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Feline infectious peritonitis

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Feline infectious peritonitis
FIP-infected kidney showing inflammatory response
SpecialtyInfectious diseases Edit this on Wikidata
SymptomsInitial phase: common cold-like symptoms.

Later on: ataxia, muscle weakness, dysphagia.

End phase: shortness of breath, urinary incontinence, paralysis.
Usual onsetCan take up to a year for symptoms to appear after exposure to virus
Duration1-month or less average life expectancy after diagnosis, especially in kittens
CausesMutation of feline coronavirus
TreatmentUK, Australia, Netherlands: GS-441524 (given orally as tablets) and its parent drug remdesivir (given by intravenous or subcutaneous injection)[1][2][3][4]
PrognosisUsually fatal without treatment, but with GS-441524 treatment over 80% of treated cats make a full recovery.
FrequencyCommon

Feline infectious peritonitis (FIP) is a common and aberrant immune response in cats to infection with feline coronavirus (FCoV).[5]

The virus and pathogenesis of FIP

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FCoV is a virus of the gastrointestinal tract. Most infections are either asymptomatic or cause diarrhea, especially in kittens, as maternally derived antibody wanes at between 5 and 7 weeks of age. The virus is a mutation of feline enteric coronavirus (FECV). From the gut, the virus very briefly undergoes a systemic phase,[6] before returning to the gut where it is shed in the feces.

The pathogenesis of FIP is complex. There is a general consensus that FIPVs arise from mutations enabling them to enter or replicate more successfully in monocytes (a type of white blood cell). However, many aspects of virus–host interactions affecting the disease remain uncertain, such as the factors that influence disease form (wet or dry), outcome (death or resistance), and host susceptibility.[7]

Virus and disease transmission

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There is a lack of evidence that FIP as such is transmissible from cat to cat, although it may explain rare mini-outbreaks of FIP.[8] However, the virus, FCov, is transmissible from cat to cat.

A study on 59 FIP infected cats found that, unlike FCoV, feces from FIP infected cats were not infectious to laboratory cats via oronasal route.[9] FCoV is common in places where large groups of cats are housed together indoors (such as breeding catteries, animal shelters, etc.). The virus is shed in feces, and cats become infected by ingesting or inhaling the virus, usually by sharing cat litter trays, or by the use of contaminated litter scoops or brushes transmitting infected microscopic cat litter particles to uninfected kittens and cats.[10] FCoV can also be transmitted through different bodily fluids. The virus is easily spread through direct contact between cats. The most common form of spreading is through saliva, as most multiple cat homes share food and water dishes.[11] Another major form of spreading is grooming or fighting. When an infected cat grooms a healthy cat, it leaves its contaminated saliva on the fur. Later, when the healthy cat goes to groom themselves, it ingests the contaminated saliva and then becomes infected.[12]

Clinical signs

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FIP effusive fluid

There are two main forms of FIP: effusive (wet) and non-effusive (dry). While both types are fatal, the effusive form is more common (60–70% of all cases) and progresses more rapidly than the non-effusive form.[citation needed]

Effusive (wet) FIP

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The hallmark clinical sign of effusive FIP is the accumulation of fluid within the abdomen or chest, which can cause breathing difficulties. Other symptoms include lack of appetite, fever, weight loss, jaundice, and diarrhea.[citation needed]

Non-effusive (dry) FIP

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Dry FIP will also present with lack of appetite, fever, jaundice, diarrhea, and weight loss, but there will not be an accumulation of fluid. Typically a cat with dry FIP will show ocular or neurological signs. For example, the cat may develop difficulty in standing up or walking, becoming functionally paralyzed over time. Loss of vision is another possible outcome of the disease.[citation needed]

Diagnosis

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Cytology of FIP-induced fluid showing neutrophils, macrophages and lymphocytes

Diagnosing effusive FIP

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Diagnosis of the effusive form of the disease has become more straightforward in recent years. Detection of viral RNA in a sample of the effusion (liquid drained from body), such as by reverse transcription polymerase chain reaction (RT-PCR) is diagnostic of effusive FIP.[13][14][15] However, that does require that a sample be sent to an external veterinary laboratory. Within the veterinary hospital there are a number of tests which can rule out a diagnosis of effusive FIP within minutes:

  1. Measure the total protein in the effusion: if it is less than 35 g/L, FIP is extremely unlikely.
  2. Measure the albumin to globulin ratio in the effusion: if it is over 0.8, FIP is ruled out; if it is less than 0.4, FIP is a possible—but not certain—diagnosis.[16]
  3. Examine the cells in the effusion: if they are predominantly lymphocytes (a type of white blood cell), then FIP is excluded as a diagnosis.

