Canada's National Advisory Committee on immunization: Adaptations and challenges during the COVID-19 pandemic.

The COVID-19 pandemic has challenged traditional vaccine guidance infrastructure and frameworks, and added urgency and complexity to the operation of National Immunization Technical Advisory Groups (NITAGs). Canada's National Advisory Committee on Immunization (NACI) provides immunization guidance to the Public Health Agency of Canada (PHAC) who publicly shares expert and evidence-informed guidance with Canadian provinces and territories. Throughout the pandemic, NACI and PHAC implemented many adaptations to meet urgent needs for pandemic vaccine guidance. In this paper, we describe: structural adaptations in response to the accelerated pace and amount of work required to issue recommendations that were timed around product authorizations and dynamic epidemiology; technical adaptations in response to rapidly evolving evidence of variable quality which required close monitoring, and which promoted reliance on basic vaccine principles due to incomplete direct evidence; the need to provide nimble advice (e.g., off-label recommendations, preferential recommendations); communications adaptations (e.g. identify sustainable spokespeople for the committee, receive stakeholder feedback, and ensure urgent nuanced advice was communicated to a diverse audience); and research adaptations focussing on solutions to constrained supply (e.g. prioritisation, extended intervals, and heterologous schedules). The early pandemic vaccine experience has created a roadmap of lessons and adaptations that should be leveraged in future pandemic vaccine programs, and has highlighted the essential role of NITAGs to complement regulatory structures during pandemics to ensure timely, impactful, and evidence-informed public health vaccine guidance.

Summary of the National Advisory Committee on Immunization (NACI) Statement-Recommendations on Fractional Influenza Vaccine Dosing in the Event of a Shortage: Pandemic preparedness.

Background: At the commencement of a pandemic, it is important to consider the impact of respiratory infections on the health system and the possibility of vaccine shortages due to increased demand. In the event of an influenza vaccine shortage, a strategy for administration of fractional influenza vaccine doses might be considered. This article reviews the available evidence for efficacy, effectiveness, immunogenicity and safety of fractional influenza vaccine dosing, and summarizes the National Advisory Committee on Immunization (NACI) recommendations on fractional dosing strategies by public health programs in Canada. Methods: Two rapid literature reviews were undertaken to evaluate the efficacy, effectiveness, immunogenicity and safety of fractional influenza vaccine dosing via the intramuscular or intradermal route. The NACI evidence-based process was used to assess the quality of eligible studies, summarize and analyze the findings, and apply an ethics, equity, feasibility and acceptability lens to develop recommendations. Results: There was limited evidence for the effectiveness of fractional influenza vaccine dosing. Fractional dosing studies were primarily conducted in healthy individuals, mainly young children and infants, with no underlying chronic conditions. There was fair evidence for immunogenicity and safety. Feasibility issues were identified with intradermal use in particular. Conclusion: NACI recommended that, in the event of a significant population-level shortage of influenza vaccine, a full-dose influenza vaccine should continue to be used, and existing vaccine supply should be prioritized for those considered to be at high risk or capable of transmitting to those at high risk of influenza-related complications or hospitalizations. NACI recommended against the use of fractional doses of influenza vaccine in any population.

Risk of transmission of respiratory viruses during aerosol-generating medical procedures (AGMPs) revisited in the COVID-19 pandemic: a systematic review.

