Avian influenza

For more information about seasonal human influenza virus that is not associated with animal exposure, see Influenza

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yazan Daaboul, M.D., Serge Korjian M.D., Gerald Chi, M.D.

Avian influenza is caused by influenza A virus. Influenza belongs to the Orthomyxoviridae family. Influenza A is an enveloped, pleomorphic (spherical and filamentous forms) virus that contains a linear, segmented (8 segments), negative-sense, single-stranded RNA genome. The genome is composed of 8 segmented genes that encode 11 proteins. The World Health Organization (WHO) reports an incidence of 3 to 5 million cases of severe influenza disease annually, including 250,000 to 500,000 deaths every year. The majority of cases of avian influenza infection in humans have resulted from contact with infected poultry or contaminated environments. Human-to-human transmission is still rare and inefficient. Influenza virus is transmitted in aerosols of respiratory secretions. The hemagglutinin (HA) protein on the viral surface functions as a receptor binding site and binds to host receptors that contain sialic acid to allow viral fusion to the host cell in the respiratory tract, while the neuraminidase (NA) enzyme cleaves progeny virions from host cell receptors. Viral proteins are, at least in part, responsible for down-regulation of cytotoxic T-cell activity, evasion of immune responses, and activation of cytokines and pro-inflammatory mechanisms that contribute to host tissue injury. Classification of avian influenza may be based on either the pathogenicity of the virus (low pathogenicity vs. high pathogenicity) or the viral genetic subtypes (H5 vs. H7 vs. H9). Following exposure to the avian influenza virus, an incubation period of 2 to 3 days for H5N1 and 2 to 8 days for H7N9 precedes the onset of symptoms. The majority of patients present with with high-grade fever, cough, headache, sore throat, vomiting, diarrhea, and abdominal pain. Approximately 50% of patients with avian influenza develop severe complications such as acute respiratory distress syndrome, acute kidney injury, sepsis, and multiple organ dysfunction syndrome. Some strains of avian influenza virus are associated with a mortality rate as high as 60% of infected individuals. Patients without complicated disease usually recover within 3 to 5 days with no sequelae. Diagnostic tests available for avian influenza include viral culture, serology, rapid antigen testing, polymerase chain reaction (PCR), immunofluorescence assays, or other molecular assays. Neuraminidase inhibitors can reduce the duration of viral replication and improve survival among patients with avian influenza. In cases of suspected avian influenza, oseltamivir, zanamivir, or peramivir should be administered as soon possible, preferably within 48 hours of symptom-onset. Seasonal influenza (human influenza) vaccination will not prevent infection with avian influenza A viruses, but can reduce the risk of co-infection with human and avian influenza A viruses. The optimal way to prevent infection with avian influenza A viruses is to avoid sources of exposure, such as infected poultry, whenever possible.

Avian influenza was first described by Perroncito in 1878 in northern Italy following an outbreak of contagious disease of poultry. In 1918, the avian-descended influenza A H1N1 caused the first major human influenza pandemic. The first avian influenza A H5N1 virus infection in humans was described in 1997 in Hong Kong, where 18 cases were documented (including 6 deaths). The first human-to-human transmission of avian influenza infection was described in 2003 during the outbreaks in Southeast and Central Asia.

All reported cases of avian influenza are caused by influenza A virus. The genome of influenza A consists of 8 RNA gene segments, which encode 11 proteins, including hemagglutinin, neuraminidase, non-structural proteins, matrix proteins, polymerase proteins, and nucleoprotein). Influenza virus is transmitted in aerosols of respiratory secretions. The HA protein on the viral surface functions as a receptor binding site and binds to host receptors that contain sialic acid to allow viral fusion to the host cell in the respiratory tract. Following fusion, viral replication typically takes place within 1 day, and polymerase proteins and nucleoproteins are involved in viral replication, whereas the matrix protein is responsible for viral assembly prior to viral release via cytolytic or apoptotic mechanisms. Viral proteins are, at least in part, responsible for down-regulation of cytotoxic T-cell activity, evasion of immune responses, and activation of cytokines and pro-inflammatory mechanisms that contribute to host tissue injury. Avian influenza undergoes antigenic drifts and shifts that ultimately result in genetic reassortment and capacity to reinfect the same host.

