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SYSTEMICMYCOSESSYSTEMICMYCOSESLiaoAcademicianofChineseEngineeringAcademyChiefofShanghaiKeyLaboratoryofMolecularMycologyChiefofDermatologyandMycosisInstitute,Changzheng•mycosesareendemicin•mycosesareendemicingeographicareas,whichcanoccurinbothimmunocompormisedandimmunocompetenthoststhroughinhalationordamagedmucosaandskin.•TheseimportedinfectionswererareinChina,butisontheriseduetoincreasedinternationalAndit’salarmingthatsomeimportedmycosescaseswerealsoreportedin组织胞浆菌组织胞浆菌病球孢子菌病副球孢子菌病芽生菌病•Thesefourfungiusuallyexistinparticularenvironment,associatedwithspecialclimate,earth,animals•Thesefourfungiusuallyexistinparticularenvironment,associatedwithspecialclimate,earth,animalsorplants,whichmaycontributetoitsgeographicdistribution.Withincreasedinternationalcommunications,however,thereisanincreasingtrendinimportedcasesofabovefourmycoses(mainlyrespiratorySimilarclinicalmanifestationinpatientswiththesemycoses.••NorthSouthNorthSouthDermatologyinDermatologyingeneralmedicine-ThomasBernardPathogens:HistoplasmaPathogens:Histoplasma-H.capsulatumvar.capsulatum,globallydistributedbutmainlyinNorthAmerica.-Hcapsulatumvar.duboisii,mainlyinFungikingdom,Feuteromycotinasubphylum,Haplomycetesclass,Monilialesorder,Moniliaceaefamily.Dimorphicfungus:sexualstage,AjellomycesInfectionchannels:inhalation,mucocutaneouscontact,andgastrointestinalintack.••••95%ofprimaryinfectionwithoutanysymptoms,butdisseminatedHistoplasmosis95%ofprimaryinfectionwithoutanysymptoms,butdisseminatedHistoplasmosisoccurringinimmunocomprisedptssuchasHIVinfection,receivinglong-termcorticosteroidsorotherimmunosuppresantstreatment.HistoplasmosisrarelyoccuresinAsia,andmostcaseswereimportedinfections.InChina,Histoplasmosiscasesweremostlydiagnosedthroughtissuebiopsyonly,andtheywerehardtobedifferentiatedfromPenicilliummarneffeiinfectionand•••TheinfectionTheinfectionsourcesareavianspeciessuchaschicken,bat,pigeon,andtheircontaminatedsoil.Chickencoop,birdnest,caveswithbatgatheringandmoistearthcanbehighlycontaminatedbyH.capsulatum,andthusbecomethemainsource.Manypatientswithimportedinfectionhadcleardescriptionoftravellinghistory.Histoplasmosisisepidemicintemperatezone(30Histoplasmosisisepidemicintemperatezone(30℃S,45℃N).ItwasoncereportedinUSA,Mexico,Africa,Austrilia,Turkey,Indonesia,Philippines,etc.Over80%adultsintheMississippiRiverValleywereinfectedwithImportedinfectionsinJapanImportedinfectionsinJapanoncereportedthreepatientsinfectedThesethreehealthywomentravelledLangkawiinMalaysiaforabout5returning,theyallmanifestedflu-likesymptomsandwerefinallydiagnosedaspulmonaryHistoplasmosis.ClinicaldoctorsshouldbewareofitsoccurrenceinChina,consideringincreasingoutboundtourism.ThefirstThefirstHistoplamosiscaseinChinawasreportedin1955,whichoccurredinareturnedoverseasChinesefromSingapore.Duringthefollowing50years,about100caseswerereportedinChina,mostofwhichweresporadicandwithmalepredominance.2006DisseminatedHistoplasmosis,Guiyang(JiafengLi)2007DisseminatedHistoplasmosis,Taiwan(Hsi-HsunLin)2008DisseminatedHistoplasmosis,Hebei(DongyanShi)2009DisseminatedHistoplasmosis,Chengdu(YuKuang)2010CavitaryMucousHistoplasmosis,Chengdu(FeiHao)Allcaseswerediagnosedbyculturetestand/ormolecularbiological••SporadiccasesSporadiccasesin•11patientswithHistoplasmosisdiagnosedculturetestinHubeihadnooutboundtravelhistory,andlivedinYangtzeRiverValley.HisplasmosiswasendemicintemperateChinaisalsosituatedtemperatezone,HisplasmosiswasendemicintemperateChinaisalsosituatedtemperatezone,thustheincidenceofHistoplasmosiswouldnotbelowInspiteofsporadiccasesreportedinChina,positiveratesofhistoplasminskintestwerequitehigh,whichconfirmedthatlotsofpatientshadapreviousinfectionofHistoplasmosis.PositiveratesofhistoplasminskinThereisasignificantstatisticaldifferenceinpositiveratesofhistoplasminskintestcomparingNanjingwithShaoyangorChengdu(P<0.01),butnostatisticaldifferencebetweenShaoyangandChengdu(P>0.05).Eshengwu,yidaosun,beileizhao,suqiuliu.Investigationontheepidemiologyofhistoplasmcapsulatuminfectionincentralsouth(shaoyang),eastofchina(nanjing)andwesternsouth(chengdo).NormalPtswithSouthEastSouthwestMianzhuCountyinMianzhuCountyinChengduisabundanceofrainfalland50%ofpatientshasahistoryofchicken,pigeonorbatShaoyangishumidandwarm,andabout90%ofpatientshassimilarexposurehistory.NanjingissituatedinPlainregion,andwithhighereconomicallevel.Thereismuchfewerofsimilarexposurehistoryinlocalresidents.Anotherhistoplasminskintestshoweda2.1%positivityin93healthymalesinUrumuqi.AllthedataaboveconfirmedthathumidenvironmentandhostanimalsmaybeimportantsourcesofH.capsulatum.•••••FirstdiscoverythatHistoplasmosiswasdistributedFirstdiscoverythatHistoplasmosiswasdistributedinYangtzeRiverValleyinChina.28ymale,chroniccourse,fromHunanComplaintofabdominalpainaccompaniedwithhepatosplenomegalyfor7months,andfeverfor3PancytopeniainBloodroutinePASposotivebodiesinsidesplenicsinusinTissueMacrophagescontainingpathogensinmarrowpunctureexamination,Penicilliummarneffei?orH.capsulatum?FirstdiscoverythatHistoplasmosiswasdistributedinYangtzeRiverValleyFirstdiscoverythatHistoplasmosiswasdistributedinYangtzeRiverValleyinChina.Tissuecultureofsuperficiallymphnodedisplayedfilamentousfungusaftermorethan14daysincubationat30℃.ThefunguswasidentifiedasH.capsulatum(Ajellomycescapsulatus)throughITSsequencetestandMsp1/2amplificationinourlab.PCRMicroscopicCulturePathogenchangesofPathogenchangesofinvasivefungalFirstdiscoverythatHistoplasmosiswasdistributedinYangtzeRiverValleyinChina.TheHisplasmosispatientcomefromHunanProvince.Afterliteraturesearch,300caseswerereportedinChina,whichdisplayedaprominentgeographicaldistributionandmostwithoutoutboundtravelHistoplasmosis:anewendemicfungalinfectioninChina?Reviewandanalysisofcases.Mycoses.2012Dec10.doi:10.1111/myc.12029.★Biological★wasthoughttobeimportedinChina ★Biological★wasthoughttobeimportedinChina ClinInfectDis.2013.56.Mycoses.2013.EnvironmentinvestigationincaveDatainYunnanCulture,animalinoculation,nestedPCR,sequencewereusedtoisolatetheEnvironmentHistoplasmacapsulatumHistoplasmacapsulatumcausesinfectionmainlyviainhalation,whichcouldsurviveandpropagateinpulmonaryalveolarmacrophages.CD4+andCD8Tcellsplayimportantrolesinpathogenclearance.Transmittootherorgansthroughlymphaticducts,lymphnodesandblood.Inimmunocompetentpatients,granulomaisformedandoccasionallycaseousnecrosisoccures.Granulomacouldbefollowedbyfibrosisandcalcificationinimmunocompetentpatients.Itneedstobedifferentiatedfromtuberculosis.Autoimmunereactiontoitsantigencouldcausearthritis,pericarditisanderythemanodosum.Inimmunocomprisedpatients,H.capsulatumcouldcausedisseminated•••••••InfectionmainlyInfectionmainlyinpatientsoranimalfecesinEndemicareas.CanyouCanyoufindouttheH.cellsintheClinicalClinicalmanifestationClinicalClinicalmanifestationdependsonimmunestatusandexposureextent.Histoplasmosiswasclassifiedintopulmonaryanddisseminatedinfection.••PulmonaryPulmonaryWhenexposedtolow-inoculumH.capsulatuma,about90%patientshadnosymptoms.High-inoculumexposurecouldcauseacuteself-limitedpulmonaryHistoplasmosiswithflu-likesymptomsincludingdrycough,chestpain,breathshortness,hoarsenessetc.Chestradiographshowedanenlargedhilar/mediastinallymphnodesorpatchypneumonia. SeverecasesmanifestedasARDS,arthritis,erythemanodosum,andpericarditis.Calcificationlesionwasleftafterresolvement.RapidProgressivePulmonaryHistoplasmosismostlyoccuredinimmunesuppressedpatientsandshowedchroniccavitaryformation.Afewpatientscouldrecoverwithouttreatmentwhilemostdevelopedaschronicinfectionandevencausedisseminatedhistoplasmosis.Disseminated••UsuallyDisseminated••UsuallyoccursinchildrenorimmunesuppressedChronicdisseminatedHistoplasmosis:weightloss,fatigue,andfever(1/3pts).SubacutedisseminatedHistoplasmosis:fever,weightloss,fatigueaccompaniedbyoralulcerandhepatosplenomegaly.Pancytopeniawasshowninsomepatients.Otherorganssuchasadrenalgland,aorta,mitralvalveandCNScouldbealsoinvolved.Withouttreatment,patientswoulddiewithin24months.AcutedisseminatedHistoplasmosis:fever,pulmonaryinfiltrates,andsepticemia.Besides,somepatientswithdisseminatedHistoplasmosismayshowatypicalsymptomslikegastrointestinalulcers,bleeding,skindamage,adrenalinsufficiency,meningitisand•••H.Capsulatumvar.H.Capsulatumvar.Histoplasmacapsulatumvar.duboisiimainlyinfectedcouldinvadeskin,subcutaneoustissueandCommonsymptoms,suchaschroniculcersandsubcutaneousnodules.Osteoarticularinvolvement,osteolyticlesionsandthenchronicNosignificantcorrelationwithpatients'immunestatus.H.capsulatumvar.ComparedH.capsulatumvar.ComparedtoH.capsulatumvar.capsulatum,H.var.duboisiicellislargeandbreakdownurea.thick-walled,andcanInhosttissuethemophologyofH.capsulatumvar.duboisiiwassimilartothatofButformershowedanarrowneckwhenbudding,anditsdaughtercellcouldgrowtosimilarsizewithoutseperatinglikeapairofGoldenstandardindiagnosis:culturetestsGoldenstandardindiagnosis:culturetestsoftissueorbodyColonycharacteristicsappearedafter2-3weeksincubation,duetoitsslowgrowth.•••W-GstaintestcellularH.capsulatuminblood,bonemarrowsmear,andalsobiopsyH.capsulatumtransfersfromhyphalstagetoyeastformatAtransparenthalosimilartocapsulewasshownaroundcellwallinHEstain,butnotinPASEasytocauselab•••ColonialThickwallColonialThickwallgear-shapeconidiainfilamentouscolonyisofsignificanceforcorrectdiagnosis.H.capsulatumdisplayeddifferentcolonialmorphologywhenincubatedonvariousmediumoratdifferenttemperature(25℃Vs37℃)PathologicIntracellularyeast-likestrainsinsputum,blood,bonemarrowsmear,orlymphnodesspecimenareindicativeofhistoplasmosis.However,it’snecessarytobefromPenicilliosismarneffeiiCottonycolonyCottonycolonysimilartoParacoccidioidesonSabouraudConidiosporesofH.ConidiosporesofH.capsulatuminmycelialColonyinmycelialphase：slenderseptatemycelia,roundorpyriformmicroconidiawith2-3umdiameter,thick-wallandgear-shapemacroconidiawith8-15umW-GstainW-GstaininbonemarrowintracellularH.capsulatumwith3-5umGMSstainGMSstainofpulmonarytissuedisplayedH.capsulatuminsideHistoplasmacapsulatumHistoplasmacapsulatumvar.duboisiicellsafterGMSPASstainPASstainofH.casulatuminliverH-EW-GH-EW-GPulmonarybiopsyspecimenwithmultiplewhitenodules;LotsPulmonarybiopsyspecimenwithmultiplewhitenodules;Lotsofyeast-likecellsintissuesectionafterGSMstain.AntigenH.capsulatumpolysaccharideAntigenH.capsulatumpolysaccharideantigencouldbedetectedinurineandserum.Sensitivityandspecificityfordisseminatedwere90%and80%,SensitivityofAntigendetectionwashigherinurinethanthatinserum.ThetiterofHistoplasmaantigencouldbeusedtoevaluatetheefficacyandandmonitortherecurrence.••••Cross-reactionwasalsoshowninBlastomycetesand•LabSkinantigentest:notavailablefordiagnosis;PositiveresultoftenLabSkinantigentest:notavailablefordiagnosis;Positiveresultoftenindicatespreviousinfection,whilenegativeresultcannotexcludeacutedisseminatedinfection.Antibodytest:fewapplicationvalueduetoitslate-onsetpositiveresults(4-8wksafterinitialsymptoms)anditsunavoidablecross-reaction.Immunodiffusionmethod(H-Mzone)Molecularbiologicaltest.••••DifferentialPenicilliumDifferentialPenicilliumEndemicinSoutheastAsiaandSouthChina,mostlyinfectedimmunocompromisedpatients.Dimorphicfunguswithrapidgrowth,fluffycolonyandroseCharacteristicmicroscopicstructuresuchaspenicilliandsporangia;ReproductionbyAmphotericinB.Penicilliummarneffi,sausage-Penicilliummarneffi,sausage-cells（PASPenicilliummarneffi:shapedcells（PAS临床病例实际分临床病例实际分1、青年患者，反复腹痛、腹泻2年余患者，男，27岁，水电工，已婚，育有3个子女肠镜检病理可见：回盲部重度慢性炎症累及粘膜下层见多发性非干酪死性上皮样肉芽肿（含多核巨细胞，以朗罕氏巨细胞为主）外院按“炎症性肠病”、“肠结核”治疗2年后无好转血常规：WBC3.71X109血常规：WBC3.71X109/L，RGB1.90X10^12/LHb46g/L，N%48.8%L，PLt195X10^9/L复习肠组织病理，行PAS复习肠组织病理，行PAS痰培养血培养penicillium痰培养血培养penicilliummarneiffeiwasalsoidentifiedbyITSsequenceCandida“HistoplasmosiscausedbyH.capsulatumisquitesimilartovisceralleishmaniasisinclinical“HistoplasmosiscausedbyH.capsulatumisquitesimilartovisceralleishmaniasisinclinicalsymptoms,andfurthermorethepathogensseeninlymphnode,bonemarrowandspleenwouldbemistakenasDonovan.”---Wang•EndemicinTropicalAmerica,XinjiangandInnerMongoliaprovincesofChina.Clinicalmanifestations:long-termirregularfever,splenomegaly,pancytopeniaandbleeding.Cellularinclusion-bodywithuniformsize,andalsowithkinetoplast,andsausage-shapedcells.Culturetest:nogrowthonfungalculturemedium.Treatment:••••AmphotericinBwasAmphotericinBwasusedtotreatsevereHistoplasmosisordisseminatedHistoplasmosisItraconazolewasusedasfirst-lineoralagentforpatientswithmildtomoderateHistoplasmosis.Fluconazole,Voriconazoleandposaconazolecanbeusedasalternativedrugs.Echinocandinsshouldnotbeusedfor••••IDSAmodifiedIDSAmodifiedthetreatmentguidelineforHistoplasmosisinMostpatientswithmildHistoplasmosiscanrecoverwithouttreatmentandasymptomicpatientsdon'tneedtreatment.Therefore,itshouldbeverifiedwhetherantifungaltreatmentisnecessary.RecommendedtreatmentforsevereacutepulmonaryHistoplasmosis.LipidformulationofamphotericinB(3.0–5.0mg/kgdailyintravenouslyfor1–2weeks)followedbyitraconazole(200mg3timesdailyfor3daysandthen200mgtwicedaily,foratotalof12weeks)isrecommended(A-III).Prednisone(0.5–1.0mg/kgdailyisrecommendedforpatientswithevidenceofhemodynamiccompromiseorun-remittingsymptomsafterseveraldaysoftherapywithnon-steroidalanti-inflammatorytherapy.Patientscanrecoverrapidlywithinoneweekafterbeing-ClinInfectDis.2007;45(7):807-Alternative•AmphotericinBdeoxycholateAlternative•AmphotericinBdeoxycholate(0.7–1.0mg/kg/day).LipidformulationofAmBshowedbetterefficacyandlowermortalityaccordingtoRCTresearch.Fluconazolecanbeusedinpatientsintolerant•theformerislesseffective,andrisksofdrugPosaconazoleandvoriconazoleweresucceededintreatinginfectionofrareorgans(suchasHistoplasmosisabscessinconusmedullaris)andalsoinrescuetherapy.ButthereisnoRCT•HistoplasmosiscapsulatumantigendetectionHistoplasmosiscapsulatumantigendetectioncanbeusedtopredicttheprognosis.••Fibrousmediastinitisdisplayedbutpoorprognosis.slow•Followingfactorswerealwaysindicativeofpoorprognosis,suchashemoglobincount<80g/L,AST2.5timeshigherthannormalvalue,acuterenalfailure,respiratoryfailure,thrombopenia,andalsoLDHtwicehigherthannormalvalue.LocalizedordisseminatedinvasiveLocalizedordisseminatedinvasivemycosiscausedbycoccidioidesimmitisorCoccidioidesPosadasii.FirstcasewasreportedbyPosadasandWernickein1892.In1894,RixfordfoundhundredsofcaseinCalifornia,USA.Endemicdiseasewithstronginfectivitybutspontaneoushealing.•••FirstcaseCoccidioidomycosis(tongueinChinawasreportedinTianjinin1958.patientwasreturnedoverseasChinesefromPathogen:CoccidioidesPathogen:CoccidioidesimmitisandCoccidioidesC.immitis:EndemicinCalifornia,C.Posadasii:EndemicinotherareasoutsideCalifornia,USA.Coccidioidomycosiscausedbyabovepathogens,showssimilarclinicalmanifestations.ThusbothtwospecieswerecalledCoccidioidesimmitis••CoccidioidesDimorphicHumaninfectioniscausedbyinhaledarthroconidia,whichreachthelowerrespiratorytractandconverttoCoccidioidesDimorphicHumaninfectioniscausedbyinhaledarthroconidia,whichreachthelowerrespiratorytractandconverttoitstissuephasespherules.Spherulesincreaseinsizeandproducehundredsofendospores,whicharesubsequentlyreleasedintothetissueandformnewspherulesfornewlifecycle.Coccidioidescellsgrowasbranchingseptate••••inLifecycleofCoccidioidesAgreatnumberofendosporesinathick-walledfungalCoccidioidesAgreatnumberofendosporesinathick-walledfungalcellbyH-Estain.EndosporesreleasedfromspheroidcellbyGSMDistributionmainlyDistributionmainlyinsouthwesternUnitedStates,NorthernMexico,andSouthAmerica.Ecologicalniche:dry,hotandsalt-alkalinizedsoil(desert);rodent;Cacti.