This is the story of a virus that we know well, identified for the first time in southern China in 1996 which, twenty-eight years later, is making headlines again. Influenza A (H5N1), better known as “bird flu” or “avian influenza”, has since conquered the planet and is now worrying scientists for its pandemic potential. Since 2020, the number of outbreaks in birds has exploded and more and more species of mammals are affected (walruses, polar bears, seals, sea lions, etc.). Last month, cows and goats joined the list. It is ultimately in the United States that the situation is getting out of hand in recent weeks. For the first time, an influenza A epidemic affects cattle in nine American states. In Texas, a breeder was even infected in early April after being in direct contact with an infected cow. Latest information to date: traces of H5N1 have been detected in pasteurized milk sold in the United States, making this country the epicenter of an avian epidemic that has become animal. All of these elements led the World Health Organization (WHO) to express its “enormous concern” on April 18 about the increasing spread of this strain of avian flu to new species, including humans. How did we get here ?
New elements on the origins of the evolution of the epidemic were relayed at the beginning of the week by the magazine Nature. According to a preliminary analysis of genomic data conducted by the United States Department of Agriculture (USDA), this new highly pathogenic strain of influenza A (H5N1) has been spreading silently in American livestock farms “for several months.” This publication comes in a climate of distrust among scientists, who have criticized in recent days the lack of transparency of the American authorities. The outbreak would, in fact, likely have started when the virus jumped from an infected wild bird to a cow, probably around late December or early January. However, scientists, like Malik Peiris, virologist and professor at the University of Hong Kong, feared “low noise” circulation in several regions of the world, which could allow it to evolve. Because this avian flu epidemic does not resemble what we have known until now: “A new strain has actually mixed with local viruses in the United States and has the particularity of multiplying extremely well in the udders of cows”, specifies Malik Peiris. This explains the numerous outbreaks in cattle farms, which initially surprised experts because, in these species, the virus receptors in the upper respiratory tissues are not optimal for H5N1. “On the other hand, we do not yet know precisely how this pathogen is transmitted between cattle,” continues the virologist.
Scientists now fear that H5N1 will be transmitted more easily to humans, or even, in a dark scenario, that it will acquire the capacity to be transmitted from human to human. “There is strong concern about its spread among dairy workers given the high level of virus present in the milk of infected cows,” says Seema Lakdawala, a virologist at Emory University in Georgia. If a person were to be splashed in nose or in the eyes and become infected, this would give the virus new opportunities to adapt and transmit between humans.
The dark scenario
However, if cows can produce numerous viruses and are regularly in contact with humans, it would take a bad turn of fate to see such a hypothesis arise. “Scientists are concerned that H5N1 may have adapted to spread efficiently among mammals, particularly through the respiratory route, but this would require a profound change in the way it uses sialic acid. [NDLR : qui permet aux virus de type influenza de pénétrer dans les cellules humaines, à l’instar de la protéine Spike pour le Sars-CoV-2] to bind to human receptors, coupled with an adaptation of certain proteins necessary for such a purpose. So far, no evidence of such an evolution has been detected,” says Daniel Goldhill, evolutionary virologist at the Royal Veterinary College in Hatfield, United Kingdom.
However, in its genomic analysis released this week, the USDA revealed that the virus is actually “multi-host.” We have in fact observed transmission from bird to cow, from cow to cow, from cow to bird, but also from cow to cat or from cow to human. All this suggests that H5N1 could have found other transmission routes than those previously imagined by specialists. But also that it has evolved a lot in recent months. Among these mutations are changes to a viral-protein section that scientists have linked to a possible adaptation to spread in mammals. What, again, is cause for concern. Especially since a mystery remains. If the case of the Texan infected in early April seems benign – he only suffered from conjunctivitis – his viral genome does not include some of the signature mutations observed in cattle. “It’s a conundrum for everyone,” says David Goldhill. One hypothesis is that this person was infected by a distinct viral lineage, which would have contaminated cattle that were not swabbed. Another scenario, less likely but which cannot be excluded, is that this breeder was infected directly by a wild bird.
The enigma of the human host
Given the current state of knowledge, however, experts are not being too alarmist. H5N1 continues to spread among mammals, of course. We risk seeing the appearance of sporadic cases, both in animals and in humans, of course. On the other hand, we are not observing a major modification of the virus which would lead to a higher risk of pandemic than two or three months ago, scientists say. Additionally, although the H5N1 strain has killed millions of poultry during the current wave, affected cows have not become seriously ill at this point. Furthermore, the risks appear non-existent in the event of consumption of pasteurized milk: this process in fact destroys the virus, even if it does not remove all traces of its presence. Finally, the strain currently circulating in the United States is, in any case, different from those present in Europe. Furthermore, to date there is no circulation of this influenza virus among French cattle where the level of risk, described as “moderate” since mid-March, was even lowered to “negligible” at the end of April, after a season where the pathogen circulated less and farmed ducks were vaccinated. However, caution is required. This Tuesday, April 30, Wenqing Zhang, who heads the global influenza program at the WHO, affirmed that, given that the virus is carried in particular by migratory birds, “the risk certainly exists that cows of other countries are infected.
Because the scenario of a spread of H5N1 in humans remains a worrying prospect. “This is a much more virulent pathogen for humans than Covid-19. Such a pandemic could make Sars-CoV-2 appear very benign,” specifies Malik Peiris. What we know today is that this virus can cause an infection in humans if it is found in two very specific places: on the conjunctiva of the eye – and it is a benign infection – or at the level of the pulmonary alveolus, deep within the lung. In this second case, the infection can be serious. Of some 900 human cases of H5N1 infection recorded over the past twenty years by the World Health Organization (WHO), half have been fatal… “The longer this epidemic continues, the greater the risk that unexpected adaptations of the virus will occur , for humans or for other species, is high”, warns David Goldhill. To prevent such a slippage from happening, scientists are calling for rapid and drastic measures to be taken. “To avoid many infections in humans, why not make it mandatory for dairy workers to wear a mask, or force livestock not to leave the farm to reduce the spread of the current epidemic? asks Seema Lakdawala. “We have to move quickly from now on!”
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