Guidance on human health issues related to avian influenza in Canada (HHAI)

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Acronyms

AAFC
Agriculture and Agri-food Canada
AI
Avian influenza
CanNAISS
Canadian Notifiable Avian Influenza Surveillance System
CCOHS
Canadian Centre for Occupational Health and Safety
CFIA
The Canadian Food Inspection Agency
CIHR
Canadian Institutes of Health Research
CPIP
Canadian Pandemic Influenza Preparedness
CVO
Chief Veterinary Officer
CWHC
Canadian Wildlife Health Cooperative
DFO
Fisheries and Oceans Canada
ECCC
Environment and Climate Change Canada
FPT
Federal/provincial/territorial
FADES
Foreign Animal Disease Emergency Support Plan
HAA
Health of Animals Act
HC-BMH
Health Canada – Bureau of Microbial Hazards
HCW
Health care worker
HPAI
Highly pathogenic avian influenza
IHR
International Health Regulations
ISC
Indigenous Services Canada
LPAI
Low pathogenic avian influenza
MTA
Material transfer agreement
NGO
Non-government organisation
NACI
National Advisory Committee on Immunization
NCFAD
National Centre for Foreign Animal Disease
NIC
National Influenza Centre
NML
National Microbiology Laboratory
OIE
Office International des Epizooties
OCAP
Ownership, control, access, and possession
PC
Parks Canada
PEP
Post-exposure prophylaxis
PHA
Public health authority
PAHO
Pan American Health Organization
PHAC
The Public Health Agency of Canada
PHEIC
Public Health Event of International Concern
PHL
Public Health Laboratory
PPE
Personal protective equipment
PSOHP
Public Service Occupational Health Program (Health Canada)
P/T
Provinces/Territories
PUI
Person under investigation
SOP
Standard Operating Procedures
SARA
Species at Risk Act
WHO
World Health Organization
WOAH
World Organisation for Animal Health
US CDC
United States Centers for Disease Control and Prevention

Glossary

Exposure sources:

There is relatively limited public health experience with avian influenza (AI) outbreaks and variability has been observed in the epidemiology of these outbreaks caused by different strains. Therefore, it may be necessary to modify the list of exposure sources of AI virus as the outbreak progresses, more information becomes available, or the situation changes (e.g., if there is evidence of airborne spread of the virus from an avian source or other infected animal(s).

Potential exposure sources include:

Note: For outbreak control purposes, a flock, a site (e.g., farm), or an individual who is ill with a history of exposure to an avian/animal source of virus, might be considered a “potential source of AI virus” on epidemiological grounds in the absence of confirmed infection.

Affected site:

Any site at which:

Contact - avian/animal source:

An individual meeting the criteria for confirmed or potential avian/animal exposure to AI virus (see list above).

Contact - human source:

An individual who has been in close contactFootnote 3 with an individual known to be infected with an AI virus (confirmed case) or with an individual suspected to be infected with an AI virus (person under investigation (PUI) or probable case).

For surveillance purposes:

Outbreak in animals:

Using the World Organisation for Animal Health (WOAH) definition [1] as a guide, an outbreak of AI is the occurrence of one or more cases (an individual bird infected by AI, with or without clinical signs) of the disease or infection in an epidemiological unit or group of birds with a defined epidemiological relationship that share approximately the same likelihood of exposure to the virus. This same likelihood of exposure to the virus may be because they share a common environment (e.g., birds on a farm), or because of common management practices (e.g., sharing equipment or employees). Usually, the epidemiological unit is a flock. However, an epidemiological unit may also refer to groups, such as birds/ poultry belonging to residents of a village, or birds/poultry sharing a communal bird handling facility. The epidemiological relationship may differ among AI strains.

Outbreak in humans:

A human AI outbreak is defined as at least one probable or confirmed case of human influenza A of a known or novel avian sub-type or a cluster of probable or confirmed cases related to the same exposure source.

Personal protective equipment:

Personal protective equipment (PPE) are items worn to provide a barrier to help prevent potential exposure to infectious disease. These items may include the following depending on the situation: gloves, gowns, surgical masks with or without visor attachment, respirators, face shields, and eye protection (e.g., goggles).

Unprotected:

The term unprotected in this document refers to insufficient PPE or PPE not worn.

1.0 Introduction

AI is a contagious viral infection that mainly affects birds but can, on occasion, infect humans and other mammals. Human infections with AI are rare and mostly occur after close contact with infected birds or highly contaminated environments, such as poultry farms, wild birds, or live bird markets. These viruses can cause severe disease in humans and have the potential for ongoing genetic mutation or viral reassortment. This guidance document is set in the Canadian context and is based on the best available scientific evidence and expert opinion. The recommendations within this guidance are intended for use to manage the risk of human exposure when AI is detected in Canada. It is not prescriptive in nature, and it does not include recommendations for specific strains of AI (e.g., H5N1).

The human health risks (actual and potential) associated with AI include:

The purpose of this document is to provide recommendations for public health authorities (PHAs) and other stakeholders involved in the management of actual and potential human health issues related to AI outbreaks. This guidance document should be read in conjunction with relevant provincial/territorial and local legislation, regulations, and policies.

The objective of this document is to provide recommendations aimed at:

Early prevention, monitoring, and control of outbreaks in animals may reduce the risk of human infection. As well, if a working relationship between provincial/territorial health authorities and their respective veterinary counterparts does not exist, a working relationship should be established as part of pandemic preparedness efforts. This would help to potentially minimize delays in reporting a confirmed case of AI in animals (e.g., notification of the first case as well as surveillance efforts of the extent of spread within the jurisdiction) and facilitate any necessary public health action to protect human health.

This document is intended to serve as a reference for the mitigation and management of an outbreak related to the human health concerns of AI. Individuals who are involved in the control of the outbreak in the animal population (e.g. culling of infected flocks or euthanasia of birds, cleaning and disinfection of involved sites) and others who may be exposed such as farm owners, employees and persons in close contact with the birds, as well as individuals who work with or handle potentially infected wild birds and wildlife can present an initial opportunity to increase the possibility of the spread of AI into the human population. It is recommended that there is strict adherence to infection control measures to mitigate the risk of possible human infections. The management of individuals should be based on the virus-specific risk, an individual risk exposure assessment, and consideration of other factors, specific to the situation or individual(s), such as risks for certain population groups, including by sex, age, place of residence (e.g., rural), race, ethnicity, and terms of employment.

2.0 Background

AI is an infectious disease of birds caused by type A influenza viruses. All birds are thought to be susceptible to AI viruses, though the degree to which they are clinically affected can vary by species. AI viruses are designated as highly pathogenic AI (HPAI), or low pathogenic AI (LPAI) based on the molecular characteristics of the virus and the morbidity and mortality in birds. In general, infection with LPAI viruses is associated with predominantly mild illness or asymptomatic infection of affected birds, while HPAI is characterized by sudden onset and severe illness with a high mortality rate. There is no correlation between the pathogenicity of AI viruses in birds and the infectious and pathogenic potential in humans; both HPAI and LPAI viruses have caused mild to severe illness in humans who are infected.

2.1 Avian influenza in the wild bird population

Many AI viruses occur naturally in wild birds and circulate in migratory populations. Wild aquatic birds, particularly Anseriformes (e.g., ducks, swans and geese), are the primary reservoir for AI viruses, can spread the virus along vast migratory flyways throughout the world, and are hosts to the greatest genetic diversity of AI viruses (including 16/18 known HA and 9/11 known NA subtypes). [2] [3] Wild waterfowl are often infected with LPAI and develop very few to no clinical signs of disease. AI viruses circulating in wild birds can be LPAI viruses that then mutate into HPAI viruses once introduced into domestic poultry and then spill back to wild birds or may be HPAI viruses that are introduced directly. Domestic birds may become infected with AI viruses following direct contact with wild birds and possibly other infected wildlife or indirectly through contaminated environments.

HPAI viruses were limited almost exclusively to poultry prior to the late 1990s. Following the emergence of an HPAI A(H5N1) virus in 1996, A/goose/Guangdong/1/1996 (Gs/GD), there have been increasing detections of HPAI viruses in wild birds, causing high mortality events when introduced into domestic poultry. [4] In late 2021, HPAI A(H5N1) was detected in poultry in Canada, likely introduced through migratory wild bird populations from Europe. [5] Since then, A(H5N1) has been detected in wild birds in all provinces and territories (P/T) in Canada and has also been detected in wild birds in the United States and Mexico, Central and South America, in addition to Europe, Asia and Africa. Additional information about the 2021-23 wild bird detections in Canada can be found at the Canadian Wildlife Health Cooperative (CWHC) Avian Influenza website.

2.2 Avian influenza in poultry flocks

Prior to 2021, Canada experienced sporadic outbreaks of AI, typically in a single province or region, with the last detection reported in Ontario in 2016 on a single farm (LPAI A(H5N2)). An LPAI mutation to HPAI was observed during the 2004 outbreak in British Columbia where an LPAI A(H7N3) virus mutated to an HPAI virus within days of the initial outbreak on the index farm. [6] Information about previous outbreaks in Canada can be found here: Previous disease incidents - Canadian Food Inspection Agency (canada.ca) and in Appendix A. Recently, HPAI A(H5Nx) viruses of clade 2.3.4.4b, a descendant of the Gs/GD lineage, have been responsible for three large epizootics during 2016−17, 2020−21, and 2021−23 in Europe. As mentioned above, in late 2021, HPAI A(H5N1) was detected in Canada and since then, A(H5N1) has infected an unprecedented number of poultry farms in nine provinces as well as domestic poultry in the United States, Mexico, and parts of Central and South America, in addition to ongoing outbreaks globally, particularly in Europe. [7] Additional information about the 2021-23 outbreak in poultry in Canada can be found here: Response to detections of H5N1 highly pathogenic avian influenza (HPAI) in Canada 2021 to 2023 - Canadian Food Inspection Agency.

