Abstract
Feline
leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are among the
most common infectious diseases of cats. Although vaccines are available for
both viruses, identification and segregation of infected cats form the
cornerstone for preventing new infections. Guidelines in this report have been
developed for diagnosis, prevention, treatment, and management of FeLV and FIV
infections. All cats should be tested for FeLV and FIV infections at
appropriate intervals based on individual risk assessments. This includes
testing at the time of acquisition, following exposure to an infected cat or a
cat of unknown infection status, prior to vaccination against FeLV or FIV,
prior to entering group housing, and when cats become sick. No test is 100%
accurate at all times under all conditions; results should be interpreted along
with the patient's health and risk factors. Retroviral tests can diagnose only
infection, not clinical disease, and cats infected with FeLV or FIV may live
for many years. A decision for euthanasia should never be based solely on
whether or not the cat is infected. Vaccination against FeLV is highly
recommended in kittens. In adult cats, antiretroviral vaccines are considered
non-core and should be administered only if a risk assessment indicates they
are appropriate. Few large controlled studies have been performed using
antiviral or immunomodulating drugs for the treatment of naturally infected
cats. More research is needed to identify best practices to improve long-term
outcomes following retroviral infections in cats.
Epidemiology
Feline leukemia virus (FeLV) and feline
immunodeficiency virus (FIV) are among the most common infectious diseases of
cats. In the United States, prevalence of both infections is less than 2% of
healthy cats and is between 6 and 33% of high-risk cats and cats that are
tested during illness (O'Connor
et al 1991, Moore
et al 2004, Levy et
al 2006b). Risk factors for infection include male gender,
adulthood, and outdoor access, whereas indoor lifestyle and sterilization are
associated with reduced infection rates (Hoover
and Mullins 1991, O'Connor
et al 1991, Levy
2000, Levy
and Crawford 2005, Levy et
al 2006b).
The prevalence of FeLV infection has reportedly decreased
during the past 20 years, presumably as a result of implementation of
widespread testing programs and development of effective vaccines (O'Connor
et al 1991, Moore
et al 2004, Levy et
al 2006b). In contrast, the prevalence of FIV has not changed
since the virus was discovered in 1986. Testing for FIV infection is less
common, and a vaccine against FIV was not introduced until 2002. Whether the
prevalence of FIV infection will change in the future is unknown.
In a study of more than 18,000 cats tested in 2004,
2.3% were positive for FeLV and 2.5% were positive for FIV (Levy et
al 2006b). For both viruses, prevalence was higher among cats
tested at veterinary clinics (FeLV 2.9% and FIV 3.1%) than among cats tested at
animal shelters (FeLV 1.5% and FIV 1.7%) and among pet cats that were allowed
outdoors (FeLV 3.6% and FIV 4.3%) than among pet cats that were kept strictly
indoors (FeLV 1.5% and FIV 0.9%). Infections were higher among sick cats than
healthy cats and were highest among sick feral cats (FeLV 15.2% and FIV 18.2%)
followed by sick pet cats allowed access to the outdoors (FeLV 7.3% and FIV
8.0%). In contrast, positivity in healthy feral cats (FeLV 1.0% and FIV 3.3%)
was less common or similar that in to healthy outdoor pet cats (FeLV 2.6% and
FIV 3.2%).
Although infected cats may experience a prolonged
period of clinical latency, a variety of disease conditions are associated with
retroviral infections, including anemia, lymphoma, chronic inflammatory
conditions, and susceptibility to secondary and opportunistic infections (Hoover
and Mullins 1991, Levy
2000). Specific disease syndromes are associated with a
very high prevalence of retroviral infections, such as cutaneous abscesses
(FeLV 8.8% and FIV 12.7%) (Goldkamp
et al 2008) and oral inflammation (FeLV 7.3% and FIV 7.9%)
(Bellows, unpublished data).
Identification
and segregation of infected cats is considered to be the single most effective
method for preventing new infections with FeLV and FIV. Despite the
availability of point-of-care testing for FeLV and FIV infections and of FeLV
and FIV vaccines, less than one quarter of all cats have ever been tested, and
infections with these viruses are still common. Although characteristics such
as gender, age, lifestyle, and health status can be used to assess the likely
risk of FeLV and FIV infections, most cats have some degree of infection risk.
While
FeLV and FIV can be life-threatening viruses, proper management and treatment
can give infected cats longer, healthier lives. The following guide reflects
the recommendations of the American Association of Feline Practitioners (AAFP)
on managing these infections.
Pathogenesis
FeLV
pathogenesis
FeLV is commonly spread vertically from infected
queens to their kittens and horizontally among cats that live together or that
fight. The susceptibility of cats to FeLV is believed to be age dependent, but
the degree of natural resistance is unknown. In one study, all newborn kittens
and the majority of cats up to 2 months of age experimentally infected with
FeLV developed progressive FeLV infection, but only 15% of cats inoculated when
they were 4 months or older became infected (Hoover
et al 1976). More recent studies, however, have demonstrated
efficient natural and experimental infection of adult cats (Grant
et al 1980, Lehmann
et al 1991).
FeLV pathogenesis has been studied for decades using
virus culture, immunofluorescent antibody (IFA) assays, and antigen detection (Hoover
et al 1975,Hardy
et al 1976a, Pedersen
et al 1977, Rojko
et al 1979, Lutz et
al 1980, 1983,Hoover
and Mullins 1991, Rojko
and Kociba 1991). In most cats, antigenemia (presence of viral
proteins in the blood) correlates with viremia (presence of infectious virus
that can be cultured from the blood), although a few cats have circulating
virus without detectable antigens or antigens without viremia (Jarrett
et al 1982). Cats typically acquire FeLV via the oronasal route
by mutual grooming but can also acquire the virus through bites. Viremic cats
shed infectious virus in multiple body fluids, including saliva, nasal
secretions, feces, milk, and urine (Hardy
et al 1976b, Pacitti
et al 1986). After virus exposure, FeLV can be found first in
the local lymphoid tissues; it then spreads via monocytes and lymphocytes into
the periphery (Rojko
et al 1979).
