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Biologic Warfare Agent Toxicity

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Last Update: July 1, 2022.

Continuing Education Activity

Biological warfare agents include bacteria, viruses, fungi, and biological toxins. Some agents are frequently lethal, while others are intended to cause illness or incapacitation. Biological warfare can be directed not only at the human population but also at crops and livestock. Biological warfare agents are most likely to be dispersed as aerosols to be more easily spread amongst large populations. However, certain agents can be spread from person to person or by vectors, ingestion, direct contact, or other methods. This activity reviews the most common biologic agents addressing the evaluation and treatment of these conditions.


  • Identify agents that may be used in biological warfare.
  • Summarize the pathophysiology and accompanying presentation of patients affected by various biological warfare agents.
  • Review the treatment regimens for different biological warfare agents.
  • Explain the importance of collaboration and communication among the interprofessional team, including first responders, public health officials, and the medical team, to ensure appropriate precautionary measures and incident management are taken.
Access free multiple choice questions on this topic.


Biological warfare agents include bacteria, viruses, fungi, and biological toxins. Some agents are frequently lethal, while others are intended to cause illness or incapacitation. Biological warfare can be directed not only at the human population but also at crops and livestock. More than 180 pathogens have been researched or employed as biological weapons, including anthrax, tularemia, brucellosis, plague, Legionnaire’s disease, Q fever, glanders, melioidosis, smallpox, viral hemorrhagic fevers, influenza, ricin, botulinum toxin, staphylococcal enterotoxin B, coccidiosis, rice blast, and wheat rust. Biological warfare agents are most likely to be dispersed as aerosols to be more easily spread amongst large populations. However, certain agents can be spread from person to person or by vectors, ingestion, direct contact, or other methods.

Issues of Concern

In the absence of a declared or witnessed biological attack, early symptoms of biological warfare agents are likely to be nonspecific. Clues to a biological warfare attack include unusually large numbers of patients presenting simultaneously with similar symptoms and increased morbidity and mortality compared to more common illnesses. Other epidemiologic red flags might include significant numbers of patients who live or work in the same area, attended the same event, ate at the same restaurant, etc. Depending on the biological warfare agent involved, person-to-person transmission may or may not be a concern. The use of agents that are capable of causing severe illness and death may quickly cause healthcare resources to be overwhelmed with patients requiring critical care and life-saving interventions, in addition to what may be a large number of asymptomatic or mildly symptomatic patients who seek medical care. Certain agents can be treated with medications or even avoided with post-exposure immunizations or prophylactic medications, whereas others are only manageable with supportive care. Detection of a biological attack, identifying the agents used, and determining the population at risk are vital to both incident management and patient management.[1][2][3][4][5][6][7]

Clinical Significance

Anthrax has clinical relevance as a potential cause of infection either environmentally or as a weaponized agent. Anthrax is caused by Bacillus anthracis and presents in three clinical forms: ingestion, cutaneous, or inhalation. As few as 2500 spores may cause infection; infection is not spread from person to person. Inhalational anthrax is the most lethal form and presents clinically with four to ten days of flu-like symptoms followed by rapid deterioration; hemorrhagic mediastinitis may be seen as a widened mediastinum on chest radiography. Cutaneous anthrax causes a characteristic black eschar. Strains of weaponized anthrax may be penicillin-resistant. Thus the treatments of choice for patients of all ages are doxycycline and ciprofloxacin.[8]

Plague is caused by Yersinia pestis and presents three clinical variants of the disease: septicemic, pneumonic, and bubonic. Pneumonic plague is 100% fatal if untreated. Plague is usually transmitted from rodent reservoirs to humans by the bite of flea vectors. However, the pneumonic form of plague can spread from person to person. In humans, the disease proliferates in lymph nodes, and the buboes of bubonic plague are the resultant extremely tender lymphadenopathy. Streptomycin, ciprofloxacin, doxycycline, and chloramphenicol can effectively treat the plague. Plague may be the oldest biological weapon, as the Mongols used it against Caffa in 1347.[9][10][11][12]