Diagnosing non-effusive FIP

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Non-effusive FIP is more difficult to diagnose than effusive FIP because the clinical signs tend to be more vague and varied: the list of differential diagnoses is therefore much longer. Non-effusive FIP diagnosis should be considered when the following criteria are met:[16]

  1. History: the cat is young (under 2 years old) and purebred: over 70% of cases of FIP are in pedigree kittens.[citation needed]
  2. History: the cat experienced stress such as recent neutering or vaccination[17]
  3. History: the cat had an opportunity to become infected with FCoV, such as originating in a breeding or rescue cattery, or the recent introduction of a purebred kitten or cat into the household.
  4. Clinical signs: the cat has become anorexic or is eating less than usual; has lost weight or failed to gain weight; has a fever of unknown origin; intra-ocular signs; jaundice.[18]
  5. Biochemistry: hypergammaglobulinaemia; raised bilirubin without liver enzymes being raised.
  6. Hematology: lymphopenia; non-regenerative—usually mild—anaemia.
  7. Serology: the cat has a high antibody titre to FCoV: this parameter should be used with caution, because of the high prevalence of FCoV in breeding and rescue catteries.

Non-effusive FIP can be ruled out as a diagnosis if the cat is seronegative, provided the antibody test has excellent sensitivity. In a study which compared various commercially available in-house FCoV antibody tests,[19] the FCoV Immunocomb (Biogal) was 100% sensitive; the Speed F-Corona rapid immunochromatographic (RIM) test (Virbac) was 92.4% sensitive and the FASTest feline infectious peritonitis (MegaCor Diagnostik) RIM test was 84.6% sensitive.

Treatment

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Eight-month-old kitten in end stage "dry" FIP, who had signs of anemia, lethargy, and weight loss. She exhibited eye changes (widening and paralysis of pupils) during seizures.

Because FIP is an immune-mediated disease, treatment falls into two categories: direct action against the virus itself and modulation of the immune response.

Antiviral drugs

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Antivirals (in the narrow sense) act by interfering with the enzymes or other biological processes in the FIP virus.

GS-441524 and remdesivir

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See also: GS-441524 and Remdesivir

An experimental drug called GS-441524 was used in a field experiment of 31 cats. After 25 days, five cats had died, eight had been cured and subsequently relapsed, and 18 had been cured without any subsequent relapses. The eight who relapsed were treated again, some with higher doses. Of these eight, one died and seven were cured, meaning that 25 of the 31 cats were ultimately cured of FIP. Although the drug is not yet (as of 2024) commercially available in the United States, the FDA allows its usage under certain conditions.[20] This study is considered very promising and may lead to commercially available medication for the treatment of FIP.[21]

In several countries oral GS-441524 tablets (and its injectable prodrug remdesivir) became legally available to vets for the treatment of FIP in cats, for example in Australia,[22] the Netherlands,[23][a] and the United Kingdom (since August 2021).[22] In naturally infected cats, a recovery rate of over 80% has been observed with GS-441524 treatment in several studies and in treatment programs in countries where the drug is legalised.[22][25][26][27]

GC376

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See also: GC376

An experimental antiviral drug called GC376 was used in a field trial of 20 cats: seven cats went into remission, and 13 cats responded initially but relapsed and were euthanized. This drug is not yet (as of 2017) commercially available.[28]

Molnupiravir

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See also: Molnupiravir

Facing a high-fatality FCoV-23 outbreak on the island nation of Cyprus, on 8 August 2023 the government released 80,000 anti-COVID molnupiravir pills from its national COVID-19 stockpile, in a bid to solve the feline coronavirus crisis in a more cost-effective manner.[29]

