2025 is Here - Will it Bring a Pandemic?
For perspective, who had H5N1 in DAIRY CATTLE on their radar January 1st, 2024?
One year ago, I wasn’t composing blogs; however, my number one animal health concern was the inevitability of African Swine Fever entering the continental North American swine population. It is dangerous for anyone to confidently put timelines on pestilence and even more foolhardy to put it in print! So read my scenarios later in this post with appropriate skepticism!
Regardless, I’ve chosen 3 end-of year links to highlight in this column for your review. The first is a column from my long-time blogging mentor Michael Coston, who looks back at the COVID19 pandemic origins for insights into how it was (mis)handled for insights into today’s situation. it’s not a pretty picture:
Avian Flu Diary: The Wrong Pandemic Lessons Learned
Many of us hoped that after the COVID debacle of early 2020, we'd come out of the pandemic both wiser and better equipped to deal with the next global health crisis.
Instead, we seem to be less well prepared today than we were a decade ago.
While we may get lucky, and skate through 2025 - or beyond - without seeing another pandemic, at some point our luck will run out (see BMJ Global: Historical Trends Demonstrate a Pattern of Increasingly Frequent & Severe Zoonotic Spillover Events).
And when that happens, we'll truly wish we had the time back we are squandering now, pretending the next pandemic won't happen on our watch.
I’ll never forget reading his blogs back in early 2020 with disbelief, as reports of China shutting down travel to and from Wuhan failed to arouse significant U.S. or world response. It was obvious to many of us reading of these events that this was an air-borne highly contagious coronavirus that would inevitably spread world-wide. It became clearer to me that our modern political systems are unable to deal with excessively dire news. (An interesting counterpoint to this can be derived from the current Netflix series on Winston Churchill, a man who spared his people no bad news related to the horrors they faced in 1939. It is a nuanced story of a flawed man who used honesty, grit, and stubborn courage to will his nation to victory against great odds.)
I’m including a second link mainly because it provides more insight into the USDA’s ongoing approach to H5N1b2.3.4.4 B3.13 in dairy cattle, in the face of continuing doubt harbored by others in the scientific community:
Experts Lament 'Anemic' Response to H5N1, Worried About What 2025 Will Bring
…Adalja thinks it's likely that the B3.13 genotype of H5N1 will become endemic in dairy cattle, but federal officials have said that's not the case just yet.
"We know we can effectively eliminate the disease from herds even in the absence of a vaccine," Eric Deeble, deputy under secretary for marketing and regulatory programs at the USDA, said during a press briefing on December 18. "We are quite confident we can continue those efforts to eliminate the virus from the national herd."
He added that a bovine H5N1 vaccine program is under investigation, with seven vaccine field safety trials approved by the agency. It's not possible to predict how long development of a bovine vaccine will take, he noted.
"A vaccine would be helpful [in eliminating the virus from the herd], and it's part of the reason we're pursuing it with a great deal of vigor," Deeble said. "But no, I don't think we're considering B3.13 to be endemic in the herd, and I think we can eliminate it."
Adalja cautioned that if the virus becomes endemic in the herd, that creates "a new occupational risk for dairy cattle workers, decreased milk production for dairy cows, and eventually you'll have people shunning U.S. dairy products."
"I think people only think about the short run and that's what's happening with the shortsighted policies from the agricultural sector and the farmers themselves," Adalja said. "I don't expect that thinking will get better."
"It's been a flawed response from the very beginning," he added. "It would be good if the Trump administration took this threat seriously and made an Operation Warp Speed type of project to develop better countermeasures, better vaccines, better diagnostic tests for this."
"Maybe people were lulled into complacency by the fact that we had not seen severe infections in humans before, but we've now had a few people who've ended up in a hospital with this infection," Lawler said. "It just reminds us that this is a dangerous virus."
Regarding the USDA position, I’d like to see clear evidence that H5N1 has been reliably eliminated from multiple dairy herds. I know Colorado, for instance, currently has 64 herds with “negative” bulk tank tests, meaning CT values >35. However, one herd recently briefly returned to positive status before apparently dropping back above a CT>35. Are all recovering herds consistently showing 0 (>40) CT values? What about herds in Texas, Michigan, and Idaho? National bulk tank testing may eventually provide more clarity regarding this issue of low levels of infection versus 0 infection. However, in talking with a few people in contact with field veterinarians, it seems that intermittent recurring bulk tank positive CT values indicate that the virus remains active in some “recovered” herds. Time will tell whether residual virus lead to new clinical infections and/or mutated strains, or whether the virus does eventually completely die out.
Finally, 2 NIH officials wrote an editorial in the New England Journal of Medicine assessing the threat of H5N1 based on the most current information, which included 2 separate studies released in the same journal issue. Here is the commentary:
The Emerging Threat of H5N1 to Human Health | New England Journal of Medicine
Here are the 2 studies released in the same NEJM issue; one relates to the adolescent girl in British Columbia severely ill with anH5N1 infection; the other is a summary of epidemiological findings from multiple human H5 cases in California:
NIH separately wrote a summary of the officials’ full commentary (linked above) as a press release from their offices; I posted a section for further comments:
NIH officials assess threat of H5N1 | National Institutes of Health (NIH)
…Against this backdrop, Drs. Marrazzo and Ison say there are four keys to controlling the current outbreak. The first imperative is timely, effective collaborations among investigators in human and veterinary medicine, public health, health care, and occupational workers, such as dairy and poultry workers….
