Plague, Modern History

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Plague, Modern History


Disease History, Characteristics, and Transmission

Scope and Distribution

Treatment and Prevention

Impacts and Issues



Plague is a greatly feared disease that has killed millions of people since medieval times. It is caused by the bacterium Yersinia pestis, which is carried by fleainfested rodents, and mortality rates are more than 50% if the disease is left untreated. The third pandemic of plague extended into the twentieth century and stimulated research into the cause and transmission of the disease.

There have been no major epidemics of plague in the United States for many years, although occasional cases still occur in the southwestern states. Globally, from 1,000 to 3,000 cases annually are reported to the World Health Organization (WHO), most of which occur in Africa, Southeast Asia, and Latin America. It may not be possible to eradicate plague, but outbreaks can be prevented by reducing rodent populations. Constant vigilance regarding plague is also necessary because it has some potential as an agent of a bioterrorist attack.

Disease History, Characteristics, and Transmission

Yersinia pestis is a Gram-negative bacillus—rod-shaped— bacterium, which was discovered as the cause of plague by the Swiss researcher Alexander Yersin in 1894. The term Gram-negative refers to the way in which the bacterium absorbs the Gram stain used to prepare bacterial cultures for microscopy. The incubation period of Y. pestis is between two and eight days, and the microbe produces three types of plague: bubonic, pneumonic, and septicemic.

Bubonic plague accounts for 90–95% of all cases and is marked by sudden onset of fever, chills, weakness, and headache. Initially, these could be mistaken for flu symptoms. Shortly after, multiplication of the bacteria within the lymph glands of the armpits and groin cause characteristic swellings, called buboes, which are extremely tender, typically 0.8–4 in (2–10 cm) in diameter, and hot to the touch.

The disease often progresses to bleeding from the gastrointestinal, respiratory or genitourinary tract—leading to the name “Red Death.” Gangrene—death of tissue from lack of oxygen—may occur on the nose or penis, leading to the name “Black Death.” This name also was given to some of the plague epidemics in history. These complications are caused by the spread of the bacterium throughout the bloodstream and the effects of associated toxins. Untreated bubonic plague has a death rate of more than 50%.

Pneumonic plague may occur as a complication of bubonic plague, and also accounts for 5% of primary cases. Symptoms include bloody sputum, chest pain, coughing, and breathlessness. The disease is highly infectious and 100% fatal if left untreated. Septicemic plague has similar symptoms to bubonic plague—apart from the buboes—and accounts for around 5% of cases, with extensive bloodstream infection being the most significant feature.

Plague is a zoonosis—a disease of animals that can infect humans. Rodents act as the animal reservoir for the disease. When fleas bite an animal infected with Y. pestis, they can carry the disease to other rodents. The animals become sick, and when they start to die, the fleas will seek out human hosts as an alternative source of blood meals. The main flea vector is the oriental rat flea, Xenopsylla cheopsis.

Humans generally become infected with plague through the bite of an infected flea or from handling an infected animal and coming into contact with its tissues or body fluids. In the United States, wild rodents are the most common animal reservoirs for plague, with the rock squirrel being implicated in the majority of cases in the Southwest. In the Pacific States, the California ground squirrel is the most important source of plague. Prairie dogs, wood rats, chipmunks, and other burrowing rodents have also been involved in U.S. cases of plague. Other, less frequent, sources include wild rabbits, wild carnivores, and domestic cats and dogs, who pick up infected fleas from wild rodents. In addition, pneumonic plague can be spread from person-to-person through inhalation of infected secretions.

The Y. pestis bacteria quickly enter the bloodstream and enter white blood cells, where they multiply and produce toxins. They spread throughout the blood and may cause disseminated intravascular coagulation— multiple tiny blood clots—which lead to the complications of plague.


BIOWEAPON: A weapon that uses bacteria, viruses, or poisonous substances made by bacteria or viruses.

BUBO: A swollen lymph gland, usually in the groin or armpit, characteristic of infection with bubonic plague.

EPIDEMIC: From the Greek epidemic, meaning “prevalent among the people,” is most commonly used to describe an outbreak of an illness or disease in which the number of individual cases significantly exceeds the usual or expected number of cases in any given population.

FLEA: A flea is any parasitic insect of the order Siphonaptera. Fleas can infest many mammals, including humans, and can act as carriers (vectors) of disease.

GRAM-NEGATIVE BACTERIA: All types of bacteria identified and classified as a group that does not retain crystal-violet dye during Gram's method of staining.

MULTI-DRUG RESISTANCE: Multi-drug resistance is a phenomenon that occurs when an infective agent loses its sensitivity against two or more of the drugs that are used against it.

NOTIFIABLE DISEASE: A disease that the law requires must be reported to health officials when diagnosed; also called a reportable disease.

PANDEMIC: Pandemic, which means all the people, describes an epidemic that occurs in more than one country or population simultaneously.

