Saturday, August 05, 2023

Eurosurveillance: Two Papers On HPAI H5N1 clade 2.3.4.4b virus in cats, Poland, June to July 2023


#17,601

We've been following the outbreak of H5N1 in cats in Poland since June 21st, unfortunately much of what has been reported has come from the media and other, non-official sources.  What we `know' is that at least 2 dozen cats (probably many more), from across the nation have died from H5N1, and that both indoor and outdoor cats have been affected. 

Poland's office of the Chief Sanitary Inspectorate last posted about this outbreak a month ago, and we've not seen an update posted on Poland's GIW (Chief Veterinary) website in nearly 3 weeks. 

Suggestions that the virus may have entered the food chain, have been met with strong resistance (see Poland : Ministry of Agriculture Statement On H5N1 & Food Safety), although it remains a likely (albeit, unproven) conduit for the virus.

In sharp contrast, earlier this week South Korea identified H5N1 in locally produced cat food after only a few days of investigating, prompting an immediate recall.

We've two related reports in this week's Eurosurveillance on the situation in Poland. 

First, an overview and virus analysis from Poland's National Veterinary Research Institute and their research partners, followed by a Rapid communication penned by Pyrc KrzysztofMaciej Grzybek & Lukasz Rabalski et al. who publicly raised concerns about the possibility of H5N1 in the food supply last month. 

Due to their lengths, I've only posted brief excerpts from each.  Follow the links to read them in their entirety. 

Euro Surveill. 2023;28(31):pii=2300366.
Key public health message

There was widespread information on social media in Poland about a violent, fatal cat disease with acute respiratory and neurological signs probably caused by avian influenza virus. The aim of the ongoing investigations was to confirm or exclude this information, characterise the identified virus and investigate possible sources of infection.

We detected the highly pathogenic avian influenza virus of the H5N1 subtype in 25 of 46 cats. Molecular analyses showed that it belongs to the genotype of a virus that previously circulated in wild birds and poultry in Poland and also contains several mutations that may increase adaptation to mammals. The viruses were very similar to each other, indicating a common source of infection, which, however, has not yet been identified.

The presence of similar viruses with mammalian-adapted features in so many cats is highly concerning. Although there are no reports of humans infected with this virus, such a risk exists especially for cat owners. Therefore, it is recommended to observe the health of feline pets, limit their contact with the outside environment and avoid feeding them raw poultry meat. 

(SNIP)

Setting

A national programme aimed at detection of HPAI virus infections in poultry and wild birds has been conducted in Poland for 20 years, since 2003. The obligation to conduct these surveys, as well as the detailed manner and mode of control of this disease, derives from the provisions of Commission Delegated Regulation (EU) 2020/689 of 17 December 2019 supplementing Regulation (EU) 2016/429 of the European Parliament and of the Council [4]. It includes both passive surveillance of HPAI virus in poultry and wild birds (testing of dead and sick birds) and active surveillance testing of live poultry from species that do not show typical symptoms following HPAI virus infection, as well as active surveillance of low pathogenic avian influenza virus (serology).
It is mandatory that all detected infections are notified, sequencing is performed on representative samples, and the sequences are then forwarded to the European Union Reference Laboratory (EURL) for Avian Influenza in Italy (Istituto Zooprofilattico Sperimentale delle Venezie) [5].
Apart from the aforementioned monitoring and veterinary surveillance in slaughterhouses for the clinical health status of animals, there are no other measures in place to prevent avian influenza entering the food chain. There is no monitoring of avian influenza infections in mammals in Poland.

          (SNIP)  

Molecular markers of virus adaptation in mammals

Amino acid differences identified in the viral proteins of the analysed viruses are detailed in Table 2. In particular, all the viruses possess mutation PB2-E627K, which is an important molecular marker of virus adaptation to mammals [13-23]. The same mutation was present in the H5N1 virus detected in the white stork at the beginning of June (A/white_stork/Poland/MB244/2023). This mutation has rarely been observed in H5N1 viruses collected from birds during the ongoing epidemic wave (0.16% of the viruses from birds) but has frequently been acquired by the virus after transmission to mammals (17% of viruses from mammals) [1]. Moreover, all the viruses from cats possessed mutation PB2-K526R, which is another marker of mammalian adaptation. Of note, the Polish H5N1 viruses from cats gained dual 526R/627K substitutions in the PB2 protein and are the only ones characterised during the 2.3.4.4b world-wide current epidemic wave showing both mutations.
(SNIP) 
Conclusions

Recently, there have been a number of worrying changes in the ongoing HPAI outbreak. Another such unusual situation has occurred in Poland – the unprecedented scale of HPAI H5N1 virus infections of cats. Although the most likely source appears to be poultry meat, no such meat has been identified to date. Surveillance of poultry should certainly be enhanced, but also for certain, susceptible species of farmed mammals kept close to infected poultry farms. In addition, it seems reasonable to carry out scientific research into the susceptibility to influenza of other animals, in particular small mammals such as moles or voles. Furthermore, this study highlights the need in Europe to include Mammalia in the group of species posing a considerable risk for the spread of HPAI, in order to provide health authorities with tools and guidelines for the proper management of such cases.

