腺病毒感染

腺病毒感染 Vo1.6,No.4Apr,2006nfections9 interpretationcanbeproblematicbecauseviralDNAmaypersist forupto1yearafterinfection,eveninhealthyadults. Preventionofinfection Itispossiblethat,within10years,parvovirusB19infectionmay bepreventable.Candidaterecombinantvaccinesarebasedon emptyvirusparticles,whichhavegeneratedexcellentneutralizing antibodyresponsesinprimatemodels.Studiesoffamiliesinwhich anindexcasepresentswithacuteparvovirusinfectionindicatethat thepresenceofspecificIgGdirectedagainstparvovirusantigens correlateswithprotection.? REFERENCES 1CossartYE,FieldAM.CantBeta1.Parvovirus-Iikeparticlesinhuman sera.Lancet1975:i:72-3. 2RicePS.CohenB.InvestigationofaschooIoutbreakofparvovirus B19infectionusingsalivaryantibodyassays.EpidemialIn『fect1996; 116:331-3. 3BrownKE,AndersonSM,YoungNS.ErythrocytePantigen:cellular receptorforB19parvovirus.Science1993;262:114—17. 4PattisonJR,JonesSE,HodgsonJefaLParvovirusinfectionsand hypoplasticcrisisinsickle?celIanaemia.Lancet1981:i.664—5. 5MoudgiIA,ShidbanH.NastCCetaLParvovirusB19infection.related complicationsinrenaItransplantrecipients:treatmentwith intravenousimmunoglobulin.Transplantatian1997;64:1847—5O. 6MillerE,FairleyCK,CohenBJef口LImmediateandIong-term outcomeofhumanparvovirusB19infectioninpregnancy.BrJObstet Gynaecol1998;105:174-8. 7JensenIRThorsenP'JeuneBetaLAnepidemicofparvovirusB19in apopulationof3,596pregnantwomen:astudyofsOciOdemOgraphic andmedicaIriskfactors.BrJObstetGynaecaf2000;107:637—43. FU盯HERREADING AndersonLJ,YoungNS,eds.HumanparvovirusB19.ManagrViral 1997;20. BrownKE,YoungNS.ParvovirusB19inhumandisease.AnnuRevMed 1997;48:59-67. CohenB1.ParvovirusB19:anexpandingspectrumofdisease.8MJ 1995:311:1549-52. Humanparvovirusinfection.NEnglJMed1986;314:645-7. YoungNS.BrownKE.ParvovirusB19.NEnglJMed2004;350:586—97 Practicepoints AnimaIparvovirusesdonotinfecthumans ParvovirusB19infectionisresponsiblefora10%excessfetaI IOSSratewhenmaternaIinfectionoccursinthefirst20weeks ofgestation HospitaIandschooIoutbreaksaredifficulttocontro1. becausesecondarycasesarealreadyinfectiousatthetimeof notificationoftheindexcase Intrauterinebloodtransfusionshouldbeusedtotreat parvovirus-inducedhydropsfetalis MEDICINElNTERNATl0NAL Adenovirusinfections PhyllisFlomenberg AdenovirusesareubiquitousDNAvirusesthatarecommoncauses offebrileillnessinearlychildhood.Theyaremostoftenassociated withrespiratorytractdisease,butcanalsocause异astrOintestinal, ophthalmological,neurologicalandgenitourinarymanifestations. Althoughmostadenoviraldiseasesareself-limiting.fatalinvasive diseasemayoccurinimmunocompromisedpatientsandoccasion— allyinhealthychildrenandadults. Epidemiology