FIP

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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.

Although all breeds can be infected, predisposition is seen with Devon rex, British and Abyssinian cats[2]. Although immunity to the FIP virus is extremely poor, not all cats experimentally exposed to FIPV develop FIP[3].

FIP is attributed to a triad of:

  1. exposure to the coronavirus
  2. genetic predisposition
  3. immunocompromisation[4]

The virus, normally present in the intestine, occasionally mutates and enters the circulation, resulting in generalised pyogranuloma throughout the body as a result of antigen-antibody complexes enhanced by neutrophil survival factors such as tumor necrosis factor and colony stimulating factor[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].

Cause

Approximately 1 in 200 cats are infected and develop FIP from exposure to coronavirus[8]. 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[9], 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[10].

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[11].

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[12].

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. In adult cats, infection of the brain 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 recognised 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

Diagnosis is based on presenting clinical signs in a young cat (usually under 3 years), together with ancillary diagnostic aids.

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[13].

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[14].

Treatment

No treatments have been shown to be effective at moderating the steady progression of this disease.

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[15]. 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[16].

Cyclosporin A has been shown to inhibit FIP viral replication in vitro, but has not been tested in vivo[17].

Glycyrrhizin (a licorice extract) has been reported as efficacious against coronaviruses but has not yet been tested in cats[18].

Eventually, cats with FIP 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. 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[19].

  • Controlling FIP in catteries

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

References

  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. Worthing KA et al (2012) Risk factors for feline infectious peritonitis in Australian cats. J Feline Med Surg 14(6):405-412
  3. 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 http://www.ncbi.nlm.nih.gov/pubmed/25265870
  4. O'Brien SJ et al (2012) Emerging viruses in the Felidae: shifting paradigms. Viruses 4(2):236-257
  5. 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
  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. 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
  9. 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
  10. Chang HW et al (2012) Spike protein fusion Peptide and feline coronavirus virulence. Emerg Infect Dis 18(7):1089-1095
  11. Pedersen, NC (2987) Virologic and immunologic aspects of feline infectious peritonitis virus infection. Adv Exp Med Biol 218:529-550
  12. 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
  13. 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
  14. Pedersen NC et al (1984) Pathogenic differences between various feline coronavirus isolates. Coronaviruses; molecular biology and pathogenesis. Adv Exp Med Biol 173:365-380
  15. Dr Jim Euclid, pers comm
  16. 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
  17. Tanaka Y et al (2012) Suppression of feline coronavirus replication in vitro by cyclosporin A. Vet Res 43(1):41
  18. De Clercq, E (2006) Potential antivirals and antiviral strategies against SARS coronavirus infections. Expert Rev Anti Infect Ther 4(2):291-302
  19. Addie, DD et al (2004) Feline luecocyte antigen class II polymorphism and susceptibility to feline infectious peritonitis. JFMS 6:59-62
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