Statement on seasonal influenza vaccine for 2023-2024
Preamble
The National Advisory Committee on Immunization (NACI) is an External Advisory Body that provides the Public Health Agency of Canada (PHAC) with independent, ongoing and timely medical, scientific, and public health advice in response to questions from PHAC relating to immunization.
In addition to burden of disease and vaccine characteristics, PHAC has expanded the mandate of NACI to include the systematic consideration of programmatic factors in developing evidence-based recommendations to facilitate timely decision-making for publicly funded vaccine programs at provincial and territorial levels.
The additional factors to be systematically considered by NACI include: economics, ethics, equity, feasibility, and acceptability. Not all NACI Statements will require in-depth analyses of all programmatic factors. While systematic consideration of programmatic factors will be conducted using evidence-informed tools to identify distinct issues that could impact decision-making for recommendation development, only distinct issues identified as being specific to the vaccine or vaccine-preventable disease will be included.
This statement contains NACI's independent advice and recommendations, which are based upon the best current available scientific knowledge.
This document is being disseminated for information purposes. People administering the vaccine should also be aware of the contents of the relevant product monograph. Recommendations for use and other information set out herein may differ from that set out in the product monographs of the Canadian manufacturers of the vaccines. Manufacturer(s) have sought approval of the vaccines and provided evidence as to its safety and efficacy only when it is used in accordance with the product monographs. NACI members and liaison members conduct themselves within the context of PHAC's Policy on Conflict of Interest, including yearly declaration of potential conflict of interest.
Summary of information contained in the NACI statement
The following highlights key information for immunization providers on seasonal influenza vaccine. Several influenza vaccines are authorized in Canada and the evidence on influenza immunization is continually evolving. NACI will continue to monitor the evidence and update its recommendations as needed. Please refer to the remainder of the statement for details.

# What
- Influenza in humans is a respiratory infection caused primarily by influenza A and B viruses. Seasonal influenza epidemics occur annually in Canada, generally in the late fall and winter months. Prior to the COVID-19 pandemic, influenza had an annual attack rate estimated at 5 to 10% in adults and 20 to 30% in children worldwide.
- Symptoms of influenza can range from mild to severe, and typically come on suddenly. They can include fever, cough, and muscle aches. Other common symptoms include headache, chills, loss of appetite, fatigue, and sore throat. Nausea, vomiting, and diarrhea may also occur, especially in children. Most people will recover within a week to 10 days, but some people are at greater risk of severe complications, such as pneumonia. Influenza infection can also worsen certain chronic conditions, such as heart disease.
- Live attenuated influenza vaccine (LAIV), recombinant influenza vaccine (RIV) and inactivated influenza vaccines (IIV) (which include standard dose  for a list of abbreviations used in this document for the different influenza vaccines.
- The influenza vaccines are safe and well-tolerated. The IIVs and RIV cannot cause influenza illness because they do not contain live virus. The live attenuated influenza vaccines contain weakened viruses.

# Who
NACI makes the following recommendations for individual-level and public health program-level decision making. Individual-level recommendations are intended for people wishing to protect themselves from influenza and for vaccine providers advising individual patients about preventing influenza. Program-level recommendations are intended for provinces and territories responsible for making decisions on publicly funded immunization programs. Individual-level and program-level recommendations may differ, as the important factors to consider when recommending a vaccine for a population (e.g., population demographics, economic considerations) may be different than for an individual.

## Recommendation for individual-level decision making
NACI recommends that influenza vaccine should be offered annually to anyone 6 months of age and older who does not have a contraindication to the vaccine, with focus on the groups for whom influenza vaccination is particularly recommended. These groups include:
- People at high risk of severe disease, influenza-related complications, or hospitalization;
- People capable of transmitting influenza to those at high risk;
- People who provide essential community services; and
- People in direct contact with poultry infected with avian influenza during culling operations.
In infants less than 6 months of age, evidence is lacking to demonstrate that influenza vaccine would be effective. Currently, authorized influenza vaccines are not indicated for use in infants less than 6 months of age. For these reasons, NACI recommends that influenza vaccine should not be offered to infants less than 6 months of age. Since infants less than 6 months of age are at high risk of influenza-related illness, the influenza vaccine should be offered to individuals who are pregnant, breastfeeding, and any household contacts and care providers of young infants.

## Recommendation for public health program-level decision-making
The national goal of the annual influenza immunization programs in Canada is to prevent serious illness caused by influenza and its complications, including death. Programmatic decisions to provide influenza vaccination to target populations as part of publicly funded provincial and territorial programs depend on many factors, such as cost-effectiveness evaluation and other programmatic and operational factors.
- NACI recommends that influenza vaccine should be offered as a priority to the groups for whom influenza vaccination is particularly recommended.

# How
The benefits and risks of influenza vaccination should be discussed prior to vaccination, including the risks of not being immunized.

## Choice of influenza vaccine
A variety of influenza vaccines are authorized for use in Canada, some of which are authorized for use only in specific age groups. Furthermore, not all products will necessarily be made available in all jurisdictions and availability of some products as part of publicly funded provincial and territorial programs may be limited. Therefore, the choice of influenza vaccine has become more complex.

## Dose and route of administration
The dose and route of administration vary by influenza vaccine product:
- Most IIVs are administered as a 0.5 mL intramuscular (IM) injection
- IIV4-HD (Fluzone High-Dose Quadrivalent) is administered as a 0.7 mL IM injection and authorized for adults 65 years of age and older.
- MF59-adjuvanted IIV3-Adj (Fluad) is administered as a 0.5 mL IM injection and authorized for adults 65 years of age and older. A pediatric formulation is also available (Fluad Pediatric), and is administered as a 0.25 mL IM injection for children 6 to 23 months of age.
- RIV4 (SupemtekTM) is administered as a 0.5 mL IM injection and authorized for adults 18 years of age and older.
- LAIV (FluMist Quadrivalent) is administered as 0.2 mL given intranasally (0.1 mL in each nostril) and authorized for individuals 2 to 59 years of age.
See  for information on characteristics of all influenza vaccines expected to be available for use in Canada for the 20232024 influenza season.

## Schedule
NACI recommends that:
- Adults and children 9 years of age and older should receive 1 dose of influenza vaccine each year; and
- Children 6 months to less than 9 years of age who have never received the seasonal influenza vaccine in a previous influenza season should be given 2 doses of influenza vaccine in the current season, with a minimum interval of 4 weeks between doses. Children 6 months to less than 9 years of age who have been vaccinated with one or more doses of seasonal influenza vaccine in any previous season should receive 1 dose of influenza vaccine per season thereafter.

## Contraindications
For all influenza vaccines (IIV, RIV and LAIV), NACI recommends that influenza vaccination should not be given to:
- People who have had an anaphylactic reaction to a specific influenza vaccine, or to any of the components of a specific influenza vaccine, with the exception of egg
	+ Egg allergy is not a contraindication for influenza vaccination, as there is a low risk of adverse events (AEs) associated with the trace amounts of ovalbumin allowed in some influenza vaccines manufactured using eggs. Egg-allergic individuals may be vaccinated against influenza using any age-appropriate product, including LAIV, without prior influenza vaccine skin test and with the full dose, irrespective of a past severe reaction to egg, and in any setting where vaccines are routinely administered. Cell culture-based (IIV4-cc) and recombinant (RIV4) vaccines are egg-free (ovalbumin-free).
	+ As with any vaccine product, all vaccine providers should be prepared to manage possible allergic reactions, including anaphylaxis, and have the necessary equipment to respond to a serious adverse event at all times.
	+ If an individual is found to have an anaphylactic reaction to a component in one influenza vaccine, consideration may be given to offering another influenza vaccine that does not contain the implicated component, in consultation with an allergy specialist. Individuals who have an allergy to substances that are not components of the influenza vaccine are not at increased risk of allergy to influenza vaccine.
- People who have developed Guillain-Barre Syndrome (GBS) within 6 weeks of a previous influenza vaccination, unless another cause was found for the GBS
	+ For these people, the potential risk for a recurrent episode of GBS associated with influenza vaccination must be balanced against the risk of GBS associated with influenza infection itself and the benefits of influenza vaccination.
For LAIV, in addition to the above-mentioned contraindications, NACI also recommends that LAIV should not be given to:
- People with severe asthma (defined as currently on oral or high-dose inhaled glucocorticosteroids or active wheezing) or medically attended wheezing in the 7 days prior to the proposed date of vaccination, due to increased risk of wheezing following administration of LAIV
	+ LAIV is not contraindicated for people with a history of stable asthma or recurrent wheeze which is not active.
- Children less than 24 months of age, due to increased risk of wheezing following administration of LAIV
- Children 2 to 17 years of age currently receiving aspirin or aspirin-containing therapy, because of the association of Reye's syndrome with aspirin and wild-type influenza infection
- Pregnant individuals, because it is a live attenuated vaccine and there is a lack of safety data at this time
	+ LAIV is not contraindicated in breastfeeding (lactating) individuals; however, there are limited data for the use of LAIV in this population.
- People who are immunocompromised due to underlying disease and/or therapy
	+ LAIV is not considered to be contraindicated for children living with stable HIV infection on anti-retroviral therapy (ART; also sometimes referred to as highly active anti-retroviral therapy ) and with adequate immune function.
	+ NACI previously concluded that the quantity of evidence available on the immunogenicity and safety of LAIV in adults with HIV is insufficient to justify a recommendation for the use of LAIV in this group. In addition, NACI considered that most studies found LAIV to have similar or slightly lower efficacy than IIV in adults and consequently recommends IIV for adults with chronic conditions.
LAIV should not be administered until 48 hours after the last dose of an antiviral agent active against influenza (e.g., oseltamivir, zanamivir), and such antiviral agents, unless medically indicated, should not be administered until 2 weeks after receipt of LAIV so that the antiviral agents do not inactivate the replicating vaccine virus.
- If these antiviral agents are administered within this time frame (i.e., from 48 hours pre-vaccination with LAIV to 2 weeks post-vaccination), re-vaccination should take place at least 48 hours after the antivirals are stopped, or a parenteral inactivated or recombinant influenza vaccine could be given at any time.

