If an H5 virus is spreading in pigs then it really is code red.
Factory Farming
Keeping large quantities of pigs susceptible to influenza in crowded conditions is a risk from a public health perspective. The pigs could enable long chains of infection, leading to more selection pressure. Not vaccinating all pigs with available swine influenza vaccine is further increasing the risk. So far, pigs were only involved in the 2009 H1N1 pandemic, but this may change.
At 26 storeys it is by far the biggest single-building pig farm in the world, with a capacity to slaughter 1.2 million pigs a year.
Our last pandemic, swine flu in 2009, arose not from some backwater wet market in Asia, however. It was largely made-in-the-USA on pig production operations in the United States. In this new Age of Emerging Diseases, there are now billions of animals overcrowded and intensively confined in filthy factory farms for viruses to incubate and mutate within. Today’s industrial farming practices have given viruses billions more spins at pandemic roulette.
Regarding the segments found per sample, the simultaneous presence of segments from both subtypes was much lower in vaccinated animals, indicating that the vaccine reduced the likelihood of genomic reassortment events. (...) The present study further emphasized the vast evolutionary capacity of swine IAV, under natural infection and vaccination pressure scenarios.
We assessed postchallenge viral shedding in market-age swine vaccinated with either live-attenuated influenza virus (LAIV), killed influenza virus (KV), or sham vaccine (NV). (...) Ferrets exposed to vaccinated pigs had lower cumulative virus titers in nasal wash samples (...) and experienced reduced clinical signs during infection. Our findings support the implementation of preexhibition influenza vaccination of swine to reduce the public health risk posed by IAV-S at agricultural exhibitions.
This situation in humans contrasts markedly with that in pigs. Although influenza in people is largely seasonal, occurring mostly during winter, swine flu in pigs is not seasonal and can occur year-round. So, while human influenza is controlled using a single vaccination administered at the start of the flu season in autumn, the recommendation for pigs is to vaccinate sows every four months.
Pig farmers and their vets are often hesitant to follow recommendations for mass vaccination of their herds on the grounds that they consider this to be too expensive.
While it is true that vaccines cannot totally eliminate virus, they prevent clinical disease and significantly reduce the amount of virus in circulation, thereby reducing the opportunity for viruses to mix, exchange genetic material and emerge as new, potentially pandemic strains. Vaccines against swine flu for pigs are much more effective in preventing clinical disease than flu vaccines used in people. It is therefore ironic that the widespread use of the vaccines in people is widely accepted, while the use of much more effective vaccines in pigs is sometimes questioned.
The global population of pigs has grown steadily over the past decades, from around 400 million in the early 1960s to close to one billion today. At the same time, the average size of pig farms has also increased. Throughout the world, small, backyard pig production has given way to large, commercial pig units.
Whereas in the 1990s a large pig farm would have 200 breeding sows, now many farms have thousands or even tens of thousands of sows.
In Europe, WIV vaccines are generally administered only to sows, yet only 10–20% of the sow population is vaccinated.
In North America, vaccination against IAV-S is used more than in the EU with ~70% of the pig population being vaccinated.
The risk for reassortment of the HPAI H5N1 2.3.4.4b lineage with endemic swine IAV is a consideration on the basis of the susceptibility to this lineage demonstrated in our study, the prevalence of IAV infection and comorbidities in swine herds, and animal husbandry practices. However, the risk for incursion is likely lower in confinement operations with industry standard biosecurity than for backyard or feral pigs. Birdproofing feed and facilities, avoiding the use of untreated water, and restricting peridomestic scavenger mammals from premises are measures to increase biosecurity against HPAI H5N1 clade 2.3.4.4b virus incursion into swine herds.
Poultry Litter
Poultry litter consists mostly of poultry excrement and is used as feed for livestock.
Deep in the remote Maili Kumi Location in Buuri, Meru County, a state of the art chicken farm is thriving. Here, you can catch a glimpse of an unlikely friendship that has made the farm a household name among residents. The farm rears about 20,000 chicken in automated cages laying on a one-acre farm. “We have around 92 pigs, so the relationship between the pigs and chicken, is that the pigs consume poultry waste,” said (...), the farm manager.
The economics of production results obtained showed that it was more economical to raise pigs using broiler litter at 20% of the diet. The results obtained from this study showed that processing methods such as ensiling, composting and sun-drying improved the nutrient composition of broiler litter and more over, processed broiler litter can be included up to 20% in the diet of growing pigs without any deleterious affect on the performance, hematological indices and economics of production in the diet of growing pig in the tropics. (...) For the test ingredient, the crude protein which was affected by processing (p< 0.05) ranged from 19.2% to 26.9%. Unprocessed broiler litter had the lowest value while highest value occurred with ensiled broiler litter.
Mixing Vessels
Pigs are generally susceptible to influenza virus infections, are farmed in large numbers, and their airways contain a large number of both receptor types associated with birds and mammals. A study in Indonesia during a H5N1 outbreak documented 7.4% of all tested pigs to be infected with H5N1. The pigs showed no symptoms, making outbreaks hard to detect. However, the lack of symptoms may also reduce the individual pig-to-human transmission and pig-to-pig transmission risk. Additionally, it proved difficult to actually infect pigs with H5N1 clade 2.3.4.4b.