Immunostimulants

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Immunostimulants are drugs that make the immune system more active against the virus. The most common drugs of this class for treating FIP are either recombinant feline interferon omega (Virbagen Omega, Virbac) or human interferon alfa-2b. Since the human version ends up being targeted by the immune system for being a foreign antigen, the feline version feline interferon is more effective.[30]

An experimental polyprenyl immunostimulant (PI) is manufactured by Sass and Sass and tested by Dr. Al Legendre, who described survival over 1 year in three cats diagnosed with FIP and treated with the medicine.[31] In a subsequent field study of 60 cats with non-effusive FIP treated with PI, 52 cats (87%) died before 200 days, but eight cats survived over 200 days from the start of PI treatment for and four of those survived beyond 300 days.[32]

Anti-inflammatory drugs

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It is recommended to use an anti-inflammatory drug against FIP.[33]

Immunosuppressive drugs dampen the immune system, helping to reduce inflammation. The go-to immunosuppressive drug in FIP is prednisolone, a corticosteroid. There are no placebo-controlled trials showing prednisolone to be better than other anti-inflammatories.[33]

Prevention

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Vaccination

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There is no effective vaccine against FIPV. DNA vaccination with plasmids encoding FIPV proteins failed to produce immunity.[34] Rather, it was observed that antibodies to the FIPV spike protein exacerbate the disease.

In film

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A 2018 film titled Aeris, by Paul Castro Jr. and Aly Miller, and starring Frank Deal, Arabella Oz and Betsy Aidem, is about a kitten born with FIP that is purchased from a pet store and the owners' twelve days with it.[35][36] The film received an award at the 2018 Garden State Film Festival in the Narrative Short category[37] and was a Gold Kahuna winner at the 2018 Honolulu Film Awards.[38]

See also

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Explanatory notes

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  1. ^ At the moment, legal treatment with GS-441524 in the Netherlands is only available through vets from the Veterinary medicine department of Utrecht University. The drug is made in the University pharmacy. After a successful trial period starting in June 2023, the drug will become legally available for FIP treatment in cats to all vets in the country. Remdesivir can be legally used for treatment by all vets in the Netherlands under the cascade,[24] since its approval for the use in human COVID-19 treatment.

