A retrospective study of clinical and laboratory features and treatment on cats highly suspected of feline infectious peritonitis in Wuhan, China.
04 Mar 2021-Scientific Reports (Springer Science and Business Media LLC)-Vol. 11, Iss: 1, pp 5208-5208
TL;DR: Wu et al. as mentioned in this paper reviewed clinical and laboratory features and treatment of cats highly suspected of FIP in Wuhan, China, for history, clinical signs, physical findings, and diagnostic test results.
Abstract: Feline 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.
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TL;DR: In this paper, the authors evaluated efficacy and toxicity of the multi-component drug Xraphconn® in vitro and as oral treatment in cats with spontaneous FIP by examining survival rate, development of clinical and laboratory parameters, viral loads, anti-FCoV antibodies, and adverse effects.
Abstract: Feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) is a common dis-ease in cats, fatal if untreated, and no effective treatment is currently legally available. The aim of this study was to evaluate efficacy and toxicity of the multi-component drug Xraphconn® in vitro and as oral treatment in cats with spontaneous FIP by examining survival rate, development of clinical and laboratory parameters, viral loads, anti-FCoV antibodies, and adverse effects. Mass spectrometry and nuclear magnetic resonance identified GS-441524 as an active component of Xraphconn®. Eighteen cats with FIP were prospectively followed up while being treated orally for 84 days. Values of key parameters on each examination day were compared to values before treatment initiation using linear mixed-effect models. Xraphconn® displayed high virucidal activity in cell culture. All cats recovered with dramatic improvement of clinical and laboratory parameters and massive reduction in viral loads within the first few days of treatment without serious adverse effects. Oral treatment with Xraphconn® containing GS-441524 was highly effective for FIP without causing serious adverse effects. This drug is an excellent option for the oral treatment of FIP and should be trialed as potential effective treatment option for other severe coronavirus-associated diseases across species.
13 citations
TL;DR: This case series provides interesting data on point mutations associated with the development of FIP and provides support for a ‘circulating virulent–avirulent theory’ of Fip pathogenesis in a small shelter outbreak.
Abstract: Case series summary This case series describes three shelter-housed cats concurrently diagnosed with feline infectious peritonitis (FIP). The cats were from a cohort of seven surrendered from the site of a house fire. The three cats presented with mild upper respiratory signs. Within 10 days they clinically declined: progressive signs included pyrexia, icterus, lethargy, anorexia and cavitary effusions. Necropsy followed by histopathology and immunohistochemistry confirmed a diagnosis of FIP in all three. Molecular analysis of the causative feline coronavirus (FCoV) revealed varied amino acid alterations in the spike gene both between cats and between sample types in individual cats. A fourth cat from the cohort remained healthy in the shelter but succumbed to FIP 6 weeks post-adoption. Relevance and novel information This case series places FCoV genetic sequences in the context of clinical signs in a small shelter outbreak. Each of the three cats concurrently developed a slightly different clinical presentation. PCR amplification and genetic sequencing revealed that two cats shared an S1/S2 cleavage site mutation (R790S) previously described to be associated with the development of FIP; one of the cats had an additional S1/S2 cleavage site mutation (R793S). The third cat had a single, identical S1/S2 point mutation (R790G) unique from the other two cats; the R790G mutation has not been previously reported. This case series provides interesting data on point mutations associated with the development of FIP and provides support for a ‘circulating virulent–avirulent theory’ of FIP pathogenesis in a small shelter outbreak.
12 citations
TL;DR: The 2022 AAFP/EveryCat Feline Infectious Peritonitis Diagnosis Guidelines as discussed by the authors were developed to provide veterinarians with essential information to aid their ability to recognize cats presenting with FIP.
