Coxiella burnetii - Q-Fever

Indications for Testing

Flu-like illness with appropriate risk factors
Presence of blood culture-negative endocarditis

Laboratory Testing

CDC laboratory confirmation of C. burnetii
Nonspecific testing – acute disease
- CBC – thrombocytopenia common
- Serum transaminases – moderately elevated in many patients
- Patients with endocarditis
  - C-reactive protein (CRP)
    - Preferred test to detect inflammatory processes (Choosing Wisely: 5 Things Physicians and Patients Should Question, 2015; American Society for Clinical Pathology)
    - Usually elevated
    - If CRP not available, order erythrocyte sedimentation rate (ESR)
  - CBC – anemia, thrombocytopenia
  - Urinalysis – hematuria
Antibody titers by IFA, ELISA
- Acute disease
  - Perform phase I and II IgG and IgM antibody testing
  - Results
    - Phases I and II – IgM increased
    - Phase II, IgG increased
    - May take 2-4 weeks after onset of symptoms for increased titers
    - 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
- Can be performed on tissue fluids (eg, CSF, pleural)
- Most sensitive in first week of illness
- Sensitivity rapidly diminishes with antibiotic therapy
Immunohistochemical staining – not widely available
Culture tests – not recommended
- Lack sensitivity
- Available only in research laboratories due to extreme infectivity

Imaging Studies

Echocardiogram

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

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%)
- Defined as infection lasting >6 months
- 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

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.

Coxiella burnetii (Q-Fever) Antibodies, IgG and IgM, Phase I and II with Reflex to Titer 2012634
Method: Semi-Quantitative Indirect Fluorescent Antibody

Recommended Use

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

Reflex pattern – for IgG or IgM testing, if any phase I or phase II screening result is indeterminate or positive, then titer(s) will be added

Coxiella burnetii (Q-Fever) Antibody IgG, Phase I and II with Reflex to Titer 2012625
Method: Semi-Quantitative Indirect Fluorescent Antibody

Recommended Use

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

Recommend testing of acute and convalescent sera

Reflex pattern – if either C. Burnetii abs IgG phase I and/or phase II result is indeterminate or positive, then titer(s) will be added

Limitations

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

Guidelines

American Society for Clinical Pathology. Choosing Wisely - Five Things Physicians and Patients Should Question. An initiative of the ABIM Foundation. [Last revision Feb 2015; Accessed: Jan 2016]