H5N1 in California: The Return of the Fly

  

#18,799

Late yesterday Raj Rajnarayanan @RajlabN - Associate Dean of Research and Associate Professor, NYITCOM at Arkansas State University - uploaded to X/Twitter a quick analysis of H5N1 sequences sampled from a HouseFly uploaded to @GISAID from California (2.3.4.4b B3.13 Collected Oct 2024). 

While this caused a bit of a stir online, it is not an unexpected finding. 

 

Very early on in this blog (2007) - in Cats and Dogs and Flies, Oh My! - we looked at a 2006 study (see Detection and isolation of highly pathogenic H5N1 avian influenza A viruses from blow flies collected in the vicinity of an infected poultry farm in Kyoto, Japan, 2004 by Kyoko Sawabe et al.) that found that at least 2 types of flies could carry the H5N1 virus.

While flies weren't shown to be infected with the virus, they could ingest (and subsequently regurgitate or defecate) infected material, or potentially spread it mechanically by their feet or body, thereby spreading the disease.

Four years later Dr. Sawabe and his team would publish (Blow Flies Were One of the Possible Candidates for Transmission of Highly Pathogenic H5N1 Avian Influenza Virus during the 2004 Outbreaks in Japan) where they conclude:

We have suggested here that blow flies are likely candidates for mechanical transmission of HPAI because of their ecological and physiological characteristics as reviewed here. In fact, blow flies have already been recognized as important vectors for mechanical transmission of several serious infectious diseases, that is, poxvirus [28], rabbit hemorrhagic disease [29], and paratuberculosis [30]. Recently, it has been reported that the H5N1 viral gene was detected in house flies [31] and engorged mosquitoes [32].

While we're not talking about classically 'infected' flies, it seems likely that contaminated flies may be one of many contributors to the spread of the HPAI virus.  

Much in the same way that contaminated personnel or vehicles moving between farms can spread the virus (see the APHIS/USDA epidemiological investigation into the spread of H5N1 in Michigan).

Eighteen months ago, we looked at a preprint (later published in Sci Repts: Blowflies As Potential Vectors Of Avian Influenza) that tested blowflies for HPAI at the national wildlife reserve in Izumi City, Kagoshima Prefecture, which is the overwintering home for thousands of endangered Hooded Cranes.

The authors wrote:

In December 2022, 648 Calliphora nigribarbis were collected. Influenza virus RT-PCR testing identified 14 virus-positive samples (2.2% prevalence), with the highest occurrence observed near the crane colony (14.9%). Subtyping revealed the presence of H5N1 and HxN1 in some samples. Subsequent collections in December 2023 identified one HPAI virus-positive specimen from 608 collected flies in total, underscoring the potential involvement of blowflies in HPAI transmission.

Our observations suggest C. nigribarbis may acquire the HPAI virus from deceased wild birds directly or from fecal materials from infected birds, highlighting the need to add blowflies as a target of HPAI vector control.

As one might expect, this study got a lot of attention in the Japanese press, with Dr. Ryusuke Fujita quoted as saying,

`Until now, countermeasures have been taken based on the assumption that small animals and people will bring the virus. There was no improvement, and when we suspected it was a fly, a virus was detected.

We will conduct a more detailed investigation, take measures to prevent fly intrusion, and verify their effectiveness."

HPAI H5 has become pervasive in wild birds, and has spilled over into numerous terrestrial and marine mammals, making its containment or control far more difficult than it was even a few short years ago.  

Evidence suggests the HPAI virus spreads through multiple, highly complex,  processes.  Yet we continue to takes something less than a holistic approach, still hoping they will contain the threat. 

The USDA's Enhanced Biosecurity guidance (updated 6/25) focuses primarily on `big ticket' items like limiting visitors, disinfecting tools and shoes, and avoiding the mixing of animals species. 

While all are reasonable recommendations, they haven't prevented the spread of HPAI H5 to nearly 1,100 dairy herds, and more than 1,700 poultry farms in the United States since late 2021. 

In addition to flies as potential vectors, we've looked at a number of other `less obvious' ways the virus may be spreading. 

• There is growing evidence that HPAI may be spread via `contaminated dust particles' - carried by the wind - from one farm to the next (see Preprint: Genetic & Meteorological Data Supporting Windborne Transmission of HPAI H5N1).

• The role of peridomestic mammals - particularly in and around farms - in the spread of HPAI is only partially understood, and remains under-researched (see Emer. Microbe & Inf.: HPAI Virus H5N1 clade 2.3.4.4b in Wild Rats in Egypt during 2023).

• While contaminated milking machines have been blamed for the cow-to-cow spread of HPAI, a recent preprint (Dairy Cows Infected with Influenza A(H5N1) Reveals Low Infectious Dose and Transmission Barriers) was unable to duplicate transmission in a controlled lab setting, leading researchers to warn `. . . Other agent, host, and environmental cofactors that might contribute to transmission cannot be ruled out and must be explored . . . ).

