Boli Infectioase ale Boli Infectioase ale FelineFelinelorlor

Curs anul 5Curs anul 5

010091551263

PanleuPanleuccopeniaopenia Felina Felina- - DefinitieDefinitie--

Boala virala, sBoala virala, severeveraa, , deosebit de deosebit de contagioasacontagioasa, , a pisicilor tinere nevaccinate, a pisicilor tinere nevaccinate, clinic insotita de simptomatologie clinic insotita de simptomatologie gastrointestinalgastrointestinala.a.

Cea mai importanta boala a efectivelor de Cea mai importanta boala a efectivelor de pisici pisici nnevaccinate.evaccinate.

Rata de infectie a felinelor receptiveRata de infectie a felinelor receptive= 100%= 100% LeuLeuccopenia = openia = semn caracteristicsemn caracteristic MortalitMortalitate deate de = 25 – 90% = 25 – 90% Total control Total control numai prin vaccinarenumai prin vaccinare

PanleuPanleuccopeniaopenia Felina Felina IIstorstoricic

First described in 1800 as “cat First described in 1800 as “cat plague”plague”THETHE most important disease of most important disease of catscats

50-100% incidence in animal shelters50-100% incidence in animal sheltersMortality 25-90%Mortality 25-90%

First crude tissue origin vaccine in First crude tissue origin vaccine in 19341934Causative virus isolated & Causative virus isolated & identified in 1960sidentified in 1960sExcellent vaccines developed Excellent vaccines developed 1968-19751968-1975Vaccine programs centered Vaccine programs centered around FParound FP

Feline PanleukopeniaFeline PanleukopeniaCurrent StatusCurrent Status

Vaccines excellent Vaccines excellent – can totally control – can totally control and prevent FPand prevent FPIncidence very lowIncidence very lowStill problem in some populationsStill problem in some populations

SheltersSheltersFarmsFarmsFree-roaming cats/feral populationsFree-roaming cats/feral populations

Cause of problemsCause of problemsContaminated environmentContaminated environmentImproper or no vaccinationImproper or no vaccination

Canine parvovirus – some strains infect Canine parvovirus – some strains infect catscatsChange in revaccination Change in revaccination recommendationsrecommendations

Feline PanleukopeniaFeline PanleukopeniaSynonymsSynonyms

FPFPFPLFPLFeline parvovirus infectionFeline parvovirus infectionFPV infectionFPV infectionFeline “distemper”Feline “distemper”Feline infectious enteritisFeline infectious enteritisCat “plague”Cat “plague”Feline ataxiaFeline ataxiaFeline cerebellar hypoplasiaFeline cerebellar hypoplasia

FP ~ FP ~ EtiologyEtiology

Feline Parvovirus (FPV)Feline Parvovirus (FPV)Single serotypeSingle serotypeCross-reacts with CPV-2 & MEVCross-reacts with CPV-2 & MEV

Canine Parvovirus-2 (CPV-2)Canine Parvovirus-2 (CPV-2)CPV-2 - 1CPV-2 - 1stst appeared in dogs in 1977 appeared in dogs in 1977CPV-2a - dogs in 1978; can cause FP CPV-2a - dogs in 1978; can cause FP in catsin catsCPV-2b - dogs in 1984; can cause FP CPV-2b - dogs in 1984; can cause FP in catsin catsCPV-2c - large cats 1997; can cause CPV-2c - large cats 1997; can cause FP in catsFP in cats

Characteristics of FPVCharacteristics of FPV

ParvovirusParvovirus = small, single-stranded = small, single-stranded DNA virusDNA virusAbsolute need for Absolute need for mitotic cell mitotic cell for for replicationreplicationProduces intranuclear inclusionsProduces intranuclear inclusionsExtreme Extreme resistanceresistance

Will survive for years at room Will survive for years at room temperaturetemperatureResistant to most disinfectantsResistant to most disinfectants

Similar to CPV-2 and MEVSimilar to CPV-2 and MEV

FPV Intranuclear InclusionsFPV Intranuclear Inclusions~ Cell Culture ~~ Cell Culture ~

HostsHosts

FelidaeFelidaeDomestic cat = primary hostDomestic cat = primary hostNon-domestic felids – all believed to be Non-domestic felids – all believed to be susceptiblesusceptible

