Emerg. Microbes & Inf.: Novel emerging reassortant H6 avian influenza viruses with internal genes from G57 genotype of H9N2 pose potential zoonotic risk

#19,342

A little over a year ago, in JOI: Prevalence and Transmission of Influenza A (H6) Viruses Pose a Potential Threat to Public Health, we revisited the H6 family of influenza A viruses, which are endemic in Asian poultry and are believed to have some degree of zoonotic potential. 

Long time readers will recall that H6N1 briefly made headlines in 2013 and 2014 after a college student in Taiwan was hospitalized with pneumonia (see Taiwan CDC: Epidemiological Analysis Of Human H6N1 Infection) and several dogs were found infected (see EID Journal: Influenza A(H6N1) In Dogs, Taiwan).

But as an LPAI virus (and neither H5 or H7), it isn't considered a `reportable' disease in poultry or wild birds by WOAH, and therefore our knowledge of its spread and evolution is limited.  

That said, over the past decade we've seen growing interest by Chinese scientists in the spread and evolution of H6, particularly since it reassorts readily with another zoonotic risk: LPAI H9N2.  A sampling of recent blogs include:

J. Inf.: Zoonotic Threat of Novel H6N2 Avian Influenza Virus with Internal Genes Exclusively Derived from H9N2, China, 2025

Preprint: Progressive Adaptation of H6N1 Avian Influenza Virus in Taiwan Enhances Mammalian Infectivity, Pathogenicity and Transmissibility

Study: Influenza A (H6N6) Viruses Isolated from Chickens Replicate in Mice and Human lungs Without Prior Adaptation

H9N2 is a ubiquitous, and highly promiscuous avian influenza virus, which reassorts easily with other influenza A strains and has a record of lending its internal genes to more dangerous HA subtypes (see PNAS: Evolution Of H9N2 And It’s Effect On The Genesis Of H7N9).

Today's study describes 6 H6 reassortants - all carrying the internal genes from H9N2 - and 5 with its NA from H5N1, and 1 from H9N2.  Of note, the H6N2 isolate showed dual receptor binding to both avian and human-like receptor cells. 

The three representative isolates tested (NJ2501, AH25107, and CZ56) produced high virulence in mice, while all 6 produced respiratory symptoms in chickens, and transmitted efficiently among birds.

Due to its length and technical nature, I've only posted some excerpts. Follow the link to read the report in its entirety.  I'll have a postscript after you return.

Novel emerging reassortant H6 avian influenza viruses with internal genes from G57 genotype of H9N2 pose potential zoonotic risk

Zhimin Wana,b,c,d*, Wenjie Jianga,b,c,d*, Xudong Caoa,b,c,d, Xingyao Guoa,b,c,d, Xinyan Hea,b,c,d, Jianjun Zhange,Xinran Chua,b,c,d, Xinyi Jia,b,c,d, Yu Liua,b,c,d, Xuefeng Yina,b,c,d, Zhehong Zhaoa,b,c,d, Jixiang Wanga,b,c,d,Wei Gaoa,b,c,d, Quan Xiea,b,c,d, Tuofan Lia,b,c,d, Hongxia Shaoa,b,c, Aijian Qina,b,c, Yuhai Bif,g,h andJianqiang Yea,b,ca 

In recent decades, multiple novel reassortant avian influenza viruses (AIVs) carrying internal genes derived from H9N2 viruses have emerged in poultry in China and have repeatedly caused human infections, highlighting the pivotal role of the H9N2 internal genes cassette in facilitating cross-species transmission. 

In this study, five H6N1 and one H6N2 AIVs were isolated from chickens and Houdan chickens exhibiting respiratory symptoms. Genetic analyses revealed that the hemagglutinin (HA) genes of these H6 AIVs belonged to the ST339-like lineage and originated from H6 AIVs circulating in domestic geese in China, whereas the neuraminidase (NA) genes were derived from H9N2 or H5N1 AIVs, respectively. 

Notably, all six internal genes of these H6 isolates were derived from the G57 genotype H9N2 virus. In vitro studies demonstrated that these H6 AIVs replicated effectively in both avian and mammalian cells.

The H6N2 isolate displayed dual receptor binding affinity for both avian-like and human-like receptors, whereas the five H6N1 viruses showed no detectable receptor binding affinity under the assay conditions in vitro. Reverse-genetics reassortant assay further revealed that the H6N1 HA itself possesses intrinsic dual receptor binding affinity.

Furthermore, these H6 isolates exhibited high virulence in mice, and induced obvious respiratory symptoms in chickens, with efficient transmission among birds. 

Collectively, our findings demonstrate that H6 AIVs carrying the G57 H9N2 internal gene constellation are actively circulating in chicken populations and pose a substantial threat to poultry health, underscoring their potential risk to public health and the need for continued surveillance at the poultry-human interface.

