products, such as the use of antimicrobials for growth production, has abetted the rise in infectious diseases by contributing to antimicrobial resistance.

International travel and commerce. The rapid transport of humans, animals, foods, and other goods through international travel and commerce can lead to the broad dissemination of pathogens and their vectors throughout the world. Microbes that can colonize without causing symptoms (e.g., Neisseria meningitidis) or can infect and be transmissible at a time when infection is asymptomatic (e.g., HIV, hepatitis B, and hepatitis C) can spread easily in the absence of recognition in traveling or migrant hosts. Pathogens in meat and poultry, such as the agents of "mad cow disease," can also be delivered unintentionally across borders, while the vectors of tropical diseases can be transported in cargo holds or in the wheel wells of international aircraft.

Breakdown of public health measures. A breakdown or absence of public health measures-especially a lack of potable water, unsanitary conditions, and poor hygiene-has had a dramatic effect on the emergence and persistence of infectious diseases throughout the world. The breakdown of public health measures in the United States has resulted in an increase in nosocomial infections, difficulties in maintaining adequate supplies of vaccines in recent years, immunization rates that are far below national targets for many population groups (e.g., influenza and pneumococcal immunizations in adults), and a paucity of needed expertise in vector control for diseases such as West Nile encephalitis.

Poverty and social inequality. At the same time that infectious diseases have significant and far-reaching economic implications, social inequality, driven in large part by poverty, is a major factor in emergence. Mortality from infectious diseases is closely correlated with transnational inequalities in income. Global economic trends affect not only the personal circumstances of those at risk for infection, but also the structure and availability of public health institutions necessary to reduce risks.

War and famine. War and famine are closely linked to each other and to the spread of infectious diseases. Displacement due to war and the fairly consistent sequelae of malnutrition due to famine can contribute significantly to the emergence and spread of infectious diseases such as malaria, cholera, and tuberculosis.

Lack of political will. If progress is to be made toward the control of infectious diseases, the political will to do so must encompass not only governments in the regions of highest disease prevalence, but also corporations, officials, health professionals, and citizens of affluent regions who ultimately share the same global microbial landscape. The complacency toward the threat of infectious diseases that has become somewhat entrenched in developed countries must reverse in direction if we are to avoid losing windows of opportunity to reduce the global burden of infection.

Intent to harm. The world today is vulnerable to the threat of intentional biological attacks, and the likelihood of such an event is high. The U.S. public health system and health care providers should be prepared to address various biological agents that pose a risk to national security because of their potential to cause large numbers of deaths and widespread social disruption.

Recognizing and addressing the ways in which the factors in emergence converge to change vulnerability to infectious diseases is essential to the development and implementation of effective prevention and control strategies. Detecting and responding to global infectious disease threats is in the economic, humanitarian, and national security interests of the United States and essential to the health of its people.

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