Epidemiologic principles as applied to bioterrorism

A World Health Organization (WHO) model based on the hypothetical effects engendered by the intentional release of 50 kilograms of aerosolized anthrax spores upwind from a population center of 500,000, a moderate-sized city, estimated that the agent would disseminate in excess of 20 kilometers downwind and that between 84,000 and 210,000 people would be killed or injured by the event, depending on whether the area was in a developed or developing country (WHO, 1970). The complete WHO theoretical analysis showed that casualty estimates depend on the properties of specific pathogens, the environmental setting, and the host population.

Numerous attributes contribute to the selection of a pathogen as a biologic weapon: availability of seed material; ease of cultivation; feasibility of large-scale production; capacity for aerosolization; stability of the product in storage, as a weapon, and in the environment (biologic entities differ in their physical properties); technology for dissemination; cost; and clinical virulence (Artenstein, 2004a). The latter refers to the consistency with which a biological agent causes high mortality, morbidity, and social disruption, and its intrinsic transmission characteristics. The Centers for Disease Control and Prevention (CDC) have prioritized biologic agent threats based on the aforementioned characteristics (CDC, 2000); the major purpose of this classification is to direct and focus public health preparedness strategies (Table 12.3). Category A agents, considered the highest priority, are those associated with high mortality and the greatest potential for major impact on the public health. Additionally, category A agents have been demonstrated to be capable of wide dissemination or person-to-person transmission. Category B agents are moderately high priority concerns. They may be considered "incapacitating" agents because of their potential for moderately high morbidity, but relatively low mortality. Most of the category A and B agents were experimentally weaponized and tested by the former Soviet Union, and are thus of proven feasibility (Alibek, 1999). Category C agents include emerging threats and pathogens that may be available for development into bioweapons in the future. As previously discussed, the potential exploitation of scientific progress by terrorists should prompt innovative thinking as it pertains to risk assessment and public health response. It is critical to be cognizant of future novel threats based upon engineered emergent or re-emergent pathogens (Madsen and Darling, 2006). Towards this end, the current authors have added a miscellaneous grouping of potential threat agents to the extant CDC categories (Table 12.3).

By definition, bioterrorism is insidious; absent of advance warning or specific intelligence information, clinical illness will be manifest before the circumstances of a release event are known. For this reason, health-care providers are likely to be the first responders to this form of terrorism, as symptomatic individuals present for medical attention. This contrasts with the more familiar scenarios in which police, firefighters, paramedics, and other emergency services personnel -traditional first responders - are deployed to the scene of a conventional attack or natural disaster. Physicians and other health-care workers must therefore maintain a high index of suspicion of bioterrorism and recognize suggestive epidemi-ologic clues and clinical features in order to enhance early recognition, optimize the initial management of casualties, and minimize the amplifying effect on the population (Artenstein etal., 2002a).

Early recognition is hampered for multiple reasons. As discussed above, it is likely that the circumstances of any event will only be known in retrospect; therefore it may prove problematic immediately to discern the extent of exposure. Terrorists have an unlimited number of targets in most open, democratic

Table 12.3 Agents of concern for use in bioterrorism

Highest priority (Category A)

Microbe or toxin


Bacillus anthracis


Variola virus


Yersinia pestis


Clostridium botulinum


Fracisella tularensis



Ebola hemorrhagic fevers, Marburg



Lassa fever, South American hemorrhagic



Rift Valley fever, Congo-Crimean

hemorrhagic fevers

Moderately high priority

(Category B)

Coxiella burnetti

Q fever

Brucella spp.


Burkholderia mallei



Viral encephalitides


Ricin intoxication

Staphylococcus aureas enterotoxin B

Staphylococcal toxin illness

Salmonella spp., Shigella dysenteriae,

Food- and water-borne gastroenteritis

Escherichia coli O157:H7, Vibrio

cholerae, Cryptosporidium parvum

Category C


Viral hemorrhagic fevers


Yellow fever

Mycobacterium tuberculosis

Multi-drug resistant tuberculosis


Genetically engineered vaccine- and/or

antimicrobial-resistant category

A or B agents





Hybrid pathogens (e.g. smallpox-plague,


Source: Artenstein (2003), reproduced with permission.

Source: Artenstein (2003), reproduced with permission.

societies; it is unrealistic to expect that, without detailed intelligence data, all of these can be secured at all times. Government institutions, historic landmarks, or large social events may be predictable targets, but there are other, less predictable possibilities. US Department of State data reveal that businesses and other economic interests were the main targets of global terrorism during the period from 1996 to 2001 (US Department of State, 2002). Metropolitan areas are considered vulnerable, but, owing to the expansion of suburbs, commuters, and the clinical latency period between exposure and symptoms inherent with biologic agents, casualties of bioterrorism are likely to present for medical attention in diverse locations and at varying times after common exposures. A covert bioter-rorism attack in New York City on a Wednesday morning may result in clinically ill persons presenting for medical attention over the ensuing weekend to a variety of emergency departments, urgent care centers, and physician offices within a 60-mile (~100-km) commuter radius. Additional cases may be seen hundreds or thousands of miles away at both national and international locations as infected, mobile individuals make use of modern modes of transportation during the clinical incubation period. This adds layers of complexity to an already complicated setting, and illustrates the critical importance of surveillance and real-time communication in this setting.

Further hindering the early recognition of bioterrorism is that the initial symptoms of many of the high priority agents may be non-diagnostic. In the absence of a known exposure, many symptomatic persons may either not seek medical attention early, or if they do they may be misdiagnosed as having a flu-like or other benign illness. Once beyond the early stages many illnesses related to bioterrorism progress rapidly, and treatment may be less successful. Because most of the diseases caused by agents of bioterrorism are rarely (if ever) seen in clinical practice, physicians are likely to be inexperienced with their clinical characteristics; physicians were only able to correctly diagnose diseases due to category A agents 47 percent of the time in one multicenter study (Cosgrove et al., 2005). Additionally, these agents will by definition have been manipulated in a laboratory, and those affected may not present with the classic clinical features seen in naturally occurring infection. This was dramatically illustrated by some of the inhalational anthrax cases in the United States (Jernigan et al., 2001).

Early recognition of bioterrorism is facilitated by the recognition of epidemio-logic and clinical clues. Clustered presentations of patients with common symptoms and signs may suggest a common exposure source, and should prompt expeditious notification of local public health authorities. Aside from capturing the low-probability event of bioterrorism, this approach will also lead to enhanced recognition of outbreaks of naturally occurring disease, or those due to emerging pathogens. The recognition of a single case of a rare or non-endemic infection, in the absence of an appropriate travel history or other potential natural exposure, should raise the suspicion of bioterrorism and should prompt notification of public health authorities. Finally, unusual patterns of disease, such as an acute, fulminant febrile illness in an otherwise healthy young individual, or concurrent illness in human and animal populations, should raise suspicions of bioterrorism or another novel, emerging infection. Since multifocal attacks are expected, attention must be paid to effective, ongoing communication between public health jurisdictions to ensure that a single unusual case is not viewed in a vacuum, as it may not represent an isolated event. An effective response to bioterrorism requires coordination of the medical system at all levels, from the community physician to the tertiary care center, with public health, emergency management, and law enforcement contributions.

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