Improving access to affordable vaccines for middle-income countries in the african region

Despite the remarkable power of immunization reducing morbidity and mortality due to vaccine preventable diseases, one in five African children still does not receive all the basic, necessary vaccines. This is particularly true of the 10 middle-income countries (MICs) in the WHO African Region, where data demonstrates that immunization coverage is decreasing. These countries are not eligible for Gavi support in accessing new vaccines because of their relatively high per capita income level and will gradually increase with the transitioning of countries out of Gavi support. Thus, WHO was requested to facilitate access to affordable vaccines in relation to middle-income countries and those transitioning out of Gavi support in the near future. With commitment to address the issue, WHO Regional Office for Africa convened a consultative meeting from 09 to 11 April 2018 in Brazzaville, Congo to explore ways of improving access to affordable vaccines for MICs in the Region. The meeting brought together 17 low, middle and upper middle income countries in the African Region. Immunization partners and other WHO Regions also participated in the consultation to share experiences and explore ways of increasing access to affordable vaccines in MICs in the African Region. At the end of the meeting a number of solutions and action points were proposed for implementation in the Region.     

Conditionality of COVID-19 vaccine acceptance in European countries

The COVID-19 vaccine rollout has offered a powerful preventive measure to help control SARS-CoV-2 transmission. Nevertheless, long-standing public hesitation around vaccines heightened concerns that vaccine coverage would not achieve desired public health impacts, particularly in light of more contagious variants. This cross-sectional survey was conducted online just before the European vaccine rollout in December 2020 among 7000 respondents (aged 18–65) in Belgium, France, Germany, Italy, Spain, Sweden, and Ukraine. The survey included open text boxes for fuller explanation of responses. Overall, 56.9% of respondents would accept a COVID-19 vaccine, 19.0% would not, and 24.1% did not know or preferred not to say. By country, between 44% (France) and 66% (Italy) of respondents would accept a COVID-19 vaccine. Respondents expressed conditionality in open responses, voicing concerns about vaccine safety and mistrust of authorities. We highlight lessons learned about the dynamism of vaccine conditionality and persistence of safety concerns.     

中国人用疫苗上市情况分析与展望

本文分析了中国2019年批签发的人用疫苗种类、数量、生产企业等,对比了国内外疫苗行业发展趋势,展望了中国疫苗发展前景。中国免疫规划疫苗发展平稳,非免疫规划疫苗有较大发展空间,多联多价疫苗、治疗性疫苗和应急疫苗发展迅速。中国需鼓励疫苗产业研发与生产,进一步提高疫苗上市后的安全、有效和合理可及性。     

Challenges for the registration of vaccines in emerging countries: Differences in dossier requirements,application and evaluation processes

The divergence of regulatory requirements and processes in developing and emerging countries contributes to hamper vaccines’ registration, and therefore delay access to high-quality, safe and efficacious vaccines for their respective populations. This report focuses on providing insights on the heterogeneity of registration requirements in terms of numbering structure and overall content of dossiers for marketing authorisation applications for vaccines in different areas of the world. While it also illustrates the divergence of regulatory processes in general, as well as the need to avoid redundant reviews, it does not claim to provide a comprehensive view of all processes nor existing facilitating mechanisms, nor is it intended to touch upon the differences in assessments made by different regulatory authorities. This report describes the work analysed by regulatory experts from vaccine manufacturing companies during a meeting held in Geneva in May 2017, in identifying and quantifying differences in the requirements for vaccine registration in three aspects for comparison: the dossier numbering structure and contents, the application forms, and the evaluation procedures, in different countries and regions. The Module 1 of the Common Technical Document (CTD) of 10 countries were compared. Modules 2–5 of the CTDs of two regions and three countries were compared to the CTD of the US FDA. The application forms of eight countries were compared and the registration procedures of 134 importing countries were compared as well. The analysis indicates a high degree of divergence in numbering structure and content requirements. Possible interventions that would lead to significant improvements in registration efficiency include alignment in CTD numbering structure, a standardised model-application form, and better convergence of evaluation procedures.     

