Although canine herpesvirus (CHV) (also referred to as canine herpesvirus 1, canid
herpesvirus 1, neonatal herpes, genital herpes, ocular herpes, and CHV-1) infections
and related diseases have been recognized since the early 1960s,1, 2, 3, 4, 5 there
has been a resurgence of interest in the various clinical manifestations of the virus,
which makes this review very timely.6, 7, 8, 9, 10, 11 The various forms of CHV-associated
infections are listed in Table 1. In some cases these infections were directly related
to clinical symptoms, such as acute neonatal viremia resulting in puppy mortality;
systemic viremia in naive pregnant females resulting in fetal death, abortion, and
mummification; and ocular-respiratory disease in dogs of various age ranges.
Clinical features of canine herpesvirus infection and disease
Age Groups at Risk
1. Mucosal form (respiratory/vaginal)
Older puppies (>3 weeks) and adults
Mild, often inapparent infection, active shedding, with establishment of latency
2. Latent infection
Older puppies, adults, and survivors of neonatal and mucosal forms
Lifelong infection, may show recrudescence at pregnancy and stress
3. Acute neonatal viremia
Puppies from birth to 3 weeks
Fatal systemic disease, active shedding, poor prognosis
4. Systemic infection of naïve pregnant females
Fetal death, abortion, mummification, source of virus for acute neonatal viremia
5. Ocular form
Older puppies (> 3 wks) and adults
Mild conjunctivitis to severe ocular disease, with active shedding
Data from Anvik JO. Clinical considerations of canine herpesvirus infection. Vet Med
What has changed within the past decade has been the ability to detect the virus in
its subclinical state, which allows for a much clearer understanding of the importance
of 2 subpopulations of dogs: carrier-shedder adult dogs, and CHV–latently infected
dogs in the animal populations with which we work.13, 14, 15, 16, 17 The increased
sensitivity of both antibody-based serology assays and nucleic acid–based polymerase
chain reaction (PCR) assays have increased our level of clinical inquiry regarding
CHV, as well as the other canine infectious microorganisms.18, 19, 20, 21, 22 In addition
to recognizing CHV adult carriers in the general population, this new momentum has
allowed for clinicians to screen dogs that are undergoing immunosuppressive regimens
of therapy for various dermatologic conditions, as well as dogs being treated for
various cancers. This review will provide a brief overview of the reproductive aspects
of CHV disease and will then bring together the current literature, documenting the
involvement of CHV in adult dog respiratory and ocular diseases.
Contemporary Clinical Observations
Consistent with the other alpha herpesviruses, CHV has a predilection for pregnant
dogs and neonatal puppies.23, 24, 25, 26 Early reports focused on the effects of CHV
on various reproductive parameters in the dog, in part due to the severity of the
clinical symptoms and the profound pathologic effects. In the review by Anvik,
acute neonatal viremia and systemic infection of naïve pregnant females were regarded
as 2 of the most important disease outcomes of CHV infection. The emphasis at that
time was on the recognition of clinical symptoms for a rapid diagnosis. Since there
are no commercial vaccines currently available for the prevention of CHV-induced disease,
it has become paramount to understand the clinical features of CHV infections (see
Table 1) and to incorporate this knowledge with sound management practices to minimize
the effects on reproductive efficiency and puppy survival.
As was mentioned previously, this has been the primary focus of the earlier literature
on CHV infections. Infection may occur during pregnancy or may be acquired by puppies
during the first few weeks of life. The key feature during both of these phases is
that the pregnant female and puppies are immunologically naïve to CHV and therefore
highly susceptible to disease. Puppies may acquire the infection in utero, from passage
through the birth canal, from contact with oronasal secretions of the dam, or contact
shedders. Humans may serve as fomites of the virus if attending to an adult carrier-shedder
dog, and then proceeding to a nursery setting without proper disinfection. Naïve neonatal
puppies, younger than 1 week, are at highest risk of fatal systemic disease, while
naïve dogs older than 3 weeks are relatively resistant to disease but can still become
infected.27, 28, 29 Virus infection in naïve older dogs is generally acquired via
aerosol, so that replication occurs in the nasopharynx tonsils and retropharyngeal
and bronchial lymph nodes.2, 30, 31, 32 This respiratory site will become an important
aspect of the ecology of the virus when both respiratory and ocular clinical outcomes
are covered in subsequent sections.
Although neonatal infections are regarded as the most common, in utero infection with
CHV may occur. Infertility and abortion of stillborn or of weak pups has been reported.
While the mortality rate usually approaches 100% for the fetal puppy, there may be
no further clinical manifestations reported in the dam.1, 5, 26
Passive immunity acquired from the dam appears to be of primary biological importance
in the survival of infected pups.12, 27, 33, 34, 35 Puppies that are nursing from
CHV-seronegative dams usually develop the fatal multisystemic disease, while puppies
that suckle from CHV-seropositive dams remain asymptomatic but still become infected.
The CHV is usually recovered from the oropharyngeal region in these disease-resistant
pups. It is generally accepted that maternal antibody and/or immune lymphocytes acquired
through the milk explain why naturally infected dams that have a diseased litter will
usually give birth to normal litters on subsequent pregnancies.
Since CHV is one of the few canine viral infections that can proceed to fatal disease
and there is no commercial vaccine routinely available, it has become necessary for
infection management to prevent reproductive disease. The literature has focused on
3 aspects of the virus and its relationship with host immunity and its carrier-spread
dynamics within a population of susceptible dogs.
Infection management—understanding the risk factors
The risk factors associated with CHV infection and reproductive disease has been intensively
studied over the past 5 years.36, 37 The studies have used various diagnostic assays
including serology, virus isolation, and polymerase chain reaction (PCR). These studies
have provided valuable information on controlling CHV-associated reproductive diseases
(ie, infertility, abortion, stillbirths, and neonatal mortality). Table 2
lists the 12 risk factors that were studied and whether there was an association with
reproductive disease. Of the 12 factors, 8 were identified as having a positive correlation
with disease: breeding kennel, age, mating experience, cycle (stage), concurrent kennel
cough, kennel size, breeding management, and hygiene.
