Wednesday, November 10, 2021

DEFRA: Rapid Risk Assessment on Incursion of H5Nx HPAI



As I mentioned in my last blog, HPAI (Highly Pathogenic Avian Influenza) is threatening not only Europe, but Asia as well.  Today the UK's DEFRA has released a detailed Rapid Risk Analysis on this year's incursion of HPAI into Great Britain, and the rest of Europe.  

This 28-page report addresses not only the outbreaks since last May, but also observed changes in the H5Nx viruses that have been collected, and considers a number of specific areas of risk.  Interested parties will want to download, and review the document in its entirety. 

Although some of the amino acid changes that can enhance (or diminish) the zoonotic threat of HPAI H5 have been identified, how multiple mutations work in concert is far less well understood.  

You'll see a section (Hazard identification) which lists numerous mutations detected in a recent H5N1 sample, but exactly what they mean in terms of transmissibility, virulence, or increased threat to humans is far from clear. 

Last year, after a lull of 3 years, Europe saw a record setting avian epizootic. Based on the early arrival, and widespread detections of HPAI across Europe this fall, the study cautions:

This pattern of geographical distribution (see map above) follows a similar pattern of transmission in wild birds and spill-over into domestic poultry as observed for the epizootic of H5N1 HPAI in 2005-2008 in Europe, and in H5N8 HPAI in 2016-2017 and then 2020/21 in Europe. In those years, spread occurred along a similar route of migratory wild waterfowl causing wild bird die-offs in North and Central Europe.

It can be expected that the current H5Nx HPAI epizootic will continue to cause issues with the poultry sector for several months to come, if not for many months, if the virus continues to circulate in migratory and then in non-migratory waterfowl in Europe. 

A few excerpts from a much longer report follow:

Rapid risk assessment on incursion of H5Nx HPAI into housed or not housed poultryflocks and captive birds 

November 2021 


1. There is a heightened risk of an incursion of avian influenza H5Nx to the UK. This is evidenced by the wild bird cases occurring across Northern, Eastern and Central Europe and outbreaks in poultry in Netherlands, Italy, Czechia, Finland and Germany. In early October 2021 the risk of wild bird incursion was increased to MEDIUM. 

2. Since then, the report of HPAI H5N1 in a wild bird rescue centre in Worcestershire (AIV 2021/07) and a game bird establishment in Wrexham (AIV 2021/08) on 26 October and 1 November resp. and five other wild bird reports from areas of Southport, Preston, Fife, Edinburgh and Wrexham are the first confirmed events of HPAI H5N1 in GB since July 2021. Therefore, the risk level was increased to HIGH for wild birds on the 29 October 2021 with low to medium for exposure to poultry, depending on biosecurity. 

3. There has been a pattern of spread consistent with previous disease epidemics in which wild bird transmission was a factor. There is good evidence that spread to the UK by migrating wild waterfowl has happened in the past. 

4. There are a number of risk pathways for the introduction of disease to kept birds, and contact, whether direct or indirect, with infected wild birds is the most important one, especially with respect to a primary introduction to domestic birds. Secondary spread in the UK with our disease control measures and keeper awareness is a rare event; only one proven event of secondary spread has occurred, and that was in 2007, where spread between two units of the same business occurred through shared workers. 

5. Housing free range poultry could reduce the likelihood of infection incursion, from reducing the direct contact with wild waterfowl or with their contaminated environment. An EFSA analysis following the 2016/2017 epidemic concluded that housing birds gave a two-fold reduction in risk. 

6. However, to be effective, housing must be accompanied by thorough biosecurity measures to prevent the disease from being introduced to the poultry by contaminated people or other things that are taken into or enter the housing. EFSA concluded that stringent biosecurity measures, which include housing, bring a 44-fold reduction in risk. 

7. Under some circumstances, poultry will not be able to be housed, whether for practical or welfare reasons relating to their husbandry needs, and so housing will not be universally achieved.

8. Comparing the last two seasons when poultry cases were reported in the UK (2016/17 and 2020/21) a housing order was in place but only after 14 December 2020 before which there were seven commercial outbreaks in 2020/21 but none in 2016/17, when the housing requirement was put in place on 12 December 2016. However, the difference in the number of cases is probably related to the wider geographic area, infection pressure, earlier start and longer duration of the outbreak in 2020/21. 

9. The geographical extent of any housing requirement can be determined on the basis of proximity to large aggregates of wild waterfowl over the coming weeks as well as on the basis of practicality/feasibility and sustainability. It is not possible to say at this stage whether the infection pressure will increase over the coming weeks, whether the season will last for as long as it did in 2020/21 and what the geographic extent will be. Nevertheless, given the early start and wild bird cases already detected, this does appear to be a long season approaching. 

10.Any legal requirement to house and take biosecurity measures should be kept under review and adapted as needed to reflect emerging evidence, including levels of compliance with housing and biosecurity measures and the disease picture across Europe.