Brucellosis is caused by Brucella species. It is easily aerosolized, and few organisms are required to cause disease. Person-to-person transmission is rare; it is usually transmitted to humans from infected animals either by contact or by consuming undercooked meat or unpasteurized dairy products. Symptoms include a headache, fever, arthralgia, back pain, hepatomegaly, transaminitis, orchitis, epididymitis, endocarditis, and anemia. Death occurs in 2% of cases, and endocarditis is the most common cause of death. Brucellosis is treated with doxycycline plus either rifampin or streptomycin; sulfamethoxazole/trimethoprim may be used instead of doxycycline in children.[13]

Tularemia is caused by Francisella tularensis and has six clinical variants: ulceroglandular, oculoglandular, glandular, oropharyngeal, pneumonic, and typhoidal. The ulceroglandular form is most common. It can be spread by arthropod vectors but is not spread from person to person. It is easily aerosolized, highly infectious, and highly incapacitating, although death occurs in less than 1% with treatment. Streptomycin is the treatment of choice; gentamicin, doxycycline, and ciprofloxacin may also be used.[14][15]

Q Fever is caused by Coxiella burnetii. It can be spread by ingestion or aerosolization as well as by tick vectors. It is easy to aerosolize, and fewer than ten organisms can cause infection. Symptoms include fever, chills, malaise, sweating, arthralgia, myalgia, cough, pleurisy, nausea, vomiting, and diarrhea. However, roughly half of the people infected will be asymptomatic. It is considered an incapacitating agent. However, it can cause pneumonia and endocarditis, which may be lethal. A small percentage of cases may become chronic. However, the chronic form of the disease causes more deaths than an acute disease. Doxycycline is the treatment of choice.[2]

Burkholderia mallei cause glanders. Humans can contract the disease by inhalation or contact with the organism with mucosal surfaces or breaks in the skin. Infections may be localized but often become disseminated. Symptoms include fever, chills, night sweats, lymphadenopathy, headache, myalgias, tachypnea, nausea, vomiting, and diarrhea. Glanders is highly lethal without treatment. The recommended treatment is doxycycline, trimethoprim/sulfamethoxazole, and chloramphenicol.[16]

Smallpox is caused by the Variola virus. The four clinical presentations of smallpox disease are ordinary, modified, malignant, and hemorrhagic. It is spread by airborne droplets and contact with body fluids. Ordinary smallpox begins as a macular rash that progresses to pustules and then to vesicles; lesions first present on the face and distal extremities and spread to the trunk. Unlike chickenpox, lesions in all parts of the body progress through the clinical stages at the same time. Overall mortality is approximately 30%. Cidofovir has been theorized as a treatment of and short-term prophylaxis against smallpox. Smallpox vaccination within 72 hours of exposure can prevent the disease; vaccination within three to seven days of exposure will not prevent disease but will limit symptoms.[17]

Ricin is a naturally occurring protein produced in the seeds of the castor oil plant. It inactivates ribosomes, which results in toxicity because of the inhibition of protein synthesis. The median lethal dose by inhalation in humans is five to ten micrograms per kilogram. Symptoms include nausea, diarrhea, tachycardia, hypotension, and seizures. Treatment is supportive, and no antidote exists.[18][19]

Botulinum toxin is produced by the bacterium Clostridium botulinum. The toxin causes symmetrical descending flaccid paralysis by preventing the release of acetylcholine at the neuromuscular junction. As little as one to two nanograms per kilogram can be lethal to humans if given intravenously. Treatment includes antitoxin and respiratory support; prolonged mechanical ventilation may be necessary.[18]

Enhancing Healthcare Team Outcomes

The relatively recent use of biological agents such as ricin and anthrax demonstrates how even small-scale biological warfare attacks will quickly become international news. Once a patient has been diagnosed with a disease caused by a biological warfare agent, healthcare providers will be responsible for communicating with numerous colleagues and staff and public health officials, law enforcement agencies, members of the media, and elected officials. In attacks involving numerous casualties or high-profile targets such as elected officials, the marshaling of resources to respond will almost certainly reach the national level.

