Monday, October 09, 2017

Avian Flu: That Was Then . . This Is Now


Since both seasonal and avian influenza follow a seasonal pattern, here in the Northern Hemisphere we tend to think of October as the start of a new flu `year'. That's when China resets their yearly H7N9 counts, poultry interests begin to ramp up their biosecurity, and when the CDC, ECDC, and other public health agencies begin tracking seasonal flu in earnest.
As the map above attests, over the past 12 months Asia, Africa, Europe, and the Middle East have been hit particularly hard by avian flu - while North America, South America, and Australia/NZ have been largely spared. 
While telling, what this map doesn't show is how the H5N8, H5N6, and H7N9 viruses have  changed - both genetically, geographically, and behaviorally - over the past year.  While we've covered all of these changes in past blogs, it is easy to forget how much different the bird flu threat appeared just 12 months ago.

Therefore, with `Then'  meaning late summer 2016, a brief comparison.

H7N9 Then

While certainly still on our radar screens, reports of H7N9 cases in China had been on a steady decline since the winter of 2013-2014.

During the summer of 2016, we saw a smattering of late season cases (see China: 5 H7N9 Cases In July), and in May a study (see EID Journal: Human Infection With H7N9 During 3 Epidemic Waves - China) identified a few minor behavioral changes in the virus, but for the most part H7N9 appeared to be a virus still struggling to get a foothold in China. 

H7N9 Now

Beginning in December, H7N9 literally exploded in China, with nearly as many cases (n=766) reported over the next 6 months as had been reported in the first four epidemic waves combined. 
Geographically,  H7N9 spread to 8 new Provinces in China over the past 12 months, and Macao reported their first local infection.
Driving this impressive surge have been substantial genetic changes in the virus, including the emergence (and dominance) of a new lineage (Yangtze River) and a rapidly spreading HPAI version of the virus.

While data is limited, there is some evidence to suggest this HPAI version may pose more of a threat to humans than the LPAI version (see Eurosurveillance: Epidemiology of Human HPAI H7N9 Infection - Guangdong Province).

We've also seen reports that up to 10% of human infections have shown resistance to one or more NA inhibitors (see MMWR Report), and plans for the development of a new Candidate Vaccine Virus (CVV) by the the WHO to address these evolutionary changes.

Over the past couple of months we've seen an avalanche of new studies on H7N9, none of which are particularly reassuring:
J. Virology: Genesis and Spread of Newly Emerged HPAI H7N9 In China

J. Infect. Diseases: Human Clusters Of H7N9 In China - March 2013 to June 2015
Sci. Repts: Adaptation of H7N9 in Primary Human Airway Epithelial cells
Obviously worried, for the very first time, China's MOA Ordered An HPAI H7N9 Vaccine Deployed Nationwide This Fall.

While H7N9 hasn't managed to adapt well enough to human physiology to transmit efficiently, the CDC's IRAT system ranks the newly emerged Yangtze River Delta lineage along with the original Pearl River Delta Lineage (see Updating the CDC's IRAT (Influenza Risk Assessment Tool) Rankings) at the top of their list of viruses with the greatest pandemic potential.

All things considered, this has been a remarkable turn around for H7N9.

H5N8 Then

After emerging on the world stage in January of 2014 in South Korea, H5N8 forced the culling of 15 million chickens over the next three months.  From there, H5N8 spread into China - and the following fall turned up in Russia and Europe - and sparked the largest avian epizootic in North American history.
By the summer of 2015, H5N8 had vanished outside of Asia (see PNAS: The Enigma Of Disappearing HPAI H5 In North American Migratory Waterfowl). While still causing losses in Korea and China, to everyone's surprise H5N8 did not return the following winter to Europe or North America.
While highly pathogenic in poultry, H5N8 was notable for causing relatively few wild bird deaths, and the virus appeared short-lived in the environment. Best of all, H5N8 - unlike H5N1 and H5N6 - showed no signs of infecting humans.

H5N8 Now

Over the summer of 2016 we saw reports of H5N8 detected at Ubsu-Nur Lake, Russia in wild and migratory birds (see FAO/EMPRES: H5N8 Clade Detected Over Summer In Russia), followed by reports of H5N8 turning up first in India, and then Kazakhstan  in mid-October.

