Feline Infectious Peritonitis (FIP)

Imagine a disease that is infectious yet not contagious, has 100% mortality, virtually no diagnostic test to confirm it, and no effective treatment. When feline infectious peritonitis (FIP) becomes a possibility for a pet cat, questions abound yet not nearly enough answers.

What is FIP?

Feline infectious peritonitis is a syndrome that results from wide-spread 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. The “wet” form of FIP includes the thick, yellow fluid as noted. The “dry” form is more insidious, leading to death over a much longer period (often years). Both forms are felt to have 100% mortality.

Is FIP Contagious?

Very simply, the answer is no.

How Can an Infectious Disease not be Contagious?

Feline infectious peritonitis is a reaction to infection with the feline coronavirus. Most cats who become infected with the feline enteric coronavirus (often simply called feline coronavirus) essentially get the flu and never develop anything that can in any way be described as serious. Some cats, however, react with this devastating syndrome.

What do we Know about the Feline Enteric Coronavirus?

Some basics about this virus are:

  • It is common wherever cats are housed in groups and it is readily transmitted between cats.
  • Transmission is typically by contact with infected feces. This means that the litter box is the usual place where infection takes place. This infection is unusual in cats that free-roam outdoors (no litter box) or who live in homes where there is only one cat. The virus enters the new host’s body via the nose and mouth.
  • An active infection lasts several weeks to a few months. Virus is shed in the infected cat’s stool during this period. If the cat is reinfected, 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 virus.
  • Households with fewer than 5 cats eventually spontaneously clear of coronavirus. Households with more than 5 cats virtually never clear of coronavirus.
  • Most household disinfectants readily kill coronavirus immediately. Room temperature kills coronavirus within 48 hours. Carpeting is protective to the virus and the virus is able to survive in carpeting for at least 7 weeks.
  • 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.
  • The enteric coronavirus attacks intestinal cells and creates gastrointestinal (GI) upset. As long as the infection is confined to the GI tract, there will be no FIP.
  • The process of immunological defeat of the virus involves a cell called a macrophage. The macrophage consumes infected material, packaging it in special 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 in an attempt to kill the virus but ends up producing heaps of ineffective macrophages and immunologic proteins which make up a special immunologic tissue called a pyogranuloma. FIP is basically the infiltration of normal organs with pyogranulomas.
  • The mutation to a form of virus that can cause FIP is more likely to occur in a cat with an immune-compromise. Most cats with FIP are under 1 year of age (their immaturity being their immune-compromise). Crowding is also an important source of immune-compromise.

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 non-mutated virus.

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 was 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 infection has happened. Whether or not this mutation occurs seems to relate more to the cat’s immune status than any factor in the virus. The more virus there is replicating, the greater the chance of mutation occurring. Having an immature or suppressed immune system means more virus replicating.

Why Can’t we just Test for Mutated Virus?

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. A clinical diagnosis means that there is no positive or negative test; the doctor must look at the sum of several findings. Some of the findings coupled with the physical examination and history findings to come up with a diagnosis of FIP are:

• Elevations in Total Protein 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. Now, there are many types of proteins in the blood. The type that elevates in FIP is basically 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 it also tends to decrease albumin levels. Albumin is an important carrier protein in the blood and one’s body tends to conserve it at all costs. Albumin can be lost through glomerular disease, protein-losing enteropathy, or it can be under produced by a failing liver. All these conditions can occur with FIP. If the albumin to globulin level is less than 0.8, there is a 92% statistical chance that the cat has FIP. If the ratio is greater than 0.8, there is a 61% chance the cat does not have FIP.

• The FIP Titer

This test is often included on a feline blood panel and reflects a cat’s circulating antibody level against coronavirus. The problem is that exposure to coronavirus is common in cats and is not particularly meaningful in diagnosing FIP. Further, 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 one is screening a healthy cat for coronavirus; in this event a negative titer would indicate that the cat will not be shedding 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 is not helpful in diagnosing 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 in both locations. The fluid typically has a total protein level greater than 3.5 mg/dl. Several efforts have been made to find a diagnostic test that could be performed on this fluid. So far we know that “typically” FIP fluid is high in lactate dehydrogenase, alpha-amylase, and adenosine demaminase. It is controversial whether or not an 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 be helpful in the diagnosis of 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’s test is 97% accurate in ruling out FIP. A positive test is 86% accurate in ruling in FIP.

• 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.

There is a new test currently only performed at Auburn University that uses PCR technology to detect messenger RNA (produced by patient cells infected with coronavirus DNA) in the patient's blood. The theory is that the benign coronavirus cannot replicate in blood cells (only in intestinal cells) so if there is viral messenger RNA in the bloodstream, it must be from the mutated virus. The supposition that benign coronavirus messenger RNA cannot be found in the bloodstream has been challenged, however. While this may come down to a matter of how much messenger RNA can be detected in which situations, this test is very new and is still controversial.

