Avian influenza A(H5N1): For health professionals

What health professionals need to know about avian influenza A(H5N1)

Outbreaks of avian influenza A(H5N1) in domestic and wild birds and some wild mammals have recently emerged and become widespread in Europe and North, Central and South America, including across Canada. Government authorities in Canada are currently responding to the outbreak of influenza A(H5N1) in farmed birds and wildlife across Canada.

Influenza A(H5N1) is a subtype of avian influenza virus that mainly infects birds, but causes rare and sporadic human cases.

Human cases of influenza A(H5N1) have primarily occurred due to zoonotic transmission through direct contact with infected birds (dead or alive) or contaminated environments. Human-to-human transmission is extremely rare.

Clinical illness caused by influenza A(H5N1) is predominately observed in children and young adults. The virus mainly affects the respiratory tract but can also cause gastrointestinal or central nervous system manifestations. Infection may progress to severe illness and can be fatal.

Clinicians and front-line laboratory personnel are encouraged to follow the Protocol for Microbiological Investigations of Severe Acute Respiratory Infections (SARI) to facilitate the diagnosis of severe respiratory infection caused by pathogens with epidemic potential.

Antivirals used to treat influenza can be effective in reducing morbidity and mortality, especially if administered early in the course of illness. Prophylactic use of influenza-specific antivirals (pre and post exposure) may prevent illness. Seasonal influenza vaccines do not offer protection against influenza A(H5N1).

Human infections of influenza A(H5N1) are notifiable under the International Health Regulations (2005). Provincial and Territorial public health authorities are required to report confirmed and probable human cases of influenza A(H5N1), irrespective of illness symptoms or severity, to the Public Health Agency of Canada (PHAC) within 24 hours of their own notification, as per the Emerging Respiratory Pathogens and Severe Acute Respiratory Infection (SARI) case report form. PHAC is required to report any human case detected in Canada to the World Health Organization according to the International Health Regulations (2005) requirements and timelines.

For detailed recommendations on public health management and reporting requirements, consult the appropriate local, provincial, or territorial health authorities.

Agent of Disease

Avian influenza A(H5N1) is a member of the Orthomyxoviridae family.

Influenza viruses are enveloped ribonucleic acid (RNA) viruses. Influenza virus strains can be classified according to their core proteins into influenza A, influenza B, influenza C, and influenza D. Influenza D is seen in animals, predominantly cattle; it is not known to cause illness in humans.

Influenza A viruses can be further subdivided according to their antigenic surface glycoproteins: HA (hemagglutinin) and NA (neuraminidase). To date, 16 HA and 9 NA influenza A subtypes have been detected in wild birds and poultry.

Avian influenza A(H5N1) is classified as highly pathogenic avian influenza (HPAI), based on the severity of illness caused in poultry.

Transmission

There are different ways that avian influenza A(H5N1) can be transmitted to humans.

According to the source of infection, transmission can be divided into:

Animal to human:

Individuals can be exposed to the virus through contact with infected birds, dead birds, or birds' secretions (mucus, saliva), blood and feces (as birds shed the virus in their secretions and feces). Transmission of the virus occurs via inhalation or contact with mucus membranes (e.g., eyes, nose, mouth).

Human infection has been reported after de-feathering of influenza A(H5N1) infected dead swans, and it has been determined that the influenza A(H5N1) virus can survive in feathers for several weeks in moderate temperatures, and over 5 months in cooler temperatures.

The ability of infected wild mammals to transmit avian influenza A(H5N1) to humans has not yet been determined. Although theoretically possible, there has never been a documented case of mammal-to-human influenza A(H5N1) transmission. Nonetheless, avian influenza detections in mammals and evidence of mutation or mammalian adaptation in the viral genome sequences from infected animals are important to monitor.

Mutations found within some of the Eurasian/North American reassortant influenza A(H5N1) strains circulating in North American birds and mammals in 2022 have been shown to enhance polymerase activity and replication in mammalian cells, help evade the immune response, and increase virulence in mice experimentally. As well, recent preliminary findings from pathogenicity and transmissibility studies indicate that the reassortant influenza A(H5N1) strains cause more severe illness in ferrets, increasing concerns about the potential for transmission to humans.

Foodborne transmission:

There have been rare reports of human cases of avian influenza A(H5N1) possibly associated with consumption of raw or undercooked contaminated poultry products, such as raw duck organs and duck blood.

