Feline Infectious Peritonitis
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Feline infectious peritonitis (FIP) is a common and aberrant immune response in
cat The cat (''Felis catus''), also referred to as the domestic cat or house cat, is a small domesticated carnivorous mammal. It is the only domesticated species of the family Felidae. Advances in archaeology and genetics have shown that the ...
s to infection with feline coronavirus (FCoV).


The virus and pathogenesis of FIP

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, before returning to the gut where it is shed in the feces. The
pathogenesis In pathology, pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes . Descript ...
of FIP is complex. There is a general consensus that FIPVs arise from mutations enabling them to enter or replicate more successfully in
monocyte Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and monocyte-derived dendritic cells. As a part of the vertebrate innate immune system monocytes also ...
s (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.


Virus and disease transmission

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. 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. FCoV is common in places where large groups of cats are housed together indoors (such as breeding catteries,
animal shelter An animal shelter or pound is a place where stray, lost, abandoned or surrendered animals – mostly dogs and cats – are housed. The word "pound" has its origins in the animal pounds of the agricultural communities, where stray livestock w ...
s, 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. 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. 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.


Clinical signs

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.


Effusive (wet) FIP

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 Jaundice, also known as icterus, is a yellowish or, less frequently, greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving ...
, and diarrhea.


Non-effusive (dry) FIP

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 An eye is a sensory organ that allows an organism to perceive visual information. It detects light and converts it into electro-chemical impulses in neurons (neurones). It is part of an organism's visual system. In higher organisms, the eye ...
or
neurological Neurology (from , "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the nervous system, which comprises the brain, the s ...
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.


Diagnosis


Diagnosing effusive FIP

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 Reverse transcription polymerase chain reaction (RT-PCR) is a laboratory technique combining reverse transcription of RNA into DNA (in this context called complementary DNA or cDNA) and amplification of specific DNA targets using polymerase cha ...
(RT-PCR) is diagnostic of effusive FIP. 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: # Measure the total protein in the effusion: if it is less than 35 g/L, FIP is extremely unlikely. # Measure the
albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All of the proteins of the albumin family are water- soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Alb ...
to
globulin The globulins are a family of globular proteins that have higher molecular weights than albumins and are insoluble in pure water but dissolve in dilute salt solutions. Some globulins are produced in the liver, while others are made by the immune ...
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. # Examine the cells in the effusion: if they are predominantly
lymphocytes A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include T cells (for cell-mediated and cytotoxic adaptive immunity), B cells (for humoral, antibody-driven adaptive immunity), and ...
(a type of white blood cell), then FIP is excluded as a diagnosis.


Diagnosing non-effusive FIP

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: # History: the cat is young (under 2 years old) and purebred: over 70% of cases of FIP are in pedigree kittens. # History: the cat experienced stress such as recent neutering or vaccination # 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. # Clinical signs: the cat has become
anorexic Anorexia nervosa (AN), often referred to simply as anorexia, is an eating disorder characterized by Calorie restriction, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. Individuals wit ...
or is eating less than usual; has lost weight or failed to gain weight; has a
fever of unknown origin Fever of unknown origin (FUO) refers to a condition in which the patient has an elevated temperature (fever) for which no cause can be found despite investigations by one or more qualified physicians. Mandell's Principles and Practices of Infection ...
; intra-ocular signs; jaundice. # Biochemistry: hypergammaglobulinaemia; raised
bilirubin Bilirubin (BR) (adopted from German, originally bili—bile—plus ruber—red—from Latin) is a red-orange compound that occurs in the normcomponent of the straw-yellow color in urine. Another breakdown product, stercobilin, causes the brown ...
without liver enzymes being raised. #
Hematology Hematology (American and British English spelling differences#ae and oe, spelled haematology in British English) is the branch of medicine concerned with the study of the cause, prognosis, treatment, and prevention of diseases related to bloo ...
:
lymphopenia Lymphocytopenia is the condition of having an abnormally low level of lymphocytes in the blood. Lymphocytes are a white blood cell with important functions in the immune system. It is also called lymphopenia. The opposite is lymphocytosis, which r ...
; non-regenerative—usually mild—
anaemia Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availab ...
. #
Serology Serology is the scientific study of Serum (blood), serum and other body fluids. In practice, the term usually refers to the medical diagnosis, diagnostic identification of Antibody, antibodies in the serum. Such antibodies are typically formed in r ...
: 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, 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

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

Antiviral Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Antiviral drugs are a class of antimicrobials ...
s (in the narrow sense) act by interfering with the enzymes or other biological processes in the FIP virus.


