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Winn Feline Foundation Library

2011 Winn Symposium Transcript
June 23, 2011 (published)
Alfred Legendre, DVM, PhD, DACVIM; Niels C. Pedersen, DVM, PhD
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Transcript

To Download each transcript section as a PDF, click the following links:  Part 1 | Part 2 | Part 3 | Part 4

Introduction:

Steve Dale (Master of Ceremonies): 

{Pre-Audio transcript:  That helped us to discover what it was. Of course it was feline leukemia. There was a kind of heart disease, dilated cardiomyopathy. Cats were going blind, cats were dying, no one knew why. Paul Pion, a veterinarian in California, as Californians are known to do, had this crazy idea there was not enough taurine in pet foods. The Winn Feline Foundation supported the research. Funded it. It turns out Dr. Pion was completely correct.
Recently, with diabetes in cats, it turns out with some cats some of the time, increased protein and taking off some weight can put that cat into remission. It was the Winn Feline Foundation that funded that research.

What about FIP? The two pioneers that I will have the honor to introduce are so very responsible for what we know about feline infectious peritonitis. We have been funding Dr. Pedersen for a very long time, from the beginning. In fact, I think Dr. Pedersen has heard me say it, Dr. Legendre has, and it is going to end up in some newspaper or on some blog or maybe some will tweak it…”Is if FIP had happened in the dog world, I think it would have been figured out already.” I’m not wrong on that.}

Sometimes, in fact for years, people said “Well, FIP really doesn’t happen that often.  Dr. Pedersen has pointed out on his sock FIP site that FIP kills 1 in 100 or 1 in 300 of all cats under the ages of 3 to 5, and the incidence is greater when kids are from tarries or from shelters.  Is that enough to do something about it?  Some of you might know about the cat that I had named Ricky.  Do you know who I’m talking about, if any of you heard about this cat?  Well, Ricky played the piano and Ricky was a very social cat.  He would not only play the piano in our house because what cat doesn’t but, we would make appearances and he had recitals at Pet-Co stores or Pet-Smart stores, and Ricky had a bond with me that I don’t think will ever be replicated by a dog or a cat and it turned out he had hypertrophic cardiomyopathy, a kind of heart disease that cats can get, and sometimes these cats often just die, that’s what happened with Ricky, and began the Ricky Fund with the WINN Foundation.

Shortly after that, I heard about a cat named Bria from Susan Gingrich. A little kitten that died of FIP, and she said that same thing that I said about hypertrophic cardiomyopathy.  This has got to stop.  This can’t happen anymore.  We have to make a difference.  And she came to me just after a time when -- and this is what happens, and if some of you are cat breeders, some of you are veterinarians, maybe veterinarian technicians, you know this.  Just cat owners know this.  Here’s what happens.  The cat dies of whatever that cat dies of and then you bring another kitten into that household because the other cat passed away.  There might be kids in the house.  How do you explain to the little kids what happens with FIP?  And here, we had a kitten that we brought in our house.  Our case we don’t have our kids but we have Ringo, what was the cat’s name, a little kitten’s name.  Ringo was just months old and I’ll tell you, we had friends who would come over to our house and said “Steve, you’ve gotten into birds” and I said “Birds?  What do you mean?  But because Ringo, whenever Ringo would walk into a room, Ringo would chirp like a bird, and this was the happiest little kitten that actually never walked into a room but always run into a room.  It does seem that way with FIP, doesn’t it?  It happens to these brave little kittens who come into our lives often because the owners have lost another pet, and I can’t think of anything more awful than that.

I’m here to introduce the speakers.  I’m here to tell you a little about the Winn Foundation, but I’m also here to help us raise money.  We kept the dinner affordable on purpose but there’s a little piece of paper in your envelope and we want you to give and it’s important and I hope you consider that because what you’ve given so far -- to all of you in this room and so many others really has to made a difference, and you’re about to hear how that could make a difference, and at the very least, these little bands are being sold, these green bands, they are just to wear only $5, so I hope you pick up one of those.  As I said, I am the board of directors to the Winn Feline Foundation.  I would like to ask my fellow board members, the colleagues on the board to stand up, if you will.

I am so proud to be on this board because we all have one thing and only one thing, and that is better life for our cats.  So I mentioned this name that I got an e-mail from, and the name Gingrich is kind of, you know, a well-known name in America, so when I got the e-mail, I was like “Hmm, this is interesting.”  Susan Gingrich has done so much to push -- in fact, I don’t believe anyone would say no to her, so if you don’t fill out that little form for me, do it for Susan Gingrich.  Her name is every word on the internet -- no, not on those websites, but she has -- she really has done so much because she and a small army of people including Marlene in Brussels who would send me repeated e-mails, you could applaud her.  Saying “My gosh, I wish I could be there”. Julie Stanton Welsh, who is here, and so many others.  It’s an army of people and I thank you all.

I have some quick acknowledgement to make.  The image right up there comes from Jaime Perry.  When it comes to food, I am happy to say thank you at any time.  Cat Fanciers Association Southern Region arranged the dinner.  We have a legend in this room from the Cat Fanciers Association.  We’ve worked together on legislative projects to do the right thing.  I’m proud to know Joan Miller.  Please stand up.  The Winn Feline Foundation might not be here if it wasn’t for Joan.  Thank you and thank you for everything you do.

When I interview Joan and she goes on about every legislative topic we’re talking about how can anyone be so smart, really.  The Catalyst Council is a non-profit organization; their goal is to elevate the status of [cats. Their Executive Director, Dr. Jane Brunt, is here.  Now, in your packet besides those cards that I hope you fill in the number and give some money, because really, that’s what we need to make a difference are also cards that you ask questions, and at the very end, the members of the board and maybe some of the volunteers that can collect the cards, that’s after Dr. Legendre speaks and after Dr. Pedersen speaks, and they will be here and I will be rattling off some questions for them.  So scribble them out it if you’d like and I’m more than happy to ask the questions that we have time to ask.

This is -- I’m nervous about this.  I’ve done so many things and talked of this in front of so many people but this one is exciting, Dr. Alfred Legendre, professor of internal medicine and oncology, small animal clinical sciences at the College of Veterinary Medicine at the University of Tennessee.  He’s been actively involved in small animal medicine research and teaching for over 30 years with a special interest in infectious diseases, including feline leukemia and FIP.  Dr. Legendre is extensively published and published his first article on FIP in 1975.  He has received lots of awards for his work as a teacher and researcher receiving the Mark L. Morris Lifetime achievement award and the Dr. Robert B Kirk distinguished service award in 2006.  He is also a founding editor the Journal of Veterinarian Internal Medicine published by the American College of Veterinary Internal Medicine, ACVIM.  Please, help me welcome Dr. Legendre.

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Beginning of Part 2 Audio.

Alfred Legendre, DVM, PhD, DACVIM

Dr. Legendre:  Certainly I want to start off by thanking Steve.  Can you hear me back there?

Male Speaker 2:  Yes, go ahead.

Dr. Legendre:  Okay.  I certainly want to thank Steve for this wonderful exaggerated introduction, and also thank the Winn Foundation for the invitation to come in and present to this group the work that is supported by the Winn Foundation.  In addition, I certainly am proud and humble to be on the same stage with Niels Pedersen that I consider the “father of feline infectious peritonitis research” who has been working in that area and has made so many contributions.  We want to go ahead, and let us look at the polyprenyl immunostimulant which is the product that we have been working with as it relates to feline infectious peritonitis and to talk about the polyprenyl itself.  I want to go ahead and start looking at this complex origins of this product and to go ahead, we see on the Russian bear here, we will see Arthur Sas and we will see Tanya Kurtz.  Arthur and Tanya where are you seated?  Back over there.  They are the ones that developed this product.  This comes out originally out of a group of products that we looked at starting way back in the era of the Soviet Union and then in Russia, developing a group of these products, going ahead in conjunction with a variety of different groups.  Which Winn Foundation is certainly good-hearted people who looked at the analysis of the drug, people who have done safety studies. 

Back in 2003, the US Department of Agriculture agreed that they will be the regulators of this product which is up for licensing, so that we’re hopeful in a very short period of time that this product will be licensed and will be available to veterinarians to use as an adjunct to other treatments.  Looking at the Oak Ridge National Laboratory that we are involved, we have two institutes, Veterinarian Institute and the Poliomyelitis Institute in Moscow.  Now, both Arthur and Tanya are from Moscow.  Originally, Tanya has a PhD in molecular biology and Arthur also has a PhD and did a lot of the work for the statistics on this project.  So that is some of the background information that we have on the origin of the polyprenl and here is a picture that Tanya put together.  We were involved with the clinical studies within that one with rhinotrachietis because there is certainly another significant problem in cats as well as the FIP and doing some of the safety studies.  I am sure this is fascinating to everyone.  There is some in the area of organic chemistry that might be of interest as to the structure of the polyprenyl immunostimulant.  One of the things that we addressed with our safety studies is to meet the USDA safety studies.  We are very pleased to get products through the USDA that handles biologics because it’s so much easier to deal with those people than it is to deal with people that at the FDA, but they still have a lot of hurdles to jump. 

First step was to do no harm, and there was safety studies done with a total of 390 cats in 10 states, the rule say that you have to have three different locations and we wound up with 10 different locations, looking at the dosing schedule that we use for the rhinotracheitis treatment which is what the product is going to be licensed under for early rhinotracheitis and we found essentially no adverse effect, there seems to be a safe product, in the 390 cats, there were three of them that really didn’t like the taste of it, one developed diarrhea, and then we have a balance here where two of them, two or three that didn’t like the taste.  We have looked at this product at 10 times the dose that we are dealing with rhinotracheitis without adverse effect and we have gone to 100 times that in some mouse studies without any adverse effect, so it does appear to be quite a safe type product.  Those of you who are into the immunology side, we still think that this falls in to an agent that stimulates toll-like receptors which tends to direct an immune response to a TH1 type of immune response.

This is a cell-mediated immunity which is what you need for viral infections.  So directing, shifting the immune response to a TH1 response through this toll-like receptor mechanism.  Our first study that we looked at was looking at feline rhinotracheitis and I have some studies which suggests that they tend to work well against rhinotracheitis and we see looking at some kittens, 6 - 10 weeks of age and 10 that were in the placebo room, and 10 that were on the treatment group and they were challenged where they were given orally and intranasally, a dose of a rhinotracheitis virus, and then there were those of this dose for a period of 14 days or 15 days and we looked at the before and after evaluated clinical signs and this was one of the kittens that was used in the study.  His name was Felix and he was the virus.  It’s interesting we dug those up because we didn’t have any baby pictures at home.  So what we have in our scheme was we looked at weight loss over the period of time assigning mild; less than 5% of body weight loss or more severe, greater than 5% of body weight loss, one got a 1, one got a 2.  The higher the number, the more clinical signs were seen.  We looked at the nasal discharge on these kittens.  They had moderate light nasal discharge or really thick with a lot of discharge.  We looked at whether the nose obstructed with the nasal discharge or not, whether there was salivation, some of these cats can get ulcers in the mouth, not as bad as we can see occasionally.  We looked at conjunctivitis or inflammation of the eyes whether again; like in the nasal discharge, whether it’s a mild light discharge or heavy discharge, and we looked at moderate hydration and your very typical clinical signs that the kittens with rhinotracheitis will show.

