#18,261
While there are continued concerns over H5, H7, H9, and even H10 influenza A viruses, as far back as we can go (> 100 years), all known human influenza pandemics have come from H1, H2, or H3 viruses (see ECDC chart below).
As we've discussed previously (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?), what happened prior to 1900 is pretty murky, but the pattern over the past 130 years appears to have been H2, H3, H1, H2, H3, H1, H1 . . . .
Assuming this pattern holds - and a novel H5 or H7 virus doesn't intervene - then we might expect to see an H2 or H3 virus emerge next.
At least twice in my lifetime (1957 & 1968) an avian flu virus has reassorted with the current seasonal flu, to produce a new pandemic virus.
- The first (1957) was H2N2, which according to the CDC `. . . was comprised of three different genes from an H2N2 virus that originated from an avian influenza A virus, including the H2 hemagglutinin and the N2 neuraminidase genes.'
- In 1968 an avian H3N2 virus emerged (a reassortment of 2 genes from a low path avian influenza H3 virus, and 6 genes from H2N2) which supplanted H2N2 - killed more than a million people during its first year - and continues to spark yearly epidemics more than 55 years later.
While we could seen an H1, H2, or H3 virus emerge from swine, marine mammals, horses, or even dogs, the biggest and most dynamic reservoir are birds. And for a variety of reasons, China continues to be a fertile breeding ground for viral reassortment (see Rocking The Cradle Of Influenza).
Over the past 12 months we've seen a number of reports, and studies, on several worrisome H3Nx reassortant viruses coming out of Mainland China, including:
Transboundary & Emerg. Dis.: H3 Avian Influenza Virus Isolated from China in 2021–2022 Showed the Emerging H3N8 Posed a Threat to Human Health
One Health Adv.: Surveillance & Characterization of Avian-origin H3N2 Canine Influenza Viruses (China 2021)
Frontiers Microbiology: China's Growing Concerns Over The H3 AIV
Emerg. Microb & Inf.: Emergence of Novel Reassortant H3N3 Avian Influenza viruses, China 2023
A Novel Triple Reassortment H3N8 Avian Influenza Virus: Characteristics, Pathogenicity, and Transmissibility
Today we can add another, which discusses the first detection of a novel H3N2 reassortant virus in Northern China (one which was previously reported in poultry in Jiangsu Province).
This reassortant is concerning since its HA comes from the H3N8 virus which has spilled over into humans at least 3 times in recent years, its NA comes from the H10N3 virus which has also infected humans, and its internal genes are from the H9N2 virus, which has infected > 130 people over the past 2 decades.
The fact that it has now been found in Northern China suggests it may have been carried in by migratory birds. In addition to this novel H3N3 virus, this survey found many of the `usual suspects' (H3, H5, H7, H9, etc.) among the 6,000 samples analysed.
Due to its length, I've only posted the abstract and a few excerpts. Follow the link to read the report in its entirety. I'll have a postscript after the break.
Surveillance of avian influenza viruses in Hebei Province of China from 2021 to 2023: identification of a novel reassortant H3N3
Yanbai Li 1, Zhe Yin 1, Juan Wang 1, Feng Li 3, Peng Liu 4, Fei Yu 5
Open Access Published:August 20, 2024 DOI:https://doi.org/10.1016/j.jinf.2024.106240
Highlights
• A novel reassortant H3N3 virus was identified, for the first time, in Northern China.
• The currently predominant subtypes of AIVs have been isolated from Hebei region.
• AIVs may have infected local poultry, posing potential risk of transmission to human.
• These isolates may share a common ancestor with the Yellow River Basin isolates.
Abstract
Avian influenza remains a global public health concern for its well-known point mutation and genomic segment reassortment, through which plenty of serum serotypes are generated to escape existing immune protection in animal and human populations. Some occasional cases of human infection of avian influenza viruses (AIVs) since 2020 posed a potential pandemic risk through human-to-human transmission. Both east-west and north-south migratory birds fly through and linger in the Hebei Province of China as a stopover habitat, providing an opportunity for imported AIVs to infect the local poultry and for viral gene reassortment to generate novel stains.
In this study, we collected more than 6,000 environmental samples (mostly feces) in Hebei Province from 2021 to 2023. Samples were screened using real-time RT-PCR, and virus isolation was performed using the chick embryo culture method. We identified 10 AIV isolates, including a novel reassortant H3N3 isolate. Sequencing analysis revealed these AIVs to be highly homologous to those isolated in the Yellow River Basin. Our findings supported that AIVs keep evolving to generate new isolates, necessitating a continuous risk assessment of local avian influenza in wild waterfowl in Hebei, China.
Identification of the first H3N3 isolated in Hebei Province
Since April 2022, H3N8 AIVs have led to several public health incidents of human infections in China, raising concerns about the potential risk of cross-species transmission of novel recombinant AIVs.14, 15,16 And we first identified a novel recombinant H3N3 subtype AIV with HA gene provided by H3N8 AIV in Hebei province (Fig. 1B). From real-time RT-PCR, we preliminarily confirmed that virus sample No. 14 was M-positive for influenza A viruses, which was identified to be an H3N3 subtype by NGS analysis and named A/environment/Hebei/XT28/2023(H3N3).
Its eight gene fragments were analyzed separately for genetic evolution, and we found that the HA gene of H3N3 was provided by the H3N8 virus and that the NA gene was provided by the H10N3 virus, while reassortment was completed through the provision of internal genes from the H9N2 (genotype G57) virus (Fig. 1B, 1C, Supplementary Figure 1).20These data indicated that the H3 subtype is constantly undergoing reassortment to produce new subtypes of influenza viruses. Meanwhile, we found that the novel recombinant H3N3 virus isolated in northern China was highly genetically similar to the H3N3 virus A/chicken/China/NT322/2023 (H3N3) isolated in eastern China (Fig. 1B). 33 This suggested that this recombinant H3N3 may be transmitted through certain vectors, possibly migratory birds.
(SNIP)
In summary, we isolated 10 different subtypes of AIVs including the major AIV subtypes reported in recent years from environmental samples and analyzed the genes of the isolated viruses, including a novel reassortant virus, H3N3, which was found for the first time in Hebei, China. Our findings emphasize the fact that AIVs are in the process of continuous evolution and that reassortment is continuously occurring among different subtypes. Surveillance of migratory birds and poultry will facilitate early detection of emerging novel animal influenza viruses and other zoonotic diseases for effective response.
Although we get very little in the way of real-time reporting on avian flu out of China, their scientists continue to publish excellent (albeit, often belated) reports in the scientific journals.
The overarching message from these reports is that avian influenza viruses continue to expand - both in range and variety - across China, and that some of these viruses pose legitimate public health risks.
While most will end up as evolutionary failures, we need to pay attention, because it only take one over-achiever to send us down the pandemic path again.
