David Smith

Understanding vaccine hesitancy around vaccines and vaccination from a global perspective: A systematic review of published literature, 2007–2012

Vaccine hesitancy is an emerging term in the literature and discourse on vaccine decision-making and determinants of vaccine acceptance. It recognizes a continuum between the domains of vaccine acceptance and vaccine refusal and de-polarizes previous characterization of individuals and groups as either anti-vaccine or pro-vaccine. The primary aims of this systematic review are to: 1) identify research on vaccine hesitancy; 2) identify determinants of vaccine hesitancy in different settings including its context-specific causes, its expression and its impact; and 3) inform the development of a model for assessing determinants of vaccine hesitancy in different settings as proposed by the Strategic Advisory Group of Experts Working Group (SAGE WG) for dealing with vaccine hesitancy. A broad search strategy, built to capture multiple dimensions of public trust, confidence and hesitancy around vaccines, was applied across multiple databases. Peer-reviewed studies were selected for inclusion if they focused on childhood vaccines [≤ 7 years of age], used multivariate analyses, and were published between January 2007 and November 2012. Our results show a variety of factors as being associated with vaccine hesitancy but they do not allow for a complete classification and confirmation of their independent and relative strength of influence. Determinants of vaccine hesitancy are complex and context-specific - varying across time, place and vaccines.

Preliminary report The effect of low-glycemic carbohydrate on insulin and glucose response in vivo and in vitro in patients with coronary heart disease☆

The insulin resistance syndrome has recently been implicated in the etiology of coronary heart disease, with a possible metabolic defect at the level of the adipocyte. We report the effects of a low- versus high-glycemic-index (LGI and HGI, respectively) diet on insulin and glucose response as assessed by oral glucose tolerance test (OGTT) and insulin-stimulated glucose uptake in isolated adipocytes in a group of 32 patients with advanced coronary heart disease. The area under the insulin curve following OGTT was significantly reduced after 4 weeks in the LGI group (P < .03), but not in the HGI group. Insulin-stimulated glucose uptake in isolated adipocytes harvested from a presternal fat biopsy was significantly greater following the LGI diet (P < .05). This study demonstrates that simple short-term dietary measures can improve insulin sensitivity in patients with coronary heart disease.

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

BACKGROUNDnThe 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.nnnMETHODSnFollowing 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.nnnFINDINGSnWe 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.nnnINTERPRETATIONnReal-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.nnnFUNDINGnBill & Melinda Gates Foundation.

Recombinant pseudorabies virus carrying a Plasmodium gene: herpesvirus as a new live viral vector for inducing T- and B-cell immunity

In Balb/c mice, the sterile protective immunity induced by immunization with radiation-attenuated Plasmodium yoelii sporozoites is eliminated by in vivo depletion of CD8+ T lymphocytes, suggesting that cytotoxic T lymphocytes (CTL) against malaria antigens expressed on infected hepatocytes are required for mediating this protective immunity. To produce a vaccine that would induce CTL against the P. yoelii circumsporozoite protein (CS), we constructed an attenuated pseudorabies virus (PRV) containing a gene encoding this protein. Balb/c mice that received three doses of 10(7) plaque-forming units (p.f.u.) of this vaccine intravenously at 3 week intervals developed high levels of antibodies to sporozoites (indirect fluorescent antibody titre = 4096) and CTL against a 16 amino acid epitope (SYVPSAEQILEFVKQI, amino acids 281-296) from the P. yoelii CS protein designated PYCTL1. The cytotoxic activity of the CTL was antigen-specific, MHC-restricted, and dependent on CD8+ T cells. Furthermore, these CTL eliminated P. yoelii-infected hepatocytes from in vitro culture, indicating that they recognize this peptide on the surface of infected hepatocytes. However, all nine mice that were challenged with 200 sporozoites developed a blood-stage malaria infection. We attribute this lack of protection to the great difficulty of inducing sterile immunity against this highly infectious parasite P. yoelii. We conclude that recombinant pseudorabies virus (PRV) worked successfully as a live vaccine vector to induce both antibodies and CTL, albeit non-protective in vivo, and the herpesviruses should be considered as subunit vaccines where T- and B-cell immunity is required.

