Canada & U.S. Report Early Fall Uptick In H5N1 Outbreaks In Poultry

 

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In 2024, it wasn't until mid-October that we began seeing a significant uptick in North American poultry outbreaks due to the HPAI H5 virus. The following screenshot from the USDA (taken 10/17/24) shows only one outbreak in U.S. commercial poultry in the month of September. 

By contrast, in the first 11 days of September 2025, the USDA has already confirmed 7 commercial (and 4 backyard) outbreaks. 

Similarly, last year Canada went a full 6 months - (April 10th - Oct 21st) without reporting an HPAI outbreak in poultry (see screenshot below). 

After a summer hiatus - this time of just under 4 months - this week Canada's CFIA this week is reporting 3 HPAI outbreaks in Alberta, nearly 6 weeks earlier than last year. 

It is also notable that this summer the UK, and more recently Spain, have reported unusually high avian flu activity (see UK Defra: Heightened Avian Influenza Risk Warning Issued to Bird Keepers and Gamebird Rearers).

As we discussed at length last month in H5Nx: Reassort & Repeat, 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 (see map at top of blog), after which they migrate south each fall via four North American Flyways.

During their stay, they hatch a new generation of (flu naive) fledglings while mingling with other species, potentially sharing avian viruses picked up the previous spring (see 2016's Sci Repts.: Southward Autumn Migration Of Waterfowl Facilitates Transmission Of HPAI H5N1).

These factors can promote the creation and spread of new reassortants (genetic hybrids). While most are genetic failures - and unable to compete with existing strains - every once in a while a `new and improved' virus appears. 

Two years ago (fall/winter 2023) we saw a new H5N1 B3.13 genotype emerge that could efficiently infect dairy cattle, while mildly infecting dozens of humans. Although not as well adapted to poultry, some spillovers were reported. 

Last fall (2024), we saw 4 new genotypes emerge (D1.1, D1.2, D1.3), with D1.1 producing more severe illness in humans, while Canada experienced a multi-farm outbreak of emerging N1 genotype that was highly resistant to NAI antivirals. 

Although past performance is no guarantee of future results, since HPAI H5N1 arrived in North America in 2021, more than 100 genetically distinct genotypes have emerged.  

Another thing we are watching is the slow incursion of HPAI H5N5 - which has been reported in both Canada and Northern Europe (see Svalbard: HPAI H5N5 Detected In Arctic Foxes) - into the United States.

The USDA currently only lists 23 detections (in wild birds) across 4 states (primarily Massachusetts, along with Connecticut, Maine, and Michigan), but given the limits of surveillance and testing, this likely underrepresents its range and impact. 

Given the surge of reports over the past few weeks, it is not too early for poultry producers, dairy farmers  - and other stakeholders - to seriously consider now how they will deal with the likely return of avian flu this fall. 

And any surprises that it might bring.

MMWR: Influenza-Associated Hospitalizations During a High Severity Season (United States, 2024–25)

 

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As the CDC estimate for our most recent flu season (above) illustrates, our ability to identify, and track, influenza-related hospitalizations and deaths is limited.  The CDC estimates somewhere between 27,000 and 130,000 deaths since October of 2024. 

For the past 15 years the CDC has estimated the burden of seasonal flu using a mathematical model that uses data collected through the Influenza Hospitalization Surveillance Network (FluSurv-NET); a network that covers only about 9% of the U.S. population. 

Complicating matters - flu-related deaths are not considered `reportable'  unless they occur in pediatric patients - and even then only some percentage of deaths are likely captured. 

In the aftermath of the H1N1 pandemic of 2009, the CDC estimated the number of pediatric deaths in the United States likely ranged from 910 to 1880, or anywhere from 3 to 6 times higher than reported.

Which suggests that this year's record setting number of pediatric seasonal-flu related deaths is also likely an undercount. 

While the exact numbers are hard to pin down, the 2024-2025 flu season now ranks as the most impactful flu season since 2010, with the highest estimated hospitalization rate in more than a decade.

Yesterday the CDC published a late-season recap in their weekly MMWR.  I've reproduced some excerpts (follow the link to read it in its entirety).  I'll have more after the break.

