Canine Distemper

Canine Distemper

ETIOLOGY

Canine distemper virus (CDV) is a member of the genus Morbillivirus of the family Paramyxoviridae.

Various strains differ in their pathogenicity, which may affect the severity and extent or type of clinical disease. Certain isolates, such as Snyder Hill, A75/17, and R252 strains, are highly virulent and neurotropic. CDV has the ability to cause CNS disease.

Susceptibility

·         CDV is susceptible to ultraviolet light.

·         Extremely susceptible to heat and drying, CDV is destroyed by temperatures of 50 ° C to 60 ° C for 30 minutes.

·         It survives for at least an hour at 37 ° C and for 3 hours at 20 ° C (room temperature).

·         At near-freezing (0 ° C to 4 ° C), it survives in the environment for weeks. Below freezing the virus is stable, surviving at − 65 ° C for at least 7 years.

·         CDV remains viable between pH 4.5 and 9.0.

·         As an enveloped virus, it is susceptible to ether and chloroform, dilute (less than 0.5%) formalin solution, phenol (0.75%), and quaternary ammonium disinfectants (0.3%).

·         Routine disinfection procedures are usually effective in destroying CDV in a kennel or hospital.

·         The disease and natural host ranges of CDV include certain species of terrestrial carnivores, and other species can be infected experimentally with varying degrees of susceptibility.

Host

·         Inapparent, self-limiting infections, produced in domestic cats, nonhuman primates, and humans by parenteral inoculation of virulent CDV, resemble those in dogs that have been given modified live virus (MLV) vaccines.

·         Nonhuman old-world primates (Macaca fuscata and Macaca mulatta) have been naturally infected.

·         Despite the wide host range, dogs are the principal reservoir host for CDV, and they likely act as reservoirs of infection for wildlife.

·         It can occur in dogs of any age, but it most commonly affects unvaccinated, exposed puppies 12 to 16 weeks of age that have lost their MDA or younger puppies that have received inadequate concentrations of maternal antibody.

EPIDEMIOLOGY

Viral shedding occurs by 7 days following infection. CDV is commonly spread by aerosol or droplet exposure; however, it can be isolated from most other body tissues and secretions, including urine.

Transplacental infection can occur from viremic dams.

Virus can be excreted up to 60 to 90 days after infection, although shorter periods of shedding are more typical.

Contact among recently infected (subclinical or diseased) animals maintains the virus in a population, and a constant supply of puppies helps provide a susceptible population for infection.

Although immunity to virulent canine distemper is prolonged or lifelong, it is not as absolute after vaccination. Dogs that do not receive periodic immunizations can lose their protection and become infected after stress, immunosuppression, or contact with diseased individuals.

Many susceptible dogs can become subclinically infected but clear the virus from the body without showing signs of illness. Although most recovered dogs clear the virus completely, some may harbor virus in their CNS. The prevalence rate of spontaneous distemper in cosmopolitan dogs is greatest between 3 and 6 months of age, correlating with the loss of maternal-derived antibodies (MDAs) in puppies after weaning. In contrast, in susceptible, isolated populations of dogs, the disease is severe and widespread, affecting all ages.

PATHOGENESIS

Systemic Infection During natural exposure, CDV spreads by aerosol droplets and contacts epithelium of the upper respiratory tract.

Within 24 hours PI, it multiplies in tissue macrophages and spreads in these cells via local lymphatics to tonsils and bronchial lymph nodes.

By 2 to 4 days PI, viral numbers increase in tonsils and retropharyngeal and bronchial lymph nodes.

By days 4 to 6 PI, virus multiplication occurs within lymphoid follicles in the spleen, the gut-associated lymphatic tissue of the lamina propria of the stomach and small intestines, the mesenteric lymph nodes, and the Kupffer ’ s cells in the liver.

Widespread virus proliferation in lymphoid organs corresponds to an initial rise in body temperature and leukopenia between days 3 and 6 PI.

Further spread of CDV to epithelial and CNS tissues on days 8 to 9 PI probably occurs hematogenously as a cell-associated and plasmaphase viremia and depends on the dog ’ s humoral and cell-mediated immune status. Shedding of virus from all body excretions begins at the time of epithelial colonization, even in dogs with subclinical infections.

By day 14 PI, animals with adequate CDV antibody titers and cell-mediated cytotoxicity clear the virus from most tissues and show no clinical signs of illness.

Dogs with intermediate levels of cell-mediated immune responsiveness with delayed antibody titers by days 9 to 14 postinfection have viral spread to their epidielial tissues. Clinical signs that develop may eventually resolve as antibody titer increases and virus is cleared from most body tissues. However, complete virus can persist for extended periods in uveal tissues and neurons and in integument such as footpads.

The pathogenesis of replication and persistence of CDV in footpads has been well investigated. Microscopic lesions consist of hyperkeratosis and parakeratosis with vesicle, pustule, and inclusion body formation. Virus entering the footpad epithelium during the viremic period causes proliferation of basal keratinocytes, resulting in the observed hyperkeratosis; however, neither the virus nor its nucleic acid appears to persist indefinitely. This epidermal localization has been associated with certain wild-type CDV strains that produce noncytocidal infection in footpad keratinocytes in vitro and experimentally infected dogs. Cytokine expression is upregulated in virus-infected footpad epidermal cells.

