Updated March 27, 2023
NCCID Disease Debriefs provide Canadian public health practitioners and clinicians with up-to-date reviews of essential information on prominent infectious diseases for Canadian public health practice. While not a formal literature review, information is gathered from key sources including the Public Health Agency of Canada (PHAC), the USA Centers for Disease Control and Prevention (CDC), the World Health Organization (WHO) and peer-reviewed literature.
This disease debrief was prepared by Shyama Nanayakkara and Wendy Xie. Questions, comments, and suggestions regarding this disease brief are most welcome and can be sent to firstname.lastname@example.org
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Questions Addressed in this debrief:
- What are important characteristics of the H5N1 Avian Influenza virus?
- What is happening with current outbreaks of H5N1 Avian Influenza?
- What is the current risk for Canadians from H5N1 Avian Influenza?
- What measures should be taken for a suspected H5N1 Avian Influenza case or contact?
What are the important characteristics of the H5N1 Avian Influenza virus?
Influenza viruses are enveloped ribonucleic acid (RNA) viruses of the Orthomyxoviridae family, which can be classified based on their core proteins into influenza A, B, C, and D strains. Avian influenza, known informally as avian flu, is a bird flu caused by the influenza A virus which can infect people.
Avian influenza (AI) viruses are further subdivided according to their antigenic surface glycoproteins: hemagglutinin (HA) and neuraminidase (NA). To date, 16 HA and 9 NA influenza A subtypes have been detected in wild birds and poultry, which are the natural carriers of avian influenza viruses. Avian influenza is classified as highly pathogenic avian influenza (HPAI) or low pathogenic avian influenza (LPAI) based on the severity of the illness caused in poultry. H5N1 AI is a highly pathogenic avian influenza virus that is easily transmitted between birds and is a zoonotic disease (a disease that transmits from animals to people), but it is not well adapted to mammals. There have been reports of possible limited human-to-human transmission, but there has been no evidence of ongoing transmission between people.
Though rare, H5N1 avian influenza may spread to humans after close contact with infected birds or highly contaminated environments such as poultry farms or live bird markets. The virus is spread by infected birds through their saliva, mucosa, and feces. Humans can become infected with the viruses if the virus enters the eyes, nose, or mouth, or is inhaled. This occurs if a virus is in the air (in the form of droplets or possibly dust) or if a person touches something contaminated with a virus and then touches their mouth, eyes, or nose.
Signs, Symptoms and Severity
Signs and symptoms of H5N1 avian influenza A in humans have ranged from no symptoms to severe illness and can be fatal. Clinical illness caused by H5N1 AI is usually observed in children and young adults. The virus mainly affects the respiratory tract, and sometimes the gastrointestinal tract or central nervous system. The incubation period ranges from 2 to 5 days and may be up to 17 days. According to available human case data, the case fatality rate of H5N1 AI infection is approximately 52%.
Uncomplicated H5N1 highly pathogenic AI virus infection in humans can start with symptoms of:
- Shortness of breath
- Fever, greater than 38 °C
- Aching muscles
- Runny nose
- Sore throat
Atypical early symptoms may include:
- Conjunctivitis (red eyes)
- Bleeding gums
In rare cases, the infection may progress quickly to:
- Severe respiratory illness, which can include:
- Acute respiratory distress syndrome
- Difficulty breathing
- Pulmonary hemorrhage
- Neurological changes (changed mental state or seizures)
- Multi-organ failure
- Septic shock
Imaging studies may show:
- Bilateral pulmonary infiltrates
- Segmental or lobular consolidation
A laboratory test is required to diagnose H5N1 avian influenza A. Specimen collection can include nasopharyngeal swab (most common), throat swab, sputum, bronchoalveolar lavage, and endotracheal secretions. 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 in this case) should be the primary method for detection of H5N1 avian influenza A. 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 for laboratory diagnosis. In addition to suboptimal sensitivity of these tests, the ability to detect novel influenza viruses, such as avian influenza viruses, is unknown.
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 infections caused by pathogens with epidemic potential.
Infected individuals with severe infection need to be hospitalized. Current antiviral flu medications can be used to treat H5N1 avian influenza A and can be effective in reducing morbidity and mortality. It is important that antiviral medications be taken as early as possible, ideally within 48 hours of getting sick.
The use of antiviral medications can:
- Reduce influenza symptoms.
- Shorten the length of illness.
- Potentially reduce serious complications
According to the Public Health Agency of Canada (PHAC), prophylactic use of influenza-specific antivirals (pre- and post-exposure) may prevent illness. There are also several antiviral options for the treatment of H5N1 HPAI, including neuraminidase inhibitors (oseltamivir, zanamivir, and peramivir), Amantadine, and 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, no clinical trials have measured the outcomes of antiviral use in individuals infected with H5N1 avian influenza A.
