Feline Infectious Peritonitis/Feline Coronavirus (FIP/FCoV)


Date:
Document Type:
Information Sheet
Topics:
Infectious Disease
Species:
Feline

Feline infectious peritonitis (FIP) is a complex and inevitably fatal disease whose mode of transmission and infection is still not entirely understood. While outbreaks or increased rates of infections are rare, shelters should have a plan in place to monitor for elevated rates of disease and to respond appropriately. This information sheet provides a basic overview of this disease and presents some ideas to consider if you face increased FIP rates in your shelter.

Table of Contents: 

Background
Disease course and transmission of FCoV/FIP
Diagnosis of FIP
Vaccination for Feline Coronavirus/FIP
What is an outbreak of FIP?
What are the practical implications for outbreak management?
References

Background

Feline infectious peritonitis (FIP) is one of the most common infectious causes of death in younger cats. It arises as a mutation of feline coronavirus (FCoV) and leads to a fatal systemic disease that progresses over weeks to months. Although infection with FCoV is very common in shelters and other densely housed feline populations, mortality due to feline infectious peritonitis (FIP) is generally low.

Within endemic catteries, about 5-10% of cats with FCoV infection actually develop FIP, whereas within shelters the numbers are typically much lower (less than 1%). The low incidence of disease is fortunate, as vaccination against FCoV is unreliable, diagnosis is rarely straightforward, and so little is known about the disease transmission and development that setting quarantine policies is virtually impossible.

While FCoV is endemic in many multiple cat populations, FIP itself is not thought to be transmitted via direct contact between cats. Despite this, outbreaks involving substantially increased mortality due to FIP do occur in groups of unrelated cats in shelters or catteries.

Disease course and transmission of FCoV/FIP

FCoV is shed extensively in the feces of infected cats and is very readily spread by fomite transmission. Viral shedding may begin within just a few days of infection, and antibody titers will develop within 7-14 days. Although most cats eventually resolve their infection, some cats are chronic shedders and can shed the virus intermittently without clinical signs.

The only method to detect shedders is PCR analysis of feces. A minimum of three samples obtained a month apart are recommended to consider a cat a negative shedder. Most often no clinical signs of FCoV infection are seen; mild diarrhea or respiratory signs may occur but will generally be indistinguishable from other common illnesses in feline populations.

FIP generally results from a mutation of FCoV which occurs anew in each individual cat that develops the disease. This mutated virus is cell-associated and thus is not commonly transmitted directly from one cat to another.  Disease generally develops within a few weeks to 18 months after infection with FCoV, often following a stressor such as rehoming or spay/neuter surgery.

The incidence of disease is bimodal, occurring most commonly in cats younger than 18 months and older than 12 years of age. There appears to be a genetic component that contributes to the risk of developing FIP, thus littermates of kittens that have developed FIP are at increased risk. Unfortunately, there is no way to predict, out of a group of FCoV seropositive cats at risk for FIP, which ones are most likely to develop the disease.

Diagnosis of FIP

A positive diagnosis of FIP can be difficult to make, particularly in the absence of characteristic effusion (fluid in the chest or abdomen). Diagnosis is generally made based on a combination of signalment, clinical signs, blood work, titer results and specific tests.

The most common signs of FIP in young cats include a cyclic fever that is not responsive to antibiotics, lethargy, unexplained weight loss and failure to grow.

Common laboratory abnormalities (see Table 1) include hyperproteinemia (mainly globulin), leukocytosis characterized by neutrophilia, with lymphopenia and anemia. Hyperproteinemia is present in approximately 50% of cats with effusion and 70% of cats without. Serum albumin:globulin ratio can be more useful than globulin measurement alone; ratios greater than 0.8 are uncommon in cats with FIP and can help rule the disease out. Cats with FIP are also often icteric and may have elevated liver enzymes including ALT and ALP.

Table 1 – Laboratory findings and interpretation when considering FIP as a possible diagnosis
Laboratory Findings Interpretation
Hyperproteinemia Common with FIP, but other diseases can also cause it. Not present in all cats with FIP.
Albumin:globulin ratio Ratio greater than 0.8 is possible but uncommon in cats with FIP. A ratio less than 0.8 is not definitive for FIP.
Elevated ALT, ALP, BUN, Creatinine Can be seen with FIP, but not specific. Not seen in every cat with FIP.
Mild non-regenerative anemia Leukocytosis characterized by neutrophilia Lymphopenia Can be seen with FIP, but not specific. Not seen in every cat with FIP.

