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Feline infectious peritonitis presenting as a tumour in the abdominal cavity.

This paper describes six cases of feline infectious peritonitis (FIP) in which an abdominal tumour had been suspected clinically. Pathological changes were mainly restricted to the massive enlargement of a mesenteric lymph node due to necrogranulomatous lymphadenitis. FIP was diagnosed on the basis of the immunohistological demonstration of coronavirus antigen in intact macrophages within the necrogranulomatous lesions. In the affected lymph node lymphoid tissue was either almost completely effaced or restricted to follicles composed mainly of variable numbers of blasts. From one to many plasma cells positive for coronavirus-specific antibodies were present in the marginal sinuses or capsules. In addition, necrogranulomas were present in the gut-associated lymphoid tissue of the caecum of one cat, and adjacent to the affected lymph node of another.

Abdominal Neoplasms↗

Prevalence of feline infectious peritonitis in specific cat breeds.

Although known that purebreed cats are more likely to develop feline infectious peritonitis (FIP), previous studies have not examined the prevalence of disease in individual breeds. All cats diagnosed with FIP at a veterinary teaching hospital over a 16-year period were identified. Breed, sex and reproductive status of affected cats were compared to the general cat population and to mixed breed cats evaluated during the same period. As with previous studies sexually intact cats and purebreed cats were significantly more likely to be diagnosed with FIP; males and young cats also had a higher prevalence of disease. Abyssinians, Bengals, Birmans, Himalayans, Ragdolls and Rexes had a significantly higher risk, whereas Burmese, Exotic Shorthairs, Manxes, Persians, Russian Blues and Siamese cats were not at increased risk for development of FIP. Although additional factors doubtlessly influence the relative prevalence of FIP, this study provides additional guidance when prioritizing differentials in ill purebreed cats.

Animals↗

Attempted immunization of cats with feline infectious peritonitis virus propagated at reduced temperatures.

OBJECTIVE: To protect cats by inoculating them intratracheally with feline infectious peritonitis virus (FIPV), followed by a second inoculation with virus propagated at reduced temperatures. ANIMALS: Twelve 12-week-old, specific-pathogen-free kittens. PROCEDURE: Ten to 400,000 plaque-forming units (PFU) of virulent (low passage) FIPV, strain FIPV-1146 were inoculated intratracheally, followed by intranasal inoculation with high-passage FIPV-1146 (10(4) to 10(6) TCID50) on day 133. Cats were allotted to 2 groups and challenge exposed on day 188 by aerosolization of either virulent FIPV-1146 or FIPV-UCD1. RESULTS: Two of the 3 severely affected kittens, given 3 dosages intratracheally, were euthanatized. The third kitten recovered. A serologic response was not detected in cats inoculated with 100 PFU or less and in 1 of 2 cats given 1,000 PFU. Clinical signs of infection were not observed in surviving cats after intranasal inoculation with high-passage FIPV-1146 133 days after the initial dose. All cats seroconverted. Aerosol challenge exposure of all kittens with either virulent FIPV-1146 or FIPV-UCD1 caused no adverse effects except in kittens previously affected after the first inoculation. Residual lesions of FIPV were observed histologically. CONCLUSIONS AND CLINICAL RELEVANCE: There appeared to be a beneficial effect clinically by intratracheal/intranasal inoculation, but not complete protection, as observed histologically.

Administration, Intranasal↗

An uncommon intestinal manifestation of feline infectious peritonitis: 26 cases (1986-1993).

