Feline Infectious Peritonitis (FIP)

Feline Infectious Peritonitis (FIP) is considered the main cause of death related to an infectious disease in the cat; FIP is the uncommon consequence of the infection induced by Feline Coronavirus (FCoV) and indeed the majority of cats that come into contact with the virus remain asymptomatic. As recommended by the ABCD (The European Advisory Board on Cat Diseases), by FCoV we conventionally mean the virus, while the disease is called FIP.

VIRUS CHARACTERISTICS

Feline Coronaviruses belong to the order Nidovirales and consist in RNA viruses. Like many RNA viruses, FCoV is relatively sensitive to common disinfectants and to heat and, in the absence of carrier cats, it survives in the environment for less than 24 hours.

FCoVs usually behave like normal inhabitants of the intestinal tract: they colonise the intestinal epithelium, where they replicate and tend to reach an equilibrium with the immune system of the host; their presence is therefore practically asymptomatic, even though at times the virus can cross the intestine and be found in the blood. In confirmation of this, molecular tests aimed at detecting the presence of FCoV in the faeces have shown that between 75 and 90% of cats living in boarding or breeding establishments periodically or persistently shed the virus with their faeces even in the absence of obvious symptoms.

This enormous diffusion within the feline population explains, on the one hand, how easy the oro-faecal spreading of the virus is in environments with a high concentration of cats, both by direct infection and, more frequently, by indirect infection through contaminated materials and, on the other hand, how easily FIP tends to appear in such environments.

The presence of FIP is indeed caused by the appearance, within the viral population, of new variants characterised by a greater pathogenicity: coronaviruses in fact possess the largest known RNA genome and are subject to errors in the RNA-dependent RNA polymerase, meaning that sequences that are slightly different than the original ones, known as viral quasispecies, appear at each replication cycle.From this perspective, it is possible for strains endowed with greater pathogenicity to appear, capable of inducing the onset of FIP and characterised by the ability to replicate in macrophages, via which they are transported to various sites of the body. However, the specific mutation responsible for this change in pathogenicity has not yet been identified.

Systemically, the possibility of developing the disease and the type of disease that develops depend on the type of immune response of the host: if the cat has a dominant humoural immunity, it will produce many antibodies that will form the immune complexes responsible for the exudative form of the disease, while if a cell-mediated immunity dominates, the granulomas typical of the non-effusive form will develop. Theoretically, if both a strong cell-mediated immunity and a strong humoural immunity develop, the cat should be capable of counteracting the infection by keeping the virus in a latent state or, theoretically, by eliminating it from its body.

EPIDEMIOLOGY

FIP is most commonly observed among subjects living in multiple-cat environments (catteries, breeding establishments, shelters), in some breeds (e.g. Bengals) or in individual lines within some breeds (Persians), which are at a greater risk of succumbing to FIP. Age is also an important risk factor; indeed, although cats can develop the disease at any age, 50% are under two years of age and over 70% of the cases are in cats under one year old, even if the disease has also been reported in some 17 year-old cats.

Up to 40% of the general feline population in the United Kingdom has been exposed to FCoV, and this number often reaches 90% in breeding establishments and in families with more than one cat in the household. Since FCoVs are highly contagious, once they infect a group of cats, they spread quickly. Nevertheless, while exposure to FCoV is common, the clinical development of FIP is relatively rare. Its incidence is probably <1% in the general feline population and, when the disease occurs, it is usually sporadic. In large groups of cats, where conditions are more favourable for replication and rapid spreading of the virus, up to 10% of the cats may die of FIP. Since only a small percentage of FCoV-infected cats die of FIP, the presence of anti-FCoV antibodies does not mean that the cat might die of infectious peritonitis.

Cats that live in crowded environments, such as in breeding catteries or shelters, are at greater risk of contracting FIP, for several reasons:

• increased possibility of infection with Feline Coronavirus
• increased amount of FCoV
• increase of stress conditions (cats are generally solitary animals)
• increase of the likelihood of concomitant diseases that lower the immune defences.

