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Introduction
Feline Infectious Peritonitis (FIP) is an uncommon,
fatal viral disease of cats. It is caused by infection
with feline coronavirus (FCoV). There is much confusion
and much misinformation about the disease. I hope the
information contained in this article addresses most of
the concerns and questions that commonly arise,
especially when a veterinarian suggests that your cat
may have the disease.
Transmission and Development of FIP
Coronaviruses can affect many different species. They
cause intestinal and respiratory disease in dogs and
pigs, and are a cause of the common cold in humans.
Feline coronaviruses are related to these other
coronaviruses. The most common form or “biotype” of FCoV
is the enteric (intestinal) form of the virus. This form
is easily transmitted between cats. Cats become infected
by the fecal-oral route. In other words, FCoV is shed in
the feces of one cat, and somehow is ingested by another
cat. After the virus is ingested, the virus replicates
(i.e. reproduces, making many copies of itself) within
the cells that line the intestinal tract. When cats
become infected with this form of the virus, they
usually show no overt clinical signs. Occasionally,
infected cats will get transient, self-limiting
diarrhea, probably as a result of the damage to the
intestinal cells during viral replication.
Most cats, when they become infected, will shed the
virus in their feces for a period of time, usually a few
months, and then stop. Infected cats produce antibodies
to the virus in response to the infection. Cats may
become re-infected with FCoV in the future, and begin
shedding again, if they encounter more virus. Again,
most encounters are via the fecal-oral route.
Although most infected cats shed the virus for a few
months and then stop, a few become persistent shedders,
releasing the virus in their feces continuously.
Coronaviruses have an important characteristic: they are
fairly prone to genetic change, and seemingly harmless
coronaviruses can mutate into a variant virus that may
be more pathogenic than the original virus. This, in
fact, is how clinical cases of FIP are thought to arise.
The relatively benign intestinal coronavirus mutates
into a new form type of coronavirus, one that can leave
the intestinal tract and cause problems in many
different organ systems. This mutated coronavirus is now
the deadly, evil FIP virus.
The FIP virus triggers an immune response by the body.
The immune response, however, is ineffective and
actually makes things worse. Antibodies produced against
the FIP virus do not neutralize the virus. The
antibodies bind the virus, and these antibody-virus
complexes circulate in the bloodstream eventually
settling down and accumulating in the walls of the blood
vessels where they trigger an intense and harmful
inflammatory reaction. These inflammatory lesions can
occur in virtually any body system, accounting for the
wide range of clinical signs seen in FIP. Normally, when
an antibody binds a virus, an immune system cell called
a macrophage will gobble up the antibody-bound virus and
destroy it. Macrophages, however, don’t destroy the FIP
virus, however. Instead, they gobble up the virus and
then transport it to other parts of the body,
disseminating the disease throughout the body.
Which cats are affected?
Most cases of FIP occur in young cats. In fact, many
cases probably occur right after their first infection.
This likely has to do with the fact that coronaviruses
are prone to mutation. Mutations are more likely to
occur when viruses are reproducing themselves, and the
highest amount of viral replication occurs right after
infection, increasing the risk of the benign intestinal
coronavirus transforming into the evil FIP coronavirus.
Other stressful factors are often present in young cats,
such as an immature immune system, recent re-homing,
neutering, vaccination, and perhaps concurrent illness.
The peak age for development of FIP is between 6 months
and 2 years. Although youngsters fall victim most often,
cases are also seen in older cats.
