Download Feline Upper Respiratory Tract Pathogens

166
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Vol. 23, No. 2 February 2001
Article #4 (1.5 contact hours)
Refereed Peer Review
FOCAL POINT
★Feline herpesvirus-1 (FHV1) and
feline calicivirus (FCV) can be
associated with various infections
that can be challenging to
diagnose and treat.
KEY FACTS
■ The carrier state is crucially
important in the maintenance
and spread of both FHV1 and
FCV, p. 167.
■ FHV1 and FCV may cause similar
clinical signs, although some
manifestations appear to be
unique to each virus, potentially
aiding in diagnosis, p. 169.
■ Despite the advent of new
diagnostic tests, the diagnosis
of FHV1 and FCV is confounded
by the relative lack of virus in
chronic cases and the inability
of tests to differentiate between
symptomatic and healthy carrier
cats, p. 171.
■ Using virus isolation or
polymerase chain reaction can
aid in assessing prognosis and
implementing management
strategies, p. 171.
■ Indiscriminate use of antiviral
compounds is not recommended
because they may be toxic or
poorly effective, p. 171.
Feline Upper Respiratory
Tract Pathogens:
Herpesvirus-1
and Calicivirus
University of Minnesota
Jane E. Sykes, BVSc (Hons), PhD
ABSTRACT: Feline herpesvirus-1 and feline calicivirus are common causes of feline upper respiratory tract disease and can cause clinically indistinguishable syndromes. However, they
differ in their physical properties, epidemiology, and spectrum of clinical signs; and the differences can affect the diagnosis, prognosis, and management of these infections. The availability and sensitivity of diagnostic tests also differ for each virus. Diagnosis of both infections can
be difficult and is best achieved by combining patient history, physical examination, and microbiologic assay results. Treatment is primarily symptomatic. Vaccination does not prevent
infection but can help minimize the severity of clinical signs and duration of shedding.
C
ats with both acute and chronic upper respiratory tract disease (URTD)
are commonly seen in private and referral practices. The general syndrome varies in severity. When severe, it may be associated with considerable morbidity and mortality; it is therefore a concern of breeding and boarding cattery owners. Although the introduction of vaccines targeting feline
herpesvirus-1 (FHV1) and feline calicivirus (FCV) in the mid-1970s may have
reduced the overall disease severity, the vaccines do not prevent infection and
shedding of virus and URTD may still occur. Despite the increasing availability
of such molecular diagnostics as polymerase chain reaction (PCR), diagnosis and
treatment of many cases of chronic feline URTDs remain frustrating.
This article provides an update on the epidemiology, clinical presentations,
and antemortem diagnosis and management of FHV1 and FCV, common causes of feline URTD. Chlamydophila felis (previously known as feline Chlamydia
psittaci) is another common cause of feline URTD. In addition, recent research
suggests that Bordetella bronchiseptica may act as a primary upper respiratory
tract pathogen in cats under certain circumstances, particularly in young kittens
and in overcrowded, stressful environments; however, the relative importance of
B. bronchiseptica infection remains unclear.1 The role of Mycoplasma infection in
cats with URTD is also poorly defined, and some authors suggest that Mycoplasma species mainly act as secondary invaders.
Compendium February 2001
CAUSES
Feline Herpesvirus-1
Feline herpesvirus-1 has a double-stranded DNA
genome surrounded by an icosahedral capsid, which is
enveloped by a delicate lipid membrane containing several different glycoproteins. The fragility of the envelope limits the survival of FHV1 in the environment to
only 18 hours in moist conditions and makes it highly
susceptible to destruction by common disinfectants.
Feline herpesvirus-1 isolates worldwide are remarkably
similar and belong to a single serotype. However, the existence of attenuated vaccine strains suggests that the virulence of different isolates may vary. FHV1 has recently
been divided into four groups based on restriction endonuclease patterns and the presence or absence of a 36kDa immunogenic protein.2 The relationship between
these groups and virulence has not been determined.
