An Interview with Dr. Pedersen about FIP

The following text originated in an interview with Dr. Niels C. Pedersen by Nancy Reeves , published in October 2008.

WHAT IS FELINE INFECTIOUS PERITONITIS?

FIP is caused by a feline coronavirus.Coronaviruses of various species exist in most types of animals and humans and usually cause acute respiratory or enteric disease.FIP is the cause of death of 1 in 100 to 1 in 300 cats in U.S.The incidence can be 5 or more times greater among young cats coming from catteries and shelters and is the major cause of abdominal fluid (ascites) and intraocular and neurologic inflammatory disease in cats under 3-5 years of age.FIP is virtually 100% fatal and there is no good prevention.The emotional toll of FIP is especially great, because it strikes suddenly weeks, months and even years after initial infection.Therefore, cat lovers usually experience this disease long after they have developed strong emotional bonds with their new pet.

HOW IS THE CORONAVIRUS SPREAD?

Coronviruses are ubiquitous among all cat populations and the principle one of cats is correctly referred to as feline enteric coronavirus (FECV).FECV is present in virtually all catteries with 6-8 or more cats and up to 40% or so of the kittens relinquished to shelters. The enteric virus in the cat population lives in the digestive tract and is shed in feces. Cats can shed the virus for 4-6 months or for a year or more in a continuous or intermittent fashion.Recurrent infections are also common.FECV is readily spread through litter and litter dust, and can be carried from place to place on people's bodies and clothing.Virus contaminated material is easily transferred to the paws and fur of susceptible cats and then ingested during grooming.Kittens are infected by other cats at about 9-10 weeks of age, although one report places it as early as 3 weeks.

HOW DOES THE CORONAVIRUS TURN INTO FIP?

FIP is caused by a mutation of FECV. Although the mutation of FECV to FIPV is common, it is fortunate that only a small percentage of cats exposed to this mutant virus will get FIP. FECV is undergoing continuous mutation and several genetic forms of the virus may co-exist in the same animal at the same time.Most of these mutations have very little effect on the behavior of the virus and merely serve to genetically reflect the region from which the virus originated.However, certain have a pronounced effect on the biologic behavior of the virusOne study indicated that 20% of the kittens infected with FECV will produce an FIP mutant.Of course, only a fraction of the mutants will go on to produce FIP, depending on host resistance factors (genetic or non-genetic).

This FECV to FIPV genetic change is referred to as the internal mutation theory.The internal mutation theory has two corollaries: 1) that each cat that develops FIP, even if it is a littermate, closely related or commonly housed, has a unique mutation, and 2) that horizontal (cat-to-cat) transmission of the FIPV mutant is uncommon. Researchers at UC Davis have reconfirmed corollary 1, and have confirmed corollary 2 in concept but not in fact.Reconfirmation for the internal mutation theory came from a recent outbreak in three kittens in a litter of Scottish Folds and in a half-sibling from a second litter.All four FIPVs had very similar yet genetically unique gene mutations. These mutations were not present in a fecal form of the virus that was being shed by a healthy contact cat.

WHAT IS THE HISTORY OF FIP?

FIP was first recognized as a specific clinical entity in the late 1950's.This timeline was based on decades of meticulous necropsy records kept by pathologists at the Angell Memorial Animal Hospital.There was a steady increase in the incidence of the disease in the 1960's onward, and it is currently one of the leading infectious causes of death among young cats from shelters and catteries.

The reason for the sudden emergence of FIP is not known, but there are at least two possible explanations. First, it is noteworthy that FIP appeared within a decade of the initial descriptions of transmissible gastroenteritis (TGE) of pigs in North America.The causative virus of FIP is closely related to TGEV of pigs and canine coronavirus (CCV), although they are still genetically distinguishable.However, mixtures between these three viruses are known to occur.At least one strain of canine coronavirus can induce mild enteritis in cats and enhance a subsequent infection with FIPV, indicating a special closeness to feline coronaviruses.Therefore, CCV may be a more likely parent of FECV in this scenario.Another related possibility is that the FIP mutation occurs only in a relatively new strain of FECV, and that this new strain only evolved in the 1950's.Coronaviruses such as FECV are continuously mutating as a result of the manner in which their genetic material (RNA) is replicated. Therefore, genetic change, either among themselves or through genetic mixing with closely related coronaviruses from other species, could have either allowed a coronavirus of another species to take up host in cats or to alter a strain that existed prior to the 1950s.

