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A. Organism navigator

  1. Yersinia pestis is a Gram negative baccillus
    1. Family Enterobacteriaceae
    2. Facultative intracellular pathogen
    3. Related to Yersinia pseudotuberculosis
  2. Natural Reservoirs
    1. Carried by fleas; main route of transmission to humans
    2. Harbored in rats and other rodents
  3. In USA, endemic mainly in Arizona, Colorado
  4. Major concern is use as a biological weapon
  5. Incubation period 2-8 days from bite (usually by a flea)
  6. Epidemiology
    1. In 2000-2001, 95% of the ~36,000 cases of plague in Africa, most in Madagascar
    2. In 1987-2001, 125 cases in USA

B. Clinical Syndromes navigator

  1. Types of Syndromes
    1. Bubonic Plague
    2. Pneumonic Plague
    3. Septicemic Plague
  2. Bubonic Plague
    1. Most common form reported, >80% of cases
    2. Sudden onset of malaise, dizziness, high fever, prostration at time of lymphadenopathy
    3. Painful, tender, often erythematous lymph nodes ("buboes"), usually in groin, axilla
    4. Lymphadenopathy usually develops in groin, axilla or cervical regions
    5. May progress to pneumonic plague or meningitis without treatment
    6. Untreated bubonic plaque has mortality rate ~70%
  3. Pneumonic Plague
    1. Pneumonia results from inhalation of Y. pestis
    2. Pneumonia may progress to ARDS and is most common cause of death
    3. Inoculation period for pneumonic plague is 2-4 days
    4. Secondary pneumonic plague develops in ~10% of bubonic or septicemic plague cases
  4. Septicemic Plague
    1. Full blown sepsis syndrome occurs in 10-25% of cases
    2. Hypotension or frank shock present
    3. Intravascular coagulopathy common

C. Pathogenesis [1]navigator

  1. Facultative intracellular pathogen, mainly in macrophages
  2. Travels to regional lymph nodes from site of inoculation by traveling inside of macrophages
  3. Switches to extracellular multiplication, usually in lymph nodes
  4. Can survive inside macrophages but not neutrophils
  5. Neutrophils restrict growth of Yersinia pestis
  6. After dissemination, necrotic foci containing extraceullar Y pestis form
  7. Fewer than 10 infectious organisms subcutaneously required to cause death in 50%

D. Diagnosisnavigator

  1. High suspicion is critical
  2. Organism stain: gram negative coccobaccilus
  3. Immunoassay: F1 ELISA and rapid detection dipstick assays are available
    1. F1 dipstick assay on sputum is positive within ~48 hours of symptoms [4]
    2. Rapid diagnostic test for F1 antigen can detect plague within 15 minutes [5]
  4. Polymerase chain reaction (PCR) is available in selected laboratories

E. Therapy [1,2,3]navigator

  1. Aminoglycosides
    1. Streptomycin originally recommended, but gentamicin appears as effective
    2. Streptomycin 15mg/kg q12 hours IM (begin within 24 hours)
    3. Gentamicin 1.5mg/kg q8 hour IM also effective (preferred in pregnant women)
  2. Oral Agents
    1. High dosees may be as effective as aminoglycosides
    2. Tetracycline effective 500-1000mg qid PO x 10 days
    3. Doxycycline IV or po 200mg initial, then 100mg q12 hours
    4. Ciprofloxacin 400mg IV bid or 500mg po bid
    5. Chloramphenicol for meningitis: 25mg/kg IV initially then 15mg/kg q6 hours
  3. Multidrug Resistant
    1. Multidrug resistant strains reported; sensitive to trimethoprim [6]
    2. Trimethoprim/sulfamethoxazole (TMP/SMX) is effective but requires longer to work
  4. Therapy must be started early on in disease to be effective
  5. Post-exposure and mass-exposure prophylaxis guidelines have been established [2]

F. Prevention [1,2,3]navigator

  1. Plague vaccine is available and effective against bubonic plague
  2. However, vaccine would probably not prevent primary pneumonic plague
  3. New vaccine for protection against pneumonic plague is under development
  4. Chemoprophylaxis with sulphadoxine (Fanasil®) 2gm for adults is highly effective [4]

References navigator

  1. Prentice MB and Rahalson L. 2007. Lancet. 369(9568):1196 abstract
  2. Inglesby TV, Dennis DT, Henderson DA, et al. 2000. JAMA. 283(17):2281 abstract
  3. Drugs and Vaccines Against Biological Weapons. 1999. Med Let. 41(1046):15 abstract
  4. Ratsitorahina M, Chanteau S, Rahalison L, et al. 2000. Lancet. 355(9198):111 abstract
  5. Chanteau S, Sahalison L, Ralafiarisoa L, et al. 2003. Lancet. 361(9353):211 abstract
  6. Galimand M, Guiyoule A, Gerbaud G, et al. 1997. NEJM. 337(10):677 abstract