Infection with FCoV is common in cat populations
everywhere. Approximately 25 to 40% of household cats
are infected with FCoV. In breeding catteries and other
large colonies, the number rises to 80 – 100%. Despite
this high level of exposure to the virus, FIP is a
relatively uncommon disorder. This is because most
infections, as stated above, are with the fairly
harmless strain of FCoV – the one that produces only
mild diarrhea. Cats from breeding catteries and other
large multicat households show a higher prevalence of
FIP, and this is a reflection of the fact that exposure
to FCoV is hard to avoid. In a multicat environment,
there may be a few cats who are carriers that
continually shed the virus in their feces, reinfecting
other cats in the household who also shed the virus,
even if only intermittently. In fact, studies have
suggested that as few as six cats sharing the same
environment are enough to maintain persistent FCoV
infections. So, in a multicat environment, the more cats
that are chronically shedding FCoV, and the more cats
that become reinfected, the higher the risk of FIP
developing. Other factors are probably involved, such as
genetic susceptibility. A study of all cats diagnosed
with FIP over a 16 year period at North Carolina State
University revealed that purebred cats were
significantly more likely to be diagnosed with FIP, and
that Abyssinians, Bengals, Birmans, Himalayans, Ragdolls,
and Rexes have a significantly higher risk, whereas
Burmese, Exotic Shorthairs, Manxes, Persians, Russian
Blues, do not appear to be at increased risk. In colony
situations, the incidence of FIP is typically 5%,
although this number can vary widely between different
colonies. It is not uncommon to see FIP develop in
several or al of the kittens from an individual litter
over a period of time. In households containing one or
two mature cats, the incidence of FIP is very low,
perhaps only 1 in 5000.
What are the signs?
Clinical signs associated with FCoV infection are mild –
a little diarrhea, perhaps a little vomiting, for a few
days duration. FIP, however, can present with a wide
variety of clinical signs. There are no clinical signs
associated with FIP that are unique for this disease. In
general, the disease presents itself in one of two major
forms: the effusive (“wet”) form, and the non-effusive
(“dry”) form.
As stated above, when the immune system produces
antibodies against the FIP virus, the antibodies, rather
than neutralize the virus, will bind the virus, and then
these antibody-virus complexes circulate in the
bloodstream eventually settling down and accumulating in
the walls of the blood vessels where they trigger an
intense and harmful inflammatory reaction. The
inflammation of the blood vessels causes protein-rich
fluid to leak through the walls of the blood vessels and
accumulate in body cavities. This accumulated fluid is
called an effusion, and is the hallmark of effusive or
“wet” FIP. On the other hand, the FIP virus can induce
an inflammatory response that leads to the formation of
clusters of inflammatory cells (called granulomas)
accumulating in a variety of organs and structures. The
most common sites for granulomas to develop are the
abdominal organs such as the liver, kidneys, intestines,
and lymph nodes, as well as the eye and the nervous
system. The clinical signs that develop depend on which
organ or body system is affected. Effusions are not seen
in this form of FIP, hence the name non-effusive, or
“dry” FIP. “Wet” FIP is more common than “dry” FIP, and
probably accounts for 60 – 70% of FIP cases.
Early in the course of the disease, the clinical signs
of both wet and dry FIP tend to be non-specific and
include fever, lethargy, poor appetite, and weight loss.
The vague nature of these signs is what makes FIP so
difficult to diagnose early in the course of disease. As
the disease progresses, other clinical signs may become
more apparent, perhaps allowing the disease to be
categorized as the effusive (wet) or non-effusive (dry)
form.
Accumulation of fluid in the abdomen, often causing
dramatic abdominal distension, is an obvious
manifestation of wet FIP, and is the most common place
that fluid tends to accumulate. Less commonly, the fluid
will be present in the chest, causing breathing
difficulty. Now and then, fluid will be present in both
cavities. Occasionally, fluid will accumulate in the
pericardial sac (the membrane that surrounds the heart),
causing cardiac dysfunction. In many cats with the wet
form of the disease, the eyes and the central nervous
system will be affected. The liver is commonly affected,
sometimes causing jaundice.
Clinical signs of the dry form of the disease can be
very vague, making diagnosis a real challenge.
Persistent fever that doesn’t respond to antibiotics,
progressive weight loss, and lethargy tend to be the
main signs. As the disease progresses and granulomas
develop, other clinical signs will develop depending on
the organ that is affected and the degree of
involvement. The FIP virus has a predilection for the
eyes and central nervous system and signs of neurologic
dysfunction (uncoordinated walking) or eye inflammation
are not uncommon.
How is it diagnosed?
FIP is one of the most difficult feline disorders to
diagnose. The vague clinical signs early in the course
of the disease are seen in many other feline illnesses
as well. There are no routine laboratory tests that can
definitively confirm one’s suspicions of an FIP
diagnosis. Instead, one must evaluate the historical
results, clinical signs, physical exam findings and
laboratory tests. At this point, one may conclude that
they have enough evidence for a presumptive diagnosis of
FIP. In cases where the diagnosis remains in doubt,
tissue biopsies may ultimately be necessary to make a
certain diagnosis.