And this is what we saw and as I mentioned, the higher the score, the more clinical signs were seen.  Here again, looking at the daily score and looking at their cumulative scores over a longer period of time and you can see on the red line of the placebo group, you know, all cats showed clinical signs of the ones given the placebo had more severe clinical signs than we had on the other ones that received the polyprenyl and you go ahead and look at the two curves; you can see that the red curve, the control curve, at the height, the curve was much higher as it is typically for a lot of these research projects; we were trying to look at statistical difference at the P = 0.05 level.  We had it at the P.06 level, so now we have got another set of 20 cats that we will be doing to see if we can show that in a larger group of cats, significant differences as an aid to the treatment of feline rhinotracheitis.  If we look at the data in a somewhat different way as to how long the clinical signs persisted in our cats.  And we’re seeing that in this one, our treatment worked here in blue again, in the control group in red, where in the treatment group the signs were pretty much restricted to the first week, so that we have, it showed up about the same time over here, but some of the cats in this group only have about three days and have significant clinical signs, others-four days, six days, seven days, they are pretty much the ones on the experimental group had cleared the infection by the end of seven days, while there seemed to be in placebo group, went on and had problems for much longer, so it does seem to not fully reduce the severity of the rhinotracheitis, it tends to reduce the duration of the rhinotracheitis.  So it’s not a cure-all, but it does help in controlling this very difficult disease process.  Now, looking at feline infectious peritonitis, I don’t have to tell a group like this that it’s a major problem in multiple cat households, the cats coming from shelter environment, certainly appear to be at increased risk for developing feline infectious peritonitis.  Certainly believe that stress is a complicating feature when we’re dealing with the FIP problem and that I am sure Niels is going to be talking further on genetic predisposition, these cats develop FIP.  Now, people say what is the world is going on here, this is a study done by Julie Levy at the University of Florida where she is now involved very much in shelter programs, and this is part of the trap, neuter and release program that was there in feral cats.

And in working with the feral cat population, what was noted when I did the antibody titers for corona virus, they use feral cats.  And a number of feral cats that carry antibodies to corona virus which is the positive agent of FIP is quite low, so that cats in an environment that are spread out, that don’t have that close contact, we know this one is difficult at a dinner meeting, to start talking about fecal-oral transmission of disease.  We know that in these feral cats, they go out there, they have many acres to run on, they bury their stool, and then other cats might have come to contact with it.  The transmission of the corona virus is not a big feature.  But when you’re going in and put cats in a crowded environment, you have the stress of having many cats competing with each other, then that’s certainly sets up the right situation for the development of the persistent corona virus infection and subsequently FIP.

And we see a variety of things that we find the FIP, certainly interference, a depletion, a suppression of the immune response that is necessary for clearing out the corona virus, and clearing this virus and infection from the body and we know that there is a compensatory overproduction of antibodies.  And these are ineffective antibodies so that cats with FIP usually have very high antibody titers, very high body immune modulation that occurs in a situation when you have this persistent antibody production.  We felt that the immune-modulator, like polyprenyl immunostimulant that was originally some of these products were originally tested in the Soviet Union in mice that have viral encephalitis, and they have model systems where 100% of the mice died from the viral encephalitis, and when they added polyprenyl to the mixture they started getting survivors in this uniformly lethal infection where uniformly lethal is what’s been recognized as what’s going on with FIP.  So that we figured that FIP would be a good animal model in relation to try this stuff.

Then we went ahead and some of the things we found early in our trials with the polyprenyl immunostimulant, one we found out that with cats that have the effusive or liquid form of FIP we have no success in those animals, we found that these cats seemed to be so far advanced in the course of their disease, that there was very little hope to turning them around.  Now in looking at the dry form of the FIP we did see some we felt lived longer than expected, and that’s where this is kind of shaky is that how long do you expect them to live.  But after looking at some of our poster children in the treatment with the polyprenyl immunostimulant…

We went ahead, this thing (remote) has a hair trigger, we could have had this presentation in 10 minutes. We reported on three long term survivors, and here we have Gringo which is one of the original group, Gringo had intestinal granulomas, the granulomas were biopsied by the original veterinarian they did ilium staining, and showed that there’s corona virus within the granulomas.  So that was as good as diagnostic choice we could get as hard as determining that the cat truly had FIP and we found Gringo is alive and well, five years now after starting on the polyprenyl immunostimulant.  So that was the encouragement, we submitted to the Winn Foundation to go ahead, and say, is this anecdotal situation just a fluke, or is there a truly any benefit to going ahead and looking at the polyprenyl immunostimulant, we did, we looked at this in the effusive form, soft, no responses, so we focused in only the dry form.

Now, the next step we want to look at is diagnosis, because that was a very key aspect of the last proposal, because with the disease that’s uniformly fatal, if you have a cat that lives a long period of time, what’s the first thing that skeptics are going to say?  Wow, if it lived, it didn’t have FIP, it was supposed to die.  So you really get caught as to have a credible diagnostic criteria for what you call FIP and as you all have found out who have had cats with FIP, making that call.

You really want to put a veterinarian on the spot, just ask him, can you be a 100% sure that this cat has FIP.  Oh hell, I can’t be a 100% sure about anything right now, but that is a very difficult aspect, is that knowing how solid your diagnosis is.  If you get one like this, that has a young kitten from the shelter that has a belly full of the right kind of fluid.  That’s a no-brainer for going ahead and calling that FIP.  Now, when you’re looking at the dry form of FIP what are you looking to make a diagnosis?  One, you’re looking for evidence of these granulomas that this one is a granuloma current in the liver, and if you find within the granuloma, if your immuno stain that shown corona virus in there, that’s probably assuming that there are all the other clinical signs are there, that’s as good as it gets in making a diagnosis.

So once in its dry form, we know that it’s difficult to make a diagnosis, we go ahead and have our criteria which we’ll talk about in a minute.  And then here’s a kidney, and you can see that one of the characteristics of these granulomas is that they do tend to go along vasculature over here, and you can see on the surface of the kidneys the vessels over here and you can see the granulomas of FIP follow along the vessels, you get this picture of the liver, this granuloma and you see the little blood vessel in the center of it.  Now, one of the things that we struggled with in putting the grant together is that being in still preliminary study, we did not have a control group, which is a very, you know, a control group that have been very helpful, but then you go ahead and you don’t have an alternate, it’s one thing when you have two treatments and you’re trying to go ahead and say, which is the better treatment, when you have no alternate treatment you go ahead and say, hey, some of you are going to be in a control group, and your cats are going to die.  That creates a good scientific model to have a placebo group, but the real concern from personal, ethical aspects, those come a lot.  The other thing that we’re looking at in these FIP cases is that we have a situation where a lot of times, is in the long-term making the diagnosis, a lot of times, the disease is quite advanced, by the time that a diagnosis was made, there are very few cats that are diagnosed for FIP, that had not had a course of antibiotic therapy.  Well, maybe this is a hepatic caused infection, so the diagnosis of FIP has usually not come early.

So that’s another complicating factor.  So our criteria for calling it a definitive diagnosis and one of the big ones are the history and physical findings, compatible with FIP.  Such as fever, unresponsive to antibiotics, the lack of response to treatment, a progressive type of a disease process.  Another major factor is an exclusion of other diseases.  We need to have the veterinarians and this was done with veterinarians throughout the country, we did not restrict this to the University of Tennessee.  We had cases that were put on the protocol throughout the country, and when they had working with those veterinarians, as to those things that we needed as part of the workup.  One of the big parts is to go ahead and say, you know, have you considered this, and have you consider that?  A lot of these animals were essentially, all of these animals were tested with feline leukemia virus, and they were tested for feline immunodeficiency virus.  A lot of them were tested for toxoplasmosis, they settled in the right area, they had tests looking for fungal diseases, anything that might mimic FIP.  We wanted to see being that the globulins are increased in most of these cats with FIP.  We put that in as a criteria, we wanted to see highest globulins or antibody levels, low albumins and the albumin globulin ratio was down.  We wanted to see cats that have a moderate to high corona virus antibody titer.  We wanted to see that this was truly when we have lesions that were identifiable, that these were truly granulomatous or highly granulomatous changes that we see.  And that they went ahead and had a biopsy, or an aspirate of these lesions, if highly granulomatous, and if we could get looking at immuno-staining for corona virus.

And the other things that we had depending on what they came in for, we found that looking at PCR of the fluid in the eyes, these are the ones that came in to ophthalmologist, we get ocular fluids that they found the corona virus was in the ocular fluid.  The same thing with finding the corona virus in cerebrospinal fluids, we had some that had MRIs of the brain and I am told by the radiologist that there are some characteristic features of FIP involving the central nervous system, and then going ahead and necropsy findings on those that died, and to date, we have necropsies that results back, on about 8 of the ones that died and that on all of them, there was one with the pathologist was a bit wish-washy as far as calling it.  But they didn’t call it anything else.  This is so typical on pathology reports on cats with FIP and most consistent with feline infectious peritonitis.  They never stated there that your cat has FIP consistent with typical some other terminology, so we felt that our criteria was reasonably good to guarantee that most of these cats had feline infectious peritonitis.  Now, we also had a situation where we included cats that we had in the probable FIP.  And they landed in that area where the people would say, hey I want to participate in this, but I am not going to go ahead and allow a biopsy, to go in and do the exploratory, do a biopsy, a lot of those and of course we have a situation where we did not have a lot of money to work with a diagnostic test.  So that the diagnostic tests were paid for by the owners in this case, so that limited what we could go ahead and do.  But we had a lot of the same criteria for the probable ones, that history and physical findings compatible with, they excluded other diseases, they have the globulins, they have the high corona virus, antibody titers, they have variety of other things compatible with FIP, where they did not have a cytology or histopathology that supported the diagnosis.  Now, looking at the antibody test, as you well know, the antibody tests aren’t an end all and be all in there, but it is an indicator and the diagnosis of FIP is a cumulative diagnosis, you have some of this, and some of that, some of that, some of that, and if you have enough evidence that tips the scale to say yes like the pathologist this is probably FIP and we know this work has been done by Sparks, where he looked a group of 28 cats that had FIP and went ahead and look at a 196 cats that had other diseases that didn’t have FIP.  And we know that the corona virus antibody titers are nonspecific, but we also know that in the ones that had FIP, 96% in his study had some antibodies to corona virus, but there are 86% of those that didn’t have FIP.  So quite common in the population of cats.

When you start looking at high antibody titers, there’s certainly really high values, 25% of the cats with FIP had high values although 6% of the non-FIP cats.  So it’s a bit of a discriminator but it is not the end-all be-all in this situation.  Now, like I said this was a nationwide study, with a few strong cases that we’re able to do with Canada and then we have the permission of the receptive donors send out some polyprenyl to people in variety of other countries.  FIP is certainly not unique to North America type situation, had calls from Australia, Singapore, Korea, just from all over the world.  We went ahead and there’s a variety in here to be used in the diagnostic procedures done by the veterinarians what their usual procedures were and certainly there’s a lot of weight, how strongly a lot of the veterinarians felt if it was FIP and the veterinarians that we work with on this were specialists, they were veterinarians at the feline only clinics, a variety for instance the people that really knew what they were doing.  We initially had put in to do 40 cats and we wanted to put 40 in, you probably have at least 20 that are generally gold or evaluatable or had good follow ups. We ended up taking in a 102 cats in to the study, and stopped about 6 or 8 weeks ago, to go ahead and start analyzing the data and it was the owners that provided funding for the diagnostic tests or the diagnostic procedures.  We have no restrictions on concurrent treatment, all of these cats were on antibiotics, they were on antidiarrheals, they were on steroids, and they were on a variety of other things.

