Query (Q) fever is a zoonotic illness caused by Coxiella burnetii. It is transmitted by inhalation or ingestion. The disease may be acquired by the respiratory or digestive route. The clinical features are nonspecific, and therefore Q fever serologic testing should be done if a patient has undiagnosed persistent fever without positive blood cultures.

A peculiarity of Coxiella burnetii, the causative agent of Q fever, is its phase variation, due to differences in the lipopolysaccharide levels. When first isolated the agent expresses one set of antigens called phase I antigens which are so shaped as to prevent antibodies from gaining access to proteins on the bacterial surface.

This results in persistence of the organisms in the body even after the acute infection subsides, shown by seropositivity throughout the patient’s life. However, subcultured C. burnetii expresses phase II antigens which renders it susceptible to antibody attack. This difference is taken advantage of to distinguish between acute and chronic Q fever.

Image Credit: CDC

Diagnosis of Q Fever

The symptoms and signs of acute Q fever are extremely variable and the most valuable clue is the worker’s exposure to infected meat. Symptoms occur in less than half of infected individuals, and are mostly very mild. They include three major presentations: a flu-like illness, pneumonia (often atypical) and hepatitis. Other features may include myocarditis or pericarditis, skin rashes, renal involvement, various forms of anemia, and meningitis, all uncommon.

Chronic infection with Q fever is diagnosed when the infection lasts more than 6 months from the initial phase, and complicates the course of illness in about 5% of patients. It is caused by bacterial proliferation within macrophages and high antibody titers in blood. The heart is usually affected, but also arteries or bones, or the liver. Risk factors for endocarditis in chronic Q fever include a history of valve disease or immunocompromised. Other features are rare but may include conditions such as aneurysm infections, osteoarthritis, and pericardial effusion or interstitial fibrosis of the lungs.

Acute Q Fever Diagnosis

The diagnosis is made on the basis of the history of potential exposure, with specific immunologic tests relying on the detection of antibodies using immunofluorescence assay. These are very specific and sensitive. Phase II IgM antibody titers of 50 or more, and IgG 200 or more, confirms acute Q fever, and is positive between 2-4 weeks of infection, peaking by 2 months, and falling slowly thereafter. Phase I IgG titers of 800 or more indicate chronic infection.

A more sensitive test is the use of the polymerase chain reaction, which is especially important because of the potential for early detection of the bacterium, but is now used only in reference and research laboratories.

Histologic examination of biopsy tissue stained with Giemsa staining may show doughnut granulomas or fibrin rings, which are typical but not specific. Isolation and culture is not practiced outside laboratories with level 3 biosafety norms because a single bacterium can infect a new case in phase I.

Q Fever Endocarditis

This condition is diagnosed by meeting clinical criteria for endocarditis along with serologic evidence or isolation of C. burnetii. A single phase I IgG antibody titer of 800 or more is included in the modified Duke criteria, but if titers are low or absent, as may happen with concomitant immunosuppression, a PCR is invaluable in early diagnosis.