Thursday, March 07, 2024

Virology: Novel Influenza A Viruses in Pigs with Zoonotic Potential, Chile

 

#17,940

While we watch high profile pandemic contenders like HPAI H5Nx, H7N9, MERS-CoV, Nipah, and `Disease X' with considerable interest, there are scores of `lesser' pandemic threats in the wild that are probably more likely to emerge.

In the spring of 2009, while the world was focused on avian flu, we saw a novel H1N1 virus unexpectedly emerge from swine in Mexico, jump to humans, and begin its world tour.

While younger people were disproportionately affected, the pandemic turned out to be relatively mild, and was declared over by the summer of 2010.

Similar, mild-to-moderate influenza pandemics occurred in 1968 (H3N2) and 1957 (H2N2), while the 1918 H1N1 pandemic represents a far more extreme event. But even relatively mild pandemics are costly, both in terms lives lost and/or disrupted and the global economy.

Since all known influenza pandemics (going back 130 years) have stemmed from H1, H2, or H3 viruses (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?) - subtypes to which pigs are also highly susceptible - the potential for seeing another swine-origin pandemic virus seems substantial.   

Every year we see a dozen or so confirmed swine variant virus spillovers into humans, mostly from North America and Europe, but these cases are thought to be just the tip of the iceberg.  

During a small outbreak of H3N2v (n=13) a dozen years ago, researchers estimated that fewer than 1 in every 200 community cases was identified (see CID Journal: Estimates Of Human Infection From H3N2v (Jul 2011-Apr 2012).

Most known spillovers have produced only mild or moderate illness, although a few deaths have been reported. Unfortunately, routine surveillance, testing, and reporting on swine influenza (both in pigs and in humans) ranges from intermittent to non-existent around the globe.  

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

In 2021 the CDC ranked a Chinese Swine-variant EA H1N1 `G4' as having the highest pandemic potential of any flu virus on their list (see EID Journal: Zoonotic Threat of G4 Genotype Eurasian Avian-Like Swine Influenza A(H1N1) Viruses, China, 2020).

But most of the swine-Influenza A viruses (swIAV) that circulate around the world do so largely under our radar.

Today we've got what is billed as the largest molecular epidemiological study of swine IAV in South America from researchers in Chile.  They report finding a number of novel swine IAVs circulating in Chilean swine to which the local population likely has little or no immunity. 

This, as one would expect, is a lengthy and detailed report.  I've only posted some excerpts, so follow the link to read it in its entirety. 

I'll have a bit more after the break.

Novel influenza A viruses in pigs with zoonotic potential, Chile

Authors: Rodrigo Tapia, Bárbara Brito, Marco Saavedra, Juan Mena, Tamara García-Salum, Raveen Rathnasinghe, Gonzalo Barriga DOI: https://doi.org/10.1128/spectrum.02181-23

PDF/EPUB

ABSTRACT

Novel H1N2 and H3N2 swine influenza A viruses (IAVs) have recently been identified in Chile. The objective of this study was to evaluate their zoonotic potential. We perform phylogenetic analyses to determine the genetic origin and evolution of these viruses, and a serological analysis to determine the level of cross-protective antibodies in the human population.
Eight genotypes were identified, all with pandemic H1N1 2009-like internal genes. H1N1 and H1N2 were the subtypes more commonly detected. Swine H1N2 and H3N2 IAVs had hemagglutinin and neuraminidase lineages genetically divergent from IAVs reported worldwide, including human vaccine strains.
These genes originated from human seasonal viruses were introduced into the swine population since the mid-1980s. Serological data indicate that the general population is susceptible to the H3N2 virus and that elderly and young children also lack protective antibodies against the H1N2 strains, suggesting that these viruses could be potential zoonotic threats. Continuous IAV surveillance and monitoring of the swine and human populations is strongly recommended.

(SNIP)
Novel H1N2 and H3N2 swine IAVs have recently been identified in Chile. The HA genes of these viruses were likely introduced from humans in the past and now are genetically distant from other IAVs identified in swine and humans globally, including commercial vaccine strains used in pigs.

These viruses replicated and were shed, without prior adaptation, in the upper respiratory tract of guinea pigs, which were used to evaluate their infection dynamics (7–9). These findings suggest that these viruses could have public health importance, emphasizing the need to carry out further studies to evaluate the zoonotic potential of these viruses.

Here, we performed a systematic swine and human molecular epidemiological study, analyzing all gene segments to determine the genetic diversity, predominant lineages, and the origins and evolution of swine IAVs circulating in commercial farms in Chile. We also performed a serological analysis to evaluate the presence of cross-reactive antibodies against these swine viruses in the Chilean human population.

          (SNIP)  

Based on these phylogenetic analyses and their results, we proposed a model of the introduction of human influenza viruses into the swine population in Chile leading to the generation of novel swine IAVs, considering potential introduction times and evolution through multiple reassortment events (Fig. 7).

(SNIP)

In summary, we showed that Chilean swine H1N2 and H3N2 viruses likely originated from human seasonal viruses introduced to the swine population multiple times since the mid-1980s. Our results also show that the introduction of human A(H1N1)pdm09 viruses into swine populations generated a series of additional reassortment events that further diversified the swine IAV genotypes and completely displaced the internal genes of the pre-pandemic swine IAV endemic stains. 
Overall, three to four putative reassortment patterns generated eight distinct swine IAV genotypes that circulate in the Chilean swine population today (Fig. 7), which differ from other swine and human IAVs previously reported worldwide. Importantly, our results indicate that the general population is susceptible to the swine H3N2 viruses and that the elderly and young children (<10 years of age) also lack protective antibodies against the swine H1N2 strains, suggesting that these viruses could be potential zoonotic threats.
To date, this is the largest molecular epidemiological study of swine IAV in South America, contributing to global IAV studies in both humans and animals. Continuous surveillance of IAVs circulating in Chilean swine populations and monitoring of workers in the swine industry are necessary and strongly recommended.
Last November the UK reported their first laboratory-confirmed swine variant H1N2v infection (see UKHSA Identifies 1st H1N2v (Swine Variant) Infection In the UK), which raised alarm bells and set off an immediate public health investigation. 

In January the ECDC's journal Eurosurveillance published a Rapid Communications on this event, which describes 1 laboratory confirmed - and two probable - infections that were detected by the UK's epidemiological investigation. 

Although swine variant viruses are generally not efficiently transmitted between humans (until, as we saw in the H1N1 pandemic of 2009, they suddenly are) some limited human-to-human transmission does appear to occur. 

While we've been understandably focused on avian H5Nx viruses the past few months, swine-origin influenza viruses constitute a plausible pandemic threat, are very much worthy of our attention.
A few recent blogs on these viruses include.
Virologica Sinica: The Evolution, Pathogenicity & Transmissibility of Quadruple Reassortant H1N2 Swine Influenza Virus in China

WHO Update & Risk Assessment: H1N1v Case In Brazil

Preprint: Potential Pandemic Risk of Circulating Swine H1N2 Influenza Viruses

JID: Pathogenesis & Transmission Assessment of 3 Swine-origin Influenza A(H3N2) viruses in the U.S. from 2017-2020
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