Imagine a disease that is infectious yet not contagious, has 100% mortality, virtually no diagnostic test to confirm it, and no effective treatment. When FIP becomes a possibility for a pet cat, questions abound yet not nearly enough are answered plus there is a great deal of older information still circulating. We decided to cover some basics here.
What is FIP?
Feline infectious peritonitis is a syndrome that results from widespread infiltration of the body’s organs with a type of inflammatory tissue called pyogranuloma. The resulting global inflammation leads to the failure of the infiltrated organs, fevers unresponsive to antibiotics, and often an accumulation of thick yellow fluid in the belly or chest. As noted, the “wet” form of FIP includes the thick, yellow fluid. The “dry” form is more insidious, leading to death over a much longer period (potentially years, but usually weeks to months.) Symptoms still involve fevers and poor appetite with the dry form, but also commonly involve deep inflammation in the eyes and nervous system. Both the wet and dry forms have been felt to have 100% mortality, though recently some newer treatments have brought some hope.
Is FIP Contagious?
Very simply, the answer is no. FIP stems from infection with the enteric coronavirus of cats, but FIP is not contagious.
How Can an Infectious Disease not be Contagious?
A contagious disease is spread from animal to animal or person to person. The feline enteric coronavirus is contagious, but most cats that get infected just get temporary flu-like symptoms (fever, diarrhea, malaise). FIP is a special reaction to infection with the feline enteric coronavirus. Whether a cat gets this devastating reaction to a normally harmless virus is more a function of the individual cat than the virus. The virus is contagious but a cat cannot transmit FIP to another cat.
Transformation of Coronavirus into FIP Virus
The process of the immunological defeat of the virus involves a cell called a macrophage. The macrophage consumes infected material and packages it in special structures that are then flooded with acids and digestive enzymes thus destroying the package contents. Any virus inside the package is killed by this process and its components are then used by the immune system to help mount a specific immunological reaction (i.e., make the proper antibodies, send specific killer cells, etc.) against further viruses.
What do we Know about the Feline Enteric Coronavirus?
Some basics about this virus are:
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It is common wherever cats are housed in groups and it is readily transmitted between cats.
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Transmission is typically by contact with infected feces. This means that the litter box is the usual place where infection takes place. Coronavirus infection is unusual in cats that free-roam outdoors (no litter box) or live in homes with only one cat.
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An active infection lasts several weeks to a few months. The virus is shed in the infected cat’s stool during this period. If the cat is reinfected, the virus sheds again for weeks to months. During this time, the cat may or may not seem at all ill. Some infected cats do not shed the virus.
- Most household disinfectants readily kill coronavirus immediately. Room temperature kills coronavirus within 48 hours. Carpeting is protective against the virus and the virus can survive in carpeting for at least seven weeks.
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Once a cat has been infected with the virus and recovered, the cat can be easily re-infected by continued exposure to infected feces. In this way, many catteries where there are always cats sharing litter boxes never rid themselves of this infection.
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The enteric coronavirus attacks intestinal cells and creates GI upset. As long as the infection is confined to the GI tract, there will be no FIP.
Cats in Box Graphic
Graphic by MarVistaVet
The process of the immunological defeat of the virus involves a cell called a macrophage. The macrophage consumes infected material, packaging it in structures that it floods with acids and digestive enzymes. Any virus is killed by this process and its components are then used by the immune system to help mount a specific immunological reaction (i.e. make the proper antibodies, send specific killer cells, etc.)
In some cats, a mutation occurs in the coronavirus. This mutation occurs during infection and allows the virus to survive the treatment by the macrophage. Instead of being killed by the macrophage, the virus essentially uses the macrophage to hitch a ride into the body’s core. The macrophage response mounts an attempt to kill the virus but ends up producing heaps of ineffective macrophages and immunologic proteins, which make up an immunologic tissue called a pyogranuloma. FIP is the infiltration of normal organs with pyogranulomas.
The mutation to a form of the virus that can cause FIP is more likely to occur in a cat with a compromised immune system. Most cats with FIP are under age 1 year (their immaturity is their immune compromise). Crowding is also an important source of immune compromise. Another important factor in mutation is multiple exposure/infections. When cats keep getting reinfected the virus they carry has more chance of mutating to a form that causes FIP.
