FCoV Infection and FIP

Question 1

1. % FCoV seropositive cats in multicat households.
2. % FCoV-infected cats w/ FIP?

Answer 1

1. 80-100%
2. 1-5%.

Question 2

1. What are FCoVs?

Answer 2

1. Large enveloped RNA viruses.
   – susceptible to disinfectants.
   Replication of RNA genomes prone to mistakes – mutations.
   –> can allow virus to get into the WBCs (monocytes) and replicate aggressively and cause FIP. The cat’s environment contributes too.

Question 3

Host factors affecting the development of FIP.

Answer 3

Age – young cats most affected, esp. <2yrs old.
Sex – slight increase in male compared to female.
Immune response – strong humoral response –> T cell depletion –> increased risk of FIP.
Breed/genetics – different from country to country due to diff. breeding lines.

Question 4

Environmental factors affecting FIP development.

Answer 4

• Level of stress e.g. overcrowding.
• Number of cats in household.
• Degree of FCoV exposure –> increased risk of FIP.

Question 5

How common are FCoVs?

Answer 5

1. Seropositivity in 25-40% household pets.
2. 80-100% cats in multi-cat households.
   – A proportion of seropositive cats shed FCoV in faeces.

Question 6

Is FCoV serology likely to be useful in the diagnosis of FIP?

Answer 6

No.
Lots of cats infected w/ FCoV and only a small proportion have FIP.
No antibody test for FIP virus because FIP viruses have differences.

Question 7

Transmission of FCoVs.

Answer 7

Faecal FCoV shedding within 1 week of oral infection.
Faecal oral transmission.
Fragile – destroyed by most disinfectants (incl. bleach) but can survive in faecal matter so cleaning is important.
Kittens acquire maternal derived immunity in colostrum from their mum/queen.
– lasts 6-8wks but then kittens become infected w/ FCoVs and then shed in the faeces.

Question 8

Outcome of FCoV infection.

Answer 8

• Transient FCoV infection.
  – occurs in most cats –> FCoV shed in faeces for a few months then eliminated but cats are then susceptible to reinfection w/ FCoV because immunity to infection is only short term (few weeks).
• Development of FIP.
  – Small % of cats develop FIP.
  – There are viral, host and environmental factors that cause mutations that can lead to FIP.

Question 9

What are the 2 types of clinical disease of FIP?
Which is most common?

Answer 9

• Effusive/Wet FIP – vasculitis and non-septic exudates. — most common.
• Non-effusive/Dry FIP – (pyo)granulomatous lesions in tissues.
  *overlap between these.

Question 10

1. Duration of effusive/wet FIP progression?
2. Where do the effusions occur?
3. What is it important to look for in the abdomen?
4. Non-specific signs of effusive/wet FIP?
5. More specific clinical signs?
6. What imaging can be used?

Answer 10

1. Weeks.
2. Abdomen and pleura – but abdomen more so –> can also get it in the pericardium and the scrotal space.
3. Masses – visceral / omental adhesions, mesenteric LNs up.
4. Fever (non-responsive), anorexia, lethargy, weight loss, jaundice.
5. Abdominal effusion – abdominal distension.
   Pleural effusion – dyspnoea, tachypnoea.
   Pericardial effusion.
   Scrotal swelling.
6. Ultrasound – look for free fluid.

Question 11

1. What is seen on PME of cat that was infected w/ FIP?

Answer 11

1. Highly proteinaceous effusion w/ fibrin deposits throughout the abdomen.
   May have yellow thick abdominal effusion around intestines.
   Large round granulomas visible on intestinal surface. – typical of dry form but often seen in wet form also.

Question 12

1. Duration of disease course of non-effusive/dry FIP.
2. Specific signs.
3. Non-specific signs.

Answer 12

1. More chronic disease course – can be months.
2. Ocular (e.g. uveitis) or neurological signs in 45%.
   Renomegaly/irregular kidneys – granulomas (associated w/ vasculature).
   Mesenteric LNs up.
3. Fever (non-responsive), anorexia, lethargy, weight loss, jaundice.

Question 13

More ocular signs of dry/non-effusive FIP?

Answer 13

Iritis, corneal oedema, dyscoria/anisocoria, loss of vision, hyphaema, hypopyon, keratic precipitates, aqueous flare, perivascular cuffing, chorioretinitis.

**cross reference to ophthalmology lectures to come.

Question 14

More neurological signs of dry/non-effusive FIP?

Answer 14

Ataxia, head tilt, hyperaesthesia, nystagmus, seizures.

Question 15

What do we need to confirm a diagnosis of FIP?

