Bubonic plague

Bubonic plague

Overview
Plague is a deadly infectious disease
Infectious disease
Infectious diseases, also known as communicable diseases, contagious diseases or transmissible diseases comprise clinically evident illness resulting from the infection, presence and growth of pathogenic biological agents in an individual host organism...

 that is caused by the enterobacteria
Enterobacteriaceae
The Enterobacteriaceae is a large family of bacteria that includes many of the more familiar pathogens, such as Salmonella, Escherichia coli, Yersinia pestis, Klebsiella and Shigella. This family is the only representative in the order Enterobacteriales of the class Gammaproteobacteria in the...

 Yersinia pestis
Yersinia pestis
Yersinia pestis is a Gram-negative rod-shaped bacterium. It is a facultative anaerobe that can infect humans and other animals....

, named after the French-Swiss bacteriologist Alexandre Yersin
Alexandre Yersin
Alexandre Emile Jean Yersin was a Swiss and French physician and bacteriologist. He is remembered as the co-discoverer of the bacillus responsible for the bubonic plague or pest, which was later re-named in his honour .Yersin was born in 1863 in Aubonne, Canton of Vaud, Switzerland, to a family...

. Primarily carried by rodents (most notably rat
Rat
Rats are various medium-sized, long-tailed rodents of the superfamily Muroidea. "True rats" are members of the genus Rattus, the most important of which to humans are the black rat, Rattus rattus, and the brown rat, Rattus norvegicus...

s) and spread to humans via fleas, the disease is notorious throughout history, due to the unrivaled scale of death and devastation it brought. Until June 2007, plague was one of only three diseases specifically reportable to the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

 (the two other ones were cholera
Cholera
Cholera is an infection of the small intestine that is caused by the bacterium Vibrio cholerae. The main symptoms are profuse watery diarrhea and vomiting. Transmission occurs primarily by drinking or eating water or food that has been contaminated by the diarrhea of an infected person or the feces...

 and yellow fever
Yellow fever
Yellow fever is an acute viral hemorrhagic disease. The virus is a 40 to 50 nm enveloped RNA virus with positive sense of the Flaviviridae family....

).
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Timeline

1349   Six thousand Jews are killed in Mainz after being blamed for the bubonic plague.

1894   Kitasato Shibasaburō discovers the infectious agent of the bubonic plague and publishes his findings in ''The Lancet''.

1907   Bubonic plague breaks out in San Francisco, California.

 
Encyclopedia
Plague is a deadly infectious disease
Infectious disease
Infectious diseases, also known as communicable diseases, contagious diseases or transmissible diseases comprise clinically evident illness resulting from the infection, presence and growth of pathogenic biological agents in an individual host organism...

 that is caused by the enterobacteria
Enterobacteriaceae
The Enterobacteriaceae is a large family of bacteria that includes many of the more familiar pathogens, such as Salmonella, Escherichia coli, Yersinia pestis, Klebsiella and Shigella. This family is the only representative in the order Enterobacteriales of the class Gammaproteobacteria in the...

 Yersinia pestis
Yersinia pestis
Yersinia pestis is a Gram-negative rod-shaped bacterium. It is a facultative anaerobe that can infect humans and other animals....

, named after the French-Swiss bacteriologist Alexandre Yersin
Alexandre Yersin
Alexandre Emile Jean Yersin was a Swiss and French physician and bacteriologist. He is remembered as the co-discoverer of the bacillus responsible for the bubonic plague or pest, which was later re-named in his honour .Yersin was born in 1863 in Aubonne, Canton of Vaud, Switzerland, to a family...

. Primarily carried by rodents (most notably rat
Rat
Rats are various medium-sized, long-tailed rodents of the superfamily Muroidea. "True rats" are members of the genus Rattus, the most important of which to humans are the black rat, Rattus rattus, and the brown rat, Rattus norvegicus...

s) and spread to humans via fleas, the disease is notorious throughout history, due to the unrivaled scale of death and devastation it brought. Until June 2007, plague was one of only three diseases specifically reportable to the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

 (the two other ones were cholera
Cholera
Cholera is an infection of the small intestine that is caused by the bacterium Vibrio cholerae. The main symptoms are profuse watery diarrhea and vomiting. Transmission occurs primarily by drinking or eating water or food that has been contaminated by the diarrhea of an infected person or the feces...

 and yellow fever
Yellow fever
Yellow fever is an acute viral hemorrhagic disease. The virus is a 40 to 50 nm enveloped RNA virus with positive sense of the Flaviviridae family....

). Depending on lung infection, or sanitary conditions, plague also can be spread in the air, by direct contact, or by contaminated undercooked food or materials. The symptoms of plague depend on the concentrated areas of infection in each person: such as bubonic plague
Bubonic plague
Plague is a deadly infectious disease that is caused by the enterobacteria Yersinia pestis, named after the French-Swiss bacteriologist Alexandre Yersin. Primarily carried by rodents and spread to humans via fleas, the disease is notorious throughout history, due to the unrivaled scale of death...

 in lymph nodes, septicemic plague
Septicemic plague
Septicemic plague is a deadly blood infection, one of the three main forms of plague. It is caused by Yersinia pestis, a gram-negative bacterium....

 in blood vessels, pneumonic plague
Pneumonic plague
Pneumonic plague, a severe type of lung infection, is one of three main forms of plague, all of which are caused by the bacterium Yersinia pestis. It is more virulent and rare than bubonic plague...

 in lungs, and so on. Medicines can cure plague if detected early. Plague is still endemic
Endemic (epidemiology)
In epidemiology, an infection is said to be endemic in a population when that infection is maintained in the population without the need for external inputs. For example, chickenpox is endemic in the UK, but malaria is not...

 in some parts of the world.

Name


The epidemiological use of the term "plague" is currently applied to bacterial infections that cause bubo
Bubo
Bubo may refer to:* A bubo, a rounded swelling on the skin of a person afflicted by the bubonic plague.* Bubo, the horned owl and eagle-owl genus.* Bubo, a mechanical owl in the 1981 film Clash of the Titans...

es
, although historically the medical use of the term "plague" has been applied to pandemic
Pandemic
A pandemic is an epidemic of infectious disease that is spreading through human populations across a large region; for instance multiple continents, or even worldwide. A widespread endemic disease that is stable in terms of how many people are getting sick from it is not a pandemic...

 infections in general. Plague is often synonymous with "bubonic plague
Bubonic plague
Plague is a deadly infectious disease that is caused by the enterobacteria Yersinia pestis, named after the French-Swiss bacteriologist Alexandre Yersin. Primarily carried by rodents and spread to humans via fleas, the disease is notorious throughout history, due to the unrivaled scale of death...

" but this only describes one of its manifestations. Other names have been used to describe this disease, such as "The Black Plague" and "The Black Death"; the latter is now used primarily to describe the second, and most devastating, pandemic of the disease.

The etymology
Etymology
Etymology is the study of the history of words, their origins, and how their form and meaning have changed over time.For languages with a long written history, etymologists make use of texts in these languages and texts about the languages to gather knowledge about how words were used during...

 of the word "plague" is believed to come from the Latin word plāga ("blow, wound") and plangere (“to strike, or to strike down”), cf. German Plage (“infestation”).

Infection and transmission



Transmission of Y. pestis to an uninfected individual is possible by any of the following means.
  • droplet contact - coughing or sneezing on another person
  • direct physical contact - touching an infected person, including sexual contact
  • indirect contact - usually by touching soil contamination
    Soil contamination
    Soil contamination or soil pollution is caused by the presence of xenobiotic chemicals or other alteration in the natural soil environment....

     or a contaminated surface
  • airborne transmission - if the microorganism can remain in the air for long periods
  • fecal-oral transmission - usually from contaminated food or water sources
  • vector borne transmission - carried by insects or other animals.


Yersinia pestis circulates in animal reservoirs, particularly in rodents, in the natural foci of infection found on all continents except Australia. The natural foci of plague are situated in a broad belt in the tropical and sub–tropical latitudes and the warmer parts of the temperate latitudes around the globe, between the parallels 55 degrees North and 40 degrees South.