References

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  1. ^ Hartmann 2017. Coronavirus Infections (Canine and Feline), Including Feline Infectious Peritonitis. Chapter 224 p984-991. In Textbook of Internal Medicine, 4th Edition. Ettinger.
  2. ^ Kennedy and Little 2012. Infectious diseases, Chapter 33 p1038-1047. In The Cat. Clinical Medicine and Management, Little.
  3. ^ Pederson et al 2019. Efficacy and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis. J Feline Med Surg.21: 271–281
  4. ^ Dickinson et al 2020. Antiviral treatment using the adenosine nucleoside analogue GS‐441524 in cats with clinically diagnosed neurological feline infectious peritonitis J Vet Intern Med. 2020 Jul; 34(4): 1587–1593
  5. ^ Addie, D.; Belák, S.; Boucraut-Baralon, C.; Egberink, H.; Frymus, T.; Gruffydd-Jones, T.; Hartmann, K.; Hosie, M. J.; Lloret, A. (11 July 2009). "Feline infectious peritonitis. ABCD guidelines on prevention and management". Journal of Feline Medicine and Surgery. 11 (7): 594–604. doi:10.1016/j.jfms.2009.05.008. PMC 7129471. PMID 19481039.
  6. ^ Porter, E.; Tasker, S.; Day, M. J.; Harley, R.; Kipar, A.; Siddell, S. G.; Helps, C. R. (25 April 2014). "Amino acid changes in the spike protein of feline coronavirus correlate with systemic spread of virus from the intestine and not with feline infectious peritonitis". Veterinary Research. 45 (1). BiomedCentral: 49. doi:10.1186/1297-9716-45-49. PMC 4006447. PMID 24767677.
  7. ^ Pedersen, N. C. (August 2014). "An update on feline infectious peritonitis: Virology and immunopathogenesis". The Veterinary Journal. 201 (2): 123–132. doi:10.1016/j.tvjl.2014.04.017. PMC 7110662. PMID 24837550.
  8. ^ Pedersen, Niels C. (2014). "An update on feline infectious peritonitis: Virology and immunopathogenesis". The Veterinary Journal. 201 (2). Transmission of feline infectious peritonitis virus. doi:10.1016/j.tvjl.2014.04.017. PMC 7110662. PMID 24837550. S2CID 23453920.
  9. ^ Pedersen, Niels C.; Liu, Hongwei; Scarlett, Jennifer; Leutenegger, Christian M.; Golovko, Lyudmila; Kennedy, Heather; Kamal, Farina Mustaffa (2012). "Feline infectious peritonitis: Role of the feline coronavirus 3c gene in intestinal tropism and pathogenicity based upon isolates from resident and adopted shelter cats". Virus Research. 165 (1). 4.2. Role of the 3c gene of FECVs and FIPVs in intestinal tropism and fecal shedding. doi:10.1016/j.virusres.2011.12.020. PMC 7114484. PMID 22280883.
  10. ^ "How cats become infected with feline coronavirus: animation". 18 August 2011. Archived from the original on 21 December 2021 – via YouTube.
  11. ^ "Feline Infectious Peritonitis (FIP) Transmission - Feline Infectious Peritonitis (FIP)". HealthCommunities. Retrieved 2 November 2018.
  12. ^ "FIP". The Cat Community. Retrieved 2 November 2018.
  13. ^ Felten, S.; Leutenegger, C. M.; Balzer, H-J; Pantchev, N.; Matiasek, K.; Wess, G.; Egberink, H.; Hartmann, K. (2 August 2017). "Sensitivity and specificity of a real-time reverse transcriptase polymerase chain reaction detecting feline coronavirus mutations in effusion and serum/plasma of cats to diagnose feline infectious peritonitis". Veterinary Research. 13 (1). BiomedCentral: 228. doi:10.1186/s12917-017-1147-8. PMC 5541694. PMID 28768514.
  14. ^ Doenges, S. J.; Weber, K.; Dorsch, R.; Fux, R.; Hartmann, K. (1 April 2017). "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" (PDF). Journal of Feline Medicine and Surgery. 19 (4): 344–350. doi:10.1177/1098612X15625354. PMC 11119647. PMID 26787293. S2CID 7136727.
  15. ^ Longstaff, L.; Porter, E.; Crossley, V. J.; Hayhow, S. E.; Helps, C. R.; Tasker, S. (16 October 2015). "Feline coronavirus quantitative reverse transcriptase polymerase chain reaction on effusion samples in cats with and without feline infectious peritonitis". Journal of Feline Medicine and Surgery. 19 (2): 240–245. doi:10.1177/1098612X15606957. hdl:1983/2cba7130-9b6c-405f-9a47-276b7a09ed1d. PMC 10816577. PMID 26474594. S2CID 206692877.
  16. ^ a b "Dr. Addie - What is FIP?". CatVirus.com.
  17. ^ Riemer, F.; Kuehner, K. A.; Ritz, S.; Sauter-Louis, C.; Hartmann, K. (16 July 2015). "Clinical and laboratory features of cats with feline infectious peritonitis: A retrospective study of 231 confirmed cases (2000–2010)". Journal of Feline Medicine and Surgery. 18 (4): 348–356. doi:10.1177/1098612X15586209. PMC 11112253. PMID 26185109. S2CID 206692653.
