Plague (disease)

Plague is an infectious disease caused by the bacterium Yersinia pestis.[2] Symptoms include fever, weakness and headache.[1] Usually this begins one to seven days after exposure.[2] In the bubonic form there is also swelling of lymph nodes, while in the septicemic form tissues may turn black and die, and in the pneumonic form shortness of breath, cough and chest pain may occur.[1]

Bubonic and septicemic plague is generally spread by flea bites or handling an infected animal.[1] The pneumonitic form is generally spread between people through the air via infectious droplets.[1] Diagnosis is typically by finding the bacterium in fluid from a lymph node, blood or sputum.[2]

Those at high risk may be vaccinated.[2] Those exposed to a case of pneumonic plague may be treated with preventative medication.[2] If infected, treatment is with antibiotics and supportive care.[2] Typically antibiotics include a combination of gentamicin and a fluoroquinolone.[3] The risk of death with treatment is about 10% while without it is about 70%.[4]

Globally about 600 cases are reported a year.[2] In 2017 the countries with the most cases include the Democratic Republic of the Congo, Madagascar and Peru.[2] In the United States infections occasionally occur in rural areas and the bacteria is believed to circulate among rodents.[5] It has historically occurred in large outbreaks, with the best known being the Black Death in the 14th century, which resulted in greater than 50 million dead.[2]

Yersinia pestis fluorescent.jpeg
Yersinia pestis seen at 200× magnification with a fluorescent label.
SpecialtyInfectious disease
SymptomsFever, weakness, headache[1]
Usual onset1-7 days after exposure[2]
TypesBubonic plague, septicemic plague, pneumonic plague[1]
CausesYersinia pestis[2]
Diagnostic methodFinding the bacterium in a lymph node, blood, sputum[2]
PreventionPlague vaccine[2]
TreatmentAntibiotics and supportive care[2]
MedicationGentamicin and a fluoroquinolone[3]
Prognosis~10% risk of death (with treatment)[4]
Frequency~600 cases a year[2]

Signs and symptoms

Bubonic plague

Plague -buboes
Swollen inguinal lymph glands on a person infected with the bubonic plague. The swollen lymph glands are termed buboes from the Greek word for groin, swollen gland: bubo.

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, which drains interstitial fluid. Plague bacteria secrete several toxins, one of which is known to cause beta-adrenergic blockade.[6]

Y. pestis spreads through the lymphatic vessels of the infected human until it reaches a lymph node, where it causes acute lymphadenitis.[7] The swollen lymph nodes form the characteristic buboes associated with the disease,[8] and autopsies of these buboes have revealed them to be mostly hemorrhagic or necrotic.[9]

If the lymph node is overwhelmed, the infection can pass into the bloodstream, causing secondary septicemic plague and if the lungs are seeded, it can cause secondary pneumonic plague.[10]

Septicemic plague

Septicemic plague resulting in necrosis

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 (DIC), causing tiny clots throughout the body and possibly ischemic 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.[11][12][13] People who die from this form of plague often die on the same day symptoms first appear.

Pneumonic plague

The pneumonic form of plague arises from infection of the lungs. It causes coughing and sneezing and thereby produces airborne droplets that contain bacterial cells and are likely to infect anyone inhaling them. The incubation period for pneumonic plague is short, usually two to four days, but sometimes just a few hours. The initial signs are indistinguishable from several other respiratory illnesses; they include headache, weakness and spitting or vomiting of blood. The course of the disease is rapid; unless diagnosed and treated soon enough, typically within a few hours, death may follow in one to six days; in untreated cases mortality is nearly 100%.[14][15]


Xenopsylla chepsis (oriental rat flea)
The Oriental rat flea (Xenopsylla cheopsis) engorged with blood after a blood meal. This species of flea is the primary vector for the transmission of Yersinia pestis, the organism responsible for bubonic plague in most plague epidemics in Asia, Africa and South America. Both male and female fleas feed on blood and can transmit the infection.
Ulceration of flea bite cause by yersinia pestis
A child bitten by a flea infected with the bacterium Yersinia pestis. Y. pestis, a member of the family Enterobacteriaceae, has caused the bite to become ulcerated.