Contrary to popular belief, rats did not directly start the spread of the Bubonic plague. It is mainly a disease in the flea
Flea
Flea is the common name for insects of the order Siphonaptera which are wingless insects with mouthparts adapted for piercing skin and sucking blood...

s (Xenopsylla cheopis) that infested the rats, making the rats themselves the first victims of the plague. Infection in a human occurs when a person is bitten by a flea that has been infected by biting a rodent that itself has been infected by the bite of a flea carrying the disease. The bacteria multiply inside the flea, sticking together to form a plug that blocks its stomach and causes it to starve. The flea then bites a host and continues to feed, even though it cannot quell its hunger, and consequently the flea vomits blood tainted with the bacteria back into the bite wound. The bubonic plague bacterium then infects a new victim, and the flea eventually dies from starvation. Serious outbreaks of plague are usually started by other disease outbreaks in rodents, or a rise in the rodent population.

In 1894, two bacteriologists, Alexandre Yersin of France
France
The French Republic , The French Republic , The French Republic , (commonly known as France , is a unitary semi-presidential republic in Western Europe with several overseas territories and islands located on other continents and in the Indian, Pacific, and Atlantic oceans. Metropolitan France...

 and Kitasato Shibasaburō
Kitasato Shibasaburō
Baron was a Japanese physician and bacteriologist. He is remembered as the co-discoverer of the infectious agent of bubonic plague in Hong Kong in 1894, almost simultaneously with Alexandre Yersin.-Biography:...

 of Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...

, independently isolated the bacterium in Hong Kong
Hong Kong
Hong Kong is one of two Special Administrative Regions of the People's Republic of China , the other being Macau. A city-state situated on China's south coast and enclosed by the Pearl River Delta and South China Sea, it is renowned for its expansive skyline and deep natural harbour...

 responsible for the Third Pandemic
Third Pandemic
Third Pandemic is the designation of a major Bubonic plague pandemic that began in the Yunnan province in China in 1855. This episode of bubonic plague spread to all inhabited continents, and ultimately killed more than 12 million people in India and China alone...

. 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 honor of the Pasteur Institute
Pasteur Institute
The Pasteur Institute is a French non-profit private foundation dedicated to the study of biology, micro-organisms, diseases, and vaccines. It is named after Louis Pasteur, who made some of the greatest breakthroughs in modern medicine at the time, including pasteurization and vaccines for anthrax...

, where he worked, but in 1967 it was moved to a new genus, renamed Yersinia pestis
Yersinia pestis
Yersinia pestis is a Gram-negative rod-shaped bacterium. It is a facultative anaerobe that can infect humans and other animals....

in honor 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
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...

 and India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...

 asserted that, when large numbers of rats were found dead, plague outbreaks soon followed.

In 1898, the French scientist Paul-Louis Simond
Paul-Louis Simond
Paul-Louis Simond was a French physician and biologist who was born in Beaufort-sur-Gervanne, on July 30, 1858. His major contribution to science was his demonstration that the intermediates in the transmission of bubonic plague from rats to humans are the fleas Xenopsylla cheopis that dwell on...

 (who had also come to China
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...

 to battle the Third Pandemic
Third Pandemic
Third Pandemic is the designation of a major Bubonic plague pandemic that began in the Yunnan province in China in 1855. This episode of bubonic plague spread to all inhabited continents, and ultimately killed more than 12 million people in India and China alone...

) 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
Formosa
Formosa or Ilha Formosa is a Portuguese historical name for Taiwan , literally meaning, "Beautiful Island". The term may also refer to:-Places:* Formosa Strait, another name for the Taiwan Strait...

 (Taiwan
Taiwan
Taiwan , also known, especially in the past, as Formosa , is the largest island of the same-named island group of East Asia in the western Pacific Ocean and located off the southeastern coast of mainland China. The island forms over 99% of the current territory of the Republic of China following...

), residents considered the handling of dead rats heightened the risks of 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, who had died less than 24 hours before. In a now classic experiment, Simond demonstrated how a healthy rat died of plague, after infected fleas had jumped to it, from a rat which had recently died of the plague.

Plague immunization


Since human plague is rare in most parts of the world, there is no need to vaccinate people other than those at particularly high risk of exposure. Routine vaccination is not necessary for people living in areas with enzootic plague such as the western United States. It is not indicated for most travellers to countries reporting cases, particularly if their travel is limited to urban areas with modern hotels. The CDC thus only recommends vaccination for: 1)All laboratory and field personnel who are working with Y. pestis organisms resistant to antimicrobials, 2) People engaged in aerosol experiments with Y. pestis and 3) People engaged in field operations in areas with enzootic plague where preventing exposure is not possible (such as some disaster areas).

Bubonic plague


When a flea bites a human and contaminates the wound with regurgitated blood, the plague carrying bacteria are passed into the tissue. Y. pestis can reproduce inside cells, so even if phagocytosed, they can still survive. Once in the body, the bacteria can enter the lymphatic system
Lymphatic system
The lymphoid system is the part of the immune system comprising a network of conduits called lymphatic vessels that carry a clear fluid called lymph unidirectionally toward the heart. Lymphoid tissue is found in many organs, particularly the lymph nodes, and in the lymphoid follicles associated...

, which drains interstitial fluid
Interstitial fluid
Interstitial fluid is a solution that bathes and surrounds the cells of multicellular animals. It is the main component of the extracellular fluid, which also includes plasma and transcellular fluid...

. Plague bacteria secrete several toxin
Toxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...

s, one of which is known to cause dangerous beta-adrenergic blockade
Beta blocker
Beta blockers or beta-adrenergic blocking agents, beta-adrenergic antagonists, beta-adrenoreceptor antagonists or beta antagonists, are a class of drugs used for various indications. They are particularly for the management of cardiac arrhythmias, cardioprotection after myocardial infarction ,...

.

Y. pestis spreads through the lymphatics of the infected human until it reaches a lymph node
Lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...

, where it stimulates severe haemorrhagic
Bleeding
Bleeding, technically known as hemorrhaging or haemorrhaging is the loss of blood or blood escape from the circulatory system...

 inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

 that causes the lymph nodes to expand. The expansion of lymph nodes is the cause of the characteristic "bubo" associated with the disease.

Septicemic plague



Lymphatics ultimately drain into the bloodstream, so the plague bacteria may enter the blood and travel to almost any part of the body. In septicemic plague, bacterial endotoxins cause disseminated intravascular coagulation
Disseminated intravascular coagulation
Disseminated intravascular coagulation , also known as disseminated intravascular coagulopathy or consumptive coagulopathy, is a pathological activation of coagulation mechanisms that happens in response to a variety of diseases. DIC leads to the formation of small blood clots inside the blood...

 (DIC), causing tiny clots throughout the body and possibly ischaemic necrosis (tissue death due to lack of circulation/perfusion to that tissue) from the clots. DIC results in depletion of the body's clotting resources, so that it can no longer control bleeding. Consequently, there is bleeding into the skin and other organs, which can cause red and/or black patchy rash and hemoptysis/hematemesis (coughing up/ vomiting of blood). There are bumps on the skin that look somewhat like insect bites; these are usually red, and sometimes white in the center. Untreated, septicemic plague is usually fatal. Early treatment with antibiotics reduces the mortality rate to between 4 and 15 percent. People who die from this form of plague often die on the same day symptoms first appear.

Pneumonic plague



The pneumonic
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...

 plague infects the lung
Human lung
The human lungs are the organs of respiration in humans. Humans have two lungs, with the left being divided into two lobes and the right into three lobes. Together, the lungs contain approximately of airways and 300 to 500 million alveoli, having a total surface area of about in...

s, and with that infection 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 blood (hemoptysis), or vomiting blood (hematemesis), are indistinguishable from several other respiratory illnesses. Without diagnosis and treatment, the infection can be fatal in one to six days; mortality in untreated cases is approximately 100%.

Pharyngeal plague


This is an uncommon form of plague that resembles tonsillitis
Tonsillitis
Tonsillitis is an inflammation of the tonsils most commonly caused by viral or bacterial infection. Symptoms of tonsillitis include sore throat and fever. While no treatment has been found to shorten the duration of viral tonsillitis, bacterial causes are treatable with antibiotics...

 found in cases of close contact of patients with other forms of plague.

Meningeal plague


This form of plague occurs when bacteria cross the blood brain barrier, leading to infectious meningitis.

Other clinical forms


There are a few other rare manifestations of plague, including asymptomatic plague and abortive plague. Cellulocutaneous plague sometimes results in infection of the skin and soft tissue, often around the bite site of a flea.

