Professional Documents
Culture Documents
Pathogenesis
Immunity
Most clinical signs are not directly caused by FIV,
Passive immunity so it is vital to check for the underlying cause
In natural infections, the efficacy of colostral
immunity is not known. Experimentally, of the presenting clinical signs.
susceptible kittens have been protected after
passive transfer of antibody in response to
challenge with laboratory-adapted isolates of
FIV.21 However, this may not apply to chal- Disease is often not seen until later in life –
lenge with virulent field strains, and indeed generally 4–6 years of age or older.
enhanced infection was seen after Immunodeficiency and/or
transfer of antibodies from cats immunostimulation most fre-
immunised with an experimental quently appear in the form
vaccine, indicating a fine balance of chronic gingivostomatitis,
between neutralising and infection- chronic rhinitis, lymphadeno-
enhancing antibodies.22 pathy, immune-mediated
glomerulonephritis and weight
Active immune response loss (Fig 2).
Cats infected with FIV remain Many concurrent viral, bac-
persistently infected despite terial, fungal and protozoal
mounting antibody and cell- infections have been reported
mediated immune responses. in FIV-infected cats.31,32
Feline immunodeficiency virus- Unusual or severe parasitic
a
specific CD8+ cytotoxic T cells are skin disease (eg, demodicosis,
detected in the blood within FIG 2 Infection with feline immunodeficiency virus may give pediculosis) or tumours should
1 week of infection.23 Coincident rise to chronic infections (a), and weight loss and haemorrhagic alert the clinician to the possi-
enteritis (b). Courtesy of (a) M L Van De Weerdt, Université de
with the peak of viraemia, anti- Liège; (b) Tadeusz Frymus
bility of FIV infection. Various
FIV antibodies, including virus neoplastic conditions, such as
neutralising antibodies, appear B cell lymphosarcomas, myelo-
in the plasma.24 They generally proliferative disease and squa-
appear from 2–4 weeks after mous cell carcinoma, have
infection, but seroconversion may been reported in association
be delayed in cats exposed to low with FIV infection.33
25
virus doses. Antibodies recog- Chronic gingivostomatitis is
nising Env appear earlier than one of the most common pre-
those against the Gag protein senting signs in FIV-infected
p24.26 cats, and impairs the cat’s qual-
ity of life (Fig 3).34
Clinical signs As confirmed by experimen-
tal infections with neurovirulent
Most clinical signs are not directly strains, central nervous system
caused by FIV, so it is vital to involvement and peripheral
check for the underlying cause of b neuropathy are early subclinical
the presenting clinical signs. In events, often associated only
many cases, clinical signs will be the result of with altered forebrain or peripheral nerve elec-
a secondary infection that should be identified trical activity.35,36 Behavioural changes, seizures,
and treated (see later). The virus itself is
responsible for immunodeficiency (making
the cat more susceptible to secondary infec-
tions and neoplasia) or immune stimulation
(resulting in immune-mediated disease). In
rare cases, FIV can cause neurological disease.
In the first weeks to months after infection,
clinical signs lasting for a few days to a few
weeks may be seen. These may include mild
fever, lethargy and peripheral lymphadenopa-
thy.27 Haematology may reveal a neutropenia.28
Infected cats then generally remain healthy a
before problems associated with immunodefi-
29
ciency develop; this asymptomatic period FIG 3 (a) Severe periodontal disease and
will last for years in most cases, and some cats (b) chronic gingivostomatitis are common signs in
cats with feline immunodeficiency virus infection.
30 b
will never develop FIV-related clinical signs. Courtesy of (a) Andy Sparkes; (b) Albert Lloret
disrupted sleep patterns, impaired learning and EBM ranking used in this article
paresis have also been reported.37
Reproductive failure occurs in infected cats Evidence-based medicine (EBM) is a process of clinical decision-making
and is associated with PCR-positive placental that allows clinicians to find, appraise and integrate the current best
and fetal tissues.38 Renal involvement arising evidence with individual clinical expertise, client wishes and patient needs
from glomerular and tubulointerstitial lesions (see Editorial on page 529 of this special issue, doi:10.1016/j.jfms.2009.05.001).
