Friday, March 13, 2026

CDC MMWR: Interim Estimates of 2025–26 Seasonal Influenza Vaccine Effectiveness — United States, September 2025–February 2026

 
2025-2026 Flu Season - Credit CDC

#19,083

While the 2025-2026 flu season still continues (albeit on a downward trajectory), yesterday the CDC released their first estimate of this year's flu vaccine VE (Vaccine Effectiveness).  A final, revised, report should be issued in a few months.

In early November it became apparent that a new `drifted' H3N2 virus (subclade K) had recently emerged on the world stage, one which was antigenically distinct from this year's H3N2 vaccine strain. 

Early estimates (see UKHSA Preprint: Early Influenza Virus Characterisation and Vaccine Effectiveness in England in Autumn 2025, A Period Dominated by Influenza A(H3N2) Subclade K) suggested that the fall vaccine wasn't a total bust, but that it's VE would suffer. 

This is a scenario we've seen play out before - particularly with the H3N2 subtype (see 2017's The Enigmatic, Problematic H3N2 Influenza Virus) - which is more mutable, and more genetically diverse, than H1N1. 

The CDC Seasonal Flu Vaccine Effectiveness Studies webpage shows some of the variability of the flu vaccine VE over the years. While the dominant flu strain each year isn't shown, the lowest VE years were dominated by H3N2.

While most years we get a breakdown in VE between influenza A subtype (H1N1 and H3N2), this year H3N2 overwhelmed the flu season, and there was apparently insufficient data on H1N1 to break out those numbers. 

I've reproduced the summary and abstract of the MMWR interim report below. Follow the link to read it in its entirety.  

I'll have a bit more when you return.

Interim Estimates of 2025–26 Seasonal Influenza Vaccine Effectiveness — United States, September 2025–February 2026

Weekly / March 12, 2026 / 75(9);116–123

Patrick Maloney, PhD1,2; Emily L. Reeves, MPH1; Kristina Wielgosz, MPH1; Ashley M. Price, MPH1; Karthik Natarajan, PhD3,4; Malini B. DeSilva, MD5; Kristin Dascomb, MD, PhD6; Nicola P. Klein, MD, PhD7; Sara Y. Tartof, PhD8,9; Stephanie A. Irving, MHS10; Shaun J. Grannis, MD11,12; Toan C. Ong, PhD13; Zachary A. Weber, PhD14; Jennifer E. Schuster, MD15; Danielle M. Zerr, MD16; Marian G. Michaels, MD17; Julie A. Boom, MD18; Natasha B. Halasa, MD19; Mary A. Staat, MD20; Geoffrey A. Weinberg, MD21; Stacey L. House, MD, PhD22; Elie A. Saade, MD23; Krissy Moehling Geffel, PhD24; Manjusha Gaglani, MBBS25; Karen J. Wernli, PhD9,26; Vel Murugan, PhD27; Emily T. Martin, PhD28; Natalie A. B. Bontrager, MPH29; Marie K. Kirby, PhD1; Amanda B. Payne, PhD30; Fatimah S. Dawood, MD30; Ayzsa Tannis, MPH30; Heidi L. Moline, MD30; Sifang Kathy Zhao, PhD1; Katherine Adams, DrPH1; Jennifer DeCuir, MD, PhD1; Samantha M. Olson, MPH1; Jessie R. Chung, MPH1; Nathaniel Lewis, PhD1; Brendan Flannery, PhD1; Carrie Reed, DSc1; Shikha Garg, MD1; Sascha Ellington, PhD1; CDC Influenza Vaccine Effectiveness Collaborators (VIEW AUTHOR AFFILIATIONS)View suggested citation

Summary

What is already known about this topic?

CDC routinely monitors influenza vaccine effectiveness (VE). Annual influenza vaccination is available for all eligible persons aged ≥6 months.

What is added by this report?

Interim 2025–26 seasonal influenza VE estimates were derived from three U.S. VE networks. Among children and adolescents, VE was 38%–41% against influenza-associated outpatient visits and 41% against influenza-associated hospitalization. Among adults aged ≥18 years, VE was 22%–34% against influenza-associated outpatient visits and 30% against influenza-associated hospitalization.

What are the implications for public health practice?

Receipt of a 2025–26 influenza vaccine reduced the risk for influenza-associated outpatient visits and hospitalizations. These findings support CDC’s influenza vaccination recommendations.
Article PDF 

Abstract

In the United States, annual influenza vaccination has been recommended for all persons aged ≥6 months, including during the 2025–26 season. Interim influenza vaccine effectiveness (VE) estimates were calculated for patients with acute respiratory illness–associated outpatient visits and hospitalizations from three U.S. respiratory virus VE networks during the 2025–26 influenza season, using a test-negative case-control design.
  • Among children and adolescents aged <18 years, VE was 38%–41% against influenza outpatient visits and 41% against influenza-associated hospitalization.
  • Among adults aged ≥18 years, VE was 22%–34% against influenza outpatient visits and 30% against influenza-associated hospitalization.
  • Among children and adolescents, VE against influenza A ranged from 37% (against outpatient visits) to 42% (against hospitalization) across settings; among adults, VE against influenza A ranged from 30% (against hospitalization) to 34% (against outpatient visits) across settings.
  • Among children and adolescents, VE against influenza A(H3N2)–associated outpatient visits was 35% and against influenza A(H3N2)–associated hospitalization was 38%. VE against influenza B outpatient visits ranged from 45%–71% among children and adolescents and was 63% among adults.
Other estimates of VE were not statistically significant or were not reportable. Although interim influenza VE is lower during the 2025–26 influenza season than it was during recent influenza seasons, these findings demonstrate that influenza vaccination still provides protection against influenza. CDC recommends influenza vaccination; U.S. influenza vaccines remain available for persons aged ≥6 months.

