FIP (Feline Infectious Peritonitis) Overview
Feline coronavirus disease is a subject of considerable controversy and confusion. Cats are susceptible to infection with several members of the coronavirus group including porcine transmissible gastroenteritis virus (TGEV), canine coronavirus (CCV), and feline coronaviruses.1-4Infection with TGEV or CCV causes inapparent infection and seroconversion (development of coronavirus antibodies) in cats under experimental conditions, however, natural infection with these viruses is probably rare.1,3 However, canine coronavirus has been found to produce a syndrome that is clinically identical to FIP under experimental conditions. Many antigenically similar feline coronavirus (FCoV) strains have been isolated from domestic cats.4,5 Feline coronaviruses vary widely in their spectrum of infectivity and virulence. Feline coronavirus isolates of low virulence that are not systemically invasive and replicate only in mature intestinal epithelial cells have been called feline enteric coronaviruses (FECV).4,5 Feline enteric coronaviruses usually cause only mild, self-limiting diarrheic illness in young cats. More virulent, invasive strains of feline coronavirus produce the clinical disease syndrome called feline infectious peritonitis (FIP) and these virulent isolates are known as feline infectious peritonitis viruses (FIPV).3,4 Virulence varies markedly among the FIPVs because some FIPV isolates consistently produce severe disease and others rarely do so.3,4 The virulence of FIPVs is apparently related to their ability to infect and replicate within macrophages.3-5 The “S” protein on the viral envelope is believed to be responsible for viral attachment, membrane fusion, and virus-neutralizing antibody production.6 However, this distinction is artificial and there is considerable experimental evidence accumulating that apparently “enteric” intestinal coronaviruses rapidly mutate and can develop the pathologic and invasive characteristics of “FIP-type” coronaviruses.5a This most likely accounts for the sporadic occurrence of FIP in coronavirus endemic catteries as well as in cats living in isolated environments that develop FIP late in life. There is also evidence that these “enteric” viruses can be found in systemic circulation thus confounding interpretation of even highly sensitive tests like the PCR.5b Recent studies of cat populations with endemic coronavirus infection (eg, catteries) have demonstrated that the major risk factors for the occurrence of FIP are cat population density, the presence and magnitude of coronavirus shedding individuals in the population, and the concentration of genetically more FIP-susceptible lines of cats in the population.5c It is likely that it is the infection and reinfection with coronaviruses generally among cats (as opposed to the spread of an “FIP” virus among cats) that is responsible for the occurrence of FIP in an individual. Any cat that carries any coronavirus is potentially at risk for developing FIP and 30% of household pet cats and 80-90% of cattery cats carry feline coronavirus. Epizootiology FCoV is shed in the secretions and excretions of infected cats.7,8 Feces and oropharyngeal secretions are the most likely sources of infectious virus because large quantities of FCoV are shed from these sites early in the course of infection, usually before clinical signs of FIP appear.8,9Infection is acquired from acutely infected cats by the fecal-oral, oral-oral, or oral-nasal route.8 Contrary to earlier reports10, recent evidence suggests that FCoV is relatively stable in the environment.9 Dried virus in a 21o C (70o F) environment can remain infectious for at least six weeks.9 Under ideal conditions, fomites and environmental contamination may be sources of contagion for several months. Fortunately, FCoV is readily destroyed by most common disinfectants and detergents and thorough cleaning will substantially reduce the concentration of infectious virus.10 FIP affects both wild and domestic cats.10 In domestic cats, males and females are affected equally but the incidence of FIP is age related and biphasic.10 Cats 6 to 12 months of age have the highest incidence, probably because of exposure and infection of young, susceptible individuals.10 FIP remains fairly common in cats up to 5 years of age but there is a noticeable decline in the incidence of disease in middle age.10 FIP incidence increases again in cats over 13 years10, perhaps due to a decline in cell-mediated immunity (CMI) in these aged individuals. FIP tends to affect cats bred and/or raised in catteries or multiple cat environments more frequently than those from single cat households. Multiple cat environments are more likely to contain shedding FCoV carrier cats and environmental sources of infectious virus resulting in prolonged exposure of susceptible kittens. Stress, crowding, poor sanitation, parasitism, and concurrent diseases, particularly immunosuppressive diseases such as feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV), may also increase the impact of FIPV on cats in these environments. Pathogenesis Course of infection Experimental studies show that FIPV is found in the tonsils and small intestinal mucosa within 24 hours of ingestion.7 Viral infection of the cecum, colon, mesenteric lymph nodes, and liver occurs over the next 14 days.7 Further systemic spread to any body organ or system occurs as the disease progresses. Feline infectious peritonitis is an immune complex mediated disease and systemic antibodies are not protective.4,5,9,11 Pre-existing circulating coronavirus antibodies accelerate disease symptoms and cats do not die of FIP unless and until they make antibodies to the virus (antibody-dependent enhancement, ADE).4-6 In ADE, binding or opsonization of virus-antibody complexes by monocytes or macrophages results in infection of these cells rather than virus neutralization.6 Virus-infected phagocytic cells disseminate FIPV infection to distant sites.5 The course of disease appears to be established very quickly following pathogenic FCoV infection. The development of CMI is the most crucial factor in determining the ultimate outcome of FIPV infection.4,5,12 Cats that produce humoral antibodies but fail to generate an effective CMI response develop effusive FIP.4,5 Experimental evidence demonstrates that cats with non-effusive FIP often have preceding, transient effusive disease.4 Thus, noneffusive FIP is believed to result from a partially protective CMI response that is unable to wall off and contain the virus.4 Cats that mount a successful and rapid CMI response apparently do not develop active pathogenic FCoV disease although they may harbor latent virus for some period of time.4,5 In fact, the presence of low level of viremia apparently maintains their CMI status (premunition immunity).4These recovered “immune carriers” are not ill but may have the potential to reactivate their latent infection if immunosuppressed.4 Although not proven under experimental conditions, it is suspected that immune carriers may periodically shed infectious FCoV and may be a source of