Reassortment: Influenza's Superpower
#17,888
Although yesterday's surprise announcement (see China NHC Statement: A Fatal Case of H3N2 and H10N5 Mixed Infection Discovered in Zhejiang Province) has understandably raised a lot of eyebrows, researchers have been aware of of H10's zoonotic threat for decades.
In 1984, a rather large outbreak in Swedish mink farms was found to be due to the H10N4 avian virus. This summary from the Archives of Virology.
An avian influenza A virus killing a mammalian species — the minkFast forward 20 years, and in the spring of 2004, PAHO published the following account of human infections with H10N7 in Egypt.
Received: 26 August 1985 Accepted: 26 August 1985
Summary During October of 1984 an influenza epidemic occurred on mink farms in the coastal region of South Sweden. Six strains of an influenza A virus were isolated. All six isolates were of the H10 subtype in combination with N4. The H10 subtype in combination with various N subtypes was hitherto only known to occur in avian strains, the prototype being the A/chicken/Germany/N/49 (H10N7) virus.
Emerging and Reemerging Infectious Diseases, Region of the Americas
Vol. 2, No. 18—7 May 2004
Avian Influenza Virus A (H10N7) Circulating among Humans in EgyptThe National Influenza Center (NIC) in Egypt and the WHO Influenza Collaborating Centre in the UK reported the isolation of Avian Influenza A (H10N7) from two human specimens. They refer to two one-year-old infants, residents of Ismaillia, who recovered after presenting a fever and cough. The father of one of them is a poultry merchant who frequently traveled between Isamillia and Damietta. In the latter town, five cases of the same virus were isolated from wild ducks between 18 and 22 April 2004, from samples taken from a market of hunted migratory birds. Additional preliminary investigation tested negative in 75 human samples collected in Ismaillia and in 13 samples from migratory birds from the same market. No influenza outbreak has been reported among poultry in Egypt. At present, there are no public-health implications from this event.Source: Report to PAHO by WHO/CDS/CSR/RMD (Geneva: World Health Organization, Communicable Diseases, Communicable Disease Surveillance and Response, Risk Containment, Mapping and Drug Resistance)
In 2008 H10N5 was detected in Chinese pigs in China's Hubei Province (see Complete Genome Sequence of an H10N5 Avian Influenza Virus Isolated from Pigs in Central China), raising concerns that it was better adapting to mammalian hosts.
In 2012, in EID Journal: Human Infection With H10N7 Avian Influenza, we looked at a 2010 outbreak among workers at a chicken farm in New South Wales, Australia. Although 7 abattoir workers reported mild symptoms, only 2 tested positive for the H10 virus.
A more serious outbreak occurred over the winter of 2013-2014 in Jiangxi Province, China when three severe H10N8 human infections (2 fatal) were reported (see EID Journal Human Infection with Influenza Virus A(H10N8) from Live Poultry Markets, China, 2014)).
Although the number of reported H10 infected humans remained small - possibly due to a lack of surveillance and testing - in 2014's BMC: H10N8 Antibodies In Animal Workers – Guangdong Province, China, we saw evidence that some people may have been infected with the H10N8 virus in China before the first case was recognized.
Also in 2014, in SwAM: European Seal Deaths Continue From H10N7 Flu, we saw estimates of more than 3,000 seals killed by avian H10N7 in Northern Europe. In 2016, in PLoS One: Pathology Of A/H10N7 In Harbor Seals, we saw evidence that ferrets were susceptible to infection, raising concerns over its zoonotic potential.
In the spring of 2019, in JVI: Aerosol Transmission of Gull-Origin Iceland Subtype H10N7 Influenza A Virus in Ferrets, we looked at additional research that found a `. . . . gull-origin H10N7 virus can be transmitted between ferrets through the direct contact and aerosol routes, without prior adaptation.'
In June of 2021 (see CHINA NHC Reports 1st Human H10N3 Avian Flu Infection - Jiangsu Province) China's National Health Commission made a very brief announcement on the first known human infection with avian H10N3. In that case, notification occurred just over a month after the patient was admitted to the hospital (April 28th, 2021).In 2022, we saw a A Cryptic Report of A 2nd H10N3 Case from Hong Kong's CHP, which was further described in in 2023 in Second Identified Human Infection With the Avian Influenza Virus H10N3: A Case Report.
