Bhadelia is an infectious diseases physician and associate professor.
The outbreak of highly pathogenic avian influenza A (HPAI) (H5N1) in dairy herds across the U.S. appears to be expanding, with over two dozen farms being affected in eight states. Although only one mild human case in a dairy farmer in Texas has been reported during the current outbreak, the situation is raising concerns for several reasons: it’s happening against a steady, worrisome background of viral evolution and it sets up the potential for increased exposure among humans as well as a possible impact on our food sources.
A Worrying Trend of H5N1 in Mammals
This outbreak marks the first documented instance of H5N1 infection in dairy cows, highlighting a worrying trend that has been occurring over the last 2 years where the virus has moved from infecting birds to a growing range of mammals. More than 40 new mammalian species have been affected, and more than 26 countries have reported infections in mammals during the current zoonotic wave (2021-2024) compared to 10 countries prior to 2019. This represents an increase in both the geographic and host range of the virus.
The individual outbreaks have also been deadly, affecting large numbers of birds and animals. For example, last spring the virus killed over 5,000 sea lions on the coast of Peru, along with more than 100,000 birds. The year prior to that, a smaller outbreak hit New England Harbor seals, where seal-to-seal transmission was suspected. The CDC reports that nearly 86 million wild aquatic birds, commercial poultry, and backyard or hobbyist flocks in 48 states have been infected in the U.S. beginning in January 2022. The increased infections in birds have created more opportunities for spillover events — instances where the virus jumps from a bird host to a mammal.
This dramatic increase in the number of susceptible mammalian hosts suggests the virus’s ability to adapt to diverse physiologies, potentially paving the way for its eventual adaptation to humans. The more animal species and more individual animal numbers (infection burden) the virus infects, the greater the opportunity it has to undergo mutations. These mutations could potentially enable the virus to overcome the barriers that currently prevent efficient and sustained human-to-human transmission.
This is why any reports of potential mammal-to-mammal transmission raise further concern for continued adaptive evolution, as was suspected among New England seals, as well as during an outbreak on a mink farm in Spain last year. A recent Science article reports that the U.S. Department of Agriculture (USDA) suspects that the current transmission between dairy cows is occurring through contaminated milking equipment.
H5N1 Cases in Humans To Date
Between 2003 and April 2024, a total of 889 cases and 463 deaths have been reported in 23 countries. The recent human case related to the dairy herd outbreaks represents only the second human case detected in the U.S. (the previous one was in 2022 in Colorado), but it is the first time the H5N1 subtype has been shown to be transmitted between a mammal and a human being.
The affected individual reportedly had contact with infected cows and suffered conjunctivitis; he then isolated and was given antiviral treatment. The specific H5N1 strain (HA clade 2.3.4.4b) identified in the U.S. mammalian outbreaks harbors mutations (PB2-E627K and PB2-D701N) that facilitate viral replication in mammalian hosts. Thankfully, the genetic analysis of virus from the human case in Texas showed only one change (PB2-E627K), which has been detected in other human and mammalian infections with H5N1, and no further genetic changes. This means the risk to general human population remains low.
However, when an increased number of domesticated species like cows (or other species like cats, which have been reported to be sporadically infected) are infected, it raises the risk for continued human exposure to the virus, creating a runway to further evolution. Even without the mammal-to-human transmission, the potential threat of H5N1 to human health is further amplified by the various transmission routes, including through fomites (contaminated surfaces and objects) to workers on farms with ongoing outbreaks.
The Importance of Heightened Infection Control
This underscores the crucial role of implementing effective infection control measures during outbreaks to minimize the risk of spillover events. USDA and state officials have outlined biosecurity practices — such as limiting who enters farms — to help curb some of this risk, but there are currently no quarantines in place or restrictions on movements of herds. The situation also necessitates providing greater occupational health support to workers on the affected farms.
More broadly, as H5N1 is being detected among birds in highly populated areas, it is a good reminder to keep a distance from sick or dead birds or other animals, particularly when it comes to pets and children. Despite the mildness of the Texas case, there are also other reasons to prevent human infections, including the possibility of the virus eventually finding a person who is medically vulnerable or immunocompromised and who may have a more severe clinical course. Additionally, if human cases start to ramp up considerably, it may be challenging to meet the demand for prophylactic vaccination with our currently stockpiled vaccines.
In addition, because the outbreaks are affecting dairy cows, there is rightfully concern of transmission of infection, particularly via raw milk or other products like cheese from raw milk. For now, FDA reports there is no threat to the food supply. However, the situation should be closely monitored.
Toward a Better Understanding of the Risks
In brief, the current risk of H5N1 virus is best understood as being due to more species infected — more infections in more places that are closer to human populations. To further elaborate on the risk, we need a clearer understanding of how infections are being transmitted between species. We can ascertain this through greater testing of animals and humans on farms with outbreaks, coupled with phylogenetic analyses of the viruses from the individual infections to trace transmission. We also need a better understanding of the natural history of this infection in infected animals and humans.
It appears that the testing is currently being limited to symptomatic cows and in reported symptomatic human infections. In my opinion, assuming too early that we know all the types of symptomatic presentations of an evolving virus has been detrimental in establishing the true epidemiology during past epidemics.
The case fatality rate of newly discovered infectious diseases in humans tends to appear high because only the sickest patients seek care and are tested and detected. In 2014-2015, my own clinical experience in caring for Ebola patients in West Africa instructed me that even diseases known to have high mortality can have many individuals who have much milder presentations, as studies have shown since then. In 2020, we made early assumptions about the presentations and transmission of COVID-19 that were too narrow, costing us an edge in early detection of the scope of the pandemic in the U.S.
These lessons teach us that to get a better sense of the current situation across species, a wider testing net needs to be cast among animals and humans with potential high risk exposures within the outbreak areas. This should include those who may not have symptomatic disease, or those with symptoms not typically described with H5N1.
There may be economic, social, and political barriers to expanding such testing, which need to be weighed against the costs of a larger outbreak. Surveillance could also be expanded by increasing the number of human influenza samples that are PCR-positive being genotyped weekly at public health laboratories to detect possible sporadic human cases of H5N1 in areas with large animal outbreaks.
Continued research into the evolving nature and presentation of H5N1 — as well as the effectiveness of our current medical countermeasures, such as vaccines, coupled with other robust public health measures — remains crucial in mitigating the risk of zoonotic transmission to humans. A true public health success would be to stop the virus from adapting to humans in the first place, rather than waiting for it to evolve to become a threat.
Now is also the time to further invest in ensuring we have the capacity to scale up vaccines, diagnostics, and antiviral production, and that we can quickly deliver in case of a larger human outbreak. All of these actions require adequate funding, proactive planning, multistakeholder involvement, and greater global collaboration between animal and human health experts.
Nahid Bhadelia, MD, MALD, is the founding director of Boston University (BU) Center on Emerging Infectious Diseases. She is also an infectious diseases physician and an associate professor at the BU School of Medicine. She previously served as the senior policy advisor for Global COVID-19 Response on the White House COVID-19 Response team.
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