## Precautions
NACI recommends that:
- Influenza vaccination should usually be postponed in people with serious acute illnesses until their symptoms have abated;
	+ Influenza vaccination should not be delayed because of minor or moderate acute illness, with or without fever. Immunizers should refer to  for additional advice on this issue from PHAC.
	+ More information on vaccinating individuals during acute illness can be found in the Canadian Immunization Guide's section on .
- If significant nasal congestion is present that might impede delivery of LAIV to the nasopharyngeal mucosa, parenteral inactivated or recombinant influenza vaccine can be administered or LAIV can be deferred until resolution of the congestion;
- LAIV recipients should avoid close contact with people with severe immune compromising conditions (e.g., bone marrow transplant recipients requiring isolation) for at least 2 weeks following vaccination, because of the theoretical risk for transmitting a vaccine virus and causing infection; and
- LAIV recipients who are less than 18 years of age should avoid the use of aspirin-containing products for at least 4 weeks after receipt of LAIV because of the association of Reye's syndrome with aspirin-containing products and wild-type influenza infection.

## Concurrent administration with other vaccines
NACI recommends that:
- Administration of COVID-19 vaccines may occur concurrently with (i.e., same day), or at any time before or after seasonal influenza immunization for those aged 6 months and older. Readers should consult the  for updated NACI guidance on the concurrent administration of influenza and COVID-19 vaccines as the number of authorized COVID-19 vaccines and the age groups eligible to receive them expand.
	+ It should be noted that no studies have been conducted on the co-administration of recombinant zoster vaccine (RZV) with adjuvanted or high-dose influenza vaccine. No immune response interference or safety concerns have been demonstrated when RZV is administered concurrently with standard, un-adjuvanted vaccine.
Different injection sites and separate needles and syringes should always be used for concurrent parenteral injections. If multiple injections in the same limb are required, the injection sites should be separated by at least 2.5 cm (1 inch).

# Why
- Vaccination is the most effective way to prevent influenza and its complications.
- Vaccination can help prevent the spread of influenza from person-to-person.
- Although most people will recover fully from influenza infection in 7 to 10 days, influenza can lead to severe disease, complications, or both, including hospitalization and death. Influenza is the most common vaccine preventable disease leading to hospitalization and death in adults.
- Annual vaccination is required because the specific strains in the vaccine are reviewed each year by WHO and are often changed to provide a better match against the viruses expected to circulate in that given year, and because the body's immune response to influenza vaccination may be transient and may not persist beyond a year.
I. Introduction
The National Advisory Committee on Immunization (NACI) provides PHAC with annual recommendations regarding the use of seasonal influenza vaccines, which reflect identified changes in influenza epidemiology, immunization practices and influenza vaccine products authorized and available for use in Canada. This document, the "National Advisory Committee on Immunization (NACI) Statement on Seasonal Influenza Vaccine for 20232024", updates NACI's recommendations regarding the use of seasonal influenza vaccines.

# I.1 New or updated information for 20232024

## Use of seasonal influenza vaccine in the context of coronavirus disease 2019 (COVID-19)

### Guidance on the use of seasonal influenza vaccine in the presence of COVID-19
Seasonal influenza presents an ongoing disease burden in Canada during the fall and winter months. Influenza vaccine is the most effective way to prevent influenza illness and influenza-related complications and is an important component of managing health care system capacity during the influenza season, particularly in the context of ongoing COVID-19 activity.
PHAC, in consultation with NACI and the Canadian Immunization Committee, has developed guidance on the administration of seasonal influenza vaccine to support provincial and territorial vaccine programs and primary care providers during the COVID-19 pandemic:
The guidance on this page is based on currently available scientific evidence and expert opinion and will be updated as necessary throughout the influenza season. This web page should be considered in concert with recommendations regarding the use of seasonal influenza vaccines provided in this NACI Statement*.*

### Guidance on concurrent administration of influenza and COVID-19 vaccines
NACI guidance outlines that administration of COVID-19 vaccines may occur at the same time as, or at any time before or after influenza immunization (including all parenteral or intranasal seasonal influenza vaccines) for those aged 6 months of age and older.
Readers should consult the  for updated NACI guidance and further information on concurrent administration of COVID-19 vaccines with influenza vaccines and across all eligible age groups.

## Updated recommendations on the use of mammalian cell culture-based quadrivalent influenza vaccine (IIV4-cc)
Flucelvax Quad (IIV4-cc) is a standard dose mammalian cell culture-based quadrivalent inactivated seasonal influenza vaccine that was first authorized for use in Canada in adults and children 9 years of age and older on November 22, 2019 with authorization extended to children 2 years of age and older on March 8, 2021. Recommendations and supporting evidence on the use of Flucelvax Quad in adults and children 9 years of age and older can be found in the  and were also incorporated into the Statement on Seasonal Influenza Vaccine for 20212022. Recommendations and supporting evidence on the use of Flucelvax Quad in adults and children 2 years of age and older were incorporated into the .
On March 8, 2022, Health Canada approved an expanded age indication for the use of Flucelvax Quad in children down to 6 months of age and older. Based on a review of Health Canada assessments of clinical trial evidence submitted by the manufacturer in support of the age indication extension, NACI has concluded that Flucelvax Quad is safe and has non-inferior immunogenicity compared to standard quadrivalent inactivated influenza vaccines. Therefore,
NACI recommends that Flucelvax Quad may be considered among the quadrivalent influenza vaccines offered to adults and children 6 months of age and older. (Discretionary NACI recommendation).

## Updated recommendations on the use of egg-based quadrivalent influenza vaccine (IIV4-SD)
Influvac Tetra (IIV4-SD) is a split virus standard quadrivalent inactivated influenza vaccine that was first authorized for use in Canada in adults on March 1, 2019 and subsequently in children 3 years of age and older on February 20, 2020. Recommendations and supporting evidence on the use of Influvac Tetra in adults and children 3 years of age and older were incorporated into the 
On November 30, 2021, Health Canada approved an expanded age indication for the use of Influvac Tetra in children 6 months of age and older. Based on a review of Health Canada assessments of clinical trial evidence submitted by the manufacturer in support of the age indication extension, NACI has concluded that Influvac Tetra appears to be safe and well-tolerated (relative to the control non-influenza vaccines) based on direct evidence in children 6 to 35 months of age. However, there is currently insufficient evidence that Influvac Tetra is effective and elicits a protective immune response against seasonal influenza in children 6 to 35 months of age. Therefore:
NACI recommends that Influvac Tetra may be considered among the standard dose inactivated quadrivalent influenza vaccines offered to individuals 3 years of age and older. (Discretionary NACI recommendation)
At this time, NACI concludes that there is insufficient evidence for recommending vaccination with Influvac Tetra in children younger than 3 years of age. (Discretionary NACI recommendation).
NACI will continue to monitor the evidence as it emerges, and update recommendations as needed.

## Standard-dose trivalent inactivated influenza vaccine (IIV3-SD) authorization and availability
All standard dose, egg-based inactivated influenza vaccines authorized and available in Canada for the 202324 season are expected to be quadrivalent. There are no trivalent formulations (IIV3-SD) authorized (discontinued post-market) or available, but data that involve these vaccines continue to be included for reference.

## Updated presentation of the statement
The presentation of this document has been updated from previous seasons' statements to improve readability and access to information. The content in some sections has been reduced in length, while maintaining a focus on key information required for decision making. Links to other published NACI documents containing the more detailed content removed from the current statement have been integrated.
For a summary of clinical information on seasonal influenza vaccine administration for vaccine providers, please refer to the new 

# I.2 Background
The  are typically available in February of each year for the upcoming season in the Northern Hemisphere. The WHO recommends that three influenza strains be included in the trivalent seasonal influenza vaccine: one influenza A(H1N1), one influenza A(H3N2), and one influenza B. Quadrivalent seasonal influenza vaccines should contain the three strains recommended for the trivalent vaccine, as well as an influenza B virus from the lineage that is not included in the trivalent vaccine.
Health care providers in Canada should offer the seasonal influenza vaccine as soon as feasible after it becomes available and is delivered in the fall, since seasonal influenza activity may start as early as October in the Northern Hemisphere. Decisions regarding the precise timing of vaccination in a given setting or geographic area should be made according to local epidemiologic factors (influenza activity, timing, and intensity), opportune moments for vaccination, as well as programmatic considerations. Further advice regarding the timing of influenza vaccination programs may be obtained through consultation with local public health agencies.
Although vaccination before the onset of the influenza season is strongly preferred, influenza vaccine may still be administered up until the end of the season. Delayed administration may result in lost opportunities to prevent infection from exposures that occur prior to vaccination; therefore, individuals seeking or considering vaccination should be informed that vaccine administered during an influenza outbreak may not provide optimal protection. Vaccine providers should use every opportunity to administer influenza vaccine to individuals at risk who have not already been vaccinated during the current season, even after influenza activity has been documented in the community.
Every year, individuals with influenza and influenza-related complications increase the pressures on the healthcare system in the fall and winter months. Particularly given the added burden on the healthcare system during the COVID-19 pandemic, effective prevention of influenza by vaccination is a critical tool to mitigate on-going health system stress.
II. Methods
Details regarding NACI's evidence-based process for developing a statement are outlined in .
In brief, the broad stages in the preparation of this NACI advisory committee statement included:
- Knowledge synthesis
- Synthesis of the body of evidence of benefits and harms, considering the quality of the synthesized evidence and magnitude and certainty of effects observed across the studies
- Translation of evidence into recommendations
Annual influenza vaccine recommendations are developed by the Influenza Working Group (IWG) for consideration by NACI. Recommendation development includes review of a variety of issues including the burden of influenza illness and the target populations for vaccination; safety, immunogenicity, efficacy, and effectiveness of influenza vaccines; vaccine schedules. In addition, PHAC has expanded the mandate of NACI to include the consideration of programmatic factors in developing their recommendations to facilitate timely decision-making for publicly funded vaccine programs at provincial and territorial levels. These programmatic factors include cost-effectiveness, as well as ethics, equity, feasibility, and acceptability (EEFA). NACI uses a published, peer-reviewed framework and evidence-informed tools to ensure that issues related to EEFA are systematically assessed and integrated into its guidance. The NACI Secretariat applied this framework with accompanying evidence-informed tools (Ethics Integrated Filters, Equity Matrix, Feasibility Matrix, Acceptability Matrix) to systematically consider these programmatic factors for the development of clear, comprehensive, appropriate recommendations for timely, transparent decision-making. For details on the development and application of NACI's EEFA Framework and evidence-informed tools, please see .
The annual update of the *NACI Statement on Seasonal Influenza Vaccine- led by the NACI Influenza Working Group (IWG) involves a thorough review and evaluation of the literature as well as discussion and debate at the scientific and clinical practice levels. In the preparation of the 20232024 seasonal influenza vaccine recommendations, NACI's IWG identified the need for evidence reviews for new topics, and then reviewed and analyzed the available evidence, and proposed new or updated recommendations according to the NACI evidence-based process for developing recommendations. For the 20232024 influenza season, the NACI IWG reviewed evidence and developed new recommendations regarding the use of two vaccines with changes in authorization (expanded use in individuals six months of age and older): 1) Influvac Tetra, an egg-based, quadrivalent inactivated influenza vaccine (IIV4-SD) and 2) Flucelvax Quad, a mammalian cell culture-based, inactivated seasonal influenza vaccine (IIV4-cc). The NACI IWG reviewed and analyzed the available pre-licensure clinical trial data and Health Canada's Clinical Review Reports for these two vaccines. On October 3rd, 2022, the available evidence and the new recommendations proposed by the IWG were presented for consideration and approval by NACI. Following a thorough review of the evidence, the committee voted on specific recommendations. The description of relevant considerations, rationale for specific decisions, and identified knowledge gaps are described in this statement.
III. Epidemiology

