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National Interim Case Definition: Avian Influenza A(H7N9) Virus

A. Preamble

The main goal of emerging respiratory virus surveillance is early detection of a case in Canada, and subsequently such virus surveillance informs efforts at containment and/or mitigation of this novel respiratory pathogen. This document outlines surveillance case definitions and provides instructions on reporting to the national level.

While a spectrum of illness is recognized for most infectious diseases, emerging zoonotic pathogens, newly adapting to the human host, are frequently associated with more severe clinical presentation and are more likely to be detected on that basis. Conversely, searching for mild or asymptomatic infections due to an emerging pathogen would likely result in a significant drain on the health care system. Given that it is not possible to test, isolate and/or quarantine all individuals with links to affected areas, the surveillance case definitions focus primarily on severe acute respiratory illness (SARI), while still allowing for clinician and public health judgment in assessing patients with milder or atypical presentations, where, based on contact, comorbidity or cluster history, the index of suspicion may be raised and more aggressive measures taken.

Emerging respiratory pathogens newly adapting to the human host may also demonstrate epidemiologic characteristics atypical for other humanized variants within the same family of viruses. For instance, the incubation period may be prolonged and may further vary based upon viral inoculum and other aspects of the particular agent-host-environment (exposure) context. Transmission characteristics similarly may vary and evolve. As an emerging respiratory virus adapts to the human host, and case investigation becomes more complete, clinical and epidemiologic understanding may change.

Surveillance case definitions are provided here for the purpose of case reporting and notification to the Public Health Agency of Canada. They are based on the current level of epidemiological evidence and uncertainty, and public health response goal. 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 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.

B. Background:

New influenza viruses with pandemic potential typically arise from avian species or swine, but sometimes the animal reservoir seeding new human infections cannot be identified. H7 subtype viruses (i.e. H7N7, H7N3, H7N2) have previously caused a limited number of mild upper respiratory infections in humans, typically in association with recognized poultry outbreaks. The avian influenza A(H7N9) variant, never before identified as a human pathogen, emerged in China during the spring of 2013 causing a greater number of human SARI cases in the shortest period of time than any other avian influenza virus to date, including H5N1. The case fatality has approached 30%.

The avian influenza A(H7N9) virus is a novel influenza A subtype with a complex reassortment of several avian influenza viruses. Although their significance is not yet clear, the virus has multiple genetic signatures suggestive of recent human adaptation and increased virulence. Human infections have been identified, primarily during April 2013, across eight provinces of eastern China plus the municipalities of Beijing and Shanghai, with export of a single case to Taiwan. The WHO’s Global Alert and Response websiteExternal Link maintains the latest updates on the total number of cases. Cases have mostly been sporadic and thought to have been acquired through poultry exposure; however, the animal reservoir has been challenging to identify because H7N9 appears to be of low pathogenicity in birds. Avian influenza A(H7N9) infection in people has been predominantly reported among older adult males, an epidemiologic pattern very distinct from that of H5N1 infections previously detected in China.

Limited scenarios of human-to-human transmission of avian influenza A(H7N9) following close (i.e. household or familial) contact have been reported but sustained person-to-person spread has not yet been observed. Although avian influenza A(H7N9) reporting from China has slowed since May 2013 and the risk to Canadians is currently low, further resurgence and individual case importation cannot be ruled out. Clinicians and public health practitioners should remain alert for that possibility.

Provincial / Territorial public health authorities should report confirmed and probable cases nationally within 24 hours of their own notification. National surveillance case definitions are provided below – these are subject to change with ongoing monitoring and as understanding of H7N9 characteristics and risk evolve.

C. Laboratory Specimen and Testing Considerations

Laboratory confirmation is obtained by detection of viral RNA or virus isolation in tissue culture. Currently, H7N9 is designated a Foreign Animal Disease (FAD) requiring CL 3 or higher laboratory conditions for growth/propagation. Confirmation of diagnosis should be sought from Canada’s National Microbiology Laboratory (NML) before being considered conclusive; such cases may be considered presumptive pending NML confirmation.

Influenza subtyping assays are typically less sensitive than identification assays. As such, it may not be possible to subtype weakly positive influenza A detections. Such “untypeable” events should be individually assessed in consultation with appropriate experts. Confirmatory laboratory tests may take up to 7 days from specimen submission.

Limited evidence suggests that upper airway (nasopharyngeal (NP) or throat) swabs for diagnosis may not be as sensitive as lower respiratory specimens for SARI. If an NP swab tests negative for H7N9, consider retesting using lower respiratory specimens such as sputum, endotracheal aspirate, or bronchoalveolar lavage where relevant and clinically indicated. Sero-conversion may be considered supportive evidence in identifying cases when other laboratory diagnosis is not possible; however, antibody assays for H7N9 are still under development and some caution is required in their interpretation.

Laboratory investigation should be according to local guidance for diagnosis and management of community-acquired pneumonia inclusive of other potentially more likely etiologies. Examples of other etiologies include Streptococcus pneumoniae, Haemophilus influenzae B, Legionella pneumophila, other recognized primary bacterial pneumonias, influenza and other respiratory viruses.

Follow infection prevention and control guidelines when collecting respiratory specimens. For additional information, refer to the Protocol for Microbiological Investigations of Severe Acute Respiratory Infections (SARI).

D. National Surveillance Case Definitions for Avian Influenza A(H7N9)

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.

Probable Case:

  • A person meeting exposure and illness criteria and in whom a laboratory diagnosis of untypeable influenza A is made by a facility equipped with the appropriate influenza subtyping capability OR
  • A person with compatible symptoms who is epidemiologically linked to a confirmed case of H7N9 without specimens available for diagnostic testing.

Confirmed Case:

  • A person with laboratory confirmation of influenza A (H7N9) infection.
    Note: See Section C: Laboratory specimen and testing considerations

E. Exposure and Illness Parameters

1. Exposure criteria: Links within 14 daysFootnote a prior to illness onset to affected areasFootnote b (i.e. residence, travel history) or close contactFootnote c with a confirmed or probable case.

Footnote a
Incubation period for H7N9 has been reported as prolonged (median 6 days; range, 1 to 15 days) among initial cases compared to typical human influenza viruses (average 1-3 days). Allowing for inherent variability and recall error and to establish consistency with other emerging respiratory virus monitoring, exposure history based on the prior 14 days is a reasonable and safe approximation.
Footnote b
Affected areas: defined by identification of animal or human infections due to H7N9 to date in China. As affected areas are subject to change, consult the website of the World Health OrganizationExternal Link for up to date information.
Footnote c

A 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 similarly 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.

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).

2. Illness criteria: While mild presentations with fever and cough, or even asymptomatic cases have been noted following infection with avian influenza H7N9, particularly in children, focus is on the detection of severe acute respiratory illness (SARI). SARI is defined primarily by 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).

Therefore, clinician and public health judgment should be used in assessing patients, 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 Public Health Management of Human Illness Associated with Avian Influenza A(H7N9).

Atypical presentations may occur in the presence of immunosuppression or other comorbidity. Clinician discretion, epidemiologic context and local feasibility should be taken into account, in discussion with local/provincial health authorities. Illness onset is defined by the earliest start of influenza-compatible symptoms associated with the current episode.