Influenza-Associated Hospitalizations During a High Severity Season — Influenza Hospitalization Surveillance Network, United States, 2024–25 Influenza Season


Weekly / September 11, 2025 / 74(34);529–537
Print

Alissa O’Halloran, MSPH1; Jennifer Whitmill Habeck, MPH1,2; Matthew Gilmer, MS1,2; Ryan Threlkel, MPH1; Shua J. Chai, MD3,4; Brenna Hall, MPH3; Isaac Armistead, MD5; Nisha B. Alden, MPH5; James Meek, MPH6; Kimberly Yousey-Hindes, MPH6; Kyle P. Openo, DrPH7,8; Lucy S. Witt, MD7,8; Maya L. Monroe, MPH9; Patricia A. Ryan, MS9; Lauren Leegwater, MPH10; Sue Kim, MPH10; Melissa McMahon, PhD11; Ruth Lynfield, MD11; Khalil Harbi, MSPH12; Murtada Khalifa, MBBS13; Caroline McCahon13; Grant Barney, MPH14; Bridget J. Anderson, PhD14; Christina B. Felsen, MPH15; Brenda L. Tesini, MD15; Nancy E. Moran, DVM16; Denise Ingabire-Smith, MPH16; Melissa Sutton, MD17; M. Andraya Hendrick, MPH17; William Schaffner, MD18; H. Keipp Talbot, MD18; Andrea George, MPH19; Hafsa Zahid, MPH19; Shikha Garg, MD1; Catherine H. Bozio, PhD1 (VIEW AUTHOR AFFILIATIONS)View suggested citation

Summary

What is already known about this topic?

Seasonal influenza causes substantial annual U.S. morbidity and mortality.

What is added by this report?

Among a surveillance sample of the U.S. population, 2024–25 was a high severity influenza season. The cumulative influenza-associated hospitalization rate was the highest since 2010–11. During the 2024–25 season, the percentages of patients admitted to an intensive care unit (16.8%) and who received invasive mechanical ventilation (6.1%) were similar to past seasons’ estimates. Approximately one third of hospitalized patients were vaccinated. Children aged 5–17 years were the lowest percentage of hospitalized patients receiving antiviral treatment (61.6%).

What are the implications for public health practice?

All persons aged ≥6 months should receive an annual seasonal influenza vaccine. All hospitalized patients with suspected or confirmed influenza should receive timely antiviral treatment to reduce the risk for influenza-associated complications.
 

Full Issue PDF

Abstract

The U.S. 2024–25 influenza season was a high-severity season characterized by co-circulation of influenza A(H1N1)pdm09 and A(H3N2) viruses. Data from the Influenza Hospitalization Surveillance Network covering 9% of the U.S. population, were analyzed to compare laboratory-confirmed influenza-associated hospitalization rates and patient clinical characteristics from the 2024–25 season with data from past seasons.

Based on preliminary data from influenza-associated hospital admissions from October 1, 2024, through April 30, 2025, the cumulative influenza-associated hospitalization rate (127.1 influenza-associated hospitalizations per 100,000 population) had surpassed all end-of-season rates during the period beginning with the 2010–11 season.

Cumulative 2024–25 season rates were highest among persons aged ≥75 years (598.8). Across age groups, hospitalization rates during the 2024–25 season were 1.8 to 2.8 times higher than median historical rates during the period beginning with the 2010–11 season.

Among hospitalized patients, 32.4% had received an influenza vaccine, and 84.8% received antiviral treatment, though children and adolescents aged 5–17 years had the lowest proportion of antiviral receipt (61.6%). Similar to past seasons, most patients hospitalized with influenza during the 2024–25 season (89.1%) had one or more underlying medical conditions, 16.8% were admitted to an intensive care unit, 6.1% received invasive mechanical ventilation, and 3.0% died in hospital.

Seasonal influenza viruses can cause severe disease, particularly among persons who are at higher risk for complications. CDC recommends that all persons aged ≥6 months who do not have contraindications receive an annual influenza vaccine and that all hospitalized patients with influenza receive timely antiviral treatment to reduce the risk for complications.

       (SNIP)

High rates observed during the 2024–25 season could have been driven by recent lower influenza vaccination coverage in the general population (Weekly Flu Vaccination Dashboard | CDC), as well as virus characteristics. The distribution of 2024–25 influenza virus A subtypes might partially explain why, in contrast to other age groups, rates among persons aged ≥75 years were not the highest compared with past seasons. 

