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Q Fever

By

William A. Petri, Jr

, MD, PhD, University of Virginia School of Medicine

Last full review/revision Mar 2022| Content last modified Sep 2022
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Q fever is an acute or chronic disease caused by the rickettsial-like bacillus Coxiella burnetii. Acute disease causes sudden onset of fever, headache, malaise, and interstitial pneumonitis. Chronic disease manifestations reflect the organ system affected. Diagnosis is confirmed by several serologic techniques, isolation of the organism, or polymerase chain reaction (PCR). Treatment is with doxycycline.

Coxiella burnetii is a small, intracellular, pleomorphic bacillus that is no longer classified as Rickettsia. Molecular studies have reclassified it as Proteobacteria in the same group as Legionella Legionella Infections Legionella pneumophila is a gram-negative bacillus that most often causes pneumonia with extrapulmonary features. Diagnosis requires specific growth media, serologic or urine antigen... read more <i >Legionella</i> Infections species.

Q fever can be

  • Acute

  • Chronic

Acute disease causes a febrile illness that often affects the respiratory system, although sometimes the liver is involved. Women infected during pregnancy have an increased risk of spontaneous abortion and preterm delivery.

Chronic Q fever occurs in < 5% of patients. It usually manifests as endocarditis or hepatitis; osteomyelitis may occur.

Worldwide in its distribution, Q fever is maintained as an inapparent infection in domestic or farm animals. Sheep, cattle, and goats are the principal reservoirs for human infection. C. burnetii persists in stool, urine, milk, and tissues (especially the placenta), so that fomites and infective aerosols form easily. C. burnetii is also maintained in nature through an animal-tick cycle, but arthropods are not involved in human infection.

Etiology of Q Fever

Cases of Q fever occur among workers whose occupations bring them in close contact with farm animals (which are often asymptomatic) or their products. Transmission is usually by inhalation of infectious aerosols that can travel long distances affecting people living downwind of an infected goat or sheep farm. The disease can also be contracted by ingesting infective raw milk.

C. burnetii is very virulent, resists inactivation, and remains viable in dust and stool for months; even a single organism can cause infection. Because of these characteristics, C. burnetii is a potential biological warfare agent Biological Agents as Weapons Biological warfare (BW) is the use of microbiological agents for hostile purposes. Such use is contrary to international law and has rarely taken place during formal warfare in modern history... read more .

Very rarely, the disease is transmitted from person to person.

Symptoms and Signs of Q Fever

The incubation period averages 18 to 21 days (range 9 to 28 days). Acute Q fever is often asymptomatic; in other patients, it begins abruptly with influenza-like symptoms: fever, severe headache, chills, severe malaise, myalgia, anorexia, and sweats. Fever may rise to 40° C and persist 1 to > 3 weeks.

Rarely, acute Q fever manifests as encephalitis or meningoencephalitis.

Respiratory symptoms (a dry nonproductive cough, pleuritic chest pain) appear 4 to 5 days after onset of illness. These symptoms may be particularly severe in older or debilitated patients. During examination, lung crackles are commonly noted, and findings suggesting consolidation may be present. Unlike rickettsial diseases, acute Q fever does not cause a rash.

Acute hepatic involvement, occurring in some patients, resembles viral hepatitis, with fever, malaise, hepatomegaly with right upper abdominal pain, and possibly jaundice. Headache and respiratory signs are frequently absent.

A post-Q fever fatigue syndrome has been reported to occur in up to 20% of patients with acute Q fever (1 Symptoms and signs references Q fever is an acute or chronic disease caused by the rickettsial-like bacillus Coxiella burnetii. Acute disease causes sudden onset of fever, headache, malaise, and interstitial pneumonitis... read more ). Patients report severe fatigue, muscle pains, headache, photophobia, and/or mood and sleep changes.

Chronic Q fever may manifest within a few weeks to many years after the initial infection. People with a history of cardiac valvular defects, arterial aneurysms, or vascular grafts are at increased risk of developing chronic Q fever. Pregnancy and immunosuppression have also been linked to the development of chronic Q fever. Hepatitis may manifest as fever of unknown origin Fever of Unknown Origin (FUO) Fever of unknown origin (FUO) is body temperature ≥ 38.3° C (≥ 101° F) rectally that does not result from transient and self-limited illness, rapidly fatal illness, or disorders with clear-cut... read more . Liver biopsy may show granulomas, which should be differentiated from other causes of liver granulomas (eg, tuberculosis, sarcoidosis, histoplasmosis, brucellosis, tularemia, syphilis).

Endocarditis resembles culture-negative subacute bacterial endocarditis Infective Endocarditis Infective endocarditis is infection of the endocardium, usually with bacteria (commonly, streptococci or staphylococci) or fungi. It may cause fever, heart murmurs, petechiae, anemia, embolic... read more Infective Endocarditis ; the aortic valve is most commonly affected, but vegetations may occur on any cardiac valve. Marked finger clubbing, arterial emboli, hepatomegaly, splenomegaly, and a purpuric rash may occur. Only 20 to 40 % of patients who develop Q fever endocarditis have symptoms of acute infection.

The case-fatality rate of acute Q fever is only about 1% in untreated patients. Untreated chronic Q fever endocarditis is always fatal. Adequate antibiotic treatment reduces the mortality rate for Q fever endocarditis to <5% (2 Symptoms and signs references Q fever is an acute or chronic disease caused by the rickettsial-like bacillus Coxiella burnetii. Acute disease causes sudden onset of fever, headache, malaise, and interstitial pneumonitis... read more ). Some patients with neurologic involvement have residual impairment.

