ARS Demonstrates H5N1 2.3.4.4b B3.13 Oral Transmission via Infected Colostrum to 2-Month-Old Calves
Demonstrated oral transmission plus widespread D1.1 adds urgency for H5N1 for the entire livestock and poultry industry
Earlier this week USDA-ARS National Animal Disease Center (NADC) researchers released a research preprint via the CABI Digital Library:
I had made reference to the highlights of these findings in an earlier column which one of the researchers, Dr. Bailey Arruda, had graciously shared with the audience at the 2024 Leman Swine Conference (A Week of Papers Published and California H5 Dialogue Amidst More Infected Herds). Now we have the entire paper in preprint to review; here is the Abstract in full:
Abstract
Highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b genotype B3.13 was confirmed in a dairy cow in Texas on March 25, 2024, by the US Department of Agriculture (USDA) National Veterinary Services Laboratories (NVSL) in response to a multi-state investigation into milk production losses. The amount and duration of virus shed in milk from the inoculated mammary quarters point to milk as a primary source of virus spread within and between dairy herds. Pasteurization has been shown to inactive the virus in milk, however, domestic cats consuming raw milk from affected cows developed fatal systemic influenza infection. Investigations on affected dairy herds demonstrated the presence of viral RNA in milk samples for up to 2 weeks before the appearance of clinical signs and diagnostic confirmation of infection. During this lag, unpasteurized milk may pose a risk to calves. Here, we sought to determine if H5N1 genotype B3.13 strain could be transmitted to calves fed unpasteurized milk from virus positive lactating cows. Five Holstein calves of approximately 7 to 11 weeks old were fed 0.95 L of unpasteurized milk twice a day via bucket. Milk was collected from two lactating Holstein cows inoculated by an intramammary route and fed to four calves for four days. Milk from two non-inoculated cows was fed to one negative control calf for four days. After four days all five calves were fed milk from non-inoculated cows. Calves fed infected milk showed clinical signs including nasal discharge, mild fever, mild lethargy, loose stool and slightly increased respiratory effort for 5-6 days. Signs of clinical disease were mild and may not be recognized under field conditions with other environmental or health stressors. Viral RNA was consistently detected in nasal swabs from all four calves from 2 to 4 DPI, with consistent detection persisting after calves were transitioned to being fed milk from non-inoculated cows. Infection was confirmed by viral RNA detected in nasal swabs, antigen and viral RNA detection in lung lesions, lymph nodes and pharyngeal tonsil, and seroconversion. Ct values of the nasal swabs were significantly correlated (-0.55) with lethargy in the calves. As Ct values dropped, and viral load increased, calves became more lethargic. Milk diverted from the human food supply in H5N1 positive dairy herds or from suspect cows should not be fed to calves without pasteurization. The determination of routes of transmission like the study described here is an essential first step to inform subsequent research on intervention and vaccination strategies
I want to emphasize several points that resonated with me from this work as I apply it to the entire evolving H5N1 dairy and farm livestock situation:
This is a true infection, not a “contaminant” from the oral ingestion of the colostrum, with virus shown in nasal swabs after withdrawal of the infected milk.
These calves are at least theoretically capable of onward transmission of infection to other animals, depending on shedding levels, route of transmission, and infectious dose for the receiving species.
While not directly studied, evidence of virus in the lungs and lymph tissue would suggest at least a transient systemic infection; further studies are warranted to explore tissue distribution over the course of infection.
Oral inoculation studies need to be extended to other age groups. These were not neonates; they likely have active rumens at 2 months. Does oral transmissibility extend to adult cattle? Does it extend to non-dairy breeds?
With mild symptoms we are likely missing infections in non-lactating cattle, especially with the B3.13 genotype. (We really have no data yet on symptoms in cattle with the D1.1 genotype- pleased weigh in, Nevada and USDA!) The researchers carefully state that clinical signs were subtle, implying that clinical illness may easily be overlooked in non-lactating animals, or even lactating animals that fail to show mastitis-compatible symptoms. This study adds evidence to calls for more careful whole herd examinations of entire dairy herds incubating H5N1 infections, beyond examination of just symptomatic lactating cows. Furthermore, this examination needs to occur much earlier than when clinical signs appear in lactating cows, because these mild transient respiratory symptoms likely occur just prior to or concurrently with bulk tank CT values going positive in incubating herds.
Is the oral route a common method for within herd or even between herd spread? Cows love to lick!
Whether it is other cows’ noses, udders, a worker’s face, dust, ‘snot”, etc., it’s not hard to imagine ingestion of some level of virus through the mouth. What is the “oral” infectious dose? Once we allow that the mouth-nose could be the entry point for infection, all sorts of possibilities open up as fomites or active sources of infection.
Unfortunately, oral infection also really opens up non-lactating dairy cattle as additional viral targets, i.e. other classes of dairy, as well as all classes of beef. Neither the regulatory nor ag commodity groups want to go there with H5N1 surveillance and zoonotic awareness, but that is where we are at.
Additionally, the arrival of D1.1 has further opened the floodgates of livestock vulnerability. What we now “know” about B3.13 we need to relearn regarding D1.1 (or the next genotype iteration). We add pigs to the mix because we already know that closely related D1.2 has been found in pigs. Worse, D1.1 seems to be endemic in wild birds in nearly every state and is epizootic in poultry in multiple geographical areas with concurrent high concentrations of dairy, beef, and swine.
Western Ohio and Eastern Indiana
As of February 11th, we had over 60 confirmed infected poultry premises on the Ohio-Indiana border in the following counties:
These counties are also home to large dairy, beef and swine populations, as can be visualized with this tool from the Ohio State University: Spatial Agrometrics Tool for Livestock Estimation (utilizing 2017 NASS county level data).
Despite our collective qualms regarding cattle and swine H5N1 surveillance, how can we repopulate million head-plus layer operations without knowing for sure that commercial livestock operations within surveillance zones are negative for H5N1 2.3.4.4b B3.13 and D1.1? USDA is proposing to require increased biosecurity assurances from the poultry industry. In return state and federal authorities must assure the poultry industry that H5N1 is not sitting in livestock herds within their areas of risk.
State “silo testing” for the dairy industry is an admirable half step but is too intermittent and non-targeted to assure negative status for dairy herd premises level assurances. Individual dairy herds in poultry surveillance zones should be evaluated and bulk tank tested. Swine and beef feedlots should also be evaluated and tested by PCR as appropriate to assure that H5N1 is not sitting there sub-clinically as a risk for reinfection to poultry flocks.
This will not be politically appealing or perhaps even possible. H5N1 has put us in an almost impossible situation. We need vaccines as soon as possible to relieve pressure on the poultry industry. My biggest fear is that we will have another severe human H5N1 case(s) and/or a human chain infection as this virus keeps probing.
I wish it was different, but that is the way I see it today…
John