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Emerging Infectious Diseases: Concepts

in Preparing for and Responding

to the Next Microbial Threat

Shantini D. Gamage, Stephen M. Kralovic, and Gary A. Roselle

INTRODUCTION

Former U.S. Surgeon General William H. Stewart has been attributed with stating in the late 1960s that the time had come to “close the book” on infectious diseases as major threats to public health. Even though the statement’s authenticity has been called into question, it is often used to convey the optimism widely expressed at the time by health experts and world lead- ers. Indeed, it did appear that the age of infectious diseases that had plagued humans for millennia was coming to an end. Vac- cines and antibiotics had substantially reduced the incidence and mortality of many diseases. The smallpox eradication campaign was on its way and it was thought that eradication of other dis- eases (for example tuberculosis and polio) would not be too far behind. Improved food and water safety resulted in less exposure to disease-causing microbes, and the use of pesticides to con- trol arthropod populations had reduced vector-borne diseases. It seemed the battle with the microbial world had been won and it was time to focus efforts and funding on the looming threat of chronic diseases.

Of course, this confidence largely ignored the burden of infectious diseases in the developing world. Four decades later, although great strides have been made to control infectious dis- eases, microbial pathogens are still major threats to public health throughout the world. The last few decades have ushered in new challenges: “old” pathogens once thought to be controlled by antibiotics have developed multidrug resistance, new pathogens have emerged, and traditional pathogens have appeared in new places. Furthermore, factors such as increased global commerce and travel, and the threat of the intentional release of pathogens have set the stage for infectious disease disasters with large numbers of casualties. In this chapter, “casualties” includes all persons with symptoms of the infectious disease, not just fatalities.

There is a wide body of knowledge on the emergence and reemergence of pathogens of public health importance. It is now clear that humans are in a delicate balance with microbial cohab- itants of the earth; circumstances can tip that balance in favor of microbes with new or renewed pathogenic vigor. There will always be emerging pathogens, and consequently there is always

the chance that a virulent microbe will cause extensive human disease and death. Exactly what the causative agent of the next big infectious disease disaster will be and when it will happen is not known. Using examples from past events, this chapter addresses the concepts and tools necessary to prepare better for and respond to infectious diseases disasters in general.

OVERVIEW

The Threat of Emerging Infectious Diseases

Infectious diseases are caused by microorganisms such as bacte- ria, viruses, fungi, and protozoa, and by proteinaceous particles called prions. The majority of microbes on earth are benign to humans; many are necessary for ecological stability, and even human and animal health. Microbes that do cause disease are collectively referred to as pathogens. There are more than 1,400 pathogens known to cause disease in humans.1

Some pathogens are prevalent at a constant and stable rate in a given population and are considered “endemic” (see Table 6.1 for a list of definitions). Other infectious diseases are not com- mon to a given population but, at times, a number of cases occur that is higher than expected. This situation is considered an “outbreak” (for a more localized increase in disease incidence) or an “epidemic” (for a larger regional increase in disease inci- dence). The concept of the epidemiological triangle (Figure 6.1) is used to understand the factors involved in promoting such an outbreak or epidemic. This model highlights the interactions among an agent (e.g., Salmonella), a host (e.g., elderly patients at a nursing home), and an environment (e.g., undercooked chicken left at room temperature) that cause disease (e.g., acute gastro- enteritis).

Many pathogenic microbes have been associated with human disease for hundreds or thousands of years. Examples of infec- tious diseases with long human histories include smallpox, plague, cholera, malaria, tuberculosis, and syphilis. These dis- eases, and others, resulted in millions of deaths over the centuries and were the focus of targeted efforts to reduce the burden of infectious diseases on human populations. Improvements to public health systems, such as sanitation and education,

75 Koenig and Schultz's Disaster Medicine : Comprehensive Principles and Practices, edited by Kristi L. Koenig, and Carl H. Schultz, Cambridge University Press, 2009. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/apus/detail.action?docID=564432. Created from apus on 2018-03-08 12:21:14.

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Table 6.1: Definition of termsa

Description Example

Airborne transmission The process whereby agents are spread by small-particle (≤5 µm) droplet nuclei that can suspend in the air and travel by air currents or through ventilation systems; respiratory PPE (N95 respirator) is often required to prevent infection in responders.

Mycobacterium tuberculosis

Biological Incident The presence of a pathogen in a population from a natural, accidental, or intentional exposure that has the potential to cause extensive public harm and/or fear.

2003 SARS epidemic in Toronto (natural); 1979 atmospheric release of anthrax spores in Sverdlovsk, USSR (accidental); 2001 dissemination of anthrax spores in U.S. mail (intentional)

Communicable The ability of an infectious agent to be transmitted from one host to another; contagious.

Influenza, smallpox

Contact transmission The process whereby agents are spread by direct contact with a person or indirect contact with contaminated objects.

Direct contact: skin (MRSA); mucous membrane (HIV)

Indirect contact: fecal-oral (norovirus)

Droplet transmission The process whereby agents are spread by large-particle (> 5µm) droplet nuclei produced by, for example, coughing and sneezing; agent does not remain suspended in the air for a long time and infection usually occurs when susceptible person is within 1 m of infected person. A surgical mask may offer protection.

Influenza virus

Endemic A disease that is consistently present in a population at a certain level or rate without requiring introduction from another area.

Malaria in India and Africa

Epidemic A level of disease that is higher than the expected level at a time or location. Similar to an “outbreak” but usually refers to disease incidence that spans a large region, country, or multiple countries for a prolonged period of time.

Diphtheria in Russia

Host – Resistant The state in which a person is immune to infection by a specific pathogen.

In general, a person who has had chickenpox is resistant to subsequent infection with the chickenpox virus

Host – Susceptible The state in which a person can be infected by a specific pathogen. May be due to lack of immunity and/or to host factors that promote infection (e.g., a specific receptor).

A person who has not had the Measles/Mumps/Rubella (MMR) vaccine is susceptible to the agents that cause these diseases

Isolation The separation of infectious disease cases from the general population to prevent transmission of the agent to susceptible people; instead of physical separation, may use barriers such as masks on cases to “isolate” the infection and prevent transmission (this may be necessary in disasters with many casualties).

SARS cases were sequestered on specific hospital wards

Mode of Transmission The mechanism a pathogen uses to spread from one host to another.

Airborne transmission by small particles in the air

Outbreak An increased incidence of a disease in a region. Usually on a smaller scale (regionally and temporally) than an epidemic.

A food-borne outbreak typically refers to disease caused by food(s) contaminated with a specific pathogenic microorganism.

Neisseria meningitidis outbreak on a college campus

Pandemic The global spread of an epidemic. 1918 Influenza pandemic

Quarantine The restriction of movements of healthy people who were exposed to a contagious agent to prevent contact with the general public. The duration of the quarantine period is usually the longest time for symptoms to appear after exposure (incubation time). Work quarantine refers to permitting exposed healthcare workers and emergency responders to go to work using appropriate PPE so that disaster operations can remain intact; this modification does not apply to workers in the general public.

In Ontario, Canada in 2003, people who were exposed to SARS were quarantined for 10 days. At times during the epidemic, over half of the paramedics in the Toronto area were operating under work quarantine conditions

Koenig and Schultz's Disaster Medicine : Comprehensive Principles and Practices, edited by Kristi L. Koenig, and Carl H. Schultz, Cambridge University Press, 2009. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/apus/detail.action?docID=564432. Created from apus on 2018-03-08 12:21:14.

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EM E RG I N G IN F E C T I O U S DI S E A S E S ■ 77

Description Example

Reservoir The environmental niche of a pathogenic organism, usually another organism unaffected by the infectious agent

Specific rodent species are the reservoirs for particular hantavirus strains

Transmission rate (R0) For an infectious agent, the number of people to whom an infected person spreads the disease in the absence of control measures (such as vaccination, isolation of cases).

According to historical data, a person with pandemic influenza will transmit the disease to 3 other people

Vector An organism (e.g., insects or other arthropods) that harbors and transfers agents that are pathogenic to another organism (e.g., humans).

Ixodes ticks transfer Borrelia burgdorferi, the causative agent of Lyme disease, to humans; Anopheles mosquitoes transfer Plasmodium sp, the causative agents of malaria, to humans

Zoonoses Infectious diseases in which the pathogenic agent is transmitted to humans from animals.

West Nile virus encephalitis is transmitted to humans from birds (via the mosquito vector)

a Terms are defined as they pertain to infectious diseases biology.

reduced human contact with pathogens. Scientific advances, such as antibiotics and vaccines to treat and prevent infectious diseases, revolutionized the medical arsenal against microbes. As a result, by the middle of the twentieth century, the inci- dence of many infectious diseases plummeted, particularly in the developed world. It was widely thought that science had conquered the threat that infectious diseases posed to human health.

What is appreciated now is that microbes are constantly interacting with their environment and evolving. As they do, circumstances may allow for the emergence of new infectious agents/diseases, or the reemergence of previously controlled con- tagions. These emergences fall into many categories:2

Figure 6.1. The epidemiological triangle. This type of diagram is widely used to represent the interconnectedness of the three major components involved in the emergence of infectious diseases. The “Host” is the organism that is affected by the pathogen or toxin and can develop disease. The “Agent” is the infectious microorganism (pathogen) or toxin. The “Environment” refers to the circumstances that influence the interaction between the Host and the Agent. Exam- ples of influencing factors are given for each component.

■ Microorganisms that have not been known previously and that cause new diseases (e.g., severe acute respiratory syn- drome coronavirus [SARS-Cov]; human immunodeficiency virus [HIV] that causes acquired immunodeficiency syn- drome [AIDS]);

■ Agents that have been known previously and that cause new diseases (hantavirus in the U.S. in 1993 that caused respira- tory distress instead of kidney disease);

■ Microbes that have been known previously to cause disease, but the incidence of disease is noticeably increasing in a region (e.g., whooping cough caused by Bordetella pertussis in the U.S.; diphtheria caused by Corynebacterium diphtheriae in Russia);

■ New, and often more virulent, strains of a known pathogen that cause disease (e.g., Vibrio cholerae O139 and epi- demic diarrheal disease; highly virulent Clostridium difficile NAP1/027 and increased incidence of C. difficile-associated disease in North America and Europe). Increased virulence often occurs when a pathogen acquires a genetic element that allows for the production of a new virulence factor such as a toxin (e.g., Staphylococcus aureus that produces TSST-1 and causes toxic shock syndrome);

■ Microbial pathogens that cause disease in a new geograph- ical location (e.g., West Nile virus encephalitis in North America);

■ Microbes of animal origin that infect humans (zoonoses). This includes animal-associated microorganisms to which humans are newly exposed (e.g., hantavirus pulmonary syn- drome due to Sin Nombre virus from the rodent population in the U.S.), or animal-associated microbes that are newly able to infect humans (e.g., influenza virus from birds or swine);

■ Microbial pathogens that have acquired the ability to resist the antimicrobial effects of antibiotics (e.g., multidrug resis- tant tuberculosis [MDR-TB]; methicillin-resistant S. aureus).

The occurrence of emerging infectious diseases (EIDs) or reemerging infectious diseases in human history is not new. The great plague and influenza pandemics are well-known histor- ical examples. The last few decades have witnessed a recrudes- cence of EIDs. Furthermore, as global surveillance of diseases has

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78 ■ SH A N T I N I D. GA M AG E, ST E P H E N M. KR A LOV I C, A N D GA RY A. RO S E L L E

Figure 6.2. Emerging and reemerging infectious diseases/agents, 1990–2006. E. coli, Escherichia coli; vCJD, variant Creutzfeldt–Jakob disease; HIV, human immunodeficiency virus; SARS, severe acute respiratory syndrome. Adapted from the National Institutes of Health website (www3.niaid.nih.gov/about/overview/planningpriorities/strategicplan/emerge.htm).

developed, the awareness that new EIDs are occurring has increased. Although exact numbers of EIDs are debatable due to differences in criteria used, Taylor and colleagues suggest that 175 of the 1,400 plus known human pathogens are EIDs (approx- imately 12%).1 Figure 6.2 shows recent EIDs and reemerg- ing infectious diseases in both the developed and developing world.

The question then is: Why are EIDs occurring so frequently despite the optimism of past generations? In 2003, the Institute of Medicine (IOM) published Microbial Threats to Health: Emer- gence, Detection and Response,3 which outlined 13 factors that contribute to the emergence or reemergence of new pathogens (Table 6.2). The factors reflect a very different world from previ- ous decades – “globalization,” often characterized by changes in global movement, economic development, and environmental and agricultural practices – has unwittingly exposed the world’s populations to microbial threats. Not all of the categories are nec- essary for every emerging pathogen; however, neither are they mutually exclusive. The emergence or reemergence of a pathogen is usually a function of many factors. An understanding of all the factors is necessary to prevent future EIDs and to determine how to effectively mitigate an EID disaster. Table 6.3 uses pandemic influenza, dengue hemorrhagic fever, multidrug resistant tuber- culosis, and AIDS to demonstrate how these factors interplay in the emergence or reemergence of diseases.

Many of the 13 factors outlined by the IOM drive disease emergence by influencing the interaction of humans with animal reservoirs of potential pathogens. In fact, approximately 75% of recently emerged pathogens are zoonotic, or transmitted from animals to humans. The abundance, location, and behaviors of putative animal reservoirs, and human influences on them, are important factors in disease emergence. Microbes often live in harmony with certain animal hosts and the pathogenic infection of humans is inadvertent.

Infectious Diseases and Disaster Medicine

History has shown that infectious disease outbreaks, epidemics, and pandemics have the potential to afflict large numbers of people. Estimates for the next severe influenza pandemic suggest millions of cases in the U.S. alone with hundreds of thousands of flu-related fatalities. The 2001 deliberate release of anthrax spores in the U.S. through the postal system and the 2003 SARS pandemic are reminders that the scope of the disaster is not just a function of actual case numbers, but of the ability to respond to the outbreak and to the public reaction during the event. Both situations taxed the available resources of some of the most sophisticated public health systems in the world despite relatively low numbers of cases.4,5

Disasters are commonly considered to be acute, often regional, events. Even in the realm of infectious diseases, the anthrax letters incident in the U.S. is often cited as an exam- ple of the type of response required for an infectious disease disaster. More likely, however, biological situations (of either intentional or unintentional origin) that strain response efforts will unfold in a more gradual manner. Furthermore, if disasters are defined as situations that require external resource assis- tance, then the global AIDS pandemic (now decades long) can be considered a disaster. Disasters due to EIDs are of particular concern given the paucity of information on the biology of the agent, the course of disease, and mechanisms of treatment. Even a local outbreak of a known infectious agent can strain a response effort.

