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APPENDIX E
Biological Terrorism

Russ Zajtchuk and David Franz1

The thought of an outbreak of disease caused by the intentional release of a pathogen or toxin in an American city was alien just 10 years ago. Many people believed that biological warfare was only in the military’s imagination, perhaps to be faced by soldiers on a faraway battlefield, if at all. The “anthrax letters” and the resulting deaths from inhalation anthrax have changed that perception.

The national, state, and local governments in the United States are preparing for what is now called “not if, but when and how extensive” biological terrorism. In contrast to the acute onset and first responder focus with a chemical attack, in a bioterrorist attack, the physician and the hospital will be at the center of the fray. Whether the attack is a hoax, a small foodborne outbreak, a lethal aerosol cloud moving silently through a city at night, or the introduction of contagious disease, the physician who understands threat agent characteristics and diagnostic and treatment options and who thinks like an epidemiologist will have the greatest success in limiting the impact of the attack. As individual health care providers, we must add the exotic agents to our diagnostic differentials. Hospital administrators must consider augmenting diagnostic capabilities and surveillance programs and even making infrastructure modifications in preparation for the treatment of victims of bioterrorism. Above all, we must all educate ourselves. If done correctly, preparation for a biological attack will be as “dual use” as the facility that produced the weapon. A sound public health infrastructure, which includes all of us and our resources, will serve this nation well for the control of the disease, no matter what the cause of the disease.



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Terrorism: Reducing Vulnerabilities and Improving Responses - U.S.-Russian Workshop Proceedings APPENDIX E Biological Terrorism Russ Zajtchuk and David Franz1 The thought of an outbreak of disease caused by the intentional release of a pathogen or toxin in an American city was alien just 10 years ago. Many people believed that biological warfare was only in the military’s imagination, perhaps to be faced by soldiers on a faraway battlefield, if at all. The “anthrax letters” and the resulting deaths from inhalation anthrax have changed that perception. The national, state, and local governments in the United States are preparing for what is now called “not if, but when and how extensive” biological terrorism. In contrast to the acute onset and first responder focus with a chemical attack, in a bioterrorist attack, the physician and the hospital will be at the center of the fray. Whether the attack is a hoax, a small foodborne outbreak, a lethal aerosol cloud moving silently through a city at night, or the introduction of contagious disease, the physician who understands threat agent characteristics and diagnostic and treatment options and who thinks like an epidemiologist will have the greatest success in limiting the impact of the attack. As individual health care providers, we must add the exotic agents to our diagnostic differentials. Hospital administrators must consider augmenting diagnostic capabilities and surveillance programs and even making infrastructure modifications in preparation for the treatment of victims of bioterrorism. Above all, we must all educate ourselves. If done correctly, preparation for a biological attack will be as “dual use” as the facility that produced the weapon. A sound public health infrastructure, which includes all of us and our resources, will serve this nation well for the control of the disease, no matter what the cause of the disease.

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Terrorism: Reducing Vulnerabilities and Improving Responses - U.S.-Russian Workshop Proceedings INTRODUCTION Before 1990, little thought was given to the possibility of biological warfare or a biological terrorist attack on U.S. cities. Even as recently as 1997, the U.S. Department of Defense spent approximately $137 million on biodefense to protect the deployed force, while academia, industry, local governments, and the rest of the federal government were oblivious to—and in some cases, doubtful about—the threat of biological warfare.2 In fiscal year 2000, the United States committed more than $1.5 billion to military biodefense and another $1 billion to domestic preparedness for biological attack. The responsibility for research, development, policy, and planning is now spread among the Departments of Justice, Health and Human Services, Defense, and Energy, with the Department of Justice responsible for crisis management (intelligence, law enforcement, and education of first responders) and the Department of Health and Human Services responsible for consequence management (surveillance, epidemiology, reference laboratory and field diagnostics, triage, and postexposure prophylaxis and therapy). Anthrax letters have resulted in American deaths from inhalation anthrax, the first since 1978. Although the loss of life has been minimal—we lose 20,000 to 80,000 Americans to influenza each year—the psychological and economic effects have been significant. Before September 2001, our emergency responders were dealing with about 200 biological hoaxes each year, up from approximately 20 to 30 in 1997. In just weeks since the anthrax letters, we have seen many thousands of biological hoaxes and copycat letter attacks. THE DUAL-USE NATURE OF BIOLOGICAL WARFARE PROGRAMS The process of research, development, and production of biological weapons is an extremely difficult intelligence target because legitimate vaccine and agricultural production facilities can be used to make illegal biological weapon agents. Basic research can be done in academic, industrial, or government public health laboratories. The scale-up of agent lots can be done in pharmaceutical or agricultural facilities. Weaponization and field testing may be more difficult to disguise, but the previous Iraqi regime successfully tested aerosol dissemination equipment on aircraft by flying modified crop-dusting equipment out of a cropdusting airfield. Although the previous Iraqi regime had successfully developed and field-tested biological agents (Bacillus anthracis, botulinum toxin serotype A, and aflatoxin) in bombs, rockets, and agricultural sprayers on conventional aircraft, our best information suggests that they were nothing more than high-level bioterrorists.3

