Preprint: Hematogenous Neuroinvasion and Genotype-dependent Transmission of Influenza A H5N1 Viruses in the Cat Host

 

Based on USDA Data

#19,063

Based on limited - and admittedly opportunistic - surveillance, felines (domestic cats, mountain lions, bobcat, etc.) are (excluding dairy cattle) the non-human mammalian species which are most often reported to be infected with HPAI H5N1.

How many fox, skunk, or mice that are actually infected in the wild is unknown. But cats have a known history of susceptibility to the virus (see 2023's A Brief History Of Avian Influenza In Cats).

Over the years we've seen plenty of evidence of Differences In Virulence Between Closely Related H5N1 Strains, with stark differences in mortality rates reported by countries around the world (see chart below).

While there are scores of H5N1 genotypes currently in circulation (and different subclades in India and Cambodia), among clade 2.3.4.4b viruses, two genotypes currently stand out in North America; `Bovine' B3.13 and avian D1.1.

Both have been reported in poultry, dairy cattle, and humans, but the B3.13 appears to be more at home in dairy cattle, while D1.1 is particularly prevalent in wild birds and poultry. 

B3.13 appears to be milder in humans than D1.1, although that is based on a relatively small sample. Neither genotype approach the virulence, however, of many older H5N1 strains or the current clade 2.3.2.1e in Cambodia.

But H5Nx viruses continues to evolve, and the threats we may face tomorrow may be far different.

Today we've a preprint from researchers at Cornell University in NY state, which looks at the course of infection, virulence, and transmissibility of SPF (specific pathogen-free) lab cats when infected with B3.13 and D1.1 genotypes of  H5N1. 

Notably, while we've seen prior evidence suggesting that genotype D1.1 is more problematic in humans (see J.I.D.: Avian influenza virus A(H5N1) genotype D1.1 is better adapted to human nasal and airway organoids than genotype B3.13), this report finds the opposite seems to be true in cats. 

B3.13 infection produced faster disease progression, greater shedding, higher mortality, and efficient (75%) direct contact transmission. Whereas D1.1 infected cats saw slower progression, lower mortality, and no evidence of direct contact transmission. 

Of note: only two isolates were tested; B3.13 from bovine (TX224) with PB2 M631L mammalian adaptation, and D1.1 from a strictly avian source (NY314925).

Given the diversity of viruses within each genotype, there are limits to how much we can assume based on this study.  A D1.1 virus isolated from a mammalian source might well have performed differently. 

Nevertheless, this is a fascinating, and highly detailed, look at the pathogenesis of two frontrunning H5N1 genotypes in cats, which suggests that B3.13 is better adapted to the feline host. 

Due to its length, and complexity, I've only posted the abstract and a brief excerpt from the preprint. Follow the link to read it in its entirety. 

Hematogenous neuroinvasion and genotype-dependent transmission of influenza A H5N1 viruses in the cat host

Salman L. Butt, Ruchi Rani, Mohammed Nooruzzaman, Elena A. Demeter, Pablo S.B. de Oliveira, Gavin R. Hitchener, Diego G. Diel
doi: https://doi.org/10.64898/2026.02.21.707182
This article is a preprint and has not been certified by peer review 

Preview PDF

Abstract

The spillover of highly pathogenic avian influenza (HPAI) A H5N1 virus to mammalian hosts raises major concerns due to its pandemic potential. Cats are frequently affected mammals, often succumbing to systemic and neurological disease. 

Here, we characterized the pathogenesis and transmissibility of two H5N1 genotypes, B3.13 and D1.1, in cats. Infected cats exhibited high-level viremia and virus shedding in nasal, oral, and fecal secretions were consistently detected.

The virus replicated initially in the upper respiratory tract and lungs, followed by systemic dissemination and neuroinvasion. Notably, the virus crossed the blood-brain-barrier by infecting endothelial cells, spreading to astrocytes and neurons, causing multifocal encephalitis.

D1.1-virus infection caused protracted disease with lower shedding and no transmissibility, whereas B3.13 virus caused rapid onset with efficient shedding and transmission. 

These findings reveal critical H5N1 neuropathogenesis mechanisms and highlight mammalian transmission potential in a species with close human contact.

(SNIP)

The primary concern regarding the rapid genetic diversification observed in H5N viruses is the potential emergence of variants with enhanced transmissibility or pathogenicity. Epidemiological evidence indicates that both H5N1 genotypes B3.13 and D1.1 exhibit improved fitness when compared to their ancestral strains.

The B3.13 genotype successfully spilled over into dairy cattle, establishing efficient transmission chains within this novel host species and subsequently spreading to other mammalian- (including humans and cats) and avian hosts.

Similarly, the D1.1 genotype emerged in wild birds, causing the largest infection wave since the introduction of H5N1 in North America. This genotype also crossed the species barrier, jumping from wild birds to dairy cows in three independent spillover events across Nevada, Arizona, and Wisconsin.

