Avian influenza (H5N1)

Avian influenza, known informally as avian flu, is a bird flu caused by the influenza A virus, which can infect people.

Influenza A virus subtype H5N1 (A/H5N1) is a subtype of the influenza A virus which can cause illness in humans and many other species.

It is similar to other types of animal flu in that it is caused by a virus strain that has adapted to a specific host. 

Influenza A virus subtype H5N1, commonly known as avian influenza or bird flu, is a highly pathogenic strain of the influenza A virus. 

The H in H5N1 stands for hemagglutinin.

N1 stands for the first of several known types of the protein neuraminidase.

It is maintained in many bird populations, especially in Southeast Asia. 

Though influenza A is adapted to birds, it can also stably adapt and sustain person-to-person transmission.

It primarily affects birds, particularly poultry, but can also infect humans and other mammals. 

Avian pathogenicity is gradually continuing to rise in endemic areas, but the avian influenza disease situation in farmed birds is being held in check by vaccination.

There is no evidence of sustained human-to-human transmission of the virus.

HPAI A(H5N1) is epizootic (an epidemic in nonhumans) and panzootic (affecting animals of many species, especially over a wide area), killing tens of millions of birds and spurring the culling of hundreds of millions of others to stem its spread.

H5N1 is a zoonotic virus, meaning it can be transmitted from animals to humans.

A bird-adapted strain of H5N1, called HPAI A(H5N1) for highly pathogenic avian influenza virus of type A of subtype H5N1.

The genes of the Spanish flu virus shows it to have genes adapted from both human and avian strains.

As of May 2020, the WHO reported a total of 861 confirmed human cases which resulted in the deaths of 455 people since 2003.

Several H5N1 vaccines have been developed and approved, and stockpiled.

HPAI A(H5N1) is considered an avian disease, although there is some evidence of limited human-to-human transmission of the virus.

A risk factor for contracting the virus is handling of infected poultry.

Transmission of the virus from infected birds to humans has been characterized as inefficient.

Around 60% of humans known to have been infected with the Asian strain of HPAI A(H5N1) have died from it.

H5N1 may mutate/reassort into a strain capable of efficient human-to-human transmission. 

H5N1 virus is regarded to be the world’s largest pandemic threat.

H5N1 may cause more than one influenza pandemic, as it is expected to continue mutating in birds.

The symptoms are similar to those of regular influenza, including fever, cough, sore throat, and muscle aches. 

H5N1 infections tend to progress rapidly and can cause severe respiratory distress, pneumonia, and multiple organ failure.

Preventive measures: maintaining good personal hygiene, avoiding contact with sick birds or their droppings, and properly cooking poultry products, can help reduce the risk of H5N1 transmission to humans. 

Vaccines have been developed for H5N1, but their availability is limited. 

Antiviral medications may be used to treat infected individuals.

Monitoring H5N1 outbreaks due to the potential for the virus to mutate and become more easily transmissible among humans. 

Genetic analysis of the H5N1 virus shows that influenza pandemics from its genetic offspring can easily be far more lethal than the Spanish flu pandemic.

The different sites of infection of seasonal H1N1 versus avian H5N1 influences their lethality and ability to spread.

H5N1 has caused several outbreaks in birds across different parts of the world, with significant economic consequences for the poultry industry. 

The virus is primarily transmitted through contact with infected birds or their bodily fluids, such as saliva, nasal secretions, or feces. 

Human-to-human transmission is rare but possible in certain circumstances.

Humans infection with H5N1 can lead to severe respiratory illness, with a high mortality rate. 

H5N1 outbreaks could lead to a global pandemic with significant public health implications.

The severity of the H5N1 infection depends in large part on the state of the infected persons’ immune systems and whether they had been exposed to the strain before.

When the H5N1 strain infects humans, it will replicate in the lower respiratory tract, and consequently will cause viral pneumonia.

