Friday, November 04, 2022

Emerging Microbes & Inf.: H9N2 Cluster Among Humans, Chickens & Pet Cat - China, 2018


Despite being an LPAI (low path avian influenza) virus, and producing relatively mild symptoms in humans, H9N2 is viewed by many as an important and influential player in the avian flu world.

So, while H9N2 may not be at the very top of our pandemic threats list, it is still regarded as having at least some pandemic potential (see CDC IRAT SCORE), and several candidate vaccines have been developed

All of which brings us to a fascinating report, published overnight in Emerging Microbes and Infections, that provides the details of an investigation of a cluster of H9N2 infections (human x 2, chickens, and a  pet cat) in Guangxi, China in October of 2018.  

A check of subsequent monthly WHO Influenza at the Human-Animal-Interface reports (here, here, here, here, and here) shows that China reported 6 H9N2 cases between Nov 1st 2018 and April  2019 - all among young children -  but these two cases do not appear.

In addition to the infection of the family cat (see A Dog & Cat Flu Review), this outbreak is unusual in that most H9N2 cases are one-off, and we rarely hear of clusters of infection.  Of note, the two human cases reported atypical (non-respiratory) symptoms of diarrhea, abdominal pain, and arthralgia.

We also learn from this report that the H9N2 clade 1.2, lineage Y280 virus detected had an exclusive binding preference for mammalian (a2,6) receptor cells, and could replicate and cause pathological changes in mice. 

This is a lengthy, and highly detailed report, and is well worth reading in its entirety.  I've only posted some excerpts, so follow the link to read:

Genetic, biological and epidemiological study on a cluster of H9N2 avian influenza virus infections among chickens, a pet cat, and humans at a backyard farm in Guangxi, China


During an investigation in October 2018, two people with diarrhoea, mild abdominal pain, and mild arthralgia symptoms in Guangxi, China, were identified as infected by H9N2 avian influenza virus (AIV). Four H9N2 AIVs were isolated from one of two patients, a pet cat, and a dead chicken (two respective isolates from its lung and kidney tissues) bred by the patients at a backyard farm.

Epidemiological investigation indicated that the newly bought chicken died first, and clinical syndromes appeared subsequently in the two owners and one cat. Furthermore, the two individuals possessed high H9N2-specific hemagglutination inhibition and microneutralization antibodies. Shared nucleotide sequence identity (99.9%–100%) for all genes was detected in the four H9N2 isolates, and hemagglutinin (HA) T138A located on the receptor binding domain (RBD), resulted from nucleotide polymorphisms that were exclusively found in the isolate from the female patient. 

Moreover, HA K137N on the RBD was found in isolates from these three host species. Importantly, these four H9N2 isolates presented an exclusive binding preference for the human-type receptor (α2-6-SA), and could replicate and cause pathological changes in mice. 

Phylogenetic analyses showed that these four isolates clustered together and belonged to clade 1.2, lineage Y280. In addition, H9N2 viruses of human origin are genetically divergent and interspersed with the widespread poultry-origin H9N2 AIVs. All these results indicate a high risk of H9N2 AIVs in public health, and effective prevention and control measures against H9N2 AIVs should be considered and performed for both animal and human health.



Based on similar clinical signs in two human cases and epidemiological, serological, and virological studies, a cluster of human cases, a sick pet cat, and chicken infections caused by H9N2 AIVs were identified at a backyard farm in Guangxi Province, China, in October 2018. Four H9N2 AIVs were isolated from a patient, cat, and chicken. Nucleotide sequence identity of over 99.9% for each gene segment of the four H9N2 isolates indicated that only one type of H9N2 AIV circulated in the farm and was later transmitted across species. 

At the beginning of this outbreak, the clinical symptoms first occurred in the majority of newly bought chickens rather than in the two originally raised chickens, suggesting that the H9N2 AIV was probably introduced into the farm by the imported chickens. Given the earliest clinical onset date reported in the chickens and later clinical syndromes displayed in the two persons and one cat, together with chickens were documented as the dominant host for H9N2 circulating in China, we inferred that the virus could be transmitted from infected chickens to cats and/or humans by directly or indirectly contact, which also conforms to the lack of evidence for H9N2 transmission between mammals [46]. 


In summary, the cluster of H9N2 infections among humans, chickens, and a cat has raised attention to interspecies transmission and disease ecology of H9N2 AIVs. The endemicity in poultry, wide spatial distribution, and multiple susceptible hosts increase the likelihood of human exposure to the virus.

Furthermore, a human-type receptor preference, genetically divergent viruses that infect humans, and few overt clinical symptoms highlight the risk of infection and adaption of H9N2 in humans. Targeted prevention and control should be urgently performed to eliminate H9N2 AIVs (especially the dominant clades) circulating in poultry farms and live poultry markets. Surveillance of human H9N2 infections, especially in workers occupationally exposed to poultry, should be enhanced to monitor the emergence of human-adapted H9N2 viruses and provide early warning of a potential outbreak or pandemic.

          (Continue . . . )

In 2018's Vet. Sci.: The Multifaceted Zoonotic Risk of H9N2 Avian Influenza, we looked at the growing risk from avian H9N2, including the rise of the Y280 lineage of the virus, which prompted the CDC to add it to their IRAT list in 2019, putting it in the Moderate Risk category. 

H9N2: Avian Influenza A(H9N2) Y280 lineage [A/Anhui-Lujiang/39/2018] Virus

Low pathogenic avian influenza A(H9N2) viruses are enzootic in poultry in many countries in Africa, Asia, the Middle East, and Europe. Since the late 1990s when the first human infections with avian influenza A(H9N2) virus were identified, detection of this virus has been reported infrequently in humans and in swine and other mammals. In 2018, there were 7 reported human infections, most with known exposure to poultry and with the majority involving viruses of the Y280 lineage.

Summary:  A risk assessment of avian influenza A(H9N2) Y280 lineage A/Anhui-Lujiang/39/2018 virus was conducted in July 2019. The overall IRAT risk assessment score for this virus falls into the moderate risk category. The summary average risk score for the virus to achieve sustained human-to-human transmission was 6.2. The average risk score for the virus to significantly impact public health if it were to achieve sustained human-to-human transmission was 5.9, also in the moderate range. For a full report click here pdf icon[356 KB, 5 pages].

While most reported H9N2 infections are mild or moderate, in November of 2021 China reported a rare fatal outcome in a 39-year-old man from Qiandongnan Autonomous Prefecture, Guizhou Prefecture. 

While H9N2 doesn't have the fearsome reputation of H5N6 or H7N9, it reassorts readily with other viruses and has shown an increasing ability to infect humans (and other mammals), making it very much worth our attention.