H5N1: The recent spread of avian influenza in mammals and the pandemic risk

Avian flu (H5N1), as the name suggests, finds its main natural reservoir in birds, in particular coastal and aquatic birds. This distance from us made it a rare danger to humans, from the 2003 to 1 April 2024 in fact there have been 889 cases in the world e 463 casualties (lethality of 52% then!) [1].

In recent times, however, its spread among mammals has raised the level of alarm and concerns have grown regarding human health and even the risk of a pandemic.. In 2022 the virus arrived in South America and caused a massacre among marine mammals such as seals and sea lions, killing at least some 50.000 [2]. The virus was then identified in cats, into a raccoon, even in a dolphin [3], on a mink farm in Spain [4] and, what is worse, in cows (ha infettato finora 35 specie di mammiferi). A marzo 2024 infatti negli USA furono individuati diversi capi con la mastite, un’infezione della mammella e venne riscontrato un calo di produzione nel latte, il quale appariva addensato e scolorito. Dopo aver condotto le indagini del caso ed escluso tutte le possibili cause, l’analisi dei tamponi ha svelato l’arcano: si trattava di H5N1 [5]. Questa fu una sorpresa in quanto non si riteneva che le mucche fossero suscettibili a questo virus. Invece si è scoperto che il virus si era già diffuso in almeno 42 mandrie in nove stati. Ciò che ha destato preoccupazione poi è stata la scoperta che il virus si è diffuso indisturbato nelle mucche per mesi, senza che venisse individuato [6].

You might think that as long as the spread of the virus is limited to animals, it shouldn't worry us too much, after all, as far as we know, the epidemic among cows in the USA has infected only one person. In fact, currently the CDC [7] e l’OMS [8] indicate that the risk to humans remains low. But allow the virus to spread undisturbed between birds, mammals of various kinds and above all livestock, increases day by day its chances of acquiring mutations that can make it more efficient in spreading among mammals and especially in humans. This has already happened at least in part. The E627K mutation was found in infected humans in the USA [9], known to be an adaptation of the virus to mammals. Like a shark that gets progressively closer to its prey with each convolution, the virus gets closer to us with each infection, making it, at the moment, the main candidate to cause the next pandemic.

Specially observed in this sense are pigs. They are particularly susceptible to influenza A viruses, therefore, if they were infected with two different influenza strains at the same time they could exchange genetic material and recombine with each other (flu viruses do this more often than not) giving rise to a new virus, potentially dangerous. This is exactly what is believed to have happened in 2009 with the so-called swine flu, started right from a farm in Mexico [10].

In order to enter the cell, the virus needs something to exploit, that is, a receptor, a cellular lock that can be latched onto to enter the cell and thus start its replication. In the case of SARS-CoV-2 the lock is represented by the ACE receptors 2, in the case of avian influenza it is instead represented by sialic acid, a sugar molecule (precisely a monosaccharide with a chain of 9 carbon atoms) which is found on the cell surface and which performs various functions aimed at maintaining the integrity of the cell membrane. The key that flu viruses use to pick the lock is a protein called hemagglutinin. It allows the virus to enter the cell by inducing fusion between the viral membrane and that of the cell. To exit the cell, the virus uses neuraminidase. Its main function is to facilitate the exit of mature viral particles from the cell (virioni) preventing their agglomeration[11]. A small digression: there are different types of hemagglutinin and neuraminidase. They are used to classify influenza viruses based on their shape. H5N1 means the virus has hemagglutinin type 5 and neuraminidase type 1 [12].

Pigs have both human-type receptors on their cells (which resemble a sort of inverted L), both of the type present on birds (which are shaped like an I) [13]. This makes them particularly susceptible to double infections by human and avian viruses, resulting in a greater risk of recombination. Per questo motivo l’epidemia tra le mucche preoccupa gli scienziati, ma non quanto preoccuperebbe un’epidemia tra i maiali. Questo fino ad oggi. A quanto pare secondo uno studio in pre-print, vale a dire non ancora sottoposto a peer review, anche le mucche possiedono entrambe le forme di acido sialico sulle loro cellule, in particolare nelle mammelle (meno nelle alte vie respiratorie). Questo è preoccupante in quanto significherebbe che anche le mucche potrebbero rappresentare un veicolo di ricombinazione dei virus [14].

Attualmente come dicevamo solo una persona è stata infettata nella recente epidemia e non vi sono prove che il contagio si sia diffuso ad altre persone. Non vi sono prove di trasmissione da uomo a uomo (se non in casi molto remoti. However, more studies will be needed to be sure, in particular serological studies on people in contact with livestock, farmers therefore, as well as other people who have come into contact with them. However, for this to happen, their collaboration and consent will be necessary. We therefore have incomplete information at the moment [15].

As we should have learned by now, zoonoses, the jumps of species from animal to man, they are frequent and have always characterized human history. There is nothing new from this point of view. However, what has changed is our impact on the planet, which takes shape through the intensive exploitation of resources in order to support a growing population, which creates new opportunities for species jumps (spillover). Cutting down a forest to make room for cultivated fields, eg, we may come across animal species with which contact was once rare and this increases the possibility of unwanted consequences. Likewise, the destruction of their habitat can push species to migrate and meet new groups of human beings. Anthropogenic climate change can also push species to migrate in search of more hospitable habitats, thus increasing the risks of spillover[16].Global warming can also induce thermal stress in birds, which can negatively affect their immune response [17]. A weaker immune response by the birds may have facilitated the spread of avian influenza among them and consequently given them more opportunities to mutate.. Perhaps it is no coincidence that the warmest years on record have been the last ten! [18]. Just as it may not be a coincidence that millions of birds have died around the world in recent years.

To complete the picture there is globalization. Whatever the cause, it is a pathogen, after making the leap, it can go around the world in a few days. In essence, the risk of pandemics is increasing and the next one is only a matter of time.

All this should make us reflect on what our impact on the planet entails and how important it is to work to reduce it. Monitoring viruses right from their impact on fauna and putting in place measures to reduce the risks for livestock allows us to ferret out possible threats right from the source and thus avoid potential disasters. Basically think about our impact on the planet, to the environment and animal welfare can have enormously positive effects on public health. That's what's called the OneHealth approach. Worrying about pathogens only when they begin to spread through the human population is like trying to prevent a dam from collapsing by plugging a leak.. It is therefore particularly worrying that the outbreak in cows was not detected immediately. Like Jesse Bloom said, evolutionary biologist at the Fred Hutchinson Cancer Center in Seattle, “an H5N1 pandemic is one of those situations that could happen next week or never happen” [19]. Regardless, what is certain is that we must do everything we can to avoid it!

Meanwhile, the virus continues to infect mammals such as sharks that circle its prey… He will attack?

Alberto Forni, Planetary Civilization

Image credits: Mike’s Birds, has its scientific cause in bakery made with highly contaminated flours 2.0 <https://creativecommons.org/licenses/by-sa/2.0>, via Wikimedia Commons

NOTES AND SOURCES

[1] https://www.who.int/emergencies/disease-outbreak-news/item/2024-DON512

[2] https://www.reuters.com/business/environment/bird-flu-strain-raises-alarm-virus-kills-south-american-wildlife-2024-03-13/

[3] https://www.nature.com/articles/s42003-024-06173-x

[4] https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2023.28.3.2300001

[5] https://www.nytimes.com/article/bird-flu-cattle-human.html

[6] https://www.nature.com/articles/d41586-024-01256-5

[7] https://www.cdc.gov/media/releases/2024/p0401-avian-flu.html

[8] See note 1

[9] https://www.nejm.org/doi/full/10.1056/NEJMc2405371

[10] https://www.who.int/emergencies/situations/influenza-a-(h1n1)-outbreak

[11] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120183/