Cats As Potential Vectors/Mixing Vessels for Novel Flu
#18,384
We've known for 20 years that cats - both large and small - are susceptible to HPAI H5 infection (see 2004 CIDRAP Report) and have seen scattered reports over the years (see 2015's HPAI H5: Catch As Cats Can).
Up until a few years ago, those reports were relatively rare, and mainly came from zoo animals fed on a diet of raw chicken. But since the emergence of a new, more transmissible H5N1 virus in 2021, the number of companion animals (and other mammals) reported to be infected has risen sharply.
In 2023 we saw two high profile outbreaks; in Poland and in South Korea. While the South Korea outbreak was quickly traced to locally produced cat food, we've heard very little from Poland's investigation.
Here in the United States the USDA lists 53 domestic cat deaths due to H5N1, along with roughly 3 dozen other felines (mountain lions, bobcats, etc.). This is almost certainly an undercount, as many wild or stray animals die in remote places and are never tested, and some cats are known to survive H5N1 infection.
Last November we looked at plans by Utrecht University to Study Stray & Domestic Cats For Evidence Of HPAI H5N1 Exposure, which reported:
Previous research by the Faculty of Veterinary Medicine among 1,500 cats in the period 2020-2023 found cats with antibodies against the bird flu virus. This mainly concerns stray cats (without owners). During a castration project, these cats were examined for antibodies against various viral infections, including bird flu. The stray cats came from 72 different locations.
Of the 701 stray cats examined, 83 stray cats were found to have antibodies against the bird flu virus. A number of the stray cats examined had mild symptoms, but not specifically for bird flu. Eating infected dead birds is a likely route of infection for these stray cats. An analysis of various risk factors showed that stray cats from nature reserves had, on average, more antibodies against the bird flu virus than stray cats from other habitats, such as a livestock farm, holiday park or industrial area.
In domestic cats, 4 of the 814 blood samples examined had antibodies against the bird flu virus. The blood samples from the domestic cats were sent to the Faculty for blood testing for various reasons. These were therefore not part of the castration project, but were added to this part of the study as a control group. Among domestic cats, there was an overrepresentation of cats from urban areas in the Randstad and it is not known whether these cats came outside and therefore possibly had contact with (wild) birds. The faculty wants to gain more insight into this with the new research into domestic cats that come outside. The study is expected to be completed by mid-2024.
Yesterday that research was published in the journal Eurosurveillance. This is a lengthy, and detailed, report and I've only posted some brief excerpts. Follow the link to read it in its entirety.
I'll return with a postscript after the break.
Highly pathogenic avian influenza (HPAI) H5 virus exposure in domestic cats and rural stray cats, the Netherlands, October 2020 to June 2023
Mirjam B H M Duijvestijn1 , Nancy N M P Schuurman2 , Johannes C M Vernooij3 , Michelle A J M van Leeuwen4 , Judith M A van den Brand5 , Jaap A Wagenaar1 , Frank J M van Kuppeveld2 , Herman F Egberink1,2 , Cornelis A M de Haan2 , Josanne H Verhagen1,2
Key public health message
What did you want to address in this study and why?
Highly pathogenic avian influenza (HPAI) viruses have spread among poultry and wild birds. Avian and human influenza viruses can infect cats, and cats may function as a source of novel influenza A viruses to humans. We analysed serum samples, throat and lung samples from domestic and stray cats to investigate exposure to influenza viruses and associated factors.
What have we learnt from this study?
Of the 701 stray cats sampled, 83 had been exposed to HPAI virus, whereas only four of the 871 domestic cats. Exposure was more common in older cats and cats living in nature reserves. Some stray cats had been exposed to both avian and human influenza viruses. In contrast, 40 domestic cats were exposed to human influenza viruses.
What are the implications of your findings for public health?
We showed that cats in the Netherlands were exposed to human and/or avian influenza viruses. We recommend close monitoring of infections with influenza viruses in cats and protective measures when handling suspected cats. Further studies are needed to understand how cats become infected and whether cats can transmit highly pathogenic avian influenza virus to other animals or humans.
(SNIP)
Discussion
In this study, stray cat and domestic cat sera collected in the Netherlands 2020–2023 were analysed for antibodies to HPAI H5 and H1 virus. Our results showed that HPAI H5 exposure was common in stray cats and rare in domestic cats.
The different proportion of seropositivity for HPAI H5 virus in stray cats and domestic cats in our study, may reflect differences in exposure to birds. Given their reliance on predation or scavenging for survival, stray cats that feed on prey, including birds [32], face an increased risk of HPAI H5Nx exposure compared with domestic cats that are fed and predominantly stay indoors.
The HPAI H5 seropositivity of 11.8% in clinically healthy stray cats contrasts with recent case reports describing HPAI H5Nx infections in cats resulting in severe disease and death [8,10,12-15]. However, antibodies to HPAI H5 have been reported in clinically healthy cats [11,18,19,33]. Important explanatory factors for these conflicting results may be related to differences in transmission route, viral dose, or other, not yet known, predisposing factors.