(SNIP)

Discussion 

The  continuous emergence of the novel reassortant AIVs poses a great threat to both poultry industry and public health. In this study, we identified and characterized six novel reassortant H6N1 and H6N2 AIVs circulating in chickens with respiratory symptoms, all of which harbour internal genes from the G57 genotype H9N2 virus. 

Our findings provide further evidence that H9N2 viruses serve as a critical genetic backbone facilitating the generation of novel reassortant AIVs with enhanced fitness in poultry and increase zoonotic potential.

(SNIP)

In addition to their mammalian pathogenicity, these H6 viruses demonstrated efficient infection and transmission in chickens. Viral shedding was detected in both infected and contact chickens (Figure 8), indicating effective direct-contact transmission of these novel H6 viruses. The ability to spread efficiently within poultry is a critical factor for viral maintenance and amplification, which increases the likelihood of further reassortment and spill-over events. 

Compared with previous reports in which H6 viruses showed limited transmission in poultry [26], the strains described here appear to have acquired enhanced transmissibility, possibly due to their adapted internal genes of H9N2 virus origin.

        (SNIP)

In conclusion, our study highlights the evolution of H6 AIVs through reassortment with G57 genotype H9N2 viruses and demonstrates that such reassortment can result in AIVs with enhanced pathogenicity and cross-species transmission potential. 

These findings underscore the importance of continuous surveillance of AIVs in poultry flocks in China, particularly those carrying H9N2 internal genes, as they may serve as precursors to zoonotic or even pandemic AIVs.

       (Continue . . . )

While most people think first of `H5N1' when they hear about novel flu strains, the CDC's IRAT lists 27 avian, canine, or swine subtypes/variants with pandemic  potential.  

Among the top 10 zoonotic influenza A viruses (ranked by likelihood of emergence) the CDC has placed H5N1 as 7th on the list, while H9N2 comes in at #5.

And despite having caused documented human infections, a number of novel flu subtypes (e.g. H3N8, H5N5, H6N1, and H7N4) have yet to be added to this list. 

The reality is, most of these viruses will never pose a serious public health threat.  But none of them can be ruled out as having pandemic potential.

 Which is why we follow their progress with considerable interest.  

#NPM26: It's a 12 Volt Life

CDC Infographic

Note: This is the 20th day of National Preparedness Month. Follow this year’s campaign on Twitter by searching for the #NatlPrep #BeReady or #PrepMonth hashtags.

This month, as part of NPM26, I’ll be rerunning some updated preparedness essays, along with some new ones.

#19,341

Most disasters boil down to unscheduled camping - for days, or sometimes weeks - in your home, in a community shelter, or possibly even in your own backyard.

Preparedness can not only make that process possible, it can make it far less miserable as well. 

But, as anyone who has ever tried to buy a loaf of bread or a gallon of milk after a hurricane or blizzard warning has been issued already knows, prepping has to be done well before a disaster looms.

And quite frankly, given the rates of inflation and other global uncertainties, it seems likely that whatever you'd pay today for prep items will be higher in the future.  And that assumes they will still be available. 

If you have unlimited funds, and plenty of room, you can prep in style.  But most people are constrained by limited budgets, and other restraints, and so this list is primarily for them. 

Living in hurricane country, my biggest concerns revolve around prolonged power outages, which also can impact other utilities (including water, sewer, and internet). 

• Following last 2024's one-two punch from Hurricanes Helene & Milton, I got my power back after only 4 days (although internet took a week). Before that, I went nearly a week without power following Irma in 2017, but many people had it far worse (most of Puerto Rico was without power for months after hurricane Maria in 2017).

• Not quite five years ago, in February of 2021, 3 successive winter storms swept across Texas, Louisiana, and Oklahoma, causing the worst collapse of the Texas energy grid on record (see Texas: The Latest - But Not The Last - Grid Down Crisis), resulting in hundreds of deaths (see City of Austin & Travis County 2021 WINTER STORM URI AFTER-ACTION REVIEW).

• And just last July, the U.S. Department of Energy published a 73-page report that warns that if current schedules for retirement of reliable power generation (especially baseload) continue, without enough firm replacement, the risk of blackouts in 2030 could increase by 100× over current levels.

While those with tens of thousands of dollars to spend can have a whole-house solar system or generator - one capable of running freezers, refrigerators, and air conditioners - even a small budget system can make life without grid power a little more bearable.

My minimum goal is to have enough sustainable power for lights, radio, phone charging, a personal MP3 player, and fans. Trying to run appliances, HVAC, or other high-draw devices is simply beyond my budget (but if you have enough money . . . . it can be done ).

The following is an example of how one can put together a basic plug-and-play mini solar power system for around $100; one that will keep phones, lanterns, and some mini-fans charged and running for days.

While I'm not recommending specific brands or suppliers, these photos are all typical of items I've purchased and used myself. 

This is my `bug out' solar kit; What I would grab if I had to abandon my home - and the bulk of my preps - in a hurry (note: I have 2 rechargeable USB batteries and an MP3 player). It all fits in a tiny duffle bag that weighs less than 5lbs. 

