Tularemia

Aka: Tularemia, Francisella Tularensis, Rabbit Fever

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II. Epidemiology

  1. Peak onset in summer and fall
  2. Endemic areas in United States (>50% of cases)
    1. Arkansas
    2. Missouri
    3. Oklahoma

III. Pathophysiology

  1. Francisella Tularensis is causative organism
    1. Small, non-motile, aerobic gram-negative rod or coccobacillus
    2. Highly virulent and infections occur from even a dozen Bacteria
    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 (esp rabbits, most common transmission)
      1. Skinning and evisceration of infected mammals (e.g. rabbits) can also aerosolize Bacteria (causing Pneumonia)
    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

IV. 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

V. Type Specific Signs (divided over 6 classic types)

  1. Ulceroglandular Type (most common)
    1. Regional Lymphadenopathy as in Glandular type
      1. Swollen, red, painful regional Lymph Nodes (drainage may occur)
      2. Systemic spread may occur
    2. Skin entry site becomes well defined with a black base
      1. Painful Skin Ulcer at site of vector bite
  2. Glandular Type
    1. Unlike ulceroglandular infection, there is no skin bite site, only Lymphadenopathy
    2. Localized, tender Lymphadenopathy (similar to buboes in Bubonic Plague)
      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. Occurs with systemic spread of ulceroglandular type or with aerosolized Bacteria inhalation (e.g. skinning rabbits)
    2. Follows a 2 to 14 day Incubation Period
    3. Non-productive cough, Headache, rigors, Pharyngitis, myalgias, Low Back Pain
    4. Substernal and Pleuritic Chest Pain
    5. Infiltrates may be seen on Chest XRay
    6. Mortality approaches 60% with untreated severe variants
    7. Distinguishing Features
      1. Pulse-Temperature Dissociation
      2. Pleural Effusions
      3. Prominent Hilar Adenopathy

VI. Labs

  1. Inflammatory markers normal
    1. C-Reactive Protein and Erythrocyte Sedimentation Rate (ESR) near normal
    2. Complete Blood Count
      1. White Blood Cell Count near normal

VII. 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

VIII. Management

  1. Isolation not required
    1. No known person-to-person transmission
    2. However, do NOT aspirate Lymph Nodes (risk of contagious spread)
  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

IX. 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

X. 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

XI. Prognosis

  1. Mortality <2%
  2. Mortality for untreated pneumonic type with virulent strain: 60%

XII. Resources

  1. CDC: Tularemia
    1. http://www.cdc.gov/tularemia/

XIII. 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]

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Related Studies

Ontology: FRANCISELLA TULARENSIS (C0016677)

Definition (NCI_CDISC) Any bacterial organism that can be assigned to the species Francisella tularensis.
Definition (NCI) A species of aerobic, Gram negative, coccobacilli shaped bacterium in the phylum Proteobacteria. It has two main serotypes, Jellison Type A and Jellison Type B. This species is hemolytic, oxidase negative, catalase positive and nonfermentative. F. tularensis is pathogenic, being a causative agent of Tularemia which is mainly contracted when handling infected rabbits. This bacterium has been classified as a Category A critical biological agent due to its ease of dissemination by aerosol, causing high mortality with the potential for a major public health impact.
Definition (CSP) species in the family Francisellaceae; the etiologic agent of tularemia.
Definition (MSH) The etiologic agent of TULAREMIA in man and other warm-blooded animals.
Concepts Bacterium (T007)
MSH D005604
SnomedCT 51526001
LNC LP14119-9, MTHU015542
English Francisella tularensis, Pasteurella tularensis, Francisella tularensis (McCoy and Chapin 1912) Dorofe'ev 1947, francisella tularensis, Bacterium tularense, Brucella tularensis, Francisella tularense, FRANCISELLA TULARENSIS, PASTEURELLA TULARENSIS, Francisella tularensis (organism)
French Pasteurella tularensis, Bacillus tularensis, Brucella tularensis, Francisella tularensis
Swedish Francisella tularensis
Czech Francisella tularensis
Finnish Francisella tularensis
Russian TULIAREMII VOZBUDITEL', TULIAREMIIA, VOZBUDITEL', PASTEURELLA TULARENSIS, ТУЛЯРЕМИИ ВОЗБУДИТЕЛЬ, ТУЛЯРЕМИЯ, ВОЗБУДИТЕЛЬ
Japanese フランシセラ･ツラレンシス, パスツレラツラレンシス, 野兎病菌, フランシセラツラレンシス
Italian Pasteurella tularensis, Francisella tularensis
Polish Pasteurella tularensis, Pałeczki tularemii
Norwegian Francisella tularensis, Pasteurella tularensis
Spanish Francisella tularensis (organismo), Francisella tularensis, Pasteurella tularensis
German Francisella tularensis, Pasteurella tularensis
Dutch Francisella tularensis, Pasteurella tularensis, Tularemie-bacterie
Portuguese Francisella tularensis, Pasteurella tularensis
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Tularemia (C0041351)

