Monday, February 13, 2017

A New Avian Flu Review

Credit NIAID












#12,221

Two years ago, in An Avian Flu Primer, I counted down the top avian flu threats around the world.  Since then we've seen a number of changes in the field. So today an updated look at our current crop of avian flu subtypes around the globe. 

Up until four years ago, if you mentioned `bird flu', it was pretty much assumed you were talking about HPAI H5N1, which emerged in China (for the second time) in 2003, and began spreading beyond Southeast Asia in 2005.
There were other (mostly LPAI) avian viruses out there, but none had the kind of impact on poultry - or the pandemic potential - of H5N1.

H5N1's dominance remained unchallenged until the spring of 2013, when we saw  the sudden emergence of H7N9 (curiously a Low Path virus in birds), followed in less than a year by H10N8, H5N8 and H5N6.

While H10N8 has receded (at least for now), H5N8 and H5N6 have thrived, expanding their geographic range, spinning off new genotypes (and subtypes), and evolving into even greater threats. 

The field has become so crowded that keeping track of all of these subtypes can be difficult, even for those of us who follow avian flu on a daily basis.

So, with the caveat that things are moving so quickly that this blog post may be obsolete before the pixels on your screen completely dry, I've put together a short primer on each of the `big four' avian flu viruses we are currently tracking.


H5N1



The O G (original gangster) of avian flu, H5N1 emerged in 2003 and made it to Western Europe, West Africa, India, and the Middle East by 2006 - but began a slow pullback in 2008 - leaving only a few pockets of activity outside of Asia (primarily Indonesia and Egypt). 

Along the way this virus has managed to infect at least 850 people (killing more than half) in 16 countries, although these `official' numbers are almost certainly a significant under count.  Egypt's 2015 outbreak saw at least 160 cases (see EID Journal: H5N1 In Egypt), making it the biggest human epidemic to date. 

While some clusters have been reported, H5N1 remains difficult to spread from human-to human.

That said, the H5N1 virus (like the others we will look at) continues to evolve (see Eurosurveillance: Emergence Of A Novel Cluster of H5N1 Clade 2.2.1. 2 and V. Sinica: HPAI H5N1 Clade 2.3.2.1c Virus in Migratory Birds, 2014–2015) and continues to increase in diversity (see chart below).


Differences in virulence and transmissibility exist between these clades, subclades, and genotypes which may help explain the difference in impacts we've seen over time, and around the world (see Differences In Virulence Between Closely Related H5N1 Strains).
 
Reporting from China, Egypt, and Indonesia are spotty at best, but the virus remains most active in those countries, along with parts of the Middle East (notably Iran & Iraq) and Western Africa where it returned in 2014 after an absence of 7 years. 

While seemingly taking a back seat to some of the newer entries in our bird flu field, H5N1 - after appearing to be on the decline for a few years - has been on the ascendant since around 2014 and remains a pandemic threat. 


H7N9 


Despite a 10 year head start, in four short years H7N9 has overtaken (and this year, blown the doors off) H5N1's lead in reported human infections.  Still confined to Mainland China, this LPAI (low path) virus in birds has proven quite deadly in humans, exacting a 40% mortality rate among known cases. 

Tracking and eradicating H7N9 in wild birds and poultry is extremely difficult, as this virus - unlike the others on our list - does not sicken or kill birds.  Often our first hint of local poultry infection comes when humans start falling ill. 

Like with H5N1, the true number of infections is unknown, as only the `sickest of the sick' are ever hospitalized and tested.  We've seen estimates from researchers at the University of Hong Kong that the actual number of H7N9 cases may be anywhere from 10 to 200 times greater than are detected and reported by China's surveillance (see Beneath The H7N9 Pyramid).

Like H5N1, H7N9 has become genetically diverse, reassorting (particularly with H9N2), and producing dozens of new genotypes (see Nature: Dissemination, Divergence & Establishment of H7N9 In China).  Still only reported in China, the risk of seeing this virus exported to neighboring countries is a very real and ongoing concern.
While apparently more easily transmitted from live birds to humans than the other avian flu subtypes we've seen, thus far we've seen no evidence of sustained or efficient human-to-human transmission of the virus.
But as we saw two weeks ago, in  Updated CDC Assessment On Avian H7N9 , `of the influenza viruses rated by the Influenza Risk Assessment Tool (IRAT), H7N9 is ranked as having the greatest potential to cause a pandemic, as well as potentially posing the greatest risk to severely impact public health.'

