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Feline herpesvirus infection

Virus

Feline herpesvirus (FHV), the agent of feline viral rhinotracheitis, is distributed

worldwide. The virus belongs to the order Herpesvirales, family Herpesviridae,

subfamily Alphaherpesvirinae, genus Varicellovirus. Although only one serotype

is described, the virulence can differ between viral strains (Gaskell et al., 2007);

differences can also be observed by restriction endonuclease analysis (Hamano

et al., 2004; Thiry, 2006).

The genomic double-stranded DNA of FHV is packaged into an icosahedral capsid

surrounded by a proteinaceous tegument and a phospholipid envelope, which

contains at least ten glycoproteins. In the feline host, FHV replicates in epithelial

cells of both the conjunctiva and the upper respiratory tract, and in neurons. The

neuronal infection enables the virus to establish lifelong latency after primary

infection. FHV is related antigenically to canine herpesvirus and phocid

herpesviruses 1 and 2; there is no known cross-species transfer (Gaskell et al.,

2006).

The virus is inactivated within 3 hours at 37°C and is susceptible to most

commercial disinfectants, antiseptics and detergents. At 4°C, it remains infectious

for about five months, at 25°C for about one month, and it is inactivated at 56°C in

4-5 minutes (Pedersen, 1987).

Epidemiology

The domestic cat is the main host of FHV, but it has been isolated also from

other felids, including cheetahs and lions, and antibodies have been detected

in pumas. There is no evidence of human infection.

Latent chronic infection is the typical outcome of an acute infection, and

intermittent reactivation gives rise to viral shedding in oronasal and conjunctival

secretions. Except in catteries, contamination of the environment is not important

for virus transmission. Virus shedding by acutely infected cats as well as by

latently infected cats experiencing reactivation are the two main sources of

ABCD_feline herpesvirus infection_V3_2015

infection (Gaskell and Povey, 1982).

Transplacental infection has not been seen in the field. Latently infected queens

may transmit FHV to their offspring because parturition and lactation are stressful

events leading to viral reactivation and shedding. Kittens may therefore acquire

FHV infection at an early age, before vaccination. The outcome of the infection

depends on MDA: when high levels are present, kittens are protected against

disease, experience a subclinical infection that leads to virus latency, whereas in

the absence of sufficient MDA, clinical manifestations may follow (Gaskell and

Povey, 1982).

In healthy small populations, the prevalence of viral shedding may be less than

1%, whereas in large populations, especially with clinical signs present, up to 20%

of the cats may shed (Coutts et al., 1994; Binns et al., 2000; Helps et al., 2005). In

shelters, the risk is higher: with 4% of shedders entering the shelter, after one

week, 50% of the cats may excrete the virus (Pedersen et al., 2004). The low

initial prevalence is likely to reflect the intermittent nature of viral shedding during

latency.

Pathogenesis

The virus enters via the nasal, oral or conjunctival routes. It causes a lytic infection

of the nasal epithelium with spread to the conjunctival sac, pharynx, trachea,

bronchi and bronchioles. Lesions are characterised by multifocal necrosis of

epithelium, with neutrophile granulocyte infiltration and inflammation. A transient

viraemia associated with blood mononuclear cells is observed after natural

infection in young cats (Westermeyer et al., 2009). This has been observed

exceptionally also in neonates (Gaskell et al., 2007).

Viral excretion starts as soon as 24 hours after infection and lasts for 1 to 3 weeks.

Acute disease resolves within 10 to 14 days. Some animals may develop chronic

lesions in the upper respiratory tract and ocular tissues.

Upon infection, the virus spreads along the sensory nerves and reaches

neurons, particularly in the trigeminal ganglia, which are the main sites of latency.

Almost all cats experiencing primary infection become lifelong latent carriers.

There are no direct diagnostic methods to identify latency, because the virus


persists as genomic DNA in the nucleus of the latently infected neurons, without

replication. Virus shedding can be induced experimentally in approximately 70%

of latently infected cats by glucocorticoid treatment. Other reactivating stressful

events include lactation (40 %), and moving the cat into a new environment

(18%) (Gaskell and Povey, 1977; Ellis, 1981; Gaskell and Povey, 1982;

Pedersen et al., 2004).

Some adult cats show acute lesions at the time of viral reactivation;

disease ensuing reactivation is referred to as recrudescence.

Conjunctivitis may be associated with corneal ulcers, which may develop into

chronic sequestra. Stromal keratitis is a secondary, immune-mediated reaction

due to the presence of virus in the epithelium or stroma. Damage to the nasal

turbinates during acute disease is thought to be a predisposing factor for chronic

rhinitis (Gaskell et al., 2007).

Immunity

Passive immunity acquired via colostrum

During their first weeks of life, kittens are protected against infectious disease by

MDA, but in FHV infection, antibody levels are generally low. They may persist

for 10 weeks (Johnson and Povey, 1985), but may have vanished already at 6

weeks of age (in about 25% of kittens; Dawson et al., 2001).

Active immune response

Glycoproteins embedded in the herpesvirus envelope are important in the

induction of immunity; after infection, the detection of virus neutralizing antibodies

(VNA) correlates with the recognition of FHV glycoproteins (Burgener and Maes,

1988). Furthermore, immunisation of rabbits with the FHV membrane protein gD

led to the production of high VNA titres (Spatz et al., 1994).

Natural FHV infection does not result in a comprehensive immunity; in general,

the immune response protects against disease but not against infection, and after

re-infection, mild clinical signs have been observed only 150 days after primary

infection (Gaskell and Povey, 1979). VNA titres after natural infection are often


low and rise slowly - indeed, they may still be absent after 40 days (Gaskell and

Povey, 1979). VNA most likely contribute to the protection against acute infection.

