Coxiella burnetii: Difference between revisions

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Coxiella burnetii
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==Background==
βˆ’
= Coxiella burnetti =
  
  +
===History===
   
  +
*Originally described in Australia in 1935 among workers at a meatworks
βˆ’
== Summary ==
  
  +
*Q fever, for query fever, because the doctor suspected a new infection
   
  +
===Microbiology===
βˆ’
*
 
   
  +
*Highly pleomorphic, intracellular, spore-forming, Gram-negative coccobacillus that causes Q fever
βˆ’
== History ==
  
  +
**Enters cell passively
  +
*Phase variation, with two phases that differ in their lipopolysaccharides and some other characteristics
  +
**Phase I: state in nature
  +
*Related to rickettsiae
   
  +
===Epidemiology===
βˆ’
* Originally described in Australia in 1935 among workers at a meatworks
  
βˆ’
* Q fever, for query fever, because the doctor suspected a new infection
  
   
  +
*Zoonotic disease, most commonly of cattle, sheep, and goats
βˆ’
== Microbiology ==
  
  +
**Also infected peripartum cats
  +
**Maintained in a transmission cycle with ticks or other arthropods
  +
**Ungulates often asymptomatic
  +
**Can be detected in air up to 2 weeks post-partum and in soil for 6 months
  +
*Released by an infected animal during childbirth, though windborne spread can carry it at least 10 km
  +
**Placenta has an extremely high burden of bacteria
  +
**Can also be found in stool, urine, and milk
  +
**Unpasteurized milk
  +
*Inhaled by humans with an incubation period of [[Usual incubation period::20 days]] ([[Incubation period range::1 to 39 days]])
  +
**Dose-dependent incubation period
  +
**Chronic Q fever can be up to 6 months
  +
*Worldwide distribution, except New Zealand
  +
**Hepatitis more in Europe, pneumonia more in US
   
  +
===Risk Factors===
βˆ’
* Highly pleomorphic, intracellular, spore-forming, Gram-negative coccobacillus that causes Q fever
  
βˆ’
** Enters cell passively
  
βˆ’
* Phase variation, with two phases that differ in their lipopolysaccharides and some other characteristics
  
βˆ’
** Phase I: state in nature
  
βˆ’
* Related to rickettsiae
  
   
  +
*Working with or near animals, especially peripartum
βˆ’
== Epidemiology ==
  
  +
*Lab exposure
  +
*Unpasteurized milk
   
  +
===Pathophysiology===
βˆ’
* Zoonotic disease, most commonly of cattle, sheep, and goats
  
βˆ’
** Also infected peripartum cats
  
βˆ’
** Maintained in a transmission cycle with ticks or other arthropods
  
βˆ’
** Ungulates often asymptomatic
  
βˆ’
** Can be detected in air up to 2 weeks post-partum and in soil for 6 months
  
βˆ’
* Released by an infected animal during childbirth, though windborne spread can carry it at least 10 km
  
βˆ’
** Placenta has an extremely high burden of bacteria
  
βˆ’
** Can also be found in stool, urine, and milk
  
βˆ’
** Unpasteurized milk
  
βˆ’
* Inhaled by humans with an incubation period of 20 days (1 to 39 days)
  
βˆ’
** Dose-dependent incubation period
  
βˆ’
** Chronic Q fever can be up to 6 months
  
βˆ’
* Worldwide distribution, except New Zealand
  
βˆ’
** Hepatitis more in Europe, pneumonia more in US
  
   
  +
*Bacteria enter lungs, where they proliferate in the macrophages and invade the bloodstream
βˆ’
== Risk Factors ==
  
  +
**Lives in the phagolysosome
  +
**Can cause graulomas
  +
*Alternatively, can enter via tick bite or via ingestion
  +
*Invasion of bloodstream causes systemic symptoms, with severity depending on the dose inhaled
  +
*QPH1 is a more virulent strain
   
  +
==Clinical Manifestations==
βˆ’
* Working with or near animals, especially peripartum
  
βˆ’
* Lab exposure
  
βˆ’
* Unpasteurized milk
  
   
  +
*Can present as asymptomatic, self-limited febrile illness lasting 2 to 14 days (most common), pneumonia, or hepatitis
βˆ’
== Pathophysiology ==
  
