Causes (Genes + virus + stress)

Feline coronavirus (FCoV) infection is extremely common in cats worldwide. In the United Kingdom approximately 40% of the domestic cat population is seropositive and where cats are housed together in multi-cat households, this figure increases still further to around 90%. Natural infections with FCoV are usually transient, although a significant percentage of infections may be persistent. Most infections are asymptomatic or result in mild, self-limiting gastrointestinal disease and in these cases, the causative agent is known as feline enteric coronavirus (FECV). In a small percentage of animals (<5%), however, a fatal, multi-systemic, immune-mediated disease occurs and this is known as feline infectious peritonitis (FIP). The virus associated with FIP is referred to as FIP virus (FIPV) and it is proposed that cats acquire FIPV by mutation of an endogenous FECV. This hypothesis is known as the 'internal mutation theory' and is widely accepted¹. 

There are two types of FCoV that can be distinguished by serology and by sequence analysis. Type I viruses are most prevalent in the field and account for 80% of all infections. Type II viruses are less prevalent and are characterised by recombination events that result in the replacement of the FCoV spike glycoprotein gene with the equivalent gene of canine enteric coronavirus. There is no evidence that either type is more commonly associated with FIP in natural infections¹.

The 'internal mutation theory' states that FIP occurs when a cat is exposed to variants of FCoV that have mutated within the host and are able to disseminate from the gut (primary site of infection) by gaining the ability to replicate efficiently within macrophages. This hypothesis has had many proponents and numerous speculations regarding the location of mutation(s) that could result in the alteration of pathogenicity have been made. It should be noted that the difference between FCoV infection with and without FIP disease is believed to be quantitative rather than absolute. Most authors have concurred that although low-level monocyte-associated viremia is found with FECV infection, this virus is mainly confined to the gut. This is in contrast to the highly pathogenic FIPV, which disseminates systemically with high viral tires¹.

FIPV is relative unstable in the environment but may remain infectious for as long as 7 weeks within dried organic material or on dry surfaces. It is susceptible to most disinfectants.  Coronaviruses are common viruses that normally cause diarrhoea in most animals. In humans the recent SARS outbreak was caused by a coronavirus that was transmitted from animals to humans. No evidence exists to show that FIP causes illness in humans. It appears to be a cat disease only. The feline coronaviruses are related to canine coronavirus (CCV) and transmissible gastroenteritis virus (TGEV) of pigs. Both of these related viruses can infect cats, and experimental inoculation with CCV can cause clinical signs of FIP. Originally, it was thought that there were only two types of feline coronavirus that infected cats, and the more virulent type, FIP virus (FIPV), caused the clinical disease of FIP. It is now known that, in fact, FIPV is a mutant of FECV. Not only can the genetic makeup of the virus impart greater disease-causing potential, but also the cat’s genome can determine the severity of disease. It has been shown that a genetic predisposition can put some cats at greater risk of FIP than others. In one study of a group of Persian cats experiencing an epidemic of FIP, many of the kittens that were affected were found to be sired by the same tom. It has also been observed that cheetahs are at increased risk for FIP infection. This is most likely due to the high degree of homozygosity in its genome. This may create a weaker cell-mediated immune response when compared with other Felidae.

The virus is transmitted via oral and nasal secretions; prolonged contact with an infected cat is usually required for transmission. The incidence of FECV infected cats in a closed population is typically found to be either zero or 80-90%, whereas in the free-roaming population, FECV infections are around 25% of the population. The outcome of infection may not be known for months or years, as the virus may remain dormant. The outcome is influenced by the cat's immune response. Stress, vaccination and concurrent disease can exacerbated and trigger FIP. Antibodies against the FECV virus may promote the disease rather than cause immunity.

Viral pathogenesis

There are four outcomes to feline coronavirus (FCoV) infection: the development of feline infectious peritonitis (FIP, which is immune-mediated), subclinical infection, development of healthy lifelong carriers and a small minority of cats who resist infection. Examination of the FCoV genome has shown that the same strain of virus can produce different clinical manifestations, suggesting that host genetic factors may also play a role in the outcome of infection. FIP is most prevalent amongst pedigree cats, although how much of this is due to them living in large groups (leading to higher virus challenge and stress which predisposes to FIP) and how much is due to genetic susceptibility is not known. If host genetics could be shown to play a role in disease, it may allow the detection of cats with a susceptibility to FIP and the development of increased population resistance through selective breeding. The feline leucocyte antigen (FLA) complex contains many genes that are central to the control of the immune response.

Symptoms

In those cats which develop disease, unexplained fever is probably an invariable first symptom.

It can cause a number of other signs, as well. Lethargy, weight loss, eye disease, swelling of the abdomen or fluid in the chest can all occur with FIP. In adult cats, infection of the brain can also cause neurological signs such as FIP-associated seizures, loss of balance, walking in circles and staggering. Many secondary problems, such as liver or kidney disease can occur with FIP. Any cat with fevers that do not respond to antibiotics should be considered as a candidate for this disease. In any chronic illness in cats for which no other cause can be found, FIP should be considered. 

There are two commonly recognised syndromes associated with feline infectious peritonitis. In the 'wet FIP' cases, fluid accumulates in the abdomen and it can become quite distended. This is known as the effusive form of FIP. The abdominal distension does not appear to be painful. The fluid that builds up in the wet form of FIP is called ascites when it occurs in the abdomen, and pleural effusion when it occurs in the thorax. The fluid is sticky and usually light yellow to golden colour, with a relatively large amount of protein.