Stress is a known predisposing condition for the development of FIP; treatment or control of stress is thus an important factor in controlling the disease. In breeding catteries, kittens usually become infected at a young age, when they are 5-6 weeks old, when the maternally derived antibodies (MDA) start to decrease.

The reason for which some cats develop FIP is still not entirely clear. Right after the discovery of FIP in 1963, it was immediately realised that the number of cats with FCoV was higher than the number of cats with FIP, so the presence of two distinct coronaviruses was hypothesised. The hypothesis assumed the existence of an avirulent feline enteric coronavirus (FECV), which differed from the virulent virus responsible for Feline Infectious Peritonitis (FIPV). Today, it has been ascertained that wherever Feline Coronavirus is present, there is the possibility of developing FIP.  

While serological studies have demonstrated the elevated prevalence of FCoV infection, the tests that are currently available are not capable of distinguishing between pathogenic infections (which cause a disease) and non-pathogenic infections (which do not cause a disease). In the first form, fluids accumulate in the abdomen and/or in the chest, while in the second no fluid is present however the cat loses weight, is anorexic, often with hyperthermia, is lymphopaenic and shows different clinical signs depending on the organs affected, which are generally the eyes, liver and brain.

TRANSMISSION

FCOV transmission is mainly indirect, not transplacental, and rarely direct.

The virus is constantly shed through the faeces (sometimes intermittently during the last stages of infection); faeces are therefore the main source of infection and hence litter boxes are the main means of transmission.

In the very early phases of the infection the virus can be detected in the saliva,  but only for a few hours or at most 1-2 days (Addie and Jarrett, 2001);  saliva therefore plays only a marginal role in the transmission of FCoV within the group, even in the case of close contact.

The majority of FCoV-infected cats do not develop FIP but, once infected, the animals shed the virus in the environment through the faeces for 2-3 days, they seroconvert at 18-21 days, they stop shedding the virus after 2-3 to 7 months and, finally, they lose their antibodies. 13% of cats become lifelong carriers, continuing to shed FCoV through the faeces, and maintain a high antibody titre.

In most cases it is the non-mutated coronavirus that is transmitted, and thus the mutation occurs later in the single individual. Very few cases of pathogenic viraemias have been reported in literature.

Predisposed cats are more easily infected following contact with FCOVs present in the faeces of asymptomatic cats.

PATHOGENESIS

The factors which allow  FIP (understood as the disease) to develop within a particular subject are still unknown. One hypothesis is that, while the majority of cats are infected with a virus strain that has scarce possibilities of causing the disease (low pathogenicity virus), slight de novo mutations inherent to the virus that replicates in a particular subject can cause the virus to become more pathogenic (and thus more likely to cause the disease). In particular, the mutation (more specifically a deletion, Vennema et al., 1998), in normally harmless FCoV viruses (sometimes called “feline enteric coronaviruses”), would seem to change the viral tropism from enterocytes to macrophages.

A second theory suggests that the pathogenic strains may be common, however the disease is induced only if other factors are also present, like a high viral load, a particular genetic susceptibility of the host or exposure to factors that impair the host’s immune system. A third theory suggests that cats can succumb to FIP because their immune system is overwhelmed by the development of a viral quasispecies.

The combination of these theories is probably more realistic, meaning that the possibility of developing the clinical form is determined by the status of the immune system, by the nature of the particular viral strain to which the cat is exposed and by the speed with which the virus can replicate within the cat, infecting the macrophages.

The development of potentially pathogenic mutations that cause FIP is more likely to occur when viral replication proceeds at an elevated rate. This explains why FIP develops more commonly in cats with a low immunity status, such as for example in young (<2 years) or very old cats, in cats with immunosuppressive diseases or in stressed subjects (for example, in case of overcrowding).

