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    FungiAssociatedwithRespiratoryTractInfections1

    NotesfromTheSeahorse

    ENDEMICRESPIRATORYMYCOSES

    Acquiredfrom Portalofentry PrimaryfocusofInfection Agents

    InhalationofCONIDIAfromsoil

    Conidia

    -Asexualspores

    - Notencloseinsac/sporangium

    Respiratorytract

    - Inhalationofconidia

    Noevidenceoftransmissionfromanimalstohumanorhumantohuman

    Lungs

    HaverestrictedgeographicdistributionExhibitTHERMALDIMORPHISM

    - Existasmold/myceliainenvironment

    - Yeastintissues/bodyCaninfecthealthyindividuals

    I.Histoplasmosis

    Characteristics Distribution Primarysourcesofinfection Occursas Causedby

    -AKADarlings/Cavers/Spelunkersdisease,NorthAmerican

    Histoplasmosis

    FirstdescribedbySamuelDarling

    Spelunker

    - Apersonwhosehobbyisexplorationandstudyofcaves

    NorthAmericanHistoplasmosisin

    contrasttoAfricanHistoplasmosishasa

    differentetiologicagent(Histoplasma

    duboicii)

    -Globallydistributed

    - Incidencevariesbutishighestin

    theUnitedStates

    o Soilo Bathabitatso AvianHabitats

    Turkeys,chickens,crows,blackbirds,starlingare

    associatedwiththeinfection

    Canbecontractedbyoccupationalexposure

    Spelunkers,batguano/droppingminers

    A.Asymptomaticinfection

    - 90-95%ofcases

    B.Pulmonaryinfection

    (acute/chronic)- 5-10%ofinfectedindividuals- Acuterespiratoryillnessor- Chronicformmimicstuberculosis

    C.Disseminatedinfection

    - Reticulo-Endothelialsysteminvolvement,mucocutaneous

    infection

    - FoundintracellularinREcells-Liverandspleenareaffected(hepatospleenomegaly)

    - Onchestx-ray,itmimicspulmonarytuberculosis(Lobar

    infiltrates)

    D.PrimaryCutaneousInfection

    - Veryrare- Cutaneousinfection

    usuallyofseenin

    disseminatedinfection

    Histoplasmacapsulatum

    - Misnomer,nocapsule- Ascomycete(ajellomyces

    capsulatus)- Thermallydimorphic:

    facultativeintracellular

    - Growsinsoilcontaminatedwithbird/batexcreta(soilhas

    highnitrogencontent)

    InfectiousParticle:MICROCONIDIA

    - hastobesmalltoreachthealveoli

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    FungiAssociatedwithRespiratoryTractInfections1

    NotesfromTheSeahorse

    LaboratoryDiagnosis

    HistopathSection CultureatRoomTemperature Cultureat37C IDofcultures Otherdiagnostictests

    Specimen:

    - bodyfluids- tissuebiopsies

    - StainedwithGiemsa/GMS/PAS

    - Small,roundtoovalintra-andextra-cellularyeastcells

    -OnGiemsaorWrightsstainedsmear:palebluebody(fungal

    cellwall)surroundsthedarker

    blueprotoplasma;cytoplasma

    retractsfromthewalls,giving

    thefasleimpressionofa

    capsule

    DIAGNOSTICMETHODOFCHOICE

    -moldisgrown

    Colonies:- Fineseptate,hyphae,largetuberculatemacroconidia and

    smallmicroconidia

    - Growmold

    Tuberculatemacroconidia

    - DiagnosticofH.Capsulatum

    - Cannotdistinguishthefunususingthe

    microconidia

    Microconidia

    -infectiousparticle

    **yeastisgrownhere

    Colonies:

    -Small,single-buddingyeastcells

    - StructuresseenaretheTISSUEFORM

    - Convertanddemonstratedimorphismtoconfirm

    diagnosis

    - CulturethefungusinBHI(Brainheartinfusion)

    - Incubateat37C- Moldphasewillconvertoyeastfaceandwillseethe

    buddingyeastcells

    - Laboratoryhazard- Microconidiacaninfect

    laboratoryworkers

    - Needtosetupfungal/mycology

    laboratorywithaBSC

    (BiologicalSafety

    Cabiney)workstation

    - Exoantigentest- Nucleicacidprobe

    *doneinlieuofmold-to-yeast

    conversion

    Skintest(histoplasmin)

    - NodiagnosticvalueSerology(CFtest)

    Complementfixationtest

    - Veryhelpful- HighCFantibodylevels

    meansapoorprognosis

    AntigenDetection(RIA,enzyme

    immunoassay)

    RIA-radioimmunoassayinvolves

    theseparationofaproteinfroma

    mixtureusingthespecificityof

    Ag-Abbindingandqunatation

    usingradioactivity

    TreatmentandPrevention

    Treatment Prevention

    Notrequiredformostcases-Mostcasesareasymptomaticandself-limiting

    Itraconazole,ketoconazole,fluconazole(pulmonary);amphotericinB(systemicordisseminatedforms)