The outcome of infection with FeLV is currently
controversial. In the past, approximately one third of cats were believed to
become persistently viremic and up to two thirds to eventually clear the
infection (Hoover and Mullins 1991). Newer
research suggests that most cats remain infected for life following exposure
but may revert to an aviremic state (regressive infection) in which no antigen
or culturable virus is present in the blood but in which FeLV proviral DNA can
be detected in the blood by polymerase chain reaction (PCR) (Hofmann-Lehmann
et al 2001, Torres
et al 2005, Pepin
et al 2007). The clinical relevance of PCR-positive,
antigen-negative cats is not yet clear. The provirus is integrated into the
cat's genome, so it is unlikely to be cleared over time (Cattori
et al 2006). Although these cats are unlikely to shed infectious
virus in saliva, proviral DNA might be infectious via blood transfusion (Chen et
al 1998). The continuous presence of provirus might explain
the long persistence of virus-neutralizing antibodies in ‘recovered’ cats.
Prior to the development of PCR, a status of ‘latent’ infection was described
in which the absence of antigenemia was accompanied by persistence of
culturable virus in bone marrow or other tissues but not in blood (Post
and Warren 1980, Rojko
et al 1982, Madewell
and Jarrett 1983, Pedersen
et al 1984,Pacitti
and Jarrett 1985, Hofmann-Lehmann
et al 2007). The ‘latent’ infection may be a phase through which
cats pass during regressive infection (Boretti
et al 2004).
FeLV provirus (DNA) and plasma viral RNA are usually
detectable by PCR within 1 week of FeLV exposure, even if FeLV antigen is not.
All cats with progressive and regressive infection seem to undergo this phase
and to develop similar proviral and plasma viral RNA loads in the peripheral
blood during early infection (Hofmann-Lehmann
et al 2008). Following FeLV exposure, FeLV infection has four
possible outcomes (Torres
et al 2005, Hofmann-Lehmann
et al 2007, 2008).
In cats with progressive infection, FeLV infection is
not contained during early infection, and extensive virus replication occurs
first in the lymphoid tissues and then in the bone marrow and in mucosal and
glandular epithelial tissues in most infected cats (Rojko
et al 1979). Mucosal and glandular infection is associated with
excretion of infectious virus in cats with progressive infection. Progressive
infection is characterized by insufficient FeLV-specific immunity, and cats
frequently succumb to FeLV-associated diseases within a few years.
Regressive infection is accompanied by an effective
immune response, and virus replication is contained prior to or at the time of
bone marrow infection. Cats with regressive infection are at little risk of
developing FeLV-associated diseases. FeLV is integrated into the cat's genome,
but viral shedding does not occur (Pedersen
et al 1977, Lutz et
al 1983, Flynn
et al 2000, 2002).
Following infection, regressive and progressive
infections can be distinguished by repeated testing for viral antigen in
peripheral blood (Torres
et al 2005). Most infected cats initially become antigen
positive within 2–3 weeks after virus exposure. They may then test negative for
viral antigen 2–8 weeks later or, in rare cases, even after many months
(regressive infection). Both progressive and regressive infections are almost
always accompanied by persistent FeLV proviral DNA in blood. Some infected cats
never develop detectable antigenemia. In this case, real-time PCR is more
sensitive than antigen detection to detect FeLV exposure.
Abortive exposure has been observed infrequently
following experimental FeLV inoculation and is characterized by negative test
results for culturable virus, antigen, viral RNA, and proviral DNA after FeLV
exposure (Torres et al 2005, 2006).
Focal infections have been reported in early studies.
They are rare and occur in cats with FeLV infection restricted to certain
tissues, such as the spleen, lymph nodes, small intestine, or mammary glands (Pacitti
et al 1986, Hayes
et al 1989).
View
this table:
Table 1
Outcomes of FeLV
infection
FIV Pathogenesis
FIV is shed in high concentrations in the saliva,
which also contains infected leukocytes. The major mode of transmission is via
bite wounds. Transmission of FIV from infected queens to their kittens has been
reported in laboratory-reared cats (O'Neil
et al 1995, Allison
and Hoover 2003), but this appears to be an uncommon event in nature
(Ueland and Nesse 1992, Pu et
al 1995). Although transmission among household cats that do
not fight is uncommon, it is still possible. In one household of 26 cats that
were not observed to fight, FIV infection was originally diagnosed in nine
cats, but spread to six other cats during a 10-year observation period (O'Neil
et al 1995,Addie
et al 2000). Sexual transmission, the most common mode of
transmission of human immunodeficiency virus (HIV), appears to be unusual in
FIV, even though the semen of infected cats frequently contains infectious
virus (Jordan et al 1998).
Acute FIV infection is associated with transient
fever, lymphadenopathy, and leukopenia but frequently goes unnoticed by cat
owners. Virus is detected in high concentrations in the blood by culture and
PCR within 2 weeks of infection. Within the first few weeks of FIV infection,
both CD4+ (helper) and CD8+ (cytotoxic-suppressor) T-lymphocytes decline (Egberink
and Horzinek 1992, Yamamoto
et al 2007). The initial lymphopenia is followed by a robust
immune response characterized by the production of FIV antibodies, suppression
of circulating viral load, and a rebound in CD8+ T-lymphocytes in excess of
preinfection levels. This results in inversion of the CD4+:CD8+ T-lymphocyte
ratio that is likely to persist for the rest of the cat's life. Over time, both
CD4+ and CD8+ T-lymphocytes gradually decline. The immune response is unable to
eliminate infection, and the cat remains infected for life.
Following the primary illness, cats enter a prolonged
asymptomatic period that may last for years. During this time, progressive
dysfunction of the immune system occurs. Although chronic inflammatory
conditions and opportunistic infections are more common in cats with low CD4+
T-lymphocyte counts, some cats with severe CD4+ T-lymphocytopenia remain
healthy. That cell-mediated immunity is more profoundly affected than humoral
immunity is generally recognized. Chronic inflammatory conditions, neoplasia,
and infections with intracellular organisms, therefore, are more common than
infections controlled by antibodies in FIV-infected cats. FIV-infected cats
also appear to respond adequately to vaccination. Polyclonal hyperglobulinemia
characteristic of non-specific stimulation of humoral immunity is common in
cats with chronic FIV infection. In human HIV infections, distinctive clinical
stages can be defined based on absolute CD4+ T-lymphocyte counts and plasma
viral RNA load. Similar systems have been attempted for staging FIV infections
but are not as clearly defined (Walker
et al 1996, Goto et
al 2002).
