On March 27, 2023, the National Health Commission (NHC) of the People’s Republic of China notified the World Health Organization (WHO) of a confirmed case of human infection with avian influenza A (H3N8) virus. The patient was a 56-year-old woman from Guangdong Province, whose illness began on February 22, 2023. She was hospitalized for severe pneumonia on March 3 and died on March 16.
This is the third human infection with the H3N8 avian influenza virus described worldwide and the first confirmed death. Preliminary epidemiologic investigation of this event suggests that exposure to a live bird market may have been the cause of the infection.
Contact with poultry or wild birds as a trigger
The National Health Commission of China reported the first case of human infection with the H3N8 subtype of avian influenza virus on April 26, 2022. The patient was a 4-year-old boy living in Henan province, China, and that he had been exposed to poultry.
The boy developed a recurring fever, severe pneumonia, and liver and kidney failure, but survived. A month later, the Hunan Provincial Center for Disease Control and Prevention announced the second human case of H3N8 in a five-year-old boy from Changsha city who developed a mild illness.
So far, 11 avian influenza virus subtypes have been identified with the capacity to cause infection in humans, especially the H5N1, H5N6, H6N1, H7N7, H7N9, H9N2 and H10N8 subtypes. However, one of the most ubiquitous hemagglutinin (H) subtypes of avian influenza viruses is H3, which exhibits a wide host range.
In mammals it causes severe respiratory diseases.
Specifically, H3N8 avian influenza viruses circulate naturally in both wild birds and domestic chickens and ducks. But sporadic transmission events to multiple mammalian species, including dogs, pigs, horses, seals, donkeys, and recently humans, are of great concern. Especially since it can cause serious respiratory diseases and even death in them. This was the case in 2012, when H3N8 was blamed for the deaths of more than 160 seals off the northeast coast of the United States after causing fatal pneumonia.
On the other hand, experiments in vitro have shown that H3N8 has the potential to successfully infect pigs. This is an added concern, because pig cells have receptors for both human influenza viruses, specifically alpha 2-6 sialic acid, and avian influenza viruses, specifically alpha 2-3 sialic acid. . This situation favors that these animals can act as viral shakers, allowing the appearance of a potential H3N8 subtype that can effectively enter human cells.
In fact, it is possible that the appearance of some point mutation could facilitate the transmission of H3N8 to mammals.
In the first documented human infection with H3N8, the case of the Henan boy, a reassortant H3N8 virus was isolated, the strain A/Henan/ZMD-22-2/2022, which carried genes for hemagglutinin (H) and neuraminidase (N ) of avian origin, in addition to genes acquired from the Eurasian lineage H9N2 virus. Molecular substitution analysis revealed that hemagglutinin maintained binding specificity to the avian-type receptor, but that the RNA polymerase 2 (PB2) gene exhibited a sequence change, specifically the E627K mutation consisting of a glutamic substitution. by lysine at position 627. This change is associated with increased virulence and transmissibility in mammalian animal models. In addition, the N30D and T215A mutation in the M gene and the P42S mutation in the NS gene were also observed, which are associated with increased virulence in animal models.
In fact, nasopharyngeal and anal samples from the family’s dog and cat contained H3N8 genetic material with a sequence identical to the child’s virus. Dogs are particularly susceptible to influenza A viruses, including H3N2 and H3N8.
As if that were not enough, seroarchaeological evidence indicates that the 1889-1893 pandemic, known as the “Russian flu” and which killed more than a million people worldwide, could have been caused by an H3N8 virus.
Everything suggests, therefore, that the H3N8 influenza virus may cross species barriers and pose a threat to human health.
It is not transmitted between humans and cases are sporadic.
Fortunately, available epidemiological and virological information suggests that H3N8 avian influenza viruses do not have the capacity for sustained human-to-human transmission. Therefore, the current assessment is that the probability of person-to-person spread is low.
Given the current global situation, and the continuous contact that many people may have with sick birds, it is expected that more sporadic cases of H3N8 infection in humans will appear in the future. Further research in both humans and animals is needed to better understand the immediate risk posed by the H3N8 subtype to public health. For this reason, for the moment, it continues to be vital to carry out serious and exhaustive global surveillance, which makes it possible to detect virological, epidemiological, and clinical changes associated with circulating influenza viruses.
In the meantime, to minimize the risk of infection, we must make the population aware of the importance of maintaining good hand hygiene, as well as avoiding contact with animals that are sick or dead from unknown causes. You should also avoid contact with high-risk environments, such as live animal markets and farms, live poultry, or surfaces that may be contaminated with birds or bird feces.