  +
**Asymptomatic more common in pregnant women and children
  +
*Infective endocarditis, osteomyelitis, CNS infection including aseptic meningitis
  +
*Q fever in immunocompromised host, Q fever in infancy, Q fever in pregnancy
  +
*Post-Q fever fatigue syndrome
   
  +
===Acute Q fever===
βˆ’
* Bacteria enter lungs, where they proliferate in the macrophages and invade the bloodstream
  
βˆ’
** Lives in the phagolysosome
  
βˆ’
** Can cause graulomas
  
βˆ’
* Alternatively, can enter via tick bite or via ingestion
  
βˆ’
* Invasion of bloodstream causes systemic symptoms, with severity depending on the dose inhaled
  
βˆ’
* QPH1 is a more virulent strain
  
   
  +
*Fever is uniform finding in all syndromes
βˆ’
== Syndromes ==
  
  +
*Chills, headache (severe), fatigue, and myalgias that lasts 2-21 days (14)
  +
*Can present with rash including urticaria
  +
*Palpable purpura can be seen in chronic Q fever (that is, endocarditis)
   
  +
===Pneumonia===
βˆ’
* Can present as asymptomatic, self-limited febrile illness lasting 2 to 14 days (most common), pneumonia, or hepatitis
  
βˆ’
** Asymptomatic more common in pregnant women and children
  
βˆ’
* Infective endocarditis, osteomyelitis, CNS infection including aseptic meningitis
  
βˆ’
* Q fever in immunocompromised host, Q fever in infancy, Q fever in pregnancy
  
βˆ’
* Post-Q fever fatigue syndrome
  
   
  +
*Can present as an atypical pneumonia, a rapidly-progressing pneumonia, and an incidental pneumonia in a febrile patient (most common)
βˆ’
=== Acute Q fever ===
  
  +
*A community-acquired pneumonia that doesn't respond to first-line antibiotics (like Legionella and pneumonic tularemia)
  +
*Cough, though often not present, can be non-productive, productive, or bloody
  +
*More common in Americas than Europe
   
  +
===Hepatitis===
βˆ’
* Fever is uniform finding in all syndromes
  
βˆ’
* Chills, headache (severe), fatigue, and myalgias that lasts 2-21 days (14)
  
βˆ’
* Can present with rash including urticaria
  
βˆ’
* Palpable purpura can be seen in chronic Q fever (that is, endocarditis)
  
   
  +
*Three forms:
βˆ’
=== Pneumonia ===
  
  +
**An infectious hepatitis–like picture
  +
**Fever of unknown origin, with characteristic granulomas ("donut-like") on liver biopsy
  +
**An incidental finding in a patient with acute Q fever pneumonia
  +
*More common in Europe and Americas
   
  +
===CNS Infections===
βˆ’
* Can present as an atypical pneumonia, a rapidly-progressing pneumonia, and an incidental pneumonia in a febrile patient (most common)
  
βˆ’
* A community-acquired pneumonia that doesn't respond to first-line antibiotics (like Legionella and pneumonic tularemia)
  
βˆ’
* Cough, though often not present, can be non-productive, productive, or bloody
  
βˆ’
* More common in Americas than Europe
  
   
  +
*Can cause Miller-Fischer variant of Guillain-BarrΓ© syndrome
βˆ’
=== Hepatitis ===
  
   
  +
===Endocarditis===
βˆ’
* Three forms:
  
βˆ’
** An infectious hepatitis–like picture
  
βˆ’
** Fever of unknown origin, with characteristic granulomas ("donut-like") on liver biopsy
  
βˆ’
** An incidental finding in a patient with acute Q fever pneumonia
  
βˆ’
* More common in Europe and Americas
  
   
  +
*Subacute or chronic febrile illess
βˆ’
=== CNS infections ===
  
  +
*Clubbing and hepatosplenomegaly are common
  +
*Higher titres are more convincing β‰₯1:6400
   
  +
==Diagnosis==
βˆ’
* Can cause Miller-Fischer variant of Guillain-BarrΓ© syndrome
  
   
  +
*Not readily culturable (nor should you try), though you can see it with Giemsa stain
βˆ’
=== Endocarditis ===
  
  +
*PCR is possible though not common
  +
*Causes a false-positive RF, APLA
  +
*Main method of detection is serology
   
