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Plague
Classifications and external resources

Yersinia pestis seen at 2000x magnification. This bacterium, carried and spread by fleas, is the cause of the various forms of the disease plague
ICD-10	A20.
ICD-9	020
DiseasesDB	14226
MedlinePlus	000596
eMedicine	med/3381

Bubonic plague is the best-known variant of the deadly infectious disease plague, which is caused by the enterobacteria Yersinia pestis.

Contents 1 Infection/transportation 2 Types 3 Clinical features 4 Treatment 5 History 5.1 Historical plague epidemics 5.2 Historical Pandemics 5.2.1 Plague of Justinian 5.2.2 Black Death 5.2.3 Third Pandemic 6 Plague as a biological weapon 7 Contemporary cases 8 Uses in literature 9 See also 10 References 10.1 Numbered references 11 External links

[edit] Infection/transportation

Plague is primarily a disease of rodents, particularly marmots (in which the most virulent strains of plague are primarily found), but also black rats, prairie dogs, chipmunks, squirrels and other similar large rodents. Human infection most often occurs when a person is bitten by a rat flea (Xenopsylla cheopis) that has fed on an infected rodent. The bacteria multiply inside the flea, sticking together to form a plug that blocks its stomach and causes it to become very hungry. The flea then voraciously bites a host and continues to feed, even though it is unable to satisfy its hunger. During the feeding process, blood cannot flow into the blocked stomach, and consequently the flea vomits blood tainted with the bacteria back into the bite wound. The Bubonic plague bacterium then infects a new host, and the flea eventually dies from starvation. Any serious outbreak of plague is usually started by other disease outbreaks in rodents, or some other crash in the rodent population. During these outbreaks, infected fleas that have lost their normal hosts seek other sources of blood.

In 1894, two bacteriologists, the French Alexandre Yersin and the Japanese Shibasaburo Kitasato, independently isolated the responsible bacterium in Hong Kong during the Third Pandemic. Though both investigators reported their findings, a series of confusing and contradictory statements by Kitasato eventually led to the acceptance of Yersin as the primary discoverer of the organism. Yersin named it Pasteurella pestis in honour of the Pasteur Institute, where he worked, but in 1967 it was moved to a new genus, renamed Yersinia pestis in honour of Yersin. Yersin also noted that rats were affected by plague not only during plague epidemics but also often preceding such epidemics in humans, and that plague was regarded by many locals as a disease of rats: villagers in China and India asserted that, when large numbers of rats were found dead, plague outbreaks in people soon followed.

In 1898, the French scientist Paul-Louis Simond (who had also come to China to battle the Third Pandemic) established the rat-flea vector that drives the disease. He had noted that persons who became ill did not have to be in close contact with each other to acquire the disease. In Yunnan, China, inhabitants would flee from their homes as soon as they saw dead rats, and on the island of Formosa (Taiwan), residents considered handling dead rats a risk for developing plague. These observations led him to suspect that the flea might be an intermediary factor in the transmission of plague, since people acquired plague only if they were in contact with recently dead rats, but not affected if they touched rats that had been dead for more than 24 hours. In a now classic experiment, Simond demonstrated how a healthy rat died of plague after infected fleas had jumped to it from a plague-dead rat.

[edit] Types

Depending on the symptoms and the route of infection, plague appears in several forms, classified by the WHO with different ICD-10 codes:

Main disease:

(A20) Plague (Pestis). Infections caused by Yersinia pestis.

Forms:

(A20.0) Bubonic plague (Pestis bubonica) occurs when Yersinia pestis causes an inflammation of the lymph nodes, making them tender and swollen (from lat. bubo = bump). This is the most common form of plague.

(A20.1) Cellulocutaneous plague (Pestis cellulocutanea) is a very unusual form, with Yersinia pestis causing a skin infection.

