Jane E. Sykes, BVSc(Hons), PhD, DACVIM
School of Veterinary Medicine, University of California-Davis, Davis, CA, USA
Influenza viruses are enveloped viruses with segmented single-stranded RNA genomes that belong to the family Orthomyxoviridae. Influenza viruses that cause disease in domestic animals belong to the genus Influenzavirus A. Influenza B and influenza C viruses circulate mostly among humans. Influenza A viruses are classified based on the composition of their hemagglutinin (H) and neuraminidase (N) genes. To date, 18 H types and 11 N types have been identified, each of which are antigenically distinct. Genomic rearrangements that occur within influenza A viruses allow for occasional cross-species transmission. These occur when two different viruses simultaneously infect a host, with subsequent genetic reassortment. Occasionally, cross-species transmission occurs without alteration of the viral genome. The names of influenza viruses are specified as follows: influenza genus (A, B or C)/host/geographic origin/strain number/year of isolation and, in parentheses, H and N type. For example, A/canine/Florida/43/2004 (H3N8).
In the USA, canine influenza virus (CIV) emerged in racing greyhounds in Florida in 2003 and 2004,1 where it caused hemorrhagic pneumonia and a high mortality. Serological evidence of infection in the greyhound dog population dates back to 1999.2 Infections spread slowly and have subsequently been reported in racing greyhounds and non-greyhounds in at least 38 US states. Outbreaks have continued to occur in shelter situations for nearly a decade after the virus was discovered. The virus that has circulated in the USA is an H3N8 virus that resembles an equine influenza virus, which suggested that an interspecies jump occurred without genetic reassortment.1 Instead, accumulation of point mutations with minor amino acid changes occurred, followed by sustained transmission among dogs. The most significant outbreaks of disease due to CIV have occurred in Florida, New England, Colorado, Wyoming, and Texas. In other states, sustained transmission of the virus from one dog to another has not occurred. The most significant risk factor for infection has been indoor housing.3 Virtually all cases to date have involved dogs in kennels, animal shelters, or dog daycare facilities. Dogs of all ages and breeds are susceptible, but to date severe hemorrhagic pneumonia has only occurred in greyhounds. The virus is shed for up to 7 to 10 days, but is typically shed for just a few days. In some dogs, shedding may have ceased when clinical signs are most apparent. Canine influenza virus can still infect horses, but horses develop only mild disease or no clinical signs.
Although infections with influenza viruses may be more likely to produce signs of fever and lethargy than dogs infected with other respiratory pathogens (e.g., Bordetella bronchiseptica, canine respiratory coronavirus, canine distemper virus, canine herpesvirus, canine adenovirus 2, canine parainfluenza virus), it is not possible to diagnose influenza virus infections in dogs based on clinical signs alone. The high prevalence of coinfections and increased severity of disease when multiple pathogens are present further complicate diagnosis. A history of exposure to other animals with respiratory disease can raise suspicion for the diagnosis.
When outbreaks occur, attempts to make a diagnosis are indicated. Collection of multiple specimen types (oropharyngeal swabs, nasal swabs, and, if possible, transtracheal or bronchoalveolar lavage specimens) from several dogs with and without clinical signs can facilitate diagnosis and allow interpretation of the significance of positive test results. Organism detection methods, such as PCR, are likely to be of highest yield early in the course of illness (e.g., the first 1 to 3 days), or in exposed dogs that have not yet developed clinical signs. Using a combination of serology and organism detection methods (culture or PCR) may also facilitate diagnosis. Necropsies can provide valuable information and should be performed as soon as possible after death or euthanasia occurs by a veterinary pathologist. Tissues should be submitted for histopathology (in formalin), bacterial and virus cultures (fresh tissue), and/or PCR for respiratory viruses and bacteria. Despite the increased availability of molecular diagnostic assays, virus isolation is still offered to veterinarians for routine diagnostic purposes by some veterinary diagnostic laboratories that specialize in virology (e.g., the Animal Health Diagnostic Laboratory at Cornell University in the USA).
Panels of real-time PCR assays that detect respiratory pathogens may include assays for CIV. Unfortunately, false-negative PCR results are common because of transient or low-level shedding of many respiratory viruses. In addition, because influenza viruses are RNA viruses, false negatives may result from degradation of viral RNA during specimen transport.
Point-of-care assays are available for detection of nucleoprotein antigen to human influenza A viruses. Unfortunately, such assays have limited sensitivity and specificity for diagnosis of CIV infections.