Adenovirusinfectionsoccurworldwidethroughouttheyear.There aremorethan50differentadenovirusserotypes.classifiedintosix groups(A—F).GroupCserotypes1,2and5areprimarilyassociated withrespiratorydiseaseandarethosemostcommonlyisolated fromthegeneralpopulation.Transmissionoccursviaaerosolpar. ticles,thefaeco-oralrouteorcontaminatedfomites.Adenoviruses arenon—envelopedandsurviveforlongperiodsonsurfacesin theenvironment.Theyareresistanttolipiddisinfectants,butare inactivatedbyheat,formaldehydeandchlorine. AdenOvirusescause5-10%ofallfebrileillnessesininfants andyoungchildren.Mostindividualsexhibitserologicalevidence ofadenovirusinfectionbytheageof10years.Thevirusesare commoninhouseholdsandday—carecentres.andnosocomial transmissionhasbeendocumented.Adenovirusescausepersistent infections,andprolongedfaecalsheddingiscommon.Reactivation ofpersistentinfectionmayhavearoleinadenovirusdiseasein immunocompromisedpatients. Manyepidemicsofadenoviraljnfectionshavebeendescribed. including: .seriousoutbreaksofacuterespiratorydiseaseinmilitary recruits .pharyngoconjunctivalfeverinsummercampsandinassocia— tionwithpublicswimmingpoolsandlakes ?haemorrhagickeratoconjunctivitisinmedicalfacilities. ClinicaIfeatures Theclinicalmanifestationsofadenovirusdiseasevarywithage andthepresenceofimmunedysfunction(Figure1). Respiratorytract:adenovirusisthevirusmostcommonlyisolated fromyoungchildrenwithfebrilerespiratoryillness.Theusual durationofillnessis5-7days,butsymptomsmaypersistforup tO14days. PhyllisFlomenbergisInfectiousDiseaseConsultantatThomasle[ferson University,Philadelphia,USAConpictofinterests:nonedeclared. ?2OO6TheMedicinePubl~hingCompanyLtd 10 1 Diseasescausedbyadenoviruses Infants .Pharyngitis,corzya,pneumonia .Otitismedia .Diarrhoea ChiIdten .Upperrespiratorydisease,pneumonia .Pharyngoconjunctivalfever .Diarrhoea,mesentericadenitis .Haemorrhagiccystitis YoungaduIts .Acuterespiratorydisease Adults .Epidemickeratoconjunctivitis Immunocompromisedpatients .Pneumonia .Gastroenteritis,hepatitis .Haemorrhagiccystitis,nephritis .Meningoencephalitis Infections ?Primarydiagnosesarepharyngitis,coryzaandotitismedia. ?Itiscommontofindexudativetonsillitisandcervicaladeno— pathy,whichisclinicallyindistinguishablefromgroupAstrepto— coccaldisease. ?Feverandothersystemicmanifestationsfe.g.malaise,headache, myalgia,abdominalpain)arecommon. ?Pharyngitisiscommonlyassociatedwithconjunctivitis,laryngo— tracheitis,bronchitisorpneumonia.Lessoften,adenoviruscan causeapertussis—likesyndrome,bronchiolitis,coryzawithout