In late October (see FAO Notification Of H5N8 In Hungary) H5N8 returned to Europe. Three weeks later, on Nov 19th, in the WHO: Assessment Of Risk Associated With HPAI H5N8, we get the following description of its remarkable spread.
Since June 2016, countries in both Europe and Asia have detected infections in wild birds and/or domestic poultry with A(H5N8) including Austria, Croatia, Denmark, Germany, Hungary, India, Israel, Netherlands, Poland, Russian Federation and Switzerland. Many of these recent detections were associated with mortality in wild birds.
By the end of November H5N8 would have arrived in Iran, EgyptFinland, Sweden, and the Ukraine. Beyond its rapid geographic spread, H5N8 was also making headlines for its Unusual Mortality Among WIld Birds - a distinct change in its behavior over previous years. 

Over time we would discover that before the H5N8 arrived it had reassorted - either in Russia or China (see EID Journal: Reassorted HPAI H5N8 Clade - Germany 2016) - picking up virulence in wild birds, an expanded avian host range, and most recently, unusual environmental persistence into the summer.  
By spring H5N8 had hit wild birds and poultry in nearly every European country, and had spread into West Central and Central Africa.  By summer, it had made it - for the very first time - into the Southern Hemisphere (Zimbabwe & South Africa) where it continues to spread. 
While H5N8 still remains only a health threat to wild birds and poultry, there are increasing concerns (see J. Virulence Editorial: HPAI H5N8 - Should We Be Worried?) that H5N8 could someday acquire the genetic changes that would make it a human health threat as well. 

After nearly disappearing for 18 months outside of Asia, H5N8 over the past 12 months has grown to become the dominant HPAI virus around the globe.

H5N6 Then

Emerging in the spring of 2014, just months after H5N8, H5N6's range had remained confined mostly to China, with occasional outbreaks in Vietnam and Laos.  Roughly 15 human infections - all in China - had been reported over 2 years, with more than a 50% fatality rate.

Despite its ability to infect humans, and a growing genetic diversity (see Cell Host Microbe: Genesis, Evolution and Prevalence of HPAI H5N6 In China), H5N6 had shown far less ability to spread via migratory birds than had H5N1 and H5N8.

H5N6 Now

At the same time that H5N8 was conquering Europe, H5N6 suddenly arrived - first in South Korea - and then in Japan in November of 2016.  As with H5N8, H5N6 appeared to be spreading easily via migratory birds, and as we saw in Europe, wild bird deaths were suddenly widely reported in Japan and South Korea.
South Korea took the brunt of last winter's H5N6 epizootic (300+ outbreaks), but Japan reported hundreds of wild bird and environmental detections, and about a dozen poultry outbreaks. Over the winter Taiwan reported H5N6 outbreaks, and this summer the virus arrived in the Philippines
After two-plus years of being China-bound, H5N6 has begun to follow in the footsteps of H5N8, spreading easily via migratory birds.   While we've not seen any human infections reported since November of 2016, the virus is constantly evolving (see Virology: Five Distinct Reassortants of HPAI H5N6 In Japan - Winter 2016–2017) and so there are no guarantees that streak will last.

This new found mobility now has experts in Europe wondering whether H5N6 will one day follow both H5N1 and H5N8 and make its way across Asia and into Europe  DEFRA's: HPAI H5N8 In Europe - Update #15) noted last week:
This year, the cases in wild birds and poultry are already occurring. It is also important to note the pattern of H5N8 HPAI emergence in 2014 when the virus was observed in Japan and South Korea in wild birds and a few months later it was detected in Europe and North America.
If the same pattern of wild bird transmission occurs this year, we might expect to see expansion in the range of H5N6 HPAI potentially to similar areas, as it was reported in high numbers of migratory wild birds in Japan over the summer together with waves of infection in poultry in the Republic of Korea. This virus has some affinity for human cells unlike H5N8 HPAI virus, therefore public health issues will also need to be considered carefully.
These are only a few highlights from an incredibly busy bird flu year. But any way you figure it, the past 12 months have seen remarkable changes in our top avian flu threats.
What all of this portends for this winter is unknowable. As is suggested by the absence of human infections from H5N6 over the past year, evolution doesn't  always move toward greater virulence.
But what it does tell us is that we can't assume that these pathogens - and others - will behave tomorrow the same way they behaved yesterday. With viruses, the only constant is change. 
And we need to be prepared to deal with those changes, which ever way they go.

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