Avian Influenza A H5N1—Situation in Early 2025
by Prof. Herve Fleury, MD-PhD—University of Bordeaux, France & Ventum Biotech, Boston, Massachusetts
Picture Source: CIDRAP
Wild birds are the ancestral reservoir of influenza A with a wide variety of subtypes (H1, H2, H3, H4, etc.). Humans are infected with human influenza A viruses; when two influenza A viruses, one avian and the other human, meet in the same animal, they recombine and a new human influenza can emerge: for example, the Hong Kong flu in 1968 was the result of a recombination between the Singapore flu of 1957 and a strain of duck influenza virus with the H3 pattern. The question that was asked until 1998 was the possibility for a "pure" avian virus to infect a human. This was confirmed in Hong Kong in 1998 with a child infected with H5N1 avian influenza from chickens.
If we focus on H5N1, this virus, which originated in China and Southeast Asia, was transported to Europe by wild birds; then it reached the American continent and, using north-south avian air channels, reached Patagonia and South Antarctica. Along the way, the virus was transmitted from wild birds to domestic birds and then to marine mammals (seals) and domestic mammals (pigs, cats, etc.).
The situation in the USA
A. Epidemiology
In the USA, where research and surveillance are of a high level, virological data have highlighted the contamination of wild birds and domestic bird farms (93 industrial farms as of February 6, 2025—recent example of an Indiana farm with 2.8 million birds), then cows first in New Mexico and then in Minnesota and Texas before being observed in other states (16 states at the beginning of 2025 with 959 reported infections); at the same time, the contamination of domestic cats and mice has increased and the main route of transmission has been highlighted (unpasteurized milk from infected cows); histological studies have shown the presence of the influenza virus in the mammary tissue of cows; cats, on the other hand, have a noisy pathology with encephalitis (detection of the virus in the central nervous system). Other mammals have been infected in the USA: wild cats, wild canine, bear, racoon, skunk, rodents. The virus has also been detected in pigs (first cases reported in Oregon in October 2024), which is important data insofar as this domestic animal is considered to be the "go-between" of recombination between avian and human strains at the origin of pandemic strains (e.g. AH1N1 pdm 2009).
The virus can be transmitted to humans; 67 human cases of avian influenza have been noted in the United States, mainly as a result of contamination from cows; most infections were clinically mild, including conjunctivitis; however, one death was reported in a 65-year-old man in Louisiana (contamination from poultry). A CDC study in November 2024 shows that 7% of infected herd farmers have antibodies against H5N1. In Canada, a severe case was observed in a British Columbia teenager with ARDS (Acute Respiratory Distress Syndrome) and resuscitation; The source of contamination is unknown.
Finally, it should be noted that a new avian strain has just entered a duck farm in California: H5N9
B. Hypotheses and means of control
Thus, the H5N1 virus approaches humans via domestic birds but also mammals; the possibilities of transmission to humans will increase; cases are described on several continents; They are serious but few in number because the avian virus has difficulty passing from one man to another. So what would be the dreaded event? The first hypothesis is that the H5N1 avian virus would be adapted to humans with the initiation of a pandemic (this may have been what happened in 1918); second hypothesis, a recombination in a domestic animal (cat? pig? cow?) of H5N1 with a human H3N2 virus generating a new human strain carrying H5 (H5N2 ...) and a pandemic because the human virus is adapted to human-to-human transmission.
It should be noted that H5N1 viruses isolated from farmers in the USA carry the E627K mutation in PB2 (viral polymerase) which is a mutation of adaptation to mammals.
What are the means of reaction: first, the planetary monitoring of the circulation of H5N1 (and other important strains such as H7N9); the responsiveness of laboratory examinations (molecular techniques such as PCR) should be highlighted; more and more, particularly in the USA, laboratories and/or private companies are undertaking the search for the viral genome of the influenza virus in wastewater, a technique that was used for the SARS CoV-2 epidemic (recent example of H5N1 positivity in wastewater in Hawaii...).
Secondly, it is important to implement hygiene measures: control of milk, animal feed (recent contamination of cats by raw pet food obtained from the meat of domestic birds).
