Since January 2020 Elsevier has created a COVID-19 resource centre with

free information in English and Mandarin on the novel coronavirus COVID-

19. The COVID-19 resource centre is hosted on Elsevier Connect, the
company's public news and information website.

Elsevier hereby grants permission to make all its COVID-19-related

research that is available on the COVID-19 resource centre - including this
research content - immediately available in PubMed Central and other
publicly funded repositories, such as the WHO COVID database with rights
for unrestricted research re-use and analyses in any form or by any means
with acknowledgement of the original source. These permissions are
granted for free by Elsevier for as long as the COVID-19 resource centre
remains active.
 PART FIVE

Disorders of the
Respiratory Tract:
A. Nasal Cavity and Sinuses

CHAPTER 35

Feline Viral Upper

Respiratory Disease
Alan D. Radford • Rosalind M. Gaskell • Susan Dawson

Definition creasing evidence that Bordetella bronchiseptica is an im-

portant cause of respiratory disease in cats. Chlamydophila
Feline calicivirus (FCV) and feline herpesvirus (FeHV, felis (previously Chlamydia psittaci var felis) may also
also called feline rhinotracheitis virus) remain the two cause respiratory disease, although it is predominantly
major causes of infectious upper respiratory tract disease associated with conjunctivitis. Other agents that have also
in cats. Despite the widespread use of vaccines over been associated with feline respiratory disease include
some 30 years, respiratory disease caused by these two feline reovirus, cowpox virus, and various bacteria and
viruses remains a significant clinical problem. In gen- mycoplasmas.
eral, the disease is most commonly seen where cats are
grouped together (e.g., in boarding catteries or breeding
establishments), particularly in young kittens as they
lose their maternally-derived antibody.
Etiology
When considering a case of apparently infectious respi-
FELINE CALICIVIRUS
ratory disease in cats, it is important to remember that
other pathogens may be involved, and it may be appropri- Feline calicivirus is a small, nonenveloped, single-stranded
ate to include diagnostic testing for these as part of a di- RNA virus belonging to the Caliciviridae. This virus family
agnostic work-up. In addition to FCV and FeHV, there is in- contains a large number of important pathogens of man
271
272 PART FIVE — Disorders of the Respiratory Tract: A. Nasal Cavity and Sinuses

and animals including the Norwalk-like and Sapporo-like pears to be the main host for FeHV, isolates have also
viruses (both important causes of diarrhea in man and been obtained from nondomestic felids such as cheetahs.
other animals) and rabbit hemorrhagic disease virus (a When compared with the variability that is a feature
generally fatal disease of rabbits). However, the viruses of FCV, FeHV isolates are generally much more similar to
most closely related to FCV are vesicular exanthema of one another. Slight differences between some biotypes
swine virus (no longer isolated), San Miguel sea lion virus, do exist, however, with some attenuated strains used in
and canine calicivirus (CaCV). These have been grouped vaccines and some apparently more virulent challenge
together in the vesivirus genus, reflecting a general ability strains. Antigenically, all isolates of FeHV are very simi-
of viruses in this genus to induce vesicles as a prominent lar and belong to one serotype. The virus also appears
part of their pathology. relatively homogenous at the genetic level although
FCV infects both domestic cats and other members of some differences between isolates have been found.18-20
the Felidae.1,2 Although CaCV is genetically distinct from The overall homogeneity of feline herpesvirus means
FCV,3 other caliciviruses have also been detected in dogs there is currently no easy method to study the role of in-
that antigenically cross-react and genetically cluster with dividual isolates in the epidemiology of the disease.
FCV.3-5 This raises the possibility that dogs may be infected
by FCV-like viruses, and that if they are, these viruses may
be transmitted between dogs and cats. However, the sig-
nificance of these canine FCV-like viruses to either dogs or
Pathogenesis and Pathology
cats remains largely uncertain.
FELINE CALICIVIRUS INFECTION
When the genetic sequences of different FCV isolates
are compared with each other, they show a considerable Cats can be infected with FCV via the nasal, oral, or con-
amount of variability. This heterogeneity is often a fea- junctival routes. The virus replicates mainly in the oral
ture of RNA viruses and is a reflection of the low accu- and respiratory tissues, although some strains vary in
racy or fidelity of the viral encoded polymerase. This their tissue tropism and pathogenicity. Thus some have
leads to plasticity of the viral genome and the potential a predilection for the lung and others have been found
to generate variants at relatively rapid rates in compari- within macrophages in the synovial membrane of
son with organisms whose genetic material is based on joints.21,22 Virus has also been found in visceral tissues;
DNA. Despite the observed variability of FCVs, compar- feces; and, occasionally, in urine. The significance of this
ative genetic analysis has failed to separate isolates of in transmission is unknown but is likely to be minimal.
FCV into distinct clusters or genogroups. There appears Perhaps the most consistent pathological feature of
to be no clear correlation between the sequence of a FCV infection is oral ulceration. These ulcers begin as
virus and either its year or location of isolation, or with vesicles that subsequently rupture, with necrosis of the
the particular disease with which it is associated.6-10 The overlying epithelium and infiltration of neutrophils at
genetic diversity of FCV has been used to develop typing the periphery and base. Healing generally takes place
methods based largely on sequence analysis to differen- over a period of 2 to 3 weeks. Pulmonary lesions occur
tiate between isolates. These methods have been used to more rarely and appear to result from an initial focal
explore the epidemiology of FCV-related disease and the alveolitis, leading to areas of acute exudative pneumonia
role of live vaccine virus in disease in recently vacci- and then to the development of a proliferative, intersti-
nated animals.11-13 tial pneumonia. Although primary interstitial pneumo-
This variability of the FCV genome has important im- nia may occur with FCV, especially with the more viru-
plications to the antigenicity of this virus. The sequence lent strains, it is possible that its importance in natural
variability has been shown to be particularly pronounced cases of disease has been overemphasized in the past.
in key regions of the capsid protein that are responsible This is because many early experimental studies used
for the antigenic structure of the virus. It is therefore per- aerosol challenge to infect cats, rather than the more nat-
haps not surprising that most strains of FCV can be dis- ural oronasal route of infection. Lesions seen in FCV-in-
tinguished from one another on the basis of their anti- fected joints consist of an acute synovitis with thicken-
genicity. However, there is sufficient cross-reactivity ing of the synovial membrane and an increase in
between FCV strains to allow them to be grouped to- quantity of synovial fluid within the joint.22
gether in a single serotype and to allow some degree of
cross-protection between the majority of strains. This has
FELINE HERPESVIRUS INFECTION
important implications in relation to vaccine design.
As with FCV, cats are infected with FeHV by nasal, oral,
FELINE HERPESVIRUS or conjunctival exposure. The virus primarily targets a
number of tissues in the upper respiratory tract includ-
Feline herpesvirus is a member of the herpesvirus family ing the soft palate; tonsils; turbinates; conjunctivae; and,
and has a double-stranded DNA genome with a glycopro- sometimes, the trachea. Virus shedding occurs as early
tein-lipid envelope. It is classified in the alphaherpesvirus as 24 hours after infection and generally persists for 1 to
subfamily, which contains most of the herpesviruses of 3 weeks. Although it appears to be a rare sequel to in-
veterinary interest and is very closely related genetically fection, viremia has been reported, and generalized dis-
and antigenically to canine herpesvirus-1 and phocine ease can be seen, particularly in young kittens or im-
(seal) herpesvirus-1.14-17 Although the domestic cat ap- munosuppressed individuals.
 CHAPTER 35 — Feline Viral Upper Respiratory Disease 273

Infection with FeHV leads to areas of multifocal ep-

ithelial necrosis with neutrophilic infiltration and fibrin
exudation. Intranuclear inclusion bodies are present in
infected cells. Replication of the virus can also lead to
osteolytic changes in the turbinate bones. Acute lesions
normally take between 2 and 3 weeks to resolve, al-
though turbinate destruction may be permanent and
may predispose affected cats to chronic rhinitis. Primary
lung involvement may occur but as with FCV infection,
is rare. Although disease is not dependent on the pres-
ence of other organisms, secondary bacterial infection
can enhance the pathology leading to bacterial pneumo-
nia and sinusitis.