• Immunofluorescent Coronavirus Staining of the Effusion

In this test the effusive fluid is tested immunologically for presence of 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 there are few conditions that create pyogranulomas throughout the body, but if regular biopsy is equivocal, tissues can be stained for the presence of 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 Really no Effective Treatment?

There really is no effective treatment for FIP and it has virtually 100% mortality (death). The goal of confirming FIP (as best as can be done) is to rule out other diseases that might be treatable. Currently the best we can offer with treatment is the possibility of temporary palliation of signs. It is important to realize that since this is a progressive disease one should become familiar with criteria for euthanasia and emotionally prepare for this decision.

Isn’t there at Least Experimental Treatment?

There is virtually always experimental treatment. Here are some treatments that are being explored or which have been explored:

• Immune suppression

FIP is a disease created by the cat’s own immune system. Immunosuppressive drugs such as prednisone and cyclophosphamide have been used to slow the progression of FIP.

• Removing the effusion

Suctioning of the effusion will ease the difficult breathing of a cat with fluid in its chest, but even removing the effusion from the belly helps remove a large source of inflammation. Some cats experience a 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 actually made infection worse when given orally. Feline interferon gamma is being investigated.

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 one does not need to wait before getting another cat. If one wants to see that there is no remaining coronavirus around the house leftover from the deceased cat, a 3-month period has been advocated. If there are surviving cats, one can periodically check FIP titers and wait for them to become negative before adding another cat if one wishes to avoid further passing of coronavirus. The new cat can also be screened for an FIP titer. When one considers that only 5% of cats in multi-cat homes get FIP even though in some studies the incidence of exposure to coronavirus is as high as 80%, this wait 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? Pfizer has developed the only FIP vaccine on the market by using a temperature-sensitive mutant coronavirus. This virus is innoculated 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 4 months of age and is thus not helpful in the chief situation where a vaccine could do the most good: the breeding cattery. Most veterinary teaching hospitals do not stock this vaccine because most cats are not at risk for FIP infection and those that are at risk are at risk at an age too young for the 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 FIV+ cats 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 goes to a foster home where there are already a 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 coronavirus is not involved in SARS (severe acute respiratory syndrome) although SARS is caused by a coronavirus.

 For General Information

A Good Starting Point

http://www.newmanveterinary.com/fip.html

 

 

Feline infectious peritonitis is a diagnosis cat owners know and fear. It is both heartbreaking and frustrating – it strikes the young, it is not treatable and is inevitably fatal, it is challenging to diagnose, and even more difficult to control. It’s a complex disease that is still not completely understood. So what do we know about FIP?

We know that feline coronavirus infection is required for FIP. This virus is a common infectious agent, especially in multi-cat households and catteries. It is shed from infected cats in the feces, can persist in the environment for several days, and infects other cats via inhalation or ingestion. In the majority of infected cats, it causes little or no problem. This becomes part of the challenge in diagnosing FIP: detecting the virus in samples (blood, feces, tissue) from a cat, or finding even high levels of antibodies to the virus in the cat’s blood (i.e. serology) doesn’t offer much information. In fact, it is quite common for cats to be virus positive, even in blood, and to have high levels of antibody to the virus. It doesn’t mean the cat has FIP, will develop FIP, or is protected against FIP.

We know that the majority of cats, even kittens, infected with feline coronavirus (FCoV) do not develop FIP. Most cats will clear the infection, and have no evidence of disease. Some cats remain chronically infected, shedding the virus in feces for months or longer; but even in these cases, it often has little effect on the cat. In a small percentage of infected cats, FIP develops.

Virus factors are important in FIP development. The normal target for FCoV is the intestines. In FIP, the virus is believed to mutate, or change in such a way that it then infects a type of white blood cell in the blood called monocytes and a type in the tissue called macrophages. In these cells, it replicates efficiently and eventually destroys the cell. It’s unknown what changes in the virus to allow this alteration in target from intestines to cells of the immune system. Because of this, there is no test that can distinguish the harmless virus from the one causing FIP – there is NO FIP-specific test. Still, in cases where this type of virus change occurs, most cats will be able to eliminate or control the virus before any disease develops.

For FIP to develop, other things have to happen. The disease itself is due not so much to the virus itself, but to the cat’s immune response to the virus. In those cats who develop FIP, antibodies to the virus are produced at high levels. But unlike cats who do not develop the disease, affected cats do NOT mount an effective antiviral response. An effective response requires more than antibodies, and for reasons still unknown some cats are not able to do this. The antibodies they do produce bind the virus as well as virus-infected cells, and cause significant damage not only to the virus and virus-infected cells but also to innocent bystanders nearby – uninfected cells that get “caught in the crossfire” of the immune response. Because the virus is not effectively eliminated, virus remains, the immune response continues, and the tissue damage snowballs. Eventually, the cumulative damage leads to organ failure and death.