       (SNIP)

Collectively, our results suggest that differences in the polymerase activities between B3.13 (TX2/24) and D1.1 (NY3149/25) viruses may contribute to their distinct abilities to  replicate and transmit in the cat host. 

Further investigations are needed to determine whether both viruses replicate to similar levels in avian hosts in vivo. Our study revealed critical aspects of H5N1 virus pathogenesis in a naturally susceptible animal species, emphasizing the risk posed by B3.13 viruses currently circulating in dairy cattle in the U.S. and frequently transmitted to cats. 

       (Continue . . . )

Nature Comms: Baloxavir outperforms oseltamivir, favipiravir, and amantadine in treating lethal influenza A(H5N1) HA clade 2.3.4.4b infection in mice

 

CDC Influenza Antiviral Medications: Summary for Clinicians - Jan 2026

#19,062

During any novel influenza pandemic - even one as long anticipated as H5N1 - it is expected that it will take 6 months or longer before any substantial quantity of vaccine would be available to the general public (see Maggie Fox's SCI AM - A Bird Flu Vaccine Might Come Too Late to Save Us from H5N1).

During that time - as with COVID - we will have to rely heavily on NPIs (Non-Pharmaceutical Interventions) like face masks, hand-washing, and social distancing.

Unlike with COVID, there is hope that one of the currently available influenza antivirals (i.e. oseltamivir, baloxavir, favipiravir, or amantadine) might provide significant treatment benefits. 

Of these 4 options, oseltamivir (Tamiflu) is the only one stockpiled in any quantity.

• Amantadine is no longer used, after it lost effectiveness in 2005
• Favipiravir is primarily used in Japan, and is not FDA approved (although it could be an option under an EUA).
• Baloxavir is in chronic short supply, and is many times more expensive than oseltamivir. 

While none of these drugs are a panacea against influenza infection, all (except amantadine) are expected to reduce the severity and duration of infection; assuming they can be delivered to the patient in the first 24-48 hrs of infection.   

Logistical problems of supply and delivery aside, not all antivirals are comparable in therapeutic impact. Each is subject to different resistance mutations, and some may work better against specific flu subtypes than others. 

While the U.S. government doesn't release exact numbers, oseltamivir makes up well over 90% of all (SNS) stockpiled influenza antivirals, and is the CDC's first drug of choice for treatment of influenza A.

We have seen concerns raised over the effectiveness of oseltamivir against H5N1, including last March in St. Jude Researchers: Current Antivirals Likely Less Effective Against Severe Infection Caused by Bird Flu in Cows’ Milk; excerpt below:

Our evidence suggests that it is likely going to be hard to treat people severely infected with this bovine H5N1 bird flu strain,” said corresponding author Richard Webby, PhD, St. Jude Department of Host-Microbe Interactions. “Instead, reducing infection risk by not drinking raw milk and reducing dairy farm workers’ exposures, for example, may be the most effective interventions.”

“In general, baloxavir [Xofluza] caused a greater reduction in viral levels than oseltamivir [Tamiflu], but neither was always effective,” said first author Jeremy Jones, PhD, St. Jude Department of Host-Microbe Interactions.

There is also the matter of NAI antiviral resistance - which is relatively low right now - but appears to be increasing in both seasonal and novel flu strains (see Emerg. Microbes & Inf: Oseltamivir Resistant H5N1 (Genotype D1.1) found On 8 Canadian Poultry Farms).

Since randomized antiviral trials on humans are highly problematic, nearly all evidence of efficacy against H5N1 come from either observational studies and case reports, or from animal studies.

Last month, in Nature Comms: Oseltamivir and Baloxavir Monotherapy and Combination Therapy Efficacy Against Clade 2.3.4.4b A(H5N1) Influenza Virus Infection in Ferrets, we saw a CDC study which looked at both mono and combination therapy with oseltamivir and baloxavir in ferrets infected with H5N1 (genotype D1.1).

In short, they found:

• Ferrets infected with H5N1 D1.1 and treated with oseltamivir saw little or no clinical or virologic benefit compared to no treatment, with persistent high fevers, weight loss, and systemic viral replication.
• Ferrets treated with Baloxavir saw significantly less fever, weight loss, and viral replication. Some ferrets, however, saw a late rise in fever (after 4 days) and viral shedding, suggesting a viral rebound. 
• Ferrets treated with both drugs saw similar clinical protection to baloxavir alone, but did not show signs of rebound. 

Note: Ferrets are a good, but not perfect, proxy for humans in influenza research, so these results may not be 100% applicable to humans.  

Today we've a new study- again from Webby & Jones et al. - this time using highly susceptible female BALB/c mice; which suggests that baloxavir outperforms oseltamivir, favipiravir, and amantadine in treating clade 2.3.4.4b (circa 2022) H5N1 avian viruses (in mice).