Other antibody-mediated mechanisms e.g. antibody mediated cellular cytotoxicity

(ADCC) and antibody-induced complement lysis have been demonstrated

(Wardley et al., 1976). As in other alphaherpesvirus infections, cell-mediated

immunity plays an important role in protection, since the absence of serum

antibody in vaccinated cats does not mean that cats will develop disease; on the

other hand, seroconversion did correlate with protection against a virulent FHV

challenge (Lappin et al., 2002).

Although antibody presence and protection against clinical signs are

correlated, there is currently no test available that predicts the degree of

protection in individual cats.

Since FHV is a pathogen of the respiratory tract, mucosal cellular and humoral

responses are important. Studies with intranasal vaccines have shown clinical

benefits as early as 2-6 days after vaccination (Slater and York, 1976; Weigler et

al., 1997b; Lappin et al., 2006).

Clinical signs

Table 1. FHV disease, lesions and clinical signs

[Note: Exclusion of concurrent infection with other agents is required to determine

the FHV aetiology of chronic rhinitis]

Disease type Pathology Main clinical manifestations

Classical acute disease

(cytolytic disease)

Rhinitis, conjunctivitis,

superficial and deep corneal

ulcers, in particular dendritic

ulcers

Sneezing, nasal

discharge, conjunctival

hyperaemia and serous

discharge


Atypical acute disease Dermatitis

Viraemia, pneumonia

Nasal and facial ulcerated

and crust forming lesions

Severe systemic signs,

coughing, death (acute

death in kittens, “fading

kitten syndrome”)

Chronic disease

(immune-mediated

disease)

Stromal keratitis

Chronic rhinosinusitis

Corneal oedema,

vascularisation,

blindness

Chronic sneezing and

nasal discharge

Possibly FHV-

related diseases

Corneal sequestra

Eosinophilic keratitis

Neurological disease

Uveitis

FHV infection typically causes acute upper respiratory and ocular disease, which

is particularly severe in young kittens. Viral replication causes the erosion and

ulceration of mucosal surfaces, resulting in rhinitis, conjunctivitis, and

occasionally corneal ulcerative disease; dendritic ulcers are considered a

pathognomonic manifestation (Maggs, 2005). FHV is the most important cause

of corneal ulceration (Hartley, 2010).

Typical clinical signs start with salivation, sneezing and coughing, followed by

pyrexia, depression and anorexia, serous or sero-sanguineous ocular and/or

nasal discharge, and conjunctival hyperaemia (Gaskell et al., 2006). Secondary

bacterial infection is common, in which case secretions become purulent.

Occasionally, primary pneumonia and a viraemic state are seen, with severe

generalized signs and a fatal outcome (Gaskell et al., 2006).


Less frequently, oral ulceration, dermatitis, skin ulcers (Hargis and Ginn, 1999)

and neurological signs (Gaskell et al., 2006) occur. Abortion is a rare secondary

effect, which is not a direct consequence of viral replication - in contrast to

herpesvirus infections in other species.

After reactivation and recrudescence, cats may show acute cytolytic disease as

described above. Others may present with chronic ocular immune-mediated

disease in response to the presence of FHV antigen. Experimental infections

resulting in stromal keratitis with corneal oedema, inflammatory cell infiltrates,

vascularisation and eventually blindness suggest this pathogenetic mechanism

(Nasisse et al., 1989; Maggs, 2005).

Corneal sequestra and eosinophilic keratitis have been linked to the presence of

FHV in the cornea and/or blood. However, a definite causal association cannot be

made since some affected cats are FHV-negative (Nasisse et al., 1998; Cullen et

al., 2005). Viral DNA has been detected in the aqueous humour of a larger

proportion of cats suffering from uveitis as compared to healthy cats, suggesting

that FHV may play a role in the inflammation (Maggs et al., 1999b).

Chronic rhinosinusitis, a frequent cause of sneezing and nasal discharge, has

also been associated with the infection; however, viral DNA is detected only in

some affected cats, and also in healthy controls (Henderson et al., 2004). No

FHV replication is seen, which suggests that the virus might only initiate the

condition, which is then perpetuated by immune-mediated mechanisms like

inflammatory and remodelling phenomena, leading to permanent destruction of

nasal turbinates and bone, and complicated by secondary bacterial infection

(Johnson et al., 2005).

FHV infection often occurs in combination with feline calicivirus and/or Chlamydia

felis, Bordetella bronchiseptica, Mycoplasma spp. Other microorganisms, including

Staphylococcus spp. and Escherichia coli may lead to secondary infection of the

respiratory tract, causing a multi-agent respiratory syndrome (Gaskell et al., 2006).

Diagnosis

Methods for detecting FHV


The preferred method to detect FHV in biological samples is PCR, but virus

isolation is still used in several laboratories. The sensitivity and specificity of the

tests, especially of PCR, differ depending on the laboratory because of a lack of

standardisation.

The PCR variants currently used to detect FHV DNA in conjunctival, corneal or

oropharyngeal swabs, corneal scrapings, aqueous humour, corneal sequestra,

blood or biopsy specimens include conventional PCR, nested PCR and real-time

PCR (Hara et al., 1996; Nasisse and Weigler, 1997; Stiles et al., 1997a, 1997b;

Weigler et al., 1997a; Maggs et al., 1999a; Sykes et al., 2001; Vögtlin et al., 2002;

Helps et al., 2003; Marsilio et al., 2004). Most PCR primers are based on the

highly conserved thymidine kinase gene.

Molecular diagnostic methods are more sensitive than virus isolation or indirect

immunofluorescence (Reubel et al., 1993; Stiles et al., 1997b; Weigler et al.,

1997a; Burgesser et al., 1999; EBM grade I).

