II. Epidemiology

  1. Madagascar (fall 2017)
    1. Cases: 1800 as of November 2017
    2. Deaths: 127 as of November 2017
    3. http://www.who.int/csr/disease/plague/en
  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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