BACKGROUND: In many jurisdictions healthcare workers (HCWs) are using respirators for aerosol-generating medical procedures (AGMPs) performed on adult and pediatric populations with all suspect/confirmed viral respiratory infections (VRIs). This systematic review assessed the risk of VRIs to HCWs in the presence of AGMPs, the role respirators versus medical/surgical masks have on reducing that risk, and if the risk to HCWs during AGMPs differed when caring for adult or pediatric patient populations. MAIN TEXT: We searched MEDLINE, EMBASE, Cochrane Central, Cochrane SR, CINAHL, COVID-19 specific resources, and MedRxiv for English and French articles from database inception to September 9, 2021. Independent reviewers screened abstracts using pre-defined criteria, reviewed full-text articles, selected relevant studies, abstracted data, and conducted quality assessments of all studies using the ROBINS-I risk of bias tool. Disagreements were resolved by consensus. Thirty-eight studies were included; 23 studies on COVID-19, 10 on SARS, and 5 on MERS/ influenza/other respiratory viruses. Two of the 16 studies which assessed associations found that HCWs were 1.7 to 2.5 times more likely to contract COVID-19 after exposure to AGMPs vs. not exposed to AGMPs. Eight studies reported statistically significant associations for nine specific AGMPs and transmission of SARS to HCWS. Intubation was consistently associated with an increased risk of SARS. HCWs were more likely (OR 2.05, 95% CI 1.2-3.4) to contract human coronaviruses when exposed to an AGMP in one study. There were no reported associations between AGMP exposure and transmission of influenza or in a single study on MERS. There was limited evidence supporting the use of a respirator over a medical/surgical mask during an AGMP to reduce the risk of viral transmission. One study described outcomes of HCWs exposed to a pediatric patient during intubation. CONCLUSION: Exposure to an AGMP may increase the risk of transmission of COVID-19, SARS, and human coronaviruses to HCWs, however the evidence base is heterogenous and prone to confounding, particularly related to COVID-19. There continues to be a significant research gap in the epidemiology of the risk of VRIs among HCWs during AGMPs, particularly for pediatric patients. Further evidence is needed regarding what constitutes an AGMP.

Summary of the National Advisory Committee on Immunization (NACI) Rapid Response: Updated interim guidance on Imvamune in the context of ongoing monkeypox outbreaks.

Background: During the period of monkeypox community transmission and restricted vaccine supply in the summer of 2022, Canadian provinces and territories and a number of vaccine stakeholders indicated the need for consistent national guidance on pre-exposure vaccination (including the identification of priority populations for pre-exposure vaccination programs) and guidance on the potential use of dose-sparing strategies. Methods: The National Advisory Committee on Immunization (NACI) High Consequence Infectious Disease Working Group reviewed data on the status of the monkeypox outbreak along with additional published and non-published evidence regarding the safety, immunogenicity and protection offered by Imvamune®. NACI approved updated recommendations on September 16, 2022, and on September 23, 2022 it released updated interim guidance on the use of Imvamune in the context of the ongoing monkeypox outbreak. Results: During periods of adequate vaccine supply, NACI recommended that Imvamune pre-exposure vaccination should be offered as a two-dose primary series, with at least 28 days between the two sub-cutaneous doses. When supply is limited, guidance was provided for the use of dose sparing strategies, including extended dosing intervals and fractional intradermal dosing to maximize vaccine coverage for those at highest risk of exposure to the monkeypox virus. Conclusion: The updated NACI recommendations provide additional guidance on the use of Imvamune for the management of the 2022 monkeypox outbreak in Canada and may be considered to maximize vaccine coverage in outbreak settings when supply is limited.

Summary of the NACI Supplemental Statement on Mammalian Cell Culture-Based Influenza Vaccines.

BACKGROUND: Mammalian cell culture-based technology is an innovative technique for influenza vaccine manufacturing that may be a valuable alternative to overcome some of the problems and vulnerabilities associated with conventional egg-based influenza vaccine production. Flucelvax® Quad (Seqirus, Inc.) is the first and only mammalian cell culture-based quadrivalent inactivated, subunit influenza vaccine (IIV4-cc) authorized for adult and pediatric use in Canada. The National Advisory Committee on Immunization (NACI) has not previously made a recommendation on cell culture-based influenza vaccines in any population. OBJECTIVE: To review the available evidence for the efficacy, effectiveness, immunogenicity, and safety of IIV4-cc, and to summarize the NACI recommendation regarding the use of Flucelvax Quad in Canada in adults and children. METHODS: A systematic literature review on the vaccine efficacy, effectiveness, immunogenicity and safety of IIV4-cc in persons four years of age and older was performed. The systematic review's methodology was specified a priori in a written protocol. The NACI evidence-based process was used to assess the quality of eligible studies, summarize and analyze the findings, and develop a recommendation regarding the use of Flucelvax Quad in adults and children. The proposed recommendation was then considered and approved by NACI in light of the available evidence. RESULTS: Thirteen eligible studies were included in the evidence synthesis. In the four observational studies that assessed vaccine effectiveness of IIV4-cc, there were some data indicating potentially improved protection against influenza compared to conventional egg-based quadrivalent inactivated influenza vaccines (IIV4) or trivalent inactivated influenza vaccine (IIV3), particularly against A(H3N2) virus infection. There was also some evidence that IIV4-cc may be more effective than egg-based trivalent or quadrivalent influenza vaccines against non-laboratory confirmed influenza-related outcomes, but there is insufficient evidence for laboratory-confirmed outcomes. Two randomized controlled trials assessed the immunogenicity and safety of IIV4-cc compared with mammalian cell culture-based trivalent inactivated, subunit influenza vaccine (IIV3-cc). The IIV4-cc was well-tolerated and the reported solicited local and systemic adverse events were generally mild to moderate in intensity, self-limited and did not precipitate sequelae. One clinical review of cases and six peer-reviewed randomized controlled trials (four in adults and two in children) that reported on the safety of IIV3-cc were included in the review. The evidence on immunogenicity and safety was consistent across these studies and showed that there was no significant difference in adults and children four years of age and older who had received IIV3-cc or an egg-based IIV3. CONCLUSION: NACI concluded that there is fair evidence (Grade B Evidence) that Flucelvax Quad is effective, safe, and has non-inferior immunogenicity to comparable vaccines, based on direct evidence in adults and children nine years of age and older. NACI recommends that Flucelvax Quad may be considered among the IIV4 offered to adults and children nine years of age and older (Discretionary NACI Recommendation).