(SNIP)Experimental intranasal, oral or enteral infections all resulted in respiratory and extra-respiratory clinical signs, and these cats died or were euthanised within 7 days [20,21,34-36]. However, the occurrence and severity of clinical signs in cats infected with HPAI H5N1 clade 2.2.2 appeared dose-dependent [37]. We therefore hypothesise that the presence of HPAI H5 antibodies in clinically unaffected stray cats or stray cats that survived infection, may be the result of exposure to a low viral dose.
We found several factors that were associated with an HPAI H5 seropositivity in stray cats. The highest HPAI H5 seropositivity was found in cats living in nature reserves (37.8%) and on dairy farms (11.0%). The higher HPAI H5 seropositivity in stray cats in nature reserves, compared with cats at other locations may be partly explained by the availability of food. Cats in nature reserves depend on scavenging and hunting to survive. Moreover, diseased or dead birds may be removed at locations with human activity, while they may remain longer present in nature.Although avian-to-cat contact may have resulted in HPAI H5 infection in cats living on dairy farms, recent reports point to an alternative route of exposure [8]. In the US, cats on dairy farms with cows infected with HPAI H5N1 became infected via ingestion of raw milk [8]. Cattle infected with HPAI H5 virus have not been detected in the Netherlands, but this needs further investigation.In older cats, a prolonged exposure period or multiple exposures may explain the higher proportion of HPAI H5 seropositivity. Additionally, older cats are more experienced hunters and have larger home ranges [27] which may affect exposure to birds or viruses. Furthermore, antibodies to FIV were detected in 34 of 664 (5.1%; 95% CI: 3.6–7.1%) stray cats. Immunodeficiency due to FIV, reported in stray cats in the Netherlands previously [27], is associated with an enhanced susceptibility to other pathogens. This may explain the higher HPAI H5 seroprevalence in FIV-positive stray cats.
The difference in stray cat HPAI H5 seropositivity needs to be interpreted with caution. The convenience sampling of stray cats during trap-neuter-return-and-care activities and the targeted sampling in 2023 in our study may have resulted in a selection bias [27]. The distribution of sampling locations, sampling month, as well as the location type differed per year. Sampling intact, younger stray cats may have resulted in an underestimation of the HPAI H5 seroprevalence, as older age was associated with an elevated HPAI H5 seroprevalence. Seroprevalence studies on domestic cats that have outdoor access, especially in rural areas, are needed to further assess their risk of HPAI H5 virus exposure.
Conclusion
Stray cats in the Netherlands are commonly exposed to HPAI H5 with a high seropositivity in cats in nature reserves. We recommend close monitoring of IAV infections in stray cats and in domestic cats that have outdoor access, especially in areas where HPAI H5 virus positive wild birds are present. When these cats present with neurologic or respiratory clinical signs, we advise to handle these cats using personal protective equipment. Further studies should focus on virus excretion to explore if these cats can transmit viruses to other mammals or to humans. Furthermore, our findings warrant further investigation in the potential role of cats as IAV mixing vessels.
Given how severe, and often lethal, HPAI H5 infection appears to be in felines, the discovery that 12% of stray, healthy looking, cats in this sampling carried H5 antibodies is surprising. The authors suggest that these felines may have been exposed to a low viral dose.
Which suggests that when you add in the (uncounted) fatal cases, the infection rate is likely far higher than 12%.
Equally curious, the authors report `. . . highest HPAI H5 seropositivity was found in cats living in nature reserves (37.8%) and on dairy farms (11.0%).' While we've seen no evidence of HPAI H5 in European dairy cows, over the summer Germany's FLI reported On Experimental Infection Of Dairy Cows With European H5N1 Virus.
As a first interim result, not only the US isolate but also a recent H5N1 virus from a wild bird in Germany was able to multiply very well in the udder. Following direct infection of the udder through the teats, the dairy cows in both cases showed clear signs of disease such as a sharp drop in milk production, changes in milk consistency and fever.The FLI stated `. . . increased vigilance is recommended and HPAI H5 should also be considered in investigations, especially in the case of unclear and frequent cases of disease in dairy herds'.
While the CDC maintains that the risk to the general public from H5N1 remains very low, it is not zero, and they offer the following advice to pet owners.As the authors suggest, this finding merits further investigation.
Pet Owners
If your domestic animals (e.g., cats or dogs) go outside and could potentially eat or be exposed to sick or dead birds infected with bird flu viruses, or an environment contaminated with bird flu virus, they could become infected with bird flu. While it's unlikely that you would get sick with bird flu through direct contact with your infected pet, it is possible. For example, in 2016, the spread of bird flu from a cat to a person was reported in NYC. The person who was infected [2.29 MB, 4 pages] was a veterinarian who had mild flu symptoms after prolonged exposure to sick cats without using personal protective equipment.
If your pet is showing signs of illness compatible with bird flu virus infection and has been exposed to infected (sick or dead) wild birds/poultry, you should monitor your health for signs of fever or infection.
For more on companion animals and H5N1, you may wish to revisit:
Emerg. Microbes & Inf.: Characterization of HPAI A (H5N1) Viruses isolated from Cats in South Korea, 2023
ECDC Risk Assessment: Avian influenza in domestic cats - Poland - 2023
Eurosurveillance: Asymptomatic infection with clade 2.3.4.4b HPAI A(H5N1) in carnivore pets, Italy, April 2023