I've only reproduced the abstract and conclusion (reformatted for readability), so those wanting more specifics will want to download and read the PDF file. 

I'll have a bit more after the break.

Article Open access
Published: 19 February 2026
Baloxavir outperforms oseltamivir, favipiravir, and amantadine in treating lethal influenza A(H5N1) HA clade 2.3.4.4b infection in mice

Konstantin Andreev, Jeremy C. Jones, Ahmed Kandeil, Peter Vogel, Richard J. Webby & Elena A. Govorkova
Nature Communications , Article number: (2026) Cite this article

Abstract

Intercontinental spread of highly pathogenic avian influenza A(H5N1) viruses poses significant pandemic risks and necessitates strong protective countermeasures. 

We evaluated the therapeutic efficacy of the neuraminidase inhibitor oseltamivir, the polymerase inhibitors baloxavir and favipiravir, and an ion-channel blocker amantadine, against severe influenza A(H5N1) virus infection in female BALB/c mice. 

• Baloxavir (≥10 mg/kg, 1 dose) fully protected mice from death, significantly reduced virus respiratory replication, and prevented neuroinvasion. 
• Oseltamivir (≥100 mg/kg/day for 5 days) provided limited survival benefits, reduced lung titers but failed to prevent viral neuroinvasion. 
• Favipiravir (≥100 mg/kg/day for 5 days) provided partial protection, although did not reduce viral titers in lungs and brain. 
• Amantadine provided no benefits. 

Although all drugs inhibited A(H5N1) viruses in vitro, in vivo correlations did not extend beyond baloxavir. Our results indicate that baloxavir is the most reliable treatment to address both respiratory replication and systemic spread of contemporary A(H5N1) viruses in mice and should be considered in pandemic planning.

       (SNIP)

In summary, our study demonstrates that among four classes of influenza antivirals with wide or limited approval, only the polymerase inhibitor baloxavir provides consistent and robust protection and reduction in viral titers after lethal challenge with A(H5N1) clade 2.3.4.4b in mice.

The polymerase inhibitor favipiravir provided partial protection against both disease criteria. In contrast, oseltamivir afforded limited survival benefits and did not control viral titers. These results may in part be due to targeting the early steps of the viral replication cycle and may be of significance for A(H5N1) viruses that have increased polymerase activity. For amantadine and oseltamivir, we found little to no correlation between their antiviral efficacy in mice and susceptibility in vitro, confirming previously published data44. 

At present, we encourage prioritization of baloxavir or, potentially, baloxavir drug combinations as a potential frontline therapeutic approach for A(H5N1) clade 2.3.4.4b infections. We also suggest that more prognostic approaches are warranted to evaluate antivirals against emerging influenza viruses.  

       (Continue. . . )

Of note, this study used 4-year-old strains instead of more contemporary `Bovine' B3.13 or avian D1.1 genotypes, which together have caused dozens of human infections in the United States over the past 2 years.

Both of these 2022 H5N1 isolates, however, are "well-characterized" for producing 100% lethality and neurotropism in BALB/C mice; making differences in outcomes easier to identify. 

Hopefully, B3.13, D1.1 - and any future genotypes that emerge - will undergo similar testing as time permits, as the results could differ.  

Over the past year we've seen increased calls for a shift in pandemic antiviral strategy towards Baloxavir (or combination therapy), but most countries have invested heavily in oseltamivir, making any change likely slow in coming. 

Oseltamivir is now a generic drug, manufactured by at least a dozen companies, while Baloxavir is made only by Roche/Shionogi plants. The global supply of oseltamivir is probably 50 times greater than baloxavir, while the cost is roughly  1/10th. 

The reality is, even oseltamivir will be hard to get - at least during the first critical 24-48 hrs of infection - during a severe global influenza pandemic.

While I would be grateful for any antiviral (except, maybe Amantadine) in a flu pandemic, we will once again have to rely heavily on preventing infection; wearing face masks, hand washing, improved indoor ventilation, staying home while sick, and avoiding crowds.

Which is why I've already got my supply of masks, hand sanitizer, and OTC meds in the hall closet, and have stayed current with all of my vaccines.

If you aren't similarly prepared, you may want to revisit:

#Natlprep 2025: Personal Pandemic Preparedness

South Korea: MAFRA Detects ASF DNA in Pig Feed Additive as Outbreaks Increase (n=18)

 

#19,061

Just over a month ago (Jan 16th) South Korea reported their first African Swine Fever outbreak of 2026, and since then 17 more outbreaks have been reported across several provinces (Gyeonggi, Gangwon, Chungnam, Jeonbuk, Jeonnam, Gyeongbuk, and Gyeongnam).

