Feline infectious peritonitis (PIF)

Definition:

This is a viral infectious disease of the cat and other wild Felidae caused by a mutated virus (coronavirus). Lesions are vasculitis with a pyogranulomatous infection. This is a special disease because it is on the border between a virus disorder and an autoimmune disorder.

There are various forms of the disease but two mean:

- Effusive form, the more characteristic: liquid collections (effusions) in the thorax and the abdomen.
- Noneffusive form: nonexsudative lesions, many organs or systems can be concerned (so, many symptoms are possible).

 

History:

This disease is known since 60's. Around 1970, a coronavirus disease is confirmed, and since that date, questions remain about this disorder in spite of the numerous studies.

 

Importance:

- Medical importance: diagnosis is very difficult to establish, especially in ante mortem and prognosis is always desperate (2 months without treatment, 6 months with treatment). Actually, there is no real well-fitted and effective treatment. And finally, prevention is very difficult to lead, especially in breedings.
- Legal importance because it is a crippling vice in France.
- For the multiple-cat households (because big population of cats increase circulation and mutation of the virus).

 

Etiology:

The responsive virus is a Coronaviridae: Feline Coronavirus (FCoV). There are 2 different pathotyps:

- FECV (Feline Enteritic CoronaVirus) which results in enteritic infection with mild gastrointestinal signs or even no sign at all.
- FICV (Feline Infectious CoronaVirus) which causes FIP with severe lesions of vascularitis.

To date there is no diagnostic method to differentiate these 2 pathotyps. There is no serologic difference between them.

 

Coronavirus has an important capacity to mute. First, cats should be infected by the FECV which is only responsive of enteritis because it only multiplies in enterocyts (intestine cells). After mutation(s) in the animal organism, FECV form should become FICV form. Pathogenic power (i.e. multiplication capacity in white blood cells, and thus invasion of the entire organism) should due to mutation. Today, there is no RT-PCR technique (Reverse transcriptase Polymerase Chain Reaction = RNA molecular analysis) available to differentiate the 2 virus forms, because mutations vary and are unpredictable from a cat to another one. So, Lots of FICV exist, each being appropriate to every animal. FICV form is not transmissible to another cat (ill cats don't excrete the virus) contrary to the FECV form, which is the contaminant agent and is excreted by carrier cats.

 

Epidemiology:

As it is impossible to differentiate the 2 types of virus, the global prevalence (=number of infected cats at a moment of their life) for the coronavirus does not correspond to prevalence of FIP. This global prevalence is 25-30% for a individual pet cat, and is 75-100% for a multiple-cat household. The more there are cats living together, the more the percentage is high.
The mortality is more representative of the real prevalence of FIP (because the disease leads to death). Among the seropositive cats (i.e. those that met the virus at one time of their life), there is 1/5000 dead cat (in the big affected breedings, mortality can increase to 10%). So, after a coronavirus contact with a cat, the risk to develop FIP is rare.

Coronavirus is shed continuously or intermittently in feces and rarely in saliva (maybe the urine?) of infected cats. It is very contagious. Excretion starts very early (sometimes 3 days after infection) and lasts more than 8 months after seroconversion and until 12 to 24 months.
Transmission can be:

- Direct: oro-nasal way (cat to cat)
- Indirect: soiled litter box, mess tin.
- (transplacental: but only in experimental conditions).

Several receptivity or predisposition factors exist, but the main factor is the age of cats. At the beginning of their life, kittens are protected by maternal antibodies until 6 weeks, and then they become receptive. Young cats aged 3 months to 3 years, but also less frequently old cats (10-14 years) are the most exposed and sensitive.

This disease is very important for multiple-cat households; this is a breeding problem because the FECV is very contagious. For example, if one infected cat is put with a non-infected multiple-cat household, 95 to 100% of the cats will be contaminated in 2 weeks!
In American and Australian studies, breed male cats were more susceptible to develop FIP because they come from breeding (colony) and because of genetically determined host factors (a polygenic inheritance is suspected in American Burmeses and Persians, and Australian British Shorthair, Devon Rex and Abyssinians lines).
Occasional contacts (feline exhibitions and outside coverings) were not considered as an important risk of infection.

 

Pathogeny:

Even if the virus mute and get its pathogenic power, cat can resist to it. So he will develop or not the disease, in one form or the other. All is depending on the host and his immune response (especially, the cell-mediated immunity). Stress (new home, new animal, new owner.) is known to be the acute form triggering factor.
After oro-nasal contamination, virus arrives in the small intestine (and less but also in the respiratory epithelium). In the case of mutation, the virus colonizes macrophages (mononucleated white cells) and disseminates throughout the mesenteric lymph nodes and the blood (=viremia) for about 1 week. Viral multiplication capacity in cells depends on its virulence. The global incubation is 7 to 16 days.

