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A 3-year-old Persian imported from the USA to Australia, which subsequently died of FIP one week after importation. Courtesy of Dr Jim Euclid
Microgranulomas on the surface of the liver and spleen in a 2-year-old British cat with FIP. Courtesy Dr Jim Euclid
Anterior uveitis secondary to FIP

FIP is an highly fatal inflammatory viral disease of domestic felidae worldwide (including large cats[1]), characterised by granulomatous vasculitis. The disease is associated with virulent forms of feline coronavirus (FCoV) infection.

Feline coronaviruses (FCoV) exist as two biotypes, feline enteric coronavirus and feline infectious peritonitis virus[2]. The latter (FIPV), which usually produces clinical signs of FIP, is not considered infectious to other cats due to the virus residing within enterocytes and macrophages outside the intestine.

Although all breeds can be infected, predisposition is seen with Devon rex, British and Abyssinian cats[3]. Although immunity to the FIP virus is extremely poor, not all cats experimentally exposed to FIPV develop FIP[4].

FIP is attributed to a triad of:

  1. exposure to the coronavirus
  2. genetic predisposition
  3. immunocompromisation[5]

Two forms have been identified in cats; the so called 'dry form' and 'wet form'. Clinical relevance of the two is less important in terms of prognosis. Once vasculitis occurs, the disease is invariably fatal[6].

Since the first description of feline infectious peritonitis (FIP) in 1963, the association between feline coronavirus (FCoV) and the development of high mortality systemic disease has been reported worldwide in all species of felids. It appears to have no breed or sex predilection, but the close proximity of many cats, such as occurs in multi-cat households, catteries and shelters increases the risk of disease[7].


The virus, normally present in the intestine, occasionally mutates and enters the circulation, resulting in generalised pyogranuloma. The method of entry of the FIP virus across the intestinal wall is via endocytosis into feline monocytes. The pathyway of internalization of the FIP virus is dependent upon a clathrin- and caveolae-independent pathway that strongly depends on dynamin and is slightly sensitive to cholesterol depletion. This uptake is strongly inhibited by the sterol-binding drugs nystatin and methyl-beta-cyclodextrin[8]. FECV can infect monocytes even in the absence of intestinal replication, suggesting that the gradual adaptation to these cells can allow non-enterotropic mutants to arise[9].

The FIP virus seems to avoid classical methods of viral isolation such as antigen-antibody binding and complement fixation through unknown means[10], although neutrophil survival factors such as tumor necrosis factor and colony stimulating factor may be involved[11].

Approximately 1 in 200 cats are infected and develop FIP from exposure to coronavirus[12]. In the United Kingdom approximately 40% of the domestic cat population is seropositive and where cats are housed together in multi-cat households, this figure increases still further to around 90%.

Natural infections with FCoV are usually transient, although a significant percentage of infections may be persistent. Most infections are asymptomatic or result in mild, self-limiting gastrointestinal disease. In a small percentage of animals (<5%), however, a fatal, multi-systemic, immune-mediated disease occurs. It was originally thought that there were two types of FCoV strains; feline infectious peritonitis virus (FIPV) and feline enteric coronavirus (FECV). It was originally thought that all strains cause systemic infection due to different virulence variants of FCoV[13], however recent studies have shown that spike proteins are unique in FIPV virus, suggesting that there are two different amino acids within 95% of FIPV infections which induce clinical disease in cats[14].

The virus is transmitted via oral, nasal and fecal secretions; prolonged contact with an infected cat is usually required for transmission. The incidence of FCoV infected cats in a closed population is typically found to be either zero or 80-90%, whereas in the free-roaming population, FCoV infections are around 25% of the population. The outcome of infection may not be known for months or years, as the virus may remain dormant. The outcome is influenced by the cat's immune response. Stress, vaccination and concurrent disease can exacerbated and trigger FIP. Antibodies against the FCoV virus may promote the disease rather than cause immunity[15].

