FIP
Feline infectious peritonitis
FELINE INFECTIOUS PERITONITIS (FIP): Update 2007
Monday, October 1, 2007
![Jacqueline Norris BVSc (Hons), MVSt, PhD, Grad Cert Educ (Higher) -Senior Lecturer in Veterinary Microbiology -- Faculty of Veterinary Science - University of Sydney - jnorris@mail.usyd.edu.au
Extensive research efforts worldwide has led to a new understanding of Feline Coronavirus
(FCoV) infection and FIP but has produced an even greater number of questions that remain
unanswered. Currently there is no effective prevention or treatment for FIP. Equally, there is no
method of accurately predicting which cats are at risk of developing the disease. The
invariably fatal consequences, lack of predictable disease patterns, ineffective treatment
regimes and the significant emotional and financial impact of FIP makes it a formidable
disease.
Background
FIP is a fatal immune mediated disease of
wild and domesticated cats (Felidae)
caused by mutant strains of Feline
Coronavirus (FCoV). It is one of the most
important causes of death in young cats. It
occurs in cats of all ages but most
commonly those under 3 years.
The disease was first described in 1963 by
Holzworth as a syndrome known as
“chronic fibrinous peritonitis” but the
name, along with the current name of FIP,
is limiting in its description of this incredibly
variable disease. FIP is now known to
manifest as varying degrees of
1) systemic serositis (inflammation of the
serous membranes eg. the superficial
surfaces of the abdominal or thoracic
organs leading to wet FIP),
2) vasculitis (inflammation of the blood
vessels) and
3) disseminated pyogranulomas (many
areas of inflammation in body organs,
consisting of the white blood cells called
macrophages and neutrophils).
The first reported appearance of FIP in
Australia was in 19741, 2 but despite the
anecdotal evidence of its frequent
occurrence in Australia, there has been a
conspicuous absence of peer-reviewed
reports until a recently review of 42 cases.3
Viruses within the family Coronaviridae, are
known for their tendency to mutate
frequently during viral replication
(reproduction). Feline coronaviruses are
typical in this regard. The exact nature of
the FIP inducing mutations are still
unknown but are likely to be complex. The
3C, 7B and spike genes are now
considered to be most important in the
development of FIP-causing mutant FCoV
although the mutation occurs at various
points along these genes. A key feature of
the mutant FCoV is the ability to replicate
in large numbers in a type of white blood
cell known as the macrophage (also
known as monocytes when circulating in
the bloodstream). It is on this principle that
the only reliable diagnostic tests for FIP are
based.
To complicate matters further, the role of
the immune system in protecting against
disease in some animals, while contributing
to the disease in others, is another poorly
defined issue in the development of FIP.
Genetic susceptibility
FIP is reported to occur more frequently in
cats from catteries, boarding facilities and
multicat households.4 While no breed
predisposition has been firmly established,
certain bloodlines and matings within a
breed may be at greater risk.5 The
incidence of FIP in purebred catteries
increases in proportion to the number of
animals kept in that facility. Environmental
factors, however, are not the sole
contributor to FIP susceptibility. Foley and
Pedersen (6) determined that FIP
susceptibility was a partially heritable trait,
with close relatives of affected cats within
four Persian and one Birman catteries
being significantly more likely to die of FIP
than unrelated cats.

Figure 1: Inbreeding in cheetahs has led to an
increased susceptibility to infectious diseases
including feline infectious peritonitis.
Of the non-domestic felids, cheetahs have
been found to be especially susceptibility
to FIP. Inbreeding in this species has
predisposed them to diseases involving a
variety of infectious agents, including
FCoV.7 Conversely, cats from some
Abyssinian bloodlines have been reported
to have significantly longer survival times
after experimental challenge with virulent
FIP strains than other breeds, suggesting an
inherited resistance to FIP.6, 8
A retrospective study in Australia9 found
that purebred cats were over represented
in the FIP cohort while DSH were under
represented. Within the purebred cats,
Burmese, Australian Mist, British Shorthair
and Cornish Rex cats were significantly
over-represented, while Persian cats were
under-represented, dispelling the
explanation of husbandry practices being
the only contributor to the incidence of
FIP. The overrepresentation of certain
purebreds, most notably the Burmese and
BSH cats has been mirrored in the
demographics of confirmed cases of FIP
received via clinical samples (tissues and
effusions) submitted to our diagnostic lab
over the past 3 years from all over Australia
(Veterinary Diagnostic Pathology Services,
The University of Sydney). In our
observations, other breeds or at least
breed lines have also been noted as
‘breeds of interest’ due to an increase
number of cases of FIP. These breeds
include the Birman and Ragdoll.