Unless and until we get a better handle on how HPAI is spreading in the wild - and among and between farms - our ability to slow or contain these outbreaks will remain limited. 

But research remains sporadic, with many farmers - fearing loss of income or the stigma of infection - opting for a `Don't test, don't tell' strategy. The USDA's powers and jurisdiction - like the CDC's - are often limited in these cases.

How much house flies, windborne `poultry dust', or peridomestic rodents contribute to the spread of HPAI is unknown. But these are risk factors that could be better controlled than they currently are, and should be worth exploring.

Co-circulation of distinct HPAIV subtypes in a Mass Mortality Event in Wild seabirds and Co-location with Dead Seals

 

Credit UK APHA

#18,798

Influenza viruses are constantly evolving, and while most of these new iterations are evolutionary failures, occasionally a more biologically `fit' variant emerges, that is able to compete with older strains. 

Over the past two decades we've seen several major shifts in dominant H5 subtypes (H5N1 → H5N8 → H5N6 → H5N1), and a long procession of new clades and subclades. 

While H5N1 clade 2.3.4.4b is currently the dominant strain, 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).  

Complicating matters, when these (and other influenza A viruses) infect a common host, they sometimes create a new hybrid (subtype, genotype, etc.) virus; aka a reassortment.

While many of these reassortants are short-lived, one persistent offshoot we've been watching with considerable interest is HPAI H5N5, a subtype that was first reported in 2011's  EID Journal: Novel H5N5 Avian Influenza Detected In China.

H5N5 reappeared during Europe's first major avian (H5N8) epizootic in 2017 (see Netherlands Finds 2 Dead Geese With HPAI H5N5). Although a relatively minor player, this newly emerged H5N5 virus was described as `highly aggressive' by Germany authorities.

Reports of H5N5 dwindled in 2018, but the subtype remerged in Russia in the fall of 2020, and began slowly spreading across Northern Europe (see Denmark Reports HPAI H5N5 In Peregrine Falcon).

A little over 2 years ago (May 2023), H5N5 appeared in Eastern Canada on Prince Edward Island (see CIDRAP Report Canada reports first H5N5 avian flu in a mammal). 

We checked back again in the spring of 2024 with HPAI H5N5: A Variation On A Theme, and with WAHIS: More Reports of HPAI H5N5 in Canada.

Last July, 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.

 The authors wrote:

Thus, while A(H5N5) viruses are comparably uncommon, their high virulence and mortality potential demand global surveillance and further studies to untangle the molecular markers influencing virulence, transmission, adaptability, and host susceptibility.

Last November, in UK: HPAI H5N5 Rising, we saw a sudden shift in H5N5 activity in wild birds in the UK, with the APHA reporting:

Since our previous outbreak assessment on 7 October 2024, there have been no new reports of high pathogenicity avian influenza (HPAI) H5 clade 2.3.3.4b in domestic poultry in Great Britain (England, Scotland and Wales). There have, however, been 15 more HPAI H5 clade 2.3.3.4b events involving 26 “found-dead” wild birds in Great Britain. Of these, 25 were HPAI H5N5 with 1 case of HPAI H5N1.

The plot thickened again last February when the UK Confirms HPAI H5N5 In 2 Grey Seals in Norfolk.  In March the APHA confirmed even More Detections (n=13) of HPAI H5N5 In Seals, again in Norfolk.   

All of which brings us to a preprint by researchers at the UK's APHA (Animal Plant Health Agency) on the co-circulation of HPAI H5N1 and H5N5 in wild seabirds and seals in the UK. 

While H5N5 continues to be overshadowed by H5N1, it has shown remarkable resilience, and continues to gain ground.

 It also carries several worrisome mammalian adaptations (PB2-E627K and a 22-amino acid stalk deletion in NA) that may make it more of a threat to humans (and other mammals). 

The concern is the close co-circulation of these two distinct subtypes may provide opportunities for new, even more worrisome, reassortants to emerge. I've only reproduced the abstract and a few excerpts below, so follow the link to read the preprint in its entirety. 

Co-circulation of distinct high pathogenicity avian influenza virus (HPAIV) subtypes in a mass mortality event in wild seabirds and co-location with dead seals
 
Marco Falchieri, Eleanor Bentley, Holly A. Coombes, Benjamin C. Mollett, Jacob Terrey, Samantha Holland, Edward Stubbings, Natalie Mcginn, Jayne Cooper, Samira Ahmad, Jonathan Lewis, Ben Clifton, Nick Collinson, James Aegerter, Divya Venkatesh, Debbie J. F. Russell, Joe James, Scott M. Reid, Ashley C. Banyard

doi: https://doi.org/10.1101/2025.07.11.664278

        PDF 

Abstract

H5Nx clade 2.3.4.4b high pathogenicity avian influenza viruses (HPAIV) have been detected repeatedly in Great Britain (GB) since autumn 2020, with H5N1 dominating detections but with low level detection of H5N5 during 2025. Globally, these viruses have caused mass mortalities in captive and wild avian and mammalian populations, including terrestrial and marine mammals. H5N1 has been the dominant subtype, and whilst incursions have overlapped temporally, occurrences have often been spatially distinct.