  18. ^ Addie, Diane D. (19 April 2013). Feline Infectious Peritonitis and Coronavirus: Everything a cat lover needs to know. CreateSpace Independent Publishing Platform. ISBN 9781480208971.
  19. ^ Addie, D. D.; le Poder, S.; Burr, P.; Decaro, N.; Graham, E.; Hofmann-Lehmann, R.; Jarrett, O.; McDonald, M.; Meli, M. L. (1 February 2015). "Utility of feline coronavirus antibody tests". Journal of Feline Medicine and Surgery. 17 (2): 152–162. doi:10.1177/1098612X14538873. hdl:11586/146443. PMC 10816424. PMID 24966245. S2CID 21831168.
  20. ^ "FDA Announces Position on Use of Compounded GS-441524 to Treat FIP". FDA. 10 May 2024.
  21. ^ Pedersen, N. C.; Perron, M.; Bannasch, M.; Montgomery, E.; Murakami, E.; Liepnieks, M.; Liu, H. (13 February 2019). "Efficacy and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis". Journal of Feline Medicine and Surgery. 21 (4): 271–281. doi:10.1177/1098612X19825701. PMC 6435921. PMID 30755068.
  22. ^ a b c "Feline Infectious Peritonitis (FIP)". icatcare.org. International Cat Care. Retrieved 15 October 2023.
  23. ^ "Nu ook in Nederland behandeling voor katten met FIP". LICG.nl (in Dutch). Landelijk InformatieCentrum Gezelschapsdieren. Retrieved 15 October 2023.
  24. ^ "Cascade". cbg-meb.nl. Medicines Evaluation Board. 6 October 2018. Retrieved 15 October 2023.
  25. ^ "Successful Feline Infectious Peritonitis Treatment with Remdesivir at the RVC". RVC.ac.uk. Retrieved 15 October 2023.
  26. ^ "FIP Antivirals – Fight FIP". blogs.cornell.edu. Whittaker Lab - Cornell University. Retrieved 15 October 2023.
  27. ^ Jones, Sarah; Novicoff, Wendy; Nadeau, Julie; Evans, Samantha (30 July 2021). "Unlicensed GS-441524-Like Antiviral Therapy Can Be Effective for at-Home Treatment of Feline Infectious Peritonitis". Animals. 11 (8): 2257. doi:10.3390/ani11082257. ISSN 2076-2615. PMC 8388366. PMID 34438720.
  28. ^ Pedersen, N. C.; Kim, Y.; Liu, H.; Galasiti Kankanamalage, A. C.; Eckstrand, C.; Groutas, W. C.; Bannasch, M.; Meadows, J. M.; Chang, K. O. (13 September 2017). "Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis". Journal of Feline Medicine and Surgery. 20 (4): 378–392. doi:10.1177/1098612X17729626. PMC 5871025. PMID 28901812. S2CID 4595813.
  29. ^ Smith, Helena (10 August 2023). "Cyprus to begin treating island's sick cats with anti-Covid pills". The Guardian. Archived from the original on 13 August 2023. Retrieved 15 August 2023.
  30. ^ Forney, Barbara. "Interferon Alpha-2B for Veterinary Use". Wedgewood Pharmacy.
  31. ^ Legendre, A. M.; Bartges, J. W. (1 August 2009). "Effect of Polyprenyl Immunostimulant on the survival times of three cats with the dry form of feline infectious peritonitis". Journal of Feline Medicine and Surgery. 11 (8): 624–626. doi:10.1016/j.jfms.2008.12.002. PMC 7130077. PMID 19482534.
  32. ^ Legendre, A. M.; Kuritz, T.; Galyon, G.; Baylor, V. M.; Heidel, R. E. (14 February 2017). "Polyprenyl Immunostimulant Treatment of Cats with Presumptive Non-Effusive Feline Infectious Peritonitis In a Field Study". Frontiers in Veterinary Science. 4: 7. doi:10.3389/fvets.2017.00007. PMC 5306384. PMID 28261584. S2CID 4835088.
  33. ^ a b Hugo, T. B.; Heading, K. L. (January 2015). "Prolonged survival of a cat diagnosed with feline infectious peritonitis by immunohistochemistry". The Canadian Veterinary Journal. 56 (1): 53–8. PMC 4266056. PMID 25565715.
  34. ^ Glansbeek, H. L.; Haagmans, B. L.; Te Lintelo, E. G.; Egberink, H. F.; Duquesne, V.; Aubert, A.; Horzinek, M. C.; Rottier, P. J. M. (2002). "Adverse effects of feline IL-12 during DNA vaccination against feline infectious peritonitis virus". Journal of General Virology. 83 (Pt 1): 1–10. doi:10.1099/0022-1317-83-1-1. PMID 11752695.
  35. ^ "Aeris (2018)". Rotten Tomatoes.
  36. ^ "The Story of Aeris: A Legacy Inspired by Love". The Purrington Post. 30 November 2016.
  37. ^ "Garden State Film Festival 2018 Winners". New Jersey Stage. 10 April 2018.
  38. ^ "2018 Winners, 2018 Gold Kahuna Winners". Honolulu Film Awards.
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