To date, only influenza type A has been associated with avian influenza. Neither influenza B nor influenza C is associated with avian influenza. Classification of avian influenza may be based on either the pathogenicity of the virus (low pathogenicity vs. high pathogenicity) or the viral genetic subtypes (H5 vs. H7 vs. H9).

Avian influenza is caused by influenza A virus. Neither influenza B nor influenza C causes avian influenza. Influenza belongs to the Orthomyxoviridae family. Influenza is an enveloped, pleomorphic (spherical and filamentous forms) virus that contains a linear, segmented (8 segments), negative-sense, single-stranded RNA genome. The genome is composed of 8 segmented genes that encode 11 proteins.

Avian influenza should be differentiated from the following diseases or pathogens that cause upper or lower respiratory tract infection or flu-like illness, such as other influenza viruses, such as human or swine influenza, other viral, bacterial, fungal, and parasitic agents that are typically associated with nasopharyngeal and respiratory tract infections, and non-infectious causes, such as asthma, chronic obstructive pulmonary disease (COPD), drug adverse effects, and cardiac causes.

The World Health Organization (WHO) reports an incidence of 3 to 5 million cases of severe influenza disease annually, including 250,000 to 500,000 deaths every year. The case fatality rate per outbreak is highly variable and may range from less than 1 to more than 200 per 100,000 cases. Influenza may infect patients of all age groups, but elderly patients > 65 years, young children (especially patients < 2 years of age), and adolescents are at high risk of developing complications and death. There is no racial or gender predilection for avian influenza infection.

The majority of cases of avian influenza infection in humans have resulted from contact with infected poultry, or contaminated environments. Human to human transmission is still rare and inefficient.

Following exposure to the avian influenza virus, an incubation period of 2 to 3 days for H5N1 and 2 to 8 days for H7N9 delays the onset of symptoms. The majority of patients present with with a high grade fever, cough, headache, sore throat, vomiting, diarrhea, and abdominal pain. Approximately 50% of patients with avian influenza develop severe complications such as acute respiratory distress syndrome, renal failure, sepsis, and multiple organ dysfunction syndrome. Some strains of avian influenza virus are associated with a mortality rate as high as 60% of infected individuals. Patients without complicated disease usually recover within 3 to 5 days with no sequelae.

Avian influenza virus infection is associated with a wide range of illness from conjunctivitis only, to influenza-like illness, to severe respiratory illness (e.g. dyspnea, pneumonia, acute respiratory distress, viral pneumonia, respiratory failure) with multi-organ disease, sometimes accompanied by nausea, abdominal pain, diarrhea, vomiting, and occasionally neurologic impairment (altered mental status or seizures).

Physical examination may reveal fever, tachycardia, tachypnea, and other findings suggestive of complications affecting multiple organ systems.

Diagnostic tests available for influenza include viral culture, serology, rapid antigen testing, polymerase chain reaction (PCR), immunofluorescence assays, and other molecular assays. Sensitivity and specificity of any test for influenza might vary by the laboratory that performs the test, the type of test used, and the type of specimen tested. Among respiratory specimens for viral isolation or rapid detection, nasopharyngeal specimens are typically more effective than throat swab specimens. As with any diagnostic test, results should be evaluated in the context of other clinical and epidemiologic information available to healthcare providers.

Chest radiograph may demonstrate findings suggestive of acute respiratory distress syndrome or pneumonia.

Other diagnostic test for influenza include molecular assays, such as RT-PCR. New technologies being pursued include those that examine influenza viruses at the molecular level. By examining the genetic makeup of influenza viruses, such tests could identify both the virus type and subtype simultaneously.