CanidaeCanidaeOutbreaks in dogs in EuropeOutbreaks in dogs in EuropeArtic foxArtic fox

ProcyonidaeProcyonidaeRaccoonRaccoonCoatimundiCoatimundi

MustelidaeMustelidaeMink – MEV, subclinical FPV infectionMink – MEV, subclinical FPV infectionOthers? – skunks, otters, weasels, badgersOthers? – skunks, otters, weasels, badgers

EpidemiologyEpidemiology

Distribution - worldwideDistribution - worldwideIncidenceIncidence

High in unvaccinated populationsHigh in unvaccinated populationsLow in properly vaccinated catsLow in properly vaccinated cats

Season Season Summer & Fall – susceptible kittensSummer & Fall – susceptible kittensCan occur throughout yearCan occur throughout year

AgeAgeKittens 2-4 months old most susceptibleKittens 2-4 months old most susceptibleAny age may be susceptibleAny age may be susceptible

Sex predilection - noneSex predilection - none

Transmission of FPVTransmission of FPV

Direct contactDirect contactContaminated environment & fomitesContaminated environment & fomites

Cages, floor, food dishes, water bowls, Cages, floor, food dishes, water bowls, beddingbedding

Contaminated hands, clothing, and feet Contaminated hands, clothing, and feet of peopleof peopleIn uteroIn utero infection – if queen has acute infection – if queen has acute infectioninfectionCarrier cats? – possible, but not Carrier cats? – possible, but not commoncommon

Pathogenesis of FPV Pathogenesis of FPV InfectionInfection

Virus requires a Virus requires a mitotic cellmitotic cell for for replication. All clinical signs result from replication. All clinical signs result from cytolysis of mitotic cellscytolysis of mitotic cells

Intestinal cryptsIntestinal cryptsVomiting & diarrheaVomiting & diarrheaDehydrationDehydration22ndnd bacterial infections bacterial infections

Lymphopoietic cellsLymphopoietic cellsPanleukopeniaPanleukopenia

Granulocyts & Purkinje cells of cerebellum Granulocyts & Purkinje cells of cerebellum (neonate)(neonate)

Cerebellar hypoplasiaCerebellar hypoplasiaRetina (neonate)Retina (neonate)

Retinal dysplasiaRetinal dysplasia

Feline PanleukopeniaFeline PanleukopeniaForms of DiseaseForms of Disease

Peracute FPPeracute FPAcute FP = typicalAcute FP = typicalMild FPMild FPSubclinical infectionSubclinical infection““Chronic” FPChronic” FPIn uteroIn utero infection infection

Feline PanleukopeniaFeline PanleukopeniaPeracute FPPeracute FP

Very acute onsetVery acute onsetCat may just disappear, found Cat may just disappear, found deaddeadSubnormal temperature, 94-98 F.Subnormal temperature, 94-98 F.Severe leukopeniaSevere leukopeniaSevere depressionSevere depressionOwner may believe cat was Owner may believe cat was poisonedpoisonedAlmost always fatal within 12 Almost always fatal within 12 hourshours

Feline PanleukopeniaFeline PanleukopeniaAcute or Typical FPAcute or Typical FP

FeverFeverMild to moderateMild to moderateMay have subnormal temp.May have subnormal temp.

DDepression - may be severeepression - may be severeClassic attitude or postureClassic attitude or posture

Vomiting and Vomiting and DDiarrheaiarrheaDDehydration - usually severeehydration - usually severeComplete anorexiaComplete anorexiaDDeatheath

Feline PanleukopeniaFeline PanleukopeniaMild FPMild FP

Slight anorexiaSlight anorexiaSlight feverSlight feverSome depressionSome depressionLeukopenia - only consistent Leukopenia - only consistent findingfindingPerhaps mild gastroenteritisPerhaps mild gastroenteritisWill recover without treatmentWill recover without treatment

Feline PanleukopeniaFeline PanleukopeniaSubclinical InfectionSubclinical Infection

More common in More common in older catsolder catsCat appears clinically normalCat appears clinically normalSlight feverSlight feverSlight leukopeniaSlight leukopeniaViremic and shedding virusViremic and shedding virusDevelops excellent immune Develops excellent immune responseresponse