Since persons aged ≥75 years retain immunologic protection against A(H1) viruses from early childhood exposures, they have historically experienced more severe illness and death in A(H3N2)-predominant seasons (4). In 2017–18, the last season classified as highly severe for all age groups, circulating influenza A viruses were predominantly A(H3N2) (84%), whereas in 2024–25, both A(H3N2) and A(H1N1) viruses co-circulated equally (FluView Weekly Influenza Surveillance Report | CDC). 

Annual influenza vaccination for persons aged ≥6 months and early initiation of antiviral treatment for patients with influenza who are at higher risk for complications can help prevent adverse outcomes (5,6). Nonpharmacologic measures, such as hand washing, might also prevent transmission (6,7).

        (Continue . .  ) 

Seasonal flu is notoriously unpredictable - and a mild epidemic is always possible - but there are a few reasons to be concerned about the upcoming respiratory season.

• First, Australia has reported an unusually severe flu season (link), which Dr. Ian Mackay has chronicled in his Virology Down Under blog (see A Flunami in July). 

• Second, two weeks ago Denmark reported An Unusually Early Major Outbreak of Influenza A (H1N1),which displayed unspecified `unique changes'. 

• Third, the UK has seen a steady increase in flu severity over the past couple of seasons, with 2023 being more severe than 2022, and 2024 being more severe than 2023. 
• Fourth, we've been following reports of a slow rise in antiviral resistant flu viruses for the past couple of years (see EID Journal: Multicountry Spread of Influenza A(H1N1)pdm09 Viruses with Reduced Oseltamivir Inhibition, May 2023–February 2024).

All good reasons to get the seasonal flu shot this fall. 

But to these, we can add one more; concerns over possible coinfection with seasonal flu and H5N1 (see Preprint: Intelligent Prediction & Biological Validation of the High Reassortment Potential of Avian H5N1 and Human H3N2 Influenza Viruses).

 

Antigenic `Shift' or Reassortment

While the most obvious concern is that a farm worker or veterinarian might be exposed to HPAI H5 (or swine flu) while concurrently infected with seasonal flu, over the past year we've seen a handful of non-farm related H5 infections in the U.S. and Canada. 

It isn't just a theoretical concern; twice in my lifetime (1957 & 1968) avian flu viruses have done precisely that: reassorted with a seasonal flu virus and launched a human pandemic.

• The first (1957) was H2N2, which according to the CDC `. . . was comprised of three different genes from an H2N2 virus that originated from an avian influenza A virus, including the H2 hemagglutinin and the N2 neuraminidase genes.'

• In 1968 an avian H3N2 virus emerged (a reassortment of 2 genes from a low path avian influenza H3 virus, and 6 genes from H2N2) which supplanted H2N2 - killed more than a million people during its first year - and continues to spark yearly epidemics more than 50 years later.

While increased uptake of the flu vaccine isn't guaranteed to prevent this sort of untoward event, it should help reduce the chances.

Which is why sometime in the next 30 days I'll roll up my sleeve to get my 20th seasonal flu shot in as many years. In all of that time I've only caught the flu once (summer 2009), before the pandemic H1N1 vaccine was released.

While I recognize it probably only provides my age group with 30%-40% protection, given the long list of things that can go wrong during or following flu infection, I'll take whatever advantage I can get.

And if, perchance, it prevents a pandemic-inducing reassortment with HPAI H5 (not that we'll ever know), so much the better.

Preprint: Infection of Ratites with Clade 2.3.4.4b HPAIV H5N1: Potential Implications for Zoonotic Risk

 
Rhea - Credit Wikipedia

#18,869

As the months-long legal battle (see CFIA Update On H5N1 In a B.C. Ostrich Farm) over the fate of roughly 400 ostriches in British Columbia continues, overnight the Canadian Press reported the CFIA recently filed an affidavit with the courts calling the strain isolated in B.C. `among the most virulent' ever tested at Canada's National Microbiology Laboratory.

Over the years we've seen growing evidence that Ratites (large flightless birds which include Ostriches, Reas, and Emus) are particularly susceptible to avian flu viruses, including this early (Dec. 2007) report describing the emergency culling of 36K ostriches in Riyadh, Saudi Arabia for HPAI H5N1.  

We've seen reports of both HPAI and LPAI AIV viruses in Ratites, with many displaying mammalian adaptations. Including 2016's Susceptibility and Status of Avian Influenza in Ostriches, which looked at > 70 outbreaks in South Africa, and included the following tidbit:

Seventeen of 27 (63%) ostrich viruses contained the polymerase basic 2 (PB2) E627K marker, and 2 of the ostrich isolates that lacked E627K contained the compensatory Q591K mutation, whereas a third virus had a D701N mutation. 

