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Plague is a serious, potentially life-threatening infectious disease that is usually transmitted to humans by the bites of rodent fleas. It was one of the scourges of early human history. There are three major forms of the disease: bubonic, septicemic, and pneumonic.


Plague has been responsible for three great world pandemics, which caused millions of deaths and significantly altered the course of history. A pandemic is a disease occurring in epidemic form throughout the entire population of a country, a people, or the world. Although the cause of the plague was not identified until the third pandemic in 1894, scientists are virtually certain that the first two pandemics were plague because a number of the survivors wrote about their experiences and described the symptoms.
The first great pandemic appeared in AD 542 and lasted for 60 years. It killed millions of citizens, particularly people living along the Mediterranean Sea. This sea was the busiest, coastal trade route at that time and connected what is now southern Europe, northern Africa, and parts of coastal Asia. This pandemic is sometimes referred to as the Plague of Justinian, named for the great emperor of Byzantium who was ruling at the beginning of the outbreak. According to the historian Procopius, this outbreak of plague killed 10,000 people per day at its height just within the city of Constantinople.
The second pandemic occurred during the fourteenth century, and was called the Black Death because its main symptom was the appearance of black patches (caused by bleeding) on the skin. It was also a subject found in many European paintings, drawings, plays, and writings of that time. The connections between large active trading ports, rats coming off the ships, and the severe outbreaks of the plague were understood by people at the time. This was the most severe of the three, beginning in the mid-1300s with an origin in central Asia and lasting for 400 years. Between a fourth and a third of the entire European population died within a few years after plague was first introduced. Some smaller villages and towns were completely wiped out.
The final pandemic began in northern China, reaching Canton and Hong Kong by 1894. From there, it spread to all continents, killing millions.
The great pandemics of the past occurred when wild rodents spread the disease to rats in cities, and then to humans when the rats died. Another route for infection came from rats coming off ships that had traveled from heavily infected areas. Generally, these were busy coastal or inland trade routes. Plague was introduced into the United States during this pandemic and it spread from the West towards the Midwest and became endemic in the Southwest of the United States.
About 10-15 Americans living in the southwestern United States contract plague each year during the spring and summer. The last rat-borne epidemic in the United States occurred in Los Angeles in 1924–25. Since then, all plague cases in this country have been sporadic, acquired from wild rodents or their fleas. Plague can also be acquired from ground squirrels and prairie dogs in parts of Arizona, New Mexico, California, Colorado, and Nevada. Around the world, there are between 1,000 and 2,000 cases of plague each year. Recent outbreaks in humans occurred in Africa, South America, and Southeast Asia.
Some people and/or animals with bubonic plague go on to develop pneumonia (pneumonic plague). This can spread to others via infected droplets during coughing or sneezing.
Plague is one of three diseases still subject to international health regulations. These rules require that all confirmed cases be reported to the World Health Organization (WHO) within 24 hours of diagnosis. According to the regulations, passengers on an international voyage who have been to an area where there is an epidemic of pneumonic plague must be placed in isolation for six days before being allowed to leave.
While plague is found in several countries, there is little risk to United States travelers within endemic areas (limited locales where a disease is known to be present) if they restrict their travel to urban areas with modern hotel accommodations.
Over the past few years, this infection primarily of antiquity has become a modern issue. This change has occurred because of the concerns about the use of plague as a weapon of biological warfare or terrorism (bioterrorism). Along with anthrax and smallpox, plague is considered to be a significant risk. In this scenario, the primary manifestation is likely to be pneumonic plague transmitted by clandestine aerosols. It has been reported that during World War II the Japanese dropped "bombs" containing plague-infected fleas in China as a form of biowarfare.

Causes and symptoms

Fleas carry the bacterium Yersinia pestis, formerly known as Pasteurella pestis. The plague bacillus can be stained with Giemsa stain and typically looks like a safety pin under the microscope. When a flea bites an infected rodent, it swallows the plague bacteria. The bacteria are passed on when the fleas, in turn, bite a human. Interestingly, the plague bacterium grows in the gullet of the flea, obstructing it and not allowing the flea to eat. Transmission occurs during abortive feeding with regurgitation of bacteria into the feeding site. Humans also may become infected if they have a break or cut in the skin and come in direct contact with body fluids or tissues of infected animals.
More than 100 species of fleas have been reported to be naturally infected with plague; in the western United States, the most common source of plague is the golden-manteled ground squirrel flea. Chipmunks and prairie dogs have also been identified as hosts of infected fleas.
Since 1924, there have been no documented cases in the United States of human-to-human spread of plague from droplets. All but one of the few pneumonic cases have been associated with handling infected cats. While dogs and cats can become infected, dogs rarely show signs of illness and are not believed to spread disease to humans. However, plague has been spread from infected coyotes (wild dogs) to humans. In parts of central Asia, gerbils have been identified as the source of cases of bubonic plague in humans.

