by Maria Lyraki, DVM MSc
Feline coronavirus (FCoV) is the causative agent of the serious disease of feline infectious peritonitis (FIP). FCoV has a cell tropism for the enterocytes and usually causes clinical signs of enteritis or no clinical signs at all.
Being an RNA virus though, FCoV has a high level of genetic variation due to frequent errors (mutations) during RNA replication. The hypothesis is that these mutations can occasionally facilitate the switching of cell tropism from a mostly mild enteric (less-virulent) FCoV pathotype to an FIP-associated FCoV pathotype.
When FIP develops, the replicating FCoV in monocytes causes damage to the blood vessel walls, allowing plasma to leak out of the vessels; this can appear clinically as an effusion in the abdominal, thoracic and/or pericardial cavities (wet FIP form). In more chronic forms of FIP, granulomas result on affected organs (dry FIP form). Dry FIP can involve any organ, including nervous system (neurological form) and eyes (ocular form).
Feline infectious peritonitis (FIP) is considered fatal unless treated promptly with the appropriate antiviral treatment. Various antiviral drugs have shown promising results in vitro. The mainstay of treatment at present is the nucleoside analogue GS-441524 and its prodrug remdesivir with multiple studies showing clinical efficacy ranging from 81.3 - 88.6% and no relapse for the responders up to one year after treatment. The nucleoside analogue molnupiravir has also been used with success. The protease inhibitor GC376 also appears effective in the injectable form, although oral effectiveness appears to be inferior to GS-4415249.
These antiviral treatments act quickly, with fever and other clinical signs often improving markedly within a few days, allowing the clinician to attempt trial treatment of cats in which FIP is very likely but cannot be confirmed. Most studies have used 84-day treatment courses, but evidence has now been published that shorter courses of 42 days may be equally effective for cats with effusions; such shorter courses will enable improved access to treatment for cost and/or compliance reasons.
Despite the significant progress in treatment that has happened over the last few years, FIP remains a challenging disease for the clinicians for several reasons:
1. It is often difficult to obtain a definitive diagnosis. Although effusive and non-effusive forms of FIP are described, there is much overlap between these forms and the clinical signs of FIP can change over time. Invasive diagnostic tests are often needed to secure diagnosis, but they carry a risk of the patient deteriorating.
2. The antiviral treatment is often expensive, not licensed and not available legally in many countries. Some countries have access to veterinary compounded antiviral products whereas others have access to antivirals developed for humans such as remdesivir or molnupiravir. In others, owners source antivirals themselves online, but the quality, purity, and concentration of active ingredients in these preparations is usually unknown, and can be variable, although they are often effective.
3. The ideal drug dose and duration of treatment is not certain yet. It is commonly believed that the neurological and ocular cases may need higher dosages due to the blood-brain and blood-ocular barriers.
4. Acute phase proteins are an integral part of treatment monitoring. Nevertheless, they are not specific for FIP and clear guidelines as to how they can guide treatment decisions are lacking.
5. Since the outbreak of feline infectious peritonitis (FIP) in Cyprus, caused by FCoV-23, a new combination of cat and dog coronaviruses, there is urgent need to understand modes of transmission and treatment options for "traditional" FIP versus FCoV-23, as new or similar outbreaks may occur world-wide.
Considering the challenges above, the upcoming lecture will further focus on clinical FIP case scenarios. The cases that will be presented will serve as a practical guide to diagnosis, treatment and monitoring that can help individualising drug dose and treatment duration on a case-basis. Furthermore, the attendant will gain an insight into novel monitoring tools that are expected to revolutionize FIP treatment soon, such as Therapeutic Drug Monitoring (TDM) and viral load assessment.
TDM involves measuring blood concentrations of the active metabolite of the antiviral drug, such as EIDD-1931 and GS-441524. This will allow for a greater understanding of how individual cats metabolise these drugs to avoid underdosing as a reason of treatment failure (because of poor absorption and/or rapid excretion in urine). Furthermore, certain antiviral drugs such as molnupiravir have been associated with dose-dependent toxicity and TDM will ensure that overdose is avoided. Optimising drug treatment should improve the prognosis for individual cats.
Viral load assessment involves measuring FCoV load by PCR with quantification in blood, faeces, fluid or tissue before, during and after treatment. This will show how quickly these drugs clear FCoV from blood and stools, helping to reduce new infections and to tailor the duration of treatment for the individual patient.