Factors that increase the chance of coronavirus mutation include:
- Genetics
- Early weaning
- Overcrowding
- Age at the time of coronavirus infection
- Surgery stress (usually spay/neuter)
- Sharing litter box with other cats
Why isn’t the Mutated Virus Contagious?
We do not know why. We can inject fluids from a cat with FIP into a normal cat and cause FIP but short of this kind of experimental transmission, the mutated virus doesn’t seem to make it into the natural external secretions of an infected cat. This effectively confines the mutated virus inside the sick cat’s body, though the sick cat will still shed the non-mutated virus. It appears that genetics plays a large role in the mutation of the virus with every FIP cat developing its unique mutation. A virus that causes FIP in one cat may not do so in another cat.
How is it Possible there is no Test for this Classical Disease?
We used to think that the difference between getting the flu and getting FIP was all about the strain of the virus with which a cat gets infected. Lots of time and effort were spent trying to determine what made the FIP virus special. We no longer think there is a “special” strain of virus that causes FIP. FIP results, as described above, from a mutation that occurs in the virus after the infection has occurred. It's even more complicated: there isn't only one mutation that transforms regular coronavirus into the FIP virus. Many mutations can do it and we may not even have identified all of them. Whether or not these mutations occur in any given infection, cases seem to relate more to the immune status of the cat than any factor in the virus. The more virus there is replicating, the greater the chance of one of the FIP mutations occurring. Having an immature or suppressed immune system means more virus replicating.
Why Can’t we just Test for Mutated Viruses?
The mutation isn’t the same every time. There are two viral genes and the mutation pretty much always involves at least one of them but the mutation can occur in any number of places within either of these two genes. There are currently too many possible mutations to develop a meaningful test.
What Kind of Testing is Available?
At this time the diagnosis of FIP is clinical. This means that there is no positive or negative test; the doctor must look at the sum of several findings. These are some of the findings that are coupled with the physical examination and history findings to come up with a diagnosis of FIP.
Elevations in Total Protein, Alpha-2, and Gamma Globulins
Total serum protein is a simple value that can be checked in virtually every animal hospital in a matter of minutes. Cats with FIP commonly have high serum protein levels. There are many types of proteins in the blood. The type of protein that elevates in FIP is antibody levels of assorted types. If a blood panel is checked on a cat with FIP, serum protein is often divided into albumin and globulin amounts (adding these together provides the total protein level). When protein levels are broken down into these two groups, it will be the globulin level that is elevated. If the globulin level is further broken down, using a test called electrophoresis, it will be found that it is the gamma globulin levels that are elevated. The gamma globulins include antibodies and the FIP infection classically creates so much immune reaction that all antibody levels are elevated.
The Albumin to Globulin Ratio
FIP tends not only to elevate globulin levels but also to decrease albumin levels. Albumin is an important carrier protein in the blood and the body tends to conserve it at all costs. Albumin can be lost through glomerular disease or protein-losing enteropathy, or it can be underproduced by a failing liver. All these conditions can occur with FIP. FIP is usually associated with hyperproteinaemia (about 60%, although some studies have reported much lower prevalences than this) due to hyperglobulinaemia, usually with low or low-normal serum albumin; consequently the albumin: globulin ratio is low (less than 0.4 means FIP very likely, greater than 0.8 makes FIP very unlikely).
The FIP Titer
This test is often included on a blood panel and reflects a cat’s circulating antibody level against coronavirus. The problem is that coronavirus exposure is common in cats and is not particularly meaningful in diagnosing FIP. Furthermore, cats with fulminant FIP may not be producing FIP antibodies and have negative titers. The only time such a titer might be useful is if you are screening a healthy cat for coronavirus; in this event, a negative titer would indicate that the cat will not be shedding the virus and can be introduced into a coronavirus-free living situation. Many breeders strive for coronavirus-free catteries and such screening is important. The test does not help diagnose FIP in a sick cat, however.
