FelineInfectiousKatrin ilianUniversityMunich,BSH,11months,male英國短毛貓，11presenting ints-morequietsince3weeks,nowvery -intermittendfever,weightloss,thoracicWhatis什么是felineinfectiousperitonitisWhatis什么是felineinfectiousperitonitis(FIP)causedbyafelinecorona feline l 貓傳染性腹膜 Herreweghetal.,Whatis什么是felineinfectiousperitonitis(FIP)causedbyafelinecorona feline l 貓傳染性腹膜 Herreweghetal.,Whatis什么是felineinfectiousperitonitis(FIP)causedbyafelinecorona feline l 貓傳染性腹膜 Herreweghetal.,HypothesesconcerningtheoriginofFIP有關 的假?internalmutationhypothesis內部變異假說2 es2種循feline l Hypothesesconcerning?internalmutationhypothesis““內部變異假說”2circulating es2種循環feline l (FIPV) Hypothesesconcerning?internalmutationhypothesis““內部變異假說”2circulating es2種循環feline l (FIPV) replicationofFCoVinenterocytesFCoVmutation(s)inthe3C- =>FCoVcannotbinditselftothereceptorsonthe =>FCoV自身不能與腸細胞上的 incorporatedbymacrophages由巨噬細胞吞=>multipliesinmacrophages!在巨噬細胞中繁New?mutation-PCRMutationinnucleotid In e-proteinintheepitopeforthefusionofincatswithFIP發生FIP=>butnotincatswith l In120catswithFIP:在120只患有FIP 110showthismutationM 5showasimilarmutation(S-5showadifferentmutationWhydoonlysomecatsdevelop為什么僅有一部分貓會發展出傳染性腹膜炎increased =>increasedriskofmutation增加 factorsinfluencingreplication影 -young 遺傳傾向性（貓白細胞抗原復合物virulenceof 毒amount re-infectionrateinmultiplecat Howimportantisfelineinfectiousperitonitis(FIP)貓傳染性腹膜commondisease常見疾 y1ofeverynewfelinecasespresentedtoRohrbachetal., diagnosisofdiagnosisofBSH,11months,malepresenting ints主morequietsince3weeks,nowvery持續3周過分安靜，現在非常嗜intermittendfever,weightloss,thoraciclaboratory CBC/serumchemistry全血細胞計數 生 ysis滲出液的分 antibodydetectionblood血effusion滲出CSF腦脊blood血effusion滲出CSF腦脊feces排泄antigenantibodycomplexantigendetectioneffusion滲出tissue組織Histology

diagnosisofRetrospectivestudy(1979–488catswithFIP488只患傳染性腹膜炎的貓diagnosisconfirmedbyhistopatholog通過組織病理學確

Hartmannetal.,Retrospectivestudy(1979–488catswithFIP488只患傳染性腹膜炎的貓diagnosisconfirmedbyhistopatholog通過組織病理學確controlgroups(630cats對照組（630只貓

Hartmannetal., edtohaveFIP(otherdiagnosis疑似傳染性腹膜炎的貓（其他方法確診catswitheffusion有滲出的貓catswithotherdiseases其他疾病的

FIPprevalence0.51FIP發生率為0.51catswithouteffusion無滲出的貓(342)FIPprevalenceFIP發生率有catswithotherdiseases其他疾病的

laboratory CBC/serumchemistry全血細胞計數 生 ysis滲出液的分 antibodydetectionblood血effusion滲出CSF腦脊blood血effusion滲出CSF腦脊feces排泄antigenantibodycomplexantigendetectioneffusion滲出tissue組織Histology

diagnosisof Ascites腹ThoraciceffusionThoraciceffusionThoraciceffusionRenal?granulomas“腎臟“肉芽腫Intestinal?granulomas“腸道“肉芽腫Effusionsincats(n=0

thorax+

heartfailurebacterialserositisHirschberger,Hartmann,etal.,laboratory CBC/serumchemistry全血細胞計數 生 ysis滲出液分 antibodydetectionblood血effusion滲出CSF腦脊blood血effusion滲出CSF腦脊feces排泄antigenantibodycomplexantigendetectioneffusion滲出Histology

diagnosisofFIPCBC/serum -enzymes,electrolytes,Electrophoresis電-globulins球蛋albumin/globulinratioCBC/serum bloodcellcounts血細胞計not

