CDC Report & Risk Assessment On Potential Influenza Infection Via GI Tract

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One of the topics we've touched on repeatedly over the past twenty years has been the - as yet, unquantified - risks of preparing, and consuming  animal products (meat, eggs, milk, etc.) which may be infected or contaminated with HPAI viruses. 

We've known for more than 20 years what happens when cats are fed raw (fresh or frozen) H5N1 contaminated, poultry (see HPAI H5: Catch As Cats Can), with the most recent report issued less than a week ago (see FDA Issues New Warning On H5N1 Detected In Cat Food).

Since then, we've seen evidence that other mammalian species are susceptible to HPAI virus via the GI tract as well (see Research: Ferret H5N1 Infection Via Consumption Of Infected Chicken).

While reports of human infection via the consumption of contaminated food products are harder to pin down, we've seen a number of `suspicious' incidents where ingestion and absorption of HPAI via the GI tract could not be ruled out (see 2007's Don't Order The Beggar's Chicken).

In 2008's Clinical Case Review Of 26 Chinese H5N1 Patients, we saw a review that mentioned a number of `atypical' symptoms in HPAI cases, citing:

Diarrhea was present in only two H5N1 cases at admission, but developed in a quarter of cases during hospitalization. Diarrhea was a common presenting symptom among H5N1 cases in Vietnam and Thailand, but was reported infrequently among cases in Hong Kong SAR, China, and Indonesia .

H5N1 virus and viral RNA have been detected in feces and intestines of human H5N1 cases . Whether the gastrointestinal tract is a primary site for H5N1 virus infection is currently unknown.

Two years later, in H5N1 Can Replicate In Human Gut, we looked at the following study published in the J. Infectious Diseases.

Avian influenza A(H5N1) viruses can directly infect and replicate in human gut tissues

Yuelong Shu 1, Chris Ka-fai Li, Zi Li, Rongbao Gao, Qian Liang, Ye Zhang, Libo Dong, Jiangfang Zhou, Jie Dong, Dayan Wang, Leying Wen, Ming Wang, Tian Bai, Dexin Li, Xiaoping Dong, Hongjie Yu, Weizhong Yang, Yu Wang, Zijian Feng, Andrew J McMichael, Xiao-Ning Xu
Affiliations ExpandPMID: 20210629
DOI: 10.1086/651457

Abstract

The human respiratory tract is a major site of avian influenza A(H5N1) infection. However, many humans infected with H5N1 present with gastrointestinal tract symptoms, suggesting that this may also be a target for the virus. In this study, we demonstrated that the human gut expresses abundant avian H5N1 receptors, is readily infected ex vivo by the H5N1 virus, and produces infectious viral particles in organ culture. An autopsy colonic sample from an H5N1-infected patient showed evidence of viral antigen expression in the gut epithelium. Our results provide the first evidence, to our knowledge, that H5N1 can directly target human gut tissues.

While anecdotal reports suggest that a significant number of H5N1 cases over the past  20 years may have consumed chicken, they almost always had other environmental exposures (raising birds, visiting `live' markets, slaughtering or preparing poultry, etc.) that make it impossible to single out consumption as the route of infection. 

Recently in Cambodia we've seen a spate of H5N1 cases (and deaths) linked to preparing, cooking, or consuming `sick or dead' poultry. But once again, the exact route of infection remains unknown (see Cambodia: Food Insecurity, Food Safety & H5N1).

All of which brings us to a recent CDC study, published last month in the the Journal Virology, which looks at the available evidence for influenza A infection via the GI tract, and a CDC Summary/Risk Assessment published yesterday.

I've posted links and excerpts from both reports, after which I'll have a bit more.

The (digestive) path less traveled: influenza A virus and the gastrointestinal tract

Trent A. Bullock, Claudia Pappas, Timothy M. Uyeki, Nicole Brock, Troy J. Kieran, Sonja J. Olsen, Todd C. Davis, Terrence M. Tumpey, Taronna R. Maines , Jessica A. Belser  jbelser@cdc.govAuthors Info & Affiliations
https://doi.org/10.1128/mbio.01017-25

PDF/EPUB

ABSTRACT

Influenza A virus (IAV) infection of the respiratory tract can cause both respiratory and non-respiratory symptoms. Gastrointestinal (GI) symptoms such as diarrhea, vomiting, and abdominal pain can occur in persons with seasonal influenza A or novel IAV infections, but the extent to which IAVs can infect and replicate in GI tissues is understudied.

The ongoing outbreak of A(H5N1) IAV in US dairy cattle associated with sporadic human infections has highlighted the potential public health threat posed by the introduction of infectious virus into materials that may be consumed by humans, such as milk. Here, we review epidemiologic reports documenting the frequency of GI complications in humans infected with seasonal and novel IAVs and present laboratory studies supporting the capacity of IAV to replicate in mammalian GI tissues, with an emphasis on A(H5N1) viruses. Studies assessing the ability of IAV to cause mammalian infection following consumption of virus-containing material are also presented.

Collectively, these studies suggest that gastric exposure represents a potential non-respiratory route for A(H5N1) IAVs in mammals that can lead to infection and support that IAV may be detected in mammalian intestinal tissues following multiple exposure routes.

       (Continue . . . )

From the CDC's Website.

Influenza A Viruses May Infect GI Tract and Cause Digestive Symptoms

For Everyone
Sept. 8, 2025

At a glance

A new CDC report highlights the potential for influenza A viruses to cause gastrointestinal (digestive) symptoms in humans and infect mammals through other (non-respiratory) routes.

Background

September 8, 2025 – A new CDC report summarizes data on how influenza A viruses might affect the gastrointestinal (GI) tract of mammals, including people, in the context of the A(H5N1) bird flu outbreak in the United States. A key question has been the potential health threat to people from eating or drinking food or beverages contaminated with avian influenza A(H5N1) viruses, such as contaminated raw (unpasteurized) milk.

While no human infections with A(H5N1) virus have been attributed to consumption of raw cow's milk or products made from raw cow milk, the research summarized in this report shows that some seasonal and novel influenza A viruses may have potential to cause infection of the GI tract.

