CANINE HERPES VIRAL INFECTION (CHV)

Introduction
Canine herpesvirus is a fatal, viral infection of puppies worldwide. It also may be associated with upper respiratory infection or a vesicular vaginitis or posthitis in adult dogs. Only canids (dogs, wolves, coyotes) are known to be susceptible.

Etiology
The disease is caused by an enveloped DNA canine herpesvirus (CHV), which is sensitive to lipid solvents and most disinfectants. CHV is relatively unstable outside the host. Transmission usually occurs by contact between susceptible puppies and the infected oral, nasal, or vaginal secretions of their dam or oral or nasal secretions of dogs allowed to commingle with puppies during the first 3 wk of life. In utero transmission may occur. Infection of newborn susceptible puppies results in replication of CHV in the surface cells of the nasal mucosa, pharynx, and tonsils. If the pups become hypothermic, viremia and invasion of visceral organs occur.


Clinical Signs
In very young puppies include:

  • anorexia

  • soft stools progressing to diarrhoea

  • painful abdomen: the puppies cry continually with paddling limb movements until they die

  • sometimes dyspnoea; vomiting or salivation


  • Most puppies less than 2-3 weeks old die within 1 or 2 days of onset of clinical signs

  • Sudden death in very young puppies may be due to CHV infection

  • ‘Fading puppy syndrome'

  • Puppies over 2 weeks old seldom become severely ill, but may develop respiratory signs

  • Occasionally vesicular lesions on male and female genitalia in adults

  • Abortion or stillborn puppies from bitches infected during pregnancy

  • Most infection of adults is subclinical

Clinical Findings
Deaths due to CHV infection usually occur in puppies 1-3 wk old, occasionally in puppies up to 1 month old, and rarely in pups as old as 6 months. Typically, onset is sudden, and death occurs after an illness of 24 hours. Older dogs exposed to or experimentally inoculated with CHV may develop a mild rhinitis or a vesicular vaginitis or posthitis. In utero infections may be associated with abortions, stillbirths, and infertility.

Diagnosis
CHV infection may be confused with infectious canine hepatitis, but it is not accompanied by the thickened, oedematous gallbladder often associated with the latter. The focal areas of necrosis and haemorrhage, especially those that occur in the kidneys, distinguish it from hepatitis and neosporosis. CHV causes serious disease only in very young puppies. The rapid death and characteristic lesions distinguish it from canine distemper. The virus can be isolated from fresh lung, liver, kidney, and spleen by cell culture techniques. The tissues should be submitted to the laboratory refrigerated but not frozen.


Control
No vaccine is available. Infected bitches develop antibodies, and litters subsequent to the first infected litter receive maternal antibodies in the colostrum. Puppies that receive maternal antibodies may be infected with the virus, but disease does not result. Removal of puppies from affected bitches by caesarean section and rearing them in isolation has prevented deaths under experimental conditions. However, infections have been noted even in puppies delivered by caesarean section. Deaths may be reduced when infected puppies are reared in incubators at increased temperatures (95°F [35°C], 50% relative humidity) and given adequate fluids and supportive therapy. The prognosis of puppies that survive neonatal infections of CHV is guarded because damage to lymphoid organs, brain, kidneys, and liver may be irreparable.

CANINE HERPES VIRUS INFECTION 

Clinical signs

In adult dogs 

  • Discrete or unapparent signs (transient papulovesicular lesions on external genital system).

  •  Pain during mating (irregular but linked to the presence of lesions in one of the animals). 

  • Reproduction disorders (fertilization and nidation disorders; more rarely, abortions). 

In puppies aged less than 3 weeks

  • Neonatal mortality (viraemia): anorexia, chill, abdominal pain, groaning, bicycling and death with episthotonos within a few days.

  • Rhinotracheitis in puppies aged more than 15 days.

  • More rarely, ocular disorders (keratitis, iridocylitis).

Definition

  • Frequent and cosmopolitan disease in dog breeding due to a canine herpesvirus (CHV) and causing neonatal mortality and different disorders of the reproductive cycle (infertility, abortions). Seroprevalence is very high (48% of breeding facilities with outbreaks of infertility or neonatal mortality show high seropositivity).

Causes

  • Encapsulated virus (like feline rhinotracheitis virus), opportunistic and low immunogenic activity, with tropism for both respiratory and genital mucous membranes and central nervous system, capable of persisting in a latent status and reactivating at regular intervals.