        (Continue . . . )

Yesterday the FDA followed the WHO's lead and announced their recommendations for next fall's flu vaccine (see CIDRAP report FDA vaccine advisers recommend adding subclade K to fall shots), which swaps out all 3 flu strains. 

Despite offering only moderate protection, and being vulnerable to late-arriving `drifted' flu strains, I've gotten the flu shot every year for the past 20+ years, and have only once contracted the flu (summer 2009). 

Admittedly, I take other precautions, including wearing a mask in crowded indoor venues and using hand sanitizer.  But when combined with the flu vaccine, it has proven to be a very effective combination. 

Everyone has to make their own risk-reward calculation, of course. 
But given everything we've learned about influenzas' extrapulmonary impacts on the body (see Risk of Cardiovascular Events After Influenza), it seems a reasonable enough trade off to me. 

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Thursday, March 12, 2026

CDC Preprint: A Newly Emergent N1 Neuraminidase Associated with Clade 2.3.4.4b HPAI A(H5) Viruses in North America


 

#19,082

In the fall of 2024 - barely six months after the discovery of the `Bovine' B3.13 genotype of H5N1 circulating in U.S. dairy cattle - another genotype of H5N1 appeared in Canada and the Pacific Northwest - dubbed D1.1 - which very quickly became dominant in wild birds and rapidly swept eastward across the United States and Canada.

Although both B3.13 and D1.1 have spilled over into dozens of (primarily) agriculturally exposed humans, the bovine strain has produced mostly mild symptoms, while a few D1.1 patients saw severe (and even fatal) illness (see here, here, and here). 

The exact cause of B3.13's mild presentation remains unclear, but many researchers have posited that - since its N1 Neuraminidase gene is similar to that found in seasonal H1N1 -  many people may have some preexisting (albeit, limited) immunity to that genotype.

A few examples include:
Preprint: Cross-Reactive Human Antibody Responses to H5N1 Influenza Virus Neuraminidase are Shaped by Immune History

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

Two EID Journal Articles On Prior Immunity From A(H1N1)pdm09 Infection Against H5N1 (in Ferrets)

The D1.1 genotype, however, carries a different (North American lineage) N1 Neuraminidase, which may account for its ability to cause more severe illness. 

And in its opening months, it displayed brief, but worrisome, signs of antiviral resistance. 

Our first inkling of all of this came just over a year ago in Emerg. Microbes & Inf: Oseltamivir Resistant H5N1 (Genotype D1.1) found On 8 Canadian Poultry Farms, where Canada's PHAC and CFIA wrote:

Abstract

We report the detection of a clade 2.3.4.4b A(H5N1) reassortant virus with a neuraminidase surface protein derived from a North American lineage low-pathogenic avian influenza virus. This virus caused a widespread and ongoing outbreak across 45 poultry farms in British Columbia, Canada.

Isolates from 8 farms reveal a mutation in the neuraminidase protein (H275Y) that is exceptionally rare among clade 2.3.4.4b viruses (present in 0.045% of publicly available clade 2.3.4.4b isolates). NA-H275Y is a well-known marker of resistance to the neuraminidase inhibitor oseltamivir. We demonstrate that this substitution maintains its resistance phenotype on the genetic background of H5N1 clade 2.3.4.4b viruses.

Since then we've seen multiple spillovers of D1.1 into dairy cattle (Nevada, Arizona & Wisconsin), and some studies (see J.I.D.: Avian influenza virus A(H5N1) genotype D1.1 is better adapted to human nasal and airway organoids than genotype B3.13) have suggested D1.1 may be better suited to human biology than the `bovine'  strain. 

At this point it's worth noting that there are scores of other HPAI H5 genotypes in circulation  - both in North America and around the globe - many of which have yet to be fully (or even partially) characterized. 

But, of the H5 genotypes currently on our radar, D1.1 ranks pretty high on our watch list.  All of which brings us to a preprint from researchers at the CDC, which looks at what we currently know - and don't know - about this emergent genotype. 

I've reproduced the abstract, and an excerpt from the discussion. Follow the link to read the preprint in its entirety.  I'll have a postscript after the break.

Matthew J Wersebe, Nicole M Paterson, Norman Hassell, Xiao-yu Zheng, Benjamin J Rambo-Martin, Julia C Frederick, Kristine K Lacek, Amanda H Sullivan, Marie Kirby, Rebecca Kondor, Yunho Jang, Sabrina Schatzman, Han Di, C. Todd Davis
doi: https://doi.org/10.64898/2026.03.09.26347929
This article is a preprint and has not been certified by peer review


Abstract

We investigated the evolutionary history of the newly emergent neuraminidase (am4N1) associated with the D1.1 and D1.2 genotypes of highly pathogenic avian influenza A(H5N1) viruses in North America. 

Phylogenetic inference places am4N1 in a sister clade to Eurasian avian, swine, and human A(H1N1)pdm09 viruses and distinct from 1918, pre-2009 human seasonal, and classical swine A(H1N1) lineages. 

Am4N1 descends from diverse avian N1 genes endemic to the Americas. Phylodynamic analysis indicates a monophyletic am4N1 lineage with numerous introductions of viruses carrying the am4N1 gene likely originating from western Canada into the United States during emergence of the D1.1 and D1.2 genotypes.

