Q Fever (Coxiella burnetii Infection)

Essentials of Diagnosis

• Exposure to sheep, goats, cattle; some laboratory-acquired infections

• Acute or chronic febrile illness: headache, cough, prostration, and abdominal pain

• Pneumonitis, hepatitis, or encephalopathy; less often, vascular infections or chronic fatigue syndrome

• A common cause of culture-negative endocarditis

General Considerations

• Q fever, a reportable and significantly underestimated disease in the United States, is caused by the gram-negative intracellular coccobacillus Coxiella burnetii

• Human infection occurs via inhalation of aerosolized bacteria (in dust or droplets) from feces, urine, milk, or products of conception of infected animals

• Ingestion and skin penetration are other recognized routes of transmission

• There is a known occupational risk for animal handlers, slaughterhouse workers, veterinarians, laboratory workers, and other workers exposed to animal products

• In the United States, over 60% of cases do not report an exposure to potentially infectious animals; drinking raw milk may be an infectious exposure

• Human-to-human transmission does not seem to occur, but maternal-fetal infection can occur

• Infection post-liver transplant has been reported

• Chronic Q fever is now termed "persistent focalized infections"

• Asymptomatic infection is common

• For the remaining cases, a febrile illness develops after an incubation period of 2–3 weeks, usually accompanied by headache, relative bradycardia, prostration, and muscle pains

• Clinical course may be acute, chronic (duration 6 months or longer), or relapsing

• Pneumonia and granulomatous hepatitis are the predominant manifestations in the acute form

• Less common manifestations include

  • Skin rashes (maculopapular or purpuric)

  • Fever of unknown origin

  • Myocarditis

  • Pericarditis

  • Aortic aneurysms

  • Aseptic meningitis

  • Encephalitis

  • Orchitis

  • Iliopsoas abscess

  • Spondylodiscitis

  • Tenosynovitis

  • Granulomatous osteomyelitis (more often seen in children)

  • Regional (mediastinal)

  • Diffuse lymphadenopathies

• Culture-negative endocarditis is most common presentation in patients with persistent focalized infections

  • Risk factors include

    • Immunocompromised state

    • Preexisting valvular conditions

    • Male sex

    • Age above 40 years

    • Valvular prosthesis (mechanical or bioprosthesis)

  • Clinical manifestations of endocarditis are nonspecific with fever, night sweats, and weight loss

  • Sudden cardiac insufficiency, stroke, or other embolic and mycotic aneurysms can develop

  • Rarely, urticaria, edema, erythema nodosum, and arthralgias are reported

• New infection or reactivation of Q fever can occur in pregnant women and is associated with

  • Spontaneous abortions

  • Intrauterine growth retardation

  • Intrauterine fetal death

  • Premature delivery

  • Oligohydramnios (when infection occurs during first trimester)

Differential Diagnosis

• Viral, mycoplasmal, and bacterial pneumonias

• Viral hepatitis

• Brucellosis

• Legionnaire disease

• Murine or scrub typhus

• Kawasaki disease

• Tuberculosis

• Psittacosis

Laboratory Findings

• Elevated liver biochemical tests

• Leukocytosis

• A fourfold rise between acute and convalescent sera by indirect immunofluorescence is diagnostic of the infection

• Real-time PCR for C burnetii DNA is helpful only in early stage of infection

• Diagnostic tests using Immuno-PCR and combining PCR with ELISA improve the sensitivity and specificity during the first 2 weeks after the onset of symptoms

• An automated epifluorescence assay has > 95% sensitivity for the detection of phase I antigens in persistent infection

  • Phase variation is the change that occurs in the outer lipopolysaccharide membrane of the Coxiella burnetii with chronicity of infection

  • Acute infection usually has higher phase II antibodies than phase I antibodies

• C burnetii-specific interferon-gamma, interferon-gamma/IL-2 ratio has a sensitivity of 79% and a specificity and 97% for the diagnosis of persistent infection

Imaging

• Radiographs of the chest can show patchy pulmonary infiltrates

• Echocardiography should be done in all patients with acute Q fever to screen for underlying valvular disease

• Initial imaging and follow-up with serial 18-FDG PET/CT scan may be helpful in identifying chronic infection and monitoring treatment response

• For acute infection, doxycycline (100 mg orally twice daily) for 14 days or at least 3 full days after defervescence is recommended

• For native valve endocarditis and prosthetic valve endocarditis, most experts recommend a combination oral therapy with doxycycline (100 mg twice a day) plus quinolone or rifampin or hydroxychloroquine for approximately 18 months and 24 months, respectively

• For patients with endocarditis, clinical cure is possible without valve replacement

• All infected pregnant women should be given long-term trimethoprim-sulfamethoxazole (320/1600 mg orally for the duration of pregnancy but not beyond 32 weeks' gestation)

Complications

• Patients with persistent focalized infections may have higher risk for lymphadenitis and progression to diffuse B-cell lymphoma and follicular lymphoma

Follow-Up

• Patients should be monitored for at least 5 years due to risk of relapse

Prevention

• Prevention is based on detection of the infection in livestock, reduction of contact with infected and parturient animals or contaminated dust; special care when working with animal tissues; and effective pasteurization of milk

• A whole-cell Q fever vaccine is available in Australia for persons with high-risk exposures, although there are reports of vaccine failure more than 15 days after vaccination

• C burnetii is a category B bioterrorism agent; in the setting of a bioterrorist attack,

  • Postexposure prophylaxis with doxycycline 100 mg orally twice a day for 5–7 days should be started 8–12 days after exposure

  • Pregnant women may take trimethoprim-sulfamethoxazole as an alternative

Prognosis

• Mortality rate is usually low (even in untreated patients), except when endocarditis develops