  1. There is as yet no human form of H5N1.

Pigs can also be infected with human, avian, and swine influenza viruses, allowing for mixtures of genes to create a new virus, which can cause an antigenic shift to a new influenza A virus subtype which most people have little to no immune protection against.

Avian influenza strains are divided into two types based on their pathogenicity: high pathogenicity (HP) or low pathogenicity (LP).

The most well-known HPAI strain, is H5N1.

Companion birds in captivity are unlikely to contract the virus and there has been no report of a companion bird with avian influenza since 2003. 

Pigeons can contract avian strains, but rarely become ill and are incapable of transmitting the virus efficiently to humans or other animals.

Avian or bird flu is caused by viruses adapted to birds.

Outbreaks have become more common due to the high density and frequent movement of flocks from intensive poultry production.

From 2014 through 2015, United States poultry and egg producers experienced the largest outbreak of H5N2 in recorded history with approximately 51 million birds depopulated to control the spread of the disease. 

Since early 2022, more than 60 million birds in 47 states have died either directly from a bird flu virus infection or been culled as a result of possible exposure to infected birds.

The virus has been detected in ducks, geese, gulls,pelicans, swans, vultures, crows, owls, eagles, and many other species of wild birds.

The list of mammals with confirmed infections in Europe and the Americas includes: badger, Blackbeard, bobcat, coyote, dolphin, ferret, fishercat, fox, leopard, lynx, opposum, otter, pig, polecat, porpoise, raccoon, dog, and skunk.

Mammals probably become infected with H5N1 while eating sick or dead birds with high virus loads.

The type with the greatest risk is highly pathogenic avian influenza (HPAI).

Caused by H5N1 stain of influenza A which is endemic in birds in large parts of Asia.

In the last 20 years, fewer than 900 confirmed human cases of H5N1 have been reported.

Avian influenza, doesn’t easily spread between people and other mammals.

Human infections have generally been dead end infections.

Strikes primarily children and young adults and is associated with a high mortality rate.

Evidence for bird-to-human transmission, possibly environment-to-human and nonsustained human-to-human transmission have been seen.

Genetic factors distinguish between human flu viruses and avian flu viruses include:

PB2 (RNA polymerase)

HA (hemagglutinin)

Out of the three types of influenza viruses (A, B, and C), influenza A virus can cause zoonotic infections, with a natural reservoir almost entirely in birds.

There are many subtypes of avian influenza viruses, but only some strains of five subtypes have been known to infect humans: H5N1, H7N3, H7N7, H7N9, and H9N2.

Most human cases of the avian flu are a result of either handling dead infected birds or from contact with infected fluids. 

It can also be spread through contaminated surfaces and droppings. 

While most wild birds have only a mild form of the H5N1 strain, once domesticated birds such as chickens or turkeys are infected, H5N1 can potentially become much more deadly because the birds are often in close contact. 

H5N1 is a large threat in Asia-low hygiene conditions and close quarters. 

Although it is easy for humans to contract the infection from birds, human-to-human transmission is more difficult without prolonged contact. 

Strains of avian flu may mutate to become easily transmissible between humans.

As of November 29, 2006 258 human cases have occurred with human transmission not going beyond one person.

Has resulted in the death or destruction of more than 140 million birds at a cost of more than 10 billion dollars.

Viruses have the potential to cause severe respiratory illness with 369 human cases and 234 deaths as of 2008.

Spreading of H5N1 from Asia to Europe is much more likely caused by poultry trades than dispersing through wild bird migrations, being that in recent studies, there were no secondary rises in infection in Asia when wild birds migrate south again from their breeding grounds. 

Infection patterns followed transportation such as railroads, roads, and country borders, suggesting poultry trade as being much more likely. 

Strains of avian flu  that have existed in the United States, have been extinguished and have not been known to infect humans.

Birds that have been put down because of avian influenza. 

The virus is spread by contact between healthy and unhealthy birds.

