23 Dec 2021
Simon Tappin MA, VetMB, CertSAM, DipECVIM-CA, FRCVS details prevention strategies, diagnosis and treatment for distemper, parvovirus and canine infectious hepatitis.
Simon Tappin
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Image: © Tierfoto-Graf / Adobe Stock
Vaccination has historically formed the cornerstone of small animal practice, with its use dramatically reducing the incidence of many viral diseases that were once very common and very often fatal.
Uptake of regular vaccination has waned recently, with regular annual vaccination becoming controversial and the development about vaccination safety, especially in the wake of the controversy surrounding the human MMR vaccine.
Canine travel has also brought animals bearing infection to the UK, which has left challenges in diagnosis and management.
This article examines each of the core viruses that we vaccinate for, and discusses the diagnosis, treatment and vaccination strategies for each.
The canine distemper virus (CDV) is a large, enveloped, single‑stranded RNA virus that is closely related to the measles virus.
The incidence of distemper has reduced dramatically – from the most fatal infectious disease of dogs, to very low levels since the introduction of modified live vaccines in the 1960s.
Cases in the US and Europe have slightly increased in recent years due to a decrease in the proportion of dogs vaccinated and vaccine breakdown.
Only one serotype of distemper exists, although different strains have been identified with small antigenic variations that vary markedly in their pathogenicity.
Distemper is readily inactivated by heat, light and disinfectant, and does not survive long outside the body.
Most terrestrial carnivores are susceptible to distemper – this includes dogs, foxes, ferrets, mink, otter, badgers, raccoons and large cats (lions, tigers and leopards).
Distemper contributed to the near‑extinction of the black-footed ferret and played a role in the extinction of the Tasmanian tiger. In the early 90s, lion numbers in the Serengeti reduced by 20% as a result of the infection. The disease has mutated to form phocid distemper, which affects seals.
Distemper can affect dogs of all ages, but is most common in dogs younger than one year of age; usually after maternal antibodies have waned.
Disease is most commonly seen in areas of low vaccination rates, and high‑density areas such as rescue centres tend to perpetuate the infection.
No zoonotic risk exists, although an association with Paget’s disease in humans has been postulated.
Clinical signs vary widely and infection may be subclinical in some cases. Mild pyrexia, inappetence and depression with a serous or mucopurulent ocular and/or nasal discharge can progress to gastrointestinal signs and lower respiratory tract disease. CNS signs may follow in some cases, as can more chronic signs such as hyperkeratosis (“hard pad”) and marked weight loss. In growing animals, hypoplasia of the tooth enamel may also be seen.
Secondary bacterial infection, especially those involved in kennel cough, can occur and carry up a poorer prognosis.
Other opportunistic infections – such as nocardiosis, toxoplasmosis and generalised demodicosis – have also been reported.
CNS signs may be delayed for months to years and result in encephalitis in the mature or older dog, sometimes without a history of pre‑existing signs of distemper. This occurs when a virus remains present in the CNS for long periods, despite elimination from the rest of the body.
Distemper has been isolated from dogs with metaphyseal osteopathy, although a causal relationship has not been documented.
Transplacental infection with CDV may be associated with infertility, stillbirth and abortion; puppies can be born with neurological signs that develop at four to six weeks of age.
Gross postmortem changes are variable and often inconclusive. Histopathological diagnosis is possible if eosinophilic intracytoplasmic inclusion bodies can be documented in epithelial tissue. The respiratory and bladder mucosa are the best sites. Changes in the lymphoid tissue and respiratory tract may also be helpful. Immunofluorescence tests for antigen in lymphoid tissue, lung and brain can also be useful.
In the live animal, diagnosis can be difficult. CDV is readily isolated in cell culture and cytopathic effects are normally seen within 24 hours; unfortunately, as a diagnostic test, virus isolation is fairly impractical.
PCR is the most sensitive test using mononuclear cells in the buffy coat, conjunctival smears or bronchial washes. Immunocytochemistry may also help improve diagnosis on cytological samples.
CSF analysis in cases with neurological signs reveals increases in protein and mononuclear cells. Antigen may be detected by PCR in acute cases; the presence of antibody is diagnostic in animals with an intact blood brain barrier.
Serology may be difficult to interpret as immunosuppression may prevent a rising antibody titre, although a fourfold increase in antibody in a not recently vaccinated dog is diagnostic for distemper. It can also be useful to look at IgM as this remains elevated for three months after infection, but only three weeks after vaccination.
In the absence of specific antiviral treatments, therapy is largely supportive and symptomatic, with the aim of controlling the clinical signs for each patient. Non‑specific supportive therapy includes antibiotic therapy (broad‑spectrum therapy to protect again the effects of immunosuppression), fluid therapy and careful nursing. Sedatives and anticonvulsants can be used in neurological cases; however, the prognosis in these cases is poor and where progressive signs are present, euthanasia should be considered.
