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Feline infectious peritonitis (FIP) is the leading infectious cause of cat death. FIP occurs when there is an excessivly inflammatory immune response to feline coronavirus (FCoV) infection. Most cats simply become infected, shed FCoV for a a few months, 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. The key event in the development of FIP is the infection of the monocyte (a white blood cell) by feline coronavirus (FCoV). From the moment of infection of the monocyte, the cat’s fate hangs on whether or not that monocyte can contain the virus and eventually defeat it, or whether the virus wins, and begins replicating within the monocyte [Dewerchin et al, 2005]. In the animation shown below, we depict the latter. We show how the virus hijacks the immune system, leading to an inflammatory sequence of events which results in a pyogranuloma forming around a blood vessel. In the film we show the development of acute FIP, where there is a lot of virus, many blood vessels affected, and the resulting leakage from damaged blood vessels causes the clinical signs of effusive FIP – ascites, thoracic effusion, pericardial effusion. In non-effusive FIP the course is more chronic: fewer blood vessels are affected, the cat’s immune system tries harder to contain the infection, leading to larger pyogranulomata and the clinical signs of chronic inflammation and relating to the organ(s) containing the pyogranulomas. I am very grateful to Dr Francois Bagaini, of vetocyte.fr for making this animation for me:
Wet
or effusive FIP 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. Dr Greg Martinez made a good YouTube film to show this: The thoracic form of wet FIP is less acute than the abdominal form, and some cats with thoracic FIP can survive many weeks or months. Dry or non-effusive
FIP
(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 Download catvirus.com FIP flowchart Download catvirus.com FIP diagnosis worksheet. The rest of this section will take you step by step through the FIP diagnosis flowchart: Step 1: The cat's history is consistent with a diagnosis of FIP Step 2: Clinical examination suggests either effusive or non-effusive FIP as a possible diagnosis Step 3: Effusive (“wet”) FIP - analysis of the effusion Step 4: Non-effusive ("dry") FIP - analysis by a specialist laboratoryExample of using the catvirus.com FIP diagnostic algorithm: Case history - Does Pancho have Non-effusive FIP? To submit a sample to the University
of Glasgow for a FIP profile
Step 1: The cat's history is consistent with a diagnosis of FIP There are usually 2 key aspects in the cat's history which suggest that FIP is a possible diagnosis of his or her presenting signs: first the cat MUST have become infected with feline coronavirus (FCoV) in order to have developed FIP, therefore there will be a history of having been in a multicat environment, such as at a cat breeder's, or a rescue shelter, within the previous 18 months. (Development of FIP more than 18 months after infection would be very unusual, though does occur in geriatric cats or immunosuppressed cats, e.g. cats undergoing chemotherapy, or cyclosporine A (Atopica, Novartis) treatment, or after becoming infected with feline leukaemia virus or feline immunodeficiency virus. A cat living indoors alone all his or her life will be very unlikely to have developed FIP (though check for a history of having stayed in a boarding cattery, or some other opportunity for exposure – e.g. recent adoption of a kitten). M ost cats with FIP have a history of having had a stress of some sort – being neutered, rehomed, the introduction of a new kitten, even something as simple as a booster vaccine (Addie et al, 2020)etc. Incubation for effusive FIP is usually a few days up to one month. The incubation period for non-effusive FIP can be up to a year. FIP is most common on first exposure to the virus - if a cat has been infected with FCoV for over a year, it is unlikely he or she will develop FIP. Step 2: Effusive (“wet”) FIP - clinical signs Effusive FIP is the more acute condition – occurring within 4-6 weeks of a stressful event in the cat’s life, whereas non-effusive FIP can incubate for months to years. If you