There are four outcomes to feline coronavirus (FCoV) infection: the development of feline infectious peritonitis (FIP, which is immune-mediated), subclinical infection, development of healthy lifelong carriers and a small minority of cats who resist infection. Examination of the FCoV genome has shown that the same strain of virus can produce different clinical manifestations, suggesting that host genetic factors may also play a role in the outcome of infection. FIP is most prevalent amongst pedigree cats, although how much of this is due to them living in large groups (leading to higher virus challenge and stress which predisposes to FIP) and how much is due to genetic susceptibility is not known. If host genetics could be shown to play a role in disease, it may allow the detection of cats with a susceptibility to FIP and the development of increased population resistance through selective breeding. The feline leucocyte antigen (FLA) complex contains many genes that are central to the control of the immune response. Mutations in the 3c and 7b genes of feline coronavirus appear to be important in the spontaneous appearance of FIP in cats[16].

Burmese have been shown to have a predisposition to feline leukocyte antigen DRB-restricted polymorphism, suggesting a susceptibility to FIP in this breed.

Clinical signs

Symptoms of FIP can affect cats at any age.

In acute cases, fever is a common symptom, as well as lethargy and weight loss. Effusions within the abdominal and chest cavities may also rapidly develop, leading to peritonitis and pleuritis. Effusions may also within the vitreous humor of the eye and well as the brain.

In adult cats, meningitis can also cause neurological signs such as FIP-associated seizures, loss of balance, walking in circles and staggering. Many secondary problems, such as liver or kidney disease can occur with FIP. Any cat with fevers that do not respond to antibiotics should be considered as a candidate for this disease. In any chronic illness in cats for which no other cause can be found, FIP should be considered.

There are two commonly recognised syndromes associated with feline infectious peritonitis. In the 'wet FIP' cases, involving B-cell antibody-mediated immune response, fluid accumulates in the abdomen and it can become quite distended. This is known as the effusive form of FIP. The abdominal distension does not appear to be painful. The fluid that builds up in the wet form of FIP is called ascites when it occurs in the abdomen, and pleural effusion when it occurs in the thorax. The fluid is sticky and usually light yellow to golden colour, with a relatively large amount of protein.

The other recognized syndrome is the 'dry' form of FIP, a cell-mediated immune response resulting in granulomas, in which the symptoms of fever, weight loss and other clinical signs develop but there is no fluid accumulation. This is the more common form of the disease, especially in kittens.


Diagnosis is based on presenting clinical signs in a young cat (usually under 3 years), together with ancillary diagnostic aids. The three cardinal signs of 'wet' FIP are:

  • 1. persistent hyperthermia
  • 2. albumin/globulin ratio inversion
  • 3. presence of effusion (pleural, peritoneal, ocular)

A positive Rivalta test can be used but is not always accurate. In-house coronaviral antibody tests, although quick, are not necessarily accurate toward establishing active disease, and may only indicate prior exposure.

The standard method of testing for antibodies is a fluorescent antibody test. Up until the 1980s, most vets believed that any cat with antibodies to FIP should be euthanized to prevent the disease from spreading. We now know that the presence of FIP does not mean the virus is present. However, any antibody test that shows FIP titres >400 is suspicious, and a titre >800 is suggestive of active disease or a carrier state. Many cats with titres >1600 die from FIP within three months.

Although a strong suspicion of FIP can be determined based on clinical findings and ancillary blood tests, a definitive diagnosis requires immunofluorescent antibody testing of tissue samples take pre- or post-mortem[17]. The use of immunocytochemical (ICC) assay using body cavity effusion has been shown to be relatively unreliable as a diagnostic tool[18].

Common necropsy findings include icterus, abdominal or pleural effusion, and multifocal, pale pyogranulomatous lesions covering all affected surfaces. Histopathological examination of affected tissues often shows necrogranulomatous inflammation (large areas of necrosis with infiltration by macrophages and neutrophils). Vasculitis will be present, and appears as a vessel surrounded by an area of necrosis bordered by macrophages, lymphocytes, plasma cells, and neutrophils. Immunohistochemistry (IHC) for FCoV can be performed and aids in the definitive diagnosis of FIP[19].

The use of realt-time -PCR (RT-PCR) has shown sensitivity in a clinical setting with high sensitivity in cell-free body cavity effusion[20].