Because of the minute amounts of viral nucleic acid detectable by PCR, positive

test results should be interpreted with caution – they may not prove any

association with the disease. The sensitivity of PCR depends on the test format

(Maggs and Clarke, 2005); the system should include a control to measure feline

DNA, to estimate the quantity of material on the swab, and to check for inhibitory

substances. Due to its high sensitivity, PCR may also detect viral DNA in

scrapings of the cornea and/or tonsils suggesting non-productive infection (Reubel

et al., 1993; Stiles et al., 1997a; Maggs et al., 1999b). Consequently, its diagnostic

value for clinical infection may be poor, depending on the test sensitivity, the

samples analysed (biopsies and corneal scrapings yield positive results more

frequently than conjunctival samples) and the population tested (e.g. shelter cats

are more likely to test positive than household cats).

Additionally, PCR tests can detect FHV DNA in modified-live virus vaccines

(Maggs and Clarke, 2005); it is unknown if vaccinal strains are detected in

recently vaccinated animals and for how long after vaccination.

A positive PCR result may indicate low level shedding or viral latency and does not

mean that the virus is responsible for the observed clinical signs, although it

indicates the possibility of recurring signs in the future. However, when quantitative


real-time PCR is used (Vögtlin et al., 2002; EBM grade II), the amount of virus

measured may provide additional information on the etiological importance of the

agent: when high viral loads are present in the nasal secretion or tears, this

suggests active replication and involvement of the virus in the clinical signs. If low

copy numbers are detected in corneal scrapings, this would indicate a latent

infection.

When considering molecular diagnosis in clinical practice, the use of fluorescein

and topical anaesthetics should be avoided, because these compounds may affect

PCR sensitivity (Gould, 2011). It is advisable to contact the diagnostic laboratory in

advance for details of sample collection and shipping, which is mostly done with

regular mail at ambient temperature (Maggs, 2005). Using the same sample, PCR

allows the simultaneous detection of other feline pathogens frequently implicated

in respiratory and ocular diseases, especially Chlamydia felis and, less reliably,

feline calicivirus (Helps et al., 2003; Marsilio et al., 2004).

Virus isolation (VI) is an alternative method of diagnosing FHV infection. It is less

sensitive than PCR but does indicate that viable virus, not just DNA, is present.

In cats undergoing primary FHV infection, the virus can be detected by isolation

from conjunctival, nasal or pharyngeal swabs or scrapings, or from post-mortem

lung samples. In chronic infections, VI may be difficult.

Asymptomatic FHV carriers can be detected by VI, but both the positive and

negative predictive value of VI is low (Gaskell and Povey, 1977; Maggs et al.,

1999b). Samples must be collected before application of fluorescein or Rose

Bengal stain, which inhibit viral replication in cell culture (Brooks et al., 1994;

Storey et al., 2002). Also, clinical specimens must be sent quickly to the

laboratory, and refrigerated during shipping. For these logistic reasons and

despite its good sensitivity in acute disease, VI is not routinely used for FHV

infection diagnosis.

FHV-specific antigen can be detected by immunofluorescence assay (IFA) on

conjunctival or corneal smears or biopsy specimens. As for VI, the use of

fluorescein should be avoided before sampling, which may give false-positive

results and make test interpretation difficult. IFA is less sensitive than VI or PCR,

especially in chronic infections (Nasisse et al., 1993; Burgesser et al., 1999). No


correlation between VI and IFA has been observed, but a combination of both

methods may diagnose the presence of FHV better than either test alone (Nasisse

et al., 1993; Maggs et al., 1999b). Because of its low sensitivity and the

interference with fluorescein, often used in ophthalmology practice, IFA is not the

most suitable diagnostic test in chronic ocular disease (Nasisse et al., 1993).

Serology

Antibodies to FHV can be detected by neutralization test or ELISA in serum,

aqueous humour and cerebrospinal fluid (Dawson et al., 1998; Maggs et al.,

1999b). Due to natural infection and vaccination, seroprevalence is high, and the

demonstration of specific antibodies consequently does not correlate with disease

and active infection (Maggs et al., 1999b; EBM grade I).

Moreover, antibody detection does not allow differentiation between infected and

vaccinated animals, neutralizing antibodies are undetectable until 20 to 30 days

after a primary infection, and titres may be low, both in animals with acute and

chronic disease. Consequently serology is of limited value in the diagnosis of feline

herpesvirus infection (Nasisse and Weigler, 1997; Maggs et al., 1999b; Maggs,

2005).

Disease management

Supportive treatment

The restoration of fluids, electrolytes and the acid-base balance (e.g. replacement

of losses of potassium and bicarbonate due to salivation and reduced food

intake), preferably by intravenous administration, is required in cats with severe

clinical signs. Food intake is extremely important. Many sick cats do not eat

because of their loss of smell due to nasal congestion, or because of ulcers in the

oral cavity. Food may be blended to cause less pain when eating, should be

highly palatable, and may be warmed up to increase the smell. Appetite stimulants

(e.g. cyproheptadine) may be used. If the cat has not eaten for three days,

placement of a nasal or oesophageal feeding tube is indicated.

To prevent bacterial infection, antibiotics should be given in all acute cases of


feline upper respiratory tract disease, preferably broad-spectrum products with

good penetration in the respiratory tract.

Severely affected cats need intensive nursing care and appropriate supportive

therapy. Nasal discharge should be cleaned away several times a day using

physiologic saline solution, and local ointment applied. Drugs with mucolytic

effects (e.g. bromhexine) may be helpful. Eye drops or ointment can be

administered several times a day. Nebulisation of saline can be used to take care

of dehydration of the airways.

Vitamins are used, but their value is unproven.