OBJECTIVE: To provide information on an uncommon intestinal manifestation of feline infectious peritonitis (FIP). DESIGN: Retrospective case series. ANIMALS: 26 cats with FIP that had apparently solitary mural intestinal lesions. PROCEDURE: Histologic records of cats for which FIP had been diagnosed by examination of the surgical biopsy specimens were reviewed. Slides of tissue samples from cats identified in the histologic record as having had intestinal lesions were reviewed by the investigators, and records of cats that appeared to have had solitary mural intestinal lesions were included in the study. Information including signalment; history; physical examination findings; results of hematologic, serum biochemical, and serologic analyses; findings at surgery; and results of histologic examination of biopsy specimens were retrieved from these records and supplemented by medical records and additional information obtained from veterinarians submitting the biopsy samples. ABC immunoperoxidase staining was used to detect FIP virus antigen in tissues from cats whose records were selected for inclusion in the study. RESULTS: 26 of 156 cats with a histologic diagnosis of FIP had apparently solitary mural intestinal lesions. Predominant clinical signs were diarrhea and vomiting for 3 months or less before biopsy. All cats had a mass, believed to be a neoplasm, in the colon or ileocecocolic junction. Affected intestine was markedly thickened, nodular, firm, and white, with multifocal pyogranulomas extending throughout the wall of the intestine on histologic examination. Associated lymph nodes were large. Results of immunohistochemical staining were positive for FIP virus. Most cats were euthanatized or died within 9 months of histologic results, many with signs of multisystemic FIP. CLINICAL IMPLICATIONS: The apparent focal nature of intestinal lesions at surgery leads to a different clinical picture than usually seen with FIP, and masses often are believed to be neoplasms. Diagnosis of FIP is important to prevent exposure and infection of other cats. Evaluation of the entire abdominal cavity, biopsy of visible lesions as well as surrounding organs, and postmortem examination are recommended.

Animals↗

Differential in vitro inhibition of feline enteric coronavirus and feline infectious peritonitis virus by actinomycin D.

The growth of feline enteric coronavirus strain 79-1683 in whole feline embryo cells was inhibited by the presence of 1 microgram/ml of actinomycin D in the culture fluid. No virus-specific mRNAs could be detected in such cultures and yields of infectious virus were depressed by > 99%. By contrast, the antigenically related feline infectious peritonitis virus strain 79-1146 was unaffected by the presence of actinomycin D, indicating a fundamental difference between the two feline coronavirus strains in their requirements for host-encoded function(s).

Animals↗

Chemotactic responses of neutrophils in cats with spontaneous feline infectious peritonitis.

The culture supernatant of peritoneal exudate cells (PEC) from cats with effusive feline infectious peritonitis (FIP) was chemotactic for peripheral blood neutrophils (PBN) from healthy cats, magnitude of the chemotactic activity being approximately 10-fold lower than that in zymosan-activated fresh serum of healthy cats (ZAS). The migration profile of PBN from healthy cats was slightly different between the PEC culture supernatant and ZAS. These findings suggest that the chemotactic activity detected in the PEC culture supernatant is distinct from that in ZAS. The chemotactic responses of PBN from FIP cats to ZAS were reduced, as compared with that from healthy controls. In contrast, the neutrophil chemotactic response and sensitivity to the PEC culture supernatant in FIP cats were not remarkably different from those in healthy controls. Furthermore, the chemotactic responsiveness of PEC from FIP cats to ZAS was slightly different from that of PEC to the PEC culture supernatant. These results suggest that neutrophils from FIP cats have altered reactivities against these chemoattractants.

Animals↗

Identification of antigenic sites mediating antibody-dependent enhancement of feline infectious peritonitis virus infectivity.

We have previously demonstrated antibody-dependent enhancement of feline infectious peritonitis virus (FIPV) infection of macrophages using both virus-specific antisera and monoclonal antibodies (MAbs) to the spike (S) protein of FIPV. To increase our understanding of this phenomenon, six representative MAbs from a previously documented group of 12 enhancing MAbs were used to identify epitopes that mediate antibody-dependent enhancement of FIPV infectivity. Analysis of the results of kinetics-based competitive ELISA (K-cELISA) among these six enhancing MAbs grouped the epitopes into two clusters. Because transmissible gastroenteritis virus (TGEV) and FIPV are so closely related antigenically, we also conducted K-cELISA experiments between the FIPV MAbs and TGEV S protein-specific MAbs for which the epitopes had previously been mapped to specific sites on the TGEV S protein. Results of these assays indicated that the two FIPV epitope clusters are homologues of the previously defined TGEV S protein sites A and E/F. In addition, two TGEV S protein-specific MAbs also induced antibody-dependent enhancement of FIPV infection of macrophages. This functional cross-reactivity provides further support for the close antigenic relationship between FIPV and TGEV. Our results provide a preliminary localization of several enhancing epitopes within the amino acid sequence of the FIPV S protein.

Animals↗

The occurrence of feline infectious peritonitis in Denmark.

