Effusive Feline Infectious Peritonitis Research Articles

Open label clinical trial of orally administered molnupiravir as a first-line treatment for naturally occurring effusive feline infectious peritonitis.

Before the discovery of effective antiviral drugs, feline infectious peritonitis (FIP) was a uniformly fatal disease of cats. Multiple antiviral treatments have been recognized, but optimization of treatment protocols is needed. To evaluate the efficacy of PO molnupiravir (MPV; EIDD-2801) to treat effusive FIP. Ten cats with naturally occurring effusive FIP and 10 historical control cats with effusive FIP treated with PO GS-441524. A single-center, prospective, open-label longitudinal, non-inferiority trial with historical controls. Ten cats with FIP were enrolled and treated with PO MPV (10-15 mg/kg PO q12h) for 84 days. Cats were evaluated at 0, 6, and 16 weeks, and the proportion of cats in clinical remission at 16 weeks was determined. Survival and clinicopathologic features were compared with historical control cats with effusive FIP treated with PO GS-441524. Eight of the 10 cats treated with MPV survived and were in remission at 16 weeks. The 2 non-survivors died in the first 24 hours of treatment. No adverse events that necessitated discontinuation of treatment were observed. Survival of cats treated with PO MPV was non-inferior to historic control cats treated with PO GS-441524 (5/9 [55%] survived), with a difference in survival of 25% (90% confidence interval, -9.3% to 59.3%). Clinicopathologic features associated with FIP normalized during the study period, and no differences in clinicopathologic data at each study time point were observed when comparing cats treated with MPV and GS-441524. Molnupiravir is an effective antiviral treatment for effusive FIP.

SERUM AND ASCITES FLUID BIOCHEMICAL PROFILEOF EFFUSIVE-TYPE FELINE INFECTIOUS PERITONITIS

Feline Infectious Peritonitis (FIP) is a fatal disease occurring in cats worldwide caused by Feline Coronavirus. Antemortem diagnosis of FIP is difficult due to non-specific clinical and laboratory signs. Rapid and reliable diagnosis is essential for prognostic purposes. The study was aimed to evaluate the serum biochemical profile and ascites of cats with effusive FIP. This study used five cats suspected of effusive FIP as a samples. Diagnosis was based on clinical examination, Rivalta and rapid test of FIP antibodies to ascites samples. Blood serum and ascites fluid were collected for examination of total protein, albumin, globulin and albumin/globulin (A/G) ratio. Clinical examination results showed that 5/5 (100%) cats had ascites. Rivalta test on ascites sample was positive for exudate and antibody rapid test was positive for FIP. The biochemical test showed an average total serum protein and ascites fluid of 7.14 ± 1.36 g/dL and 6.12 ± 0.33 g/dL (P<0.05); hypoalbuminemia was found in serum samples with an average of 1.94 ± 0.33 g/dL and ascites fluid albumin of 1.69 ± 0.32 g/dL (P<0.05), serum globulin had an average of 5.06 ± 1.32 g/dL and ascites globulin of 4.80 ± 0.88 g/dL (P>0.05). All cats had a low mean A/G ratio of 0.37 ± 0.36 in serum and 0.34 ± 0.01 in ascites (P>0.05). Concluded that the biochemical profile of serum and ascites in effusive FIP included normal total protein, hypoalbuminemia, normal serum globulin and decreased A/G ratio. Moreover, significant statistical discrepancy in serum and ascites biochemical profiles only occurred in total protein and albumin, but not in globulin and A/G ratio.

Intestinal injury and vasculitis biomarkers in cats with feline enteric coronavirus and effusive feline infectious peritonitis.

