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Pathology of Q fever (Coxiella Burnetii)

Dr Sampurna Roy MD




Q fever is caused by Coxiella burnetii, a bacteria, that is distributed globally. It was first described in Australia in 1937.

C. burnetii is a strict intracellular, Gram-negative bacterium. It is intracellular in macrophages.

Mode of Infection:

C. burnetii infects a wide range of animals, from arthropods to humans. The organism passes from the tick host to cattle, sheep, goat etc. Aerosol droplets spread the infection from person to person.

i) Most commonly, air borne by breathing air contaminated by drying animal placentas or other products of birth.

ii) By coming in contact with infected soil or wool.

ii) Less commonly, by ingestion of contaminated milk.

iii) Rarely by tick bite.

iv) It occurs in veterinarians, dairy workers, livestock farmers, laboratory workers and workers handling meat, skin, wool and fertilizer.

v) Rarely, Q fever has been spread through blood transfusion, from a pregnant woman to her fetus, or through sex.

Incubation period:  Normally 9-18 days.

Clinical features:

A. Asymptomatic- Seropositive cases. Classically, it is stated that approximately 60% of individuals are asymptomatic during C. burnetii primary infection.

Pregnancy may activate infection.

B. Acute Q fever: Isolated febrile syndrome or flu-like illness. Starts with influenza -like fever followed by myalgia, headache, sweating. It is usually self limited and rarely fatal. 

Symptoms can be mild or severe. People who develop severe disease may experience infection of the lungs (pneumonia) or liver (hepatitis).

Women who are infected during pregnancy may be at risk for miscarriage, stillbirth, pre-term delivery, or low infant birth weight.

C. Chronic Q fever:  Chronic Q fever may start 2-20 years after infection.

Chronic infective endocarditis with vegetation is the main complication of the chronic form of Q fever

Coxiella Burnetii endocarditis is very rare.

Rickettsiae are seen as extracellular colonies in the vegetations on the valve.  

Blood cultures are negative and diagnosis is essentially based on indirect immunofluorescence serum analysis.

It may be associated with involvement of liver.

Glomerulonephritis occurs in some patients with chronic Q fever endocarditis.


(i) Bronchopneumonia  with interstitial pneumonitis.

(ii) Exudate contains macrophage, lymphocytes, RBC & neutrophils.

(iii) Alveolar septa are thickened with mononuclear cell infiltrate.

(iv) Intracellular organisms in monocytes are present.

(v) Granulomas may be present in liver, spleen and bone marrow.

Granulomas contain central vacuolar space- "doughnut / ring granuloma".

Such granulomas are typical of Q fever, caused by the rickettsial bacterium Coxiella burnetii.

There is a central empty space that contains immunoglobulins reactive to Coxiella burnetii , epithelioid cells and a fibrin mesh between & outside epithelioid cells.

Doughnut granulomas are highly indicative of Coxiella infections; however, they are not specific to Coxiella infections and have been seen in Cytomegalovirus, Epstein-Barr virus, Brucella and Salmonella infections, leishmaniasis, Hodgkin and non-Hodgkin lymphomas, and immune disorders.

In Q fever granulomas are present in the liver: 

Differential diagnosis:  Granulomas are also seen in lymphoma, allopurinol drug effect, toxoplasmosis , Epstein-Barr Virus infection  and CMV infection, leishmaniasis, Hepatitis A and staphylococcal septicaemia.

In Q fever granulomas are present in the marrow: 

Differential diagnosis: Granulomas are also present in Tuberculosis, brucellosis , leishmaniasis , histoplasmosis , Hodgkin's disease , sarcoidosis .



Further reading:  

From Q Fever to Coxiella burnetii Infection: a Paradigm Change

Serology in chronic Q fever is still surrounded by question marks.

Survey of laboratory animal technicians in the United States for Coxiella burnetii antibodies and exploration of risk factors for exposure.

Multiple "doughnut" granulomas in Coxiella burnetii infection (Q fever).

A fatal case of chronic Q fever with cardiovascular involvement

Acute Q fever in Israel: clinical and laboratory study of 100 hospitalized patients.

Q fever: a rare cause of endocarditis.  

Abdominal aortic aneurysm and Coxiella burnetii infection: report of three cases and review of the literature.

Acute Q fever pneumonia: a review of 80 hospitalized patients.

Immunohistologic demonstration of Coxiella burnetii in the valves of patients with Q fever endocarditis.

Epidemiologic features and clinical presentation of acute Q fever in hospitalized patients: 323 French cases.




Dr Sampurna Roy  MD

Consultant  Histopathologist (Kolkata - India)

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