fever,Orexanthem. Pnenmon/a—adenovirus(mostcommonlygroupBtypes3,7 and211causesabout10%ofcasesofpneumoniainchildren.The pneumoniaismoresevereininfantsthaninolderchildrenand maybeassociatedwithlethargy,diarrhoea,vomiffng,pharyngitis andconjunctivitis.Radiologyrevealsdiffuse,bilateralpulmonary infiltratessimilartothoseseeninotherviralpneumonias.Patho— logicalchangesincludenecrotizingbronchitis,bronchiolitis,and pneumoniawithmononuclearcelljnfiltration.hyalinemembranes andnecrosis.Extrapulmonarycomplicationsincludemeningo— encephalitis,hepatitis,myocarditis,nephritis,neutropeniaand disseminatedintravascularcoagulation.Inchildren.thereisahigh incidenceofpulmonarysequelae,particularlybronchiectasis. Eyes:groupBtypes3and7cancausebenignfollicularconjunc— tivitis,whichmayoccuraloneorwithpharyngitis(pharyngo— conjunctivalfever)..Epidemickeratoconiunctivitiscausesmore seriousdiseaseandisassociatedprimarilywithgroupDtypes8, 19and37;itischaracterizedbybilateralconjunctivitisassociated withpre—auricularadenopathy,followedbydevelopmentofpainful cornealopacitiesthatcancauseprolongedimpairedvision. Gastrointestinaltract:inyoungchildren.5-15%ofacutediar— rhoealillnessiscausedbytheentericgroupFadenovirustypes ?^t?_T11??11 Vo1.6.No.4 andoccasionallycausesintussusceptiOn.Hepatitisisacommon complicationofadenoviruspneumoniaininfants.Inpatientswho areimmunocompromised,adenoviruscancausegastroenteritis; hepatitismayalsooccur,causedparticularlybygroupCtype5. Genit0urinarvtract:adenovirusgroupBtypes11and21have beenassociatedwiththeuncommonsyndromeofhaemorrhagic cystitisinboys.Inadults.anoculogenitalsyndromecausedby adenovirustype19hasoccasionallybeendescribed.Inimmuno— compromisedpatients,adenovirusgroupBtypes11,34and35can causehaemorrhagiccystitis,withorwithoutnephritis. Nervoussystem:meningitisandencephalitishavebeenreported occasionallyinassociationwithadenovirusinfection.Neurological involvementmaybeaprimarymanifestationormaybefoundin associationwithseverepneumonia,particularlytype7. Viralcultureisasensitivemethodfordetectingadenovirus. Mostserotypescauseacharacteristiccytopathiceffectinhuman epithelialandfibroblastcell1inesafterafewdaystoweeks.Inthe morerapidshell—vialcultureassay,samplesarecentrifugeddirectly ontocellmonolayers.incubatedfor1—2days,andexaminedfor adenovirusproteinsbyimmunofluorescenceassay.Adenovirus maybeculturedfromthroat,nasopharynx,conjunctiva,sputum, urine,stool,CSF'bloodortissuespecimens.Howeve~theenteric adenovirusgroupFtypes40and41donotgrowinroutinecell lines.andpositivestoolculturesforotherserotypesmayrepresent