Neuraminidase inhibitors can reduce the duration of viral replication and improve survival among patients with avian influenza. In cases of suspected avian influenza, oseltamivir, zanamivir, or peramivir should be administered as soon possible, preferably within 48 hours of symptom onset.^[1]

Seasonal influenza vaccination will not prevent infection with avian influenza A viruses, but can reduce the risk of co-infection with human and avian influenza A viruses. The optimal way to prevent infection with avian influenza A viruses is to avoid sources of exposure whenever possible. Most human infections with avian influenza A viruses have occurred following direct close or prolonged contact with sick or dead infected poultry. Chemoprophylaxis with influenza antiviral medications can be considered for all exposed persons. Decisions to initiate antiviral chemoprophylaxis should be based on clinical judgment, with consideration given to the type of exposure and to whether the exposed person is at high risk for complications from influenza.

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For more information about seasonal human influenza virus that is not associated with animal exposure, see Influenza

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.

Avian influenza was first described by Perroncito in 1878 in northern Italy following an outbreak of contagious disease of poultry. In 1918, the avian-descended influenza A H1N1 caused the first major human influenza pandemic. The first avian influenza A H5N1 virus infection in humans was described in 1997 in Hong Kong, where 18 cases were documented (including 6 deaths). The first human-to-human transmission of avian influenza infection was described in 2003 during the outbreaks in Southeast and Central Asia.

• Avian influenza was first described by Perroncito in 1878 in northern Italy following an outbreak of contagious disease of poultry.^[1] In 1984 and 1901, subsequent outbreaks were reported in Italy, Germany, Austria, Belgium, and France.^[1]
• The first major human influenza (influenza A H1N1) pandemic was reported in 1918. The infleunza was an avian-descended virus that underwent adaptive mutations of unknown mechanisms.
• All viral forms were considered highly pathological avian influenza (HPAI) forms of H7 subtype until mid-1950s. After that, other H subtypes were subsequently isolated. In 1960, a new less virulent “N” subtype of avian influenza was isolated in Germany.^[1]

• The first influenza A H5N1 virus infection in humans was described in 1997 in Hong Kong, where 18 cases were documented (including 6 deaths).^[2][3]
• In 2003, the largest non-H5N1 outbreak occurred in Netherlands, where 89 cases were documented (including 1 death). It is hypothesized that during the Netherlands outbreak, the first human-to-human transmission may have occurred.^[4]
• In 2003, human-to-human transmission of avian influenza was first reported during the influenza A H5N1 outbreaks in Southeast and Central Asia.
• It has been speculated that following genetic mutations, the avian influenza virus may be evolving into more virulent and fatal forms, with increased rates of severe clinical manifestations.^[5][6]

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For more information about seasonal human influenza virus that is not associated with animal exposure, see Influenza

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.

To date, only influenza type A has been associated with avian influenza. Neither influenza B nor influenza C is associated with avian influenza. Classification of avian influenza may be based on either the pathogenicity of the virus (low pathogenicity vs. high pathogenicity) or the viral genetic subtypes (H5 vs. H7 vs. H9).

Classification of avian influenza may be based on either the pathogenicity of the virus or the viral genetic subtypes. To date, only influenza type A has been associated with avian influenza.

Avian influenza may be classified based on the pathogenicity of the virus:

• Low pathogenic avian influenza (LPAI)

Mild/no clinical manifestations among humans

May convert to highly pathogenic avian influenza

• Highly pathogenic avian influenza (HPAI)

Moderate/severe clinical manifestations among humans

Viral subtypes H5 and H7 are associated with HPAI

• To date, only influenza type A has been associated with avian influenza. Neither influenza B nor influenza C is associated with avian influenza.
• Although avian influenza has many subtypes of haemagglutinin (HA) and neuraminidase (NA), only 3 subtypes have been associated with human infections.
• The table below lists the subtypes of influenza A that have been associated with avian influenza in humans:^[1][2][3]

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For more information about seasonal human influenza virus that is not associated with animal exposure, see Influenza

For more details about the structure and morphology of the influenza A virus, click here

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]; Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.