2.3 Avian influenza in mammals

In addition to domestic and wild birds, transmission events of high and low pathogenicity AI have been observed in several mammalian species across the globe. Prior to the current A(H5N1) epizootic, HPAI and LPAI viruses have been reported in wild and domestic mammals, including numerous carnivorous species, as well as marine mammals. Some subtypes of AI have also been transmitted from mammal-to-mammal in some cases, and some viruses have eventually become endemic in swine, canine, and equine populations. [8] [9] [10] [11]

The A(H5N1) virus responsible for the 2021-23 epizootic in North America has been found in multiple mammal species in Canada and the United States, including foxes, skunks, mink, otters, bobcats, opossums, coyotes, bears, dolphins, seals, and domestic mammals (e.g., cats, dog). Additional information about the 2021-23 wild mammal detections in Canada can be found at the CWHC Avian Influenza website. Genetic sequencing indicates the A(H5N1) virus has reassorted with locally circulating North American wild bird AI lineages in some regions of Canada. Genetic sequencing has also identified evidence of mammalian adaptions in some viruses recovered from infected animals. Recent transmissibility and pathogenicity studies with the Eurasian and reassortant strains in the United States and Canada have found evidence of more severe disease in mammals, including evidence of neurotropism and end-organ damage. [12] It is critical to monitor genetic changes in influenza viruses recovered from infected avian and mammalian species, as any changes in the virus that increase severity, enhance antiviral resistance, or indicate mammalian adaptation may increase the risk of human infection. Outbreaks of A(H5N1) in farmed mink in Spain and sea lions in South America with possible mammal-to-mammal transmission have further increased concerns about mammalian adaptation and the need to continue to monitor genetic changes in the virus. [13] [14] [15] [16]

2.4 Human health context

2.4.1 Avian influenza transmission to humans

AI infection in humans can occur as a result of contact with infected poultry infected wild, domestic or pet birds, manure and litter containing high concentrations of the virus, contaminated surfaces, or contact with contaminated vehicles, equipment, clothing, and footwear at involved sites (e.g., infected poultry farms), as well as potentially from uncooked or undercooked poultry products. Handling samples containing the virus in a laboratory setting as well as direct contamination of the mucous membranes by infectious droplets or inhalation of aerosolized viruses are other possible transmission routes. Cases of human infection generally occur following close contact with sick or dead domestic poultry at locations where on-farm biosecurity measures are non-existent or less stringent (e.g., in a live bird market or backyard flocks). Humans have also previously been infected and have experienced a spectrum of illness from both LPAI (e.g., LPAI A(H9N2) or LPAI A(H7N9), causing low and high mortality, respectively) and HPAI viruses. Precautions are therefore warranted regardless of the pathogenicity of the AI virus in bird population. In general, AI infections in humans are rare events and the likelihood of human infection with AI virus is low; however, individuals should remain cautious and adhere to public health measures recommendations (see section 9). A major global human health concern is that outbreaks, particularly in domestic poultry flocks and other high-density populations of animals (e.g., farmed or wild mammals), present an opportunity for ongoing genetic mutation or viral reassortment. Simultaneous co-infection with human and AI viruses in an intermediary host (such as a human or pig) may provide an opportunity for an exchange of genes, one possible outcome being the development of a new influenza virus subtype with pandemic potential (i.e., a novel strain of influenza with the capacity to infect humans and readily transmit from one human to another).

2.4.2 Pandemic phases

According to the World Health Organization (WHO), identification of a novel influenza virus (e.g., AI) strain in a human denotes the beginning of the Alert phase of the continuum of pandemic phases.Footnote 4 The Alert phase calls for increased vigilance and risk assessment of the situation. De-escalation to the Interpandemic phase is possible at this step if the novel influenza virus does not develop into a pandemic strain. However, if global spread of human influenza caused by a new strain is observed, the Pandemic phase begins. This is distinct from the declaration of a Public Health Event of International Concern (PHEIC) or a global pandemic as these declarations lie under the responsibility of the WHO Director-General. [17] According to the WHO, a PHEIC is defined as “an extraordinary event which is determined to constitute a public health risk to other States through the international spread of disease and to potentially require a coordinated international response.” A PHEIC can be a situation that is: serious, sudden, unusual or unexpected; carries implications for public health beyond the affected State’s national border; and may require immediate international action. [18] It is important to note that if Canadian virological, epidemiological, clinical data and surveillance indicators reveal an increased risk within the country, there could be a need for increased public health actions to mitigate and control the risk to the Canadian population, prior to the declaration of either a Pandemic phase or a PHEIC by WHO.

Education of all stakeholders is expected as part of the first response to an outbreak. Ideally this education should be performed in advance, as part of pandemic preparedness activities. Awareness of the potential broader consequences of AI virus outbreaks may facilitate compliance with recommended control measures.

Additional links

3.0 Roles and responsibilities

3.1 One Health approach across shared mandates

Successful response and containment of AI outbreaks are a shared responsibility among government (federal, provincial/territorial, local/municipal, Indigenous), industry, intergovernmental organizations, and academia/non-government organizations, spanning public health, agriculture, and environmental sectors. Recent outbreaks have highlighted the importance in having roles and responsibilities clearly defined to support appropriate, effective, and timely communication and response horizontally across sectors and vertically across levels of government. It is imperative that the many partners have a clear understanding of their roles, and recognition of the interconnection between people, animals, and their shared environments. Achieving optimal health outcomes for all requires working across and between mandates using a “One Health” approach.

Outbreaks of infectious diseases illuminate existing social, economic, and health inequities and have the potential to cause unintended harm or consequences to diverse population groups already experiencing inequities. Regardless of role and responsibility, consider the importance of integrating equity values and principles within decision-making during the management of AI outbreaks. For example, ensure communications are culturally competent, tailored, and accessible, as appropriate.

The following list outlines key departments/organizations and associated key roles. P/T may have existing response frameworks that involve more organizations than those listed below (e.g., Ministry of Labour).

Detailed information on key roles, compiled in a table format, is provided in Appendix B. It can be used as a reference to clarify roles and responsibilities at the outset of any future avian outbreaks.

The roles and responsibilities identified in this protocol are subject to existing federal, provincial/territorial, and municipal legislation, regulations, and agreements. They should be read in conjunction with relevant provincial/territorial and local legislation, regulations and policies.

3.2 Federal roles and responsibilities

Canadian Food Inspection Agency (CFIA): The lead authority for the prevention, detection, response and management of reportable diseases in domestic mammals and poultry in Canada. They are responsible for the administration and enforcement of the federal Health of Animals Act (HAA) and associated regulations. HPAI and low pathogenicity H5 and H7 AI viruses are reportable diseases under the HAA, and consequently, all cases must be reported to the CFIA. CFIA is also the liaison with the World Organisation for Animal Health (WOAH). The CFIA is also home to the National Centre for Foreign Animal Disease (NCFAD), which provides state-of-the-art scientific expertise and technologies for the prevention, detection, control, and reporting of foreign animal diseases zoonotic infections and emerging diseases.

Key roles and responsibilities (as outlined in the HAA):

Environment and Climate Change Canada (ECCC): The identification of risks associated with outbreaks in wildlife and the overall health of wildlife is the collective responsibility of both federal and provincial/territorial departments, ministries, and agencies as well as through academic partnerships (such as CWHC). ECCC is the lead federal organization responsible for the conservation and protection of migratory birds and animals listed under the Species at Risk Act (SARA).

Key roles and responsibilities:

Public Health Agency of Canada (PHAC): The public health system in Canada encourages and supports collaboration between FPT and local health departments and agencies. The overall role of PHAC is to support the prevention and control of infectious diseases in humans through evidence-based recommendations, providing support to assess the risk and reducing the impact of such diseases.

For AI, this is achieved through the following key roles and responsibilities:

The National Microbiology Laboratory (NML) within PHAC is the national public health laboratory for Canada and works with public health partners in Canada and abroad to prevent the spread of infectious diseases. The NML offers highly specialized diagnostic and reference services to detect diseases that are difficult to diagnose, including AI. Furthermore, the NML also provides laboratory-based surveillance through scientific research and collaboration to monitor infectious disease trends and detect and investigate infectious diseases.

Key roles and responsibilities:

Health Canada, Public Service Occupational Health Program (PSOHP): PSOHP is identified as responsible by the Treasury Board of Canada Secretariat (TBS) under the Policy on People management and the Directive on Occupational Health Evaluations to provide occupational health services to Core Public Administration organizations listed in Schedules I and IV of the Financial Administration Act.

