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What Is Feline Infectious Peritonitis (FIP)?

Feline infectious peritonitis (FIP) is the leading infectious cause of cat death. FIP occurs when the cat reacts inappropriately to feline coronavirus (FCoV) infection. Most cats simply become infected, shed FCoV for a month or two, mount an immune response, eliminate the virus and live happily ever after (see How to eliminate FCoV infection from a cattery or household of cats). However, for reasons that we don't yet fully understand, instead of clearing FCoV infection, an unfortunate few cats develop FIP.

The name FIP is slightly misleading: FIP isn't inflammation of the peritoneum (the lining of the abdomen) it is a vasculitis (inflammation of the blood vessels). The clinical signs which the cat develops depend on which blood vessels are damaged, and on which organ(s) the damaged blood vessels supplied.

Wet or effusive FIP
This is the acute form of the disease, where many blood vessels are damaged severely and fluid leaks out of them into the abdomen or the thoracic (chest) cavity. When the blood vessels in the abdomen are affected, the cat's tummy swells up with fluid called ascites. When the blood vessels in the thorax are damaged fluid leaks into the chest, impairing the ability of the lungs to expand and the cat shows difficulty breathing.

Dry or non-effusive FIP
Dry FIP is the more chronic form of the disease. In dry FIP, the cat often has vague clinical signs, such as going off his or her food, losing weight, the coat looking dull. Many cats with dry FIP become jaundiced (icteric), when you look inside the eyelid, it looks yellow. If the cat has a pale nose, you may notice that that looks yellow. Many cats with dry FIP get signs in their eyes: usually the iris (the coloured part of the eye around the pupil) changes colour, parts of it may appear brown (see photos).

(Many thanks to Mrs M. for this photograph.)
The cat may bleed into the eye, or white precipitates appear on the cornea (the clear membrane on the front of the eye).

For vets: check the eyes using an ophthalmoscope for vitreous flare and retinal vessel cuffing (see photo below).
(Many thanks to John Mould for this photograph.)

Around 12% of cats with non-effusive FIP develop neurological signs: often they become ataxic (wobbly and falling over when walking), they may have head tremors, fits, their eyes may dart from side to side instead of being focussed.

However, all of these clinical signs can be caused by other, sometimes treatable, conditions, which is why accurate diagnosis is essential.

Diagnosis of FIP - this section is intended for veterinary surgeons
FIP is a notoriously difficult condition to diagnose, many other conditions present with very similar clinical signs. Definitive diagnosis is only possible at post mortem, or occasionally by biopsy (though for accurate biopsy results one has to actually biopsy a visible pyogranulomatous lesion, which may necessitate laparotomy). Only 18% of samples sent to our laboratory for FIP diagnosis turn out to be FIP. Since cats with FIP are usually euthanased, it is absolutely vital that FIP is accurately differentiated from other, treatable, conditions.

In our laboratory at the University of Glasgow, we offer an FIP profile which confirms or rules out a diagnosis of FIP in over 90% of cases. The FIP profile consists of four parts: a feline coronavirus (FCoV) antibody titre, albumin:globulin (A:G) ratio on the effusion or plasma, alpha 1-acid glycoprotein (AGP) level and cytology or haematology.

Effusive ("wet") FIP profile

FCoV antibody titre
The presence of antibodies indicates that the cat has been infected with FCoV, the cause of FIP. Any FCoV antibody titre can occur in cases of wet or effusive FIP, but most cats with FIP have extremely high antibody titres (1280 or greater). Antibody titres of 0 are unusual in FIP cases and are usually considered as indicating that the cat does not have FIP. (However, if other parameters suggest a diagnosis of FIP, despite having an antibody titre of 0, then this is the one situation where FCoV RNA detection (RT-PCR), performed on a sample of the effusion, is diagnostic of FIP. In these cats there is so much virus in the effusion that all the antibody is bound to it, and none is available to bind to virus in the test.)

Note: many healthy cats and cats with diseases other than FIP have FCoV antibodies. The presence of FCoV antibodies alone is NOT diagnostic of FIP, if the other parameters of the profile do not indicate a diagnosis of FIP.