(A20.2) Pneumonic plague or pulmonic plague (Pestis pneumonica) occurs when the lungs are infected by Yersinia pestis. The second most common form of plague. It may be a secondary infection, caused by bacteria spreading from the lymph nodes and reaching the lungs, but can also exist on its own, caused by inhalation of airborne bacteria.

(A20.3) Meningeal plague or plague meningitis (Pestis meningealis) looks like meningitis at the outset. It is most common in children and is usually the end result of ineffective treatment for other forms of plague. Unusual.

(A20.?) Pharyngeal plague occurs when Yersinia pestis is consumed, often through food. It can resemble tonsillitis. Very rare form.

(A20.7) Septicemic plague (Pestis septic(h)aemica) occurs when Yersinia pestis multiply in the blood. The third most common form. It is usually associated with hunting and skinning of animals, but can also occur secondary to bubonic and pneumonic plague.

(A20.8) Other forms of plague (Aliae formae pestis) include the milder forms abortive plague, asymptomatic plague and pestis minor, all three often resulting only in a mild fever and light swelling of the lymph glands, usually resolved in approximately a week if appropriate treatment is given.

[edit] Clinical features

Bubonic plague becomes evident three to seven days after the infection. Initial symptoms are chills, fever, diarrhea, headaches, and the swelling of the infected lymph nodes, as the bacteria replicate there. If untreated, the rate of mortality for bubonic plague is 50%.

In septicemic plague there is bleeding into the skin and other organs, which creates black patches on the skin. There are bite-like bumps on the skin, commonly red and sometimes white in the center. Untreated septicemic plague is universally fatal, but early treatment with antibiotics reduces the mortality rate to 4 to 15%.<ref name="Wagle1948">Wagle PM (1948). "Recent advances in the treatment of bubonic plague". Indian J Med Sci 2: 489–94.</ref><ref name="Meyer1950">Meyer KF (1950). "Modern therapy of plague". J Am Med Assoc 144: 982–5.</ref><ref name="DattGupta1948">Datt Gupta AK (1948). "A short note on plague cases treated at Campbell Hospital". Ind Med Gaz 83: 150–1.</ref> People who die from this form of plague often die on the same day symptoms first appear.

With pneumonic plague infecting lungs comes the possibility of person-to-person transmission through respiratory droplets. The incubation period for pneumonic plague is usually between two and four days, but can be as little as a few hours. The initial symptoms, of headache, weakness, and coughing with hemoptysis, are indistinguishable from other respiratory illnesses. Without diagnosis and treatment, the infection can be fatal in one to six days; mortality in untreated cases may be as high as 95%.

[edit] Treatment

An Indian doctor of Russian-Jewish origin Vladimir Havkin was the first to invent and test a plague vaccine.

The traditional treatments are:

• Streptomycin 30 mg/kg IM twice daily for 7 days
• Chloramphenicol 25–30 mg/kg single dose, followed by 12.5–15 mg/kg four times daily
• Tetracycline 2 g single dose, followed by 500 mg four times daily for 7–10 days (not suitable for children)

More recently,

• Gentamicin 2.5 mg/kg IV or IM twice daily for 7 days
• Doxycycline 100 mg (adults) or 2.2 mg/kg (children) orally twice daily

have also been shown to be effective.<ref name="Mwengee2006">Mwengee W et al. (2006). "Treatment of Plague with Genamicin or Doxycycline in a Randomized Clinical Trial in Tanzania". Clin Infect Dis 42 (5): 614–21.</ref>

[edit] History

[edit] Historical plague epidemics

The term 'plague' may refer at its broadest to any epidemic disease. Epidemic diseases in humans typically change in character over a relatively short period of time; syphilis appeared suddenly in Europe at the end of the 15th century; cholera has become less virulent in recent decades. Although the outbreak which began in China in 1855 is conventionally known as the Third Pandemic the First and Second Pandemics being, respectively, the Plague of Justinian and the Black Death, it is unclear whether there have been fewer, or more, than three major outbreaks of bubonic plague. Most modern outbreaks of bubonic plague amongst humans have been preceded by a striking, high mortality amongst rats, yet this phenomenon is absent from descriptions of some earlier plagues, especially the Black Death. The buboes, or swellings in the groin, that are especially characteristic of bubonic plague, are a feature of other diseases as well.