This is triple what was reported by South Korea in all of 2025, and two weeks ago MAFRA ordered enhanced quarantine and biosecurity measures; with an emphasis on culling, quarantines, and disinfection of people and vehicles leaving farms.

African Swine fever is notoriously infectious, and the virus can remain viable for weeks or even months in the environment. Hence the strict rules on what you can't feed pigs; swill (kitchen scraps), imported meat, or contaminated forage. 

Most commercial farms today rely almost exclusively on commercial compound feed (typically corn/wheat/rice (60-80%) and soybean (15-25%) , along with nutritional additives like fats/oils & vitamins).

Many feed companies add heat-treated Spray-Dried Porcine Plasma (SDPP) as a "starter diets" for weaned piglets.  Only `healthy' donors animals supposed to be used, and this 80°C heat-treatment is designed to kill all possible infectious contaminants, including ASF or FMD. 

At least, that's the plan. 

Yesterday South Korea's MAFRA announced the detection of ASF DNA in at least two samples of stored porcine plasma; the first time that ASF genetic material has been found in a feed ingredient in Korea.

As this was a PCR finding, further tests will be required to determine if this was from dead DNA fragments or a live, and still infectious, virus.   

Given the gravity of this finding, MAFRA is assuming the worst; that these detections indicate a viable - and infectious - virus, and have ordered a nationwide ban and farmers holding contaminated feed must immediately incinerate or bury it. 

It will take a week or two before we know if these feed products actually contain infectious virus, and perhaps even longer to figure out where the system broke down.  

I've reproduced the (translated) MAFRA report below.  I'll have a brief postscript after the break.

Results of the (interim) epidemiological investigation into African swine fever and quarantine measures to prevent its spread.
2026.02.20 16:33:11 Foot-and-Mouth Disease Prevention Division, Quarantine Policy Bureau

The Central Disaster and Safety Countermeasures Headquarters for African Swine Fever ( Director Song Mei-ryeong, Minister of Agriculture, Food and Rural Affairs , hereinafter referred to as the Central Disaster and Safety Countermeasures Headquarters ) will confirm the situation of the outbreak of African swine fever (ASF) and the results of the epidemiological investigation on Friday, February 20, and will promote quarantine measures to prevent the spread .

1. Occurrence situation and quarantine measures

Since the first outbreak of African swine fever in Gangneung, Gangwon Province on January 16th of this year, a total of 18 cases have occurred* in Hwaseong and Pyeongtaek, Gyeonggi Province, and Cheorwon, Gangwon Province, as of February 19th . The Central Disaster and Safety Countermeasures Headquarters is currently taking quarantine measures , including culling and disinfection of farms where ASF has occurred , movement restrictions on quarantine areas and farms related to epidemiology , and surveillance and inspection , to prevent further outbreaks of ASF .

* Occurred in 2026 (18 cases ): 6 in Gyeonggi , 2 in Gangwon , 3 in Chungcheongnam-do , 2 in Jeollabuk-do , 2 in Jeollanam-do , 1 in Gyeongbuk , 2 in Gyeongnam

** Past occurrences : (`19) 14 cases → (`20) 2 → (`21) 5 → (`22) 7 → (`23) 10 → (`24) 11 → (`25) 6

 In addition, we are strengthening quarantine management , including nationwide inspections of pig farms , inspections of pigs shipped from slaughterhouses and environmental inspections , and crackdowns on the distribution and trading of illegal livestock products , to block further spread by analyzing recent outbreak patterns and causes and blocking factors of artificial transmission .

* ① ( Comprehensive farm inspection ) Comprehensive inspection ( carcasses , environment ) of pig farms nationwide , starting with breeding farms and general farms ; ② ( Inspection of shipped pigs ) In parallel with the comprehensive farm inspection , inspection of shipped pigs and environment at pig slaughterhouses nationwide (69 locations , 1,000 households ) using private organizations ; ③ ( Farm workers ) Environmental inspection of worker accommodations and goods , notification of farm workers and quarantine rules, and prohibition of gatherings and events ; ④ ( Illegal livestock products ) Prohibition of bringing in and storing illegal livestock products into farms , crackdown on illegal distribution and transactions, etc. 

2. Interim results of the epidemiological investigation

The Animal and Plant Quarantine Agency is conducting an epidemiological investigation into various risk factors, including farm products , farm workers, and illegal livestock products, to determine the cause of the sporadic outbreaks of ASF across the country .

This year, as the number of deaths of young pigs ( piglets ) has increased in farms where ASF occurred , unlike in the past, we have been focusing on investigating feed containing pig plasma proteins fed to young pigs , feed manufacturers ( suppliers ) , and feed raw material manufacturers .