The exact pathogenesis of FIP is also still not entirely clear; the development of the disease is linked to the appearance of an immune-mediated vasculitis that occurs in around 5-10% of cats infected with Feline Coronavirus. It has been shown that FCoV-infected monocytes adhere to the endothelial cells, they extravasate and differentiate into macrophages, triggering phlebitis and perivasculitis (Kipar et al., 2005). The clinical symptoms are the result of the vascular damage: extensive vascular damage and plasma extravasation favours the formation of effusions in body cavities; the restriction of the infection to more localised sites favours the development of granulomatous lesions.

The first symptoms of FIP appear around 28 days following infection, generally after a stressful event like a change of environment or sterilisation. The effusive form of FIP is the acute form of the disease and it can develop in 4-6 weeks following infection, but also much later if the immune system initially manages to contain it; the non-effusive form, on the other hand, is the chronic form, which can develop from months to years following infection. In the effusive form, the majority of the blood vessels are damaged; in the non-effusive form, the immune response partially manages to contain the infection by “walling in” the infected blood vessels and leading to the formation of pyogranulomas that can become rather voluminous (at abdominal palpation and anatomopathological examination they can be mistaken for tumours).

CLINICAL SIGNS

FIP is one of the most difficult diseases to diagnose in live animals as it can appear with a wide variety of clinical symptoms that reflect the vascular damage present or the distribution of granulomas on the different organs. Common signs of the early stages of FIP, regardless of the evolving clinical form, are a waxing and waning fever, which does not respond to antibiotics, weight loss, anorexia and depression. The distinction between the effusive (exudative) and the dry (pyogranulomatous, non-effusive) form is of clinical value in recognising the presence of the disease; nevertheless, the frequent presence of intermediate forms, that can complicate the disease, are also to be considered as a possibility.

The effusive form is characterised by the presence of effusions in one or more body cavities: the fluid usually tends to accumulate in the abdomen (Fig. 1), but forms with exudative pleurisy (Fig. 2) or bicavitary forms are also common, while exclusively pericardial cases are rare. The main symptom is the presence of an effusion or the presence of clinical alterations attributable to the compression exerted by the effusion itself on the organs of the abdominal cavity (e.g. constipation) and/or thoracic cavity (e.g. dyspnoea). The severity of these clinical signs basically depends on the amount of fluid accumulated within the cavity, which can vary from a few mls to 1-1.5 litres. The signs and symptoms tend to appear quite quickly (in a few days) and the course tends to be hyperacute-acute, with death occurring within a few weeks. Cases with a more protracted course (a few months), or forms that tend to change from effusive to dry, with a course that can reach one year, have been reported. Cases of serositis involving the tunica vaginalis of the testicles, with localised scrotal exudation, and chylous forms of FIP have been reported in literature.

The non-effusive form: when only a small number of vessels are involved in the pathological process, the progression of the disease becomes more chronic and the body attempts to control the vascular lesions with the formation, over a longer period of time, of small or voluminous pyogranulomas on different organs (Fig. 3). The clinical symptoms can often be related directly to the location of these lesions: as an example, the formation of pyogranulomas in the liver leads to jaundice. The course of this non-effusive disorder is known;  it has been proven that the disease develops because of an altered functioning of the cell-mediated immune system (CMI). This second form is much harder to diagnose and, to date, the only diagnostic confirmation comes from histological and/or immunohistological examination of the affected organs.

Cats with the non-effusive form of FIP typically present lethargy, weight loss, anorexia, moderate hyperthermia (39.0-39.5°C, resistant to treatments or recurrent) and a ruffled coat. Some cats may have intraocular lesions, such as uveitis, opacification of the aqueous humour, reddening of the vitreous body, keratic precipitates or thickening of the retinal vessels. FIP is the main cause of inflammatory alterations of the nervous system in the cat, and more than a third of cats with the non-effusive form develop neurological signs, sometimes as the sole initial manifestation. The most common clinical sign is ataxia, followed by nystagmus, vestibular alterations and seizures (Video 1). Incoordination, tremors, hyperaesthesia, behavioural changes, seizures and cranial nerve deficits appear during meningitis. The presence of pyogranulomas in the peripheral nerves or spinal cord may cause lameness, progressive ataxia and tetra-, hemi- or paraparesis.

