Tuesday, June 04, 2024

J. of Infect: The H5 Subtype of Avian Influenza Virus Jumped Across Species to Humans - a View from China

H5N1 Now Detected in 80 Herds across 9 States

#18,100

While it may be a case of whistling past a graveyard - judging by their silence - many countries appear to have adopted the notion that the mutation in the HPAI H5N1 virus in the United States (genotype B3.13) that has allowed it to spill over into cattle, is unique, and unlikely to be duplicated elsewhere in the world. 

Last week, the UK HAIRS Risk Statement On Avian Influenza (H5N1) In Livestock estimated that H5N1 genotype B3.13 presents ` at most, a very low risk' to the UK, citing a low likelihood of the virus being carried across the Atlantic to Europe. 

As a result, they report "There is currently no surveillance in dairy workers for AI A(H5N1)" and even that  " . . . it is unlikely that cases of conjunctivitis would be tested for AI A(H5N1)."

While is seems reasonable that the B3.13 genotype is unlikely to spread to the UK from the United States - it certainly seems possible that another genotype/mutation could emerge somewhere else in the world with a similar ability to infect livestock.

Which is precisely the concern expressed in a letter published over the weekend in the Journal of Infection, by Chinese scientists. 

The H5 subtype of avian influenza virus jumped across species to humans - a view from China

Juncheng Cai 1Lijin Lai 1,Rui LiQiuyan LinLibin ChenTao Ren
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Open Access Published:June 01, 2024 DOI:https://doi.org/10.1016/j.jinf.2024.106193

Dear Editor,

Recently, an article in your journal reported the risks of the infections of humans and other mammals with H5 subtype highly pathogenic avian influenza viruses (AIVs) in 2020–2023.1 In April, the World Health Organization (WHO) reported a case of human infection with highly pathogenic H5N1 AIVs, the first case of human transmission of H5N1 AIVs from a mammal in the United States, and the second case of human H5N1 AIVs infection in the United States.2The confirmed case is a farm worker at a Texas dairy farm who had a history of exposure to dairy cattle suspected of being infected with H5N1 AIVs. The infected person had no symptoms other than conjunctivitis and was advised to be isolated and receive antiviral drugs.2,3 

This is the first global case of highly pathogenic H5N1 AIVs infection in cattle and further infection of human. Furthermore, on May 22, the Centers for Disease Control and Prevention (CDC) of the United States announced a second case of human infection associated with the spread of H5N1 AIVs in dairy cattle. Human-to-human transmission of H5N1 AIVs has not been detected. By the end of April, several states in the United States reported H5N1 AIVs infections in dairy herds.

2 This suggests that cattle-to-cattle transmission of H5N1 AIVs may have occurred. Additionally, fatal systemic influenza infections have been reported in domestic cats fed with milk from infected cows. 4 This indicates that the virus can spread across species, posing a challenge to public health security in the United States.The earliest known H5N1 AIVs infection in humans dates back to the outbreak of the highly virulent H5N1 avian influenza in a live poultry market in Hong Kong in 1997.

5 This virus has spread globally since 2003. In recent years, highly pathogenic avian influenza caused by the H5N1, H5N2, H5N4, H5N5, and H5N6 subtypes of AIVs has become widespread in Europe, the Americas, Asia, and Africa, causing serious harm. Among them, H5N1 subtype AIVs are the most common, followed by the H5N8 subtype, and 2.3.4.4b is the dominant genotype of the circulating strain.  

6 Genetic analysis of the H5N1 patient confirmed that the infected virus belonged to the 2.3.4.4b branch.2 In recent years, most of the major circulating AIV strains in China have belonged to branch 2.3.4.4b.

7 We downloaded and screened the HA sequences (206 in total) of H5 subtype AIVs strains isolated from China over the past 3 years (January 1, 21 to now) from the GISAID EpiFlu database. The H5 subtype influenza strain sequences isolated from American dairy cattle since January 24 (Idaho, New Mexico, Texas, South Dakota, Michigan, Ohio, and Kansas, a total of seven states, each of which involved randomly selecting five sequences as representatives) were collected for comparison and construction of a phylogenetic tree, with one of the sequences 2.3.4.4 h as the main root for tree plotting. 

The H5N1 AIV strains recently isolated from infected cattle in the United States (blue marks) and some H5N1 strains isolated from China in the last 3 years (green marks) are relatively close in genetic distance according to the phylogenetic tree (Fig. 1).

This suggests that H5N1 AIVs circulating in the United States and China share a common origin, indicating that H5N1 AIVs in China are at risk of evolving into novel strains that infect mammals or even humans, potentially threatening public health security in China. Three strains of the H5 subtype AIVs isolated in China belong to the 2.3.4.4 h evolutionary branch. Although the genetic evolution is far from that of H5N1 AIVs strains in the United States, this threat remains a concern.

Since 2020, there has been an unexpected surge in the prevalence of H5 subtype AIVs. The prevalence of novel H5N1, H5N6, and H5N8 AIVs poses serious threats to the global poultry industry, ecosystems, and public health.7 From January 2020 to July 2023, a total of 310 cases of highly pathogenic H5 subtype AIVs in mammals have been reported in 17 countries, affecting companion animals such as domestic dogs and cats, land mammals such as red foxes and wolves, and marine mammals such as sea lions and seals, causing great concern worldwide.8
This indicates that the global avian influenza epidemic is more severe, and prevention and control face great challenges. In the current global H5 subtype AIVs epidemic, both surface genes of H5N1 AIVs showed a relatively high rate of evolution, indicating that H5N1 AIVs may have stronger evolutionary potential, which also means that there is a higher risk of H5N1 AIVs emerging in the future. Additionally, H5N1 AIVs show varying degrees of adaptive change in alpha-2,6-linked sialic acid receptor-associated sites, indicating that H5N1 AIVs are more likely to infect mammals.7
To cope with the new challenges brought by the epidemic of H5 subtype AIVs to public health security in China and the world, we must strengthen the surveillance of H5 subtype AIVs antigen mutations to detect and intervene in the early stage of new and re-emerging H5 subtype AIVs with public health risks. China's avian influenza vaccination is a successful case of prevention and control AIVs, and the development of new vaccine strains can reduce the potential consequences of antigenic mutations and curb the further spread of AIVs.
          (Continue . . . )


While H5N1 could still fizzle as a pandemic threat, given everything we've seen over the past 3 years (including scores of new genotypes, conquering both North and South America, spreading widely in marine mammals,  infecting goats, alpacas and cattle, and producing increasingly neurotropic infections in mammals), you'd think we'd be a bit more proactive. 

But in far too many places, `Don't test, don't tell' remains the preferred response. 

And unless and until that mindset changes, we can expect to continue to be surprised by H5N1 on a regular basis.