Research and analysis

Investigation into the risk to human health of avian influenza (influenza A H5N1) in England: technical briefing 2

Updated 14 July 2023

Applies to England

The UK Health Security Agency (UKHSA) is working with the Animal and Plant Health Agency (APHA), the Department for Environment, Food and Rural Affairs (Defra) and the public health agencies of the 4 nations to investigate the risk to human health of avian influenza (influenza A H5N1) in England. This briefing is produced to share data useful to other public health investigators and academic partners undertaking related work. It includes early evidence and preliminary analyses which may be subject to change.

Data reported in the technical briefing is as of 14 February 2023 (or as specified in the text) to allow time for analysis.

Levels of human health risk related to the outbreak of avian influenza in England

These risk levels were developed by the Technical Group to help to establish triggers for enhancing assessment and response. The avian influenza outbreak can be considered to fall into one of 6 potential levels of transmission.

Level 0 (Baseline)

Avian influenza circulating in birds within normal bounds of prevalence and with normal epidemiological dynamics.

Level 1

Avian influenza circulating in birds with altered epidemiological dynamics and/or increased prevalence.

Level 2

Level 1 plus detection of spillover into mammals.

Level 3

Evidence of viral genomic changes that provide an advantage for mammalian infection.

Level 4

Sustained transmission in non-human mammalian species or any human detection and mutations in haemagglutinin (HA) which allow transmission. (A single human detection in a person exposed to infected birds, without HA mutations, does not raise the risk level to 4).

Level 5

Any human-to-human transmission.

The UK risk is currently assessed as at level 3.

Summary

Epidemiology in birds

Detections of A(H5N1) continue in wild and domestic poultry populations across England. In England, influenza A(H5N1) has been confirmed at 145 premises and in 656 wild birds from 413 locations in England during the 2022 to 2023 season.

A housing order was introduced in mid-November and since then detections in farmed flocks have decreased substantially. Wild bird detections are frequent across the country although with some reduction compared to earlier in the season.

As reported in the World Organisation for Animal Health situation reports, detections of A(H5N1) clade 2.3.4.4b in poultry and wild birds have decreased globally since December 2022. However, a significant number are still being reported; and, for the first time, such detections have been made in South America.

Epidemiology in mammals

A programme of mammalian surveillance (APHA) detected influenza A(H5N1) in 14 out of 134 mammals collected since October 2021. This includes one detection in Scotland and one detection in Wales since commencement of enhanced mammalian surveillance in January 2023.

International surveillance data of non-avian A(H5N1) detection shows repeated findings of spillover into mammalian species, though mammalian surveillance varies internationally. There are reports of potential transmission in mink and investigation into possible transmission in sea lions continues.

Knowledge gaps assessment

An assessment of the current knowledge gaps was produced through a UKHSA convened meeting of expert stakeholders (part 1). The assessment includes surveillance, research and evaluation studies relating to levels 1 to 3 of an avian influenza outbreak. UKHSA and APHA have both initiated enhancements to surveillance.

Reports from Technical Group members

The University of Edinburgh reported on preliminary analysis of the phylogenetics of the avian outbreak. The Pirbright Institute (FluMap Consortium) reported on the progress of phenotypic studies on thermostability and other in vitro characteristics of current UK viruses. These data will be shared following review in full at the next Technical Group meeting.

Risk

The risk assessment of 30 January 2023 remains appropriate. The risk to human health relates to both the continued high levels of transmission in birds, increasing the opportunity for mammalian and human exposures, and the apparent ability of the successful clade (2.3.4.4b) to cause direct spillover infection with opportunities therefore for adaptation and reassortment. There is very limited evidence of mammalian transmission to date, but this is a critical gap to address with enhanced surveillance.

This is an elevation of risk compared to the risk before the emergence of this clade, but there is no evidence of currently increasing human health risk through genomic or epidemiological surveillance. The risk to the UK is likely to be greater from imported than domestic cases; however, UK-based surveillance can be used to refine understanding of the human health threat as well as to detect events within the UK should they occur. The outbreak continues to be assessed as at level 3.