Conversely we now rarely see cases of FIP
in Australian Mists. Our research team is
currently investigating the differences in
the immune response between different
breeds of cattery-confined cats to gain an
understanding of factors that make some
cats more susceptible to FCoV infection
and the disease FIP.
While FCoV antibody titres are unable to
predict which cats will go on to develop
FIP, it is widely accepted that the
magnitude of the FCoV antibody titre
broadly reflects the viral load within a
given cat.10, 11 In other words, a cat with a
high antibody titre to FCoV will have a
high FCoV load in its body and is likely to
be shedding virus in the faeces. Although
this is not a direct predictive relationship,
some researchers have speculated that
certain cats with persistent and/or high
FCoV antibody titres, given the right host
(cat) susceptibility, are at a greater risk of
developing FIP due to the greater risk of
viral mutations occurring.12, 13 The exact
titre that constitutes a ‘high’ titre varies
markedly depending on the test used.
Kummrow and colleagues suggested the
guideline listed in the table below.14
Recent studies in Australia15-17 have further
highlighted a possible role of genetics in
the development of this immune
mediated viral disease. In serum antibody
surveys conducted in household and
cattery confined cats it was found that
certain cat breeds had significantly higher
antibody titres than other breeds.17 In an
Australia wide retrospective study of 637
cats,16 the FCoV antibody titres of Siamese,
Persians, DSH and Bengal cats were
significantly lower than that of British
Shorthair, Cornish Rex and Burmese cats.
In a Sydney based serum antibody study of
household pet cats,17 the antibody titres of
DSH, Persian, Siamese and Devon Rex cats
were significantly lower than that of
Burmese, BSH, Abyssinian, Birman, Ragdoll,
and Russian Blue. The significant
relationship between the breed of the cat
and the FCoV antibody titre, especially in
those breeds identified to be at greater risk
of developing FIP, further supports the
notion that breed (genetic) related
differences exist in the immunological
response to FCoV infection.
Considerable work into the differing
immune responses to FCoV and the role of
genetics in controlling these immune
responses is required if we are to have any
chance of controlling this disease.
Transmission
FCoV infection is common in cattery-
confined cats (80-100%) and pet cats (20-
35%) worldwide due to faeco-oral
transmission and environmental resistance
of the virus. While it is endemic in many cat
populations, the outcomes of infection are
variable. Understanding the modes of
transmission of Feline Coronaviruses
requires knowledge of the virus location
and its ability to infect tissues within the
body.
FCoV is a fairly fragile virus that is
destroyed by most household disinfectants
and detergents. It can however survive up
to 7 weeks in dry conditions eg dried
faeces, carpet etc. The most common
method of FCoV transmission is via virus-
infected faeces, although in the first few
hours to days of infection it can be shed in
the saliva and respiratory droplets. Usually
kittens are infected with FCoV from their
mother or other FCoV excreting cats, at
the age of 6 to 8 weeks, when their
maternal antibodies wane. Maternal
antibodies are thought to protect kittens
from FCoV infection until this time, as most
kittens that are removed from an
environment of FCoV shedding cats at 5 to
6 weeks do not become infected.(10)

Figure 2: Faeco-oral transmission of feline
coronaviruses is facilitated by the use of communal
litter trays.
Replication of the feline coronaviruses in
clinically normal cats occurs mainly in the
intestinal lining (enterocytes). However
these viruses are known to infect
monocytic cells, circulate in the blood and
spread systemically even in clinically
normal cats,18, 19 although their ability to
Shedding of infected enterocytes from the
intestinal villi means that virus is shed in the
faeces and cycles through the feline
household via faeco-oral route. Testament
to this is the finding in Australia (and many
other parts of the world) that 98% of cats
within catteries are infected with FCoV,
and only 34% of pet cats are infected, with
cats in single cat households significantly
less likely to be infected.15, 17 The interesting
finding in our studies has been the
variation in antibody titres and likely viral
loads between cats in the same cattery
environment. For example, in one cattery
the antibody titres ranged from 1:400 to
1:25,600 and this variation was not related
to the age of the cat.
