Infectious Diseases of The Dog and Cat, 3rd Edition: CHAPTER 16 Feline Respiratory Disease

Infectious Diseases of the Dog and Cat, 3rd Edition
CHAPTER 16 Feline Respiratory Disease

Rosalind M. Gaskell
Susan Dawson
Alan Radford
ETIOLOGY
Feline infectious respiratory disease is most commonly seen in cats that are grouped together, as in multicat
households, boarding catteries, and breeding establishments. The disease is multifactorial, with several etiologic
agents involved and a significant number of other risk factors identified.
3,4,94
The majority of cases of infectious respiratory disease are caused by one of two viruses: feline herpesvirus-1
(FHV-1, or feline rhinotracheitis virus) and feline calicivirus (FCV). FHV-1 generally induces more severe disease
than FCV does, but FCV appears to be relatively more common.
7,27,60
This prevalence may relate to the antigenic
diversity of the virus and the inability of current vaccines to protect equally well against all FCV strains.
47,60
Increasingly apparent is that Bordetella bronchiseptica is also a primary pathogen of the feline respiratory tract,
although its precise contribution to disease in the field is not yet fully established.
3,24,89
Interestingly, transmission
of the organism between dogs and cats may occur, which has implications for disease control in both
species.
3,5,15,24
Chlamydophila felis (previously Chlamydia psittaci var. felis) is also involved in feline respiratory disease,
although it is considered predominantly a conjunctival pathogen (see also Chapter 30). Other agents that have been
implicated in the syndrome include mycoplasmas and other bacteria, feline reovirus, and cowpox virus.
27
Feline Herpesvirus-1
FHV-1 is a typical -herpesvirus containing double-stranded DNA, with a glycoprotein-lipid envelope. As in
most herpesviruses, FHV-1 is relatively fragile in the external environment and is highly susceptible to the
effects of common disinfectants. It can survive for only up to 18 hours in a damp environment, less in dry
conditions. It is also relatively unstable as an aerosol.
As well as infecting domestic cats, FHV-1 has been shown to infect several other members of the
Felidae.
13,70,104
The virus is also very closely related genetically and antigenically to canine herpesvirus-1 and
phocine (seal) herpesvirus-1 (PhV-1), and cross-protection between feline and PhV-1 has been reported.
55,110
FHV-1 has little strain variation. Most isolates produce a relatively uniform disease, although some show
reduced or increased virulence. Antigenically, all strains belong to one serotype, and apart from some minor
differences, they are relatively homogeneous on restriction enzyme analysis of their DNA. Therefore no easy
method is currently available to study the role of individual FHV-1 isolates in disease.
145
16
16.1
16.1.1
CHAPTER 16 Feline Respiratory Disease Page 1 of 21
Feline Calicivirus
FCV is a small, unenveloped, single-stranded RNA virus, a member of the Vesivirus genus of the calicivirus
family. Both domestic cats and other members of the Felidae family can be infected, and a similar virus has
also been isolated from lions.
13,45
Although dogs have their own genetically distinct calicivirus,
56,82

caliciviruses antigenically and genetically related to FCV have also been detected in dogs (see Chapter
8),
35,54,83
and some epidemiologic evidence suggests a link between the two.
4
FCV is slightly more resistant than is FHV-1, surviving for up to a week in the external environment or possibly
longer if conditions are damp. The virus is not as susceptible to the effects of disinfectants as FHV-1,
20
but a
useful disinfectant for both viruses is bleach diluted 1 part in 32 in water with added detergent.
A large number of different strains of FCV exists, which vary slightly in antigenicity and pathogenicity,
although they are all sufficiently cross-reactive to be classified as one serotype. Genetically, these strains appear
to represent one large group or genogroup, although again, considerable variability may be seen between
isolates, particularly in immunogenic regions of the viral capsid gene.
*
This genetic diversity is useful
epidemiologically in that it allows differentiation between FCV strains.
71,73-75,96
Most strains of FCV are closely related enough to induce some degree of cross-protection, but cats can still be
sequentially infected with different viruses and show varying degrees of clinical illness. Some isolates appear to
be more immunogenic and cross-reactive than do others, and several such strains (e.g., the original vaccine
strain F9 and strain 255) have been widely used in vaccines. However, no single strain is likely to protect
equally well against all field isolates, and some evidence indicates that the percentage of isolates neutralized by
such strains may be decreasing, possibly caused by immune selection pressures from widespread vaccine
use.
8,27,47,60
Routine monitoring of vaccine efficacy against current isolates would be useful.
* References 1, 30, 31, 40, 46, 72
B. bronchiseptica
B. bronchiseptica is an aerobic, gram-negative coccobacillus that is a well-known respiratory pathogen in dogs,
swine, and rodents. It also causes occasional opportunistic infection in people: indeed, a case has been reported
in a veterinary student.
24
(See Public Health Considerations, Chapter 6, for further information on this risk.) In
the past, B. bronchiseptica was thought to play only a secondary role in feline respiratory disease, but it is now
established as a primary pathogen in cats. Respiratory disease has been reproduced in Bordetella-free,
specific-pathogenfree (SPF) cats after aerosol or nasal challenge,
12,42,44,109
and a large number of field cases
have been reported.
However, a significant number of factors likely play a role in whether disease occurs in
the field, and various risk factors for B. bronchiseptica infection in cats have been identified in epidemiologic
studies.
3
References 41, 48, 89, 101, 108
Other Organisms
C. felis causes acute to chronic conjunctivitis in cats, although respiratory signs may also be seen. The
prevalence of C. felis in cats with conjunctival or upper respiratory tract disease has been reported in studies
145
146
16.1.2
16.1.3
16.1.4
using polymerase chain reaction (PCR) to range between 14.3%
94
and 59%.
7
The disease is discussed in more
detail in Chapter 30.
Reoviruses have been occasionally isolated from cats, and conjunctival and respiratory signs have been induced
after experimental inoculation. However, no evidence has been found that reoviruses are important as
respiratory pathogens in cats in the field.
