Francisella tularensis - Tularemia

Diagnosis

Indications for Testing

  • A history of contact with rabbits, ticks, dogs, cats, or skunks along with nonspecific febrile illness with prominent lymphadenopathy
  • Negative history of animal contact does not rule out diagnosis

Laboratory Testing

  • Serology – may require acute and convalescent phase titers
    • Preferred means of confirmation; retrospective in nature
    • Fourfold increase between acute and convalescent serology or >1:160 on acute titer
    • Cross-reactivity between Brucella, Salmonella, Yersinia, and Legionella antigens
  • 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 (respiratory specimens, blood, or exudate) can be sent for PCR
  • Consider testing for other disorders such as Rickettsia rickettsii (Rocky Mountain spotted fever), Rickettsia typhi (typhus fever), Brucella spp, Pasteurella multocida (pasteurellosis)

Imaging Studies

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

Differential Diagnosis

Clinical Background

Francisella tularensis is a cause of potentially severe zoonotic disease in humans. It is sometimes referred to as rabbit fever or deer-fly fever.

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, contact with infected animals via inapparent abrasions, 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 found predominantly in U.S.
      • Type B found predominantly in Europe and Asia
    • F. tularensis subsp. novicida (type C) – low-virulence strain in North America

Clinical Presentation

  • Incubation is generally 2-10 days
  • Disease often begins with the sudden onset of flu-like symptoms, including chills, fever, headache, 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
      • Progresses to fever, chills, myalgia, possibly septicemia
    • Oculoglandular (2-5%) – Parinaud syndrome
      • Direct contact with animal 
      • Conjunctival entry via contaminated fingers, splashes, aerosols
      • Unilateral intense conjunctivitis, preauricular, submandibular, cervical lymphadenopathy
        • Sequelae of corneal perforation and iris prolapse
    • 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 (typically ulceroglandular form)
      • Pneumonia with dry 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 or pneumonic 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 necessary and generally started prior to confirmation of disease
    • Relapses may occur with certain therapies
  • Vaccination available for at-risk individuals

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
Test Name and Number Recommended Use Limitations Follow Up
Francisella tularensis Antibodies, IgG and IgM 2005350
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Diagnose F. tularensis as agent of infection

Cross-reactions with Brucella or Yersinia antibodies may occur; results should be interpreted with caution and correlated with clinical information; the best evidence for current infection is significant change on two appropriately timed specimens

Convalescent titers 10-14 days may be necessary to confirm disease
Additional Tests Available
 
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
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: Identification. Methods may include biochemical, mass spectrometry, or sequencing.

If suspected, notify laboratory to rule out F. tularensis

For suspected agents of bioterrorism, notify state department of health and refer isolates to state laboratory for identification

Susceptibilities on agents of bioterrorism are not performed at ARUP
Rickettsia typhi (Typhus Fever) Antibody, IgM by IFA 0050383
Method: Semi-Quantitative Indirect Fluorescent Antibody
Rickettsia rickettsii (Rocky Mountain Spotted Fever) Antibody, IgG 0050369
Method: Semi-Quantitative Indirect Fluorescent Antibody
Brucella Antibody (Total) by Agglutination 0050135
Method: Semi-Quantitative 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
Francisella tularensis Antibody, IgG 2005353
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Cross-reactions with Brucella or Yersinia antibodies may occur; results should be interpreted with caution and correlated with clinical information; the best evidence for current infection is significant change on two appropriately timed specimens
Francisella tularensis Antibody, IgM 2005354
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Cross-reactions with Brucella or Yersinia antibodies may occur; results should be interpreted with caution and correlated with clinical information; the best evidence for current infection is significant change on two appropriately timed specimens