Many apparently healthy cats who are
persistently infected with FCoV play an
important role in recycling FCoV in
multicat environments. FCoV shedding
cats produce many millions/billions of virus
particles in their faeces, some of which
can be spread to the environment during
digging of litter (Figure 2).
There is considerable debate over how a
persistently FCoV infected cat develops
FIP. One theory is that a mutation of the
virus occurs within an individual cat. The
formation of mutant strains is thought to
confer the ability to infect large numbers
of macrophages and reproduce large
volumes of the virus. This theory is
substantiated by recent work of Kipar and
colleagues20 which showed (using real
time RT-PCR) that cats with FIP have
considerably larger viral loads in the areas
of the body that produce blood cells (eg
spleen, lymph nodes) than healthy FCoV
infected cats. These mutant forms of FCoV
are thought NOT to shed faecally but are
contained within the internal structures of
an infected animal. Greater than 40% of
cats with FIP will shed the enteric based
FCoV, however the mutant forms of the
virus (previously called FIPV) has not been
found in the secretions or faeces from cats
with FIP to date. Therefore transmission of
mutated FCoV from one cat to the next is
considered unlikely under natural
conditions. It is theoretically possible,
although not substantiated by current
research, that cats with FIP lesions in the
kidneys or intestines may shed virus. This
theory has been put forward to explain
some reported “outbreaks” of FIP.
Alternatively, the existence of
immunocompetent carriers of the mutant
virulent form of FCoV may explain these
infrequent occurrences. Neither of these
theories have been substantiated. When
dealing with FIP within litters of kittens it is
important to also consider the role of cat’s
susceptibility in the development of
disease as frequently only certain kittens
within a litter are affected. It is important
NOT to condemn litter mates of kittens
affected by FIP. We have many examples
of litter mates who have lived long healthy
lives despite the demise of their litter mate
and in many cases while cohabitating with
the affected kittens.
One final important point about
transmission is that veterinarians when
dealing with the effusions of cats with wet
FIP or performing post-mortems within the
clinic should be aware that these fluids
and tissues are highly contagious to other
cats and pose a significant threat for the
subsequent development of FIP if hospital
cats are exposed to the virus.
Development of Disease
The development of FIP is still a poorly
understood disease process. Most of the
pathology seen is caused by the cat’s
immune response to the virus. Two theories
have been proposed to explain
subsequent events. One theory is that
mutant FCoV infected macrophages exit
the blood vessels and enter the tissue. The
virus attracts antibodies and certain
proteins known as complement. More
macrophages and neutrophils (two types
of white blood cells) are attracted to the
tissue, leading to the development of
pyogranulomatous lesions. An alternative
theory suggests that circulating immune
complexes deposit on the blood vessel
walls, leading to the release of substances
that cause the lining of the blood vessels
to leak fluid. This allows FCoV infected
monocytes to enter the tissue. Release of
further substances from infected and dying
monocytes stimulates further blood vessel
leakage and the development of high
protein fluids into the abdominal/chest
cavities in some cases. The immune
mediated vasculitis and the formation of
pyogranulomas are the key features of FIP
seen in microscopic sections.

Figure 3: This section of liver has been stained using the
specialised technique known as immunohistochemistry. On the outside of the picture are normal liver cells, while the concentration of cells in the centre shows a typical
pyogranuloma . The brown staining cells are FCoV infected
macrophages.
Clinical Presentation
The clinical presentations of FIP are
variable and often complex, reflecting
variations in the virus itself, the nature of
the cat’s immune response and the
influence of environmental stresses.
Approximately 50% of all cats diagnosed
worldwide are less than two years old and
purebred cats are generally over
represented. Two broad forms of the
disease have been described across all
ages and breeds: “effusive” (wet) or “non-
effusive” (dry). Despite this apparent
division, these are not distinct disease
entities. Cats with non-effusive FIP may
develop effusions in the terminal stages of
disease and conversely, there are reports
of non-effusive FIP being preceded by a
subtle effusive form of the disease.