Serological assays for CIV exposure are based on serum neutralization or hemagglutination-inhibition. Serology is of limited use for diagnosis because of vaccine titer interference in regions where vaccination is performed, and the high prevalence of subclinical exposure in regions where infection is endemic. Titers may be negative in the first 10 days of illness. Despite these limitations, serological assays have been key to identification of outbreaks of disease caused by CIV, when the disease is not endemic and widespread immunization has not yet been performed. Analysis of paired serum specimens collected 2 weeks apart can be used to document recent infection. In some dogs, no other diagnostic test may be useful for antemortem diagnosis because virus shedding is so transient and difficult to detect. Assays for CIV that use equine influenza virus antigen for antibody detection have suboptimal sensitivity.9
Treatment and Prevention
Treatment of influenza virus infections is supportive. The efficacy and optimal dosage of neuraminidase inhibitors like oseltamivir is unknown, and because oseltamivir is a first-line treatment for pandemic influenza in humans, it should not be used to treat dogs with respiratory disease, even when CIV infection is known to be present. In the United States, inactivated, parenteral vaccines are available for reduction of disease caused by H3N8 CIV and viral shedding. Their use has been recommended for dogs that may contact other dogs in regions where CIV is endemic. Vaccination against CIV is also required for importation of North American dogs to Australia. The initial vaccine may be given as early as 6 weeks of age. Because CIV vaccines are inactivated, 2 initial doses are required 3 to 4 weeks apart, and maximum immunity does not occur until 1 week after the second dose. As a result, CIV vaccines may not protect dogs that enter shelters with endemic canine influenza.
Public Health Significance
There is currently no evidence of zoonotic transmission of CIV. However, a recent study revealed that a variety of human influenza viruses can infect the canine trachea, and that reassortment of these viruses with CIV results in viable viruses.10 Thus dogs have the potential to be sources of novel viruses that could lead to influenza virus pandemics in humans.
Other Influenza Virus Infections
Avian-lineage H3N2 CIV emerged in South Korean dogs in 2007, and a similar virus was subsequently isolated from dogs in China.4 Experimental evidence exists that cats may also be susceptible to infection by this virus. A novel H3N1 virus was also detected in South Korean dogs that lacked clinical signs of respiratory disease.5 A novel H5N2 influenza virus was detected in a dog with respiratory disease in China and was shown to be transmissible to other dogs, cats and chickens.6 Dogs are susceptible to infection with human influenza virus H1N1, avian H5N1, and avian H6N1, but sustained transmission of these viruses in the dog population has not been reported. Serologic evidence of exposure of feral dogs in China to avian influenza virus H10N8 has been reported. Limited infection of dogs with equine H3N8 viruses was detected in hounds in England7 and during an equine influenza outbreak in Australia. In England, disease was so severe that several hounds had to be euthanized, and subacute bronchointerstitial pneumonia was detected at necropsy. The Australian dogs developed inappetence, lethargy, nasal discharge, and a cough that persisted for several weeks, but dog-to-dog transmission was not identified. Experimental transmission of H3N8 influenza virus from horses to dogs was documented in Japan, but the infected dogs did not show clinical signs of illness.8
1. Crawford PC, Dubovi EJ, Castleman WL, et al. Transmission of equine influenza virus to dogs. Science. 2005;310:482–485.
2. Anderson TC, Bromfield CR, Crawford PC, et al. Serological evidence of H3N8 canine influenza-like virus circulation in USA dogs prior to 2004. Vet J. 2012;191:312–316.
3. Barrell EA, Pecoraro HL, Torres-Henderson C, et al. Seroprevalence and risk factors for canine H3N8 influenza virus exposure in household dogs in Colorado. J Vet Intern Med. 2010;24:1524–1527.
4. Lin Y, Zhao Y, Zeng X, et al. Genetic and pathobiologic characterization of H3N2 canine influenza viruses isolated in the Jiangsu Province of China in 2009–2010. Vet Microbiol. 2012;158(3–4):247–258.
5. Song D, Moon HJ, An DJ, et al. A novel reassortant canine H3N1 influenza virus between pandemic H1N1 and canine H3N2 influenza viruses in Korea. J Gen Virol. 2012;93:551–554.
6. Hai-xia F, Yuan-yuan L, Qian-qian S, et al. Interspecies transmission of canine influenza virus H5N2 to cats and chickens by close contact with experimentally- infected dogs. Vet Microbiol. 2014;170(3–4):414–417.
7. Daly JM, Blunden AS, Macrae S, et al. Transmission of equine influenza virus to English foxhounds. Emerg Infect Dis. 2008;14:461–464.
8. Yamanaka T, Nemoto M, Tsujimura K, et al. Interspecies transmission of equine influenza virus (H3N8) to dogs by close contact with experimentally infected horses. Vet Microbiol. 2009;139:351–355.
9. Anderson TC, Crawford PC, Katz JM, et al. Diagnostic performance of the canine influenza A virus subtype H3N8 hemagglutination inhibition assay. J Vet Diagn Invest. 2012;24:499–508.
10. Gonzales G, Marshall JF, Morrell J, et al. Infection and pathogenesis of canine, equine and human influenza viruses in canine tracheas. J Virol. 2014; Epub ahead of print].