Important communication points early in patient care among the interprofessional healthcare team, including clinicians, nurses, pharmacists, and public health officials, will include adequate decontamination of the patient and appropriate precautions for first responders and hospital staff to avoid the spread of contagious diseases or additional casualties. Training and education before such an event will be more effective than just-in-time training after an event has occurred when emotions run high and resources may run low. In large-scale events, it will be essential for healthcare staff to have a clear understanding of their available resources as well as the anticipated demands on those resources, and continuously communicating with government officials to access medical supply stockpiles and resources for the capacity to treat large numbers of patients will be vital. [Level 5]

Review Questions


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Lõhmus M, Janse I, van de Goot F, van Rotterdam BJ. Rodents as potential couriers for bioterrorism agents. Biosecur Bioterror. 2013 Sep;11 Suppl 1:S247-57. [PubMed: 23971813]
Hart BL, Ketai L. Armies of pestilence: CNS infections as potential weapons of mass destruction. AJNR Am J Neuroradiol. 2015 Jun;36(6):1018-25. [PMC free article: PMC8013034] [PubMed: 25477355]
Anderson PD, Bokor G. Bioterrorism: pathogens as weapons. J Pharm Pract. 2012 Oct;25(5):521-9. [PubMed: 23011963]
Friedlander AM. Management of potential bioterrorism-related conditions. N Engl J Med. 2015 Jun 04;372(23):2272. [PubMed: 26039617]
Erenler AK, Güzel M, Baydin A. How Prepared Are We for Possible Bioterrorist Attacks: An Approach from Emergency Medicine Perspective. ScientificWorldJournal. 2018;2018:7849863. [PMC free article: PMC6076891] [PubMed: 30104916]
Christian MD. Biowarfare and bioterrorism. Crit Care Clin. 2013 Jul;29(3):717-56. [PMC free article: PMC7127345] [PubMed: 23830660]
Goel AK. Anthrax: A disease of biowarfare and public health importance. World J Clin Cases. 2015 Jan 16;3(1):20-33. [PMC free article: PMC4295216] [PubMed: 25610847]
Pechous RD, Sivaraman V, Stasulli NM, Goldman WE. Pneumonic Plague: The Darker Side of Yersinia pestis. Trends Microbiol. 2016 Mar;24(3):190-197. [PubMed: 26698952]
Stock I. [Yersinia pestis and plague - an update]. Med Monatsschr Pharm. 2014 Dec;37(12):441-8; quiz 449. [PubMed: 25643450]
Raoult D, Mouffok N, Bitam I, Piarroux R, Drancourt M. Plague: history and contemporary analysis. J Infect. 2013 Jan;66(1):18-26. [PubMed: 23041039]
Wendte JM, Ponnusamy D, Reiber D, Blair JL, Clinkenbeard KD. In vitro efficacy of antibiotics commonly used to treat human plague against intracellular Yersinia pestis. Antimicrob Agents Chemother. 2011 Aug;55(8):3752-7. [PMC free article: PMC3147644] [PubMed: 21628541]
Ben-Tekaya H, Gorvel JP, Dehio C. Bartonella and Brucella--weapons and strategies for stealth attack. Cold Spring Harb Perspect Med. 2013 Aug 01;3(8) [PMC free article: PMC3721268] [PubMed: 23906880]
Gürcan S. Epidemiology of tularemia. Balkan Med J. 2014 Mar;31(1):3-10. [PMC free article: PMC4115998] [PubMed: 25207161]
Carvalho CL, Lopes de Carvalho I, Zé-Zé L, Núncio MS, Duarte EL. Tularaemia: a challenging zoonosis. Comp Immunol Microbiol Infect Dis. 2014 Mar;37(2):85-96. [PMC free article: PMC7124367] [PubMed: 24480622]
Centers for Disease Control and Prevention (CDC). Laboratory-acquired human glanders--Maryland, May 2000. MMWR Morb Mortal Wkly Rep. 2000 Jun 23;49(24):532-5. [PubMed: 10923853]
Bice S, Yeskey K. Poxvirus countermeasures during an emergency in the United States. Disaster Med Public Health Prep. 2015 Apr;9(2):121-6. [PubMed: 26060872]
Pita R, Romero A. Toxins as Weapons: A Historical Review. Forensic Sci Rev. 2014 Jul;26(2):85-96. [PubMed: 26227025]
From S, Płusa T. [Today's threat of ricin toxin]. Pol Merkur Lekarski. 2015 Sep;39(231):162-4. [PubMed: 26449579]
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