|
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. 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. 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
(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.
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. No matter what any laboratory or manufacturer of test kits claims, there is no single test for FIP – diagnosis is a challenge to even the most competent veterinary clinician and involves following a series of steps on an algorithm (download catvirus.com FIP flowchart). [The European Advisory Board of Cat Disease (ABCD) FIP algorithm was based on this flowchart (Addie et al, JFMS, 2009).] Diagnosing FIP consists of a number of steps as shown in the flowchart. Until you have a lot of experience in diagnosing FIP, you might find it useful to use the chart, and also the catvirus.com FIP diagnosis worksheet. 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 laboratory 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). In addition, most cats with FIP have a history of having had a stress of some sort – being neutered, rehomed, the introduction of a new kitten, 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)
To 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 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. To read about FCoV antibody tests in far greater detail, visit www.dr-addie.com/FCoVantibody.htm
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 effusionIn the USA, AGP testing kits can be obtained from Cardiotech Services. Enquiries to Jeff Sarno or call (502)473-7066.
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 but should become available from the University of Glasgow in the UK soon. 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 In addition, often bilirubin levels are raised, although other liver enzymes may be normal. FCoV antibody titre 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. To read about FCoV antibody tests in far greater detail, visit www.dr-addie.com/FCoVantibody.htm AGP level In the USA, AGP testing kits can be obtained from Cardiotech Services. Enquiries to Jeff Sarno Onras43@aol.com or call (502)473-7066.
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 In the USA, AGP testing kits can be obtained from Cardiotech Services. Enquiries to Jeff Sarno or call (502)473-7066.
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 Remember: a healthy cat with a FCoV antibody titre is NOT a cat with dry FIP.
For Step 5 of the algorithm - treatment - go to www.dr-addie.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 laboratories for FCoV and FIP tests
I'm sorry that I do not yet have recommendations for laboratories in all countries.
Veterinary Pathology Diagnostic Services University of Sydney George Tsoukalas Australian FCoV/FIP expert: Dr Jacqueline Norris BVSc, MVSt, PhD, Grad Cert Ed Stud (Higher), IVAS Cert Acup.
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 Pyrenees Maison Zabal 64470 Etchebar France
Send as much sample as you can (leftover samples are used in research).
FCoV antibody tests:Dr Joel Godenir LABORATOIRE
VETERINAIRE DEPARTEMENTAL Téléphone:
04 92 96 00 00 This laboratory declined to take part in the assessment, however I paid to have a few tests examined - there were some false positive results given.
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 effusions FCoV 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 Veterinaria University of Milan Via Celoria 10 20133 Milano Italy
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.
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.
Clinical Laboratory, University of Zurich, Winterthurerstr. 260, CH-8057, Zürich, Phone +41 44 635 81 11 Fax +41 44 635 89 06
To submit
a sample to the University of Glasgow for FCoV antibody testing or 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
Biobest have their own IFA (probably a type II FCoV) which works extremely well. Their test will feature in 2 future publications by D. Addie. Their contact is Dr Paul Burr. Biobest Laboratories Ltd Tel: +44 (0)131 440 2628 Email: enquiry@biobest.co.uk
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 Phone: 1 530 752 7991
FECV FA Cornell University College of Veterinary Medicine
AGP testing kits can be obtained from Cardiotech Services. Enquiries to Jeff Sarno Onras43@aol.com or call (502)473-7066.
This section has been moved to a new page.
Virus
detection by RT-PCR 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.
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:
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:
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!
last updated 5 October 2011 Site ©
2000 - 2011 Dr.
Diane D. Addie |