GS-441524 and remdesivir

An experimental drug called
GS-441524 GS-441524 is a nucleoside analogue antiviral drug which was developed by Gilead Sciences. It is the main plasma metabolite of the antiviral prodrug remdesivir, and has a half-life of around 24 hours in human patients. Remdesivir and GS-441524 w ...
was used in a
field experiment Field experiments are experiments carried out outside of laboratory settings. They randomly assign subjects (or other sampling units) to either treatment or control groups to test claims of causal relationships. Random assignment helps establ ...
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. This study is considered very promising. In 2024, GS-441524 became commercially available in the U.S. through at least one compounding pharmacy. Previously, the FDA allowed its usage under certain conditions. In several countries oral
GS-441524 GS-441524 is a nucleoside analogue antiviral drug which was developed by Gilead Sciences. It is the main plasma metabolite of the antiviral prodrug remdesivir, and has a half-life of around 24 hours in human patients. Remdesivir and GS-441524 w ...
tablets (and its injectable prodrug
remdesivir Remdesivir, sold under the brand name Veklury, Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. is a Broad-spectrum antiviral drug, broad-spectrum ...
) became legally available to vets for the treatment of FIP in cats, for example in Australia, the Netherlands, and the United Kingdom (since August 2021). 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.


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.


Molnupiravir

Facing a high-fatality FCoV-23 outbreak on the island nation of
Cyprus Cyprus (), officially the Republic of Cyprus, is an island country in the eastern Mediterranean Sea. Situated in West Asia, its cultural identity and geopolitical orientation are overwhelmingly Southeast European. Cyprus is the List of isl ...
, on 8 August 2023 the government released 80,000 anti-COVID
molnupiravir Molnupiravir, sold under the brand name Lagevrio, is an antiviral medication that inhibits the replication of certain RNA viruses. It is used to treat COVID19 in those infected by SARS-CoV-2. It is taken by mouth. Molnupiravir is a prodrug o ...
pills from its national
COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by the coronavirus SARS-CoV-2. In January 2020, the disease spread worldwide, resulting in the COVID-19 pandemic. The symptoms of COVID‑19 can vary but often include fever ...
stockpile, in a bid to solve the feline coronavirus crisis in a more cost-effective manner.


Immunostimulants

Immunostimulant Immunostimulants, also known as immunostimulators, are substances (drugs and nutrients) that stimulate the immune system usually in a non-specific manner by inducing activation or increasing activity of any of its components. One notable example i ...
s 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 In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
, the feline version feline interferon is more effective. An experimental polyprenyl
immunostimulant Immunostimulants, also known as immunostimulators, are substances (drugs and nutrients) that stimulate the immune system usually in a non-specific manner by inducing activation or increasing activity of any of its components. One notable example i ...
(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. 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.


Anti-inflammatory drugs

It is recommended to use an anti-inflammatory drug against FIP.
Immunosuppressive drug Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent the activity of the immune system. Classification Immunosuppressive drugs can be classifie ...
s dampen the immune system, helping to reduce
inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
. The go-to immunosuppressive drug in FIP is
prednisolone Prednisolone is a corticosteroid, a steroid hormone used to treat certain types of allergies, inflammation, inflammatory conditions, autoimmune disorders, and cancers, Electrolyte imbalance, electrolyte imbalances and skin conditions. Some of ...
, a
corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invo ...
. There are no placebo-controlled trials showing prednisolone to be better than other anti-inflammatories.


Prevention


Vaccination

There is no effective vaccine against FIPV.
DNA vaccination A DNA vaccine is a type of vaccine that transfects a specific antigen-coding DNA sequence into the cells of an organism as a mechanism to induce an immune response. DNA vaccines work by injecting genetically engineered plasmid containing the ...
with
plasmids A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria and ...
encoding FIPV proteins failed to produce immunity. Rather, it was observed that antibodies to the FIPV
spike protein In virology, a spike protein or peplomer protein is a protein that forms a large structure known as a spike or peplomer projecting from the surface of an viral envelope, enveloped virus. as cited in The proteins are usually glycoproteins that ...
exacerbate the disease.


In film

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. The film received an award at the 2018
Garden State Film Festival The Garden State Film Festival is a film festival in the United States held in Asbury Park, New Jersey, Asbury Park and Cranford, New Jersey, Cranford, New Jersey, which debuts more than 200 independent films annually over four days each spring. ...
in the Narrative Short category and was a Gold Kahuna winner at the 2018 Honolulu Film Awards.


See also

*
Feline leukemia virus Feline leukemia virus (FeLV) is a retrovirus that infects cats. FeLV can be transmitted from infected cats when the transfer of saliva or nasal secretions is involved. If not defeated by the animal's immune system, the virus weakens the cat's im ...
*
Feline vaccination Feline vaccination is animal vaccination applied to cats. Vaccination plays a vital role in protecting cats from infectious diseases, some of which are potentially fatal. They can be exposed to these diseases from their environment, other pets, or ...


Explanatory notes


References


External links


FIP Informational Brochure
from th
Cornell Feline Health Center

UC Davis Center for Companion Animal Health

FIP (Felipedia.org)
{{DEFAULTSORT:Feline Infectious Peritonitis Cat diseases Animal viral diseases Coronavirus-associated diseases