scholarly journals Diagnostic Value of Detecting Feline Coronavirus RNA and Spike Gene Mutations in Cerebrospinal Fluid to Confirm Feline Infectious Peritonitis

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 186
Author(s):  
Sandra Felten ◽  
Kaspar Matiasek ◽  
Christian M. Leutenegger ◽  
Laura Sangl ◽  
Stephanie Herre ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Confidence Interval ◽  
Clinical Signs ◽  
Gene Mutations ◽  
Diagnostic Value ◽  
Feline Infectious Peritonitis ◽  
Future Studies ◽  
Spike Gene ◽  
Neurological Signs ◽  
Feline Coronavirus

Background: Cats with neurologic feline infectious peritonitis (FIP) are difficult to diagnose. Aim of this study was to evaluate the diagnostic value of detecting feline coronavirus (FCoV) RNA and spike (S) gene mutations in cerebrospinal fluid (CSF). Methods: The study included 30 cats with confirmed FIP (six with neurological signs) and 29 control cats (eleven with neurological signs) with other diseases resulting in similar clinical signs. CSF was tested for FCoV RNA by 7b-RT-qPCR in all cats. In RT-qPCR-positive cases, S-RT-qPCR was additionally performed to identify spike gene mutations. Results: Nine cats with FIP (9/30, 30%), but none of the control cats were positive for FCoV RNA in CSF. Sensitivity of 7b-RT-qPCR in CSF was higher for cats with neurological FIP (83.3%; 95% confidence interval (95% CI) 41.8–98.9) than for cats with non-neurological FIP (16.7%; 95% CI 6.1–36.5). Spike gene mutations were rarely detected. Conclusions: FCoV RNA was frequently present in CSF of cats with neurological FIP, but only rarely in cats with non-neurological FIP. Screening for spike gene mutations did not enhance specificity in this patient group. Larger populations of cats with neurological FIP should be explored in future studies.

scholarly journals Detection of feline coronavirus spike gene mutations as a tool to diagnose feline infectious peritonitis

2016 ◽  
Vol 19 (4) ◽  
pp. 321-335 ◽  
Author(s):  
Sandra Felten ◽  
Karola Weider ◽  
Stephanie Doenges ◽  
Stefanie Gruendl ◽  
Kaspar Matiasek ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Control Group ◽  
Nested Polymerase Chain Reaction ◽  
Feline Infectious Peritonitis ◽  
Spike Gene ◽  
S Gene ◽  
Pcr Products ◽  
Study Population ◽  
Polymerase Chain ◽  
Feline Coronavirus

Objectives Feline infectious peritonitis (FIP) is an important cause of death in the cat population worldwide. The ante-mortem diagnosis of FIP in clinical cases is still challenging. In cats without effusion, a definitive diagnosis can only be achieved post mortem or with invasive methods. The aim of this study was to evaluate the use of a combined reverse transcriptase nested polymerase chain reaction (RT-nPCR) and sequencing approach in the diagnosis of FIP, detecting mutations at two different nucleotide positions within the spike (S) gene. Methods The study population consisted of 64 cats with confirmed FIP and 63 cats in which FIP was initially suspected due to similar clinical or laboratory signs, but that were definitively diagnosed with another disease. Serum/plasma and/or effusion samples of these cats were examined for feline coronavirus (FCoV) RNA by RT-nPCR and, if positive, PCR products were sequenced for nucleotide transitions within the S gene. Results Specificity of RT-nPCR was 100% in all materials (95% confidence interval [CI] in serum/plasma 83.9–100.0; 95% CI in effusion 93.0–100.0). The specificity of the sequencing step could not be determined as none of the cats of the control group tested positive for FCoV RNA. Sensitivity of the ‘combined RT-nPCR and sequencing approach’ was 6.5% (95% CI 0.8–21.4) in serum/plasma and 65.3% (95% CI 50.4–78.3) in effusion. Conclusions and relevance A positive result is highly indicative of the presence of FIP, but as none of the control cats tested positive by RT-nPCR, it was not possible to confirm that the FCoV mutant described can only be found in cats with FIP. Further studies are necessary to evaluate the usefulness of the sequencing step including FCoV-RNA-positive cats with and without FIP. A negative result cannot be used to exclude the disease, especially when only serum/plasma samples are available.