Measuring Vaccine Confidence: Introducing a Global Vaccine Confidence Index

Background. Public confidence in vaccination is vital to the success of immunisation programmes worldwide. Understanding the dynamics of vaccine confidence is therefore of great importance for global public health. Few published studies permit global comparisons of vaccination sentiments and behaviours against a common metric. This article presents the findings of a multi-country survey of confidence in vaccines and immunisation programmes in Georgia, India, Nigeria, Pakistan, and the United Kingdom (UK) – these being the first results of a larger project to map vaccine confidence globally. Methods. Data were collected from a sample of the general population and from those with children under 5 years old against a core set of confidence questions. All surveys were conducted in the relevant local-language in Georgia, India, Nigeria, Pakistan, and the UK. We examine confidence in immunisation programmes as compared to confidence in other government health services, the relationships between confidence in the system and levels of vaccine hesitancy, reasons for vaccine hesitancy, ultimate vaccination decisions, and their variation based on country contexts and demographic factors. Results. The numbers of respondents by country were: Georgia (n=1000); India (n=1259); Pakistan (n=2609); UK (n=2055); Nigerian households (n=12554); and Nigerian health providers (n=1272). The UK respondents with children under five years of age were more likely to hesitate to vaccinate, compared to other countries. Confidence in immunisation programmes was more closely associated with confidence in the broader health system in the UK (Spearman’s ρ=0.5990), compared to Nigeria (ρ=0.5477), Pakistan (ρ=0.4491), and India (ρ=0.4240), all of which ranked confidence in immunisation programmes higher than confidence in the broader health system. Georgia had the highest rate of vaccine refusals (6 %) among those who reported initial hesitation. In all other countries surveyed most respondents who reported hesitating to vaccinate went on to receive the vaccine except in Kano state, Nigeria, where the percentage of those who ultimately refused vaccination after initially hesitating was as high as 76%) Reported reasons for hesitancy in all countries were classified under the domains of “confidence,” “convenience,” or “complacency,” and confidence issues were found to be the primary driver of hesitancy in all countries surveyed.

Human Survival at Older Ages and the Implications for Longevity Bond Pricing

Abstract Governments are concerned about the future of pension plans, for which increasing longevity is judged to be an important risk to their future viability. We focus on human survival at age 65, the starting age point for many pension products. Using a simple model, we link basic measures of life expectancy to the shape of the human survival function and consider its various forms. The model is then used as the basis for investigating actual survival in England and Wales. We find that life expectancy is increasing at a faster rate than at any time in history, with no evidence of this trend slowing or any upper age limit. With interest growing in the use of longevity bonds as a way to transfer longevity risks from pension providers to the capital markets, we seek to understand how longevity drift affects pension liabilities based on mortality rates at the point of annuitization, versus what actually happens as a cohort ages. The main findings are that longevity bonds are an effective hedge against longevity risk; however, it is not only the oldest old that are driving risk, but also more 65-year-olds reaching less extreme ages such as 80. In addition, we find that the possibility of future inflation and interest rates could be as an important a risk to annuities as longevity itself.

Social justice and the (South African) city : retrospect and prospect

ABSTRACT Thirty years since publication of David Harveys Social Justice and the City is an appropriate time for a review of social justice and the South African city. The issue is complicated by questions of definition what qualifies as ‘the city’ or ‘urban’ in this context. Alternative theoretical perspectives have proliferated over the past thirty years, but they share common concerns with the distribution of means of well-being and the structures involved. The social injustice of apartheid was easy to demonstrate, from various theoretical perspectives. While the end of apartheid promised a more just society, gross inequalities are being perpetuated in the post-apartheid city and in society at large. The present trajectory is indefensible morally; in this respect, South Africa may be a microcosm of the world at large. Social justice in the (South African) city requires fundamental changes in political economy and its moral foundations, not only in this country but globally.