Cowpox virus infection in cats causes primarily skin lesions, but occasionally respiratory or ocular signs may
also be seen (see Chapter 19). The reservoir hosts of cowpox virus in Europe are small wild mammals, and cats
occasionally become infected by contact through hunting. Other orthopoxviruses, that may infect cats, exist in
other parts of the world.
The role of mycoplasmas in feline respiratory disease is not clear. Undoubtedly, they can be important as
secondary pathogens, but their role as primary agents is more equivocal (see Chapter 32). Infection is common
in both colony cats and household pets, and mycoplasmas have been isolated from both diseased and healthy
animals. Increasing evidence indicates that mycoplasmas may be associated with disease in the lower
respiratory tract; however, their role in upper respiratory tract disease is less clear.
10,32,76
Mycoplasmas have
been isolated in pure culture from cases of bronchopneumonia, which have responded to antimycoplasmal
therapy.
25
Other bacteria such as Staphylococcus spp., Streptococcus spp., Pasteurella multocida, and
Escherichia coli are thought to play a role as secondary invaders in feline respiratory disease.
EPIDEMIOLOGY
Feline Herpesvirus-1 and Feline Calicivirus Infections
FHV-1 and FCV are fairly widespread in the general cat population, with a higher prevalence in multicat
households. The viruses are mainly shed in ocular, nasal, and oral secretions, and spread is largely by direct
contact with an infected cat. Acutely infected animals are clearly one of the most important sources of virus, but
infection also commonly occurs from clinically recovered carrier cats. In some situations, particularly within a
cattery, indirect transmission may also occur. Contaminated secretions may be present on cages, feeding and
cleaning utensils, and on personnel. However, because the viruses are relatively short lived outside the cat, the
environment is usually not a long-term source of infection.
Aerosols are not thought to be of major importance for the spread of FHV-1 and FCV. Cats do not appear to
produce an infectious aerosol for these agents during normal respiration, although sneezed macrodroplets may
transmit infection over a distance of 1 to 2 meters.
Despite vaccination, carriers are widespread in the population and are probably the main reason why these
viruses are so successful. An understanding of the FHV-1 and FCV carrier states is important to help determine
strategies for control.
Carrier State for Feline Herpesvirus-1
As with other -herpesviruses, virtually all recovered cats become latently infected carriers. However,
intermittent episodes of detectable virus shedding (reactivation) may occur, particularly after periods of stress
(Fig. 16-1). During such episodes, infectious virus is present in oronasal and conjunctival secretions, and cats
16.2
16.2.1
16.2.2
may infect other cats. The epidemiologic significance of PCR-positive cats, which are negative by traditional
virus culture, is not clear, but they are likely to be less infectious.
6,95,107
Virus reactivation may occur spontaneously but is most likely after stress, for example, going into a boarding
cattery, to a cat show, or to stud. Glucocorticoid treatment can also induce shedding, but using this drug to
detect carriers is inadvisable because severe disease may occasionally result. Some carrier cats appear to shed
virus more frequently than do others and therefore are of greater epidemiologic importance.
Shedding does not occur immediately after the stress; a lag period of approximately 1 week occurs, followed by
a shedding episode of from 1 to 2 weeks. Thus carrier cats are most likely to be infectious for up to 3 weeks
after a stress factor. In some cases, carriers show recrudescence of mild clinical signs while they are shedding,
which can be a useful indicator that they are likely to be infectious.
The stress of parturition and lactation may also precipitate virus shedding in latently infected queens, but
whether or not the kittens develop disease depends on their levels of maternally derived antibody (MDA). On
some occasions, kittens with low levels of MDA may become subclinically infected and become latent carriers
without showing clinical signs. Such a mechanism is obviously ideal for the virus because it can spread to the
next generation without harming its host.
As with some other herpesviruses, FHV-1 remains latent in carriers in the trigeminal ganglia, although virus has
also been detected by PCR in a large number of other tissues.
81,107
The latent carrier state is almost certainly
lifelong, but a refractory phase of several months occurs after a period of virus shedding when animals are less
likely to experience another reactivation episode.
Carrier State for Feline Calicivirus
Unlike FHV-1 carriers, FCV carriers shed virus more or less continuously and are mostly therefore always
infectious to other cats (Fig. 16-2). The virus persists in tonsillar and other oropharyngeal tissues. In some cats,
the carrier state appears to be lifelong, but most animals at some point spontaneously recover and appear to
eliminate virus. In some experimental studies, most cats were shedding FCV 30 days after infection, and by 75
days, approximately 50% of cats were still shedding. This proportion continues to decline, with only a minority
of animals becoming long-term carriers. In other studies, carrier states have been difficult to reproduce,
suggesting that virus strain differences or other factors may be involved. Some evidence indicates that
preexisting feline immunodeficiency virus (FIV) infection may potentiate FCV shedding from carriers, either in
terms of duration or titer of virus.
16,79
FCV carriers have been arbitrarily divided into high, medium, and low level, each shedding a fairly constant
amount of virus that fluctuates around a mean for that individual cat. High-level shedders are very infectious
and easily detected by oropharyngeal swabbing; low-level shedders are less infectious, and a series of swabs
taken over several weeks may be necessary to identify them.
FCV carriers are very common, and prevalence rates are still similar to those reported some years ago, before
the introduction of vaccination. Surveys have shown that approximately 20% to 30% of cats, depending on the
population studied, are shedding FCV.
4,27,74
Although many of these cats will be carriers, some may be
undergoing reinfection, and others may be undergoing primary infection with an nonpathogenic strain.
Vaccination protects against disease but not infection or the carrier state, and mathematical modeling studies
suggest that a reduction in FCV prevalence is unlikely with the current levels of vaccine efficacy.
77
146
16.2.3
Fig 16-1 FHV-1 carrier state: epidemiology. (From Gaskell RM, Radford AD,
Dawson S. 2004. Feline infectious respiratory disease, p 583. In
Chandler EA, Gaskell CJ, Gaskell RM [eds], Feline medicine and
therapeutics, ed 3, Blackwell Publishing, Oxford. Used with permission.)
