herpesviruses(水痘带状疱疹病毒)课件

HerpesvirusesAnOverviewHerpesvirusesAnOverview1PropertiesofherpesvirusesEnvelopeddoublestrandedDNAviruses.Genomeconsisitsoflongandshortfragmentswhichmaybeorientatedineitherdirection,givingatotalof4isomers.Threesubfamilies:Alphaherpesviruses-HSV-1,HSV-2,VZVBetaherpesviruses-CMV,HHV-6,HHV-7Gammaherpesviruses-EBV,HHV-8SetuplatentorpersistentinfectionfollowingprimaryinfectionReactivationaremorelikelytotakeplaceduringperiodsofimmunosuppressionBothprimaryinfectionandreactivationarelikelytobemoreseriousinimmunocompromisedpatients.PropertiesofherpesvirusesEnv2HerpesvirusParticleHSV-2virusparticle.Notethatallherpesviruseshaveidenticalmorphologyandcannotbedistinguishedfromeachotherunderelectronmicroscopy.(LindaStannard,UniversityofCapeTown,S.A.)HerpesvirusParticleHSV-2viru3HerpesSimplexVirusesHerpesSimplexViruses4PropertiesBelongtothealphaherpesvirussubfamilyofherpesvirusesDoublestrandedDNAenvelopedviruswithagenomeofaround150kbThegenomeofHSV-1andHSV-2share50-70%homology.Theyalsoshareseveralcross-reactiveepitopeswitheachother.Thereisalsoantigeniccross-reactionwithVZV.ManistheonlynaturalhostforHSV.PropertiesBelongtothealphah5Epidemiology(1)HSVisspreadbycontact,asthevirusisshedinsaliva,tears,genitalandothersecretions.Byfarthemostcommonformofinfectionresultsfromakissgiventoachildoradultfromapersonsheddingthevirus.Primaryinfectionisusuallytrivialorsubclinicalinmostindividuals.Itisadiseasemainlyofveryyoungchildrenie.thosebelow5years.Thereare2peaksofincidence,thefirstat0-5yearsandthesecondinthelateteens,whensexualactivitycommences.About10%ofthepopulationacquiresHSVinfectionthroughthegenitalrouteandtheriskisconcentratedinyoungadulthood.Epidemiology(1)HSVisspread6Epidemiology(2)GenerallyHSV-1causesinfectionabovethebeltandHSV-2belowthebelt.Infact,40%ofclinicalisolatesfromgenitalsoresareHSV-1,and5%ofstrainsisolatedfromthefacialareaareHSV-2.Thisdataiscomplicatedbyoralsexualpractices.Followingprimaryinfection,45%oforallyinfectedindividualsand60%ofpatientswithgenitalherpeswillexperiencerecurrences.Theactualfrequencyofrecurrencesvarieswidelybetweenindividuals.Themeannumberofepisodesperyearisabout1.6.

Epidemiology(2)GenerallyHSV-7PathogenesisDuringtheprimaryinfection,HSVspreadslocallyandashort-livedviraemiaoccurs,wherebythevirusisdisseminatedinthebody.Spreadtothetocraniospinalgangliaoccurs.Thevirusthenestablisheslatencyinthecraniospinalganglia.Theexactmechanismoflatencyisnotknown,itmaybetruelatencywherethereisnoviralreplicationorviralpersistencewherethereisalowlevelofviralreplication.Reactivation

-Itiswellknownthatmanytriggerscanprovokearecurrence.Theseincludephysicalorpsychologicalstress,infection;especiallypneumococcalandmeningococcal,fever,irradiation;includingsunlight,andmenstruation.PathogenesisDuringtheprimary8ClinicalManifestations

HSVisinvolvedinavarietyofclinicalmanifestationswhichincludes;-1.Acutegingivostomatitis2.HerpesLabialis(coldsore)3.OcularHerpes4.HerpesGenitalis5.Otherformsofcutaneousherpes7.Meningitis8.Encephalitis9.NeonatalherpesClinicalManifestations HSVis9Oral-facialHerpesAcuteGingivostomatitisAcutegingivostomatitisisthecommonestmanifestationofprimaryherpeticinfection.Thepatientexperiencespainandbleedingofthegums.1-8mmulcerswithnecroticbasesarepresent.Neckglandsarecommonlyenlargedaccompaniedbyfever.Usuallyaselflimitingdiseasewhichlastsaround13days.Herpeslabialis(coldsore)