Bubonic plague

Two to five days after infection, patients experience a sudden fever, chills, seizures, and severe
Plague is a serious infectious disease transmitted by the bites of rat fleas. There are three major forms of plague: bubonic, pneumonic, and septicemic. As illustrated above, fleas carry the bacterium Yersinia pestis. When a flea bites an infected rodent, it becomes a vector and then passes the plague bacteria when it bites a human.
Plague is a serious infectious disease transmitted by the bites of rat fleas. There are three major forms of plague: bubonic, pneumonic, and septicemic. As illustrated above, fleas carry the bacterium Yersinia pestis. When a flea bites an infected rodent, it becomes a vector and then passes the plague bacteria when it bites a human.
(Illustration by Electronic Illustrators Group.)
headaches, followed by the appearance of swellings or "buboes" in armpits, groin, and neck. The most commonly affected sites are the lymph glands near the site of the first infection. As the bacteria multiply in the glands, the lymph node becomes swollen. As the nodes collect fluid, they become extremely tender. Occasionally, the bacteria will cause an ulcer at the point of the first infection.

Septicemic plague

Bacteria that invade the bloodstream directly (without involving the lymph nodes) cause septicemic plague. (Bubonic plague also can progress to septicemic plague if not treated appropriately.) Septicemic plague that does not involve the lymph glands is particularly dangerous because it can be hard to diagnose the disease. The bacteria usually spread to other sites, including the liver, kidneys, spleen, lungs, and sometimes the eyes, or the lining of the brain. Symptoms include fever, chills, prostration, abdominal pain, shock, and bleeding into the skin and organs.

Pneumonic plague

Pneumonic plague may occur as a direct infection (primary) or as a result of untreated bubonic or septicemic plague (secondary). Primary pneumonic plague is caused by inhaling infective drops from another person or animal with pneumonic plague. Symptoms, which appear within one to three days after infection, include a severe, overwhelming pneumonia, with shortness of breath, high fever, and blood in the phlegm. If untreated, half the patients will die; if blood poisoning occurs as an early complication, patients may die even before the buboes appear.
Life-threatening complications of plague include shock, high fever, problems with blood clotting, and convulsions.


Plague should be suspected if there are painful buboes, fever, exhaustion, and a history of possible exposure to rodents, rabbits, or fleas in the West or Southwest. The patient should be isolated. Chest x rays are taken, as well as blood cultures, antigen testing, and examination of lymph node specimens. Blood cultures should be taken 30 minutes apart, before treatment.
A group of German researchers reported in 2004 on a standardized enzyme-linked immunosorbent assay (ELISA) kit for the rapid diagnosis of plague. The test kit was developed by the German military and has a high degree of accuracy as well as speed in identifying the plague bacillus. The kit could be useful in the event of a bioterrorist attack as well as in countries without advanced microbiology laboratories.


As soon as plague is suspected, the patient should be isolated, and local and state departments notified. Drug treatment reduces the risk of death to less than 5%. The preferred treatment is streptomycin administered as soon as possible. Alternatives include gentamicin, chloramphenicol, tetracycline, or trimethoprim/sulfamethoxazole.


Plague can be treated successfully if it is caught early; the mortality rate for treated disease is 1-15% but 40-60% in untreated cases. Untreated pneumonic plague is almost always fatal, however, and the chances of survival are very low unless specific antibiotic treatment is started within 15-18 hours after symptoms appear. The presence of plague bacteria in a blood smear is a grave sign and indicates septicemic plague. Septicemic plague has a mortality rate of 40% in treated cases and 100% in untreated cases.


Anyone who has come in contact with a plague pneumonia victim should be given antibiotics, since untreated pneumonic plague patients can pass on their illness to close contacts throughout the course of the illness. All plague patients should be isolated for 48 hours after antibiotic treatment begins. Pneumonic plague patients should be completely isolated until sputum cultures show no sign of infection.
Residents of areas where plague is found should keep rodents out of their homes. Anyone working in a rodent-infested area should wear insect repellent on skin and clothing. Pets can be treated with insecticidal dust and kept indoors. Handling sick or dead animals (especially rodents and cats) should be avoided.
Plague vaccines have been used with varying effectiveness since the late nineteenth century. Experts believe that vaccination lowers the chance of infection and the severity of the disease. However, the effectiveness of the vaccine against pneumonic plague is not clearly known.
Vaccinations against plague are not required to enter any country. Because immunization requires multiple doses over a 6-10 month period, plague vaccine is not recommended for quick protection during outbreaks. Moreover, its unpleasant side effects make it a poor choice unless there is a substantial long-term risk of infection. The safety of the vaccine for those under age 18 has not been established. Pregnant women should not be vaccinated unless the need for protection is greater than the risk to the unborn child. Even those who receive the vaccine may not be completely protected. The inadequacy of the vaccines available as of the early 2000s explains why it is important to protect against rodents, fleas, and people with plague. A team of researchers in the United Kingdom reported in the summer of 2004 that an injected subunit vaccine is likely to offer the best protection against both bubonic and pneumonic forms of plague.

