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Q Fever

by William A. Petri, Jr., MD, PhD

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 PCR. Treatment is with doxycycline or chloramphenicol.

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 sp.

Q fever can be acute or chronic. Acute disease causes a febrile illness that often affects the respiratory system, although sometimes the liver is involved. Chronic Q fever 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

Cases occur among workers whose occupations bring them in close contact with farm animals or their products. Transmission is usually by inhalation of infected aerosols, but 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. Very rarely, the disease is transmitted from person to person.

Symptoms and Signs

The incubation period averages 18 to 21 days (range 9 to 28 days). Some infections are minimally symptomatic; however, most patients have influenza-like symptoms. Onset is abrupt, with fever, severe headache, chills, severe malaise, myalgia, anorexia, and sweats. Fever may rise to 40° C and persist 1 to > 3 wk. 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 elderly 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. Chronic Q fever hepatitis may manifest as FUO. Liver biopsy may show granulomas, which should be differentiated from other causes of liver granulomas (eg, TB, sarcoidosis, histoplasmosis, brucellosis, tularemia, syphilis).

Endocarditis resembles viridans group subacute bacterial endocarditis (see Infective Endocarditis); the aortic valve is most commonly affected, but vegetations may occur on any valve. Marked finger clubbing, arterial emboli, hepatomegaly, splenomegaly, and a purpuric rash may occur.

The mortality rate is only 1% of untreated patients but is higher in those with endocarditis. Some patients with neurologic involvement have residual impairment.

Diagnosis

  • Immunofluorescence assay or PCR of infected tissue

  • Sometimes acute and convalescent serologic tests

Symptoms do not readily suggest the diagnosis. 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 pneumonias. Contact with animals or animal products is an important clue.

Immunofluorescence assay (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. PCR can identify the organism in biopsy specimens. 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, CBC may be normal, but about 30% of patients have an elevated WBC count. Alkaline phosphatase, AST, and 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.

Treatment

  • Doxycycline

Primary treatment is doxycycline 200 mg po once followed by 100 mg po bid until the patient improves, has been afebrile for about 5 days, and has received treatment for at least 7 days. Chloramphenicol 500 mg po or IV qid for 7 days is 2nd-line treatment. Fluoroquinolones and macrolides are also effective.

For endocarditis, treatment needs to be prolonged (months to years to lifelong). Clinical signs, ESR, blood count, and antibody titers should be monitored to determine when to stop treatment. A tetracycline plus rifampin or ciprofloxacin is usually preferred. Some experts use hydroxychloroquine as an additional drug. When antibiotic treatment is only partially effective, damaged valves must be replaced surgically, although some cures have occurred without surgery. Clear-cut regimens for chronic hepatitis have not been determined.

Prevention

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). These vaccines are not available commercially in the US but may be obtained from special laboratories (eg, the US Army Medical Research Institute of Infectious Diseases in Fort Detrick, Maryland). 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.

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • PERIOSTAT, VIBRAMYCIN
  • No US brand name
  • ACHROMYCIN V
  • RIFADIN, RIMACTANE
  • PLAQUENIL
  • CILOXAN, CIPRO

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