The earliest account describing a possible plague epidemic is found in I Samuel 5:6 of the Hebrew Bible. In this account, the Philistines of Ashdod were struck with a plague for the crime of stealing the Ark of the Covenant from the Children of Israel. These events have been dated to approximately the second half of the eleventh century B.C. The word "tumors" is used in most English translations to describe the sores that came upon the Philistines. The Hebrew, however, can be interpreted as "swelling in the secret parts". The account indicates that the Philistine city and its political territory were struck with a "ravaging of mice" and a plague, bringing death to a large segment of the population.

In the second year of the Peloponnesian War (430 B.C.), Thucydides described the coming of an epidemic disease which was reputed to have begun in Ethiopia, passed through Egypt and Libya, and then came to the Greek world. In this Plague of Athens the city lost possibly one third of its population, including Pericles (Speilvogal, J, 1999, pp. 56). Modern historians disagree on whether the plague was a critical factor in the loss of the war. This epidemic has long been considered an outbreak of plague. However, from Thucydides' description, more modern scholars dispute this, feeling that typhus, smallpox or measles may be better candidates. A recent study of the DNA found in the dental pulp of plague victims suggests that typhoid was actually responsible. Other scientists dispute these findings, citing serious methodologic flaws in the DNA study.

In the first century AD, Rufus of Ephesus, a Greek anatomist, refers to an outbreak of plague in Libya, Egypt, and Syria. He records that Alexandrian doctors named Dioscorides and Posidonius described symptoms including acute fever, pain, agitation, and delirium. Buboes—large, hard, and non-suppurating—developed behind the knees, around the elbows, and "in the usual places." The death toll of those infected was very high. Rufus also wrote that similar buboes were reported by a Dionysius Curtus, who may have practiced medicine in Alexandria in the third century B.C. If this is correct, the eastern Mediterranean world may have been familiar with bubonic plague at that early date. (ref. Simpson, W.J., Patrick, A.)

The last significant European outbreak of plague occurred in Russia in A.D. 1877–1889 in rural areas near the Ural Mountains and the Caspian Sea. This outbreak is sometimes seen as an extension of the Third Pandemic (see below). Efforts in hygiene and patient isolation reduced the spread of the disease, with approximately 420 deaths in the region. Significantly, the region of Vetlianka in this area is near a population of the bobak marmot, a small rodent considered a very dangerous plague reservoir.

[edit] Historical Pandemics

[edit] Plague of Justinian

For more complete information, see Plague of Justinian.

The Plague of Justinian in A.D. 541–542 is the first known pandemic on record, and marks the first firmly recorded pattern of bubonic plague. This outbreak is thought to have originated in Ethiopia or Egypt. The huge city of Constantinople imported massive amounts of grain, mostly from Egypt, to feed its citizens. The grain ships may have been the source of contagion for the city, with massive public granaries nurturing the rat and flea population. At its peak the plague was killing 5,000 people in Constantinople every day and ultimately destroyed perhaps 40 percent of the city's inhabitants. It went on to destroy up to a quarter of the human population of the eastern Mediterranean.

In A.D. 588 a second major wave of plague spread through the Mediterranean into what is now France. A maximum of 25 million dead is considered a reasonable estimate.

[edit] Black Death

For more complete information, see Black Death.