The lineage has diversified and accumulated deletions in the stalk domain. Despite amino acid divergence, structural modeling shows conserved neuraminidase architecture in the globular head. Given its distinct ancestry and amino acid sequence, further studies are needed to assess cross-reactivity of antibodies from prior human A(H1N1)pdm09 infections.
(SNIP)
Pandemic preparedness countermeasures such as vaccines typically rely on comparing host antibody recognition via Hemagglutinin inhibition assays (HAI) as the HA mediates viral attachment and host cell entry and is the primary surface antigen. However, the NA plays a key role in influenza viral replication as well - allowing the release of progeny virions from infected cells [27, 36].

Neuraminidase activity is targeted by numerous pharmaceutical countermeasures including the widely prescribed oseltamivir which inhibits its enzymatic activity [37]. Currently, Neuraminidase inhibiting pharmaceuticals are stockpiled for the event of an influenza pandemic. 
Signore et al. [8] showed that am4N1 NAs isolated from Canadian chickens harbored an amino acid substitution at NA:H275Y, a known marker for resistance to oseltamivir and showed that the isolate with NA:H275Y had decreased  susceptibility to oseltamivir. 

This clade has not shown onward transmission in the samples analyzed here but continued surveillance for NA:H275Y is needed. Most am4N1 NAs do not carry this amino acid substitution and human isolates tested to date are inhibited well by NAI pharmaceuticals [38].

Another critical aspect of pandemic preparedness is fully understanding the genetic makeup and evolutionary history of pathogen threats. Here we provide a description of the phylogenetics and evolution of am4N1 NAs which have contributed to the ongoing epizootic in wild birds, infected numerous mammals, and caused two human fatalities to date. 

In addition, we use bioinformatic analysis to predict the structure of diverse NAs and determine how sequence identity changes may have functional implications for am4N1 NAs. Am4N1-like NAs are highly divergent from those previously associated with HPAI A(H5N1) viruses from clade 2.3.4.4b and are phylogenetically distant from NA genes that humans may have immunity to via vaccination and prior infection. 

Detailed studies describing the human antibody recognition of viruses with the am4N1 protein following seasonal influenza vaccination or infection are needed to fully understand the public health risk posed by D1.1 viruses and its derivate genotypes sharing this NA lineage. 
       (Continue . . . .)

We are now 18 months since the first detection of D1.1, yet there is still much we don't know about its impact, prevalence, or pandemic potential. Surveillance is spotty at best, and the public release of WGS (Whole Gene Sequencing) and antigenic characterization data continues to be limited.
Remarkably, the exact number of human infections with the D1.1 genotype is unknown, since only a subset (of the roughly 6 dozen) North American human cases have been fully characterized. 
A year ago, in Nature: Lengthy Delays in H5N1 Genome Submissions to GISAID. we saw the average delay in submitting sequences to GISAID was 7 months (228 days), with some countries taking nearly 2 years. 
And genetic sequences - when they are submitted to GISAID - are often devoid of crucial metadata (i.e. collection date, exact location, host-specific information, etc.), limiting their value to the scientific community.
While I'm sure there are legitimate logistical challenges involved, it is hard to believe this is the best we can do. 
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Wednesday, March 11, 2026

Viruses: Novel Reassortant H5N2 Highly Pathogenic Avian Influenza Viruses from Backyard Poultry in Mexico

 

#19,081

Influenza A's superpower is its ability to simultaneously infect a host with 2 or more strains, swap genetic material, and generate a new `hybrid' virus; a reassortant. This reassortment can generate new genotypes, or - if the HA or NA are swapped - a new subtype.

While flu viruses continually evolve slowly through antigenic `drift' - as we saw with H3N2 subclade K this past winter - truly large evolutionary jumps generally require reassortment (aka `Antigenic Shift').  

Most reassortants end up as evolutionary failures, but when they get it right, they can spark pandemics.  While rare, any virologist will tell you; `Shift happens.'

Twice in my lifetime (1957 & 1968) avian flu viruses did 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.

When H5N1 arrived in North America 4 years ago it immediately began to reassort with local LPAI viruses, and in the first year generated at least 100 distinct genotypes. Since then, we've seen:

This growing diversity of HPAI H5 can be seen everywhere the virus goes:

Due to limited surveillance and sharing of information, there are undoubtedly far more HPAI H5 reassortants circulating around the globe than we know. 

But today we get details on the recent emergence of HPAI H5N2 viruses - due to the reassortment of LPAI H5N2 and HPAI H5N1 - in backyard poultry across 3 Mexican states: Michoacán, Estado de México, and Ciudad de México.

This follows the announcement of the first known human infection with HPAI H5N2 (also in Mexico) last September. That was the third H5 case reported from Mexico since 2024, and the source of all three remain undetermined.


Notably, this study found two distinct genotypes of HPAI H5N2, which supports the idea that reassortment activity is ongoing. The newer - more complex genotype (from Nezahualcóyotl and Gustavo A. Madero outbreaks) - most closely matches the human H5N2 case mentioned above.

I've only reproduced the abstract and an excerpt from the conclusion. Follow the link to read it in its entirety.  I'll have a bit more after the break.
Novel Reassortant H5N2 Highly Pathogenic Avian Influenza Viruses from Backyard Poultry in Mexico
Mario Solís-Hernández1,*, Guillermo Orta-Pineda1,*, Carlos Javier Alcazar-Ramiro1, Montserrat Amaranta Velázquez-Vázquez1, Claudia Garnica-Rivera1,
Marisol Karina Rocha-Martínez2, Nadia Carrillo-Guzmán1, Ignacio Eliseo Tetla-Zapotitla2, Israel Tiburcio-Sánchez1 … Armando García-López1
Viruses2026, 18(3), 337;https://doi.org/10.3390/v18030337
9 March 2026

Abstract

Highly pathogenic influenza A viruses of the H5 subtype continue to diversify worldwide through mutation and genetic reassortment, generating novel variants with unpredictable consequences under the One Health approach. 

