Francisella tularensis

From IDWiki
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



  • A fastidious Gram-negative coccobacillus
    • Very small on Gram stain, giving a "pink sand" appearance
    • Do not stain well; fuchsine dye can help
    • Needs cysteine to grow, so doesn't grow well on normal media
  • Weakly catalase positive, usually oxidase negative, and urease negative
  • Multiple subspecies, including tularensis, holarctica, novocida, mediasiatica, which are further subdivided into clades, and related species Francisella philomiragia and Francisella hispaniensis
  • Subspecies of importance to humans include:
    • Subspecies tularensis (type A strains)
      • Found in North America and rarely Europe
      • Two major clades (AI and AII) and four subclades (AIa, AIb, AIIa, and AIIb)
      • Overall the subspecies is the most virulent subspecies, and specifically the AIb subclade is the most virulent strain
    • Subspecies holarctica (type B strains)
      • Found in the entire northern hemisphere as well as Australia
      • Four major clades (B4 in North America, B6 in Western Europe, B12 in Eastern Europe and Central Asia, and B16 in Japan and other areas in Eastern Asia) and a number of subclades
    • Subspecies novicida
      • Rare cause of disease in humans, usually in immunocompromised hosts, and presents with bacteremia rather than tularemia
    • Subspecies mediasiatica does not cause disease in humans


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


  • Zoonotic infection whose main animal reservoirs are rodents and rabbits
    • In North America, the most important reservoirs are Sylvilagus (especially Sylvilagus nuttalii, the cottontail rabbit) and Lepus lagomorphs (rabbits), and a number of rodents including voles, squirrels, muskrats (especially in Canada), 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
    • In Canada, occurs mostly in the Prairies
  • Transmission through a number of mechanisms


  • Infectious dose depends on route, but is as low as 10 to 50 organisms when injected intradermally or inhaled (or several orders of magnitude higher if ingested)
  • TLR4 has less affinity for its LPS compared to other bacteria
  • Capsule inhibits IgM and complement C3
    • Capsule-deficient strains are both less immunogenic and less virulent
  • Facultative intracellular growth
    • Can infect and persist within erythrocytes, providing protection against aminoglycosides

Virulence Factors

  • Lipopolysaccharide is not well-recognized by TLR4
  • Capsule
  • Type IV pili binds to epithelial cells
  • Facultatively intracellular

Clinical Manifestations

  • Incubation period of 3 to 5 days (range 1 to 21 days)
  • The first symptom is usually a papule at the site of inoculation that develops into an ulcer over 1 to 2 days, but this may go unnoticed
  • This is followed by fever which likely corresponds to initial lymphohematogenous dissemination
    • Other common symptoms include chills, headache, malaise, anorexia, and fatigue
    • May also have cough, myalgias, chest discomfort, vomiting, sore throat, abdominal pain, and diarrhea
    • May have a relative bradycardia (more common in US than Europe)
  • These symptoms may remit and relapse, presenting as a subacute relapsing fever over weeks, with associated weight loss, deconditioning, and lymphadenopathy
  • Bloodwork may show leukocytosis and elevated ESR, as well as occasional thrombocytopenia, hyponatremia, elevated liver enzymes, elevated CK, myoglobinuria, and sterile pyuria

Ulceroglandular Tularemia

  • Most common
  • Ulcer develops at site of inoculation with tender lymphadenopathy and systemic symptoms
  • Ulcer can be red papule or vesicular (similar to HSV), then either heals or becomes necrotic

Glandular Tularemia

  • Ulcer is undetectable or healed, only lymphadenopathy and systemic illness remains

Oculoglandular Tularemia

  • Entry through the conjuctiva
  • Rare

Pharyngeal Tularemia

  • Entry through the oropharynx, with exudative pharyngitis/tonsillitis
  • May be difficult to distinguish from other forms of tularemia that also may have sore throat

Typhoidal Tularemia

  • Febrile illness without lymphadenopathy or ulcer, sometimes with diarrhea
  • May involve endocarditis
  • Patient often has an underlying chronic disease
  • Often rapidly-progressive and fatal

Pneumonic Tularemia

  • Acquired by direct inhalation, often from sheep shearing, landscaping, and microbiology laboratory work
  • Can also develop secondary to one of the other syndromes
  • Chest x-ray is non-specific

Complications and Prognosis

  • Suppurative lymphadenopathy is the most common complication despite antibiotics, and may require drainage
  • Severe disease may cause DIC, renal failure, rhabdomyolysis, jaundice, and hepatitis
  • Without treatment, complications include meningitis, encephalitis, pericarditis, peritonitis, osteomyelitis, splenic rupture, and thrombophlebitis
  • Rarely, Guillain-Barré syndrome following ulceroglandular tularemia
  • Symptoms, especially neuropsychiatric symptoms, may persist for weeks after treatment
  • Mortality is 60% without treatment, and decreases to 2 to 4% with antibiotics


  • Diagnosis is primarily clinical, and treatment should be given while attempting to confirm with diagnostic testing


  • Notify lab that tularemia is suspected before sending samples
  • Gram stain is very rarely positive
  • May be isolated from blood, pleural fluid, lymph nodes, wounds, sputum, and gastric aspirates
  • 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


  • The most common test used to diagnose
  • Can use tube agglutination (used in Ontario and the US), microagglutination, hemagglutination, enzyme-linked immunosorbent assay (used in Europe), or immunochromatographic assay
  • IgM and IgG appear together, usually after 2 weeks and peak at 4 to 5 weeks
  • Can persist for at least 10 years
  • Presumptive positive with a single titre ≥1:160 (tube agglutination) or ≥1:128 (microagglutination), but this can also be compatible with remote infection
  • Definitive diagnosis is made with a four-fold rise in acute and convalescent serology collected 2 to 3 weeks apart, with at least one test being above the threshold for presumptive positive
  • May cross-react with Brucella, Proteus OX19, Legionella, and Yersinia, but titres normally aren't particularly high, as well as with environmental, non-pathogenic Francisella


  • DFA and PCR are available at reference labs
  • Slide agglutination of a colony as a rapid test to identify
  • Automated methods should not be used, due to the risk of aerosolization, and may also misindentify as Haemophilus or Aggregatibacter species




  • Live attenuated vaccine derived from holarctica

Post-Exposure Prophylaxis

Lab Safety

  • This is a biosafety risk group 3 organism
  • Should be suspected with any slowly-growing, small, and poorly-staining Gram-negative coccobacillus is isolated on chocolate agar but not blood agar
  • Automated laboratory identification systems should not be used, because the risk of aerosol generation