II. History

  1. First Plague Pandemic (Europe and Mediterranean, series of Plagues 541–767)
    1. https://en.wikipedia.org/wiki/First_plague_pandemic
  2. Black Death (Europe, 1346 to 1353, start of the second Plague pandemic)
    1. https://en.wikipedia.org/wiki/Black_Death
    2. Killed 20 to 50 million europeans (up to 50% of europe population)
    3. Spread from Asia and Crimea to Europe via rat infested ships
  3. Third Plague pandemic (China and India, 1855–1960)
    1. https://en.wikipedia.org/wiki/Third_plague_pandemic
  4. Recent Plague Outbreaks
    1. Madagascar (fall 2017)
      1. Cases: 1800 as of November 2017
      2. Deaths: 127 as of November 2017
    2. U.S. (2015)
      1. Cases: 11 with 3 deaths
      2. Desert Southwest (Arizona, New Mexico) and Yosemite National Park
      3. Kwit (2015) MMWR Morb Mortal Wkly 64(33): 618-9 [PubMed]

III. Pathophysiology

  1. Bacteria: Yersinia pestis
  2. Gram Negative Rod (some characterize as coccobacillus)
    1. Bipolar staining
    2. Facultative anaerobic bacterium
  3. Incubation
    1. Pneumonic Plague: 2-3 up to 6 days
    2. Bubonic Plague: 2-10 days
  4. Organism survival
    1. Viability
      1. Water, moist meal, grain for weeks
      2. Near freezing Temperatures from months to years
      3. Dry Sputum, flea feces, buried bodies
    2. Killed by
      1. Heated for 15 minutes at 72 C
      2. Several hours in direct sunlight
  5. Transmission
    1. Reservoir: Rodents (rats, mice, ground squirrels)
    2. Arthropod Bites (e.g. Flea Bites) transmit bubonic form
    3. Aerosolized organisms transmit pneumonic form (e.g. Bioterrorism, person-to-person transmission)
      1. Infective Dose: 100 to 500 organisms need be inhaled for infection (moderately infective)
      2. Highly contagious in later stages of Pneumonic Plague with productive, purulent cough
      3. Keep infected patients under strict droplet precautions until 48 hours after Antibiotics started

IV. Types: Plague

  1. Bubonic Plague (80-95% of cases)
    1. Non-fluctuant inguinal Lymphadenitis
    2. Follows bite of an infected flea
  2. Primary septicemic Plague (10-20% of cases)
    1. May complicate Bubonic Plague or Pneumonic Plague
    2. Hematologic spread to other tissues and may result in lung involvement as well (Pneumonic Plague)
    3. Gastrointestinal symptoms predominate early
    4. Multiorgan failure, DIC, Sepsis occur later
  3. Pneumonic Plague (rare)
    1. Hematogenous seeding or droplet inhalation (highly contagious)
    2. Occurs from person-to-person transmission (or aeroslized Biological Weapon)
    3. Mortality >60% with treatment (approaches 100% without treatment)

V. Findings: Symptoms and signs

  1. Pneumonic Plague
    1. High fever
    2. Chills
    3. Headache
    4. Productive cough with Hemoptysis
    5. Toxic appearance
    6. Rapidly fulminant Pneumonia within 2-3 days of exposure
    7. Disseminated Intravascular Coagulation (DIC) or Shock may ensue
  2. Bubonic Plague
    1. Malaise
    2. High fever
    3. Tender, swollen Lymph Nodes (buboes)
      1. Primarily inguinal (legs most commonly flea bitten)
      2. Nodes swell and may become hemorrhagic and necrotic
  3. Septicemic Plague
    1. Abdominal Pain
    2. Subcutaneous Hemorrhage
    3. Disseminated Intravascular Coagulation
    4. Digital necrosis

VI. Labs

  1. Fluid Gram Stain and culture (from Sputum, tracheal aspirates, blood or aspirated buboe)
    1. Yersinia pestis Antigen detection or PCR
    2. Gram Negative Bacilli with "safety pin" appearance
    3. Organism grows on standard culture medium