Management of infectious disease disasters shares many gen- eral aspects of the management of other disasters. The basic principles of leadership and collaboration, resource manage- ment, surge capacity, triage and public relations are all important; however, the specifics of response activities can have special con- siderations when an infectious agent is the cause of the disaster.

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EM E RG I N G IN F E C T I O U S DI S E A S E S ■ 79

Table 6.2: Factors that Drive the Emergence or Reemergence of Infectious Diseases

Factor in Emergence Description Example

Microbial Adaptation Microbes are under constant selective pressure from the environment to adapt genetically for survival. Evidence of adaptation includes: the evolution or acquisition of antibiotic resistance genes that allow bacteria to survive exposure to antibiotics, the mutation of genetic material, and the horizontal transfer of virulence genes from one microbe to another.

The emergence of multidrug-resistant tuberculosis, which is resistant to at least two of the primary antibiotics used to treat disease. Even more alarming is the appearance of extensively drug-resistant tuberculosis (XDR-TB), resistant to many first-line and second-line antibiotics.

Human Susceptibility The ability to stave off a pathogenic infection is predominantly due to host immunity, a multiorgan system involving physical barriers, complex cell–cell signaling, recognition, and memory to fight invading pathogens. A healthy immune system is a function of many factors. The extremes of age, poor nutrition, and presence of chronic and/or infectious diseases could result in an immunocompromised state.

The increased incidence of Pneumocystis carinii pneumonia in the U.S. as the HIV/AIDS population increased.

Climate and Weather Changes in climate and weather affect every organism in a region. As plant and animal life is affected, so too is the interaction between humans and these organisms, and the microorganisms they may harbor. Climatic changes can also affect human activities. For example, a negative effect on crop production can increase malnutrition and render a population more susceptible to disease. Furthermore, agricultural practices may be altered, exposing populations to different vectors and microbial agents.

Certain species of zooplankton are associated with the presence of pathogenic Vibrio cholerae.a In South America, the El Niño southern oscillation of 1991–1992 increased coastal water temperatures, zooplankton density and, consequently, exposure of people to V. cholerae. The ensuing cholera epidemic was the first in the region in a century.

Changing Ecosystem The environment can have a profound impact on the emergence of pathogens, predominantly through wildlife ecology and the interaction of humans with the vectors and animals that carry potential pathogens. Environmental changes in forestation, humidity, and predator density due to natural or anthropogenic causes can all affect vector and pathogen biology.

Dam building in Ethiopia to improve agricultural productivity had the undesired side effect of increasing mosquito breeding grounds, an outcome implicated in increases in malaria cases in children.b

Human Demographics and Behavior

At over 6 billion people, the world population is four times as large as it was at the beginning of the 20th century when advances in science, medicine, and public health first allowed for the widespread control of infectious diseases. The increasing population has resulted in crowded living conditions and habitation of previously undeveloped areas, exposing more individuals to new diseases. Human behaviors, often for economic gain, can also influence disease emergence.

Live-animal markets that put humans and pathogens in close contact (e.g., SARS-CoV and influenza viruses). Commercial sex workers who engage in unprotected sexual intercourse (e.g., HIV emergence in Asia).

Economic Development and Land Use

Globalization of national economies has resulted in an unprecedented interdependence in trade and commerce, and an increase in the volume of goods produced. Land use for industry and agriculture, and for population expansion, can influence emerging diseases.

Widespread deforestation in Malaysia for the expansion of plantations encroached on the natural habitat of fruit bats, the reservoir for the previously unknown Nipah virus. The fruit bats found food in the orchards that were adjacent to swine farms and infected the swine with Nipah virus. In 1988, human disease emerged.

Technology and Industry Medical technology has improved lives, but also has led to an increase in immunocompromised persons (e.g., transplant recipients).

Technology has allowed for mass production in the food industry. Larger animal feedlots and processing plants facilitate the transmission of infectious agents from one animal to another. Refrigeration, packaging, and transportation networks allow foods from different regions and countries to be distributed throughout a nation.

Advanced water distribution systems for consumption, hygiene, recreation, and indoor temperature regulation are comforts particularly associated with and expected in the developed world. With this technology comes the risk of mass distribution of pathogens.

Hemophiliacs who were infected with HIV from infected blood products.

Spinach contaminated with E. coli O157:H7 affected people in over 25 states in the U.S. in 2006.

International Travel and Commerce

The movement of people across regions means the movement of microbes and vectors as well. In addition to traveling for pleasure or for business, people move across borders for temporary employment, as military personnel, as immigrants, as refugees, as undocumented persons, or in situations of forced labor.

Commerce is highly dependent on international production and trade of goods. For example, foods once considered exotic or seasonal are available in the U.S. year round due to importation from other countries.

One infected person spread the SARS-CoV from Guangdong Province, China to 12 guests at a Hong Kong hotel. The 12 people spread the virus to 5 other countries. In 6 months, the SARS-CoV spread from China to over 30 countries on 6 continents.

(continued)

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Table 6.2 (continued)

Factor in Emergence Description Example

Breakdown of Public Health Infrastructure

Public health measures, such as sanitation, health education, vaccinations, and access to care, are critical for preventing infectious diseases. These measures must be consistently upheld, or microbial pathogens will return to the niche they once inhabited. Reasons for public health inadequacies or collapse include economic hardship, political instability, war, complacency, disasters, and lack of priority standing.

In the early 1990s, diphtheria reemerged in the former Soviet Union amidst a turbulent political, economic, and social environment.

In 2000, approximately 2,300 people in Walkerton, Ontario, Canada became ill after consuming inadequately treated and monitored drinking water contaminated with E. coli O157:H7 and Campylobacter jejuni.

Poverty and Social Inequality

Increased populations, political unrest, and/or inadequate food production in some areas have resulted in increased numbers of persons who are malnourished and without access to medical care. Infectious disease outbreaks in these areas tax already overburdened healthcare systems. Inadequate resources spread disease by failing to reach the sick, transmitting the pathogen in the healthcare setting due to crowding and reusing supplies, and neglecting to educate the population on safe practices. In addition, the lack of adequate courses of medication leads to incomplete treatment of disease and the emergence of antibiotic-resistant pathogens.

The incidence of AIDS, malaria, and tuberculosis has reached alarming rates in developing countries where resources are scarce.

War and Famine War often unsettles populations and increases the reliance on public health infrastructures to provide medicines, food, and emotional support to affected persons. As noted above, these health systems are often inadequate during peacetime and cannot undertake additional responsibilities during unrest. Furthermore, poor health status in a population may result from 1) substandard housing in refugee camps, 2) guerilla-controlled access to food and medicines, 3) elevated pollution, and 4) interrupted power and water distribution. Infectious diseases can spread from contaminated food or water, from persons with contagious respiratory diseases, or from sexual assaults.c Famine, like poverty, deteriorates the health of populations and renders them more susceptible to old and new infectious diseases.

Cholera outbreaks in the 1990s among Rwandan refugees in the Democratic Republic of Congo resulted in thousands of deaths in weeks.d

Lack of Will Four segments of the global society that must commit to combating emerging infectious diseases are monetary donors, health professionals, governments, and patients and civil society. Donors, both private and public, are necessary to provide funding for research and for health programs; health professionals must be available to design and implement intervention and prevention programs; governments must prioritize infectious disease science, surveillance and reporting, build public health infrastructures, and collaborate with other nations and global partners; and the community needs to motivate the other segments to act by voicing concerns and participate in intervention and prevention programs.

In the West, early efforts to understand HIV and determine intervention strategies were stalled by political and societal discomfort that the disease was spreading in the homosexual male population.

Inadequate education on the myths and facts of sexually transmitted disease prevention led to widespread transmission of HIV through Africa and Asia.

Intent to Harm There is heightened awareness to the threat of an intentional attack with a bioweapon. In addition to the unpredictability of when and where such an attack will occur, the type of microbe that will be used is largely unknown. There is concern that an agent used will be one not regularly encountered in the afflicted area. In effect, a bioterrorist attack could result in the emergence or reemergence of infectious diseases in an area, with the potential to cause many casualties. In addition, the social, political, and economic disruption could be far-reaching.

2001 release of anthrax spores via the U.S. postal system.e

Source: Institute of Medicine. a Lobitz B, Beck L, Huq A, et al. Climate and infectious disease: use of remote sensing for detection of Vibrio cholerae by indirect measurement. Proc Natl

Acad Sci. 2000;97(4):1438–1443. b Ghebreyesus TA, Haile M, Witten KH, et al. Incidence of malaria among children living near dams in northern Ethiopia: community based incidence

survey. BMJ. 1999; 319(7211):663–666. c Tam CC, Lopman BA, Bornemisza O, Sondorp E. Epidemiology in conflict – a call to arms. Emerg Themes Epidemiol. 2004;1(1):5. d Connolly MA, Heymann DL. Deadly comrades: war and infectious diseases. Lancet. 2002;360(Suppl):s23–s24. e Institute of Medicine. Microbial Threats to Health: Emergence, Detection and Response. Washington, DC: National Academies Press; 2003.

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Table 6.3: Examples of How Multiple Factors Influence the Emergence or Reemergence of Infectious Diseases

Pandemic Influenza∗ (Highly Dengue Hemorrhagic Fever Multidrug-resistant Infectious Disease pathogenic avian influenza (Dengue virus; transmitted to Tuberculosis (Mycobacterium (Agent) [HPAI] virus) humans by mosquito vector) tuberculosis) AIDS (HIV)

Emergence Factor

Microbial Adaptation

Reassortment of or mutations in influenza virus genes that allow for human–human transmission of HPAI virus

Adaptation of viral strains to urban mosquitoes facilitated emergence

Improper usage of antibiotics allowed M. tuberculosis to develop resistances

Mutation of simian immunodeficiency virus to infect humans; emergence of drug-resistant HIV; high mutation rate complicates vaccine development

Human Susceptibility

Extensive viral adaptations means no inherent immunity in humans; no vaccine-enhanced immunity in the initial months of the pandemic

No cross-immunity to the 4 different viral strains; heterologous infection increases chance of severe disease

Increased tuberculosis in HIV-endemic areas

Lack of host immunity when virus emerged; no vaccine-enhanced immunity

Climate and Weather

Cold weather in some countries during flu season encourages social clustering and, consequently, viral transmission

Rainy seasons increase mosquito population

Changing Ecosystems

Changing marshland habitats and waterfowl distribution

Repopulation of New World by mosquito species after mid-20th century mosquito eradication programs endeda

Human Demographics and Behavior

Increased worldwide poultry production to feed increased human population; cohabitation with potential zoonotic sources

Disease centers in overpopulated urban areas with poor housing and utilities management that promote mosquito breeding grounds

Failure to adhere to medication regimens; people in remote areas hard to treat consistently; immigration of infected persons

Unprotected sexual activity; illicit intravenous drug use; prostitution

Economic Development and Land Use

Live markets put humans and infected birds in close contact

Dam building promotes mosquito breeding grounds

Technology and Industry

Crowded poultry feedlots favor viral transmission between birds

Possible disease transmission through blood products

Disease transmission through blood products

International Travel and Commerce

Global travel can rapidly spread disease; illegal exotic bird trade can transfer infectious birds unchecked

Travelers can spread strains between endemic areas; outbreaks in nonendemic areas with appropriate mosquito species (e.g., southern U.S.)

Dissemination of M. tuberculosis on airplanes via recirculation of air

Global travel spreads disease

Breakdown of Public Health Infrastructure

Prolonged nature of the pandemic will strain resources

Lack of effective mosquito control, poor water and sewage systems in developing areas

Inability to monitor tuberculosis population; high treatment interruption rates in developing countries; HIV epidemic areas overwhelmed

Lack of educational and intervention programs, overwhelmed workforce in developing countries

Poverty and Social Inequality

Rapid spread of the virus in the developing world

Developing countries that lack vector control programs risk high incidence

Expense of directly observed therapy inhibits consistent use in poorer nations

Expense of antiretroviral therapy; stigmatization of men who have sex with men, especially in early days of the emergence; marginalized women’s rights in some societies

(continued)

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Table 6.3 (continued)

War and Famine Increased global travel during World War I facilitated propagation of 1918 influenza pandemic

Tuberculosis spreads quickly through refugee camps (e.g., Somalia)

Treatment programs are difficult to administer in areas of conflict

Lack of Will Pharmaceutical industry and vaccine/therapeutic development

Poor surveillance in endemic countries

Inadequate infection control policies or practices

Low research and intervention priority initially for an agent primarily spreading in men who have sex with men; refusal of officials in some developing countries to acknowledge HIV in the population

Intent to Harm Theoretical potential of genetically reconstructed 1918 pandemic influenza virus to be used in an attack

∗ At the time of this writing, pandemic HPAI has not reemerged. Based on knowledge from prior influenza pandemics and extensive studies on influenza virus epidemiology and genetics, experts have uncharacteristically broad insight into factors that affect how these zoonotic pathogens emerge.

a Moncayo AC, Fernandez Z, Ortiz, D, et al. Dengue emergence and adaptation to peridomestic mosquitoes. Emerg Infect Dis. 2004;10(10):1790–1796.

Table 6.4 provides a description of unique features of infectious disease disasters that are not usually encountered in many other disaster response efforts.

The Infectious Agent Infectious disease disasters, unlike other physical and chem-

ical incidents, are caused by biological entities that are diverse and under constant selective pressures to change. So, it may be clear that an outbreak has occurred due to the contagious- ness and nature of the illness that characterize cases present- ing to healthcare facilities; however, the identity of the agent that is making patients sick may be elusive, and any effort to mitigate the disease and spread of the agent will be compro- mised. Cases of severe atypical pneumonia perplexed physicians in Guangdong province, China in 2002. Chinese officials main- tained the causative agent to be a bacterium called Chlamydia.6

It was not until months later, after global spread occurred requir- ing an unprecedented international response effort, that a new coronavirus was publicly identified as the cause of a heretofore- uncharacterized disease, SARS.

For a number of infectious agents, previously known or unknown, there is no specific treatment or cure. Medical man- agement is limited to supportive care, which may require long hospital stays. Depending on the number of afflicted persons, this could affect resource availability (discussed later). The unknown nature of some pathogens also limits detection and diagnostic capabilities.