understand that FIP is an immune-mediated vasculitis it becomes easier to understand how it is able to manifest with so many varied clinical signs. Any blood vessel to any organ can be affected and the clinical signs will result from damage to that organ. In effusive FIP, many blood vessels are affected, allowing fluid to leak out into the abdomen, thorax or pericardium. Thus the cat presents with ascites or pleural or pericardial effusion. The ascitic cat may appear to have put on weight, although ribs are usually more palpable. The Orion Foundation call FIP “the purring disease” because the cat may still be bright and eating, though some are dull and anorexic. The temperature of cats with FIP rarely exceeds 103oF (39oC). A cat with a pleural effusion will present with dyspnoea. Step 3: Effusive (“wet”) FIP - analysis of effusion Total protein in the effusion and albumin:globulin ratio (A:G) FCoV antibody test in the effusion Alpha one acid glycoprotein (AGP) Rivalta testTo perform a Rivalta test, take 10 mls of water (must be at room temperature), add 2-3 drops of 8% acetic acid (ordinary clear/white vinegar) and carefully layer a drop of the effusion into it. If the effusion dissipates like a wisp of smoke in air the Rivalta test is negative and the cat is 97% not likely to have FIP. If, however, the effusion hangs from the surface in a globule, then slowly floats down like a jellyfish, the Rivalta test is positive. A positive Rivalta test means that the cat is 86% likely to have FIP (i.e. 5 of 6 cats with a positive Rivalta test do have FIP, so clearly other tests need to be performed to be more certain of the diagnosis).Watch a film of the Rivalta test:
Reference: Total protein in the effusion
and albumin:globulin ratio (A:G) Cytology . FCoV antibody titre Step 4: Effusive (“wet”) FIP - analysis of effusion by a specialist laboratory Alpha one acid glycoprotein (AGP) Virus detection in macrophages (IF) positive Virus RNA detected by RT-PCR in the effusionAGP level Virus detection in macrophages by direct immunofluorescence or immunohistochemistry Detection of FCoV in macrophages in an effusion by direct immunofluorescence is diagnostic of FIP, but a negative result is more difficult to interpret (Hartmann et al, 2003). This test is not currently widely available. Viral RNA detected by RT-PCR in the effusion Reverse transcriptase polymerase chain reaction (RT-PCR) detects the RNA of the FCoV – i.e. is a test which detects actual virus. Quantitative RT-PCR (RT-qPCR) is an interesting recent development in which the amount of virus in the sample may be measured. RT-PCR is useful in control of FCoV infection in households of healthy cats and is useful in FIP diagnosis on organs of cats in biopsy or post mortem specimens. Detection of FCoV RNA in the blood or faeces is not diagnostic of FIP, since some healthy FCoV antibody positive cats, or animals with non-FIP illness, are also positive. In addition, cats with FIP may be negative – the effusion of cats with FIP is often negative. Summary Step 2: Non-effusive (“dry”) FIP - clinical signs If you understand that FIP is an immune-mediated vasculitis it becomes easier to understand how it is able to manifest with so many varied clinical signs. Any blood vessel to any organ can be affected and the clinical signs will result from damage to that organ. FIP is generally defined as either “wet” (effusive) or “dry” (non-effusive) but neither is clear cut and an effusive case can become non-effusive or vice versa. Effusive FIP is the more acute condition – occurring within 4-6 weeks of a stressful event in the cat’s life, whereas non-effusive FIP can incubate for months to years. In the longer incubating non-effusive, FIP, fewer blood vessels are affected than in effusive FIP and the immune response is more chronic, leading to larger pyogranulomata. The cat loses weight gradually, is chronically pyrexic, and becomes dull and anorexic. Most cats with dry FIP have palpably enlarged mesenteric lymph nodes and intraocular lesions. Clinical signs will depend on which organs are involved:
