A serious cat disease

Feline Infectious Peritonitis (FIP)

What is FIP?

Nervous CatFeline infectious peritonitis (FIP) is a serious disease in cats caused by a mutation of the common feline enteric (gut) coronavirus (FeCoV). The mutation allows the otherwise insignificant virus to enter to escape the gastrointestinal tract lining by entering the gut macrophage cells (an immune system cell) and hitching a ride to other parts of the body, infecting the abdominal cavity, chest cavity, eyes and in some instances, the brain. Usually, a cat’s immune system prevents clinical FIP but in some cats infected with enteric FeCoV, the immune system fails to eliminate the infection and clinical FIP develops with devastating consequences.

Over 30% of pet cats and over 80% of breeding cats have been exposed to FeCoV (the relatively harmless enteric form).

While the relatively harmless enteric coronavirus (FeCoV) is highly transmissible between cats, the mutated form FIP itself is not contagious to other cats and the feline coronavirus is not the same as the human coronavirus that causes COVID-19.

Clinical signs of FIP

Cats with clinical FIP develop a range of clinical signs such as:

  • Fever unresponsive to antibiotics
  • Fluid in the abdominal and/or chest cavities
  • Palpable enlarged abdominal lymph nodes
  • Change in the symmetry of the pupils or eye colour
  • Neurological signs (brain infection)

The clinical signs depend on whether the cat has the effusive or ‘wet’ form of FIP or non-effusive or ‘dry’ form of FIP, although more often than not, there is a combination of wet and dry forms present, known as a ‘mixed wet and dry’ FIP.

Dry FIP is typically much harder to diagnose as there is no obvious fluid-filled body cavity to sample from and instead pyogranulomas form either in a focal spot (e.g. intestine or kidney), or multiple sites (e.g. abdominal cavity, brain).

Cats at risk of FIP

The majority of cats that develop FIP affected are young between 3 months and 2 years of age (80%), or elderly cats, and the disease often affects purebred cats, especially the following breeds: Ragdolls, Abyssinians, Bengals, British Short Hairs, Exotics, Devon Rex, Birmans.

Interesting, the purebreds that are less commonly represented are Siamese, Persian and Himalayan cats.

Cats that have been housed together in a rescue facility where multiple cats share a litter tray are also at a higher risk of developing FIP.

FIP is more common in male cats, with a male to female ratio of 2:1.

Any cat that has previously been exposed to enteric feline coronavirus can potentially develop FIP, but in the vast majority of cats, the enteric coronavirus is insignificant and does not require any treatment.

Diagnosis of FIP

Laboratory changes on blood work typical of FIP may include:

  • Hyperglobulinaemia (elevated globulins)
  • Non-regenerative anaemia (low red blood cell count)
  • Neutrophilic leukocytosis (elevated white blood cell count)
  • Elevated liver parameters (ALT, ALP, elevated bilirubin)

An albumin to globulin ratio of < 0.8 raises the suspicion of FIP in a young cat. It’s important to note that no single laboratory abnormality will occur 100% of the time. If the albumin to globulin ratio is < 0.4 then there is a > 90% likelihood that the diagnosis is FIP.

Fluid analysis for cases of ‘wet’ FIP typical changes include:

  • Specific gravity of 1.017-1.047
  • Protein > 35g/L in all cases
  • Low cellularity (< 20 000 cells/ml) containing mainly non-degenerate neutrophils and macrophages

For a definitive diagnosis of FIP the following tests can be used:

  • Direct Immunofluorescence (IFA) for FIP antigen in body cavity fluid sample in ‘wet’ FIP cases (not blood) (available through Vetnostics or Veterinary Diagnostic Pathology Services (VDPS) which has a > 99% specificity and 75% sensitivity for FIP
  • FIP PCR on fluid sample (‘wet’ FIP) (available through IDEXX laboratories)
  • Immunohistochemistry or immunocytochemistry from an FNA or biopsy sample from an enlarged lymph node (‘wet’ or ‘dry’ forms)
  • Brain MRI and/or CSF tap (‘dry’ FIP)

Co-morbidities such as toxoplasmosis and/or mycoplasmosis (if anaemic) could be present, so ruling out these diseases via toxoplasma titres (IgG and IgM) and a Mycoplasma PCR test is helpful. Testing for FIV and FeLV is recommended.

False negatives are common, so if a definitive diagnosis of FIP cannot be obtained, or the owner has financial constraints, then a remdesivir treatment trial can be considered. Usually, FIP cats respond rapidly to remdesivir, with fever resolving and significant improvement noticed within 3-5 days of starting treatment, sometimes as early as 24 hours after the first injection.

