Q-fever is a worldwide zoonosis caused by Coxiella burnetii and named for a 1985 disease outbreak in Queensland, Australia. For definitive diagnosis in the early stages of illness it is recommended to use serologic tests in combination with PCR of whole blood or serum. Treatment should be initiated as soon as Q fever is suspected and should never be withheld pending the receipt of diagnostic test results.
Diagnosis
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, 2016; American Society for Clinical Pathology)
- Usually elevated
- If CRP not available, order erythrocyte sedimentation rate (ESR)
- CBC – anemia, thrombocytopenia
- Urinalysis – hematuria
- C-reactive protein (CRP)
- Antibody titers by immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA) – acute disease
- Perform IgG and IgM, phase I and II, antibody testing
- Results
- Phases I and II – IgM increased
- Phase II – IgG increased
- Titers may not increase for 2-4 weeks after onset of symptoms
- May be detected up to 12 weeks after illness onset
- Chronic disease
- Phase I – IgG persistently increased
- Endocarditis – IgG titer ≥1:800 is diagnostic
- Polymerase chain reaction (PCR) – helpful in patients with suspected disease and low titers
- Can be performed on tissue fluids (eg, cerebrospinal fluid [CSF], pleural)
- Most sensitive in first week of illness
- Sensitivity rapidly diminishes with antibiotic therapy
- Immunohistochemical staining – not widely available
- Culture – not recommended
- Lack sensitivity
- Available only in research laboratories due to extreme infectivity
Imaging Studies
Echocardiogram
Monitoring
- IgG phase I – monitor treatment efficacy; successful therapy should result in decreased IgG
- 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
Background
Epidemiology
- Incidence – <50/year in U.S.
- Age – highest prevalence in 30s-60s
- Sex – M>F
- Women and children more commonly asymptomatic
- Transmission
- Main 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
- Inhalation of contaminated dust particles and aerosols
- Handling/ingestion of 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 – farming, veterinary medicine, abattoir work, military work
- Underlying valve disease – risk factor for endocarditis
- Ingestion of unpasteurized dairy products
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 second week of symptoms
- Chronic disease
- Subsequent testing shows high levels of antibodies to phase I antigens and constant or decreasing levels of antibodies to phase II antigens
- Because antibodies to phase I antigens generally require more time to appear, consistently high levels may indicate continued exposure to the bacteria
- Signs and symptoms of inflammatory disease
- Subsequent testing shows high levels of antibodies to phase I antigens and constant or decreasing levels of antibodies to phase II antigens
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 preexisting 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 affected, resulting in hepatitis, vascular infection, osteomyelitis, lymphadenitis
ARUP Laboratory Tests
Confirm infectious agent as C. burnetii (Q-fever) in symptomatic patients
Semi-Quantitative Indirect Fluorescent Antibody
Confirm infectious agent as C. burnetii (Q-fever) in symptomatic patients
Recommend testing of acute and convalescent sera
Semi-Quantitative Indirect Fluorescent Antibody
Reflex pattern: if either C. Burnetii antibody IgG phase I and/or phase II result is indeterminate or positive, then titer(s) will be added
Order to differentiate bacterial from viral etiology
Automated Cell Count/Differential
Order to rule out associated hepatitis
Quantitative Enzymatic
Preferred test to detect acute phase inflammation (eg, autoimmune diseases, connective tissue disease, rheumatoid arthritis, infection, or sepsis)
Quantitative Immunoturbidimetry
Screen for various metabolic and kidney disorders
Reflectance Spectrophotometry/Microscopy
Nonspecific test used to detect inflammation associated with infections, cancers, and autoimmune diseases
Visual Identification
Medical Experts
Couturier

Slev

References
Choosing Wisely
Choosing Wisely. An initiative of the ABIM Foundation. [Accessed: Dec 2020]
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Miller HK, Binder AM, Peterson A, et al. Trends in Q fever serologic testing by immunofluorescence from four large reference laboratories in the United States, 2012-2016. Sci Rep. 2018;8(1):16670.
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