Additionally, while the risk appears to be low to date, avian influenza A(H5N1) viruses may cause infection in mammals and have potential to cause infection in humans if the digestive tract were exposed to A(H5N1) viruses or virus-contaminated products. This study also notes the need to better understand how influenza A viruses may cause infection through other (non-respiratory) routes, including their potential impact on the GI tract.

(SNIP)

Conclusion and risk assessment

This review of available studies suggests exposure of the digestive system to HPAI A(H5N1) viruses represents a potential non-respiratory route for infection in people and other mammals. There are also unpublished anecdotal reports of raw duck blood consumption as a potential source of A(H5N1) virus infection in a small number of human cases in the past. While the risk of human infection of the GI tract from consuming HPAI A(H5N1) virus-contaminated products is likely low, further investigation is needed to understand how different seasonal and novel influenza A viruses may use the GI tract to possibly infect humans and mammals.

Based on the limited research and information available, we do not know at this time if avian influenza A viruses can be transmitted to people through consumption of raw milk and products (such as cheese) made from raw milk from infected cows. A(H5N1) virus has been found in commercially sold raw milk. Therefore, drinking raw milk or eating products made with raw milk, should be avoided. 

As a reminder, eating uncooked or undercooked poultry or beef, drinking raw (unpasteurized) milk, or consuming other uncooked products made from these animals, can make you sick. Additionally, products made from raw milk, including soft cheese, ice cream, and yogurt, can be contaminated with germs that can cause serious illness, hospitalization, or death. Cooking poultry, eggs, and beef to the appropriate internal temperature kills bacteria and viruses, including avian influenza A viruses. Choosing pasteurized milk and products made with pasteurized milk is an important way to keep you and your family safe. Pasteurization kills bacteria and viruses, like avian influenza A viruses, in milk. Make the best decision for your health and the health of your family by always choosing pasteurized milk and products made with it.

For more information on preventing H5N1 bird flu, including additional guidance on the safe consumption of milk and other dairy products, keep reading: Preventing Bird Flu Infections | Bird Flu | CDC

Governments and the food industry are understandably loath to cast doubts over the safety of the food supply when there is no compelling direct evidence of human infection via that route. 

That said, we've seen governments around the world make great efforts to track down, and remove, suspected HPAI contaminated products from the food supply chain. 

 A few examples include:

• In 2017 tons of H5N8 contaminated poultry products were shipped from a single infected turkey farm in the Rostov region of Russia sparking a massive months-long operation 
  (see Rosselkhoznador: HPAI Contaminated Poultry Shipped To At Least 9 Regions Of Russia).

• The following year (2018) an outbreak of avian H5N8 led Bulgaria To Recall 1 Million Eggs Due To HPAI H5N8.   

• We've also seen contaminated chicken confiscated from shops in Hong Kong (see Hong Kong FEHD Finds Another Shop Selling H5 Contaminated Poultry). 

The USDA (and many other agencies) continue to reassure that `Avian influenza is not transmissible by eating properly prepared poultry, so properly prepared and cooked poultry and eggs are safe to eat.' - but there is a catch.

There are some inherent risks in the slaughtering of live birds and preparation of raw poultry; especially from birds raised at home or purchased from live markets.  PAHO (the Pan-American Health Organization) mentions this on their Avian Influenza landing page:

Transmission

The most common way for the virus to enter a territory is through migratory wild birds. The main risk factor for transmission from birds to humans is direct or indirect contact with infected animals or with environments and surfaces contaminated by feces. Plucking, handling infected poultry carcasses, and preparing poultry for consumption, especially in domestic settings, may also be risk factors.

And last year the WHO published  Interim Guidance to Reduce the Risk of Infection in People Exposed to Avian Influenza Viruses, which lists a number of `risk factors', including:

• keep live poultry in their backyards or homes, or who purchase live birds at markets;

• slaughter, de-feather and/or butcher poultry or other animals at home;

• handle and prepare raw poultry for further cooking and consumption;

While this may seem less of an American or European problem than in Asia or the Middle East, since the arrival of H5N1 in late 2021, the USDA has reported at least 54 outbreaks in live markets across the country (in 6 states; NY, NJ, PA, FL, VA, CA).

 

Additionally, while government agencies `remain confident in the safety of the food supply', the reality is raw milk continues to be sold in most states across the nation (see map at top of blog), and its consumption is common in many other  countries.  

Even though the jury may still be out regarding the transmission of HPAI H5N1 from raw animal products - for me, at least - raw milk, eggs, and steak, chicken or turkey tartare are definitely off my holiday menu list. 

Preprint: Genetic Reassortment and Diversification of Host Specificity Have Driven Evolutionary Trajectories of Lineages of Panzootic H5N1 Influenza

 

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Eight and a half years ago, in a blog titled Sci Reports: Continual Antigenic Diversification Of HPAI H5N1 In China & Around the World, I opened with:

A recurring theme in this blog has been the remarkable spread and growing diversity of (first) HPAI H5N1, followed later by a bevy of related H5Nx viruses (H5N2, H5N3, H5N5, H5N6, H5N8, etc.), all of which have diverged into a dizzying number of lineages, clades, subclades, and genotypes around the globe.

This was written only 5 months after the start of Europe's first major HPAI H5N8 epizootic, which ravaged both wild birds and poultry farms across 29 European nations. 

As we discussed last weekend in H5Nx: Reassort & Repeat, the H5N8 virus underwent a series of crucial reassortment events which increased its host range, improved its ability to be carried asymptomatically by some avian species, and generated several new subtypes, including H5N5, H5N3, and H5N9.

As impressive as these gains in diversity were, they pale in comparison to what we've seen since. In short order these HPAI viruses acquired the ability to persist through the summer in some avian hosts, and to be more easily carried across oceans or continents by other species. 

HPAI H5N8 gave way to an array of new and improved H5N1 viruses, which began their world tour in earnest in 2021, where they encountered many new LPAI avian viruses with which to reassort.

In North America alone we've seen more than 100 new genotypes emerge, while  scores of others have spread across Europe, Asia, and South America. Some are far more successful than others, but each represents a unique evolutionary pathway for the virus to follow. 

Some of these reassortant viruses have developed a greater affinity for infecting mammals; the B3.13 genotype is particularly well suited to infect lactating cows, although the D1.1 genotype has also shown that ability. 

