JVI: The Emergence & Evolution Of H10 Avian Viruses In Chinese Poultry

 

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After nearly a decade during which time HPAI H5N1 virus pretty much ruled the bird flu roost, the past few years has seen the emergence of at least a half dozen new avian influenza subtypes, all of which appear to have originated when wild bird viruses reassorted in Chinese poultry.

 

Included in this rogue’s gallery are H7N9, H5N2, H5N3, H5N5, H5N6, H5N8, H7N7 and H10N8.

 

In a case of good timing  - just two weeks before China announced their first H7N9 outbreak - we saw a report published in the EID Journal: Predicting Hotspots for Influenza Virus Reassortment, that pegged Eastern China as one of the world’s most fertile regions for producing new flu subtypes (see also Viral Reassortants: Rocking The Cradle Of Influenza). 

 

We’ve seen numerous H5s, H7s, and H10s emerge out of China over the past few years, and almost all of them have a common denominator: 

 

While their HA and NA genes differ, their internal genes all carry contributions from the H9N2 avian virus.

 

H9N2 is considered a low path avian virus, and despite aggressive vaccination policies in China, it has become rife in Asian poultry.

 

Last month, in PNAS: Evolution Of H9N2 And It’s Effect On The Genesis Of H7N9, we looked at a study that found a new, better adapted genotype  (G57) of the H9N2 virus had emerged  – one that evades the poultry vaccines currently in use – and that it has become widespread among vaccinated Chinese poultry since 2010. 

 

Poorly matched flu vaccines can often inhibit symptoms without actually preventing infection.  As a result, subclinical infections go undetected - allowing drifted viruses to circulate unnoticed - and new variants or reassortants to emerge.

 

These failures are not unique to the H9N2 vaccines, as we’ve seen this process described recently with H5 vaccines as well (see EID Journal: Subclinical HPAI In Vaccinated Poultry – China & Egypt: A Paltry Poultry Vaccine). 

While the growing constellation of H5 viruses, along with H7N9, are currently viewed as our biggest avian flu threats, in late 2013 and early 2014 we saw three H10N8 infections in China (2 fatal), all linked to poultry exposure (see HK CHP Notified Of Fatal H10N8 Infection In Jiangxi).

Human infections with H10 viruses have only rarely been reported in the past, with H10N7 detected in two children in Egypt in 2004 (see Avian Influenza Virus A (H10N7) Circulating among Humans in Egypt) and among a handful of abattoir workers in Australia in 2012 (see EID Journal: Human Infection With H10N7 Avian Influenza).  

 

But unlike these recent H10N8 cases, their illnesses were described as mild, and of short duration.

A side note, we also looked at a recent outbreak of H10N7 in European seals (see Avian H10N7 Linked To Dead European Seals), with warnings to the public to avoid contact.

 

Suddenly H10 viruses were on our radar, and while it wasn’t immediately clear how much of a threat they posed (to the poultry industry, or to human health), scientists were eager to investigate.  A couple of recent examples include:

 

• In June of 2014, Eurosurveillance carried a report (see Genesis of the novel human-infecting influenza A(H10N8) virus and potential genetic diversity of the virus in poultry, China) that showed the H10N8 virus – like so many of the other emerging avian subtypes in China – carried the internal genes of the H9N2 virus.
• Last October, in BMC: H10N8 Antibodies In Animal Workers – Guangdong Province, China, we saw preliminary serological studies among poultry workers suggesting some exposures may have occurred prior to the first documented human case in 2013.

 

Yesterday the Journal of Virology published a paper, authored by some of the biggest names in avian flu research, that looks at the emergence, evolution, and spread of H10 avian influenza viruses in China.  Not only have they found the incursion of new H10N8 viruses into Chinese poultry, they’ve also found H10N6 variants as well.

 

While the full study is behind a pay wall, we have the following abstract.

 

Emergence and evolution of H10 subtype influenza viruses in poultry in China

Chi Ma, Tommy Tsan-Yuk Lam, Yujuan Chai, Jia Wang, Xiaohui Fan, Wenshan Hong, Yu Zhanga,, Lifeng Li, Yongmei Liu, David K. Smith, Richard J. Webby, Joseph S.M. Peiris, Huachen Zhua,* and Yi Guan*

ABSTRACT

The H10N8 human infection cases identified in late 2013 and early 2014 in Jiangxi, China have raised concerns over its origin, prevalence and development in this region. Our long term influenza surveillance in the past 12 years on poultry and migratory birds in southern China showed that H10 influenza viruses have been introduced from migratory to domestic ducks over several winter seasons at sentinel duck farms at Poyang Lake where domestic ducks share their water body with over-wintering migratory birds.

H10 viruses were never detected in terrestrial poultry in our survey areas until August 2013 when they were identified at live poultry markets in Jiangxi. Since then, we have isolated 124 H10N8 or H10N6 viruses from chickens at the local markets, revealing an ongoing outbreak.