Risk factors studied to determine the association between CHV infection and reproductive
diseases in dogs
77 kennels sampled
Male (n = 137); female (n =4 09)
Attended or not
41 different breeds
14 different age ranges
Males mated or not
Five different stages
Number of litters
Zero to >1
History of respiratory disease
Ranged from <6 to >20 dogs
Use of nonresident males
Ranged from very good to insufficient
Data from Evermann JF. Canine herpesvirus infection: Update on risk factors and control
measures. Vet Forum 2005;69:32–7; and Ronsse V, Verstegen J, Onclin K, et al. Risk
factors and reproductive disorders associated with canine herpesvirus-1 (CHV-1). Theriogenology
The underlying risks in the aforementioned factors are CHV infection and an immune
susceptible dog. This has led to strategies to naturally immunize (via contact with
adult dogs) susceptible female dogs prebreeding, to screen female dogs for CHV infection
(by serology and/or PCR) prior to breeding, and to use a defined quarantine period
for pregnant dogs with an unknown CHV infection status. An age-risk, immunologically
naïve-risk strategy has been used by clinicians and clients to focus on the most susceptible
time periods for disease. This time encompasses the pregnant female during the last
3 weeks prior to whelping, and her puppies up to 3 weeks post whelping.12, 27, 33
This understanding has constituted the rationale for the “6-week danger period.”12,
The primary contributing risk factors that allow for CHV infection and disease are
kennel size, hygiene, and kennel cough. All 3 of these are important in the spread
and retention of CHV in high-risk dog populations. While the controversy over CHV
being a significant contributor to the kennel cough syndrome has been an ongoing debate
(see subsequent section on respiratory–ocular infections), it should be noted that
CHV was initially reported as a respiratory pathogen as early as it was a reproductive
The data from Ronsse and coworkers
support the contention that CHV is primarily maintained and spread among dogs in a
multidog environment as a respiratory infection.
The disease outcomes of CHV infections are age dependent. In naive puppies that are
less than 1 month of age, natural and experimental infection with CHV may be highly
fatal. Natural exposure of pups occurs by ingestion or inhalation of virus containing
material. The primary replication sites are nasal mucosa, pharynx, and tonsil. Systemic
spread of the virus is enhanced by a cell-associated viremia.29, 30, 31, 32 The pathology
induced by CHV in the lungs of newborn pups is depicted in Figs. 1
Dog, puppy, canine herpesvirus 1 infection. The lung is diffusely non-collapsed and
has numerous small coalescing pale foci suggestive of a necrotizing interstitial pneumonia.
(Courtesy of Dr David Driemeier, Universidade Federal do Rio Grande do Sul, Porto
Alegre, RS, Brazil.)
(A) Dog, puppy (2 weeks of age), canine herpesvirus 1 infection. The pulmonary parenchyma
is focally effaced by fibrin exudate and necrotic cell debris (*). Similar exudate
also fills part of the bronchiolar lumen (B). The alveolar septa in the remaining
lung are mildly expanded by inflammatory cell infiltrate (fibrinonecrotizing bronchointerstitial
pneumonia) (hematoxylin-eosin, original magnification ×20). (B) Dog, puppy (2 weeks
of age), canine herpesvirus 1 infection. High magnification of the previous figure.
An epithelial cell contains a round, eosinophilic, intranuclear inclusion body surrounded
by a clear halo and marginated chromatin within an area of lymphohistiocytic inflammation
of the pulmonary parenchyma (hematoxylin-eosin, original magnification ×60).
(Courtesy of Dr Ingeborg Langohr, Michigan State University, East Lansing, MI.)
Experimental infection of older dogs (3 months or older) with CHV has resulted in
a mild rhinitis and pharyngitis. Symptoms of tracheobronchitis were produced following
experimental inoculation with CHV isolated from naturally infected dogs.38, 39 Experimental
infection of 5- to 12-week-old pups induced mild rhinitis and pharyngitis and virus
replication was demonstrated in the upper respiratory tract. Although CHV has been
isolated from dogs with upper respiratory disease, reproduction of “kennel cough”
has only been rarely reported. Thompson and coworkers
reported that aerosol exposure of 12-week-old dogs caused a necrotizing rhinitis,
broncheointerstitial pneumonia, and multifocal alveolar necrosis. More severe disease
can occur when CHV infects dogs that are immunosuppressed.
A case of generalized CHV infection in a 9-year-old dog with a normal immune system
was documented recently (Gadsden BJ, Langohr IM, Maes R. Fatal herpesviral infection
in an adult dog. Submitted for publication, 2011). The most severe lesions were seen
in the liver. The histologic lesions observed in the lung of this dog are presented
in Fig. 3.
(A) Dog, adult dog (9 years of age), canine herpesvirus 1 infection. The pulmonary
architecture is focally mildly disrupted by fibrin, cell debris, and hemorrhage (*).
Vessels are acutely congested and alveoli are flooded with macrophages and proteinaceous
material indicative of diffuse pulmonary edema (hematoxylin-eosin, original magnification
×20). (Courtesy of Dr Ingeborg Langohr, Michigan State University, East Lansing, MI.)
(B) Liver; dog. Canid herpesviral 1 protein is detected within areas of hepatic necrosis
(immunohistochemistry). (Courtesy of Dr Matti Kiupel, Michigan State University, East
Lansing, MI.) (C) Liver; dog. Canid herpesviral 1 nucleic acid is present in the areas
of hepatic necrosis. In situ hybridization.
(Courtesy of Dr Matti Kiupel, Michigan State University, East Lansing, MI.)
Infection rates, based on serologic studies, are high enough to explain entry of CHV
into multidog environments, either as an active infection or as the result of reactivation
of latent virus in environments associated with natural, or pharmacologically induced
immunosuppression. In Belgium the seroprevalence in adult dogs was found to be 45.8%.
Rijsewijk and colleagues
reported a seroprevalence of 39% in the Netherlands. Reading and Field,
using an antibody detection ELISA, found a seroprevalence of 88% in the United Kingdom.
In Japan, the seroprevalence was recently reported to be 21.7%.
Since CHV is regarded as a weak immunogen, these antibody-based surveys are probably
an underrepresentation of the true infection rate in the dog populations.
Canine infectious respiratory disease (CIRD) is most commonly seen in rescue centers,
boarding kennels, and veterinary hospitals. Most of the affected dogs have a dry cough
of limited duration. In complicated cases, bronchopneumonia is seen and can be fatal.