The clinical and pathologic findings in a case of feline infectious peritonitis (FIP) in a 1-year-old male cat are described. The cat had been sick for about 3 weeks and presented itself clinically with depression, anorexia, dehydration, mild icterus and acites and a temperature of 39.5 degrees C. The sedimentation rate was elevated to 80 mm/30 min. An exploratory laparotomy was performed and ascitic fluid, found to be bacteriologically sterile, was collected. Pathologically, lesions involved both abdominal and thoracic serious membranes and viscera, especially the liver. They ranged from acute, focal necrosis or fibrino-necrotic changes to proliferative inflammation mainly characterized by infiltration with mononuclear cells. An identical disease was produced experimentally by intraperitoneal inoculation of ascitic fluid from the clinical case into 2 healthy cats. This is the first published report of the occurrence of FIP in Scandinavia.

Animals↗

Disseminated intravascular coagulation in experimentally induced feline infectious peritonitis.

Disseminated intravascular coagulation was induced in kittens by intraperitoneal inoculation of feline infectious peritonitis virus (FIPV). Kittens seronegative to FIPV survived significantly (P less than 0.05) longer than those seropositive to FIPV. Pyrexia, anemia, icterus, hyperbilirubinemia, and elevated concentrations of liver-specific enzymes were detected in the inoculated cats. Lesions induced included disseminated fibrinonecrotic and pyogranulomatous inflammation, hepatic necrosis, and widespread phlebitis and thrombosis. Localization of FIP viral antigen and immunoglobulin G was demonstrated in foci of heptic necrosis by immunofluorescence miroscopy. Lymphopenia, thrombocytopenia, hyperfibrinogenemia, and increased quantities of fibrin-fibrinogen degradation products were present in cats after the onset of clinical illness. Depression of factor VII, VIII, IX, X, XI, and XII plasma activities and prolongation of prothrombin and partial thromboplastin times also developed in infected cats. The accelerated onset of clinical disease and mortality in seropositive kittens vs seronegative kittens and the association of virus and antibody in multiple foci of hepatic necrosis suggest an immune-mediated component is involved in the pathogenesis of this disease.

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Epidemiology of feline infectious peritonitis among cats examined at veterinary medical teaching hospitals.

OBJECTIVE: To determine proportions of cats in which feline infectious peritonitis (FIP) was diagnosed on an annual, monthly, and regional basis and identify unique characteristics of cats with FIP. DESIGN: Case-control study. SAMPLE POPULATION: Records of all feline accessions to veterinary medical teaching hospitals (VMTH) recorded in the Veterinary Medical Data Base between January 1986 and December 1995 and of all feline accessions for necropsy or histologic examination at 4 veterinary diagnostic laboratories. PROCEDURE: Proportions of total and new feline accessions for which a diagnosis of FIP was recorded were calculated. To identify characteristics of cats with FIP, cats with FIP were compared with the next cat examined at the same institution (control cats). RESULTS: Approximately 1 of every 200 new feline and 1 of every 300 total feline accessions at VMTH in North America and approximately 1 of every 100 accessions at the diagnostic laboratories represented cats with FIP. Cats with FIP were significantly more likely to be young, purebred, and sexually intact males and significantly less likely to be spayed females and discharged alive than were control cats. The proportion of new accessions for which a diagnosis of FIP was recorded did not vary significantly among years, months, or regions of the country. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that FIP continues to be a clinically important disease in North America and that sexually intact male cats may be at increased risk, and spayed females at reduced risk, for FIP. The high prevalence of FIP and lack of effective treatment emphasizes the importance of preventive programs, especially in catteries.

Age Factors↗

Adverse effects of feline IL-12 during DNA vaccination against feline infectious peritonitis virus.

Cell-mediated immunity is thought to play a decisive role in protecting cats against feline infectious peritonitis (FIP), a progressive and lethal coronavirus disease. In view of the potential of DNA vaccines to induce cell-mediated responses, their efficacy to induce protective immunity in cats was evaluated. The membrane (M) and nucleocapsid (N) proteins were chosen as antigens, because antibodies to the spike (S) protein of FIP virus (FIPV) are known to precipitate pathogenesis. However, vaccination by repeated injections of plasmids encoding these proteins did not protect kittens against challenge infection with FIPV. Also, a prime-boost protocol failed to afford protection, with priming using plasmid DNA and boosting using recombinant vaccinia viruses expressing the same coronavirus proteins. Because of the role of IL-12 in initiating cell-mediated immunity, the effects of co-delivery of plasmids encoding the feline cytokine were studied. Again, IL-12 did not meet expectations - on the contrary, it enhanced susceptibility to FIPV challenge. This study shows that DNA vaccination failed to protect cats against FIP and that IL-12 may yield adverse effects when used as a cytokine adjuvant.