••NorthSouthNorthSouthIt’sIt’sestimatedthat150,000newcasesofoccurseachyearinDryweatherafterrainfallinendemicareascouldleadtohumaninfectionbecauserainfallwasbeneficialforitsgrowthinthesoilandfollowingdrywhethercontributedtoarthrosporeaerosolizationintheair.During1980sand1990s,anoutbreakofCoccidioidomycosisoccurredinCaliforniaduetoincreaseofHIVpatientsandfavorableclimatethere.Duststorm,earthquakeanddroughtdisastercouldalsocontributetoitsoutbreak.Filipino-AmericanandAfrica-AmericanpatientswasmoresusceptibletodisseminatedCoccidioidomycosiswitha10to175timeshigherrisk.Accordingtoitsetiologicalniches,onlywestInnerMongolia,NorthGansuandAccordingtoitsetiologicalniches,onlywestInnerMongolia,NorthGansuandsouthXinjiangaresuitableforgrowthofCoccidioidesimmitis.Butrelatedepidemiologicaldataislack.AfewCasesreportedin••19631985199820082009球孢子菌病2培养证实病理诊断-A43years-olddockworkerinHongkongwasreportedtobeinfectedwithCoccidioidesimmitisA43years-olddockworkerinHongkongwasreportedtobeinfectedwithCoccidioidesimmitisthroughcontactwithshipmentcargoesfrom-NEnglJMed(2011),TwocaseswithpulmonaryCoccidioidomycosiswasreportedinHongkong,bothofwhomhadaoutboundtravelhistoryinendemicareasofUSA.-Respirology(2008)14,InfectionviaInfectionviaStrongvirulence:pulmonaryinfectioncouldbecausedbysinglearthrospore,whichcouldformspherulescontaining••lotsofreleasedhundredsendosporesandthenformnewTcell-mediatedimmuneresponseplaysanvitalroleincontrollingitsdevelopment.•ClinicalMostpatients(60%)withoutClinicalMostpatients(60%)withoutanyAbout40%patientswithflu-likesymptomssuchas••cough,fever,dyspnea,chestpain,weightheadache,orerythemanodosum. Thosepatientscouldrecoverwithouttreatment.About5%asymptomicpatientswithpulmonarycavityandnodule.(PrimarypulmonaryCoccidioidesimmitis)Chronicprogressivepulmonaryinfectionmayoccurinimmunocompromisedpatients,withgrowingthin-walledcavitycombinedwithbronchopleuralfistulaor••ClinicalAboutoneof200patientswithCoccidioidomycosisClinicalAboutoneof200patientswithCoccidioidomycosisdisplaysextrapulmonarysystematicinfectioninvolvingskin,softtissue,skeletalsystem,andmeninges.Commonsymptomsinskininfectionwerepolymorphicpapulesandplaque.Fistulaandulcerwerecommonininfectionbyinoculation.BoneLesionwascharacterizedbyosteolysis,andmostlyinvertebrae. damagemostlyoccurredinankleandknee.Coccidioidomycosisfungemiawasfateful,whichcommonlyoccurredinimmune-compromisedpatients.Megingealinvolvementusuallyoccurredinthebasalpartofmeningiomas.Withouttreatment,about90%patientswoulddiewithinoneyear.LabCoccidioidesLabCoccidioidesimmitisintissueandbodyfluidsexaminedbymicroscopyhasdiagnosticimportance.Roundthick-walledspherulewithlotsofendosporesisitscharacteristicRapidgrowthonSabouraud‘sdextroseagar.film-likecoloniesclingedtothemediumwereshown3to4days.Andthenturnintocotton-likefollowedbylightbrownandpowder-likeones.Arthrosporeandchlamydosporecanbeshownthen.•SpheroidcellsSpheroidcellswithendosporesinhistopathologyH-Estain.HistopathologytestHistopathologytestofmousemodelpulmonarycoccidioidomycosis(H-ELabSerologicaltestissensitiveby90%,buttheantibodycannotLabSerologicaltestissensitiveby90%,buttheantibodycannotbeproduceduntil3monthsafteracuteinfection.IgMispresentsoon,butitstiterreducesafterwards,whichcanreflecttheprogressionratherthantheseverityofCoccidioidomycosis.Morethan1:16ofIgMtiterissuggestiveofdisseminatedinfection.DNAprobeforCoccidioidesimmitisiscommerciallyavailableandtheresultcanbeobtainedwithinhours.