scholarly journals Detection of feline coronavirus RNA, spike gene mutations, and feline coronavirus antigen in macrophages in aqueous humor of cats in the diagnosis of feline infectious peritonitis

2020 ◽  
Vol 32 (4) ◽  
pp. 527-534
Author(s):  
Laura Sangl ◽  
Sandra Felten ◽  
Kaspar Matiasek ◽  
Stefanie Dörfelt ◽  
Michele Bergmann ◽  
...  
Keyword(s):  
Aqueous Humor ◽  
Point Mutations ◽  
Gene Mutations ◽  
Control Group ◽  
Complex Method ◽  
Predictive Values ◽  
Feline Infectious Peritonitis ◽  
Spike Gene ◽  
Sensitivity Specificity ◽  
Feline Coronavirus

Uveitis is common in cats, and is often a feature of feline infectious peritonitis (FIP). We evaluated 3 tools for detection of feline coronavirus (FCoV) in aqueous humor: 1) a 7b gene reverse-transcription real-time PCR ( 7b-RT-rtPCR) assay to detect FCoV RNA, 2) a spike gene mutation RT-rtPCR ( S-RT-rtPCR) assay to detect 2 point mutations in the spike gene of FCoV in cats positive by 7b-RT-rtPCR, and 3) immunocytochemistry (ICC) for detection of FCoV antigen in aqueous humor macrophages. We studied 58 cats, including 31 cats with FIP and 27 control cats. FIP was excluded by postmortem examination and negative immunohistochemistry (IHC). Aqueous humor samples obtained postmortem were assessed using 7b-RT-rtPCR in all cats, and positive samples were evaluated with S-RT-rtPCR. ICC evaluation of aqueous humor samples from 36 of the 58 cats was done using an avidin–biotin complex method and monoclonal anti-FCoV IgG 2A. Sensitivity, specificity, and negative and positive predictive values were calculated including 95% CIs. 7b-RT-rtPCR had a specificity of 100.0% (95% CI: 87.2–100.0) and sensitivity of 35.5% (95% CI: 19.2–54.6). Specificity of S-RT-rtPCR could not be determined because there were no FCoV 7b-RT-rtPCR–positive samples in the control group. Sensitivity of S-RT-rtPCR was 12.9% (95% CI 3.6–29.8). Sensitivity and specificity of ICC were 62.5% (95% CI: 40.6–81.2) and 80.0% (95% CI: 44.4–97.5), respectively. The combination of 7b-RT-rtPCR and IHC could be useful in diagnosing FIP; S-RT-rtPCR did not add value; and ICC of aqueous humor samples cannot be recommended for the diagnosis of FIP.

scholarly journals Detection of feline coronavirus in cerebrospinal fluid for diagnosis of feline infectious peritonitis in cats with and without neurological signs

2015 ◽  
Vol 18 (2) ◽  
pp. 104-109 ◽  
Author(s):  
Stephanie J Doenges ◽  
Karin Weber ◽  
Roswitha Dorsch ◽  
Robert Fux ◽  
Andrea Fischer ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Feline Infectious Peritonitis ◽  
Neurological Signs ◽  
Feline Coronavirus

scholarly journals Feline Coronavirus infections and feline infectious peritonitis

2018 ◽  
Vol 50 (3) ◽  
pp. 199
Author(s):  
A. TZIVARA (Α. ΤΖΙΒΑΡΑ) ◽  
S. K. KRITAS (Σ.Κ. ΚΡΗΤΑΣ)
Keyword(s):  
Gastrointestinal Disease ◽  
Clinical Signs ◽  
Asymptomatic Infection ◽  
Temperature Sensitive ◽  
Feline Infectious Peritonitis ◽  
Antibody Titers ◽  
Coronavirus Infection ◽  
Different Strains ◽  
Physical Findings ◽  
Feline Coronavirus

