#17,272
While avian H5N1 is currently viewed as the most concerning new pandemic threat (and with good reason), it isn't the only potential candidate out there. The CDC tracks no less than 23 novel flu subtypes with pandemic potential (see IRAT List below).
The flu virus with the highest emergence score (as of 2020) was an EA H1N1 virus circulating in swine in China (see EID Journal: Zoonotic Threat of G4 Genotype Eurasian Avian-Like Swine Influenza A(H1N1) Viruses, China, 2020).
In second place (in terms of likelihood of emergence) is a North American Swine Variant H3N2v [A/Ohio/13/2017] which was added in 2020, which joins 2 other North American Swine flu viruses (H1N2 variant [A/California/62/2018] and H3N2 variant [A/Indiana/08/2011]).
This list is only of influenza viruses thought to have pandemic potential, and does not include other threats, such as coronaviruses (i.e. MERS-CoV), or zoonotic pathogens like Nipah, Langya, or Ebola.
Although we see sporadic cases of swine flu viruses jumping to humans in North America, and around the world, surveillance and testing is ranges from poor to non-existent, and so these type of infections are likely far more common than we know.
The CDC's risk assessment for Swine Variant viruses reads:
Since the influenza subtypes that commonly circulate in swine (H1, H2 & H3) are also the same HA subtypes that have caused all of the human influenza pandemics going back 130 years (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?), swine influenza viruses are watched carefully for signs of jumping to humans.Sporadic infections and even localized outbreaks among people with variant influenza viruses may occur. All influenza viruses have the capacity to change and it’s possible that variant viruses may change such that they infect people easily and spread easily from person-to-person. The Centers for Disease Control and Prevention (CDC) continues to monitor closely for variant influenza virus infections and will report cases of H3N2v and other variant influenza viruses weekly in FluView and on the case count tables on this website
All of which brings us to a recent study, published in the journal Viruses, that identifies several swine H3N2 strains that have evolved to be able to transmit to ferrets, and which likely evade current immunity and vaccines, making them a rising threat to public health.
I've only included the Abstract and some excerpts from the study, so follow the link to read it in its entirety. I'll have a brief postscript when you return.
Swine-to-Ferret Transmission of Antigenically Drifted Contemporary Swine H3N2 Influenza A Virus Is an Indicator of Zoonotic Risk to Humans
by
Carine K. Souza 1, J. Brian Kimble 1,†,Tavis K. Anderson 1, Zebulun W. Arendsee 1,David E. Hufnagel 1,Katharine M. Young 1,Phillip C. Gauger 2,Nicola S. Lewis 3,C. Todd Davis 4,Sharmi Thor 4 and Amy L. Vincent Baker 1,*
Viruses 2023, 15(2), 331; https://doi.org/10.3390/v15020331
Received: 8 December 2022 / Revised: 21 January 2023 / Accepted: 22 January 2023 / Published: 24 January 2023
Abstract
Human-to-swine transmission of influenza A (H3N2) virus occurs repeatedly and plays a critical role in swine influenza A virus (IAV) evolution and diversity. Human seasonal H3 IAVs were introduced from human-to-swine in the 1990s in the United States and classified as 1990.1 and 1990.4 lineages; the 1990.4 lineage diversified into 1990.4.A–F clades. Additional introductions occurred in the 2010s, establishing the 2010.1 and 2010.2 lineages.Human zoonotic cases with swine IAV, known as variant viruses, have occurred from the 1990.4 and 2010.1 lineages, highlighting a public health concern. If a variant virus is antigenically drifted from current human seasonal vaccine (HuVac) strains, it may be chosen as a candidate virus vaccine (CVV) for pandemic preparedness purposes.We assessed the zoonotic risk of US swine H3N2 strains by performing phylogenetic analyses of recent swine H3 strains to identify the major contemporary circulating genetic clades. Representatives were tested in hemagglutination inhibition assays with ferret post-infection antisera raised against existing CVVs or HuVac viruses.The 1990.1, 1990.4.A, and 1990.4.B.2 clade viruses displayed significant loss in cross-reactivity to CVV and HuVac antisera, and interspecies transmission potential was subsequently investigated in a pig-to-ferret transmission study. Strains from the three lineages were transmitted from pigs to ferrets via respiratory droplets, but there were differential shedding profiles.These data suggest that existing CVVs may offer limited protection against swine H3N2 infection, and that contemporary 1990.4.A viruses represent a specific concern given their widespread circulation among swine in the United States and association with multiple zoonotic cases.