Recovery from CDV infection is associated with long-term immunity and cessation of viral shedding.

By days 9 to 14 PI, dogs with poor immune status undergo viral spread to many tissues, including skin, exocrine and endocrine glands, and epithelium of the gastrointestinal (GI), respiratory, and genitourinary tracts.

Clinical signs of disease in these dogs are usually dramatic and severe, and virus usually persists in their tissues until death. The sequence of pathogenic events depends on the virus strain and may be delayed by 1 to 2 weeks.

Secondary bacterial infections increase the severity of clinical illness.

Prenatal and neonatal distemper infections are causes of immunodeficiency in surviving puppies and can make concurrent infections with other viruses such as parvovirus, bacteria such as Clostridium piliforme , or protozoa such as Neospora caninum more severe.

In surviving animals, CDV is cleared from the inflammatory lesions but can persist in brain tissue in unaffected sites.

CLINICAL FINDINGS

Systemic Signs

Clinical signs of canine distemper vary depending on virulence of the virus strain, environmental conditions, and host age and immune status.

More than 50% of CDV infections are probably subclinical.

Mild forms of clinical illness are also common, and signs include:

·         Listlessness,

·         Decreased appetite,

·         Fever, and upper respiratory tract infection.

·         Bilateral serous oculonasal discharge can become mucopurulent with coughing and dyspnea.

·         Pneumonia,

·         Keratoconjunctivitis sicca

·         Persistent anosmia

·         A mild, serous-to-mucopurulent conjunctivitis,

·         Dry cough that rapidly becomes moist and productive.

·         Depression and anorexia are followed by vomiting,

·         Diarrhea subsequently develops, varying in consistency from fluid to frank blood and mucus.

·         Tenesmus

·         Intussusceptions can occur.

·         Severe dehydration and emaciation

·         Animals can die suddenly

·         Vesicular and pustular dermatitis in puppies

·         Nasal and digital hyperkeratosis

·         Hyperesthesia and cervical or paraspinal rigidity

·         Seizures, cerebellar

·         paraparesis or tetraparesis with sensory ataxia, and myoclonus are common.

·         The “ chewing-gum ” type of seizures, classically associated with CDV infection,

·          

Neurologic manifestations usually begin 1 to 3 weeks after recovery from systemic illness; however, no way is known to predict which dogs will develop neurologic disorders. Neurologic signs can also coincide with multisystemic illness, or less commonly, they can occur weeks to months later.

With more extensive spinal cord damage, the dog may have upper motor neuron paresis of the affected limb associated with myoclonus.

Transplacental Infection Young puppies infected transplacentally may develop neurologic signs during the first 4 to 6 weeks of life.

Puppies infected in utero that survive such infections may suffer from permanent immunodeficiencies because of damage to primordial lymphoid elements.

Neonatal Infections Young puppies infected with CDV before the eruption of permanent dentition can have severe damage to the enamel, dentin, or roots of their teeth.

THERAPY

Supportive and nonspecific, aims in treatment are frequently beneficial because they reduce mortality.

Dogs with upper respiratory infections should be kept in environments that are clean, warm, and free of drafts.

Oculonasal discharges should be cleaned from the face.

Pneumonia is frequently complicated by secondary bacterial infection, usually with Bordetella bronchiseptica , which requires broad-spectrum antibacterial therapy and expectorants or nebulization and coupage. Good initial antibacterial choices for bronchopneumonia include ampicillin, tetracycline, and chloramphenicol. Parenteral florfenicol might be considered if this is a concern. However, because of dental staining, tetracycline use must be avoided in puppies, and chloramphenicol is less desirable because of its public health risks. Parenteral therapy is essential when GI signs are present.

Food and water and oral medications or fluids should be discontinued if vomiting and diarrhea are present.

Parenteral antiemetics may be required.

Supplementation with polyionic isotonic fluids such as lactated Ringer ’ s solution should be given intravenously or subcutaneously, depending on the hydration status of the patient.

B vitamins should be administered as nonspecific therapy to replace vitamins lost from anorexia and diuresis and to stimulate the appetite. Anecdotally, intravenous administration of ascorbic acid can be beneficial; however, this treatment is controversial, and its effectiveness remains unproven.

Two 200,000-IU (60-mg) doses of vitamin A within 5 days of the onset of systemic illness can be given though its efficacy is not proven. A similar regimen of vitamin A, given early in the course of disease, could be tried for puppies with acute systemic infection.

Therapy for neurologic disturbances in canine distemper is less rewarding.

Variable or temporary success in halting neurologic signs in some dogs can result from a single anti-CNS edema dose (2.2 mg/kg, given intravenously of dexamethasone.

Subsequent maintenance therapy with anti-inflammatory doses may be needed, and this treatment can be tapered with time.

Seizures, myoclonus, or optic neuritis are three neurologic manifestations in. Myoclonus is usually untreatable and irreversible. Drugs such as benzodiazepines or levetiracetam have been used with variable efficacy.