Abstract: Feline infectious peritonitis (FIP) is one of the most important infectious diseases and causes of death in cats; young cats less than 2 years of age are especially vulnerable. FIP is caused by a feline coronavirus (FCoV). It has been estimated that around 0.3% to 1.4% of feline deaths at veterinary institutions are caused by FIP.This document has been developed by a Task Force of experts in feline clinical medicine as the 2022 AAFP/EveryCat Feline Infectious Peritonitis Diagnosis Guidelines to provide veterinarians with essential information to aid their ability to recognize cats presenting with FIP.Nearly every small animal veterinary practitioner will see cases. FIP can be challenging to diagnose owing to the lack of pathognomonic clinical signs or laboratory changes, especially when no effusion is present. A good understanding of each diagnostic test's sensitivity, specificity, predictive value, likelihood ratio and diagnostic accuracy is important when building a case for FIP. Before proceeding with any diagnostic test or commercial laboratory profile, the clinician should be able to answer the questions of 'why this test?' and 'what do the results mean?' Ultimately, the approach to diagnosing FIP must be tailored to the specific presentation of the individual cat.Given that the disease is fatal when untreated, the ability to obtain a correct diagnosis is critical. The clinician must consider the individual patient's history, signalment and comprehensive physical examination findings when selecting diagnostic tests and sample types in order to build the index of suspicion 'brick by brick'. Research has demonstrated efficacy of new antivirals in FIP treatment, but these products are not legally available in many countries at this time. The Task Force encourages veterinarians to review the literature and stay informed on clinical trials and new drug approvals.
11 citations
TL;DR: In this article, a review of antiviral therapy against FCoV both in vitro and in vivo, with the description of their mechanisms of action when known, highlights the molecules which could have a broader effect on different coronaviruses.
Abstract: Feline coronaviruses (FCoV) are common viral pathogens of cats. They usually induce asymptomatic infections but some FCoV strains, named Feline Infectious Peritonitis Viruses (FIPV) lead to a systematic fatal disease, the feline infectious peritonitis (FIP). While no treatments are approved as of yet, numerous studies have been explored with the hope to develop therapeutic compounds. In recent years, two novel molecules (GS-441524 and GC376) have raised hopes given the encouraging results, but some concerns about the use of these molecules persist, such as the fear of the emergence of viral escape mutants or the difficult tissue distribution of these antivirals in certain affected organs. This review will summarize current findings and leads in the development of antiviral therapy against FCoV both in vitro and in vivo, with the description of their mechanisms of action when known. It highlights the molecules, which could have a broader effect on different coronaviruses. In the context of the SARS-CoV-2 pandemic, the development of antivirals is an urgent need and FIP could be a valuable model to help this research area.
11 citations
TL;DR: In this article, the authors investigated the clinical signs, duration, and amount of FCV shedding, RNAemia, haematological changes and acute phase protein reaction in SPF cats after subcutaneous modified-live single strain FCV vaccination or placebo injection and two subsequent oronasal heterologous FCV challenge infections with two different field strains.
Abstract: Feline calicivirus (FCV) is a common cat virus causing clinical signs such as oral ulcerations, fever, reduced general condition, pneumonia, limping and occasionally virulent-systemic disease. Efficacious FCV vaccines protect against severe disease but not against infection. FCV is a highly mutagenic RNA virus whose high genetic diversity poses a challenge in vaccine design. The use of only one modified-live FCV strain over several decades might have driven the viral evolution towards more vaccine-resistant variants. The present study investigated the clinical signs, duration, and amount of FCV shedding, RNAemia, haematological changes and acute phase protein reaction in SPF cats after subcutaneous modified-live single strain FCV vaccination or placebo injection and two subsequent oronasal heterologous FCV challenge infections with two different field strains. Neither clinical signs nor FCV shedding from the oropharynx and FCV RNAemia were detected after vaccination. After the first experimental infection, vaccinated cats had significantly lower clinical scores, less increased body temperature and lower acute phase protein levels than control cats. The viral RNA loads from the oropharynx and duration and amount of RNAemia were significantly lower in the vaccinated animals. No clinical signs were observed in any of the cats after the second experimental infection. In conclusion, FCV vaccination was beneficial for protecting cats from severe clinical signs, reducing viral loads and inflammation after FCV challenge.
5 citations
References
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12 Aug 2005
TL;DR: Part I: Viral, Rickettsial, And Mycoplasmal Diseases, and Part II: Clinical Problems.