Feline Calicivirus
Feline calicivirus is a nonenveloped, single-stranded
RNA virus with a roughly spherical capsid that is studded with cup-shaped depressions. The virus is more resistant in the environment than is FHV1, surviving up
to 10 days. It is inactivated by iodine, hypochlorite,
and glutaraldehyde but not by quaternary ammonium
products, anionic detergents, and ethanol.3
Although considerable antigenic heterogeneity occurs
among FCV isolates, the degree of cross-reactivity is
sufficient for them to be classified as a single serotype.
Isolates worldwide apparently fall into a single, diverse
group based on nucleotide sequence analysis.4
PATHOGENESIS AND EPIDEMIOLOGY
Feline herpesvirus-1 and FCV infections may be acquired by contact with an acutely infected cat, organisms persisting in the environment, or a carrier cat (see
the Carrier State section). Cats produce relatively ineffective aerosols that travel a maximum of approximately
4 feet.5 The chance of contact with an acutely infected
cat is increased when many cats are housed together
(e.g., breeding and boarding catteries, multiple-cat
households). Catteries also provide greater opportunity
for indirect transmission through contamination of human hands, feeding and grooming utensils, and other
fomites.
Both viruses replicate mainly in the tonsils and respiratory tissue. Viremia may occur with FCV infection
and spread to other viscera. Replication of FHV1 is
usually restricted to the upper respiratory tract, but
generalized disease with viremia can occur in debilitated animals. In addition to the nasal, conjunctival, and
oral shedding common to both viruses, FCV is shed in
the feces and occasionally in the urine.
Small Animal/Exotics 167
Carrier State
The ability of FHV1 and FCV to persist in the tissue
of subclinically infected cats is crucial to their pathogenic success. The mechanism of persistence in each
case is different and influences the prognosis, diagnosis,
and management decisions.
Over 80% (and probably 100%) of cats infected with
FHV1 develop latent infections in which the virus enters a nonreplicative state that persists for the life of the
animal.6,7 In cats, sites of latency include the trigeminal
ganglia, optic nerves, optic chiasm, olfactory bulb,
lacrimal gland, cornea, tonsils, and nasal turbinates.7,8
Reactivation of virus shedding occurs with or without
concurrent clinical signs in approximately 50% of infected cats. It may occur spontaneously or after natural
or artificial (corticosteroid-induced) stress. Travel (e.g.,
to a cat show, stud, or veterinarian) can be sufficient
stress to induce reactivation. Parturition and lactation
are particularly stressful, allowing spread of virus from a
queen to the kittens. Shedding occurs 4 to 11 days after
the stress and lasts 1 to 2 weeks.6 If clinical signs occur,
they tend to be less severe than are those after the initial
infection. The precise mechanism underlying reactivation is unknown, and the frequency varies among individuals. Humans with frequent recurrences of herpes
simplex may have depressed cell-mediated immunity.9
In contrast to FHV1, shedding of FCV by persistently infected cats is continuous and not caused by stress.
Viral shedding occurs from the oropharynx and fluctuates with time; the level of excretion varies among individual cats.10 The proportion of cats that are shedding
decreases over time. In one study, 50% of cats had
ceased shedding 75 days after infection. In some cats,
shedding may be lifelong. Factors influencing the commencement and termination of the carrier state are unclear. Coinfection with feline immunodeficiency virus
can prolong shedding of FCV.11 In one study, persistent
shedding by queens abruptly ceased after their kittens
began to shed virus; it was suggested that increased exposure to FCV may have stimulated an immune response in the queens that led to elimination of the
virus.12 However, vaccination does not eliminate the
carrier state. It was recently shown that a single cat can
be infected with multiple FCV variants at the same
time.13 Each variant is derived from the original infecting strain as a result of genetic mutation, drift, and selection pressures. The emergence of these antigenic
variants, driven by immune pressure, may be responsible for allowing FCV variants to persist despite the immune response.
