Tag: fip

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Control of enzootic infection with feline coronavirus in a closed environment with multiple cats and the disadvantages of using antivirals

Niels C. Pedersen DVM PhD, 7.4. 2024
Original article: Control of Enzootic Feline Coronavirus Infection in Closed Multi-Cat
Environments and Cons of Using Antivirals

When discussing feline coronavirus (FCoV) infection in a multicat setting, it is important to understand the correct nomenclature. The term FCoV is a collective term for two historically named viruses. A coronavirus was eventually identified as the causative agent of feline infectious peritonitis (FIP) in cats and named FIP virus or FIPV (Ward, 1970; Zook et al., 1968). FIPV was subsequently found to be a mutant form of FCoV that was present in cats infected with a widespread and minimally pathogenic enteric coronavirus and was named feline enteric coronavirus (FECV) (Pedersen et al., 1981). To avoid misunderstandings, this author prefers to refer to the form of FCoV that is relevant to the discussion at hand. Therefore, it is appropriate to use the term FIPV when discussing the form of FCoV found in a specific type of white blood cell (monocyte/macrophage) in the affected tissues and body fluids of cats with FIP. The term FECV is used to refer to the form of FCoV that causes chronic and intermittent infections of the epithelium in the lower intestine of healthy cats and is excreted in large quantities in the feces. Enzootic is the correct term for infections that are maintained at a low and variable level in animal populations, while endemic is the corresponding term used for humans. Epizootic refers to a sudden and significant outbreak of a new infection, usually with rapid direct spread to animals of all ages. The human equivalent of the term epizootic is epidemic. Clinical "signs" are what veterinarians and doctors observe on physical examination or what owners/parents communicate to them, while symptoms are what people recognize in themselves and tell their doctors about.

FECV, like other feline mucosal pathogens, is maintained in the population as a persistent or recurrent latent infection (ie, enzootic). FECV is first shed in faeces from around 9–10 weeks of life, coinciding with the loss of maternal immunity (Pedersen et al., 2008). Infection occurs via the faecal-oral route and targets the intestinal epithelium, and the primary symptoms of enteritis are mild or mild, transient and rarely chronic or severe (Pedersen et al., 2008; Vogel et al., 2010). Subsequent excretion of feces is from the large intestine and usually stops after several weeks or months (Herrewegh et al., 1997; Pedersen et al., 2008; Vogel et al., 2010) with the development of immunity. The resulting immunity is unfortunately short-lived and repeated infections are common (Pearson et al., 2016; Pedersen et al., 2008. A stronger immunity appears to develop over time and cats older than 3 years appear to be less prone to re-infection and become with faecal excreters (Addie et al., 2003).

FIP is caused by specific FECV mutants that develop during infection (Poland et al., 1996; Vennema et al., 1995).1 A final risk factor for FIP in multifeline settings is the proportion of cats with high titers of antibodies to feline coronavirus and shedding virus in feces (Foley et al., 1997). FIP-causing mutants develop in 10 % or more cases of FECV infection, but only a fraction of these eventually cause disease (Poland et al., 1996). The actual incidence of FIP in a population with enzootic FECV infection appears to range from about 1% to 10% cats, with cases occurring at unpredictable intervals and varying from individual cases to small groups (Addie et al., 1995b; Foley et al. , 1997). The actual incidence appears to be driven by multiple host and environmental factors that somehow compromise the immune system and increase the risk of FIP.1

Given the direct relationship between the presence of FECV and FIP, a logical way to prevent FIP would be to minimize exposure to FECV. A vaccine would be the simplest approach to control FECV infection, but no vaccine can produce better immunity than recovery from natural infection, as demonstrated by the SARS-CoV-II vaccine (Li et al., 2019). Based on what is known about the weakness and short-lived nature of natural immunity to FECV (Pearson et al., 2016; Pedersen et al., 2008), together with the considerable variation in serotypes and strains between different populations and regions (Addie et al., 1995b; Liu et al., 2019), it is unlikely that effective vaccines against FECV will be developed.