Faecal sample

Due to the fact that so many healthy cats carry feline coronavirus (FeCoV) with very little consequence (except for diarrhoea in some cases), obtaining a faecal PCR test that returns a positive coronavirus sample is unhelpful in supporting a diagnosis of FIP.

Blood serology

The feline coronavirus antibody test is generally unhelpful, as cats can have a high titre due to exposure to feline coronavirus but not necessarily have FIP, but more importantly, if negative, FIP still cannot be ruled out.

Dr Gretta Howard's interest in FIP

As a new graduate vet in the year 2000, Dr Gretta had to deliver very sad news to a young family with their beautiful new kitten who had developed FIP. The kitten had a very swollen abdomen full of fluid, a high fever and breathing problems. Unfortunately, at this time, there was no treatment available and as the cat was suffering, euthanasia was the only option.

18 years later, Dr Gretta first heard about GS-441524, a new anti-viral FIP treatment, when she attended a lecture about its discovery at an Australian and New Zealand College of Veterinary Scientists conference in Queensland in 2018.

Dr Gretta has always had an interest in infectious diseases and as a side-project during the first COVID-19 Sydney lockdown, Dr Gretta started volunteering as a veterinarian with the FIP Warriors Facebook group and via email, communicating with vets and owners located all over the world, including USA, Europe, Russia, South America, Middle East, Asia and home in Australia, to assist remotely in the management of their FIP cases. Through this rewarding, yet challenging experience, Gretta has collaborated with many other veterinarians and cat rescue groups who treat vast numbers of FIP cases.

Remdesivir and FIP

Remdesivir (GS-5734 trade name Veklury, Gilead Sciences) was approved in 2020 as an anti-viral protease inhibitor for use in COVID-19 patients. Remdesivir is actually the prodrug for GS-441524 (which means remdesivir is metabolised into GS-441524 once in the body), but unfortunately, Gilead was not interested in pursuing the feline market for this drug.

In 2020, BOVA Animal Compounding Pharmacy secured a supply of remdesivir, which means that vets can write a script to acquire it for their patients. If the pharmacy supplies the medication via a veterinary script, it is not the vet supplying the drug. This avoids cat owners attempting to illegally import an unlabelled, unregistered drug and deal with the consequences if caught by the authorities. Prior to remdesivir being available to veterinarians, this was the only option for clients who wished to treat their FIP positive cats, and as it is illegal for vets to import unregistered medications, owners were left to source medication and learn how to inject their cats themselves without veterinary guidance.

Dr Gretta Howard’s friend and colleague, one of the world’s most well-known and respected feline specialistsDr Richard Malik, has been instrumental in volunteering his time and expertise helping vets treat sick cats world-wide and in conjunction with other FIP researchers, has put together a FIP remdesivir treatment protocol for veterinarians. This gives vets a much better way to effectively treat FIP patients while they remain under their care and is therefore a much better overall outcome for the welfare of cats with this horrible disease, which was previously a death sentence.

Treatment protocol for FIP cats with remdesivir

Dr Gretta Howard co-authored an article in The Veterinarian: “Treatment of FIP in cats with remdesivir” with Dr Richard Malik and Dr David Hughes, which discusses the protocol for FIP treatment with remdesivir. Since this article was published, dose recommendations for remdesivir have been increased. Dr David Hughes and Dr Rebecca Brady published an article with updated dose rates in Control & Therapy (Centre for Veterinary Education): “A feline infectious peritonitis treatment protocol”. These resources are available on this page.

As this is still in experimental stages, these treatment protocols will be subject to change and refined over time as more cats are treated successfully, so it is important to obtain the most current recommendations that have been based on research findings.

Remdesivir veterinary prescription to BOVA Animal Compounding Pharmacy

In NSW, while it is acceptable to charge a script fee, it is illegal for vets to place a mark-up on compounded medication from pharmacies. At Turramurra Veterinary Hospital, the script is emailed (and then the hard-copy posted) to BOVA then once received, clients can make a direct payment to BOVA for the medication, which is then delivered to the vet hospital within 24-48 hours. Scripts for remdesivir are marked URGENT for remdesivir for priority post. It is recommended for critical cases, that the script is email and paid for prior to 3pm so that vials can be posted to the vet clinic on the same day.

Remdesivir dose recommendations for FIP treatment

Dose recommendations continue to evolve over time as further research is pursued and more cases are treated with remdesivir.

