#18,466
Long before HPAI H5N1 unexpectedly spilled over into cattle/goats/alpacas a little over a year ago, there had been worrisome signs and dire warnings about the potential for H5Nx to infect swine, and potentially reassort with other influenza A viruses.
While surveillance has been limited, over the past 20 years we've seen a number of examples of H5N1 infection in pigs, including:
WHO H5N1 detected in pigs in China (2004)
EID Journal: Asymptomatic H5N1 In Pigs (2010)
An Unusual Report Of H5N1 in Pigs (Indonesia 2016)
Sci. Rpts.: Evidence Of H5N1 Exposure In Domestic Pigs - Nigeria (2018)
Two years ago, in EID Journal: Low Susceptibility of Pigs against Experimental Infection with HPAI Virus H5N1 Clade 2.3.4.4b, researchers from Germany's FLI reported on the experimental infection of pigs with an H5N1 clade 2.3.4.4b (genotype Ger-10.21-N1.5) virus.
Reassuringly they found that exposed pigs demonstrated only a low susceptibility to infection with the virus strain used, but they warned:
While that study was going to press, a report came out of Italy of an H5N1 spillover event at a `mixed species' farm (poultry & swine) in Italy, and the subsequent seroconversion of the majority of the pigs tested on that farm (see Study: Seroconversion of a Swine Herd in a Free-Range Rural Multi-Species Farm against HPAI H5N1 2.3.4.4b Clade Virus).However, considering the ongoing massive panzootic of this virus, a plethora of new genotypes of the circulating strain is emerging, with possibly higher permissiveness for pigs.
Once again, swine showed mild or subclinical signs of infection - and little or no detectable virus replication in the nasal cavity. While good news for the pig, it can make it challenging to identify spillover events without serological testing.Last fall H5N1 was detected in two pigs on a farm in Oregon - not from the bovine B3.13 genotype - but rather from a D1.2 genotype reported in poultry. Both pigs were euthanized, and no further spread was detected.
Confirming once again that pigs are moderately susceptible to infection from this genotype, but that they aren't yet able to transmit the virus efficiently to other pigs.
The concern is, that could change. There are more than 100 genotypes of H5N1 circulating in North America, hundreds more around the globe, and new ones continue to emerge.
So far, only 2 (B3.13 and D1.1) have been identified in cattle, but last year's report from Germany: FLI Statement On Experimental Infection Of Dairy Cows With European H5N1 Virus showed other genotypes could infect cattle as well.
And other genotypes and clades have certainly infected pigs, horses, and even sheep over the years.
All of which bring us to a new preprint - published this week on Nature Portfolio - from researchers at NIAID/NIH and the College of Veterinary Medicine, Kansas State University, which demonstrates limited transmission of the Bovine B3.13 genotype of H5N1 in pigs.
I've reproduced the abstract and some excerpts from the full report below, but you'll want to follow the link to read it in its entirety. I'll have a postscript after you return.
Bovine Derived Clade 2.3.4.4b HPAI H5N1 Virus Causes Mild Disease and Limited Transmission in Pigs
Heinz Feldmann, Kyle Rosenke, Trenton Bushmaker, Amanda Griffin, and 17 more
This is a preprint; it has not been peer reviewed by a journal.
https://doi.org/10.21203/rs.3.rs-6567595v1
This work is licensed under a CC BY 4.0 License
Abstract
Highly pathogenic avian influenza virus (HPAIV) H5N1 clade 2.3.4.4b emerged in dairy cows in the United States in early 2024. Since then, this clade simultaneously circulates in wild birds, cattle and poultry with ongoing transmission into several mammalian species. Given the historical role of swine in influenza ecology, susceptibility of pigs to this virus is critical for animal and public health.To address this concern, Sinclair nanopigs were infected with a bovine clade 2.3.4.4b HPAIV H5N1 isolate by combined intranasal, intratracheal and oral administration mimicking possible natural exposure routes. Pigs were productively infected developing either subclinical or mild disease with seroconversion. Virus replication occurred mainly in respiratory tissues resulting in shedding from upper respiratory tract mucosae. Limited transmission to naïve contact cage mates was documented in a subset of transmission pairs.The combination of subclinical clade 2.3.4.4b HPAIV H5N1 replication and limited transmission draws an alarming scenario for One Health considering pigs are a favorable influenza mixing vessel enabling mammalian adaptation.
