醫(yī)學(xué)微生物學(xué)課件

埃希菌屬

Escherichia形態(tài)染色0.4-0.7μm

1-3μm

短桿菌革蘭染色陰性有鞭毛有菌毛培養(yǎng)特性與生化反應(yīng)兼性厭氧營養(yǎng)要求不高生化反應(yīng)活潑，發(fā)酵多種糖類絕大多數(shù)發(fā)酵乳糖吲哚、甲基紅、VP、枸櫞酸鹽（IMViC）試驗(yàn)結(jié)果為++--抗原結(jié)構(gòu)O抗原：菌體抗原，170多種H抗原：鞭毛抗原，56種以上K抗原：莢膜抗原，100種以上O111：K58：H2致病物質(zhì)

菌毛、定居因子抗原粘附在腸道及尿道粘膜上皮細(xì)胞K抗原

與侵襲力有關(guān)抗吞噬與抗補(bǔ)體的溶菌作用

外毒素

腸毒素及溶血毒素；內(nèi)毒素與感染特征和嚴(yán)重程度有關(guān)；

所致疾病腸道外感染

泌尿道感染最多見

化膿性感染機(jī)體抵抗力降低、外傷如燒傷感染、膽囊炎、腹膜炎、腦膜炎及敗血癥等腹瀉引起腹瀉的大腸埃希菌腸產(chǎn)毒素型大腸埃希菌enterotoxigenicE.coli

ETEC腸侵襲型大腸埃希菌enteroinvasiveE.coli

EIEC腸致病型大腸埃希菌enteropathogenicE.coli

EPEC腸出血型大腸埃希菌enterohemorrhagicE.coli

EHEC腸集聚型大腸埃希菌enteroaggregativeE.coli

EAggEC腸產(chǎn)毒素型大腸埃希菌（ETEC）致病物質(zhì)腸毒素菌毛粘附素內(nèi)毒素K抗原所致疾病5歲以下嬰幼兒腹瀉旅游者腹瀉水樣便，惡心、嘔吐，腹痛，低熱腸侵襲型大腸埃希菌（EIEC）

致病物質(zhì)不產(chǎn)生腸毒素侵襲結(jié)腸粘膜上皮細(xì)胞并在其中生長繁殖所致疾病主要侵犯較大兒童和成人腹瀉呈膿血便，有里急后重致病類似菌痢，較少見診斷EIEC無動(dòng)力、生化反應(yīng)和抗原結(jié)構(gòu)腸致病型大腸埃希菌（EPEC）致病物質(zhì)不產(chǎn)生腸毒素及其他外毒素?zé)o侵襲力所致疾病嬰幼兒腹瀉腸出血型大腸埃希菌（EHEC）亦稱為vero毒素大腸埃希菌致病物質(zhì)菌毛：粘附作用毒素：vero毒素所致疾病出血性結(jié)腸炎溶血性尿毒綜合征腸集聚型大腸埃希菌（EAggEC）

致病物質(zhì)毒素：腸集聚耐熱毒素（EAST）粘附素所致疾病引起嬰兒持續(xù)性腹瀉，脫水，偶有血便

引起腹瀉的大腸埃希菌

菌株作用部位疾病與癥狀致病機(jī)制ETEC小腸旅行者腹瀉；嬰幼兒腹瀉；水樣便，惡心，嘔吐，腹痛，低熱質(zhì)粒介導(dǎo)LT和（或）ST腸毒素，大量分泌液體和電解質(zhì)EIEC大腸水樣便，繼以少量血便，腹痛，發(fā)熱質(zhì)粒介導(dǎo)侵襲和破壞結(jié)腸粘膜上皮細(xì)胞28ac、29、112ac、1244、152、164、167EPEC小腸嬰兒腹瀉；水樣便，惡心，嘔吐，發(fā)熱質(zhì)粒介導(dǎo)粘附和破壞上皮細(xì)胞2、55、86、111、114、119、125、126、127、128、142、158EHEC大腸水樣便，繼以大量出血，劇烈腹痛，低熱或無，可并發(fā)HUS、血小板減少性紫癜溶原性噬菌體編碼SLT-I或SLT-II，中斷蛋白質(zhì)合成157、26、111EAggEC小腸嬰兒腹瀉；持續(xù)性水樣便，嘔吐，脫水，低熱質(zhì)粒介導(dǎo)集聚性粘附上皮細(xì)胞，阻止液體吸收并產(chǎn)生毒素42、44、3、86等常見O血清型6、8、15、25、27、78、148、159

微生物學(xué)檢查法臨床標(biāo)本的檢查標(biāo)本

分離培養(yǎng)與鑒定腸道外感染涂片染色檢查分離培養(yǎng)鑒定腸道內(nèi)感染

ETECEIECEPECEHECEAggEC

衛(wèi)生細(xì)菌學(xué)檢查大腸菌群指數(shù)每1000毫升樣品中的

大腸菌群近似數(shù)細(xì)菌總數(shù)大腸菌群：指在37℃，24小時(shí)內(nèi)發(fā)酵乳糖產(chǎn)酸產(chǎn)氣需氧和兼性厭氧的腸道桿菌，包括埃希菌屬、枸櫞酸桿菌屬、克雷伯菌屬及腸桿菌屬等。

形態(tài)與染色G+細(xì)長彎曲,常一端或兩端膨大呈棒狀用美藍(lán)或奈瑟染色菌體兩端或一端可見著色較深的異染顆粒，有鑒定意義培養(yǎng)特性和生化反應(yīng)

需氧或兼性厭氧呂氏培養(yǎng)基亞碲酸鉀（K2TeO2·3H2O）血瓊脂平板變異形態(tài)、菌落和毒力S型變?yōu)镽型抵抗力較其他無芽孢細(xì)菌強(qiáng)對青霉素及廣譜抗生素敏感，對磺胺不敏感致病物質(zhì)白喉毒素（diphtheriatoxin）毒性強(qiáng)、具有高度抗原性的蛋白質(zhì)由A、B兩個(gè)肽鏈經(jīng)二硫鍵連接組成阻斷宿主細(xì)胞蛋白質(zhì)合成索狀因子（cordfactor）K抗原

