Unless otherwise noted, all information presented in this article is derived from Inglesby TV, Dennis DT, Henderson DA, et al., for the Working Group on Civilian Biodefense. Plague as a biological weapon: medical and public health management. JAMA. 2000;283(17):2281-2290.
Plague is an infectious disease caused by Yersinia pestis, a naturally occurring bacterium found primarily in wild rodents. Plague has been the cause of 3 of the great pandemics of the modern era—in the mid-6th century, the mid-14th century (known as the Black Death), and the early 20th century.
Three forms of naturally occurring plague infection exist:
Plague is recognized by public health experts as a re-emerging infectious disease. Worldwide incidence has reached approximately 2,000 to 3,000 reported cases each year. For example, according to the WHO fact sheet on plague, the worldwide reported incidence in 2003 was 2,118 cases with 182 deaths. The disease is endemic in rodent populations in much of Southern Asia, parts of Africa, and the Americas. According to the CDC, approximately 5 to 15 naturally occurring human cases of plague are reported in the United States each year, usually in rural areas of the Southwest (eg, New Mexico, California, Colorado, and Texas). Advances in living conditions, public health, and antibiotic therapy make future natural plague pandemics improbable, but plague outbreaks following an attack with a biological weapon do pose a serious risk.
Plague is currently considered to be one of the most serious bioterrorism threats. Y. pestis was developed as an aerosol weapon by several countries in the past. Aerosol dissemination of bacteria would cause primary pneumonic plague in the exposed population, an otherwise uncommon, highly lethal, and contagious form of plague.
A number of factors contribute to concern over the use of plague as a biological weapon:
There is widespread availability of Y. pestis in microbe banks around the world.
There is widespread natural availability of the Y. pestis bacteria in endemic areas
Reports indicate that techniques for mass production and aerosol dissemination of Y. pestis have been developed.
The fatality rate of pneumonic plague in untreated cases is extremely high.
Plague has the potential for secondary spread from person to person following an attack.
Y. pestis can be disseminated in aerosol form.
Plague has a low infectious dose.
Antibiotic resistant strains of Y. pestis exist in nature.
A 1970 World Health Organization (WHO) assessment asserted that in a worst-case scenario a dissemination of 50 kg of Y. pestis in an aerosol cloud over a city of 5 million might result in 150,000 cases of pneumonic plague. Of those, 80,000 to 100,000 cases would require hospitalization, and 36,000 victims would be expected to die. (See “The History of Bioterrorism: Plague,” a short video from the CDC.)
Diagnosis of plague is based on clinical presentation of symptoms and confirmed by laboratory testing, which usually takes 24 to 48 hours. There are no widely available rapid diagnostic tests for plague. The first sign of a bioterrorist attack with plague would most likely be a sudden surge of patients presenting at hospitals and doctors’ offices with symptoms of severe pneumonia and sepsis.
Clinical Presentation of Plague
|Plague Infection||Incubation Period||Signs and Symptoms||Lethality|
|Pneumonic||2 to 4 days (range 1 to 6 days) after exposure||The first signs are fever, cough, muscle aches, and headache, with progression to chest pain, difficulty breathing, and hemoptysis (coughing blood). Nausea, vomiting, and abdominal pain might also occur.||Pneumonic plague is highly lethal when untreated or when antibiotic treatment is started more than 24 hours after the onset of symptoms. Untreated, the fatality rate of pneumonic plague approaches 100%.|
|Bubonic||1 to 8 days following exposure to an infected animal or sustaining a flea bite||Sudden onset of fever, chills, weakness, headache, and buboes will occur, typically followed by nausea and vomiting. The bubo is an extremely painful bump resulting from a swollen, tender lymph node, usually in the groin, armpit, or neck.||Without prompt treatment, or if left untreated, bubonic plague has a fatality rate of 50% to 60%.|
|Septicemic||Untreated, bubonic or pneumonic plague may develop into septicemic infection 2 to 6 days after initial symptoms appear.||Fever, chills, abdominal pain, nausea, vomiting, diarrhea. Later, this infection may lead to coagulation problems and gangrene of the extremities.||Without prompt treatment, or if left untreated, the fatality rate of septicemic plague approaches 100%.|
A: Cervical bubo in patient with bubonic plague.
