兽医师猫传染病专题中文6fip esavs katrin

FelineInfectiousKatrin ilianUniversityMunich,BSH,11months,male英国短毛猫，11presenting ints-morequietsince3weeks,nowvery -intermittendfever,weightloss,thoracicWhatis什么是felineinfectiousperitonitisWhatis什么是felineinfectiousperitonitis(FIP)causedbyafelinecorona feline l 猫传染性腹膜 Herreweghetal.,Whatis什么是felineinfectiousperitonitis(FIP)causedbyafelinecorona feline l 猫传染性腹膜 Herreweghetal.,Whatis什么是felineinfectiousperitonitis(FIP)causedbyafelinecorona feline l 猫传染性腹膜 Herreweghetal.,HypothesesconcerningtheoriginofFIP有关 的假„internalmutationhypothesis内部变异假说2 es2种循feline l Hypothesesconcerning„internalmutationhypothesis““内部变异假说”2circulating es2种循环feline l (FIPV) Hypothesesconcerning„internalmutationhypothesis““内部变异假说”2circulating es2种循环feline l (FIPV) replicationofFCoVinenterocytesFCoVmutation(s)inthe3C- =>FCoVcannotbinditselftothereceptorsonthe =>FCoV自身不能与肠细胞上的 incorporatedbymacrophages由巨噬细胞吞=>multipliesinmacrophages!在巨噬细胞中繁New„mutation-PCRMutationinnucleotid In e-proteinintheepitopeforthefusionofincatswithFIP发生FIP=>butnotincatswith l In120catswithFIP:在120只患有FIP 110showthismutationM 5showasimilarmutation(S-5showadifferentmutationWhydoonlysomecatsdevelop为什么仅有一部分猫会发展出传染性腹膜炎increased =>increasedriskofmutation增加 factorsinfluencingreplication影 -young 遗传倾向性（猫白细胞抗原复合物virulenceof 毒amount re-infectionrateinmultiplecat Howimportantisfelineinfectiousperitonitis(FIP)猫传染性腹膜commondisease常见疾 y1ofeverynewfelinecasespresentedtoRohrbachetal., diagnosisofdiagnosisofBSH,11months,malepresenting ints主morequietsince3weeks,nowvery持续3周过分安静，现在非常嗜intermittendfever,weightloss,thoraciclaboratory CBC/serumchemistry全血细胞计数 生 ysis渗出液的分 antibodydetectionblood血effusion渗出CSF脑脊blood血effusion渗出CSF脑脊feces排泄antigenantibodycomplexantigendetectioneffusion渗出tissue组织Histology

diagnosisofRetrospectivestudy(1979–488catswithFIP488只患传染性腹膜炎的猫diagnosisconfirmedbyhistopatholog通过组织病理学确

Hartmannetal.,Retrospectivestudy(1979–488catswithFIP488只患传染性腹膜炎的猫diagnosisconfirmedbyhistopatholog通过组织病理学确controlgroups(630cats对照组（630只猫

Hartmannetal., edtohaveFIP(otherdiagnosis疑似传染性腹膜炎的猫（其他方法确诊catswitheffusion有渗出的猫catswithotherdiseases其他疾病的

FIPprevalence0.51FIP发生率为0.51catswithouteffusion无渗出的猫(342)FIPprevalenceFIP发生率有catswithotherdiseases其他疾病的

laboratory CBC/serumchemistry全血细胞计数 生 ysis渗出液的分 antibodydetectionblood血effusion渗出CSF脑脊blood血effusion渗出CSF脑脊feces排泄antigenantibodycomplexantigendetectioneffusion渗出tissue组织Histology

diagnosisof Ascites腹ThoraciceffusionThoraciceffusionThoraciceffusionRenal„granulomas“肾脏“肉芽肿Intestinal„granulomas“肠道“肉芽肿Effusionsincats(n=0

thorax+

heartfailurebacterialserositisHirschberger,Hartmann,etal.,laboratory CBC/serumchemistry全血细胞计数 生 ysis渗出液分 antibodydetectionblood血effusion渗出CSF脑脊blood血effusion渗出CSF脑脊feces排泄antigenantibodycomplexantigendetectioneffusion渗出Histology

diagnosisofFIPCBC/serum -enzymes,electrolytes,Electrophoresis电-globulins球蛋albumin/globulinratioCBC/serum bloodcellcounts血细胞计not