Where all of this leads is anyone's guess, but the sobering reality is we aren't just dealing with a single H5Nx threat, but rather with a large and ever-growing array of H5 viruses, all randomly tossing the genetic dice in ways that could ultimately decide our future. 

All of which brings us to a new preprint with an impressive pedigree - one that looks at how these viruses in both Europe and North America have repeatedly reassorted with local LPAI viruses - producing both host-specialized, and generalist hybrids.  

One example they provide is the Charadriiformes-specialist lineage (EA-2022-BB) - which came about as a result of an reassortment between H5N1 and an LPAI H13 virus common in shorebirds. 

This BB reassortant now circulates almost exclusively in Charadriiformes (shorebirds or waders), with reduced fitness in ducks/chickens.

While many of these reassortants will ultimately fade away - or end up posing no additional risks - host specialization provides our increasingly diverse array of HPAI H5 viruses with new and unpredictable ways to spread and evolve. 

Due to its length (36-pages) and technical nature, I've just posted the abstract and a few excerpts, so follow the link to read the preprint in its entirety.  

I'll have a postscript after the break.  

Genetic reassortment and diversification of host specificity have driven evolutionary trajectories of lineages of panzootic H5N1 influenza

William T Harvey, Rute Maria Pinto, Maryn D Brown, Lu Lu, Jessica L Quantrill, Jiayun Yang, Nunticha Pankaew, Miranda Nel, James Baxter, Alex M P Byrne, Darrell R Kapczynski, Munir Iqbal, Joe James, Ashley C Banyard, Ian Brown, Wendy Barclay, Thomas P Peacock, Paul Digard, Samantha J Lycett
doi: https://doi.org/10.1101/2025.08.20.670882
This article is a preprint and has not been certified by peer review 

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Abstract

Since 2021, subclade 2.3.4.4b A(H5N1) high pathogenicity avian influenza (HPAI) viruses have undergone changes in ecology and epidemiology, causing a panzootic of unprecedented scale in wild and domestic birds with spill-over infections and perceptible transmission in a range of mammalian species, raising concern over zoonotic potential.

HPAI viruses readily exchange gene segments with low pathogenicity avian influenza viruses via reassortment, a mechanism that facilitates pronounced phenotypic change. Observations suggest changes in the seasonality and host range of panzootic viruses, however, data on the role of reassortment in determining such features are limited.

Using phylodynamic approaches, we describe the emergence of the panzootic lineage and using a novel global genotype classification system we describe the subsequent emergence and global structuring of genotypes generated by reassortment.

Focusing on evolutionary dynamics in Europe, we show reassortment has produced high fitness genotypes with enhanced capacity for transmission and further we show such advantages can be host-dependent, contrasting successful generalist genotypes with a specialist lineage (EA-2022-BB) adapted to birds of the order Charadriiformes.

Experimental investigation of NS1-mediated shutoff indicates this Charadriiformes-specialist does not inhibit host cellular gene expression and hamper the defences of more typical hosts such as water- and land-fowl. We attribute this primarily to variation at position 127 of the NS1 protein.

Our results emphasise that reassortment has driven phenotypic change, affected viral fitness, and caused diversification of host specificity and seasonality. Such factors should be considered in studies that seek to identify drivers of HPAI spread and map spillover risk.

Additionally, relaxation of host specialisation, ecological diversification, and potential endemicity in atypical host populations present new reassortment opportunities that could result in further novel phenotypes.

       (SNIP) 

During the ongoing H5N1 panzootic, there is further evidence for host diversification with at least one other instance in which H5N1 viruses have begun to transmit in a novel host population with very limited overlap with the typical community of hosts, the ongoing epizootic in dairy cattle within the USA.

Diversification of host specificity has various interesting evolutionary potential consequences. When viral transmission in different host types becomes increasingly separated, competition between lineages is diminished according to the extent to which lineages cease to transmit within common populations.

With lineages no longer in direct competition for hosts, they can evolve independently in parallel, likely with adaptive changes reflecting the different host associations, increasing the overall genomic diversity of subclade 2.3.4.4b viruses. 

Through independent evolution in different host types, they are exposed to distinct selective pressures and novel reassortment opportunities. Viruses are expected to gain adaptive mutations and may acquire genomic segments from influenza viruses that are endemic to different host types, both of which have the potential to further accentuate differences in host specificity.

It is vital to understand how the evolution of these virus lineages in different fitness landscapes could affect their potential to transmit to humans or other mammals.

       (Continue . . . )

Evidence suggests that the initial spillover of HPAI H5 (genotype B3.13) to Texas cattle occurred several  months before we first learned of it; long enough for the virus to have been spread to multiple states before the first alarm was raised. 

It would take nearly a year before a second genotype (D1.1) would be confirmed in cattle in at least 2 western states (Nevada & Arizona). 

Despite only limited passive surveillance, we've seen hundreds of reports of HPAI H5 in peridomestic mammals (foxes, skunks, mice, cats, and many others) across the United States, Canada, and in Europe. 

Some states appear to be looking harder than others, but even in proactive states these (n=646) reports to the USDA undoubtedly represent just the very tip of the iceberg. 

Since we're not actively looking, we've no idea what other specialist genotypes might be out there in the wild, quietly adapting to a new host. 

While ignorance may be bliss in the short-term, it has a nasty way of catching up with us over the long run.  

Preprint: Intensive Transmission in Wild, Migratory Birds Drove Rapid Geographic Dissemination and Repeated Spillovers of H5N1 into Agriculture in North America

 

Major Global Migratory Flyways – Credit FAO

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In November of 2014 - just one month prior to the first detection of HPAI H5N8 in North America - the debate over the role of migratory birds in the spread of HPAI H5 was still going strong (see Bird Flu Spread: The Flyway Or The Highway?).

Although it had been apparent since the mid-2000s that migratory birds played some role in the spread of HPAI, in 2010 a paper in the British Ecological Society's Journal of Applied Ecology  claimed that the global spread of the H5N1 virus through migratory birds was possible . . . but unlikely.

In January 2014, after South Korea claimed migratory birds carried the newly emerging H5N8 virus in from China, the UN's Scientific Task Force on Avian Influenza and Wild Birds issued a statement: 

“There is currently no evidence that wild birds are the source of this virus and they should be considered victims not vectors ”

and that “. . . focusing attention on wild birds can misdirect critical resources away from effective disease control and result in negative conservation outcomes and loss of biodiversity.”