# Disease description
Influenza is a respiratory illness caused by the influenza A and B viruses in humans and can cause mild to severe illness, including hospitalization or death. Certain populations, such as young children, older adults, and those with chronic health conditions, are at higher risk for serious influenza complications such as viral pneumonia, secondary bacterial pneumonia, and worsening of underlying medical conditions.

# Infectious agent
There are two main types of influenza virus that cause seasonal epidemics in humans: A and B. Influenza A viruses are classified into subtypes based on two surface proteins: hemagglutinin (HA) and neuraminidase (NA). Three subtypes of HA (H1, H2, and H3) and two subtypes of NA (N1 and N2) are recognized among influenza A viruses as having caused widespread human disease over the past decades. Immunity to the HA and NA proteins reduces the likelihood of infection and together with immunity to the internal viral proteins, lessens the severity of disease if infection occurs.
Influenza B viruses have evolved into two antigenically distinct lineages since the mid-1980s, represented by B/Yamagata/16/88-like and B/Victoria/2/87-like viruses. Viruses from both the B/Yamagata and B/Victoria lineages have contributed variably to influenza illness each year. Since the onset of the COVID-19 pandemic, a reduction in seasonal influenza virus diversity has been observed globally. In particular, an absence of B/Yamagata detections has been noted.
Over time, antigenic variation (antigenic drift) of strains occurs within an influenza A subtype or a B lineage. The possibility of antigenic drift, which may occur in one or more influenza virus strains, requires the formulation of seasonal influenza vaccines be re-evaluated annually, with one or more vaccine strains changing in most seasons.

# Transmission
Influenza is primarily transmitted by aerosols and droplets spread through coughing or sneezing, and through direct or indirect contact with respiratory secretions.
The incubation period of seasonal influenza is usually about 2 days but can range from 1 to 4 days. Adults may be able to spread influenza to others from 1 day before symptom onset to approximately 5 days after symptoms start. Children and people with weakened immune systems may be infectious longer.

# Risk factors
The people at greatest risk of influenza-related complications are adults and children with chronic health conditions (see ), residents of nursing homes and other chronic care facilities, adults 65 years of age and older, children 0 to 59 months of age, pregnant individuals, and Indigenous peoples.

# Seasonal and temporal patterns
Influenza activity in Canada is usually low in the late spring and summer, begins to increase over the fall, and peaks in the winter months. Depending on the year, one or more peaks may occur as early as the fall and into the spring. Influenza season in Canada usually begins in December and lasts 12 to 16 weeks but can start as early as October or as late as February, and last for as long as 20 weeks. Although one strain often predominates, more than one influenza strain typically circulates each season.

# Spectrum of clinical illness
Classically, symptoms of influenza include the sudden onset of fever, cough, and muscle aches. Other common symptoms include headache, chills, loss of appetite, fatigue, and sore throat. Nausea, vomiting, and diarrhea may also occur, especially in children. However, influenza can cause a range of symptoms, from asymptomatic infection through mild acute respiratory illness (a "cold") to severe influenza pneumonia. Most people will recover within a week or 10 days. More rarely, central nervous system manifestations, acute myositis, myocarditis, or pericarditis have been described. In addition, complications including pneumonia, respiratory failure, cardiovascular complications, or worsening of underlying chronic medical conditions may occur. Influenza is also associated with a significantly increased risk of myocardial infarction and stroke in the 7 to 14 days after infection, and with Guillain-Barre syndrome with onset 1 to 6 weeks after infection.

# Disease incidence

## Global
Before the COVID-19 pandemic, worldwide annual epidemics resulted in approximately one billion cases of influenza, three to five million cases of severe illness, and 290,000 to 650,000 deaths. The global annual attack rate is estimated to be 5 to 10% in adults and 20 to 30% in children. Global influenza circulation was at a historical low during the 2020-2021 influenza season, when public health measures (e.g., masking, social distancing) effectively suppressed seasonal influenza activity. During the 2021-2022 Northern Hemisphere season, influenza activity returned to varying degrees in different jurisdictions. During the 2022 Southern Hemisphere season, activity appeared to return to a pre-pandemic level, although incomplete data for the season, changes in testing associated with the pandemic, and the substantial inter-season variability of influenza activity make it difficult to make definitive conclusions.
For current international influenza activity information, refer to WHO's .

## National
Together, influenza and pneumonia are ranked among the top 10 leading causes of death in Canada. Nationally, influenza has been estimated to cause approximately 12,200 hospitalizations and approximately 3,500 deaths annually. The FluWatch program is Canada's national surveillance system, which monitors the spread of influenza and influenza-like illnesses (ILI) continually throughout the year. In the five seasons prior to the COVID-19 pandemic (20142015 to 2018-2019 season), an average of 40,000 laboratory-confirmed cases of influenza were reported to FluWatch each year. However, most influenza infections are not laboratory-confirmed, so the number of cases reported to FluWatch is a significant underestimate of the true number of infections.
The burden of influenza-associated illness and death varies every year, depending on various factors such as the type of circulating viruses in the season and the populations affected. Notably, Canada's 2020-2021 seasonal influenza activity did not reach seasonal threshold and was at a historical low in the context of the public health measures that were implemented to reduce COVID-19 transmission. Only 69 confirmed cases of influenza were identified during the 2020-2021 season, whereas over 50,000 laboratory confirmed cases are reported on average in a typical influenza season. During the 2021-2022 season, influenza circulation in Canada reached the national seasonal threshold that signals the start of seasonal influenza activity for the first time since the spring of 2020. The 2021-2022 influenza epidemic onset was in April 2022, which is an unusually late start to the influenza season. Although the potential impact of upcoming influenza seasons in the context of COVID-19 is unknown, future influenza outbreaks may be characterized by higher infection rates and severity. Influenza infection susceptibility may increase due to low immunity in the population given the extended periods of decreased influenza exposure and infection caused by the implementation of COVID-19-related public health measures. Moreover, disease severity may be exacerbated due to the co-circulation and simultaneous infection of COVID-19 and influenza viruses. Additionally, the resurgence of seasonal influenza may not follow usual seasonal patterns. Information about current influenza activity can be found on the . It should be noted that the incidence of influenza is often underreported since the illness may be confused with other viral illnesses and many people with ILI do not seek medical care or have viral diagnostic testing done.
IV. Seasonal influenza vaccines

# IV.1 Vaccine products authorized for use in Canada
The following sections describe the influenza vaccine products that are authorized for use in Canada for the 20232024 season. All influenza vaccines available in Canada have been authorized by Health Canada. However, not all products authorized for use are available in the marketplace. The vaccine manufacturers determine whether they will make any or all of their products available in each market. Provincial and territorial health authorities then determine which of the products available for purchase will be used in their respective publicly funded influenza immunization programs and for which population groups. Not all products will be made available in all jurisdictions and availability of some products may be limited. Officials in individual provinces and territories should be consulted regarding the products available in individual jurisdictions.
The antigenic characteristics of circulating influenza virus strains provide the basis for selecting the strains included in each year's vaccine. Vaccine selection by the WHO generally occurs in February for the fall's Northern Hemisphere influenza season to allow time for the vaccine manufacturers to produce the required quantity of vaccine. All manufacturers that distribute influenza vaccine products in Canada confirm to Health Canada that the vaccines to be marketed in Canada for the upcoming influenza season contain the WHO's recommended antigenic strains for the Northern Hemisphere. Vaccine producers may use antigenically equivalent strains because of their growth properties. The strains recommended for egg-based products may differ somewhat from the strains chosen for cell culture-based products to account for differences in the production platforms.
There are three categories of influenza vaccine authorized for use in Canada: IIV, RIV, and LAIV. Trivalent (3-strain) vaccines contain one A(H1N1) strain, one A(H3N2) strain, and one influenza B strain from one of the two lineages. Quadrivalent (4-strain) vaccines contain the strains in the trivalent vaccine plus an influenza B strain from the other lineage. Most influenza vaccines currently authorized for use in Canada are made from influenza viruses grown in chicken eggs. However, there are two exceptions. The influenza viruses used to produce Flucelvax Quad are propagated in a mammalian cell line (Madin-Darby Canine Kidney  cells), while the Supemtek vaccine technology uses recombinant HA produced in a proprietary insect cell line using a baculovirus vector for protein expression.
A summary of the characteristics of influenza vaccines available in Canada during the 20232024 influenza season can be found in . For complete prescribing information, readers should consult the product monographs available through Health Canada's .
Should additional vaccine preparations become available for use in Canada after the release of this statement and prior to the 2023-24 influenza vaccine season, NACI will communicate relevant information regarding the new vaccine preparations if required.

