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

 

#19,081

Influenza A's superpower is its ability 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:

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

• In the fall of 2024 we saw 3 new genotypes emerge (D1.1, D1.2, D1.3), with D1.1 producing more severe illness in humans. 

• We continue to see scattered reports of HPAI H5N5 in birds and mammals in Europe & Canada, and the the United States, and last fall we saw the first confirmed (and fatal) human infection.

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

• South Korea is currently battling H5N1, H5N6, and H5N9. 

• Europe has their own distinct set of HPAI genotypes 

• A little over a year ago, in  Emerg. Microbes & Infections: Emergence of a Novel Reassortant HPAI Clade 2.3.4.4b A(H5N2) Virus, 2024, we looked at the emergence of a novel HPAI H5N2 virus in the Middle East. 

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.

• The first occurred in April of 2024 (see Mexico announced the death of a 58-year-old man) when a patient - who also suffered from serious comorbidities - tested positive for LPAI H5N2, becoming the first laboratory-confirmed human case of influenza A(H5N2) infection reported globally.

• A year later (April 2025), a 3-year old girl from Durango State died following an H5N1 infection (see WHO DON Update On Mexico's Fatal H5N1 Infection).

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.

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. 

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. 

Strict measures, including reductions in compensation, will be taken after identifying numerous farms where highly pathogenic avian influenza outbreaks have occurred and quarantine deficiencies have been identified.

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. 

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 . . . )

California DPH Advice to Public After H5N1 Detected in Elephant Seals

Credit Wikipedia

#19,077 

Ten days ago in  California: Background on the Outbreak of H5N1 in Elephant Seals at Año Nuevo Natural Reserve, we looked at the first reports of the detection of HPAI H5 in North American Elephant Seals.  

We also reviewed the devastating outbreaks previously reported in South America, and looked back at several studies on its increasing transmission among marine mammals (see here, here, and here). 

The initial report announced that 7 weaned seal pups had tested positive, after a small number of seals (later described by media as ~ 30) showed signs of illness (abnormal respirations, tremors, and neurological symptoms).

Disappointingly, we still don't have any publically released information on the genotype - or any other genomic information - beyond the subtype (reportedly H5N1).

According to their own documentation, a national reference lab like the NSVL should  be able - assuming they received viable, high quality samples - to sequence a priority novel flu virus in less than a week.

But in actual practice (see Nature: Lengthy Delays in H5N1 Genome Submissions to GISAID), the public release of data often takes weeks or even months. 

Official updates have been noticeably scant since the original announcement, but last night the California Department of Public Health published their first communications on this event, where they urge the public to be extra cautious around marine mammals and wild birds. 

CDPH Urges Public to Avoid Sick or Dead Marine Mammals and Birds Along California Coast

​March 6, 2026
NR26-010

Bird flu detected in elephant seal pups at Año Nuevo State Park; risk to public remains very low 

but officials urge caution 

What You Need to Know: H5N1 bird flu has been confirmed for the first time in northern elephant seal pups at Año Nuevo State Park​ in San Mateo County. While the risk to the general public remains very low and there is no evidence of seal‑to‑human transmission, CDPH urges people to avoid contact with sick or dead wildlife, including dead birds, to limit the potential transmission of bird flu to humans. Local, state, federal and academic partners continue to monitor and test wildlife to understand the scope of the incident. 

SACRAMENTO – The California Department of Public Health (CDPH) is urging the public to avoid contact with dead or distressed marine mammals and wild birds along the California coast after H5N1 bird flu, also known as highly pathogenic avian influenza (HPAI), was confirmed in weaned northern elephant seal pups at Año Nuevo State Park in San Mateo County. Wildlife workers are closely monitoring nearby beaches in San Mateo and Santa Cruz counties and conducting additional surveillance from Sonoma to San Luis Obispo County to better understand the possible spread of this disease.  ​

These findings represent the first documented cases of bird flu in northern elephant seals and the first detection of the virus in any marine mammal in California. As a precaution, California State Parks has closed key areas and cancelled public tours at Año Nuevo State Park for the remainder of the season to protect the animals and minimize the potential spread of disease.

“While the detection of bird flu in these young seals is concerning, it also shows that our surveillance systems are functioning as intended,” said Dr. Erica Pan, CDPH Director and State Public Health Officer. “The risk to the general public remains very low, but Californians can protect themselves and their pets by avoiding contact with sick or dead marine mammals or birds, keeping pets on a leash near beaches, and respecting area closures. CDPH will continue to work closely with local, state, federal and academic partners to monitor this situation, support safety for workers who may be exposed, and provide updates as more information becomes available.” 

What Californians Can Do: Avoid Contact with Wildlife 

Bird flu is a disease that has the potential to spread between animals and people, including pets. Although the risk of infection to the general public remains very low and there is no evidence of seal-to-human transmission, beachgoers should not touch live or dead marine mammals or birds or allow pets to approach these wild animals.  