-enzymes,electrolytes,Electrophoresis电-globulins球蛋albumin/globulinratioAlbumin/globulinHartmannetal.,

p<g/dl4g/dl43210other其他疾laboratory CBC/serumchemistry全血细胞计数 生 ysis渗出液分 antibodydetectionblood血effusion渗出CSF脑脊blood血effusion渗出CSF脑脊feces排泄antigenantibodycomplexantigendetectioneffusion渗出tissue组织Histology

diagnosisof ParametersinefusionRivalta’s 他试抗猫冠 抗- antigenin巨噬细胞中的冠 抗cellcounts细胞计enzymeactivities酶活Cytology细胞Rivalta‘s useatesttube用一个试fillwithaquadest加满蒸馏水-add1dropaceticacid(96加入一滴96%醋Mix混add1dropaspirateRivalta‘s useatesttube用一个试fillwithaquadest加满蒸馏水-add1dropaceticacid(96加入一滴96%醋Mix混add1dropaspirate

dropdropremains,液滴存在fallsdownslowly缓慢下降Rivalta‘s Rivalta‘s Rivalta‘s NewstudyconcerningRivalta‘s retrospectivestudyinclusioncriteriadataof782catswith782只患有渗出液的猫的数patientsoftheSmallAnimalClinicfrom19992010从1999clearlyRivalta-positive明确 •=>496ofthesewithadefinitive•其中的496etal.,inNewstudyconcerningRivalta‘s nnnRivaltaRivaltasensitivity敏感性91,3 预测值93,4%

specificity特异性65,5PPW阳性预测值Prevalence发生率34,6etal., highproteinlevel(50350mg/dlpleocytosis细胞增多(10010000nuclearmacrophages巨噬细胞laboratory CBC/serumchemistry全血细胞计数 生 ysis渗出液的分 antibodydetectionblood血effusion渗出CSF脑脊blood血effusion渗出CSF脑脊feces排泄antigenantibodycomplexantigendetectioneffusion渗出tissue组织Histology

diagnosisofAnti-FCoVantibodiesin IsthereanyvalueofantibodymeasurementatHowvaluableisaantibodyresulttorule-outIsthehighesttitervaluableinaclinicalsetting?

Anti-FCoVantibodiesinblood(+/-n neg.predictivevalue预测ospredictivevaluepnotFIPpFIP0antibody antibody

n=Hartmannetal.,laboratory CBC/serumchemistry全血细胞计数 生 ysis渗出液的分 antibodydetectionblood血effusion渗出CSF脑脊blood血effusion渗出CSF脑脊feces排泄antigenantibodycomplexantigendetectioneffusion渗出tissue组织Histology

diagnosisofFCoVPCRin血液猫冠 nestedRT-PCR巢式反转录--primersofthehighlyconserved3’-UTR用高度稳定的3’-UTR-177basepairsequencedescribedHerreweghetal.,FCoVPCRinblood血液猫冠 neg.predictivepos.predictive840PCR

PCR

notFIPFIPn=Hartmannetal.,LongtermPCRstudy(12长期的PCR研究（12个月47catswithconfirmedFIP69healthycatsofendemic来自流行地区的69只健康家养 Gunn-Mooreetal., 80%viremic(PCRpositive)inboth两组都存在 血症（PCR阳性LongtermPCRstudy(12长期的PCR研究（12个月47catswithconfirmedFIP69healthycatsofendemic来自流行地区的69只健康家养 Gunn-Mooreetal., 80%viremic(PCRpositive)inboth两组都存在 血症（PCR阳性independentofhealthconditionLongtermPCRstudy(12长期的PCR研究（12个月47catswithconfirmedFIP69healthycatsofendemic来自流行地区的69只健康家养

Gunn-Mooreetal., 80%viremic(PCRpositive)inboth两组都存在 血症（PCR阳性independentofhealthconditionviremiadoesnotpredictdevelopmentofHypothesesconcerning„internalmutationhypothesis““内部突变假说”2circulating es2个循环feline l (FIPV) Hypothesesconcerning„internalmutationhypothesis““内部突变假说”2circulating es2个循环feline l (FIPV) replicationofFCoVinenterocytesFCoVmutation(s)inthe3C- 变=>FCoVcannotbinditselftothereceptorsonthe =>FCoV自身不能与肠细胞的受体结 incorporatedbymacrophages由巨噬细胞吞=>multipliesinmacrophages!在巨噬细胞中繁New„mutation-PCR“Mutationinnucleotid In e-proteinintheepitopeforthefusionof incatswithFIP发生FIP=>butnotincatswith l In120catswithFIP:在120只患有FIP 110showthismutationM 5showasimilarmutation(S-5showadifferent5只显示不同的变New„mutation-PCR“ 95,5ofcatswith 95,5的猫患有oneofthetwoprovenmutations具有这两个已证明突变中的一mutation-PCRis 变异PCR很有sensitivity敏感ascites(100%)betterBuffy sma,serum(60-70腹水（100%）比血液白细胞层测试好，血浆 （60-70healthycats健康20positiveinnormalPCR(Buffycoat)正常PCR20%阳性（血液白细胞层）nonepositiveinmutations-PCR没有任何猫表现出突变位点PCR测试阳laboratory CBC/serumchemistry全血细胞计数 生 ysis渗出液的分 antibodydetectionblood血effusion渗出CSF脑脊blood血effusion渗出CSF脑脊feces排泄antigenantibodycomplexantigendetection抗原检effusion渗出tissue组织Histology