For a bit more money you could go for a slightly bigger solar panel, additional USB battery banks, and maybe a personal MP3 player, walkie-talkies, and an emergency radio.  As the following photo illustrates, this type of modular system can be expanded over time.

The biggest downside to these types of setups is you are limited to USB (typically 5 volt) appliances. Fine for flashlights, phones, and MP3 players, but not nearly as versatile as a 12 volt system. 

For 12v/110v power, you could opt to buy a Jackery, Bluetti, EcoFlow, or similar `Solar Battery' setup, but it would set you back $400 -$1000+ (plus solar panel). And if it breaks, you don't have many options beyond sending it back for repair.

However, if you build your own - and keep a few spare parts on hand - you should be able to to keep it running yourself. (note: If you aren't comfortable working with these types of components, get help from someone who is). 

In 2024 I described building a rudimentary LiFePo4 power station (see picture below), which packed a decent 600 Watt/hour capacity. LiFePo4 batteries are lighter than lead/acid, are far less dangerous, and can be charged and discharged (fully) thousands of times.

My system featured dual 12V Car Cigarette Lighter Sockets (for CPAP, Electric cooler/fridge, or Inverter), 2 USB outlets, and I added a small 110v inverter. It is recharged by a 100 watt solar panel (shown on left). 

After my last hurricane I endeavored to improve my 12-volt battery bank (for build details, see Post-Milton Improvements To My Power Preps)

Weighing in at less than 15 lbs, this 50 amp/hr (600 watt/hour) setup is self contained, with storage for cables, a wall charger, and a small 110v inverter. All you need to add is a solar panel (100 watt or better).

The plastic carrying case was $12 at Harbor Freight, the 50 amp/hr battery was $109 on Amazon, and the rest of the build (solar charge controller, cables, lighted output panel, inverter) added about $60. 

All in, including taxes, this can be assembled in a couple of hours for less than $200.  I built a second, lighter weight and smaller version using a 20 amp/hr LiFePo4 battery (240 watt/hours) for less than $140. Something to keep on the bedside table.

Whether home built, or store bought, these `solar generators' can greatly expand what you can do during a prolonged blackout. They can recharge any USB item, run most 12 volt appliances, and some can power small 110 volt appliances for a short period of time. 

Even without the 110 volt output, which on small systems provides limited value, these setups can power a lot of useful items. 

Two years ago I purchased some very nice 4-packs of LED lanterns, and some USB battery powered water pumps that attach as a faucet to large water jugs. Just three days after they arrived I endured a 3-day water outage at home, and found the faucets actually worked pretty well.

Every home should have a battery operated radio (with NWS weather band), yet many do not. Some are available with crank or solar charging, but most have rechargeable batteries via a USB port.  



A 12 volt system (of sufficient size) can power a mini-fridge, or electric cooler,  and can not only keep food from spoiling, and drinks cold, it can keep medications like insulin cool.   

As for entertainment - which should not be discounted during a prolonged power outage - while a USB setup will power and charge a personal MP3 player, a 12 volt system can run a DVD player. 

As an aside - I've collected (public domain) OTR (Old Time Radio) shows since the early 1990s, and have literally thousands of hours stored on CDs in MP3 format. The Internet Archive has a huge repository where you can download them for free, along with thousands of audiobooks.

I keep a couple of MP3 players filled with these shows and with audiobooks in my bug-out bag. When the power and internet were down, they have provided me with hours of entertainment.

Over the years I've bought several cheap MP3 players ($20-$30) and filled them with thousands of hours of these shows (mostly from the 1940s and 1950s), giving them as gifts. And the nice thing is, you don't have to wait for an emergency to enjoy them.

Admittedly, since I lived happily for nearly 15 years aboard boats (2 sailboats, 1 power boat) here in Florida - where 12 volts ran just about everything - I may be a bit more amenable to the 12 volt life than others.  

But despite its obvious limitations, it sure beats cursing the darkness.  

EID Journal: Detection of HPAI A(H5N1) Virus in Cat and Rats during Outbreak in Backyard Poultry, United States, 2025

 

#19,340

Today we've a dispatch, published yesterday in the CDC's EID Journal, which describes the findings of HPAI H5N1 in a cat and a rat from an Illinois farm which experienced a bird flu outbreak in March of 2025.  

While it is not exactly `news' that both species are susceptible to H5N1 infection (see below), our understanding of how HPAI may spread among peridomestic animals on farms remains limited. 