It is important to note that there is no evidence to suggest that the consumption of fully cooked poultry, game meat or eggs could transmit the influenza A(H5N1) virus to humans. All evidence to date indicates that thorough cooking will kill the virus.

To limit any potential foodborne risks, all poultry, game meat and eggs should be thoroughly cooked to kill potential viruses, parasites and bacteria. Safe food handling practices, such as handwashing and keeping poultry, game meat, eggs and egg products separate from other food products to avoid cross contamination, should be followed.

Traditional foods such as wild geese and ducks and harvested wild eggs are important sources of food for many Canadians. Although the risk of being infected with avian influenza A(H5N1) from wild birds and eggs is low, hunters and people who handle, prepare and cook wild birds and eggs may be at a higher risk. Therefore, it is important for people who hunt and eat wild birds or gather wild eggs to take precautions to help reduce any risk.

Environmental exposure:

The majority of influenza A(H5N1) human cases have occurred after contact with infected poultry; however, some cases have been associated with exposure to contaminated environments, such as live bird markets and poultry farms.

Theoretically, humans could get infected with influenza A(H5N1) by exposure to contaminated water (i.e., inhalation, ingestion, conjunctival or intranasal inoculation), however the evidence to support this is limited. Environmental exposure through contaminated water (for example, bathing or swimming in household ponds, or lacking an indoor water source) has been suggested as a possible risk factor for human infection in a small number of influenza A(H5N1) studies.

Human to human:

Evidence of limited human-to-human transmission of influenza A(H5N1) (via close physical contact, for example within a household) has been suggested in previous outbreaks. Sustained human-to-human transmission of avian influenza A(H5N1) has never been observed.

Clinical manifestations

Avian influenza A(H5N1) in humans mainly affects the respiratory tract. However, it can manifest with gastrointestinal or central nervous system symptoms (e.g., encephalopathy). Clinical illness is seen predominantly in children and young adults.

Most human cases have reported a history of exposure to dead or ill poultry, and the incubation period after exposure is usually 1 to 5 days and up to 9 days.

The clinical manifestations of avian influenza A(H5N1) may include:

cough
fever
shortness of breath
diarrhea (in severe cases)
headache
myalgia
sore throat
rhinorrhea
mucosal bleeding
fatigue
jaundice
conjunctivitis

Imaging studies may show:

bilateral pulmonary infiltrates
segmental or lobular consolidation

Based on available human case data to date, the case fatality rate of avian influenza A(H5N1) is approximately 52%. Seroprevalence studies from endemic areas indicate that subclinical or mild infection may occur, with reports of seropositivity ranging from 0% up to 7% in people exposed to influenza A(H5N1), depending upon region and employment activities.

Respiratory failure is the most common cause of death. Other complications may include:

multiorgan failure
pulmonary hemorrhage
pneumothorax
pancytopenia

Diagnosis

Clinicians and front line laboratory personnel should consult their local public health unit and the "Protocol for Microbiological Investigations of Severe Acute Respiratory Infections (SARI)" for guidance on appropriate testing, recommended procedures, and prioritization for influenza A(H5N1) investigations if significant exposure history has been established.

Specimen collection types to be considered include: nasopharyngeal swab, throat swab, sputum, bronchoalveolar lavage, and endotracheal secretions.

While nasopharyngeal swabs are the primary specimen type for seasonal influenza viruses, based on experiences with the pandemic H1N1 and avian influenza infections, multiple specimen types should be collected in cases of severe respiratory infection with a negative nasopharyngeal swab

Influenza A and B RT-PCR with subtyping (H5) should be the primary method for detection of avian influenza A(H5N1). Any positive samples must be shared with the National Microbiology Laboratory (NML) for confirmatory testing and analysis to fulfill NML’s obligations as a National Influenza Centre and Canada's obligations under the International Health Regulations and other agreements.

Rapid Influenza Diagnostic Tests should not be used to rule out influenza A infection. In addition to suboptimal sensitivity of these tests, the ability to detect novel influenza viruses, such as avian influenza viruses, is unknown.

Treatment

Antiviral agents can be used to treat suspected, probable, or confirmed avian influenza A(H5N1) cases. The ideal time to begin antiviral treatment is within the first 48 hours of illness onset. Treatment can be initiated while awaiting confirmatory test results and should not be delayed.

