Bird flu: where is the spread and why we must act now

The virus can also spread indirectly, through contact with contaminated surfaces or materials such as manure, egg containers, cages, farm equipment, shoes, clothing and hands.

Its resistance, especially at low temperatures, allows the virus to survive for a long time on contaminated objects, further promoting its spread. In addition, there is a risk of the virus being introduced into domestic farms through contact with wild bird droppings outside.

Human infections with avian influenza are rare, but can occur after direct or indirect exposure to infected animals, especially birds but also other mammals such as cows and cats, or to contaminated environments.

The main routes of transmission include contact with saliva, nasal secretions, faeces, blood or other body fluids (including milk from infected cows). Inhalation of viral particles in respiratory droplets or dust in animal environments is another mode of transmission. In addition, handling infected poultry carcasses and preparing chicken for consumption are additional risk factors.

It is important to emphasise that poultry and eggs, if properly cooked, and pasteurised milk are safe for consumption. Workers who have frequent contact with birds, poultry, waterfowl and cattle, such as veterinarians or those working in live animal markets, are at greater risk. People with compromised immune systems may also be more vulnerable to developing severe forms of the disease.

In birds:
Symptoms of highly pathogenic avian influenza (HPAI) in poultry include sudden death, loss of energy and appetite, decreased egg production, soft-shelled or deformed eggs, swelling and purplish discolouration of the head and legs, respiratory distress, nasal discharge, coughing, sneezing, twisting of the head and neck, motor difficulties and diarrhoea.

Low pathogenic avian influenza (LPAI) may cause mild symptoms such as respiratory distress, reduced egg production and diarrhoea, or show no signs at all. Infected wild birds may show no symptoms, but the often asymptomatic nature of the virus in wild birds and the variety of symptoms in poultry make early diagnosis difficult. Sudden deaths in poultry are an important warning sign.

In humans:
Symptoms in humans range from mild upper respiratory tract infections to severe forms such as pneumonia, acute respiratory distress syndrome (ARDS), shock and death. Common symptoms include fever (which may not always be present), cough, sore throat, muscle aches, fatigue, headache, stuffy or runny nose.

In recent cases in the US, conjunctivitis has been a prominent symptom. Less common symptoms include diarrhoea, nausea, vomiting and convulsions. Serious symptoms requiring immediate medical attention include difficulty breathing, high fever, confusion, altered mental status, severe fatigue, severe headache and neck stiffness.

More serious complications may include pneumonia, respiratory failure, ARDS, kidney damage, multi-organ failure, sepsis and encephalitis.

Strict biosecurity measures are essential to prevent the spread of avian influenza in poultry. These include controlling access to poultry houses, cleaning and disinfection of equipment, vehicles and footwear, and maintaining good hygiene. It is essential to prevent contact between domestic poultry and wild birds, especially waterfowl, and their droppings.

It is equally important to report the presence of sick or dead birds to the competent authorities. In case of HPAI outbreaks, culling all infected and exposed poultry is often the only way to stop the spread of the virus. Quarantine zones and restrictions on the movement of poultry and poultry products in affected areas are also established.

A rapid response, based on early detection, is crucial to contain outbreaks. The economic impact of culling on farmers is significant, highlighting the need for support and compensation.

To prevent infection in humans, it is advisable to avoid direct contact with wild birds and other animals that are infected or suspected of being infected. Animals should be observed from a distance and diseased or dead animals should not be touched. When contact with animals or contaminated environments is unavoidable, it is essential to wear personal protective equipment (PPE) such as gloves, masks and eye protection. Frequent and thorough hand washing with soap and water is essential, and avoid touching your face after contact with contaminated surfaces.

It is recommended to consume only pasteurised milk, poultry and well-cooked eggs. Seasonal influenza vaccination is useful to reduce the risk of co-infection. Travellers to affected areas should avoid poultry farms and live animal markets. Finally, public health messages should focus on practical and easy-to-take actions to protect oneself, addressing risk behaviours such as consumption of raw milk.

In recent decades, avian influenza has remained a constant threat, confined mainly to the world of wild birds and farmed poultry. Today, the situation is changing. The virus has started to infect an increasing number of mammals and, most recently, has been detected in dairy cattle in the United States. This has raised new questions about the ability of the H5N1 strain in particular to adapt to different hosts and the implications for the future.

Starting in 2020, the avian influenza landscape underwent significant transformations, when a new strain of avian influenza emerged HPAI H5N1, characterised by the HA 2.3.4.4b gene. Unlike previous variants, the 2.3.4.4b strain showed an extraordinary ability to adapt to wild birds, facilitating rapid global spread.

