Updated May 22, 2024
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 and updated by NCCID staff. Questions, comments, and suggestions regarding this disease brief are most welcome and can be sent to nccid@manitoba.ca
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Questions Addressed in this debrief:
- What are important characteristics of the H5N1 Avian Influenza A virus?
- What is happening with current outbreaks of H5N1 Avian Influenza A?
- What is the current risk for Canadians from H5N1 Avian Influenza A?
- What measures should be taken for a suspected H5N1 Avian Influenza A case or contact?
What are important characteristics of the H5N1 Avian Influenza A virus?
Cause
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 A is a highly pathogenic avian influenza virus that is easily transmitted between birds. It is a zoonotic disease (a disease that transmits from animals to people), that is less well-adapted to mammals. However, mammalian infections are increasing and mammal to mammal transmission has occurred. There have been reports of possible, limited, human-to-human transmission, but there has been no evidence of ongoing transmission of H5N1 AI A between people.
Close contact with infected birds or heavily contaminated environments like poultry farms and live animal markets increases the risk of transmission to humans. Additionally, exposure to other infected animals, such as wildlife or livestock, such as cattle, may also lead to human cases of H5N1 AI A. Such cross-species transmission events remain rare. The virus is spread by infected birds through their saliva, mucosa, and feces. Humans can become infected if the virus enters the eyes, nose, or mouth, or is inhaled. This occurs if the virus is in the air (in the form of droplets or possibly dust) or if a person touches something contaminated with the virus and then touches their mouth, eyes, or nose.
PHAC: Avian influenza A (H5N1) For health professionals
PHAC: Avian influenza A(H5N1): Prevention and risks
WHO: Influenza (Avian and other zoonotic)
CDC: Current H5N1 Bird Flu Situation in Dairy Cows
JAMA Network: Bird Flu Has Begun to Spread in Mammals – Here’s What’s Important to Know
Signs, Symptoms and Severity
Signs and symptoms of H5N1 AI A in humans have ranged from no symptoms to severe illness which can be fatal. Clinical illness caused by H5N1 AI A 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 1 to 5 days and up to 9 days. According to available human case data, approximately half of the over 900 human cases of H5N1 AI A reported globally since 1997 have resulted in fatalities. However, this case fatality rate of around 52% may be an overestimate, as mild infections can go undetected and under-reported.
Uncomplicated H5N1 AI A virus infection in humans can start with symptoms of:
- Shortness of breath
- Cough
- Headache
- Fever
- Aching muscles
Atypical early symptoms may include:
- Runny nose
- Sore throat
- Diarrhea (in severe cases)
- Fatigue
- Conjunctivitis (red eyes)
- Bleeding gums
In rare cases, the infection may progress quickly to severe respiratory illness, which can include:
- Difficulty breathing
- Acute respiratory distress syndrome
- Pneumonia
- Pulmonary hemorrhage
- Pneumothorax
The infection can also lead to altered mental status change/seizures, multi-organ failure in severe cases, which can include kidney and liver dysfunction and cardiac impairment, and eventually death.
Laboratory studies may show:
- Pancytopenia
Imaging studies may show:
- Lobular or segmental consolidation
- Pulmonary infiltrates (bilateral)
PHAC: Avian influenza A (H5N1) Symptoms and treatment
PHAC: Protocol for Microbiological Investigations of Severe Acute Respiratory Infections (SARI)
Laboratory Diagnosis
A laboratory test is required to diagnose H5N1 AI A. Specimen collection can include nasopharyngeal swab (most common, often done in the first few days of illness), throat swab, sputum, bronchoalveolar lavage, and endotracheal secretions.
For accurate detection of the H5N1 AI A virus, RT-PCR with subtyping for the H5 strain should be the primary diagnostic method employed. Positive samples must be shared with the National Microbiology Laboratory (NML) for confirmatory testing and analysis. Rapid Influenza Diagnostic Tests (RIDTs) 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.
PHAC encourages clinicians and front-line laboratory personnel 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.
PHAC: Avian influenza A (H5N1) Symptoms and treatment
PHAC: Avian influenza A (H5N1) For health professionals
PHAC: Protocol for Microbiological Investigations of Severe Acute Respiratory Infections (SARI)
Treatment
For suspected, probable, or confirmed cases of human infections with the H5N1 AI A virus, antiviral medications should be promptly administered. These agents can provide effective treatment, but their benefits are maximized when initiated within the first 48 hours after symptom onset.
Benefits of antiviral treatment:
- Alleviates influenza symptoms
- Shortens duration of illness
- May prevent severe complications and hospitalizations
Antiviral treatment should not be delayed while waiting for laboratory test results. Patients with severe illness require hospitalization.
