Last reviewed: 23 Dec 2021
Last updated: 10 Dec 2020



History and exam

Key diagnostic factors

  • abrupt onset of high fever
  • flu-like illness
  • severe headache
  • cough
  • inspiratory crackles, rhonchi, or wheezing
  • hepatomegaly

Other diagnostic factors

  • exanthemas
  • pleuritic chest pain
  • seizures
  • coma
  • chronic fatigue
  • signs of endocarditis or vascular infection (persistent focalized infection)
  • other signs of persistent focalized infection
  • other signs of acute infection

Risk factors

  • exposure to infected animals
  • occupational exposure
  • travel or residency in endemic areas
  • male sex
  • age 30 to 70 years
  • immunosuppression
  • preexisting cardiac disease
  • preexisting vasculopathy
  • pregnancy

Diagnostic investigations

1st investigations to order

  • indirect immunofluorescence assay (IFA)
  • polymerase chain reaction (PCR)
  • CBC
  • CRP
  • LFTs
  • activated partial thromboplastin time (aPTT)
  • IgG anticardiolipin (aCL) antibodies

Investigations to consider

  • cerebrospinal fluid cell count and differential
  • cerebrospinal fluid protein
  • cerebrospinal fluid glucose
  • CXR
  • transthoracic echocardiography (TTE)
  • transesophageal echocardiography (TEE)
  • liver ultrasound
  • abdominal CT scan or ultrasound
  • chest CT
  • brain CT
  • 18F-fluorodeoxyglucose (FDG) PET/CT imaging
  • lymph node biopsy
  • immunohistochemistry
  • fluorescence in situ hybridization (FISH)

Treatment algorithm



Joshua Hartzell, MD, MS-HPEd, FACP, FIDSA

Division of Infectious Diseases

Uniformed Services University of the Health Sciences




JH declares he has no competing interests. The opinions or assertions contained herein are the private ones of the reviewer and are not to be construed as official or reflecting the views of the Department of Defense, the Uniformed Services University of the Health Sciences, or any other agency of the US Government.


Dr Joshua Hartzell would like to gratefully acknowledge Dr Matthieu Million, Professor Didier Raoult, and Dr Nilmarie Guzman, previous contributors to this topic.


MM and DR are authors of several references cited in this topic. NG declares that she has no competing interests.

Peer reviewers

Ron Behrens, MD, FRCP

Consultant in Tropical and Travel Medicine

Hospitals for Tropical Diseases

Senior Lecturer

London School of Hygiene and Tropical Medicine




RB has provided expert testimony on behalf of the Crown, to the courts in the UK, on Q fever.

Jennifer McQuiston, DVM, MS, DACVPM

Epidemiology Team

Rickettsial Zoonoses Branch

National Center for Zoonotic Vectorborne and Enteric Diseases

Centers for Disease Control and Prevention




JM declares that she has no competing interests.

Dimitrios Chatzidimitriou, MD, PhD

Clinical Microbiologist

National Influenza Center

Second Department of Microbiology

Aristotle University of Thessaloniki Medical School




DC declares that he has no competing interests.

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