In the spring of 2022, a few red foxes in Wisconsin were displaying strange behavior. Veterinary pathologist Betsy Elsmo discovered that a local wildlife rehabilitation center was treating foxes with neurological symptoms such as seizures, tremors, and lethargy. Despite testing for common pathogens like canine distemper virus and rabies, the results were negative. However, one red fox kit tested positive for influenza A, a group of viruses that includes seasonal flu strains and those that circulate among birds.
Initially surprised by the diagnosis, Elsmo’s skepticism faded when she came across a study detailing cases of avian influenza in red foxes in the Netherlands. Further examination of the Wisconsin fox kit’s tissues revealed lesions in the brain, lung, and heart that matched those seen in the Netherlands animals. This discovery led to the confirmation of a lethal strain of H5N1 avian influenza in the foxes, which had emerged in Europe in late 2020 and had spread globally by the time infections were detected in Wisconsin.
The ongoing bird flu pandemic has shown that H5N1 can infect a wide range of mammal species, including red foxes. Previously, scientists had only documented bird flu cases in about a dozen mammal species. The ability of H5N1 to infect numerous mammals is due to its widespread distribution among birds, both wild and domesticated, providing more opportunities for mammalian exposure to the virus.
In mammals, bird flu typically manifests as respiratory symptoms, but it can also cause neurological symptoms such as seizures and paralysis if it reaches the brain. Once the virus invades the brain, the infection is often fatal. The current outbreak has confirmed such cases posthumously in various species including house cats, raccoons, sea lions, and dolphins.
H5N1 and related strains have a unique ability to access the brain compared to other flu viruses. The virus can exploit proteins on the surface of cells to gain entry, with some mammalian cells containing proteins that allow for viral replication. This direct entry route to the brain poses a significant threat, especially compared to seasonal influenzas that target cells in the nose, throat, and lungs.
Since 2003, there have been 891 cases of H5N1 in people, half of which were fatal. In the current outbreak, 15 people have been infected, with severe cases resulting in pneumonia and fatalities. While neurological symptoms in humans are rare, the frequency of the virus reaching the brain in other mammals remains unknown due to limited testing.
Furthermore, the pattern of tissue damage caused by H5N1 varies among different mammal species. For example, foxes and raccoons show severe brain lesions, while skunks exhibit fewer brain lesions but more damage to the liver and lymphoid organs. The unusual ability of the virus to affect specific tissues in different species raises questions about its mechanisms of infection.
In some instances, animals infected with H5N1 have shown signs of brain infection without concurrent respiratory symptoms. This phenomenon challenges the conventional understanding of flu viruses as primarily respiratory pathogens. The ability of H5N1 to target the brain directly in certain animals remains a subject of ongoing research to uncover the underlying mechanisms.
The urgency to study the virus in a wider range of mammalian species is crucial to understanding its potential impact and preventing further spread. While the risk to humans remains low, continued vigilance and research are necessary to combat the versatile nature of viruses like H5N1. The ongoing outbreak highlights the adaptability of viruses and the need for comprehensive monitoring to mitigate potential threats to both animal and human health.