So the disease itself is triggered by the virus, but is mediated by the immune response of the cat. The tissue damage occurs primarily in and around blood vessels. It may be widespread, affecting many blood vessels, leading to “leakiness” of the vessels themselves. This is the wet form of FIP, where fluid accumulates in the abdomen, chest, or both. In this form, the onset is relatively rapid, and the disease course short. Little can be done to help these animals. In other cases, the tissue damage is more restricted, occurring in single or only a couple of different tissues, such as the eye, kidney, liver, intestines, lung or nervous system. In these cases, referred to as the dry form (referring to the lack of fluid leakage), the onset is more insidious, and the disease course is longer. The clinical signs simply reflect which tissue is affected – e.g. evidence of eye infection, kidney failure, or diarrhea. Sometimes the clinical signs are vague – the so-called “ADR” cat – “ain’t doing right.” They exhibit weight loss, depression, decreased appetite, and lethargy. These animals can sometimes respond to symptomatic therapy for a time, but the disease is ultimately fatal in this form as well.

So why can’t some cats mount an effective antiviral response, allowing virus to persist, and leading to this fatal disease? The short answer is we don’t know. Much research is being done to decipher the reasons behind FIP development. We do know that predisposition to FIP development can be inherited, so there is likely a genetic component to disease development. This predisposition can sometimes be observed along familial lines, like a shared sire. What is behind this genetic predisposition also remains unknown. But whatever the reason, in the majority of FIP cases, it takes a combination of the right virus and the right cat. This is likely the reason behind the relative low incidence of FIP, though FCoV infection is common.

To make matters worse, because we can’t tell the harmless virus from the deadly virus and we can’t identify the factors that lead to FIP development, and because the signs and symptoms are often vague, diagnosis can be very difficult. In most cases it takes a combination of things to reach a diagnosis of FIP, including ruling out other diseases. This combination includes characteristics of the cat (usually young purebred), history (from a multi-cat setting, perhaps history of a stressful event, like surgery, boarding, or adoption from a shelter), and symptoms including decreased appetite, weight loss, fever that may wax and wane, and lethargy. For the wet form, the fluid in the abdomen or chest is an important clue, and analysis of this fluid can be helpful. But for the dry form, the specific tissue(s) that are involved may not be obvious. Physical exam may reveal enlarged abdominal lymph nodes, kidney abnormalities, eye infection, or neurologic disease, depending on which tissue(s) is/are involved. Or it just may reveal a cat who doesn’t feel well.

The veterinarian will have to do other tests to help make the diagnosis of FIP. These will include blood work at a minimum, as well as other disease-specific tests to rule out other diseases. But remember that there is NO single test that can diagnose FIP – no way to distinguish the harmless virus from the deadly one, no specific antibody level that means the cat has FIP, no one test that can confirm FIP. It takes analysis of various things – analysis of blood cells, organ function, fluid in the abdomen/chest, urine, even tissue samples from biopsy – to confirm the diagnosis of FIP.

Historically, treatment of FIP has involved suppression of the immune responses, since the lesions are caused by the cat’s ineffective immune response. But for obvious reasons, immunosuppression to treat a disease involving a virus infection will not be curative. Research is ongoing to develop more appropriate therapy to promote an effective immune response, one that can successfully clear the virus without causing significant tissue damage. Hopefully, in the future, an effective treatment will be found.

Currently, control or prevention of FIP has two main goals – prevention of FCoV infection, and breeding of more resistant cats. The former is quite daunting, if not impossible, in most multi cat settings – virus infection is common, most infected cats show no signs, and prevention of exposure is extremely difficult. There is a vaccine against coronavirus, but its use is not widely recommended. While it can offer some protection to cats who have never been exposed to the virus, in situations where FIP is a significant problem (i.e. in those populations in which one would need effective protection), kittens are usually exposed at a very young age before vaccination is begun. Thus, vaccination at 16 weeks of age, as the manufacturer directs, is too late to do much good. However, vaccinating a seronegative cat before introduction into a seropositive population may be helpful.

Breeding of resistant cats is also challenging since we don’t know what specific characteristics predispose a cat to FIP development. At most, if incidence of FIP occurrence in a breeding cattery increases, examination of breeding records of affected cats/kittens may reveal a common link and guide management decisions. But there is never a reason to euthanize a healthy cat simply because it has evidence of coronavirus infection nor because it has sired or borne a kitten that develops FIP.

For cat lovers and veterinarians alike, FIP remains a frustrating and heartbreaking disease. Advances in understanding the virus and the disease will hopefully lead to improved diagnostics, treatment, and prevention.

Blog Category: