Summary of the National Advisory Committee on Immunization ( NACI ) Statement on Seasonal Influenza Vaccine for 2016 – 2017

Background: Influenza is a respiratory infection caused primarily by influenza A and B viruses. Vaccination is the most effective way to prevent influenza and its complications. The National Advisory Committee on Immunization (NACI) provides recommendations regarding seasonal influenza vaccines annually to the Public Health Agency of Canada (the Agency). Objective: To summarize the NACI recommendations regarding the use of seasonal influenza vaccines for the 2016-2017 influenza season. Methods: Annual influenza vaccine recommendations are developed by NACI’s Influenza Working Group for consideration and approval by NACI, based on NACI’s evidence-based process for developing recommendations, and include a consideration of the burden of influenza illness and the target populations for vaccination; efficacy and effectiveness, immunogenicity and safety of influenza vaccines; vaccine schedules; and other aspects of influenza immunization. These recommendations are published annually on the Agency’s website in the NACI Advisory Committee Statement: Canadian Immunization Guide Chapter on Influenza and Statement on Seasonal Influenza Vaccine (the Statement). Results: The annual NACI seasonal influenza vaccine recommendations have been updated for the 2016-2017 influenza season to include adults with neurologic or neurodevelopment conditions among the groups for whom influenza vaccination is particularly recommended; to include the new high-dose, trivalent inactivated influenza vaccine for use in adults 65 years of age and older; to recommend that egg-allergic individuals may also be vaccinated against influenza using the low ovalbumin-containing live attenuated influenza vaccine (LAIV) licensed for use in Canada (NACI has previously recommended that egg-allergic individuals may be vaccinated using inactivated influenza vaccines); and to remove the preferential recommendation for the use of LAIV in children 2–17 years of age. Two addenda to the 2016-2017 Statement address these new LAIV recommendations. Conclusion: NACI continues to recommend annual influenza vaccination for all individuals aged six months and older, with particular focus on people at high risk of influenza-related complications or hospitalization, people capable of transmitting influenza to those at high risk and others as indicated. Affiliations 1 Chair, National Advisory Committee on Immunization 2 Kingston, Frontenac and Lennox & Addington Public Health, Kingston, ON 3 Centre for Immunization and Respiratory Infectious Diseases, Public Health Agency of Canada, Ottawa, ON 4 NACI membership provided in Acknowledgements *Correspondence: naci-ccni@ phac-aspc.gc.ca


Introduction
Influenza is ranked among the top 10 leading causes of death in Canada (1).Although the burden of influenza can vary from year to year, it is estimated that, in a given year, there are an average of 12,200 hospitalizations related to influenza (2) and approximately 3,500 deaths attributable to influenza (3).The National Advisory Committee on Immunization (NACI) provides recommendations regarding seasonal influenza vaccines annually to the Public Health Agency of Canada (the Agency).NACI recommendations for the use of seasonal influenza vaccine for the 2016 -2017 influenza season is summarized below.Complete details can be found in the Statement on Seasonal Influenza Vaccine for 2016-2017 (4), which includes the Canadian Immunization Guide Chapter on Influenza (Section II of the Statement) and in the two addenda to the Statement (5,6) published on the Agency's website.

Methods
In order to prepare the 2016-2017 seasonal influenza vaccine recommendations, NACI's Influenza Working Group (IWG) identified and reviewed evidence regarding adults with neurologic or neurodevelopment conditions as a risk group for complications of influenza; the new high-dose, trivalent inactivated influenza vaccine licensed for use in adults 65 years of age and older (Fluzone ® High-Dose [Sanofi Pasteur]); the administration of live attenuated influenza vaccine (LAIV) in egg-allergic individuals; and vaccine effectiveness (VE) of LAIV and inactivated influenza vaccine.Following the review and analysis of this information, the IWG proposed updated recommendations for vaccine use to NACI, based on NACI's evidence-based process for developing recommendations (7).NACI critically appraised the available evidence and approved the specific recommendations brought forward.The evidence review regarding Fluzone ® High-Dose is published separately (8).The rationale and relevant considerations for all the updated recommendations are included in the full Statement for 2016-2017 (4) and the two addenda to the 2016-2017 Statement on LAIV use (5,6).