Influenza viruses have an eight-segment genome. Each segment can potentially swap genes with other influenza viruses inside a host, a process known as reassortment. This, Schaffner told Al Jazeera, makes minks and swine — which can contract human, swine, and avian influenza viruses — potential mixing bowls.
Swine contain an abundance of both α2,3 and α2,6 SA in their respiratory tract (...) and therefore are considered to be a potential “mixing vessel” for human, avian, and other swine influenza strains (...). In previous studies using enzymatically modified erythrocytes, swine viruses have shown a preference for α2,6 SA binding (...), and it is generally believed for an avian or swine influenza strains to infect humans and transmit efficiently from person to person, it must first be able to bind α2,6 SA(...).
Chairul Nidom of Airlangga University in Surabaya, Indonesia, and colleagues in Japan, have been tracking H5N1 in pigs since 2005 in Indonesia, the country hardest hit by the avian flu virus. They now report that between 2005 to 2007 when the avian flu peaked, 7.4 per cent of 700 pigs they tested also carried H5N1. There have been sporadic reports of H5N1 in pigs, but this is the first time the extent of the problem has been measured.
One isolate had acquired the ability to recognize a human-type receptor. No infected pig had influenza-like symptoms, indicating that influenza A (H5N1) viruses can replicate undetected for prolonged periods, facilitating avian virus adaptation to mammalian hosts. Our data suggest that pigs are at risk for infection during outbreaks of influenza virus A (H5N1) and can serve as intermediate hosts in which this avian virus can adapt to mammals.
Interspecies transmission of avian influenza virus (AIV) to pigs was reported in Canada in 1999 for a low pathogenic H4N6 virus, followed by reports of an H3N3 and H1N1 strain in Ontario in 2001. So far, the large majority of AIV transmissions to swine have occurred in China, including low-pathogenicity AIV of the H9N2, H7N9, H1N5, H4N1, H6N6 and H4N8 subtypes. In addition, H5N2, H7N2 and H9N2 viruses were reported in South Korean pigs in 2001, 2004 and 2008, respectively. Genomes of highly pathogenic H5N1 viruses were also reported in Indonesian pigs in the 2005–2007 period. More recently, in 2018, the genome of an H5N2 virus was reported in Mexican pigs.
While the swine nasal swabs were all RT-PCR negative for the influenza type A matrix (M) gene, the majority (%) of the tested pigs resulted serologically positive for the hemagglutination inhibition test and microneutralization assay, using an H5N1 strain considered to be homologous to the virus detected in the farm.
Pigs constitute a mixing vessel of IAV from different species including avian and human hosts. However, other host species such as turkey and quail but also humans themselves may also act in this way; thus, pigs are not essentially required for the generation of IAV reassortants with a multispecies origin.
In conclusion, only 1 of 8 pigs inoculated intranasally with HPAI virus H5N1 underwent transient, low-level infection that resulted in the presence of viral RNA in several tissue specimens and seroconversion at 14 dpi. In naturally infected wild mammals, this virus was prominently detected in the brain (2). Given the detection of viral RNA in the brain of 1 intranasally inoculated pig, it cannot be excluded that longer observation might have revealed continuing viral replication in the brain of this animal.
“That is the last barrier,” Beer says. Although MxA’s detection skills appear very weak in ferrets and some other animals, it is more sensitive in humans—and in pigs. “If an H5 virus is spreading in pigs then it really is code red,” Beer says.
In an unpublished experiment Beer and his colleagues infected pigs with H5N1. Even when high doses were used, the virus barely replicated in the animals.
Both mammal isolates evaluated in this study contained the PB2 E627K mutation, were detected in the noses of inoculated pigs, and transmitted to >1 contact pig. The PB2 gene of all human seasonal viruses of the 20th Century contain K627, whereas most clade 2.3.4.4b viruses detected in birds in 2022–2023 contain E627, supporting the role of that mutation in mammalian adaptation. Although we did not fully evaluate the direct effects of the E627K mutation in swine, the shedding and transmission profile shown for the 2 mammal isolates in this study indicate this adaptive mutation might have increased viral fitness through enhanced polymerase activity to enable transmission in an otherwise less susceptible host.
H9 subtype was not detected from serum samples collected in 2003, however, 4.7 % and 8.2 % of H5 subtype influenza positive were detected from serum samples which collected from Guangdong and Fujian provinces.
In contrast, we detected A/raccoon/WA/22 in the nasal cavity of inoculated pigs (4 of 15) and transmitted to contacts (2 of 5). Similarly, we detected A/redfox/MI/22 in the nasal cavity of inoculated pigs (5 of 15) and transmitted to a single contact.