PB2-627K is often associated with enhanced replication and pathogenicity in mammals, and is one of the most important mutations that H5Nx is thought to need in order to spread more efficiently in mammals  (see A rapid review of the avian influenza PB2 E627K mutation in human infection studies).

There are others, of course (PB2 D701N, PB2 Q591K, HA Q226L, etc.) - each providing the virus with unique advantages - but if you want to kickstart mammalian transmission, PB2-E627K would be at or near the top of your list.

Luckily, these mammalian adaptations tend to exact a `fitness penalty' in avian hosts, making their spread via birds far less likely.  An exception, however, is an emerging PB2-627V, which appears to be making inroads in Chinese poultry.

All of which brings us to the above mentioned preprint, where researchers from the UK's APHA investigated a (Dec 2024) outbreak among captive Rheas (n=5) infected with HPAI H5N1 (clade 2.3.4.4b) genotype DI.2. in the UK. 

As we've seen previously, the PB2-E627K mutation was observed in most of the sequenced samples from the Rheas, with one containing both 627E (in the brain) and 627K (in the oropharynx) suggesting within-host viral diversity.

Unexpectedly, some of the infected co-housed chickens were also found to have the 627K mutation, presumably acquired from the Rheas.  As the authors point out:

Understanding the extent that avian species can maintain mammalian adaptative mutations, is crucial for determine AIV evolution and zoonotic risk.

This study also makes note of the unexpected widespread strong vascular tropism of the HPAI H5N1 virus in Rheas, and its ability to cause severe multifocal necrotising inflammation.

I've reproduced the abstract, and some excerpts from the preprint, but you'll want to follow the link to read it in its entirety.   

Infection of ratites with clade 2.3.4.4b HPAIV H5N1: Potential implications for zoonotic risk
Holly A. Coombes, Jacob Terrey, Audra-Lynne Schlachter, Phoebe McCarter, Isabella Regina, Richard Hepple, Natalie McGinn, James Seekings, Jayne Cooper, Benjamin Clifton,  Benjamin C. Mollett, Marco Falchieri, Alejandro Nunez, Scott M. Reid,  Joe James,  Ashley C. Banyard
doi: https://doi.org/10.1101/2025.09.08.674895
This article is a preprint and has not been certified by peer review 

Preview PDF

Abstract

We detected H5N1 high pathogenicity avian influenza in captive Greater Rhea (Rhea americana). Viral genetic analysis revealed the mammalian associated PB2-E627K mutation, indicating selection of mammalian-relevant mutations in ratites. Pathologic investigation of available tissues demonstrated severe multifocal necrotising inflammation, and a strong vasculotropism.

       (SNIP)

To effectively replicate and transmit in mammalian cells, AIVs must overcome multiple host barriers. However, adaptation of AIVs to different avian hosts and variation in host factors is still poorly understood. A key viral adaptation for successful mammalian replication is restored binding of the viral polymerase to host factor acidic nuclear phosphoprotein 32 family member A(ANP32A) [9].

 An amino acid change at residue 627 in the PB2 protein, from a glutamate (E) to a lysine (K) is frequently found in mammalian viral sequences [10]. Ratites, along with mammals, lack a 33 amino acid insertion in their ANP32A receptor, typically seen in other avian species, leading to a weaker interaction between the receptor and the viral polymerase [9].

The 627K mutation appears to compensate for this weakened interaction, restoring viral polymerase activity and replication in mammalian cell lines (ref for cell lines) [9]. This may explain why ratites appear to select for 627K mutations, as demonstrated by this study. 

Epidemiological and clinical data suggests viral transmission from rheas to co-located chickens, supported by the 627K mutation being present in most of the chicken viral sequences. Although exact transmission chains could not be determined from the sequence data, the persistence of 627K in chickens, despite their avian-like ANP32A, indicates potential  maintenance of mammalian adaptive mutations in avian species.

Understanding the extent that avian species can maintain mammalian adaptative mutations, is crucial for determine AIV evolution and zoonotic risk. One rhea contained both 627E and 627K viral variants, suggesting within-host viral diversity and viral trophism.

This is the first description of pathologic changes in ratites infected with HPAIV H5N1.

