肺隐球菌病课件

肺隐球菌病（PC，pulmonarycryptococcosis）

---从一个病例谈起复旦大学附属华山医院北院呼吸科张有志1可编辑课件PPT病史介绍患者，女性，47岁主述：因“反复咳嗽伴胸痛1月”入院（B院）现病史：患者于2010.9.5无明显诱因出现咳嗽，少量白痰，伴右侧胸痛，阵发性钝痛，深吸气时明显，无放射痛，无发热，无呕吐、头痛，某A院行胸部CT示“右下肺炎”，予以莫西沙星静滴8天患者咳嗽、胸痛有所缓解，继续口服莫西沙星6天，2010.9.27复查CT无吸收。于2010.10.12就诊B院。既往：体健。否认性病冶游史。家中曾养宠物（鸽子、狗）。查体：T：37.9℃，浅表淋巴结不大，右下肺可及湿啰音。辅助检查：血常规、肝肾功能、D-二聚体正常；ESR：65mm/h，CRP：48mg/L；血气分析正常；HIV（-）PPD试验阴性；LA试验、G试验阴性（送至C院检测）2可编辑课件PPT2010.9.6A院CT2010.9.27A院CT3可编辑课件PPT病史介绍A院气管镜检查：镜下：未见明显异常；右下肺灌洗和刷检：未见恶性细胞、TB阴性。

4可编辑课件PPT2010.10.12B院

CT引导下经皮肺穿刺病理结果确诊：肺隐球菌病上皮样肉芽肿性病变；成堆隐球菌5可编辑课件PPT几点疑问真菌病一般都是免疫功能低下的患者隐球菌如何侵袭到肺的LA试验阴性肺隐球菌病CT表现和肺炎一样6可编辑课件PPT关于隐球菌Ｃｒｙｐｔｏｃｏｃｃｕｓ带厚荚膜的酵母菌（乳胶凝集试验）腐生菌：土壤、鸽粪、霉烂蔬菜、水果等感染部位：中枢神经系统、皮肤、肺

感染途径：吸入呼吸道经血行播散到其它部位分型：17个种、18个变种（新生隐球菌及变种具有致病性）7可编辑课件PPTEpidemiologyIAmulticentreretrospectivestudyofpulmonarymycosisclinicallyprovenfrom1998to2007Totally474casesofpulmonarymycosisfrom16centersin10cities.pulmonaryaspergillosis(180cases，37．9％)pulmonarycandidiasis(162cases，34．2％)pulmonarycryptococcosis(74cases，15．6％)pneumocystiscafiniipneumonia(23cases，4.8％)pulmonarymucormycosis(10cases，2．1％)中华结核和呼吸杂志，2011,34(2)8可编辑课件PPTEpidemiologyIIMeta-AnalysisofClinicalManifestationsofPulmonaryCryptococcosisinChinaMainland69.7%patientshadnounderlyingdiseases．Thecommonunderlyingdiseaseswereacquiredimmunedeficiencysyndrome(AIDS)diabetesmalignanttumor

中国临床医学，2013,20（3）：351-3549可编辑课件PPTEpidemiologyIIIRetrospectiveinvestigationof151pulmonarycryptococcosisnon-HIVcasesbetween1977and201244.4%patientshadnoUDs.ThecommonUDswerediabetes(32.1%)hematologicdisease(22.6%)collagendisease(22.6%)JapaneseSocietyofChemotherapyandTheJapaneseAssociationforInfectiousDiseases.JInfectChemother.2014Oct29

10可编辑课件PPTEpidemiologyIV219patientswithprovencryptococcosisat20hospitals

inTaiwan,1997-2010210isolateswereC.neoformans(95.9%);9isolateswereC.gattii(4.1%).

15.4%didnothaveanyunderlyingcondition.

HIVinfectionwasthemostcommonunderlyingcondition(54/219,24.6%).AmongHIV-negativepatients,liverdiseases(HBVcarrierorcirrhosis)werecommon(30.2%)TaiwanInfectiousDiseasesStudyNetworkforCryptococcosis.

PLoSOne.2013Apr17;8(4):e61921.11可编辑课件PPTEpidemiologyVClinicalanalysisof76patientspathologicallydiagnosedwithpulmonarycryptococcosis.Of76patients(54malesand22females),41(53.95%)wereimmunocompetentand35outofthe41wereasymptomatic.

