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The H5N8 Bird Flu and Why We Should Pay Attention

Before COVID, reports of a new bird flu trickling or even sweeping out of Asia didn’t garner much attention. That’s certainly changed. So when two members of the China Novel Coronavirus Investigating and Research Team, who co-authored the first warning of what was to come in February 2020 in The New England Journal of Medicine, sound a new alarm, maybe we should listen.

In a short Insights Perspective published in Science, “Emerging H5N8 avian influenza viruses,” Weifeng Shi and George Gao make the case for concern that a bird flu now in more than 46 countries across Europe, Asia, and Africa has jumped to humans. Only seven poultry farm workers in Russia were reported to have gotten sick, while trying to contain an outbreak among their feathered charges. But there must have been a time, in the fall of 2019, when COVID, too, had sickened only a few people.

An avian influenza virus would need to pass easily from person-to-person to seed a pandemic in people, like SARS-CoV-2 does. That’s unlikely, but as we’ve learned, not impossible.

Anatomy of a Flu Virus

An influenza virus has a more complex surface than the spike triplets of SARS-CoV-2. “H,” “N,” and numbers are shorthand to describe the surfaces of varieties of the more common A strain of influenza.

A flu virus is festooned with two types of glycoproteins (proteins with attached sugars). One type, hemagglutinin (HA), comes in 16 varieties and many subtypes within those varieties (“clades” and “subclades” in the lexicon). The other, a neuraminidase (NA), has nine types. The HAs look like spikes; the NAs resemble lollipops.

The 1918 Spanish flu and the swine flu of 2009 were H1N1. Bird flus are H5. Thousands of influenza epidemics that have wiped out bird populations have been documented since 1878.

Flu viruses reinvent themselves frequently, through point mutations that alter an individual RNA base (“drift”), as well as through larger-scale, fast recombination events that swap gene segments (“shifts”). SARS-CoV-2, in contrast, begets new variants with combinations of point mutations and small deletions, such as two RNA bases.

New viral variants are concerning because they can alter transmissibility, pathogenicity, and the host’s immune response. We modify vaccines to keep up with the natural mutation of viruses.

To cover multiple bases, flu vaccines consist of two types of influenza A and one type of influenza B. Conventional flu vaccines focus on a part of the hemagglutinin that the immune system recognizes as a stimulus to churn out antibodies. Efforts to create a more universal flu vaccine have been in the works since the 1930s. Candidates target the shared parts that don’t change, such as the stalks that support the hemagglutinins.

The New Bird Flu

Shi and Gao present a family tree of the H5 flu virus currently sweeping large swaths of the planet and deduce where it came from. Researchers glimpse viral evolution by comparing genome sequences, limited of course by what we notice.

The current “highly pathogenic avian influenza virus” – HPAIV in the lingo – began with an H5N1 variant striking chickens in Scotland in 1959. A strain of H5N1 that killed geese in Guangdong, China in 1996 joined and has taken off, diversifying, especially since 2010.

By 2013, the virus had mutated itself into H5N8 in Zhejiang, China, and then appeared in Russia and several other European countries. It reached Canada by the end of 2014, thanks to birds migrating along the Bering Strait that August. Then H5N8 emerged anew in Russia, Mongolia, Europe, India, and China. Meanwhile, H5 flu viruses paired with N2, N3, N6, and N9 also appeared in various places.

Tracking the trajectory of flu among migratory birds in Japan reveals how fast the situation can change.

In October 2020, researchers from Hokkaido University reported in the journal Viruses evidence of H5N8 in droppings in a lake from migratory birds. By late March 2021, more than 30 new outbreaks among domestic poultry and wild fowl had been reported in Japan, traced to migratory birds from Europe.

Sick birds flying from Europe to Japan was unusual for two reasons: new flus usually come from East Asia, and it all happened in just a few months. Plus, the European H5N8 variant is a bit different. A few of the single-RNA-base mutations alter the encoded amino acids in ways that make the virus bind more tenaciously to the sialic acid receptors on cells of the human lower airways. That might explain why, so far, the variant viruses don’t pass from person to person – buried deep in the lungs, they’re less likely to spew out in a cough or sneeze. But the infected person suffers severe respiratory distress.

Justifiable Fear?

Taken together, it’s clear that new bird flu viruses are all over the place, flown from here and there, perhaps mixing themselves into dangerous new variants.

Even if we can’t chart all the outbreaks, they appear to now be continuous and spreading, perhaps setting the stage for a pandemic should they meet and merge into a frightening confluence. And with a virus as inherently changeable as influenza, and as deadly as the H5N8 bird strains, could a new ability to pass person-to-person seed another pandemic? This time of flu?

That’s what Shi and Gao fear: “The zoonotic potential of AIVs warrants continuous, vigilant monitoring to avert further spillovers that could result in disastrous pandemics.”

They cite their reasons:

“Because of the long-distance migration of wild birds, the innate capacity for reassortment of avian influenza viruses, the increased human-type receptor binding capability, and the constant antigenic variation of HPAIVs, it is imperative that the global spread and potential risk of H5N8 avian influenza viruses to poultry farming, avian wildlife, and global public health are not ignored.”

They suggest that we:

• Rev up surveillance of the highly pathogenic flu viruses on poultry farms and in wild bird populations
• Learn more about the transmissibility, pathogenicity, and effect on the human immune response of one particular subtype of H5N8 (2.3.4.4b), and update vaccines
• Decrease small-scale family-based poultry farming and increase large-scale farming, and better manage live poultry markets
• Avoid wild birds, don’t hunt or eat them, and maintain public health measures during flu season

Don’t put away those COVID masks just yet! And get vaccinated, against COVID as well as flu.

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