Credit EID Journal
#18,763
In the 15 months since dairy cattle were first reported to be infected with HPAI H5N1 in Texas, the USDA has confirmed 1,073 infected herds across 17 states, although limited testing and a focus almost solely on lactating dairy cows suggests the impact may be higher (see Nature: A Mathematical Model of H5N1 Influenza Transmission in US Dairy Cattle).
The assumption by the USDA has long 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.
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).
Over the past year we've also seen sporadic spillovers of H5N1 into goats, alpacas, pigs, and most recently to sheep in both the UK and in Norway. Despite very limited surveillance, hundreds of peridomestic animals (cats, foxes, mice, etc.) have been infected in and around dairy farms and in the wild.
Complicating matters further, last February, two states (Nevada & Arizona) reported dairy herds infected with a new H5N1 genotype (see APHIS Statement On HPAI Genotype D.1 In Arizona Dairy Cattle).
APHIS described this as a `third spillover' and that it `. . . may indicate an increased risk of HPAI introduction into dairies through wild bird exposure.'
Today we have a preprint (albeit sporting an excellent pedigree, including Andrew Bowman & Richard Webby), which challenges the current hypothesis that bovine HPAI is being spread primarily by contaminated milking equipment.
While they confirmed that Bovine (B3.13) H5N1 efficiently infects the bovine mammary gland at very low infectious doses - and produces clinical disease and reduced milk production - they were unable to duplicate the spread of the virus via contaminated milking equipment under controlled experimental conditions.
The authors wrote:
While contaminated milking equipment is strongly hypothesized to be the primary route of exposure on-farm5,6, our experimental findings did not confirm this, falling short of an explanation for the apparently frequent on-farm transmission.
While small sample sizes in experimental settings may limit the ability to observe transmission, this also raises important questions about whether real-world farm conditions present higher risks than can be reproduced in high-containment facilities.
Other agent, host, and environmental cofactors that might contribute to transmission cannot be ruled out and must be explored as this study demonstrates critical gaps in our understanding of transmission.
While I've posted the abstract and a few excerpts, this is a fascinating report, and deserves to be read in its entirety. I'll have a postscript after the break.
Andrew Bowman1, Carolyn Lee2, Natalie Tarbuck1, Hannah Cochran1, Bryant Foreman1, Patricia Boley1, Saroj Khatiwada1, Alok Dhakai1, Khadijat Adefaye1, Jennifer chrock1, Mohammad Jawad Jahid1, Thamonpan Laocharoensuk1, Raksha Suresh1, Olaitan Shekoni1, Erika Stevens1, Sara Dolatyabi1, Christina Sanders1, Elizabeth Ohl1, Devra Huey1, Juliette Hanson1, Renukaradhya Gourapura1, Richard Webby3, Cody Warren4, Scott Kenney1
This is a preprint; it has not been peer reviewed by a journal. https://doi.org/10.21203/rs.3.rs-6900680/v1
This work is licensed under a CC BY 4.0 License
Abstract
The discovery that highly pathogenic avian influenza A(H5N1) virus exhibits a strong tropism for the bovine mammary gland1–4 represents a major shift in our understanding of influenza A virus host range and tissue specificity.
We conducted a comprehensive series of experimental studies with influenza A(H5N1) B3.13 genotype in lactating dairy cattle to address several key questions related to the viral dose required to establish infection, routes of exposure that lead to transmission, and factors contributing to the morbidity and mortality observed on farms. We demonstrate that intramammary exposure to as few as 10 TCID50 is sufficient to establish robust infection, shedding of high viral titers in milk, and clinical mastitis.
Despite evidence of such a low infectious dose, we were unable to recapitulate transmission to sentinel cows via contaminated milking equipment and close contact with infected animals under experimental conditions. High-dose intramammary exposure to influenza A(H5N1) drives severe clinical outcomes and mortality observed in dairy cows on-farm, while respiratory and oral exposure are less likely to establish productive infection and associated morbidity.
This study challenges current hypotheses of influenza A(H5N1) transmission on dairy farms5,6, raising important questions about potential agent, host, or environmental cofactors that contribute to the spread of the virus.
(SNIP)
DISCUSSION
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.
(SNIP)
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 adaptation, 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 deaths31–33—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.
The fact that we are now 15 months into this crisis and still don't have a solid understanding of how the HPAI virus is transmitting among dairy cattle should give all of us pause.
Testing of cattle remains limited, and is often at the discretion of the farm owner, many of whom are reluctant to cooperate over fears of economic losses, and the stigma of quarantine.
We've also seen farm workers reluctant to report illnesses, or refuse to be tested, over fears of losing their jobs (see EID Journal: Avian Influenza A(H5N1) Virus among Dairy Cattle, Texas, USA) or of an encounter with immigration officials.
Reporting has slowed to a glacial pace, making it very hard to know exactly where the risks from H5N1 currently stand.
While we've been lucky so far - and bovine H5N1 hasn't sparked a large-scale human outbreak - these viruses continue to evolve along numerous pathways, and what emerges tomorrow, or next year, may not be so constrained.
Should that day ever come, we'll rue all of the days we squandered while we optimistically waited for the virus to `burn itself out'.