Additionally, we've looked at a number of studies on H10Nx viruses circulating in wild birds and poultry - and their zoonotic potential - including:
J.I.A.:Genetic and Biological Properties of H10Nx influenza viruses in China
All of which brings us to a correspondence, published yesterday in The Lancet Microbe, from Chinese researchers, on the zoonotic potential of H10N3 viruses in China.
They report at least 15 genotypes - all with internal genes derived from the H9N2 virus - multiple AA mammalian adaptations - and a high binding affinity to α2,6 receptor cells, which are abundant in the human upper respiratory system.
While the correspondence is brief, it is accompanied by a 36-page Supplementary PDF which contains the backup for their findings. Follow the link to read the report in its entirety. I'll have a brief postscript after the break.
Open Access Published:January 31, 2024
To prevent further human infection, an in-depth and systematic assessment of the pandemic risk of these viruses is essential. In this Correspondence, we report key findings from our investigation of the genomic and biological features of the H10N3 viruses isolated from humans and chickens.
An influenza A virus (A/Jiangsu/428/2021) was isolated from a 41-year-old man in China, representing the first recorded case of human infection with H10N3. 1 During surveillance of live poultry markets in China from 2020 to 2022, we isolated 16 H10N3 viruses (appendix p 26). Phylogenetic analysis indicated that the haemagglutinin and neuraminidase genes belonged to the Eurasian lineage and formed a monophyletic group, suggesting a substantial evolutionary history of the novel H10N3 viruses before their detection (appendix pp 5, 11–12).
The six internal genes originating from the H9N2 avian influenza A virus were grouped into multiple clusters and categorised into 15 genotypes (G0 to G14; appendix pp 5–6, 13–18, 33–34), suggesting that H10N3 viruses continue to evolve and undergo frequent reassortment. Such a persistent pattern of reassortment might enhance the fitness of avian influenza viruses in chickens and mammals, thereby posing a substantial threat to public health.
Although the next pandemic could emerge from anywhere in the world (2009's H1N1 pandemic began in Mexico), Southeast Asia has long been considered `the cradle of influenza’; an area of the world where both human and animal influenza viruses circulate more-or-less year round, and where there are ample opportunities for viruses to spillover (both to, and from, animals).We identified multiple amino acid residues related to adaptation in mammalian hosts in these novel H10N3 viruses (appendix pp 6–7, 27–32), and both human-derived and chicken-derived isolates showed high affinity for sialic acid-α-2,6-galactose receptors (appendix pp 7, 19). The human-derived H10N3 virus can replicate at high frequencies in various mouse organs, displaying high pathogenicity in mice, with a median lethal dose of 1·2 log10 of the 50% egg infective dose (appendix pp 7–8, 20–22).Notably, the human-derived isolate was not transmitted to guinea pigs via respiratory droplets (appendix pp 9, 23–24). However, the chicken-derived virus CK/0132/21 was highly pathogenic to mice, with a median lethal dose of 3·2 log10 of the 50% egg infective dose, and could be transmitted between guinea pigs via respiratory droplets (appendix pp 7–9, 20–24). These results indicated that some chicken-derived viruses might hold the potential to evolve into a pandemic threat in the human population, without the need for prior adaptation.
The emergence of the novel H10N3 virus highlights the persistent and evolving threat posed by the diverse array of avian influenza viruses found in China. Given the occurrence of asymptomatic infections caused by these novel H10N3 viruses in chickens (appendix pp 9–10, 25), controlling their widespread propagation in poultry is a challenging task, especially when considering previous experiences with avian H9N2 viruses.4,5Consequently, we strongly recommend immediate and meticulous surveillance, including regular or random sampling and testing, genomic monitoring in both animal and human populations, and heightened public awareness through widespread publicity, emphasising utmost urgency.
While China's government may be slow to release details on outbreaks or spillover events, China's scientific community has not been shy about issuing strong statements regarding the zoonotic potential of a wide variety of emerging pathogens (see here, here, here, here, and here in just the past few months).
Which suggests the next pandemic is not only inevitable, it may be closer than you think.