To investigate intestinal injury, repair and vasculitis biomarkers that may illuminate the progression and/or pathogenesis of feline infectious peritonitis (FIP) or feline enteric coronavirus (FECV) infection. A total of 40 cats with effusive FIP (30 with abdominal effusion, AE group; 10 with thoracic effusion, TE group) and 10 asymptomatic but FECV positive cats (FECV group), all were confirmed by reverse transcription polymerase chain reaction either in faeces or effusion samples. Physical examinations and effusion tests were performed. Trefoil factor-3 (TFF-3), intestinal alkaline phosphatase (IAP), intestinal fatty acid binding protein (I-FABP), myeloperoxidase-anti-neutrophilic cytoplasmic antibody (MPO-ANCA) and proteinase 3-ANCA (PR3-ANCA) concentrations were measured both in serum and effusion samples. Rectal temperature and respiratory rate were highest in the TE group (p<0.000). Effusion white blood cell count was higher in the AE group than TE group (p<0.042). Serum TFF-3, IAP and I-FABP concentrations were higher in cats with effusive FIP than the cats with FECV (p<0.05). Compared with the AE group, TE group had lower effusion MPO-ANCA (p<0.036), higher IAP (p<0.050) and higher TFF-3 (p<0.016) concentrations. Markers of intestinal and epithelial surface injury were higher in cats with effusive FIP than those with FECV. Compared to cats with abdominal effusions, markers of apoptosis inhibition and immunostimulation to the injured epithelium were more potent in cats with thoracic effusion, suggesting the possibility of a poorer prognosis or more advanced disease in these patients.

Efficacy of Oral Remdesivir Compared to GS-441524 for Treatment of Cats with Naturally Occurring Effusive Feline Infectious Peritonitis: A Blinded, Non-Inferiority Study.

Nucleoside analogs GS-441524 and remdesivir (GS-5734) are effective in treating cats with feline infectious peritonitis (FIP). However, no studies have compared the efficacy between antiviral medications. The objective of this study was to evaluate the efficacy of orally administered GS-442514 (12.5-15 mg/kg) compared to orally administered remdesivir (25-30 mg/kg) in a double-blinded non-inferiority trial. Eighteen cats with effusive FIP were prospectively enrolled and randomly assigned to receive either GS-442514 or remdesivir. Cats were treated daily for 12 weeks and evaluated at week 0, 12, and 16. Survival and disease remission at week 16 were compared between groups. Five of 9 (55%) cats treated GS-441524 and 7/9 (77%) cats treated with remdesivir survived, with no difference in survival rate (p = 0.2). Remdesivir fulfilled the criteria for non-inferiority with a difference in survival of 22% (90% CI; -13.5-57.5%). Three of the 18 cats died within 48 h of enrollment. Excluding these cats, 5/6 (83%) of the cats treated with GS-441524 and 7/9 (77%) of the cats treated with remdesivir survived. These findings suggest that both orally administered GS-441524 and remdesivir are safe and effective anti-viral medications for the treatment of effusive FIP. Further optimization of the first 48 h of treatment is needed.

Retrospective Survival Analysis of Cats with Feline Infectious Peritonitis Treated with Polyprenyl Immunostimulant That Survived over 365 Days.

Feline infectious peritonitis (FIP) remains a major diagnostic and treatment challenge in feline medicine. An ineffective immune response is an important component of FIP pathophysiology; hence treatment with an immune stimulant such as Polyprenyl Immunostimulant™ (PI), which enhances cell-mediated immunity by upregulating the innate immune response via Toll-like receptors, is a rational approach. Records of cats with FIP treated with PI orally for over 365 days were retrospectively studied. Of these cats (n = 174), records were obtained for n = 103 cats with appropriate clinical signs and clinical pathology. Of these, n = 29 had FIP confirmed by immunohistochemistry (IHC) or reverse transcription polymerase-chain-reaction (RT-PCR). Most of the cats (25/29; 86%) had non-effusive FIP, and only 4/29 cats (14%) had effusive FIP. The mean survival time (MST) was 2927 days (eight years); with 55% of the cats (16/29) still being alive at the time data collection, and 45% (13/29) having died. A persistently low hematocrit plus low albumin:globulin (A:G) ratio, despite treatment, was a negative prognostic indicator. It took a mean of ~182 days and ~375 days, respectively, for anemia and low A:G ratio to resolve in the cats that presented with these laboratory changes. This study shows that PI is beneficial in the treatment of FIP, and more studies are needed to establish the best protocols of use.

Intestinal Damage and Vasculitis Biomarkers in Cats with Feline Enteric Coronavirus and Effusive Feline Infectious Peritonitis

Intestinal Damage and Vasculitis Biomarkers in Cats with Feline Enteric Coronavirus and Effusive Feline Infectious Peritonitis

Evaluation of the Usefulness of Serum Feline Alpha 1-acid Glycoprotein Test for Diagnosis of Effusive Feline Infectious Peritonitis

Evaluation of the Usefulness of Serum Feline Alpha 1-acid Glycoprotein Test for Diagnosis of Effusive Feline Infectious Peritonitis

Therapeutic Effects of Mutian® Xraphconn on 141 Client-Owned Cats with Feline Infectious Peritonitis Predicted by Total Bilirubin Levels.