 

- If cell-mediated immunity is excellent, the cat recovers and doesn't develop FIP.
- If cell-mediated immunity is partial, a deferred form of FIP develops (latent form) and due to stress factors, the disease becomes fulminating.
- If cell-mediated immunity is insufficient, the non-effusive form develops.
- If cell-mediated immunity is zero, the effusive form develops.

 

Clinical features:

There are 3 mean forms:

- Effusive form (2/3 of the cases)
- Non-effusive form (1/3 of the cases)
- Ocular form, which is particular because the prognosis can reach 1 year without treatment.

The common and general signs are not specific: anorexia, weight loss, recurrent fever and general malaise, dull hair.

Effusive form:
It is characterized by a leakage of fluid in the organism's cavities: peritoneal cavity (peritonitis), pleural space (pleurisy), pericardial space (pericarditis), subcapsular space of the kidneys, genital serous membranes...
Functional signs can be dyspnoea (respiratory difficulties). 
Peritoneal fluid is one of the most characteristic signs, but the collection can stabilize at one level and even be of limited volume. It's due to vasculitis lesions (hypersensitivity type III phenomenon) and secondary inflammation.

Noneffusive form:
Less frequent, symptoms are various depending on affected organs.

- Nervous signs: convulsive seizure, loss one's balance, change of behaviour, tremors, weakness or paralysis.
- Hepatic disorders: big liver (felt by the veterinarian), icterus, vomiting, increased drinking, diarrhoea, pyogranulomatous hepatitis.
- Renal disorders: renal failure, pyogranulomatous nephritis.
- Digestive disorders: enteritis, abnormal intestinal loops on physical examination.

 

Ocular form:
One or both eye(s) can be affected : uveitis with hypopion or hyphema, detachment of the retina (amotio retinae), retinochoroïditis, retinal haemorrhage.

 

Diagnosis:

This is a challenge for the practitioner because the diagnosis is always very difficult to make. Symptoms are not specific: anorexia, weakness, fever, weight loss.

It is together with the laboratory analysis that strong presumptions will be made:

- Blood cells analysis: lymphocytes cells and red blood cells are often under the normal values (respectively lymphopenia, anemia). Less frequently, neutrophils are increased.
- Blood biochemistry test: total proteins in serum are increased (>80 g/L) : albumin (the mean protein in serum) is normal or slightly decreased whereas the gamma-globulins are increased. If the albumin/globulin ratio is >0.8, the cat don't have the FIP. For the moment, laboratories aren't able to dose the orosomucoïd protein which could be an interesting diagnosis tool. In general, during the last 2 weeks before death on an affected cat, bilirubin and AsAT increase.
- Collection fluids : lemon yellow, viscous, easy-coagulable (in cold water or in acid), nonsuppurative (without microorganism). Fluid density (>1.017) and protein count (>35 g/L) are very high. The albumin/globulin ratio is <0.4 and there is nearly no cell.
- Cerebrospinal fluid (CSF) in neuronal cases: rich in proteins, low cell count and sometimes anti-FCoV antibodies detection.
- Blood serology (=anti-FCoV antibodies dosage diagnosable since 7 to 10 days after infection): this test is the easier to perform but unfortunately, no distinction between the FECV and the FICV is possible. So, if serology is positive, the practitioner could only say that the cat has been contaminated by the coronavirus at one time, but he certainly not could say that the cat has FIP infection! Should the opposite occur, lots of non-affected cats should be condemned. "Coronavirus serology killed more cats than the FIP itself" (F. Scott).
- Fluid collection or CSF serology: if it is strongly positive, it is in favour of FIP but it's not completely sure. If it's negative, FIP can't be totally dismissed because the disease "consume" antibodies which can decrease to a low level.
- RT-PCR (Reversed Transcriptase - Polymerase Chain Reaction) or immunofluorescence (which are techniques of RNA (similar to DNA) detection): the problem is the same as above, there is no difference between FECV RNA and FICV RNA. But we'll suspect FIP if the test is widely positive on peritoneal fluid or CSF because only the FICV is able to go through the digestive barrier. Depending on the form of the disease, other fluids or tissues can be tested (renal or hepatic biopsies, aqueous humor, blood.).
- Legally, the pyogranulomatous and vasculitis lesions on histopathology after necropsy are of diagnosis consideration for the legislator.

