Wednesday, 26 March 2014

Murphy - misdiagnosis of wet FIP

Mischievous Murphy from Germany is a kitten successfully treated for bacterial peritonitis which was initially mis-diagnosed as FIP in April 2013 when he was 8 months old. Fortunately Jennifer did not give up. She found a second opinion from another vet, who although she could not rule out FIP even though his abdominal fluid tested negative for coronavirus, committed to save him and went for treating the treatable in the face of uncertainty. Murphy was given Suanatem (Metronidazole and Spiramycin) and recovered quickly.

This continues the series on misdiagnosis. Please make sure you check out Dr Addies's diagnostic algorithm's for FIP on treatment page before losing hope. And donate to FIP research which is working towards a fast and reliable diagnostic tool. In australia this is University of Sydney with Jaqui Norris.

Thursday, 13 March 2014

Mutant Ninja FIP

"Evolutionary plasticity can be purchased only at the ruthlessly dear price of continuously sacrificing some individuals to death from unfavourable mutations."

~Theodosius Dobzhansky Genetics and the Origin of Species (1937)

Life does not stand still. Evidence of the mutation of Feline crossed Canine coronavirus to produce a virulent form that creates directly cat-cat transmissible FIP disease. Marleen from Facebook FIP fighters group posted this today -
"One of our members contacted Dr. Niels Pedersen from the UC Davic SOCK FIP team and he kindly sent her this lengthy reply (see below). She got his permision to share this with the FIP community.
Q: In a recent article by Wang et al ( an outbreak of FIP among cats in a Taiwanese shelter was described. This has caused some anxiety among cat owners concerning the potential of cat-to-cat transmission of FIPV. What are your views on this? 
A: I reviewed this paper and believe that this was a case that started with cat-to-cat transmission. However, the virus in this outbreak is what we call type II FIPV, which is a hybrid that occurs between feline and canine coronavirus. The primary strain of coronavirus in most cats is serotype I. Serotype II FIPV are more virulent than type I viruses and there is an old report of possible cat-to-cat transmission with another FIP virus of this serotype. However, this is a very rare occurrence and should not be taken as a universal finding. Cat-to-cat transmission of FIPV is extremely uncommon, even with serotype II virus, and when it occurs the outbreaks are self-limiting because the virus rapidly mutates to a form that does not go cat-to-cat. It is likely that the virus in this outbreak came from a cat or cats that were housed with dogs in another shelter and had not yet had time to fully adapt to cats. 
At this point, we need to define the difference between epizootic (epidemic=human) and enzootic (endemic=human) disease. An epizootic occurs when a new pathogen such as a virus enters a group of susceptible animals for the first time. There is a very rapid spread with a high morbidity (prevalence of diseased individuals) and often a high mortality (death from that disesae). An example would be the appearance of parvo virus enteritis in dogs in the 1970s, an epizootic disease that is now enzootic. Enzootic disease occurs when a pathogen lurks continuously in the environment and only targets individuals that become susceptible. For instance, feline enteric coronavirus is shed by a majority of older cats in a cattery but it is the kittens that take the brunt of disease. Enzootic disease is sporadic in nature and the morbidity and mortality waxes and wanes depending on the presence or absence of disease cofactors. People often mistake epizootic for enzootic disease when several cases occur close together. Epizootics usually get far more attention than enzootics, because they hit like a hammer. Enzootic disease is frequently tolerated, as is the case with feline upper respiratory and intestinal infections and even with FIP. However, the tap-tap-tap of enzootic disease is in the long run far more damaging and causes far more deaths than epizootic disease. 

Q: How can an epizootic of FIP, such as occurred in this Taiwan shelter, be differentiated from the enzootic type disease that causes almost all FIP deaths? Or another way to ask the question in the case of FIP is how can you differentiate cat-to-cat transmission of an FIP virus from the normal pattern of infection, which involves cat-to-cat transmission of the parent feline enteric coronavirus followed by internal mutation of the disease causing FIP virus?
A:  The epizootic of FIP that occurred in Taiwan was easy to characterize, because it could be traced to the introduction of a specific hybrid cat/dog virus that came in with a cat from another environment. This virus then rapidly spread to susceptible cats by contact. The virus that caused the epizootic was also genetically unique from normal enteric coronaviruses that were enzootic to the shelter, confirming that it was indeed a new introduction. As would be expected from an epizootic, the introduced virus changed as it rapidly spread cat-to-cat in the shelter. With subsequent cat passages, the infecting virus started developing mutations in one of the coronavirus-related genes associated with production of a protein called 3c. Coronaviruses that do not produce normal 3c protein will no longer infect enterocytes and are therefore not shed in the feces. This same type of mutation is common to the FIP viruses isolated from cats with enzootic disease. This occurrence of 3c gene mutations was probably the major reason why the Taiwanese outbreak was self-limiting, and not just because a simple quarantine was initiated.

