Credit USDA
#18,183
Almost from the beginning of the outbreak of HPAI H5N1 in cattle, the focus has been on lactating cows (see USDA Statement On Mandatory Testing For Interstate Movement Of Cattle). They show the most obvious clinical signs of infection (including thickened, yellowed, and reduced milk production), are more easily monitored, and could plausibly be infected by contaminated milking machines.
Testing of non-lactating cattle has been extremely limited, and is only recommended if there are clear clinical signs of infection.
While the respiratory spread of H5N1 among cattle has not been ruled out, the focus has been more on other factors.
In the APHIS/USDA epidemiological investigation into the spread of H5N1 in Michigan, they cited the movement of livestock, farm equipment (including trucks), and personnel as contributing to the spread of the virus.
Questions remain, however, over how the virus has managed to spread so quickly across the nation.
Today we've a preprint from government researchers at the National Animal Disease Center in Ames, Iowa, which finds there may be other plausible routes of transmission worth investigating, including via the respiratory route.
Tests were conducted on both heifers (young female cows that have not given birth) and lactating cows, and while heifers exposed via the respiratory route showed mild or sub-clinical symptoms, their infections were confirmed by RT-qPCR, lesions, and serology.
Whether, or how much, non-lactating cows are involved in the spread of HPAI is unknown. But this study demonstrates it is possible to infect heifers via the respiratory route, and that once infected, they may not show overt signs of illness.
I've only reproduced the Abstract and an excerpt from the discussion, so follow the link to read the full report.
Experimental reproduction of viral replication and disease in dairy calves and lactating cows inoculated with highly pathogenic avian influenza H5N1 clade 2.3.4.4b
Amy L. Baker, Bailey Arruda, Mitchell V. Palmer, Paola Boggiatto, Kaitlyn Sarlo Davila, Alexandra Buckley, Giovana Ciacci Zanella, Celeste A. Snyder, Tavis K. Anderson, Carl Hutter, Thao-Quyen Nguyen, Alexey Markin, Kristina Lantz, Erin A. Posey, Mia Kim Torchetti, Suelee Robbe-Austerman, Drew R. Magstadt, Patrick J. Gorden
doi: https://doi.org/10.1101/2024.07.12.603337
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Abstract
Highly pathogenic avian influenza (HPAI) H5N1 of the hemagglutinin clade 2.3.4.4b was detected in the United States in late 2021 and continues to circulate in all four North American flyways to date. In addition to impacting poultry, these HPAI viruses caused mortality events in wild bird species and wild mammals. Transmission in multiple host species raises the concern for mammalian adaptation. On March 25, 2024, HPAI H5N1 clade 2.3.4.4b was confirmed in a dairy cow in Texas in response to a multi-state investigation into milk production losses.Over one hundred positive herds were rapidly identified in Texas and eleven other U.S. states. The case description included reduced feed intake and rumen motility in lactating cows, decreased milk production, and thick yellow milk. The diagnostic investigation revealed detections of viral RNA in milk and mammary tissue with alveolar epithelial degeneration and necrosis, and positive immunoreactivity of glandular epithelium by immunohistochemistry. A single transmission event, likely from avian species to dairy cattle, followed by limited local transmission preceded the onward lateral transmission of H5N1 clade 2.3.4.4b genotype B3.13.We sought to experimentally reproduce infection with genotype B3.13 in Holstein yearling heifers and lactating cows. The heifers were inoculated by an aerosol respiratory route and the cows by an intramammary route.
Clinical disease was mild in the heifers, but infection was confirmed by virus detection, lesions, and seroconversion. Clinical disease in lactating cows included decreased rumen motility, changes to milk appearance, and production losses consistent with field reports of viral mastitis. Infection was confirmed by high levels of viral RNA detected in milk, virus isolation, lesions in mammary tissue, and seroconversion.This study provides the foundation to investigate additional routes of infection, transmission, and intervention strategies.
(SNIP)
The interspecies transmission of H5N1 clade 2.3.4.4b to many mammal species, now including cattle with genotype B3.13, is unprecedented in our understanding of avian-adapted IAV 32,33.
This raises concern for other mammalian hosts, including pigs and other domestic livestock and pets, and particularly for humans. The human cases in the United States have been clinically mild and limited in number 4,5 , but concern remains as the H5N1 continues to expand into new hosts, spread geographically, and reassorts with other avian or mammalian subtypes.
The possibility of H5N1 becoming endemic in cattle increases as the number of infected herds continues to rise 1 . Pasteurization was shown to inactivate virus and retail milk remains negative for infectious virus, thus not a risk for human consumption when processed according to Food and Drug Administration standards 34. Unpasteurized milk and dairy products are a risk to humans and other animals. Milk diverted from the human food supply in H5N1 positive dairy herds or from suspect cows should not be fed to other farm or peridomestic animals.
The sustained transmission among dairy cattle is an animal health crisis due to production and economic losses and is a public health challenge due to occupational exposure on dairy farms.
The development of reproducible experimental challenge models like the ones described here is the essential first step to inform subsequent research on intervention and vaccination strategies. Although limited in the number of animals due to their size and high containment space requirements, we reproduced the clinical observations from the field of viral mastitis due to HPAI H5N1 infection alone and confirmed respiratory involvement.
Further studies to understand transmission, refine the pathogenesis model, and define the kinetics of protective immunity in cattle infected with HPAI are urgently needed.
It seemed perfectly obvious 3 months ago that we should be casting a wide net when testing for HPAI in livestock, but the prevailing attitude has been `don't rock the boat.' Testing remains largely voluntary, and there are more incentives for farmers to hide an outbreak than report one.
As a result, we are now 4 months into this crisis, and basic questions - like how the virus is spreading in cattle - remain only partially answered.
Of course, by the time we know those answers, the virus may have acquired a new set of skills.
Stay tuned.