Amantadine is not recommended for use as a monotherapy for avian influenza due to increased reports of antiviral resistance. The 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 individuals). In addition to antivirals, some cases may require respiratory support. There is limited evidence for the benefits of adjunctive therapies in patients with H5N1 avian influenza A (i.e., corticosteroids, macrolide antibiotics, and passive immune therapy).
Corticosteroids are not recommended for routine use unless indicated for other reasons (for example, asthma), because they have been linked to prolonged viral clearance and immunosuppression, which can lead to bacterial or fungal superinfection. Antiviral treatment should not be delayed while waiting for laboratory test results.
Avian influenza A (H5N1) virus is commonly found in birds across African and Asian countries, and more recently in Europe and North, Central and South America, including across Canada. Wild birds in Canada and throughout the world are the natural carriers of avian influenza viruses. Ongoing circulation of H5 and H7 avian influenza A viruses are of human public health concern as these viruses can cause severe disease in people and can mutate to increase human-to-human transmissibility. Although infections in humans as the result of close and prolonged contact with another infected individual have been reported, there has been no evidence of sustained human-to-human transmission. Since the outbreaks of H5N1 HPAI in humans in Hong Kong, South Korea, Vietnam, Japan, Thailand, Laos, Cambodia, China, Indonesia, and Malaysia in 2003, the World Health Organization (WHO) has reported a number of cases involving avian-to-human transmission spreading from Southeast Asia to North and West China, reaching as far as Eastern Europe and Northern Africa. A total of 868 confirmed human H5N1 HPAI infections and 457 deaths were reported to WHO between 2003-2023, most of which were reported between 2003-2019 (861 infections, 455 deaths).
H5N1 viruses belonging to clade 18.104.22.168b have been circulating globally for a number of years but frequent outbreaks began in North American birds and poultry flocks in early May 2022. As of March 10, 2023, clade 22.214.171.124b H5N1 viruses have been detected in 16 countries in Latin America and the Caribbean as well as the United States and Canada.
Direct or indirect exposure to infected live or dead poultry or contaminated environments, such as live bird markets, appears to be the primary risk factor for human infection. Slaughtering, defeathering, handling infected poultry carcasses, and preparing poultry for consumption, are all risk factors. A few human cases of H5N1 have been linked to the consumption of dishes made with raw, contaminated poultry blood. It is critical to control the spread of avian influenza viruses in poultry to reduce the risk of human infection.
Prevention and Control
The annual seasonal influenza vaccine (“flu shot”) does not provide protection against avian influenza. The risk of H5N1 avian influenza virus infection is low for the general public, however basic precautions are always recommended to prevent transmission of zoonotic diseases:
- Avoid close contact and do not touch, feed, or handle wild birds.
- If contact is unavoidable, wear gloves or use a doubled plastic bag and avoid contact with blood, body fluids and feces.
- Remove worn gloves and wash your hands thoroughly with soap and water. If soap and water aren’t available, use a hand sanitizer containing at least 60% alcohol.
- Always wash your hands after being in an area where birds and other wildlife are living or nesting, such as in parks or zoos
- Children should be monitored to ensure proper handwashing.
- Pets should be kept away from birds and wildlife and their feces.
If working with poultry, wild birds, or other wildlife that are suspected or confirmed to be infected with H5N1 avian influenza A, the following precautions should be taken during handling or when working in heavily contaminated environments:
- Wear masks and eye protection to protect your eyes, nose and mouth from contaminated dust, feathers, secretions, and feces.
- Wear other protective clothing, such as gloves, boots, and coveralls.
- Prior to cleaning up contaminated areas, mist dry areas with low pressure water to prevent fecal matter, dust, and feathers from being stirred up into the air.
- Change clothing and footwear, and wash hands thoroughly with soap and water before moving onto other activities.
- Follow any additional occupational health guidelines, as directed by your occupational health provider.
Exposure to avian influenza can occur when handling wild birds and some wild mammals, therefore it is recommended that hunters and trappers take precautions when de-feathering, cleaning and preparing wild game. Thoroughly cooking meat, organs and eggs harvested from wildlife will kill the avian influenza virus.
Human infections of H5N1 avian influenza A 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.