CDPH guidance for the public: 

• Stay 150 yards away from elephant seals and all wild marine mammals and seabirds whenever possible. 
  

• Keep children and pets away from sick, injured or dead wildlife. 
  

• Do not approach, touch or attempt to assist marine mammals or seabirds, as this can spread disease and cause harm to both animals and people. 
  

• Transporting potentially sick wildlife to a rehabilitation center, veterinary clinic or other animal facility can increase exposure risk. Always contact the facility first​ for guidance and to determine if the animal should be collected. 
  

• Report sightings of sick, injured or dead marine mammals to the NOAA West Coast Marine Mammal Stranding Hotline: (866) 767‑6114. 
  

• Report sick or dead birds to the California Department of Fish and Wildlife. 
  

CDPH recommendations for wildlife workers:  

• Wear appropriate personal protective equipment (PPE) including gloves, eye protection and respiratory protection when working with sick or dead marine mammals.  
  

• Report any influenza-like symptoms after exposure to your local health department.  
  

• Seek testing if any symptoms develop within 10 days post-exposure. Persons with influenza (either regular seasonal influenza or bird flu) may be eligible for antiviral treatment to reduce disease severity.   
  

• If you’re not feeling well after a possible exposure: 
  

• Stay home, rest, and avoid contact with others except to get medical care. If you seek care for symptoms, notify your healthcare provider of your potential exposure to bird flu before or immediately on arrival. 
  

• Wear a mask indoors around other people and when entering any healthcare facility. 
  

• Wash your hands often (or use hand sanitizer with at least 60% alcohol if soap and water aren’t available). ​
  

Bird flu infections in people are rare, but infection can occur if the virus enters a person’s eyes, nose or mouth, or is inhaled during close unprotected contact with infected animals or by touching contaminated surfaces and then touching the eyes, nose or mouth. Pets such as dogs and cats may also be at risk of illness if they interact with infected wildlife. 

What CDPH is Doing: ​

CDPH is actively coordinating with California State Parks, the California Department of Fish and Wildlife, NOAA Fisheries, UC Davis, UC Santa Cruz, The Marine Mammal Center and the US Department of Agriculture to monitor and respond to incidents involving sick and dead elephant seals and other marine mammals. 

CDPH is supporting and advising local health departments with monitoring exposed personnel, providing appropriate personal protective equipment (PPE) and testing when needed, and ensuring public health and wildlife safety. Surveillance of wildlife in coastal areas has increased, and CDPH continues to monitor statewide influenza activity for any signs of bird flu in humans. 

Incident Timeline 

Initial signs of illness were observed in seal pups on February 19–20, when researchers noted weakness, tremors, seizures, abnormal neurological behavior and sudden death in some animals. Samples collected from sick and deceased pups tested positive for influenza A and were subsequently confirmed as H5N1 by the USDA National Veterinary Services Laboratories. 

With the spring northbound migration of birds now firmly underway, we've seen Several States Warn On Contact With Wild Birds/Mammals in recent weeks.  

While the public remains largely apathetic to the threat of HPAI (see Two Surveys (UK & U.S.) Illustrating The Public's Lack of Concern Over Avian Flu), the reality is the risks - while still fairly low - continue to increase. 

Making the above advice very much worth heeding. 

IJID: Lack of Respiratory Droplet Transmission of Two Recent Human Influenza A(H5N1) Viruses in Female Ferrets

 

#19,076

Today we've a study that reminds us how much we've yet to learn about what it takes for a novel zoonotic virus - like HPAI H5Nx - to turn into a genuine pandemic threat.  

First, a bit of history.

In the months following the discovery of first human infection with the Bovine B3.13 H5N1 virus (aka TX/37) in March of 2024, we saw a number of conflicting reports on the virulence and transmissibility of the HPAI virus in ferrets (see CDC: Updated Results On Texas H5N1 Virus In Ferrets).

Differences in methodology, equipment used, and endpoints, the host source (human vs bovine), viral evolution during isolation (cell culture vs eggs), and the use of a relatively small number of test animals all could have contributed to these mixed results.  

A reminder that no study design is perfect, that research is often incremental, and that we should view each new finding in the context of what has previously been reported by others.   

I mention all of these limitations because today's study, once again, provides some unexpected results. 

Researchers at the Kawaoka lab at the University of Wisconsin-Madison, along with international partners took two human isolates (1) B3.13 from a Dairy Worker in Michigan (MI90) and (2) a D1.1 from the B.C. adolescent (BC2032) who was critically ill, and tested their transmissibility in female ferrets. 

• Interestingly, the B3.13 virus (MI90) - which only caused mild conjunctivitis in its human host - caused severe disease, extra-respiratory spread, and was lethal in test ferrets.

• While the D1.1 virus (BC2032) - which put a teenage girl on ECMO - produced milder illness and no lethality in ferrets. 

• And neither virus transmitted via respiratory droplets in ferrets.