All of which makes this year's record setting pace of human infections in China something we are watching closely. 
 


H5N8/H5N2/H5Nx




While our next entry started off as a single subtype (H5N8) - emerging significantly for the first time in South Korea in January of 2014 - it has shown a remarkable ability to reassort with other avian viruses, spinning off new subtypes (H5N2, H5N1, H5Nx) that carry its parental clade 2.3.4.4. H5 surface protein.
After a spectacular 2014-2015, which saw it spark North America's largest avian epizootic and cause sporadic outbreaks in Europe, it was a practically no-show for the 2015-2016 winter season.
Over the summer of 2016, however, H5N8 appears to have reinvented itself through a series of reassortments, producing a much more virulent and transmissible virus  which arrived in Europe last fall (see EID Journal: Reassorted HPAI H5N8 Clade 2.3.4.4. - Germany 2016).



Unlike our first two subtypes (H5N1 & H7N9), we've seen no evidence that H5N8/H5Nx has infected humans.   For now it primarily poses a threat to poultry producers and wild birds.

But, as the WHO recently warned, just because it hasn't infected humans - that doesn't mean it can't.

Providing some additional weight to that warning, recently in Sci Rpts: H5N8 - Rapid Acquisition of Virulence Markers After Serial Passage In Mice - we looked at laboratory experiments which seem to support the idea that H5N8 has the potential to adapt to mammalian hosts - including humans.

 


H5N6




The final entry in today's list is HPAI H5N6, which emerged at roughly the same time as H5N8 (early 2014) in both Laos and Southern China, and a few months later in Vietnam.  
Slower off the mark than H5N8 - at least in terms of geographic expansion - H5N6 this winter made its first big foray outside of China, causing major outbreaks in Korea, Japan, and in the past week, showing up in Taiwan. 
Like its clade 2.3.4.4 cousin H5N8, H5N6 is spreading remarkably well via migratory birds - and this year seems to be causing far more bird deaths in the wild.   The H5N6 virus - like all of the other entries in this list - continues to evolve. 

Unlike H5N8, H5N6 has a (limited) history of infecting - and killing - humans. So far, the only human infections we've seen have been in China, despite its spread in Korea, Japan, and Vietnam.  The last human case reported from China was in November of last year.



Why the virus has not infected humans outside of China remains unknown, although Korea and Japan - alert to the risks - are likely taking more precautions (PPEs, Antivirals, etc.) against infection. 


Epilogue


There are a number of other avian viruses of concern - including H9N2, H6N1, H10N8, and H7N7 - so one shouldn't think of this list as complete.  And we've a completely separate array of swine-origin viruses with some degree of pandemic potential to monitor as well (see Eurosurveillance: Swine Origin H1N1 Infection Leading To Severe Illness - Italy, 2016).
  
And, as we discussed recently in UK: DEFRA Cautions Pig Famers Over Avian Flu, swine viruses can reassort with avian viruses, opening up additional avenues for influenza evolution.

While none of this assures that a pandemic is in our immediate future, it is worth noting that we have more novel flu viruses in play (and interacting with other viruses) than ever before, with each taking uncounted rolls with their evolutionary dice.  

Their ability to mix-and-match gene segments, to adapt to new hosts via serial passage, and to spread farther and more efficiently via migratory birds makes them not only fascinating to watch, but a genuine public health threat of global concern.

1 comment:

Carol Owens said...

Michael:
I wanted to compliment you on your excellent article of "A New Avian Flu Review". Beverly was kind enough to send it to me and her other email friends. It's very well written and very well explained. Thank you so much for staying on top of the various fast changing flu viruses circulating now. Please continue to give us your analysis of the situation because it makes us feel better to know you have a complete understanding of it all and that you are willing to share your wisdom.
Carol Owens