Results
New for the 2016-2017 influenza season:

Adults with neurologic or neurodevelopment conditions
As of 2015-2016, children and adolescents with neurologic or neurodevelopment conditions, including seizure disorders, febrile seizures and isolated developmental delay, have been included in the high-risk group for whom influenza vaccine is particularly recommended.Based on preliminary review of the literature and expert opinion, and consistent with other countries' recommendations, NACI now includes adults with neurologic or neurodevelopment conditions in the high-risk group for whom influenza vaccine is particularly recommended.From the preliminary review, it was noted that the odds ratios for influenza complications in patients with neurologic conditions in comparison to those without in the reviewed studies ranged from 1.57 (pneumonia: 95% confidence interval [CI], 1.05 to 2.36) to 19.11 (intensive care unit admission: 95% CI, 3.92 to 93.22) and 22.2 (hospitalization: 95% CI, 2.6 to 186.0) (9)(10)(11).The conditions identified as risk factors in the studies reviewed include neuromuscular, neurovascular, neurodegenerative, neurodevelopmental conditions and seizure disorders.
The preliminary literature review findings, rationale, and updated NACI recommendation for the inclusion of adults with neurologic or neurodevelopment conditions are published in the 2016-2017 Statement (4).

New high-dose, trivalent inactivated influenza vaccine (Fluzone ® High-Dose [Sanofi Pasteur])
Fluzone ® High-Dose influenza vaccine has been approved for use in Canada in adults 65 years of age and older.Fluzone ® High-Dose is a trivalent inactivated influenza vaccine (TIV) containing 60 µg of haemagglutinin (HA) per strain (compared to 15 µg HA per strain in a standard dose), administered as a 0.5 mL dose by intramuscular injection.Based on the available evidence, NACI concludes that there is evidence that high-dose TIV should provide superior protection compared with standard-dose TIV for adults 65 years of age and older.This superior relative protection compared to standard-dose TIV appears to increase with increasing age over 65 years.Considering the burden of disease associated with influenza A(H3N2) and the evidence of superior efficacy of high-dose TIV compared to standard-dose TIV, it appears that high-dose TIV would provide the greatest benefit to people 65 years of age and older.
A complete literature review of the Fluzone ® High-Dose influenza vaccine for adults 65 years of age and older is published separately (8) and the full NACI rationale and recommendations on its use are published in the 2016-2017 Statement (4).

Administration of LAIV to egg-allergic individuals
The safety of LAIV in egg-allergic individuals has now been studied in more than 1,100 children and adolescents (2-18 years of age) in the United Kingdom and Canada (12)(13)(14).After careful review of recently published studies, NACI concludes that egg-allergic individuals may be vaccinated against influenza using the low ovalbumin-containing LAIV licensed for use in Canada.The full dose of LAIV may be used without prior vaccine skin test and in any settings where vaccines are routinely administered.LAIV also appears to be well tolerated in individuals with a history of stable asthma or recurrent wheeze; however, it remains contraindicated for individuals with severe asthma (defined as currently on oral or high-dose inhaled glucocorticosteroids or active wheezing) or for those with medically-attended wheezing in the seven days prior to immunization.
The literature review on the safety of LAIV in egg-allergic individuals and updated NACI recommendation on the administration of LAIV to egg-allergic individuals are published in an Addendum to the 2016-2017 Statement (5).

Updated NACI recommendations for the use of LAIV in children 2 -17 years of age
After careful review of available studies from the last several influenza seasons, NACI concludes that the current evidence is consistent with LAIV's providing comparable protection against influenza to that afforded by inactivated influenza vaccine in various jurisdictions and has revised its recommendations on the use of influenza vaccine in children 2-17 years of age: 1.In children without contraindications to the vaccine, any of the following vaccines can be used: quadrivalent LAIV, quadrivalent inactivated influenza vaccine (QIV) or TIV.
2. The current evidence does not support a recommendation for the preferential use of LAIV in children and adolescents 2-17 years of age.
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 continues to recommend that a quadrivalent formulation of influenza vaccine be used in children and adolescents 2-17 years of age.If a quadrivalent vaccine is not available, TIV should be used.
The observational study data reviewed highlight the challenge in interpreting the VE of LAIV and inactivated influenza vaccine when point estimates by influenza subtype are derived based on small sample sizes associated with wide confidence intervals.Therefore, in making its recommendation, NACI recognizes the need to continue to monitor the data on the VE of LAIV closely by influenza subtype and the relative effectiveness of LAIV compared to inactivated influenza vaccine.NACI has identified the need for further research to address current knowledge gaps: 3. NACI strongly encourages further multidisciplinary (e.g., epidemiology, immunology, virology) research to investigate the reasons for the discordant 2015-2016 VE estimates between studies and explanations for poor LAIV effectiveness against A(H1N1)pdm09 reported in some studies.
4. NACI strongly recommends that sufficient resources be provided to enhance influenza-related research and sentinel surveillance systems in Canada to improve the evaluation of influenza vaccine efficacy and effectiveness to provide the best possible evidence for Canadian influenza vaccination programs and recommendations.
Further details and rationale in support of the updated NACI recommendations on the use of LAIV in children 2-17 years of age are published in an Addendum to the 2016-2017 Statement (6).