Table 2. Symptomatic treatment for acute respiratory disease

Drug Comment ABCD recommendation EBMlevel

Topical treatmentnasal flushing with

physiological saline

solution and nebulization

to clean nasal discharge

and to prevent dehydration

of the upper airways

recommended several times daily 4

highly palatable food to ensure sufficient

food intake

necessary, if cats do not eat because of

pyrexia and/or ulcers in the oral cavity, or

because of their loss of smell due to nasal

congestion; food can be blended and

warmed up to increase smell

4

placement of a feeding

tube and enteral nutrition

to ensure sufficient

food intake

necessary if the cat has not been

eating for three days

4

Systemic treatmentFluid therapy to control dehydration

and restore electrolyte

and acid base imbalance

necessary in cats with severe clinical signs 4

Antibiotics to control secondary

bacterial infections

broad-spectrum antibiotics with good

penetration in the respiratory tract are

recommended for cats with severe

disease

4

Non-steroidal anti-

inflammatory drugs

to decrease fever recommended if cat is severely depressed 4

Drugs with mucolytic effects

(e.g., bromhexine)

to improve mucous

nasal discharge

may be helpful 4


Table 3. Symptomatic treatment for acute ocular disease (conjunctivitis and

keratitis)

Drug Comment ABCD recommendation EBMlevel

Antibiotics to control secondary

bacterial infections

Topical antibiotics 4

Anti-inflammatory drugs To decrease local

inflammation

Usually not needed; to avoid corticosteroids 4

Antiviral therapy

Table 4. Antiviral drugs recommended for topical and systemic treatment of acute

FHV

ocular disease. The drugs are listed in decreasing order of preference.

Topical treatmentDrug Type of drug Route of

administrationEfficacy

in vitro

Efficacy

in vivo

Controlled study in vivo?

Comments EBM

level

Trifluridine Nucleoside

analogue

Topical

Use every hour

for 1st day and

every 4 hours

thereafter

(Maggs, 2001)

Excellent n.d. no Topical treatment of

choice in ocular FHV

manifestations. Some

cats averse to topical

application. Toxic if

given systemically

(Maggs,

2001)

3

Cidofovir Nucleoside

analogue

0.5% solution

applied topically

yes yes yes Topical treatment for

ocular FHV; potent

drug with only two

daily applications

(Fontenelle et al.,

2008; Maggs, 2010)

3

Idoxuridine Nucleoside

analogue

Topical

use initially every

2-4 hours

(Maggs, 2001)

excellent n.d. no Topical treatment for

ocular FHV. Difficult

to source,

pharmacists can

formulate a 0.1%

ophthalmic solution.

Toxic if given

systemically

3


Ganciclovir Nucleoside

analogue

Topical excellent n.d. n.d. Topical treatment

for ocular FHV.

Good in vitro

activity (Maggs

and Clarke,

2004; van der

Meulen et al.,

2006)

3

Aciclovir Nucleoside

analogue

Topical and oral Poor

(high

doses

may be

needed

to

overc

ome

viral

resistanc

e)

some yes Least in vitro effect of

all herpes antivirals

(van der Meulen et

al., 2006; Williams et

al., 2004), moderate

in vivo effect

(Williams et al.,

2005). Synergy in

combination with

human IFN−α

(Weiss, 1989). Toxic

systematically

(Maggs,

2001; Maggs, 2010)

3

Systemic treatmentsFamciclovir N

ucleoside

analogue

(prodrug)

Oral, 90 mg/kg tid for

21 days

Yes (for

penciclovir,

as

famciclovir is

a prodrug

of

penciclovir)

yes yes Tested in conventional

and SPF cats

experimental

challenge, against

primary infection (Malik

et al., 2009; Thomasy

et al., 2011)

3

Feline IFN-ω Interferon Systemic

1 MU/kg SC sid or eod

Oral

50,000 – 100,000

units daily

Topical; dilute 10MU

vial in 19ml 0.9% NaCl

and use as eye drops:

2 drops in each eye 5

times a day for 10 days

(Jongh,

2004)

yes n.d. yes Safe and licensed for

use in cats.

A combined topical

and oral pre-treatment

before experimental

FHV infection was not

beneficial (Haid et al.,

2007)

Used along with L-

lysine in chronic

infections

4


Human IFN-

α

Interferon SC high dose

PO low dose

5-35 units daily

yes

yes

yes

yes

yes

yes

Less bioactive than

feline interferon.

5-35 units daily

reduces clinical signs

but not FHV shedding.

Used along with l-

lysine in chronic

infections

3

n.d. = not determined; eod = every other day; sid = once daily; bid = twice

daily; tid = three times daily.

The drugs listed may not be readily available or licensed for cats.

The amino acid l-lysine has been proposed for systemic treatment, to be

administered as a bolus, separate from food. No side effects have been published,

but reports on efficacy are conflicting (Maggs, 2001, 2010; Stiles et al., 2002;

Maggs et al., 2003, 2007; Rees and Lubinski, 2008; Drazenovich et al., 2009;

Gould, 2011). Cave et al. (2014) investigated the effects of physiologic

concentrations of l-lysine on the in vitro replication of FHV at L-arginine levels

sufficient to maintain cell growth. FHV was not inhibited at any l-lysine

concentration studied. The in vivo efficacy of the measure on primary and recurrent

FHV infection is unknown.

Other drugs have been proposed for the treatment of FHV ocular

infections, including bromovinyldeoxyuridine, HPMA, ribavirin, valacyclovir,

vidarabine, foscarnet and lactoferrin. However, the efficacy of these drugs

has not been proven.

General recommendations on vaccine type and vaccination protocol

This infection is common and may induce severe, even life-threatening

disease. ABCD therefore recommends that all cats should be vaccinated

against FHV. Vaccines provide protection through both an antibody

response and cellular immunity. Vaccination provides protection against

clinical signs and reduces viral shedding within one week after


administration (Jas et al., 2009), but – like in other respiratory tract

infections – it does not provide full protection; about 90% reduction in

clinical scores has been achieved following experimental challenge soon

after vaccination (Gaskell et al., 2007). In addition it can reduce field virus

excretion (Gaskell et al., 2007). Even less protection is expected under

particular circumstances like extreme challenge doses or

immunosuppression. Field strain variation does not play a role in protection

provided by vaccination.

