Download KeystepsTM Modular Medicine Session 1 Module 5

The 3 F’s
Rachel Dean BVMS DSAM(fel) MRCVS, Recognised RCVS specialist in feline medicine
Associate professor in Feline Medicine, Director of the Centre of Evidence Based
Veterinary Medicine,
School of Veterinary Medicine and Science,
University of Nottingham, Sutton Bonington Campus. Loughborough LE12 5RD
Tel: 0115 951 6575 Email: [email protected]
These notes are a comprehensive review of Feline infectious peritonitis, feline
immunodeficiency virus and feline leukaemia virus. The lecture will cover some of the
interesting aspects of these infections but will not cover everything in these notes!
Feline infectious peritonitis: A diagnostic dilemma
Feline infectious peritonitis is a fatal condition of predominantly young cats. There is
only limited understanding of the pathogenesis of this complex disease. The clinical
presentation of affected cats can vary significantly and reaching a diagnosis is not
straightforward. There is no single diagnostic test for FIP. Treatment of this disease is
supportive at best and it is invariably fatal.
The virus
FIP is caused by feline coronavirus (FCoV). Feline coronaviruses is one of the RNA
viruses which are very prone to mutation when they replicate hence multiple ‘strains’
exist. It is difficult to culture FCoVs in vitro, but there are two serotypes FCoV type I
which is feline only and FCoV type II which is genetically more similar to the canine
coronaviruses.
Most strains of FCoV will cause no clinical signs in infected cats, though mild transient
diarrhoea is sometimes seen. The diarrhoea may be more apparent if other enteric
pathogens are present
Two biotypes of FCoV are often referred to in the veterinary literature:
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1. Feline Enteric Coronavirus (FECV): the biotype that can’t leave the gut and
causes only a mild diarrhoea, and
2. Feline Infectious Peritonitis Virus (FIPV): a biotype that can leave the gut and
cause FIP.
However strains of FECV have been detected in the blood and it is now thought that any
strain of FCoV has the potential to cause FIP. This means wherever FCoV infection
exists so does the potential to develop FIP.
Transmission and Epidemiology
Infection with FCoV is endemic within the feline population as it is a highly contagious
virus. The prevalence of FCoV is thought to be approximately 40% in the general cat
population but this can rise to over 80% in pedigree and multicat households. However
the prevalence of FIP itself is still low, but accurate measures of incidence are not
available. It is thought by some that the prevalence of FIP may be increasing due to
alterations in cat husbandry leading to more indoor only, multicat households.
Spread of infection is primarily through ingestion of the virus via indirect transmission
from contact with faeces from infected cats. Direct transmission is possible via mutual
grooming, sharing of food bowls etc. The virus doesn’t persist well in environment but
can survive for up to 7 weeks in dried faeces.
Following initial infection with FCoV there is a definite primary stage where faecal
shedding of virus is high. Cats will then vary with shedding patterns and can
a) Stop shedding after a period of time, or
b) Become intermittent shedders at a low level, or
c) Persistently shed virus at a low level
Re-infection will FCoV mirrors primary infection with marked viral shedding after the
cat is infected. This variation in viral shedding is probably due to cat (immunological
factors), viral factors and environmental factors.
Pathogenesis
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The true pathogenesis of FIP remains unclear and involves a complex interaction of the
virus with cats’ the immune system. It is an immune-mediated disease involving the
virus, antibody and complement. The development of FIP depends on:
1) Viral factors – viral load, mutation
2) Cat factors – immune status, genetic predisposition
3) Environmental factors – the level of contamination of the environment with virus,
overcrowding etc
4)
Both cell mediated immunity and humoral immunity are involved in the protection from
FIP and clearance of FCoV infection. A cat can be immunocompromised due to
i) Illness
ii) Age – very young or very old
iii) Stress – multicat households, recent rehoming or surgery etc
iv) Genetic predisposition
This is potentially why almost 50% of FIP cases are seen in cats under the age of 2, and
why we see more FIP cases in multicat, pedigree and rescue environments.
To cause FIP, a multi-systemic disease, the FCoV has to leave the gut and become
systemic. The development of disease may be caused by
1) The virus infecting macrophages/monocytes, which then attach and cause damage
to blood vessels allowing the virus to enter tissues
2) The formation of immune complexes leading to the development of
pyogranulomas and organ damage.
The clinical signs and pathology of the disease are attributed to:
i) To the vasculitis and subsequent leakage of protein rich fluid from the damaged
vessels, and,
ii) Damage to organs due to vascular damage and pyogranuloma formation
This means multiple organs can be involved leading to the multitude of clinical signs.
Feline infectious peritonitis is therefore a misnomer and often leads to confusion for cat
owners. Feline infectious vasculitis would be a far more appropriate name.
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A case of FIP is most frequently an isolated event and this is because the development of
FIP occurs within the host. However sometimes ‘outbreaks’ of FIP are reported. Genetic
sequencing of the viruses involved in these ‘outbreaks’ show that different strains are
responsible for each case but they may originate from a ‘parent’ virus. These outbreaks
are more likely due to the cats being of similar genetic background and exposure to
common environmental factors which pre-dispose the cat to developing FIP.
The problem with FIP: Making an ante-mortem diagnosis of FIP is difficult. However
there are ‘clues’ in the signalment, clinical signs and diagnostic tests that can point you in
the right direction.
Signalment
There are clues in the history that may make the clinician suspicious of FIP, these
include:

Waxing and waning non-specific clinical signs

Young cat (peak incidence 2years old, smaller peak for cats over 13 years old)

Pedigree cat

Multicat household

Rescue cat at rehoming facility

Recent ‘stress’ – rehoming, neutering, vaccination, weaning
Clinical Signs
There is no clinical sign that is pathogonomic for FIP.
The clinical signs of FIP are often differentiated into effusive (‘wet’) and non-effusive
(‘dry’) FIP. In the authors opinion these presentation are just two extremes of the same
condition. If a patient with ‘dry’ FIP is monitored carefully and investigated fully, an
effusion is frequently identified. There is no doubt that cats with ‘wet’ FIP have
pyogranulomatous damage to organs as well as significant vasculitis leading to an
effusion.
Cats with FIP can present with various combinations of the following clinical signs:

Pyrexia, lethargy inappetance – the classic ‘sick’ cat!!
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
pyrexia

Abdominal effusion – this can be excessive and may cause vomiting, diarrhoea
and tachypnoea due to the size of the effusion

Dyspnoea, tachypnoea, muffled heart sounds –this is most commonly due to a
thoracic effusion, but pyogranulomas are frequently found throughout the lung
parenchyma.

Jaundice (see below)

Neurological signs – these can vary significantly, though signs of cerebellar
dysfunction are common in the author’s experience

Ocular is signs – photophobia, ocular pain, uveitis, iritis, keratic precipitates,
perivascular cuffing of the retinal vessels
A few tips:
Some cats with a marked abdominal effusion can initially be very bright and have a good
appetite.
A cat with neurological or ocular manifestations of FIP can vary significantly in severity
over time despite advancing disease and increased severity of pathology. This may be
erroneously attributed as a response to treatment
Diagnosis
At this point in time there is no single diagnostic test for FIP. Naming a diagnostic test an
FIP test is incorrect and misleading! Therefore it is imperative to be methodical and
thorough when investigating a cat for FIP – be vigilant for the ‘clues’!
Signalment
A good thorough case history is vital for obtaining some of the ‘clues’ associated with
FIP (see above)
Clinical examination:
The clinical signs of FIP can be varied and vague; hence a complete physical
examination is required. Some of the ocular and neurological manifestations can be
subtle. Repeat clinical examination is vital to monitor to progression of exiting clinical
signs or the development of further new clinical signs
I always include:
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
Routine physical examination – HR, PR, RR, BT, lymph node palpation etc

Complete ocular examination – including examination of the retina

Complete neurological examination – put the cat on the floor and watch it walk,
the signs of cerebellar dysfunction can be subtle

Careful abdominal palpation – a small abdominal effusion may give an abdomen
a stodgy feel. Some cats present with an abdominal mass, this may be enlarged
abdominal lymph nodes, some cats present with a thickened ileocaecocolic
junction (biopsy will demonstrate a pyogranulomatous enteritis).
Performing blood tests as part of an investigation of an FIP case is important, no
abnormality/ finding should be considered in isolation.
Haematology
The ‘clues’ include:

Lymphopenia

Non regenerative anaemia

Neutrophilia with left shift
Blood biochemistry
The ‘clues’ include

Hyperglobulinaemia –. This can be significant leading to albumen: globulin of
0.4. If serum protein electrophoresis is performed this can be demonstrated as a
polyclonal gammopathy.