Treatment is usually symptomatic and supportive. In cats with pleural or peritoneal effusion, drainage may assist clinical symptoms in the short term. Broad-spectrum antibiotics, paticularly clindamycin, may be prudent.

The use of cortisone is debatable but has shown efficacy from anecdotal reports[21]. Prednisolone is the drug of choice, given at 10 mg orally once daily. Propentofylline, a phosphodiesterase inhibitor, has been recently tested in FIP-infected cats but has shown no significant improvement in mortality[22]. Cyclosporin A has been shown to inhibit FIP viral replication in vitro, but has not been tested in vivo[23].

In cases of mild 'dry form' (non-effusive FIP), some anecdotal evidence suggests the use of polyprenyl immunostimulant may prolong life in some cats[24].

Recent studies investigating the role of tumor necrosis factor (TNF) has led to the development of anti-TNF-α antibodies. In clinical studies (involving only 3 test cats with 3 controls), 2/3 cats responded to treatment while none of the controls did, suggesting this monoclonal antibody may have significant therapeutic benefit[25].

Eventually, cats with FIP usually succumb to overwhelming infections three to six months after a tentative diagnosis is made. Not all cats that are exposed to the FIP coronavirus will develop the disease.

Despite the paucity of adequate treatments available, recent use of a broad-spectrum coronavirus protease inhibitors (a 3CLpro inhibitor, GC376) has shown remarkable promise at reversing clinical signs in the wet form of FIP[26]. In cats experimentally infected with FIPV, antiviral treatment was started after the cats reached a clinical stage that would ultimately lead to death, if untreated. Cats were administered with 10 mg/kg protease inhibitor (GC376) by s.c. injection twice daily for 4 weeks. The antiviral treatment caused a rapid reversal of clinical signs and lymphopenia and reduction in viral titers in the macrophages from the ascites. Active infection was no longer apparent after 14–20 days of antiviral treatment and the treated cats remained normal under observation for as long as eight months. Further clinical trials are needed to assess this drugs applicability in a clinical setting.

Controlling FIP in catteries

In colonies of cats in which this disease is known to be present, estimates are that 8 to 20% of cats exposed to the virus will develop clinical signs of FIP. The rest of the cats may become immune to the disease or may simply not react to it. The reason that only a relatively small number of cats exposed to the virus develop the disease is unclear. Cats that do not have a strong immune system may be more susceptible to the disease. Many breeder cats are FIP positive yet never show disease. These cats are usually carriers of the disease, shedding the virus in their faeces and urine[27].

FIP virus itself lasts in the environment for up to 6 weeks. It is easily killed with disinfectants, so careful cleansing of a household may help prevent the spread of the disease if a cat with FIP is identified in a household with more than one cat. Due to the delay in the appearance of clinical symptoms once infection occurs, it is likely that most cats in a household have been exposed to the virus by the time it becomes evident that one of the cats is sick. Reducing stress levels by resisting overcrowding of cats in a household and providing adequate litter pans may be helpful in reducing the spread of FIP as well. Strict sanitation and isolation of infected cats and all susceptible kittens from each other is one approach. Vaccination is the other. Sanitation appears to be a major factor in preventing the spread of this virus. In catteries with known FIP exposure, it is possible to severely limit the spread of the disease by keeping kittens isolated from adult cats after the age of 6 weeks and following good sanitary practices. If kittens are not exposed to other cats in the household after six weeks of age, there is a very good chance that they can avoid infection. Once they go to a home where they are the only cat, there is little chance that they will be exposed to the virus. Because FIP is a disease of the immune system, it is also important to ensure the cats are fully vaccinated against cat flu and Chlamydia, and regular wormed and flea-treated, as any disease is likely to reduce a cat's health.

