Swine Influenza - More Complicated Than We Ever Imagined
The collaborative USDA-University-Industry Swine Influenza A Virus Surveillance Program, initiated prior to the 2009 Pandemic, built a powerful research network with impressive findings
Today I want to share a small subset of research papers I’ve found informative in an evolving, but still incomplete understanding of Influenza A ecology in commercial swine herds. As a farm kid in the 1960’s we experienced H1N1 as seasonal acute viral infection. We really didn’t understand (or care) where it resided in the “off season”- it probably cycled asymptomatically in sow herds - who knows and no one really cared! However, in the fall with weather stress, many producers got “barking pigs” or acute influenza in the summer pig crop of finishing pigs. Veterinarians put them on expectorants and sulfa in the water; they improved in about 3-5 days, as they likely would have with no treatment. It might happen again in spring with the winter pig crop - the common factor was that it usually developed in young (naive) groups of finishing pigs, not so much in the breeding herd.
This pattern evolved as pig production went from 2 butcher hog crops per year to multiple groups and eventually to weekly farrowing. Farms now had weekly groups of naive pigs for infection from periodically shedding sow herds. Additionally, H3N2 influenza showed up in people and was soon passed on to pigs as a second strain of concern. Additional strains of H1N1 (and soon reassorted H1N2) began to mutate in pigs (and people).
Frankly, the veterinary community was pretty ignorant regarding the zoonotic issues with swine influenza in either direction in the 70’s-90’s. It became apparent as science advanced that “swine flu” occasionally showed up in people - in fact a whole “swine flu” emergency vaccine program was developed by CDC in 1976 after a small outbreak with one death was diagnosed in soldiers at Fort Dix NJ. The infection never took off as a full outbreak, and concerns over Guillain-Barre side effects from the emergency vaccine aborted its use, leading to charges of over-response to a public health non-emergency. The whole episode became somewhat of a public health embarrassment.
Conversely, I don’t recall it being on this young veterinarian’s radar that human influenza could be passed to pigs as being a big issue of concern for swine population veterinary medicine. We knew that H3N2 had somehow “appeared” in pigs, likely as a “one off” from a human spillover, but we really weren’t investigating much beyond hemagglutination inhibition (HI) serotyping in attempting to differentiate subtypes within H1N1 and H3N2 strains. Sanger molecular sequencing did begin to appear about the time that I joined the federal service in 2003; however, it was far from a routine diagnostic process.
From the 80’s on the swine industry was moving rapidly to separate site production models with “naive” weaned pig populations and also rapidly losing control of swine influenza! We spent 20 years assuming that if we could just match the right “autogenous” vaccine strains with our farm isolates, infections could be controlled in nurseries and finishers. Results were variable and temporarily successful for the most part. It was extremely confusing to sort out all the theories on how to protect pigs as we identified an increasing array of “differing” influenza isolates each seeming to require new customized vaccine preparations for temporarily successful immunity. Autogenous vaccine companies had a field day preparing new bacterins for veterinarians and their clients in search of better influenza protection.
The industry has continued to struggle with developing effective protective immunity in weaned pigs. Sources of potential infection include: 1) viral shedding into weaned pigs from the sow herd, with breeding stock additions creating unstable resident influenza populations; 2) human virus shedding into both sow farms and nursery-finishers; and 3) occasional lateral “area spread” from neighboring farms. All are significant sources of risk, but it appears that a major key to control may lie in minimizing viral load and diversity of influenza virus in the sow herd via biosecurity, vaccination and replacement flow management.
Let’s pause at this point to review some pertinent research, before I cover some interesting presentations from the 2025 Leman Swine Conference in St. Paul in late September:
The first paper is an earlier collaborative effort led by Martha I. Nelson of the Fogarty International Center, National Institutes of Health, Bethesda, Maryland, with collaboration from an all-star international cast of influenza molecular researchers:
Through a large-scale sequencing effort, we identified a novel influenza virus of wholly human origin that has been circulating undetected in swine for at least 7 years. In addition, we demonstrate that human-to-swine transmission has occurred frequently (20 documented sequences) on a global scale over the past decades but that there is little persistence of human virus internal gene segments in swine.
