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Feline infectious peritonitis (FIP) is the name given to a common and aberrant immune response to infection with
feline coronavirus Feline coronavirus (FCoV) is a positive-stranded RNA virus that infects cats worldwide. It is a coronavirus of the species '' Alphacoronavirus 1'' which includes canine coronavirus (CCoV) and porcine transmissible gastroenteritis 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 The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
coronavirus (FECV). From the gut, the virus very briefly undergoes a
systemic Systemic fundamental to a predominant social, economic, or political practice. This refers to: In medicine In medicine, ''systemic'' means affecting the whole body, or at least multiple organ systems. It is in contrast with ''topical'' or ''loc ...
phase, before returning to the gut where it is shed in the feces. The
pathogenesis 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 from Greek πάθος ''pat ...
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 conventional 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 transmission

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 agricultural communities, where stray livestock would ...
s, etc.). The virus is shed in feces, and cats become infected by ingesting or inhaling the virus, usually by sharing
cat litter A litter box, also known as a sandbox, cat box, litter tray, cat pan, potty, pot or litter pan, is an indoor feces and urine collection box for cats, as well as rabbits, ferrets, miniature pigs, small dogs, and other pets that instinctively or ...
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, they leave their contaminated saliva on the fur. Later, when the healthy cat goes to groom themselves, they ingest the contaminated saliva and then become infected.


Clinical signs

There are two main forms of FIP:
effusive In physics and chemistry, effusion is the process in which a gas escapes from a container through a hole of diameter considerably smaller than the mean free path of the molecules. Such a hole is often described as a ''pinhole'' and the escape ...
(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 Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showin ...
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 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 abnormal heme meta ...
, 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 Eyes are organs of the visual system. They provide living organisms with vision, the ability to receive and process visual detail, as well as enabling several photo response functions that are independent of vision. Eyes detect light and conv ...
or
neurological Neurology (from el, νεῦρον (neûron), "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 brain, the spinal c ...
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 ch ...
(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 35g/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 the proteins of the albumin family are water- soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Album ...
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 natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ada ...
(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 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) but, despite investigations by a physician, no explanation has been found.
; intra-ocular signs; jaundice. # Biochemistry:
hypergammaglobulinaemia Hypergammaglobulinemia is a medical condition with elevated levels of gamma globulin. It is a type of immunoproliferative disorder. Types Hypergammaglobulinemia is a condition that is characterized by the increased levels of a certain immunoglo ...
; raised
bilirubin Bilirubin (BR) ( Latin for "red bile") is a red-orange compound that occurs in the normal catabolic pathway that breaks down heme in vertebrates. This catabolism is a necessary process in the body's clearance of waste products that arise from t ...
without liver enzymes being raised. #
Hematology Hematology ( always 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 blood. It involves treating diseases that affect the produc ...
:
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 ...
; non-regenerative—usually mild—
anaemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...
. #
Serology Serology is the scientific study of serum and other body fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum. Such antibodies are typically formed in response to an infection (against a given mic ...
: 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 Affinity chromatography is a method of separating a biomolecule from a mixture, based on a highly specific macromolecular binding interaction between the biomolecule and another substance. The specific type of binding interaction depends on the ...
(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 An immune disorder is a dysfunction of the immune system. These disorders can be characterized in several different ways: * By the component(s) of the immune system affected * By whether the immune system is overactive or underactive * By whether t ...
, treatment falls into two categories: direct action against the virus itself and modulation of the immune response.


Antiviral drugs


Immunostimulants

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 Interferon alfa-2b is an antiviral or antineoplastic drug. It is a recombinant form of the protein Interferon alpha-2 that was originally sequenced and produced recombinantly in ''E. coli'' in the laboratory of Charles Weissmann at the Universi ...
. 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 or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respon ...
, the feline version feline interferon is more effective. 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. 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.


Antivirals

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. Unlike most antibiotics, antiviral drugs do n ...
s (in the narrow sense) act by interfering with the enzymes or other biological processes in the FIP virus. 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 ...
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 in order to test claims of causal relationships. Random assignment help ...
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 2019) commercially available in the United States, this study is considered very promising and may lead to commercially available medication for the treatment of FIP. GS-441524 is available at >99% purity commercially from
research chemical Research chemicals are chemical substances used by scientists for medical and scientific research purposes. One characteristic of a research chemical is that it is for laboratory research use only; a research chemical is not intended for human o ...
suppliers such as Selleckchem, MedKoo and MedChemExpress. An experimental antiviral drug called GC376 was used in a field trial of 20 cats: 7 cats went into remission, and 13 cats responded initially but relapsed and were euthanized. This drug is not yet (as of 2017) commercially available.


Anti-inflammatory drugs

It is generally recommended to use an
anti-inflammatory drug Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as op ...
against FIP.
Immunosuppressive drug Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system. Classification Immunosuppressive drugs can be classified int ...
s dampen the immune system, helping to reduce
inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...
. The go-to immunosuppressive drug in FIP is
prednisolone Prednisolone is a steroid medication used to treat certain types of allergies, inflammatory conditions, autoimmune disorders, and cancers. Some of these conditions include adrenocortical insufficiency, high blood calcium, rheumatoid arth ...
, 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 inv ...
. 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 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; how ...
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 enveloped virus. as cited in The proteins are usually glycoproteins that form dimers or ...
exacerbate the disease.


Prevention

Kittens are protected from infection by maternally derived antibody until weaning, usually around 5–7 weeks of age; therefore, it is possible to prevent infection of kittens by removing them from sources of infection. However, FCoV is a very contagious virus and such prevention does require rigorous hygiene.


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 which debuts more than 200 independent films annually over four days each spring. The festival was founded in 2002 in Sea Girt, New Jersey by ...
in the Narrative Short category and was a Gold Kahuna winner at the 2018
Honolulu Film Awards The Honolulu Film Awards (HFA) are international film awards granted to independent films in Honolulu, Oahu, Hawaii, United States. Winners 2012 *Grand Jury Award: '' Irvine Welsh's Ecstasy'' (Director: Rob Heydon) *Special Jury Award: '' Men ...
.


See also

* Feline vaccination *
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 ...


References


External links


Feline Infectious Peritonitis and Coronavirus Website

Why Do Cats Purr? Is It Good Or Bad?
- Two Cat Freaks Blog

from vetinfo.com
Research on Feline Infectious Peritonitis
from University of Tennessee, College of Veterinary Medicine


FIP Informational Brochure
from th
Cornell Feline Health Center

UC Davis Center for Companion Animal Health

Animal Health Channel



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