Step 3: Non-effusive (“dry”) FIP blood sample Haematology - reveals a non-regenerative anaemia and lymphopenia Hypergammaglobulinaemia causing low albumin:globulin (A:G) ratio Alpha 1 acid glycoprotein (AGP) in non-effusive FIP diagnosis Haematology reveals a non-regenerative anaemia and lymphopenia Hypergammaglobulinaemia causing low Albumin:Globulin ratio
(A:G) ratio FCoV antibody titre AGP level Step 4: Non-effusive (“dry”) FIP - analysis by a specialist laboratory Alpha one acid glycoprotein (AGP)Virus RNA detected by RT-PCR in the effusion AGP level Reverse transcriptase polymerase chain reaction (RT-PCR) detects the RNA of the FCoV – i.e. is a test which detects actual virus. Quantitative RT-PCR (RT-qPCR) is an interesting recent development in which the amount of virus in the sample may be measured. RT-PCR is useful in control of FCoV infection in households of healthy cats and is useful in FIP diagnosis on organs of cats in biopsy or post mortem specimens. Detection of FCoV RNA in the blood or faeces is not diagnostic of FIP, since some healthy FCoV antibody positive cats, or animals with non-FIP illness, are also positive. In addition, cats with FIP may be negative – the blood of cats with FIP is usually negative. In non-effusive FIP, detection of large amounts of virus in a fine needle aspirate of a mesenteric lymph node is highly indicative of FIP. However, detecting FCoV in the CSF of cats is not diagnostic – healthy cats and cats with non-FIP conditions are occasionally positive (detecting FCoV antibody in the CSF is more useful). Summary For Step 5 of the algorithm - treatment - go to www.catvirus.com/treatment.htm Example of using the catvirus.com FIP diagnostic algorithm: Case history Does Pancho have Non-effusive (“dry”) FIP? (Note to veterinary surgeons - this video counts for 15 minutes continuing professional development.) Recommended veterinary surgeons with specialist FIP and FCoV knowledge This list is very much in its infancy and so far the majority of recommended FIP specialist veterinarians are in the UK. Japan Dr Yasuda Hidemi BVSc. http://yasuda-vet.org/clinic.html You Me Animal Clinic, Sakura-shi, Japan. Dr Katayama, Bloom Animal Hospital, Kajiyama 1-10-32, Tsurumi, Yokohama City 230-0072, Japan.
UK Dr Charlotte Aston: has experience treating effusive FIP and FCoV shedding monitoring. Charlotte impresses me with the way she cares intensely about her patients. Tel. No. 01664 560364 Dr Mark Fosbery, BVMS BSc (Hons) MRCVS Newnham Court Veterinary Hospital Website: www.newnhamvets.co.uk
Dr John Mould, BA, BVSc, DVOphthal, FHEA, MRCVS: veterinary ophthalmologist. It was John who taught me about the intra-ocular signs of FIP and many of the eye photos I use on the website and in my lectures come from him. John is compassionate, thorough, knowledgeable. Veterinary surgeons: if you need pathology on an eye, send it to the Eye Veterinary Clinic and get advice about how to preserve it first: don't stick the eye in formalin.
Email: info@eyevetclinic.co.uk Dr Jacques Penderis, BVSc MVM PhD CVR DipECVN MRCVS: neurology consultant with enormous FIP experience and expertise. Dunblane Clinic | Tel: 01786 824 400 Sherwood Vets in Ashford and Hampton, England.
Dr Elise Robertson BS BVetMed MACVSc (Feline) DipABVP (Feline) MRCVS USA Jerry Murray DVM Jerry is an expert in felne and ferret coronavirus and infectious peritonitis.
Recommended laboratories for FCoV and FIP tests I'm sorry that I do not yet have recommendations for laboratories in all countries. Japan Russia Veterinary Pathology Diagnostic Services University of Sydney George Tsoukalas RT-qPCR to test for feline coronavirus:Scanelis laboratory. IFA using TGEV:Contact: Dr Sophie de Poder UMR 1161-Virologie, Ecole Nationale Vétérinaire d'Alfort, 7 avenue du Général de Gaulle,94704 Maisons-Alfort, France.Dr Addie's laboratory: Feline Institute PyreneesMaison Zabal64470 EtchebarFranceSend as much sample as you can (leftover samples are used in research). FCoV antibody
tests:Dr Joel GodenirLABORATOIRE
VETERINAIRE DEPARTEMENTAL Téléphone:
