Influenza A Viruses

Influenza A viruses are further classified according to surface proteins, haemagglutinin (H) and neuraminidase (N). There are 18 haemagglutinin and 11 neuraminidase subtypes defined. The composition of H and N subtypes defines subtypes of influenza, such as current annual influenza viruses, A(H1N1) or A(H3N2). The H and N proteins of influenza viruses almost continuously slightly change in line with their spread, and therefore the composition of influenza vaccines must be constantly reviewed in order for them to remain effective. These minor changes can lead to varying severity of annual influenza outbreaks, but the H and N markings do not change with them (strain evolves but an actual new strain does not develop).

Historically, pandemics are triggered when a new strain of influenza A virus emerges. A new H+N combination has then usually emerged due to rearrangement. Recombination involves the mixing of genetic material from two viruses: e.g. infection of H5N1 and H3N2 in the same animal (usually birds) at the same time can lead to the emergence of e.g. an H5N2 strain that no animal has previously been infected with and therefore resistance to the spread of the new virus is minimal. In order for a new strain to be transmitted between humans, mutations in H and/or N usually also need to occur, which leads to the adaptation of the new strain to mammals and then a virus has emerged that can be transmitted between humans. A lack of immunity in the society to such new strains can then lead to a widespread spread and a serious epidemic. Influenza A pandemics that we know are:

• 1918 (H1N1): The Spanish flu, which caused millions of deaths worldwide.

• 1957 (H2N2): The Asian flu, which replaced H1N1 until 1968.

• 1968 (H3N2): The Hong Kong flu, which has since persisted alongside H1N1.

• 2009 (H1N1): The swine flu, a rearranged strain of the original H1N1 virus.

Influenza strains adapted to other animals can infect humans. Influenza transmission from animals to humans happens regularly and is considered zoonosis (diseases that are transmitted from animals to humans), but rarely do such infections lead to a pandemic. In order for infections to be easily transmitted between humans and lead to an epidemic, a series of "unfortunate" mutations are needed to adapt to humans or recombination with a better adapted virus.

Avian Influenza

Avian influenza viruses primarily infect birds, but can be transmitted to mammals, including humans. Infections in humans are most common in Southeast Asia, where proximity between humans and birds is common.

Avian influenza is further divided into two categories:

• Low pathogenic avian influenza (LPAI): Asymptomatic or causes mild disease in birds. Low viral load, spreads between birds in the close vicinity but minimally outwards.

• Highly pathogenic avian influenza ( HPAI): Can spread widely and cause serious illness in birds and possibly other animals. A large amount of virus is found in droppings and on the feathers of sick birds.

In 2021, a new variant of HPAI virus H5N1, called H5N1 cluster 2.3.4.4b, began to spread worldwide among wild birds. This strain has led to:

• Massive outbreaks in poultry and wild birds.

• Frequent spillovers to mammals such as mink, foxes, seals and sea lions, as well as cats and mice. Most mammals infected have been in contact with sick birds or in an environment contaminated with bird droppings. However, infections have probably also spread between animals.

• Sporadic human infections, often linked to direct contact with infected birds or their environments.

From September to December 2024, HPAI H5N5 outbreaks have been reported in northern Europe, including in poultry and wild birds in Iceland, the UK, the Faroe Islands and Norway, elsewhere only in wild birds.

Pets and Farm Animals

Birds such as chickens that roam outdoors and are in close contact with wild birds or the droppings of wild birds are easily infected with H5N1 and H5N5. Most infections to humans from animals have been from birds. Felines, including domestic cats and large cats, have become ill with H5N1 associated with the spread in birds. There has been a spread in dairy cows in the United States and infections in cats there have also been linked to unpasteurized milk (see later). Infection often leads to the death of cats. No transmission from felines to humans has been observed. Dogs can also become infected with H5N1 if they come into close contact with infected birds.

Human Infections

Human cases of avian influenza often result from close contact with infected birds, their waste, or contaminated environments. Transmission occurs through:

• Handling of live or dead birds.

• Cleaning contaminated areas.

