主要致病性真菌.ppt

1,主要致病性真菌,浅部真菌感染（致病性真菌感染和条件致病性真菌感染）深部真菌感染（致病性真菌感染和条件致病性真菌感染）,2,浅部感染真菌,表面感染真菌皮肤癣真菌皮下组织真菌感染,3,4,表面感染真菌,位置：寄居于人体皮肤和毛干的最表层。因不接触组织细胞，很少引起宿主细胞反应统称：角层癣菌代表：秕糠马拉癣菌(Malasseziafurfur)症状：由于此菌能产生对黑色素细胞有抑制作用的二羧酸，使花斑癣局部色素减退，如汗渍斑点，俗称汗斑。诱发因素为高温多汗,5,Malasseziafurfur,Tineaversicoloronskinsurface(sweatstain)ThelesionsaresmallhypopigmentedorhyperpigmentedmaculesMostcommonsite:back,underarm,upperarm,chest,neckMostcommoninadolescentandyoungadultmalesAssociatedwithincreasedsweating,6,PityriasisversicolorshowinghyperpigmentedlesionsinaCaucasianandhyphopigmentedlesionsinanAustralianAborigine,7,CultureofMalasseziafurfuronDixonsagar(containsglycerolmono-oleate),8,Piedraiahortae(何德毛结节菌),ItusuallyaffectedthescalphairThenodulesaredarkerincolor,harder,andmorefirmlyattachedtothehairsBlackPiedra,9,Piedraiahortaeformsahardsuperficialpigmentednodulearoundthehairshaft(在毛干上形成硬的黑色结节，如沙粒状),10,Fungalotitisexterna,FungalinfectionoftheexternalauditorycanalCausedbyseveralspeciesofAspergillus(mostoftenA.niger),butCandidaalbicansisalsocapableofinfectingthissiteThemajorsymptomsareitchingandfeelingoffullnessinear,11,12,皮肤癣真菌,引起皮肤浅部感染皮肤癣是人类最多见的真菌病统称：皮肤癣菌，大约40多个种，分属于3个属嗜角质蛋白，37不能生长，侵犯部位：角化的表皮，毛发，指（趾）甲病理变化：由真菌增殖及代谢产物刺激宿主引起,13,致病性,指（趾）甲皮肤毛发毛癣菌属+表皮癣菌属+-小孢子癣菌属-+,一种皮肤癣菌可在不同部位引起病变相同部位的病变也可由不同的皮肤癣菌引起,14,15,TineapediscausedbyT.rubrum.Sub-clinicalinfection(left)showingmildmacerationunderthelittletoeandmoresevereinfection(right)showingextensivemacerationofalltoewebspaces,Tineaistransmittedviathefeetbydesquamatedskinscalesinsubstrateslikecarpetandmatting.,16,手足癣治疗原则,水疱型温和搽剂和霜剂角化过度型先角质剥脱剂，再用抗真菌霜剂浸渍糜烂型粉剂收干，抗继发感染，再温和抗真菌,17,TineaUnguium,usuallycausedbyTrichophytonsp,18,甲癣治疗原则,局部治疗甲涂剂系统治疗伊曲康唑，特比萘芬等联合治疗配合拔甲或削甲治疗,19,TineaCorporis:causedbyM.canis,followingcontactwithinfectiouskittens,20,TineaCruris(Jockitch):Infectionofthegroin,mainlyseeninmen,21,TineaCapitis(scalpringworm),Tineafavosa,发内孢子,22,TineaCapitis(scalpringworm),Tineaalba,发外孢子,23,TineaCapitis(scalpringworm),脓癣,24,头癣治疗原则,剪发洗发搽药服药消毒,25,Candidiasisofskin,mucousmembranesandnails,PredisposingfactorsInfancy,pregnancy,oldageDisordersofimmunefunction,e.g.,leukemia,corticosteroidtherapyChemotherapy,e.g.,immunosuppressive,antibioticEndocrinedisease,e.g.,diabetesmellitusCarcinoma,26,念珠菌性间擦疹,好发部位：腋窝、乳房下、腹股沟、会阴，多见于婴儿及肥胖者。,27,Cutaneouscandidiasis:includingInterdigitalcandidiasis,diapercandidiasis,paronychiaandonychomycosisVulvovaginalcandidiasisandbalanitis,Interdigitalcandidiasis,Candidiaonychomycosisandparonychia,28,Oropharyngealcandidiasis:includingthrush,glossitis,stomatitisandangularcheilitis,Oralthrush,29,皮下组织真菌感染,主要有孢子丝菌和着色真菌申克孢子丝菌，属腐生性真菌，常因外伤接触带菌的花草等引起感染。