Multiple infectious agents can play a role in the induction of CIRD. Canine parainfluenza
virus and Bordetella bronchiseptica are frequently involved. Canine distemper and
canine adenovirus type 2 (CAV-2) have been associated with CIRD but are not routinely
detected due in part to effective vaccines, and the population immunity is fairly
high. Canine influenza, canine respiratory coronavirus, and, most recently, canine
pneumovirus, are emerging components of CIRD, which have added to the complexity of
this disease syndrome.18, 19, 40
Although CHV infections have been documented in multidog environments, its etiologic
role in CIRD is still being assessed. During a 2-year longitudinal study of viruses
associated with CIRD at a rescue center in the United Kingdom, CHV was found in 12.8%
of the tracheal samples examined and in 9.6% of the lung samples. Infections with
CHV were seen 3 to 4 weeks after entry and were associated with more severe respiratory
The delay in detection of the virus by PCR was corroborated by the serologic data,
which also indicated that CHV infections occurred at a later time point. A possible
explanation offered for its detection in more severe cases was the possibility that
latent CHV could have been reactivated as a result of the stress induced by a primary
CIRD episode that was triggered by other viral or bacterial agents. The virus source
was not determined. The authors speculated that genetically different CHV strains
would have been detected if the source of virus was the result of reactivation of
latent virus from different dogs. It has been reported, however, that CHV strains
show very low sequence variability.
Erles and Brownlie
monitored dogs in 2 training centers in the United Kingdom for 1 year. All dogs were
vaccinated against CAV-2, CPV-2, and Leptospira interrogans. Tonsillar swabs and serum
samples were collected at entry and every 3 months thereafter. Blood samples were
collected at entry and every 4 weeks thereafter. Most CIRD cases were observed in
autumn and winter. Most dogs were healthy at arrival and were in the kennel for at
least 2 weeks before developing clinical signs. Seroconversion to CHV was detected
throughout the year. The most logical explanation for the seroconversion pattern would
be continuous introduction in the kennel by acutely infected dogs or reactivation
of latent virus in the resident population. The authors concluded that while CHV contributed
to the CIRD, it was not an obligate pathogen in that environment, since some asymptomatic
dogs also seroconverted.
Kawakami and colleagues
described an outbreak of infectious tracheobronchitis in Japan accompanied by death
in adult dogs. The only pathogen identified during the outbreak was CHV. Molecular
testing led to the conclusion that a single strain was involved, with virulence characteristics
that were only slightly higher than those of previously tested CHV strains. As was
the case in the study reported by Erles and colleagues,
it was not clear whether the virus was introduced into the center in the form of acute
infections or was the result of reactivation of latent infections in the resident
population. Regardless, the authors emphasized that there was sufficient amounts of
immunosuppression in shelter populations to allow for CHV to be a significant primary
pathogen in that environment.
Ocular manifestations of CHV infection may develop during both primary and recurrent
infection and are dependent upon host age and immune status. In fetal and neonatal
dogs with primary CHV infection, severe intraocular lesions are frequently present
concurrent with systemic viral disease. Subclinical or mild recurrent ocular surface
disease is typically observed in immunocompetent mature dogs. In immunosuppressed
mature dogs, ocular lesions associated with CHV infected are often more severe, persist
for a longer duration, and may be refractory to treatment.
Primary CHV infection in fetal and neonatal dogs
Primary CHV infection occurring after in utero or early neonatal CHV transmission
(ie, first 2 to 3 weeks of life) is associated with a cell-associated viremia. Hematogeneous
dissemination of virus results in CHV infection of intraocular tissues with severe
clinical ocular manifestations. Ocular disease is typically bilateral and becomes
evident within a short period after the development of systemic disease in many, but
not all, dogs.1, 3 Panuveitis, retinitis, and optic neuritis with extensive monocular
and neutrophilic infiltrates, edema, hemorrhage, and necrosis are observed histopathologically
within the iris, ciliary body, choroid, retina, and optic nerve.
Intranuclear viral inclusions are frequently detected during the acute inflammatory
phase in uveal and retinal tissues. As the palpebral fissures do not open until 10
to 14 days postpartum in dogs, ocular changes may not be externally visible in young
animals. In dogs with open eyelids, most clinically detectable ocular lesions are
sequelae to panuveitis and include keratitis, corneal edema, aqueous flare, anterior
synechiae, cataracts, and chorioretinitis (Fig. 4).
Reduced vision or blindness may result from various combinations of the ocular lesions.
Canine herpesvirus disease in puppy (12 days old). Diffuse corneal edema, marked aqueous
flare, and a mature cataract are evident.
Following the acute inflammatory stage of infection, developmentally mature tissues
(eg, cornea, uvea) undergo varying degrees of necrosis, fibrosis, gliosis, and atrophy.
The canine retina is incompletely developed at birth and responds by a combination
of necrosis, disorganization, and reorganization. Retinal dysplasia, characterized
by formation of retinal folds with rosette-like structures, and retinal degeneration
are the final result. In dogs surviving neonatal CHV infection, blindness, cataracts,
optic nerve atrophy, retinal degeneration, and retinal dysplasia are frequent residual
Primary and recurrent ocular CHV infections in mature dogs
In contrast to fetal and neonatal dogs, ocular lesions associated with CHV infection
in mature dogs are typically restricted to the ocular surface with a variety of corneal,
conjunctival, and eyelid lesions.
In immunocompetent dogs these lesions are frequently mild and self-limiting; however,
they are a source of discomfort and their recurrent nature may be frustrating to clients.
Nonspecific clinical signs associated with CHV ocular infection in mature dogs include
blepharospasm, photophobia, and ocular discharge. Blepharospasm and ocular pain are
often disproportionally severe compared to that expected from the extent of ocular
lesions. Ocular discharge is initially restricted to epiphora, but becomes mucoid,
mucopurulent, or serosanguineous with progression of infection.7, 44
Primary and recurrent ocular CHV infection may be subclinical or associated with various
combinations of blepharitis, conjunctivitis, keratitis, and corneal ulceration.7,
44, 45, 46 In all published descriptions of naturally-acquired primary ocular CHV
infection, clinical lesions were bilateral; however, the severity and specific manifestations
of CHV infection were not always symmetrical between eyes of individual dogs. In most
cases, primary ocular CHV infection resolves spontaneously and without permanent ocular
lesions; however, recovered dogs are at risk for developing recrudescent ocular disease
associated with reactivation of latent CHV. Recrudescent CHV ocular disease may present
with either unilateral or bilateral lesions. Recurrent CHV ocular infection may occur
in dogs with no identifiable risk factors; however, an immunocompromise state is present
in most dogs.7, 44 Naturally acquired recurrent CHV ocular infection is reported in
dogs with a variety of immunomodulating systemic conditions and receiving a variety
of immunosuppressive therapeutics. Systemic conditions included diabetes mellitus,
immune-mediated thrombocytopenia, and lymphoma. Immunosuppressive therapeutics included
topical ocular corticosteroids, topical ocular cyclosporine, systemic corticosteroids,
and a variety of antineoplastic chemotherapeutics (eg, cyclophosphamide, doxorubicin,
vincristine). In many reported dogs, potentially immunosuppressive conditions were
concurrently present with the administration of multiple topical and systemic immunosuppressive
Blepharitis is occasionally present with ocular CHV and may appear as focal or generalized
eyelid erythema, edema, exudates, and crusting. Regions of alopecia may be present.
