Emerging viral pathogens (Proceedings)

Canine Influenza

An outbreak of respiratory disease occurred in a kennel of racing greyhounds in 2004. While some dogs exhibited mild disease with fever and cough, some experienced peracute death with pulmonary hemorrhage (case fatality 36%). Virologic analysis revealed an influenza virus that was later found to be closely related to equine influenza virus subtype H3N8, sharing >96% genetic sequence identity. Retrospective studies on archival sera indicated infection had occurred in dogs as early as 2000. Additional outbreaks of respiratory disease have been associated with canine influenza since its identification.

Fortunately, most cases are mild, resembling kennel cough with a course of 14-21 days. Some manifest more severe disease with high fever and purulent nasal discharge; secondary bacterial infections are a major concern. Mortality rates of 1-10% have been reported, and are highest in puppies, elderly animals, and animals with concurrent disease.

Sustained transmission is occurring in dogs, and infection has been documented throughout the US. Racetracks, kennels, and other environments where dogs are housed together appear to be at greatest risk. As all dogs are susceptible and the virus appears to be quite contagious, continued spread is likely; aerosol as well as fomite transmission may occur.

Diagnosis is by serological analysis and virus identification by antigen detection, virus isolation, or PCR. Virus detection must be done early in the disease process. Supportive care including antibiotics appears to be very beneficial. Antiviral treatment using human medications such as Tamiflu have been done, but clinical studies have not yet been published. Currently, no vaccine is available for dogs; the equine vaccine should not be used in dogs.

Canine Respiratory Coronavirus

In 2003, an investigation into endemic respiratory disease in a large kenneled dog population in the UK identified a canine coronavirus distinct from the enteric canine coronavirus. The virus, a group 2 coronavirus closely related to bovine coronavirus, was found in tracheal washes and lung tissues, indicating infection of both upper and lower respiratory tracts. Subsequent studies showed significant prevalence in continental Europe and North America in addition to the UK. This pathogen must be considered in cases of respiratory disease in well-vaccinated dogs. Current diagnostics rely on serology (be sure to request canine RESPIRATORY coronavirus!) and virus identification by antigen detection, virus isolation, or PCR.

Canine Distemper

Canine distemper continues to be an important pathogen of dogs. The advent of vaccination for CDV in the 1950s led to a decrease in the incidence of distemper in dogs. However, infection with and outbreaks involving canine distemper virus (CDV) still occur. As with other RNA viruses, strains of CDV have genetic variability. Genetic characterization of CDV isolates has identified six major genetic lineages: America-1 and -2, Asia-1 and -2, European, and Arctic. Many commercial vaccines utilize strains from the America-1 lineage (Snyder Hill, Onderstepoort, Lederle) though these genotypes do not appear to be circulating in the field currently.

Novel CDV strains have been identified in recent years throughout the world. Oubreaks involving strains that appear to be derived from distant geographic locales have been documented. For example, the Arctic lineage has been found in Italy and isolates from dogs in Hungary have been found to resemble those from North America, likely due to extensive and often uncontrolled movement and trade of dogs. Distinct isolates have also been detected in North America. In 2004, phylogenetic analysis of virus from four clinical cases in the US identified three strains genetically distant from strains previously identified in North America. The dogs in three of these four cases had recently been vaccinated. Genetic characterization of the viruses from these cases found they were novel for the continental US. Outbreaks among raccoons in the Chicago area in 1998 and 2001 were also due to genetically distant lineages; in addition, the 2001 variant appeared to be more lethal. An investigation of North American isolates in 2007 identified genotypes distinct from vaccinal strains. Circulation in wildlife populations may lead to virus variants of antigenicity as well as virulence.

Contact with wildlife may result in CDV transmission to domestic dogs. An outbreak of CD in Alaska led to the death of several hundred dogs. The virus was isolated and characterized, and was found to be most closely related to a Phocine Distemper virus from an outbreak among Baikul Seals in Siberia. In the USA, significant seroprevalence has been found in raccoons in periurban regions. These raccoons are believed to have transmitted the virus to captive felids in an urban zoo, and may have been the origin of virus in a Chicago area outbreak among domestic dogs.

Genetic diversity has been associated with vaccine failures. As new strains of CDV continue to emerge, surveillance and characterization of isolates from field cases will be necessary. Antigenic, pathogenic, and genotypic descriptions of new isolates will provide important information about this important pathogen required to maintain safe and efficacious vaccines.

Canine Parvovirus-2c

Since its emergence, canine parvovirus (CPV) has continued to evolve. The virus, a single-stranded DNA virus, has a significant mutation rate that more closely approaches that of RNA viruses. This has led to amino acid changes in the capsid protein that alter antigenicity, though current variants are closely related. Canine parvovirus 2a and 2b have replaced the original emergent virus, CPV-2. In recent years, additional mutations have been noted in some circulating isolates. While these newer variants differ in only a few amino acid residues from the more prevalent CPV-2b, they can be distinguished with monoclonal antibodies as well as genetic sequencing. These isolates vary in which specific amino acid residue changes have occurred, but at least 3 have been given CPV-2c designations, making the nomenclature confusing.

