Coxiella burnetii - Q Fever

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 women who are infected are at risk of miscarriage, stillbirth, and other adverse outcomes.  Chronic Q fever is rare, but 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.  For more information, see the Diagnosis and Management of Q Fever recommendations from the CDC. 

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 7-15 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 based on a combination of symptoms, patient history (including recent animal exposure), and evidence from nonspecific laboratory tests. 

Which nonspecific laboratory tests are useful in assessing for 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?

Fewer 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 in 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, see the CDC 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 immunoglobulin M (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 lead to treatment being delayed. 

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:

  • Phase I IgG antibody level of ≥1:1,024 (generally higher than the level of phase II antibodies)
  • A persistent focus of infection, such as endocarditis 

PCR testing on whole blood is not an appropriate diagnostic test for chronic Q fever due to its lack of sensitivity.  PCR or immunohistochemistry (IHC) testing of tissue specimens from the active site of infection may be useful. 

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Medical Experts

Contributor

Jackson

Brian R. Jackson, MD, MS
Associate Professor of Pathology (Clinical); Adjunct Associate Professor, Biomedical Informatics, University of Utah
Medical Director, Support Services, IT, and Business Development, ARUP Laboratories

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