## Inactivated influenza vaccine (IIV)
IIVs contain standardized amounts of the HA protein from representative seed strains of the two human influenza A subtypes (H3N2 and H1N1) and either one (for trivalent vaccines) or both (for quadrivalent vaccines) of the two influenza B lineages (Yamagata and Victoria). IIVs currently authorized for use in Canada are a mix of split virus and subunit vaccines, both consisting of disrupted virus particles. In split virus vaccines, the virus has been disrupted by a detergent. In subunit vaccines, HA and NA have been further purified by removal of other viral components. The amount of neuraminidase (NA) in the vaccines is not standardized and not reported. HA-based serum antibody produced to one influenza A subtype provides no protection against strains belonging to another subtype. The potential for trivalent vaccine to stimulate antibody protection across B lineages requires further evaluation and may be dependent upon factors such as age and prior antigenic experience with the two B lineages   .
All IIVs currently available in Canada are produced in eggs, except for Flucelvax Quad (IIV4-cc), which is a mammalian cell culture-based quadrivalent inactivated, subunit influenza vaccine that is prepared from viruses propagated in mammalian cell lines  adapted to grow freely in suspension in culture medium. The production of IIV4-cc does not depend on egg supply as it does not require egg-grown candidate vaccine viruses.
The IIVs available in Canada are in a standard dose formulation or in a formulation designed to enhance the immune response in specific age groups, using a higher dose of HA antigen or the inclusion of an adjuvant. Refer to  in Part 1 of the CIG for more information about inactivated vaccines.
Standard-dose IIVs are available in Canada as quadrivalent formulations (IIV4-SD: Afluria Tetra, Flulaval Tetra, Fluzone Quadrivalent, and Influvac Tetra; IIV4-cc: Flucelvax Quad). These vaccines are un-adjuvanted, contain a standard dose of antigen (15 g HA per strain), and are administered as a 0.5 mL dose by IM injection. Influvac Tetra may be administered by IM or deep subcutaneous injection. Trivalent formulations of standard dose unadjuvanted IIVs are no longer authorized or available for use in Canada.
The adjuvanted IIV currently authorized for use in Canada is a trivalent subunit vaccine (IIV3-Adj) that contains the adjuvant MF59, which is an oil-in-water emulsion composed of squalene as the oil phase that is stabilized with the surfactants polysorbate 80 and sorbitan triolate in citrate buffer. IIV3-Adj contains 7.5 g HA per strain administered as a 0.25 mL dose by IM injection for children 6 to 23 months of age (Fluad Pediatric) or 15 g HA per strain administered as a 0.5 mL dose by IM injection for adults 65 years of age and older (Fluad). Other IIVs do not contain an adjuvant.
There is one high-dose IIV (IIV-HD) currently authorized for use in Canada; a quadrivalent unadjuvanted, split virus IIV that contains 60 g HA per strain and is administered as a 0.7 mL dose by IM injection (Fluzone High-Dose Quadrivalent).

## Recombinant influenza vaccine (RIV)
There is currently only one RIV authorized for use in Canada: Supemtek (RIV4), a quadrivalent unadjuvanted, baculovirus-expressed seasonal influenza vaccine that contains 45 g HA per strain and is administered as a 0.5 mL dose by IM injection for adults 18 years of age and older. RIV contains recombinant HAs produced in an insect cell line using genetic sequences from cell-derived influenza viruses. The production of RIV does not depend on egg supply as it does not require egg-grown candidate vaccine viruses.

## Live attenuated influenza vaccine (LAIV)
LAIV contains standardized quantities of fluorescent focus units (FFU) of live attenuated influenza virus reassortants. The virus strains in LAIV are cold-adapted and temperature sensitive, so they replicate in the nasal mucosa rather than the lower respiratory tract, and they are attenuated, so they do not produce ILI. There have been no reported or documented cases, and no theoretical or scientific basis to suggest transmission of vaccine virus would occur to the individual administering LAIV. As a live replicating whole virus formulation administered intranasally by spray, it elicits mucosal immunity, which may more closely mimic natural infection.
A quadrivalent product (LAIV4; FluMist Quadrivalent) is authorized for use in Canada for children 2 to17 years of age and adults 18 to 59 years of age and is given as a 0.2 mL dose (0.1 mL in each nostril). The trivalent formulation (LAIV3) is no longer available in Canada.

# IV.2 Efficacy, effectiveness, and immunogenicity

## Efficacy and effectiveness
Influenza vaccine has been shown in randomized controlled clinical trials to be efficacious in providing protection against influenza infection and illness. However, the effectiveness of the vaccinethat is, how it performs in settings that are more reflective of usual health care practicecan vary from season to season and by influenza vaccine strain type and subtype. Influenza vaccine effectiveness (VE) depends on how well the vaccine strains match with circulating influenza viruses, the type and subtype of the circulating virus, as well as the health and age of the individual receiving the vaccine. Even when there is a less-than-ideal match or lower VE against one strain, the possibility of lower VE should not preclude vaccination, particularly for people at high risk of influenza-related complications and hospitalization, since vaccinated individuals are still more likely to be protected compared to those who are unvaccinated.

## Immunogenicity
Antibody response after vaccination depends on several factors, including the age of the recipient, prior and subsequent exposure to antigens, and the presence of immune compromising conditions. Protective levels of humoral antibodies, which correlate with protection against influenza infection, are generally achieved by 2 weeks after vaccination; however, there may be some protection afforded before that time.

## Additional information
Because of potential changes in the circulating influenza virus from year to year and waning immunity in vaccine recipients, annual influenza vaccination is recommended. Although some studies suggest vaccine induced protection may be greater in individuals who have no recent vaccine history, overall, the evidence shows no difference in the effectiveness of repeated influenza vaccination compared to vaccination in the current season only. Importantly, optimal protection against influenza is best achieved through annual influenza vaccination, as repeated vaccination including the current season is consistently more effective than no vaccination in the current season. Additional information regarding the effects of repeated influenza vaccination on vaccine effectiveness, efficacy, and immunogenicity can be found in the NACI Recommendation on Repeated Seasonal Influenza Vaccination. NACI will continue to monitor this issue.
NACI acknowledges that evidence related to influenza vaccine performance, particularly with respect to vaccine efficacy and effectiveness, is constantly evolving with advances in research methodology and accumulation of data over many influenza seasons. Therefore, the evidence summarized in  may not include the latest studies. However, NACI continues to closely monitor the emerging evidence on the efficacy and effectiveness, immunogenicity, and safety of influenza vaccines to update and make recommendations when warranted.

# IV.3 Vaccine administration

## Dose, route of administration, and schedule
With the variety of influenza vaccines available for use in Canada, it is important for vaccine providers to note the specific differences in age indication, route of administration, dosage, and schedule for the products that they will be using (see ). Key relevant details and differences between vaccine products are also highlighted in .
For influenza vaccines given by the IM route, the anterolateral thigh muscle is the recommended site in infants 6 to 12 months of age. The anterolateral thigh or the deltoid muscle can be used for toddlers and older children. The deltoid muscle of the arm is the preferred injection site in adolescents and adults. For more information on vaccine administration, please refer to  in Part 1 of the CIG.
The first time that children 6 months to less than 9 years of age receive seasonal influenza vaccination, a two-dose schedule is required to achieve protection. Several studies have looked at whether these two initial doses need to be given in the same season. Englund et al. reported similar immunogenicity in children 6 to 23 months of age whether 2 doses were given in the same or separate seasons when there was no change, or only minor vaccine strain change, in vaccine formulation between seasons. However, seroprotection rates to the B component were considerably reduced in the group that received only one dose in the subsequent season when there was a major B lineage change, suggesting that the major change in B virus lineage reduced the priming benefit of previous vaccination. Issues related to effective prime-boost when there is a major change in influenza B lineage across sequential seasons require further evaluation. Because children 6 to 23 months of age are less likely to have had prior priming exposure to an influenza virus, special effort is warranted to ensure that a two-dose schedule is followed for previously unvaccinated children in this age group.
Afluria Tetra (5 years and older), Flulaval Tetra (6 months and older), Fluzone Quadrivalent (6 months and older), Influvac Tetra (3 years and older).
Flucelvax Quad (6 months and older)
Fluad Pediatric(6 to 23 months) or Fluad(65 years and older)
Fluzone High-Dose Quadrivalent (65 years and older)
SupemtekTM (18 years and older)
FluMist Quadrivalent (2 to 59 years)
Evidence suggests moderate improvement in antibody response in infants, without an increase in reactogenicity, with the use of full vaccine doses (0.5 mL) for unadjuvanted inactivated influenza vaccines. This moderate improvement in antibody response without an increase in reactogenicity is the basis for the full dose recommendation for unadjuvanted inactivated vaccine for all ages. For more information, refer to .
Children 6 months to less than 9 years of age receiving seasonal influenza vaccine for the first time in their life should be given 2 doses of influenza vaccine, with a minimum interval of 4 weeks between doses. Children 6 months to less than 9 years of age who have been properly vaccinated with one or more doses of seasonal influenza vaccine in the past should receive 1 dose of influenza vaccine per season thereafter.

## Booster doses and revaccination
Booster doses are not required within the same influenza season. However, children 6 months to less than 9 years of age who have not previously received the seasonal influenza vaccine require 2 doses of influenza vaccine, with a minimum of 4 weeks between doses. Only one dose of influenza vaccine per season is recommended for everyone else. Two doses of seasonal influenza vaccine in older adults do not appear to improve the immune response to the vaccine compared to one dose.

## Serological testing
Serologic testing is not necessary or recommended before or after receiving seasonal influenza vaccine.

# IV.4 Storage requirements
Influenza vaccine should be stored at +2C to +8C and should not be frozen. Refer to the individual product monographs for further details. Refer to  in Part 1 of the CIG for additional information.

