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Am Fam Physician. 2021;104(4):376-385

This clinical content conforms to AAFP criteria for CME.

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Bioterrorism is the deliberate release of viruses, bacteria, toxins, or fungi with the goal of causing panic, mass casualties, or severe economic disruption. From 1981 to 2018, there were 37 bioterrorist attacks worldwide. The Centers for Disease Control and Prevention (CDC) lists anthrax, botulism, plague, smallpox, tularemia, and viral hemorrhagic fevers as category A agents that are the greatest risk to national security. An emerging infectious disease (e.g., novel respiratory virus) may also be used as a biological agent. Clinicians may be the first to recognize a bioterrorism-related illness by noting an unusual presentation, location, timing, or severity of disease. Public health authorities should be notified when a biological agent is recognized or suspected. Treatment includes proper isolation and administration of antimicrobial or antitoxin agents in consultation with regional medical authorities and the CDC. Vaccinations for biological agents are not routinely administered except for smallpox, anthrax, and Ebola disease for people at high risk of exposure. The American Academy of Family Physicians, the CDC, and other organizations provide bioterrorism training and response resources for clinicians and communities. Clinicians should be aware of bioterrorism resources.

Bioterrorism is the deliberate release of viruses, bacteria, toxins, or fungi with the goal of causing panic, mass casualties, or economic disruption.1 Historical records indicate that biological warfare has occurred throughout history, as long ago as the 14th century B.C.2

Although many pathogens may be used in a bioterrorist attack, the most concerning agents to national security and public health are anthrax, smallpox, plague, tularemia, botulism, and viral hemorrhagic fevers, in descending order of likelihood1 (Table 13). These pathogens are considered category A agents by the Centers for Disease Control and Prevention (CDC) and are the focus of this article.

A: most concerning to national security and public health because of ease of dispersal, transmission between people, high mortality rates, and the potential to cause panic; significant planning needed for public health preparednessAnthrax: Bacillus anthracis
Plague: Yersinia pestis
Tularemia: Francisella tularensis
Smallpox: variola major
Viral hemorrhagic fevers: Ebola, Lassa, Machupo, Marburg
Botulism: Clostridium botulinum
B: lower mortality rates compared with category A agents; relative ease of dissemination and moderate morbidity; requires special resources for surveillance and diagnosticsBrucellosis: Brucella species
Escherichia coli O157:H7*
Glanders: Burkholderia mallei
Melioidosis: Burkholderia pseudomallei
Psittacosis: Chlamydia psittaci
Q fever: Coxiella burnetii
Typhus fever: Rickettsia prowazekii
Vibrio cholerae
Cryptosporidium parvum
Viral encephalitis:
 Eastern equine encephalitis
 Venezuelan equine encephalitis
 Western equine encephalitis
Epsilon: Clostridium perfringens
Ricin toxin (castor beans)
Staphylococcal enterotoxin B
C: includes any emerging pathogen that could be exploitedAny emerging pathogenAny emerging pathogenAny emerging pathogen

Although bioterrorism is currently considered a low-probability event, many pathogens that could be used in bioterrorist attacks occur naturally. Five of the category A agents—anthrax, botulism, plague, Ebola virus, and Lassa fever—were noted to occur naturally in endemic regions in 2020.4 There is also concern that these (or other) pathogens could be altered to increase virulence or cause resistance to current medications and vaccines.5 Laboratory accidents have resulted in the release of harmful pathogens, and the shipment of viable agents and unaccounted stocks of these agents highlight the risk of poor biosecurity.2,6,7 An emerging infectious disease, such as a novel respiratory virus, might also be exploited, bypassing the expertise needed to obtain and weaponize other well-known agents.

In 1975, all but 12 nations participated in the Biological Weapons Convention, which prohibited the development, production, acquisition, use, and stockpiling of biological agents.8 Despite this, from 1981 to 2018, there were 37 bioterrorist attacks worldwide.9

In 2001, powdered anthrax spores were mailed through the United States Postal Service to several government employees and news media outlets. This attack resulted in 11 cutaneous and 11 inhalational cases of anthrax, with five of the inhalational cases being fatal.1,10 An estimated $320 million was needed for decontamination, and 10,000 people were recommended for postexposure prophylaxis.11,12 In 2020, ricin (a poison found in castor beans) was mailed to the President of the United States and five residents of Texas.13 Ricin can cause death within 36 to 72 hours, and there is no known antidote.14

The initial diagnosis of illness caused by biological agents could be delayed because of a lack of clinical experience with or knowledge about these agents.15 The goal of this article is to provide primary care physicians with basic information about category A agents, supporting them in detecting and responding to a bioterrorist attack, which may include assisting in a mass casualty event.15,16 Primary care physicians may be the first to recognize a bioterrorism-related illness by noting an unusual presentation, location, timing, or severity of disease.


Anthrax is a naturally occurring zoonotic disease with worldwide distribution caused by the spore-forming, gram-positive, rod-shaped bacterium, Bacillus anthracis.17 Although anthrax is a disease primarily affecting wild and domestic herbivores, it occasionally causes human illness and is potentially fatal.

The human disease has a variety of manifestations. Cutaneous disease is most common, but anthrax that is inhaled possesses a higher degree of lethality.18 The inhalational form is of concern to bioterrorism because it is easily disseminated and can cause widespread illness and death.2,19 For instance, an aerosolized release of anthrax into the Washington, DC area could result in 1 million to 3 million deaths.16

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