Q: We can all understand that cases of FIP commonly occur in large catteries where FECV is prevalent, and where there is a genetic relationship between affected cats. However, there are also cases where 3-4 genetically unrelated cats in the same household (not a large cattery) develop FIP one after the other during a time period of 6-12 months. Assuming that all of these cats developed FIP due to internal mutation of FECV, this seems a bit strange considering that only a small proportion of cats are supposed to go on and develop FIP after FECV infection. How do you explain this?
A: The morbidity to FIP can range from less than 1% to more than 5-20% in the enzootic form, depending on many factors. In catteries, genetics play an important role, but it is not the sole factor. With random bred cats, non-genetic factors are even more important. We know that the age at exposure to FECV and stressors of many types that occur during primary FECV infection (starting around 9 weeks) are very important. Resistance develops with age and the younger they are exposed the more likely to come down. The problem is that in shelters and catteries the exposure occurs much earlier in life than if cats are running free at a reasonable density. There is no accident that over 70% of FIP cases come from catteries, shelters and kitten/cat foster and rescue organizations. We also know that 20% or more of FECV infections can generate FIP-causing mutants, but yet only a fraction of cats get sick. This means that many cats actually resist the disease. The question then becomes - why do some get the disease when others do not?

Q: Which are the most important stress factors that can influence the development of FIP in young cats?
A: In principle anything that interferes with a kitten’s immune response in that critical period between 9 weeks when they usually first see FECV and 16 weeks or so when their immune system really starts to become mature can potentially tip the balance towards disease. Vaccinations, deworming, early neutering, moving to a new family – all of these things can affect the immune system, plus all of the common kittenhood respiratory and enteric disorders that occur during this period. However, it is impossible to weight the influence of one or another, or any combination. I like to use the term “perfect storm” from the famous movie. You get FIP when enough bad things come together at the wrong time.

The Bottom Line - House your cats in small groups. Do not stress them when they are young. Protect kittens from encountering FeCoV until their immune system is strong and don't inbreed.

Saturday, 1 March 2014

Preventing FIP is simple

"God grant me the serenity to accept the things I cannot change, the courage to change the things I can, and the wisdom to know the difference."Reinhold Niebuhr

What really really makes me mad about FIP is the complacency in the cat owning community since it is supposedly a coronavirus mutation confined to the unlucky individual cat and furthermore not transmissable to humans; FeCoV (feline coronavirus) is an oral fecal thing and has a very short persistance outside a host therefor theoretically easy to beat. No FeCOV = no FIP. Worse things have been banished with no more exciting weapons than soap, clean water and flushing loos.
"FIP is pretty rare in housecats who are not exposed to other cats, occurring in roughly 1 in 5000 cats in this situation. FIP is fairly common in catteries in which feline coronavirus carriers are present, occurring in about 1 in 20 cats in this situation." 
Read more: Feline Infectious Peritonitis( FIP) and Feline coronavirus (FeCoV) - VetInfo 
What really really scares me about FIP though is the breeding of virulence by letting it cycle multiple times through kitty hosts who are unaturally confined indoors with an abnormal number of other potential hosts, who are to boot, probably immune suppressed through poor diet and inbreeding. "Wu Lien-teh, moreover, suggested that virulence increases in the course of an epidemic. Dongzheng Yu conducted a series of experiments in rats to test this idea. He injected them with a strain of plague from wild rodents; the injected rats were not easily infected and died slowly. Next, he withdrew plague bacteria from those rats and injected it into others, and on and on. Eventually, this serial passage produced a plague strain so lethal that rats injected with only a tiny amount died rapidly, suggesting that the strain's virulence had markedly increased."