The majority of cats affected by the dry form of FIP present enlargement of the mesenteric lymph nodes, which may be mistaken for neoplastic masses during abdominal palpation. Common characteristics with the progression of the diseases are the appearance of weakness, weight loss and a cachectic-like state. The dry form tends to appear slowly and to evolve just as slowly, with a course that can last from 2 to 18-24 months. During the terminal stage of the disease the appearance of a wet form, with a hyperacute course, is relatively common.

A particular form, found with a certain frequency in middle-aged cats (4-6 years), is characterised by the appearance of intramural intestinal lesions primarily located in the colon or at the ileocaecocolic junction (Fig.  4). Some cases of this form of FIP, with direct and primary intestinal involvement, have been reported in literature; in a 1996 study (Harvey 1996) involving 156 cases of confirmed FIP, 26 subjects showed a solitary intramural mass at the ileocaecocolic junction or in neighbouring segments. Males and females were equally represented, and the age was between 1 and 3 years in 76% of cases. The clinical manifestations of this form are mainly diarrhoea and vomiting; a palpable abdominal mass, very similar the ones found in intestinal tumours, is often found; in some animals other manifestations may appear, including anorexia, weight loss, hyperthermia, dyspnoea and, finally, pleural or peritoneal effusion. Only one intestinal segment is usually involved, with the length varying between a few centimetres and 15 cm.  At histological examination the intestinal wall generally appears thickened, with granulomatous lesions involving the entire thickness of the organ. Microscopic examination shows the presence of a pyogranulomatous inflammation identical to that of the non-effusive form of FIP, but with lesions located solely in the intestinal area concerned. The pathogenesis of this specific type of alterations can be linked to a partial reaction of the cell-mediated immune system, which initially limits the viral infection to intestinal macrophages, but which subsequently is not capable of eliminating the virus, with development of a chronic, localised and active inflammatory process. It is this inflammatory process which usually induces the development of detectable clinical and pathological alterations.

It is once again worth recalling that the dry, pyogranulomatous form of FIP can nevertheless evolve and affect every organic structure: some atypical forms have therefore been detected in the spleen, testicles, liver and kidneys; some cutaneous manifestations have also been recently reported, with multiple nodular lesions and cutaneous fragility, caused by a pyogranulomatous-necrotising dermal phlebitis.

DIAGNOSIS  

The exudative variant of the disease can be easily diagnosed, as the examination of the fluid produced may be sufficiently diagnostic: the effusion is a modified transudate-nonseptic exudate, of the same consistency of plasma and which coagulates when exposed to air (Fig. 5). A careful analysis of the effusion can lead to a presumptive diagnosis of FIP: the fluid should have a total protein concentration above 3.5 mg/dl (but it is often much higher) and an albumin/globulin ratio below 0.8.

The cytological examination detects the non-abundant presence of nucleated cells (less than 2 x 10_⁹/l), mainly composed of partially degenerated neutrophil granulocytes and macrophages, rare lymphocytes and a granular proteinaceous precipitate background that often makes the morphological characteristics of the cells present difficult to interpret (Fig. 6). The main differential diagnoses are bacterial peritonitis and pleurisy, which is characterised by an effusion containing numerous leukocytes and bacteria.

