Infectious Diseases 2025

Highly pathogenic avian influenza (HPAI) H5N1 has spread rapidly across the Americas since 2021, causing unprecedented mortality in wild birds and marine mammals. Yet, human deaths remain far fewer than in previous H5N1 outbreaks. Understanding why is vital for assessing future pandemic risks.
Recent research points to three possible explanations:
- Molecular factors: Current H5N1 strains in the Americas retain high-pathogenicity markers but lack some mammalian-adaptive mutations, making them somewhat less virulent in humans.
- Epidemiological factors: Many infections may go undetected. Serological surveys in U.S. farmworkers and veterinarians suggest a much lower infection fatality rate (~0.1%) than earlier WHO estimates.
- Immunological factors: Widespread exposure to seasonal H1N1 flu since 2009 may provide partial cross-immunity through shared neuraminidase proteins, reducing disease severity.
At the same time, high mortality in mammals such as sea lions and mink likely results from very high infectious doses acquired through scavenging infected birds, not necessarily from greater viral virulence.
Human mortality in the current H5N1 epidemic is likely reduced by a combination of viral genetics, undercounted infections, and partial immunity from prior flu exposure. However, the virus continues to evolve and adapt to new hosts. Even with a relatively low infection fatality rate, a large-scale outbreak could have major global consequences.