Typically, patients with effusive FIP have
high protein abdominal, pericardial
(around heart) and/or thoracic (chest)
effusion(s), fever, weight loss, anaemia
and elevated serum globulin levels,
although not all cats adhere to this
stereotype. The non-effusive form of FIP is
often more vague in its presentation with
non-specific signs including fever, weight
loss, and inappetance. Clinical signs,
beyond the non-specific, relate to the
tissues affected. Possibilities include liver,
kidney, pancreas, spleen, abdominal
lymph nodes, central nervous system
(CNS), gastrointestinal tract (GIT), eyes, skin
and heart. Usually more than one body
system is involved but occasionally only
one is affected e.g. CNS or GIT, and
clinical signs are restricted to this particular
system.
Studies in Australia (9) compared the clinical
presentations of FIP in Australia’s
geographically isolated cat population
with overseas reports. Significant features
of this study were i) the over-representation
of certain breeds (Burmese, Australian Mist,
British Shorthair, and Cornish Rex) and the
under-representation of other breeds
(Domestic Shorthair, Persian); ii) the
overrepresentation of males (2 to 1); iii) the
even age distribution of disease seen in
cats older than 2 years-of-age; and iv) the
presence of immune-mediated
haemolytic anaemia (red blood cell
destruction) in two cats in that study plus
three cats subsequent to the study.

Figure 4: The age distribution of cats presented with
feline infectious peritonitis in the study by Norris et al
2005.
Diagnosis
The difficulties in diagnosing FIP have been
a hot topic in feline medicine for many
years. Adopting traditional instruments of
infectious disease diagnosis (eg PCR,
serology) for FIP diagnosis and FCoV
infection control has led to ongoing
confusion for vets and unwarranted
euthanasia of cats. This has stemmed from
an incomplete understanding of the
dynamics of FCoV infection in cats and
the development of FIP. Diagnostic tests
for FIP must therefore rely on the biological
behaviour of the virus. A key feature of the
nasty mutant FCoV is the ability to
reproduce in large numbers in
macrophages and monocytes and it is on
this premise that the only reliable
diagnostic tests for FIP are based.
The clinical similarity between FIP and
many other feline diseases, coupled with
the non-specific nature of many of the
tests available, makes the definitive
diagnosis of FIP difficult even when the
diagnostic approach is broad and
thorough. While a cat presented with
elevated blood globulin (type of protein),
fever, and high protein abdominal and/or
thoracic effusion may be highly suggestive
of FIP, the variation in clinical
manifestations beyond this stereotype is
remarkable.
The advent of FCoV antibody titres and RT-
PCR (reverse transcription polymerase
chain reaction) has added to the
complexity due to the indistinct
differentiation between mutant FIP-
causing FCoV and those FCoV that are
unlikely to cause disease. While these tests
were first met with enthusiasm, it is now
known that it is not possible to differentiate
between the harmless and mutant forms of
the virus by RT-PCR or any FCoV antibody
test to date. This severely limits their use in
the diagnosis of FIP. Of greater concern is
the finding by several researches of FCoV
infection in the tissues of healthy cats
without clinical signs, highlighting the need
to exercise care to avoid over
interpretation. In other words, performing
RT-PCR, a technique that detects tiny
amounts of virus in tissue or blood cannot
be used for the diagnosis of FIP as many
normal cats have small amounts of FCoV
at these sites. Recent developments in the
detection of replicating FCoV within
circulating monocytes by RT-PCR however
look more promising.21 This is now available
in the USA but must be interpreted with
great caution and should not be used in
isolation.
Despite these limitations, FCoV antibody
titres are still used indiscriminately for the
diagnosis of FIP. A clinician must carefully
consider the environment and age of the
cat in question. For example a high
antibody titre from a young cat or a cat
from a multicat household is impossible to
interpret and is in no way helpful for the
diagnosis of FIP. Incorrect interpretation
can lead to incorrect diagnosis and
unnecessary euthanasia. To use the words
of Neils Pederen, an eminent researcher in
FIP, “more cats have died from the
misdiagnosis of FIP than from FIP itself”.