But we did as we could try to decrease the dose of steroids, wean them off of the steroids, because it’s certainly, is that, intuitive to say you don’t want to use an immunosuppressive drug at the same time that you use an immunostimulating drug.  And then we went ahead and all this data came into my office, came into the computer model and I made a subjective evaluation looked at all of these, and I made a subjective evaluation of their data and yes, I agree with their diagnosis of FIP.  So that there was that event as to who’s going to get into, and it was based not only on the criteria, but on the totality of what was presented.  Was it convincing, and we excluded all the effusive FIP cases.  Then we had on the ones that we done, we had monthly physical exams, we evaluated them, to look at you know, weight gain or a loss, whether they’re still febrile, how they were doing, what their appetite had done the previous month, and they were laboratory tests on a monthly basis. 

Okay, let’s look at what was included in this study.  We had 102 cats overall, and we went ahead and 57% qualified, those that were excluded and a lot of these were quite advanced.  I made a special point of not excluding anybody.  I was very careful of skewing the data, and consequently cats or 10% of the number that died before they received the polyprenyl, so that it said that the outcome, I did not exclude those that were hit.  Then we excluded another 13% as far as evaluating ones that died before they’ve been on treatment for a week.  When an immunomodulator to go ahead and turn them around, you know, we’re going to give the equivalent at least a week to work, to have the chance.  Those that were lost to follow up.  We have one person withdrew their cat from the study after starting on the study.  She says, she wanted to give them a holistic approach and went on some herbal medicine and came back in 2 weeks, and wanted to get back on the polyprenyl, she was excluded from the study and we had some that were disqualified for a variety of things, third, we have you know, people that didn’t return the forms so that those are the ones that were disqualified which gives us a total of 58 which to work with. What were these cats, we found that we had pedigreed cats.  We have about 30% which I know is a lot that it would have been higher than that, but we had 30% of pedigreed cats, because of course the breeders who keep up with the literature were much more aware of the initial publication at the public at large.  So this wasn’t hollow, those going on pedigreed, as if somebody it doesn’t fill out that block in the forms, so we have some that somebody who knew who they were.  Now, looking at the forms and FIP that were represented through the study, a lot of them were abdominal, most of them GI with granulomas, small intestine, granulomatous changes in the colon, a lot of them were seen with varying GI signs, big heavy mesenteric lymph nodes, that accounted for the largest group, we had a number of the people in ophthalmology who are aware of what was going on, we have a number of them where ocular lesions were a principal thing, neurologic signs and others were those that like we say in Tennessee they ain’t doing right, and no particular localizing that lesions that we could identify  or aspirate and this is where a lot of those probable FIPs came in.

Now, looking at age, fairly typical distribution we went ahead and looked at the 58 qualifying cats, there were 36% of them that were under 12 months of age, and between 1 and 2 years of age.  We got another 19% over here, so that comes up to 55% if my math is correct.  And then there is some at the older variety of age cats and when we look at the age distribution that we had in our population of cats, with the dry form of FIP, and we look at what was found when we, we have done a survey a few years back looking at the national statistical measure of records from veterinary schools around the country, where they were looking at FIP as a general disease and looking at the percentage of cats in the clinic that had FIP compared to other cats of that age group.  We see that 2 to 6 months of age, the FIP ones are counted in for about in that age group counted for about 12, 13% or less than 10.  In the 6 to 12 months of age, there’s a whole lot of FIP cats than those with other diseases in the clinic.

Again as you can see, equals here somewhere along the 2 or 4 and then as they get older the cats with other diseases, the cats with FIP had lower numbers.  Here’s the data that we have as far as survivors, and you can see that we get into looking at median survival time, median survival time by definition is the number or purported in which 50% of the cats are dead.  So our median survival time was about 50 days and that’s a, you know, and you allow that control group we were talking about, it’s hard to say what that means.  We see that we have a situation where we have cats at various time points that are still alive, so that depending on how long these individuals lived would go ahead and shift that curve to that longest survival time, since this thing was put together last week we have lost two additional cats.  One from disease, and number 29 here was killed by a coyote.

So that we got a situation, and you can see, I think this accounts for one cat that’s still alive here, past the 12-month mark.  So our next step is to go ahead and let the data mature, try to, we’d like to send an email to everybody to keep their cats away from coyotes and more, and see as this curve matures, what our survival time will be.  So in the study, the longest survivor we have is at 289 days, so that the when the study was started around the 10th of March of last year.  And all the cats of course were not accrued all at the same time.  They were accrued over a period of the whole year.  The other thing that we see here is that this designates what type of lesions they had, you can see, 29 had neurologic, and this is 29, here’s the one that was killed by the coyote, when he was sick he was hanging around the house, once he started feeling better, it was hunting again, it was bringing little presents to the owners on a regular basis.  They insisted so that one had been doing well.  We had GI, another neurologic, and ophthalmic, a couple more GIs, neurologic, ophthalmic, GI.  So you can see that there was a wide distribution of types of lesions of FIP, organ systems involved, that we had in here, so it wasn’t restricted to responses in only one.

Now, if we look at the first Kaplan-Meier curve we looked at those that were probable cats, this Kaplan-Meier curve only looks at those that are only the definitive FIPs.  So we see the curve one curve quite mimics the other curve so it doesn’t seem like the probable ones skewed the curve in one way or the other.  We went to look at data on survival times that we have, we know that the survival time on cats, with FIP is quite poor.  This study done by Ritz in Germany and most of these cats were wet form FIP, they’re not going to do it as well.  And you know that they die quite quickly with immediate survival time, half of these cats were dead in 9 days, with the longest survivor they had at 200 days, so they did have, and these were cats treated with the omega interferon, and the one that lived 200 days is now the one that was on the treatment group.  Now there is a study done in Taiwan by Dr. Tsai, and they looked at 46 cats, they went ahead and they looked at mean survival time.  Mean is the average, so if you have some that live a real long time, you will have most of them that died quickly, but then you had some that lived a long time, and it skews your numbers, so that median is a much better method of doing it.  So the time when 50% are still alive, and they found looking at average survival time, mean survival time, that for wet form we got 23 days, and for dry form they got 38 days in the dry form compared to, if you looked at our mean survival time at 81 days.  Now, they had a group they called Mixed where they started off as a dry form, and then they developed some effusion and some of them reabsorbed the effusion, and they found that they didn’t have any median data.  They have a mean survival time of 110 days, which looks very good, but they had two cats who survived 181 days, and over 400 days.

Somebody’s got melfinavir here which is an antiviral drug, that’s one that I thought might be very interesting to use, in combination with polyprenyl.  But they had 5 of the 7 cats; all of these were dead in 19 days.  But they did had some long-term survivors, and whether the melfinavir and human interferon helped or not, but it was not with the data we weren’t able to compare those cats that we have that were still alive, but not okay.  Now if we look at survival by the type of disease that we have, we found that all of those we can see there’s a few of them, that are going out here at a year, and here on the gastrointestinal form, but there’s really not a whole lot of difference between these various curves.  Now the improvement, this seems to be a characteristic here of cats on the polyprenyl; this is an evaluation done by combination of clients and veterinarians where the cats seem to do better.  They felt better, they were eating better, and they will be more playful.  Very, very subjective type things, and of course the ones that lived over a 150 days were some of the ones that were felt to do the best as per the owners.

So let’s look at a couple of these cats that we have, where one of the definitive, this one had, gut lesions, the titers were up in the 1:6400, diarrhea, abdominal masses. This one, the longest one at 374 days.  This little kitten must have been a baby picture since it was seen at 11 months old.  Again, definitive with uveitis and some of the corneal clouding and some of those things.  All these signs resolve and he did quite well for a while, he survived 272 days and it seems like they’ll get better, they’re going along just about the time that you get ready to relax and say, oh, we got this one that’s the corner, some of these were just crash and burn, and it does seem though that when they come to the end, they deteriorate very rapidly.  So that while some of these, I think we do improve quality of life in these animals.  Another one was definitive with fever, weight loss, kind of activity, just improve well being and this one with a 207 day survivor, and this beautiful kitty here, another of the definitive that was out at 289 days and this is Josetta who is a beautiful bengal and this is the one that was killed by the coyote.  And the last we had on it was 198 days.  These are the ones that we have on our hall of fame series, from the earliest ones that we have that we did before we start the Winn study where Grindle, the poster child of five years, and the memory of some of these with others, that were since August of 2009 and this one still alive, this one here, since February of 2010.  This one here was alive when quickly studied, another alive at 18 months, so we aren’t seeing large numbers of cats being long-term survivors.  We are seeing some. So conclusions at this point we believe that the polyprenyl immunostimulant improves the well being and probably survival that cats that had been stable a long time, or that die or euthanized seem to do well for a while and then they fade out quickly in terminal stages.  We want to go ahead in future studies and look at the polyprenyl immunostimulant with either antivirals, looking at some of the small interferon RAs that go ahead, that might stifle the growth, I think you have to control the virus, so that the combination therapy make sense, we need to explore the other uses of the polyprenyl, I want to go ahead and do more of course with rhinotracheitis and see what it will do with cats with ocular Herpes and we want to go ahead and do some more studies on the immunology.  And I want to thank specially Gina Galvin who’s the technician whose part of her salary was funded by the Winn Foundation to try to keep track of all of these.  Tanya Curtis, Arthur Sas, all the veterinarians all that’s in the cast and participated.  Thank you.

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Beginning of Part 3 Audio.

Dr. Niels Pederson

{Pre-Audio transcript, Steve Dale, Master of Ceremonies}: Dr. Niels Pedersen joined the faculty of the School of Veterinary Medicine at UC-Davis in 1972. He spent the first 25 years in clinics, small animal internal medicine, specialty medicine with a special interest in infectious diseases of cats and dogs. Teaching now for 30 years, he has been active in research throughout his career. More that 40 publications in peer-reviewed journals and 40 publications related to FIP. He has had a special interest in feline infectious peritonitis since 1964. Some of us might not be that old. He has received numerous national and international honors. Supported research, particularly with cats. He has written 2 classic textbooks. I have often introduced him as having written the book on feline infectious disease. This guy literally wrote the book on infectious disease in cats. Dr. Pedersen was the first recipient of the CFA’s annual award for contributions to the health of cats, and remains active in consultations. His work with SOCK FIP, he is still working to TKO FIP. Please help me welcome Dr. Niels Pedersen.}

Dr. Niels Pedersen:  Thank you.  No coat but I have a tie.  It's quite an accomplishment.  So okay, I’m going to have to reveal a little of what we’ve done with some of the things that’s been said.  Maybe between Al and myself, we’ve made a little bit clearer because FIP is the most complicated disease that I had personally studied.  Believe me, I’ve studied FIV, I’ve studied FeLV, I’ve studied calicivirus, I've studied herpes virus.  You name it I’ve studied it.  But this is the first disease, the start of the study and it’s the last one that I’m going to study.  I’ve told myself, I will not retire until I have some solution to this disease.  But I have to tell you that every time that I thought that I've had it figured out, it’s thrown me a curve ball.  So I was... what I called a worthy opponent.  Unlike FELV and FIV which were as predictable, as predictable, this disease is totally unpredictable.  Now, I'll probably bring some of that out.  Okay.  So, it's already been mentioned that this is one of the most common infections causes of death in younger cats, 1 to 300 in the nationwide survey of cat vets are responsible.  Mortality is between two and five percent and seen those figures in shelter adopted kittens and purebred kittens as well.  And mortality, I would like to think that there… mortality is virtually 100% with caveat once the clinical signs are appearing, okay.

