Feline Infectious Peritonitis – FIP

One of the most poorly understood feline viruses is the feline coronavirus, the virus responsible for feline infectious peritonitis (FIP). It is no exaggeration to say that this is one of the most feared diseases amongst shelters, boarding catteries and breeders. Many facilities that remain in operation for several years will have a brush with FIP. Despite the fact that this disease is a shared experience in the cat fancy, affected catteries are wrongly feared and ostracized. People need to make efforts to understand this disease and how to control it.

Feline coronavirus behaves differently from other feline viruses in important ways:
a) Systemic antibodies to coronavirus have no protective function for the cat and may play a role in the disease itself
b) Antibody titres have limited usefulness for diagnosis of FIP or predicting which cats are at risk of developing FIP
c) A vaccine is available in some countries, but there is no consensus on its efficacy or safety

Terminology
FIP is the term for clinical disease associated with feline coronavirus infection. The common benign form of feline coronavirus is referred to as FECV (feline enteric coronavirus). When FECV has mutated into a disease-causing form, it is then referred to as FIPV (feline infectious peritonitis virus). Feline corona viruses in general are referred to as FCoV

FECV and Mutation to FIP Virus
FECV is a very common, highly infectious feline virus. The majority of cats with FECV (about 95% or more) remain healthy. But in a small number of cases, FECV infection is the first step in a chain of events leading to FIP. This happens because coronaviruses are made of large numbers of nucleotides, the basic unit of genetic material, and they are very prone to mutations. As a virus reproduces itself, errors are made in copying these nucleotides. While most of these errors are harmless, some will have the effect of giving FECV the ability to cause disease. These mutant FECV strains are called FIPV.

Recent research has shown that mutant FECVs arise within an individual cat. We now know that the vast majority of cats do not “catch” FIP, but they develop it themselves from their own mutant FECV. Non-pathogenic FECV lives within the cells of the intestinal tract and may be shed into the faeces and spread to other cats. But FIPV (the mutant form of FECV) has developed the ability to live and replicate within cells of the immune system called macrophages. FIPV are able to spread throughout the cat’s body, and are no longer localized in the intestinal tract and so are rarely shed into faeces. Transmission of FIP from cat to cat is considered to be rare. Cats who are ill with FIP are unlikely to be a risk to other cats and thus do not need to be isolated. It has been estimated that in multi-cat households where FECV has been introduced, 80-95% of all the cats will be infected. In the general cat population, infection rates may reach 30-40%. Catteries are especially likely to be FECV positive. However, the number of cases of FIP is quite low in comparison to the number of cats infected with FECV. Generally, most catteries experience far less than 10% losses to FIP over the years. Uncommonly, an apparent epidemic of FIP is associated with mortality rates of over 10% in a short period of time. Usually, losses are sporadic and unpredictable. The peak ages for losses to FIP are from 6 months to 2 years old. Age-associated immunity to FIP appears to be possible. Transmission of FIP from a queen to her unborn kittens has not been shown to occur.

Risk Factors for FIP 
What are the factors that predispose a small percentage of cats with FECV to the development of FIP? Three key risk factors have been identified: genetic susceptibility, the presence of chronic FECV shedders in the cattery, and cat-dense environments that favour the spread of FECV.

Research has shown that the heritability of susceptibility to FIP may be very high (about 50%). It is likely a polygenetic trait rather than a simple dominant or recessive mode of inheritance. Inbreeding, by itself, is not a risk factor. Selecting for overall disease resistance is a helpful tool for breeders. The likely defect in immunity to FIP is in cell-mediated immunity. Therefore cats that are susceptible to FIP are also likely susceptible to some other infections as well, especially fungal and viral infections. This finding gives breeders the ability to achieve success in reducing the risk of FIP by using pedigree analysis to select breeding cats from family backgrounds that have strong resistance to FIP and other infectious diseases.

