FELINE INFECTIOUS PERITONITIS
MARIE-PIERRE RYSER -DEGIORGIS
Centre for Fish and Wildlife Health, Institute of Animal Pathology, Department of Infectious Diseases and Pathobiol- ogy, Vetsuisse Faculty, University of Bern, Bern, Switzerland Feline infectious peritonitis (FIP) is a fatal immune- mediated disease of felids, characterized by vasculitis and granulomatous inflammatory reactions1-4).
Infectious Diseases of Wild Mammals and Birds in Europe, First Edition. Edited by Dolores Gavier-Widen, J. Paul Duff, and Anna Meredith. © 2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.
AETIOLOGY
Feline coronavirus (FCoV) is closely related to the transmissible gastroenteritis virus (TGEV) of pigs and Canine coronavirus (CCV), and exists in two forms (biotypes): feline enteric coronavirus (FECV), which replicates in enterocytes and is virtually non-pathogenic; and feline infectious peritonitis virus (FIPV), which has a broader cell spectrum, including macrophages, and causes fatal disease. It is widely accepted that FIPV arises by mutation from FECV in the gastrointestinal tract of an infected cat, then spreading systemically and causing FIP; an alternative hypothesis is that two strains, a virulent one and an aviru- lent one, simultaneously circulate in cat populations1-4’5). Depending on their antigenic relationship to CCV, FCoV strains can be classified into the subtypes serotype I (not neutralized by antibodies against CCV) and serotype II (neutralized by antibodies against CCV), the latter being suspected to have arisen by recombination between FCoV serotype I and CCV. Both serotypes can cause FIP, but most cats with FIP are infected with FCoV serotype I(4,5).
EPIDEMIOLOGY
FCoV is distributed worldwide. Both FIP and exposure to FcoV have been reported in several non-domestic felids, in captivity and in the wild(6’7) (Table 17.1).
Cheetah seem to be particularly vulnerable, even more so than domestic cats(15). In Europe, very low seroprevalences have been reported in free-ranging populations of European wildcat (Felissilvestris) and Eurasian lynx (Lynxlynx), and infection with FCoV in these species is considered not to be maintained, owing to their solitary social system(10’12). FCoV is endemic in environments in which many cats are kept together in a small space but is relatively rare in free- roaming cats, because they usually have a predominantly solitary life without close contact with other cats — most importantly, they do not share the same locations (latrines) for their faeces, which is the major route of transmission in multiple-cat households1-4). A recent survey in the Iberian lynx (Lynxpardinus), which is also a solitary felid, revealed 16% and 40% seropositive lynx, depending on which population they originated from (Table 17.1). This higher seroprevalence was attributed to higher densities and closer contacts with domestic cats(14). However, seroprevalence in wildcats is also low, although contacts between wildcats and domestic cats (including hybridization) are relatively frequent. The fact that the Iberian lynx uses latrines may play a major role in the exposure to FCoV in this species(7).I n the domesticated cat the risk of developing FIP is higher for males and for young and immunocompromised cats, because FCoV replication in these animals is less controlled and the critical FECV mutation is more likely to occur. Studies in purebred catteries showed that susceptibility to FIP is heritable, and although not completely understood, genetic factors appear to increase the risk of developing FIP. Environmental factors play an important role, including re-infection rate in multiple-cat households and stress1-4,15). Concurrent Feline leukemia virus (FeLV) infection can greatly increase the clinical incidence of FIP(16).
Although the Iberian lynx has been shown to be vulnerable to feline viral diseases1-14) and concern has been raised regarding possible impairment of their immune system, no case of FIP has been documented in this species so far, either in the wild or in captivity, despite relatively high exposure rate to FCoV. By contrast, clinical disease has been reported in captive wildcats1-17) and Eurasian lynx(18).TABLE 17.1 Documented investigations of FCoV exposure in free-ranging wild felids in Europe.
