Feline Infectious Peritonitis
by Helen Cammisa-Parks
[Throughout this article you will see photos of BCR's cats who have had FIP. ]
In keeping with the theme of “Pets and Coronavirus” that appeared in a previous newsletter, this article will focus on feline coronaviruses concentrating on the virus that causes feline infectious peritonitis (FIP). To recap briefly, coronaviruses are a large family of viruses that can cause disease in both humans and animals. There are 2 types of naturally occurring feline coronaviruses; feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV); the latter causing FIP, which currently is an incurable, lethal disease. Of note, no known transmission of FECV from domestic cats to humans has been observed.
Forward
It is highly recommended that you check out the following website: www.sockfip.org. This comprehensive website is chalk full of detailed and valuable information on FIP that is maintained and updated by Dr. Niels Pederson, who is the premier expert on all things FIP. Dr. Pederson has a very interesting background and illustrious career filled with many accolades and awards that you can actually read about on the website (see Autobiography under the Dr. Pederson tab). The striking point regarding Dr. Pederson is that he coauthored his first research paper on FIP that was published in 1964. At that time, not only was there a lack of knowledge about FIP, but there was very little published about cats in general. He has researched many infectious diseases of cats, including feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV); however, FIP continues to be his “first love.” Although officially retired as a distinguished professor emeritus in October 2013 from the University of California at Davis, Dr. Pederson remains an active emeritus faculty and continues his FIP research which “still consumes” him today. He considers FIP to be a “worthy adversary” as it remains one of the most complex and challenging infectious diseases of any species that he is compelled to see prevented and cured.
Another informative website (www.zenbycat.org) is maintained by Peter Cohen, whose cat, Smokey, was diagnosed with FIP and treated successfully by Dr. Pederson’s group at University of California at Davis. There are videos of cat owners who share their personal stories and experience with FIP as well as the use of black-market drugs to treat their beloved felines. Additionally, you can become an “FIP Warrior” by requesting access to this closed Facebook group.
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Background
Feline infectious peritonitis is caused when a common and an otherwise harmless intestinal feline coronavirus (FECV) mutates to FIPV. Approximately 90% of cats who are infected with FECV have either no symptoms or only minor symptoms such as mild diarrhea, recovering with no apparent lingering effects. However, in about 10% of cats, mainly kittens, FECV will undergo specific mutations to FIPV allowing it to escape the cells lining the lower intestine and infect the most basic cell of the immune system, the macrophage. Macrophages are specialized cells involved in recognizing, engulfing, and destroying disease-causing pathogens such as viruses and bacteria. However, some pathogens “trick” the system to avoid being destroyed and thus end up living safely inside the macrophage, cleverly hidden from the immune system. This allows the mutant virus (FIPV) to continue replicating without the body realizing it is a harmful pathogen. The mutant virus (FIPV) is initially confined to local lymphatic tissues associated with the lower intestine. Subsequently, macrophages infected with FIPV can spread the infection to other sites within the abdominal and chest cavities, and to distant organs such as the brain and eyes, causing intense inflammation wherever these infected cells locate.
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| Sissy |
Prevalence and Transmission
Infection with FECV is extremely widespread in cats, especially in environments where many cats are kept together in a small space, such as shelters, catteries, and pet stores. An estimated 25% to 40% of household pet cats have been infected with FECV, with the infection rate increasing to 80% to 100% for cats in multiple-cat households or colonies. Although infection with FECV is very common, the occurrence of FIPV and thus FIP is relatively low. Typically, in shelters, it is expected that the frequency of cats with FIP is less than 1%.
The majority of FECV infections most likely result from ingestion of the virus. Additionally, the virus can be transmitted via inhalation and through saliva, by mutual grooming, sharing the same food bowl, sneezing, and through close contact. Litter box exposure is the key source of infection as cats shed the virus in feces. Cats living in multiple-cat households are at greater risk of FIP. It has been suggested that this disease can move across the placenta from mother to developing kitten; however, the frequency with which this occurs is unknown.
