(Photocredit: morguefile.com)

WHAT IS FIP?

Feline Infectious Peritonitis is a syndrome that results from wide-spread infiltration of the body’s organs with inflammatory tissues called “pyogranulomas.” The resulting global inflammation leads to the failure of the infiltrated organs, fevers unresponsive to antibiotics, and often the accumulation of thick yellow fluid in the belly or chest. The “wet” form of FIP, includes the effusion of thick, yellow fluid as noted. The “dry” form is more insidious, leading to death over a much longer period (potentially years, but more 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.

cat with distended abdomen from fluid accumulation
(original graphic by marvistavet.com)

SO 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 a contagious virus but most cats that get infected just get temporary flu-like symptoms (fever, diarrhea, malaise). Feline Infectious Peritonitis is a very 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 about the virus. The virus is contagious but a cat cannot transmit FIP to another cat.

(Photocredit: Morguefile.com)

WHAT DO WE KNOW ABOUT THE FELINE ENTERIC CORONAVIRUS?

Here are some basics about this virus:

Electron Micrograph of a Coronavirus
showing the characteristic halo-like
structures for which it is named.
(Photocredit: CDC Public Heath Image Library)

• 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.

(original graphic by marvistavet.com)

• 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 GI upset. As the long as the infection is confined to the GI tract, there will be no FIP.

(original graphic by marvistavet.com)

 
A macrophage is called to areas of inflammation to consume
and destroy cells and organisms that do not belong. The invader's
parts are displayed on the macrophage's outer surface to
facilitate stimulation of antibody producing lymphocytes.
(Photocredit: Public Domain Graphic from United States Department of Health and Human Services)

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 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 age 1 year (their immaturity being 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.

• Genetics
  
  
• Early weaning
  
  
• Overcrowding
  
  
• Age at the time of coronavirus infection
  
  
• Surgery stress (usually spay/neuter)
  
  
• Sharing litter box with other cats

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” different from ordinary enteric coronavirus. 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 occurred. Actually, 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 mutation occur in any given infection caes seems 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.

(original graphic by marvistavet.com)

WHY CAN’T WE JUST TEST FOR MUTATED VIRUS?

The mutation isn’t the same every time. There are two relevant 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.

• Elevations in Total Protein, Alpha-2 and/or 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 very high serum protein levels. That said, there are many types of proteins in the blood. 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 special test called “electrophoresis,” it will be found that it is the “gamma globulin” and "alpha-2 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.

(Photocredit: Morguefile.com)

• 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 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 alpha-1 glycoprotein. The presence of such proteins provides evidence of the inflammatory nature of the fluid and would be evidence pointing towards FIP (though any other inflammatory fluid would yield similar results). 
• “Rivalta’s Test”
  This is a test with which few veterinarians are familiar but it can be very 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 90% accurate in ruling in FIP in cats under age 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.

There are two very 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 experience cure 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 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 medication.

(Photocredit: Morguefile.com)

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.

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? Zoetis (formerly Pfizer Animal Health) has developed the only FIP vaccine on the market by using 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 in controversy. The vaccine is given to cats over age 4 months of age and is thus not helpful in the chief situation where a vaccine could do the most good: the breeding cattery. Because most cats are not at risk for FIP infection and those that are, are at risk at an age too young for the vaccine, most veterinary teaching hospitals do not stock this vaccine.