Diagnosis of FeLV and FIV
The
retroviral status of all cats should be known because the serious health
consequences of infection influence patient management both in illness and
wellness care. Accurate diagnosis of infection is important for both uninfected
and infected cats. Identification and segregation of infected cats is
considered to be the most effective method for preventing new infections in
other cats. Failure to identify infected cats may lead to inadvertent exposure
and transmission to uninfected cats. Misdiagnosis of infection in uninfected
cats may lead to inappropriate changes in lifestyle or even euthanasia.
Cats
may require retrovirus testing at different times in their lives. For example,
cats that meet the following criteria should be tested for FeLV and FIV
infections:
·
Sick cats should be tested even if they have tested
negative in the past.
·
Cats and kittens should be tested when they are first
acquired.
o ○ Even
cats that are not expected to live with other cats should be tested for several
reasons, including the impact on their health, the possibility of other cats
joining the household, and the possibility that cats confined indoors may
escape and be exposed to other cats.
o ○ Tests
should be performed at adoption, and negative cats should be retested a minimum
of 60 days later.
·
Cats with known recent exposure to a
retrovirus-infected cat or to a cat with unknown status, particularly via a
bite wound, should be tested regardless of previous test results.
o ○ Testing
should be carried out immediately and, if negative, should be repeated after a
minimum of 30 days for FeLV and after a minimum of 60 days for FIV. When the
type of possible viral exposure is unknown, retesting for both viruses after 60
days is most practical.
·
Cats living in households with other cats infected
with FeLV or FIV should be tested on an annual basis unless they are isolated.
·
Cats with high-risk lifestyles (eg, cats that have
access to the outdoors in cat-dense neighborhoods and cats with evidence of
fighting such as bite wounds and abscesses) should be tested on a regular
basis.
·
Cats should be tested before initial vaccination
against FeLV or FIV.
·
Cats used for blood or tissue donation should have
negative screening tests for FeLV and FIV in addition to negative real-time PCR
test results.
·
Intermittent retesting is not necessary for cats with
confirmed negative infection status unless they have an opportunity for
exposure to infected cats or they become ill.
Diagnosis
of FeLV
Routine diagnostic screening for FeLV relies on
detection of the core viral antigen p27, which is produced abundantly in most
infected cats. In-clinic test kits detect soluble circulating antigen in
peripheral blood. In the early days of testing, results were more reliable when
serum or plasma rather than whole blood was tested (Barr
1996). However, with improvements in test technologies,
anticoagulated whole blood now appears also to be a suitable sample for testing
(Hartmann et al 2007). Antigen
tests should not be performed on tears or saliva because these tests are prone
to more errors (Hawkins
et al 1986, Lutz
and Jarrett 1987, Hawkins
1991). Soluble antigen tests can detect infection during
the early primary viremia phase. Most cats will test positive with soluble
antigen tests within 30 days of exposure (Jarrett
et al 1982), however, development of antigenemia is extremely
variable and may take considerably longer in some cats. When the results of
soluble antigen testing are negative but recent infection cannot be ruled out,
testing should be repeated a minimum of 30 days after the last potential
exposure. Alternatively, PCR can be performed on anticoagulated whole blood to
detect provirus. PCR is usually positive sooner than p27 antigen detection.
Kittens may be tested at any time because passively acquired maternal antibody
does not interfere with testing for viral antigen. However, kittens infected as
a result of maternal transmission may not test positive for weeks to months
after birth (Levy
and Crawford 2005).
IFA
tests on blood or bone marrow smears detect viral p27 antigen within infected
blood cells. IFA tests do not detect infection until secondary viremia is
established once bone marrow is infected. False-negative IFA results may occur
in leukopenic cats. Cats that have regressive infection and cats that resist
bone marrow infection also have negative IFA test results. False-positive
results may occur when smears are too thick, when background fluorescence is
high, and when the test is prepared and interpreted by inexperienced personnel.
Because the consequences of a positive screening test
are significant, confirmatory testing is recommended, especially in low-risk
and asymptomatic patients in which the possibility of a false-positive result
is higher (low positive predictive value) (Jacobson
1991). Negative screening test results are highly reliable
due to the high sensitivity of the tests and low prevalence of infection (high
negative predictive value).
Several options for confirmation of a positive
screening test are available. Virus culture is the gold standard for
identification of progressive FeLV infection but is not routinely available in
North America. A second soluble antigen test can be performed, preferably using
a test from a different manufacturer (Barr 1996, Hartmann
et al 2001). Some cats may be only transiently antigenemic and
may revert to negative status on soluble antigen tests (regressive infection) (Barr
1996). A positive IFA test on blood or bone marrow
indicates a cat is likely to remain persistently antigenemic.
Discordant
antigen test results may occur when results of soluble antigen tests and/or IFA
tests do not agree and may make determination of the true FeLV status of a cat
difficult. The most common scenario is with a positive soluble antigen test and
a negative IFA test. In most cases, such cats are truly infected. Discordant
results may be due to the stage of infection, the variability of host
responses, or technical problems with testing. The status of the cat with
discordant results may eventually become clear by repeating both tests in 60
days and annually thereafter until the test results agree. Cats with discordant
test results are best considered potential sources of infection for other cats
until their status is clarified.
PCR testing is offered by a number of commercial
laboratories for the diagnosis of FeLV. Technical errors can reduce the sensitivity
and specificity of PCR results. At this time, no comparative studies of the
diagnostic accuracy of different commercial laboratories offering FeLV PCR have
been completed. When performed under optimal conditions, real-time PCR can be
the most sensitive test methodology for FeLV and can help resolve cases in
which discordant serological test results have been obtained. Depending on how
the PCR is performed, it can detect viral RNA or cell-associated DNA (provirus)
and can be performed on blood, bone marrow, and tissues. In addition, PCR
testing of saliva has been shown to have high correlation with blood antigen
tests (Gomes-Keller et al 2006a,b).
Recent studies using real-time PCR have shown that 5–10% of cats negative on
soluble antigen tests were positive for FeLV provirus by PCR (regressive
infection) (Hofmann-Lehmann et al 2001, Gomes-Keller
et al 2006a). Although the clinical significance of
antigen-negative, PCR proviral DNA-positive status is still unknown, most such
cats appear to remain aviremic and non-antigenemic, do not shed virus, and are
unlikely to develop FeLV-associated diseases. Because FeLV provirus is
infectious (Chen et al 1998), all feline
blood donors should be tested for FeLV antigen by serology and for provirus by
real-time PCR.
