Avian influenza: An emerging feline threat? (Update)

Article

Historically, cats have been considered to be resistant to influenza virus infections.

Margaret C. Barr, DVM, PhD

College of Veterinary Medicine

Western University of Health Sciences

Pomona, CA 91766

Editors' note: This is an excerpt of a peer-reviewed article that originally ran in Veterinary Medicine's October 2005 issue. It has been updated to include information about the continued spread of avian influenza in cats.

HISTORICALLY, cats have been considered to be resistant to influenza virus infections. Cats can be experimentally infected with human H3N2 virus, but the infection is usually subclinical.1 Although cats live in close contact with people, feline influenza outbreaks have not been recognized. Whether human-to-cat transmission is possible is unknown, but it clearly has not been associated with disease in the past. However, we now know that cats can—and do—become infected with the H5N1 strain of avian influenza virus.

Reported cases in nondomestic and domestic cats

In December 2003, two tigers and two leopards in a zoo in Thailand died after exhibiting signs of fever and respiratory distress.2 The animals had been fed fresh poultry carcasses from a local slaughterhouse. Although the diagnosis had not been made at the time, chickens in the area were dying of H5N1 influenza virus infections. Postmortem examination of tissues from the tigers and leopards revealed fibrinous pneumonia, multifocal hemorrhage in internal organs, and encephalitis. Immunohistochemistry, reverse transcriptase-polymerase chain reaction testing, and virus isolation confirmed a diagnosis of H5N1 avian influenza virus infection. The virus was virtually identical to the strain that was circulating in chickens at the time of infection. All the animals had been vaccinated with an attenuated feline panleukopenia virus vaccine two weeks before their illness. Although there was no evidence of panleukopenia virus-induced disease, immunosuppression associated with the vaccine may have contributed to the severity of the influenza in these cats.2

Domestic cats in Thailand have also been infected with the H5N1 virus.3,4 In February 2004, a group of 15 cats living near an affected poultry farm became ill. According to news reports, three of the cats had been tested for avian influenza by researchers at Thailand's Kasetsart University, with two cats having positive results at that time. Fourteen of the 15 cats had died, and the last cat was very ill. The method of influenza transmission in these cats was unknown. During the same month, another cat in Thailand became ill five days after eating a pigeon carcass.5 The cat was initially febrile and depressed and then developed convulsions and ataxia before it died two days after the onset of illness. H5N1 influenza virus antigen was detected by immunohistochemistry in brain, heart, lung, liver, kidney, and spleen samples from this cat. Virus isolates from the cat were almost identical to isolates from infected pigeons and chickens in the same region.

A second outbreak of H5N1 avian influenza in nondomestic cats occurred in October 2004 in a tiger zoo in Thailand.6 Initially, the cats likely became infected by ingesting raw infected bird carcasses. Tigers infected later in the outbreak were probably infected by cat-to-cat transmission because they were fed cooked poultry beginning a few days after the first tigers became ill. Clinical signs in affected tigers included respiratory distress, a serosanguineous nasal discharge, neurologic signs, and high fever. Leukopenia, thrombocytopenia, and elevated liver enzyme activities were common laboratory findings. Most of the animals had severe lung congestion and hemorrhage. Infection with H5N1 avian influenza virus was confirmed in several animals by using immunohistochemistry, virus isolation, or both techniques. Twenty-nine tigers died during the first week of the outbreak, and a total of 147 of the zoo's 441 tigers either died or were euthanized during the three weeks after the first tigers became ill.

In February 2006, a domestic cat in Germany was infected with H5N1 avian influenza virus, probably by ingesting an infected wild bird. This case was quickly followed by the detection of three H5N1-positive cats in Austria.7 Several H5N1-infected swans were found in the same regions as the infected cats. In response, the European Standing Committee on the Food Chain and Animal Health (SCFCAH) issued recommendations for veterinarians and pet owners. The statement recommended inspecting and testing sick or dead cats that might have had contact with wild birds, reporting suspected cases to appropriate authorities, and preventing contact between pet cats and wild birds. It also recommended the same procedures for dogs. The SCFCAH report emphasized that the risk of avian influenza virus infections in cats remains low, and the risk of cat-to-human transmission is even lower at this time.8

Experimental inoculation of domestic cats

In addition to these outbreaks, researchers have demonstrated the susceptibility of domestic cats to H5N1 avian influenza virus.9 Unlike in previous studies with other influenza virus strains, cats developed severe respiratory disease after exposure to H5N1 virus by ingestion, intratracheal inoculation, or contact with experimentally infected cats. Intratracheal inoculation of three cats resulted in fever beginning Day 1 after exposure and in decreased activity, conjunctivitis, and labored breathing by Day 2 after exposure. One cat died on Day 6. Pathologic findings included focal pulmonary consolidation and diffuse alveolar damage. Two cats housed with these infected cats and three cats fed virus-infected chicks also developed similar clinical signs and pathology. Infection with H5N1 avian influenza virus was confirmed in all these cats by virus isolation from pharyngeal swabs and by immunohistochemistry on lung tissue.

Concerns over an H5N1 influenza pandemic

Although human cases have been sporadic to date and efficient human-to-human spread has not yet occurred, concerns about a potential H5N1 influenza pandemic continue to rise. For the first time since the current H5N1 influenza outbreak began in 2003, migratory birds appear to be spreading the highly pathogenic avian influenza virus to domestic birds in countries along their migratory routes. The virus has now been detected in birds in at least 32 countries.10 Despite this explosive spread in birds, little more than 200 human cases of H5N1 influenza have been confirmed during the current outbreak; most of these cases can be traced to direct contact with sick or dead birds or their feces.

However, fears of an avian influenza pandemic remain because of the ability of influenza viruses to mutate and change or expand their host range. Influenza viruses carry their genes on eight separate segments; infection of a single host cell with two different influenza viruses can result in a new virus strain by packaging segments from both parent viruses in a single virus particle (genetic reassortment). If such a reassortment resulted in enhanced transmission between people, a pandemic might occur.10

The veterinarian's role in influenza surveillance

The H5N1 influenza outbreaks in domestic and nondomestic cats point to this virus's potential as a feline pathogen. Although poultry and wild ducks are the virus's primary reservoir, several species of songbirds are also susceptible to infection.11 These bird populations could serve as a conduit of human infection through feline intermediaries. With each genetic reassortment of the influenza viruses, species barriers become less effective (Figure 1). It therefore seems reasonable for veterinarians to consider including influenza as a differential diagnosis in cats with respiratory and neurologic disease. Prompt recognition of avian influenza in any susceptible population of animals will help control its spread and decrease the chance of another devastating influenza pandemic.

1. Genetic reassortment of influenza viruses may lead to additional species being involved in transmission.

If you suspect avian influenza in any species, contact the Animal Health Diagnostic Center, College of Veterinary Medicine, Cornell University (phone: 607-253-3900; e-mail: diagcenter@cornell.edu) for testing information. Report cases of avian influenza to local or state public health departments or the county veterinarian.

Although guidelines for handling infected pets have not been established, human infection-control precautions recommended by the Centers for Disease Control and Prevention can be adapted for use in companion animals. Use stringent hygienic care (including using gloves, gowns, and masks) when handling potentially infected animals, and maintain these animals under isolation conditions until testing is completed or for 14 days after the onset of clinical signs.

Treatment of influenza virus infection in cats would probably be based on supportive care. Influenza antiviral agents have not been tested in cats, so their safety and efficacy are unknown. The use of antiviral drugs such as oseltamivir or zanamivir in nonhuman species is discouraged because of concerns that circulating strains of influenza might develop resistance to these drugs. In fact, the extralabel use of anti-influenza drugs in poultry has been banned by the FDA.12

REFERENCES

1. Hinshaw VS, Webster RG, Easterday BC, et al. Replication of avian influenza A viruses in mammals. Infect Immun 1981;34:354-361.

2. Keawcharoen J, Oraveerakul K, Kuiken T, et al. Avian influenza H5N1 in tigers and leopards. Emerg Infect Dis 2004;10:2189-2191. Available at: www.cdc.gov/ncidod/EID/vol10no12/04-0759.htm. Accessed May 23, 2006.

3. Care urged after bird flu infected feline found. China Daily. Available at: www2.chinadaily.com.cn/english/doc/2004-02/20/content_307975.htm. Accessed March 29, 2005.

4. The World Health Organization Communicable Disease Surveillance & Response (CSR). Avian influenza (H5N1)—update 28: reports of infection in domestic cats (Thailand), situation (human) in Thailand, situation (poultry) in Japan and China. 20 February 2004. Available at: www.who.int/csr/don/2004_02_20/en/. Accessed Sept. 15, 2005.

5. Songserm T, Amonsin A, Jam-on R, et al. Avian influenza H5N1 in naturally infected domestic cat. Emerg Infect Dis 2006;12:681-683.

6. Thanawongnuwech R, Amonsin A, Tantilertcharoen R, et al. Probable tiger-to-tiger transmission of avian influenza H5N1. Emerg Infect Dis 2005;11:699-701. Erratum in: Emerg Infect Dis 2005;11:976. Available at: www.cdc.gov/ncidod/EID/vol11no05/05-0007.htm. Accessed March 29, 2005.

7. Butler D. Can cats spread avian flu? Nature 2006;440:135.

8. European advice on H5N1 avian influenza in cats. Vet Rec 2006;158:314.

9. Kuiken T, Rimmelzwaan G, van Riel D, et al. Avian H5N1 influenza in cats. Science 2004;306:241.

10. Avian influenza fact sheet (April 2006).Wkly Epidemiol Rec 2006;81:129-136.

11. Perkins LE, Swayne DE. Varied pathogenicity of a Hong Kong-origin H5N1 avian influenza virus in four passerine species and budgerigars. Vet Pathol 2003;40:14-24.

12. Avian influenza backgrounder. Available at: www.avma.org/public_health/influenza/avinf_bgnd.asp. Accessed May 15, 2006.

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