To be fair, prior to 2016 evidence of long-term carriage of HPAI viruses by migratory birds was fairly limited. But the first diaspora of HPAI H5 from Southeast Asia to Europe and the Middle East in 2006 provided a pretty good indication that migratory birds played at least some role. 

In late 2014 - after H5N8 had been discovered in both Europe and North America - the UN Scientific Task Force on Avian Influenza and Wild Birds released a revised statement which allowed:

Typically, spread of HPAI virus is via contaminated poultry, poultry products and inanimate objects although wild birds may also play a role.

By the summer of 2015, H5N8 had vanished outside of Asia (see PNAS: The Enigma Of Disappearing HPAI H5 In North American Migratory Waterfowl), and to everyone's surprise it did not return the following winter to Europe or North America.

The persistence of HPAI H5 infection in migratory birds was still limited. 

But over the following summer, H5N8 underwent a significant reassortment which appears to have increased its ability to be carried by migratory birds. By fall we were seeing reports of H5N8 turning up in India, then Kazakhstan, and by late October H5N8 had returned to Europe (see FAO Notification Of H5N8 In Hungary). 

Three weeks later, on Nov 19th, in the WHO: Assessment Of Risk Associated With HPAI H5N8, we saw the following description of its remarkable spread.

Since June 2016, countries in both Europe and Asia have detected infections in wild birds and/or domestic poultry with A(H5N8) including Austria, Croatia, Denmark, Germany, Hungary, India, Israel, Netherlands, Poland, Russian Federation and Switzerland. Many of these recent detections were associated with mortality in wild birds.

A chance reassortment (see EID Journal: Reassorted HPAI H5N8 Clade 2.3.4.4. - Germany 2016) had radically changed the virus's behavior; increasing its virulence in some wild birds, while at the same time expanding its avian host range, and giving it unusual environmental persistence through the summer.

Armed with these (and many subsequent) evolutionary changes, today's H5Nx virus is a far cry from the H5N8 virus we were able to contain in 2015 with increased biosecurity and culling.  

But we continue to treat H5N1 as primarily a `poultry problem', when in reality, it now permeates our shared ecosystem; which includes wild birds, poultry, cattle, marine mammals, and even peridomestic mammals.  

All of which brings us to a lengthy (47-page) preprint written by researchers from the Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania on the dramatic shift in HPAI's ecology in North America.

While farm-to-farm spread is still a concern, migratory birds now appear to play the biggest role in the spread of HPAI viruses in North America, which suggests that culling and/or poultry vaccines aren't going to be sufficient to contain the problem.

Complicating matters, HPAI has become widespread in cattle, and may be quietly simmering in other mammalian species (e.g. foxes, skunks, cats, mice, etc.).  

The authors - in addition to calling for enhanced surveillance of wild Anseriformes and shorebirds, and the monitoring backyard flocks as sentinels - warn that:

`Prevention of agricultural outbreaks may now require novel strategies that reduce transmission at the wild bird/agriculture interface.'

Due to its length, I've only posted the abstract, and a short excerpt.  Follow the link to read it in its entirety.   I'll have a brief postscript when you return. 

Intensive transmission in wild, migratory birds drove rapid geographic dissemination and repeated spillovers of H5N1 into agriculture in North America

Lambodhar Damodaran, Anna Jaeger,  Louise H Moncla
doi: https://doi.org/10.1101/2024.12.16.628739

This article is a preprint and has not been certified by peer review 

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Abstract

Since late 2021, a panzootic of highly pathogenic H5N1 avian influenza virus has driven significant morbidity and mortality in wild birds, domestic poultry, and mammals. In North America, infections in novel avian and mammalian species suggest the potential for changing ecology and establishment of new animal reservoirs.

Outbreaks among domestic birds have persisted despite aggressive culling, necessitating a re-examination of how these outbreaks were sparked and maintained. To recover how these viruses were introduced and disseminated in North America, we analyzed 1,818 Hemagglutinin (HA) gene sequences sampled from North American wild birds, domestic birds and mammals from November 2021-September 2023 using Bayesian phylodynamic approaches.

Using HA, we infer that the North American panzootic was driven by ~8 independent introductions into North America via the Atlantic and Pacific Flyways, followed by rapid dissemination westward via wild, migratory birds.

Transmission was primarily driven by Anseriformes, shorebirds, and Galliformes, while species such as songbirds, raptors, and owls mostly acted as dead-end hosts. Unlike the epizootic of 2015, outbreaks in domestic birds were driven by ~46-113 independent introductions from wild birds, with some onward transmission. Backyard birds were infected ~10 days earlier on average than birds in commercial poultry production settings, suggesting that they could act as early warning signals for transmission upticks in a given area.

Our findings support wild birds as an emerging reservoir for HPAI transmission in North America and suggest continuous surveillance of wild Anseriformes and shorebirds as crucial for outbreak inference. Future prevention of agricultural outbreaks may require investment in strategies that reduce transmission at the wild bird/agriculture interface, and investigation of backyard birds as putative early warning signs.

       (SNIP)

Taken together, our findings implicate a critical shift in highly pathogenic avian influenza ecology in North America, with wild birds playing the central role in transmission and dispersal in the 2021-2023 epizootic. Persistent and intensive transmission in wild birds provides an explanation for the rapid cross-continental spread, and continued agricultural outbreaks despite aggressive culling. 

Our results highlight the utility of wild bird surveillance for accurately distinguishing hypotheses of epizootic spread, and suggest continuous surveillance as critical for preventing and dissecting future outbreaks.

Our data underscore that continued establishment of H5N1 in North American wildlife may necessitate a shift in risk management and mitigation, with interventions focused on reducing risk within the context of enzootic circulation in wild birds. 

At the time of writing, outbreaks in dairy cattle highlight the critical importance of modeling the ecological interactions within and between wild birds and domestic production. Future work to effectively model viral evolution and spread hinges critically on effective surveillance across wild and domestic species to capture key transmission pathways across large geographic scales. Ultimately, these data are essential for informing biosecurity, outbreak response, and vaccine strain selection. 

