FIP

Question 1

What is the structure of coronaviruses?

Answer 1

• Enveloped
• • ssRNA

Question 2

How many feline coronaviruses are there?

Answer 2

• 2 serotypes (I and II)
  
  • Based on antigenicity (S protein) of a virus
    
    • resulting from recombination of feline and canine coronavirus genomes including the S gene
  • Serotype I: predominant in the field
  • Either serotype can cause enteric disease or FIP
• 2 biotypes
  
  • Based on clinical presentation
    
    • Feline enteric coronavirus (FECV)
    • Feline Infectious peritonitis virus (FIPV)

Question 3

What are the outcomes of Feline enteric coronavirus?

Answer 3

1. Infection of enterocytes and blunting of the villi
2. Inapparent clinical signs or self-limiting diarrhea
3. Most recover
   
   1. <5% FIP

Question 4

What is Feline Enteric Coronavirus Infection?

Answer 4

• Infects felids (domestic cats, cheetah, mountain lion)
• No clinical signs or self-limiting small bowel diarrhea
• Spreads by fecal-oral route:
  
  • very common fecal pathogen
• High prevalence in multi-cat environments
  
  • ~30% are chronic shedders
  • Immunity is short-lasting - reinfection possible
  • Feline coronavirus can survive for months in a dry environment
  • Viruses are transmitted by direct contact and fomites

Question 5

When was FIP discovered?

Answer 5

• first described in 1963
• Cause-and-effect relationship with feline enteric coronavirus first reported in 1981

Question 6

How common is FIP?

Answer 6

• 1 in 100-200 cats under 2 years old will develop FIP
• Most common in cats of 4 months to 2 years old
• Higher incidences in multi-cat environments
• Sporadic occurrences - outbreaks uncommon

Question 7

Why is FIP important

Answer 7

almost always fatal

Question 8

What are the theories of FIP development? Which one is most widely accepted?

Answer 8

• Two different biotypes circulating theory
• Internal mutation theory:
  
  • widely accepted
  • Ubiquitously present feline enteric coronavirus mutates into FIPV within each cat

Question 9

How does the Internal mutation theory work?

Answer 9

• FECV tropism change through mutations - from enterocytes to monocyte/macrophages
• Impaired T-cell immunity - Humoral (Ab) immune response is NOT protective

Question 10

What virus mutations are implicated in FIP?

Answer 10

• S (spike) protein: viral attachment and entry
  
  • 96% FIPV had 2 mutations at the fusion peptide of S gene
  • Commercial RT-PCR test based on these mutations
    
    • 4% of FIPV does not have mutations & FECV may also have these mutations
• Mutations in accessory genes 3c and 7b

Multiple viral genes, including S gene and others, are likely to be involved in FIP development

Question 11

Is there immunity to FIP?

Answer 11

• Humoral immunity (antibodies) is not protective and may be harmful
  
  • Antibodies to FIPV may facilitate the uptake of the virus into macrophages
  • In experimental FIP studies, cats that have antibodies to FECV progressed faster than naive cats
  • Cats with FIP usually develop strong antibody responses
• Protective immunity to FIPV is largely cell-mediated

Question 12

What are the clinical forms of FIP?

Answer 12

• Wet (effusive) form:
  
  • up to ¾ of cases
  • Chest or abdominal fluid
  • Progress rapidly
  • Average survival time from Dx to euthanasia is about a week
  • Rarely survive more than several weeks
• Dry (non-effusive) form:
  
  • About ¼ cases
  • Survival time is weeks to months, rarely one year
• Dry form may develop effusion at a later stage (dry-to-wet form) Wet form can turn into dry form (wet-to-dry from)

Question 13

What is the Pathogenesis of FIP?

Answer 13

• Immune-mediated
• Virus infects macrophages ⇢ activated macrophages secret inflammatory mediators and triggers inflammatory response ⇢ tissue damage
• Once infected, cytokines, such as Tumor necrosis factor (TNF)-a, secreted by activated macrophages and other immune cells induce T-cell apoptosis leading to lymphopenia ⇢ weaker cellular immunity ⇢ more virus replication
  *

Question 14

What lesions are common with FIP?

Answer 14

• Granulomatous vasculitis
• (pyo)granulomatous lesions (granuloma) in organs
• “Granuloma” - focal area of immune cell aggregates formed in response to chronic inflammation

Question 15

What is Granulomatous vasculitis associated with FIP?

Answer 15

• Accumulation of activated and FIPV-infected circulating monocytes/macrophages in the blood vessel wall or perivenous spaces
• Serosal surfaces (peritoneum or pleura)
  
  • Serositis (peritonitis or pleuritis)
  • Leakage of protein-rich fluid with fibrin
  • Chest or abdominal effusion
• May affect organs such as brain, eyes, lungs, liver, kidneys ⇢ damage their functions

Question 16

Where are the pyogranulomas associated with FIP?

Answer 16

• Parenchymatous abdominal organs
  
  • intestine, liver, kidney, spleen, omentum, pancreas, mesenteric lymph nodes
• Eyes/central nervous system
• Lungs

Question 17

What ocular signs are associated with FIP?

Answer 17

• ~68% bilateral involvement
• Mostly with dry FIP - either alone or with systemic signs
• FIP is most frequent cause of uveitis
• Also:
  
  • keratin precipitates
  • change in coloration of the iris
  • retinal hemorrhage
  • retinal detachment

Question 18

What are the neurological signs associated with FIP?