Vaccination
against FeLV does not generally compromise testing, because FeLV tests detect
antigen and not antibodies. However, blood collected immediately following
vaccination may contain detectable FeLV antigens from the vaccine itself, so
diagnostic samples should be collected prior to FeLV vaccine administration
(Levy, unpublished data). How long this test interference persists is not known.
Diagnosis
of FIV
Cats infected with FIV have low viral loads throughout
most of their lives. Thus, development of rapid, in-clinic screening assays
based on antigen detection has not been possible. FIV produces a persistent,
life-long infection, so detection of antibodies in peripheral blood has been
judged sufficient for routine diagnostic screening if the cat has not been
previously vaccinated against FIV (Hartmann
1998, Levy et
al 2004). In-clinic test kits detect antibodies to different
viral antigens, most commonly p24. Most cats produce antibodies to FIV within
60 days of exposure, but development of detectable antibodies may be
considerably delayed in some cats (Barr
1996). A recent study showed that the performance of a
patient-side FIV/FeLV test kit for the detection of FIV infection was highly
accurate (Levy et al 2004). When the
results of antibody testing are negative but recent infection cannot be ruled
out, testing should be repeated a minimum of 60 days after the last potential
exposure.
Because the consequences of a positive screening test
are significant, confirmatory testing is recommended, especially in low-risk
and asymptomatic patients where the possibility of a false-positive result is
higher (Jacobson 1991). Negative
screening test results are highly reliable due to the high sensitivity of the
tests and the low prevalence of infection in most populations. Several options
are available for confirmation of a positive screening test. Virus culture is
the gold standard for identification of FIV infection but is not routinely
available in North America. A second soluble antibody test can be performed,
preferably using a test from a different manufacturer (Barr
1996,Hartmann
et al 2001). Western blot and IFA detect antibodies against a
range of viral antigens but were found to be less sensitive and specific than
in-clinic screening tests in one study (Levy et
al 2004).
The release of the first FIV vaccine (Fel-O-Vax FIV;
Fort Dodge Animal Health) has complicated the ability of veterinary
practitioners to diagnose FIV infections. Vaccinated cats produce antibodies
that cannot be distinguished, by any current commercially available antibody
test, from antibodies induced by natural infection (Levy et
al 2004). These antibodies are usually detected within a few
weeks of vaccination. Vaccine-induced antibodies have been shown to persist for
more than 4 years in some cats (Levy, unpublished data).
In this situation, determining whether a positive FIV
antibody test means the cat is truly infected with FIV, is vaccinated against
FIV but not infected, or is vaccinated against FIV and also infected might be
difficult. Recently, an experimental method of enzyme-linked immunosorbent
assay (ELISA) testing that detects antibodies to multiple FIV antigens was
developed in Japan (Kusuhara
et al 2007). Using this method, researchers were able to
distinguish FIV-vaccinated cats from FIV-infected cats with a high degree of
accuracy when testing serum samples from cats in both the United States and
Canada (Levy et al 2008). This test,
however, is not yet commercially available in North America.
PCR has been promoted as a method to determine a cat's
true status, but investigation of the sensitivity and specificity of the FIV
PCR tests offered by some laboratories has shown widely variable results (Bienzle
et al 2004). In one study, test sensitivities (the ability to
detect true positives) ranged from 41 to 93%, and test specificities (the
ability to detect true negatives) ranged from 81 to 100% (Crawford
et al 2005). Unexpectedly, false-positive results were higher in
FIV-vaccinated cats than in unvaccinated cats. Research is being focused on
improving the diagnostic accuracy of PCR for FIV.
Positive FIV antibody tests in kittens under 6 months
of age must be carefully interpreted. Antibodies from FIV-vaccinated queens are
passed to kittens that nurse on vaccinated queens (MacDonald
et al 2004). These vaccine-associated antibodies persist past
the age of weaning (8 weeks) in more than half of kittens. Kittens born to infected
queens or FIV-vaccinated queens also acquire FIV antibodies in colostrum.
Because kittens do not commonly become infected with FIV, most kittens that
test positive for FIV antibodies are not truly infected and will test negative
when re-evaluated several months later. Although FIV infection of kittens is
uncommon, it does occasionally occur, and kittens with FIV antibodies when over
6 months of age are considered to be infected. Delaying testing of kittens for
FIV until they are over 6 months of age may be tempting. However, the vast
majority of kittens test negative at any age and can be declared free of FIV
infection. Infected kittens, on the other hand, could be a source of infection
for other cats if they are not identified and segregated. Also, compliance by
both owners and veterinarians with retroviral testing recommendations remains
low, and delaying testing of newly acquired kittens would likely result in a
large number of cats never receiving FIV tests (Goldkamp
et al 2008).
Prevention of FeLV and FIV
Maximizing
prevention of retrovirus infection can be accomplished through a partnership
between veterinarians and pet owners. Testing and vaccination protocols, staff
education, client reminder programs, and pet owner educational efforts can help
contain the spread of these infections.
Traditionally, FeLV infection has been viewed as
primarily a concern for cats that are ‘friendly’ with other cats, because
close, intimate contact between cats facilitates transmission. This type of
contact occurs among cats as a result of nursing, mutual grooming, and sharing
of food, water, and litter pans. In contrast, FIV infection had been viewed as
a concern for cats that are ‘unfriendly’ with other cats, because the major
mode of transmission is through bite wounds. In reality, both viruses can be
spread among cats that are not known to fight as well as those that are prone
to aggressive behavior (Addie
et al 2000, Goldkamp
et al 2008).
FeLV
Vaccination
Several injectable inactivated adjuvanted vaccines, a
non-adjuvanted recombinant vaccine for transdermal administration (available in
the United States), and an injectable non-adjuvanted recombinant FeLV vaccine
(a different preparation from the United States product and available in
Europe) are commercially available. Reviews of independent studies of vaccine
efficacy indicate that the ability of any particular vaccine brand to induce an
immune response sufficient to resist persistent viremia varies considerably
between studies (Sparkes
1997, 2003).
Results of several studies indicate that FeLV vaccine-induced immunity persists
for at least 12 months following vaccination, although the actual duration of
immunity is unknown and may be longer (Hofmann-Lehmann
et al 1995, Hoover
et al 1996, Harbour
et al 2002).