Followingprimaryinfection,45%oforallyinfectedindividualswillexperiencereactivation.Theactualfrequencyofrecurrencesvarieswidelybetweenindividuals.Herpeslabialis(coldsore)isarecurrenceoforalHSV.Aprodromeoftingling,warmthoritchingatthesiteusuallyheraldstherecurrence.About12hourslater,red­nessappearsfollowedbypapulesandthenvesicles.

Oral-facialHerpesAcuteGingiv10GingivostomatitisGingivostomatitis11OcularHerpes

HSVcausesabroadspectrumofoculardisease,rangingfrommildsuperficiallesionsinvolvingtheexternaleye,toseveresight-threateningdiseasesoftheinnereye.Diseasescausedincludethefollowing:-PrimaryHSVkeratitis–dendriticulcersRecurrentHSVkeratitisHSVconjunctivitisIridocyclitis,chorioretinitisandcataract

OcularHerpes HSVcausesabro12GenitalHerpesGenitallesionsmaybeprimary,recurrentorinitial.Manysitescanbeinvolvedwhichincludesthepenis,vagina,cervix,anus,vulva,bladder,thesacralnerveroutes,thespinalandthemeninges.Thelesionsofgenitalherpesareparticularlypronetosecondarybacterialinfectioneg.S.aureus,Streptococcus,TrichomonasandCandidaAlbicans.Dysuriaisacommoncomplaint,inseverecases,theremaybeurinaryretention.Localsensorynervesmaybeinvolvedleadingtothedevelopmentofaradiculitis.Amildmeningitismaybepresent.60%ofpatientswithgenitalherpeswillexperiencerecurrences.RecurrentlesionsintheperianalareatendtobemorenumerousandpersistslongerthantheiroralHSV-1counterparts.GenitalHerpesGenitallesions13HerpesSimplexEncephalitisHerpesSimplexencephalitisisoneofthemostseriouscomplicationsofherpessimplexdisease.Therearetwoforms:Neonatal–thereisglobalinvolvementandthebrainisalmostliquefied.Themortalityrateapproaches100%.Focaldisease–thetemporallobeismostcommonlyaffected.Thisformofthediseaseappearsinchildrenandadults.Itispossiblethatmanyofthesecasesarisefromreactivationofvirus.Themortalityrateishigh(70%)withouttreatment.ItisofutmostimportancetomakeadiagnosisofHSEearly.ItisgeneralpracticethatIVacyclovirisgiveninallcasesofsuspectedHSEbeforelaboratoryresultsareavailable.HerpesSimplexEncephalitisHer14NeonatalHerpesSimplex(1)IncidenceofneonatalHSVinfectionvariesinexplicablyfromcountrytocountrye.g.from1in4000livebirthsintheU.S.to1in10000livebirthsintheUKThebabyisusuallyinfectedperinatallyduringpassagethroughthebirthcanal.Prematurerupturingofthemembranesisawellrecognizedriskfactor.Theriskofperinataltransmissionisgreatestwhenthereisafloridprimaryinfectioninthemother.Thereisanappreciablysmallerriskfromrecurrentlesionsinthemother,probablybecauseofthelowerviralloadandthepresenceofspecificantibodyThebabymayalsobeinfectedfromothersourcessuchasorallesionsfromthemotheroraherpeticwhitlowinanurse.NeonatalHerpesSimplex(1)Inc15NeonatalHerpesSimplex(2)ThespectrumofneonatalHSVinfectionvariesfromamilddiseaselocalizedtotheskintoafataldisseminatedinfection.Infectionisparticularlydangerousinprematureinfants.Wheredisseminationoccurs,theorgansmostcommonlyinvolvedaretheliver,adrenalsandthebrain.Wherethebrainisinvolved,theprognosisisparticularlysevere.Theencephalitisisglobalandofsuchseveritythatthebrainmaybeliquefied.AlargeproportionofsurvivorsofneonatalHSVinfectionhaveresidualdisabilities.AcyclovirshouldbepromptlygiveninallsuspectedcasesofneonatalHSVinfection.TheonlymeansofpreventionistooffercaesareansectiontomotherswithfloridgenitalHSVlesions.

