“If H5 is ever going to become a pandemic, it will be now.” This is how Seema Lakdawala, influenza researcher at Emory University, in Atlanta (United States), summarizes the situation in the columns of Science, December 5, 2024.
The possibility of human-to-human transmission of avian influenza – infection of birds by an Influenza A virus – seems to have never been so close. The first human cases of avian flu were identified in 1997 in Hong Kong. It was subtype H5. As a reminder, the H5, H7 and H9 subtypes are the most likely to cause severe pathologies in birds with very high mortality, particularly in domestic poultry farms (chickens, turkeys, ducks).
Since 2021, a new variant of the H5N1 subtype, subclade 2.3.4.4b, has been circulating intensively globally. From migratory birds, the epizootic has spread to farmed poultry. And contaminations have been regularly detected in nearly thirty species of wild and domestic, terrestrial and marine mammals. Minks in Spain, seals and dairy cows in the United States, or even sea lions in Chile and Peru. Human cases have also been detected since 2021, in England, China, the United States, Ecuador, Laos, Nigeria, Russia, Vietnam, mainly of the H5N1 and H5N6 subtypes. In 2024, 53 human cases were recorded in the United States, without any human-to-human transmission being identified. However, the H5N1 virus now rises to an excellent position in the list of agents that threaten humanity with a new pandemic.
Few mutations needed for human-to-human transmission to be possible
For human-to-human transmission, scientists have since established the list of mutations that the H5N1 virus needed to spread widely among humans. And it’s short. It would need mutations in its polymerase, the enzyme the virus uses to copy its genome, that would allow it to replicate more easily. There would also need to be a change in its hemagglutinin (the H in H5N1), the protein that the virus uses to attach to cells. Objective: To stabilize for airborne transmission and the ability to bind to human upper respiratory cells.
These changes are indeed underway. According to Science, A study of blood samples from people working on H5N1-infected dairy farms in Michigan and Colorado found that many human infections go unnoticed. But each of them is an opportunity for the virus to adapt a little more to humans. And still according to a pre-publication of an article in Science, the clade 2.3.4.4b virus currently in circulation binds better to human epithelial cells of the respiratory tract than previous versions of the H5N1 virus.
In addition, according to another article published on December 5 in Science, a single mutation at a hemagglutinin site, called 226L, would be enough to change the specificity of the virus from the avian type to the human type. Many scientists believed that at least two mutations were necessary. A change based on a single mutation “ means the probability of this happening is higher,” says Jim Paulson of Scripps Research, one of the authors.
A case more worrying than the others in Canada
Recently, the case of a Canadian teenager, who neither works nor lives near farmed animals, particularly alerted the scientific community. The boy consulted at the beginning of November for an eye infection, then for a cough and fever. He was hospitalized with a serious lung infection. “Viral genome sequences released last week suggest the teenager is infected with an H5N1 avian influenza virus carrying mutations that could enhance its ability to infect human airways,” explained the journal Nature on November 20. Namely: two possible mutations which could improve the ability of the virus to infect human cells, and another which could allow it to replicate more easily in human cells. He is believed to have been infected with a mixture of viruses that currently affects poultry or waterfowl in the region, a subtype called D1.1. During genomic sequencing, some replications of the virus were mutated to adapt to humans and others were not, suggesting that the virus may have mutated in the adolescent and that he was not infected. by this mutated form.
2024 marked a turning point on a global scale in the avian flu epidemic which now affects many species of mammals, including domestic species associated with human infections. However, “the bovine genotype seems quite stable and could persist for some time. It’s the D1.1 that worries me,” points Mike Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota Twin Cities, to Science.
Source: Nature, Science, Pasteur Institute, Public Health France