Here, we report the detection of a mortality event in wild birds on the Norfolk coastline in the east of England, where H5N1 HPAIV was detected in five Great Black-backed Gulls (Larus marinus) and a Northern Fulmar (Fulmarus glacialis).

Interestingly, at the same site, and as part of the same mortality event, a total of 17 Great Black-backed Gulls, one Herring Gull (Larus argentatus), one Atlantic Puffin (Fratercula arctica) and one Northern Fulmar tested positive for H5N5 HPAIV. Additionally, H5N5 was also detected in 17 co-located Grey Seal carcases (Halichoerus grypus).

The H5N1 HPAIV from an infected bird belonged to genotype DI.2, closely related to contemporaneous detections in GB wild birds and poultry. In contrast, all H5N5 HPAIVs from birds and seals were genotype I with a 22-amino acid stalk deletion in NA and the 627K polymorphism in PB2. This represents the first recorded instance in GB of two subtypes being detected within the same avian population at the same location. It is also the first mass detection of HPAIV H5N5 in mammals within GB. Potential infection mechanisms are discussed.

       (SNIP) 

The co-circulation of distinct subtypes and genotypes within species occupying the same temporal, spatial and ecological landscapes raise important questions regarding the potential for viral reassortment and the role of gulls in the emergence of novel genotypes.

Numerous H5N1 genotypes have been described in each previous season dominated by H5N1 viruses, although a few genotypes were detected more frequently [35, 54]. Interestingly, since the beginning of the 2024/25 AIV season in GB, genotype diversity has been limited with DI.2 dominating positive avian detections [62]. 

Alongside DI.2, only the BB genotype, a previously dominant genotype, has been detected with some regularity, predominantly in the South-West of England in gull species that links with occasional detections in continental Europe [54]. Further, there have been two detections of the DI.1 genotype in wild birds in 2024, both have been of Norfolk, and it has not been detected since. Interestingly the contemporary H5N5 detections appear to be entirely represented by a single genotype (genotype I), with no evidence of reassortment. 

Further, since the emergence of the H5N1 BB genotype in 2022, this has also exhibited predominately in gull species with limited reassortment. How and why different HPAIV genotypes are generated, and either dominate or disappear, remains a significant knowledge gap although several studies have demonstrated differential shedding and clinical impact in poultry species and it is likely that similar occurs in wild birds. 

In conclusion, the detection of two subtypes, H5N1 and H5N5 in avian species linked to a mammalian mortality event that appears restricted to infection with a single H5N5 subtype is of high interest. Conditions for sampling carcasses were sub-optimal and the environmental conditions within which these detections were made precluded further swabbing and assessment. 

Regardless, it is important to define and describe such detections as they clearly demonstrate that different viral subtypes can be present within a mortality event without reassortment being detected. Understanding the intra and inter-species infection and transmission dynamics is of high interest. 

        (Continue . . . )

 

Globally there are scores of HPAI H5 variants (clades, subclades, subtypes, and genotypes), many circulating in multiple different hosts (e.g. marine mammals, livestock, peridomestic animals, wild birds and poultry) - each on their own evolutionary path. 

Between antigenic drift and antigenic shift (reassortment), the HPAI H5Nx viruses that return next fall or next year could easily be more - or less - of threat than what we've seen thus far. Evolution is a double-edged sword, and what it adds it can also take away.

 

But evolution never stops. 

Which is why - even though we find ourselves enjoying a relatively quiet avian flu summer - we can't afford to stop preparing either.  

JGV Review Article: Coronaviruses in Wild rodent and Eulipotyphlan Small Mammals

 
Map showing origins & paucity of studies available for this Review

#18,796

For most of the past 120+ years, influenza A has been considered the biggest pandemic threat. It is easily spread between humans (and other mammals), it is highly mutable, it can produce severe (even fatal) illness, and it has sparked pandemics in 1918, 1957, 1968, and 2009. 

In 2002-2003, an unprecedented epidemic of SARS briefly spread out of China (see SARS and Remembrance), demonstrating for the first time that a novel coronavirus might have pandemic potential. 

Previously only 4 mild coronaviruses (Alpha coronaviruses 229E and NL63, and Beta coronaviruses OC43 & HKU1) - only thought capable of producing `common cold' symptoms - had been identified in humans. 

While some thought SARS was a warning, others dismissed it as a fluke.  

