伪狂犬病的控制和清除.ppt

PSEUDORABIESControlandEradication伪狂犬病的控制和清除,朱稳森美国谷物协会广州,Pseudorabies伪狂犬病PRV伪狂犬病病毒AujeskysDisease(AD)奥叶斯基病InfectiousBulbarParalysis感染性延髓麻痹HistoricalRecordsreportdiseaseinCattleinearly1800s早在1800年有报道该病发生于牛Allspeciesofmammalssusceptible.哺乳动物易感Cats,Dogs,Sheep,Cattle,Horses,Rats,Monkeys.Manisresistant.RarereportsinHumans(Skinrash).人有抵抗性，人感染的报道很少见（皮疹）PRVwasoftenconfusedwithswinefever.常与猪瘟相混,急性：流产，木乃伊，死胎，不孕腹泻，中枢神经症状Highmortalityinsmallpigs仔猪高死亡率Pre-weancanbealmost100%断奶前几乎1005-9weekslessthan10%59周龄低于10Lessthan2%inolderpigs稍大猪低于2Coughing,sneezing咳嗽，喷嚏Skinlesions/Itching(notcommon)皮肤病变/痒（不多见）Varyingpathogenicity,sometimesacuteformnotseen病毒的致病性不同，有时未见急性型,慢性：PneumoniainGrow-finish生长肥育阶段肺炎Immunityfromsowlastsforupto15weeks,protective6to12weeks母体免疫力可持续到15周龄，但保护性只到612周龄Immunosuppression,SecondaryInfection免疫抑制，继发感染APP,Strep,MycoplasmaInteractionsSowherdfairlystable,G/Fisvirusfactory母猪群很稳定，生长肥育猪产生病毒Immunitycanbecyclicinsowherd母猪群免疫力可循环,PseudorabiesSpread伪狂犬病的传播InfectedPigs-病猪LifetimeLatentinfection潜伏感染VirusSheddingwhenstressed应激状态下产生病毒Fomites污染物Trucks,Boots,Premises卡车，靴子，环境Aerosol空气传播Spreads3kmveryeasily很容易就能传播3公里Circle/AreaVaccinationEssential环形/区域免疫是必需的,PRV-RouteofInfection感染途径Intranasal/oralroute鼻腔/口腔途径NasalEpithelialcells鼻腔上皮细胞NerveCells-upnervestoCNS神经细胞向上至中枢神经系统Tonsil扁桃体RespiratoryTract呼吸道LymphoidTissues淋巴组织Semen/Uterineroutepossible可能的精液/子宫途径,AfterInfection:感染后ThePigshedsvirusfor10to14days.1014天期间产生病毒VirusbecomesLatentinNerveTissue.病毒在神经组织潜伏PigisinfectedforitsLifetime.终生感染Periodicrecrudescenceoccurs.周期性复发LatentInfectionisdetectablebyPCR.PCR技术可检测潜伏感染,GrossLesions总体病变SometimesNoGrossLesionsarevisible有时见不到总体病变MultipleWhiteFocionLiver&Spleen肝脏和脾脏多个白色病灶Intranasal/tonsillarNecrosis(notcommon)鼻腔/扁桃体坏死（不常见）PulmonaryEdema肺水肿Pneumonia肺炎FacialSkinLesionsarerare.面部皮肤病变少见,MicroscopicLesions镜检病变Meningitis脑膜炎Encephalitis（大）脑炎PerivascularCuffing血管周成套现象Bronchitis支气管炎InterstitialPneumonia间质性肺炎NecroticFociinLiver&Spleen肝脏和脾脏的坏死性病灶EntericLesions肠道病变,DifferentialDiagnosis鉴别诊断SwineInfluenza猪流感Parvovirus细小病毒Circoviral“ShakerPigDisease”环状病毒性猪震颤病ClassicalSwineFever经典型猪瘟PRRS蓝耳病Enterovirus肠病毒,ConfirmedDiagnosis明确诊断VirusIsolation病毒分离FluorescentAntibodyTissueSection荧光抗体组织切片Serology血清学SerumNeutralization(SN)-Reliable,givesserumtiter血清中和反应（SN）可靠，给出滴度ELISA-Sensitive,specific,DifferentialELISA灵敏，特异性强，区别明显LatexAgglutination(LAT)-Verysensitive,cangivefalsepositive(dilute1:40mayhelp)胶乳凝集反应灵敏，可能假阳性（稀释40倍好些）PCR,In-SituHybridization,Etc.PCR，原位杂交，等,681012141618202224周,伪狂犬病免疫模型,x,x,x,x,x,0,1,0.3,0.4,感染母猪,感染仔猪,阳性,阴性,24681012141618202224,抗体水平,周龄,伪狂犬病gE(gI)ELISA,gE(gI),EconomicLossduetoPseudorabies伪狂犬病带来的经济损失,LossesduetoAcuteOutbreaks急性爆发的损失ReproductionProblems繁殖障碍PigletMortality仔猪死亡率ChronicForm慢性型Pneumonia肺炎Immunosuppression免疫抑制LossesinGrowing/Finishingupto$12USD/pig生长肥育阶段的损失可达12美元/头猪CostofVaccination疫苗成本LostAccesstoMarkets市场的损失,PercentLungDamage,支原体,支原体+伪狂犬病,InteractionofPRVandMycoplasmaInfection支原体与伪狂犬病的互作,0,1,0.3,0.4,感染母猪,感染仔猪,阳性,阴性,24681012141618202224,抗体水平,周龄,伪狂犬病gE(gI)ELISA,gE(gI),MajorGenesofPseudorabiesVirus伪狂犬病病毒的主要基因,gE(gI)Deletionrendersvirusavirulent.