Cats are susceptible to infection with several different strains of feline Coronavirus. Depending on the involved strain, clinical signs may range from asymptomatic infection to gastrointestinal disease or fibrinous serositis and disseminated vasculitis, commonly known as feline infectious peritonitis (FIP). Excretion of virus by infected cats into the environment occurs by faeces, oronasal secretions and urine. The feline coronaviruses are rapidly inactivated by most disinfectants. Clinical diagnosis of Coronavirus infection is made by evaluating the case history, physical findings, laboratory results, Coronavirus antibody titers and tissue biopsy. A temperature-sensitive feline infectious peritonitis virus vaccine has become available for healthy 16 week of age or older cats.

scholarly journals Diagnosis of Feline Infectious Peritonitis: A Review of the Current Literature

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1068 ◽  
Author(s):  
Sandra Felten ◽  
Katrin Hartmann
Keyword(s):  
Sensitivity And Specificity ◽  
Diagnostic Tests ◽  
Clinical Signs ◽  
Etiologic Agent ◽  
Diagnostic Methods ◽  
Sample Material ◽  
Feline Infectious Peritonitis ◽  
Veterinary Practitioner ◽  
Laboratory Changes ◽  
Feline Coronavirus

Feline infectious peritonitis (FIP) is a fatal disease that poses several challenges for veterinarians: clinical signs and laboratory changes are non-specific, and there are two pathotypes of the etiologic agent feline coronavirus (FCoV), sometimes referred to as feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV) that vary fundamentally in their virulence, but are indistinguishable by a number of diagnostic methods. This review focuses on all important steps every veterinary practitioner has to deal with and new diagnostic tests that can be considered when encountering a cat with suspected FIP with the aim to establish a definitive diagnosis. It gives an overview on all available direct and indirect diagnostic tests and their sensitivity and specificity reported in the literature in different sample material. By providing summarized data for sensitivity and specificity of each diagnostic test and each sample material, which can easily be accessed in tables, this review can help to facilitate the interpretation of different diagnostic tests and raise awareness of their advantages and limitations. Additionally, diagnostic trees depict recommended diagnostic steps that should be performed in cats suspected of having FIP based on their clinical signs or clinicopathologic abnormalities. These steps can easily be followed in clinical practice.

scholarly journals A retrospective study of clinical and laboratory features and treatment on cats highly suspected of feline infectious peritonitis in Wuhan, China

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yiya Yin ◽  
Ting Li ◽  
Chaohao Wang ◽  
Xiaoya Liu ◽  
Hehao Ouyang ◽  
...  
Keyword(s):  
Clinical Signs ◽  
Clinical Manifestations ◽  
Viral Disease ◽  
Diagnostic Value ◽  
Diverse Range ◽  
Feline Infectious Peritonitis ◽  
Amyloid A ◽  
Laboratory Features ◽  
Clinical Records ◽  
G Ratio

AbstractFeline infectious peritonitis (FIP) is a systemic, potentially fatal viral disease. The objectives of this study were to review clinical and laboratory features and treatment of cats highly suspected of FIP in Wuhan, China. The clinical records of 127 cats highly suspected of FIP were reviewed for history, clinical signs, physical findings, and diagnostic test results. Sex, neutering status, breed, age, and month of onset of disease were compared with the characteristics of the clinic population. Age and neutering status were significantly correlated with FIP-suspicion. Sex, breed and onset month were not associated with FIP. There were many more FIP-suspected cases in cats in young cats or male intact cats. Effusion was observed in 85.8% of the FIP-suspected cats. Increased serum amyloid A (SAA) and lymphopenia were common laboratory abnormalities in the FIP cases. Furthermore, 91.7% of the cats highly suspected of FIP had an albumin/globulin (A/G) ratio < 0.6, while 85.3% had an A/G ratio < 0.5. The mortality rate for FIP-suspected cats was 67%, and six submitted cases were confirmed by FIP-specific immunohistochemistry. Of the 30 cats treated with GS-441524 and/or GC376, 29 were clinically cured. The study highlights the diverse range of clinical manifestations by clinicians in diagnosing this potentially fatal disease. A/G ratio and SAA were of higher diagnostic value. GS-441524 and GC376 were efficient for the treatment of FIP-suspected cats.