The detection of characteristic
microscopic changes within affected
tissue (biopsy or post mortem) has been
considered the only conclusive test for FIP
for a considerable time and detecting
virus within macrophages in the areas of
pathology using immunohistochemistry
allows definitive confirmation of the
diagnosis. In a disease process where the
treatment of choice is often euthanasia,
diagnostic accuracy is essential.
a) Serum biochemistry and haematology
The results of routine blood tests
(biochemistry and red and white blood
cell counts = haematology) found in
association with FIP are non-specific and
non-diagnostic. They may include
elevated serum protein due to elevated
globulin, increase bilirubin (may appear as
jaundice clinically), anaemia, and white
blood cell changes traditionally seen with
stress. These are found in many other
diseases. In addition, blood tests specific
to affected organs (eg kidney, liver) MAY
be elevated. Hartman and colleagues22
compared the value of certain diagnostic
tests in the largest study of FIP cases to
date and found that elevations of total
serum proteins above 80g/L was only 60%
specific for FIP. This highlights the need to
view elevated serum protein as being
supportive of a diagnosis of FIP and several
other diseases, but of limited diagnostic
value when in the normal range. In cases
in which total serum protein is elevated,
additional supportive evidence for FIP can
be gleaned from measurement of
albumin-globulin ratios, γ-globulin
concentrations and α1-acid glycoprotein.
None of these tests are conclusive and are
considered merely supportive or
circumstantial evidence (not enough to
convict a cat of FIP).
While blood profiles can provide essential
baseline information in the investigation of
sick cats, clinicians cannot exclude
disease in certain body organs simply due
to the absence of abnormal findings. In
our retrospective study of cases, some cats
with extensive pathology in the kidney or
liver had normal serum biochemical test
results.
b) Measuring FCoV antibody titres
The difficulties in interpreting antibody titres
of FCoV have led to widespread
acceptance that diagnosis of FIP by
antibody titres is neither possible nor
appropriate. Despite this, antibody titres
continue to be given undue emphasis in
the diagnosis of FIP. The antibody titre to
FCoV in cats with FIP varies according to
the nature of the clinical syndrome. There
is considerable variation in the reported
magnitude of anti-FCoV antibody titres in
cats with confirmed FIP, with considerable
overlap with healthy patients, making
interpretation difficult. Indeed, a negative
antibody titre alone cannot rule out a
diagnosis of FIP, while a high FCoV
antibody titre certainly does NOT confirm a
diagnosis of FIP. The emergence of tests
that claimed to measure antibodies
against mutant FCoV alone became
popular but their validity was NEVER
supported by peer reviewed publications
and they are now considered of no
greater value than other antibody tests.
The gold standard for measuring antibody
levels to FCoV is by indirect
immunofluorescence (IFA), a test that is
now available in several diagnostic
laboratories in Australia. Hartmann22 has
reported that cats with antibody titres of
1:1600 had a very high probability (94%) of
having FIP, however it is noteworthy that
this study compared cats with FIP to sick
cats with diseases clinically similar to FIP.
Healthy cats from multicat environments
were not included in that study and the
authors of that paper comment that a
high titre from a cat in a multicat
environment is not predictive of FIP due to
the high level of FCoV in those
environments.23 In addition, the method
used in that paper is different to those
used in Australia. Currently all labs in
Australia use a method of indirect
immunofluorescence that involves feline
cells infected with a FCoV (type not
always specified). Studies in Switzerland by
Kummrow and colleagues14 have shown
that measuring the antibody titre using
different cell lines and coronavirus types
produces markedly different antibody
levels.
In our studies at the Faculty of Veterinary
Science, University of Sydney (manuscript
in preparation), we measured the FCoV
type 1 antibody titres in 306 clinically
healthy cattery confined breeding cats
throughout NSW. Their antibody titres
ranged from zero to 1:102,400. Over two-
thirds of cats (213/306) had FCoV type 1
antibody titres of 1:1600 to 1:6400. This is
shocking to most cattery owners who are
used to the antibody titres reported by
Addie and colleagues that have an end
titre of 1:1280 and use FCoV type 2
infected cells in their indirect IFA method. If
cats are infected with FCoV type 1 and the
titre is measured with FCoV type 1 infected
cells, the titres reached may be
considerably higher than if measured
using another coronavirus.