Testing the Belly/Chest Fluids
FIP classically produces a clear but viscous yellow effusion, usually in the belly but possibly in the chest or both locations. The fluid typically has a total protein level greater than 3.5 mg/dl. Several efforts to find a diagnostic test that could be performed on this fluid have been made. So far we know that typically FIP fluid is high in lactate dehydrogenase, alpha-amylase, and adenosine deaminase. It is controversial whether or not a FIP antibody titer in the effusion fluid is of significance. Studies have been conflicting.
Rivalta’s Test
This is a test with which few veterinarians are familiar but it can help diagnose FIP. A test tube is filled with distilled water and one drop of 98% acetic acid is added. To this mixture, one drop of effusion is added. If the drop dissipates, the test is negative. If the drop retains its shape, the test is positive. A negative Rivalta test is 97% accurate in ruling out FIP. A positive test is 90% accurate in ruling in FIP in cats under 2 years of age.
PCR Testing
PCR testing is an extremely sensitive method for detecting DNA, in this case, coronavirus DNA. The advantage it has over traditional antibody titers is that it distinguishes active virus infection from past exposure. At least at this time, PCR testing cannot distinguish mutated FIP-causing virus from regular coronavirus.
Immunofluorescent Coronavirus Staining of the Effusion
In this test, the effusive fluid is tested immunologically for coronavirus using antibodies tagged with fluorescent dyes. In a study using a large number of cats, there were no false positives meaning that if this test is positive there is a 100% confirmation that the cat has FIP. Unfortunately, if the test is negative that does not mean the cat does not have FIP (only 57% of negatives did not have FIP).
Tissue Biopsy
Most FIP cats are too sick for surgery, though sometimes flushing away the belly effusion surgically provides a temporary rally of improvement. A tissue sample is the best method for confirming FIP as few conditions create pyogranulomas throughout the body but if a regular biopsy is equivocal, tissues can be stained for coronavirus and only in FIP will there be enough coronavirus within macrophages for positive staining. A positive tissue stain is 100% accurate in confirming FIP.
Is There No Effective Treatment?
There are two promising medications: GC376 (also called CL-Pro) and GS-441524 (marketed as remdesivir). It appears that GC376, a protease inhibitor, is on its way to commercial availability. In experimental trials, the medication was given by injection twice daily. Young kittens with newer infections can be cured after 12 weeks of treatment but cats with the dry form or with more long-standing infections may need indefinite treatment. This medication is not able to penetrate the natural blood/brain barrier and thus is not helpful if a neurologic form of FIP develops. Some cats experience sores at the injection sites and while these were felt to be minor, some scarring was permanent. The drug also prevented the development of adult teeth, leaving cats with their baby teeth still in place. Extractions of these teeth were frequently necessary. Out of 20 naturally infected cats and kittens, six were permanently cured and were able to discontinue the medication.
Results with GS-441524, a nucleoside analog, were better. Fewer side effects and relapses were readily dealt with by using higher doses. A few of the cats in the clinical trial died of unrelated conditions but the remaining 26 cats were able to achieve a cure. GS-441524 can cross the blood/brain barrier with higher doses and treat the neurologic version of the disease. The bad news (for cats) is that this medication is being developed to treat Covid-19, in addition to the human Ebola virus, and the feline market is a low priority.
Black market sources have emerged for both medications, especially those based in China. There is virtually no quality control for these substances and the conversion from powder to injectable, which is no small chemical feat, is done with unknown processes on the black market. Toxicity, contamination, and other issues are problematic and, while cat owners may be desperate, the use of black-market chemicals is discouraged.
Until at least one of these products becomes commercially available, there is no effective treatment for FIP and virtually 100% mortality. The goal of confirming FIP (as best as can be done) is to rule out other diseases that might be treatable. Currently, the best that can be offered with treatment is the possibility of temporary palliation of signs. It is important to realize that this is a progressive disease; one should become familiar with the criteria for euthanasia and emotionally prepare for this decision.
Are There Other Options?
Here are some treatments that are being or have been explored:
Immune suppression
FIP is a disease created by the cat’s immune system. Immunosuppressive drugs such as cyclophosphamide have been used to slow the progression of FIP.