Their second key is a focus on the Canadian HPAI H5N1 patient, who developed respiratory failure and required life-saving medical intervention and treatment before recovering. The authors write that mutations found in the virus in this patient highlight an urgent need for vigilant disease surveillance to identify and assess viral changes to evaluate the risk for person-to-person transmission. Effective surveillance, they say, requires that complete genomic sequencing data from animals and people are made rapidly and readily available.
Without information pertaining to where and when isolates were collected, the data cannot be linked phylogenetically to other reported sequences, limiting insight into how the virus is spreading, they write. These data would also provide opportunity for early detection of mutations that might portend avidity for human respiratory epithelium, which may require as little as one mutation in the virus.
Third, researchers must continue to develop and test medical countermeasures—such as vaccines and therapies that eliminate or alleviate disease—against H5N1 and other influenza viruses. Fortunately, current vaccine candidates neutralize the circulating strains, which so far are susceptible to antivirals that could mitigate transmission and severity of illness, they write.
Lastly, Drs. Marrazzo and Ison encourage people to take precautions to prevent exposure to the virus and minimize the risk of infection. For example, people who work with poultry and cows should use personal protective equipment and educate themselves about occupational risks when working with birds and mammals, as CDC and USDA have repeatedly recommended…
As I’ve highlighted above, a core deficiency continues in timely analysis of complete genomic sequencing data (and associated metadata) from animals and people. This is not a new concern, and frankly, I don’t expect changed policies or performance from the NVSL-NAHLN system on the animal side to improve the situation. We operate both by law and tradition under a well-entrenched national reportable animal disease system with long-standing outbreak investigation and confidentiality policies recognized by federal, state and industry partners. USDA will likely continue to handle H5N1, a dynamic changing multi-species zoonotic virus requiring maximum transparency for effective One Health readiness, as a HPAI delayed “confidential” reporting process designed to minimize industry trade disruptions. Even with mandatory bulk tank testing, it will be interesting to see to what degree positive (and negative) results are released, the degree of temporal and geographical specificity, and the timeliness of sequence sharing. Past performance would indicate slow progress on all these metrics.
I can foresee three situations that might improve animal surveillance metrics in 2025:
voluntary industry surveillance and sequencing programs to provide transparency and protect workers and product reputation
state-level voluntary reporting of sequences and metadata
federal designation of H5N1 as a disease of public health concern with required surveillance and testing of susceptible animals
Personally, I don’t see any of these on the near-term horizon at the current threat level, given the incoming administration’s likely negative approach towards federalized public health pandemic preparedness actions. I think we are inevitably deigned to be reactors and not pre-outbreak intervenors to an onward transmitting zoonotic event in 2025.
Now for the speculative part my Initial New Year 2025 column-what could unfold this year specifically with H5N1 or with zoonotic threats in general? Your insights are as clear as mine, but here are 4 somewhat random plausible scenarios to consider:
H5N1 B3.13 mutates at the cattle-human interface to gain onward human to human spread; the disease remains mild in general, however infants, the elderly and immunocompromised are susceptible to severe illness and death from HTH spread.
H5N1 D1.1 spreads from infected poultry to other farm livestock, e.g. lactating dairy cattle and swine. It becomes H5N1 2.0 in lactating dairy and/or reassorted H5N1 in swine, with either/both species shedding virus of greater pathogenicity to human contacts.
H5N1 B3.13 mutates in cattle towards greater respiratory and neurological affinity, leading to wider clinical disease in non-lactating cattle, including beef, as well as greater potential pathogenicity in human spillover infections.
A delta-coronavirus mutation in China (or Haiti, or the U.S.) infects both humans and pigs, with a highly infectious human version circling the world (“COVID25”).
None of these scenarios are a lock, but neither are they beyond the realm of possibility. Regardless, it’s unlikely that any of these scenarios will play out exactly as imagined. B3.13 may “peter out” as the USDA and dairy industry are counting on, and the current D1.X genotype may be H5N1’s final mammalian adaptation nightmare. However, current trends do not point in those directions, and we need to plan for major zoonotic H5N1-related scenarios in the coming year.
In my view our technological advances for countermeasures are more hopeful. Diagnostics, treatment, and vaccine technologies are moving forward faster than we can approve and incorporate their adaptation. If the worst happens with H5N1, I hope and pray that reactive politics and false budget concerns will not prevent rapid deployment of lifesaving mRNA vaccine technologies, for example, such as occurred with COVID19.
As 2025 dawns, we have the knowledge and laboratory infrastructure in place, but not fully funded and mandated for decisive action. Hopefully we’ll find our “Churchills” in the current trust and courage crisis to meet the challenges we are almost certain to soon face.
John