An alternative non-genetic explanation may involve changes in how cats were viewed as pets and their husbandry.There was a dramatic shift in the status, keeping, and breeding of cats as pets after WWII.The numbers of pet cats greatly increased, pure breeding and cattery rearing became increasingly popular, and more cats, and in particular kittens, found themselves in shelters. These large multiple cat indoor environments are known to favor feline enteric coronavirus (FECV) infection and FIP.Interestingly, feline leukemia virus (FeLV) infection also became rampant among indoor multiple cat households during this period, and FeLV infection was a significant enhancing factor for FIP until it was pushed back into nature as a result of testing, elimination/isolation, and eventual vaccination in the 1970s and 1980s.

WHICH CATS ARE SUSCEPTIBLE TO FIP?

FIP affects both pure- and random-bred cats. However, the disease usually starts in young kittens so it is closely linked with cat breeding and sheltering.The disease is also enhanced by improper husbandry, especially resulting from overcrowding (shelters, large multiple cat households).

We also know that genetic susceptibility may account for 50% or more of the risk of developing FIP in one pure breed that was studied.Although FIP occurs in all breeds, there is no doubt that certain bloodlines, and therefore certain matings, are more apt to produce kittens that eventually die from FIP.These genetic factors are most likely a result of the inbreeding that goes into breed development. Therefore, catteries are at the highest risk because they are subject to a high level of all three risk factors (kitten production, dense housing, genetic susceptibility).The likelihood that any given cattery will suffer at least one outbreak of FIP over a five year period is very high, and mortality in catteries can be several times higher than it is in the general population.

Shelters have the second highest risk of FIP, and the greatest incidence is among kittens adopted during periods of overcrowding and prolonged stays.Most shelter kittens are random bred, with many coming from the feral cat pool.Random bred kittens are more genetically diverse in general, so husbandry factors are more important in causing FIP in this population than genetic factors.Husbandry factors are greatly influenced by the seasonal influx of kittens.

WHY ARE YOUNG CATS AFFECTED BY FIP?

The age of the cat at the time of initial FECV exposure may play an important role in whether a cat dies from FIP.Kittens usually began shedding FECV at around 9-10 weeks of age, which places their actual exposure a few days to a week earlier.The immune system of the kitten is rapidly maturing during the period between 6-16 weeks of age.Therefore, the first exposure of most cats to FIP causing mutants occurs during a time period when their immune systems are still developing. This lack of development enhances the likelihood of a FIPV mutant to gain a strong foothold into the body.Just as there is an age susceptibility, there also appears to be an age resistance. FIP is seldom seen in cats over 3-5 years of age, and most cases occur before 16 months of age.

HOW DOES STRESS PLAY A ROLE IN FIP OCCURRENCES?

Anything that stresses cats can depress immunity and also increase the likelihood that FIPV will establish itself in the body.Stress may also allow an FIPV that is being successfully contained to become active. The effect is even more powerful if the stress occurs at or shortly after the time the cat is exposed to the virus.Stressors can include overcrowding, weaning, spaying or neutering, other infections, being placed in a new and strange household, adding new cats to a household, shipping cats to new owners or other catteries, or stresses of pregnancy, parturition and lactation.Disease caused by feline herpes virus and other common upper respiratory pathogens are good indicators of cattery or shelter stresses.

If a cattery or shelter is having a lot of problems with these upper respiratory infections, it is likely that they will also have problems with FIP (especially if the genetics are unfavorable as well).For instance, one shelter had a huge FIP problem in the kittens they were adopting out.It was kitten season and the facility was overcrowded with cats and they had to stay for longer periods awaiting adoption.There was also a lot of upper respiratory disease.After researchers at UC Davis recommended limiting their intake of cats, overcrowding was eliminated and cats were adopted after shorter stays.The FIP problem decreased as did the respiratory infections.

WHAT ARE THE SIGNS OF FIP?

Signs of FIP arise weeks, months, and in rare cases years after initial infection. During this quiescent stage, the cat may be asymptomatic or suffer from vague signs such as stunted growth or increased susceptibility to other common infections.Many believe that FIP can cause upper respiratory disease signs during its early stages; this is not technically correct, because upper respiratory disease is usually caused by herpesvirus, chlamydophilla, mycoplasma, etc., and not directly by FIPV.

With time, many cats win their battle with this infection, while others lose.However, "losing the battle" may occur over a very long period of time; only terminally, when the cat's defenses collapse, do the more characteristic signs of FIP develop. This capitulation to the virus explains why cats with FIP seldom recover, because a loss of immunity is extremely difficult to reverse.Although unappreciated in the past, we now know that cats in the terminal stages of FIP are often severely immunocompromised.This explains why common bacterial infections may complicate the disease picture in cats with FIP.

Cats who develop clinical cases of FIP may initially show nonspecific symptoms such as growth retardation, loss of appetite, depression, rough coat, weight loss, a fluctuating antibiotic resistant fever, and increased susceptibility to secondary infections (such as respiratory disease).More specific signs of FIP vary depending on the form of the disease (wet vs. dry) and the organs that are involved.