That is, until a decade later when another (more) severe coronavirus - MERS-CoV - appeared on the Arabian Peninsula, infecting thousands and killing hundreds over the past 13 years.  

Relatively large (and usually nosocomial) outbreaks have been recorded (see Two MERS-CoV Hospital Super Spreading Studies) - but widespread community transmission has yet to be reported.

Although camels have been identified as the primary vector of MERS-CoV to humans, as with SARS-CoV, a bat reservoir host is strongly suspected.  

If MERS-CoV raised concerns over the impact of coronaviruses, then SARS-CoV-2 erased all doubts. COVID produced the worst pandemic in more than 100 years; official death tolls cite 7 million COVID deaths, but estimates put it  3 to 4 times higher.

Over the past dozen years most of the research on the origins of SARS-like viruses has focused on bats.

EID Journal: A New Bat-HKU2–like Coronavirus in Swine, China, 2017

Emerg. Microbes & Infect.: Novel Coronaviruses In Least Horseshoe Bats In Southwestern China

SARS-like WIV1-CoV poised for human emergence

But in recent years we've also seen growing interest on the role played by rodents (mice & rats) and Eulipotyphla (hedgehogs, moles, shrews, etc.) in the carriage, evolution, and spread of zoonotic viruses; including novel coronaviruses. 

These ubiquitous mammals are capable of hosting and spreading a wide range of pathogens, including H5N1, SARS-CoV2, and henipaviruses (see Nature: Decoding the RNA Viromes in Shrew Lungs Along the Eastern Coast of China).

 

Rats and mice are also capable of carrying coronaviruses, including SARS-CoV-2 (see mBio: SARS-CoV-2 Exposure in Norway Rats (Rattus norvegicus) from New York City).  In Preprint: SARS-CoV-2 Infection in Domestic Rats After Transmission From Their Infected Owner, we saw further evidence of the susceptibility of rodents to COVID.

Just last March, in Novel Rodent Coronavirus-like Virus Detected Among Beef Cattle with Respiratory Disease in Mexico, we looked at the discovery of a novel coronavirus that most closely resembled a rodent-coronavirus first isolated in China in 2021. 

All of which brings us to an excellent literature review article - published last week - which looks at research on these lesser studied hosts. Due to its length, I've only posted the link and some excerpts. 

I'll have a postscript when you return. 

Coronaviruses in wild rodent and eulipotyphlan small mammals: a review of diversity, ecological implications and surveillance considerations

Simon P. Jeeves1​, Jonathon D. Kotwa2, David L. Pearl3​, Bradley S. Pickering4​,5​, Jeff Bowman6​,7​, Samira Mubareka2​,8​ and Claire M. Jardine1​,9​
 
Published: 11 July 2025 https://doi.org/10.1099/jgv.0.002130
 
ABSTRACT

Coronaviruses are abundant and diverse RNA viruses with broad vertebrate host ranges. These viruses include agents of human seasonal respiratory illness, such as human coronaviruses OC43 and HKU1; important pathogens of livestock and domestic animals such as swine acute diarrhoea syndrome coronavirus and feline coronavirus; and human pathogens of epidemic potential such as SARS-CoV, MERS-CoV and SARS-CoV-2.

Most coronavirus surveillance has been conducted in bat species. However, small terrestrial mammals such as rodents and eulipotyphlans are important hosts of coronaviruses as well. Although fewer studies of rodent and eulipotyphlan coronaviruses exist compared to those of bats, notable diversity of coronaviruses has been reported in the former. 

No literature synthesis for this area of research has been completed despite (a) growing evidence for a small mammal origin of certain human coronaviruses and (b) global abundance of small mammal species. In this review, we present an overview of the current state of coronavirus research in wild terrestrial small mammals. We conducted a literature search for studies that investigated coronaviruses infecting rodent and eulipotyphlan hosts, which returned 63 studies published up to and including 2024. 

We describe trends in coronavirus diversity and surveillance for these studies. To further the examination of the interrelatedness of these viruses, we conducted a phylogenetic analysis of coronavirus whole genomes recovered from rodent and eulipotyphlan hosts. We discuss important facets of terrestrial small mammal coronaviruses, including evolutionary aspects and zoonotic spillover risk. Lastly, we present important recommendations and considerations for further surveillance and viral characterization efforts in this field.

        (SNIP)

Conclusion

Research, surveillance and management of animal CoVs requires a One Health approach that considers the health of humans, wildlife, domestic animals and the ecosystems where they coexist. While research into the diversity of these viruses in bats is abundant, similar investigations in rodents and eulipotyphlans are comparatively limited.

This is particularly so in the Americas, Australia and Oceania where, despite diverse populations of wild terrestrial small mammal species, only 13.3% of the identified studies in this review were conducted (Fig. 1 and Table 1). However, in the last decade, the number of studies of CoV diversity in rodent and eulipotyphlan small mammals has been increasing.