* Feed on the farm where the outbreak occurred (142 cases ), feed suppliers (6 locations, 56 cases ), feed raw material suppliers (1 location, 26 cases ), feed raw material inspection agencies (2 locations , 68 cases )

During the intensive investigation, two ASF genes were detected * among stored samples requested by feed raw material ( porcine plasma protein ) manufacturers to feed raw material testing agencies .

* Detection of ASF genes means detection of virus segments , and whether it is an infectious virus requires further confirmation through experiments.

This is the first case in Korea where ASF genes were detected in feed raw materials . It is presumed that ASF- contaminated pig blood entered the feed supply chain , and the possibility of ASF being introduced through the supply of contaminated feed has been confirmed .

3. Key measures under the Livestock Infectious Disease Prevention Act

The central government will first have the local government's livestock quarantine officer instruct the owners of feed in which ASF genes have been detected at pig farms to take measures such as incineration or burial of the relevant items in accordance with the Livestock Infectious Disease Prevention Act * .

* Article 23 of the Livestock Infectious Disease Prevention Act ( Incineration of contaminated items, etc. )

In addition, as the ASF gene was detected in the feed raw materials, the Animal and Plant Quarantine Agency plans to disclose the information on the farm where the ASF gene was detected, along with the production date and raw material ingredients related to the detection , on the website of the Animal and Plant Quarantine Agency (www.qia.go.kr) in accordance with the Livestock Infectious Disease Prevention Act, and recommend that pig farms nationwide stop using the feed as a preventive measure .

* Article 3-2 ( Disclosure of information on the status of outbreak of livestock infectious diseases ) Paragraph 1 of the Livestock Infectious Disease Prevention Act , Article 2-2 Paragraph 1 Subparagraph 5 of the Enforcement Decree of the same Act , Article 3-3 Paragraph 2 Subparagraph 6 of the Enforcement Rules of the same Act

In addition, a nationwide inspection of pig farms is in progress , and if a pig farm is identified that used feed raw materials in which the ASF gene was detected, the farm in question will be inspected first to take measures to prevent the spread .

4. Key measures under the Feed Management Act

For businesses that are confirmed to have manufactured or sold feed that is confirmed to be contaminated with pathogens that cause disease in humans or animals , or that have used such feed as a raw material for feed, measures such as prohibiting the manufacture , sale , and use of such feed will be taken in accordance with Article 14 of the Feed Management Act .

In addition, we plan to consider administrative measures such as cancellation of manufacturing registration or suspension of business in accordance with Article 25 of the same Act , and imprisonment of up to 3 years or a fine of up to 30 million won in accordance with Article 33 .

In addition , if it is determined that feed inspection is necessary to ensure the safety and quality of feed, additional inspections will be conducted in accordance with Article 21 of the Feed Management Act . If a violation is confirmed , necessary measures to eliminate hazardous factors, such as an order to recall or discard the feed in question, will be ordered in accordance with Article 24 of the same Act. In addition, the fact of an order to recall or discard in accordance with Article 24-2 of the same Act will be announced .

4. Requests

Park Jeong-hoon , Director of the Food Policy Bureau at the Ministry of Agriculture, Food and Rural Affairs, said , “ This is the first case in Korea where ASF genes have been detected in feed raw materials , and it is presumed that ASF- contaminated pig blood has entered the feed supply chain. Therefore , we request that swift measures be taken in accordance with relevant regulations regarding the feed raw materials and related products . ”

In addition , he emphasized, “ Based on the results of epidemiological investigations , we plan to continue implementing measures to block the spread , so we ask for active cooperation from livestock farms , local governments, associations, and other related organizations . ”

Between 2018-2019 China suffered a catastrophic ASF outbreak - and while China officially reported < 2 million pigs lost - outside sources estimated their losses to be 100 times higher (see African Swine Fever In China: Epizootic or An EpicZootic?).

Pork prices in China tripled - when you could get it - and the virus eventually crossed over into Vietnam, North Korea, South Korea, Mongolia, Cambodia, Laos, Myanmar, and the Philippines.

All reasons why South Korea isn't waiting for the final test results before taking all possible steps to stop this outbreak. 

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

Transmission patterns between different hosts of  H6 viruses.

 
Credit: JOI: Prevalence and Transmission of Influenza A (H6) Viruses

#19,060

Last August, 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. 

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).

The CDC currently has this to say about H6 viruses: Avian Influenza A(H6) Viruses

LPAI A(H6) virus outbreaks in birds are not internationally reportable, therefore, its true prevalence is unknown. However, LPAI A(H6) viruses have been identified in various species of wild waterfowl and domestic poultry in Eurasia and the Americas. Known subtypes of A(H6) viruses include LPAI A(H6N1) and A(H6N2). In 2013, Taiwan reported the first known human infection with LPAI A(H6N1) virus.

While not a `reportable' disease, over the past several years we've seen growing interest by Chinese scientists over some of its recent evolutionary moves, including: 

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

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

That said, H6 viruses remain fairly far down our pandemic watch list, with H5N1 getting most of our attention, although it ranks 7th on the CDC IRAT List (see below).