Protein electrophoresis of the effusion detects a high protein content; the presence of over 32%of gamma globulins (Fig. 7) corresponds to a positive predictive value for FIP of almost 100%. In a clinical setting the diagnostic approach may be hastened by performing the Rivalta test on the effusion

The Rivalta test is a simple and very useful test for diagnosing FIP (Hartmann et al., 2003), characterised by a high sensitivity and specificity (positive predictive value of 86%; negative predictive value of 97%): the test is therefore capable of excluding an exudative FIP in 97% of cases. The test is positive when the effusion is high in protein, fibrin and inflammatory mediators. In some cats with lymphoma or with bacterial peritonitis/pleurisy, the Rivalta test can give a false positive result (Hartmann et al., 2003).

An immunofluorescence test can be used as an additional diagnostic aid, allowing to highlight the virus in the macrophages of the effusion. According to some studies, this test has a positive predictive value (PPV) of 100% (Hartmann 2000).

Measurement of the alpha-1 acid glycoprotein (AGP) concentration can also be useful in the diagnostic approach, as AGP increases greatly (>1500 μg/ml) in the presence FIP, while the value remains normal in the case of myocardial disease or neoplasia, which are the main differential diagnoses. The test is particularly useful when performed on effusions of cats during the acute phase, when all the typical FIP fluid characteristics are often not yet present. The specific characteristics of the effusion should however always be considered, as the AGP concentration may also increase following trauma or surgery or in case of bacterial infection; such case is easily detectable, however, through cytological examination.

To date, no test is capable of providing an accurate diagnosis for the dry forms of FIP. In many cases, a pre-mortem diagnosis can be extremely difficult, if not actually impossible. Histopathology is the only test that can be used for a definitive diagnosis, however in some cases the invasiveness of the bioptic procedure can make it too dangerous to obtain organic material from the live animal.

The subject’s clinical history, the environment in which it lives, the clinical signs present (persistent fever above all others), laboratory alterations, antibody titre and PCR are all factors that can aid in the diagnosis, but still they only allow to formulate a presumptive diagnosis.

Use of laboratory tests

With the exception of histopathology, no diagnostic test allows to make a conclusive diagnosis of FIP. The clinical suspicion may, however, be strongly supported by the simultaneous analysis of several laboratory tests, as specified in more detail below.

Haematological and biochemical examination: over the course of both exudative and non-exudative FIP forms, the haematological alterations are non-specific and vary based on the severity and progression of the disease. Many cats may be affected by neutrophilic leukocytosis; other manifestations may include a mild normocytic-normochromic anaemia and lymphopenia (<1500 cells/mm_³), which can be considered as one of the more specific alterations in FIP. The biochemical profile may show an increase in serum proteins in 50% of cats with effusive FIP and in 70% of patients with the dry form. The increase in proteins is mainly due to a polyclonal elevation of the globulin fraction, however an increase in the alpha-2 globulin fraction is also common (Fig. 7). This increase reflects the presence of acute-phase proteins, which are often altered in the course of FIP.

The serum protein electrophoretic pattern (SPEP) is often indicated as a test for the confirmation of FIP; nevertheless, although SPEP may confirm the polyclonal nature of the increase in globulins, no FIP-specific pattern exists, and in any case any chronic immunological stimulus can cause a similar finding. The peak in the gamma fraction is rarely monoclonal, even in the case of FIP.

The presence of biochemical alterations depends on the localisation of FIP lesions: in the case of hepatic lesions, for example, alterations in cytolysis or in liver function parameters may be found, while in the case of renal lesions, hyperazotaemia or creatininaemia may be detected; given the frequency with which such alterations can be found in cats, neither of the above biochemical alterations can be considered pathognomonic for FIP.

It is worth noticing that among the various proteins one in particular, alpha-1-acid glycoprotein (AGP), increases so steeply in the course of FIP as to acquire diagnostic significance. AGP values above 1.5 mg/dl have a very high sensitivity and diagnostic specificity for FIP.

Search for the Virus: among the tests available to detect the presence of the virus when the infection or the disease is suspected many detect antibodies, while Polymerase Chain Reaction (PCR) allows the detection of the viral RNA.