B. bronchiseptica Infection
Serosurveys have shown that B. bronchiseptica is widespread in the cat population. Seroprevalence of between
24% and 79% and isolation rates of up to 47% have been reported, depending on the type and clinical status of
the population tested.
*
In a large-scale epidemiologic survey of cats in the United Kingdom with and without
respiratory disease, 11% of 740 cats were found to be shedding B. bronchiseptica from the oropharynx, with a
higher positive number in rescue catteries and in households with larger numbers of cats.
3
An association
between B. bronchiseptica infection and respiratory disease was found in the rescue cattery population, which
fits with previous empirical observations that the organism is more likely to cause disease in stressful, crowded
situations.
146
147
16.2.4
Also apparent is that transmission of this bacterium may occur between dogs and cats, which clearly has
implications for control, especially where dogs and cats are housed on the same premises. Epidemiologic
studies have shown that contact with dogs with recent respiratory disease was found to be a risk factor for B.
bronchiseptica infection in cats.
3
In addition, typing of isolates from dogs and cats using pulsed-field gel
electrophoresis (PFGE) has shown that isolates from both species on the same premises are likely to be
similar.
5,24
Another report showed two cats developing respiratory disease following contact with two dogs
with kennel cough, and B. bronchiseptica isolated from all four animals were found to be the same using
PFGE.
15
Interestingly, Foley and colleagues
24
noted that the majority of isolates circulating in dogs and cats in
two shelters in the United States appeared to be similar to a canine and feline vaccine strain.
Epidemiologic evidence suggests that a carrier state may exist in cats with Bordetella infection, with 9% of
clinically healthy cats shedding the organism.
3
Experimental work has shown that B. bronchiseptica is shed in
both oropharyngeal and nasal secretions, in some cases for at least 19 weeks after infection.
12
In the same
study, B. bronchiseptica was detected in two seropositive queens after parturition despite being negative
beforehand, suggesting the stress of parturition may have initiated shedding.
* References 2, 3, 24, 42, 89.
PATHOGENESIS
Feline Herpesvirus-1 Infection
The natural routes of infection for FHV-1 are nasal, oral, and conjunctival, and virus replication takes place
predominantly in the mucosae of the nasal septum, turbinates, nasopharynx, and tonsils. Virus shedding can be
detected in oropharyngeal and nasal swabs as early as 24 hours after infection and generally persists for 1 to 3
weeks.
147
16.3
16.3.1
Fig 16-2 FCV carrier state: epidemiology. (Flow diagram from Gaskell RM,
Radford AD, Dawson S. 2004. Feline infectious respiratory disease, p
584. In Chandler EA, Gaskell CJ, Gaskell RM [eds], Feline medicine and
therapeutics, ed 3, Blackwell Publishing, Oxford. Used with permission.
Virus drawing courtesy of University of Georgia, Athens, Ga.)
Viremia is rare because virus replication is normally restricted to areas of lower body temperature, such as the
respiratory tract. However, viremia has occasionally been reported, and generalized disease may be seen,
particularly in debilitated animals or in neonatal kittens.
Infection leads to areas of multifocal epithelial necrosis, with neutrophilic infiltration and exudation with fibrin.
In early infections, intranuclear inclusion bodies may be seen. Viral damage can also lead to osteolytic changes
in the turbinate bones. Lesions normally take between 2 and 3 weeks to resolve, although bone damage to the
turbinates may be permanent. Primary lung involvement may occur but is rare. Secondary bacterial infection
can enhance the pathogenic effect of FHV-1; thus bacterial sinusitis or pneumonia is possible.
147
148
Feline Calicivirus Infection
Similar to FHV-1, the natural routes of infection for FCV are nasal, oral, and conjunctival. Virus replication
mainly occurs in the oral and respiratory tissues, although some differences between strains can be found. Some
strains have a predilection for the lung, and others have been found in the macrophages within the synovial
membrane of joints.
14,100
Virus may also be found in visceral tissues and feces and occasionally in the urine.
Oral ulcers are the most prominent pathologic feature of FCV infection. These ulcers begin as vesicles, which
subsequently rupture, with necrosis of the overlying epithelium and infiltration of neutrophils at the periphery
and the base. Healing takes place over 2 to 3 weeks.
Pulmonary lesions appear to result from an initial focal alveolitis, which leads to areas of acute exudative
pneumonia and then to the development of a proliferative, interstitial pneumonia. Although primary interstitial
pneumonia can occur in FCV infection, particularly with more virulent strains, it has probably been
overemphasized in the past as a result of experimental studies using aerosol challenge rather than the more
natural oronasal routes.
Lesions seen in FCV-infected joints consist of an acute synovitis with thickening of the synovial membrane and
an increased amount of synovial fluid within the joint.
In most species, the primary route of infection with B. bronchiseptica appears to be via the oronasal cavity
where the organism colonizes mucosal surfaces. The bacterium uses several virulence factors to adhere to the
cilia of the respiratory epithelium. Once attached, ciliostasis and destruction of the cilia occur, resulting in the
failure of the mucociliary clearance mechanism and facilitating further colonization and persistence of bacteria.
The release of toxins from B. bronchiseptica following colonization is responsible for local and systemic
inflammatory damage.
In dogs, the organism appears to target mainly the mucosa of the trachea and bronchi, leading to
tracheobronchitis. Although the precise pathogenesis of the disease in cats is unclear, upper respiratory tract
involvement appears to be more common. However, clearly in some instances, the lower respiratory tract may
also be targeted, given that bronchopneumonia and coughing may occur.
Although B. bronchiseptica may appear to be a primary pathogen in cats, undoubtedly other factors such as
combined infections with the respiratory viruses and stress factors such as weaning, overcrowding, and poor
hygiene and ventilation all play roles. Such factors may account for the severe cases of bronchopneumonia that
have been reported in the field.
CLINICAL FINDINGS
Whatever the respiratory pathogen, the observed clinical signs will depend on a large number of factors, such as
the infecting dose and strain of the agent, the general health and husbandry conditions of the cat, the nature of its
microbial flora, and any preexisting immunity (Table 16-1). Concurrent infection with immunosuppressive viruses
such as FIV and feline leukemia virus may lead to more severe disease.