Hyper bilirubinaemia – this is often in the absence of raised liver enzymes. The
author has also found increased fasting bile acids in a number of cases.

α1 alpha glycoprotein may be increased – this is an anti-inflammatory and
immunomodulatory agent in the body. This will also increase in other
inflammatory and neoplastic conditions
Imaging
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Both ultrasound and radiography can be helpful in identifying abdominal and thoracic
effusions and lymphadenopathies. Occasionally, using ultrasound, lesions can be
identified in the liver and kidneys but these are no specific for FIP.
Effusion analysis
The presence of an effusion will increase the suspicion of FIP, but again this is not
pathogonomic. Where possible it is important to try and obtain a sample of the fluid for
analysis – biochemistry, specific gravity and examination of the cells present in the
effusion should be performed. Differential diagnose such as heart disease, liver disease
and neoplasia should be considered.
The effusions caused by FIP can vary in appearance and in consistency. It may appear
chylous or haemorrhagic, and could be a modified transudate or an exudate
The classic effusion is:

straw coloured and clear

sticky – this is due to the protein content with globulins >35g/l and A:G <0.4

low cellularity – cells present will be mostly neutrophils and macrophages
The Rivalta test (put a drop of fluid into 98% ascetic acid – and watch for precipitation
due to high protein content) is easily performed. A negative test result would make FIP
unlikely.
Immunofluorescence can be performed on the fluid to try and identify FCoV in the
macrophages. A positive result is conclusive of FIP; however a negative result does not
rule it out. This test is further hampered by the low cellularity and therefore low levels of
macrophages often found in the effusions.
Serology
The presence of antibodies to FCoV IS NOT DIAGNOSTIC OF FIP. A positive FCoV
titre indicates that the cat has been exposed to FCoV. The majority of cats with FCoV
titres will NOT develop FIP, because the virus is so contagious most cats that are not
100% indoors will encounter the virus.
Make sure that you send all your samples to a good diagnostic laboratory with expertise
in feline infectious diseases.
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CSF analysis
In cats with neurological signs, obtaining CSF can be useful in supporting a diagnosis of
FIP. In general the CSF will have increased levels of protein and will show marked
pleocytosis. It is also worth testing for FCoV antibodies in the CSF as a positive result in
the presence of other findings will increase the suspicion of FIP.
Histopathology
This is considered to be the only definitive test for FIP as the pyogranulomas are very
characteristic. Unfortunately histopathology is often undertaken at post-mortem, but
biopsies taken ante-mortem should be considered. Immunofluorescence can be performed
on biopsy tissue to confirm FIP.
Treatment
Supportive and symptomatic treatment are both very important in cases of FIP. For
example raining large effusion, or administering fluids and NSAIDs can give cats’
transient relief.
More specific treatment with prednisolone and recombinant feline interferon ω have been
suggested as more specific therapy, but in the authors experience the positive effects of
these treatments are short lived.
Prevention and Control
Feline coronavirus is highly contagious and endemic in the UK cat population. This
means preventing infection is fraught with difficulty.
Simple hygiene procedures in multicat households and rescue facilities will significantly
reduce environmental contamination. For example:

reduce cat numbers – fewer cats, less virus

clean litter trays as soon as they are used

keep litter trays away from food bowls
Establishing a coronavirus free environment is difficult but has been tried in some
breeding households. A coronavirus-free cat is antibody negative and FCoV negative on
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faeces using PCR. To attempt to maintain a coronavirus free household the following
steps would have to be taken:

Initially blood test and faeces test all cats.

