#17,867
Although many infections are undoubtedly missed - both in China, and around the world - 2021 saw the highest number of confirmed human avian H9N2 infections reported to date. In January 6th's CDTR, the ECDC reported:
As of 3 January 2024, and since 1998, a total of 130 laboratory-confirmed cases of human infection with avian influenza A(H9N2) viruses, including two deaths, have been reported in eight countries: China (117), Egypt (4), Bangladesh (3), Cambodia (2), Oman (1), Pakistan (1), India (1) and Senegal (1). Most of the cases were children with mild disease.
As an LPAI (low path avian influenza), H9N2 is not considered a `reportable' disease by WOAH (formerly the OIE), even though it is zoonotic. We've seen seroprevalence studies which suggest people with exposure to infected poultry often develop H9 antibodies, suggesting mild or asymptomatic infection.
While admittedly not at the very top of our list of pandemic concerns, the CDC has 2 different lineages (A(H9N2) G1 and A(H9N2) Y280) on their short list of influenza viruses with zoonotic potential (see CDC IRAT SCORE), and several candidate vaccines have been developed.
Control of H9N2 has proved difficult, despite more than 20 years of aggressive poultry vaccination in China (and elsewhere) against the virus. (see J. Virus Erad.: Ineffective Control Of LPAI H9N2 By Inactivated Poultry Vaccines - China).
Five years ago, in EID Journal: Two H9N2 Studies Of Note, we looked at two reports which suggest that H9N2 continues to evolve away from current (pre-pandemic and poultry) vaccines and is potentially on a path towards better adaptation to human hosts.
Whether as a standalone zoonotic threat, or a co-conspirator with another emerging virus (see EID Journal: Natural Reassortment of EA H1N1 and Avian H9N2 Influenza Viruses in Pigs, China), concern over H9N2's evolution continues to grow.
All of which leads us to a new study, published in Frontiers of Public Health, that looks at the > 2 dozen human H9N2 infections reported in China in 2021. Due to its length, I've only posted the Abstract and some excerpts.
Follow the link to read it in its entirety. I'll have a bit more after the break.
Reported human infections of H9N2 avian influenza virus in China in 2021
Min Tan1 Xiaoxu Zeng1 Yiran Xie1 Xiyan Li1 Jia Liu1 Jiaying Yang2 Lei Yang1 Dayan Wang1*1National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, Beijing, China
2School of Public Health (Shenzhen), Sun Yat-sen University, Guangdong, China
Introduction: The continued emergence of human infections of H9N2 avian influenza virus (AIV) poses a serious threat to public health. The prevalent Y280/G9 lineage of H9N2 AIV in Chinese poultry can directly bind to human receptors, increasing the risk of spillover infections to humans. Since 2013, the number of human cases of H9N2 avian influenza has been increasing continuously, and in 2021, China reported the highest number of human cases, at 25.
Methods: In this study, we analyzed the age, geographic, temporal, and sex distributions of humans with H9N2 avian influenza in 2021 using data from the National Influenza Center (Beijing, China). We also conducted evolutionary, gene homology, and molecular characterization analyses of the H9N2 AIVs infecting humans.
Results: Our findings show that children under the age of 12 accounted for 80% of human cases in 2021, and females were more frequently affected than males. More cases occurred in winter than in summer, and most cases were concentrated in southern China. Human-infecting H9N2 viruses showed a high level of genetic homology and belonged to the prevalent G57 genotype. Several additional α2,6-SA-binding sites and sites of mammalian adaptation were also identified in the genomes of human-infecting H9N2 viruses.
Discussion: Therefore, continuous monitoring of H9N2 AIV and the implementation of further measures to control the H9N2 virus in poultry are essential to reduce the interspecies transmission of the virus.
Introduction
Since the 1990s, the H9N2 avian influenza virus (AIV) has been detected in poultry and mammalian species, including chickens, ducks, smaller poultry, and pigs, in China (1–3). The virus has continuously evolved, resulting in multiple lineages, of which the G1, G9/Y280, and Y439 lineages continue to circulate in poultry (4, 5). The G9/Y280 lineage of H9N2 AIV has predominated in China in recent years. Since the emergence of the G57 genotype, which is better adapted to chickens, it has become predominant and has caused widespread outbreaks (1, 6).