scholarly journals Distinct mutation in the feline coronavirus spike protein cleavage activation site in a cat with feline infectious peritonitis-associated meningoencephalomyelitis

2019 ◽  
Vol 5 (1) ◽  
pp. 205511691985610 ◽  
Author(s):  
Nicole M André ◽  
Brieuc Cossic ◽  
Emma Davies ◽  
Andrew D Miller ◽  
Gary R Whittaker
Keyword(s):  
Complete Blood Count ◽  
Clinical Signs ◽  
Spike Protein ◽  
Protein Cleavage ◽  
Early Presentation ◽  
Feline Infectious Peritonitis ◽  
The Central Nervous System ◽  
Brain And Spinal Cord ◽  
Feline Coronavirus

Case summary This report describes a cat with chronic, progressive, non-painful, non-lateralizing multifocal neurologic clinical signs associated with feline infectious peritonitis (FIP). The cat initially presented as underweight, despite a good appetite, and a complete blood count showed non-regenerative anemia. Three months later the cat was returned having developed ataxia and paraparesis, which then progressed over 2 months to tetraparesis, tail plegia, urinary and fecal incontinence, and titubation. Histologic examination of the tissues with subsequent immunohistochemistry confirmed FIP-associated meningoencephalomyelitis following necropsy. Molecular analysis of the coronavirus spike protein within the tissues identified a specific, functionally relevant amino acid change (R793M), which was only identified in tissues associated with the central nervous system (ie, brain and spinal cord). Relevance and novel information This case report describes an early presentation of a cat with primarily neurologic FIP, with molecular characterization of the virus within various tissues.

scholarly journals Diagnostic utility of cerebrospinal fluid immunocytochemistry for diagnosis of feline infectious peritonitis manifesting in the central nervous system

2016 ◽  
Vol 19 (6) ◽  
pp. 576-585 ◽  
Author(s):  
Stefanie Gruendl ◽  
Kaspar Matiasek ◽  
Lara Matiasek ◽  
Andrea Fischer ◽  
Sandra Felten ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Immunocytochemical Staining ◽  
Predictive Values ◽  
Feline Infectious Peritonitis ◽  
Neurological Signs ◽  
Highly Sensitive ◽  
The Central Nervous System ◽  
Sensitivity Specificity

Objectives The aim of the study was to evaluate whether an ante-mortem diagnosis of central nervous system (CNS) feline infectious peritonitis (FIP) is possible via immunocytochemical staining (ICC) of feline coronavirus antigen (FCoV) within macrophages of cerebrospinal fluid (CSF). Methods Prospectively, CSF samples of 41 cats were investigated, including cats with histopathologically confirmed FIP and neurological signs (n = 10), cats with confirmed FIP without CNS involvement (n = 11), cats with neurological signs but another confirmed CNS disease (n = 17), and cats without neurological signs and a disease other than FIP (n = 3). ICC staining of CSF macrophages was performed in all cats. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of CSF ICC were calculated. Results Of 10 samples from cats with CNS FIP, eight had detectable CSF macrophages, seven of which were positive for FCoV. Ten of 11 samples from cats with confirmed FIP without neurological signs had macrophages in the CSF, with all 10 being ICC-positive. In cats with other CNS disorders, 11/17 had macrophages, two of which stained positively. In cats with diseases other than FIP and without neurological disorders, 2/3 revealed macrophages, with one cat showing positive ICC staining. Diagnosis of FIP via CSF ICC had a sensitivity of 85.0% and a specificity of 83.3%. PPV and NPV were 85.0% and 83.3%. Conclusions and relevance CSF ICC is a highly sensitive test for ante-mortem diagnosis of FIP manifesting in the CNS. However, CNS ICC specificity is too low to confirm FIP and the method should only be applied in conjunction with other features such as CSF cytology. CNS ICC could be helpful to discover pre-neurological stages of CNS FIP.