# IV.5 Concurrent administration with other vaccines
All seasonal influenza vaccines, including LAIV, may be given at the same time as, or at any time before or after administration of other vaccines (either live or inactivated), including COVID-19 vaccines for those aged 6 months of age and older as.
NACI will continue to monitor the evidence base, including ongoing and anticipated trials investigating influenza vaccines administered at the same time as, or any time before or after, COVID-19 vaccines and update its recommendations as needed.
No studies were found on potential immune interference between LAIV and other live attenuated vaccines (oral or parenteral) administered within 4 weeks.
Studies on concurrent administration of LAIV3 with measles, mumps, rubella (MMR); measles, mumps, rubella, varicella (MMRV); or live oral polio vaccines did not find evidence of clinically significant immune interference. One study reported a statistically significant but not clinically meaningful decrease in seroresponse rates to rubella antigen when administered concomitantly with LAIV.
In theory, the administration of two live vaccines sequentially within less than 4 weeks could reduce the efficacy of the second vaccine. Possible immune mechanisms include: the inhibitory and immunomodulatory effects of systemic and locally produced cytokines on B- and T-cell response and viral replication; immunosuppression induced by certain viruses (such as measles); and direct viral interference as a result of competition for a common niche. Mucosal vaccines may have less impact on a parenteral vaccine and vice versa. The immune response with a mucosal vaccine may be compartmentalized to the mucosa while that to a parenteral vaccine is systemic. It is likely that there is some interaction between the systemic and mucosal compartments; however, the extent to which this interaction occurs is not known.
Given the lack of data for immune interference, and based on expert opinion, NACI recommends that LAIV can be given together with or at any time before or after the administration of any other live attenuated or inactivated vaccine. However, some vaccine providers may continue to choose to give LAIV and other live vaccines separated by at least 4 weeks, based on the theoretical possibility of immune interference, although NACI does not believe that this precaution is necessary for LAIV. The use of a parenteral inactivated or recombinant influenza vaccine would avoid this theoretical concern. Note that the timing rules related to two parenteral live vaccines (e.g., MMR and varicella vaccines) still apply. For more information regarding vaccination administration timing rules, please refer to  in Part 1 of the CIG.
The target groups for influenza and pneumococcal polysaccharide vaccines overlap considerably. A recent study showed that compared to administration alone, concurrent administration of IIV4 with PCV15 in adults demonstrated non-inferiority of pneumococcal- and influenza-specific antibody responses. The immune response to many PCV components was decreased, but not influenza virus components. The clinical significance of this interaction is not known precisely. Vaccine providers should take the opportunity to vaccinate eligible people against pneumococcal disease when influenza vaccine is given.
When more than one injection is given at a single clinic visit, it is preferable to administer them in different limbs. If it is not possible to do so, injections given in one limb should be separated by a distance of at least 2.5 cm (1 inch). A separate needle and syringe should always be used for each injection.

## Concurrent administration with other adjuvanted vaccines
Data are limited regarding concurrent administration of newer adjuvanted influenza vaccines with other adjuvanted or non-adjuvanted vaccines.
RZV is an example of a recombinant adjuvanted subunit herpes zoster vaccine (Shingrix, GlaxoSmithKline) that is authorized for use in Canada in adults 50 years of age and older, and adults 18 years of age or older who are or will be at increased risk of HZ due to immunodeficiency or immunosuppression caused by known disease or therapy; therefore, the target age group for herpes zoster vaccine and influenza vaccine overlap. RZV has been shown to be safe and effective when given concurrently with unadjuvanted, standard dose influenza vaccines. However, no studies have been conducted that have assessed the concurrent administration of RZV with adjuvanted or high dose influenza vaccine. It should be noted that RZV and IIV-adj currently authorized for use in Canada contain the adjuvants AS01B and MF59 respectively. How these adjuvants may interact when RZV and IIV-adj are administered concurrently is not known.
NACI will continue to review the evidence and update guidance accordingly.

# IV.6 Vaccine safety and adverse events
Post-marketing surveillance of influenza vaccines in Canada has shown that seasonal influenza vaccines have a safe and stable profile. In addition to routine surveillance, every year during the seasonal influenza vaccination campaigns, PHAC and the Federal/Provincial/Territorial Vaccine Vigilance Working Group (VVWG) of the Canadian Immunization Committee conduct weekly expedited surveillance of adverse events following immunization (AEFI) for current influenza vaccines to identify vaccine safety signals in a timely manner. Refer to the  (CAEFISS) web page for more information on post-marketing surveillance and AEFIs in Canada. In addition, the Canadian National Vaccine Safety (CANVAS) Network, a national network of sites across Canada for active vaccine safety surveillance, collects and analyzes information on AEFIs after influenza vaccination to provide influenza vaccine safety information to public health authorities during the core weeks of the annual influenza vaccination campaign.
All influenza vaccines currently authorized for use in Canada are considered safe for use in people with latex allergies. The multi-dose vial formulations of inactivated influenza vaccine that are authorized for use in Canada contain minute quantities of thimerosal, which is used as a preservative to keep the product sterile. Large cohort studies of administrative health databases have found no association between childhood vaccination with thimerosal-containing vaccines and neurodevelopmental outcomes, including autistic-spectrum disorders. All single dose formulations of IIV, RIV and LAIV are thimerosal-free. Refer to  in Part 2 of the CIG for additional information.

## Common adverse events
With IM administered influenza vaccines, injection site reactions are common but are generally classified as mild and transient. IIV3-Adj tends to produce more extensive injection site reactions than un-unadjuvantedIIV3, but these reactions are also generally mild and resolve spontaneously within a few days. IIV-HD tends to induce higher rates of systemic reactions compared to IIV-SD, but most of these reactions are mild and short-lived. Recombinant vaccines appear to have a similar safety profile to IIVs. The most common AEs experienced by recipients of LAIV are nasal congestion and runny nose.

## Less common and serious or severe adverse events
Serious adverse events (SAEs) are rare following influenza vaccination, and in most cases, data are insufficient to determine a causal association. Allergic responses to influenza vaccine are a rare consequence of hypersensitivity to some components of the vaccine or its container.

## Other reported adverse events and conditions

### Egg-allergic individuals
After careful review of clinical and post-licensure safety data, NACI has concluded that egg-allergic individuals may be vaccinated against influenza using any influenza vaccine, including egg-based vaccines and LAIV, without prior influenza vaccine skin test and with the full dose, irrespective of a past severe reaction to egg and without any particular consideration, including vaccination setting. The amount of trace ovalbumin allowed in influenza vaccines that are authorized for use in Canada is associated with a low risk of AE, and in addition, two of the authorized products do not contain any ovalbumin. The observation period post-vaccination is as recommended in  in Part 2 of the CIG. As with all vaccine administration, vaccine providers should be prepared with the necessary equipment, knowledge, and skills to respond to allergic reactions, including anaphylaxis, at all times.

### Guillain-Barre syndrome
In a review of studies conducted between 1976 and 2005, the United States Institute of Medicine concluded that the 1976 "swine flu" vaccine was associated with an elevated risk of GBS. However, evidence was inadequate to accept or to reject a causal relation between GBS in adults and seasonal influenza vaccination. The attributable risk of GBS in the period following seasonal and monovalent 2009 pandemic influenza vaccination is about one excess case per million vaccinations. In a self-controlled study that explored the risk of GBS after seasonal influenza vaccination and after influenza health care encounters (a proxy for influenza illness), the attributable risks were 1.03 GBS admissions per million vaccinations compared with 17.2 GBS admissions per million influenza-coded health care encounters.
These findings suggest that both influenza vaccination and influenza illness are associated with small attributable risks of GBS, but the risk of GBS associated with influenza illness is notably higher than with influenza vaccination. The self-controlled study also found that the risk of GBS after vaccination was highest during weeks 2 to 4, whereas for influenza illness, the risk was greatest within the first week after a health care encounter and decreased thereafter but remained significantly elevated for up to 4 weeks.
Although the evidence considering influenza vaccination and GBS is inadequate to accept or reject a causal relation between GBS in adults and seasonal influenza vaccination, avoiding subsequent influenza vaccination of individuals known to have had GBS without other known etiology within 6 weeks of a previous influenza vaccination appears prudent at this time. However, the potential risk of GBS recurrence associated with influenza vaccination must be balanced against the risk of GBS associated with influenza infection itself and the benefits of influenza vaccination  .

### Oculorespiratory syndrome
Oculorespiratory syndrome (ORS), the presence of bilateral red eyes and one or more associated respiratory symptoms (cough, wheeze, chest tightness, difficulty breathing, difficulty swallowing, hoarseness, or sore throat) that starts within 24 hours of vaccination, with or without facial oedema, was identified during the 20002001 influenza season. Since then, there have been far fewer cases per year reported to CAEFISS. ORS is not an allergic response. People who have an occurrence or recurrence of ORS upon vaccination do not necessarily experience further episodes with future vaccinations.
Individuals who have experienced ORS without lower respiratory tract symptoms may be safely revaccinated with influenza vaccine. Individuals who experienced ORS with lower respiratory tract symptoms should have an expert review. Health care providers who are unsure whether an individual previously experienced ORS versus an immunoglobulin E (IgE) mediated hypersensitivity immune response should seek advice. Data on clinically significant AEs do not support the preference of one vaccine product over another when revaccinating those who have previously experienced ORS.

### Allergic reactions to previous vaccine doses
Expert review of the benefits and risks of vaccination should be sought for those who have previously experienced severe lower respiratory symptoms (wheeze, chest tightness, difficulty breathing) within 24 hours of influenza vaccination, an apparent significant allergic reaction to the vaccine, or any other symptoms that could indicate a significant allergic reaction (e.g., throat constriction, difficulty swallowing) that raise concern regarding the safety of revaccination. This advice may be obtained from experts in infectious disease, allergy, and immunology, or public health that can be found in various health settings, including the .
In view of the considerable morbidity and mortality associated with influenza and rarity of true vaccine allergy, a diagnosis of allergy to an influenza vaccine should not be made without confirmation, which may involve consultation with an allergy or immunology expert.

