Q-Fever - Coxiella burnetii

Diagnosis

Indications for Testing

Laboratory Testing

  • CDC laboratory confirmation of C. burnetii
  • Nonspecific testing – acute disease
    • CBC – 25% have thrombocytopenia
    • Serum transaminases – moderately elevated in many patients
    • Patients with endocarditis
      • Sedimentation rate, C-reactive protein – elevated
      • CBC – anemia, thrombocytopenia
      • Urinalysis – hematuria
  • Antibody titers by IFA, ELISA
    • Acute disease
      • Phases I and II – IgM increased
      • Phase II, IgG increased
      • May take 2-4 weeks after onset of symptoms to rise
      • May be detected up to 12 weeks after illness onset
    • Chronic disease
      • Phase I – IgG persistently increased
      • Endocarditis – IgG titer ≥1:800 is diagnostic 
  • PCR – helpful in patients where disease is suspected and titers are low
  • Immunohistochemical staining – not widely available
  • Culture tests – not recommended
    • Lack sensitivity
    • Available only in research laboratories

Imaging Studies

  • Echocardiogram

Monitoring

  • IgG phase I – monitor treatment efficacy; expect decreased IgG in successful therapy
  • May want to consider repeat serum testing using IgG phase I in patients with known valvular abnormalities, if initial testing was negative
  • Follow-up testing recommended for all patients with acute disease
    • Antibody titers
    • Echocardiogram

Clinical Background

Q-fever, a worldwide zoonosis, is caused by Coxiella burnetii and is named for a 1985 disease outbreak in Queensland, Australia.

Epidemiology

  • Incidence – <50/year in U.S.
  • Age – highest prevalence in 30s-60s
  • Sex – M>F
    • Women and children more commonly asymptomatic
  • Transmission
    • Important reservoirs of C. burnetii include cattle, sheep, and goats, as well as the rodents, cats, and birds that feed on them
    • Infection in these animals is enzootic and usually asymptomatic
    • Bacteria infects humans via
      • Inhaling contaminated dust particles and aerosols
      • Handling/ingesting infected raw meat or milk

Organism

  • Gram-negative coccobacillus
  • Obligate intracellular bacterial pathogen (family Coxiellaceae; order Legionellales) with worldwide distribution
  • Classified as a class B bioterrorism agent

Risk Factors

  • Occupational – farmers, veterinarians, abattoir workers, military personnel
  • Ingestion of unpasteurized dairy products
  • Underlying valve disease – risk factor for endocarditis

Pathophysiology

  • C. burnetii exists in two antigenic phases (phases I and II) – antigenic difference is important to diagnosis
    • Antibodies to both phase I and II antigens may persist for months or years after initial infection
  • Acute disease
    • Antibody levels to phase II antigens are usually higher (often by several orders of magnitude) than those for phase I antigens and are usually detected during the second week of symptoms
  • Chronic disease
    • Subsequent testing shows high antibody levels to phase I antigens and constant or decreasing levels of antibodies to phase II antigens
      • Because antibodies to phase I antigens generally require longer to appear, consistent high levels may indicate continued exposure to the bacteria
    • Signs and symptoms of inflammatory disease

Clinical Presentation

  • Incubation period – ~2-6 weeks
  • Acute disease symptoms
    • Most cases are self-limiting, flu-like illnesses
      • Fever peaks in 2-4 days near 40°C, then gradually declines over period of 1-2 weeks
    • Constitutional – malaise, anorexia, myalgias, weakness, intense headache
    • Pneumonia or bronchitis – tachypnea, rales, rhonchi, cough, wheezing
    • Hepatitis – nausea, vomiting, diarrhea, anorexia, elevated transaminases, rarely jaundice
    • Myocarditis, pericarditis
    • During pregnancy – abortion, prematurity, low birth weight
  • Chronic disease symptoms – rare (<1%)
    • Presence of endocarditis – pathognomonic for chronic disease
      • Occurs in patients with pre-existing heart valve damage (usually aortic and mitral valves), immunosuppression, or chronic renal disease
      • May result in culture-negative endocarditis
      • Symptoms – low-grade fever, cardiac failure, hepatosplenomegaly, clubbing of digits
    • Other organs may be involved – hepatitis, vascular infection, osteomyelitis, lymphadenitis

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Order to differentiate bacterial from viral etiology

   
Aspartate Aminotransferase, Serum or Plasma 0020007
Method: Quantitative Enzymatic

Order to rule out associated hepatitis

   
Coxiella burnetii (Q-Fever) Antibodies, IgG & IgM by IFA with Reflex to Titer 2003102
Method: Immunofluorescence Assay
(Indirect Fluorescent Antibody)

Confirm infectious agent as C. burnetii (Q-fever) in symptomatic patients

If C. burnetii IgG and/or IgM antibodies are detected, titer will be added

   
Coxiella burnetii (Q-Fever) Antibody IgG, Phase I & II by IFA 0050462
Method: Semi-Quantitative Indirect Fluorescent Antibody

Confirm infectious agent as C. burnetii (Q-fever) in symptomatic patients

Recommend testing of acute and convalescent sera

Initial testing may not be helpful; treatment should be based on clinical and other laboratory assessment

 
Coxiella burnetii (Q-Fever) Antibody IgG, Phase I by IFA 0050463
Method: Semi-Quantitative Indirect Fluorescent Antibody

Monitor treatment success via titers

Order to confirm chronic disease (eg, endocarditis)

  Follow up titers to confirm effectiveness of therapy in chronic disease
Sedimentation Rate, Westergren (ESR) 0040325
Method: Visual Identification

Use for patients with suspected chronic Q-fever

   
C-Reactive Protein 0050180
Method: Quantitative Immunoturbidimetry

Use in clinical scenarios associated with inflammation (autoimmune disease, connective tissue disease, rheumatoid arthritis, or sepsis)

Do not order for CVD risk assessment; use CRP high sensitivity

   
Urinalysis, Complete 0020350
Method: Reflectance Spectrophotometry/Microscopy

Determine presence of hematuria in suspected glomerulonephritis

   
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Antimicrobial Susceptibility - Bactericidal Assay 0060204
Method: Broth Microdilution
Coxiella burnetii (Q-Fever) Antibody IgG, Phase II by IFA 0050464
Method: Semi-Quantitative Indirect Fluorescent Antibody