Precautions are advised for farmers in contact with potentially infected poultry and livestock; vaccination against A H3N2 and A H1N1 (to avoid recombination), wearing protective gloves, goggles and masks.
The preparation of vaccines against H5N1 and in fact against H5 because antibodies against H5 can neutralize an H5N1 strain; the USA has a federal H5N1 vaccine stock with cultured and inactivated virus; the company Moderna has introduced avian flu into its agenda with an H5 mRNA; HHS has just awarded $550 million to this company for the development of mRNA vaccines against H5 and H7 (a phase 1 trial with H5 is underway). Companies in continental Europe have also begun the preparation of a dedicated vaccine, while the British NHS has just made it a national priority. One element to be confirmed would be that A H1N1pdm infection in humans could be partially protective against H5N1. Finally, a complementary strategy would consist of vaccinating domestic birds and livestock to reduce viral circulation and spillover to humans.
It should also be noted that there are anti-influenza molecules: favipiravir, baloxavir, zanamivir, oseltamivir (to a lesser extent) that could have a wide use (with obviously the risk of resistance to be assessed during an epidemic).
We will therefore have tools to fight it; the race is underway and let's hope that the emergence of an H5N1 viral pandemic, which is becoming a plausible hypothesis, will not come too soon in our preparation. It is reasonable to estimate that the fight against an H5N1 pandemic should be more effective and faster than against SARS CoV 2 because we have tools and information upstream of the risk.
This is also the interest of global surveillance of viruses around the world with whistleblowers specialized in the field of emerging and tropical diseases.
References
– CIDRAP (University of Minnesota)
– US Centers for Diseases Control
– Emerging and Re-Emerging Viruses (HJA Fleury) Elsevier/Masson (in French)
April 24, 2024—Update on H5N1 Avian Influenza
If we focus on H5N1, this virus, which originated in China and Southeast Asia, was transported to Europe by wild birds and then transmitted to domestic birds (refer to our problems of H5N1 infection in ducks in the southwest....); then it reached the American continent and, using the north-south avian air channels, reached Patagonia and South Antarctica. Along the way, the virus was transmitted from wild birds to domestic birds and then to marine mammals (seals) and domestic mammals (pigs, cats, etc.); A few weeks ago, cows were infected in Texas (a farmer was infected from his herd).
Thus, the H5N1 virus is related to humans via domestic birds but also mammals; the possibilities of transmission to humans will increase; cases are described on several continents; They are serious but few because the avian virus has difficulty passing from one human to another. So, what would be the dreaded event? First hypothesis, an adaptation of the H5N1 avian virus to humans with the initiation of a pandemic (this may have happened in 1918); Second hypothesis, recombination in a domestic animal (Cat? Pig? Cow?) of H5N1 with a human H3N2 virus generating a new human strain carrying H5 (H5N2, etc.) and a pandemic because the human virus is adapted for human-to-human transmission.
What are the means of response: first, global monitoring of the circulation of H5N1 (and other important strains such as H7N9); the responsiveness of laboratory tests (molecular techniques such as PCR); the preparation of vaccines against H5N1 and indeed against H5 because antibodies against H5 can neutralize an H5N1 strain; the U.S. has a federal H5N1 vaccine stockpile with cultured and inactivated virus; The company Moderna presented last week in Boston its agenda with the preparation of an H5 mRNA; two companies in Europe have also begun the preparation of a dedicated vaccine. So, we will have tools to fight it; the speed race is underway and let's hope that the emergence of an H5N1 viral pandemic that becomes a plausible hypothesis will not come too soon in our preparation.
March 14, 2022—Avian Influenza: Where we are where we’re going
Influenza A viruses are present in humans and animals. Wild birds and bats are the reservoir of influenza A viruses, especially since they are chronic carriers. The variety of hemagglutinins (HA) and neuraminidases (NA), which are the targets of neutralizing antibodies, is very large in these animals; thus 18 HA and 11 different NAs were recorded from H1 to H18 and from N1 to N11; the H17N11 and H18N11 viruses were observed only in bats, all the others being described in wild birds.