### Drug interactions
Although influenza vaccine can inhibit the clearance of warfarin and theophylline, clinical studies have not shown any adverse effects attributable to these drugs in people receiving influenza vaccine. Statins have effects on the immune system in addition to their therapeutic cholesterol-lowering actions. Two published studies have found that adults who are regular statin users (at least 65 years of age in one study and 45 years and older in the other) had a decreased response to influenza vaccination as measured by reduced geometric mean titres (GMT) or reduced VE against medically attended acute respiratory illness. Statins are widely used in the same adult populations who are also at-risk for influenza-related complications and hospitalizations. Therefore, if these preliminary findings are confirmed in future studies, concurrent statin use in adult populations could have implications for influenza VE and how this use is assessed in the measurement of VE. NACI will continue to monitor the literature related to this issue.

### Guidance on reporting adverse events following immunization
To ensure the ongoing safety of influenza vaccines in Canada, reporting of AEFIs by vaccine providers and other clinicians is critical, and in most jurisdictions, reporting is mandatory under the law.
An AEFI is any untoward medical occurrence that follows vaccination whether or not there is a causal relationship with the usage of a vaccine. The AEFI may be any unfavourable or unintended sign, abnormal laboratory finding, symptom, or disease. Any AEFI temporally related to vaccination and for which there is no other clear cause at the time of reporting should be reported. Of particular importance are those AEFIs which are serious or unexpected. A serious AEFI is an adverse event that is life threatening or results in death, requires hospitalization or prolongs an existing hospitalization, results in residual disability or causes congenital malformation. An unexpected AEFI is an event that is not listed in the approved product monograph but may be due to the vaccination, or one whose nature, severity, specificity, or outcome is not consistent with the term or description used in the product monograph. Vaccine providers are asked to  and to check for specific AEFI reporting requirements in their province or territory. If there is any doubt as to whether or not an event should be reported, a conservative approach should be taken, and the event should be reported.
For influenza vaccines, the following AEFIs are of particular interest:
- ORS; and
- GBS within 6 weeks following vaccination
V. Recommendations
NACI makes the following recommendations for individual-level and public health program-level decision making. Individual-level recommendations are intended for people wishing to protect themselves from influenza or for vaccine providers wishing to advise individual patients about preventing influenza. Program-level recommendations are intended for provinces and territories responsible for making decisions on publicly funded immunization programs. Individual-level and program-level recommendations may differ, as the important factors to consider when recommending a vaccine for a population (e.g., population demographics, economic considerations) may be different than for an individual.
Recommendation for individual-level decision making
NACI recommends that influenza vaccine should be offered annually to anyone 6 months of age and older who does not have a contraindication to the vaccine, with focus on the groups for whom influenza vaccination is particularly recommended (see ).
Recommendations for public health program-level decision making
The national goal of the annual influenza immunization programs in Canada is to prevent serious illness caused by influenza and its complications, including death. Programmatic decisions to provide influenza vaccination to target populations as part of publicly funded provincial and territorial programs depend on many factors, such as cost-effectiveness evaluation and other programmatic and operational factors, such as implementation strategies.
- NACI recommends that influenza vaccine should be offered as a priority to the groups for whom influenza vaccination is particularly recommended (see  in the section below).

## List 1: Groups for whom influenza vaccination is particularly recommended
People at high risk of influenza-related complications or hospitalization
- All children 6 to 59 months of age
- Adults and children with the following chronic health conditions:
	+ Cardiac or pulmonary disorders (includes bronchopulmonary dysplasia, cystic fibrosis, and asthma);
	+ Diabetes mellitus and other metabolic diseases;
	+ Cancer, immune compromising conditions (due to underlying disease, therapy, or both, such as solid organ transplant or hematopoietic stem cell transplant recipients);
	+ Renal disease;
	+ Anemia or hemoglobinopathy;
	+ Neurologic or neurodevelopmental conditions (includes neuromuscular, neurovascular, neurodegenerative, neurodevelopmental conditions, and seizure disorders 
	+ Morbid obesity (defined as BMI of 40 kg/m2 and over); and
	+ Children 6 months to 18 years of age undergoing treatment for long periods with acetylsalicylic acid, because of the potential increase of Reye's syndrome associated with influenza
- All individuals who are pregnant;
- People of any age who are residents of nursing homes and other chronic care facilities;
- Adults 65 years of age and older; and
- Indigenous peoples.
People capable of transmitting influenza to those at high risk
- Health care and other care providers in facilities and community settings who, through their activities, are capable of transmitting influenza to those at high risk
- Household contacts, both adults and children, of individuals at high risk, whether or not the individual at high risk has been vaccinated:
	+ household contacts of individuals at high risk
	+ household contacts of infants less than 6 months of age, as these infants are at high risk but cannot receive influenza vaccine
	+ members of a household expecting a newborn during the influenza season;
- Those providing regular child care to children 0 to 59 months of age, whether in or out of the home; and
- Those who provide services within closed or relatively closed settings to people at high risk (e.g., crew on a cruise ship).
Others
- People who provide essential community services; and
- People who are in direct contact with poultry infected with avian influenza during culling operations
List 1 - Footnote a
List 1 - Footnote b

# V.1 Choice of seasonal influenza vaccine
With the recent availability of a number of new influenza vaccines, some of which are designed to enhance immunogenicity in specific age groups, the choice of product is now more complex.
- IIV4-SD
- IIV4-cc
	+ Currently, there is insufficient evidence for recommending vaccination with Influvac Tetra (IIV4-SD) in children younger than 3 years of age.
- If a quadrivalent vaccine is not available, a trivalent vaccine licensed for this age group should be used.
- IIV4-cc
- LAIV4
	+ Currently, there is insufficient evidence for recommending vaccination with Influvac Tetra (IIV4-SD) in children younger than 3 years of age.
- LAIV4 may be given to children with:
	+ stable, non-severe asthma;
	+ cystic fibrosis who are not being treated with immunosuppressive drugs (e.g., prolonged systemic corticosteroids); and
	+ stable HIV infection, i.e., if the child is currently being treated with ART (i.e., HAART) for at least 4 months and has adequate immune function.
- LAIV should not be used in children or adolescents for whom it is contraindicated or for whom there are warnings and precautions such as those with:
	+ severe asthma (defined as currently on oral or high-dose inhaled glucocorticosteroids or active wheezing);
	+ medically attended wheezing in the 7 days prior to vaccination;
	+ current receipt of aspirin or aspirin-containing therapy;
	+ immune compromising conditions, with the exception of stable HIV infection, i.e., if the child is currently being treated with HAART for at least 4 months and has adequate immune function;
	+ pregnancy
		- in pregnancy, IIV4-SD or IIV4-cc should be used instead.
- IIV4-cc
- RIV4
- LAIV4
	+ There is some evidence that IIV may provide better efficacy than LAIV in healthy adults; and
- LAIV is not recommended for:
	+ Pregnant individuals
		- in pregnancy, IIV4-SD, IIV4-cc or RIV4 should be used instead.
	+ adults with any of the chronic health conditions identified in , including immune compromising conditions; and
	+ health care workers
- IIV4-cc
- RIV4
- IIV4-SD
- IIV4-HD
- IIV4-cc
- RIV4
	+ Other than a recommendation for using IIV-HD over IIV-SD formulations, NACI has not made comparative individual-level recommendations on the use of the other available vaccines in this age group. In the absence of a specific product, any of the available age-appropriate influenza vaccines should be used.
	+ There is insufficient evidence on the incremental value of different influenza vaccines (i.e., cost-effectiveness assessments have not been performed by NACI) to make comparative public health program-level recommendations on the use of the available vaccines.
IIV3-SD formulations will not be authorized or available for use in Canada during the 2023-2024 influenza season.
IIV3-HD formulations will not be authorized or available for use in Canada during the 2023-2024 influenza season.

# V.2 Children

## Burden of disease in children
Children experience a higher burden of disease due to influenza B infection compared to other age groups. Although children less than 24 months of age comprise approximately 2% of the Canadian population, children 0 to 23 months of age averaged 10.8% of reported influenza B cases (range: 8.3 to 13.7%), using case-based laboratory data from 20012012 (excluding 2009). With respect to severe outcomes (e.g., hospitalization, intensive care unit admission, and death), influenza B was confirmed in 15.5 to 58.3% (median: 38.4%) of pediatric influenza-associated hospitalizations (children 16 years of age and younger) reported by the Canadian Immunization Monitoring Program Active (IMPACT) surveillance network between 20042005 and 20122013 (excluding the 20092010 pandemic season). From 2010-2011 to 2018-2019, inclusively, 29% of IMPACT influenza admissions were for influenza B.
The IMPACT study also found that the proportion of deaths attributable to influenza (any strain) was significantly greater for children admitted to hospital with influenza B (1.1%) than for those admitted with influenza A (0.4%). The proportion of hospitalizations due to influenza B relative to all influenza hospitalizations has been generally similar to the proportion of influenza B detections relative to all influenza infections in the general population during the same time period. Additional information can be found in the 
In the NACI , a review of B lineage antigens included in the Canadian influenza vaccines and the circulating strains each season indicates a match in five of the 12 seasons from 20012002 through to 20122013, a moderate match (about 50% from each lineage) in 1 season, and a mismatch in remaining 6 influenza seasons (i.e., 70% or more of the characterized B strains were of the opposite lineage to the antigen in that season's vaccine).

## Children 6 to 23 months of age
Three types of influenza vaccine are authorized and available for use in children 6 to 23 months of age: IIV3-Adj, IIV4-SD, and IIV4-cc.
Given the burden of influenza B disease in children and the potential for lineage mismatch between the predominant circulating strain of influenza B and the strain in a trivalent vaccine, NACI recommends that a quadrivalent influenza vaccine should be used. If a quadrivalent vaccine is not available, an available age-appropriate trivalent vaccine (IIV3-Adj) should be used.
The current evidence is insufficient for recommending vaccination with Influvac Tetra (IIV4-SD) in children younger than 3 years of age.

## Children 2 to 17 years of age
Three types of influenza vaccine are authorized and available for use in children 2 to 17 years of age: IIV4-SD, IIV4-cc, and LAIV4.
The current evidence does not support a recommendation for the preferential use of LAIV in children and adolescents 2 to 17 years of age. Refer to the NACI  for information supporting this recommendation.
The current evidence is insufficient for recommending vaccination with Influvac Tetra (IIV4-SD) in children younger than 3 years of age.