Infectious agents are often zoonoses. Human infection from the animal reservoir occurs when environmental and behavioral factors coincide to allow for transmission of the agent. In the case of EIDs, the identity of the animal reservoir may be unknown. Successful mitigation of disease spread is contingent on discover- ing the reservoir. The 1993 emergence of hantavirus pulmonary disease in different locations in the U.S. occurred due to increased

contact between rodent and human populations; disease erad- ication followed reduction of human contact with rodent excreta.

The Disease In some situations, the medical literature may not have pre-

viously described the disease (e.g., the various viral hemorrhagic fevers that have emerged over the years), or a particular disease was not previously associated with a type of infectious agent (e.g., acute respiratory disease and hantaviruses). In either case, understanding the mechanism of disease is important to provide effective care and prevent future cases. Incomplete or incorrect disease classification will hamper an effective response effort. Alternatively, a disease may be classically associated with an infectious agent; however, outbreaks are rare and the medical community lacks experience in identifying and treating the dis- ease (e.g., smallpox). This scenario also can affect the timeliness with which a disaster is controlled.

In many instances, an EID has similar symptoms to other diseases that are endemic to a region. SARS patients had gen- eral symptoms of fever, headache, and malaise that typically progressed to pneumonia. Healthcare workers had the daunting task of differentiating patients with respiratory ailments to prop- erly isolate and treat the SARS cases.7 Likewise, a 1995 Neisseria meningitidis outbreak in Minnesota occurred during flu season, overwhelming a hospital emergency department and complicat- ing triage.8

Particularly during epidemics with common symptoms such as headache and fever, healthcare facilities may be inundated with the so-called “worried well.” Although psychology experts have advocated for abandoning this phrase and replacing it with more appropriate terminology such as “medically unexplained symptoms,” it is still often used to refer to persons who think they may have symptoms although they do not actually have the

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Table 6.4: Challenges of Infectious Disease Disasters that May Differentiate Them from Other Types of Disasters

Categorya Challenge

Infectious Agent Novel agent or one not previously associated with disease

No known treatment or cure

Unknown reservoir

May not initially be recognized as the causative agent of the disaster

Disease Not characterized previously

Medical community lacks experience treating

Symptoms are similar to other infectious diseases

People who are concerned about exposure but not truly exposed

Transmission Contagious agent – large numbers infected over time

Global response may be necessary to contain agent

Multiple cities affected

Disaster could last weeks, months, or years

How to decide when the disaster is over

Personnel Exposure of healthcare workers to agent

Healthcare workers absenteeism due to fear of contracting agent

Resources Isolation of cases in the healthcare facility

Decontamination of hospital equipment

Capacity of laboratory to process samples

Distribution of limited supplies (drugs, equipment)

May be other infectious disease outbreaks going on

The Public Quarantine

Screening for symptoms (at hospitals, airports)

Controlling movement (closed borders)

Closing services (schools, churches, public transportation)

Psychological fears

Media relations

Ethics and Law Mass vaccinations

Quarantine/restriction of movement

Allocation of resources

Demands on healthcare workers, first responders

Terrorism Balancing epidemiological and criminal investigations

a The first three categories (agent, disease, transmission) are unique to infectious disease disasters. The remaining categories (personnel, resources, the public, ethics and law, and terrorism) may apply to other types of disasters, but the challenges listed are unique or particularly applicable to infectious diseases disasters.

disease or well persons who may present to healthcare facilities in the hopes of receiving prophylaxis “just in case” (see Chapter 7). These situations are understandable given the fear of contract- ing the infectious disease and the desire to protect oneself and one’s family. Communication with the public is an important component of the response effort to provide information on the disease and actions to take if people think they have been exposed. Ultimately, effective crowd control, screening, and triage may be necessary to separate infected and uninfected persons.

Transmission of the Infectious Agent An infectious disease may be contagious. This occurs when

the transmission rate (R0), the average number of secondary cases to which an infected person spreads the disease when no control measures are used, is greater than 1. Some agents, such as Bacil- lus anthracis (the causative agent of anthrax) are not contagious (R0 < 1) and containment of the disaster is dependent on pre- vention of human contact with B. anthracis spores in the envi- ronment. Many other infectious agents are contagious (R0 > 1). Pandemic influenza R0 estimations vary, but most are approx- imately 2–3.9 This means that one person with influenza will likely infect two other people. Interestingly, in the case of SARS- CoV, the R0 was usually approximately 2–4, yet some people appeared to be superspreaders, passing the virus to at least 10 people.10 This variance in R0 among different hosts complicates predictions of the magnitude of the epidemic.

The implications of a communicable disease agent for disas- ter relief are many. Large numbers of afflicted persons could result from a single “emergence” of an agent or from one bioterrorist attack because more and more people are exposed to the agent. Due to travel of infected persons (e.g., SARS in 2003), or envi- ronmental factors that influence animal ecology (e.g., hantavirus pulmonary syndrome in 1995), the infectious disease may affect many cities, straining the ability of federal and state agencies to assist in local response efforts. Furthermore, as multiple neigh- boring public health jurisdictions are affected, communication and collaboration becomes important. If the infectious agent crosses international borders, a global effort may be required to end the spread of disease. This could include travel restric- tions, surveillance, and the sharing of resources (e.g., vaccines and antibiotics) and technology (e.g., diagnostics).

The communicability of an infectious agent can also affect the duration of the disaster. Rather than resulting in an acute incident, an infectious disease disaster could last weeks, months, or even years as waves of people are affected in a region or across the globe. Pandemic influenza is predicted to last 18–24 months. The AIDS disaster has lasted for decades. Sustaining disaster relief for years will be challenging – resource utilization, a fatigued healthcare workforce, even changing political administrations, can all affect the response and recovery efforts. As mentioned previously, other infectious disease outbreaks will surely occur, requiring an even greater effort from an already overwhelmed system.

Implementation of the incident command system for disaster relief of an acute event such as a fire delineates when the disaster is controlled and afflicted persons are receiving care. When is an infectious disease disaster over? All too often, a period of days occurs when no new cases are diagnosed, the outbreak is determined to be over, and healthcare procedures return to normal; then, the community is hit with a second wave of cases and healthcare facilities must work quickly to reinstate outbreak procedures. The 2003 SARS epidemic curve for Ontario, Canada

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Figure 6.3. Reported SARS cases in Ontario, Canada in 2003 demonstrating the two phases of the epidemic. A) Number of reported cases of SARS by classification and date of illness onset – Ontario, Canada, February 23 – June 7, 2003. B) Number of reported cases of SARS in the second phase of the epidemic by source of infection and date of illness onset – Toronto, Canada, April 15 – June 9, 2003. Adapted from U.S. CDC.∗ See color plates.

demonstrates two phases of increased disease incidence (Figure 6.3A). Provincial public health officials had assumed that the

∗ CDC (U.S. Centers for Disease Control and Prevention. 2003. Update: Severe acute respiratory syndrome – Toronto, Canada. MMWR 52(23):547–550.

outbreak in Ontario was contained at the end of April 2003 because no new cases of SARS were diagnosed after April 20. The World Health Organization (WHO) officials concurred; the travel advisory to Toronto was lifted on April 30 and Toronto was removed from the WHO list of locations with disseminating

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SARS on May 14, 2003. Ontario health officials relaxed the strict hospital infection control directives for SARS. Days later, the second phase of the epidemic in Ontario began. Apparently, patient-to-patient and patient-to-visitor spread of the virus was still occurring unnoticed at one hospital. When SARS control measures were lifted, viral exposure of hospital workers led to a resurgence of cases (Figure 6.3B). Once again, infection con- trol directives were issued, the hospital ceased admitting new patients, and hospital workers faced restrictions and quaran- tine. This example stresses a number of points: 1) Surveillance is critical to limiting the spread of an infectious agent in the healthcare setting. All patients and healthcare workers should be monitored for development of symptoms; 2) Decision makers must be wary of relaxing strict infection control measures too soon. Although officials in Ontario and at WHO waited at least 20 days (two incubation periods) before lifting the SARS direc- tives, this action was complicated by the difficulty in differentiat- ing SARS patients from patients with other respiratory ailments; and 3) The psychological toll on affected citizens, and especially healthcare workers, was immense. This certainly was not the first time an epidemic was prematurely declared resolved, and public health officials were trying earnestly to prevent illness and death. The very nature of infectious agents is often unpredictable, espe- cially when the agent is newly emerging. This reality needs to be balanced with the desire to return an overwhelmed staff and system to normal operations.

Food-borne transmission of the infectious agent injects addi- tional facets to the epidemiological investigation. Identification of the contaminated product(s) can involve: obtaining food his- tories from cases and controls, sometimes weeks after the initial cases surface; extensive laboratory analysis of food and envi- ronmental samples; consideration of food distribution networks and trace-backs to food sources; implications on the food indus- try and consumer perceptions; differences in local, state and national food outbreak surveillance protocols; and ramifications of/to international trade. The 2008 Salmonella serotype Saint Paul outbreak, associated with over 1,400 cases in the U.S. and Canada, was first attributed to tomatoes and then to Mexican hot peppers – and has been the subject of numerous hearings and analyses to elucidate the shortcomings in food safety and outbreak response.11

Response Personnel The communicability of infectious diseases poses a unique

threat to first responders and primary care providers. Although a radiological attack can result in exposure of healthcare work- ers, the mechanism and nature of the injuries is well defined and the threat, once identified, can be relatively easily contained and avoided. In contrast, containing an infectious agent in the healthcare setting can be far more insidious – some people may be asymptomatic carriers of the agent, hospital surfaces may be contaminated, and appropriate personal protective equipment may not be in use. The infectious nature itself of a newly emerg- ing pathogen may not even be recognized. All of these factors can result in exposure of healthcare workers to the agent. SARS in Toronto primarily spread in the healthcare setting (72% of cases were healthcare related), and 44% of cases were healthcare workers.12 In the 1957 influenza pandemic, healthcare workers constituted a large proportion of the infected. The emergence of Ebola-Zaire virus in 1976 devastated the region, including the clinic run by Belgian missionary Sisters. Almost 20 years

later, 30% of physicians and 10% of nurses were infected with Ebola-Zaire during an outbreak in the Democratic Republic of the Congo (formerly known as Zaire).13

It may be necessary to restrict the movement of individuals in a community to prevent spread of the infectious agent. This is particularly true in the healthcare setting where infectious people will congregate and where immunocompromised patients can be exposed. During the SARS pandemic, many healthcare workers were directed to function under work quarantine. These workers were instructed to go to work or stay home, with minimal con- tact outside these areas. Many healthcare workers are stationed at different facilities or have more than one healthcare-related job. The movement of workers between facilities could expose many more patients to the infectious agent, yet prohibiting this movement would leave facilities understaffed.

Health professionals are a dedicated group of individuals who adhere to a code of ethics to provide care for the ill and injured (often referred to as “duty to care”); however, the man- agement of infectious disease outbreaks is stressful. The long hours often due to understaffing, high volume of patients, dura- tion of the outbreak, and publicity can have adverse psychological impacts on responders and primary care providers. If the infec- tious agent is emerging and unknown, highly communicable and/or highly lethal, it is possible that healthcare workers will refuse to perform their duties. In a survey of more than 6,000 healthcare workers, a considerable proportion of respondents said they would be unwilling (or not sure) to report to work dur- ing a smallpox (38%) or SARS (51%) event.14 In contrast, only approximately 15% of respondents said they were not willing (or were not sure) to report to work after explosive or environmental disasters.

The personnel “on call” during an infectious disease disas- ter are not just the direct patient care staff. Public health staff (nurses, epidemiologists, sanitarians, and laboratory technolo- gists) will be involved from the beginning to determine the extent of the disaster, how to stop the spread of the infectious agent (e.g., mass vaccinations), and to identify the infectious agent source (e.g., a rodent reservoir). These efforts necessitate long work hours for days or often weeks. A second unrelated infectious disease outbreak or disaster could occur during or shortly after the first disaster, requiring the same personnel to act without respite. This protracted demand on the workforce may require recruitment of additional personnel not specifically trained for a particular task to maintain the increased level of service (surge capacity). For example, in the 1995 N. meningitidis outbreak in Minnesota, extra people were needed to dispense antibiotics, a job that legally could only be performed by a registered pharma- cist until the licensing board provided emergency authorization. Understanding surge capacity is critical to timely, consistent, and effective remediation of the event.

Resources The availability of resources in public health can be a con-

cern even in the absence of a disaster situation. Recall the long lines, distribution issues, and public attention caused by the 2004 shortage of the seasonal influenza vaccine in the U.S. – the shortage itself became a disaster of sorts. This scenario would be heightened in the event of an influenza pandemic in which disease severity is high and vaccine, if available, will be limited. During an outbreak or epidemic, mobilization of potentially large volumes of preventive and/or prophylactic medicines to the

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affected area(s) is necessary in a short period of time. Approxi- mately 10,000 courses of ciprofloxacin were required to treat the people possibly exposed to anthrax spores in the U.S. in October 2001.15 The 1995 N. meningitidis outbreak in Minnesota resulted in the vaccination of 30,000 people, more than half the popu- lation of the town. The vaccine stock was not available locally and it took 2 days to deliver the medication to the impacted area.

If the infectious agent is contagious, healthcare workers and other response personnel at risk of exposure will be required to use appropriate personal protective equipment (PPE). U.S. hos- pitals use national guidelines for the types of PPE required based on the mode of pathogen transmission (e.g., contact, droplet, or airborne). Details on the types of PPE required for the dif- ferent modes of transmission can be found at the Centers for Disease Control and Prevention (CDC) website (http://www. cdc.gov/ncidod/dhqp/gl isolation.html; Guideline for Isolation Precautions in Hospitals from the Hospital Infection Control Practices Advisory Committee). Extra precautions may be rec- ommended when the agent initially emerges and complete infor- mation on the mode(s) of transmission is not available. For example, evidence suggested that SARS-CoV was not spread by airborne transmission (characterized by dissemination through the air on small particles); however, healthcare workers were often directed to wear airborne PPE (N95 respirators). Consid- eration should be given to ensuring that PPE can be used properly in an emergency situation (e.g., some masks need to be fit tested for optimal functioning) and to contingency plans if not enough PPE will be available.