See also


  1. Stephenson N et al (2013) Feline infectious peritonitis in a mountain lion (Puma concolor), California, USA. J Wildl Dis 49(2):408-412
  2. Felten S et al (2016) Investigation into the utility of an immunocytochemical assay in body cavity effusions for diagnosis of feline infectious peritonitis. J Feline Med Surg. 2016 Feb 22. pii: 1098612X16630357.
  3. Worthing KA et al (2012) Risk factors for feline infectious peritonitis in Australian cats. J Feline Med Surg 14(6):405-412
  4. Pedersen NC et al (2014) The influence of age and genetics on natural resistance to experimentally induced feline infectious peritonitis. Vet Immunol Immunopathol Sep 16
  5. O'Brien SJ et al (2012) Emerging viruses in the Felidae: shifting paradigms. Viruses 4(2):236-257
  6. Brown MA (2011) Genetic determinants of pathogenesis by feline infectious peritonitis virus. Vet Immunol Immunopathol Jun 12
  7. Ward, J (1970) Morphogenesis of a virus in cats with experimental feline infectious peritonitis. Virol 41:191-194
  8. Van Hamme E et al (2008) Clathrin- and caveolae-independent entry of feline infectious peritonitis virus in monocytes depends on dynamin. J Gen Virol 89(9):2147-2156
  9. Desmarets LM et al (2016) Experimental feline enteric coronavirus infection reveals an aberrant infection pattern and shedding of mutants with impaired infectivity in enterocyte cultures. Sci Rep 6:20022. doi: 10.1038/srep20022
  10. Cornelissen E et al (2009) Absence of antibody-dependent, complement-mediated lysis of feline infectious peritonitis virus-infected cells. Virus Res 144(1-2):285-289
  11. Takano T et al (2009) Neutrophil survival factors (TNF-alpha, GM-CSF, and G-CSF) produced by macrophages in cats infected with feline infectious peritonitis virus contribute to the pathogenesis of granulomatous lesions. Arch Virol 154(5):775-781
  12. Rohrbach, BW et al (2001) Epidemiology of feline infectious peritonitis among cats examined at veterinary medical teaching hospitals. J Am Vet Med Assoc 218:1111
  13. Herrewegh, AA et al (1995) The molecular genetics of feline coronaviruses: comparative sequence analysis of the ORF7a/7b transcription unit of different biotypes. Virology 212:622
  14. Chang HW et al (2012) Spike protein fusion Peptide and feline coronavirus virulence. Emerg Infect Dis 18(7):1089-1095
  15. Pedersen, NC (2987) Virologic and immunologic aspects of feline infectious peritonitis virus infection. Adv Exp Med Biol 218:529-550
  16. Borschensky CM & Reinacher M (2014) Mutations in the 3c and 7b genes of feline coronavirus in spontaneously affected FIP cats. Res Vet Sci 30:S0034-5288(14)00218-00215
  17. DeGroot-Mijnes, JD et al (2005) Natural history of a recurrent feline coronavirus infection and the role of cellular immunity in survival and disease. J Virol 79: 1036-1044
  18. Felten S et al (2016) Investigation into the utility of an immunocytochemical assay in body cavity effusions for diagnosis of feline infectious peritonitis. J Feline Med Surg. 2016 Feb 22. pii: 1098612X16630357.
  19. Pedersen NC et al (1984) Pathogenic differences between various feline coronavirus isolates. Coronaviruses; molecular biology and pathogenesis. Adv Exp Med Biol 173:365-380
  20. Doenges SJ et al (2016) Comparison of real-time reverse transcriptase polymerase chain reaction of peripheral blood mononuclear cells, serum and cell-free body cavity effusion for the diagnosis of feline infectious peritonitis. J Feline Med Surg Jan 19. pii: 1098612X15625354
  21. Dr Jim Euclid, pers comm
  22. Fischer Y et al (2011) Randomized, placebo controlled study of the effect of propentofylline on survival time and quality of life of cats with feline infectious peritonitis. J Vet Intern Med 25(6):1270-1276
  23. Tanaka Y et al (2012) Suppression of feline coronavirus replication in vitro by cyclosporin A. Vet Res 43(1):41
  24. UC Davis
  25. Doki T et al (2016) Therapeutic effect of anti-feline TNF-alpha monoclonal antibody for feline infectious peritonitis. Res Vet Sci 104:17-23
  26. Kim Y et al (2016) Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor. PLoS Pathog 12(3):e1005531
  27. Addie, DD et al (2004) Feline luecocyte antigen class II polymorphism and susceptibility to feline infectious peritonitis. JFMS 6:59-62