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The importance of epidemiology The importance of epidemiology in the diagnosis of invasive in the diagnosis of invasive
fungal infectionsfungal infections
J Peter Donnelly BSc PhDJ Peter Donnelly BSc PhD
Department of HaematologyDepartment of HaematologyUniversity Medical Centre St RadboudUniversity Medical Centre St Radboud
Nijmegen, The NetherlandsNijmegen, The Netherlands
Some issuesSome issues
Microscopy and culture are essentially unavailable to microbiologists Microscopy and culture are essentially unavailable to microbiologists with respect to invasive fungal infections (IFI)with respect to invasive fungal infections (IFI)
BecauseBecause
• IFI commonly affects the lungs initially but cases can easily go IFI commonly affects the lungs initially but cases can easily go unnoticedunnoticed
• Even when recognized early, suitable specimens can be difficult Even when recognized early, suitable specimens can be difficult to obtain to obtain
• Tests for detecting fungal pathogens in clinical material Tests for detecting fungal pathogens in clinical material (particularly blood) are available, but there is no consensus (particularly blood) are available, but there is no consensus about their clinical utilityabout their clinical utility
HenceHence
many expect nothing from diagnosis and do not even attempt to make many expect nothing from diagnosis and do not even attempt to make one. The resulting lack of adequate diagnoses makes estimating the one. The resulting lack of adequate diagnoses makes estimating the prevalence and incidence of IFI unreliable.prevalence and incidence of IFI unreliable.
EpidemiologyEpidemiology
This dismal state of affairs serves only to This dismal state of affairs serves only to emphasize the importance of epidemiology emphasize the importance of epidemiology since, in order to determine the value of any since, in order to determine the value of any diagnostic test or battery of tests, one has to diagnostic test or battery of tests, one has to know the underlying prevalence of the disease, know the underlying prevalence of the disease, particularly when this is low.particularly when this is low.
The first questions are:-The first questions are:-
• Who gets IFI? Who gets IFI?
• What do they get and how?What do they get and how?
• When do they get?When do they get?
Who gets IFI?Who gets IFI?
Candidaemia in French hospitalsCandidaemia in French hospitals
originorigin central linecentral line 26%26% digestive tractdigestive tract 11%11% unknownunknown 43%43%
Incidence/ 1000 admissionsIncidence/ 1000 admissionsTotal Total 0.290.29General hospitalGeneral hospital 0.170.17Teaching hospitalTeaching hospital 0.380.38Cancer centerCancer center 0.710.71
Andremont et al, ICAAC 1998, San Diego
parapsilosisparapsilosis
glabrataglabratatropicalistropicalis
albicansalbicans
kruseikrusei
Risk factorRisk factor CancerCancer ICUICU
Neutropenia, HSCT, chemotherapy,Neutropenia, HSCT, chemotherapy,
GvHD, mucosal barrier injuryGvHD, mucosal barrier injury
Candida colonisationCandida colonisation
Broad-spectrum antibioticsBroad-spectrum antibiotics
Haemodialysis, azotemiaHaemodialysis, azotemia
Central venous catheterCentral venous catheter
Severity of illnessSeverity of illness
HyperalimentationHyperalimentation
Recurrent/persistent GI tract perforation Recurrent/persistent GI tract perforation
Prior surgeryPrior surgery
Neonatal ICU (age, low APGAR,Neonatal ICU (age, low APGAR,
LOS, shock, H2 blockers, intubation)LOS, shock, H2 blockers, intubation)
Rex & Sobel Clin Infect Dis 2001 32;1191
Risk factors for invasive candidosisRisk factors for invasive candidosis