So, I will tell you there are apparently a lot of cats that do get the infection but never get sick, okay, or at least apparently get sick.  So we will talk about that.  And the other thing that I want you to know is that the death can occur over weeks, months and even years now.  So if I have to say that this disease is like something, it’s most like tuberculosis and that many of these cats get it at a very young age and they can have it in their bodies for all of their life.  And then have it pop out when they’re 10, 12, 14 years of age or some stress or something that occurs at some point in life that it pops out.  So this virus, once it gets in to the tissues in the body, it can hang out there for long periods of time just like tuberculosis.  Many of us have TB or mycobacteria in our lymph nodes tucked away here and there and many of us are immune because we have that little infection and for most of us, that’s a lifetime infection but you don’t realize that.  As we get all get older and our resistance goes down, we have other diseases that the rate of tuberculosis goes back up.  Most of that TB is a part of when we’re younger in life. So, this is something that we need to think about.

I will talk about disease in Burmese and Birman cats where virtually all the FIP is of the dry form and these cats with dry FIP can live for a long time and we have seen a number of cats that are five to seven years of age where they go through that terminal slide that Al was talking about.  And if you look back at those histories, there’s no doubt that they have been sickly for all of their life, okay, and finally the virus gets ahead of them.  I don’t need to tell you that this is a tremendous emotional as well as financial drain on people.  So we have the different groups of cats and we are working with the SF SPCA on the disease in shelter cats… and where did these slides comes from, whoever recognizes these, I didn’t steal it, I borrowed it from Leslie Lyons for a bit, borrowed it from somebody else.  So if you see this and it’s your picture, you come up and put a name on it for me and we will talk begin about Birmans towards the end.  And there are other places that I’d like to mention with too many young cats and these are -- especially kitten rescues.  Kitten rescues have become very popular with the no-kill movement which basically takes cats away from the shelters and puts them out in various places all over the place and many of these kitten rescues are perfectly good.  They do a good job of holding animals until moms are going to be adopted or they can move them back into the, into the shelters for adoption.
But many of these kitten rescues are basically hoarders.  They're excuses for people that are hoarders to legitimize a serious obsessive-compulsive disorder.  So when we look at these areas, these are important areas that we need to consider.  We also recognize that FIP or coronavirus infection does occur in kittens from the field as well.  At least in the Sacramento SPCA, 40% of the kittens that are relinquished at the SPCA are already exposed to coronavirus.  So this is a very common infection out in the wild.

Now, let’s just take some historical perspectives and the first description of this disease was in 1963 by Jean Holzworth, who I consider the greatest feline medicine person that ever lived and probably ever will live and that she described it in Cornell Veterinarian and it… this disease I’d like to say is not, it is a disease that is of relative recent appearance.  It has come out about in the 50s; it appeared in cats for the first time.  So this did not exist a hundred years ago or thousands of years, or 10,000 years ago or 10,000 years ago like FeLV and FIV.  So relatively new infection which would explain in part why the mortality is so high.  It’s because these cats have not a lot of time to evolve a protective mechanism as they've have for FeLV and FIV and a lot of the other infections that we have in cats.

Okay.  So the viral etiology is by Wolf and Griesemer from Ohio State, again, a great home for veterinary pathologist of that era and even today.  And this is just a picture.  So pictures with that first article, again, you see the fluid in the abdomen, you see the peritonitis… this doesn't show it very well.  But I don't want it to be too graphic, I have some very graphic pictures but it’s not really good to show those graphic pictures at meal-time but anyway, this is Jean Holzworth when she was young, how many of you actually knew Jean Holzworth?  And not very many out here.  Jean was the greatest lady that I’ve known.  And here she is in her younger days and she knew more about cat diseases when nobody knew about cat diseases.  This is me, obviously when I first started out, maybe I had comparable time in our two careers and this was the last picture that I had, the pleasure of having with Jean and she died about two years after this picture was taken.  So I decide to mention some of the pioneers in the field and Jean Holzworth is certainly one of the great pioneers.  Okay.  Let’s just talk about where FIP comes from.  There’s been a lot of controversy over the last few years and that controversy has been really quite straightened out.  So I can tell you, the story I’m telling you is the truth, okay?  This is the medical explanation for where FIP comes from based on our knowledge… from our lab and from Utrecht, the Utrecht group, who I consider to be one of the outstanding FIP research groups in the world.

Okay.  So, FIP results from a mutant form of a virus called feline enteric coronavirus.  A lot of people use the term feline coronavirus.  The problem with the term, feline coronavirus, is that it’s not correct because this virus, this FIP virus, the enteric coronavirus were named before that terminology came along.  And the term feline coronavirus is… it’s generic for any coronavirus of cats, okay?  And the virus that causes the enteritis in cats is a coronavirus and the mutant form that causes FIP also is a coronavirus.  So I prefer to use the term feline enteric coronavirus than FIP virus, because then you can understand a little bit more about where these viruses come from and what they do.  Now, feline enteric coronavirus is ubiquitous to all multi-cat environments, indoors and outdoors throughout the world.
There are two strains of the virus, strain one which is called cat-light is 95% or more of the strains in Europe and the United States.  In Asia, dog-like strains are about 20% of the isolates.  So we have two basically, two basic serotypes of enteric coronavirus.

And, this virus is spread by the fecal-oral route.  And I don’t need to tell you that there is no beast known, other than… well, more at to transmit agents by the fecal-oral route than cats, okay?  Especially when you put them in multi-cat environments because you put litter boxes in there and they share those litter boxes.  Litter boxes throw up dust, it gets on your clothes, and it’s all over the place.  And then it drops off in the environment and anything that gets in the environment, you know, goes on the cat’s fur, anything that gets on the cat’s fur goes into the cat’s mouth.  So, this is a normal thing.  So, when you have an environment where you start allowing cats to use litter boxes, then you really up the infection rate.  And now I mention that in their area, in Tennessee, which is more rural than our area, that the infection rate… the feral cats are the one… or the outdoor cats, was relatively low, probably lower than 40% which is the Sacramento area, the urban area.  And that’s again just as Al says, because cats go out there burying their feces.  And the young are usually kept around their mother in the same territory until after they’re weaned.  And so, their contact with other cats… another cat feces is fairly limited.  So, when you bring them into a shelter within a week, that 40% infection rate goes up virtually to 100%.  So within a week’s time in a shelter, that infection rate goes up.  Now, what about catteries?  You guys can… a lot of you can say, "My cattery is free of coronavirus, or free of FIP."  I have never tested a cattery that has more than six cats that raises more than several litters, that goes to shows, that’s swapped kittens back and forth that hasn’t had enteric coronavirus, and I’ve never, never saw… I’ve never seen that cattery.  So, they may insist out there, I don’t doubt that they do, but those of you that feel that you don’t have FIP in your cattery, you may well not have FIP, but you probably have enteric coronavirus.  Especially if you take the young cats from other sources, you go to shows and that type of thing.

Okay, spread by fecal-oral route… primary infection usually occurs around nine weeks of age.  It’s almost imaginable somewhere around nine weeks is when they first start shedding the virus in their stool after the primary infection.  And the primary infection is either non-apparent.  Mostly it’s clinically silent.  You don’t see anything… or you might have a mild diarrhea, sometimes with vomiting for a day, diarrhea for two days, nothing serious, and it’s gone.  Usually you see nothing.  So then after they recover, they shed this virus in their feces for weeks, months, and sometimes years as I’ll show you.  And even after they recover from this infection, most of these guys can be reinfected if they’re exposed again to the… even the same strain that infected them the first time, so they lose their resistance when they lose the infection, many times.  So they could be easily reinfected.

Okay, so what are some of the strange things that go on here?  FIP viruses and FECVs are not too different species of viruses.  This is -- this has come out by a paper by Brown et al a couple of years ago, where they claim that these two virus… these were two different species of viruses that were being passed independently of each other in the environment.  I can tell you that the work of -- our work and the work of Utrecht come out and refuted that fairly strongly.  Now, FIPs always arise from the infected strain of FECV, so if you do a genetic mapping, you sequence the FIP virus that comes from a cattery that has enteric coronavirus in it, that FIP virus will be virtually identical to the enteric virus that’s in that particular cattery.  For another cattery that has another genetic type, those FIPs in that cattery will arise from that genetic type.

So you can literally track by genetics a strain of FIP back to its source, we can do that.  You can track it, if you want to spend enough money, you can find out exactly where it all started just by doing a genetic mapping.  Because the genome of these viruses is just like our genome.  It has all these little differences in it that are… make each of us individuals, okay?  So we can tell the individual strains of viruses very easy.

The other thing is that… excuse me….. the remote is hair-triggered.  Okay, FIPs arise by simple mutations.  Now, from the enteric virus, so during… and I’ll show you this in more detail.  During this primary replication in the gut of this enteric virus, this particular class of viruses has this what we call RNA viruses, in that the way they mutate or that they replicate themselves, they’re very error-prone, so they’re always producing variants, mutants, occurring all the time.  Continuously they’re mutating, all the time mutating.  And you know, we’ve heard about mutation of viruses when we talk about influenza and HIV strains and all sorts of things.  We know that these… that viruses are always mutating.

And so, during this primary infection, there’s… these mutations occur.  Now, if the mutation occurs in a certain gene of the virus, a certain area of the virus that causes the virus to change where it likes to grow.  Now, as I’ll show you, the enteric virus likes to grow in the specific cells of the epithelium in the intestine.  Now, if it mutates in a certain way, that mutant virus then goes into the body and grows not… no longer in the intestinal epithelium, but in what we call macrophages, which, I don’t know if you know what a macrophage is, but it’s a cell that gobbles up things.  It is the most primitive cell in the immune system.  It is the basic cell of the immune system.  It’s a cell that cleans up debris, gobbles up things, and it’s the first thing that initiates the immune response.

So here then, if this mutation occurs, we have a virus that is just a gut virus, that doesn’t do anything.  And if a certain mutation occurs and it goes into the body, infects another cell type altogether, which at the basis of the entire immune system, the macrophage.  And macrophages wander all over the body, so this just spreads the virus all over, and then the immune response against those infected macrophages is what causes the disease that you know of, of FIP.  Now, what are macrophage-loving pathogens?  Tuberculosis, mycobacteria, loves to grow in macrophages.  HIV loves to grow in macrophages.  The deep mycotic infections loved to grow in macrophages.  So there are a lot of infections that love to grow in macrophages.