|X-ray of a patient with pneumonic plague infection involving both lungs. Source: CDC Public Health Image Library (ID #4136).|
|Xenopsylla cheopis (oriental rat flea) engorged with blood. Source: CDC Public Health Image Library (ID #2025).|
Fleas are natural vectors (carriers) of Y. pestis, and the bacteria are typically transmitted to and among rodents via flea bite. Humans may contract plague through a flea bite or by handling an infected animal or breathing in an aerosolized form of the bacteria.
Neither bubonic or septicemic plague are known to spread directly from person to person. However, pneumonic plague does spread from person to person through respiratory droplets over short distances.
The Centers for Disease Control and Prevention (CDC) recommends that individuals suspected of having pneumonic plague be placed in isolation, with respiratory droplet precautions, and monitored for symptoms for the first 48 hours of antibiotic treatment. Those with confirmed pneumonic plague should remain in isolation under droplet precautions until all laboratory cultures are negative, indicating that disease has run its course. Standard respiratory droplet precautions should also be taken by individuals in close contact with patients with confirmed or suspected pneumonic plague. Contacts of patients with plague should be identified for surveillance purposes, and any contacts who develop plague should be placed in isolation.
Early antibiotic therapy is recommended for persons deemed exposed to or infected with plague. Tetracyclines (eg, doxycycline), fluoroquinolones (eg, ciprofloxacin), and aminoglycosides (eg, streptomycin, although not widely available, and gentamicin) are all antibiotics that have been used for post-exposure prophylaxis and treatment of plague. Specific treatment recommendations following a biological attack with plague will depend on several factors, including antibiotic susceptibility of the strain.
Antibiotic treatment should be initiated within 24 hours for patients showing symptoms of pneumonic infection, and should be continued for 10 days. Prophylactic antibiotics may be administered to protect people who have had known direct contact with infected patients, and should be continued for 7 days. People with suspected exposure to pneumonic plague should be placed under surveillance and monitored for symptoms. If symptoms develop, antibiotic therapy should be initiated immediately and continued for 10 days. In addition to antibiotic prophylaxis, people with established ongoing exposure to a patient with pneumonic plague should use standard respiratory droplet precautions.
A vaccine for plague is not currently available for civilian use in the United States. A U.S. licensed vaccine exists, but it is no longer commercially available. This vaccine has some efficacy in preventing or lessening the severity of bubonic disease in a pre-exposure setting; however, it has not been shown to be effective in preventing pneumonic plague.
Research and development efforts for both an attenuated live vaccine and a subunit vaccine that protects against pneumonic plague are ongoing.
Additionally, a number of promising new antibiotics and intervention strategies have yet to be fully explored experimentally.
Borio L. Plague as an agent of bioterrorism. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases, 6th Edition. Philadelphia, PA: Churchill Livingstone; 2005.
CDC Plague Web page. Centers for Disease Control and Prevention. http://www.cdc.gov/ncidod/dvbid/plague. Accessed February 25, 2014.
Health aspects of chemical and biological weapons, 1st edition. World Health Organization, United Nations; 1970. http://www.who.int/csr/delibepidemics/biochem1stenglish/en/index.html. Accessed February 25, 2014.
Human plague––four states. MMWR. August 25, 2006;55 (Dispatch): 1-3. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm55d825a1.htm. Accessed February 25, 2014.
Inglesby TV, Dennis DT, Henderson DA, et al., for the Working Group on Civilian Biodefense. Plague as a biological weapon: medical and public health management. JAMA. 2000;283(17):2281-2290. http://jama.ama-assn.org/content/283/17/2281.full. Accessed February 25, 2014.
Plague overview. National Institute of Allergy and Infectious Disease, National Institutes of Health. http://www3.niaid.nih.gov/healthscience/healthtopics/plague. Accessed February 25, 2014.
Visual Dx: Visual clinical decision support software. http://www.logicalimages.com/resourcesBTAgents.htm. Accessed February 25, 2014.