Preparedness

To facilitate preparedness, planning and improvements to surveillance, scenarios of early human transmission are being developed. Parameters for early human outbreak scenarios were agreed by the Technical Group.

Part 1. Knowledge gaps assessment and prioritisation (outbreak levels 1 to 3)

This assessment includes needs for research, evaluation and surveillance or public health studies focusing on those which should be initiated at levels 1 to 3 of an avian influenza outbreak. From level 4 onwards, pandemic research portfolio considerations would apply.

Surveillance and testing

What is the performance of lateral flow devices for detecting influenza A (H5N1)?

Initiate at risk level: 3

Status: priority gap; planned (UKHSA)

What is the optimal H5N1 specific serological assay?

Initiate at risk level: 3

Status: commenced (UKHSA)

Is asymptomatic or mild infection occurring in those who are directly exposed and what is the immune response in such individuals?

Initiate at risk level: 3

Status: commencing February 2023 (UKHSA surveillance asymptomatic exposed individuals)

Can we provide assurance that severe infection is not occurring within the UK?

Initiate at risk level: 3

Status: commenced (UKHSA updated guidance to the NHS on testing and subtyping influenza in intensive care units)

Is there transmission occurring between mammals (requiring expanded mammalian sampling to a designed framework)?

Initiate at risk level: 3

Status: priority for action

Virological characterisation

What underlies the host range expansion in birds and what implications does it have for human health?

Initiate at risk level: 2

Status: priority for action

What are the mutations and genomic profiles that we should consider as increasing risk to human health?

Initiate at risk level: 1

Status: Commenced (APHA, UKHSA, FluMap until 1 April 2023); priority for further action

Do any circulating viruses show evidence of increased risk to human health?

Initiate at risk level: 1

Status: commenced – genomic horizon scanning (UKHSA and APHA), in vitro (FluMap until 1 April 2023; priority for action); in preparation – in vivo (UKHSA)

Transmission

How stable is the virus in the environment and what are the environmental factors which increase the risk to human health (for example, seasonal variation, exposure to ultraviolet radiation, ventilation, migratory patterns)?

Initiate at risk level: 2

Status: FluMap until 1 April 2023

What is the risk of bird to human transmission in different environments and at different levels of exposure?

Initiate at risk level: 1

Status: in process (APHA)

In the event of any human case, can we detect any transmission to contacts?

Initiate at risk level: 3

Status: available if required (UKHSA)

Modelling

What are our estimates for key parameters for modelling of the early outbreak?

Initiate at risk level: 3, with ability to collect data and refine rapidly at higher levels

Status: in process (UKHSA)

What is our estimate of prevalence conditional on detecting a case through different surveillance approaches?

Initiate at risk level: 3

Status: in process (UKHSA)

What are the reasonable worst-case scenarios for transmission and time to detection?

Initiate at risk level: 3

Status: in process (UKHSA)

What would be the impact of public health measures, including border measures, on an outbreak?

Initiate at risk level: 3

Status: in process (UKHSA)

Behavioural and social sciences

How can uptake of personal protective equipment (PPE) and testing be improved in those at risk?

Initiate at risk level: 2

Status: under discussion

What are the barriers and facilitators for antiviral use in those who are occupationally exposed?

Initiate at risk level: 2

Status: in process (UKHSA)

Vaccines and therapeutics

Further detailed scoping of countermeasures research needs is being undertaken.

Initiate at risk level: 2

Status: preparatory work on antiviral testing has commenced (UKHSA); scoping and planning of vaccine related studies is a priority for action

Part 2. Epidemiology update

2.1 Current epidemiological situation

There have been unprecedented levels of avian influenza circulating in England since 2021. The dominant subtype currently circulating in avian species across England is highly pathogenic avian influenza (HPAI) A(H5N1).