associated with severe proteinuria is frequent This article uses EBM ranking to grade the level of evidence of statements
in FIV-infected cats. Renal damage is caused in relevant sections on diagnosis, disease management and control as well
possibly by the virus, together with renal as vaccination. Statements are graded on a scale of I to IV as follows:
immune deposits.39 Polyclonal B cell activa- ✜ EBM grade I This is the best evidence, comprising data obtained from
tion sustains hyperglobulinaemia and high properly designed, randomised controlled clinical trials in the target
levels of circulating immune complexes and species (in this context cats);
autoantibodies.40,41 ✜ EBM grade II Data obtained from properly designed, randomised
controlled studies in the target species with spontaneous disease in
Diagnosis an experimental setting;
✜ EBM grade III Data based on non-randomised clinical trials, multiple
Direct detection methods case series, other experimental studies, and dramatic results from
✜ Virus isolation Virus isolation is a uncontrolled studies;
reliable diagnostic method but is laborious ✜ EBM grade IV Expert opinion, case reports, studies in other species,
and not used routinely. Peripheral blood pathophysiological justification. If no grade is specified, the EBM level
lymphocytes from fresh heparinised blood is grade IV.
samples are co-cultivated with primary
feline T cells for 2–3 weeks, and the Further reading
Roudebush P, Allen TA, Dodd CE, Novotny BJ. Application of evidence-based
presence of virus is confirmed by
medicine to veterinary clinical nutrition. J Am Vet Med Assoc 2004; 224: 1765–71.
measuring the levels of viral core proteins
in the culture fluids.
✜ Polymerase chain reaction Assays that
detect proviral DNA are available, but
vary in performance and may be inferior
to serological tests, with sensitivities and
specificities ranging from 40–100% and the transmembrane protein
[EBM grade I].42 Current PCR assays (communication from Idexx, March 2008).
detect clade A viruses well, but the other In contrast, immunochromatography tests
clades more variably. Strain variation may detect only antibodies recognising short
also explain discrepant results when peptides from the transmembrane protein.
identical samples are sent to different In Western blots, purified FIV is first
laboratories.43 separated by gel electrophoresis into its
constituent proteins, and the individual
Indirect detection methods FIV proteins are detected by antibodies.45
✜ Antibody detection Routine Both ELISA and immunochromatography
tests for FIV infection detect Discrepant PCR/serology results tests are generally appropriate,
As well as strain variation leading to discrepant
antibodies recognising viral but have limitations (see box on
results (see text), discrepancies may arise when
structural proteins (such as serology and PCR are compared: page 579).
the capsid protein p24 and a ✜ Seropositive/PCR negative results may be explained by ✜ CD4+ and CD8+ lymphocytes
gp41 peptide) and may take the presence of an FIV subtype not recognised by the PCR, It is possible to stage the level
the form of ELISA and rather than by the absence of FIV infection. This aspect is of immune dysfunction by
important if a cat has been vaccinated against FIV abroad.
immunochromatography ✜ Seronegative/PCR positive results may also be determining the CD4+ and CD8+
tests. Western blot analysis is found when cats living in close contact with FIV- lymphocyte counts. However, due
considered the ‘gold standard’ infected seropositive cats become provirus to the complexity of these assays,
for FIV serology and is used to positive without developing antibodies or and the fact that in a clinical
disease.44 Such cats are infected and
confirm inconclusive results. situation pre-infection values are
will usually seroconvert weeks to
In-house ELISAs are based on months later. not available, these tests are not
detecting antibodies recognising p24 clinically useful.
Shelters
Va c c i n a t i o n Feline immunodeficiency virus is an impor-
There is no FIV vaccine commercially available in Europe. Experimentally, tant consideration in rescue shelters as the
protection has been achieved by using several immunogens, including prevalence of infection is particularly high in
inactivated virus or infected cells, canarypox-based antigen expression in populations with a feral background and in
combination with inactivated cells and naked DNA.63 The most successful male cats. The prevalence may be lower in
so far have been whole inactivated virus preparations; one such vaccine pre-owned cats that have recently been relin-
has been on the market in the USA since 2002 quished, compared with sheltered stray cats.
and in Australia and New Zealand since 2004. The ABCD recommends that all cats should
However, this vaccine’s efficacy has not be tested. If this cannot be achieved, at least all
Not
been tested against challenge with recommended sick cats should be tested, and euthanasia con-
European field isolates and did not pro- The ABCD does not recommend sidered when the clinical problems relate to an
tect cats against a virulent UK primary
the use of the FIV vaccine in Europe, advanced stage of FIV infection.
because it invalidates the serological Serological tests do not reliably identify
FIV isolate [EBM grade III].64 Imported diagnosis of infections and may not
vaccinated cats might therefore not protect against European isolates.
infected kittens under 6 months of age. A pos-
be protected against naturally occur- itive result does not confirm that the kitten is
ring European isolates of FIV. infected and it must be emphasised that it is
not an indication for euthanasia. In this situa-
tion, diagnosis by PCR may be considered.