Incidence of invasive fungal infections among Incidence of invasive fungal infections among solid organ transplant recipientssolid organ transplant recipients
TransplantTransplant IFIIFI
RenalRenal 1.4 - 141.4 - 14
HeartHeart 5 - 215 - 21
LiverLiver 7 - 427 - 42
Lung & heart/lungLung & heart/lung 15 - 3515 - 35
Small bowelSmall bowel 40 - 5940 - 59
Pancreas Pancreas 18 - 3818 - 38
AspergillusAspergillus CandidaCandida
Singh Clin Infect Dis. 2001 31: 545
Timing of fungal infections after solid organ transplantTiming of fungal infections after solid organ transplant
11 22 33 44 55 66 77 88
CMVCMV
CandidaCandida
AspergillusAspergillus
CryptococcusCryptococcus
Endemic fungiEndemic fungi
PneumocystisPneumocystis
Snydman Clin Infect Dis. 2001 33: S5
00
Incidence of fatal fungal infections amongst Incidence of fatal fungal infections amongst patients other than those with HIV in the USApatients other than those with HIV in the USA
Mc Neil et al 2001 Clin Infect Dis 33;641
Candidiasis
AspergillosisAspergillosis
0%0% 53%53%
Acute InvasiveAcute Invasive
CandidiasisCandidiasis
Acute InvasiveAcute Invasive
CandidiasisCandidiasis
81 patients81 patients
4646
NO YES
BacteraemiaBacteraemia
++++++++ColonisationColonisationColonisationColonisation
Guiot et al, Clin Infect Dis 1994; 18:525-32 641
Invasive candidiasis, colonisation and bacteraemiaInvasive candidiasis, colonisation and bacteraemia
1414 2424 88 77 1313 1515
3535
11 00 00 00 11 88
- - - - ++++ ++++++++ - - - - ++++
Risk groupRisk group ColonisationColonisation Mucosal barrier injuryMucosal barrier injury TreatmentTreatment
LowLow nono nono nono
Intermediate Intermediate nono yesyes nono
yesyes nono yes or no*yes or no*
High riskHigh risk yesyes yesyes yesyes
MBI and invasive MBI and invasive CandidaCandida infections infections
* depending on other predisposing factors* depending on other predisposing factors
Invasive aspergillosis and underlying diseaseInvasive aspergillosis and underlying disease
ConditionCondition range (%)range (%)
Chronic granulomatous diseaseChronic granulomatous disease 25-4025-40
Lung ± heart transplantLung ± heart transplant 19-2619-26
Liver transplantLiver transplant 1.5-101.5-10
Heart & renal transplantHeart & renal transplant 0.5-100.5-10
AIDSAIDS 0-120-12
SCIDSCID 3.53.5
BurnsBurns 1-71-7
SLESLE 11
Acute leukaemiaAcute leukaemia 5-245-24
Allogeneic HSCTAllogeneic HSCT 4-94-9
Autologous HSCT (no growth factors)Autologous HSCT (no growth factors) 0.5-60.5-6
Autologous HSCT (with growth factors)Autologous HSCT (with growth factors) <1<1
Denning Clin Infect Dis 2001 26 pp781-805
0 10 20 30 40%0 10 20 30 40%
haematopoietic haematopoietic stem cell stem cell
transplanttransplant
Denning. Clin Inf Dis 1998
autologousautologous
Incidence of invasive aspergillosis under Incidence of invasive aspergillosis under various conditionsvarious conditions
heartheart/heart-lung transplant/heart-lung transplant
chronic granulomatous diseasechronic granulomatous disease
acute leukemiaacute leukemia
allogeneicallogeneic
solid organ transplantsolid organ transplant
AIDSAIDS
+ growth factor+ growth factor
Transplant typeTransplant type incidence (%)incidence (%)
LungLung 8.4 8.4
Haematopoietic stem cellHaematopoietic stem cell 6.4 6.4AutologousAutologous 2.6 2.6AllogeneicAllogeneic
Related donorRelated donor 6.7 6.7Unrelated donor Unrelated donor 10.310.3
HeartHeart 6.2 6.2
LiverLiver 1.7 1.7
PancreasPancreas 1.3 1.3
KidneyKidney 0.7 0.7
Transplant typeTransplant type incidence (%)incidence (%)
LungLung 8.4 8.4
Haematopoietic stem cellHaematopoietic stem cell 6.4 6.4AutologousAutologous 2.6 2.6AllogeneicAllogeneic
Related donorRelated donor 6.7 6.7Unrelated donor Unrelated donor 10.310.3
HeartHeart 6.2 6.2
LiverLiver 1.7 1.7
PancreasPancreas 1.3 1.3
KidneyKidney 0.7 0.7
Paterson et al. Medicine 1999;78:123-38.
