Q fever is a zoonotic systemic febrile illness caused by Coxiella burnetii that may be acute or chronic. The concept of persistent localized disease may soon replace that of chronic Q fever.

C. burnetii infection

• C. burnetii is found worldwide.
• Common animal reservoirs are cattle, sheep, and goats.
• Pets such as cats, rabbits, and pigeons are also reservoirs.
• A parturient cat caused an outbreak in Nova Scotia just by delivering in the same room as a card game.
• Most cases are found in individuals who have direct contact with infected animals (e.g., farmers, veterinarians) or who are exposed to contaminated animal urine, feces, milk, or placental tissues.
• Q fever is seen more often in men than in women (ratio of 3:1).
• Its incidence in the U.S. is increasing, with more than 30 cases recently reported in U.S. due to military personnel recently deployed to Iraq and Afghanistan.
• Travel to Middle Eastern and African countries poses the greatest risk.
• C. burnetii is a CDC class B bioterrorism agent.
• Q fever may be acquired from ingestion of unpasteurized milk or dairy products.

• Acute Q fever presentation:
  • 1. Fever
  • 2. Pneumonia (usually mild and atypical)
  • 3. Hepatitis
  • 4. Meningoencephalitis (rare)
  • 5. Many cases are asymptomatic
• Chronic/persistent localized Q fever presentation (duration of infection >6 mo):
  • 1. Chronic endocarditis
  • 2. Vascular infection (aneurysms and vascular prostheses)
  • 3.Bone and joint infections (culture-negative osteomyelitis or prosthetic joint infection)
• Most common clinical symptoms:
  • 1. Chills
  • 2. Sweats
  • 3. Nausea
  • 4. Vomiting
  • 5. Cough, nonproductive
  • 6. Headache (usually severe and persistent)
  • 7. Fatigue
• Most frequent physical findings:
  • 1. Fever
  • 2. Inspiratory rales
  • 3. Purpuric rash
  • 4. Hepatomegaly
  • 5. Splenomegaly
• Infected pregnant women may be asymptomatic acutely, yet fetal wastage may occur

• Q fever is caused by the Proteobacteria C. burnetii.
• C. burnetii is a gram-negative coccobacillus transmitted from arthropods to animals to human beings.
• The disease is acquired most often by inhalation of aerosols. In the lungs, it proliferates in macrophages and then gains access to the bloodstream, producing a transient bacteremia. Thereafter it can invade many organs, most commonly the lungs and liver (Fig. E1).
• There is an incubation period of 3 to 30 days before systemic symptoms manifest.
• Persons with abnormal heart valves, prosthetic valves, and endovascular grafts are at high risk of progression to chronic Q fever. This includes individuals with bicuspid aortic valves.

Q fever can have various presentations and must be in the differential diagnosis of fever, hepatitis, pneumonia, endocarditis, and meningitis. Situations that should prompt serologic testing for Q fever are described in Table E1.

• CBC, erythrocyte sedimentation rate (ESR), and liver function tests
• Urinalysis
• Serology
• Chest radiography

In acute Q fever:

• CBC and white blood cell count are usually normal.
• Thrombocytopenia can occur (25%).
• Elevation of hepatic transaminases (two to three times the normal range) may be seen.
• Antibody detection by immunofluorescence assay is the most commonly used method because of its high sensitivity and specificity. Complement fixation (CF) shows a fourfold rise in titer between acute and convalescent samples.
• Acute Q fever (phase II antigen and IgG ≥200 and IgM ≥50).
• Polymerase chain reaction is desirable in early disease.
• Testing has been approved by the FDA and can be obtained from the CDC through the state health department.

In chronic Q fever (almost always endocarditis):

• ESR is elevated.
• Anemia is present.
• Microscopic hematuria.
• Blood cultures are almost always negative.
• MIF (microimmunofluorescence) titer of >1:800 to phase I antigen is diagnostic.

• Chest radiographs may be abnormal, showing segmental lobe consolidation.
• Pleural effusions (35%).
• Transthoracic echocardiography after the diagnosis of acute Q fever can be used to stratify risk of progression to endocarditis.
• PET/CT imaging may be instrumental in determining the focus of persistent localized or chronic Q fever.

Oxygen as needed in patients with pneumonia

• Acute Q fever can be treated with doxycycline (100 mg bid) for 14 to 21 days or
• Clarithromycin is the macrolide of choice for acute infection given intolerance of doxycycline
• Ofloxacin 200 mg PO tid or ciprofloxacin 875 mg PO bid for 14 to 21 days
• Hydroxychloroquine plus doxycycline for endocarditis associated with Q fever
• Fluoroquinolones are recommended for suspected meningoencephalitis because of excellent penetration into the CNS
• Pregnant women may be treated with trimethoprim/sulfamethoxazole until the seventh month of gestation

• Chronic Q fever is treated with a combination of two antibiotics; doxycycline 100 mg bid and hydroxychloroquine 200 mg PO tid is the preferred therapy.
• Duration of treatment: 2 to 3 yr, at minimum 18 mo.
• Strongly consider prophylactic treatment for exposed individuals with preexistent high-risk cardiac lesions, pregnant women even if asymptomatic, and persons with persistently elevated anticardiolipin antibodies, lupus anticoagulant, antismooth muscle antibodies, or antimitochondrial antibodies.

• Patients with acute Q fever respond well to antibiotics, with deaths rarely reported.
• Up to 20% of patients develop a post-Q fever fatigue syndrome.

Mortality rate in chronic Q fever endocarditis is high (24%). Many patients will need valve replacement surgery.

Referral to an infectious disease expert is recommended in any cases of suspected acute or chronic Q fever.

Drug levels must be monitored and serial serologies evaluated.

Q fever has been a reportable disease in the U.S. since 1999. The CDC must be notified of cases.

• An acellular (CMR) vaccine is available in the U.S. However, vaccines that are available in other countries such as Australia have been more thoroughly studied.
• Infected patients do not require specific isolation precautions.
• Q fever derived its name in 1935 from Derrick, who was suspicious of a new disease during a series of acute febrile illnesses in abattoir workers of Queensland, Australia, justifying the name of Q fever (for “query”).