(SNIP)The epidemiology of influenza A virus infections in swine raises questions to what role pigs could play in the current clade 2.3.4.4b HPAIV H5N1 outbreak on dairy and poultry farms. To assess the potential risk, we infected pigs with a recent bovine clade 2.3.4.4b HPAIV H5N1 (B3.13) isolate (A/bovine/OH/B24OSU342/2024) and demonstrated susceptibility with subclinical or mild disease progression.Virus replication was transient and mainly limited to respiratory tissues with shedding from the oral and nasal cavities. Importantly, infected pigs were able to transmit bovine H5N1 to a limited number of naïve sentinel pigs as evidenced by seroconversion.
Pigs are a natural host of influenza A viruses and express receptors for both mammalian and avian influenza A viruses allowing for the generation of reassortant viruses in case of co-infections and for mammalian adaptation of avian influenza viruses through critical point mutations 28.
Interspecies transmission between humans and pigs have been reported and are often facilitated by a close interaction in agricultural settings such as agricultural fairs and backyard farming 29. Pigs played a critical role in the 2009 H1N1 pandemic by generating a reassortant virus that caused an estimated 0.7 to 1.4 billion human infections world-wide 30 resulting in an approximated 284,000 deaths 31,32.
The detection of infected pigs on a noncommercial farm in Oregon, United States, has shown in principle that pigs are susceptible to natural infection with clade 2.3.4.4b HPAIV H5N1 11. Our study and a recently parallel performed study 33 provide experimental support for the susceptibility of pigs to clade 2.3.4.4b HPAIV H5N1 associated with intermittent low-level virus shedding. Transmission to naïve contact pigs was demonstrated in our study but not by Kwon and colleagues 33. Overall, the susceptibility and occasional transmission of clade 2.3.4.4b H5N1 viruses in pigs is a worrisome scenario for animal and public health
(SNIP)
In conclusion, we have demonstrated that pigs are susceptible to bovine-derived clade 2.3.4.4b HPAIV H5N1 infection resulting in subclinical or mild disease and self-limiting virus replication largely in respiratory tissues. Interestingly, virus shedding from the upper respiratory tract resulted in transmission to contact cage mates.
These findings are of One Health importance as pigs are susceptible to both avian and mammalian influenza viruses increasing the risk for reassortants through co-infections and for mammalian adaptation.
Swine, while highly susceptible to a wide variety of (avian, human, swine) influenza A viruses, are often able to carry these viruses with little or no clinical signs. Every year we see reports of `healthy' looking pigs at fairs and exhibits spreading swine variant viruses to humans (see CDC FluView Week #37: 2 Additional Novel Flu Infections (H3N2v) in Minnesota).
One study (see Asymptomatic Pigs: Revisited) found more than 80% of the pigs that tested positive for influenza at the Ohio State fair between 2009 and 2011 showed no outward signs of illness.
Our USDA’s Influenza A Virus in Swine (IAV-S) Surveillance Program is voluntary, and we've seen reluctance on the part of pig farmers to have their herds tested (see Swine Flu: Don’t Test, Don’t Tell).Although veterinarians often submit respiratory samples to testing labs in response to clinical signs, those signs are often absent in IAV infected swine. It therefore requires a bit of luck - and excellent timing - to detect novel flu viruses in swine.
So far there is no evidence of widespread H5N1 in swine, but the H1N1 virus that sparked the 2009 pandemic spread - largely unnoticed - for a decade in North American pigs before it suddenly acquired the ability to spread efficiently in humans.
A reminder of how quickly the status quo can change.