所致疾病---白喉白喉棒狀桿菌（鼻咽腔）飛沫污染物品鼻咽喉氣管局部細(xì)菌和毒素的作用灰白色假膜（滲出的纖維素和白細(xì)胞及壞死組織凝固在一起）粘膜水腫及假膜脫落，引起呼吸道阻塞，甚至窒息死亡。外毒素入血毒血癥心肌肝腎上腺外周神經(jīng)內(nèi)臟出血心肌炎軟腭麻痹聲嘶

腎上腺功能障礙（2－7d潛伏期）抗毒素免疫錫克試驗(yàn)（Schicktest）錫克試驗(yàn)的原理是毒素和抗毒素的中和試驗(yàn)

免疫性微生物學(xué)檢查法標(biāo)本用棉拭子從患者病變部位假膜邊緣取材直接涂片鏡檢直接涂片，用美藍(lán)、革蘭染色法或奈瑟染色法染色鏡檢分離培養(yǎng)呂氏血清斜面毒力試驗(yàn)豚鼠試驗(yàn)瓊脂平板毒力試驗(yàn)形態(tài)與染色

革蘭陰性小桿菌無鞭毛，不形成芽胞，光滑型菌株有微莢膜。培養(yǎng)特性

專性需氧營養(yǎng)要求復(fù)雜，生長緩慢生化反應(yīng)

分解葡萄糖，產(chǎn)生少量酸。過氧化氫酶陽性，氧化酶陽性大多能分解尿素，能產(chǎn)生H2S致病性易感者人和動(dòng)物傳染源牛、羊、豬是本菌的主要自然宿主傳播途徑直接接觸和間接接觸致病物質(zhì)內(nèi)毒素、透明質(zhì)酸酶、莢膜所致疾病母畜流產(chǎn)波浪熱

分泌物、乳品消化道、呼吸道粘膜、皮膚及眼結(jié)膜人菌血癥1－6W潛伏期（70％）發(fā)熱、出汗、關(guān)節(jié)痛和全身乏力內(nèi)毒素的作用進(jìn)入肝、脾、骨髓（發(fā)熱也漸消退）繁殖入血菌血癥（體溫再次上升）波浪熱問題腸道病毒有哪些？是不是腸道感染的所有病毒都稱為腸道病毒？簡要說明腸道病毒的特性脊髓灰質(zhì)炎病毒的傳播途徑、致病機(jī)制是什么？如何預(yù)防脊灰？B組柯薩奇病毒的致病有何特點(diǎn)？ECHO病毒、輪狀病毒、杯狀病毒、小圓結(jié)構(gòu)病毒分別與哪些疾病有關(guān)？GroupsandSerotypesPicornaviridae（小RNA病毒科）Atleast71serotypes,dividedinto4subgroupsPolioviruses（脊髓灰質(zhì)炎病毒）Coxsackieviruses（柯薩奇病毒）Echoviruses（?？刹《荆㎞ewenteroviruses（新腸道病毒）morerecently,newenterovirusessubtypehavebeenallocatedsequentialnumbers(68-71))EnterovirusesSerotypesMorphology27nm,icosahedralsymmetry,noenvelopeSurfacecleft–attachmenttocellularreceptors:

Immunoglobulinsuperfamily,integrins,ICAM-1Enterovirusstructure腸道病毒的特點(diǎn)小球形病毒（~30nm），無包膜核酸為+ssRNA，有感染性衣殼有VP1—VP4四種蛋白，VP1—VP3分布在表面，VP4與內(nèi)部RNA結(jié)合耐酸耐乙醚，但鼻病毒除外在胞漿增殖，有明顯CPE，破胞釋放引起多種疾?。郝楸孕约膊　o菌性腦膜炎、心肌損傷、腹瀉、皮疹等Poliovirus-脊髓灰質(zhì)炎病毒Polioviruswasfirstidentifiedin1909byinoculationofspecimensintomonkeys.Theviruswasfirstgrownincellculturein1949whichbecamethebasisforvaccines中和試驗(yàn)可分3個(gè)血清型，3型間有部分共同抗原核酸有36-52%同源性人類是唯一的易感宿主在猴腎、人胚腎等細(xì)胞可增殖，表現(xiàn)為細(xì)胞變圓、壞死、脫落等典型溶細(xì)胞CPE在猴、猩猩等靈長類動(dòng)物敏感，在神經(jīng)系統(tǒng)感染，導(dǎo)致肢體麻痹TransmissionFecal–oralroute(糞－口途徑) viahandsandobjects

viafoodandwaterPerhapsthefirstwrittenrecordofavirusinfectionconsistsofaheiroglyphfromMemphis,drawninapproximately1400BC,whichdepictsatemplepriestcalledSiptahshowingtypicalclinicalsignsofparalyticpoliomyelitisFranklinD.RooseveltBornin1882atHydePark,NewYork--nowanationalhistoricsite--heattendedHarvardUniversityandColumbiaLawSchool.OnSt.Patrick'sDay,1905,hemarriedEleanorRoosevelt.Followingtheexampleofhisfifthcousin,PresidentTheodoreRoosevelt,whomhegreatlyadmired,FranklinD.Rooseveltenteredpublicservicethroughpolitics,butasaDemocrat.HewonelectiontotheNewYorkSenatein1910.PresidentWilsonappointedhimAssistantSecretaryoftheNavy,andhewastheDemocraticnomineeforVicePresidentin1920.Inthesummerof1921,whenhewas39,disasterhit-hewasstrickenwithpoliomyelitis.Demonstratingindomitablecourage,hefoughttoregaintheuseofhislegs,particularlythroughswimming.Atthe1924DemocraticConventionhedramaticallyappearedoncrutchestonominateAlfredE.Smithas"theHappyWarrior."In1928RooseveltbecameGovernorofNewYork.HewaselectedPresidentinNovember1932,tothefirstoffourterms.manifestationsMostinfectionsasymptomatic,95%Abortivepolio(minorillness),5%:fever,malaise,sorethroat, myalgia,headache)Asepticmeningitis(nonparalyticpolio),1%Paralyticpolio(majorillness),0.1%:

asymetricflaccidparalysis/ paresis.Lower,orupperextremities,thoracic,abdominal,bulbar. Involvement:spinalcordanteriorhorncells,motorcortex,dorsal rootganglia neurologicsequela(2/3)Post-poliosyndrome:progressiveatrophyyearslater免疫性脊灰病毒感染后可建立牢固特異免疫以體液免疫為主，在腸道局部產(chǎn)生sIgA，阻止病毒入血。血液中出現(xiàn)中和性IgG、IgM抗體，阻止病毒進(jìn)入神經(jīng)系統(tǒng)。中和抗體可長時(shí)間維持（終生）3型間有部分共同抗原，可以有極弱的交叉保護(hù)LaboratoryDiagnosisVirusIsolationMainstayofdiagnosisofpoliovirusinfectionpolioviruscanbereadilyisolatedfromthroatswabs,faeces,andrectalswabs,butrarelyfromtheCSFCanbereadilygrownandidentifiedincellcultureRequiresmoleculartechniques

todifferentiatebetweenthewildtypeandthevaccinetypeSerologyVeryrarelyusedfordiagnosissincecellcultureisefficient.Occasionallyusedforimmunestatusscreeningforimmunocompromisedindividuals預(yù)防原則隔離病人消毒排泄物、飲食衛(wèi)生、保護(hù)水源流行期不宜做小兒扁挑體摘除手術(shù)和其他疫苗接種疫苗接種：最好的手段被動(dòng)免疫：易感者用丙種球蛋白VaccinesAvailableIntramuscularPoliovirusVaccine(IPV)consistsofformalininactivatedvirusofall3poliovirusserotypes(Salk)

Producesserumantibodiesonly:doesnotinducelocalimmunityandthuswillnotpreventlocalinfectionofthegutHowever,itwillpreventparalyticpoliomyelitissinceviraemiaisessentialforthepathogenesisofthediseaseOralPoliovirusVaccine(OPV)Consistsofliveattenuatedvirusofall3serotypes(Sabin).ProduceslocalimmunitythroughtheinductionofanIgAresponseaswellassystemicimmunityRarelycausesparalyticpoliomyelitis,around1in3milliondosesMostcountriesuseOPVbecauseofitsabilitytoinducelocalimmunityandalsoitismuchcheapertoproducethanIPVThenormalresponseratetoOPViscloseto100%.OPVisusedfortheWHOpolioviruseradicationcampaignBecauseoftheslightriskofparalyticpoliomyelitis,someScandinaviancountrieshaverevertedtousingIPV.Becauseofthelackoflocalimmunity,smallcommunityoutbreaksofpoliovirusinfectionshavebeenreportedCurrentStatusofWildPoliovirusTransmission我國政府規(guī)定每年12月5日和1月5日為脊灰疫苗日?？滤_奇病毒（Coxsackievirus）從1948年美國紐約州Coxsackie鎮(zhèn)一名疑似脊髓灰質(zhì)炎的患兒糞便中用乳鼠接種的方法分離發(fā)現(xiàn)Coxsackieviruses-In1948,anewgroupofagentswereidentifiedbyinoculationintonewbornmicefromtwochildrenwithparalyticdisease.TheseagentswerenamedcoxsackievirusesafterthetowninNewYorkState.CoxsackievirusesAandBwereidentifiedonthebasisofthehistopathologicalchangestheyproducedinNewbornmiceandtheircapacitytogrowincellculturesCoxsackievirusesaredistinguishedfromotherenterovirusesbytheirpathogenicityforsuckling

ratherthanadultmice.Theyaredividedinto2groupsonthebasisofthelesionsobservedinsucklingmice.

GroupAviruses

(23types)produceadiffusemyositiswithacuteinflammationandnecrosisoffibersofvoluntarymuscles.GroupBviruses(6types)producefocalareasofdegenerationinthebrain,necrosisintheskeletalmuscles,andinflammatorychangesinthedorsalfatpads,thepancreasandoccasionallythemyocardium.

Inaddition,allfromgroupBandonefromgroupA(A9)shareagroupAg.Cross-reactivitieshavealsobeendemonstratedbetweenseveralgroupAvirusesbutnocommongroupantigenhasbeenfound.PathogenesisFecal-OralroutetrasmissionSpreadinthebodylikepoliovirusesDiseaseAssociationsParalyticDisease-mostcommonlyassociatedwithpoliovirusesbutotherenterovirusesmayalsoberesponsible,notablyenterovirus71Meningitis-causedbyallgroupsofenteroviruses,mostcommonlyseeninchildrenunder5yearsofage.Encephalitis-focalorgeneralizedencephalitismayaccompanymeningitis.Mostpatientsrecovercompletelywithnoneurologicaldeficit.Undifferentiatedfebrileillness-maybeseenwithallgroupsofenteroviruses.Handfootmouthdisease-usuallycausedbygroupAcoxsackievirusesalthoughgroupBcoxsackievirusesandotherenteroviruseshavebeencausedoutbreaks.Herpangina-causedbygroupAcoxsackieviruses.EpidemicPleurodynia(Bornholmdisease)-normallycausedbygroupBcoxsackieviruses.Myocarditis-groupBcoxsackievirusesarethemajorcauseofmyocarditis,althoughitmaybecausedbyotherenteroviruses.Itmaypresentinneonatesaspartofneonatalinfectionandisoftenfatal.Inadults,thediseaseisrarelyfatal.RespiratoryInfections-severalenterovirusesareassociatedwiththecommoncold.Rubelliformrashes