此菌可引起孢子丝菌下疳。此菌也可引起深部感染。是一种二相性真菌。着色真菌感染发生在暴露部位，称着色真菌病。我国主要有卡氏枝孢霉和裴氏着色芽生菌。,30,Sporotrichosis,此菌可经微小损伤侵入皮肤，然后沿淋巴管分布，引起亚急性或慢性肉芽肿，使淋巴管形成链状硬结，称为孢子丝菌下疳。,31,ChromomycosisInfectionsoccurinexposedareas,skinlesionsbecomedark,socalledchromomycosisRepresentivespecies:Cladosporiumcarrianii,Fonsecaeapedrosoi,etc.Aresaprophyticfungi,usuallyentersthebodybytrauma,32,经外伤侵入丘疹结节结节融合成疣状或菜花状斑痕形成影响淋巴回流肢体象皮肿,33,Chromomycosis,ChronicverrucouschromoblastomycosisofthehandduetoCladophialophoracarrionii,34,Mycetoma足分枝菌病,是由多种放线菌或真菌引起的一种慢性化脓性肉芽肿性疾病，主要感染足部，以肿胀、窦道和颗粒为特征。causedbyfungiarecalledeumycetoma(40%)Actinomycetomaiscausedbyactinomycetes(60%)Itischaracterizedbytheformationofabscess,whichcontainlargeaggregatesoffungaloractinomycetefilamentsknownasgrains,35,EumycetomaDarkgrainsMadurellamycetomatisLeptosphaeriasenegalensisExophialajeanselmeiPalegrainsFusariumsp.Acremoniumsp.Scedosporiumapiospermum,ActinomycetomaWhite-yellowgrainsActinomaduramaduraeNocardiabrasiliensisYellow-browngrainsStreptomycessomaliensisRed-pinkgrainsActinomycetomapellettieri,36,深部真菌感染,引起深部感染的真菌包括两大类：致病性真菌与条件致病性真菌致病性真菌主要有组织胞浆菌、球孢子菌、副球孢子菌和芽生菌，这些真菌均属二相性。多见于美洲，我国极少见。它们侵袭深部组织和内脏以及全身，引起慢性肉芽肿样炎症、溃疡和坏死。条件致病性真菌包括有：念珠菌、隐球菌、曲霉菌与毛霉菌、肺孢子菌等。,37,Characteristicsofsystemicdimorphicmycoses,Areuncommon,oftenoccursinendemicareasMostinfectionsareasymptomaticorself-limitinginimmune-compromisedhosts,infectionsareoftenfatalThepatternofinfectionaresimilarRouteofacquisitionisinhalationPulmonaryinfectionDisseminatedinfection(Blood,Bonemarrow,BrainandCSF,Joint),38,Coccidioidomycosis,Coccidiodesimmitisisconsideredtobethemostvirulentoffungalpathogens.Restrictedtohot,semi-aridareasofSWUSAandMexico.Growsinthesoil,butinhalationofasinglesporecaninitiateinfection.,Ininfectedtissues,C.immitisappearsasamixtureofendosporesandspherules.,Conidia,Spherules,39,Coccidioidomycosis:,Encounter:Myceliumfoundindry,dustysoil.ContactbyinhalationofarthroconidiaSpread:Mostcommonlyanasymptomaticselflimitedpulmonarydisease,butmayspreadviathebloodtoskin,softtissues,bones,jointsandmeninges.ImmuneResponse:T-cellmediated(Th-1)EvasionofDefenses:Resistanttokillingbyphagocytes-proteinrich,hydrophobicouterwall-alkalinehaloassociatedwithureaseE.Damage:secretedproteinasesbreakdowncollagen,elastinhemoglobin,IgGbutcanspreadtootherorgans.Mostprevalentinmales40-60yearsofageandchildren.,Blastomycesdermatitidis,Dimorphicorganismoriginatesinthesoilandinfectionensuesbyinhalationofspores.Convertstoyeastinanimalhostsorat37oinvitro.,47,Blastomycosis,Encounter:Mostcasesareinsouthern,central,andsoutheasternUSA.Infectionisbyinhalationofspores.Spread:Thepulmonaryinfectioniseitherself-limitedorprogressive.Disseminationoftenoccurstotheskinandtothebone-80%ofpatientshavelargeskinlesions;alargenumberalsohavegranulomatouspulmonarylesions.RiskFactors:Occupationalcontactwithsoil;owningadog.Livinginendemicarea.EvasionofDefenses:EscapesphagocytosisbyneutrophilsandmonocytesbysheddingitssurfaceantigenafterinfectionDamage:Consequenceoftheimmuneresponsetotheorganismskinlesions,respiratoryinfiltrates.Diagnosis:basedonclinicalfindingsandmicroscopicdetectionoforganismsintissuespecimens,48,AmphotericinBisthedrugofchoiceforrapidlyprogressiveblastomycosisItraconazoleorKetoconazoleforlessseverecases,Immuneresponse,1.Alveolarmacrophageprovideafirstlineofdefense.2.T-cellstimulatedPMNskillBlastomycescellsbyoxidativemechanisms.ConidiaaremoresensitivetokillingbyPMNsbecauseyeastaretoobig.TH-1responseisofprimaryimportance,Blastomycosis,Treatment,49,Opportunisticfungalinfections,Opportunisticmycosesarefungalinfectionsthatdonotnormallycausediseaseinhealthypeople,butdocausediseaseinpeoplewithweakenedimmunedefenses(immunocompromisedpeople).Weakenedimmunefunctionmayoccurduetoinheritedimmunodeficiencydiseases,drugsthatsuppresstheimmunesystem(cancerchemotherapy,corticosteroids,drugstopreventorgantransplantrejection),radiationtherapy,infections(e.g.,HIV),cancer,diabetes,advancedageandmalnutrition.Themostcommoninfectionsare:CandidiasisCryptococcosisAspergillosisPneumocystiscariniipneumonia(PCP)Penicillosismarneffei,50,白假丝酵母菌(Candidaalbicans),形态：圆形或卵圆形单细胞真菌，革兰阳性繁殖：出芽繁殖，形成假菌丝，在组织易形成芽生孢子培养：普通琼脂、血琼脂与沙保培养基需氧。室温或37甚至42生长良好菌落灰白色或奶油色，表面光滑，带有浓厚的酵母气味。有大量向下生长的营养假菌丝，呈类酵母型。在玉米粉培养基上可长出厚膜孢子,属于假丝酵母菌属，俗称白念，为酵母型真菌，是条件致病菌可引起皮肤、黏膜和内脏的急性或慢性炎症，即念珠菌病，是最常见的深部感染真菌病，口腔念珠菌病是艾滋病患者最先出现的继发性感染。生物学特性,51,假菌丝和厚膜孢子,52,Systemicinvolvement,UrinarytractinfectionPulmonarycandidiasisEndocarditisMeningitisCandidaemia(septicaemia)Infancy,oldage,pregnancy,prolongantibiotic,HIV/AIDS,diabetes,53,微生物检查：,1、直接镜检：同时见出芽的念珠菌与假菌丝2、分离培养与鉴定：假菌丝，芽生孢子芽管形成试验/厚膜孢子形成试验3、白色念珠菌细胞壁甘露聚糖抗原/ELISA特异性高但敏感性低4、动物试验：小鼠,54,Cryptococcusneoformans,属于隐球菌属，为酵母型真菌传染源是鸽子，人因吸入鸽粪污染的空气而感染主要引起肺和脑的急性、亚急性或慢性感染。生物学特性,圆形，有肥厚荚膜（一般厚度是直径的两倍）染色：一般染色法不易着色，墨汁负染，胞内有较大的反光颗粒。