Clinical Signs
The clinical signs following infection with FCV or FeHV
depend on a number of factors including those associ-
ated with the agent (e.g., strain and infecting dose), and Figure 35-1. Two lingual ulcers on the margins of the tongue of
those associated with the host (e.g., general health, age, a cat acutely infected with FCV.
and genetic make-up). Differences in microbial flora, in
husbandry conditions, and the presence of any preexist-
ing immunity may also affect the course of infection.
Concurrent infections with immunosuppressive viruses not be associated with respiratory disease.22,28,29 The
such as feline immunodeficiency virus and feline lameness is usually described as shifting, affecting more
leukemia virus may lead to more severe disease.23-25 than one leg, and is often accompanied by pyrexia.
Affected cats are often dull and anorexic. Most cases re-
cover within 1 to 2 days, and there are no known long-
FELINE CALICIVIRUS
term effects on the joints. It is likely that such cases of
Following a short incubation period of 2 to 5 days, early lameness and the more typical cases associated with res-
signs of infection with most strains of FCV include de- piratory disease are not entirely distinct clinical entities.
pression and pyrexia. Affected cats generally appear Instead, it has been suggested that most “limping”
brighter than those infected with FeHV. Perhaps the most strains of FCV may cause some degree of respiratory dis-
characteristic clinical sign associated with FCV infection ease, and vice versa.29
is ulceration of the tongue (Figure 35-1). Ulcers may also Lameness associated with FCV infection has also been
occasionally be seen on the lips or the nose. Cats with ul- seen after vaccination.30-32 Sequence analysis of virus iso-
cerated mouths may show excessive salivation with wet- lated from affected cats has shown that in most cases, the
ness around the mouth. However, affected cats often lameness appears to be caused by coincidental infection
show few other clinical signs, and it is likely that many with field virus in young kittens as they lose their mater-
cases in which oral ulceration is the main or only clinical nally-derived antibody. However, in some cases, virus
sign go unrecognized. Sneezing, conjunctivitis, and ocu- originating from live vaccines appears to be involved.11,12
lar and nasal discharges typically occur but are usually A potential worrying clinical development in the
less prominent than following FeHV infection. In most repertoire of FCV induced disease has recently been re-
typical cases, clinical signs resolve over 7 to 10 days. ported in the United States. In 1998, the first of several
As well as this typically mild oral and respiratory dis- outbreaks of disease was described in which affected
ease, a wide range of other clinical presentations may cats presented variably with facial and paw edema
also be observed following FCV infection. This patho- (50%), pyrexia (90%), upper respiratory tract infection
genic variability is again likely to be a reflection of the (50%), icterus (20%), and hemorrhage from the nose
genetic variability of this virus. Therefore, although most and in the feces (30% to 40%).9 Necrosis with ulceration
strains induce fairly mild disease, some appear to be was also seen in areas of earlier edema. The mortality
nonpathogenic, whereas others are capable of inducing rate associated with infection often reached 50%, with
more severe disease. both kittens and adults succumbing to infection.
Skin ulceration on other parts of the body may be Necropsy findings included pneumonia (80%), he-
seen but occurs rarely and is generally mild. Some of the patomegaly (50%), pancreatitis (10%), and pericarditis
more virulent strains of FCV may cause pneumonia with (10%). The disease has been recreated experimentally
associated dyspnea, particularly in younger animals by infection with FCV isolated from affected cats, further
when the disease becomes much more serious. FCV has confirming the role of FCV in this serious disease. The
also been reported in occasional cases of abortion.26,27 variability of FCV means we should perhaps not be sur-
An acute lameness and pyrexia syndrome has also prised by the occasional new and distinct manifestation
been described following FCV infection; it may or may of clinical disease. To date, most of these outbreaks have
274 PART FIVE — Disorders of the Respiratory Tract: A. Nasal Cavity and Sinuses

been relatively well controlled with strict quarantine and

disinfection.
The chronic oral disease lymphoplasmacytic gingivitis
stomatitis complex (LPGS) has also been associated with
FCV infection. In some studies, approximately 80% of
cats with LPGS have been shedding FCV, compared with
20% of controls.33,34 However, these shedding rates may
depend on the criteria used for the selection of clinical
cases.35 Chronic stomatitis developed following the acci-
dental introduction of FCV into one cat colony, further
suggesting a role for FCV in this disease.36 However,
chronic oral disease has not been reproduced experi-
mentally in cats,23,37-39 and attempts to identify consistent
differences between FCV isolates from cats with LPGS
and those from cats with other FCV-associated diseases
have so far been unsuccessful.6,7,39 It is therefore likely
that factors not associated with FCV, including other
pathogens and host factors, may also play a role in this
complex and serious syndrome. Figure 35-2. A kitten with early FeHV infection showing marked
There has also been some debate about the role of serous ocular and nasal discharges.
FCV in feline urinary tract disease. Although virus can
be visualized in and isolated from urine, there are cur-
rently no studies demonstrating a clear association be- cases of abortion were seen, even in severely affected
tween infection and disease.8 pregnant queens.47
As with classic FCV infection, the mortality rate with
FELINE HERPESVIRUS FeHV infection is generally low. In very young kittens or
immunosuppressed cats, the mortality rate may be
FeHV infection generally causes more consistent and se- higher because of secondary bacterial infections and,
vere upper respiratory and conjunctival disease than more rarely, generalized viral infection. Clinical signs
FCV, particularly in younger susceptible animals. The in- generally resolve over a period of 2 to 3 weeks. However,
cubation period is usually 2 to 6 days but may vary de- in some animals, permanent damage of the mucosa and
pending on the challenge dose, with a higher dose in- turbinates may occur, leaving affected cats prone to
ducing more rapid and severe clinical signs. chronic upper respiratory bacterial infections of the
Initially, infected cats develop depression, marked nose, paranasal sinuses, and conjunctiva.
sneezing, inappetence, pyrexia, and serous ocular and
nasal discharges (Figure 35-2). In the earlier stages of in-
fection, cats may also show excessive salivation and Diagnosis
ptyalism (drooling of saliva). Conjunctivitis typically de-
velops, and the ocular and nasal discharges change from In many individual cases, it may not be necessary to de-
serous to mucopurulent. In severe cases, dyspnea and termine the precise cause of infectious upper respiratory
coughing may also occur. Although oral ulceration can tract disease. However, there are some circumstances
occur with FeHV infection, it is relatively rare compared where a diagnosis is advisable. These include outbreaks
with that following FCV infection. Occasionally, primary of disease in colonies, where specific control measures
viral pneumonia or generalized disease may occur, par- may be required; and disease in vaccinated cats, where
ticularly in young or debilitated animals. Other manifes- questions may arise concerning the safety and efficacy of
tations of infection include ocular disease such as ulcer- a vaccine.
ative or interstitial keratitis and a possible association Whereas many of the clinical signs that occur in viral
with uveitis.40 Improved diagnosis (e.g., using the poly- upper respiratory disease are common to both FCV and
merase chain reaction) has led to greater recognition of FeHV infection, a presumptive diagnosis in some cases
such conditions.41-43 Skin ulcers and dermatitis syndrome may be possible based on clinical signs alone. FCV tends
in domestic cats and cheetahs,44-46 and neurological signs to cause a relatively mild disease in which oral ulcera-
have also been reported, but these are likely to be rare tion is a relatively consistent feature. Lameness, if pres-
sequels to FeHV infection. ent, particularly in young kittens, is also suggestive of
Unlike many other alphaherpesviruses (e.g., canine FCV infection. In contrast, FeHV tends to cause a more
herpesvirus-1), FeHV does not appear to have a signif- consistent and severe disease than FCV, associated with
icant role in reproductive tract disease. Experimental copious ocular and nasal discharges and sneezing.
studies have suggested that abortion, when it occa- Laboratory diagnosis is necessary where a definitive
sionally occurs, is caused by the severe systemic na- diagnosis is required. For both viruses, this has classi-
ture of the illness rather than being a direct effect of cally involved virus isolation in feline cell cultures. A
the virus itself. Indeed, in an investigation of a natural plain oropharyngeal swab is taken from the cat and
outbreak of FeHV in specific pathogen-free cats, no placed into suitable viral transport medium, then sent
 CHAPTER 35 — Feline Viral Upper Respiratory Disease 275

