Monitoring project on human avian influenza (AI) infections in contact with AI-infected animals

Since autumn 2021, there have been ongoing outbreaks of highly pathogenic avian
influenza virus (HPAI) A(H5N1) clade 2.3.4.4b among poultry and wild birds
worldwide and also in the Netherlands. This is a different variant of the
A(H5N1) virus than the variant that has been circulating in China and Southeast
Asia for several years and has led to infection in several hundred people
there, often with serious illness and regularly leading to death. The current
A(H5N1) clade 2.3.4.4b is now circulating worldwide and also in China.
To prevent transmission to other poultry farms, infected poultry are culled by
the NVWA. To date, these mainly concern separate introductions and transmission
between farms appears to be very limited. While contamination of poultry farms
during previous seasons was geographically strongly correlated with
waterfowl-dense areas and was limited to certain types of poultry farms, both
the geographical distribution and the diversity of infected poultry farm types
are currently increasing. Outbreaks also occur all year round and are no longer
seasonal. This ongoing transmission is likely due to contamination via infected
wild birds. Wild birds with HPAI are reported very frequently, often resulting
in significant mortality. In Spain, a mink farm was recently infected with the
virus, whereby mink-to-mink transmission cannot be ruled out (Agüero et al.,
2023).
Seven human cases of HPAI A(H5N1) 2.3.4.4b viruses have been reported
worldwide. (WHO data as of December 21, 2022). These viruses belong to the same
clade A(H5N1) viruses that have recently been detected in poultry and wild
birds in the Netherlands. It is a worrying fact that in several countries,
including the Netherlands, wild mammals are regularly infected with these clade
A(H5N1) viruses and adaptation mutations in the virus for replication in
mammalian cells are found, as is also the case with the previously mentioned
kept minks. This means that the risk of transmission from bird to human and the
development of the human-adapted A(H5N1) virus is estimated more realistically.
In the Netherlands, 27 infected wild mammals, including many foxes, were found
in 2021 and 2022. An estimated 600 infected and mostly dead sea lions have
recently been found in Peru. More than 100 infected mammals from more than 10
species have been found in the US.

Problem/challenge
Adaptation of the HPAI A(H5N1) virus to infection and multiplication in
mammalian cells allows effective transmission to humans. The risk of infection
with HPAI A(H5N1) is greatest for people with a high degree of (unprotected)
exposure to infected animals. When the virus mutates to efficient human-adapted
infection and virus replication or reassortment of an HPAI A(H5N1) with a human
seasonal influenza virus occurs, effective human-to-human transmission may
become possible, posing a risk to public health. It is therefore important to
detect possible infections with HPAI A(H5N1) in humans in good time.
Currently, passive monitoring only takes place of exposed persons who develop
respiratory complaints, but not of exposed persons without complaints. It is
not known how many people develop respiratory complaints after exposure to HPAI
virus (including A(H5Nx) and (A(H7Nx)). In the context of passive monitoring,
there is urgent advice to persons who develop respiratory complaints after
exposure to infected poultry to have themselves tested for HPAI virus infection
(LCI Avian Influenza scenario, Appendix 4, 2022). Among those who have had
themselves tested (until 2021 a few people annually, in 2022 41 people, in 2023
(t /m April 15) one person) no HPAI virus has been detected so far. As
mentioned, it is not known which part of the total number of exposed persons
develops respiratory complaints and subsequently undergoes testing.

In addition to the aforementioned passive monitoring of high-risk persons with
respiratory complaints after exposure to HPAI, this project aims to set up
active monitoring (exclusion diagnosis) in high-risk persons without
respiratory complaints in order to gain a better insight into possible
transmission of the HPAI virus ( including A(H5Nx), (A(H7Nx)) to humans,
following the advice of the Expert Council-Zoonoses of 9th of May 2022.

Persons from the target group are advised to collect a throat and nose swab and
a finger prick blood as soon as possible after exposure to proven infected
animals and to send these to RIVM together with a self-completed collection
form. It is important that the throat and nasal swab are taken under hygienic
conditions, i.e. not immediately after work at the infected company, but only
after showering and putting on clean clothes and in the home. The collection
form will include questions about demographic data, possible complaints and
symptoms and the degree and type of exposure to infected poultry. RIVM/IDS will
perform influenza virus diagnostics with PCR on the submitted swabs: generic
influenza virus type A and B detection and subtyping H1pdm09, H3 and H5. Based
on the results, it is determined whether there is a probable infection with
HPAI H5 virus. This is the case with a positive influenza A and H5 PCR. In the
event of a positive influenza A PCR and subtype negative for H1pdm09, H3 and
H5, depending on the viral load, additional testing is first done and a repeat
sample may be requested (via the GGD) to determine which subtype of virus is
involved. In both cases, the virus is sequenced and the sample is cultured for
definitive laboratory diagnosis. The diagnostics will be performed twice a week
and will be included in the routine of regular influenza surveillance.
The finger blood is only used as a reference serum in case of a positive
laboratory diagnosis for H5 (or other HPAI virus).

This research is of primary public health importance and has no direct benefit
to the individual participant. Participants are asked to complete one short
questionnaire. In addition, the participants are asked to take a throat and
nasal swab and to take some blood by means of a finger prick.