Current antivirals not successful in treating severe H5N1 bird flu infections

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, two FDA–approved flu antivirals generally did not successfully treat severe H5N1 infections. Additionally, the researchers found that the route of infection, whether through the eye, the nose or the mouth, significantly impacts a 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 bovine H5N1 bird flu strain. Instead, reducing infection risk by not drinking raw milk and reducing dairy farm workers' exposures, for example, may be the most effective interventions."

Richard Webby, PhD, corresponding author, St. Jude Department of Host-Microbe Interactions

Inadequate antivirals

Though H5N1 infections in people are rare, there are more than 60 people who have become infected from dairy exposures to date in the current outbreak. Some were infected through exposure to contaminated raw cows' milk, such as dairy workers who were infected through splashes or aerosolized particles reaching their noses or eyes. Given the 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 was 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 common ways to become infected with the virus. The oral route, which mimics drinking raw infected cow's milk, caused the worst infections that were hardest to treat.

"The virus spread orally 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.

"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.

"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."