Okay, so… and once this mutation occurs, as I said, it no longer is able of replicating in the intestine, and it’s found only internally in the diseased tissues, those tissues of that cats that have FIP.  And cats -- and this is important to remember, cats with FIP do not transmit FIP virus to other cats.  So, a cat that has FIP does not infect other cats, it isn’t cat-to-cat transmission.  The only way another cat can get FIP is to start the cycle all over again, start with enteric coronavirus, mutate, have a mutation, and then there’s other factors that kind of come into plays that we’ll or I’ll talk about in a little bit. 

Okay, what is enteric coronavirus?  So this is… if you don’t… you got to understand the basic virus that is that’s out there that’s ubiquitous, that’s everywhere.  And here it is, this is the enemy, and it is called a coronavirus because it has its little projections on the surface which look like crowns, corona means the corona… the crown of the sun, the crown, you know, that corona is a very common term and very appropriate for this particular group of viruses.

Now, this is a just a little cartoon showing you that these are the intestinal villi.  Remember your the intestines are lined by little fingers, right.  Little finger-like projections which is surface area, and right at the tip of your finger is what you call the mature epithelium.  That’s where all the absorption of fluids and the nutrients and so forth, occur, right at the tips, and if you, this virus, this enteric virus has a trophism extremely, just for that cell type.  In fact, no enteric coronavirus that has ever been grown in tissue culture, because you can’t replicate this specific cell, mature cell type in tissue culture.

Okay, here is what we call fluorescent antibody staining.  So the green is where we see virus, and here’s one of those fingers, and the finger goes down here like this and this is the tip of the finger where the mature epithelium is, and you see there’s where the virus is.  It just likes that one little cell right on the tip of the intestinal epithelium.  Okay, and if you look at what happens after the cat is infected, I’ll show you three courses.

So the blue, don’t forget the… just forget the value.  So this means that after they are infected, they start shedding.  So the blue virus, you can see very high levels of virus.  That’s 1015 particles per part of the milligram.  So it’s like unbelievable how many particles come out in the feces of these cats.  It’s like; it’s unbelievable when you talk about billions of viral particles in just a little bit feces.  So here they're shedding, and then this cat stopped shedding after a few weeks, and it recovers, and I noticed that the antibody titer goes up and it goes up to about 1 to 400.  And usually if you have a titer around 1 to 400 and it is accurately done, in the cat, that usually means shedding enteric coronavirus for sure, okay.  And then you see that antibody titer disappears as the infection clears, okay, and so that will go down very low, and then they’ll become… a lot lose their immunity and they could be reinfected again.

So titers do have some value if you have other information to go with it, okay.  So if you were to do, if you were to have a small cattery of let's say six or seven older cats and they all had titers of 1 to 25 and low, you probably don’t have any shedders.  If you have a lot of cats in your cattery and a lot of them are shedders or have titers up around 1 to 400 or 1 to 100, you got it in your cattery even though you will not need to measure the virus, but there are some really neat cheap tests, relatively cheap, that will measure fecal virus shedding.  It’s not as helpful as you think when you figure that in your catteries up to 80% of your cats are shedding at any given time.  So it gives you… it doesn’t give you much helpful information because you could guess already that if you have a large cattery and you have a lot of young cats, a lot of kittens, then you probably have 60-80% or more of your cats shedding.  You can just guess that without spending any money.

Okay, here is another cat that’s shedding persistently for a long period of time.  And then they can shed for many months or even years, you notice that as long as they continue to be infected or shed, that titer will stay up around 1 to 400, 1 to 100, 1 to 400.  So the infection keeps stimulating the immunity.  The infection that goes away, then the antibody drops down.  And here’s one that lost the infection very early, titer went up, titer went down, then it got reinfected.  And then reinfection looks exactly like primary infection.  So in some cases with… some people have asked, "I haven’t had a cat in my household for years.  I have, I have one old cat that’s nine years old, hasn't had any other exposure to cats and then six months ago or eight months ago, I got a young cat because I figured he needed a mate… a partner."  Cats, you should never second guess whether a cat wants a mate or not, you know.  That’s a… I have two cats that are unrelated and they’re the most loving cats that absolutely adore each other, but then my kids have each had two cats and all three of those homes the two cats hate each other.  So it’s all in a draw.

So anyway, never… then in the situation, the older cat will develop FIP.  And so then they’ll say "Where did it come from?  How did they get FIP," …you know.  Well, there are plenty of sources but the one source is probably that younger cat that came in.  It got reinfected again, this type of immune virus occurred and we’re off and running.

Okay, so what is FIP or what is FIPV, FIP virus?  Okay, the FIP virus as I said is greater than 98% related to the same virus that’s found in the feces of those individuals that have died of FIP or dying of FIP and litter mates and other healthy cats in the same environment.  Now not greater than 98% is very related I tell you that.  Genetically that’s a very strong relationship.  And I’ve also mentioned that FIP is a relatively new infection in cats against which they have very little natural resistance.  And you can tell natural resistance.  The wet form of the disease is the cats that are not being part of any immune response at all.  So they are the least immune-responsive of them all.  The cats that have dry FIP are mounting a partial immune response, so that’s why it’s granulomatous and it’s spread out as type course and everything, and we know that in the history of FIP, most of the FIP in the past was wet.  Now we’re seeing progressively more dry FIP in many of our cats and in some breeds like the Burmese and the Birmans, most of the FIP is now dry, indicating that there is an evolution of resistance as time goes on in these cats.  And so at the end, genetics are important and I'll talk about that a little bit more.

Okay, so here we have the cartoon where we have the little viruses or… and then we have just black virus… this are mutant viruses that have the mutation that causes FIP, and these mutant viruses can escape from the bowel because they no longer can infect these cells but now they could gain the ability to infect these macrophages which then take them all over the place.  And now, because they’re macrophage pathogens, the disease that they cause is entirely different than the initial disease.  So here you have two closely related viruses causing entirely different diseases.  Where have you heard that story before, with influenza?  Different strains much more virulent than others, the SARS coronavirus where we had virus that almost went from civet cats into humans and almost made it. Scared the hell out of us, didn’t it?  That killed a few hundred people; it didn't quite adapt itself enough to survive, almost did it.  Maybe the next time it will, so these viruses are doing this to us all the time.

Okay, so this is to tell you that cats have a very short bowel, okay, maybe not that short but anyway… so these cats have had this macrophage trophic virus, they will often go ahead and continue to shed enteric virus from their stool, but this virus here that is in these macrophages is not shed to the outside of the body.  It’s all in the body and the lesions, so the only infection that this cat can cause another cat is another enteric virus infection.  And if you look at the fluorescent antibody staining of the lesion of the cat that has wet FIP in this case, and this is a whole cluster of macrophages, within one of these inflamed lesions and you can see how bright green they are.  They are just chockfull of virus.  Every macrophage is just stuff full of virus.  This is a characteristic of feline infectious peritonitis.

Okay, I'm not going to do many graphic pictures, but I do not understand why veterinarians have so much trouble diagnosing it like me, okay.  I do not understand it because there are just the two forms.  There is the wet form and the dry form and sometimes there is a little intermediate as they can switch from one to another and you can catch them in that transition stage, but people seem to have a hard time making this diagnosis, and like Al said, if you have a young cat from a shelter cattery that has a distended abdomen and has this yellowish, mucinous fluid that contains the right kind of inflammatory cells, high protein… gee, what else is this? What else can we call it?  And the problem that we have is that because the diagnosis of FIP as I said, once they become clinically apparent, they’re going to die, okay, and I tell you right now, they’re going to die.  There is no treatment.  Okay… that I know of, that has been successful to reverse this thing.  Okay, so basically because it’s a fatal disease, people especially veterinarians, and especially owners and especially pathologists; do not want to tell you that this is a fatal disease.  They say, just as Al says.  You get tired of seeing a path report that describes, there's a clinical history just like FIP, lesions that cannot be anything but FIP and then they say, characteristic of FIP, typical FIP.  What does that mean?  You tell me, does it have FIP? Just tell me.

And so, the problem is that in any of these kinds of diseases where there is a 100% mortality and believe me, owners are just as guilty because owners will push that risk, and is there a chance that it is this, or it is that, toxoplasmosis is one million, you know, is it the mycosis, one in a million, you know, all of these things, and so, they are always grasping for stuff and they are pushing it, and the more they push you, the more diagnostic tests that you ask for, and the problem is that hardly any of those diagnostic tests are 100% correct.  And so, even the PCR test maybe only 80%.  Immunohistochemistry might be 70-80% depending on what you do.  The blood work is not 100%.  They are all just little things that help you make the diagnosis, but there is not a single test that’s simple, short of taking a biopsy or taking some fluid, and doing a specific test by a lab that knows what they are doing, which is another problem, okay, to get a decent result back.  And then, you know, then there are still veterinarians refusing to believe that antibody titers are not necessarily diagnostic, so they will continue to do the FIP virus serology on a whole bunch of cats.  One cat will die of FIP in the cattery.  They will test every cat for $30 or $40 a cat, and then they’ll get the results back and then they will say, “Well, I don’t know what they mean.”  So then they’ll call me up.  Well, I didn’t order 50 serologies at $50 a piece, you know, and so they wanted a free consult, you know, as far as I never charge for consults, but they want a consultation as to what that test means, well, no veterinarian should ever ask for a test that they do not know how to interpret it.
If the results come back [Applause] if the results come back and they can’t interpret it, why the hell did they ask for it in the first place?

Okay, so anyway, so much for my bandwagon, and… okay, so now the other form of FIP is the dry form of FIP and in the wet form you can also get it in the chest cavity as well.  The dry form is granulomatous lesions and in 60% of the cats, they are in the abdomen.  The main lesion is the mesenteric lymph nodes, the kidneys, hepatic lymph nodes, liver, spleen, and those types of organs.  And then it can spread from there to the central nervous system and then, eyes are part of the central nervous system, so usually when they have ocular involvement, as this one cat has uveitis in one eye, which is a fairly typical form.  Often will be in the brain and then it can involve the brain and the spinal cord, so you can have the whole spectrum of neurologic signs.  ataxia, incoordination, some kind of seizures, a lot of different kinds of clinical signs associated with this neurologic spread.  Just some typical lesions.

And again, those are called keratic precipitates which are little accumulations of macrophages out there.  Remember, macrophages, again, when the virus likes to grow.  And this is a younger… and this is a young cat with uveitis with keratic precipitates, that's like 99% or 98%.  But again, don’t blame your vets because I have had owners come to me who “The vet said you cat has FIP with 98% certainty," but 98% certainty is still not good enough for those people, so they want me to add the other 2%.  And I'll usually look at them and say, "Hey believe your vet," you know, "in this case, your vet is absolutely right."  Now it does… it isn’t always that case but a lot of times, I'll just say, "Listen, we can’t do much better than this."  And I used the term with my students calling every little laboratory data piece that points to the direction to the certain disease as being another nail in the diagnostic coffin, okay.  This is a human term and it’s the coffin, death, okay, so if you get enough nails on that lid, the person in there is dead, okay?  And they have whatever, you know, you know what that is, and so, we call that, if you give enough indicators, you can get there without being 100%.

