Is the use of new anti-influenza drugs sustainable or do we risk a drug-resistant pandemic?

Influenza A virus (IAV) is a constant pandemic threat, and antiviral drugs are crucial in pandemic preparedness.

We have shown that anti-influenza drugs neuraminidase inhibitors (NAIs): are not degraded in sewage treatment; can be detected in river water; that low NAI water levels induce resistance in IAVs infecting the natural influenza reservoir, dabbling ducks; that resistance can persist without drug pressure; and that resistant IAVs are not outcompeted by wild-type viruses.

As pandemic IAVs originate in dabbling ducks, imprudent NAI use could lead to a drug-resistant pandemic, a frightening public health scenario. Baloxavir is a new type of IAV antiviral; its use has skyrocketed in Japan. Nothing is known about its environmental fate. Baloxavir could carry the same environmental resistance risks as NAIs.

Thus, we propose a multi-disciplinary project assessing: Baloxavir´s persistence in aquatic environments through 1) development of two analytical methods for baloxavir in water and sediment and 2) experiments on baloxavir´s environmental stability.

The risk for resistance development and persistence in IAVs infecting dabbling ducks exposed to low levels of baloxavir in their aquatic environment by 1) in vivo experiments in Mallards and 2) in vitro competition experiments in embryonated chicken eggs.

Our results will help guide sustainable use of baloxavir during seasonal influenza and in pandemic preparedness already before the drug is widely used globally.