Total protein in the effusion and albumin:globulin ratio (A:G)
The total protein concentration in the effusion of a cat with FIP is usually greater than 35 g/l and this usually consists of more globulin than albumin, pushing down the A:G ratio. An A:G of < 0.4 indicates FIP is quite likely; an A:G of >0.8 rules out FIP; A:G of between 0.4-0.8 - consider other parameters. The A:G of an effusion is one of the most useful tests to perform in practice for a quick indicator of whether or not a cat may have FIP and can be performed on a VetTest machine (divide the albumin by the globulin values).

AGP level
Alpha one acid glycoprotein (AGP) is an acute phase protein which has been shown to be very useful in distinguishing FIP from other clinically similar conditions. In FIP, AGP levels are usually greater than 1500 mg/ml. In normal cats, it's up to 500 mg/ml. In cats with bacterial peritonitis or pleurisy the AGP is also raised, which is why cytology is also necessary to differentiate these conditions. In cardiomyopathy, non-infectious liver disease and tumours, which are the most common conditions mistaken for FIP, the AGP is normal.

In the USA, AGP testing kits can be obtained from Cardiotech Services. Enquiries to Jeff Sarno or call (502)473-7066.

Cytology
In effusive FIP, there are generally less than 3 x 10 9 nucleated cells per litre in the effusion and the cells are predominantly neutrophils and macrophages. In bacterial peritonitis and pleurisy, the white blood cell count in the effusion is much higher and the cytologist will usually see bacteria (if they are intracellular, this indicates that they were not simply contamination of the sample). Cytology of pleural effusions is useful for differentiation of thymic lymphosarcomas, since the predominant cell is the lymphocyte and they often appear malignant.

Summary
Thus, a cat with wet FIP should be FCoV seropositive, the total protein of the effusion must be over 35g/l and the albumin:globulin less than 0.4 (or at least less than 0.8), the AGP should be high (over 1500 micrograms/ml) and the cytology should reveal few nucleated cells which are mainly neutrophils and macrophages.

Non-effusive ("dry") FIP profile

FCoV antibody titre
FCoV antibody titres in dry FIP are usually equal to or greater than 1280. An antibody titre of zero rules out non-effusive FIP.

Note: many healthy cats and cats with diseases other than FIP have FCoV antibodies. The presence of FCoV antibodies alone is NOT diagnostic of FIP, if the other parameters of the profile do not indicate a diagnosis of FIP. A healthy cat with a high FCoV antibody titre is NOT a cat with dry FIP.

Albumin:Globulin ratio (A:G)
In FIP the globulin concentration in serum or plasma is raised to over 40g/l. Consequently the A:G is usually lowered. An A:G of < 0.4 indicates FIP is quite likely, provided that globulins are raised, remember than a low albumin (e.g. in liver disease) can also artificially lower the A:G. An A:G of >0.8 rules out FIP; A:G of between 0.4-0.8 - consider other parameters.

AGP level
AGP is an acute phase protein which is useful in distinguishing FIP from other clinically similar conditions. In FIP, AGP levels are usually greater than 1500 ug/ml. In normal cats, it's up to 500 ug/ml. Bear in mind, however, that AGP is not specific, and will also be raised if there is viral (non-FIP), bacterial (e.g. ascending cholangiohepatitis or pyelonephritis) or fungal infections or recent trauma. AGP measurement is useful in distinguishing FIP from neoplasia or non-infectious liver disease, when AGP levels will be normal.

In the USA, AGP testing kits can be obtained from Cardiotech Services. Enquiries to Jeff Sarno or call (502)473-7066.

Haematology
In non-effusive FIP there is lymphopenia, a non-regenerative anaemia with a haematocrit of 30% or less and often a neutrophilia with a shift to the left. Bear in mind that cats with other chronic infections can have similar haematological changes. Haematology is useful in differentiating FIP from Haemobartonella felis infection where the anaemia is regenerative and there may be organisms visible on the erythrocytes.

Summary
A cat with dry FIP should have a high FCoV antibody titre, be hyperglobulinaemic and have a reduced albumin:globulin ratio. He or she should have a high AGP, lymphopenia, a haematocrit of less than 30% which is non-regenerative and possibly a neutrophilia. Clinically, the cat should have lost weight and will usually have ocular signs such as iritis, retinal vessel cuffing, keratic precipitates, aqueous or vitreous flare.

