Feline Infectious Peritonitis (FIP)
Fred W. Scott, D.V.M.,
Profecssor of Veterinary Virology, Department of Microbiology, Immunology and Parasitology,
College of Veterinary Medicine, Cornell University; Fomer Director, Cornell Feline Health Center
James R. Richards, DVM
Director, Cornell Feline Health Center, College of Veterinary Medicine, Cornell University
Barlough, D.V.M., Ph.D
Dilpomate, American College of Veterinary Microbiologists
Feline infectious peritonitis (FIP) is an important and complex disease of cats caused by a virus belonging to the family Coronaviridae. Coronaviruses are a large and widely distributed group of RNA viruses and are important causes of disease in birds and mammals. Feline coronavirus (FCoV) infections appear to be restricted to members of the cat family, including domestic breeds as well as certain exotic species: sand cats, caracals, lynx, cougars, cheetahs, jaguars, leopards, and lions. in addition to FCoV, cats are susceptible to infection with several other viruses in this group, including canine coronavirus (CCV) and the swine agent, transmissible gastroenteritis virus (TGEV).
THE CAUSE. Different
strains of FCoV possess different virulences (disease-causing ability). Some strains that
have been isolated and grown in a laboratory are avirulent or of low virulence (strains
commonly known as feline enteric coronavirus or FECV), whereas other strains produce FIP
(strains commonly known as feline infectious peritonitis virus or FIPV). FECV strains
typically produce disturbances of the digestive tract that affect only a minority of
infected cats-usually very young kittens.
Feline coronavirus infections are extremely common in multicat environments. in densely housed groups of cats, it is not unusual to find that most cats -up to 80 to 90 percent in some situations-have been exposed to FCoV. in households with only one or two cats, the risk of FCoV exposure is much lower. As a result, FIP is rare in households with few cats, with estimates as low as I cat in 5000. However, in households with high population densities, FIP deaths may reach 5 percent or higher. As one way of explaining the sporadic nature of the disease, some researchers speculate that FIPV may be an in vivo (within the living body) mutation of the more common FECV. The ability of the individual cat to mount an effective immune response is also believed to be a major factor determining FIP development.
The routes by which FCoV is spread from cat to cat have not been identified with absolute certainty, but it is most likely that initial infection results from ingestion or inhalation of the virus. Close contact with infected cats or their excreta is usually required for efficient virus transmission. Transmission across the placenta to the developing fetus is suggested by occasional observations of FIP in stillborn kittens, but the frequency with which this occurs is unknown.
In common with many other viruses of this type, FCoV is relatively unstable outside the host and is rapidly inactivated by many common soaps, detergents, and disinfecting agents. Household bleach diluted 1:32 in water has been recommended for decontamination purposes.
PATHOGENESIS. Studies performed over the past several years have succeeded in identifying some of the major host-virus interactions of FIPV infection. After infection of white blood cells (leukocytes) within lymphoid tissue at or near the site of initial virus penetration, a primary viremia. involving virus and/or virus-infected cells occurs within one week after exposure. In this way, virus is transported to other areas of the body, especially to organs such as liver, spleen, and lymph nodes. These structures contain large populations of certain leukocytes, such as macrophages, which appear to be primary target cells for FIPV infection. Blood-borne spread of virus also results in infection of circulating white blood cells (monocytes) and, importantly, in localization of virus and virus-infected cells within the walls of small blood vessels. A secondary viremia may occur after initial infection of target tissues and result in further spread of virus throughout the body. Deposition of virus, virus-infected white blood cells, and virus-antibody complexes within blood vessel walls produces an intense, destructive inflammatory response (vasculitis), which damages vessels and allows the escape of fluid components of blood into intercellular spaces, eventually accumulating as characteristic "FIP fluid" within body cavities.
CLINICAL SIGNS. Though it is possible that mild cases of FIP that spontaneously resolve may occasionally occur, this is considered a rarity. Virtually all cats with FIP will die.