Because
sufficient protection is not induced in all vaccinates, vaccination against
FeLV does not diminish the importance of testing cats to identify and isolate
those that are viremic. Therefore, the FeLV infection status of all cats,
including vaccinated cats, should be determined. In addition, cats should be
tested for FeLV infection before initial vaccination and whenever the
possibility exists that they have been exposed to FeLV since they were last
vaccinated. Administering FeLV vaccines to cats confirmed to be FeLV-infected
is of no value.
FeLV vaccines should be considered non-core vaccines
and are recommended for cats at risk of exposure (eg, cats permitted outdoors,
cats residing in multiple-cat environments in which incoming cats are not
tested prior to entry, cats living with FeLV-infected cats). However,
vaccination of all kittens is highly recommended because the lifestyles of
kittens frequently change after acquisition and they may subsequently become at
risk of FeLV exposure (Richards
et al 2006). Kittens are also more likely than adult cats to
develop progressive infections if exposed to FeLV.
When
FeLV vaccination is determined to be appropriate, a two-dose primary series is
recommended, with the first dose administered as early as 8 weeks of age
followed by a second dose administered 3–4 weeks later. A single booster
vaccination should be administered 1 year following completion of the initial
series and then annually in cats as long as they remain at risk of exposure.
Although FeLV vaccines have been shown to protect
against progressive infection to various degrees, they do not appear to prevent
infection. Using real-time PCR, vaccinated cats were found to become positive
for circulating proviral DNA as well as plasma viral RNA subsequent to FeLV
exposure, even though they did not develop persistent viremia (Torres
et al 2005, Hofmann-Lehmann
et al 2006, 2007).
Thus, FeLV vaccination does not necessarily induce sterilizing immunity.
Nonetheless, efficacious FeLV vaccines are of great clinical importance because
protection against persistent viremia may prevent FeLV-associated fatal
diseases.
FIV
Vaccination
FIV has proven to be a difficult agent to immunize
against, in part because FIV vaccines do not induce broad cross-protective
immunity against viruses from other strains or clades. Only a single vaccine is
currently available for prevention of FIV infection. The vaccine is a
whole-virus, dual subtype (clades A and D), inactivated product combined with
an adjuvant. The vaccine is licensed for the vaccination of healthy cats 8
weeks of age or older as an aid in the prevention of infection with FIV. In
licensing trials required by the United States Department of Agriculture, when
cats were challenged with a heterologous clade A FIV subtype 1 year after the
initial vaccination series, the vaccine yielded a preventable fraction (defined
as the proportion of cats protected by vaccination in excess of the proportion
that is naturally resistant) of 82% (Huang
et al 2004). Results of two subsequent studies indicate 100%
protection against infection with two subtype B FIV strains (Kusuhara
et al 2005, Pu et
al 2005). Results of a third study in which cats were
challenged with subtype A FIV indicated that all vaccinated cats and control
cats became infected (Dunham
et al 2006).
FIV
vaccines are non-core vaccines and may be considered for cats whose lifestyles
put them at high-risk of infection, such as outdoor cats that fight or cats
living with FIV-infected cats. An initial series of three doses is administered
subcutaneously 2–3 weeks apart. Annual revaccination is recommended subsequent
to the initial series if the risk of infection continues.
Clients
should be informed that vaccinated cats will have positive FIV test results,
and the decision to vaccinate should be reached only after careful
consideration of this implication. If the decision falls in favor of
vaccination, cats should test negative immediately prior to vaccination. A
permanently placed identification microchip and collar are recommended for all
cats to increase the chance of returning lost cats to their owners. Microchip
databases can also record FIV vaccination histories. This information can be
used by animal shelters to help assess the significance of positive FIV test
results when shelters screen cats prior to adoption.
Limiting
Transmission in the Veterinary Practice
Retroviruses are unstable outside their host animals
and can be quickly inactivated by detergents and common hospital disinfectants
(Francis et al 1979, August
1991, van
Engelenburg et al 2002, Moorer
2003, Kramer
et al 2006, Terpstra
et al 2007). However, retroviruses in dried biological deposits
can remain viable for more than a week. Simple precautions and routine cleaning
procedures will prevent transmission of these agents in veterinary hospitals.
All infected patients should be housed in individual cages and may be
maintained in this manner in the general hospital population. Because they may
be immune-suppressed, they should not be housed in an isolation ward with cats
carrying contagious diseases.
Animal caretakers and other hospital staff members
should wash their hands between patients and after handling animals and
cleaning cages. Both FeLV and FIV can be transmitted in blood transfusions.
Therefore, all blood donors should be confirmed free of infection (Wardrop
et al 2005).
Dental and surgical instruments, endotracheal tubes,
and other items potentially contaminated with body fluids should be thoroughly
cleaned and sterilized between uses (Druce
et al 1997). Fluid lines, multi-dose medication containers, and
food can become contaminated with body fluids (especially blood or saliva), and
should not be shared among patients.
Limiting
Transmission at Home
FeLV-infected
cats should be confined indoors so they do not pose a risk of infection to
other cats and so that they are protected against infectious hazards in the
environment. If a FeLV-positive cat is identified in a household, the best
method of preventing spread to other cats in the household is to isolate the infected
cat in a separate room and to prevent the infected cat from interacting with
its housemates. A simple screen or chain-link barrier is adequate to prevent
viral transmission in the laboratory setting (Levy, unpublished data).
If
owners choose not to separate housemates, uninfected cats should be vaccinated
against FeLV in an attempt to enhance their natural level of immunity. The cats
should be kept separated until at least 2 months after completion of the
primary immunization series to allow time for effective immunity to develop.
However, no FeLV vaccine protects 100% of cats against FeLV infection. FeLV can
be transmitted vertically from an infected queen to her kittens in utero or via
infected milk. Infected queens should not be bred and should be spayed if their
condition is sufficiently stable to permit them to undergo surgery.
Generally, cats in households with stable social
structures where housemates do not fight are at a low-risk for acquiring FIV
infection, but a high rate of transmission within a household without observed
fighting has been reported (Addie
et al 2000). Therefore, separation of infected cats from
uninfected housemates is recommended to eliminate the potential for FIV
transmission. If separation is not possible, and to reduce the risk of
territorial aggression, no new cats should be introduced in the household.
Experimentally, FIV has been shown to be vertically transmitted by infected
queens to their kittens (Pu et
al 1995, O'Neil
et al 1995, Allison
et al 2003). Although this is apparently true only for a few
specific strains of FIV and is uncommon in nature, infected queens should not
be bred and should be spayed if their condition is sufficiently stable to
permit them to undergo surgery.
