St. Jude Researchers: Current Antivirals Likely Less Effective Against Severe Infection Caused by Bird Flu in Cows’ Milk

 

Credit NIAID

#18,378

During the opening months of any influenza pandemic, a well-matched and abundant flu vaccine will not be readily available, leaving antiviral drugs (Oseltamivir & Baloxavir) as the primary pharmaceutical treatment in our armamentarium.  

Of the two, Oseltamivir (aka `Tamiflu') is the least expensive and most widely available.  While neither are a `cure', both have been shown to reduce the duration of severe influenza infection, and are linked to better outcomes. 

Both, however, are susceptible to mutations within the flu virus which can decrease their effectiveness. While most often these are reported as `spontaneous mutations' that occur in about 1% of patients receiving treatment, it is also possible for `wild-type' flu viruses to develop resistance. 

Last month, in - in Emerg. Microbes & Inf: Oseltamivir Resistant H5N1 (Genotype D1.1) found On 8 Canadian Poultry Farms - we saw a report on a large outbreak of Oseltamivir resistant H5N1 which emerged over several weeks last fall.

This resistance was due to an H275Y mutation in the NA gene, which also turned up in 2007-2008 in seasonal H1N1 (see CIDRAP article With H1N1 resistance, CDC changes advice on flu drugs).

While we've not seen any reports of H275Y in D1.1 samples collected in the United States, last November the CDC did report finding a far-less impactful mutation (NA-S247N) in 3 poultry workers from Washington State, which they stated may slightly reduce the virus's susceptibility to antivirals.

Yesterday the Journal Nature published a report from researchers at St. Jude Children's Research Hospital which find the Bovine (B3.13 genotype) virus is less susceptible (in mice) to current antivirals.    

This study is behind a paywall, but St. Jude has published an accompanying news release.   

Baloxavir improves disease outcomes in mice after intranasal or ocular infection with Influenza A virus H5N1-contaminated cow’s milk

Jeremy C. Jones, Konstantin Andreev, Thomas P. Fabrizio, Andrew S. Bowman, Elena A. Govorkova & Richard J. Webby Nature Microbiology (2025) Cite this article

Abstract

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.

Below you'll find some excerpts from the new release. Follow the link to read it in its entirety.

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

 

Our evidence suggests that it is likely going to be hard to treat people severely infected with this bovine 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.”

“In general, baloxavir [Xofluza] caused a greater reduction in viral levels than oseltamivir [Tamiflu], but neither was always effective,” said first author Jeremy Jones, PhD, St. Jude Department of Host-Microbe Interactions.

“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.”

         (Continue . . . )

While it is far from guaranteed that the bovine (B3.13) genotype (or an offshoot) will become a pandemic strain - and the results obtained from mice experiments may not match human experience - antivirals are unlikely to be a panacea for a pandemic. 

• First, while millions of courses are stockpiled, there isn't near enough to treat everyone during a pandemic. And in the past, we've seen recommendations for `double the dose, for double the time' when treating H5N1.

• And even during moderately severe flu seasons, we've seen difficulties getting antivirals  to patients who need them in the crucial first 48 hours of infection (see CDC HAN #0482: Prioritizing Antiviral Treatment of Influenza in the Setting of Reduced Availability of Oseltamivir).

• And, as we saw in 2008, widespread antiviral resistance can sometimes develop quickly. 

Although there may be other treatments developed in the opening months of a pandemic (mAbs, convalescent serum, etc.), our first line of defense in the next pandemic will - once again - rely heavily on NPIs (non-pharmaceutical interventions),

Things like face masks, hand washing, ventilation, staying home while sick, and avoiding crowds.

Which is why I'm recommending that people consider now (see A Personal Pre-Pandemic Plan) what they will do when the next global health crises emerges.