The SAGE Working Group on Vaccine Hesitancy concluded that vaccine hesitancy refers to delay in acceptance or refusal of vaccination despite availability of vaccination services. Vaccine hesitancy is complex and context specific, varying across time, place and vaccines. It is influenced by factors such as complacency, convenience and confidence. The Working Group retained the term 'vaccine' rather than 'vaccination' hesitancy, although the latter more correctly implies the broader range of immunization concerns, as vaccine hesitancy is the more commonly used term. While high levels of hesitancy lead to low vaccine demand, low levels of hesitancy do not necessarily mean high vaccine demand. The Vaccine Hesitancy Determinants Matrix displays the factors influencing the behavioral decision to accept, delay or reject some or all vaccines under three categories: contextual, individual and group, and vaccine/vaccination-specific influences.

In order to gather a global picture of vaccine hesitancy and whether/how it is changing, an analysis was undertaken to review three years of data available as of June 2017 from the WHO/UNICEF Joint Report Form (JRF) to determine the reported rate of vaccine hesitancy across the globe, the cited reasons for hesitancy, if these varied by country income level and/or by WHO region and whether these reasons were based upon an assessment. The reported reasons were classified using the Strategic Advisory Group of Experts (SAGE) on Immunization matrix of hesitancy determinants (www.who.int/immunization/sage/meetings/2014/october/SAGE_working_group_revised_report_vaccine_hesitancy.pdf). Hesitancy was common, reported by >90% of countries. The list of cited reasons was long and covered 22 of 23 WHO determinants matrix categories. Even the most frequently cited category, risk- benefit (scientific evidence e.g. vaccine safety concerns), accounted for less than one quarter of all reasons cited. The reasons varied by country income level, by WHO region and over time and within a country. Thus based upon this JRF data, across the globe countries appear to understand the SAGE vaccine hesitancy definition and use it to report reasons for hesitancy. However, the rigour of the cited reasons could be improved as only just over 1/3 of countries reported that their reasons were assessment based, the rest were opinion based. With respect to any assessment in the previous five years, upper middle income countries were the least likely to have done an assessment. These analyses provided some of the evidence for the 2017 Assessment Report of the Global Vaccine Action Plan recommendation that each country develop a strategy to increase acceptance and demand for vaccination, which should include ongoing community engagement and trust-building, active hesitancy prevention, regular national assessment of vaccine concerns, and crisis response planning (www.who.int/immunization/sage/meetings/2017/october/1_GVAP_Assessment_report_web_version.pdf).

An often-stated public health comment is that “vaccination is a victim of its own success.” While the scientific and medical consensus on the benefits of vaccination is clear and unambiguous, an increasing number of people are perceiving vaccines as unsafe and unnecessary. The World Health Organization identified “the reluctance or refusal to vaccinate despite availability of vaccines” as one of the 10 threats to global health in 2019. The negative influence of anti-vaccination movements is often named as a cause of increasing vaccine resistance in the public. In this review, we give an overview of the current literature on the topic, beginning by agreeing on terminology and concepts before looking at potential causes, consequences, and impacts of resistance to vaccination.

The vaccine safety surveillance system effectively detected a very rare adverse event, narcolepsy, in subjects receiving AS03-adjuvanted A(H1N1) pandemic vaccine made using the European inactivation/purification protocol. The reports of increased cases of narcolepsy in non-vaccinated subjects infected with wild A(H1N1) pandemic influenza virus suggest a role for the viral antigen(s) in disease development. However, additional investigations are needed to better understand what factor(s) in wild influenza infection trigger(s) narcolepsy in susceptible hosts. An estimated 31 million doses of European AS03-adjuvanted A(H1N1) pandemic vaccine were used in more than 47 countries. The Canadian AS03-adjuvanted A(H1N1) pandemic vaccine was used with high coverage in Canada where an estimated 12 million doses were administered. As no similar narcolepsy association has been reported to date with the AS03-adjuvanted A(H1N1) pandemic vaccine made using the Canadian inactivation/purification protocol, this suggests that the AS03 adjuvant alone may not be responsible for the narcolepsy association. To date, no narcolepsy association has been reported with the MF59®-adjuvanted A(H1N1) pandemic vaccine. This review article provides a brief background on narcolepsy, outlines the different types of vaccine preparations including the ones for influenza, reviews the accumulated evidence for the safety of adjuvants, and explores the association between autoimmune diseases and natural infections. It concludes by assimilating the historical observations and recent clinical studies to formulate a feasible hypothesis on why vaccine-associated narcolepsy may not be solely linked to the AS03 adjuvant but more likely be linked to how the specific influenza antigen component of the European AS03-adjuvanted pandemic vaccine was prepared. Careful and long-term epidemiological studies of subjects who developed narcolepsy in association with AS03-adjuvanted A(H1N1) pandemic vaccine prepared with the European inactivation/purification protocol are needed.

• Reported to SAGE on immunization and surveillance data quality & use, October 2019. • Improvements since 2011, but gaps persist in data quality (fit-for-purpose) and use. • Improving data quality and use requires better governance, people, tools, and processes. • Better use of existing data needed to continuously improve programme performance. • Report relevant for “data-guided” implementation of the Immunization Agenda 2030.

Addressing the drivers of vaccine hesitancy and the barriers to vaccine acceptance is a complex but important task. While the percentage of hesitant does vary from country to country and in time few, if any, countries are ever free from this problem. Overcoming hesitancy requires detection, diagnosis and tailored intervention as there is no simple strategy that can address all of the barriers to vaccine acceptance. Immunization program managers and health care workers need to become adept at recognizing and tackling hesitancy in all of its incarnations if high levels of vaccine acceptance are to be achieved but must also actively support immunization acceptors in order to build and support vaccine acceptance resiliency. This paper presents evidence-informed strategies to achieve these goals.