However, none of these laboratory abnormalities are present in all cats with FIP and there are many other conditions that can lead to any of these findings; therefore, FIP cannot be definitely diagnosed or ruled out based on these bloodwork tests alone.

Definitive diagnosis is only accomplished by visualization of FCoV within macrophages in effusion fluid, or in biopsy or necropsy samples. However, such tests may not always be financially practical in a shelter.

There are however other diagnostic tests that can help aid in the diagnosis of FIP (see Table 2 for summary):

Coronavirus titers: Feline coronavirus titers may be used as an adjunct to diagnosis, however these only indicate whether a cat has been exposed to the near-ubiquitous FCoV. There are no titer tests specific for FIP. If the titer is negative at <1:25, it is likely the cat is truly negative and does not have FIP. It is important to remember that not all laboratories test down to such a low dilution, and a negative titer at higher dilutions (e.g. 1:400) is not meaningful. Very high titers (>1:1,600) are suggestive of FIP, however most cats with FIP do not have titers this high. Rising titers are less informative than they would be for other diseases, because cats with benign FCoV and those with FIP both cycle up and down in titer level. This is particularly likely in a shelter cat, who can be presumed to have suffered a recent onslaught of viral exposure. Occasionally, cats with advanced disease are seronegative due to severe immunosuppression.  

Diagnosis of FIP, or risk for developing FIP, should never be made based on titers alone.

Characteristic effusion: Wet FIP can often be diagnosed with reasonable confidence based on presence of a clear to yellow high protein exudate that contains a low number of nucleated cells (protein levels > 3.5 g/dl, low cellularity of < 5000 cells per microliter). Protein content can be readily assessed in-house using a refractometer. Additionally, the Rivalta Test can be done in-house to further assess suspicious fluid: a test tube is filled with distilled water and one drop of 98% (glacial) acetic acid is added (this can be obtained from chemical supply companies). One drop of effusion is added to this mixture and watched carefully: if the drop dissipates (disappears), the test is negative. If the drop retains its shape, the test is positive. A positive test indicates that the fluid is an exudate, but cytology, cell count, and measurement of the fluid albumin:globulin ratio must still be performed to further characterize the exudate. A fluid albumin:globulin ratio of <0.4 is suggestive of FIP. It is important to remember that other rule outs for an exudate in the abdomen are virtually all serious conditions, and therefore in a shelter that must make euthanasia decisions about some cats, it may be reasonable to euthanize cats based on a strong suspicion of an untreatable condition rather than investing resources on further testing.

Suspicious effusion can be analyzed for antibodies to FCoV. Positive antibody titers had a positive predictive value of 90% in one study, and a negative predictive value of 79%. However, the magnitude of the titer did not correlate with diagnosing FIP. Studies focused on localizing antibodies in CSF are contradictory, and CSF should not be used in order to determine a diagnosis.

Visualization of FCoV Antigen by Immunostaining: This test detects virus-infected macrophages in the tissue via immunocytochemistry or immunohistochemistry, but a biopsy is needed in order to make an evaluation. However, studies have shown that only FIP positive cats will have antigen positive tests. Care must be taken to ensure that the test is performed properly and interpreted correctly. False negatives occur regularly with low infected cellularity or when the virus is complexing with antibody.

PCR: PCR can also be used to detect viral genetic material in tissue or body fluid. However, this test is only capable of detecting coronaviruses in general and not necessarily those that cause FIP. 

Table 2 – Summary of diagnostic tests and interpretation that can help aid in the diagnosis of FIP
Diagnostic Tests Interpretation
Coronavirus Titers In general, a positive titer only indicates exposure to coronavirus, not FIP. If the titer is negative at <1:25, it is likely the cat is truly negative for FIP. Very high titers, >1:1,600, are suggestive of FIP
Rivalta Test A positive test indicates the fluid is an exudate and is highly suggestive of FIP. This test should be performed with cytology to rule out other causes of an exudate.
Effusion albumin:globulin ratio An albumin:globulin ratio <0.4 in the fluid is highly suggestive for FIP.
PCR Positive FCoV PCR indicates exposure to coronavirus, not FIP. Negative PCR does not rule out FIP.
IDEXX RealPCR™ Positive result for FIP in a sick cat is suggestive of FIP.
Visualization of FCoV within macrophages in effusion or tissue samples (by immunohistochemistry) Diagnostic for FIP.

To date, there is no way to screen healthy cats for risk of developing FIP.

Vaccination for FCoV/FIP

There are inherent challenges to creating a truly reliable vaccine for FCoV, given that even natural infection does not convey lasting immunity. There is currently only one vaccine available for feline coronavirus, a modified live intranasal product labeled for use in cats > 16 weeks of age, which is given as a series of two vaccines 3-4 weeks apart.

Results of studies regarding the efficacy of this vaccine have been variable, some showing no efficacy and others showing limited efficacy under certain circumstances. One study showed a significantly decreased risk of FIP in cats that were seronegative for FCoV at the time of vaccination. Although there may be some benefit to giving the vaccine to cats that have never before been exposed to a multi-cat environment (and are therefore relatively likely to be seronegative), most shelter cats will have long since been exposed by the time the recommended booster vaccine can be administered. Based on this information, vaccination is generally not recommended by the American Association of Feline Practitioners (AAFP).

What is an outbreak of FIP?

The frequency of FIP in “coronavirus endemic” catteries, multiple cat homes, and rescue or hoarder homes is reportedly about 5-10%1,4. These are all environments where cats are chronically housed in a high-risk multiple cat environment. In a research cattery following introduction of coronavirus, the rate of FIP was only 0.8% of 1000 exposed cats5, and in a study of cats adopted from an open-intake shelter where cats were only in the environment relatively briefly, the rate of FIP was similarly low at less than 0.6%7. Therefore, rates higher than ~1% in a shelter are cause for concern.

Given that FIP itself is not generally transmitted cat-to-cat and coronavirus is so commonly present in multiple cat populations without causing apparent harm, it is important to understand what accounts for FIP outbreaks.

Although the dynamics of outbreaks are poorly understood, several factors likely contribute:

  • Virulence of FCoVstrain: While FIP itself is not usually transmitted directly between cats, there are strains of coronavirus (“virulent coronaviruses”) that are relatively likely to mutate to FIP.
  • Exposure to high doses and/or high replication in the intestine: Cats exposed to high doses of the virus or that have high levels of viral replication are more likely to develop FIP. Higher rates of replication and consequently higher doses shed into the environment are likely to occur with stress, concurrent illness, and in kittens. One study found that coronavirus mutated readily in FIV infected cats and was shed in a more virulent form at high rates5. Dose effect is also increased by crowding and poor husbandry and sanitation.
  • Exposure to chronic shedder(s): Some cats are more likely than others to become chronic shedders of coronavirus. In one study, 11% of cats from multiple cat households shed coronavirus continuously over a period of up to 5 years8. Many chronic shedders never develop FIP themselves, nor any other clinical signs of infection. If one of these chronic shedders happens to be infected with a relatively virulent strain, this could lead to an increase in FIP cases in exposed cats.
  • Age at exposure: Cats exposed at an early age are more likely to experience infections leading to high levels of replication, shedding, and relatively high risk of FIP. However, FIP can occur at any age; there is evidence of a secondary peak incidence in geriatric cats as a result of sub-optimal immune function. Typically, cats younger than 18 months and older than 12 years are the most at risk for development of FIP.
  • Length of exposure: Although in one study cats were most likely to develop FIP subsequent to a first infection with FCoV10, chronicity of exposure may also play a role. In laboratory studies, a second exposure in previously infected cats led to greater likelihood of FIP (antibody dependent enhancement). Although antibody dependent enhancement has not been documented in the field, the risk of housing cats long term in a rescue home or shelter in which many cats enter carrying various strains of FCoV is unknown. There may be factors common to environments in which many cats are housed long term that predisposes them to increased risk of FIP. In one study, cats that had been in a shelter for > 60 days were over 5 times as likely to be coronavirus positive as cats sheltered less than 5 days11. As noted above, a higher prevalence of FIP has been documented in environments in which multiple cats are housed long term compared to more traditional shelters that house most cats for no more than a few weeks.
  • Genetic risk: Littermates of kittens that develop FIP are at higher risk than unrelated but equivalently-exposed kittens. This is in part because of shared genetic risk, and in part due to exposure to an identical, possibly relatively virulent strain of FIP at a relatively vulnerable time period (very early in life). Although the disease occurs in all breeds, purebred cats are more susceptible; Abyssinians, Australian mist, Bengals, Birmans, Burmese, British shorthairs, Himalayans, ragdolls, rexes, and Scottish folds may be predisposed. Mothers of litters containing one or more FIP kittens may not be at an appreciably increased risk; although they may share some genetic risk factors, they may not have been exposed at a vulnerable time. However, they may be shedding a strain of FCoV that mutated in at least one kitten to FIP.

What are the practical implications for outbreak management?

The difficulties in diagnosing infection and predicting which cats will get ill, the lack of a reliable vaccine, the ease with which FCoV can be spread, and the poorly understood basis of FIP outbreaks combine to create unique challenges for control. Shelters and catteries must decide what to do in the face of an outbreak; whether to quarantine all exposed cats, depopulate, or continue business as usual.

The same questions apply on an individual or household basis when a group of cats have suffered a known exposure to FIP. It is commonly agreed that cats remaining in a household from which a cat developed FIP, or those cats casually exposed to a cat with FIP (for instance, at a veterinary clinic) are not at appreciably increased risk of developing infection themselves. However, the risk of maintaining these cats in a shelter in which they are exposed to an ongoing parade of vulnerable new intakes is unknown. While the risk of introducing cats from such an environment into a home containing naïve cats is likely low, this also poses some problems.

Can all exposed cats be effectively and safely quarantined? There is no way to predict which cats from a shelter having FIP problems are going to get FIP, although littermates of affected kittens are known to be higher risk. There is no realistic way to quarantine cats that have possibly been exposed to a virulent coronavirus: if they are going to get FIP, it could happen any time in the subsequent couple of years. Even if they are not going to get FIP, they may continue to shed coronavirus while under “quarantine” and beyond, which may place other cats (especially kittens) entering the facility at risk. Spread via fomites is so easily accomplished, it is unlikely that true quarantine can be achieved in a shelter facility, even if housed in a separate room from other cats (virus can be easily spread via clothing and shoes).

What is the risk to adopter’s pets? Most likely, if cats from an outbreak environment are adopted out to homes with resident cats, the other cats in the household will not get FIP as a result of this exposure. This is true even if the newly adopted cat happens to be shedding a relatively virulent strain of feline coronavirus or itself eventually succumbs to FIP. This is because the resident pets are likely under less stress than newly admitted shelter cats, and therefore at lower risk of developing FIP secondary to exposure. Development of FIP is even less likely if all cats in the adopter’s household are over 2 years of age, and therefore in a lower risk age group for development of FIP. In general, the risk of FIP is lower in households with less than five cats, as shedding of coronavirus is less likely to be chronically maintained. Although it is very uncommon, occasionally a cat in an adopter’s home can get FIP following exposure to a cat from a shelter with an FIP outbreak. This may be due to transmission of coronavirus from the newly adopted cat and mutation of that virus to FIP in the resident cat. Or, it may be that the resident cat already harbored a coronavirus infection from a prior exposure, and the stress of adding a new pet to the household triggered the manifestations of FIP. Regardless of the reason, this puts the shelter in a difficult and painful position of wondering if a fatal disease was transmitted to an adopter’s pet.

Keeping these difficulties in mind, there are three general strategies for responding to an outbreak of FIP in a cat population:

  • Clean up and carry on as usual: Continue normal operations of intake and adoptions while addressing stress, crowding, sanitation, and concurrent GI infections as effectively as possible. There is never any harm in revisiting these issues in a shelter. It is reasonable to think that if there is a particularly virulent strain of coronavirus in the environment, there would be increased benefit to reducing the dose and reducing cat stress at the time of exposure.