Image:Bubonic plague map.PNG During the mid-14th century, the Black Death, a massive and deadly pandemic, swept through Eurasia, killing approximately one third of the population (according to some estimates) and changing the course of Asian and European history. It is estimated that anywhere from a quarter to two-thirds of Europe's population became victims to the plague, making the Black Death the largest death toll from any known non-viral epidemic. While accurate statistical data does not exist, it is estimated that 1.4 percent of England's population, totaling 4.2 million, died while a higher percentage of individuals likely died in Italy. Northeastern Germany, Bohemia, Poland and Hungary, on the other hand, are believed to have suffered less while there are no estimates for Russia or the Balkans at all. Many scientists and historians believe the Black Death was an incidence of bubonic plague, with a strong presence of the more contagious pneumonic and septicemic varieties increasing the pace of infection, spreading the disease deep into inland areas of the continents. Some researchers have argued that the disease was more likely to have been viral (that is, not bubonic plague), pointing to the absence of rats from some parts of Europe that were badly affected and to the conviction of people at the time that the disease was spread by direct human contact.

The Black Death continued to strike parts of Europe throughout the 14th century, the 15th century and the 16th century with varying degrees of intensity and fatality. Researchers still do not agree on why large outbreaks of the infection have not returned to Europe; however, changes in hygiene habits and strong efforts within public health and sanitation probably had a significant impact on the rate of infection. Genetic selection for resistance amongst humans may also have contributed.

[edit] Third Pandemic

For more complete information see Third Pandemic.

The Third Pandemic began in China in 1855, spreading plague to all inhabited continents and ultimately killing more than 12 million people in India and China alone. Casualty patterns indicate that waves of this pandemic may have come from two different sources. The first was primarily bubonic and was carried around the world through ocean-going trade, transporting infected persons, rats, and cargos harboring fleas. The second, more virulent strain was primarily pneumonic in character, with a strong person-to-person contagion. This strain was largely confined to Manchuria and Mongolia. Researchers during the "Third Pandemic" identified plague vectors and the plague bacterium (see above), leading in time to modern treatment methods.

Unfourtnatly, Bubonic bacteria killed 1/3 of the population in Asia.

[edit] Plague as a biological weapon

Plague has a long history as a biological weapon. Historical accounts from medieval Europe detail the use of infected animal carcasses, such as cows or horses, and human carcasses, by Mongols, Turks and other groups, to contaminate enemy water supplies. Plague victims were also reported to have been tossed by catapult into cities under siege.

During World War II, the Japanese Army developed weaponised plague, based on the breeding and release of large numbers of fleas. During the Japanese occupation of Manchuria, Unit 731 deliberately infected civilians and prisoners of war with the plague bacterium. These subjects, called "logs", were then studied by dissection, some while still living and conscious. After World War II, both the United States and the Soviet Union developed means of weaponising pneumonic plague. Experiments included various delivery methods, vacuum drying, sizing the bacterium, developing strains resistant to antibiotics, combining the bacterium with other diseases, such as diphtheria, and genetic engineering. Scientists who worked in USSR bio-weapons programs have stated that the Soviet effort was formidable and that large stocks of weaponised plague bacteria were produced. Information on many of the Soviet projects is largely unavailable. Aerosolized pneumonic plague remains the most significant threat.

[edit] Contemporary cases

The disease still exists in wild animal populations from the Caucasus Mountains east across southern and central Russia, to Kazakhstan, Mongolia, and parts of China; in Southwest and Southeast Asia, Southern and East Africa (including the island of Madagascar); in North America, from the Pacific Coast eastward to the western Great Plains, and from British Columbia south to Mexico; and in South America in two areas: the Andes mountains and Brazil. There is no plague-infected animal population in Europe or Australia.

