Understanding the ecology, epidemiology and evolution of the 2017 outbreak of highly-pathogenic H5N8 avian influenza virus in a wild mute swans

Lead Research Organisation: University of Oxford
Department Name: Zoology

Abstract

Highly pathogenic avian influenza (HPAI) viruses cause substantial economic losses to the poultry industry, and pose a significant threat to animal and human health. HPAI first came to prominence in the late 1990s with the emergence from Asia of the H5N1 lineage, which resulted in the culling of 100s of millions of birds and more than 500 human deaths. HPAI resurfaced as a global threat in 2013, with the emergence in China of a novel strain belonging to subtype H5N8.

The speed of global H5N8 spread since 2014 has surprised scientists. The strain spread rapidly through Asia, North America, Europe, and most recently, Africa. The spread to North America is unprecedented, at an estimated cost of ~$3.3 billion to businesses there. A report published last October concluded that H5N8 global spread was driven primarily by long-distance bird migration.

Reports of H5N8 outbreaks in both wild and farmed birds across Europe increased in autumn 2016, spreading westwards until they reached the UK in late December. Cases in wild birds have been reported in Wales, Scotland and England. The largest outbreak to date is ongoing within a large population (~750) of wild mute swans in Abbotsbury, on the Dorset coast in southern England. Although only 9 swans (so far) have laboratory confirmed H5N8 infections, more than 175 untested swans have died since the start of the outbreak, vastly in excess of normal mortality. The first H5N8 infection was detected in a dead swan found at the Swannery on 23rd December 2016. Although mortality appears to have decreased from the apparent peak in the second week of January 2017, an above-normal number of dead birds are still being recovered and the outbreak is still considered to be current and ongoing by the authorities (2nd February 2017).

This outbreak, whilst devastating for the bird population, could tell us much about how HPAI spreads in wild birds. The long-lived swans have been subjected to long-term ecological study by ornithologists at the University of Oxford and are individually ringed; for most birds we know age, sex, parentage and other variables. Crucially, exactly the same population suffered an outbreak of H5N1 HPAI in early 2008. However, in 2008 only 10 swans died, almost all of which were <3 years old. Our research after the 2008 outbreak showed that older birds were more likely to have antibody responses that might help give immunological protection against avian influenza. Specifically almost all birds >3 years old harbour influenza antibodies and older birds have antibodies to a broader range of different influenza strains. Thus we hypothesise that previous exposure to common, mild forms of influenza may have protected these wild birds against H5N1 infection.

The current outbreak offers the potential to directly compare H5N1 and H5N8 HPAI epidemiology in the same population of wild birds, an opportunity that we think is unique worldwide. High bird mortality during H5N8 outbreaks have been reported elsewhere in Europe, and by comparing the ecology and epidemiology of the H5N8 and H5N1 outbreaks at Abbotsbury we may be able to find out the cause of this.

We aim to find out how, and from where, the H5N8 virus entered the population, how long it was present locally before it was detected, and how the virus spread through the population. To do this we will sequence the genomes of the viruses recovered from affected birds, and analyse these genomes using established statistical methods. We will look at the antibodies that birds in the population carry, to see if some birds, particularly the older ones, are protected against severe disease as a result of previous exposure to harmless strains of avian influenza. This will help us understand if immunity to flu in humans and long-lived birds is similar or different, and extend our understanding of how this virus spreads in wild birds.

Planned Impact

This project has particularly direct and well defined impacts for several non-academic institutions and entities.