Historically, cases of FIP are more common in young cats
(less than 2 years), purebred cats, and cats from
multicat environments.
Routine laboratory tests won’t prove or disprove the
diagnosis, but may offer evidence to support or refute
one’s suspicions of FIP as the cause of the clinical
signs. A complete blood count often shows a low
lymphocyte count and high neutrophil count. These are
very non-specific changes and are seen in many other
illnesses.
A serum biochemistry panel also tends to show
non-specific changes, however, elevated globulins are a
common and important finding, seen in 50 to 80% of FIP
cases. . Hyperproteinemia is usually present, the
elevation being due to increase in globulins. Albumin
levels may be normal, although frequently they are low
or low-normal. Because the liver is an organ that is
frequently affected in cases of FIP, elevated liver
enzymes and high bilirubin levels are not uncommon.
Coronavirus serology – measuring the level of antibodies
against coronavirus in the bloodstream – is common and
very misunderstood test. A positive test result simply
confirms that the cat has been exposed to a strain of
FCoV. Excessive reliance should not be placed on this
test. It holds no more value than results of routine
hematology and serum biochemistry. Keeping I mind that
25 to 40% of the general cat population and 80 – 100% of
cats in multicat households are seropositive for
coronavirus, a positive result must be interpreted
cautiously. As a general rule, cats with FIP tend to
have higher FCoV antibody titers, but there is much
overlap in titers between healthy cats that were simply
exposed to FCoV vs. sick cats currently suffering from
FIP. Again, excessive reliance should not be placed on
this test. In fact, there have been cases of FIP in
which the coronavirus antibody test showed a lack of
detectable antibodies. To summarize: low or medium
levels of coronavirus antibodies have no diagnostic
value because the virus is so ubiquitous. Negative
levels suggest a cat is unlikely to have FIP (although
about 10% of cats with FIP will have no detectable
antibody); and very high levels of antibody offers
support for a diagnosis of FIP, but a strongly positive
test is not, in and of itself, diagnostic for the
disease.
A valuable diagnostic test is the evaluation of
effusions in cases of wet FIP. These effusions tend to
be “straw-colored” in appearance and is thick, with a
sticky feel to it. The protein content is high, with
globulins making up more than 50% of the proteins. There
are few diseases that produce effusions with such
characteristics. Taken with other supportive evidence,
an effusion of this type can provide strong evidence for
a presumptive diagnosis, especially if this type of
effusion is found in more than one body cavity.
Detection of coronavirus particles within the cells that
are found in the FIP-induced effusions offers very
strong support for a diagnosis (in one study, a positive
test was 100% predictive for FIP), but this type of test
tends to be performed in research laboratories and most
commercial laboratories do not offer this test.
Polymerase chain reaction (PCR) has become a popular
high-tech method for detecting the presence of
infectious organisms. It does this by detecting minute
quantities of viral or bacterial DNA and amplifying it
to millions or billions of copies so that it can be
detected by a routine laboratory method. Like every
other test in veterinary medicine, PCR has its pitfalls,
and when it comes to FIP, the PCR suffers from the same
limitations as antibody testing – it is unable to
distinguish which strain of FCoV to which the cat has
been exposed. Those PCRs which claim to have detected
the mutation which differentiates the harmless
intestinal FCoV from the virulent FIP coronavirus have
never been validated by the scientific community.
If significant doubts remain concerning the diagnosis of
FIP, a truly definitive diagnosis can be achieved
through biopsy of appropriate organs. Biopsy specimens
may be obtained via exploratory surgery, or by
percutaneous needle biopsy, using ultrasound guidance if
necessary. When examined under a microscope by a
pathologist, affected tissue samples demonstrate
pyogranulomatous inflammation, a characteristic type of
inflammation seen in cases of FIP. If there is still
doubt as to whether FIP is the cause of the
inflammation, additional confirmation can be pursued
through immunohistochemistry – using special tissue
staining procedures – to detect the presence of FCoV
within the biopsy specimen.
Is there any treatment?
FIP is progressive and fatal. Cats with FIP tend to
succumb to the disease rather quickly, in a few days or
weeks. Wet FIP tends to progress faster than dry FIP.
Treatment is generally symptomatic and supportive.