Okay, so risk factors for FIP virus.  Okay, the biggest risk factor is you got to be exposed to the enteric coronavirus which is again ubiquitous and largely asymptomatic.  You have to have a mutation in that virus.  Now, how frequent does that virus mutate to cause an FIP virus?  Interestingly, some studies have been done indicating that up to 20% of the cats that are undergoing a primary enteric coronavirus will generate a mutant that can cause FIP.  Now, it doesn’t too much mathematical thing to know that where there is a difference between the 2% to 5 % that die than 20% that get the mutation, right?  So that’s the difference between those that have the ability to mount an immune response to this new macrophage trophic pathogen.  So only about one in five cats that get the mutants actually develop the clinical disease that die.  The rest of them seem to be able to control it relatively well.  So remember I said, the mortality is 100% when they become clinically sick.  Okay, so what are some risk factors of the host… let me go back I maybe missed something.  Okay, no.
Okay, we know that the age of initial exposure plays into this.  Now in the shelter in the cattery environment, this initial infection occurs around 9 to 10 weeks of age.  This is at a time when the immune system is not fully mature.  Remember kittens are not born within a mature immune system.  That starts to really… some of it is mature effort, some types of immune system but remember that their ability starts to grow around four weeks and around sixteen weeks it starts to reach adult levels but it still continues to mature on until a year or even four years of age.  Like for instance, I told you about the little ringworm.  A lot of infection is herpes in a lot of infections of cats.  Some of those cats take several years before they get enough immunity to keep those things, you know damped down.  So if you deal with older cats or older queens, you're going to have a lot less problems than you do when you deal with young queens, you know, for a lot I can name dozens of diseases where that’s the case.

So anyway, so, the fact that this virus in these types of environments, the shelter and the cattery environment occurs at a young age when the immune system is not fully mature, that does I’m sure play a role into it.  Stress, any stress especially in cats.  Remember, cats show stress in two ways.  They defecate, they pee on things they shouldn't, they bite you when you don't expect them to and do things like that.  And then the other stress thing is that their resistance needs to all other infectious agents go up.  So herpes becomes clinical, their calicivirus becomes clinical, much of these diseases start to become clinical, but in a normal kitten, they are under no stress, they would be not clinical or that they are relatively mild.

Okay.  So we have then stresses of all kinds.  And I’m not going to… there are stresses of excess ammonia odors, there are the excesses of diet that are too high in energy causing bacterial overgrowth.  And we can talk about situations that occur in catteries and shelters that have to do with the environment.  Other infections that are occurring at the same time, the herpes and all the other things that are lowering their resistance, so all of these things play into this whole thing.  But also we have the FIP as we do with all the infectious diseases.  Remember now even with HIV, do you realize that the first human known to ever survive has been seen, and that 16% of humans, especially European are resistant to HIV infection naturally.

So the genetics plays a role and many people can get HIV and live a lifetime and then others get it, they’re dead within several months.  So you know, there’s… immunity does play a role, or the genetics does play a role and when we look at one study in a Persian cattery, we could calculate the heritability to be about 50%, which means that 50% of the incidents of disease can be explained by heritable factors.  And the other 50 percent are environmental factors and all these other things.  And how important genetic factors are in a random bred, we don’t know, we know they're important in purebreds but we don’t know in random-breds, they’re probably there, they’re probably at work, but they may not be as much.

Okay.  In conclusion, that is the status of the immune system as the ability to respond rapidly and strongly to this mutation, this mutant virus is key to the outcome.  It determines whether they're going to live or die.  Now, risk factors for husbandry, we mentioned that.  So, we know that increased incidence of virus carriers and magnitude and duration of fecal shedding are increased.  We did a study where we put these cats into shelters and we can tell in the shelter environment that their virus shedding levels went up when they went into the shelter.  Those cats that were shedding at the time went into the cat shelters showed more malnutrition, others stressors we talked about before… again, anything that decreases the ability of the immune system to overcome the mutant virus is going to tip the balance from the host to the virus.  There are other things too that we need to look into.  Early spaying and neutering and all of these other things can tip the balance.  Remember I said it's like TB.  So you get a cat that got this mutant virus and it's fighting it, and it's kind of successful.
You don’t see any clinical signs.  And then you do something to stress that animal.  You tip its immune balance away from resistance to susceptibility.  So you take it and you spay it or you’ll do some other procedure, and so forth and so on and you tip that balance away that they can become clinical.  That also explains why many cattery people will say, “I don’t… I’ve never had a cat with FIP in my cattery."  Yet cats they're given to other people or sold to other people have developed FIP and most of those cats develop that first exposure in the cattery that they originated in.  We can track the virus back to those catteries and those places.  And you think, well, that person is just fibbing you, you know, they’re not telling the truth that they never had FIP in their cattery.  If they let that cat, those cats in that cattery, maybe they would never have gotten FIP, but then they take it, they sell it, they ship it across the country.  They put it into another shelter or another cattery in that…all of that environment, and again, could tip the balance away and Diane Addie did a study.  And I liked Diane a lot because Diane likes these studies with field material.  Admittedly, I would use some field material but I also have to use experimental animals as well, and people ask me how I did that.  Diane will not use experimental animals.  You're limited with what you can prove but it can prove a lot of things.  One of the things that she showed was that that it didn’t really matter the history of the cattery as far as the FIP incidents did not affect the incidents of FIP in cats that were sold or taken from the, those environments.  So she showed that you could have an environment that never had known FIP cases and then will get that at where their kitties went and what happened to them, and you could see that many of them would develop FIP.

Okay.  Approaches to FIP prevention.  Okay, so how are we going to prevent this?  One of the main things that people have talked about is to isolate the pregnant queens prior to parturition, wean kittens as early as possible, remove queens from kittens and raise kittens in isolation.  Okay, this is Diane’s method of doing this.  Now, theoretically this should work good, right?  Or well, because the… I told you that they don’t get infected until they're about nine weeks of age.  Okay.  So isolate the queen whether they’re shedding or not, pull the kittens off at four weeks of age, or as young as you can, take the queen, remove her from the environment, raise the kittens in isolation and voila, they’re free, right?  No.  Because isolation means full quarantine with facilities that are completely quarantined. You're cleaning and suiting up going in and out of the rooms, you know, because this virus is so easily transmitted.  Isolation doesn’t mean queen in bedroom A and another queen in bedroom B, you know.   That’s as hopeless as anything; I'll show you just what we mean by that.

So if you’re going to do this, then, I just have to tell you that you need isolation facilities that are far beyond the scope and isolation quarantine techniques, they are far beyond the scope.  And here’s a study that was done in Switzerland where they, they early weaned this group of cats and then conventionally raised this group of cats.  This is the percentage of the cats that were shedding in their feces and this curve is not statistically different.  These people who thought they were doing something… that they were doing absolutely nothing, okay, and so they’re doing a lot of effort but wasn’t accomplishing anything.  And so if you’re using this technique, at the very least, you need to test your cats after they're 16 weeks of age, test their feces or test for antibodies.  If they're antibody-positive, they’ve been exposed.  If they’ve got virus in their feces, they’ve obviously been exposed.  And then moreover, once you get your cattery free of enteric coronavirus, what are you going to do with it?
You guys show, you show people, you want to trade cats around, you want to buy cats, you want to send your cat some other place, you want to go to shows.  Yeah, you can either… you can get rid of it.  Then you can sit there with your cats for the next 20 years in total isolation, you're getting it to work.  And maybe, if you do it right.  But you’re not going to be breeders and showers, I don’t think anyway.

Okay.  Approaches to FIP.  Effective vaccine.  There’s one vaccine on the market, it’s safe, okay?  That’s all I can say.  It’s not efficacious but it’s safe.  Okay.  And it is unlikely… it is highly unlikely that there ever will be a vaccine for this virus.  Because the truth is, you cannot vaccinate for disease against which the host cannot vaccinate itself in the majority of cases, okay, that’s why there’ll never be an HIV vaccine.  Knock on wood, I hope there will be, but I don’t think so.  And the treatment of HIV is drugs, antiviral drugs, and will probably continue to be that way.  Okay, so I don’t think we’re going to have an effective vaccine but I wish there would be but I doubt it.

Okay.  The bottom line, there is no effective prevention.  We can change our breeding practices.  We do suggest breed away from affected individuals and bloodlines.  If you have toms especially… we made a point that toms that throw kittens, not to use those toms in your breeding and it’s not because toms have... it’s a sex-linked susceptibility factor.  The females have the same resistance and susceptibility factors.  It’s just that if the females have susceptibility factors and you have resistant toms in there, you won’t see much disease, but it’s when you have… you put in a susceptible tom in there.  Remember toms can breed a lot of things to produce a lot of kittens so their genetic effect is much greater especially if they’re passing on a defect.  So it’s just like any genetic disease.  Any simple Mendelian genetic trait.  If you keep breeding away from homozygous or having both alleles of the genetic trait, if your toms are always sound you know, and don’t carry the gene, you’re not going to have a problem for most of those traits unless it’s a dominant trait. 

Okay.  So changes in husbandry practice.  I can tell you the most important thing that you can do other than breed away from individuals is, for God sake, reduce the number of cats that you have in your house.  You know, be smart breeders.  You know, if you have 5 or 6 queens, especially there are older queens, there are proven blood lines, you choose your breedings very close and you’re not willi-nilli breeding everything to everything in the hopes of getting something that is going to win at the show.  That you do it, thinking.  Joan Miller taught me that a long time ago, if you think about your breeding plan, you won’t need near as many cats, you won’t be producing near as many kittens, they’re going to be show winners, you’re going to have a better reputation and so forth.  And it’s the young breeders that end up with too many cats and can’t turn anything down, they can’t get rid of anything and pretty soon, you’re just in big trouble and so be smart about that. 

The bottom line, no effective treatment, no effective antiviral drugs.  Now, I have to tell you that it is doable.  Now, this virus, these coronaviruses have the same replication mechanism that HIV has.  They have an enzyme that converts their RNA to DNA just as HIV.  Remember those are above the reverse transcriptase inhibitors in HIV and some of those… and those drugs, “nuke” drugs are being used on hepatitis A and B cases very effectively, okay, which are also RNA viruses and we’ve actually screened a couple HIV viruses that have antiviral effect against coronaviruses, but the problem is they’re just too toxic.
You know, they’re also too toxic to the cats themselves but there are literally thousands of drugs sitting in depositories that have been developed by many drug companies with all different prototypes of drugs for HIV and those… if you screen those, you would find so many drugs that could work against this disease.  And then from those, you could even fine tune those that will make it a safer and more effective just as what they’ve done to HIV.  What does it cost?  It costs millions of dollars… tens of millions of dollars to develop one of those drugs.  And moreover, you’re not going to cure with these drugs, so you got to do exactly what you do with HIV and that is to treat the disease just as it were diabetes with insulin, all right?  You’ll never going to get rid of HIV, you’re just going to keep the virus levels down. 

