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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 diseasethan FCV does, but FCV appears to be relatively more common.

7,27,60This 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 thatBordetella bronchisepticais 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 psittacivar. 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 showreduced 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.

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Feline Calicivirus

FCV is a small, unenveloped, single-stranded RNA virus, a member of the Vesivirusgenus 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. bronchisepticais 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. bronchisepticawas 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 inBordetella-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 forB. bronchisepticainfection in cats have been identified in epidemiologic

studies.3

References 41, 48, 89, 101, 108

Other Organisms

C. feliscauses acute to chronic conjunctivitis in cats, although respiratory signs may also be seen. The

prevalence of C. felisin cats with conjunctival or upper respiratory tract disease has been reported in studies

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using polymerase chain reaction (PCR) to range between 14.3%94

and 59%.7The 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 havebeen isolated in pure culture from cases of bronchopneumonia, which have responded to antimycoplasmal

therapy.25

Other bacteria such as Staphylococcusspp., Streptococcusspp.,Pasteurella multocida,and

Escherichia coliare 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 acattery, 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

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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 75days, 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

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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 andtherapeutics, ed 3, Blackwell Publishing, Oxford. Used with permission.)

B. bronchiseptica Infection

Serosurveys have shown thatB. bronchisepticais 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 sheddingB. bronchisepticafrom the oropharynx, with a

higher positive number in rescue catteries and in households with larger numbers of cats.3An association

betweenB. bronchisepticainfection 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.

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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 forB.

bronchisepticainfection in cats.3In 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, andB. bronchisepticaisolated from all four animals were found to be the same using

PFGE.15

Interestingly, Foley and colleagues24

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 withBordetellainfection, with 9% of

clinically healthy cats shedding the organism.3Experimental work has shown thatB. bronchisepticais shed in

both oropharyngeal and nasal secretions, in some cases for at least 19 weeks after infection.12

In the same

study,B. bronchisepticawas 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

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Fig 16-2 FCV carrier state: epidemiology. (Flow diagram from Gaskell RM,

Radford AD, Dawson S. 2004. Feline infectious respiratory disease, p

584. InChandler EA, Gaskell CJ, Gaskell RM [eds], Feline medicine andtherapeutics,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.

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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 withB. bronchisepticaappears 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 fromB. bronchisepticafollowing 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.

AlthoughB. bronchisepticamay 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

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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 FCVa 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,33,34,62aand 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

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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. InChandler 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.)

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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. InChandler EA, Gaskell CJ, Gaskell RM [eds], Feline

medicine and therapeutics, ed 3, Blackwell Publishing, Oxford. Used

with permission.)



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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 causepneumonia 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 catswere 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 withB.

bronchiseptica,varying from upper respiratory tract signs of sneezing, oculonasal discharge, and coughing to

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severe dyspnea, cyanosis, and death caused by bronchopneumonia.*In general, coughing appears to be less

marked in cats than it is in dogs infected withB. bronchiseptica. Young kittens appear to be most susceptible to

disease, particularly bronchopneumonia.

In experimental studies using SPF cats, the main clinical signs ofB. bronchisepticainfection 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 Chlamydophilainfection, the main clinical sign is a marked persistent conjunctivitis (see

Chapter 30).

Table 16-2 Therapy of Feline Respiratory Infections

DRUG DOSEa 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 7b 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/kgPO

d 8 1421 Bordetellosis,

Chlamydophila

infection

Doxycycline 5 mg/kg POd 12 1421 Bordetellosis,

Chlamydophila

infection

Trimethoprim-sulfonamides15 mg/kg PO 12 714e Bordetellosis

Enrofloxacin 5 mg/kg PO 24 714f 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.

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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 longerperiods. 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 ofB. bronchisepticainfection, 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 ofB. bronchisepticafrom clinical cases. Serology is not widely available, and

many healthy cats are seropositive in any case.

Diagnosis of C. felisinfection is described in Chapter 30. C. felisinfection 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 andBordetella,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 93for 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.

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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 againstB. bronchisepticainclude trimethoprim-sulfamethoxazole and enrofloxacin.9,24,88

Newer

erythromycin derivatives such as azithromycin and clarithromycin have been effective against humanBordetella

isolates39

and might be effective against felineB. bronchisepticathat 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 initialvaccination.

28Similar 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

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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 notinfection.

Studies on immunity inB. bronchisepticainfection 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) felineB. bronchisepticavaccine showed that protection

against challenge was present within 72 hours of vaccination and lasted for at least a year.109

MDAs for

Bordetellahave 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

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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

ForB. 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 acquiringBordetellainfection, 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 andB. bronchisepticainfection.

Routine vaccination for the respiratory viruses is indicated, butB. bronchisepticavaccination is probably best

recommended primarily for high-risk situations, such as in boarding and shelter facilities. The possibility of

transmission ofB. bronchisepticabetween 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

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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 ofB. 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.

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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



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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 strictisolation 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 forB. bronchisepticainfection.

In breeding colonies where the disease is endemic, achieving or maintaining virus-free orBordetella-free

status is difficult. For both respiratory viruses andB. 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 felineBordetella

bronchisepticainfection. 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.

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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 MedSurg. 3, 2001, 1722.

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