Phylogenetic analysis of H10 and related viruses showed that the chicken H10N8 viruses were generated through multiple reassortments between H10 and N8 viruses from domestic ducks and the enzootic chicken H9N2 viruses. These chicken reassortant viruses were highly similar to the human isolate, indicating the market chickens were the source of the human infection.

Recently, the H10 viruses further reassorted, apparently with H5N6 viruses, and generated an H10N6 variant. The emergence and prevalence of H10 viruses in chickens and the occurrence of human infections provide direct evidence of the threat from the current influenza ecosystem in China.

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For now it isn’t at all clear how much of a threat H10N8, H10N6, or any other H10 subtype poses, but the fact that we continue to see this surge in new avian subtypes is a genuine concern.

 

Simply put, the greater the number of avian viruses in circulation, the more opportunities there will be for new subtypes, clades,and variant viruses to form.

 

And anytime you add complexity to a system, your chances of seeing an unwanted result go up.

SwAM: European Seal Deaths Continue From H10N7 Flu

Credit Wikipedia

 

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A couple of months ago in  Avian H10N7 Linked To Dead European Seals, I wrote about the recent die off of seals in Denmark and Germany and the determination that their deaths were the result of a combination of avian H10N7 influenza, pneumonia, and bacterial infection, which I followed up last month with a report in Eurosurveillance: Avian H10N7 Influenza In Harbor Seals.

 

In  2011 we saw a similar die off of seals in New England which was eventually linked to a different avian flu virus (see New England Seal Deaths Tied to H3N8 Flu Virus).

 

While we normally concentrate on novel avian and swine influenza strains,  the appearance and transmission of (avian-origin) influenza viruses in marine mammals raises concerns because they often show signs of mammalian adaptation – which may indicate a greater threat to humans down the road.

 

In 2012, in mBio: A Mammalian Adapted H3N8 In Seals, we saw  evidence that that particular avian virus had recently adapted to better bind to alpha 2,6 receptor cells, the type found in the human upper respiratory tract.

 

Although known human infections with avian H10N7 are limited, we’ve discussed them previously on several occasions . 

• In 2004, the first known human infections were reported among two Egyptian toddlers, as described in the  WHO/CDS/CSR/RMD report Avian Influenza Virus A (H10N7) Circulating among Humans in Egypt.
• And again, in 2012, in EID Journal: Human Infection With H10N7 Avian Influenza, we looked at a limited outbreak among workers with only mild symptoms at a chicken farm in Australia. 
• While not H10N7, we saw three severe infections with an H10N8 virus in China last winter.

 

Today we’ve a statement from the Swedish Agency for Marine and Water Management (SwAM) indicating that the number of dead seals – previously estimated at around 700 – is likely a huge undercount.   They estimate as many as 3,000 seal deaths likely due to H10N7.

 

 

More dead seals on the west coast than previously thought - Sea provides grants to increased sampling

Press Release • 2014-12-16 07:34 CET

Year to date, approximately 3000 harbor seals in Swedish and Danish waters died, probably infected by bird flu virus H10N7.

Marine and Water Authority, Sea, is now 245 000 SEK to the Museum of Natural History in order to get more samples of sick and dead seals.

In April this year, the first reports come in of sick and dead seals along the west coast, mainly in the Gothenburg archipelago. Researchers from the National Veterinary Institute and Museum of Natural History in Stockholm has taken samples of the dead seals. In October, scientists have estimated that it concerned a total of 700 dead animals in total, both in Sweden and Denmark, and that most likely died of bird flu virus H10N7.

- Today, researchers know that significantly more common seals died than those found washed ashore along the coast. Most people who become infected and died fell into the sea, it shows the results from the flyginveteringar made, says Susanne Folds, investigators at the CBD on the seas.

It is probably also the case that most seals infected but the majority have been able to form antibodies against the virus. Even in Germany has during the year found more sick and dead harbor seals than normal.

- Still, we have not the complete picture of how many seals affected, nor exactly how the infection has spread. We therefore spends money to enable researchers to continue sampling and mapping, says Susanne Folds.

Marine and Water Authority is responsible for managing gray and harbor seals and presented the autumn of 2012, management plans for these species. In 2014, it counted approximately 10 000 harbor seals in the Swedish västkusten-

So far this year, only West Coast hit by the seal death in Sweden and it is just about the harbor seal, we have not received reports of dead gray seal. Whoever finds dead seals should first contact the municipality where the find has been made and secondly Museum of Natural History.