The ABCD recommends that in rescue shel-
ters, seropositive cats should be housed indi-
has been reported to prolong the survival vidually (unless from the same household);
times of FIV-infected cats [EBM III].62 as an absolute minimum, FIV-positive cats
should be segregated from FIV-negative cats.
Immune modulators and interferon inducers Some shelters will home FIV-positive healthy
Immune modulators and interferon inducers cats to selected adopters who offer living envi-
are widely used medications in FIV-infected ronments where the risk of infection for other
cats. There is no conclusive evidence from cats is minimal. Detailed counselling is
controlled studies that they have any benefi- required.
cial effects on health or survival. Rather, a
non-specific immune stimulation can lead to Breeding catteries
increased viral loads via the activation of Usually, cats in breeding catteries are kept
latently infected cells, and hence disease indoors and are tested annually, and hence FIV
progression. These products should not be is rare. New cats should be tested before being
used in FIV-infected cats. introduced, and breeders using an external stud
or allowing an external queen to visit their stud
Disease control in specific should request proof of FIV-negative status.
situations Cats that have escaped and returned should be
quarantined for 3 months, tested and returned
Multi-cat households to their group only if found to be seronegative.
The risk of FIV transmission is low in house-
holds with socially well-adapted cats. If one
cat is diagnosed with FIV infection, all cats in Acknowledgements
that household should be tested. The virus is
transmitted mainly during biting and fight- The European Advisory Board on Cat Diseases
ing, and if no aggression occurs due to the sta- (ABCD) is indebted to Dr Karin de Lange for
bility of social and territorial structures, the her judicious assistance in organising this
probability of transmission is low. In follow- special issue, her efforts at coordination, and
up studies, few additional cats seroconverted her friendly deadline-keeping. The tireless
over many years. All cats should be neutered, editorial assistance of Christina Espert-Sanchez
and no new cats introduced, as this might is gratefully acknowledged. The groundwork
disrupt the harmony, even between cats that for this series of guidelines would not have
have lived peacefully together for a long time. been possible without financial support from
If other infectious diseases are spreading in a Merial. The ABCD particularly appreciates the
multi-cat community, the risk of FIV transmis- support of Dr Jean-Christophe Thibault, who
sion may also be higher. In that situation, isola- respected the team’s insistence on scientific
tion of seropositive cats should be considered. independence.
KEY POINTS
✜ First isolated in 1986, feline immunodeficiency virus (FIV) is a retrovirus closely related to human immunodeficiency
virus. Most felids are susceptible to FIV, but humans are not.
✜ FIV is endemic in domestic cat populations worldwide (subtypes A and B are most common in Europe).
✜ Sick adult cats, male cats and free-roaming cats are most likely to be infected.
✜ FIV loses infectivity quickly outside the host and is susceptible to all disinfectants including common soap.
✜ Most FIV infections are acquired by bites (fights, mating) from persistently infected cats. The risk of transmission
is low in households with socially well-adapted cats.
✜ FIV infection has a long latent or ‘asymptomatic’ phase. Infected cats generally remain free of clinical signs for
several years, and some cats never develop disease.
✜ Most clinical signs are not caused by FIV, but are the consequence of immunodeficiency.
✜ Positive in-practice ELISA results obtained in a low-prevalence or low-risk population should always be confirmed
by a laboratory.
✜ PCR-based assays (for proviral DNA) are variable in performance and may even be inferior to serological tests.
✜ Kittens from FIV-infected queens may test seropositive due to persisting maternal antibodies, and should be
retested at 16 weeks of age.
✜ Cats should never be euthanased solely on the basis of an FIV-positive test result. FIV-infected cats may live
as long as uninfected cats.
✜ Asymptomatic FIV-infected cats should be neutered to avoid bite incidents and virus transmission.
✜ Surgery is well tolerated by asymptomatic FIV-infected cats, but perioperative antibiotic treatment should
be used in all cases.
✜ At present there is no FIV vaccine commercially available in Europe.
✜ Needles and surgical instruments used on FIV-positive cats may transmit the virus to other cats,
so strict hygiene is essential.
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