Most current FHV vaccines are combined with FCV, either as bivalent

products (only in some countries) or with additional antigens. Both modified

live and inactivated parenteral vaccines are available. Subunit FHV

vaccines and modified intranasal vaccines have been or still are available

elsewhere, but no longer in Europe.

For routine vaccination, there is no reason to prefer any FHV vaccine

above another, since all are based on a single serotype. Modified live

vaccines might retain some pathogenic potential and may rarely induce

disease, e.g. when accidentally aerosolised or spilt on the skin and taken

up during grooming.

The value of serological tests in predicting protection is controversial.

Methodological issues can complicate comparison of titres (particularly

when obtained from different laboratories), and they are no good

predictors of protection. Also, cats without any evidence of seroconversion

have been found protected (Lappin et al., 2002; Mouzin et al., 2004).

Vaccinated cats usually develop an anamnestic response upon field

infection.

Primary vaccination course

Maternal antibodies interfere with the response to vaccination until 8 weeks of age

on average (Poulet, 2007); the primary course of vaccination is therefore usually

started at around nine weeks of age, although some products are licensed for

earlier use. Kittens should receive a second vaccination two to four weeks later,

with the second given around twelve weeks of age. This protocol has been


developed to ensure optimal protection. For longer intervals, no information is

available.

In contrast to vaccines against other infectious agents, where a single vaccination

is acceptable for adult cats of unknown or uncertain vaccination status, in the case

of FHV two vaccinations at an interval of two to four weeks are recommended,

irrespective of the vaccine type.

Booster vaccinations

ABCD recommends that boosters should be given at annual intervals to protect

individual cats against field infections. In low-risk situations (e.g. indoor-only cats

without contact to other cats), three-yearly intervals are recommended. An informed

decision should be taken on the basis of a risk-benefit analysis, but annual boosters

are particularly important in high risk situations, e.g. for boarding and breeding

catteries.

Experimental studies and serological surveys in the field have clearly shown that

immunity against FHV lasts longer than one year (Lappin et al., 2002, Mouzin et

al., 2004; EBM grade II). However, there is a significant proportion of cats for

which this might not be true. While most cats in the field either have antibody

against FCV and FPV, or show an anamnestic response after the booster, only

around 30% have titres against FHV, and around 20% fail to react to booster

vaccinations (Lappin et al., 2002; Mouzin et al., 2004). In experimental vaccine

efficacy studies, protection clearly decreases with time.

If booster vaccinations have lapsed, a single injection is adequate if the interval

since the last vaccination is less than three years; if it is more than three years,

two injections three weeks apart should be applied.

Boosters using FHV vaccines produced by another manufacturer are acceptable.

Cats that have recovered from disease caused by FHV may not enjoy lifelong

protection against further episodes. Furthermore, in most clinical cases, the

causative agent will not have been identified and the cat may contract infection

with other respiratory pathogens. To be on the safe side, vaccination of

recovered cats is generally recommended.


Disease control in specific situations

Multi-cat households

FHV infection is common in multi-cat households. Depending on the management,

ABCD recommendations will refer either to shelters or to breeding catteries.

Shelters

FHV infections can pose a problem in cat shelters. Management to prevent and

limit the spread of infection is as important as vaccination. In shelters where

incoming cats are mixed with resident ones, high infection rates are frequent. To

control this situation, newcomers should be quarantined for the first three weeks,

and kept individually – unless known to be from the same household. Shelter

design and management measures should be aimed at avoiding cross infections.

New cats should be vaccinated as soon as possible when they are healthy and no

contraindications to vaccination have been found. If there is a particularly high

risk, e.g. past or recent FHV infections, modified live vaccines are used, as these

provide earlier protection. In an acute respiratory disease outbreak, identification

of the agent involved – with differentiation between FHV and FCV – can be useful

in deciding on the appropriate preventive measures.

Breeding catteries

FHV infections can be a major problem in breeding catteries, where they most

often appear in young kittens before weaning - typically around 4 to 8 weeks of

age, when maternally derived immunity wanes. The source of infection is often the

queen, who is the virus carrier and whose latent infection has been reactivated in

the course of kittening and lactation.

Infection in such young kittens is often severe, involving the entire litter. Mortality

can be important, and some kittens that have recovered from the acute disease

are left with complications, notably chronic rhinitis. Vaccination of the queen is no

option since it will not prevent her from becoming a carrier. However, if the queen

has a good antibody titre, the kittens will benefit from high levels of MDA

transferred through the colostrum, which provide protection against disease for the


first weeks of life.

Booster vaccinations of the queen may therefore be indicated, which should ideally

take place prior to mating. Exceptionally, vaccination during pregnancy may be

considered (if this measure had been overlooked), but vaccines are not licensed

for use in pregnant cats, and in this situation, an inactivated product is preferable.

Queens should kitten in isolation, and litters should neither mix nor have contacts

with other cats until they have been fully vaccinated. Early vaccination should be

considered for litters from queens that had infected litters previously. The earliest

age for which FHV vaccines are licensed is 6 weeks, but kittens may become

susceptible to infection earlier than this as MDA wanes. Vaccination from around 4

weeks of age may be considered, to be repeated every 2 weeks until the primary

vaccination course is given as usual.

Early weaning into isolation from around 4 weeks of age is an alternative

approach to protecting kittens from maternal infection. There are no reliable tests

that will identify carrier queens and predict which may infect their kittens.

Vaccination of immunocompromised cats

Vaccines will not establish immunity in animals with a compromised immune

function. Systemic disease, genetic and virus-induced immunodeficiency, poor

nutrition, concurrent administration of immunosuppressive drugs and severe,

prolonged stress all are compromising factors. Such patients should be protected

from exposure to infectious agents in the first place, but vaccination using an

inactivated product should be considered.