•••TreatmentGuidelinesforTreatmentGuidelinesforCoccidioidomycosisin•TreatmentforPrimaryRespiratoryInfection,orasymptomaticpulmonarycavityornodulesdonotrequireintervention.Butwhenpulmonarycavityisaccompaniedwithcombinationsofpyothoraxandbleeding,itshouldberesectedandoralazoleshouldbeused.Thosewithprogressivecocci-dioidalinfectionsshouldbegivenAmphotericinB0.5-0.7mg/kg/dforseveralweeksandthenreplacethemwithAzoleantifungalsforoneyear(itroconazole200mgbid,Fluconazole400-800mg/d).immunosuppressedpatientsshoulduseazoleantifungalsincaseofreplase.•-ClinInfectDis.2005;41(9):1217-•Extrapulmonary•ExtrapulmonarynonmeningealCoccidioidomycosiscanbetreatedwithoralitroconazoleorfluconazole.AmphotericinBisrecommendedforalternativetherapy,especiallyiflesionsareappearingtoworsenrapidlyandareinparticularlycriticallocations,suchasthevertebralCNSCoccidioidomycosisshouldbetreatedwithazolesforthelifetime(e.g.fluconazole800mg/d).someclinicalcasesreportthatfluconazolesuccedintreatingthisdisease.•Consideringits•Consideringitsstronginfectivity,vaccinedevelopmentisanewspot.•Currently,nowell-madevaccineonthePathogen:DimorphicfungusParacoccidioidesbrasiliensis,distributedinPathogen:DimorphicfungusParacoccidioidesbrasiliensis,distributedinLatinAmericaandmainlyendemicinBrazilandSkintestsdisplayedequalprevalenceinbothmaleandfemale;Systemicinfectionswerecommonlyinmalemorethan30IsolatedcasereportswereoncedescribedinUSA,Canada,EuropeandAsia.Butallwereimportedinfection.NocaseshaveeverbeenreportedinChina,whichmightbeduetofewtravellerstoSouthAmerica.••••Etiologicalniche:Etiologicalniche:Tropicalforestwithheavyrainfall,shortwinterandhumidSummer.AmazonRainforestinLatinAmericaisagoodnaturalnichesforParacoccidioidesbrasiliensis.•brasiliensiscasesoutside•brasiliensiscasesoutsideLatinAmericawereimported.•EndemicinSouthAmericacountries,suchasBrazil,Columbia,Nigaragua,andGary.Imported•Japanreported17Imported•Japanreported17casessince1960s.15ofthemhadevertravelledtoBrazil,andtheothertwooncewenttoParaguayandBolivia.Allimportedinfectionpatientshadeverlivedinendemicareasforyears.ThisisquitedifferentfromhistoplasmosisandCoccidioidesimmitiswhichhadashort-timeJInfectChemother(2003)••Withincreasinginternationalexchange,theriskofimportedinfectionofParacoccidioidesbrasiliensisisontheClinical••InfectionClinical••Infectionroutes:inhalationorskinMostinfectionswereself-limited,andonlywithpositiveresultsinskintest.Latentinfectioninvivoforalongtime,andthenattackwhenimmunocompromised.Patientsinfectedbyinhalationmanifestedaspulmonarysymptomssuchaspersistentcough,purulentsputum,chestpain,fever,andsoon.••ClinicalClinicalPulmonarylesions:nodules,infiltrates,fibrosisorcavity.Extrapulmonarymanifestationswouldbepresentindisseminatedinfectionwithoutefficientcontrol.Skinlesions:verrucousproliferation,ulcer,orgranuloma;commoninoralcavity,noseorlowerlimbs.Painfulmucosaulcerinvolvedinlips,gum,toughandClinicalAbdominalClinicalAbdominalsymptomsiscommon,includingdiarrhea,jaundice,asciticfluid,andintestinalobstruction.••CNSinvolvementin10-25%patients,manifestsasconvulsion,hemiplegia,headache,cerebraledemaandparesthesia.CSFroutineexaminationisusuallynegative.ButGp43antigenorantibodyhashighsensitivityandLabParacoccidioidesLabParacoccidioidesbrasiliensisdiscoveredinsputum,BALF,pus,CSF,ulcersecretionorbiopsyspecimenisofsignificanceforcorrectdiagnosis.Characteristicfeature:multilateralbuddingsporewiththeshapeofsteeringwheel.