### Children 2 to 17 years of age with chronic health conditions
NACI recommends that any age-appropriate influenza vaccine (IIV or LAIV) may be considered for children 2 to 17 years of age with chronic health conditions; however, LAIV should not be used for children with severe asthma (as defined as currently on oral or high-dose inhaled glucocorticosteroids or with active wheezing), those with medically attended wheezing in the 7 days prior to vaccination, those currently receiving aspirin or aspirin-containing therapy, and those with immune compromising conditions, excluding those with stable HIV infection on HAART and with adequate immune function. LAIV is also contraindicated in adolescents who are pregnant. Children and adolescents for whom LAIV is contraindicated should receive IIV. If IIV is used, NACI recommends that a quadrivalent vaccine should be used. If a quadrivalent vaccine is not available, an age-appropriate trivalent vaccine should be used.
NACI recommends that LAIV may be given to children with stable, non-severe asthma, children with cystic fibrosis who are not treated with immunosuppressive drugs, such as prolonged systemic corticosteroids, and children with stable HIV infection on HAART and with adequate immune function.

### Summary of vaccine characteristics for decision making
IIV4-SD, IIV4-cc, and LAIV4 are authorized for use in Canada for children 2 to 17 years of age. The comparison of the vaccine characteristics of IIV and LAIV, in  below, may be considered in deciding on the preferred vaccine option(s) for use by an individual or a public health program. Note that although data comparing LAIV to IIV4-cc are not available, IIV-cc is comparable to egg-based IIV.
NACI has not assessed the comparative cost-effectiveness of authorized influenza vaccine types for children 2 to 17 years of age.
The trivalent formulation of LAIV (LAIV3) received a Notice of Compliance from Health Canada in June 2010 and was first used in publicly funded immunization programs in Canada for the 20122013 influenza season. The quadrivalent formulation (LAIV4) was approved for use in Canada for the 20142015 season and has been in use since that time. LAIV3 is no longer available in Canada.
The trivalent IIV3-SD formulations are not expected to be authorized or available in Canada for the 2023-2024 influenza season. Data comparing LAIV to IIV4-cc are not available, however IIV-cc is comparable to egg-based IIV.

# V.3 Adults

## Burden of disease in adults
A study focusing on estimates of deaths associated with influenza in the United States has established that the average annual rate of influenza-associated deaths for adults aged 65 years of age and older was 17.0 deaths per 100,000 (range: 2.4 to 36.7). The study also states that of deaths coded as being influenza- or pneumonia-related, persons 65 years of age and older accounted for 87.9% of the overall estimated annual average number of deaths. When influenza-related deaths among adults 65 years of age and older were estimated using codes for underlying respiratory and circulatory causes of death, these estimates increased to 66.1 deaths per 100,000 (range: 8.0 to 121.1) and 89.4%, respectively. This study described a wide variation in the estimated number of deaths from season to season, which was closely related to the influenza virus types and subtypes in circulation. Estimates presented in the study of yearly influenza-associated deaths with underlying pneumonia and influenza causes (1976 to 2007) reveal a large difference between influenza type A and B with a calculated median of greater than 6,000 deaths associated with influenza type A and half of that number for influenza type B (approximately 3,360) for persons 65 years of age and older. During the 22 seasons in which influenza A(H3N2) was the prominent strain, the average influenza-associated mortality rates were 2.7 times higher than for the nine seasons that it was not (all age groups combined), and on average, there were about 37% more annual influenza-associated deaths, regardless of the primary medical cause of death. A higher risk of hospitalization and death was also reported by Cromer et al. in adults 65 years of age and older, compared to younger adults in their assessment of the burden of influenza in England by age and clinical risk group.
Canadian surveillance data show that hospitalization rates among adults 65 years of age and older were higher during the A(H3N2)-predominant 20142015 season compared to the previous five influenza seasons and also compared to the 20122013 season when A(H3N2) also predominated; 20142015 was a season in which there was a vaccine mismatch with the circulating A(H3N2) strain. Similar to the hospitalization rates, death rates among older adults were highest in the 20142015 season compared to the previous five seasons and compared to the previous A(H3N2) season in 20122013. Mortality rates among other age groups were similar to or lower than the previous five influenza seasons. Laboratory detections over this same time period showed that influenza seasons in which influenza subtype A(H3N2) predominated, disproportionally affected adults 65 years of age and older, while seasons with greater A(H1N1) detections resulted in a higher proportion of positive cases in younger age groups.

## Adults 18 to 59 years of age
Four types of influenza vaccine are authorized and available for use in adults 18 to 59 years of age: IIV4-SD, IIV4-cc, RIV4, and LAIV4.
NACI recommends that any of the available influenza vaccines should be used in adults without contraindications to the vaccine. NACI previously found insufficient evidence to recommend the use of LAIV in adults with chronic health conditions due to the potentially better immune response following IIV compared to LAIV in healthy adults in some studies. As such, IIV or RIV should be used for adults with chronic health conditions identified in , HCWs or individuals who are pregnant (noting that limited published clinical data pertaining to safety of vaccination with RIV4 during pregnancy is currently available to inform vaccine-associated risks for this population). For further information, refer to .

## Adults 60 to 64 years of age
Three types of influenza vaccine are authorized and available for use in adults 60 to 64 years of age: IIV4-SD, IIV4-cc, and RIV4.
NACI recommends that any of the available age-appropriate influenza vaccines should be used.

## Adults 65 years of age and older
Five types of influenza vaccine are authorized and available for use in adults 65 years of age and older: IIV3-Adj, IIV4-SD, IIV4-cc, IIV4-HD, and RIV4.

### Recommendation for individual-level decision making
When available, IIV-HD should be used over IIV-SD, given the burden of influenza A(H3N2) disease and the good evidence of better protection of IIV3-HD compared to IIV3-SD in adults 65 years of age and older. Based on a review of pre-authorization trials, IIV4-HD is non-inferior to IIV3-HD and is therefore expected to provide the same enhanced protection against A(H3N2) compared to SD IIV, including IIV4-SD. Although IIV-HD is expected to provide better protection against influenza A(H3N2) for adults 65 years of age or older, the benefit of providing this vaccine to all adults 65 and over as opposed to any other influenza vaccine is not clear (refer to the next section). NACI is currently conducting an updated review of influenza vaccines in this population.
Any of the available influenza vaccines would be preferable to remaining unvaccinated or requesting individuals to return for vaccine. Therefore, in the absence of a specific product, NACI recommends that any of the available influenza vaccines authorized for this age group should be used.

### Recommendation for public health program-level decision making
IIV3-HD is expected to provide better protection compared to IIV3-SD. Similarly, IIV4-HD is expected to provide better protection compared to IIV4-SD. The previous assessment completed by NACI demonstrated insufficient evidence to make a comparative recommendation on the use of IIV3-HD over IIV3-SD at the programmatic level and a complete assessment that includes economic considerations has not yet been conducted for IIV4-HD. Therefore, NACI currently recommends that any of the available influenza vaccines should be used for public health programs. NACI is in the process of completing an updated assessment on influenza vaccines for adults 65 years of age and older.

### Summary of vaccine characteristics for decision making
There are four types of inactivated influenza vaccines (IIV3-Adj, IIV4-SD, IIV4-cc, and IIV4-HD) and one type of recombinant influenza vaccine (RIV4) authorized for use in Canada for adults 65 years of age and older. The comparison of vaccine characteristics across vaccine types, in  below, may be considered when deciding on the preferred vaccine option(s) for use by an individual or a public health program. Due to the limited available data directly comparing the performance of IIV3-Adj, IIV-HD, IIV4-SD, IIV4-cc, or RIV4, considerations for these vaccines in  are compared to IIV3-SD for which comparative data on efficacy, effectiveness, and/or immunogenicity with each of IIV3-Adj and IIV4-SD are available. Data directly comparing IIV4-cc and IIV4-HD to IIV3-SD are not available. Comparative data on efficacy, effectiveness, and/or immunogenicity of IIV3-cc and IIV3-SD are available.
NACI has not assessed the comparative cost-effectiveness of available influenza vaccine types for adults 65 years of age and older.
Data directly comparing IIV4-HD to IIV3-SD are not available; however, IIV4-HD has been shown to be non-inferior to IIV3-HD and has a comparable rate of systemic and local reactions. Therefore, information presented here is expected to apply to IIV4-HD as well.
Data directly comparing IIV4-cc to IIV3-SD are not available; however, IIV3-cc (licensure never sought in Canada) has been shown to be non-inferior to IIV3-SD. Therefore, information presented here is expected to apply to IIV4-cc as well.
Data directly comparing RIV4 to IIV3-SD are not available; however, RIV4 has been shown to provide better protection than IIV4-SD based on one study conducted during a single influenza season (2014-2015).
Data directly comparing RIV4 to IIV3-SD are not available; however, RIV4 has been shown to be non-inferior to IIV4-SD, IIV4-cc, IIV3-HD and IIV3-Adj against all tested influenza strains  and has a comparable rate of AEs based on 3 influenza seasons (2014-2015, 2017-2018, 2018-2019). Therefore, information presented here is expected to apply to IIV3-SD as well.

## Adults with chronic health conditions
NACI recommends that any age-appropriate IIV or RIV, but not LAIV, should be offered to adults with chronic health conditions identified in , including those with immune compromising conditions.

## Pregnant individuals
NACI recommends that any age-appropriate IIV or RIV, but not LAIV, should be offered to pregnant individuals (noting that limited published clinical data pertaining to safety of vaccination with RIV4 during pregnancy is currently available to inform vaccine-associated risks).
Due to a lack of safety data at this time, LAIV should not be administered to pregnant individuals due to the theoretical risk to the fetus from administering a live virus vaccine. LAIV can be administered to breastfeeding individuals.

## Health care workers
NACI recommends that any age-appropriate IIV or RIV, but not LAIV, should be offered to HCWs.
Comparative studies in healthy adults have found IIV to be similarly or more efficacious or effective compared with LAIV. In addition, as a precautionary measure, LAIV recipients should avoid close association with people with severe immune compromising conditions (e.g., bone marrow transplant recipients requiring isolation) for at least 2 weeks following vaccination, because of the theoretical risk for transmitting a vaccine virus and causing infection.