Answer 18

• Up to 30% of dry FIP develop neurological signs
• More common for dry FIP - either alone or with systemic signs
• Pyogranulomatous inflammatory infiltrates:
  
  • meningitis, ependymitis or periventriculitis
• Abnormal behavior, personality changes
• Seizures, ataxia, paresis, paralysis
• Deficits in cranial nerve function:
  
  • head tilt
  • nystagmus
  • postural reaction deficits
  • anisocoria

Question 19

What are the common clinical manifestations of FIP?

Answer 19

• Clinical signs and time of appearance are dependent on the organs/tissue involved and attributed to the immune status of the cat
• Persistent, undulating fever unresponsive to antibiotics
• Weight loss/failure to grow
• Effusions in abdomen/chest (wet form)
• Anorexia
• Lethargy
• Anemia
• Jaundice
• Ocular lesions
• CNS signs
• Abdominal lymphadenopathy
• Irregular/asymmetrical kidneys
• Ileocolic mass

Question 20

How is FIP diagnosed?

Answer 20

• Can be challenging in dry form - definitive dx usually post-mortem because:
  
  • no clinical signs specific for FIP
  • No lab values specific for FIP
  • Detection of virus or antibody in ‘blood’ does NOT mean FIP
• Dx made through exclusion of other diseases

Question 21

What signalment, clinical and physical features align with a dx of FIP?

Answer 21

• Age: most common for 4 mo - 2yr old cats
• Environment: higher incidences in multi-cat environment
• Clinical findings:
  
  • Fever, lethargy, weight loss, effusions, abdominal palpation/ultrasound (enlarged lymph nodes, intestines or kidney masses), ocular signs, neurological signs, etc

Question 22

What are the common blood abnormalities that align with a dx of FIP?

Answer 22

• ⇡ globulin
• ⇡ Total protein
• Low - low-normal albumin
• ⇡WBC
• lymphopenia
• Non-regenerative anemia
• Hyperbilirubinemia
• Others (eg elevated liver enzymes)

Question 23

How is the Albumin/globulin ratio helpful for a FIP dx?

Answer 23

• helpful for ruling out FIP (when A/G >0.8)
• Cats w/ FIP are highly likely to have A/G ration of < 0.8
• Other diseases can also show A/G of <0.8
  
  • Of cats showing FIP-like symptoms and having A/G < 0.8:
    
    • FIP - 12.5%
    • Other disease - 87.5% (may be treatable)

Question 24

What are the characteristics of the effusion that are associated with a dx of FIP?

Answer 24

• Clear to yellow, viscous fluid
• Protein-rich (High total protein >3.5g/dL)
• A/G ratio < 0.8
• Cytology - modified transudate with low-moderate cellularity < 5,000 cells/uL
  
  • macrophages, neutrophils, and some lymphocytes
• Rivalta test:
  
  • Acetic acid reacts with protein in effusion.
    
    • add one drop of 98% acetic acid (vinegar) to a tube of distilled water, then add a drop of effusion - Positive = drop remains
  • Positive results include FIP, bacterial peritonitis, lymphoma, etc
  • Consider False positives/False negatives!

Question 25

Should dx of FIP be based on RT-PCR on blood or stool?

Answer 25

* No * Blood - can be negative in FIP cats, can be positive in FECV cats * Stool - FIPV typically not shed in stool; FECV will be positive for RT-PCR

Question 26

What dx can be done to confirm FIP?

Answer 26

* IHC or RT-PCR on biopsy or aspirates of tissues * Positive is confirmatory * Lesions can be _missed!_

Question 27

Why are serology test for feline coronavirus Ab unreliable for FIP diagnosis?

Answer 27

* Titers of \> 1 : 1600 may suggest FIP * ~10% of cats with low titers have FIP

Question 28

Do cats with FIP need to be isolated?

Answer 28

* FIPV loses the ability to infect the enterocytes * FIP cats shed no/low titers of virus in stool * The risk of FIPV transmission is very low * Cats in the same household are likely to have already been exposed to feline enteric coronavirus

Question 29

How can FIP be controlled/prevented?

Answer 29

* Routine strict hygiene to reduce FECV contamination

Question 30

What are the challenges in controlling FECV infections

Answer 30

* Chronic shedders - cats may shed viruses for weeks to several months * Reinfection * Feline coronavirus can survive for months is a dry environment * Easily spread by direct ingestion of feces or contaminated litter or fomite (clothes, gloves, carpet, etc)

Question 31

What are the risk factors for FIP?

Answer 31

* Multi-cat environment - continued exposure to FECV * Young age * Stress - surgery, change in environment, other infections * Immune suppression - coinfection with FeLV or FIV * Certain FECV strains have a propensity to mutate into FIPV * Certain breed have higher incidences of dry FIP: * Burmese, Birman, Himalayan, ragdoll, Abyssinian * Bloodline is more important than breed * Multiple gene are likely to play into genetic susceptibility

Question 32

Is there a FIP vaccination?

Answer 32

* NO FECV vaccine * FIP vaccine: * temperature-sensitive modified-live intranasal, FIPV vaccine for kittens of 16 weeks or older * Not a core vaccine * NOT recommended by the AAFP * Limitations: * cats are usually exposed at an early age * Diverse field strains of feline coronavirus