NeonatalHerpesSimplex(2)The16OtherManifestationsDisseminatedherpessimplexaremuchmorelikelytooccurinimmunocompromisedindividuals.Thewidespreadvesicularresemblesthatofchickenpox.Manyorgansotherthantheskinmaybeinvolvede.g.liver,spleen,lungs,andCNS.Othercutaneousmanifestationsincludeeczemaherpeticumwhichispotentiallyaseriousdiseasethatoccursinpatientswitheczema.Herpeticwhitlowwhicharisefromimplantationofthevirusintotheskinandtypicallyaffectthefingers.“zosteriformherpessimplex".ThisisararepresentationofherpessimplexwhereHSVlesionsappearinadermatomaldistributionsimilartoherpeszoster.

OtherManifestationsDisseminat17LaboratoryDiagnosisDirectDetectionElectronmicroscopyofvesiclefluid-rapidresultbutcannotdistinguishbetweenHSVandVZVImmunofluorescenceofskinscrappings-candistinguishbetweenHSVandVZVPCR-nowusedroutinelyforthediagnosisofherpessimpleencephalitisVirusIsolation

HSV-1andHSV-2areamongtheeasiestvirusestocultivate.Itusuallytakesonly1-5daysforaresulttobeavailable.SerologyNotthatusefulintheacutephasebecauseittakes1-2weeksforbeforeantibodiesappearafterinfection.Usedtodocumenttorecentinfection.LaboratoryDiagnosisDirectDet18CytopathicEffectofHSVincellculture:Notetheballooningofcells.(LindaStannard,UniversityofCapeTown,S.A.)

PositiveimmunofluorescencetestforHSVantigeninepithelialcell.(VirologyLaboratory,New-YaleHavenHospital)CytopathicEffectofHSVince19ManagementAtpresent,thereareonlyafewindicationsofantiviralchemo­therapy,withthehighcostofantiviraldrugsbeingamainconsideration.Generally,antiviralchemotherapyisindicatedwheretheprimaryinfectionisespeciallysevere,wherethereisdissemination,wheresightisthreatened,andherpessimplexencephalitis.Acyclovir–thisthedrugofchoiceformostsituationsatpresent.Itisavailableinanumberofformulations:-I.V.(HSVinfectioninnormalandimmunocompromisedpatients)Oral(treatmentandlongtermsuppressionofmucocutaneousherpesandprophylaxisofHSVinimmunocompromisedpatients)Cream(HSVinfectionoftheskinandmucousmembranes)OphthalmicointmentFamciclovirandvalacyclovir–oralonly,moreexpensivethanacyclovir.Otherolderagents–e.g.idoxuridine,trifluorothymidine,Vidarabine(ara-A).Theseagentsarehighlytoxicandissuitablefortopicaluseforopthalmicinfectiononly

ManagementAtpresent,therear20Varicella-ZosterVirusVaricella-ZosterVirus21PropertiesBelongtothealphaherpesvirussubfamilyofherpesvirusesDoublestrandedDNAenvelopedvirusGenomesize125kbp,longandshortfragmentswithatotalof4isometricforms.Oneantigenicserotypeonly,althoughthereissomecrossreactionwithHSV.PropertiesBelongtothealphah22EpidemiologyPrimaryvaricellaisanendemicdisease.Varicellaisoneoftheclassicdiseasesofchildhood,withthehighestprevalenceoccurringinthe4-10yearsoldagegroup.Varicellaishighlycommunicable,withanattackrateof90%inclosecontacts.Mostpeoplebecomeinfectedbeforeadulthoodbut10%ofyoungadultsremainsusceptible.Herpeszoster,incontrast,occurssporadicallyandevenlythroughouttheyear.EpidemiologyPrimaryvaricella23PathogenesisThevirusisthoughttogainentryviatherespiratorytractandspreadsshortlyaftertothelymphoidsystem.Afteranincubationperiodof14days,thevirusarrivesatitsmaintargetorgan,theskin.Followingtheprimaryinfection,thevirusremainslatentinthecerebralorposteriorrootganglia.In10-20%ofindividuals,asinglerecurrentinfectionoccursafterseveraldecades.Thevirusreactivatesintheganglionandtracksdownthesensorynervetotheareaoftheskininnervatedbythenerve,producingavaricellaformrashinthedistributionofadermatome.

