Summary of the NACI Seasonal Influenza Vaccine Statement for 2019-2020.

BACKGROUND: Many different influenza vaccines are authorized for use in Canada and new evidence on influenza and vaccines is continually emerging. The National Advisory Committee on Immunization (NACI) provides annual recommendations regarding the use of seasonal influenza vaccines to the Public Health Agency of Canada (PHAC) for the upcoming influenza season. OBJECTIVE: To summarize NACI recommendations regarding the use of seasonal influenza vaccines for the 2019-2020 influenza season, including conclusions from reviews of evidence on 1) a new split virus quadrivalent inactivated influenza vaccine and 2) the comparative effectiveness and immunogenicity of subunit and split virus inactivated influenza vaccines in adults 65 years of age and older. METHODS: For both topics, the NACI Influenza Working Group developed a predefined search strategy to identify all eligible studies, assessed their quality, summarized and analyzed the findings and, according to the NACI evidence-based process, proposed recommendations and identified the grade of evidence that supported them. In light of the evidence, the recommendations were then considered and approved by NACI. RESULTS: NACI concluded that the new split virus quadrivalent inactivated influenza vaccine has a safety and immunogenicity profile comparable to the quadrivalent inactivated influenza vaccines already authorized for adults and children 5 years of age and older (Grade B Evidence). Therefore, NACI recommended that this new vaccine may be considered among the quadrivalent inactivated influenza vaccines offered to adults and children five years of age and older (Discretionary NACI Recommendation). However, NACI concluded that the evidence is not sufficient (Grade I Evidence) to support specific recommendations on the differential use of subunit and split virus inactivated influenza vaccines in adults 65 years of age and older. CONCLUSION: NACI continues to recommend that an age-appropriate influenza vaccine should be offered annually to anyone six months of age and older who does not have contraindications to the vaccine, with focus on the groups for whom influenza vaccination is particularly recommended. This includes people at high risk of 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.

Summary of the NACI literature review on the comparative effectiveness of subunit and split virus inactivated influenza vaccines in older adults.

BACKGROUND: Subunit and split virus inactivated influenza vaccines (IIV) are two commonly used types of seasonal influenza vaccines in Canada. The comparative effectiveness of these two formulations is particularly relevant for older adults, as older adults have reduced influenza vaccine effectiveness and experience more severe influenza than younger adults. OBJECTIVE: To compare the vaccine effectiveness and immunogenicity of unadjuvanted, standard-dose subunit IIVs versus unadjuvanted, standard-dose split virus IIVs in adults 65 years of age and older. METHODS: An a priori written protocol based on rapid review methods was developed that included studies published in 2007 or later in the EMBASE, MEDLINE and ClinicalTrials.gov databases with terms used in the objective. Due to the small number of records returned, hand searches of reference lists were completed, the publication date limit was removed, three additional databases (the Cochrane Central Register of Controlled Trials, Scopus and Web of Science) were searched, and studies including adults 60 years of age and older were included. Data from included studies were extracted into evidence tables and quality assessments were completed. The results were synthesized narratively. RESULTS: Eight eligible studies were identified. In the three studies that assessed vaccine effectiveness of subunit and split virus IIVs, there were no statistically significant differences in vaccine effectiveness in adults 65 years of age and older against laboratory-confirmed infection with any influenza virus strain, or against laboratory-confirmed infection with influenza A(H1N1), A(H3N2) or B virus, specifically. In the five studies that assessed immunogenicity, the findings were not consistent and the overall quality of immunogenicity evidence was weak. CONCLUSION: The National Advisory Committee on Immunization (NACI) concludes that there is insufficient evidence to determine significant differences in the vaccine effectiveness or immunogenicity of unadjuvanted, standard-dose subunit and split virus IIVs in adults 65 years of age and older (Grade I evidence).

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 over; 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.

Summary of the National Advisory Committee on Immunization (NACI) Statement on Seasonal Influenza Vaccine for 2015-2016.

