Pilot of asymptomatic swabbing of humans following exposures to confirmed avian influenza A(H5) in avian species in England, 2021/2022

Abstract A programme of asymptomatic swabbing was piloted in 2021/2022 in England to further understand the risk of human infection with avian influenza in exposed individuals and to evaluate this surveillance approach as a public health measure. There were challenges in deploying this pilot that will need to be addressed for future seasons. However, there was one detection of avian influenza A(H5N1) in a human despite low uptake in eligible exposed persons. Future use of asymptomatic swabbing could help provide an evidence base to quantify asymptomatic infection, quickly identify signals of increased animal to human transmission and improve public health preparedness.


| INTRODUCTION
There have been unprecedented and increasing levels of avian influenza (AI) detected in bird species across England and globally since 2020, 1 particularly A(H5N1) of clade 2.3.4.4b. 2,3 AI viruses such as A(H5N1) have been previously associated with severe human disease in infected persons, 4 though generally, infections have been sporadic and principally focussed among those who are directly exposed to infected birds. 5 In England, AI detections in birds confirmed by APHA (Animal and Plant Health Agency) are notified to UKHSA (UK Health Security Agency) Health Protection Teams (HPTs) who undertake public health actions 6,7 including identification of exposed persons (EPs), provision of advice on PPE (personal protective equipment), and for specific haemagglutinin subtypes including H5, H7 or H9, antiviral prophylaxis and health monitoring. 7 PCR testing is recommended in EPs who develop symptoms. However, the detection of A(H5N8) clade 2.3.4.4b in exposed poultry workers in Russia demonstrated the potential for asymptomatic infection. 8,9 In the context of an increasing number of bird detections 1  Once HPTs had agreement and consent from the EP, swab kit delivery and collection was organised. Samples were collected in viral transport media and returned in secure postal packaging for testing at UKHSA laboratories using real-time PCR assays to detect influenza A and H5.
Nasal-pharyngeal swabs were collected through self-swabbing or rarely by a health professional at home or away from the infected site, to avoid the risk of environmental contamination. This offer did not replace testing following the development of influenza compatible symptoms during the follow-up period.
Surveillance forms were completed for each incident, routinely collated within UKHSA and processed into a secure dataset. Individual person exposure records were linked to UKHSA laboratory respiratory testing information. Person exposures included in this analysis were those who met the eligibility criteria above between 01 December 2021 and 31 March 2022 and had recorded data including incident type, EP role, region, symptom status, use of PPE and antivirals, swabbing status and result for each person exposure (some EPs had multiple separate exposures).

| Data analysis
Due to small numbers in the EP occupational category data, roles were aggregated to disease control and roles not in disease control.   South East were combined due to small numbers. Age and sex are not routinely collected so could not be included.
Descriptive analysis of eligible person exposures (due to the possibility of individuals having multiple exposures) was carried out to summarise exposure characteristics (Table 1).
Univariate logistic regression was used to assess associations between asymptomatic swabbing and the following: region, incident type, EP role and receipt of antiviral prophylaxis (Table 2). other individuals associated with the same incident or with direct exposure to the case. This was the first human detection of A(H5) in

| RESULTS
England and would not have been detected in the absence of this pilot study.
Regional association with likelihood of asymptomatic swabbing may be explained by specific local factors and barriers. Increased uptake in the South West may be due to local awareness following the reported human case in the region. Additionally, the South West were proactive adopters of the pilot and used a postal system early on which was found to be successful. The higher uptake in the South West demonstrates that, if adopted as a surveillance strategy, there are opportunities to increase overall uptake of asymptomatic testing.
A reduced likelihood in uptake in those exposed to WB detections was expected. The extent of these exposures often varies, and individuals involved are from a wider range of backgrounds (including non-occupational exposures) who are likely to have perceived the risk of exposure differently. Notification of EPs exposed at WB incidents was often delayed beyond the 10-day follow-up period as WB testing is carried out for surveillance purposes, unlike the rapid testing of IPs, reducing the eligible cohort in this group. Qualitative research is being undertaken to assess the underlying factors such as knowledge and attitudes as well as logistical and workload challenges associated with the low uptake in different regions and incidents in order to improve future uptake of asymptomatic selfswabbing.

| CONCLUSION
Following a human detection of A(H5N1) through this pilot, surveillance has detected other infections among EPs in the United States and Spain. In the context of high burden of disease in birds and the need to better understand risk to humans, we recommend the introduction of an asymptomatic testing programme, which has also since been included in updated recommendations from WHO. 1 Further work is needed to develop the system including incorporating behavioural evidence to increase uptake. This will help identify early emergence of AI viruses from birds to humans and inform public health responses at an earlier stage.