asymptomaticfaecalshedding. Detectionofadenoviralantigensinclinicalsamplesbyenzyme— linkedimmunosorbentassay(ELISA)orimmunofluorescence assayislesssensitivethanviralculture,butmorerapid.ELISAis particularlyusefulforthefastidiousserotypes40and41. DetectionofadenoviralDNAbypolymerasechainreaction (PCR1analysisismoresensitiveandrapidthanviralculture. MonitoringbloodsamplesforadenoviralDNAbyquantitativePCR analysismaybeusefulforearlydetectionofadenovirusdiseasein haematopoieticstemcellrecipients.However,theseassaysrequire furtherclinicalvalidation. Hist0path0l0gV:adenovirusdiseasemaybeconfirmedbycharac— teristicintranuclearinclusionsintissuesections(Figure21.Cells developsmalleosinophilicinclusionssoonafterinfection.During thelaterstagesofinfection.basophilicinclusionsappearthat initiallymavbesurroundedbyaclearhalowithinthenucleus. Whentheseintranuclearinclusionsenlargeandobscurethe nuclearmembrane.thecellsaretermed'smudgecells'.Onelec— tronmicroscopy.icosahedralVl.rionsareseeninthenucleusand typicallyformlarge,paracrystallineaggregates.InsituDNAand immunohistochemicalassaysarealsoavailable. Serology:themostwidelyavailableassays(complement—fixation antibodiesandELISA)detectantibodiesthatreactagainstall adenovirusserotypes.Becauseofthehighprevalanceofantibodies Vol6No4Apr,2006Sexuallytransmittedlnfections 2H[stopathologyoF[uimlnantadenoviru~type5hepatitisina bonemarrowIrans口【antrecipientMultipleceil5with『nI?nuc[eat inclusionsatdifferentstagesarescatteredIhroughou[the hepaticparenchyma_Irrows)Anareaofnecrosisispresenti IhelowerpartofIhesenl0n M0sTadenovira1diseds~srplili】ti?1.ndtrcatII~E[1sGU IILIFt1VP}I,tetnaIsuperin『ecti…illny~)cl:llr.【herets…ta1Jl1?I If__fILlimmbeIit…l?v,3sIvuidRec~nliPpOlsu皓1 …『cldL~fovir.dbroadSl!eCm,mTT1pl'1spl1^,lucleolhlea,lfi vira1drc,~hasrnlldes~clhlicalac[Ivi【vd…s【.1?e…1口ldisease bliifLInl1r?ud【…r,leed~l AnntericcDa【_【…aI{iwiIhadenE)vTr【isn?i1[vp4 andgroupBtype7s]~ppiisuccessful}11l~revpiiII~pid,:mics [13cttrespiralo~ydisd#P【i1miIitP,ry【rdll_l?Rc,3illps Rplic;ltioi}eliclp[iladencwi~usisbeingin『1…Ieddv? d【VPC~~3TIorTmmLiniz~[iO1)agai1stDrhPri~ctiouspall^tis if1"iTlgHlmalari1(IEbola…rtl 【c【FLRiC.5 1LionBaumgartinserR.Wat~ingerFMolecula~monitoring ofadenovirusInperipheralbloodafterallogeneicbonemarrow tnsptantatioHpermcb口r]ydiagnosiso『d]ssemmaladd[sease ood2003;102:1120 2LegrandBerrebiD.HouhouNetelEarlydiagnosisofadenoviru~ infectlonandreatme~twithlldofovirafterbO…arrow transplanlat[oninchlIdrenBoneM…5口nf200127: 621—6 …}一HEI[^0' EdwardsKMtThompson』一oIJJet~Y,埘enDyjJ[r,.H5young ildrenPsdlotrlcs1985.,6:420—4 Ho~it7M5Adenovir~esin:FieldsBN.KnlpeDMHowieyPMeds 