These wild bird viruses (which are emitted by the contents of the cloaca and by respiratory secretions) can be transmitted to domestic birds (direct contacts, contacts through food sources and water reserves); a distinction is made between low pathogenic strains (LPAI) and highly pathogenic strains (HPAI); in farmed birds LPAI causes little pathogenic effect (especially in ducks); there can be a drop in appetite and egg-laying as well as feather bristling; HPAI can cause massive clinical damage (especially respiratory, digestive and nervous) of farms with a high percentage of mortality.
Current situation
Since the end of summer 2021, outbreaks of H5N1 HPAI avian influenza have been observed first on the Baltic and then in the Netherlands, Germany, Italy in wild birds and domestic birds (turkeys, ducks, chickens, laying hens); in France, as of February 16, 2022, there are about 400 outbreaks of infection, particularly in the Landes and the Basque Country.
The fight against avian influenza in birds
In birds, it is impossible to control the circulation of wild birds that are the basis of epidemics during their migrations. Consequently, the action to be taken is, from the signal given of an infection in a wild bird in a given area, the claustration of domestic birds avoiding contact with wild birds. If the infection begins on a farm, slaughter is the rule; but other factors of contamination must be taken into account, these factors being related to human activities: movement of infected animals from one area to another by vehicles, transport of viruses via contaminated clothing and boots not or insufficiently disinfected, contamination of the vehicles themselves (wheels, tires, tailgates) ; it is very difficult to control such an epidemic.
Vaccines against H5N1 in particular exist (inactivated or recombinant vaccines) that can be used on farms; like the SARS CoV 2 vaccine, they do not prevent infection of a herd but decrease mortality and viral circulation. They should be used in addition to enhanced general hygiene methods. Note that a recombinant H5N1 vaccine can be given as an aerosol to chicks. Such vaccines are used in China, Vietnam, Mongolia and Egypt. In France, vaccination is allowed only in wild birds in zoos when they cannot be confined.
From a virological point of view, it is obvious that the monitoring of strains and their molecular characterization must be carried out at the global level in wild and domestic birds.
Avian influenza in humans
Human influenza A viruses that cause influenza pandemics have been defined as H1N1 (Spanish flu of 1918), H2N2 (Singapore), H3N2 (Hong Kong) and H1N1pdm of 2009. The origin of human influenza A pandemics is mainly related to the recombination in an intermediate animal (pigs) of human and avian influenza viruses, recombination being facilitated by the fact that influenza viruses have a segmented genome; thus H3N2 would have been obtained by recombination between H2N2 and an avian virus with a different HA that became H3 in the new emerging virus in humans. It can be imagined that the potential for the emergence of new subtypes of HA and NA in humans from the avian reservoir is very high.
An important issue concerns human infection with avian viruses; this has been described for H5N1 (first cases in 1997 in Hong Kong) and H7N9 in particular; it is rare but very dangerous since mortality is around 50%; human-to-human transmission is difficult but the fear is the adaptation of an avian virus to exacerbated human-to-human transmission leading to a pandemic; It should be noted that treatments exist against these influenza viruses: these are neuraminidase inhibitors (oseltamivir, zanamivir); it should also be remembered that the resistance of the influenza virus to this class of antiviral drugs has been objectified in some treated patients.
Of course, we will ask ourselves the question of vaccination in humans. The U.S. federal government has stockpiled an inactivated H5N1 vaccine developed in Pennsylvania by the French company Sanofi; this vaccine would be used in the event of a declared human H5N1 pandemic.
December 7, 2021—Avian Influenza: What if the next pandemic came from intensive farming?
Article by L’Éxpress, published by Yohan Blavignat on December 4, 2021
The Covid-19 makes us forget that another pandemic is breaking out all over the world. Avian influenza circulates massively in the shadow of valailles farms. At the end of November, a first outbreak was detected in France in a laying hen farm in Warhem (north) after an "observation of abnormal mortalities," according to the Ministry of Agriculture (France). The government had, however, anticipated by ordering a few weeks earlier, the confinement of birds throughout the territory due to the multipliocation of cases outside good borders among migratory birds. The trauma of the winter 2020 epizootic has not faded. The disease had then spread like wildfire in the farms of the South-West and was only stopped at the cost of the slaughter of more than 3.5 million animals. The dreaded scenario could happen again.
