Coxiella burnetii - Q-Fever

Q-fever is a worldwide zoonosis caused by Coxiella burnetii and named for a 1985 disease outbreak in Queensland, Australia. For definitive diagnosis in the early stages of illness it is recommended to use serologic tests in combination with PCR of whole blood or serum. Treatment should be initiated as soon as Q fever is suspected and should never be withheld pending the receipt of diagnostic test results.

Tabs Content

Clinical Overview

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

ARUP Lab Tests

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Coxiella burnetii (Q-Fever) Antibodies, IgG and IgM, Phase I and II with Reflex to Titer 2012634
Method: Semi-Quantitative Indirect Fluorescent Antibody

Recommended Use

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

Reflex pattern – for IgG or IgM testing, if any phase I or phase II screening result is indeterminate or positive, then titer(s) will be added

Coxiella burnetii (Q-Fever) Antibody IgG, Phase I and II with Reflex to Titer 2012625
Method: Semi-Quantitative Indirect Fluorescent Antibody

Recommended Use

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

Recommend testing of acute and convalescent sera

Reflex pattern – if either C. Burnetii antibody IgG phase I and/or phase II result is indeterminate or positive, then titer(s) will be added

Medical Experts

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

Slev, Patricia R., PhD, Laboratory Section Chief, Immunology, at ARUP Laboratories; Associate Professor of Clinical Pathology, University of Utah

References

Guidelines

Choosing Wisely. An initiative of the ABIM Foundation. [Accessed: Oct 2018]

General References

Cutler SJ, Bouzid M, Cutler RR. Q fever. J Infect. 2007; 54(4): 313-8. PubMed

Gikas A, Kokkini S, Tsioutis C. Q fever: clinical manifestations and treatment. Expert Rev Anti Infect Ther. 2010; 8(5): 529-39. PubMed

Hartzell JD, Wood-Morris RN, Martinez LJ, Trotta RF. Q fever: epidemiology, diagnosis, and treatment. Mayo Clin Proc. 2008; 83(5): 574-9. PubMed

Parker NR, Barralet JH, Bell AM. Q fever. Lancet. 2006; 367(9511): 679-88. PubMed

Terheggen U, Leggat PA. Clinical manifestations of Q fever in adults and children. Travel Med Infect Dis. 2007; 5(3): 159-64. PubMed

Tissot-Dupont H, Raoult D. Q fever. Infect Dis Clin North Am. 2008; 22(3): 505-14, ix. PubMed

Last Update: July 2018