Research and analysis

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

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

Summary

1. Through enhanced surveillance of poultry workers, there have been asymptomatic detections of influenza A(H5N1) in 2 individuals with exposure to infected farmed birds at a single site. As of 23 May 2023, 85 individuals from 5 infected farming premises have been tested through this surveillance programme.
2. Based on timing, one human detection may represent contamination of the respiratory tract, while the second is more uncertain and could be consistent with infection. Precautionary clinical and public health measures (isolation, antivirals and contact tracing) were applied in the second detection.
3. Viral genome sequence is available from birds on the premises linked to the human detections, and from the second detection. A partial genome is available from the first detection. All 3 genomes are influenza A(H5N1) clade 2.3.4.4b, with the complete genomes being classified as UK genotype AIV48, also known as the A/gull/France/22P015977/2022-like genotype. Details and accession numbers for the genomes are provided in this briefing. Data has also been shared with the FLUMAP consortium for consideration of phenotypic assessment.
4. There is no evidence of human-to-human transmission and these findings do not change the assessment of human health risk, which remains at level 3 (see also the qualitative assessment on influenza A(H5N1) infections in non-avian UK wildlife from the multi-agency Human Animal Infections and Risk Surveillance (HAIRS) group).
5. Twelve human cases of A(H5N1) have been reported by the World Health Organization (WHO) since December 2021. Ten of these cases are from clade 2.3.4.4.b, 2 from clade 2.3.2.1.c, and in one case, the subtype is to be determined. This includes 3 new cases (the 2 detections in England and one case in Chile) since the last technical briefing. There is no evidence of human-to-human transmission from these cases.
6. Since the last technical briefing there have been detections of influenza A(H5N1) in a further 6 premises and 68 further wild bird locations. The poultry housing order was lifted on 18 April 2023. Detections in infected premises remain at low levels compared to earlier in the season. Wild bird detections continue to be geographically widespread across England but with strong association with gull and tern species.
7. An APHA-led programme of mammalian surveillance detected influenza A(H5) in 23 out of 247 wild mammals collected since October 2021 in the UK. This includes 6 detections since commencement of enhanced mammalian surveillance in January 2023. Since the last technical briefing (data as of 15 March 2023), 18 wild mammals have been tested with no new detections of influenza A(H5N1).
8. International surveillance data continues to show spillover into mammalian species, though mammalian surveillance varies internationally. There are no new outbreaks with confirmed mammalian transmission since those reported in the last technical briefing, although some investigations continue. Note is made of a report from the Netherlands in which there was virological and serological evidence of influenza A(H5N1) infection in a variety of wild carnivore species (Chestakova and colleagues, 2023).

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

Part 1. Asymptomatic avian influenza surveillance of poultry workers

1.1 Surveillance update

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.

1.2 Surveillance results

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.

Detection 1

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.

Detection 2

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.

1.3 Contact tracing

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.

1.4 Genomics surveillance

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.

Table 1. Mutational profile of recent detections relative to AIV48 reference (EPI_ISL_13782459: A/chicken/England/085598/2022)

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.

Protein or segment	Amino acid Position	AIV48 reference	Chicken from farm	Detection 1	Detection 2	Percentage (%) of UK AIV48 sequences with mutation
PB2	74	G	S	-	S	6.9
PB2	699	K	R	-	R	13.8
PB1	181	I	M	-	M	75
PB1	362	M	L	-	L	6.3
PB1	331	E	V	-	V	0
PB1	618	E	K	-	K	0
PB1	648	A	S	-	S	15.6
PB1	175	N	D	-	D	78.1
PA	547	D	N	-	N	0
HA	87*	T	I	I	I	97.5
HA	88	R	G	G	G	5.1
HA	104	D	G	G	G	15.4
HA	526	I	V	V	V	0
NP	310	S	S	-	N	0
NA	2	N	S	-	-	6.67
NA	304	V	I	I	I	6.67
M1 (MP)	224	S	N	-	N	0
NS1 (NS)	180*	I	V	-	V	97.5

Part 2. Avian infections

2.1 Current epidemiological situation

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

Avian epidemiology

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.

Figure 1a. Confirmed detections of avian influenza at infected premises by quarter in England from 1 October 2022 to 23 May 2023. Data provided by APHA

Figure 1b. Confirmed detections of avian influenza in wild birds by quarter in England from 1 October 2022 to 23 May 2023. Data provided by APHA

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.

Part 3. Mammalian infections

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).

Figure 2. Detections of A(H5N1) in wild mammals collected between 1 October 2021 and 23 May 2023 through APHA surveillance programme

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.

Figure 3. International reports of mammalian A(H5N1) detections collated through epidemic intelligence surveillance from 1 January 2021 to 23 May 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. Event date indicates collection date where known, or notification date when collection date unknown.

Potential human exposures

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).

3.2 Human cases

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.

Table 2. Number of influenza A(H5N1) and A(H5) human cases by country and clade since December 2021, as of 23 May 2023

Country	A(H5N1) clade 2.3.4.4.b	A(H5N1) clade 2.3.2.1.c	A(H5) confirmed
England	3	0	0
Spain	2	0	0
US	1	0	0
China	2	0	0
Ecuador	1	0	0
Vietnam	0	0	1
Cambodia	0	2	0
Chile	1	0	0
Total	10	2	1

Cases from influenza A(H5N1) clade 2.3.4.4.b

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.

3.3 Influenza samples referred to UKHSA for characterisation

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.

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.

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.

Authors of this report

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.

Contributors

• UKHSA Data, Analytics and Surveillance Team
• UKHSA Data Science and Geospatial team
• UKHSA Genomics Public Health Analysis
• UKHSA Rapid Investigation Team
• UKHSA Respiratory Virus Unit
• UKHSA Research and Evaluation
• UKHSA Research Support and Governance Office
• UKHSA Emerging Infections and Zoonoses 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
• Ashley Banyard, APHA
• Wendy Barclay, Imperial College London
• Ian Brown, APHA
• Alexander Byrne, APHA
• Andre Charlett, UKHSA
• Fergus Cumming, UKHSA
• Neil Ferguson, Imperial College London
• Eileen Gallagher, UKHSA
• Natalie Groves, UKHSA
• Yper Hall, UKHSA
• Bassam Hallis, UKHSA
• Susan Hopkins, UKHSA
• Katja Hoschler, UKHSA
• Munir Iqbal, The Pirbright Institute
• Joe James, APHA
• Rowland Kao, University of Edinburgh
• Angie Lackenby, UKHSA
• Nicola Lewis, Francis Crick Institute
• Nicholas Loman, UKHSA / University of Birmingham
• Paul Millar, Health and Social Care Northern Ireland
• Thomas Peacock, Imperial College London
• Richard Puleston, UKHSA
• Oliver Pybus, Royal Veterinary College / University of Oxford
• Andrew Rambaut, University of Edinburgh
• Helen Roberts, DEFRA
• Anika Singanayagam, UKHSA
• Nick Watkins, UKHSA
• Christopher Williams, Public Health Wales
• Anthony Wilson, Food Standards Agency
• Maria Zambon, UKHSA

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