H5N1 influenza virus continues to circulate in cattle (the virus has been found in dairy cows’ milk and has infected farm workers) causing public health officials to consider preparations for a potential outbreak (or even pandemic) in humans. One aspect of pre-pandemic planning is testing currently approved antivirals against influenza A viruses (like H5N1) circulating in peridomestic species.
In a new study, results suggest that in a preclinical model, two FDA-approved flu antivirals 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 are published in Nature Microbiology in the paper, “Baloxavir improves disease outcomes in mice after intranasal or ocular infection with Influenza A virus H5N1-contaminated cow’s milk.”
“Our evidence suggests that it is likely going to be hard to treat people severely infected with this bovine H5N1 bird flu strain,” said 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.”
Though H5N1 infections in people have been rare, there are more than 60 people to date who have become infected from dairy exposures 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 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.”