Feline PanleukopeniaFeline Panleukopenia“Chronic” FP“Chronic” FP

Presents with “panleukopenia-Presents with “panleukopenia-like” syndromelike” syndromeChronic leukopeniaChronic leukopeniaChronic enteritisChronic enteritisChronic wastingChronic wastingHistopathology - enteric lesions Histopathology - enteric lesions like FPlike FPUsually this is Usually this is feline leukemiafeline leukemia, not , not FPFP

Feline PanleukopeniaFeline Panleukopenia“In utero” Infection“In utero” Infection

Usually with subclinical infection of Usually with subclinical infection of Ab(-) queenAb(-) queenOne or more fetuses may be One or more fetuses may be destroyeddestroyed

AbortionAbortionFetal resorptionFetal resorptionMummified fetusMummified fetusStillbirth, or “fading” newborn kittenStillbirth, or “fading” newborn kitten

Congenital birth defectsCongenital birth defectsCerebellar hypoplasia with ataxiaCerebellar hypoplasia with ataxiaRetinal dysplasiaRetinal dysplasiaHydrocephalusHydrocephalus

FP ~ FP ~ DiagnosisDiagnosis

HistoryHistoryClinical signsClinical signsLaboratory findingsLaboratory findings

Total leukocyte countTotal leukocyte countViral isolation/FPV antigen Viral isolation/FPV antigen detectiondetectionSerological findingsSerological findings

Postmortem findingsPostmortem findingsGross pathological changesGross pathological changesHistopathological changesHistopathological changes

FP ~ FP ~ Diagnosis - HistoryDiagnosis - History

Unvaccinated cat?Unvaccinated cat?Vaccinated under 14-16 weeks of Vaccinated under 14-16 weeks of age?age?Recent exposure?Recent exposure?Adoption shelter?Adoption shelter?Farm or feral cat?Farm or feral cat?

FP Diagnosis ~FP Diagnosis ~ Clinical Clinical SignsSigns

Sudden onsetSudden onsetFever, lethargy, depressionFever, lethargy, depressionClassic attitude or postureClassic attitude or posture

head down, shoulders elevated, tucked head down, shoulders elevated, tucked positionpositionhang head over food/water dishhang head over food/water dish

Diarrhea and vomitingDiarrhea and vomitingSevere dehydrationSevere dehydrationComplete anorexiaComplete anorexiaAbdominal palpationAbdominal palpation

edematous, turgid bowelsedematous, turgid bowelspain?pain?

FP – Classic AttitudeFP – Classic Attitude

FP Diagnosis ~FP Diagnosis ~ Laboratory Laboratory FindingsFindings

PanleukopeniaPanleukopenia4-8,000 cells/dl = mild or subclinical 4-8,000 cells/dl = mild or subclinical infectioninfection2-4,000 cells/dl = acute infection2-4,000 cells/dl = acute infection<2,000 cells/dl = acute or peracute infection<2,000 cells/dl = acute or peracute infection

Viral isolation/detectionViral isolation/detectionPositive canine parvovirus SNAP testPositive canine parvovirus SNAP test – feces – fecesIsolation from feces, ileum/jejunum, thymus, Isolation from feces, ileum/jejunum, thymus, spleenspleenPCRPCRImmunofluorescence (IFA) - ileumImmunofluorescence (IFA) - ileumElectron microscopy - identify viral particles Electron microscopy - identify viral particles in fecesin feces

Serum antibody titers Serum antibody titers 4-fold increase in paired serum samples4-fold increase in paired serum samples

Feline PanleukopeniaFeline PanleukopeniaLeukocyte Count vs. Clinical Leukocyte Count vs. Clinical

DiseaseDisease

Clinical DiseaseClinical Disease

01,0002,0003,0004,0005,0006,0007,0008,0009,000

10,000

Normal Mild Acute

High

Low

Feline PanleukopeniaFeline PanleukopeniaDiagnosis - Viral Diagnosis - Viral

DetectionDetection

Detect FPV or antigen in fecesDetect FPV or antigen in feces Canine parvovirus SNAP testCanine parvovirus SNAP test Electron microscopy for viral particlesElectron microscopy for viral particles