ADVISORY COMMITTEE STATEMENT
Summary of NACI recommendations for the use of influenza vaccines for the 2016-2017 influenza season NACI continues to recommend influenza vaccination for all individuals aged six months and older, with particular focus on people at high risk of influenza-related complications or hospitalization, people capable of transmitting influenza to those at high risk and others as indicated in Table 1.
Recommended influenza vaccine options by specific age and risk groups and dosage and route of administration by age are summarized in Tables 2 and 3, respectively.

•
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 of influenza complications.• Household contacts (adults and children) of individuals at high risk of influenza-related complications (whether or not the individual at high risk has been immunized): -household contacts of individuals at high risk, as listed in the section above, -household contacts of infants under six months of age as these infants are at high risk of complications from influenza but cannot receive influenza vaccine, and members of a household expecting a newborn during the influenza season.• Those providing regular child care to children 59 months of age and younger, whether in or out of the home.• Those who provide services within closed or relatively closed settings to persons at high risk (e.g., crew on a ship).

Others
• People who provide essential community services.
• People in direct contact during culling operations with poultry infected with avian influenza.Pregnant women

• TIV • QIV
LAIV is not recommended because of the theoretical risk to the fetus from administering a live virus vaccine.
Abbreviations: ATIV, adjuvanted trivalent inactivated influenza vaccine; LAIV, live attenuated influenza vaccine (quadrivalent formulation); QIV, quadrivalent inactivated influenza vaccine; TIV, trivalent inactivated influenza vaccine1 Updated recommendations noted in bold 2 An individual with severe asthma is defined as someone who is currently on oral or high-dose inhaled glucocorticosteriods, is active wheezing, or has had medically-attended wheezing in the seven days prior to vaccination

Conclusion
NACI continues to recommend annual influenza vaccination for all individuals aged six months and older (noting product-specific age indications and contraindications), with particular focus on people at high risk of influenza-related complications or hospitalization, including all pregnant women, people capable of transmitting influenza to those at high risk and others as indicated.
Suggested citation: Gemmill I, Zhao L, and Cochrane L, on behalf of the National Advisory Committee on Immunization (NACI).Summary of the National Advisory Committee on Immunization (NACI) Statement on Seasonal Influenza Vaccine for 2016-2017.Can Comm Dis Rep 2016;42:188-92.

Table 1 :
Groups for whom influenza vaccination is particularly recommended1

Table 2 :
Choice of influenza vaccine for selected age and risk groups (for persons without a contraindication to the vaccine)1

Table 3 :
Recommended influenza vaccine dosage and route, by age, for the 2016-2017 influenza season Abbreviations: IM, intramuscular; IN, intranasal; LAIV, live attenuated influenza vaccine (quadrivalent formulation); QIV, quadrivalent inactivated influenza vaccine; TIV, trivalent inactivated influenza vaccine 1 Influvac ® 18 years and older, Fluviral ® six months and older, Agriflu ® six months and older, Vaxigrip ® six months and older, Fluzone ® six months and older, Fluzone ® High-Dose 65 years and older, Flulaval ® Tetra six months and older, Fluzone ® Quadrivalent six months and older2This information differs from the product monograph3Children six months to less than nine years of age who have never received the seasonal influenza vaccine require two doses of influenza vaccine, with a minimum interval of four weeks between doses.Eligible children less than nine years of age who have properly received one or more doses of seasonal influenza vaccine in the past should receive one dose per influenza vaccination season thereafter