within 24 hours to an appropriate laboratory. For viral regular cleansing of discharges, is essential. The cat
culture, results may take up to 2 weeks to confirm, par- should be encouraged to eat by offering strongly flavored,
ticularly if the result is that no virus is isolated. Serology aromatic foods. If eating is painful, liquidized or special-
is generally not helpful for the diagnosis of acute FCV or ized proprietary foods may be of some help. In some
FeHV infection because of widespread immunity from cases, the use of appetite stimulants such as diazepam or
vaccination or earlier infection. The polymerase chain cyproheptadine may also be of some benefit. Some se-
reaction (PCR) is also increasingly being used for the di- verely affected cases may require fluid therapy, and where
agnosis of FeHV.48-53 PCR and sequencing has also been anorexia is prolonged, a nasogastric esophagostomy or
used to distinguish between FCV isolates, where it has gastrostomy tube may be indicated.59 In cases of chronic
been particularly useful in the investigation of vaccine rhinitis, mucolytic drugs such as bromhexine hydrochlo-
failures11,12 and in dissecting the epidemiology of the dis- ride may help clear mucus from airways. However, con-
ease.54,55 The inherent variability of FCV strains has ventional steam inhalation (e.g., placing the cat in a
meant that the development of PCRs with high enough steamy room) is probably of as much use.
sensitivity to be used for the routine diagnosis of all FCV
strains has been very problematic. Whereas some PCRs
may show a high sensitivity with some strains, the sen- Epidemiology
sitivity is likely to be lower with others, in some cases
leading to false negative results. Recently, a real-time In the past, both FCV and FeHV were isolated from ap-
reverse-transcriptase PCR that targets relatively con- proximately equal numbers of cats with respiratory dis-
served regions of the virus genome has been described.56 ease. Recently, however, FCV appears to be isolated more
This method has been shown to be able to successfully commonly.60-62 This may be because of the antigenic di-
amplify a broad range of FCV strains detecting 100% of versity of FCV isolates compared with the single serotype
60 laboratory strains tested. of FeHV, which may affect the relative efficacy of the two
When diagnosing acute disease, results of virus isola- vaccines. Both viruses remain fairly widespread in the
tion must be interpreted with care. False positives may general cat population, with an increased prevalence
occur because of the presence of clinically normal carri- when cats are kept together. The viruses circulate and
ers in the population. False negatives may also occur maintain themselves in the cat population in one of three
particularly when only low levels of the infecting organ- ways. Firstly, there may be direct transmission of virus
ism are shed, such as may occur in the later stages of from acutely infected cats. Clearly, for the virus to persist
acute disease. Other infections, particularly Bordetella in this way, there must be a sufficient number of suscep-
bronchiseptica and Chlamydophila felis, may also be as- tible animals within the population and opportunities for
sociated with upper respiratory tract disease in the cat, contact between them. Secondly, because FCV (and, to a
and therefore it may be appropriate to include testing for lesser extent FeHV) can remain infectious for relatively
these as part of a diagnostic work-up. short periods outside a host, viral contamination of the
environment may lead to fomite transmission. This is
particularly relevant within the close confines of a cattery
Treatment or hospital, where secretions may contaminate cages,
feeding and cleaning utensils, or personnel.63 Finally, for
Currently no antiviral drugs are in widespread use for the both FCV and FeHV, animals that recover from acute dis-
treatment of FeHV or FCV. Drugs such as acyclovir, given ease may remain infected and develop persistent infec-
in human herpesvirus infection, do not seem to have tions. Despite vaccination, such carriers are common in
good activity against FeHV.57,58 However, antiviral treat- the population and are probably the main reason why
ments are available for topical use in cases of ulcerative these viruses remain so widespread.
keratitis associated with FeHV infection.43 Interferon has There are no known reservoir or alternative hosts for
been suggested to be useful for treatment of acute viral FeHV, and in utero transmission does not generally seem
infections. Some have advocated the use of human inter- to occur. The role of dogs in maintaining FCV in the pop-
feron orally, but the rationale for this is unclear because ulation is not known, although as stated previously, FCV-
the majority of orally administered interferon may be ex- like viruses have occasionally been recovered from dogs.
pected to be degraded in the stomach. Recently, a com-
mercial recombinant feline interferon has been licensed THE FCV CARRIER STATE
for parenteral administration in some countries, includ-
ing the United Kingdom. However, there is currently lit- Following acute infection with FCV, clinical signs gener-
tle documented evidence for its success in the treatment ally resolve in 7 to 10 days. However, most cats still shed
of feline upper respiratory infections. FCV in oropharyngeal secretions for 30 days after infec-
Broad-spectrum antibiotic treatment is generally rec- tion, and such cats are defined as carriers (Figure 35-3).
ommended in cases of viral respiratory disease to mini- Subsequently, experimental studies have suggested that
mize potential complications associated with secondary there is an exponential decline in the proportion of ani-
bacterial infection. Because swallowing may be painful, mals remaining infected, with approximately 50% of the
antibiotics can be given either as syrups (if available) or cats still shedding virus 75 days later.64 Although this
parenterally. In severe cases, bacterial culture and sensi- most likely represents an over-simplification of the true
tivity testing may be required. Good nursing care, with dynamics of the FCV carrier state, it is a useful guide.
276 PART FIVE — Disorders of the Respiratory Tract: A. Nasal Cavity and Sinuses

Infection Acute infection ⫹/⫺ disease

Shedding virus

Naïve susceptible
Not shedding virus

Vaccination or MDA
n
tio
ec
Inf

Infection

40% Colony cats

20% Show cats
5%-10% Household pets Carrier
Immune susceptible Clinically normal
Not shedding virus Shedding virus

Figure 35-3. FCV cycle of infection including the carrier state. Generally, clinically normal car-
riers develop following a period of acute clinical disease. However, carriers may develop in the
absence of previous clinical disease under protection from maternally- or vaccine-derived im-
munity. (Modified from Gaskell RM, Radford AD, Dawson S: Feline infectious respiratory dis-
ease. In Chandler EA, Gaskell CJ, Gaskell RM, editors: Feline medicine and therapeutics, ed 3,
Oxford, 2003, Blackwell Publishing.)

Individual FCV carriers may shed virus for life, but mune response.67,68 Such a process is common among
most cats appear to spontaneously eliminate the virus. RNA viruses that cause persistent infections and is asso-
The mechanism by which some cats clear infection is ciated with the low accuracy of virally-encoded RNA
not known. However, it is likely that in the field, rein- polymerases.
fection is common. Concurrent infections with other Despite the use of vaccines for approximately 30
pathogens may impact on the dynamics of the FCV car- years, the prevalence of FCV infection in the general cat
rier state. For example, there is some evidence that pre- population remains high. Before vaccines were intro-
existing FIV infection may potentiate FCV shedding ei- duced in the 1970s, surveys showed that approximately
ther in terms of the duration of shedding,23 or the titer 8% of household pets, 25% of cats attending cat shows,
of virus shed.25 and 40% of colony cats were shedding the virus.69
FCV carriers shed virus more-or-less continuously. However, in recent years, approximately 20% to 25% of
Individual cats seem to vary in the quantity of virus they cats in a variety of husbandry situations still shed
shed,65 and it is likely that those animals that shed the FCV.60,61,70 In one rescue shelter, FCV prevalence was ap-
higher amounts of virus will transmit infection most proximately 25% despite the regular use of vaccination
readily. In contrast, low-level shedders are probably not to control clinical disease.55 Molecular epidemiology
as infectious and may also be more difficult to detect be- studies showed that within this particular shelter, most
cause the level of virus shed may intermittently fall be- isolates were distinct, unless the isolates were obtained
low the sensitivity of virus diagnosis. Therefore when from cats that were housed in the same pen. This sug-
trying to detect FCV carriers, it is advisable to take a se- gests that the high prevalence within the rescue shelter
ries of swabs over several weeks before an individual is was because of the high prevalence of FCV in cats arriv-
believed to be FCV negative. ing at the shelter rather than significant transmission
The mechanism of persistence for FCV is not fully elu- within the shelter. In contrast, a single viral strain often
cidated. Viruses recovered from carrier cats have been seems to predominate in household colonies with a high
shown to change antigenically over time.66,67 This anti- prevalence of infection, although evolution of the indi-
genic evolution correlates with sequence changes in key vidual colony isolates may occur over time.71 Molecular
antigenic domains of the virus capsid, and has led to the studies should enable a clearer understanding of the epi-
suggestion that antigenic variants generated within car- demiology of FCV and the role of the carrier state in the
riers allow FCV to escape neutralization by the cat’s im- continued high prevalence of this virus.
 CHAPTER 35 — Feline Viral Upper Respiratory Disease 277

Variable period
n
tio
ina DA

In
fe
c c

ct
Va or M

io
Immune susceptible

n
Not shedding virus

Infection 2-3 Weeks

CARRIER ⫹/⫺ stress

Latently infected
Susceptible cat Acute infection Clinically normal
Clinical disease Not shedding virus
Shedding virus

Shed virus for Lag phase

1-13 days of 4-11 days

Reactivation
⫹/⫺ disease
Shedding virus

Figure 35-4. FeHV cycle of infection including latency. Generally, latently infected carriers de-
velop following a period of acute clinical disease. However, latency may also develop in the ab-
sence of previous clinical disease under protection from maternally or vaccine-derived immunity.
(Modified from Gaskell RM, Radford AD, Dawson S: Feline infectious respiratory disease. In
Chandler EA, Gaskell CJ, Gaskell RM, editors: Feline medicine and therapeutics, ed 3, Oxford,
2003, Blackwell Publishing.)