    Surgicalresectionofpulmonarylesions

    - Wearingofprotectiveclothingbeforeenteringinfectedlabs- Soildecontaminationwith3-5%formalin(whenfeasible)

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    FungiAssociatedwithRespiratoryTractInfections1

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    BLASTOMYCOSIS

    Characteristics Occursas Causedby Infectiousparticle

    AKANorthAmericanblastomycosis,ChicagoDisease,

    GilchristsDisease

    FirstdescribedbyThomasGilchrist

    FoundinNorthAmerica,Africa,Asia

    Outbreaksassociatedwithactivities

    - Moistsoilenrichedwithorganicdebris,rottingwood- Prevalentwiththoselivingnearriversandstreams

    Naturaldiseasecommonincatsanddogs

    - Importantveterinaryproblem- Noanimal-humantransmission- Highprevalenceofcanineorfelineblastomycosisisa

    goodindicatorthatfungusispresentinarea

    OftenmisdiagnosedasTuberculosis

    A.Asymptomaticinfection

    - ~50%ofcases

    B.Pulmonaryinfection(acute/chronic)

    - Acutebronchopneumonialike- ChronicPTBlikeinchestxray;lungcavitationwithorwithoutlobarinfiltrates

    C.Disseminatedinfection

    - Skin,bonemostcommon- GUT,CNS,spleen,kidney

    D.ChronicCutaneousInfections

    - Indisseminativeforms- Verrucous/ulcerativelesions- Microabscessesareverycommonintheselesions

    E.PrimaryCutaneousInfection

    -rare

    Blastomycesdermatitidis

    -Ascomycete(Ajellomycesdermatitidis)

    -Nameinparenthesis=sexualstate

    -Thermallydimorphic-Inhabitsdecayingwoodandmaterials;probablysoilsaprophyte

    -Veryrarelyculturedformsoilinendemicareas

    Conidia

    -nomicro-or

    macro-conidia

    LaboratoryDiagnosisKOH/histopathexams CultureatRoom

    Temperature

    Cultureat37C IDofcultures Otherdiagnostictests

    Specimen:

    - dependonmanifestations;skinscrapings,pusfromskinlesions,sputumsinpulmonarydiseaseorbiopsytissues

    - - Showsthick-walledyeastcellswithsinglebroadbasedbud

    - characteristicofBlastomycesdermatidisisthebudattachedtoparentcellbybroadbasew/cisdifferentfromotheryeastcells

    w/careattachedbyanarrowbase

    Pyriformconidiaborne

    singleonseptatehyphae

    -nocharacteristic

    patternofconidiation

    -Double-walledyeastcellswithsinglebroad-

    basedbud

    -Seeneveninvitro-Brainheartinfusion

    -Exoantigenttest-Nucleicacidprobe**Bothdoneinlieuof

    moldtoyeasttest

    SkinTest(blastomycin)

    -Nodiagnosticvalue

    Serology(CF,

    Immunodiffusion)

    -Complementfixation-Tissueidentification

    Immunofluorescence

    Antigendetection(RIA)

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    FungiAssociatedwithRespiratoryTractInfections1

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    Treatment:

    Pulmonary CutaneousManifestations Disseminated

    Ketoconazole

    Itraconazole

    Flucanozole

    Excision/correctivesurgery AmphotericinB

    COCCIDIOIDOMYCOSIS

    Characteristics OccursAs: Causedby Infectiousparticle Tissueform

    AKAPosadasDisease,San

    JoaquinVallefever,Desert

    rheumatism

    FirstdescribedbyAlejandro

    Posadas

    EndemicinWesternHemisphere

    Highestepidemicity:Semi-arid

    regionswithalkalinesoils

    (Sonorandesert)

    Outbreaksoccurfollowingdust

    storms,earthquakes,evacuations

    thatspreadtheinfectiousparticle

    A.AsymptomaticInfections

    - ~60%ofcases

    B.PulmonaryInfections

    - ~38-40%ofcases- Acuteorchronic- Acute:mild,chestpain,

    cough

    - Chronic:

    C.DisseminatedInfection

    -

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    FungiAssociatedwithRespiratoryTractInfections1

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    Laboratorydiagnosis:

    Specimen:Sputum,pusfromskinlesions,aspirates,CSF,andskinbiopsy

    KOH/HistopathExam CultureatRoomTemperature Cultureat37C IDofCulture OtherDiagnosticTests

    -thickwalledspherulesfilled

    withnonbuddingendospores

    Hyphaebearingbarrel-shapedarthroconidiaseparatedbydysjunctorcells

    Dysjunctorcells

    - pointsofdisarticulation- Hyphaewithemptyspaces

    NotroutinelydoneMoldtoyeastconversionverydifficult

    Exoantigentest Nucleicacidprobe Demonstrationofspheruleproductioninanimals

    Skintest(coccioidin/spherulin)

    -Quiteusefulincoccidioidomycosis

    Serology(CF,Immunodiffusion)