The knee jerk reaction, massive culling, as happened to the civet cats in China during SARS, is probably counterproductive - civets have low immunity anyway, why ruin the genepool further?
 "The last thing we should do is to take it out on the bats, because the evidence suggests that they have carried this coronavirus for thousands, perhaps millions, of years; only recently has it emerged in a big way, and it was human behaviours that made the difference."
We need to change our behaviours now, because this is the one thing about FIP we can control while still dreaming of some miracle pill - and it's entirely DOABLE to eliminate FCoV infection from a cattery

Tomten - thoughts on inflammation

"drink the wine drink the wine- music, good friends, I'm not dyin' today" ~ Tori Amos

Tomten has been doing the Lazarus cat dance back from the brink for past eight months. He was heading downhill in late June and a surgery was performed hoping the granulomas were from a foreign body like string. However he crashed after the surgery and was very poorly for several weeks.
"Tomten continues to fight but is growing steadily weaker. He has taken to spending the entire day in a pile of stuffed animals in the kids play room. My husband can get him to eat a little bit. He is becoming wobbly on his feet. My husband is still hopeful and when he eats I am too but in my gut I think he is in his final weeks."
But his vets didn't think he was in pain, didn't toss in the towel and a week later on July 26th he turned the corner with last ditch antibiotics, steroids and high energy paste.
 Cassie wrote - "I am scared to to even post this in case it jinxes us but Tom has had a great two days. Since going on the last ditch antibiotics and back on pregnazone (sic) and the high calorie paste he is feeling so much better. He is eating!! He is hanging out with us and Gizmo instead of hiding in the stuffed animal pile. When he got sick last year we did 3 things. Interferone, prednasone, and a course of antibiotics for the herpes which was bad. Since surgery Tom was off the pregnazone and he had antibiotics on the operating table but none since. Keeping my fingers crossed he is turning a corner but too scared to hope. Is it possible he has 18 lives?"
I wonder if I've been underestimating the support antibiotics can provide an ailing cat - even if it's not the primary illness, knocking down the numbers of bacteria multiplying out of their normal range due to host debilitation, may allow the cat enough space to muster his reserves for the fight. "lipo polysaccharides (LPS ) from many bacterial species will initiate acute inflammatory responses in mammals". Maybe we should have tried harder with Mishka's lump.

So his ultrasounds didn't show any other lumps - he went back to happy and active. And Cassie was back to square one diagnostically.
"He continues to do well since the antibiotics and the return to Pred. I caught him playing kitty smack down with Gizmo last night first time in 3 months. I don't know who was happier Gizmo or me. I think Gizmo was letting him win since he out weighs Tomten 3 to 1 at this point. Tomten couldn't have a more loving brother. Now that I have him back again my thoughts are turning to how do I keep him alive and delay the granulomas from coming back. I started doing some internet research trying to figure out what besides FIP causes granulomas and responds so dramatically to antibiotics and prednisone. I came across Inflammatory Bowel disease (IBD). The literature says its rare but can cause granulomas."
 Some informational links and my thoughts on IBD and inflammation:
  • - My gut feeling (haha a pun) is that Feline Irritable Bowel its not far off human IBD. What you eat determines the gut microbiome. We have a little human friend who had to have a fecal transplant to get rid of his awful colitis. He is a very sick boy who is now off all his meds! Anyone with Crohn's disease or colitis who wants to get cured contact Dr Borody in Sydney.
  • Although i dont have direct cat experience with IBD per se I noted our other pets have better skin on a proper raw diet, which I imagine reflects the state of the gut as it is basically the same as skin - both are made of epithelial cells. Mishka was the big diet fail - i always thought she'd come a cropper on dry food diet but figured (wrongly) I had time to transition her to a 'better' diet. Wrong again - commercial petfood is just wrong, I had no idea it was all so dreadful until she got ill. Now i know even the tinned food, though 'complete', is still highly inflammatory.
  •  - carageenan is seaweed - not meant to be eaten by cats but it's the thickener in most commercial petfood. It is known to incite inflammation, in fact it's used experimentally to do just that when you need to make a wound to test a cure on!  I have no idea why they dont use gelatin instead, which is anti inflammatory and being connective tissue supplies all the right things for building connective tissue for both humans and animals