Virus induced endothelial damage, vascular inflammation and thrombosis is a known consequence of HPAI H5N1 infection, previously described in cats [11], wild carnivores [12], wild birds [13] and mice [14] in the brain, lungs and eyes.

However, the frequent leukocytoclastic inflammation observed in the walls of small to medium vessels, the resultant necrotising inflammation and the abundance of viral antigen detected in most tissues sampled in these birds was unexpected. Viral characteristics (e.g. viral strain, infection route and dose) or host specific factors such as species, age, duration of infection, concomitant disease and immune status likely influenced lesion severity and antigen expression [15].

Despite a limited selection of tissues and small sample size, findings suggest a widespread strong vascular tropism in this species.

Overall, the viral changes detected in the rhea demonstrated early adaptive events following infection of a novel host, including a key viral adaptation that is often associated with increased zoonotic risk. Assessment of viral evolution in microenvironments where unrelated species are co-housed can provide important evidence regarding adaptation to novel hosts.

        (Continue . . . )

A reminder that - given enough time and opportunities - even an old virus can learn new tricks.  

CDC: COCA Call Today on Measles Cases And Outbreaks In the United States

 
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As the CDC graphic (below) illustrates, 2025 has been a particularly bad year for measles in the United States; the worst in the 21st century.

Once considered eliminated in the United States, in recent years we've seen an increase in cases fueled by falling childhood vaccination rates (see CDC Map below).

When it comes to transmissibility in an unvaccinated population, measles is about as efficient as a virus gets. It's R0 (pronounced R-nought) or Basic Reproductive Number, is usually cited as 16 or higher, while a pandemic flu might only have an R0 of 2 to 3. 

Measles also has a long incubation period (2-3 weeks), and a person may be contagious for up to 4 days before symptoms appear, aiding in its transmissibility.

While some cling to the idea that what doesn't kill you, makes you stronger we've recently learned that measles infection appears to dramatically reduce your immune system's ability to fight other pathogens; even those that you had previously developed antibodies against. 

It's called Immune Amnesia - where the patient's T cells and B cells are greatly reduced - and it can last for several years.  A few studies include:

Measles virus infection diminishes preexisting antibodies that offer protection from other pathogens

Immune amnesia induced by measles and its effects on concurrent epidemics

Measles vaccination and reduced child mortality: Prevention of immune amnesia or beneficial non-specific effects of measles vaccine?

Last month the CDC scheduled a COCA call on this topic, but postponed it until today.  These presentations are often technical, and are of greatest interest to clinicians and healthcare providers, but are also archived and made available to the general public.

You'll find details on attending today's presentation below.

Clinician Update on Measles Cases and Outbreaks in the United States

Health Care Providers
Sept. 11, 2025

At a glance

During this COCA Call, presenters will discuss the current epidemiology of measles in the United States and address the most common questions from clinicians about preventing, identifying, and testing for measles. Presenters will also summarize measles, mumps, and rubella (MMR) vaccination recommendations and considerations.

Overview

This year, record-breaking numbers of measles cases and outbreaks have been reported in the United States, despite measles being declared eliminated in 2000. While the risk of widespread measles remains low for the general population due to high population-level immunity, measles importations continue to occur. Outbreaks of three or more related cases continue to be reported, especially in communities with low vaccination coverage. Healthcare providers should remain vigilant to rapidly recognize measles and take steps to mitigate its spread.

During this COCA Call, presenters will discuss the current epidemiology of measles in the United States and address the most common questions from clinicians about preventing, identifying, and testing for measles. Presenters will also summarize measles, mumps, and rubella (MMR) vaccination recommendations and considerations.

Webinar

Date: Thursday, September 11, 2025

Time: 2:00–3:00 P.M. ET

A few minutes before the webinar begins, please click here to join.

Webinar ID: 862 4856 3488

Passcode: 745762

Or

Dial in using phone one-tap:

+16465588656,,86248563488#,,,,*745762#

+16469313860,,86248563488#,,,,*745762#

Or

Join using audio:

+1 646 558 8656

Presenters

CAPT David Sugerman, MD, MPH, FACEP, USPHS
Chief (Acting), Viral Vaccine Preventable Diseases Branch
Division of Viral Diseases
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention

Adria Mathis, MSPH
Epidemiologist
Division of Viral Diseases
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention

Dan Filardo, MD
Medical Officer
Division of Viral Diseases
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention

ISIRV: Update on H5N1 Panzootic: Infected Mammal Species Increase by Almost 50% in Just Over a Year

A partial sampling of HPAI since Oct 2024

#18,867

In the 4 years HPAI H5N1 began its latest global diaspora, we've witnessed an incredible increase in both its geographic, and host, ranges. The virus has since  conquered both North and South America, has encroached into the Antarctic, and now threatens Australasian. 

