Q Fever: Diagnosis & Laboratory Guidance for Clinicians

Laboratory Findings

Because the signs and symptoms of Q fever are not specific to this disease, it is difficult to make an accurate diagnosis without appropriate laboratory testing. Whenever possible, specimens for lab testing of acutely ill patients should be obtained prior to starting antimicrobial therapy.
C. burnetii may be detected in infected tissues by using immunohistochemical staining and DNA detection methods, or by direct isolation of the agent via culture.
A diagnosis of Q fever may also be confirmed with serologic testing to detect the presence of antibodies to C. burnetii antigens.
The indirect immunofluorescence assay (IFA) is the most dependable and widely used serologic method. ELISA tests are also becoming more widely available.
Testing of paired (acute and convalescent) serum specimens, taken 2-3 weeks apart, is preferred, because changes in antibody titers provide the best evidence of recent infection. In some cases, a single high serum antibody titer may be considered evidence of probable infection.
Serologic tests evaluate antibodies to two distinct antigenic forms of C. burnetii called phase I and phase II.
In acute cases of Q fever, the antibody level to phase II is usually higher than that to phase I, often by several orders of magnitude, and antibodies are generally detectable as early as the second week of illness.
Phase I antibodies to C. burnetii appear after development of Phase II antibodies. Both Phase I and Phase II antibodies may remain elevated for long periods of time in the absence of chronic infection. In chronic Q fever, phase I antibody titers are much greater than phase II titers. Titers ≥ 1:800 are considered diagnostic in endocarditis patients for chronic Q fever.
It has been recommended that acutely ill patients be followed by serology for two years after illness to determine if chronic disease develops.
Both phase I and phase II antibodies have been known to persist for months or years after initial infection.
Recent studies have shown that greater accuracy in the diagnosis of Q fever can be achieved by looking at specific levels of classes of antibodies other than IgG, namely IgA and IgM. Combined detection of IgM and IgA in addition to IgG improves the specificity of the assays and provides better accuracy in diagnosis.

Other Test Methods

Early diagnosis of acute Coxiella burnetii infection is possible using PCR assays. Blood samples collected in EDTA anticoagulant blood tubes should be obtained prior to antibiotic therapy.
Cultures (isolation) can be done, but many laboratories will not have the appropriate facilities (must be approved for biosafety and Select Agents).
Chronic Q fever can be confirmed in heart valve tissue by culture, PCR assays, or immunohistochemistry. These assays are not widely available, so you may need to contact your state health department to arrange for testing.

General Information for Specimen Collection and Submission

The American Society for Microbiology is currently working on development and dissemination of sentinel laboratory information. Sentinel procedures can now be accessed at http://www.asm.org/Policy/index.asp?bid=667. Protocols for sentinel laboratories (e.g. hospital labs, etc) are no longer posted on the CDC Website.
Information for reference laboratories will continue to be available on the Laboratory Response Network (LRN) secure Website (for questions: e-mail lrn@cdc.gov; toll free HelpDesk 1-866-LRN-LABS [1-866-576-5227].
If exposure to C. burnetii is suspected, cannot be ruled out, and/or a bioterrorist event is suspected, follow facility policies, immediately notify the clinical laboratory and the state public health laboratory director.

The state public health laboratory director will coordinate testing as necessary, including rapid testing or confirmation of lab test results.
The state public health laboratory/state public health department will notify local FBI agents as appropriate.
The FBI and state public health laboratory/state public health department will coordinate the transfer of isolates/specimens to an LRN laboratory that can perform rapid and confirmatory tests for C. burnetii.

Preserve original specimens pursuant to a potential criminal investigation and possible transfer to an appropriate LRN laboratory.

Start chain-of-custody documentation.
Follow guidelines from healthcare facility clinical laboratory and state public health laboratory about chain-of-custody issues, packaging and shipping.

Whenever possible, obtain patient specimen(s) prior to initiation of antimicrobial therapy.
If Coxiella burnetii is identified in a specimen, all storage, transfer, and handling of the specimen will fall under the Select Agent regulations. The CDC Select Agent Home page