FIV positive cats

FIV-positive healthy cats should be protected against FHV, by confining them

indoors. If this is not possible, vaccination should be considered. Concerns have

been raised that vaccination may contribute to the progression of FIV disease, but

the benefit of protecting a potentially immunocompromised cat outweighs this

small risk. Also, other infections may contribute to FIV progression.

In FIV-positive cats with a history of clinical problems but in a stable medical

condition, vaccination should be considered to ensure that FHV protection is


maintained. In cats suffering from FIV-related disease, vaccination is generally

discouraged, as in any systemically ill cat.

FeLV-positive cats

The same considerations apply to FeLV-positive cats. Vaccination is contra-

indicated if there are clinical signs related to the FeLV infection. If the cat appears

healthy, vaccination should be considered to maintain protection, if prevention of

exposure to FHV cannot be ensured.

Chronic disease

Booster vaccination should be continued in cats with stable chronic

conditions, such as hyperthyroidism and renal disease. Such cats are often

elderly and the consequences of infection can be particularly severe.

Cats receiving corticosteroids or other immunosuppressive drugs

Depending on the dosage and duration of treatment, corticosteroids may cause

suppression of immune responses. The effect of corticosteroids on vaccine

efficacy in cats is not known, nevertheless concurrent use of corticosteroids at the

time of vaccination should be avoided.

References

Binns SH, Dawson S, Speakman AJ, et al (2000). A study of feline upper

respiratory tract disease with reference to prevalence and risk factors for

infection with feline calicivirus and feline herpesvirus. J Feline Med Surg 2: 123-

133.

Brooks SE, Kaza V, Nakamura T, Trousdale MD (1994). Photoinactivation of

herpes simplex virus by rose bengal and fluorescein In vitro and in vivo studies.

Cornea 13: 43-50.

Burgener DC, Maes RK (1988). Glycoprotein-specific immune responses in cats

after exposure to feline herpesvirus-1. Am J Vet Res 49: 1673-1676.


Burgesser KM, Hotaling S, Schiebel A, Ashbaugh SE, Roberts SM, Collins JK

(1999). Comparison of PCR, virus isolation, and indirect fluorescent antibody,

staining in the detection of naturally occurring feline herpesvirus infections. J Vet

Diagn Invest 11: 122-126.

Cave NJ, Dennis K, Gopakumar G, Dunowska M (2014). Effects of physiologic

concentrations of l-lysine on in vitro replication of feline herpesvirus 1. Am J Vet

Res 75: 572-580.

Coutts AJ, Dawson S, Willoughby K, Gaskell RM (1994). Isolation of feline

respiratory viruses from clinically healthy cats at UK cat shows. Vet Rec 135: 555-

556.

Cullen CL, Wadowska DW, Singh A, Melekhovets Y (2005). Ultrastructural

findings in feline corneal sequestra. Vet Ophthalmol 8: 295-303.

Dawson DA, Carman J, Collins J, Hill S, Lappin MR (1998). Enzyme-linked

immunosorbent assay for detection of feline herpesvirus 1 IgG in serum, aqueous

humour, and cerebrospinal fluid. J Vet Diagn Invest 10: 315-319.

Dawson S, Willoughby K, Gaskell RM, Woog G, Chalmers WCK (2001). 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: 17-22.

Drazenovich TL, Fascetti AJ, Westermeyer HD, et al (2009). Effects of dietary

lysine supplementation on upper respiratory and ocular disease and detection of

infectious organisms in cats within an animal shelter. Am J Vet Res 70: 1391-1400.

Ellis TM (1981). Feline respiratory virus carriers in clinically healthy cats. Aust Vet J

57: 115-118.

Fontenelle JP, Powell CC, Veir JK, Radecki SV, Lappin MR (2008). Effect of topical

ophthalmic application of cidofovir on experimentally induced primary ocular feline

herpesvirus-1 infection in cats. Am J Vet Res 69: 289-293.

Gaskell R, Dawson S, Radford A. Feline respiratory disease (2006). Greene

CE, ed. Infectious diseases of the dog and cat. Missouri: WB Saunders, 145-

154.


Gaskell R, Dawson S, Radford A, Thiry E (2007). Feline herpesvirus. Vet Res 38:

337-354.

Gaskell RM, Povey RC (1977). Experimental induction of feline viral rhinotracheitis

(FVR) virus re-excretion in FVR-recovered cats. Vet Rec 100: 128-133.

Gaskell RM, Povey RC (1979). The dose response of cats to experimental

infection with feline viral rhinotracheitis virus. J Comp Pathol 89: 179-191.

Gaskell RM, Povey RC (1982). Transmission of feline viral rhinotracheitis. Vet Rec

111: 359-362.

Gould D (2011). Feline herpesvirus-1. Ocular manifestations, diagnosis and

treatment options. J Feline Med Surg 13: 333-346.

Haid C, Kaps S, Gönczi E, et al (2007). Pretreatment with feline interferon omega

and the course of subsequent infection with feline herpesvirus in cats. Vet

Ophthalmol 10: 278-284.

Hamano M, Maeda K, Mizukoshi F, Mochizuki M, Tohya Y, Akashi H, Kai K

(2004). Genetic rearrangements in the gC gene of the feline herpesvirus type 1.

Virus genes 28: 55-60.

Hara M, Fukuyama M, Suzuki Y, Kisikawa S, Ikeda T, Kiuchi A, Tabuchi K

(1996). Detection of feline herpes virus 1 DNA by the nested polymerase chain

reaction. Vet Microbiol 48: 345-352.

Hargis AM, Ginn PE (1999). Ulcerative facial and nasal dermatitis and stomatitis

in cats associated with feline herpesvirus-1. Vet Dermatol 10: 267-274.