Although enzootic FECV infection cannot be easily prevented by vaccination, it is possible to eliminate FECV from a closed group of cats through thorough carrier testing and strict quarantine (Hickman et al., 1995). However, FECV is so ubiquitous in nature and easily spread through direct and indirect cat-to-cat contact and on human-borne fomites that the strictest quarantine facilities and procedures are required to stop it. How strict must the quarantine be? Experience with testing and removal in conjunction with quarantine to eliminate and prevent FECV infection is limited to one report (Hickman et al., 1995). FECV was eliminated from a specific pathogen-free breed of cats at UC Davis by removing the virus shedders and significantly tightening quarantine procedures for the remaining colony (Hickman et al., 1995). Nevertheless, FECV re-entered this colony after several years, despite all attempts to prevent its spread (Pedersen NC, UC Davis, unpublished, 2022). The only example of effective quarantine for FECV was described for cats in the Falkland Islands (Addie et al., 2012). These islands in the remote South Atlantic have fortunately remained free of FECV, probably due to their extreme isolation. Measures have been taken to prevent future inadvertent introduction of FECV to the islands (Addie et al., 2012). Based on this experience, it is unlikely that FECV could be kept out of any group of domesticated cats unless the strictest isolation and infection prevention practices are followed.

An interesting approach to prevent or delay FECV infection in kittens in kennels has been labeled "early weaning and isolation" (Addie et al., 1995a). This approach was based on the finding that kittens born to FECV-exposed or infected mothers acquired maternal immunity to infection up to 9 weeks of age (Pedersen et al., 2008). Therefore, kittens weaned a few weeks before the loss of this immunity (4-6 weeks of age) are usually free of infection and, if removed from the mother and isolated from other cats, could theoretically be kept free of the virus. This procedure was initially popular, but the facilities and quarantine procedures required to prevent the introduction of the virus are difficult to maintain in kennels with larger numbers of breeding cats (≥ 5 dams, Hartmann et al., 2005). Therefore, elimination of FECV in kittens by early weaning and isolation has been doomed to failure in most common homes/kennels due to ongoing direct and indirect exposure of infected cats to FECV. Another problem with early weaning and isolation is the need to separate virus-free kittens from other cats in a large group. This problem could be avoided if all the cats got rid of the infection at the same time. This can be achieved by serially testing faeces for FECV excretion over a period of time and culling all shedding cats along with strict quarantine. However, since a significant proportion of cats in farms involved in FECV enzootic disease shed feces (Foley et al., 1997; Herrewegh et al., 1997), elimination of cats can have a serious effect on the gene pool (Hickman et al., 1995). This begs the question – is there a way to eliminate FECV in all cats in a group at the same time?

Interestingly, the relatively recent discovery of effective antivirals against FIP (Pedersen et al., 2018, 2019) also provided a theoretical method to eliminate all shedding viruses at once. The first studies on such use of antivirals, although of a rather preliminary nature, suggested that FECV could be eliminated from a closed population of cats with relatively short treatment (Addie et al., 2023). Assuming that FECV can be eliminated as an enzootic virus from the feline population by using specific antivirals, what are the pitfalls of doing so? The first pitfall concerns the duration of immunity against reinfection that could be induced by a short course of antiviral treatment. A follow-up study of cats successfully treated for FIP with GS441524 showed a return of unremarkable FECV shedding in 5/18 individuals within 3 to 12 months (Zwicklbauer et al., 2023), suggesting that treatment, like recovery from natural infection, does not confer long-term immunity . Second pitfalls are the cost of antivirals to treat primary and secondary infections, frequent stool testing to monitor excretion, and establishing and maintaining adequate quarantine facilities and practices. Therefore, domestic facilities with poor barrier isolation practices are doomed to failure to maintain this group of cats FECV-free for extended periods of time. The third pitfall concerns the common activities associated with breeding and exhibiting breeding cats. Breeding cats involves frequent interaction between kittens and older cats, as well as between people who come into contact with the cats and with each other. It is also difficult to imagine that a breeder and avid show participant would give up all the joys of breeding and showing their cats by avoiding all such contact. The final question is - "now that the cats are free of FECV, what should be done with them?". What is the chance that they will remain without FECV for any length of time after leaving the controlled environment? They will have no immunity to FECV and will be very sensitive to the slightest exposure. The same will apply to the group of cats they come from. Finally, and this is the biggest concern, the constant antiviral treatment required to maintain a group of cats free of FECV infection will lead to the development of drug resistance. We now know that resistance to GS-441524 can occur in cats treated for FIP, and UC Davis researchers1 and Cornell University3 agree that acquisition of drug resistance in enzootic FECV infections would outweigh any potential benefit of such treatment on FIP incidence. FIP is currently curable in more than 90 % cases3, and even if resistance to antivirals does develop, it is largely confined to the affected cat. Arguably, HIV-1 infection in humans is currently prevented by antivirals, with no reported concerns about drug resistance. However, HIV-1 prevention treatment is not a monotherapy, but includes several drugs of different classes. Treatment with multiple drugs is not carried out with the aim of increasing the effectiveness of the treatment, but rather with the aim of preventing the development of drug resistance. If the virus develops resistance to one drug in the drug cocktail, the other drugs will prevent it from replicating.

