Friday, February 18, 2022

Two Reports On HPAI H5N8 Infecting Marine Mammals (Denmark & Germany)

Photo Credit Wikipedia


Following nearly 3 years of reduced activity, Europe is in the midst of its 2nd record-setting avian H5Nx epizootic since the fall of 2020, and unlike during previous events, we are seeing increased signs of avian flu spillover into mammalian species.  Some recent blogs include:

Netherlands DWHC Reports another Mammal (Polecat) Infected With H5N1

Netherlands: WBVR Diagnoses Avian H5N1 In Another Fox

CDC EID Journal: Encephalitis and Death in Wild Mammals at An Animal Rehab Center From HPAI H5N8 - UK

EID Journal: HPAI A(H5N1) Virus in Wild Red Foxes, the Netherlands, 2021

In addition to these species jumps, we've also seen increasing reports of unexpected neurological manifestations, such as walking in circles, falling over, and blindness. Symptoms that have previously been reported with some Asian H5N1 viruses, but not in the milder (clade Eurasian lineages. 

In the 2015 report Highly Pathogenic Avian Influenza A(H5N1) Virus Struck Migratory Birds in China in 2015, the authors wrote:

This suggests that the novel Sanmenxia Clade H5N1 viruses possesses tropism for the nervous system in several mammal species, and could pose a significant threat to humans if these viruses develop the ability to bind human-type receptors more effectively.

It was barely a year ago that we learned of the first human infections with H5N8 (see Russian Media Reports 7 Human Infections With Avian H5N8) which led to the classification of the Eurasian H5N8 as having some zoonotic potential (see CDC Adds Zoonotic Avian A/H5N8 To IRAT List).

Subsequently, a small number of H5N1 human infections have been reported in Nigeria, and in the UK.  But unlike the reports on mammalian infections above, have either been described as mild, or asymptomatic. 

All of this led the ECDC/EFSA to Raise The Zoonotic Risk Potential Of Avian H5Nx last December, citing both the Russian and Nigerian human infections, and the recent spate of detections among mammalian species.  

Prior to 2020, we had only seen a few instances of species jump with the Eurasian H5Nx virus, mostly  in marine mammals These outbreaks likely happen more often than we know, but some documented examples involving a variety of novel flu subtypes include:

In 2021 there were multiple reports of species jumps to marine mammals, including to 4 seals (and a fox) in the UK, to a seal in Sweden (see DEFRA Report), and last September's Germany: Media Reports of Dead Seals Found Infected With Avian H5N8

Since species jumps can provide avian viruses with new opportunities to evolve via host adaptations, we monitor them with considerable interest. 

All of which brings us to two new reports of HPAI infection in marine mammals.  First, a report in Emerging Microbes & Infection describing fatal CNS infections in seals from HPAI H5N8, along with potentially significant mammalian adaptations  (PB2 E627 K) in the virus 

This is a lengthy, and detailed report, and very much worth reading in its entirety. 


Accepted author version posted online: 17 Feb 2022


In brain tissue of three harbor seals of the German North Sea Coast, high virus loads of highly pathogenic avian influenza virus (HPAIV) H5N8 were detected. Identification of different virus variants indicates high exposure to HPAIV circulating in wild birds, but there is no evidence for H5 specific antibodies in healthy seals. Replication of avian viruses in seals may allow HPAIV to acquire mutations needed to adapt to mammalian hosts as shown by PB2 627 K variants detected in these cases.


Discussion and conclusions

This study describes unusual infections of three adult harbor seals from the German Wadden Sea with HPAIV H5N8 of clade Most closely related viruses circulate in wild water birds around the North Sea since fall 2020. Serological investigations did not provide evidence for a wide distribution of these viruses in healthy seals. 

Similar to very recently reported findings in captive seals in the UK [7], our results show that HPAIV H5N8 of clade can induce fatal CNS infections in seals under natural conditions.  


Two HPAIV isolated from the German seals contain the PB2 E627 K mutation implicated in adaptation to mammalian hosts. The genetic findings underline the role of seals as a putative “adaptive vessel” for avian influenza viruses and the importance of surveillance in wild bird and mammal populations.

As we've discussed often (see Nature Comms: Host Adaptation Of Avian Influenza Viruses), while the impact of many influenza virus mutations remain a mystery, a number have been recognized as providing an advantage in mammalian hosts.  

Researchers have determined the (E627K) substitution in the (PB2) protein - the swapping out of the amino acid Glutamic acid (E) at position 627 for Lysine (K) - makes the an influenza virus better able to replicate at the lower temperatures (roughly 33C) normally found in the upper human respiratory tract (see Eurosurveillance: Genetic Analysis Of Novel H7N9 Virus).

 Our second report comes from Denmark's Veterinary Consortium, and is published on the SSI website. 