Preexisting immunity, acquired either naturally as to 2 weeks. Thus carrier cats are most likely to be infec-
maternally derived antibody or artificially following par- tious from 1 to 3 weeks following a stress (see Figure
enteral vaccination, does not prevent infection with FCV. 35-4). Corticosteroid treatment can also induce shedding,
Animals may become carriers following subclinical in- and care should be taken when using these drugs in carri-
fection with field virus, thereby maintaining infection in ers because some of these cats may develop severe re-
the population (see Figure 35-3). There is no evidence crudescent disease.
that vaccination will cure an existing carrier state. As with some other herpesvirus infections, FeHV re-
mains latent in carriers in trigeminal ganglia, although
THE FeHV CARRIER STATE there is evidence to show that other tissues may also be
involved.51,73,74 Latency is almost certainly lifelong, but
As with other alphaherpesviruses, cats become latently there is a refractory phase of several months after a pe-
infected with FeHV following acute disease (Figure 35-4). riod of shedding when animals are less likely to experi-
During latency, no infectious virus is detectable; how- ence another episode.
ever, periodical episodes of virus reactivation occur, dur- The importance of latent FeHV carriers lies in their
ing which times infectious virus is present in oronasal ability to transmit infection. Therefore any animal with
and ocular secretions. In some cases, carriers show mild a history of FeHV-associated respiratory disease, or with
clinical signs while they are shedding (recrudescence) persistent or recurrent signs, should be considered po-
which may act as a useful indicator that such individu- tentially infectious. Similarly any queen who repeatedly
als are likely to be infectious to other cats. produces litters that develop respiratory disease is prob-
Although latently infected carriers all have the potential ably a carrier and it may be advisable not to use such
to shed FeHV, some cats appear to do so more frequently, queens for breeding.
and as such are likely to be of greater epidemiological sig- As with FCV, immunity to FeHV, whether vaccine-in-
nificance. Reactivation may occur spontaneously but is duced or maternally-derived, does not prevent infection,
most likely to occur following a stress (e.g., after parturi- and cats may become carriers even though they have no
tion) or a change of housing (e.g., going into a boarding history of clinical disease (see Figure 35-4). In latently
cattery, to a cat show, or to stud).72 Shedding does not oc- infected queens, virus shedding that may be induced by
cur immediately after stress: there is a lag period of ap- the stress of parturition and lactation provides a source
proximately 1 week, followed by a shedding episode of up of infectious virus to kittens. Such a mechanism favors
278 PART FIVE — Disorders of the Respiratory Tract: A. Nasal Cavity and Sinuses

virus spread to the next generation without harming its Following primary infection with FeHV, most cats are
host. In the case of vaccination, there is no evidence that generally resistant to subsequent reinfection. However,
vaccination will eliminate an existing latent infection, al- protection is not necessarily complete in all animals and
though it is theoretically possible that it may reduce may only be of relatively short duration. By 6 months af-
episodes of virus shedding. ter infection, cats may only be partially protected from
subsequent challenge, and carrier cats may also develop
recrudescent disease. Low levels of virus neutralizing
Transmission antibody develop following initial infection or vaccina-
tion, suggesting that, as for other alphaherpesviruses,
FCV and FeHV are shed mainly in oral, nasal, and con- cell-mediated and local immunity play a significant role
junctival secretions in both acutely infected and carrier in protection. However, after reactivation or field virus
cats. Transmission mostly occurs by direct contact be- challenge, virus-neutralizing antibody titers generally
tween cats, but indirect transmission may occur. Thus rise to more moderate levels and thereafter remain rea-
cats may also be infected through contact with contam- sonably stable, independent of virus shedding episodes.
inated secretions on cages, feed bowls, cleaning utensils, Most cats are protected following the use of modified
and personnel.63 However, because both viruses are rel- live or inactivated FeHV vaccines. Again, however, im-
atively short-lived outside the cat, the environment is munity is not necessarily complete in all animals, even
not usually a long-term source of infection. if challenge takes place within 3 months of vaccina-
Unlike many respiratory pathogens in other species, tion.78,84,85 Similar levels of protection have been reported
true aerosol transmission is not thought to be of major after a year.86 More recent studies have shown that the
importance for the spread of feline respiratory viruses. relative efficacy of an inactivated vaccine decreased from
This is thought to reflect the small tidal volume of the cat 83% shortly after primary vaccination to 52% after
such that infectious aerosols are not generally produced 7.5 years.81
during normal respiration. However, macrodroplets pro- In kittens, maternally derived antibody (which is es-
duced by sneezing may travel over a distance of 1 to 2 sentially colostral) may persist for 10 to 14 weeks and 2
meters, allowing virus transmission to occur. to 10 weeks for FCV and FeHV, respectively.87,88 However,
Transmission is most successful in overcrowded condi- for both viruses, low levels of maternally derived anti-
tions where cats are more likely to have prolonged, close body do not necessarily protect against subclinical in-
contact. Poor ventilation and hygiene may also lead to a fection, and kittens infected at this time may become
build up of pathogens in the environment. Transmission carriers without showing clinical disease (see Figures
is thought to be more easily achieved from acutely in- 35-3 and 35-4).
fected cats rather than carriers, as discharges are more co-
pious and the amount of virus higher. However, carriers
are undoubtedly important sources of virus, particularly Prevention and Control
in transmission between queens and kittens, and in the
close contact seen between cats in multi-cat colonies. A number of vaccines against FCV and FeHV are avail-
able, and have been used relatively successfully for
many years. Nevertheless, because of the epidemiology
Immunity of the disease, respiratory disease may still occur, partic-
ularly where cats are housed together in breeding,
Most cats develop some degree of immunity to FCV fol- boarding, or rescue catteries. Therefore, prevention and
lowing natural infection; however, it may not always be control is best achieved by a combination of vaccination
complete or of long duration. In addition, the many dif- and cattery management.
ferent strains of FCV show varying degrees of cross-
protection. Immunity following the use of modified live or VACCINATION
inactivated vaccines is similarly incomplete, though this
may depend on the strains or challenge system used.75-78 The majority of vaccines marketed against FCV and
After vaccination, protection against FCV disease has FeHV are either live and attenuated or inactivated and
been reported to last for 10 to 12 months.79 More recent adjuvanted, and are licensed for parenteral administra-
work has suggested that partial protection may last con- tion. Modified live intranasal vaccines are also marketed
siderably longer. Moderate levels of virus neutralizing in some countries, including the United States.
antibody have been shown to persist in a group of vac- Most vaccines induce reasonable protection against
cinated cats for at least 4 years, although after 7.5 years, disease. However, it is worth restating that vaccination
titers had declined to low or nondetectable levels.80,81 does not, in general, protect against infection and the de-
Protection against FCV challenge decreased from 85% at velopment of the carrier state of either FCV or FeHV.
3 weeks after vaccination to 63% after 7.5 years. Therefore, vaccinated animals may be subsequently in-
Virus-neutralizing antibody levels to FCV tend to be fected with field viruses and develop persistent infec-
higher than with FeHV, and in general there is reasonable tions without clinical disease. Such vaccinated, field
correlation with protection against disease.82 However, virus carriers are important sources of infection to other
protection has also been seen with lower levels of virus naïve cats and are likely to be partly responsible for the
neutralizing antibody, suggesting cell-mediated and pos- continued high prevalence of FCV and FeHV in the gen-
sible local immunity may also play a role.38,76,83 eral cat population.
 CHAPTER 35 — Feline Viral Upper Respiratory Disease 279

