Optionen zur Therapie der felinen infektiösen Peritonitis – früher und heute

Zusammenfassung Die feline infektiöse Peritonitis (FIP) ist eine der häufigsten Infektionskrankheiten bei Katzen und verläuft unbehandelt tödlich. Bisher gibt es in Deutschland keine legal verfügbare wirksame Therapie. Therapieoptionen reichen von der symptomatischen Therapie (z. B. Glukokortikoide, Propentofyllin) über immunmodulatorische Ansätze (z. B. Interferone, Polyprenyl-Immunstimulanz) bis hin zur antiviralen Therapie mit einem Protease-Inhibitor (z. B. GC376) oder Nukleosid-Analoga (z. B. GS-441524, Remdesivir). Die symptomatische Therapie führt nicht zur Heilung der FIP, sondern nur zu einer kurzzeitigen Verbesserung der klinischen Symptome bei wenigen Katzen. Auch eine immunmodulatorische Therapie stellte sich als wenig erfolgversprechend heraus. Die antiviralen Medikamente GS-441524 und GC376 waren in mehreren Studien hochwirksam und konnten das Leben vieler an FIP erkrankten Katzen retten. Beide Wirkstoffe sind aktuell in Deutschland nicht zugelassen und können von Tierärzten nicht legal angewendet werden. Katzen dürfen aktuell nur in wenigen Ländern (z. B. Großbritannien und Australien) legal mit GS-441524 therapiert werden. GS-441524 wird daher von Katzenbesitzern in vielen anderen Ländern über den Schwarzmarkt bestellt und in Eigenregie angewendet. Dieser Artikel gibt eine Übersicht über verfügbare Therapieoptionen und einen Ausblick zur legalen Anwendung wirksamer antiviraler Medikamente.

[1]  E. Thiry,et al.  Feline Infectious Peritonitis: European Advisory Board on Cat Diseases Guidelines , 2023, Viruses.

[2]  R. Hofmann-Lehmann,et al.  Long-term follow-up of cats in complete remission after treatment of feline infectious peritonitis with oral GS-441524 , 2023, Journal of feline medicine and surgery.

[3]  F. Muller,et al.  An Optimized Bioassay for Screening Combined Anticoronaviral Compounds for Efficacy against Feline Infectious Peritonitis Virus with Pharmacokinetic Analyses of GS-441524, Remdesivir, and Molnupiravir in Cats , 2022, Viruses.

[4]  Liu Yang,et al.  Effect of GS-441524 in combination with the 3C-like protease inhibitor GC376 on the treatment of naturally transmitted feline infectious peritonitis , 2022, Frontiers in Veterinary Science.

[5]  W. Novicoff,et al.  Unlicensed Molnupiravir is an Effective Rescue Treatment Following Failure of Unlicensed GS-441524-like Therapy for Cats with Suspected Feline Infectious Peritonitis , 2022, Pathogens.

[6]  R. Hofmann-Lehmann,et al.  Clinical Follow-Up and Postmortem Findings in a Cat That Was Cured of Feline Infectious Peritonitis with an Oral Antiviral Drug Containing GS-441524 , 2022, Viruses.

[7]  Yuejun Shi,et al.  Adaptive Mutation in the Main Protease Cleavage Site of Feline Coronavirus Renders the Virus More Resistant to Main Protease Inhibitors , 2022, Journal of virology.

[8]  K. Hartmann,et al.  2022 AAFP/EveryCat Feline Infectious Peritonitis Diagnosis Guidelines , 2022, Journal of feline medicine and surgery.

[9]  M. Bohm Successful treatment of a South African cat with effusive feline infectious peritonitis with remdesivir. , 2022, Journal of the South African Veterinary Association.

[10]  R. Hofmann-Lehmann,et al.  Fecal Feline Coronavirus RNA Shedding and Spike Gene Mutations in Cats with Feline Infectious Peritonitis Treated with GS-441524 , 2022, Viruses.

[11]  D. Addie,et al.  Alpha-1 Acid Glycoprotein Reduction Differentiated Recovery from Remission in a Small Cohort of Cats Treated for Feline Infectious Peritonitis , 2022, Viruses.

[12]  Cat treated with remdesivir for feline infectious peritonitis. , 2022, The Veterinary record.

[13]  Jakob J. Malin,et al.  [Antiviral drugs : Potent agents, promising therapies for COVID‑19 and therapeutic limitations]. , 2022, Der Internist.