Vaccination programmes using modified live vaccines have greatly reduced the prevalence of distemper in the UK. These are either derived from avian cell culture (Onderstepoort strains) or canine cell culture (Rockborn strain). The Rockborn strain produces a more rapid response, but is associated with higher levels of post‑vaccine encephalitis (especially in miniature schnauzers) and is, therefore, no longer used in the UK.
Live vaccines can also be fatal in certain zoo animals, such as red pandas and black‑footed ferrets.
Historically, measles vaccines (canine products; not the human counterpart) have been used to provide protection against distemper to puppies with high maternally derived antibody, with fair success.
In a kennel or rescue centre situation, management and disinfectant machines can be extremely effective in control as the virus does not survive well outside the body and is very sensitive to disinfectant.
The duration of immunity is generally long‑lived, with UK vaccines being licensed with a three-yearly interval.
In the UK, pet ferrets are frequently vaccinated against distemper. Recent cases have been documented in litters brought into the UK from eastern Europe, so vigilance for distemper is still required.
Canine parvovirus (CPV) is a significant worldwide pathogen and still the most common cause of viral enteritis in dogs in the UK.
Since the virus was first discovered in 1978, it has evolved – and three known strains exist that can cause enteritis: CPV-2a, CPV-2b and CPV-2c.
In experimentally infected dogs, mortality without treatment is as high as 91%.
Although no definitive treatment has been reported, survival rates with intensive therapy can be up to 90%, while survival rates in tertiary, referral hospitals have been shown to be higher than those in first‑opinion practice.
Parvoviruses are small, non‑enveloped, single‑stranded DNA viruses. CPV emerged as a clinical problem in 1978 and it is thought to have arisen as a mutation of the feline panleukopenia virus.
Infection mainly occurs via the orofaecal route; rare transplacental infection is also reported. After infection, viral replication occurs within lymphoid tissue, spreading quickly to rapidly dividing cells.
Most infections are subclinical, with most older puppies and adult dogs undergoing seroconversion without evidence of clinical disease. Puppies with severe infections are usually younger than 12 weeks of age at the time of infection.
The virus replicates within intestinal crypt epithelium, bone marrow and myocardium. Animals initially become febrile and lethargic, with anorexia, vomiting and diarrhoea generally following two or three days later. Viral destruction of intestinal crypts results in villous collapse, intestinal bleeding and subsequent bacterial invasion, especially with enteric Gram‑negative bacteria.
Large volumes of foul‑smelling and bloody diarrhoea are commonly seen, and patients are often severely dehydrated on presentation. Intestinal protein loss may occur secondary to inflammation, causing hypoalbuminaemia. Damage to bone marrow progenitors can lead to neutropenia, furthering increasing the risk of intestinal translocation and serious bacterial infection.
Puppies that are infected in utero or younger than eight weeks of age may develop myocarditis due to damage as a result of viral replication in the myocardium.
Modified live CPV vaccines are available in the UK and based on CPV type two or CPV-2b subtypes. Several studies have shown vaccines containing CPV-2 confer adequate short‑term immunity against all CPV-2b and CPV-2c subtypes; however, no studies exist to show long‑term protection against these subtypes.
The current vaccination recommendations for CPV from the WSAVA are for initial vaccination at 8 to 9 weeks of age, followed by a second vaccination three to four weeks later and a third vaccination given between 14 to 16 weeks of age. All dogs should receive a booster 12 months after the completion of the primary vaccination course. Thereafter, recommendations for revaccination range from one to four years.
Infection with CPV confers lifelong immunity in the majority of cases. The duration of immunity is generally shorter, but can quite durable. In a study of 144 pet dogs from the UK that had not been vaccinated for periods of 3 to 15 years, 95% had protective CPV titres. Non‑vaccinated dogs are at highest risk of infection with CPV, although vaccinated puppies are frequently infected.
The clinical signs of CPV enteritis depend on the size of the inoculum, the age of the pup, the host’s defences and the presence of other enteric pathogens.
Maternally derived antibodies to CPV are protective during the first several weeks of life. The amount of antibody available in colostrum depends on the immune status and disease history of the mother, and the amount absorbed varies between individuals in the litter according to how much colostrum is taken in.
Maternally derived antibodies have a half-life of 10 days and puppies have a titre that is 50% of the dam. Therefore, a window of susceptibility to CPV infection exists between six weeks and six months of age, when declining maternal antibody levels interfere with a vaccine-induced humeral response, but cannot protect against infection.
Rottweilers, Dobermanns and Staffordshire bull terriers have been found to be at increased risk of CPV infection. This is thought to be due to a poor humoral response to vaccination in these breeds and persistence of maternal antibody past the age at which the primary vaccination course would normally be completed.
Intact male dogs are infected disproportionately to their population. Climate may also be a risk factor, with an increase in cases reported between the months of July and September in temperate climates.
Diagnosis of CPV infection can often be tentatively made on history and clinical findings. Leukopenia is commonly associated with parvoviral infection. Lymphocytosis is usually the direct result of viral replication at the time of initial infection and lymphocyte numbers usually rapidly rebound.
