Beyond the Barnyard: How H5N1 Is Crossing Species—and Borders

During the August 2025 Health Watch USA(sm) webinar entitled “Combating Infectious Disease Challenges,” several lectures were devoted to the then-outdated topic of H5N1 or the bird flu. Many people in the public, including those on social media, attributed the disappearance of the bird flu over the summer months to the implementation of effective suppression strategies. A past threat that was now long gone.

I am afraid what we observed was just the normal disappearance of influenza during the summer months, as we have seen with the seasonal flu for decades.

On October 24th, Reuters reported bird flu outbreaks in several European countries that are at the highest level in decades, raising fears of renewed culling of millions of birds. Countries, along with the World Health Organization (WHO), are monitoring the situation. France is taking action by beginning its third annual bird flu vaccination campaign, starting with farm ducks, and Belgium has isolated poultry flocks.

In the US, Bird flu has returned with the deaths of nearly 7 million farmed birds since September. This includes 1.3 million turkeys, which threatens our supply just before Thanksgiving. And three states have experienced new outbreaks in dairy cattle.

Richard Webby, PhD, Director of the WHO Collaborating Centre for Studies on the Ecology of Influenza in Animals and Birds; and Cynda Crawford, DVM, PhD, Fredrica Saltzman Endowed Professorship Chair in Shelter Medicine at the University of Florida, presented on what we have learned and know about the bird flu. It is hoped that the following summary of this information will help us prepare for and confront the challenges that will almost assuredly be posed by H5N1 in the months and years to come.

First, the name “Bird Flu” is a misnomer. All influenza strains, whether human seasonal flu or swine flu, originate in birds. At any given time, approximately 15% of wild birds can be infected with an avian flu strain.Only a small percentage of these will become sick, and only a small percentage of viruses will jump to other species. Usually, when a human becomes infected, it is through an intermediate host, such as a pig with the “swine flu”.Thus, it is best to refer to these viruses based on their hemagglutinin and neuraminidase structures.For the “Bird Flu,” we will be discussing the H5N1 virus.
 
Infections in Birds: Before 2021, North America had been relatively free of H5N1. The virus then developed the ability to spread extensively through migratory birds and reentered North America in 2021 to 2022. By 2025, the H5N1 virus had infected poultry in all 50 states, necessitating the depopulation of over 175 million birds. The states of California, South Dakota, and Minnesota have been hit especially hard. Chickens are highly susceptible to the virus and develop severe pneumonia, with rapid mortality over hours rather than days. It is considered most humane to depopulate the flocks.

Infections in Mammals: The current H5N1 strain has an increased ability to infect mammals, mainly through the predatory consumption of infected birds. To date, well over 200 different mammalian species have been infected, with spread to mammals all too common in the United States. Even mammals once thought to be immune to the virus, such as seals and porpoises, have become infected. However, there has been limited mammal-to-mammal transmission.

The appearance of H5N1 clade 2.3.4.4b was associated with mammalian infections. This new clade not only binds to the avian alpha-2,3 sialic acid receptor, but rare binding to the alpha-2-6 receptor found on mammalian cells has been reported. Many mammalian species have a mixture of these two receptors in their respiratory tract.
 
Infections in Dairy Cattle: Dairy barns are open to the outside, exposing cattle to migratory birds. Cows were not considered susceptible to avian influenza, but as the H5N1 virus continued to mutate and form clades B3.13 and D1.1, dairy cattle became very susceptible. In dairy cattle, the virus does not appear to be transmitted through respiration, but through the milk. This is because the cow’s udder has viral receptors closer to those found in birds than to those in the human respiratory tract.

In cows, the clinical manifestation of infection is mastitis rather than pneumonia. There is a significant drop in milk production, and the milk contains high viral loads, with a creamy yellow appearance. Infection is usually not fatal. The virus is spread by movement of infected cows, contaminated milking equipment, and through milk spillage. The virus can also become airborne when milking equipment is changed, leading to worker infections.

Infections in Domestic Cats: Cats are very susceptible to H5N1. Most cats become infected by ingesting infected bird carcasses, and on dairy farms by ingesting infected milk. Ingestion of raw milk is an example of mammal-to-mammal transmission. Cat infections have increased with clade 2.3.4.4b, and unlike dairy cows, infected cats develop a severe, highly fatal neurological disease. The clinical signs are similar to rabies. Infected cats have a fatality rate of up to 67% with the median time of symptom onset to death of only 2 days. There is no evidence of cat-to-human transmission.

Cats at highest risk for bird flu are those with outdoor access, and those who live on dairy or poultry farms. A new transmission route, which even affects indoor-only cats, is the acquisition of raw milk or raw cat food made with chicken from commercial vendors.

Infections in Humans: H5N1 is not well adapted to infect humans. The virus binds to slightly different sugar receptors than those that are commonly found in humans. Human H5N1 infections tend not to be respiratory but mainly conjunctivitis, presumably from milk splashing or chicken dander getting into farm workers’ eyes. Unlike human lungs, human eyes have abundant receptors that avian flu viruses like to bind to. Thus, most human cases are mild. To date, there has not been sustained human-to-human transmission.
 
Human fatalities can occur, but the previous high rates of fatalities in humans may be related to healthcare workers being exposed to very high viral doses and to the underreporting of mild cases.

H5N1 has had sporadic mutations that would facilitate human transmission, but outbreaks of these viruses have burned out.If H5N1 takes hold in the swine population, adaptation to humans would be facilitated, since pigs are an efficient intermediate host for human infections.

Control of Spread: There are limited strategies to stop the transmission of the H5N1 virus, since it resides in migratory birds, which are impossible to control. Carcasses can still be removed, and local domesticated species can still be protected. Improving biosecurity and culling of farm birds can help protect both the farm industry and human farm workers. The culling of chickens is necessary because of the infection’s extremely high mortality rate, the need to protect farm workers, and to prevent the virus from increasing its ability to infect humans.

There is evidence that vaccination can protect both the farm animals and human health. However, in the US, H5N1 vaccination is not routinely administered to poultry due to trade agreements with other nations. It is challenging to export vaccinated poultry. H5N1 vaccines are not approved for use in farm animals in the United States.
 
However, at least 20 H5N1 vaccines have been licensed worldwide, and at least 32,000 individuals have been vaccinated. In addition, mRNA technology can rapidly bring a clade-specific H5N1 vaccine to market. Unfortunately, this virus is only a few mutations away from developing effective human-to-human transmission.We need to be prepared for this eventuality and have an effective plan to combat this infectious disease challenge when it happens.