Dose recommendations (updated Nov 2021):

Effusive ‘wet’ FIP                    10mg/kg once daily by subcutaneous injection

Non-effusive ‘dry’ FIP            15mg/kg once daily by subcutaneous injection

Ocular FIP                               12mg/kg once daily by subcutaneous injection

Note: any case that has neurological signs is considered a non-effusive ‘dry’ FIP case, as often cases can be ‘mixed’ FIP with signs of both wet and dry FIP. These should be treated at the higher dose of 15mg/kg.

If patients are critically ill, then an intravenous protocol can be used for the first 3 days using an initial dose of 10-15mg/kg once daily while the cat is hospitalised on intravenous fluids. It is critical to monitor these cases closely for the development or worsening of pleural effusion (fluid in the chest).

Cats that start their FIP treatment with remdesivir injections generally improve within the first week of starting treatment. If this does not occur, then it is better to seek further diagnostics (if FIP has not been definitively diagnosed).

Generally, we recommend continuing treatment for 12 weeks (84 days) then stop if the cat is doing clinically well and the blood results look promising. The dose of remdesivir in kittens should be recalculated on a weekly basis upwards as they grow to prevent underdosing.

An increase in dose and/or extension of the course of treatment may be recommended based on the clinical response to therapy, blood parameters or signs of relapse.

Cost of Remdesivir

BOVA sourced remdesivir is $280 per 100mg vial.

Treating a 2.5kg cat with effusive FIP for 12 weeks with remdesivir (25mg per day or 2.5ml) requires approximately 21 vials so costs approximately $6000.

Note: costs do not include veterinary consultations, additional medications if required or blood test monitoring.

The cost of treatment is expensive, and it is important to note that many cats with FIP have been cured at much lower doses, such as 5-6mg/kg once daily by subcutaneous injection, so if clients cannot afford the higher doses, a lower dose for a shorter duration is better than no dose.

I routinely recommend mefloquine to be used in conjunction with remdesivir to reduce the chance of a relapse (see below for information on timing, dose and duration).

GS-441524 tablets for FIP treatment

More recently, BOVA has been able to source GS-441524 tablets (50mg quarter-scored), which are an alternative option for cats that do not tolerate the injections or for owners unable to administer them. ​Due to the variability between individuals of oral treatment absorption, particularly while cats are unwell, starting FIP cases on injections for at least 2 weeks until they are clinically normal tends to result in a better overall response and a lower likelihood of a relapse once treatment is stopped. Generally both remdesivir and GS-441524 tablets have a high safety profile in cats.

Generally, we recommend continuing treatment for 12 weeks (84 days) then stop if the cat is doing clinically well and the blood results look promising. The dose of GS-441524 tablets in kittens should be recalculated on a weekly basis upwards as they grow to prevent underdosing.

Cats that start their FIP treatment with the oral GS-441524 tablets generally improve within the first week of starting treatment. If this does not occur, then it is better to seek further diagnostics (if FIP has not been definitively diagnosed) or switch to injections, in case the problem is relating to intestinal absorption.

Dose recommendations (updated Nov 2021):

Effusive ‘wet’ FIP                    8-10mg/kg once daily orally

Non-effusive ‘dry’ FIP            12-15mg/kg once daily orally

Ocular FIP                               12mg/kg once daily by orally

There is a general consensus that GS-441524 tablets should be given at least an hour before food, as they are absorbed better on an empty stomach.

Cost of GS-441524 tablets

BOVA sourced GS-441524 tablets cost $600 for 10 x 50mg tablets currently (updated Nov 2021). Treating a 2.5kg cat with effusive FIP for 12 weeks with GS-441524 (25mg per day or HALF a 50mg tablet) requires approximately 42 tablets so costs approximately $2500.

Note: costs do not include veterinary consultations, additional medications if required or blood test monitoring.

I routinely recommend mefloquine to be used in conjunction with GS-441524 to reduce the chance of a relapse (see below for information on timing, dose and duration).

Mefloquine orally in FIP treatment

In addition to remdesivir, the human anti-malerial drug, mefloquine (Larium), can be used orally at a dose rate of 10-12mg/kg orally twice a week with food (eg Wednesdays and Sundays). For an average sized cat, this is approximately ¼ x 250mg tablet. For smaller cats < 5kg, I would recommend ordering this medication through BOVA animal compounding, to ensure the dose is correct.

Some cats do not tolerate mefloquine (vomiting, inappetence), so it is important that cats are eating well prior to starting mefloquine, so that it is obvious if they are having a side effect.