Treatments


Waldemar Haffkine
Waldemar Haffkine
Waldemar Mordecai Wolff Haffkine, CIE was a Russian Jewish bacteriologist, whose career was blighted in Russia because "he refused to convert to Russian Orthodoxy." He emigrated and worked at the Pasteur Institute in Paris, where he developed an anti-cholera vaccine that he tried out successfully...

, a doctor of Russian-Jewish origin who worked in Mumbai, India, was the first to invent and test a plague vaccine
Plague vaccine
Plague vaccine is a vaccine used against Yersinia pestis.-Plague immunization:A plague vaccine is used for an induction of active specific immunity in a susceptible organism to plague by means of administration an antigenic material via a variety of routes to people at risk of contracting any...

 against bubonic plague
Bubonic plague
Plague is a deadly infectious disease that is caused by the enterobacteria Yersinia pestis, named after the French-Swiss bacteriologist Alexandre Yersin. Primarily carried by rodents and spread to humans via fleas, the disease is notorious throughout history, due to the unrivaled scale of death...

, on January 10, 1897.

The traditional treatments are:
  • Streptomycin
    Streptomycin
    Streptomycin is an antibiotic drug, the first of a class of drugs called aminoglycosides to be discovered, and was the first antibiotic remedy for tuberculosis. It is derived from the actinobacterium Streptomyces griseus. Streptomycin is a bactericidal antibiotic. Streptomycin cannot be given...

     30 mg/kg IM twice daily for 7 days
  • Chloramphenicol
    Chloramphenicol
    Chloramphenicol is a bacteriostatic antimicrobial that became available in 1949. It is considered a prototypical broad-spectrum antibiotic, alongside the tetracyclines, and as it is both cheap and easy to manufacture it is frequently found as a drug of choice in the third world.Chloramphenicol is...

     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
    Gentamicin
    Gentamicin is an aminoglycoside antibiotic, used to treat many types of bacterial infections, particularly those caused by Gram-negative organisms. However, gentamicin is not used for Neisseria gonorrhoeae, Neisseria meningitidis or Legionella pneumophila...

     2.5 mg/kg IV or IM twice daily for 7 days
  • Doxycycline
    Doxycycline
    Doxycycline INN is a member of the tetracycline antibiotics group, and is commonly used to treat a variety of infections. Doxycycline is a semisynthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc. and marketed under the brand name Vibramycin. Vibramycin...

     100 mg (adults) or 2.2 mg/kg (children) orally twice daily have also been shown to be effective.

History



The earliest account describing a possible plague epidemic
Epidemic
In epidemiology, an epidemic , occurs when new cases of a certain disease, in a given human population, and during a given period, substantially exceed what is expected based on recent experience...

 is found in I Samuel 5:6 of the Hebrew Bible
Hebrew Bible
The Hebrew Bible is a term used by biblical scholars outside of Judaism to refer to the Tanakh , a canonical collection of Jewish texts, and the common textual antecedent of the several canonical editions of the Christian Old Testament...

 (Tanakh
Tanakh
The Tanakh is a name used in Judaism for the canon of the Hebrew Bible. The Tanakh is also known as the Masoretic Text or the Miqra. The name is an acronym formed from the initial Hebrew letters of the Masoretic Text's three traditional subdivisions: The Torah , Nevi'im and Ketuvim —hence...

). In this account, the Philistines
Philistines
Philistines , Pleshet or Peleset, were a people who occupied the southern coast of Canaan at the beginning of the Iron Age . According to the Bible, they ruled the five city-states of Gaza, Askelon, Ashdod, Ekron and Gath, from the Wadi Gaza in the south to the Yarqon River in the north, but with...

 of Ashdod were stricken with a plague for the crime of stealing the Ark of the Covenant
Ark of the Covenant
The Ark of the Covenant , also known as the Ark of the Testimony, is a chest described in Book of Exodus as solely containing the Tablets of Stone on which the Ten Commandments were inscribed...

 from the Children of Israel. These events have been dated to approximately the second half of the 11th century BC. The word "tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...

s" is used in most English translations
English translations of the Bible
The efforts of translating the Bible from its original languages into over 2,000 others have spanned more than two millennia. Partial translations of the Bible into languages of the English people can be traced back to the end of the 7th century, including translations into Old English and Middle...

 to describe the sores that came upon the Philistines. The Hebrew
Hebrew language
Hebrew is a Semitic language of the Afroasiatic language family. Culturally, is it considered by Jews and other religious groups as the language of the Jewish people, though other Jewish languages had originated among diaspora Jews, and the Hebrew language is also used by non-Jewish groups, such...

, however, can be interpreted as "swelling in the secret parts". The account indicates that the Philistine city and its political territory were stricken 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
Peloponnesian War
The Peloponnesian War, 431 to 404 BC, was an ancient Greek war fought by Athens and its empire against the Peloponnesian League led by Sparta. Historians have traditionally divided the war into three phases...

 (430 BC), Thucydides
Thucydides
Thucydides was a Greek historian and author from Alimos. His History of the Peloponnesian War recounts the 5th century BC war between Sparta and Athens to the year 411 BC...

 described an epidemic disease which was said to have begun in Ethiopia
Ethiopia
Ethiopia , officially known as the Federal Democratic Republic of Ethiopia, is a country located in the Horn of Africa. It is the second-most populous nation in Africa, with over 82 million inhabitants, and the tenth-largest by area, occupying 1,100,000 km2...

, passed through Egypt
Egypt
Egypt , officially the Arab Republic of Egypt, Arabic: , is a country mainly in North Africa, with the Sinai Peninsula forming a land bridge in Southwest Asia. Egypt is thus a transcontinental country, and a major power in Africa, the Mediterranean Basin, the Middle East and the Muslim world...

 and Libya
Libya
Libya is an African country in the Maghreb region of North Africa bordered by the Mediterranean Sea to the north, Egypt to the east, Sudan to the southeast, Chad and Niger to the south, and Algeria and Tunisia to the west....

, then come to the Greek world. In the Plague of Athens
Plague of Athens
The Plague of Athens was a devastating epidemic which hit the city-state of Athens in ancient Greece during the second year of the Peloponnesian War , when an Athenian victory still seemed within reach. It is believed to have entered Athens through Piraeus, the city's port and sole source of food...

, the city lost possibly one third of its population, including Pericles
Pericles
Pericles was a prominent and influential statesman, orator, and general of Athens during the city's Golden Age—specifically, the time between the Persian and Peloponnesian wars...

. Modern historians disagree on whether the plague was a critical factor in the loss of the war. Although this epidemic has long been considered an outbreak of plague, many modern scholars believe that typhus
Typhus
Epidemic typhus is a form of typhus so named because the disease often causes epidemics following wars and natural disasters...

, smallpox
Smallpox
Smallpox was an infectious disease unique to humans, caused by either of two virus variants, Variola major and Variola minor. The disease is also known by the Latin names Variola or Variola vera, which is a derivative of the Latin varius, meaning "spotted", or varus, meaning "pimple"...

, or measles
Measles
Measles, also known as rubeola or morbilli, is an infection of the respiratory system caused by a virus, specifically a paramyxovirus of the genus Morbillivirus. Morbilliviruses, like other paramyxoviruses, are enveloped, single-stranded, negative-sense RNA viruses...

 may better fit the surviving descriptions. A recent study of DNA found in the dental pulp of plague victims suggests that typhoid was actually responsible.

In the first century AD, Rufus of Ephesus
Rufus of Ephesus
Rufus of Ephesus was an ancient Greek physician and author who wrote treatises on dietetics, pathology, anatomy, and patient care. He was to some extent a follower of Hippocrates, although he at times criticized or departed from that author's teachings...

, a Greek anatomist, refers to an outbreak of plague in Libya
Libya
Libya is an African country in the Maghreb region of North Africa bordered by the Mediterranean Sea to the north, Egypt to the east, Sudan to the southeast, Chad and Niger to the south, and Algeria and Tunisia to the west....

, Egypt
Egypt
Egypt , officially the Arab Republic of Egypt, Arabic: , is a country mainly in North Africa, with the Sinai Peninsula forming a land bridge in Southwest Asia. Egypt is thus a transcontinental country, and a major power in Africa, the Mediterranean Basin, the Middle East and the Muslim world...

, and Syria
Syria
Syria , officially the Syrian Arab Republic , is a country in Western Asia, bordering Lebanon and the Mediterranean Sea to the West, Turkey to the north, Iraq to the east, Jordan to the south, and Israel to the southwest....