EID Journal Dispatch: Seroprevalence of Influenza A(H5N1) Virus in Domestic Cats at Epicenter of Dairy Cattle Outbreaks, California, USA, 2024–2026

MMWR: Serologic Evidence of HPAI A(H5N1) Virus Infection in a Veterinary Professional Exposed to an Infected Domestic Cat

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

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

CDC MMWR: HPAI H5N1 Virus Infection of Indoor Domestic Cats Within Dairy Industry Worker Households — Michigan, May 2024

The USDA's Detections of Highly Pathogenic Avian Influenza in Mammals dashboard lists more than 200 feline detections in the U.S. and a dozen H5N1 positive rats. Curiously, while I can find one entry of a cat from Bond County Illinois in March of 2025 (which may, or may not, refer to the cat in this study), there appear to be no reports of any rats infected in Illinois. 

According to this report, a farmer brought the remains of six animals (a chicken, a turkey, a goose, 2 Guinea fowl, and a rat (Rattus norvegicus)) to his veterinarian after nearly all of his chickens died. Suspecting H5N1, the vet sent the remains to the University of Missouri Veterinary Medical Diagnostic Laboratory (VMDL; Columbia, MO, USA) for postmortem examination.

VMDL ran a qRT-PCR on 1 chicken sample, which came back presumptive  positive for H5, and forwarded tissue samples to NVSL in Ames, IA for confirmatory testing (which verified HPAIV H5N1 clade 2.3.4.4b virus).

Four days after the first report, the local vet visited the farm and collected the remains of a 13-year-old cat and a second feral rat from the farm. They were then sent to the University of Illinois Veterinary Diagnostic Laboratory (VDL) for necropsy and additional testing. 

According to this report, state and local authorities were notified, and the Illinois Department of Agriculture and USDA quarantined the farm and monitored it for 4 months.

Today's report is primarily an analysis of the extensive infection of both the cat and the rat submitted to VDL. Sadly, while the first rat underwent necropsy, it was never tested for H5N1, so all we have is a sample of one.  

This seems like it was a great opportunity to explore the potential spread of HPAI among peridomestic animals on an infected poultry farm. But there is no indication that any attempts were made to collect and test additional samples. 

That said, this is a fascinating report that strongly suggests that an H5N1 farm outbreak should be viewed as a whole-premises event. Animals living around infected livestock - including cats and rats - may also be infected, and contribute to the evolution and further spread of the virus. 

Another finding of this dispatch is that all 3 animal species tested (cat, rat, and chicken) carried the PB2 E627K mutation which is generally considered a mammalian adaptation.  While not unheard of, reports of this mutation in birds are rare. 

Since only 1 chicken was tested, we've no idea of the frequency of this mutation in the rest of the flock.  

I've only posted the Abstract and some excerpts from the dispatch, so follow the link to read it in its entirety.  I'll have a postscript after the break.

Detection of Highly Pathogenic Avian Influenza A(H5N1) Virus in Cat and Rats during Outbreak in Backyard Poultry, United States, 2025

Suzanna M. Storms, Jade Rathmann, Lynette Hemker, Miranda Vieson, and Leyi Wang

Abstract

In 2025, highly pathogenic avian influenza A(H5N1) virus was detected in a poultry flock in Illinois, USA. Quantitative reverse transcription PCR, sequencing, and histopathology on cat and rat samples from the farm showed multiple positive tissues and high sequence identity to an avian isolate. Small mammals might contribute to H5N1 transmission.

The Study

On March 12, 2025, a farmer in southern Illinois with a small backyard poultry flock brought remains of 6 animals to their primary veterinarian for a necropsy workup after acute illness and near-complete mortality (100/105 birds) of the flock. The farm, ≈2 miles from a 25,000-acre reservoir lake within the Mississippi Flyway, housed 4 turkeys (Meleagris gallopavo), 1 goose (Anser sp.), 20 Guinea fowl (Numida spp.), 80 chickens (Gallus gallus domesticus), 17 cattle, 15 cats, and 2 dogs. Because HPAI virus (HPAIV) was suspected, the 6 animals, a chicken, a turkey, a goose, 2 Guinea fowl, and a rat (Rattus norvegicus), were sent to the University of Missouri Veterinary Medical Diagnostic Laboratory (VMDL; Columbia, MO, USA) for postmortem examination.

VMDL collected and evaluated fresh and formalin-fixed tissues and performed influenza A virus (IAV) quantitative reverse transcription PCR (qRT-PCR) on 1 chicken sample, according to guidelines from the US Department of Agriculture (USDA) National Animal Health Laboratory Network (NAHLN; https://www.aphis.usda.gov/labs/nahln). The sample tested presumptive positive per NAHLN guidelines, and VDML subtyped it as H5 influenza. VDML then forwarded the sample to the National Veterinary Services Laboratories (NVSL; Ames, IA, USA) for confirmatory testing, which verified HPAIV H5N1 clade 2.3.4.4b virus.

Further PCR testing of the avian species for Mycoplasma gallisepticum, M. synoviae, and avian paramyxovirus were all negative. The necropsy findings reported hepatitis, pulmonary hemorrhage, and pulmonary edema in the poultry species and bronchopneumonia and meningoencephalitis in the rat. No additional testing was performed on the rat or other bird species.