Avian influenza is most often spread by contact between infected and healthy birds, though can also be spread indirectly through contaminated equipment.

The virus is found in secretions from the nostrils, mouth, and eyes of infected birds as well as their droppings. 

HPAI (high pathogenic avian) infection is spread to people often through direct contact with infected poultry, such as during slaughter or plucking.

Though the virus can spread through airborne secretions, the disease itself is not an airborne disease. 

Highly pathogenic strains spread quickly among flocks and can destroy a flock within 28 hours; the less pathogenic strains may affect egg production but are much less deadly.

Humans can contract the avian influenza virus from birds, but human-to-human contact is much more difficult without prolonged contact. 

However strains of avian flu may mutate to become easily transmissible between humans.

Some strains of avian influenza are present in the intestinal tract of large numbers of shore birds and water birds, but rarely cause human infection.

Man made ecosystems contribute to modern avian influenza virus ecology: 

integrated indoor commercial poultry, 

range-raised commercial poultry, 

live poultry markets, 

backyard and hobby flocks, 

bird collection and trading systems including cockfighting. 

Indoor commercial poultry has had the largest impact on the spread of HPAI.

The highly pathogenic influenza A virus subtype H5N1 is an emerging avian influenza virus that is causing global concern as a potential pandemic threat. 

H5N1 has killed millions of poultry in a growing number of countries throughout Asia, Europe, and Africa. 

The  coexistence of human flu viruses and avian flu viruses, especially H5N1, may provide an opportunity for genetic material to be exchanged between species-specific viruses, possibly creating a new virulent influenza strain that is easily transmissible and lethal to humans. 

The mortality rate for humans with H5N1 is 60%.

Levels of cytokines in humans infected by the H5N1 flu virus are elevated, particularly tumor necrosis factor-alpha, a protein associated with tissue destruction at sites of infection and increased production of other cytokines. 

Flu virus-induced increases in the level of cytokines is also associated with flu symptoms, including fever, chills, vomiting and headache. 

Tissue damage associated with pathogenic flu virus infection can ultimately result in death.

The inflammatory cascade triggers a ‘cytokine storm, a positive feedback process of damage to the body resulting from immune system stimulation. 

H5N1 induces higher levels of cytokines than the more common flu virus types.

The first human H5N1 outbreak occurred in 1997, there has been an increasing number of HPAI H5N1 bird-to-human transmissions, leading to clinically severe and fatal human infections. 

Because a significant species barrier exists between birds and humans, the virus does not easily spread to humans. 

Although millions of birds have become infected with the virus since its discovery, very few people have died from H5N1.

Culling is used in order to decrease the threat of avian influenza transmission by killing potentially infected birds. 

Culling results in severe economic impacts especially for small scale farmers, and culling may be an ineffective preventative measure. 

In the short-term, mass culling achieves its goals of limiting the immediate spread of HPAI, but impedes the evolution of host resistance which is important for the long-term success of HPAI control. 

H5 subtype viruses contain hemagglutinin for which humans have limited immunity.

Viruses have the potential to cause severe respiratory illness with 169 human cases and 91 (54%) deaths s of Feb 13, 2006.

Clinical manifestations in humans range from asymptomatic infection or a mild upper respiratory tract illness to severe pneumonia and multiorgan failure.

Many viruses isolated from humans have been genotypically resistant to adamantanes and oseltamivir.

In birds signs of H5N1 in birds range from mild—decrease in egg production, nasal discharge, coughing and sneezing—to severe, including loss of coordination, energy, and appetite; soft-shelled or misshapen eggs; purple discoloration of the wattles, head, eyelids, combs, and hocks; and diarrhea. 

Sometimes the first noticeable sign of H5n1 is sudden death.

H5N1 has strains called highly pathogenic (HP) and low-pathogenic (LP). 

Avian influenza viruses that cause HPAI are highly virulent, and mortality rates in infected flocks often approach 100%. 