While there is a very important role for
antibody titres in the management of
multicat households and the identification
of shedders, its use in the diagnosis of FIP in
individual cats is a dangerous exercise.
They can never be used alone to
determine a cat’s fate.
c) Fluid analysis and direct
immunofluorescence
The analysis of thoracic and abdominal
fluid is an essential diagnostic test in
effusive FIP. Microscopically, FIP effusion
typically consists of low numbers of
neutrophils and mononuclear cells
(macrophages). The presence of a high
protein effusion and low to moderate
number of cells as described above is
helpful in providing further evidence for
the likelihood of FIP, but has been found in
other disease processes.
Albumin/globulin ratios in serum and
effusion can be useful in the diagnosis of
FIP but are not specific for FIP, so must be
interpreted in light of all other evidence.
Serum albumin/globulin ratio <0.8 has a
high probability (92%) of FIP while an
effusion albumin/globulin ratio <0.4 also
has a high probability of FIP.
Techniques have been devised to detect
the presence of FCoV in macrophages
within the effusion. The method most
commonly used worldwide is direct
immunofluoresence. This technique uses a
fluorescein labelled anti-FCoV antibody to
detect large amounts of FCoV within
macrophages, an important differentiating
factor between FCoV based in the
intestines and mutant forms of FCoV.
Hartmann and colleagues found that
direct immunofluoresence was extremely
reliable at diagnosing FIP when positive
but can be unreliable when negative due
to the high rate of false negatives.22
Immunofluorescence is best done after
fluid analysis. In Australia it is available at
the Veterinary Diagnostic Pathology
Service (The University of Sydney) and
VETPATH® a private commercial lab in
Perth. The test relies on the macrophages
within the fluid being in good shape, so
delays in sampling lead to leakage of
FCoV from the macrophages and
increases the probability of a false
negative result. Tests are run daily in our
laboratory, with results available on the
same day the sample arrives to our
laboratory.

Figure 5: Direct immunofluorescence uses a
fluorescein labelled anti FCoV antibody to detect
large amounts of FCoV within macrophages
d) Histopathology + immunohistochemistry
The detection of characteristic
microscopic changes from biopsy samples
has been considered the only conclusive
test for FIP for a considerable time. Not all
cases of FIP have classical microscopic
appearance and this has led to the
development of more sensitive and
definitive diagnostic tests such as
immunohistochemistry.
Immunohistochemistry (IHC) is a sensitive
and specific technique used in many
infectious and neoplastic (cancer)
diseases. In the diagnosis of FIP we use an
antibody against FCoV to detect virus
within macrophages in formalin fixed tissue
sections (biopsy samples). It is used
subsequent to histopathology to
definitively confirm FIP in those cases when
the microscopic findings are inconclusive
or in some cases when the diagnosis must
be confirmed conclusively (eg for cat
breeders due to the implications in
breeding). This technique only detects
macrophages with sufficiently high
numbers of FCoV and allows the
macrophage to be view in context with
the surrounding pathology. Our laboratory
is currently the only one in Australia
offering this diagnostic test. All the external
laboratories in Australia routinely send
sections of the tissue to our laboratory for
testing and therefore can be requested on
any tissue sample through your usual
veterinary pathology service.
Management of FCoV and FIP in
breeding catteries
Confirming FIP as the definitive diagnosis
using histopathology +/-
immunohistochemistry is the essential first
step. Once FIP is confirmed, an analysis of
the breedline is required. Mapping the
pedigree of the affected cat and noting
any confirmed cases of FIP along the
family tree can be helpful. In several cases
it has been possible to identify a common
stud or queen that should be desexed and
removed from the breeding program.
Determining the Feline Coronavirus load of
individuals within the cattery is a useful
exercise if the information is used correctly.
Using RT-PCR to identify FCoV in the faeces
of cats, Diane Addie and colleagues in the
UK have determined that there are four
possible outcomes of exposure to FCoV
infection (www.dr-addie.com):
“1. The kitten or cat develops FIP (around
5- 10% of infections).
