• See Also
  1. Enterobacteriaceae
  2. Gram Negative Bacteria
  3. Bioterrorism
  4. Lymphadenitis
  • 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 (25 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
    2. Resulted in 12-15 Million deaths worldwide
    3. Onset in China 1855, and later spread to India
    4. Large outbreak in Hong Kong, China (1894)
    5. Outbreak in San Francisco, California (1900-1904)
  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. Resulted in 11 cases and 3 deaths
      2. Lymph Node involvement was absent in up to 25% of cases
      3. Desert Southwest (Arizona, New Mexico) and Yosemite National Park
      4. Kwit (2015) MMWR Morb Mortal Wkly 64(33): 618-9 [PubMed]
  • Pathophysiology
  1. Yersinia Pestis
    1. Gram Negative Rod (some characterize as coccobacillus)
    2. Bipolar staining (Bacterial cell center stains less than the ends)
    3. Facultative anaerobic and Intracellular Bacteria
  2. Incubation
    1. Pneumonic Plague: 2-3 up to 6 days
    2. Bubonic Plague: 2-10 days
  3. 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
  4. Transmission
    1. Reservoir: Rodents (rats, mice, ground squirrels, prairie dogs)
    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
    4. Episodic cases occur between epidemics
      1. Outdoor activities (camping, hiking, hunting) with infected Flea Bites or contact with rodent carcus
  5. Bubonic Plague Infection (primary disease form)
    1. Yersinia Pestis invades skin after Flea Bite
    2. Macrophages phagocytose Yersinia
      1. Yersinia survives within Macrophages (see mechanisms below)
      2. Yersinia multiplies within Macrophages and moves to regional Lymph Nodes within the first week
    3. Buboes
      1. Develop within regional Lymph Nodes (esp. inguinal region)
      2. Bacteremia follows with systemic spread
  6. Resistance to Macrophage Phagocytosis
    1. Fraction 1 (F1)
      1. Capsular Antigen with anti-Phagocytosis activity
    2. V Antigen
      1. Protein unique to Yersinia species
    3. W Antigen
      1. Lipoprotein unique to Yersinia species
  • 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)
  • 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. Lymph Node swelling was absent during the 1980-1984 New Mexico outbreak
  3. Septicemic Plague
    1. Abdominal Pain
    2. Subcutaneous Hemorrhage
      1. Gives skin a black discoloration, resulting in the name "black death"
    3. Disseminated Intravascular Coagulation
    4. Digital necrosis
  • 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
  • Imaging
  • Pneumonic Plague
  1. Chest XRay
    1. Rapidly progresses from segmental to lobar consolidative Pneumonia, then multilobar and bilateral
  • Differential Diagnosis
  1. Bubonic Plague
    1. See Regional Lymphadenopathy
    2. Streptococcal or staphylococcal Lymphadenitis
    3. Tularemia
    4. Cat Scratch Disease
    5. Mycobacterium (including Tuberculosis)
    6. Acute filarial Lymphadenitis
    7. Chancroid (or other STI with Regional Lymphadenitis)
    8. Strangulated Inguinal Hernia
  2. Septicemic Plague
    1. Gram NegativeSepsis
    2. Meningococcemia
    3. Bacterial Endocarditis
  3. Pneumonic Plague
    1. Acute Respiratory Distress Syndrome
    2. Bacterial Pneumonia
      1. Pneumococcal Pneumonia
      2. Mycoplasma pneumonia
      3. Staphylococcal Pneumonia
      4. Legionnaire's Disease
      5. TularemiaPneumonia
      6. Q Fever
    3. Severe Viral Pneumonia
      1. Covid19
      2. Hantavirus Pulmonary Syndrome
      3. Severe Acute Respiratory Syndrome (SARS)
  4. References
    1. Dennis (2006) Tropical Infectious Diseases
      1. https://pmc.ncbi.nlm.nih.gov/articles/PMC7152251/
  • 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
  • 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 orally twice daily
    3. Ciprofloxacin 500 mg orally twice daily
    4. Tetracycline 500 mg orally four times daily
  • Prognosis
  1. Mortality
    1. Bubonic Plague: 30% and 60% (decreased to 10% with prompt treatment)
    2. Pneumonic Plague: 100% if untreated or treatment delayed >24 to 48 hours (decreased to 50% with treatment)
  • 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]