Antiviral options for the treatment of H5N1 AI A include:
- Neuraminidase inhibitors: oseltamivir, zanamivir, and peramivir
- Amantadine
- Baloxavir
Oseltamivir, zanamivir, and amantadine are available in Canada. Baloxavir and intravenous peramivir may be accessed through the Special Access Program and approved on a case-by-case basis. The appropriate antiviral should be selected based on the individual patient’s characteristics and clinical presentation.
Considerations
The use of amantadine as a monotherapy for avian influenza is not recommended due to the increased reports of antiviral resistance. The emergence of oseltamivir resistance has also been reported. To address this issue, combination therapy of antivirals with different mechanisms of action may be considered for select cases at risk of antiviral-resistant infection with monotherapy (such as immunocompromised individuals). In addition to antivirals, some cases of H5N1 AI A may require respiratory support. However, there is limited evidence for the benefits of adjunctive therapies in patients with H5N1 AI A, such as corticosteroids, macrolide antibiotics, and passive immune therapy. To date, no clinical trials have measured the outcomes of antiviral use in individuals infected with H5N1 AI A. However, data from animal models and human observational studies suggest there are benefits for morbidity and mortality.
Corticosteroids are not recommended for routine use unless indicated for other reasons, such as asthma. Corticosteroids have been linked to prolonged viral clearance and immunosuppression, which can lead to bacterial or fungal superinfection. Therefore, their use should be carefully evaluated and considered only when necessary.
PHAC: Avian influenza A (H5N1) Symptoms and treatment
PHAC: Avian influenza A (H5N1) For health professionals
Health Canada: Special Access Programs
Epidemiology
Originally endemic in bird populations across Africa and Asia, H5N1 AI A virus has now spread to Europe, the Americas, and even Antarctica. Wild birds serve as the natural reservoirs for avian influenza viruses globally, including in Canada. The wide dispersal range of migratory birds facilitates the transcontinental spread of H5N1 AI A. Since the outbreaks of H5N1 AI A 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. As of May 3, 2024, a total of 889 confirmed human H5N1 AI A infections and 463 deaths were reported to WHO between 2003-2024, most of which were reported between 2003-2019 (861 infections, 455 deaths).
H5N1 AI A viruses belonging to clade 2.3.4.4b have been circulating globally for years. Frequent outbreaks began in North American domestic poultry (both backyard and commercial) and wild bird populations since early May 2022. In March 2024, H5N1 AI A was detected in goats and dairy cows and their milk for the first time in the United States (US). One dairy farm worker was also infected following contact with infected cows. In May 2024, CDC reported the second human case of H5N1 AI A associated with an outbreak in US dairy cows. The first human case of H5N1 AI A in Australia, was travel-associated, acquired in India and reported May 2024. Direct or indirect exposure to infected live or dead poultry or contaminated environments, such as feed, water, or bedding material, 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. It is critical to control the spread of avian influenza viruses in poultry to reduce the risk of human infection.
For the general population in Canada, the likelihood of human infection with H5N1 AI A clade 2.3.4.4b acquired from livestock (e.g., cattle, goats, swine) in the next 3 months is very low due to low level of exposure to infectious virus. The impact on public health would be low, given the small number of human cases reported globally despite frequent high-dose exposure in certain populations, which suggests the virus has limited capacity to infect humans at present.
PHAC: Avian influenza A (H5N1) Prevention and risks
NCCEH: Avian influenza A (H5N1) in dairy farms: An update on public health and food safety concerns
WHO: Influenza at the human-animal interface summary and assessment (3 May 2024)
WHO: Influenza (Avian and other zoonotic)
Australian CDC: Media Release – Human case of bird flu in Victoria
Prevention and Control
The annual seasonal influenza vaccine (“flu shot”) does not provide protection against avian influenza. The risk of H5N1 AI A virus infection is low for the public, but basic preventive measures are advisable to mitigate the transmission of zoonotic diseases:
- Avoid close contact with wild birds and other wild animals. Do not touch, feed, or handle them.
- If contact is unavoidable, wear protective gloves or use a doubled plastic bag. Avoid exposure to blood, body fluids and feces.
- Remove gloves after use and practice thorough handwashing with soap and water. Alternatively, use hand sanitizers containing at least 60% alcohol when soap and water are unavailable.
- Always wash your hands after visiting areas where birds and wildlife reside or nest, such as in parks or zoos
- Supervise children to ensure proper handwashing practices.
- Keep pets away from birds, wildlife, and their feces.
