Francisella tularensis - Tularemia

Francisella tularensis causes potentially severe zoonotic disease in humans. It is sometimes referred to as rabbit fever or deer-fly fever. Serology is the preferred means of confirmation. Clinicians may want to consider testing for other similar disorders, including Rickettsia rickettsii (Rocky Mountain spotted fever), Rickettsia typhi (typhus fever), Brucella spp, and Pasteurella multocida (pasteurellosis).

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

  • CDC diagnostic testing for tularemia
  • Serology – 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
  • Consider testing for other disorders such as Rickettsia rickettsii (Rocky Mountain spotted fever), Rickettsia typhi (typhus fever), Brucella spp, and Pasteurella multocida (pasteurellosis)

Imaging Studies

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

Differential Diagnosis

Background

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, airborne spread of contaminated materials
    • Primarily a disease of wild animals, especially rabbits
    • Risk groups – farmers, veterinarians, hunters, landscapers, meat handlers, lab workers
    • 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, nonspore 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

  • Average incubation – 3-5 days (range 1-21 days)
  • Disease often begins with the sudden onset of flu-like symptoms, including chills, fever, headache, generalized aches
  • Forms of tularemia (mostly depends on portal of entry)
    • Ulceroglandular
      • Most common form in adults
      • Direct contact with animal or insect bite
      • Starts as small, painful papule that becomes an ulcer at entry portal with associated lymphadenopathy
    • Glandular – similar presentation to ulceroglandular but lacking ulcer
      • Most common form in children
      • Progresses to fever, chills, myalgia, possibly septicemia
    • Oculoglandular – Parinaud syndrome
      • Conjunctival entry via contaminated fingers, splashes, aerosols
      • Unilateral intense conjunctivitis, preauricular, submandibular, cervical lymphadenopathy
        • Sequelae of corneal perforation and iris prolapse
    • Oropharyngeal and gastrointestinal
      • Ingestion of contaminated food or water
      • Oral – exudative pharyngitis; deep, cervical lymphadenopathy
      • Gastrointestinal – ulcerative gastrointestinal lesions, diarrhea
    • Pneumonic
      • Inhalational exposure or extension from systemic disease (typically ulceroglandular form)
      • Pneumonia with dry cough and pleuritic chest pain
      • Often occupational exposure (sheep shearing, animal husbandry, farming, lawn/brush cutting, laboratory workers)
    • Typhoidal
      • Rare in U.S.
      • May occur from any portal of entry
        • Usually associated with bacterial gastrointestinal or pneumonic disease and consumption of poorly cooked wild game
      • High fever, headache, diarrhea, sore throat, anorexia
  • Complications – septicemia, meningitis, endocarditis, hepatitis, renal failure

ARUP Lab Tests

Preferred test for detecting antibodies during acute or convalescent phase

Convalescent sera may be required for diagnosis

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

Repeat testing in 10-14 days may be helpful if results are equivocal

Related Tests

Reference method for identification of most bacterial species

Identify aerobic bacterial isolates

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

For identification by 16s rDNA sequencing only, refer to organism identification by 16s rDNA sequencing; for identification AND susceptibility testing, refer to aerobic organism identification with reflex to susceptibility

Confirm presence of Rickettsia typhi

Panel test (IgG and IgM) is preferred

Require comparison of acute- to convalescent-phase serology

Detects antibodies during convalescent phase

Recommended serology test to detect recent infection from Brucella in the context of a clinically compatible illness and exposure history

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

Detects antibodies during convalescent phase

Convalescent sera may be required for diagnosis

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

Detects antibodies during acute phase; paired concurrent specimen with IgG reduces false-positive rate

Convalescent sera may be required for diagnosis

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

Medical Experts

Contributor

Couturier

Marc Roger Couturier, PhD, D(ABMM)
Associate Professor of Clinical Pathology, University of Utah
Medical Director, Parasitology/Fecal Testing, Infectious Disease Antigen Testing, Bacteriology, and Molecular Amplified Detection, ARUP Laboratories

References

Additional Resources
  • 18755386

    Nigrovic LE, Wingerter SL. Tularemia. Infect Dis Clin North Am. 2008; 22 (3): 489-504, ix.
    PubMed