diagnosisofFCoVantigeninmacrophages 抗（免疫荧光抗体测定-centrifugeaspirate(1500-spreadonaslide(thick涂片（厚层-fixateinacetoneat-20在零下20 stainwithanti-FITC使用结合异硫酸荧光素的猫冠状usefluorescencemicroscope(450使用荧光显微镜（450x）Dr.Frost,Gießen,FCoVantigeninmacrophages巨噬细胞中的猫冠 neg.predictivepos.predictive0antigen

antigen

notFIPFIPnHartmannetal.,laboratory CBC/serumchemistry全血细胞计数 生 ysis渗出液的分 antibodydetectionblood血effusion渗出CSF脑脊blood血effusion渗出CSF脑脊feces排泄antigenantibodycomplexantigendetection抗原检effusion渗出tissue组织Histology

diagnosisofImmunohistochemistryimmunohistochemistrystainingofFCoVantigenintissuemacrophages FCoVantigenonlyinmacrophagesincatswithFIP Tammeretal.,Picture:Prof.Reinacher,laboratory CBC/serumchemistry全血细胞计数 生 ysis渗出液的分 antibodydetectionblood血effusion渗出CSF脑脊blood血effusion渗出CSF脑脊feces排泄antigenantibodycomplexantigendetectioneffusion渗出tissue组织Histology组织学检

diagnosisofoftenvasculitisand血管炎及血neutrophilslymphocytes淋巴细smacells浆细macrophages巨噬细thickened增厚的内皮组serofibrinous浆液纤维蛋白性的渗Picture:Prof.Reinacher,diagnosisofFIPincatswithinmostcasesfastandeasy-Rivalta’stestveryusefultestindiagnosiscanbeconfirmedbyantigendetectionConclusions总diagnosisofFIPincatswithout没有渗出液的猫传染性腹膜炎的诊canbeextremelychallenging可能极 noneoftestsinbloodreliableweightedscoringsystem-onlyscoreofdefinitiveonlywithhistologyand/orImportanttoremember重要的是Importanttoremember重要的是firststepifFIP isthereyes