Viral isolation in cell culturesViral isolation in cell cultures Ileum, spleen, thymus, rectal swabIleum, spleen, thymus, rectal swab

IFA on tissues IFA on tissues Small intestine - ileum, jejunumSmall intestine - ileum, jejunum

PCRPCR

PanleukopeniaPanleukopeniaSerological AssaysSerological Assays

Virus neutralization (VN) assay Virus neutralization (VN) assay = serum neutralization (SN) assay= serum neutralization (SN) assay

ELISAELISA Paired serum samples:Paired serum samples:

2 weeks apart for diagnosis2 weeks apart for diagnosis 4-fold rise in titer4-fold rise in titer

Single serum sample to check Single serum sample to check immunity:immunity: Titer = 1:10 or higher if >16 weeks oldTiter = 1:10 or higher if >16 weeks old

Feline Panleukopenia Feline Panleukopenia DiagnosisDiagnosis

Gross Pathologic FindingsGross Pathologic FindingsRough hair coatRough hair coatGaunt and dehydratedGaunt and dehydratedEvidence of diarrhea and Evidence of diarrhea and vomitingvomitingGross pathological changes may Gross pathological changes may be mildbe mildThick, edematous walls of small Thick, edematous walls of small intestineintestineHyperemia, petechial or Hyperemia, petechial or ecchymotic ecchymotic hemorrhages - hemorrhages - jejunum & ileumjejunum & ileumSmall thymus in young kittensSmall thymus in young kittens

Small Intestine of Cat with FPSmall Intestine of Cat with FP

Small Intestine of Cat with FPSmall Intestine of Cat with FP

Lesions in Neonatal Kittens Lesions in Neonatal Kittens with Feline Panleukopeniawith Feline Panleukopenia

Thymic atrophyThymic atrophy Retinal dysplasiaRetinal dysplasia Cerebellar hypoplasiaCerebellar hypoplasia

Feline Panleukopenia DiagnosisFeline Panleukopenia DiagnosisHistopathologic FindingsHistopathologic Findings

Ileum & jejunumIleum & jejunumDilated crypts with loss of epithelium Dilated crypts with loss of epithelium Short, blunted, fused villiShort, blunted, fused villiPathognomonic lesionPathognomonic lesion

Lack of inflammatory cellsLack of inflammatory cellsIntranuclear inclusions early in Intranuclear inclusions early in diseasedisease

Jejunum - NormalJejunum - Normal

Panleukopenia ~ Panleukopenia ~ TreatmentTreatment

Supportive care Supportive care until immune responseuntil immune response FPV antiserum?FPV antiserum? Fluid and electrolyte replacementFluid and electrolyte replacement– Indwelling IV catheterIndwelling IV catheter

– Lactated Ringers with potassiumLactated Ringers with potassium

– 5% dextrose in electrolyte replacer5% dextrose in electrolyte replacer

– 60-100 ml/kg/hr60-100 ml/kg/hr

No antivirals against parvovirusNo antivirals against parvovirus GI therapyGI therapy Antibiotics parenterallyAntibiotics parenterally DietDiet

FP - Vaccines Available MLV vaccines

• Injectable vaccines• Intranasal vaccines

Inactivated vaccines• Injectable non-adjuvanted• Injectable adjuvanted

Recombinant FP vaccines - experimental

FP vaccines are often in combination JAVMA 229(9):1405-1441, 2006

Feline Vaccine Feline Vaccine RecommendationsRecommendations

Standard ConditionsStandard ConditionsFPV/FHV/FCVFPV/FHV/FCV

First vaccine First vaccine 8 - 10 weeks 8 - 10 weeks Second vaccineSecond vaccine 12 - 14 weeks12 - 14 weeks First booster vaccineFirst booster vaccine 1 year later 1 year later Booster vaccines Booster vaccines every 3 yearsevery 3 years

2006 AAFP Vaccine Advisory Panel Report- Feline Panleukopenia -2006 AAFP Vaccine Advisory Panel Report- Feline Panleukopenia -

Initial series of vaccinations

– 6-16 weeks of age

– 2+ doses 3-4 weeks apart Revaccinate one year later – single dose Then revaccinate no more frequently than every 3 yrs. Serious adverse reactions to FPV vaccines are rare CPV-2 can infect cats - FPV vaccines protect