The blepharitis may represent self-trauma resulting from discomfort associated with
conjunctival or corneal disease, or active viral infection of eyelid cutaneous epithelium
as described for other dermal regions in dogs with CHV infection.
Conjunctivitis is the most frequently reported ocular lesion associated with both
primary and recurrent CHV infection44, 47 and can be presented with conjunctival hyperemia,
chemosis, and ocular discharge. Ulceration of the conjunctival epithelium may occur
and appears as flat, irregular, pale or pink regions on the conjunctival surface surrounded
by regions of hyperemia. Conjunctival ulcerations are readily detected with application
of sodium fluorescein, rose Bengal, or lissamine green stains. Although the clinical
features of CHV conjunctivitis are often indistinguishable from other etiologies,
conjunctival petechiae are frequently reported in dogs with CHV infection (Fig. 5).
9, 44, 47 Although not specific to CHV infection, this clinical finding is uncommon
with most other etiologies of conjunctivitis and should be considered suggestive of
Canine herpesvirus disease in adult dog (8 years old). Recurrent blepharoconjunctivitis
following administration of chemotherapy for lymphoma. Eyelid erythema, mucopurulent
ocular discharge, conjunctival hyperemia, chemosis, and conjunctival petechiae are
Ulcerative keratitis and nonulcerative keratitis are frequent lesions associated with
primary and recurrent ocular CHV infection.7, 8, 47 A variety of clinical manifestations
are observed in the cornea associated with CHV infection and these likely represent
a continuum along the progression of active corneal epithelial infection. Punctate
keratitis is the earliest detectable CHV corneal ulceration and appears clinically
as a fine stippling of epithelial loss. This subtle lesion is often clinically overlooked
when examination is performed without the aid of magnification, but application of
corneal vital stains (particularly rose Bengal or lissamine green) facilitate detection.
As punctate ulcerations progress, they form the classic alphaherpesvirus corneal lesion
of dendritic corneal ulcers. Dendritic corneal ulcerations are strongly suggestive
of CHV infection in the dog. These linear, branching ulcers stain brightly with sodium
fluorescein, rose Bengal, and lissamine green (Fig. 6).
7, 47 Prominent terminal end bulbs are a consistent feature of CHV dendritic ulcers
in the dog and can be used to differentiate CHV corneal lesions from other potential
causes of linear corneal ulcers that might appear clinically similar (eg, external
trauma, cilia abnormalities, entropion). Terminal end bulbs are club-shaped, rounded
ends to the CHV dendritic ulcer branches, and are not seen with other causes of linear
corneal ulcers. Coalescence of dendritic ulcerations may result in the formation of
geographic corneal ulcers.
These appear as larger, irregular-shaped areas of corneal epithelial loss. In dogs
with CHV ulcerative keratitis, corneal ulcers are commonly located in discrete groups
or linear arrangements on the corneal surface. Unless complicated by secondary bacterial
infection, CHV corneal ulcers remain superficial and corneal stromal loss is not appreciable.
Nonulcerative keratitis is a less frequent lesion reported with CHV ocular infection.
Clinically, nonulcerative keratitis appears as a circumferential ring of cornea stromal
neovascularization with epithelial and subepithelial leukocyte infiltrates in the
peripheral cornea. Nonulcerative keratitis may represent a resolution stage of active
corneal epithelial disease.
Canine herpesvirus disease in adult dog (10 years old). Dendritic corneal ulcerations
developed during topical ocular corticosteroid treatment. Fluorescein-stained linear,
branching, superficial corneal ulcerations with prominent terminal end bulbs are detected
in the central cornea.
The largest published case series of primary CHV ocular disease described an outbreak
of CHV infection a closed colony of young adult laboratory beagles.
In this group of 27 dogs, conjunctivitis was detected in 100% of dogs, ulcerative
keratitis in 26% of dogs, and nonulcerative keratitis in 19% of dogs. Corneal ulcerations
were further subclassified by clinical appearance as punctate (7% of dogs), dendritic
(19% of dogs), and geographic (4% of dogs). This report confirmed CHV-associated ocular
disease in group housed susceptible dogs, and provides an overview of the spectrum
and relative frequency of ocular lesions associated with primary ocular CHV infection
Under experimental conditions, acquisition of primary CHV infection by ocular surface
inoculation consistently produces self-limiting conjunctivitis in immunocompetent
mature dogs.29, 46 This route of infection likely occurs frequently under natural
conditions and has direct clinical relevance.
Viral inoculation by other anatomic routes, such as the genital tract, is associated
with inconsistent development of ocular disease.
Clinical signs were manifested in both eyes, even when viral inoculation was unilateral,
but the magnitude of conjunctivitis may not be symmetric between eyes. The clinical
severity of ocular lesions peak approximately 7 to 10 days after infection and lesions
slowly resolve over the following 2 weeks. Histopathologic findings in dogs with acute
experimental CHV conjunctivitis include conjunctival epithelial necrosis, subepithelial
lymphocyte and macrophage infiltration, and edema of the substantia propria.28, 29
Experimental induction of recurrent ocular CHV infection was demonstrated by administering
immunosuppressive dosages of systemic corticosteroids to latently infected dogs recovered
from primary CHV ocular infection.
Recrudescent CHV ocular disease was detected in 83% of immunosuppressed dogs in one
Bilateral conjunctivitis or linear corneal ulcers developed as early as 3 days after
initiating corticosteroid administration. The mean duration of detectable ocular disease
was 8.6 days and was shorter than the experimental primary ocular CHV infection in
the dogs. Cellular lesions observed by in vivo confocal microscopy in the dogs included
conjunctival leukocyte infiltrates, corneal leukocyte infiltrates, abnormal corneal
epithelial cell morphologies, and corneal Langerhans cell infiltrates. Subsequent
research determined topical ocular corticosteroid administration does not result in
recurrent CHV ocular disease in latently infected dogs under experimental conditions.