Summary of the NACI systematic review and recommendation on the use of live attenuated influenza vaccine (LAIV) in HIV-infected individuals.

BACKGROUND: Annual influenza vaccination is recommended for all individuals six months of age and older, including those with HIV infection. Prior to this statement, the National Advisory Committee on Immunization (NACI) stated that live attenuated influenza vaccine (LAIV) was contraindicated for all individuals with HIV infection. The objective of this article is to update NACI's guidance on the use of LAIV for HIV-infected individuals. METHODS: A systematic literature review of the use of LAIV in individuals with HIV was undertaken. The Canadian Adverse Events Following Immunization Surveillance System was searched for reports of adverse events following vaccination with LAIV in HIV-infected individuals. NACI approved the revised recommendations. RESULTS: NACI concluded that LAIV is immunogenic in children with HIV, and available data suggest that it is safe, although data were insufficient to detect possible uncommon adverse effects. LAIV may be considered as an option for vaccination of children 2-17 years old who meet the following criteria: 1) receiving highly active antiretroviral therapy for at least four months; 2) CD4 count of 500/µL or greater if age 2-5 years, or of 200/µL or greater if age 6-17 years; and 3) HIV plasma RNA less than 10,000 copies/mL. LAIV remains contraindicated for adults with HIV because of insufficient data. Intramuscular influenza vaccination is considered the standard for children living with HIV by NACI and the Canadian Paediatric & Perinatal HIV/AIDS Research Group, particularly for those without HIV viral load suppression (i.e. plasma HIV RNA is 40 copies/mL or greater). However, if intramuscular (IM) vaccination is not accepted by the patient or substitute decision-maker, LAIV would be reasonable for children meeting the criteria listed above. CONCLUSION: LAIV may be considered as an option for annual vaccination of selected children with HIV.

Summary of the NACI Seasonal Influenza Vaccine Statement for 2020-2021.

BACKGROUND: Evidence on influenza vaccination is continually evolving. The National Advisory Committee on Immunization (NACI) provides annual recommendations to the Public Health Agency of Canada regarding the use of seasonal influenza vaccines. OBJECTIVE: To summarize NACI's recommendations regarding the use of seasonal influenza vaccines for the 2020-2021 influenza season and to highlight new and updated recommendations. METHODS: 1) To update wording on influenza vaccination of health care workers, NACI reassessed the evidence in the context of ethics and acceptability frameworks, in accordance with NACI's recently expanded mandate. 2) To provide recommendations on the use of live attenuated influenza vaccine (LAIV) in HIV-infected individuals, the Influenza Working Group developed a predefined search strategy to identify all eligible studies, then assessed the quality and summarized and analyzed the findings according to the NACI evidence-based process. NACI provided new recommendations based on assessment of the evidence. RESULTS: 1) NACI continues to recommend that health care workers and other care providers in facilities and community settings should be vaccinated annually against influenza and that this group be included among those particularly recommended to receive the influenza vaccine. 2) NACI concluded that LAIV is immunogenic in children with stable HIV infection; therefore, NACI newly recommends that LAIV may be considered as an option for children 2-17 years of age with stable HIV infection on highly active antiretroviral therapy and with adequate immune function. 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 a focus on the groups for whom influenza vaccination is particularly recommended.