Πηγή: NEW AND OLD TREATMENT OPTIONS FOR FELINE INFECTIOUS PERITONITIS: INDIVIDUALISING TREATMENT
at https://fecava2024.org/wp-content/uploads/2024/09/Proceedings-Book-v05-1.pdf, σελ. 57-59
(29th FECAVA Eurocongress 2024 & 12o Eλληνικό Συνέδριο Κτηνιατρικής Ζώων Συντροφιάς E.K.E)
References:
1. Tasker S. GUIDELINE for Feline Infectious Peritonitis (Internet). ABCD European Advisory Board on Cat Diseases; 2024 Jun (cited 2024 July 26). Available from: https://www.abcdcatsvets.org/guideline-for-feline-infectious-peritonitis/
2. Barua S, Kaltenboeck B, Juan YC, Bird RC, Wang C. Comparative Evaluation of GS-441524, Teriflunomide, Ruxolitinib, Molnupiravir, Ritonavir, and Nirmatrelvir for In Vitro Antiviral Activity against Feline Infectious Peritonitis Virus. Vet Sci. 2023 Aug 9;10(8):513: https://doi.org/10.3390/vetsci10080513
3. Coggins SJ, Norris JM, Malik R, Govendir M, Hall EJ, Kimble B, Thompson MF. Outcomes of treatment of cats with feline infectious peritonitis using parenterally administered remdesivir, with or without transition to orally administered GS‐441524. Viruses. 2022 Nov 1;14(11):2429: https://doi.org/10.1111/jvim.16803
4. Taylor SS, Coggins S, Barker EN, et al. Retrospective study and outcome of 307 cats with feline infectious peritonitis treated with legally sourced veterinary compounded preparations of remdesivir and GS-441524 (2020-2022). J Feline Med Surg. 2023 Sep;25(9):1098612X231194460: https://doi.org/10.1177/1098612X231194460
5. Green J, Syme H, Tayler S. Thirty-two cats with effusive or non-effusive feline infectious peritonitis treated with a combination of remdesivir and GS-441524. J Vet Intern Med. 2023 Sep-Oct;37(5):1784-1793. DOI: 10.1111/jvim.16804
6. Zwicklbauer K, Krentz D, Bergmann M, et al. Long-term follow-up of cats in complete remission after treatment of feline infectious peritonitis with oral GS-441524. J Feline Med Surg. 2023 Aug;25(8): https://doi.org/10.1177/1098612X231183250
7. Sase O. Molnupiravir treatment of 18 cats with feline infectious peritonitis: A case series. J Vet Intern Med. 2023 Sep-Oct;37(5):1876-1880: https://doi.org/10.1111/jvim.16832
8. Roy M, Jacque N, Novicoff W, Li E, Negash R, Evans SJ. Unlicensed Molnupiravir is an Effective Rescue Treatment Following Failure of Unlicensed GS-441524-like Therapy for Cats with Suspected Feline Infectious Peritonitis. Pathogens. 2022 Oct 20;11(10):1209. DOI: 10.3390/pathogens11101209
9. Yan Y, Li J, Jiao Z, Yang M, Li L, Wang G, Chen Y, Li M, Shen Z, Shi Y, Peng G. Better therapeutic effect of oral administration of GS441524 compared to GC376. Veterinary Microbiology 2023. DOI: 10.1016/j.vetmic.2023.109781
10. Zuzzi-Krebitz AM, Buchta K, Bergmann M, Krentz D, Zwicklbauer K, Dorsch R, Wess G, Fischer A, Matiasek K, Hönl A, et al. Short Treatment of 42 Days with Oral GS-441524 Results in Equal Efficacy as the Recommended 84-Day Treatment in Cats Suffering from Feline Infectious Peritonitis with Effusion—A Prospective Randomized Controlled Study. Viruses 2024, 16, 1144: https://doi.org/10.3390/v16071144
11. Kent AM, Guan S, Jacque N, Novicoff W, Evans SJ. Unlicensed antiviral products used for the at-home treatment of feline infectious peritonitis contain GS-441524 at significantly different amounts than advertised. J Am Vet Med Assoc. 2024 Feb 7:1-9. DOI: 10.2460/javma.23.08.0466
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου