Monday, December 11, 2023

J. Virulence: HPAI H5N1 Virus Infection In Companion Animals

Cats As Potential Vectors/Mixing Vessels for Novel Flu


We've known for two decades that large cats in captivity (when fed infected poultry) can contract HPAI H5N1 (see 2004 CIDRAP Report), and we've seen scattered reports of dogs and cats infected with the virus (see 2015's HPAI H5: Catch As Cats Can) in the years since.  

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. 

A few (of many) reports include:

Infections have ranged from asymptomatic (in dogs and cats in Italy) to severe and often fatal in other countries, and in many cases genomic analysis has shown evidence of mammalian adaptations in the avian H5 virus. 

Despite this steep increase in reports, it is likely that many cases have gone unreported. 

While the risks to humans from H5N1 remains quite low, that risk is arguably higher for dogs and cats which are allowed outside (see Netherlands: Utrecht University Study Of Stray & Domestic Cats For Evidence Of HPAI H5N1 Exposure).  

Since people have contracted avian flu from pets in the past (see J Infect Dis: Serological Evidence Of H7N2 Infection Among Animal Shelter Workers, NYC 2016), we've seen guidance from the CDC (see Bird Flu in Pets and Other Animals) and the UK's DEFRA on the importance of keeping pets safe from H5N1.

Today we have a combination Editorial/Review of HPAI H5 infection in companion animals by Professor Hinh Ly of the Department of Veterinary and Biomedical Sciences at the University of Minnesota.

This review provides us with an excellent overview of H5N1 in companion animals, updates and analysis of several of the outbreaks mentioned above (France, Italy, Poland, Nebraska), along with a cautionary statement that H5N1 will likely continue to evolve and adapt to new animal hosts. 

I've only posted some excerpts from a much longer article, so follow the link to read it in its entirety.  I'll have a brief postscript after the break. 

Highly pathogenic avian influenza H5N1 virus infection of companion animals

Hinh Ly
Article: 2289780  Published online: 08 Dec 2023

While it is known that influenza viruses can frequently infect a variety of animal species, including humans (for a review, see ref. [Citation1]), it is relatively uncommon for companion animals (e.g. pet cats and dogs) to be infected by the highly pathogenic avian influenza (HPAI) H5N1 virus. This article summarizes our current understanding of HPAI H5N1 infections in pets with the aim of raising awareness about these emerging and re-emerging infections in domestic animals.



Figure 1 of 1

Figure 1. Influenza a (IAV) and influenza B (IBV) virus infections of humans and animals (e.g. avian, swine, canine, feline, and other animal species) to cause seasonal (epidemic) human infections or occasional outbreaks (Spanish flu, Asian flu, Hong Kong flu, and swine flu) that were caused by the different subtypes of human IAVs. Almost all subtypes of IAV (H1-H16, N1-N9) have water birds as their natural hosts, with some IAVs (e.g. the highly pathogenic avian influenza virus HPAI H5N1) capable of infecting other animal species, such as large felids (tigers and leopards) and domestic dogs and cats, and farmed animals (chickens, turkeys, ducks, and mink) as well as humans with a high case fatality rate. Drawing adapted from ref. [Citation1] with modifications using Biorender.


Zoonotic influenza infections usually occur through occasional viral transmission from either avian or swine species to humans (Figure 1), but these types of infections are usually self-limiting. However, certain types of IAVs, such as avian H5 and H7 viruses, are known to cause hundreds to thousands of infections, with a high case fatality rate (30–50%) in humans (for a review, see ref. [Citation5]). Therefore, the possibility that some of these highly pathogenic avian (HPAI) viruses can gain a foothold in human populations to mediate efficient human-to-human transmissions and a potential pandemic poses a significant public health risk [Citation6]. 