The healthcare workforce is a resource itself. As workers become ill, stressed, or quarantined, fewer people will be avail- able to care for patients (in fact, the number of patients may increase as workers are admitted as patients). Some of the most qualified people to treat disease will be on the front lines at the beginning of the disaster and at increased risk of contract- ing disease. This may require less experienced individuals from other departments to fill the void. Many healthcare workers died from SARS in 2002 and 2003, including Dr. Carlo Urbani, the WHO infectious diseases specialist in Viet Nam who is credited with discovering the outbreak in that country and taking steps to prevent its spread.

Even with the proper use of PPE by healthcare staff, a conta- gious microbe can spread in the healthcare setting. Examples of such include from patient-to-patient or patient-to-visitor trans- mission. Therefore, the isolation of infectious patients to one area of the facility is recommended. This may necessitate extra equip- ment and supplies dedicated for use in the isolation area. Patients infectious with pathogens spread by airborne transmission (or with emerging pathogens for which airborne transmission is sus- pected) should be sequestered in negative pressure rooms from which air is filtered before recirculation throughout the facility. There are, however, limited numbers of these units and a large infectious disease disaster may require keeping multiple patients in the same room or even the establishment of facilities com- mitted to treating only infectious patients. During other types of large disasters, patients are often transferred to various hospitals in the region. Although this has been successfully accomplished in some infectious disease disasters (e.g., in Singapore during the SARS epidemic), any patient transfer risks further spread- ing of the disease and should be undertaken within the context of overall containment strategies. Furthermore, in systems that allow it, neighboring hospitals may refuse to accept patients from

hospitals with confirmed cases due to fear of the disease spread- ing to their own patients and staff. If the original hospital is designated as an infectious disease facility, these other hospitals may be willing to accept nonexposed patients in transfer thereby increasing capacity for contagious patients within the original facility.

Equipment that is used to treat multiple patients, ranging from stethoscopes to ventilators, must be properly decontam- inated between patients. This may be particularly difficult for new infectious agents for which effective decontamination pro- tocols are not known. Furthermore, taking equipment out of circulation, even temporarily, may delay treatment of patients.

There are usually two general aspects to mitigating an infec- tious disease outbreak: the care of patients (to alleviate disease and suffering) and the epidemiological investigation (to pre- vent further transmission). In both cases, laboratory testing of human and/or environmental samples for evidence of the pathogen is important to ensure the correct intervention strate- gies are directed to the correct people and areas. Although the increase in the number of patient samples during an outbreak is often expected, the number of environmental samples can be quite large. At times, the magnitude of the testing required is overwhelming to even the larger regional, state, national and international laboratories, whose services are required for large incidents and/or for the testing of certain pathogens. For exam- ple, tens of thousands of analytical assays were done on envi- ronmental samples in the 1993 hantavirus pulmonary disease epidemic, in the 1999 West Nile virus emergence in the U.S., and in the 2001 anthrax attacks. The response to an EID outbreak may be largely dependent on the local public health workforce but this response may be directly reliant on the capacity of other health departments and agencies.

Finally, it is important to remember that other infectious diseases, either endemic or disease outbreaks, will be occurring while the infectious disease disaster is occurring. These situations may also require the resources needed for the disaster response.

The Public The 2003 SARS epidemic in Toronto provides numerous

examples of the unique considerations for interacting with the public during an infectious disease disaster. The etiology of SARS was unknown initially, but it was apparent that person-to- person transmission was occurring. Therefore, voluntary quar- antine measures were implemented, representing the first time in 50 years that such measures were used in North America to con- trol disease transmission in a community. Approximately 23,000 people were asked to adhere to home quarantine (remain at home, wear a mask, have limited contact with family mem- bers, and measure their temperatures twice a day) and/or work quarantine. Studies after the epidemic ended suggest that com- plete compliance to home quarantine requirements was low.16

Respondents to a web-based survey indicated confusion over the quarantine instructions and inability to contact public health officials for clarification. Furthermore, the quarantine period was necessarily 10 days, a relatively long time for most people to be away from work and community activities.

For this pandemic, it was not necessary to close borders (within and/or between nations) to general travel. Diseases with higher transmission rates, say smallpox from a bioterrorist attack (estimated R0 = 10),17 may require such stringent measures. Issues to consider are enforcement, the effect on businesses, and the effect on the supply chain for disaster management.

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Table 6.5: U.S. Health and Human Servicesa Select Agents and Toxins

Bacteria Bacillus anthracis (anthrax) Brucella abortus, B. melitensis, B. suis (brucellosis) Burkholderia mallei (glanders) Burkholderia pseudomallei (melioidosis) Clostridium species that produce botulinum neurotoxins Coxiella burnetii (Q fever) Francisella tularensis (tularemia) Rickettsia prowazekii (typhus fever) Rickettsia rickettsii (Rocky Mountain spotted fever) Yersinia pestis (plague)

Viruses Cercopithecine herpesvirus 1 (Herpes B virus) Crimean-Congo hemorrhagic fever virus Eastern equine encephalitis virus Ebola virus (viral hemorrhagic fever) Hendra virus Lassa fever virus (viral hemorrhagic fever) Marburg virus (viral hemorrhagic fever) Monkeypox virus Nipah virus Reconstructed 1918 influenza virus Rift Valley fever virus South American hemorrhagic fever viruses Tick-borne encephalitis complex (flavi) viruses Variola major virus (smallpox) and Variola minor virus (alastrim) Venezuelan equine encephalitis virus

Fungi Coccidioides immitis (coccidioidomycosis) Coccidioides posadasii (coccidioidomycosis)

Toxins Abrin Botulinum neurotoxins Clostridium perfringens toxin Conotoxins Diacetoxyscirpenol Ricin Saxitoxin Shiga-like ribosome–inactivating proteins Shigatoxin Staphylococcal enterotoxins T-2 toxin Tetrodotoxin

a All agents are on the U.S. Health and Human Services list. Some agents overlap with the USDA list, which is not completely represented here.

Source: CDC (http://www.cdc.gov/od/sap/docs/salist.pdf).

Institutions within a community where people congregate may require closure, including schools and places of worship.

Whether or not movement or quarantine measures are implemented, public fear and psychological trauma will likely be high for both contagious and noncontagious diseases. This fear will be a function of exposure risk to the agent and sub- sequent infection, the severity of illness, and the availability of treatment for themselves and their dependents. Media coverage during the disaster can do much either to allay or stoke pub- lic fear, depending on perceptions of the mitigation effort and accuracy of the messages.

Ethics and Law There are many ethical and legal considerations in an infec-

tious disease disaster response. The following issues are given as examples.18

■ The process of making population-based decisions for infec- tion control during a disaster (e.g., mass vaccinations, quar- antine, and movement restrictions) will raise concerns about the legality and necessity of individual rights infringements.

■ A scarcity of resources such as vaccines, therapeutics, or hos- pital equipment will require difficult decisions about who receives the resources and who does not.

■ In the event of a disaster caused by, for example, a highly con- tagious, highly virulent, uncharacterized, and/or genetically engineered agent, to what extent should first responders and healthcare workers be expected to comply with duty to care orders for the public good?

Terrorism This chapter will not elaborate on preparedness specifi-

cally for bioterrorism events because disease, as well as trans- mission management, will essentially present itself similarly to other microbial threats. Bioterrorism is addressed in Chapter 29. The criteria to be considered will include most of those already described, albeit some will be particularly relevant (e.g., public fear, the number of affected areas, and laboratory capacity). The U.S. Department of Health and Human Services (HHS), specif- ically the CDC, maintains a list of select agents and toxins that are likely candidates for use as bioweapons against human beings (Table 6.5). Many of the agents on this list, including the anthrax spores released in the U.S. postal system in 2001, smallpox, and the hemorrhagic fever viruses, are not commonly seen by the medical community in the Western hemisphere. A bioterrorist may use an agent that has been genetically engineered to be highly virulent, resistant to therapeutics, and/or to cause a novel disease. In these cases, health professionals will be at a further disadvantage to prevent disease and death.

As with every terrorist attack, a criminal investigation should ensue after a bioweapon is used. In other types of attacks, this investigation begins immediately after the actual incident has occurred (e.g., an explosion) during the aftermath and rescue efforts. When a bioweapon is used, it may be days or longer before exposed people develop symptoms. Depending on the agent used, it may be an even longer time before a crime is suspected. The site or mechanism of the actual agent release may never be known. If the agent used in the attack occurs naturally in the region, foul play may not even be suspected. Table 6.6 lists some clues that suggest an outbreak could be due to criminal activity. Although the criminal investigation will focus on finding the perpetrators of the attack, a second investigation – an epidemiological investigation – will be progressing as well to determine the cause and spread of disease. Both investigations will require sample analysis and interviews with the public and must progress without hindering each other.

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Table 6.6: Indications that an Infectious Disease Outbreak in the U.S. May Be due to a Bioterrorist Attack

Category Indication of Bioterror Attack a

Agent The disease or agent is not usually seen in the region (e.g., smallpox anywhere in the world; plague caused by Yersinia pestis on the East Coast of the U.S.).

Multiple geographically distant areas have disease outbreaks occurring at the same time due to a genetically identical strain of an agent. (e.g., identical Francisella tularensis strain causes outbreaks in Washington, DC, St. Louis, MO, and Las Vegas, NV) Note: unintentional food-borne outbreaks may display this incidence pattern if the contaminated product is widely distributed.

Genetically engineered to be resistant to multiple antibiotics, particularly those commonly used to treat disease (e.g., ciprofloxacin-resistant B. anthracis).

Genetically engineered to cause a novel disease for that agent (e.g., incorporation of genes that cause symptoms of a chronic disease).

Genetically engineered to be more virulent than usual (e.g., incorporation of genes for toxin production; reconstructed 1918 influenza virus).

Host/Environment Larger number of casualties in a region in a short period of time compared to expected incidence.

Cases do not have risk factors for exposure (e.g., brucellosis cases without known exposure to contaminated foods or infected animals). This may indicate an unconventional infection route, such as aerosolization of the Brucella pathogen.

Cases may have risk factors for exposure, but no common exposures (e.g., all salmonellosis cases ate from restaurant salad bars, but they ate different foods at different restaurants).

Environment Case distribution and/or environmental distribution of the agent follow wind trajectories (e.g., accidental release of anthrax spores in Sverdlovsk, USSR in 1979).

Other types of attacks (e.g., chemical, radiological) occur at the same time.

More than one outbreak (with potentially larger numbers than usual) in a region caused by different agents, especially if one or more agents is uncommon.

An outbreak of disease in an unexpected season, or that does not follow usual global incidence trends (e.g., SARS in August in the U.S. without cases in other countries).

a More than one indication may be present after an attack.

The amount of microbiological sampling after an act of bioterrorism will likely be extensive. Contaminated areas could have very high concentrations of the bioweapon, risking cross- contamination of personal protective equipment and transfer of the agent to other surfaces in the area or other regions. The crim- inal investigators must take precautions to avoid contracting dis- ease. In the 2001 U.S. anthrax attacks, investigators had to develop microbiological methods specifically for dried spores. Still, han- dling the most contaminated samples, including both the attack letters and cross-contaminated letters, created aerosolized spores and a very hazardous situation.19

STATE OF THE ART

As with other types of events, the response to an infectious dis- ease incident of any origin is only as effective as the monitoring and relief infrastructure in place. After the 2001 anthrax attacks, the U.S. entered a period of heightened awareness of infectious disease threats. An era of preparedness ensued, with the U.S. Congress allocating unprecedented sums of money to enhance the response to bioterrorism. The immediacy for response action plans was amplified by the 2003 emergence of SARS∗ and the

∗ LeDuc JW, Barry MA. SARS, the first pandemic of the 21st century. Emerg Infect Dis. 2004 Nov. Available at http://www.cdc.gov/ncidod/EID/ vol10no11/04-0797 02.htm. Accessed January 13, 2009.

threat of pandemic influenza. These events have highlighted the possibility of a large infectious disease disaster and broadened the scope of many preparedness plans.

Preparedness is the state of being ready to act. In the infec- tious disease disaster context, it broadly refers to the ability to detect a pathogen, act to prevent its spread, and mitigate dis- ease in humans (or animals or plants). Accomplishing this is no small task, given the large number and variability of pathogenic microbes, the potentially rapid global spread of disease, and the extent of communication required between individuals, agencies, governments, and nations. Furthermore, the working definition of “infectious diseases disaster preparedness” and the mecha- nisms and priorities to achieve it can vary widely between juris- dictions and nations. Because the exact nature of the infectious disease in a disaster situation cannot be known in advance, cur- rent planning procedures are largely dependent on assessment and subsequent remediation of response vulnerabilities (often identified from previous events and practice exercises).

Figure 6.4 shows a general schematic of selected response stakeholders and the activities that occur before, during, and after a biological incident. While not all inclusive, the diagram serves to illustrate 1) the ongoing nature of EID preparedness, surveillance and response, 2) the complexity of the response, 3) the overlapping responsibilities of stakeholders, and 4) the cur- rent “feedback” approach to EID preparedness. The light grey circle just outside the heavy black line (designated “Biological Incident Occurs”) diagrams the “incident threshold.” This circle

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Figure 6.4. Schematic of events before and after a biological incident. “Incident” refers to the exposure of a population to a newly emerging disease (e.g., SARS), to an infectious disease with the potential for extensive casualties and/or public fear (e.g., Neisseria meningitidis), or to an act of bioterrorism. Represented are examples of the factors that need to be considered before, during, and after an incident. Increased size of the concentric circles generally corresponds with the progression of time; however, events in larger circles may “feed back” on smaller circles. The use of circles symbolizes the interconnectedness of entities and events within each ring.