Feline infectious peritonitis (FIP) is a fatal disease caused by feline coronavirus or its variant, referred to as the FIP virus. Recently, favorable treatment outcomes of the anti-viral drug Mutian® Xraphconn (Mutian X) were noted in cats with FIP. Thus, the therapeutic efficacy of Mutian X in cats with FIP must be explored, although the predictors of therapeutic success remain unknown. In the present study, we administered Mutian X to 141 pet cats with effusive FIP following initial veterinarian examinations. Of these, 116 cats survived but the remaining 25 died during treatment. Pre-treatment signalment, viral gene expression, and representative laboratory parameters for routine FIP diagnosis (i.e., hematocrit, albumin-to-globulin ratio, total bilirubin, serum amyloid-A, and α1-acid glycoprotein) were statistically compared between the survivor and non-survivor groups. The majority of these parameters, including hematocrit, albumin-to-globulin ratio, serum amyloid-A, α1-acid glycoprotein, and viral gene expression, were comparable between the two groups. Interestingly, however, total bilirubin levels in the survivor group were significantly lower than those in the non-survivor group (p < 0.0001). Furthermore, in almost all surviving cats with effusive FIP (96.6%, 28/29), the pre-treatment total bilirubin levels were below 0.5 mg/dL; however, the survival rate decreased drastically (14.3%, 1/7) when the pre-treatment total bilirubin levels exceeded 4.0 mg/dL. Thus, circulating total bilirubin levels may act as a prognostic risk factor for severe FIP and may serve as the predictor of the therapeutic efficacy of Mutian X against this fatal disease.

A comparative study of techniques used for the diagnosis of effusive feline infectious peritonitis

Feline infectious peritonitis (FIP) is a fatal disease caused by feline infectious peritonitis virus (FIPV). At present, neither a licensed treatment nor an accurate ante-mortem diagnosis are available. In the present study, three available tests were evaluated for their diagnostic power on effusion samples. High feline coronavirus antibody titers, measured with an immunoperoxidase monolayer assay (IPMA), were correlated with FIP but its low specificity precluded a reliable diagnosis. The in-house 5’ reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) provided a much better specificity and high sensitivity. Given the low sensitivity of immunofluorescence staining (IF) of effusive cells, the RT-qPCR alone or in combination with IPMA represents a good alternative for IF. In the majority of the effusion samples from FIP positive animals, Sanger sequencing of the open reading frame encoding the spike protein (ORF S) revealed not only mutations that were previously associated with FIP (M1058L, S1060A, I1106T and D1108Y/E/G) but also two new, closely related mutations (T1112S/N).

Characteristic clinical signs and blood parameters in cats with Feline Infectious Peritonitis

Feline infectious peritonitis (FIP) is a common disease with high mortality rates in cats that occurs as either an effusive or non-effusive form. Confirmation of FIP in clinical practice is difficult and remains a challenge because there are no pathognomonic lesions or specific diagnostic indicators. Thus, clinical features were investigated to evaluate the hematological and biochemical parameters between FIP and non-FIP cats. A sample of 50 blood donor cats and 50 effusive FIP cats presented at the Kasetsart University Veterinary Teaching Hospital were divided into non-FIP and FIP groups, respectively. The average age of FIP cats was significantly (p < 0.05) lower than fornon-FIP cats. The results indicated that cat breeds correlated with FIP (p < 0.05). Significantresults concerning hematological and biochemical findings revealed values of packed cell volume (PCV), red blood cells (RBC), hemoglobin (HGB), mean corpuscular volume (MCV), lymphocytes, eosinophils, blood urea nitrogen (BUN), creatinine, alanine aminotransferase (ALT), albumin and albumin:globulin (A:G) ratio in the FIP group were lower and numbers of white blood cells (WBC), segmented neutrophils, plasma protein (PP), total protein and globulin in the FIP group were higher than in the non-FIP group (p < 0.05). In conclusion, anemia, neutrophilia, lymphopenia, hypoalbuminemia, hyperglobulinemia and a low A:G ratio presented as hematological and biochemical changes in FIP cats. Blood profiling could be a useful approach for FIP diagnosis to assist clinicians to determine and evaluate the correct treatment, prognosis and progressive monitoring.