In most cases, FIP outbreaks appear to peter out on their own within a few months to a year even if no special measures are taken. It may be that the virulent strain of coronavirus loses the mutation that conferred its increased propensity to cause disease, as seems to happen with some hypervirulent caliciviruses. Or it may be that the chronic shedders happen to get adopted out, or that the predominant strain of coronavirus circulating in the population gets replaced by a less virulent one. In the meantime, however, the “wait and see” approach has several risks to consider:

  • Poor reputation for the shelter which may compromise future adoptions and community support if many adopted cats end up with FIP
  • Heartbroken adopters if adopted cats develop FIP
  • The small risk that an adopter’s resident cat will develop FIP
  • Make a break between populations: This is an intermediate approach between doing nothing and depopulating. This would involve effectively segregating or removing all current residents and thoroughly cleaning the environment before admitting a new group of cats. However, this is hard to accomplish in many shelters – what are you going to do with all the current residents? Will you adopt them out to new homes from some other facility, in which case you run into the adoption dilemmas described above? Or will you euthanize them, in which case you run into the depopulation dilemmas? Will you hold them in sanctuary forever, or at least for a couple of years until you are reasonably sure they are not going to come down with FIP? A compromise is to at least separate kittens as well as possible from the resident longer term population.

Although it is nearly impossible to prevent all transmission of coronavirus via fomites, it is reasonable to hope to improve matters by at least decreasing the dose new incoming kittens are exposed to by creating very clear separations between populations, having staff handle with separate clothing (or separate staff), and routing visitors through such that they visit the new/clean cats first, then the resident/exposed cats. This has the obvious disadvantage, though, of meaning the exposed cats are even less likely to get adopted. These risks will have to be balanced as best is possible. It is important to diagnose and treat any concurrent infections, as concurrent GI infections can be associated with FIP outbreaks.

  • Depopulate and deep clean. This is not generally a recommended approach. However, if euthanasia is going to be used to control an FIP outbreak, it is important to realize that limited depopulation – such as only kittens or only sickly cats – is unlikely to be effective. Healthy appearing adult cats can chronically shed virus and pose a risk to newly introduced youngsters.

In addition to the loss of life, some risks of depopulation include:

  • Negative impact on community perception of shelter
  • Heartbroken staff and volunteers if cats to which everyone has become attached are euthanized
  • FIP problems can recur even after depopulation efforts

Ultimately, the best defense against FIP are practices that involve good sanitation and biosecurity, humane housing (i.e. compartmentalized housing units), decreased stress, and decreased length of stay (LOS).

References

1. Addie DD, Toth S, Murray GD, et al. Risk of feline infectious peritonitis in cats naturally infected with feline coronavirus. Am J Vet Res 1995;56:429-34.

2. Ettinger, SJ., and EC. Feldman. "Feline Infectious Peritonitis and Feline Coronavirus Infection." Textbook of Veterinary Internal Medicine: Diseases of the Dog and the Cat. St. Louis, MO: Elsevier Saunders, 2010. Print.

3. "Feline Infectious Peritonitis." College of Veterinary Medicine - Cornell University. N.p., n.d. Web. 26 July 2015.

4. Foley JE, Poland A, Carlson J, et al. Risk factors for feline infectious peritonitis among cats in multiple-cat environments with endemic feline enteric coronavirus. Journal of the American Veterinary Medical Association 1997;210:1313-8.

5. Hickman M, Morris Q, Rogers R, et al. Elimination of feline coronavirus infection from a large experimental specific pathogen free cat breeding colony by serologic testing and isolation Feline Practice 1995;23:34-39.

6. Sykes, JE. "Feline Coronavirus Infection." Canine and Feline Infectious Diseases. St. Louis, MO: Elsevier/Saunders, 2014. Print.

7. Spain CV, Scarlett JM, Houpt KA. Long-term risks and benefits of early-age gonadectomy in cats. J Am Vet Med Assoc 2004;224:372-9.

8. Poland AM, Vennema H, Foley JE, et al. Two related strains of feline infectious peritonitis virus isolated from immunocompromised cats infected with a feline enteric coronavirus. J Clin Microbiol 1996;34:3180-4.

9. Addie DD, Jarrett O. Use of a reverse-transcriptase polymerase chain reaction for monitoring the shedding of feline coronavirus by healthy cats. Vet Rec 2001;148:649-53.

10. Addie DD, Schaap IA, Nicolson L, et al. Persistence and transmission of natural type I feline coronavirus infection. J Gen Virol 2003;84:2735-44.

11. Cave TA, Golder MC, Simpson J, et al. Risk factors for feline coronavirus seropositivity in cats relinquished to a UK rescue charity. Journal of Feline Medicine & Surgery 2004;6:53-58.