Between 2024 and 2025, five outbreaks of avian influenza A viruses were detected in backyard poultry across Michoacán, Estado de México, and Ciudad de México. We conducted molecular and genetic characterization of five highly pathogenic H5N2 viruses isolated from these events. All cases tested positive for influenza A virus and the H5 hemagglutinin, exhibiting high pathogenicity with intravenous pathogenicity index values ranging from 2.88 to 3.0.

 Whole-genome sequencing revealed novel reassortants containing hemagglutinin from Eurasian H5N1 clade 2.3.4.4b and neuraminidase from the endemic Mexican H5N2 lineage. The viral genome of the isolate from Michoacán contained six segments derived from Eurasian H5N1 viruses introduced into North America in 2021–2022, while nucleoprotein and neuraminidase originated from Mexican H5N2 viruses. 

In contrast, viruses from Estado de México and Ciudad de México contained five H5N1-derived segments and incorporated polymerase basic protein 1, nucleoprotein, and neuraminidase from low-pathogenic H5N2 viruses circulating in 2024. Phylogenetic analyses confirmed the emergence of a distinct H5N2 Mexican sublineage, providing evidence of active viral reassortment and local evolutionary processes in Mexico.
(SNIP)

5. Conclusions

This study reports the emergence of novel H5N2 reassortant viruses in central Mexico, resulting from interactions between highly pathogenic H5N1 clade 2.3.4.4b and endemic low-pathogenic H5N2 lineages. The distinct genomic constellations identified, ranging from early-stage reassortants to more complex combinations involving PB1, NP, and NA, demonstrate active viral ex🔜→→change within backyard poultry systems. 

These findings emphasize the critical role of informal production environments as ecological niches that facilitate reassortment and sustain viral diversity. Mutational patterns in HA and NA further reveal ongoing adaptation and selective pressures consistent with extended regional circulation. 

The emergence of these reassortants underscores the urgent need to strengthen genomic surveillance programs, particularly in regions where influenza lineages overlap and biosafety measures are limited. Continuous monitoring will be essential to assess the evolutionary trajectory, pathogenic potential, and epidemiological impact of these viruses, as well as their implications for poultry health, zoonotic transmission, and pandemic risk.

       (Continue . . . )


The first known human H5N1 infections (n=18) were reported in Hong Kong in 1997. Seventeen years later (in 2014) we saw the 1st Known Human Infection With H5N6 Avian Flu Sichuan Province, China, and 7 after that (2021) we saw the first human infections with H5N8 in Russia.
  
While worrying, this relatively slow progress - averaging > 10 years between each new subtype spillover - has been somewhat reassuring. 

In contrast, over the past 6 months we've seen two new HPAI H5 subtypes spillover into humans for the first time; H5N2 in Mexico and H5N5 in the United States.  

Moreover, the interval between each new H5 subtype spillover (17 yrs ➡ 7 yrs ➡ 4 yrs) continues to shrink.

While all of this could be a coincidence, it's a trend we shouldn't ignore. The greater viral diversity in the wild, the better the chance that one of these novel viruses will crack the code, and spark the next global health crisis. 

And with our continued reliance on limited (and mostly passive) surveillance systems, our first clue may only appear after hospitals begin filling up with patients. 

Again.


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Tuesday, March 10, 2026

Cell: Dynamics of Natural Selection Preceding Human Viral Epidemics and Pandemics


#19,080

We've a fascinating, albeit somewhat controversial, study published last week in Cell which questions whether whether animal viruses must undergo some form of special adaptation before they can spill over into humans.  

Obviously, we've looked at literally hundreds of spillovers (like Nipah, Ebola, H5Nx, Mpox, etc.) over the years, but the scientific consensus has been that these have been `flukes' -  and that these viruses would have to further adapt to pose a serious public health threat.  

As an example, we have a specific (and growing) watch list of `mammalian adaptations' (e.g. PB2 mutations like E627K, D701N, Q591K, and M631L and HA mutations like Q226L and E190D) that we look for in HPAI H5 (and other) influenza viruses.

Today's study suggests that - while these markers are still useful - many viruses with pandemic potential simply don't require prior-adaptation in order to jump species. 

 They just need opportunity. 

As to the above-mentioned controversy, the authors state in a UCSD press release that they found:

No evidence that SARS-CoV-2 was shaped by selection in a laboratory or prolonged evolution in an intermediate host prior to its emergence. That absence of evidence is exactly what we would expect from a natural zoonotic event.

Since I don't have a dog in this fight, I'll simply acknowledge the elephant in the room and move on. The press release summarizes their main findings:

The prevailing model of zoonotic emergence has often assumed that viruses must first acquire adaptive mutations before they can sustain human-to-human spread. To test that assumption, the research team analyzed viral genomes from outbreaks caused by influenza A virus, Ebola virus, Marburg virus, mpox virus, SARS-CoV and SARS-CoV-2. They focused on the evolutionary period immediately preceding human outbreaks, where any substantial pre-spillover adaptation should leave a detectable imprint.

Across these diverse viruses, the investigators found a strikingly consistent pattern: selection pressures before zoonotic emergence were indistinguishable from those acting during routine circulation in animal reservoirs. In other words, there was no evolutionary signal suggesting that these viruses were being “pre-adapted” for humans prior to their outbreaks. Instead, measurable changes in selection typically appeared only after sustained transmission began in people.