-arashdiseaseresemblingrubellamaybeseenwithseveralcoxsackieA,B,andechoviruses.NeonatalInfection-somecoxsackieBvirusesandechovirusesmaycauseinfectioninnewborninfants.Thevirusisusuallytransmittedperinatallyduringthebirthprocessandsymptomsvaryfromamildfebrileillnesstoaseverefulminatingmultisystemdiseaseanddeath.Conjunctivitis-associatedwithseveraltypesofenteroviruses,notablyCoxsackieA24andEnterovirus70(haemorrhagicconjunctivitis)Pancreatitis/Diabetes-associatedwithCoxsackieBvirusinfection.Theextentoftheroleofthevirusindiabetesisunknown.Exanthems-

Rubelliformrashes

-EVleadingcauseinsummer&fall.Alltypesofrash

Hand-foot-and-mouthdiseaseHand-foot-and-mouthdisease:mostlycoxackieAfever,malaise,sorethroat,vesiclesonbucalmucosa,tongue,hands,feet,buttockshighlyinfectiousresolution–1wHerpanginaHerpangina–usuallycoxackieAacuteonset,fever,sorethroat,dysphagialesions–posteriorpharynxcanpersistw’snogingivitisLaboratoryDiagnosisVirusIsolationMainstayofdiagnosisofenterovirusinfectionCoxsackieBandEchovirusescanbereadilygrownincellculturefromthroatswabs,faeces,andrectalswabs.TheycanalsobeisolatedfromtheCSFCoxsackieAvirusescannotbeeasilyisolatedincellculture.Theycanbeisolatedreadilyinsucklingmicebutthisisnotofferedbymostdiagnosticlaboratoriesbecauseofpracticalconsiderations.Moleculartechniquesmayprovideabetteralternative.SerologyVeryrarelyusedfordiagnosissincecellcultureisefficient.NeutralizationtestsorEIAsareusedbutareverycumbersomeandthusnotofferedbymostdiagnosticlaboratoriesManagementandPreventionThereisnospecificantiviraltherapyavailableagainstenterovirusesotherthanpolio.SomeauthoritiesuseIVIGinthetreatmentofneonatalinfectionsorsevereinfectionsinimmunocompromisedindividuals.However,theefficacyisuncertain.HNIGhavebeentopreventoutbreaksofneonatalinfectionwithgoodresults.Thereisnovaccineavailablemainlybecauseofthemultiplicityofserotypes.Thereislittleinterestindevelopingavaccineexceptagainstenterovirus71andcoxsackieBviruses.EchovirusesThefirstechoviruseswereaccidentallydiscoveredin1951fromhumanfaeces,unassociatedwithhumandiseaseduringepidemiologicalstudiesofpolioviruses.Theviruseswerenamedechoviruses(enteric,cytopathic,human,orphanviruses).TheseviruseswereproducedCPEincellcultures,butdidnotinducedetectablepathologicallesionsinsucklingmice.TypesAltogether,Thereare32echoviruses(types1-34;echovirus10and28werefoundtobeothervirusesandthusthenumbersareunused)ThereisnogroupechovirusAgbutheterotypiccross-reactionsoccurbetweenafewpairs.Pathogenesis致病性與柯薩奇病毒類似，呈多樣性。主要是無菌性腦炎、類脊髓灰質(zhì)炎等感染后對同型病毒可產(chǎn)生持久免疫診斷困難，對可疑患者可采糞便、CSF等標(biāo)本做病毒分離和中和試驗(yàn)尚無疫苗。預(yù)防以隔離為主NewEnterovirusesNewlyidentifiedpicornavirusesthatarenotpoliovirusesarenolongerclassifiedseparatedintothespeciescoxsackieandechovirusbecauseoftheambiguitiespresentedbyoverlappinghostrangevariations.4newenteroviruseshavebeenidentified(68-72).Enterovirus70isthecausativeagentepidemicsofacutehaemorrhagicconjunctivitisthatsweptthroughAfrica,Asia,IndiaandEuropefrom1969to1974.Thevirusisoccasionallyneurovirulent.Enterovirus71appearstobehighlypathogenicandhasbeenassociatedwithepidemicsofavarietyofacutediseases,includingasepticmeningitis,encephalitis,paralyticpoliomyelitis-likediseaseandhand-foot-mouthdisease.Enterovirus72wasoriginallyassignedtohepatitisAvirus,butithadnowbeenassignedtoanewfamilycalledheptoviruses.HaemorrhagicFeverwithRenalSyndrome(HFRS:laterrenamedhantavirusdisease,HVD)firstrecognizedinHeilongjiang,Chinainthe1930s,andcametotheattentionoftheWestduringtheKoreanwarwhenover3000UNtroopswereafflictedIttranspiredthatthediseasewasnotnewandhadbeendescribedbythe

Chinese1000yearsearlierIn1974,thecausativewasisolatedfromtheKoreanStrippedfieldmiceandwascalledHantaanvirusIn1995,anewdiseaseentitycalledhantaviruspulmonarysyndromewasdescribedinthe“fourcorners”regionoftheU.S.病毒體VirionFormsaseparategenusintheBunyavirusfamily

布尼雅病毒科Unlikeotherbunyaviridae,itstransmissiondoesnot

involvean

arthropodvectorEnveloped-ssRNAvirusVirions98nmindiameterwithacharacteristicsquaregrid-likestructure.GenomeconsistsofthreeRNAsegments:L,M,andS.基于中和試驗(yàn)的血清型

SubtypesofHantavirusesBasedNT黑線姬鼠型褐家鼠型歐洲棕背鼠型草原田鼠型巴爾干姬鼠型小家鼠型根據(jù)抗原和基因結(jié)構(gòu)分型（10型）Hantaan（漢灘型）Porrogiaandrelatedviruses-ThisgroupisfoundinChina,EasternUSSR,andsomepartsofS.Europe.Itisresponsibleforthesevereclassicaltypeofhantavirusdisease.Itiscarriedbystrippedfieldmice.(Apodemusagrarius)