The most common form of the disease is referred to as "wet FIP."Wet FIP is caused by inflammation of the linings of the abdominal viscera, and less commonly of the thoracic organs. This inflammation exudes large volumes of a characteristic mucinous, yellow-tinged fluid (exudate).Therefore, the major clinical sign in the wet form of FIP is ascites and abdominal distension (abdominal involvement) or dypnea (thoracic involvement).

FIP can also take a more chronic form referred to as "dry FIP."Dry FIP, as the name implies, is not associated with fluid accumulations in the abdomen or chest, but rather with more localized masses in the kidneys, spleen, liver and terminal bowel, eyes, and the linings of the lungs and heart, and central nervous system.Uveitis (intraocular inflammation) can affect the eyes, making them look cloudy and changing the color of the iris.Inflammation can enter the brain and spinal chord and cause a spectrum of progressive neurologic abnormalities.FIP accounts for over one-half the cases of inflammatory intraocular and nervous system disease in cats under 3-5 years of age.

IS FIP CONTAGIOUS?

Cats with FIP do not appear to be very contagious to cats that they come in contact with.Although this has been based mainly on clinical observations, it has also been confirmed by laboratory studies.Contact transmission has not been observed in experimental settings.Furthermore, cat-to-cat transmission implies that every FIPV isolated from a group outbreak of FIP will be genetically identical. UC Davis researchers have yet to observe this.However, researchers now know that FIPV is present in the feces of some cats with FIP, so horizontal transmission is theoretically possible, and may explain the uncommon epizootics of FIP where a number of cats in the same environment develop FIP within a days or weeks of each other.

IS THERE A DEFINITIVE TEST FOR FIP?

There is no single definitive test for FIP at this time, however the diagnosis of FIP should be relatively simple given its affinity for younger cats, its strong tendency to involve catteries and shelters, the typical physical and historical findings, and numerous characteristic laboratory abnormalities.Nonetheless, it remains one of the most difficult of diagnoses for many veterinarians. The truth is that veterinarians have little trouble in placing FIP high, or at the top, of their diagnostic list, but have great difficulty, and even reluctance, in confirming their diagnosis.This is probably because FIP is viewed as a death sentence, and they are reluctant to confer such a sentence without certain proof.

Although a definitive test result would assist decision making, a certain diagnosis can be based on cumulative odds rather than a single, simple, definitive test result.A young cat from a cattery or shelter with chronic uveitis and/or neurologic signs, high serum proteins, hyperglobulinemia and hypoalbuminemia, fluctuating antibiotic unresponsive fever, leukocytosis with a lymphopenia, and an anemia of chronic disease can have no other disease than dry FIP based on odds alone.Likewise, the same cat with similar history and laboratory findings, but with yellow-tinged, mucinous, inflammatory ascites is highly unlikely to have any other disease than wet FIP.

In an attempt to reach the elusive definitive diagnosis, veterinarians rely on dozens of tests that claim to highly correlate with the disease or to be diagnostic.However, the only good definitive way to diagnose FIP is to identify the virus in macrophages within lesions or ascetic/pleural fluid by a procedure called immunohistochemistry. PCR would work equally well on diseased tissues or fluids, but many of the current tests are improperly designed and conducted and frequently yield misleading results.In some cases, the proper fluid or tissues cannot be obtained pre-mortem.A necropsy should be done by a qualified veterinary pathologist on any cat that requires a proper diagnosis.

HOW TO CARE FOR A CAT WITH FIP

There is currently no cure for FIP; therefore, the primary concern needs to be making the cat comfortable and deciding when to quit.Cortisone can help reduce inflammation and encourage appetite.Good nutrition, hydration and non-stressful environments are also important, but in almost all cases they serve only to prolong the inevitable. Therefore, we will encourage some owners to go with symptomatic treatment, but only if the animals are not suffering.Owners of cats with FIP should be wary of claims for alternative type therapies that are based on anecdotal evidence.

ARE THERE ANY TREATMENTS FOR FIP?

There have been reports that the feline interferon omega is effective in combating FIP.Davis researchers actually tested it against FIP years ago and it did not work.Fortunately, a double blind, placebo controlled study was recently reported from Europe on the use of interferon omega in treating FIP.Cats receiving this very expensive treatment fared no differently than placebo treated cats.

WHEN TO MAKE THE DECISION TO EUTHANIZE

This is a decision only the cat's owner can make, and it is a difficult one.It is not recommended to euthanize a cat, even with FIP, as long as it looks and acts fairly normal.Miracles do happen, but they can't happen unless they are provided time to happen.However, some owners choose to end suffering at an earlier stage, given the grave prognosis.

