disease virbagen...heart f ail u re ± liver disease ± bacterial perito n itis, ple u risy ±...

7
133 is feline coronavirus, there is the potential for the development of FIP . Following recommendations of the Coronavirus Study Group, in this chapter the virus will be called FCoV and the disease FIP . Any age of cat can develop FIP , but fifty percent of cats with FIP are younger than 2 years old. FIP typically occurs some weeks to months after a stress in the cat's life and can appear as effusive (or ‘wet’) or non-effusive (or ‘dry’). In the former, fluid collects in the abdomen and/or thorax, in the latter there is no fluid, but the cat loses weight, is anorexic, pyrexic, lymphopenic and shows clinical signs according to which organs are affected, the eyes, liver and brain being most commonly affected. Cats from multicat environments, for example pedigree and rescue cats, are most at risk of developing FIP for several reasons: - increased chance of becoming infected with feline coronavirus - increased dose of FCoV - increased stress (cats are naturally solitary animals) - increased probability of concurrent disease, lowering immune function Aetiology Family: Coronaviridae Genus: Nidovirales Feline coronavirus (FCoV) RNA enveloped virus Fragile virus, but resistant in environment for 3 to 7 weeks when protected by protein (faecal material) Susceptible to sodium hypochlorite (common household bleach) (Photo 1) Electron micrograph of feline coronavirus showing (arrow) the spikes or ‘corona’ from which it derives its name. Transmission The majority of cats infected with FCoV do not develop FIP , but become infected, shed virus in their faeces from 2-3 days post-infection, seroconvert at 18-21 days, stop shedding virus after 2-3 months to 7 months, then lose their antibodies. 13% of infected cats become lifelong carriers, continually shedding FCoV in their faeces and maintaining a high antibody titre. Feline Infectious Peritonitis Introduction Feline Infectious Peritonitis (FIP) is believed to be the leading infectious cause of cat mortality. FIP is an unusual consequence of infection with Feline Coronavirus (FCoV) – the majority of cats who encounter this virus are asymptomatic. The reason why some cats develop FIP is not fully understood. Soon after the discovery of FIP in 1963, it was recognised that many more cats were infected with FCoV than developed FIP and the hypothesis that there were two coronaviruses of the cat was offered.The hypothesis was that there is an avirulent, or enteric feline coronavirus (FECV) which differs from a virulent feline infectious peritonitis virus (FIPV). However, it is now recognised that wherever there 132 Feline Infectious Perotinitis Disease Disease Diane D. Addie - PhD, BVMS, MRCVS Honorary Senior Research Fellow, University of Glasgow, UK e-mail: [email protected] website: www.catvirus.com © Diane-D. Addie

Upload: others

Post on 16-Feb-2021

0 views

Category:

Documents


0 download

TRANSCRIPT

  • 133

    is feline coronavirus, there is the potential for the development of FIP. Followingrecommendations of the Coronavirus Study Group, in this chapter the virus will be calledFCoV and the disease FIP.

    Any age of cat can develop FIP, but fifty percent of cats with FIP are younger than 2 yearsold. FIP typically occurs some weeks to months after a stress in the cat's life and can appearas effusive (or ‘wet’) or non-effusive (or ‘dry’). In the former, fluid collects in the abdomenand/or thorax, in the latter there is no fluid, but the cat loses weight, is anorexic, pyrexic,lymphopenic and shows clinical signs according to which organs are affected, the eyes, liverand brain being most commonly affected.

    Cats from multicat environments, for example pedigree and rescue cats, are most at risk ofdeveloping FIP for several reasons:- increased chance of becoming infected with feline coronavirus - increased dose of FCoV- increased stress (cats are naturally solitary animals)- increased probability of concurrent disease, lowering immune function

    Aetiology

    Family: CoronaviridaeGenus: NidoviralesFeline coronavirus (FCoV)RNA enveloped virusFragile virus, but resistant in environment for 3 to 7 weeks whenprotected by protein (faecal material)Susceptible to sodium hypochlorite (common household bleach)

    (Photo 1) Electron micrograph of feline coronavirus showing (arrow) the spikes or ‘corona’ from which itderives its name.

    Transmission

    The majority of cats infected with FCoV do not develop FIP, but become infected, shedvirus in their faeces from 2-3 days post-infection, seroconvert at 18-21 days, stopshedding virus after 2-3 months to 7 months, then lose their antibodies. 13% of infectedcats become lifelong carriers, continually shedding FCoV in their faeces and maintaininga high antibody titre.

    Feline Infectious Peritonitis

    Introduction

    Feline Infectious Peritonitis (FIP) is believed to be the leading infectious cause of catmortality. FIP is an unusual consequence of infection with Feline Coronavirus (FCoV) – themajority of cats who encounter this virus are asymptomatic.The reason why some catsdevelop FIP is not fully understood. Soon after the discovery of FIP in 1963, it wasrecognised that many more cats were infected with FCoV than developed FIP and thehypothesis that there were two coronaviruses of the cat was offered.The hypothesis wasthat there is an avirulent, or enteric feline coronavirus (FECV) which differs from a virulentfeline infectious peritonitis virus (FIPV). However, it is now recognised that wherever there

    132

    Feline Infectious Perotinitis ‚ Disease

    Disease

    Diane D.Addie - PhD, BVMS, MRCVSHonorary Senior Research Fellow, University of Glasgow, UKe-mail: [email protected]: www.catvirus.com

    © D

    iane

    -D.A

    ddie

  • FIPdiagnosis

    Effusions - positive FCoV RT-PCRindicates a likely diagnosis of FIP

    Effusions - negative FCoV RT-PCRdoes not completely rule out adiagnosis of FIP

    Fine needle aspirate of an organ -positive FCoV RT-PCR indicates adiagnosis of FIP

    Fine needle aspirate of an organ -negative FCoV RT-PCR does notcompletely rule out a diagnosis ofFIP

    Positive result Negative result

    FCoVcontrol

    – faecalsample

    Only indicates viral shedding onday of sampling, repeat samplesover several months are requiredto determine that a cat is apersistent shedder.

    Only indicates that the cat wasnot shedding virus on the day ofsampling: repeat samples overseveral months are required todetermine that a cat is uninfected.

    Transmission is mainly indirect - not transplacental, and rarely direct.Virus is shed in thefaeces continuously (sometimes intermittently towards the end of infection).Virus is onlyfound in saliva very early in infection and then just for a matter of hours to 1-2 days (Addieand Jarrett, 2001).

    Viral Excretion of FCoV

    4 Viral excretion begins from 2 days post-infection in faeces (Pedersen et al., 2004)4 Only found in saliva in very early infection (first days) (Addie and Jarrett, 2001)4 Transient shedders (usually < 3 months) (Addie and Jarrett, 2001)4 Intermittent shedders (Addie and Jarrett, 2001)4 Carriers cats (for their lifespan) (Addie and Jarrett, 2001)4 Resistant cats (3%) (Addie and Jarrett, 2001)

    135

    Detection of virus has become more accessible in recent years using Polymerase ChainReaction (PCR). Because FCoV is an RNA virus, a DNA copy of the genome has to firstbe made using the enzyme reverse transcriptase (RT), thus FCoV detection is by RT-PCR.As with any test, not all tests are equal, and as with other tests, one should try to access alaboratory whose tests regularly feature in refered scientific and veterinary papers. Usesof RT-PCR are shown in table 1.

    PathogenesisFIP is a vasculitis

    The exact pathogenesis of FIP is not fully understood. We know that FCoV-infectedmonocytes adhere to endothelial cells, extravasate and differentiate into macrophages,setting up an inflammatory phlebitis and perivasculitis (Kipar et al, 2005) (photo 2). Theclinical signs are a consequence of the vascular damage – extensive vascular damage andleaking of plasma results in effusions in the body cavities. The earliest FIP occurs is around28 days post-infection and there is usually a history of stress, such as having been rehomed,or neutered. Effusive, or wet FIP is the acute form, occurring 4-6 weeks post-stress, andnon-effusive, or dry FIP is the chronic form and can occur months to years after infection.In effusive FIP many blood vessels are damaged, in non-effusive FIP, the immune responsehas been partly successful, walling off the infected vessels with pyogranulomata which canbecome quite large (in abdominal palpation and gross post mortem they can be mistakenfor tumours).

    Why one cat will go down with FIP,while its household companions, infected with the samevirus, remain perfectly healthy, is a matter for speculation. One theory is that a mutation(more accurately a deletion, Vennema et al, 1998) occurs in otherwise harmless FCoVs(sometimes called ‘feline enteric coronavirus’) which changes viral tropism fromenterocytes to macrophages. However, replicating FCoV has also been found in themacrophages of healthy cats (Simons et al, 2005).