The main finding from this older (2014) study was that “human to swine” zoonosis is much more common versus “swine to human” directionality in sequenced isolates, with the H and N human-derived segments showing more persistence in sequenced swine populations than the 6 human-donated internal gene segments. The swine-based 6 internal gene “TRIG cassette” seems really well adapted in swine and resistant to displacement by human influenza donor gene segments during reassortment. I personally found this paper to be an important affirmation to the swine industry that collaborative sequencing efforts cut “both ways”, i.e. while concerns with pig to human transmission led to CDC’s push for more swine sequencing work, in reality human to pig influenza transmission may be of larger concern to the swine industry in managing pig health. We need to be aware of human influenza H and N genes that are infiltrating our pig populations, with the implications that has for efforts to prevent zoonotic spread of influenza virus from people to pigs in swine barns.
A second significant study was published in 2020 in Transboundary and Emerging Diseases by Torremorell et al: Genetic variability of influenza A virus in pigs at weaning in Midwestern United States swine farms - PubMed. Unfortunately, this paper is behind a paywall, and I did not review it beyond the abstract; however, the work documented a lot of added complexity to the swine influenza ecological picture, particularly the relatively common finding of “mixed” genotypes of infections both in individual pigs and in groups of pigs at weaning! These are critical findings that I believe have been totally unappreciated in the past.
…The objective here was to evaluate the genetic diversity of IAV in pigs at weaning in farms located in the Midwestern USA. Nasal swabs (n = 9,090) collected from piglets in breed-to-wean farms (n = 52) over a six-month period across seasons were evaluated for the presence of IAV. Nasal swabs (n = 391) from 23 IAV-positive farms were whole-genome sequenced. Multiple lineages of HA (n = 7) and NA (n = 3) were identified in 96% (22/23) and 61% (237/391) of the investigated farms and individual piglets, respectively. Co-circulation of multiple types of functional HA and NA was identified in most (83%) farms. Whole IAV genomes were completed for 126 individual piglet samples and 25 distinct and 23 mixed genotypes were identified, highlighting significant genetic variability of IAV in piglets. Co-circulation of IAV in the farms and co-infection of individual piglets at weaning was observed at multiple time points over the investigation period and appears to be common in the investigated farms…Results reported here demonstrate previously unreported levels of molecular complexity and genetic variability among IAV at the farm and piglet levels at weaning. Movement of such piglets infected at weaning may result in emergence of new strains and maintenance of endemic IAV infection in the US swine herds.
This work has now been followed up with a 3rd recently published paper from collaborators at Minnesota and at St. Judes: Naturally occurring influenza reassortment in pigs facilitates the emergence of intrahost virus subpopulations with distinct genotypes and replicative fitness | mBio
…Here, 244 IAV plaques were isolated from 24 commercial pigs, resulting in 26 distinct genome segment constellations. About 33% (8/24) of pigs were infected with two or more different genotypes, with two pigs harboring two or more different subtypes. Our results indicate that few pigs in a population harbor significantly more genotypes than other pigs and generate most of the diversity, including the emergence of reassortants. However, detecting distinct genotypes during surveillance was dynamic, with most of the genotypes subsiding over time. All the IAV genotypes could replicate in various swine and human-sourced respiratory epithelial cells, and we observed that distinct reassortant genotypes recovered from a single pig could exhibit different growth abilities, especially in human cells. Overall, we demonstrated that multiple distinct IAV genotypes with distinct antigenic profiles and varying growth abilities on swine and human respiratory tracts can be shed simultaneously from a single pig, which contributes to the dynamic nature of IAV prevalence. The striking magnitude of IAV reassortment at the single pig level revealed in this study highlights the need to strengthen surveillance efforts and plans to eliminate IAV from swine farms because pigs have a high potential to produce diverse and potentially zoonotic influenza reassortant viruses.
The ecology of swine influenza evolution in large groups of weaned pigs is stunningly complex; in fact, it’s complex even at the individual pig level! We often speak of influenza “rolling the dice” for reassortment. It seems that the virus can roll the dice multiple times at the individual pig level over a long time period in subsets of pigs. I don’t know how to figure “odds” from this type of research; perhaps all we can say is that the work reinforces the zoonotic reassortment risk that exists, given all the variables present across each pig and the entire population.