In this study, topical ophthalmic prednisolone acetate (1.0% suspension) was administered
4 times daily for 28 days to both eyes of dogs with experimentally induced latent
CHV infection. Viral shedding and recurrent CHV ocular disease were not detected;
however, crystalline corneal opacities developed in some dogs. These bilateral corneal
lesions appeared clinically as subepithelial and anterior stromal punctate, white,
refractile opacities within the central cornea. It was unclear if the crystalline
corneal opacities were a nonspecific result of corticosteroid administration or influenced
by prior CHV corneal disease.
In immunocompromised dogs, such as lymphoma who are receiving chemotherapy or dogs
with autoimmune systemic disorders receiving long-term immunosuppressive therapy,
relatively severe ocular lesions may develop during recurrent CHV infection.7, 9 These
lesions include severe ulcerative conjunctivitis and extensive corneal ulceration
that is refractory to treatment. Development of viremia, systemic CHV dissemination,
and visceral hemorrhagic necrosis, similar to what is typically observed in fetal
and neonatal dogs, has been reported in a mature dog with ocular CHV infection while
receiving chemotherapy for lymphoma.
In the reported dog, it was speculated that viremia and systemic CHV disease developed
secondary to localized ocular CHV reactivation with an insufficient immune response
to contain virus to the anatomic site of recurrent disease.
Recent evidence suggests CHV ocular diseases in mature dogs are clinically underappreciated.
A survey of dogs with idiopathic conjunctivitis determined CHV was the most common
viral etiology of conjunctivitis in mature, vaccinated dogs and was detected in ocular
samples from approximately 17% of study dogs.
Conjunctivitis is among the most common ocular diseases in dogs presented to veterinarians
and, if these results are extrapolated to the general canine population, it implies
CHV ocular diseases occur commonly.
To determine the sites of latency of CHV, Miyoshi and colleagues
experimentally inoculated adult seronegative dogs via the intranasal (n = 2), intranasal
and intravenous (n = 3), or intravaginal (n = 3) routes with a strain of CHV. Although
clinical signs were not observed, infectious virus was isolated from swabs until 4
to 6 days postinoculation. Tissues were collected 2 to 4 months postinoculation and
examined for the presence of latent viral DNA. It was determined that the trigeminal
ganglion (TG) was an important latency site for CHV, regardless of the inoculation
route. Latency was detected also in lumbosacral ganglia of 2 of 3 dogs inoculated
intravaginally, 1 of 2 dogs inoculated intranasally, and 1 of 3 dogs inoculated both
intranasally and intravenously. Abortion and stillbirths could also be associated
with reactivation of latent CHV, but the mechanism by which this takes place has not
been investigated. Retropharyngeal lymph nodes were another important latency site,
since latency was detected in this tissue in 7 of 8 dogs. Conversely, all attempts
to demonstrate latency in peripheral blood lymphoid cells were negative.
In humans, herpesviruses have been detected in the inner ear and are considered to
play a role in vestibular dysfunction. Parzefall and colleagues
reported on the prevalence of canine herpesvirus DNA in the vestibular ganglia (VG)
and vestibular labyrinth (VL) of 52 dogs that were included in their study. CHV DNA
was detected in the VL of 17% of the dogs and in the VG of 19% of the dogs. Although
no attempt was made to differentiate between acute and latent infection, it is very
likely that the PCR was detecting latent virus. Interestingly, infection of the VG
or VL was not always associated with infection of TG. Since the VG, in contrast to
the trigeminal and geniculate ganglia, do not have direct connection with sensory
nerve endings on body surfaces, it remains most probable that there was primary infection
of the TG or geniculate ganglia, with subsequent spread to the VG.
Burr and colleagues
examined tissues from 12 adult dogs that had been euthanized for various reasons.
From each dog 12 tissues that have been associated with latency in other herpesvirus
infections were examined. Viral DNA was detected in the organs of 9 of the 12 dogs.
The tissues most commonly found to be positive were lumbosacral ganglia, tonsil, parotid
salivary gland, and liver. Based on the data, lumbosacral ganglia are an important
site of latency and potential source of reactivated virus for venereal infections
and infection of pups as they pass through the birth canal. Finding of latent virus
in tonsils and salivary glands points to the role of oronasal spread in the transmission
of CHV. It was noted that viral DNA was detected in the trigeminal ganglia extracts
of only 2 of the dogs. None of the 12 blood samples tested were found to be positive,
indicting a lack of detectable viremia. The authors commented that CHV is either totally
absent from peripheral blood or that the level of infection is limited to 1 genomic
copy per 2000 mononuclear cells. They also pointed out that basing the incidence of
CHV infection on serology only may lead to an underestimation of the true infection
The difficulty in detecting circulating CHV in a kennel situation is highlighted in
a study by Ronsse and colleagues.
Dogs in a breeding facility were followed for the duration of 1 reproductive cycle.
A number of dogs seroconverted (negative to positive) to CHV during this period. Conversely,
antibody-positive dogs became seronegative. The serologic data clearly indicate that
CHV was circulating in this kennel in the form of acute and/or reactivated form, primary
infections. However, despite the fact that samples were taken at regular intervals,
the results of PCR testing with a previously validated assay were uniformly negative
both on all nasal and vaginal swabs and buffy coat samples. A possible explanation
is that the shedding interval after reactivation is very short. Even during acute
infection, shedding of CHV is limited to 2 to 6 days.
Reactivation Following Corticosteroid Administration
Latent CHV has been reactivated by treatment with corticosteroids. Okuda and colleagues
treated dams with a history of CHV infection with 600 mg of prednisolone for 5 consecutive
days. Reactivation of latent CHV infection was confirmed in 4 of 5 dams. Infectious
CHV was recovered from nasal, oral, vaginal, and ocular secretions on the 5th to 21st
days after initiation of treatment and also from nasal mucosa and tonsil tissues.