Abstract: Section I: Viral, Rickettsial, And Mycoplasmal Diseases. Laboratory Diagnosis of Viral and Rickettsial Infections. Antiviral Drugs. Canine Distemper. Infectious Canine Hepatitis and Canine Acidophil Cell Hepatitis. Canine Herpesvirus Infection. Canine Infectious Tracheobronchitis. Nonrespiratory Parainfluenza Virus Infection of Dogs. Canine Viral Enteritis. Canine Viral Papillomatosis. Feline Panleukopenia. Feline Coronavirus Infection. Feline Enteric Viral Infections. Feline Viral Neoplasia. Feline Immunodeficiency Virus Infection. Feline Adenovirus Infection. Feline Respiratory Disease. Feline Syncytium-Forming Virus Infection. Feline Paramyxovirus Infections. Feline Poxvirus Infection. Hantavirus Infection. Feline Viral Papillomatosis. Rabies. Pseudorabies. Enterovirus Infections. Mumps and Influenza Virus Infections. Arboviral Infections. Salmon Poisoning Disease. Ehrlichiosis. Rocky Mountain Spotted Fever, Q Fever, And Typhus. Haemobartonellosis. Chlamydial Infections. Mycoplasmal, Ureaplasmal, And L-Form Infections. Section Ii: Bacterial Diseases. Laboratory Diagnosis of Bacterial Infections. Antibacterial Chemotherapy. Streptococal and Other Gram-Positive Bacterial Infections. Staphylococcal Infections. Gram-Negative Bacterial Infections. Endotoxemia. Enteric Bacterial Infections. Canine Brucellosis. Anaerobic Infections. Botulism. Tetanus. Leptospirosis. Lyme Borreliosis. Miscellaneous Bacterial Infections. Plague. Tularemia. Actinomycosis and Nocardiosis. Mycobacterial Infections. Dermatophilosis. Feline Abscesses. Bite Wound Infections. Bartonellosis. Surgical and Traumatic Infections. Section Iii: Fungal Diseases. Laboratory Diagnosis of Fungal and Algal Infections. Antifungal Chemotherapy. Dermatophytosis. Blastomycosis. Histoplasmosis. Cryptococcosis. Coccidioidomycosis. Sporotrichosis. Rhinosporidiosis. Aspergillosis and Penicilliosis. Candidiasis, Torulopsosis, And Rhodotorulosis. Trichospornosis. Miscellaneous Fungal Infections. Prothotecosis. Section Iv: Protozoal Diseases. Laboratory Diagnosis of Protozoal Infections. Antiprotozoal Chemotherapy. Trypanosomiasis. Leishmaniasis. Hepatozoonosis. Encephalitozoonosis. Cytauxzoonosis. Babesiosis. Enteric Protozoal Infections. Acanthamebiasis. Toxoplasmosis and Neosporosis. Enteric Coccidiosis. Cryptosporidiosis and Cyclosporiasis. Pneumocystosis. Neurologic Diseases of Suspected Infectious Origin. Section V: Clinical Problems. Integumentary Infections. Musculoskeletal Infections. Cardiovascular Infections. Respiratory Infections. Gastrointestinal and Intra-Abdominal Infections. Hepatobiliary Infections. Genitourinary Infections. Central Nervous System Infections. Ocular Infections. Environmental Factors in Infectious Diseases. Immunodeficiencies and Infectious Diseases. Fever. Prevention and Management of Infection in Catteries. Prevention and Management of Infections in Kennels. Immunocompromised People and Pets. Immunoprophylaxis and Immunotherapy. Appendices: Canine Immunization Recommendations. Feline Immunization Recommendations. Canineand Feline Biologics Manufacturers and Products Available Worldwide. Compendium of Animal Rabies Control, 1998 National Association of State Public Health Veterinarians, Inc. Laboratory Testing for Infectious Diseases of Dogs and Cats. Manufacturers of Diagnostic Test Kits and Their Products. Infectious Disease Rule-Outs for Medical Problems. Antimicrobial Drug Formulary.
1,367 citations
TL;DR: The immune system is regulated by the gonadal steroids estrogen, androgen, and progesterone, but the circulating levels of these steroids can also be affected by immune system function.
Abstract: The immune system is regulated by the gonadal steroids estrogen, androgen, and progesterone, but the circulating levels of these steroids can also be affected by immune system function. Such interactions appear to be mediated through the hypothalamic-pituitary-gonadal-thymic axis and depend on pituitary luteinizing hormone released by thymic factors under the control of the gonadal steroids.
1,044 citations
TL;DR: F eline infectious peritonitis (FIP) was first described as an ‘important disorder of cats’ by Holzworth in 1963 and a clinico-pathologic conference on this disorder was published in the following year.