• Exposure to airborne particles from feathers, feces, or other bird-derived materials.

There is no risk of infection when consuming well-cooked eggs or meat, as the virus is killed by heating. Proper washing kills influenza virus.

Symptoms in people who have been diagnosed with avian influenza have ranged from none or mild to severe leading to death. Asymptomatic infections can be found during screening of risk groups and are signs that the virus is contaminating the environment and is only transmitted to the eyes or mucous membranes from which a sample is taken, without causing infection. Mild symptoms often resemble typical flu symptoms, such as fever, cough, or conjunctivitis. Aerosol or airborne virus particles can travel deep into the respiratory tract and then potentially cause illness, possibly serious, such as viral pneumonia or encephalitis.

Iceland and Europe

Since 2021, avian influenza A(H5N1) has spread significantly across Europe and globally in millions of birds, primarily wild waterfowl, seabirds and poultry. Infections of mammals have also been reported. In Iceland, avian influenza A(H5N1) was first detected in wild birds in April 2022 and later the same year in a group of domestic chickens in one location.

In the autumn of 2023, avian influenza A(H5N5) was detected for the first time in wild birds in Iceland and then again in September 2024. In December 2024, a poultry outbreak of H5N5 was reported in a commercial turkey farm in Iceland. Subsequently, in January 2025, at least two domestic cats in different regions in Iceland were confirmed to have contracted H5N5 bird flu, with other cats likely having died from the same strain. These are the first mammals diagnosed with HPAI in Iceland and the first cases of H5N5 in pets reported to the World Organization for Animal Health (WOAH). A large number of sick and dead migratory birds have been found at present, mainly in the capital area, and H5N5 avian influenza has been confirmed in swans and geese.

Although significant exposure has been present in the EU/EEA area in recent years, especially due to A(H5) poultry outbreaks, there have been no reports of confirmed infections in humans. Spain reported two A(H5N1) cases in 2022 and the United Kingdom one in 2021, but the diagnoses were unrelated to illness and attributed to contamination during the slaughter of sick animals and the cleaning of animal farms after slaughter.

North America

In March 2024, HPAI H5N1 genotype B3.13 was detected in dairy cows in the United States and the infection has spread to a number of cow farms. The spread of H5N1 in dairy cows is primarily due to milking equipment and the transport of cattle between states. Cows are also believed to have infected other animals, including humans. Infected cows primarily show a decrease in milk production, unlike poultry, where illness and rapid death is more obvious. Genotypes B3.13 and D1.1 (below) have not been found in Europe.

At the time of writing, the US Centers for Disease Control and Prevention (CDC) has recorded 74 confirmed or probable infections in humans. Most of the cases are related to direct exposure to sick dairy cows (44 people) or poultry (23 people). No human-to-human transmission has been observed. Most human cases associated with the circulating genotype in dairy cows have been mild.

Two serious infections in North America have been linked to different a D1.1 genotype carried by wild migratory birds: one resulted in the death of an individual, who was over 65 years of age, with underlying diseases who had exposure to sick and dead birds in their backyard. The other infection was in an adolescent who is now recovering after prolonged intensive care treatment.

Vaccinations and Prevention of Occupational Risk of Infection

The risk of a large-scale outbreak caused by the new influenza A virus exists due to the possible recombination between avian influenza virus and viruses adapted to humans or other mammals. Preventing co-infections of different influenza viruses in mammals, including humans, is key to reducing the risk of recombination and pandemics.

Vaccination against annual influenza has been recommended for people at occupational risk of avian influenza from autumn 2023 in Iceland, to reduce the risk of co-transmission of human and avian influenza viruses in those circumstances. However, standard vaccination against annual influenza does not provide protection against avian influenza and therefore recommendations and rules on infection prevention must be followed where there is a risk of transmission of avian influenza.