Prevalence
Before the introduction of respiratory viral vaccines,
DISEASE TRANSMISSION ■ GENETIC STRUCTURE OF VIRUSES ■ SITES OF LATENCY
168 Small Animal/Exotics
Compendium February 2001
serologic studies revealed that
pressive illness or infection
50% to 70% of cats had antiwith other respiratory pathobodies against FHV1. In congens (e.g., B. bronchiseptica)
trast, a recent study using a
and secondary bacterial insensitive ELISA found that
vaders can also dramatically in97% of client-owned cats had
fluence the severity of disease.
detectable FHV1 IgG and
Respiratory and
95% had titers greater than
32. The magnitudes of these
Ocular Disease
titers were higher than were
Signs of URTD common
expected from vaccination
to both FHV1 and FCV inalone, suggesting that natural
fections include serous or
exposure to FHV1 occurs Figure 1—Corneal sequestrum in a cat. (Courtesy of mucopurulent nasal discommonly and boosts titers Robert Larocca, DVM, University of Minnesota)
charge and sneezing and, less
induced by vaccination.14
commonly, coughing and/or
Numerous studies have indyspnea. Both FHV1 and
vestigated the prevalence of respiratory viruses in both
FCV cause conjunctivitis with conjunctival hyperemia,
diseased and asymptomatic cats. Comparisons between
blepharospasm, serous to mucopurulent ocular disstudies are difficult because prevalence is highly depencharge, and chemosis. Signs may be acute or chronic.
dent on the sensitivity and specificity of the assay used
Depression, anorexia, hypersalivation, and pyrexia may
for diagnosis, anatomic site sampled (conjunctival veralso be present in cats with acute infections. In young
sus oropharyngeal), number of cats sampled, seasonal
cats, damage to the upper respiratory tract epithelium
variation of disease, and clinical criteria used to define a
and osteolysis of the nasal turbinates may cause persiscase (e.g., acute, chronic). Most studies have used virus
tent or recurrent bacterial rhinitis and sinusitis.
isolation. Reports of the prevalence of FHV1 and FCV
Feline herpesvirus-1 may be associated with corneal
in cats with URTD have generally ranged from 10% to
ulceration and keratitis. Dendritic ulcers are branchlike
34% and 20% to 53%, respectively. In healthy cats, the
and result from limited viral replication in the corneal
prevalence of FCV has ranged from 8% of household
epithelium. The cause of the branching pattern is uncats to 24% of show cats.15 The prevalence of FHV1 in
clear. Dendritic ulcers are generally considered pathognomonic for herpes simplex virus and FHV1 infection;
asymptomatic cats has generally been lower (0% to
however, ocular adenovirus infection was recently asso1.75%) than that for FCV, reflecting the nature of the
ciated with dendritic ulceration in humans.19 Only
carrier state for each virus. However, in one recent
study, the prevalence of FHV1 in conjunctival swabs
some infected cats develop keratitis. Researchers suspect
from asymptomatic cats using fluorescent antibody
an immune-mediated pathogenesis that may be directtesting or virus isolation was higher (10.9% and
ed against both residual virus antigen in the corneal
28.3%, respectively) and not significantly different
stroma and the cornea itself. There is evidence that
from that in diseased cats.16 Using PCR, the prevalence
FHV1 may be involved in some cases of uveitis, corneal
sequestration (Figure 1), and eosinophilic keratitis.20,21
of FHV1 in asymptomatic animals has ranged from
0% to 31%, with the highest prevalence being reported
Stomatitis
with nested PCR (see the Diagnosis section). The exisUlcerative glossitis is more common and severe in
tence of a high prevalence of FCV and possibly FHV1
cats with FCV infection but may be associated with
infection in asymptomatic cats requires consideration
FHV1 infection. I have noted severe pharyngitis associwhen interpreting positive test results in diseased cats.
ated with FHV1 infection without concurrent signs of
URTD.
