Biological Attack

Bioterrorism can be broadly defined as the deliberate use of microbial agents or their toxins as weapons. The broad scope and mounting boldness of worldwide terrorism exemplified by the massive attacks on New York City and Washington, DC, on September 11, 2001, coupled with the apparent willingness of terrorist organizations to acquire and deploy biological weapons, constitute ample evidence that the specter of bioterrorism will continue to pose a global threat.

As in other aspects of daily life and the practice of medicine, in particular, the concept of “risk” is germane to considerations regarding an attack using biological agents. Risk , broadly defined as the probability that exposure to a hazard will lead to a negative consequence, can be accurately calculated for a variety of conditions of public health importance ( Table 79-1 ). However, the quantification of risk as it pertains to bioterrorism is imprecise because accurate assessment of exposure depends on the whims of terrorists, by nature, an unpredictable variable. Although the probability of exposure to a biological attack is statistically low, it is not zero. Because the negative consequences of an attack are potentially catastrophic, an understanding of biological threat agents and a cogent biodefense strategy are important components of disaster medicine.

Table 79-1

U.S. Mortality Risk Analysis *

Heart disease	1 in 397
Cancer	1 in 511
Stroke	1 in 1699
Alzheimer’s	1 in 5752
Motor vehicle accident	1 in 6745
Homicide	1 in 15,440
Drowning	1 in 64,031
Fire	1 in 82,977
Bicycle accident	1 in 376,165
Lightning strike	1 in 4,478,159
Bioterrorism (anthrax)	1 in 56,424,800

* U.S. Population divided by the number of annual deaths for 2000.

Historical perspective

Biological weapons have been used against both military and civilian targets throughout history, perhaps as early as 600 bc . In the fourteenth century, Tatars attempted to use epidemic disease against the defenders of Kaffa, by catapulting plague-infected corpses into the city. British forces gave Native Americans blankets from a smallpox hospital in an attempt to affect the balance of power in the Ohio River Valley in the eighteenth century. In addition to their well-described use of chemical weapons, Axis forces purportedly infected livestock with anthrax and glanders to weaken Allied supply initiatives during World War I. Perhaps the most egregious example of biological warfare involved the Japanese program in occupied Manchuria from 1932 to 1945. Based on survivor accounts and confessions of Japanese participants, thousands of prisoners were murdered in experiments using a variety of virulent pathogens at Unit 731, the code name for a notorious Japanese biological weapons facility.

The United States maintained an active program for the development and testing of offensive biological weapons from the early 1940s until 1969, when the program was terminated by executive order of then President Nixon. Current efforts continue as countermeasures against biological weapons. The Convention on the Prohibition of the Development, Production, and Stockpiling of Biological and Toxin Weapons and on their Destruction (BWC) was ratified in 1972, formally banning the development or use of biological weapons, and assigning enforcement responsibility to the United Nations. Unfortunately, the BWC has not been effective in its stated goals; multiple signatories have violated the terms and spirit of the agreement. The accidental release of aerosolized anthrax spores from a biological weapons plant in the Soviet Union in 1979, with at least 68 human deaths from inhalational anthrax reported downwind, was proven years later to have occurred in the context of offensive weapons production.

Events within the past 30 years have established bioterrorism as a credible and ubiquitous threat: for example, the 1984 incident in The Dalles, Oregon, involving the intentional contamination of restaurant salad bars with Salmonella , by a religious cult attempting to influence a local election. Public fears were additionally heightened by the international events following the Japanese Aum Shinrikyo cult’s sarin attack in Tokyo in 1995, especially after investigations revealed that the group had been experimenting with aerosolized anthrax release from rooftops for several months prior. More recently, UN weapons-inspector findings of significant quantities of weaponized biological compounds in Iraq during the Gulf War and the subsequent aftermath has served as sentinel warnings of a shift in terrorism trends. This trend culminated with the October 2001 anthrax attacks in the United States, which elevated bioterrorism to the forefront of international dialogue and heightened public concerns regarding systemic health care preparation against the threat of biological attacks.

Current practice

Threat Assessment

Biological agents are considered weapons of mass destruction (WMDs) because, as with certain conventional, chemical, and nuclear weapons, their use may result in large-scale morbidity and mortality. A World Health Organization (WHO) model based on the hypothetical effects of the intentional release of 50 kg of aerosolized anthrax spores upwind from a population center of 500,000 (analogous to that of metropolitan Providence, RI) estimated that the agent would disseminate in excess of 20 km downwind and that nearly 200,000 people would be killed or injured by the event. Biological weapons possess unique properties among WMDs. By definition, biological agents are associated with a clinical latency period of days to weeks, in most cases, during which time early detection is quite difficult with currently available technology. Yet, early detection is critical because specific antimicrobial therapy and vaccines are available for the treatment and prevention of illness caused by certain biological weapons. Casualties from other forms of WMDs can generally only be treated by decontamination (with antidotes available for only some types), trauma mitigation, and supportive care. Additionally, the possibility of a biological attack provokes fear and anxiety—“terror”—disproportionate to that seen with other threats, given their often invisible nature.