. 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
Alexandria
Alexandria is the second-largest city of Egypt, with a population of 4.1 million, extending about along the coast of the Mediterranean Sea in the north central part of the country; it is also the largest city lying directly on the Mediterranean coast. It is Egypt's largest seaport, serving...

 in the third century BC. If this is correct, the eastern Mediterranean world may have been familiar with bubonic plague at that early date.

First Pandemic: Plague of Justinian


The Plague of Justinian
Plague of Justinian
The Plague of Justinian was a pandemic that afflicted the Eastern Roman Empire , including its capital Constantinople, in 541–542 AD. It was one of the greatest plagues in history. The most commonly accepted cause of the pandemic is bubonic plague, which later became infamous for either causing or...

 in AD 541–542 is the first known attack on record, and marks the first firmly recorded pattern of bubonic plague. This disease is thought to have originated in China. It then spread to Africa from where the huge city of Constantinople
Constantinople
Constantinople was the capital of the Roman, Eastern Roman, Byzantine, Latin, and Ottoman Empires. Throughout most of the Middle Ages, Constantinople was Europe's largest and wealthiest city.-Names:...

 imported massive amounts of grain, mostly from Egypt, to feed its citizens. The grain ships were the source of contagion for the city, with massive public granaries nurturing the rat and flea population. At its peak the plague was killing 10,000 people in Constantinople every day and ultimately destroyed perhaps 40% of the city's inhabitants. It went on to destroy up to a quarter of the human population of the eastern Mediterranean.

In AD 588 a second major wave of plague spread through the Mediterranean into what is now France. It is estimated that the Plague of Justinian
Plague of Justinian
The Plague of Justinian was a pandemic that afflicted the Eastern Roman Empire , including its capital Constantinople, in 541–542 AD. It was one of the greatest plagues in history. The most commonly accepted cause of the pandemic is bubonic plague, which later became infamous for either causing or...

 killed as many as 100 million people across the world. It caused Europe's population
Medieval demography
This article discusses human demography in Europe during the Middle Ages, including population trends and movements. Demographic changes helped to shape and define the Middle Ages...

 to drop by around 50% between 541 and 700. It also may have contributed to the success of the Arab conquests. An outbreak of it in the AD 560s was described in AD 790 as causing "swellings in the glands...in the manner of a nut or date" in the groin "and in other rather delicate places followed by an unbearable fever". While the swellings in this description have been identified by some as buboes, there is some contention as to whether the pandemic should be attributed to the bubonic plague, Yersinia pestis, known in modern times.

Second Pandemic: Black Death


From 1347 to 1351, the Black Death
Black Death
The Black Death was one of the most devastating pandemics in human history, peaking in Europe between 1348 and 1350. Of several competing theories, the dominant explanation for the Black Death is the plague theory, which attributes the outbreak to the bacterium Yersinia pestis. Thought to have...

, a massive and deadly pandemic
Pandemic
A pandemic is an epidemic of infectious disease that is spreading through human populations across a large region; for instance multiple continents, or even worldwide. A widespread endemic disease that is stable in terms of how many people are getting sick from it is not a pandemic...

 originating in China, spread along the Silk Road
Silk Road
The Silk Road or Silk Route refers to a historical network of interlinking trade routes across the Afro-Eurasian landmass that connected East, South, and Western Asia with the Mediterranean and European world, as well as parts of North and East Africa...

 and swept through Asia, Europe and Africa. It may have reduced the world's population from 450 million to between 350 and 375 million. China
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...

 lost around half of its population, from around 123 million to around 65 million; Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...

 around 1/3 of its population, from about 75 million to about 50 million; and Africa
Africa
Africa is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area...

 approximately 1/8 of its population, from around 80 million to 70 million (mortality rates tended to be correlated with population density so Africa, being less dense overall, had the lowest death rate). This makes the Black Death the largest death toll from any known non-viral epidemic. Although accurate statistical data does not exist, it is thought that 1.4 million died in England (1/3 of England's 4.2 million people), while an even higher percentage of Italy's population was likely wiped out. On the other hand, Northeastern Germany, Bohemia, Poland and Hungary are believed to have suffered less, and there are no estimates available for Russia or the Balkans. It is conceivable that Russia may not have been as affected due to its very cold climate and large size, hence often less close contact with the contagion.

The Black Death somewhat contributed to the destruction of the feudal system in the Middle Ages, and many of the upper classes were forced to give higher wages and more freedom to their workers willing to work on the nobles' lands because of the high death toll. The Black Death also killed many great kings and nobles, leaving issues with inheritance of land and money left to their families.
In its aftermath, the Black Death may also have favoured the use of more advanced farming tools as a smaller workforce was available and plots grew larger as a result of the population loss.

The plague continued to strike parts of Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...

 sporadically until the 17th century, each time with reduced intensity and fatality, suggesting an increased resistance due to natural selection
Natural selection
Natural selection is the nonrandom process by which biologic traits become either more or less common in a population as a function of differential reproduction of their bearers. It is a key mechanism of evolution....

. Some have also argued that changes in hygiene habits and efforts to improve public health and sanitation had a significant impact on the falling rates of infection. Alternate theories which are just as well grounded in evidence include changes in rat species and rat-human ecology in Europe, to account for the rise and fall of the incidence of plague over the centuries.

Nature of the disease


In the early 20th century, following the identification by Yersin and Kitasato of the plague bacterium that caused the late 19th and early 20th century Asian bubonic plague (the Third Pandemic
Third Pandemic
Third Pandemic is the designation of a major Bubonic plague pandemic that began in the Yunnan province in China in 1855. This episode of bubonic plague spread to all inhabited continents, and ultimately killed more than 12 million people in India and China alone...

), most scientists and historians came to believe that the Black Death was an incidence of this 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. It was claimed that the disease was spread mainly by black rat
Black Rat
The black rat is a common long-tailed rodent of the genus Rattus in the subfamily Murinae . The species originated in tropical Asia and spread through the Near East in Roman times before reaching Europe by the 1st century and spreading with Europeans across the world.-Taxonomy:The black rat was...

s in Asia and that therefore there must have been black rats in north-west Europe at the time of the Black Death to spread it, although black rats are currently rare except near the Mediterranean. This led to the development of a theory that brown rat
Brown Rat
The brown rat, common rat, sewer rat, Hanover rat, Norway rat, Brown Norway rat, Norwegian rat, or wharf rat is one of the best known and most common rats....

s had invaded Europe, largely wiping out black rats, bringing the plagues to an end, although there is no evidence for the theory in historical records. Some historians suggest that marmot
Marmot
The marmots are a genus, Marmota, of squirrels. There are 14 species in this genus.Marmots are generally large ground squirrels. Those most often referred to as marmots tend to live in mountainous areas such as the Alps, northern Apennines, Eurasian steppes, Carpathians, Tatras, and Pyrenees in...

s, rather than rat
Rat
Rats are various medium-sized, long-tailed rodents of the superfamily Muroidea. "True rats" are members of the genus Rattus, the most important of which to humans are the black rat, Rattus rattus, and the brown rat, Rattus norvegicus...

s, were the primary carriers of the disease.

