#17,628
While there are legitimate concerns that an exotic avian influenza virus like H5N1 could adapt to humans, all of the known influenza pandemics over the past 130 years have come from H1, H2, and H3 viruses (see graphic above).Granted, things get a bit murky when you go back past 1918, and there are intriguing hints that an avian (possibly H7) virus might have sparked a epidemic 150 years ago (see Morens and Taubenberger: A New Look At The Panzootic Of 1872).
But recent history suggests that H1, H2, and H3 viruses influenza A viruses - which also circulate in birds, marine mammals, and pigs - have an easier time jumping species to infect humans (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?) than do H5 or H7 viruses.
The 2009 H1N1 pandemic was caused when a swine-origin flu virus - one that had been circulating in pigs for at least a decade - evolved into an easily transmissible strain for humans. While the `mildest' pandemic in a century, it took a heavy toll on kids and young adults.
Every year a small number of `swine-variant' infections are reported in humans in the United States, and around the world, but they undoubtedly occur more often than we know.
Most are mild, or moderate, and while human-to-human transmission has occurred, they are often dead-end infections. But, of course, that could change.
In recent months we've looked at swine variant human infections from Taiwan and Brazil, and the United States. Since 2010, the United States has reported roughly 500 cases, mostly H3N2v.
The CDC's risk assessment for Swine Variant viruses reads:
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
The risk of one of these swine variant viruses sparking a pandemic is relatively low, but it isn't zero. The CDC's IRAT (Influenza Risk Assessment Tool) lists 3 North American swine viruses as having at least some pandemic potential (2 added in 2019).
H1N2 variant [A/California/62/2018] Jul 2019 5.8 5.7 Moderate
H3N2 variant [A/Ohio/13/2017] Jul 2019 6.6 5.8 Moderate
H3N2 variant [A/Indiana/08/2011] Dec 2012 6.0 4.5 Moderate
Yesterday, researchers from the CDC's Influenza Division published a brief report in the JID (Journal of Infectious Diseases) where they characterized three H3N2 swine flu viruses circulating in the United States between 2017 and 2020.
They found that all three viruses replicated well in ferrets (often used as a human surrogate in influenza studies), and were capable of limited airborne transmission. Due to its length, I've only posted some excerpts, so follow the link to read it in its entirety.
I'll have a bit more after you return.Pathogenesis and transmission assessment of three swine-origin influenza A(H3N2) viruses with zoonotic risk to humans isolated in the U.S from 2017-2020
Xiangjie Sun, Jessica A Belser, Joanna A Pulit-Penaloza, Nicole Brock, Claudia Pappas, Natosha Zanders, Yunho Jang, Joyce Jones, Terrence M Tumpey, C Todd Davis ... Show more
The Journal of Infectious Diseases, jiad359, https://doi.org/10.1093/infdis/jiad359
Published:
21 August 2023 Article history
Abstract
The sporadic occurrence of human infections with swine-origin influenza A(H3N2) viruses and the continual emergence of novel A(H3N2) viruses in swine herds underscore the necessity for ongoing assessment of the pandemic risk posed by these viruses. Here, we selected three recent novel swine-origin A(H3N2) viruses isolated between 2017 to 2020, bearing HAs from the 1990.1, 2010.1 or 2010.2 clades, and evaluated their ability to cause disease and transmit in a ferret model.We conclude that despite considerable genetic variances, all three contemporary swine-origin A(H3N2) viruses displayed a capacity for robust replication in the ferret respiratory tract and were also capable of limited airborne transmission. These findings highlight the continued public health risk of swine-origin A(H3N2) strains, especially in human populations with low cross-reactive immunity.
INTRODUCTION
Since 2010, there have been 439 confirmed cases of human infection with swine-origin influenza A(H3N2) variant (v) viruses in the United States, one of which has resulted in death [1]. During this time, A(H3N2)v viruses have exhibited considerable genetic and antigenic variances, necessitating regular updates of risk assessment evaluations and pre-pandemic candidate vaccine strain selection.
Currently, multiple genotypes of influenza A viruses (IAV) of the H3N2 subtype are cocirculating in U.S. swine populations; the dominant circulating viruses include those belonging to the 1990.4, 2010.1 and 2010.2 H3 HA swine clades and 1998 and 2002 N2 NA swine clades (Global H3 HA and N2 NA swine influenza virus nomenclature identifies a clade based on the decade, or year for HA or NA, when its ancestral human seasonal A(H3N2) virus or swine live attenuated vaccine strain first spilled over to swine and established sustained transmission in pigs) [2, 3]. Since their introduction, the major HA and NA clades of swine A(H3N2) virus have further evolved in swine hosts, splitting into statistically supported monophyletic clades; e.g., N2.2002A and 2002B [4].
(SNIP)
With regard to virus transmission, all three swine-origin A(H3N2) viruses transmitted efficiently via direct contact, with contact ferrets shedding virus with similar peak viral titers and kinetics on day 3-9 post contact (p.c.) as inoculated ferrets; all contact ferrets from these experiments seroconverted to homologous virus (Fig 1 & Table 2).
Furthermore, all three viruses exhibited a limited capacity for transmission by respiratory droplets. One of three contact ferrets in each virus group became productively infected, as evidenced by detection of infectious virus in NW specimens on day 3 p.c. with subsequent seroconversion to homologous virus; one additional contact ferret in both OH/17 and SW/OK/17 virus groups also exhibited seroconversion by day 21 p.c. in the absence of infectious virus detection ( Fig 1 and Table 2).
(SNIP)
Taken together, our study confirms that robust viral replication and a limited ability to spread by the airborne route are associated with newly emerged swine A(H3N2) viruses. Although the HA of these viruses is descendant from human seasonal H3 virus, their evolution in swine may take a pathway different from the A(H3N2) viruses in humans.
Considering differences in seroprotection rates against historic H3N2 viruses across the human population [12, 15], the public health threat posed by swine influenza viruses cannot be ignored. Continued swine influenza virus surveillance and risk assessment of contemporary IAV at the swine-human interface are essential for pandemic preparedness.
Taken individually, the odds that any single novel flu virus (H5N1, H5N6, H3N2v, H1N2v, H10N8, H3N8, etc.) will spark the next pandemic is very low. If if were easy for nature to cobble together a biologically `fit' pandemic virus, we'd be hip deep in pandemics all the time.
Two summers ago - before the global surge in H5N1 - researcher writing in PNAS Research: Intensity and Frequency of Extreme Novel Epidemics suggested that the probability of novel disease outbreaks will likely grow three-fold in the next few decades.But it does seem as if there are more opportunities today for a pandemic to emerge, with unprecedented levels of zoonotic viruses spreading globally, and spilling over into new hosts (pigs, mink, foxes, marine mammals, etc.).