While thorough work has been done to characterize the viruses identified, major gaps remain in understanding the ecology of these viruses in their hosts. Elucidating environmental and demographic factors involved in the reservoir ecology and sylvatic transmission of potentially zoonotic CoVs can allow steps to be taken for avoiding spillover to humans or controlling spread among animal populations [128]. Such steps include identifying target host species, environmental interfaces and sample types for further CoV surveillance.

It is clear that CoVs present a zoonotic threat. If the ecology of these viruses remains poorly understood, then novel spillover events – whether to humans or other species – will continue to be a threat.

        (Continue . . . )

While much of the world has paid relatively little notice to the zoonotic threat posed by these small peridomestic mammals, Chinese scientists continue to show great interest; of the 63 studies contained in this review, 26 (41.5%) originated in China. 

While more research is needed, a few related studies we've reviewed from the past year include:

Nature: Virome Characterization of Field-Collected Rodents in Suburban City

Viruses Review - The Hidden Threat: Rodent Borne Diseases

Experimental Infection of Rats with Influenza A Viruses: Implications for Murine Rodents in Influenza A Virus Ecology

EID Journal: Henipavirus in Northern Short-Tailed Shrew, Alabama, USA

Pathogens: Susceptibility of Synanthropic Rodents to H5N1 Subtype HPAI Viruses

Emer. Microbe & Inf.: HPAI Virus H5N1 clade 2.3.4.4b in Wild Rats in Egypt during 2023

SSI: Large Danish Study Shows No Link Between Aluminum in Vaccines & Autism or Other Health Conditions

 

Credit ACIP/CDC

#18,795

Today the journal Annals of Internal Medicine has published a major study by researchers at Denmark's Statens Serum Institut (SSI) and the University of Copenhagen, which followed more than 1 million children (born between 1997 and 2018) who received childhood vaccines.

Significantly, they found no link between vaccine receipt and autism (and > 4 dozen other health conditions).

Due to their relatively small population (5.9 million) and a well-monitored universal healthcare system, Denmark's ability to conduct population based health studies is viewed as among the best in the world. 

The study may be accessed at:

Andersson NW, Bech Svalgaard I, Hoffmann SS, et al. Aluminum-adsorbed vaccines and chronic diseases in childhood. A nationwide cohort study. Ann Intern Med. 15 July 2025. doi:10.7326/ANNALS-25-00997

Those looking for a more easily digested synopsis will find it in the following (translated) media release from the SSI.  I'll have a postscript after the break.

Large Danish study: No link between vaccines and autism or 49 other health conditions

A new Danish study shows no link between aluminum in childhood vaccines and 50 health conditions such as autism, asthma and autoimmune disorders. The study thus confirms the safety of the Danish childhood vaccination program.

Last edited on July 15, 2025



A new, comprehensive Danish registry study, the largest of its kind to date, supports the safety of the Danish childhood vaccination program. The study, which includes data from over 1 million children, thus finds no increased incidence of, for example, autism, asthma or autoimmune disorders in vaccinated children.

"Our results are reassuring. By analyzing data from hundreds of thousands of Danish children, we have not found anything that indicates that the very small amount of aluminum used in the childhood vaccination program increases the risk of 50 different health conditions in childhood," says doctor Niklas Andersson from the Staten Serum Institut (SSI), who is the first author of the study.

The very small amounts of aluminum, which are included in certain vaccines as an adjuvant to enhance the effect, have been used since the 1930s.

The researchers from SSI have followed children born between 1997 and 2018 through the Danish health registries and analyzed the connection between vaccines containing aluminum and a total of 50 health conditions - including allergies, autoimmune disorders, neurological diseases and developmental disorders.

"It is the first study of this size and with such extensive analyses, and it confirms the high safety of the vaccines we have used for decades in Denmark," says Niklas Andersson.

The results are being published at a time when there is intense international debate about vaccine safety. Therefore, the Danish study comes at a particularly relevant time.

"In a time characterized by widespread misinformation about vaccines, it is crucial to be able to lean on solid scientific evidence. Large, population-based registry studies like this, which follow hundreds of thousands of children over many years, are part of the bulwark against the politicization of health knowledge, which can damage trust in vaccines. It is absolutely crucial that we clearly separate real science from politically motivated campaigns - otherwise we risk that it is Danish children who pay the price," says Department Head Anders Hviid from SSI, who led the large study.
Reference

Andersson NW, Bech Svalgaard I, Hoffmann SS, et al. Aluminum-adsorbed vaccines and chronic diseases in childhood. A nationwide cohort study. Ann Intern Med. 15 July 2025. doi:10.7326/ANNALS-25-00997

Facts about the study

• Researchers from the Statens Serum Institut (SSI) have analyzed data from more than 1 million Danish children born between 1997 and 2018 through Denmark's unique health registries to investigate whether there were long-term health effects of aluminum-containing vaccines.
• The study examined 50 different disorders and found no statistical correlation between the aluminum content in vaccines and an increased risk of developing autism, autoimmune disorders, asthma, or allergic diseases such as hay fever and food allergies.
• The study has just been published in the prestigious medical journal Annals of Internal Medicine.