啦virology3rdeddDhiaLlpp]ncoltRaven1996: 2160—72 HowardDSPhillipsIIG.ReeceDEeta/Adenovirusinf…tT{ hematopoietlcstemcelltranDian『r~cTpienlsnIntectDI999 29:194501 (OescribestheincidenceandDu【c0meofade~ovirusinfectionsln 舯ediatrl[aadultients.aanaLysesriskfacIots[ordIse5e1 lernt~nJALowryB5.HaydenFGetfAdenovlrustype8…idmlr keratoconiunc[ivFIi…eye(1in|[:risk[a~torsandc口nIro1m D1993;167:1307—13 (Hishghstheprobtemsofdecontamlnat[0nofequipmentand Prevention0fpersorltopr50…rasmission1 ? 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MEDICINE,2005,33(5):128,130 腺病毒是引起婴幼儿发热常见的DNA病毒,通 常引起呼吸道感染,也可以有消化系统,眼部,神经 系统,泌尿生殖系统的现.通常腺病毒感染的病程 自限,但对于免疫抑制患者或一些健康儿童和成年人 偶可引起致死性侵袭性疾病. 流行病学 腺病毒感染分布全球,全年均可发生,有超过5O 个血清型,分为6组(AF).C组中的1,2和5血 清型常引起呼吸道感染,也是最常从人群中分离到的 型.传播途径为气溶胶,粪口途径或接触污染物.腺 病毒无包膜,在物体表面可以存活很长时间.脂类消 毒剂无效,对热,甲醛,氯敏感. 婴幼儿的发热性疾病中有5%,10%由腺病毒引起, 多数人群有在1O岁前感染腺病毒的血清学证据,普通 家庭及日托幼儿园中心都普遍存在该病毒,已经证实 腺病毒可在院内传播.腺病毒可以造成持续感染,粪 便持续排出病毒非常常见,对于免疫抑制患者,腺病 毒感染后的病毒再次激活是迁延性感染的可能原因. 腺病毒感染的流行病学实例如下: ?新兵中暴发的急性呼吸道感染 ?夏令营中使用公共游泳池和湖泊而出现的咽 结膜热 ?医疗机构中出现的出血性角结膜炎. 临床特点 腺病毒感染临床特点因年龄及免疫功能失调而各 ?Phyllisn0menberg是美国费城托马斯.杰弗逊大学传染病学顾 问医师.利益冲突:未声明. MEDICINEINTERNATICINAL 异(表1). 呼吸道腺病毒通常从引起幼儿发热的呼吸道 疾病中分离到.通常病程为5,7天,但症状可持续 14天. 表1腺病毒引起的疾病 婴儿 ?咽炎,鼻炎,肺炎 ?中耳炎 ?腹泻 儿童 ?上呼吸道疾病,肺炎 ?咽结膜热 ?腹泻.肠系膜淋巴结炎 ?出血性膀胱炎 年轻人 ?急性呼吸道疾病 成人 ?流行性角膜结膜炎 免疫抑制患者 ?肺炎 ?肠胃炎,肝炎 ?出血性膀胱炎,肾炎 ?脑膜脑炎 ?最初的诊断是咽炎,鼻炎和中耳炎. ?通常可发现渗出性扁桃体炎伴渗出物和颈部 淋巴结肿大,临床上与A族链球菌引起的扁桃体炎难 以鉴别. ?发热和其他全身表现(如全身不适,头痛, 肌痛,腹痛)常见. ?咽炎通常伴结膜炎,喉气管炎,支气管炎或 肺炎.少数情况下腺病毒可引起百日咳样综合征,不 伴皮疹和发热的细支气管炎,鼻炎. 腺病毒肺炎腺病毒(B组3,7和2l型最常 见)在儿童中引起的肺炎约占10%.婴儿肺炎比年长 儿肺炎严重,通常伴有嗜睡,腹泻,咽炎和结膜炎. 影像学显示与其他病毒性肺炎相似的双肺弥漫性渗出 性表现.病理改变为坏死性支气管炎,细支气管炎和 表现为单核细胞浸润,透明膜和坏死的肺炎.肺外并 发症包括脑膜脑炎,肝炎,心肌炎,肾炎,白细胞减 少,播散性血管内凝血.儿童感染的后遗症特别是支 气管扩张的发生率很高. 眼睛B组3和7型可以引起良性滤泡性结膜 ?2OO6"/beMedicinePublishingCompanyLtd 感染病学国际内科双语杂志2o06.Vo1.6.No.4 炎,可以单独发生也可伴发咽炎(咽结膜热).D组 8,19和37型主要引起严重的流行性角膜结膜炎,表 现为双侧结膜炎和耳前淋巴结肿大,随后发生角膜混 浊和角膜疼痛,可以引起视力持续损害. 消化道在幼儿中,5%,15%的急性腹泻由腺病 毒F组4O,4l型引起.其他腺病毒血清型偶引起肠 系膜淋巴结炎,类似于阑尾炎并偶引发肠套叠.肝炎 通常为婴儿腺病毒性肺炎的并发症.在免疫抑制的患 者,腺病毒感染可引起胃肠炎以及肝炎,主要病毒株 为C组5型. 泌尿生殖道腺病毒B组11,21型在男孩中通 常为出血性膀胱炎的不典型表现.偶有报道腺病毒19 型可以引起成人眼生殖道综合征.在免疫抑制的患 者,B组11,34,35型引起出血性膀胱炎,可以伴 或不伴肾炎. 神经系统偶尔报道腺病毒感染可以引起脑炎及 脑膜炎.神经系统累及可以是原发感染或伴发7型引 起的重症肺炎. 实验室研究 病毒培养是一种腺病毒的敏感.大部 分血清型在人上皮细胞和成纤维细胞中经过几天到几 周的培养后可以形成特征性细胞病变.在更快速的贝 壳瓶培养检测中,标本可以直接离心至细胞单层,孵 育1,2天,采用免疫荧光法可以检测到腺病毒蛋白. 腺病毒可以从咽部,鼻咽部,结膜,痰,尿,粪便, 脑脊液,血液或组织标本中培养提取.但是肠腺病毒 F组40,41型在常规细胞培养基中不能生长,粪便培 养的其他血清型的阳性提示可能为无症状性粪便排毒. 腺病毒抗原检测对临床标本进行酶联免疫吸附 法(ELISA)或免疫荧光法检测病毒抗原的敏感性低 于病毒培养法,但较快速.ELISA专用于对病毒培养 要求很高的4o,41血清型. 腺病毒DNA检测采用聚合酶链反应检测比病 毒培养更加敏感快速.对血标本进行PCR定量 可早期检测造血干细胞受者的腺病毒病.但是这些方 法需要更进一步的临床确认. 组织病理学腺病毒病可以通过组织病理切片中 细胞内特异性包涵体证实.细胞感染腺病毒后不久产 生小的嗜酸性包涵体,感染后期嗜碱性包涵体