The differences in relative efficacy of FCV and FeHV should be approached with care because any new vac-
vaccines are partly explained by the different level of cine may show either increased or reduced protection
strain variation shown by each of these viruses. For FeHV, against the predominant colony virus. Any decision to
there is only one serotype, and it is likely that vaccines change vaccine may be informed by determining the
protect equally against all field isolates. In contrast, the neutralization profile of vaccine-induced antisera
antigenic differences between FCV isolates mean that no against the predominant colony virus. However, this
single vaccine strain is likely to protect equally against all test is only available at specialist laboratories, is ex-
field viruses. The strains of FCV chosen for use in vac- pensive and time-consuming, and can be difficult to in-
cines, such as F9 and more recently 255, have largely terpret. Rational choice of vaccines also requires infor-
been selected on the basis of being broadly cross-reactive mation on the strains of FCV used in vaccines; however,
in virus neutralization tests in cell culture.31,76,89 Recently, this information is not often included in data sheet in-
companies have sought market advantage through claims formation for marketed vaccines.
of broader cross-reactivity for their vaccine strains. Although live parenteral vaccines are generally con-
Indeed, the ability of a company’s vaccine to neutralize a sidered to be safe, clinical signs have been reported fol-
high proportion of field isolates will probably play an in- lowing their use, particularly in young kittens after
creasingly important role in vaccine marketing. However, their first vaccination (Box 35-1).30,32 Clinical signs may
it is likely that strains of FCV will always exist that show be induced if the vaccine reaches the oral or respiratory
limited neutralization by individual vaccines. It is also mucosa (e.g., if the cat or a littermate licks the injec-
possible that the widespread use of vaccines may select tion site, or if an aerosol is made at the time of injec-
for these “vaccine-resistant” strains.76,89 In the authors’ tion). In addition, in rare cases, vaccine virus may be
opinion it would be desirable, therefore, for the efficacy of able to generalize to the oropharynx even if it is cor-
commercially available vaccines to be regularly monitored rectly administered.21,76
against panels of contemporary field viruses. However, For FCV, molecular typing has confirmed that the ma-
this is not currently routinely performed. jority of vaccine reactions are associated with field virus
Despite designing vaccines to be broadly cross- infection.11,12 However, in some cases, vaccine virus does
reactive, the antigenic diversity of FCV means that in seem to be involved. It is interesting to speculate what
some groups of cats, FCV-related disease may still oc- happens to such vaccine viruses once individual cats start
cur despite regular vaccination. In this situation, it may shedding them. Vaccine safety studies required before live
be appropriate to consider changing vaccines to one vaccines are marketed would suggest they are unlikely to
based on a different strain. However, vaccine changes spread and persist in the population and, until recently,

BOX 35-1
Major Reasons for Vaccine Failures

Vaccine Reactions (Clinical Signs Occurring Vaccine Breakdowns (Clinical Signs Occurring
Within 3 Weeks of Vaccination) 3 Weeks or More Following Vaccination)
Operator Factors Vaccine/Operator Factors
• Vaccine virus gains access to the respiratory mucosa • Incorrect storage, handling or administration
from modified live systemic vaccines through incor- of vaccine.
rect administration (e.g., aerosolization, licking the
Host Factors
injection site).
• Failure to respond to vaccine due to immunosuppres-
Vaccine Factors sion (e.g., infection with feline leukemia or immunode-
• Incomplete attenuation: spread of vaccine virus to ficiency viruses, corticosteroid treatment).
the respiratory mucosa from modified live systemic • Nonspecific factors that may either reduce the response
vaccines through generalization of vaccine virus from to vaccine or increase an individual’s disease susceptibil-
the site of injection. ity (e.g., age, genotype, general health and intercurrent
• Intranasal vaccines may cause mild clinical symp- disease).
toms in some individuals. • Failure to respond to vaccine due to maternally derived
Host and Viral Factors antibody.
• Infection with field virus prior to development of • Respiratory disease due to pathogens not vaccinated
complete vaccine-induced protection. Most fre- against.
quently seen after the first kitten vaccine. • Recrudescent disease in carrier cats (FeHV).
• Respiratory disease due to pathogens not vaccinated Viral Factors
against. • Infection with strains of virus not protected against by
• Recrudescent disease in carrier cats associated with the vaccine (FCV).
stress of vaccination (FeHV). • Overwhelming challenge dose due to overcrowding,
poor hygiene.

Reprinted from Gaskell RM, Radford AD, Dawson S: Feline infectious respiratory disease. In Chandler EA, Gaskell CJ, Gaskell RM,
editors: Feline medicine and therapeutics, ed 3, Oxford, 2003, Blackwell Publishing.
280 PART FIVE — Disorders of the Respiratory Tract: A. Nasal Cavity and Sinuses

vaccine-type viruses have only been identified in recently DISEASE CONTROL IN DIFFERENT SITUATIONS
vaccinated cats. More recently, however, FCV isolates
closely related to those used in live vaccines have been The methods used to control disease caused by FCV and
found in the general cat population, raising the possibility FeHV vary somewhat depending on the husbandry situ-
that, in rare cases, vaccine virus may persist in individual ation in which the cat is housed. In most cases, routine
cat populations, possibly causing disease.9,10,54 vaccination for FCV and FeHV is recommended unless
In contrast to live vaccines, inactivated vaccines have there are strong indications that the risk of infection is
the advantage of not being able to spread or revert to vir- negligible. Disinfection is also an important mainstay of
ulence, and are therefore particularly useful in virus-free control. Because of its lipid envelope, FeHV is highly
colonies. Some inactivated vaccines have also been used susceptible to the effects of all common disinfectants. In
during pregnancy in queens as a useful control measure contrast, FCV shows some degree of resistance to certain
aimed at prolonging the persistence of maternally de- disinfectants. Both viruses, however, are inactivated by a
rived antibody in kittens90; however, individual data number of proprietary products.
sheets should be checked for this indication. Although Household pets are most likely to be exposed to res-
inactivated vaccines are classically considered less effi- piratory pathogens when entering a high-risk situation
cacious than live vaccines, modern adjuvants have led to such as a boarding cattery or a veterinary hospital.
improvements in immunogenicity. Indeed, a long dura- Although transmission may also occur between cats
tion of immunity and reasonable levels of protection in within a neighborhood, the extent to which this occurs
most cats has recently been shown for an adjuvanted, will depend on the level and opportunities for contact
inactivated FCV and FeHV vaccine.80,81 between them. Cats are mainly territorial animals and
Adjuvants may, however, cause clinical problems fol- with neutered animals, once their territory is estab-
lowing vaccination in some individual cats. Both local lished, any contact with other cats is usually brief and
injection site reactions and systemic reactions including does not encourage extensive transmission of pathogens.
pyrexia and lethargy have been observed. Most of these In addition, FCV and FeHV are relatively fragile outside
signs are transient, but local reactions may persist for their hosts, reducing the impact of indirect transmission.
several weeks. In recent years it has become apparent Therefore in order to reduce the risk of respiratory dis-
that in rare cases such reactions may progress to sarco- ease, individual cats should be routinely vaccinated and
mas.91 Although adjuvants, particularly those based on should avoid stress and social contact as far as possible.
aluminum, have been implicated in the etiology of vac- Boarding catteries may be associated with high levels
cine-associated sarcomas, their precise role in the of virus challenge because of the large numbers of cats,
process remains unclear. the high prevalence of FCV and FeHV carriers, and reac-
Live intranasal vaccines induce local mucosal immu- tivation of FeHV shedding induced by stress. Therefore
nity, and this is probably more effective than immunity all cats admitted to a boarding cattery should have an
induced by parenteral vaccines. However, because the up-to-date vaccination record for both FCV and FeHV.
virus replicates at the site of inoculation, clinical signs This means that young kittens should have completed
such as mild sneezing may be seen after several days in the full vaccination course, and adult cats should have
some individuals. Data sheets often state that oral le- had their annual booster, at least 7 days before admis-
sions may also be observed following the use of in- sion. Where the booster vaccination interval has lapsed
tranasal vaccines, and that these tend to heal rapidly. to 18 months, it might be advisable to revaccinate. In sit-
Intranasal vaccines are particularly useful when a rapid uations where rapid protection is required, intranasal
onset of protection is required (e.g., for a cat going into a vaccination may be used if available. However, clients
boarding cattery or in the face of an outbreak of disease). should be aware that such vaccines themselves may in-
In contrast to parenteral vaccines, only a single dose of in- duce mild clinical signs. Although vaccination is helpful
tranasal vaccine is generally required to induce immunity in controlling disease, the owners of catteries should not
following primary vaccination. Complete protection has rely on it solely for disease control. Indeed, even fully
been shown 4 days after intranasal vaccination and par- vaccinated animals may succumb to disease if the viral
tial protection after 2 days. These vaccines may also over- challenge is high enough. Precautions must be taken to
come maternally derived antibody better than parenteral minimize the risk of transmission within the cattery and
vaccines, although in general their use is only licensed in to reduce the concentration of respiratory pathogens in
kittens from 12 weeks of age. Live intranasal vaccines the environment (Box 35-2).
have shown an increase in popularity among some vet- Shelter facilities should apply the same measures as
erinarians, in part because of public concerns about the boarding catteries. However, it is often impossible to
role of inactivated vaccines in vaccine-associated sarco- guarantee levels of vaccination before admission, and
mas. At the time of writing, no intranasal vaccines are it may also be impossible to separate cats to the same
marketed in the United Kingdom. extent. As far as possible, individual cats should be
Boosters for FCV and FeHV vaccines are traditionally segregated or batched and quarantined, and those with
recommended every year. However, concerns about vac- clinical signs isolated. Unless animals can be quaran-
cine site reactions have led to the suggestion that, in tined on arrival for 3 to 4 weeks, systemic vaccines
some circumstances, vaccination frequency may be re- may not have time to become effective. In these cir-
duced based on an informed risk assessment of the like- cumstances it may be advisable to use intranasal vac-
lihood of infection in each individual case.92-94 cines if available.
 CHAPTER 35 — Feline Viral Upper Respiratory Disease 281