PathogenesisThevirusisthoug24VaricellaPrimaryinfectionresultsinvaricella(chickenpox)Incubationperiodof14-21daysPresentsfever,lymphadadenopathy.awidespreadvesicularrash.Thefeaturesaresocharacteristicthatadiagnosiscanusuallybemadeonclinicalgroundsalone.Complicationsarerarebutoccursmorefrequentlyandwithgreaterseverityinadultsandimmunocompromisedpatients.Mostcommoncomplicationissecondarybacterialinfectionofthevesicles.Severecomplicationswhichmaybelifethreateningincludeviralpneumonia,encephalititis,andhaemorrhagicchickenpox.VaricellaPrimaryinfectionres25RashofChickenpoxRashofChickenpox26HerpesZoster(Shingles)HerpesZostermainlyaffectasingledermatomeoftheskin.Itmayoccuratanyagebutthevastmajorityofpatientsaremorethan50yearsofage.Thelatentvirusreactivatesinasensoryganglionandtracksdownthesensorynervetotheappropriatesegment.Thereisacharacteristiceruptionofvesiclesinthedermatomewhichisoftenaccompaniedbyintensivepainwhichmaylastformonths(postherpeticneuralgia)Herpeszosteraffectingtheeyeandfacemayposegreatproblems.Aswithvaricella,herpeszosterinafargreaterprobleminimmunocompromisedpatientsinwhomthereactivationoccursearlierinlifeandmultipleattacksoccuraswellascomplications.Complicationsarerareandincludeencephalitisanddisseminatedherpeszoster.HerpesZoster(Shingles)Herpes27ShinglesShingles28CongenitalVZVInfection90%ofpregnantwomenalreadyimmune,thereforeprimaryinfectionisrareduringpregnancy.Primaryinfectionduringpregnancycarriesagreaterriskofseveredisease,inparticularpneumonia.First20weeksofPregnancyUpto3%chanceoftransmissiontothefetus,recognisedcongenitalvaricellasyndrome;ScarringofskinHypoplasiaoflimbsCNSandeyedefectsDeathininfancynormalCongenitalVZVInfection90%of29NeonatalVaricellaVZVcancrosstheplacentainthelatestagesofpregnancytoinfectthefetuscongenitally.Neonatalvaricellamayvaryfromamilddiseasetoafataldisseminatedinfection.Ifrashinmotheroccursmorethan1weekbeforedelivery,thensufficientimmunitywouldhavebeentransferredtothefetus.Zosterimmunoglobulinshouldbegiventosusceptiblepregnantwomenwhohadcontactwithsuspectedcasesofvaricella.Zosterimmunoglobulinshouldalsobegiventoinfantswhosemothersdevelopvaricelladuringthelast7daysofpregnancyorthefirst14daysafterdelivery.NeonatalVaricellaVZVcancros30LaboratoryDiagnosisTheclinicalpresentationsofvaricellaorzosteraresocharacteristicthatlaboratoryconfirmationisrarelyrequired.Laboratorydiagnosisisrequiredonlyforatypicalpresentations,particularlyintheimmunocompromised.VirusIsolation-rarelycarriedoutasitrequires2-3weeksforaresults.Directdetection-electronmicroscopymaybeusedforvesiclefluidsbutcannotdistinguishbetweenHSVandVZV.Immunofluorescenseonskinscrappingscandistinguishbetweenthetwo.Serology-thepresenceofVZVIgGisindicativeofpastinfectionandimmunity.ThepresenceofIgMisindicativeofrecentprimaryinfection.LaboratoryDiagnosisTheclinic31CytopathicEffectofVZVincellculture:Notetheballooningofcells.(CoutesyofLindaStannard,UniversityofCapeTown,S.A.)CytopathicEffectofVZVCytopathicEffectofVZVince32ManagementUncomplicatedvaricellaisaselflimiteddiseaseandrequiresnospecifictreatment.However,acyclovirhadbeenshowntoacceleratetheresolutionofthediseaseandisprescribedbysomedoctors.Acyclovirshouldbegivenpromptlyimmunocompromisedindividualswithvaricellainfectionandnormalindividualswithseriouscomplicationssuchaspneumoniaandencephalitis.herpeszosterinahealthyindividualisnotnormallyacauseforconcern.Themainproblemisthemanagementofthepostherpeticneuralgia.TheInternationalHerpesManagementForumrecommendsthatantiviraltherapyshouldbeofferedroutinelytoallpatientsover50yearsofagepresentingwithherpeszoster.Threedrugscanbeusedforthetreatmentofherpeszoster:acyclovir,valicyclovir,andfamciclovir.Thereappearstobelittledifferenceinefficacybetweenthem.ManagementUncomplicatedvarice33PreventionPreventivemeasuresshouldbeconsideredforindividualsatriskofcontractingseverevaricellainfectione.g.leukaemicchildren,neonates,andpregnantwomenWhereurgentprotectionisneeded,passiveimmunizationshouldbegiven.Zosterimmunoglobulin