Seoultype（漢城型）associatedwithmoderatehantavirusdisease.Itiscarriedbyratsandhaveaworldwidedistribution.IthasbeenidentifiedinChina,Japan,WesternUSSR,USAandS.America.Puumalatype

mainlyfoundinScandinaviancountries,France,UKandtheWesternUSSR.Itiscarriedbybankvoles(Clethrionomys

glareolus)andcausesmildhantavirusdisease(nephropathiaepidemica).SinNombre（辛諾柏型）foundinmanypartsoftheUS,CanadaandMexico.CarriedbytheDeerMouse(Peromyscusmaniculatus)

andcauseshantaviruspulmonarysyndrome.流行病毒學(xué)EpidemiologyNaturalhost:RodentApodemusagrarius(Strippedfieldmice,黑線姬鼠)傳染源：黑線姬鼠、褐家鼠、大林姬鼠Viralcontaminationcomesfromrodenturine,stool,salivarysecretionSeasonalandregionaldistribution(autumnandwinter,Oct.-Jan.)Theinfectionrouteisstilluncertain.Thepossibleentriesarerespiratorytract,mouth,anddirectcontactRodentCarriersofHantavirusesStrippedfieldmouse(Apodemusagrarius)

Bankvole(Clethrionomysglareolus)

DeerMouse(Peromyscusmaniculatus)

Rat(Rattus)臨床特點(diǎn)ClinicalFeaturesIncubation:2weeks,HFRSPathogenesismechanismisunknown.Immunologicalreactionmayplayrole極低的隱性感染率Verylowsubclinicalinfectionrate(1-4%)

病后穩(wěn)定的免疫力，一般不再發(fā)病Stablehumoralimmunity.norepeatinfection致病性PathogenesisThemultisystempathologyofHVDischaracterizedbydamagetocapillariesandsmallvesselwalls,resultinginvasodilationandcongestionwithhemorrhagesClassically,hantavirusdiseaseconsistsof5distinctphases.ThesephasesmaybeblurredinmoderateormildcasesFebrilephase

發(fā)熱期abruptonsetofasevereflu-likeillnesswithaerythematousrashafteranincubationperiodof2-3daysHypotensivephase

低血壓期beginsatday5ofillnessOliguricphase

少尿期beginsatday9ofillness.Thepatientmaydevelopacuterenalfailureandshock.Haemorrhagesareusuallyconfinedtopetechiae.ThemajorityofdeathsoccurduringthehypotensiveandoliguricphasesDiureticphase

多尿期occursbetweendays12-14Convalescentphase

恢復(fù)期mayrequireupto4monthsComparativeClinicalFeaturesofRecognizedHantavirusDisease(HVD)漢坦病毒肺綜合征

HantavirusPulmonarySyndromeThemajorityofcasesarecausedbytheSinNombrevirus（漢坦病毒屬辛諾柏病毒）Morethan250casesofHPShavebeenreportedthroughoutNorthandSouthAmericawithamortalityrateof50%HPShasasimilarfebrilephase,However,thedamagetothecapillariesoccurpredominantlyinthelungsratherthanthekidney.Shockandcardiaccomplicationsmayleadtodeath

診斷Diagnosis血清學(xué)診斷-avarietyoftestsincludingIF,HAI,SRH,ELISAshavebeendevelopedforthediagnosisofHVDandHPS直接檢測病毒抗原-thisappearstobemoresensitivethanserologytestsintheearlydiagnosisofthedisease.ThevirusantigencanbedemonstratedinthebloodorurineRT-PCR

-foundtoofgreatuseindiagnosinghantaviruspulmonarysyndrome病毒分離Virusisolation-isolationofthevirusfromurineissuccessfulearlyinhantavirusdisease.Isolationofthevirusfromthebloodislessconsistent免疫組化

-usefulindiagnosingHPS治療和預(yù)防TreatmentofHVDandHPSdependsmainlyonsupportivemeasures

支持療法Ribavirin

利巴韋林reportedtobeusefulifgivenearlyinthecourseofhantavirusdiseaseVaccinationaninactivatedvaccineisbeingtriedoutinChina.OthercandidatevaccinesarebeingpreparedRodentControlcontrolmeasuresshouldbeaimedatreducingcontactbetweenhumansandrodents新疆出血熱病毒

XinjiangHemorrhagicFeverVirus于1966年首次從我國新疆塔里木盆地出血熱病人血液、尸體臟器及硬蜱中分離成功而得名該病毒在流行病學(xué)及病毒抗原性等方面與克里米亞-剛果出血熱病毒（Crimean-Congohemorrhagichevervirus，CCHFV）相似，故認(rèn)為XHFV與CCHFV是同一種病毒，屬布尼雅病毒科（Bunyaviridae）內(nèi)羅病毒屬（nairovirus）

生物學(xué)性狀球形或橢圓形，直徑為90nm～120nm，外有包膜，表面有空管樣突起病毒基因組為分節(jié)段的-ssRNA，包括L、M及S節(jié)段，與病毒的核蛋白（C）及少量病毒多聚酶共同組成病毒核衣殼。病毒的核衣殼呈二十面體對稱出生后l～4天的乳鼠對XHFV最為敏感，常用于病毒分離及傳代。用VeroE6等細(xì)胞培養(yǎng)病毒不產(chǎn)生CPE，可用免疫熒光法通過檢測感染細(xì)胞的胞漿內(nèi)可形成嗜堿性包涵體致病性與免疫性新疆出血熱是一種主要發(fā)生于荒漠、牧場的自然疫源性疾病，有嚴(yán)格的地區(qū)性和明顯的季節(jié)性野生動(dòng)物（嚙齒類動(dòng)物）和家畜（羊、牛、馬、駱駝、狐貍和兔）是自然宿主和傳染源。羊在維持XHF疫原上起重要作用硬蜱特別是亞洲璃眼蜱（hyalommaasiaticum）是傳播媒介。病毒在蜱體內(nèi)增殖并經(jīng)卵傳給子代，蜱也是病毒的長期儲存宿主由于蜱在每年的4月～6月期間大量增殖，此時(shí)也是人群發(fā)病的高峰。當(dāng)人被帶毒蜱叮咬或與病畜直接接觸（通過破損皮膚）感染病毒侵入體內(nèi)后，經(jīng)5～7天潛伏期發(fā)病，臨床表現(xiàn)以發(fā)熱和出血為主要特征人感染該病毒后可以刺激機(jī)體產(chǎn)生中和（NT）抗體、補(bǔ)體結(jié)合（CF）抗體和血凝抑制（HI）抗體。其中NT抗體出現(xiàn)較早，維持較久。病后可獲得持久免疫力微生物學(xué)檢查法確診主要依賴于病毒的分離鑒定患者雙份血清中特異性抗體的檢查