In terms of likelihood of emergence, the CDC currently ranks a Chinese EA H1N1 `G4' swine virus at the very top of their list of zoonotic influenza A viruses with pandemic potential, with 2 other North American swine variant viruses and H9N2 scoring above H5N1.

While most (but not all) H9N2 infections have been relatively mild, it continues to evolve towards a more easily human transmissible virus (see EM&I: Enhanced Replication of a Contemporary Avian Influenza A H9N2 Virus in Human Respiratory Organoids).

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

All of which brings us to a new letter, published this week in the Journal of Infection, that reports on the detection and spread of a new H6N2 reassortment virus, which sports not only the NA gene from H9N2, but all 6 internal genes as well.

Although we haven't seen reports of human infection with this new reassortment (and the H6 HA retains avian characteristics), this wholesale replacement of 7 gene segments by H9N2 adds a number of known or suspected mammalian mutations to the mix. 

This new reassortant has been detected in poultry in several several provinces in eastern China at the end of 2025, suggesting it already well established. 

While none of this guarantees future greatness for this H6 reassortant, it is hard to imagine a better advantage, given H9N2's track record. I've just provided the link, and some excerpts from the correspondence. 

Click through to read the full report. I'll have a bit more after the break. 

Letter to the Editor

Zoonotic Threat of Novel H6N2 Avian Influenza Virus with Internal Genes Exclusively Derived from H9N2, China, 2025
 Kaituo Liu 1, Xiyue Wang 1, Jiehong Huang 1, Pan Liu, Yijia Sun, Wenhao Yang, Xiaolong Lu, Yu Chen, Jiao Hu, Min Gu, Xiaowen Liu, Shunlin Hu, Ruyi Gao, Xiaoquan Wang, Xiufan Liu

(EXCERPT)

In this study, we report the identification and characterization of a novel H6N2 reassortant virus isolated from poultry in Eastern China. Genetic analysis reveals that this virus possesses a hemagglutinin (HA) gene from circulating H6N6 waterfowl viruses, a neuraminidase (NA) gene from endemic poultry H9N2, and most critically, a complete set of six internal genes derived entirely from the H9N2 lineage, a genetic constellation known to potentiate cross-species infection8.

This represents the first natural detection of an H6N2 virus with an internal gene cassette exclusively derived from H9N2, and the virus has already achieved widespread circulation in in Eastern China (Jiangsu, Shandong, and Zhejiang provinces) poultry populations, indicating successful establishment.

The emergence of the novel H6N2 virus underscores the persistent and evolving threat posed by the co‑circulation of multiple subtype AIVs in China. Given that its molecular genetic profile indicates an elevated potential for cross‑species transmission, we strongly recommend that immediate enhanced and targeted surveillance, along with reinforced control measures in poultry and wild birds, should be implemented promptly to contain viral spread before human infections occur. 

(Continue. . . )

Admittedly, we've seen recent warnings from Chinese scientists on the spread of other, equally concerning, novel influenza A viruses, including last summer's Virology: Assessment of the Public Health Risk of Novel Reassortant H3N3 Avian Influenza Viruses That Emerged in Chickens).

While much of the news out of China is restricted, the impression is that both LPAI and HPAI viruses are spiralling out of control in Chinese poultry. 

Last November (see China MOA Announces New Guidelines to Expedite Animal Vaccine Strain Approvals ) China's MOA published a remarkable announcement - which tacitly admitted that many of their current animal vaccines (including against H9N2) were inadequate and/or suboptimal - and ordered major regulatory changes in order to accelerate updates.

This wasn't exactly a surprise, as previously, in NPJ Vaccines: Impact of Inactivated Vaccine on Transmission and Evolution of H9N2 Avian Influenza Virus in Chickens, we'd seen evidence that inactivated vaccines had failed to prevent - or even reduce - H9N2 in China's poultry, and they may have driven viral evolution (including mammalian adaptations).

While this report on H6N2 is concerning, it is part of a pattern we are seeing of increased diversity in avian influenza viruses circulating in China. While most of these reassortants are destined to fade into obscurity, it only takes one overachiever to put us back into pandemic mode. 

Stay tuned. 

New Jersey's Wild Bird Die-Off

 

#19,059

The Northern Hemisphere is at - or near - peak avian flu for this winter season, with literally scores of outbreaks being reported on a daily basis.  So much so, that reporting on individual outbreaks has become nearly futile. 

While we get reasonably accurate numbers of poultry lost to HPAI H5, its impact on wild birds and mammals can only be guesstimated. 

