Credit EID Journal
#19,175
Nearly a year ago (June 2025) we looked at a Preprint: Dairy Cows Infected with Influenza A(H5N1) Reveals Low Infectious Dose and Transmission Barriers that suggested that the popular belief about how HPAI H5 was transmitting between dairy cows was either flawed, or at least incomplete.The initial assumption by the USDA had been that the B3.13 genotype entered dairy cattle via a single spillover from birds - in the spring of 2024 in Texas - and was then spread to other states by the interstate transport of infected cattle.
This spillover was treated more-or-less as a fluke, since cattle were not considered particularly susceptible to influenza infection. The B3.13 genotype was somehow unique, and the threat of seeing additional spillovers was deemed low.
Cow-to-cow transmission within these herds was quickly hypothesized to be due to contaminated milking machines, although other routes of infection could not be ruled out (see EID Journal: Persistence of Influenza H5N1 and H1N1 Viruses in Unpasteurized Milk on Milking Unit Surfaces).
But cracks in these assumptions were starting to appear.
- In May of 2024, we learned that the USDA had detected H5N1 In Alpacas (B3.13), which had apparently spilled over from poultry.
- By July, Germany's FLI demonstrated that European H5 genotypes could also infect cattle
- In August we saw a Preprint: Highly Pathogenic Avian Influenza H5 Virus Exposure in Goats and Sheep (in Pakistan)
- In early 2025, the `single spillover' theory took another hit when a 2nd, and then a 3rd, spillover of a new (D1.1) genotype occurred in Nevada and Arizona.
- And in March of 2025, we saw a study (see Virology: Detection of Antibodies Against Influenza A Viruses in Cattle) which reported that bulls and steers were just as likely to carry antibodies to (non-HPAI H5) IAV as cows and heifers
Last summer's preprint raised additional concerns, because they were unable to duplicate the suspected transmission of HPAI by contaminated milking machines under laboratory conditions.
In this study, we demonstrate that a low dose of virus is sufficient to establish robust intramammary infection, which may underlie the widespread and efficient transmission of influenza A(H5N1) in dairy herds.
However, sentinel cows repeatedly exposed to contaminated milking equipment and cohoused with infected cows did not become infected, indicating that cow-to-cow transmission observed on dairy farms may depend on factors that are not easily replicated under experimental conditions in high biocontainment research settings.
Since then we've seen the size and scope of HPAI H5 in cattle, ruminants, and other mammals continue to expand, with reports from both North America and Europe.
EID Journal: Highly Pathogenic Avian Influenza A(H5N1) Virus RNA in Bovine Semen, California, USA, 2024
While the number of new herds reported infected in the United States has dropped dramatically, testing remains both narrow in scope and limited, and the full extent of HPAI's spread is likely unknown.
All of which brings us to an update to last year's preprint, now in press for Nature Communications, which finds (a year later) that many questions regarding the transmission of HPAI in dairy cattle remain unanswered.
The full report is very much worth reading. I've only posted some highlights below, so follow the link. I'll have a bit more after the break.
Dairy cows infected with influenza A(H5N1) reveals low infectious dose and transmission barriers
Carolyn Lee, Natalie N. Tarbuck, Hannah J. Cochran, Bryant M. Foreman, Patricia Boley, Saroj Khatiwada, Alok Dhakal, Khadijat O. Adefaye, Jennifer Schrock, Mohammad Jawad Jahid, Thamonpan Laocharoensuk, Raksha Suresh, Olaitan Shekoni, Erika Stevens, Sara Dolatyabi, Christina Sanders, Elizabeth Ohl, Devra Huey, Juliette Hanson, Kara Corps, Renukaradhya Gourapura, Richard J. Webby, Cody J. Warren, Scott P. Kenney & Andrew S. Bowman
ABSTRACT
Highly pathogenic avian influenza A(H5N1) virus exhibits a strong tropism for the bovine mammary gland, challenging our understanding of influenza A virus host range and tissue specificity.We performed experimental studies with an influenza A(H5N1) B3.13 genotype virus in female lactating dairy cattle to define the infectious dose, routes of exposure, and factors linked to morbidity and mortality. Here, we demonstrate that intramammary inoculation with as few as 10 TCID50 establishes a robust infection and shedding of high -titer virus in milk .Despite this low infectious dose, H5N1 does not readily transmit via contaminated milking equipment and close contact with infected animals. High - dose intramammary exposure results in severe disease and mortality, while respiratory and oral exposure s are less likely to establish productive infection and associated morbidity.This study challenges current hypotheses of H5N1 transmission on dairy farms, raising important questions about potential agent, host, or environmental cofactors contributing to viral spread .
While the mammary gland appears to be a primary site of viral replication in dairy cows, the initial route of transmission from wild birds remains unclear. This uncertainty, along with the potential for respiratory exposure in milking parlors19,28, prompted our investigation of intranasal inoculation as a possible route of infection.The macroscopic lesions observed in the respiratory tract suggest that influenza A(H5N1) B3.13 genotype can cause subclinical pathology in bovine respiratory tissues. However, the absence of clinical disease ( e.g. , fever, decreased milk production , and feed intake) , or virus present in milk at any time point indicates that this route of infection likely does not contribute to systemic disease and introduction into mammary tissue.Additionally, chickens co -housed in open air cages adjacent to intranasally inoculated cows did not become infected as evidenced by lack of viral nucleic acid in swabs and overt disease despite salivary contact between an inoculated cow and chicken feed. We attribute this lack of transmission to multiple factors including limited viral shedding from nasal secretions and potentially high number of air changes (i.e., BSL - 3 engineering controls) in animal holding rooms.Although human -to -human transmission of influenza A(H5N1) virus has not been reported, the persistence of the virus in dairy cattle and evidence of mammalian adaptation10, coupled with the broad and unprecedented host range, are alarming from a public health perspective.A second, separate introduction of the D1.1 genotype virus, primarily circulating in wild birds, was reported in dairy cows in early 2025. Unlike the B3.13 virus circulating in cattle, this D1.1 genotype has been associated with severe disease in humans, resulting in two deaths 31 –33 —a highly concerning feature should this genotype continue to spread unfettered.Further, the co -circulation of B3.13 and D1.1 viruses in dairy cows increases the risk of reassortment and viral evolution and complicates efforts to control the influenza A(H5N1) outbreak. Additional studies are needed to characterize the immune response and assess the level of protection following re -exposure to both homologous and heterologous influenza A(H5N1 ) viruses.
The mechanism of transmission within and between dairy herds is a critical question that remains and urgently needs to be answered.
While I would love to be able to point to a single individual, agency, or special interest group that I believe to be the bottleneck for this investigation, the reality is this is a complex, highly unusual outbreak, dispersed over > 1000 locations across the nation.
Cattle are often asymptomatic, and infections tend to be transient, making the testing of individual cows impractical. Lactating cattle are more easily tested (via bulk milk sampling), and so that's where the virus has mostly been identified.
We're HPAI H5 in dairy cows perceived as being a much greater public health threat, I suspect we might be further along. But thus far, its impact on public health has been minimal. Of course, that could change.
Complicating matters, the answer to transmission on the farm is likely multifocal.
Despite the above findings, contaminated milking equipment may still play some part in HPAI transmission, as well as management of farm waste (manure), waste water runoffs, contaminated `milk disposal' practices, `aerosolization' in milking parlors, rodents and other peridomestic animals, and perhaps even flies or other insects.
PLos Bio: Surveillance on California dairy farms reveals multiple possible sources of H5N1 influenza virus transmission
We've been lucky in that HPAI H5N1 has yet to figure out how to transmit efficiently in humans, and at least in the United States, has been relatively mild in people. And it is even possible that cattle will prove to be a dead-end host for the virus.
But none of this is guaranteed.
If and when the next pandemic virus emerges the one thing we won't have in any abundance is time. Which makes anything we can do today to better understand the threats before us - and how to combat them - a wise investment for our future.