The center of the diagram (“Preincident State”) represents the situation prior to a biological incident; during this phase, the various response stakeholders (e.g., Public Health, Healthcare, First Responders/Law Enforcement and Communications) enhance preparedness by, for example, improving response plans and participating in practice exercises. This aims to fortify comprehensive preparedness plans (second ring labeled “Preparedness”) and surveillance activities (third ring labeled “Surveillance”). The heavy black line represents the occurrence of an actual biological incident. After this happens, a period of time ensues when response stakeholders should become aware of the incident (fourth ring labeled “Incident Threshold”), either by active detection through surveillance efforts or passively by presentation of cases to healthcare personnel. Depending on the agent, the incident may not be initially apparent. This time between the occurrence and detection of an incident is the “incident threshold.” Response plans are activated (fifth ring labeled “Response Plans Activated”) when the incident is recognized. Some elements of the response are shown to illustrate the types of actions the preparedness stakeholders may need to take. This includes agent identification and development of diagnostics/vaccines/therapeutics, activities that will not be timely for an EID unless solid scientific programs are in place in the Pre-incident State. The events in the final circle (sixth ring labeled “Post-Incident”) largely occur in the post-incident phase when disease transmission has been controlled and no new cases are detected. Some actions such as the clean up of environmental contamination may initiate sooner to prevent disease transmission. Disaster mitigation efforts are analyzed in the post-incident phase. “Knowledge Gained” is used to optimize preparedness plans for the next potential biological incident (this flow of information is symbolized in the inset). Effective planning and surveillance in the circles before an incident occurs can reduce the incident threshold time and make the events of the subsequent circles easier to manage. See color plates.

represents the time it takes for detection of the biological incident (during which time agent transmission progresses essentially unchecked), and can determine the extent of response measures necessary. This section of the chapter discusses the components of infectious disease preparedness that aim to facilitate response activities and minimize the duration, disruptiveness, and impact of the incident. The text uses the U.S. perspective to illus- trate one approach to EID preparedness. Other countries may

address these issues differently. Nonetheless, the section high- lights some of the considerations for infectious disease disaster preparedness.

Disaster Response Plans

As the aftermath of hurricane Katrina in the U.S. has demon- strated, a large event can overwhelm a response system. The

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predicted characteristics of infectious disease disasters outlined in the previous section, coupled with evidence from past inci- dents, serve as tools for understanding the challenges of the next EID disaster. Questions such as “who is in charge?” and “how well do different jurisdictions interact?” have been the subject of many workshops, symposia, and planning meetings that have occurred at local, regional, national, and international levels.

Local, State, and National Systems The response effort to an infectious disease outbreak usu-

ally begins with local authorities as the first cases of disease are reported. Therefore, local preparedness plans can do much to prevent dissemination of the infectious agents to other regions. This is particularly important in the event of a bioterrorist attack when more than one locality may be affected at the same time, straining national and international assistance mech- anisms. In response to the terrorist events of 2001, the U.S. government appropriated over a billion dollars to the states to augment disaster preparedness. The CDC Public Health Emer- gency Response Guide suggests that each local jurisdiction and state should have a general incident response plan in place that establishes the following: working relationships between local public health partners (e.g., health departments, emergency management agencies and services, fire and law enforcement, hospitals and their emergency departments, volunteer/aid orga- nizations, emergency planning committees and response coor- dinators, academic institutions, private businesses, and neigh- boring health jurisdictions), risk and hazard assessments for the area, a risk communication plan, resource and surge capac- ity, operational objectives, procedures and guidelines for action during a disaster that are in line with the Department of Home- land Security (DHS) National Response Framework (NRF) and the National Incident Management System (NIMS), surveil- lance systems to monitor public health, a trained public health workforce (e.g., on proper use of personal protective equip- ment, emergency operations procedures, incident command sys- tem), and exercises to evaluate and review response plans. Spe- cific plans for biological incidents should address operations in the event that the agent spreads to or from neighboring jurisdictions.

At the time of this writing, within the U.S. system, Federal aid for Incidents of National Significance is meant to supplement the local and state response and is considered for distribution upon request by the state using the NRF. The NRF is structured in the framework of the NIMS, a unified command approach to disaster response that directs different organizational branches as required. Federal funding to support state, local, and tribal preparedness plans is dependent on NIMS compliance. The “all- hazard” approach of the NRF necessarily gives broad guidelines for the organization of the response so that procedures apply to many situations. The NRF also outlines more specific consider- ations for certain types of incidents; for example, depending on the nature of the incident, certain Emergency Support Functions can be implemented. The Biologic Incident Annex “describes incident management activities related to a biological terrorism event, pandemic, emerging infectious disease, or novel pathogen outbreak.”20 This Annex, coordinated by HHS, evokes primar- ily the Public Health and Medical Services Emergency Support Functions. This entity defines the core functions for supplemen- tal federal aid to be the assessment of public health and medical needs, public health surveillance, medical care personnel, and

medical equipment and supplies. The Biologic Incident Annex also delineates special considerations (e.g., surreptitious nature of a bioterrorist attack, the importance of surveillance systems), policies (e.g., collaboration with the Environmental Protection Agency in the case of environmental contamination, involvement of the Federal Bureau of Investigation [FBI] during a bioterrorist attack), concepts of operations (e.g., effective response elements such as detection and containment), and planning assumptions (e.g., multiple jurisdictions may be affected, disease transmis- sion mode is important) that are unique and/or fundamental to a biological incident response.

An important distinction between typical infectious disease disasters and many other disasters is the lack of a specific and immediately recognized incident initiation point (rather, there is an “incident threshold” period). With the notable exception of the anthrax letter terrorist attacks in the Fall of 2001 (which behaved more like discrete chemical incidents), by the time a biological agent is detected in the U.S., many people in diverse areas may be affected. The response plan initiates well after media involvement, public awareness, and possible maladaptive behav- ior have occurred. Biological incidents also have the potential to spread to the international community. In this case, the U.S. Department of State becomes involved in conjunction with HHS to alert international health agencies such as the WHO of the outbreak. This action should occur early in the disaster response effort to help prevent global spread of disease.

Within the U.S., many local jurisdictions have improved neglected infectious disease surveillance and response networks since receiving the federally allocated funds. There is a tendency to formulate broad goals and intentions for preparedness how- ever; distinct plans at the local level are often not formed due to lack of information, lack of consensus, and/or lack of priority standing. Practice exercises still uncover lapses in communica- tion and resource allocation. Furthermore, the specifics on when to enact the NRF for federal aid have proven to be confusing. Hurricane Katrina in 2005 occurred shortly after the NRF was established (then known as the National Response Plan), but controversy on when to “federalize” the response was rampant and public. Criticisms of the response have focused on inade- quate communications, including the failure of federal officials to declare the hurricane a “Catastrophic Incident” that super- sedes a state request.21 In any case, data from the Hurricane Katrina response can be analyzed to better enact the NRF in the event of a biological incident. For example, the U.S. CDC is using the Hurricane Katrina response to plan better for the response to pandemic influenza (CDC website).

Hospital Emergency Management Systems Hospitals should be aware of the unique aspects of large

infectious disease outbreaks that could compromise the usual functioning of a disaster management system. These include the transmissibility of the infectious agent to persons not involved in the initial outbreak, the protracted nature of the incident as the agent spreads through the community, and the possibility of infection and absenteeism in hospital staff. Contagious agents necessarily confer an environment of population-based decisions to prevent widespread transmission to the community, which differs from the individual-based care customary of critical care and emergency medicine.

Hospitals should be prepared to operate using an Incident Command System (ICS) during an infectious disease disaster situation. Functioning within an ICS has the advantages of a

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pre-event determined assignment of roles, ease of coordination of multiple facility responses, and scalability of the response as the disaster progresses or is resolved. Within the U.S., facilities that receive medical and trauma patients on a daily basis are required to be NIMS compliant, which allows for the coor- dination of response efforts on a national level. Compliance includes the implementation of a number of elements in the areas of command and management systems, preparedness plan- ning, workforce training, preparedness exercises, resource man- agement, and communication and information management.22

Within these areas, hospitals and healthcare facilities must plan for possible bioterrorism or large-scale infectious disease events. For these types of disasters, infectious disease specialists and infection control experts should be included in the incident command organizational chart to provide guidance on the management of potentially infectious patients with respect to triage, care, further assessment, and the handling of infectious decedents.23

An important component of the hospital response to a com- municable disease is infection control policies to prevent the spread of the agent to healthcare workers. Hospital ICS plans for communicable disease disasters must assume that a proportion of the people in the command structure will be unavailable for duty due to illness or the need to care for ill family members. Pre- paredness includes a mechanism for real-time alternative assign- ments for each role in the command structure. Hospital infection control may also result in the temporary discontinuation of elec- tive procedures. With adequate prior training, personnel from these areas can be diverted to critical response areas that are overwhelmed.

In an infectious disease disaster situation, potentially exposed persons will present to many hospitals in a region. A coordinated incident command Emergency Operations Center for all hospi- tals in a region is a particularly relevant system given the issue of resource availability; however, cooperation between facilities may be limited. Hospitals not yet affected by the disaster must balance the responsibility to assist in the emergency and accept patients with the need to prevent spread of a contagious agent. Transfer of resources such as ventilators and prophylactic medi- cations to overwhelmed facilities may also be hindered because hospitals not yet involved anticipate future casualties. Therefore, hospital preparedness plans for mass casualty bioevents should also include response actions in the situation of limited outside assistance. Additional recommendations have been published on infection control, the types of interventions to use, decid- ing who should be treated, and who should administer care.24

These recommendations, although developed for an intentional attack, can guide planning for all types of infectious disease disasters.

Admittedly, the need for extensive infectious disease disaster management plans has been publicly debated. Arguments have been made that the threat of an infectious disease disaster with a high human toll, such as pandemic influenza, is greatly exag- gerated. Modern day medicines and technologies have provided an arsenal against microbes not available during historical epi- demics. Yet this is hard to gauge for novel pathogens, including new pandemic influenza strains. Nonetheless, some assert that the constant barrage of reports on the lack of preparedness only serves to either reduce public confidence in the event that any infectious disease outbreak occurs or fosters an atmosphere of complacency.25 SARS is often used as an example: public concern and economic loss were extensive, but there were only approxi-

mately 8,000 cases and 750 deaths worldwide. It would seem that the world overreacted. Recall, however, that the causative agent, transmission rate, treatment, and mortality of this new respi- ratory infection were not known at the beginning of the pan- demic. During this time of uncertainty, global spread occurred only weeks after international awareness of a new disease. Fortu- itously, the SARS-CoV was not as infectious as initially thought. This pandemic serves as a warning that preparedness plans are necessary, especially in the event of an EID with high trans- missibility.

Mechanisms to Prevent Disease Transmission in the Community

Specific actions taken by responders during an infectious dis- ease disaster will depend on the nature of the agent. In general, the transmission rate will determine the extent of the measures necessary for containment. Of course, this may not be known at the beginning of an EID outbreak and will have to be predicted from epidemiological data on the initial cases. In the event that the agent is transmissible from person to person, mechanisms of varying degrees of restriction can be implemented. The concepts of isolation, quarantine, evacuation, shelter-in-place, and social distancing are important containment strategies. Whether these measures are implemented in a voluntary or mandatory fashion will depend on the agent and on legal and ethical considerations. Control of a contagious disease may also require contact tracing, which involves identifying and locating the people with whom an infectious person has come in contact, and the mass distri- bution of prophylactic medication or vaccination if available. Implementing controls at national borders to prevent inbound travelers from importing the infectious agent are an option but may be very difficult in some countries and may not be highly effective. Models of pandemic influenza in the U.S., for exam- ple, suggest that even if incoming infections were reduced by as much as 99%, this would only delay peak disease incidence by approximately 3 weeks.

Some infectious disease outbreaks may require rodent or arthropod control programs to eliminate reservoirs or vectors that carry the agent. This can be challenging for EIDs of unknown (or mistaken) etiology. An outbreak of suspected St. Louis virus encephalitis in New York in 1999 prompted mosquito control and public education activities. Experts soon realized that the encephalitis cases were actually caused by West Nile virus, a closely related virus that is transmitted by a broader range of mosquitoes. The initial intervention strategies were expansive enough to be constructive but were optimized with the new diagnosis to the different habitat and activity patterns of West Nile virus–carrying mosquitoes.26

Control of zoonotic diseases may require extensive elimina- tion of animals of agricultural importance. The emergence of Nipah virus in Malaysia and avian influenza in Asia in the early 2000’s resulted in the slaughter of millions of pigs and fowl, respectively.27,28 Although arguably necessary to prevent disease transmission to humans, this type of activity can have many negative consequences. Economically, segments of the agricul- tural industry may be devastated due to decreased production, costs of disease containment and clean-up, trade embargoes, and reduced consumer confidence. Associated industries such as transportation, suppliers, and food service would be affected. Public reaction to an extensive or prolonged slaughter may put political pressure on decision makers to develop other methods for disease control.

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Science and Technology

Scientific advances in molecular biology over the last half cen- tury, and particularly in the last 20 years, have greatly benefited infectious disease public health. The successes of the core goals of public health in any infectious disease disaster, namely detection of an outbreak, prevention of its transmission, and mitigation of disease, are all functions of the body of scientific knowledge on the pathogen and the technological capabilities to translate that knowledge into action. In the case of an EID, this specific kind of knowledge may initially be sparse. This highlights the need for solid work in basic infectious disease biology, because EIDs will likely (but not always) be novel strains or species of known infectious agents.

Basic scientific research on the bioterrorism potential of select agents has increased dramatically in the last few years, pro- viding insight into their pathogenic mechanisms. These advances can lead to the discovery of targets for novel countermeasures and/or to new diagnostic tools. Some critics have suggested that extensive funding for specific select agents is detrimental to pre- paredness goals. Biodefense research needs to be translatable to infectious diseases in general, and to public health policy.

Identification and Characterization of the Agent Standardized techniques, such as microscopy and cultiva-

tion, are very useful in determining the nature of the agent (e.g., the type of bacteria) and whether any known therapeutics are active against it. Further genetic and molecular analyses, includ- ing polymerase chain reaction and immunofluorescence tech- niques, can differentiate the agent from other similar microor- ganisms. Along with these types of assays, genome sequencing (the identification of the nucleic acid composition of the organ- ism’s entire DNA) can determine if the etiological agent is a previously identified pathogen or if it is a novel pathogen and newly emerged. For example, the SARS coronavirus was only distantly related to other known human coronaviruses (an etio- logical agent of the common cold) and produced a very different disease, so it is considered to be a newly emerged variety of this type of virus.29

Obstacles to rapid and definitive identification and character- ization of a novel agent are many. Known animal models may not exist, precluding the ability to show that the isolated agent does indeed cause disease. Culturing techniques to grow microbes in the laboratory are very specific for different types of agents, even within the same genus. Due to the unknown nature of trans- mission and disease severity, specialized containment labs with specifically trained staff may be required. Many regional testing laboratories do not have the equipment or experience to conduct molecular testing.