In conclusion, I would like to paraphrase: "Just because something can be done, should it be done?" The author believes that much larger and better designed studies, conducted over a long period of time, are needed before treatment of asymptomatic FECV infection with antivirals can be seriously considered as a means of preventing FIP. The overall incidence of FIP in smaller and well-maintained breeding stations, shelters and research breeding colonies with FECV enzootic infection is often low and currently more than 90 % cases of FIP that could arise can be cured (Pedersen et al, 2019).3 A practical way to reduce the incidence of FIP is to keep the number of breeding cats and kittens low, to keep a larger number of older cats, not to breed individuals and bloodlines that have given rise to cases of FIP, and to minimize the stress of frequent introductions of new cats and placement/relocation .1 Isolation and early weaning can also be useful in smaller farms (Addie et al., 1995a). The problem of FIP in foster/rescue facilities is a bigger problem because most cats come from the feral population and are often very young when they arrive. They often suffer from malnutrition, a number of other diseases and are exposed to a high degree of stress associated with capture, routine treatment, change of diet, adaptation to a new environment and finally rehoming.1,3

References

  • Addie DD, Bellini F, Covell-Ritchie J, Crowe B, Curran S, Fosbery M, Hills S, Johnson E, Johnson C, Lloyd S, Jarrett O. 2023. Stopping Feline Coronavirus Shedding Prevents Feline Infectious Peritonitis. Viruses. 15(4), 818.
  • Addie DD, McDonald M, Audhuy S, Burr P, HollinsJ, Kovacic R, Lutz H, Luxton Z, Mazar S, Meli ML, 2012. Quarantine protects Falkland Islands (Malvinas) cats from feline coronavirus infection. J Feline Med Surg, 14, 171–176.
  • Addie DD, Schaap IA, Nicolson L, Jarrett O, 2003. Persistence and transmission of natural type I feline coronavirus infection. J Gen Virol. 84, 2735–2744.
  • Addie, D.; Jarrett, O. Control of feline coronavirus infections in breeding catteries by serotesting, isolation, and early weaning. 1995a. Feline Pract. 23, 92–95.
  • Addie DD, Toth S, Murray GD, Jarrett O. 1995b. Risk of feline infectious peritonitis in cats naturally infected with feline coronavirus. Am J Vet Res. 56, 429-34.
  • Foley JE, Poland A, Carlson J, Pedersen NC, 1997. Risk factors for feline infectious peritonitis among cats in multiple-cat environments with endemic feline enteric coronavirus. J Amer Vet Med Assoc. 210, 13131318.
  • Hartmann K, 2005. Feline infectious peritonitis Vet Clin North Am Small Anim Pract. 35(1), 39– 79.
  • Herrewegh AAPM, Mähler M, Hedrich HJ, Haagmans BL, Egberink HF, Horzinek MC, Rottier PJM, de Groot RJ, 1997. Persistence and evolution of feline coronavirus in a closed cat-breeding colony. Virology 234, 349–363.
  • Hickman MA, Morris JG, Rogers QR, Pedersen NC, 1995. Elimination of feline coronavirus infection from a large experimental specific pathogen-free cat breeding colony by serologic testing and isolation, Feline Practice 23, 96–102.
  • Li C, Liu Q, Kong F, Guo D, Zhai J, Su M, Sun D. 2019. Circulation and genetic diversity of Feline coronavirus type I and II from clinically healthy and FIP-suspected cats in China. Transbound Emerg Dis. 66, 763-775.
  • Pearson M, LaVoy A, Evans S, Vilander A, Webb C, Graham B, Musselman E, LeCureux J, VandeWoude S, Dean GA, 2019. Mucosal Immune Response to Feline Enteric Coronavirus Infection. Viruses 11, 906.