16,78,79
148
149
16.3.2
16.3.3
16.4
Feline Herpesvirus-1 Infection
In susceptible animals, FHV-1 infection generally causes a severe upper respiratory disease. The incubation
period is usually 2 to 6 days but may be longer with lower levels of challenge virus.
Early signs include depression, marked sneezing, inappetence, and pyrexia, followed rapidly by serous ocular
and nasal discharges (Fig. 16-3). These initial clinical signs may be accompanied by excessive salivation with
drooling. Conjunctivitis, sometimes with severe hyperemia and chemosis, typically develops, and copious
oculonasal discharges occur. These discharges gradually become mucopurulent, and crusting of the external
nares and eyelids can occur (Fig. 16-4). In severe cases, dyspnea and coughing may also develop. Oral
ulceration can occur with FHV-1 infection, but it is rare. Occasionally, generalized infections and primary viral
pneumonia may occur, particularly in young or debilitated animals.
Table 16-1 Essential Features of Clinical Respiratory Disease Related to the
Pathogen Involved
FEATURE FHV-1
FCV
a
Bb ChF
Lethargy +++ + + +
Sneezing +++ + ++ +
Conjunctivitis ++ +
+++
b
Hypersalivation ++

c

Ocular discharge +++ + (+) +++
Nasal discharge +++ + ++ +
Oral ulceration (+) +++
Keratitis +
Coughing (+) ++
Pneumonia (+) (+) + +/
Lameness +
Adapted from Gaskell RM, Radford AD, Dawson S. 2004. Feline infectious respiratory disease, p 580. In Chandler EA,
Gaskell CJ, Gaskell RM (eds), Feline medicine and therapeutics, ed 3, Blackwell Publishing, Oxford. Used with permission.
FHV-1, Feline herpesvirus; FCV, feline calicivirus; Bb, Bordetella bronchiseptica; ChF, Chlamydophila felis; +++, marked; ++,
moderate;
+, mild; (+), less common; +/, subclinical; , absent.
a Strain variation.
b Often persistent.
c Slight wetness may be seen around the mouth if ulcers present.
Other manifestations of FHV-1 infection include ulcerative and interstitial keratitis and corneal sequestration; a
possible association with uveitis has also been reported (Fig. 16-5).
51
Improved diagnosis, for example, using
PCR, has lead to greater recognition of such conditions.
64,91
Skin ulcers and dermatitis syndrome in domestic
cats and cheetahs,
33,34,62a
and nervous signs have been described, but these are likely to be rare sequels to
infection.
Although abortion is a feature of some other -herpesvirus infections, experimental studies have suggested that,
in FHV-1, the severe systemic effects of the illness, rather than a direct effect of the virus itself, are most likely
16.4.1
the cause of abortion. Indeed, in an investigation of a natural outbreak of FHV-1 in SPF cats, no cases of
abortion were seen, even in severely affected pregnant queens.
37
In very young kittens or immunosuppressed cats, the mortality rate may be high, but on the whole, mortality
with FHV-1 is low. Clinical signs generally resolve within 10 to 20 days. However, in some cats the acute
damage may have been severe enough to lead to permanent damage to the mucosae and turbinates, leaving
individual cats prone to chronic bacterial rhinitis, turbinate osteomyelitis, sinusitis, and conjunctivitis.
Short-nosed purebred cats such as Persians or Himalayans appear to have an increased tendency to develop
chronic upper respiratory complications, although the reasons for this are not yet clear.
Fig 16-3 A litter of kittens with early FHV-1 infection. (From Gaskell RM,
Radford AD, Dawson S. 2004. Feline infectious respiratory disease, p
588. In Chandler EA, Gaskell CJ, Gaskell RM [eds], Feline medicine and
therapeutics, ed 3, Blackwell Publishing, Oxford. Used with permission.)
Fig 16-4 Kitten with FHV-1 infection showing mucopurulent discharges typical
of the later stages of the disease. (Courtesy Susan Dawson, University
of Liverpool.)
149
150
Fig 16-5 Cat with ulcerative keratitis caused by FHV-1 infection. (Courtesy Susan
Dawson, University of Liverpool.)
Fig 16-6 Two lingual ulcers on the tongue of a cat infected with FCV. (From
Gaskell RM, Radford AD, Dawson S. 2004. Feline infectious respiratory
disease, p 588. In Chandler EA, Gaskell CJ, Gaskell RM [eds], Feline
medicine and therapeutics, ed 3, Blackwell Publishing, Oxford. Used
with permission.)
Feline Calicivirus Infection
Strains of FCV can differ in tropism and virulence; therefore a wide range of clinical signs may be seen. Most
strains induce a fairly characteristic, mild syndrome characterized by pyrexia, oral ulceration, and mild
respiratory and conjunctival signs. Some strains of FCV, however, are nonpathogenic; others are more virulent
and may induce more severe systemic disease. Several outbreaks of a severe acute systemic febrile disease with
high mortality have been described, caused by particularly virulent strains of FCV.
23,43,66,84
In a typical case of FCV infection, early signs include depression and pyrexia, although cats typically stay
brighter than with FHV-1 infection. Oral ulceration is the most characteristic feature of FCV infection and may
be the only clinical sign present (Fig. 16-6). Ulceration is usually on the tongue but can occur elsewhere in the
mouth, on the lips, and on the nose. Skin ulceration on other parts of the body occurs rarely.
Sneezing, conjunctivitis, and ocular and nasal discharges typically occur but are generally much less prominent
compared with FHV-1 infection. Cats with oral ulcers may show hypersalivation with moisture on the fur
around the mouth, but generally, no drooling of saliva occurs. Some of the more virulent strains can cause
pneumonia with associated dyspnea.
Some FCV strains produce lameness and pyrexia.
27,100
The lameness may or may not be associated with oral
and respiratory signs, and it is likely that considerable overlap exists between the conditions.
99
Affected cats are
often dull and anorexic. In most cases, full recovery occurs within 24 to 48 hours, and so far, no evidence can
be found of any long-term effects on the joints. Acute lameness has also been observed after vaccination, and in
some of these cases, viruses originating from live vaccines may be involved.