| Species | Country | Study period | FCoV Ab prevalence, % (N tested) | FCoV viral RNA, % (N tested) | Reference |
| European wildcat | UK (Scotland) | 1982-1990 | 0 (23) | 8 | |
| (Felis silvestris) | UK (Scotland) | 1992-1997 | 6(50) | 9 | |
| Switzerland | 1996-1997 | 0 (9) | 0 (9) | 10 | |
| France | 1996-1997 | 6 (34) | 1 (22) | 10 | |
| Germany | 1996-1997 | 0 (8) | 0 (8) | 10 | |
| Spain | 1991-1993 | 0 (22) | 11 | ||
| Eurasian lynx | Sweden | 1993-1999 | 0 (102) | 12 | |
| (Lynx lynx) | Switzerland | prior to 2005 | 4.6 (65) | Ryser-Degiorgis | |
| (unpublished data) | |||||
| Iberian lynx | Spain (Donana and | 1989-2000 | 0% (37) | 13 | |
| (Lynx | Sierra Morena) | ||||
| pardinus) | Spain (Donana) | 2003-2007 | 16% (44) | 0% (45) | 14 |
| Spain (Sierra Morena) | 2003-2007 | 40% (30) | 0% (32) | 14 |
Infection usually takes place oronasally through FCoV- containing faeces, although other routes have also been documented, e.g.
through saliva, urine or transplacental infection. FIPV has not been found in secretions or excretions of cats with FIP, and transmission of the mutated FCoV inducing FIP is considered unlikely under natural circumstances. Iatrogenic transmission may occur, however(4,16). FCoV is a relatively fragile virus, but in dry conditions it has been shown to survive for up to 7 weeks outside the host, and indirect transmission through clothes and other fomites is possible. Many naturally infected healthy carrier cats shed FCoV for at least up to 10 months, sometimes even throughout life(4).PATHOGENESIS, PATHOLOGY AND IMMUNITY
Approximately 2 weeks after the mutation from FECV to FIPV has occurred, mutated viruses are found in various organs, including spleen, liver and central nervous system. Complement and inflammatory mediators are released from infected macrophages and cause lesions. Two different forms of FIP have been identified. Cats with a poor cell-mediated immune response develop an effusive, exudative wet form, which is an immune-complex vasculitis that causes leakage of protein- rich fluid from the blood vessels into the body cavities. In cats with partial cell- mediated immunity, a non-effusive non-exudative dry form develops, characterized by granulomatous lesions in multiple tissues. Frequently, however, dry FIP is often preceded by a brief episode of wet FIP, and may also become effusive in the terminal stages of the disease, when the immune system response fails(16).
Peritonitis, pleuritis and pericarditis with effusions characterized by very high protein content and granulomatous changes are typical(4-6,17,19). Involvement of the eyes and/ or central nervous system predominates in cats with dry FIP. Generalized synovitis is frequent. Hydrocephalus and orchitis may occur(16). Histologically, there are mainly perivascular infiltrations of mixed inflammatory cells, granulomas and multifocal necrosis in various organs, and lymphoid depletion.
Wet FIP is characterized by perivascular pyogranulomas consisting of aggregates of macrophages filled with virus and surrounded mainly by neutrophils and oedema. The lesions of dry FIP consist of more classic’ granulomas, mainly located at the surface of organs, with small foci of macrophages in the centre, many of which contain no or small amounts of viral antigen, surrounded by broad bands of lymphocytes and plasma cells(16).CLINICAL SIGNS AND TREATMENT
Clinical signs appear to be similar in wild felids and domestic cats, although reports are scarce in the former. Most FCoV infections are subclinical. However, after initial FCoV infection, transient mild upper respiratory signs, mild diarrhoea and/or vomiting may be observed in domestic cats. Severe enteric disease with weight loss rarely
(4,5)
occurs().
Clinical signs of FIP are variable and unspecific, because many organs can be involved1-4,5,17,19). In felids with ascites, abdominal swelling is common. Thoracic effusions usually manifest with dyspnoea and tachypnoea, together with muffled heart sounds heard during auscultation. Lethargy, fever, anorexia and weight loss, icterus, diarrhoea, vomiting and obstipation may occur. Abdominal palpation may reveal enlarged mesenteric lymph nodes, thickened loops of intestine, hepatomegaly and irregular shaped or enlarged kidneys. Ocular changes (in retina, uvea and iris) are common. The most frequently observed neurological disorders include ataxia, nystagmus and seizures.