Animals↗

Delayed-type hypersensitivity skin responses associated with feline infectious peritonitis in two cats.

Two cats previously challenge-exposed and seropositive to feline infectious peritonitis virus (FIPV) were evaluated for delayed-type hypersensitivity (DTH) skin responses to intradermal FIPV. Before testing, cat 1 (FIP-resistant) had survived a severe experimental FIPV challenge-exposure and had remained asymptomatic, whereas cat 2 (FIP-susceptible) developed acute fulminant FIP after a considerably smaller virus challenge-exposure. Cat 1 developed a focal thickened plaque at the FIPV-injected skin site at 48 hours after injection. Histological examinations of serial punch biopsies from virus-inoculated skin revealed perivascular and diffuse dermal infiltrations of macrophages, lymphocytes and polymorphonuclear leucocytes which were maximal at 48 to 72 hours after injection. In contrast, cat 2 did not react grossly and showed only very mild dermal infiltrates at 72 hours after injection. The present findings of strong DTH responses to FIPV in a resistant cat and minimal responses in a cat with acute fulminant FIP suggest that certain in vivo cellular immune reactions may be associated with disease resistance.

Animals↗

Antiviral studies of feline infectious peritonitis virus in vitro.

Sixteen compounds were tested for their ability to inhibit the replication in vitro of feline infectious peritonitis virus (FIPV), a coronavirus that causes a lethal, immunologically mediated illness in domestic and exotic cats. Six of the compounds, when incubated with cells and titrations of the virus, were found to reduce the virus titres by 0.401 to 0.833 log10 (P < 0.05), using the cytopathic effect as endpoint. Further inhibition studies were performed to determine the 50 per cent effective dose (ED50) levels for these six compounds. Selectivity indices (50 per cent cytotoxic dose [CD50]/ED50) provided the following order of antiviral activity: pyrazofuin > 6-azauridine > 3-deazaguanosine > hygromycin B > fusidic acid > dipyridamole. Compounds which had no statistically significant effect on FIPV in the same assay were caffeic acid, carbodine, 3-deazauridine, 5-fluoroorotic acid, 5-fluorouracil, D(+)glucosamine, indomethacin, D-penicillamine, rhodamine and taurine.

Animals↗

A mRNA PCR for the diagnosis of feline infectious peritonitis.

A reverse transcriptase polymerase chain reaction (RT-PCR) for the detection of feline coronavirus (FCoV) messenger RNA in peripheral blood mononuclear cells (PBMCs) is described. The assay is evaluated as a diagnostic test for feline infectious peritonitis (FIP). It is based on a well-documented key event in the development of FIP: the replication of virulent FCoV mutants in monocytes/macrophages. To detect most feline coronavirus field strains, the test was designed to amplify subgenomic mRNA of the highly conserved M gene. The test was applied to 1075 feline blood samples (424 from healthy, 651 from sick cats suspected of FIP) and returned 46% of the diseased cats as positive for feline coronavirus mRNA in their peripheral blood cells; of the healthy cats, 5% tested positive. Of a group of 81 animals in which FIP had been confirmed by post-mortem examination, 75 (93%) tested positive, whereas 17 cats with different pathologies (non-FIP cases) all tested negative. In view of the low rate of false-positive results (high specificity) the mRNA RT-PCR may be a valuable addition to the diagnostic arsenal for FIP.

Animals↗

Some aspects of humoral and cellular immunity in naturally occuring feline infectious peritonitis.