Upon report of HPAIV on the farm, state and federal agencies were notified. The Illinois Department of Agriculture and USDA quarantined the farm and monitored it for 4 months.

On March 16, 2025, the primary veterinarian collected the remains of a 13-year-old domestic shorthaired cat and a second feral rat from the farm. In conjunction with Illinois Department of Agriculture and USDA, the cat and rat specimens were sent to the University of Illinois Veterinary Diagnostic Laboratory (VDL; Urbana, IL, USA) on March 19. VDL performed gross necropsy and collected fresh and formalin-fixed tissues. VDL screened lung tissues from the cat and rat for IAV by qRT-PCR, following NAHLN guidelines. The cat lung tested presumptive positive (cycle threshold [Ct] value 21.2), subtyped as H5; NVSL confirmed H5N1 clade 2.3.4.4b virus. The rat lung tissue was negative upon initial screening, but NVSL conducted follow-up testing on tracheal swab samples, which were H5N1-positive.

Quantitative reverse transcription PCR results from HPAIV A(H5N1) in cat and rats during outbreak in backyard poultry, United States, 2025. Specimens obtained from a cat (A) and a rat (B) found dead on farm where the outbreak occurred were confirmed to be positive for H5N1 clade 2.3.4.4b, genotype D1.1 virus.

(SNIP)

Conclusions

We describe a strain of H5N1 that resulted in high mortality in a poultry flock and fatal illness in small mammals on a backyard farm in Illinois, USA. Our results show that extensive systemic H5N1 virus spread occurred in both cat and rat tissues after natural infection. Rat nasal turbinates and trachea preferentially expressed α2,3-linked sialic acid receptors relative to lung, likely explaining the lower Ct values in upper respiratory tissues and presence of bacterial bronchopneumonia, potentially leading to increased viral shedding (10).

Cat feces and urine have previously been shown to harbor H5N1 virus (11,12), which our results corroborate. Rats have previously been reported to harbor HPAIV in agricultural settings and have been detected in the current epizootic (13,14). Detection of HPAIV in rat urine and kidney tissue suggests that rodent urine could be a potential transmission medium and warrants further investigation.

Rats reside on many farms, can predate birds, and might serve as an intermediate step between infected avian species and susceptible mammalian hosts (15). That coexistence is particularly threatening for commercial poultry and swine confinement farms, which frequently harbor rodent populations despite strict biosecurity efforts. A limitation of our study was that no virus isolation was performed on tissues or urine due to biosafety constraints.

Although cats have been shown to participate in HPAIV transmission, our findings indicate that further investigation is needed to clarify the role of rodents. This study raises awareness of small mammals at the wildlife–livestock interface and highlights the potential role of rats in influenza transmission to commercial livestock production.

Dr. Storms is a veterinarian-scientist at Texas A&M Veterinary Medical Diagnostic Laboratory, College Station, Texas, USA. Her research interests center around influenza virus transmission and diagnostic development.

Our continued reliance on passive surveillance severely limits our ability to understand the ecology and threat of HPAI H5. 

Because of the limited sampling on this farm, we can't say whether the PB2-E627K mutation was `fixed' in the poultry flock, or whether rat-to-rat transmission occurred, or whether any other species in and around the farm were affected. 

And we saw last year, in Nature: Lengthy Delays in H5N1 Genome Submissions to GISAID, the median delay in submitting sequences to GISAID was 7 months (228 days), with some countries taking nearly 2 years. 

Despite the mounting evidence of the susceptibility of cattle, sheep, goats, pigs, cats, and rats (ad nauseam) to HPAI H5 - and the continued calls from the scientific community for more aggressive surveillance and testing of livestock (see here, here, here, here, and here) - the world seems content to don blinders and hope for the best.

Sadly, the world continues to treat the spread of HPAI as more of an economic or political concern, than a public health threat. And while that optimistic assessment may be true today, there are no guarantees for tomorrow.

Preprint: Near real-time data on the human neutralizing antibody landscape to influenza virus in summer of 2026 shows antigenic advance of H3N2 subclade K region D mutants and H1N1 D.3.1.1 Sa mutants

 

#19,339

Hopefully the daunting title of today's paper won't deter both of my readers, because the preprint in question is well worth reading given what we are already seeing with the approach of the Northern Hemisphere's flu season:

Taiwan CDC: Both influenza and the COVID-19 epidemic are currently in their peak season, with influenza cases continuing to rise

South Korean CDC Issues Early Seasonal Flu Epidemic Advisory

Japan MHLW Reports Unusually Early Start to the Fall Flu Season

Due to the time it takes to manufacture and deploy hundreds of millions of doses, recommendations on the composition of the northern hemisphere’s vaccine must be made in February of each year, while recommendations on the southern hemisphere’s vaccine are made in late September.

Flu viruses, however, don't stop evolving.  Last year, we famously saw the late emergence of a `drifted' H3N2 subclade K virus (see Increasing Concerns Over A `Drifted' H3N2 Virus This Flu Season), which was less than an ideal match to the vaccine. 