The view that the Black Death was caused by Yersinia pestis has been incorporated into medical textbooks throughout the 20th century and has become part of popular culture, as illustrated by recent books, such as John Kelly's The Great Mortality. Many modern 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. According to the accounts of the time the black death was extremely virulent, unlike the 19th and early 20th century bubonic plague. Samuel K. Cohn has made a comprehensive attempt to rebut the bubonic plague theory. In the Encyclopedia of Population, he points to five major weaknesses in this theory:
  • very different transmission speeds — the Black Death was reported to have spread 385 km in 91 days (4.23 km/day) in 664, compared to 12–15 km a year for the modern Bubonic Plague, with the assistance of trains and cars
  • difficulties with the attempt to explain the rapid spread of the Black Death by arguing that it was spread by the rare pneumonic form of the disease — in fact this form killed less than 0.3% of the infected population in its worst outbreak (Manchuria
    Manchuria
    Manchuria is a historical name given to a large geographic region in northeast Asia. Depending on the definition of its extent, Manchuria usually falls entirely within the People's Republic of China, or is sometimes divided between China and Russia. The region is commonly referred to as Northeast...

     in 1911)
  • different seasonality — the modern plague can only be sustained at temperatures between 10 and 26°C and requires high humidity, while the Black Death occurred even in Norway
    Norway
    Norway , officially the Kingdom of Norway, is a Nordic unitary constitutional monarchy whose territory comprises the western portion of the Scandinavian Peninsula, Jan Mayen, and the Arctic archipelago of Svalbard and Bouvet Island. Norway has a total area of and a population of about 4.9 million...

     in the middle of the winter and in the Mediterranean in the middle of hot dry summers
  • very different death rates — in several places (including Florence
    Florence
    Florence is the capital city of the Italian region of Tuscany and of the province of Florence. It is the most populous city in Tuscany, with approximately 370,000 inhabitants, expanding to over 1.5 million in the metropolitan area....

     in 1348) over 75% of the population appears to have died; in contrast the highest mortality for the modern Bubonic Plague was 3% in Mumbai
    Mumbai
    Mumbai , formerly known as Bombay in English, is the capital of the Indian state of Maharashtra. It is the most populous city in India, and the fourth most populous city in the world, with a total metropolitan area population of approximately 20.5 million...

     in 1903
  • the cycles and trends of infection were very different between the diseases — humans did not develop resistance to the modern disease, but resistance to the Black Death rose sharply, so that eventually it became mainly a childhood disease

Cohn also points out that while the identification of the disease as having buboes relies on accounts of Boccaccio
Giovanni Boccaccio
Giovanni Boccaccio was an Italian author and poet, a friend, student, and correspondent of Petrarch, an important Renaissance humanist and the author of a number of notable works including the Decameron, On Famous Women, and his poetry in the Italian vernacular...

 and others, they described buboes, abscess
Abscess
An abscess is a collection of pus that has accumulated in a cavity formed by the tissue in which the pus resides due to an infectious process or other foreign materials...

es, rash
Rash
A rash is a change of the skin which affects its color, appearance or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked or blistered, swell and may be painful. The causes, and...

es and carbuncle
Carbuncle
A carbuncle is an abscess larger than a boil, usually with one or more openings draining pus onto the skin. It is usually caused by bacterial infection, most commonly Staphylococcus aureus. The infection is contagious and may spread to other areas of the body or other people...

s occurring all over the body, the neck or behind the ears. In contrast, the modern disease rarely has more than one bubo, most commonly in the groin, and is not characterised by abscesses, rashes and carbuncles.

Researchers have offered a mathematical model based on the changing demography of Europe from 1000 to 1800 AD demonstrating how plague epidemics, 1347 to 1670, could have provided the selection pressure that raised the frequency of a mutation to the level seen today that prevent HIV from entering macrophages that carry the mutation (the average frequency of this allele
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...

 is 10% in European populations). It is suggested that the original single mutation appeared over 2,500 years ago and that persistent epidemics of a haemorrhagic fever struck at the early classical civilizations.

However recent research published in the open-access scientific journal PloS Pathogens in October 2010 presented conclusive evidence that two previously unknown clade
Clade
A clade is a group consisting of a species and all its descendants. In the terms of biological systematics, a clade is a single "branch" on the "tree of life". The idea that such a "natural group" of organisms should be grouped together and given a taxonomic name is central to biological...

s (variant strains) of Y. pestis were responsible for the Black Death. A multinational team conducted new surveys that used both ancient DNA analyses and protein-specific detection to find DNA and protein signatures specific for Y. pestis in human skeletons from widely distributed mass graves in northern, central and southern Europe that were associated archaeologically with the Black Death and subsequent resurgences. The authors concluded that this research, together with prior analyses from the south of France and Germany,
"...ends the debate about the etiology of the Black Death, and unambiguously demonstrates that Y. pestis was the causative agent of the epidemic plague that devastated Europe during the Middle Ages."


The study also identified two previously unknown but related strains of Y. pestis that were associated with distinct medieval mass graves. These were found to be ancestral to modern isolates of the present-day Y. pestis strains 'Orientalis' and 'Medievalis', suggesting that these variant strains (which are now presumed to be extinct) may have entered Europe in two waves. Surveys of plague pit remains in France and England indicate that the first variant entered Europe through the port of Marseille
Marseille
Marseille , known in antiquity as Massalia , is the second largest city in France, after Paris, with a population of 852,395 within its administrative limits on a land area of . The urban area of Marseille extends beyond the city limits with a population of over 1,420,000 on an area of...

 around November 1347 and spread through France over the next two years, eventually reaching England in the spring of 1349, where it spread through the country in three successive epidemics.

However, surveys of plague pit remains from the Netherlands town of Bergen op Zoom
Bergen op Zoom
Bergen op Zoom is a municipality and a city located in the south of the Netherlands.-History:Bergen op Zoom was granted city status probably in 1266. In 1287 the city and its surroundings became a lordship as it was separated from the lordship of Breda. The lordship was elevated to a margraviate...

 showed evidence of a second Y. pestis genotype which differed from that found in Britain and France and this second strain is now thought to have been responsible for the pandemic that spread through the Low Countries from 1350. This discovery implies that Bergen op Zoom (and possibly other parts of the southern Netherlands) was not directly infected from England or France c. AD 1349, and the researchers have suggested that a second wave of plague infection, distinct from that which occurred in Britain and France, may have been carried to the Low Countries from Norway, the Hanseatic
Hanseatic League
The Hanseatic League was an economic alliance of trading cities and their merchant guilds that dominated trade along the coast of Northern Europe...

 cities, or another site.

Third Pandemic


The Third Pandemic
Third Pandemic
Third Pandemic is the designation of a major Bubonic plague pandemic that began in the Yunnan province in China in 1855. This episode of bubonic plague spread to all inhabited continents, and ultimately killed more than 12 million people in India and China alone...

 began in China's Yunnan province in 1855, spreading plague to all inhabited continents and ultimately killing more than 12 million people in India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...

 and China alone. Casualty patterns indicate that waves of this pandemic may have come from two different sources. The first was primarily bubo
Bubo
Bubo may refer to:* A bubo, a rounded swelling on the skin of a person afflicted by the bubonic plague.* Bubo, the horned owl and eagle-owl genus.* Bubo, a mechanical owl in the 1981 film Clash of the Titans...

nic and was carried around the world through ocean-going trade, transporting infected persons, rats, and cargoes harboring fleas. The second, more virulent strain was primarily pneumonic
Pneumonic device
A pneumonic device is any equipment designed for use with or relating to the lungs. The iron lung and medical ventilator may be considered pneumonic devices. The term may also refer to any device used in the field of respiratory therapy....

 in character, with a strong person-to-person contagion. This strain was largely confined to Manchuria
Manchuria
Manchuria is a historical name given to a large geographic region in northeast Asia. Depending on the definition of its extent, Manchuria usually falls entirely within the People's Republic of China, or is sometimes divided between China and Russia. The region is commonly referred to as Northeast...

 and Mongolia
Mongolia
Mongolia is a landlocked country in East and Central Asia. It is bordered by Russia to the north and China to the south, east and west. Although Mongolia does not share a border with Kazakhstan, its western-most point is only from Kazakhstan's eastern tip. Ulan Bator, the capital and largest...

. Researchers during the "Third Pandemic" identified plague vectors and the plague bacterium (see above), leading in time to modern treatment methods.

Plague occurred in Russia
Russia
Russia or , officially known as both Russia and the Russian Federation , is a country in northern Eurasia. It is a federal semi-presidential republic, comprising 83 federal subjects...

 in 1877–1889 in rural areas near the Ural Mountains
Ural Mountains
The Ural Mountains , or simply the Urals, are a mountain range that runs approximately from north to south through western Russia, from the coast of the Arctic Ocean to the Ural River and northwestern Kazakhstan. Their eastern side is usually considered the natural boundary between Europe and Asia...

 and the Caspian Sea
Caspian Sea
The Caspian Sea is the largest enclosed body of water on Earth by area, variously classed as the world's largest lake or a full-fledged sea. The sea has a surface area of and a volume of...

. 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
Bobak Marmot
The bobak marmot , also known as the steppe marmot, is a species of marmot that inhabits the steppes of Eastern Europe and Central Asia. It is also found in Belarus...