Transmission of Y. pestis to an uninfected individual is possible by any of the following means.[16]

  • 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 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.[16] Contrary to popular belief, rats did not directly start the spread of the bubonic plague. It is mainly a disease in the fleas (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 person 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.[17]


Since human plague is rare in most parts of the world, routine vaccination is not needed other than for those at particularly high risk of exposure, nor for people living in areas with enzootic plague, meaning it occurs at regular, predictable rates in populations and specific areas, such as the western United States. It is not even indicated for most travellers to countries with known recent reported 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).[18]

A systematic review by the Cochrane Collaboration found no studies of sufficient quality to make any statement on the efficacy of the vaccine.[19]


If diagnosed in time, the various forms of plague are usually highly responsive to antibiotic therapy. The antibiotics often used are streptomycin, chloramphenicol and tetracycline. Amongst the newer generation of antibiotics, gentamicin and doxycycline have proven effective in monotherapeutic treatment of plague.[20]

The plague bacterium could develop drug-resistance and again become a major health threat. One case of a drug-resistant form of the bacterium was found in Madagascar in 1995.[21] Further outbreaks in Madagascar were reported in November 2014[22] and October 2017[23].


World distribution of plague 1998
Distribution of plague infected animals 1998

Globally about 600 cases are reported a year.[2] In 2017 the countries with the most cases include the Democratic Republic of the Congo, Madagascar and Peru.[2] It has historically occurred in large outbreaks, with the best known being the Black Death in the 14th century which resulted in greater than 50 million dead.[2]

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/Huns, Mongols, Turks and other groups, to contaminate enemy water supplies. Han Dynasty General Huo Qubing 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 into cities under siege.

In 1347, the Genoese possession of Caffa, a great trade emporium on the Crimean peninsula, came under siege by an army of Mongol warriors of the Golden Horde 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. This event might have led to the transfer of the plague (Black Death) via their ships into the south of Europe, possibly explaining its rapid spread.[24]

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 Chinese, Korean and Manchurian civilians and prisoners of war with the plague bacterium. These subjects, termed "maruta" or "logs", were then studied by dissection, others by vivisection while still conscious. Members of the unit such as Shiro Ishii were exonerated from the Tokyo tribunal by Douglas MacArthur but 12 of them were prosecuted in the Khabarovsk War Crime Trials in 1949 during which some admitted having spread bubonic plague within a 36-km radius around the city of Changde.[25]

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 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.

The plague can be easily treated with antibiotics, which some countries, such as the United States, have large supplies on hand if such an attack should occur, thus making the threat less severe.[26]