BACKGROUND: The National Advisory Committee on Immunization (NACI) provides the Public Health Agency of Canada with ongoing and timely medical, scientific, and public health advice relating to immunization. OBJECTIVE: To summarize the update of the 2015-2016 recommendations by NACI regarding the use of seasonal influenza vaccines. METHODS: Annual influenza vaccine recommendations are developed by the Influenza Working Group for consideration by NACI, based on NACI's evidence-based process for developing recommendations, and includes: 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. RESULTS: NACI continues to recommend influenza vaccination for all individuals aged 6 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. For the 2015-2016 influenza season, the Statement has been updated to identify children and adolescents with neurologic or neurodevelopment conditions as a group at high risk for influenza-related complications or hospitalization. Several changes to product availability in Canada have also been noted. A new adjuvanted, trivalent influenza vaccine (Fluad Pediatric™ [Novartis]) will be available for use in children aged 6 to <24 months. The recommended choice of product for this age group, however, is quadrivalent inactivated influenza vaccine (QIV), because children are more likely to be affected by influenza B, and the QIV provides broader protection against both lineages of influenza B. If QIV is not available, either unadjuvanted or adjuvanted trivalent inactivated influenza vaccine (TIV) should be used. Only the quadrivalent formulation of the live attenuated influenza vaccine (LAIV) (FluMist® Quadrivalent [AstraZeneca]) will be available, and the recommendation for preferential use of LAIV in children 2 to 17 years of age who do not have contraindications to this vaccine remains unchanged following a review of information pertaining to reports of decreased effectiveness of LAIV in the United States during the 2013-2014 season. Finally, the intradermal trivalent influenza vaccine (Intanza® [Sanofi Pasteur]) will no longer be available for use in Canada. Other updates to the Statement include additional information reaffirming the safety of LAIV use in children with cystic fibrosis who are not considered immunosuppressed or receiving immunosuppressive treatment, as well as a revised definition for oculo-respiratory syndrome which, when it occurs, should be reported as an adverse event following immunization (AEFI) to local public health officials. CONCLUSION: Vaccination is the safest, longest lasting and most effective way to prevent influenza.

Vaccines for adults: The time has come.

The benefits of vaccines for adults have been underappreciated because of the focus on childhood vaccines. However, precisely because of the success of immunization programs for children, most deaths from vaccine-preventable diseases now occur amongst adults. Tetanus boosters will help to maintain Canada's low tetanus rates and pertussis boosters for adults are now available. Human papilloma virus vaccine may be indicated in some older adults. Hepatitis A and B vaccines may be indicated if there is occupational, travel or lifestyle risk. Pneumococcal and zoster vaccines are recommended in those over 65 years of age, and all adults benefit from annual influenza vaccination. A systematic approach to immunizing adults would assist in ensuring that all who are eligible for specific vaccines are offered them. This approach would include promoting routine immunization as a fundamental part of every patient encounter and the use of tools, such as the Adult Immunization Questionnaire and the Adult Immunization Wallet Card. By investing in these strategies, the health of adults can be improved significantly.

Updates to the Canadian Immunization Guide: March 2014 to March 2015.

The National Advisory Committee on Immunization (NACI) develops recommendations for the use of vaccines for Canadians, which are summarized in the Canadian Immunization Guide (the Guide) and which is updated on a regular basis. Between March 2014 and February 2015 recommendations on five vaccines have been issued. Updates to the Guide include recommendations made for the alternative dosing administration of the human papillomavirus (HPV) vaccine in adolescents, timing of varicella zoster immune globulin (VarIg) following exposure to varicella, and the meningococcal and quadrivalent influenza vaccines, recently authorized for use in Canada. A change in recommendations for the use of pneumococcal vaccines in adults and individuals with asthma has also been made. The chapter on tick-borne encephalitis vaccine has now been removed from the Guide as this vaccine is no longer available in Canada.

Interferon-gamma release assays piloted as a latent tuberculous infection screening tool in Canadian federal inmates.

