肺隐球菌病ppt课件.ppt

肺隐球菌病 PC pulmonarycryptococcosis 从一个病例谈起 1 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 2010 9 6A院CT 2010 9 27A院CT 3 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 2010 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 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 关于隐球菌 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 EpidemiologyI Amulticentreretrospectivestudyofpulmonarymycosisclinicallyprovenfrom1998to2007Totally474casesofpulmonarymycosisfrom16centersin10cities 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 EpidemiologyII Meta AnalysisofClinicalManifestationsofPulmonaryCryptococcosisinChinaMainland69 7 patientshadnounderlyingdiseases Thecommonunderlyingdiseaseswereacquiredimmunedeficiencysyndrome AIDS diabetesmalignanttumor中国临床医学 2013 20 3 351 354 9 EpidemiologyIII Retrospectiveinvestigationof151pulmonarycryptococcosisnon HIVcasesbetween1977and201244 4 patientshadnoUDs ThecommonUDswerediabetes 32 1 hematologicdisease 22 6 collagendisease 22 6 JapaneseSocietyofChemotherapyandTheJapaneseAssociationforInfectiousDiseases JInfectChemother 2014Oct29 10 EpidemiologyIV 219patientswithprovencryptococcosisat20hospitalsinTaiwan 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 EpidemiologyV Clinicalanalysisof76patientspathologicallydiagnosedwithpulmonarycryptococcosis Of76patients 54malesand22females 41 53 95 wereimmunocompetentand35outofthe41wereasymptomatic ShanghaiPulmonaryHospital EurRespirJ 2012Nov 40 5 1191 200 12 summary approximatelyhalfofpatientshadnounderlyingdiseasesasignificantnumberofpatientswereasymptomatic 13 pathogenesis ThecapsuleisthemostimportantvirulencefactorofthefungalpathogenCryptococcusneoformans ThestructureProductionOfthecapsuleadhesionofCryptococcusneoformanstoepitheliallungcellsprotectiveimmuneresponsesagainstcryptococcosis 14 Thestructureofcapsule Thisstructureconsistsofhighlyhydratedpolysaccharides 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 ofthecapsularweight 15 ProductionOfthecapsuleI CA CO2 sensingpathways 1Regulationofcapsulesynthesisbycarbondioxide JClinInvest 1985 76 2 508 516 2ComparativetranscriptomeanalysisoftheCO2sensingpathwayviadifferentialexpressionofcarbonicanhydraseinCryptococcusneoformans Genetics 2010Aug 185 4 1207 19 16 ProductionOfthecapsuleII cryptococcalpolysaccharidesynthesisisincreasedbylimitationofferricironavailabilitytothecellandbydissolvedCO2 andthetwoeffectsareadditive Regulationofcryptococcalcapsularpolysaccharidebyiron JInfectDis 1993Jan 167 1 186 90 17 ProductionOfthecapsuleIII capsuleenlargementinlivingC neoformanscellswasinfluencedbyCa 2 intheculturemedium EukaryotCell 2007Aug 6 8 1400 10 18 ProductionOfthecapsuleIV basedontheaxiallengtheningofPSmolecules CapsuleofCryptococcusneoformansgrowsbyenlargementofpolysaccharidemolecules ProcNatlAcadSciUSA 2009Jan27 106 4 1228 33 PS etccapsule alveolarmicroenvironment 19 adhesiontoepitheliallungcells anadhesion likeinteractionbetweenMPonthefungalsurfaceandthecomplementaryreceptormoleculesontheepithelialcells FrontCellInfectMicrobiol 2014Aug19 4 106 20 Phagocytosisdefence SizeofCryptococcusneoformans DynamicchangesinthemorphologyofCryptococcusneoformansduringmurinepulmonaryinfection GXMagainstalveolarmacrophages AM Mechanismsofimmuneevasioninfungalpathogens 1Microbiology 2001Aug 147 Pt8 2355 65 2CurrOpinMicrobiol 2011Dec 14 6 668 75 21 immuneresponse SP DincreasessusceptibilitytoC neoformansinfectionbypromotingC neoformans drivenpulmonaryIL 5andeosinophilinfiltration Th1 Th2cytokineimbalance BcellsprovideafirstlineofdefenseduringpulmonaryC neoformansinfectioninmice1GenetMolRes 2013Nov18 12 4 5733 422InfectImmun 2014Feb 82 2 683 933JImmunol 2012Dec15 189 12 5820 30 22 Myopinioni ChangealveolarmicroenvironmentAbrogationofIL 4receptor dependentalternativelyactivatedmacrophagesissufficienttoconferresistanceagainstpulmonarycryptococcosisdespiteanongoingT h 2response IntImmunol 2013Aug 25 8 459 70 23 RadiologyI Peripherallydistributedpulmonarynodules 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 2013 24 RadiologyII CTscanfindingsof29immunocompetentand43immunocompromisedpatientsPulmonarynodules masses eithersolitaryormultiple werethemostcommonCTfinding presentin65 90 3 ofthe72patientsCavitationswithinnodules massesweremorecommonlyseeninimmunocompromisedpatients especiallyAIDSpatientsairbronchogramsweremorecommonlyseeninimmunocompetentpatientsPulmonarycryptococcosis comparisonofCTfindingsinimmunocompetentandimmunocompromisedpatients ActaRadiol 2014Apr22 25 Myopinionii Molecular functionalradiology 26 currentsituationindiagnosis 43 42 33 76 wereinitiallymisdiagnosed oftenascancerbyfalse positive 18 FDG PETFailureofthecryptococcalserumantigentesttodetectprimarypulmonarycrypto