“From a broad epidemiological standpoint, our findings challenge the idea that pandemic viruses are evolutionarily special before they reach humans,” Wertheim said. “Rather than requiring rare, finely tuned adaptations in animals, many viruses may already possess the basic capacity to infect and transmit between humans. What matters most is human exposure to a diverse array of animal viruses.”

I've posted the link and summary below, but there is a lot more to unpack, so you'll want to read the report in its entirety.   I'll return with a bit more after the break.

Dynamics of natural selection preceding human viral epidemics and pandemics

Jennifer L. Havens 1 2 9, Sergei L. Kosakovsky Pond 3, Jordan D. Zehr 3 4, Jonathan E. Pekar 1 5 6, Edyth Parker 7, Michael Worobey 8, Kristian G. Andersen 7, Joel O. Wertheim 6S 
https://doi.org/10.1016/j.cell.2026.02.006 Get rights and content
Under a Creative Commons license
 
Highlights
  • Viral adaptation is not a necessary precursor to outbreaks of novel zoonotic viruses
  • Selection signatures on SARS-CoV-2 were unchanged until its emergence in humans
  • Laboratory and gain-of-function passage produce distinct evolutionary signatures
  • 1977 influenza virus reemergence preceded by evolution consistent with laboratory passage
Summary

Using a phylogenetic framework to characterize natural selection, we investigate the hypothesis that zoonotic viruses require adaptation prior to zoonosis to sustain human-to-human transmission.
Examining the zoonotic emergence of Ebola virus, Marburg virus, mpox virus, influenza A virus, and SARS-CoV-2, we find no evidence of a change in selection intensity immediately prior to outbreaks in humans compared with typical selection within reservoir hosts.
We found a change in selection on SARS-CoV in an intermediate host.
We conclude that extensive pre-zoonotic adaptation is not necessary for human-to-human transmission of zoonotic viruses. In contrast, the reemergence of H1N1 influenza A virus in 1977 was preceded by a shift in selection intensity, consistent with the hypothesis of passage in a laboratory setting.
Holistic phylogenetic analysis of selection regimes can be used to detect evolutionary signals of host switching or laboratory passage, providing insight into the circumstances of past and future viral emergence.
        (SNIP)
In this study, we have distinguished epidemics that are characterized by viruses that evolved primarily under a selection regime in the natural host reservoir prior to emergence from those that did not. Humans are constantly exposed to animal viruses.58,71 However, most of these exposures do not result in ongoing outbreaks with human-to-human transmission, due to low fitness of the virus or lack of sufficient transmission opportunities (such as in rural communities).72
In recent zoonotic epidemics with sustained human-to-human transmission, we found no detectable change in selection preceding the epidemics. Applying multi-region RELAX to the stem of novel viral outbreaks is a tool that we can apply to future outbreaks to rapidly assess the possibility of evolution in an intermediate host or a laboratory setting, compared with zoonosis directly from the natural host reservoir. Increased sampling of viruses in reservoir species will improve the power of approaches for investigating future zoonotic outbreaks.

       (Continue . . . )


While we comfort ourselves with the notion that we'd see distinct changes in the H5Nx virus that would telegraph when it was ready for prime time, today's study warns that such changes may not be necessary for the virus to jump to humans. 

The authors wrote: `These findings challenge the model in which zoonotic viruses must progressively evolve the ability to sustain human-to-human transmission.'

In 2024, after nearly 30 years of continual circulation in Mexico, the LPAI H5N2 virus abruptly jumped to a 58-year-old immunocompromised patient - who had been bedridden for weeks - and had no obvious exposure risks. 

The virus was a > 99% match with an avian LPAI H5N2 isolate from Texcoco, State of Mexico (2024), and showed no obvious signs of viral adaptation. 
 
What series of events led to this first recorded human infection with LPAI H5N2 remains a mystery, but serological studies of poultry workers suggest that these types of infections probably happen more often than we know (see Taiwan: Three Poultry Workers Show H5N2 Antibodies).

While these spillovers have thus far failed to spread efficiently in humans, each spillover is another opportunity for the virus to better adapt to a human host. 

Although we might see the next pandemic coming, our continued resistance to greatly increasing surveillance and testing of wildlife and livestock, and of humans that have routine exposure to those animals or their environments, makes any early warning far less likely. 

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Monday, March 09, 2026

South Korea: MAFRA Investigation Into Biosecurity Lapses on HPAI Affected Poultry Farms

 

#19,079

Despite more than 2 decades of dealing with extensive bird flu outbreaks, and numerous warnings to farmers (see here, here, here) on the importance of maintaining strict biosecurity, once again this winter South Korea finds itself struggling to contain HPAI H5. 

Even before this year's avian flu season began, South Korea Conducted A 19-day, Nationwide, Mock-Training Exercise to Prepare for Zoonotic Influenza, immediately followed by South Korea: MAFRA Conducts A Preemptive Virtual Quarantine Exercise (CPX). 

In November, South Korea MAFRA Ordered Strengthened Quarantine Measures After 3 HPAI H5 Subtypes (H5N1, H5N6, H5N9) Detected In Wild Birds, and issued stern warnings to farms over lapses in biosecurity South Korea: MAFRA Identifies Biosecurity Breaches On HPAI Infected Poultry Farms).

In early January MAFRA described this year's avian flu season as particularly challenging (see below) and announced Special Quarantine Measures Implemented for one Month to Prevent the Spread of HPAI (now extended to March 31st):

This winter season, for the first time in Korea , three types of viruses ( serotypes : H5N1, H5N6, H5N9) were detected in wild birds and poultry farms, and in particular, the highly pathogenic avian influenza virus ( serotype H5N1) confirmed in Korea this winter season was confirmed to be more than 10 times more infectious than in previous years, making the situation very serious with a higher risk of additional outbreaks than ever before .

