Factsheet on A(H3N8)

Avian influenza A(H3N8) viruses are some of the most commonly detected subtypes in wild birds and have been found in live poultry markets in Asia, causing little to no sign of disease. Spill-over infections of A(H3N8) avian influenza viruses have been reported in mammals, including dogs, seals, and horses. Transmission to humans is sporadic, and the result of direct or indirect exposure to infected live or dead poultry or contaminated environments.  

To date, three people (one adult and two children) have been infected with avian influenza A(H3N8) globally, all from China. Two of them developed severe disease, with one of them dying, while one, a child, had mild disease. These cases occurred within less than a year of the first report of an A(H3N8) human case in April 2022 (the most recent case occurred in March 2023). All cases had exposure to live poultry prior to the development of symptoms, and no new cases were reported among their close contacts. 

No cases of low pathogenic avian influenza A(H3N8) have been detected in the EU/EEA in birds to date, and nor have any cases of A(H3N8) infections in humans. The risk of human infection in the EU/EEA is currently considered very low. However, people should not touch dead or sick birds due to the risk from other avian influenza subtypes circulating in the EU/EEA. Occupationally exposed groups are advised to use personal protective equipment when working with sick or dead birds or cleaning contaminated environments. 

Detailed description of human cases of A(H3N8) infection 

April 2022

The first human infection reported due to avian influenza A(H3N8) virus was on 26 April 2022: a four-year-old boy in Zhumadian City, Henan Province, China, developed respiratory symptoms on 5 April 2022 and was admitted to hospital and ICU with severe disease progression and pneumonia on 10 April 2022. He recovered. Exposure to backyard poultry and participating in the cooking and eating of chicken was reported before the onset of symptoms. 

First case in ECDC’s Communicable Disease Threats Report (CDTR).

May 2022

On 25 May 2022, China reported a second human case with avian influenza A(H3N8): a five-year-old boy from Changsha City, Kaifu District, Hunan Province, China, developed mild respiratory symptoms (fever and chills) on 9 May 2022 and tested positive. The boy visited a live bird market prior to onset of symptoms. This infection occurred approximately 620 kilometres from the location of the first case. 

The two cases in 2022 were described in Avian influenza overview, March–June 2022.

March 2023

The most recent case was reported on 28 March 2023, in a 56-year-old woman from Zhongshan City, Guangdong Province, China. She developed symptoms on 22 February 2023, was hospitalised for severe pneumonia on 3 March 2023, and subsequently died on 16 March 2023. The woman had multiple co-morbidities, exposure to backyard poultry, and a history of activities related to wild birds before the onset of symptoms. No additional cases among her contacts have been reported to date. There is no sequence information available about this case so far. Source: WHO 

Recent report in ECDC’s CDTR covering all three cases.

Figure 1. Human infections with avian influenza A(H3N8), 2022-2023 (updated on 12 May 2023) 

Animal and sequence data 

Genetic analysis of the avian A(H3N8) virus that caused the human infections revealed that the gene composition of the human A(H3N8) viruses was different from the previously reported animal A(H3N8) viruses. The human A(H3N8) virus possessed the Eurasian avian H3 gene, North American avian N8 gene, and internal genes of A(H9N2) Eurasian lineage viruses, which have donated their internal genes to multiple subtypes of influenza A viruses. All genes are of avian origin. Sequences of the two human isolates, A/Henan/4-10CNIC/2022 (first case) and A/Changsha/1000/2022 (second case), are novel triple-reassortant avian A(H3N8) viruses. 

Similar A(H3N8) viruses have been detected in chickens and wild birds in China. Some isolated viruses from birds have been shown to be able to replicate in human cell lines in vitro and can also bind to both avian and human receptors relevant for the virus to enter cells. No markers relevant for mammalian adaptation have been identified in viruses from birds. 

ECDC assessment 

These influenza A(H3N8) viruses have so far not been identified in European wild birds or poultry and therefore currently pose a very low risk for people in the EU/EEA. Nevertheless, it is crucial to monitor these viruses and investigate any new human cases. 

Literature 

• Sit THC, Sun W, Tse ACN, et al. Novel Zoonotic Avian Influenza Virus A(H3N8) Virus in Chicken, Hong Kong, China. Emerg Infect Dis 2022; 28(10). 
• Yang R, Sun H, Gao F, et al. Human infection of avian influenza A H3N8 virus and the viral origins: a descriptive study. Lancet Microbe 2022. 
• Wen F, Zhang X, Guo J, et al. Emergence of H3N8 avian influenza viruses possessing tri-basic hemagglutinin cleavage sites in China. J Infect 2022. 
• Wan Z, Jiang W, Gong J, et al. Emergence of Chicken Infection with Novel Reassortant H3N8 Avian Influenza Viruses Genetically Close to Human H3N8 Isolate, China. Emerg Microbes Infect 2022: 1-10. 
• Cheng D, Dong Y, Wen S, Shi C. A child with acute respiratory distress syndrome caused by avian influenza H3N8 virus. J Infect 2022; 85(2): 174-211. 
• Li P, Niu M, Li Y, et al. Human infection with H3N8 avian influenza virus: A novel H9N2-original reassortment virus. J Infect 2022. 
• Tan X, Yan X, Liu Y, et al. A case of human infection by H3N8 influenza virus. Emerg Microbes Infect 2022: 1-25. 
• Pu J, Wang S, Yin Y, et al. Evolution of the H9N2 influenza genotype that facilitated the genesis of the novel H7N9 virus. Proc Natl Acad Sci U S A 2015; 112(2): 548-53. 
• Wang J, Jin X, Hu J, et al. Genetic Evolution Characteristics of Genotype G57 Virus, A Dominant Genotype of H9N2 Avian Influenza Virus. Front Microbiol 2021; 12: 633835. 
• Cheung JTL, Tsang TK, Yen HL, et al. Determining Existing Human Population Immunity as Part of Assessing Influenza Pandemic Risk. Emerg Infect Dis 2022; 28(5): 977-85. 
• Bao P, Liu Y, Zhang X, Fan H, Zhao J, Mu M, et al. Human infection with a reassortment avian influenza A H3N8 virus: an epidemiological investigation study. Nat Commun. 2022 Nov 10;13(1):6817.