, a small rodent considered a very dangerous plague reservoir. The last significant Russian outbreak of Plague was in Siberia
Siberia
Siberia is an extensive region constituting almost all of Northern Asia. Comprising the central and eastern portion of the Russian Federation, it was part of the Soviet Union from its beginning, as its predecessor states, the Tsardom of Russia and the Russian Empire, conquered it during the 16th...

 in 1910 after sudden demand for Marmot skins (a substitute for Sable
Sable
The sable is a species of marten which inhabits forest environments, primarily in Russia from the Ural Mountains throughout Siberia, in northern Mongolia and China and on Hokkaidō in Japan. Its range in the wild originally extended through European Russia to Poland and Scandinavia...

) increased the price by 400 percent. The traditional hunters would not hunt a sick Marmot and it was taboo to eat the fat from under the arm (the axillary lymphatic gland
Lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...

 that often harboured the plague) so outbreaks tended to be confined to single individuals. The price increase, however, attracted thousands of Chinese
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...

 hunters from Manchuria
Manchuria
Manchuria is a historical name given to a large geographic region in northeast Asia. Depending on the definition of its extent, Manchuria usually falls entirely within the People's Republic of China, or is sometimes divided between China and Russia. The region is commonly referred to as Northeast...

 who not only caught the sick animals but also ate the fat, which was considered a delicacy. The plague spread from the hunting grounds to the terminus of the Chinese Eastern Railway
Chinese Eastern Railway
The Chinese Eastern Railway or was a railway in northeastern China . It connected Chita and the Russian Far East. English-speakers have sometimes referred to this line as the Manchurian Railway...

 and then followed the track for 2,700 km. The plague lasted 7 months and killed 60,000 people.

The bubonic plague continued to circulate through different ports globally for the next fifty years; however, it was primarily found in Southeast Asia. An epidemic in Hong Kong
Hong Kong
Hong Kong is one of two Special Administrative Regions of the People's Republic of China , the other being Macau. A city-state situated on China's south coast and enclosed by the Pearl River Delta and South China Sea, it is renowned for its expansive skyline and deep natural harbour...

 in 1894 had particularly high death rates, 90%. As late as 1897, medical authorities in the European powers organized a conference in Venice
Venice
Venice is a city in northern Italy which is renowned for the beauty of its setting, its architecture and its artworks. It is the capital of the Veneto region...

, seeking ways to keep the plague out of Europe. Mumbai plague epidemic
Mumbai plague epidemic
The Mumbai plague epidemic was a bubonic plague epidemic that stuck the city of Mumbai in the late nineteenth century. The plague killed thousands, and many fled the city leading to a drastic fall in the population of the city.-Causes:...

 struck the city of Mumbai
Mumbai
Mumbai , formerly known as Bombay in English, is the capital of the Indian state of Maharashtra. It is the most populous city in India, and the fourth most populous city in the world, with a total metropolitan area population of approximately 20.5 million...

 (Bombay) in 1896. The disease reached the Republic of Hawaii
Republic of Hawaii
The Republic of Hawaii was the formal name of the government that controlled Hawaii from 1894 to 1898 when it was run as a republic. The republic period occurred between the administration of the Provisional Government of Hawaii which ended on July 4, 1894 and the adoption of the Newlands...

 in December 1899, and the Board of Health’s decision to initiate controlled burns of select buildings in Honolulu’s Chinatown
Chinatown
A Chinatown is an ethnic enclave of overseas Chinese people, although it is often generalized to include various Southeast Asian people. Chinatowns exist throughout the world, including East Asia, Southeast Asia, the Americas, Australasia, and Europe. Binondo's Chinatown located in Manila,...

 turned into an uncontrolled fire which led to the inadvertent burning of most of Chinatown on January 20, 1900 according to the Star Bulletin's Feature on the Great Chinatown Fire. Plague finally reached the United States later that year in San Francisco, and persisted in Hawaii on the outer islands of Maui and Hawaii (The Big Island) until it was finally eradicated in 1959.

Although the outbreak that began in China
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...

 in 1855 is conventionally known as the Third Pandemic
Third Pandemic
Third Pandemic is the designation of a major Bubonic plague pandemic that began in the Yunnan province in China in 1855. This episode of bubonic plague spread to all inhabited continents, and ultimately killed more than 12 million people in India and China alone...

, (see above), 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.

Research done by a team of biologists from the Institute of Pasteur in Paris and Johannes Gutenberg University Mainz in Germany by analyzing the DNA and proteins from plague pits was published in Oct., 2010, reported beyond doubt that all 'the three major plagues' were due to at least two previously unknown strains of Yersinia pestis and originated from China. A team of medical geneticists led by Mark Achtman of University College Cork in Ireland reconstructed a family tree of the bacterium and concluded in an online issue of Nature Genetics published on 31 Oct., 2010 that all three of the great waves of plague originated from China. Europe’s Plagues Came From China, Study Finds.

Plague as a biological weapon


Plague has a long history as a biological weapon. Historical accounts from ancient China and medieval Europe detail the use of infected animal carcasses, such as cows or horses, and human carcasses, by the Xiongnu
Xiongnu
The Xiongnu were ancient nomadic-based people that formed a state or confederation north of the agriculture-based empire of the Han Dynasty. Most of the information on the Xiongnu comes from Chinese sources...

/Huns
Huns
The Huns were a group of nomadic people who, appearing from east of the Volga River, migrated into Europe c. AD 370 and established the vast Hunnic Empire there. Since de Guignes linked them with the Xiongnu, who had been northern neighbours of China 300 years prior to the emergence of the Huns,...

, Mongols
Mongols
Mongols ) are a Central-East Asian ethnic group that lives mainly in the countries of Mongolia, China, and Russia. In China, ethnic Mongols can be found mainly in the central north region of China such as Inner Mongolia...

, Turks
Turkic peoples
The Turkic peoples are peoples residing in northern, central and western Asia, southern Siberia and northwestern China and parts of eastern Europe. They speak languages belonging to the Turkic language family. They share, to varying degrees, certain cultural traits and historical backgrounds...

, and other groups, to contaminate enemy water supplies. Han Dynasty
Han Dynasty
The Han Dynasty was the second imperial dynasty of China, preceded by the Qin Dynasty and succeeded by the Three Kingdoms . It was founded by the rebel leader Liu Bang, known posthumously as Emperor Gaozu of Han. It was briefly interrupted by the Xin Dynasty of the former regent Wang Mang...

 General Huo Qubing
Huo Qubing
Huo Qubing , born in Linfen, Shanxi, was a general of the western Han dynasty under Emperor Wu. Being the illegitimate son of Wei Shaoer, he was the nephew of Wei Qing and Empress Wei Zifu....

 is recorded to have died of such a contamination while engaging in warfare against the Xiongnu. Plague victims were also reported to have been tossed by catapult
Catapult
A catapult is a device used to throw or hurl a projectile a great distance without the aid of explosive devices—particularly various types of ancient and medieval siege engines. Although the catapult has been used since ancient times, it has proven to be one of the most effective mechanisms during...

 into cities under siege.

In 1347, the Genoese
Republic of Genoa
The Most Serene Republic of Genoa |Ligurian]]: Repúbrica de Zêna) was an independent state from 1005 to 1797 in Liguria on the northwestern Italian coast, as well as Corsica from 1347 to 1768, and numerous other territories throughout the Mediterranean....

 possession of Caffa
Theodosia
Feodosiya is a port and resort city in Crimea, Ukraine, on the Black Sea coast. During much of its history the town was known as Caffa or Kaffa .- History :...

, a great trade emporium on the Crimea
Crimea
Crimea , or the Autonomous Republic of Crimea , is a sub-national unit, an autonomous republic, of Ukraine. It is located on the northern coast of the Black Sea, occupying a peninsula of the same name...

n peninsula, came under siege by an army of Mongol warriors of the Golden Horde
Golden Horde
The Golden Horde was a Mongol and later Turkicized khanate that formed the north-western sector of the Mongol Empire...

 under the command of Janibeg. After a protracted siege during which the Mongol army was reportedly withering from the disease, they decided to use the infected corpses as a biological weapon. The corpses were catapulted over the city walls, infecting the inhabitants. The Genoese traders fled, transferring the plague (Black Death
Black Death
The Black Death was one of the most devastating pandemics in human history, peaking in Europe between 1348 and 1350. Of several competing theories, the dominant explanation for the Black Death is the plague theory, which attributes the outbreak to the bacterium Yersinia pestis. Thought to have...

) via their ships into the south of Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...

, whence it rapidly spread.

During World War II
World War II
World War II, or the Second World War , was a global conflict lasting from 1939 to 1945, involving most of the world's nations—including all of the great powers—eventually forming two opposing military alliances: the Allies and the Axis...