BACKGROUND: Interferon-gamma release assays (IGRAs) may be useful in diagnosing latent tuberculous infection (LTBI) in inmates; however, published experience in these settings is limited. OBJECTIVE: To identify variables associated with IGRA positivity among Canadian federal inmates with positive tuberculin skin test (TST) results. DESIGN: On intake, TST-positive (≥10 mm) inmates were offered an IGRA (QuantiFERON(®)-TB Gold), and demographic and historical data were collected. IGRA-positive and -negative inmates were compared using the χ(2) test and multivariable logistic regression; the final model's goodness of fit was assessed using Hosmer-Lemeshow test and area under the receiver operating characteristic curve (AUC). RESULTS: Of 96 TST-positive inmates, 31 (32.3%) were IGRA-positive. Variables associated with positive IGRA were age >45 years (11/20 vs. 20/75, P = 0.016) and previous LTBI treatment (9/20 vs. 13/55, P = 0.032) in univariate analysis, and being from a country with a moderate or high estimated tuberculosis (TB) incidence (OR 3.5, 95%CI 1.3-9.4, P = 0.013) and absence of bacille Calmette-Guérin (BCG) vaccination (OR 3.3, 95%CI 1.2-9.0, P = 0.017) in multivariable analysis. The data fit the model well, classifying the group better than chance alone (AUC 0.67, P = 0.007). CONCLUSION: High discordance with TST, particularly among BCG-vaccinated inmates and those from low TB incidence countries, suggest that IGRA may be useful in Canadian federal penitentiary screening programmes.

The National Advisory Committee on Immunization (NACI): A celebration of fifty years of service.

The National Advisory Committee on Immunization (NACI) celebrates its fiftieth anniversary in October 2014. This paper outlines the history of NACI and its activities over the past 50 years. After its formation in 1964, NACI undertook the development of guidance for the few vaccines that were approved at that time, including polio, measles, tetanus, pertussis, diphtheria and smallpox. Although the Committee has evolved over the years, its focus has remained on providing guidance on an ever-increasing number of products: twenty-four, according to the recent updates to the Canadian Immunization Guide. With the changing vaccine landscape, including immunization programs and practices, the membership of the Committee has evolved to include expanded expertise, such as immunology. The work of the Committee has had to adapt, with more complex and extensive evidence and the establishment of a published evidence-based methodology. Over the past 50 years, the success and accomplishments of NACI have been in large part due to the efforts of its chair and members, who have dedicated countless hours of work to committee activities and products. NACI's Technical advisory groups are recognized globally as a valuable resource, benefiting immunization practices and programs across Canada and internationally. NACI is a committee of which PHAC and indeed Canada can be truly proud.

Clinicians' opinions on new vaccination programs implementation.

In Canada, several new vaccines were recently approved for clinical use or are expected to be soon. Decision-makers are faced with the choice whether or not to include these vaccines in publicly funded vaccination programs. The aim of this study was to assess Canadian pediatricians' and family physicians' opinions regarding 7 new vaccines, and perceived priority for the introduction of new programs. A self-administered, anonymous, mail-based questionnaire was sent during fall 2009 to a random sample of 1182 family physicians and to all 1852 Canadian pediatricians. Responses to 8 statements regarding frequency and severity of the diseases, efficacy and safety of the vaccines as well as feasibility of immunization programs were used to calculate priority scores to rank the 7 potential new vaccination programs (calculated scores ranging from 0 to 100). Overall response rate was 43%. The majority of respondents perceived the health and economic burden of diseases prevented by the seven new vaccines as important and considered new vaccines to be safe and effective. More than 90% of physicians strongly agreed or agreed that the new vaccines would be or are currently well accepted by the public and by the health professionals who administer vaccines, except for the HPV and rotavirus vaccines (respectively 30% and 29% strongly agreed or agreed). Mean priority scores were: 77.4 out of 100 for the measles, mumps, rubella and varicella (MMRV) combined vaccine; 75.6 for the hexavalent (DTaP-IPV-Hib-HBV) vaccine; 73.1 for the new pneumococcal conjugate vaccines; 69.8 for the meningococcal ACYW135; 68.9 for the combined hepatitis A and B; 63.5 for the human papillomavirus vaccine and 56.9 for the rotavirus vaccine. Health professionals' opinion is an important element to consider in the decision-making process regarding implementation of new immunization programs. Without health professional support, the introduction of a new vaccination program may be unsuccessful. In this study, the MMRV and the hexavalent (DTaP-IPV-Hib-HBV) vaccines received the highest ratings.

Canadian paediatricians' opinions on rotavirus vaccination.

Rotavirus is the leading cause of dehydration and hospitalization due to gastroenteritis (GE) in young children. Almost all children are affected by the age of 5 years. Two safe and effective rotavirus vaccines are available for clinical use in Canada. In the context where rotavirus vaccination is recommended, but not publicly funded, we have assessed paediatricians' knowledge, attitudes and beliefs (KAB) regarding rotavirus disease and its prevention by vaccination. A self-administered anonymous questionnaire based upon the Health Belief Model and the Analytical framework for immunization programs was mailed to all 1852 Canadian paediatricians. The response rate was 50%. The majority of respondents rated consequences of rotavirus infection for young patients as moderate. Sixty-six percent considered that rotavirus disease occur frequently without vaccination and 62% estimated that the disease generates a significant economic burden. Sixty-nine percent of respondents considered rotavirus vaccines to be safe and 61%, to be effective. The reduction of severe GE cases was seen as the main benefit of rotavirus vaccination, while the risk of adverse events was the principal perceived barrier. Fifty-three percent (53%) indicated a strong intention to recommend rotavirus vaccines. In multivariate analysis, main determinant of paediatricians' intention to recommend rotavirus vaccines was the perceived health and economic burden of rotavirus diseases (partial R(2)=0.49, p<0.0001). More than half of surveyed paediatricians were willing to recommend rotavirus vaccines to their patients, but the proportion of respondents who had a strong intention to do so remains low when compared to several other new vaccines. As with other new vaccines, rotavirus vaccine uptake risks to remain low in Canada as long as it is not publicly funded.

Economic evaluation of a new acellular vaccine for pertussis in Canada.

OBJECTIVE: Pertussis is a highly contagious infection affecting mainly children. Acellular pertussis vaccines were recently introduced in Canada based on evidence of improved safety and efficacy over whole cell vaccines, the current standard of care. The following study reports the economic impact of replacing the whole cell vaccine (wP) by a new acellular vaccine (aP) in the Ontario pertussis immunisation programme. DESIGN: For a hypothetical cohort of 100,000 children from birth to the age of 8 years, the costs and consequences of pertussis vaccination with either aP or wP were compared. A decision analytical model was constructed for vaccine delivery, treatment of pertussis cases and vaccine adverse events, with analyses from the viewpoints of the Ontario Ministry of Health and society. MAIN OUTCOME MEASURES AND RESULTS: The main outcomes were expected number of pertussis cases, hospitalisations, and workdays lost by parents. Data on vaccine effectiveness, pertussis incidence, and other parameters used in the model were from published literature. Costs were discounted at 5%, and extensive sensitivity analyses were undertaken. Over 8 years, in a cohort of 100,000 children, the introduction of aP would prevent 10,500 cases of pertussis, avoiding 504 hospital admissions and 73,500 days of work absence. For Ontario, healthcare cost savings over the same period would amount to 275,585 Canadian dollars ($Can), and societal savings to $Can9,752,864

Pooling of urine specimens for PCR testing: a cost saving strategy for Chlamydia trachomatis control programmes.

OBJECTIVES: To evaluate pooling of first catch urine (FCU) specimens as a cost effective strategy for chlamydia testing. METHODS: Mock specimens were pooled with and without dilution to determine optimal pool size and ease of work flow. The performance of the Amplicor Chlamydia trachomatis PCR assay on pooled specimens was compared with individual testing using 370 FCU specimens from asymptomatic men presenting to an STD clinic. Cost savings associated with pooling were estimated. RESULTS: Using mock specimens, the sensitivity and specificity of the Amplicor PCR assay were not affected by pool sizes of two and five, but at a pool size of 10 decreased sensitivity due to inhibition was observed in one of five mock pools when the pooling method which involved no dilution was used. Archived FCU specimens from a study of 370 asymptomatic men were combined consecutively into 74 pools of five and tested by PCR. Of the 18 pools that contained positive specimens, 17 were PCR positive. Compared with testing FCU specimens individually, pooling resulted in a sensitivity of 95%, specificity of 100%, and a cost savings of 57% based on reduced number of tests required. CONCLUSION: Depending on the prevalence of infection, pooling of FCU specimens for PCR testing may result in cost savings compared with testing specimens individually. Further evaluations to validate this strategy using fresh FCU specimens are needed.

