Coxiella burnetii - Q-Fever

Diagnosis

Indications for Testing

• Flu-like illness with appropriate risk factors
• Presence of blood culture-negative endocarditis

Laboratory Testing

• CDC laboratory confirmation of C. burnetii
• Nonspecific testing – acute disease
  • CBC – thrombocytopenia common
  • Serum transaminases – moderately elevated in many patients
  • Patients with endocarditis
    • C-reactive protein (CRP)
      • Preferred test to detect inflammatory processes (Choosing Wisely, 2016; American Society for Clinical Pathology)
      • Usually elevated
      • If CRP not available, order erythrocyte sedimentation rate (ESR)
    • CBC – anemia, thrombocytopenia
    • Urinalysis – hematuria
• Antibody titers by immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA) – acute disease
  • Perform IgG and IgM, phase I and II, antibody testing
  • Results
    • Phases I and II – IgM increased
    • Phase II – IgG increased
    • Titers may not increase for 2-4 weeks after onset of symptoms
    • May be detected up to 12 weeks after illness onset
• Chronic disease
  • Phase I – IgG persistently increased
  • Endocarditis – IgG titer ≥1:800 is diagnostic
• Polymerase chain reaction (PCR) – helpful in patients with suspected disease and low titers
  • Can be performed on tissue fluids (eg, cerebrospinal fluid [CSF], pleural)
  • Most sensitive in first week of illness
  • Sensitivity rapidly diminishes with antibiotic therapy
• Immunohistochemical staining – not widely available
• Culture – not recommended
  • Lack sensitivity
  • Available only in research laboratories due to extreme infectivity

Imaging Studies

Echocardiogram

Monitoring

• IgG phase I – monitor treatment efficacy; successful therapy should result in decreased IgG
• Consider repeat serum testing using IgG phase I in patients with known valvular abnormalities, if initial testing was negative
• Follow-up testing recommended for all patients with acute disease
  • Antibody titers
  • Echocardiogram

Background

Epidemiology

• Incidence – <50/year in U.S.
• Age – highest prevalence in 30s-60s
• Sex – M>F
  • Women and children more commonly asymptomatic
• Transmission
  • Main reservoirs of C. burnetii include cattle, sheep, and goats, as well as the rodents, cats, and birds that feed on them
  • Infection in these animals is enzootic and usually asymptomatic
  • Bacteria infects humans via
    • Inhalation of contaminated dust particles and aerosols
    • Handling/ingestion of infected raw meat or milk

Organism

• Gram-negative coccobacillus
• Obligate intracellular bacterial pathogen (family Coxiellaceae; order Legionellales) with worldwide distribution
• Classified as a class B bioterrorism agent

Risk Factors

• Occupational – farming, veterinary medicine, abattoir work, military work
• Underlying valve disease – risk factor for endocarditis
• Ingestion of unpasteurized dairy products

Pathophysiology

• C. burnetii exists in two antigenic phases (phases I and II) – antigenic difference is important to diagnosis
  • Antibodies to both phase I and II antigens may persist for months or years after initial infection
• Acute disease
  • Antibody levels to phase II antigens are usually higher (often by several orders of magnitude) than those for phase I antigens and are usually detected during second week of symptoms
• Chronic disease
  • Subsequent testing shows high levels of antibodies to phase I antigens and constant or decreasing levels of antibodies to phase II antigens
    • Because antibodies to phase I antigens generally require more time to appear, consistently high levels may indicate continued exposure to the bacteria
  • Signs and symptoms of inflammatory disease

Clinical Presentation

• Incubation period – ~2-6 weeks
• Acute disease symptoms
  • Most cases are self-limiting, flu-like illnesses – fever peaks in 2-4 days near 40°C, then gradually declines over period of 1-2 weeks
  • Constitutional – malaise, anorexia, myalgias, weakness, intense headache
  • Pneumonia or bronchitis – tachypnea, rales, rhonchi, cough, wheezing
  • Hepatitis – nausea, vomiting, diarrhea, anorexia, elevated transaminases, rarely jaundice
  • Myocarditis, pericarditis
  • During pregnancy – abortion, prematurity, low birth weight
• Chronic disease symptoms – rare (<1%)
  • Defined as infection lasting >6 months
  • Presence of endocarditis – pathognomonic for chronic disease
  • Occurs in patients with preexisting heart valve damage (usually aortic and mitral valves), immunosuppression, or chronic renal disease
  • May result in culture-negative endocarditis
  • Symptoms – low-grade fever, cardiac failure, hepatosplenomegaly, clubbing of digits
  • Other organs may be affected, resulting in hepatitis, vascular infection, osteomyelitis, lymphadenitis