出芽繁殖，不形成假菌丝（酵母型菌落）培养特性：沙保或血琼脂培养基，2537生化特性：分解尿素荚膜多糖抗原：AD和AD5个血清型，我国约70%属A型,55,56,致病性,外源性感染，肺是主要入侵途径，也属于人体正常菌群，引起条件性感染原发感染通常在肺部，多数症状不明显，自愈；有的引起支气管肺炎；严重者呈暴发性感染并迅速死亡部分患者经血行传播至中枢神经及其它组织，引起肉芽肿性炎症，主要导致慢性脑膜炎致病物质：荚膜,57,微生物学检查,负染色镜检抗原检查：检查患者血清和脑脊液中新隐荚膜抗原分离鉴定尿素酶或酚氧化酶动物试验：小鼠,58,曲霉Aspergillus烟曲霉支气管哮喘或肺部感染毛霉Mucor腐生菌脑、肺、胃肠道卡氏肺孢菌Pneumocystiscarinii免疫缺陷病人肺炎,59,Aspergillus,Aspergillusisafilamentous,cosmopolitanandubiquitousfungusfoundinnature.Itiscommonlyisolatedfromsoil,plantdebris,andindoorairenvironment.ItisthesecondmostcommonlyrecoveredfungusinopportunisticmycosesfollowingCandida.,60,morphology,ItisafilamentousfungiHyphaeareseptateandhyaline.ConsistingofaVesicleThemorphologyandcoloroftheconidiophorevaryfromonespeciestoanother.,61,62,Aspergillusflavus,Aspergillusniger,Aspergillusfumigatus,63,足细胞分生孢子梗顶囊杆状小梗串状分生孢子（分生孢子头）,64,Species,ThegenusAspergillusincludesover185species.Around20specieshavesofarbeenreportedascausativeagentsofopportunisticinfectionsinman.Amongthese,Aspergillusfumigatusisthemostcommonlyisolatedspecies,followedbyAspergillusflavusandAspergillusniger.,65,PathogenicityandClinicalSignificance,局限性肺曲霉病基础疾病致肺空洞存在曲霉在此生长，不侵犯组织不播散曲霉肺炎（免疫功能低下）过敏性支气管肺曲霉病（过敏体质）,66,PathogenicityandClinicalSignificance,全身性曲霉病多发生在某些重症疾病晚期原发病灶主要在肺常由败血症引起全身性感染生前很难得到确诊,67,PathogenicityandClinicalSignificance,黄曲霉毒素与恶性肿瘤，尤其是肝癌的发生密切相关,68,Laboratorydiagnosis,Thespecimenlikesputumbiopsy,bronchalveolarlavageortransbronchialbiopsydependinginthesiteinvolved.Directexaminationofseptatehyphaeby10%KOHpreparation.血清学诊断或血清学试验检出曲霉细胞壁半乳糖甘露乳糖抗原.,69,Culture:InSDAwithantibioticsat25and37c有隔菌丝和分生孢子头.,70,PneumocystiscariniiPneumonia,71,PCP:HistoricalFeatures,1909-FirstrecognizedinlungsofGuineapigsbyChagas.SimilartoTrypanosomacruzi,yetdifferent.TheseobservationswereconfirmedbyCarinisoonafter.1912-Delanoesnameditafteritsdiscovererandtoreflectitstendencytoinfectthelungs.,72,PCP:HistoricalFeatures,Notinitiallybelievedtoaffecthumans.1951-VanekdescribedaninterstitialpneumoniawithPneumocystiscariniiorganismsinahuman.1955-Firstreportedinimmunodeficiency.1957-Firstassociatedwithchemotherapy.1982-AIDSandPneumocystiscariniiassociation.,73,PCP:ClassificationFungusorProtozoan?,Sharesbothfungalandprotozoannucleicacidsandstructuralfeaturesofeach.Doesnotgrowinfungalcultures,andantifungaltherapyisineffective.Foundtorespondtoanti-parasitictherapy.Initially,thoughttobeaProtozoan.Nowbelievedtobeafungus,probablyrelatedtoSaccharomyces.,74,卡氏肺孢菌Pneumocystiscarinii,生物学性状单细胞型，兼具原虫及酵母菌的特点，其发育过程如下：孢子小滋养体大滋养体（二分裂、出芽或接合生殖）囊前期孢子囊囊内减数分裂形成孢子成熟孢子囊内含8个孢子致病性艾滋病患者最常见的并发症和主要的致死原因微生物学检查采集痰液，染色镜检，若发现滋养体或孢子囊可确诊防治本菌对多种抗真菌药物不敏感，用药首选复方新诺明,75,X-rayofPneumocystisjiroveciipneumonia,Thereisincreasedopacification(whiteness)inthelowerlung