Spillovers into mammals - once relatively rare - have become both commonplace and constant; often with devastating neurological impacts.  

Huge populations of marine mammals have been killed, > 1000 dairy herds have been infected, and uncounted thousands of other mammals have died (see also Nature Reviews: The Threat of Avian Influenza H5N1 Looms Over Global Biodiversity).

These milestones have become so common, that events that would have inspired screaming headlines 2 years ago are scarcely noticed today (see Avian Flu's New Normal: When the Extraordinary Becomes Ordinary).

 Today we've a brief update in Influenza & Other Respiratory Viruses that reports - in a climate of reduced surveillance and testing - a nearly 50% increase in the number of mammalian species infected by H5Nx over the past year. 

I've only posted some excerpts. Follow the link to read it in its entirety.  

Update on H5N1 Panzootic: Infected Mammal Species Increase by Almost 50% in Just Over a Year

Pablo Plaza, Sergio A. Lambertucci
First published: 10 September 2025
https://doi.org/10.1111/irv.70159

Funding: This work is supported by the Agencia Nacional de Promoción Científica y Tecnológica (PICT-2018-1623 and PICT-2021-TI-00039) and Universidad Nacional del Comahue (project 04/B260).

The current panzootic caused by the highly pathogenic avian influenza virus A(H5N1) (hereafter, H5N1) is having devastating effects on animal and ecosystem health; the virus has spread globally, causing alarming mortalities in a wide range of domestic and wild animals [1]. By early 2024, at least 50 mammal species had been reported infected by H5N1, with massive mortalities in some cases; viral mutations suggest the virus is adapting to infect mammals [2]. 

This epidemiological situation puts humans at risk due to the potential emergence of a new viral variant capable of triggering a new pandemic. Here, we provide a global update on mammals infected by H5N1 up to July 2025 following the methodology previously used by Plaza et al. [2], which is based on a search of scientific literature and diverse global databases.

1 Mammal Species Infected

We found that between March 2024 and July 2025, 24 new species were recorded as infected, representing almost a 50% increase in the number of species (Figure 1A,B). The current 74 mammalian species known to be infected by this virus include domestic, synanthropic (i.e., wild species that live in human-modified environments and obtain benefits from humans), and wild species (Figure 1A). Humans use some o these species for productive purposes, such as breeding or harvesting for fur and food (Figure 1A), and several may act as mixing vessels (Figure 1A). Even considering the figures are underestimations [1], the Mustelidae family is the most affected (more than 50,000 cases, mostly in captivity for fur production), followed by the families Otariidae (> 24,000 cases, in the wild), Phocidae (> 18,000 cases, in the wild), Canidae (> 11,000 cases, mostly in captivity for fur production), and Bovidae (> 1000 cases, in dairy production) (Figure 1A).
FIGURE 1

Open in figure viewer PowerPoint

(A) Phylogenetic tree of mammalian species reported as infected by H5N1. The color of the species names represents the number of reported cases in the literature and databases. Colored dots indicate whether a species is domestic or synanthropic, used for human production, a potential mixing vessel, or meets all these criteria. (B) Number of species infected from 2020 to March 2024 and from March 2024 up to July 2025. (C) Percentage of species categorized as domestic or synanthropic, used for human production, or considered potential mixing vessels (bubble size represents the percentage magnitude). DS, domestic or synanthropic; HP, used for human production; MV/DS, domestic or synanthropic and potential mixing vessels; MV, potential mixing vessels. See main text for how the data presented in this figure were obtained.

(SNIP)

2 Concluding Remarks

The number of mammalian species infected by this zoonotic pathogen and the number of cases are rapidly increasing (Figure 1A,B). Although increased testing may have influenced this result, the almost 50% rise in species in just over a year is highly concerning. Some species pose a significant risk to humans due to their large populations, close proximity to human settlements, and potential role as mixing vessels.

Surveillance for high-risk species (i.e., mixing vessels with large populations living near humans) should be a global priority. The lack of information about the H5N1 epidemiological situation in some regions (e.g., some areas of the Global South) should be addressed by promoting surveillance programs and providing funds and technology [1].