Key terms

Bioterrorism — The use of disease agents to terrorize or intimidate a civilian population.
Buboes — Smooth, oval, reddened, and very painful swellings in the armpits, groin, or neck that occur as a result of infection with the plague.
Endemic — A disease that occurs naturally in a geographic area or population group.
Epidemic — A disease that occurs throughout part of the population of a country.
Pandemic — A disease that occurs throughout a regional group, the population of a country, or the world.
Septicemia — The medical term for blood poisoning, in which bacteria have invaded the bloodstream and circulates throughout the body.



Beers, Mark H., MD, and Robert Berkow, MD., editors. "Plague (Bubonic Plague; Pestis; Black Death)." In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.


Davis, S., M. Begon, L. DeBruyn, et al. "Predictive Thresholds for Plague in Kazakhstan." Science 304 (April 30, 2004): 736-738.
Gani, R., and S. Leach. "Epidemiologic Determinants for Modeling Pneumonic Plague Outbreaks." Emerging Infectious Diseases 10 (April 2004): 608-614.
Splettstoesser, W. D., L. Rahalison, R. Grunow, et al. "Evaluation of a Standardized F1 Capsular Antigen Capture ELISA Test Kit for the Rapid Diagnosis of Plague." FEMS Immunology and Medical Microbiology 41 (June 1, 2004): 149-155.
Titball, R. W., and E. D. Williamson. "Yersinia pestis (Plague) Vaccines." Expert Opinion on Biological Therapy 4 (June 2004): 965-973.
Velendzas, Demetres, MD, and Susan Dufel, MD. "Plague." eMedicine December 2, 2004.


Centers for Disease Control. 1600 Clifton Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 639-3311.
National Institute of Allergies and Infectious Diseases, Division of Microbiology and Infectious Diseases. Bldg. 31, Rm. 7A-50, 31 Center Drive MSC 2520, Bethesda, MD 20892.
World Health Organization. Division of Emerging and Other Communicable Diseases Surveillance and Control. 1211 Geneva 27, Switzerland.


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Gale Encyclopedia of Medicine. Copyright 2008 The Gale Group, Inc. All rights reserved.


an acute febrile, infectious, highly fatal disease caused by the bacillus Yersinia pestis. It is primarily a disease of rats and other rodents and is usually spread to human beings by fleas. The most common form is bubonic plague.Pneumonic plague is a second type, which can be spread directly between humans by droplet infection.

Plague is a devastating disease; three outbreaks in history wiped out whole populations. The first of these spread over Europe in the sixth century a.d. in a tremendous cycle of pestilence that lasted for more than 50 years. The second, called the “Black Death,” was perhaps the most deadly outbreak the world has ever known. It swept over Europe in the 14th century, and in many areas up to three quarters of the population perished; perhaps 25 million Europeans died. The “Great Plague of London” in 1665 was actually a relatively minor outbreak. A third great epidemic raged in Asia at the turn of the 20th century. The greatest toll was in India, where there were more than 12 million deaths from 1896 to 1933.

Some cases have occurred in the United States. Extensive epidemics have been prevented in this country by strict quarantines and by sanitation measures that have been enforced since the disease was traced to rat and wild rodent fleas.
Bubonic Plague. Bubonic plague is characterized by acutely inflamed and painful swellings of the lymph nodes, or buboes, usually in the groin. The disease strikes suddenly with chills and fever. Children may have convulsions. There is vomiting and thirst, generalized pain, headache, and mental dullness. Delirium may also be present. After the third day, black spots, which give the disease the name “black death,” may appear on the skin. Tender, enlarged lymph nodes are usually seen between the second and fifth days. Some cases of bubonic plague are mild. The more virulent cases last 5 or 6 days and are usually fatal. If the patient survives past the tenth or twelfth day, there is a good chance of recovery. The mortality rate for untreated cases is usually between 25 and 50 per cent, but has reached as high as 90 per cent. When antibiotic therapy is administered promptly (see Treatment), the mortality rate can be as low as 5 per cent.
Pneumonic Plague. Pneumonic plague usually occurs during outbreaks of bubonic plague and may be a direct complication of it. There is extensive involvement of the lungs, and the sputum contains many organisms. At one time, pneumonic plague was always fatal. Now, when antibiotic therapy is administered promptly (see Treatment), the mortality rate is much lower.
Prevention. The most important measure in controlling plague is the extermination of rats. This is especially necessary around shipping areas, in warehouses, and on docks. Rat control for ships arriving from plague areas is vital. Where there is an outbreak of plague, strict quarantine measures are called for, as well as the use of insecticides to protect inhabitants of the stricken area against fleas. Immunization with plague vaccine is recommended only for persons whose occupation requires contact with possibly infected rodents.