Incidence of invasive aspergillosis in transplant Incidence of invasive aspergillosis in transplant recipientsrecipients
Aspergillosis at autopsy - sites of infectionAspergillosis at autopsy - sites of infection
aspergillosiaspergillosiss
Lungs onlyLungs only
CNS onlyCNS onlyDisseminatedDisseminated(not lungs) (not lungs)
Disseminated Disseminated
Vogeser et al Eur J Clin Microbiol Infect Dis 1999;18; 42-45
1187 autopsies 1993 - 19961187 autopsies 1993 - 199648 (4%) aspergillosis48 (4%) aspergillosis
Explaining the current trends in opportunistic Explaining the current trends in opportunistic fungal infectionsfungal infections
Singh Clin Infect Dis 2001 33;1692
Increase in number of susceptible hostsIncrease in number of susceptible hosts
New medical methods New medical methods
• HSCT - CD 34HSCT - CD 34++ selection selection
• Advances in surgical techniques for solid transplantAdvances in surgical techniques for solid transplant
• immunesuppressive regimens for solid transplantimmunesuppressive regimens for solid transplant
• More conservative approach More conservative approach • Less use of corticosteroidsLess use of corticosteroids• Use of novel agentsUse of novel agents
Antimicrobial prophylaxisAntimicrobial prophylaxis
• Fluoroquinolones for Gram negative bacilliFluoroquinolones for Gram negative bacilli• Fluconazole for Fluconazole for CandidaCandida• Ganciclovir for CMVGanciclovir for CMV
Improved laboratory expertiseImproved laboratory expertise
• detection detection • identificationidentification
Invasive fungal infections
Haematological malignancyHaematological malignancy
Allogeneic HSCTAllogeneic HSCT
ICUICU
CGDCGD
BurnsBurns
LiverLiver
HeartHeart
TransplantTransplant
RenalRenal
LungLung
Who gets IFI?Who gets IFI?
HIVHIV
What do they get and how?What do they get and how?
The main playersThe main players
Hi Bud!
Hi pal!
Huh. You guys get all
the attention
How do they get it?How do they get it?
Candida - colonisationCandida - colonisation
Candida parapsilosisCandida parapsilosisCandida albicansCandida albicans
Candida parapsilosisCandida parapsilosisCandida albicansCandida albicans
Candida albicansCandida albicansCandida tropicalisCandida tropicalis
Candida albicansCandida albicansCandida tropicalisCandida tropicalis
Candida albicansCandida albicansCandida glabrataCandida glabrata
Candida kruseiCandida krusei
Candida albicansCandida albicansCandida glabrataCandida glabrata
Candida kruseiCandida krusei
GI tractGI tract
antibioticsinsult
injury selection
translocationtranslocation
infectioninfection CandidaCandida species species
Normal Normal commensal commensal floraflora
DiseaseDisease
Model for invasive candidiasisModel for invasive candidiasis
AspergillosisAspergillosis
Aspergillus from the breeze or the bucketAspergillus from the breeze or the bucket
Graybill Clin Infect Dis 2001 26 pp781-805
What do they get and how ?What do they get and how ?