In addition to these non-intuitive findings, the authors also report that previous studies found the D1.1 (BC2032) strain led to 100% lethality in ferrets, while earlier studies found the MI90 strain caused `. . . sub-lethal disease in ferrets, with respiratory droplet transmission detected in 50% of naïve exposed animals.'

As we've discussed often, we have only a partial understanding of what genetic changes are needed to increase the virulence, transmissibility, or host range of a novel influenza A virus like HPAI H5. 

Scientists often look for a handful of known amino acid changes (e.g. PB2 mutations like E627K, D701N, Q591K, and M631L and HA mutations like Q226L and E190D) which may favor mammalian adaptation, but new ones (see Sci. Adv.: PB2 and NP of North American H5N1 Virus Drive Immune Cell Replication and Systemic Infections) continue to be discovered.

And many minor, seemingly innocuous genetic changes - when stacked in the right combination - can greatly increase or decrease, their impact. 

Exactly what part these (and other) factors may have played in today's unexpected results remains to be seen. I've just posted the abstract, and some brief excerpts, so follow the link to read the study in its entirety. 

I'll have a brief postscript after the break.

Lack of Respiratory Droplet Transmission of Two Recent Human Influenza A(H5N1) Viruses in Female Ferrets

Tong Wang 1, Chunyang Gu 1, Lizheng Guan 1, Asim Biswas 1, Tadashi Maemura 1, Hassanein H. Abozeid 1 2, Peter J. Halfmann 1, Gabriele Neumann 1, Amie J. Eisfeld 1, Yoshihiro Kawaoka 1 3 4 5 
https://doi.org/10.1016/j.ijid.2026.108514 Get rights and content
Under a Creative Commons license

 

Highlights

• Two human clade 2.3.4.4b H5N1 viruses (B3.13 and D1.1) were tested in ferrets.

• MI90-H5N1 (B3.13) caused severe disease, extra-respiratory spread, and lethality.

• BC2032-H5N1 (D1.1) caused milder disease with no lethality in ferrets.

• Neither virus transmitted via respiratory droplets in ferrets.

• Respiratory droplet transmissibility of clade 2.3.4.4b H5N1 viruses appears variable.

Abstract

Background

Clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) (HPAI H5N1) viruses are widespread globally and have transmitted from birds to dairy cattle at least four times in the United States, including once by a genotype B3.13 virus and three times by genotype D1.1 viruses. Despite their prevalence and known ability to infect humans, only a few studies have examined respiratory droplet transmission capabilities of clade 2.3.4.4b viruses in mammalian models of influenza infection.

Methods

Here, we assessed respiratory droplet transmission of two recent human clade 2.3.4.4b HPAI H5N1 viruses – A/Michigan/90/2024 (‘MI90-H5N1’), a B3.13 isolate, and plaque-purified A/British Columbia/PHL2032/2024 (‘BC2032-H5N1’), a D1.1 isolate – in the ferret model.

Findings

We found that MI90-H5N1, in contrast to earlier findings, causes severe disease and partial lethality in ferrets, with virus spread to extra-respiratory organs and no respiratory droplet transmission. BC2032-H5N1 caused less severe disease with no lethality in ferrets and, consistent with a recent report, failed to transmit via respiratory droplets.

Interpretation

Together with other reports, our results suggest that respiratory droplet transmissibility of clade 2.3.4.4b viruses is variable. Therefore, continued monitoring and risk assessment for emerging HPAI H5N1 viruses is essential to better understand their pandemic potential.

(SNIP)

A limitation of this study is that transmission was assessed in a single mammalian model under defined laboratory conditions, which may not fully capture variability in natural exposures or host species. 

Only single isolates of each genotype were evaluated,and the BC2032-H5N1 virus used here was plaque-purified, capturing only one variant from a clinically heterogeneous sample.

Additionally, female ferrets were used in our  experiments, whereas the CDC study employed male ferrets; potential effects of sex on disease severity or transmission efficiency were not assessed. 

Finally, modest sample sizes could limit detection of rare transmission events.

Overall, these findings underscore that while some clade 2.3.4.4b H5N1 viruses can transmit via respiratory droplets, transmission efficiency is variable and may be dependent on virus genotype, pathogenicity, and other host and/or environmental factors. Therefore, it is critical to continue monitoring and risk assessment for emerging HPAI H5N1 viruses to better understand their pandemic potential. 

 

Obviously, there is still a great deal of uncertainty in influenza research. This isn't the first time we've confronted conflicting data, nor will it be the last.  A few past blogs include:

When Studies Collide (COVID-19 Edition)

When Flu Vaccine Studies Collide

When Studies Collide (Revisited)

Why Preprints Are Only Preprints

A reminder that gaining scientific knowledge is a process . . . one that evolves over time and often involves detours, setbacks, and constant reevaluation. 

Assuming scientific certainty about anything is often the first step towards a humbling. 

But even with its limitations, it is still the best method we have to understand our surroundings.