    -Associatedwithhighcomplementfixationantibodytiter=Poorprognosis

    Immunofluorescence

    -toconfirmdiagnosis

    Treatment Prevention

    Acuterespiratorydisease

    - Notnecessarytotreat

    ForPulmonaryandDisseminatedDisease:

    - Itraconazole- Ketoconazole- Fluconazole(formeningitis)- AmphotericinB(disseminated)

    Surgery

    Reduceexposuretodust(soil)inendemicareas

    Vaccinedevelopmentinprogress

    Brieftraveltoendemicareacanleadtoinfection Veryinfectious

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    FungiAssociatedwithRespiratoryTractInfections1

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    PARACOCCIDIOIDOMYCOSISCHARACTERISTICS OCCURSAS CAUSEDBY INFECTIOUSPARTICLE

    AKASouthAmericanblastomycosis,

    BrazilianBlastomycosis,LutzSplendore-

    AlmeidasDisease

    HigherincidenceinMALES(9-15:1)

    - Myceliumtoyeastconversionsinhibitedbyestrogen

    EndemicinCentralandSouthAmerica,

    SouthernMexico

    AsymptomaticInfection

    Pulmonaryinfection

    - Acuteflu-likeorpneumonialike- Chronicmimic

    coccidioidomycosisorPTB

    DisseminatedInfection

    - Granulomatouslesionsinoralandnasalmucosa (mulberry

    lesions)mostcommonand

    characteristicof

    paracoccidioidomycosis

    - Cellwallpolysaccharide(alpha-glucan)stimulatesgranulomaformation

    Paracoccidioidesbraziliensis

    - Deuteromycete- Thermallydimorphic- Naturalhabitatisunknown- Foundtoresideinhumidsoilrich

    inproteins

    - Rarelyrecoveredfromendemicareas;hasbeencultivatedinfruit

    batsandarmadillos

    CONIDIA

    Laboratorydiagnosis

    Specimen:sputum,biopsymaterials,pusandcrustsfromlesions

    KOH/HISTOPATHEXAM CultureatRoomTemperature Cultureat37C IDofcultures Otherdiagnosittest

    - yeastcellswithmultiplenarrow-basedbuds

    Septatehyphaewithnotypical

    patternofsporulation

    YeastcellswithMariners/

    steeringwheelappearance

    - Characteristicfeature

    ExoantigentestDNAprobe

    Skintest(paracoccidioidin)

    - Stillofnotmuchuse

    Serology

    - CF- Immunodiffusion(betterchoicethanCF)

    Treatment

    Ketoconazole,itraconazole,sulfadrugs,AmphotericinB

    - MoreofamphotericinBsincemostofthesearesystemicinfections

    SurgicalExcisionoflocalizedlesions

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    FungiAssociatedwithRespiratoryTractInfections1

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    PENICILLIOSISMARNEFFEI

    CHARACTERISTICS OCCURSAS CAUSEDBY RESERVOIROFINFECTION HABITAT INFECTIOUSPARTICLES

    EndemicinSOUTHEAST

    ASIA

    (Thailand,China,Hong

    Kong,Vietnam,Indonesia,

    Taiwan,India)

    Naturallyoccurinfections

    havebeenfoundin

    bamboorats

    Becomeanearlyindicator

    ofHIVinfectioninendemic

    areas

    - EspeciallyThailandwhereHIVprevalenceishigh-Notconsideredopportunisticbecauseit

    infectsboth

    immunocompetentand

    immunocompromised

    patients

    PulmonaryInfection

    -Acuteorchronic-Singlelesiontomilliaryspread

    DisseminatedInfection

    - SimilartodisseminatedHistoplasmosis(RES

    INVOLVEMENT)

    ThereisNOasymptomatic

    infection

    ChestX-Ray

    -Mimicanylesionsinthelungs/infiltrates

    -Singleormiliary

    Penicilliummarneffei

    -onlyspeciesofpenicillium

    thatisTHERMALLY

    DIMORPHIC

    - ReproducesbySCHIZOGONY

    (TRANSVERSEFISSION)

    o Notthroughasexualprocessof

    budding

    o Hasmoldandyeast

    o Dividesintotwo

    BambooRats

    Unknown

    Conidia

    LaboratoryDiagnosisandTreatment

    Specimen:blood,bonemarrow,urine,stool,CSF,skinandvariousinternalorgans

    KOH/HistopathExam Cultureatroomtemperature Cultureat37C IDofCultures Treatment

    Small,yeastcellswith

    transverseseptum(dueto

    transversefission)

    -dividesequallyintotwo

    Conidiophores branchinto

    metullaewhichsupportthe

    phialidesthatbearchainsof

    conidia(calledthePENICILLOUS

    STRUCTURE[PAINTBRUSHLIKE]

    Coloniesproducediffusiblered

    pigment

    -uniquecharacteristic

    Roundtoovalyeastcellswith

    cross-walls

    o Exoantigentesto Conversiontoyeastform

    Itrconazole,ketoconazole

    AmphotericinB

    -seriouslyillordisseminated

    infections