       (Continue . . . ) 

A little over a century ago French Prime Minister Clemenceau is quoted as complaining that ` . . . generals are always preparing to fight the last war', particularly if they had won that war.

The tactics of culling and increased biosecurity that successfully ended the 2015 HPAI epizootic after just 7 months have proved inadequate to halt this new and improved avian virus after more than 43 months. 

While this strongly suggests we need a new playbook, the only thing that appears to be changing is the virus. 

H5Nx: Reassort & Repeat

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In the Northern hemisphere millions of migratory birds spend their summers in their high latitude breeding areas in Alaska, Canada, Siberia, and even the Arctic. More than 200 bird species roost in the Alaskan Arctic Refuge, after which they migrate south each fall via four North American Flyways.

While there, they hatch a new generation of (flu naive) fledglings, while at the same time they mingle with other species - potentially sharing viruses picked up during their  northbound flight the previous spring. 

A 2016 study (see Sci Repts.: Southward Autumn Migration Of Waterfowl Facilitates Transmission Of HPAI H5N1), posits that these viruses may often evolve (or reassort) over the summer, and then are redistributed by migratory birds on their southbound journey the following fall.

And indeed, particularly since 2014, the fall and early winter has seen the introduction of a number of `game-changing' HPAI H5 variants, often the product of reassortment. 

In January 2014, a reassorted HPAI H5N8 virus appeared in South Korea, decimated their poultry industry, and then began a world tour, arriving in North America in less than a year and sparking the first HPAI H5 epizootic in the US and Canada.

While better adapted to long-distance carriage by migratory birds than H5N1, this North American incursion lacked the `legs' to survive the summer, and faded after 8 months (see PNAS: The Enigma Of Disappearing HPAI H5 In North American Migratory Waterfowl).

During the summer of 2016 H5N8 reassorted into a far more robust threat (probably in China or Siberia) - arriving in Europe in October - and sparking their biggest epizootic on record. EID Journal: Reassorted HPAI H5N8 Clade 2.3.4.4. - Germany 2016). 

This new H5N8 was not only deadlier to some bird species, it was more easily carried by others, increasing its range and impact dramatically over the next 6 months.  

We also saw this virus spin off several new subtypes, including H5N5, H5N3, and H5N9. 

Over the winter of 2016-17, this H5N8 virus spread from Europe, into the Middle East, and then Northern Africa. By late spring, 2017, it had crossed the equator and set up shop in South Africa, making it the most successfully disseminated HPAI H5 virus we'd seen.

A European H5N6 briefly appeared in 2018, but H5N8 held on until a new, reassorted H5N1 virus appeared in Europe in 2020, and began to supplant H5N8. 

Unlike previous H5Nx incarnations, this new H5N1 showed an increased affinity for infecting mammals, and a much wider avian host range (see DEFRA: The Unprecedented `Order Shift' In Wild Bird H5N1 Positives In Europe & The UK).

By late 2021 this `new and improved' H5N1 virus had crossed both the Atlantic and Pacific oceans, spreading first to North America, followed by South America, and even the Antarctic.   

The virus has since diversified into more than 100 distinct genotypes in North America alone, and this evolution continues, albeit often outside of our view.  

• In 2023 a new B3.13 genotype emerged that could efficiently infect dairy cattle while mildly infecting dozens of humans

• Last fall we saw 3 new genotypes emerge (D1.1, D1.2, D1.3), with D1.1 producing more severe illness in humans. 

• Last October Canada experienced a multi-farm outbreak of emerging N1 genotype of H5N1 that was  highly resistant to NAI antivirals (carrying the H275Y mutation)

• We continue to see scattered reports of HPAI H5N5 in birds and mammals in Europe & Canada, and occasionally in birds in the United States.

• In Cambodia we've seen a reassorted clade 2.3.2.1e virus infect > 30 people since 2023, while a new triple-reassortant H5N1 clade 2.3.2.1a virus in India has reportedly infected both humans and cats.

These variants likely only represent a small tip of the rapidly expanding H5Nx iceberg. 

As the FAO graphic below illustrates, much of the world simply doesn't report on what is going on with HPAI - either due to limited surveillance capabilities - or due to political or economic concerns. 

Very little of what is actually going on in those remote high latitude roosting areas - or in those parts of the world that aren't closely monitoring (or choose to report) on the panoply of H5Nx viruses - is known, and so we need to be prepared for surprises. 

Past performance obviously doesn't guarantee future results, but HPAI H5Nx appears to be gaining in both diversity and momentum. 

While it is still only mid-August, this year's fall migration has already begun in North America, although it won't peak for several months. 

One of the publicly available tools that we can use to track bird migration comes from the Birdcast.info website, which uses weather radar, and advanced forecasting methods to track birds. 

Dokter, A. M. Year/s of live migration map image. BirdCast, 

live migration map; date and time (most easily accessible from 

image file name/s). Cornell Lab of Ornithology.

https://birdcast.info/migration-tools/migration-forecast-maps.

Screenshot 8/17/25

Over the past 3 weeks we've seen an unexpected summer surge in H5N1 outbreaks at UK poultry farms, which led Defra to increase their risk assessment for some farms this week. 

Making this a good time for poultry producers - and other stakeholders - to seriously consider now how they will deal with the arrival of the next anticipated round of avian flu this fall. 

And any surprises that might bring.

Revisiting the Environmental Persistence and Airborne Spread of HPAI H5

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Not quite two weeks ago, in Preprint: Surveillance on California Dairy Farms Reveals Multiple Sources of H5N1 Transmission, we looked at a (yet-to-be-peer-reviewed) paper that found evidence of extensive environmental (air, water & milking equipment) contamination on HPAI H5 infected dairy farms.

That report - when combined with a recent study (see Dairy Cows Infected with Influenza A(H5N1) Reveals Low Infectious Dose and Transmission Barriers) - would seem to challenge the popular assumption that cow-to-cow transmission of HPAI was primarily due to contaminated milking machines.