effusion渗出Rivalta‘s antigenmacrophages巨噬细胞中的lookfor

„mutationPCR突变位点

lookforother

exploratory+

not

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lookfor

treatmentoftreatmentofBSH,11months,male英国短毛猫，11个月，雄presenting intsmorequietsince3weeks,nowvery持续3周过于安静，现在有点非常嗜intermittendfever,weightloss,thoracicBSH,11months,male英国短毛猫，11个月，雄presenting intsmorequietsince3weeks,nowvery持续3周过于安静，现在有点嗜intermittendfever,weightloss,thoracic间歇性地发热，体重下降，有胸Whatwouldthenextdiagnostic下一步诊断计划是什么BSH,11months,male英国短毛猫，11个月，雄presenting intsmorequietsince3weeks,nowvery持续3周过于安静，现在有点嗜intermittendfever,weightloss,thoracicBSH,11months,male英国短毛猫，11个月，雄presenting intsmorequietsince3weeks,nowvery持续3周过于安静，现在有点嗜intermittendfever,weightloss,thoraciceffusion渗出-RivaltaBSH,11months,male英国短毛猫，11个月，雄presenting intsmorequietsince3weeks,nowvery持续3周过于安静，现在有点嗜intermittendfever,weightloss,thoracicBSH,11months,male英国短毛猫，11个月，雄presenting intsmorequietsince3weeks,nowvery持续3周过于安静，现在有点嗜intermittendfever,weightloss,thoraciceffusion渗出Rivalta positiveonIFBSH,11months,male英国短毛猫，11个月，雄presenting intsmorequietsince3weeks,nowvery持续3周过于安静，现在有点嗜intermittendfever,weightloss,thoracicdiagnosis确诊为猫传染性腹膜FIP…isthereanyeffectiveGlucocorticoidswitheffusionwithdraweffusion,Dexamethasone1mg/kgq24hfor7 1mg/kgq24h连用7天intraperitonealorintrathoracicwithouteffusionPrednisolone2mg/kgp.o.q24龙2mg/kgp.oq24etal.,n>tMadewelletal.,Fordetal.,Bilkei,Hayes,Weissetal.,Weissetal.,Changetal.,Bölcskei&Bilkei,Bölcskei&Bilkei,Watarietal.,Ishidaetal.,Puttner,n>tMadewelletal.,Fordetal.,Bilkei,XHayes,Weissetal.,XXXWeissetal.,XXChangetal.,XXBölcskei&Bilkei,XXBölcskei&Bilkei,XXWatarietal.,Ishidaetal.,Puttner,causalmedicationsforFIPantiviraltherapy RibavirinhumanInterferon-α人干扰素felineInterferon-ω猫干扰素PropionibacteriumacnesPolyprenyl-immunostimulatingagent聚丙烯-inhibitionofthevasculitisInterferon-ω干扰素-ωIshidaetal.,Interferon-ω干扰素-ωtreatmentof12cats治疗1felineinterferon-ω猫干扰glucocorticoids糖皮质类固Ishidaetal.,Interferon-ω干扰素-ωtreatmentof12cats治疗1felineinterferon-ω猫干扰glucocorticoids糖皮质类固nocontrolgroupIshidaetal.,Interferon-ω干扰素-ωtreatmentof12cats治疗1felineinterferon-ω猫干扰glucocorticoids糖皮质类固nocontrolgroupFIPnotconfirmed并没有确诊为Ishidaetal.,Interferon-ω干扰素-ωtreatmentof12cats治疗1felineinterferon-ω猫干扰glucocorticoids糖皮质类固nocontrolgroupFIPnotconfirmed并没有确诊为4catssurvived2yearsIshidaetal.,FelineIFN-ω:field猫干扰素-ωcebo-controlleddouble-blindstudy安慰剂-36catswithFIP36FIPconfirmedbyhistologyand/ordetectionofFCoV-antigenin使用组织学和/或者巨噬细胞中FCoV抗原探测有确诊（免疫组化/免疫荧19catswithInterferon-ω106IU/kgs.c.q24h7days,19只猫用干扰素ω，106IU/kgs.c.q24h，用7天,thenonceaweek之后每周一次17cats Symptomatictherapyandglucocorticoidsforallwitheffusion:Dexamethasone1mg/kgi.p./i.t.q24hfor7alternativelyPrednisolone2mg/kgp.o.q24h 1mg/kgi.p./i.t.q24h，连用7或 龙2mg/kgp.o.q24

Ritzetal.,Survivalcurvenosignificantdifference(p0.629)没有明显差 0

AlternativeTreatmentPolyprenylImmunostimulantpolyprenyl,PI(e.g.,Sass&Sassphosphorylatedpolyprenylwith10-14prenyl聚丙烯，聚戊烯醇磷酸酯会有10-14investigationalveterinarybiologicamixtureofphosphorylated,linearupregulationofbiosynthesisofmRNAofTh-1alsoantiviralandanti-tumor Polyprenylcaseseries3catswithFIP(withoutonecatsurvived14months一只存活14atnecropsyFIPonecatstillalive ngwellafter24一只猫仍然存活，24个月之后仍然状况良immunohistochemistrystainingofFCoVantigen onecatstillalive ngwellafter28一只猫仍然存活，28个月之后良•asi9diagnosisPropentophylline己酮propentophylline(Karsivan®)forthetreatmentof=>longersurvivaltimesofcatswithfewcasereports少量的病例 (Trental®)=>positiveeffect己酮可可碱=》可能有效onsurvivaltimeandqualityofNorris,2007;Scherk,2007;Little,2005;Pedersen,modeofactiondecreaseoffibrinogen,cytokines,e.g.TNF-Propentophylline:Fieldcebocontrolleddoubleblinded有安慰剂对照的双盲confirmedbyhistologyand/ordetectionofFCoV-antigeneinmacrophages(immunohistochemistry/immunofluorescence)、 7catspropentophylline18–25mg/kgPOq12h716 7只猫运用己酮可可碱1825mg/kgPOq12h716只猫运用symptomatictherapyandcorticosteroidsforall对所有的猫进行皮质witheffusion:dexamethasone1mg/kgIP/ITq24h7dalternativelyprednisolone2mg/kgPOq24h 1mg/kgIP/ITq24h7d或者运 龙2kgPOq24