[14]  T. Takano,et al.  In vitro antiviral effects of GS-441524 and itraconazole combination against feline infectious peritonitis virus , 2022, Research in Veterinary Science.

[15]  Yukina Uemura,et al.  Therapeutic Effects of Mutian® Xraphconn on 141 Client-Owned Cats with Feline Infectious Peritonitis Predicted by Total Bilirubin Levels , 2021, Veterinary Sciences.

[16]  B. Koletzko,et al.  Curing Cats with Feline Infectious Peritonitis with an Oral Multi-Component Drug Containing GS-441524 , 2021, Viruses.

[17]  N. Pedersen,et al.  Investigation of monotherapy and combined anticoronaviral therapies against feline coronavirus serotype II in vitro , 2021, Journal of feline medicine and surgery.

[18]  M. Metzendorf,et al.  Remdesivir for the treatment of COVID-19. , 2021, The Cochrane database of systematic reviews.

[19]  W. Novicoff,et al.  Unlicensed GS-441524-Like Antiviral Therapy Can Be Effective for at-Home Treatment of Feline Infectious Peritonitis , 2021, Animals : an open access journal from MDPI.

[20]  R. Schinazi,et al.  Molnupiravir promotes SARS-CoV-2 mutagenesis via the RNA template , 2021, Journal of Biological Chemistry.

[21]  Jiashu Xie,et al.  Can remdesivir and its parent nucleoside GS-441524 be potential oral drugs? An in vitro and in vivo DMPK assessment , 2021, Acta Pharmaceutica Sinica B.

[22]  H. Ouyang,et al.  A retrospective study of clinical and laboratory features and treatment on cats highly suspected of feline infectious peritonitis in Wuhan, China , 2021, Scientific Reports.

[23]  O. Jarrett,et al.  Rapid Resolution of Non-Effusive Feline Infectious Peritonitis Uveitis with an Oral Adenosine Nucleoside Analogue and Feline Interferon Omega , 2020, Viruses.

[24]  R. Hofmann-Lehmann,et al.  Prevalence of Feline Coronavirus Shedding in German Catteries and Associated Risk Factors , 2020, Viruses.

[25]  T. Takano,et al.  Clinical efficacy of combination therapy of itraconazole and prednisolone for treating effusive feline infectious peritonitis , 2020, The Journal of veterinary medical science.

[26]  M. Méndez Bailón,et al.  The Prognostic Value of Eosinophil Recovery in COVID-19: A Multicentre, Retrospective Cohort Study on Patients Hospitalised in Spanish Hospitals , 2020, medRxiv.

[27]  M. Govendir,et al.  Pharmacokinetic Profile of Oral Administration of Mefloquine to Clinically Normal Cats: A Preliminary In-Vivo Study of a Potential Treatment for Feline Infectious Peritonitis (FIP) , 2020, Animals : an open access journal from MDPI.

[28]  N. Pedersen,et al.  Antiviral treatment using the adenosine nucleoside analogue GS‐441524 in cats with clinically diagnosed neurological feline infectious peritonitis , 2020, Journal of veterinary internal medicine.

[29]  M. Toda,et al.  Therapeutic effect of an anti-human-TNF-alpha antibody and itraconazole on feline infectious peritonitis , 2020, Archives of Virology.

[30]  J. Levy,et al.  Current knowledge about the antivirals remdesivir (GS-5734) and GS-441524 as therapeutic options for coronaviruses , 2020, One Health.

[31]  D. Addie,et al.  Oral Mutian®X stopped faecal feline coronavirus shedding by naturally infected cats , 2020, Research in Veterinary Science.

[32]  T. Takano,et al.  Endocytic Pathway of Feline Coronavirus for Cell Entry: Differences in Serotype-Dependent Viral Entry Pathway , 2019, Pathogens.

[33]  K. Hartmann,et al.  Diagnosis of Feline Infectious Peritonitis: A Review of the Current Literature , 2019, Viruses.

[34]  N. Pedersen,et al.  Characterization of amino acid substitutions in feline coronavirus 3C-like protease from a cat with feline infectious peritonitis treated with a protease inhibitor , 2019, Veterinary Microbiology.

[35]  N. Pedersen,et al.  Efficacy and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis , 2019, Journal of feline medicine and surgery.

[36]  T. Takano,et al.  Antiviral activity of itraconazole against type I feline coronavirus infection , 2019, Veterinary Research.

