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Current antivirals likely less effective against severe infection caused by bird flu in cows’ milk
Scientists at St. Jude Children’s Research Hospital have found that frequently used antivirals do not work well against the H5N1 avian influenza virus in cows’ milk.
Memphis, Tennessee, March 17, 2025
As the H5N1 avian influenza outbreak continues, scientists are working to better understand the virus’s threat to human health. The virus has been found in dairy cows’ milk and has infected farm workers, prompting scientists at St. Jude Children’s Research Hospital to study potential treatments. Results showed that in a preclinical model, the two most common FDA–approved antivirals for the flu generally work poorly against severe disease caused by the H5N1 virus. Additionally, the researchers found that how someone becomes infected significantly impacts the treatment’s effectiveness. The findings were published today in Nature Microbiology.
“Our evidence suggests that it is likely going to be hard to treat people severely infected with this H5N1 bird flu strain,” said corresponding author Richard Webby, PhD, St. Jude Department of Host-Microbe Interactions. “Instead, reducing infection risk by not drinking raw milk and reducing dairy farm workers’ exposures, for example, may be the most effective interventions.”
Inadequate antivirals
Though H5N1 infections in people are rare, there are over 60 people who have become infected to date. Some were infected through exposure to contaminated raw cows’ milk, such as dairy workers infected through splashes or aerosolized particles reaching their noses or eyes. Given the real risks to human health, the scientists used a mouse model to test how each antiviral drug worked against the virus when it was obtained through three different exposure routes.
“In general, baloxavir [Xofluza] caused a greater reduction in viral levels than oseltamivir [Tamiflu], but neither were always effective,” said first author Jeremy Jones, PhD, St. Jude Department of Host-Microbe Interactions.
The researchers studied exposure routes that included the eye, mouth and nose, which are the most plausible ways to become infected with the virus. The oral route, which mimics drinking raw infected cow’s milk, caused the worst infections that were also hardest to treat.
“The virus spread far beyond its normal infection of the lungs,” Webby said. “It expanded to the brain and the bloodstream, and the antivirals failed to stop it or improve survival outcomes.”
In contrast, findings showed that baloxavir controlled infections through the eye fairly well. These results are particularly relevant as the ocular route appears to be the common infection pathway for people who work directly with dairy cows, from splashes or aerosolized particles.
“Baloxavir conveyed 100% survival compared to 25% with oseltamivir,” Jones said. “So, we are seeing enhanced benefits from baloxavir for the ocular infection route.”
Results were mixed for the nasal route. Baloxavir reduced viral levels better than oseltamivir, but the virus still reached the brain. Both antivirals increased survival, with baloxavir and oseltamivir achieving a 75% and 50% survival rate, respectively, but neither was completely effective.
“We showed our existing antivirals’ effectiveness against H5N1 bird flu is route and drug dependent, in some cases doing almost nothing,” Webby said. “Therefore, while we explore different drug combinations and doses, we need to do anything we can to reduce the risk of infection, as that is the best way to protect people from this virus right now.”
Authors and funding
The study’s other authors are Konstantin Andreev, Thomas Fabrizio and Elena Govorkova, all of St. Jude and Andrew Bowman, The Ohio State University.
The study was supported by grants from the National Institute of Allergy and Infectious Diseases (contract#75N93021C00016) and ALSAC, the fundraising and awareness organization of St. Jude.
Read the full text of the article at Nature Microbiology:
Baloxavir improves disease outcomes in mice after intranasal or ocular infection with Influenza A virus H5N1-contaminated cow's milk
...
https://www.stjude.org/media-resour...nfection-caused-by-bird-flu-in-cows-milk.html
-------------------------------------------------
Testing approved antivirals against A(H5N1) influenza viruses circulating in peridomestic species, including dairy cows, is critical to public health and pre-pandemic planning. It cannot be tested in humans due to A(H5N1) disease severity. Here, in mice, we demonstrate that US FDA-approved baloxavir treatment mediates improved disease outcomes (survival and viral dissemination) over oseltamivir after lethal intranasal and ocular challenge with A(H5N1)-contaminated cow milk.
...
(Paywall)
https://www.nature.com/articles/s41564-025-01961-5
Scientists at St. Jude Children’s Research Hospital have found that frequently used antivirals do not work well against the H5N1 avian influenza virus in cows’ milk.
