Avian Influenza (Bird Flu) Types and Subtypes

Introduction

Bird flu, also known as avian influenza, is a viral infection that primarily affects birds but can occasionally spread to humans and other mammals. These viruses are categorized based on two surface proteins: hemagglutinin (H) and neuraminidase (N). To date, 16 hemagglutinin (H1 to H16) and 9 neuraminidase (N1 to N9) subtypes have been identified. As of December 2024, the ongoing global outbreak of bird flu has raised significant concerns due to its widespread nature and potential impact on various species.

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Since 2003, the global tally of human bird flu cases stands at approximately 900, with about half of these individuals succumbing to the disease, according to data from the World Health Organization. This suggests a case fatality rate of 50%, indicating extreme lethality. However, experts believe this percentage might be misleading. The reason is that severe cases are more frequently reported than mild ones, which means less severe infections likely aren't included in these statistics. The 4 strains of avian influenza that have caused concern in recent years are:

• H5N1 (since 1997)
• H7N9 (since 2013)
• H5N6 (since 2014)
• H5N8 (since 2016)

Low Pathogenic and Highly Pathogenic Avian Influenza A Viruses

Low Pathogenic Avian Influenza (LPAI)

Low Pathogenic Avian Influenza viruses typically cause mild symptoms in birds and pose minimal risk to human health. Low pathogenic avian influenza (LPAI) viruses typically result in mild or no symptoms in infected birds. In chickens and other poultry, LPAI may cause subtle signs such as ruffled feathers or a decrease in egg production. Wild birds infected with LPAI viruses often show no signs of illness at all. However, it's important to note that some LPAI viruses have the potential to mutate into highly pathogenic strains, particularly when circulating in poultry populations. This mutation can lead to more severe disease and higher mortality rates in affected birds.

Highly Pathogenic Avian Influenza (HPAI)

These strains can lead to severe disease and high mortality rates in birds. Certain HPAI viruses have caused sporadic human infections, often resulting in serious illness. Highly pathogenic avian influenza (HPAI) viruses are a subset of avian influenza A viruses, specifically some A(H5) and A(H7) strains, that cause severe illness and high mortality in infected poultry. These viruses differ from the more common low pathogenic avian influenza (LPAI) A viruses, which include most A(H5) and A(H7) strains circulating among birds.

HPAI A(H5) or A(H7) infections can be devastating for poultry, affecting multiple internal organs and potentially causing up to 90-100% mortality in chickens, often within just 48 hours. Interestingly, ducks may carry these viruses without showing any signs of illness.

The impact of HPAI extends beyond domesticated poultry. These viruses can spill back into wild bird populations, leading to further geographic spread as infected birds migrate. While some wild bird species may carry HPAI A(H5) or A(H7) subtypes asymptomatically, other subtypes can cause severe disease and mortality in both wild birds and poultry.

This complex interplay between HPAI viruses, poultry, and wild birds highlights the importance of comprehensive surveillance and control measures in both domestic and wild avian populations.

Types and Strains

The main virus involved in the current global outbreak is classified as H5N1 clade 2.3.4.4b. However, genetic diversification has led to the emergence of other strains and subtypes. As of December 2024, this strain continues to be a significant concern due to its high pathogenicity and ability to infect a wide range of species.

H5N1

H5N1 remains the predominant subtype detected in both domestic and wild birds. It is highly pathogenic and has been responsible for numerous outbreaks across different continents. The virus has shown an ability to infect a wide range of species, including birds, mammals, and humans.

As of May 3, 2024, there were 889 human cases of H5N1 with 463 deaths reported in 23 countries since 2003. As of December 2024, H5N1 remains the primary concern. Other strains like H5N6 and H9N2 continue to cause sporadic human infections, particularly in Asia

H5N2

On November 8, 2024, the Canadian Food Inspection Agency (CFIA) confirmed the presence of the H5N2 subtype in poultry in British Columbia. This marks the first detection of this subtype in Canada. The H5N2 subtype shares the same H gene as H5N1, indicating that it is also highly pathogenic.

Other Subtypes

While H5N1 and H5N2 are currently the most prominent, other subtypes have been observed in recent years.

H5N6

These viruses with the H5-2.3.4.4b hemagglutinin (HA) gene became prominent globally in 2018-2020. Since its detection, H5N6 has led to infections in birds and humans, primarily in Asia, with a number of human cases resulting in severe disease.

H5N1 clade 2.3.4.4b viruses represent a significant evolution in avian influenza viruses. Their rapid geographic spread, increased genetic reassortment, enhanced mammalian adaptation, and high pathogenicity set them apart from previous H5N1 strains. These characteristics underscore the need for continued vigilance and research to mitigate the potential risks posed by these viruses to both animal and human health.

Infected birds shed the virus in their saliva, mucus, and feces. The virus was first detected in poultry in 2013, since then spreading among wild bird populations and poultry around the world. Humans can be infected through unprotected contact with infected birds or contaminated surfaces.

H5N8

H5N8 is a subtype of the influenza A virus and is highly lethal to wild birds and poultry.

This strain has caused significant poultry outbreaks in Europe and Asia, with occasional spillover into wild birds. It's also been noted for its ability to reassort with other strains, potentially creating new variants. Its intravenous pathogenicity index (IVPI) is greater than 1.2, giving it a mortality rate of at least 75 percent.

On 20 February 2021, Russia reported the first known cases of H5N8 in humans. Seven people were confirmed to have been infected at a farm in southern Russia where outbreaks had been reported.

Anna Popova, head of Rospotrebnadzor, in an interview published in The Moscow Times on 12 March 2021, warned that there was a "high degree of probability" of human-to-human transmission of H5N8.