Source: SSI

Fifteen years ago, in a blog called `The Monsters Are Due On Vaccine Street' I recalled a famous Twilight Zone episode, and noted that some of the same tactics were being used to undermine the public's faith in vaccines. 

`All it takes is for someone to instill a bit of doubt .  . .   a modicum of suspicion . . .  backed up by random, but seemingly connected events . . . and our insecurities, fears, and prejudices do the rest.'

Today, with overwhelming power of social media, what was once essentially a fringe movement has now become mainstream.  Propelled by `influencers' and glossy AI generated `clickbait' videos, quackery and misinformation abounds. 

• Childhood vaccine uptake is down, while measles and pertussis are rising (see Washington DOH Reports 25-fold Increase In Pertussis Cases in 2024 over 2023).  

• Flu vaccinations peaked in the last decade and have since declined, and only a small percentage of the population bothers with COVID shots anymore.  

Modern vaccines - including the COVID mRNA vaccines - have an enviable safety record. That said, there is no such thing as a 100% safe drug or medication for 100% of the population, and some adverse effects can occur. 

Even over-the-counter remedies, like NSAIDs or acetaminophen, can sometimes produce adverse - even fatal - reactions (see BMJ Research: NSAIDs & The Risk Of Heart Failure).

The decision to take any vaccine or medication should always be based on a risk-reward calculation.  Most of the time, those benefits far outweigh the risks.

But to analyze it properly, one needs to be able to distinguish pertinent facts from unsupported propaganda. 

A skillset that appears to be waning rapidly in today's society.

WHO: Influenza at the Human-Animal Interface Summary and Assessment, 1 July 2025

 

#18,794

Overnight the WHO published their June 2025 update on novel influenza (covers May 28th-July 1st), which adds 10 human H5N1 cases, 3 human H9N2 infections, and a 6th H10N3 case in China. 

Although the H9 and H10 cases were previously reported (see WHO WPRO Reports 6th H10N3 Case & 3 Additional H9N2 Cases In China), as were 8 H5N1 cases from Cambodia last month, there are 2 previously unannounced H5N1 cases in today's report (Bangladesh & India). 

Given the cutoff date of July 1st, Cambodia's latest case was not included. First, the summary, then we'll dig into some specifics on last month's cases.

Influenza at the human-animal interface

Summary and risk assessment, from 28 May to 1 July 20251

• New human cases : From 28 May to 1 July 2025, based on reporting date, the detection of influenza A(H5N1) in nine humans, influenza A(H9N2) in three humans and influenza A(H10N3) in one human were reported officially. Additionally, one human case of infection with an influenza A(H5N1) virus was detected.

• Circulation of influenza viruses with zoonotic potential in animals: High pathogenicity avian influenza (HPAI) events in poultry and non-poultry continue to be reported to the World Organisation for Animal Health (WOAH).3 The Food and Agriculture Organization of the United Nations (FAO) also provides a global update on avian influenza viruses with pandemic potential.4

• Risk assessment: Sustained human to human transmission has not been reported from these events. Based on information available at the time of the risk assessment, the overall public health risk from currently known influenza viruses circulating at the human-animal interface has not changed remains low. The occurrence of sustained human-to-human transmission of these viruses is currently considered unlikely. Although human infections with viruses of animal origin are infrequent, they are not unexpected at the human-animal interface.

• IHR compliance: All human infections caused by a new influenza subtype are required to be reported under the International Health Regulations (IHR, 2005).6 This includes any influenza A virus that has demonstrated the capacity to infect a human and its haemagglutinin (HA) gene (or protein) is not a mutated form of those, i.e. A(H1) or A(H3), circulating widely in the human population. Information from these notifications is critical to inform risk assessments for influenza at the human-animal interface.

A little over 5 weeks ago, in the May 2025 WHO Summary, we learned of 2 previously undisclosed H5 cases (clade 2.3.2.1a ) from Bangladesh; both collected from young children in Khulna Division last spring.  

Today's update provides a third case, this time from Chittagong division (> 250 Km to the east). 

A(H5N1), Bangladesh

On 31 May 2025, Bangladesh notified WHO of one confirmed human case of avian influenza A(H5) in a child in Chittagong division detected through hospital-based surveillance. The patient was admitted to hospital on 21 May with diarrhea, fever and mild respiratory symptoms and a respiratory sample was collected on admission.

On 28 May, the IEDCR confirmed infection with avian influenza A(H5) through RT-PCR. The N-type was later confirmed as N1. The patient has recovered, and exposure to backyard poultry was reported prior to symptom onset. No further cases were detected among the contacts of the case.