Definition (MSHCZE) Bakteriální infekční onemocnění převážně drobných hlodavců a zajíců („zaječí nemoc, zaječí mor"), od nichž je možná nákaza člověka (přímo nebo nepřímo hmyzem či požitím znečištěné vody); antropozoonóza. Onemocnění vyvolává bakterie FRANCISELLA TULARENSIS (dř. Pasteurella). Podle způsobu proniknutí bakterie do organismu se rozlišuje forma ulceroglandulární (kožní léze – papula, později pustula a vřed s reakcí uzlin; nejčastější forma), okuloglandulární (průnik spojivkou), tyfoidní, plicní (pneumonie), glandulární (regionální lymfadenopatie) a střevní. Inkubace je 1–10 dnů, obv. do 5 dnů. Bývají celkové příznaky, obv. vysoké horečky, někdy exantém, histologicky granulomatózní zánět s nekrózou (urč. podobnost s tuberkulózou), mízní uzliny mohou zhnisat a perforovat. Diagnostika je mikrobiologická a sérologická. Léčí se antibiotiky (kombinace doxycyklinu s gentamicinem, chloramfenikol, cefalosporiny 3. generace); dále podle formy. Existuje vakcína. (cit. Velký lékařský slovník online, 2012 http://lekarske.slovniky.cz/ )
Definition (NCI) A serious Gram-negative bacterial infection caused by Francisella tularensis. It is transmitted to humans through bites from infected insects, inhaling airborne bacteria, handling infected animals, or consuming contaminated food or water. Signs and symptoms include skin ulcers, mouth sores, lymphadenopathy, sore throat, fever and pneumonia.
Definition (MSH) A plague-like disease of rodents, transmissible to man. It is caused by FRANCISELLA TULARENSIS and is characterized by fever, chills, headache, backache, and weakness.
Definition (CSP) disease caused by Francisella tularensis and transmitted to man from rodents through the bite of a deer fly, Chrysops discalis, and other bloodsucking insects; symptoms consist of a prolonged fever and often swelling of the lymph nodes; rabbits are important reservoir hosts.
Concepts Disease or Syndrome (T047)
MSH D014406
ICD9 021.9, 021
ICD10 A21 , A21.9
SnomedCT 266183001, 187300009, 186300002, 154297002, 19265001
LNC LA10514-0
English Tularemia, Tularemias, Unspecified tularemia, TULAREMIA, Tularaemia NOS, Tularaemia, unspecified, Tularemia, unspecified, [X]Tularaemia, unspecified, [X]Tularemia, unspecified, tularemia, tularemia (diagnosis), Francisella tularensis infection, Tularemia NOS, rabbit fever, deer-fly fever, Tularemia [Disease/Finding], Infections, Francisella tularensis, Francisella tularensis Infection, Infection, Francisella tularensis, Francisella tularensis Infections, fever rabbit, deerfly fever, tularemias, fever rabbits, Tuluremia, Tuluraemia, [X]Tularemia, unspecified (disorder), Tularemia NOS (disorder), Unspecified tularaemia, Francis' disease, Ohara's disease, Rabbit fever, Deer fly fever, Infection by Francisella tularensis, Pahvant Valley fever, Pahvant Valley plague, Yatobyo, Deerfly fever, O'Hara's disease, Tularaemia, Tularemia (disorder), Francisella tularensis; infection, Francis, Ohara, Pasteurella; infection, tularensis, deer fly; fever, fever; deer fly, fever; rabbit, infection; Francisella tularensis, infection; Pasteurella, tularensis, rabbit; fever, Tularemia, NOS, Tularaemia, NOS, tularaemia
Dutch Francisella tularensis-infectie, niet-gespecificeerde tularemie, Francisella tularensis; infectie, Pasteurella; infectie, tularensis, deer fly; fever, fever; deer fly, fever; rabbit, infectie; Francisella tularensis, infectie; Pasteurella, tularensis, rabbit; fever, Tularemie, niet gespecificeerd, tularemie, Tularemie
French Tularémie non précisée, Maladie d'Ohara, Infection à Francisella tularensis, Maladie de Francis, Pseudopeste, Tularémie, Fièvre de la mouche du cerf, Pseudo-peste
German unspezifische Tularaemie, Tularaemie ohne weitere Angabe, Francisella tularensis-Infektion, Tularaemie, nicht naeher bezeichnet, Tularaemie, Tularämie
Italian Tularemia non specificata, Infezione da Francisella tularensis, Tularemia
Portuguese Tularemia NE, Tularemia não especificada, Infecção por Francisella tularensis, Tularemia
Spanish Tularemia no especificada, Tularemia de localización indeterminada, Infección por Francisella tularensis, tularemia, SAI, [X]tularemia, no especificada, tularemia, SAI (trastorno), [X]tularemia, no especificada (trastorno), enfermedad de Ohara, fiebre de las moscas de los ciervos, fiebre de los conejos, fiebre del valle de Pahvant, infección por Francisella tularensis, peste del valle de Pahvant, tularemia (trastorno), tularemia, yatobyo, Tularemia
Japanese 野兎病, 野兎病菌感染, 詳細不明の野兎病, ﾔﾄﾋﾞｮｳｷﾝｶﾝｾﾝ, ｼｮｳｻｲﾌﾒｲﾉﾔﾄﾋﾞｮｳ, ﾔﾄﾋﾞｮｳ, ﾉｳｻｷﾞﾋﾞｮｳｷﾝｶﾝｾﾝ
Swedish Harpest
Finnish Tularemia
Russian TULIAREMIIA, ТУЛЯРЕМИЯ
Czech Infekce Francisella tularensis, Blíže neurčená tularemie, Tularemie, infekce Francisella tularensis, zaječí nemoc, tularemie, tularémie, zaječí mor
Korean 상세불명의 야생토끼병, 야생토끼병
Croatian TULAREMIJA
Polish Zakażenie Pasteurella tularensis, Tularemia
Hungarian Nem meghatározott tularaemia, Tularaemia, Francisella tularensis fertőzés, tularaemia
Norwegian Tularemi, Hjortefluefeber, Harepest, Infeksjoner som skyldes Francisella tularensis
Derived from the NIH UMLS (Unified Medical Language System)

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