JAVMA 229(9):1405-1441, 2006

FP MLV Vaccine-Induced StillbirthsFP MLV Vaccine-Induced Stillbirths

FPV Maternal Antibody in KittensFPV Maternal Antibody in Kittens

LONG-TERM IMMUNITY IN LONG-TERM IMMUNITY IN CATS VACCINATED WITH CATS VACCINATED WITH

AN INACTIVATED AN INACTIVATED TRIVALENT VACCINETRIVALENT VACCINE

Fred W. Scott, DVM, PhDFred W. Scott, DVM, PhD

Cordell M. Geissinger, BSCordell M. Geissinger, BS

Cornell Feline Health CenterCornell Feline Health Center

Feline Practice 25(4):12-19 (1997)Feline Practice 25(4):12-19 (1997)

AJVR AJVR 6060:652-658 (1999):652-658 (1999)

Duration of Immunity StudyDuration of Immunity StudyInactivated FHV-FCV-FPV VaccineInactivated FHV-FCV-FPV Vaccine

15 SPF kittens 15 SPF kittens Vaccinated 2x @ 8 & 11 wks of ageVaccinated 2x @ 8 & 11 wks of age No booster vaccines givenNo booster vaccines given

Placed in SPF breeding colonyPlaced in SPF breeding colony Offspring added to increase colony Offspring added to increase colony

No vaccine given to new catsNo vaccine given to new cats Original cats bled for serum on entryOriginal cats bled for serum on entry All cats bled at 3 years, then yearlyAll cats bled at 3 years, then yearly VN titers of serum run - FHV, FCV, FPVVN titers of serum run - FHV, FCV, FPV

The CatsThe Cats- After 7.5 Years -- After 7.5 Years -

9 vaccinates remained in colony9 vaccinates remained in colony– raised multiple littersraised multiple litters

8 unvaccinated contact controls 8 unvaccinated contact controls – raised multiple littersraised multiple litters

Mean VN Titer

FPV (Y1) FCV (Y2)

FHV (Y2)

Year after Vaccination1/6 3 4 5 6 7

01000200030004000500060007000

020406080100120140160

Scott & Geissinger, AJVR, 60:652-8 (1999)

Relative Efficacy of an Relative Efficacy of an Inactivated Triple VaccineInactivated Triple Vaccine7.5 Years after Vaccination7.5 Years after Vaccination

Feline parvovirusFeline parvovirus 100%100% Feline herpesvirusFeline herpesvirus 52% 52% Feline calicivirusFeline calicivirus 63% 63%

Duration of Immunity StudyDuration of Immunity StudyFPV ConclusionsFPV Conclusions

2 doses of inactivated, adjuvanted FPV 2 doses of inactivated, adjuvanted FPV vaccine provide solid immunity for at vaccine provide solid immunity for at least 7 yearsleast 7 years

1 cat still had solid protective Ab titer 14 1 cat still had solid protective Ab titer 14 years after vaccinationyears after vaccination

FPV - FPV - Disinfectants/Antiseptics Disinfectants/Antiseptics

Alcohols - ethyl, 70% isopropyl Phenolics - hexachlorophene, lysol Surfaces-active compounds - Quats,

amphoterics Biquanides - chlorhexidine Halogens - chlorine (hypochlorite), iodines Aldehydes - formaldehyde, glutaraldehyde Ethylene oxide

Inactivate FPVInactivate FPV

Not Inactivate Not Inactivate FPVFPV

Panleukopenia ~ Panleukopenia ~ ManagementManagement

Very important in shelters & pet storesVery important in shelters & pet stores Vaccinate newly arrived cats immediatelyVaccinate newly arrived cats immediately– MLV vaccineMLV vaccine

Place newly vaccinated cats in isolated, Place newly vaccinated cats in isolated, disinfected cages away from other catsdisinfected cages away from other cats

Use proper disinfectantsUse proper disinfectants– Household bleach (Clorox) 1:32Household bleach (Clorox) 1:32

– Cages, food and water dishes, floors, beddingCages, food and water dishes, floors, bedding

Prevent spread of virus by personnelPrevent spread of virus by personnel– Hands and clothingHands and clothing

– shoesshoes

BuddiesBuddies