71
Several outbreaks of the recently reported severe systemic syndrome have been described.
23,43,66,84
Affected
cats variably show facial and paw edema (approximately 50%), pyrexia (90%), classic signs of upper
respiratory infection (50%), icterus (20%) and hemorrhages from the nose and in the feces (30% to 40%).
Necropsy findings included pneumonia, hepatomegaly, pancreatitis, and pericarditis. Many of the affected cats
were fully vaccinated, suggesting that, as with more typical strains of FCV, vaccines may not completely
protect against these virulent systemic disease-producing isolates. The outbreaks were relatively well controlled
with strict quarantine and isolation, but given that FCV is an inherently variable pathogen, clinicians must
remain vigilant in the event of such viruses appearing again.
The chronic oral disease, lymphoplasmacytic gingivitis stomatitis complex (LPGS) has also been associated
with FCV infection. In some studies, more than 80% of cats with chronic oral disease have been found to shed
FCV compared with approximately 20% of controls,
27
but these figures probably depend on the criteria used to
select clinical cases.
98
FCV infection has been associated with acute faucitis,
80
and in one colony of cats
chronic stomatitis developed after the accidental introduction of FCV.
106
However, other agents, in particular
FIV, and various host factors appear to be involved in the condition, and the pathogenesis is not yet fully
understood (see Stomatitis, Chapter 89).
In naturally occurring disease, a wide range of clinical signs have been reported in cats infected with B.
bronchiseptica, varying from upper respiratory tract signs of sneezing, oculonasal discharge, and coughing to
16.4.2
16.4.3
severe dyspnea, cyanosis, and death caused by bronchopneumonia.
*
In general, coughing appears to be less
marked in cats than it is in dogs infected with B. bronchiseptica. Young kittens appear to be most susceptible to
disease, particularly bronchopneumonia.
In experimental studies using SPF cats, the main clinical signs of B. bronchiseptica infection were pyrexia,
lethargy, coughing, sneezing, oculonasal discharge, and submandibular lymphadenopathy, which resolved after
approximately 10 days.
12,42,44,109
* References 3, 15, 89, 101, 108.
DIAGNOSIS
Diagnosis may be attempted based on clinical signs alone. For example, predominantly oral ulceration might
indicate FCV, whereas marked sneezing with more severe respiratory and conjunctival signs might suggest FHV-1
(see Table 16-1). With Chlamydophila infection, the main clinical sign is a marked persistent conjunctivitis (see
Chapter 30).
Table 16-2 Therapy of Feline Respiratory Infections
DRUG
DOSE
a
ROUTE INTERVAL
(HOURS)
DURATION
(DAYS)
INDICATIONS
Idoxuridine (0.1% solution) One drop Topical in eye 46 21 FHV-1 ulcerative
keratitis
Interferon- 30 U PO 24
7
b
Acute respiratory and
ocular herpesvirus
infections
Interferon- (2550 U/ml
solution)
c
One drop Topical in eye 46 prn Ocular herpesvirus
infections
L-lysine 200500 mg PO 12 prn Acute and latent
FHV-1 infections
Tetracycline 1522 mg/kg
PO
d
8 1421 Bordetellosis,
Chlamydophila
infection
Doxycycline 5 mg/kg
PO
d
12 1421 Bordetellosis,
Chlamydophila
infection
Trimethoprim-sulfonamides15 mg/kg PO 12
714
e
Bordetellosis
Enrofloxacin 5 mg/kg PO 24
714
f
Bordetellosis,
Chlamydophila
infection
Phenylephrine 2.5%
solution
1 drop Topical in each
nostril
12 7 Nasal decongestion
FHV-1, Feline herpesvirus-1; U, units; PO, by mouth; prn, as needed.
a Dose per administration at specified interval. For additional information on antimicrobial drugs, see
Drug Formulary, Appendix 8.
b Drug is given on and off on 7 day cycles for an indefinite period.
c Note: use of IFN- topically has not been studied.
d Tetracyclines, especially as the hydrochloride salts, can cause esophagitis unless precautions are taken.
See Drug Formulary, Appendix 8.
150
151
16.5
e This drug can be myelosuppressive or have nephrotoxicity in cats. Monitoring of complete blood count
and renal function should be done with repeated or longer treatment intervals. See Drug Formulary,
Appendix 8.
f This drug can cause retinal toxicity and blindness in cats when used at higher doses or for longer
periods. See Drug Formulary, Appendix 8.
Confirmatory diagnosis of FHV-1 and FCV can be made from oropharyngeal or conjunctival swabs by virus
isolation in feline cell cultures, by immunofluorescence or enzyme-linked immunosorbent assay (ELISA)
techniques, or by PCR.
*
PCR is more sensitive than virus isolation is for detection of FHV-1, although the
significance of PCR-positive, isolation-negative cats are unclear. For FCV, reverse transcriptase polymerase chain
reaction is not currently routinely used for diagnosis, but PCR and sequencing are useful for distinguishing
between FCV isolates in investigating the epidemiology of the disease.
71,73-75,96
Serology is generally not helpful
in the diagnosis of FHV-1 and FCV infection because of widespread antibody from vaccination.
For diagnosis of B. bronchiseptica infection, oropharyngeal or nasal swabs should be taken and placed into
charcoal Amies transport medium (Beckton Dickenson, Cockeysville, Md.) before plating at the laboratory on
appropriate selective medium that prevents overgrowth by other respiratory flora.
89
Transtracheal wash specimens
can also be used for the isolation of B. bronchiseptica from clinical cases. Serology is not widely available, and
many healthy cats are seropositive in any case.
Diagnosis of C. felis infection is described in Chapter 30. C. felis infection should be considered when
conjunctivitis is the predominant clinical sign.
When an organism is isolated from an animal with respiratory disease, a reasonable assumption is that the agent
has been involved in the disease process. However, especially for FCV and Bordetella, a relatively large number
of clinically healthy cats will also be shedding the organisms. Isolation may therefore be a coincidental finding.
* References 36, 51, 71, 91, 92, 95, 97, 105, 107.
