Q Fever

Q fever is a zoonotic infection caused by Coxiella burnetii, an obligate intracellular, highly environmentally resistant bacterium.

Transmission is predominantly by inhalation of contaminated aerosols or dust from the birth products, urine, faeces or milk of infected livestock, particularly sheep, goats and cattle. The organism survives for extended periods in the environment because of its spore like resistant form, so transmission risk exists even without direct animal contact.

It presents either as an acute self limiting febrile illness or, in a small proportion of patients, as chronic infection. Chronic infection most seriously manifests as culture negative endocarditis, which carries substantial morbidity if not recognised and appropriately treated.

Pathophysiology and risk factors

• The organism exists in two antigenic phases. Phase two predominates in acute infection and phase one in chronic infection.
• Serological testing exploits this distinction, because the antibody response pattern differs between the two presentations.
• Occupational exposure to livestock (farmers, veterinarians, abattoir workers) is the principal risk factor. Infection can also follow more incidental exposure, because contaminated aerosols persist in the environment and disperse widely.
• Pre-existing valvular heart disease, vascular graft material, pregnancy and significant immunosuppression are important risk factors for progression to chronic infection after acute exposure.

• Acute Q fever is frequently asymptomatic or mild.
• Symptomatic disease presents as a non specific febrile illness with headache (often severe) and myalgia. In a substantial proportion there is atypical pneumonia or hepatitis, with deranged liver function tests and occasionally granulomatous hepatitis on biopsy where performed.
• In the majority of cases it resolves over one to two weeks even without specific treatment.
• Chronic Q fever develops months to years after the initial infection, which may have been asymptomatic and unrecognised at the time.
• It most commonly presents as endocarditis, characteristically affecting previously damaged or prosthetic heart valves. The presentation is insidious.
• Standard blood cultures stay persistently negative because the organism is fastidious and obligate intracellular. It is a leading cause of culture negative endocarditis, and diagnosis requires specific serological testing.
• Chronic infection can also affect vascular grafts or aneurysms, causing vascular infection with risk of aneurysm rupture.
• In pregnancy, chronic infection is associated with adverse outcomes including miscarriage and preterm delivery. Consider testing in pregnant women with a relevant occupational or environmental exposure history.
• Actively seek a history of exposure to livestock or their birth products in any patient with a compatible acute febrile illness, and particularly in the assessment of culture negative endocarditis.
• A meaningful proportion of confirmed cases do not recall a specific exposure, because transmission can be indirect and aerosol based.

• Serological testing (indirect immunofluorescence assay) is the primary diagnostic method. The pattern of phase one versus phase two antibody titres distinguishes acute from chronic infection.
• Acute infection is characterised by predominant phase two antibody elevation. Chronic infection is characterised by markedly elevated phase one antibody titres.
• An IgG phase one titre of 1 in 800 or greater is generally considered supportive of chronic infection in the appropriate clinical context.
• Polymerase chain reaction testing on blood gives additional confirmation. It is particularly useful in the early acute phase, before a reliable antibody response has developed.
• Polymerase chain reaction on tissue, such as valve tissue obtained at surgery where performed, confirms chronic infection.
• Echocardiography is essential in any patient with confirmed or suspected chronic Q fever. Keep a low threshold for transoesophageal imaging, because vegetations are frequently subtle with this organism.
• In investigating culture negative endocarditis, include Coxiella burnetii serology routinely in the standard diagnostic panel.
• Cardiac assessment (echocardiography) is generally recommended even in patients diagnosed with acute Q fever alone. It identifies pre-existing valvular abnormality, which indicates an elevated risk of progression to chronic infection and endocarditis.
• The result informs the duration and intensity of serological follow up.

• Mild acute Q fever is generally self limiting, so treatment is generally reserved for more significant symptomatic illness. It is also given to higher risk patients, including those with valvular heart disease, vascular graft material, or pregnancy.
• Where treatment is indicated, give doxycycline 100 mg orally twice daily for fourteen days. Earlier initiation is associated with more rapid symptomatic resolution.
• Chronic Q fever, most commonly presenting as endocarditis, requires prolonged combination antibiotic therapy. It is typically doxycycline 100 mg twice daily combined with hydroxychloroquine 200 mg three times daily.
• Continue treatment for a minimum of eighteen months for native valve infection and at least twenty four months for prosthetic valve infection. Chronic, intracellular infection is substantially more difficult to eradicate than acute disease.
• Hydroxychloroquine is included because it alkalinises the intracellular phagolysosomal environment where the organism resides. This enhances the bactericidal activity of doxycycline against this intracellular pathogen.
• Monitor phase one antibody titres by serology over the treatment course and beyond. They guide treatment duration and response.
• A satisfactory declining titre trend supports eventual treatment discontinuation. Optimal duration and the serological targets for stopping remain guided by specialist infectious disease input, given the complexity of this assessment.
• Consider surgical valve replacement for significant valvular destruction, heart failure, or failure of medical therapy to achieve adequate control. The indications follow similar principles to other forms of infective endocarditis.
• Continue the prolonged antibiotic regimen regardless of whether surgery is also required.
• Pregnant women with acute Q fever diagnosed during pregnancy need specific management guidance, given the recognised association with adverse pregnancy outcomes.
• Co trimoxazole is generally used as an alternative to doxycycline throughout pregnancy, because tetracyclines are contraindicated. Continue it until delivery, then follow up serologically to assess for evolution to chronic infection.
• For those in relevant occupational risk groups, prevention includes appropriate personal protective equipment when handling livestock birth products.
• Vaccination is an additional preventive measure where accessible. It is available in specific countries for defined high risk occupational groups and is not widely available in most jurisdictions.