H3N2, in particular, has a reputation for rapid evolution (see The Enigmatic, Problematic H3N2 Influenza Virus), and threw us curve balls in 2014 and again in 2017.  Since 2009, H1N1 has been viewed as the more stable subtype, but it too continues to evolve. 

Last February, following observed antigenic changes in all three circulating strains (H1N1, H3N2, Influenza B), the WHO recommended changes to all 3 components of the fall vaccine, which is being delivered now.  Later this month, they will meet to discuss next year's Southern Hemisphere flu vaccine. 

But, as the title of today’s preprint suggests, both H3N2 and H1N1 have continued  to evolve, and recent data suggest that some newly emerged variants are less well  neutralized by human sera - including sera from a vaccinated subset.

None of this suggests we face an imminent `vaccine failure'. Despite last year's mismatch with H3N2 Subclade K, the flu vaccine still produced a beneficial VE (Vaccine Effectiveness) according to the MMWR. 

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.

But it does suggest VEs this year could be lower than desired, regardless of whether H1N1 or H3N2 dominates this winter. Additionally, the future course and speed of these antigenic changes are unclear, which complicates decisions on next year's Southern Hemisphere vaccine. 

Among their findings, the authors identified 72 serum samples in which an H1N1 D.3.1.1 virus carrying G155E was more than twofold less effectively neutralized than a comparable virus without that mutation. Those samples tended to come from teenagers and young adults (roughly 15–25 years old).

 

It is well recognized that one's first flu exposure makes a significant, and lasting, impression on the immune system (see Nature: Declan Butler On How Your First Bout Of Flu Leaves A Lasting Impression). People in this age cohort were first exposed to H1N1 either during or after the 2009 pandemic, whereas older adults were likely first exposed to the previous H1N1 virus. 

There is a lot here to unpack, and there are still a lot of questions of how these emerging variants will impact this year's flu season (or beyond). 

Those wishing a deeper dive will want to follow the link to read the full 18-page preprint, but fair warning, much of it is highly technical.  I'll have a bit more after the break.

Near real-time data on the human neutralizing antibody landscape to influenza virus in summer of 2026 shows antigenic advance of H3N2 subclade K region D mutants and H1N1 D.3.1.1 Sa mutants
 Caroline Kikawa, Andrew Butler,  John Huddleston, Sam A Turner, Heidi Peck,  Janet A Englund, Kirsten Lacombe  Michael Busch, Marion C Lanteri, Mars Stone, Bryan Spencer,  Alexander L Greninger, Derek J Smith, Stephanie Wallace, Helen S Marshall,  Shidan Tosif, Scott E Hensley,  Ian G Barr,  Jesse D Bloom
doi: https://doi.org/10.64898/2026.09.15.751855
This article is a preprint and has not been certified by peer review [what does this mean?].

Preview PDF

Abstract

Human seasonal influenza evolves rapidly, necessitating twice yearly decisions about whether to update the strains in the vaccine. To help inform this decision, we have been using high-throughput sequencing-based neutralization assays to make twice yearly measurements of how recent human sera neutralize current human H3N2 and H1N1 strains.

Here we provide the third installment in this series of measurements by reporting 47,851 titers representing neutralization of 148 viral strains by 325 human sera collected between April and August of 2026.

Our measurements show that new H3N2 subclade K strains with mutations in antigenic region D and new H1N1 subclade D.3.1.1 strains with mutations in antigenic region Sa (such as G155E) have reduced neutralization by human sera, with notable heterogeneity in the impact of some of these mutations across sera from different individuals. This paper is accompanied by an interactive summary (https://jbloomlab.github.io/flu-seqneut-2026/summary.html) that enables detailed exploration of the results, and all titer data are publicly available for further analysis to aid vaccine antigen selection and studies of viral evolution.

(SNIP)

Discussion

We have measured how a large set of human sera neutralize current human H3N2 and H1N1 influenza strains. Our results show that the two subclades that spread widely over the last year (subclade K for H3N2 and D.3.1.1 for H1N1) are now spawning descendants with reduced neutralization by human sera.

These descendant strains have HA mutations that are associated with decreased neutralization, some of which have arisen independently in different combinations.

• For H3N2, mutations at sites in antigenic region D (e.g., 223 and 222) have arisen recurrently and reduce neutralization; mutations at sites in antigenic regions A and B are also present in strains with reduced neutralization (e.g., 145, 156, 157). 

• For H1N1, strains with mutations at sites in antigenic region Sa (e.g., 155 and 157) have arisen recurrently and reduce neutralization; mutations at sites in antigenic regions Sb and Ca1 (e.g., 190 and 205) are also present in strains with reduced neutralization.

