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We've been following the H3N8 human infection reported out of Guangdong Province for more than 2 weeks, and over the past 24 hours we've seen a brief update from WHO WPRO and a statement from the CDC.
In the spring of 2022 China reported the first two known human infections with H3N8 - affecting two small children (one severely) - living roughly 400 miles apart.
Since H3N8 doesn't tend to seriously impact poultry, and until recently had never been known to infect humans, it has received relatively little attention. However:
- H3N8 remains a plausible cause of a global influenza pandemic that spread out of Russia in 1889-1900 (some researchers now suspect a coronavirus instead).
- about 60 years ago H3N8 jumped unexpectedly to horses, supplanting the old equine H7N7 and is now the only equine-specific influenza circulating the globe
- in 2004 the equine H3N8 virus mutated enough to jump to canines, and began to spread among greyhounds in Florida (see EID Journal article Influenza A Virus (H3N8) in Dogs with Respiratory Disease, Florida).
- in 2011 avian H3N8 was found in marine mammals (harbor seals), and 2012’s mBio: A Mammalian Adapted H3N8 In Seals, provided evidence that this virus had recently adapted to bind to alpha 2,6 receptor cells, the type found in the human upper respiratory tract.
- And lastly, in 2015's J.Virol.: Experimental Infectivity Of H3N8 In Swine, we saw a study that found that avian (but not canine or equine) H3N8 could easily infect pigs.
Today the WHO has published their first detailed DON update and risk assessment on this latest case from China, where they state that while additional sporadic spillover infections are likely, the likelihood of human-to-human spread is low.
First some excerpts from the WHO statement, after which I'll return with a brief postscript.
Avian Influenza A(H3N8) - China
11 April 2023
Situation at a glance
On 27 March 2023, the National Health Commission of the People’s Republic of China notified WHO of one confirmed case of human infection with an avian influenza A(H3N8) virus. This is the third reported case of human infection with an avian influenza A(H3N8) virus; all three cases have been reported from China.
Epidemiological investigation and close contact tracing have been carried out. There have been no other cases found among close contacts of the infected individual.
Based on available information, it appears that this virus does not have the ability to spread easily from person to person, and therefore the risk of it spreading among humans at the national, regional, and international levels is considered to be low. However, due to the constantly evolving nature of influenza viruses, WHO stresses the importance of global surveillance to detect virological, epidemiological and clinical changes associated with circulating influenza viruses which may affect human (or animal) health.
Description of the situation
On 27 March 2023, the National Health Commission of the People’s Republic of China notified WHO of one confirmed case of human infection with an avian influenza A(H3N8) virus. The patient was a 56-year-old female from Guangdong province with an onset of illness on 22 February 2023. She was hospitalized for severe pneumonia on 3 March 2023 and subsequently died on 16 March 2023.
The case was detected through the severe acute respiratory infection (SARI) surveillance system. The patient had multiple underlying conditions. She had a history of exposure to live poultry before the onset of the disease, and a history of wild bird presence around her home. No close contacts of the case developed an infection or symptoms of illness at the time of reporting.
Environmental samples were collected from the patient's residence and the wet market where the patient spent time before the onset of illness. The results of testing showed that the samples collected from the wet market were positive for influenza A(H3).
Epidemiology of the disease
Zoonotic influenza infections in humans may be asymptomatic or may cause disease. Depending on factors related to the specific virus and the infected host, disease can range from conjunctivitis or mild flu-like symptoms to severe acute respiratory disease or even death. Gastrointestinal or neurological symptoms have been reported but these are rare.
Human cases of infection with avian influenza viruses are usually the result of direct or indirect exposure to infected live or dead poultry or contaminated environments.
Public health response
The Chinese government has taken the following monitoring, prevention, and control measures:
- Enhanced monitoring and disinfection in the surrounding environment of the patient’s residence and suspected exposure areas;
- Public risk communication activities to improve public awareness and adoption of self-protection measures.
WHO risk assessment
Avian influenza A(H3N8) viruses are commonly detected globally in animals. Influenza A(H3N8) viruses are some of the most commonly found subtypes in birds, causing little to no sign of disease in either domestic poultry or wild birds. Cross-species transmission of A(H3N8) avian influenza viruses has been reported for various mammal species, including being endemic in dogs and horses.
This is the third reported human infection with A(H3N8) from China. Two previous cases were reported in April and May 2022. One of the previous cases developed a critical illness, while the other had a mild illness. Both cases likely acquired infection from direct or indirect exposure to infected poultry. So far, no additional cases linked with this case, nor the previous cases, have been reported. According to reports from health officials, the preliminary epidemiological investigation into this event suggests that exposure to a live poultry market may have been the cause of infection. However, it is still unclear what the exact source of this infection is and how this virus is related to other avian influenza A(H3N8) viruses that are circulating in animals. To better understand the current risk to public health, more information is needed from both human and animal investigation.
The transmission of avian influenza viruses from birds to humans is usually sporadic and happens in a specific context: most human infections with avian influenza viruses that have been reported previously were due to exposure to infected poultry or contaminated environments. Since avian influenza viruses continue to be detected in poultry populations, further sporadic human cases are expected in the future.
The available epidemiological and virological information suggests that avian influenza A(H3N8) viruses do not have the capacity for sustained transmission among humans. Therefore, the current assessment is that the likelihood of human-to-human spread is low. However, due to the constantly evolving nature of influenza viruses, WHO continues to stress the importance of global surveillance to detect virologic, epidemiologic and clinical changes associated with circulating influenza viruses which may affect human (or animal) health.
Three cases in a year does not make a pandemic threat, but it is unusual enough for us to take notice. It is also likely that some cases have gone undiagnosed, as a person would need to be sick enough to be hospitalized, and then lucky enough to have the right tests performed, for the virus to be identified.
With Mainland China the epicenter of cases, we are admittedly reliant upon the quality of surveillance and reporting by Chinese officials, a process that often hasn't been as speedy or transparent as we'd like.
Last September - following the first two announced cases - we looked at an analysis of the potential public health threat posed by avian H3N8 which was published in the International Journal of Infectious Diseases (see IJID: A Review Of The Pandemic Potential Of Avian H3N8) which cautioned.
Will the influenza A(H3N8) cause a major public health threat?
Hadi M. Yassine, Maria K. Smatti
Open Access Published:September 05, 2022
(Excerpt)
In summary, the ability of the H3 influenza subtype to infect humans is documented. This subtype has been shown to infect different mammalian species, including pigs. The ability of avian H3N8 to infect pigs raises significant concern about its ability to infect humans. Urgent studies are needed to understand the phenotypic characteristics of the recent H3N8 in humans, including receptor specificity, as well as the replication in human airway cells. It is unlikely that immunity against H3N2 will protect from H3N8, considering the significant antigenic changes. Cross-reactivity studies of the different H3N8 lineages are needed in this regard. Currently, an inactivated vaccine against H3N8 is available for use in horses. Whether this vaccine produces immunity against avian H3N8 remains to be studied. The availability of such resources might speed up the production of human vaccines if needed.
Avian H3N8 may have some advantage over avian H5 or H7 viruses, in that all known human influenza A pandemics (going back 130 years) have been either H1, H2, or H3 (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?).
But until it proves itself capable of transmitting efficiently from human-to-human, it is just one of nearly 2 dozen zoonotic influenza A viruses we continue to monitor with interest.
Any of which, frankly, has the potential to evolve into a pandemic strain with very little warning.
Say tuned.