Notably, since the initial report of human fatalities caused by the HPAI H5N1 infections in Hong Kong in 1997, there have been at least 878 cases of human H5N1 infections worldwide, resulting in a mortality rate of 52.16% (– 2003–2023–14 July 2023).
However, it is relatively uncommon to learn about HPAI H5N1 infections of other animal species besides known human cases and, of course, their natural avian host species until recent years. Since 2021, at least 12 different animal species, including some companion animals, such as household cats and dogs, have been reported to be infected by the HPAI virus H5N1 in more than nine countries ( July 2023-ongoing-avian-influenza-outbreaks-in-animals-pose-risk-to-humans).


Cases of HPAI H5N1 virus infections in domestic cats in the USA, France, and Poland described above [Citation7,Citation10,Citation22] as well as in farmed fur animals (mink) in Finland and Spain [Citation23,Citation24] showed overt clinical manifestations characterized by severe respiratory distress and neurological signs, but the affected pets (dogs and cats) reported from Italy [Citation18] were completely asymptomatic, raising a real concern for the possibility of subclinical infections of HPAI H5N1 viruses in domestic animals that might live in close proximity and/or have had frequent and direct contact with humans, which could lead to inadvertent zoonotic transmissions.
Since the infection and transmission routes of these highly pathogenic avian influenza viruses in some farmed animals (e.g. mink) and companion animals (pet cats and dogs) are still poorly understood, additional surveillance efforts and experimental research on HPAI H5N1 infection of susceptible animal species are needed to fully understand the ecology, possible transmission routes, and disease pathogenesis of these HPAI H5N1 viruses to prevent potential future outbreaks.
It is important to note that domestic animals, such as pet cats, in other parts of the world (e.g. Asia) have previously been shown to be naturally susceptible to HPAI H5N1 infections (for a review, see ref. [Citation25]. Several years after the reported outbreak of HPAI H5N1 infections in humans in Hong Kong in 1997, this virus re-emerged in Asia, causing high mortality rates in poultry in addition to being responsible for acute respiratory infection in humans. Notably, the Asian HPAI H5N1 virus was also found to infect and kill mammals other than humans and birds. These animals included large cats (tigers), domestic cats, and other felids. Several outbreaks of fatal diseases caused by the Asian HPAI H5N1 viruses in large felids (tigers and leopards) and domestic dogs and cats have been reported in Thailand [Citation26,Citation27].
Therefore, if history is a guide, we can reasonably expect that the continuous evolution of HPAI H5N1 viruses through mutations, including antigenic shifts and drifts, will allow them to adapt to different animal hosts that include but are not necessarily limited to mammals (e.g. household pets) and to cross country boundaries or leap across vast distances between continents.

         (Continue . . . )

Companion animals are just one of a number of plausible routes the H5N1 virus could take to achieve mammalian adaptation (see graphic below).

Farmed mink (see PNAS: Mink Farming Poses Risks for Future Viral Pandemics) and swine  (see Seroconversion of a Swine Herd HPAI H5N1 Clade Virusrank high on our worry list, as does the massive impact of H5N1 on marine mammals

It is also entirely possible that H5N1 could reassort with human seasonal influenza (H1N1 or H3N2), creating a new hybrid virus.  While this might produce a less severe pathogen than an adapted H5N1 virus, it could be a convenient shortcut for the virus. 

It is for this reason that people who work with poultry or swine are strongly urged to get the seasonal flu vaccine (see Canada: BC Provincial Health Officer Urges People Living/Working On Poultry Farms To Get Seasonal Flu Vaccine).  Of course, in many countries, that isn't even offered. 

While it is still a long-shot that H5N1 will spark a pandemic, it continues to find new avenues to explore and exploit, and it only has to get `lucky' once.

Meanwhile, we not only have to stay `lucky' with regards to H5N1, we need the same good fortune against an expanding array of emerging viral, bacterial, and fungal pathogens. 

Which is why, in 2021's PNAS Research: Intensity and Frequency of Extreme Novel Epidemics, researchers estimated our pandemic risk may increase 3-fold over the next few decades.