eMedicine Specialties > Infectious Diseases > Bacterial Infections

Q Fever: Differential Diagnoses & Workup

Author: Alexandre Lacasse, MD, MSc, Fellow in Infectious Diseases, University of Tennessee at Memphis
Coauthor(s): Kerry O Cleveland, MD, Associate Professor of Medicine, University of Tennessee College of Medicine; Consulting Staff, Department of Internal Medicine, Division of Infectious Diseases, Methodist Healthcare of Memphis; Hari Polenakovik, MD, Consultant Physician in Infectious Diseases and General Medicine, Department of Medicine, Western Health, Australia; Annie Ruest, MD, FRCPC, Consultant Physician in Infectious Diseases and Medical Microbiology, Departments of Medicine and Medical Biology, Laval University, Quebec City, Canada; Christian P Sinave, MD, Associate Professor, Department of Medical Microbiology and Infectious Diseases, University of Sherbrooke, Canada
Contributor Information and Disclosures

Updated: Nov 18, 2008

Differential Diagnoses

Abortion
Influenza
Acute interstitial pneumonitis
Lymphoma, Non-Hodgkin
Aseptic Meningitis
Meningitis
Chronic Fatigue Syndrome
Meningoencephalitis
Connective-tissue diseases
Myocarditis
Cytomegalovirus
Pericarditis, Acute
Drug-induced hepatitis
Pneumonia, Atypical Bacterial
Ebstein-Barr virus
Pneumonia, Viral
Ehrlichiosis
Rocky Mountain Spotted Fever
Fever of Unknown Origin
Sarcoidosis
Granulomatous hepatitis
Southern tick-associated rash illness (STARI)
Hepatitis, Viral
Spontaneous abortion
Hodgkin Disease
TORCH syndrome (toxoplasmosis, rubella, cytomegalovirus, and herpes simplex infections)
Infective Endocarditis
Visceral leishmaniasis

Other Problems to Be Considered

Placentitis
Vascular graft infections
Osteomyelitis

Workup

Laboratory Studies

Nonspecific studies

  • Acute Q fever
    • CBC count usually shows a normal WBC count, mild thrombocytopenia, and, in rare cases, hemolytic anemia.
    • Liver function tests usually show mild elevation of transaminases and alkaline phosphatase without hyperbilirubinemia.
    • Several positive autoimmune antibodies, including antismooth muscle and antiphospholipid, may be seen.
    • Cerebrospinal fluid examination may show a mononuclear pleocytosis with mildly increased protein concentration and normal glucose levels.
    • C burnetii can be seen on smears or frozen tissue prepared with a routine Giemsa stain.
    • Histopathologic changes consistent with doughnut granulomata are not specific for C burnetii.
  • Chronic Q fever
    • Elevated sedimentation rate
    • Elevated gamma globulins (polyclonal)
    • Rheumatoid factor
    • Anemia of chronic disease
    • Increased creatinine levels

Cultures

Q fever can be definitively diagnosed via culture isolation of C burnetii. This is technically difficult and can be performed in only laboratories equipped with biosafety level 3 containment.

Serology

Most cases of Q fever are diagnosed based on detection of phase I and II antibodies. The 3 serological techniques used for diagnosis include indirect immunofluorescence, complement fixation, and enzyme-linked immunosorbent assay (ELISA). Significant titers may take 2-4 weeks to appear. Laboratory values vary considerably, so clinicians must interpret results according to their local standards.

  • Indirect immunofluorescence is currently the preferred method.
    • Acute Q fever
      • Phase II IgM of 1:50 or more; usually undetectable after 4 months but can last 12 months or more
      • Phase II IgG of 1:200 or more
      • Phase II titers of 1:100 or less make the diagnosis of acute Q fever unlikely.
      • In a reference French laboratory, these values showed 100% specificity.
    • Chronic Q fever
      • Phase I IgG of 1:800 more is considered diagnostic of endocarditis (one of major modified Duke criteria).
      • Phase II IgM titers are lower or absent.
      • Phase II IgG titers are usually greater than 1:1600. They can last up to 12 years after an outbreak.
      • The main predictive criterion of clinical cure is detection of phase I IgG titer of less than 1:200.
  • Complement fixation is less sensitive and specific than indirect immunofluorescence. The time to positivity may take longer than IF. Different cutoff values are also used. IgG levels usually fall within 3 years.
  • ELISA is comparable to indirect immunofluorescence.
  • A 4-fold increase between acute and convalescent paired sera yields the highest specificity.
  • False-positive results may occur in legionellosis and leptospirosis.
  • Serologic follow-up to detect a rise in phase I IgG titers of 1:800 or more can be performed twice every 3 months. If detected, transesophageal echocardiography and serum real-time polymerase chain reaction (PCR) techniques can be performed in an attempt to diagnose endocarditis.3,7 Sensitivities may be as low as 18% in early disease.