Considerations for Breeding Catteries
The
prevalence of retrovirus infections in the controlled environments of catteries
appears to be low, particularly since the advent of test and removal programs
for FeLV in the 1970s. However, ongoing vigilance is required to prevent
introduction of FeLV or FIV into the cattery. Certain circumstances in
catteries facilitate transmission of infectious diseases, such as group living,
mingling of kittens with older cats, close contact of cats during mating, the
occasional introduction of new cats, and the practice of sending queens to
other catteries for breeding.
Only
healthy cats should be used for breeding, and the retrovirus status of all cats
in the cattery should be known (whether breeding or non-breeding). When testing
is performed in the cattery for the first time, all cats should test negative
on two tests, 60 days apart. Infected cats should be removed from the cattery.
All newly acquired kittens and cats should be placed in isolation and tested
for FeLV and FIV on arrival. Ideally, they should remain isolated until a
second negative test is obtained 60 days later, particularly if they originate
from a cattery with unknown retrovirus status.
Queens
sent to another facility for mating should be tested before leaving the cattery
and should be sent to mate only with a tom that has tested negative for FeLV
and FIV. Upon return to the home cattery, the queen should be kept in isolation
and retested in 60 days.
Cat
shows are not significant sources of retrovirus infection, because cats on
exhibition are housed separately and the viruses are susceptible to the
disinfectants that are commonly employed. In addition, environmental
contamination of surfaces is not a risk due to the fragile nature of
retroviruses. Therefore, cats that have left the cattery solely for the purpose
of a cat show do not need to be retested.
In
catteries that follow testing guidelines and maintain retrovirus-negative
status, vaccination against FeLV or FIV is not necessary, as long as no cats
have access to the outdoors. Time and resources should be focused on
maintaining a retrovirus-negative cattery through testing. Some catteries do
not maintain breeding toms, and rely totally on stud services from other
catteries. In such circumstances, vaccination of queens against FeLV may be
considered in addition to testing of queens that leave the cattery for stud
service. Vaccination against FIV is not recommended, because the infection is
uncommon in catteries and vaccination interferes with current test methodologies.
Considerations for Cat Shelters
Although the prevalence of FeLV and FIV in shelters
mirrors the relatively low rates found in pet cats, thousands of infected cats
are likely to pass through shelters each year (Levy et
al 2006b). Shelters should have policies in place for testing,
prevention, and responding to positive test results.
The
sheltering industry is currently in a state of flux as growing support for ‘no
kill’ policies stimulates discussion about what constitutes an ‘untreatable’ or
‘unsavable’ animal. Using the strictest definition of euthanasia as an act of
mercy for alleviating unremitting suffering, a growing number of shelters are
classifying healthy FeLV-infected and FIV-infected cats as adoptable. This has
created new challenges for shelter facilities, because finding homes for
infected cats often takes longer. When shelter space is limited, longer
resident times may lead to lower overall adoption rates. Sanctuaries devoted to
long-term care of infected cats have been developed as an alternative and
present their own set of challenges for optimal care and environmental
enrichment.
Although this document broadly recommends testing all
cats for retroviral infection, an exception exists for feral cats in
trap-neuter-return (TNR) programs. The prevalence of infection is similar in
outdoor pet cats and feral cats; so feral cats do not present an increased
threat to pets (Levy et
al 2006b). Additionally, neutering reduces two common modes of
transmission: queen to kitten for FeLV and fighting among males for both FeLV
and FIV (Levy 2000, Levy
and Crawford 2005). Because population control of feral cats requires
commitment to neutering the largest number of cats possible, many TNR programs
do not routinely test feral cats (Wallace
and Levy 2006).
Testing
for FeLV and FIV in Shelters
Diagnosis
of FeLV and FIV in shelter situations follows the same principles as in pet
cats. Ideally, all cats would be tested upon entry to the shelter or prior to
adoption. All cats entering shelters should be considered potentially infected,
regardless of the environment from which they originated. Because the background
of most shelter cats is unknown, retesting cats 60 days after the initial test
in case of recent exposure is advisable. This also applies to unweaned orphaned
kittens, which may have been infected from the queen or another cat but test
negative at the time of admission to the shelter. These kittens should be
retested prior to adoption. Cats that are returned to the shelter following a
failed adoption should also be retested.
Although
screening tests are commonly used in shelters, confirmatory tests pose a greater
challenge. Increased costs, delays, and difficulty in interpreting discordant
results are reasons many shelters do not pursue confirmatory testing.
Currently, the inability to distinguish FIV-vaccinated cats from those that are
infected or both vaccinated and infected is a major concern for shelters.
Testing
at admission is optional for cats that are housed in single-cat cages. Some
shelters routinely test cats at the time of adoption instead of at admission,
particularly if a substantial proportion of cats are not expected to be
adopted. In some situations, limited shelter resources do not permit testing of
all cats for both FeLV and FIV prior to adoption. In such cases, shelters may
place priorities on testing higher-risk cats such as sick cats, adult males,
and cats suspected to be exposed to infected cats. If limited testing or no
testing is employed, cats should be housed singly and post-adoption testing
recommended. In such cases, the AAFP recommendation to test all newly adopted
cats should be clearly explained and documented to the adopter. Arrangements
should be made by the adopter to have the new pet tested by his or her own
veterinarian as soon as possible. The new pet should be kept separate from
other cats until the test result is known and preferably until a second test is
performed 60 days later. Although the vast majority of sheltered cats are free
of infection, post-adoption testing is likely to result in some new pet owners
confronting difficult decisions about what to do with a newly adopted cat that
is subsequently diagnosed with a retrovirus infection. If one cat in a litter
or group is later reported to be infected, the adopters of other cats with
exposure to the infected cat should be contacted and informed.
Cats
should have negative test results for both FeLV and FIV prior to being
introduced to group housing. A quarantine period of 60 days followed by
retesting prior to introduction to the group is ideal but not always practical
in a shelter setting. Resident cats in foster homes should be tested before
foster cats are added to the household.
In
shelters or sanctuaries that group-house large numbers of cats for long
periods, annual retesting of resident cats is a good practice. Cats kept in
multi-cat environments with cats of unknown background constitute a high-risk
population even if all of the cats are tested when they are first added to the
group. Because tests are not 100% accurate, a cat could be admitted to the
group with an undiagnosed infection.