Key roles and responsibilities:

Indigenous Services Canada (ISC): ISC works collaboratively with partners to improve access to high quality services for First Nations, Inuit, and Métis. The ISC vision is to support and empower Indigenous Peoples to independently deliver services and address the socio-economic conditions in their communities. In fulfilling the departmental vision and to protect the health of Indigenous Peoples, the First Nations and Inuit Health Branch (FNIHB) provides and/or funds a range of programs and services, including:

Key roles and responsibilities:

Other federal agencies and departments: Other federal agencies and departments that may be involved in a response and their key roles and responsibilities:

3.3 Provincial/territorial/local roles and responsibilities

Local/regional health officials in individual P/T have the mandate under provincial/territorial legislation to investigate and manage human cases, contacts, and outbreaks of diseases of public health significance that occur within their boundaries, including those with a zoonotic source, regardless of the type of animal or food involved. In the event that there is a human case or contact of AI involving a CFIA employee, contractor, or farm employee, the employee/contractor would be required to follow the regulations of the relevant provincial/territorial/local health authority. The health authority may need to coordinate and/or consult with the relevant occupational health and safety (OHS) authority.

Local and regional animal health authorities are responsible for managing animal health risks in their jurisdictions. As highly pathogenic and low pathogenic H5 and H7 viruses are nationally reportable, and in some provincial and territorial jurisdictions are also notifiable or reportable, all suspect or confirmed cases in animals must be reported to the relevant animal health authorities.

3.4 Key non-government organizations providing support

3.5 Federal/provincial/territorial/local shared responsibilities

Additional links

4.0 Principles for information sharing to support public health action

Reporting human cases infected with AI virus to PHAs is a legislated requirement in all P/T, however, reporting of avian or animal influenza infections in animals that may impact human health is only legislated in a small number of provincial jurisdictions, and may vary by subtype of AI and species of animal. Recognizing there are some differences across the P/T, it is important that public health authorities in all affected jurisdictions work closely with the provincial/territorial Department of Agriculture and/or Environment/Natural Resources, and the CFIA, to ensure timely follow up with individuals who were exposed, to protect both the individuals themselves, but also to protect public health more broadly.

Provincial and territorial public health authorities are encouraged to develop working relationships and clear processes (e.g., information sharing agreements) within their respective jurisdictions with their animal health and environment counterparts, and occupational health authorities, in order to facilitate timely, two-way communication to coordinate the response and management of these types of events. Effective communication between human, animal and environment partners allows P/T to be prepared and aware of the AI situation or risks in their jurisdictions.

The route of sharing relevant information to facilitate timely public health follow-up related to domestic poultry and other animal exposures, including personal information, may vary depending on previously agreed upon protocols and information sharing agreements within the P/T (e.g., Memorandum of Understanding (MOU), Foreign Animal Disease Emergency Support Plan (FADES). If agreements are in place, information may be shared directly between CFIA and provincial and territorial Agriculture or Environment/Natural Resources (depending on the jurisdiction), who then share with local/provincial/territorial public health. In the absence of an information sharing agreement, CFIA will release information based on existing provincial/territorial legislation on a case-by-case basis or if the legislative authority for requesting personal information is clear, and/or if it is to protect the public good to share that information. As well, provincial and territorial liaison positions within CFIA regional emergency response structures can be used to provide public health authorities with information about human exposures for follow-up. Information shared between CFIA and the P/T will be informed by existing data sharing agreements and may include data such as premises ID or location identifier, premises address and producer name/contact information, type of animals involved, number of animals, and date of onset of clinical signs in animals, or date of positive sample, as necessary.

Given that CFIA and provincial and territorial animal health authorities are typically the first point of contact with producers and other individuals exposed, they often play a first-response role, and will provide information to the producer/farm employees or other people who have been exposed on behalf of PHAs when a premises or site is suspected or determined to be positive; the information provided would recommend that individuals exposed self-identify/contact a health professional if they have concerns or develop symptoms. Examples of information provided to poultry producers and other exposed individuals can be found in the links at the end of this section.

Acknowledging that the route and timing of information sharing may vary by jurisdiction, examples of best practices that could be adopted to facilitate information sharing within a province or territory to enable timely public health action include the following:

Information sharing is subject to applicable FPT, and municipal legislation, regulations, and agreements governing the sharing of information, including personal information (e.g., privacy, access to information, and common law relating to confidential business information), as well as principles related to data sovereignty when working with Indigenous Peoples, such as ownership, control, access, and possession (OCAP). The partners recognize that information required to investigate, control, and resolve AI outbreaks will be exchanged in confidence and in a timely fashion to facilitate necessary actions, while respecting laws and legislation, and protecting against unauthorized disclosure.

Additional links

5.0 National case definitions

National case definitions allow for common and consistent communication both nationally and internationally. National case definitions are needed to assist with the identification of individuals who are infected and ill, the assessment of human health risks, and the direction of public health surveillance and response activities.

The process for developing specific national case definitions rely on the clinical presentation and laboratory techniques that are associated with identifying the illness. The identified clinical presentation can change as more epidemiologic information becomes available. This may require an update to the case definitions to improve their sensitivity and specificity, and to align with the event response objectives.

National definitions that include categories for a PUI, probable case, and confirmed case are preferred. The first two categories can assist with the investigation and management of potential cases and can be a placeholder should the confirmed case definition be updated to include asymptomatic or atypical infections.

Since the case definitions are intended to be used nationally, their development should be through consensus and in collaboration with the FPT working groups developed to assist with issues surrounding national surveillance.

Case definitions used in the 2004 AI H7N3 outbreak in British Columbia, [20] PHAC’s national case definition for AI A(H7N9) virus (Appendix C [21] and the U.S. CDC case definitions for AI [22] including A(H5), can be adapted for the specific outbreak situation by the P/T involved in the outbreak, in collaboration with the relevant FPT working groups and PHAC as necessary.

6.0 Avian/animal surveillance

Routine surveillance for avian/animal influenza is carried out in Canada and overseen by the CFIA, in conjunction with federal partners, provincial and territorial veterinary services, diagnostic laboratories, veterinary colleges, veterinary and wildlife practitioners, producer organizations, and wildlife interest groups. Chief Veterinary Officers are the key contacts at the provincial level.

Highly pathogenic AI and low pathogenicity H5 and H7 AI viruses are reportable in Canada, under the Health of Animals Act. All suspect cases must be reported to the CFIA. [23] AIs (HPAI and/or LPAI) may also be notifiable or reportable diseases in some provinces/territories and, consequently, all suspect or confirmed cases in animals must also be reported to the relevant P/T animal health authorities. [24]

The CanNAISS is a joint initiative of government, industry, and Canadian farmers to prevent, detect and eradicate the presence of H5 and H7 subtypes of notifiable AI in Canada's domestic poultry flocks. It is one of several domestic and international surveillance initiatives for AI and was developed to meet guidelines from the WOAH. [25] AI detections that are reportable to WOAH are defined as all high pathogenicity AI viruses, irrespective of their subtypes, detected in birds (domestic and wild), and all low pathogenicity viruses, in domestic or captive wild birds, that have proven natural transmission to humans with severe consequences. [26]

Canada currently monitors for AI through:

Since 2005, the CWHC has led the national multi-agency surveillance program for AI viruses that occur in wild bird populations across Canada, in partnership with provincial/territorial governments, CFIA, PHAC and ECCC. [6] [27] The surveillance program involves testing dead birds and a limited number of live birds from wild bird populations, especially waterfowl, through CWHC regional centres/focal points across the country. Sample collection from live or hunter-harvested birds is led by ECCC and sample collection from sick and dead birds is led by CWHC, with strong support from P/T and Indigenous partners, academic institutions, non-government organizations, and the public. The program allows for the collection of data and the communication of results of H5 and H7 virus types that might be circulating in wild birds and is used to inform preparedness and response activities and biosecurity measures to reduce the risk of transmission of AI viruses to domestic poultry and/or humans.

For a summary of Canadian outbreaks in poultry see Appendix A and Previous disease incidents - Canadian Food Inspection Agency (canada.ca), and for a summary of Canadian detections in wild birds, please see the CWHC Avian Influenza website.

Animal influenza surveillance data has also been collected from several other domestic species, such as swine, equine and canine species, as well as several wildlife species, as animal influenzas represent a potential viral reassortment and recombination risk. In Canada, influenza in swine is endemic, with sporadic outbreaks commonly occurring in several Canadian provinces, and is not a nationally reportable disease. Laboratory findings have indicated that the predominant subtypes in recent outbreaks are H1N1, H1N2 and H3N2. [28] Swine influenza viruses can cause illness in humans, and sporadic human cases have been reported in Canada. [29] In Canadian equine specimens, the predominant subtype has been H3N8, which tends to cause a mild respiratory infection, often difficult to distinguish clinically from equine rhinoviruses and herpes viruses. Equine influenza is not known to cause disease in humans and is also not reportable in Canada. Canine influenza is caused by canine-specific strains of H3N8 and H3N2, both of which can cause severe disease in dogs and are considered endemic in dogs in Asia and the United States. [30] In 2017-2018, an outbreak of H3N2 occurred in dogs in Ontario connected to recently imported dogs from Asia. [31] Fortunately, containment measures appear to have been effective for that outbreak, and H3N2 has only been reported in one dog in Ontario since 2018. Canine influenza is not known to cause disease in humans. Any cases of novel or variant strains of influenza in humans, including those potentially caused by canine, equine or swine influenzas, would be reportable to PHAC under Article 6 of the IHR 2005.

As part of pandemic preparedness, it is strongly recommended that each provincial/territorial health authority develops working relationships with their respective animal health counterparts, if they do not already exist. This could help minimize notification delays when avian or animal influenza is detected in their jurisdiction and will help facilitate implementation of any necessary public health measures for the protection of human health in a timely manner. More information can be found in section 4 and a list of Chief Veterinary Officers is provided in Appendix D.

