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Will mink-to-mink H5N1 flu on a farm in Spain spread ferret-to-ferret in a lab?

Daniel R. Lucey, MD, MPH, FIDSA
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Last week, Aguero et al. reported in the journal Eurosurveillance that in October 2022, H5N1 avian influenza (clade 2.3.4.4b) caused mink-to-mink infections and some deaths (peak of 4.3%) on a farm with more than 51,000 mink in Galicia in northwest Spain. Although H5N1 “avian flu” has infected limited numbers of mammalian species, this is the first reported outbreak of large-scale transmission between mammals of this highly pathogenic avian influenza. Tests for SARS-CoV-2 were negative unlike in the past on other mink farms in Europe and the USA.

A detailed investigation was done of the epidemiologic, clinical and genetic aspects of this outbreak by the co-authors from Spain and researchers from Italy. All the 11 farm workers who had contact with the mink and were involved in the culling activities (completed by Nov. 17) had nasopharyngeal swabs taken Oct. 13-14 that “tested negative for avian influenza.” On Nov. 2, “one of the farm workers had a runny nose,” and RT-PCR was performed on a nasopharyngeal sample, which was negative.

A minor point is that no mention was found (by this reader) of acute and convalescent antibody tests (as was done for poultry farm workers during the H5N8 outbreak in Russia in 2020) or of obtaining oropharyngeal swabs to test for virus.

Of note, face masks for all farm workers on mink farms in Spain were made compulsory in April 2020, when SARS-CoV-2 infection of mink farms in the Netherlands was first identified. (The 2020 outbreak of SARS-CoV-2 in farmed mink in Spain was in the eastern part of the country, far from Galicia in northwest Spain.)

Genetic sequencing of the H5N1 viruses detected at the mink farm in Galicia in October 2022 “are distinguished from all the clade 2.3.4.4b viruses characterized so far in the avian population in Europe as they bear an uncommon mutation (T271A) in the PB2 gene … the same mutation is in the avian-like PB2 gene of the 2009 pandemic swine-origin influenza A (H1N1) virus,” according to the Eurosurveillance report.

Lastly, controversial experiments in 2012 by Dutch and U.S. laboratory researchers infected ferrets in the laboratory with genetically modified earlier clades of H5N1 (originally from Indonesia and Vietnam) and then performed serial passages in 10 sets of ferrets. The result in both cases was an airborne mammal-to-mammal (ferret-to-ferret or “F2F”) transmissible H5N1 avian flu virus.

It would not be surprising if somewhere in the world testing of this 2022 mink-to-mink transmissible H5N1 avian flu virus (or a modified version) is performed in the laboratory to see if it is transmitted from ferret-to-ferret either by direct contact and/or via respiratory droplets without direct contact.

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