Most cases of FIP occur in cats less than three or four years of age. The onset of clinical signs may be sudden (especially in kittens) or it may be slow and insidious, with the severity of signs gradually increasing over a period of weeks. Some of these signs may be quite nonspecific: intermittent inappetence, depression, weight loss, fever. In many cases, affected cats may continue to eat and remain alert and responsive for a considerable period of time; however, fever (which may fluctuate at different times of the day) is a constant finding and usually persists until the last few hours of life.
The two major forms of FIP can be distinguished on the basis of fluid accumulatiom-the presence of fluid in one or more body cavities in effusive ("wet") FIP, and its absence in noneffusive' ("dry") FIP. Effusive FIP is the more fulminant (sudden and severe) form of the disease, with a more rapid onset and shorter clinical course than the noneffusive form.
An accumulation of fluid within the abdorninal cavity, with progressive, painless enlargetnent of the abdomen, is probably the most common clinical manifestation of effusive FIP. Respiratory distress may develop when abdominal fluid accumulation is excessive or, more commonly, when accumulation of fluid occurs within the chest cavity, resulting in compression of the lungs. Other signs that may be seen include jaundice (yellowing of the mucous membranes and skin)
and a mild anemia (low red blood cell count). This anemia be exacerbated by coinfection with feline leukemia virus or Haemobartonella felis (the organism causing feline infectious anemia).
Gastrointestinal, ocular, and neurologic signs may also occur in cases of effusive FIP. The course of effusive FIP is quite variable, but the usual survival time after onset of clinical signs is about two or three months. Some young kittens may survive for no longer than a few days, whereas some adults may live for six to eight months with active clinical disease.
The onset of noneffusive FIP is often insidious, with clinical signs reflective of involvement of specific organ systems in the FIP inflammatory process. Weight loss, depression, anemia, and fever are almost always present, but fluid accumulation is usually minimal. Clinical signs of kidney failure (such as increased water consumption and urination), liver failure (jaundice, neurologic signs), pancreatic disease (vomiting, diarrhea, voracious appetite, diabetes mellitus), neurologic disease (hind limb incoordination, loss of balance, tremors, behavioral changes, paralysis, seizures), or ocular disease (inflammation of the eye, retinal disease, blindness) may be seen in various combinations in cats with severe organ impairment. The disease course is usually more chronic than in effusive FIP. Some cats, especially those with primary ocular involvement, may survive for as long as a year or more.
FIPV was once incriminated as a possible cause of reproductive problems in breeding queens-infertility, fetal resorptions. (biochemical disintegration of the fetus), abortions, stillbirths, birth of weak "fading" kittens, congenital malformations, and neonatal heart disease (acute congestive cardiomyopathy). There is no conclusive published evidence that the virus plays a role in any of these disease processes. To date, the only disease of neonates known to be caused by FIPV is FIP itself.
DIAGNOSIS. The clinical diagnosis of FIP is made by evaluation of the history and presenting signs and the results of supporting laboratory tests. it must be kept in mind that a definitive diagnosis of FIP can be made only by microscopic examination of tissues either by biopsy or at necropsy. Any diagnosis made in the absence of such examination must be considered presumptive; hence, the vast majority of clinical diagnoses of FIP are presumptive in nature. However, when the clinical signs and laboratory data support a presumptive diagnosis of FIP, then such a diagnosis may be made with a very high degree of confidence, especially when the typical effusion fluid is present. Evaluation of effusion fluid remains one of the most useful diagnostic aids for FIP.
Most cats with FIP have moderate to high titers (levels) of coronavirus antibody, but this finding must not be over-interpreted. The presence of coronavirus antibody in any cat, healthy or diseased, is indicative of only one thing; previous exposure to FCoV or one of the closely related viruses (CCV, TGEV). The antibody test does not prove that a cat has FIP. it therefore follows that the diagnosis of FIP must never be made simply on the basis of a coronavirus antibody test.