A specific vaccine against avian influenza A(H5) was recently approved by the European Medicines Agency (EMA). The target groups for vaccination are first and foremost individuals who are exposed to animals, their waste or a polluted environment in their work. Considering that recent infections of A(H5N1) among occupationally exposed groups have been mild and there have been no human infections in the EU/EEA so far, recommendations for general vaccinations are not considered necessary at this point. In Finland, workers at increased risk have been offered vaccination. Increased spread in mammals, an increase in serious illness in people or confirmed transmission between humans, here or abroad, would give rise to vaccinations of people at occupational risk in Iceland.

Preventive measures include:

• Thorough hand hygiene (with hand washing and hand sanitizer).

• Avoiding direct contact with infected birds or their environment.

• Use of protective equipment during handling animals or cleanup where sick animals or carcasses have been: Face masks (viral masks), eye protection and impermeable protective clothing.

• Implementation of biosecurity measures on farms according to relevant guidelines. Good ventilation, proper cleaning, pest control, etc. reduce the spread of influenza viruses.

Although the risk of infection and especially illness is low, individuals who are exposed to avian influenza (e.g. due to direct contact with infected animals or carcasses of animals that have died from avian influenza) should monitor their symptoms for 14 days. If symptoms occur (e.g. fever >38 °C, cough, shortness of breath), the nearest health care centre should be contacted for immediate testing.

Public Precautions

General hygiene and cleaning are most important. This includes regular hand washing with soap and water or using alcohol-based hand sanitizer, especially after handling birds or contaminated surfaces. Safe handling of poultry and wild animals should also be emphasized, such as wearing gloves, avoiding touching one's face and washing hands, and cleaning contaminated surfaces thoroughly. People who keep birds, including domestic chickens, need to consider more specific protection against infection to household members if the birds become ill, according to guidelines. Consumption of unpasteurized milk is cautioned.

The public should also minimize exposure by, among other things:

• stay away from sick or dead wild birds and animals, and

• limit the contact of domestic animals and pets with wild animals when infections are widespread.

Preparedness for the Influenza Pandemic

The most effective measure against pandemics is a robust system of monitoring to identify threats before they take hold in communities and a preparedness and response plan if a threat emerges.

Zoonosis are occurring with increasing frequency since the mid-20th century, especially where the proximity of wild animals with domestic animals and people is close. Wet markets, which sell fresh produce along with wild mammals and birds, are high-risk areas for such diseases. When a new respiratory virus begins to spread from person to person, we will unlikely be able to halt the spread.

Currently, the global capacity to produce influenza vaccines is about 6.8 billion doses per year. So far, no influenza vaccines are produced without cultivating the virus in large quantities. Therefore, a vaccine would not be available for at least six months after a new virus spreads sufficiently to be considered a pandemic threat. Vaccines against novel influenza viruses often need to be given in two doses to get adequate protection. Therefore, vaccine development capacity must be increased and production processes accelerated, e.g. through the use of mRNA technology, in order to strengthen the response to the next influenza pandemic.

Vaccines do not completely prevent infections, but they significantly reduce the risk of severe illness. For individuals at the highest risk of serious complications, the prophylactic use of antiviral drugs may be necessary. These drugs can also be used to treat those already at risk of severe illness or to lower the likelihood of infection. Ensuring widespread access to these medications is critical for those who may need them. Additionally, when vaccine supplies are limited, prioritization strategies should consider factors such as access to effective treatments.

Influenza progresses more rapidly than many other viral infections. Symptoms typically appear within 1–2 days after exposure, with the highest risk of transmission occurring during the first 2–3 days of illness. Although the acute phase of influenza may pass quickly, complications such as bacterial infections are common and can significantly prolong illness. Reducing the spread of influenza during a pandemic is crucial, as complications-like sepsis caused by streptococcal infections-can result in high mortality rates. Containing the virus until vaccination can effectively suppress its spread can save many lives.

Community-based measures proven effective during the COVID-19 pandemic can also play a significant role on an individual level in mitigating the impact of influenza pandemics and annual epidemics. These include:

• Practicing proper hand hygiene and observing cough and sneeze etiquette,

• Staying at home and avoiding travel when symptomatic, and

• Minimizing contact with vulnerable groups, such as immunocompromised individuals, when illness is present at home or in the workplace.

The Chief Epidemiologist