1. 
   

   What epidemiologic clues should heighten suspicion of a bioterrorism attack?

   
   
2. 
   

   What is the appropriate organizational response to a suspected bioterrorism event?

   
   
3. 
   

   What clinical syndromes are associated with possible agents of bioterrorism?

Epidemiologic Features Suggestive of Bioterrorism

Several disease entities should raise the suspicion that a bioterrorist attack is occurring, especially when clusters of similar cases are seen. These include:

• A life-threatening, apparently infectious illness in a young, otherwise healthy person, not due to toxic shock syndrome, meningococcus, or Rocky Mountain spotted fever
  
• A serious pneumonia in a young, otherwise healthy adult
  
• Influenza outbreaks occurring during the offseason
  
• A febrile illness with a widened mediastinum on chest radiography (as seen in inhalation anthrax)
  
• The characteristic vesicular rash of smallpox
  
• The capillary leak syndrome of viral hemorrhagic fevers
  
• Laboratory suspicion or diagnosis of infections due to glanders (Burkholderia mallei), anthrax, smallpox, hemorrhagic fevers
  
• Plague (Yersinia pestis) or tularemia (Francisella tularensis) outside of endemic areas
  
• Neurologic findings compatible with botulism

After a proven or suspected bioterrorist attack, a tremendous surge of patients may affect, and potentially overwhelm, many areas of the hospital, including the emergency department, microbiology laboratory, outpatient clinics, and inpatient medical wards. This may include many persons seeking medical evaluation who are unaffected by the bioterrorist agent. It may be problematic to differentiate the “worried well” from patients in the early stages of infection due to a bioterrorist agent. For example, anthrax (and many other infections) may first present as a “flu-like illness.” If there is a recognized bioterrorism event due to the intentional release of B. anthracis spores during a busy influenza season, many people who would otherwise remain at home with influenza are likely to seek medical attention out of fear of inhalation of anthrax.

A bioterrorism event requires an organized, prompt response to mobilize all available resources. Hospitals should have an approved infectious disease emergency management and response plan (as in Figure 266-1) in place for potential bioterrorism agents, as well as for other highly virulent infections, including SARS and pandemic influenza. If the hospital does not have such a plan in place, hospitalists should contact specific services:

• Infection control/hospital epidemiology, to ensure that patients are placed on the proper precautions to prevent nosocomial transmission of infection. These vary with the suspected agent. For some, such as anthrax and botulism, there is no risk of person-to-person transmission. For others, such as plague pneumonia and smallpox, the risk is substantial.
  
• Public health authorities, to report possible cases (usually done by infection control/hospital epidemiology), and to engage their clinical expertise and laboratory resources.
  
• The clinical microbiology laboratory, to ensure that appropriate specimens are properly collected and transported, and to ensure that the dangers to laboratory workers are minimized. Bioterrorism agents such as Francisella tularensis, Brucella species, and viruses (including smallpox, SARS, and viral hemorrhagic fevers) are each associated with a major risk of laboratory-acquired infection.
  
• The anatomic pathology department, in the event that tissue or fluid from a patient is sent for diagnostic purposes. As with microbiology, direct communication with pathology can help optimize diagnostic testing and ensure that proper handling and safety measures are used. This may also assist in contingency planning, such as establishment of a temporary morgue.
  
• The medical examiner should be alerted in the event of patient deaths, as these may be investigated as criminal acts.
  
• The infectious disease service is essential in the diagnosis and management of the victims of bioterrorism.
  
• Hospital administration, to coordinate internal responses and deal with the flow of information both inside and outside the hospital, including dealing with news media.
  
• The inpatient pharmacy, to locate specific treatments for hospitalized patients and to maximize supplies for additional patients who may present to the hospital (this may require activation of the National Antibiotic Stockpile by federal authorities).
  
• The critical care service, since affected patients may need ICU admission. Mechanical ventilation may be necessary for pneumonia (as in plague and tularemia), acute respiratory distress syndrome (as in ricin poisoning), and neuromuscular disease (as in botulism).
  
• Other clinical services may include dermatology for evaluation and possible skin biopsy for suspected cases of smallpox and cutaneous anthrax, ophthalmology for oculoglandular tularemia, and neurology for suspected botulism.

The bioterrorism agents of greatest concern are classified by the U.S. Centers for Disease Control and Prevention (CDC) as “Category A” agents, so designated because they are easily disseminated or transmitted from person to person and have high mortality rates. These include Bacillus anthracis (anthrax), Clostridium botulinum (botulism), Francisella tularensis (tularemia), Yersinia pestis (plague), smallpox, and viral hemorrhagic fevers.

Anthrax

Bioweapon Potential

Anthrax is a zoonotic infection of large herbivores, maintained in nature by spores that are viable in the environment for decades. Bacillus anthracis infections have a high morbidity and mortality due mainly to their production of two toxins, edema factor and lethal factor, which lead to tissue necrosis and hypotension. Cultures of B anthracis may be weaponized by drying, milling into fine particles, and adding an agent to counter electrostatic clumping and allow airborne dispersal. Anthrax is a proven bioweapon. Accidental release of spores from a bioweapons facility in Sverdlosk, Russia in 1979 caused at least 66 deaths. The 2001 U.S. outbreak from contaminated mail led to 22 cases, including five deaths.

Clinical Features

Inhalational anthrax is the form most likely to result from a bioterror attack. The incubation period is usually from one to seven days, but may be longer; the exact incubation period in any given case may be difficult to ascertain, as spores may settle on surfaces and become airborne again when the environment is disturbed. After initial “flu-like” symptoms, patients develop high fever, respiratory distress, and shock within one to five days. Chest radiography may reveal pulmonary infiltrates and pleural effusions; widening of the mediastinum from hemorrhagic mediastinitis is a frequent and characteristic finding. The death rate of inhalation anthrax in the 2001 U.S. attack was 45%, lower than the historical mortality of 85%.

Cutaneous anthrax is the most common form of naturally-acquired anthrax, and comprised about half of cases in the 2001 attack. It begins as a pruritic papule, and evolves into a hemorrhagic vesicle. Tissue necrosis results in the formation of a black eschar within 7–10 days (Figure 266-2). The eschar is usually painless, and is surrounded by impressive nonpitting edema. Without antibiotics, 20% will die of systemic infection. In the rest, the eschar eventually sloughs off, with symptom resolution in two to six weeks.

Two other forms of anthrax are unlikely to be seen in the context of a bioterrorism event. Gastrointestinal anthrax

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