THERAPY
No antiviral drugs are in widespread use for the treatment of FHV-1 and FCV. Drugs such as acyclovir, given in
human herpesvirus infections, do not seem to have good activity against FHV-1, and others are either toxic or
awaiting evaluation.
63
However, in cases of ulcerative keratitis associated with FHV-1 infection, other antivirals
have been used with some success, largely based on their efficacy in human ocular herpesvirus infections.
11,90
See
Chapter 93 for further information of antiviral treatment of ocular viral infections. Interferon may also be useful
for cats with acute respiratory viral infections, and for ocular herpes infections, although evidence for its success is
limited.
61,90
Some data from both in vitro and in vivo studies suggest that orally administered lysine may be useful
in treating acutely and latently FHV-1-infected cats.
50,53,93
For FCV, ribavirin has been shown to be effective in
cell culture but was too toxic for in vivo use.
68,69
For additional information on the use of these drugs, see Table
16-2, Antiviral Chemotherapy, Chapter 2, and Drug Formulary, Appendix 8.
In viral respiratory disease, broad-spectrum antibiotic therapy should be given to help control secondary bacterial
infection. Because swallowing solid tablets may be painful for cats, antibiotics can be given as pediatric syrups or
long-acting injections. Cats should be reexamined after 4 to 5 days and, if necessary, bacterial culture and
susceptibility tests performed.
16.6
In vitro studies have suggested that tetracyclines, and in particular doxycycline with its longer half-life, are the
antibiotics of choice for the treatment of feline bordetellosis, although occasional resistance has been
observed.
24,88
However, limited experimental evidence suggests that treatment with doxycycline may not
eliminate the organism from the cat during the later stages of infection. Notably, systemic tetracyclines are
theoretically contraindicated in pregnant cats or young kittens in which dental development is occurring. This is
potentially less of a problem with doxycycline, although other side effects associated with its use may occur, such
as esophagitis.
58,59
Also see Drug Formulary, Appendix 8. Other antibacterials that have shown good in vitro
activity against B. bronchiseptica include trimethoprim-sulfamethoxazole and enrofloxacin.
9,24,88
Newer
erythromycin derivatives such as azithromycin and clarithromycin have been effective against human Bordetella
isolates
39
and might be effective against feline B. bronchiseptica that is resistant to the previously mentioned
antimicrobials. However, these are not licensed for feline use in European Union counties.
Good nursing care is essential in cases of feline respiratory disease and, in milder cases, is generally best given at
home by the owner. The cat should be encouraged to eat by offering strongly flavored aromatic foods. If eating is
painful, baby foods or specialized proprietary or blended food may be helpful. Severe cases may require
hospitalization and fluid therapy, and when anorexia is prolonged, a nasogastric or gastrotomy tube may be
indicated. Nasal decongestants (e.g., phenylephrine) in the acute phase and mucolytic drugs (e.g., bromhexine
hydrochloride) in the more chronic phase have been suggested to help clear airways, but conventional steam
inhalation (e.g., placing the cat in steamy room) or nebulizing saline may also be useful.
PREVENTION
Immunity
For both FHV-1 and FCV, immunity has generally been measured by serum virus neutralizing (VN) antibody
levels, although for FHV-1 cell-mediated immunity (CMI) is likely to be a better reflection of immune status.
VN antibody has always been considered the hallmark of immunity for FCV and is certainly important in
protection, as recent studies using mouse-cat chimeric antibodies have also shown.
102,103
However, some cats
with no detectable VN antibody have demonstrated immunity to rechallenge with a heterologous strain, and
several types of CMI responses have been reported.
27
For both viruses, local immune responses are also likely
to be important. The ultimate test of immunity is, of course, response to challenge.
In FHV-1 infection, just after the primary disease, cats are generally resistant to challenge, although VN
antibody titers are generally low and in some cases undetectable. After 6 months or more, protection may be
only partial, and indeed, carrier cats may develop recrudescent disease. After either reactivation or field
challenge, VN antibody titers rise to more moderate levels and thereafter remain reasonably stable, independent
of virus shedding episodes.
Most cats are protected following the use of modified live or inactivated FHV-1 vaccines. However, immunity
is not necessarily complete in all animals, even if challenge takes place within 3 months of the initial
vaccination.
28
Similar levels of protection have been reported after a year. More studies have shown that the
relative efficacy of an inactivated vaccine decreased from 83% shortly after primary vaccination to 52% after
7.5 years.
86
151
152
16.7
16.7.1
With FCV infection, VN antibody titers are higher than those in FHV-1, and immunity is generally longer
lived. However, some variation exists, depending on the virus strain involved and whether homologous or
heterologous protection is being considered. Reinfection with a second strain will generally boost responses to
both strains.
After vaccination against FCV, reasonable protection has been reported to last 10 to 12 months.
29
VN antibody
levels tend to be higher compared with those in FHV-1, and in general, a better correlation exists with
protection. In more studies, moderate levels of VN antibody have been shown to persist in a group of
vaccinated cats for at least 4 years, although after 7.5 years, titers had declined to low or nondetectable
levels.
85,86
Protection against a homologous FCV challenge decreased from 85% 3 weeks after vaccination to
63% after 7.5 years.
MDAs (i.e., essentially colostral) in kittens may persist for 2 to 10 weeks for FHV-1, with mean levels falling
below detectable levels (less than 1:2) by 9 weeks of age. For FCV, in most kittens, MDAs persist for 10 to 14
weeks. However, for both viruses, low levels of MDAs do not necessarily protect against subclinical infection.
Interestingly, some animals with no detectable FHV-1 antibody appeared to be protected against disease but not
infection.
Studies on immunity in B. bronchiseptica infection have concentrated on the measurement of IgG levels in
serum as measured by ELISA. After primary infection, antibody levels rise by 4 weeks to reasonably high
titers. Experimental studies with an intranasal (IN) feline B. bronchiseptica vaccine showed that protection
against challenge was present within 72 hours of vaccination and lasted for at least a year.
109
MDAs for
Bordetella have been detected in experimental cats, although these appear to be fairly short lived, lasting for
only 2 to 6 weeks.
