Update on feline infectious peritonitis (Proceedings)

Despite improvements in our understanding of the pathogenesis of FIP, FIP remains a leading cause of death in young cats, especially purebred catteries, shelters.

The virus that causes FIP, feline coronavirus, is an enveloped RNA virus. Feline coronaviruses are divided into two groups:

• Highly pathogenic, feline infectious peritonitis viruses (FIPV)

• Feline enteric coronaviruses, which generally cause mild enteritis (FECV).

There viruses CANNOT as yet be distinguished from one another.

Feline coronaviruses mutate readily and it is now accepted that FECV eventually mutates to form virulent FIPV. Mutation occurs soon after infection with FECV, or years later.

Epidemiology

Seroprevalence of feline coronavirus is 25% in single cat households and 75% to 100% in multicat households. Mortality rate in single/two cat households is 1/5000, in catteries it can reach 5%. Rarely, epidemics of FIP occur in catteries.

The incidence of FIP is related to levels of virus in the environment, virus factors and host factors. Immunosuppression resulting from overcrowding and stress and genetic factors are important. Purebred cats are more susceptible, cats are usually aged 3 months to 3 years; occasionally they are > 10 years, presumably due to poor immune function. Maternal antibody wanes at about 6 weeks of age.

Transmission

Spread of FcoV is FECAL-ORAL, and the virus is very infectious. Some strains remain infective for weeks at room temperature. Most cats shed intermittently, with cycles of recovery and reinfection. Some shed chronically; these cats are important in maintaining the incidence of FIP

Pathogenesis

FECV replicates in enterocytes and destroys the villus tips, with sometimes mild fever, small bowel diarrhea, and vomiting. FECV eventually mutates to virulent FIPV, which is able to multiply in MACROPHAGES!! Infected monocytes deposit in the endothelial lining of small venules. With a strong cell-mediated immune (CMI) response, the virus is eliminated or latent infection occurs. Stress can reactivate the infection, with development of fulminant FIP.

If CMI is not mounted, PYOGRANULOMATOUS VASCULITIS results due to deposition antigen-antibody complexes in the venular endothelium. Pleural and peritoneal effusion develop (= EFFUSIVE FORM). With partial CMI, viral replication slows ® granuloma formation (= NONEFFUSIVE FORM). This may deteriorate to wet FIP if the CMI response wanes.

ANTIBODY-DEPENDENT DISEASE ENHANCEMENT (ADDE) is the term referring to acceleration of disease by the humoral immune response. Antibodies bind to Fc receptors on macrophages with more rapid viral replication and dissemination. This has implications for vaccination. Production of antibodies is essential for disease to occur, as FIP is an immune-complex disease.

Diagnosis

Antemortem diagnosis of FIP is like completing a jigsaw puzzle. It is the combination of abnormalities that is often useful. Clinicopathologic findings include:

• CBC: nonregenerative anemia; neutrophilia, lymphopenia.

• Serum chemistry and urinalysis:

• Proteinuria, azotemia.

• Elevated liver enzymes, coagulopathies

• Many (but not all) cases have hyperproteinemia

• In cats with neuro signs, CSF may show hyperproteinemia and increased neutrophils and lymphocytes (but usually it does not).

• Effusion fluid: sometimes (but not always) it is high protein (5 to 12 g/dL), thick and tenacious (an EXUDATE). Clear to yellow, may contain fibrin clots. Cellularity is low. Predominant cells are neutrophils (also may see mononuclear cells). Rivalta's test can help differentiate exudates from transudates, but is still not specific for FIP in any one cat.

Serology

SEROLOGY is NOT an FIP TEST. It does not test for FIP!!! Positive results ONLY mean EXPOSURE to a coronavirus such as CCV and FCoV. No test is able to differentiate between virulent and avirulent strains, determine whether a cat is immune or susceptible to disease, or whether a cat is shedding coronavirus or not. Titers can be very high in healthy cats, and low in cats with FIP (< 1:100). Recent FIP vaccination can also result in a positive test. Paired titers are not helpful. You also cannot compare results between different laboratories. Less than 4% of cats with FIP have a negative antibody titer, so a negative titer can sometimes help to rule out FIP. Some labs do not report low positive titers, which may be significant.

The 7b region has been correlated with increased virulence in some studies. A 7B protein ELISA test is available, named the FIPSE (FIP-specific ELISA test). Recent studies have shown that some FIPV do not have 7B and some FECVs do have it, so this test is not specific for FIPV.

RT-PCR

RT-PCR cannot be used on serum and feces to differentiate between FIPV and FECV. The genomes of FECV and FIPV are almost identical, and it is not always the same mutation that causes increased virulence. Some FECVs are capable of systemic invasion, so healthy cats can thus have FcoV RNA in their plasma, and probably also in effusion fluid. RT-PCR can be used on tissues and effusion to aid diagnosis, but histopath may be adequate. Recently a PCR for replicating virus in macrophages has been developed, but more studies are required to determine the specificity of this assay.

Antemortem Diagnosis

FIP is often diagnosed at necropsy. The gold standard for antemortem diagnosis is histopathologic exam of biopsy specimens, the characteristic lesion being disseminated pyogranulomatous vasculitis. Immunohistochemistry can be used to demonstrate virus in these specimens. Immunocytochemistry on cells in CSF and fluid may help. A PRESUMPTIVE antemortem diagnosis can be made based on signalment, housing history, eliminating other differentials and a combination of clinicopathologic abnormalities.

Treatment

FIP is 95% fatal despite treatment. Survival time is typically 5-7 weeks, although it varies from days to 6-8 months. Supportive care is important, including feeding tube placement, SC/ IV fluids, periodic thoracocentesis to relieve tachypnea, +/- broad spectrum antimicrobials. Anti-inflammatory and immunosuppressive medications may help to suppress vasculitis. Cats with effusive disease that are not anorectic and are still in good condition usually respond best to these drugs.

• Glucocorticoids (prednisolone 2 mg/kg PO q24h)

• Cytotoxic drugs –chlorambucil (2 mg PO q48h). The CBC must be monitored every 2 weeks in these cats.

In practice, parenteral and oral (-interferon and other antivirals have also been used, with debatable benefit. Some advocate using pentoxifylline, although controlled studies evaluating the benefit of this drug have not been performed. Unfortunately, despite encouraging anecdotal reports, a recent study from Europe showed that recombinant feline interferon did not have a beneficial effect.

Prevention

Multicat households that are seropositive

• Control fecal contamination, stress, fomite transmission, other disease, cat numbers (< 10 cats), one litterbox/2 cats. Keep cats in stable groups of 3 or 4.

• The prevalence of high frequency shedders in a cattery is the most significant risk factor for FIP incidence, so eliminating these cats could help control disease. These cats are detected by serial RT-PCR evaluation of fecal samples; cats must be positive for = 8 consecutive months.

Single cat households

• Incidence of clinical FIP in single cat households is only 1 in 5000 cats.

• Seropositive cats usually become seronegative within 6 months to a year unless exposed to other infected cats.

Vaccination

The FIP vaccine is a temperature sensitive mutant. It is given intranasally, and only replicates locally. Vaccination leads to a systemic response. It is recommended that only seronegative cats in cattery situations be vaccinated, and the vaccine is licensed for use from 16 weeks of age. Unfortunately, in a cattery situation, 50% of kittens have already been infected by this age. Whether or not this vaccine is capable of accelerating disease in the field is unclear.