Noninvasive screening for genital chlamydial infections in asymptomatic men: Strategies and costs using a urine PCR assay.

OBJECTIVE: To evaluate cost saving strategies to screen for genital chlamydial infection in men using polymerase chain reaction (PCR) technology. METHODS: Men with no urethral symptoms presenting to a sexually transmitted disease (STD) clinic were recruited. Study participants underwent a questionnaire interview. Urethral swabs were taken to perform a smear for polymorphonuclear leucocytes (PMN) and for the detection of Chlamydia trachomatis by culture and PCR. First-catch urine was collected for a leukocyte esterase test (LET) and PCR. RESULTS: C trachomatis infection was detected in 36 of 463 (7.8%) men. LET and PMN were positive in 10 (28%) and 12 (33%) infected men, respectively. Risk factors for chlamydial infection were younger than age 25 years, LET-positive, PMN-positive and STD contact (P<0.001). The direct cost of genital chlamydial infection in men in Canada has been previously estimated at $381/case. Based on a sensitivity of 90% for urine PCR, the estimated direct cost of testing all participants to detect 32 cases was $453/case. Using risk factors recommended in the Canadian STD Guidelines (age younger than 25 years, new partner, STD contact or unprotected sex), the same number of cases would have been detected by testing only 384 men at $376/case. Using age younger than 25 years or STD contact as the screening criterion, 78% of those infected would have been detected at $259/case, and no new cases would have been detected by adding LET-positive or PMN-positive as risk factors. CONCLUSION: Targeted screening for chlamydial infection using urine PCR assay and risk factors recommended in the Canadian guidelines could substantially reduce the cost of screening at a STD clinic setting. LET and PMN smear did not appear to be useful indicators of chlamydial infection in this population.

Diagnosis of Chlamydia trachomatis infections in asymptomatic men and women by PCR assay.

A PCR assay was evaluated for its ability to detect genital chlamydial infection in asymptomatic men and women. Urethral swab specimens were collected from 472 men for culture and PCR assay, and first-void urine (FVU) specimens were collected from 379 of these men for enzyme immunoassay (EIA) and PCR assay. Cervical swab specimens were collected from 242 women for culture, EIA, and PCR assay. Patients were considered infected if they were culture positive or positive by PCR with both plasmid- and major outer membrane protein-based primers. By using this extended "gold standard," the prevalence of infection in this population was 7.6% for men and 7.9% for women. For men, the sensitivities of urethral swab specimen culture and PCR and FVU specimen EIA and PCR were 61, 72, 55, and 91%, respectively. All assays had specificities of > or = 99.8%. The positive and negative predictive values for PCR testing of FVU specimens were 100 and 99.4%, respectively, compared with values of 96.3 and 97.8%, respectively, for PCR of urethral swab specimens. The sensitivities of cervical swab specimen culture and PCR testing were 42 and 90%, respectively, with corresponding specificities of 100 and 99.3%. All cervical swabs were negative by EIA. Molecular techniques such as PCR assays are valuable tools for the detection of symptomatic genital chlamydial infection. In particular, PCR assays of FVU specimens from men offer a highly sensitive, noninvasive screening tool that will likely improve patient compliance for diagnostic testing.

Evaluation and follow-up of infectious tuberculosis at the University of Ottawa.

A case of active infectious pulmonary tuberculosis (tb) in a recent immigrant to Canada was identified at the University of Ottawa. The student was attending classes regularly and coughing for six months before the diagnosis of infectious pulmonary tb was made. Investigation carried out by the Ottawa-Carleton Health Department identified 871 student contacts. Of the 871 contacts, 773 (89%) were available for testing and follow-up. Initial skin testing with purified protein derivative (ppd) was positive in 149 contacts. Of the 602 contacts testing negative initially 399 (66%) returned for 12-week retesting. Eleven skin test converters were identified. All 160 contacts with positive ppd had negative chest x-ray and were given isoniazid prophylaxis for six months. The estimated cost of the process of contact tracing, testing, follow-up and treatment was $34,036. Although pre-immigration screening policies for tb do exist, additional pre- and postimmigration measures could help in the early detection of active tb and the prevention of its spread.