Update on canine and feline influenza (Proceedings)

Influenza A viruses are divided into subtypes according to the serological reactivity of the surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). There are 16 HA (H1–H16) and 9 NA (N1–N9) subtypes (the current bird flu is H5N1). All surface glycoproteins HA and NA can be isolated from aquatic birds, the reservoir for influenza A viruses. In mammals, there is partial restriction of the host range with few subtypes of viruses being able to infect a particular host. Humans can harbor H1, H2, H3 with N1 or N2. Horses have two main types, H7N7 lastly reported in the 1980's and the H3 N8. The horse influenza vaccine has the H3N8 type virus.

The influenza virus is highly prone to antigen drift making vaccine development challenging. Interspecies transmission can occur by gene reassortment or direct transfer of the unaltered virus. Either form of transmission is rare and usually a dead-end event [1]. Some form of interaction between the different hosts is necessary for inter-species transmission. In addition, the novel host should possess the appropriate viral receptors in the respiratory tract to enable the virus to bind to the respiratory epithelial cells. The virus also must be able to replicate efficiently within the cells of the new host and be sufficiently virulent if it is to have the capacity to transmit secondarily to new susceptible contacts [1]. The 1968 H3N2 human flu pandemics resulted from a bird virus that suffered gene reassortment, acquire the ability to infect people and be transmitted from person to person. The current H5N1 bird flu has caused disease in people, but the virus is poorly adapted to humans. Horizontal transmission has been rare and it is usually nonsustained [2]. In the few suspected cases [3], close physical contact, for example between mother and child without the use of precautions such as gloves, nose-mouth masks, or antiviral treatment, was responsible. Experimentally, the H5N1 virus can be transmitted to ferrets, mice, pigs and cats.

The H5N1 Bird Flu and Cats

Cats may be more than collateral damage in the H5N1 influenza global spread and may play a role in the epidemiology of the virus [4]. The WHO reported the first outbreak of H5N1 virus in cats [5] in February 2004. Fourteen of 15 cats in a household in Thailand, became weak, started vomiting and coughed up blood before dying. One of the cats ate a chicken carcass on a farm where there was an H5N1 virus outbreak. The presence of H5N1 virus was confirmed in three of the cats [6]. The 2004 outbreak in domestic cats was similar to an incident that occurred three months previously at a zoo in Thailand, during a local outbreak of H5N1 influenza. At this zoo, two tigers and two leopards died suddenly after feeding on fresh chicken carcasses. The cause of death was severe pneumonia probably due to H5N1 virus infection [7]. Also in 2004, there was a second outbreak of H5N1 virus infection at another zoo in Thailand, again involving consumption of virus-infected chicken. This time, a total of 147 tigers died or were killed [8]. Before these reports, both domestic cats and wild felids were considered to be resistant to disease from influenza A virus infection [6]. H5N1 infection has also been reported in a cat infected by eating a pigeon carcass. The virus isolated from the pigeon and the cat showed the same cluster as the viruses obtained during the outbreak in Thailand [9].

Cats become sick when inoculated with the H5N1 virus. Eight cats experimentally-infected with H5N1 virus [4, 10] intra-tracheally (three), by feeding on virus-infected chicks (three), or through close contact between infected and non-infected cats (two) excreted virus from the pharynx, nose and rectum. Excretion lasted from three days post-infection until the end of the experiment on day seven, when the cats were killed. The amount of excreted virus recorded from cats was much lower than the levels excreted by chickens. Clinical signs were observed several days earlier in cats infected by direct respiratory and oral routes, than by cat-to-cat transmission. The signs included fever, lethargy, conjunctivitis, and labored breathing. In some cats, virus excretion started before clinical signs were noted. Post-mortem examination demonstrated multiplication of the virus not only in the respiratory tract [4], but also in a number of other organs [10]. The presence of virus in most tissues was associated with cell death and inflammation. Viral infection in the nervous tissues of the intestinal wall was found only in cats fed on virus-infected chicks. This suggests that the virus reached these tissues directly from the guts — a novel route of entry for influenza virus in mammals. The H5N1 virus attaches abundantly to the cells lining the lungs of cats, but not to those in upper parts of the respiratory tract [11], similar to what happens in the respiratory tract of persons infected with H5N1 virus.

We may just be learning what is already common knowledge among Indonesian villagers. Poultry keepers have an onomatopoeic name for bird flu in the local Javanese dialect "that sounds like 'plop', the sound of a chicken hitting the ground when it falls out of a tree. They also have a name for the cat form of avian flu — 'aaargh plop' — because cats make a screaming noise before they fall out of the tree." [5] There were widespread and high mortality of cats in cats in Iraq during an outbreak of H5N1 virus in poultry, whereas dead or moribund cats were found to be infected with H5N1 virus soon after the virus was detected in wild birds in Germany [6]. Apart from the role that cats may potentially play in H5N1 virus transmission to other species, they also may be involved in helping the virus to adapt to a more efficient human-to-human transmission [4]. In an outbreak of H5N1 virus, cats may get the virus from ingestion of contaminated chicken. Once infected they may spread the virus to other cats, between poultry farms and also bring the virus close to people.[12]

The European Standing Committee on the Food Chain and Animal Health (SCFCAH) has issued precautionary recommendations for companion animal owners and veterinarians in areas where H5 N1avian influenza has been confirmed in wild birds [13]. The SCFCAH recommends that: 1) Sick or dead cats and dogs that may have had contact with infected wild birds or their carcasses should undergo veterinary inspection or postmortem examination. When felt necessary by the veterinarian, and in accordance with instructions given by the veterinary authorities, further testing should be carried out. 2) Contact between domestic carnivores, particularly cats, and wild birds should be prevented; cats should be kept indoors and dogs should be kept on a leash or otherwise restrained, and kept under control by the owner. 3) Where stray cats or dogs are found dead, they should not be touched, and the veterinary authorities should be informed, so that postmortem examination and further testing can be performed.