Answer 15

• Histopathology of affected tissue w/ immunostaining of FCoV antigen (immunohistochemistry).
• Effusion or FNA cytology w/ immunostaining of FCoV antigen (immunocytochemistry) also useful.

Question 16

What other info helps work towards a diagnosis of FIP?

Answer 16

• Historical factors – youth, household, stress, breed/genetics.
• Clinical signs – Signs of effusive and/or non-effusive disease, progressive (re-examine sequentially), neuro exam, ophthalmic exam, imaging (chest and abdomen to look for free fluid (can use this for cytology).

Question 17

Blood sampling for diagnosis of FIP.

Answer 17

Haematology – lymphopenia, neutrophilia and/or mild left shift, anaemia.
Biochemistry – Hyperproteinaemia –> polyclonal increase in globulins usually w/ low or low-normal albumin.
– low albumin : globulin ratio (<0.4).
– Very increased a1 glycoprotein AGP = acute phase protein.
– Hyperbilirubinaemia (may be jaundiced).
– +/- high liver enzymes – often not hugely compared to liver disease.

Question 18

Effusion inspection and biochemistry.

Answer 18

• Often viscous, yellow.
• Protein > 35g/L.
• Globulins > 50%.
• Low albumin : globulin ratio (<0.4).
• High AGP.
• Poor cellularity, usually < 5 x 10^9/L cells.
• Immunostaining for FCoV antigen.

Question 19

How do you look for FCoV RNA?
What about tests that look for specific mutations in FCoV spike protein gene that are associated w/ FIP?

Answer 19

Reverse- transcriptase PCR.
On effusions and FNAs from affected tissues (imaging) to help diagnose FIP.
High levels of FCoV RNA are consistent w/ FIP.
Not more specific that reverse-transcriptase PCR as spike protein mutations likely show presence of systemic FCoV compared to a FCoV definitely causing FIP and many different types of mutation are likely to be involved.

Question 20

Treatment of FIP.

Answer 20

• 5yrs ago, no effective treatments available so options were: -
  – Supportive treatment e.g. drain pleural effusions if dyspnoea and usually no benefit in draining abdominal effusions.
  – Interferon treatment w/ no proven benefit.
  – Polyprenyl immunostimulant – stimulates immune system.
  –> upregulates Th-1 cytokines.
  –> May be of some benefit if non-effusive but no curative.
  – Anti-inflammatory prednisolone (2mg/kg/day) as palliative care.
  – Euthanasia once as sure of diagnosis as possible –> death within a few weeks or months otherwise.
• Now, antiviral treatments available but v expensive (£1000s).
  – Nucleoside analogues –> act as alternative substrate for FCoV RNA synthesis –> RNA chain termination during viral RNA transcription, giving patient’s immune system chance to fight virus. e.g. GS, remdesivir, molnupiravir.

Question 21

UK access to antiviral treatment for FIP.

Answer 21

Access to oral GS and injectable remdesivir as ‘Specials’ preps.
Usually 12-week treatment course.
– Oral GS available as liquid or tabs and cheaper than remdesivir. Dosage given depends on FIP type –> neuro highest, then ocular, then effusive.
– Costs for GS alone £1K-2.5K cost price depending on weight and FIP type.
– Use remdesivir IV (SQ painful) at start, only if cat sick and showing inappetence, but cheaper to use oral GS for full 12 weeks
–> compliance important.

Question 22

Trial treatment for FIP.

Answer 22

Can be given to a cat highly suspect of having FIP.
Helps to conserve funds for treatment and monitoring rather than dx.
Clinical signs e.g. fever, effusion, typically respond w/in 1 week and can be markedly improved.
Takes ~6w for most blood changes to fully resolve. Monitor weight, A:G ratio and AGP.
Sig increased cost if cat gains weight.
Euthanasia is an option and not a failure.
85% response if treated w/ appropriate dosage given for full 12 weeks.

Question 23

Control of FCoV and FIP.

Answer 23

Difficult as hard to understand and is an endemic infection, common and cannot really eradicate.
Advice for multi-cat households.
– minimise stress, reduce overcrowding, reduce other diseases w/ good control etc.
– keep cats in small stable groups.
– Good hygiene, esp. litter trays.
– Don’t rehome kittens too early if poss and minimise their stress after rehoming.
– Ideally stop ALL breeding and quarantine household for 6-12 months.
– Stop using breeding cats that have repeated FIP problems –> esp. males (? passing on genetic susceptibility) and possibly queens too (? infecting kittens).
– Difficult to produce and maintain a FCoV negative household by testing and is unrealistic.