CLINICAL FEATURES
Acute disease caused by FCV and FHV1 infection ocA small proportion of FCV carriers develop chronic
curs after an incubation of 2 to 10 days. The nature and
lymphoplasmacytic or chronic ulceroproliferative stomseverity of signs may depend on the infecting strain, alatitis (Figure 2), which is often refractory to therapy.
though examination of large numbers of FCV strains has
Coinfection with FIV may also play a role in the develfailed to show a clear link between disease manifestation
opment of chronic stomatitis.22
and antigenic and genetic heterogeneity of the FCV capsid
protein.17,18 The most severe signs tend to occur in very
Dermatologic Disease
Skin and nasal ulceration is possible with both FHV1
young or elderly debilitated cats. Concurrent immunosupPREVALENCE OF VIRUSES ■ ACUTE DISEASE ■ SIGNS OF INFECTION
Compendium February 2001
and FCV infections. FHV1
has been recognized as a cause
of ulcerative facial and nasal
dermatitis characterized histologically by necrosis, eosinophil
infiltration, and intranuclear
inclusion bodies, which can
mimic the eosinophilic granuloma complex and insect bite
hypersensitivity.23
Small Animal/Exotics 169
cellular necrosis, and severe
pancreatitis. A systemic vasculitis was suspected.
DIAGNOSIS
It is almost impossible to
make a diagnosis of FHV1 or
FCV infection based on clinical signs of URTD alone, although such signs as keratitis,
lameness, or severe oral ulceration may be more suggestive
Lameness and Pyrexia
Transient lameness and py- Figure 2—Severe lymphoplasmacytic stomatitis and fauci- of one virus or the other
rexia with or without concur- tis. Feline calicivirus was isolated from an oropharyngeal (Table I). Mixed infections
may also occur, further comrent oral or respiratory signs swab.
plicating the diagnosis. Vaccihave been reported in associanation history cannot be used
tion with acute FCV infection
to aid diagnosis because the
and after FCV vaccination.
vaccines do not prevent infecThese signs appear to be assotion or clinical signs. A hisciated with localization of
tory of recurrent bouts of
virus and/or immune comdisease, especially when complexes in the joints.24
bined with stressful events,
can be suggestive of FHV1
Reproductive and
infection. When conjunctiviPerinatal Disease
tis is present, chlamydiosis
Feline herpesvirus-1 may cause
should be excluded through
severe disease in kittens. Neoappropriate testing or treatnatal mortalities of up to 60%
have been reported.25 Ocular Figure 3—Ocular discharge in a kitten infected with feline ment with doxycycline for 3
discharges may be so severe that herpesvirus-1. (Courtesy of Robert Larocca, DVM, Uni- weeks. Collection of nasal or
oropharyngeal swabs for isokittens’ eyes may not open (Fig- versity of Minnesota)
lation of B. bronchiseptica
ure 3). Pregnant cats infected
with FHV1 may abort, resorb fetuses, or give birth to
should be considered. The presence of epistaxis, unilatcongenitally affected kittens. Attempts to isolate FHV1
eral nasal discharge, facial deformity, fundic abnormalifrom the reproductive tract have yielded mixed results,
ties, or marked submandibular lymphadenopathy
and it is unclear whether abortion is secondary to the
should prompt a search for other causes of URTD (e.g.,
nonspecific debilitating effects of FHV1 infection or
malignant neoplasia, nasopharyngeal polyps, coaguresults from infection of the reproductive tract.25 Using
lopathy, foreign bodies, dental disease, fungal infection).29
PCR, I have detected FHV1 DNA in vaginal swabs
from two cats with reproductive disease. FCV has rarely
The most reliable microbiologic assay is virus isolabeen associated with abortion in cats.26
tion from nasal, conjunctival, and/or oropharyngeal
swabs after inoculation of cell monolayers grown in the
Other Clinical Signs
laboratory. Oropharyngeal swabs are more likely to
yield a diagnosis than are conjunctival swabs, and virus
Feline calicivirus has also been associated with enterimust be viable for detection. The fragile envelope of
tis and feline lower urinary tract disease,27 but its role in
these syndromes is not clear. A highly virulent strain of
FHV1 may be destroyed while transporting and storing