A year ago, in Nature Reviews: The Threat of Avian Influenza H5N1 Looms Over Global Biodiversity, we looked at some of those estimates:

An estimated half a billion domestic fowl have died of H5N1 (ref. 4), and this number is rising; mortality in wildlife is more difficult to quantify than in poultry, but the effects are substantial. By mid-2024, H5N1 infections were documented in at least 406 bird and 51 mammal wild species (according to reports on the World Animal Health Information System (WAHIS)), and available reports suggest that multiple millions of wild animal individuals may have died (Fig. 1a).

The most noteworthy mass-mortality events include more than 200,000 wild birds in coastal areas of Peru6; 24,000 sea lions in South America7; 20,500 wild birds in Scotland8; 6,500 Cape cormorants in Namibia9; and 17,400 elephant seals, including >95% of the pups in Argentina10. These figures, however, largely underestimate actual mortalities, owing to a pervasive lack of monitoring, testing and reporting — particularly in inaccessible areas and in disadvantaged countries4,7.

These numbers are now 18 months old, and H5's carnage has only increased since then (see ISIRV: Update on H5N1 Panzootic: Infected Mammal Species Increase by Almost 50% in Just Over a Year). While H5N1 has yet to crack the human code, it is already a devastating pandemic (panzootic) in animals. 

The long-term impact of this loss of biodiversity remains uncertain. By the time we know, however, it will be a fait accompli. 

Last week, in Several States Warn On Contact With Wild Birds/Mammals, we looked at a sampling of recent non-poultry outbreaks across the country. This week, the hot-spot (at least based on media reporting) for avian flu appears to be New Jersey. 

As the following FluTracker's Thread illustrates, over the past few days the NJ Department of Environment has been flooded with reports of hundreds of dead birds (mostly in Snow geese and Canadian geese) littered across the state. 

Credit NJ Fish & Wildlife

What Agencies are Responding to the Outbreak?

The U.S. Centers for Disease Control and Prevention  states that the ongoing nationwide H5N1 outbreak is primarily an animal health issue that poses low risk to the health of the public. The three principal state agencies involved in monitoring and responding to avian influenza are NJDEP Fish & Wildlife, the New Jersey Department of Health, and the New Jersey Department of Agriculture, which provide the following updates:

• Between August 2025 and February 17th,2026, we have confirmed detections in 8 counties (Bergen, Burlington, Middlesex, Monmouth, Salem, Somerset, Sussex and Warren) and a preliminary detection in 5 counties (Atlantic, Cape May, Cumberland, Essex, and Hunterdon).
• The New Jersey Department of Health  continues to closely monitor H5N1 and collaborate with state and federal partners on preparedness and response to H5N1. There are no reports of H5N1 in humans in NJ, but the virus has been detected in multiple domestic cats: H5 Highly Pathogenic Avian Influenza Confirmed in New Jersey Cat 
• The New Jersey Department of Agriculture  reports that there have been confirmed detections in domestic poultry in Hudson, Mercer, Union and Essex Counties.

While tests on these most recent bird deaths are pending, yesterday the Burlington County Department of Health Posted:

The Burlington County Health Department is reminding residents to be aware of the potential spread of Highly Pathogenic Avian Influenza, also known as bird flu, following the discovery of large numbers of dead geese in Hainesport and other South Jersey locations this week.

The Health Department has not been notified of any positive tests confirming the birds died from bird flu, however, officials are treating it as a likely bird flu case.

Residents are encouraged to review avian flu information and guidance on the County Health Department website and follow all recommended precautions. The webpage is at https://www.co.burlington.nj.us/2115/H5N1-Bird-Flu . Information is also posted in County parks.

Among the recommended precautions:

• Avoid contact with wild birds;

• Avoid unprotected contact with wild or domestic birds;

• Report cases of dead or sick wild birds to the NJ Dept. of Environmental Protection at 877-927-6337;

• Report cases of dead or sick domestic birds or livestock to the NJ Dept. of Agriculture at 609-671-6400 or state.veterinarian@ag.nj.gov .

• Pet owners should keep dogs and cats away from areas of high concentrations of geese or geese waste;

• Pet owners who notice signs of illness in their pet bird, cat, dog or any other domesticated animal should immediately contact their family veterinarian to safely examine your pet and test for bird flu if needed.

Additional guidance is available on the New Jersey H5N1 page at https://www.nj.gov/.../divi.../ah/livestockhealth/h5n1.shtml .

On Tuesday, the Borough of Pitman announced the closure of two parks on their Facebook page due to excessive bird deaths.

 This was followed up by a more detailed announcement:

It was just about a year ago, we were following the outbreak of H5N1 among colony of domestic cats on a property in western New Jersey (see Hunterdon County DOH Reports 4 More Cats Test Positive for HPAI H5N1 (Ttl=6)).

While we await test results, for now the NJ Fish and Wildlife Department is offering the following :

What Do You Do if You See a Group of Sick or Dead Wild Birds?