[37]  N. Pedersen,et al.  The nucleoside analog GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies , 2018, Veterinary Microbiology.

[38]  N. Pedersen,et al.  Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis , 2017, Journal of feline medicine and surgery.

[39]  T. Takano,et al.  The cholesterol transport inhibitor U18666A inhibits type I feline coronavirus infection , 2017, Antiviral Research.

[40]  V. M. Baylor,et al.  Polyprenyl Immunostimulant Treatment of Cats with Presumptive Non-Effusive Feline Infectious Peritonitis In a Field Study , 2017, Front. Vet. Sci..

[41]  K. Hartmann,et al.  Clinical and laboratory features of cats with feline infectious peritonitis – a retrospective study of 231 confirmed cases (2000–2010) , 2016, Journal of feline medicine and surgery.

[42]  N. Pedersen,et al.  Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor , 2016, PLoS pathogens.

[43]  J. Matthijnssens,et al.  Experimental feline enteric coronavirus infection reveals an aberrant infection pattern and shedding of mutants with impaired infectivity in enterocyte cultures , 2016, Scientific Reports.

[44]  P. Sheehy,et al.  Identification and characterisation of small molecule inhibitors of feline coronavirus replication , 2014, Veterinary Microbiology.

[45]  Niels C Pedersen,et al.  An update on feline infectious peritonitis: Diagnostics and therapeutics , 2014, The Veterinary Journal.

[46]  A. Kipar,et al.  Feline Infectious Peritonitis , 2014, Veterinary pathology.

[47]  K. Battaile,et al.  Broad-Spectrum Antivirals against 3C or 3C-Like Proteases of Picornaviruses, Noroviruses, and Coronaviruses , 2012, Journal of Virology.

[48]  A. Ray,et al.  Synthesis and antiviral activity of a series of 1′-substituted 4-aza-7,9-dideazaadenosine C-nucleosides , 2012, Bioorganic & Medicinal Chemistry Letters.

[49]  Kwok-Hung Chan,et al.  Discovery of Seven Novel Mammalian and Avian Coronaviruses in the Genus Deltacoronavirus Supports Bat Coronaviruses as the Gene Source of Alphacoronavirus and Betacoronavirus and Avian Coronaviruses as the Gene Source of Gammacoronavirus and Deltacoronavirus , 2012, Journal of Virology.

[50]  K. Hartmann,et al.  Randomized, Placebo Controlled Study of the Effect of Propentofylline on Survival Time and Quality of Life of Cats with Feline Infectious Peritonitis , 2011, Journal of veterinary internal medicine.

[51]  P. Sheehy,et al.  In vitro inhibition of feline coronavirus replication by small interfering RNAs , 2011, Veterinary Microbiology.

[52]  Chao-Nan Lin,et al.  Clinicopathological findings and disease staging of feline infectious peritonitis: 51 cases from 2003 to 2009 in Taiwan , 2011, Journal of Feline Medicine & Surgery.

[53]  Susanna K. P. Lau,et al.  Coronavirus Genomics and Bioinformatics Analysis , 2010, Viruses.

[54]  P. Woo,et al.  Coronavirus Diversity, Phylogeny and Interspecies Jumping , 2009, Experimental biology and medicine.

[55]  N. Pedersen,et al.  Significance of Coronavirus Mutants in Feces and Diseased Tissues of Cats Suffering from Feline Infectious Peritonitis , 2009, Viruses.

[56]  J. Bartges,et al.  Effect of Polyprenyl Immunostimulant on the survival times of three cats with the dry form of feline infectious peritonitis , 2009, Journal of Feline Medicine & Surgery.

[57]  M. Kent The cat with neurological manifestations of systemic disease. Key conditions impacting on the CNS , 2009, Journal of Feline Medicine & Surgery.

[58]  N. Pedersen A review of feline infectious peritonitis virus infection: 1963–2008 , 2009, Journal of Feline Medicine & Surgery.

[59]  H. Egberink,et al.  Effect of Feline Interferon‐Omega on the Survival Time and Quality of Life of Cats with Feline Infectious Peritonitis , 2007, Journal of veterinary internal medicine.

[60]  P. Masters,et al.  The Molecular Biology of Coronaviruses , 2006, Advances in Virus Research.

[61]  P. Lambert,et al.  Propionibacterium acnes , 2006, Letters in applied microbiology.

[62]  K. Uchida,et al.  Use of recombinant feline interferon and glucocorticoid in the treatment of feline infectious peritonitis , 2004, Journal of Feline Medicine & Surgery.