(ZIG)isthepreparationofchoicebutitisveryexpensive.WhereZIGisnotavailable,HNIGshouldbegiveninstead.Aliveattenuatedvaccineisavailable.Therehadbeengreatreluctancetouseitinthepast,especiallyinimmunocompromisedindividualssincethevaccineviruscanbecomelatentandreactivatelateron.However,recentdatasuggeststhatthevaccineissafe,eveninchildrenwithleukaemiaprovidedthattheyareinremission.Itishighlydebatablewhetheruniversalvaccinationshouldbeofferedsincechickenpoxandshinglesarenormallymilddiseases.PreventionPreventivemeasures34CytomegalovirusCytomegalovirus35PropertiesBelongtothebetaherpesvirussubfamilyofherpesvirusesdoublestrandedDNAenvelopedvirusNucleocapsid105nmindiameter,162capsomersThestructureofthegenomeofCMVissimilartootherherpesviruses,consistingoflongandshortsegmentswhichmaybeorientatedineitherdirection,givingatotalof4isomers.Alargeno.ofproteinsareencodedfor,theprecisenumberisunknown.PropertiesBelongtothebetahe36EpidemiologyCMVisoneofthemostsuccessfulhumanpathogens,itcanbetransmittedverticallyorhorizontallyusuallywithlittleeffectonthehost.Transmissionmayoccurinutero,perinatallyorpostnatally.Onceinfected,thepersoncarriesthevirusforlifewhichmaybeactivatedfromtimetotime,duringwhichinfectiousvirionsappearintheurineandthesaliva.Reactivationcanalsoleadtoverticaltransmission.ItisalsopossibleforpeoplewhohaveexperiencedprimaryinfectiontobereinfectedwithanotherorthesamestrainofCMV,thisreinfectiondoesnotdifferclinicallyfromreactivation.Indevelopedcountrieswithahighstandardofhygiene,40%ofadolescentsareinfectedandultimately70%ofthepopulationisinfected.Indevelopingcountries,over90%ofpeopleareultimatelyinfected.EpidemiologyCMVisoneofthe37PathogenesisOnceinfected,thevirusremainsinthepersonforlifeandmybereactivatedfromtimetotime,especiallyinimmunocompromisedindividuals.Thevirusmaybetransmittedinutero,perinatally,orpostnatally.Perinataltransmissionoccurs.Perinatalinfectionisacquiredmainlythroughinfectedgenitalsecretions,orbreastmilk.Overall,2-10%ofinfantsareinfectedbytheageof6monthsworldwide.Perinatalinfectionisthoughttobe10timesmorecommonthancongenitalinfection.Postnatalinfectionmainlyoccursthroughsaliva.Sexualtransmissionmayoccuraswellasthroughbloodandbloodproductsandtransplantedorgan.PathogenesisOnceinfected,the38ClinicalManifestationsCongenitalinfection-mayresultincytomegalicinclusiondiseasePerinatalinfection-usuallyasymptomaticPostnatalinfection-usuallyasymptomatic.However,inaminorityofcases,thesyndromeofinfectiousmononucleosismaydevelopwhichconsistsoffever,lymphadenopathy,andsplenomegaly.Theheterophilantibodytestisnegativealthoughatypicallymphocytesmaybefoundintheblood.ImmunocompromisedpatientssuchastransplantrecipientsandAIDSpatientsarepronetosevereCMVdiseasesuchaspneumonitis,retinitis,colitis,andencephalopathy.ReactivationorreinfectionwithCMVisusuallyasymptomaticexceptinimmunocompromisedpatients.ClinicalManifestationsCongeni39CongenitalInfectionDefinedastheisolationofCMVfromthesalivaorurinewithin3weeksofbirth.Commonestcongenitalviralinfection,affects0.3-1%ofalllivebirths.ThesecondmostcommoncauseofmentalhandicapafterDown'ssyndromeandisresponsibleformorecasesofcongenitaldamagethanrubella.TransmissiontothefetusmayoccurfollowingprimaryorrecurrentCMVinfection.40%chanceoftransmissiontothefetusfollowingaprimaryinfection.Maybetransmittedtothefetusduringallstagesofpregnancy.Noevidenceofteratogenecity,damagetothefetusresultsfromdestructionoftargetcellsoncetheyareformed.CongenitalInfectionDefineda40CytomegalicInclusionDiseaseCNSabnormalities-microcephaly,mentalretardation,spasticity,epilepsy,periventricularcalcification.Eye-choroidoretinitisandopticatrophyEar-sensorineuraldeafnessLiver-hepatosplenomegalyandjaundicewhichisduetohepatitis.Lung-pneumonitisHeart-myocarditisThrombocytopenicpurpura,HaemolyticanaemiaLatesequelaeinindividualsasymptomaticatbirth-hearingdefectsandreducedintelligence.CytomegalicInclusionDiseaseC41IncidenceofCytomegalicDiseaseIncidenceofCytomegalicDisea42LaboratoryDiagnosis(1)Directdetection

