Effect of feline interferon-omega on the survival time and quality of life of cats with feline infectious peritonitis

BACKGROUND: There is no therapy with proven efficacy to treat cats with feline infectious peritonitis (FIP). HYPOTHESIS: Feline interferon-omega (FeIFN-omega) prolongs survival time and increases quality of life in cats with FIP. ANIMALS: Thirty-seven privately owned cats were subjects of this study. METHODS: The study was performed as a placebo-controlled double-blind trial. Feline infectious peritonitis was confirmed by histology or immunostaining of feline coronavirus (FCoV) antigen in effusion or tissue macrophages or both. The cats were randomly selected for treatment with either FeIFN-omega or a placebo. All cats received adjunctive treatment with glucocorticoids and antibiotics and passive immunization with Feliserin. RESULTS: There was no statistically significant difference in the survival time of cats treated with FeIFN-omega versus placebo or in any other variable evaluated (with the exception of the lymphocyte count). The cats survived between 3 and 200 days (median, 9 days). There was only 1 long-term survivor (> 3 months), and the cat was in the FeIFN-omega group. CONCLUSION AND CLINICAL RELEVANCE: No effect of FeIFN-omega on survival time or quality of life could be demonstrated in this study.     

Treatment of cats with feline infectious peritonitis

Feline infectious peritonitis (FIP) infection resulting in clinical signs is invariably fatal despite clinical intervention. As FIP is an immune-mediated disease, treatment is mainly aimed at controlling the immune response triggered by the infection with the feline coronavirus (FCoV). Immune suppressive drugs such as prednisone or cyclophosphamide may slow disease progression but do not produce a cure. In nearly every published case report of attempted therapy for clinical FIP, glucocorticoids have been used; there are, however, no controlled studies that evaluate the effect of glucocorticoids as a therapy for FIP. Some veterinarians prescribe immune modulators to treat cats with FIP with no documented controlled evidence of efficacy. It has been suggested that these agents may benefit infected animals by restoring compromised immune function, thereby allowing the patient to control viral burden and recover from clinical signs. However, a non-specific stimulation of the immune system may be contraindicated as clinical signs develop and progress as a result of an immune-mediated response to the mutated FCoV.     

Epigenetic transmission of feline infectious peritonitis

Feline Infectious Peritonitis (F.I.P.) was diagnosed in the kittens of two successive litters born to a female presumed also infected.At the same time, the two fathers and the other subjects of the cattery remained asymptomatic of F.I.P.The clinical observations, supported by electrophoretic data, suggest the possibility of a direct transmission of the disease by the mother to her offspring, either by the transplacentary pathway (epigenetic transmission) or via the milk.     

Interferon-gamma in the serum and effusions of cats with feline coronavirus infection

The aim of this study was to quantify and compare interferon-γ (IFN-γ) concentrations in the serum of clinically normal cats infected with feline coronavirus (FCoV) with its concentration in the sera and effusions of cats with feline infectious peritonitis (FIP), a disease associated with infection with a mutated form of FCoV.Clinically normal FCoV-infected cats living in catteries with a high prevalence of FIP had the highest serum IFN-γ concentrations. The serum concentration of IFN-γ was not significantly different in cats with FIP compared with clinically normal FCoV-infected animals living in catteries with a low prevalence of the disease. Moreover, the concentration of IFN-γ was significantly higher in the effusions than in the serum of cats with FIP, probably due to IFN-γ production within lesions. These findings support the hypothesis that there is a strong, ‘systemic’ cell mediated immune response in clinically normal, FCoV-infected cats and that a similar process, albeit at a tissue level, is involved in the pathogenesis of FIP.     