FCV was recently isolated from an outbreak of a sysswabs, decreasing its infectivity for cell culture; FCV is
temic hemorrhagic-like fever.28 The condition was charmore resistant to destruction than is FHV1. Therefore,
swabs should be transported on ice in a viral transport
acterized by high mortality, fever, anorexia, ulcerative
medium containing antibiotics to prevent bacterial
facial dermatitis, and diffuse cutaneous edema. Several
overgrowth. Rose Bengal stain should not be applied
cats developed coagulopathy along with hypoproteinebefore sample collection because of its light-dependent
mia and mild hyperbilirubinemia. Necropsy findings
antiviral properties. Virus isolation is time-consuming
included pneumonia, intestinal crypt necrosis, hepatoDETECTING VIRUS ■ UNCOMMON SIGNS ■ MICROBIOLOGIC ASSAYS
170 Small Animal/Exotics
Compendium February 2001
and can be expensive for large numbers of samples. Because FCV tends to grow more rapidly in culture, its
presence in a sample can prevent identification of concurrent FHV1 infection, especially when confirmatory
immunofluorescent antibody staining of cell monolayers is not conducted.
Application of fluorescent antibody by direct or indirect techniques to cytology slides has commonly been
used to diagnose FHV1 and FCV infections but is less
sensitive than is virus isolation and may be associated
with false-positive results because of nonspecific fluorescing debris. Prior staining of eyes with fluorescein
may also produce false-positive findings.30
Although development of the ELISA has improved
the sensitivity of serologic tests for FHV1 and FCV,14
serology is not recommended for routine diagnosis of
respiratory viral infections. Acute and convalescent
phase samples must be taken 1 to 2 weeks apart for a
retrospective diagnosis. Titers induced by vaccination
can confound diagnosis. Because titers for FHV1 tend
to remain constant in cats with chronic low-grade infections, the paired sera approach loses its value. For
cats with FCV, titers can vary, depending on the degree
of homology between the infecting virus and the antigen used in the assay.
Amplification of viral DNA fragments using PCR is
rapid, exquisitely sensitive, and increasingly available
for the detection of FHV1. Development of diagnostic
PCR assays for FCV has been slow because of the difficulty in designing assays that amplify nucleic acid from
a variety of strains and susceptibility of RNA to degradation. The detection limit of reported assays for
FHV1 has ranged from 30 to millions of copies of the
FHV1 genome, with sensitivities 25% to 80% higher
than those of virus isolation.7,31,32 PCR may be particularly sensitive for detection of FHV1 in vaccinated cats
or during reactivation, when the presence of antibody
renders the virus uncultivatable. Concern has been
TABLE I
Features of Feline Herpesvirus-1 and Feline Calicivirus Infections
that Influence Diagnosis, Prognosis, and Management
Feature
FHV1
FCV
Implications
Clinical signs
Keratitis, corneal
ulceration
Lymphoplasmacytic,
stomatitis, severe oral
ulceration, lameness
If present, these signs aid in
making a diagnosis (mixed
infections may occur)
Environmental survival
<18 hours
<10 days
Resting areas for 24 hours may
destroy FHV1 but not FCV; poor
specimen handling of culture is
more likely to affect diagnosis of
FHV1 than that of FCV
Disinfectant susceptibility
Most common
disinfectants
Iodine, hypochlorite,
and glutaraldehyde
but not QUATs,
anionic detergents,
and ethanol
Use of such disinfectants
as QUATs does not inactivate
FCV in the environment
Chronic shedding pattern
Virus is shed
intermittently;
may be induced
by stress
Virus is shed
continuously;
level of shedding
is not affected by
stress
FCV can be detected more
readily in carrier cats than
can be FHV1; history of
intermittent signs, especially
after stress, suggests FHV1
infection; FCV may be more
of a threat to susceptible cats;
minimizing stress only reduces
shedding of FHV1
Duration of carrier state
Lifelong
Variable; most
cats eliminate
FCV within months
to years
May influence prognosis
for cats with chronic or
recurrent disease
FCV = Feline calicivirus; FHV1 = feline herpesvirus-1; QUAT = quaternary ammonium compound.