The presence of infection varies within individual
litters, feral cat colonies, and households. Some shelters attempt to conserve
resources by testing only a queen and not her kittens or by testing only a few
members of a litter or household. Testing one cat as a proxy for another is inappropriate,
however, and shelter medical records should individually identify each cat and
accurately reflect the actual testing procedures performed. Testing a small
number of cats within a colony to determine whether FeLV or FIV is present is
also inappropriate, because the prevalence of retroviral infections is low even
among feral cats (Levy et
al 2006b).
Because
currently no test can distinguish FIV antibodies induced by infection compared
to those induced by vaccination, shelters have the difficult task of
determining the true infection status of stray cats that are admitted without
medical histories and that test positive for FIV antibodies. In some cases, the
history of FIV vaccination may be recorded in a microchip database that can be
accessed if the cat is microchipped. However, even if cats are known to have
been vaccinated against FIV, determining whether they are not also infected is
not usually possible. This is a challenge for shelters for which no current
solution exists.
Test
procedures must be performed as indicated by the manufacturer to maintain
accuracy. Procedures such as pooling multiple samples for use in a single test
reduce test sensitivity and should not be performed.
Testing recommendations:
·
Ideally, all cats in shelters will be tested for FeLV
and FIV.
·
Testing at admission is optional for singly housed
cats.
·
Testing is highly recommended for group-housed cats.
·
Testing, if not performed prior to adoption, should be
recommended to the new owner before the cat is exposed to other cats.
·
Testing should be repeated 60 days after the initial
test and annually for cats kept in long-term group housing.
·
Testing one cat as a proxy for another or pooling
samples from multiple cats for testing is inappropriate. Each cat should be individually
tested.
·
Testing of both foster families' and adopters' own
resident cats should occur prior to fostering or adopting a new cat.
·
Testing is optional in feral cat TNR programs.
Prevention
of FeLV and FIV Transmission in Shelters
FeLV and FIV differ from other infectious diseases of
importance in shelters, such as panleukopenia virus, calicivirus, and
herpesvirus, because the retroviruses are easily inactivated with routine
disinfection and are not spread by indirect contact. However, FeLV and FIV are
efficiently transmitted iatrogenically by small amounts of contaminated body
fluids, particularly blood and saliva (Druce
et al 1997). For this reason, surgical instruments and needles
should never be shared between cats, even those within the same litter, without
effective sterilization. Similarly, all endotracheal tubes, breathing circuits,
dental instruments, and other potentially contaminated equipment should be
disinfected between each patient, even among cats from the same environment or
litter.
Vaccination
against FeLV is generally not recommended in shelters in which cats are
individually housed, because of the low-risk of viral transmission. In such
shelters, resources are generally better spent on testing, and the decision to
vaccinate is best left to the adopter and the cat's new veterinarian based on
the cat's risk profile in its new home. In facilities in which cats are
group-housed, such as in some shelters and foster homes, FeLV vaccination is
highly recommended. High turnover of cats from multiple unknown backgrounds
increases the risk for FeLV transmission in group housing and foster homes,
especially when quarantine and retesting at a later time is not possible.
For
the same reason, vaccination against FIV is not generally recommended in
typical single-cat housing. In addition, vaccine-induced positive antibody test
results make future confirmation of the true FIV infection status of vaccinated
cats difficult for shelters.
Control recommendations:
·
FeLV vaccination is optional for singly housed cats.
·
FeLV vaccination is highly recommended for all cats
housed in groups and for both foster cats and permanent residents in foster
homes.
·
Cats should test negative for FeLV prior to
vaccination.
·
Vaccination is not 100% effective against FeLV and
should never be used in place of a test-and-segregate program.
·
In contrast to the case for feline panleukopenia, herpesvirus,
and calicivirus vaccines, the value of a single FeLV vaccine has not been
determined. Therefore, FeLV vaccination is not recommended for feral cat TNR
programs if program resources are needed for higher priorities.
·
FIV vaccination is not recommended for use in
shelters.
·
Strict adherence to universal precautions is required
to prevent iatrogenic transmission of retroviruses in the shelter environment
via contaminated equipment and secretions.
·
Cats used for blood donation in shelters should be proved
free of retroviral infection prior to donating blood.
Management of Retrovirus-infected Cats
Both FeLV-infected and FIV-infected cats can live many
years with proper care and may succumb at older ages from causes unrelated to
their retrovirus infections. Long-term monitoring of a 26-cat household with
endemic FeLV and FIV revealed that all FeLV-infected cats died within 5 years
of diagnosis, but FIV infection did not affect survival in this group (Addie
et al 2000). A large study compared the survival of more than
1000 FIV-infected cats to more than 8000 age- and sex-matched uninfected
control cats (Levy et
al 2006a). Of cats that were not euthanased around the time of
diagnosis, the median survival of the FIV-infected cats was 4.9 years compared
to 6.0 years for the control cats. A comparison between more than 800 FeLV-infected
cats and 7000 controls revealed that the median survival of FeLV-infected cats
was 2.4 years compared to 6.3 years for controls (Levy et
al 2006a). With proper care, many retrovirus-infected cats may
live for several years with good quality of life. Thus, a decision for
treatment or for euthanasia should never be based solely on the presence of a
retrovirus infection.
FIV- and FeLV-infected cats are subject to the same
diseases that befall cats free of those infections, and a disease diagnosed in
a retrovirus-infected cat may not be related to the retrovirus infection (Levy
2000, Levy
and Crawford 2005). However, in all cats, healthy or sick, FIV and FeLV
status should be known because the presence of a retrovirus infection impacts
their health status and long-term management.
Cats infected with FIV, FeLV, or both should be
confined indoors to prevent spread to other cats in the neighborhood and
exposure of affected cats to infectious agents carried by other animals. Good
nutrition, husbandry, and an enriched lifestyle are essential to maintain good
health (August 1991, Overall
et al 2005). The cats should be fed a nutritionally balanced and
complete feline diet. Raw meat and dairy products should be avoided because the
risk of food-borne bacterial and parasitic diseases is greater in
immunosuppressed individuals. A program for routine control of gastrointestinal
parasites, ectoparasites, and heartworms, where applicable, should be
implemented (Companion
Animal Parasite Council 2007).