7.0 Human surveillance

PHAC routinely monitors for human illness caused by emerging respiratory pathogens, like AI, and collaborates with international partners for information-sharing purposes. Multiple surveillance networks and systems like FluWatch (Canada's national surveillance system that monitors the spread of influenza and influenza-like illnesses across Canada) or RVDSS (the Respiratory Virus Detection Surveillance System) or the Protocol for Microbiological Investigations of Severe Acute Respiratory Infections (SARI) that are in place would capture human cases of AI in Canada.

Surveillance activities are critical for characterizing and monitoring the impact of the outbreak on human health, guiding public health actions, and providing data necessary for national and international reporting of the event.

7.1 General recommendations

Surveillance activities should include:

  1. Development of an outbreak case definition for the terms (see Appendix C for an example): person under investigation, probable human case, and confirmed human case of AI. Determination of details regarding specific symptoms, incubation period, exposures and locations of concern in addition to laboratory test results that are associated with confirmed cases. The case definition in Appendix C is recommended to be used by the affected province/territory at the time of the outbreak to address the unique characteristics of the outbreak. P/T are strongly encouraged to align with the national case definition.
  2. Dissemination of the outbreak case definitions to all relevant stakeholders including the public health outbreak investigators, employer/operator occupational health and safety authorities responsible for workplaces in their jurisdictions and persons involved in controlling the outbreak (e.g. ECCC or CFIA employees), all other P/T, surveillance working group members, and other stakeholders who might be involved in case detection (e.g. local medical professionals or hospitals, for example those found in section 3).
  3. Development and dissemination of an outbreak reporting questionnaire to public health outbreak investigators, such as: Emerging Respiratory Pathogens and Severe Acute Respiratory Infection (SARI) case report form. The outbreak reporting questionnaire should allow collection of information related to:
    1. the identification of potential human cases and contacts
    2. epidemiological information: case characteristics (e.g., demographics, presence of comorbidity), exposure criteria, contaminated environment, potential contacts, laboratory test result, incubation period, and illness criteria. This could also include information on the use of medical countermeasures (pre/post-exposure prophylaxis, vaccination, etc.)
  4. Consideration of database and reporting tools that will be used to store and summarize the collected data and assist with case/information management.
  5. Identification of potential human cases and contacts and administration of the outbreak questionnaire to collect epidemiological information and implement the appropriate investigation and public health measures. This will involve communication with a designated person(s) at the affected site/farm(s) and enquiring about any contact (e.g., farmers, families, employees, crews, visitors or others who may have had contact with birds, people or material that potentially, or were contaminated with AI contaminated with AI at the affected site/farm). Through this process, follow-up can be initiated and the number of PUI, probable cases, and confirmed cases can be identified. Further follow up and communication will be required for all individuals identified as potential cases and the contacts. This process can also be used to ensure that educational materials, including public health measures recommendations, have been received by the potential cases and contacts and that any questions they may have, are addressed.
  6. Ongoing surveillance for human illness linked to affected sites/farms (see details in section 9.1).
  7. Ongoing timely reporting on any human cases and control measures put in place, through the normal reporting channels (i.e., local public health to provincial/territorial authority to PHAC). As this information will dictate the pandemic phase for the country, it will also be shared with the Pandemic Influenza Committee and WHO. PHAC will also keep provincial/territorial authorities informed of the national epidemiological trends, as well as with any information on the effectiveness of control measures and medical countermeasures, as they become available (contingent upon the completeness of the cases and contacts database).
  8. NotificationFootnote 10 to any P/T that would be receiving persons that are ill and linked to the outbreak (e.g., workers who have come to assist in clean-up or culling activities and who are now symptomatic and returning to their home province/territory) by the affected P/T employer/operator occupational health and safety authority.Footnote 11
  9. Notification of individuals that are asymptomatic linked to the outbreak who are leaving the affected P/T that they should be aware of the possibility of symptom development up to 14 days after last exposure.Footnote 12 Should symptoms develop, they should be instructed to both see a physician and report their symptoms and link to the outbreak to a local PHA. They should also be asked to restrict their activities as a precaution until a diagnosis can be made. (Note: These individuals may also be provided with contact information for public health individuals in the affected P/T and asked to contact them in order to facilitate further follow-up).
  10. An assessment for evidence of human influenza strains currently circulating in or near the affected area(s).
  11. Consideration of any special studies (e.g., serosurveys for evidence of asymptomatic infection) that might require data or laboratory specimen collection during or following the outbreak.

Jurisdictions not involved in the outbreak should ensure that the identification of any individuals with compatible illness within their jurisdiction and with a link to the outbreak, are notified to the provincial and territorial PHAs in the P/T with the outbreak. These individuals should be managed as per the recommendations in this document for management of cases (see section 9.2 for more details).

8.0 Public health risk assessment

Risk assessment is a systematic process for gathering, assessing, and documenting information to assign a level of risk to a specified hazard. [32] The management of individuals exposed to a source of AI virus should be based on the virus-specific risk, an individual exposure assessment, and consideration of other factors specific to the situation or individual. This risk-focused strategy is also suggested for decisions regarding antiviral prophylaxis (see section 11).

8.1 Virus-specific risk

Influenza viruses are characterized into subtypes based on the surface glycoproteins. There are 18 known hemagglutinin subtypes (H1-18) and 11 known neuraminidase sub-types (N1-11) of influenza A viruses. [33] Not all potential combinations are known to exist and of the 18 hemagglutinin subtypes to date only H1, H2, H3, H5, H6, H7, H9, H10, and H11 have been shown to infect humans.

When an AI virus is detected in animals or humans in Canada, a preliminary risk assessment should be carried out by analyzing the existing data (if any) on the occurrence and severity of the disease on humans from the identified hemagglutinin (H) subtype and the specific (H and N) subtype/strain detected. This assessment may draw on risk assessments conducted at the global, WHO regional, or national level in settings where similar detections have been recorded. The information about the case fatality rate of diseases caused by AI in humans is available in the Human Emerging Respiratory Pathogens Bulletin.[34] The availability of information related to the adaptation of the virus to infect and transmit among mammalian species should also be taken into consideration.

In the event of human detection, such an assessment is a requirement under Articles 6 & 7 of the IHR, even if evidence is limited. The H type will likely be the first available laboratory result and many decisions may need to be made based on this preliminary finding, together with initial animal laboratory and clinical data. Provision of sufficiently detailed public health information where possible, including source and type of the risk, is also a requirement under Articles 6 & 7 of the International Health Regulations.

To facilitate a consistent approach to the management of these occurrences from a human health perspective, the AI virus should first be classified based on the following four designations:

This designation, together with the exposure assessment, should be used to guide the management of contacts of a probable or confirmed source of AI virus. It is important to review these decisions and update the risk assessment as more information becomes available. The designation of the virus could change if confirmed (human cases occur during the course of the outbreak or in the case of new virological findings) in which case the risk assessment and recommended management of contacts may also change.

8.2 Exposure risk

Individuals who have exposures falling into more than one risk group should be managed based on their highest risk exposure. Initially, it is expected that those most likely to be exposed would include individuals who are involved in outbreak control (e.g., CFIA), culling of infected flocks or euthanasia of birds, disposal of carcasses, or cleaning of involved sites, as well as individuals living and working on affected sites who have such contact (e.g., farmers, ECCC workers).

High exposure risk groups:

Moderate exposure risk groups:

Low exposure risk groups:

The exposure-risk categories are not limited to the descriptions above. Other situations may apply and should be assessed on a case-by-case basis.

The individual-level risk exposure assessment should be informed by the national and the local risk assessments, as well as the global risk assessment conducted by WHO, which tend to emphasize population risk hazard. The national and local risk assessments aim to inform the public health response and specifically the need for the implementation of any community-based measures in collaboration with animal health authorities (e.g., quarantine, cancellation of live animal events).

8.3 Other considerations

In order to propose target recommendations for contacts of an avian source or human exposures to the AI virus, it is important to consider other factors in addition to the epidemiology of the outbreak. Other factors that would likely influence risk-based recommendations for contacts include:

9.0 Public health measures

The guidance provided in this document is intended for use when AI is detected in animal or human cases in Canada.

Risk communication and the provision of educational materials are public health measures that could be started immediately with key messages focusing on persons at higher risk for AI (see section 8.2 for risk categories) and evolve as the event unfolds. These measures may play an important role in facilitating compliance with other public health actions.

Upon notification of an avian/animal influenza outbreak with a risk of spreading into the human population (recommendations for information sharing are discussed in section 4), it is recommended that PHAs participate in the investigation and implementation of appropriate public health measures to protect human health. Public health measures (often times implemented by the local PHA with the support of the P/T) will largely be informed by the initial findings from the epidemiologic assessment of the outbreak, as well as the relevant provincial/territorial and local legislation, regulations, and policies. Public health measures put in place should be proportionate to the risk in the local community and outbreak setting, balanced against the risk of unintended consequences of the intervention, and responsive to the local circumstances.

9.1 Human contact management in the community with exposure to an animal/avian source

For the management of all contacts who have been exposed, including all exposure-risk levels, to infected animals (wild or domestic) or their environments, PHAs may conduct the following activities (see section 3.3 for more details on provincial/territorial/local roles and responsibilities):

A PHA may consider implementing active monitoring (or screening) of contactsFootnote 13, informed by an individualized risk assessment, based on factors such as:

The frequency (e.g., daily) and method (e.g., in person or by phone) of active monitoring should be determined by the local PHA with consideration given to reasonable resource allocation and severity of illness.