All reported cases of avian influenza are caused by influenza A virus. The genome of influenza A consists of 8 RNA gene segments, which encode 11 proteins, including hemagglutinin, neuraminidase, non-structural proteins, matrix proteins, polymerase proteins, and nucleoprotein). Influenza virus is transmitted in aerosols of respiratory secretions. The HA protein on the viral surface functions as a receptor binding site and binds to host receptors that contain sialic acid to allow viral fusion to the host cell in the respiratory tract. Following fusion, viral replication typically takes place within 1 day, and polymerase proteins and nucleoproteins are involved in viral replication, whereas the matrix protein is responsible for viral assembly prior to viral release via cytolytic or apoptotic mechanisms. Viral proteins are, at least in part, responsible for down-regulation of cytotoxic T-cell activity, evasion of immune responses, and activation of cytokines and pro-inflammatory mechanisms that contribute to host tissue injury. Avian influenza undergoes antigenic drifts and shifts that ultimately result in genetic reassortment and capacity to reinfect the same host.

Data regarding the exact pathogenesis of avian influenza infection in hosts is limited.

All reported cases of avian influenza are caused by influenza A virus.^[1] The genome of influenza A consists of 8 gene segments, which encode 11 proteins^[1]:

• Hemagglutinin (HA): Surface protein that acts as a receptor binding site. HA is targeted by host antibodies to neutralize the virus.^[1][2][3]
• Neuraminidase (NA): Cleaves progeny virions from host cell receptors.^[1]
• Polymerase proteins: PB1, PB2, PA, and PB1-F2. These proteins form the polymerase complex. Together with the NP protein, form the ribonucleoprotein (RNP) complex to induce replication and transcription. Additionally, PB1-F2 has a role in inducing apoptosis.^[1][4]
• Nucleoprotein (NP): Together with the polymerase proteins, NP forms the RNP complex to induce replication and transcription.^[1]
• Non-structural proteins: NS1 and NS2. NS1 processes mRNA and helps the virus evade the host immune responses. NS2 controls the exporting process of RNP from the host nucleus.^[1]
• Matrix proteins: M1 and M2. M1 has a role in viral assembly. M2 controls pH in the Golgi body.^[1]

• Influenza virus is transmitted in aerosols of respiratory secretions.
• Avian influenza A viruses may be transmitted from animals to humans in two main ways:
  1. Directly from birds or from avian virus-contaminated environments to humans.
  2. Through an intermediate host, such as a pig.

• The HA protein (receptor binding site) on the viral surface binds to host receptors that contain sialic acid.^[3]
• The precursor HA molecule undergoes proteolytic activation and cleaves to produce 2 molecules: HA1 and HA2.
• Following proteolytic activation, the virus fuses with the host cell.
• The number of residues at the cleavage site is directly associated with the virulence of the virus (Highly cleavable HA with more residues at the cleavage site is thought to be activated by intracellular proteases and result in systemic infections).

• Following fusion, viral replication typically takes place within 1 day in the upper and lower respiratory tracts, including the nasopharynx, trachea, and lungs. Less commonly, replication occurs in extrapulmonary organs, including the intestines, brain, heart, or placenta.^[2][3]
• Similar to human influenza, avian influenza replicates intracellularly via cytolytic or apoptotic mechanisms.^[2]
• The poylmerase proteins are the main constituents of the polymerase complex that is involved in viral replication. NP encapsulates the RNA gene segments, which allows these segments to be recognized by the polymerase complex.^[4]
• During replication, NS proteins play a major role in evading the host immune responses by deactivating immune responses mediated by pro-inflammatory cytokines.^[4]
• Viral replication is inversely associated with outcomes among humans, where increased viral loads are associated with severe/fatal clinical disease.^[1]
• Following replication, the matrix proteins, which are present near the viral envelope, assemble the newly synthesized viruses.^[5]
• M2 provides the adequate pH in the Golgi apparatus for the viruses to replicate and assemble. Mutations in M2 protein have been associated with adaptive mechanisms of the virus to infect new hosts.^[5]