Nutritional support, antibiotics, and corticosteroids
may produce a temporary alleviation of clinical signs,
but the disease invariably progresses. In 2004, a report
was published that described the use of recombinant
feline interferon and glucocorticoids for the treatment
of FIP. Twelve cats with FIP underwent therapy. Four
cats succumbed quickly; four cats showed a partial
remission (surviving for two to five months), and four
cats showed a complete remission (survival time greater
than 2 years). The four cats that showed long term
survival were older cats – between the age of 6 and 16 –
and all had the wet form of the disease. Although the
number of cats in the study was small, the results were
encouraging in that they suggest an apparent therapeutic
effect of recombinant feline interferon in select cases
of FIP. However, the high cost associated with feline
interferon, and the fact that it is only available in
Japan, the UK, and the EC countries may be an obstacle
for treatment. Ultimately, nearly all cats diagnosed
with FIP are euthanized to alleviate suffering. In terms
of contagion, the fact that there have been reports of
FIP outbreaks in individual colonies of cats suggests
that direct transmission of the FIP-causing coronavirus
is occasionally possible, however, the FIP virus does
not appear to be commonly transmitted in nature and
usually dies out when the affected cat dies from the
disease.
Prevention and Control
Because the virus causing FIP is an uncommon mutation of
a widespread virus, it can be difficult to prevent and
control. The most effective management strategies center
around preventing and controlling the prevalence of the
underlying infection with FCoV. To prevent FIP in
household pets, one should avoid obtaining cats from a
source where many cats are housed, and try to obtain
them from a place where cats or kittens are kept in
small stable groups. To put it more simply, one should
obtain healthy kittens/cats from a healthy background.
One should avoid having large numbers of cats sharing
one living space. Household cats kept singly or in small
groups are unlikely to develop FIP.
In breeding catteries, one can attempt to control FIP by
reducing the incidence of FCoV infection, or one can try
to completely eradicate FCoV within the colony.
Eradication of infection, however, is very time
consuming and laborious. Maintaining a FCoV-free colony
can be quite a challenge, given the ubiquitous nature of
FCoV infections. A more realistic approach is to
consider eliminating FCoV infection in kittens born into
the environment where FCoV is present. If a pregnant
queen is isolated from other cats one to two weeks
before giving birth, and is then kept isolated with her
kittens while practicing good hygiene procedures to
prevent environmental spread of infection to the
kittens), most of these kittens will remain free of
infection. Testing kittens for FCoV antibodies before
they are weaned will yield invalid results because
kittens derive their antibodies from their mothers, and
a positive result merely confirms that the mother was
exposed to FCoV. After weaning, however, the queen can
be removed and the kittens still kept isolated and
tested at 12 – 16 weeks of age for antibodies to FCoV.
If the litter tests negative, the isolation procedure
has been successful. These kittens are FCoV negative and
would theoretically be incapable of developing FIP since
they do not have the coronavirus in their body. The
isolation procedure sometimes fails if the queen herself
is shedding FCoV in her stool and passes it to the
kittens. This might be avoided if the kittens are weaned
early (at 5 to 6 weeks of age), because the antibodies
against FCoV that the kittens obtain from the mother may
prevent the kittens of acquiring the infection. Raising
FCoV-free kittens requires considerable commitment from
breeders.
Good hygiene is always important when trying to minimize
the prevalence of FIP. Bearing in mind that the
fecal-oral route is thought to be the major way in which
the virus is spread, some practical control measures
that have been suggested include having enough litter
boxes (ideally, one for every two cats), keeping litter
boxes away from places where food and water are kept,
and keeping all litter boxes very clean. Feces should be
removed at least once daily, and litter should be
changed as often as practical. Cats should be kept in
small stable groups. Regular brushing of the hair coat
(especially longhaired cats) is recommended to remove
any feces or litter that might get stuck in the fur.
A commercial FIP vaccine is available, however the use
of the vaccine is controversial. The vaccine is
administered intranasally (i.e.drops in the nose).
Different studies of the vaccine have yielded very
different results, and the efficacy of the vaccine
remains questionable. The American Association of Feline
Practitioners and the Academy of Feline Medicine, in
their regularly published guidelines for feline
vaccination, currently do not endorse the routine use of
the FIP vaccine at this time.
Updated
3/28/06 |
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