04 92 96 00 00 Italy boasts more than its share of FCoV experts: AGP testing and immunofluorescence of macrophages in effusion - Prof. Saverio Paltrinieri is the world expert in feline alpha 1-acid glycoprotein (AGP) and he and his colleague developed the technique of direct fluorescence in macrophages in effusionsFCoV RT-PCR - Dr Nicola Decaro (this young man is the world expert in canine coronavirus!) FCoV antibody testing - Dr A. Pratelli (email: a.pratelli@veterinaria.uniba.it) Prof. Saverio Paltrinieri's laboratory: Dipartimento di Patologia Animale Igiene e Sanità Pubblica VeterinariaUniversity of MilanVia Celoria 1020133 MilanoItaly Drs Decaro and Pratelli are based at the University of Bari. The University of Bari laboratory uses their own quantitative RT-PCR for detection of coronavirus. They developed their own antibody ELISA cited in Pratelli et al, 2008 and Pratelli et al, 2009 and has the technology to do immunofluorescence, virus neutralisation testing and western blotting. They are also able to differentiate IgA and IgG. I highly recommend this laboratory.Department of Public Health and Animal Sciences, Faculty of Veterinary Medicine, University of Bari, Italy. Switzerland This is the laboratory of world renowned FCoV/FIP expert Prof. Hans Lutz and is run by another expert and highly efficient scientist: Dr Marina Meli. It was in this laboratory that the first RT-qPCR to detect FCoV was developed. They also offer a TGEV indirect immunofluorescent antibody test. Zurich Veterinary School Clinical Laboratory, University of Zurich,Winterthurerstr. 260, CH-8057, Zürich, To submit
a sample to the University of Glasgow for FCoV antibody testing or FIP profile 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 Veterinary Diagnostics Services or obtained by calling UK 0141 330 5777) or with a note of your address to: Veterinary Diagnostics Services Download a sample submission form here. (It will open in a new tab.)
Biobest have their own IFA (probably a type II FCoV) which works extremely well. Their FCoV antibody test was featured in three peer-reviewed publications and compared favourably in an independent study. Their contact is Dr Paul Burr. Biobest Laboratories Ltd Email: enquiry[at]biobest.co.uk
Pinmoore Laboratories are not recommended: they would not divulge which FCoV RT-PCR they use and seem to be unable to give virus quantity.
Lucy Whittier Molecular and Diagnostic Core Facility. This is the veterinary diagnostic laboratory of the legendary Dr Niels Pedersen - the number 1 world expert on FIP! He is also the man who discovered Feline Immunodeficiency Virus! You can download a sample submission form from the website. Lucy Whittier Molecular & Diagnostic Core Facility Cornell University College of Veterinary Medicine Antech Laboratories are NOT recommended
AGP testing kits can be obtained
This section has been moved to http://www.catvirus.com/FCoVantibody.htm. Virus
detection by RT-PCR However, you cannot use RT-PCR results on faeces to diagnose FIP because cats with illnesses other than FIP can co-incidentally have coronavirus in their faeces. In my research survey, I found that it was less useful to use RT-PCR than a sensitive FCoV 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. My belief is that all feline coronaviruses are capable of causing FIP, if the cat is exposed to a high enough dose or if the cat is immunosuppressed, for example by long-term corticosteroid use, or concurrent feline leukaemia virus infection. 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:
Addie D.D., Jarrett O. 1992. A study of naturally occurring feline coronavirus infection in kittens. Vet. Rec. 130: 133-137. Addie D.D., Jarrett O. 1992. Feline coronavirus antibodies in cats. Vet. Rec. 131: 202-203. Addie D.D., Toth S. 1993 Feline coronavirus is not a major cause of neonatal kitten mortality. Feline Practice 21: (5) 13-18. Addie DD, McDonald M, Audhuy S, Burr P, Hollins J, Kovacic R, Lutz H, Luxton Z, Mazar S, Meli M. 2012 Quarantine protects Falkland Islands (Malvinas) Cats from Feline Coronavirus Infection. J Feline Med Surg. 14 2 171-176. Addie DD, le Poder S, Burr P, Decaro N, Graham E, Hofmann-Lehmann R, Jarrett O, McDonald M, Meli ML. 2015. Utility of feline coronavirus antibody tests. J Feline Med Surg. 17(2):152-62. Meli ML, Burr P, Decaro N, Graham E, Jarrett O, Lutz H, McDonald M, Addie DD. 2013. Samples with high virus loads cause a trend toward lower signal in feline coronavirus antibody tests. J Feline Med Surg. 15: (4) 295 – 299.
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