  +
===Serology===
βˆ’
* Subacute or chronic febrile illess
  
βˆ’
* Clubbing and hepatosplenomegaly are common
  
βˆ’
* Higher titres are more convincing β‰₯1:6400
  
   
  +
*Immunofluorescence assay is standard; no need for EIA
βˆ’
== Diagnosis ==
  
  +
*Two phases of IgG antibodies (phase I and II)
  +
**Phase II corresponds more to acute
  +
***Positive if IgM >50 and IgG >200, or if there's a 4x rise in either titres
  +
***Detectable by 2 weeks, should be positive by 4
  +
***Peak at 2 months, then decrease except the IgG in cases of endocarditis
  +
***Also IgA, but not clinically relevant
  +
**Phase I corresponds more to chronic
  +
***Can test for IgG (useful) and IgA (useless) titres
  +
***IgG β‰₯ 800 consistent with chronic infection, and is one of the minor Duke criteria for endocarditis
  +
***IgG β‰₯ 6400 is suggestive of endovascular infection or endocarditis (major criteria),
  +
*Two ways to diagnose acute infection
  +
**Retrospectively with a fourfold rise in both titres from acute to chronic stage, or
  +
**One-time phase II IgM >50 and IgG >2000
  +
*Chronic infection is diagnosed clinically, with a phase I IgG titre greater than the phase II IgG titre, and both are at least IgG titre >1:1600
  +
*IgM antibodies are usually undetectable by 4 months, though IgG may persist for more than a decade
   
  +
==Management==
βˆ’
* Not readily culturable (nor should you try), though you can see it with Giemsa stain
  
βˆ’
* PCR is possible though not common
  
βˆ’
* Causes a false-positive RF, APLA
  
βˆ’
* Main method of detection is serology
  
   
  +
*Acute Q fever
βˆ’
=== Serology ===
  
  +
**Consider screening for bicuspid valve with TTE if high risk, or baseline TTE
  +
**[[Doxycycline]] 100mg po bid x 10-14 days
  +
**Second-line is [[fluoroquinolones]] or [[macrolides]]
  +
**Consider monitoring titres for some period afterwards
  +
**In patients with prosthetic heart valves, consider prolonged treatment as per chronic Q fever (like 1 year)
  +
*Chronic Q fever
  +
**Definitely screen for [[endocarditis]]
  +
**[[Doxycycline]] + [[hydroxychloroquine]] 200mg/d continued until phase I IgG titres have decreased to ≀1:800
  +
***[[Hydroxychloroquine]] potentiates [[doxycycline]] in the phagolysosomes (makes the doxycycline bactericidal)
  +
***Monitor for ophthalmologic complications, and both have photosensitivity
  +
***Can adjust dose of [[hydroxychloroquine]] to target serum level 0.8 to 1.2 mcg/mL
  +
**Duration 1.5 years for native valve [[endocarditis]], 2 years for [[prosthetic valve endocarditis]]
  +
**Measure titres every 3-6 months during treatment, then every 3 months for 2 years after completing treatment
   
  +
===Pregnancy===
βˆ’
* Immunofluorescence assay is standard; no need for EIA
  
βˆ’
* Two phases of IgG antibodies (phase I and II)
  
βˆ’
** Phase II corresponds more to acute
  
βˆ’
*** Positive if IgM >50 and IgG >200, or if there's a 4x rise in either titres
  
βˆ’
*** Detectable by 2 weeks, should be positive by 4
  
βˆ’
*** Peak at 2 months, then decrease except the IgG in cases of endocarditis
  
βˆ’
*** Also IgA, but not clinically relevant
  
βˆ’
** Phase I corresponds more to chronic
  
βˆ’
*** Can test for IgG (useful) and IgA (useless) titres
  
βˆ’
*** IgG β‰₯ 800 consistent with chronic infection, and is one of the minor Duke criteria for endocarditis
  
βˆ’
*** IgG β‰₯ 6400 is suggestive of endovascular infection or endocarditis (major criteria),
  
βˆ’
* Two ways to diagnose acute infection
  
βˆ’
** Retrospectively with a fourfold rise in both titres from acute to chronic stage, or
  
βˆ’
** One-time phase II IgM >50 and IgG >2000
  
βˆ’
* Chronic infection is diagnosed clinically, with a phase I IgG titre greater than the phase II IgG titre, and both are at least IgG titre >1:1600
  
βˆ’
* IgM antibodies are usually undetectable by 4 months, though IgG may persist for more than a decade
  