    134

    Feline Infectious Perotinitis ‚ Disease

    Virus-contaminated surfaces:- litter trays

    - microscopic faecal particles

    Indirect horizontal transmission(faeces, infected fomites)

    INFECTED cat HEALTHY cat

    (Photo 2)FIP pyogranulomashowing a bloodvessel (BV) in thekidney surroundedby an infiltrate ofneutrophils andmacrophages.©

    Dia

    ne-D

    .Add

    ie

    BV

    Table 1:

  • 137

    Clinical Signs and Diagnostic Approach to FIP

    See algorithm - diagnostic approach to FIP (on page beside).There is no single diagnostic test for FIP, diagnosis can only be confirmed byhistopathology.

    FIP is one of the most difficult diseases to diagnose in the living animal, because it can presentwith almost any clinical signs.The clinical signs in FIP reflect the vascular damage which hasoccurred. In effusive FIP, damage to many blood vessels leads to leakage of essentially plasmainto the abdominal or thoracic cavities (or both). Presenting signs are therefore abdominaldistension or dyspnoea.The effusion is a modified transudate, has the same consistency asplasma and clots on exposure to air, the amount varies from a few mls to several hundredmls in the worst cases (photos 3 & 4). A thorough analysis of the effusion can lead to apresumptive diagnosis of FIP (see algorithm).The fluid should have > 35 g/l total protein,with an albumin:globulin ratio of less than 0.8.There should be few nucleated cells (less than2 x 109/l) and they should be mainly neutrophils and macrophages, not lymphocytes.Theeffusion should be sterile.One major differential diagnosis is bacterial peritonitis and pleurisy,where there are vast numbers of white blood cells in the effusion and bacteria present.Alpha 1 acid glycoprotein (AGP) is a useful adjunct to diagnosis, being extremely raised inFIP (> 1500 µl/ml) but normal in cardiomyopathy or tumour,which are the major differentialdiagnoses. However, AGP does also rise after trauma/surgery and with bacterial infections.FCoV serology is useful, since most cats with FIP have a very high antibody titre (thoughoccasionally cats with effusive FIP have a low antibody titre due to antibody being attachedto the vast amount of virus present, and therefore unavailable for the coronavirus antibodytest). Detection of replicating virus in the effusion by RT-PCR is indicative of FIP, as isdetection of FCoV in macrophages by immunofluorescence. In theory, effusion from a non-FIP FCoV-infected cat, suffering from some other condition, could co-incidentally have viruswhich had leaked into it from the blood, however, in practice, if FCoV is found in an effusion,the chances are very high that the cat is suffering from FIP. The same cannot be said foreither blood or faeces – a positive RT-PCR reaction on either of those is not diagnostic ofFIP, many healthy cats and cats with diseases other than FIP will give positive results.

    136

    Feline Infectious Perotinitis ‚ Disease

    (Photo 3)Effusive FIP showing

    clear fluid in thethoracic cavity and

    fibrin covering pleuraand pericardium. ©

    Dia

    ne-D

    .Add

    ie? U

    LTR

    ASO

    UN

    D/E

    XP

    LO

    RA

    TO

    RY

    LA

    PAR

    OT

    OM

    Y/B

    IOP

    SY/M

    RI

    Search for:± Tum

    or± H

    eart failure ± Liver disease± Bacterial peritonitis, pleurisy± D

    iaphragmatic hernia

    AN

    ALY

    SE

    EF

    FU

    SIO

    NU

    sually straw coloured, clear &

    not odiferousN

    OT

    FIP < 30g/litre Protein levels >35g/litre

    NO

    T FIP > 0.8 A

    lbumin: globulin ratio 1500 m

    g/ml

    Virus detection in m

    acrophages (IF) positive – IS FIPV

    irus detected by RT-P

    CR

    in the effusion – IS FIP

    Diagnostic A

    pproach to FIP

    CL

    INIC

    AL

    EX

    AM

    INA

    TIO

    Neffusive or non-effusive FIP?

    ? SP

    EC

    IAL

    ISE

    D L

    AB

    OR

    AT

    ORY

    TE

    ST

    ING

    High FC

    oV antibody titre in C

    SFN

    egative* FCoV

    RT-PCR

    on CSF Positive

    Negative FC

    oV RT-PC

    R on lym

    ph node FNA

    Positive

    Treat fo

    r F

    IP

    So

    me criteria m

    atch

    ? IF EFFU

    SION

    DIFFE

    RE

    NT

    FRO

    M FIP

    EFFU

    SION

    :± Bacteria found on cytology± C

    ells predominantly lym

    phocytes± C

    ancerous cells± Proteins < 30 g/L± A

    lbumin: globulin >0.8

    ± White blood cells >2 x 10

    9/l

    Often young cats (< 2 years old)

    ✔ H

    istory of multicat environm

    ent (e.g. rescue shelter, cat breeder)✔

    History of stress: adoption, boarding cattery, neutering± Pedigree (especially Persian)

    ME

    DIC

    AL

    H

    IST

    ORY

    All criteria m

    atch

    * Could still be FIP

    ??

    ?

    NO

    N E

    FF

    US

    IVE

    FIP

    ✔ Persistant m

    oderate pyrexia > 4 days✔

    Weight loss

    ✔ D

    ull✔

    Anorexia

    ✔ Enlarged m

    esenteric lymph node(s)

    ± Icterus✔

    Intraocular signs (uveitis, keratic precipitates, aqueous fl are, retinal vessel cuffi ng)

    ± Neurological signs (fi ts, ataxia, nystagm

    us)

    ? EF

    FU

    SIV

    E F

    IP✔

    Cat bright or dull

    ✔ M

    oderate pyrexia: 39.0 - 39.5oC

    ± Abdom

    inal distension/ascites± D

    yspnoea/pleural effusion± Pericardial effusion

    ? ?

    BL

    OO

    D S

    AM

    PL

    E✔

    Non-regenerative anem

    ia (haematocrit 1500 m

    g/ml)

    ✔ H

    yperbilirubinemia

  • 139138

    Haematology reveals lymphopenia (Paltrinieri et al., 2001) and a non-regenerative anaemia(haematocrit usually less than 30%). Biochemistry shows hypergammaglobulinaemia(polyclonal) and either normal or slightly low albumin levels, giving a low albumin:globulinratio. Albumin:globulin ratio was more useful in diagnosis than either total protein orgammaglobulin measurements (Hartmann et al, 2003).An A:G ratio over 0.8 rules out FIPwhereas less than 0.4 strongly suggests FIP. Between 0.4 and 0.8 other parameters need tobe considered. Bilirubin is often raised.AGP levels are greater than normal, but not as highas in effusive FIP (Addie, unpublished data). FCoV antibody titres are usually very high.

    The course of non-effusive FIP is chronic, with the cats frequently surviving weeks tomonths on treatment. Neurological signs (nystagmus, ataxia, seizures, paralysis) can be dueto meningitis, pyogranulomata impinging on nerves, or hydrocephalus. Once neurologicalsigns begin then death rapidly ensues.

    FIP Treatment

    Until the recent introduction of recombinant feline omega interferon (rFeIFN-ω) FIP wasdeemed incurable and a diagnosis of FIP was usually followed by euthanasia of the cat. Inthe first published report of rFeIFN-ω and prednisolone treatment of FIP, 4 cats of 12completely recovered and 2 survived 4 and 5 months (Ishida et al, 2004). Although effusiveand non-effusive FIP are not distinct diseases, but rather are gradations of the same process,at time of writing we have two protocols for FIP treatment (see table 2).

    Interferon omega is a monomeric glycoprotein related to interferon alpha and beta (butnot gamma). It is secreted by virus-infected leucocytes and has antiviral and anti-inflammatory properties. IFN omega stimulates natural killer cell activity and enhancesexpression of MHC class I but not class II antigens. It is not cross-reactive with IFN-alpha,so cats which have been treated with, and have made antibodies against IFN alpha will notneutralise IFN omega. IFN omega is acid resistant, so can be given orally. As with anyinterferon, it is most effective at the site of the infection.

    Before treating the cat, it is absolutely essential that every effort has been made to ensure acorrect diagnosis. Since FIP is an immune-mediated disease, treatment is directed atsuppressing the inappropriate immune response, usually using corticosteroids,which could bedisastrous in a lookalike condition of infectious aetiology (e.g. septic peritonitis or pleurisy).

