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 gram-negative non-motile coccobacillus
  2. Carriers of F. tularensis
    1. Mammals
      1. Rabbits
      2. Wild rodents
    2. Deer Fly (Chrysops discalis)
    3. Tick Vector
      1. Amblyomma americanum (Lone star tick)
      2. Dermacentor variabilis (Dog tick)
  3. Transmission
    1. Tick Bite (accounts for 50% of U.S. cases)
    2. Risk of exposure as Biological Weapon
    3. Contaminated water ingestion
    4. Skin contact with infected animals
  4. Incubation: 1 to 14 days

IV. Symptoms: Constitutional (follows 3-5 day incubation)

  1. Fever and chills
  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. Glandular Type
    1. Localized, tender Lymphadenopathy
      1. Children: Cervical and occipital lymph nodes
      2. Adults: Inguinal lymph nodes
  2. Ulceroglandular Type (most common)
    1. Lymphadenopathy as in Glandular type
    2. Painful Skin Ulcer in region of Lymphadenopathy
  3. Oculoglandular Type
    1. 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
    2. Lymphadenopathy as in Glandular type above
      1. Preauricular, Submandibular, and Cervical nodes
  4. Pharyngeal Type
    1. Exudative Pharyngitis with severe Sore Throat
    2. Lymphadenopathy as in Glandular Type
      1. Cervical, pre-parotid and retropharyngeal nodes
  5. Typhoidal Type
    1. No significant Lymphadenopathy
    2. Profuse watery Diarrhea
  6. Pneumonic Type
    1. Non-productive cough
    2. Substernal and Pleuritic Chest Pain
    3. Infiltrates may be seen on Chest XRay

VI. Labs

  1. Inflammatory markers normal
    1. Erythrocyte Sedimentation Rate (ESR) near normal
    2. Complete Blood Count
      1. White Blood Cell Count near normal
  2. Sputum or blood testing
    1. Sputum or Blood Direct fluorescent Antibody
    2. Sputum Culture or Blood Culture
  3. Tularemia Serology
    1. Confirms diagnosis at two weeks

VII. Management

  1. Mild Disease (high relapse rate with these agents)
    1. Ciprofloxacin (cartilage risk under age 18 years)
      1. Dose: 400 mg IV q12 hours for 14-21 days
      2. When improved convert to 750 mg oral twice daily
    2. Doxycycline (avoid under age 8 years)
      1. Dose: 100 mg oral or IV twice daily for 14 to 21 days
  2. 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 7-10 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
      2. Child: 2.5 mg/kg IM or IV every 8 hours
  3. Meningitis
    1. Gentamicin or Tobramycin (at dose above) AND
    2. Chloramphenicol 50-100 mg/kg/day divided q6 hours IV

VIII. 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

IX. 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

X. Prognosis

  1. Mortality <2%

XI. Resources

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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

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, ヤトビョウキンカンセン, ショウサイフメイノヤトビョウ, ヤトビョウ, ノウサギビョウキンカンセン
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