深部真菌感染的流行病学与实验室诊断ppt学习课件.ppt

2019/12/11,.,1,侵袭性真菌病流行病学与实验室诊断,2019/12/11,.,2,2019/12/11,.,3,致病性深部真菌组织胞浆菌球孢子菌副球孢子菌皮炎芽生菌孢子丝菌,条件致病性真菌隐球菌念珠菌曲霉菌毛霉菌肺孢子菌,增加的感染主要是条件致病性真菌,2019/12/11,.,4,念珠菌病,2019/12/11,.,5,念珠菌病,SkinVaginitisUrinarytractMucousmembranesSepticemiaEndocarditisPneumonia,2019/12/11,.,6,口咽念珠菌病,白色念珠菌,置管相关性念珠菌病,白色念珠菌近平滑念珠菌光滑念珠菌热带念珠菌克柔念珠菌,肝脾念珠菌病,通过门脉循环,系统性念珠菌病,通过胃肠道播散,白色念珠菌热带念珠菌克柔念珠菌光滑念珠菌,白色念珠菌,SkinVaginitisUrinarytractMucousmembranesSepticemiaEndocarditisPneumonia,2019/12/11,.,7,2019/12/11,.,8,2019/12/11,.,9,2019/12/11,.,10,2019/12/11,.,11,2019/12/11,.,12,2019/12/11,.,13,2019/12/11,.,14,2019/12/11,.,15,过去的20年中院内念珠菌属的血行感染明显提高,500%,DatafromLewis171:388-416.KoldehoffMetal.AmJHematol.2005;79:158-163.,2019/12/11,.,26,念珠菌肺炎Candidapneumonia,45岁，女，急性髓细胞性白血病acutemyeloblasticleukemia，出现发热.胸片示右上肺实变.经皮肤细针穿刺活检标本specimenofpercutaneousfine-needlebiopsy分离到白色念珠菌Calbicans,2019/12/11,.,27,曲霉菌病,2019/12/11,.,28,2019/12/11,.,29,2019/12/11,.,30,7960例尸检深部真菌感染病原体构成,JOURNALOFCLINICALMICROBIOLOGY,June1999,p.17321738,2019/12/11,.,31,JOURNALOFCLINICALMICROBIOLOGY,June1999,p.17321738,2019/12/11,.,32,2019/12/11,.,33,侵袭性肺曲菌病高危因素,中性粒细胞减少时间延长3wk移植(包括器官移植和HSCT)受体激素的应用，尤其是长时间大剂量血液系统恶性肿瘤细胞毒性药物HIV感染进展期,CHEST2002;121:19881999),2019/12/11,.,34,2019/12/11,.,35,2019/12/11,.,36,2019/12/11,.,37,2019/12/11,.,38,2019/12/11,.,39,2019/12/11,.,40,2019/12/11,.,41,2019/12/11,.,42,2019/12/11,.,43,2019/12/11,.,44,2019/12/11,.,45,2019/12/11,.,46,2019/12/11,.,47,2019/12/11,.,48,Aspergillusspecies:ClinicalDisease,Spectrumofhumandisease,Invasiveaspergillosis,Colonizationofrespiratorytract,Pulmonaryaspergilloma/mycetoma,Allergicbronchopulmonaryaspergillosis16:875-95,2019/12/11,.,49,曲菌病肺部病变影像学的动态变化,晕轮征-atypical-新月征,CAILLOTetal.JClinOncol2001;19:253,2019/12/11,.,50,UnequivocalHalosignsurroundinganodule,Herbrecht,Denningetal,NEJM2002;347:408-15.,Smallvesselangioinvasion,Halo,2019/12/11,.,51,Pulmonarynodulesausefulfeatureifinvasivepulmonaryaspergillosis,CTfeaturesin235CTsinpatientswithIPAMacronodule(1cm)221(94%)Halo143(60%)Consolidation71(30%)Macro-nodule,infarctshaped63(27%)Cavitarylesion48(20%)Airbronchograms37(16%)Clustersofsmallnodules(1cm)25(11%)Pleuraleffusion25(11%)Aircrescentsign24(10%)Non-specificgroundglass21(9%),Greenesubmitted,fromHerbrechtNEnglJMed2002:347:408.,2019/12/11,.,52,肺部曲霉菌感染痰液标本的检测,肺泡灌洗液阳性率50%,痰培养阳性率8%,PATERSON,SINGHMedicine1999;78:123,2019/12/11,.,53,曲菌球Aspergilloma,A22-year-oldmanwithdiabetesmellituspresentedwithhemoptysis.Chestradiographyshowsacavitarynodularlesionwithair-crescentintherightlowerlung.HeunderwentwedgeresectionandAspergillusspecieswasfound.,2019/12/11,.,54,侵袭性曲菌病Invasiveaspergillosis,A26-year-oldwomanwithacutelymphoblasticleukemiastatuspostbonemarrowtransplantationpresentedwithfever.Chestradiographyshowsaconsolidationintheleftupperlungfield.Aspergillusnigerwasisolatedfromspecimenbypercutaneousfine-needleaspiration.,2019/12/11,.,55,隐球菌病,2019/12/11,.,56,肺和脑部隐球菌感染,2019/12/11,.,57,英国隐球菌病（19801999）,Year,No.cases,AIDS-defining241824illness,Knightetal.1993JInfect27:185-191,2019/12/11,.,58,2019/12/11,.,59,隐球菌球Cryptococcoma,53岁，女性，咳嗽，无基础疾病胸片示右中肺野结节胸腔镜，病理显示隐球菌球,2019/12/11,.,60,隐球菌肺炎Cryptococcalpneumonia,34岁，男，没有基础疾病，干咳，发热，呼吸困难；胸片示双下肺实变；吸引物隐球菌抗原滴度高达1:2560,2019/12/11,.,61,病例,男性，33岁，因“干咳2月余”入院，偶伴喘息，无发热盗汗，阿奇霉素抗感染及平喘治疗后症状无好转。CT示“右下肺散在片状影，并可见小空洞形成”，抗感染后随访“右下肺病灶无明显好转”。既往史：自诉幼时曾患风疹、腮腺炎，常患“病毒感染”，病前有带状疱疹史。查体：体温正常，呼吸音清，右下肺可及湿啰音。实验室检查血常规：正常；ESR正常；痰、BALF：抗酸染色(-)，病理细胞(-)；血清GM检测：I0.2990.5,2019/12/11,.,62,2019/12/11,.,63,2006年2月支气管镜检查行TBLB：活检报告纤维结缔组织及肺组织，其间见肉芽肿性炎，并见霉菌孢子结构，特殊染色阳性，考虑霉菌感染。,HE染色,PAS染色,血清乳胶凝集试验隐球菌：阳性，滴度1:640,2019/12/11,.,64,男，61岁，5月前鼻咽癌行放化疗；1周前检查发现双肺阴影。偶有干咳，无咯血、胸痛。胸部CT示双肺多发片状、类结节状阴影。支气管镜TBLB病理：慢性炎症。CT引导下经皮肺穿刺病理：炎性病变。2次隐球菌乳胶定性试验：阳性；2次乳胶凝集定量试验：滴度（1：80）,2019/12/11,.,65,FungalSpeciesIdentifiedFrom140PatientsWithPulmonaryFungalInfections,ChenKY,KoSH,HsuehPR,etal.PulmonaryFungalInfection.Chest2001;120:177-184,2019/12/11,.,66,实验室诊断与实践,2019/12/11,.,67,侵袭性深部真菌感染的诊断,确诊Proven宿主临床表现组织病理微生物学临床诊断Probable宿主临床表现微生物学拟诊Possible宿主微生物学宿主临床表现,2019/12/11,.,68,肺部真菌感染的诊断项目,宿主临床表现主要指标：晕轮征、新月征、空洞次要指标：咳嗽、胸痛、咯血、呼吸困难、胸膜摩擦音、新的肺部浸润但不够主要指标组织病理微生物学涂片与培养抗原检测：半乳糖甘露聚糖（GM）是真菌细胞壁上的多聚抗原；1-3-D-葡聚糖也是一种真菌抗原成分；隐球菌荚膜抗原（血清）基因检测：PCR,2019/12/11,.,69,2019/12/11,.,70,SpecificpulmonaryinfiltratesonCTscan,2019/12/11,.,71,DIAGNOSTICTESTS,culturehistology,antibodyantigenbloodcultures,PCR1-3-D-glucanimaging/radiology,C-ReactiveProtein(CRP),procalcitonin(PCT),interleukin-6(IL-6),2019/12/11,.,72,欧洲癌症治疗研究组织(EORTC)/美国国家过敏症与传染病研究所霉菌病研究组(MSG),半乳甘露聚糖(GM)试验：阈值调整，以期提高检测敏感度。