Feline infectious peritonitis (FIP) is caused by a coronavirus called feline coronavirus (FCoV). It is a positive-stranded ribonucleic acid (RNA) virus that infects cats worldwide and is transmitted faecal-orally. It is a coronavirus of the species Alphacoronavirus-1, which includes canine coronavirus and porcine transmissible gastroenteritis coronavirus. According to current knowledge, coronaviruses cannot be passed from infected cats to humans.
Feline coronavirus
Transmission, infection and risk factors
FCoV is a contagious virus, and its major transmission route is faecal-oral. Due to this, faeces is the main source of FCoV infection, and litter trays represent the principal source of infection in groups of cats. Transmission is mainly indirect following oral contact with objects contaminated with faeces, such as litter trays, cat litter fomites and scoops, brushes, vacuum cleaners, shoes, etc, and by grooming paws contaminated when using the litter tray.
Cats begin to shed the virus in their faeces as early as two days after natural infection and will continue to shed for days or months, after which shedding typically stops or occurs intermittently. As immunity is short-lived, shedding can recur due to reinfection in an endemic environment. Some cats can have a persistent infection, shedding the virus for life.
FCoV most commonly affects young (less than two years old) purebred cats from multiple cat households. In fact, FCoV is particularly common in crowded conditions and less common in individually housed, stray or feral cats. A recent history of stress is also common.
Pathophysiology and clinical signs
Feline enteric coronavirus (FeCV) represents most of the feline coronavirus strains that are found in the gastrointestinal tract without causing significant disease. However, infected cats may occasionally show brief bouts of diarrhoea and/or mild upper respiratory signs with spontaneous recovery. A small number of cats can develop mutations of the virus that alter its biological behaviour, allowing the virus to enter the cat’s body through white blood cells (macrophages and monocytes).
The virulence, viral load and immune response of FeCV determine whether FIP will develop; if it does, the virus is referred to as “FIPV”. The intense immune-mediated reaction to FIPV around vessels (phlebitis) causes FIP, with effusions in the abdominal, thoracic and/or pericardial cavities and, in more chronic forms, larger perivascular pyogranulomata on affected organs.
FIP occurs in two forms: non-effusive (dry) with granuloma formations and effusive (wet). Effusions are less common in the dry form, and clinical presentations that include the development of effusions are the most common. The distinction between the two forms of FIP is important for diagnostic purposes because the analysis of effusions is very useful. However, there is a considerable overlap between the two forms.
Feline enteric coronavirus (FeCV) represents most of the feline coronavirus strains that are found in the gastrointestinal tract without causing significant disease
Clinical signs of FIP can change over time, with effusions developing or ocular changes becoming visible on ophthalmoscopic examination. Therefore, repeated physical examinations are important to monitor the progress of the disease.
Neurological feline infectious peritonitis
Up to 30 percent of cats with FIP show neurological signs associated with focal, multifocal or diffuse changes in the brain, spinal cord and meninges. In fact, FIP is a common cause of meningoencephalitis in cats. Neurological involvement is most common with the non-effusive or “dry” form of the disease, either as primary neurological FIP or with neurological signs as part of the overall disease presentation.
The disease often has an insidious onset and can lack distinct clinical signs. Sometimes, cats with FIP present with only neurological disease. FIP induces a pyogranulomatous and immune-complex-mediated vasculitis of the meninges, ependymal lining, periventricular brain tissue and choroid plexus of the central nervous system (CNS). Secondary hydrocephalus can develop due to inflammatory obstruction of the ventricular system. Ocular lesions, such as anterior uveitis, iritis, keratic precipitates, retinitis and anisocoria, have also been identified. Affected cats may also have concurrent systemic signs, including anorexia and weight loss.
Three clinical syndromes were identified in a retrospective study of neurological FIP: T3-L3 myelopathy, central vestibular syndrome and multifocal CNS disease. Common signs include ataxia paresis, hyperaesthesia, nystagmus, seizures, behavioural and mental state changes, and cranial nerve deficits.
Diagnosing neurological feline infectious peritonitis
The European Advisory Board on Cat Diseases has created a diagnostic approach tool that includes an overview of the criteria necessary to confirm or make a diagnosis of FIP very likely (Tasker et al., 2022). Now that effective antivirals for the treatment of FIP exist, trial treatments of cases that are very likely but not yet confirmed can be warranted as the response is usually rapid.