H7N3

Influenza A virus subtype H7N3 (A/H7N3) is a subtype of the species Influenza A virus (sometimes called bird flu virus).

Recently detected in Victoria, Australia, this strain is common there but less pathogenic compared to H5N1. It led to the culling of hundreds of thousands of chickens in an egg farm due to rapid spread and high mortality in birds.

H7N9

Emerging in 2013, H7N9 has infected both birds and humans, particularly in China, where it has caused human infections with a high mortality rate in some outbreaks.

H9N2

Recent research has revealed that H9N2 avian influenza virus serves as a gene donor for other influenza viruses that have infected humans, including H7N9 and H10N8. The H9N2 virus provides internal genes to these emerging viruses, potentially enhancing their ability to infect humans. H9N2 viruses frequently reassort with other avian influenza virus subtypes, leading to the emergence of novel strains.

H9N2 is constantly evolving, acquiring new genetic traits that can enhance its ability to infect different species. This genetic flexibility allows it to jump the species barrier, potentially leading to zoonotic infections.

H9N2 infections in humans typically cause mild symptoms. However, when H9N2 internal genes combine with other virus subtypes, the resulting reassortant viruses can pose a more significant threat to human health. The ability of H9N2 to donate genes to other influenza viruses has raised concerns about its potential role in a future influenza pandemic.

Genetic Evolution and Reassortment

The bird flu virus has demonstrated a significant capacity for genetic evolution and reassortment. In 2020, reassortment between H5-2.3.4.4b viruses and other avian influenza strains led to the emergence of a new H5N1 strain. As the virus spreads globally, it continues to swap genes with local flu viruses, potentially leading to new variants.

Recent mutations in some Eurasian/North American reassortant H5N1 strains have shown enhanced polymerase activity, improved replication in mammalian cells, and increased virulence in mice.

Transmission and Spread

The current outbreak has seen bird flu spread to various species and regions:

• Birds: Wild and domestic birds remain the primary carriers and victims of the virus.
• Mammals: Increasing reports of infections in mammals, including cows, goats, cats, and alpacas, have raised concerns about potential mammal-to-mammal transmission.
• Humans: While rare, human infections have occurred, primarily through direct contact with infected animals or contaminated environments.

Preventive Measures and Surveillance

• Surveillance: Continuous monitoring in both wild and domestic birds is crucial. This includes testing of birds, both live and dead, to detect and contain outbreaks early.
• Biosecurity: Enhanced biosecurity measures in poultry farms are vital to prevent the introduction and spread of the virus. This includes controlling movement of birds and people, and maintaining hygiene.
• Public Health: For humans, avoiding direct contact with sick or dead birds, wearing protective gear when handling poultry, and ensuring proper cooking of poultry products are recommended. Vaccines for humans against specific strains like H5N1 are under development but not widely available.

Recent Developments

In late 2024, mutations in the H5N1 virus have been detected, raising concerns about its potential to spread more easily among humans. On December 18, 2024, the CDC confirmed the first severe case of H5N1 bird flu in the United States, involving a patient hospitalized in Louisiana. This case is significant as it marks the first instance of severe illness linked to the virus in the U.S. In the United States and involved mutations in the hemagglutinin (HA) gene, which may facilitate transmission through respiratory droplets. Similarly, a severe case in Canada exhibited comparable mutations. These genetic changes were not present in samples from infected birds, suggesting they developed after human infection. Additionally, the virus has been detected in mammals, including dairy cows in the United States, indicating an expanding host range. This development underscores the importance of monitoring and preparedness to prevent potential human-to-human transmission.

As of December 2024, cases have been reported from every continent. The virus has even reached Antarctica, raising fears of potential catastrophic impacts on previously unexposed animal populations. Researchers have so far documented H5N1 infections at a number of seabird colonies on or near Antarctica. Researchers fear birds will ultimately spread the deadly virus across the southern continent and carry it to Australia. By December 2024, over 800 dairy cattle farms in 16 U.S. states were affected by HPAI virus

January 16, 2025, 10:00 AM ET (U.S. CDC)

A panzootic of highly pathogenic avian influenza A(H5N1) viruses is currently affecting wild birds. In the United States, there have been outbreaks with these viruses among poultry and dairy cows, as well as infections among other animals. The U.S. Centers for Disease Control and Prevention (CDC) is issuing this Health Alert Network (HAN) Health Advisory to clinicians and laboratories due to sporadic human infections with avian influenza A(H5N1) viruses amid high levels of seasonal influenza activity. CDC is recommending a shortened timeline for subtyping all influenza A specimens among hospitalized patients and increasing efforts at clinical laboratories to identify non-seasonal influenza. Clinicians and laboratorians are reminded to test for influenza in patients with suspected influenza and, going forward, to now expedite the subtyping of influenza A-positive specimens from hospitalized patients, particularly those in an intensive care unit (ICU). This approach can help prevent delays in identifying human infections with avian influenza A(H5N1) viruses, supporting optimal patient care and timely infection control and case investigation.

Editorial Insights, Analysis, and Developments

The current types and strains of bird flu, notably the H5N1 clade 2.3.4.4b, pose significant challenges due to their high pathogenicity and ability to infect multiple species while rapidly evolving. Although there's no evidence of sustained human-to-human transmission, the continuous evolution of these viruses, including subtypes like H7 and H9, demands vigilant surveillance and research. This is crucial for managing the threat across different populations and regions, safeguarding both public health and poultry/wildlife. The interconnectedness of animal and human health highlights the necessity for a One Health approach, integrating efforts from veterinary, human health, and environmental sectors to effectively control and mitigate the spread of avian influenza, emphasizing the need for awareness, preparedness, and global cooperation - Disabled World (DW).