biopsyspecimensmaybeexaminedhistologicallyforCMVinclusionantibodiesorforthepresenceofCMVantigens.However,thesensitivitymaybelow.Thepp65CMVantigenaemiatestisnowroutinelyusedfortherapiddiagnosisofCMVinfectioninimmunocompromisedpatients.PCRforCMV-DNAisusedinsomecentersbuttheremaybeproblemswithinterpretation.LaboratoryDiagnosis(1)Direct43CMVpp65antigenaemiatest(VirologyLaboratory,New-YaleHavenHospital)CMVpp65antigenaemiatest(Vir44LaboratoryDiagnosis(2)VirusIsolationconventionalcellcultureisregardedasgoldstandardbutrequiresupto4weeksforresult.MoreusefularerapidculturemethodssuchastheDEAFFtestwhichcanprovidearesultin24-48hours.Serology

thepresenceofCMVIgGantibodyindicatespastinfection.ThedetectionofIgMisindicativeofprimaryinfectionalthoughitmayalsobefoundinimmunocompromisedpatientswithreactivation.LaboratoryDiagnosis(2)Virus45CytopathicEffectofCMV(CourtesyofLindaStannard,UniversityofCapeTown,S.A.)CytopathicEffectofCMV(Court46DEAFFtestforCMV(VirologyLaboratory,New-YaleHavenHospital)DEAFFtestforCMV(VirologyLa47SpecimensforLaboratoryDiagnosisSpecimensforLaboratoryDiagn48TreatmentCongenitalinfections-itisnotusuallypossibletodetectcongenitalinfectionunlessthemotherhassymptomsofprimaryinfection.Ifso,thenthemothershouldbetoldofthechancesofherbabyhavingcytomegalicinclusiondiseaseandperhapsofferedthechoiceofanabortion.Perinatalandpostnatalinfection-itisusuallynotnecessarytotreatsuchpatients.Immunocompromisedpatients-itisnecessarytomakeadiagnosisofCMVinfectionearlyandgivepromptantiviraltherapy.Anti-CMVagentsincurrentuseareganciclovir,forscarnet,andcidofovir.TreatmentCongenitalinfections49PreventionNolicensedvaccineisavailable.ThereisacandidateliveattenuatedvaccineknownastheTownestrainbutthereareconcernsaboutadministeringalivevaccinewhichcouldbecomelatentandreactivates.PreventionofCMVdiseaseintransplantrecipientsisaverycomplicatedsubjectandvariesfromcentertocenter.Itmayincludethefollowingmeasures.ScreeningandmatchingtheCMVstatusofthedonorandrecipientUseofCMVnegativebloodfortransfusionsAdministrationofCMVimmunoglobulintoseronegativerecipientspriortotransplantGiveantiviralagentssuchasacyclovirandganciclovirprophylactically.PreventionNolicensedvaccine50Epstein-BarrVirusEpstein-BarrVirus51Epstein-BarrVirus(EBV)BelongtothegammaherpesvirussubfamilyofherpesvirusesNucleocapsid100nmindiameter,with162capsomersMembraneisderivedbybuddingofimmatureparticlesthroughcellmembraneandisrequiredforinfectivity.GenomeisalineardoublestrandedDNAmoleculewith172kbpTheviralgenomedoesnotnormallyintegrateintothecellularDNAbutformscircularepisomeswhichresideinthenucleus.Thegenomeislargeenoughtocodefor100-200proteinsbutonlyafewhavebeenidentified.Epstein-BarrVirus(EBV)Belong52EpidemiologyTwoepidemiologicalpatternsareseenwithEBV.Indevelopedcountries,2peaksofinfectionareseen:thefirstinveryyoungpreschoolchildrenaged1-6andthesecondinadolescentsandyoungadultsaged14-20Eventually80-90%ofadultsareinfected.Indevelopingcountries,infectionoccursatamuchearlieragesothatbytheageoftwo,90%ofchildrenareseropositive.Thevirusistransmittedbycontactwithsaliva,inparticularlythroughkissing.EpidemiologyTwoepidemiologica53PathogenesisOnceinfected,alifelongcarrierstatedevelopswherebyalowgradeinfectioniskeptincheckbytheimmunedefenses.Lowgradevirusreplicationandsheddingcanbedemonstratedintheepithelialcellsofthepharynxofallseropositiveindividuals.EBVisabletoimmortalizeB-lymphocytesinvitroandinvivoFurthermoreafewEBV-immortalizedB-cellscanbedemonstratedinthecirculationwhicharecontinuallyclearedbyimmunesurveillancemechanisms.EBVisassociatedwithseveralverydifferentdiseaseswhereitmayactdirectlyoroneofseveralco-factors.PathogenesisOnceinfected,al54DiseaseAssociation1.InfectiousMononucleosis2.Burkitt'slymphoma3.Nasopharyngealcarcinoma4.Lymphoproliferativediseaseandlymphomaintheimmunosuppressed.5.X-linkedlymphoproliferativesyndrome6.Chronicinfectiousmononucleosis7.OralleukoplakiainAIDSpatients8.ChronicinterstitialpneumonitisinAIDSpatients.