Hartley C (2010). Aetiology of corneal ulcers. Assume FHV-1 unless proven

otherwise. J Feline Med Surg 12: 24-35.

Helps CR, Lait P, Damhuis A, et al (2005). Factors associated with upper

respiratory tract disease caused by feline herpesvirus, feline calicivirus,

Chlamydophila felis and Bordetella bronchiseptica in cats: experience from 218

European catteries. Vet Rec 159: 669-673.

Helps C, Reeves N, Egan K, Howard P, Harbour D (2003). Detection of


Chlamydophila felis and feline herpesvirus by multiplex real-time PCR analysis.

J Clin Microbiol 41: 2734-2736.

Henderson SM, Bradley K, Day MJ, et al (2004). Investigation of nasal

disease in the cat – a retrospective study of 77 cases. J Feline Med Surg 6:

245-257.

Jas D, Aeberle C, Lacombe V, Guiot AL, Poulet H (2009). Onset of immunity in

kittens after vaccination with a non-adjuvanted vaccine against feline

panleucopenia, feline calicivirus and feline herpesvirus. Vet J 182: 86–93.

Johnson LR, Foley JE, De Cockc HE, Clarke HE, Maggs DJ (2005). Assessment

of infectious organisms associated with chronic rhinosinusitis in cats. J Am Vet

Med Assoc 227: 579-585.

Johnson RP, Povey RC (1985). Vaccination against feline viral rhinotracheitis

in kittens with maternally derived feline viral rhinotracheitis antibodies. J Am

Vet Med Assoc 186:149-152.

Jongh O (2004). A cat with herpetic keratitis (primary stage of infection) treated

with feline omega interferon. In: Karine de Mari (ed.): Veterinary Interferon

Handbook. Carros: Virbac, 138-147.

Lappin MR, Andrews J, Simpson D, Jensen WA (2002). Use of serologic tests to

predict resistance to feline herpesvirus 1, feline calicivirus, and feline parvovirus

infection in cats. J Am Vet Med Assoc 220: 38-42.

Lappin MR, Sebring RW, Porter M, Radecki SJ, Veir J (2006). Effects of a single

dose of an intranasal feline herpesvirus 1, calicivirus, and panleukopenia vaccine

on clinical signs and virus shedding after challenge with virulent feline

herpesvirus 1. J Feline Med Surg 8: 158-163.

Maggs DJ (2001). Update on the diagnosis and management of feline

herpesvirus-1 infection. In: August JR (ed.): Consultations in Feline Internal

Medicine Volume 4, Philadelphia: WB Saunders Company: 51-61.

Maggs DJ (2005). Update on pathogenesis, diagnosis, and treatment of feline

herpesvirus type 1. Clin Tech Small Anim Pract 20: 94-101.


Maggs DJ (2010). Antiviral therapy for feline herpesvirus infections. Vet Clin North

Am Small Anim Pract 40: 1055-1062.

Maggs DJ, Clarke HE (2004). In vitro efficacy of ganciclovir, cidofovir, penciclovir,

foscarnet, idoxuridine, and acyclovir against feline herpesvirus type-1. Am J Vet

Res 65: 399-403.

Maggs DJ, Clarke HE (2005). Relative sensitivity of polymerase chain reaction

assays used for detection of feline herpesvirus type 1 DNA in clinical samples and

commercial vaccines. Am J Vet Res 66: 1550-1555.

Maggs DJ, Lappin MR, Nasisse MP (1999a). Detection of feline herpesvirus-specific

antibodies and DNA in aqueous humor from cats with and without uveitis. Am J Vet

Res 60: 932-936.

Maggs DJ, Lappin MR, Reif JS, et al (1999b). Evaluation of serologic and viral

detection methods for diagnosing feline herpesvirus-1 infection in cats with acute

respiratory tract or chronic ocular disease. J Am Vet Med Assoc 214: 502-507.

Maggs DJ, Nasisse MP, Kass PH (2003). Efficacy of oral supplementation

with L-lysine in cats latently infected with feline herpesvirus. Am J Vet Res 64:

37-42.

Maggs DJ, Sykes JE, Clarke HE, et al (2007). Effects of dietary lysine

supplementation in cats with enzootic upper respiratory disease. J Feline Med

Surg 9: 97-108.

Malik R, Lessels NS Meek M, et al (2009). Treatment of feline herpesvirus-1

associated disease in cats with famciclovir and related drugs. J Feline Med Surg

11: 40-48.

Marsilio F, Di Martino B, Aguzzi I, Meridiani I (2004). Duplex polymerase chain

reaction assay to screen for feline herpesvirus-1 and Chlamydophila spp. in

mucosal swabs from cats. Vet Res Commun 28: 295-298.

Mouzin DE, Lorenzen MJ, Haworth JD, King VL (2004). Duration of serologic

response to three viral antigens in cats. J Am Vet Med Assoc 224: 61-66.

Nasisse MP, Glover TL, Moore CP, Weigler BJ (1998). Detection of feline


herpesvirus 1 DNA in corneas of cats with eosinophilic keratitis or corneal

sequestration. Am J Vet Res 59: 856-858.

Nasisse MP, Guy JS, Davidson MG, Sussman WA, Fairley NM (1989).

Experimental ocular herpesvirus infection in the cat Sites of virus replication,

clinical features and effects of corticosteroid administration. Invest

Ophthalmol Vis Sci 30: 1758-1768.

Nasisse MP, Guy JS, Stevens JB, English RV, Davidson MG (1993). Clinical and

laboratory findings in chronic conjunctivitis in cats: 91 cases (1983-1991). J Am Vet

Med Assoc 203: 834-837.

Nasisse MP, Weigler BJ (1997). The diagnosis of ocular herpes virus infection. Vet

Comp Ophthalmol 7: 44-51.