(1) The proposed research will be of great relevance to those responsible for detecting and controlling avian influenza outbreak in wild birds and farmed poultry, specifically the APHA (Animal & Plant Health Agency). New H5N8 outbreaks are continuing to be detected in England. The UK government will therefore benefit substantially from a detailed understanding of how H5N8 spreads in wild bird populations.The APHA is directly represented here through project partner Prof Ian H Brown, who is Head of Virology at APHA-Weybridge and the Director of the EU/OIE/FAO International Reference Lab for Avian Influenza. Prof Brown sits on numerous national and international committees (listed below); Prof Brown will guide the dissemination of our results to these groups, either by providing evidence directly himself, or by inviting us to submit evidence.
- OFFLU avian influenza expert group
- WHO/OFFLU H5N1 Evolution Working Group
- EU disease emergency task force
- GOARN focal point for APHA, UK, and member institution in the European Virus Archive (EVA) Network
- Centres of Excellence on Influenza Research and Surveillance (CEIRS) (Scientific Committee)
- Global Initiative on Sharing Avian Influenza Data (GISAID) (Scientific Advisory Council)
- UK New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG)
- UK NFU Health Committee
- UK Joint Board for Emerging Infections and Zoonosis
- UK Poultry Health and Welfare Group
- UK Poultry Disease Group
- UK Outbreak Readiness Board

(2) The Abbotsbury Swannery is a tourist destination owned and managed by the Ilchester Estates. Our research could lead to insights that will benefit the health of the birds at Abbotsbury or reduce the likelihood of future HPAI outbreak at the site. Our findings will be communicated directly to the lead swanherd, Dave Wheeler, with whom we are in frequent contact.

(3) The broader relevance of our results for food security can be communicated through the activities of the Oxford Martin Programme on the Future of Food (http://www.futureoffood.ox.ac.uk). Advice on dissemination to the wider food system will be sought from Prof Lord John Krebs, who is Chair of the advisory group of the Future of Food programme.

(4) Understanding the potential for spillover of H5N8 into farmed poultry is also of great scientific and economic interest to the UK poultry industry.

Publications

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Hill SC (2019) Comparative micro-epidemiology of pathogenic avian influenza virus outbreaks in a wild bird population. in Philosophical transactions of the Royal Society of London. Series B, Biological sciences

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Sarah C Hill (2019) Comparative micro-epidemiology of pathogenic avian influenza virus outbreaks in a wild bird population in Philosophical Transactions of the Royal Society B

 
Description (1) We have analysed data from the 2017 H5N8 outbreak. We discovered a higher mortality rate in hatch-year birds than in any other age cohort. We have quantified the time course of the outbreak, leading to an estimate of the basic reproductive number of the epidemic (R0). (2) We have quantified mortality at the population level and shown it was significantly greater than non-outbreak years. Importantly, the mortality rate of the H5N8 outbreak was significantly higher than that observed during the previous H5N1 outbreak in the same population. That said, the age-distribution of mortality is similar for the two outbreaks. (3) We have generated 12 complete or nearly complete viral genomes from infected birds affected during the 2017 H5N8 outbreak. Final validation of these genomes is underway. Initial analyses of these genomes revealed the date of entry of the H5N8 virus into the study population (Nov 2017). The estimated season of introduction was very similar for both the H5N1 and H5N8 outbreaks, suggesting a consistent source or route of introduction for pathogen avian influenza viruses in the population. Further analyses of these genomes is ongoing. (4) We obtained blood samples from healthy swans sampled during summer 2017 (under Home Office licence number P516CDFB6). Serological analyses of these samples is ongoing.

Update Feb 2019: All research is complete and all objectives have been met. We further detected the presence of a strong age-structure in morbidity that likely arises from an equivalent age-structure in immunological responses, quantified by population level serology. The predictability of the epidemic features across multiple outbreaks in a complex natural population is striking, and contributes to our understanding of HPAIV in wild birds.
Exploitation Route We will complete our research and publish our findings in a scientific paper and at international conferences. Conference Abstracts have already been submitted and accepted. Note: although the start date of this grant is April 2017 the named PDRA was employed on the grant from Nov 2017 to Mar 2018 (5 months, one month later than planned in the proposal). Field sampling was between June and November 2017, as planned in the proposal. Therefore serological analyses of the samples that were collected are still ongoing. We have already shared our provisional results with the Animal & Plant Health agency, and our findings helped to inform their response to the subsequent H5N6 outbreak in Jan 2018. Further, we have started to collaborate with the Royal Veterinary College regarding the use of MinION virus genome sequencing in developing countries, and this collaboration has led to a GCRF hub grant proposal that has been invited to the full submission stage. Lastly, we continue to collaborate and share findings with the "Global Consortium for H5N8 and related avian influenza viruses" coordinated by Prof Mark Woodhouse.