Bird flu in Danish seals

The Danish Veterinary Consortium has detected so-called highly pathogenic bird flu virus of the subtype H5N8 in a harbor seal. This is the first time that highly pathogenic avian influenza virus has been found in seals in Denmark.

Last edited 17 February 2022

Bird flu has been detected in a Danish harbor seal. The seal was found dead on a beach on Southwest Funen in September 2021 and examined at the Center for Diagnostics at DTU as part of the disease monitoring of fallen game.

The seal was emaciated with pronounced skin changes on large parts of the body of uncertain significance and cause. Influenza virus was detected in the lung, but otherwise no other disease-causing organisms could be detected that could explain why the seal was dead.

The Center for Diagnostics at DTU has stated that they have examined 29 harbor seals and 15 gray seals in 2021, of which only this one was positive for influenza virus. 
Turned out to be bird flu

Upon further investigation at the Danish Veterinary Consortium, the virus turned out to be highly pathogenic avian influenza virus of the subtype H5N8.

The detected virus is closely related to the viruses that have been the cause of outbreaks of bird flu in wild birds and domestic poultry since the autumn of 2020, both here and in the rest of Europe.
Seals are susceptible to bird flu

Seals are known to be susceptible to avian influenza virus.

In recent seasons with avian influenza in birds, the discovery of highly pathogenic avian influenza in wild mammals has been increasingly reported. Including seals and wild foxes in northern Europe. These findings have been primarily in animals with neurological symptoms, or who were found dead.

When mammals are infected with viruses from birds, there is a risk that the virus will mutate and adapt to its new host species and mammals in general. The Danish Veterinary Consortium has performed a detailed analysis of the virus genome from the wild seal and found some mutations in the virus that show signs of possible adaptation to mammals, although it was not possible to analyze the full genome due to the quality of the material.

Highly pathogenic bird flu in birds in Denmark since 2020
Denmark was hit by a serious outbreak of highly pathogenic bird flu, which stretched from autumn 2020 to July 2021. Here, highly pathogenic bird flu was found in 16 poultry herds and more than 300 wild birds.
Highly pathogenic bird flu has been detected again in wild birds and in poultry herds since the beginning of November 2021, and there are currently new finds in wild birds every week. So far, a total of 10 crews have been hit this season. The latest just a few days ago.

Viruses in both seasons are related and belong to the variant of H5 highly pathogenic bird flu called clade While it was primarily viruses with the H5N8 subtype that were found last season, it is by far the predominant H5N1 virus that has hit this season.

Avoid touching dead animals

Avian influenza virus can rarely infect humans. One should therefore avoid touching dead or sick wild animals.

The international health authorities continuously monitor the situation and currently assess that the risk of infection with avian influenza virus to the general population is low. The risk can be reduced for people exposed to potentially infected birds by using personal protective equipment.
Tip The Danish Veterinary and Food Administration about dead birds

If you find a dead bird in the wild, you are very welcome to tip the Danish Veterinary and Food Administration about your find. Feel free to use the app 'Bird Flu Tip'.

The Danish Veterinary and Food Administration would especially like to tip about the discovery of several dead ducks, geese, swans or gulls in one place or about the discovery of a few dead birds of prey and crows.

Let the birds lie

The Danish Veterinary and Food Administration ensures that the birds that are relevant to examine for bird flu are collected and that they are submitted for examination at the University of Copenhagen and the Statens Serum Institut.
          (Continue . . . )

For now the Eurasian clade lineage of HPAI H5Nx appears to pose a minimal threat to human health, and most of the health warnings are made out of an abundance of caution.   

But last May, in Science: Emerging H5N8 Avian Influenza Viruseswe looked at a review by two well-respected Chinese scientists (Weifeng Shi and George F. Gao)  on the evolution, and growing zoonotic threat, of avian H5N8, stating:

  •  the  ". . . global spread of AIVs, particularly the H5N8 subtype, has become a major concern to poultry farming and wildlife security but, critically, also to global public health."
  • And due to the ". . . long-distance migration of wild birds, the innate capacity for reassortment of AIVs, the increased human-type receptor binding capability, and the constant antigenic variation of HPAIVs  the authors warned that it was imperative that " . . . the global spread and potential risk of H5N8 AIVs to poultry farming, avian wildlife, and global public health are not ignored."
And in June, in V. Evolution: Genomic Evolution, Transmission Dynamics, and Pathogenicity of Avian H5N8 Viruses Emerging in China, 2020, we saw Chinese researchers describe the rapid rise in 2020 of an antigenically distinct H5N8 virus that is lethal to chickens and mice, that is similar to the Russian Zoonotic strain, and has shown signs of mammalian adaptation.

So we treat these reports seriously, since we can't know when - or in what direction - the next reassortment event or series of mutations will take this virus subtype.