Today MAFRA has released an eye opening report on their investigation into the biosecurity practices found on 50 of this year's 53 infected poultry farms, which  reports 70% of these farms had at least one serious violation.

  • 70%: No disinfection or protective clothing for people entering farms
  • 68%: Vehicles entering/exiting farms not disinfected
  • 66%: Poor overall sanitation management
  • 62%: Workers not using farm-specific clothing/footwear
  • 48%: Inadequate barriers to prevent entry of wild animals

Although it is a fairly lengthy report, I've posted the full translation below.  I'll have a brief postscript after the break. 


2026.03.09 13:05:00 Avian Influenza Prevention Division, Quarantine Policy Bureau
The Central Disaster and Safety Countermeasures Headquarters for Highly Pathogenic Avian Influenza ( Director Song Mei-ryeong, Minister of Agriculture, Food and Rural Affairs , hereinafter referred to as the Central Disaster and Safety Countermeasures Headquarters ) announced that the epidemiological investigation conducted so far on poultry farms where highly pathogenic avian influenza occurred this winter has revealed numerous inadequate quarantine measures , and that quarantine management has been strengthened to prevent further outbreaks due to the risk of the outbreak due to the full-scale northward migration of winter migratory birds .
1. Analysis of the situation

This ('25/'26 season ) , 53 cases of highly pathogenic avian influenza have occurred in poultry farms and 62 cases in wild birds as of March 9th .
* Poultry farm occurrence status ( total 53 cases ): 13 cases in Gyeonggi , 9 in North Chungcheong , 9 in South Chungcheong , 4 in North Jeolla , 10 in South Jeolla , 5 in North Gyeongsang , 1 in South Gyeongsang , 1 in Gwangju , 1 in Sejong

** Status of wild bird detection ( total 62 cases ): Gyeonggi 6 , Gangwon 8, Chungbuk 1, Chungnam 14, Jeollabuk-do 6, Jeollanam-do 7 , Gyeongbuk 3, Gyeongnam 5, Jeju 4, Seoul 4, Busan 2, Incheon 1, Gwangju 1
This winter, for the first time in Korea, three types of highly pathogenic avian influenza viruses ( serotypes : H5N1, H5N6, H5N9) were detected in wild birds and poultry farms . The Animal and Plant Quarantine Agency evaluated the infectivity and pathogenicity of the domestic poultry virus (H5N1) and found that the infectivity was more than 10 times higher than in previous years. As the disease can easily spread even with a small amount of virus, more thorough quarantine management such as disinfection and access control is needed than ever before .
According to the results of the February migratory bird population survey, there are a large number of birds, 1.33 million, and highly pathogenic avian influenza has been continuously occurring in poultry farms and wild birds recently . Considering the cases of outbreaks during the migratory bird migration period since March, there is a risk of additional outbreaks. Therefore , poultry farms should strengthen their own quarantine and disinfection , and if they have any suspicious symptoms , they should quickly report them to quarantine authorities .
* Farm (53 cases ): (September ) 1 case → (October ) 1 case → (November ) 4 cases → (December ) 22 cases → ( January ) 10 cases → (February ) 13 cases → ( March ) 2 cases

Migratory birds (62 cases ): (September ) 0 cases → (October ) 2 cases → (November ) 11 cases → ( December ) 10 cases → (January ) 19 cases → (February ) 20 cases → ( March ) 0 cases
2. Results of interim epidemiological investigation and quarantine inspection of the outbreak farm

< Results of epidemiological investigation of the outbreak farm >

Interim epidemiological investigations of the 50 confirmed outbreak farms to date have revealed that many farms are not complying with basic quarantine guidelines . Accordingly, the Central Disaster and Safety Countermeasures Headquarters plans to strictly enforce administrative sanctions, such as fines, and reductions in compensation for livestock disposal, in accordance with the Livestock Infectious Disease Prevention Act, against farms that violate relevant regulations .
* According to the “ Standards for Payment and Reduction of Compensation in Appendix 2 of the Enforcement Decree of the Livestock Infectious Disease Prevention Act, ” the farm where the disease occurred will basically receive a reduction of 20 % of the livestock evaluation price , and if any insufficient quarantine measures are found, the compensation will be reduced for each applicable item.






During the special quarantine period for highly pathogenic avian influenza (AI) (October 1, 2025 - February 13, 2026) , the Animal and Plant Quarantine Agency mobilized its on-site inspection team ( 40 people in 20 teams ) to inspect the quarantine management compliance of poultry farms. As a result , a total of 59 farms were found to have violated the quarantine management and were issued certificates . Of these , 43 (72.9%) were laying hen farms, accounting for more than two -thirds .
* 59 farms in violation : 43 laying hens , 4 broilers , 3 each of meat ducks and broiler breeders , 2 laying breeders , 1 each of breeders , native chickens , hatcheries , and livestock vehicles

In the case of the laying hen farm with the most violations ( No. 43 ) , the number of violations was 57 , and 24 cases * (42.1%) of them were found to be violations of the “ Administrative Orders and Notices, ” which are the entry control and quarantine standards for poultry farms that must be followed during the special quarantine period . Among them , the violation of “ Failure to perform Stage 2 disinfection of vehicles entering and exiting the farm ” (13 cases ) was confirmed as the most common .