• MainlyMainly Candida albicans Candida albicans oror Aspergillus Aspergillus fumigatusfumigatus
• prior colonisation with Candida species is a prior colonisation with Candida species is a prerequisite for infectionprerequisite for infection
• Spores of Spores of AspergillusAspergillus and other moulds are and other moulds are inhaled directly through the air or indirectly inhaled directly through the air or indirectly from aerosols of contaminated waterfrom aerosols of contaminated water
When do they get it?When do they get it?
days after transplantdays after transplant
1010 2020 3030 4040 5050 6060 7070 8080 9090 100100 110110 120120 130130 140140 150150 160160 170170 180180 >180>180
Cas
esC
ases
2020
1818
1616
1414
1212
1010
88
66
44
22
00
Wald et al J Infect Dis 1997:175;1459
Time to diagnosis of aspergillosis after BMTTime to diagnosis of aspergillosis after BMT
Aspergillosis following HSC transplantAspergillosis following HSC transplantG
ran
ulo
cyte
s (lo
gG
ran
ulo
cyte
s (lo
g 1010
1x
10
1x
1066 /
L)
/L)
0.10.1
11
1010
3636
3737
3838
3939
4040
4141
Te
mp
era
ture
°C
Te
mp
era
ture
°C
DaysDays MonthsMonths
-7-7 00 77 1414 2121 1212 66 99 1212-14-14 662828 88 1010
WeeksWeeksTransplantTransplant
ENGRAFTMENTENGRAFTMENTENGRAFTMENTENGRAFTMENTPRE-PRE-TRANSPLANTTRANSPLANTPRE-PRE-TRANSPLANTTRANSPLANT
EARLY POST-ENGRAFTMENTEARLY POST-ENGRAFTMENTEARLY POST-ENGRAFTMENTEARLY POST-ENGRAFTMENT LATE POST-ENGRAFTMENTLATE POST-ENGRAFTMENTLATE POST-ENGRAFTMENTLATE POST-ENGRAFTMENT
Stem cellsStem cells acute GvHDacute GvHD low IgGlow IgGchronic GvHDchronic GvHD
neutropenianeutropenia corticosteroidscorticosteroids
Source of stem cells and GVHDSource of stem cells and GVHD
Cutler et al 2002 J Clin Oncol 19:3685-3691
Source of stem cells and GVHDSource of stem cells and GVHD
Cutler et al 2002 J Clin Oncol 19:3685-3691
FEVERFEVER
ALKALINE PHOSPHATASEALKALINE PHOSPHATASE
NEUTROPHILSNEUTROPHILS
DISSEMINATIONDISSEMINATION MICROCOLONIESMICROCOLONIES "BULLS EYE""BULLS EYE"
HEPATOSPLENIC CANDIDIASISHEPATOSPLENIC CANDIDIASIS
when do they get? when do they get?
• Both candidiasis and aspergillosis occur during Both candidiasis and aspergillosis occur during neutropenia but also manifest themselves later neutropenia but also manifest themselves later after bone marrow recovery.after bone marrow recovery.