BOX 35-2
Recommendations to Prevent Spread of Respiratory Viruses in a Boarding Cattery

• Make sure all incoming cats are fully vaccinated. • Prepare food in a central area.
• Keep cats separate unless they are from the same • If necessary to replace a badly soiled litter tray, follow a
household. similar system to the feed bowls.
• Build catteries with solid partitions between pens. • Between residents, thoroughly disinfect the pen; allow
Ensure frontages are at least 1 meter apart and the sur- to dry; and, preferably, leave empty for 2 days before
face of the pen is made of nonporous material that is reusing.
easily washable. • Put those cats that have signs of respiratory disease, or
• Arrange the pen so the food and water bowls and the are known to have had respiratory disease, or are sus-
litter tray are easily accessible without having to enter pected from previous experience of being carriers, in a
the pen. separate section or at one end of the cattery, and
• Either wash hands in disinfectant between visiting each feed/clean last.
pen, or have a set of disposable gloves on a peg by • Feed cats in the same order every day, and attend to
each pen. Dedicate gloves for use in that pen only; dis- each pen completely before moving to the next.
pose of or thoroughly disinfect them before use with a • Reduce concentration of infectious diseases in the envi-
new boarder. ronment by adequate ventilation, low relative humidity,
• Wear rubber boots, and if it is necessary to enter the and optimal environmental temperature.
pen, step into a disinfectant bath before and after • In mixed boarding catteries and kennels, be aware of
entering. possible transmission of Bordetella bronchiseptica be-
• Either use disposable food trays or have two sets of feed tween cats and dogs. Disinfect between areas, use sep-
bowls used on alternate days. Soak the used set in a arate staff if possible, and avoid visiting coughing dogs
recommended disinfectant for several hours, thor- before cats (or coughing cats before dogs).
oughly rinse, and leave to dry until next use.

Reprinted from Gaskell RM, Radford AD, Dawson S: Feline infectious respiratory disease. In Chandler EA, Gaskell CJ, Gaskell RM,
editors: Feline medicine and therapeutics, ed 3, Oxford, 2003, Blackwell Publishing.

In disease-free breeding catteries, cats should be vac- ternally derived antibody in kittens. (If the latter,
cinated routinely if there is any contact at all with other use an inactivated vaccine, and only if it has a data
cats, and in these situations, inactivated vaccines may be sheet supporting such use.)
preferable. Great care should be taken to avoid bringing • Avoid the use of particular queens with a history of
respiratory pathogens into the colony: any cat with a his- respiratory disease in their kittens.
tory of respiratory disease, or from a household with a • Minimize stressful situations and employ good
history of respiratory disease, may be a carrier. It should management practices.
be remembered that cats may become infected subclini- • Move queens into isolation at least 3 weeks before
cally under cover of maternally derived antibody or vac- term so that the kittens are not exposed to carriers
cine-induced immunity. The greatest risk of infection to in the colony, and so that any FeHV shedding
disease-free households is likely to be from stud cats and episode from the queen induced by the move will
new breeding stock, where exposure is prolonged. Where be over before parturition.
possible, these cats should come from colonies free of • Wean kittens early into isolation as soon as it is fea-
respiratory disease. There is also a slight risk of infection sible (ideally at 4 to 5 weeks) if it is likely the queen
from cat shows, where approximately 25% of cats are is a carrier.
shedding FCV.70 However, direct contact between cats at • Vaccinate all kittens as soon as maternally derived
shows is limited and hygiene measures are usually good. antibody is at a noninterfering level (normally 9⫹
Cats entering the colony should be quarantined for 3 weeks) and keep them in strict isolation until a
weeks to identify animals incubating disease. During week after the second dose (normally at 12 weeks).
quarantine, oropharyngeal swabs should be taken for vi- • Use earlier vaccination schedules: a recent field
ral diagnosis at least twice a week in order to have the study has shown that kittens may respond to par-
best chance of detecting carriers. Even so, there is still enteral vaccination against FCV and FeHV given at
the risk of importing both latent FeHV carriers or low- 3-week intervals from 6 weeks of age.95 Intranasal
level FCV carriers. The necessity to screen for other in- vaccines have also been advocated 7 to 10 days be-
fectious causes of respiratory disease such as B. bron- fore disease normally occurs in a colony, and then
chiseptica and C. felis may also be considered. again at 12 weeks of age. However, it should be
In breeding colonies with endemic disease, attempts kept in mind that such vaccines are not generally li-
to control disease can be made by taking the following censed for this use.
measures: • In some circumstances it may be feasible to restock
• Provide regular vaccination against FCV and FeHV. the colony with virus-free cats and to employ a bar-
• Give booster vaccinations to queens either before rier system to keep the viruses out. A commercial or
mating or during pregnancy to boost levels of ma- institutional colony could achieve this using specific
282 PART FIVE — Disorders of the Respiratory Tract: A. Nasal Cavity and Sinuses