For individuals working with poultry, wild birds, livestock (e.g., cattle, pigs, goats) or other wildlife suspected or confirmed to be infected with H5N1 AI A, the following additional precautions are recommended:
- Wear masks and eye protection to prevent exposure to contaminated dust, feathers, secretions, and feces.
- Wear protective clothing, such as gloves, boots, and coveralls.
- Before cleaning contaminated areas, mist dry areas with low-pressure water to prevent aerosolization of fecal matter, dust, and feathers.
- Change clothing and footwear, and wash hands thoroughly with soap and water before moving on to other activities.
- Follow any additional occupational health guidelines, provided by your occupational health provider.
There is no evidence to suggest that fully cooked wild game meat, organs or wild bird eggs are a source of H5N1 AI A infection for humans. However, precautions should be taken when handling wild birds and some wild mammals, due to potential for avian influenza exposure. Hunters and trappers should take precautions when de-feathering, cleaning and preparing wild game, and follow safe food handling procedures. Thoroughly cooking meat, organs and eggs harvested from wildlife will kill the avian influenza virus and other potential pathogens, such as Salmonella.
Human infections of H5N1 AI 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 AI A), 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.
PHAC: Avian influenza A(H5N1): Prevention and risks
PHAC: Avian influenza A (H5N1) For health professionals
WHO: Influenza (Avian and other zoonotic)
Vaccination
Seasonal influenza vaccines do not offer protection against influenza A (H5N1 AI A). The hemagglutinin (HA) protein of recently detected clade 2.3.4.4b HPAI A (H5N1 AI A) viruses in birds and mammals is nearly identical or, in many samples, identical to an H5 candidate vaccine virus (CVV) produced by the CDC. This vaccine would provide good protection against the clade 2.3.4.4b (H5N1 AI A) viruses circulating in birds. This H5 CVV is already available and has been shared with vaccine manufacturers. However, it is not available in Canada for public use.
Although H5N1 AI A 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.
PHAC: Avian influenza A (H5N1) For health professionals
CDC: Technical Report: Highly Pathogenic Avian Influenza A(H5N1) Viruses
CDC: Making a candidate Vaccine Virus (CVV) for a Highly Pathogenic Avian Influenza (Bird Flu) Virus
What is happening with the current outbreaks of H5N1 Avian Influenza A?
Three confirmed cases of H5N1 AI A infection have been reported in the US, one in Colorado in April 2022, one in Texas in April 2024 and another in Michigan in May 2024. The Canadian Food Inspection Agency (CFIA) is currently responding to cases of highly pathogenic avian influenza (H5N1 AI A) in farmed birds across Canada. In the WHO Summary and risk assessment report for the period of March 29 – May 3, 2024, US, Vietnam and China each reported one confirmed case of H5N1 AI A. There were no confirmed cases of H5N1 AI A infection in humans in Canada during this time. May 2024, Australia reported its first human case of H5N1 AI A. The introduction of avian influenza poses a threat to animal and human health, requiring both sectors to be involved in surveillance and response preparations.
WHO: Influenza at the human-animal interface summary and assessment (3 May 2024)
Avian Influenza A (H5N1) – United States of America
CDC: Technical Report: Highly Pathogenic Avian Influenza A(H5N1) Viruses
Australian CDC: Media Release – Human case of bird flu in Victoria
What is the current risk for Canadians from H5N1 Avian Influenza A?
In early 2014, one case of H5N1 AI A infection in a Canadian resident resulting in mortality was reported after the resident had returned from travel in China. Since this case in 2014, no human infections of HPAI H5 viruses have been identified in Canada (current as of May 22, 2024), and the risk of infection for the general public remains low.
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).
TRAVEL ADVISORY:
Travelers to Asian and African countries have the highest risk of being exposed to the virus. H5N1 AI A 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.
NCCEH: Avian influenza A (H5N1) in dairy farms: An update on public health and food safety concerns https://ncceh.ca/resources/blog/avian-influenza-ah5n1-dairy-farms-update-public-health-and-food-safety-concerns
PHAC: Avian influenza Travel health notices
PHAC: Response to detections of H5N1 highly pathogenic avian influenza (HPAI) in Canada 2021 to 2023
PHAC: Avian influenza A(H5N1): Prevention and risks
PHAC: Avian influenza A (H5N1) For health professionals
Health Canada: Meat, poultry, fish and seafood safety
CFIA: Avian influenza surveillance
What measures should be taken for a suspected H5N1 Avian Influenza A 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 a person is symptomatic after exposure or has a confirmed infection, they should isolate away from others and follow measures to reduce the spread of influenza and other respiratory viruses. These include 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.
PHAC: Avian influenza A (H5N1) Symptoms and treatment
PHAC: Avian influenza A(H5N1): Prevention and risks