On to the Conference Presentations
This brings us to work that was presented about a month ago at the Leman Conference in St. Paul MN, adding a bit more information to this complex picture. During an influenza breakout session University of Minnesota researchers updated us on some of the latest ongoing work related to understanding influenza diversity at the production flow and individual pig level. Here is slide from the presentation describing some of the earlier work in the ongoing studies:
This earlier work led to some questions now being addressed with current studies:
Here is a barn and pig flow diagram that illustrates how pigs were sampled in the current study. Note that pigs from 3 sow farms were commingled at weaning across 3 nursery flows (presumably to minimize age range in nursery groups), with periodic sampling conducted in the sow farms, twice in the nurseries, and once in the finishers as shown below:
Here is a slide showing positive samples with genotype results by stage of production:
The slides aren’t clear enough (nor is my memory); however, here are my take home points:
swine influenza in sow herds and nurseries is often a multi-strain challenge, even within individual pigs; this is much more immunologically challenging than the industry has traditionally attempted to address with traditional vaccines and diagnostics based on the single strain isolates from clinically ill swine.
both the breeding herd and weaners in the early nursery, which reflect pre-weaning sow exposure to influenza strains plus the occasional human zoonotic spillovers, have extremely diverse (and likely unstable) influenza genotype populations (large numbers of genotypes in both sample sets).
as time passes within closed groups (the later nursery groups and finishers), viral diversity resolves as less competitive strains die out with population isolation and building immunity. Most finisher sites go negative as immunity builds across multiple strains. Remaining positive sites have much less viral diversity (single genotype in 4 pigs).
As we think about endemic influenza management, whether in pigs or in dairy herds, these studies provide us some clues for success in beating back the virus, i.e isolation and biosecurity, perhaps paired with strategic strain-matched vaccination to enhance immunity.
The final presentation in the influenza session provided more insight along those lines. These principles have been used to decrease diversity and even eliminate influenza in sow barn populations with proper replacement flow and management, vaccination, and good human biosecurity (zoonotic spread prevention).
Negative Sow Herds-Elimination of Human Spillovers in Pig Populations
Dr. Emily McDowell of Pipestone Veterinary Services provided a very transparent discussion regarding that group’s successes and setbacks in producing influenza-free pigs in a talk entitled: Control and Elimination of Human Influenza Spillovers in Pigs. As a passionate One Health advocate, this presentation was worth the price for the entire conference to me! The lessons being learned here in the barns, supported by the labs are profound, worth more than 20 academic and esoteric “One Health Roundtables.”
Pipestone is a large integrated swine health, management, and production system company based out of Pipestone MN, with bold, progressive ideals in pork production. They own, manage and/or influence both seedstock multiplier and pig production units across multiple states. Disease elimination for animal welfare and production enhancement is one of their constant goals, whenever feasible. In an opening slide, Dr. McDowell listed their reasoning for eliminating swine influenza from their genetic multiplier and sow production units:
Dr. McDowell showed the Pipestone IAV cumulative incidence track record for the past 4 years:
For 2022-2024, the system was quite successful in keeping IAV out of 70% of the monitored sow units annually (30% became infected). They have suffered some setbacks in 2025.
Sow farms are taken to negative status through enhanced mass vaccination to boost general immunity, paired with a series of replacement in-movement restrictions. Once protocols indicate likely negative status, delayed introductions of influenza negative, vaccinated replacement gilts are resumed. The overriding concept is to “starve” the virus of new animals for infection before resuming vaccinated new animal additions. The swine industry has used this concept repeatedly for multiple disease issues - PRV and PRRS elimination are good examples.
Dr. McDowell listed 3 sources of viral introduction threats into negative farms: 1) non-negative new gilt additions; 2) area (aerosol) spread from neighboring farms; and 3) zoonotic spread from personnel incubating human H1N1 or H3N2 influenza.
When a negative farm breaks, Pipestone has the virus sequenced and investigated to the level necessary to definitively characterize it by subtype and origin:
If a swine origin virus, they move immediately to an influenza elimination effort, choosing to return the farm to negative status as soon as possible. One complicating factor Pipestone has discovered in working with some H1N1 isolates is the difficulty in readily determining whether the isolate is of swine or human origin. They have developed excellent working relationships with university influenza researchers who have assisted in single nucleotide polymorphisms (SNP) analyses to definitively determine the viral source as human or swine.
Human origin viruses are interesting. In their experience, most human-origin infections die out on their own without intervention; these viruses in general have not adapted sufficiently to survive in the swine population beyond 3 months with normal elimination pressure. If they do survive in the population beyond 3 months, the herd then undergoes a formal influenza elimination protocol. Pipestone did experience one H1N1 human spillover in 2025 that has maintained itself and remains in the process of eliminating that virus from that multiplier. 3 other human spillovers all resolved spontaneously.