Abstract: F eline infectious peritonitis (FIP) was first described as an ‘important disorder of cats’ by Holzworth in 1963 at the Angell Memorial Animal Hospital, Boston and a clinico-pathologic conference on this disorder was published in the following year. The disease was thought to be infectious but no specific etiologic agent was identified at the time. Wolfe and Griesemer were the first to propose that FIP was caused by a virus. Zook et al observed virus particles in the tissues of experimentally infected cats, but were unable to characterize the agent. Ward recognized the close similarities of FIP virus (FIPV) in tissues to members of the family Coronaviridae. In 1972 Montali and Strandberg were the first to report that FIPV infection could be either granulomatous (dry, parenchymatous) or effusive (wet, non-parenchymatous). The close genetic relationship of FIPV to coronaviruses of dogs and swine was first reported by Pedersen et al in 1978. Fully virulent FIPV was first propagated in vitro in autochthonous macrophage cultures from experimentally infected cats and later in tissue culture. It was also replicated in the epithelium of intestinal ring cultures. A strain of FIPV (FIPV-UCD1) was first propagated in continuously passsaged Felis catus, whole fetus-4 (Fcwf-4) cells and shown to be virulent when inoculated into cats. The Fcwf-4 cells were later found to be of
387 citations
Wesley C. Van Voorhis1, John H. Adams2, Roberto Adelfio3, Roberto Adelfio4 +197 more•Institutions (62)
TL;DR: The results reveal the immense potential for translating the dispersed expertise in biological assays involving human pathogens into drug discovery starting points, by providing open access to new families of molecules, and emphasize how a small additional investment made to help acquire and distribute compounds, and sharing the data, can catalyze drug discovery for dozens of different indications.
Abstract: A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34%) of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments and medicinal chemistry programs. The data for all of these assays are presented and analyzed to show how outstanding leads for many indications can be selected. These results reveal the immense potential for translating the dispersed expertise in biological assays involving human pathogens into drug discovery starting points, by providing open access to new families of molecules, and emphasize how a small additional investment made to help acquire and distribute compounds, and sharing the data, can catalyze drug discovery for dozens of different indications. Another lesson is that when multiple screens from different groups are run on the same library, results can be integrated quickly to select the most valuable starting points for subsequent medicinal chemistry efforts.
377 citations
TL;DR: It is found that antiviral treatment led to full recovery of cats when treatment was started at a stage of disease that would be otherwise fatal if left untreated, and results indicate that continuous virus replication is required for progression of immune-mediated inflammatory disease of FIP.
Abstract: Coronaviruses infect animals and humans causing a wide range of diseases. The diversity of coronaviruses in many mammalian species is contributed by relatively high mutation and recombination rates during replication. This dynamic nature of coronaviruses may facilitate cross-species transmission and shifts in tissue or cell tropism in a host, resulting in substantial change in virulence. Feline enteric coronavirus (FECV) causes inapparent or mild enteritis in cats, but a highly fatal disease, called feline infectious peritonitis (FIP), can arise through mutation of FECV to FIP virus (FIPV). The pathogenesis of FIP is intimately associated with immune responses and involves depletion of T cells, features shared by some other coronaviruses like Severe Acute Respiratory Syndrome Coronavirus. The increasing risks of highly virulent coronavirus infections in humans or animals call for effective antiviral drugs, but no such measures are yet available. Previously, we have reported the inhibitors that target 3C-like protease (3CLpro) with broad-spectrum activity against important human and animal coronaviruses. Here, we evaluated the therapeutic efficacy of our 3CLpro inhibitor in laboratory cats with FIP. Experimental FIP is 100% fatal once certain clinical and laboratory signs become apparent. We found that antiviral treatment led to full recovery of cats when treatment was started at a stage of disease that would be otherwise fatal if left untreated. Antiviral treatment was associated with a rapid improvement in fever, ascites, lymphopenia and gross signs of illness and cats returned to normal health within 20 days or less of treatment. Significant reduction in viral titers was also observed in cats. These results indicate that continuous virus replication is required for progression of immune-mediated inflammatory disease of FIP. These findings may provide important insights into devising therapeutic strategies and selection of antiviral compounds for further development for important coronaviruses in animals and humans.
198 citations