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

• 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