Francisella tularensis

• Zoonontic infection carried on rodents and rabbits and transmitted by biting insects
• Presentation depends on route of entry: (ulcero)glandular, oculoglandular, pharyngeal, typhoidal, or pneumonic
• Treatment is streptomycin

Background

Microbiology

• A fastidious Gram-negative coccobacillus
• Multiple subspecies, including tularensis, holarctica, novocida, mediasiatica, and related species Francisella philomiragia and Francisella hispaniensis

History

• Discovered in 1911 in Tulare county, California
• Many names: deer fly fever, rabbit fever, etc...

Epidemiology

• Zoonotic infection whose main animal reservoirs are rodents and rabbits
  • In North America, the most important reservoirs are Sylvilagus species (especially Sylvilagus nuttalii, the cottontail rabbit) and Lepus species lagomorphs (rabbits), and a number of rodents including voles, squirrels, muskrats, and beavers
  • In Europe, the reservoirs include voles, hamsters, mice, and hares
• Essentially worldwide Northern Hemisphere distribution, especially in the US, Japan, Russia, and Scandinavian countries
• Transmission:
  • Vector-borne
    • In North America, by Amblyomma americanum ticks, Dermacentor variabilis ticks, Dermacentor andersoni ticks, Chrysops discalis deer flies
    • In Europe, Aedes cinereus and Ochlerotatus exrucians mosquitoes are more important, as well as Chrysops relictus deer flies and Haematopota pluvialis horse flies
  • Direct contact with animal products, including skinning, dressing, and eating wild game
  • Inhalation of aerosolized vectors (e.g. lawn-mowing), contact with contaminated water or mud, and animal bites of animals that have killed infected reservoir hosts (e.g. cats killing rodents)

Clinical Manifestations

• Ulceroglandular: ulcer develops at site of inoculation with tender lymphadenopathy and systemic symptoms
• Glandular: ulcer is undetectable or healed, only lymphadenopathy and systemic illness remains
• Oculoglandular: entry through the conjuctiva
• Pharyngeal: entry through the oropharynx, with exudative pharyngitis/tonsillitis
• Typhoidal: febrile illness without lymphadenopathy or ulcer, sometimes with diarrhea; patient often has an underlying chronic disease
• Pneumonic: direct inhalation, often from sheep shearing, landscaping, and microbiology laboratory work

Diagnosis

• Culture
  • Grows slowly on standard culture media, needs cystine-rich media (e.g. chocolate agar, BHI, or cystine media)
  • Looks bacillary in logarithmic growth phase (small Gram-negative rod), slow-growing only on chocolate agar
• Serology (EIA) can be used in the right context
• PCR

Management

• For severe disease, streptomycin 10 mg/kg (max 1 g) IM q12h for 7 to 10 days
  • Alternatives include gentamicin or amikacin
• For mild to moderate disease, alternatives include:
  • Doxycycline 100 mg po bid for 14 to 21 days
  • Ciprofloxacin 500 mg po bid for 10 to 14 days
• For meningitis, use an aminoglycoside (as above) plus either IV ciprofloxacin, doxycycline, or chloramphenicol for 14 to 21 days
  • Aminoglycosides have poor CNS penetration