Memphis, Tennessee, March 17, 2025
As the H5N1 avian influenza outbreak continues, scientists are working to better understand the virus’s threat to human health. The virus has been found in dairy cows’ milk and has infected farm workers, prompting scientists at St. Jude Children’s Research Hospital to study potential treatments. Results showed that in a preclinical model, the two most common FDA–approved antivirals for the flu generally work poorly against severe disease caused by the H5N1 virus. Additionally, the researchers found that how someone becomes infected significantly impacts the treatment’s effectiveness. The findings were published today in Nature Microbiology.
“Our evidence suggests that it is likely going to be hard to treat people severely infected with this H5N1 bird flu strain,” said corresponding author Richard Webby, PhD, St. Jude Department of Host-Microbe Interactions. “Instead, reducing infection risk by not drinking raw milk and reducing dairy farm workers’ exposures, for example, may be the most effective interventions.”
Inadequate antivirals
Though H5N1 infections in people are rare, there are over 60 people who have become infected to date. Some were infected through exposure to contaminated raw cows’ milk, such as dairy workers infected through splashes or aerosolized particles reaching their noses or eyes. Given the real risks to human health, the scientists used a mouse model to test how each antiviral drug worked against the virus when it was obtained through three different exposure routes.
“In general, baloxavir [Xofluza] caused a greater reduction in viral levels than oseltamivir [Tamiflu], but neither were always effective,” said first author Jeremy Jones, PhD, St. Jude Department of Host-Microbe Interactions.
The researchers studied exposure routes that included the eye, mouth and nose, which are the most plausible ways to become infected with the virus. The oral route, which mimics drinking raw infected cow’s milk, caused the worst infections that were also hardest to treat.
“The virus spread far beyond its normal infection of the lungs,” Webby said. “It expanded to the brain and the bloodstream, and the antivirals failed to stop it or improve survival outcomes.”
In contrast, findings showed that baloxavir controlled infections through the eye fairly well. These results are particularly relevant as the ocular route appears to be the common infection pathway for people who work directly with dairy cows, from splashes or aerosolized particles.
“Baloxavir conveyed 100% survival compared to 25% with oseltamivir,” Jones said. “So, we are seeing enhanced benefits from baloxavir for the ocular infection route.”
Results were mixed for the nasal route. Baloxavir reduced viral levels better than oseltamivir, but the virus still reached the brain. Both antivirals increased survival, with baloxavir and oseltamivir achieving a 75% and 50% survival rate, respectively, but neither was completely effective.
“We showed our existing antivirals’ effectiveness against H5N1 bird flu is route and drug dependent, in some cases doing almost nothing,” Webby said. “Therefore, while we explore different drug combinations and doses, we need to do anything we can to reduce the risk of infection, as that is the best way to protect people from this virus right now.”
Authors and funding
The study’s other authors are Konstantin Andreev, Thomas Fabrizio and Elena Govorkova, all of St. Jude and Andrew Bowman, The Ohio State University.
The study was supported by grants from the National Institute of Allergy and Infectious Diseases (contract#75N93021C00016) and ALSAC, the fundraising and awareness organization of St. Jude.
Read the full text of the article at Nature Microbiology:
Baloxavir improves disease outcomes in mice after intranasal or ocular infection with Influenza A virus H5N1-contaminated cow's milk
...
https://www.stjude.org/media-resour...nfection-caused-by-bird-flu-in-cows-milk.html
-------------------------------------------------
- Brief Communication
- Published: 17 March 2025
- Jeremy C. Jones,
- Konstantin Andreev,
- Thomas P. Fabrizio,
- Andrew S. Bowman,
- Elena A. Govorkova &
- Richard J. Webby
Testing approved antivirals against A(H5N1) influenza viruses circulating in peridomestic species, including dairy cows, is critical to public health and pre-pandemic planning. It cannot be tested in humans due to A(H5N1) disease severity. Here, in mice, we demonstrate that US FDA-approved baloxavir treatment mediates improved disease outcomes (survival and viral dissemination) over oseltamivir after lethal intranasal and ocular challenge with A(H5N1)-contaminated cow milk.
...
(Paywall)
https://www.nature.com/articles/s41564-025-01961-5