Investigation into the risk to human health of avian influenza (influenza A H5N1) in England: technical briefing 4

Updated 2 June 2023

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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 23 May 2023 (or as specified in the text) to allow time for analysis.

The UK risk assessment remains at level 3 (limited mammalian transmission, low confidence) as described in the previous technical briefing.

On notification of infected poultry premises with highly pathogenic influenza A virus (HPAIV) infection, UKHSA deploys the Rapid Investigation Team. The team obtains consent from those who are working or otherwise present inside the biosecurity perimeter line, observes a baseline self-swab (day 0), and provides self-swabs for postal return on day 2, 5 and 8. The protocol will be published on GOV.UK in due course.

The programme launched in March 2023. As of 23 May 2023, 85 individuals have participated from 5 sites with ongoing influenza A (H5N1) outbreaks and culling activities. This equates to 70% of persons known to have been in the biosecurity area at those sites, including farm workers and additional workers undertaking culling.

One hundred and twenty-two individuals were identified as having been within the biosecurity area on the 5 included sites to date. Of these, 85 participated in the surveillance programme. Two human detections of influenza A (H5N1) 2.3.4.4b have been confirmed from one site.

Day 0 is the day of recruitment to the study and usually occurs on a day that the individual is working at the infected premises. Influenza A was detected on a single day 0 sample taken under supervision outside the biosecurity perimeter (H1 and H3 subtypes not detected, H5 detected by polymerase chain reaction (PCR) testing). Virus culture was unsuccessful. Genomic analysis confirmed Influenza A (H5N1) 2.3.4.4b with the partial genome available consistent with AIV48.

Two subsequent nose and throat samples on day 2 (self-taken) and day 3 (taken by a healthcare professional) were negative for influenza A. The individual remained asymptomatic throughout.

The results to date, in the context of exposure of the individual on the farm on the same day as swab collection, suggest this detection could be due to temporary contamination of the upper respiratory tract acquired through exposure to infected birds or the surrounding environment, rather than a sustained infection.

The second individual was also recruited during a day working on the infected premises, day 0. Following negative tests on day 0 and day 2, the individual collected 2 further self-taken swabs on day 4 and day 5 (not fully consistent with the protocol).

Influenza A was detected by real time (RT)-PCR in both day 4 and day 5 samples in 2 UKHSA laboratories; subtyping was negative for H1 and H3, and positive for H5, on 2 independent H5-specific assays (Spackman and colleagues, 2002; Slomka and colleagues, 2007). These detections were toward the limit of detection (cycle threshold (Ct) value greater than 30). Virus culture was unsuccessful. A full genome was sequenced and confirmed influenza A (H5N1) 2.3.4.4b genotype AIV48. A further swab was collected from the individual which tested Influenza A and H5 negative.

The individual remained asymptomatic throughout. These results are considered of uncertain significance, but could be compatible with infection, on which basis precautionary public health measures were taken.

For detection 1, passive surveillance of close contacts was undertaken. All close contacts remained clinically asymptomatic. Other contacts were followed up as part of the study.

For detection 2, contact tracing was commenced on a precautionary basis and contacts were managed depending on their risk exposure level, including active or passive surveillance, isolation, antivirals and testing. Twenty contacts were identified. All remained asymptomatic. Fifteen of 20 contacts were accessible for testing and all tested negative.

Viral genome sequencing was performed on one poultry sample from the farm and the 2 human detections. Sequence data for all 8 segments was produced for the poultry sample (Global Initiative on Sharing All Influenza Data (GISAID) accession number EPI_ISL_17657734) and the second human detection, referred to as detection 2 (GISAID EPI_ISL_17736649). Partial sequence data (haemagglutinin (HA), neuraminidase (NA) segments only) was produced for the first human detection, referred to as detection 1 (GISAID EPI_ISL_17736680).

The HA segment was available for the avian case and both human detections. All 3 were identified as clade 2.3.4.4b, which is the current predominant H5 HPAIV clade circulating in the UK and globally. Genotype could be established for the avian sample and detection 2 as all 8 segments were sequenced successfully. These were identified as genotype AIV48, also known as the A/gull/France/22P015977/2022-like genotype. Genotype AIV48 was first detected in the UK in June 2022, with low-level detection across Great Britain (England, Scotland and Wales) and Crown Dependencies (Isle of Man and Jersey) since then including 25 poultry cases, 3 captive or rehabilitated birds, 11 wild birds and 2 mammals (foxes) for which sequence data is available.

Sequence data available for detection 1 is consistent with genotype AIV48 but cannot be confirmed due to missing gene segments.

Concatenated sequence data for all segments from the 2 complete genomes (avian and detection 2) was placed into a phylogeny with all UK (December 2020 to April 2023) and GISAID H5N1 (November 2016 to April 2023) sequences. The avian and detection 2 sequences from the farm sit within a clade containing other UK AIV48 genomes, along with other European sequences.