Separate positives and negatives and mange as two separate groups

Don’t mix cats until they have been faeces PCR negative for at least 3months

Early wean (age 5-6weeks) all kittens and maintain in isolation until 12-16weeks

Maintain a closed household
There is currently no FCoV vaccine available in the UK.
Feline Immunodeficiency Virus (FIV)
The virus
The feline immunodeficiency virus belongs to the lentivrius family, and is an RNA virus.
This means it requires an enzyme called reverse transcriptase (RT) to replicate. RT
facilitates the formation of proviral DNA which can be replicated so new virus can be
formed. Proviral DNA can also integrate with host DNA which can be permanent.
Various different subtypes (or clades) of FIV, that differ in their genetic make-up have
been identified. The different subtypes (A, B, C, D and E) have differing geographical
distribution between and within countries. Multiple subtypes have been isolated from
naturally infected FIV positive cats. The significance of the different subtypes should be
remembered when considering diagnosis and vaccination (see later).
FIV is similar to HIV, but it is though that FIV has existed in the population much longer
than HIV has in the human population. The similarities between HIV and FIV have
meant that FIV has been used experimentally in research aimed at developing HIV
treatments and an HIV vaccine. This has led to significant increases in the understanding
of the transmission, pathogenesis, treatment and prevention of FIV infection.
Epidemiology and transmission.
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FIV is common worldwide and there is a significant prevalence in the UK. The
prevalence varies depending on which cat population is being tested. There is no current
data on the prevalence of infection in the UK. It is thought that 3-4% of healthy cats will
be FIV positive, but this can increase in the sick cat population. The prevalence may be
as high as 20% in feral cats.
FIV does not survive well in the environment and readily killed by disinfectants, so
spread of infection is through direct cat to cat transmission. High levels of FIV are found
in both blood and saliva. Biting and fighting is thought to be the most common route of
transmission, hence there is a higher prevalence of FIV in entire male cats. FIV negative
cats that live in close contact with FIV positive cats tend not to become infected if there
is no fighting. It is unclear what the risk is for the negative cats in a multicat household
such as this.
Some but not all of the kittens born to an FIV positive queen will acquire infection in
utero or via the milk post-partum. Proviral DNA has been found in the tissues of neonates
in the absence of FIV antibodies in the blood, the significance of this is unclear. FIV has
also been isolated from semen and therefore, whilst rare, sexual transmission can also
occur.
Pathogenesis
The consequences of infection with FIV will depend on

The age of the cat at infection

The FIV isolate involved

The amount of virus

The route of infection

Whether the infection is with free virus or cell associated virus
Following infection, the virus is taken up by macrophages and lymphocytes, and
distributed to the lymphoid organs where it replicates. Virus is also distributed to organs
such as the kidney, central nervous system, bone marrow, lung and intestines. Viraemia
peaks a few weeks after infection and then falls as the body mounts an immune response.
Many antibodies to FIV are produced but these are ultimately ineffective at clearing
infection, but viral replication slows down and viraemia decreases. After the initial phase
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of infection there is a very gradual decline in immune function which is demonstrated by
a decrease in CD4+ lymphocytes. These are helper lymphocytes that are vital for
effective cell mediated and humoral immunity. The consequential immunosuppression
leads to chronic infection, chronic inflammatory conditions and neoplasia.
Clinical signs
Cats with FIV are presented at many different stages of infection.
They are occasionally presented during the early stages of infection and marked viraemia,
and may have the following non-specific signs:

Lymphadenopathy

Pyrexia

Lethargy

Inappetance.

Occasionally acute gastroenteritis, conjunctivitis, stomatitis and respiratory tract
disease is seen.
Frequently FIV infection is not suspected at this stage and often goes un-noticed by
owners.
Following initial infection cats will often be asymptomatic for years and will not be
presented for veterinary attention until the more chronic stages of infection. The clinical
signs are attributed to a chronic progressive immunosuppression and are due to:

Chronic opportunist infections – e.g. Demodex, Cryptosporidia, Toxoplasmosis,
Haemoplasma, Calicivirus, multiple fungi/bacteria

Chronic inflammatory conditions – e.g. stomatitis, rhinitis, uveitis conjunctivitis,
nephritis

Neoplasia (Cats with FIV are 5-10 times more likely to get neoplasia than FIV
negative cats)

Primary viral effects – e.g. pyrexia, lymphadeopathy, weight loss
The signs are chronic and recurrent.
Diagnosis of FIV
Most diagnostic tests are based around indentifying antibodies (as opposed to antigen in
FeLV testing) in the blood of persistently infected cats. Patient-side diagnostic tests and
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the screening tests used at commercial laboratories use enzyme linked immunosorbant
assays (ELISA) or rapid immunomigration (RIM) technology to detect antibodies to the
transmembrane envelope protein gp40, the core protein p24 or both.
Prior to performing a test for FIV it is important to establish

How likely is FIV infection?