Following infection, the expression of cytokines and chemokines in the lungs significantly increases. The exaggerated up-regulation of these cytokines and chemokines may partly be responsible for the tissue injury associated with the influenza virus.^[1] The expression of the following proteins increases with avian influenza infection^[1]:

• Tumor necrosis factor-α

• Macrophage inflammatory protein 1-α

• Interferon-γ and interferon-β
• IL-6

It is thought that following infection, the TRAIL death receptor ligand is activated and is responsible for triggering apoptosis.^[1] The time onset of apoptosis induction may vary among influenza subtypes; this delay may, at least in part, account for the prolonged and severe infection associated with certain subtypes.^[1]

• It is thought that the hemagglutinin of influenza virus is responsible for the suppression of perforin protein in cytotoxic T-cells.^[1]
• As perforin expression is reduced, the cytotoxic capacity of the T-cells is also reduced, the the T-cells ultimately fail to clear the influenza.

• These are small changes in the genes of influenza viruses that happen continually over time as the virus replicates.
• These small genetic changes usually produce viruses that are pretty closely related to one another, which can be illustrated by their location close together on a phylogenetic tree.
• Viruses that are closely related to each other usually share the same antigenic properties and an immune system exposed to an similar virus will usually recognize it and respond. (This is sometimes called cross-protection.)
• But these small genetic changes can accumulate over time and result in viruses that are antigenically different (further away on the phylogenetic tree).
• When this happens, the body’s immune system may not recognize those viruses.
• This process works as follows:

• A person infected with a particular flu virus develops antibody against that virus.
• As antigenic changes accumulate, the antibodies created against the older viruses no longer recognize the “newer” virus, and the person can get sick again.
• Genetic changes that result in a virus with different antigenic properties is the main reason why people can get the flu more than one time.

• This is also why the flu vaccine composition must be reviewed each year, and updated as needed to keep up with evolving viruses.

Adapted from CDC ^[6]

• Antigenic shift is an abrupt, major change in the influenza A viruses, resulting in new hemagglutinin and/or new hemagglutinin and neuraminidaseproteins in influenza viruses that infect humans.
• Shift results in a new influenza A subtype or a virus with a hemagglutinin or a hemagglutinin and neuraminidase combination that has emerged from an animal population that is so different from the same subtype in humans that most people do not have immunity to the new (e.g. novel) virus.
• Such a “shift” occurred in the spring of 2009, when an H1N1 virus with a new combination of genes emerged to infect people and quickly spread, causing a pandemic.
• When shift happens, most people have little or no protection against the new virus.
• While influenza viruses are changing by antigenic drift all the time, antigenic shift happens only occasionally.
• Influenza type A viruses undergo both kinds of changes
• Influenza type B viruses change only by the more gradual process of antigenic drift.

• 
  Antigenic Drift
  Click on the image to expand.
  Image courtesy of the National Institute of Allergy and Infectious Diseases (NIAID) [1]
• 
  Antigenic Shift
  Click on the image to expand.
  Image courtesy of the National Institute of Allergy and Infectious Diseases (NIAID) [2]

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For more information about seasonal human influenza virus that is not associated with animal exposure, see Influenza

For more details about the avian influenza transmission, replication, and mechanism of infection in humans, click here

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.

Avian influenza is caused by influenza A virus. Neither influenza B nor influenza C causes avian influenza. Influenza belongs to the Orthomyxoviridae family. Influenza is an enveloped, pleomorphic (spherical and filamentous forms) virus that contains a linear, segmented (8 segments), negative-sense, single-stranded RNA genome. The genome is composed of 8 segmented genes that encode 11 proteins.

Avian influenza is caused by influenza A virus. Neither influenza B nor influenza C causes avian influenza.

• The influenza virus belongs to the Orthomyxoviridae family.

• The influenza A virus contains linear, segmented, negative-sense, single-stranded RNA.
• The RNA genome is segmented into 8 distinct segments.
• The total genomic length is approximately 13,000 nucleotides (range from 12,000 to 15,000).
• The genome is composed of 8 genes that encode 11 proteins.