Be careful, other diseases cause fluid collection in the cat like heart failure, lymphoma, cholangiohepatitis or septic peritonitis/pleurisy. So don't only focus on FIP when fluid collection occurs in the cat, but explore also the other causes.

 

Treatment:

Without treatment, survival rate is 8 days to 2 months, except in ocular form (1 year). With treatment, survival rate reaches 6 months. A Taiwanese study (2009) shows that some parameters (white blood cells, bilirubin, AsAT, potassium and sodium) allows assessment of survival rate of the cat with the help of a point scale (ex: survival rate of at least 2 weeks / less than 2 weeks / less than 3 days).
Few treatments are effective. Antibiotics and immunosuppressive antiinflammatory drugs have been used without result. Antiviral drugs (Ribavirin) or vitamins make poor results. Today, human recombinant interferon and feline recombinant interferon omega (VIRBAGEN omega®, Virbac) are hopefully. But this treatment is long, expensive and new (lack of room for effectiveness). The protocol is in two-stages : 1) fluid collection aspiration + in situ injection of dexamethasone, 2) interferon + prednisolone (doses and frequency of administration change depending on the cat clinical status).
Recently, a Japanese study showed that cyclosporin A (= immunosuppressive drug) inhibited FICV replication in vitro, but further studies are necessary to verify the practical value of cyclosporin A as an anti-FICV treatment in vivo (Suppression of feline coronavirus replication in vitro by cyclosporin A. Tanaka Y, Sato Y, Osawa S, Inoue M, Tanaka S, Sasaki T.Vet Res. 2012 Apr 30;43(1):41).

 

Prevention:

There is no vaccine in France. One intranasal vaccine (Primucell®, Pfizer) is used in Great-Britain and North of America. Its effectiveness is discussed.

Prevention is above all necessary for colonies (breeding catteries, humane rescue organizations, multiple-cat owners). The aim is to restrict coronavirus circulation within the multiple-cat household:

- Decrease the faecal contamination by cleaning the perianal area (especially with long hair cats) and management of the litter box: one litter box for one or two cats maximum, removing of stools every day, cleaning and disinfection of the litter box with bleach at least once a week (or every day in exposed multiple-cat households), cleaning daily around the litter boxes, mess tins kept remote of litter box area.
- Limit the number of cats in the breeding (8-10 maximum).
- Put in quarantine for 3 weeks the new cats entering in the breeding. Test twice the new cats after an interval of one month before introduce them with the rest of the breeding.

 

In the particular case of affected colonies, it is in more recommended to:

- Evaluate antibodies rate of each cat and group them together / isolate them according to their infection rate.
- Evaluate faecal excretion by quantitative PCR analysis of stools or rectal swab (about 1/3 seropositive cat is excretory). Chronic excretories are the most worrisome cats because they are asymptomatic carrier for all their life and they excrete important quantity of virus in their stools.
- After excretory confinement, analysis is repeated every month in order to verify if the excretion is chronic or transient.
- Wean quickly kittens (around 5-6 weeks) in order to separate them from the mother.
- Remove from reproduction animals which have a high serologic rate (i.e. the chronic carriers).
- Do not introduce the new kittens before 16 weeks of age or isolate them until this age in order to avoid contamination.

Coronavirus is long time resistant in the environment (7 weeks in desiccated secretions at 21°C). But it's quickly inactivated by usual detergents (only soap and water).

 

 

In conclusion:

To converse and to work with his veterinarian is essential for the breeder in order to manage his breeding.


Sources:
Chabanne L. Internal medicine lessons of the 3rd year at the National Veterinary School of Lyon, 2005.
Casseleux G & Isnar J. Diagnostic de la PIF et méthodes d'évaluation de la contamination d'un effectif par les coronavirus. Le nouveau praticien vétérinaire canine, féline, hors série - les maladies infectieuses. 2006. 111-116.
Worthing KA, Wigney DI, Dhand NK, Fawcett A, McDonagh P, Malik R, Norris JM. Risk factors for feline infectious peritonitis in Australian cats. J Feline Med Surg. 2012 Jun;14(6):405-12. Epub 2012 Mar 7.
Tsai HY, Chueh LL, Lin CN, Su BL. Clinicopathological findings and disease staging of feline infectious peritonitis: 51 cases from 2003 to 2009 in Taiwan. J Feline Med Surg. 2011 Feb;13(2):74-80. Epub 2011 Jan 8.