LPAI viruses have negligible virulence, but these viruses can serve as progenitors to HPAI viruses. 

The strain of H5N1 responsible for the deaths of birds across the world is an HPAI strain.

All other strains of H5N1, including a North American strain that causes no disease at all in any species, are LPAI strains. 

All HPAI strains identified to date have involved H5 and H7 subtypes.

Normally, a highly pathogenic avian virus is not highly pathogenic to either humans or nonpoultry birds.

H5N1 subtype is an RNA virus.

HA codes for hemagglutinin, an antigenic glycoprotein found on the surface of the influenza viruses and is responsible for binding the virus to the cell that is being infected. 

NA codes for neuraminidase, an antigenic glycosylated enzyme found on the surface of the influenza viruses, and it facilitates the release of progeny viruses from infected cells.

The hemagglutinin (HA) and neuraminidase (NA) RNA proteins are most medically relevant as targets for antiviral drugs and antibodies. 

HA and NA are also used as the basis for the naming of the different subtypes of influenza A viruses. 

Influenza A viruses are significant for their potential for disease and death in humans and other animals. 

Influenza A virus subtypes that have been confirmed in humans, in order of the number of known human pandemic deaths that they have caused, include:

H1N1, caused the 1918 flu pandemic (“Spanish flu”) and the 2009 flu pandemic (“swine flu”) and is causing seasonal human flu

H2N2, which caused “Asian flu”

H3N2, which caused “Hong Kong flu” and causes seasonal human flu

H5N1, (“bird flu”), which is noted for having a strain that has killed over half the humans known to have been infected by it, infecting and killing species that were never known to suffer from influenza viruses before, unstoppable even by culling all involved poultry.

H7N7, which has unusual zoonotic potential.

H1N2, which is endemic in humans and pigs and causes seasonal human flu.

H7N9, has lead to 70 deaths.

Low pathogenic avian influenza H5N1 commonly occurs in wild birds. 

In most cases, it causes minor sickness or no noticeable signs of disease in birds. 

It is not known to affect humans at all. 

It it is possible for it to be transmitted to poultry and in poultry mutate into a highly pathogenic strain.

Influenza viruses have a relatively high mutation rate that is characteristic of RNA viruses. 

A previously uncontagious strain may then be able to pass between humans, one of several possible paths to a pandemic.

Genetic mutations in the hemagglutinin gene that cause single amino acid substitutions can significantly alter the ability of viral hemagglutinin proteins to bind to receptors on the surface of host cells. 

Such mutations in avian H5N1 viruses can change virus strains from being inefficient at infecting human cells to being as efficient in causing human infections as more common human influenza virus types.

There are several H5N1 vaccines for several of the avian H5N1 varieties, but the continual mutation of H5N1 renders them of limited use.

There is no highly effective treatment for H5N1 flu, but oseltamivir can sometimes inhibit the influenza virus from spreading inside the user’s body. 

This drug has become a focus for some governments and organizations trying to prepare for a possible H5N1 pandemic, stockpiling of three millions of treatment courses of Tamiflu to be used in case of a flu pandemic.

It is unsure about Tamiflu’s real effectiveness. 

Animal and lab studies suggest that Relenza (zanamivir), which is in the same class of drugs as Tamiflu, may also be effective against H5N1. 

Tamiflu-resistant strains have also appeared in the EU, which remain sensitive to Relenza.

H5N1 is easily transmissible between birds, facilitating a potential global spread of H5N1. 

H5N1 can undergo mutation and reassortment, creating variations which can infect species not previously known to carry the virus, however, not all of these variant forms can infect humans. 

H5N1 as an avian virus preferentially binds to a type of galactose receptors that populate the avian respiratory tract from the nose to the lungs.

These galactose receptors are virtually absent in humans, occurring only in and around the alveoli, structures deep in the lungs where oxygen is passed to the blood. 