Two days ago the Journal Nature took note of the California study:

NATURE BRIEFING
12 August 2025

Daily briefing: Bird flu is ‘everywhere’ on dairy farms

H5N1 avian influenza might be airborne, helping it to spread rapidly in dairy cows

Yesterday UNMC's Global Center for Health Security - which quoted Dr. Richard Webby as saying  “It’s a ridiculously contaminated environment” -  published:

Bird Flu on Dairy Farms May Be Airborne After All

These airborne concerns go far beyond just`exhaled' breath from infected cattle in milking parlors, or `milk spray', as contaminated milk and manure from infected cows must be safely handled and disposed of (along with farm wastewater); none of which are trivial tasks.  

While the USDA has issued biosecurity guidelines (link), the details (and enforcement) are left up to local officials and the producers. 

Any way you slice it, HPAI infected poultry and dairy farms must deal with extensive environmental contamination issues. A concern because we've seen environmental persistence studies showing that - under the right conditions - HPAI H5 can survive for days, weeks, or even months outside of a living host. 

• In 2012's EID Journal: Persistence Of H5N1 In Soil, we looked at several studies that found H5N1 could remain viable on various surfaces, and in different types of soil, for up to 13 days (depending upon temperature, relative humidity, and UV exposure).
• In 2017, researchers showed that - when refrigerated - H5N1 infected poultry could remain infectious for months (see Appl Environ Microbiol: Survival of HPAI H5N1 In Infected Poultry Tissues).

• In 2020 we looked at a study from researchers at the USGS (see Proc. Royal Society B: Influenza A Viruses Remain Viable For Months In Northern Wetlands - USGS), which found long-term (up to 7 months) survival of influenza A viruses in wetlands in both Alaska and Minnesota.

How long avian flu viruses may remain viable, and how far they might be carried (by personnel, vehicles, peridomestic mammals, birds, flies, or even the wind), continues to be poorly understood.

As recently as last February - in Preprint: Genetic & Meteorological Data Supporting Windborne Transmission of HPAI H5N1 - we saw a study that strongly suggested that windborne spread of HPAI H5 virus particles may have spread the virus as far as 8 km between poultry farms in the Czech Republic.

Separation of Farms In Study

We can go back more than a dozen years to find other studies which came to similar conclusions, including. 

• In December of 2012 (see Barnstorming Avian Flu Viruses?) we looked at a study called Genetic data provide evidence for wind-mediated transmission of highly pathogenic avian influenza that found patterns that suggested farm-to-farm spread of the 2003 H7N7 in the Netherlands due to the prevailing wind.

• Another study of the same outbreak, Modelling the Wind-Borne Spread of Highly Pathogenic Avian Influenza Virus between Farms (PloS One 2012), found that windborne transmission could have accounted for up to 24% of the transmission over distances up to 25 km.

• In the spring of 2015 during the North American H5Nx epizootic, the idea of farm-to-farm spread via infected dust was openly discussed by the USDA (see Bird Flu’s Airborne `Division’).

• In 2018, in Frontiers: Two Studies On The Epidemiology of Avian Influenza Viruses, we looked at a study that detected airborne HPAI viruses during the 2016-17 H5N8 epizootic in France, which saw more than 400 farms affected.

• And in 2019, in Nature: Airborne Transmission May Have Played A Role In Spread Of U.S. 2015 HPAI Epizootic, we saw a study that looked at air movement trajectories and viral concentrations during the epizootic and the probability of airborne transmission for the 77 HPAI cases in Iowa. While not definitive, long-range airborne spread was considered plausible.

In 2022's Zoonoses & Public Health: Aerosol Exposure of Live Bird Market Workers to Viable Influenza A/H5N1 and A/H9N2 Viruses, Cambodia, researchers were able to extract viable avian flu viruses from the air in and around live bird markets in Cambodia.

And last January, in Osterholm Podcast: The Potential Environmental (Airborne) Spread of H5N1, Dr. Mike Osterholm discussed the real possibility that the H5N1 virus may be carried by contaminated `dust' from poultry farms, infecting other nearby farms, animals, and potentially even humans.

As we discussed yesterday, a big concern is the potential introduction of HPAI to swine (see Frontiers Vet. Sci (Review): Emerging Threats of HPAI H5N1 Clade 2.3.4.4b in Swine).  Airborne spread between farms is one plausible way that could happen.

Whether H5N1 has the ability to spark a pandemic remains to be seen - but even if it can't - it can still do tremendous damage to agricultural interests and to the economy.  

Which is why a fuller understanding of its abilities (both existing and evolving) is crucial if we hope to avoid a larger crisis. 

EID Journal: Attachment Patterns of Avian Influenza H5 Clade 2.3.4.4b Virus in Respiratory Tracts of Marine Mammals, North Atlantic Ocean

Flu Virus binding to Receptor Cells – Credit CDC

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We've known for over 4 decades that marine mammals (seals, whales, dolphins, etc.) are susceptible to influenza A viruses (see 1984's Are seals frequently infected with avian influenza viruses? by Webster et al.), and over the past 20 years have looked a number of unusual mortality events (UMEs). 

• In November of 2011 a die off of seals in New England that was eventually tied to an H3N8 avian Flu Virus. 2012's mBio: A Mammalian Adapted H3N8 In Seals, presented evidence that this virus had recently adapted to better bind to alpha 2,6 receptor cells, the type found in the human upper respiratory tract.

• A large outbreak was reported from northern Europe (mostly Denmark and Germany & Sweden) in 2014, when as many as 3,000 harbor seals reportedly died from avian H10N7 (see Avian H10N7 Linked To Dead European Seals), prompting warnings to the public not to touch seals.
• In 2017, during the HPAI H5N8 epizootic in Europe, that emerging subtype (clade 2.3.4.4.B) was found in Grey seals in the Baltic Sea (see EID Journal: Highly Pathogenic Avian Influenza A(H5N8) Virus in Gray Seals, Baltic Sea).

While some outbreaks have likely gone unreported, it wasn't until 2017 that an HPAI H5 virus (H5N8) was detected in marine mammals (see above). The big surge, however, began in 2020, after the changeover from H5N8 to H5N1:

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

UK: HAIRS Risk Assessment On Avian Flu In Seals (2022)

Quebec: Seal Deaths Linked To Avian H5N1

Chile: SERNAPESCA Reports A Record Number of Marine Strandings In 1st Quarter of 2023

EID Journal: Mass Mortality of Sea Lions Caused by HPAI A(H5N1) Virus (Peru)

Preprint: Massive outbreak of Influenza A H5N1 in elephant seals at Peninsula Valdes, Argentina: increased evidence for mammal-to-mammal transmission

Not only have tens of thousands of marine mammals died from HPAI H5 over the past 5 years, there is growing evidence that some species can transmit the virus from mammal-to-mammal (see Nature Comms: Cross-species and mammal-to-mammal transmission of clade 2.3.4.4b HPAI A/H5N1 with PB2 adaptations).