Risk for Developing FIP
Any cat infected with FECV is at risk for developing FIP, with younger cats being at greater risk of developing the disease. Approximately 70% of FIP cases are diagnosed in cats less than 18 months of age, with 50% of cases occurring in cats less than 7 months of age. Additionally, there is evidence of a secondary peak incidence of FIP in geriatric cats due to suboptimal immune function, putting cats older than 12 years of age at greater risk. Although challenging to understand what factors play a role in the development of FIP, the most common route of FECV transmission is thought to occur when infected mothers pass the virus to their kittens, usually when they are five to eight weeks of age. Cats that are housed in high-density facilities, male cats, and purebred cats (including Persian, Abyssinian, Bengal, Birman, Himalayan, Ragdoll, and Rex breeds) appear to be more susceptible to the development of FIP for reasons that remain unclear.
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| Harry |
Signs and Symptoms
Cats that have been initially exposed to FECV usually show no obvious symptoms. Some cats may show mild upper respiratory symptoms such as sneezing, nasal discharge, and watery eyes while others may experience mild gastrointestinal signs such as diarrhea. In most cases, these mild symptoms are self‑limiting. Upon mutation of FECV, cats infected with FIPV usually first develop nonspecific signs of disease such as loss of appetite, unexplained weight loss, depression, and fever. The signs of FIP will vary depending on the extent to which the various organs, including the kidneys, liver, pancreas, central nervous system (CNS) and eyes, are affected.
There are two easily distinguishable forms of FIP referred to as wet (effusive) occurring in approximately two-thirds of infected cats and dry (non-effusive) occurring in about one-third of infected cats. Wet (effusive) FIP tends to have a more rapid onset characterized by a cyclical fever that is resistant to antibiotics, depression, decreased appetite, unexplained weight loss, and the accumulation of a yellow-tinged and moderately sticky fluid in the abdomen, or less commonly in the chest cavity. Cats with abdominal effusions (abnormal accumulation of fluid) usually present with a pot-bellied appearance (abdominal swelling) due to fluid accumulation in the abdomen, while cats with thoracic (chest) effusions often present with labored breathing (exhibited by open-mouthed breathing and/or rapid shallow breathing). In addition, fluid may accumulate around the heart. Of note, cats with mild to moderately severe effusions frequently compensate by decreasing their activity, thus concealing their illness until it is severe. Many of these cats will be noticeably jaundiced due to high levels of bilirubin and/or have strongly yellow-tinged serum and urine. Involvement of the CNS and eyes is relatively uncommon in the wet form of FIP. The majority of all cats with wet FIP will either be euthanized or die within two to 24 weeks. It is rare for a cat with severe abdominal effusions to live beyond 24 weeks.
Cats with dry (non-effusive) FIP tend to be more chronically ill, less likely to have elevated serum bilirubin, and exhibit more vague clinical symptoms of the disease, including lack of appetite, failure to thrive, and weight loss. The dry form of FIP is characterized by less numerous and larger granulomas (tumor-like lesions) in the organs within the abdominal or chest cavities, or in the eyes and brain. These tumor-like lesions affect the functioning of the organ in different ways and lead to secondary infections. Whereas the brain and/or eyes are only involved in 9% of the cases, neurologic and/or ocular disease is seen as the main presenting clinical sign in 70% of cats with dry FIP. Involvement of the eyes and CNS is common and may occur either simultaneously or independently of other signs. When the eyes are affected, there may be bleeding or accumulation of pus in one or both eyes. Other ocular changes, including blindness, can occur. The most common sign of nervous system involvement is poor coordination of muscles with slight paralysis progressing to generalized failure of muscle coordination. Additionally, seizures, tremors, personality changes, and increased sensitivity to touch may be observed.
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| Loki |
Prior to diagnosis, the majority of cats with dry FIP have been subclinically ill for weeks or months and are more likely to be treated symptomatically for weeks or months before they are euthanized or die naturally. Some cats may present with signs of dry FIP but later develop wet FIP, or vice versa. Less than 5% of cats, usually those with milder forms of dry FIP to start, will survive longer than 12 months with the best symptomatic care
Diagnosis
The greatest challenge for veterinarians is the lack of tools for a definitive diagnosis of a disease where time is of the utmost essence. Unfortunately, there is no definitive test to diagnose FIP. Currently, diagnosis of FIP is time-consuming involving invasive procedures that are based on excluding other conditions rather than confirming FIP. Taken together, these factors are particularly detrimental to an already sick cat.
Antibody testing has
proven to be problematic on a number of levels.
While antibody levels (titers) to feline coronavirus can be measured,
this test is not specific in that antibodies to FECV and FIPV cannot be
definitively distinguished from one another. A positive antibody test only
means that a cat has been exposed to a coronavirus, but not necessarily FIPV. Molecular
approaches for detecting the virus have shown promise, but like antibody
testing, are not specific and may miss many viral cases. In addition, some
methods require invasive biopsies of the affected cat and a lengthy time to
prepare the sample for analysis.