, the Japanese Army
Imperial Japanese Army
-Foundation:During the Meiji Restoration, the military forces loyal to the Emperor were samurai drawn primarily from the loyalist feudal domains of Satsuma and Chōshū...

 developed weaponised plague, based on the breeding and release of large numbers of fleas. During the Japanese occupation of Manchuria
Manchuria
Manchuria is a historical name given to a large geographic region in northeast Asia. Depending on the definition of its extent, Manchuria usually falls entirely within the People's Republic of China, or is sometimes divided between China and Russia. The region is commonly referred to as Northeast...

, Unit 731
Unit 731
was a covert biological and chemical warfare research and development unit of the Imperial Japanese Army that undertook lethal human experimentation during the Second Sino-Japanese War and World War II. It was responsible for some of the most notorious war crimes carried out by Japanese...

 deliberately infected Chinese
Chinese people
The term Chinese people may refer to any of the following:*People with Han Chinese ethnicity ....

, Korean, and Manchurian civilian
Civilian
A civilian under international humanitarian law is a person who is not a member of his or her country's armed forces or other militia. Civilians are distinct from combatants. They are afforded a degree of legal protection from the effects of war and military occupation...

s and prisoners of war
Prisoner of war
A prisoner of war or enemy prisoner of war is a person, whether civilian or combatant, who is held in custody by an enemy power during or immediately after an armed conflict...

 with the plague bacterium. These subjects, termed "maruta", or "logs", were then studied by dissection
Dissection
Dissection is usually the process of disassembling and observing something to determine its internal structure and as an aid to discerning the functions and relationships of its components....

, others by vivisection while still conscious. Members of the unit such as Shiro Ishii
Shiro Ishii
was a Japanese microbiologist and the lieutenant general of Unit 731, a biological warfare unit of the Imperial Japanese Army responsible for human experimentation and war crimes during the Second Sino-Japanese War.-Early years:...

 were exonerated from the Tokyo tribunal by Douglas MacArthur
Douglas MacArthur
General of the Army Douglas MacArthur was an American general and field marshal of the Philippine Army. He was a Chief of Staff of the United States Army during the 1930s and played a prominent role in the Pacific theater during World War II. He received the Medal of Honor for his service in the...

 but 12 of them were prosecuted in the Khabarovsk War Crime Trials
Khabarovsk War Crime Trials
Khabarovsk War Crime Trials were a series of hearings held between December 25 - 31st, 1949 in the Soviet Union's industrial city of Khabarovsk situated on the Russian Far East...

 in 1949 during which some admitted having spread Bubonic plague
Bubonic plague
Plague is a deadly infectious disease that is caused by the enterobacteria Yersinia pestis, named after the French-Swiss bacteriologist Alexandre Yersin. Primarily carried by rodents and spread to humans via fleas, the disease is notorious throughout history, due to the unrivaled scale of death...

 within a 36-km radius around the city of Changde
Battle of Changde
- Sources :* Hsu Long-hsuen and Chang Ming-kai, History of The Sino-Japanese War 2nd Ed., 1971. Translated by Wen Ha-hsiung, Chung Wu Publishing; 33, 140th Lane, Tung-hwa Street, Taipei, Taiwan Republic of China. Pg...

.

Ishii innovated bombs containing live mice and fleas, with very small explosive loads, to deliver the weaponized microbes, overcoming the problem of the explosive killing the infected animal and insect by the use of a ceramic, rather than metal, casing for the warhead. While no records survive of the actual usage of the ceramic shells, prototypes exist and are believed to have been used in experiments during WWII.

After World War II, both the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

 and the Soviet Union
Soviet Union
The Soviet Union , officially the Union of Soviet Socialist Republics , was a constitutionally socialist state that existed in Eurasia between 1922 and 1991....

 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
Diphtheria
Diphtheria is an upper respiratory tract illness caused by Corynebacterium diphtheriae, a facultative anaerobic, Gram-positive bacterium. It is characterized by sore throat, low fever, and an adherent membrane on the tonsils, pharynx, and/or nasal cavity...

), and genetic engineering. Scientists who worked in USSR
Soviet Union
The Soviet Union , officially the Union of Soviet Socialist Republics , was a constitutionally socialist state that existed in Eurasia between 1922 and 1991....

 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. The plague can be easily treated with antibiotics, thus a widespread epidemic
Epidemic
In epidemiology, an epidemic , occurs when new cases of a certain disease, in a given human population, and during a given period, substantially exceed what is expected based on recent experience...

 is highly unlikely in developed countries.


1994 epidemic in Surat, India



In 1994, there was a pneumonic plague epidemic in Surat
Surat
Surat , also known as Suryapur, is the commercial capital city of the Indian state of Gujarat. Surat is India's Eighth most populous city and Ninth-most populous urban agglomeration. It is also administrative capital of Surat district and one of the fastest growing cities in India. The city proper...

, India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...

 that resulted in 52 deaths and in a large internal migration of about 300,000 residents, who fled fearing quarantine.

A combination of heavy monsoon rain and clogged sewers led to massive flooding which resulted in unhygienic conditions and a number of uncleared animal carcasses. It is believed that this situation precipitated the epidemic. There was widespread fear that the flood of refugees might spread the epidemic to other parts of India and the world, but that scenario was averted, probably as a result of effective public health response mounted by the Indian health authorities.

Much like the Black Death
Black Death
The Black Death was one of the most devastating pandemics in human history, peaking in Europe between 1348 and 1350. Of several competing theories, the dominant explanation for the Black Death is the plague theory, which attributes the outbreak to the bacterium Yersinia pestis. Thought to have...

 that spread through medieval Europe, some questions still remain unanswered about the 1994 epidemic in Surat.

Initial questions about whether it was an epidemic of plague arose because the Indian health authorities were unable to culture Yersinia pestis, but this could have been due to poor laboratory procedures. Yet, there are several lines of evidence strongly suggesting that it was a plague epidemic: blood tests for Yersinia were positive, a number of individuals showed antibodies against Yersinia and the clinical symptoms displayed by the affected were all consistent with the disease being plague.

Other contemporary cases



  • On August 31, 1984, the Centers for Disease Control and Prevention
    Centers for Disease Control and Prevention
    The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...

     reported a case of pneumonic
    Pneumonia
    Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...

     plague in Claremont, California
    Claremont, California
    Claremont is a small affluent college town in eastern Los Angeles County, California, United States, about east of downtown Los Angeles at the base of the San Gabriel Mountains. The population as of the 2010 census is 34,926. Claremont is known for its seven higher-education institutions, its...

    . The CDC believes that the patient, a veterinarian
    Veterinarian
    A veterinary physician, colloquially called a vet, shortened from veterinarian or veterinary surgeon , is a professional who treats disease, disorder and injury in animals....

    , contracted plague from a stray cat. As the cat wasn't available for necropsy, this could not be ultimately confirmed.
  • From 1995 to 1998, annual outbreaks of plague were witnessed in Mahajanga
    Mahajanga
    Mahajanga is a city and a district on the north-west coast of Madagascar.- City :The City of Mahajanga is the capital of the Boeny region. Population: 135,660 ....

    , Madagascar.
  • In the U.S., about half of all fatal cases of plague since 1970 have occurred in New Mexico
    New Mexico
    New Mexico is a state located in the southwest and western regions of the United States. New Mexico is also usually considered one of the Mountain States. With a population density of 16 per square mile, New Mexico is the sixth-most sparsely inhabited U.S...

    . There were 2 plague deaths in the state in 2006, the first fatalities in 12 years.
  • In February 2002, a small outbreak of pneumonic plague took place in the Shimla District
    Shimla district
    Shimla district of Himachal Pradesh, lies between the longitude 77.00" and 78.19" east and latitude 30.45" and 31.44" north, has its headquarters at Shimla city. It is surrounded by Mandi and Kullu in the north, Kinnaur in the east, Uttarakhand in the south, Sirmaur in the west...

     of Himachal Pradesh
    Himachal Pradesh
    Himachal Pradesh is a state in Northern India. It is spread over , and is bordered by the Indian states of Jammu and Kashmir on the north, Punjab on the west and south-west, Haryana and Uttar Pradesh on the south, Uttarakhand on the south-east and by the Tibet Autonomous Region on the east...

     state in northern India
    India
    India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...

