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NORD is very grateful to the Centers for Disease Control and Prevention, Division of Vector-Borne Infectious Diseases, for assistance in the preparation of this report.

Synonyms of Plague

Disorder Subdivisions

General Discussion

Plague is an acute, severe infectious disease caused by the bacterium Yersinia pestis. The bacterium is found in fleas and wild rodents such as rats, squirrels, chipmunks or prairie dogs. Plague is a zoonotic disease, which means it can be transmitted to humans through animals, most often through the bites of fleas or through direct contact with infected animal tissue. The disease is most common in parts of Africa and Asia but it also occurs in some areas of the western United States. Symptoms can include an abrupt onset of chills, fever, and enlarged, painful lymph nodes (buboes). Treatment must start immediately to avoid life-threatening complications. Although plague is extremely rare in the United States, interest in the infection has heightened in recent years because of its potential use as an agent of biological warfare.


The symptoms of plague vary greatly depending upon the specific form that develops. The main clinical forms of plague are: bubonic, pneumonic, and septicemic.

Bubonic Plague
Bubonic plague is the most common form of the disease. Symptoms usually develop 2-6 days after exposure to the bacterium and include the sudden onset of fever, chills, weakness, headaches, muscle pain and a general feeling of discomfort or ill health (malaise). An infected individual develops buboes - tender, inflamed swelling of lymph nodes. Buboes are firm and often very painful. The lymph nodes of the groin, armpit (axilla) or neck are most often involved. Some individuals may experience gastrointestinal symptoms including nausea, vomiting, diarrhea and abdominal pain.

If untreated, the bacteria can spread from the affected lymph nodes to the bloodstream (septicemia) and the lungs (pneumonia) and cause toxicity, shock, and other life-threatening complications.

Pneumonic Plague
Pneumonic plague is infection of the lungs by the Yersinia pestis bacterium. It can occur as a complication of bubonic plague in which the bacteria spread to the lungs through the bloodstream, or as a primary infection in which the bacterium is inhaled directly into the lungs.

Affected individuals can develop a wide variety of symptoms including fever, chills, a rapid heartbeat, cough, chest pain, severe headaches and the coughing up of bloody sputum (hemoptysis). Gastrointestinal symptoms such as nausea, vomiting, diarrhea, and abdominal pain may also occur. If untreated, this form of plague can rapidly progress to multiple organ failure, adult respiratory distress syndrome and ultimately death.

Septicemic Plague
This form of plague is characterized by massive growth of bacteria in the blood. It can occur as bacteria in the lymph nodes (bubonic plague) spread to the bloodstream, or as a primary infection (no swollen lymph nodes). Affected individuals may develop prominent gastrointestinal symptoms such as diarrhea, nausea, vomiting, and abdominal pain. Other general symptoms may include headache, muscle pain (myalgia), fever, and sore throat. Septicemic plague progresses rapidly and can quickly cause life-threatening complications if not diagnosed and treated promptly.


Plague is caused by infection with the bacterium Yersinia pestis. This bacterium is found in wild rodents and their fleas. Some of the most commonly infected rodents are rats, squirrels, chipmunks or prairie dogs. Rabbits and hares (lagomorphs) may also carry the bacteria. The disease is most often transmitted to humans by the bite of infected fleas. Less frequently, direct contact with infectious animal tissue can also result in infection.

Pneumonic plague is the only manifestation of plague that can be transmitted from one person to another. This transmission occurs when a person breathes in (inhales) droplets from a coughing pneumonic plague patient. However, human-to-human transmission is extremely rare and has not occurred in the United States since 1924. Domestic cats can acquire pneumonic plague and transmit the infection to their owners in the same manner.

In recent years, plague has regained notoriety as a potential agent of bioterrorism. Most researchers believe that if used in such a manner, the bacteria would most likely be released as an aerosol with the intent of causing an outbreak of pneumonic plague.

Affected Populations

Plague affects males and females in roughly equal numbers. Seven human plague cases are reported on average in the United States each year. Most cases in the United States occur in the Southwest, especially in New Mexico, Colorado, Arizona, Utah and California. Human-to-human transmission has not occurred in the United States since 1924. Plague has a scattered worldwide distribution. Most cases occur in developing countries, especially in parts of Africa and Asia. Historically, plague has caused massive epidemics, most notably the Black Death of the Middle Ages.

Related Disorders

Symptoms of the following disorders can be similar to those of the plague. Comparisons may be useful for a differential diagnosis.