Symptoms and signs references

Diagnosis of Q Fever

  • Immunofluorescence assay (IFA) or polymerase chain reaction (PCR) of infected tissue

  • Sometimes acute and convalescent serologic tests

Symptoms do not readily suggest the diagnosis of Q fever. Early on, Q fever resembles many infections (eg, influenza, other viral infections, salmonellosis, malaria, hepatitis, brucellosis). Later, it resembles many forms of bacterial, viral, and mycoplasmal and other atypical pneumonias. Contact with animals or animal products is an important clue.

IFA of infected tissue is the diagnostic method of choice; alternatively, enzyme-linked immunosorbent assay (ELISA) may be done. Acute and convalescent serum specimens (typically complement fixation) may be used. Antibodies to phase II antigen are used to diagnose acute disease, and antibodies to both phase I and phase II antigens are used to diagnose chronic disease.

PCR can identify the organism in biopsy specimens, but negative results do not rule out the diagnosis.

C. burnetii may be isolated from clinical specimens, but only by special research laboratories; routine blood and sputum cultures are negative.

Patients with respiratory symptoms or signs require chest x-ray; findings may include atelectasis, pleural-based opacities, pleural effusion, and lobar consolidation. The gross appearance of the lungs may resemble bacterial pneumonia but, histologically, more closely resembles psittacosis and some viral pneumonias.

In acute Q fever, complete blood count may be normal, but about 30% of patients have an elevated white blood cell count. Alkaline phosphatase, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels are mildly elevated to 2 to 3 times the normal level in typical cases. If obtained, liver biopsy specimens often show diffuse granulomatous changes.

Diagnosis of Q fever endocarditis can be difficult because blood cultures are negative and vegetative cardiac valve lesions are small and are visualized by echocardiography in only about 12% of patients (see CDC: Diagnosis and Management of Q Fever — United States, 2013: Recommendations from CDC and the Q Fever Working Group).

Treatment of Q Fever

  • Doxycycline

For acute Q fever, primary treatment is doxycycline 200 mg orally once followed by 100 mg orally twice a day in adults until the patient improves, has been afebrile for about 5 days, and has received treatment for at least 7 days; typically, 2 to 3 weeks of treatment is required. Tetracycline resistance has not been documented.

Although some tetracyclines can cause tooth staining in children < 8 years of age, the Centers for Disease Control and Prevention (CDC) advises that a course of doxycycline 2.2 mg/kg orally or IV twice a day is warranted (1 Treatment references Q fever is an acute or chronic disease caused by the rickettsial-like bacillus Coxiella burnetii. Acute disease causes sudden onset of fever, headache, malaise, and interstitial pneumonitis... read more ), given for 5 days for mild illness and for 10 days for high-risk children. Research indicates that short courses of doxycycline (5 to 10 days, as used for rickettsial disease) can be used in children without causing tooth staining or weakening of tooth enamel (2 Treatment references Q fever is an acute or chronic disease caused by the rickettsial-like bacillus Coxiella burnetii. Acute disease causes sudden onset of fever, headache, malaise, and interstitial pneumonitis... read more ). Pregnant women may be given trimethoprim/sulfamethoxazole, 160 mg/800 mg twice a day throughout pregnancy, but not beyond 32 weeks gestation.

For endocarditis, treatment needs to be prolonged (months to years to lifelong), typically for at least 18 months (3 Treatment references Q fever is an acute or chronic disease caused by the rickettsial-like bacillus Coxiella burnetii. Acute disease causes sudden onset of fever, headache, malaise, and interstitial pneumonitis... read more ). Doxycycline 100 mg orally twice a day in adults plus hydroxychloroquine 200 mg orally every 8 hours is currently recommended. Owing to the cardiac adverse effects of hydroxychloroquine, patients on this drug should have their QTc interval monitored with repeated ECGs. Clinical signs, erythrocyte sedimentation rate, blood count, and antibody titers should be monitored to help determine when to stop treatment. Consultation with an infectious disease specialist may help with managing the complexities of the disease and its treatment. Frequently, antibiotic treatment is only partially effective, and damaged valves must be replaced surgically, although some cures have occurred without surgery.

For chronic granulomatous hepatitis, the optimal regimen has not been determined.

Treatment references

Prevention of Q Fever

Vaccines are effective, and in Australia, where a Q fever vaccine is commercially available, vaccination is recommended to protect people with occupational risk (eg, slaughterhouse and dairy workers, rendering-plant workers, herders, woolsorters, farmers).

Prevaccination screening with skin and blood tests should be done to identify preexisting immunity to Q fever because vaccinating people who already have immunity can cause severe local reactions.

Key Points

  • Sheep, cattle, and goats are the principal reservoirs for human Q fever infection, which occurs worldwide.

  • Transmission to humans is usually by inhalation of infectious aerosols; arthropods are not involved.

  • Acute symptoms resemble influenza; respiratory symptoms may be particularly severe in older or debilitated patients.

  • Chronic Q fever occurs in < 5% of patients and usually manifests as endocarditis or hepatitis.

  • Diagnose using immunofluorescence assay or PCR testing of infected tissue.

  • Treat acute Q fever with doxycycline, typically for 2 to 3 weeks; endocarditis requires prolonged treatment (months to years to lifelong).

  • A vaccine to prevent Q fever is commercially available but only in Australia.

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