Francisella tularensis: Difference between revisions
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Francisella tularensis
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*A fastidious [[Stain::Gram-negative]] [[Cellular shape::coccobacillus]] |
*A fastidious [[Stain::Gram-negative]] [[Cellular shape::coccobacillus]] |
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*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'' |
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*Subspecies of importance to humans include: |
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**Subspecies ''tularensis'' (type A strains) |
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***Found in North America and rarely Europe |
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***Two major clades (AI and AII) and four subclades (AIa, AIb, AIIa, and AIIb) |
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***Overall the subspecies is the most virulent subspecies, and specifically the AIb subclade is the most virulent strain |
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**Subspecies ''holarctica'' (type B strains) |
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***Found in the entire northern hemisphere as well as Australia |
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***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 |
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**Subspecies ''novicida'' |
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***Rare cause of disease in humans, usually in immunocompromised hosts, and presents with bacteremia rather than tularemia |
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**Subspecies ''mediasiatica'' does not cause disease in humans |
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===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 |
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**Direct contact with animal products, including skinning, dressing, and eating wild game |
**Direct contact with animal products, including skinning, dressing, and eating wild game |
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***Viable in carcasses and dust for up to 136 days |
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**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) |
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=== Pathophysiology === |
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* 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) |
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* [[Toll-like receptors|TLR4]] has less affinity for its LPS compared to other bacteria |
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* Capsule inhibits IgM and complement C3 |
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** Capsule-deficient strains are both less immunogenic and less virulent |
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* Facultative intracellular growth |
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** Can infect and persist within erythrocytes, providing protection against [[aminoglycosides]] |
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==Clinical Manifestations== |
==Clinical Manifestations== |
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*Incubation period of [[Usual incubation period::3 to 5 days]] (range [[Incubation period range::1 to 21 days]]) |
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*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 |
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*This is followed by [[Causes::fever]] which likely corresponds to initial lymphohematogenous dissemination |
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**Other common symptoms include chills, headache, malaise, anorexia, and fatigue |
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**May also have cough, myalgias, chest discomfort, vomiting, sore throat, abdominal pain, and diarrhea |
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**May have a [[Causes::relative bradycardia]] (more common in US than Europe) |
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*These symptoms may remit and relapse, presenting as a subacute [[Causes::relapsing fever]] over weeks, with associated weight loss, deconditioning, and lymphadenopathy |
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*'''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 |
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*'''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 |
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== Prevention == |
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=== Vaccination === |
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* Live attenuated vaccine derived from ''holarctica'' |
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=== Lab Safety === |
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* This is a [[Biosafety risk groups|biosafety risk group]] 3 organism |
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* Should be suspected with any slowly-growing, small, and poorly-staining Gram-negative coccobacillus is isolated on chocolate agar but not blood agar |
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* Automated laboratory identification systems should ''not'' be used, because the risk of aerosol generation |
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* Commonly misidentified by automated methods as [[Haemophilus species|Haemophilus]] or [[Aggregatibacter]] species |
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{{DISPLAYTITLE:''Francisella tularensis''}} |
{{DISPLAYTITLE:''Francisella tularensis''}} |
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[[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
- Subspecies tularensis (type A strains)
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
- 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)
- Vector-borne
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
- 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
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