9.2 Human case management in the community following exposure to an animal/avian source

The following measures are recommended for management of PUI/probable/confirmed human AI cases in the community:

10.0 Infection prevention recommendations for individuals involved in animal outbreak situations

The following recommendations have been developed by PHAC, CFIA, ECCC and PSOHP, for application to AI outbreak situations. The recommendations below pertain to infection prevention in the community; infection prevention and control recommendations for healthcare settings are available in Routine Practices and Additional Precautions for Preventing the Transmission of Infection in Healthcare Settings.

Strict adherence to infection prevention and control precautions at affected sites is essential for the control of the AI outbreak and prevention of possible human infection. This information should be conveyed to all those possibly impacted by outbreaks which includes, but is not limited to, employees, volunteers, residents, and visitors of affected sites, as soon as possible when the outbreak is first identified. Affected sites may include, but are not limited to, commercial and small flock poultry farms, backyard flocks, wildlife rehabilitation centres, sanctuaries/zoos, areas with large wildlife die-offs, etc. (see glossary). It is important that messaging be consistent, whether from public health, animal health, or occupational health regulators and authorities, at all levels of government (federal, provincial, regional, local). In this regard, provincial/territorial occupational health regulators and PHAs would be responsible for developing infection control precaution information and recommendations for their respective jurisdictions. Provincial/territorial or local PHAs would also be responsible for conveying this information to farm employees and families, wildlife rehabilitation centres and zoos, provincial or local government employees (e.g., agriculture, natural resources, environment, public health) and the general public, however, this may vary by jurisdiction. PSOHP would be responsible for advising all core federal departments impacted or involved in outbreak response, and CFIA (who is considered outside the core) would be responsible for their employees and others contracted and paid by CFIA within the established outbreak control zones. Appropriate measures to monitor compliance should also be considered in all situations.

10.1 General recommendations/precautions

Contacts of known or potential avian/animal sources of AI are advised to take the following precautions:

10.2 Personal protective equipment (PPE) for contacts of an avian/animal source of virus

Wearing PPE is important to minimize an individual's risk of infection and is strongly recommended for persons who may be exposed to an avian/animal source of AI virus during an animal outbreak response. Individuals involved in the clean-up and/or culling of infected animals and others involved in the outbreak control efforts must follow the PPE requirements as established by CFIA, PHAC, ECCC, and PSOHP.

Recommended equipment includes:

Training in proper techniques of donning, removing, and disposing of PPE without contaminating oneself should be provided by responsible occupational health regulators or authorities.Footnote 16 Hand hygiene must be performed after removing PPE.

Additional links

11.0 Antivirals

Experts (see Appendix E) in antiviral use for influenza, pandemic preparedness, and AI outbreak control and management, make recommendations to PHAC for the application of AI outbreaks and other situations related to AI in Canada.Footnote 17 The recommendations for antiviral use should be reviewed, and modified as necessary, at the time of an AI outbreak with consideration of the epidemiology of the specific AI strain, the scope and impact of the event.

The recommendations in this section are intended to stimulate discussion regarding the potential use of antiviral medications for individuals that could be exposed to, or infected with, AI strains. A risk-benefit approach that considers the risk to the exposed/potentially exposed or person who is infected, the risk to public health, and the risks and benefits of the antiviral medication, in conjunction with available data, informed these recommendations. These high-level recommendations do not constitute medical advice and are not a replacement for individual consultation with a physician who has expertise in influenza treatment and prevention. In particular, when it is recommended that the use of antivirals be “considered,” individuals are encouraged to discuss their specific circumstances and risk factors with a physician to facilitate informed decision-making. Most AI A(H7N9), A(H5N1), and A(H5N6) viruses are susceptible to the neuraminidase inhibitors (oseltamivir, zanamivir, and peramivir) and the polymerase acidic endonuclease inhibitor (baloxavir), but they are often resistant to the adamantanes (amantadine and rimantadine). Adamantanes also have a significantly higher rate of adverse events, including potentially serious adverse events. Therefore, neuraminidase inhibitors are preferentially recommended. Amantadine and rimantadine are not recommended for treatment of AI.

Additional information on antiviral drugs for influenza is available in the Antivirals Annex of the Canadian Pandemic Influenza Plan Preparedness Planning Guidance for the Health Sector, and in manufacturers’ product monographs.Footnote 18

11.1 Background information

Antivirals for the treatment of influenza are most effective if given within 48 hours of symptom onset. Therefore, to facilitate early treatment it is recommended that all individuals with potential exposure to a source of AI monitor themselves for symptoms for the duration of the potential exposure plus an additional 10 days (with or without the use of chemoprophylaxis). The guidance in this section assumes that antiviral medication will be available for the early treatment of AI.

There are three main types of antivirals for influenza: neuraminidase inhibitors, adamantanes (M2 inhibitors), and a recently approved polymerase acidic endonuclease inhibitor (baloxavir marboxil tablets). Based on current availability of product in Canada; existing efficacy data for AI indications; drug resistance potential; and safety and tolerability profiles, only the neuraminidase inhibitors are currently recommended for use for AI indications in Canada.

Neuraminidase promotes the release of virus from infected cells. Neuraminidase inhibitors are drugs that prevent the replication of both type A and B influenza viruses by inhibiting influenza virus neuraminidase. This class of drug has a good safety profile with few side effects and is not likely to be problematic with respect to drug interactions.

Oseltamivir is a neuraminidase inhibitor that is approved for use in Canada for treatment of influenza A and B in persons 1 year of age and older. It is also approved for post-exposure prophylaxis (PEP) against influenza in persons > 1 year of age, following close contact with an infected individual. Oseltamivir is not authorized for use in children less than one year of age in Canada due to an absence of data and is contraindicated in persons with known hypersensitivity to any components of the product. During the 2009 influenza pandemic, oseltamivir was given to over 18 million persons worldwide. Adverse events experienced by patients taking oseltamivir, most commonly gastrointestinal symptoms, were consistent with the drug's known safety profile. Footnote 18

Zanamivir, another neuraminidase inhibitor, could be used as an alternative to oseltamivir in adults and pediatric patients 7 years of age and older for both treatment and prophylaxis. Use is contraindicated in persons with known or suspected hypersensitivity to any component of the product. Zanamivir is provided as an inhaled powder and as such it is not recommended for individuals with underlying airway disease (e.g., asthma, chronic obstructive pulmonary disease) due to the risk of inhalation triggering serious bronchospasm. Availability of zanamivir may be limited in the Canadian market.

The development of resistance to neuraminidase inhibitors is a concern; appropriate surveillance and monitoring should be in place to assess this risk. Five World Health Organization Collaborating Centres for Reference and Research on Influenza Global conducted an analysis of the susceptibility of human influenza viruses to neuraminidase inhibitors on samples collected between May 2018-May 2019 and May 2019-May 2020. Combined phenotypic and NA sequence-based analysis revealed that the global frequency of viruses displaying or with the potential for resistance to neuraminidase inhibitors remained low at 0.5% and 0.6% for the 2018-2019 and 2019-2020 periods, respectively.

Drug susceptibility information for AI viruses is limited. A study in Japan determined the susceptibilities of AI A(H5N1), A(H5N2), A(H5N8), A(H7N7), A(H7N9), A(H9N1), and A(H9N2) viruses, isolated in Japan, to the antivirals approved for use there. [42] Specifically, this study examined antivirals including an M2 inhibitor (amantadine), neuraminidase inhibitors (oseltamivir, peramivir, zanamivir, and laninamivir), and RNA polymerase inhibitors (baloxavir and favipiravir). Both genotypic methods, that detect amino acid substitutions associated with antiviral resistance, and phenotypic methods, that assess phenotypic viral susceptibility to drugs revealed that these AI A viruses were susceptible to neuraminidase and RNA polymerase inhibitors. These results suggest that neuraminidase and RNA polymerase inhibitors, currently approved in Japan, could be a treatment option against these AI A virus infections in humans.

If antiviral resistance is suspected or confirmed during an AI outbreak/event in Canada, consultation with a physician with expertise in this area is highly recommended since both antiviral treatment and prophylaxis protocols may need to be changed.

Since most of the data that was submitted for the approval of neuraminidase inhibitors in Canada was based on influenza strains circulating in humans, as opposed to AI strains, this section contains antiviral recommendations that constitute off-label uses. For example, oseltamivir is only approved for treatment and post-exposure prophylaxis following exposure to a human case. Therefore, individuals who are being prescribed an antiviral in a way that constitutes an off-label use should be informed of that fact as part of the consultation and consent process.

The management of AI outbreaks/events in Canada should, if possible, be used to further the knowledge base regarding the use of antiviral medications under specific circumstances. Ideally, this would include research protocols.

11.2 Antiviral recommendations

The current objective for antiviral use is to minimize the direct risk and impact of zoonotic infection. In conjunction with other measures, antiviral prophylaxis may also reduce the risk of the emergence of a virus with pandemic potential.

11.2.1 Prophylaxis

Indications:

Antiviral use should be guided by an individual risk assessment focusing on the exposure risk and the human illness risk for the specific AI virus (see section 8 for more details). In all circumstances, consultation with medical professional is recommended. If there are no data available on the human illness risk for the strain/subtype of the virus identified, medical professionals may still consider offering the contact antiviral prophylaxis, in particular for those who have had a high-risk exposure and/or pre-existing medical conditions that put them at higher risk for influenza complications.

