Feline infectious peritonitis (Proceedings)

Feline infectious peritonitis (FIP) is feared by people who breed cats. It is also frustrating to the veterinarian because of the difficulties in making a definitive diagnosis. The gaps in the information needed for advising the owners about prevention are also frustrating. Our understanding of this disease is still incomplete but considerable information has emerged in the last few years.

The definitive diagnosis of the "dry form" of FIP can be difficult because even a complete necropsy may produce a vague report of "compatible with FIP." A clinical history of a cat under a year of age with lethargy and a persistent fever unresponsive to antibiotic treatment suggest FIP. Sparkes studied a number of cats with FIP as well as control cats with other diseases to identify laboratory findings that are supportive of FIP. He found that cats with compatible signs and a combination of lymphopenia, hyperglobulinemia and FIP titers above 1:160 had a positive predictive value (PPV) of 89% while cats that had none of these changes had a negative predictive value (NPV) of 98.8%. The only definitive way to establish a diagnosis is from histopathology of affected organs such as liver, kidney or omentum. In equivocal cases, immunostaining for coronavirus of tissues with granulomas will confirm the diagnosis but there may be only small amounts of virus even in cats with large granulomas.

The "wet form" is somewhat easier to diagnose from the typical pleural or peritoneal effusion. Effusions with total protein values of greater than 3.5 g/dl in which globulins make up greater than 50% of the protein have a PPV of 94% and a NPV of 100%. The diagnosis can be confirmed by immunostaining of macrophages in the effusion for coronavirus.

Polymerase chain reaction (PCR) techniques have emerged as a tool to identify the presence of coronavirus in the plasma or tissues of cats suspected of having FIP. The PCR technique was an especially worthy advance to study feline coronaviruses because standard virus isolation techniques in tissue culture do not routinely recover coronaviruses. At this time, I don't know of any studies that have identified the genetic difference between nonpathogenic feline coronaviruses that cause mild diarrhea and highly lethal coronaviruses that cause FIP. The primers currently used for PCR identify the feline coronavirus group. When the genetic differences between the virulent and avirulent viruses are known, then reliable primers can be made to separate the biotypes of feline coronavirus. The expression of the 7b protein in pathogenic coronaviruses has been proposed as a method of separating pathogenic and nonpathogenic viruses. A commercially available test is available to identify antibodies to the 7b protein. No convincing data has been presented by the company that gives the sensitivity and specificity of the assay. Dr. Kennedy at UT has identified 7b antibodies in 5 cats with confirmed FIP but has also found antibodies in 2 healthy cats.

The detection by PCR of coronavirus in the cat is important information because cats not infected with coronavirus don't get FIP. Coronavirus is endemic in multiple cat households and catteries. Surveys done in California and in Switzerland have not identified active catteries free of coronavirus. Li and Scott found coronavirus by PCR in spleen, liver and kidneys of 8 of 9 cats with FIP but they also found coronavirus in 61% of cats that died of diseases other than FIP. Until specific primers are developed, PCR remains a research tool to study the transmission of coronavirus in catteries.

Previously, the presence of coronavirus systemically was considered an indication of FIP because the avirulent virus was believed to be confined to the gut. With PCR techniques coronavirus was found in plasma of 37% of cats in a breeding colony. The cats remained healthy for 8 months after testing.

When a diagnosis of FIP is made, what should we recommend doing with the other cats in the household? To make valid recommendations we need to better understand coronavirus transmission between cats and the events that lead to FIP. Coronavirus is enzootic in almost all households where there are 10 or more cats. Yet, epidemics of FIP are uncommon. Addie showed that kittens from households infected with coronavirus were no more likely to develop FIP if there had been a death from FIP in the household. This is not consistent with an infectious disease that progresses rapidly through the cat population. This is more consistent with a widely distributed virus that in certain cats mutates to a virulent form and causes disease if the cat is not able to contain the infection.

The theory of mutation of a highly contagious, nonpathogenic enteric replicating coronavirus was originally proposed by Pederson and current studies strongly support the mutation theory. Coronaviruses are RNA viruses that lack proof reading capability therefore they are very prone to mutations. Cats that have prolonged and high levels of virus replication are by chance more likely to develop a pathogenic mutation. Young kittens that have not previously been exposed to coronavirus are most likely to produce large amounts of virus until an immune response occurs. When a pathogenic mutation occurs, the pathogenic mutation may cause the death of the cat. It appears that each case of FIP is due to a unique mutation that occurs in that cat and that pathogenic virus usually dies with the cat.