In the absence of confirmatory testing, the integration of multiple test results is most useful to help direct the clinician to a diagnosis of FIP being very likely.
Advanced imaging
Advanced imaging with computed tomography (CT) and/or magnetic resonance imaging (MRI) of the central nervous system to assess the potential risk of herniation is indicated before performing cerebrospinal fluid (CSF) collection. MRI is more sensitive than CT for the detection of subtle intraparenchymal lesions. It often reveals the presence of ventricular dilatation (obstructive hydrocephalus), periventricular contrast enhancement, syringomyelia, cerebellar herniation, and marked contrast enhancement of the meninges, third ventricle, mesencephalic aqueduct and brainstem.
Sampling and analysis
Haematology can be used to test for FIP in cats because haematological changes, such as anaemia, leucocytosis and hyperglobulinaemia, often occur as a result of FIP. However, no abnormalities are present in some affected cats. Serum anti-coronavirus antibodies are often found, but the tests have low specificity. A negative serum titre does not exclude the possibility of FIP-associated neurological disease as immune complexes can escape detection by standard tests.
A negative serum titre does not exclude the possibility of FIP-associated neurological disease as immune complexes can escape detection by standard tests
CSF analysis can reveal marked neutrophilic to pyogranulomatous pleocytosis, with cell counts in the hundreds, and an associated increase in protein concentration (over 200mg/dl). However, CSF can also be normal, show mild mononuclear pleocytosis or have a normal cell count and elevated protein concentration. Positive CSF titres can be used as an antemortem indicator of neurological disease but must be interpreted giving consideration to the integrity of the blood–brain barrier. PCR assays of CSF samples have not been shown to be reliable for confirming disease, and FCoV antibody testing has been performed on CSF samples with FIP with varied results. A combination of FCoV RT-PCR and antibody testing could be helpful to support a diagnosis of FIP, but the small volumes of CSF obtained often preclude antibody analysis.
Ultrasound-guided sampling of an effusion (for cytology, biochemistry and FCoV antigen or FCoV RNA analysis), when present, is the most useful diagnostic step for FIP. Alternatively, fine-needle aspirates (FNAs) of affected organs (for cytology and FCoV RNA analysis) are helpful when effusions are absent. Definitive diagnosis usually requires the analysis of consistent histopathological changes in affected tissues with positive FCoV antigen immunostaining.
Treatment for neurological feline infectious peritonitis
Antivirals (typically the nucleoside analogue GS-441524) are now available to treat cats diagnosed with FIP infection. The recent development and availability of curative antiviral drugs, although expensive and not yet legally available in all countries, has revolutionised the approach to and outcome of FIP treatment. Success rates of 81 to 100 percent have been reported in cats treated with different preparations of compounds containing GS-441524. Very effective oral preparations are available; in most studies, treatment lasts for 84 days, but shorter courses might also be effective.
The recent development and availability of curative antiviral drugs, although expensive and not yet legally available in all countries, has revolutionised the approach to and outcome of FIP treatment
Transient side effects of GS-441524-containing treatments include elevations in alanine transaminase (ALT), eosinophilia and lymphocytosis. Hyperbilirubinaemia, hyperproteinaemia and leucocyte abnormalities usually normalise within a few weeks, and good appetite, activity level, higher temperature, lower bilirubin concentration and normalisation of α1-acid glycoprotein (AGP) are useful for predicting survival.
Although glucocorticoids have been used to treat FIP palliatively in the past, they should be avoided as they seem to worsen outcomes.
Supportive nursing care, including analgesia, non-steroidal anti-inflammatories, intravenous fluids, appetite stimulants, anti-emetics and vitamin B12, is essential to the recovery of cats severely affected by FIP.
Conclusion
FIP has a very poor prognosis with a short survival time if prompt treatment with antivirals is not given. When effusions are present, the disease progression is often quite fast (a few days or weeks). However, when effusions are not present, the disease is more difficult to diagnose and tends to be more chronic (over a few weeks to months). Currently, clinicians need diagnostic tools to help quickly determine the likelihood of a diagnosis of FIP so effective antivirals can be used as soon as possible where available.