Tests for the detection of antibodies. Two types of serological tests are basically available: immunofluorescence and ELISA. These assays identify the direct antibodies against the FCoVs. The results of the serological tests play a significant role in the diagnosis of FIP only if correlated to the clinical symptoms, since they detect antibodies aimed at the coronavirus without differentiating between FCoV or FIPV (thus mutated). Seroconversion in cats exposed to coronavirus generally occurs 18-21 days following infection.

Indirect immunofluorescence (IFA) is considered the gold standard technique for evaluating the antibody titre. The advantages of this test are: 1. the presence of a negative control that prevents the detection of a non-specific reaction; 2. the results are expressed as an antibody titre. The titre can be correlated to the disease in progress and have a prognostic value.

FCoV serology is useful when elevated antibody titres are detected; it must always be considered that occasionally cats with the effusive form of FIP have low or non-existent antibody titres, since the majority of the antibodies remains attached to the considerable amount of virus present and are therefore not detectable by the test.

In the dry form, an IFAT titre above 640 may be indicative of the disease, but ONLY in combination with clinical manifestations that are highly indicative of FIP (fever resistant to treatments, hyperproteinaemia, presence of granulomas on several abdominal organs or mesenteric lymphadenopathy, ocular or neurological lesions, altered A/G ratio). A titre below 160 usually allows to exclude a dry form of FIP.

Reverse Transcriptase-Polymerase Chain Reaction test (RT-PCR). This technique allows to amplify a selected part of the viral nucleic acid and to identify the amount of virus in biological samples. The method is extremely sensitive and specific, making it possible to identify very small quantities of viral nucleoproteins, however exactly for this reason many precautions must be taken to prevent contaminations that can generate false positive or false negative results.

The RT-PCR technique can identify coronavirus in cats with FIP that test seronegative, but if performed on blood samples and on tissues it can give false positive results, since FCoV can also be found in the circulation and tissues of healthy cats.

In both the effusive and the non-effusive forms the presence of the virus in the blood of a cat is thus not conclusive for the diagnosis of FIP. In addition, it has been shown that cats with fulminating forms of FIP can be PCR negative. This can occur because, at the time of the test, the cells infected by the virus can still be located in the tissues. For the same reason, a test on a blood sample that is PCR negative does not necessarily indicate that the cat is not hosting the virus in its tissues.

The PCR test is instead reliable if the virus is detected in an effusion, but in this case it should be considered that the diagnosis may also be made using other simpler and less expensive procedures.

Monitoring the shedding of the virus using PCR

A. The use of RT-PCR to detect the presence of the virus in the faeces can be useful to distinguishbetween: 1. an anti-FcoV antibody-positive subject which, after having contracted the infection, has shed the virus and 2. a subject that constantly sheds the virus and which becomes a carrier without ever showing clinical signs of the disease.

To decide on whether a subject is indeed a carrier, it is necessary to turn to specialised labs that can identify the substantial presence of virus in the faeces. The evaluation is performed on four faecal samples collected once a week for 4 consecutive weeks. The patient is considered a healthy carrier, which sheds the virus, if at least three of the tests result positive. RT-PCR makes it possible to monitor the constant shedding of the virus and to prevent the possibility of positivity from external contamination.

B. Monitoring of the salivary excretion of the virus does not allow to obtain the same results, as excretion of the virus in the saliva stops very early compared to faecal emission (Addie, personal observations, 1999).

TREATMENT

Granting that the prognosis for FPI is almost invariably unfavourable, today it is possible to obtain some results in terms of survival rate and improvement in clinical conditions.

Until the recent introduction of recombinant omega interferon of feline origin (rFeIFN-ω), FIP was considered an incurable disease and cats were generally euthanised following the diagnosis. In an initial published study on the use of rFeIFN-ω combined with Prednisolone, 4 cats out of 12 were completely healed and 2 survived for 4 and 5 months, respectively; other studies have given similar results, however the diagnosis was never confirmed in any of these cases (Ishida et al., 2004; Puttner, 2005; Gunn-Moore, 2004).

