Finding Biomarkers for the Diagnosis of FIP

Maximus after some treatment, looking hopeful.
Maximus after some treatment, looking hopeful.

Feline Infectious Peritonitis or FIP is notoriously difficult to diagnose. The effusive form causes fluids with a specific color, nature and content to build up in the abdomen or in some circumstances in the chest cavity that can make a diagnosis a little more definitive. Other than that the symptoms are vague, inconsistent and are concurrent with many other conditions and a diagnosis is often made by treating symptoms and watching progress and thereby eliminating any other possibilities. Though it has been known to exist for decades FIP has not been studied as have other diseases; feline illnesses aren’t studied at the rate other species’ illnesses are studied, and funding is often limited.

The Winn Feline Foundation has funded a continuing series of FIP studies over the past several years through The Bria Fund, which focuses on FIP in memory of a cat named Bria who died of the disease. Winn Feline is currently funding a study titled “Host immune response of feline kidney cells to pathogenic and non-pathogenic feline coronavirus strains: Developing biomarkers for FIP” (an abstract of this study can also be found on PubMed).

Feline Infectious Peritonitis Virus (FIPV) and Feline enteric coronavirus (FECV) are similar enough that the goal of this study is to identify biomarkers that can be used to distinguish between the two viruses. The program will study the immune response of various feline cells infected with each virus to better understand the immunity of infected cats. Hopefully the results will enable researchers to develop better diagnostics and improved treatment for FIP. The study is described thus:

“Investigators have analyzed RNA at additional timepoints to the ones proposed in order to insure biomarkers of FIPV infection will not be missed. They also increased the number of samples analysed from 15 to 30 based on their initial results. RNA analysis will hopefully allow identification of genes that are important in FIPV infection and indicate infection with FIPV. Identification of specific genes expressed during infection with FIPV may help to improve diagnostics as well as guide developments of therapeutics. Analysis is ongoing to validate the sequencing data. Publications are planned. (MK)”

What is Feline Infectious Peritonitis, or FIP?

First recognized in the late 1950s with a steady increase in the incidence of the disease from the 1960s to today, FIP kills up to 1 in 100 cats under age 5, and cats coming from more crowded or stressful situations such as shelters or catteries are at five to 10 times greater risk of contracting and developing the disease. It is virtually 100% fatal, meaning no cats have been known to survive for more than a few months beyond diagnosis without symptoms, which can vary widely and mimic other illnesses. Any symptoms can be treated but the treatment is palliative, not curative, and there is currently no known cure for the disease.

FIP begins as feline enteric coronavirus, or FECV, a fairly common intestinal virus among cats and is spread by fecal matter. About 90 percent of cats who come in contact with FECV have only minor symptoms such as mild diarrhea for a few days or no symptoms at all, then recover with no apparent lingering effects.

But in about 10% of infected cats the virus moves from cells in the intestines to a particular white blood cell called a macrophage which exist all over the body. These specialized cells are part of the body’s immune system and have the job of cleaning up dead cells and cellular debris from injuries as well as engulfing disease-causing pathogens and digesting them, sucking it all up like tiny internal vacuum cleaners. However, some pathogens fool the system and avoid being digested and end up living safely inside the macrophage, cleverly hidden from the immune system. This allows the virus to replicate without the body realizing the virus is a pathogen and causing intense inflammation wherever it has decided to settle and replicate. This inflammation is painful but is non-specific and can be generalized all over the cat’s body, which is what leads to the non-specific symptoms which make diagnosis so difficult.

The breakthrough: when FECV becomes FIP

The breakthrough is in determining when and how FECV becomes FIP. “Comparing viral genetics, our lab found exactly what changes when FECV mutates into FIPV. This knowledge will prove pivotal in developing tests, vaccines and treatments to protect cats from this devastating disease,” said Gary Whittaker, virology professor at Cornell’s College of Veterinary Medicine.

But even though FIP cells all start out the same, each rapidly develops its own complications once it begins to replicate. FIP is an RNA-based virus and makes many “mistakes” when it’s replicating—these mistakes are actually mutations so that each incidence of the virus, even within one cat, is different from any other, so tests, vaccines and treatments can’t be determined. “These viruses are so rife with mutations that even samples of the same virus from the same tissue in the same cat rarely match to the letter,” said Whittaker.