The genome sequences were compared to the first AIV48 genome detected in the UK (EPI_ISL_13782459: A/H5N1 A/chicken/England/085598/2022) to identify amino acid substitutions within the sequences. The avian sequence from this poultry farm contains 16 amino acid changes compared to the AIV48 reference sequence, as described in Table 1.

The sequence from detection 2 contains all the non-synonymous changes present in the genome from the avian sample, with one additional mutation (NP: S310N) and at one location, the sequence cannot be called due to insufficient coverage (NA:N2S) (Table 1). The partial sequence data from detection 1 was also reviewed and was consistent with the other 2 genomes where there was sufficient sequence data. No additional mutations were observed in the sequence data available for detection 1.

Variation is expected within each genotype; however, further analyses are ongoing and data has been shared with laboratory partners for the assessment of any phenotypic significance.

A dash (-) indicates insufficient coverage at that position.

An asterisk (*) indicates a mutation that has been identified in the AIV48 reference only and not in other AIV48 genomes.

The dominant subtype circulating in avian species across England continues to be highly pathogenic avian influenza (HPAI) A(H5N1).

From the start of the 2022 to 2023 season, APHA has confirmed HPAI (H5N1) in poultry species at 154 premises in England and in wild birds from 526 locations. Since the last update (data between 15 March 2023 and 23 May 2023) there have been 6 new infected premises and detections at 68 further wild bird locations. Further information on the latest avian influenza situational update in England is published online.

The number of detections at infected premises remains relatively low compared to the period before the housing order was implemented. The frequency of detections of avian influenza in wild birds is relatively low compared to the levels at the start of the reporting period in 2022 but have maintained their geographical spread across England (Figures 1a and 1b). The joint DEFRA and APHA assessment is that there continues to be a high level of influenza transmission in wild birds across the UK.

These maps contain National Statistics data © Crown copyright and database right 2022.

Q4 (2022) = Quarter 4 (1 October 2022 to 31 December 2022)

Q1 (2023) = Quarter 1 (1 January 2023 to 31 March 2023)

Q2 (2023) = Quarter 2 (1 April 2023 to 30 June 2023, data cut-off 23 May 2023)

Supplementary data is not available for these figures to prevent deductive disclosure.

Of 18 wild mammals tested for influenza A(H5N1) since the last update (data as of 15 March 2023) there were no new mammalian detections in the UK. APHA surveillance has detected influenza A(H5) in 23 of 247 wild mammals collected since October 2021 (Figure 2).

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

There are 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.

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. Event date indicates collection date where known, or notification date when collection date unknown.

Human exposures to avian influenza undergo a risk assessment by UKHSA health protection teams (HPTs). These teams manage and record exposures in the outbreak information system HPZone, as detailed in previous technical briefings.

Since the last technical briefing, a further 136 exposure episodes across England were entered into HPZone. Guidance on interpreting HPZone data has been published in previous technical briefings.

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 23 May 2023, information was returned for 283 (41.8%) out of 677 incidents this season (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 (171 out of 283 forms returned). Wild bird incidents often involve fewer exposed individuals.

Personal protective equipment (PPE) use was reported in 730 (22.24%) exposures. Antiviral prophylaxis was reported for 305 (9.29%) exposures. For individuals reporting flu-like symptoms, 51 symptomatic swabs were carried out (73.9% of those eligible in this category); all tests were reported as negative for influenza A(H5).

Twelve human cases of A(H5N1) have been reported by the World Health Organization (WHO) since December 2021. This includes 3 new cases since the last technical briefing (2 detections in England (see section 1), and one case in Chile). No human-to-human transmission has been reported related to these cases. See Table 2 for a summary of cases by country and clade.

Since the last technical briefing, one case has been reported from Chile, and a further 2 cases from England as reported above. The case from Chile was severe and reported to reside in close proximity to a large die-off of marine mammals and birds. Details on other cases can be found in previous technical briefings.

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

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 31 May 2023, 136 samples which were positive for influenza A and not subtypable locally or at regional laboratories were referred to the UKHSA Respiratory Virus Unit. Of these, 80% (n=109) were characterised as seasonal H1 or H3 viruses, with 15% (n=20) having no virus detected and 5% (n=7) as having detectable but insufficient viral load to achieve a subtyping result.

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.

Data on international reports of mammals is sourced from the UKHSA Emerging Infections and Zoonoses epidemic intelligence scanning database from official and unofficial reports (including media reports).

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 World Health Organization under the International Health Regulations and routinely collated by UKHSA.

Rachel Abbey, Wendy Barclay, Paula Blomquist, Ian Brown, Alexander Byrne, Fernando Capelastegui, Lorenzo Cattarino, Meera Chand, Neil Cunningham, Eileen Gallagher, Natalie Groves, Berkin Hack, Katja Hoschler, Susan Hopkins, Kate Howell, Joe James, Angie Lackenby, Anissa Lakhani, Steven Riley, Anika Singanayagam, Nick Watkins.

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

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