[63]  D. Hodgson,et al.  Kitten mortality in the United Kingdom: a retrospective analysis of 274 histopathological examinations (1986 to 2000) , 2002, Veterinary Record.

[64]  S. E. Andrew Feline Infectious Peritonitis , 2000, Veterinary Clinics of North America: Small Animal Practice.

[65]  J. Ziebuhr,et al.  Virus-encoded proteinases and proteolytic processing in the Nidovirales. , 2000, The Journal of general virology.

[66]  A. Hasegawa,et al.  Effect of thromboxane synthetase inhibitor on feline infectious peritonitis in cats. , 1998, The Journal of veterinary medical science.

[67]  Harry Vennema,et al.  Feline Infectious Peritonitis Viruses Arise by Mutation from Endemic Feline Enteric Coronaviruses , 1998, Virology.

[68]  M. Lai,et al.  The Molecular Biology of Coronaviruses , 1997, Advances in Virus Research.

[69]  N. Pedersen,et al.  Two related strains of feline infectious peritonitis virus isolated from immunocompromised cats infected with a feline enteric coronavirus , 1996, Journal of clinical microbiology.

[70]  O. Jarrett,et al.  Risk of feline infectious peritonitis in cats naturally infected with feline coronavirus. , 1995, American journal of veterinary research.

[71]  R. Weiss,et al.  Evaluation of free or liposome-encapsulated ribavirin for antiviral therapy of experimentally induced feline infectious peritonitis , 1993, Research in Veterinary Science.

[72]  O. Jarrett,et al.  A study of naturally occurring feline coronavirus infections in kittens , 1992, Veterinary Record.

[73]  T. Gruffydd-Jones,et al.  Feline infectious peritonitis: a review of clinicopathological changes in 65 cases, and a critical assessment of their diagnostic value , 1991, Veterinary Record.

[74]  J. Mullins,et al.  Alpha interferon (2b) in combination with zidovudine for the treatment of presymptomatic feline leukemia virus-induced immunodeficiency syndrome , 1990, Antimicrobial Agents and Chemotherapy.

[75]  R. Weiss,et al.  Effect of interferon or Propionibacterium acnes on the course of experimentally induced feline infectious peritonitis in specific-pathogen-free and random-source cats. , 1990, American journal of veterinary research.

[76]  R. Weiss,et al.  Inhibitory effects of ribavirin alone or combined with human alpha interferon on feline infectious peritonitis virus replication in vitro☆ , 1989, Veterinary Microbiology.

[77]  R. Strieter,et al.  Cellular and molecular regulation of tumor necrosis factor-alpha production by pentoxofylline , 1988 .

[78]  P. Gross,et al.  Antiviral Agents , 1988, Medical Clinics of North America.

[79]  K. Nicholson PROPERTIES OF ANTIVIRAL AGENTS Second of Two Parts , 1984, The Lancet.

[80]  N. Pedersen,et al.  Infection studies in kittens, using feline infectious peritonitis virus propagated in cell culture. , 1981, American journal of veterinary research.

[81]  N. Pedersen,et al.  An enteric coronavirus infection of cats and its relationship to feline infectious peritonitis. , 1981, American journal of veterinary research.

[82]  J. Timoney,et al.  Feline infectious peritonitis. , 1976, The Veterinary clinics of North America.

[83]  K. Heading,et al.  Prolonged survival of a cat diagnosed with feline infectious peritonitis by immunohistochemistry. , 2015, The Canadian veterinary journal = La revue veterinaire canadienne.

[84]  C. Schiffer,et al.  Viral Protease Inhibitors , 2009, Handbook of experimental pharmacology.

[85]  D. Watts Antiviral agents. , 1992, Obstetrics and gynecology clinics of North America.

[86]  R. Strieter,et al.  Cellular and molecular regulation of tumor necrosis factor-alpha production by pentoxifylline. , 1988, Biochemical and biophysical research communications.

[87]  N. Omawari,et al.  Pharmacological studies on the TXA2 synthetase inhibitor (E)-3-[p-(1H-imidazol-1-ylmethyl)phenyl]-2-propenoic acid (OKY-046). , 1986, Japanese journal of pharmacology.

[88]  N. Pedersen,et al.  Pathogenic differences between various feline coronavirus isolates. , 1984, Advances in experimental medicine and biology.

[89]  K. Nicholson Properties of antiviral agents. 2. , 1984, Lancet.