pathogen-free animals. A pedigree cat breeding unit 21. Bennett D, Gaskell RM, Mills A et al: Detection of feline calicivirus
could hand-rear kittens of existing stock in isolation, antigens in the joints of infected cats, Vet Rec 124:329-332, 1989.
22. Dawson S, Bennett D, Carter SD et al: Acute arthritis of cats asso-
bearing in mind that the viruses are very widespread ciated with feline calicivirus infection, Res Vet Sci 56:133-143,
and that it might be difficult to ensure that the 1994.
colony remains virus free, even with vaccination. 23. Dawson S, Smyth NR, Bennett M et al: Effect of primary-stage fe-
line immunodeficiency virus infection on subsequent feline cali-
civirus vaccination and challenge in cats, AIDS 5:747-750, 1991.
REFERENCES 24. Reubel GH, George JW, Barlough JE et al: Interaction of acute fe-
line herpesvirus-1 and chronic feline immunodeficiency virus in-
1. Kadoi K, Kiryu M, Iwabuchi M et al: A strain of calicivirus isolated fections in experimentally infected specific pathogen free cats, Vet
from lions with vesicular lesions on tongue and snout, New Immunol Immunopathol 35:95-119, 1992.
Microbiol 20:141-148, 1997. 25. Reubel GH, George JW, Higgins J et al: Effect of chronic feline im-
2. Hofmann-Lehmann R, Fehr D, Grob M et al: Prevalence of anti- munodeficiency virus infection on experimental feline calicivirus-
bodies to feline parvovirus, calicivirus, herpesvirus, coronavirus, induced disease, Vet Microbiol 39:335-351, 1994.
and immunodeficiency virus and of feline leukemia virus antigen 26. van Vuuren M, Geissler K, Gerber D et al: Characterisation of a po-
and the interrelationship of these viral infections in free-ranging li- tentially abortigenic strain of feline calicivirus isolated from a do-
ons in east Africa, Clin Diagn Lab Immunol 3:554-562, 1996. mestic cat, Vet Rec 144:636-638, 1999.
3. Roerink F, Hashimoto M, Tohya Y et al: Genetic analysis of a ca- 27. Ellis TM: Jaundice in a Siamese cat with in utero feline calicivirus
nine calicivirus: Evidence for a new clade of animal caliciviruses, infection, Aus Vet J 57:383-385, 1981.
Vet Microbiol 69:69-72, 1999. 28. Pedersen NC, Laliberte L, Ekman S: A transient febrile “limping”
4. Hashimoto M, Roerink F, Tohya Y et al: Genetic analysis of the syndrome of kittens caused by two different strains of feline cali-
RNA polymerase gene of caliciviruses from dogs and cats, J Vet civirus, Feline Practice 13(1):26-35, 1983.
Med Sci 61:603-608, 1999. 29. TerWee T, Lauritzen A, Sabara M et al: Comparison of the primary
5. Martella V, Pratelli A, Gentile M et al: Analysis of the capsid pro- signs induced by experimental exposure to either a pneumotrophic
tein gene of a feline-like calicivirus isolated from a dog, Vet or a “limping” strain of feline calicivirus, Vet Microbiol 56:33-45,
Microbiol 85:315-322, 2002. 1997.
6. Geissler K, Schneider K, Platzer G et al: Genetic and antigenic het- 30. Church RE: Lameness in kittens after vaccination, Vet Rec 125:609,
erogeneity among feline calicivirus isolates from distinct disease 1989.
manifestations, Virus Res 48:193-206, 1997. 31. Dawson S, McArdle F, Bennett M et al: Typing of feline calicivirus
7. Glenn M, Radford AD, Turner DC et al: Nucleotide sequence of UK isolates from different clinical groups by virus neutralisation tests,
and Australian isolates of feline calicivirus (FCV) and phylogenetic Vet Rec 133:13-17, 1993.
analysis of FCVs, Vet Microbiol 67:175-193, 1999. 32. Dawson S, McArdle F, Bennett D et al: Investigation of vaccine re-
8. Rice CC, Kruger JM, Venta PJ et al: Genetic characterization of 2 actions and breakdowns after feline calicivirus vaccination, Vet Rec
novel feline caliciviruses isolated from cats with idiopathic lower 132:346-350, 1993.
urinary tract disease, J Vet Intern Med 16:293-302, 2002. 33. Knowles JO, Gaskell RM, Gaskell CJ et al: Prevalence of feline cali-
9. Pedersen NC, Elliott JB, Glasgow A et al: An isolated epizootic of civirus, feline leukaemia virus and antibodies to FIV in cats with
hemorrhagic-like fever in cats caused by a novel and highly viru- chronic stomatitis, Vet Rec 124:336-338, 1989.
lent strain of feline calicivirus, Vet Microbiol 73:281-300, 2000. 34. Thompson RR, Wilcox GE, Clark WT et al: Association of cali-
10. Horimoto T, Takeda Y, Iwatsuki-Horimoto K et al: Capsid protein civirus infection with chronic gingivitis and pharyngitis in cats,
gene variation among feline calicivirus isolates, Virus Genes JSAP 25:207-210, 1984.
23:171-174, 2001. 35. Tenorio AP, Franti CE, Madewell BR et al: Chronic oral infections
11. Radford AD, Bennett M, McArdle F et al: The use of sequence of cats and their relationship to persistent oral carriage of feline
analysis of a feline calicivirus (FCV) hypervariable region in the calici-, immunodeficiency, or leukemia viruses, Vet Immunol
epidemiological investigation of FCV related disease and vaccine Immunopath 29:1-14, 1991.
failures, Vaccine 15:1451-1458, 1997. 36. Waters L, Hopper CD, Gruffydd-Jones TJ et al: Chronic gingivitis
12. Radford AD, Dawson S, Wharmby C et al: Comparison of serolog- in a colony of cats infected with feline immunodeficiency virus and
ical and sequence-based methods for typing feline calicivirus iso- feline calicivirus, Vet Rec 132:340-342, 1993.
lates from vaccine failures, Vet Rec 146:117-123, 2000. 37. Reubel GH, Hoffmann DE, Pedersen NC: Acute and chronic fauci-
13. Sykes JE, Studdert VP, Browning GF: Detection and strain differ- tis of domestic cats: A feline calicivirus induced disease, Vet Clin
entiation of feline calicivirus in conjunctival swabs by RT-PCR of North Am Small Anim Pract 22:1347-1360, 1992.
the hypervariable region of the capsid protein gene, Arch Virol 38. Knowles JO, McArdle F, Dawson S et al: Studies on the role of fe-
143:1321-1334, 1998. line calicivirus in chronic stomatitis in cats, Vet Microbiol 27:205-
14. Gaskell R, Willoughby K: Herpesviruses of carnivores, Vet 219, 1991.
Microbiol 69:73-88, 1999. 39. Poulet H, Brunet S, Soulier M et al: Comparison between acute
15. Harder TC, Harder M, Vos H et al: Characterization of phocid oral/respiratory and chronic stomatitis/gingivitis isolates of feline
herpesvirus-1 and -2 as putative alpha- and gammaherpesviruses calicivirus: Pathogenicity, antigenic profile and cross-neutralisation
of North American and European pinnipeds, J Gen Virol 77:27-35, studies, Arch Virol 145:243-261, 2000.
1996. 40. Maggs DJ, Lappin MR, Nasisse MP: Detection of feline herpesvirus-
16. Lebich M, Harder TC, Frey HR et al: Comparative immunological specific antibodies and DNA in aqueous humor from cats with or
characterization of type-specific and conserved B-cell epitopes of without uveitis, Am J Vet Res 60:932-936, 1999.
pinniped, felid and canid herpesviruses, Arch Virol 136:335-347, 41. Nasisse MP, Glover TL, Moore CP et al: Detection of feline her-
1994. pesvirus 1 DNA in corneas of cats with eosinophilic keratitis or
17. Willoughby K, Bennett M, McCracken CM et al: Molecular phylo- corneal sequestration, Am J Vet Res 59:856-858, 1998.
genetic analysis of felid herpesvirus 1, Vet Microbiol 69:93-97, 42. Nasisse MP, Davis BJ, Guy JS et al: Isolation of feline herpesvirus
1999. 1 from the trigeminal ganglia of acutely and chronically infected
18. Grail A, Harbour DA, Chia W: Restriction endonuclease mapping cats, J Vet Intern Med 6:102-103, 1992.
of the genome of feline herpesvirus type 1, Arch Virol 116:209-220, 43. Stiles J: Feline herpesvirus, Vet Clin North Am Small Anim Pract
1991. 30:1001-1014, 2000.
19. Horimoto T, Limcumpao JA, Xuan X et al: Heterogeneity of feline 44. Flecknell PA, Orr CM, Wright AI et al: Skin ulceration associated
herpesvirus type 1 strains, Arch Virol 126:283-292, 1992. with herpesvirus infection in cats, Vet Rec 104:313-315, 1979.
20. Maeda K, Kawaguchi Y, Ono M et al: Comparisons among feline 45. Junge RE, Miller RE, Boever WJ et al: Persistent cutaneous ulcers
herpesvirus type 1 isolates by immunoblot analysis, J Vet Med Sci associated with feline herpesvirus type 1 infection in a cheetah, J
57:147-150, 1995. Am Vet Med Assoc 198:1057-1058, 1991.
 CHAPTER 35 — Feline Viral Upper Respiratory Disease 283

46. Hargis AM, Ginn PE: Feline herpesvirus 1-associated facial and 70. Coutts AJ, Dawson S, Willoughby K et al: Isolation of feline respi-
nasal dermatitis and stomatitis in domestic cats, Vet Clin North Am ratory viruses from clinically healthy cats at UK cat shows, Vet Rec
Small Anim Pract 29:1281-1290, 1999. 135:555-556, 1994.
47. Hickman MA, Reubel GH, Hoffman DE et al: An epizootic of feline 71. Radford AD: Unpublished observations, 2003.
herpesvirus, type 1 in a large specific pathogen-free cat colony and 72. Gaskell RM, Povey RC: Experimental induction of feline viral
attempts to eradicate the infection by identification and culling of rhinotracheitis (FVR) virus re-excretion in FVR-recovered cats, Vet
carriers, Lab Anim 28:320-329, 1994. Rec 100:128-133, 1977.
48. Stiles J, McDermott M, Bigsby D et al: Use of nested polymerase 73. Gaskell RM, Dennis PE, Goddard LE et al: Isolation of felid her-
chain reaction to identify feline herpesvirus in ocular tissue from pesvirus 1 from the trigeminal ganglia of latently infected cells, J
clinically normal cats and cats with corneal sequestra or conjunc- Gen Virol 66:391-394, 1985.
tivitis, Am J Vet Res 58:338-342, 1997. 74. Reubel GH, Ramos RA, Hickman MA et al: Detection of active and
49. Stiles J, McDermott M, Willis M et al: Comparison of nested poly- latent feline herpesvirus 1 infections using the polymerase chain
merase chain reaction, virus isolation, and fluorescent antibody reaction, Arch Virol 132:409-420, 1993.
testing for identifying feline herpesvirus in cats with conjunctivi- 75. Gaskell CJ, Gaskell RM, Dennis PE et al: Efficacy of an inactivated
tis, Am J Vet Res 58:804-807, 1997. feline calicivirus (FCV) vaccine against challenge with United
50. Sykes JE, Anderson GA, Studdert VP et al: Prevalence of feline Kingdom field strains and its interaction with the FCV carrier state,
Chlamydia psittaci and feline herpesvirus 1 in cats with upper res- Res Vet Sci 32:23-26, 1982.
piratory tract disease, J Vet Intern Med 13:153-162, 1999. 76. Pedersen NC, Hawkins KF: Mechanisms of persistence of acute
51. Weigler BJ, Babineau CA, Sherry B et al: High sensitivity poly- and chronic feline calicivirus infections in the face of vaccination,
merase chain reaction assay for active and latent feline herpesvirus- Vet Microbiol 47:141-156, 1995.
1 infections in domestic cats, Vet Rec 140:335-338, 1997. 77. Povey RC, Koonse H, Hays MB: Immunogenicity and safety of an
52. Vogtlin A, Fraefel C, Albini S et al: Quantification of feline her- inactivated vaccine for the prevention of rhinotracheitis, caliciviral
pesvirus 1 DNA in ocular fluid samples of clinically diseased cats disease, and panleukopenia in cats, J Am Vet Med Assoc 177:347-
by real-time TaqMan PCR, J Clin Microbiol 40:519-523, 2002. 350, 1980.
53. Burgesser KM, Hotaling S, Schiebel A et al: Comparison of PCR, 78. Scott FW: Evaluation of a feline viral rhinotracheitis-feline cali-
virus isolation, and indirect fluorescent antibody staining in the civirus disease vaccine, Am J Vet Res 38:229-34, 1997.
detection of naturally occurring feline herpesvirus infections, J Vet 79. Bittle JL, Rubic WJ: A feline calicivirus vaccine combined with fe-
Diagn Invest 11:122-126, 1999. line viral rhinotracheitis and feline panleukopenia vaccine, Feline
54. Radford AD, Sommerville L, Ryvar R et al: Endemic infection of a Pract 5(6):13-15, 1975.
cat colony with a feline calicivirus closely related to an isolate used 80. Scott FW, Geissinger CM: Duration of immunity in cats vaccinated
in live attenuated vaccines, Vaccine 19:4358-4362, 2001. with an inactivated feline panleukopenia, herpesvirus and cali-
55. Radford AD, Sommerville LM, Dawson S et al: Molecular analysis civirus vaccine, Feline Pract 25(4):12-19, 1997.
of isolates of feline calicivirus from a population of cats in a res- 81. Scott FW, Geissinger CM: Long-term immunity in cats vaccinated
cue shelter, Vet Rec 149:477-481, 2001. with an inactivated trivalent vaccine, Am J Vet Res 60:652-658, 1999.
56. Helps C, Lait P, Tasker S et al: Melting curve analysis of feline cali- 82. Povey C, Ingersoll J: Cross-protection among feline calicviruses,
civirus isolates detected by real-time reverse transcription PCR, J Infect Immun 11:877-885, 1975.
Virol Meth 106:241-244, 2002. 83. Tham KM, Studdert MJ: Antibody and cell-mediated immune re-
57. Nasisse MP, Dorman DC, Jamison KC et al: Effects of valacyclovir sponses to feline calicivirus following inactivated vaccine and
in cats infected with feline herpesvirus 1, Am J Vet Res 58:1141- challenge, J Vet Med 34:640-654, 1987.
1144, 1997. 84. Orr CM, Gaskell CJ, Gaskell RM: Interaction of a combined feline
58. Nasisse MP, Guy JS, Davidson MG et al: In vitro susceptibility of viral rhinotracheitis-feline calicivirus vaccine and the FVR carrier
feline herpesvirus-1 to vidarabine, idoxuridine, trifluridine, acy- state, Vet Rec 103:200-202, 1978.
clovir, or bromovinyldeoxyuridine, Am J Vet Res 50:158-160, 1989. 85. Povey RC, Wilson MR: A comparison of inactivated feline viral
59. Tennant B, Willoughby K: The use of enteral nutrition in small ani- rhinotracheitis and feline caliciviral disease vaccines with live-
mal medicine, Compendium of Continuing Education 15:1054, 1993. modified viral vaccines, Feline Pract 8(3):35-42, 1978.
60. Binns SH, Dawson S, Speakman AJ et al: A study of feline upper 86. Bittle JL, Rubic WJ: Studies of feline viral rhinotracheitis vaccine,
respiratory tract disease with reference to prevalence and risk fac- Vet Med Small Anim Clin 69:1503-1505, 1974.
tors for infection with feline calicivirus and feline herpesvirus, J Fel 87. Johnson RP, Povey RC: Transfer and decline of maternal antibody
Med Surg 2:123-133, 2000. to feline calicivirus, Can Vet J 24:6-9, 1983.
61. Harbour DA, Howard PE, Gaskell RM: Isolation of feline calicivirus 88. Gaskell RM, Povey RC: Transmission of feline viral rhinotracheitis,
and feline herpesvirus from domestic cats 1980 to 1989, Vet Rec Vet Rec 111:359-362, 1982.
128:77-80, 1991. 89. Lauritzen A, Jarrett O, Sabara M: Serological analysis of feline cali-
62. Mochizuki M, Kawakami K, Hashimoto M et al: Recent epidemio- civirus isolates from the United States and United Kingdom, Vet
logical status of feline upper respiratory infections in Japan, J Vet Microbiol 56:55-63, 1997.
Med Sci 62:801-803, 2000. 90. Iglauer F, Gartner K, Morstedt R: Maternal protection against feline
63. Wardley RC, Povey RC: Aerosol transmission of feline calicivirus: respiratory disease by means of booster vaccinations during preg-
An assessment of its epidemiological importance, Brit Vet J nancy: A retrospective clinical study, Kleintierpraxis 34:235, 1989.
133:404-508, 1977. 91. Morrison WB, Starr RM: Vaccine-associated feline sarcomas, J Am
64. Wardley RC, Povey RC. The clinical disease and patterns of excre- Vet Med Assoc 218:697-702, 2001.
tion associated with three different strains of feline calicivirus, Res 92. Elston T, Rodan H, Flemming D et al: 1998 report of the American
Vet Sci 23:7-14, 1977. Association of Feline Practitioners and Academy of Feline Medicine
65. Wardley RC. Feline calicivirus carrier state: A study of the Advisory Panel on Feline Vaccines, J Am Vet Med Assoc 212:227-
host/virus relationship, Arch Virol 52:243-249, 1976. 241, 1998.
66. Johnson RP: Antigenic change in feline calicivirus during persis- 93. Gaskell RM, Gettinby G, Graham SJ et al: Veterinary Products
tent infection, Can J Vet Res 56:326-330, 1992. Committee working group report on feline and canine vaccination,
67. Radford AD, Turner PC, Bennett M et al: Quasispecies evolution of Vet Rec 150:126-134, 2002.
a hypervariable region of the feline calicivirus capsid gene in cell 94. Gaskell RM, Gettinby G, Graham SJ et al: Veterinary Products
culture and in persistently infected cats, J Gen Virol 79:1-10, 1998. Committee (VPC) working group on feline and canine vaccination:
68. Kreutz LC, Johnson RP, Seal BS: Phenotypic and genotypic varia- Final report to the VPC (PB 6432), London, 2002, Departmental for
tion of feline calicivirus during persistent infection of cats, Vet Environmental, Food and Rural Affairs.
Microbiol 59:229-236, 1998. 95. Dawson S, Willoughby K, Gaskell RM et al: A field trial to assess
69. Wardley RC, Gaskell RM, Povey RC: Feline respiratory viruses— the effect of vaccination against feline herpesvirus, feline cali-
their prevalence in clinically healthy cats, J Sm Anim Pract 15:579- civirus and feline panleucopenia virus in 6-week-old kittens, J
586, 1974. Feline Med Surg 3:17-22, 2001.