Heidi J. Larson

Addressing the vaccine confidence gap.

Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK (H J Larson PhD); Department of Paediatrics, College of Physicians and Surgeons, Columbia University, New York, NY, USA (Prof L Z Cooper MD); National Institute for Health and Welfare (THL), Helsinki, Finland (J Eskola MD); Department of Paediatrics, Duke University, Durham, NC, USA (Prof S L Katz MD); Government Aff airs and Policy, Johnson & Johnson, New Brunswick, NJ, USA; (S Ratzan MD); and Journal New Decade of Vaccines 5Vaccines--often lauded as one of the greatest public health interventions--are losing public confidence. Some vaccine experts have referred to this decline in confidence as a crisis. We discuss some of the characteristics of the changing global environment that are contributing to increased public questioning of vaccines, and outline some of the specific determinants of public trust. Public decision making related to vaccine acceptance is neither driven by scientific nor economic evidence alone, but is also driven by a mix of psychological, sociocultural, and political factors, all of which need to be understood and taken into account by policy and other decision makers. Public trust in vaccines is highly variable and building trust depends on understanding perceptions of vaccines and vaccine risks, historical experiences, religious or political affiliations, and socioeconomic status. Although provision of accurate, scientifically based evidence on the risk-benefit ratios of vaccines is crucial, it is not enough to redress the gap between current levels of public confidence in vaccines and levels of trust needed to ensure adequate and sustained vaccine coverage. We call for more research not just on individual determinants of public trust, but on what mix of factors are most likely to sustain public trust. The vaccine community demands rigorous evidence on vaccine efficacy and safety and technical and operational feasibility when introducing a new vaccine, but has been negligent in demanding equally rigorous research to understand the psychological, social, and political factors that affect public trust in vaccines.

Coming to terms with complexity : a call to action for HIV prevention

A quarter of a century of AIDS responses has created a huge body of knowledge about HIV transmission and how to prevent it, yet every day, around the world, nearly 7000 people become infected with the virus. Although HIV prevention is complex, it ought not to be mystifying. Local and national achievements in curbing the epidemic have been myriad, and have created a body of evidence about what works, but these successful approaches have not yet been fully applied. Essential programmes and services have not had sufficient coverage; they have often lacked the funding to be applied with sufficient quality and intensity. Action and funding have not necessarily been directed to where the epidemic is or to what drives it. Few programmes address vulnerability to HIV and structural determinants of the epidemic. A prevention constituency has not been adequately mobilised to stimulate the demand for HIV prevention. Confident and unified leadership has not emerged to assert what is needed in HIV prevention and how to overcome the political, sociocultural, and logistic barriers in getting there. We discuss the combination of solutions which are needed to intensify HIV prevention, using the existing body of evidence and the lessons from our successes and failures in HIV prevention.