Virtually every cat with confirmed FIP dies(4,17,19). There is no effective treatment and no effective vaccine.
DIAGNOSIS
Diagnostic options in domestic cats have been reviewed in detail(4,5,16), and information on wild felids is largely in agreement with them. Ante mortem diagnosis of FIP is extremely challenging, owing to the lack of specific clinical signs, the lack of pathognomonic haematological and biochemical abnormalities, and low sensitivity and specificity of routine diagnostic tests.
The albumin- globulin ratio, characterized by a decrease of albumin (liver failure, protein loss e.g. due to nephrotic glomerulopathy, or vasculitis) and an increase in globulin, seem to have the best diagnostic value, a ratio lower than 0.6 strongly indicating FIP in domestic cats. For definitive diagnosis, a post mortem examination is required, with the demonstration of FIP- positive macrophages by immunostaining in addition to the presence of typical histological changes.Presence of enteric FCoV can be diagnosed by reverse transcription polymerase chain reaction (RT-PCR) or electron microscopy in faeces, and by immunohistochemical or the immunofluorescent staining of intestinal biopsies. RT- PCR on faeces is useful for documenting viral shedding; the strength of the RT- PCR signal correlates with the amount of the virus present in the intestine. However, as shedding is variable, repeated PCR should be performed daily over 4—5 days for an accurate result. Freezing samples may lead to false-negative results.
Results from serological assays (usually immunofluorescence) must be interpreted with caution. Antibody titres may significantly vary with different methodologies. Also, a large percentage of healthy felids are FCoV antibodypositive with high and rising titres without ever developing FIP, and the absence of antibodies excludes neither infection nor disease. However, a healthy animal without antibodies is considered likely to be free from FCoV. The height of the antibody titre generally correlates well with the amount of virus shed in the faeces. RT- PCR can be performed on blood, but it does not distinguish infection between mutated and non-mutated virus, and falsepositive and false-negative reactions may also occur.
MANAGEMENT AND CONTROL
Avoidance of overcrowding and maintenance of a larger proportion of older cats helps to minimize population loads of FCoV Small groups can spontaneously and naturally become FCoV-free(4).
Antibody testing is recommended to screen felids before their introduction into a FCoV-free environment. Thorough cleaning and sanitizing of potentially contaminated holding facilities is required1-4’19’2101. FCoV is destroyed by most household disinfectants and detergents. There should be a 3-month delay before introducing a new, FCoV-free cat into a potentially contaminated environment. Because stress from capture, confinement and transport may compromise disease resistance, translocation procedures should aim to limit the stress associated with human exposure and the holding time of wild felids before release(7’20).
SIGNIFICANCE AND IMPLICATIONS FOR ANIMAL HEALTH
Although FCoV infection has been widely documented in domestic cats and wild felids, FIP appears to be a serious issue only in the captive environment. An impact on free- ranging wild felid populations has not been documented to date(7).
TRANSMISSIBLE GASTROENTERITIS [24] [25] usually present only transient inappetence and diarrhoea. Viral detection and/or serology are needed to confirm diagnosis. Cross-reactions with PRCV are common in serologic assays, and results should be interpreted considering clinical signs (enteric versus respiratory signs) and disease history of the herd(21).
TGE is widespread worldwide in domestic pigs and can cause severe economic losses. There is neither specific treatment nor an effective vaccine. As a preventive measure, it is recommended to introduce swine into a herd only if they come from a farm free of TGE, are serologically negative, and/or have been placed in isolation for 2—4 weeks(21).
CANINE RESPIRATORY CORONAVIRUS INFECTION viral replication in the upper respiratory tract may damage the mucociliar system, leading to concurrent infections by opportunistic pathogens(27). CRCoV diagnosis is mainly based on virus detection by virus isolation, haemagglutination and PCR-based methods. At the moment, there are no specific therapeutic protocols nor prophylactic strategies against CRCoV infection. CRCoV is a dog pathogen without ascertained epidemiological and pathogenetic roles in wildlife. Although the infection is currently restricted to domestic dogs, a potential transmission to humans cannot be ruled out, considering that other BCoV-like viruses have already passed the species barrier, acquiring the ability to infect human hosts.