Remember: a healthy cat with a FCoV antibody titre is NOT a cat with dry FIP.

Recommended laboratories for FCoV and FIP tests

Recommendations not availble for all countries.

France

FCoV antibody tests:
Dr Joel Godenir
LABORATOIRE VETERINAIRE DEPARTEMENTAL
105, route des Chappes
BP 107
06902 SOPHIA ANTIPOLIS Cedex
FRANCE

Téléphone: 04 92 96 00 00
Fax: 04 92 96 01 20

Cost: 21 euros HT, (25.12 euros tax included)

RT-qPCR to test for virus:

Scanelis laboraty.

Switzerland

RT-qPCR to test for virus:
Zurich Veterinary School

United Kingdom

To submit a sample to the University of Glasgow for a FIP profile

Note that the FIP profile is NOT for use in healthy cats. To screen a healthy cat for exposure to FCoV, simply send a heparin blood sample for a FCoV antibody titre.

Effusive or wet FIP: send 1ml heparin blood and 1-2ml effusion in plain and EDTA tubes. (Note: sending the effusion will greatly increase the chances of an accurate diagnosis.)Non-effusive or dry FIP: send 2 x 1ml heparin blood and 1 ml EDTA blood and two air-dried blood smears.

Send samples with a test request form (can be downloaded from Companion Animal Diagnostics or obtained by calling UK 0141 330 5777) or with a note of your address to:

    Companion Animal Diagnostics
    University of Glasgow Veterinary School
    Bearsden
    Glasgow
    G61 1QH
    UK

United States of America

RT-qPCR to test for virus:

Dr Christian Leutenneger's laboratory, the Lucy Whittier Molecular and Diagnostic Core Facility. You can download a sample submission form from his website.

AGP testing kits can be obtained from Cardiotech Services. Enquiries to Jeff Sarno Onras43@aol.com or call (502)473-7066.

Feline coronavirus antibody tests

It is essential that your veterinary surgeon use a RELIABLE FCoVantibody test such as the immunofluorescent antibody test we use at the University of Glasgow. Not all tests are comparable with ours.

In our laboratory, we found that the FCoV Immunocomb, by Biogal Galed Laboratories, compared very favourably with our antibody test. This finding was presented at the Second International Feline Coronavirus/Feline Infectious Peritonitis workshop and the abstract is available on that website if anybody wishes further information. The full paper is published in the April 2004 edition of the Journal of Feline Medicine and Surgery. The Immunocomb is an antibody test which can be used in the veterinary surgery.

(Please note that although Biogal Galed have a link from this website, I am in no way an employee of theirs, nor a shareholder. They did fund the study in which their test was evaluated, but in the full understanding that I would publish my findings whether or not the results were favourable. I remain impartial - I make no personal gain from Biogal, nor do they donate to my research. Their link is there because I personally approve of their FCoV Immunocomb product. They are charged the same as other advertisers, but their fee goes to the Celia Hammond Animal Trust, a charity which rescues cats.)

Note to FCoV antibody test manufacturers: I am happy to discuss evaluation of your antibody tests at any time.

Use of FCoV antibody tests

  1. Diagnosis of FIP (see FIP diagnosis above)
    Good antibody tests are incredibly useful in the diagnosis of FIP, most cases of FIP have very high titres and a negative test can often rule out a diagnosis of FIP. Occasionally, an effusive FIP will seem to be antibody negative because there is so much virus in the cat that all the antibody is bound to that and not available to bind to the virus in the test.

    A frequently asked question is: can antibody tests differentiate feline enteric coronavirus from FIP virus? It's not a good question, because wherever FCoV is, FIP can develop. No consistent genetic or serological difference has ever been found in viruses from cats with FIP compared with viruses from healthy cats.
  2. Testing cat(s) who have been in contact with a cat suspected of excreting FCoV
    These cats are very likely to have antibody to FCoV, since it is an extremely infectious virus. However, testing can be useful to obtain an antibody titre which can be used for comparison, when in 2-3 months a repeat test is taken to determine whether the antibody titre is declining. Obviously if the cat's antibody titre is less than 10 (i.e. negative) it is good news - the cat won't develop FIP and isn't shedding FCoV, so it is safe to get a new feline friend to keep him or her company!