RESERVOIR: The animal or organism in which the virus or parasite normally resides.

ZOONOSES: Zoonoses are diseases of microbiological origin that can be transmitted from animals to people. The causes of the diseases can be bacteria, viruses, parasites, and fungi.

Scope and Distribution

Plaque has been responsible for three known pandemics during the course of human history. The first began in the middle of the sixth century and is known as the Justinian plague. It was followed in the middle of the fourteenth century by the pandemic popularly known as the Black Death. The Third or Modern pandemic of plague began in the mid-1800s in China and spread throughout the world to cause nearly 30 million cases and over 12 million deaths between 1896 and 1930.

By the time of the Third pandemic, scientists had developed methods for investigating microbial causes of disease that could be applied to this serious public health problem. Alexander Yersin discovered Y. pestis in 1894 and the transmission of plague via fleas was reported by Paul-Louis Simond in 1890. This new understanding, together with the later introduction of antibiotics, meant that plague began to exact less of a toll on human life in many countries. Modern techniques of analyzing DNA have led to new insights into ancient cases of plague from previous pandemics, using samples from the dental pulp of victims’ remains.

Today plague causes both sporadic cases and epidemics involving hundreds of people, the numbers involved depending upon geographical location. The disease is found in Africa, Southeast Asia, Latin America, and in the southwestern United States. In Africa, there have been severe outbreaks in recent years in Kenya, Tanzania, Zaire, Botswana, and Mozambique. Smaller outbreaks have occurred in other East African countries. Sporadic cases have been reported from North and West Africa. The disease also occurs regularly in Madagascar, where multi-drug resistance has been reported. In Asia, countries that are particularly affected by plague include Burma (Myanmar), Vietnam, and Indonesia. In Latin America, plague is found in the Andean mountain region and in Brazil. However, there is no plague today in Australia or Europe.

In North America, most human cases of plague occur in two specific regions. One is in northern New Mexico, northern Arizona, and southern Colorado. The other is in California, southern Oregon, and far western Nevada. The highest rates are in Native Americans, particularly Navajos, hunters, veterinarians and pet owners handling infected animals, and among campers or hikers entering areas with outbreaks of animal plague. The last urban epidemic of plague in the United States occurred in Los Angles in 1924–1925.

Worldwide, between 1,000 and 3,000 cases of plague are reported to the WHO each year. In 2003, there were 2,118 cases reported from nine countries, including 182 deaths. Nearly all of these came from Africa. In the United States, there is an average of around 15 cases of plague each year, of which one in seven proves fatal. In Africa, Asia, and Latin America there were major outbreaks each year in the 1980s. These cases tend to be associated with domestic rats and were more common among those living in small towns, villages, and agricultural areas than among the population in urban areas.

The major risk factor for epidemic plague is poor living conditions with rodent and flea infestation, coupled with human overcrowding. Lab workers handling plague bacteria are also at high risk wherever they are located.

The WHO received reports of outbreaks of pneumonic plague in the Democratic Republic of Congo (DRC) in 2005 and 2006. The disease has long been endemic in the Ituri region, and, indeed, this region is the most active natural focus of plague in the world today. There was an outbreak near the town of Zobia, in mid–2005 in a forest area that had attracted several thousand people responding to reports of the discovery of diamonds there. The outbreak involved 124 cases of pneumonic plague and 56 deaths. Investigators from the WHO found suspect rodents and poor sanitary conditions at the affected site. The situation was made worse by panic, with many people fleeing the outbreak and dying along forest trails, spreading this highly infectious disease. It was no surprise, therefore, when there were further outbreaks in the DRC in the months following.

In October 2006, there were apparently 626 more suspected cases of pneumonic plague, including 42 deaths, in the DRC. But this would be an unusually low death rate for pneumonic plague, so the WHO thought there might have been an over-estimation of the number of cases. A team from the humanitarian group Médicins sans Frontières (Doctors without Borders) worked with the WHO and the local health authority in Congo doing lab tests, case management, and contact tracing to bring the outbreak under control. However, further outbreaks are almost inevitable and, if they occur in a city, many deaths will result.

Plague is notifiable to the Centers for Disease Control and Prevention (CDC) whose center in Fort Collins, Colorado, is a WHO Collaborating Center for Reference and Research on Plague Control, reporting all human plague cases in the United States to the WHO. Also, the National Notifiable Disease Surveillance System carries out surveillance on animal plague, reports human cases, and carries out lab testing on fleas, animal tissues, and blood samples.

Treatment and Prevention

Antibiotic treatment reduces the mortality rate of plague from over 50% to around 10%. Streptomycin is the preferred drug, but tetracycline or chloramphenicol can be used as alternatives. Anyone with plague must be isolated and hospitalized. However, given prompt diagnosis and treatment, nearly everyone with plague can expect to recover.