Therefore, the virus is not easily expelled by coughing and sneezing, the usual route of transmission.

H5N1 is mainly spread by domestic poultry, both through the movements of infected birds and poultry products and through the use of infected poultry manure as fertilizer or feed. 

Humans with H5N1 have typically caught it from chickens, which were in turn infected by other poultry or waterfowl. 

Migrating waterfowl (wild ducks, geese and swans) carry H5N1, often without becoming sick.

Many species of birds and mammals can be infected with HPAI A(H5N1).

The role of animals other than poultry and waterfowl as disease-spreading hosts is unknown.

H5N1 may be spread indirectly, sticking  to surfaces or it gets kicked up in fertilizer dust to infect people.

H5N1 has mutated into a variety of strains with differing pathogenic profiles.

Some mutations are pathogenic to one species but not others, and some pathogenic to multiple species. 

Through antigenic drift, H5N1 has mutated into dozens of highly pathogenic varieties that belong to genotype Z of avian influenza virus H5N1, now the dominant genotype.

H5N1 isolates found in Hong Kong in 1997 and 2001 were not consistently transmitted efficiently among birds and did not cause significant disease in these animals. In 2002, new isolates of H5N1 were appearing within the bird population of Hong Kong. These new isolates caused acute disease, including severe neurological dysfunction and death in ducks. This was the first reported case of lethal influenza virus infection in wild aquatic birds since 1961.[63]

Mutations occurring within this genotype are increasing their pathogenicity.

Birds are also able to shed the virus for longer periods of time before their death, increasing the transmissibility of the virus.

Infected birds transmit H5N1 through their saliva, nasal secretions, feces and blood. 

Other animals may become infected with the virus through direct contact with these bodily fluids or through contact with surfaces contaminated with them. 

H5N1 remains infectious after over 30 days at 0 °C (32 °F) (over one month at freezing temperature) or 6 days at 37 °C (99 °F) (one week at human body temperature); at ordinary temperatures it lasts in the environment for weeks. 

In Arctic temperatures, H5N1 does not degrade at all.

Because migratory birds are among the carriers of the highly pathogenic H5N1 virus, it is spreading to all parts of the world. 

H5N1 is different from all previously known highly pathogenic avian flu viruses in its ability to be spread by animals other than poultry.

Waterfowl can directly spreading this highly pathogenic strain to chickens, crows, pigeons, and other birds, and the virus was increasing its ability to infect mammals, as well. 

H5N1 bird flu virus can also pass through a pregnant woman’s placenta to infect the fetus.

The range of species also seems to be expanding, with reports for many species of wildfowl, seabirds and scavenging species.

Humans, have become infected with H5N1 bird flu strains in the past, these cases had ostensibly been caused by direct exposure to infected birds, such as through consumption of birds by wildlife or exposure to infected poultry by farmers. 

As of May 2020, the WHO reported a total of 861 confirmed human cases which resulted in the deaths of 455 people since 2003.[5]

H5N1 has had a significant effect on human society, especially the financial, political, social, and personal responses to both actual and predicted deaths in birds, humans, and other animals. 

Billions of dollars are being raised and spent to research H5N1 and prepare for a potential avian influenza pandemic. 

Over $10 billion have been spent and over 200 million birds have been killed to try to contain H5N1.

Fever a common symptom.

Leukopenia, lymphopenia and thrombocytopenia are common.

H5N1 viruses are evolving rapidly but the direction of their evolution is not presently clear as to the increase in mammalian virulence.

Difficult to spread from person to person and requires a prolonged period of contact to do so.

To cause a pandemic the virus would have to adapt to human hemagglutin receptors and acquire human transmissibility.

Patients given early treatment with oseltamivir have the best chance of surviving the infection.

Oseltamivir routinely provided to persons traveling to regions where disease is endemic.

Corticosteroids not effective in the management of this disease and may add complications.

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