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Terrorism: Reducing Vulnerabilities and Improving Responses - U.S.-Russian Workshop Proceedings TODAY’S AND TOMORROW’S THREATS TO OUR CITIES Classic Cold War Agents During the cold war, which reached its peak in the 1980s, the Soviet Union and the United States and its allies, Great Britain and Canada, developed biological weapons. These nations’ programs were developed independently as highly classified endeavors. Yet, of the thousands of bacteria, viruses, and biological toxins available in nature, the proliferators typically selected fewer than 20 agents for weaponization—and their lists were strikingly similar. (There is evidence that the Iraqi program agent list was influenced by the previous work of others.) The agents of anthrax, plague, and tularemia were commonly selected bacterial agents throughout the past 60 years. The easily grown and highly infectious encephalitic alphaviruses (for example, Venezuelan equine encephalitis, or VEE) were favorites, and the botulinum toxins were always tried, at least in the beginning of developing programs. The proliferators of the past selected their agents for pathogenicity or toxicity, ease of production into weapons, and stability during production, processing, storage, and dissemination. It is no wonder that anthrax came to the top of everyone’s list. The would-be terrorist is constrained by most of the physical and biological rules that plagued the biological warfare proliferators of the past. To lethally infect 100,000 people in a city, the terrorist must lay down a cloud in a respirable particle size that will allow pulmonary or airway retention of the agent. The cloud must hug the ground and not be dispersed and diluted in the atmosphere as on a warm, sunny day. Although some experts disagree, we believe that to accomplish such a deed efficiently, the terrorist would be dependent on state sponsorship—by a state at least as accomplished as Iraq was in 1999—and would have to use one of the “dirty dozen” agents selected by yesterday’s bioweaponeers. To infect 500 to 1,000 people through the air-handling system of a large office building, the meteorological constraints would be eliminated, but many of the others would remain. Highly Contagious Agents In one type of attack a direct relation between effort by the terrorist and result on the target may not apply. We have said that intent, access to agents, research and development, scale-up, weaponization, testing, and favorable meteorological conditions are necessary for the successful execution of an attack with a respirable biological agent. The highly contagious agents such as variola (smallpox) or an influenza strain similar to that which killed approximately 20 million people in the early 1900s may allow terrorists to accomplish a truly horrific attack with intent and access to the agent only.

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Terrorism: Reducing Vulnerabilities and Improving Responses - U.S.-Russian Workshop Proceedings Biological Toxins Of the hundreds of biological toxins in nature, only a very small number are potent enough to be used. Because they must be delivered as respirable aerosols, a toxin’s utility as a battlefield—or urban—weapon is limited by its potency and ease of production. It is apparent that, ignoring other characteristics, if a toxin is not adequately potent, sufficient quantities cannot be produced to make even one weapon. Because of low potency, hundreds of toxins can be eliminated as ineffective for use as mass casualty weapons in our cities. Certain plant toxins with marginal potency, such as ricin, could be produced in large (ton) quantities. These toxins could possibly be weaponized by a competent organization. At the other extreme, several bacterial toxins are so lethal that mass casualty quantities are measured not in tons but in kilograms, quantities much more easily produced. Such toxins are potential threats to our cities. The botulinum toxins are so potent that lethal aerosol mass casualty weapons could be produced with quantities that are attainable relatively easily with current technology. Botulinum toxin, serotype A, is 10,000 to 100,000 times more potent than most of the well-known chemical warfare agents. THE EPIDEMIOLOGY OF BIOTERRORISM The Attack Assume that an individual or group can obtain a high-quality, talcum powder-like dry agent with adequate viability and release it in one of our cities under the right meteorological conditions and at the right time of day without notice. The result would be a footprint of potential exposure, with high and low concentration eddies caused by buildings and city effect. The extent of exposure would be greatly dependent on time of day, season, weather, and chance. Dose received by those exposed would follow a broad distribution, and for many agents, onset of clinical disease would vary directly with dose and possibly with age and physical condition. Many of the diseases associated with the agents we have discussed present as a flu-like illness. In our society, many individuals would attempt self-medication, and some few who visited their physicians early would be sent home with analgesics, forced fluids, and bed rest. It may not be immediately obvious that there has been a biological attack. We may have to differentiate such an attack from a spontaneous outbreak in an endemic area or a spontaneous epidemic of an emerging or unknown disease. With a spontaneous outbreak, there may be seasonal clues and a gradual increase in incidence and traditional cycles of transmission. With a biological attack, whether aerosol or foodborne, there may be a compressed epidemic curve, even when considering varying exposure doses and differing states of health of the exposed population.