Seasonal influenza vaccines do not offer protection against influenza A(H5N1). The hemagglutinin (HA) protein of recently detected clade 126.96.36.199b HPAI A(H5N1) viruses in birds and mammals is nearly identical or, in many samples, identical to an H5 candidate vaccine virus (CVV) produced by the CDC. if needed and would provide good protection against the clade 188.8.131.52b HPAI A(H5N1) viruses circulating in birds. This H5 CVV is already available and has been shared with the vaccine manufacturers.
Although H5N1 avian influenza viruses do not currently pose a significant threat to the general population, sporadic human infections are expected to continue due to the potential for influenza viruses to evolve quickly and their widespread global prevalence in wild birds and poultry outbreaks.
What is happening with current outbreaks of H5N1 Avian Influenza?
One confirmed H5N1 avian influenza A infection in Colorado, USA was previously reported in April 2022. The Canadian Food Inspection Agency (CFIA) is currently responding to cases of H5N1 highly pathogenic avian influenza (HPAI) in farmed birds across Canada. In the WHO Summary and risk assessment report for the period of January 27 – March 3, 2023, there were no confirmed cases of H5N1 HPAI infection in humans in Canada or USA, and three cases of infection in Cambodia, China, and Ecuador. The introduction of avian influenza poses a threat animal and human health, requiring both sectors to be involved in surveillance and response preparations.
What is the current risk for Canadians?
In early 2014, one case of H5N1 avian influenza infection in a Canadian resident resulting in mortality was reported after the resident had returned from travel in China. Since this case in 2014 up to March 3, 2023, no human infections of HPAI H5 viruses have been identified in Canada, and the risk of infection for the general public remains low.
In the United States, outbreaks of avian influenza in backyards, farms, and commercial birds continues to be monitored. H5N1virus was detected in 6,444 wild birds across 49 states between January 2022 and March 15, 2023, as well as in 799 commercial and backyard flocks across 47 states.
Canada currently monitors for notifiable avian influenza through:
- Wild bird surveillance
- Passive surveillance in domestic poultry when clinical signs suggestive of notifiable avian influenza are reported
- Targeted surveillance when notifiable avian influenza is detected
- Pre-slaughter surveillance in commercial poultry (chickens and turkeys)
- Hatchery supply flock surveillance
- Voluntary enhanced surveillance in the poultry genetic exporters sector.
Based on preliminary laboratory studies, the HPAI H5 viruses causing the poultry outbreaks are not well-adapted to humans, and infection does not occur when consuming thoroughly cooked poultry and eggs. However, sporadic cases of human respiratory illness with high mortality from infections with other closely related HPAI H5 viruses (e.g., H5N1, H5N6) have occurred in other countries. Most human infections with HPAI viruses were after exposures consisting of either 1) direct physical contact with infected birds or surfaces contaminated by the viruses; 2) being in close proximity (e.g., within about 6 feet) to infected birds; or 3) visiting a live poultry market without using the appropriate personal protective equipment (PPE).
Travelers to Asian and African countries have the highest risk of being exposed to the virus. Influenza A (H5N1) has recently spread throughout Europe and North America and has been found in some areas of Central and South America.
The following practices are recommended during a trip:
• Avoid high-risk areas such as poultry farms, live animal markets, and areas where poultry may be slaughtered. Be alert to the presence of backyard poultry when visiting friends and relatives.
• Avoid contact with birds (alive or dead), including chickens, ducks and wild birds.
• Avoid surfaces with bird droppings or secretions on them.
• Make sure that all poultry dishes, including eggs, are well cooked (see Health Canada: Meat, poultry, fish and seafood safety).
If you develop symptoms of avian influenza when you are travelling or after you return, see a health care professional to describe any symptoms, your travel history, and if you have had any contact with birds or close contact with a sick person. The health care professional may provide you with additional guidance to follow during your appointment. Wear a mask if fever or respiratory symptoms develop.
What measures should be taken for a suspected H5N1 Avian Influenza case or contact?
Exposed persons, including those who used personal protective equipment (PPE), should monitor their health starting on the first day of exposure and for ten days after the last exposure. Any signs or symptoms of illness should be reported to a physician and the local and state public health department. Signs and symptoms to watch out for include fever or feeling feverish, cough, runny nose, sore throat, headache, muscle aches, eye redness, difficulty breathing, shortness of breath, and diarrhea.
If symptomatic after exposure or have confirmed an infection, isolate away from others and follow measures which help reduce the spread of influenza and other respiratory viruses, including respiratory etiquette (e.g., covering your mouth and nose with a tissue or your elbow when coughing or sneezing), physical distancing, wearing a mask when physical distancing is not possible, regular hand hygiene, improving indoor ventilation (e.g., opening windows), and regularly cleaning and disinfecting of surfaces and objects.