These results indicate that latent CHV infections develop frequently and that the
latent virus may be reactivated, without clinical signs, in dogs with a history of
Ledbetter and colleagues
investigated whether systemic administration of an immunosuppressive regimen of corticosteroids
(3 mg/kg/day for 7 consecutive days) to experimental adult dogs would lead to reactivation
and recrudescence. Group1 dogs were latently infected and received corticosteroid
treatment. Group 2 dogs were latently infected and received a placebo. Group 3 dogs
were control dogs and received corticosteroid treatment. Bilateral ocular disease,
consisting of conjunctivitis and keratitis, was seen in 83% of the group 1 dogs between
days 3 and 18 of the experiment. Ocular shedding was detected in 50% of the group
1 dogs, and a 4-fold rise in antibody titer was detected in all dogs in group 1. None
of the dogs in the control groups showed ocular disease, shed virus, or seroconverted.
Corticosteroid-induced reactivation is likely the result of enhanced expression of
both viral and cellular genes. Corticosteroid also lead to host immune response suppression,
As discussed by the authors, the immunosuppression could be involved directly in the
reactivation event, or indirectly in facilitating the spread of reactivated virus
to peripheral tissues, leading to renewed replication at peripheral mucosal sites
and potential transmission to susceptible animals that are in contact with the animal
in which reactivation takes place.
Ledbetter and colleagues
also administered topical ocular prednisolone acetate or a placebo to mature dogs
experimentally inoculated with CHV via the ocular route and previously tested for
reactivatable latency by systemic administration of an immunosuppressive dose of corticosteroids.
The dogs were treated 4 times daily for a total of 28 days. The results of this study
showed that topical ocular prednisolone at the concentration and treatment regimen
used did not result in detectable reactivation of CHV latency, based on a combination
of recrudescent clinical signs, confocal microscopy findings, ocular infectious virus
shedding, real-time PCR findings, and serologic response. A potential explanation
for the data is that the concentration of topically administered corticosteroid that
is absorbed systemically is insufficient to induce reactivation.
Malone and colleagues described a disseminated CHV infection, which led to euthanasia,
in an adult dog.
The dog had undergone chemotherapy for the treatment of generalized lymphoma. It was
not clear whether generalized infection in this case was the result of enhanced susceptibility
to CHV as a result of immunosuppression or whether it was due to reactivation of a
preexisting latent CHV infection in this dog.
Molecular Methods to Detect CHV
Amplification of target sequences by PCR method is currently the most common and most
sensitive molecular diagnostic approach to the detection of CHV in natural or experimentally
infected animals. The PCR assays described initially were gel based, implying that
the amplified products are visualized by UV illumination of ethidium bromide–stained
agarose gels. Miyoshi and colleagues
combined a nested PCR with Southern blotting and showed that the detection limit of
this combination was equivalent to 1 TCID50.
Schultze and Baumgärtner
described nested gel-based PCR and in situ hybridization assays to diagnose acute
CHV infection in formalin-fixed paraffin-embedded tissues of 1- to 3-week-old puppies
that were naturally infected. The specificity of the PCR products was confirmed by
restriction endonuclease digestion. Viral DNA was detected in a variety of cell types,
such as bronchiolar and alveolar epithelial cells, hepatocytes, renal tubular epithelial
cells, neurons, fibrocytes, cardiac myocytes, and endothelial cells. This is in accordance
with the previously described “pantropism” of CHV. When paraffin-embedded tissues
are used for PCR, it has to be kept in mind that the quality of the DNA can be affected
by several factors, such as the length of time between tissue removal and fixation,
the presence of nucleases in the tissue, and the length of storage of the paraffin
Burr and colleagues
developed a gel-based PCR for CHV and used it in conjunction with Southern blotting
to confirm the authenticity of the amplicons. They also assessed the PCR compatibility
of each sample for CHV PCR by first verifying that primers specific for a portion
of the canine pancreatic lipase gene-amplified their target in each of the tissue
extracts. The assay was capable of detecting approximately 14 genomic copies spiked
into 1 μg of placental DNA and approximately 3500 copies when spiked into 0.2 ml of
Erles and colleagues
described a gel-based PCR targeting a 494–base pair region of a gene homologous to
HSV-1 UL 37. Reubel and colleagues
described a nested PCR that had a sensitivity that was 100 times higher than virus
isolation. Ronsse and colleagues
described the use of 2 PCR assays for CHV. One of these assays had a sensitivity of
The most sensitive and specific method currently available to detect CHV DNA is probe-based
real-time PCR. A fluorogenic real-time PCR assay was described by Reubel and colleagues
and reported to have a detection limit of 10 copies of viral DNA. The first probe-based
multiplex real-time PCR for CHV was reported by Ledbetter and colleagues.
Very recently, Decaro and colleagues
reported the development and complete validation of a probe-based real-time quantitative
PCR for the detection and quantitation of CHV DNA in clinical samples. The assay was
found to be very sensitive, since it could detect as few as 10 copies of the target
per sample. In comparison with the gel-based PCR assay described by Schulze and Baumgärtner,
which was used in parallel, this assay has a 10-fold lower detection limit. Specificity
for CHV was very high, as determined by lack of amplification of other canine viruses.
The dynamic range was validated by successful amplification of a number of CHV-positive
samples from different geographic locations. Reproducibility of the assay was determined
by determining both intra-assay and interassay variability between the results obtained
with samples containing variable amounts of target DNA. Both intra-assay and interassay
variability, expressed as a coefficient of variation, were fairly low, were dependent
on the target concentration, and were found to increase with decreasing target copy
numbers. A potential pitfall of PCR assays is that the sample contains substances
that are inhibiting the reaction, thus potentially leading to false-negative results.
To control for this possibility, an internal control construct was spiked into each
sample at known quantity and co-amplified. This way, any inhibition would be readily
detectable from a decrease in the expected signal resulting from the amplification
of this internal control. A relatively simple way to avoid inhibition was to prepare
a 10-fold dilution of the sample.
Since it allows absolute quantitation, the assay was used to determine viral loads
in tissues of pups that had died from acute infection and a vaginal swab collected
from the dam. The viral load in the vaginal swab was 1.57 × 103 copies/10 μl. The
highest viral load in tissues was 5.76 × 109 copies/10 μl, present in kidney homogenates.
The authors concluded that, since it quantitates copy numbers over a wide range, this
assay will be very useful not only for diagnostic purposed, but also for future pathogenesis
studies and for the testing of the effect of antivirals on the replication of CHV.
Carrier States and Shedding Patterns
The phrase “carrier animal” has been used extensively to describe an animal that harbors
an infectious agent beyond the usual time allowed for the incubation phase of the
infection and the acute and convalescent phases of clinical disease.