ShanghaiPulmonaryHospital.EurRespirJ.2012Nov;40(5):1191-200.12可编辑课件PPTsummaryapproximatelyhalfofpatientshadnounderlyingdiseasesasignificantnumberofpatients

wereasymptomatic13可编辑课件PPTpathogenesisThecapsuleisthemostimportantvirulencefactorofthefungalpathogenCryptococcusneoformans.ThestructureProductionOfthecapsuleadhesionofCryptococcusneoformanstoepitheliallungcellsprotectiveimmuneresponsesagainstcryptococcosis14可编辑课件PPTThestructureofcapsuleThisstructureconsistsofhighlyhydratedpolysaccharides,includingglucuronoxylomannan(GXM)，葡萄糖醛酸木糖甘露聚糖galactoxylomannan(GalXM)，半乳糖木糖甘露聚糖mannoproteins(MPs)，甘露糖蛋白，lessthan1%ofthecapsularweight15可编辑课件PPTProductionOfthecapsuleICA/CO2-sensingpathways

.1Regulationofcapsulesynthesisbycarbondioxide．JClinInvest，1985，76(2):508-516．2ComparativetranscriptomeanalysisoftheCO2sensingpathwayviadifferentialexpressionofcarbonicanhydraseinCryptococcusneoformans.Genetics.2010Aug;185(4):1207-19.16可编辑课件PPTProductionOfthecapsuleII

cryptococcalpolysaccharidesynthesisisincreasedbylimitationofferricironavailabilitytothecellandbydissolvedCO2,andthetwoeffectsareadditive.Regulationofcryptococcalcapsularpolysaccharidebyiron.JInfectDis.1993Jan;167(1):186-90.17可编辑课件PPTProductionOfthecapsuleIIIcapsuleenlargementinlivingC.neoformanscellswasinfluencedbyCa(2+)intheculturemedium.

EukaryotCell.2007Aug;6(8):1400-10.

18可编辑课件PPTProductionOfthecapsuleIVbasedontheaxiallengtheningofPSmolecules.CapsuleofCryptococcusneoformansgrowsbyenlargementofpolysaccharidemolecules.ProcNatlAcadSciUSA.2009Jan27;106(4):1228-33.PS，etccapsule?alveolarmicroenvironment19可编辑课件PPTadhesiontoepitheliallungcells

anadhesion-likeinteractionbetweenMPonthefungalsurfaceandthecomplementaryreceptormoleculesontheepithelialcells.

FrontCellInfectMicrobiol.2014Aug19;4:106.20可编辑课件PPTPhagocytosisdefenceSizeofCryptococcusneoformans.DynamicchangesinthemorphologyofCryptococcusneoformansduringmurinepulmonaryinfection.

GXMagainstalveolarmacrophages(AM).Mechanismsofimmuneevasioninfungalpathogens.

1Microbiology.2001Aug;147(Pt8):2355-65.2CurrOpinMicrobiol.2011Dec;14(6):668-75.21可编辑课件PPTimmuneresponseSP-DincreasessusceptibilitytoC.neoformansinfectionbypromotingC.neoformans-drivenpulmonaryIL-5andeosinophilinfiltration.Th1/Th2cytokineimbalance.BcellsprovideafirstlineofdefenseduringpulmonaryC.neoformansinfectioninmice

1GenetMolRes.2013Nov18;12(4):5733-422InfectImmun.2014Feb;82(2):683-933JImmunol.2012Dec15;189(12):5820-3022可编辑课件PPTMyopinioniChangealveolarmicroenvironmentAbrogationofIL-4receptor-α-dependentalternativelyactivatedmacrophagesissufficienttoconferresistanceagainstpulmonarycryptococcosisdespiteanongoingT(h)2response.

IntImmunol.2013Aug;25(8):459-70.23可编辑课件PPTRadiologyIPeripherallydistributedpulmonarynodules/massesweremostcommonlyseen.JapaneseSocietyofChemotherapyandTheJapaneseAssociationforInfectiousDiseases.JInfectChemother.2014Oct29Radiological(computedtomography)findingsshowedpredominantlyperipheralfindings(85.53%)includingnodularmasses(55.26%),pneumonicinfiltrates(23.68%)andmixedtype(21.05%).ShanghaiPulmonaryHospital.EurRespirJ.2012Nov;40(5):1191-200.71.8%patientswerecharacterizedbynodularlumpshadows;23.8%byflake-likeinfiltratedshadows，and7.4%haddiffusemixedlesions．ZhongshanHospital.ChineseJournalofClinicalMedicine，201324可编辑课件PPTRadiologyII

CTscanfindingsof29immunocompetentand43immunocompromisedpatients

Pulmonarynodules/masses,eithersolitaryormultiple,werethemostcommonCTfinding,presentin65(90.3%)ofthe72patients

Cavitationswithinnodules/massesweremorecommonlyseeninimmunocompromisedpatients,especiallyAIDSpatientsairbronchogramsweremorecommonlyseeninimmunocompetentpatientsPulmonarycryptococcosis:comparisonofCTfindingsinimmunocompetentandimmunocompromisedpatients.

ActaRadiol.2014Apr22.25可编辑课件PPTMyopinioniiMolecular/functionalradiology26可编辑课件PPTcurrentsituationindiagnosis43.42%(33/76)wereinitiallymisdiagnosed,oftenascancerbyfalse-positive(18)FDG-PETFailureofthecryptococcalserumantigentesttodetectprimarypulmonarycryptococcosisinpatientsinfectedwithhumanimmunodeficiency

virus26.2%（17/65）wereconfirmedbysurgery1ShanghaiPulmonaryHospital.EurRespirJ.2012Nov;40(5):1191-200.