缺失后失去毒力ReliableELISA,PCRdifferentialtesting.ELISA，PCR可用于鉴别检测gG(gX)Commondeletioninvaccine.疫苗中通常缺失DifferentialELISAlessdistinctthanforgEELISA的鉴别检测结果不如对gE效果好,MajorGenesofPseudorabiesVirus,TK(thymidinekinase)胸腺嘧啶激酶Popularsafetydeletion常见安全缺失Deletioninhibitsvirusreplication缺失抑制病毒复制gI(gp63)Sometimesdeletedtoreducevirulence缺失可减弱毒力Notveryimportantinimmunization.在免疫作用中不重要,MajorGenesofPseudorabiesVirus,gB(gII)Usefulininductionofprotectiveimmunity益于产生保护性免疫力gC(gIII)Sometimesdeleted.DifferentialElisaAvailable有时缺失，可用ELISA鉴别gD(gp50)gDcontrolsabilityofvirustopenetratecells.gDimportantinImmunization.控制病毒对细胞的穿透能力，对免疫重要AntibodyagainstgB,gCorgDcanprotectpigs对gB,gC或gD抗体可保护猪,ImmunitytoPseudorabiesLocalImmunity局部免疫HumoralImmunity激素免疫CellularImmunity细胞免疫Interferon干扰素PreventionofLatency(occupysites)预防潜伏感染Antibodytitersarenomeasureofprotection(Kit,etal.1994,Boersmaetal.1998)抗体滴度不能衡量保护能力,PseudorabiesVaccination伪狂犬病的免疫VaccinationDoesNotProduceAbsoluteProtection免疫不能提供绝对的保护VaccinatedPigscanstillgettheInfection免疫后的猪仍可感染VaccinatedPigscanstillProduceVirus免疫后的猪可产生病毒VaccinatedPigscanstillGetSick免疫后的猪可发病VaccinationisUseful,andisCost-Effective免疫有用，且合算,PseudorabiesVaccinationCan:免疫能：ReduceLikelyhoodofInfection减少感染可能性ReduceSeverityandLengthofIllnessifpigisinfected万一猪感染，可缩短病程，减弱病情ReduceLengthofTimethatVirusisProduced(4x)缩短病毒产生时间ReduceAmountofVirusthatisProduced(1000 x)减少产生的病毒量ReduceLikelyhoodofLatentInfection减少潜伏感染机会ReduceLikelyhoodofRecrudescence减少反复感染机会,6810121416周,伪狂犬病免疫模型,MaternalAntibody母源抗体Pigletsverywellprotectedatleastuntilafterweaning.至少可为仔猪提供到断奶前的保护Generallyprotectionisweakbyweek8-12,andpigletmaybecomeinfected.812周龄前保护力减弱，猪可能感染SignificantPotentialInterferencewithImmunization.对疫苗有明显潜在干扰Latevaccination(10-16weeks)giveshighestAbresponse,butmaybetoolateforprotection.1016周龄免疫可产生高抗体反应，但来不及提供保护IntranasalvaccinationcircumventsmaternalAb.鼻腔免疫接种避开母源抗体,AllmaternalPRVAbdisappearsby16weeksofage.母源抗体到16周龄前消失PigsreceivingcolostrumfrominfectedsowswillbegE-Positiveforupto16weeksofage.吃到感染母猪初乳的仔猪16周龄前是gE阳性MaternalAntibodyhasahalf-lifeofabout10days.母源抗体的半衰期大约10天MaternalAbfordiseaseslikeStrep,Mycoplasma,APPonlylasts3-4weeks.ParvovirusmaternalAbmaylastaslongas6months.PRRSAblastsupto8weeksbutonlyprotectiveforabout3weeksorless.对链球菌，支原体，猪放线杆菌的母源抗体可持续34周，细小病毒母源抗体持续6个月，蓝耳病的母源抗体可持续8周，但只能保护到3周龄或更小。,6810121416周,伪狂犬病免疫模型,RouteofVaccination免疫途径Intranasal鼻腔RapidInductionofLocalImmunity很快产生局部免疫CanImmunizePigletsinpresenceofMaternalAb有母源抗体存在时可免疫仔猪CanBlockLatency阻断潜伏感染Intramuscular肌肉Convenient方便PracticalforLargeSwine对大猪可行UseLongNeedle需要长针头Intradermal-Experimentallyused皮内用于试验,未接种,肌肉注射,鼻腔免疫,IntranasalVaccinationReducesVirusSheddingafterSevereExperimentalChallenge试验性严重感染后鼻腔接种可减少病毒产生,PercentageofPigsSheddingVirus,ChoosingaPseudorabiesVaccine选择伪狂犬病疫苗,UseavaccinewithagE(g1)deletion.