However, the diversity of new antigenic variant strains makes it challenging to use our data alone to determine which strains will dominate a year from now. For H1N1, our data show that D.3.1.1 is antigenically advanced over D.3.1, and virtually all human H1N1 influenza observed over the last few months is D.3.1.1 or a descendant strain.

However, it is uncertain which more antigenically advanced variant of H1N1 will spread over the next year— G155E reduces neutralization of all H1N1 strains and has recently arisen recurrently, but it occurs in multiple genetic backgrounds and there are also other antigenic mutations that could outcompete it. Similarly, although our data identify multiple new antigenic variant strains of subclade K, it remains unclear which of these new variants will dominate over the next year.

(Continue . . . )

In addition to these antigenic changes, we are also following concurrent reports of creeping antiviral resistance in H1N1 (see Eurosurveillance: Emergence and spread of NA-I223V and NA-S247N double-mutant A(H1N1)pdm09 influenza viruses with reduced oseltamivir susceptibility in the Netherlands and beyond, 2023 to 2026). 

While neither of these trends are anywhere near a crisis point, they are reminders that the global `fluscape' is constantly changing, and that every flu season remains highly unpredictable. 

Reduced VE or not, this year's vaccine is still expected to provide modest - perhaps even substantial - benefit.  So I'll still gladly roll up my sleeve this fall, albeit with slightly tempered expectations.    

I'll avail myself of antivirals if I am infected.  But I'll also be wearing a facemask in crowded indoor venues, using copious amounts of hand sanitizer, and avoiding crowds whenever possible. 

Because prevention is always preferable to a treatment.

EID Journal: Experimental Highly Pathogenic Avian Influenza A(H5N1) Clade 2.3.4.4b Virus Infection in Alpacas, 2026

 

#19,338

In 2024 - just over 2 months after the discovery of HPAI H5N1 in U.S. dairy cattle - the USDA reported that HPAI H5N1 had been Detected In Alpacas from a premises (in Idaho) where HPAI-affected poultry had recently been depopulated. 

Alpacas belong the the family Camelidae, which includes 3 types of camels ( dromedary camels, Bactrian camels, wild Bactrian camels), and 4 lamoids (llama, alpaca, guanaco, and vicuña).

Camelidae - including both camels and alpacas - are known to be susceptible to MERS-CoV (see EID Journal: MERS-CoV Antibodies In Alpacas - Qatar), but less is known about their susceptibility to influenza A viruses.  

In recent years we've seen the mammalian host range of HPAI continue to expand,  with the virus detected in horses, pigs, goats, sheep, mink, dogs, and cats and a growing list of peridomestic animals (see below).

Some animals are clearly more susceptible than others to the virus, and some appear to be dead-end hosts; susceptible to infection but unlikely to contribute to the spread of of the virus. 

In an attempt to determine how vulnerable Alpaca are to the virus, and their ability to carry, and shed the virus, researchers at Germany's FLI (Friedrich-Loeffler-Institut) experimentally infected 6 alpaca with the HPAI H5N1 genotype B3.13 (`bovine') virus.

While they found that H5N1 B3.13 can induce a mild, but productive, upper respiratory infection in alpacas (including nasal shedding of the virus for several days and seroconversion), it still isn't established whether alpacas can efficiently transmit virus to one another. 

That said, there would seem to be enough here to warrant inclusion of camelids in farm biosecurity and surveillance plans. 

Due to its length, I've only posted the highlights. Follow the link to read the report in its entirety. 

Research
Experimental Highly Pathogenic Avian Influenza A(H5N1) Clade 2.3.4.4b Virus Infection in Alpacas, 2026
 
Jacob Schön , Angele Breithaupt, Nico Joel Halwe, Maxi Hertel, Ann Kathrin Ahrens, Andrea Aebischer, Donata Hoffmann, and Martin Beer
 
Abstract

Highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b virus continues to spread globally and sporadically transmits from avian reservoirs to mammalian hosts. In May 2024, H5N1 infections in young goats and alpacas in the United States were reported. Nevertheless, the overall susceptibility of camelids to clade 2.3.4.4b virus remains unclear. 

We conducted a controlled experimental infection study in 6 alpacas, assessing clinical signs, viral shedding, tissue distribution, and serologic responses after intranasal inoculation with HPAI H5N1 genotype B3.13 virus. 

Observed illness was generally mild; body temperature increased slightly and food intake reduced for up to 3 days postinfection. We detected viral RNA in nasal swab samples and confirmed infectious HPAI H5N1 virus. Immunohistochemistry and RNA in situ hybridization detected virus only in the nasopharyngeal tonsil and nasal conchae at 4 days postinfection.

Our findings suggest alpacas are susceptible to productive H5N1 infection, highlighting implications for livestock surveillance and biosecurity in regions with ongoing circulation.

