Avian Flu Diary: JOI: Prevalence and Transmission of Influenza A (H6) Viruses Pose a Potential Threat to Public Health

#18,449

Among the panoply of avian flu viruses, H5 and H7 viruses get the bulk of our attention, since they are the most destructive to the poultry industry and are known to occasionally spontaneously mutate into HPAI viruses when allowed to circulate in poultry.

There are dozens of other subtypes (H1Nx-H16Nx) that are not considered `reportable' by WOAH, yet still have some zoonotic properties (Note: H17 & H18 viruses have been reported in bats).

After all, a reassorted H3 avian virus sparked the 1968 H3N2 pandemic, and has remained in constant circulation in humans for nearly 60 years, as did a reassorted H2 avian virus in the late 1950s.

While trying to predict which novel flu will spark the next pandemic is a mug's game, we do try to track activity that may indicate a virus's progress in that direction.

A few contenders (excluding H5, H7, and swine variant flu viruses) include:

Recent spillovers into humans, rapid spread, and robust reassortments of avian H3 in China has some researchers worried (see Frontiers Microbiology: China's Growing Concerns Over The H3 AIV).
LPAI H9N2 - which is poorly controlled by vaccines - has caused > 140 (mostly mild) human infections (see Nature: Genetic diversity of H9N2 avian influenza viruses in poultry across China and implications for zoonotic transmission).
And we've seen a smattering of H10 infections as well (see Frontiers: Phylogenetic and Mutational Analysis of H10N3 Avian Influenza A virus in China: Potential Threats to Human Health).

One of the lower-profile subtypes we've been watching for the past dozen years are A(H6) viruses, which made headlines in 2013 and 2014 after a college student was hospitalized with pneumonia, and several dogs were found infected in Taiwan.

Taiwan CDC: Epidemiological Analysis Of Human H6N1 Infection

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.

Over the past 12 years we've seen a number of studies suggesting that H6 viruses may be better adapting to mammalian hosts, 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

All of which brings us to a new report - published last week in the Journal of Infection - which highlights that H6 viruses are widespread, genetically diverse, capable of mammalian spillover, and pose a growing threat to public health.

While a relatively brief report, I've only posted some excerpts. Follow the link to read it in its entirety.

Prevalence and Transmission of Influenza A (H6) Viruses Pose a Potential Threat to Public Health

Xingdong Song 1, Xiaohong Hou 1, Yue Li, Ruihua Zhang, Yu Meng, Yanli Zhu, Liangmeng Wei, Shijin JiangShow more

https://doi.org/10.1016/j.jinf.2025.106594

Dear Editor,

On March 25, 2024, the clade 2.3.4.4b highly pathogenic influenza H5N1 virus infection was reported in dairy cattle in Texas, USA. As of June 7, 2025, outbreaks of H5N1 virus occurred in more than 1000 dairy farms across 17 states, with a mortality rate of up to 10% in infected cattle. Additionally, the H5N1 virus caused 41 confirmed human infections among dairy workers in 2024.1 Highly pathogenic influenza viruses pose a persistent threat to global public health, while the potential risks of low pathogenic influenza viruses should not be ignored.

Recently, we read with interest the articles published in the Journal of Infection regarding human infections with low pathogenic H3N8, H7N4, H9N2, H10N3, H10N5 and H10N8 subtype influenza viruses.2, 3, 4, 5, 6, 7 In addition to the aforementioned subtypes, the H6 subtype influenza virus has also garnered significant attention from the scientific community.

It is reported that H6 subtype viruses were widely circulating in various avian hosts, including wild, domestic aquatic and terrestrial bird species. Notably, some H6 viruses could cross species barrier to infect mice and ferrets without prior adaptation, and even acquired the ability to bind to human-type receptors.

Furthermore, a serological analysis targeting individuals with occupational exposure to poultry in China demonstrated that among 15689 serum samples collected from 22 provinces across mainland China, 63 tested positive for H6 avian influenza virus (AIV). Strikingly, the first human case with H6N1 subtype AIV infection was reported in Taiwan region, China in 2013.8

These data indicate the extensive host range that the H6 virus can infect, and the virus has resulted in spillover events, posing a potential threat to public health security.

(SNIP)

Furthermore, we evaluated the global migration of H6 viruses, and identified 14 credible migrative routes, with North America, East Asia and South Asia implicated in seven, six and five supported dispersal routs, respectively, indicating their central roles in viral dissemination (Fig. 2C).

In addition, there were four decisively supported routes with BF larger than 1000 (Table S3), including two routes from China to East Asia and South Asia, then from East Asia to Russian Federation, and from South Asia to Europe. It is worth noting that the H6 viruses from North America contributed to the transmission of the viruses to China, with the BF of 53.9726.
In conclusion, our research findings provide new insights into the geographical distribution and transmission routes of global H6 subtype viruses. With the continuous transmission and expanding geographical distribution of H6 viruses, their potential threat to public health security have become impossible to ignore, and we recommend that active and comprehensive surveillance of H6 viruses should be strengthened.

(Continue . . . )

None of this is to suggest that H6 is an imminent pandemic threat, only a plausible one. Of course, there are myriad other ways the next pandemic could emerge.

A year ago the WHO Released their 2024 Pathogens Prioritization Report, which identified 34 priority pathogens from 16 families (see graphic below).

Sadly, the recent dismantling of our global surveillance, reporting, and response systems following the declaration of `victory' over COVID suggests we haven't learned the primary lesson from the last pandemic;