Many owners decide to put an animal down when it no longer takes pleasure in life.But cats can feign health to the last.There is a myth that if a cat is still purring it is still enjoying life.Research has shown, however, that cats purr even when in extreme pain, it is another way that they mask illness.

WHEN CAN YOU BRING IN A NEW CAT AFTER FIP?

If you have lost a cat to FIP, remove any cat related items that you cannot wash or disinfect, such as a scratching post or soft toys.Clean and disinfect everything else in the environment that you can.Time will take care of the rest, because viruses of this type are not long-lived in the environment.A couple of months are recommended, which is standard for most infectious diseases.

DOES THE FIP VACCINE WORK?

A vaccine has been developed and is available.However, it has to be used in kittens at least 16 weeks of age (most cats are already exposed to coronavirus at this age), it is not effective in cats already exposed to coronavirus (which is most cats), it is not effective against the common serotype of FIPV, and even when all factors are optimal, it has low efficacy.In short, it does not work in the environments where it is needed most (catteries and shelters) and is not justified in older pet cats where FIP is hardly seen. UC Davis researchers do not recommend its use.

WHAT ARE SOME WAYS TO HELP PREVENT FIP?

Avoid stress and overcrowding.Keep cats in small, separate groups.Consider isolating kittens from a mother cat at weaning to avoid exposure to the virus.Don't mix very young kittens with older kittens.If you can limit coronavirus exposure until 12-16 weeks of age, when the immune system is better developed, the likelihood of developing FIP may be lessened.Breeders should avoid matings between cats who have had close relatives that have died of FIP or who have produced kittens that developed FIP.

Also follow accepted protocols for vaccinations and practice good husbandry to limit other infections.Clean and disinfect cages and litter boxes regularly.The corona virus is easily killed by bleach and other disinfectants.

WHY IS THERE HOPE NOW FOR FIP BREAKTHROUGHS?

It is true that there is currently no cure, or totally effective prevention.But researchers understand the virus and the infection much better now.They have new tools that allow them to look at viruses at the molecular level. Any knowledge about the virus and how the host cat responds to it will have influence down the road.The Feline Genome has been sequenced, and with this important new feline DNA roadmapresearchers will be able to identify viral genes responsible for causing disease (which will facilitate antiviral drug development) and host genes that confer resistance/susceptibility (which will facilitate genetic control).

Understanding how the immune system affects both resistance and the form of FIP (wet vs. dry) will also be important.Immunity studies will focus on how to modify the immune system's reaction to the virus. Understanding how to block inflammation and the development of anti-viral drugs would be ways to fight FIP.There is no reason why these can't be developed.Drugs could be developed and used in FIP with some effect - like HIV/AIDS it could become a manageable disease

If the genetic basis for susceptibility can be identified, genetic testing would allow breeders to breed out the trait over several generations, while preserving valuable bloodlines. This is exactly what breeders are doing with many other genetic diseases, such as polycystic kidney disease in Persians and breeds with Persian blood.It potentially could also identify random bred cats that are at risk for the disease, allowing caretakers to reduce FIP deaths in shelters by limiting exposure to stressful environments or other factors.

HOW MUCH MONEY IS NEEDED FOR FIP RESEARCH AT UC DAVIS?

All funds given to SOCK FIP for the CCAH will go right into FIP research. Some of this research will be clinical in nature, and some bench top.$50,000 - 75,000 a year supports a single technician or graduate student, and the more such people the CCAH can engage in research the faster we will reach our goals.

The genetic testing will be expensive - the DNA chip arrays will cost $400 or more each just to purchase (once they are developed by commercial companies), read, and analyze.As demonstrated by SOCK FIP's predecessor, SOCK it to Leukemia, a great deal of money can be raised by ordinary people), and a lot can be accomplished with that money if it is concentrated in the hands of knowledgeable and capable researchers.

WHAT ABOUT OTHER UNIVERSITIES AND INSTITUTES THAT STUDY FIP?

Though SOCK FIP is trying to focus funding on U.C. Davis for greater impact, the scientific community is very collaborative and pedigree/disease information and DNA samples will be useful for meaningful collaborations.UC Davis researchers are also aware that other groups are raising money to study FIP, and this is also respected and accepted.

The goal of SOCK FIP and the UC Davis Center for Companion Animal Research is to solve FIP and in the end it really does not matter how it is accomplished or who does it.Scientific competition is always good.A world full of researchers have studied this disease for over 40 years, and although we know a lot more about it, we still do not have effective ways to totally prevent or cure this disease.Hopefully, this worldwide research effort will finally bear the needed fruit.Researchers at UC Davis and the CCAH can only do the best as their part.