  • Pedersen NC, Theilen G, Keane MA, Fairbanks L, Mason T, Orser B, Che CH, Allison C, 1977. Studies of naturally transmitted feline leukemia virus infection. Am J Vet Res. 38, 1523–1531.
  • Pedersen NC, Boyle JF, Floyd K, Fudge A, Barker J, 1981. An enteric coronavirus infection of cats and its relationship to feline infectious peritonitis. Am J Vet Res. 42, 368-377. 5
  • Pedersen NC, Allen CE, Lyons LA, 2008. Pathogenesis of feline enteric coronavirus infection. J Feline Med Surg. 10, 529–541.
  • Pedersen NC, Liu H, Dodd KA, Pesavento PA, 2009. Significance of coronavirus mutants in feces and diseased tissues of cats suffering from feline infectious peritonitis. Viruses 1, 166-184.
  • Pedersen NC, Kim Y, Liu H, Galasiti Kankanamalage AC, Eckstrand C, Groutas WC, Bannasch M, Meadows JM, Chang KO, 2018. Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis. J Feline Med Surg. 20, 378-392.
  • Pedersen NC, Perron M, Bannasch M, Montgomery E, Murakami E, Liepnieks M, Liu H, 2019. Efficacy and
  • safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis. J Feline Med Surg. 21, 271-281.
  • Poland AM, Vennema H, Foley JE, Pedersen NC, 1996. Two related strains of feline infectious peritonitis virus isolated from immunocompromised cats infected with the feline enteric coronavirus. J Clin Microbiol. 34, 3180-3184.
  • Uusküla A, Pisarev H, Tisler A., et al., 2023. Risk of SARS-CoV-2 infection and hospitalization in individuals with natural, vaccine-induced and hybrid immunity: a retrospective population-based cohort study from Estonia. Sci Rep 13, 20347.
  • Vennema H, Poland A, Foley J, Pedersen NC, 1995. Feline infectious peritonitis viruses arise by mutation from endemic feline enteric coronaviruses. Virology 243, 150–157.
  • Vogel L, Van der Lubben M, , Te Lintelo EG, Bekker CPJ, Geerts T, Schuif LS, Grinwis GCM, Egberink HF, Rottier PJM, 2010. Pathogenic characteristics of persistent feline enteric coronavirus infection in cats. Vet Res. 41, 71.
  • Ward JM, 1970. Morphogenesis of a virus in cats with experimental feline infectious peritonitis. Virology 41, 191–194.
  • Zook BC, King NW, Robinson RL, McCombs HL, 1968. Ultrastructural evidence for the viral etiology of feline infectious peritonitis. Vet Path. 5, 91–95.
  • Zwicklbauer K, Krentz D, Hartmann K, et al., 2023. Long-term follow-up of cats in complete remission after treatment of feline infectious peritonitis with oral GS-441524. J Feline Med Surg. 25(8)

Footnotes

  1. Pedersen NC. History of Feline infectious Peritonitis 1963-2022 – First description to Successful Treatment. https://sockfip.org/wp-content/uploads/2022/04/Review-FIP-1963-2022-final-version.pdf4.29.22.pdf.
  2. Cornell University blog. Fight FIP. Unraveling feline infectious peritonitis from the ground up. https://blogs.cornell.edu/fightfip/fip-antivirals/.
  3. FIP Treatment – Czechia/Slovakia. https://docs.google.com/spreadsheets/d/e/2PACX-1vRAnj_FV_fteWIW1HXsROLuJ7YY1-i_Sf81BCmM9JT9LbCT2mcnwD1rL9IBsLCTB1U59CcnalOGjFqq/pubhtml?gid=1937250726&single=true
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Treatment of FIP in cats with Remdesivir

Original article: Treatment of FIP in cats with Remdesivir
Richard Malik DVSc PhD FACVSc FASM

Until recently, the diagnosis of FIP for a feline patient was a death sentence. Although omega-interferon and polyprenyl immunostimulant had some effects in some cases, most cats and kittens diagnosed with FIP died or euthanasia was required due to poor condition.