Pedersen NC (1987). Feline herpesvirus type 1 (feline rhinotracheitis virus). In:

Appel MJ (ed.): Virus infections of carnivores. Amsterdam: Elsevier science

publishers: 227-237.

Pedersen NC, Satop R, Foley JE, Poland AM (2004). Common virus infections in

cats, before and after being placed in shelters, with emphasis on Feline enteric

coronavirus. J Feline Med Surg 6: 83-88.

Poulet H (2007). Alternative early life vaccination programs for companion animals.

J Comp Path 137: S67-S71.

Rees TM, Lubinski JL (2008). Oral supplementation with L-lysine did not prevent

upper respiratory infection in a shelter population of cats. J Feline Med Surg 10:

510-513.

Reubel GH, Ramos RA, Hickman MA, Rimstad E, Hoffmann DE, Pedersen NC

(1993). Detection of active and latent infections using the polymerase chain

reaction. Arch Virol 132: 409-420.

Slater Y, York C (1976). Comparative studies on parenteral and intranasal

inoculation of an attenuated feline herpes virus. Dev Biol Stand 33: 410-

416.

Spatz SJ, Rota PA, Maes RK (1994). Identification of the feline herpesvirus type


1 (FHV-1) genes encoding glycoproteins G, D, I and E: expression of FHV-1

glycoprotein D in vaccinia and raccoon poxviruses. J Gen Virol 75: 1235-1244.

Stiles J, McDermott M, Bigsby D, et al (1997a). Use of nested polymerase chain

reaction to identify feline herpesvirus in ocular tissue from clinically normal cats

and cats with corneal sequestra or conjunctivitis. Am J Vet Res 58: 338-342.

Stiles J, McDermott M, Willis M, Roberts W, Green C (1997b). Comparison of

nested polymerase chain reaction, virus isolation, and fluorescent antibody

testing for identifying feline herpesvirus in cats with conjunctivitis. Am J Vet Res

58: 804-847.

Stiles J, Townsend WM, Rogers QR, Krohne SG (2002). Effect of oral

administration of L-lysine on conjunctivitis caused by feline herpesvirus in cats.

Am J Vet Res 63: 99–103.

Storey ES, Gerding PA, Scherba G, Schaeffer DJ (2002). Survival of equine

herpesvirus-4, feline herpesvirus-1, and feline calicivirus in multidose ophthalmic

solutions. Vet Ophthalmol 5: 263-267.

Sykes JE, Allen JL, Studdert VP, Browning GF (2001). Detection of feline

calicivirus, feline herpesvirus 1 and Chlamydia psittaci mucosal swabs by

multiplex RT-PCR/PCR. Vet Microbiol 81: 95-108.

Thiry E (2006). Feline Herpesvirus. In Clinical virology of the dog and cat (Collection

Clinical Virology). Éditions du Point Vétérinaire, Maisons-Alfort (France): 91-97.

Thomasy SM, Lim CC, Reilly CM, Kass PH, Lappin MR, Maggs DG (2011).

Evaluation of orally administered famciclovir in cats experimentally infected with

feline herpesvirus type-1. Am J Vet Res 72: 85-95.

Van der Meulen K, Garre B, Croubels S, Nauwynck H (2006). In vitro comparison

of antiviral drugs against feline herpesvirus 1. BMC Vet Res 26: 13.

Vögtlin A, Fraefel C, Albini S, et al (2002). Quantification of feline herpesvirus 1

DNA in ocular fluid samples of clinically diseased cats by real-time TaqMan

PCR. J Clin Microbiol 40: 519-523.

Wardley RC, Rouse BT, Babiuk LA (1976). Observations on recovery


mechanisms from feline viral rhinotracheitis. Can J Comp Med 40: 257-264.

Weigler BJ, Babineau A, Sherry B, Nasisse MP (1997a). High sensitivity

polymerase chain reaction assay for active and latent feline herpesvirus-1

infections in domestic cats. Vet Rec 140: 335-338.

Weigler BJ, Guy JS, Nasisse MP, Hancock SI, Sherry B (1997b). Effect of a live

attenuated intranasal vaccine on latency and shedding of feline herpesvirus 1 in

domestic cats. Arch Virol 142: 2389-2400.

Weiss RC (1989). Synergistic antiviral activities of acyclovir and recombinant human

leukocyte (alpha) interferon on feline herpesvirus replication. Am J Vet Res 50:

1672-1677.

Westermeyer HD, Thomasy SM, Kado-Fong H, Maggs DJ (2009). Assessment of

viremia associated with experimental primary feline herpesvirus infection or

presumed herpetic recrudescence in cats. Am J Vet Res 70: 99-104.

Williams DL, Fitzmaurice T, Lay L, Forster K, Hefford J, Budge C, Blackmore K,

Robinson JC, Field HF (2004). Efficacy of antiviral agents in feline herpetic

keratitis: results of an in vitro study. Curr Eye Res 29: 215-218.

Williams DL, Robinson JC, Lay E, Field H (2005). Efficacy of topical aciclovir for

the treatment of feline herpetic keratitis: results of a prospective clinical trial and

data from in vitro investigations. Vet Rec 157: 254-257.

For further reading:Cave TA, Thompson H, Reid SWJ, Hodgson DR, Addie DD (2002). Kitten

mortality in the United Kingdom, a retrospective analysis of 274 histopathological

examinations (1986-2000). Vet Rec 151: 497-501.

Lommer MJ, Verstraete FJM (2003). Concurrent oral shedding of feline calicivirus

and feline herpesvirus 1 in cats with chronic gingivostomatitis. Oral Microbiol

immunol 18: 131-134.

Radford AD, Gaskell RM, Dawson S (2004). Feline Viral Upper Respiratory Disease.

In Textbook of Respiratory Disease in Dogs and Cats, LG King (ed.), WB Saunders,

Missouri; 271-278.


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