The specific recommendations for the post-exposure management of contacts, based on the human illness risk and the exposure risks, are summarized in Table 1 below. Additional recommendations for prophylaxis follow the table. In making these recommendations, it is assumed contacts will be self-monitoring for symptoms of AI, and that antivirals will be available for early treatment.

Table 1: Risk-based post-exposure prophylaxis recommendations

(Note: As the situation evolves and additional information becomes available, the recommendations for individuals may change i.e., they may move between the cells in this table)

 
Risk-based Recommendations (Post-exposure) Exposure RiskFootnote *
Low Risk Groups Moderate Risk Groups High Risk Groups
Human
Illness
RiskFootnote *
Subtype has
previously been
identified and is
not known to
have caused
human illness
no prophylaxis no prophylaxis consider offering prophylaxisFootnote **
Subtype is
known to cause
predominantly
mild human
illness
no prophylaxis consider offering prophylaxisFootnote ** offer prophylaxis
Subtype is
known to cause
predominantly
severe human
illness
no prophylaxis offer prophylaxis offer prophylaxis
Footnote 1

See section 8.2 for details regarding these risk categories.

Return to footnote * referrer

Footnote 2

For example, if a pre-existing medical condition puts them at higher risk for severe disease.

Return to footnote ** referrer

Pre-exposure prophylaxis considerations:

Personnel who will be involved in handling sick animals or decontaminating affected environments (including animal disposal) as part of outbreak control efforts (e.g., cullers) are expected to be wearing appropriate PPE and taking appropriate infection prevention and control precautions at all times during these activities, and therefore these individuals should be at low risk of exposure. However, if the AI subtype is known to cause predominantly severe human illness, medical professionals should discuss the option of using antivirals for pre-exposure prophylaxis with these individuals. That is, starting them on a course of antivirals prior to entering a setting where exposure to the virus could occur, as opposed to providing antivirals after an exposure has occurred (i.e., post-exposure prophylaxis).

The consultation with these individuals should take into consideration: individual risk factors (e.g., concerns about a PPE breach, or pre-existing medical conditions that put them at a higher risk of complications from influenza); the need to take the medication daily in order to be optimally protected; the known side effects of the medication; and the fact that this would be an “off label” use. The availability and expected efficacy of post-exposure prophylaxis should also be discussed.

Pre-exposure prophylaxis is not recommended when the AI subtype is known to cause predominantly mild human illness or is not known to have caused human illness. This is based on the low risk of exposure, assuming PPE and other infection prevention and control measures will be in place, ensuring availability of antivirals for post-exposure prophylaxis or early treatment and the low risk of serious illness.

Dosage:

For both post-exposure and pre-exposure prophylaxis, one dose twice daily of oral oseltamivir (or inhaled zanamivir), is recommended instead of the typical antiviral prophylaxis regimen of one dose daily. This is a new recommendation that is based on limited data that support higher prophylaxis dosing in animals for AI A(H5N1) virus infection, [43] and to reduce the potential for development of antiviral resistance while receiving once daily prophylaxis. [44] [45] [46] It is consistent with recommendations from the United States Centre for Disease Control (US CDC); however, it is an off-label use in Canada for these neuraminidase inhibitors to be employed for prophylaxis.

For oseltamivir, the recommended prophylaxis dosing is now the same as the treatment dosing.

Table 2. NEW Recommended oseltamivir dosage for prophylaxis indications:
  Dosage bid (i.e., twice a day)
Adults (≥ 13 years) 75 mg bid
Children weight (> 1 year of age) < 15 kg 30 mg bid
> 15-23 kg 45 mg bid
> 23-40 kg 60 mg bid
> 40 kg 75 mg bid

The dose may need to be adjusted, for example if the individual has renal impairment. More details regarding dose adjustments are available in the respective product monographs.

For post-exposure prophylaxis, a 7-10 day course may be recommended based on the specific exposure risk category (see section 8). Post-exposure prophylaxis should be offered to household and other close contacts of human cases of AI, if the risk assessment suggested that it is prudent.

If a neuraminidase inhibitor is prescribed for pre-exposure prophylaxis, its use should continue for the duration of potential exposure. The maximum duration of time for continuous prophylactic should be eight weeks, this can include intermittent use if, for example, a worker will be in an office setting (i.e., not the potential exposure setting) in between periods of potential exposure. Consideration may be given to extending oseltamivir pre-exposure prophylaxis beyond eight weeks on a case-by-case basis after consultation with a physician who has expertise in influenza treatment and prevention.

11.2.2 Treatment

Indications:

Oseltamivir treatment is recommended for persons one year of age and over, who develop compatible illness following exposure to a source of AI virus.

The effectiveness of neuraminidase inhibitors for treatment of severe disease caused by AI virus infections has not been determined due to a lack of data from randomized clinical trials among patients with novel influenza A virus infections. [47] [48] [49] [50] [51] However, based on data from seasonal (human) influenza A treatment studies, observational data from the treatment of cases that are severely ill and infected with novel/AI viruses, and mechanism of action of neuraminidase inhibitors, treatment of suspect, probable, or confirmed AI with neuraminidase inhibitors is recommended.

To be optimally effective, antiviral treatment should begin no more than two days after the onset of symptoms of influenza. However, in light of evidence showing continuing replication of AI virus beyond 48 hours after onset of symptoms and therefore a potentially beneficial treatment effect with antivirals, consideration should be given to treating individuals presenting at any point during their illness (i.e., not just during the first 48 hours).

All treatment decisions should be made by a physician in consultation with the case. When there is a strong epidemiological link to a source of AI and symptoms are consistent with influenza infection, the decision to treat the suspected case should not be delayed pending laboratory confirmation.

For as-yet untreated cases, therapy may not be of benefit if disease is uncomplicated, fever is absent, and symptoms are improving. Decisions to initiate antiviral treatment should always be based on clinical judgment. Persons who are not treated with antiviral medications should be monitored for progression of illness. [52]

Most AI A(H7N9), A(H5N1), and A(H5N6) viruses are susceptible to the neuraminidase inhibitors (oseltamivir, zanamivir and peramivir) and the polymerase acidic endonuclease inhibitor (baloxavir), but they are often resistant to the adamantanes (amantadine and rimantadine). Adamantanes also have a significantly higher rate of adverse events, including potentially serious adverse events. Therefore, neuraminidase inhibitors are preferentially recommended. Amantadine and rimantadine are not recommended for treatment of AI.

Dosage:

The recommended oral dose of oseltamivir for adults and adolescents 13 years and older is 75 mg twice daily, for 5 days. The treatment dose for children 1-12 years of age is based on their weight and is consistent with the new prophylaxis dosing recommendation, in that it is also two doses daily but for only 5 days. Treatment of infants less than 1 year of age should only be considered after a thorough risk assessment and consultation with a physician as there are limited data on this age group and this would constitute an off-label use.

Longer courses of treatment (e.g., 10 days) may be indicated for cases that are severely ill with AI. AI A(H5N1) and A(H7N9) viruses have been shown to be associated with higher virus levels and longer duration of viral replication (particularly in the lower respiratory tract) in cases who were hospitalized when compared to those with seasonal influenza A or B virus infection. [48] [51] [53] [54] [55]

12.0 Vaccine programs

12.1 Pandemic/avian influenza vaccines

Influenza pandemics are unpredictable but recurring events that occur when a novel influenza virus strain emerges, spreads widely, and causes an outbreak. They have historically occurred every 11-40 years, with the most recent one being H1N1 in 2009. As there are no methods to accurately predict which influenza strain will cause the next pandemic, production of a pandemic influenza vaccine can only begin when a virus with pandemic potential has been identified. Given the current influenza vaccine technologies used by most manufacturers (i.e., egg-based manufacturing technology), the first doses of a pandemic vaccine are expected to only become available within four to six months after a pandemic influenza virus has been identified. [56] The impact of delays in vaccine production were evident during the 2009 H1N1 pandemic when most influenza vaccine delivery occurred after the peak of the pandemic. [57]

Several steps are being taken in the interpandemic period to improve speed of production and vaccine effectiveness. For example, research on potential pandemic vaccines, development of new adjuvants, increased antigen filling capacity, enhanced manufacturing scalability, temporal flexibility, improved methods to make candidate vaccine viruses and reagents’ rapid adoption of new technologies (e.g., recombinant, cell culture, mRNA and plant-based vaccine manufacturing [58]) may help overcome some of the challenges associated with current egg-based vaccine manufacturing processes. For more information refer to the Vaccine annex: Canadian Pandemic Influenza Preparedness: Planning Guidance for the Health Sector. There is an ongoing effort by the Government of Canada to access mRNA technology for use in Canada for pandemic preparedness through a project that is currently under development. [52] Additionally, some countries have stockpiled “pre-pandemic” vaccines based on circulating avian strains considered by WHO to pose a potential risk. [59] Canada does not currently have a stockpile of pre-pandemic AI vaccines, but the Government of Canada maintains a primary domestic contract and two secondary offshore contracts with manufacturers [60] [61] [62] to secure priority access and reserve production capacity to rapidly manufacture and deliver sufficient doses of pandemic influenza vaccine to vaccinate the entire Canadian population during an influenza pandemic. [63] In the event of a Canadian outbreak, access to a vaccine will be facilitated by PHAC through the engagement of pandemic influenza vaccine manufacturers and Health Canada for regulatory review. The National Advisory Committee on Immunization (NACI) will develop expert advice and guidance on the use of pandemic influenza vaccines, including but not limited to prioritization of groups for first vaccines in a shortage situation.