Performances of different diagnostic tests for feline infectious peritonitis in challenging clinical cases

Objectives : Feline infectious peritonitis (FIP) can be difficult to diagnose. Histopathology is considered the gold standard test but immunohistochemistry (IHC) is mandatory to confirm/exclude the disease. This study aimed to assess the performances of tests carried out in vivo or at postmortem examination in challenging cases in which FIP was confirmed or excluded based on IHC or on adequate follow‐up. Methods : Twelve cases (four without FIP, eight with FIP) were retrospectively studied. Clinical findings, serum protein electrophoresis (SPE), analysis of the effusions (AE), antifeline coronavirus serology, serum concentration of α1‐acid glycoprotein (AGP) and histopathology were classified as consistent, doubtful or non‐consistent with FIP. Sensitivity, specificity and concordance (κ) with the final diagnosis were calculated. Results : Concordance was absent for serology (κ=?0·08) and AE (κ=?0·52), poor for histopathology (κ=0·09), fair for SPE (κ=0·25) and perfect for AGP (κ=1·00). Sensitivity was high for AGP (100%) and low for AE (50%), SPE (37·5%) and histopathology (37·5%). Specificity was high for AGP or histopathology (100%) and low for SPE (50%) and AE (0%). Clinical Significance : IHC must always be performed to confirm FIP. If this is not possible, when histopathology is controversial, elevated AGP concentrations may support the diagnosis of FIP.     

Relationship between rate of infection and markers of inflammation/immunity in Holy Birman cats with feline coronavirus

The aim of this study was to assess whether Holy Birman cats (HB) have a peculiar immune profile and a higher rate of infection by feline coronaviruses (FCoV). Leucocyte and lymphocyte subsets, antibody titers, α₁-acid glycoprotein (AGP), globulin fractions, IL-4, IL-12 and IFN-γ in blood and fecal FCoV excretion were determined in HB (n = 75) and in cats from other breeds (n = 94). Significantly higher CD4/CD8 ratio, IFN-γ concentration and IL12/IL4 ratio and significantly lower IL-4 concentration and proportion of shedders were found in HB than in other breeds. No other differences were found. In conclusion, this study did not provide evidence of peculiar immune profiles in HB, except for a prevalent Th1 profile, that may explain why in our caseload the rate of shedders was lower in HB than in other breeds.     

Antibody-mediated enhancement of disease in feline infectious peritonitis: Comparisons with dengue hemorrhagic fever

Non-immune kittens passively immunized with feline serum containing high-titered antibodies reactive with feline infectious peritonitis virus (FIPV) developed a more rapid disease after FIPV challenge than did kittens pretreated with FIPV antibody-negative serum. Antibody-sensitized, FIPV challenged—kittens developed earlier clinical signs (including pyrexia, icterus, and thrombocytopenia) and died more rapidly than did non-sensitized, FIPV-challenged kittens. Mean survival time in sensitized kittens was significantly (P < 0.05) reduced compared to non-sensitized kittens (mean ± SEM, 10.0 ± 0.6 days vs. 28.8 ± 8.3 days, respectively). Lesions induced included fibrinous peritonitis, disseminated pyogranulomatous inflammation and necrotizing phlebitis and periphlebitis. FIPV antigen, immunoglobulin G, complement (C3) and fibrinogen were demonstrated in lesions by immunofluorescence microscopy.The pathogenesis of dengue hemorrhagic fever (DHF) in persons bears striking resemblance to that of FIP in experimental kittens. In both FIP and DHF, non-neutralizing antibody may promote acute disease by enhancement of virus infection in mononuclear phagocytes or by formation of immune complexes, activation of complement and secondary vascular disturbances.     

A discrete-event computer model of feline herpes virus within cat populations

The purpose of this work was to study the epidemiology of feline herpes virus (FHV), which causes a respiratory disease within natural populations of domestic cats. A stochastic model was constructed using discrete-events simulation. Two habitats (rural vs. urban) were simulated, featuring different demographic, spatial and social patterns. The evolution of immunity in individuals was reproduced, allowing for the random recrudescence of latent infections (influenced by environment and reproduction). Hypotheses concerning the circulation of FHV were examined regarding the role of host density and the possibility of reinfection of host. Uncertainty analyses were performed on the basis of replicated Monte Carlo sampling. The results were in good agreement with serologic data from a long-term study conducted on five populations in France. The model satisfactorily reproduced the variability of natural immunity, and the epidemic features observed. The simulations have shown that FHV can persist in small populations (because of its capacity of reactivation leading to epidemics). However, the impact on demography was not dramatic. The most important parameters in determining change in epidemiology of FHV were: transmission rate corresponding to ‘friendly’ contacts, and the recrudescence rate of FHV. However, an interaction between these two parameters did not allow estimation of their values.     