Changes in health in England, with analysis by English regions and areas of deprivation, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Summary Background In the Global Burden of Disease Study 2013 (GBD 2013), knowledge about health and its determinants has been integrated into a comparable framework to inform health policy. Outputs of this analysis are relevant to current policy questions in England and elsewhere, particularly on health inequalities. We use GBD 2013 data on mortality and causes of death, and disease and injury incidence and prevalence to analyse the burden of disease and injury in England as a whole, in English regions, and within each English region by deprivation quintile. We also assess disease and injury burden in England attributable to potentially preventable risk factors. England and the English regions are compared with the remaining constituent countries of the UK and with comparable countries in the European Union (EU) and beyond. Methods We extracted data from the GBD 2013 to compare mortality, causes of death, years of life lost (YLLs), years lived with a disability (YLDs), and disability-adjusted life-years (DALYs) in England, the UK, and 18 other countries (the first 15 EU members [apart from the UK] and Australia, Canada, Norway, and the USA [EU15+]). We extended elements of the analysis to English regions, and subregional areas defined by deprivation quintile (deprivation areas). We used data split by the nine English regions (corresponding to the European boundaries of the Nomenclature for Territorial Statistics level 1 [NUTS 1] regions), and by quintile groups within each English region according to deprivation, thereby making 45 regional deprivation areas. Deprivation quintiles were defined by area of residence ranked at national level by Index of Multiple Deprivation score, 2010. Burden due to various risk factors is described for England using new GBD methodology to estimate independent and overlapping attributable risk for five tiers of behavioural, metabolic, and environmental risk factors. We present results for 306 causes and 2337 sequelae, and 79 risks or risk clusters. Findings Between 1990 and 2013, life expectancy from birth in England increased by 5·4 years (95% uncertainty interval 5·0–5·8) from 75·9 years (75·9–76·0) to 81·3 years (80·9–81·7); gains were greater for men than for women. Rates of age-standardised YLLs reduced by 41·1% (38·3–43·6), whereas DALYs were reduced by 23·8% (20·9–27·1), and YLDs by 1·4% (0·1–2·8). For these measures, England ranked better than the UK and the EU15+ means. Between 1990 and 2013, the range in life expectancy among 45 regional deprivation areas remained 8·2 years for men and decreased from 7·2 years in 1990 to 6·9 years in 2013 for women. In 2013, the leading cause of YLLs was ischaemic heart disease, and the leading cause of DALYs was low back and neck pain. Known risk factors accounted for 39·6% (37·7–41·7) of DALYs; leading behavioural risk factors were suboptimal diet (10·8% [9·1–12·7]) and tobacco (10·7% [9·4–12·0]). Interpretation Health in England is improving although substantial opportunities exist for further reductions in the burden of preventable disease. The gap in mortality rates between men and women has reduced, but marked health inequalities between the least deprived and most deprived areas remain. Declines in mortality have not been matched by similar declines in morbidity, resulting in people living longer with diseases. Health policies must therefore address the causes of ill health as well as those of premature mortality. Systematic action locally and nationally is needed to reduce risk exposures, support healthy behaviours, alleviate the severity of chronic disabling disorders, and mitigate the effects of socioeconomic deprivation. Funding Bill & Melinda Gates Foundation and Public Health England.

Protecting Public Trust in Immunization

Public trust in the safety and efficacy of vaccines is one key to the remarkable success of immunization programs within the United States and globally. Allegations of harm from vaccination have raised parental, political, and clinical anxiety to a level that now threatens the ability of children to receive timely, full immunization. Multiple factors have contributed to current concerns, including the interdependent issues of an evolving communications environment and shortfalls in structure and resources that constrain research on immunization safety (immunization-safety science). Prompt attention by public health leadership to spreading concern about the safety of immunization is essential for protecting deserved public trust in immunization.

Changes in health in England with analysis by English region and areas of deprivation: findings of the Global Burden of Disease Study 2013

Summary Background In the Global Burden of Disease Study 2013 (GBD 2013), knowledge about health and its determinants has been integrated into a comparable framework to inform health policy. Outputs of this analysis are relevant to current policy questions in England and elsewhere, particularly on health inequalities. We use GBD 2013 data on mortality and causes of death, and disease and injury incidence and prevalence to analyse the burden of disease and injury in England as a whole, in English regions, and within each English region by deprivation quintile. We also assess disease and injury burden in England attributable to potentially preventable risk factors. England and the English regions are compared with the remaining constituent countries of the UK and with comparable countries in the European Union (EU) and beyond. Methods We extracted data from the GBD 2013 to compare mortality, causes of death, years of life lost (YLLs), years lived with a disability (YLDs), and disability-adjusted life-years (DALYs) in England, the UK, and 18 other countries (the first 15 EU members [apart from the UK] and Australia, Canada, Norway, and the USA [EU15+]). We extended elements of the analysis to English regions, and subregional areas defined by deprivation quintile (deprivation areas). We used data split by the nine English regions (corresponding to the European boundaries of the Nomenclature for Territorial Statistics level 1 [NUTS 1] regions), and by quintile groups within each English region according to deprivation, thereby making 45 regional deprivation areas. Deprivation quintiles were defined by area of residence ranked at national level by Index of Multiple Deprivation score, 2010. Burden due to various risk factors is described for England using new GBD methodology to estimate independent and overlapping attributable risk for five tiers of behavioural, metabolic, and environmental risk factors. We present results for 306 causes and 2337 sequelae, and 79 risks or risk clusters. Findings Between 1990 and 2013, life expectancy from birth in England increased by 5·4 years (95% uncertainty interval 5·0–5·8) from 75·9 years (75·9–76·0) to 81·3 years (80·9–81·7); gains were greater for men than for women. Rates of age-standardised YLLs reduced by 41·1% (38·3–43·6), whereas DALYs were reduced by 23·8% (20·9–27·1), and YLDs by 1·4% (0·1–2·8). For these measures, England ranked better than the UK and the EU15+ means. Between 1990 and 2013, the range in life expectancy among 45 regional deprivation areas remained 8·2 years for men and decreased from 7·2 years in 1990 to 6·9 years in 2013 for women. In 2013, the leading cause of YLLs was ischaemic heart disease, and the leading cause of DALYs was low back and neck pain. Known risk factors accounted for 39·6% (37·7–41·7) of DALYs; leading behavioural risk factors were suboptimal diet (10·8% [9·1–12·7]) and tobacco (10·7% [9·4–12·0]). Interpretation Health in England is improving although substantial opportunities exist for further reductions in the burden of preventable disease. The gap in mortality rates between men and women has reduced, but marked health inequalities between the least deprived and most deprived areas remain. Declines in mortality have not been matched by similar declines in morbidity, resulting in people living longer with diseases. Health policies must therefore address the causes of ill health as well as those of premature mortality. Systematic action locally and nationally is needed to reduce risk exposures, support healthy behaviours, alleviate the severity of chronic disabling disorders, and mitigate the effects of socioeconomic deprivation. Funding Bill & Melinda Gates Foundation and Public Health England.