Instead of taking piles of samples of the virus to study and look for some similarity or pattern, Whitaker studied a particular area of the FECV virus cell and compared it with the same area on the FIP virus cell and found a mutation. Whittaker was able to consistently locate this mutation across hundreds of feline coronavirus samples he had collected from pet owners, veterinarians, and Cornell’s pathology vault, the school reported.

A few more details about FIP

There are two forms of FIP, referred to as granulomatous, or dry, FIP and effusive, or wet, FIP; the first has no obvious symptoms, the second form causes fluids to build up in the abdominal or pleural cavity. This fluid can be drained but will usually return, and the fluid itself puts a strain on the body’s function and on the immune system. The dry form has little to no fluids developing in the body, but lesions develop on the internal organs and these lesions variously affect the organ’s function and lead to secondary infection.

In both cases the immune system is greatly compromised, secondary infections are common, and neurological symptoms such as changes in eye function or vision loss, or difficulty balancing or walking which develops to functional paralysis. On the outside, however, the cat often looks completely normal.

Oddly enough, FIP itself is not truly contagious. FECV is shed in the feces and can be passed on to other cats, but it is not FIP until the mutation which happens as it replicates inside macrophages, but these cannot be shed.

Why we care deeply about FIP

black kitten with heart.
Lucy with her amber heart.

We care about all health issues involving cats, but FIP is very personal. I’ve often mentioned Lucy, the little black kitten born to Mimi the year before the Fantastic Four were born, and that she developed and died of the effusive form of FIP at 15 months. In part, the propensity to develop the disease is thought to be genetic, and I’ve got five members of Lucy’s family here, and I am in touch with a number of others and their adoptive humans. As research on the disease progresses we want to know, and we certainly don’t want anyone else to lose a kitten in the way we lost Lucy.

FIP can cause other symptoms as well, and while the effusive form which Lucy had was clearly enough FIP, the granulomatous form does not necessarily show any symptoms that could not also be other common conditions from pancreatitis to early cancer. Because Mimi was Lucy’s mother, and because I saw other odd symptoms in her in the past year and even earlier, FIP is actually in the running for what is causing her current condition. Cats with the dry form have been known to live a fairly normal life until their senior years when the disease can take a greater hold on their body and immune system.

Having a good stretch and coming to say hello.
Having a good stretch and coming to say hello.

. . . . . . .

Resources:

Feline Infectious Peritonitis/Feline Enteric Coronavirus (FIP/FECV)

Discovery offers hope against deadly cat virus


. . . . . . .

Maximus the day he was rescued.
Maximus the day he was rescued.

NOTE: The handsome sealpoint cat at the top and here was Maximus, a cat rescued by Pittsburgh CAT volunteer Tarra Provident and who was diagnosed with FIP. Tarra happened to see this cat posted as “found in a box by the side of the road” on a craigslist local rehoming page for pets, saying he was obviously ill or injured and they couldn’t afford his care. He was weak and thin and dehydrated and showing some neurological symptoms that could have been related to that neglect, and appeared to be about four months old. When examined at the clinic he turned out to be an unneutered male at least a year old though he only weighed 2.5 pounds. He was also found to be anemic and his pupils were of uneven size, which you can see in the photo at the top, and Dr. Morrow suspected FIP right away.

On investigating the people it became clear he was not found along the road in a box but had been their cat–he appeared in photos on their Facebook page dating to last year along with other animals they bred for sale.

Nonetheless he did begin to respond to fluids and foods and love—not surprisingly he was a very loving kitty even with what he’d been through and what pain he was suffering then—and had a good week, but began to deteriorate. After two weeks it was clear he was suffering even more and he was put to sleep. How long he suffered with the effects of FIP, if he’d ever seen a vet, what would have happened to him if he hadn’t been rescued off craigslist it’s hard to tell, but after suffering FIP and neglect at the same time at least he knew love and care in those last two weeks. We won’t forget you, Maximus, or other cats like you.

Maximus on his last day.
Maximus on his last day.

Read more articles about Health and Safety and Veterinary Medicine.

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From health and welfare to rescue and adoption stories, advocacy and art, The Creative Cat offers both visual and verbal education and entertainment about cats for people who love cats. From catchy and creative headlines to factual articles and fictional stories, The Creative Cat provides constant entertainment and important information to people who love cats, pets and animals of all species.

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