Diagnostic Assays Diagnostic assays are important to quickly identify new cases

of disease, to differentiate between cases and noncases with sim- ilar symptoms, and to determine environmental sources of the pathogen. Genetic tests are often developed due to the rapid- ity and relatively high analytic sensitivity (ability to detect small amounts of the agent) and analytic specificity (ability to dif- ferentiate the agent from other organisms) of the results com- pared with conventional laboratory techniques. Time is often required to create these assays. During an EID situation, sig- nificant pressure exists for rapid development of diagnostics so that clinicians and epidemiologists have a tool to identify

new cases. These first-line diagnostics are useful, but they may have a higher risk of producing false-negative and false-positive results.

Therapeutics Antimicrobial drug discovery waned in the 1960s when phar-

maceutical companies turned their attention from the suppos- edly declining threat of infectious diseases to the more pressing and lucrative concerns of chronic illnesses. Now, in the face of increasing antimicrobial resistance and emerging agents, new therapies are needed. Scientists are using molecular and struc- tural biology techniques to understand microbial pathogenesis. This information can enhance approaches to discovering novel classes of drugs that block pathogenic processes. The drive for the discovery of new drugs effective against bacteria and viruses has not been an industry priority, however. From 1998 to 2003, only nine new antibacterial drugs were approved, the same number as those approved for just one virus alone, HIV, in the same period. More important, only two of the nine antibacterial drugs had novel mechanisms of action.30

Emerging agents provide a unique challenge for therapeutic design. As noted previously, treatment options for EIDs may be limited, with even broad-spectrum antimicrobial drugs having little or no effect. Information is learned about the causative agent and the disease as the outbreak or epidemic progresses but using conventional therapies (such as specific immunomodulat- ing factors) that work for similar diseases is risky without effi- cacy studies. In a systematic review of more than 50 published studies that assessed treatment efficacy during the 2003 SARS pandemic, no therapy (including antivirals, corticosteroids, intravenous immunoglobulin, convalescent sera, and type I interferon) conclusively improved patient outcomes. In fact, some studies reported possible harmful effects of treatment with ribavirin or corticosteroids.31 The development of novel drugs for an EID is challenging. Even if a molecular target is discovered, the design, development, and approval of a therapeutic agent would not be rapid. For example, in the U.S. it takes approxi- mately 8 years for a new drug to complete clinical trial phases, gain approval, and be marketed. Furthermore, factoring in the relatively low numbers of cases of an EID initially, the chance that the epidemic will end with no further cases, and the high cost of drug development, pharmaceutical companies would be unlikely to even initiate the discovery process without govern- ment intervention and/or incentives.

Vaccines Vaccines are one of the most successful public health tools

to improve the health of populations. By preventing infectious diseases, vaccines limit human suffering and the spread of conta- gious agents. There are many infectious diseases that are endemic in parts of the world for which no vaccines are available. Find- ing mechanisms to produce effective vaccines is the subject of extensive basic research. Molecular and genetic advances have vastly improved the understanding of immune system regula- tion and of vaccine delivery methods. Translating this knowledge into approved vaccine products has been slow for numerous reasons. In some cases, the knowledge base on the infectious agent simply is not advanced enough to make a vaccine. For example, some viruses have high mutation rates; consistent vac- cine efficacy is difficult because mutated forms of the viruses arise that are not affected by vaccine-enhanced immune functions. As with therapeutic development, pharmaceutical companies are

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hesitant to engage in vaccine design. The return on investment is relatively low, demand for vaccines that target sporadically occurring agents is unpredictable, some vaccines for endemic diseases are not extensively used (e.g., yellow fever in Africa and South America) and safety and liability issues abound.

Government Incentives After the terrorist attacks of 2001, the U.S. federal govern-

ment implemented Project BioShield to “accelerate the research, development, purchase, and availability of effective medical countermeasures against biological, chemical, radiological, and nuclear agents” (HHS website). The three main goals of Project BioShield are to 1) provide funding for the procurement of crit- ical medical countermeasures, 2) give authority to the National Institutes of Health of HHS to prioritize the granting procedure for research and development of medical countermeasures, and 3) assist in the use of medical countermeasures during an emer- gency. BioShield lays the groundwork for increased vaccine and drug development for bioterrorist agents. Major pharmaceutical companies have not utilized this funding system due primarily to concerns about liability protection for expedited countermea- sures that cause human harm. Funding smaller biotechnology companies can help fuel an industry, but the risks for both par- ties involved are greater. Some companies may not be able to produce the contracted pharmaceutical after receiving federal funding or the government may opt to purchase less of the prod- uct than expected.

The U.S. pharmaceutical industry needs motivation beyond Project BioShield to expand antimicrobial therapeutic and vac- cine development. In this regard, the Pandemic and All-Hazards Preparedness Act was approved in December 2006. This Act directs the formulation of the Biomedical Advanced Research and Development Authority (BARDA) within the Department of Health and Human Services. BARDA is charged with promoting the translation of scientific research into antimicrobial products, including provisions to induce participation by the pharmaceuti- cal industry. The creation of BARDA is not without controversy. Consumer advocacy groups question the safety of using expe- dited drugs even in emergency situations. Scientific associations are concerned about the lack of transparency of BARDA activities and decisions, the potential for gaps in or duplication of research efforts, and funding sources and amounts.32

Dual-use Risk The 2001 anthrax attacks in the U.S. made the fear of a

bioterrorist attack a reality. To increase preparedness against future attacks, the American government has allocated billions of dollars for biodefense research and development on cer- tain pathogens (Table 6.5). Policymakers realized, however, that increased research on select agents could increase the risk that the agents, or scientific information learned about them, would fall into the hands of terrorists. As a result, measures have been taken through the Biopreparedness Act to limit access to the select agents, regulate genetic manipulations of these agents, and restrict publication of information that could lead to enhanced virulence of the select agents. The Biopreparedness Act also mandates FBI clearance rules for scientists working with select agents. The National Science Advisory Board for Biosecurity was formed to oversee the balance between increasing scientific research to prepare better for a bioterrorist attack and prevent- ing potential adversaries from accessing scientific reagents and information.

Surveillance

Surveillance systems function in an ongoing capacity to “collect and monitor data for disease trends and/or outbreaks so that public health personnel can protect the nation’s health” (CDC website). There are four basic components to surveillance: mon- itoring for disease, detection of disease, analysis of data, and dis- semination of findings. The sooner the detection of an infectious disease outbreak or emergence occurs, the faster the response can be to prevent spread of the agent and human disease. In addition, early detection can prevent the dissemination of the pathogen to other regions or countries and potentially prevent an epidemic or pandemic situation.

Surveillance is also an assessment tool for the general func- tioning of a public health system. Monitoring disease incidence, morbidity, and mortality can indicate regions that must boost existing public health infrastructure. These regions would be more likely to suffer greater casualties during an infectious dis- ease disaster.

National Surveillance Efforts Healthcare practitioners play a central role in the surveil-

lance process by notifying public health authorities regarding patients with reportable diseases or atypical symptomatology. For example, U.S. physicians in the early 1980s noticed that young men were contracting Pneumocystis carinii pneumonia and/or certain malignancies not normally associated with that demographic group. This was one of the first indications that a new immunocompromising infectious disease (now known as AIDS) was circulating in the population.

This classic method of outbreak identification is a key com- ponent of disease control in a population, but relying on it solely is problematic. Recognition of cases that should be reported and subsequent data submission are not always timely. There is heavy reliance on subjective determination of what should be communicated to public health and not all infectious dis- eases are reportable. Furthermore, early surveillance opportu- nities that could potentially prevent human disease and death may be missed. In the first North American outbreak of West Nile virus in 1999, unexplained bird deaths had been noticed 2 months prior to the human outbreak investigation, but no extrapolation was made to possible human consequences.

Recognizing the value of time, many health departments, health agencies and governments have developed a number of surveillance systems and networks to more rapidly and consis- tently detect disease events. Examples of the types of systems include 1) those that monitor the environment for the pres- ence of bioterrorism agents (e.g., BioWatch in the U.S.), 2) those that collect data from different regions to monitor and provide assistance for infectious disease cases (e.g., the U.S. CDC’s Early Warning Infectious Disease Surveillance program for northern and southern border states), and 3) syndromic surveillance. Typical syndromic surveillance systems analyze health data prior to disease diagnosis, such as diagnostic coding or over-the- counter drug sales, to give early indication of a possible infec- tious disease outbreak (e.g., BioSense, ESSENCE). Major chal- lenges to effective national surveillance systems are interagency operations, data integration, and validity testing. These types of problems can be overcome if prioritized, as exemplified by the highly developed U.S. national response network for food- borne outbreak surveillance (FoodNet) and agent characteriza- tion (PulseNet).

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International Surveillance Efforts Globalization has conversely made international infectious

disease surveillance both increasingly necessary and possible. Emerging infectious agents can arise in any country and poten- tially spread globally due to travel and commerce. Clearly, quick identification of when an outbreak emerges will give public health officials, clinicians, and researchers throughout the world an opportunity to prevent dissemination and to develop diagnos- tics and therapeutics. Increased global interactions, which can promote spread of a disease agent, can also encourage coopera- tion in surveillance efforts.

Disparities exist in the capabilities of different countries with respect to workforce, tools, and effort. Many developing coun- tries have a strained public health infrastructure that cannot extend to support intensive surveillance efforts. Therefore, global partnerships that link networks from many regions and coun- tries, such as those supported by the WHO Member States, can serve to share expertise and information.

Reporting compliance is a necessary component of global surveillance. Some countries may delay reporting a disease out- break to avoid stigmatization and negative impacts on travel and trade. Others may believe that an outbreak is under con- trol and of little threat for further spread. Although cases of SARS first appeared in Guangdong Province in November 2002, Chinese officials only confirmed the outbreak to the WHO in February 2003 after international surveillance networks were alerted through media and Internet reports.33 Chinese public health officials worked with the WHO to control the out- break, but international dissemination had already occurred. In response to the SARS pandemic, the Chinese government has overhauled its infectious disease surveillance and reporting systems. Of course, the public health infrastructure problems that delayed the Chinese response are not unique to that coun- try, substantiating the need for international collaborations to detect EIDs and support mitigation efforts. In May 2005, the World Health Assembly adopted the International Health Reg- ulations (2005)∗ – international law that provides a framework for enhancing the surveillance, assessment, notification, and con- trol of public health emergencies of international concern, while limiting unnecessary interruption of global traffic and trade. In general, State Parties to the IHR (2005) became bound by the agreement on June 15, 2007.

Workforce Preparedness

Workforce preparedness is the state of readiness of public health, public safety, and healthcare employees to act in an infectious disease emergency. Workforce readiness is primarily related to workforce capacity and education/training. The concept is often used to describe readiness at the community and state level, but EID or large biological incidents will likely require participa- tion on a national level as well. The jobs performed by these employees are critical to the proper and sustainable functioning of the other preparedness requirements such as surveillance and resource management. Furthermore, practice exercises and past disasters have demonstrated that the response and mitigation effort is improved by good working relationships between public health, public safety, and healthcare workers.

∗ World Health Organization Website. Available at: http://www.who.int/csr/ ihr/en/. Accessed January 12, 2009.

Public Health Workforce Inadequate public health workforce numbers and expertise

are not limited to developing nations. For example, it is well established that decades of budget cuts and neglect have resulted in an understaffed public health infrastructure in the U.S. This has compromised the ability to respond effectively during an infectious disease disaster. In some jurisdictions and facilities, especially smaller ones, the roles of public health nurses, labora- tory technologists, epidemiologists, and infection control prac- titioners are accomplished by staff with multiple duties. Fur- thermore, these positions are often characterized by staff who are reassigned when needed, by employees working overtime, and/or by the use of temporary workers. These options will be limited during an infectious disease disaster as demand for these employees will increase and movement between facilities will be restricted.

Formal education of public health workers in the U.S. for epi- demic situations largely rests on the CDC. The Epidemic Intel- ligence Service (EIS) is probably the most well-known program. For more than 50 years, the EIS has trained public health profes- sionals with hands-on field experiences in epidemiology. CDC Public Health Leadership Institutes, provided in partnership with academic institutions, groom public health workers for leader- ship positions at the state and local level and promote networking between jurisdictions. In 2000, the Association of Schools of Pub- lic Health and the CDC established a network of 38 Centers for Public Health Preparedness in academic institutions to train the public health workforce in such fields as disaster epidemiology, emerging biological threats, and volunteer training. Collabora- tions between the Centers for Public Health Preparedness, CDC, and the National Association of County and City Health Officials are encouraging preparedness learning for public health workers in local governments.

Laboratory technologists are a fundamental part of the infec- tious disease disaster response team. Timely surveillance, detec- tion, and diagnosis are all dependent on laboratory services and can reduce transmission and disease severity during an infec- tious disease disaster. Chronic underfunding has left many public health laboratories understaffed. As demonstrated by the 1999 West Nile virus emergence, 2001 anthrax attacks, and 2003 SARS pandemic, the laboratory workforce can quickly become over- whelmed with samples. The Association of Public Health Labora- tories Emergency Preparedness and Response Program is charged with preparing laboratories for the increased demand of services in the event of a major disaster. The U.S. CDC implemented the Laboratory Response Network in 1999 to act as a networking platform for laboratories (local, state, federal, international, mil- itary, veterinary, and agricultural) in response to terrorism. This role has since been expanded to include EIDs and other public health emergencies.

The public health workforce is expected to provide accurate information to the general public. Such timely and reliable data are a vital resource for control of an epidemic. Public health telephone hotlines are a common mechanism to disseminate information and to answer specific questions. Disaster plans do not, however, always consider the volume of calls that an infor- mation hotline receives. Over 316,000 calls were placed to the Toronto SARS hotline, which was established the day after the first Toronto SARS case was announced at a press conference. Almost 60% of the callers selected the “listen to recorded infor- mation” option. Of the calls in which the “speak to a staff per- son” option was selected, almost 80% (104,852 calls) were not

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answered by a staff member.34 This number illustrates the over- whelming burden of responsibilities that can be associated with infectious disease disasters. Case numbers alone do not always correlate with workload.