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

p<g/dl4g/dl43210other其他疾laboratory CBC/serumchemistry全血細胞計數 生 ysis滲出液分 antibodydetectionblood血effusion滲出CSF腦脊blood血effusion滲出CSF腦脊feces排泄antigenantibodycomplexantigendetectioneffusion滲出tissue組織Histology

diagnosisof ParametersinefusionRivalta’s 他試抗貓冠 抗- antigenin巨噬細胞中的冠 抗cellcounts細胞計enzymeactivities酶活Cytology細胞Rivalta‘s useatesttube用一個試fillwithaquadest加滿蒸餾水-add1dropaceticacid(96加入一滴96%醋Mix混add1dropaspirateRivalta‘s useatesttube用一個試fillwithaquadest加滿蒸餾水-add1dropaceticacid(96加入一滴96%醋Mix混add1dropaspirate

dropdropremains,液滴存在fallsdownslowly緩慢下降Rivalta‘s Rivalta‘s Rivalta‘s NewstudyconcerningRivalta‘s retrospectivestudyinclusioncriteriadataof782catswith782只患有滲出液的貓的數patientsoftheSmallAnimalClinicfrom19992010從1999clearlyRivalta-positive明確 ?=>496ofthesewithadefinitive?其中的496etal.,inNewstudyconcerningRivalta‘s nnnRivaltaRivaltasensitivity敏感性91,3 預測值93,4%

specificity特異性65,5PPW陽性預測值Prevalence發生率34,6etal., highproteinlevel(50350mg/dlpleocytosis細胞增多(10010000nuclearmacrophages巨噬細胞laboratory CBC/serumchemistry全血細胞計數 生 ysis滲出液的分 antibodydetectionblood血effusion滲出CSF腦脊blood血effusion滲出CSF腦脊feces排泄antigenantibodycomplexantigendetectioneffusion滲出tissue組織Histology

diagnosisofAnti-FCoVantibodiesin IsthereanyvalueofantibodymeasurementatHowvaluableisaantibodyresulttorule-outIsthehighesttitervaluableinaclinicalsetting?

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

n=Hartmannetal.,laboratory CBC/serumchemistry全血細胞計數 生 ysis滲出液的分 antibodydetectionblood血effusion滲出CSF腦脊blood血effusion滲出CSF腦脊feces排泄antigenantibodycomplexantigendetectioneffusion滲出tissue組織Histology

diagnosisofFCoVPCRin血液貓冠 nestedRT-PCR巢式反轉錄--primersofthehighlyconserved3’-UTR用高度穩定的3’-UTR-177basepairsequencedescribedHerreweghetal.,FCoVPCRinblood血液貓冠 neg.predictivepos.predictive840PCR

PCR

notFIPFIPn=Hartmannetal.,LongtermPCRstudy(12長期的PCR研究（12個月47catswithconfirmedFIP69healthycatsofendemic來自流行地區的69只健康家養 Gunn-Mooreetal., 80%viremic(PCRpositive)inboth兩組都存在 血癥（PCR陽性LongtermPCRstudy(12長期的PCR研究（12個月47catswithconfirmedFIP69healthycatsofendemic來自流行地區的69只健康家養 Gunn-Mooreetal., 80%viremic(PCRpositive)inboth兩組都存在 血癥（PCR陽性independentofhealthconditionLongtermPCRstudy(12長期的PCR研究（12個月47catswithconfirmedFIP69healthycatsofendemic來自流行地區的69只健康家養

Gunn-Mooreetal., 80%viremic(PCRpositive)inboth兩組都存在 血癥（PCR陽性independentofhealthconditionviremiadoesnotpredictdevelopmentofHypothesesconcerning?internalmutationhypothesis““內部突變假說”2circulating es2個循環feline l (FIPV) Hypothesesconcerning?internalmutationhypothesis““內部突變假說”2circulating es2個循環feline l (FIPV) replicationofFCoVinenterocytesFCoVmutation(s)inthe3C- 變=>FCoVcannotbinditselftothereceptorsonthe =>FCoV自身不能與腸細胞的受體結 incorporatedbymacrophages由巨噬細胞吞=>multipliesinmacrophages!在巨噬細胞中繁New?mutation-PCR“Mutationinnucleotid In e-proteinintheepitopeforthefusionof incatswithFIP發生FIP=>butnotincatswith l In120catswithFIP:在120只患有FIP 110showthismutationM 5showasimilarmutation(S-5showadifferent5只顯示不同的變New?mutation-PCR“ 95,5ofcatswith 95,5的貓患有oneofthetwoprovenmutations具有這兩個已證明突變中的一mutation-PCRis 變異PCR很有sensitivity敏感ascites(100%)betterBuffy sma,serum(60-70腹水（100%）比血液白細胞層測試好，血漿 （60-70healthycats健康20positiveinnormalPCR(Buffycoat)正常PCR20%陽性（血液白細胞層）nonepositiveinmutations-PCR沒有任何貓表現出突變位點PCR測試陽laboratory CBC/serumchemistry全血細胞計數 生 ysis滲出液的分 antibodydetectionblood血effusion滲出CSF腦脊blood血effusion滲出CSF腦脊feces排泄antigenantibodycomplexantigendetection抗原檢effusion滲出tissue組織Histology