       (SNIP)

We experimentally confirmed that alpacas can be intranasally infected with a bovine HPAIV H5N1 B3.13 isolate, leading to subsequent nasal shedding of infectious virus. IHC and ISH confirmed H5N1 virus replication in the nasopharyngeal tonsil and the nasal conchae. Productive infection was corroborated by seroconversion at 20 dpi. We detected individual variation of neutralizing antibody levels, but the small number of animals does not enable general conclusions. The infection did not cause fever, but alpacas reduced feed intake. Whether the viral load shed by the alpacas would be sufficient to cause transmission to contact animals remains undetermined. Intermittent viral RNA detection and low viral titer at 3 dpi might reflect technical variability of the sampling procedure rather than reduced shedding.

Our data did not suggest that alpacas replicate H5N1 clade 2.3.4.4b genotype B3.13 virus with exceptionally high efficiency. However, nasal replication occurred, and infectious virus was detectable in nasal swab samples for up to 6 dpi, but sequencing did not indicate accumulation of mutation to that timepoint. Nevertheless, viral adaptation after infection or shedding to naive contact animals or humans cannot be excluded. A follow-up study should include direct-contact animals to assess the biologic relevance of low-level shedding and to clarify the potential role of alpacas in H5N1 transmission. In addition, future studies should include experimental intramammary inoculation of female alpacas to evaluate susceptibility via that route.

In conclusion, H5N1 clade 2.3.4.4b virus will likely continue to drive substantial mortality rates in wild birds and marine mammals across North and South America. Risk for virus spillover into domestic animals, including poultry and potentially camelids, will continue considering their large populations on the continents. The demonstrated capacity of H5N1 clade 2.3.4.4b virus to acquire mammalian-adaptive mutations heightens concern about cross-species transmission and possible establishment in new mammalian hosts, which could intensify wildlife losses, disrupt livestock production, and generate new zoonotic risks. Sustained surveillance, strengthened biosecurity, and rapid response measures will be essential to limit those impacts.

       (Continue . . . )

 

WHO: Bangladesh Reports 4th H5N1 Human Infection for 2026

 


#19,337

In their latest Influenza at the human-animal interface Summary and risk assessment (8 August to 6 September 2026) - published this week - the WHO has announced the 4th H5N1 case in a Bangladeshi child in the past 9 months.

• Last April, we saw a fatal case reported from the Chattogram Division, in a child who fell ill on January 22nd, was hospitalized on January 28th, and who died on February 1st. The H5N1 infection was only determined posthumously, via lab analysis on Feb 7th.

• In early June we learned of a 2nd case, a child from Sylhet Division who was hospitalized on March 28th with a clinical diagnosis of measles with bronchopneumonia. The child was discharged on March 31st, but delayed testing by the IEDCR only revealed a positive H5N1 result on April 20th.

• And last July the WHO reported a 3rd child - also from Sylhet Division - diagnosed with H5 (later confirmed as H5N1). The child (now recovered) fell ill in May, and reportedly had no travel history and no history of exposure to poultry.

In addition to the new H5N1 case in Bangladesh, the WHO also details 3 H9N2 cases in China (previously reported in this blog) and 2 H1N2v Cases from Michigan (reported by CDC here).

Avian influenza viruses in humans

A(H5N1), Bangladesh

On 30 August, Bangladesh, through the national IHR focal point, notified WHO of one laboratory-confirmed human infection with an A(H5) virus in a child from Rangpur division. On 15 August 2026,  the child developed a fever, cough and rhinitis and was admitted to hospital on 17 August. 

On 18 August, a nasopharyngeal swab and throat swab was collected as part of hospital-based influenza surveillance and tested positive for influenza A(H5) by real-time RT-PCR at the icddr,b laboratory on the same day. The sample was subsequently confirmed positive for influenza A(H5N1) at the Molecular and Genomic Laboratory Department of Institute of Epidemiology, Disease Control and Research (IEDCR) and National Influenza Centre (NIC) of Bangladesh. Genetic sequencing is underway. The child remained hospitalized and was improving clinically at the time of reporting.

There was no reported history of travel outside the area of residence. The child had a history of exposure to duck and chickens, including some that were sick, in the household and adjacent households. Poultry meat and oropharyngeal swab specimens collected from several backyard chickens on 26 August tested negative for influenza A(H5).

Close contacts were identified and placed under monitoring and all contacts remained asymptomatic during the observation period, except for two health care workers. Respiratory specimens collected from these two individuals tested negative for influenza A viruses.

This is the 4th laboratory-confirmed human case of avian influenza A(H5) reported in Bangladesh in 2026.

While full genetic sequencing has not been released, the H5N1 virus circulating in India and Bangladesh is typically clade 2.3.2.1a - not 2.3.4.4b which is currently dominant in much of Europe, Asia, and North/South America.

This is the 16th case reported by Bangladesh since 2008 (2 fatal: 1 in 2013 and 1 in 2026), and it reminds us that older clades of the H5 virus continue to circulate, and occasionally spill over into humans. 

While this is just the 10th human H5 case reported to WHO in 2026 (see chart below), the expectation is that many cases go unreported around the globe.