Public Safety Workforce First responders such as law enforcement, firefighters, and

emergency medical services are important segments of the pub- lic workforce for management of an infectious disease disaster. These workers will be involved in the distribution of resources, crowd control at mass gatherings, the transfer of patients, and any criminal investigation resulting from a bioterrorist attack. In some countries, first responders have the advantage of extensive ICS training and experience; however, as outlined previously, biological incidents are unique in many facets. As one of the pri- mary interfaces with the general public, first responders are at risk for exposure to infectious agents. Jurisdictions must determine in advance how best to protect first responders in the event of a contagious infectious disease disaster. The U.S. CDC website pro- vides information for state, local, and tribal public health direc- tors, and for first responders with respect to emergency response after a biological incident. These recommendations include use of PPE by first responders and suggestions for the handling of contaminated mail or containers. Preparedness also includes an understanding of public health law with respect to quarantine orders and other public movement restrictions, and plans for enforcing these orders.

Healthcare Facility Workforce A component of NIMS hospital compliance in the U.S. is

workforce training in core competencies so that hospital person- nel will be able to function in a coordinated fashion during a disaster. The U.S. CDC found that the ICS format for disaster response was critical for providing stable and continuous action after Hurricane Katrina. As a result, the CDC pandemic pre- paredness plan uses the ICS to structure stable functioning dur- ing a prolonged disaster scenario with high staff turnover. Hospi- tal ICS plans for an infectious disease disaster should account for reduced workforce capacity as the disaster progresses due to ill- ness, absence to care for ill family members, refusal to work, and psychological stress. In that regard, healthcare workers should be trained in advance to understand possible implications of a con- tagious infectious disease disaster and methods to contain the disease. This training should include proper use of PPE, duty- to-care expectations, and infection control practices. Workforce preparedness must also address psychological consequences of a prolonged disaster. Recent disasters have demonstrated that the toll on those expected to respond is significant and this stress has usually not received adequate attention. This is especially important when the workforce is already understaffed.

International Workforce Infectious diseases affect more people in developing nations

than in other areas of the world. An underdeveloped and under- staffed public health workforce partly contributes to this poor outcome. Augmenting fields such as epidemiology and infec- tion control in these nations can reduce human suffering and increase detection of emerging pathogens and impending pan- demics. International partnerships among aid organizations, government agencies, and industries have resulted in programs to develop global information networks and workforce alliances to train public health workers in developing countries. The WHO’s

Knowledge Management for Public Health and Global Health Workforce Alliance programs are two examples of international efforts to improve workforce capacity and training in developing nations.

Response Communications

Many aspects of successful management of an infectious disease disaster are dependent on timely and accurate communications between different stakeholders. Examples of such aspects include surveillance, implementation of scientific advances, resource allocations, and delivery of assistance.

International Communication As previously outlined, infectious disease disasters and

emerging new pathogens can rapidly become global in nature. Communication among governments and agencies is fundamen- tal to limiting the extent of an infectious disease disaster. The initial delay in disclosure of a new severe respiratory disease to the world was a likely factor in the global spread of SARS. Once it was clear a new disease had emerged, the international response demonstrated unprecedented cooperation and com- munication. The WHO, facilitated by the Global Outbreak Alert and Response Network, established secure communication net- works and websites for the daily exchange of information on surveillance, epidemiology, and disease characteristics. The util- ity of this networking system was nowhere more evident than in the discovery of the etiological agent. The Laboratory Network, which consisted of 11 laboratories in nine countries, shared data and information. Together, they identified the causative agent of SARS, sequenced its genome, and developed diagnostic tests, all in a matter of weeks. These laboratories were already in com- munication prior to the SARS pandemic via the well-established WHO Influenza Surveillance Network, substantiating the value of ongoing partnerships.

National Response Communication Communication between jurisdictions and between levels of

government is vital during an infectious disease disaster due to the transmissibility of the agent. It can be the difference between a contained localized outbreak and a national epidemic. As an example, the U.S. federal communication response dur- ing a national incident is coordinated by the National Commu- nications System through NRF Emergency Support Functions. Unlike many other disasters, communications interoperability will likely remain intact during an infectious disease disaster. This is in contrast to the situation during Hurricane Katrina, where widespread physical disruption of communication systems made information exchange between response teams difficult. With- out a distinct starting point for the biological incident, however, extensive and formal interagency and intergovernmental com- munication through the NRF may be delayed. This could under- mine unified command and result in multiple and disparate efforts toward similar goals. Even in nondisaster situations, past experiences suggest that poor communication results in conflict- ing actions. For example, during the 2004 U.S. influenza vaccine shortage, agencies at different governmental levels recommended vaccination of different age groups.35

Communication with the Public Communication of disease and containment information to

the community by the public health system can determine, to

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a large degree, the extent of an epidemic. In fact, the WHO held the first Expert Consultation on Outbreak Communication symposium in Singapore in 2004 to discuss risk communication to the public. It is widely agreed that providing the public with accurate and timely information is necessary to prevent spread of the infectious agent. Yet, these tasks are usually very difficult because the information may change as the epidemic unfolds. Inconsistent messages may be viewed as untrustworthy.

The media is a very powerful tool for disseminating infor- mation. In a survey of people quarantined in Toronto during the SARS epidemic, more people claimed that they got helpful information on the quarantine orders from the media than from public health officials or from their healthcare providers. Good working relationships between health department public rela- tions liaisons and local news stations before an incident occurs can encourage cooperation during an outbreak. In a large dis- aster, it may be necessary to establish an information center to coordinate messages for the public. In addition to the disaster itself, the media will also be reporting on the management of the emergency.36 Some decisions will need to be explained or justified. In any case, as defined by the ICS structure, a credible spokesperson should be selected as the point of contact with the media to ensure delivery of consistent and accurate messages to the public.

Resource Management

In a biological incident, critical resources are needed for detection of the pathogen in the community and for appropriate patient care. Yet, real outbreaks from the past and mock tabletop pre- paredness exercises have ascertained that resources in these areas will be limited.

National Resources Within the U.S., HHS and the CDC maintain the Strategic

National Stockpile ([SNS] formerly known as the National Phar- maceutical Stockpile). The SNS is a supply of critical resources that includes antibiotics, antitoxins, ventilators, N95 respirators, and medical equipment for use in the event of a public health emergency. The CDC distributes SNS resources to supplement local capabilities on request from the governors of affected states and on assessment of need. Aid is in the form of 12-hour Push Packages and Vendor Managed Inventory. The 12-hour Push Packages are designed for distribution of nonspecific critical resources from regional warehouses within 12 hours of fed- eral approval of allocation. The Vendor Managed Inventory sup- plies additional and more specific resources within 24–36 hours directly from pharmaceutical companies; the CDC may choose to supply Vendor Managed Inventory instead of a Push Package. The CDC will send a Technical Advisory Response Unit to assist in receiving, organizing, and distributing the supplies.

The SNS is an extensive cache, but insufficient for a cata- strophic disaster effecting multiple jurisdictions. A large infec- tious disease disaster, such as a bioterrorist attack, is an example of an event that will affect many areas at one time. The CDC may have to prioritize which states receive aid from the SNS based on severity of the outbreak. Some SNS resources may even be reserved in the event of a second attack. Furthermore, the 12-hour response time refers to distribution from federal stocks to state authorities; it is up to the states to then determine which localities will receive supplemental aid. Given all of these circum- stances, hospitals should stockpile at least a 48-hour supply of

PPE and drugs likely to be used during a mass casualty infectious disease event. A 3–7-day supply may be necessary in the event of a large or widespread disaster.

Hospital Resources A large biological attack or epidemic could result in hundreds

of people a day presenting to hospital emergency departments during peak disease incidence. As the number of ill patients increases, hospital critical care providers will have to assess re- source capacity and determine allocation procedures to save the most numbers of lives instead of focusing the majority of resources on a few critically ill patients. This is a difficult task because intensive critical care for the very ill in nondisaster situ- ations often results in improved outcomes.

As discussed previously, hospital plans must include pro- visions for isolating infectious patients. These should include requirements for beds, equipment, and staff dedicated for that purpose. The availability of mechanical ventilators is a particular concern during an infectious disease emergency. Many microbial pathogens cause respiratory complications that require mechan- ical ventilation. Yet preparedness assessments have demonstrated that hospitals cannot accommodate ventilation for all patients, even operating under surge capacity guidelines. For example, during a Minnesota drill, regional vendors could only provide 16 extra ventilators.37 Proper allocation of resources is also a function of knowing what resources are available. An up-to- date list of available staffed beds, ventilators, and other limited resources can help with the triage process.

The hospital infectious disease triage system is an important process in quickly determining patient health and susceptibility status. People efficiently and accurately categorized as “suscep- tible,” “exposed and/or infectious,” or “immune” (due to vacci- nation or prior recovery from the disease) can receive the appro- priate management with minimal suboptimal use of resources.38

In the midst of a disaster, the tendency is to either overclassify people as “exposed” or to protect individuals who are at minimal risk. Both of these situations can result in increased numbers of people unnecessarily using limited hospital resources.

Allocation of Resources Preparedness plans need to include guidelines for resource

allocation in the event that supplies are limited. In other words, algorithms are needed to help identify which patients may not qualify for treatment. Making these decisions at the time of an infectious disease disaster without prior consideration can lead to heightened confusion among providers, contention among policymakers, and anger among the public. Legal, social, and political factors will be as much a part of the decision-making process as patient care.

Most agree that to save the most lives, the patients most likely to survive (that is, the least critically ill) should be treated with limited resources first. Whatever system is adopted, administra- tion must be equitable and transparent to all patients and to the public. One mechanism to promote the just allocation of lim- ited resources is to numerically code the survivability of patients based on clinical assessment. Resource distribution is then based on patient scores.

A Specific Case: 2009 H1N1 Pandemic Influenza and Resource Availability

For many years prior to the emergence of the novel influenza A (H1N1) virus in April 2009, the threat of pandemic influenza

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was often used to examine resource availability in public health. The 2009 novel H1N1 event (declared a pandemic by the WHO on June 11) highlighted that disease emergence characteristics can be unpredictable despite well-informed “best guesses:” viral emergence and disease were first detected in North America, not Asia; the pandemic virus was a novel H1N1 quadruple reas- sortant of swine, human and avian genes, not (yet) a highly pathogenic H5N1 avian virus with increased transmissibility in humans; transmission and disease continued during the summer months in the United States; and world-wide disease severity during the initial wave (at the time of this writing) was mild or moderate with low mortality rates. Unlike disease transmission and global spread, in June 2009 disease severity was not offi- cially factored into the decision to elevate the pandemic alert phase, but this pandemic demonstrated that concern for public overreaction and for response activities tied to elevation of alerts necessitated a carefully worded declaration statement addressing that disease was moderate at that time. In addition, it caused the WHO to rethink the definitions of the alert phases.

In the United States, the initial wave of the 2009 H1N1 pandemic illustrated some of the suspected resource challenges of a novel disease outbreak, including increased volumes of patients in emergency departments, management of changing recommendations and information overload, scarcity of PPE (e.g., requirements for and availability of surgical masks and N95 respirators), viral resistance to existing therapeutics, hos- pital employee issues (e.g., absence due to influenza-like illness, wage compensation for absence after exposure, fatigue), avail- ability of diagnostics, and lack of a vaccine. Mass vaccination may be the best strategy for protecting a susceptible population from a second (and perhaps more severe) wave of H1N1 dis- ease, but production limitations may not support timely vaccine availability. Even if pandemic influenza vaccine becomes avail- able, production capabilities may only supply about 14% of the worldwide population.39 The anticipation of a second wave of H1N1 disease in the fall of 2009 coupled with the arrival of sea- sonal influenza led response stakeholders, such as the American College of Emergency Physicians, to issue guidance on the nec- essary resource and surge capabilities for management of novel H1N1 outbreaks.40

The 2009 pandemic marked the highly unusual situation where two viruses co-existed in elevated phases in the WHO pandemic alert system (novel H1N1 at pandemic level and avian H5N1 at phase 3). Viral unpredictability precludes definitive expectations of a “double influenza pandemic.” Nonetheless, such a situation has serious consequences on response capa- bilities; robust pandemic preparedness is especially important for resource management, continuity of operations and patient care.

Preparedness Practice Exercises

Infectious disease disasters are rare events, yet a state of compla- cency or underpreparedness by response stakeholders can result in increased casualties when one does occur. Preparedness is more than just having meetings and written plans. Practice exer- cises are the current state of the art in testing the readiness of response systems and in identifying areas that need reinforce- ment.

Some exercises are supplements to didactic lessons at insti- tutions of higher learning, such as nursing and medical schools. Nurses and physicians may be the first to recognize that an

infectious disease disaster is looming and/or they will be on the frontline of the response. It follows then that nursing and medical students should receive practice in the mechanics of the response during professional training. The exercises are usually in the form of case scenario discussions that address the clini- cal, operational, and ethical issues of infectious diseases disaster management.

Policymakers, resource managers, public health depart- ments, first responders, and healthcare facilities often use table- top exercises and drills to assess preparedness. These types of activities are useful for practicing coordination of efforts within and between different parties. The exercises usually involve the mock release of a biological agent such as the smallpox virus, with informational updates given by the exercise administrators to participants as the disaster unfolds. Factors such as resource availability and allocation, protection of healthcare workers, and public unrest are usually components of the exercise. Table 6.7 lists some of the criteria typically considered for the development of a practice exercise.

Since the anthrax attacks of 2001 and the 2003 SARS outbreak, regional preparedness drills are now commonplace throughout the world. In the U.S., there have been large-scale national disaster exercises such as Dark Winter and TOPOFF (for “top officials”) 1, 2, 3, 4, and 5 starting even prior to 2001. These congressionally mandated exercises were designed to examine national preparedness. They involved officials and responders from all levels of government. All of these exercises substantiated the validity and importance of the preparedness factors that are outlined in this section. For example, TOPOFF 4, which occurred in October 2007, had over 15,000 participants and included the U.S. territory of Guam. It was designed to assess the response to multiple coordinated attacks with a Radiological Dispersal Device. TOPOFF 3, which took place in April 2005, included a bioterrorism component and participation from Canada and the U.K. It was the first national practice of a response based on implementation of the NRF (then known as the National Response Plan) and NIMS in the capacity of the Homeland Security Operations Center. Concerns raised by the DHS Office of Inspector General41 after completion of the exercise included 1) insufficient understanding and training of participants on NRF and NIMS procedures, which resulted in “bureaucrat confusion” and operations under multiple different protocols, 2) confusion over the declaration of an Incident of National Sig- nificance and the consequences of such an action, 3) information collection and reporting, 4) inadequate collaborations between government and the private sector, 5) the high cost of TOPOFF 3 to participating states, and, importantly, 6) repeated weaknesses from TOPOFF 2.

