First known epidemic of highly pathogenic avian influenza H5N1 in farmed mink

Highly Pathogenic Avian Influenza (HPAI) A(H5N1) is a strain of avian influenza virus that primarily affects birds, particularly poultry. HPAI A (H5N1) is a highly contagious and deadly virus that can cause severe illness and death in birds, including chickens, ducks, geese, and turkeys. It has re-emerged after many months of extremely low prevalence during the coronavirus disease 2019 (COVID-19) pandemic. A recent report in the magazine Eurosurveillance describes an outbreak from a mink farm in Spain caused by clade 2.3.4.4b.

Rapid Communication: Highly Pathogenic Avian Influenza A (H5N1) Virus Infection in Farmed Mink, Spain, October 2022. Image Credit: Cergios/Shutterstock

the bud

The mink farm described here is located in Galicia, northwestern Spain. The initial signs of the outbreak occurred with a sudden increase in the number of deaths in proportion to the total number of mink, with the mortality rate increasing from 0.2 to 0.3% to 0.77%. This occurred in early October 2022 and led to the collection of oropharyngeal swabs from two diseased animals.

These were tested at the Central Veterinary Laboratory (LCV) of Algete (Ministry of Agriculture, Fisheries and Food (MAPA)). While the mink samples did not show traces of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by polymerase chain reaction (PCR) testing, they tested positive for the HPAI virus. This was supported by the identification of pneumonia in the affected animals, which led to bleeding in the lungs.

Sick animals exhibited signs such as anorexia, drooling, salivation, low energy, bleeding from the muzzle, and tremors or loss of balance and coordination, indicating nervous system involvement.

Deaths increased week by week, reaching a peak in the third week of October when more than 4% of animals died. Initially, mortality was observed among animals living near the manure storage barn. These pens showed several mortality hotspots, that is, groups of 2 to 4 pens with 100% mortality in a week or two.

The deaths spread to the adjacent stables until they occurred in all the places where there were mink. As more and more samples were taken from the pens where the most significant number of animals appeared to be dying, high levels of H5N1, as assessed by a low cycle threshold (Ct), were detected in rectal, oropharyngeal or lung samples.

In the second week of October of that year, the Animal Health Services census showed more than 51,000 mink in wire cages inside covered but not fully walled stables. Animals were fed raw fish, poultry by-products, blood meal, and cereals. The poultry waste came from farms and slaughterhouses in Galicia.

How was it detected?

Interestingly, as of January 10, 2023, there were no known outbreaks of avian influenza among farmed birds in this region. However, in the weeks before the mink outbreak, several wild birds were found to be sick or dead from HPAI infection, including some gulls and several gannets. This was a red flag for public health experts to suspect that the mink deaths were related to this virus.

Along with PCR tests to rule out SARS-CoV-2 infection, this led to specific tests for HPAI, which was confirmed to be the culprit.

The virus

Genomic testing at the European Reference Laboratory revealed that the strains belonged to the 2.3.4.4b clade. This has been observed infecting wild birds, especially herring gulls, in Belgium, the Netherlands and France, both in the past and for a few weeks before the Spanish outbreak. However, it has not been reported in Spain prior to this outbreak.

The 2.3.4.4b clade appears to be the result of rearrangement events of several H5N1 genes with the gull-adapted H13 subtype. The mink genotyped strains differed by 8-9 amino acids from the closest genetically related H5N1 variants. Especially noteworthy is the alanine substitution in the PB2 gene that causes an increase in viral polymerase activity after infection of mammalian cells.

So far, this substitution has been observed only once in a European polecat from the Netherlands, in March 2022. The other mutations in this clade have not yet been found elsewhere, and studies are awaited to unravel their role in the life cycle of the virus.

Avoid further spread

Following the identification of the virus, the culling of mink began on October 18, 2022, removing all animals from the farm premises on November 17 of that year. The farm was cleaned with the destruction of all debris and corpses. Most of the 12 farm workers participated in the culling, as they had been in contact with the animals prior to this step. They were tested on the 13th^the and 14^the October by nasopharyngeal swab while asymptomatic, and all tested negative for the virus.

Out of an abundance of caution, they were asked to stay away from people for ten days from last contact with the farm or mink. They also self-monitored for flu-like symptoms. Only one showed symptoms on November 2 but tested negative for the virus.

In particular, mink farm workers have been required to wear face masks since April 2020, when farmed mink were found to be infected with SARS-CoV-2. Later, more protective gear was added, along with washing hands several times a day, while work clothes were washed and showered just as often on the farm. Workers also spent less time off duty on farms, reducing their contact period.

What are the implications?

Mink appears to allow infection with both human and avian influenza viruses. “This species could serve as a potential mixing vessel for interspecies transmission between birds, mammals, and humans..” With reports of H5N1 in birds around the world, care must be taken to prevent infection of mink on farms such as this. It is important to note that, although rare, human infection with avian influenza has a fatal very high 50-60%.

Earlier concerns were raised as mink were found to be susceptible to SARS-CoV-2, with two-way transmission between humans and mink. Such events could cause the spread of similar pathogens to or from wild animals via farmed mink, posing a threat to human health.

This underscores the need for “strengthen the culture of biosafety and bioprotection in this culture system and promote the implementation of ad hoc surveillance programs for influenza A viruses and other zoonotic pathogens at a global level.”