Anterior uveitis secondary to FIP	Abdominal distension due to fluid accumulation

The other recognised syndrome is the 'dry' form of FIP, in which the symptoms of fever, weight loss and other clinical signs develop but there is no fluid accumulation. This is the more common form of the disease, especially in kittens.

Diagnosis

Although FIP can be diagnosed from clinical symptoms, a veterinarian will normally take a blood sample to have it tested for FIP antibodies (titres). The standard method of testing for antibodies is a fluorescent antibody test (for further information, download IDEXX report at top of page). The presence of antibodies is one of the common ways to detect FIP. Up until the 1980s, most vets believed that any cat with antibodies to FIP should be euthanized to prevent the disease from spreading. We now know that the presence of FIP does not mean the virus is present. However, an antibody tests that show FIP titres >400 is suspicious, and a titre >800 is suggestive of active disease or a carrier state. Many cats with titres >1600 die from FIP within three months. FIP can also be diagnosed from X-ray:

The disease can only be confirmed accurately by taking tissue samples from major body organs at death (autopsy). This makes it frustrating to the cat owner who wants a clear diagnosis of their sick cat. What the vet can merely suggest at this stage is that if the blood titre is high, a suggestion of FIP is likely, though not conclusive. This is because there are other coronaviruses that affect cats but that do not produce FIP. The most common of these are the feline enteric coronaviruses. The antibodies produced against these other diseases are too similar to FIP virus for current tests to be able to distinguish between them. To make matters worse, a negative titre (no discernible antibodies) to FIP does not rule out the disease. Presently the only accepted definitive diagnosis of FIP requires biopsy of affected tissues obtained at necropsy or from a surgical biopsy. Common necropsy (Fig. 4) findings include icterus, abdominal or pleural effusion, and multifocal, pale pyogranulomatous lesions covering all affected surfaces. Histopathological examination of affected tissues often shows necrogranulomatous inflammation (large areas of necrosis with infiltration by macrophages and neutrophils). Vasculitis will be present, and appears as a vessel surrounded by an area of necrosis bordered by macrophages, lymphocytes, plasma cells, and neutrophils. Immunohistochemistry (IHC) for FCoV can be performed and aids in the definitive diagnosis of FIP.

Fig. 4. The characteristic necropsy findings of FIP consist of a finely granular appearance to the abdominal viscera due to fibrin deposition. There is often effusion present, but it is difficult to see in this picture.

Fig. 5. the inflammatory cells shown (neutrophils, macrophages) are typical of the response to FIP infection. Fig. 6. Kidney, the DAB-stained cells are interpreted to be macrophages that contain coronavirus antigen. 

Treatment

Treatment is usually symptomatic. Most vets prescribe broad-spectrum antibiotics such as Clavulox® or Orbax®. The use of cortisone is debatable. Some vets argue that this drug suppresses the cat's immune system and reduces its ability to fight infection. However, some anecdotal evidence supports slightly greater longevity using this medication. Supportive care such as a well-balanced diet, avoiding stress and overcrowding are vital. Immune stimulating drugs such as Waltham's Immune Support® or vitamin supplements are advised but may only help in the short term. Eventually, cats with FIP succumb to overwhelming infections three to six months after a tentative diagnosis is made. Not all cats that are exposed to the FIP coronavirus will develop the disease. In colonies of cats in which this disease is known to be present, estimates are that 8 to 20% of cats exposed to the virus will develop clinical signs of FIP. The rest of the cats may become immune to the disease or may simply not react to it. The reason that only a relatively small number of cats exposed to the virus develop the disease is unclear. Cats that do not have a strong immune system may be more susceptible to the disease. Many breeder cats are FIP positive yet never show disease. These cats are usually carriers of the disease, shedding the virus in their faeces and urine.  

Controlling FIP in catteries

FIP virus itself lasts in the environment for up to 6 weeks. It is easily killed with disinfectants, so careful cleansing of a household may help prevent the spread of the disease if a cat with FIP is identified in a household with more than one cat. Due to the delay in the appearance of clinical symptoms once infection occurs, it is likely that most cats in a household have been exposed to the virus by the time it becomes evident that one of the cats is sick. Reducing stress levels by resisting overcrowding of cats in a household and providing adequate litter pans may be helpful in reducing the spread of FIP as well. Strict sanitation and isolation of infected cats and all susceptible kittens from each other is one approach. Vaccination is the other. Sanitation appears to be a major factor in preventing the spread of this virus. In catteries with known FIP exposure, it is possible to severely limit the spread of the disease by keeping kittens isolated from adult cats after the age of 6 weeks and following good sanitary practices. If kittens are not exposed to other cats in the household after six weeks of age, there is a very good chance that they can avoid infection. Once they go to a home where they are the only cat, there is little chance that they will be exposed to the virus. Because FIP is a disease of the immune system, it is also important to ensure the cats are fully vaccinated against cat flu and Chlamydia, and regular wormed and flea-treated, as any disease is likely to reduce a cat's health.  

Vaccination

No vaccine is available in Australia against FIP. Though it is available in the USA, its effectiveness is still open to debate.

1. Dye, C & Siddell, SG (2007) Genomic RNA sequence of feline cornavirus strain FCoV C1Je.  Journal of feline medicine and surgery 9:202-213

Further information on FIP available at http://www.dr-addie.com/

Additional information also at http://www.vspn.net/VSPNsearch/VINLibrary/lv960028.htm