When it comes to the herpesviruses this is problematic since there are at least 2
phases that exceed those previously mentioned and are characterized by latency and
exacerbation of clinical symptoms from latency. According to Povey, a carrier animal
may or may not shed virus in excretions or secretions, and shedding may occur continuously
As was noted in the preceding section, latency in its strict definition is the lack
of viral transcription and translation, so no mature virus is being produced. A latently
infected dog with CHV would be defined as a carrier dog that is not shedding virus
and would not be contagious to in-contact, susceptible dogs. Exacerbation of the latent
state to a replicative state would result in virus replication and shedding. The dog
may have mild to severe clinical symptoms during this exacerbation phase.
Primary, systemic neonatal CHV infection is associated with extensive viral shedding
from numerous anatomic sites. High CHV viral titers are detected in respiratory secretions,
ocular discharge, saliva, and urine and on many mucosal surfaces (eg, genital, nasal,
ocular, oral, pharyngeal, rectal, tracheal4, 28). Viral shedding may persist for up
to 3 weeks in dogs that survive neonatal infection. Viral shedding from infected neonates
may serve to spread CHV, either through direct contact or fomites, to littermates
and other dogs.
Primary and recurrent CHV infection in mature dogs is associated with mucosal viral
shedding that it detectable by PCR assay or virus isolation. The duration and anatomic
site of shedding vary markedly between dogs and infection episodes in individual animals.
Canine herpesvirus-1 shedding often occurs from multiple mucosal surfaces simultaneously
and may be detected at sites anatomically distant to regions of overt clinical disease.
Reports of experimentally induced primary and recurrent CHV infection suggest viral
shedding during primary infection is prolonged and associated with higher viral titers
than recurrent infection.8, 45, 51, 54 There is an individual dog susceptibility to
CHV reactivation and shedding. Latent CHV infection can be reactivated, with induction
of viral shedding, by short durations of corticosteroid administration in some dogs;
however, other dogs are resistant to corticosteroid-induced viral reactivation.8,
When naturally infected mature bitches that previously aborted CHV-infected pups where
experimentally immunosuppressed by a 5-day course of systemic corticosteroid administration,
CHV was shed from the nasal, oral, ocular, and vaginal mucosa.
Viral shedding could not be induced in all dogs. Viral shedding was detected by virus
isolation as early as 5 days, and as late as 20 days, after initiating corticosteroid
administration. The duration of detected CHV shedding ranged from 1 to 7 days in individual
dogs. In a similar study
using 3-month- and 2-year-old dogs experimentally infected with CHV by nasal and intravenous
routes, CHV reactivation and mucosal viral shedding were repeatedly induced by systemic
corticosteroid administration. Primary oronasal infection was associated with nasal
CHV shedding of approximately 2 weeks' duration. Following recovery from primary infection,
systemic corticosteroid administration induced viral shedding from the nasal, oropharyngeal,
and genital mucosa. The onset of detectable shedding was between 5 and 9 days after
initiating corticosteroid treatment and persisted for up to 32 days with marked variation
between individual dogs. A second round of corticosteroid administration was administered
3 months later and again resulted in viral shedding in some, but not all, dogs. The
duration of viral shedding was shorter in all dogs during the second experimental
reactivation and was associated with a tendency for lower viral titers.
In studies examining ocular CHV infection, a similar pattern of viral shedding is
reported. Experimental primary ocular CHV infection in mature dogs produced by direct
ocular surface inoculation resulted in conjunctival viral shedding that persisted
for 10 days after inoculation.
Virus was detected in conjunctival samples by virus isolation and CHV PCR, and viral
titers peaked 5 days postinoculation. CHV was inoculated into a single eye, but viral
shedding was detected bilaterally in some dogs. Following recovery from primary ocular
infection, viral shedding was not detected over the subsequent 8 months. Experimental
recurrent ocular CHV infection induced by systemic corticosteroid administration to
dogs recovered from primary ocular infection again resulted in viral shedding.
Ocular CHV shedding was detected by PCR assay in 50% of dogs between 10 and 13 days
after administering the first dose of corticosteroid. In comparison to primary ocular
CHV infection, ocular viral shedding associated with recurrent infection was briefer
and viral titers in samples were lower.
Experimental primary CHV genital mucositis in mature dogs, produced by intravaginal
and intrapreputial CHV inoculation, resulted in genital viral shedding that was detected
by virus isolation for up to 20 days.
Several dogs also developed nasal, pharyngeal, and conjunctival viral shedding during
this period. Canine herpesvirus tracheobronchitis induced by intranasal viral inoculation
was associated with viral shedding for up to 18 days.
In the dogs with CHV upper respiratory tract infection, viral shedding from the nasal
mucosa was detected by virus isolation in all dogs and a some had concurrent tracheal
and rectal viral shedding.
Clinical Ecology and Epidemiology
Five Key Questions
The clinical ecology and epidemiology of CHV can be summarized in Table 3. It basically
starts with a series of questions that inquire into the status of the virus, the host,
and the environment with which both are localized.
The critical question is whether CHV infection and disease are of economic concern?
As was mentioned earlier, the reproductive diseases associated with CHV were the initial
driving force behind the recognition of the economic and emotional effects upon dog
owners. While the costs of CHV-associated reproductive diseases have not been reported,
it would be conceivable that a dam that loses an entire litter to CHV would result
in a loss of $10,000, since multiple puppies are involved. In cases of respiratory
disease and ocular disease, the costs of treatment and long-term care of recurrent
infections may exceed $1000 per case.
Clinical ecology and epidemiology of canine herpesvirus infection and disease
1. Is the infection/disease of economic concern?
Yes, may result in high mortality of litters, increased respiratory and ocular disease
in susceptible dogs.
2. Is the infection/disease a public health risk? (zoonosis)
No, restricted host range to the canids.
3. Where is the agent when not causing disease? (ecology)
Subclinical carrier animals, latency. Readily inactivated outside dog's body.
4. What are the key contributing factors to the infection/disease process? (epidemiology)
Naïve susceptible puppies, naïve pregnant dams, and susceptible (stressed) adult dogs.
5. What factors can we control to minimize or eliminate the infection/disease process?
Shedding to susceptible dogs/puppies during critical 6 week danger period; maintain
good kennel biosecurity. No vaccine available.
Data from Evermann JF, Eriks ES. Diagnostic medicine: The challenge of differentiating
infection from disease and making sense for the veterinary clinician. Adv Vet Med
The second question pertains to the zoonotic or public health risks associated with
CHV infections. The virus is species specific and there is no evidence to support
its involvement in human disease.