How reliable is the test that you select? (sensitivity and specificity)

Are you using the test properly?
It is important to ensure that:
o The test is performed at the correct temperature
o That plasma/serum rather than whole blood is used (as specified in many test kits)
o The test is read at the correct time
This will reduce the number of tests that need to be repeated!!
A positive antibody result will be obtained when:
1. A persistently infected cat is tested
2. A kitten born to an FIV positive queen is tested, due to the transfer of maternally
derived antibodies. These antibodies can persist for up to 16 weeks, often longer –
so re-testing of kittens is advised at 6 months of age, or a text for antigen should
be used in young kittens.
3. It is a false positive!
4. (If the cat has received an FIV vaccine.)
A negative antibody result will be obtained when
1. A cat is not infected with FIV
2. In FIV infected cats where either the anti-FIV antibodies produced are not
detected by the test used or where no anti-FIV antibodies have been produced.
If it is in the very early stages of infection antibodies may not have been
produced yet, though up to 15% of FIV-infected cats never seroconvert,
remaining seronegative
3. It is a false negative!
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In most situations when a positive result is obtained this should be confirmed by a further
test. Commercial laboratories offer a range of tests which can be used to confirm a
positive including:
o Immunofluorescence
o Western blotting
o PCR
o Virus isolation (this can take up to 3 weeks!)
Always chose a laboratory that has expertise in feline infectious diseases and contact
them if an unusual result is obtained.
Note: Some laboratories offer PCR technology to confirm the presence of FIV infection.
Due to the genetic differences between clades (see notes above), some PCRs will not
identify all strains so false negatives can arise. PCRs are being developed to identify
more than one clade at a time in a single sample – this technique should overcome these
concerns
Management of FIV-infected cats
Chronically infected FIV cats can live for long periods of time with good symptomatic
and supportive therapy. Ideally an FIV positive cat should be assessed by a veterinary
surgeon at least once every 6 months to monitor for infections, neoplasia
Monitoring should include:
 Complete clinical examination, including ocular examination, and neuro
examination where appropriate
 Haematology – monitor for bone marrow suppression
 Biochemistry - monitor organ function, notably kidney function
 Urinalysis (including culture)
 Faecal analysis if clinical signs (including weight loss) attributable to the
intestinal tract are noted.
 FeLV antigen testing is also recommended as this can have a significant effect on
the prognosis and management of the case.
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Preventative medicine in the asymptomatic FIV-infected cat
(1) Vaccination - ideally with killed vaccines
(2) Routine flea and worm prevention
(3) High quality diet (avoiding raw milk or meat, and therefore the risk of opportunist
infection with Mycobacteria bovis and Toxoplasma gondii)
(4) Dental care and oral hygiene is recommended as many FIV-infected cats suffer
from chronic gingivostomatitis.
(5) Keep the cat indoors: to reduce spread of the disease and minimise exposure of
the immunocompromised patient to other infectious agents.
(6) Neuter any entire FIV positive cats
(7) Reduce stress where possible
It is important to emphasise to owners the role that they play in caring for an FIV positive
cat. Without a dedicated owner successful management will be limited.
In an ideal world if the owner of an FIV positive cat has more than one cat, the cats
should be housed separately or rehomed. If there is no conflict in the house the risk of
spread of infection is low but not zero! If the owner is reluctant to separate the cats then
the use separate feeding bowls to minimise the risk of transmission of virus via saliva is
recommended.
If an FIV positive cat becomes sick it is important to emphasise to the owner that they
must seek veterinary treatment very promptly. It is thought that 80% of clinical signs in
FIV-infected cats are related to immunosuppression and resultant secondary infection.
Many of the conditions can be overcome if treated promptly and aggressively, for
example:

Anaemia due to Mycoplasma haemofelis can be successfully treated with
antibiotics

Gingivitis is a common finding in FIV infected (and non-FIV infected!) cats.
Regular dental check-ups and treatment accompanied by oral hygiene will
potentially reduce the severity and frequency of the recurrence.
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
Pyrexic, leucopenic cats should be treated with broad spectrum antibiotics as soon
as possible.

Neoplasia in FIV positive cats can still be treated and it is thought that they can
respond as well as an FIV negative cat initially, though the long term prognosis is
poor.