2. The vast majority of cats shed FCoV for a
while, develop antibodies, stop shedding
FCoV and their antibody titre returns to
zero. 58% of FCoV shedding lasts up to one
month and 95% of virus shedding lasts less
than 9 months.
3. The cat becomes a lifelong FCoV carrier
(13% of infected cats). These cats shed
FCoV continually in their faeces and most
remain perfectly healthy although some
develop chronic diarrhoea.
4. Resistant cats – around 4% of cats
appear to be completely resistant to FCoV
infection, they don’t shed the virus and
they mount an almost undetectable
antibody response. “
Their work24 also determined that a single
faecal RT-PCR result on its own is
meaningless because some cats may be
intermittent shedders of FCoV. RT-PCR
testing has to be part of a series of tests
and is best accompanied by
immunofluorescent antibody (IFA) testing
because RT-PCR can be prone to both
false positive results and false negative
results. Delays in getting the faeces sample
to the laboratory and at the incorrect
temperature causes destruction of the viral
RNA, leading to a false negative.
Establishing that a cat has eliminated
FCoV infection requires five consecutive
negative monthly RT-PCR results on faeces
OR a reduction in the FCoV antibody titre
(by indirect IFA) to less than 1:10. This may
take months to years to achieve in some
cases. These combined methods can be
useful in determining life long shedders of
FCoV. Removal of these cats from multicat
environments such as catteries is essential
for control of FCoV.
In Australia, RT-PCR is not currently
available however measurement of serum
antibody titres to FCoV using indirect IFA
can provide some helpful information. It is
accepted that the magnitude of the FCoV
antibody titre broadly reflects the viral load
within a given host.10, 11 Monitoring of these
values over time (every 6 to 12 months)
can provide information to the breeder
and veterinarian as to which cats are
chronic shedders and when the results are
examined for the whole cattery they can
be an indication of the success or failure of
husbandry changes. When measured
using indirect IFA with type 2 FCoV (Addie
et al), cats with low titres (1:25 or below)
are not shedding FCoV in their faeces.
Cats with high titres (1:400) are almost
always shedding high levels of virus. (NB In
Australia, FCoV type 1 testing is performed
and these give much higher readings, not
comparable with the above). Some of
these cats will stop shedding upon isolation
in a single cat household (detected by a
decrease in their titre). If the cat is
persistently shedding virus the titre will
remain high. Some catteries have attained
FCoV free catteries using these methods.
Screening for FCoV in any cat entering this
cattery is essential if the FCoV free status is
to be maintained.
Analysis of the husbandry practices of the
cattery (cleaning and number of litter
trays, use of disinfectants, cleaning and
management of food bowls etc) in the
cattery can lead to some helpful changes
in cattery management, which will assist in
reducing the faeco-oral cycling of enteric
based FCoV between cats. While it might
seem obvious to many, ensuring the food
bowls and litter trays are not cleaned in
the same area or with the same cleaning
instruments is essential. This has been an
issue in several catteries and rescue
agencies.
Recent studies by Addie and colleagues in
UK (unpublished; www.dr-addie.com)
have found that there is considerable
variation in the virus killing ability of kitty
litters. All the UK brands of kitty litter made
of Fuller’s earth were found to be much
more effective at killing FCoV than other
types, although these clumping litters have
risks associated with oral ingestion in
kittens. Further research in this area would
be useful. Using dedicated litter trays for
each cat or cat group, removing faeces
from litter trays as often as possible (1-2 x
daily) and using dedicated poop scoops
for each cat pen or tray is also
recommended.

Figure 6: Ensuring that food bowls and litter trays are
not cleaned in the same area is essential
Addie and Jarret have successfully
implemented early weaning protocols for
the prevention of FCoV infection in kittens
born in FCoV endemic catteries. This
involves isolating the queens 2 to 3 weeks
before parturition, strict quarantine of the
queen and her kittens in a separate room
from the rest of the cattery, and weaning
at 4 to 6 weeks of age. This protocol is
based on the finding that kittens are
protected from FCoV infection by their
maternal antibodies until 5-6 weeks of age,
when the maternal antibody wanes. The
maintenance of an isolated quarantine
area requires strict vigilance. Some find it
difficult to achieve and argue that the
early weaning has a social cost on the
kittens. Although a kitten may be
successfully raised free of FCoV it may
become infected later in life and therefore
the purpose of isolation and early weaning
is to delay the age at which FCoV
infection occurs.
