Animals and humans share about 300 infectious diseases, and new ones appear every year. According to data of the World Organization for Animal HealthIn the last few years, about 75 % of new emerging human infections are of animal origin. From April 27th to 30th, Barcelona will be the venue for the congress World Society of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). One of the topics to be discussed is the threat of a new pandemic.

No one doubts that it will happen, the problem is that we do not know what will cause it or when. Years ago, the WHO already defined disease X as a global health threat. The causative microorganism would probably be an easily airborne virus, very virulent and "new" to our immune system.

The vast majority of scientists thought that the most likely candidate would be a new influenza virus, but the SARS-CoV-2 coronavirus beat us to the right. Although the threat of a new coronavirus remains latent, the influenza virus is still the candidate most likely to cause the next pandemic.

The champion of variability
The influenza virus or influenza belongs to the family of the Orthomyxoviruses. In fact, there are four genetically distinct types (A, B, C and D). In humans, influenza A is the most common; influenza B appears every 2-4 years and is usually less problematic; influenza C is rarer and usually causes mild infections; and subject D viruses affect livestock.

The virus is surrounded by a membrane, or envelope, and has a genome contained in eight RNA fragments with information for ten proteins. In influenza A virus, two of these proteins are called hemagglutinin (abbreviated with the letter H) and neuraminidase (N). So far, 18 different types of H and 11 types of N are known. The one with the H of subject 1 and the N of subject 1 is called H1N1; the one with the H of subject 1 and the N of subject 2, H1N2... and so on up to H18N11, depending on the possible combinations.

This virus varies in two ways. When it replicates its genome, it can undergo errors or mutations in the H and N genes, which give rise to subtypes or strains that change over time. They are the cause of seasonal influenza epidemics and the need to renew vaccines every one or two years. For this reason, vaccines are prepared with a cocktail of the viruses that were transmitted in the population the previous year.

In addition, as its genome is made up of several segments, the virus can mix or recombine when different strains infect the same animal at the same time. For example, this can occur in a pig infected by a human influenza virus from subject H2N2 and another from birds from subject H3N8. Within the pig, the new H3N2 strain is produced - which takes the H3 from the avian virus and the N2 from the human - and could infect and multiply in our species.

The pig would therefore act as a real natural essay tube. This explains the emergence of new types of the virus, which can cause pandemics because the human population has never been exposed to the new pathogen, has no defenses against it and can be easily transmitted.

Influenza are bird viruses
The natural host of influenza viruses is not the human being, but aquatic birds such as ducks or geese, the great reservoir or natural storeroom of most influenza A subtypes. These birds can spread the pathogen and transmit it to domestic birds, but can also infect pigs, horses, bats, domestic animals, marine mammals... and, of course, humans.

Normally, influenza viruses capable of binding to receptors on human cells are usually of the H1N1, H2N2 or H3N2 types. It is therefore a zoonosis: a disease of animals that passes to humans.

Influenza pandemics
According to data of the WHO, seasonal influenza can affect up to one billion people a year. It causes between 290,000 and 650,000 deaths per year due to complications arising from the viral infection, especially in children under five years of age.

There have been four pandemics of this disease so far: the 1918 flu strain, which was of subject H1N1 and of avian origin and caused the largest flu pandemic in history, with 20-40 million deaths worldwide; that of 1957, originated from the emergence of a new pathogen of subject H2N2 by recombination between bird and human viruses; that of 1968, which caused a new H3N2 strain also originating from the mixing of bird and human viruses, and the pandemic threat in 2009 from an H1N1 strain whose origin was recombination between swine influenza viruses, bird and human strains. In this case, unlike the H1N1 of 1918, it caused "only" about 200,000 deaths.

The H5N1 virus: an influenza pandemic in birds...
At the end of the 1990s, the H5N1 virus appeared in China, causing great mortality in wild birds and occasional cases in humans. Subsequently, it reached Europe through migratory birds and began to circulate massively and diversify. Since 2020, a very virulent variant of H5N1 (called 2.3.4.4b) has been detected and has infected many birds: ducks, geese, gulls, chickens, pelicans, swans, vultures, eagles, owls, crows... Species that previously did not suffer from the disease have suffered mortalities never seen before.

In addition, not only has issue significantly increased, but also the spread of outbreaks in Asia, Europe, Africa and the Americas. Hundreds of millions of birds have been culled in the USA and Europe. The H5N1 virus can be classified as a true pandemic in birds, which is called a panzootic.

... that has jumped to mammals
In recent months, H5N1 has also been detected in many mammals: badgers, bears, cats, lynxes, otters, raccoons, dolphins and porpoises, ferrets, mink, foxes, leopards, pigs... In October 2022, an outbreak was identified in Galicia (Spain) in a mink farm and nearly 50,000 animals had to be culled. A few weeks earlier it had been detected in gannets and gulls, so the virus was able to "jump" from these birds to mink. The pathogen had a mutation in a polymerase gene that could facilitate its replication in mammals.

In 2023, there were massive outbreaks in seals and sea lions in Scotland, Peru, Brazil, Uruguay and Argentina, with unprecedented mortalities. Outbreaks have also been described in domestic cats in Poland and South Korea. It has even been detected as a cause of mortality in birds and wild mammals in the Antarctic region.

All this shows that it is not a sporadic jump from birds to mammals, but a sustained transmission. This confirms the transmission of the H5N1 virus among mammals, which is unusual. It may not only pose a public health threat, but also a problem for the preservation of biodiversity.

And now also in cattle
Last March, U.S. authorities announced that the H5N1 virus had been detected for the first time in dairy cattle in eight states. It is the same subject 2.3.4.4b that has spread across the globe. Although, as mentioned above, it is highly pathogenic in poultry, affected cows only suffer from lack of appetite and reduced milk production. A worker on one of the farms has been confirmed infected, but the only symptom has been conjunctivitis. Tests have found no changes that would make the virus more transmissible to humans. Fragments of the virus have also been reported in pasteurized milk samples.

Very sporadic cases have been reported in humans. Since the first detection in 1999 in China, about 900 cases have been reported, always in individuals at contact in close contact with birds or other animals. Fortunately, this virus is not transmissible from person to person. However, in certain situations, its lethality in humans can reach 50%. Let us remember that virulence and transmissibility are different things.

Much has to change to be a real threat
The H5N1 virus is increasingly spreading in birds and mammals. But for it to become pandemic , it should become more capable of airborne transmission between humans, improve its ability to enter our cells and multiply, and be able to evade the immune system.

For all this right combination of mutations to happen is difficult... but not impossible. It is a virus that has been warning us for some time, it is getting closer and closer. The fact that it is being isolated from more and more mammalian species and is beginning to be transmitted increases the chances that it will change or recombine.

As the human population expands and the environment deteriorates, the relationship between people and animals is altered and new opportunities for contact and disease transmission are created. All of this underscores the importance of a strategy of partnership and communication between all sectors involved in human, animal and environmental health care: One HealthOne Health or Global Health.

It is necessary to continue to monitor influenza viruses closely and to continue to develop new therapies and universal vaccines against it, because it remains a real threat.

This article was originally published in The Conversation. Read the original.