This is the 11th human infection with influenza A(H5N1) notified to WHO from Bangladesh since the first case was reported in the Dhaka division in 2008 and the third confirmed case in 2025.

The second new case (from India) remains somewhat of a mystery.  Not only is the report quite brief, the location provided (Khulna State) is a bit confusing, as Khulna is located in Bangladesh, not India. 

A(H5N1), India

A human infection with an H5 clade 2.3.2.1a A(H5N1) virus was detected in a sample collected from a man in Khulna state in May 2025, who subsequently died. Genetic sequence data are available in GISAID (EPI_ISL_19893416; submission date 4 June 2025; ICMR-National Institute of Virology; Influenza).

Today's report provides a more extensive review of the 8 cases reported by Cambodia last month:

Brief updates on the H9 and H10 cases are also included:

A(H9N2), China

Since the last risk assessment of 27 May 2025, three human cases of infection with A(H9N2) influenza viruses were notified to WHO from China on 9 June 2025. The cases were detected in Henan, Hunan and Sichuan provinces. Two infections were detected in adults who were also hospitalized. The cases had symptom onset in May 2025 and have recovered. All cases had a known history of exposure to poultry prior to the onset of symptoms. No further cases were detected among contacts of these cases and there was no epidemiological link between the cases. 

 

A(H10N3), China

On 9 June 2025, China notified the WHO of one confirmed case of human infection with avian influenza A(H10N3) virus in an adult from Shaanxi Province, with a history of asthma. Symptom onset occurred on 21 April, and the patient was admitted to hospital with pneumonia on 25 April. At the time of reporting, that patient was under treatment and improving. 

According to the epidemiological investigation, a history of exposure to backyard poultry in Inner Mongolia was reported. The patient is a farmer and raises chickens and sheep. Environmental samples did not test positive for influenza A(H10) viruses. All close contacts tested negative for influenza A and remained asymptomatic during the monitoring period.

Since 2021, China has notified WHO of a total of six confirmed human cases of avian influenza A(H10N3) virus infection.

In addition to these case updates, the WHO once again implores member nations to abide by the 2005 IHR regulations which require prompt notification of the WHO of all human infections caused by novel flu subtypes.

According to a report 2 years ago (see Lancet Preprint: National Surveillance for Novel Diseases - A Systematic Analysis of 195 Countries) many member nations still lack the capability to fully investigate cases, while others simply choose not to for economic, societal, or political reasons.

For a multitude of reasons, the cases that do get reported are almost certainly just the tip of a much larger iceberg.  And as this report illustrates, there is more than just H5N1 percolating in the wild. 

Preprint: Neuraminidase Imprinting and the Age-related Risk of Zoonotic Influenza

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History has shown that influenza pandemics can vary widely, both in severity and in demographic impact. The 1918 H1N1 pandemic was not only high-severity, it was reportedly far deadlier to healthy young adults than to the elderly (see epi curve above). 

In 2010, (see Study: Years Of Life Lost Due To 2009 Pandemic), researchers estimated the median age of death due to seasonal influenza-related illness in the United States to be 76. 

But in the 1957 H2N2 pandemic, and again in 1968's H3N2 pandemic, we saw a pronounced age shift to a younger cohort (see Pandemic versus epidemic influenza mortality: a pattern of changing age distribution).

`Half of influenza-related deaths during the 1968-1969 influenza A (H3N2) pandemic and large proportions of influenza-related deaths during the 1957-1958 influenza A (H2N2) and the 1918-1919 influenza A (H1N1) pandemics occurred among persons <65 years old.'

While the 2009 H1N1 pandemic was milder, we saw an even greater age shift. The CDC’s estimate of average and median age of death due to the 2009 Pandemic virus reads:

Based on two CDC investigations of confirmed 2009 H1N1-related deaths that occurred during the spring and fall of 2009, the average age of people in the U.S. who died from 2009 H1N1 from April to July of 2009 was 40. The median age of death for this time period was 43. From September to October of 2009, the average age of people in the U.S. who died from 2009 H1N1 was 41, and the median age was 45.

Bucking these trends, the 5-year epidemic of H7N9 in China had its greatest impact on older adults and the elderly (see "Avian influenza A (H7N9) virus infections in humans across five epidemics in mainland China, 2013–2017). The authors wrote: 

A linear increase in fatality risk was observed from the younger age groups to older age groups (Figure 4B). Case-patients aged over 60 years consistently had higher risks for death, death/mechanical ventilation, death/mechanical ventilation/ICU admission than case-patients aged below 60 years.

Yet H5N1, which is currently high on our watch list, has consistently skewed towards a younger demographic. Eighteen years ago, in A Predilection For The Young, I wrote about the disturbing skewing of H5N1 cases (and deaths) among younger individuals (see WHO Chart below).