Although the effusive and non-effusive forms of FIP are not two different diseases, but rather reflect a different degree of the same process, two different treatment protocols for FIP are proposed (Table 1). Based on the author’s experience, in the presence of an exudative FIP the results are almost always discouraging. One case, with a survival time of 200 days, has been reported in literature. The cat appeared “healthy” during the time in which the effusion was absent (Hartmann 2009).

Based on the above considerations, before treating a case of FIP it is always necessary to explain to the cat owner that the purpose of treatment is NOT the HEALING of the patient but the improvement of the clinical conditions. The question still remains on whether it is actually the treatment that prolongs the life of the animal undergoing treatment, or not; there are in fact reports of cats affected by the dry form which, after an initial worsening, tend to improve even for a few months before a fatal end stage. In a double-blind, placebo-controlled trial, no difference was observed between animals treated with glucocorticoids and feline omega-interferon and those treated with only glucocorticoids. In this study, the average survival rate was of only 18 days (Ritz et al., 2007). Although the life expectancy of cats with FIP is short, some cats can live longer, but unfortunately to date the prognostic factors useful for predicting the survival rate of individual cats are not known.

One possible explanation for the prolonged survival rate of some cats might be the genetic difference between cats, which affects the cytokine-mediated inflammatory response (Kiss et al., 2004) or the susceptibility of macrophages (Dewerchin et al., 2005). These genetic differences might be the result of the species and breed predispositions that have been reported for FIP (Robison et al., 1971; Rohrbach et al., 2001; Tammer et al., 1995; O’Brien et al., 1985). Another reason could be that some cats become infected with a less virulent strain of FCoV; indeed, it has been demonstrated that FCoV strains have a different capacity to cause FIP (Mochizuki et al., 1997).

Before treating a cat, it is absolutely essential to make every effort possible to reach a correct diagnosis. Since FIP is an immune-mediated disease, treatment should be aimed at suppressing the inappropriate immune response, usually through the use of high dose corticosteroids; if instead the aetiology of a similar condition were to be infectious, a similar approach could have a disastrous effect (for example in the case of septic peritonitis or pleurisy).

FIP treatment updates are availableon the Internet.

PREVENTION

The route of transmission of FCoV  is mostly indirect: healthy cats come into contact with the faeces of infected cats, generally through the litter box but also through microscopic transmission by means of accessories such as cat litter scoops. Good hygienic practices are therefore the main precautionary measure for controlling FCoV infection. When several cats live together, enough litter boxes should be made available, preferably one per cat. Covered or perhaps self-cleaning litter boxes are to be preferred, in order to prevent the microscopic, infected faecal particles from spreading. A high performance clumping litter is recommended, as well as placing some suitable mats outside the box in order to reduce the scattering of litter, as well as cleaning and disinfecting the boxes with bleach at least once a week.

In veterinary clinics or premises, all cats should be considered as a potential source of FCoV infection and thus routine hygienic measures should always be taken.

If in an environment in which many cats live together a cat should become ill, it is most likely that all the other cats will already have been exposed to FCoV, and hence there is no point in isolating the affected animal. In households in which a single FIP patient has been euthanised, the recommendation is to wait for 2 months before introducing a new cat, so as to ensure the death of the FCoVs present in the environment.

Maternally derived antibodies protect kittens up to 5-6 weeks of age
Kittens born from queens with a positive antibody titre against FCoV are protected by maternally derived antibodies until 5-6 weeks of age. Seropositive pregnant queens should be isolated 1-3 weeks before parturition (3 weeks if they have a concomitant herpesvirus infection). When kittens are 5-6 weeks old, they should be moved to a clean room (in which cats have not been housed for over a week, properly cleaned with a vacuum cleaner and containing a clean and disinfected litter box). The kittens should then be tested starting from when they are 10 weeks old and, if seronegative, placed in contact with the other cats as soon as possible. Kittens with a positive antibody titre should be retested every 4-6 weeks until they become seronegative, and then placed in contact with the other seronegative cats.