The natural reservoir of FCoV appears to be infected cats. The most important source may be clinically healthy carrier cats-those that carry and excrete FCoV but show no ill effects. The problem that arises is that, as of this writing, there are no diagnostic tests for identifying these carriers (i.e., there is no test that is equivalent to the Hardy test, or ELISA test for feline leukemia virus). Thus a cat with a positive antibody test is not necessarily carrying or shedding FCoV. The polymerase chain reaction (PCR) is a powerful tool capable of detecting minute quantities of coronavirus RNA in blood, serum, tissue, or feces. It promises to further the understanding of FIP and the FCoV carrier state. Although as yet not diagnostic for FIP, PCR technology may ultimately lead to an accurate test that can identify contagious cats. PCR is is presently only capable of detecting coronaviruses in general, not necessarily those that cause FIP. The immunoperoxidase test can diagnose FIP more accurately than traditional histopathologic examination because it detects virus-infected cells in the tissue. A biopsy of affected tissue is necessary for evaluation.
TREATMENT. No curative therapy for FIP currently exists; the disease is virtually always fatal once clinical signs have become apparent. Palliative therapy combines high levels of corticosteroids, other immunosuppressive medications, and broad-spectrum antibiotics, in an attempt to slow down the FIP inflammatory disease process and minimize secondary bacterial infections. This therapy serves only to modify the disease course and, in most cases, does not provide a cure. if successful treatment of FIP is to be developed in the future, it will likely involve a combination of medications, including anti-inflammatory or immunosuppressive drugs, immune-modulating medications, and antiviral drugs.
A number of supposed treatments for FIP have been touted in recent years, including experimental medications and megavitamin supplementation. To date, there is no published scientific evidence that any of these potions is of benefit to affected cats.
PREVENTION. Research shows that any cat exposed to FCoV has the potential to develop FIP. If FIPV is indeed an in vivo mutation of a less virulent feline coronavirus, the most successful control strategies will hinge on reducing FCoV infections in general and promoting healthy immunity in cats at risk. Breeders should be advised to remove cats persistently infected with feline leukemia virus or feline immunodeficiency virus, reduce cattery crowding, and develop management strategies that minimize fecal contamination. Because some studies suggest a genetic predisposition for the development of FIP, breeding pairs of cats that tend to produce kittens with FIP should be discouraged.
At this time, there is no practical way to eliminate FCoV infections or prevent FIP from occurring within a group of cats. Although extremely successful in eliminating FeLV infections, a test-and-removal program for healthy coronavirus antibody-positive cats cannot be recommended on the basis of current knowledge. There is no available diagnostic test that can specifically identify carriers of FCoV, so there is no medical reason for destroying healthy antibody-positive cats (i.e., a positive antibody test indicates only past exposure; it does not mean necessarily that a cat is still carrying the virus).
It is believed that the major source of feline coronavirus is the feces of an infected cat, and that other cats become infected by ingesting (or inhaling) the virus. Therefore, minimizing fecal contamination decreases the transmission of the virus from one cat to another in multiple-cat households. Fecal contamination can be reduced by locating litter boxes in easy-to-clean areas distant from food and water dishes. There should be at least one litter box for every two cats, and the litter should be scooped clean of feces once daily. The entire litter box should be cleaned and disinfected at least weekly.
If possible, breeders should consider keeping cats in stable groups of four cats or less. Devoting a special area for pregnant queens, and providing individual queening boxes separate from other cats during parturition and nursing, can reduce transmission of infectious agents to kittens. Maintaining an area where weaned kittens are strictly isolated from all the other cats helps prevent infection during this most susceptible age. Early weaning of kittens-as early as five to six weeks of age-followed by strict isolation from other cats has been shown to markedly reduce FCoV infection of kittens; however, this procedure can succeed only if strict isolation is maintained.