Study shows deadly spread of H5N1 virus from ferrets to feeding kits

Viral RNA titers increased significantly in milk over time and remained high in mammary tissue

During 2020, highly pathogenic avian influenza A(H5N1) viruses of clade 2.3.4.4b emerged and rapidly spread to many parts of Africa, Asia, and Europe. From 2021 to 2022, the 2.3.4.4b clade of H5N1 spread first to North America and then to South America, where it caused large-scale mortality of seabirds. The virus did not spread to marine mammals, except for temporary deaths in pinnipeds and cetaceans in Europe and North America. But things changed when the virus spread to the coasts of Peru and Chile in 2022-2023, infecting and killing 30,000 sea lions. The virus also spread to dolphins, otters, and other marine mammals.

The virus has spread in Argentina, killing more than 17,000 elephant seals, including almost 97% of the population. Until outbreaks occurred in various mammals, H5N1 viruses rarely infected mammals and were thought to be unlikely to spread between mammals.

By the end of March of this year, the virus was first reported in cattle in Texas. The first case of a farm worker in the United States was reported on April 1st.

The patient developed symptoms on March 27, several days after the first case in cattle was reported. This patient had a history of exposure to dairy cows presumed to be infected with the H5N1 virus. As of November 22, 2024, 58 H5N1 cases have been reported in the United States, with the virus spread to 616 dairy herds in 15 states, and 402 dairy herds in California alone.

The 2.3.4.4b clade of H5N1 viruses is typically present in the mammary glands of cows, and the milk of infected cows contains high levels of viral RNA and infectious virus. Viruses that infect the mammary gland have raised concerns about cow's milk as an interface through which the virus can be transmitted to offspring and even humans through breastfeeding. Because studying H5N1 infection in the mammary gland through controlled studies in cows is difficult and labor-intensive, researchers turned to ferrets to study infection and milk-mediated transmission of H5N1 viruses of the 2.3.4.4b clade to the mammary gland. I did. Researchers found that lactating ferrets with mammary gland infections caused by H5N1 influenza virus (2.3.4.4b clade) can spread the infection to their suckling offspring, causing illness. discovered. It also caused 100% mortality in lactating ferrets and baby ferrets. Results have been posted to a preprint server. Preprint has not yet been peer-reviewed.

In another study published in nature On October 28, ferrets infected with H5N1 virus (clade 2.3.4.4b) showed severe disease, with 100% mortality. The study found that the virus spread efficiently between ferrets in direct contact, but not between ferrets through droplets or fomites.

To study H5N1 virus 2.3.4.4b clade transmission from lactating ferrets to infants, researchers in the preprint study inoculated the mammary glands of lactating ferrets with the virus at 2.5 weeks postpartum. . Preprint studies note that viral RNA titers increase significantly in milk over time and remain high in mammary gland tissue. Although there was a significant increase in viral RNA in the oral and nasal cavities in the nursing kits, virus in the nasal cavities of lactating ferrets was delayed and virus present in the oral cavity was minimal. Viral RNA levels in the lungs were lower in lactating ferrets but higher in suckling kits. This indicates that H5N1 2.3.4.4b clade infection in lactating ferrets causes mastitis-associated disease and spread of the virus to suckling pups, resulting in 100% pup mortality. The research paper points out that.

They found that intramammary H5N1 virus (clade 2.3.4.4b) infection resulted in 100% kit mortality in lactating ferrets at 4 days post-inoculation and 6 days post-inoculation. Milk from lactating ferrets showed increased viral RNA levels compared to baseline. “The presence of the virus within the mammary gland suggests active replication of the virus within the mammary gland,” the researchers noted.

significant increase

There was no difference in viral RNA in the oral cavity of lactating ferrets, but there was a significant increase in viral RNA in the oral cavity of nursing kits. RNA levels in the pups' oral cavity peaked four days after vaccination, consistent with viral infection in milk, the researchers wrote. Although lactating ferrets did not show viral RNA in the nasal region even 2 days after inoculation, prolonged contact with the lactation kit increased viral RNA in lactating ferrets.

“Viral dynamics in the oral and nasal cavities suggest that Kit developed a respiratory infection directly from H5N1-positive milk, causing respiratory infection to the mother. These findings suggest that intramammary H5N1 infection “We show that H1N1 causes more severe disease in lactating ferrets and their kits than H1N1,” the researchers wrote.