Hazard identification

 The hazard identified is the avian influenza virus, HPAI H5Nx subtype. Although the HPAI H5N1 virus has been isolated from the UK during the current season it is possible other strains will be detected in the coming months. HPAI H5N8 has been detected in Estonia, Finland, France and Sweden in the last few weeks. The OIE/WHO RL (Weybridge) has undertaken some preliminary sequence analysis of the GB virus. The virus maps across the whole genome with the H5N8 viruses (reported by the lab as part of an international collaboration) found in the Netherlands, Iraq, Russian Federation and Kazakhstan during the last 4 months (and therefore distinct from the strain that caused widespread outbreaks in the EU in the first part of this year).  

Weybridge analysed the available full genome sequence data of a H5N1 HPAIV obtained from a UK avian influenza disease investigation (A/chicken/England/053052/2021 and A/mute swan/England/053070/2021) and compared them with the CDC (Atlanta) H5N1 genetic changes inventory and Suttie et al. 2019 to identify genetic mutations that determine viral phenotypic characteristics of importance that may increase virulence, signal adaptation to mammalian species or alter susceptibility to existing antivirals. This totals 240 mutations or combinations of mutations. 

They observed 39 mutations/combinations of mutations. It should be noted that all of these genetic changes identified were also present in a representative UK H5N1 from 2020 (A/chicken/England/043315/2020) as well as H5N1 sequences provided from the Czechia (A/goose/Czech Republic/1850-1/2021 and A/duck/Czech Republic/1850-2/2021) and Russia (A/goose/Chelyabinsk/1341-3/2021 and A/Common Teal/Chelyabinsk1379- 1/2021). However, in addition to the mutations reported, one or both of the sequences from Russia contained additional substitutions in the PA (Q400P) and NP (I41V) proteins. These mutations are not expected to substantially alter the tropism of these viruses. 

• For the proteins of the polymerase complex, thirteen, two and four mutations/combination of mutations were identified in PB2, PB1 and PA, respectively. The majority of these genetic changes are reported to increase polymerase activity and virulence in mammals and chickens, but there were also mutations reported to decrease virulence in mice. However, important markers of zoonotic risk, PB2 E627K and D701N substitutions were not identified. 

Unlike European H5N8 and H5N5 HPAIVs from 2020, these H5N1 sequences, as with those from elsewhere in Europe across 2020/2021, contain a full-length PB1-F2 protein; an accessory protein with multiple functions including apoptosis and modulation of host immune responses and demonstrated to be a virulence factor in mammalian models. However, UK H5N8 HPAIVs from 2014 and 2016/2017 also had a full-length PB1-F2 protein, and these were not associated with increased risk of human infections. One substitution was also identified in this protein, which has been associated with enhanced virulence in mice. However, this substitution was also present in the aforementioned UK H5N8 sequence from 2014-2017 and is not thought to contribute to increased risk of mammalian tropism.  

The eight mutations identified in the HA protein are reported to increase binding to mammalian α2-6 receptors, with the T156A mutation being the only change that has also been observed in the Asian H5N6 viruses. However, the T156A mutation was also present in previous European H5Nx viruses. Nevertheless, all eight HA mutations are not considered characteristic of enabling the binding to α2-6 receptors in the literature. Therefore, it is predicted that the HA of these H5N1 viruses, will bind to avian α2-3 receptors, as with European H5Nx viruses circulating in 2020/2021. 

The two mutations identified in NP are associated with increased virulence in chickens and do not have any reported impact on mammalian adaptation. 

• Mutations in NA reported to affect zanamivir and oseltamivir susceptibility were not found

Within M1, three mutations associated with increased virulence in mice, chickens and ducks were identified. However, no mutations reported to effect amantadine and rimantadine susceptibility in M2 were identified. 

There is a lack of a deletion in NS1 at amino acid positions 80-84 that is conserved among contemporary H5 viruses, possibly decreasing the zoonotic potential of the H5N1 viruses in question. However, five mutations reported to increase virulence and decrease antiviral responses in mammals and chickens were identified.

In conclusion, whilst there are notable differences to contemporary H5Nx viruses, the UK H5N1 virus demonstrates no strong correlates for specific increased affinity for humans.


Assumptions and Uncertainties 

The wild bird counts for this year are not known and we are using an annual assessment based on previous years

• Other wild waterfowl species (although this assessment considers the most abundant) may also be important for the transmission of this virus. 

• The patterns of movement of gulls are more complex than waterfowl. They prefer to roost around land tips and reservoirs therefore these should not be ignored as potential sites of concern for proximity to poultry farms. 

• The evidence for the economic benefits and dis-benefits of housing birds is not part of this assessment.

 • The 2016/2017 epidemic allowed experts to analyse the likely risk factors leading to an incursion of avian influenza and while housing birds was assessed as giving a two fold reduction, other factors such as preventing access to wild birds (three fold) and improving biosecurity (four fold) are also significant. 

• Comparing 2016/17 to 2020/21, the higher number of cases observed in 2020/21 was probably related to the increased infection pressure starting earlier in the season. 

• While housing may prevent direct contact with wild waterfowl, it could increase indirect contact with contaminated environment and the birds may be under stress, leading to more disease transmission and greater likelihood of viral mutation. Regular contact with wild birds and their LPAI viruses may produce an environmental “vaccine” protection against HPAI 

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