• Patients are at risk of aspergillosis for as long Patients are at risk of aspergillosis for as long as they have active GvHD or are receiving high as they have active GvHD or are receiving high dose corticosteroidsdose corticosteroids
DiagnosisDiagnosis
Sites of infectionSites of infection
Candida albicansCandida albicans
Candida glabrataCandida glabrata
Candida kruseiCandida krusei
Candida albicansCandida albicans
Candida glabrataCandida glabrata
Candida kruseiCandida krusei
Candida parapsilosisCandida parapsilosis
Candida albicansCandida albicans
Candida parapsilosisCandida parapsilosis
Candida albicansCandida albicans
Candida albicansCandida albicans
Candida tropicalisCandida tropicalis
Candida albicansCandida albicans
Candida tropicalisCandida tropicalis
MouldsMouldsMouldsMouldsYeastYeastYeastYeast
Aspergillus fumigatusAspergillus fumigatusAspergillus fumigatusAspergillus fumigatus
MucorMucorMucorMucor
Fusarium speciesFusarium speciesFusarium speciesFusarium species
Defining invasive fungal infectionDefining invasive fungal infection
Host factor
Clinical feature
Mycology
Invasive Fungal Infections Cooperative Group
MycosesMycosesStudyStudyGroupGroup
MycosesMycosesStudyStudyGroupGroup
Ascioglu et al 2002Clin Infect Dis 34:7-14
Defining infection - Host factorsDefining infection - Host factors
Host factor
neutropenianeutropenianeutropenianeutropenia
> 4 days unexplained > 4 days unexplained fever despite broad fever despite broad spectrum antibioticsspectrum antibiotics
> 4 days unexplained > 4 days unexplained fever despite broad fever despite broad spectrum antibioticsspectrum antibiotics
Graft versus Host DiseaseGraft versus Host DiseaseGraft versus Host DiseaseGraft versus Host Disease
> 3 weeks corticosteroids> 3 weeks corticosteroids> 3 weeks corticosteroids> 3 weeks corticosteroids
<36°C or > 38°C and <36°C or > 38°C and • prior mycosisprior mycosis• AIDSAIDS• ImmunosuppressivesImmunosuppressives• > 10 days neutropenia> 10 days neutropenia
<36°C or > 38°C and <36°C or > 38°C and • prior mycosisprior mycosis• AIDSAIDS• ImmunosuppressivesImmunosuppressives• > 10 days neutropenia> 10 days neutropenia
Invasive Fungal Infections Cooperative Group
MycosesMycosesStudyStudyGroupGroup
MycosesMycosesStudyStudyGroupGroup
Ascioglu et al 2002Clin Infect Dis 34:7-14
Defining infection - Clinical featuresDefining infection - Clinical features
Clinical feature
Invasive Fungal Infections Cooperative Group
MycosesMycosesStudyStudyGroupGroup
MycosesMycosesStudyStudyGroupGroup
Halo signHalo signAir-crescent signAir-crescent signcavitycavity
Lower respiratory tract infectionLower respiratory tract infectionLower respiratory tract infectionLower respiratory tract infection
Sinonasal infectionSinonasal infectionSinonasal infectionSinonasal infection
CNS infectionCNS infectionCNS infectionCNS infection Disseminated fungal infectionDisseminated fungal infectionDisseminated fungal infectionDisseminated fungal infection
Chronic disseminated candidiasisChronic disseminated candidiasisChronic disseminated candidiasisChronic disseminated candidiasis
Radiological evidenceRadiological evidence
Radiological evidenceRadiological evidence Unexplained papular or nodular skin lesionsUnexplained papular or nodular skin lesionsChorioretinitisChorioretinitisendophthalmitisendophthalmitis
Bull’s eye lesions in liver or spleenBull’s eye lesions in liver or spleen
MAJORMAJOR
Ascioglu et al 2002Clin Infect Dis 34:7-14
Defining infection - Clinical featuresDefining infection - Clinical features
