Q-Fever - Coxiella burnetii

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 – 25% have thrombocytopenia
- Serum transaminases – moderately elevated in many patients
- Patients with endocarditis
  - Sedimentation rate, C-reactive protein – elevated
  - CBC – anemia, thrombocytopenia
  - Urinalysis – hematuria
Antibody titers by IFA, ELISA
- Acute disease
  - Phases I and II – IgM increased
  - Phase II, IgG increased
  - May take 2-4 weeks after onset of symptoms to rise
  - May be detected up to 12 weeks after illness onset
- Chronic disease
  - Phase I – IgG persistently increased
  - Endocarditis – IgG titer ≥1:800 is diagnostic
PCR – helpful in patients where disease is suspected and titers are low
Immunohistochemical staining – not widely available
Culture tests – not recommended
- Lack sensitivity
- Available only in research laboratories

Imaging Studies

Echocardiogram

Monitoring

IgG phase I – monitor treatment efficacy; expect decreased IgG in successful therapy
May want to 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

Q-fever, a worldwide zoonosis, is caused by Coxiella burnetii and is named for a 1985 disease outbreak in Queensland, Australia.

Epidemiology

Incidence – <50/year in U.S.
Age – highest prevalence in 30s-60s
Sex – M>F
- Women and children more commonly asymptomatic
Transmission
- Important 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
  - Inhaling contaminated dust particles and aerosols
  - Handling/ingesting 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 – farmers, veterinarians, abattoir workers, military personnel
Ingestion of unpasteurized dairy products
Underlying valve disease – risk factor for endocarditis

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 the second week of symptoms
Chronic disease
- Subsequent testing shows high antibody levels to phase I antigens and constant or decreasing levels of antibodies to phase II antigens
  - Because antibodies to phase I antigens generally require longer to appear, consistent 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%)
- Presence of endocarditis – pathognomonic for chronic disease
  - Occurs in patients with pre-existing 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 involved – hepatitis, vascular infection, osteomyelitis, lymphadenitis

Tests

Tests generally appear in the order most useful for common clinical situations

Test name: CBC with Platelet Count and Automated Differential

ARUP #: 0040003

Methodology: Automated Cell Count/Differential

Use:

Order to differentiate bacterial from viral etiology

Test name: Aspartate Aminotransferase, Serum or Plasma

ARUP #: 0020007

Methodology: Quantitative Enzymatic

Use:

Order to rule out associated hepatitis

Test name: Coxiella burnetii (Q-Fever) Antibodies, IgG & IgM by IFA with Reflex to Titer

ARUP #: 2003102

Methodology: Immunofluorescence Assay
(Indirect Fluorescent Antibody)

Use:

Confirm infectious agent as C. burnetii (Q-fever) in symptomatic patients

If C. burnetii IgG and/or IgM antibodies are detected, titer will be added

Test name: Coxiella burnetii (Q-Fever) Antibody IgG, Phase I & II by IFA

ARUP #: 0050462

Methodology: Semi-Quantitative Indirect Fluorescent Antibody

Use:

Confirm infectious agent as C. burnetii (Q-fever) in symptomatic patients

Recommend testing of acute and convalescent sera

Limitations:

Initial testing may not be helpful; treatment should be based on clinical and other laboratory assessment

Test name: Coxiella burnetii (Q-Fever) Antibody IgG, Phase I by IFA

ARUP #: 0050463

Methodology: Semi-Quantitative Indirect Fluorescent Antibody

Use:

Monitor treatment success via titers

Order to confirm chronic disease (eg, endocarditis)

Follow-up: Follow up titers to confirm effectiveness of therapy in chronic disease

Test name: Sedimentation Rate, Westergren (ESR)

ARUP #: 0040325

Methodology: Visual Identification

Use:

Use for patients with suspected chronic Q-fever

Test name: C-Reactive Protein

ARUP #: 0050180

Methodology: Quantitative Immunoturbidimetry

Use:

Use in clinical scenarios associated with inflammation (autoimmune disease, connective tissue disease, rheumatoid arthritis, or sepsis)

Do not order for CVD risk assessment; use CRP high sensitivity

Test name: Urinalysis, Complete

ARUP #: 0020350

Methodology: Reflectance Spectrophotometry/Microscopy

Use:

Determine presence of hematuria in suspected glomerulonephritis

Additional Tests Available

Test name: Antimicrobial Susceptibility - Bactericidal Assay

ARUP #: 0060204

Methodology: Broth Microdilution

Comments:

Test name: Coxiella burnetii (Q-Fever) Antibody IgG, Phase II by IFA

ARUP #: 0050464

Methodology: Semi-Quantitative Indirect Fluorescent Antibody

Comments:

References

General

Medical Reviewers

Couturier, Marc Roger, PhD, D(ABMM). Medical Director Microbial Immunology, and Assistant Medical Director Parasitology/Fecal Testing and Infectious Disease Rapid Testing at ARUP Laboratories; Assistant Professor of Pathology, University of Utah

Comprehensive Review: July 2012
Last Update: March 2013