diagnosisofFCoVantigeninmacrophages 抗（免疫熒光抗體測定-centrifugeaspirate(1500-spreadonaslide(thick涂片（厚層-fixateinacetoneat-20在零下20 stainwithanti-FITC使用結合異硫酸熒光素的貓冠狀usefluorescencemicroscope(450使用熒光顯微鏡（450x）Dr.Frost,Gie?en,FCoVantigeninmacrophages巨噬細胞中的貓冠 neg.predictivepos.predictive0antigen

antigen

notFIPFIPnHartmannetal.,laboratory CBC/serumchemistry全血細胞計數 生 ysis滲出液的分 antibodydetectionblood血effusion滲出CSF腦脊blood血effusion滲出CSF腦脊feces排泄antigenantibodycomplexantigendetection抗原檢effusion滲出tissue組織Histology

diagnosisofImmunohistochemistryimmunohistochemistrystainingofFCoVantigenintissuemacrophages FCoVantigenonlyinmacrophagesincatswithFIP Tammeretal.,Picture:Prof.Reinacher,laboratory CBC/serumchemistry全血細胞計數 生 ysis滲出液的分 antibodydetectionblood血effusion滲出CSF腦脊blood血effusion滲出CSF腦脊feces排泄antigenantibodycomplexantigendetectioneffusion滲出tissue組織Histology組織學檢

diagnosisofoftenvasculitisand血管炎及血neutrophilslymphocytes淋巴細smacells漿細macrophages巨噬細thickened增厚的內皮組serofibrinous漿液纖維蛋白性的滲Picture:Prof.Reinacher,diagnosisofFIPincatswithinmostcasesfastandeasy-Rivalta’stestveryusefultestindiagnosiscanbeconfirmedbyantigendetectionConclusions總diagnosisofFIPincatswithout沒有滲出液的貓傳染性腹膜炎的診canbeextremelychallenging可能極 noneoftestsinbloodreliableweightedscoringsystem-onlyscoreofdefinitiveonlywithhistologyand/orImportanttoremember重要的是Importanttoremember重要的是firststepifFIP isthereyes