Discrepancies between feline coronavirus antibody and nucleic acid detection in effusions of cats with suspected feline infectious peritonitis

Intra-vitam diagnosis of feline infectious peritonitis (FIP) is a challenge for veterinary diagnosticians, since there are no highly specific and sensitive assays currently available. With the aim to contribute to fill this diagnostic gap, a total of 61 effusions from cats with suspected effusive FIP were collected intra-vitam for detection of feline coronavirus (FCoV) antibodies and RNA by means of indirect immunofluorescence (IIF) assay and real-time RT-PCR (qRT-PCR), respectively. In 5 effusions there was no evidence for either FCoV RNA or antibodies, 51 and 52 specimens tested positive by IIF and qRT-PCR, respectively, although antibody titres≥1:1600, which are considered highly suggestive of FIP, were detected only in 37 effusions. Three samples with high antibody levels tested negative by qRT-PCR, whereas 18 qRT-PCR positive effusions contained no or low-titre antibodies. qRT-PCR positive samples with low antibody titres mostly contained low FCoV RNA loads, although the highest antibody titres were detected in effusions with CT values>30. In conclusion, combining the two methods, i.e., antibody and RNA detection would help improving the intra-vitam diagnosis of effusive FIP.

Clinical and laboratory features of cats with feline infectious peritonitis--a retrospective study of 231 confirmed cases (2000-2010).

The objectives of this study were to review signalment, clinical signs and laboratory features in a large number of naturally occurring cases of feline infectious peritonitis (FIP), and to evaluate potential changes in diagnostic criteria for FIP and compare findings in cats with and without effusion. The medical records of 231 cats with confirmed FIP that presented to the Clinic of Small Animal Medicine of the Ludwig-Maximilian University of Munich, Germany, were reviewed for signalment, history, and clinical and laboratory parameters. Age, sex and breed distribution of the cats were compared with the clinic population. Male sex and young age were significantly correlated with FIP. Neutering status was not associated with FIP. No breed predisposition was observed and the majority of cats presented were domestic shorthair and mixed breed. Microcytosis of peripheral erythrocytes was found in 35.1% of cats, of which 42.4% did not have concurrent anaemia. Band neutrophilia was documented in 44.3% (81/183), of which 35.8% did not have mature neutrophilia. Lymphopenia, observed significantly more often with effusion, was documented in only 26.8% of cats without effusion. Hyperbilirubinaemia also occurred significantly more often in cats with vs without effusion. While serum total protein was increased in only 17.5% of cats, hyperglobulinaemia was documented in 89.1%. Nearly 85.0% of cats had an albumin-to-globulin (A:G) ratio <0.8, while 67.8% had an A:G ratio <0.6. Microcytosis was common and can increase suspicion of FIP in the presence of other typical clinical and laboratory abnormalities. The low prevalence of lymphopenia in cats without effusion suggests that this is not a useful parameter in non-effusive FIP. The frequent occurrence of a left shift in the absence of a mature neutrophilia complicates the differentiation of effusive FIP and septic peritonitis. Globulins and A:G ratio were of higher diagnostic value than hyperproteinaemia.

Treatment of a case of feline infectious peritonitis with cyclosporin A

Feline infectious peritonitis is a fatal viral disease which is currently incurable by drugs. Also, there are no effective vaccines. Cyclosporin A (CsA) was recently shown in vitro to exert...

Diagnostic utility of a direct immunofluorescence test to detect feline coronavirus antigen in macrophages in effusive feline infectious peritonitis

The antemortem diagnosis of feline infectious peritonitis (FIP) remains challenging in clinical practice, since current testing methods have suboptimal diagnostic accuracy. Immunohistochemical testing of biopsy specimens and postmortem examination are the standard diagnostic methods, although direct immunofluorescence (DIF) testing to detect feline coronavirus in macrophages in effusion specimens has been reported to have 100% specificity and has been recommended as an antemortem confirmatory test. The aim of this study was to compare the results of DIF testing in antemortem feline effusions with postmortem results using field samples. Effusion specimens were collected antemortem from 17 cats and tested by DIF, followed by postmortem examination. Histopathological examination of specimens collected at postmortem confirmed FIP in 10/17 cases and ruled out FIP out in 7/17 cases. Antemortem DIF testing was positive in all 10 cases confirmed as FIP at postmortem examination. In the seven cats where FIP was ruled out at postmortem examination, DIF was negative in five cases and positive in the remaining two cases. The calculated sensitivity of DIF testing was 100% and the specificity was 71.4%. Duplicate effusion specimens from eight cats that were initially DIF positive were stored refrigerated (4°C) or at room temperature (22–25°C) and subjected to serial DIF testing to determine the duration of positive results. DIF-positive specimens stored at both temperatures retained their positive status for at least 2days.