••Lab•SlowgrowthSabouraudLab•SlowgrowthSabouraudagar;whiteoraerialhyphaeandmicroscopy;yeast-likecolonywithgyrus-surfaceatOntheLab•Hispathology:Lab•Hispathology:pyogenicgranulomasimilartoB.dermatitidis,infiltrationofpolymorphonucleargranulocytesandintracellularspores.giantcellsLabAntibodytestLabAntibodytestcanbeusedfordiagnosisandefficacyevaluation.••Antigendetectioninserumandurineisalsohelpfulfordiagnosis.•MolecularBiologyItroconazoleissuitableforItroconazoleissuitableforbothadultsandchildrenpatients(100mg/dfor6months).••PatientswithrecurrentorsevereinfectioncanbetreatedwithAmphotericinB(accumulateddosageof1.2-3g)thenSulfanilamideazolesformaintenanceDermatitisPathogen:DermatitisPathogen:BlastomycesTaxonomy:Feuteromycotina,Haplomycetes,Hyphomycetales,Deuteromycetes,Moniliaceae.Dimorphicfungus.Infectionroute:inhalation.Involvedorgans:lung,skin,bone,CNSorother•••••MainlyoccurringinMainlyoccurringinUSAandCanada,andsporadicinotherEtiologicniches:forest,acidsoil,andwarmregionsnearOverlapendemicregionsbetweenBlastomycosisdermatitidisandHistoplasmosiscapsulatum.DifficulttoisolatefromnaturalCommonlyoccurringinyoungandmid-agedmales(90%).African-AmericansandDiabeticpatientsaresusceptibletoapparentinfectionsofBlastomycesdermatitidis.Dogsarehighlysusceptibleandthuspossibleinfectionsourceofoutbreak.•••••••15001500casesofDermatitisblastomycosiswerereportedinUSAinthepasttwodecades.ReportedcasesinChina(diagnosedbyReportedcasesinChina(diagnosedbySourceofGuoRenshenImportedfromWangPengectHeRushouChenGangDisseminatedNon-MalignantmalariamergedPulmonaryandcutaneousImportedInfectionInfectionroute:inhalation,bittenbyinfectedFungalcellsinalveolicouldcauseacuteinflammationandfinallyformgranuloma.Cell-wallproteinBad1ofBlastomycesdermatitidiscouldmediateitsadhesiontomacrophageandsuppressTNF-αreleasefrommacrophagetointerferewithhostimmuneresponse.Bad1couldalsoinduceantioxidatantmelaninproduction.CellularImmunityplaysavitalroleinpreventingdisseminatedinfectionwhilehumoralimmunitycouldnotcontroltheinfection.••••ClinicalDespiteitshighincidence,lessthan1/3ofpatientshaveapparentClinicalDespiteitshighincidence,lessthan1/3ofpatientshaveapparentsymptomsandmultipleclinicalmanifestations.PulmonaryAsymptomoticorsubclinicalAcutesymptoms:similartobacterialpneumonia,fever,cough,expectorationandhilarinfiltration.Chronicpulmonarylesions:similartopulmonaryTB,necessarytobedifferentiatedfromTBandmalignant••Pulmonaryblastomycosis:Pulmonaryblastomycosis:non-specificnoduleinrightpulmonaryClinicalSkinismostcommoninvolvementsiteindisseminatedinfection,whichmanifestsasverrucousClinicalSkinismostcommoninvolvementsiteindisseminatedinfection,whichmanifestsasverrucousorulcerlesionsinnasaluucosa,oralcavityandlaryngeal.Verrucousplaques,subcutaneousabscess,andUlcerlesions:exudative,andwithsharpSkinlesionsshouldbedifferentiatedfromsquamouscarcinomaandnontuberculousmycobacteriainfection.••••BlastomycesdermatitidiscouldBlastomycesdermatitidiscouldinvadeskin,andmanifestasverrucousplaquesandulcerlesions.UlcerScarsafterUlcerScarsafterulcersDisseminatedinfectionDisseminatedinfectioninClinicalSkeleton