Management of a cat in contact
with an FIP affected housemate
There is no current evidence to suggest
that a cat with FIP sheds the mutant virus in
his/her faeces. It is likely that the cats in the
household have been exposed to the
same enteric based FCoV depending on
their toileting habits in the household (ie
cats that defecate outside are thought to
be at lower risk of receiving the enteric
form of FCoV from their housemates).
Clients however will commonly present a
housemate of an FIP affected cat for
examination to determine its prognosis. It is
likely that this in-contact cat may have an
antibody titre to FCoV but this is in no way
predictive of its fate. If a high FCoV titre is
found the cat should be tested in 6 to12
months. Most cats in single or two cat
households will usually clear FCoV over a
few months to years. A persistently high
antibody titre does not necessarily indicate
a poor prognosis. Conversely, a
consistently low or negative titre is
indicative that the cat is highly unlikely to
develop FIP.
Treatment options
No therapies have been proved to
effectively treat FIP. Many
immunosuppressive (prednisolone,
cyclophosphamide, chlorambucil,
thalidomide) or immunomodulating drugs
(pentoxifylline) have been tried with
several providing temporary and often
short-term improvement.
One immunomodulating drug, feline
recombinant interferon omega (Virbagen
Omega®) has produced some
encouraging results25 when used with
prednisolone. The researchers used
1MU/kg s/c eod in combination with
glucocorticoid (prednisolone at 1mg/kg
bid or dexamethasone), to treat 12 cases
of FIP. Of the 12 cases, 4 cats were still
alive and well after 2 years, 4 cats survived
2 to 5 months while 4 cats survived less
than a month. Eleven of the 12 cats had
effusive disease. The age of the 4 cats who
were in remission at 2 years, ranged from 6
to 16 years and therefore were older. While
criticism of the criteria for FIP diagnosis has
been suggested by some, it remains the
only drug protocol with the potential to
limit the immune mediated tissue damage
and limit viral replication. The exact
mechanism by which this drug effects
changes in the cat’s immune response is
not understood at this time.
Use of this drug combination so far in our
hands has not met with overwhelming
success. We have had marked
improvement in clinical signs in two cats
(of 15) with confirmed FIP. Both have been
less than 3 years of age with pleural
effusion. One cat (a 9 month old Burmese
female desexed with effusive FIP (pleural
fluid)) had a noticeable response to
treatment with considerable reduction in
pleural fluid and clinical control of the
disease for 9 months before she had to be
euthanased due to deterioration of the
quality of life. The second cat (2.5 year old
male neutered Scottish Fold) with
noticeably improvement in clinical signs
and is currently going well (6 months since
diagnosis).
Katrin Hartmann and colleagues in
Germany have recently completed a
placebo controlled double blind clinical
trial. In this study to soon be published (late
2007 or early 2008), 37 cats with FIP were
treated randomly with feline interferon-ω
(106 IU/kg s.c. every 48 hours 7 days,
subsequently once every week) or
placebo. In all cats, FIP was confirmed by
histology or immunostaining of FCoV
antigen in effusion/tissue macrophages. All
cats received glucocorticoids, either as
dexamethasone (in case of effusion) or
prednisolone. They found that there was
no statistically significant difference in the
survival time of cats treated with
interferon-ω versus placebo. Cats survived
for a period of 3 to 200 days (mean 18
days). There was only one long-term
survivor (> 3 months) that appeared to be
in the interferon-ω group. This cat had
been presented with effusion that totally
disappeared; it did not show signs until
euthanized 200 days after treatment
initiation due to recurrence of FIP.
Although there was no difference in the
mean survival time, few cats may benefit
from treatment including interferon-ω.
Considerably more research is required to
understand the complex immune response
to FCoV and the development of FIP. With
this will come opportunities to develop
effective treatments or, even more
importantly, methods of preventing FIP.
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