Swine have presented an attractive explanation for how avian viruses overcome the substantial evolutionary barriers presented by different cellular environments in humans and birds. However, key assumptions underpinning the swine mixing-vessel model of pandemic emergence have been challenged in light of new evidence. Increased surveillance in swine has revealed that human-to-swine transmission actually occurs far more frequently than the reverse, and there is no empirical evidence that swine played a role in the emergence of human influenza in 1918, 1957, or 1968. Swine-to-human transmission occurs periodically and can trigger pandemics, as in 2009. But swine are not necessary to mediate the establishment of avian viruses in humans, which invites new perspectives on the evolutionary processes underlying pandemic emergence.
Our results suggest that the 1918 pandemic virus originated shortly before 1918 when a human H1 virus, which we infer emerged before ∼1907, acquired avian N1 neuraminidase and internal protein genes. We find that the resulting pandemic virus jumped directly to swine but was likely displaced in humans by ∼1922 by a reassortant with an antigenically distinct H1 HA. Hence, although the swine lineage was a direct descendent of the pandemic virus, the post-1918 seasonal H1N1 lineage evidently was not, at least for HA.
This study aimed to evaluate the pathogenicity and transmissibility of a mink-derived clade 2.3.4.4b H5N1 HPAIV isolate from Spain in pigs. Experimental infection caused interstitial pneumonia with necrotizing bronchiolitis with high titers of virus present in the lower respiratory tract and 100% seroconversion. Infected pigs shed limited amount of virus, and importantly, there was no transmission to contact pigs. Notably, critical mammalian-like mutations such as PB2-E627K and HA-Q222L emerged at low frequencies in principal-infected pigs. It is concluded that pigs are highly susceptible to infection with the mink-derived clade 2.3.4.4b H5N1 HPAIV and provide a favorable environment for HPAIV to acquire mammalian-like adaptations.
H1N1 Swine Flu and Triple-Reassortment
The A(H1N1) [A/swine/Shandong/1207/2016] claims the top spot in the CDC IRAT risk assessment, followed by a human H3N2 virus. H3N2 viruses are quite common in pigs. Both H1N1 and H3N2 viruses are common during human influenza season.
While there are distinctions between human influenza viruses and swine influenza, the characteristics of influenza viruses tend to blur those lines. The evolution of influenza viruses is incredibly complex with repeated inter-species transmission, mutations, and reassortment events. The H1N1 virus which caused the relatively mild 2009 pandemic contained RNA from human influenza, avian influenza, and swine influenza. This is called triple-reassortment. With multiple triple-reassortment events recorded, the abundant prevalence of influenza viruses in swine, including H5N1, the question is why our situation is not worse. An inhibiting factor seems to be that humans tend to infect swine, but swine-to-human transmission is rare.
The 2009 H1N1 virus contains a unique combination of swine, avian, and human influenza virus genes. (...) During this time, reassortment events resulted in the emergence of multiple strains and subtypes (H1N1, H3N2, and H1N2) of triple-reassortant swine influenza viruses with genes derived from human, swine, and avian viruses.
Between September 2018 and December 2019, 1691 swine nasal swabs were collected and tested. Influenza A virus was detected in 30.7% (520/1691), and A/H1N1pdm09 virus was the most commonly identified subtype with 38.07% (198/520), followed by A/H1N2 (16.3%) and A/H3N2 (5.2%).
The data, published in Molecular Therapy – Methods and Clinical Development, indicate that the sa-mRNA influenza vaccine candidates produced a potent, cross-reactive immune response against pandemic and seasonal influenza strains, A(H5N1) and A(H1N1).
The evolutionary genetics of swine influenza viruses are complex; this is the result of numerous cross-species transmissions, introductions, and reassortment events occurring independently in different continents.
A particular strain of swine flu was first recorded in people in 2009. Since then, humans have passed the strain to pigs at least 370 times in the US
Swine-to-human IAV transmissions occurred rarely and mainly sporadically as compared to avian-to-human spill-over events of avian IAV. Yet, new swIAV variants that harbor zoonotic components continue to be detected. This increases the risk that such components might eventually reassort into viruses with pandemic potential. (...) Domestic pig populations should not be globally stigmatized as the only or most important reservoir of potentially zoonotic IAV.
Ultimately, the limited extent of genomic surveillance for IAVs in local swine and
poultry populations constrained our ability to identify a local source for the outbreak. It also
restricted our ability to assess the plausibility of different transmission routes. Although IAV is a
reportable disease in swine and poultry in BC, the passive nature of surveillance programs
combined with the potential for asymptomatic or unremarkable infections means that under-
reporting and under-detection is likely. Indeed, only 4 contemporaneous, local swine-origin
H3N2 IAV genomes were available for analysis, opportunistically detected through an unrelated
research study, and these viruses were not related to the mink farm outbreak. This suggests that
IAV diversity within swine populations is under-characterized. This was further indicated by
limited detections of IAVs with the same genome constellation as far afield as Iowa, Minnesota,
Missouri, and Ontario. This suggests that this IAV reassortant was able to disseminate across
North America largely unnoticed. The uncomfortable corollary is that many other reassortant
IAVs are likely emerging and disseminating unobserved within large, transnational, commercial
swine populations.