Please fill out the Wild Bird Disease Reporting Form .

How Do I Report Sick or Dead Domestic Birds?

If you are reporting sick or dead domestic poultry, please call the New Jersey Department of Agriculture Division of Animal Health at (609) 671-6400.

What if I Have Questions About Human or Domestic Pet Health Due to H5N1?

If you have questions about human or domestic pet health due to H5N1, please direct your questions to your local health department .

What are Disposal Options for Property Owners?

While NJ DEP Fish & Wildlife does not advise that the public handle sick or dead wildlife, if you have a dead bird on your property and are electing to dispose of the carcass, precautions should be taken:

• PPE should be worn, including gloves, a mask, and eye protection.
• Avoid direct contact between you and the animal by using a shovel to move the carcass.
• Double-bag each bird, close the bag using a zip-tie, and place in an outdoor trash bin inaccessible to pets and other wildlife.
• Following disposal, immediately wash your hands with soap and water and disinfect any non-disposable items using a diluted household bleach solution. Allow the disinfectant to sit on the item for 10 minutes before rinsing with warm water.

Residents can also contact their local municipality or county to inquire about animal control services or private wildlife control services able to dispose of dead wildlife.

Sage advice, assuming anyone is listening.   

When You're in the Market For Bird Flu

 
Based on USDA Data - Graph created with Gemini

#19,058

Since the arrival of H5N1 in late 2021, the USDA has reported 64 outbreaks in live bird markets (LBMs) across 6 states (NY, NJ, PA, FL, VA, CA), with 10 outbreaks reported over the past 60 days.

While outbreaks in live bird markets continue to be reported to the USDA, they appear to be getting far less press coverage than they were a year ago. 

The link between live bird markets and the spread (and potential reassortment of) avian flu strains has been long established. LBMs typically bring together birds of varying species (chickens, ducks, geese, quail, and others) - often imported from different farms - which are housed in cramped quarters. 

A dozen years ago, in CDC: Risk Factors Involved With H7N9 Infection we looked at a case-control study conducted by an international group of scientists, including researchers from both the Chinese and the US CDC that concluded.

Exposures to poultry in markets were associated with A(H7N9) virus infection, even without poultry contact. China should consider permanently closing live poultry markets or aggressively pursuing control measures to prevent spread of this emerging pathogen. 

In 2016's Interventions in live poultry markets for the control of avian influenza: A systematic review Vittoria Offeddu , Benjamin J. Cowling, and J.S. Malik Peiris laid out the risks of avian influenza from live bird markets, reviewed some of the possible interventions, and concluded: 

Highlights

• Avian influenza viruses (AIVs) can infect humans. Bird-to-human transmission is particularly intense in live poultry markets.
• Periodic rest days, overnight depopulation or sale bans of certain species significantly reduce AIV-circulation in the markets.
• Market closure would lastingly reduce the risk of animal and human infection.

Admittedly, practices and hygienic standards vary greatly between countries, but last summer in J. Virology: Zoonotic Disease Risk at Traditional Food Markets (Minireview), we looked a review that cautioned that `. . . their sustainability and safety depend on integrating evidence-based strategies to mitigate zoonotic disease risks.'

While less common here than in Asia and the Middle East, the United States has hundreds of live bird markets, clustered primarily in the mid-Atlantic region (see Live Bird Markets of the Northeastern United States by Jarra F Jagne, DVM et al.)

Live bird markets serve mainly ethnic immigrant populations in large urban centers of Northeastern states. The markets are important in the epidemiology of avian influenza viruses (AIV) especially H5 and H7 strains that have zoonotic potential and an effect on trade with United States trading partners.

Until four years ago, HPAI H5 was not endemic in North America, which greatly reduced (but didn't completely eliminate) the risks of avian flu transmission in U.S.  live bird markets (see 2016's H5 Avian Flu Reported In NE U.S. LBMs (Live Bird Markets) - UPDATED).

Over the past few years the threat from H5N1 has grown markedly in the Western Hemisphere. So far, the strains of HPAI H5 in the United States have been generally milder in humans than those seen in Asia and the Middle East, but serious illnesses and deaths have occurred, and further increases in virulence are possible. 

 

Practices (like fur farming, drinking raw milk, letting your cat run free outdoors, or working at or visiting an LBM) - that were once presumably less dangerous  - are arguably more dangerous now. 

But we resist adapting to - or preparing for - new threats like avian flu because of the `Normalcy bias', the belief that tomorrow will be more-or-less like yesterday. We cling to the notion that all future changes will be small, incremental, and manageable. 

While that may bring comfort, and a sense of stability, it also brings risk. 

Whether HPAI H5 has the `right stuff' to spark a pandemic is unknown. But somewhere out there, the next pandemic virus is honing its skills.  And our laissez faire attitude towards pandemic prevention and preparedness will eventually prove costly.