  • Main sources of viral contamination: all secretions and excretions (vaginal mucus, sperm, expectorations, saliva, urine, and faeces) as well as foetuses and foetal membranes. 

  • Main sources of infection: transmission via the venereal, transplacental and oronasal (direct contact) routes.

Predisposting factors

  • All immunosuppressed dogs (stress, cold, oestrus in females). 

  • Puppies, from birth up to 15 days of age. 

  • Kennel cough (enhancing the airborne of spread virus).

Presumptive diagnosis

  • Any outbreak of neonatal mortality (within eight days following birth) affecting the litter of one breed in particular within a multi-breed facility, and rarely involving the same breeding bitch over two consecutive reproductive cycles is evocative of a primary canine herpesvirus infection. 

  • Investigation into a "hypo-fertility" or "infertility" syndrome during breeding must include possible sequelae of CHV infection within the breeding facility. 

  • History of rhinotracheitis or genital lesions in breeding dogs. 

  • Absence of macroscopic lesions in case of fulminant forms (so-called "blank" post-mortem examination). 

  • Necrohaemorrhagic foci on lungs and renal cortex (nutmeg appearance). 

Confirming diagnosis

In the mother

  • During viral reactivation periods (15 days post-partum, oestrus): 

  • Seroneutralisation on puppy kidney cell cultures (collection in dry tube (no anticoagulant) of two samples of the mother's serum at 10-15 day interval, the first sample being collected in the days following abortion or stillbirths).

  • ELISA (less sensitive but faster). 

In puppies

  • Intranuclear inclusions, although rarely detected by histological examination of different organs (kidney, liver, lungs, spleen). 

  • Meningoencephalitis lesions revealed by histological examination. 

  • Direct immunofluorescence on puppy kidneys (frozen within two hours after death). 

  • PCR on lungs and kidneys. 

  • Meningoencephalitis lesions revealed by histological examination. 

  • Direct immunofluorescence on puppy kidneys (frozen within two hours following death). 

  • PCR on puppy lungs and kidneys (specialist laboratories).

Differential diagnosis

  • Fading Puppy Syndrome (in which CHV is probably involved). 

  • Any other syndrome causing neonatal mortality (e.g. toxic milk syndrome, mycoplasmosis, neonatal septicaemia). 

  • Brucellosis.

Prognosis

  • Prognosis improves with the age of puppies and their increasing thermoregulation ability. 

  • Prognosis is related to the latent and reactivation capacity of all known herpesviruses. Viral reactivation periods in bitches (oestrus, whelping) are better documented that in male dogs (immunosuppression). Despite low CHV pathogenicity, viral reactivation does not usually come with neonatal mortality (transmission of neutralising antibodies through the colostrum, and covering the "critical period" for puppies). 

  • Tendency to self-regulation in a previously infected breeding facility. 

  • During the following pregnancy, colostral antibodies can protect puppies against the infection but not from virus carriage and re-excretion. 

  • Treatment is illusive after the onset of clinical signs in puppies. 

  • Hypothermia seems to enhance CHV infection in newborn puppies (insufficient immune response in hypothermic puppies). In such cases, the breeder could:

•  Dry the puppies at risk immediately after birth (puppies born to primary infected mothers) to limit the drop in temperature related to the evaporation of amniotic fluid or licking by the mother ("air conditioning" effect). 

•  Place the puppies in an incubator or poultry incubator with high hygrometry between suckings.

Prevention

  • The CHV virus is sensitive to most physical (heat > 37°C, UV light) and chemical agents (enzymatic disinfectants, quaternary ammonium compounds, biguanides/diguanides, formalin derivatives, natural or synthetic phenols, bleach, etc.). They can however resist cold temperatures (even in frozen semen). 

  • A vaccine has recently been developed and authorized for marketing. Its objective is to stimulate the production of seroneutralising antibodies in pregnant bitches so as to induce the passive protection of newborn puppies through colostral transmission. The vaccine must be administered as two injections, the second one being given 10 days before whelping in order to obtain the best antibody transmission. 

  • Injection of homologous serum to puppies at risk (serum collected from hyperimmune mothers). 

  • Prevention of venereal transmission from female to male using artificial insemination. 