## Travellers
Influenza occurs year-round in the tropics. In temperate northern and southern countries, influenza activity generally peaks during the winter season (November to March in the Northern Hemisphere and April to October in the Southern Hemisphere).
- NACI recommends that influenza vaccine should be offered annually to anyone 6 months of age and older, including travellers, who does not have a contraindication to the vaccine, with focus on the groups for whom influenza vaccination is particularly recommended (see ).
Vaccines prepared specifically for use in the Southern Hemisphere are not available in Canada, and the extent to which recommended vaccine components for the Southern Hemisphere may overlap with those in available Canadian formulations will vary. A decision for or against revaccination (i.e., boosting) of travellers to the Southern Hemisphere between April and October, if they had already been vaccinated in the preceding fall or winter with the Northern Hemisphere's vaccine, depends on individual risk assessment, the similarity between the Northern and Southern Hemisphere vaccines, the similarity between the Northern Hemisphere vaccine strains and currently circulating strains in the Southern Hemisphere, and the availability of a reliable and safe vaccine at the traveller's destination. Refer to  in Part 3 of the CIG for additional general information.

# V.4 Particularly recommended vaccine recipients
The groups for whom influenza vaccination is particularly recommended are presented in . Additional information regarding these particularly recommended recipients is provided below.

## All children 6 to 59 months of age
On the basis of existing data, NACI recommends the inclusion of all children 6 to 59 months of age among those for whom influenza vaccine is particularly recommended.

## Adults and children with chronic health conditions
As noted in , a number of chronic health conditions are associated with increased risk of influenza-related complications and can be exacerbated by a flu infection. Influenza vaccination can induce protective antibody levels in a substantial proportion of adults and children with immune-compromising conditions, including transplant recipients, those with proliferative diseases of the hematopoietic and lymphatic systems, and HIV-infected people. Vaccine effectiveness may be lower in people with immune compromising conditions than in healthy adults.

## All individuals who are pregnant
NACI recommends the inclusion of all individuals who are pregnant, at any stage of pregnancy, among those who are particularly recommended to receive IIV or RIV. This is due to the risk of influenza-associated morbidity amongst those who are pregnant   , evidence of adverse neonatal outcomes associated with respiratory hospitalization during pregnancy or influenza during pregnancy , evidence that vaccination of individuals who are pregnant protects their newborns from influenza and influenza-related hospitalization  , and evidence that infants born during influenza season to vaccinated individuals are less likely to be premature, small for gestational age, and of low birth weight than if born to individuals that had not received an influenza vaccine  . The risk of influenza-related hospitalization increases with length of gestation (i.e., it is higher in the third trimester than in the second).
The safety of IIV during pregnancy has been reviewed. Active studies of influenza vaccination during pregnancy have not shown evidence of harm to the pregnant individual or fetus associated with influenza vaccination. Although the cumulative sample size of active studies of influenza vaccination in pregnant individuals is relatively small, particularly in the first trimester, passive surveillance has not raised any safety concerns despite widespread use of IIV during pregnancy over several decades  . Surveillance following the use of both adjuvanted and un-adjuvanted 2009 pandemic influenza A(H1N1) vaccines in more than 100,000 pregnant women in Canada and more than 488,000 pregnant women in Europe has not revealed any safety concerns.
Very limited peer-reviewed, published data pertaining to safety of vaccination with RIV4 during pregnancy is currently available to inform vaccine-associated risks. Refer to the  for more information.

## People of any age who are residents of nursing homes and other chronic care facilities
Residents of nursing homes and other chronic care facilities often have one or more chronic health condition and live in institutional environments that may facilitate the spread of influenza.

## Adults 65 years of age and older
Hospitalization attributable to influenza in this age group is estimated at 125 to 228 per 100,000 healthy people, and influenza-attributed mortality rates increase with increased age.

## Indigenous peoples
Based on a body of evidence indicating a higher rate of influenza-associated hospitalization and death among Indigenous peoples, NACI recommends the inclusion of this population among those for whom the influenza vaccine is particularly recommended.
It has been proposed that the increased risk of severe influenza outcomes in the Indigenous populations is a consequence of many factors, including high prevalence of chronic health conditions (e.g., diabetes, chronic lung disease, end-stage kidney disease, cardiovascular disease, obesity), delayed access to health care, and increased susceptibility to disease because of poor housing and overcrowding. A review of the available evidence and update to the recommendations for Indigenous peoples as a group at high-risk of influenza-related complications is planned, with inclusion and consideration of key stakeholder engagement.

# V.5 People capable of transmitting influenza to those at high risk of influenza-related complications or hospitalization
People who are potentially capable of transmitting influenza to those at high risk should receive annual vaccination, regardless of whether the high-risk individual has been vaccinated. Vaccination of Health Care Workers (HCWs) decreases their own risk of illness, as well as the risk of death and other serious outcomes among the individuals for whom they provide care  . Vaccination of HCWs and residents of nursing homes is associated with decreased risk of ILI outbreaks.
People who are more likely to transmit influenza to those at high risk of influenza-related complications or hospitalization include:
- HCWs and other care providers in facilities and community settings who, through their activities, are capable of transmitting influenza to those at high risk; and
- Contacts, both adults and children, of individuals at high risk, whether or not the individual at high risk has been vaccinated

## Health care workers and other care providers in facilities and community settings

### Vaccination of health care workers and other care providers
For the purposes of this statement, HCWs and other care providers in facilities and community settings refers to HCWs, essential care providers, emergency response workers, those who work in continuing care or long-term care facilities or residences, those who provide home care for people at high risk, and students of related health care services. HCWs include any person, paid or unpaid, who provides services, works, volunteers, or trains in a hospital, clinic, or other health care facility.
Transmission of influenza to patients at high risk of influenza-associated complications results in significant morbidity and mortality. Four cluster randomized controlled trials (RCTs) conducted in geriatric long-term care settings have demonstrated that vaccination of HCWs is associated with substantial decreases in influenza-like illness and all-cause mortality in the residents. In addition, due to their occupation and close contact with people who may be infected with influenza, HCWs are themselves at increased risk of infection.
As previously stated, children 0 to 59 months of age, adults and children with chronic health conditions, pregnant individuals, people of any age who are residents of nursing homes and other chronic care facilities, and adults 65 years of age and older are at greater risk of more severe complications from influenza or worsening of their underlying condition. Given the potential for HCWs and other care providers to transmit influenza to individuals at high risk and knowing that vaccination is the most effective way to prevent influenza, NACI recommends that, in the absence of contraindications, HCWs and other care providers in facilities and community settings should be vaccinated against influenza annually. NACI considers the receipt of influenza vaccination to be an essential component of the standard of care for all HCWs and other care providers for their own protection and that of their patients. This group should consider annual influenza vaccination as part of their responsibilities to provide the highest standard of care.
Although the current influenza vaccine coverage rate for HCWs is higher than for the general public, it remains below the national goal of 80% coverage for HCWs in Canada. Comprehensive vaccination programs should be adopted that address HCWs' acceptance of the vaccine and facilitate the process of vaccinating HCWs to improve uptake of the influenza vaccine beyond the current level. HCW influenza vaccination programs that have successfully increased vaccine coverage of HCWs have included a combination of education, increased awareness, accessible on-site vaccination delivery options for all HCWs, visible support from senior staff and other leaders, and regular review and improvement of vaccination strategies   .

### Outbreak management in health care facilities
As noted in PHAC's *,- all health care organizations should have a written plan for managing an influenza outbreak in their facilities. Inherent in such plans should be policies and programs to optimize HCW's influenza vaccination. As part of outbreak management, the above-mentioned PHAC guidance suggests consideration of chemoprophylaxis for all unvaccinated HCWs, unless contraindications exist. Refer to the  Canada (AMMI Canada) website for guidelines regarding the use of antiviral medications for prophylaxis.

## Contacts of individuals at high risk of influenza complications
Vaccination is recommended for contacts, both adults and children, of individuals at high risk of influenza-related complications or hospitalization (see ), whether or not the individual at high risk has been vaccinated. These contacts include: household contacts and care providers of individuals at high risk, household contacts and care providers of infants less than 6 months of age (as these infants are at high risk of complications from influenza but cannot receive influenza vaccine), members of a household expecting a newborn during the influenza season, household contacts and care providers (whether in or out of the home) of children 0 to 59 months of age, and providers of services within closed or relatively closed settings with people at high risk of influenza-related complications (e.g., crew on a passenger or cruise ship).

# V.6 Others

## People who provide essential community services
Vaccination for these individuals should be encouraged to minimize the disruption of services and routine activities during annual influenza epidemics. People who provide essential community services, including healthy working adults, should consider annual influenza vaccination, as this intervention has been shown to decrease work absenteeism due to respiratory and related illnesses   .

## People in direct contact with poultry infected with avian influenza during culling operations

### Poultry handlers
Although seasonal influenza vaccination will not prevent avian influenza infection, some countries and provinces have recommended influenza vaccination on a yearly basis for those working with poultry, based on the rationale that preventing infection with human influenza strains may reduce the theoretical potential for human-avian reassortment of genes, should such workers become co-infected with human and avian influenza viruses.
NACI recommends seasonal influenza vaccination for people who may be in direct contact with poultry infected with avian influenza during culling operations, as these individuals may be at increased risk of avian influenza infection because of exposure during the culling operation  . Refer to the  for further information supporting this recommendation.
Direct contact may be defined as sufficient contact with infected poultry to allow transmission of an avian virus to the exposed person. The relevant individuals include those performing the cull, as well as others who may be directly exposed to the avian virus, such as supervising veterinarians and inspectors. It is recommended that biosecurity measures such as personal protective equipment and antivirals be used. Refer to  for PHAC recommendations on the management of domestic avian influenza outbreaks.

### Swine workers
NACI has concluded that there is insufficient evidence at this time to recommend routine influenza vaccination specifically for swine workers; however, NACI recommends that influenza vaccination should be offered to anyone 6 months of age and older who does not have contraindications to the vaccine.