Strategies for addressing vaccine hesitancy – A systematic review☆

UNLABELLED The purpose of this systematic review is to identify, describe and assess the potential effectiveness of strategies to respond to issues of vaccine hesitancy that have been implemented and evaluated across diverse global contexts. METHODS A systematic review of peer reviewed (January 2007-October 2013) and grey literature (up to October 2013) was conducted using a broad search strategy, built to capture multiple dimensions of public trust, confidence and hesitancy concerning vaccines. This search strategy was applied and adapted across several databases and organizational websites. Descriptive analyses were undertaken for 166 (peer reviewed) and 15 (grey literature) evaluation studies. In addition, the quality of evidence relating to a series of PICO (population, intervention, comparison/control, outcomes) questions defined by the SAGE Working Group on Vaccine Hesitancy (WG) was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria; data were analyzed using Review Manager. RESULTS Across the literature, few strategies to address vaccine hesitancy were found to have been evaluated for impact on either vaccination uptake and/or changes in knowledge, awareness or attitude (only 14% of peer reviewed and 25% of grey literature). The majority of evaluation studies were based in the Americas and primarily focused on influenza, human papillomavirus (HPV) and childhood vaccines. In low- and middle-income regions, the focus was on diphtheria, tetanus and pertussis, and polio. Across all regions, most interventions were multi-component and the majority of strategies focused on raising knowledge and awareness. Thirteen relevant studies were used for the GRADE assessment that indicated evidence of moderate quality for the use of social mobilization, mass media, communication tool-based training for health-care workers, non-financial incentives and reminder/recall-based interventions. Overall, our results showed that multicomponent and dialogue-based interventions were most effective. However, given the complexity of vaccine hesitancy and the limited evidence available on how it can be addressed, identified strategies should be carefully tailored according to the target population, their reasons for hesitancy, and the specific context.

Measuring vaccine confidence: analysis of data obtained by a media surveillance system used to analyse public concerns about vaccines

BACKGROUND The intensity, spread, and effects of public opinion about vaccines are growing as new modes of communication speed up information sharing, contributing to vaccine hesitancy, refusals, and disease outbreaks. We aimed to develop a new application of existing surveillance systems to detect and characterise early signs of vaccine issues. We also aimed to develop a typology of concerns and a way to assess the priority of each concern. METHODS Following preliminary research by The Vaccine Confidence Project, media reports (eg, online articles, blogs, government reports) were obtained using the HealthMap automated data collection system, adapted to monitor online reports about vaccines, vaccination programmes, and vaccine-preventable diseases. Any reports that did not meet the inclusion criteria--any reference to a human vaccine or vaccination campaign or programme that was accessible online--were removed from analysis. Reports were manually analysed for content and categorised by concerns, vaccine, disease, location, and source of report, and overall positive or negative sentiment towards vaccines. They were then given a priority level depending on the seriousness of the reported event and time of event occurrence. We used descriptive statistics to analyse the data collected during a period of 1 year, after refinements to the search terms and processes had been made. FINDINGS We analysed data from 10,380 reports (from 144 countries) obtained between May 1, 2011, and April 30, 2012. 7171 (69%) contained positive or neutral content and 3209 (31%) contained negative content. Of the negative reports, 1977 (24%) were associated with impacts on vaccine programmes and disease outbreaks; 1726 (21%) with beliefs, awareness, and perceptions; 1371 (16%) with vaccine safety; and 1336 (16%) with vaccine delivery programmes. We were able to disaggregate the data by country and vaccine type, and monitor evolution of events over time and location in specific regions where vaccine concerns were high. INTERPRETATION Real-time monitoring and analysis of vaccine concerns over time and location could help immunisation programmes to tailor more effective and timely strategies to address specific public concerns. FUNDING Bill & Melinda Gates Foundation.