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Avian H10N7 Linked To Dead European Seals

 

 

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In 2011 a die off of seals in New England made headlines, which was eventually linked to an avian flu virus (see New England Seal Deaths Tied to H3N8 Flu Virus).  While not a new revelation that seals were susceptible to influenza viruses, this did raise concerns as in 2012, in mBio: A Mammalian Adapted H3N8 In Seals, we saw the first hints that this virus had recently adapted to bind to alpha 2,6 receptor cells, the type found in the human upper respiratory tract.

 

Until it landed in seals, this H3N8 strain was an avian adapted virus. That is, that it bound preferentially to the kind of receptor cells commonly found in the digestive and respiratory tracts of birds; alpha 2,3 receptor cells.

 

Seals were suddenly on the radar as potential `mixing vessels’ for influenza, much in the same way as pigs have been for years.  The good news being that seals have less opportunities to mingle with humans than do pigs.

 

Additional research, published this past September (see Nature Communications: Respiratory Transmission of Avian H3N8 In Ferrets), confirmed that this `virus has an increased affinity for mammalian receptors, transmits via respiratory droplets in ferrets and replicates in human lung cells.’

In recent weeks there have been reports of large die offs of seals in Denmark and Germany (My thanks to Fred de Vries for the emailed head’s up), and this past week it was determined that a combination of avian H10N7 influenza, pneumonia, and bacterial infections were behind these deaths.

 

This report from the Technical University of Denmark.

 

Seals from several areas of Denmark were infected with influenza

Viral Zoonoses

National Veterinary Institute have found the influenza virus in seals from Anholt, fjord and three locations on the west coast. For the first time, identified a major flu outbreak among seals in Europe.

In recent months, we have found several dead seals along the Danish coasts than normal, and the National Veterinary Institute studies show that the cause of an outbreak of influenza.

In early July this year showed the National Veterinary Institute for the first time influenza type H10N7 two seals from Anholt. In September, the same virus was detected in dead seals from the fjord, and in October, the influenza virus has also been detected in dead seals at White Sands, Sædding and Skallingen on the west coast. The latter virus is not yet typed, but there are probably talking about the same H10N7 virus. The same virus is also detected in dead seals along the Swedish west coast.

"There are previously reported outbreaks of influenza in seals in Asia and the United States, but this is the first time that a major outbreak of influenza virus is found in seals in Europe," says Professor Lars Erik Larsen Section of Virology at the National Veterinary Institute.

Influenza virus weakens the seals, thus becoming more susceptible to other infections which may contribute to the deterioration of the disease and possibly lead to seal door.

"Initially, the seals probably got the flu by being in contact with birds or their droppings, but subsequently there has probably been no suggestion that the virus has infected from seal to seal," explains Lars Erik Larsen.

Do not touch the seals

Discovery of influenza virus in wild ducks are common, without giving rise to infection of other animals and humans. There are no reports of infection in people with the virus identified in these outbreaks among seals in Denmark, but other influenza viruses of the same type have previously caused light infection in humans.

"If you found dead seals should not touch them, but contact Naturstyrelses local wildlife consultant," says Special Mariann Chriél from the Section of Diagnostics and Emergency at the National Veterinary Institute.

 

Although known human infections with avian H10N7 are limited, we’ve discussed them on several occasions in the past.  In 2004, the first known human infections were reported among two Egyptian toddlers, as described in this report by WHO/CDS/CSR/RMD

 

Avian Influenza Virus A (H10N7) Circulating among Humans in Egypt

The National Influenza Center (NIC) in Egypt and the WHO Influenza Collaborating Centre in the UK reported the isolation of Avian Influenza A (H10N7) from two human specimens. They refer to two one-year-old infants, residents of Ismaillia, who recovered after presenting a fever and cough. The father of one of them is a poultry merchant who frequently traveled between Isamillia and Damietta. In the latter town, five cases of the same virus were isolated from wild ducks between 18 and 22 April 2004, from samples taken from a market of hunted migratory birds. Additional preliminary investigation tested negative in 75 human samples collected in Ismaillia and in 13 samples from migratory birds from the same market. No influenza outbreak has been reported among poultry in Egypt. At present, there are no public-health implications from this event.
 

And again, in 2012, in EID Journal: Human Infection With H10N7 Avian Influenza, we looked at a limited outbreak among workers at a chicken farm in Australia.  While their symptoms were mild and of short duration, the abattoir instituted enhanced PPE requirements for employees to try to prevent future infections.

 

Given its limited history of infecting humans, and the mild symptoms it has provoked, H10N7 seems an unlikely candidate to cause a serious public health threat. 

 

Of course, you could have said the same thing about avian H7 viruses two years ago.  All that changed when a new and deadly H7N9 emerged in China.

 

H10N7  – like all influenza A viruses –  has the ability to drift, mutate, or reassort with other influenza viruses and – over time -  continually re-invent itself.  

 

Which makes surveillance of events – such as this seal die off – an important part of the world’s efforts to detect the next emerging disease threat – and perhaps even stop it -  before it can pose a serious public health risk.