受检测人群中曲霉病的发病率。GM试验的阳性预测值在曲霉病发病率为5%的人群中为31%,而在发病率为20%的人群中为69%。更适于高危人群的筛查，连续监测可提高敏感性G试验(真菌细胞壁-D-葡聚糖成分)：敏感性很好，但特异度尚需提高。核酸扩增：缺乏标准化试剂盒，尚未被EORTC/MSG批准,2019/12/11,.,73,AntigenDetectionGMEIAStudies,2019/12/11,.,74,AntigenDetectionGMEIA,ComparisonofDiagnosticTestsforProvenIA,MaertensetalJID2002;186:1297-1306,2019/12/11,.,75,GMEIAFalsePositiveResults,MucositisTranslocationofintra-luminaldietaryGMand/orcross-reactingantigensAntibioticsPiperacillin-tazobactam,other-lactamsOtherfungi,including-Penicilliumsp.Paecilomycessp.Children,particularlyneonatesBifidobacteriumsp.withcross-reactingantigensOccultinfection,2019/12/11,.,76,AntigenDetectionGMEIA,GMEIAOtherSpecimensOnlyvalidatedinserumBALfluidSensitivities76-90%,specificities94-100%MoresensitivethanserumCSFLowercut-offUrineSomerenalexcretionLargevolume,abletoconcentrateStudiesneededtodefinesensitivity/specificity,2019/12/11,.,77,2019/12/11,.,78,【病例】心脏移植后肺部阴影,男，61岁，4年前开始出现活动后心悸、气促，诊断为“心肌炎后心肌病”，于2007年5月21日于全麻下行原位心脏移植术。术后第19天出现发热、体温最高达39.5，咳少量黄痰，无气急、咯血、胸痛等症状。体检：一般情况好，呼吸频率16次/分，无气急、紫绀。双肺呼吸音清，未闻及干湿啰音。,2019/12/11,.,79,2007-6-15胸部CT:右肺上叶见一团块状高密度影，约4.53.0cm，周围有晕轮征；左肺上叶见一结节影1.01.0cm。余两肺散在片状高密度影，边缘模糊。,2019/12/11,.,80,痰普通培养4次，其中3次为黄曲霉（）；痰真菌培养4次，其中3次为黄曲霉（）。血清半乳甘露聚糖（GM）测定2次分别为0.780.43。血常规示：WBC7.7*109/LN%89.7%。,2019/12/11,.,81,予单用卡泊芬净50mgqd治疗21天，停用其他抗菌药物，随访胸部CT病变好转。由于卡泊芬净无口服制剂，改为伏立康唑治疗静脉点滴2周，病灶明显缩小，再改用口服，随访病情持续好转。,2019/12/11,.,82,2007-6-22胸部CT:左上肺结节内出现空洞，右上肺团块状高密度影周围晕征吸收，病灶内出现小空洞,2019/12/11,.,83,2007-8-4胸部CT:左上肺结节明显较前吸收，右上肺团块影部分吸收消散，边缘模糊。,2019/12/11,.,84,2007-7-18胸部CT:右上肺病灶进一步吸收，病灶大小约1.51.5cm,2019/12/11,.,85,【病例】两肺结节伴空洞,男，59岁，1周前受凉后出现咳嗽、少量白痰，伴畏寒、发热，38.4C，无胸痛、咯血。胸部CT示“两肺弥漫性肺癌？”，2006年10月17日支气管镜检查后入院。既往无体健，吸烟史30支/天40年。,2019/12/11,.,86,2019/12/11,.,87,两肺弥漫性结节影，考虑特异性感染（真菌或结核）可能大，MT不除外,2019/12/11,.,88,2019/12/11,.,89,纤支镜：各支气管管腔通畅，右下叶背段管口见少许白色分泌物，右上叶前段活检肺组织六块肺组织真菌涂片找见烟曲霉菌丝、孢子。WBC3.5*109/L,N62.4%；ESR:36mm/H；血糖：20+mmol/L血GM（2006-10-27）：1.31,2019/12/11,.,90,最初TBLB病理：慢性炎症TBLB组织涂片：肺曲霉菌二性霉素B抗真菌治疗30天总剂量达750mg，此后改为伊曲康唑口服。,2019/12/11,.,91,2007-11-13两性霉素B治疗14天后，双肺病灶有所吸收。,2019/12/11,.,92,2019/12/11,.,93,【病例】乳腺癌根治术后化疗6次再放疗，咳嗽气急半年伴间歇性发热,女，47岁，浙江象山人。6月余前出现咳嗽、少量白色泡沫样痰，伴气急，时有发热。无咯血、胸痛等。4年前因乳腺癌行双侧乳癌根治术，术后化疗6次。1年前行胸部CT检查发现纵隔淋巴结肿大并伴有锁骨上淋巴结肿大，活检病理示找到癌细胞，并予放疗。胸部CT示双肺上叶及下叶背段靠近纵隔处条索网格状