DiseaseAssociation1.Infectio55InfectiousMononuclosisPrimaryEBVinfectionisusuallysubclinicalinchildhood.Howeverinadolescentsandadults,thereisa50%chancethatthesyndromeofinfectiousmononucleosis(IM)willdevelop.IMisusuallyaself-limiteddiseasewhichconsistsoffever,lymphadenopathyandsplenomegaly.Insomepatientsjaundicemaybeseenwhichisduetohepatitis.Atypicallymphocytesarepresentintheblood.Complicationsoccurrarelybutmaybeseriouse.g.splenicrupture,meningoencephalitis,andpharyngealobstruction.Insomepatients,chronicIMmayoccurwhereeventuallythepatientdiesoflymphoproliferativediseaseorlymphoma.DiagnosisofIMisusuallymadebytheheterophilantibodytestand/ordetectionofEBVIgM.Thereisnospecifictreatment.InfectiousMononuclosisPrimary56Burkitt’sLymphoma(1)Burkitt'slymphoma(BL)occursendemicallyinpartsofAfrica(whereitisthecommonestchildhoodtumour)andPapuaNewGuinea.Itusuallyoccursinchildrenaged3-14years.Itrespondfavorablytochemotherapy.Itisrestrictedtoareaswithholoendemicmalaria.Thereforeitappearsthatmalariainfectionisacofactor.MultiplecopiesofEBVgenomeand