    .
  • In Fall of 2002, a New Mexico couple contracted the disease, just prior to a visit to New York City. They both were treated by antibiotics, but the male required amputation of both feet to fully recover, due to the lack of blood flow to his feet, cut off by the bacteria.
  • On April 19, 2006, CNN News and others reported a case of plague in Los Angeles
    Los Ángeles
    Los Ángeles is the capital of the province of Biobío, in the commune of the same name, in Region VIII , in the center-south of Chile. It is located between the Laja and Biobío rivers. The population is 123,445 inhabitants...

    , California
    California
    California is a state located on the West Coast of the United States. It is by far the most populous U.S. state, and the third-largest by land area...

    , lab technician Nirvana Kowlessar, the first reported case in that city since 1984.
  • In May 2006, KSL Newsradio
    KSL Newsradio
    KSL NewsRadio is a radio programming service based in Salt Lake City, Utah. It is broadcast simultaneously on AM station KSL and FM station KSL-FM...

     reported a case of plague found in dead field mice and chipmunks at Natural Bridges National Monument
    Natural Bridges National Monument
    Natural Bridges National Monument is a U.S. National Monument located about north west of the Four Corners boundary of southeast Utah, in the western United States, at the junction of White Canyon and Armstrong Canyon, part of the Colorado River drainage...

     about 40 miles (64 km) west of Blanding
    Blanding, Utah
    Blanding is a city in San Juan County, Utah, United States. The population was 3,162 at the 2000 census, making it the most populated city in San Juan County. It was settled in the late 19th century by Mormon settlers, predominantly from the famed Hole-In-The-Rock expedition...

     in San Juan County
    San Juan County, Utah
    As of the current census of 2010, there were 14,746 people and 4,505 households. The racial and ethnic composition of the population was 50.4% Native American, 45.8% white, 0.3% Asian, 0.2% African American and 2.3% reporting two or more races...

    , Utah
    Utah
    Utah is a state in the Western United States. It was the 45th state to join the Union, on January 4, 1896. Approximately 80% of Utah's 2,763,885 people live along the Wasatch Front, centering on Salt Lake City. This leaves vast expanses of the state nearly uninhabited, making the population the...

    .
  • In May 2006, Arizona media reported a case of plague found in a cat.
  • One hundred deaths resulting from pneumonic plague were reported in Ituri
    Ituri
    Ituri may refer to:* Ituri Interim Administration, an interim administration in the northeastern Democratic Republic of the Congo* Ituri Province, a proposed province in the northeastern Democratic Republic of the Congo* Ituri Rainforest* Ituri River...

     district of the eastern Democratic Republic of the Congo
    Democratic Republic of the Congo
    The Democratic Republic of the Congo is a state located in Central Africa. It is the second largest country in Africa by area and the eleventh largest in the world...

     in June 2006. Control of the plague was proving difficult due to the ongoing conflict
    Ituri Conflict
    The Ituri conflict is a conflict between the agriculturalist Lendu and pastoralist Hema ethnic groups in the Ituri region of the northeastern Democratic Republic of Congo . While there have been many phases to the conflict, the most recent armed clashes ran from 1999 to 2003, with a low-level...

    .
  • It was reported in September 2006 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
    University of Medicine and Dentistry of New Jersey
    The University of Medicine and Dentistry of New Jersey is the state-run health sciences institution of New Jersey, United States. It has eight distinct academic units...

    , which conducts anti-bioterrorism
    Bioterrorism
    Bioterrorism is terrorism involving the intentional release or dissemination of biological agents. These agents are bacteria, viruses, or toxins, and may be in a naturally occurring or a human-modified form. For the use of this method in warfare, see biological warfare.-Definition:According to the...

     research for the United States
    United States
    The United States of America is a federal constitutional republic comprising fifty states and a federal district...

     government.
  • On May 16, 2007, an 8-year-old hooded capuchin monkey
    Capuchin monkey
    The capuchins are New World monkeys of the genus Cebus. The range of capuchin monkeys includes Central America and South America as far south as northern Argentina...

     in the Denver Zoo
    Denver Zoo
    The Denver Zoo is an facility located in City Park of Denver, Colorado, USA. Founded in 1896, it is owned by the City and County of Denver and funded in part by the Scientific and Cultural Facilities District . It was the most popular paid attraction in the Denver metropolitan area in 2005.The...

     died of the bubonic plague. Five squirrels and a rabbit were also found dead on zoo grounds and tested positive for the disease.
  • On June 5, 2007 in Torrance County, New Mexico a 58 year old woman developed bubonic plague, which progressed to pneumonic
    Pneumonia
    Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...

     plague.
  • On November 2, 2007, Eric York, a 37 year old wildlife biologist for the National Park Service's and The Felidae Conservation Fund, was found dead in his home at Grand Canyon National Park
    Grand Canyon National Park
    Grand Canyon National Park is the United States' 15th oldest national park and is located in Arizona. Within the park lies the Grand Canyon, a gorge of the Colorado River, considered to be one of the Wonders of the World. The park covers of unincorporated area in Coconino and Mohave counties.Most...

    . On October 27, York performed a necropsy on a mountain lion that had likely perished from the disease and three days afterward York complained of flu-like symptoms and called in sick from work. He was treated at a local clinic but was not diagnosed with any serious ailment. The discovery of his death sparked a minor health scare, with officials stating he likely died of either plague or hantavirus
    Hantavirus
    Hantaviruses are negative sense RNA viruses in the Bunyaviridae family. Humans may be infected with hantaviruses through rodent bites, urine, saliva or contact with rodent waste products...

    , and 49 people who had come in to contact with York were given aggressive antibiotic treatments. None of them fell ill. Autopsy results released on November 9, confirmed the presence of Y. pestis in his body, confirming plague as a likely cause of death.
  • In January 2008, at least 18 people died of bubonic plague in Madagascar.
  • On June 16, 2009, Libyan authorities have reported an outbreak of bubonic plague in Tobruk
    Tobruk
    Tobruk or Tubruq is a city, seaport, and peninsula on Libya's eastern Mediterranean coast, near the border with Egypt. It is the capital of the Butnan District and has a population of 120,000 ....

    , Libya
    Libya
    Libya is an African country in the Maghreb region of North Africa bordered by the Mediterranean Sea to the north, Egypt to the east, Sudan to the southeast, Chad and Niger to the south, and Algeria and Tunisia to the west....

    . 16-18 cases were reported, including one death.
  • On August 2, 2009, Chinese authorities quarantined the town of Ziketan, Xinghai County
    Xinghai County
    Xinghai County is county under the jurisdiction of Hainan Tibetan Autonomous Prefecture, Qinghai Province, People's Republic of ChinaXinghai has an area of 13,158 square kilometers, and a 2001 population of 60,000....

     in Hainan Tibetan Autonomous Prefecture
    Hainan Tibetan Autonomous Prefecture
    Hainan Tibetan Autonomous Prefecture is an autonomous prefecture of northeastern Qinghai Province in Western China. The prefecture has an area of and its seat is located in Gonghe County...

    , Qinghai
    Qinghai
    Qinghai ; Oirat Mongolian: ; ; Salar:) is a province of the People's Republic of China, named after Qinghai Lake...

     Province (Northwestern China) after an outbreak of pneumonic plague
    Pneumonic plague
    Pneumonic plague, a severe type of lung infection, is one of three main forms of plague, all of which are caused by the bacterium Yersinia pestis. It is more virulent and rare than bubonic plague...

    . As of this writing, three have died and ten more are ill, being treated in hospital.
  • On September 13, 2009, Dr. Malcolm Casadaban
    Malcolm Casadaban
    Malcolm Casadaban was Associate Professor of Molecular Genetics and Cell Biology and of Microbiology at the University of Chicago...

     died following an accidental laboratory exposure to an attenuated strain of the plague bacterium. This has happened due to his undiagnosed hereditary hemochromatosis (iron overload). He was an Associate Professor of Molecular Genetics and Cell Biology and of Microbiology at the University of Chicago.
  • On 1 July 2010, 8 cases of Bubonic plague have been reported in humans in the District of Chicama, Peru. One 32 year old man has been affected, as well as 3 boys and 4 girls ranging in age from 8 to 14 years old. 425 houses have been fumigated and 1210 guinea pigs, 232 dogs, 128 cats and 73 rabbits have been given anti flea treatment in an effort to stop the epidemic.

External links