OIE/FAO Notifications Of Bird Flu In Italy & Romania

A busy avian flu season for Europe (prior to Mar. 13th)  – Credit Defra

 

 

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On Friday, in Media Reports: Bird Flu Detected In Romania & Italy, we looked at two  reported bird flu outbreaks in Europe. The Romanian outbreak – reportedly H5N1 – came on the heels of a similar announcement earlier last week from neighboring Bulgaria.

 

The outbreak in Italy wasn’t immediately identified, but it follows earlier outbreaks of LPAI H7, LPAI H5, and HPAI H5N8 viruses.

 

Today we’ve confirmation of both of these outbreaks, and of their subtypes, from separate reports issued by the OIE and the FAO.

 

First stop, Italy – where low path (LPAI) H7N1 has been identified on a farm in the Veneto region in the following FAO report.

 

 

Of greater concern is an outbreak of HPAI H5N1 in waterfowl around the Danube Delta, as described in the following OIE Report, which describes 64 dead pelicans. 

 

 

Source of the outbreak(s) or origin of infection

• Unknown or inconclusive

Epidemiological comments

On 25 March, the County Sanitary Veterinary and Food Safety Directorate (CSVFSD) of Tulcea was notified by the Danube Delta Biosphere Reserve Administration (ARBDD) about the identification of 64 carcasses of pelicans in an inhabited area, on Ceaplace island, Sinoe lake. This area is located at the border of Tulcea and Constanta Counties, and no other localities with domestic birds are found on a radius more than 10 km. The entire population of pelicans counted initially more than 250 birds, adults and young. Excluding the dead pelicans (found in different stages of putrefaction), no other birds were observed with clinical signs in the area. Also, in the area were observed other birds species, still unspecified.

 

 

After several years of relative quiescence on the bird flu front (at least, outside of China), we are suddenly seeing a remarkable surge in activity, involving several different strains.  

H5N1 is not only on the move in migratory birds – showing up in Eastern Europe, and Nigeria after five years absence – it is also raging in poultry in Egypt, and is spilling over into humans this winter at a record rate (see FAO: Egypt’s H5N1 Case Count Continues To Climb).

 

Meanwhile, the recently emerged H5N8 virus has not only spread across much of Eastern Asia, and into both Europe and North America, it has spawned a number of `local’ reassortant viruses. `New’ versions of H5N2, H5N3, and H5N1 have appeared in Taiwan, and in North America, and already they have had major impacts on the poultry industry in both regions. 

 

And while far less worrisome for now, we’ve also seen an unusual number of low path (LPAI) outbreaks (H5s & H7s) in poultry from Italy, to the UK, to Kansas.   

 

In many ways, the winter of 2014-15 has seen more bird flu activity – over a greater geographic range – than we’ve seen since the great bird flu expansion of 2006, when H5N1 escaped the confines of Asia and barnstormed much of  Europe (see H5N8: A Case Of Deja Flu?).

 

All of which has brought, once again, the role of migratory and wild birds in the spread of these viruses back to the forefront.  

 

While there are still a lot of missing pieces to this puzzle – and outbreaks often appear linked to or exacerbated by the movement of poultry products (legal and illicit), equipment, or personnel – this resurgence in bird flu has brought wild and migratory birds under new scrutiny.  

 

A few recent blogs on the topic include:

 

Erasmus Study On Role Of Migratory Birds In Spread Of Avian Flu

FAO On The Potential Threat Of HPAI Spread Via Migratory Birds

The North Atlantic Flyway Revisited

Study: Airborne Transmission Of H7N1 in Ferrets After Serial Passage

Classic serial passage study, albeit with ducks instead of ferrets

 

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When novel flu viruses jump species, they rarely do so fully adapted to the new host. There is generally period of transition – which may be measured in days, weeks, years . . . or even decades -  before the virus can adapt to the new host species.

 

Sometimes the gulf between the original host and the new species is too great, and this adaptation never takes place.

 

Even though we don’t fully understand how it works, the concept is fairly simple.

 

When a flu virus infects a cell, it immediately sets upon making thousands of copies of itself.  But single-stranded RNA flu viruses are notoriously sloppy replicators, and some of these copies will invariably carry small transcription errors.   Most of these `variants’  will prove either neutral or detrimental to the survival and propagation of the virus, but occasionally a change will occur increases its biological fitness in the new host.

 

Those, as you might expect, are the ones that thrive and perpetuate themselves. 

 

Which is why we are always concerned whenever a novel flu virus jumps to humans, as each instance is another opportunity for the virus to `figure us out’.

 

One of the classic lab experiments used to `hurry’  this evolutionary process along is called a serial passage experiment (see graphic at top of this post), where an test subject (usually a mouse or ferret) is infected with a virus, and that virus is then collected and used to inoculate another test subject.  This process is repeated a number of times.