防治原則防治措施主要包括防蜱咬和滅蜱嚴(yán)格隔離病人，并對病人血液、分泌物、排出物等要進(jìn)行消毒處理加強(qiáng)醫(yī)務(wù)人員的防護(hù)，避免直接接觸病人的血液等而被感染用乳鼠腦組織培養(yǎng)精制的病毒滅活疫苗具有一定的預(yù)防效果

埃博拉病毒非洲出血熱（Africahemorrhagicfever）主要包括埃博拉熱（Ebolafever）和馬堡熱（Marburgfever），分別由埃博拉病毒（Ebolavirus）和馬堡病毒（Marburgvirus）感染所致兩種病毒均為RNA病毒，同屬于絲狀病毒科（Filoviridae）的絲狀病毒屬（filovirus），形態(tài)結(jié)構(gòu)酷似，但抗原性明顯不同致病性非洲出血熱的主要臨床特點(diǎn)是高熱、皮膚瘀血、紫癜、鼻衄、消化道和泌尿生殖道出血、血小板減少以及明顯的全身中毒癥狀，常導(dǎo)致休克和死亡儲存宿主是嚙齒類動(dòng)物，經(jīng)密切接觸可以傳播給人人與人主要通過密切接觸及體液（尿或糞便）等的污染而傳播目前尚無特異性防治措施。主要采取維持腎功能和水電解質(zhì)平衡、積極控制出血和休克等支持療法進(jìn)行治療

一、放線菌屬革蘭陽性非抗酸性絲狀菌厭氧或微需氧硫磺樣顆粒屬正常菌群可引起內(nèi)源性感染第一節(jié)結(jié)核分枝桿菌流行病學(xué)全球總疫情20億人口感染了結(jié)核菌，現(xiàn)癥結(jié)核病人2000萬，每年新發(fā)病人數(shù)800－1000萬，每年300萬人死于結(jié)核病。我國疫情現(xiàn)有活動(dòng)性肺結(jié)核病人500萬人，傳染性肺結(jié)核病人200萬人，每年因結(jié)核病死亡25萬人?！笆澜绶乐谓Y(jié)核病日”－2004年控制結(jié)核讓每一次呼吸更健康2003年防治結(jié)核，造福人民2002年遏制結(jié)核，消除貧困2001年積極發(fā)現(xiàn)、治愈肺結(jié)核病人2000年動(dòng)員全社會(huì)共同關(guān)注結(jié)核病3月24日形態(tài)與染色

細(xì)長略彎，有時(shí)呈分枝狀（1～4）

m×0.4

m無芽胞、鞭毛和莢膜

齊-尼氏抗酸染色培養(yǎng)特性

專性需氧營養(yǎng)要求高－饞生長緩慢－懶羅氏固體培養(yǎng)基－丑抵抗力

對某些理化因素有較強(qiáng)的抵抗力抗干燥抗酸堿抗染料在干燥痰中可存活6－8個(gè)月變異性形態(tài)菌落耐藥性毒力卡介苗（BCG）：將有毒的牛型結(jié)核分枝桿菌培養(yǎng)于含甘油、膽汁、馬鈴薯的培養(yǎng)基中，經(jīng)230次移種傳代，歷時(shí)13年而獲得的減毒活菌株，目前廣泛用于人類結(jié)核病的預(yù)防。致病物質(zhì)類脂分枝菌酸索狀因子：抑制白細(xì)胞游走，引起肉芽腫。

磷脂：能刺激單核細(xì)胞增生，抑制蛋白酶的分解作用蠟質(zhì)D：能引起遲發(fā)型超敏反應(yīng)。硫酸腦苷酯：使結(jié)核分枝桿菌易于胞內(nèi)寄生。蛋白質(zhì)

產(chǎn)生遲發(fā)型超敏反應(yīng)，導(dǎo)致組織壞死和全身中毒癥狀，參與結(jié)核結(jié)節(jié)的形成。多糖所致疾病肺部感染原發(fā)感染繼發(fā)感染肺外感染

吞噬細(xì)胞內(nèi)繁殖（滲出性炎癥）原發(fā)性感染原發(fā)性感染見于學(xué)齡兒童及未受過感染的成人。結(jié)核分枝桿菌

肺泡吞噬細(xì)胞原發(fā)感染（primaryinfection）全身性粟粒性結(jié)核結(jié)核結(jié)節(jié)淋巴結(jié)病灶逐漸纖維化和鈣化所致疾病肺部感染原發(fā)感染繼發(fā)感染已痊愈的原發(fā)感染可以復(fù)活成為活動(dòng)性結(jié)核病。由外界新侵人的結(jié)核分枝桿菌引起。肺外感染