* 13 cases of failure to implement two- stage disinfection (1st stage disinfection with vehicle disinfection machine → 2nd stage disinfection of vehicle wheels, etc. with high-pressure sprayer ) upon entry of livestock vehicles into farms, 10 cases of violation of prohibition of entry into farms by egg transport vehicles , vaccination team vehicles , and poultry loading/unloading crew personnel transport vehicles , etc.

3. Strengthening quarantine measures

The Central Disaster and Safety Countermeasures Headquarters will strengthen quarantine measures as follows to prevent further outbreaks due to migratory birds moving north .

First , in order to prevent further outbreaks in laying hens across the country, one-on-one dedicated officers will be assigned to laying hens with more than 50,000 hens nationwide by March to manage vehicles and people entering and exiting the farms . In particular, control posts installed at densely populated poultry farms and large laying hens with more than 200,000 hens will be intensively inspected to ensure compliance with quarantine measures, such as disinfection of vehicles entering the farms .

Second , the Ministry of Agriculture , Food and Rural Affairs, the Ministry of Public Administration and Security , and provincial/ provincial governments will jointly inspect the quarantine situation in 32 cities and counties at risk during the migratory bird migration season (until March 17) and manage any deficiencies by supplementing them .

* ( Gyeonggi area ) 7 including Anseong , Hwaseong , Pyeongtaek , and Pocheon , ( Chungcheong area ) 8 including Eumseong , Asan , Cheonan , and Sejong , ( Jeolla area ) 12 including Gimje , Iksan , Naju , and Muan , ( Gyeongsang area ) 5 including Uiseong , Bonghwa , and Changnyeong

Third , to eliminate viruses during the risk period, the period from March 5 to March 14 will be designated as “ National Disinfection Week ,” and disinfection will be carried out at least twice a day on farms , livestock facilities , vehicles, etc.

Fourth , in cooperation with producer groups, etc., we will promote and guide the ' Quarantine Management Reinforcement Campaign * ' targeting poultry farms for one month in March so that quarantine rules can be thoroughly implemented on site .

* Key initiatives : ① Change your boots when entering and exiting the barn , ② Clean and disinfect , ③ Work on the old books

4. Requests

The Ministry of Agriculture, Food and Rural Affairs' Director of Quarantine Policy, Dong-sik Lee , said, " As a result of the epidemiological investigation into poultry farms where highly pathogenic avian influenza occurred this winter , it was confirmed that most farms were not properly following basic quarantine rules, such as not disinfecting or wearing quarantine clothing ." He requested , " The relevant local governments should take strict measures in accordance with relevant regulations and repeatedly provide guidance and education so that poultry farms can be vigilant and make every effort to manage quarantine at the farm level . "

In addition , he emphasized again that “ the current situation is very critical as highly pathogenic avian influenza virus is continuously being detected in wild birds, ” and that “ poultry farms should thoroughly follow basic quarantine rules such as two- stage disinfection of vehicles entering the farm and changing boots with the mindset of ‘ I protect my own farm ’ to prevent further outbreaks . ”

Although South Korea's bird flu problem may have already peaked for the season, it is not unusual to see sporadic outbreaks extend into May or even June. It doesn't help that South Korea is also dealing with concurrent outbreaks of ASF and FMD. 

Repeated assertions that this year's avian flu is `10 times more infectious' are worrisome, but difficult to quantify. Multiple outbreaks of H5N9 (see South Korea: H5N9 Rising) are more tangible, and equally concerning. 

While it appears that some (perhaps, much) of South Korea's current avian flu woes can be attributed to lapses in farm biosecurity, it is possible they are also dealing with a more challenging wave of HPAI. 

If that turns out to be true, then the rest of the world could find themselves facing similar challenges next fall. 

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Sunday, March 08, 2026

Nature Comms: Mapping Global Avian Influenza Risk Patterns Through Waterbird Activity Entropy

 

#19,078

During the latter half of the 20th century Asia - and China in particular - had earned the reputation of being the `cradle of influenza', and was considered the most likely source of the next pandemic virus.

While ignoring the 1918 outlier, the last 2 pandemics of the last century (1957 & 1958) had both emerged from that part of the world, and in 1996 a new novel flu threat - H5N1 - had briefly emerged in Hong Kong. 

Over the past quarter century China/Asia has served as the launching pad for a variety of novel flu viruses (HPAI H5N1, H5N6, H5N8, LPAI/HPAI H7N9 . . among others), along with both SARS-CoV and SARS-CoV-2 (COVID). 

But there have been notable exceptions; the 2009 H1N1 pandemic emerged from North American pigs, MERS-CoV was first detected on the Arabian peninsula (although it likely came from camels imported from Africa), and we've seen other threats - like Mpox and Ebola - emerge from Africa as well. 

While it is unlikely there will ever be a one-size-fits-all-viruses model, researchers continue to try to find ways to predict where the next pandemic virus will come from, in hopes that targeted surveillance might help contain it - or at least provide early warning. 

In 2013's EID Journal: Predicting Hotspots for Influenza Virus Reassortment, we looked at a study that identified 6 key geographic regions where influenza A reassortments were mostly likely to emerge. As you might expect, high on their list was Eastern mainland China.

Potential geographic foci of reassortment include the northern plains of India, coastal and central provinces of China, the western Korean Peninsula and southwestern Japan in Asia, and the Nile Delta in Egypt.

Just two weeks after this study was published, China announced the first human cases of H7N9 (see China: Two Deaths From H7N9 Avian Flu), which was to herald the start of a 5-year battle against the virus. 
Since then, we've seen a number of attempts to identify `hotspots' for viral spillovers. 

Almost exactly 4 years before COVID-19 emerged, we looked at a study of potential hotspots for the emergence of novel bat viruses (see Study: Hotspots For Bat To Human Disease Transmission).