Clinical feature
Invasive Fungal Infections Cooperative Group
MycosesMycosesStudyStudyGroupGroup
MycosesMycosesStudyStudyGroupGroup
Cough, chest pain, haemoptysis, dyspnoeaCough, chest pain, haemoptysis, dyspnoeaPhysical finding of pleural rubPhysical finding of pleural rubAny new infiltrate not fulfilling major criterion Any new infiltrate not fulfilling major criterion
Lower respiratory tract infectionLower respiratory tract infectionLower respiratory tract infectionLower respiratory tract infection
Sinonasal infectionSinonasal infectionSinonasal infectionSinonasal infection
CNS infectionCNS infectionCNS infectionCNS infection
Nasal discharge, stuffinessNasal discharge, stuffinessNose ulceration, eschar or epistaxisNose ulceration, eschar or epistaxisPeriorbital swellingPeriorbital swellingMaxillary tendernessMaxillary tendernessBlack necrotic lesions or perforation of the hard-palateBlack necrotic lesions or perforation of the hard-palate
CSFCSF No pathogensNo pathogensno malignant cellsno malignant cellsabnormal biochemistryabnormal biochemistryabnormal cell countabnormal cell count
Focal neurological Focal neurological seizuresseizureshemiparesishemiparesiscranial nerve palsycranial nerve palsy
Mental changesMental changesMeningeal irritationMeningeal irritation
MINORMINOR
Ascioglu et al 2002Clin Infect Dis 34:7-14
Defining infection - MycologyDefining infection - Mycology
Mycology
antigen in BAL, CSF or bloodantigen in BAL, CSF or blood
Culture of mould from tissue, aspirate BAL or sputum Culture of mould from tissue, aspirate BAL or sputum
mould seen in sinus aspiratemould seen in sinus aspirate
Fungi seen in tissue or sterile body fluidsFungi seen in tissue or sterile body fluids
Invasive Fungal Infections Cooperative Group
MycosesMycosesStudyStudyGroupGroup
MycosesMycosesStudyStudyGroupGroup
Ascioglu et al 2002Clin Infect Dis 34:7-14
Proven invasive fungal infective diseaseProven invasive fungal infective disease
Host factor
Clinical features++ Tissue++ Mycology++
Invasive Fungal Infections Cooperative Group
MycosesMycosesStudyStudyGroupGroup
MycosesMycosesStudyStudyGroupGroup
Ascioglu et al 2002Clin Infect Dis 34:7-14
Host factor
Probable invasive fungal infective diseaseProbable invasive fungal infective disease
Clinical features++ Mycology++
Invasive Fungal Infections Cooperative Group
MycosesMycosesStudyStudyGroupGroup
MycosesMycosesStudyStudyGroupGroup
Ascioglu et al 2002Clin Infect Dis 34:7-14
Possible invasive fungal infective diseasePossible invasive fungal infective disease
Host factor
Clinical features
++
Mycology
OROR
Invasive Fungal Infections Cooperative Group
MycosesMycosesStudyStudyGroupGroup
MycosesMycosesStudyStudyGroupGroup
Ascioglu et al 2002Clin Infect Dis 34:7-14
Mycology
EORTC/MSG definitions of fungal infections -EORTC/MSG definitions of fungal infections -aspergillosisaspergillosis
Host factor
Clinical features
Halo sign on chest CT scanHalo sign on chest CT scan
coughcough
pleural rubpleural rub
antigenaemiaantigenaemiaGVHD GVHD
OR
++
++ ++
Probable disease
Probable disease
EORTC/MSG definitions of fungal infections -EORTC/MSG definitions of fungal infections -candidosiscandidosis
elevated alkaline phosphataseelevated alkaline phosphatase
Small, peripheral, target-like abscesses Small, peripheral, target-like abscesses (Bull’s eye) in liver and/or spleen (Bull’s eye) in liver and/or spleen demonstrated by CT, MRI or ultra demonstrated by CT, MRI or ultra sonogram.sonogram.