Clinicopathological findings and disease staging of feline infectious peritonitis: 51 cases from 2003 to 2009 in Taiwan

Fifty-one cats histopathologically confirmed to have been naturally infected by feline infectious peritonitis (FIP), were collected to analyse the clinical and laboratory findings and to characterise disease staging. Effusive FIP was found in 33 cats, non-effusive FIP in 12 cats, and mixed-type in six cats. Highly significant decreases in haematocrit and albumin levels and an increase in total bilirubin level were noted in both effusive and non-effusive FIP, at first presentation and before death. In serial blood examinations of the effusive group, anaemia and increases in bilirubin and aspartate aminotransferase (AST) were observed from 2 weeks to 0–3 days before death. The packed cell volume, bilirubin, AST, potassium, and sodium levels were established to predict disease staging and survival time. Cumulative points ranging from 0 to 4, 5 to 11 and excess of 12, indicate that the cat can survive for at least 2 weeks, less than 2 weeks and less than 3 days, respectively.

Detection of feline coronavirus antibody, feline immunodeficiency virus antibody, and feline leukemia virus antigen in ascites from cats with effusive feline infectious peritonitis.

To investigate the usefulness of ascites as a material for viral tests in cats with effusive feline infectious peritonitis (FIP), we attempted to detect anti-feline coronavirus antibody, anti-feline immunodeficiency virus antibody, and feline leukemia virus antigen in ascites from 88 cats clinically suspected with effusive FIP. In each of these three viral tests, all cats positive for serum antibody/antigen were also positive for ascitic antibody/antigen, while cats negative for serum antibody/antigen were also negative for ascitic antibody/antigen. This finding indicates that ascites is useful for these viral tests.

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 α 2- ( P<0.05), β- ( P<0.05) and γ-globulins ( P<0.001) were found. Hypergammaglobulinemia was not related to the antibody titers, suggesting the presence of other proteins with γ-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.

Development of a nested PCR assay for detection of feline infectious peritonitis virus in clinical specimens

A diagnostic test for feline infectious peritonitis virus (FIPV) infection based on a nested PCR (nPCR) assay was developed and tested with FIPV, feline enteric coronavirus (FECV), canine coronavirus (CCV), and transmissible gastroenteritis virus (TGEV) and clinical fluid samples from cats with effusive feline infectious peritonitis (FIP). The target sequence for the assay is in the S1 region of the peplomer protein E2 gene. A vaccine strain of FIPV and two wild-type FIPV strains tested positive, but FECV, TGEV, and CCV tested negative. Preliminary tests with 12 cats with clinical evidence of effusive FIP and 11 cats with an illness associated with effusions, but attributed to other causes, were performed. Eleven of the 12 cats with effusive FIP tested positive, while 1 was negative. Ten of the 11 cats ill from other causes tested negative, while 1 was positive. On the basis of clinical laboratory and histopathologic criteria, the preliminary sensitivity and specificity of the assay were 91.6 and 94%, respectively.

Morbidity, Mortality and Coronavirus Antigen in Previously Coronavirus Free Kittens Placed in Two Catteries with Feline Infectious Peritonitis

Serologically coronavirus free kittens were placed in 2 catteries with a history of feline infectious peritonitis (FIP), each cattery representing 1 of the 2 different predominant clinical characteristics of FIP--effusive and granulomatous. The kittens were clinically observed for 100 days. A 100% morbidity and a 90% mortality was observed. The first signs were observed after 14 and 27 days respectively. The clinical pattern of the disease was similar in all kittens and showed a pattern of recurrent periods of conjunctivitis, upper respiratory and gastrointestinal signs. Once developed, wasting and signs of CNS disturbances were consistent. The "effusive strain" had a 2 weeks earlier onset of signs and death, and a 40% outcome of effusive FIP. Mean survival times during the observation period were 57 +/- 26 and 57 +/- 16 (mean +/- SD in days), respectively. The death rates were similar in both groups. Feline coronavirus (FCoV) antigen was immunohistochemically detected using indirect immunofluorescence and was present in all kittens and in 93% of the 5 investigated organs (lung, liver, spleen, kidney, and mesenteric lymph node).

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.