Figure 1. (A) BOVA Remdesivir reconstituted and ready for treatment. (B) The pathway that Remdesivir takes intracellularly to activate as GS-441524

That all changed a few years ago when the lifelong research of FIP Professor Niels C. Pedersen of UC Davis culminated. Niels first managed to save the lives of several cats with FIP with the protease inhibitor GC-376, and soon after showed that the nucleoside analog GS-441524 is even more effective in treating FIP, although the required dose depended on whether there was ocular or CNS involvement. . GS-441524 was a drug developed by the American company Gilead, which unfortunately did not show interest in further research into the molecule for veterinary use in the treatment of FIP. To fill the gap for effective FIP therapy, various companies have begun to manufacture GS-441524 and sell it on the black market. Although it was very expensive, the availability of quality GS-441524 provided determined cat owners with a way to save cats with wet or dry FIP, although obtaining this drug was complicated, usually associated with the help of a Facebook group. Unfortunately for cat lovers, APVMA and the Australian Veterinary Practitioner Board eventually made the import of GS-441524 and its use for veterinary purposes significantly more difficult, with repressive measures for veterinarians who wanted to help cats with FIP.

It is ironic that the COVID 19 pandemic has solved this problem. Gilead has developed remdesivir (GS-5734) for the treatment of human coronavirus disease. The drug received a temporary TGA marketing authorization in June 2020 for the treatment of SARS-Cov-2 infections in human patients. This process would normally take several years, but COVID accelerated it. Remdesivir is essentially GS-441524 with the addition of several additional phosphate groups to improve intracellular penetration (Figure 1B). Because remdesivir is an approved human drug, it can also be used off-label in veterinary practice, such as the treatment of FIP in cats. This circumvented problems with the use of an unlicensed medicine purchased on the black market and related problems with unproven efficacy, purity and consistency.

Figure 2. Dry FIP with pyogranulomatous inflammation of the intra-abdominal lymph nodes. Instead of exploratory laparotomy, lymph node biopsy, histology and immunohistology, it could be more cost-effective to try a 3-day intravenous Remdesivir treatment.

BOVA Aus was able to provide a reliable source of remdesivir. Studies in Australia have determined shelf life and confirmed in vitro efficacy against coronaviruses. We have been using it in clinical practice for the treatment of FIP for the last 6 weeks. Some of these cases were newly diagnosed cats, while others were cats that had already improved with GS-441524 obtained from the black market, which subsequently became unavailable. Several cases of wet and dry FIP have been treated. Even with the small number of cats, remdesivir appears to be very effective in treating FIP infections. Its subcutaneous administration is slightly easier compared to GS-441524, and it appears to be slightly less painful. It is supplied in a 100 mg vial, which is diluted with 9 ml of sterile water for injections to give a solution with a concentration of 10 mg / ml (10 ml vial after dilution).

In newly diagnosed cats with severe disease, we opted for the intravenous administration of remdesivir at a high starting dose (10 mg / kg dissolved in 10 ml saline and administered over 10 minutes) during the first 3 days of treatment, thus achieving a rapid onset of antiviral activity; The clinical signs of cats improved significantly during the initial therapy within 2-3 days. Cats then switch to subcutaneous treatment, usually at a lower dose. For common cases of FIP, we used 5-6 mg / kg once daily (SIUD) because remdesivir is thought to be approximately as effective as GS-441524 (Niels Pedersen, personal communication). In case of overt eye disease, a dose of 8 mg / kg SID is recommended and cats with neurological FIP with CNS symptoms are given 10 mg / kg SID. Treatment is then continued by daily subcutaneous injections for another 2-3 months. In cats for which SC injections were painful, we used gabapentin and / or buprenorphine for sedation / analgesia, and in some cases we introduced a new cephalic catheter every 5 days, which allowed the owners intravenous administration. In situations where owners could not afford the entire treatment, or when the injections were too painful, we used mefloquine (62.5 mg 2-3 times a week; obtained from BOVA or a local pharmacy) for initial work-based antiviral treatment after initial treatment with Remdesivir. Jacqui Norrisa and colleagues from the University of Sydney.

Figure 3. Which cat has FIP and is being treated with remdesivir?

