Francisella tularensis: Difference between revisions

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*A fastidious [[Stain::Gram-negative]] [[Cellular shape::coccobacillus]]
*A fastidious [[Stain::Gram-negative]] [[Cellular shape::coccobacillus]]
*Multiple subspecies, including ''tularensis'', ''holarctica'', ''novocida'', ''mediasiatica'', and related species ''Francisella philomiragia'' and ''Francisella hispaniensis''
*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


===History===
===History===
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***In Europe, [[Vector::Aedes cinereus]] and [[Vector::Ochlerotatus exrucians]] mosquitoes are more important, as well as [[Vector::Chrysops relictus]] deer flies and [[Vector::Haematopota pluvialis]] horse flies
***In Europe, [[Vector::Aedes cinereus]] and [[Vector::Ochlerotatus exrucians]] mosquitoes are more important, as well as [[Vector::Chrysops relictus]] deer flies and [[Vector::Haematopota pluvialis]] horse flies
**Direct contact with animal products, including skinning, dressing, and eating wild game
**Direct contact with animal products, including skinning, dressing, and eating wild game
***Viable in carcasses and dust for up to 136 days
**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)
**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)

=== Pathophysiology ===

* 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)
* [[Toll-like receptors|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]]


==Clinical Manifestations==
==Clinical Manifestations==


*Incubation period of [[Usual incubation period::3 to 5 days]] (range [[Incubation period 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 [[Causes::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 [[Causes::relative bradycardia]] (more common in US than Europe)
*These symptoms may remit and relapse, presenting as a subacute [[Causes::relapsing fever]] over weeks, with associated weight loss, deconditioning, and lymphadenopathy
*'''Ulceroglandular:''' ulcer develops at site of inoculation with tender lymphadenopathy and systemic symptoms
*'''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
*'''Glandular:''' ulcer is undetectable or healed, only lymphadenopathy and systemic illness remains
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**Aminoglycosides have poor CNS penetration
**Aminoglycosides have poor CNS penetration


== Prevention ==

=== Vaccination ===

* Live attenuated vaccine derived from ''holarctica''

=== Lab Safety ===

* This is a [[Biosafety risk groups|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
* Commonly misidentified by automated methods as [[Haemophilus species|Haemophilus]] or [[Aggregatibacter]] species
{{DISPLAYTITLE:''Francisella tularensis''}}
{{DISPLAYTITLE:''Francisella tularensis''}}
[[Category:Gram-negative bacilli]]
[[Category:Gram-negative bacilli]]

Revision as of 08:56, 3 September 2020

  • 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, 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

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:

Pathophysiology

  • 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

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
  • 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
  • For mild to moderate disease, alternatives include:
  • For meningitis, use an aminoglycoside (as above) plus either IV ciprofloxacin, doxycycline, or chloramphenicol for 14 to 21 days
    • Aminoglycosides have poor CNS penetration

Prevention

Vaccination

  • Live attenuated vaccine derived from holarctica

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
  • Commonly misidentified by automated methods as Haemophilus or Aggregatibacter species