Forecasted trends in vaccination coverage and correlations with socioeconomic factors: a global time-series analysis over 30 years

BACKGROUNDnIncomplete immunisation coverage causes preventable illness and death in both developing and developed countries. Identification of factors that might modulate coverage could inform effective immunisation programmes and policies. We constructed a performance indicator that could quantitatively approximate measures of the susceptibility of immunisation programmes to coverage losses, with an aim to identify correlations between trends in vaccine coverage and socioeconomic factors.nnnMETHODSnWe undertook a data-driven time-series analysis to examine trends in coverage of diphtheria, tetanus, and pertussis (DTP) vaccination across 190 countries over the past 30 years. We grouped countries into six world regions according to WHO classifications. We used Gaussian process regression to forecast future coverage rates and provide a vaccine performance index: a summary measure of the strength of immunisation coverage in a country.nnnFINDINGSnOverall vaccine coverage increased in all six world regions between 1980 and 2010, with variation in volatility and trends. Our vaccine performance index identified that 53 countries had more than a 50% chance of missing the Global Vaccine Action Plan (GVAP) target of 90% worldwide coverage with three doses of DTP (DTP3) by 2015. These countries were mostly in sub-Saharan Africa and south Asia, but Austria and Ukraine also featured. Factors associated with DTP3 immunisation coverage varied by world region: personal income (Spearmans ρ=0·66, p=0·0011) and government health spending (0·66, p<0·0001) were informative of immunisation coverage in the Eastern Mediterranean between 1980 and 2010, whereas primary school completion was informative of coverage in Africa (0·56, p<0·0001) over the same period. The proportion of births attended by skilled health staff correlated significantly with immunisation coverage across many world regions.nnnINTERPRETATIONnOur vaccine performance index highlighted countries at risk of failing to achieve the GVAP target of 90% coverage by 2015, and could aid policy makers assessments of the strength and resilience of immunisation programmes. Weakening correlations with socioeconomic factors show a need to tackle vaccine confidence, whereas strengthening correlations point to clear factors to address.nnnFUNDINGnUK Engineering and Physical Sciences Research Council.

A new method of projecting populations based on trends in life expectancy and survival

There is increasing concern about the lack of accuracy in population projections at national levels. A common problem has been the systematic underestimation of improvements in mortality, especially at older ages, resulting in projections that are too low. In this paper, we present a method that is based on projecting survivorship rather than mortality, which uses the same data but differs technically. In particular, rather than extrapolating trends in mortality, we use trends in life expectancy to establish a robust statistical relation between changes in life expectancy and survivorship using period life tables. We test the approach on data for England and Wales for the population aged 50 and over, and show that it gives more accurate projections than official projections using the same base data. Using the model to project the population aged 50 and over to 2020, our method suggests nearly 0.6 million more people in this age group than official projections.

A functional connectome: regulation of Wnt/TCF-dependent transcription by pairs of pathway activators

BackgroundWnt/β-catenin signaling is often portrayed as a simple pathway that is initiated by Wnt ligand at the cell surface leading, via linear series of interactions between ‘core pathway’ members, to the induction of nuclear transcription from genes flanked by β-catenin/TCF transcription factor binding sites. Wnt/β-catenin signaling is also regulated by a much larger set of ‘non-core regulators’. However the relationship between ‘non-core regulators’ is currently not well understood. Aberrant activation of the pathway has been shown to drive tumorgenesis in a number of different tissues.MethodsMammalian cells engineered to have a partially-active level of Wnt/β-catenin signaling were screened by transfection for proteins that up or down-regulated a mid-level of TCF-dependent transcription induced by transient expression of an activated LRP6 Wnt co-receptor (∆NLRP).Results141 novel regulators of TCF-dependent transcription were identified. Surprisingly, when tested without ∆NLRP activation, most up-regulators failed to alter TCF-dependent transcription. However, when expressed in pairs, 27 % (466/1170) functionally interacted to alter levels of TCF-dependent transcription. When proteins were displayed as nodes connected by their ability to co-operate in the regulation of TCF-dependent transcription, a network of functional interactions was revealed. In this network, ‘core pathway’ components (Eg. β-catenin, GSK-3, Dsh) were found to be the most highly connected nodes. Activation of different nodes in this network impacted on the sensitivity to Wnt pathway small molecule antagonists.ConclusionsThe ‘functional connectome’ identified here strongly supports an alternative model of the Wnt pathway as a complex context-dependent network. The network further suggests that mutational activation of highly connected Wnt signaling nodes predisposed cells to further context-dependent alterations in levels of TCF-dependent transcription that may be important during tumor progression and treatment.