So if we did have the antiviral drugs, which I think you can, okay, you can do this.  Now, with non-specific immune modulators.  Dr. Legendre talked about this.  polyprenyl immunostimulant is still under evaluation.  I’d like to comment on… I will comment on interferon… omega and other interferons.  They do not work, okay?  The biggest waste of money that anybody can do is to use these human and cat interferons for the treatment of FIP.  They do not work.  And so basically, that’s what I have to say.  Antiviral drugs, I mentioned the AIDS… the anti-AIDS drugs can work there.

Genetic approach to FIP prevention now in the future.  Okay, avoid bloodlines that… especially, males, not because males carry… just carry, females can too, but that’s the most effective way to handle things that may be done in the future as they determine the genetic factors that increase or decrease the susceptibility and then apply them to breeding.  Okay, in other words, we think that we can identify genetic markers that will tell you which cats are most susceptible to disease and which are most resistant, that’s going to cut the incidence down dramatically if we can do that and we do have… we just had a grant funded to do that.  I’ll talk about that now. 

The reality I’m going to tell you, guys, FIP is not a model for human disease and receives no support from NIH.  NIH supports human-related diseases and animal diseases that are related.  You can make a weak case that this is a lot like SARS or it’s a lot like dengue fever and this… but these are weak cases.  You’re not going to get much money from NIH and so that means that all of your money for this has to come from private sources and it will be costly.  A lot of you think that $5,000 is going to buy you a cure or a cause.  Research is extremely expensive and to run a laboratory, a good research program with good research people is going to cost one lab $300,000 to 400,000 a year.  Is that right, Al?  If you have post docs and all that other stuff, technicians and everything.  So you’re talking about a lot of money to do that and funding for FIP research will come largely from private sources.  These will be individuals who have lost cats, to organizations and foundations.

And then you say, “How can individuals and private organizations make a difference?”  I’m going to tell you about Save Our Cats and Kittens, the original Save Our Cats and Kittens, which had been SOCK it to feline leukemia, which… this organization existed between 1976 and 1992.  This organization took itself out of existence because it was so instrumental in basically eliminating FeLV as infectious disease of importance to pet cats.  Okay, how did we do that?  They raised money.  They raised hundreds of thousands of dollars, this organization, over that period of time.  All went to Davis.  I’m not telling you that you need to send it to Davis, but you need to support people who are doing research.  They decided they want us in.
But out of this pain, those simple diagnostic tests that you all use to diagnose FeLV, that you do it in your home, in your labs and all those little snap tests and all that were developed at UC Davis with this money and it was that test and we were also the first lab to show that you could make FEoV vaccines based on whole viruses.  A lot of vaccines now are based on whole viruses.  Vaccines that we developed are now being used by Intervet and other companies.  But to make the long story short, it wasn’t the vaccines that cured… that took leukemia out of nature.  It was the tests, the rapid ability to test for carriers and to get rid of them, isolate them or get rid of them from the environment and we literally pushed FeLV out.

In 1960s and 70s, early 70s, 30% of the sick cats had FeLV.  Now, we hardly ever see it in our cats.  It’s way out of nature.  We beat it out back into nature where it’s not an important pathogen.  We put it back out of nature.  So again, these things can be highly successful, but they take…they have to be targeted and they require support.  So SOCK FIP is a volunteer group that’s again, working with us.  Some of the members of SOCK FIP are here and have a booth out there.  They’re raising money for research.  Right now, we’re doing the genetic study as well as the study with SF SPCA, with their financial support and with the support of Morris Animal Foundation, Winn Feline Health and this cat consortium.  And I’m not telling you to send your money to Davis.  Send your money to where ever it is being used, the Bria Fund (Winn), Diane Addie funds, whoever, Cornell—Dr. Whittaker’s, all... find a place that’s doing research and give them support.  It’s going to take a little bit of money to do this.  The more researchers that are working on it, the faster this thing is going to get solved.

Okay.  So the Cat… my final thing, the Cat Health Network has been created recently where they’re producing… these are the groups that are working on that and these are working on these high... what we call high-density genetic arrays.  These are 80,000 genetic markers across the whole genome of the cat, which we can use to identify genetic traits within cats.

I just want to end with one last thing.  I’m going to tell you about just the Birman breeders of Denmark.  Maybe it’s my Danish ancestor or my Danish blood.  I don’t know what, but the people of Denmark have been outstanding to me and they introduced 500 samples from their Birman cats in the last year and a half for me for this genetic study.  So I’d like to thank Susanne Wehnert and Anne Sorensen from Denmark and Susan Little and I…

Susan Little and I and Leslie Lyons had the privilege of going to Denmark a few months ago to talk with those people and they’re a great bunch.  So that’s all I have to say.  Thank you.  I’m sorry if I have gone over time.

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Beginning of Questions and Answers Audio.

Question and Answer Session:

Moderator (Steve Dale):  What did we do, we want to increase the use of -- and you'll have to explain what this is and the answers have to be reasonably short gentlemen is for the sake of time; the AGP test to help us diagnose FIP, it is widely we use and valued outside the United States.

Dr. Legendre:  Well, the -- you know, I haven't really used an AGP like...

Moderator:  Explain what this is.

Dr. Legendre:  AGP is basically looking of proteins that identify inflammation, and I think the whole area is going to be very nonspecific, though of course, being an inflammatory disease, cats with FIP could have AGP levels that are up and we've been collecting serum samples from our cats that we'll be looking at just to see as a sidelight.

Dr. Pedersen:  Yeah, and it's just another test measuring chronic immunostimulating, immuno-inflammation, and it's being powered by the Italian Group and the UK Group to a large step.  It's just another test.  It doesn't tell anything more than an elevated white cell count or lymphopenia and A/G ratio that's reversed, an elevated globulin, an increased fibrinogen and blah, blah, blah, you know.  So it's just another one of those tests that test for chronic immune stimulating inflammation, and there are many infections that do that.

Dr. Legendre:  I wouldn't say that it adds an extra 2% to the 98% for diagnosis.

Moderator:  Why do you think that some cats with dry FIP put on EI end up dying from wet FIP?

Dr. Legendre:  I think the transition from dry to wet is just a progression of the disease.  Again, something tilts that balance where it's a deterioration process.

Dr. Pedersen:  Yeah, that's exactly right because if you do follow wet FIP, most of the dry FIP has a brief wet FIP stage that will go unnoticed in most cases unless you're looking at it.  So it often goes initially wet and then as you build immunity it goes dry and if it builds up strong immunity, you see nothing, and so in the end, if you have a dry FIP and your immune system collapses; remember, Al. he accurately said right at the end, it just fall apart, okay.  At that time, the resistance just collapses and then you go wet right at the end and you get some fluid, but that's about it.

Moderator:  Do you plan any studies using melfinavir, human interferon, and PI simultaneously and maybe chicken soup.

Dr. Legendre:  I'd like to see more data because you know, that was just a comment in one of the publications from Taiwan.  I just happen to be done enough with the melfinavir or whatever to say I really – I agree with Niels that interferon, what it's been looked at greatly does not show any benefit.  Some of the interferon would help, I don't know, but I think certain other areas that I think show promise are some of the small interfering RNAs that are interfering with viral growth, but I'd like Niel’s opinion on that.

Moderator:  I know that -- I talked to Dr. Pedersen about this on the radio, in some podcast we’ve done, and having been there myself, I know that I wouldn't have tried the chicken soup.  What do you tell people who call you in desperation, the cat really is diagnosed with effusive FIP or even suspected dry FIP and is willing to try anything?  On the other hand, you hate that people spend their money.  Maybe it's money that would be spent on the next cat medically -- I don't know, what do you think?

Dr. Pedersen:  You tell them the truth, whatever you think and I tell them that if they want chicken soup, they can do chicken soup but I think they should try anything they want, but the truth is I always tell them that there is no effective treatment as far as I know.

Moderator:  Fifty cats in a cattery are tested for coronavirus titer.  All are positive except one adult.  Why is the one negative?

Dr. Pedersen:  The question there is backwards.  It's why the 49 are not -- are positive?  You know, that's a category that has enzootic corona virus, you know, and there is always titers that are first of all, you can have a titer that is falsely negative although it's a lab error.  Out of 50 tests, you have one that's not working, I mean, that's within the range of that and there are cats that have low titers.  They just don't make very much antibody and remember this one; the antibodies are markers of disease.  They're not part of the immune -- the immune response is a little different in this disease, so the antibody is only indicators that they have been exposed, so that doesn't mean that that cat is negative and hasn't been exposed, it isn't immune.  It probably, if that's a true titer, it means it's not shedding at that time.  That's what we would see but the other 49, you know...

Dr. Legendre:  Yeah.  And if we go ahead and compare it to HIV, I mean, there is a nice study that's done in Africa looking at prostitutes that certainly had high exposure to HIV, and a small percentage of those people that were working as a sex worker at this time as the proper terminology never became infected.  So that there's obviously some individuals that for whatever reason, whether they lack the receptors on cells, they just don’t get infected with that particular virus.  Would surprise me to see 1 out of 50 in the cats same way.

Moderator:  What can we do and I love this question and I am going to answer part of it, I’ll let you answer it -- here’s my answer.  Please help us financially so we can when researchers -- but what we do in the Winn Foundation is we meet with submissions.  Actually, our expert scientists do of folks like these two on stage saying “Please grant us money so we can do this”, but we can’t do that and we run out of money.  One of the questions I get -- the most often as well -- why don’t you?  Well, it’s because we only have so many funds, same for the Morris Animal Foundation, same for Cornell Feline Health Center.  I suspect for SOCK FIP the same thing.  Here’s the question:  As cat owners, what can we do to help and research other than money, if our cat is found to have FIP; DNA samples, tissue samples, what can we do?

Dr. Pedersen:  Now you’re going to get me mad.  Because tell you something that maybe you don’t want to hear.  We’ve been pushing for years trying to get breeders -- one thing that you can simply do, just think of how simple this is.  Just take a cue tip and do buccal swab two or three of them, air-dry them, stick it in a paper envelope, not a plastic bag and a little paper envelope, label it -- do this every time you wean a kitten, label the back and stick it in a drawer.  You guys do that for three or four years, you’ll have three generations of pedigree.  So if something comes up and your breed of cat has some disease, you can go back into that thing even if you don’t understand samples, the labs, or you know what, just do that, that’s so simple.  And now, the other thing is I had to go to Denmark to find a breed of registry that would be willing to send me hundreds of samples to do this study.  I had to go to the SF SPCA to work this, you know.  So basically, you guys have resources you can do, but like for instance, if we do this Birman study and come up with a genetic susceptibility marker, we’re going to want to know is that genetic susceptibility marker in Siamese, is it in Maine Coons, is it in Ragdolls, is it in these other breeds as well?  Where’s the samples, you know?  We put out a call -- probably we’ve got 150 samples from total, all the other breeds and 500 from Denmark, so…

Moderator:  You know, I think there used to be -- or maybe it still is and I want you to answer this question.  I mean, when I said if a cat had passed away from FIP…

Moderator:  Because you know, a number of them cases you can only whisper about.  I mean, you think that maybe that’s our problem.  Maybe someone here can tell me how can you forget, but if you keep whispering, we’re not going to be telling the truth and we need to do that, and what Dr. Peterson asked for seems to be perfectly reasonable.  Is someone here from the Cat Fanciers Association?  This should be published in the almanac and promoted in some way because I think what you’re asking for is pretty simple.