Since May, outbreaks have been detected in more than 40 countries. And nearly 16,000 cases of domestic and wild birds have already been reported in October alone, "which suggests an increased risk of curculation of the virus," worries the World Organization for Animal Health. In addition to the economic cost for professionals in the sector, the prevalence of the virus worries scientists, who fear depletion in the human population. This is what happened last year. In December, in a gigantic farm near the city of Astrakhan in southern Russia, 101,000 chickens passed out before dying. The cause is a relatively new strain, H5N8, which forced the authorities to hastily slaughter 900,000 other birds as a preventive measure. And the affair did not end there: out of 150 workers on the farm, seven were found to be prtors of the disease. These are the first known cases of transmission of H5N8 to humans.
According to scientists, there are a total of eight avian influenza fans, all capable of infecting or even killing humans. Considered to present risks of greater severity than Covid-19, they circulate regularly in industrial farms around the world, going almost unnoticed. This year, a wind of concern has been blowing from China since mid-October, where the H5N6 strain, first identified seven years ago, has infected 50 people –most being workers in poultry farms. This suggests that H5N6 is gaining ground, mutating, and could become extremely dangerous. So much so that the Chinese Center for Disease Control and Prevention calls it a "serious threat."
Adaptation or recombination: The two feared scenarios
"In the short term, there is no zoonotic risk, tries to reassure Jean-Luc Guérin, professor at the National Veterinary School of Toulouse, specialist in poultry farming and avian pathology. This form of influenza is perfectly suited to birds, especially with ducks. However, if we let this virus thrive for years in farms, we run the risk of seeing it become dangerous for humans." A point of view shared by Hervé Fleury, emeritus virologist at the CNRS: "In the event of infection in humans, a mortality rate of around 40 to 50% is observed. For the moment, avian influenza does not exist. has no pandemic capacity, and human-to-human transmission remains very low, without our knowing the exact reason."
The researcher fears two scenarios: an adaptation of the H5N8 strain to humans by dint of circulating within farms; or recombination of the virus with H3N2, human influenza. The case of influenza A (H1N1) in 2009 remains emblematic in this respect, since it turned out to be a recombination of three types: avian, human and swine! "It is a mosaic chimera which has adapted to the ecosystem in which it was evolving," explains Francois Renaud, research director at the CNRS and biologist in the evolution of infectious diseases.
Capacities for evolution and mutation which, according to scientists, should make us rethink the concept of intensive breeding: its principle promotes the circulation and mutation of viruses. "We must take into account the fact that the H5N8 virus will undoubtedly settle for many years to come. This danger is a real challenge for our outdoor poultry production systems," Jean-Luc Guérin still judges. So how can we hope to contain this epizootic? And the next ones? The question is worth the answer. In its hypotheses on the origins of the Covid, the WHO still suspects the coronavirus to come from giant farms in Southeast Asia. It was already there, in these buildings crowded with poultry, that, in the middle of the 2000s, a certain H5N1 had appeared.
March 1, 2021—What we know about the first transmission to humans of Avian Influenza H5N8
Russia announced that it had detected the first case of transmission to humans of the H5N8 strain of bird flu.
The Russian health agency Rospotrebnadzor said that it had detected “the first case of a person's infection with the group A virus, avian influenza H5N8,” particularly virulent. The World Health Organization (WHO) considers the discovery “important.” Appeared in France in 2016 in poultry farms in Tarn and Pas-de-Calais, this strain has long been perceived as “harmless" to humans.”
Hervé Fleury, virologist and emeritus researcher at the CNRS also serving on Ventum's Scientific Board has been warning about the virus' evolution; he told L'express in their article that the H5N1 virus had also passed to humans, as had the H7N9. "The barriers between species are not as severe as one would think" he added.