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Terrorism: Reducing Vulnerabilities and Improving Responses - U.S.-Russian Workshop Proceedings Identification of the agent may be difficult and is of critical importance. Without identifying the agent, rational postexposure prophylaxis will be impossible. If a weapon or container is found, samples may be taken directly and delivered to a reference laboratory for analysis. Formulation of a case definition is important for several reasons. During epidemiological investigation, the case definition allows investigators widely separated geographically to use the same criteria in evaluating the extent of the outbreak and the attack rate. It allows the outbreak to be described, and the clinically based definition supports diagnostic and triage efforts even if definitive diagnostic tools are not widely available. The case definition is even more important for investigating a potential biological attack because of the increased likelihood of hysteria and confusion caused by rumor, misinformation, and fear of the unknown. The city that collects good, seasonally adjusted background rates for influenza, gastrointestinal disease, and other common public health threats will be better prepared to identify and describe the unusual outbreak. Description of the Outbreak The outbreak must be described to assist in identifying and caring for victims and for forensic purposes. Circumscribing the footprint of an aerosol attack will be necessary to assist in notifying, testing, and treating the potentially exposed. The aerosol attack differs from traditional insect-borne or patient contact exposure and disease spread. Onset data would be compressed and exposure data, especially for a noncontiguous aerosol, would reflect a snapshot-in-time location map of the victims. Therefore, knowing whether the release occurred during rush hour or at 2:00 a.m. would greatly change the exposure footprint if not the actual cloud footprint. An attack on a city would be complicated by complex wind patterns that prevail among multistory buildings and by the micro-environment produced by unique temperature gradients. Obtaining meteorological information from local airports or weather stations can be helpful. Several government agencies now have computer plume-prediction models, which can also be helpful, if some sense of source and routine meteorological data are available. The investigation of the Sverdlovsk accident, even 20 years after it occurred, benefited from historic meteorological data, and airport weather station data proved useful in confirming that the spores had been windborne.4 Historically, in a disaster, a relatively large percentage of any population leaves their homes and flees. Flight after a biological aerosol attack is, of course, the wrong thing to do. Movement from the area not only complicates the investigation but also takes patients away from help and with contagious agents may facilitate spread of the outbreak. Knowledgeable, respected medical leadership in the city will be needed to appeal to the population for their trust and cooperation with the response personnel.

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Terrorism: Reducing Vulnerabilities and Improving Responses - U.S.-Russian Workshop Proceedings Identification of Exposed Individuals Human beings who have been exposed, even to replicating agents, will not have measurable amounts of the agent in their blood or serum for several days at the earliest, nor will they have a measurable immune response. However, after inhalation exposure of replicating agents or toxins, nasal mucosal swab samples may contain sufficient agent to allow identification by PCR (polymerase chain reaction) or ELISA (enzyme-linked immunosorbent assay). Nasal swab analysis may be useful for anthrax, for example, but not for the alphaviruses or some of the viral hemorrhagic fevers with extremely low infective doses. Treatment and Patient Management Once the agent has been identified, decisions can be made regarding triage and postexposure prophylaxis. Is specific therapy available? How much time do we have to treat primary exposures? Is there a chance of secondary spread? If the causative agent of inhalation anthrax, pneumonic plague, or possibly tularemia, with its 35 percent case-fatality rate, is identified from field or nasal swab samples, a rapid response becomes the first priority. With these agents, postexposure prophylaxis within the first 24 to 48 hours can mean the difference between life and death. If the agent were VEE, much less could be done for individual victims, but mosquito control and equine immunization might be critical. The appropriate response may range from door-to-door treatment teams to simply providing the public good information through the media. If the decision is made to treat the population within the cloud footprint, it may be done door-to-door, at central collection points—schools, churches, or civic centers—or using both approaches. In the aftermath of a terrorist attack, many victims may self-admit to hospitals. City hospitals may have overwhelming admissions and emergency room visits the day of the attack. If the agent used was not life threatening, crowd control procedures may suffice in dealing with large numbers of hospital visits. If the agent causes severe illness or death, hospitals must be prepared to increase capacities by adding beds and reducing routine patient load. Preparation for Biological Attack: What Can a Medical Center Do? It is the physician and the medical facility, not necessarily the paramedics, police, and fire service, that will take the brunt of a biological terrorist attack. The prepared physician, hospital, and medical center have the potential of making an enormous difference in outcome after an attack. Therefore, preparation at this level is critical. Fortunately, much of what should be done in anticipation of a biological terrorist attack is also applicable to any public health disaster or

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Terrorism: Reducing Vulnerabilities and Improving Responses - U.S.-Russian Workshop Proceedings infectious disease outbreak. Sound preparation, like production of biological weapons, is truly dual use. Education and Training At the top of the list of priorities are education and training. Much of what is needed in a hospital or medical center that faces a spike in the patient load after an attack is simple application of the standard principles of medicine with which the professional and support staffs are already intimately familiar. However, if the disease faced is not in the doctor’s differential or the doctor is unaccustomed to thinking about “herd health,” the way ahead may seem fraught with danger. Education and training must include the general characteristics of biological agents versus chemical agents; clinical presentation, diagnosis, prophylaxis, and therapy of the most important diseases; and sample handling, decontamination, and barrier patient care. Training, planning, and drills must prepare the physicians and staff for mass casualty patient treatment, respiratory support for unusual numbers of patients, and distribution of medications or support of the local government in vaccination programs. The engineering staff must be taught to establish improvised containment in patient rooms or suites. To apply the knowledge we already have or to use the facilities already in place in a mass casualty resulting from a biological terrorist attack is the least difficult, least expensive, and probably the most important thing we can do to prepare. Routine Surveillance Although most surveillance programs may be initiated at the national or state level, hospitals and medical centers should consider establishing their own. This is more easily done today than in the past because of automation. For example, large numbers of flu-like illnesses seen at emergency rooms, severe gastrointestinal syndromes, or evidence of an increased caseload of communicable disease or simply nontrauma admissions or even deaths should be cause for taking a second look from an epidemiological view. The pharmacy service might consider monitoring selected antibiotics or antidiarrheal medications and flagging dispensing levels greater than the norm. For a covert attack, surveillance may provide the first indication of an attack. For either a covert or overt attack, a sound surveillance system may help circumscribe the geographic extent of the attack and provide essential information regarding where postexposure prophylaxis and therapy should be initiated. Infrastructure Modifications For biological attack, two categories of modification to the hospital building may be required. The first, related to decontamination and segregation of pa-

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Terrorism: Reducing Vulnerabilities and Improving Responses - U.S.-Russian Workshop Proceedings tients, is probably less important for biological attack than for chemical attack. As described above, patients exposed to a true respirable aerosol may have little or no contamination externally. For most agents that are not highly infectious, simple surface decontamination of the face and nares may be sufficient. The second modification that should be considered is some sort of preparation for dealing with highly contagious or dangerous infectious patients. Fortunately, this might not be necessary for many of the agents that might be selected by the bioterrorist. NOTES 1.   Reprinted from Disease-a-Month, 48, Franz, D.R.; Zajtchuk, R.; Biological Terrorism: Understanding the Threat, Preparation, and Medical Response, 489–568, Copyright (2002) with permission from Elsevier. 2.   U.S. Department of State. 1998. Report of the United States of America to the United Nations Department of Disarmament Affairs. Washington, D.C.: Department of State. 3.   Trevan, T. 1999. Saddam’s secrets: The hunt for Iraq’s hidden weapons. London: Harper Collins. 4.   Meselson, M., J. Guillemin, M. Hugh-Jones, et al. 1994. The Sverdlovsk anthrax outbreak of 1979. Science 266:1202–1208.