Update Feb 2019: We continue to discuss and explore opportunities for avian influenza surveillance in the UK with the Animal & Plant Health agency.
Sectors Agriculture, Food and Drink,Environment

 
Description This urgency project was created in response to, and to scientifically evaluate, the outbreak of highly pathogenic H5N8 avian influenza at our study site in Jan 2017. However, during the timeframe of this project, a new highly pathogenic avian influenza outbreak (of the H5N6 subtype) occurred at our study site, in Jan 2018. Control of this outbreak was undertaken by our colleagues at the Animal and Plant Health Agency (APHA). The results we had already obtained from our study of the H5N8 outbreak helped to inform APHA's outbreak control efforts. Our findings also guided their sampling and surveillance strategies during the outbreak. In addition we gave our analytic and field support to the APHA team. Details of the APHA's work can be found at https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/678944/avian-flu-wild-birds-H5N6-180130.pdf. We continue to collaborate with the APHA and we wish to undertake further analysis of the new outbreak that occurred in 2018. We asked for extra support from NERC to do this, but unfortunately it was decided that extra funding is not possible in the context of an Urgency Grant.
First Year Of Impact 2018
Sector Agriculture, Food and Drink,Environment
Impact Types Policy & public services

 
Title Influenza virus genome sequences 
Description Avian influenza gene and genome sequences generated as part of this project are available from GenBank (H5N8 sequences, accession numbers MH819084-MH819175) or GISAID (H5N6 sequences, GISAID identifiers EPI ISL 292223 - 292225). 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
Impact These genomes are published in the following paper: Sarah C Hill et al. (2019) Comparative micro-epidemiology of pathogenic avian influenza virus outbreaks in a wild bird population. Phil Trans Roy Soc B. In press 
URL https://www.ncbi.nlm.nih.gov/genbank/
 
Title Population level sample collection 
Description Stratified collection of blood samples from individually identified wild birds of known ages suitable for serological analysis (ELISA and HI assays). 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? No  
Impact Not applicable - analysis and testing current underway and not yet complete. 
 
Description Biannual Fleet Study Group Meeting presentation 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact Presentation on avian flu outbreaks to staff at Abbotsbury Swannery, local landowners, and other local stakeholders
Year(s) Of Engagement Activity 2018
 
Description International conference talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Conference talk by Sarah Hill "Understanding the ecology, epidemiology and evolution of the 2017 outbreak of highly-pathogenic H5N8 avian influenza virus in wild mute swans" at "10th International Symposium on Avian Influenza". Follow up meeting during conference with UK Animal & Plant Health Agency representatives.
Year(s) Of Engagement Activity 2018
URL https://science.vla.gov.uk/flu-lab-net/isai2018/index.html
 
Description International conference talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Conference talk by Oliver Pybus "The ecology & genomic epidemiology of highly-pathogenic avian influenza viruses in Europe & Asia" at "Influenza 2017 Conference". Follow up meeting during conference with UK Animal & Plant Health Agency representative.
Year(s) Of Engagement Activity 2017
URL http://lpmhealthcare.com/influenza-2017/
 
Description Keynote talk at international conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Keynote lecture at the 15th Avian Immunology Research Group Conference, Sep 2018, Oxford, UK, titled "The ecology & epidemiology of avian influenza and other viruses in a wild bird population"
Year(s) Of Engagement Activity 2018
URL http://airg.zoo.ox.ac.uk
 
Description Meeting with APHA 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact In July 2018 we held a small one-day meeting with our collaborators from the Animal and Plant Health Agency to review the results of this project and to scope future strategies for the surveillance and prediction of pathogenic avian influenza in the UK.
Year(s) Of Engagement Activity 2018
 
Description Talk at international conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Research talk at Microbiology Society Annual Conference, April 2018. Birmingham, UK, titled "The genomic ecology and epidemiology of avian influenza and other viruses in natural populations"
Year(s) Of Engagement Activity 2018
URL https://microbiologysociety.org/event/annual-conference/annual-conference-2018.html