Biologic Warfare Agent Toxicity


Article Author:
Matthew Smith
Michael Hayoun


Article Editor:
William Gossman


Editors In Chief:
Ron Feller
Grant Goold
Kyle Cohen


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Trevor Nezwek
Radia Jamil
Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
7/11/2019 10:07:23 PM

Introduction

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 as well as increased morbidity and mortality as 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 can only be managed with supportive care. Detection of a biological attack, identification of 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 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 in 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 plague. Plague may be the oldest biological weapon, as it was used by the Mongols 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 consumption of 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 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 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 acute disease. Doxycycline is the treatment of choice. [2]
  • Glanders is caused by Burkholderia mallei. Humans can contract the disease by inhalation or by contact of 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 on 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 not only numerous colleagues and staff but also with public health officials, law enforcement agencies, members of the media, and elected officials. In attacks involving numerous numbers of casualties or high-profile targets such as elected officials, the marshaling of resources to respond will almost certainly reach the national level. (Level V)

Important communication points early in the care of the patient among physicians, nurses, and pharmacists 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 prior to 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 V)


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Biologic Warfare Agent Toxicity - Questions

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How does ricin exert its toxic effect?



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Which of the following antibiotics has been shown to be useful in the treatment of anthrax, plague, tularemia, and brucellosis?



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Which of the following infectious diseases were used in the earliest known form of biological warfare?



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Which of the following regarding the use of anthrax as a biological weapon is not true?



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Biologic Warfare Agent Toxicity - References

References

Toxins as Weapons: A Historical Review., Pita R,Romero A,, Forensic science review, 2014 Jul     [PubMed]
Anthrax: A disease of biowarfare and public health importance., Goel AK,, World journal of clinical cases, 2015 Jan 16     [PubMed]
Pneumonic Plague: The Darker Side of Yersinia pestis., Pechous RD,Sivaraman V,Stasulli NM,Goldman WE,, Trends in microbiology, 2015 Dec 14     [PubMed]
[Yersinia pestis and plague - an update]., Stock I,, Medizinische Monatsschrift fur Pharmazeuten, 2014 Dec     [PubMed]
Plague: history and contemporary analysis., Raoult D,Mouffok N,Bitam I,Piarroux R,Drancourt M,, The Journal of infection, 2013 Jan     [PubMed]
In vitro efficacy of antibiotics commonly used to treat human plague against intracellular Yersinia pestis., Wendte JM,Ponnusamy D,Reiber D,Blair JL,Clinkenbeard KD,, Antimicrobial agents and chemotherapy, 2011 Aug     [PubMed]
Epidemiology of tularemia., Gürcan S,, Balkan medical journal, 2014 Mar     [PubMed]
History of biological warfare and bioterrorism., Barras V,Greub G,, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2014 Jun     [PubMed]
Tularaemia: a challenging zoonosis., Carvalho CL,Lopes de Carvalho I,Zé-Zé L,Núncio MS,Duarte EL,, Comparative immunology, microbiology and infectious diseases, 2014 Mar     [PubMed]
Armies of pestilence: CNS infections as potential weapons of mass destruction., Hart BL,Ketai L,, AJNR. American journal of neuroradiology, 2015 Jun     [PubMed]
Rodents as potential couriers for bioterrorism agents., Lõhmus M,Janse I,van de Goot F,van Rotterdam BJ,, Biosecurity and bioterrorism : biodefense strategy, practice, and science, 2013 Sep     [PubMed]
Bartonella and Brucella--weapons and strategies for stealth attack., Ben-Tekaya H,Gorvel JP,Dehio C,, Cold Spring Harbor perspectives in medicine, 2013 Aug 1     [PubMed]
Bioterrorism: pathogens as weapons., Anderson PD,Bokor G,, Journal of pharmacy practice, 2012 Oct     [PubMed]
[Today's threat of ricin toxin]., From S,Płusa T,, Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego, 2015 Sep     [PubMed]
Poxvirus countermeasures during an emergency in the United States., Bice S,Yeskey K,, Disaster medicine and public health preparedness, 2015 Apr     [PubMed]
Management of potential bioterrorism-related conditions., Friedlander AM,, The New England journal of medicine, 2015 Jun 4     [PubMed]
Laboratory-acquired human glanders--Maryland, May 2000.,, MMWR. Morbidity and mortality weekly report, 2000 Jun 23     [PubMed]
Erenler AK,Güzel M,Baydin A, How Prepared Are We for Possible Bioterrorist Attacks: An Approach from Emergency Medicine Perspective. TheScientificWorldJournal. 2018     [PubMed]
Christian MD, Biowarfare and bioterrorism. Critical care clinics. 2013 Jul     [PubMed]

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