用gE缺失苗Youwillwanttobeabletodifferentiateinfectedanduninfectedpigs.可能想区别感染和未感染猪ModifiedLiveVirusshouldbeusedforinitialvaccinations.初次免疫应使用弱毒苗ModifiedLiveVirusorKilledviruscanbeusedforrepeatvaccinations.重复免疫时可用弱毒苗或灭活苗KilledvirusmayproducehigherAblevelsonrepeatvaccination.重复免疫时灭活苗可产生较高抗体水平,SelectingAppropriateTimeforVaccination正确选择免疫时机,Sows:母猪Conventionalthinkingistovaccinatebeforefarrowingtomakesurepigletsareprotected.一般认为产前免疫可保护仔猪Problem-Somesowsdonotfarrow,thusarenotvaccinated,andtheirimmunelevelcandeclinebelowtheprotectionlevel.问题一些母猪不分娩，未被免疫，其免疫水平低于能提供保护的水平Ifimmunelevelsfalltoolow,infectedsowswillbegintoshedvirus,anduninfectedsowswillbecomesusceptible.免疫水平过低，感染母猪产生病毒，未感染母猪易感,Vaccinatingsows3to4timeseachyearwillstabilizesowherdimmunityandpreventshedding.每年免疫母猪34次，可稳定群体免疫水平，防止产生病毒Preferableprogramistovaccinatesowherdenmasseat3to4monthintervalsbythecalendar.最好根据日历定期给母猪群体免疫，间隔34月Sowsshouldbevaccinatedregardlessofstageofreproduction,pregnancyorlactation.不考虑繁殖阶段，妊娠或泌乳，母猪全部免疫Whensowsarevaccinatedinthisway,theywillshedverylittlevirusandcanresistinfection.如此，母猪很少产生病毒，可抵抗感染Immunitylevelsareadequatetoprotectpiglets.其免疫力足可保护仔猪,ReplacementBoarsandGilts后备公母猪,Replacementanimalsshouldbevaccinatedtwiceat3weekintervalswithMLVvaccinebeforeentryintotheherd.后备猪在进群前应以弱毒苗免疫2次，间隔3周Ifnegativeboarsandgiltsentertheherdandtheherdisvaccinated3to4timesperyear,andinfectedanimalsaregraduallyculledwithrespectgiventotheirstatus,theherdwillbecomenegativein3to4years.阴性猪转入定期免疫的群体，感染猪逐渐被淘汰，群体可望在34年后转为阴性,Pigletvaccination仔猪免疫,Aserologicsurveyoftheherdwithanimalsatdifferentagestestedwillyieldvaluableinformation.对群体各年龄段作血清学调查可提供有价值信息Thetimeofinfectionanddecayofmaternalantibodywilldictatethetimeofvaccination.根据感染时间和母体免疫力的消退可决定免疫时间Thetraditionaltimesofvaccinationareto10and14weeksofage.传统免疫时间是10和14周龄Wheninfectionisoccurringatarelativelyyoungage,earliervaccinationmaybeindicated.一旦感染发生在早期，意味着应提早免疫,Presenceofmaternalantibodymayinterferewithearlyintramuscularvaccination.早期肌肉免疫可能受到母源抗体干扰Pigsmaybesuccessfullyvaccinatedintranasallyevenatbirthinthepresenceofmaternalantibody,buttheimmunitymayberelativelyshortlived.出生时的鼻腔接种可不受母源抗体干扰，但免疫力时间短Veryearly(atbirth)vaccinationshouldbefollowedwithaintranasalboosterat3-4weeksofage,andanintramuscularboosterat7to9weeksofage.出生免疫后应在34周龄时鼻腔接种和79周龄时肌肉免疫进行强化Whenvaccinatingat3-4weeksofage,asingleIMboosterat7to9weeksofageshouldbesufficient.首次免疫在34周龄时，79周龄时肌肉免疫强化一次足够,6810121416周,伪狂犬病免疫模型,0,1,0.3,0.4,感染母猪,感染仔猪,阳性,阴性,24681012141618202224,抗体水平,周龄,伪狂犬病gE(gI)ELISA,gE(gI),0,1,0.3,0.4,感染母猪,感染仔猪,阳性,阴性,24681012141618202224,抗体水平,什么时候感染？,?,+,感染,gE(gI),0,1,0.3,0.4,感染母猪,感染仔猪,阳性,阴性,24681012141618202224,抗体水平,周龄,什么时候打疫苗？,打疫苗,gE(gI),IntheFaceofanOutbreak爆发时,Anaccuratediagnosisisessential.必需进行急性