Avian epidemiology

Since the start of the 2022 to 2023 season, APHA has confirmed HPAI A(H5N1) in avian species at 145 premises in England and in 656 wild birds from 413 locations in England. As of 14 February 2023, this represents 15 new infected premises and 209 further detections in wild birds since the last update (15 December 2022). One detection of A(H6N2) avian influenza was confirmed at an infected premises in the North-West of England. More information on the current situation and testing policies is published on GOV.UK.

A national housing order for poultry was introduced on 7 November 2022, a relatively low number of infected premises have since been reported in England with a sharp decline observed from mid-January 2023 (Figure 1).

Detections of avian influenza in wild birds continue and have been more geographically widespread (Figure 1). Whilst the number of wild bird detections has decreased compared to earlier in the reporting season, positivity remains high and the joint Defra and APHA assessment is that there are continued high levels of influenza transmission in UK wild birds.

Figure 1. Confirmed detections of avian influenza in poultry and wild birds by setting type in England from 1 October 2022 to 14 February 2023. Data provided by APHA

The data used in this graph can be found in the accompanying spreadsheet.

Mammalian detections

APHA surveillance has detected influenza A(H5N1) in 14 of 134 wild mammals collected since October 2021 (Figure 2). The majority of these are retrospective detections (12 out of 14) from samples collected before January 2023. Prospective APHA surveillance since in January 2023 has detected influenza A(H5N1) in 2 mammals.

Of these 14 detections, 4 were in foxes in England, one was a fox in Wales, and from the 9 detections in Scotland, 4 were in otters, 4 were in seals and one in a fox.

Figure 2. Detections of A(H5N1) in wild mammals collected between 1 October 2021 and 14 February 2023 through APHA surveillance programme

The data used in this graph can be found in the accompanying spreadsheet.

There have also been continued reports of detections in mammals internationally (Figure 3). These do not appear to be increasing in frequency though there is no standardised approach to surveillance or reporting. Die-off of sea lions with H5N1 detections in Peru was noted (Gamarra-Toledo and colleagues, 2023. No sequence data are yet available, transmission between sea lions is possible but not confirmed.

Figure 3. International reports of mammalian A(H5N1) detections collated through epidemic intelligence surveillance from 1 January 2020 to 14 February 2023

The data used in this graph can be found in the accompanying spreadsheet. Data is sourced from the Emerging Infections and Zoonoses epidemic intelligence scanning database from official and unofficial reports (including media reports) which may include a small number of duplicate entries due to incomplete information.

Human potential exposures

Human exposures to avian influenza are managed by UKHSA Health Protection Teams (HPTs) and recorded in HPZone, as detailed in technical briefing 1. Individual exposures to avian influenza are risk assessed in accordance with UKHSA guidelines to determine the level of management required.

Between 1 October 2022 and 14 February 2023, 2,310 exposure episodes were entered. Prior to the housing order being implemented, the distribution of probable exposures was concentrated in the East of England and the East Midlands (Figure 4), since this intervention, the number of incidents and probable exposures in these regions has significantly reduced. It should be noted that HPT workload and data entry prioritisation took place in some regions at the same time which may affect data reporting via HPZone.

Figure 4. Exposures reported on HPZone from 1 October 2022 to 14 February 2023

The data used in this graph can be found in the accompanying spreadsheet.

Information is also collected by HPTs using surveillance forms, as described in technical briefing 1, with caveats on completeness and lag. Between 1 October 2022 and 14 February 2023, information was returned for 249 (44.5%) out of 559 incidents this season and documented 3,120 exposure events (individuals may be recorded in more than one event if they are exposed multiple times).

Over half of the surveillance forms received from HPTs relate to wild bird incidents (142 out of 249 forms returned). Wild bird incidents often involve fewer exposed individuals.

Personal protective equipment (PPE) use was reported in 639 (20.5%) exposures. Antiviral prophylaxis was reported for 296 (9.5%) exposures. Symptoms were reported following 68 (2.2%) exposures, with 50 symptomatic swabs being carried out (73.5% of those eligible); all tests were reported H5N1 negative. Forty asymptomatic swabs were performed and reported as part of an enhanced surveillance pilot from consenting individuals with no H5N1 detected.