This study cited West Africa, sub-Saharan Africa and Southeast Asia as being the most likely sources for a bat-borne pandemic.

For novel influenza A viruses, wild migratory birds have driven most of its global spread and spillovers into poultry, small mammals, and livestock (including cattle).  

While originally thought largely limited to aquatic birds (Anseriformes), in recent years HPAI's host range has greatly expanded (see DEFRA: The Unprecedented `Order Shift' In Wild Bird H5N1 Positives In Europe & The UK).


Last month, in Nature Comms: Assessing HPAI-H5 Transmission Risk Across Wild Bird Migratory Flyways in the United States, we looked at a study that mapped the spillover risks of HPAI H5 in the United States. 

Quite unexpectedly, Strigiformes (owls) had the strongest transmission capacity, with an R0 of 3.164. Previously owls (and raptors in general) had been thought highly susceptible, but likely to succumb before spreading the virus. Anseriformes (waterfowl), surprisingly, had the weakest transmission capacity, with an R0 of 0.992.

Today we've another study that uses migratory waterbird tracking - albeit on far more ambitious global scale - to map global risk patterns for HPAI  spillover to humans, cattle, and poultry. 

Using citizen-scientist observation data (e.g., GBIF or eBird) and machine learning, the authors created species distribution models (SDMs) to map, on a monthly basis, where 779 waterbird species can be found worldwide.

From this, they created a `waterbird activity entropy' (WAE) index number, which they compared to known spillovers in those regions. They found that a higher WAE number correlated strongly to more spillovers. 
Finally, they combined WAE numbers with maps of human, cattle, and poultry density to identify potential `hotspots', where spillovers would be most likely, and which could benefit most from surveillance and biosecurity measures. 

As the map above illustrates, they cite four large regions as potential hotspots for HPAI spillover" the USA, the European Union, China, and India.  They do, however, point out limited surveillance in sub-Saharan Africa.

The authors write:
Notably, the AIV exposure hotspots in the USA, EU, China, and India contain 52% of the globally exposed human population, 41% cattle, and 51% poultry.
Despite reporting <1% of global cases, sub -Saharan Africa contains >300 Mha of hotspots area (15% globally ), highlighting considerable surveillance gaps.
This WAE -based framework enhances AIV risk assessment by incorporating waterbird residency time, offering critical insights for anticipating AIV emergence and improving surveillance.
This is a fascinating study, which provides a unique reusable global map of waterbird-driven avian flu hotspots, which will hopefully help countries prioritize surveillance, and allocate resources, in our ongoing battle against avian flu.

I've only posted the abstract and some excerpts. Follow the link to read it in its entirety.  You'll find a number of detailed maps at the bottom of the PDF file.


Mapping global avian influenza risk patterns through waterbird activity entropy
Yuzhe Li, Yuxin Qiao, Yue Zhan, Jinwei Dong, Mariëlle van Toor, Jonas Waldenström, A. Townsend Peterson, Qiang Zhang, Zhichao Li, Weipan Lei, Fanshu Du, Juan Pu, Dayan Wang & Xiangming Xiao
Nature Communications , Article number: (2026) Cite this article

       PDF 

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Abstract
Avian influenza viruses (AIV) pose a major zoonotic threat with pandemic potential. Waterbirds facilitate AIV spillovers into farm animals and humans through exposure and virus reassortment.
Here, we propose waterbird activity entropy (WAE), an indicator of waterbird activity intensity based on monthly distributions of 779 species worldwide. WAE demonstrated high explanative power (AUC = 0.87 ± 0.001) for global avian influenza cases, particularly for H5N1, revealing the potential of WAE for identifying AIV exposure hotspots which cover 14% of global land area.
Notably, the AIV exposure hotspots in the USA, EU, China, and India contain 52% of the globally exposed human population, 41% cattle, and 51% poultry. Despite reporting <1% of global cases, sub-Saharan Africa contains >300 Mha of hotspots area (15% globally), highlighting considerable surveillance gaps.
This WAE-based framework enhances AIV risk assessment by incorporating waterbird residency time, offering critical insights for anticipating AIV emergence and improving surveillance.
Introduction 

The last four influenza pandemics (in 1918, 1957, 1968, and 2009) originated primarily from avian influenza virus (AIV) strains or genetic reassortment of AIV 1,2. Most spillover events among domestic animals and humans are related to various AIVs carried by bird species associated with wetlands , aquatic , and marine habitats 3,4 (hereafter waterbirds).
These various and recurring reassortments, coupled with frequent interactions between wild waterbirds and domestic animals, facilitate the virus ’s ability to cross between diverse host species 5,6, including wild and domestic birds, mammals, and occasionally humans 7,8 . For example, highly pathogenic avian influenza (HPAI) subtype H5N1 viruses have rapidly expanded their host range among waterbirds (especially long -distance migratory seabird and shorebird species) in recent years , increasing the risk of cross -continental spreading of emerging AIVs 3,9 . Therefore, identification of waterbird diversity and activity is significant, with a high risk of AIV spillover from natural ecosystems
        (SNIP)

As waterbirds are the primary AIV reservoir host 4 , this study provides an exposure risk analysis framework that considers the effects of migrating waterbirds in the context of climate and land use status. This framework enables a more accurate and balanced assessment of avian influenza risk, particularly in developing countries with limited surveillance resources. By addressing these interconnected factors, this study aligns with the One Health strategy, which considers different interfaces among waterbirds, poultry, cattle, and humans 38 , to predict and manage AIV risk more effectively in the future.

       (Continue . . . )

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