One Year Later-"It Has Been Determined" that Retrospective Infected Dairy Herd Serology can be Disclosed

As widely suspected, H5N1 infection in dairy herds spreads widely in both lactating and non-lactating animals, most likely by classical influenza oronasal routes

Opaqueness in decision-making was an eye-opener for me 22 years ago when I moved to federal service from the private sector. Controversial or unpopular decisions came down from above with no fingerprints, just a third-party attribution, e.g. “it has been determined…” I came to quickly realize that not personally owning a tough to-defend decision is a form of professional survival in the chain of command of the regulatory environment.

Looking back one year ago, USDA and the dairy and cattle industries were firmly in damage control related to H5N1 2.3.4.4b B3.13. Positive PCR results were limited to lactating dairy cattle herds; looking for additional positive herds by ELISA or HI serological sampling was only looking for more trouble! The practical result in the regulatory field was that PCR sampling was strongly encouraged for milk samples and tolerated for nasal swabs in lactating dairy cattle and other species. Serological sampling was downplayed as not validated for cattle.

Early outbreaks with dramatic clinical signs of mastitis with huge viral loads in affected quarters in up to 20% of lactating cattle misled investigators into postulating an exclusive udder-based milk-based type of disease transfer as the primary mode of infection for H5N1 in lactating dairy cattle. The USDA-dairy industry establishment quickly latched onto this as the consensus theory for an exclusive H5N1 2.3.4.4b B3.13 spillover into dairy cattle, which could be controlled with affected lactating cow movement controls and increased biosecurity practices, leading to eventual exhaustion and elimination of the infection. This disease transmission theory conveniently avoided involvement of other classes of cattle in the outbreak, simplifying disease containment challenges from a regulatory and management standpoint. As a result, federal-state-industry collaborators rapidly developed an animal movement and voluntary clinical illness surveillance program based on this flawed milk-udder transmission-based influenza virus spread model in dairy cattle.

Since the beginning of the H5N1 dairy outbreak, many of us called for systematic serological surveys in infected, recovering, and neighboring dairy and beef herds to better understand the epidemiology within and between infected and susceptible herds. While research-focused serological assay work has been done outside of NAHLN-NVSL official testing under the Federal Order, research testing results can only be reported with the approval of the appropriate state animal health official(s) where work is originated. The practical effect is that USDA-APHIS has expected that serological testing will not be reported in non-lactating dairy cattle for any purpose other than case diagnostics, under the review of NVSL without prior approval, and state animal health officials have concurred with that expectation.

Serological testing has sensitivity and specificity limitations at the individual animal level; those limitations can provide enough uncertainty to require validation studies for use. However, multiple influenza ELISA tests have now met validation requirements for use in cattle, which are not a requirement for test utilization for research purposes in any event. The regulatory risk has always been that widespread serological sampling would blow a hole in the exclusive lactating cow theory of H5N1 infections. Those findings in turn would bring many of the existing H5N1 dairy herd management and movement assumptions and strategies into question.

Somehow, we’ve managed to let 12 months pass without allowing any reporting of retrospective serological results in affected dairy cattle herds. However, recently “it was determined” that these results could be released, with the following study finally reaching pre-print status:

The impact of influenza A H5N1 virus infection in dairy cows

Please read the study in detail for a lot of great work regarding the costs of this disease on individual animals and on this specific Ohio dairy farm. Dr. Kay Russo wrote an excellent column on LinkedIn regarding its findings:

Kay Russo-RSM Consulting-LinkedIn Post

For the purposes of this column, I’d like to concentrate on a couple of paragraphs in the research paper’s discussion related to the serological findings, which were finally approved for release. Remember that these samples were drawn on June 20th, 2024, nearly 9 months ago:

The seroprevalence in the target study was estimated to be 89.4% (570/637) in animals that were on the farm during the clinical phase of the outbreak (March 19 to April 11, 2024) suggesting a high transmission efficiency of the virus among cows. Importantly, of the 570 seropositive animals 463 (83.7%) were not clinically affected by influenza A H5N1, indicating a large proportion of subclinical infections. Although the precise mechanism of transmission of HPAI H5N1 virus in dairy cattle remains unknown, this is consistent with infections with other influenza A viruses which can quickly spread through susceptible mammalian populations including in humans, dogs and swine 18,19. Another important observation from our serological study is the detection of antibodies in 17/42 (40.5%) of the cows that were in the dry period during the clinical outbreak in the farm. These findings suggest that non-lactating animals are also susceptible to H5N1 virus infection and as such should be considered as potential source of the virus. This is especially important when animals in the dry period are introduced into farms as replacement cows. Notably, when we assessed milk production in seropositive subclinical animals, we did not observe a decrease in milk production in these cows, indicating that clinically affected animals are the main group of animals contributing to decreased milk yields due to HPAI H5N1 virus infection

H5N1 2.3.4.4b B3.13 transmitted widely throughout this herd to both lactating and nonlactating cows on the property (see diagram of barn lay-out above - note hospital pen within dry cow barn), with a subset of the lactating cows becoming clinically ill with mastitis. The source of the virus was pre-clinically infected lactating cows imported from a pre-clinically infected Texas herd.

I actually wrote about this herd last July; it was one of several herds summarized in a research paper released at that time:

Let's Tackle the Nature H5N1 in Dairy Paper (Dimitrov-Diehl) in More Detail...

