Subclinical Infection With Avian Influenza A (H5N1) Virus in Cats

Michael Leschnik; Joachim Weikel; Karin Möstl; Sandra Revilla-Fernández; Eveline Wodak; Zoltan Bagó; Elisabeth Vanek; Viviane Benetka; Michael Hess; Johann G. Thalhammer

Disclosures

Emerging Infectious Diseases. 2007;13(2):243-247. 

In This Article

Discussion

This is the first description of an asymptomatic infection with highly pathogenic H5N1 influenza virus in domestic cats. Although infection was detected in a group of cats by positive PCR results for pharyngeal swabs in 3 cats and seroconversion in 2 cats, there was no evidence for influenza-associated disease. This finding contrasts with reports documenting cats with rapidly and developing and fatal disease caused by influenza A virus subtype H5N1.[3,4,5,7] High fever, depression, severe pneumonia, pulmonary edema, nonsuppurative encephalitis, and sudden death were observed after natural[5] or experimental infections.[3,7] Infection with influenza virus H5N1 was shown to cause severe lower respiratory tract disease as well as systemic disease that affected many organs outside the respiratory tract, which could explain the increased pathogenicity of this virus for other organ systems.[3,17]

During the observation period, episodes of sickness including respiratory symptoms (mild dyspnea, conjunctival, and nasal discharge), oral mucosal lesions, and diarrhea were observed in cats in both groups in the animal shelter and in the quarantine station. A long (12 hours) and uncomfortable transport to the quarantine area, social distress caused by high population density, repeated restraint for examinations and sample collection, and multiple infectious agents may have caused such a high level of illness. Twelve cats died or were humanely killed while in a moribund state between days 22 and 50. All showed signs of disease other than infection with influenza virus A and died of feline infectious peritonitis, cardiomyopathy, enteritis, or nephropathy; none tested positive for H5N1 virus.

During the observation period from days 22 to 50, excretion of virus was not detected in the pharynx or feces. Positive results were observed only on day 8 for 3 of the randomly sampled swabs. Therefore, viral shedding is assumed to have lasted <2 weeks in cats 1 and 2. In 1 study, no information was reported on the duration of virus shedding because only severe illness with a lethal outcome was reported or the cats were killed 7 days after experimental infection.[3] Because seroconversion was confirmed in only 2 animals, horizontal transmission within the group of 194 cats is unlikely. This conclusion is consistent with the finding that no virus shedding could be demonstrated after day 8, but it contrasts with the results of Rimmelzwaan et al.,[3] who demonstrated horizontal transmission from experimentally infected cats to sentinel cats, and results of studies in mice and ferrets.[18,19] After infection by the oral or intratracheal route, cats developed viremia; virus spread into different tissues and was excreted in feces and saliva.[7] High viral load and differences in virus strains could result in different host reactions.

The reason for limited horizontal transmission in our study could be low-level virus shedding by the initially infected cats. Initial virus load, route of virus uptake, and the immune system of the cat may affect infection and disease. Otherwise, the lack of illness would be unusual because several cats in the study had immunodeficiencies caused by other infectious diseases.[20,21]

An asymptomatic infection confirmed by seroconversion is assumed for cats 1 and 4. The situation for cat 2 is not as clear. It is unlikely that the positive PCR result in the swab sample from cat 2 is due to contamination and is a false-positive result. Conversely, infection could not be confirmed by seroconversion. It remains unclear whether ongoing infection could be stopped (possibly by interferons) or whether the cat did not produce sufficient amount of antibodies. Little information is available on immune responses after infection with influenza virus H5N1 in cats.

H5N1 virus can cross species barriers[22] and infect new hosts. Transmission from poultry to mammals, between cats,[3,5,7,8] and between humans[23] indicates 2 routes of virus uptake under natural conditions. The first is orally by ingestion of raw poultry, and the second is transmission by contact with feces or saliva of infected animals. In our study, virus transmission from infected poultry to cats must have occurred from days 1 to 4. Uptake of H5N1 virus by ingestion of infected poultry can be ruled out. We observed only some cats entering the area where the birds were housed. Therefore, the most likely route of transmission for these cats is contagious fecal contamination of the hair and oral uptake during grooming. However, we cannot exclude aerosolization of the virus as a route of transmission.

Until recently, the avian flu situations in Asia and Europe appeared to differ. In Asia, large numbers of poultry have been infected and culled. Human and feline cases are mainly associated with close contact with infected poultry or ingestion of contaminated meat that was not sufficiently cooked. In Europe, mainly wild aquatic birds were infected, and only a few turkey farms were affected by H5N1 infection. Because direct contact with poultry is more limited in Europe than in Asian countries and the main source of food for cats in Europe is either commercial cat food or wild rodents and small birds, virus uptake during hunting and ingestion of poultry and aquatic birds is unlikely. Large aquatic birds are normally not a major source of food for cats, although infected birds may have caused the deaths of 3 cats found on the island of Ruegen, Germany.[4]

We have shown that under natural conditions infection of cats with influenza virus H5N1 may occur after contact with infected birds or their excrement without inducing clinical disease. However, horizontal transmission between cats was not observed, although infected cats had been introduced into a large cat population that had other viral and bacterial infections and lived under stressful conditions. Avian flu infection in cats is rarely documented and there is no evidence to date that cats are responsible for transmitting the virus to humans. Although this study does not rule out H5N1 infection leading to disease and possible transmission to other mammals and birds by domestic cats under natural conditions, without ingestion of infected birds, cats do not represent a major risk in the epidemiology of H5N1 influenza. The risk posed by cats could change because the virus can rapidly undergo genetic mutation and reassortment, and efforts should be made to minimize contact of domestic cats with infected birds. To have better insights into whether cats represent a potential risk in the epidemiology of H5N1 influenza, more detailed knowledge is needed about the role of viral load, virus uptake, and immune mechanisms of the host on the outcome of infection with H5N1 influenza virus.

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