The genome of influenza A consists of 8 gene segments, which encode 11 proteins^[1]:

• Hemagglutinin (HA): Surface protein that acts as a receptor binding site. HA is targeted by host antibodies to neutralize the virus.^[1][2][3]
• Neuraminidase (NA): Cleaves progeny virions from host cell receptors.^[1]
• Polymerase proteins: PB1, PB2, PA, and PB1-F2. These proteins form the polymerase complex. Together with the NP protein, form the ribonucleoprotein (RNP) complex to induce replication and transcription. Additionally, PB1-F2 has a role in inducing apoptosis.^[1][4]
• Nucleoprotein (NP): Together with the polymerase proteins, NP forms the RNP complex to induce replication and transcription.^[1]
• Non-structural proteins: NS1 and NS2. NS1 processes mRNA and helps the virus evade the host immune responses. NS2 controls the exporting process of RNP from the host nucleus.^[1]
• Matrix proteins: M1 and M2. M1 has a role in viral assembly. M2 controls pH in the Golgi body.^[1]

• The influenza virus contains an envelope.
• The influenza virus is pleomorphic with spherical and filamentous forms with particles that are approximately 80 nm to 120 nm in diameter.

Template:WH Template:WS

For more information about seasonal human influenza virus that is not associated with animal exposure, see Influenza

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.

Avian influenza should be differentiated from the following diseases or pathogens that cause upper or lower respiratory tract infection or flu-like illness, such as other influenza viruses, such as human or swine influenza, other viral, bacterial, fungal, and parasitic agents that are typically associated with nasopharyngeal and respiratory tract infections, and non-infectious causes, such as asthma, chronic obstructive pulmonary disease (COPD), drug adverse effects, and cardiac causes.

Influenza should be differentiated from the following diseases or pathogens that cause upper or lower respiratory disease or flu-like symptoms:^{[1][2][3][4][5][6][7]}

• Other influenza viruses, such as human influenza or swine influenza
• Other infectious agents, including viruses, bacteria, fungi, and parasites, that are typically responsible for respiratory illness
  • Adenoviruses
  • Anthrax (caused by B. anthracis)
  • Arenaviruses
  • Cytomegalovirus (CMV)
  • Chlamydia pneumoniae
  • Coronaviruses (responsible for SARS and MERS)
  • Dengue fever
  • Echoviruses
  • Ebola virus infection
  • Hantavirus pulmonary syndrome
  • Herpes viruses
  • HIV disease
  • Histoplasmosis and other fungal causes of respiratory disease
  • Human metapneumovirus
  • Malaria
  • Measles
  • Parainfluenza virus
  • Poliovirus infection
  • Q fever
  • Rhinovirus
  • Respiratory syncytial virus
  • Other bacterial causes of nasopharyngeal and respiratory infection, such as S. pneumoniae, S. aureus, H. influenzae, M. pneumoniae, M. tuberculosis, L. pneumophila.

• Asthma
• Bronchiectasis
• Chronic obstructive pulmonary disease and emphysema
• Drugs, such as interferons, monoclonal antibodies, bisphosphonates, and chemotherapeutic agents
• Hematologic malignancies (leukemias and lymphomas)
• Myocarditis
• Metal fume fever
• Pericarditis
• Pulmonary embolism
• Vaccinations (typically transient and mild flu-like illness)

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For more information about seasonal human influenza virus that is not associated with animal exposure, see Influenza

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.

The World Health Organization (WHO) reports an incidence of 3 to 5 million cases of severe influenza disease annually, including 250,000 to 500,000 deaths every year. The case fatality rate per outbreak is highly variable and may range from less than 1 to more than 200 per 100,000 cases. Influenza may infect patients of all age groups, but elderly patients > 65 years, young children (especially patients < 2 years of age), and adolescents are at high risk of developing complications and death. There is no racial or gender predilection for avian influenza infection.