Ongoing epidemics of H9N2 AIV in poultry increase the risk of spillover infections in humans. The first case of human H9N2 AIV infection was detected in Hong Kong SAR, China, in 1998. Since 2013, there have been increasing reports of human infections of H9N2 AIV (7). Several studies have shown that the majority of recent avian-origin H9N2 AIVs have a strong binding affinity for a human respiratory receptor (7, 8), and serological surveys have shown higher positivity among poultry-associated workers (9, 10). Therefore, assessing the pandemic risk of current H9N2 AIV genotypes is important and urgent.
In this study, we collected and analyzed data on human H9N2 AIV infections in China in 2021. We examined the epidemiological and genetic characteristics of the virus to extend our understanding of human infections and the risks they pose.
(SNIP)
Discussion
In this study, we analyzed the human H9N2 AIV infections reported in China in 2021, the year in which the highest number of H9N2 cases was recorded to date. We examined the epidemiological and genetic characteristics of the patients and isolates. H9N2 infections occurred most frequently in winter in Southern China and mainly occurred in children under 12 years old, who accounted for 80% of all cases. More female subjects were infected than male subjects. Therefore, the prevalence of H9N2 AIVs must be closely monitored to prevent cross-species transmission.
Host barriers largely restrict the cross-species transmission of AIVs. In recent years, the α2,6-SA-binding ability of H9N2 has increased continuously, and the predominant strains that have emerged show dual receptor binding or preferentially bind α2,6-SA (8, 39). HA Q226 L plays a critical role in receptor binding and was detected in all 16 viruses in this study. Moreover, increased α2,6-SA-binding sites, such as 155 T, 183 N, and 190 V, were also found in the H9N2 viruses that infected humans. Although most H9N2 viruses do not have well-known mammalian adaptation markers, such as PB2 627 K and 701 N, several amino acid residues that facilitate mammalian adaptation were detected, including PB2-588 V, PB1-368 V, PA-356R, and PA-409 N.
Throughout its evolution, the genetic diversity of H9N2 AIV has increased, with mutations that adapt the virus to mammalian hosts and may increase the risk of human infection. High levels of H9N2 AIV among birds, especially poultry, may also increase the opportunities for virus spillover and human infections. Serious efforts are required to constrain the virus in poultry. Continued monitoring of H9N2 AIV, including its close genetic surveillance and phenotypic characterization in animal models, should be incorporated into risk assessment strategies.
Conclusion
Since 2013, the number of human cases of H9N2 avian influenza has been steadily increasing, and in 2021, China reported the highest number of human cases, at 25. Children under the age of 12 accounted for 80% of human cases in 2021, and female subjects were more frequently affected than male subjects. More cases occurred in winter than in summer, and most cases were concentrated in Southern China. Human-infecting H9N2 viruses showed a high level of genetic homology and belonged to the prevalent G57 genotype. Continuous monitoring of H9N2 avian influenza viruses and further measures to control the H9N2 virus in poultry are essential to reduce the interspecies transmission of the virus.
For a ubiquitous, low pathogenic avian flu virus - one that rarely infects humans, and usually only produces mild illness - we spend an awful lot of time looking at, and trying to analyze, avian H9N2.
But it is not without good reason; over the years H9N2 has shared its internal genes with - and thereby helped to create - some of the most dangerous avian flu viruses (H5N1, H7N9, H3N8, H5N6, etc.) on the planet.
Some additional past blogs on this problematic virus include:
Mainland China Reports 2 Human LPAI H9N2 Infections (Sichuan Province)
Taiwan CDC: 1st Outbreak of Avian H9N2 In Poultry
Viruses: Genetic Evolution of Avian Influenza A (H9N2) Viruses in Uganda & Evidence of Mammalian Adaptation
HK CHP Reports 4 Human H9N2 Cases On The Mainland
PLoS Path: H9N2 Virus-derived M1 Protein Promotes H5N6 Virus Release in Mammalian Cells
ECDC: A Fatal H9N2 Case In China & Risk Assessment