Dr. McDowell shared this summary slide to end her presentation:
I noted with interest the reference to utilizing rapid IAV antigen testing for employees. Here is the commercially available kit: Amazon.com: WELLlife Flu A&B Home Test, Flu Tests for Home 2 Tests. At $7 per test, it’s a bit steep for routine use for screening, but the technology is there now to look for evidence of Flu A in employees in the barn prior to checking in for work with the pigs. Given that people are shedding high levels of influenza virus prior to onset of fever, I’m concerned that our traditional temperature screening for employees is insufficient protection for the pigs. In certain high value operations, combined with high risks for worker illness (high community influenza levels?), POC human testing might be an option on a strictly experimental non-medical use basis for animal risk assessment only.
Keeping a large population of animals negative to an endemic virus in population dense areas with a potentially zoonotic virus carried by caretakers is a tall order! Pipestone is to be commended for moving forward on influenza elimination, making mistakes as fast as possible (as the late Dr. Al Leman (Conference namesake) used to advocate…). [It’s not surprising that Pipestone was in part founded by Dr. Gordon Spronk, one of Dr. Leman’s early students. My contemporaries remember and revere Al and know and admire Gordon!]
New USDA Influenza Surveillance Program Algorithm
Many of you remember my columns discussing the “holes” in the USDA Swine Influenza A Virus Surveillance Program related to testing for H5N1: Swine H5N1 Surveillance: Walk the Talk. Well, as of October 1, USDA has modified the testing algorithm, for a lot of good cost-efficient reasons, with the result that anyone wanting to use the USDA program for funding their diagnosis of positive influenza A samples will have those samples subjected to whole genome sequencing and reporting:
Both the NAHLN labs and NVSL have discontinued use of the subtyping PCR assay on positive Matrix PCR samples, instead moving qualifying positive matrix samples (also with expanded case definitions) directly to Whole Genome Sequencing with subtyping determined as a by-product of the sequencing reads. Producers can still have samples tested (and sequenced) at their own expense as a private swine influenza sample submission, but USDA will no longer pay for Matrix and subtyping PCR testing. In essence, producers will need to decide upfront whether to participate or not in the USDA program, without the “opportunity” to screen for a possible unwelcome H5 finding with the subtyping PCR prior to allowing WGS.
It will be interesting to see what effect the algorithm change has on voluntary participation. My fear is that it could drive sampling away from USDA-subsidized testing to keep results private. I’m not sure what effect that will have on the availability of influenza sequence data in general, since some of the large diagnostic labs may still enter sequences into GenBank individually with private testing. That may also create a legal morass since any lab who happens upon a positive H5 result in pigs through sequencing (USDA surveillance or not) could technically be required to report it and forward the sample to USDA NVSL under the H5 Federal Order. I don’t pretend to know how this will all play out.
To Conclude…
From my perspective the sum of all the information in this column argues strongly for a lot MORE influenza sequence data in pigs, as well as from other species. If/when we find H5 in pigs or other species, we’ll call on experts like those in our swine veterinary and research community to assist in making intelligent risk-based response recommendations, rather than simplistic old-school “depopulate them all” reactions based on limited information.
This ongoing swine influenza applied research narrative proves in spades that not all influenza can or should be handled like HPAI in poultry. In fact, HPAI today should no longer be handled as past HPAI in poultry! We still need to depopulate infected flocks, but pigs (and cattle) have taught us that surveillance needs to be a lot more sophisticated (earlier, targeted, and environmentally based), vaccination has a place in managing outbreak risks, and decision-making needs to be empowered at the local level. And yes, biosecurity is critical, but not exclusively the solution, Secretary Rolland.
The swine industry has really shined in bringing people together to solve problems, sharing data beyond exclusivity limits and collaborating beyond legal requirements. We have reams of swine sequence data driving research conclusions because the industry (and USDA!) were/ are willing to let it go directly to GenBank, and some really talented ARS, CDC, NIH, University, etc., researchers (Amy, Tavis, Martha, Marie, Montse, Phil, Andy and their many cohorts) mined it extremely well. The swine work they accomplished in turn ties into poultry and human influenza virus sequencing results to multiply the rewards. Now, when “novel” H5N1 2.3.4.4b B3.13 struck, we have a large cadre of experts as well as lots of preexisting influenza data ready to apply some lessons learned to a new influenza crisis. Free and open H5N1 data access and wide-open research projects would allow these same folks and others to work their magic once again.
Follow the pigs to find new answers:
Here’s one more fitting piece of advice from an “old-timer” familiar to a few of you other old-timers like me…As former USDA MRPBS Under-Secretary Bill Hawks said in 2004 during the Mad Cow Crisis (and many other times):
“Working Together Works”
John