See also


  1. ^ a b c d e f "Symptoms Plague". CDC. September 2015. Retrieved 8 November 2017.
  2. ^ a b c d e f g h i j k l m n o p q r "Plague". World Health Organization. October 2017. Retrieved 8 November 2017.
  3. ^ a b "Resources for Clinicians Plague". CDC. October 2015. Retrieved 8 November 2017.
  4. ^ a b "FAQ Plague". CDC. September 2015. Retrieved 8 November 2017.
  5. ^ "Transmission Plague". CDC. September 2015. Retrieved 8 November 2017.
  6. ^ Brown, SD; Montie, TC (1977). "Beta-adrenergic blocking activity of Yersinia pestis murine toxin". Infection and Immunity. 18 (1): 85–93. PMC 421197. PMID 198377.
  7. ^ Sebbane, F; Jarret, C.O.; Gardner, D; Long, D; Hinnebusch, B.J. (2006). "Role of Yersinia pestis plasminogen activator in the incidence of distinct septicemic and bubonic forms of flea-borne plague". Proc Natl Acad Sci U S A. 103 (14): 5526–5530. doi:10.1073/pnas.0509544103. PMC 1414629. PMID 16567636.
  8. ^ "Symptoms | Plague". Centers for Disease Control and Prevention. 14 September 2015. Retrieved 18 April 2017.
  9. ^ Sebbane, F; Gardner, D; Long, D; Gowen, B.B.; Hinnebusch, B.J. (2005). "Kinetics of Disease Progression and Host Response in a Rat Model of Bubonic Plague". Am J Pathol. 166 (5): 1427–1439. doi:10.1016/S0002-9440(10)62360-7. PMC 1606397. PMID 15855643.
  10. ^ "Plague". Centers for Disease Control and Prevention. Retrieved 2014-08-05.
  11. ^ Wagle PM (1948). "Recent advances in the treatment of bubonic plague". Indian J Med Sci. 2: 489–94.
  12. ^ Meyer KF (1950). "Modern therapy of plague". J Am Med Assoc. 144 (12): 982–85. doi:10.1001/jama.1950.02920120006003. PMID 14774219.
  13. ^ Datt Gupta AK (1948). "A short note on plague cases treated at Campbell Hospital". Ind Med Gaz. 83: 150–51.
  14. ^ Ryan, K. J.; Ray, C. G., eds. (2004). Sherris Medical Microbiology: An Introduction to Infectious Diseases (4th ed.). New York: McGraw-Hill. ISBN 978-0-8385-8529-0.
  15. ^ Hoffman SL (1980). "Plague in the United States: the "Black Death" is still alive". Annals of Emergency Medicine. 9 (6): 319–22. doi:10.1016/S0196-0644(80)80068-0. PMID 7386958.
  16. ^ a b Plague Manual: Epidemiology, Distribution, Surveillance and Control, pp. 9, 11. WHO/CDS/CSR/EDC/99.2
  17. ^ Yersin, Alexandre (1894). "La peste bubonique à Hong-Kong". Annales de l'Institut Pasteur. 8: 662–67.
  18. ^ "Plague Vaccine". CDC. June 11, 1982. Retrieved Apr 30, 2015.
  19. ^ Jefferson T, Demicheli V, Pratt M; Demicheli; Pratt (2000). Jefferson, Tom (ed.). "Vaccines for preventing plague". Cochrane Database Syst Rev (2): CD000976. doi:10.1002/14651858.CD000976. PMID 10796565.CS1 maint: Multiple names: authors list (link)
  20. ^ Mwengee W; Butler, Thomas; Mgema, Samuel; Mhina, George; Almasi, Yusuf; Bradley, Charles; Formanik, James B.; Rochester, C. George (2006). "Treatment of Plague with Genamicin or Doxycycline in a Randomized Clinical Trial in Tanzania". Clin Infect Dis. 42 (5): 614–21. doi:10.1086/500137. PMID 16447105.
  21. ^ Drug-resistant plague a 'major threat', say scientists, SciDev.Net.
  22. ^ "Plague – Madagascar". World Health Organisation. 21 November 2014. Retrieved 26 November 2014.
  23. ^ "WHO scales up response to plague in Madagascar". World Health Organization (WHO). 1 October 2017. Retrieved 5 October 2017.
  24. ^ Wheelis M. (2002). "Biological warfare at the 1346 siege of Caffa". Emerg Infect Dis. 8 (9): 971–75. doi:10.3201/eid0809.010536. PMC 2732530. PMID 12194776.
  25. ^ Daniel Barenblatt, A plague upon Humanity, HarperCollns, 2004, pp. 220–21
  26. ^ Tamparo, Carol; Lewis, Marcia (2011). Diseases of the Human Body. Philadelphia, PA: F.A. Davis Company. p. 70. ISBN 9780803625051.