Vaccinating cats before the first exposure to Feline Coronavirus
Only one vaccine against FIP is available on the market (not in Italy); many doubts exist as regards its actual efficacy.

Table 1. Recommended therapeutic protocols.

Suggested readings

1. ABCD guidelines on feline infectious peritonitis: Journal of Feline Medicine and Surgery, 2009, 11, 594-604
2. Andrew SE. Feline infectious peritonitis. Vet Clin North Am Small Anim Pract. 2000 Sep;30(5):987-1000.
3. Hoskins J.D.Update on feline coronavirus disease. In: JR August, Consultations in Feline Internal Medicine, III. 1997. Saunders Ed.
4. Kennedy M, Boedeker N, Gibbs P, Kania S.Deletions in the 7a ORF of feline coronavirus associated with an epidemic of feline infectious peritonitis. Vet Microbiol 2001 Aug 8;81(3):227-34
5. Paltrinieri S., Grieco V., Comazzi S..Cammarata Parodi M. Laboratory profiles in cats with different pathological and immunohistochemical findings due to feline infectious peritonitis (FIP). Journal of Feline Medicine and Surgery, 2001, 3(3): 149-159
6. Tammer R, Evensen O, Lutz H, Reinacher M.Immunohistological demonstration of feline infectious peritonitis virus antigen in paraffin-embedded tissues using feline ascites or murine monoclonal antibodies. Vet Immunol Immunopathol. 1995 Nov;49(1-2):177-82.
7. Hartmann K, Binder C, Hirschberger J, et al.Comparison of different tests to diagnose feline infectious peritonitis. J Vet Intern Med 2003; 17: 781–90.
8. Addie, D.D., and Jarrett, J.O.(2001) Use of a reverse-transcriptase polymerase chain reaction for monitoring feline coronavirus shedding by healthy cats.Vet. Rec. 148, 649-653.
9. Addie D.D., Schaap I.A.T, Nicolson L., Jarrett O. (2003) Persistence and transmission of natural type I feline coronavirus infection. J. Gen.Virol. 84 (10), 2735-2744.
10. Ishida T., Shibanai A.,Tanaka S., Uchida K., Mochizuki M.(2004) Recombinant Feline Interferon Therapy of Feline Infectious Peritonitis. J.F.M.S. 6, 107-109.
11. Kipar A , May H, Menger S,Weber M, Leukert W, Reinacher M.2005 Morphologic features and development of granulomatous vasculitis in feline infectious peritonitis.Vet Pathol. 42(3):321-30.
12. Pedersen N.C., Sato R., Foley J.E., Poland A.M.(2004) Common virus infections in cats, before and after being placed in shelters, with emphasis on Feline Enteric Coronavirus. J.F.M.S. 6 83-88
13. Rohrer C, Suter PF, Lutz H. 1993.The diagnosis of feline infectious peritonitis (FIP): a retrospective and prospective study. Kleinterpraxis 38 6 379-389.
14. Shelly, S.M., Scarlett-Kranz J., Blue J.T. 1988 Protein electrophoresis on effusions from cats as a diagnostic test for feline infectious peritonitis. JAAHA 24 495-500
15. Simons F.A.,Vennema H., Rofina J.E., Pol J.M., Horzinek M.C., Rottier P.J., Egberink H.F.(2005) A mRNA PCR for the diagnosis of feline infectious peritonitis J.Virol.Methods 124(1-2):111-6.
16. Vennema H., Poland A., Foley J., Pedersen N.C. (1998) Feline infectious peritonitis viruses arise by mutation from endemic feline enteric coronaviruses.Virology. 243 (1), 150-157.