The emergence of this variant was not an isolated phenomenon, but rather the result of a process of genetic reorganisation, in which several type A influenza viruses exchange genetic material, leading to the formation of this particularly virulent H5N1 subtype. The virus' ability to persist and spread among wild bird populations has transformed avian influenza from a series of isolated outbreaks to an ongoing global threat.

LPAI and HPAI H7N3 avian influenza outbreaks were reported on turkey farms in the US in 2020. In Europe, the HPAI H5N1 strain, adapted to wild birds, rapidly spread to Africa, the Middle East and Asia. China reported several human cases of HPAI H5N6 infection, while in the UK, the HPAI H5N8 strain was detected in several wild species, including seals, foxes and swans. In addition, in Russia the virus was isolated in a poultry worker, although asymptomatic.

In 2021, the HPAI H5N8 virus was detected in seals in several European countries. Laos recorded its first human case of HPAI H5N6 infection, while in the Netherlands and Estonia the HPAI H5N1 strain was detected in wild fox cubs. In China, besides a considerable number of human cases of HPAI H5N6 and LPAI H9N2, the first human case of LPAI H10N3 infection was reported.

In 2022, H5N1 continued to spread, reaching sea lions in Peru and a mink farm in Spain. In France, the virus was detected in a captive black bear, while a human case was reported in the US, probably due to contamination. In Spain, two poultry workers tested positive, although asymptomatic. In China, there was one human case with a fatal outcome. A particularly worrying event was the mass die-off of Caspian seals, with hundreds found dead, fuelling fears of possible transmission between wild mammals.

In 2023, the H5N1 virus was detected for the first time in the Antarctic region. In Alaska, a polar bear died of the infection, while Brazil declared an animal health emergency in response to reported cases in wild birds. In Canada, a domestic dog tested positive, while human cases, including one death, caused by an older strain of H5N1 were reported in Cambodia.

In 2024, the virus made a further species jump from poultry and wild birds to mammals, particularly dairy cows in the United States. This event coincided with an increase in human cases in the country, especially among dairy and poultry workers, with generally mild symptoms. In addition, the virus has been detected in cats, with a possible link to consumption of raw pet food and suspected transmission between felines.

In 2025, the avian influenza epidemic continues to pose a significant challenge, especially in the United States. As of March, there were 989 dairy farms affected in 17 states, with California particularly affected. As for poultry, since April 2024, outbreaks have been detected on 336 commercial and 207 domestic farms, affecting more than 90.9 million birds.

New cases were confirmed on poultry farms in Illinois, Indiana, Kansas and Montana, while outbreaks of H5N1 were detected on turkey farms, live bird markets and domestic farms in several states. The World Health Organisation also confirmed that the virus is still active in the western Pacific region. 

In early 2025, a human case of avian influenza was identified in Ohio with a new viral genotype, named D1.3. This case was linked to prolonged exposure to infected poultry in an area heavily affected by H5N1 outbreaks. The D1.3 genotype, derived from the A3 strain introduced in North America in 2022, has undergone reassortment with local wild avian influenza viruses. Genetic analyses did not reveal any mutations that would compromise the effectiveness of existing antivirals or vaccines, nor any indication of an increased ability of the virus to spread among mammals. Currently, studies are underway to isolate the live virus and further investigate its characteristics.

The Centers for Disease Control and Prevention (CDC) continues to rate the risk for the general population as low, while it remains moderate or high for those exposed to infected animals or contaminated environments. Since April 2024, 70 human cases of H5 infection have been reported, of which 41 were associated with sick dairy cows and 26 with infected poultry. In three cases, the source of exposure was not determined. There was no evidence of inter-human transmission, and most cases showed mild symptoms, with conjunctivitis being the most common manifestation.

New developments in research and funding could be the key to successfully combating bird flu. The United States Department of Agriculture (USDA) recently announced significant funding of up to $100 million for projects aimed at combating bird flu in poultry.

In particular, the focus is on the development of new, more effective and safer vaccines to respond to this growing threat. Priority criteria for poultry vaccines include crucial aspects such as a good match with circulating viral clades, the ability to distinguish vaccinated animals from infected ones, durability of immunity and ease of administration.

Other essential characteristics include the safety, potency and efficacy of the vaccines. Although some vaccine companies have received approval to start large-scale production, the use of these vaccines is still a sensitive issue, mainly because of the international trade implications. Indeed, authorising the use of these vaccines could negatively affect the global poultry trade, further complicating the management of the health crisis.