Since 2020 we've seen HPAI H5N1 dramatically increase both its geographic and (avian & mammalian) host range, as well as producing increased neurological manifestations (see Cell: The Neuropathogenesis of HPAI H5Nx Viruses in Mammalian Species Including Humans) in some hosts.

Simply put, the H5Nx virus of today is a far cry from the H5Nx of 2005, or even 2019. And those changes are likely to continue. 

Today we've a research paper published in the EID Journal which suggest that these changes may be linked to changing viral cell tropism favoring lower respiratory tracts in some mammals.  

Among their key findings:

• Researcher found both the 2005 and 2022 H5N1 viruses attached readily to upper respiratory tract tissues in seals
• But the 2022 clade 2.3.4.4b virus showed significantly increased affinity for  lower respiratory tract tissues as well 
• Additionally, seals showed greater susceptibility than cetaceans (porpoises and dolphins)

Due to its length, I've only posted the abstract a few excerpts. Follow the link to read it in its entirety.  I'll have a bit more after the break. 

Attachment Patterns of Avian Influenza H5 Clade 2.3.4.4b Virus in Respiratory Tracts of Marine Mammals, North Atlantic Ocean

Syriam Sooksawasdi Na Ayudhya1, Lonneke Leijten, Willemijn F. Rijnink, Monique I. Spronken, Thijs Kuiken, Lisa Bauer2, and Debby van Riel2

Abstract

Highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus infections have caused substantial mortality events in marine mammals in recent years. We hypothesized that the high number of infections and disease severity could be related to cell tropism in respiratory tracts. Therefore, we examined the attachment pattern of an H5N1 clade 2.3.4.4b virus (H52022) as a measure for cell tropism in the respiratory tracts of harbor seals, gray seals, harbor porpoises, and bottlenose dolphins and compared it with an H5N1 clade 2.1.3.2 virus (H52005) and a human seasonal H3N2 virus using virus histochemistry.

Both H5 viruses attached abundantly to olfactory and respiratory mucosa in the upper respiratory tract of both seal species. H52022 attached more abundantly than H52005 to epithelial cells in the lower respiratory tract of all species. The observed attachment possibly explains the susceptibility of marine mammal species for recent H5N1 viruses and the observed development of severe disease.

(SNIP)

The ability of HPAI H5N1 clade 2.3.4.4b viruses to infect and cause severe disease in a broad range of mammal species has not been previously observed with other avian influenza A viruses (3,34).

The attachment pattern in the respiratory tract of marine mammals of H5N1 clade 2.3.4.4b virus, and whether that pattern differs from the attachment pattern of previously circulating H5 viruses from different clades, is unknown. Therefore, we compared the attachment pattern of a 2022 H5N1 clade 2.3.4.4b virus, a 2005 H5N1 clade 2.1.3.2 virus, and a seasonal human H3N2 virus in the respiratory tracts of marine mammals commonly found in the North Atlantic Ocean: harbor seals, gray seals, harbor porpoises, and bottlenose dolphins.

       (SNIP)

Discussion

We describe the attachment patterns of HPAI H5N1 viruses in the respiratory tracts of common North Atlantic marine mammals. Our study revealed that avian H5 viruses attach abundantly to the upper respiratory tract of harbor seals and gray seals. In the lower respiratory tract of harbor seals, gray seals, and harbor porpoises, the recent H5N1 clade 2.3.4.4b virus attaches more abundantly than an H5N1 clade 2.1.3.2 virus from 2005.

(SNIP)

Several studies have shown that recent H5N1 clade 2.3.4.4b viruses, including bovine isolates, preferentially bind to α2,3-linked sialic acid receptors (41,45–47). The variability in attachment between the 2 H5N1 virus clades in our study are therefore likely not the result of a receptor switch to 2,6-linked sialic acid but potentially because of the amino acid differences in or close to the receptor-binding site, known to affect receptor specificity or affinity. However, the exact role of the individual amino acid positions remains to be investigated

Both HPAI H5N1 viruses (either of clade 2.3.4.4b or clade 2.1.3.2) and H3N2 virus attach to olfactory mucosa in the nasal cavity of gray and harbor seals. Neurologic complications are regularly observed in marine mammals infected with H5 viruses, and virus can be detected in high titers in the brain (19,21,23,24,28).

How H5 viruses enter the central nervous system remains unclear, but observations suggest that the viruses can enter the central nervous system via the olfactory nerve in seals, as observed in experimentally inoculated ferrets (48–50). However, HPAI H5N1 viruses can also invade the central nervous system in ceteceans, which lack a olfactory mucosa, so neuroinvasion likely could also occur via other cranial nerves or the hematogenous route (28).

In conclusion, our study highlights changes in the attachment pattern of a recent HPAI H5N1 clade 2.3.4.4b virus compared with H5N1 clade 2.1.3.2 virus from 2005 in the respiratory tracts of 4 marine mammal species that could lead to more efficient transmission and more severe disease.

That finding, together with the recent increase in HPAI H5N1–associated deaths in marine mammals worldwide, emphasizes the need for increased avian influenza surveillance and research in such marine mammal species to limit illness and deaths and help protect both animal and human health.

Dr. Sooksawasdi Na Ayudhya is an instructor and researcher at the Faculty of Veterinary Science, Prince of Songkla, Songkhla, Thailand. Her main interests are pathogenesis and molecular epidemiology of viral infectious diseases and viral emerging infectious diseases in humans and animals.

       (Continue . . . )


Not so very long ago conventional wisdom held that for HPAI H5N1 to pose a genuine human pandemic threat, it would need to change its preference for avian α2,3-linked receptor cells to mammalian α2,6-linked receptor cells.

And while that may still be true, there are hints in this study that other genetic changes in (or near) the RBD (Receptor Binding Domain) of the virus may enable avian α2,3 binding viruses to better infect mammals.