          (Continue . . . )




Euro Surveill. 2023;28(31):pii=2300390.

Since their emergence in poultry in Guangdong, China, highly pathogenic avian influenza A (HPAI) subtype H5N1 viruses have undergone a series of complex reassortments, leading to the development of multiple descendant lineages. Notably, starting December 2022 the clade 2.3.4.4.b has caused a widespread and unprecedented outbreak on a global scale among wild birds [1].

While HPAI H5N1 viruses are recognised as posing a risk for zoonotic disease and have been associated with severe illness, only 12 human cases attributed to the 2.3.4.4.b clade have been reported so far to the World Health Organization, including four cases of severe illness [2]. Following increasing numbers of cases observed among wild and farmed mammals, there has been a concern about spillover infections from wild birds to mammals. The widespread opportunity for exposure of mammals created by the worldwide dissemination of the HPAI H5N1 2.3.4.4.b viruses among wild birds also raises the issue of potential adaptation of HPAI H5N1 viruses, which could lead to their facilitated transmission among mammals [3-6].

Here, our group presents evidence of infections in domestic cats in Poland, which constitute a potential risk to both pet owners and veterinarians. As the sudden reporting of multiple cases across the country (28 domestic cats and one captive caracal [2]) is highly unusual, we conducted tests on cat food as a potential source of infection and successfully detected infectious HPAI H5N1 virus. 

         (SNIP)

Discussion
 

We report the detection and genetic analysis of HPAI H5N1 viruses in ill cats in Poland, within the context of a fatal disease outbreak that occurred in this country in June 2023. Based on an unofficial database created by cat owners, the distribution of cat cases suspected of being related to the outbreak appeared to be nationwide. Phylogenetic analyses suggest a monophyletic origin of the viruses affecting the cats, which were characterised as belonging to clade 2.3.4.4b with two mutations (E627K and K526R) in PB2, considered to be mammalian adaptation markers. Based on available data, the cat-derived viral sequences appeared closely related to an HPAI H5N1 virus sequence derived from a stork, which was also clade 2.3.4.4b. This sequence nevertheless only bore the K526R mutation.

Reaching out to owners whose cats had experienced an illness compatible with HPAI H5N1 infection, some samples from food that these animals had reportedly consumed prior to the emergence of symptoms were obtained and tested. A virus with high degree of similarity to the cat viruses and bearing the E627K and K526R was found in chicken meat from the same household as an ill cat, suggesting, but not confirming, a possible route of transmission. An HPAI H5N1 virus isolate from the chicken meat juice demonstrated the ability to infect both canine and feline cells, and efficiently infected and damaged human airway epithelia in cell culture.

This study has some limitations. The virus found in a chicken meat sample originated from a private refrigerator of one of the cat owners; its origin cannot be confirmed, and it is essential to consider that it might have been contaminated post-butchery, during transport, or at the household. The meat samples under investigation were sourced from households where severe illness was reported in cats. However, these cases were not conclusively identified as being infected by HPAI H5N1 virus; it is also important to note that the meat samples analysed were not necessarily the sole variety of meat these cats consumed. The public database mentioned in this report relied upon is a community initiative by cat owners that has not undergone any form of curation. Caution should therefore be exercised when interpreting the data. Nevertheless, in the early stages of an outbreak, such an initiative can swiftly provide critical information and serve as a valuable resource.
Conclusion

Considering the presented data, we recommend that the presence of the virus should be assessed in both wild and farmed settings and other locations where potential virus adaptation may occur. Taking into account non-food-related routes of transmission, environmental testing may be recommended, as well as testing of wild birds with no apparent pathology. Further epidemiological analysis might reveal possible links between the cases and, subsequently, shed more light on the source of infection.

         (Continue . . . )


Everyone seems to agree that this outbreak of H5N1 in cats is unprecedented, and that the unique dual  mammalian adaptations (526R/627K substitutions in the PB2 protein) are concerning, but we know little more about how this virus is spreading to cats than we did a month ago. 

While this outbreak appears to have peaked in the middle of last month, and the focus of our attentions will likely quickly shift to the next mammalian spillover event somewhere in the world, figuring out what happened in Poland is still important.  

Because our best defense against this virus is understanding everything we can about it, and (hopefully) finding ways to prevent its spread.