Bird flu: Milk testing is now mandatory in the USA to check for H5N1

What’s happening on US farms doesn’t just provide material for westerns or family dramas: virologists all over the world are currently keenly interested in what exactly is going on in American stables. In March 2024 it was observed for the first time that bird flu virus strains also infect cows. The number of herds affected is currently 720 increasedthere are more and more every week.

Hundreds of thousands of animals thus become breeding grounds for the extremely mutable influenza viruses, perhaps for the next pandemic. This concern has plagued virologists for months – and has now prompted US authorities, including the US Department of Agriculture, to raise theirs National Milk Testing Strategy to start. Milk tests have been ordered nationwide: When cows are infected with the new H5N1 strain, the viruses appear in the raw milk. The aim of screening milk tanks is to identify new sources of infection more quickly.

One mutation is enough

The program begins now in California, Colorado, Michigan, Mississippi, Oregon and Pennsylvania. In the hope, on the one hand, of being able to better assess and monitor the infection process and, on the other hand, to contain the epidemic in the country. Finally – or is it already too late? The circulating strains only need to change their appearance slightly to suddenly start preferring human cells over those of cattle, a recent study shows. One mutation is enough.

In addition to detections in dozens of bird species, H5N1 has already been detected in samples from more than 200 wild mammal species. What is more dangerous, however, is that bird flu is circulating in cattle herds in 15 US states, according to the Centers for Disease Control and Prevention, CDC. document. There the pathogens multiply in thousands of mammals that farm workers come close to every day.

Close contact, such as when using a milking machine, naturally increases the likelihood that H5N1 will spread to humans. With increasing risk that the avian influenza viruses adapt to this new type of host. “The situation in the USA with the high number of cases in wild birds, poultry and also cattle is increasingly leading to ‘spill-over infections’ in humans,” explains Martin Beer, head of the Institute for Virus Diagnostics Friedrich-Loeffler-Institut (FLI) on the island of Riems.

In order to keep the number of human infections as low as possible, it is absolutely necessary to control cases in dairy cattle and poultry as quickly and as well as possible. Close early detection and surveillance measures, including genomic analyses, are necessary in all areas, Beer told the “Science Media Center” in Cologne. “Much more effort should be made here, especially when it comes to beef. People who work in infected companies must definitely be protected accordingly,” emphasized Beer.

“Spill-over infections” have already occurred several times in the USA: In 35 of the 58 cases so far in 2024, people were infected with H5N1 from cows, report the CDC. In 21 cases, poultry was considered the source of infection; 49 states have already registered outbreaks in poultry farming. In two cases, the origin of the virus remained a mystery.

For example, it is unclear how a child in California became infected with bird flu. Although a particularly large number of herds are affected in the region, the child had no contact with cows. The one with different viruses infected child suffered only mild symptoms, and the family, which was also plagued by respiratory infections, was spared from H5N1. Nevertheless, this case alarmed the authorities.

H5N1 has not yet been transmitted from person to person. And the risk of infection with the new strains is still considered low. But that can change alarmingly quickly, as research shows Scripps-Institut iIn La Jolla, California, there are fears: A mutation at a crucial point allows the pathogens of the animal disease to bind preferentially to receptors on human cells. This doesn’t just happen under laboratory conditions, but can occur in nature – as evidenced by Canada’s first case, which has been bothering the authorities since the beginning of November: In British Columbia, a teenager became seriously ill with bird flu.

Canada’s first case

The child initially came to the emergency room with conjunctivitis, cough and high fever, and a week later he was on a drip and given antiviral medication intravenously. The teenager was still in critical condition, it was said on November 26 when the provincial government released its final report presented.

It also said that no bird flu virus could be found in any of the samples examined – from people, domestic and wild animals, water, soil: “While it is reassuring that no further cases were identified, the authorities were also able to identify the source of the boy’s infection Don’t definitively identify people.”

Two children, around 1,500 kilometers apart, two mysterious infections. In the Canadian case, the source was likely a bird, not a mammal. The teenager was infected with a strain of influenza currently circulating in wild birds and poultry in British Columbia (clade 2.3.4.4b, genotype D1.1). Additionally, the viral genome is more similar to pathogens found in wild birds rather than those linked to outbreaks on poultry farms. And the geneticists discovered something else: a mutation in the receptor binding site.

Just a small change, but one of great importance. The corresponding position 226 in the membrane protein hemagglutinin (the H in H5N1) influences which host cells the influenza viruses prefer. And it is the same one that researchers led by Ting-Hui Lin and Ian Wilson at the Scripps Institute noticed. They experimented in the laboratory with an H5N1 virus strain from Texas, with which a human was first infected from a cow in the spring.

It’s worth mentioning that they didn’t work with mutated viruses, but rather just changed the hemagglutinin: to imitate genetic mutations that can occur naturally and then determine how well or poorly the modified membrane protein binds to different receptors. “This type of research helps us understand which mutations to look out for and how to respond appropriately,” explains Wilson.

Lo and behold: replacing just one amino acid in hemagglutinin switched the bird flu virus’s binding preference to human receptors, reported the Scripps team is currently in the journal “Science”. The binding is more robust than, for example, that of the pandemic virus H1N1, which caused a stir worldwide in 2009 as “swine flu”. A second changed amino acid in the membrane protein increased binding; However, in order to be able to assess the infection potential, further data would be needed.

Stronger bond

The “Science” study confirms assumptions that a receptor switch is possible, explains Martin Beer: from the avian to the human receptor type. A second mutation strengthens this switch even further. The fact that an H5N1 virus of clade 2.3.4.4b with similar changes was found in the seriously ill teenager in Canada proves “the practical relevance of the study”. Previous adaptations of H5N1 in humans were limited to the polymerase, which increased its proliferation in the mammalian host.

“Adaptations to the human receptor are new in this clade,” emphasizes Beer, referring to the Canadian case. And with reference to the study, the FLI Vice President explains: “Two adjustments in the hemagglutinin seem to be enough to enable complete adaptation.” This should definitely be taken into account when assessing the risk.

Binding to the receptor is a crucial step for transferability. Nevertheless, the pathogen would have to change even more to turn into a pandemic virus. In addition to the cell receptor, there are other “hurdles” to overcome, such as innate immunity. “Receptor mutations alone are no guarantee that the virus can be transmitted from person to person,” says study leader Ian Wilson.

Given the increasing number of spillover cases, the Scripps researchers say their findings underscore the need to proactively monitor the evolution of H5N1 and similar avian flu strains.

The current infection situation in the USA requires close monitoring, says Martin Schwemmle from the Institute of Virology at the University Hospital of Freiburg. This is the only way to detect at an early stage whether further mutations are occurring that potentially endanger people.

This is particularly important in view of the upcoming flu epidemic. Then H5N1 viruses meet human influenza viruses – and can exchange genetic material. It is quite reassuring that viruses of the clade 2.3.4.4b in Germany have so far concentrated on plumage and are not rampant among mammals. Things are different in the USA, where it is high time to stop the chains of infection in the stables.

As head of department, Sonja Kastilan is dedicated to “knowledge” – and pursues topics from medicine and life sciences: from Aids from evolutionary biology and genetic analysis to stem cells and Zika.