 

After 10 or so iterations, the virus is then examined for `adaptive changes’ and/or changes in behavior (ie. virulence, transmissibility).  Sometimes, after multiple passes through a series of hosts, the virus picks up mutations that favor its survival in the new species. 

 

This is essentially how Ron Fouchier created a `mammalian-adapted’ H5N1 virus in the laboratory in 2011, and it mimics what viruses do in the wild, albeit at an artificially enhanced speed.

 

For a flu virus to spark a pandemic, it basically needs to meet three criteria:

 

1. It needs to be able to infect humans
2. It needs to be pathogenic in humans (causes disease)
3. It needs to be efficiently transmitted from human-to-human

 

The avian influenza viruses we’ve been watching (H5N1, H7N9, H9N2, H7N7,  etc) all appear to meet the first two criteria (although severity of disease varies greatly between subtypes), but so far item #3 remains absent.

 

The primarily barrier to a pandemic appears to be a lack of `airborne transmission’  between humans.

 

Since ferrets are highly susceptible to influenza, and exhibit a similar respiratory response to infection to humans (coughing & sneezing), they are often used for transmissibility studies. 

 

Infected ferrets are placed in cages adjacent to healthy ferrets, but any direct contact is prevented.  If the healthy ferrets catch the virus, its a pretty good indication of airborne transmission.

 

Today, we’ve a study appearing in the Journal of Virology that takes the avian H7N1 virus – passes it serially through ferrets 10 times  – and then tests the virus for both transmissibility and virulence.  The end result was an H7N1 virus that was transmissible via the airborne route (in ferrets) with no apparent loss of virulence.

 

 

Airborne Transmission of Highly Pathogenic H7N1 Influenza in Ferrets

Troy C. Sutton1, Courtney Finch, Hongxia Shao, Matthew Angel, Hongjun Chen, Ilaria Capua, Giovanni Cattoli, Isabella Monne and Daniel R. Perez

Avian H7 influenza viruses are recognized as potential pandemic viruses as personnel often become infected during poultry outbreaks. H7 infections in humans typically cause mild conjunctivitis; however, the H7N9 outbreak in the spring of 2013 has resulted in severe respiratory disease. To date, no H7 viruses have acquired the ability for sustained transmission in humans.

Airborne transmission is considered a requirement for the emergence of pandemic influenza, and advanced knowledge of the molecular changes or signature required for transmission would allow early identification of pandemic vaccine seed stocks, screening and stockpiling of antiviral compounds, and focused eradication efforts on flocks harboring threatening viruses.

Thus, we sought to determine if a highly pathogenic influenza A H7N1 (A/H7N1) vrus, with no previous history of human infection, could become airborne transmissible in ferrets.

We show that after 10 serial passages, A/H7N1 developed the ability to transmit to co-housed and airborne contact ferrets. Four amino acid mutations (PB2 T81I, NP V284M, M1 R95K, and Q211K) in the internal genes and a minimal amino acid mutation (K/R313R) in the stalk region of the HA protein were associated with airborne transmission. Furthermore, transmission was not associated with a loss of virulence.

These findings highlight the importance of the internal genes in host adaptation and suggest that natural isolates carrying these mutations be further evaluated. Our results demonstrate that a highly pathogenic avian H7 virus can become airborne transmissible in a mammalian host, and support on-going surveillance and pandemic H7 vaccine development.

Importance: The major findings of this report are that a highly pathogenic strain of H7N1 avian influenza can be adapted to become airborne transmissible in mammals without mutations altering the receptor specificity. Changes in receptor specificity have been shown to play a role in the ability of avian influenza viruses to cross the species barrier and these changes are assumed to be essential. The work herein challenges this paradigm, at least for the influenza viruses of the H7 subtype, which have recently become the focus of major attention as they have crossed to humans.

 

 

A bit surprisingly, four of the five amino acid changes that were associated with airborne transmission were found to occur in the internal genes (PB2, NP, M1) of the virus. Given the history of H9N2 donating its internal genes to novel reassortants (see Study: Sequence & Phylogenetic Analysis Of Emerging H9N2 influenza Viruses In China), these findings may help identify potential surveillance targets in that subtype, and others. 

 

This isn’t the first time we’ve seen evidence of airborne transmission of an H7 virus in ferrets.

 

In 2013, in Nature: Limited Airborne Transmission Of H7N9 Between Ferrets & Science: H7N9 Transmissibility Study In Ferrets), we saw lab experiments that showed this H7 avian flu virus could be transmitted between ferrets (albeit at low levels) via respiratory droplets.

 

So far, while airborne transmission has been demonstrated (in ferrets) in the lab, we’ve yet to see evidence of sustained and efficient airborne transmission of these novel avian viruses in humans.

 

But nature’s lab is open 24/7, new reassortant flu viruses are appearing all the time, and just because it hasn’t happened yet doesn’t mean it can’t happen sometime in the future.