Perspective^*

Biologic agents have the potential to cause as many casualties in a densely populated area as a nuclear weapon. If used in a terrorist attack on civilian populations, biologic weapons could also result in widespread social disruption and complete exhaustion of health care resources.^1,5–7

The Centers for Disease Control and Prevention (CDC) classified the major bioterrorist threats into three categories, based on the overall danger to the American public.⁸ Category A agents are the most easily weaponized and disseminated, cause the highest mortality, produce extensive social disruption, and require special public health preparedness systems. Category B agents do not cause as high mortality as category A agents, but they still result in considerable morbidity and require enhancement of current surveillance systems. Category C agents are the third-highest priority and comprise new and emerging agents that are concerning because of their potential to cause significant morbidity. The list of category A, B, and C agents is given in Table 182.1.

Bioterrorism agents are most dangerous to humans when these agents are in aerosolized form.⁶ Particles smaller than 10 mcg effectively reach the alveoli. Certain agents (e.g., anthrax, botulinum) are more resistant to environmental degradation than others (e.g., plague). Some agents (e.g., plague, smallpox) may be transmitted from person to person, thus causing high rates of dissemination and requiring strict isolation measures. Until biologic contaminants are excluded, pulmonary isolation measures should be instituted in all these patients. At present, only anthrax and smallpox have vaccines licensed by the U.S. Food and Drug Administration, and both vaccines require complex administration schedules.⁹

Surveillance and management protocols should be instituted at the hospital level for dealing with large numbers of patients who present with respiratory complaints over a short period of time. If surveillance methods do indicate a bioterrorist attack, the community must work to prevent widespread contamination, to help curb the strain on health care resources. A joint report by the CDC and the U.S. Department of Health and Human Services in February 2007 established guidelines to limit the spread of a pandemic infection.¹⁰ Measures such as the recommendation that ill individuals stay home from work or school, cancellation of large public gatherings, and the use of strict hygiene techniques in the workplace could help avert a health care crisis.

Anthrax^†

Anthrax is caused by Bacillus anthracis, a gram-positive, aerobic, spore-forming bacillus. It is considered to be the biologic agent most likely to be used in a terrorist attack. A bioterrorist attack with powder containing anthrax spores in the United States in 2001 resulted in 22 confirmed cases. The bacteria are simple to obtain and grow. The resulting spores can be aerosolized, are extremely resistant to environmental degradation, and can cause untreated mortality rates up to 50% in exposed individuals. A 1970 World Health Organization study estimated that 50 kg of anthrax spores released in a city with half a million people could cause almost 100,000 deaths.

Anthrax causes cutaneous, gastrointestinal, and pulmonary disease. Human infection, usually cutaneous, typically occurs naturally from exposure to domesticated farm animals, such as sheep and cattle. Cutaneous anthrax is responsible for more than 90% of naturally occurring infections. It initially manifests as an erythematous patch, followed by degeneration into necrotic cellulitis with black eschar similar to a brown recluse spider bite. Gastrointestinal anthrax is extremely rare and causes hemorrhagic gastroenteritis and systemic toxicity.

Smallpox^‡

Variola major virus, a double-stranded DNA virus in the Poxviridae family, causes smallpox. The last confirmed, naturally occurring case of smallpox occurred in 1977. Since then, the existence of variola major virus has been restricted to laboratories in the United States and the former Soviet Union. Because of the extreme contagiousness of the virus, lack of adequate antiviral therapy, and dissolution of the vaccination program, smallpox has extremely high potential to cause considerable morbidity and mortality as a bioterrorism agent. Mortality rates approach 30% in nonimmunized victims.

Classic smallpox infection initially manifests as a nonspecific viral syndrome 2 weeks after exposure, followed by ulcerated lesions in the oropharynx and face. The characteristic vesicular lesions then develop diffusely over the next few days, which when patients are the most contagious. The vesicles eventually transform into pustules and then crust over in the course of 2 weeks. Chickenpox lesions from varicella-zoster virus may be confused with smallpox lesions. Smallpox lesions are characteristically concentrated on the face and extremities (more than the trunk), are in the same stage of development, and usually follow a viral prodrome lasting several days.

Two uncommon variants of smallpox are important to consider because of their high mortality rates. Flat-type smallpox causes soft, macular skin lesions and multiorgan dysfunction, and it has a mortality rate of 95%. Hemorrhagic-type smallpox results in a hyperacute, diffuse bleeding diathesis and is always fatal.

The treatment of smallpox is purely supportive. Postexposure prophylaxis consists of vaccination, which is effective only if it is administered within 4 days of exposure. Vaccinia immunoglobulin may provide some benefit after smallpox exposure and may reduce dermatologic complications after smallpox vaccination. Strict isolation precautions are indicated, including respiratory isolation for confirmed cases and quarantine of exposed individuals.

Plague^§

Plague, the infamous “Black Death” of the Middle Ages, is caused by Yersinia pestis, a gram-negative, facultative anaerobic coccobacillus. Fleas are the main vector, and rodents are the main reservoir. Bubonic plague, an acute febrile form of lymphadenitis, and septicemic plague still occur naturally in parts of Africa, Asia, and the southwestern United States.

A bioterrorist attack from aerosolized droplets would likely cause pneumonic plague, which is highly contagious and impossible to distinguish clinically from severe community-acquired pneumonia. Hemoptysis is more commonly seen in pneumonic plague than in inhalational anthrax. Buboes, the necrotic lymph nodes characteristic of bubonic plague, are notably absent in pneumonic plague.

No findings on complete blood count, chemistry studies, or imaging tests are sufficiently specific for the diagnosis. Chest radiographs are usually abnormal, exhibiting either alveolar infiltrates or pleural effusions. Blood cultures are positive in 90% of cases, and gram-negative coccobacilli with bipolar stain uptake are seen in more than 70% of cases. First-line treatment of pneumonic plague is with streptomycin or gentamicin. Mortality approaches 100% without administration of antibiotics within 24 hours of overt signs of infection.