27
Vaccination
Vaccination has been available for many years against the two respiratory viruses and has been relatively
successful in controlling disease. However, disease can still be a problem, especially when cats are kept
grouped together and when kittens lose their MDAs before vaccination. Both viruses are very widespread in the
cat population and carriers are common, ensuring plenty of exposure. Prevention and control therefore often
require a combined approach of vaccination and management.
Three types of FHV-1 and FCV vaccines are commercially available: modified live virus (MLV) vaccines
administered parenterally or IN and inactivated adjuvanted virus vaccines given parenterally. In addition, a
significant number of genetically engineered vaccines for both FHV-1 and FCV have been reported.
For routine FHV-1 and FCV vaccination programs, all types of vaccine appear to be suitable. In previously
unexposed cats, all vaccines induce reasonable protection against disease but generally do not protect against
infection or the development of the carrier state.
Several FCV strains are used in commercial vaccines, including strains F9 and 255. Most of these strains seem
to protect against the majority of FCV isolates but not as well against all. Some evidence suggests that
multivalent vaccines may increase the proportion of strains neutralized.
38
Parenteral MLV vaccines should be administered carefully because clinical signs can be induced if the vaccine
virus reaches the oral-respiratory mucosa (i.e., if the cat licks the injection site or if an aerosol is made with the
16.7.2
syringe). Vaccine virus should not generalize, but spread of the MLV-FCV component within the cat after
parenteral inoculation may sometimes occur, possibly leading to disease in the individual cat and possibly
spreading to other cats.
67,71
However, genetic typing has shown that, although some cases of disease following
vaccination may be caused by the vaccine virus, the majority are associated with coincidental field virus
infection.
71,73
IN-MLV vaccine induces better protection but often induces slight side effects, such as sneezing and ocular and
nasal discharges. IN vaccines, however, are useful for rapid (2 to 4 days) onset of protection. IN vaccines used
in conjunction with parenteral vaccine on entry have reduced the severity of upper respiratory disease in cats
maintained at contaminated shelters for 3 or more days.
19
Inactivated adjuvanted vaccines can be reasonably effective, and modern adjuvants have led to improvements in
immunogenicity (see Chapter 100). However, adjuvants can sometimes cause local or systemic reactions. Very
rarely, feline vaccineassociated sarcomas may develop at the site of injection, particularly following the use of
aluminium-based adjuvants.
28,49,62
Inactivated vaccines are helpful in virus-free colonies because no risk of
spread or reversion to virulence is present. Some inactivated vaccines are licensed for use in pregnant queens,
and vaccination during pregnancy can help protect kittens by prolonging MDAs.
Boosters for FCV and FHV-1 vaccines are traditionally recommended every year, although evidence indicates
that immunity may last longer in some cases.
85,86
In view of this finding, and because of concerns over vaccine
site reactions, it has been suggested that after the first annual booster, revaccination intervals may be extended
up to 3 years.
21,22
In addition, an individual risk-benefit assessment is proposed to determine the most
appropriate vaccination strategy for a particular animal.
28,29
For B. bronchiseptica, an IN-MLV vaccine is available, which has been shown to have a duration of immunity
of at least a year.
109
The vaccine is similar to IN products available for dogs. Mild respiratory signs such as
sneezing and nasal discharge may occur following vaccination, as for the IN viral vaccines. The vaccine is
indicated in cases in which cats are at specific risk of acquiring Bordetella infection, for example, in rescue
shelters or boarding catteries, or where bordetellosis is known to be a problem.
An inactivated, fimbrial subunitbased vaccine has also been marketed in some countries, but the IN vaccine
will likely replace this.
Disease Control
The following measures apply in general to both viral respiratory disease and B. bronchiseptica infection.
Routine vaccination for the respiratory viruses is indicated, but B. bronchiseptica vaccination is probably best
recommended primarily for high-risk situations, such as in boarding and shelter facilities. The possibility of
transmission of B. bronchiseptica between dogs and cats should also be considered.
Household Cats
Pets should be vaccinated regularly. If the cat goes into a boarding cattery or other high-risk situations, it
should be boosted every year. From the point of view of infectious disease, ideally, a friend or neighbor
should feed the cat while the owner is on vacation. Individual cats should be protected from stress and social
contact as much as possible to avoid exposure.
152
153
16.7.3
16.7.3.1
Boarding Catteries
All cats entering the cattery should have an up-to-date vaccination record, with annual boosters. When rapid
protection is required, IN vaccine may be given. Clients should be aware that such vaccines themselves may
induce mild clinical signs.
Cattery owners should not rely on vaccination alone for disease control because pathogens will inevitably be
present either from the occasional cat incubating disease or from carriers. Thus measures should be taken to
prevent spread of infection and reduce the concentration of infectious agents in the environment (Table
16-3). Such measures may appear complicated, but in practice, they are not difficult to implement and, in the
authors' (RG, SD, AR) experience, can actually increase the efficiency within a cattery.
Shelter Facilities
In general, the same management measures apply as those with boarding catteries. Although this practice
may be more difficult to achieve, molecular typing studies have demonstrated that limiting the spread of
individual FCV isolates within a shelter is possible if good hygiene measures are used.
74
Because the
immune status of the cats in a rescue shelter is often unknown, incoming animals should be quarantined and
isolated from others. Those with clinical signs should be kept apart. Unless animals can be isolated on arrival
for 3 to 4 weeks, parenteral vaccines may not have time to become effective. In these circumstances, using
the IN vaccines may be advisable if available. Infected dogs, which can act as a source of B. bronchiseptica
infection in cats, should be housed separately where possible, especially if an outbreak of canine infectious
tracheobronchitis occurs.
Breeding Catteries
In disease-free colonies, cats should be vaccinated regularly if any contact, direct or indirect, occurs with
other cats. Inactivated vaccines are preferable. Care should be taken to avoid bringing virus into the colony;
any cat with a history of or contact with oral or respiratory disease may be a carrier. Vaccinated cats can be
carriers, and kittens can be infected subclinically because of MDAs. Thus stud cats and new breeding stock
should be from a respiratory diseasefree colony. The risk of infection from cat shows is possible, but the
greatest risk of infection to disease-free households is from stud cats and new breeding stock when exposure
is prolonged.