   
  +
*''Coxiella'' loves the placenta
βˆ’
== Management ==
  
  +
*It can be a cause of flu-like illness in pregnant women with a potential exposure history
  +
**This can be associated with first-trimester pregnancy loss
  +
*[[Doxycycline]] and [[fluoroquinolones]] are contraindicated
  +
*[[TMP-SMX]] 1600/320 daily, make sure they're on folic acid supplementation
  +
**Continue it for the duration of pregnancy
  +
**Theoretic risk of [[hyperbilirubinemia]] in third trimester, so may consider holding it towards the end unless there's documented chronic infection
  +
*High risk of developing chronic infection, so titres should be monitored for at least 2 years
  +
**If persistent IgG > 800, consider TEE
   
  +
==Prevention==
βˆ’
* Acute Q fever
  
βˆ’
** Consider screening for bicuspid valve with TTE if high risk, or baseline TTE
  
βˆ’
** Doxycyxline 100mg po bid x 10-14 days
  
βˆ’
** Second-line is fluoroquinolones or macrolides
  
βˆ’
** Consider monitoring titres for some period afterwards
  
βˆ’
** In patients with prosthetic heart valves, consider prolonged treatment as per chronic Q fever (like 1 year)
  
βˆ’
* Chronic Q fever
  
βˆ’
** Definitely screen for endocarditis
  
βˆ’
** Doxycycline + hydroxychloroquine 200mg/d continued until phase I IgG titres have decreased to ≀1:800
  
βˆ’
*** Hydroxychloroquine potentiates doxycycline in the phagolysosomes (makes the doxy bactericidal)
  
βˆ’
*** Monitor for ophthalmologic complications, and both have photosensitivity
  
βˆ’
*** Can adjust dose of hydroxychloroquine to target serum level 0.8 to 1.2 mcg/mL
  
βˆ’
** Duration 1.5 years for native valve endocarditis, 2 years for prosthetic valve endocarditis
  
βˆ’
** Measure titres every 3-6 months during treatment, then every 3 months for 2 years after completing treatment
  
   
  +
*Vaccinate high-risk workers
βˆ’
== Considerations in Pregnancy ==
  
   
βˆ’
* ''Coxiella'' loves the placenta
 +
{{DISPLAYTITLE:''Coxiella burnetii''}}
  +
[[Category:Rickettsioses]]
βˆ’
* It can be a cause of flu-like illness in pregnanct women with a potential exposure history
  
βˆ’
** This can be associated with first-trimester pregnancy loss
  
βˆ’
* Doxycycline and fluoroquinolones are contraindicated
  
βˆ’
* Septra 1600/320 daily, make sure they're on folic acid supplementation
  
βˆ’
** Continue it for the duration of pregnancy
  
βˆ’
** Theoretic risk of hyperbilirubinemia in third trimester, so may consider holding it towards the end unless there's documented chronic infection
  
βˆ’
* High risk of developing chronic infection, so titres should be monitored for at least 2 years
  
βˆ’
** If persistent IgG > 800, consider TEE
  
βˆ’  
βˆ’
== Prevention ==
  
βˆ’  
βˆ’
* Vaccinate high-risk workers
  

Latest revision as of 15:05, 13 July 2022

Background

History

  • Originally described in Australia in 1935 among workers at a meatworks
  • Q fever, for query fever, because the doctor suspected a new infection

Microbiology

  • Highly pleomorphic, intracellular, spore-forming, Gram-negative coccobacillus that causes Q fever
    • Enters cell passively
  • Phase variation, with two phases that differ in their lipopolysaccharides and some other characteristics
    • Phase I: state in nature
  • Related to rickettsiae

Epidemiology

  • Zoonotic disease, most commonly of cattle, sheep, and goats
    • Also infected peripartum cats
    • Maintained in a transmission cycle with ticks or other arthropods
    • Ungulates often asymptomatic
    • Can be detected in air up to 2 weeks post-partum and in soil for 6 months
  • Released by an infected animal during childbirth, though windborne spread can carry it at least 10 km
    • Placenta has an extremely high burden of bacteria
    • Can also be found in stool, urine, and milk
    • Unpasteurized milk
  • Inhaled by humans with an incubation period of 20 days (1 to 39 days)
    • Dose-dependent incubation period
    • Chronic Q fever can be up to 6 months
  • Worldwide distribution, except New Zealand
    • Hepatitis more in Europe, pneumonia more in US

Risk Factors

  • Working with or near animals, especially peripartum
  • Lab exposure
  • Unpasteurized milk

