#18,806
Yesterday, in HK CHP Reports 2 Mainland H9N2 Cases we looked at the sparse details provided on the 17th & 18th human H9N2 infections reported by China in the first half of 2025.While these numbers are thought to be significant undercounts, this comes on the heels of last year's record 22 cases. Prior to 2015, relatively few human cases were reported (see FluTracker's H9N2 list).
Sporadic cases have been reported in other countries (India, Bangladesh, Vietnam, Cambodia, Egypt, etc.), but 95% of the world's reported H9N2 infections come from China.
Global surveillance has always been limited, making it difficult to draw firm conclusions on the increased numbers being reported.
Most infections have been mild, and the vast majority have been reported in young (mostly female) children, but over the past few years we've seen an increasing number of older patients reported; including some severe cases.
LPAI H9N2 is consider a Low Path (LPAI) virus (in poultry), and is therefore not a `reportable' disease to WOAH. H9N2 can cause significant morbidity and mortality in poultry, and so - while not mandatory - poultry vaccination against H9N2 in China - which began in the late 1990s - is nearly universal.
But, as we've discussed often - while existing H9 vaccines can greatly reduce poultry morbidity and mortality - they don't prevent the spread and continue evolution of the virus (see J. Virus Erad.: Ineffective Control Of LPAI H9N2 By Inactivated Poultry Vaccines - China).
Last April we looked at another cautionary report in NPJ Vaccines: Impact of Inactivated Vaccine on Transmission and Evolution of H9N2 Avian Influenza Virus in Chickens, which concludes that inactivated vaccines have failed to prevent - or even reduce - H9N2 in China's poultry, and may have driven viral evolution (including mammalian adaptations).
Simply put - H9 vaccines have greatly reduced losses in poultry - but they have been ineffective in stopping (usually silent) transmission of the virus, and its continued evolution.
This is not only bad for the future evolution and spread of this subtype, H9N2 is particularly promiscuous, and easily reassorts with a wide variety of subtypes; often producing more dangerous H3, H5, H7, and H10 genotypes.
While its generally mild presentation in humans may reduce its threat, the CDC has identified 2 different lineages (A(H9N2) G1 and A(H9N2) Y280) as having some pandemic potential (see CDC IRAT SCORE) - and several candidate vaccines have been developed.
But much of H9's evolution remains hidden.
Six weeks ago, in Nature: Genetic diversity of H9N2 avian influenza viruses in poultry across China and implications for zoonotic transmission, we looked at yet another cautionary report from Chinese researchers warning on the growing public health threat posed by and increasingly divergent array of H9N2 viruses.
All of which brings us to a new report, published last week in Poultry Science which characterizes 61 H9N2 (AIVs) isolated from chickens and waterfowl in Southern China between 2018 and the spring of 2024, which finds that the vast majority of them now bind preferentially to human-type (α2,6-linked) receptor cells.
This shift in H9N2 - from preferentially binding to avian α2,3-linked receptor cells to human receptors - is a trend we've been following for years.
The authors report that several key amino acid mutations (Q226L, I155T, H183N) for human receptor binding were detected in the subset of isolates that were fully sequenced.
They could, however, still infect and replicate efficiently in vaccinated poultry.
Due to its length, and technical nature, I've only posted the abstract and some excerpts. Those desiring a deeper dive will want to follow the link to read it in its entirety.
I'll have a brief postscript after the break.
Characterization of H9N2 avian influenza virus isolated from chickens and waterfowl in parts of Southern China from 2018 to April 2024
Wanting Zhou 1 2 #, Jun He 3 #, Fangfang Qiao 1 2, Mengyao Wang 1 2, Qinghang Zeng 1, Yang Liu 4, Yue Zhao 3, Liji Zhang 2 5, Ting Li 2 6, Shouwen Du 2, Minhua Sun 2, Ming Liao 1 2 6
16 July 2025
https://doi.org/10.1016/j.psj.2025.10558
Abstract
The H9N2 subtype of avian influenza virus (AIV) has become endemic in poultry farms across China, providing internal genes for other subtypes of viruses and occasionally having the ability to infect humans, thereby posing a significant public health threat. In this study, 61 H9N2 viruses were isolated from chickens and waterfowl in Southern China between 2018 and April 2024.We characterized their genetic derivation, antigenic diversity, receptor-binding specificity, neuraminidase (NA) activity, replication, and transmission in chickens and systematic pathological analysis.
Genetic analysis revealed that 60 isolates belonged to the h9.4.2.5 lineage, while 7, 20, and 33 H9 strains belonged to the h9.4.2.5a, b, and c branches, respectively. One isolate belonged to the h9.4.2.1 lineage. Mainly tested H9N2 strains preferentially bound to human-type receptors, except one virus exhibiting dual receptor-binding specificity.Antigenicity analysis indicated that these tested viruses could be classified into 2 separate antigenic clusters. In addition, the selected viruses efficiently replicated and transmitted in chickens at a high dose induction. Continuous and systematic surveillance of H9N2 virus mutation and infection in poultry farms is crucial for early detection of novel recombinant viruses with pandemic potential and for enhancing biosecurity control.(SNIP)
DISCUSSIONH9N2 AIVs, which typically provide the internal genes to generate new recombinant strains, have been circulating in birds around the world for several years and have the potential to cause new widespread outbreaks. Since 2014, H9N2, becoming the dominant AIV subtype, has relentlessly mutated and become highly complicated as the most prevalent strain in China (Murakami et al., 2022).Notably, the comprehensive host spectrum is a non-negligible factor in infection and transmission of H9N2 AIVs, which may cause mammals, especially the potential for a human pandemic. However, H9 vaccines have been used for several years; this virus is still circulating in China. It is still urgent to continuously monitor the evolution of H9N2 AIVs to assess the mutation of viruses to prevent epidemics.
(SNIP)
However, the current vaccine strain belongs to 9.4.2.5a; the antigenic analysis here shows the uneven cross-reactivity of the chicken serum of selected H9N2 viruses and indicates that the current circulating viruses have undergone unpredictable antigenic drift. The vaccine could not wholly protect animals from infection with the H9N2 virus.
(SNIP)
In conclusion, a comprehensive analysis of the isolates from 2018-April 2024 in part of Southern China through comparative genetic evolution, receptor-binding specificity, chicken replication, transmission, and pathological injury. Our results emphasize that active surveillance of domestic birds will contribute to the early detection of the emergence and evolution of Virus mutation, cross-species transmission, and potential threats to human health.
While poultry and (potentially) livestock vaccination are being heavily touted to control H5N1, the experience with H9N2 reminds us that a poultry vaccination campaign alone isn't enough to solve the problem.
Vaccines must not only be properly and comprehensively applied, they must be a good match for the flu viruses currently in circulation. But as we've seen, vaccines are often inconsistently applied or used long after they've lost effectiveness.
- In 2012's Egypt: A Paltry Poultry Vaccine, researchers examined the effectiveness of six commercially available H5 poultry vaccines used in Egypt and found only one actually appeared to offer protection.
- Six years later, another study (see Sci. Reports: Efficacy Of AI Vaccines Against The H5N8 Virus in Egypt) found `. . . most of the commercial poultry H5 vaccines used in the present study were ineffective. . . '
- More recently, in 2023's WUR: 2 of 4 H5 Poultry Vaccines Tested Appear Effective Against H5N1, found ineffective vaccines were still being marketed.
But it requires the proper administration of proven, and continually updated vaccines, along with regular surveillance & testing of vaccinated flocks, and (if necessary) the quarantining or culling of infected birds.
Anything less, and we risk doing more harm than good.
