Plague

Definition

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

Description

Plague was one of the scourges of early human history. It 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.

Risk factors

Plague occurs in areas where the bacteria are present in wild rodent populations. The risks are generally highest in rural areas, including homes that provide food and shelter for various rodents, such as ground squirrels, chipmunks and wood rats.

While plague is found in several countries, there is little risk to United States travelers within endemic areas (regions where a disease is known to be present) if they travel to urban areas with modern hotel facilities.

Demographics

According to the Centers for Disease Control (CDC), between 1900 and 2016, 1,040 confirmed or probable human plague cases occurred in the United States. Over 80% of cases have been the bubonic form. In recent decades, an average of 7 human plague cases are reported each year. Plague has occurred in people of all ages (infants up to age 96), though 50% of cases occur in people ages 12–45. Plague is most common in the southwestern states, particularly New Mexico, Arizona, and Colorado. Most cases in the United States are acquired from late spring to early fall. 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.

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 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.

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.
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

Life-threatening complications of plague include shock, high fever, problems with blood clotting, and convulsions.

Diagnosis

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.

Treatment

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.

Public health role and response

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.

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.

QUESTIONS TO ASK YOUR DOCTOR

Prognosis

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.

Prevention

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.

See also Pandemic ; Rodents ; Vaccination .

Resources

BOOKS

Aberth, John. Plagues in World History. Lanham, MD: Rowman & Littlefield Publishers, 2011.

Beers, Mark H., Robert S. Porter, and Thomas V. Jones, eds. The Merck Manual of Diagnosis and Therapy. 18th ed. Whitehouse Station, NJ: Merck Research Laboratories, 2006.

Slack, Paul. Plague: A Very Short Introduction. New York, NY: Oxford University Press, 2012.

PERIODICALS

Bitam, Idir, et al. “Fleas and flea–borne diseases.” International Journal of Infectious Diseases (August 2010): 667–676.

Chouikha, I., and B. J. Hinnebusch. “Yersinia––flea interactions and the evolution of the arthropod–borne transmission route of plague.” Current Opinion in Microbiology 15, no. 3 (June 2012): 239–246.

Gage, K. L. “Factors affecting the spread and maintenance of plague.” Advances in Experimental Medicine and Biology 953 (2012): 79–94.

Oyston, P. C., and E. D. Williamson. “Modern Advances against Plague.” Human Pathology 81 (2012): 209–241.

WEBSITES

Plague. Centers for Disease Control. http://www.cdc.gov/plague/ (accessed June 13, 2012).

Plague. Medline Plus. http://www.nlm.nih.gov/medlineplus/ plague.html (accessed June 6, 2012).

Plague. NIAID. http://www.niaid.nih.gov/topics/plague/ pages/default.aspx (accessed October 13, 2012).

ORGANIZATIONS

Centers for Disease Control and Prevention (CDC), 1600 Clifton Road, Atlanta, GA, 30333, (800) 232-4636, cdcinfo@cdc.gov, http://www.cdc.gov .

National Institute of Allergies and Infectious Diseases, 6610 Rockledge Drive, MSC 6612, Bethesda, MD, 208926612, ((301)) 496-5717, Fax: ((301)) 402-3573, ((866)) 284-4107, ocpostoffice@niaid.nih.gov, http://www.niaid.nih.gov .

World Health Organization (WHO), Avenue Appia 201211, Geneva, Switzerland, 27, 41 22 791-2111, info@who.int, http://www.who.int .

Arnold Cua, MD
Rebecca J. Frey, PhD

  This information is not a tool for self-diagnosis or a substitute for professional care.