Improved circulation
A medication called pentoxifylline improves red blood cell flexibility to allow better circulation through organs damaged by pyogranulomas. This is not felt to be a particularly effective treatment but it is not likely to hurt and might confer some better tissue oxygenation.
Removing the effusion
Suctioning the effusion will ease the difficulty breathing of a cat who has fluid in his chest, but even removing the effusion from the belly helps remove a large source of inflammation. Some cats have temporary improvement with the fluid removed.
Antiviral drugs
Ribavarin was tested and not found to be helpful. Interferon alpha was tested and not found to be helpful when given as an injection and made the infection worse when given orally. Feline interferon-gamma was investigated as another possible therapeutic agent but was not found to add any benefit.
Polyprenyl imunostimulant
This immunostimulant works by improving the number of helper T lymphocytes and improving the patient's immune response against the coronavirus. This medication is labeled for feline herpes virus infection but has also shown success in treating the dry form of FIP (but not the wet form). The investigation is ongoing.
When a Cat Dies of FIP, What is the Infection Risk to the Remaining Cat?
You can bet that the roommate has already been infected with the coronavirus. If there are only one or two surviving cats, the chances are that in time the virus will completely clear and they will stop getting reinfected. Surviving cats are felt not to have any higher risk over the general population for developing FIP from their coronavirus, though a littermate of the FIP cat might have a slightly higher incidence due to predisposing genetic factors.
When is it Safe to get Another Cat after one Dies of FIP?
Since this is not a contagious disease, one can argue that you do not need to wait before getting another cat. If you want to see that there is no remaining coronavirus around the house leftover from the deceased cat, a three-month period has been advocated. If there are surviving cats, you can periodically check FIP titers and wait for them to go negative before adding another cat if you wish to avoid passing around the coronavirus further. The new cat can also be screened for a FIP titer. When you consider that only 5% of cats in multi-cat homes get FIP despite the incidence of exposure to coronavirus being as high as 80% in some studies, this may not be necessary.
Isn’t there a Vaccination?
Developing a vaccination has historically been fraught with difficulty simply because it is the immune response against the virus that causes the disease. How does one make a vaccine without creating the same immune response against the virus? Only one FIP vaccine is on the market, and it uses a temperature-sensitive mutant coronavirus. This virus is inoculated into the cat’s nose. The virus is incapable of spreading beyond the nose and throat because it cannot survive at body temperature. In the nose and throat, however, it generates a localized immune response that prevents a coronavirus from effectively entering the body. The effectiveness of this vaccine has been questionable and remains controversial. The vaccine is given to cats over age four months of age and is thus not helpful in the chief situation where a vaccine could do the best: the breeding cattery. Because most cats are not at risk for FIP infection, and those that are at risk are too young for the vaccine, most veterinary teaching hospitals do not stock this vaccine.
The ideal candidate for vaccination would be an uninfected cat going to a cattery where litter box sharing is likely. This would seem to be an unusual situation but it might come up in these circumstances:
- A feral cat is moved into an indoor or shelter colony. (It is not unusual for cats infected with the feline immunodeficiency virus [FIV] from feral colonies to be removed from the colony and put in a sanctuary for FIV+ cats).
- A cat from a single-cat home is released to a rescue group and goes to a foster home where there are already a large number of other cats.
- A cat moves from a single-cat home to live in a multi-cat home.
Is Infection Limited to Cats?
Yes. Dogs and humans cannot get sick from feline coronavirus. The feline enteric coronavirus is not involved in SARS (severe acute respiratory syndrome) nor Covid-19, although both forms of SARS are caused by coronaviruses.
The information in this summary was largely drawn from K. Hartmann. Feline Infectious Peritonitis. Veterinary Clinics of North America Jan 2005; 39-79.
For General Information
For a Good FAQ:
Cornell School of Veterinary Medicine
On-going Research:
SOCK FIP
FIP is a serious disease with near 100% mortality, no good test, no good treatment, and no good vaccine. If your cat is a FIP suspect, we know how painful the lack of knowledge can be. We hope this information can provide facts and understanding during this difficult time.