• In modern London, the rat is a growing problem, and not just growing in numbers. They are also much bigger -- the average brown rat, Rattus norvegicus, is normally under a foot long and is a scrawny scavenger weighing in at less than a pound. However, London rat-catchers now report finding them twice that size.[1]

• On 15 September, 2005, ABC News reported[2] that three mice infected with Yersinia pestis apparently disappeared from a laboratory belonging to the Public Health Research Institute, located on the campus of the University of Medicine and Dentistry of New Jersey, which conducts anti-bioterrorism research for the United States government.
• On 19 April, 2006, CNN News and others reported a case of plague in Los Angeles, California, the first reported case in that city since 1984.
• On 16 May, 2006, KSL[3] reported a case of plague found in small vermin at Natural Bridges about 40 miles west of Blanding in San Juan County, Utah
• On 28 June, 2006, AZ Central[4] reported a case of plague found in a cat.
• In the U.S., about half of all human cases of plague since 1970 have occurred in New Mexico. There were 2 plague deaths in the state in 2006, the first fatalities in 12 years.[5]
• One hundred deaths resulting from pneumonic plague were reported in Ituri district of the eastern Democratic Republic of the Congo in June 2006. Control of the plague was proving difficult due to the ongoing conflict.<ref>DR Congo 'plague' leaves 100 dead, BBC News, 14 June 2006</ref>

[edit] Uses in literature

• The Decameron by Giovanni Boccaccio (1350). Takes place in Florence in 1348, during the outbreak of the "Black Death", widely believed to be Bubonic Plague.
• A Journal of the Plague Year by Daniel Defoe (1722). A fictional first hand account of the London outbreak of 1665.
• The Masque of the Red Death (1842) by Edgar Allan Poe includes a vivid description of pestilence conventionally agreed to be septicemic plague.
• I Promessi Sposi (The Betrothed) (1842) by Alessandro Manzoni set in early 17th century in Northern Italy, is one of the most read and better known classical novels in Italian literature. Contains a detailed and vivid account of society during the plague outbreak in its time.
• Narcissus and Goldmund by Hermann Hesse (1930). A fictional account in which the main character ends up witnessing the effects of the plague first-hand.
• The Plague by Albert Camus (1947) depicts an outbreak of plague at the Algerian city of Oran. The disease, often interpreted as a metaphor for the German occupation of France in World War II, serves as a means for the author to examine his characters' responses to hardship, suffering and death.
• The Black Death by Gwyneth Cravens and John S Marr (1977) is a disaster novel depicting an outbreak of plague in present-day New York City through the eyes of health workers and government officials.
• Doomsday Book by Connie Willis (1992). A Hugo award and Nebula award-winning historical science fiction novel, in which a time-traveler inadvertently ends up in the plague-ridden England of 1348.
• The Plague Dogs (1977), by Richard Adams. A fictional story in which two dogs, Rowf and Snitter, escape from a British government research laboratory and are hunted down by the government as potential carriers of the Plague.
• The Years of Rice and Salt by Kim Stanley Robinson (2002). Presents an alternate history of the world where the population of Europe is obliterated by the Black Death setting the stage for a world without Europeans and Christianity.
• Year of Wonders: A Novel of the Plague by Geraldine Brooks (2002). Based on a historical village (see Eyam) whose denizens quarantined themselves to avoid further spread of the disease.
• An episode of the television show NCIS focuses on one of the major characters becoming infected with genetically altered strain of Y Pestis.
• In season 3, episode 1 of the television show Grey's Anatomy, a suspected case of the plague results in quarantines throughout the hospital.

[edit] See also

• Plague (disambiguation page)
• Black Death
• Epidemic
• Medieval demography
• Plague of Justinian
• Third Pandemic
• Ring around the rosey
• List of Bubonic plague outbreaks
• Plague columns
• Plague doctor

[edit] References

[edit] External links

• World Health Organization
  • Health topic
  • Communicable Disease Surveillance & Response - Impact of plague & Information resources
• Centers for Disease Control and Prevention
  • CDC Plague map world distribution, publications, information on bioterrorism preparedness and response regarding plague
  • Infectious Disease Information more links including travelers' health
• Symptoms, causes, pictures of bubonic plague
• Secrets of the Dead . Mystery of the Black Death PBS
• Flea As Weapon

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