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Coxiella burnetii - Q Fever

Last Literature Review: December 2024 Last Update:

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Brian R. Jackson, MD, MS
Brian R. Jackson, MD, MS
Adjunct Professor of Pathology and Biomedical Informatics, University of Utah
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Coxiella burnetii, the causative agent for Q fever, is primarily transmitted to humans via inhalation of particles excreted by livestock such as cattle, sheep, and goats; other forms of transmission (eg, human to human) are rare. ,  Infections may be either acute or chronic.  Acute infection is often mild or asymptomatic; however, pregnant individuals who are infected are at risk of miscarriage, stillbirth, and other adverse outcomes. ,  Chronic Q fever is rare. It often causes endocarditis, which is usually fatal if left untreated.  There are distinct antibody responses to two different antigenic phases (phase I and phase II) of C. burnetii infection. ,  The response to phase II antigens is higher in acute infection, and the response to phase I antigens is higher in chronic infection.  Laboratory testing for Q fever includes testing for antibody response to both phase I and phase II antigens. , 

Quick Answers for Clinicians

Is the initiation of treatment for Q fever dependent on laboratory confirmation of infection?

Because diagnostic serology tests will return negative results for the first 15 days of illness, treatment should begin before laboratory confirmation of Coxiella burnetii infection (Q fever). ,  Treatment should be initiated based on clinical suspicion, which may be informed by a combination of symptoms, patient history (including recent animal exposure), and evidence from nonspecific laboratory tests. , 

How are nonspecific laboratory tests used in the diagnosis of Q fever?

Certain standard blood tests, such as CBC and liver function tests, can support a diagnosis of Q fever (and assist in the decision to begin treatment) before confirmatory laboratory tests have been completed.  The combination of a low platelet count, a normal leukocyte count, and elevated liver enzymes is suggestive of acute Coxiella burnetii infection. 

Which individuals are at risk for developing chronic Q fever?

Less than 5% of individuals who contract acute Q fever develop a chronic infection, which may occur a few months to decades after the initial infection.  Individuals with acute Q fever should undergo a clinical assessment to determine the risk of developing chronic Q fever.  Those with valvular heart disease, arterial aneurysms, and vascular grafts are at high risk, as are individuals who are immunocompromised or who were infected while pregnant. 

Indications for Testing

Testing for acute Q fever (ie, C. burnetii infection) should be considered in individuals with flu-like symptoms (such as fever, headache, and chills) and occupational or travel-related exposure to potentially infected livestock. , , 

Testing for chronic Q fever may be considered for individuals with culture-negative endocarditis, particularly those with a compromised immune system or experiencing other early symptoms such as fatigue and fever. , 

Laboratory Testing

Serology is the most common diagnostic approach for C. burnetii infection, regardless of whether acute or chronic infection is suspected. For more information, refer to the CDC's case definition for Q fever. 

Acute Infection

Serology

The standard test for diagnosing acute C. burnetii infection is indirect fluorescent antibody (IFA) testing on paired acute and convalescent sera.  A fourfold increase in phase II immunoglobulin G (IgG) concentration is considered diagnostic for Q fever. , 

Because IgM antibodies may persist for months and are less specific than IgG antibodies, IgM titers should only be assessed in conjunction with IgG titers. 

Nucleic Acid Detection

Polymerase chain reaction (PCR) testing on serum or whole blood can be used to detect C. burnetii within the first week of illness before antibodies develop,  and PCR in combination with serology is recommended in the early stages of infection for a definitive diagnosis of acute Q fever.  However, a negative PCR result does not rule out infection and should not delay treatment. 

Blood Culture

Blood culture is not recommended for the detection of C. burnetii because the turnaround time is long and the test is difficult and only performed at specialized labs, such as the CDC. 

Chronic Infection

Chronic Q fever can be diagnosed when an individual exhibits both:

  • Elevated phase I IgG antibody titers 
  • A persistent focus of infection, such as endocarditis 

PCR testing may be performed on tissue, whole blood, or serum specimens. Particularly if endocarditis is present, serum antibody testing should be performed due to the limited sensitivity of whole blood PCR testing. ,  PCR or immunohistochemistry (IHC) testing of tissue specimens from the active site of infection may be useful. , 

References