etal.,Propentophylline:Fieldmediansurvivaltime:8(4–36)平均存活时间：8propentophylline:8,0cebo:7,5安慰剂：7,5

p=Propentophylline:Fieldmediansurvivaltime:8(4–36)平均存活时间：8propentophylline:8,0cebo:7,5安慰剂：7,5

p=nonoinotherparameters(incl.TNF-α)BSH,11months,male英国短毛猫，11个月，雄presenting intsmorequietsince3weeks,nowveryintermittendfever,weightloss,thoracicBSH,11months,male英国短毛猫，11个月，雄presenting intsmorequietsince3weeks,nowveryintermittendfever,weightloss,thoracicinterferon-ωωBSH,11months,male英国短毛猫，11个月，雄presenting intsmorequietsince3weeks,nowvery持续3周过于安静，现在有点嗜intermittendfever,weightloss,thoracicduringtreatment治疗期nomoregoodgeneralconditionweightgainafter6monthsupperrespiratorydiseaseprogressivedeteriorationanorexia,lethargy,signsof Uveitiseuthanasiaafter200daysafter6monthsupperrespiratorydiseaseprogressivedeteriorationanorexia,lethargy,signsof Uveitiseuthanasiaafter200daysnecropsy尸体剖检WhydidJeffersonlive为什么Jefferson存活的更WhydidJeffersonlive为什么Jefferson存活的更WhydidJeffersonlive为什么Jefferson存活的更geneticdifferencesofthecat?猫 不同WhydidJeffersonlive为什么Jefferson存活的更geneticdifferencesofthecat?猫 不同differencesoftheFCoV?猫冠 的不同WhydidJeffersonlive为什么Jefferson存活的更geneticdifferencesofthecat?猫 不同differencesoftheFCoV?猫冠 的不同Treatment治WhydidJeffersonlive为什么Jefferson存活的更geneticdifferencesofthecat?猫 不同differencesoftheFCoV?猫冠 的不同Treatment治timepointoftreatment?WhydidJeffersonlive为什么Jefferson存活的更geneticdifferencesofthecat?猫 不同differencesoftheFCoV?猫冠 的不同Treatment治timepointoftreatment?drugsusedPrognosticTreatmentofHowdowedecide,whichcattotreatandwhichcattoeuthanize? Prognosticparameterswithstatisticallyconfirmedprognosticvalue通过统计证实的具有预后价值的参数Karnofsky‘sscorehigher越高betterprognosis预后越好amountofeffusion渗出液的量(lessbetterprognosis预后越bilirubinvalue总胆红素(lower约低betterprognosis预后越好etcount血小板计数(higher越高betterprognosis预后越好lymphocytecount(higher越高betterprognosis预后EfficacyofExperimentalstudiesGerber,1995Hoskinsetal.,1995McArdleetal.,1995Scott,1995

efficacyof5075noefficacy没有效果FieldstudiesFehretal.,1995PostorinoReeves,1995

vagueprotection保护力不明确nonegativereactions,noADEFieldstudiesin

Fehretal.,Incatsinmulti-cat-householdsNoeffectIncatswithoutpreviousexposuretoFCoV(noantibodies)significantdifferenceFIPin11ofapprox.500ofthecontrol近500个对照组中有11例FIPin7ofapprox.500ofthevaccinated近500个免疫组中有7例onlyuptoacertainonlyifnootherformercontactto onlyuptoacertainonlyifnootherformercontactto PreventingFIP预防PreventionofFCoV-infectionsin预防猫舍中FCoV传Minimalizetheriskoftransmitting =>but...FCoVexistsinevery但是。。。FCoV存在于每个猫Controllingthedevelopmentof控制FIP的发ReductionofpredisposingWhyisFIPmainlyinmulti-cat-为什么FIP主要发生于多猫生活dose 剂FCoVinextremehighdosesinthefecesArisestypicallyinstressing在应激的情况下显著升newsurroundings新环overcrowding拥highnoiselevel高噪otherillnesses其他疾FCoV-dynamicsinFCoVin(all)catteriesendemicFCoV80–90%ofcatsincatteriesareantibody-antibodytitercorrelateswithexcretion excretors慢性排毒者1020 excretion(„immune （