The main advantage of FIP Remdesivir treatment is that the active substance we use is present in an approved medicine for human use. It is just a matter of writing a prescription with the name and address of the client, the name of the patient and the dose to be administered. BOVA can usually prepare and deliver vials to any veterinarian in Australia within 24-48 hours. At present, the cost per 100mg vial is $ 250 plus GST and postage, although it is possible that the price will decrease over time due to larger orders. We believe that most owners will feel much better if they get the product from a well-known Australian company than to send money abroad and hope that black market drugs will get safely from China to Australia.

Veterinarians who want to know more about this treatment option or have general questions about FIP can contact me by email (richard.malik@sydney.edu.au). The diagnosis of FIP is beyond the scope of this newsletter, but effusive cats are most easily diagnosed by cytology and effusion analysis, followed by immunohistochemistry at VPDS, University of Sydney (easily arranged via Vetnostics, QML, ASAP, VetPath, Gribbles or IDEXX). Dry FIP is more problematic because it usually requires an accurate aspiration biopsy of pyogranulomatous lesions in the liver, kidneys, or abdominal lymph nodes. We found that 3 days of intravenous Remdesivir therapy could be used as a cost-effective therapeutic test in cats with dry FIP as an alternative to biopsy of intra-abdominal structures in exploratory laparotomy, as FIP cases rapidly improve most clinical symptoms. If veterinarians do not want to start treatment with Remdesivir themselves, we can recommend veterinarians interested in FIP treatment who would like to accept such cases.

Resources

Kim, Y .; Liu, H .; Galasiti Kankanamalage, AC; Weerasekara, S .; Hua, DH; Groutas, WC; Chang, KO; Pedersen, NC Reversal of the progression of fatal coronavirus infection in cats by a broad-spectrum coronavirus protease inhibitor. PLoS Pathog. 2016, 12, e1005531.

Pedersen, NC; Kim, Y .; Liu, H .; Galasiti Kankanamalage, AC; Eckstrand, C .; Groutas, WC; Bannasch, M .; Meadows, JM; Chang, KO Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis. J. Feline Med. Surg. 2018, 20, 378–392.

Murphy, BG; Perron, M .; Murakami, E .; Bauer, K .; Park, Y .; Eckstrand, C .; Liepnieks, M .; Pedersen, NC The nucleoside analog GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies. Vet. Microbiol. 2018, 219, 226–233.

Pedersen, NC; Perron, M .; Bannasch, M .; Montgomery, E .; Murakami, E .; Liepnieks, M .; Liu, H. Efficacy, and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis. J. Feline Med. Surg. 2019, 21, 271–281

Dickinson PJ, Bannasch M, Thomasy SM, et al. Antiviral treatment using the adenosine nucleoside analogue GS-441524 in cats with clinically diagnosed neurological feline infectious peritonitis. Journal of Veterinary Internal Medicine. 2020. doi: 10.1111 / jvim.15780.

McDonagh, P .; Sheehy, PA; Norris, JM Identification and characterization of small molecule inhibitors of feline coronavirus replication. Vet. Microbiol. 2014, 174, 438–447.

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Thanks to COVID, veterinarians can now legally treat FIP in cats

Original article published on walkervillevet.com.au, 24.11.2020.

The nightmare is almost over. Until recently, there was a diagnosis infectious peritonitis in cats death sentence. Either a slow, persistent decline, or a decision to euthanize and end suffering. This happened to about 1% cats, mostly still kittens.

It was later found that certain antiviral drugs they can not only improve the symptoms, but can even lead to cure. But there was still a problem.

These antivirals were not licensed in Australia and therefore their import and use were illegal. The only cats that survived were therefore those whose owners and veterinarians were willing to take risks. My own veterinary association despite evidence of treatment effectiveness strongly warned against using them.

All the problems are over today.

Remdesivir: A new hope for the FIP

You must have heard of remdesivir. It was promptly approved by the TGA and the FDA due to promising results in the treatment of COVID-19. Importantly for remdesivire is that it is almost identical to black market drugs such as GS-441524.

It is now freely available with a valid prescription and meets all the strict criteria we expect from licensed drugs. Veterinarians still need to warn you that this is an off-label treatment, but it is the same as other cases where we use a human drug for treatment (which is often the case!).

