J Peter Donnelly

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The revised EORTC/MSG definitions - DEF II

• J Peter Donnelly
• Department of Haematology
• Nijmegen University Centre for Infectious Diseases

University Medical Centre St Radboud, Radboud
University Nijmegen Netherlands
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• Why revise?
• The process
• Definitions II

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• Why revise?
• The process
• Definitions II

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EORTC-IFICG NIAID-MSG
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GOAL OF ADAPTING DEFINITIONS
present
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Problems with Definitions I
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EORTC/MSG definitions - aspergillosis
Clinical features
Host factor
Mycology


HSCT
antigenaemia
Halo sign on CT scan
Probable
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EORTC/MSG definitions - aspergillosis
Clinical features
Host factor
Mycology


HSCT
none
Halo sign on CT scan
possible
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Question
Host factor
neutropenic

Clinical features
Halo sign on pulmonary CT
Diagnosis?

Mycology
Blood BAL Galactomannan negative
Blood PCR positive
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Question

• The patient has a possible invasive
  aspergillosis.
• The patient has a probable invasive
  aspergillosis.
• The patient has a proven invasive aspergillosis.
• The patient has a possible invasive fungal
  infection.

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Answer
Host factor
neutropenic

possible invasive fungal infection
Clinical features
Halo sign on pulmonary CT

Mycology
Blood BAL Galactomannan negative
Blood PCR positive
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• Why revise?
• The process
• Definitions II

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ICAAC 43 Chicago 2003

• the need for the rules for defining IFI to be
  clear and consistent was of paramount importance
• proven invasive fungal infection (IFI) does not
  require the presence of a host factor as such
• for probable IFI the host factors should be
  expanded to include
• solid organ transplants
• HIV infection
• hereditary immunodeficiencies
• connective tissue disorders
• low birth-weight (lt1500 g) infants
• diabetes mellitus
• immunopharmacological treatments e.g. infliximab,
  dicluzimab, fludarabine

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ICAAC 43 Chicago 2003

• e) PROVEN, PROBABLE and POSSIBLE should remain as
  categories for IFI
• f) probable IFI will continue to require that all
  three elements should be present and therefore is
  defined as host factors AND clinical features AND
  mycological evidence
• g) the definitions for proven IFI will remain
  unchanged. The principle is that the criteria for
  proven or probable IFI have to be met in full in
  order to assign a level of certainty.

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ICAAC 43 Chicago 2003 - working parties
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ICAAC 43 Chicago 2004 - working parties
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• The best laid schemes o' Mice an' Men,
• Gang aft agley,
• An' lea'e us nought but grief an' pain,
• For promis'd joy!
• (The best laid schemes of Mice and Men
• oft go awry,
• And leave us nothing but grief and pain,
• For promised joy!)

Robert Burns (1759 - 1796) To a Mouse
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Head to head
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Plan B
Microbiological Criteria.doc
Proven IFI.doc
Host factors.doc
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Round 1
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Round 2
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Definitions II process
Round 1
Round 6
Round 2
Round 5
Round 3
Round 4
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(No Transcript)
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• Why revise?
• The process
• Definitions II

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First change
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Whatss in a name?

• Invasive Fungal Infection
• Invasive Fungal Disease

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No change
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Proven invasive fungal infective disease
Mycology
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ICAAC 43 Chicago 2003
definitions for proven IFI

• e.g.
• mould detected histologically
• not recovered by culture
• galactomannan antigen is detected

proven mycosis
probably aspergillosis
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Defining probable invasive fungal disease
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Second change
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Definitions I - Possible invasive fungal disease
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Invasive fungal disease - Definitions I
tissue
Mycology
Clinical features
Host factors



Proven
Mycology
Clinical features
Host factors
Probable



Clinical features
Host factors
Negative or Not done


Clinical features
Host factors
Possible
Negative or Not done


Host factors
Mycology


none
Host factors
Negative or Not done

Not classified
none
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Invasive fungal disease - Definitions II
tissue
Mycology
Clinical features
Host factors



Proven
Mycology
Clinical features
Host factors
Probable



Clinical features
Host factors
Negative or Not done


Possible
Clinical features
Host factors
Negative or Not done


Host factors
Mycology


none
Not classified
Host factors
Negative or Not done

none
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Invasive fungal disease - Definitions II
tissue
Mycology
Clinical features
Host factors



Proven
Mycology
Clinical features
Host factors
Probable



Clinical features
Host factors
Negative or Not done


Possible
Clinical features
Host factors
Negative or Not done


Not classified
Host factors
Mycology


none
Host factors
Negative or Not done

none
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Definitions II - Possible invasive fungal disease
Characteristic of invasive fungal disease BUT
no mycological evidence

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Third change
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Definitions I - Host factors
neutropenia
gt 3 weeks corticosteroids

• lt36C or gt 38C and
• prior mycosis
• AIDS
• Immunosuppressive drugs
• gt 10 days neutropenia

gt 4 days unexplained fever despite broad spectrum
antibiotics
Graft versus Host Disease
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Definitions II - Host factors
neutropenia
neutropenia
gt 3 weeks corticosteroids
gt 3 weeks corticosteroids
Allogeneic HSCT recipient

• lt36C or gt 38C and
• prior mycosis
• AIDS
• Immunosuppressive drugs
• gt 10 days neutropenia

gt 4 days unexplained fever despite broad spectrum
antibiotics
Treatment with other recognized T-cell immune
suppressants
Inherited severe immunodeficiency
Graft versus Host Disease
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Fourth change
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Definitions I - Clinical features
MAJOR
1
Lower respiratory tract infection
Chronic disseminated candidiasis
Halo sign Air-crescent sign cavity
Bulls eye lesions in liver or spleen
Sinonasal infection
Radiological evidence
CNS infection
Disseminated fungal infection
Radiological evidence
Unexplained papular or nodular skin
lesions Chorioretinitis endophthalmitis
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Definitions I - Clinical features
2
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Definitions II - Clinical features
Lower respiratory tract infection
Chronic disseminated candidiasis
Sinonasal infection
CNS infection
No more major and no more minor All in the same
key now
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Definitions II - Clinical features
Lower respiratory tract infection

• A) the presence of one of the following
  specific imaging signs on CT-
• Well defined nodule(s) with a halo sign
• Well defined nodule(s) without a halo sign
• Wedge-shaped infiltrate
• Air crescent sign
• Cavity

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Specific pulmonary infiltrates on CT scan
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Definitions II - Clinical features
Lower respiratory tract infection

• B) the presence of a new non-specific focal
  infiltrate
• PLUS at least one of the following-
• Pleural rub
• Pleural pain
• Hemoptysis

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Definitions II - Clinical features
sinonasal infection

• Imaging showing sinusitis
• PLUS
• at least one of the following-
• Acute localized pain (including pain radiating to
  eye)
• Nasal ulcer, black eschar
• Extension from the paranasal sinus across bony
  barriers, including into the orbit

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Definitions II - Clinical features
CNS infection

• at least one of the following-
• Focal lesions on imaging
• Meningeal enhancement on MRI or CT

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Definitions II - Clinical features
Chronic disseminated candidiasis
Small, peripheral, target like abscesses (new
nodular filling defects, bulls-eye lesions) in
liver and/or spleen
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Fifth change
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Definitions I - Mycology
Culture of mould from tissue. aspirate BAL or
sputum
antigen in blood, BAL. CSF
mould seen in sinus aspirate
Fungi seen in tissue or sterile body fluids
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Definitions II - Mycology
antigen in blood, BAL. CSF
Culture of mould from tissue. aspirate BAL or
sputum
mould seen in sinus aspirate
Beta-D-glucan in BAL. CSF or blood
Fungi seen in tissue or sterile body fluids
PCR to detect nucleic acid
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EORTC/MSGDefinitions for invasive fungal disease
Thanks To the consensus group To the
organizers And to you the audience