scholarly journals The diagnostic value of IgG index versus oligoclonal bands in cerebrospinal fluid of patients with multiple sclerosis

2020 ◽  
Vol 6 (1) ◽  
pp. 205521731990129 ◽  
Author(s):  
Cecilia Smith Simonsen ◽  
Heidi Øyen Flemmen ◽  
Trine Lauritzen ◽  
Pål Berg-Hansen ◽  
Stine Marit Moen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Confidence Interval ◽  
Positive Predictive Value ◽  
Immunoglobulin G ◽  
Predictive Value ◽  
Diagnostic Value ◽  
Oligoclonal Bands ◽  
Diagnostic Process ◽  
Oligoclonal Band

Background Diagnostic criteria for multiple sclerosis have been developed to guide the diagnostic process. In the latest revision of the McDonald criteria, the presence of oligoclonal bands may replace the need for dissemination in time. The aim of this study is to investigate if the less time-consuming analysis of immunoglobulin G index in cerebrospinal fluid can safely predict the findings of oligoclonal bands. Methods This is a retrospective study of patients with multiple sclerosis at three hospitals in South-East Norway where lumbar puncture is performed routinely. We included patients diagnosed with multiple sclerosis after 2005 with known oligoclonal band status and an immunoglobulin G index score. Results Of 1295 patients diagnosed during or after 2005, 93.8% were oligoclonal band positive at diagnosis. Of 842 multiple sclerosis patients with known immunoglobulin G index and oligoclonal band status, 93.3% were oligoclonal band positive and 76.7% had an elevated immunoglobulin G index. The positive predictive value of a high immunoglobulin G index when oligoclonal bands are positive was 99.4% (95% confidence interval 98.4–99.8%). The negative predictive value of a normal immunoglobulin G index when oligoclonal bands are negative was 26.5% (95% confidence interval 23.5–29.9%). Conclusion An immunoglobulin G index >0.7 has a positive predictive value >99% for oligoclonal bands. An elevated immunoglobulin G index adds diagnostic value versus oligoclonal bands and saves time in the diagnostic process.

scholarly journals Intrahost Diversity of Feline Coronavirus: A Consensus between the Circulating Virulent/Avirulent Strains and the Internal Mutation Hypotheses?

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Aline S. Hora ◽  
Karen M. Asano ◽  
Juliana M. Guerra ◽  
Ramon G. Mesquita ◽  
Paulo Maiorka ◽  
...  
Keyword(s):  
Amino Acid ◽  
Molecular Diversity ◽  
Gene Tree ◽  
Gene Mutations ◽  
Geographic Pattern ◽  
M Gene ◽  
Feline Infectious Peritonitis ◽  
Faecal Samples ◽  
Feline Coronavirus

To evaluate the most controversial issue concerning current feline coronavirus (FCoV) virology, the coexisting hypotheses of the intrahost and interhost origins of feline infectious peritonitis virus (FIPV) in regard to the pathogenesis of feline infectious peritonitis (FIP), this study aimed to assess the molecular diversity of the membrane gene FCoVs in 190 samples from 10 cats with signs of FIP and in 5 faecal samples from cats without signs of FIP. All samples from the non-FIP cats and 25.26% of the samples from the FIP cats were positive for the FCoV membrane (M) gene. Mutations in this gene consisted of SNP changes randomly scattered among the sequences; few mutations resulted in amino acid changes. No geographic pattern was observed. Of the cats without FIP that harboured FECoV, the amino acid sequence identities for the M gene were 100% among cats (Cats 1–3) from the same cattery, and the overall sequence identity for the M gene was ≥91%. In one cat, two different lineages of FCoV, one enteric and one systemic, were found that segregated apart in the M gene tree. In conclusion, the in vivo mutation transition hypothesis and the circulating high virulent-low virulent FCoV hypothesis have been found to be plausible according to the results obtained from sequencing the M gene.

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