Molecular techniques

In certain reference laboratories, PCR techniques can be used on resected cardiac valves with greater sensitivity than serum assays. C burnetii organisms can persist in tissues even after prolonged antimicrobial treatment.5 Although still controversial, serum PCR may be used to diagnose acute Q fever in the first 2 weeks of the disease. It should also be reserved for seronegative patients in the subsequent 2 weeks and not used later than 4 weeks following onset.7

Imaging Studies

  • Acute Q fever
    • Chest radiography frequently shows nonspecific segmental or lobar abnormalities. Multiple round opacities and pleural effusions may also be visible.
    • Echocardiography may show pericardial effusion with pericarditis.
  • Chronic Q fever
    • Chest radiography may reveal signs of interstitial fibrosis and pseudotumor.
    • Echocardiography may show vegetations, although less frequently than observed with other organisms. Rates as low as 12% have been reported. These vegetations tend to be smaller and located beneath endothelial surfaces.5

Other Tests

Acute Q fever: ECG may show T-wave abnormalities if myocarditis and pericarditis are present.

Histologic Findings

Classic doughnut granulomata may be observed in the liver and bone marrow. They consist of a fibrin ring surrounding an empty fat vacuole. These granulomata, although frequently associated with Q fever, are not specific. They can also occur in Hodgkin lymphoma, typhoid fever, cytomegalovirus infection, infectious mononucleosis, and allopurinol hypersensitivity.

More on Q Fever

Overview: Q Fever
Differential Diagnoses & Workup: Q Fever
Treatment & Medication: Q Fever
Follow-up: Q Fever
References
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References

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Further Reading

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Keywords

Q fever, query fever, Coxiella burnetii, C burnetii, Rickettsia burnetii, R burnetii, Rickettsia diaporica, R diaporica, zoonosis, zoonotic transmission, farm animals, livestock, bacterial infection, farm infection, chronic Q fever, chronic fatigue syndrome

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Contributor Information and Disclosures

Author

Alexandre Lacasse, MD, MSc, Fellow in Infectious Diseases, University of Tennessee at Memphis
Alexandre Lacasse, MD, MSc is a member of the following medical societies: American College of Physicians, American Medical Association, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Coauthor(s)

Kerry O Cleveland, MD, Associate Professor of Medicine, University of Tennessee College of Medicine; Consulting Staff, Department of Internal Medicine, Division of Infectious Diseases, Methodist Healthcare of Memphis
Kerry O Cleveland, MD is a member of the following medical societies: American College of Physicians, American Medical Association, Infectious Diseases Society of America, and Society for Healthcare Epidemiology of America
Disclosure: Nothing to disclose.

Hari Polenakovik, MD, Consultant Physician in Infectious Diseases and General Medicine, Department of Medicine, Western Health, Australia
Hari Polenakovik, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Annie Ruest, MD, FRCPC, Consultant Physician in Infectious Diseases and Medical Microbiology, Departments of Medicine and Medical Biology, Laval University, Quebec City, Canada
Annie Ruest, MD, FRCPC is a member of the following medical societies: Canadian Infectious Disease Society and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Christian P Sinave, MD, Associate Professor, Department of Medical Microbiology and Infectious Diseases, University of Sherbrooke, Canada
Christian P Sinave, MD is a member of the following medical societies: American Society for Microbiology and Canadian Infectious Disease Society
Disclosure: Nothing to disclose.

Medical Editor

John M Leedom, MD, Professor of Medicine, Keck School of Medicine, University of Southern California; Chief, Division of Infectious Diseases, Department of Internal Medicine, Los Angeles County, University of Southern California Medical Center
John M Leedom, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society for Microbiology, Infectious Diseases Society of America, International AIDS Society, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Joseph F John Jr, MD, FACP, FIDSA, FSHEA, Clinical Professor of Medicine, Molecular Genetics and Microbiology, Medical University of South Carolina; Associate Chief of Staff for Education, Ralph H Johnson Veterans Affairs Medical Center
Disclosure: BioMerieux Honoraria Review panel membership; Cubist Honoraria Review panel membership; Pfizer Honoraria Speaking and teaching; Merck Stock dividends stock holdings

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

 
 
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