The H5N1 Bird Flu and Dogs

In an 2005 unpublished study by the National Institute of Animal Health in Bangkok, 160 of 629 village dogs in central Thailand had antibodies against H5N1, indicating that they were infected with the virus or had been infected in the past. The virus has been isolated from at least one of the dogs [14]. However, there is no evidence that dogs become ill or are able to spread the H5N1 virus.

The H3N8 Canine Influenza Outbreak

The current canine outbreak is a direct transfer of an unaltered virus (H3N8) from horses [15]. Sequencing of HA and NA genes showed a 96 - 98% homology with a recent H3N8 equine influenza virus [16]. Influenza has been sporadically identified in dogs previously, but this is the first time in which dog-to-dog transmission has easily occurred. The canine outbreak was first detected on January 2004 in racing Greyhounds in Florida [15]. It is not clear what association the greyhounds had with horses; the virus may have initially been transmitted from infected horses via the usual route of aerosol transmission, or alternatively it might be through consumption of untreated meat, including lungs, from an infected horse. [1] The canine H3N8 has now spread to animal shelters and the pet population. The Cornell University Animal Health Diagnostic Center has identified anti-influenza antibodies in dogs not affiliated with Greyhound racetracks from several states and the District of Columbia. A clinical syndrome compatible with canine influenza has also been observed in Mexico.

The equine H3N8 virus has been around for 40 years and is unlikely to affect people due to the restriction imposed by the relative lack of α2,3 sialic acid linkages on human tracheal epithelial cells. There has been no real evidence of disease occurring in horse owners or trainers during outbreaks of equine influenza in horses [1]. Equine HA (like avian HA) specifically recognizes α2,3 sialic acid linkages in receptors on the surface of equine tracheal cells, whereas the human influenza HA recognizes the α2,6 sialic acid linkages that predominate on the surface of human tracheal epithelium [18]. However, the lack of the relevant receptor is not a complete barrier to cross-species transmission of influenza, as evidenced by the recent infections of people with avian H5N1 viruses.

Since Canine Influenza still a new disease, most dogs are susceptible. The incubation period is 2 – 5 days and animals may shed the virus for 10 days after development of clinical signs [19]. In a naïve population, infection rates may approach 100%, with 80% of the dogs developing clinical signs. This helps to differentiate influenza from kennel cough in a kennel setting. Mortality approached 5% in high risk populations, but it is likely < 1% otherwise [20]. Clinical signs are similar to the ones observed in kennel cough, with the majority of dogs showing a mild form with light fever, cough (moist or dry, soft or loud) for 10 – 21 days and purulent nasal discharge. As with other tracheobronchitis, the clinical signs are generally mild, the disease resolves without treatment, and treatment does not noticeably alter the course or duration of the disease [20]. Dogs with severe form have high fever and clinical signs of hemorrhagic pneumonia. Death may occur as early as 4 hour after the onset of clinical signs [19]. Secondary bacterial pneumonia is common with Streptococcus equi subsp. zooepidermicus being isolated in all for dogs in one study [16].

The most reliable way to diagnose canine influenza is detection of antibodies against the Influenza virus. Acute and convalescent serum samples should be collected, but a single serum sample may be used in dogs that have recovered from a respiratory infection. This will document previous exposure to canine influenza. Nasal swabs can be used for viral detection through PCR. Viral isolation is unreliable at present [20].

Management of the uncomplicated cases is similar to the management of Kennel cough. Treatment of the severe form is supportive with fluids and antibiotics [19]. Dogs with greenish mucopurulent nasal discharge may have secondary nasal bacterial infection that usually does not respond well to doxycycline, quinolones or clavamox. However, first generation cephalosporins cause improvement within 3 days [21]. Pneumonia should be treated aggressively with four quadrant antibiotic therapy. Antiviral therapy has not been adequately tested in naturally-occurring influenza in dogs. Neuranimidase inhibitors (oseltamivir or tamiflu) have been used empirically because Type A virus express neuraminidase [20]. The canine influenza also is sensitive in vitro to amantidine. All dogs with respiratory infections should be isolated using protocols in place for kennel cough. Clothes, hands, equipments and surfaces should be cleaned after exposure. Fortunately, the influenza virus is sensitive to most disinfectants. There is no vaccine for canine influenza yet, but dogs should be vaccinated against other respiratory agents. This will decrease false alarms and allow the ruling-out of the agents present in the vaccine when facing a sick dog.

References

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17. Cornell University Animal Health Diagnostic Center, Test Summary for Canine Influenza Virus in Dogs not Affiliated with Greyhound Racetracks. 2006. http://www.diaglab.vet.cornell.edu/issues/civ-stat.asp

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19. Center of Disease Control, Media Briefing on Canine Influenza. 2005, CDC. http://www.cdc.gov/od/oc/media/transcripts/t050926.htm

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21. Crawford, P.C. personal communication. 2006.