  • Pre-partum administration of vaginal antiseptic to primary infected bitches during pregnancy in order to reduce the vaginal virus load. 

  • Limitation of risks of male to female contamination by temporarily excluding male dogs showing suspicious lesions from breeding. 

 HERPES VIRUS INFECTION

Canine herpesvirus is generally referred to as CHV, and is a leading cause of puppy deaths, especially in puppies one to three weeks of age. We have all heard of breeders saying something like this - 'The puppies were fine this morning, but then they stopped eating and died before I could do anything!' Anytime puppies die in this fashion, there is a reason to suspect CHV. 

Transmission
Canine herpesvirus is a viral disease that affects many puppies, causing sporadic deaths and occasionally the death of an entire litter. The virus lives in the reproductive and respiratory tracts of male and female dogs and can be sexually transmitted. The virus persists in the female's vaginal secretions and the male's semen. As in many herpes infections found in other species, adult animals can live for years with no apparent signs; these are called 'asymptomatic carriers.' This means the adult male and female dogs can remain infected and transmit the disease for years while showing no signs of disease themselves.

Puppies can become infected several ways. The virus can cross the placenta and infect them while they are still within the uterus, or they may become exposed from vaginal secretions during birth. The virus can also become airborne from nasal secretions of the mother, so once born, the pup can actually inhale the virus while breathing. Puppies can easily spread the virus from one to another. Lastly, the virus can be transmitted by eating infected materials.

Symptoms
Once exposed, it generally takes about a week for symptoms to appear. With this in mind, you can easily see why 1 to 3 week-old puppies are at the highest risk. Severely infected individuals will become depressed, stop nursing, and cry. Their feces will be soft and yellow-green. Their livers enlarge and their abdomens are painful. The liver becomes damaged and can no longer function normally. Some puppies develop respiratory signs and nasal discharge. Others develop a rash on their abdomen. Hemorrhages such as nose bleeds and small bruises on the mucous membranes or skin may appear. Some puppies will show nervous system signs such as blindness and staggering. Puppies usually die within 24-48 hours of showing signs of disease.

Not all pups exposed at birth become ill, and many show no signs at all or develop only a slight congestion and recover within a few days. Puppies exposed after six weeks of age have a better chance of recovery. Older puppies develop the disease by coming in contact with the mother's infected, but normal-appearing, nasal secretions. Those that live often develop into carrier adults just like their parents.

It appears that the virus thrives best at a temperature of around 99ºF, so this may help to explain why older puppies are at less risk since their body temperature is usually around 101.5ºF, and that of younger puppies is lower.

Adult carriers typically exhibit no obvious symptoms, however, small blister-like lesions may occasionally be noted on the vaginal wall.

Making a diagnosis
Canine herpesvirus is one of the leading causes of death in newborn puppies. Once the above signs develop, death often follows in 48 hours. The disease spreads rapidly through the litter as infected puppies are highly contagious. We suspect many cases of herpes are wrongly diagnosed as disorders such as parvovirus and coronavirus.

Autopsies of deceased puppies by a veterinary pathologist will reveal the characteristic herpes lesions. Diagnostic hemorrhagic lesions will be found within the kidney and liver, and the lungs will usually be congested. The affected organs will have cells containing characteristic signs of the disease.

Treatment and prevention
Currently there is no specific treatment for canine herpes. All treatment is aimed at supportive care. Older puppies can be force-fed and treated with anti-diarrheal medication. The survival rate of puppies less than three weeks old is poor. Severely infected puppies will die rapidly. The remaining puppies should be kept warm (100ºF) until the virus has run its course. It is hoped that a vaccination will be developed to protect against this disease.

As a preventive practice, one should make sure the environmental temperature of the puppies is kept warm with whelping boxes, heat lamps, etc.

In conclusion, anytime one sees upper respiratory infections in puppies less than 8 weeks of age, CHV should be considered. Also, CHV is a leading cause of death in 1 to 3 week-old pups, and even older puppies may die. The deaths will occur suddenly, with little or no warning, and one pup or even an entire litter may perish within a 24-hour period. This is especially disheartening when yesterday the litter appeared happy and healthy, and today some are ill or have already died. Remember, the mother may be a carrier and future litters may be affected unless she develops a natural immunity. There is no treatment for her or for the puppies.


Race Foster, DVM
Marty Smith, DVM
Drs. Foster & Smith, Inc.
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