    Bear in mind that, apart from corticosteroids, many of the drugs suggested in this chapterare not licensed for FIP treatment, so obtain written owner consent before embarking ontreatment with them.

    In the first days of treating humans with hepatitis C infection, only 6% of patients

    Feline Infectious Perotinitis ‚ Disease

    (Photo 4)Several hundred mls

    of ascites takenfrom the abdomen

    of a cat with effusiveFIP. Note the yellowtinge and the frothy

    appearance(because of highprotein content).

    Cats with effusive FIP are often bright and eating, though rapidly become dull and anorexic.Without effective treatment, death is usually within a few days.

    Major differential diagnoses for effusive FIP:4 tumour (adenocarcinoma, lymphoma)4 cardiomyopathy4 liver disease (tumour, cirrhosis, lymphocytic cholangitis)4 bacterial peritonitis or pleurisy4 pregnancy/obesity

    In non-effusive FIP, fewer, but larger, pyogranulomata form over longer periods of time andthe clinical signs are often directly attributable to the location of the lesions: for example,pyogranulomatas in the liver lead to icterus. Cats with non-effusive FIP are dull and typicallypresent with weight loss, anorexia, moderate pyrexia (103-104°F, 39.0 -39.5°C, which isunresponsive or recurrent), stary coat (photo 5).Most have intra-ocular signs, such as uveitis,aqueous flare, vitreous flare, keratic precipitates, or retinal vessel cuffing. Most cats with dryFIP have palpably enlarged mesenteric lymph nodes which are often mistaken for a tumour(Kipar et al., 1999).A positive FCoV RT-PCR result on a fine needle aspirate of an enlargedmesenteric lymph node is highly indicative of FIP and will often save the cat from having toundergo biopsy (Addie, manuscript in preparation).

    (Photo 5)An 8-month-old

    domestic shorthaircat with non-effusive

    FIP. Note that he isthin, his coat is stary,and his plantigradestance: he is ataxic. © D

    iane

    -D.A

    ddie

    © D

    iane

    -D.A

    ddie

  • 141140

    responded. Ten years later, with refinements to the protocol, over 60% of patients respond(Marian Horzinek, personal communication). At time of writing,we are still in the very earlydays of using interferon omega to treat FIP, hopefully as the protocols are modified, we shallsee a larger percentage of cases recover. Updates on FIP treatment are available on theinternet (www.catvirus.com).

    Possible modifications of the treatment protocol are offered here. Most have never beenused to treat FIP, or have only been used in a few cats.

    Thromboxane synthetase inhibitors (used in humans with asthma) cured one cat andgave remission for 8 months in a second effusive FIP (Watari et al., 1998).- dose: ozagrel hydrochloride 5-10 mg/kg bid and prednisolone at 2mg/kg/day

    Tepoxalin (Zubrin, Schering-Plough) is also a thromboxane synthetase inhibitor, its usein cats with FIP has never been evaluated.

    Dehydroepiandrosterone (DHEA) is a natural steroid hormone and precursor of thesexual hormones, 7-b-estradiol and 5-a-dihydrotestosterone. DHEA administration candownregulate endothelial adhesion molecules and reduce neutrophils extravasation(Barkhausen et al, 2006). It’s use in FIP would be to replace prednisolone in early effusiveFIP (may be less useful than prednisolone in non-effusive FIP). A synthetic derivative,16alpha-Bromo-epiandrosterone (epiBr) has been used without side effects in cats(Pedersen et al, 2003).- suggested dose: 40mg/cat/day

    TNF-alpha inhibitors – antibodies against TNF alpha (infliximab) – are used in humanswith rheumatoid arthritis and Crohns disease. TNF-alpha levels are also raised in FIP andcontribute to the inflammatory response. Chronic over-production of TNF-alpha resultsin cachexia, therefore it is likely that TNF-alpha inhibitors could be used to treat non-effusive, as well as effusive, FIP.- dose: unknown

    Cimetidine stimulates cell-mediated immunity (Lin et al, 2004). In FIP there is a shift fromcell-mediated (Th1) to humoral (Th2) immunity, there is also lymphopenia. Cimetidinecould possibly reverse these changes.- dose: 50 mg once a day

    Thalidomide has anti-inflammatory properties and pushes immune response from Th2to Th1. Non-toxic, but difficult to source.- dose: 50-100 mg once a day in the evening