免疫性

結(jié)核的免疫為有菌免疫或稱傳染性免疫。細(xì)胞免疫在抗感染免疫中更重要。免疫反應(yīng)特點(diǎn)：產(chǎn)生細(xì)胞免疫的同時(shí)也產(chǎn)生遲發(fā)型超敏反應(yīng)。結(jié)核桿菌遲發(fā)型超敏反應(yīng)和免疫反應(yīng)是由不同細(xì)胞亞群細(xì)胞介導(dǎo)的兩個(gè)獨(dú)立反應(yīng)可發(fā)生在同一感染機(jī)體。結(jié)核菌素試驗(yàn)原理皮膚遲發(fā)型超敏反應(yīng)應(yīng)用判斷機(jī)體對結(jié)核分枝桿菌有無免疫力用于嬰幼兒結(jié)核病診斷腫瘤患者細(xì)胞免疫功能測定對未接種BCG的人群進(jìn)行流行病學(xué)調(diào)查結(jié)核菌素試劑舊結(jié)核菌素（oldtuberculin，OT）純蛋白衍生物（PPD）:PPD-C、BCG-PPD試驗(yàn)方法分別取兩種PPD5單位注入兩前臂皮內(nèi)，48～72小時(shí)后觀察。結(jié)果分析≥15mm為強(qiáng)陽性－－可能有活動(dòng)性結(jié)核病紅腫硬結(jié)超過5mm者為陽性PPD-C側(cè)>BCG-PPD側(cè)感染PPD-C側(cè)<BCG-PPD側(cè)卡介苗接種紅腫硬結(jié)小于5mm者為陰性反應(yīng)受試者處于原發(fā)感染的早期，T淋巴細(xì)胞尚未被致敏老年人患嚴(yán)重結(jié)核病或其他傳染?。ㄈ缏檎畹龋┑幕颊攉@得性免疫功能低下，如艾滋病患者或使用免疫抑制劑治療者微生物學(xué)檢查標(biāo)本痰、尿、糞、腦脊液及胸、腹水、血等涂片染色鏡檢培養(yǎng)法動(dòng)物試驗(yàn)細(xì)菌學(xué)基因診斷特異性防治卡介苗預(yù)防卡介苗是目前唯一可預(yù)防結(jié)核的疫苗。藥物治療鏈霉素、異煙肼、對氨基水楊酸、利福平、乙胺丁醇等。五項(xiàng)原則早期、聯(lián)合、規(guī)律、適量、全程

第二節(jié)麻風(fēng)分枝桿菌

（M.leprae）形態(tài)與染色

細(xì)長略彎曲抗酸染色陽性典型的胞內(nèi)寄生菌培養(yǎng)特性不能在人工培養(yǎng)基中生長犰狳抵抗力在干燥環(huán)境中7天以內(nèi)仍有繁殖能力致病性易感人群人傳播途徑直接接觸或由飛沫傳播潛伏期一般是6個(gè)月至5年發(fā)病慢、病程長麻風(fēng)瘤型麻風(fēng)結(jié)核樣型病人面部結(jié)節(jié)融合可呈“獅面”狀微生物學(xué)診斷

抗酸染色PCR技術(shù)防治原則

目前尚無有效的菌苗進(jìn)行特異的預(yù)防早期發(fā)現(xiàn)早期隔離治療氨苯砜、利福平和氯苯吩嗪問題肝炎病毒有哪些？簡述甲型肝炎病毒的傳播方式、致病特點(diǎn)和預(yù)防原則簡述乙型肝炎病毒的生物學(xué)性狀、抗原抗體組成及檢出的意義乙型肝炎病毒的傳播方式和致病特點(diǎn)及預(yù)防原則丙型肝炎病毒的生物學(xué)特點(diǎn)和致病特點(diǎn)丁型肝炎病毒（HDV）的概念簡述戊型肝炎病毒傳播方式和致病特點(diǎn)肝炎病毒（Hepatitisvirus）以侵害肝臟為主引起病毒性肝炎的病毒種類：甲型肝炎病毒（HAV）、乙型肝炎病毒（HBV）、丙型肝炎病毒（HCV）、丁型肝炎病毒（HDV）、戊型肝炎病毒（HEV）、GBV-C/HGV、TTV其他病毒如黃熱病毒、CMV、EBV、風(fēng)疹病毒等也可引起肝炎，但不列為肝炎病毒A“Infectious”“Serum”ViralhepatitisEntericallytransmittedParenterallytransmittedF,G,TTV?otherENANBBDCViralHepatitis-HistoricalPerspectivesHepatitisAvirus1973年Feinstone應(yīng)用免疫電鏡技術(shù)從急性肝炎患者糞便懸液中發(fā)現(xiàn)生物學(xué)性狀與腸道病毒一致，故1982年國際病毒命名委員會(huì)將它分類為小核糖核酸病毒科腸道病毒屬72型Anti-HAVPrevalenceHighIntermediateLowVeryLowGeographicDistributionofHAVinfection生物學(xué)性狀HAV為球形顆粒，直徑27～32nm，無包膜?；蚪M為線狀單正鏈RNA由VP1～4四種多肽組成，VP1是主要衣殼蛋白和中和抗原，能中和所有HAV細(xì)胞培養(yǎng)：HAV可用猴腎、人胚腎細(xì)胞等進(jìn)行增殖和傳代，但不引起CPE易感動(dòng)物有黑猩猩、南美洲猴、獼猴等，接種后可出現(xiàn)急性肝炎抵抗力：較強(qiáng)，對乙醚、酸、熱（60oC）穩(wěn)定。高壓、紫外、煮沸等可滅活致病性傳染源為患者和隱性感染者傳播方式是糞－口途徑。HAV污染食物、水源、海產(chǎn)品等引起暴發(fā)或散發(fā)流行隱性感染率高，成人HAV抗體陽性率高達(dá)70%—90%病毒進(jìn)入機(jī)體經(jīng)過兩次病毒血癥，到達(dá)肝臟，在肝細(xì)胞增殖致病非溶細(xì)胞型病毒，不直接殺傷細(xì)胞，患者癥狀高峰是潛伏期末和癥狀出現(xiàn)初期，與病毒復(fù)制高峰時(shí)間不相符，說明病毒復(fù)制量與癥狀嚴(yán)重程度不一致，故認(rèn)為免疫應(yīng)答參與損傷過程發(fā)病后期糞便中可檢出sIgA抗體。出現(xiàn)病毒的特異細(xì)胞免疫應(yīng)答典型的甲肝是自限過程，大約三個(gè)月，無慢性病例