The State of Vaccine Confidence 2016: Global Insights Through a 67-Country Survey

Background Public trust in immunization is an increasingly important global health issue. Losses in confidence in vaccines and immunization programmes can lead to vaccine reluctance and refusal, risking disease outbreaks and challenging immunization goals in high- and low-income settings. National and international immunization stakeholders have called for better monitoring of vaccine confidence to identify emerging concerns before they evolve into vaccine confidence crises. Methods We perform a large-scale, data-driven study on worldwide attitudes to immunizations. This survey – which we believe represents the largest survey on confidence in immunization to date – examines perceptions of vaccine importance, safety, effectiveness, and religious compatibility among 65,819 individuals across 67 countries. Hierarchical models are employed to probe relationships between individual- and country-level socio-economic factors and vaccine attitudes obtained through the four-question, Likert-scale survey. Findings Overall sentiment towards vaccinations is positive across all 67 countries, however there is wide variability between countries and across world regions. Vaccine-safety related sentiment is particularly negative in the European region, which has seven of the ten least confident countries, with 41% of respondents in France and 36% of respondents in Bosnia & Herzegovina reporting that they disagree that vaccines are safe (compared to a global average of 13%). The oldest age group (65+) and Roman Catholics (amongst all faiths surveyed) are associated with positive views on vaccine sentiment, while the Western Pacific region reported the highest level of religious incompatibility with vaccines. Countries with high levels of schooling and good access to health services are associated with lower rates of positive sentiment, pointing to an emerging inverse relationship between vaccine sentiments and socio-economic status. Conclusions Regular monitoring of vaccine attitudes – coupled with monitoring of local immunization rates – at the national and sub-national levels can identify populations with declining confidence and acceptance. These populations should be prioritized to further investigate the drivers of negative sentiment and to inform appropriate interventions to prevent adverse public health outcomes.

Public Health Response to Influenza A(H1N1) as an Opportunity to Build Public Trust