    Salvianolic acid B is a matrix metalloproteinase 9 (MMP 9) inhibitor. Monocytes in FIPhave been shown to excrete MMP 9 (Kipar et al, 2005). Matrix metalloproteinases are

    Feline Infectious Perotinitis ‚ Disease

    Glucocorticoids:

    Dexamethasone 1 mg/kg intrathoracic orintraperitoneal injection once only,AND:

    Prednisolone sliding dose:

    4 mg/kg/day for 10-14 days reducing to 2 mg/kg/day for 10-14 days, then 1mg/kg/day for 10-14 days, then0.5 mg/kg/day for 10-14 days, then 0.25 mg/kg/day for 10-14 days, then0.25 mg/kg/e.o.d. …… and so on

    ceasing after complete remission ofclinical signs

    If, at any point, the cat’s conditionregresses, go back to the previous dose.

    Feline omega interferon:

    1MU/kg s/c e.o.d reducing to onceweekly if remission occurs

    Glucocorticoids:

    Prednisolone sliding dose:

    4 mg/kg/day for 10-14 days reducing to 2 mg/kg/day for 10-14 days, then 1mg/kg/day for 10-14 days, then0.5 mg/kg/day for 10-14 days, then 0.25 mg/kg/day for 10-14 days, then0.25 mg/kg/e.o.d. …… and so on

    ceasing after complete remission ofclinical signs

    If, at any point, the cat’s conditionregresses, go back to the previous dose.

    In addition, for FIP-related uveitis, topicalcorticosteroids will be used.

    Feline omega interferon:

    50,000 U per cat orally s.i.d untilglobulins, Hct, lymphocyte count andclinical signs return to normal.

    Diluting feline omega interferon(see diagram p.143):Feline omega interferon comes in vials of10 million units. It is reconstituted with 1mlof its diluent. 10 aliquots of 0.1 mL eachare prepared in insulin syringes (i.e. 1 MUper syringe). 9 syringes out of 10 are keptin the freezer (can be stored up to 6months).The 10th syringe is diluted with19.9 mL of sterile saline solution (NaCl0.9%) in order to obtain 20 mL ofsolution containing 1 MU of feline omegainterferon in total (50,000 U/ml).This 20mL are allocated into 20 syringes of 1mL.These syringes are stored in the fridgeat +4°C (not stable enough in the freezerbecause of dilution). Everyday, the cat isadministrated 1 mL of this diluted solution(containing 0.05 MU) by the oral route,using the syringe without the needle.

    Effusive FIP Non-effusive FIP

    Table 2.Treatment protocols for effusive and non-effusive FIP

  • 143

    Feline Infectious Perotinitis ‚ Disease

    zinc-dependent endopeptidases capable of breaking down extracellular matrix proteins,it is probably MMP 9 which is responsible for the leakiness of the blood vessels in effusiveFIP. MMP 9 inhibitors may be useful in early effusive FIP but are unlikely to be useful innon-effusive FIP.- suggested dose: 10 mg/kg once a day

    Tropisetron is a 5-hydroxytryptamine (3) receptor antagonist, bringing about areduction of TNF, IL-1 beta, IL-6 and prostaglandins (Muller et al, 2006).- suggested dose: 300 mg/kg once a day

    Anti-coronavirus drugs, not yet available commercially. The 3c-like protease of thecoronavirus has been well-characterised and prototype drugs have been developed foruse against human coronaviruses. It is likely that when these drugs become available thatthey could be useful in cats in the early stages of FIP.

    In addition, cats should be supported by good nutrition, fluids if dehydrated, and nursing.

    Monitoring Treatment

    Good indicators of treatment success or failure are globulin levels, albumin:globulin ratio,alpha 1 acid glycoprotein (AGP) levels, haematocrit and lymphocyte count. If thetreatment is working, globulin levels should return to normal, A:G ratio should increase,AGP levels fall to normal (500 µg/ml or less), haematocrit level should stay above 20% andlymphocyte count should return to normal. Measuring FCoV antibody titre is less useful inthe shorter term (weeks) since it will tend to remain high, but over a period of months, itsfall to zero indicates a full recovery and that it is safe to discontinue treatment. Weight gainis a useful indication of recovery in a non-effusive FIP case, but is less useful in effusive FIPbecause it may simply indicate that the amount of effusion has increased.