effusion滲出Rivalta‘s antigenmacrophages巨噬細胞中的lookfor

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treatmentoftreatmentofBSH,11months,male英國短毛貓，11個月，雄presenting intsmorequietsince3weeks,nowvery持續3周過于安靜，現在有點非常嗜intermittendfever,weightloss,thoracicBSH,11months,male英國短毛貓，11個月，雄presenting intsmorequietsince3weeks,nowvery持續3周過于安靜，現在有點嗜intermittendfever,weightloss,thoracic間歇性地發熱，體重下降，有胸Whatwouldthenextdiagnostic下一步診斷計劃是什么BSH,11months,male英國短毛貓，11個月，雄presenting intsmorequietsince3weeks,nowvery持續3周過于安靜，現在有點嗜intermittendfever,weightloss,thoracicBSH,11months,male英國短毛貓，11個月，雄presenting intsmorequietsince3weeks,nowvery持續3周過于安靜，現在有點嗜intermittendfever,weightloss,thoraciceffusion滲出-RivaltaBSH,11months,male英國短毛貓，11個月，雄presenting intsmorequietsince3weeks,nowvery持續3周過于安靜，現在有點嗜intermittendfever,weightloss,thoracicBSH,11months,male英國短毛貓，11個月，雄presenting intsmorequietsince3weeks,nowvery持續3周過于安靜，現在有點嗜intermittendfever,weightloss,thoraciceffusion滲出Rivalta positiveonIFBSH,11months,male英國短毛貓，11個月，雄presenting intsmorequietsince3weeks,nowvery持續3周過于安靜，現在有點嗜intermittendfever,weightloss,thoracicdiagnosis確診為貓傳染性腹膜FIP…isthereanyeffectiveGlucocorticoidswitheffusionwithdraweffusion,Dexamethasone1mg/kgq24hfor7 1mg/kgq24h連用7天intraperitonealorintrathoracicwithouteffusionPrednisolone2mg/kgp.o.q24龍2mg/kgp.oq24etal.,n>tMadewelletal.,Fordetal.,Bilkei,Hayes,Weissetal.,Weissetal.,Changetal.,B?lcskei&Bilkei,B?lcskei&Bilkei,Watarietal.,Ishidaetal.,Puttner,n>tMadewelletal.,Fordetal.,Bilkei,XHayes,Weissetal.,XXXWeissetal.,XXChangetal.,XXB?lcskei&Bilkei,XXB?lcskei&Bilkei,XXWatarietal.,Ishidaetal.,Puttner,causalmedicationsforFIPantiviraltherapy RibavirinhumanInterferon-α人干擾素felineInterferon-ω貓干擾素PropionibacteriumacnesPolyprenyl-immunostimulatingagent聚丙烯-inhibitionofthevasculitisInterferon-ω干擾素-ωIshidaetal.,Interferon-ω干擾素-ωtreatmentof12cats治療1felineinterferon-ω貓干擾glucocorticoids糖皮質類固Ishidaetal.,Interferon-ω干擾素-ωtreatmentof12cats治療1felineinterferon-ω貓干擾glucocorticoids糖皮質類固nocontrolgroupIshidaetal.,Interferon-ω干擾素-ωtreatmentof12cats治療1felineinterferon-ω貓干擾glucocorticoids糖皮質類固nocontrolgroupFIPnotconfirmed并沒有確診為Ishidaetal.,Interferon-ω干擾素-ωtreatmentof12cats治療1felineinterferon-ω貓干擾glucocorticoids糖皮質類固nocontrolgroupFIPnotconfirmed并沒有確診為4catssurvived2yearsIshidaetal.,FelineIFN-ω:field貓干擾素-ωcebo-controlleddouble-blindstudy安慰劑-36catswithFIP36FIPconfirmedbyhistologyand/ordetectionofFCoV-antigenin使用組織學和/或者巨噬細胞中FCoV抗原探測有確診（免疫組化/免疫熒19catswithInterferon-ω106IU/kgs.c.q24h7days,19只貓用干擾素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，連用7或 龍2mg/kgp.o.q24

Ritzetal.,Survivalcurvenosignificantdifference(p0.629)沒有明顯差 0

AlternativeTreatmentPolyprenylImmunostimulantpolyprenyl,PI(e.g.,Sass&Sassphosphorylatedpolyprenylwith10-14prenyl聚丙烯，聚戊烯醇磷酸酯會有10-14investigationalveterinarybiologicamixtureofphosphorylated,linearupregulationofbiosynthesisofmRNAofTh-1alsoantiviralandanti-tumor Polyprenylcaseseries3catswithFIP(withoutonecatsurvived14months一只存活14atnecropsyFIPonecatstillalive ngwellafter24一只貓仍然存活，24個月之后仍然狀況良immunohistochemistrystainingofFCoVantigen onecatstillalive ngwellafter28一只貓仍然存活，28個月之后良?asi9diagnosisPropentophylline己酮propentophylline(Karsivan?)forthetreatmentof=>longersurvivaltimesofcatswithfewcasereports少量的病例 (Trental?)=>positiveeffect己酮可可堿=》可能有效onsurvivaltimeandqualityofNorris,2007;Scherk,2007;Little,2005;Pedersen,modeofactiondecreaseoffibrinogen,cytokines,e.g.TNF-Propentophylline:Fieldcebocontrolleddoubleblinded有安慰劑對照的雙盲confirmedbyhistologyand/ordetectionofFCoV-antigeneinmacrophages(immunohistochemistry/immunofluorescence)、 7catspropentophylline18–25mg/kgPOq12h716 7只貓運用己酮可可堿1825mg/kgPOq12h716只貓運用symptomatictherapyandcorticosteroidsforall對所有的貓進行皮質witheffusion:dexamethasone1mg/kgIP/ITq24h7dalternativelyprednisolone2mg/kgPOq24h 1mg/kgIP/ITq24h7d或者運 龍2kgPOq24