Dr. Pedersen:  Yeah, I think it’s pretty simple too.

Moderator:  I may not succeed but I’ll follow on it.  I will try.

Unidentified Male Speaker:  Yeah, and if you have that little envelope and that cat dies of some disease later on; whatever that disease is, you can go back to that envelope and write down on that envelope, died of FIP or died of this or that, died of cancer or lymphoma or whatever.

Moderator:  That would be hugely helpful for a lot of reasons, wouldn’t it?

Dr. Pedersen:  Oh, yeah.

Moderator:  Aside from FIP…

Dr. Pedersen:  Yes, yeah.

Moderator:  How could we get people to do that?

Unidentified Female Speaker:  Explain exactly what you want us to do, like put it in the envelope, what’s that?

Moderator:  She said explain exactly…

Unidentified Female Speaker:  We need to know what you do on your side so we can help you on our side.

Moderator:  So very specific, I’ll give it for the audio here -- very specifically, what do you want them to do?

Dr. Pedersen:  We have it on our website what to do but anyway, the -- all you have to do is take a Q tip, rub it a little bit on the inside the cheek of the mouth, do that for about three of those just set them aside over night and let them dry completely, stick them in a paper envelope, in a porous readable paper envelope, not in a tube, a sealed tube or a plastic Ziploc bag or anything.  Don’t put them in there when they’re wet or they will rot, you know, so they have to be dry completely.  Just sit them there and label the envelope, that’s as simple as it is, that can’t be anymore simpler.

Moderator:  Do they have to be kittens?  Do they have to be breeding cats?

Dr. Pedersen:  Whatever you want, and you know, a DNA is a DNA and you can take it at birth, you could take it at weaning, you could take it at when they -- anytime.  I would first go and take them when they’re all wean, you know, and they’re -- just take a sample.  When they’re old enough that you can handle handle them a little bit better, you know, a nice little swab, a cat’s DNA -- their mouth has a lot of saliva, just full of DNA so they’re very easy -- much easier than dogs and you don’t need cytological brushes or anything like that, just a little Q tip.

Moderator:  Do you want my cat and do you want adult cats also?  I mean, I’ll do it.  I mean, also, is there a form on your website so people can say, you know, “This is from me.  This is the kind of cat I have” and etcetera.

Dr. Pderesen:  Well, I can’t be a repository for millions of cat samples, you know, but what I would be interested is FIP, so I would be interested in breeders that have FIP problem that would give me one of three categories of cats since it’s what we’re asked for in the website.  Category one is cats that have FIP, category two are cats that are close relative; a sibling or a parent of a cat that died of FIP, and group three cats or cats that have no relatives that you know of to the best of your ability who died of FIP.  So you know, I want Persians, I want Burmese and I want all these different breeds, but I’m interested in FIP, okay?

Moderator:  Okay.

Dr. Pedersen:  But I’m telling you that as far as the registry is concerned, I mean, the Cat Fanciers Association; they should start this project as an independent thing and everybody has those samples then a disease can appear five years from now, three years from now, and those samples will be available to be called in.  All you have to do is say “All Siamese breeders.  We want these cats” okay, and you’ll have them in your drawer.

Moderator:  How long is that -- feline coronavirus live outside the body…

Dr. Legendre:  That -- I’m not sure exactly what the survival time is because a lot of times, the coronavirus -- it depends on how clean the area is, the coronavirus will survive for a while.  If it’s in a stool, if it’s in an area where there’s been -- it’s not my understanding -- a very resistant virus like you find with parvovirus, or panleukopenia virus that’s very stable, so just regular cleansers which will clear it out but you’re not going to go ahead if got it deposited in a bunch of stool, it could live for a while.

Moderator:  A couple of weeks?

Dr. Legendre:  Yeah, a couple of weeks in there.

Moderator:  Does scooping more often help?  And also, there was a report of certain kind of litters seem to be resistant at -- do you take any stock in that?

Dr. Legendre: I don’t think -- you know, when you’re scooping, you’re getting the big chunks. Viruses are very tiny. 

Moderator:  Any comment about the litter?

Dr. Pedersen:  Some litter companies are trying to do a research on litters that are antimicrobial, but you know, that’s a big to do because if they’re truly antimicrobial to everything, they’re not going to be that healthy for cats and it’s a difficult thing to do, but the scoop of the litters actually can increase your problems in time because a lot of times, the agents will build up within the litter that is left on.  And as you say, and I mentioned, you scoop out the main ones yeah, but all the rest of the litter is badly contaminated, it gets more contaminated as you go on, so sometimes, scoopable litter actually has a negative impact as far as the infectious agents are concerned.

Moderator:  Has L-lysine been studied, and this is for FIP I assume and not for -- well, like in something L-lysine is used for?

Dr. Legendre:  I don’t think so but I would not expect any miracles there.

Moderator:  Can you talk a bit about vaccination protocols and the potential of over vaccination and if that might be a stress factor for FIP?

Dr. Pedersen:  I got myself into big trouble when they first FeLV vaccine came out years ago because it had a very potent adjuvant and maybe some of you can remember that those kittens will get febrile and sick for several days after they were given that vaccine.  It had a very potent adjuvant and that was changed because of that, but we did see an increase in the FIP and so that’s -- and I did mention that and boy I tell you I almost got sued and everything else, you know, and so -- but as far as most vaccines now, I don’t see any relationship, okay.  I’m totally for vaccination.  Usually, first vaccine dose is around 5 to 6, usually 6 weeks of age, another one 3 or 4 weeks later, and another one around 12 or 16 weeks of age.  Most of the vaccines that are good now -- I don’t think cats need to be vaccinated every year of their life.  That’s a big controversy right now and so -- but I don’t think there’s a relationship to FIP.

Moderator:  Stress is kind of a crazy thing because what stresses one kitten and one household, might not stress another and another household based on the individual kitten, based on maybe when a kitten is raised very, very early on and socialized, so how do you define stress?

Moderator:  It is a tough crowd, isn’t it?

Dr. Legendre:  Before we get into stress, let me throw in a little anecdote here.  Many years ago, we’re working on feline leukemia virus vaccine and we’ve found one manufacturer’s vaccine was that -- well, not significantly better than saline and they -- they were threatening to sue that -- and I talked to Niels “Nah, don’t worry about it.  They’re not going to carry through on that” and they didn’t and it was very reassuring at the time to hear it from him that nah they weren’t going to look at the exposure, so that was very helpful, but looking at the stress issue, you know, we certainly know that there’s a lot of stressors but you really have to ask the cat as to what bothers you.

Dr. Pedersen:  No, but it’s an excellent question because they’re no different than us, and if you look at everyone of you out there, some of you could take all sorts of stress and others you can hardly take any stress.  So what can I say?  And at some cats are the stressees and some are the stressors, just as some people.

Moderator:  Why are you looking at me when you say that?  You said the cats, Dr. Legendre, this is for you, you listed in your study may have been on additional therapeutics in addition to PI. Has there been any correlation with any of these additional therapeutics, kind of asked earlier, you know, maybe I think what some people are getting at, it’s maybe the secret is PI seems to do something.  Wow, we could find something else that does something else.

Unidentified Female Speaker:  No, that wasn’t the question.  Was there any correlation to the length of survival from any of the cats that may have been on any of these therapies or not?

Dr. Legendre:  That has not been analyzed yet.  The most common thing that they were on was steroids so that they -- and that’s been a mainstay of FIP control maintenance for a long time, so I would -- I doubt if that combination really had any advantage, but we have not studied the data yet.  We have not looked at those that had never been on steroids versus the ones, but at a glance without analyzing the data, we don’t see any reason to believe there would be.

Moderator:  Tell me about the Rivalta test.  Is there any diagnostic work to it?  And also explain what that is.

Dr. Pedersen:  The Rivalta test is very simple.  It’s an acetic acid, acetic acid solution.  I mean, you take a drop of the abdominal fluid and you drop it in there and then it will form a precipitate if there’s a lot of inflammatory proteins and protein in it and so it’s a test that’s used to identify a fluid as having an inflammatory nature, okay.  So again, it’s not a specific test, however, I can tell you -- again, if you have a young cat that has a belly full of yellow sticky fluid, yeah, you do a Rivalta test and it will form a precipitate but you already got 98% and what do you want, another -- a half percent?  And so it doesn’t add anything to a normal examination of that fluid, cytology, and protein and that, it’s just…

Dr. Legendre:  Yeah, I agree with that.  I’ve got the Legendre test.  It’s kind of like the Rivalta test.  You take a little fluid in your fingers and you separate it and this strings it out -- yup, that’s probably analogous.

Dr. Pedersen:  And that’s just as good.

Dr. Legendre:  To take advantage is that the Rivalta test is really cheap, the Legendre test is even cheaper.

Moderator:  If you can get it-- I have two more questions here and then I will let you go for the night.  How often do you think cats develop undetected dry FIP and somehow, some way, as both of you had mentioned are able to find out?

Dr. Pedersen:  You know, it’s real, it does happen but you have to be careful.  In my lifetime, I’ve picked up several cats just like Ell, they’ve very vague signs, with enlarged mesenteric lymph nodes and has a localized lesion, and you follow it and it seems to get better and resolve.  Now, I’ve seen a handful of those cases like that in my lifetime, but of that 6 or 7 or half of them are more -- have relapsed after 2, 3, 4 years and have developed clinical FIP later on in life.  Again, supporting that idea; of some of these cats, it just cooks away at sub-clinical level for months even years before it finally pops up and finally…

Moderator:  I think this is an important question.  If a cat is exposed of FIP at another household, can it be brought back into its original household or should be put down.

Dr. Legendre:  I think, you know, being it’s not spread from cat to cat, it only goes ahead and you develop the enteric coronavirus that becomes mutated so that even if that developed FIP at another household and what you might have is that coronavirus in that household and mixed in with that first coronavirus, would that make it more likely to have a mutation?  I have not a clue but I would not think it would -- so that-- but one thing that I’ve been wondering over night was that when I go ahead and throw that out to Niels was that we know in cheetahs that they will go ahead and get seemingly, you know, an outbreak of the FIP syndrome.  I wonder -- have you done any work in that area or looked at those?

Unidentified Male Speaker:  Well, the cheetah situation; cheetahs are totally inbred.  They went through a bottleneck so, genetically every cheetah is virtually the same.  So when there was an outbreak of FIP for the first time in a breeding colony cheetah’s at Oregon, the assumption was that it was going to march through every cheetah and kill every cheetah because every cheetah was a copy of the first cheetah, and it died out just like any coronavirus infection did because they failed to realize that there was an enteric coronavirus that got introduced into that group of cheetahs, and then it mutated and if you have developed FIP and died, then after that, it became enzootic in the cheetahs, the enteric coronavirus, and if the FIP virus had been transmitted from cheetah to cheetah, yes, they would have destroyed all the cheetahs but it didn’t, so that was again another proof that FIP virus mutant is not transmitted.

Moderator:  Well, I feel like the luckiest guy tonight because I got to introduce these two superstars.  Please help me thank them {Standing Ovation}.

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