16.7.3.2
16.7.3.3
16.7.3.4
Table 16-3 Recommendations to Prevent the Spread of the Respiratory
Viruses in a Boarding Cattery
Admit only fully vaccinated cats.
House cats individually with solid partitions between pens, unless cats are from same household.
Ensure that frontages are at least 1 meter apart.
Put known carriers or cats with history of respiratory disease in a separate section or at least at one end of the cattery;
and feed last.
Ensure that surfaces of pen are easily washable and that food and litter bowls can be easily removed without entering
the pen (i.e., do not handle cats more than necessary).
Feed cats in same order each day and attend to each pen completely before moving on to the next.
Either disinfect hands between each pen or have individual rubber gloves for each pen, for use only with that pen.
Disinfect gloves thoroughly before use with a new boarder. Alternatively use disposable gloves.
Wear rubber boots and step into a disinfectant bath if it is necessary to enter a pen.
Either use disposable food trays or have two sets of food bowls used on alternate days. Soak used set in a 1:32 bleach
solution with detergent for several hours and then rinse and allow to dry until reuse 24 hours later.
Prepare food in a central area.
Use similar system to food bowls for litter trays.
When a cat goes home, thoroughly disinfect cage, allow to dry, and preferably leave empty for 2 days before reusing.
Reduce concentration of virus in the environment by providing adequate ventilation, low relative humidity, and
optimal environmental temperatures.
Adapted from Gaskell RM, Radford AD, Dawson S. 2004. Feline infectious respiratory disease, p 590. In Chandler EA,
Gaskell CJ, Gaskell RM (eds), Feline medicine and therapeutics, ed 3, Blackwell Publishing, Oxford. Used with permission.
153
Table 16-4 Feline Respiratory Disease Control Program in a Breeding Cattery
with Endemic Disease
Provide regular vaccination programs.
Give booster vaccinations to queens either before mating or during pregnancy (inactivated vaccine only).
Keep cats as stress free as possible, and use good management practices to reduce spread of viruses within the colony.
Avoid breeding from queens with a history of oral or respiratory disease in their kittens.
Move queens into isolation at least 3 weeks before term so that the kittens are not exposed to carriers in the colony
and that any shedding episode from the queen, as a result of the move, will end before parturition.
Wean kittens into isolation away from the queen as soon as feasible (ideally at 4 to 5 weeks before MDAs wane if it is
likely she is a carrier).
Vaccinate all kittens as soon as MDAs are at a noninterfering level (normally 9 or more weeks), and keep them in strict
isolation until a week after the second dose (normally at 12 weeks).
Earlier FHV-1 and FCV vaccination schedules with IN or parenteral vaccines may be used, although these are not
always licensed for early use and should be used with care. Parenteral vaccines can be given from 6 weeks of age, at 3
week intervals until 12 weeks of age. IN vaccination should be carried out 7 to 10 days or so before disease has been
occurring and then again at 12 weeks. Some evidence indicates that multiple doses are not necessary, although they
were originally advocated.
MDAs, Maternally derived antibodies; FHV-1, feline herpesvirus-1; FCV, feline calicivirus; IN, intranasal.
Cats entering the disease-free colony should be quarantined for 3 weeks to identify animals incubating the
disease. Cats should be swabbed for virus detection at least twice a week during this time. This practice
increases the probability of detecting FHV-1 excretion and low-level shedding FCV carriers. Even so, the
risk still exists of importing a latent FHV-1 carrier or a low-level FCV carrier that may be a source of
infection. Oropharyngeal swabs may also be tested for B. bronchiseptica infection.
In breeding colonies where the disease is endemic, achieving or maintaining virus-free or Bordetella-free
status is difficult. For both respiratory viruses and B. bronchiseptica, carriers are common providing a
frequent source of infection. For most situations, the only reasonable course is to attempt disease control
(Table 16-4).
Suggested Readings
*
* See the CD-ROM for a complete list of references.
3. Binns, SH, Dawson, S, Speakman, AJ, et al.: Prevalence and risk factors for feline Bordetella
bronchiseptica infection. Vet Rec. 144, 1999, 575580.
21. Elston, T, Rodan, H, Flemming, D, et al.: 1998 report of the American Association of Feline
Practitioners and Academy of Feline Medicine Advisory Panel on Feline Vaccines. J Am Vet Med Assoc.
212, 1998, 227241.
29. Gaskell, RM, Gettinby, G, Graham, SJ, et al.: Veterinary Products Committee working group report on
feline and canine vaccination. Vet Rec. 150, 2002, 126134.
153
154
16.8
43. Hurley, KF, Pesavento, PA, Pedersen, NC, et al.: An outbreak of virulent systemic feline calicivirus
disease. J Am Vet Med Assoc. 224, 2004, 241249.
51. Maggs, DJ, Lappin, MR, Nasisse, MP: Detection of feline herpesvirus-specific antibodies and DNA in
aqueous humor from cats with or without uveitis. Am J Vet Res. 60, 1999, 932936.
66. Pedersen, NC, Elliott, JB, Glasgow, A, et al.: An isolated epizootic of hemorrhagic-like fever in cats
caused by a novel and highly virulent strain of feline calicivirus. Vet Microbiol. 73, 2000, 281300.
75. Radford, AD, Sommerville, L, Ryvar, R, et al.: Endemic infection of a cat colony with a feline
calicivirus closely related to an isolate used in live attenuated vaccines. Vaccine. 19, 2001, 43584362.
86. Scott, FW, Geissinger, CM: Long-term immunity in cats vaccinated with an inactivated trivalent
vaccine. Am J Vet Res. 60, 1999, 652658.
Uncited references
17. Dawson, S, Willoughby, K, Gaskell, RM, et al.: A field trial to assess the effect of vaccination against
feline herpesvirus, feline calicivirus and feline panleukopenia virus in 6-week-old kittens. J Feline Med
Surg. 3, 2001, 1722.
16.9

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CHAPTER 16 Feline Respiratory Disease

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