DIAGNOSTIC STAINS ■ SEROLOGIC TESTS ■ POLYMERASE CHAIN REACTION
Compendium February 2001
Small Animal/Exotics 171
raised that highly sensitive assays, particularly those involving nested PCR, may detect asymptomatic shedding or shedding of vaccine virus rather than that associated with disease. Some suggest the use of nested
PCR be minimized for routine diagnosis.33 False-positive results associated with contamination can occur
during sample collection or in the laboratory and thus
can be particularly problematic with such assays.
Regardless of the method used to detect the organism, results must always be interpreted in light of the
history and clinical signs because viral shedding is not
always accompanied by clinical signs. Chronic infections involving immune-mediated complications may
be associated with undetectable levels of virus, regardless of the test used. The prevalence of FHV1 infection
is much lower in cats with chronic disease than in cats
with acute disease.34 Nevertheless, attempts to obtain a
diagnosis are encouraged. Knowledge of causative organism(s) has prognostic value and can aid management strategies, especially in chronic cases and when
multiple cats are involved (Table I).
TREATMENT
Treatment is primarily symptomatic. Broad-spectrum
antimicrobials, fluid and nutritional support, nursing
care, and airway humidification should be considered.
The macrolide azithromycin has been a popular choice
for antimicrobial treatment, partly because of its efficacy in human chlamydial infections. Other antibiotics
(e.g., oral amoxicillin 22 mg/kg every 12 hours; oral
doxycycline 5 mg/kg every 12 hours) are effective
against secondary bacterial infection and preferred to
avoid development of resistance to the new macrolides.
C. felis and B. bronchiseptica are also sensitive to doxycycline; however, in one study, doxycycline failed to
eliminate shedding of B. bronchiseptica from experimentally infected cats after clinical recovery.35
Controlled, blinded, and randomized studies assessing
the efficacy of antivirals in cats with chronic respiratory
viral infections are needed, and experience is anecdotal.
Topical antiviral preparations (e.g., trifluridine, idoxuridine) are available for FHV1-induced keratitis and,
when applied frequently, may help minimize viral replication. These synthetic nucleosides incorporate into
viral nucleic acid and inhibit the enzymes of DNA synthesis. Toxic side effects, including hepatopathy (associated with trifluridine), leukopenia, and gastrointestinal
disease (associated with idoxuridine), occur when these
drugs are given systemically. Because corneal irritation
can occur, these drugs should be used with caution.
Idoxuridine, which can be obtained from a compounding pharmacy as a 0.1% solution or 0.5% ointment, is
less efficacious than is trifluridine in vitro36 but is also
less irritating and less expensive. Some ophthalmologists
have suggested topical application of dilute povidone–
iodine solution as a safe and inexpensive alternative. LLysine and oral and topical recombinant human α-interferon have also been used for refractory FHV1 infec-
TABLE II
Drugs Used to Treat Refractory Feline Herpesvirus-1 Infections and Feline Herpesvirus-1–Induced Keratitis
Drug
Route of Administration
Dose Schedule
Comments
Idoxuridine (0.1%)
Topical ophthalmic
1 drop every 2 hours for
first 2 days, then every
4 to 6 hours
May be less efficacious than is
trifluridine but less irritating
and less expensive
Trifluridine (1%)
Topical ophthalmic
1 drop every 2 hours
for first 2 days,
then every 4 to 6 hours
Very expensive; most
efficacious in vitro
Povidone–iodine solution
(0.3% in normal saline)
Topical ophthalmic
1 drop every 4 to 6 hours
Inexpensive, safe; efficacy
unknown
L-Lysine
Oral
250 mg every 12 hours
(adults) or once daily
(kittens)
No reported adverse effects;
efficacy unknown
α-Interferon
Oral; topical
ophthalmic/intranasal
30 U once daily; 1 drop
of 30–50 U/ml solution
in artificial tears once
daily
No reported adverse effects;
efficacy unknown
INTERPRETING TEST RESULTS ■ ANTIMICROBIALS ■ TOXIC SIDE EFFECTS
172 Small Animal/Exotics
Compendium February 2001
tions. Neither have been associated with adverse effects,
but their efficacy is unknown. Recombinant α-interferon is degraded by proteolytic enzymes before it can be
absorbed, but there may be some absorption by the upper gastrointestinal mucosa. Stimulation of oral lymphatic tissue has also been suggested as a mechanism of
action.37 Drug doses are listed in Table II.
