Francisella tularensis - Tularemia

Clinical Background

Francisella tularensis is a cause of potentially severe zoonotic disease in humans.

Epidemiology

• Incidence – <1/100,000 in U.S.
  • Most cases occur in the west central and mountain regions (56% of total cases from 1990 – 2000 occurred in Arkansas, Oklahoma, Missouri, and South Dakota)
• Transmission – blood-sucking arthropods or contact with infected animals via inapparent abrasions or consumption of contaminated water
  • Primarily a disease of wild animals, especially rabbits
  • In U.S., human vectors are primarily ticks and deer flies
    • Tick vectors include Amblyomma americanum, Dermacentor andersoni, Dermacentor variabilis
  • Peak seasons – spring and summer
    • Historical peaks during fall and early winter (hunting season)

Organism

• Gram-negative, aerobic, non-spore forming, fastidious coccobacillus
  • Two main biovars are F. tularensis subsp. tularensis (type A) and F. tularensis subsp. holarctica (formerly subsp. palearctica, type B)
    • Type A is found predominantly in the U.S.
    • Type B is found predominantly in Europe and Asia
  • F. tularensis subsp. novicida (type C) is a low-virulence strain in North America

Clinical Presentation

• Incubation is generally 2-10 days
• The disease often begins with the sudden onset of flu-like symptoms, including chills, fever, headache and generalized aches
• Forms of tularemia
  • Ulceroglandular (21-85%)
    • Direct contact with animal or insect bite
    • Most common form of tularemia
    • Starts as small, painful papule that becomes an ulcer at entry portal with associated lymphadenopathy (glandular tularemia [3-20%] similar presentation but lacking ulcer)
  • Oculoglandular (2-5%)
    • Direct contact with animal 
    • Conjunctival (entry via contaminated fingers, splashes, aerosols)
    • Unilateral intense conjunctivitis, preauricular, submandibular, cervical lymphadenopathy
  • Oropharyngeal and gastrointestinal (2-12%)
    • Follows ingestion of contaminated food or water
    • Oral – exudative pharyngitis; deep, cervical lymphadenopathy
    • Gastrointestinal – ulcerative GI lesions, diarrhea
  • Pneumonic (8-20%)
    • Inhalational exposure or extension from systemic disease
    • Pneumonia with cough, pleuritic chest pain
    • Often occupational exposure (sheep shearing, animal husbandry, farming, lawn/brush cutting, laboratory workers)
  • Typhoidal (5-30%)
    • Rare in U.S.
    • Usually associated with bacteremic gastrointestinal disease and consumption of poorly cooked wild game
    • High fever, headache, diarrhea shock
• Complications – septicemia, meningitis, endocarditis, hepatitis, renal failure

Treatment and Prevention

• Antibiotic treatment is necessary, but relapses may occur with certain therapies
• Vaccination available for at-risk individuals

Diagnosis

Indications for Testing

• A history of contact with rabbits, ticks, dogs, cats or skunks is suggestive, but a negative history of animal contact does not rule out diagnosis

Laboratory Testing

• Serology – may require acute and convalescent phase titers
  • Preferred means of confirmation
  • 4-fold increase between acute and convalescent serology or >1:160 on acute titer
• Culture – frequently negative
  • Difficult to culture – fastidious organism
  • Select agents; confirmed positive culture requires approval before transfer
• PCR – not widely available but very sensitive
  • Tissue samples can be sent for PCR

Imaging Studies

• Chest x-ray for patients presenting with signs and symptoms of pneumonia; demonstrates infiltrates

Differential Diagnosis

• Ulceroglandular
  • Streptococcal/staphylococcal skin infection
    • Staphylococcal disease
    • Streptococcal disease, Group B
  • Anthrax
  • Pasteurellosis
  • Atypical mycobacteria
  • Human immunodeficiency virus (HIV)
  • Cytomegalovirus
  • Epstein-Barr virus 
  • Rickettsia
    • Rickettsia rickettsii  (Rocky Mountain spotted fever)
    • Rickettsia typhi  (typhus fever)
  • Plague
  • Lymphoma
    • B-cell lymphoma
• Pneumonic 
  • Hantavirus
  • Influenza virus
  • Mycoplasma pneumoniae
  • Brucella species
  • Legionella pneumophila
  • Anthrax
  • Severe acute respiratory syndrome
  • Chlamydophila pneumoniae or psittaci
  • Coxiella burnetii (Q–fever)
  • Mycobacterium tuberculosis
  • Acute respiratory distress syndrome
  • Streptococcus pneumoniae
  • Respiratory syncytial virus
• Oropharyngeal
  • Streptococcal disease, Group A
  • Mononucleosis
  • HIV
• Typhoidal
  • Sepsis
• Oculoglandular
  • Viral or bacterial conjunctivitis

Indications for Laboratory Testing

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
Organism Identification by 16S rDNA Sequencing 0060720 Method: 16S rDNA Sequencing	If suspected, notify laboratory to rule out F. tularensis
Aerobic Organism Identification 0060115 Method: Standard reference procedures for aerobic bacterial identification and/or 16s rDNA sequencing for select bacterial isolates.	If suspected, notify laboratory to rule out F. tularensis
Rickettsia typhi (Typhus Fever) Antibody, IgM by IFA 0050383 Method: Indirect Fluorescent Antibody
Rickettsia rickettsii (Rocky Mountain Spotted Fever) Antibody, IgG 0050369 Method: Indirect Immunofluorescence Assay
Brucella Antibody (Total) by Agglutination 0050135 Method: Bacterial Agglutination	Cross-reactions may occur between Brucella and F.tularensis antigens and antisera; therefore, parallel tests should be run with these antigens; a fourfold rise in titer is considered diagnostic