Pathophysiology

  • Bacteria enter lungs, where they proliferate in the macrophages and invade the bloodstream
    • Lives in the phagolysosome
    • Can cause graulomas
  • Alternatively, can enter via tick bite or via ingestion
  • Invasion of bloodstream causes systemic symptoms, with severity depending on the dose inhaled
  • QPH1 is a more virulent strain

Clinical Manifestations

  • Can present as asymptomatic, self-limited febrile illness lasting 2 to 14 days (most common), pneumonia, or hepatitis
    • Asymptomatic more common in pregnant women and children
  • Infective endocarditis, osteomyelitis, CNS infection including aseptic meningitis
  • Q fever in immunocompromised host, Q fever in infancy, Q fever in pregnancy
  • Post-Q fever fatigue syndrome

Acute Q fever

  • Fever is uniform finding in all syndromes
  • Chills, headache (severe), fatigue, and myalgias that lasts 2-21 days (14)
  • Can present with rash including urticaria
  • Palpable purpura can be seen in chronic Q fever (that is, endocarditis)

Pneumonia

  • Can present as an atypical pneumonia, a rapidly-progressing pneumonia, and an incidental pneumonia in a febrile patient (most common)
  • A community-acquired pneumonia that doesn't respond to first-line antibiotics (like Legionella and pneumonic tularemia)
  • Cough, though often not present, can be non-productive, productive, or bloody
  • More common in Americas than Europe

Hepatitis

  • Three forms:
    • An infectious hepatitis–like picture
    • Fever of unknown origin, with characteristic granulomas ("donut-like") on liver biopsy
    • An incidental finding in a patient with acute Q fever pneumonia
  • More common in Europe and Americas

CNS Infections

  • Can cause Miller-Fischer variant of Guillain-BarrΓ© syndrome

Endocarditis

  • Subacute or chronic febrile illess
  • Clubbing and hepatosplenomegaly are common
  • Higher titres are more convincing β‰₯1:6400

Diagnosis

  • Not readily culturable (nor should you try), though you can see it with Giemsa stain
  • PCR is possible though not common
  • Causes a false-positive RF, APLA
  • Main method of detection is serology

Serology

  • Immunofluorescence assay is standard; no need for EIA
  • Two phases of IgG antibodies (phase I and II)
    • Phase II corresponds more to acute
      • Positive if IgM >50 and IgG >200, or if there's a 4x rise in either titres
      • Detectable by 2 weeks, should be positive by 4
      • Peak at 2 months, then decrease except the IgG in cases of endocarditis
      • Also IgA, but not clinically relevant
    • Phase I corresponds more to chronic
      • Can test for IgG (useful) and IgA (useless) titres
      • IgG β‰₯ 800 consistent with chronic infection, and is one of the minor Duke criteria for endocarditis
      • IgG β‰₯ 6400 is suggestive of endovascular infection or endocarditis (major criteria),
  • Two ways to diagnose acute infection
    • Retrospectively with a fourfold rise in both titres from acute to chronic stage, or
    • One-time phase II IgM >50 and IgG >2000
  • Chronic infection is diagnosed clinically, with a phase I IgG titre greater than the phase II IgG titre, and both are at least IgG titre >1:1600
  • IgM antibodies are usually undetectable by 4 months, though IgG may persist for more than a decade

Management

  • Acute Q fever
    • Consider screening for bicuspid valve with TTE if high risk, or baseline TTE
    • Doxycycline 100mg po bid x 10-14 days
    • Second-line is fluoroquinolones or macrolides
    • Consider monitoring titres for some period afterwards
    • In patients with prosthetic heart valves, consider prolonged treatment as per chronic Q fever (like 1 year)
  • Chronic Q fever

Pregnancy

  • Coxiella loves the placenta
  • It can be a cause of flu-like illness in pregnant women with a potential exposure history
    • This can be associated with first-trimester pregnancy loss
  • Doxycycline and fluoroquinolones are contraindicated
  • TMP-SMX 1600/320 daily, make sure they're on folic acid supplementation
    • Continue it for the duration of pregnancy
    • Theoretic risk of hyperbilirubinemia in third trimester, so may consider holding it towards the end unless there's documented chronic infection
  • High risk of developing chronic infection, so titres should be monitored for at least 2 years
    • If persistent IgG > 800, consider TEE

Prevention

  • Vaccinate high-risk workers
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