FECV Shedding Patterns 
There are two main patterns that occur with FECV infection. Most cats (70%) will become infected and recover, but will not be immune. They are susceptible to reinfection the next time they contact the virus. A small number of cats (15%) become infected but do not recover. They become persistent shedders of FECV in the cattery and are the source of infection for the other cats although they may never become ill themselves. Therefore, the key to eliminating FECV (and thus the risk of FIP) in a cattery would be the identification and removal of chronic shedders. The coronavirus antibody titre cannot reliably be used to determine which cats are chronic shedders. The most effective and practical tool is PCR analysis of faeces for the presence of FECV over a period of several weeks.

Control Measures 
In addition to selecting disease-resistant breeding stock, breeders, shelters and boarding catteries can initiate husbandry practices that discourage the spread of FECV and development of FIP. Cat-dense environments favour the transmission of the highly contagious FECV. The ideal way to house cats in catteries is individually. However, since this is not always possible, cats may be kept in stable groups of no more than three or four. Kittens should remain in groups of similar ages and not be mixed with adults in the cattery. Any measures that reduce environmental and social stress in the cattery population will have a beneficial effect.

FECV is spread primarily by the faecal-oral route. The virus can persist in the environment in dried faeces on cat litter for three to seven weeks, so scrupulous cleaning of cages and litter trays is important to reduce the amount of virus in the environment. Fortunately, FECV is susceptible to most common disinfectants and detergents. It is important to have adequate numbers of litter trays. Litter trays should be kept away from food bowls and spilled litter should be regularly cleaned up.

Clinical Signs of FIP
There are two forms of FIP. The effusive (wet) form is characterized by accumulation of fluid in the chest or abdomen. This fluid is high in protein content and is often a yellow colour. The non-effusive (dry) form of FIP is characterized by inflammatory lesions called pyogranulomas that can be found in almost any organ of the body, including the nervous system. Signs of illness common to both effusive and non-effusive forms of FIP include loss of appetite, weight loss, lethargy, and a fluctuating fever that is not responsive to antibiotics. Cats with the effusive form may develop a swollen abdomen or difficulty breathing due to fluid accumulation.

Diagnosis of FIP 
As with so many aspects of FIP, diagnostic testing may be problematic. To date, there is no way to screen healthy cats for the risk of developing FIP. Antibody titres are poorly correlated with risk and should not be used to screen healthy cats for risk of FIP. As well as problems with interpretation of these antibody tests, there are problems with laboratory quality control. Finally, cats that have been vaccinated with some types of vaccines may test positive on coronavirus antibody tests due to cross-reaction between components of the cell culture used to produce the vaccine and test system components.

There are newer DNA-based blood tests offered by a few labs that are purported to be FIP-specific. However, these tests often have not been subjected to scientific scrutiny by researchers outside of the labs that offer them. In addition, there are no published studies that have identified a consistent specific genetic difference between FECV and FIPV that could be the basis for a test.

Of great interest is a new PCR test that detects messenger RNA (mRNA) of the M gene of feline coronavirus strains in blood samples. The presence of mRNA indicates active replication of coronavirus in circulating mononuclear cells. A characteristic of FIP virus is that it replicates in mononuclear cells, while the enteric coronavirus replicates in intestinal epithelial cells. This test can be run on blood, effusions, tissue samples and faeces. This test may become a valuable aid in the diagnosis of FIP, but it will take time to evaluate it fully outside of the laboratory setting.

The fact remains that we have no screening test for FIP in well cats. Neither do we have a foolproof way to diagnose FIP in a sick cat. The gold standard remains a biopsy or findings at necropsy. Combining several test results with clinical findings and antibody titre may help rule in or rule out FIP with some degree of certainty. It remains true, however, that a negative antibody titre does not rule out FIP. Nor does a positive antibody titre guarantee a diagnosis of FIP.

Treatment of FIP 
Unfortunately, there is no known effective treatment for cats with FIP. Treatments are aimed at palliative care and improving patient comfort. Drugs that suppress the immune system response to FIPV (such as prednisone) may temporarily stabilize patients. Newer therapies, such as recombinant feline interferon and pentoxifylline, have shown some limited success in a small number of patients but require more investigation before they can be recommended. Sadly, patients eventually deteriorate to the point where humane euthanasia is chosen.