Chronic anaemia is often seen in the latter stages of FIV, erythropoietin will help
alleviate some of the associated clinical signs. Prolonged usage will lead to the
development of antibodies to the EPO so the treatment will be rendered
ineffective
Specific antiviral treatment
Many drugs have been used against FIV in vitro with a view to treating HIV in man,
hence many of them are either toxic to cats, not formulated in a practical ‘cat’ size or are
prohibitively expensive!. There is very little evidence in the veterinary literature
regarding the use of anti-virals in naturally infected cats. Hence we are still limited with
FIV specific therapy.
AZT is the most commonly used specific anti-viral drug used in FIV positive cats. It is a
reverse transcriptase inhibitor that works because they are nucleoside analogues which
compete with cellular nucleotides that are the building blocks for proviral DNA – hence
these drugs inhibit viral replication. This drug has been shown to improve the clinical
signs and laboratory parameters in some FIV cats. It is often recommended for FIV cats
with chronic gingivostomatitis that has been unresponsive to all other therapy. AZT can
be used orally or subcutaneously at a dose of 5mg/kg 2-3 times daily. Anaemia can be
seen as a side-effect of AZT so should not be used in cats that already have low red blood
cell counts. The anaemia is usually reversible and only seen at doses of up to
15mg/kg/day. Haematology should therefore be regularly assessed throughout therapy.
Eventually the virus would become resistant to RT inhibitors, this combined with the
potential side-effects means these drugs are often only used as a ‘last resort’.
Recombinant feline omega interferon (virbagen omega) is now licensed for use in FIV
(and FeLV) positive cats during the non-terminal stages of infection. The effects and
application of this drug in retrovirus positive cats has not been fully assessed.
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Evening primrose oil, has been suggested to have beneficial effects such as increased
body weight, haematocrit and neutrophil count have been reported. The recommended
dose rate of one 550mg capsule daily
Prevention
Fort Dodge have developed an FIV vaccine – Fel-O-Vax FIV, which is licensed in the
USA and Japan. As the vaccine effectively induces a protective antibody response,
general use in the cat population would make it impossible to interpret antibody test
results. A vaccinated cat would give the same result as an infected cat. Not all clades are
included in the vaccine, so accurate information about the prevalence of clades in the UK
and many parts of Europe and evidence demonstrating cross-protection is required.
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Feline Leukaemia Virus (FeLV) Infection
The virus
Feline leukaemia virus, like FIV is a single-stranded RNA virus belonging to the
retrovirus family. To divide retroviruses require the enzyme reverse transcriptase (RT)
that enables genomic RNA to be transcribed to proviral DNA. This proviral DNA is then
incorporated into the host DNA of the infected cell, which means that all subsequent
daughter cells will also be ‘infected’ with proviral DNA.
Endogenous retrovirus DNA is found within the feline genome. This DNA material will
not produce viral particles, but becomes important when a cat meets an exogenous
retrovirus (see below).
FeLV is divided into 3 subgroups based on differences in the envelope protein gp70:
1. Subgroup FeLV-A. This is the form of the virus which is infectious from cat to
cat, it is low pathogenicity but highly contagious.
2. Subgroup FeLV-B. This subgroup arises within an individual cat from
combinations of FeLV-A and endogenous retrovirus DNA. FeLV-A is also
required to facilitate replication of FeLV-B. FeLV-B is not contagious. It is found
with FeLV-A in approximately 50% of cats who have neoplasia due to FeLV.
3. Subgroup FeLV-C. This subgroup is also non-contagious and arises within the cat
after genomic and FeLV-A DNA combine. It is much rarer than the other
subgroups and is associated with non-regenerative anaemias.
Epidemiology and transmission
The true prevalence of FeLV in the UK is unknown. However it is widely agreed that the
prevalence of infection has decreased since the introduction of FeLV vaccination and
active ‘test and remove’ programmes. It is thought that the prevalence may be 1% in
health cats and up to 12% in sick cats. Some studies have shown a much higher
prevalence (up to 20%) in sick cats. In contrast to FIV, FeLV is of higher prevalence in
‘friendly’ or ‘social’ cats as prolonged contact is needed for transmission (see below).
Hence FeLV is seen equally in males and females, and is more common in younger cats.
FeLV is transmitted via close cat to cat contact, mostly through saliva and nasal
secretions. In viraemic cats the level of virus in saliva is many times higher than in blood.
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The level of virus shedding through saliva is the same whether the cat is sick or healthy.
Infection is spread through social activities such as mutual grooming and sharing food
bowls. The virus does not survive well in the environment and is easily killed by
disinfectant.
FeLV infected pregnant queens can vertically transmit infection to their offspring through
grooming, in utero and through milk. Most FeLV positive queens are infertile, and if any
kittens are born they are highly likely to be permanently infected.
Kittens are more susceptible to infection with FeLV than adult cats, and the majority of
cats with FeLV related illness will be less than 6 years of age. However older cats can
still become permanently infected with FeLV and succumb to FeLV related diseases
Pathogenesis
Following infection via the oronasal route, the virus replicates in the lymphoid tissue of
the oropharynx. There are 4 main outcomes to infection:
1. Recovery: In many cats an effective immune response is mounted and infection
never becomes systemic. These cats will often have anti-FeLV antibodies and will
have good protection from infection for a number of years
2. Transient viraemia: If an adequate immune response is not mounted, then FeLV
will spread systemically via lymphocytes and monocytes. If this period of
viraemia is short-lived and is stopped before the bone marrow is infected, then the
cat will recover and be protected from further infection. This transient viraemia
and viral shedding lasts approximately 3-6 weeks (maximum 16weeks), cats will
be positive for viral antigen during this viraemic period.
If the viraemia persists and the bone marrow is infected, whilst a small proportion of
cats can still clear infection, the majority go on to be either persistently or latently
infected.
3. Latent infection: Cats that are latently infected have FeLV DNA in the cells of the
bone marrow but will not be viraemic so will be negative on routine antigen
testing. The latency can be reactivated (spontaneously or in times of stress e.g.
lactation) and the cat becomes viraemic and sheds virus once more (and becomes
positive on antigen testing). Cats with a latent infection may intermittently
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relapse, recover or eventually develop a persistent viraemia and die due to FeLV
related disease.
4. Persistent viraemia: Following transient viraemia or latent infection FeLV cats
can become persistently viraemic and shed high levels of virus. Within 3 years
80% of these cats will develop FeLV related disease and die.
Clinical signs
The majority of cats present with clinical signs of FeLV due to:

Anaemia

Immunosuppression, or

Neoplasia
Anaemia
The anaemia associated with FeLV can be regenerative or non-regenerative
Regenerative anaemia can be a consequence of:

Immune mediate haemolytic anaemia

Thrombocytopenia

Haemoplasma infection
Non-regenerative anaemia can be a consequence of

Pancytopenia – due to direct viral effects on all cell lines in the bone marrow

Pure red cell aplasia – due to direct viral effects selective for red cell precursors in
the bone marrow

Anaemia of chronic disease- e.g. neoplasia, chronic inflammatory conditions

Leukaemia – Myeloid or lymphoid

Myelopthesis/myelofibrosis

Lymphoma of the bone marrow
Immunosuppression
FeLV has a more debilitating effect on the immune system than FIV. The mechanisms by
which FeLV causes immunosuppression are poorly understood, but the virus has
profound effects on both cell mediated and humoral immunity. The consequences are
chronic, debilitating bacterial, fungal and viral infections
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Neoplasia
Various different tumours have been attributed to FeLV infection, and the presence of
FeLV markedly increases a cat’s risk of neoplastic disease. The most common are:
o Lymphoma – Mediastinal, alimentary, multicentric, extranodal (e.g. renal, spinal,
ocular)
o Leukaemia – Lymphoid or myeloid
o Other solid tumours – fibrosarcomas, osteochondromas
The clinical signs associated with FeLV infection are therefore varied and numerous. The
presenting clinical signs will depend on the organ systems affected, and commonly
include:
 Lymphadenopathy – reactive or neoplastic
 Gastrointestinal – vomiting, diarrhoea, weight loss
 Respiratory – altered respiratory rate and pattern due to mediastinal, pleural,
parenchymal and upper respiratory tract infection or neoplasia
 Ocular – uveitis/conjunctivitis due to secondary infection, chronic inflammation,
or neoplasia
 Neurological – signs referable to the central and peripheral nervous system can be
present due to infectious, inflammatory or neoplastic conditions
 Urinary – e.g. enomegaly (most commonly due to lymphoma), neurological
dysfunction of the lower urinary tract
 Reproductive failure
Diagnosis of FeLV infection
There are patient side tests available to aid the diagnosis of FeLV. These identify the viral
antigen p27 most commonly by ELISA or RIM methods. The majority of these test have
high sensitivity (nearly 100%) so false negatives are rare. However as the prevalence of
infection is very low in healthy cats and specificity is around 98%,
A positive patient side test should ALWAYS be confirmed by a second test.
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The positive predictive value is much more reliable in sick cats where the prevalence of
infection is higher.
When testing for FeLV remember,
1. FeLV vaccines do not interfere with testing as we are looking for antigen not
antibody (many vaccinated cats will not have antibodies either but are protected)
2. A positive test result does not tell you if a cat is permanently or transiently
infected. Re-testing 12 weeks later or delaying testing until 12 weeks after known
exposure will help differentiate the two.
3. Any cat that is viraemic is potentially shedding virus and can infect other cats
4. If a cat has a non-regenerative anaemia or a tumour that we commonly encounter
in FeLV infection but is antigen negative, then confirmatory tests are
recommended.
5. A cat with latent infection can still be antigen negative yet harbour infection, and
may be viraemic at a later date. (see discordant results)
(It is important to ensure that the patient side tests are carried out in line with the
manufacturer’s instructions to improve accuracy – see FIV notes)
Confirmatory tests
Virus Isolation – this is currently the most commonly employed confirmatory test for
FeLV infection in the UK.
Immunofluorescence – this is commonly used in the USA and identifies virus within
white blood cells
Polymerase Chain Reaction – PCRs have now been developed to detect exogenous FeLV
infection, and are very sensitive (see below). They are not yet commonly used in
diagnostic laboratories
Discordant results
There are a number of cats that will test positive on routine screening tests (ELISA and
RIM) but will be negative on virus isolation or Immunofluorescence.
A discordant result means circulating antigen is detectable but virus isn’t.
Approximately 10% of all positive results are discordant, though in some studies this
reached 40%!
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Variations in test sensitivity, latent and localised infections may account for some of the
discordant results – but not all of them. The concerns are:

Are cats with discordant results infectious?

Are they likely to succumb to FeLV related disease?
These questions largely remain unanswered, but it is thought most persistently discordant
cats should be considered false positives.
Interestingly some cats that are antigen positive by are negative on confirmatory tests are
proviral DNA positive on PCR. In fact some cats that are negative on all other tests can
be positive on PCR – the significance of these results is unclear. It has been suggested
that all cats that meet FeLV may incorporate proviral DNA, but they will not necessarily
be viraemic or infectious. Further work needs to be done to clarify this situation and
follow cats that are PCR positive but not antigenaemic or viramic..
Haematology in FeLV infected cats.

Various abnormalities of all cell lines can be found in FeLV positive cats.

The author advises sending the sample away to a reputable commercial laboratory
for analysis and blood smear examination by an experienced veterinary
haematologist

FeLV testing is recommended in any ‘at risk’ cat with severe or multiple
abnormalities on blood smear examination.

FeLV positive anaemic cats can demonstrate macrocyctosis, even when the
anaemia is non–regenerative.

Immature forms (e.g. erythroblasts, lymphoblasts) of all cells lines can be found
in circulation in cats with FeLV infections of the bone marrow
Treatment
All FeLV positive cats should be separated from FeLV negative cats
(a) Healthy FeLV-infected cats
A positive result in a healthy cat should mean that a confirmatory test is performed and
the cat re-tested in 12 weeks. The majority of cats will only be transiently infected. The
true healthy FeLV positive cat will succumb to disease at some point. Regular health
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screening as suggested for FIV cats is recommended for FeLV positive cats. A very poor
prognosis should be given
(b) Sick cats infected with FeLV
Cats with disease due to FeLV have a very guarded prognosis. Aggressive rapid
treatment of opportunist infections and chronic inflammatory conditions is recommended
(see FIV notes). Lymphoma due to FeLV infection will still respond to chemotherapy and
other treatment modalities but the long term prognosis is poor.
Control
FeLV does not survive well outside the cat; therefore fomites and environmental
contamination do not pose a threat to a naive cat.
If a FeLV positive cat is housed in isolation with no missing of food bowls, grooming
equipment etc, spread of infection is unlikely.
Endemic infection in catteries and breeding establishments is thankfully much less
common than it used to be. The ‘test and remove’ management scheme of a problem
household, where all positive cats are removed, isolated and re-tested 12 weeks later
will successfully eliminate infection from a multicat household
There are many FeLV vaccines currently on the market that almost all demonstrate
good protection from persistent infection. FeLV vaccines do not prevent transient
viraemia but are important in the control of FeLV in cat populations.
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