    Knowing that a cat is FCoV antibody positive can enable you to reduce stress on the cat in an attempt to prevent FIP.
  3. Testing before mating with a known positive or negative cat

    It is important that cat breeders avoid infecting their own or another person's cats by only mating antibody positive cats to antibody positive cats, and antibody negative cats to antibody negative cats.
  4. Screening a household for the presence of FCoV
    Since FCoV is highly infectious, it is not always necessary to test all the cats in a household to establish whether or not FCoV is present: if the cats are in groups, then only a sample from each group need be tested. Usually, when FCoV is endemic, over 90% of the cats have antibodies. In control programmes, the cats are tested every 2-3 months and as cats' antibody titres decline to zero, they are put in with the negative group to prevent re-infection.
  5. Screening a cat for introduction into a FCoV-free household
    Once a household is FCoV-free, it is vital to stay that way, so all new cats and kittens need to be tested antibody negative before being introduced. It may even be sensible to quarantine and test cats coming back from stud or shows.

Virus detection by RT-PCR
See also What is RT-PCR. RT-PCR detects the FCoV genome, so indicates presence of the virus. However, interpretation of such tests is difficult: healthy cats as well as cats with FIP can be positive for the virus. Also, cats with illnesses other than FIP can co-incidentally have the virus.

In my research survey, I found that it was less useful to use RT-PCR than our antibody test: to show that a cat has eliminated FCoV required only one antibody titre of less than 10 in our laboratory, but required 5 monthly negative RT-PCR tests on faeces. However, RT-PCR remains the only way to detect a carrier cat - a cat who sheds FCoV continually for 9 months or more is likely to be a lifelong carrier.

At time of writing, there is no RT-PCR which can differentiate FIP-causing coronaviruses from coronaviruses which do not cause FIP. The difference between the former and the latter is that in FIP, the FCoV can replicate in macrophages, whereas in FCoV infected cats without FIP, FCoV is not replicating in macrophages. (Replicate means multiply, macrophages are a type of white blood cell.) However, at the Second International Feline Coronavirus/Feline Infectious Peritonitis workshop, a young Dutch scientist, Fermin Simons, presented an RT-PCR he is working on which detects replicating FCoV in macrophages, his abstract is on the SIFFS website. This RT-PCR is not presently commercially available, but is a very promising test for the diagnosis of FIP.

In America, the FCoV RT-qPCR test which I would recommend you use is available from Dr Christian Leutenneger's laboratory. You can download a sample submission form from his website.

Treatment of FIP - this section is intended for veterinary surgeons

What clinical signs (symptoms) should I look out for in my cat?

Any of the following clinical signs should alert you to the possibility of your cat developing FIP:

  • weight loss
  • recurring fevers (usually detected when your veterinary surgeon takes the cat's temperature)
  • going off food
  • the cat becomes even lazier than usual
  • sudden swelling of the abdomen
  • look closely at your cat's eyes regularly, watch for any change in colour of the iris (the coloured area of the cat's eye around the pupil) or any cloudiness, or bleeding (look closely at the cats' eyes in the Dry or non-effusive FIP section to get an idea of what you are looking for)
  • difficulty breathing (the cat breathing through his or her mouth)
  • if the cat has a fit or seizure
  • if the cat seems to lose balance, become clumsy
  • if the cat's personality changes

If you are a cat breeder, the following signs in your kittens should alert you to the possibility of FCoV being present in your cats:

  • kittens of uneven size in a litter
  • diarrhoea in kittens around 5-7 weeks of age
  • transient sneezing or discharge from the eyes in young kittens
Remember that all of the clinical signs described above can occur due to other, curable, conditions, so take your cats to your veterinary surgeon to be checked if any of these signs occur and hope for the best. Remember that 8 out of 10 cats whose samples were sent to our laboratory for FIP diagnosis turned out not to have FIP at all!

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