Received: 22 May 2024 Accepted: 18 July 2024 Published online: 25 July 2024

Here was some narrative from that paper I reported related to Herd #3-the Ohio herd, which I highlighted at the time:

Clinical animals shed virus at a lower frequency in nasal swabs (6/25) and urine (2/15), and no viral RNA was detected in feces. In non-clinical animals, viral RNA was detected in 6/19 nasal swabs and 4/8 urine samples, indicating subclinical infection.

…Although the tissue sample size included in our study was small, isolation of the virus in lung and supra-mammary lymph nodes (which were also positive for viral RNA and antigen) suggests that other organs may also play a role in the virus infection dynamics and pathogenesis in dairy cattle. The initial site of virus replication remains unknown; however, it is possible that the virus infects through respiratory and/or oral routes replicating at low levels in the upper respiratory tract (e.g. nasal turbinate, trachea, and/or pharynx), from where it could disseminate to other organs via a short and low-level viremia.

The blood samples from this herd were drawn on June 20th, about a month after the paper was submitted, indicating that the Ohio State-Cornell researchers were prudently following up on the subclinical illness issue suggested by the reported PCR findings. That subset of researchers likely had preliminary serology results and strongly suspected classical oronasal viral infection in the Ohio herd by the date of the paper’s release, as they implied in their summary language.

Reported confirmation of those serological findings last summer would have been paradigm shifting at a very critical time in the H5N1 dairy outbreak. Instead, we muddled through the fair season, World Dairy Expo, and the Colorado/California dairy/poultry outbreaks with continued USDA insistence that non-lactating dairy animal movement was safe, and that outbreaks were exclusively due to biosecurity deficiencies and clinically infected lactating cow movements. No U.S.-based dairy cattle, beef or swine H5N1 serosurvey results from researchers were published to my knowledge until the ARS-infected colostrum calf study. One “errantly” reported interim lowly positive feral swine serology survey result was withdrawn, and no further results from the Wildlife Services feral swine serosurvey have been reported since. NVSL remains officially in charge of official approvals for serological test reporting, and that process has been repeatedly employed to manage release of results, especially for officially notifiable diseases.

That brings me back to my title - apparently “It Has Been Determined” that the serological results from the Ohio herd can now be published nearly 9 months after their collection…I won’t speculate what precipitated the change: 1) D1.1 as a new genotype shown to be of respiratory origin; 2) published ARS work demonstrating oral transmission of virus to calves; 3) a change in USDA leadership; or 4) all of the above combined.

Regardless, the old talking points on H5N1 2.3.4.4b B3.13 transmission have become so untenable that moving the dialogue forward to better deal with new mixed B3.13 and D1.1 challenges in livestock is the more critical challenge. Serology will become more challenging with multiple strains, including questions of cross-protection and strain specificity in serological results. Those questions can be teased out if results are published and critiqued across multiple research institutions.

Updated understandings regarding subclinical and respiratory H5N1 infections will greatly complicate safe animal movements and food safety questions for the dairy and beef industries. The entire USDA H5N1 “story” for a year was written to minimize movement disruptions, exports, and food safety concerns for dairy cattle and the beef industry. The virus needed to remain “in the udder” to minimize disruptions. It turns out that influenza in any species has never been that cooperative and exclusive…

Now we need to utilize serology as one tool of many to survey just how widespread the risk may be across our livestock sectors, then use PCR and other molecular technologies to home in on the riskiest areas. If we get too cavalier in ignoring them, we can likely count on bulk tank results, dead cats, poultry outbreaks, or human cases to rudely remind us that we’re not looking hard enough.

We love to blame all our H5N1 miseries on wild birds, but as Dr. Kay Russo so aptly stated in comments following her LinkedIn post commentary regarding this research:

28 million layers were lost to spillover from cattle last year, compared to 14 million from migratory waterfowl point source introductions. So 2/3 of the layer cases were due to cows last year.

In a Breitbart article, USDA Secretary Brooke Rollins blithely assures us that increased biosecurity supported by the Trump Administration will negate the need for vaccines (Exclusive — USDA Secretary Brooke Rollins: Vaccines ‘off the Table’ in Fight for Lower Egg Prices). I have to wonder how that’s going to work out for poultry flocks next to dairy (or feedlot) H5N1 B3.13 or D1.1 outbreaks, especially when she is also taking cattle vaccines off the table in the same conversation? I’ll give Secretary Rollins credit for one thing - she definitely does not hide her intentions in 3rd person language anonymity! She will own these comments!

Finally, the Bloomberg School of Public Health yesterday released a new piece advocating more action regarding H5N1 across the One Health spectrum:

New Bird Flu Spillovers Threaten U.S. Milk and Eggs | Think Global Health

I think this graph nicely illustrates the complexity of the issues we face, although it likely oversimplifies the dynamics of the production agriculture influenza ecosystem between farms, species, transportation networks, and multiple farm workers and contractors:

I frankly don’t hold out much hope for proactive creative responses to these challenges in the short term; we are likely doomed to “too little-too late” half-hearted responses with continued hope for the best current approaches. We have unparalleled cutting-edge surveillance, analytical, and vaccinology tools at our disposal. Unfortunately, “it has been determined” by today’s leaders that we are powerless right now to employ them due to…what???

Tomorrow’s leaders will overcome those excuses.

John