Not all cats that have a pathogenic mutation will develop FIP. There are cats that appear to be genetically more susceptible to development of disease. If the cats mounts an adequate cell mediated immune response, it may clear the infection. This would explain the increase incidence of FIP in cats that are immunosuppressed from concurrent infection with feline leukemia virus. Stress may also increase the susceptibility to FIP by suppression of the immune system and by allowing more intensive production of coronavirus in the gut. After entering a shelter, the amount of virus shed by a cat will increase by 2 to 3 logs. This increase virus production naturally increased the likelihood of development of a pathogenic mutation.

Fecal-oral transmission is the usually route of cat to cat transmission of coronavirus. Large amounts of the nonvirulent coronavirus is shed in the stool, but when a pathogenic virus develops it develops an ability to grow in macrophages. It is believed that the adaptation to macrophages greatly decreases the ability of the virus to replicate in the gut. Forty to 60% of cats with FIP excrete coronavirus in the stool but the excreted virus appears to be mainly the nonvirulent enteric coronavirus. The occasional cat with FIP that excretes virulent corona virus, possibly in the urine, may be the cause for the uncommon epidemics of FIP that produce mortality rates above 10%.

Kittens born into catteries with chronic corona virus infection were shown by Addie to have mortality rates of 4.8% over a 36 month study. The only way to prevent FIP was to prevent infection with coronavirus. Addie showed that kittens kept with their queen away from other cats had half the incidence of FIP as kittens roaming freely in the household. Kittens kept isolated with their queens and weaned early at 4 to 6 weeks of age did not develop coronavirus infection or FIP. While very effective, the strict isolation is difficult because coronavirus is highly contagious and can be spread by fomites. Some breeders believe that early weaning and removal of kittens from their queens interferes with social development of the kittens. Other investigators have been unsuccessful in preventing coronavirus infection by early weaning and isolation of kittens. This was attributed to finding coronavirus in the stool of kittens as early as 2 weeks of age. This is consistent with our experience.

Using PCR techniques to identify cats shedding corona virus, Foley showed that cats shedding virus could not be identified by antibody titers. Young cats were more likely to excrete virus and to develop FIP. Some cats in the household were constant fecal virus shedders while other cats shed virus intermittently. All kittens born in the households became seropositive. The pattern of fecal virus shedding is consistent with infection, immune control of virus shedding, loss of immunity and reinfection with fecal virus shedding. Identification of cats that are frequent shedders may reduce the viral contamination in a cattery but is unlikely, as a sole control procedure, to eliminate corona virus infection. Cats that are constant shedders of virus are more likely to have high antibody titers. The intermittent shedders will have moderate to high antibody titers making identification of constant shedder cats difficult using antibody testing.

Vaccination could be very helpful in control of coronavirus in catteries in combination with isolation procedures. The currently available FIP vaccine has been shown to reduce incidence of disease but it does not seem to be effective in cats already infected with coronavirus. In our studies, all kittens in the cattery were shedding coronavirus long before the recommended 16 weeks of age vaccination date.

Owners should be advised that FIP is a sporadic disease and that development of disease in an coronavirus infected environment is a matter of luck. A breeder that has had a cat with FIP should not be ostracized by other breeders unless their catteries are free of coronavirus. Reduction of stress and reduction of the amount of virus transmission by providing ample numbers of litter pans and changing them often may help reduce viral load in the cattery.

FIP has long been considered a fatal disease. The only report of long term control is a non-placebo controlled study done by Dr. Ishida in Japan using glucocorticoids and recombinant feline interferon omega. This treatment produced 2 year remissions in 4 of 12 cats with FIP. In a placebo controlled, double blind study of 37 cats in Europe with mainly the effusive form FIP treated with steroids, amoxicillin/clavulanic acid and recombinant feline interferon omega; Ritz et al. showed no difference between the placebo group and the group treated with recombinant feline interferon. Median survival time for all cats was 9 days with the longest surviving cat living for 200 days. The cat that survived 200 days was in the placebo group. Feline interferon is not available in the United States. In a pilot study of cats with the dry form of FIP, we have had 2 cats treated with Polyprenyl Immunostimulant that are alive and well 2 1/2 years after diagnosis. No benefit was noted in cats with the wet form of FIP. Information about the Polyprenyl Immunostimulant study of cats with dry form FIP can be obtained at alegendr@utk.edu

References

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