The goals of bioterrorism are those of terrorism in general: morbidity and mortality among civilian populations, disruption of the societal fabric, and exhaustion or diversion of resources. A successful outcome from a terrorist standpoint may be achieved without furthering all of these aims but instead disrupting daily life. The anthrax attacks in the United States in 2001 evoked significant anxiety and diverted resources from other critical public health activities despite the limited number of casualties. In many cases, the surge capacity of our public health system has been inadequate to deal with the emergency needs, resulting in reform and additional planning after the event.

To be used in large-scale bioterrorism, biological agents must undergo complex processes of production, cultivation, chemical modification, and weaponization. For these reasons, state sponsorship or direct support from governments or organizations with significant resources, contacts, and infrastructure would predictably be required in large-scale events. However, revelations have suggested that some agents may be available on the worldwide black market and in other illicit settings, thus obviating the need for the extensive production process. Although traditionally thought to require an efficient delivery mode, recent events, including the 2001 United States anthrax attacks, demonstrated the devastating results that can be achieved with relatively primitive delivery methods (e.g., high-speed mail-sorting equipment and mailed letters).

Numerous attributes contribute to the selection of a pathogen as a biological weapon: availability or ease of large-scale production, ease of dissemination (usually by the aerosol route), stability of the product in storage, cost, and clinical virulence. The last of these refers to the reliability with which the pathogen causes high mortality, morbidity, or social disruption. The Centers for Disease Control and Prevention (CDC) has prioritized biological-agent threats based on the aforementioned characteristics, and this has influenced current preparation strategies ( Table 79-2 ). Category A agents, considered the highest priority, are associated with high mortality and the greatest potential for major effects on the public health. Category B agents are considered “incapacitating” because of their potential for moderate morbidity but relatively low mortality. Most of the category A and B agents have been experimentally weaponized in the past and thus have proven feasibility. Category C agents include emerging threats and pathogens that may be available for development and weaponization.

Table 79-2

Agents of Concern for Use in Bioterrorism

Microbe or Toxin	Disease
Highest Priority (Category A)
Bacillus anthracis	Anthrax
Variola virus	Smallpox
Yersinia pestis	Plague
Clostridium botulinum	Botulism
Francisella tularensis	Tularemia
Filoviruses	Ebola hemorrhagic fevers and Marburg disease
Arenaviruses	Lassa fever and South American hemorrhagic fevers
Bunyaviruses	Rift Valley fever and Congo-Crimean hemorrhagic fevers
Moderately High Priority (Category B)
Coxiella burnetti	Q fever
Brucella spp.	Brucellosis
Burkholderia mallei	Glanders
Alphaviruses	Viral encephalitis
Ricin	Ricin intoxication
Staphylococcus aures	Staphylococcal toxin illness enterotoxin B
Salmonella spp.	Food- and water-borne gastroenteritis
Shigella dysenteriae	Bacillary dysentery (shigellosis)
Escherichia coli	Gastroenteritis, 0157:H7-induced HUS
Vibrio cholerae	Cholera diarrhea
Cryptosporidium parvum	Cryptosporidiosis
Category C
Hantavirus	Viral hemorrhagic fevers
Flaviviruses	Yellow fever
Mycobacterium tuberculosis	Multidrug-resistant tuberculosis
Miscellaneous
Genetically engineered vaccine-and/or antimicrobial-resistant Category A or B agents
HIV-1
Adenoviruses
Influenza
Rotaviruses
Hybrid pathogens (e.g., smallpox-plague and smallpox-Ebola)

Artenstein AW. Bioterrorism and biodefense. In: Cohen J, Powderly WG, eds. Infectious Diseases . 2nd ed. London: Mosby; 2003:99-107. Used with permission.

Another factor that must be addressed in assessing future bioterrorism risk is the historical record of experimentation with specific pathogens, informed by the corroborated claims of various high-level Soviet defectors and data released from the former offensive weapons programs of the United States and United Kingdom. Information from these sources, combined with the burgeoning fields of molecular biology and genomics, demonstrates that future risk scenarios will likely have to contend with genetically altered and “designer” pathogens intended to bypass current known medical countermeasures or defenses. To this end, a miscellaneous grouping of potential threat agents is added to the extant CDC categories in Table 79-2 . The most cautious approach to assessing risk requires public health officials to remain open to additional and novel possibilities in the setting of a suspected bioterrorism event.

Bioterrorism recognition

Bioterrorist attacks are often insidious. Absent of advance warning or specific intelligence information, clinical illness will likely manifest before the circumstances of a release event are known. For this reason, health care providers are likely to be the first responders and reporting agents of this form of terrorism. This is in contrast to the more familiar scenarios in which police, firefighters, paramedics, and other emergency services personnel are deployed to the scene of an attack with conventional weaponry or a natural disaster. Physicians and other health care workers must therefore maintain a high index of suspicion of bioterrorism, and recognize suggestive epidemiologic clues and clinical features to enhance early recognition and guide initial management of casualties. Early recognition and rapid deployment of specific therapy remains the most effective way to minimize the deleterious effects of bioterrorism on both exposed individuals and public health.

Unfortunately, early recognition is hampered for multiple reasons. As previously discussed, it is likely that the circumstances of any event will only be known in retrospect. Therefore responders may be unable to discern the extent of exposure immediately. Also, terrorists have a nearly unlimited number of targets in most open democratic societies, and it is unrealistic to expect any governing body without detailed intelligence of an impending attack to secure an entire population at all times. Certain sites, such as government institutions, historic landmarks, or large public gatherings, may be predictable targets; however, other facilities may fall victim to bioterrorism. In fact, government data support that businesses and other economic concerns were the main targets of global terrorism during the period from 1996 to 2002. Metropolitan areas are traditionally considered especially vulnerable given the dense populations and already existing public gathering areas such as subways and office buildings. Because of the expansion of suburbs and the commuter lifestyle, as well as the clinical latency period between exposure and symptoms, casualties of bioterrorism are likely to present for medical attention in diverse locations and at varying times after a common exposure. An event in New York City on a Wednesday morning may result in clinically ill persons presenting over the ensuing weekend to a variety of emergency departments within a 60-mile radius. Finally, current modes of transportation ensure that there will be affected persons thousands of miles away, at both national and international locations, related to a single common exposure. This adds layers of complexity to an already complicated management strategy and illustrates the critical importance of surveillance and real-time communication in the response to suspected bioterrorism.

Further hindering the early recognition of bioterrorism is that initial symptoms of a biological weapon may be nonspecific and nondiagnostic. In the absence of a known exposure, many symptomatic persons may not seek medical attention early, or if they do, they may be misdiagnosed as having a viral or flu-like illness. If allowed to progress beyond the early stages, many of these illnesses deteriorate quite rapidly, and treatment may be significantly more difficult. Most of the diseases caused by agents of bioterrorism are rarely, if ever, seen in modern first-world clinical practice. Physicians are likely to be inexperienced with their clinical presentation and be less aware of alarming symptomatic constellations. Additionally, these agents by definition will have been manipulated in a laboratory and may not present with the classic clinical features of naturally occurring infection. This was dramatically illustrated by some of the inhalational anthrax cases in the United States in October 2001.

Early recognition of bioterrorism is facilitated by the recognition of epidemiologic and clinical clues. Clustering of patients with common signs and symptoms—especially if regionally unusual or otherwise characteristic of bioterrorism agents—is suggestive of an intentional exposure and should prompt expeditious notification of local public health authorities. This approach will also lead to the recognition of outbreaks of naturally occurring disease or emerging pathogens. The recognition of a single case of a rare or nonendemic infection, in the absence of a travel history or other potential natural exposure, should raise the suspicion of bioterrorism. Finally, unusual patterns of disease, such as concurrent illness in human and animal populations should raise suspicions of bioterrorism or another form of emerging infection. An effective response to bioterrorism requires coordination of the medical system at all levels, from the community physician to the tertiary care center, with rapid activation of public health, emergency management, and law enforcement infrastructures.

Threat agents

This section provides a broad overview of the biological threat agents thought to be of major current concern—largely, the CDC category A agents. Extensive coverage of specific pathogens can be found in related chapters in this text and in other sources. These agents can possess rapid person-to-person transmission or the potential for rapid dissemination if weaponized, with high-mortality potential, small infective doses, and significant environmental stability. Data concerning clinical incubation periods, transmission characteristics, and infection-control procedures for agents of bioterrorism are provided in Table 79-3 . Syndromic differential diagnoses for select clinical presentations are detailed in Table 79-4 .

Table 79-3

Infection-Control Issues for Selected Agents of Bioterrorism

Disease	Incubation Period (Days)	Person-to-person Transmission	Infection-Control Practices
Inhalational anthrax	2-43 *	No	Standard
Botulism	12-72 h	No	Standard
Primary pneumonic	1-6	Yes	Droplet
Smallpox	7-17	Yes	Contact and airborne
Tularemia	1-14	No	Standard
Viral hemorrhagic fevers	2-21	Yes	Contact and airborne
Viral encephalitides	2-14	No	Standard
Q fever	2-14	No	Standard
Brucellosis	5-60	No	Standard
Glanders	10-14	No	Standard