We've seen other examples of `permissive mutations' that can counteract the effects of existing genetic traits (see Virus Research: A 15-year Study of Neuraminidase Mutations and the Increasing of S247N Mutation in Spain). 

Today's report is reminder that the HPAI H5 virus of today is not the same H5N1 virus that threatened - but failed - to produce a pandemic 20 years ago. 

If the past 18 months have taught us anything, it is that the HPAI H5Nx virus is rapidly evolving on multiple fronts - and while that doesn't guarantee a more formidable virus in the future - the trajectory we are seeing is far from reassuring. 

Svalbard: HPAI H5N5 Detected In Arctic Foxes

Location of Svalbard in the Arctic Ocean

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While H5N1 clade 2.3.4.4b is currently the dominant HPAI strain around the globe, older clades (2.3.2.1a in India and 2.3.2.1e in Cambodia) continue to circulate and occasionally spill over into humans. 

Additionally, China has reported > 90 human infections with a different subtype; H5N6 (clade 2.3.4.4x), and we've been closely watching the spread of HPAI H5N5 in both Eastern Canada, and Northern Europe. 

Credit: Multiple transatlantic incursions of highly pathogenic avian influenza clade 2.3.4.4b A(H5N5) virus into North America and spillover to mammals

In the summer of 2022, the Norwegian Veterinary Institute reported both H5N1 and H5N5 for the first time in wild birds on Svalbard, which lies above the Arctic circle (see More HPAI (H5N5 & H5N1) Detected In Arctic (Svalbard). 

Since then we've been tracking a small - but growing - number of spillovers of H5N5 to mammals in both Europe and Canada, including seals in the UK, domestic cats in Iceland, and raccoons (and other small mammals) in Canada.

Last summer, in Cell Reports: Multiple Transatlantic Incursions of HPAI clade 2.3.4.4b A(H5N5) Virus into North America and Spillover to Mammals, researchers reported finding the mammalian adaptive E627K mutation in a number of samples.

While HPAI H5N5 doesn't currently appear likely to overtake or supplant H5N1, we've seen several abrupt dominant subtype changes (H1N1-> H5N8 -> H5N1) occur over the past 20 years.

With influenza, the only constant is change. 

All of which brings us to the following (translated) report, published yesterday by the Norwegian Veterinary Institute, which reports on H5N5 infections in Arctic foxes on Svalbard. 

Avian influenza detected in arctic foxes in Svalbard
Published 04.08.2025

The Norwegian Veterinary Institute has detected highly pathogenic avian influenza virus in four arctic fox pups from an area near the Russian settlement of Barentsburg on Svalbard. This is the first time the virus has been detected in arctic foxes in Norway.


Arctic foxes from Svalbard have been studied at the Norwegian Veterinary Institute. Photo: Ingunn Ruud, Norwegian Veterinary Institute

At the end of July 2025, the Governor of Svalbard received a report of several sick mountain foxes near the Russian settlement of Barentsburg. Three sick pups were initially observed, and two of these were euthanized for animal welfare reasons. Due to the proximity to Barentsburg and increased rabies vigilance, the rest of the litter was euthanized. Of the three remaining pups, one was sick. In addition, three adult mountain foxes near the den were euthanized.

H5N5 is circulating in the highlands

The arctic foxes were sent to the Veterinary Institute in Ås for testing for rabies and avian influenza viruses. The analyses showed that all the foxes were negative for rabies virus, while four arctic fox pups were positive for highly pathogenic avian influenza virus. The virus detected is of the subtype H5N5, a subtype that circulates in the high north and has caused cases of disease in both wild birds and mammals in the Nordic countries, Iceland and the United Kingdom in recent years. The subtype was detected in a walrus in Svalbard in 2023.

On the mainland, the H5N5 subtype has been detected in Nordland and Finnmark in June and July, with the last case being in a black-backed deer in Vadsø at the end of July. There have been no detections of H5N5 in mammals in Norway this year, but the subtype was detected in otters in Tromsø in October and December 2024, and in red foxes in Kvænangen in February 2024.

Infection pressure when eating infected birds

Arctic foxes can become infected with avian influenza through direct contact with sick or dead animals. Foxes are scavengers that are exposed to high infection pressure when they eat infected birds. Studies of red foxes on the mainland indicate that foxes do not have the ability to infect each other. Whole-genome sequencing of the viruses from arctic fox pups will be carried out to investigate whether there are signs of mammalian adaptation in the viruses.

May resemble rabies infection

Highly pathogenic avian influenza virus can cause clinical signs of brain disease and are similar to those seen in rabies infection. Neurological signs such as circling gait, tilted head position, paralysis and decreased shyness towards humans are common. Both highly pathogenic avian influenza and rabies are serious diseases that can infect humans, and it is therefore important to avoid contact with sick animals. If the population of Svalbard observes sick animals with or without neurological symptoms, it is important that the findings are reported to the Governor.

Report any suspicions to the Norwegian Food Safety Authority

If there is suspicion of infection with avian influenza in birds and other animals, the Norwegian Food Safety Authority must be notified . The Veterinary Institute is the national reference laboratory for avian influenza and has PCR diagnostics and whole genome sequencing available for the detection and characterization of avian influenza viruses.

Privately practicing veterinarians: Avian influenza in mammals | Norwegian Food Safety Authority

Although HPAI H5 is primarily regarded as a respiratory virus, two years ago (see Cell: The Neuropathogenesis of HPAI H5Nx Viruses in Mammalian Species Including Humans) researchers warned that ` . . . highly pathogenic avian influenza (HPAI) H5Nx viruses can cause neurological complications in many mammalian species, including humans'.

While clinical details on cases are often limited, we've already seen a small number of human infections reported as presenting with severe neurological involvement, including:

Vietnam: Ho Chi Minh DOH Reports A Rare H5N1 Encephalitis Case In a Child

Clinical Features of the First Critical Case of Acute Encephalitis Caused by Avian Influenza A (H5N6) Virus

CJ ID & MM: Case Study Of A Neurotropic H5N1 Infection - Canada

A sobering reminder that the next global health crisis may not play out like the last one, or the ones that came before.  As epidemiologists like to say:

“If you’ve seen one pandemic . . . you’ve seen one pandemic.”