There remain no human detections of influenza H5 in England over the 2022 to 2023 season.

2.2 Human cases

In addition to the human case reported last season from England (Oliver and colleagues, 2022), 5 human cases of A(H5N1) 2.3.4.4.b have been reported by WHO since December 2021. This includes one case from the United States of America (USA), 2 cases from Spain, one case from Vietnam and one case from China.

All 4 cases from Europe and the USA reported mild symptoms or were asymptomatic when tested. The cases from the USA and Spain were involved with poultry work including culling of poultry and disinfection of infected premises.

The cases from China and Vietnam were severe with a fatality reported in the case from China. Both cases had exposure to poultry.

No human-to-human transmission has been reported between any human A(H5N1) cases.

One additional case of A(H5Nx) was reported from Ecuador in January 2023, however subtype and clade information is still unknown for this case.

UKHSA continues to carry out horizon scanning for epidemiological reports relevant to emerging influenza in humans and animals.

2.3 Capability to detect human cases of H5N1

UKHSA receives influenza positive clinical samples referred from NHS and regional public health laboratories (PHLs) for whole genome sequencing, virus isolation and antigenic characterisation, year-round. This is described in further detail in technical briefing 1. The sensitivity of this system for detecting emerging viruses is currently under assessment.

Between 3 October 2022 and 14 February 2023, 120 samples which were unsubtypable locally or at regional labs were referred to the UKHSA Respiratory Virus Unit. Of these, 73% (n=88) were characterised as seasonal H1 or H3 viruses, with 16% (n=19) having no virus detected and 8% (n=10) as having detectable but insufficient viral load to achieve a subtyping result. Characterisation is ongoing for 3 samples.

Part 3. Genomic surveillance

3.1 UK avian and mammalian data

Complementary genomic analysis is currently being performed by both APHA and UKHSA using genomic sequencing data shared by APHA. The following analysis is reported by APHA and refers to UK genomes only.

Across the whole period of genomic surveillance of the current influenza A (H5N1) outbreak to date, as of 17 February 2023 APHA report that they have assessed 535 influenza genomes from poultry and wild bird detections.

Over the same period, 7 influenza genomes from mammalian detections have also been analysed, and a similar profile of genetic alterations have been observed, as with the avian sequences, with the exception of the polymerase basic protein (PB2) E627K mutation which was identified in 6 out of the 7 mammalian sequences, and has only been detected once in UK avian sequences.

From the 2022 to 2023 season, 222 genomes are available from poultry and wild bird detections in the UK. Whilst these sequences do possess a number of genetic changes associated with mammalian adaptation, the nature and prevalence of such mutations have not increased since the beginning of the current epizootic in October 2021.

For the 2022 to 2023 season, one mammalian genome is available which does not demonstrate the presence of any adaptive mutations that are not already present in the sequences obtained from avian detections (including in the PB2 and haemagglutinin (HA) proteins).

Note is made of the I390M HA mutation described in a recent Eurosurveillance letter to the editor. This mutation has not been detected in UK mammalian genomes.

Part 4. Preparedness

4.1 Human infection scenario parameters

To facilitate preparedness, planning and improvements to surveillance, scenarios of early human transmission are being developed. The Technical Group reviewed and agreed the following parameters to be used in preliminary scenarios:

To date, there has been no or little evidence of sustained human-to-human transmission of avian influenza viruses because tissue tropism limits virus transmission from birds to humans and similarly, from human to human. There has been some evidence of small family clusters and potential for limited nosocomial transmission (Yang and colleagues, 2015; Aditama and colleagues, 2012). By definition, sustained human-to-human transmission of the virus would yield an R number above one, but past outbreaks are not a good guide to refining this further. We judge that looking at scenarios where the R number is between 1.2 and 2 (or where doubling times are roughly between 5 days and 20 days) is a useful start.