IN JUNE 2009, THE WORLD HEALTH ORGANIZATION (WHO) declared the 2009 influenza A(H1N1) pandemic and in October 2009, President Obama declared it a national emergency. The influenza A(H1N1) virus is being monitored around the world for changes in virulence or epidemiology. There has been a push to have vaccines ready, yet vaccine supply may be insufficient in some areas. The public wants to be assured that there is enough vaccine, but at the same time, some are questioning the safety and effectiveness of the vaccine. It is a time of uncertainty both for the public health community and for the public. Times of uncertainty and risk are times when public trust is most needed. But trust is built long before the time that trust matters most. As the public weighs the perceived risks of the A(H1N1) virus against the perceived risks of vaccination, they are taking into account multiple, often conflicting, sources of current and historic information, as well as their own personal experiences. Questioning the safety of A(H1N1) vaccines is for some influenced by memories of the 1976 US swine flu alert, of the follow-up swine flu vaccination campaign and the ensuing cases of GuillainBarre syndrome (GBS), and of a swine flu pandemic that never materialized. For others, questioning may come from memories of severe acute respiratory syndrome (SARS), which had severe but rapidly contained health effects; for others, questions may arise from warnings about avian influenza A(H5N1) and its continued pandemic threat. Perception of risk about A(H1N1) vaccination is also influenced by a broader environment of distrust and vocal antivaccine groups. Questioning and mistrust of the measles-mumpsrubella (MMR) vaccine in the United Kingdom that began during the late 1990s was prompted by the claimed association between the MMR vaccine, bowel disease, and autism. This claim came shortly after a loss of public trust around the government’s lack of transparency and understating of the risks of bovine spongiform encephalopathy. Even after clear evidence emerged that these claims about autism being related to vaccines were unfounded, historic levels of distrust, compounded by massive media coverage that amplified the unproven links between the MMR vaccine and bowel disease, played a role in contributing to lower vaccine coverage and consequent disease outbreaks. In France, public trust in hepatitis B vaccine plummeted after the government’s precautionary decision to stop the school vaccination program because of suspected, but not proven, links with multiple sclerosis, despite recommendations by WHO and French pediatricians to continue the program. This followed concerns over the French government’s management of the human immunodeficiency virus (HIV)–contaminated blood crisis in the mid-1980s, and public opposition and rumors associating hepatitis B vaccines with not only multiple sclerosis but also autism and leukemia led to low levels of hepatitis B vaccination. In Nigeria, the mistrust and 2003-2004 boycott of the polio vaccination program by predominantly Muslim states in Northern Nigeria emerged at a time when false rumors of the safety of polio vaccine—linked to HIV, hormonal contamination, or both—weakened trust in global initiatives such as polio eradication. This followed a 1996 drug trial of an antibiotic for meningitis in Nigeria in which children died. Adding to the mistrust, repeated door-to-door polio vaccination campaigns are thought to have increased levels of suspicion in historically marginalized states. In these states, health services are inadequate, immunization coverage is lower than in the rest of the country, and communities questioned why other diseases, perceived by them to be more important, continued to be neglected. The loss of public confidence and vaccination boycott led to a resurgence of polio cases in Nigeria. The Nigerian virus spread to more than 12 neighboring countries that had been certified as poliofree and polio caused by the Nigerian strain was traced as far as Indonesia. Significant efforts have since been made at the community level in Northern Nigeria to build public

The India HPV-vaccine suspension

572 www.thelancet.com Vol 376 August 21, 2010 In response to demands from advocacy groups, the Indian Government has suspended demonstration projects for HPV vaccination in Andhra Pradesh and Gujarat. The episode provides salutary lessons about how a lack of public confi dence can amplify if not quickly addressed. The fi rst lesson is timing. Too often, the response to citizen advocates who question health interventions, programmes, or studies, is too late. The April, 2010, memorandum from 68 Indian human rights and women’s groups, academics, and individuals sent to the Indian Minister of Health and Family Welfare should not have been a surprise. A similar memo had been sent 6 months earlier. The April memo called for the immediate halt of the demonstration projects until “concerns relating to safety, effi cacy and cost eff ectiveness of the planned interventions are re-evaluated”. It also demanded an inquiry into, and compensation for, the reported side-eff ects and alleged vaccine-related deaths of four girls who participated in the study. The deaths have since been investigated and confi rmed as unrelated to the vaccine. Similarly, the memorandum sent on Oct 1, 2009, demanded that “all trials and studies be immediately brought to a halt till in an open forum questions relating to safety, effi cacy and cost eff ectiveness of the planned intervention can be justifi ed”. On Dec 28, 2009, the groups continued their unanswered pleas and convened a public meeting that generated more attention than the October memorandum. By February, GlaxoSmithKline, Merck, and PATH had issued responses on the safety of the vaccine and on the process of the study. The India HPV-vaccine suspension resulted in extremely conformal treatment capabilities. Proton radiotherapy provides the most conformal approach with the lowest likelihood of radiation penetrating unintended regions of the body, and has been used for paediatric cancers, particularly CNS tumours, in centres with a proton facility. Children suff er the most severe long-term sequelae from radiation and are the most likely to live decades if cured. Therefore proton facilities should make treating children with cancer a high priority, including young women requiring abdominal or pelvic radiation that might scatter to aff ect the uterus or ovary. For premenopausal women, potential options for preservation of fertility should be discussed. Should uterine irradiation be unavoidable, parents should be informed that their daughter’s off spring might be at risk of stillbirth and neonatal death when their daughter reaches adulthood. For childhood cancer survivors, reproductive counselling and testing in a specialised centre to assess the feasibility and potential risks associated with a pregnancy should be discussed, and a plan implemented to ensure a successful outcome.