• The incidence of avian influenza is difficult to extrapolate from the annual incidence of influenza in general.
• The World Health Organization (WHO) reports an incidence of 3 to 5 million cases of severe influenza disease annually, including 250,000 to 500,000 deaths every year.

• The annual incidence may vary significantly depending on whether an influenza outbreak occurs or not.^[3]

• During outbreaks, the influenza may infect millions of individuals with an annual mortality rate that ranges between 15,000 (in 2009 influenza pandemic) and 100 million (in 1918 influenza pandemic).

• The case fatality rate per outbreak is also highly variable and may range from less than 1 to more than 200 per 100,000 cases.^[3]

• Influenza, including avian influenza, may infect patients of all age groups.^[3]

• Determination of specific at-risk patient populations depends on the virus subtype.

• High risk populations are elderly > 65 years, young children (especially patients < 2 years of age), and adolescents.

• There is no racial predilection for avian influenza infection.

• There is no gender predilection for avian influenza infection.

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For more information about seasonal human influenza virus that is not associated with animal exposure, see Influenza

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

The majority of cases of avian influenza infection in humans have resulted from contact with infected poultry, or contaminated environments. Human to human transmission is still rare and inefficient.

• The most important risk factor for human infection with avian influenza is exposure to infected live or dead poultry (whether direct or indirect) or to environments that may be contaminated, such as live bird markets. ^[1][2][3][4]
• Such exposure is highest among individuals that handle, slaughter, defeather infected poultry, or handle carcasses of infected poultry. ^[3]
• Preparing poultry for consumption, especially in household settings, is also an important risk factor.^[4]

• Other less substantiated risk factors include:
  • Consumption of dishes made of raw contaminated poultry^[2]
  • Lack of an indoor water source^[4]
  • Exposure to infected individuals^[2]
• The spread of avian influenza viruses from one ill person to another has been reported very rarely, and has been inefficient and not sustained.^[2]

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For more information about seasonal human influenza virus that is not associated with animal exposure, see Influenza

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Following exposure to the avian influenza virus, an incubation period of 2 to 3 days for H5N1 and 2 to 8 days for H7N9 delays the onset of symptoms. The majority of patients present with with a high grade fever, cough, headache, sore throat, vomiting, diarrhea, and abdominal pain. Approximately 50% of patients with avian influenza develop severe complications such as acute respiratory distress syndrome, renal failure, sepsis, and multiple organ dysfunction syndrome. Of the reported cases, about 60% of patients have died, particularly those who develop early complications. Patients without complicated disease usually recover within 3 to 5 days with no sequelae.

• Following initial exposure to the virus, the usual incubation period for the H5N1 avian influenza is approximately 2 to 3 days, but possibly as long as 17 days in some individuals. For the H7N9 avian influenza, the incubation period ranges from 2 to 8 days, with an average of 5 days.^[1]
• The majority of patients present with a high grade fever, cough, headache, sore throat, vomiting, diarrhea, abdominal pain. ^[1][2]
• The illness is has an very aggressive clinical course, often with rapid deterioration.^[2]
• Most patients develop significant lower respiratory tract involvement, with aggressive viral pneumonia, pleural effusions, and ARDS.^[2]
• The rate of complications is very high with approximately 50% of patients suffering from life-threatening complications.^[2]

Approximately 50% of patients with avian influenza develop one or more of the following complications:^[2]

• Pneumonia
• Acute pulmonary hemorrhage
• Pleural effusion
• Acute respiratory distress syndrome
• Acute renal failure
• Multiple organ dysfunction syndrome
• Sepsis / Septic shock
• Disseminated intravascular coagulopathy
• Reye’s syndrome

Of the human cases associated with the H5N1 outbreaks in poultry and wild birds in Asia and parts of Europe, the Near East, and Africa, about 60% of people reported to be infected with the virus have died. Most cases have occurred in previously healthy children and young adults.^[3] Patients with early complications are at a much higher risk of death, often from multiple organ dysfunction syndrome.^[2] Patients with no complications usually recover within 3 to 5 days with no sequelae.^[3]

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