Summary of the NACI Statement on the Use of Bivalent Factor H Binding Protein Meningococcal Serogroup B (MenB-fHBP) Vaccine for the Prevention of Meningococcal B Disease.

BACKGROUND: TrumenbaTM, a bivalent, factor-H binding protein meningococcal serogroup B (MenB-fHBP) vaccine was authorized for use in Canada in October 2017 for the prevention of invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup B in individuals 10-25 years of age. The National Advisory Committee on Immunization (NACI) provides recommendations regarding the use of meningococcal vaccines to the Public Health Agency of Canada. OBJECTIVE: To summarize NACI recommendations regarding the use of MenB-fHBP vaccine in Canada. METHODS: The NACI Meningococcal Disease Working Group developed a predefined search strategy to identify all eligible studies, assessed the quality of these studies, and summarized and analyzed the findings. According to the NACI evidence-based process, the working group then 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: The two serogroup B meningococcal vaccines currently authorized for use in Canada are not interchangeable as they contain different antigens and there are no published studies on the immunogenicity resulting from a vaccination series combining the two products. Following the review of evidence, NACI recommends that MenB-fHBP vaccine may be considered as an option for use in individuals 10 years of age and older in situations when a serogroup B meningococcal vaccine should be offered: 1) during serogroup B meningococcal disease outbreaks or with the emergence of hyperendemic N. meningitidis strains that are predicted to be susceptible to the vaccine; 2) for individuals who are close contacts with a case of invasive meningococcal disease caused by serogroup B N. meningitidis; 3) for individuals with underlying medical conditions that would put them at higher risk of meningococcal disease than the general population; or 4) for individuals at higher risk of exposure to serogroup B meningococcal isolates than the general population. NACI also recommends that MenB-fHBP vaccine may be considered as an option for individuals 10-25 years of age who are not at higher risk of meningococcal disease than the general population, but who wish to reduce their risk of invasive serogroup B meningococcal disease. CONCLUSION: NACI recommends immunization against serogroup B IMD for all individuals who are at a higher risk of disease due to an underlying medical condition or an increased risk of exposure. In addition to providing guidance to public health decision-makers (i.e. provinces/territories making decisions for publicly-funded immunization programs), these NACI recommendations provide information to individuals, vaccine providers and organizations about vaccines that may not currently be included in publicly funded immunization programs. NACI continues to recommend against the use of the serogroup B vaccines in routine universal immunization programs in Canada at this time.

Osteoporosis-related kyphosis and impairments in pulmonary function: a systematic review.

UNLABELLED: We conducted a systematic review to examine the relationship between osteoporotic vertebral fractures, kyphosis, and pulmonary function. Findings suggest modest but predictable declines in vital capacity related to the degree of kyphosis. However, there were only four studies, and all had significant methodologic limitations. Further high-quality research is needed. INTRODUCTION: Our objective was to systematically review the extent to which osteoporosis-related vertebral fractures and kyphosis affect pulmonary function. MATERIALS AND METHODS: We used a literature search from 1966 to 2006 (using Medline, EMBASE, and hand searches of references) for studies examining pulmonary function in patients without known lung disease who had vertebral fractures or kyphosis secondary to osteoporosis. Two reviewers independently abstracted data. Heterogeneity precluded formal meta-analysis. RESULTS: Initial searches yielded 453 articles. After applying eligibility criteria, only four case-control studies of limited quality (e.g., only one study was blinded) remained. Since 1966, only 109 patients (6 men) have been studied. All four studies reported reductions in vital capacity (VC), with values ranging from 68% to 94% of predicted values. This was quantified as a 9% reduction in predicted VC per vertebral fracture in one study. The degree of kyphosis clinically (one study) or radiographically (three studies) correlated with declines in VC; impairments were most notable at kyphotic angles>55 degrees. Statistically significant differences in percent predicted VC were obtained only when arm span or recalled height, rather than measured height, was used (two studies). CONCLUSIONS: Despite conventional teaching, the evidence relating osteoporotic vertebral fractures or kyphosis to pulmonary function is limited. On the basis of available studies, declines in VC secondary to kyphosis seem modest and directly related to the number of vertebral fractures or degree of kyphosis. Future studies need longitudinal follow-up of larger numbers of men and women, appropriate proxies for height, standardized measures for pulmonary function and kyphosis, and efforts to blind outcomes ascertainment.