Response to treatment is often poor. The purine nucleoside acyclovir has been used; but FHV1 is relatively
resistant to this drug, and severe toxicity may occur in
cats when therapeutic blood levels are achieved. One
study that evaluated valacyclovir, which undergoes
rapid first-pass hepatic metabolism to acyclovir and Lvaline, was prematurely terminated because of the development of severe renal, hepatic, and bone marrow
toxicity in treated cats.38 Use of topical corticosteroids
in cats with ocular complications of FHV1 infection is
controversial because of the risk for reactivation, worsening of infection, and ulcerative keratitis.
CONTROL
In catteries, preventing the spread of FHV1 and FCV
is very important. Elimination of infection is virtually
impossible because of the carrier state. Even when latent FHV1 carriers were identified and culled after inducing shedding with corticosteroids, eradication was
not achieved.25 Transmission is reduced by regular disinfection (1:32 bleach:detergent solution), optimal environmental temperature, low relative humidity, and
adequate ventilation. Proper quarantine and testing
procedures can minimize introduction of the viruses
into breeding colonies.39–41
Vaccination does not protect against infection from
incoming carrier cats or prevent a cat from becoming a
carrier. Modified-live virus vaccine may establish a persistent infection. However, vaccination can reduce disease severity and may shorten the duration of shedding,
reducing environmental contamination. Modified-live
systemic vaccines probably provide the longest duration
of immunity. Signs of URTD may result in cats that inhale an aerosol created during parenteral vaccination or
lick the injection site. Killed vaccines do not have the
risk of postvaccinal signs of URTD and are the vaccine
of choice for pregnant and immunosuppressed cats;
their protective effect may last several years.42 Two doses of a parenteral vaccine given 3 to 4 weeks apart are
generally required for adequate protection. Intranasal
vaccines are useful against outbreaks in catteries because they provide rapid immunity despite maternal
antibodies. Protection may be achieved within 2 to 4
days. Mild to moderate sneezing and ocular discharge
often occur within 4 to 7 days after vaccination. Intranasal vaccines were previously believed to protect
TREATMENT RESPONSE ■ VACCINATION RECOMMENDATIONS
174 Small Animal/Exotics
against latency, but this has recently been disproved.8
There is some concern that vaccine pressure may have
led to selection of FCV strains that have poor cross-reactivity with the vaccine strain F9. Incorporating additional FCV strains into vaccines has been proposed.43
Because of the potential risks associated with vaccination, including vaccine-induced fibrosarcomas and induction of immune-mediated disease, as well as evidence suggesting a duration of immunity of more than
3 years after vaccination of cats with inactivated vaccines, the American Association of Feline Practitioners
and the Academy of Feline Medicine have published
general recommendations that cats undergo a booster 1
year after the primary course, then every 3 years.44 Nevertheless, the frequency of booster administration remains controversial; and immunization recommendations should be based on the specific lifestyle and
history of each cat. Thus some authors have recommended annual boosters for outdoor cats, whereas triennial boosters may be sufficient for those living indoors.37
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About the Author
Dr. Sykes is affiliated with the Department of Small Animal Clinical Sciences, College of Veterinary Medicine,
University of Minnesota, St. Paul.
