Globally, avian influenza A(H5N1) has been detected for several years in domestic birds. Rare zoonotic human cases have been reported, but, as of publishing, without evidence of human-to-human transmission. As of July 2024, less than 1000 A(H5N1) cases in humans have been reported globally since 2003, with a case-fatality rate of 53%. The rate of asymptomatic disease in humans is unknown; however, of the 35 sporadic A(H5N1) human cases reported globally between 2022 and the beginning of July 2024 [including clades: 2.3.4.4b HPAI A(H5N1), 2.3.2.1c HPAI A(H5N1), 2.3.2.1a HPAI A(H5N1)], 8 (23%) were asymptomatic, 11 reported mild illness (31%), 15 were severe or critical illness (43%), and 7 died (20%).

Since 2021, highly pathogenic avian influenza (HPAI) A(H5N1) viruses belonging to clade 2.3.4.4b have been detected worldwide in migrating birds (and other wild species) (see Wildlife dashboard) and domestic birds (see Domestic dashboard), causing large epizootic events with high mortality rates. Avian influenza A (H5N1) clade 2.3.4.4b has also been increasingly reported in an expanded set of mammalian species (marine mammals, wild terrestrial mammals, and domesticated species). Like other countries of the world, Canada has experienced several outbreaks of this virus on farms with domestic birds and sporadic identifications in mammalian species. In the United States, beginning in the spring and early summer of 2024, a number of outbreaks of A(H5N1) were reported on farms with infected domestic birds and cattle in the USA, and several associated human cases have been confirmed (see U.S. Centers for Disease Control and Prevention´s Current situation on A(H5N1) for up-to-date information on the outbreak in the United States). Outbreaks of A(H5N1) had not previously been reported among cattle or in dairy herds.

Unlike cases of A(H5N1) reported globally, the human cases reported in the United States in 2024 with exposure to dairy cattle and domestic birds only reported mild symptoms (e.g., conjunctivitis, fever, chills, coughing, sore throat and runny nose) and all have recovered. There was also limited evidence of mutations associated with human transmission at the time of protocol writing. Of the few human cases that have been reported with the currently circulating clade in the United States (avian influenza A(H5N1) clade 2.3.4.4b), only one marker (PB2 E627K) has been associated with adaptation to mammalian species. Historically, transmission of A(H5N1) from animals to humans has been documented through direct contact with infected birds or contaminated environments, predominantly via exposure to infected birds or their secretions, such as saliva, nasal discharges, and feces, which contain high viral loads. The transmission routes to the human cases working with dairy cattle is unclear but believed to be from cattle to humans through direct or indirect contact with infected animals or their raw or unpasteurized milk. In situations of ongoing contact between infected animals and/or humans, there remains a potential for avian influenza transmission and adaptation to human hosts, which can pose a pandemic risk.

Canadian and international risk assessments (PAHO, FAO-WOAH) have concluded that the risk to humans is currently low but there is an increased risk of spillover events in humans exposed to infected animals, including farm workers (see the Public Health Agency of Canada´s (PHAC) pandemic risk scenario analysis for avian influenza A(H5N1) and the Pan American Health Organization´s public health risk assessment for avian A(H5N1) influenza). A recent update to PHAC´s Pandemic Risk Scenario Analysis suggested that "there was strong agreement that the situation has worsened from last year [2023] due to more mammalian infections creating a significant opportunity for viral adaptation to mammals. Cattle might also be a new mixing vessel with opportunities for reassortment with influenza viruses of mammalian origin, though this is uncertain". Specifically, there is concern that infection of mammals offers opportunities for the virus to reassort, potentially gaining properties that allow it to transmit more efficiently between humans.

Considering knowledge gaps around A(H5N1) transmission, scientists have recommended that enhanced surveillance activities target individuals at higher risk of exposure to inform subsequent risk assessment activities and enhance PHAC´s scientific pandemic preparedness posture. Ongoing existing surveillance is likely to capture severe cases with high-risk exposures that present to public health. However, given the recent increase in mild cases observed in the US, and evidence of missed symptomatic cases on farms in Texas, there is a need to outline a process for sensitive case finding in the event infection is detected on farms in Canada.

A key benefit to the development of the parameters for enhanced human surveillance ahead of the detection of human cases of A(H5N1) in Canada is to generate consensus from a One Health perspective around when an enhanced human health investigation should take place (criteria for implementation), why it should happen (what it will help us to better understand about the virus) and to ensure it is coordinated with on-farm investigations being conducted by other federal, provincial, and territorial (F/P/T) One Health partners. Standardized surveillance protocols already adapted to the Canadian context, also speed up local implementation and promotes ease of roll-up and national interpretability of findings that may be generated from multiple sites across Canada.

Purpose and objectives
This protocol describes a time-limited public health response on Canadian farms to more comprehensively and actively assess A(H5N1) transmission risk to humans from infected animals, investigate likely exposure pathways, and promote early detection of A(H5N1) mutations that could pose a risk to human health (e.g., mutations associated with increased transmissibility, severity, decreased antiviral effectiveness). Evidence generated is expected to inform surveillance case definitions, guidance around prevention of cases (e.g. PPE recommendations), case and contact management, future risk assessments, testing and vaccination policies.

Note: we define farms as establishments primarily engaged in growing crops, raising animals, harvesting timber, harvesting fish and other animals from their natural habitats and providing related support activities. Herein we define farm as those specifically associated with livestock. The term livestock includes: dairy and beef cattle (including feedlots), pigs, poultry and eggs (including hatcheries), turkeys, ducks, geese, sheep, goats, horses and other equines, bison (buffalo), elk (wapiti), deer, llamas and alpacas, rabbits, mink, bees and other animals.

Objectives

To determine whether transmission of A(H5N1) from infected on-farm animals to humans has occurred and to assess whether human-to-human transmission has occurred.
To identify the most likely mode(s) of transmission of A(H5N1) from animals to humans, and between humans.
To collect specimens that could be used for genomic testing to assess epidemiology and viral characteristics relevant to public health (e.g. virulence, transmissibility, antiviral resistance).
To identify the exposure and individual risk factors associated with human infection with A(H5N1).
Summary of approach
We describe time-limited active human case finding as part of an on-farm investigation based on pre-defined criteria. This would involve:

Voluntary testing of everyone exposed to farms associated with recent laboratory confirmed A(H5N1)-infected animals or humans (nasopharyngeal, oropharyngeal and conjunctival swabs and blood samples (serological testing)).
Administration of an epidemiologic questionnaire to all individuals (both cases and contacts) to ascertain exposures and individual risk factors.
The Public Health Agency of Canada recommends enhanced human surveillance and has developed this protocol in consultation with F/P/T One Health partners. Its implementation should be determined based on provincial and territorial public health department needs. This protocol should be interpreted and applied in conjunction with other relevant provincial, territorial (P/T) and municipal legislation and policies. It is not intended to replace local public health response activities, nor the personalized public health advice provided to individuals or groups of individuals, based on clinical judgment and comprehensive risk assessments conducted by public health authorities.