    Storage of Feline Omega Interferon:(See diagram page 143)

    Management of Multicat Houses

    Main source of infection: faeces

    The main mode of FCoV transmission is indirect - uninfected cats coming into contactwith the faeces of infected cats, usually by sharing a litter tray, and also by microscopic

    142

    Storage of Feline Omega Interferon:

    rFeIFN-ω diluent

    1

    2

    1 mL of 10 MU rFelFN-ω

    +

    4

    Rehydration ofrFeIFN-ω with its diluent

    1

    oraladministration

    6

    +19.9mLNaCI0.9 %

    Storage7

    Solution divided into10 syringes of 0.1 mL

    of 1 MU each

    2

    Syringes can bestored in the freezer up to6 months or in the fridge at

    +4°C up to 3 weeks

    3

    1 syringe is thawed anddiluted into 19.9 mL of sterile

    saline solution NaCl 0.9 %1/20 dilution

    4

    Solution divided into20 syringes of 1 ml of

    0.05 MU each

    5

    The solution forper os administration canbe stored in the fridge at

    +4°C for up to3 weeks

    7

    Storage 3

    5

    1 Oral administration of1 ml (0.05 MU) per day

    6

  • 145

    potentially high-risk environment, for example a rescue, boarding or breeding cattery,should receive this vaccine. Primucell will not prevent FIP in cats already viraemic withFCoV (Fehr et al, 1997).

    Selected references

    • Addie, D.D., and Jarrett, J.O. (2001) Use of a reverse-transcriptase polymerase chain reaction for monitoring felinecoronavirusshedding by healthy cats. Vet. Rec. 148, 649-653.

    • Addie D.D., Schaap I.A.T, Nicolson L., Jarrett O. (2003) Persistence and transmission of natural type I feline coronavirusinfection. J. Gen.Virol. 84 (10), 2735-2744.

    • Fehr D, Holznagel E, Bolla S, Hauser B., Herrewegh AAPM, Horzinek MC, Lutz H. 1997. Placebo-controlled evaluation of amodified life virus vaccine against feline infectious peritonitis: safety and efficacy under field conditions. Vaccine 15 10 1101-1109

    • Gonon V., Duquesne V, Klonjkowski B, Monteil M,Aubert A, Eloit M. (1999) Clearance of infection in cats naturally infectedwith feline coronaviruses is associated with an anti-S glycoprotein antibody response. J. Gen Virol. 80 2315-2317

    • Hartmann K, Binder C, Hirschberger J, Cole D, Reinacher M, Schroo S, Frost J, Egberink H, Lutz H, Hermanns W. (2003)Comparison of different tests to diagnose feline infectious peritonitis. J Vet Intern Med. 17(6): 781-790.

    • Ishida T., Shibanai A.,Tanaka S., Uchida K., Mochizuki M. (2004) Recombinant Feline Interferon Therapy of Feline InfectiousPeritonitis. J.F.M.S. 6, 107-109.

    • Kipar A., Koehler K., Bellmann S., Reinacher M. (1999) Feline infectious peritonitis presenting as a tumour in the abdominalcavity. Vet. Rec. 144, 118-122.

    • Kipar A , May H, Menger S,Weber M, Leukert W, Reinacher M. 2005 Morphologic features and development ofgranulomatous vasculitis in feline infectious peritonitis. Vet Pathol. 42(3):321-30.

    • Muller W, Fiebich B.L., Stratz T. 2006 New Treatment Options Using 5-HT(3) Receptor Antagonists in Rheumatic Diseases.Curr Top Med Chem.; 6(18):2035-2042.

    • Paltrinieri S., Grieco V., Comazzi S., Cammarata Parodi M. (2001) Laboratory profiles in cats with different pathological andimmunohistochemical findings due to feline infectious peritonitis (FIP). J. Feline Med. Surg. Sep. 3 (3), 149-59.

    • Pedersen N.C., North TW, Rigg R, Reading C, Higgins J, Leutenegger C, Henderson GL. (2003) 16alpha-Bromo-epiandrosterone therapy modulates experimental feline immunodeficiency virus viremia: initial enhancement leading to long-term suppression. Vet Immunol Immunopathol. 94(3-4):133-48.