Meanwhile, scientists continue to gather important information on the behaviour and evolution of the H5N1 virus, with the aim of better understanding its mechanisms of spread and its potential mutations that could make it even more dangerous. A recent study by a team of researchers from the University of Texas Medical Branch at Galveston compared two strains of H5N1, one isolated from cattle and the other from a wild bird in Mongolia in 2005.

The results, published in the journal Scientific Reports, highlighted worrying features in the bovine strain, which showed more efficient replication in human lung cells and faster growth than the older strain. Furthermore, in experiments conducted on mice, the bovine strain showed greater pathogenicity, leading to a rapid evolution of lung disease and higher levels of virus in the animals' brains. This caused a significant increase in mortality in mice exposed to the virus through different routes of infection. The authors of the study pointed out that the results suggest that this strain of H5N1 could exploit innate immune escape mechanisms, which increases concerns about the evolutionary potential of the virus and its ability to adapt to new hosts, including humans.

In parallel, another study conducted by St. Jude Children's Research Hospital addressed the issue of antiviral therapy against the H5N1 virus. Using a mouse model, the researchers tested the efficacy of two FDA-approved antiviral drugs: oseltamivir and baloxavir, administered after mice had been exposed to a lethal dose of H5N1-infected milk.

The results, published in the journal Nature Microbiology, showed that baloxavir treatment had significantly better effects than oseltamivir. This drug improved survival rates and reduced the spread of the virus, suggesting that baloxavir might be a more effective therapy for treating severe H5N1 infections. Consequently, the researchers proposed that baloxavir, in combination with other neuraminidase inhibitors, should be considered in drug stocks prepared for future influenza pandemics.

Overall, these developments show how scientific research is making significant progress in understanding and controlling avian influenza. From the creation of new vaccines and antiviral treatments to the continued analysis of virus strains, scientists are laying the foundations for a more rapid and effective response to avian influenza threats, helping to improve global health security.

However, continuous monitoring of the spread of the virus and its changes remains essential. The analysis of epidemiological and genomic data is now crucial to understanding the evolution of the virus. Our research group GABIE (Genomics, Artificial intelligence, Bioinformatics, Infectious diseases and Epidemiology) is strongly committed to studying the trend and identifying significant mutations, including through the creation of open-access databases that can be used by researchers around the world, allowing real-time data sharing.

Avian influenza is a warning about the complex interconnection between ecosystems, animals and human health. Its gradual adaptation to mammalian hosts and increasing geographical spread demand a broader reflection on how we manage emerging infectious diseases. The biggest mistake we could make would be to consider the virus a problem confined to the animal world.

Pandemics do not come from nowhere, but mature over time, fuelled by ecological, economic and social factors. The case of H5N1 reminds us that zoonotic diseases are not isolated events, but phenomena linked to global dynamics involving deforestation, wildlife trade, intensive food production and climate change. The traditional approach, which clearly separates human health from animal and environmental health, has proven inadequate. This is where the One Health paradigm becomes crucial: health is a single, indivisible concept, linking the well-being of human beings to that of the ecosystems and animals with which we share the planet.

Adopting a One Health strategy means moving beyond the emergency logic, which intervenes only when a crisis is declared, to a prevention model based on surveillance, interdisciplinary cooperation and risk management policies. This implies investing in research, strengthening zoonoses monitoring systems, stricter regulation of intensive farming and live animal markets and rethinking our relationship with the environment.

H5N1, like other emerging viruses, feeds on vulnerabilities in our global system, exploiting gaps in biosecurity measures and interconnections between continents to spread. The lesson of the COVID-19 pandemic should have taught us that waiting to act when a virus has already made the species leap can be devastating.

The scientific community has already sounded the alarm, calling for more attention and resources to contain the H5N1 threat before it is too late. Interdisciplinary collaboration is essential to develop effective and, above all, lasting strategies. However, this is not just a technical issue: a change of perspective is needed in global health governance, which recognises the urgency of protecting biodiversity and reducing anthropogenic pressures on ecosystems.

In a deeply interconnected world, the idea that a highly pathogenic virus can remain confined to a single species or geographical area is a dangerous misunderstanding of reality. H5N1 continues its evolution, and how we deal with this threat will determine its future impact. We cannot afford to view avian influenza as just a livestock or veterinary problem: it is an indicator of the fragilities of our global health system and our relationship with the environment. The time to act is now, before the virus takes the next step in its evolutionary race, turning a silent emergency into a crisis with no return.

* Unit of Medical Statistics and Molecular Epidemiology, University Campus Bio-Medico of Rome (Adjunct professor/Research Fellow Faculty of Medicine)