Tularemia is a rare infectious disease, caused by the bacterium Francisella tularensis, that most often affects small mammals such as rabbits, rodents and hares. It is highly infectious and is most often transmitted to humans by handling infected animal tissues or by infected tick or biting fly bite. Human-to-human transmission has not been documented. The severity of tularemia varies greatly. Some cases are mild and self-limiting; others may have serious complications, and a small percentage (about 2 percent) may become life-threatening. (For more information on this disorder, choose "tularemia" as your search term in the Rare Disease Database.)

Cat-scratch disease (also commonly known as cat-scratch fever) is a self- limiting infectious disease characterized by swelling and pain in the lymph nodes (regional lymphadenitis). Symptoms can vary from mild to severe, and may include achiness and discomfort (malaise), and/or loss of appetite (anorexia). The disease is caused by the bacterium Bartonella henselae and, in most cases, occurs as a result of a scratch, bite, or lick from a cat or kitten. Symptoms may not appear for several days after exposure and may last for several weeks. Although cat-scratch disease usually subsides without treatment, antibiotic and/or antimicrobial therapy may speed recovery. (For more information on this disorder, choose " Bartonellosis " as your search term in the Rare Disease Database.)

There are numerous other infections that cause similar symptoms to plague including Rocky Mountain spotted fever, lymphatic filariasis, brucellosis, dengue fever, and streptococcal lymphadenitis. (For more information on this disorder, choose the specific disorder name as your search term in the Rare Disease Database.)

Standard Therapies

The diagnosis of plague may be confirmed by specialized laboratory tests and characteristic clinical findings. Yersinia pestis can be identified in blood samples, tissue taken from enlarged lymph nodes (buboes) and sputum. All cases of plague in the United States must be reported to the appropriate state health department, which in turn notifies the Centers for Disease Control and Prevention (CDC).

The treatment of plague must begin as soon as possible to avoid serious life-threatening complications.

Streptomycin is approved by the FDA to treat plague. Additional antibiotics that have been used to treat plague include gentamicin, tetracyclines, fluoroquinolones and chloramphenicol. Levaquin (levofloxacin) was approved by the FDA in 2012 as a treatment for plague and to reduce the risk of getting plague after exposure to Yersinia pestis. Levaquin is manufactured by Janssen Pharmaceuticals.

When pneumonia has developed, extra care should be taken by health care providers to prevent transmission. There is no commercially available vaccine against plague in the United States.

Individuals living in plague endemic areas should take preventive measures such as avoiding contact with rodents and fleas.

Investigational Therapies

Researchers are investigating vaccines to prevent plague. Additional antibiotics are being investigated to determine their safety and effectiveness in treating plague.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:

For information about clinical trials conducted in Europe, contact:

Plague Resources



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Berkow R., ed. The Merck Manual-Home Edition.2nd ed. Whitehouse Station, NJ: Merck Research Laboratories; 2003:1107-8.

Morris JG. Yersinia Infections. In: Bennett JC, Plum F (eds.). Cecil Textbook of Medicine. 20th ed. W.B. Saunders Company. Orlando, FL;1996:1661-2

Mandell GL, Bennett JE, Dolan R. Eds. Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases. 4th ed. Churchill Livingstone Inc. New York, NY; 1995:2070-7.

Prentice MB, Rahalison L. Plague. Lancet. 2007;369:1196-207.
Human plague - four states, 2006. MMWR. 2006;55:940-3.

Riedel S. Plague: from natural disease to bioterrorism. Proc (Bayl Univ Med Cent). 2005;18:116-24.

Inglesby TV, et al. Working Group on Civil Biodefense. JAMA. 2000;283:2281-90.

Jefferson T, et al. Vaccines for preventing plague. Cochrane Database Syst Rev. 2000:CD000976.

Keeling MJ, Gilligan CA. Metapopulation dynamics of bubonic plague. Nature. 2000;407:903-06.

Fatal human plague-Arizona and Colorado, 1996. MMWR. 1997; 46:617-20.

Javaraman KS. Anti-plague efforts hindered by lack of recent experience. Nature. 1994;371: 467.

Butler T. Yersinia infectious: centennial of the discovery of the plague bacillus. Clin Infect Dis. 1994; 19: 655-61.

Wayangankar S, Jackson RL, Bronze MS, Minnaganti VR. Plague. Emedicine Journal, October 28, 2009. Available at: http://www.emedicine.com/MED/topic3381.htm Accessed:January 22, 2013.

Centers for Disease Control and Prevention. Available at: http://www.cdc.gov/plague Report last updated: November 28, 2012 Accessed:January 22, 2013.

Report last updated: 2013/02/04 00:00:00 GMT+0