EID Journal: Human Infection With H10N7 Avian Influenza

 

 

 

 

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Although they are only rarely detected, there is evidence to suggest that humans may be infected by avian influenza viruses more often than is commonly suspected.

 

Every year billions of people around the world experience flu-like symptoms that can stem from any of hundreds of different viruses.

 

Of those, only the tiniest fraction are tested to see what pathogen caused the illness.

 

While most people are aware of the roughly six hundred H5N1 `bird flu’ infections detected over the past decade, we’ve also seen a smaller number of human infections caused by a variety of avian and swine origin flu viruses.

 

 

In 2003, an outbreak of H7N7 at a poultry farm in the Netherlands went on to infect at least 89 people (mostly mildly, but 1 death), and many more may have been infected subclinically.

 

In Egypt - in 2004 -  2 infants were shown to be infected by the H10N7 avian flu virus.

 

In 2006 1 person in the UK was confirmed to have contracted H7N3, and the following year, 4 people tested positive for H7N2 – both following local outbreaks in poultry.

 

But in terms of concern, the closest runner up to H5N1 virus right now is probably H9N2 – which is known to have infected a handful of humans, mostly in Asia.

 

 

During the last half of 2011 we also saw the emergence of a small number of H3N2v swine influenza infections (see H3N2v: Three’s A Crowd) in the United States.  

 

Over the years, we’ve seen a small number of sero-prevalence studies that have looked for (and found) evidence of prior infection by avian influenzas in people exposed to poultry or wild birds, including this one from 2006.

 

Avian Influenza among Waterfowl Hunters and Wildlife Professionals

James S. Gill,* Richard Webby,† Mary J.R. Gilchrist,* and Gregory C. Gray‡

ABSTRACT

We report serologic evidence of avian influenza infection in 1 duck hunter and 2 wildlife professionals with extensive histories of wild waterfowl and game bird exposure. Two laboratory methods showed evidence of past infection with influenza A/H11N9, a less common virus strain in wild ducks, in these 3 persons.

 

 

Interestingly, antibodies to the relatively rare H11N9 virus were detected in these 3 individuals, while antibodies for the far more common H4 and H6 avian viruses (known to circulate in American ducks) were not.

 

One theory that has been suggested is that humans are less likely to develop long-lasting antibodies when exposed to avian-type influenza viruses. 

 

Which brings us to a new study that appears in the May edition of the CDC’s EID Journal that detected the H10N7 avian influenza virus in two poultry abattoir workers in Australia.

 

 

Influenza Virus A (H10N7) in Chickens and Poultry Abattoir Workers, Australia

Article Contents

George G. Arzey , Peter D. Kirkland, K. Edla Arzey , Melinda Frost, Patrick Maywood, Stephen Conaty, Aeron C. Hurt, Yi-Mo Deng, Pina Iannello, Ian Barr, Dominic E. Dwyer, Mala Ratnamohan, Kenneth McPhie, and Paul Selleck

Abstract

In March 2010, an outbreak of low pathogenicity avian influenza A (H10N7) occurred on a chicken farm in Australia. After processing clinically normal birds from the farm, 7 abattoir workers reported conjunctivitis and minor upper respiratory tract symptoms. Influenza virus A subtype H10 infection was detected in 2 workers.

 

 

Although 7 abattoir workers reported symptoms, only 2 tested positive for the H10 virus. The authors write:

 

The conjunctivitis and other reported symptoms among the 7 workers were mild and of short duration, and there was no evidence of seroconversion by hemagglutination inhibition or virus neutralization tests in any of the workers from whom convalescent-phase blood was collected, including the 2 with confirmed influenza A subtype H10 infection.

 

These findings are consistent with the mild symptoms and lack of serologic evidence reported in humans after experimental infection with influenza A (H10N7), which may indicate the limited ability of the virus to multiply and stimulate a detectable immune response in humans (10).

 

Other studies have reported no evidence of elevated subtype H10–specific antibody titers among poultry abattoir workers, although serologic evidence of subtype H10 infection was detected among turkey farmers in the absence of clinical symptoms (11).

 

Although this outbreak was limited, and the symptoms were mild, the abattoir has instituted new policies requiring PPEs (personal protective equipment) for employees who have direct exposure to birds and carcasses.

 

Admittedly, the H10N7 virus would seem an unlikely public health threat.

 

But this study does show that it can infect humans, and that mild or subclinical infections from avian viruses are probably happening that are not being picked up by routine surveillance.

 

When it comes to the next influenza threat, we worry most about H5N1 and H9N2. But the next pandemic virus to successfully jump species could just as easily come out of left field, as we saw in 2009 with the H1N1 swine flu.

 

 

All of which highlights the importance of establishing better global surveillance of humans, and farm animals, for the next emerging influenza virus.

 

Regardless of its strain.