Preliminary testing in Sydney has yielded excellent results. So now we have a cure for everyone. I estimate that fewer than 5% cats with FIP are currently undergoing treatment. Now all cat owners are offered a chance for treatment and most will seize it, although the cost problem still exists.

The cost of using remdesivir in cats

As you can imagine, it is an expensive medicine. I estimate that the 80-day treatment will cost around $ 4,800.

Is a however, this is very similar to the prices people currently pay for GS-441524 from the black market with unproven purity or efficiency. This time, if the cat is insured, it is likely that the treatment will even be covered by the insurance company.

Based on our previous observations, 84-day treatment should cure most affected cats. It is given as a subcutaneous injection once a day, but don't be put off. Everyone can do it and we will be happy to show you how.

Advice on the use of remdesivir for veterinarians

Australian veterinarians reading this article can contact me about a document that contains the recommended dosage, protocols based on the symptoms of the disease and how to obtain the drug itself. See the comments section below for some dosing notes. (translator's note - click on the link leading to the original article).

We are all committed to the work of Dr. Richard Malik DVSc PhD FACVSc FASM and the Feline Diseases Research Team at my alma mater The University Of Sydney.

We also thank the volunteer groups that helped many cats regain their health by taking risks. Their work is complete and we are grateful.

Andrew Spanner BVSc (Hons) MVetStud, a veterinarian in Adelaide, Australia. These blogs come from a series of regularly published e-mails and  Twitter.
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History of FIP research

Original article: History of FIP research; 19.10.2010; Translation 1.2.2021

Probably the oldest recorded case of FIP (Utrecht State Veterinary School, 1912/13); retrospective diagnosis is likely from the description of chronic exudative peritonitis, dyspnoea (pleurisy?), fever and eye symptoms. (Jacob, 1914).

The sudden occurrence of FIP in the late 1950s has been documented in long-term and thorough autopsy records at the hospital. Angell Memorial Animal Hospital in Boston. Therefore, the existence of FIP as a major disease before this time is questionable. The mention of a cat with a disease reminiscent of the FIP was published half a century earlier (1914 Jakob-Groot and Horzinek), but whether it was really the FIP is uncertain given the absence of reports of a similar disease in the following decades. The incidence of the disease has steadily increased since the 1960s and is currently one of the leading infectious causes of death in young cats from shelters and kennels. The reason for the sudden onset of FIP is unknown, but there are at least three possible explanations. First, coronaviruses may have specialized in cats over the last half century. Remarkably, FIP emerged ten years after the first mentions of porcine gastroenteritis (TGE) in North America. The causative FIP virus is closely related to porcine TGE virus and CCV (Canine Corona Virus), although they are still genetically distinguishable. However, recombinants are known to occur between these three viruses. At least one CCV strain can cause mild enteritis in cats and exacerbate subsequent FIPV infection, suggesting a strong resemblance to feline coronaviruses. Therefore, in this scenario, CCV may be a more likely precursor to FECV. Recombinant events are favored by the ease with which transcription units (RNAs) can be gained or lost during the divergent development of coronaviruses. Second, the FIP mutation may be selective for the FECV variant that emerged in the 1950s. This variant could also arise due to intraspecific and interspecific mutability of coronaviruses in general, and in this case FCoV in particular. The third explanation may include changes in the understanding of cats as pets and their breeding in this modern age. After World War II, there was a dramatic shift when cats began to behave like pets. The numbers of domestic cats have increased significantly, the breeding of purebred animals and cat breeding has become more popular, and more and more cats, especially kittens, have found themselves in shelters. These large, multi-cat enclosures are known to be a breeding ground for feline enteric coronavirus (FECV) and FIP infection. Interestingly, feline leukemia virus infection also spread among domestic cats during this period. FeLV infection was an important cofactor for FIP until it was pushed back into the wild in the 1970s and 1980s by testing, elimination / isolation, and possible vaccination.

Genetic relationships between different genotypes of feline and canine coronaviruses (FCoV and CCoV). Feline sequences are colored blue, canine sequences are colored orange, and porcine sequences are colored purple. Arrows indicate predicted recombination sites. Genes encoding polymerase polyprotein (Pol), structural peak (S), envelope (E), membrane (M) and nucleocapsid (N) proteins are indicated. Genes encoding helper proteins are indicated by numbers.

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