VII. Imaging: Pneumonic Plague

  1. Chest XRay
    1. Rapidly progresses from segmental to lobar consolidative Pneumonia, then multilobar and bilateral

VIII. Management

  1. Treat for 10-14 days
  2. Contact Isolation
    1. Strict Droplet Isolation for plague Pneumonia patients for first 48 hours after Antibiotics started
    2. Healthcare staff should wear surgical masks (N95 Masks if performing aerosolizing procedures)
    3. Keep patient in private room, but negative airflow room is NOT needed
  3. Preferred Regimens (choose one)
    1. Streptomycin
      1. Adults and Children: 15 mg/kg (up to 1 to 2 g) IV/IM every 12 hours
    2. Gentamicin
      1. Adult: 5 mg/kg IM or IV every 24 hours
      2. Child: 2.5 mg/kg IM or IV every 8 hours
  4. Other Regimens (choose one)
    1. Doxycycline (over age 8 years)
      1. Convert to oral dosing when clinically improved
      2. Adult: 200 mg IV, then 100 mg IV every 12 hours
      3. Child: 2.2 mg/kg IV (max: 100 mg) every 12 hours
        1. Dose as adult for children over 45 kg
    2. Ciprofloxacin
      1. Adult: 400 mg IV every 12 hours
        1. When improved convert to 750 mg orally twice daily
      2. Child: 15 mg/kg (max: 400 mg) IV every 12 hours
    3. Chloramphenicol
      1. Adult: 1 g IV every 6 hours
      2. Child: 25 mg/kg (max: 1 g) IV every 6 hours

IX. Prevention

  1. Eliminate infected vectors (fleas, rodents)
  2. Exposure to sunlight kills Y. pestis within hours
    1. However Y. pestis is viable in soil or grain for several weeks
  3. Licensed, killed Vaccine (no longer available)
    1. Doses at 0, 1-3 months, and 5-6 months
    2. Booster at 6 month intervals x3, then every 1-2 years
    3. Effective against bubonic, but not pulmonic Plague
  4. Post-exposure Prophylaxis (adult dosing below)
    1. Continue for 7 days or length of exposure
    2. Doxycycline 100 mg PO bid
    3. Ciprofloxacin 500 mg PO bid
    4. Tetracycline 500 mg PO qid

X. Prognosis

  1. Pneumonic Plague Mortality 100% if untreated (or treatment delayed >24 to 48 hours)

XI. References

  1. Charbonnet and Mace (2023) Crit Dec Emerg Med 37(4): 4-10
  2. Gilbert (2019) Sanford Guide, accessed 1/27/2020 on IOS version
  3. Seeyave (2015) Crit Dec Emerg Med 29(5): 13-21
  4. Inglesby (2000) JAMA 283:2281-90 [PubMed]
  5. Rathjen (2021) Am Fam Physician 104(4): 376-85 [PubMed]

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Related Studies

Ontology: Plague (C0032064)

Definition (CHV) an infectious disease
Definition (CHV) an infectious disease
Definition (CHV) an infectious disease
Definition (CHV) an infectious disease
Definition (MEDLINEPLUS)

Plague is an infection caused by the bacterium Yersinia pestis. The bacteria are found mainly in rats and in the fleas that feed on them. People and other animals can get plague from rat or flea bites. In the past, plague destroyed entire civilizations. Today plague is uncommon, due to better living conditions and antibiotics.

There are three forms of plague:

  • Bubonic plague causes the tonsils, adenoids, spleen, and thymus to become inflamed. Symptoms include fever, aches, chills, and tender lymph glands.
  • In septicemic plague, bacteria multiply in the blood. It causes fever, chills, shock, and bleeding under the skin or other organs.
  • Pneumonic plague is the most serious form. Bacteria enter the lungs and cause pneumonia. People with the infection can spread this form to others. This type could be a bioterror agent.

Lab tests can diagnose plague. Treatment is a strong antibiotic. There is no vaccine.

NIH: National Institute of Allergy and Infectious Diseases

Definition (NCI) A Gram-negative bacterial infection caused by Yersinia pestis. It is usually transmitted to humans from bites of infected rodent fleas. It is manifested as a bubonic, septicemic, or pneumonic plague. In bubonic plague, the lymph nodes adjacent to the site of the skin bite are infected and enlarged. In septicemic plague, the infection spreads directly through the bloodstream. In pneumonic plague, the infection spreads to the lungs either following bubonic plague, or by inhalation of infective droplets. If untreated, it may lead to death.
Definition (MSH) An acute infectious disease caused by YERSINIA PESTIS that affects humans, wild rodents, and their ectoparasites. This condition persists due to its firm entrenchment in sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form.
Definition (CSP) acute infectious disease caused by Yersinia pestis that affects humans, wild rodents, and their ectoparasites; bubonic plague is the most common form.
Concepts Disease or Syndrome (T047)
MSH D010930
ICD9 020.9, 020
ICD10 A20 , A20.9
SnomedCT 187298009, 186290009, 58750007
LNC LA10495-2
English Yersinia pestis disease, Plague unspecified, Plague, unspecified, Yersinia pestis plague (diagnosis), Yersinia pestis plague, plague, plague (diagnosis), Yersinia pestis infection, Unspecified plague, Plague NOS, Plague [Disease/Finding], pest, pestilential fever, plagues, Plague unspecified (disorder), Infection by Yersinia pestis, Pest, Pestilential fever, Plague (disorder), Pasteurella; infection, pestis, Yersinia pestis; infection, infection; Pasteurella, pestis, infection; Yersinia pestis, Plague, NOS, Plague
Dutch pest, niet-gespecificeerd, Yersinia pestis-infectie, niet-gespecificeerde pest, Pasteurella; infectie, pestis, Yersinia pestis; infectie, infectie; Pasteurella, pestis, infectie; Yersinia pestis, Pest, niet gespecificeerd, pest, Bubonenpest, Pest
French Infection à Yersinia pestis, Peste, non précisée, Peste non précisée, Peste
German Pest, unspezifisch, Yersinia pestis-Infektion, unspezifische Pest, Pest, nicht naeher bezeichnet, Pest
Italian Infezione da Yersinia pestis, Peste non specificata, Peste
Portuguese Peste NE, Infecção por Yersinia pestis, Peste
Spanish Infección por Yersinia pestis, Peste no especificada, peste no especificada (trastorno), peste no especificada, Plague unspecified, infección por Yersinia pestis, peste (trastorno), peste, Peste
Japanese 詳細不明のペスト, ペスト菌感染, ペスト、詳細不明, ペスト, ペストショウサイフメイ, ショウサイフメイノペスト, ペストキンカンセン, 腺ペスト, 黒死病, 黒死症, ペスト
Swedish Pest
Czech mor, Infekce Yersinia pestis, Blíže neurčený mor, Mor, Mor, blíže neurčený
Finnish Rutto
Russian CHUMA, ЧУМА
Korean 페스트, 상세불명의 페스트
Polish Dżuma, Zakażenie Yersinia pestis
Hungarian Pestis, nem meghatározott, Nem meghatározott pestis, Yersinia pestis fertőzés, pestis
Norwegian Pest

Ontology: Yersinia pestis (C0043408)

Definition (NCI) A species of facultatively anaerobic, Gram negative, rod shaped bacteria in the phylum Proteobacteria. This species is motile, positive for coagulase and fibrinolysin and negative for urease, indole, ornithine decarboxylase, oxidase, and pyrazinamidase. Some strains are able to ferment melibiose but none can metabolize sorbose, rhamnose, cellobiose, sucrose, or sorbitol. Y. pestis is found in rodents and fleas and is a pathogen that can cause pneumonic, septicemic and bubonic plague types in humans.
Definition (NCI_CDISC) Any bacterial organism that can be assigned to the species Yersinia pestis.
Definition (CSP) etiologic agent of plague in humans, rats, ground squirrels, and other rodents.
Definition (MSH) The etiologic agent of PLAGUE in man, rats, ground squirrels, and other rodents.
Concepts Bacterium (T007)
MSH D015010
SnomedCT 54365000
LNC LP30923-4, MTHU015543
English Pasteurella pestis, Yersinia pestis, Yersinia pseudotubercul pestis, Y. pestis, Yersinia pseudotuberculosis subsp. pestis (Lehmann and Neumann 1896) Bercovier et al. 1981, Yersinia pestis (Lehmann and Neumann 1896) van Loghem 1944 (Approved Lists 1980), nom. cons, yersinia pestis, pestis y, y. pestis, pasteurella pestis, pestis yersinia, Bacillus pestis, Bacterium pestis, Pestisella pestis, Yersinia pseudotuberculosis subsp. pestis, YERSINIA PESTIS, PASTEURELLA PESTIS, Yersinia pseudotuberculosis subsp pestis, Yersinia pestis (organism)
Swedish Yersinia pestis
Czech Yersinia pestis, Pasteurella pestis
Finnish Yersinia pestis
Russian CHUMNAIA PALOCHKA, CHUMY VOZBUDITEL', ЧУМНАЯ ПАЛОЧКА, ЧУМЫ ВОЗБУДИТЕЛЬ
Italian Pasteurella pestis, Yersinia pestis
Polish Yersinia pestis, Pałeczki dżumy
Japanese エルシア・ペスティス, ペスト菌, エルシニアペスチス, パスツレラペスチス
Norwegian Pasteurella pestis, Yersinia pestis
Spanish Yersinia pestis (organismo), Yersinia pseudotuberculosis subespecie pestis, Yersinia pestis, Pasteurella pestis
French Pasteurella pestis, Yersinia pestis
German Pasteurella pestis, Yersinia pestis
Dutch Pasteurella pestis, Yersinia pestis
Portuguese Pasteurella pestis, Yersinia pestis