ARTICLE #4 CE TEST
The article you have read qualifies for 1.5 contact hours of Continuing Education Credit from
the Auburn University College of Veterinary
Medicine. Choose only the one best answer to each
of the following questions; then mark your answers on the test form inserted in Compendium.
CE
1. Which of the following statements best reflects survival of FCV and FHV1 in the environment?
a. FHV1 is more resistant than is FCV and survives up
to 1 week in the environment.
Small Animal/Exotics 175
b. FCV is more resistant than is FHV1 and survives up
to 2 years in the environment.
c. FHV1 is more resistant than is FCV but is susceptible to quaternary ammonium compounds.
d. FCV is more resistant than is FHV1, and quaternary ammonium compounds are poorly effective.
e. FHV1 is more resistant than is FCV, and hypochlorite is required to inactivate it.
2. Approximately 2 months after infection, what proportion of cats are carriers of FHV1 and FCV?
a. approximately 50% and 100%, respectively
b. All cats infected with both FHV1 and FCV become carriers.
c. approximately 80% to 100% and 5%, respectively
d. approximately 5% and 50%, respectively
e. approximately 80% to 100% and 50%, respectively
3. Which of the following has not been shown to be a
site of latency for FHV1?
a. trigeminal ganglia
b. cornea
c. submandibular lymph node
d. tonsil
e. nasal turbinate
4. Shedding of FCV in carrier cats is
a. intermittent and associated with stress or corticosteroid use.
b. continuous for the rest of the cat’s life.
c. intermittent and not associated with stress or corticosteroid use.
d. continuous for a variable period.
e. intermittent in some cats and continuous in others.
5. Which clinical manifestation(s) is more likely to occur
in FCV-infected cats than in FHV1-infected cats?
a. keratitis and corneal ulceration
b. abortion
c. lameness
d. high neonatal mortality
e. ulcerative facial and nasal dermatitis, with eosinophil infiltration
6. Currently, antemortem diagnosis of FCV infection is
best obtained using which of the following assays?
a. PCR
b. serum neutralization
c. application of fluorescent antibody to smear preparations of affected tissue
d. cell culture
e. reverse transcription PCR
7. Which of the following is the first-choice treatment of
acute FHV1 infection?
a. trifluridine because it is the most effective antiviral
drug for treating FHV1
b. idoxuridine because it has fewer side effects than
does trifluridine
176 Small Animal/Exotics
c. acyclovir because it is effective when given systemically and has minimal side effects
d. human recombinant α-interferon because it is safe
and has been shown to be effective against FHV1
infection when given topically and systemically
e. no specific treatment only supportive therapy
8. Which of the following is not a feature of intranasal
FHV1 and FCV vaccines?
a. protection despite maternal antibody
b. failure to protect against latent FHV1 infection
c. establishment of latent FHV1 infection by the vaccine virus
d. slow onset of immunity
e. postvaccinal sneezing and ocular discharge
9. Chronic ocular infections associated with FHV1 may
be difficult to diagnose because
a. the virus is located in deep tissue that is inaccessible
using swabbing techniques.
Compendium February 2001
b. immune-mediated disease predominates.
c. the virus is present in an altered form that does not
replicate well in cell culture.
d. antibody complexing with virus prevents its replication in cell culture.
e. multiple strains of FHV1 form as a result of immune pressure and are not reliably detectable using
PCR.
10. Which of the following is not an advantage of PCR
for diagnosing FHV1 infection?
a. False-positive results do not occur.
b. Sensitivity is greater than that of culture.
c. FHV1 need not be viable for detection; therefore
special transport media are not required.
d. Rapid turnaround time is possible.
e. Latent virus can be rapidly detected in the tissue of
infected cats.