Haematology, antibody titers and serum protein electrophoresis from 48 cats (34 effusive and 14 noneffusive forms) affected with feline infectious peritonitis (FIP) were studied and compared with those of 20 healthy cats. In the effusive form, antibody titers and protein electrophoresis in the effusions were analyzed. The distribution of the immune cells and of the virus in FIP lesions were also investigated immunohistochemically with the avidin-biotin complex (ABC) method, using antibodies against the FIP virus (FIPV), myelomonocytic (MAC387) and lymphoid (CD3, CD4 and CD8 for T-cells and IgM and IgG for B-cells) antigens. Seropositive animals (antibody titer>1:100) were present among both the FIP infected cats (73%) and the healthy cats (70%). Cats with effusive FIP had neutrophilic leukocytosis (P>0.05), lymphopenia (P<0.01) and eosinopenia (P<0.001). In both effusive and noneffusive forms decreased albumin/globulin ratio (P<0.001) with hypoalbuminemia (P<0.001), hyperglobulinemia (P<0.001) and increased alpha2- (P<0.05), beta- (P<0.05) and gamma-globulins (P<0.001) were found. Hypergammaglobulinemia was not related to the antibody titers, suggesting the presence of other proteins with gamma-motility (e.g. complement fractions). The electrophoretic pattern of the effusions was always similar to that of the corresponding serum. Antibody titers higher than those of the corresponding serum were often detected in the effusions. Immunohistochemical findings were not related to the antibody titers, but they were related to the histological aspect of the lesions. In cellular foci of FIP lesions many virus-infected macrophages and few lymphocytes, mainly CD4+, were found. Extracellular viral and myelomonocytic antigens were also detectable in the foci with intercellular necrosis. Only few FIPV-infected cells were present at the periphery of the larger necrotic foci: in these lesions MAC387+ cells were mainly neutrophils, with many MAC387 macrophages, probably due to their activated state; a small number of lymphocytes, with an increasing percentage of CD8+ cells was present. Lymphocytes were more abundant when cellular foci and FIP-infected macrophages were centered around neoformed vessels. IgM and IgG exposing B-cells were always few and scattered. In conclusion the simultaneous analysis of body fluids and of the cellular composition of the lesions showed a complex immune status, on which type III and type IV hypersensitivity could coexist.

Animals↗

Virus shedding and immune responses in cats inoculated with cell culture-adapted feline infectious peritonitis virus.

Eight specific pathogen-free cats were inoculated orally or parenterally with a cell culture-adapted strain of feline infectious peritonitis virus (FIPV). Faeces and oropharyngeal swabs were monitored daily for infectious virus by inoculation of feline embryo lung cells. Virus was recovered from both sites for approximately 2 weeks after inoculation, before clinical signs of disease developed. Peripheral blood lymphocytes collected from these cats were tested in an in-vitro blastogenic assay using concanavalin A (con A) and FIPV antigen. All cats showed a profound suppression of the response to con A which only recovered to pre-inoculation levels in 2 cats, one of which survived. These 2 cats also responded to FIPV antigen on the 21st day after infection, the greater response being in the survivor. The other cats, surviving 16-18 days, developed no response to FIPV antigen. Antibody titres, measured by immunofluorescence and by virus neutralization, rose rapidly to very high levels in all cats, regardless of the route of inoculation.

Animals↗

Evaluation of antibody-dependent enhancement of feline infectious peritonitis virus infectivity using in situ hybridization.

Infection of primary macrophages in vitro by feline infectious peritonitis virus (FIPV) was used as a model system to study the kinetics of Fc receptor-mediated antibody-dependent enhancement (FcR-ADE) of virus infectivity at the single cell level. Cells were examined for evidence of viral RNA synthesis at various times points after infection, using 35S-labeled riboprobes and in situ hybridization. At each time point, infection of macrophages with FIPV in the presence of enhancing antiserum was compared to infection with FIPV alone. Both positive- and negative-sense FIPV RNA synthesis began at the same time point after infection in each case. In addition, the level of enhancement was the same from the earliest time of detectable RNA synthesis onward. Therefore, the degree of enhancement appears to be determined at an early point in the infection cycle. These results indicate that Fc-ADE does not induce more rapid viral RNA synthesis compared to infection with FIPV alone. Our results are compared to those of recent work concerning ADE of human immunodeficiency virus (HIV) in the presence of complement.

Animals↗

Intracellular RNAs of the feline infectious peritonitis coronavirus strain 79-1146.

In Felis catus whole foetus D cells infected with feline infectious peritonitis virus (FIPV), strain 79-1146, six virus-specific, poly(A)-containing RNA species of about 20, 9.6, 5.2, 3.8, 2.8 and 1.6 kb were found. By translation in vitro the 3.8 and 2.8 kb RNAs were shown to encode the 25K envelope protein and the 45K nucleocapsid protein, respectively. The partial map of the FIPV genome was compared with genomic maps of porcine, murine and avian coronaviruses. Differences in these maps suggest that transcription units have been lost or gained during coronavirus divergence.

Animals↗