Two scenarios with different severity will be developed. We define a mild scenario as one where the infection-fatality rate (IFR) is similar to that of COVID-19 in mid-2021, around 0.25%. This is roughly equivalent to the severity of the 2009 H1N1 outbreak, though case fatality rate (CFR) estimates for that range from 0.03% in England (Donaldson and colleagues, 2009) to 5% in Argentina (Vaillant and colleagues, 2009). There are very few studies with estimates of an infection-hospitalisation rate (IHR), so for simplicity we judge that 1% is a useful benchmark.

For a more severe scenario, we base our parameters on the 1918 pandemic, which had an IFR of around 2.5% (Murray and colleagues, 2006). We also assume in this scenario an IHR of 5%. Although various H5N1 outbreaks have much higher fatality estimates, these are not examples of sustained human-to-human transmission and are therefore not directly comparable (for example see Li and colleagues, 2008; Poovorawan and colleagues, 2013). A severe scenario might also be associated with an age profile that skews harm less towards older people. For example, the 1918 outbreak led to an excess of deaths in younger adults. Such an occurrence today, even with a fairly low IFR could lead to significant behavioural differences relative to the recent pandemic experience.

Taking these parameters, UKHSA will continue to build our understanding about how different surveillance systems might detect cases if there is sustained human-to-human transmission of the virus.

Sources and acknowledgments

Data sources

Data relating to animal health surveillance and investigations taking place across England obtained from the APHA. This includes data from wild bird surveillance, notifiable disease reports at infected premises and detections in mammals.

Surveillance forms are completed by UKHSA HPTs for each confirmed setting (includes both poultry and wild bird settings); this includes the follow-up of exposed persons and details of exposure. Data is enhanced with laboratory records for respiratory testing held by UKHSA.

Details of exposed individuals are also collected from HPZone, the UKHSA case management system​.

International surveillance data of human cases of avian influenza is reported by the WHO under the International Health Regulations and routinely collated by UKHSA.

Authors of this report

Rachel Abbey, Carolina Arevalo, Ian Brown, Alexander Byrne, Fernando Capelastegui, Lorenzo Cattarino, Meera Chand, Fergus Cumming, Neil Cunningham, Eileen Gallagher, Susan Hopkins, Munir Iqbal, Joe James, Angie Lackenby, Anissa Lakhani, Thomas Peacock, Andrew Rambaut, Jess Tarrant

Contributors

• UKHSA Behavioural Science and Insights team
• UKHSA Data Science and Geospatial team
• UKHSA Genomics Public Health Analysis
• UKHSA Respiratory Virus Unit
• UKHSA Research and Evaluation
• UKHSA Research Support and Governance Office
• UKHSA Rapid Investigation Team
• Animal and Plant Health Agency
• Imperial College London
• Francis Crick Institute
• The Pirbright Institute

Avian Influenza Technical Group

The Avian Influenza Technical Group includes members with expertise in clinical infectious diseases, clinical research, epidemiology, genomics and virology:

• Meera Chand (Chair), UKHSA
• Wendy Barclay, Imperial College London
• Alexander Byrne, APHA
• Ashley Banyard, APHA
• Eileen Gallagher, UKHSA
• Ian Brown, APHA
• Neil Ferguson, Imperial College London
• Yper Hall, UKHSA
• Bassam Hallis, UKHSA
• Susan Hopkins, UKHSA
• Katja Hoschler, UKHSA
• Munir Iqbal, The Pirbright Institute
• Joe James, APHA
• Angie Lackenby, UKHSA
• Nicola Lewis, Francis Crick Institute
• Nicholas Loman, UKHSA and University of Birmingham
• Thomas Peacock, Imperial College London
• Richard Puleston, UKHSA
• Andrew Rambaut, University of Edinburgh
• Nick Watkins, UKHSA
• Maria Zambon, UKHSA
• Esther Robinson, UKHSA
• Alastair McGregor, UKHSA
• Andre Charlett, UKHSA
• Fergus Cumming, UKHSA
• Helen Roberts, Defra

Acknowledgements

The authors are grateful to those teams and groups providing data for these analyses including:

• Animal and Plant Health Agency
• Pirbright Institute
• Imperial College London
• University of Edinburgh