More recently (see here, and here) we've looked at the skewing of fatal H5N1 cases in Cambodia towards a younger cohort.

Over the past decade it as become increasingly apparent that the first influenza virus you are exposed to shapes your immune response to other subtypes later in life (see Nature: Declan Butler On How Your First Bout Of Flu Leaves A Lasting Impression).

While the subtype (H1, H2, H3, etc.) is often assumed to have the biggest impact, the HA Group type (see chart below) can also drive future immune responses (see Science: Protection Against Novel Flu Subtypes Via Childhood HA Imprinting).

Obviously, knowing what cohorts or risk groups would be most vulnerable in a future influenza pandemic would greatly aid in preparedness, and in the allocation of vaccines and antivirals. 

But, as today's preprint by Danuta M. Skowronski et al. reports that immune imprinting may depend on more than just the first HA exposure, as the first NA (neuraminidase) may play a significant role as well.

This is a fascinating report, which adds both H5N6 and H9N2 to the equation. Despite sharing a near-identical HA with H5N1, H5N6 consistently skews towards an older demographic.

H9N2, on the other hand, skews to an even younger cohort than H5N1.

This paper posits that the lower attack rate and CFR from H5N1 over the past 15 years may be due to the `original pediatric priming' of children from the NA of the 2009 H1N1 pandemic, and a `massive boost opportunity' for older cohorts who were first exposed to H1N1 (born prior to 1957).

The authors also suggest that while this anti-NA immunity may help moderate the severity of both H5N1 and H9N2, it may also represent a double-edge sword. They write:

Homosubtypic anti-NA in particular may have attenuating effects on H5N1 and H9N2 zoonotic risk, notably severity, with implications for targeted messaging and mitigation measures.

Alternatively, while beneficial to those directly exposed, anti-NA may also paradoxically contribute to unrecognized infections, potentially facilitating surreptitious shedding, spreading and viral adaptation, with implications for case detection, containment and enhanced surveillance.

There is a lot to unpack here, and you'll want to download and read the full report.  I'll have a bit more after the break.

Neuraminidase imprinting and the age-related risk of zoonotic influenza

Danuta M. Skowronski, Samantha E. Kaweski, Lea Separovic, Suzana Sabaiduc, Gabriel Canizares, Ayisha Khalid, Charlene Ranadheera, Nathalie Bastien, Gaston De Serres

doi: https://doi.org/10.1101/2025.07.03.25330844

Highly pathogenic avian influenza of the H5N1 subtype has shown recent unprecedented expansion in its geographic and host range, increasing the pandemic threat. The younger age of H5N1 versus H7N9 avian influenza in humans has previously been attributed to imprinted pre-immunity to hemagglutinin stalk (HA2) epitopes shared with group 1 (H1N1, H2N2) versus group 2 (H3N2) influenza A subtypes predominating in the human population before versus after 1968, respectively.

Here we review the complex immuno-epidemiological interactions underpinning influenza risk assessment and extend the imprinting hypothesis to include a potential role for cross-protective neuraminidase (NA) imprinting. We compare H5N1 distributions and case fatality ratios by age and birth cohort (as proxy for HA2 and/or NA imprinting epoch) not only to H7N9 but also H5N6 and H9N2 avian influenza, representing more varied conditions of zoonotic influenza relatedness to human subtypes of the past century.

We show homosubtypic NA imprinting likely further modulates the age-related risk of zoonotic H5N1 and H9N2, with implications for pandemic risk assessment and response.

       (Continue . . . )

While it is conceivable that some degree of community immunity to the NA of H5N1 might help blunt any future impact, it is far from guaranteed. Influenza A is a notoriously mutable virus, and H5 has swapped out its NA gene repeatedly over the years.

H5N8 dominated between 2014-2020, we continue to see spillovers of H5N6 viruses to humans in China, and over the past two years we've seen an increasing number of detections of H5N5 in mammalian wildlife in Canada and Northern Europe.

Emerg. Microbes & Inf: Unique Phenomenon of H5 HPAI Virus in China: Co-circulation of Clade 2.3.4.4b H5N1 and H5N6 results in diversity of H5 Virus

Cell Reports: Multiple Transatlantic Incursions of HPAI clade 2.3.4.4b A(H5N5) Virus into North America and Spillover to Mammals

Although it also carries an N1 neuraminidase gene, the older H5N1 clade circulating in Cambodia continues to produce an impressive 30%-40% case fatality rate. Granted, its N1 is structurally different from clade 2.3.4.4b, but we've already seen them reassort.

An H5N1 pandemic is far from assured, and we could easily be blindsided by something else. Predicting the next pandemic is a mug's game.  

But the more we learn about how past exposures to flu viruses affect our immune responses, the better equipped we'll be to deal with whatever comes next.