Although these tests can be useful, none of them is 100% accurate, and
each suffers from its own limitations that may lead to false-negative or
false-positive results.
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| Carlie |
Development of a new diagnostic test for FIP that is accessible, inexpensive, and fast may be on the horizon with the pioneering work of Dr. Gregg Dean and his research team at Colorado State University’s College of Veterinary Medicine and Biomedical Sciences. According to Dr. Dean: “As we’re moving closer to real, viable treatment possibilities for FIP, having an accurate diagnostic test is going to be an important part of that decision-making process,” he explained. “And an early diagnosis will be important as far as how effective any treatment would be.” The basis of his research focuses on identifying specific biomarkers that are unique to FIP infection as opposed to focusing on the cat’s immune response or looking for the virus itself. If successful, the test for FIP would require only a blood sample from the affected cat.
In light of the fact that there is no definitive diagnostic test for FIP, how does your veterinarian make the diagnosis of FIP? In spite of this limitation, diagnosis is generally made based on a combination of clinical symptoms, specific tests, and blood work. Young cats, particularly between 4 and 16 months of age, that experience a cyclic fever that is not responsive to antibiotics and have lethargy, unexplained weight loss, failure to grow, and high coronavirus titers are often presumptively diagnosed with FIP. This is particularly true if characteristic yellow-tinged fluid with high protein and white blood cell concentrations begins to accumulate within body cavities.
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| Elizabeth |
Treatment
Currently, there is no legally available effective therapy for cats with FIP. Thus, treatment for FIP remains mainly symptomatic (reducing inflammation and suppressing immune reactions). In addition to symptomatic treatments, there is an abundance of information available regarding other therapies, including homeopathic substances, non-specific immunostimulants, and non-specific anti-viral drugs, that have been used with little or no effectiveness in cats with FIP. However, this section will focus on promising targeted anti-viral drug therapies (target specific aspects essential for virus replication) that have been used successfully to treat viral infections in humans such as hepatitis C and human immunodeficiency virus (HIV; the virus that causes AIDS), since these drugs provide the best chance for “curing” this horrific disease of cats.
Dr. Pederson and his research team at the University of California at Davis have conducted field trials in cats with various forms of FIP using 2 different targeted anti-viral compounds, GC376 (viral protease inhibitor) and GS441524 (nucleoside analog). Results from a study utilizing GC376 showed that it was effective in decreasing virus replication and causing remission of disease signs in cats with naturally occurring FIP, with sustained remissions being observed more often in kittens less than 18 weeks of age with wet FIP. Treatment with GC376 appeared to slow the progression of neurologic disease but did not reverse it at the dosage used in this study. On an encouraging note, GC376 was licensed to Anivive Lifesciences in September 2018 in an effort to accelerate the FDA-approval process for treating cats with FIP and eventually bringing GC376 to market.
Recently published results of a field trial with GS-441524 administered to 31 client-owned cats indicate that it is effective and safe in the treatment of FIP. Results from this study taken together with laboratory studies suggest that GS‑441524 may ultimately prove to be an effective treatment option for the wet (effusive) form of FIP. While some cases of the dry form of FIP responded to GS-441524 therapy in these trials, the responses in cases with this form of FIP were not as encouraging as those seen in cases of the wet form. Key information regarding study design and treatment parameters will be critical for future endeavors towards approval and marketing of this or similar compounds against FIP.
Currently, GS‑441524 is currently not approved by the FDA for use in cats. Although FIP is a significant problem in pet cats worldwide, Chinese cat owners were even more desperate for a treatment for FIP than owners in other countries, leading to a Chinese black market for GS-441524. Information on how and where to obtain GS-441524 is easily found on social websites (see FIP Warriors at www.zenbycat.org). These websites feature cat owner groups who have personal experience with FIP and treatment using the black-market version of GS-441524. Although some advice on FIP and how to use these drugs is provided by the Chinese sellers claiming to have veterinary connections, cat owner groups have been of much greater assistance, especially in identifying the most biologically active and economic sources of GS-441524. It is now known that hundreds, if not thousands, of cats around the world are now being successfully treated for FIP using GS‑441524 obtained on the black market, confirming the published research of Dr. Pederson.