Profound neutropenia typically develops at the onset of gastrointestinal signs as a result of peripheral neutrophil consumption – especially in the gastrointestinal tract – and destruction of progenitor cells in bone marrow.
Although neutropenia is very suggestive of CPV enteritis, salmonellosis – or any other overwhelming infection – can cause similar haematological findings.
Parvoviral ELISA antigen SNAP tests are readily available in-practice tests to detect CPV in the faeces of infected dogs. The specificity of these tests is excellent – one study found the percentage of positive in-house tests was 80.4%, 78% and 77% for CPV‑2a, CPV‑2b and CPV‑2c, respectively – confirming the ability of the tests to detect the strains of the virus present in the UK.
ELISA results may be negative if the assay is performed early in the disease course as viral shedding is low at this stage, and tests should be repeated in dogs that show signs and maintain a clinical suspicion of CPV enteritis.
Vaccination with a modified live CPV vaccine may cause a weak positive result for 5 to 15 days post-vaccination. The period of shedding in clinical cases is relatively short and may be undetectable 10 to 14 days after infection.
If a clinical suspicion of CPV remains in a patient testing negative on the in-house tests, negative results should be confirmed by PCR-based methods. PCR tests have higher sensitivities and specificities than conventional methods of viral antigen determination in faeces. The high sensitivity of real-time PCR allows for identification of dogs shedding low titres of CPV in their faeces.
Treatment of parvoviral enteritis is primarily symptomatic and supportive. Fluid and electrolyte therapy is crucial to treat signs of vasodilatory shock, combined with antimicrobial therapy to treat signs of secondary bacterial sepsis.
Any patient being treated for CPV should be barrier nursed to prevent spread of infection within the hospital. The virus can persist in the environment for many months to years, so careful cleaning of the environment is essential. CPV is very sensitive to hypochlorite solutions and steam cleaning.
Canine infectious hepatitis (ICH) – or Rubarth’s disease – is rarely seen due to vaccination, although it is still occasionally seen in rescue centres in the UK.
ICH is caused by canine adenovirus 1 (CAV-1); this is closely related to CAV-2, which is part of the kennel cough complex (see later).
CAV-1 is very stable and can remain infective for up to 10 days in an environment absent of excessive dehydration. It is present worldwide and can affect most Canidae, including dogs, foxes, raccoons, bears and guinea pigs. Young animals are most susceptible to the disease and no strain variation has been identified.
As an immune response develops, immune complexes can form, causing a transient glomerulonephritis with increased urea and proteinuria. Subsequently, a focal interstitial nephritis can develop associated with virus particles within the tubule, which may account for the prolonged renal shedding that is sometimes seen.
Immune complexes are also the cause of the “blue eye” phenomenon that appears to be caused by interaction of the CAV-1 antigen in the corneal endothelium with antibody in the aqueous humour damaging the cornea (Figure 1). This rarely causes a problem and resolves over the course of 10 to 14 days.
Occasionally, more widespread ocular inflammation can occur, leading to anterior uveitis. The immune response usually results in high levels of neutralising antibodies that persist for many years.
Mild clinical signs may go unnoticed, or be associated with mild malaise or diagnosed at the point of development of blue eye.
Acute disease is usually associated with severe depression, anorexia, polyuria/polydipsia and in peracute cases death with no prior clinical signs. Less acute cases may then develop vomiting, abdominal pain, hepatomegaly, diarrhoea, haemorrhage, pallor and jaundice. CNS signs may develop due to bleeding within the brain. The prognosis for severe cases is poor.
Clinical signs of pallor, pyrexia and abdominal pain – with or without jaundice – are suggestive of CAV-1. Haematology and biochemistry findings are often inconclusive. Virus isolation from blood urine or liver biopsy may be possible.
In the recovering animal, a fourfold increase in antibody titre in an animal that has not recently been vaccinated is diagnostic. PCR can find evidence of viral antigen; however, the sensitivity and specificity of this test is not well understood due to the rarity of the disease.
Postmortem examination may reveal a typical picture of hepatitis, lymphadenitis and perivascular haemorrhage with intranuclear inclusions on histopathology, particularly within the liver. Immunofluorescent liver or kidney staining may document the presence of the antigen.
Treatment is mainly symptomatic and supportive with IV fluids, possible blood transfusion, antibiotics and intensive nursing.
Initial vaccines live‑attenuated strains of CAV-1; however, the occurrence of blue eye post‑vaccination – especially in Afghan hounds – led to a preference for killed vaccines and the development of live CAV-2 vaccines, which provide good cross‑protection to CAV-1.
All commercially available ICH vaccines in the UK are now live CAV-2 vaccines, which have the advantage that unlike CAV-1, CAV-2 has no trophism for the eye and, therefore, does not cause blue eye unless a pre-existing ocular pathology is present. In addition, an advantage exists of protection against the potential respiratory effects of CAV‑2.
In the UK, vaccination may be started as early as 6 weeks of age and is completed by 10 to 12 weeks, with three-yearly booster inoculations.