Incubationperiod: Average30days Range15-50daysJaundiceby <6yrs,<10%

agegroup: 6-14yrs,40%-50%

>14yrs,70%-80%Complications: Fulminanthepatitis

Cholestatichepatitis

RelapsinghepatitisChronicsequelae: None

HepatitisA-ClinicalFeaturesFecalHAVSymptoms01234561224HepatitisAInfectionTotalanti-HAVTitreALTIgManti-HAVMonthsafterexposureTypicalSerologicalCourse

Closepersonalcontact

(e.g.,householdcontact,sexcontact,childdaycarecenters)Contaminatedfood,water

(e.g.,infectedfoodhandlers,rawshellfish)Bloodexposure(rare)

(e.g.,injectingdruguse,transfusion)

HepatitisAVirusTransmissionSourcesofHAVInfection

1983-93PercentageofCasesSource:CDC,ViralHepatitisSurveillanceProgramYearPersonalcontactDaycarecenterForeigntravelOutbreakDruguse40302010019831984198519861987198819891990199119921993ConcentrationofHAVinVariousBodyFluidsSource: ViralHepatitisandLiverDisease1984;9-22 JInfectDis1989;160:887-890FecesSerumSalivaUrine1001021041061081010InfectiousDosespermlAge-specificIncidenceofHepatitisA1983-93Source:CDC,NationalNotifiableDiseasesSurveillanceSystemYearReportedCases(per100,000)198319841985198619871988198919901991199219930510152025

5-14years

15-24years

25-39years

0-4years

40+yearsEndemicityDiseaseRatePeakAgeofInfectionTransmissionPatternsHighLowtoHighEarlychildhoodPersontoperson;outbreaksuncommonModerateHighLatechildhood/youngadultsPersontoperson;foodandwaterborneoutbreaksLowLowYoungadultsPersontoperson;foodandwaterborneoutbreaksVerylowVerylowAdultsTravelers;outbreaksuncommonGlobalPatternsofHepatitisAVirusTransmission診斷（LaboratoryDiagnosis）AcuteinfectionisdiagnosedbythedetectionofHAV-IgMinserumbyEIA.PastInfectioni.e.immunityisdeterminedbythedetectionofHAV-IgGbyEIA.

防治原則加強(qiáng)食品衛(wèi)生管理，水源保護(hù)。但HAV感染以隱性感染和無黃疸型病毒例占多數(shù)，故對傳染源較難控制我國已批準(zhǔn)將減毒疫苗株H2株和L1株投放市場試用應(yīng)急預(yù)防可用丙種球蛋白基因工程疫苗也正在研究之中Manycasesoccurincommunity-wideoutbreaksnoriskfactoridentifiedformostcaseshighestattackratesin5-14yearoldschildrenserveasreservoirofinfectionPersonsatincreasedriskofinfectiontravelershomosexualmeninjectingdrugusers

HepatitisAVaccinationStrategiesEpidemiologicConsiderations

Pre-exposuretravelerstointermediateandhighHAV-endemicregionsPost-exposure(within14days)RoutinehouseholdandotherintimatecontactsSelectedsituationsinstitutions(e.g.,daycarecenters)commonsourceexposure(e.g.,foodpreparedbyinfectedfoodhandler)HepatitisAPrevention-ImmuneGlobulinGroupAgeNo.DosesEL.U.*(ml)Schedule(months)Childrenandadolescents2-18years3360(0.5)0,1,6-12Adults>18years21,440(1.0)0,6-12DosesHAVRIXa*ELISAunitsRecommendedDoses&SchedulesofHAVVaccinationHapatitisBVirus1963年Blumberg在多次輸血的血友病患者中發(fā)現(xiàn)澳抗，1968年確與血清型肝炎高度相關(guān)，1970年Dane在電鏡下看到具有傳染性的42nm病毒顆粒HBV在亞洲廣泛流行，在中國約10%人口攜帶該病毒，全球約3.5億1983年將HBV及與其分子結(jié)構(gòu)、生物學(xué)特性相似的土撥鼠肝炎病毒(woodchuckhepatitisvirus,WHV)、地松鼠肝炎病毒(groundsquirrelhepatitisvirus,GSHV)及鴨肝炎病毒(duckhepatitsvirus,DHV)歸納起來獨(dú)立命名為嗜肝病毒科（Hepadnaviridae）HBsAgPrevalence38%-High2-7%-Intermediate<2%-LowGeographicDistributionofChronicHBVInfection形態(tài)與結(jié)構(gòu)電鏡檢查血清標(biāo)本可見小球形顆粒（22nm）、管形顆粒（22nmx50—700nm）、大球形顆粒（42nm）完整的HBV顆粒亦稱Dane顆粒，顆粒直徑為42nm具有雙層衣殼結(jié)構(gòu)。外殼相當(dāng)于包膜，由脂質(zhì)雙層和乙肝表面抗原（HBsAg）、多聚人血清白蛋白受體（PHSA-r）和前S抗原（Pre-S）組成。內(nèi)部有28nm的核心，表面相當(dāng)于內(nèi)衣殼，含有乙型肝炎核心抗原（HBcAg）和乙型肝炎e抗原（HBeAg）。內(nèi)部有HBV的DNA和DNA多聚酶HBV基因組DNA是由3.2KB的長鏈L（-）和短鏈S（+）（約為L鏈的50%至85%長）組成的不完全雙鏈環(huán)狀DNA，長鏈載有病毒蛋白質(zhì)的全部密碼，有4個(gè)開放讀碼框架(ORF)，分別稱為S、C、P和X區(qū)HBV:ReplicationHBV2.4KB3.5KBProvirusRTReplicateNucl