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In spite of the extensive experience with GS-441524, a little-known fact among the scientific community is the relationship of GC-441524 to the recently approved drug for COVID-19, remdesivir (Gilead Sciences). Notably, GS‑441524 is the biologically active component of remdesivir, being the first critical step in its production. Prior to the recent approval of remdesivir, Gilead refused to grant the animals rights to GS-441524 fearing Dr. Pederson’s FIP research would interfere with their ability to get remdesivir approved for human use. In part, this refusal led to the Chinese black market for GC-441524. The question remains: “what will happen to the supply of GC-441524 now that remdesivir is approved for the treatment of COVID-19 in humans”? It is logical to assume that this approval creates competition between cats with FIP and humans with COVID-19. Although the approval of remdesivir appears to be the fly in the ointment for cats with FIP, in hindsight, it may turn out to be a blessing in disguise on several fronts. With the US approval of remdesivir, there is hope that Gilead will grant the animal rights for GS-441524. At the very least, the approval for human use makes remdesivir, if not GS-441524, “legally” available through veterinarians. The only caveat is that the safety and efficacy of remdesivir for FIP has not been established yet.
Prevention
The only definitive way to prevent FIP in cats is to prevent FECV infection; a daunting task given its ubiquitous nature. This is particularly true of cats that are housed in high-density settings, such as shelters and catteries. In these settings, the best protection against FIP is practicing good husbandry coupled with humane housing. Keeping cats as healthy as possible, including preventing infection by other viruses such as FeLV and calicivirus, may decrease the likelihood of FIP. Since FECV can be shed in the feces of infected cats, litter boxes should be cleaned and disinfected regularly, and located away from food and water dishes. Separation of newly acquired cats, especially kittens, and cats that are suspected of being infected with FECV from all other cats may prove useful in the management of FIP. Additionally, if your cat died due to FIP, it is recommended to wait at least 2 months before getting another cat to ensure that the virus is no longer present in the environment.
These control measures should be combined with an overall preventive health program for the best possible outcome. However, in households or facilities with a large number of cats, it can be very difficult to eliminate FECV and, as such, the risk for the development of FIP.
Currently, there is only one licensed, approved vaccine available for feline coronavirus (FELOCELL® FIP manufactured by Zoetis), which is an attenuated live virus administered intranasally in two doses given 3 to 4 weeks apart to cats greater than 16 weeks old. The vaccine appears to be safe but the results of its effectiveness in preventing FIP have been variable at best. Taken together with the fact that most shelter cats will have long since been exposed by the time the recommended booster vaccine can be administered, it is not routinely recommended by the American Association of Feline Practitioners Feline Vaccine Advisory Panel. However, cat owners should consult their veterinarian to assist with their decision to vaccinate their cat.
There is hope on the horizon in that a new vaccine candidate may soon be entering the ring in the fight against FIP. In addition to developing a new diagnostic test for FIP (see section on Diagnosis), Dr. Gregg Dean and his team of researchers at Colorado State University will begin the first efficacy trial this fall on an oral vaccine targeting FECV and thus preventing it from mutating to FIPV causing FIP. “The vaccine attempts that have taken place in the past have focused against FIP, but that’s really not the natural situation,” said Dr. Dean. “We know that the enteric coronavirus replicates at an amazing rate, doing millions and millions of experiments. Given this opportunity, there’s a chance that it will mutate into the FIP-causing virus—so this is happening inside the cat more than it’s being transmitted between cats. If we could control that replication, we could hopefully prevent the emergence of the mutant.”
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| Jack |
Additional FIP Resources
Internet searches for “feline enteric coronavirus” or “feline infectious peritonitis” results in an overwhelming amount of information that can be daunting not only to sift through, but can be difficult to understand as some of data is very technical. The following websites serve as good starting points for your search for comprehensive information about FIP that is easily understandable. Several of these websites offer valuable resources to the pet owners whose cat has been diagnosed with FIP.
1) General feline infectious peritonitis resources: www.ccah.sf.ucdavis.edu/cats/resources/general-feline-infectious-peritonitis-resources
2) Save Our Cats and Kittens from Feline Infectious Peritonitis (SOCK FIP): www.sockfip.org
3) Zen by Cat: www.zenbycat.org
4) FIP Warriors 2.0 (private Facebook group that requires a request to join): can access via www.zenbycat.org
5) FELOCELL® FIP vaccine - www.zoetisus.com/products/cats/felocell-fip
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