Criteria
Centers for Disease Control and Prevention (CDC): Q fever (Coxiella burnetii) 2009 case definition - acute[84]
Clinical criteria
Acute fever and one or more of the following: rigors, severe retrobulbar headache, acute hepatitis, pneumonia, or raised liver enzyme levels.
Laboratory criteria
Serological evidence of a fourfold change in Immunoglobulin G (IgG)-specific antibody titre to C burnetii phase 2 antigen by indirect immunofluorescence assay (IFA) between paired serum samples (one sample taken during the first week of illness and a second sample taken 3-6 weeks later, antibody titres to phase 1 antigen may be elevated or rise as well); OR
Detection of C burnetii DNA in a clinical specimen via amplification of a specific target by polymerase chain reaction (PCR) assay; OR
Demonstration of C burnetii in a clinical specimen by immunohistochemical methods (IHC); OR
Isolation of C burnetii from a clinical specimen by culture.
Laboratory supportive
Single supportive IFA IgG titre of ≥1:128 to phase 2 antigen (phase 1 titres may be raised as well).
Serological evidence of elevated phase 2 IgG or IgM antibody reactive with C burnetii antigen by enzyme-linked immunosorbent assay (ELISA), dot-ELISA, or latex agglutination.
Case classification
Probable: a clinically compatible case of acute illness (meets clinical evidence criteria for acute Q fever illness) that has laboratory supportive results for past or present acute disease (antibody to phase 2 antigen) but is not laboratory confirmed.
Confirmed: a laboratory confirmed case that either meets clinical case criteria or is epidemiologically linked to a laboratory confirmed case.
CDC: Q fever (Coxiella burnetii) 2009 case definition Opens in new window
Centers for Disease Control and Prevention (CDC): Q fever (Coxiella burnetii) 2009 case definition - chronic[84]
Clinical criteria
Infection that persists for more than 6 months.
Newly recognised, culture-negative endocarditis, particularly in a patient with previous valvulopathy or compromised immune system, suspected infection of a vascular aneurysm or vascular prosthesis, or chronic hepatitis, osteomyelitis, osteoarthritis, or pneumonitis in the absence of other known aetiology.
Laboratory criteria
Serological evidence of IgG antibody to C burnetii phase 1 antigen ≥1:800 by IFA (while phase 2 IgG titre will be raised as well; phase 1 titre is higher than the phase 2 titre); OR
Detection of C burnetii DNA in a clinical specimen via amplification of a specific target by PCR assay; OR
Demonstration of C burnetii antigen in a clinical specimen by IHC; OR
Isolation of C burnetii from a clinical specimen by culture.
Laboratory supportive
Has an antibody titre to C burnetii phase 1 IgG antigen ≥1:128 and <1:800 by IFA.
Case classification
Probable: a clinically compatible case of chronic illness (meets clinical evidence criteria for chronic Q fever) that has laboratory supportive results for past or present chronic infection (antibody to phase 1 antigen).
Confirmed: clinically compatible case of chronic illness (meets clinical evidence criteria for chronic Q fever) that is laboratory confirmed for chronic infection.
CDC: Q fever (Coxiella burnetii) 2009 case definition Opens in new window
Criteria for the diagnosis of Coxiella burnetii primary infection based on acute symptoms and history of valvulopathy, immunodeficiency, or pregnancy[44]
Acute Q fever:
Fever, hepatitis and/or pneumonia with microbiological criteria (phase 2 IgG ≥1:200 and phase 2 IgM ≥1:50, seroconversion, or a positive polymerase chain reaction [PCR] on blood/serum and no endocarditis)
Duration of symptoms <3 months after symptoms onset or seroconversion.
Acute Q fever with significant valvulopathy:
Criteria for acute Q fever plus history of rheumatic fever, bicuspid aortic valve, congenital heart disease, prosthetic heart valves, valve regurgitation, stenosis grade ≥II, mitral valve prolapse.
Acute Q fever with significant vasculopathy:
Criteria for acute Q fever plus history of vascular graft or vascular aneurysm.
Acute Q fever with severe immunodeficiency:
Criteria for acute Q fever in transplant patients, patients undergoing chemotherapy or corticosteroid therapy, patients with HIV with <200 CD4, patients with haematological malignancies.
Asymptomatic primary infection with C burnetii during pregnancy:
Asymptomatic pregnant woman with both phase 2 IgG ≥1:200 and IgM ≥1:50.
Criteria for the diagnosis of C burnetii endocarditis[85]
A. Definite criteria:
Positive culture
PCR or immunochemistry of a cardiac valve.
B. Major criteria:
Microbiology: positive culture or PCR of the blood or emboli, or serology with phase 1 IgG antibodies ≥1:6400
Evidence of endocardial involvement:
Echocardiogram positive for infective endocarditis: oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets, or on implanted material in the absence of an alternative anatomical explanation; or abscess; or new partial dehiscence of prosthetic valve; or new valvular regurgitation (worsening or changing of pre-existing murmur not sufficient)
PET scan showing a specific valve fixation and mycotic aneurysm.
C. Minor criteria:
Predisposing heart condition (known or found on echography)
Fever (>38°C)
Vascular phenomena, major arterial emboli, septic pulmonary infarcts, mycotic aneurysm (at PET scan), intracranial haemorrhage, conjunctival haemorrhages, and Janeway’s lesions
Immunological phenomena: glomerulonephritis, Osler’s nodes, Roth's spots, or rheumatoid factor
Positive serology with phase 1 IgG antibodies ≥1:800 and <1:6400.
