Wednesday, June 22, 2022

The Lancet: Resurgence of H5N6 Avian Influenza Virus in 2021 Poses New Threat to Public Health


Although reports of new cases from China have fallen eerily silent in recent weeks, over the past 18 months we've seen a huge resurgence in human infection with avian H5N6 in China.  This virus is particularly concerning due to its high fatality rate in humans. 

While likely an under count, between 2014 and 2020 China had only reported 3 to 4 cases a year, but that number soared by more than 50 cases since December 2020.  

Since China has not reported a concurrent jump in H5N6 outbreaks in poultry, there are reasons to believe the virus may be spreading stealthily in vaccinated birds, from which it occasionally jumps to humans.  

Over the past year we've looked at a number of studies and reports on the continual evolution of H5N6, and its increasing threat to public health, including:

EID Journal: Epidemiologic, Clinical, and Genetic Characteristics of Human Infections with Influenza A(H5N6) Viruses, China

China CCDC Weekly: Genetic Characterization of Two Human A (H5N6) Viruses — Guangxi , China, 2021

CCDC Weekly: Outbreak Report - Five Independent Cases of Human Infection With HPAI H5N6 — Sichuan Province

Over the past 8 years H5N6 has been busy reinventing itself via antigenic drift and antigenic shift (reassortment), so that now there are numerous `flavors' of H5N6 co-circulating in China and Southeast Asia. Some are more pathogenic than others, but all continue to evolve

Eight months ago the CDC Added A New H5N6 Avian Flu Virus To Their IRAT List of zoonotic influenza viruses with pandemic potential.  While this particularly dangerous HPAI H5 virus has only been reported in China and parts of Southeast Asia, the concern is that it could eventually expand its geographic horizons the way that H5N1 and H5N8 have previously. 

All of which brings us to a new correspondence - printed yesterday in The Lancet  - where Chinese researchers offer some of the starkest warnings about the evolution of H5N6 we've seen to date. 

 Follow the link to download the Supplementary PDF, I'll have a brief postscript after the break. 

Resurgence of H5N6 avian influenza virus in 2021 poses new threat to public health

Jiahao ZhangHejia YeYi Liu , Ming LiaoWenbao Qi
Open Access  Published:June 21, 2022

First identified as belonging to the H5N1 subtype in Guangdong province, China, in 1996, the Gs/GD lineage H5 avian influenza viruses have continuously evolved and spread since.1,2

H5 subtype viruses evolved into multiple distinct subclades, among which has become dominant in China,3 and H5N6 viruses of this subclade led to an apparent increase in human infections in 2021 and 2022. During this period, 33 cases (of a total of 76 recorded cases infected with subclade H5N6 viruses) have been documented, resulting in 11 deaths and posing an alarming threat to public health.1

Almost all confirmed cases were in individuals who had reported exposure to poultry. To address concerns regarding the sharp increase in the number of human infections, we explored the evolutionary dynamics and conducted a risk assessment of H5N6 viruses from birds in live poultry markets during 2021.
In 2021, 5883 cloacal and tracheal swab samples from chickens, ducks, and geese were obtained from live poultry markets in China and analysed for influenza viruses (appendix pp 9–13). We determined the full-length genomes of 19 H5N6 viruses from chickens, ducks, and geese and found that the genomes of these viruses were more complex than those of H5N6 viruses circulating in China previously (appendix pp 2–3). 

Of particular concern is that the genomes of all H5N6 viruses were continuously reassorted with those of H5N8 viruses of wild bird-origin, and were genetically closely related to the H5N6 virus that infected humans in 2021 (appendix pp 2–3, 14–28). We found that these H5N6 viruses were novel reassortants. The HA and M genes of all isolates were derived from H5N8 viruses of wild-bird origin, whereas other internal genes of all isolates exhibited several separate clusters. On the basis of phylogenetic trees, we identified five distinct genotypes of H5N6 viruses (G1–G5; appendix pp 3, 28), and found that both the G1 and G3 genotype H5N6 viruses were 100% lethal to mice (appendix pp 3–4, 28–29).

The high genetic diversity and the virulence in mammals of H5N6 viruses in 2021 pose an increasing threat to public health. During the 2020–21 influenza season, novel H5N8 viruses repeatedly entered Europe, Russia, South Korea, and China, causing numerous outbreaks in wild birds and poultry.4 

Notably, these H5N8 viruses infected humans in Russia,5 highlighting the increasing threat to humans posed by the co-circulation of H5N6 and H5N8 viruses. Wild waterfowl are regarded as natural reservoirs that contribute to the global spread of avian influenza viruses through long-distance migration.14 Frequent contact with wild birds remains the most probable cause of viral introduction into domestic poultry. Countries in the Middle East, Europe, and Asia have a particularly important role in the global dissemination of influenza viruses.4

The co-circulation of H5N6 and H5N8 viruses in migratory birds accelerated the evolution of novel variants. Nowadays, clade H5 influenza viruses are widely prevalent in China. However, based on our assessment, the circulating H5N6 viruses are antigenically distinct from the strains in the commercial vaccine in China (appendix pp 3–4, 29), suggesting that these novel viruses will continue to circulate in poultry if the commercial vaccine is not updated.

The ongoing 2021–22 wave of avian influenza, which involves not only H5N6 but also the current outbreak of H5N1 viruses, is unprecedented in terms of its rapid spread and high frequency of outbreaks in birds, and poses a continuous threat to public health.

          (Continue . . . )

Nine years ago HPAI H5 appeared to have run its course, and for about 5 years China's H7N9 virus took center stage.  A successful H5+H7 poultry vaccination campaign in China in 2017 put the brakes on that outbreak as well, but flu viruses have an irritating habit of evolving faster than vaccines can be updated. 

With so many diverse and highly promiscuous H5 viruses co-circulating in China - apparently no longer well controlled by their vaccine - the potential for an inopportune reassortment event grows greater with each passing day.

Even though China's government is often slow to announce cases, over the past year we've seen ample expressions of concern from Chinese scientists. 

And if they are worried, we need to be paying attention.