The most affected mammalian species are those used by humans, particularly in intensive production systems. This makes management of the H5N1 spread challenging because the virus is strongly associated with our unsustainable ways of living and production methods [6]. If this panzootic is not addressed from a holistic, ecological, productive, and interdisciplinary perspective, only palliative action will be possible, with a limited effect in reducing the negative impact of this pathogen. H5N1 is already spread globally—not only in birds but also in mammals; it is time to put all our effort into reducing its impacts on wild and domestic species but also its spread to humans.

        (Continue . . . ) 

Despite its unprecedented global spread, and its increased (mammalian and avian) host range, we continue to treat HPAI H5Nx as if it is the same virus that failed to spark a pandemic in 2006-2008. 

Even if HPAI H5 fails to ever spark a human pandemic, its impact on our shared ecosystem is enormous, and continues to grow.  

While I can't tell you what negative impacts the loss of a Billion+ wild birds, or a quarter of a million marine mammals - or unfathomable numbers of peridomestic mammals -  might have on our society, one thing is certain. 

We are well on our way to finding out. 

Vet. Microbiology: Continuous Evolution of Eurasian Avian-like H1N1 Swine Influenza Viruses with pdm/09-derived Internal Genes Enhances Pathogenicity in Mice

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While H5Nx remains atop most people's pandemic worry list, it is far from the only viral contender making concerning moves in the wild.  Even among the narrow field of influenza A viruses, H5N1 ranks fairly far down the CDC's IRAT list.

In terms of likelihood of emergence, the CDC currently ranks a Chinese EA H1N1 `G4' swine virus at the very top of their list of zoonotic influenza A viruses with pandemic potential, with 3 other North American swine variant viruses scoring higher than H5N1.

Trying to second guess which virus will reach the finish line next is a bit of a mug's game; particularly given our current level of surveillance and data sharing.  Suffice to say: eventually, another pandemic will emerge. 

EA H1N1 `G4' is a reassortant virus, with elements from EA Avian-like viruses, the 2009 pdmH1N1 virus, and TR lineage viruses. Despite sharing the same subtype designation as a currently circulating seasonal strain, it is genetically different enough to pose a genuine public health threat.

The world's attention was first drawn to this emerging swine-origin virus in late 2015, when a group of Chinese scientists (including Hualan Chen) published a paper in PNAS: The Pandemic Potential Of Eurasian Avian-like H1N1 (EAH1N1) Swine Influenza describing its prevalence, genetics, and transmissibility (in ferrets).

In the `Significance' section the authors boiled it down to this:

Here, we found that, after long-term evolution in pigs, the EAH1N1 SIVs have obtained the traits to cause a human influenza pandemic.

Since then we've followed numerous studies on this emerging virus, including a 2020 study in PNAS: Eurasian Avian-like H1N1 Swine Influenza Virus With Pandemic Potential In China, which reported > 10% seroprevalence for the EAH1N1 among swine workers tested, suggesting that EAH1N1 was gaining in its ability to jump species.

This report led to a flurry of `risk assessments' by public health agencies on EA H1N1 `G4', including the CDC, the ECDC and an FAO/OIE/WHO Tripartite Statement.

In early 2021 the CDC ranked a Chinese Swine-variant EA H1N1 `G4' as having the highest pandemic potential of any flu virus on their list, and since then we've seen additional studies that have only exacerbated concerns.

While we've seen no reports of widespread outbreaks in humans in China, surveillance, testing, and reporting of novel flu viruses remains limited and we often only learn - sometimes only years-after-the-fact (see here, here, and here) - when new discoveries are made.

Our last in-depth look at this EA H1Nx G4 strain was just five weeks ago, in  J. Gen. Virology: Evaluation of Pandemic Potential of the Genotype 4 (G4) Swine Influenza Virus using Ex Vivo and In Vitro Cultures of the Human Respiratory Tract.

Today we've got a new study, again out of China, which finds that this EA H1N1 `G4' virus continues to evolve rapidly, has reassorted into new subtypes, and has increased its pathogenicity in mice. 

This is a lengthy, detailed, and at times technical report, and I've only posted the abstract and some excerpt  Those wishing a deeper dive will want to follow the link to read it in its entirety. 

I'll have a brief postscript after the break. 

