Vector

Tularemia

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Tularemia, Francisella tularensis, Rabbit Fever

  • See Also
  1. Tick-Borne Disease
  2. Vector Borne Disease
  3. Prevention of Tick-borne Infection
  4. Tick Removal
  5. Bioterrorism
  • Epidemiology
  1. Peak onset in summer and fall
  2. Endemic areas in United States (>50% of cases)
    1. Arkansas
    2. Missouri
    3. Oklahoma
  • Pathophysiology
  1. Francisella tularensis is causative organism
    1. Small, aerobic Gram-Negative Bacteria
    2. Non-motile coccobacillus
    3. Primarily found in the northern hemisphere
  2. Carriers of F. tularensis
    1. Mammals
      1. Rabbits (most common vector, direct contact)
      2. Wild rodents
      3. Bobcats
    2. Deer Fly (Chrysops discalis)
    3. Tick Vector
      1. Amblyomma americanum (Lone star tick)
      2. Dermacentor variabilis (Dog tick)
  3. Transmission
    1. No person to person transmission
    2. Tick Bite (accounts for 50% of U.S. cases)
    3. Risk of exposure as Biological Weapon (inhalation of aerosolized Biological Weapon)
      1. Highly infective
      2. Infective Dose: Only 10 to 50 organisms need be inhaled for infection
      3. Aerosolized F. tularensis decreases 90% within 30 to 60 minutes after exposure to Ambient air at room Temperature
    4. Contaminated water ingestion or undercooked meat ingestion
    5. Skin contact with infected animals (most common transmission)
    6. Small outbreaks of inhalational Tularemia have occurred from contaminated grass or brush clippings
  4. Disease pathogenesis
    1. Bacteria pentrates skin or mucosal surface
    2. Spreads to regional Lymph Nodes
    3. Disease replicates and forms Granulomas with central necrosis
    4. Untreated disease disseminates rapidly
  5. Incubation: 1 to 14 days
  • Symptoms
  • Constitutional (follows 3-5 day incubation)
  1. Fever and chills (all types)
  2. Headache
  3. Malaise or Fatigue
  4. Anorexia
  5. Vomiting
  6. Pharyngitis
  7. Abdominal Pain
  8. Diarrhea
  9. Chest discomfort
  10. Myalgias
  • Type Specific Signs (divided over 6 classic types)
  1. Ulceroglandular Type (most common)
    1. Lymphadenopathy as in Glandular type
    2. Painful Skin Ulcer at site of vector bite and in region of Lymphadenopathy
  2. Glandular Type
    1. Unlike ulceroglandular infection, there is no skin bite site, only Lymphadenopathy
    2. Localized, tender Lymphadenopathy
      1. Children: Cervical and occipital Lymph Nodes
      2. Adults: Inguinal Lymph Nodes
  3. Oculoglandular Type
    1. Occurs when eye is splashed with contaminated water
    2. Conjunctiva involvement
      1. Unilateral in 90% of cases
      2. Early symptoms
        1. Photophobia
        2. Increased Lacrimation
      3. Later signs
        1. Lid edema
        2. Painful Conjunctivitis
        3. Scleral injection
        4. Chemosis
        5. Small yellow Conjunctival ulcers or Papules
    3. Lymphadenopathy as in Glandular type above
      1. Preauricular, Submandibular, and Cervical nodes
  4. Pharyngeal Type
    1. Associated with contaminated foodborne infection or waterborne infection
    2. Exudative Pharyngitis with severe Sore Throat
    3. Lymphadenopathy as in Glandular Type
      1. Cervical, pre-parotid and retropharyngeal nodes
  5. Typhoidal Type
    1. No significant Lymphadenopathy
    2. Profuse watery Diarrhea
    3. Bacteremia with Hypotension
  6. Pneumonic Type (most severe type)
    1. Follows a 2 to 14 day Incubation Period
    2. Non-productive cough, Headache, rigors, Pharyngitis, myalgias, Low Back Pain
    3. Substernal and Pleuritic Chest Pain
    4. Infiltrates may be seen on Chest XRay
    5. Mortality approaches 60% with untreated severe variants
    6. Distinguishing Features
      1. Pulse-Temperature Dissociation
      2. Pleural Effusions
      3. Prominent Hilar Adenopathy
  • Labs
  1. Inflammatory markers normal
    1. Erythrocyte Sedimentation Rate (ESR) near normal
    2. Complete Blood Count
      1. White Blood Cell Count near normal
  • Diagnosis
  1. Rapid identification requires special testing facilities
    1. Routine testing (cultures) will take weeks to grow the organism
  2. Sputum, tracheal aspirates, pharyngeal washings, gastric aspirates (rarely isolated from blood)
    1. PCR
    2. Direct fluorescent Antibody
    3. Immunohistochemical testing
    4. Sputum Culture or Blood Culture on Cysteine enriched media
      1. Lab workers are at risk of transmission (warn of suspicion for Tularemia)
  3. Tularemia Serology
    1. Confirms diagnosis at two weeks
  • Management
  1. Isolation not required
    1. No known person-to-person transmission
  2. Risk of Jarisch-Herxheimer Reaction with treatment
  3. Antibiotic regimens are similar to those used in Plague
  4. Mild Disease (high relapse rate with these agents)
    1. Doxycycline (avoid under age 8 years)
      1. Dose: 100 mg oral or IV twice daily for 14 to 21 days
    2. Ciprofloxacin (cartilage risk under age 18 years)
      1. Dose: 400 mg IV q12 hours for 14 to 21 days
      2. When improved convert to 750 mg oral twice daily
    3. Alternatives in pregnancy: Streptomycin, Chloramphenicol
  5. Moderate to Severe Disease - Non-Meningitis cases (choose 1 agent)
    1. Streptomycin
      1. Dose: 15 mg/kg up to 1 g IM or IV every 12 hours for 10 to 14 days
      2. Some protocols, allow dose to drop to 500 mg IV/IM daily for 5 days once affebrile
      3. Do not use for Meningitis
    2. Gentamicin or Tobramycin
      1. Adult: 5 mg/kg IM or IV every 24 hours for 10 to 14 days
      2. Child: 2.5 mg/kg IM or IV every 8 hours for 10 to 14 days
  6. Meningitis
    1. Gentamicin or Tobramycin (at dose above) AND
    2. Chloramphenicol 50-100 mg/kg/day divided q6 hours IV
  • Prevention
  1. Live Attenuated Vaccine 0.1 ml dose via scarification
    1. Previously available Vaccine (to protect lab workers) is no longer available
  2. Post-exposure Prophylaxis (adult dosing below) after aerosol exposure
    1. Continue for 14 days or length of exposure
    2. Doxycycline (over age 8 years)
      1. Adults: 100 mg orally twice daily
      2. Child: 2.2 mg/kg (max: 100 mg) orally every 12 hours (only if over age 8 years old)
    3. Ciprofloxacin
      1. Adult: 500 mg orally twice daily
      2. Child: 15 mg/kg (max: 500 mg) orally twice daily (avoid under age 18 if possible, cartilage risk)
    4. Tetracycline
      1. Adults: 500 mg orally four times daily
  • Prevention
  1. See Prevention of Vector-borne Infection
  2. Live Vaccine if high risk of exposure
  3. Handlers of rabbits and rodents (live or dead) should wear gloves
  • Prognosis
  1. Mortality <2%
  2. Mortality for untreated pneumonic type with virulent strain: 60%
  • Resources
  1. CDC: Tularemia
    1. http://www.cdc.gov/tularemia/
  • References
  1. (2018) Sanford Guide, accessed IOS app 1/30/2020
  2. Seeyave (2015) Crit Dec Emerg Med 29(5): 13-21
  3. Charbonnet and Mace (2023) Crit Dec Emerg Med 37(4): 4-10
  4. Dennis (2001) JAMA 285(21):2763-73 [PubMed]
  5. Huntington (2016) Am Fam Physician 94(7): 551-7 [PubMed]
  6. Maurin (2011) Clin Infect Dis 53(10): e133-41 +PMID:22002987 [PubMed]
  7. Nigrovic (2008) Infect Dis Clin North Am 22(3): 489-504 +PMID:18755386 [PubMed]
  8. Pace (2020) Am Fam Physician 101(9): 530-40 [PubMed]
  9. Rathjen (2021) Am Fam Physician 104(4): 376-85 [PubMed]