etal.,Propentophylline:Fieldmediansurvivaltime:8(4–36)平均存活時間：8propentophylline:8,0cebo:7,5安慰劑：7,5

p=Propentophylline:Fieldmediansurvivaltime:8(4–36)平均存活時間：8propentophylline:8,0cebo:7,5安慰劑：7,5

p=nonoinotherparameters(incl.TNF-α)BSH,11months,male英國短毛貓，11個月，雄presenting intsmorequietsince3weeks,nowveryintermittendfever,weightloss,thoracicBSH,11months,male英國短毛貓，11個月，雄presenting intsmorequietsince3weeks,nowveryintermittendfever,weightloss,thoracicinterferon-ωωBSH,11months,male英國短毛貓，11個月，雄presenting intsmorequietsince3weeks,nowvery持續3周過于安靜，現在有點嗜intermittendfever,weightloss,thoracicduringtreatment治療期nomoregoodgeneralconditionweightgainafter6monthsupperrespiratorydiseaseprogressivedeteriorationanorexia,lethargy,signsof Uveitiseuthanasiaafter200daysafter6monthsupperrespiratorydiseaseprogressivedeteriorationanorexia,lethargy,signsof Uveitiseuthanasiaafter200daysnecropsy尸體剖檢WhydidJeffersonlive為什么Jefferson存活的更WhydidJeffersonlive為什么Jefferson存活的更WhydidJeffersonlive為什么Jefferson存活的更geneticdifferencesofthecat?貓 不同WhydidJeffersonlive為什么Jefferson存活的更geneticdifferencesofthecat?貓 不同differencesoftheFCoV?貓冠 的不同WhydidJeffersonlive為什么Jefferson存活的更geneticdifferencesofthecat?貓 不同differencesoftheFCoV?貓冠 的不同Treatment治WhydidJeffersonlive為什么Jefferson存活的更geneticdifferencesofthecat?貓 不同differencesoftheFCoV?貓冠 的不同Treatment治timepointoftreatment?WhydidJeffersonlive為什么Jefferson存活的更geneticdifferencesofthecat?貓 不同differencesoftheFCoV?貓冠 的不同Treatment治timepointoftreatment?drugsusedPrognosticTreatmentofHowdowedecide,whichcattotreatandwhichcattoeuthanize? Prognosticparameterswithstatisticallyconfirmedprognosticvalue通過統計證實的具有預后價值的參數Karnofsky‘sscorehigher越高betterprognosis預后越好amountofeffusion滲出液的量(lessbetterprognosis預后越bilirubinvalue總膽紅素(lower約低betterprognosis預后越好etcount血小板計數(higher越高betterprognosis預后越好lymphocytecount(higher越高betterprognosis預后EfficacyofExperimentalstudiesGerber,1995Hoskinsetal.,1995McArdleetal.,1995Scott,1995

efficacyof5075noefficacy沒有效果FieldstudiesFehretal.,1995PostorinoReeves,1995

vagueprotection保護力不明確nonegativereactions,noADEFieldstudiesin

Fehretal.,Incatsinmulti-cat-householdsNoeffectIncatswithoutpreviousexposuretoFCoV(noantibodies)significantdifferenceFIPin11ofapprox.500ofthecontrol近500個對照組中有11例FIPin7ofapprox.500ofthevaccinated近500個免疫組中有7例onlyuptoacertainonlyifnootherformercontactto onlyuptoacertainonlyifnootherformercontactto PreventingFIP預防PreventionofFCoV-infectionsin預防貓舍中FCoV傳Minimalizetheriskoftransmitting =>but...FCoVexistsinevery但是。。。FCoV存在于每個貓Controllingthedevelopmentof控制FIP的發ReductionofpredisposingWhyisFIPmainlyinmulti-cat-為什么FIP主要發生于多貓生活dose 劑FCoVinextremehighdosesinthefecesArisestypicallyinstressing在應激的情況下顯著升newsurroundings新環overcrowding擁highnoiselevel高噪otherillnesses其他疾FCoV-dynamicsinFCoVin(all)catteriesendemicFCoV80–90%ofcatsincatteriesareantibody-antibodytitercorrelateswithexcretion excretors慢性排毒者1020 excretion(?immune （