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Biological Agents as Weapons

By James Madsen, MD, MPH, U.S. Army Medical Research Institute of Chemical Defense

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Biological warfare (BW) is the use of microbiological agents for hostile purposes. Such use is contrary to international law and has rarely taken place during formal warfare in modern history, despite the extensive preparations and stockpiling of biological agents carried out during the 20th century by most major powers (including development of strains resistant to multiple drugs). The area of most concern is the use of BW agents by terrorist groups. BW agents are thought by some to be an ideal weapon for terrorists. These agents may be delivered clandestinely, and they have delayed effects, allowing the user to remain undetected.

The US Centers for Disease Control and Prevention (CDC) has created a priority list of biological agents and toxins (see Table: CDC High-Priority Biological Agents and Toxins). The highest-priority are Category A.

The deliberate use of BW agents to cause mass casualties would probably entail dissemination of aerosols to create disease via inhalation, and thus inhalational anthrax and pneumonic plague are the 2 diseases most likely to occur under these circumstances.

CDC High-Priority Biological Agents and Toxins



A: Highest priority

Bacillus anthracis, causing anthrax

Botulinum toxin from Clostridium botulinum, causing botulism

Yersinia pestis, causing plague

Variola virus, causing variola major (classic smallpox)

Francisella tularensis, causing tularemia

Viral-hemorrhagic-fever (VHF) viruses

  • Arenaviruses, causing Lassa fever and New World VHFs (Machupo, Junin, Guanarito, and Sabia hemorrhagic fevers)

  • Bunyaviridae, causing Crimean Congo hemorrhagic fever and Rift Valley fever

  • Filoviridae, causing Ebola virus disease and Marburg virus disease

  • Flaviviridae, causing yellow fever, Omsk hemorrhagic fever, and Kyasanur Forest disease

B: 2nd highest priority

Brucella species, causing brucellosis

Epsilon toxin of Clostridium perfringens

Salmonella sp, Escherichia coli 0157:H7, and Shigella, causing food poisoning

Burkholderia mallei, causing glanders

Burkholderia pseudomallei, causing melioidosis

Chlamydia psittaci, causing psittacosis

Coxiella burnetii, causing Q fever

Ricin toxin from Ricinus communis

Staphylococcal enterotoxin B

Rickettsia prowazekii, causing typhus fever

Alphaviruses causing viral encephalitides (eg, Venezuelan, eastern, and western equine encephalitides)

Vibrio cholerae, Cryptosporidium parvum, and other agents, causing waterborne diseases

C: 3rd highest priority

Nipah virus, hantavirus, SARS coronavirus, and influenza viruses capable of causing pandemic influenza

Other agents associated with emerging infectious diseases

CDC = US Centers for Disease Control and Prevention; SARS = severe acute respiratory syndrome.


It can be difficult to distinguish use of a BW from a natural outbreak of disease. Clues to the deliberate rather than a natural origin of a disease outbreak include the following:

  • Cases of diseases not usually seen in the geographic area

  • Unusual distribution of cases among segments of the population

  • Significantly different attack rates between those inside and those outside buildings

  • Separate outbreaks in geographically noncontiguous areas

  • Multiple simultaneous or serial outbreaks of different diseases in the same population

  • Unusual routes of exposure (eg, inhalation)

  • Zoonotic disease occurring in humans rather than in animals

  • Zoonotic disease occurring first in humans and then in its typical vector

  • Zoonotic disease arising in an area with a low prevalence of the typical vector for the disease

  • Unusual severity of disease

  • Unusual strains of infectious agents

  • Failure to respond to standard therapy

Epidemiologic investigation of cases and cooperation with law-enforcement resources are crucial, as is risk communication to the general public.

The clinical presentation, diagnosis, and treatment of patients with disease caused by high-risk BW agents are discussed elsewhere in The Manual: Anthrax (see Anthrax), plague (see Plague and Other Yersinia Infections), smallpox (see Smallpox), tularemia (see Tularemia), and viral hemorrhagic fevers (see Arboviruses, Arenaviridae, and Filoviridae). Management of outbreaks due to BW does not differ from that of natural outbreaks except that clinicians must be alert for unusual antibiotic resistance patterns.

Isolation (of patients) and quarantine (of contacts) may be necessary. The most communicable deliberately disseminated diseases are smallpox (for which airborne precautions are necessary) and pneumonic plague (necessitating droplet precautions).


Because of the relatively long incubation periods of diseases caused by BW agents, most lives will be saved or lost in a hospital setting. Adequate supplies of vaccines, antibiotics, and antivirals for hospitalized patients and for contacts are needed, and systems for distributing such medical countermeasures to members of the general public at high risk of exposure are crucial.

The views expressed in this article are those of the author and do not reflect the official policy of the Department of Army, Department of Defense, or the US Government.

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