National case definitions: Human infections with avian influenza A(H5N1) virus

Preamble

The epizootic of A(H5N1) that began in late 2021 on the east coast of Canada and quickly spread across North America has led to increased attention to the potential spillover of the virus into humans^{Footnote 1}.

The main public health response goal of emerging respiratory virus surveillance is early detection of any human case in Canada. Subsequently, such virus surveillance informs efforts at containment and/or mitigation of this novel respiratory pathogen. A secondary goal, in the context of the emergence or re-emergence of A(H5N1) outbreaks such as in the 2021-2023 North American epizootic, is to inform risk assessment by growing the evidence base on human infection risk and spectrum of illness, including asymptomatic or atypical presentations. This document outlines surveillance case definitions for Avian Influenza A(H5N1) Virus and provides instructions on reporting to the national level.

Surveillance case definitions are provided here for the purpose of case classification and reporting to the Public Health Agency of Canada. They are based on the current level of epidemiological evidence and uncertainty, as well as the above-noted public health response goals. Note that case definitions are subject to change as new information becomes available. These surveillance case definitions are not intended to replace clinician or public health practitioner judgment in individual patient management, or intended to be used for the purpose of infection control triage.

It should be noted that unusual severe acute respiratory illness (SARI) clusters in community or facility settings (and notably involving health care workers) should be appropriately investigated under the direction of local and provincial health authorities.

Initial diagnostic tests specific for Avian Influenza A(H5N1) can be performed in select laboratories (i.e. provincial public health and hospital-based laboratories). Such cases are considered probable pending confirmation. Jurisdictions without this capability should seek confirmation testing from Canada's National Microbiology Laboratory (NML) before being considered conclusive whereas jurisdictions that have alternative tests (e.g., sequencing or validated polymerase chain reaction [PCR]) may rely on NML or perform their own confirmatory testing. The latter jurisdictions may rely on NML to confirm the first A(H5N1) human cases and then later conduct confirmatory testing on their own. All positive samples must be shared with NML to fulfill their obligations as a National Influenza Centre and Canada's obligations under the International Health Regulations and other agreements. For more information on appropriate specimens or targets for laboratory testing, refer to the Protocol for Microbiological Investigations of Severe Acute Respiratory Infections (SARI).

Provincial/Territorial public health authorities should report confirmed and probable cases of H5N1 nationally within 24 hours of their own notification irrespective of illness severity. For more information on notification mechanisms and case report forms, refer to Emerging respiratory pathogens and Severe Acute Respiratory Infection (SARI) case report form. Persons under investigation (PUI) are not required to be reported nationally.

National surveillance case definitions are provided below - these are subject to change with ongoing monitoring and as understanding of A(H5N1) characteristics and risk assessments evolve.

National Surveillance Case Definitions for Avian Influenza A(H5N1)

Person under investigation (PUI):

• A person meeting the exposure criteria with or without symptoms that are compatible with illness criteria, who is positive for influenza A and for whom subtyping laboratory test results are unknown or pending.

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

Note: Limited data suggest that A(H5N1) can present as a co-infection with other viral as well as bacterial pathogens^{Footnote 2}. The identification of one causal agent should not exclude A(H5N1) where the index of suspicion may be high. In the context of high community circulation of other respiratory pathogens, an individual positive for another viral pathogen (e.g., SARS-CoV-2, seasonal influenza) in the absence of unusual disease does not comprise a situation where suspicion of A(H5N1) infection is high.

Probable Case:

• A person who has influenza A results suggestive of a non-seasonal influenza strain pending confirmatory test results by the NML and/or the provincial/territorial public health laboratory AND
  • meets the exposure criteria, regardless of symptoms, 

    OR

  • has symptoms compatible with illness criteria

Note: A positive non-seasonal influenza A test is appropriate when there is no alternative etiologic hypothesis. For example, an individual who meets the exposure and/or illness criteria and is positive for influenza A and is negative for A(H1) and A(H3) should be included in this definition of a probable case. However, an individual who tests positive for influenza A and an H3 infection is not a probable case.

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

Confirmed Case:

• A person with laboratory confirmation of influenza A(H5N1) infection at Canada's National Microbiology Laboratory (NML).

Note: The NML can confirm detection of the virus using H5N1 specific reverse transcription polymerase chain reaction (RT-PCR) and/or further genetic analysis.

Exposure and Illness Criteria

• Exposure criteria: Exposure within the previous ten (10) days to any of the following: direct or indirect close contact (within 2 metres) to presumptive/confirmed infected birds or other animals (e.g., visiting a live market, touching or handling infected animals, under- or uncooked poultry or egg) close contact (within 2 metres) with a PUI, probable, or confirmed human case, unprotected exposure to biological material (e.g., primary clinical specimens, virus culture isolates) known to contain avian influenza virus in a laboratory setting, or unprotected, direct or close contact (within 2 metres) to contaminated environments.
  • Incubation period for H5N1 has been reported as one to five days, and up to seven days^{Footnote 3}. Longer incubation periods have been suggested^{Footnote 3}. This is considered prolonged compared to typical human influenza viruses (average 1 to 4 days^{Footnote 4}). The available evidence supports exposure criteria based on 10 days 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.
  • Exposure to contaminated environments includes: direct contact with surfaces contaminated with animal parts (e.g., carcasses, internal organs) or feces from A(H5N1) infected animals^{Footnote 5} or settings in which there have been mass animal die offs in the previous six weeks due to A(H5N1)^{Footnote 6Footnote 7}. This period is based on limited evidence from experimental studies^{Footnote 6Footnote 7}. There is insufficient evidence regarding other factors potentially affecting virus survivability, such as temperature, airflow, type of surface material and fallow period.

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 distance considered in defining the sharing of a confined air space may be extended.

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^{Footnote 8}. 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 H5N1 virus infections have occurred and have been reported in the literature^{Footnote 9}. There has been no evidence of sustained person-to-person spread of A(H5N1). In light of the lack of direct human evidence of an infectious period, it is reasonable to consider a typical exposure period for contacts spanning one day prior and through the symptomatic period of the case^{Footnote 10} 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 SARI or ILI. SARI symptoms are fever (over 38 degrees Celsius), and new onset of (or exacerbation of chronic) cough or breathing difficulty and evidence of severe illness progression^{Footnote 6}. ILI is defined as acute onset of respiratory illness with fever and cough and one or more of the following: sore throat, arthralgia, myalgia or prostration, which could be due to influenza virus^{Footnote 11}. In children under 5, gastrointestinal symptoms may also be present. In patients under 5 or 65 and older, fever may not be prominent. If the index of suspicion is high and depending on clinical judgement, individuals with the following additional signs and symptoms may also be considered as meeting illness criteria: rhinorrhea, fatigue, headache, conjunctivitis, shortness of breath or difficulty breathing, pneumonia, diarrhea, respiratory failure, acute respiratory distress syndrome, neurologic symptoms, or multi-organ failure^{Footnote 9}. The variation in spectrum of illness ranges from mild, atypical to severe^{Footnote 9}.

Many infectious diseases present with a spectrum of illness, including mild or asymptomatic infection. Clinician and public health judgment should be used in assessing patients with milder or atypical presentations, where, based on exposure, comorbidity or cluster history, the index of suspicion may be raised.

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