External links

External resources
Ali az-Zahir

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Bonne of Luxembourg

Bonne of Luxemburg or Jutta of Luxemburg (20 May 1315 – 11 September 1349), was born Jutta (Judith), the second daughter of John the Blind, king of Bohemia, and his first wife, Elisabeth of Bohemia. She was the first wife of King John II of France; however, as she died a year prior to his accession, she was never a French queen. Jutta was referred to in French historiography as Bonne de Luxembourg. She was a member of the House of Luxembourg. Among her children were Charles V of France, Philip II, Duke of Burgundy, and Joan, Queen of Navarre.

Eric XII of Sweden

Eric "XII" (Swedish: Erik Magnusson; 1339 – 21 June 1359) was a rival king of Sweden, competing against his father, Magnus IV, from 1356 to his death in 1359. He was married to Beatrix of Bavaria, daughter of Emperor Louis IV.

In 1343 Eric and his brother, Haakon, were elected heirs of Sweden and Norway, respectively. That Haakon got the Norwegian throne in 1355 (causing the union between Norway and Sweden to split) while Eric didn't get any position in the Swedish council might have affected his choice to lead a rebellion against his father in 1355. In 1357 the rebellion had forced Magnus to share Sweden with his son Eric who got to rule most of Southern Sweden and Finland. Sweden was reunited again in 1359 when father and son became reconciled, and co-ruled Sweden until Eric's death a few months later. While dying Eric accused his mother, Blanche of Namur, of poisoning him. Quite soon after his death his wife, Beatrix, died too. It is generally believed that they died of the Black Death.

Hamnet Shakespeare

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John de Ufford

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Marco Antonio Bassetti

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Martin Opitz

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Michael Northburgh

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Northburgh's uncle's influence enabled him to be appointed Archdeacon of Chester in 1341 (until forced to resign in 1342) and Archdeacon of Suffolk in 1347 (until 1353) before he had been ordained into higher orders. Whilst archdeacon he became Rector of Pulham St. Mary (1341) and acquired a large number of canonries. He occupied the office of Lord Privy Seal between 1350 and 1354.Northburgh was elected Bishop of London on 22 April 1354 and consecrated on 12 July 1355. His most lasting achievement as bishop was in helping to found the Charterhouse. He bought land from Sir Walter de Manny and by his will left £2000 'for the foundation of a House according to the ritual of the Carthusian order in a place commonly called "Newchirchehawe", where there is a church of the Annunciation of the Blessed Virgin Mary.

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Northburgh died of the plague on 9 September 1361. In his will he left valuable books and artifacts to the illegitimate Michael Northborough, a future Archdeacon of Colchester.

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Born in one of the most important Venetian families, Morosini was extremely wealthy. Opinions about him are varied, though, and he is seen either as a devoted servant of the Republic, or as a speculator who enriched himself on real estate during the hard times of the War of Chioggia, fought between Venice and Genoa between 1378 and 1381.

Elected after the death of Doge Andrea Contarini, he died very soon of the plague and was buried in the church of San Zanipolo, a traditional burial place of the doges. He was married to Cristina Condulmiero.His statue (number 31) is erected in the outer ring in the southeast quarter of the Prato della Valle in Padova.

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Peter Binsfeld

Peter Binsfeld (alternate spelling Peter of Binsfeld, lat. Petrus Binsfeldius) (c. 1540 – 1598 or 1603) was a German bishop and theologian.

Peter, a son of a farmer and craftsman, was born in the village of Binsfeld in the rural Eifel region, located in the modern state of Rhineland-Palatinate; he died in Trier as a victim of the bubonic plague. Binsfeld grew up in the predominantly Catholic environment of the Eifel region.

Plague vaccine

Plague vaccine is a vaccine used against Yersinia pestis. Killed bacteria have been used since 1890 but are less effective against pneumonic plague so that recently live vaccines of an attenuated type and recombination protein vaccines have been developed to prevent the disease.

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