12.2 A(H5N1) vaccine

The World Health Organization (WHO), as part of their Pandemic Influenza Preparedness (PIP) framework, develops and regularly reviews candidate virus vaccines against different H5 clades that can be used by vaccine manufacturers to produce an influenza vaccine. A number of countries, including Canada, have authorized influenza A(H5N1) vaccines, however, there are no widely available vaccines for public use. The decision to use a targeted H5 influenza vaccine would depend on the risk of infection during an A(H5N1) outbreak. The WHO recommends vaccination for first responders to human or animal A(H5N1) outbreaks, and for health care workers who evaluate or manage patients with suspected or confirmed A(H5N1) virus infection in designated referral facilities. More widespread vaccination against A(H5N1) is not recommended in the most recent WHO guidance. [56]

12.3 Seasonal influenza vaccine

Receipt of the seasonal influenza vaccine can potentially reduce the possibility of dual infection with both avian and human influenza viruses in the same person by preventing seasonal influenza virus infection. Preventing dual infections is intended to prevent the possibility of genetic reassortment in an individual infected with both seasonal and AI strains which could theoretically result in a novel pandemic strain. [64] [65] Although there are no real-world data indicating that the seasonal influenza vaccine protects against AI infection or disease severity, several studies have indicated that in some individuals, seasonal influenza vaccination leads to cross-reactive immune responses against AI. [66] [67] [68] [69] [70] [71] [72] [73] These immune responses are more likely driven by the detection of proteins in the hemagglutinin stalk domain that are conserved between seasonal and AI, [67] [68] or non-specific viral components, [66] [70] and they may not be associated with neutralizing functions [69] [71] against AI.

NACI recommends that seasonal influenza vaccine should be offered annually to anyone 6 months of age and older who does not have contraindications to the vaccine. People who are in direct contact with poultry infected with AI during culling operations are identified as a group for whom seasonal influenza vaccination is particularly recommended due to their increased risk of AI infection. This group includes individuals involved in the culling operation as well as others who may be directly exposed to the virus such as supervising veterinarians and inspectors. For more information refer to the Canadian Immunization Guide Chapter on Influenza and Statement on Seasonal Influenza Vaccine for 2022-2023. [74]

When available, seasonal influenza vaccine should be offered to any workers involved in the control of the avian outbreak and ideally should be administered at least two weeks prior to the potential exposure. During the influenza season, contacts of known or potential sources of AI virus who have not received the most recent annual influenza vaccine should be offered this vaccine immediately. [75]

Appendix A: Avian influenza in poultry flocks in Canada

Table 1: Reported outbreaks of low pathogenic avian influenza (LPAI) and highly pathogenic avian influenza (HPAI) in Canadian poultry flocks [6] [76] [77] [78] [79] [80] [81]:

 
Year of detection Strain Province(s) Impact
1966 LPAI H5N1 ON Single farm
1966 HPAI H5N9 ON Single farm
2004 HPAI H7N3 BC 53 farms
2005 LPAI H5N2 BC Single farm
2007 HPAI H7N3 SK Single farm
2009 LPAI H5N2 BC Two farms
2010 LPAI H5N2 MB Single farm
2014 HPAI H5N2 BC 13 farms
2015 HPAI H5N2 ON 3 farms
2016 LPAI H5N2 ON Single farm
2021-2023 HPAI H5N1 (clade 2.3.4.4b) BC, AB, SK, MB, ON, QC, NB, NL, NS 300+ farms, ongoing response

Appendix B: Example of lead agency responsibilities for human health (lead agencies may vary by jurisdiction)

 
Type of Person Potentially Exposed Designated Lead Agency:
Enhanced
Surveillance
Recommendations
Public
Health Recommendations
Clinical
Occupational
Health and Safety Recommendations
AFFECTED FARMS
1. Farmer/producer & farm employees LPHA LPHA P/T OHS/WCB
2. Contractors who provide goods or services to the farm (e.g., feed & manure suppliers) LPHA LPHA P/T OHS/WCB
3. CFIA workers, including inspectors, but also contractors hired by CFIA (e.g., administer CO2 gas, moving bird carcasses, on-site composting) CFIA/LPHA LPHA CFIA
INFECTED WILDLIFE
1. Hunter/trapper LPHA LPHA N/A
2. Employees or volunteers at wildlife rehabilitation facility LPHA LPHA P/T OHS/WCB
3. Provincial Environment/wildlife employees involved in dead bird/animal pick up or sample collection LPHA LPHA P/T OHS/WCB
4. Federal Environment/Parks/Fisheries and Oceans involved in dead bird/animal pick up or sample collection LPHA LPHA Federal Employer/Contractor OHS/PSOHP
LABORATORY
1. Laboratory workers at CFIA Winnipeg laboratory CFIA CFIA CFIA
2. Laboratory workers at Provincial Agriculture laboratory LPHA LPHA P/T OHS/WCB
3. Laboratory technicians and pathologists doing wildlife sampling and testing (e.g., CWHC) LPHA LPHA P/T OHS/WCB/ University OHS

Acronyms: LPHA= Local Public Health Authority, may be P/T, regional or local; CFIA=Canadian Food Inspection Agency; P/T OHS/WCB= Provincial or Territorial Occupational Health and Safety/Workers Compensation Board; PSOHP= Public Service Occupational Health Program

NOTE: The mandate of WCB varies between P/T specifically with respect to their involvement in prevention-focused activities. Another authority might have to assume the prevention functions for workers in P/T where this is not the mandate of WCB.

NOTE: P/T Public Health Authority provides technical support to Local Public Health Authority (LPHA)

NOTE: The Public Health Agency of Canada provides technical support to Canadian Food Inspection Agency (CFIA) and to P/T public health authorities.

Appendix C: National case definition – avian influenza A(H7N9) virus (dated January 25, 2017)

Person under investigation (PUI):

A person meeting exposure and illness criteria.

Note: The surveillance mechanisms and systems for identifying a PUI may vary by jurisdiction according to perceived risk, resources, supporting structures, and other context.

Note: Limited data suggest that H7N9 can present as a co-infection with other viral as well as bacterial pathogens. The identification of one causal agent should not exclude H7N9 where the index of suspicion may be high.

Probable case:

A person epidemiologically linked through close contact to a laboratory-confirmed case and meeting illness criteria but in whom laboratory diagnosis of H7N9 is not available or is indeterminate/unreliable (such as due to specimen quality, viral load or timing).

Note: Efforts to obtain additional specimens to clarify case status may be warranted.

OR

A person meeting exposure and illness criteria and in whom a laboratory screening test for H7N9 was positive but not confirmed by the NML.

Confirmed case:

A person with laboratory confirmation of influenza A(H7N9) infection at Canada's National Microbiology Laboratory (NML).

Note: The NML can confirm detection of the virus using H7N9 specific reverse transcription polymerase chain reaction (RT-PCR) and further genetic analysis.

Exposure and illness criteria

Exposure criteria: Links within ten (10) days prior to illness onset to affected areas (i.e., residence, travel history) or close contact with a confirmed case or a probable case.

Incubation period for H7N9 has been reported as 5 to 6 days (median), with a range from 1 to 15 days. This is considered prolonged compared to typical human influenza viruses (average 1 to 3 days). The available evidence supports exposure criteria based on 10 days prior to illness onset for the purpose of case identification and public health follow up of contacts within Canada. This is considered a reasonable approximation with some loss of surveillance sensitivity balanced against the consideration of local public health capacity to conduct public health investigation and follow-up of cases and contacts.

Affected areas are defined as locations where animal or human infections due to H7N9 have recently been detected. As affected areas are subject to change, consult the website of the World Health Organization for up-to-date information.

Close contact is defined as a person who provided care for the patient, including health care workers, family members or other caregivers, or who had other close physical contact OR who stayed at the same place (e.g. lived with or otherwise had close prolonged contact within two metres) as a probable or confirmed case while the case was ill (beginning 1 day prior to illness onset and continuing until resolution of illness).

Note: Where procedures or presentations are more likely to be associated with virus-laden aerosolization (e.g., CPR, intubation, ventilation, suction, sputum induction, nebulization, bronchoscopy, BiPAP) the time and distance considered in defining the sharing of a confined air space may be extended. For more information refer to the National Interim Infection Prevention and Control Guidance for Acute Care Settings - Avian Influenza A(H7N9).

Note: Current evidence related to seasonal influenza indicates that viral loads in the 24 hours prior to symptom onset are substantially lower than once symptoms begin, peaking with symptom intensity. Effective transmission cannot be directly inferred from viral shedding, but transmission is also anticipated to be greater during the peak symptomatic period, particularly in association with projectile or aerosolizing symptoms such as cough or sneeze. Extension of the relevant exposure period for contacts to include one day prior to symptom onset in the case is thus intended to be a cautious approach for the purpose of emerging pathogen response. Asymptomatic or very mild H7N9 virus infections have occurred, mainly in children but also adults, and have been reported in the literature; however, studies have not conclusively established transmission from asymptomatic individuals. The full duration of the infectious period for influenza A(H7N9) is unknown and may vary with factors such as age, immuno-suppression, other comorbidities or with the intensity/closeness of contact. In that context, it is reasonable to consider a typical exposure period for contacts spanning one day prior and through the symptomatic period of the case while recognizing the need for judgment and adjustment to these guidelines under some scenarios or based on additional local/practical considerations.