Definite diagnosis:
One A criterion
Two B criteria
One B criterion and three C criteria (including evidence of microbiology and cardiac predisposition).
Possible diagnosis:
One B criterion and two C criteria (including evidence of microbiology and cardiac predisposition)
Three C criteria (including positive serology and cardiac predisposition).
Patients meeting the criteria for definite or possible C burnetii endocarditis on prosthetic heart valve or pacemaker, or following Bentall surgery, should be diagnosed as having definite or possible foreign body-related endocarditis, respectively, and should be treated accordingly (i.e., 24-month treatment course).
Patients with severe heart valve disease (generally in a cardiac surgery unit) have been diagnosed with definite endocarditis with phase 1 IgG levels as low as 1:200.[57][60] In this specific context (cardiac surgery and vascular surgery and very low serological titres between 1:200 and 1:400), treatment of endocarditis and vascular infection must be prescribed even in the absence of infectious symptoms or a positive PCR since mortality risk is high if left untreated.
Criteria for diagnosis of C burnetii vascular infection[85]
A. Definite criteria:
Positive culture
PCR or immunochemistry of an arterial sample (prosthesis or aneurysm) or a periarterial abscess, or a spondylodiscitis linked to aorta.
B. Major criteria:
Microbiology: positive culture, PCR of the blood or emboli, or serology with phase 1 IgG antibodies ≥1:6400
Evidence of vascular involvement:
CT scan: aneurysm or vascular prosthesis, and periarterial abscess, fistula, or spondylodiscitis
PET scan: specific fixation on an aneurysm or vascular prosthesis.
C. Minor criteria:
Positive serology with phase 1 IgG antibodies ≥1:800 and <1:6400
Fever (≥38°C)
Emboli
Underlying vascular predisposition (e.g., aneurysm or vascular prosthesis).
Definite diagnosis:
One A criterion
Two B criteria
One B criterion and two C criteria (including evidence of microbiology and vascular predisposition).
Possible diagnosis:
Vascular predisposition, serological evidence, and fever or emboli.
Patients meeting the criteria for definite or possible C burnetii vascular infection on vascular prosthetic material should be diagnosed as having definite or possible foreign-body related vascular infection, and should be treated accordingly (i.e., 24-month treatment course).
Criteria for diagnosis of C burnetii prosthetic joint infection[86]
A. Definite criteria:
Positive culture
PCR or immunochemistry of a periprosthetic biopsy or joint aspirate.
B. Major criteria:
Microbiology:
Positive culture, or PCR of the blood
Positive C burnetii serology with phase 1 IgG antibodies ≥1:6400
Evidence of prosthetic involvement:
CT scan or MRI positive for prosthetic infection: collection or pseudotumour of the prosthesis
PET scan or indium leukocyte scan showing a specific prosthetic hypermetabolism consistent with infection
For the 18F-fluorodeoxyglucose PET scan, the uptake at the bone-prosthesis interface with exclusion of the head and tip is considered the best criterion for infection, with 92% sensitivity and 97% specificity.
C. Minor criteria:
Presence of a joint prosthesis (indispensable criteria)
Fever (≥38°C)
Joint pain
Positive serology with phase 1 IgG antibodies >1:800 and <1:6400.
Definite diagnosis:
One A criterion
Two B criteria
One B criterion and three C criteria (including evidence of microbiology and presence of a joint prosthesis).
Possible diagnosis:
One B criterion and two C criteria (including evidence of microbiology and presence of a joint prosthesis)
Three C criteria (including positive serology and presence of a joint prosthesis).
Criteria for diagnosis of C burnetii osteoarticular infection without prosthesis[3][80]
A. Definite criteria:
Positive culture
PCR or immunochemistry of bone or synovial biopsy or joint aspirate.
B. Major criteria:
Microbiology:
Positive culture or positive PCR of the blood
Positive serology with phase 1 IgG antibodies ≥1:800
Evidence of bone or joint involvement:
Clinical arthritis, osteitis, or tenosynovitis
CT scan or ultrasonography (for joint) or MRI: osteoarticular destruction, joint effusion, intra-articular collection, spondylodiscitis, synovitis, acromioclavicular localisation
PET scan or indium leukocyte scan showing a specific osteoarticular uptake.
C. Minor criteria:
Positive serology with phase 1 IgG antibodies ≥1:400 and <1:800
Fever (≥38°C)
Mono- or polyarthralgia.
Definite diagnosis:
One A criterion
Two B criteria
One B criterion and three C criteria (including one microbiological characteristic).
Possible diagnosis:
One B criterion and two C criteria
Three C criteria.
Criteria for diagnosis of C burnetii chronic lymphadenitis[3][80]
A. Definite criteria:
Positive culture
PCR or immunohistochemistry or fluorescence in situ hybridisation (FISH) of lymphadenitis.
B. Major criteria:
Microbiology:
Positive culture, or positive PCR of the blood
Positive serology with phase 1 IgG antibodies ≥1:800
Evidence of lymph node involvement:
Clinical lymphadenitis
CT scan or ultrasonography (for joint) or MRI: lymphadenitis >1 cm
PET scan showing specific lymph node uptake.
C. Minor criteria:
Positive serology with phase 1 IgG antibodies ≥1:400 and <1:800
Fever (≥38°C).
Definite diagnosis:
One A criterion
Two B criteria
One B criterion and two C criteria (including one microbiological characteristic).
Possible diagnosis:
One B criterion and one C criterion
Two C criteria.
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