A consensus statement called “Plague as a Biological Weapon” has been issued by the Working Group on Civilian Biodefense. It notes the danger that would be associated with an aerosol plague weapon.
Treatment. Prompt treatment is essential with antibiotics, which can also be used for prophylaxis. Antibiotics of choice are streptomycin, gentamicin, tetracycline, and fluoroquinolones.
Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health, Seventh Edition. © 2003 by Saunders, an imprint of Elsevier, Inc. All rights reserved.


1. Any disease of wide prevalence or of excessive mortality.
2. An acute infectious disease caused by the bacterium Yersinia pestis and marked clinically by high fever, toxemia, prostration, a petechial eruption, lymph node enlargement, pneumonia, or hemorrhage from the mucous membranes; primarily a disease of rodents, transmitted to humans by fleas that have bitten infected animals. In humans the disease takes one of four clinical forms: bubonic plague, septicemic plague, pneumonic plague, or ambulant plague Synonym(s): pest, pestilence (1) , pestis
[G. plege, a stroke, a wound; L. plaga, a stroke, injury]
Farlex Partner Medical Dictionary © Farlex 2012


a. A highly infectious, usually fatal, epidemic disease; a pestilence.
b. A virulent, infectious disease that is caused by the bacterium Yersinia pestis (syn. Pasteurella pestis) and is transmitted primarily by the bite of fleas from an infected rodent, especially a rat. In humans it occurs in bubonic form, marked by lymph node enlargement, and in pneumonic form, marked by infection of the lungs, and can progress to septicemia.

plagu′er n.
The American Heritage® Medical Dictionary Copyright © 2007, 2004 by Houghton Mifflin Company. Published by Houghton Mifflin Company. All rights reserved.


Infectious disease An epidemic infection by Yersinia pestis spread to humans by fleas bitten by infected rodents–bubonic or septicemic plague or by inhalation of highly virulent encapsulated Y pestis when in close quarters with infected Pts–1º pneumonic plague Clinical forms Bubonic–90%, septicemic, pneumonic and, as a complication of any of these, meningitis Clinical Fever, chills, prostration, headache, N&V, diarrhea Treatment Streptomycin, tetracycline, chloramphenicol. See Bubonic plague, Fifth plague of Egypt.
McGraw-Hill Concise Dictionary of Modern Medicine. © 2002 by The McGraw-Hill Companies, Inc.


1. Any disease of wide prevalence or of excessive mortality.
2. An acute infectious disease caused by Yersinia pestis marked by high fever, toxemia, prostration, a petechial eruption, lymph node enlargement, and pneumonia, or hemorrhage from the mucous membranes; primarily a disease of rodents, transmitted to humans by fleas that have bitten infected animals. In humans, the disease takes one of four clinical forms: bubonic plague, septicemic plague, pneumonic plague, or ambulant plague.
Synonym(s): pestilence (1) .
See also: black death
[G. plege, a stroke, a wound; L. plaga, a stroke, injury]
Medical Dictionary for the Health Professions and Nursing © Farlex 2012


A serious infectious disease endemic in rats and spread to humans by rat fleas. Plague is caused by the organism Yersinia pestis and takes two main forms, bubonic and pneumonic. The latter is a complication of bubonic plague and can be spread by coughed droplets.

Bubonic plague features high fever, shivering, severe headache, painful swelling of the LYMPH NODES (buboes), especially in the groins, armpits and neck, seizures and, in untreated cases, death. SEPTICAEMIA and pneumonic plague are especially dangerous complications. Treatment is with antibiotics such as STREPTOMYCIN, TETRACYCLINE or CHLORAMPHENICOL. These reduce the mortality to less than 5%. Also known as the ‘black death’.

Collins Dictionary of Medicine © Robert M. Youngson 2004, 2005


Widely prevalent disease or one causing excessive mortality.
[G. plege, a stroke, a wound; L. plaga, a stroke, injury]
Medical Dictionary for the Dental Professions © Farlex 2012