    • Pedersen N.C., Sato R., Foley J.E., Poland A.M. (2004) Common virus infections in cats, before and after being placed inshelters, with emphasis on Feline Enteric Coronavirus. J.F.M.S. 6 83-88

    • Rohrer C, Suter PF, Lutz H. 1993. The diagnosis of feline infectious peritonitis (FIP): a retrospective and prospective study.Kleinterpraxis 38 6 379-389.

    • Shelly, S.M., Scarlett-Kranz J., Blue J.T. 1988 Protein electrophoresis on effusions from cats as a diagnostic test for felineinfectious peritonitis. JAAHA 24 495-500

    • Simons F.A.,Vennema H., Rofina J.E., Pol J.M., Horzinek M.C., Rottier P.J., Egberink H.F. (2005) A mRNA PCR for the diagnosisof feline infectious peritonitis. . 124(1-2):111-6.

    • Vennema H., Poland A., Foley J., Pedersen N.C. (1998) Feline infectious peritonitis viruses arise by mutation from endemicfeline enteric coronaviruses. Virology. 243 (1), 150-157.

    • Watari T., Kaneshima T.,Tsujimoto H., Ono K., Hasegawa A. (1998) Effect of thromboxane synthetase inhibitor on felineinfectious peritonitis in cats. J.Vet. Med. Sci. 60 (5), 657-659.

    Further reading FCoV/FIP WEBSITES:

    www.catvirus.com- FCoV/FIP website with the latest information for veterinary surgeons and information for cat owners and breeders.

    www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed- National Institutes of Health website with search facility for finding the latest scientific and veterinary publications on FCoV

    and FIP.

    www.felinecoronavirus.com- the website for FCoV/FIP symposia news.

    www.orionfoundation.com- a website for cat guardians, with a section for memorials for cats who have died of FIP which can be very useful as part of

    the grieving process for some owners.

    Feline Infectious Perotinitis ‚ Disease

    fomite transmission, for example on poop scoops.Thus good hygiene practices are thesingle best way of controlling FCoV infection.There should be adequate numbers of littertrays for the number of cats in a household: preferably one for each cat. Site litter traysaway from food areas. Covered or flushing litter trays are the best design to minimiseinfectious particles of litter being blown about and choose a non-tracking cat litter (such asWorld’s Best) and consider using specialised mats which further reduce cat litter tracking.Litter trays should be declumped at least once daily and cleaned and disinfected withhousehold bleach at least once a week.

    Prevent infection of uninfected cats by testing before introduction/mating

    Cats can be kept FCoV free only by preventing them coming into contact with faecalmatter from FCoV infected cats. Once a cat is FCoV antibody negative, any new cat shouldbe antibody tested BEFORE being introduced. FCoV antibody positive pedigree cats canstill be mated, but should only be mated with other FCoV seropositive cats and their kittensshould be early weaned and isolated to prevent them becoming infected (see below).A freeregister of FCoV tested cats is available on the internet on www.catvirus.com.

    FCoV-free households should introduce only FCoV seronegative cats. Seropositive catsshould be quarantined and retested every 3-4 months until they become seronegative. Forthese measures to be effective, it is essential that a reliable FCoV antibody test be used,and that the first dilution used by the laboratory is around 1:10, laboratories using a cutoffof 1:100 will miss some cats shedding FCoV. Detection of virus in faeces of healthy cats byRT-PCR may be used as an adjunct to FCoV serology (Addie and Jarrett, 2001).

    Maternally derived antibodies protect kittens until 5-6 weeks old

    Kittens of FCoV antibody positive cats are protected by maternally derived antibody untilthey are 5-6 weeks old. Pregnant FCoV antibody positive queens should be isolated 1-3weeks before kittening (3 weeks if they have concurrent feline herpesvirus infection).Thequeen and her kittens should be kept isolated from other cats in the house.At 5-6 weeks,the kittens should be removed to a clean room (free of cats for over a week,well vacuumed,and with a clean, disinfected litter tray). Kittens should be antibody tested when they are 10weeks of age or older and rehomed as soon as possible if seronegative. Antibody positivekittens can be retested every 4-6 weeks until they are seronegative, then homed.

    Vaccination of cats before first exposure to feline coronavirus

    There is only one vaccine against FIP available: Primucell (Pfizer). It is a temperature-sensitive mutant coronavirus which can only replicate in the cooler nares (and cannotreplicate systemically). It is administered intra-nasally, the first dose being given at 16 weeksof age, or later, and the second dose 3 weeks later. All FCoV-naïve cats going into

    144