A CPV variant that has a mutation at amino acid residue 426, an important antigenic epitope of CPV, from aspartic to glutamic acid in the capsid protein has emerged. This isolate was originally identified in Italy but has since been identified throughout the US. Current vaccines appear to be protective against the new variant. However, it is not known whether ELISA detection kits, which use monoclonal antibodies (specific for a single epitope) for virus detection are equally effective with this newer variant; this is being investigated. The disease syndrome associated with the Asp426Glu mutant appears to be similar to that of previous variants, with mucoid to hemorrhagic diarrhea and lymphopenia.

Virulent Systemic Calicivirus

In 2000, an isolated epizootic of a virulent systemic disease (VSD) attributed to feline calicivirus (FCV) was described by Pedersen and others. Since then, additional outbreaks in the US and UK have been described. The symptoms have included a high fever, oral ulcers, subcutaneous edema, and ulcerative dermatitis. Interstitial pneumonia, as well as hepatic, splenic and pancreatic necrosis have also been described. The disease has a significant mortality, even in vaccinated cats.

Mutations in the viral genome are believed to be responsible for the change in phenotype of the virus, but each variant from the different outbreaks have been distinct. In fact, no consistent genetic motif has been associated with this disease manifestation. Most have arisen from a shelter or rescue facility, and have "burned out" almost as quickly as they started. This last fact is likely due to the lack of subclinical infection, and the strict quarantine and other control measures implemented in these outbreaks. Host and immune factors are also speculated to play a role in this disease syndrome. Alterations in certain cytokines have been found in affected tissues, suggesting an immunopathogenicity.

Diagnosis of VSD associated with calicivirus involves clinical signs, history, identification of calicivirus in lesions (e.g. swabs of oral ulcers, blood, epidermal biopsies), and elimination of other potential causes. As stated above, no specific viral assay for the FCV of VSD currently exists. At least one commercial vaccine has been released that contains two FCV strains, including one associated with VSD. Since antigenicity does not correlate with disease syndrome, inclusion of two or more strains isolated from different disease manifestations does not necessarily insure broad protection against the varied pathogenic phenotypes. Synergy with the combination of isolates must be demonstrated to substantiate claims of broad antigenic protection.

Avian Influenza

The emergence and spread of the H5N1 strains of avian influenza in recent years has caused concern over a future pandemic in the human population. The virus, a particularly virulent and contagious strain, has affected waterfowl and domestic poultry in Asia, Europe, the Middle East and Africa. In addition, it has successfully infected humans in contact with infected birds, leading to severe disease, and death in over 50% of cases. Thusfar, efficient human-to-human spread has not occurred.

Infection has also occurred in domestic cats and dogs. Seropositive dogs and cats have been found in Thai villages. Natural infection of dogs has occurred from ingestion of infected carcasses. In some cases, systemic disease and death have occurred. Cats also may be infected by consumption of carcasses of infected birds. During an outbreak in Germany among waterfowl, infection of several domestic cats occurred. Infections were fatal, and pneumonia and hepatic necrosis was found. Experimental studies in cats have produced lethal infections, and spread to in-contact cats. Shedding was documented in both respiratory secretions and feces of infected cats. Inoculation studies in dogs have shown susceptibility of dogs to infection with H5N1, and shedding may occur from the nose with no signs of disease. This study also showed receptors for the avian influenza exist in both the upper and lower respiratory tracts of dogs.

Because these animals live in close contact with humans, concern exists over the risk of transmission from these animals. This possibility also brings questions from owners regarding risks to their pets, and themselves. Currently, it is unlikely that cats and dogs play any role in the natural transmission of avian influenza. No direct transmission has been reported, and the level of shedding by these animals appears to be lower than that of birds. However, monitoring of domestic pets during an H5N1 outbreak is warranted.

Rabies

Rabies virus continues to be a threat to domestic pets worldwide. Recently, it was announced by the CDC that the canine strain of rabies has been eliminated from the US. However, the virus remains present in wildlife in the US, posing a risk for domestic pets, as well as people. Lyssaviruses continue to emerge in other parts of the world, and genetic variants of rabies virus do exist. New variants of rabies virus in North America could occur and pose an emerging threat. Rabies infections in raccoons are of particular concern due to the increased likelihood of raccoon contact with pets as well as people in suburban areas. In addition, importation of dogs poses a risk for introduction of foreign variants. Data indicates an increasing number of unvaccinated puppies are being imported into the US, and since 2004, infection has been documented in at least two imported puppies. Federal regulations are under review to address these risks.

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