Illness criteria: Illness onset is defined by the earliest start of respiratory symptoms associated with the current episode. Focus is on the detection of severe acute respiratory illness (SARI) defined primarily by respiratory symptoms, i.e. fever (over 38 degrees Celsius) AND new onset of (or exacerbation of chronic) cough or breathing difficulty as well as clinical, radiological or histo-pathological evidence of pulmonary parenchymal disease (e.g. pneumonia, pneumonitis, or Acute Respiratory Distress Syndrome [ARDS]), typically associated with the need for hospitalization, intensive care unit monitoring and/or other severity marker (such as death).

Many infectious diseases present with a spectrum of illness, including mild or asymptomatic infection. Atypical H7N9 presentation with absent respiratory symptoms has been documented in the presence of comorbidity, notably immuno-suppression. Therefore, clinician and public health judgment should be used in assessing patients with milder or atypical presentations, where, based on contact, comorbidity or cluster history, the index of suspicion may be raised. Additional information can be found in the Interim Guidance for Containment When Imported Cases With Limited Human-To-Human Transmission Are Suspected/Confirmed In Canada.

Clinician discretion, epidemiologic context and local feasibility should be taken into account in discussion with local/provincial health authorities.

Reference: Government of Canada (2017). National Case Definition: Avian Influenza A(H7N9) Virus:

Government of Canada (2017). National Case Definition: Avian Influenza

Appendix D: Canadian animal health network contacts for Chief Veterinary Officers for animal influenza surveillance

 
Organization Province Member Email
CFIA, CVO of Canada's Office C-CVO Mary Jane Ireland mary-jane.ireland@inspection.gc.ca
Newfoundland and Labrador Department of Fisheries, Forestry and Agriculture NL Beverly Dawe beverlydawe@gov.nl.ca
Prince Edward Island Department of Agriculture PEI Jill Wood jswood@gov.pe.ca
Nova Scotia Department of Agriculture NS Wilma Schenkels dr.wilma.schenkels@novascotia.ca
New Brunswick Department of Agriculture and Rural Development NB Nicole Wanamaker nicole.wanamaker@gnb.ca
Ministère de l'Agriculture, des Pêcheries et de l'Alimentation du Québec (MAPAQ) QC Hélène Trepanier helene.trepanier@mapaq.gouv.qc.ca
Ontario Ministry of Agriculture, Food and Rural Affairs (OMAFRA) ON Greg Worley greg.worley@ontario.ca
Manitoba Agriculture, Food & Rural Initiatives (MAFRI) MB Scott Zaari scott.zaari@gov.mb.ca
Saskatchewan Agriculture SK Stephanie Smith stephanie.smith@gov.sk.ca
Alberta Agriculture and Irrigation AB Keith Lehman keith.lehman@gov.ab.ca
British Columbia Ministry of Agriculture, Fisheries and Food BC Theresa Burns theresa.burns@gov.bc.ca
Northwest Territories Resources, Wildlife & Economic Development NWT Naima Jutha naima_jutha@gov.nt.ca
Yukon YK Mary Vanderkop mary.vanderkop@gov.yk.ca
Nunavut NU Wanda Joy wjoy@gov.nu.ca

Appendix E: Expert antiviral group

 
Name Background Affiliation
Dr. Allison McGeer Infectious Disease Physician Mount Sinai Hospital, Toronto
Dr. Andrea Burry Senior Medical Advisor Health Canada – Public Service Occupational Health Program
Dr. Elizabeth Leung Clinical/Infectious Disease Pharmacist St. Michael's Hospital, Toronto
Dr. Gerald Evans Infectious Disease Physician Association of Medical Microbial and Infectious Disease
Kristen Lewis National Occupational Health and Safety Project Officer Canadian Food Inspection Agency
Dr. Nadine Sicard Public Health Physician Public Health Agency of Canada
Dr. Nelson Lee Infectious Disease Physician University of Toronto
Sonya Tonkovich Canadian Registered Safety Professional Canadian Centre for Occupational Health and Safety

Footnotes

Footnote 1

With the exception of this source (i.e., a human who is infected), all other sources are considered “avian/animal sources”.

Return to footnote 1 referrer

Footnote 2

The “site” in this case would be defined at the time by the authority responsible for the animal health response. It would depend on the specific situation, but the affected site would not include the entire flight paths of wild birds.

Return to footnote 2 referrer

Footnote 3

Close contact: Direct or indirect close contact (within 2 meters) with wild birds, poultry, or other animals with avian influenza A(H5N1) virus infection. Exposures can include, but are not limited to: being in the same closed airspace, touching, handling, culling, or preparation of birds/other animals for consumption (e.g. slaughtering, defeathering, butchering); OR consuming under- or uncooked poultry or egg products; OR direct contact with surfaces contaminated with feces, secretions or animal parts (e.g., carcasses, internal organs) from infected birds/other animals; OR laboratory exposure to the virus; OR visiting a live poultry market with confirmed bird infections or associated with a case of human infection; OR close contact with a probable or confirmed human case.

Return to footnote 3 referrer

Footnote 4

See Figure 2.1 in the WHO’s Pandemic Influenza Risk Management guidance document for a visualization of the continuum of pandemic phases.

Return to footnote 4 referrer

Footnote 5

Each contracted employer is responsible for the occupational health and safety of their own employees, CFIA does not assume the responsibility for onsite contactors. However, CFIA may provide PPE to non-CFIA employed individuals who are conducting work tasks under the oversight of the CFIA at CFIA designated (controlled) work sites. Any case or contact follow-up and management would be the responsibility of local public health.

Return to footnote 5 referrer

Footnote 6

Enhanced surveillance is defined as the increased collection of data above that collected for routine surveillance, and includes identification and monitoring of all exposed individuals as well as laboratory, clinical, demographic, contact and risk factor data, to aid disease control; for example, combining epidemiological and microbiological information to target interventions to prevent the spread of infection. [19] S. e. a. Anderson. "Use and evaluation of national and international surveillance." https://www.healthknowledge.org.uk/public-health-textbook/disease-causation-diagnostic/2g-communicable-disease/surveillance (accessed June 20, 2023).

Return to footnote 6 referrer

Footnote 7

The provincial veterinary service in most P/T operates a veterinary diagnostic laboratory that is used by veterinary practitioners, and may play a significant role in an outbreak, both in testing of specimens and liaising with local producers.

Return to footnote 7 referrer

Footnote 8

The HHAI guidance document is intended to cover all strains/subtypes of AI, therefore, the 21-day follow up period is informed by: 1) evidence of AI virus detection by RT-PCR in human cases extending up to 21 days; 2) transmission dynamics in birds that can shed the virus for prolonged periods (up to several weeks); and 3) the 21-day incubation period for birds as listed in WOAH’s Terrestrial Animal Health Code.

Return to footnote 8 referrer

Footnote 9

This timeline is necessary to impart maximum benefit from antiviral post-exposure prophylaxis, for individuals that are evaluated as being candidates to receive such an intervention, see section 11 for further information.

Return to footnote 9 referrer

Footnote 10

This notification should occur directly between P/T to avoid delays and should include (as permitted by P/T legislation) the individual’s name and contact information as well as the status of the individual with respect to their clinical illness and any required ongoing treatment and monitoring.

Return to footnote 10 referrer

Footnote 11

Similarly, if contacts are being actively managed (e.g., daily active surveillance) as part of the outbreak response, and the monitoring period for the contact has not been completed by the time the individual is leaving the outbreak jurisdiction the affected jurisdiction should be notified.

Return to footnote 11 referrer

Footnote 12

The currently available data on the upper limit of the incubation period for AI is limited and inconsistent. The bulk of evidence points to 10 days as a reasonable upper limit.

Return to footnote 12 referrer

Footnote 13

Active screening refers to asking individuals questions about possible symptoms of infection or exposure.

Return to footnote 13 referrer

Footnote 14

Hand hygiene is the most important measure in preventing the spread of infection after contact with infected or potentially infected animals, contact with contaminated surfaces, or after removing gloves and other PPE. Individuals who are at risk of exposure should be educated on the importance of strict adherence to and proper use of hand hygiene.

Return to footnote 14 referrer

Footnote 15

Fit testing and training are necessary prior to use of an N-95 respirator or other half-face/full-face respirator. These types of respirators are recommended for individuals involved in farm response since the process of culling and/or environmental decontamination (e.g., in affected barns) may cause contaminated materials such as litter or dust, to be suspended in the air, creating a risk potentially similar to an aerosol generating procedure in a hospital setting.

Return to footnote 15 referrer

Footnote 16

Such training must be provided and is the employer's responsibility. A policy and program addressing the use of PPE is also required. Further guidance is available from OHS regulators as well as OHS associations and the CCOHS.

Return to footnote 16 referrer

Footnote 17

It is expected that similar risk-based recommendations would be made if the source of the outbreak was in pigs/swine as opposed to in poultry/avian, however this would need to be re-visited based on the epidemiology of the outbreak and characteristics of the virus.

Return to footnote 17 referrer

Footnote 18

The monographs are available at: https://health-products.canada.ca/dpd-bdpp/index-eng.jsp

Return to footnote 18 referrer

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