The contacts of plague cases must be traced and treated with antibiotics to help stop the infection from developing. They should also be disinfested of any fleas they may be carrying. Passengers traveling back from plague endemic areas are generally subject to quarantine regulations in case they are incubating the disease.

Preventive antibiotics can be taken if someone has been exposed to the bites of wild rodent fleas during an outbreak, or to the tissues or fluids of a plague-infected animal. The same treatment is appropriate for those who have been exposed to a person or pet with suspected plague, especially if it is pneumonic plague. Tetracycline, chloramphenicol, or sulfonamide antibiotics are preferred for this kind of prophylactic treatment. However, since multi-drug resistance has begun to emerge in Madagascar, it has to be assumed that it could also happen elsewhere.

Although vaccines against plague have been used in the past, these are not available in the United States currently. Research has shown that the vaccine does not help reduce the number of cases or the spread of infection during an outbreak. However, it may have a role to play in protecting those who are repeatedly exposed through lab or healthcare work.

Prevention of plague among the population currently depends upon controlling fleas and rodents. People living in those regions of the United States where plague infection is active need to take care to avoid exposure. Sick or dead rodents, which may be infected with plague, should be reported to local health authorities and should never be handled.

Keeping homes, workplaces, and recreation areas clear of food and nesting places for rodents is extremely important. Junk, firewood, and rock piles should be removed to make these places rodent-proof. Insect repellents applied to clothing and skin can reduce the risk of exposure to potentially infected fleas. Cats and dogs need to be regularly treated with flea control agents and should not be allowed to roam freely, in case they come into contact with infected rodents. Investigation of outbreaks and sporadic cases of plague often lead to the identification of a clustered area of animal die-offs that is the exposure source and needs to be disposed of.

Impacts and Issues

Plague has been a public health problem for several centuries and, unlike polio and smallpox, it is unlikely that it can ever be eradicated. Between outbreaks, Y. pestis lives on in certain rodent populations without actually wiping them out, thereby constituting a silent, long-term reservoir of infection. The best that can be hoped for is to employ control and precautionary measures in those places where humans and flea-infested rodents are likely to interact.

Although sporadic cases of plague do occur in the southwestern United States, these can be avoided as far as possible with common sense precautions regarding contact with potentially infected rodents. Efforts to control plague probably need to be focused where conditions create a risk of disease outbreak or even epidemics. This means managing unsanitary rat-infested environments to make places where people live, work, or play safer.

Control of rat populations in rural and urban areas of many less developed countries has not yet been achieved to the extent that it has in most developed countries. Close surveillance of both rodents and humans for plague is the first step in tightening controls. Insecticides can be used to control rodent fleas in danger areas and efforts made to reduce the local population of rodents in human inhabited areas by removing potential food sources and nesting sites.

In the future, however, plague may become even more unpredictable. Changing climate, due to global warming, and population movements may create new environments where flea-infested rodents can flourish and put people at risk of plague.

A further threat of the spread of plague comes from its potential use as a bioweapon. The concern centers around pneumonic plague, which is highly infectious and can spread rapidly from person to person. An aerosol-based biological weapon could introduce Y. pestis into the population without warning, causing a severe epidemic within just a few days. Containment would depend upon rapid detection of cases and treatment of these people, and their contacts, with antibiotics within 24 hours. Public health authorities in the United States—probably a potential major target for such an attack—do hold large stocks of the appropriate antibiotics, and the CDC says these could be made available anywhere to any location where they are needed within 12 hours.

People may, however, feel more reassured if they were already vaccinated against plague, rather than hoping that the response to an attack will be prompt and sufficiently effective. However, there is currently no plague vaccine available in the United States. Research into such a vaccine by academics and the U.S. Army is ongoing, but the CDC says it will be several years before one becomes widely available.

The threat of bioterrorism has re-focused attention on plague as a disease problem that has been largely absent from developed countries, including the United States, for many years except in sporadic form. In many African countries and in parts of Southeast Asia, plague is still an endemic public health issue that leads to hundreds of deaths each year. The U.S. bioterrorism effort can learn from what is known of the natural history of plague in other countries and use molecular technologies to better understand the disease. A bioterrorist attack with Y. pestis may never happen, but the knowledge gained in preparing for a potential attack may help better diagnosis, treatment, and prevention efforts in those places where the disease occurs naturally.

See AlsoPlague, Early History.



Wilson, Walter R., and Merle A. Sande. Current Diagnosis & Treatment in Infectious Diseases. New York: McGraw Hill, 2001.


Drancourt, M., and D. Raoult. “Molecular Insights into the History of Plague.” Microbes and Infection 4 (January 2002): 105–109.

Web Sites

Centers for Disease Control and Prevention. “CDC Plague Home Page.” <> (accessed May 13, 2007).

Centers for Infectious Diseases Research and Policy. “Plague Outbreak Highlighted Ongoing Problem in Africa.” May 27, 2005. <> (accessed May 13, 2007).

Susan Aldridge