#18,930
While we are understandably focused on the continued evolution and spread of HPAI H5N1 around the globe, in China - over the past 24 months - we've seen roughly 50 human infections with LPAI H9N2 reported, mostly in children.
Given the relatively mild presentation of H9N2 in humans - and the infrequency of testing outside of big city hospitals - the actual number of cases in China is assumed to be much higher.LPAI H9N2 is a Low Path (LPAI) virus (in poultry), and is therefore not a `reportable' disease to WOAH. It can, however, cause significant morbidity and mortality in poultry, and so poultry vaccination against H9N2 in China - which began in the late 1990s - is nearly universal.
But, as we've discussed previously - 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).
Over the past couple of years we've seen increasing reports that some isolates now preferentially bind to human-type (α2,6-linked) receptor cells (see Characterization of H9N2 Avian Influenza Virus Isolated from Chickens and Waterfowl in Parts of Southern China from 2018 to April 2024).
The information we get out of China on human infections is generally cryptic - and follow ups are rare - but today we have an unusually detailed report (published this week in China's CDC Weekly), on 3 pediatric cases which were reported last April from Changsha City, Hunan Province, China.
The gist of the report (which we'll get to) is found in the discussion section:
Three children infected with H9N2 AIV were identified in Changsha in April 2025, and no epidemiological links were found between these mild and sporadic cases. Genetic analysis showed that the H9N2 viruses had enhanced binding ability to upper respiratory tract receptors, particularly the α2,6-sialic acid receptors.
The report goes on describe some of the notable HA mutations suggesting enhanced mammalian adaptation:
Analysis of receptor-binding sites showed that the HA proteins had mutations at amino acid positions H191N, A198V, Q226L, and Q234L, which potentially enhanced the binding ability of the virus to the receptor (5-6).
While there is still no evidence of sustained or efficient human-to-human transmission of H9N2, the virus continues on a path towards greater mammalian adaptation.
A few excerpts from the full report (but you'll want to read it in its entirety), after which I'll return with a postscript.
Chaoyang Huang1,2,&; Yi Liu1,&; Zheng Huang3; Shuilian Chen3; Zhifei Zhan1,2; Qianlai Sun1; Ruchun Liu3; Liang Cai1,2, , ;Kaiwei Luo1
Summary
What is already known about this topic?
A total of 117 H9N2 cases of human infection of Chinese origin had been reported to the World Health Organization (WHO) by May 9, 2025, with 22 of them originating in Hunan Province.What is added by this report?
This article reported on the investigation of three new H9N2 avian influenza virus (AIV) infections detected in Changsha, Hunan Province, in April 2025. No epidemiological link was found among them. Exposure to live poultry was identified as the primary risk factor for infection. Sequence analysis of the three H9N2 AIVs showed a similarity of 99.71%–99.82% between hemagglutinin (HA), and the homology of the neuraminidase (NA) genes was 98.41%–99.83%. Although the tests showed that the HA had enhanced binding ability to upper respiratory tract cells’ receptors, no evidence of sustained human-to-human transmission has been found so far.What are the implications for public health practice?
This study indicated that H9N2 AIV remains a public health issue in China. We need to strengthen publicity and education efforts to inform people of the potential risk of avian influenza virus, especially to keep children away from poultry and poultry-related facilities, to effectively prevent the occurrence of avian influenza A(H9N2) infection.
ABSTRACT
Introduction: In April 2025, three suspected human cases of avian influenza were identified in Changsha, China. Laboratory testing confirmed three cases of H9N2 AIV infection. This report summarizes the epidemiological findings from cases and contact investigations, along with genetic characterization of the isolated H9N2 strains.
Methods: Comprehensive epidemiological assessments were conducted for each confirmed case. Virus isolation and culture were performed using throat swab specimens obtained from the cases. Isolated H9N2 strains were sequenced using next-generation sequencing (NGS). HA and NA gene sequences were analyzed for homology; evolutionary trees were constructed; and key antigenic sites were examined to identify genetic features.
Results: All three cases were sporadic. No influenza-like illness was observed among close contacts or live poultry store employees during the 10-day medical monitoring period. Phylogenetic analysis indicated that the HA gene of all three H9N2 strains belonged to the A/Duck/Hong Kong/Y280/97 (Y280-like) clade within the Eurasian lineage. HA gene sequence homology was 99.7%–99.8%, and NA gene homology was 98.4%–99.8%. The HA protein cleavage site was identified as PSRSSR↓GLF. Several HA protein site mutations were detected — H191N, A198T/V, Q226L, and Q234L — that had been previously associated with increased binding to receptors. HA-232H, 234L, and 236G support a binding preference for the human-type sialic acid-α-2,6-galactose receptors.
Conclusion: All three H9N2 avian influenza cases were mild and involved reported exposure to poultry or related environments. Genetic analysis revealed high homology of HA and NA among the isolated viruses. No epidemiological links were identified between cases, and no evidence was found of sustained human-to-human transmission. Continued avian influenza surveillance and public health education are warranted.
The H9N2 avian influenza virus (AIV) is the most prevalent avian influenza virus circulating among poultry in China (1). While it primarily leads to economic losses in the poultry industry, it has also repeatedly crossed the species barrier to infect humans, raising public health concerns. Since 2015, China has consistently reported human H9N2 infections to the WHO, with 117 cumulative cases by May 9, 2025 (2). Among these, 19 cases were reported in Hunan Province by the end of 2024 (3), followed by three additional cases in April 2025.
Therefore, it is crucial to closely monitor variations in H9N2 infectivity — particularly its potential for cross-species transmission to humans. This study presents the epidemiological profiles of three human H9N2 cases detected through influenza-like illness (ILI) surveillance from Changsha, China, along with the molecular characteristics of the corresponding H9N2 viruses.
As we've discussed previously, Live Poultry Markets (LPMs) are an important venue for spillovers to humans, and testing of local markets where these children were exposed showed high levels of H9N2 virus in poultry.
The Changsha CDC conducted emergency monitoring of the sources of chickens and ducks in the live poultry stores of Case 1 and Case 2, as well as the Shuiduhe Market and Huangxing Town Market, on April 27, 2025.A total of 62 environmental samples were collected, and the nucleic acid test results showed that 33 samples were positive for H9N2 AIV, and 2 samples were positive for H5 AIV.
While H9N2 currently presents as a relatively mild virus in humans, it is also extremely promiscuous; willing and able to reassort with a wide variety of other influenza A viruses.
H9N2 is such a versatile virus, it has even been detected in Egyptian Fruit bats (see Preprint: The Bat-borne Influenza A Virus H9N2 Exhibits a Set of Unexpected Pre-pandemic Features).In nearly every novel avian flu virus of concern, you'll find internal gene contributions from H9N2 (see last January's Transboundary & Emerging Dis.: The H5N6 Virus Containing Internal Genes From H9N2 Exhibits Enhanced Pathogenicity and Transmissibility).
All of which suggests that, unless and until H9N2 can be better controlled, our avian flu woes may extend far beyond just H5Nx in the years ahead.