There are several antiviral options for the treatment of influenza A(H5N1):

Neuraminidase inhibitors (oseltamivir, zanamivir, and peramivir)
Amantadine
Baloxavir

Individual characteristics and case presentation should be considered when selecting the appropriate antiviral agent. Oseltamivir, zanamivir, and amantadine are available for use in Canada. Baloxavir and intravenous peramivir may be requested through the Special Access Program and approved on a case-by-case basis.

To date, there have been no clinical trials measuring the outcome of antiviral use in individuals infected with avian influenza A(H5N1). However, data from animal models and human observational studies have suggested a morbidity and mortality benefit to the use of oseltamivir as an antiviral agent.

Due to increased reports of antiviral resistance, amantadine is not recommended for use as a monotherapy for avian influenza. Emergence of oseltamivir resistance has also been reported. Combination therapy of antivirals with different mechanisms of action may be considered for select cases at risk of antiviral resistant infection with monotherapy (e.g., immunocompromised).

For more information on the indications, safety, and use of antivirals in special populations, refer to the Product Monographs available on Health Canada's Drug Product Database.

In addition to antivirals, some cases may require respiratory support. Presently, there is insufficient evidence to suggest added benefit from adjunctive therapies in patients with avian influenza A(H5N1) (i.e., corticosteroids, macrolide antibiotics, and passive immune therapy).

Prevention and control of transmission within healthcare settings

Refer to PHAC's Routine Practices and Additional Precautions for Preventing the Transmission of Infection in Healthcare Settings for recommendations on routine practices to prevent transmission when providing patient care. Recommendations in this guideline should be read in conjunction with relevant provincial, territorial, and local legislation, regulations, and policies.

Public health management

Upon notification of an avian influenza A(H5N1) outbreak with potential human health implications, it is recommended that public health authorities initiate an investigation and, informed by the initial findings from the epidemiologic assessment of the outbreak, implement appropriate public health measures to protect human health.

For management of people who have been exposed to infected animals (wild or domestic) or their environment:

provide advice on self-monitoring for symptoms for 10 days after last exposure to infected animals or contaminated environment
evaluate for antiviral prophylaxis
if influenza-like symptoms develop, obtain diagnostic specimens

For management of human cases in the community:

complete a case report form as required
facilitate collection of appropriate diagnostic specimens
provide information to the case about their illness and who to call and where to go if their illness becomes more severe
instruct the case to self-isolate
provide information on preventing infection spread to other household contacts (e.g., respiratory etiquette, hand hygiene, etc.)
facilitate access to early antiviral treatment
conduct active surveillance and document course of illness as required
identify any close contacts (e.g., household contacts)

close contacts are individuals who have been in close proximity of a confirmed or probable case of influenza A(H5N1). They could have also occupied the same area for a prolonged duration of time, or have had direct contact with infectious secretions of a confirmed or probable case of influenza A(H5N1)

The following resource provides additional information on human case and contact management of suspected human infections associated with an animal influenza A(H5N1) outbreak:

Case identification and reporting

Clinicians and front-line laboratory personnel should follow the Protocol for Microbiological Investigations of Severe Acute Respiratory Infections (SARI). Influenza positive specimens outside the influenza season or obtained from patients with a history of exposure to a potential animal source of influenza (e.g., domestic chickens, ducks, wild birds), should be routinely submitted to the National Microbiology Laboratory (NML) for characterization.

Technical information on avian influenza A(H5N1) and laboratory safety can be found in the Pathogen safety data sheets: Infectious substances – Influenza A virus subtypes H5, H7 and H9.

Provincial/territorial public health authorities are:

advised to continue vigilance for the recognition, reporting and prompt investigation of patients with Severe Acute Respiratory Illness (SARI)
required to report confirmed and probable human cases of avian influenza A(H5N1), irrespective of illness symptoms or severity, to PHAC within 24 hours of their own notification as per the Emerging Respiratory Pathogens and Severe Acute Respiratory Infection (SARI) case report form

Surveillance

For detailed background and recommendations on enhanced SARI surveillance in hospitals, please consult your local, provincial or territorial health authorities.

PHAC reports any cases of human influenza A of avian origin that are notified globally and within Canada each month in the Human Emerging Respiratory Pathogens Bulletin.

Canada uses a One Health approach to track avian influenza activity in Canada and around the world.

Canada continually monitors:

outbreaks of avian influenza in poultry and wildlife
human cases of avian influenza

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