(SNIP)
Swine IAVs are considered a threat to public health due to swine populations worldwide harboring a vast array of antigenically diverse IAVs that occasionally spill over into humans. Consequently, swine-origin variant virus cases in humans have raised public health concerns, and there is a critical need to assess the zoonotic potential of these viruses before swine-to-human epidemics or pandemics occur [32].Zoonotic interspecies IAV transmission requires important factors, such as virus adaptation, exposure of a susceptible human, virus load, and close contact with infected swine that increases the risk of infection [33,34,35,36]. The US CDC have reported variant cases since 2005, with most cases identified in individuals (mainly children) at swine exhibitions who had close contact with swine at agricultural fairs. Within this period, H3N2v virus infections have been the most frequently detected in the U.S. [32].Although person-to-person transmission of variant viruses is rare, variants have the potential to evolve and may acquire the ability to transmit from human-to-human, as occurred with the H1N1pdm09 [37]. In response to the recognition of the public health risk of swine IAV, human pandemic preparedness efforts have expanded to include the characterization of swine-origin variant strains and, when appropriate, the development of CVV. However, the genetic and antigenic diversity of swine H3 clades [18,38] requires regular characterization to identify swine IAV that represent a pandemic threat.Here, we identified U.S. swine H3N2 lineages with zoonotic potential based on the loss of cross-reactivity of post-infection ferret antisera raised to relevant CVV or human seasonal vaccines with an integrated assessment using an interspecies swine-to-ferret transmission model.
(SNIP)
Both 1990.4.A and 1990.4.B.2 clades replicated efficiently in the respiratory tract of pigs and transmitted high virus titers in nasal washes to contact ferrets, as confirmed by seroconversion of contact ferrets at 12 dpc. A previous ferret-to-ferret transmission study with an H3N2v virus demonstrated that high virus shedding titers in ferret nasal washes correlated with high growth in human airway epithelial cells, suggesting that these viruses can infect cells of the human airway [42]. Although the body weight and temperature were not significantly different in ferrets infected with all the viruses we tested, the 1990.4.A and 1990.4.B.2 contact groups displayed a trend of weight loss or no weight gain when virus shedding was detected.(SNIP)
Taken together, our study indicated that the swine H3 1990.1, 1990.4.A, and 1990.4.B.2 clades are a zoonotic risk as they displayed reduced cross-reactivity with ferret antisera raised to human seasonal vaccines and/or CVVs and transmitted from pig-to-ferrets.
Our findings suggest that existing CVVs should be updated to reflect contemporary swine IAV diversity; specifically, we suggest that the 1990.4.A clade that is widespread in U.S. swine populations and that has previously caused a significant number of H3 variant human cases requires revision. In addition, our study suggests that minor swine IAV clades that are regularly detected in US swine populations have zoonotic potential and should be considered in risk assessments of swine H3N2 IAV for pandemic preparedness strategies.
Pigs are one of the most commonly raised food animals in the world, accounting for somewhere between 700 million and 800 million head at any given time. Swine surveillance, and testing for swine flu viruses is limited - even in places like the United States - and nonexistent in much of the world.
Complicating matters, swine are unusually susceptible to a wide variety of flu viruses, including avian flu (see Sci. Rpts.: Evidence Of H5N1 Exposure In Domestic Pigs - Nigeria), swine flu and human flu strains. Pigs are considered excellent `mixing vessels' for influenza, and have the potential to churn out new, and unpredictable, subtypes.
While an H3N2 swine variant pandemic might not be as severe as an H5Nx avian flu pandemic, H3 (or H1) swine viruses likely have less far to evolve to become a genuine pandemic threat.
It happened in 2009, and all of the ingredients appear to be out there to allow it to happen again.