Ontology: Bubonic Plague (C0282312)

Concepts Disease or Syndrome (T047)
MSH D010930
ICD9 020.0
ICD10 A20.0
SnomedCT 50797007, 58750007
English Plague, Bubonic, BUBONIC PLAGUE, black death, bubonic plague, bubonic plague (diagnosis), Bubonic Plague, black deaths, black plague, Black plague, Bubonic plague, Black death, Bubonic plague (disorder), bubonic; plague, plague; bubonic
Dutch zwarte pest, bubonen; pest, pest; bubonen, builenpest, Builenpest
French Peste noire, Peste bubonique
German schwarzer Tod, Bubonenpest, Beulenpest
Portuguese Peste negra, Peste Bubônica, Peste bubónica
Spanish Peste negra, Peste Bubónica, peste bubónica (trastorno), peste bubónica, peste fulminante, peste glandular, peste mayor, Peste bubónica
Japanese 腺ペスト, 黒死病, センペスト, コクシビョウ
Italian Peste bubbonica
Czech Bubonický mor, Černý mor, bubonický mor, dýmějový mor
Korean 림프절형 페스트
Hungarian bubopestis, Fekete pestis
Norwegian Bubonpest, Byllepest

Ontology: Pneumonic Plague (C0524688)

Concepts Disease or Syndrome (T047)
MSH D010930
ICD9 020.5
ICD10 A20.2
SnomedCT 186283004, 38976008
English Pneumonic plague, unspecified, PLAGUE PNEUMONIA, Plague, Pneumonic, Plagues, Pneumonic, Pneumonic Plagues, pneumonic plague (diagnosis), pneumonic plague, Pneumonic, unspecified plague, Pneumonic plague NOS, plague pneumonic, Pneumonic plague, unspecified (disorder), Pneumonic plague, Pneumonic plague (disorder), Yersinia pestis; pneumonia, lung; plague, plague; lung, plague; pneumonica, plague; pulmonary, pneumonia; Yersinia pestis, pulmonary; plague, Pneumonic plague, NOS, Pneumonic Plague, pneumonic; plague
Italian Peste polmonare, Peste polmonare non specificata, Peste pneumonica
Dutch pneumonische pest, niet-gespecificeerd, pneumonie, niet-gespecificeerde plaag, Yersinia pestis; pneumonie, long; pest, pest; long, pest; pneumonica, pest; pulmonaal, pneumonie; Yersinia pestis, pulmonaal; pest, Pneumonische vorm van pest, pneumonische pest, pneumonica; pest, Longpest
French Peste pneumonique, non précisée, Peste pneumonique, Peste pulmonaire
German Lungenpest, unspezifisch, Lunge, unspezifische Pest, Lungenpest
Portuguese Peste pneumónica NE, Peste Pneumônica, Peste pneumónica
Spanish Peste neumónica no especificada, Peste Neumónica, neumonía por peste, no especificada, neumonía por peste, no especificada (trastorno), neumonía pestosa, no especificada (trastorno), neumonía pestosa, no especificada, peste neumónica (trastorno), peste neumónica, Peste neumónica
Japanese 肺ペスト、詳細不明, 肺ペスト, ハイペストショウサイフメイ, ハイペスト
Czech Plicní mor, Plicní blíže neurčený mor, Plicní mor, blíže neurčený, plicní mor, pneumonický mor
Korean 폐렴형 페스트
Hungarian tüdőpestis, tüdőpestis, nem meghatározott, Pneumoniás, nem meghatározott pestis
Norwegian Pneumonisk pest