Although not really “drills,” recent outbreaks, epidemics, and events are arguably the most appropriate tools for assessing dis- aster responses. Public reaction, media relations, and interagency communication in a high-pressure situation are components not easily reproduced in an exercise. Response limitations in recent events such as the 2001 anthrax attacks (e.g., laboratory capac- ity), the 2003 SARS pandemic (e.g., contact tracing, implemen- tation of quarantine, and healthcare worker safety) and Hurri- cane Katrina in 2005 (e.g., interagency communication) serve as reminders that certain aspects of preparedness plans are consis- tently deficient. Even local outbreaks of food-borne illness can inform health departments on areas in need of improvement. For exercises to be useful to a jurisdiction, government, or institu- tion, they need to occur at regular intervals. Policies will change

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Table 6.7: Considerations for Practice Exercises∗

Participants ■ Health departments/Public health ■ Government officials (local, state, federal) ■ Hospital workers

Management Patient care providers Laboratory technologists Epidemiologists/Infection control Pharmacists Health information management Support personnel (e.g., housekeeping, security)

■ Law enforcement ■ First responders

Emergency medical services Fire

■ Media representatives ■ U.S. Federal Bureau of Investigation and equivalent in other

countries (bioterrorism exercises) Areas for response assessment ■ Resource availability

Hospital patient care areas and supplies Therapeutics and vaccines Personal protective equipment Personnel

■ Resource allocation ■ Response coordination/Incident Command ■ Infection Control

Spread of the agent through the community Protection of healthcare workers and responders

■ Communication Interagency Among jurisdictions or regions Among levels of government Media relations/Information to public

■ Triage ■ Information management ■ Personnel management

Within facilities and agencies Mobilized for large-scale action (vaccine distribution,

epidemiology) ■ Management of public reaction

Public fear Civil unrest Mass gatherings for resources

■ Psychological ramifications Response personnel Public

■ Understanding of legal implications of decisions ■ Cost of implementing decisions Evaluation of the practice exercise ■ Assessment of whether processes and outcomes of the response

effort met goals ■ Comparison of evaluation to previous exercises ■ Cost of the exercise

∗ Adapted from Bardia

a Bardi J. Aftermath of a hypothetical smallpox disaster. Emerg Infect Dis. 1999;5(4):547–551.

over time due to data from previous exercises and from new legislation. In addition, personnel turnover necessitates repeated practices so that new employees can function within the system. The utility of the exercises is also contingent on proper evalu- ation after they are completed. An exercise with flawed design

and/or execution can lead to a false sense of preparedness. For example, participants in the TOPOFF 3 exercise noted that fed- eral assistance was provided in an unrealistically fast manner and may not correspond to the timing in an actual disaster.

Modeling

Given the rarity of infectious disease disasters, a number of math- ematical models are being developed for use as prediction and forecasting tools. Models use existing data from previous out- breaks, epidemics, or pandemics to provide insight into putative future transmissions of infectious diseases and/or ramifications of preparedness decisions. This is important because the process of designing and interpreting models can serve as a guide for dis- cussions on the variables and assumptions involved in controlling disease. The uncertainty regarding use of various inclusion and exclusion parameters and the potential errors in selection of data values brings into question the significance of the models.

Epidemic emergence models using climatic data have been developed with success for V. cholerae O139, a pathogen endemic to certain regions of the world.42 Modeling of novel or rare pathogens, such as pandemic influenza or intentionally released smallpox, is more problematic. Here, specific characteristics of the agent (transmissibility or drug resistance) and the host (sus- ceptibility, super spreaders, public reaction and compliance) are unknown and must be assumed.

Modeling is also used for preparedness plans to determine how decisions will affect the progression of the epidemic. Mod- els related to resource allocation, antimicrobial use, vaccina- tion strategies, health economic implications, and public control (quarantine, isolation, social distancing) have all been pub- lished.43–47 How to best validate these models (and the decisions they support) and incorporate their recommendations into the formulation or optimization of preparedness plans remains a challenge.

Evaluation

Since 2001, many countries have spent large amounts of money on public health preparedness for a biological event. For exam- ple, the U.S. has spent billions of dollars on surveillance, work- force preparedness, response strategies, and exercises and drills in preparation for an attack using biological weapons. Formal evaluation of these activities is crucial to ensuring that outcomes are properly reviewed and that funding is being used effectively. This mandates more than the simple creation and publication of after-action reports. Preparedness programs should be designed with the inclusion of specific evaluation components to deter- mine empirically whether goals are being met and provide data for improvements. The type of evaluation is critical because some assessment questions may give a skewed sense of readiness. For example, in assessing a workforce readiness training program, asking whether or not people are trained (a structural measure) is different from asking how well employees perform their duties after training (a process measure) or even if the training was suc- cessful in reducing the morbidity and mortality of an infectious disease disaster (an outcome measure). This last type of assess- ment is challenging given the rarity of infectious disease disasters and the difficulty of defining “success.”48

The complexity of preparing for infectious disease disas- ters lies in the unknown nature of future threats. Because of this, many individuals involved in the response may not agree

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on the necessity and requirements for effective preparedness plans. This is particularly true for bioterrorism preparedness, because the perceptions of the necessity for such specific plans vary widely.49,50 For example, the campaign in the U.S. in 2003 to vaccinate 500,000 healthcare workers against smallpox met with very low compliance. This was due, at least in part, to per- ceptions that the threat of a smallpox bioterrorist attack was low and concerns over the unknown safety of the vaccine in adults.51 Evidence-based assessments of the needs and priorities of response preparedness efforts and the probability of success (from sociological and scientific perspectives) are critical to pre- venting this type of program collapse. This is particularly impor- tant because the failure of these large programs causes the public to question the utility and funding of any EID preparedness initiative.

RECOMMENDATIONS FOR FURTHER RESEARCH

As a better understanding of the relationship between humans and the microbial world is gained, the war analogy in approach- ing EID management has become insufficient.52 The traditional paradigm regarded pathogens as enemies to be battled as they emerged. It is clear, however, that relying on the current antimi- crobial arsenal to react to EIDs is proving inadequate. With the exception of postexposure prophylaxis, this is predominantly a treatment strategy for those who have already developed dis- ease. Preventing acquisition of infection or disease is preferable to avert potential disaster situations. There have been successes with preventive mechanisms, such as vaccines to specific infec- tious diseases agents; however, the diversity of EIDs and the potential for microbial adaptation and change precludes using current strategies against all known pathogens, to say nothing of the still undiscovered or yet-to-emerge agents.

The emergence of infectious diseases, largely fueled by human practices, still pose worldwide disaster threats. Immediate needs to expand the local and global public health infrastructure and workforce are obvious. The ultimate future of infectious dis- eases management rests on improving two broad but interrelated areas:

1) Preparedness strategies that surpass the usual unresolved obstacles by promoting multidisciplinary program design, and by substantiating early surveillance/detection and pre- vention of disease;

2) Research into novel countermeasure development, host– microbe relationships, host–immune responses, surveillance tools, and analysis of how behaviors of the human host and perturbations of the environment (whether at the macro- or micromolecular level) affect infectious diseases emergence. These essentially encompass a fresh perspective reevaluation of the approach regarding the understanding of the epidemi- ology of infectious diseases.

Preparedness

Preparedness Strategies Repeated drills are used to determine areas for preparedness

plan improvements; however, the usefulness of drills dimin- ishes when identified obstacles are not addressed. Areas con- sistently identified for further improvement include resource allocation, communication between response stakeholders, and

understanding of governmental roles. Current templates for planning need modification to first address why these “lessons learned” are not, or cannot be, actually implemented. This neces- sitates the study (not merely discussion) of the barriers to incor- poration of findings from previous drills and disasters by multi- disciplinary teams that include social scientists, communications experts, and human factors specialists. Ultimately, drills should be used as a rehearsal tool for workforce training (i.e., to identify improvement goals on an individual basis), not as a mechanism for developing preparedness plans.

EID Surveillance Although improved response preparedness is reassuring, pre-

venting disease transmission will do much to reduce the depen- dence on limited resources and other preparedness obstacles. EID management needs to be changed beyond the state of rely- ing on disease treatment when cases appear at the hospital doors. In essence, it must move from the conventional reactionary EID response to a more proactive approach.53 Improving early EID detection can reduce the “incident threshold” and expedite agent characterization, assessment of response needs, and education of the public. This must be a global effort. Although new agents can emerge from any area, developing countries bear the bur- den of global infectious diseases incidence and the likelihood of witnessing the development of new pathogens. The developed world has a responsibility to provide assistance in surveillance for both humanitarian reasons and the need for self-protection. Great strides have been made in global surveillance, especially after the infectious disease events of the new millennium, but there are still political, social, and economic obstacles to further advancement.

In addition to improving methods for achieving better surveillance, what is monitored needs to be broadened beyond human symptom and disease reports. Many EIDs are zoonoses; past evidence shows that understanding animal infectious dis- ease trends can benefit human health. For example, the first West Nile virus encephalitis cases in North America were preceded by disease in birds. Linking animal disease surveillance (includ- ing zoological, agricultural, wild, and companion animals) with human disease surveillance clearinghouses can alert public health officials sooner to potential human infectious disease disasters, whether global in nature or constrained to a small location. The specificities of such tactics are complicated, given the current inconsistencies in animal disease surveillance and reporting and the unproven value of many human disease surveillance sys- tems. In the U.S. for example, the National Biosurveillance Inte- gration System aims to coordinate human, animal, and plant surveillance. Much of the work will entail assessing the scope of surveillance necessary and standardizing surveillance systems for uniformity to facilitate data integration. The ultimate ben- efit of putative zoonoses detection is the interruption of agent transmission to humans to prevent disease.

Research

Basic Research The understanding of pathogens has been transformed by

genomics and proteomics, fields of molecular biology that study the overall functions and regulation of the genes and proteins of an organism in an environment. These technologies allow scientists to identify disease-causing agents and comprehensively characterize microbial pathogenic mechanisms in a fraction of

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the time than in previous decades. Future efforts must include the development of technologies to translate this knowledge into functional applications such as rapid screening of people and/or animals during an EID disaster, the development of sensitive handheld devices for remote screening applications, and more rapid determination of antimicrobial resistances and applica- tion of therapies. Chapter 11 further describes future goals in molecular surveillance research.

For effective EID management, other areas of basic research must be enhanced to complement the more common agent- specific programs. Namely, there is a need to expand research on diverse biological disciplines associated with zoonotic and vector-borne diseases, such as reservoir ecology and entomology. Ideally, these specialties would be housed in interdisciplinary aca- demic EID departments that include infectious diseases, molec- ular biology, and conservation medicine experts to foster a col- laborative atmosphere.

Drug and Vaccine Development Improved pharmaceuticals alone will not be adequate to

change the burden of EIDs on society, but they have an important role in mitigating disease severity, human suffering, and infec- tious agent transmission. The need and incentives for antimicro- bial drug development has already been outlined. The future lies in the discovery of novel targets and mechanisms active against a broad spectrum of agents. This requires a more comprehen- sive understanding of host–pathogen relationships: how the host recognizes an invading pathogen, how pathogens evade host defenses, how hosts and microbes interact in nonpathogenic relationships (symbiosis), and how host–immune responses to pathogens can be modulated by drugs or by beneficial bacteria.

Vaccine development is making revolutionary advances. Sci- entists are on the brink of unlocking the secrets of improving vac- cine efficacy by targeting both the innate and adaptive immune response.54 DNA vaccines hold promise as future EID coun- termeasures because they can be designed and manufactured relatively rapidly, they can induce cross-strain immunity, and they can be administered by different routes.55 Progress must be made in moving these types of technologies to product devel- opment and clinical trials so that options are in place before the next EID.

The international community must take a more collabora- tive approach to drug and vaccine design for EIDs. Nowhere is this more evident than in the case of pandemic influenza vac- cine. Current production capabilities may limit the number of courses available during an infectious disease disaster. Scientific research is necessary to 1) develop rapid in vitro methods for vac- cine component production, 2) increase vaccine efficacy at lower doses, 3) investigate less-specific vaccines that can be made and stockpiled prior to a pandemic, and 4) increase the shelf-life of vaccines. Advances in all four of these areas can benefit both influenza pandemic preparedness and vaccinology in general. The WHO has convened meetings with international stakehold- ers to formulate plans for increasing the international produc- tion capacity of influenza vaccine. Such plans will need to address international differences in complicated issues such as produc- tion regulations, acceptable clinical safety data, and intellectual property.

EID Surveillance Research A more expansive approach to surveillance that encompasses

monitoring beyond human and animal health is under investi-

gation. Sometimes termed “conservation medicine,” it utilizes interdisciplinary networks that examine the ecology of micro- bial interactions with animals, plants, and humans in the con- text of the drivers of disease emergence.56 These networks should include the expertise of health workers, veterinarians, plant biol- ogists, epidemiologists, ecologists, climatologists, and conser- vation biologists. Environmental specialists and global geolo- gists must be involved in such endeavors to ensure inclusion of environmental aspects that may affect EIDs. Computational and theoretical biologists, and epidemiologists with expertise in transmission, host–agent interaction, host–environment inter- action, and agent–environment interaction, need to develop cooperative research programs among themselves and with other specialists. The goal of such collaboration is to produce, and more importantly, validate, predictive models of disease occur- rence. This holistic approach to surveillance is exemplified by geographical information systems that integrate infectious dis- ease incidence, prevalence, and distribution data with satellite environmental data to predict disease emergence in other loca- tions with similar conditions.57

The ultimate goal is the capability to predict human EIDs before they occur or at least to recognize an emergence sooner. These types of broad surveillance tools that include environ- mental components have been used for years by plant biolo- gists to predict disease emergence in agricultural crops. Indeed, the oft-used basic epidemiological triangle of host, agent, and environmental interactions described earlier in this chapter was officially conceptualized decades ago by plant biologists.58 The link between environmental factors and plant diseases may be obvious, but the time is overdue to integrate this same approach to understanding human infectious diseases.

Infectious disease disaster medicine is itself a growing field and has been the focus of extensive preparedness efforts. Further research on the impact of politics, international relations, social behavior, and public health policies on EID disaster management is warranted to develop sound and realistic action plans. As noted throughout the chapter, this multidisciplinary focus of effort toward the fields of infectious diseases biology and epidemiology is a nascent application that holds promise for the future of both infectious diseases and disaster medicine.

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