Cats infected with a retrovirus should receive
wellness visits at least semiannually to promptly detect changes in their
health status. Veterinarians should obtain a detailed history to help identify
changes requiring more intensive investigation and should perform a thorough
physical examination at each visit. Special attention should be paid to the
oral cavity because dental and gum diseases are common in retrovirus-infected
cats (Bellows, unpublished data). Lymph nodes should be evaluated for changes
in size and shape. All cats should receive a thorough examination of the
anterior and posterior segments of the eye (Willis
2000). The skin should be examined closely for evidence of
external parasitic infestations, fungal diseases, and neoplastic changes. Body
weight should be accurately measured and recorded because weight loss is often
the first sign of deterioration in a cat's condition.
A
complete blood count should be performed annually for FIV-infected cats and at
least semiannually for FeLV-infected cats because of the greater frequency of
virus-related hematologic disorders in FeLV-infected cats. Serum biochemical
analyses and urinalyses should be performed annually for both FeLV and FIV
infections; urine samples should be collected by cystocentesis so that
bacterial cultures can be performed if indicated. Fecal examinations should be
performed for cats with a history of possible exposure to gastrointestinal
parasites or pathogens.
‘Routine vaccination’ of retrovirus-infected cats is a
subject of debate. Although little evidence suggests modified live-virus
vaccines are problematic, inactivated vaccines are recommended because
live-virus vaccines theoretically might regain their pathogenicity in
immune-suppressed animals (Buonavoglia
et al 1993, Reubel
et al 1994, Richards
et al 2006). Healthy FIV-infected cats have been shown to have
similarly adequate immune responses to vaccination compared to uninfected cats
(Dawson et al 1991,Lehmann
et al 1991, Fischer
et al 2007). Vaccination of FIV-infected cats may lead to
stimulation of the immune system and subsequent increased FIV replication,
although the clinical significance of this observation is unknown (Lehmann
et al 1992, Reubel
et al 1994). Some cats infected with FeLV may not adequately
respond to vaccination (Franchini
1990). In general, vaccine selection and immunization
intervals for cats with FeLV or FIV infection should be selected based on
individual risk assessments using guidelines developed for cats in general (Richards
et al 2006).
Sexually intact male and female cats should be
neutered to reduce stress associated with estrus and mating behaviors. Neutered
animals are also less likely to roam outside the house or interact aggressively
with their housemates. Surgery is generally well-tolerated by infected cats
that are not showing any clinical signs of disease. A thorough examination and,
ideally, pre-anesthetic blood testing should be performed before surgery.
Perioperative antibiotic administration should be considered for infected cats
undergoing dental procedures and surgeries, because of their potentially
immunosuppressed state. Appropriate analgesia should be administered not only
to cats undergoing invasive procedures but also to cats with chronic pain due
to retroviral-associated conditions such as stomatitis, uveitis, and neoplasia
(Hellyer et al 2007).
Clinical illness in cats with FeLV or FIV infection
may be a primary effect of retroviral infection (such as lymphoma or pure red
cell aplasia), a secondary disease associated with immune dysfunction (such as
opportunistic infections or stomatitis), or unrelated to the viral infection.
Prompt and accurate diagnosis is essential to allow early therapeutic
intervention and a successful treatment outcome. Therefore, more intensive
diagnostic testing should proceed earlier in the course of illness for infected
cats than that might be recommended for uninfected cats. Many cats infected
with FeLV or FIV respond as well as their uninfected counterparts to appropriate
medications and treatment strategies, although a longer or more aggressive
course of treatment may be needed (Levy et
al 2006a)
Corticosteroids and other immune-suppressive drugs
should be administered only to those patients for whom their use is clearly
indicated. In severe stomatitis, which commonly occurs in retrovirus-infected
cats, extraction of all teeth is preferred over long-term use of
corticosteroids. Griseofulvin has been shown to cause bone marrow suppression
in FIV-infected cats and should not be used for treatment of fungal infections
(Shelton et al 1990).
Highly active antiretroviral therapy (HAART) cocktails
are the mainstay of treatment in HIV-infected patients and result in longer
survivals and improved quality of life. Antiviral therapy has also been used in
retrovirus-infected cats, although the drugs available to cats are limited and
tend to be more toxic in cats than in human beings (Hartmann
2006). Drugs aimed at modulating the immune system are
commonly used in cats and are proposed to restore compromised immune function,
thereby allowing the patient to control viral burden and recover from
associated clinical syndromes. Unfortunately, only a few large long-term
controlled studies in naturally infected cats have shown durable benefit using
either antiviral drugs or immunomodulators.
The only antiviral compound routinely used in both
retrovirus infections is zidovudine (AZT), a nucleoside analog (thymidine
derivative) that blocks the viral reverse transcriptase enzyme. AZT has been
shown to effectively inhibit FeLV and FIV replication in vitro and in vivo; it
can reduce plasma virus load and improve immunological and clinical status,
particularly in cats with neurological signs or stomatitis. AZT is used at a
dosage of 5–10 mg/kg PO or SC q 12 h. The higher dose should be carefully used
in FeLV-infected cats because side effects, particularly non-regenerative
anemia, can develop (Hartmann
et al 1992, 1995a,b, Hartmann
2005).
Feline interferon omega (Virbagen; Omega, Virbac
Animal Health) has been available for use in a few countries for several years.
In a placebo-controlled field study, FeLV-infected cats treated with interferon
omega (106 IU/kg
SC q 24 h for five consecutive days repeated three times with several weeks
between treatments) were more likely to be alive at 1 year compared to
placebo-treated cats (de Mari
et al 2004). The mechanism for the survival advantage is
undetermined because no virological parameters were measured. No effect on
survival in FIV-infected cats was observed.
Natural human interferon alpha (Alfaferone; Alfa
Wasserman, Italy) was used in clinically ill cats naturally infected with FIV
(50 IU on the oral mucosa daily for 7 days on alternating weeks for 6 months,
followed by a 2-month break, and then repetition of the 6-month treatment).
Supportive treatments (eg, antibiotics and parasiticides) were allowed. Of the
53 cats that entered the study results were reported for 30 of the cats. Three
cats were co-infected with FeLV. All but one of the 24 cats in the treatment
group for which results were reported were alive at 18 months compared to only
one of the six placebo-treated cats. The apparent survival benefit associated
with interferon alpha treatment could not be explained by improvements in viral
burden, CD4+ T-lymphocyte counts, or hematological results (Pedretti
et al 2006).
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