Clinical and Laboratory Diagnosis for Q Fever

The reference standard test for the serologic diagnosis of acute Q fever is the indirect fluorescent antibody (IFA) test using C. burnetii antigen, performed on paired serum samples to demonstrate a significant (fourfold or more) rise in antibody titers.

The first sample should be taken as early in the disease as possible, preferably in the first week of symptoms, and the second sample should be taken 3 to 6 weeks later.

In most Q fever cases, the first IgG IFA titer is typically low, or "negative," and the second typically shows a fourfold or greater increase in IgG antibody levels. A negative test during the first week of illness does not rule out Q fever as a cause of illness.

There are two distinct antigenic phases (phase I and phase II) to which humans develop antibody responses. In acute infection, an antibody response to C. burnetii phase II antigen is predominant and is higher than antibody levels to phase I antigen; the reverse is true in chronic infection which is associated with a rising phase I IgG titer that may be higher than phase II IgG.

IgM antibodies usually rise at the same time as IgG, near the end of the first week of illness, and remain elevated for months or longer and therefore provide limited diagnostic value on their own. IgM antibodies are less specific than IgG antibodies and more likely to result in a false positive. For these reasons, physicians requesting IgM serologic titers should also request concurrent IgG titers.

Antibodies to C. burnetii may remain elevated for months or longer after the disease has resolved. Approximately 3% of healthy people in the U.S. adult population and up to 20% of people in high-risk professions (e.g., veterinarians, ranchers, etc.) have elevated antibody titers from past infection with C. burnetii.

If only one sample is tested, it can be difficult to interpret the findings. Paired samples taken 3 to 6 weeks apart demonstrating fourfold or greater rise in antibody titer provides the best evidence for a correct diagnosis of acute Q fever.

During the acute phase of illness, a sample of whole blood (or serum at some laboratories) can be tested by polymerase chain reaction (PCR) assay to determine if a patient has Q fever. This method is most sensitive in the first week of illness before the appearance of C. burnetii-specific antibodies. It rapidly decreases in sensitivity following the administration of doxycycline.

Although a positive PCR result is helpful, a negative result does not rule out the diagnosis. Treatment should not be withheld due to a negative result.

Culture isolation of C. burnetii is not recommended for routine diagnosis because it is difficult, time consuming, and is only available at specialized laboratories. Routine hospital blood cultures cannot detect the organism.

Diagnosis of chronic Q fever

Chronic Q fever is confirmed by elevated phase I IgG antibody ≥1:1024 and an identifiable persistent focus of infection (e.g., endocarditis). Whole blood, serum or tissue biopsies may be tested by PCR for C. burnetii. PCR of whole blood has low sensitivity in patients with chronic Q fever endocarditis, so serum antibody titers should also be tested.

PCR or immunohistochemistry of biopsy specimens from the site of active infection has also been used to diagnose chronic Q fever. These tests may be appropriate for endocarditis patients undergoing valve replacement surgery or patients with hepatitis.

For more in-depth information about the diagnosis of Q fever, please see the diagnostic section in the MMWR Diagnosis and Management of Q fever—United States, 2013.

For information on submitting a sample to CDC for testing, please see Information for Public Health Officials.

Information such as recent travel to rural or agricultural communities where infected livestock may be present, or employment in high-risk occupations, such as veterinarians and farmers, can be helpful in making a diagnosis.

Chronic Q fever is a risk for anyone with a history of acute Q fever. It is more frequent in persons with valvular disease, blood vessel abnormalities, immunosuppressed persons, and with women who are pregnant when they become infected. Persons with these risk factors should be routinely monitored using serologic methods for the 2 years following diagnosis of acute Q fever to ensure rapid diagnosis and treatment.

Healthcare providers should also look at routine blood tests, such as a complete blood cell count or a chemistry panel. A prolonged fever with low platelet count, normal leukocyte count, and elevated liver enzymes are suggestive of acute Q fever infection but may not be present in all patients.

After a suspect diagnosis is made based on clinical suspicion and treatment has begun, specialized laboratory testing should be used to confirm the diagnosis of Q fever.