Characterisation of canine parvovirus strains isolated from cats with feline panleukopenia

Unlike the original canine parvovirus type 2 (CPV-2), CPV-2 variants have gained the ability to replicate in vivo in cats but there is limited information on the disease patterns induced by these variants in the feline host. During 2008, two distinct cases of parvoviral infection were diagnosed in our laboratories. A CPV-2a variant was identified in a 3-month-old Persian kitten displaying clinical sign of feline panleukopenia (FPL) (acute gastroenteritis and marked leukopenia) and oral ulcerations, that died eight days after the onset of the disease. Two pups living in the same pet shop as the cat were found to shed a CPV-2a strain genetically identical to the feline virus and were likely the source of infection. Also, non-fatal infection by a CPV-2c strain occurred in a 2.5-month-old European shorthair kitten displaying non-haemorrhagic diarrhoea and normal white blood cell counts. By sequence analysis of the major capsid protein (VP2) gene, the feline CPV-2c strain showed 100% identity to a recent canine type-2c isolate. Both kittens had been administered multivalent vaccines against common feline pathogens including FPL virus. Whether and to which extent the FPL vaccines can protect cats adequately from the antigenic variants of CPV-2 should be assessed.     

成都地区猫传性腹膜炎病毒ORF3、7b以及S基因七肽重复区1序列的分析

猫传性腹膜炎(FIP)是由猫冠状病毒引起的猫科常见致死性传染病。为分析成都地区猫传性腹膜炎病毒(FIPV)部分基因的序列特征,本研究从11只FIP患猫的腹水中提取总RNA,采用普通PCR或套式PCR对FIPV的非结构蛋白基因ORF3 (3a、3b和3c)、7b以及S基因七肽重复区1 (HR1)序列进行PCR扩增并测序。结果显示:检测到FIRV的上述几个基因均呈遗传多样性,序列存在很大的个体间差异。3a和3b基因主要表现为氨基酸突变,3c基因在约89%的样品中存在截短。7b基因有7个位点的氨基酸被完全替换。S基因HR1序列融合肽的1045位甲硫氨酸被亮氨酸替换,其下游的1057位丝氨酸被丙氨酸替换。遗传进化树显示,本实验扩增的FIRV 7b及S基因HR1序列与GenBank中国外FIPV相应基因序列亲缘性较高。推测3c基因的截短和/或某些氨基酸的替换的共同作用与病毒的致病性有关。本研究结果为FIP的临床确诊提供了分子诊断依据,增加了临床诊断结果的可靠性。     

Expression in Escherichia coli and purification of the functional feline granulocyte colony-stimulating factor

Feline granulocyte colony-stimulating factor (G-CSF) with an N-terminal histidine hexamer tag was expressed as inclusion bodies in E. coli. The G-CSF solubilized in 6 M guanidine solution was absorbed onto a Ni-NTA column and, after washing with decreasing concentrations of guanidine, eluted with imidazole in a soluble and apparently pure form. The activity of the recombinant feline G-CSF was 3×10⁶ U/mg protein, as assayed by its stimulatory effect on NFS-60 cell proliferation. When a low level of purified feline G-CSF was administered once a day for two successive days to cats, the number of neutrophil increased 4-fold while the levels of other blood cell types remained virtually unchanged. Daily administration of G-CSF for a total of 11 days led to a more than 10-fold increase in neutrophils, an 8-fold increase in the number of monocytes and 2-fold increase in lymphocytes. No severe side effects or antibody production was observed in cats after administration of G-CSF.