Mefloquine’s mechanism of action is suspected to be preventing the virus from entering macrophage cells (inhibition of endocytosis).

Dr Gretta recommends starting this once the cat is stable on remdesivir or oral GS-441524 therapy, then continuing to use mefloquine for 3 months beyond stopping remdesivir or oral GS-441524 therapy. Clinically stable refers to a resolution of overt signs of FIP and that the cat is eating well. There is some evidence to suggest that this protocol reduces the chance of a relapse as it buys the body some time to allow the cat’s immune system to figure out how to get rid any remaining virus.

Note: The life-span of a macrophage cell is 2 months, so it could be argued that mefloquine treatment should continue for a minimum of 2 months total if tolerated. I personally prefer a longer mefloquine treatment protocol.

Mefloquine is metabolised by the liver, so monitoring liver parameters is helpful if the owner’s finances allow for this.

If owners cannot afford remdesivir or oral GS-441524 tablets, then mefloquine alone can be used as a sole therapy and in some cases, treatment can be successful, so it is worthwhile trying mefloquine in these patients, or using it after an initial shorter course of remdesivir or GS-441524, as mefloquine can buy the cat some time so that their own immune system can work out how to fight FIP.

Molnupivavir - a new anti-viral drug

Molnupivavir is a new anti-viral, manufactured by MSD, that is showing promise as a treatment option for FIP, but this drug is not yet available in Australia. An article by Dr Niels Pedersen is available on this page: “The long history of Beta-D-N4-Hydroxycytidine and its modern application to treatment of COVID-19 in people and FIP in cats”.

Monitoring

Monitoring is recommended every 4 weeks until the end of the 12-week treatment period, however, if the cat is doing well on remdesivir therapy, and the owner has financial constraints, then less frequent reassessments may be recommended. Monitoring recommendations vary from patient to patient.

A steady improvement in the albumin to globulin ratio is one of the markers to look for when determining response to therapy. The only problem with this approach, is that we rarely have a pre-FIP albumin to globulin ratio to compare to, so we never really know what a specific individual’s normal levels are. Another positive indicator is seeing the lymphocytes at > 30% on a haematology sample.

It’s vital to treat the patient and not just the laboratory values, because there is no one marker that determines whether a patient is cured.

Treating veterinarians must use their best judgement based on clinical response to treatment, laboratory values and the owner’s financial constraints to make decisions about dose increases and extensions and when to discontinue treatment.

Pet health insurance cover

If your cat was healthy at the time of taking out pet insurance cover, then your insurance company may cover the cost for FIP treatment. Approval is on a case-by-case basis and subject to review. If you have pet insurance cover for your cat but your claim has been declined, then ask your vet to phone the insurance company’s vet help line to have the claim reviewed. This has sometimes resulted in an overturn on a decision to deny a claim, resulting in a client being able to claim the costs for FIP treatment.

Many drugs used in veterinary medicine, including remdesivir, are not APVMA approved, but are approved by the Australian Register of Therapeutic Goods (ARTG). Given research and journal articles supporting remdesivir as a proven FIP treatment, if your vet prescribes remdesivir for FIP treatment, then it is recommended to submit an insurance claim for consultations and treatment costs. ​

FIP face-to-face or telehealth consultations with Dr Gretta Howard

Dr Gretta Howard is available for face-to-face (pending COVID restrictions) or telehealth consultations for cat owners based in NSW who wish to seek her opinion on FIP case management. In addition to a consultation, this involves reviewing any prior veterinary records, laboratory results and management recommendations. Consultations (face-to-face or telehealth) are $159 and subsequent reassessment is $99, payable over the phone at the time of booking your appointment. Written prescriptions are an additional $39.50 per medicine prescribed.

If you would like to go ahead with a consultation, please phone our customer care team on (02) 9988-0198 so they can book you in with Dr Gretta Howard at a suitable time. Please ensure to include an update on whether your cat is critically ill or stable (eating, comfortable) so that priority can be given to very sick cats.

Once booked in, please forward your previous veterinary records, laboratory results and a summary of your own via email to our reception team, including your cat’s current weight. Where possible, these records can be reviewed prior to the appointment time.

Unfortunately, due to NSW veterinary board regulations, Dr Gretta Howard is unable to provide consultations outside of NSW but may be able to provide you with the names of vets comfortable treating FIP in your Australian state so that you can arrange an appointment with them. Your vet is welcome to email questions regarding case management to Dr Gretta Howard for further assistance on FIP case management if required.

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