Continuous evolution of Eurasian avian-like H1N1 swine influenza viruses with pdm/09-derived internal genes enhances pathogenicity in mice
Authors: Riguo Lan , Jizhe Yang, Jixiang Li, Han Li, Xihao Cao, Mengyan Tao, Haoyu Chang, Haili Yu, Qi Tong, Lu Lu, Jinhua Liu , Honglei Sun  shlei668@163.comAuthors Info & Affiliations
https://doi.org/10.1128/jvi.00430-25
 
PDF/EPUB 

ABSTRACT

Swine influenza A virus (swIAV) is an important zoonotic pathogen with the potential to cause human influenza pandemics. Swine are considered “mixing vessels” for generating novel reassortant influenza A viruses. In 2009, a swine-origin reassortant virus (2009 pandemic H1N1, pdm/09 H1N1) spilled over to humans, causing a global influenza pandemic. This virus soon spread back into swine herds and reassorted with the circulating swIAVs. We previously reported that the genotype 4 (G4) reassortant Eurasian avian-like (EA) H1N1 virus, which bore pdm/09- and triple reassortant (TR)-derived internal genes, had been predominant in swine populations of China since 2016, posing a threat to both the swine industry and public health. 

Here, our ongoing surveillance confirmed that G4 EA H1N1 viruses remained the predominant swIAVs in China from 2019 to 2023 and had reassorted with the co-circulating swIAVs, such as the H3N2 virus, to generate novel reassortant EA H1N2 viruses.

Genetic analyses revealed that the pdm/09-derived internal genes of G4 EA H1N1 viruses originated from reassortments between pdm/09 H1N1 and EA H1N1 viruses in 2009–2010 and underwent independent and continuous evolution in the swine host, exhibiting higher evolutionary rates than those of the pdm/09 H1N1 virus circulating in humans.

The accelerated evolution of internal genes enhanced the polymerase activity of G4 EA H1N1 viruses in mammalian cells, resulting in increased viral replication and pathogenicity in mice. This study provides evidence for swine in promoting the genetic evolution of influenza A virus and highlights the need for increased attention to novel reassortant viruses in swine.

IMPORTANCE

The emergence of pdm/09 H1N1 virus highlights the role of swine influenza A viruses (swIAVs) in generating novel influenza viruses with pandemic potential. Since 2009, the pdm/09 H1N1 virus has been frequently transmitted to swine and reassorted with the circulating swIAVs, generating many new reassortant viruses bearing pdm/09-derived genes globally. The G4 EA H1N1 viruses, which bore pdm/09-derived internal genes and acquired increased human infectivity, remained the predominant swIAVs in China from 2019 to 2023 and reassorted with the co-circulating swIAVs to generate novel subtype viruses. The internal genes of G4 EA H1N1 viruses originated from the human pdm/09 H1N1 viruses during 2009–2010 and exhibited higher evolutionary rates and greater genetic diversity than those in the human host. This has contributed to increased viral adaptation and pathogenicity in mammals. Therefore, sustained surveillance and immunization efforts are essential to control emerging reassortant swIAVs and protect public health.

       (SNIP)

In summary, our findings show that the independent and accelerated evolution of pdm/09-derived internal genes within the swine host has enhanced both the infectivity and pathogenicity of the G4 EA H1N1 virus to mice. These G4 EA H1N1 viruses contribute to the emergence of novel reassortant viruses, thereby increasing the risk to human public health. Consequently, implementing continuous surveillance and proactive immunization strategies is essential to control these viruses. These steps are crucial for managing novel reassortant swIAVs and preventing future human pandemics.

       (Continue . . .)

 
In last month's report we learned that EA H1N1 G4 replicates competently in human bronchial and lung tissue explants, which would allow for both upper and lower respiratory infections.

It also binds preferentially to a2,6-linked sialic acid receptors cells, which are abundant in the human upper airway. Past studies suggest that population immunity to these EA H1Nx viruses would be low.

While there are reasons to believe EA H1N1 might not produce as severe of a pandemic (in terms of mortality) as an avian H5 or H7 pandemic virus, even a 1%-2% CFR - when combined with a high attack rate - would present a grave threat. 

But as far as I can see, the world isn't even remotely ready for that level of a pandemic, much less something on the level of SARS-CoV, MERS-CoV, or H5Nx.

Which is why I continue to promote personal preparedness (see A Personal Pre-Pandemic Plan).