Seizures are best treated with parenteral diazepam (0.5- to 2-mg/kg rectally or slow IV) for status epilepticus and phenobarbital for maintenance prevention.

Primidone or potassium bromide is alternative choices, and combinations or higher doses may be needed in refractory cases.

Glucocorticoid therapy in anti-inflammatory to anti-CNS edema dosages may have variable success in controlling the blindness or papillary dilation from optic neuritis or the other neurologic signs.

PREVENTION

Immunity to natural CDV infection is considered long term, and lasting immunity and immunologic homogeneity of the virus have made disease prevention possible through vaccination. MDA, received in utero and in colostrum from the dam, blocks adequate immunization in puppies for a period after birth and a period after weaning. MDA to CDV decreases with a half-life of 8.4 days. Three percent of antibody transfer for CDV occurs in utero, and 97% occurs in the colostrum, resulting in an initial titer in nursing newborn puppies that is usually equal to 77% of that in the bitch. A puppy that has not received colostrum is probably protected for at least 1 to 4 weeks.

MDA are usually absent by 12 to 14 weeks of age.

Vaccines for CDV are generally given every 3 to 4 weeks between 6 and 16 weeks of age in puppies that have received colostrum.

Immunity after recovery from natural infection or after booster vaccination can persist for years. This protection can be adequate unless the dog is exposed to a highly virulent strain of virus or large quantities of virus or becomes stressed or immunocompromised.

After a single distemper vaccination, naïve puppies may not develop sustained immunity. Therefore, despite the lack of MDA interference, at least two distemper vaccines should be given at 2- to 4-week intervals when first vaccinating colostrum-deprived neonates and in dogs older than 16 weeks. Similarly, and because older vaccinated dogs can still develop distemper, periodic boosters are recommended for this disease, despite the relatively long-lived immunity afforded by vaccination.

Vaccination with attenuated virus appears to protect previously unvaccinated dogs when it is given intravenously at least 2 days before exposure to virulent CDV, as compared with at least 5 days with subcutaneous vaccination.

One dose of vector recombinant CDV vaccine also protected 10- to 12-week-old pups against clinical illness when they were challenged with virulent virus by intravenous or contact exposure to infected dogs, 1 week or 4 hours, respectively, after vaccination.

The recombinant poxvirusvectored vaccine is the safest.

Dogs younger than 6 weeks with very high MDA concentrations (serum-neutralizing antibody titer greater than 300) do not respond well to distemper vaccination.

If female puppies are vaccinated with measles vaccine after 12 weeks of age, they will passively transfer measles antibody to their off spring, especially if they are bred during the first heat cycle.

Vaccine stability

Lyophilized tissue culture vaccines are stable for 16 months under refrigeration (0 ° C to 4 ° C), 7 weeks at 20 ° C, and 7 days when exposed to sunlight at 47 ° C. When reconstituted, tissue culture virus remains stable for 3 days at 4 ° C and 24 hours at 20 ° C. Vaccine should be used immediately once it is reconstituted for injection, or it should be refrigerated if the delay until use will be longer than 1 hour.

Adverse environmental influences can affect the response to distemper vaccination in dogs. High ambient humidity (85% to 90%) and high temperatures that cause dogs to have rectal temperatures averaging 39.8 ° C (103.6 ° F) can reduce the immune response after distemper vaccination.

Antigenic drift of wild-type CDV strains might cause distemper outbreaks in domestic dog and wild animal populations.

The broad host range of potential reservoirs makes eradication of this disease difficult.

First, every attempt should be made to achieve the highest vaccination rate possible in domestic dogs, especially in areas where they cohabitate or live near feral or wild animal populations. The most potent vaccines that can be tolerated without producing vaccine-induced illness should be used.

Serum Antibody Monitoring and Duration of Immunity to MLV canine distemper vaccines is longer than 1 year, despite vaccine label recommendations that annual vaccination of dogs be performed.

The American Veterinary Medical Association and American Animal Hospital Association recommendations are for 3-year intervals after the initial series and a booster 1 year later.

The clinician should decide whether to provide more frequent vaccination based on the animal and environmental considerations. Serum-neutralizing antibody titer greater than or equal to 100 is considered protective when the dog has received maternal antibodies. A serum-neutralizing antibody titer of 20 is considered protective when measuring a vaccination response.

Dogs with prior vaccination intervals of greater or equal to 3 years shows declining antibody titers.

Infected animals are the primary source of the virus, so they should be segregated from other healthy dogs. Dogs usually shed the virus in secretions for 1 to 2 weeks after the acute systemic illness. Those recovering from systemic illness or that are developing later neurologic signs (without systemic disease) can still be shedding some virus.

PUBLIC HEALTH CONSIDERATIONS

Some have suggested that Paget’s disease, an inflammatory bone disorder in humans, might be related to CDV acquired from exposure to dogs.

Owning a dog was found to be highly correlated with Paget’s disease, but this indirect relationship should not be overstated because a similar correlation was found between Paget’s disease and ownership of cats and birds.