The third question is the key to the persistence of CHV in the canine population—Where
is the virus when not causing disease? This has been a key factor in understanding
the virus and controlling it. The virus maintains itself in subclinical carrier dogs
by way of latency. It may be exacerbated throughout life by stress, which results
in mild to severe clinical symptoms that most commonly affect the respiratory and
ocular systems. Concurrent with these clinical episodes there is shedding from excretions
and secretions to susceptible dogs. The 2 most susceptible age groups are pregnant
CHV naïve dogs and puppies of these dams (in utero, postnatal).
The fourth question revolves around the epidemiology of CHV once its infection occurs
in the susceptible dog. The course of the infection to disease is variable and has
been reviewed earlier under the contemporary clinical observations. One important
aspect to reiterate here is the importance of immunity in controlling the infection–disease
process in pregnant dams and their offspring during the postnatal period. Early postnatal
infection (3 weeks or less) results in high morbidity accompanied by high mortality.
Later infection (3 weeks or later) results in low morbidity and very low mortality.
However, it is usually the later postnatal infection that establishes the lifelong
carrier state via latency.
The fifth question is a natural extension of the sequence of clinical inquiry and
addresses the control of CHV, so that infection is minimized during disease-susceptible
periods and maximized during disease-resistant periods. As noted previously, shedding
states are important in maintaining the virus infection on the population to attain
a certain degree of population immunity. Knowing when dogs are potentially contagious,
and maintaining the 6-week barrier to infection, allows for maximum protection during
this susceptible period. Since there is no reliable vaccine available, kennel hygiene
and biosecurity are essential.
Therapy for neonatal CHV infection is largely supportive and carries a poor prognosis
for survival once clinical disease is manifested.
In instances where dogs survive neonatal CHV infection, cardiac, neurologic, and ocular
lesions may be permanent. Elevating the environmental temperature of dogs in a litter
after CHV infection is diagnosed may provide some protection to uninfected pups. Viral
replication is reduced at elevated body temperatures and there are lower morbidity
and mortality rates in dogs that are subsequently infected; however, this is ineffective
for individual dogs if implemented after viral infection.
Intraperitoneal injection of immune sera obtained from CHV-seropositive dogs is described
as a method to reduce mortality in an exposed litter, but it must be administered
prior to infection to be most effective.
Lactoferrin possesses in vitro antiviral activity against CHV and inhibits cellular
Administration of lactoferrin to dogs at risk for infection could theoretically provide
protection; however, this is not demonstrated in vivo. Isolated reports of apparently
successful therapy of neonatal CHV infection with the antivirals vidarabine and acyclovir
are described. Acyclovir was administered orally as a 10-mg total dose per dog at
6-hour intervals until 3.5 weeks of age.
The pharmacokinetics and tissue distribution of intravenous, subcutaneous, and oral
acyclovir were investigated in dogs.57, 58 Additionally, a sustained release buccal
tablet form of acyclovir was evaluated in the dog.
Acyclovir is bioavailable when administered orally to dogs and is widely distributed
within tissues; however, target plasma concentrations and effective dosages for CHV
infection are currently unknown.57, 58, 59 Acyclovir toxicosis resultant from accidental
ingestion is reported in dogs with dosages as low as 40 mg/kg and the routine clinical
use of this, and other systemic antiviral medications, in dogs for CHV infection requires
further investigation of safety and efficacy.
The canine pharmacokinetics of newer-generation anti-herpesviral drugs, including
famciclovir, are reported. Similar to acyclovir, safe and effective doses for dogs
with CHV infection are undetermined.
Treatment of respiratory and genital CHV infection is primarily symptomatic. Unless
complicated by secondary bacterial infection, these conditions are typically self-limiting
and specific antiviral therapy is not reported. In contrast to respiratory and genital
infection, there are detailed reports of the successful clinical management of ocular
CHV infection. In addition to nonspecific treatments to prevent secondary bacterial
infection (topical ocular antimicrobials) and improve comfort (topical ocular atropine),
antiviral therapy with 0.1% idoxuridine or 1% trifluridine ophthalmic solution was
used. Idoxuridine and trifluridine are nucleoside analogues, possess good anti-herpesvirus
activity, and are well tolerated by dogs when applied topically as ocular formulations.
Trifluridine is available under the trade name Viroptic, and idoxuridine can be acquired
from compounding pharmacies. Both antivirals are administered 6 to 8 times daily for
the first 48 hours and then 4 times daily until resolution of clinical signs of active
infection. Cidofovir 0.5% ophthalmic solution is an alternative ophthalmic antiviral
for CHV ocular disease that is effective with twice daily administration (E.C. Ledbetter,
unpublished data, 2011).
This review has documented well that our level of clinical inquiry expands as our
knowledge base about CHV increases. While earlier studies focused on the reproductive
effects of CHV in susceptible pregnant dogs and neonatal puppies, it has become apparent
that in order to control CHV-related diseases that we must understand the various
forms of CHV infection that may occur in the dog population (Fig. 7). This has prompted
the veterinary community to develop more sensitive diagnostic assays, such as PCR,
in order to answer the questions, where is the virus when not causing disease, and
what is its relationship with respiratory and ocular diseases in adolescent and adult
dogs (1 year or older)?
Schematic of the potential interactions amongst three subpopulations of dogs and the
infection-disease cycles of CHV.
Molecular and serologic studies have clearly demonstrated that we are dealing with
an infection that is more common than we considered a decade ago. Reports have indicated
that up to 70% of some high-risk dog populations have been infected with and are latent
carriers of CHV. This is important for veterinarians to know as we confer with clients
on the best management steps we can take to protect our at-risk populations. While
pregnant CHV-naïve dams and neonatal puppies born from a CHV-naïve dam are considered
at high risk for disease, we must also take into consideration dogs in kennels and
rescue centers. It is these dogs that are at risk for either exposure-infection or
stress-induced exacerbation of latent CHV, which had been acquired at an earlier age.
The manifestations of CHV in adolescent and mature dogs may range from subclinical
to severe respiratory and/or ocular diseases. The reports by Malone and colleagues,
Gadsden and colleagues (submitted, 2011), and Ledbetter and colleagues7, 47 all indicate
that CHV can cause disease in older dogs and that it is not just a “puppy disease.”
Recognition of the various forms of CHV-induced disease, availability of diagnostic
assays with increased sensitivity, and the formation of reliable biosecurity measures
will allow for better control steps to be taken in dogs at-risk for infection and