NeutropeniaNeutropenia ++
+/-+/-
Host factor
Clinical features Mycology
Probable disease
Probable disease
Strategy Strategy
includeinclude all patients likely to have aspergillosis and all patients likely to have aspergillosis and treat them treat them pre-emptivelypre-emptively with the safest with the safest and most effective drugand most effective drug
Aim of the strategyAim of the strategy
ANDAND
excludeexclude all patients unlikely to have the disease all patients unlikely to have the disease and adopt aand adopt a WAIT-and-SEE WAIT-and-SEE policypolicy
By using techniques that offer a By using techniques that offer a high negativehigh negative predictive value predictive value i.e.i.e. a low false-negative rate a low false-negative rate
AMLAML
HSC transplantHSC transplant
Risk factor selectionRisk factor selection
Risk factors diagnosis
HSC transplantHSC transplant
febrilefebrile
RadiologyRadiology
MycologyMycology
febrilefebrile
PulmonaryPulmonaryInfiltrateInfiltrate
AntigenAntigen
++
Screening test for a potentially fatal disease Screening test for a potentially fatal disease with a low prevalencewith a low prevalence
+
-
Controls Tests
- -
+±
not ruled outnot ruled outstart treatmentstart treatment
not ruled outnot ruled outstart treatmentstart treatment
ruled outruled outwithhold treatmentwithhold treatment
ruled outruled outwithhold treatmentwithhold treatment
CT scanCT scan
At riskAt risk
3 x weekly GM-ELISA3 x weekly GM-ELISA
yes no
ELISA GM positive
OROROROR
> 5 d unexplained fever
OROROROR
abnormal chest X-ray
EORTC/MSG criteriaEORTC/MSG criteria
A strategy for managing pulmonary aspergillosisA strategy for managing pulmonary aspergillosis
therapytherapy wait-and-seewait-and-see
yesyes
yesyes
probable
no
unlikely
yesyesno
possible
Clinical features
Prevalence ≥ 10%
yesyes no
no
Microbiological evidence
A strategyA strategy
At riskAt risk
Pre-emptive therapyPre-emptive therapy
eg. CT scan halo-eg. CT scan halo-signsign
or air-crescent signor air-crescent sign
Obtaining a specimen - tools of the tradeObtaining a specimen - tools of the trade
BronchoscopyBronchoscopyBronchoscopyBronchoscopy
BrushBrush
BiopsyBiopsy
Bronchoalveolar Bronchoalveolar lavagelavage
Lung biopsyLung biopsyLung biopsyLung biopsy
Sputum Sputum Sputum Sputum
Fine needle aspirateFine needle aspirateFine needle aspirateFine needle aspirate
Bronchoscopy specimen - processingBronchoscopy specimen - processing
BALBALBALBAL Culture Culture Culture Culture
cytologycytologycytologycytology
CentrifugeCentrifuge500 g 5 min500 g 5 min
Martin et al 1987 Mayo Clin Proc 62:549-557
Aerobic bacteriaAerobic bacteria S. pneumoniae, Ps aeruginosaS. pneumoniae, Ps aeruginosaEnterobacteriaEnterobacteria KlesiellaKlesiella spp sppLegionellaLegionella spp sppMycobacteriaMycobacteria M. tuberculosisM. tuberculosisNocardiaNocardia spp sppMycoplasmaMycoplasma spp sppYeastsYeasts Candida Candida sppsppMouldsMoulds A. fumigatusA. fumigatusVirusVirus CMV, HSV, RSVCMV, HSV, RSV
GramGramGiemsaGiemsaSilverSilverAcid-fast stainAcid-fast stainIFAIFA --LegionellaLegionella
10-20 mL10-20 mL10-20 mL10-20 mL
10-20 mL10-20 mL10-20 mL10-20 mL CytospinCytospinCytospinCytospin
Shell vialShell vialcultureculture
Shell vialShell vialcultureculture
IFAIFA -CMV-CMV-HSV-HSV
-- RSVRSVinfluenza A & Binfluenza A & B
Mycology
Clinical features
Host factors + + ProbableProbable=
= Proven Proven Mycology
Clinical features
Host factors + +
tissue
Mycology+Host
factors
Negativeor
Not done
Clinical features+Host
factors
Negativeor
Not done=
=PossiblePossible
Invasive Fungal InfectionInvasive Fungal Infection
Conclusions Conclusions
• Patients at risk are better knownPatients at risk are better known
• The timing of the risk is better understood The timing of the risk is better understood
• Diagnosis is improvingDiagnosis is improving
• Criteria now exist for defining invasive mycosisCriteria now exist for defining invasive mycosis