A cost analysis of producing vaccines in developing countries

Developing country vaccine manufacturers (DCVMs) supply over half of the vaccines used in developing country immunisation programs. Decisions by developing countries to establish vaccine manufacturing should be based on economic viability, however reliable assessments of vaccine production costs are lacking. This study aimed to quantify the cost of establishing vaccine manufacturing facilities and producing vaccines in developing countries.This study estimates vaccine production costs in developing countries based on twelve vaccines produced by eight DCVMs. The results were based on estimates of the capital and operating costs required to establish vaccine manufacturing facilities under three hypothetical scenarios of production scale and scope. Cost patterns were then compared to vaccine prices paid by countries in both industrialized and developing country markets.The cost of producing vaccines in developing countries was estimated to be on average US$ 2.18 per dose, ranging between US$ 0.98 and US$ 4.85 for different vaccine types and formulations. Vaccine costs-per-dose decrease as production scale and scope increase. Cost-per-dose is mainly driven by fixed costs, but at a scale of production over 20 million doses per year it becomes driven by variable costs. Under the three hypothetical scenarios used, costs-per-dose of vaccines produced by developing countries were around 47% lower than vaccine prices in developing-country markets and 84% lower than prices in industrialized-country markets.This study has found that local production of vaccines in developing countries exhibits both economies of scale and economies of scope. The lower costs relative to prices suggests that a producer surplus and potential profits may be attainable in both developing and developed country markets, supporting sustainable production.     

The role of emerging manufacturers in access to innovative vaccines of public health importance

The role of developing country manufacturers in assuring global access to innovative vaccines was compared to the situation in 2005. These producers now supply over 60% of traditional vaccines doses globally and an increasing value (up to 15% in 2007) of innovative products. More suppliers are now strong players in global market, and an even larger group has potential to do so. These manufacturers are not a homogeneous group and most of them are now at a crossroads. Decisions made by their management and governments as well as by the international community will have a large impact on their existence and future and their ability to manufacture innovative vaccines at affordable prices.     

Vaccination in newly arrived immigrants to the European Union

The challenge of assimilating millions of immigrants in the European region each year presents significant socioeconomic issues. Among them is the threat of vaccine preventable diseases (VPDs) disease transmission within immigrant groups and the broader population given the permeability of nation state borders. A total of 3.8 million people immigrated to the European Union (EU) in 2014, among those were 1.6 million non-EU nationals. While vaccines have markedly reduced the transmission of disease, clusters of under-vaccinated individuals potentiate the rapid transmission of once-eradicated or controlled diseases. Immigrants pose a special challenge to host country public health vaccination programmes. Wars in their native countries may have interrupted vaccination programmes, documentation may be unavailable or unreliable, and refugees may present with health issues due to poor sanitation and food during transit. Further, immigrants are often reticent to access health care in the destination country, or may face financial or language barriers. Thus, preventive health care needs may go unaddressed and the first contact with a clinician is for an emergency. Equitable access to acute and preventive health care and services, including immunizations irrespective of individual’s immigration status, should be a priority for European region countries. Ensuring appropriate and timely vaccination for immigrants could be accomplished with a universal European region immunization schedule. Priority should be given to highly communicable VPDs such as measles, mumps, rubella, pertussis, diphtheria, varicella and polio.     

Infant mortality and diminished entelechy in three European countries

Individual-level research reports that adverse environmental conditions during infancy increase the risk of mortality later in life. Extending this model to populations implies what we call the “diminished entelechy” hypothesis in which birth cohorts subjected to virulent environmental insults early in life experience increased mortality at older ages and do not realize their otherwise expected lifespan. Controversy remains as to whether the individual-level findings generalize to populations. We test the “diminished entelechy” hypothesis by measuring the association between infant mortality and life expectancy at age one for males and females born in Sweden (1751–1912), Denmark (1835–1913), and England and Wales (1841–1912). Time-series methods control for trends and other forms of autocorrelation that could confound the associations. Results support diminished entelechy in Sweden and England and Wales, but not in Denmark, in that environmental insults during infancy appear associated with reduced cohort lifespan. We then explored when in the life course the sequelae of infancy appear most salient. We examined cohort associations between infant mortality and mortality during childhood (1–4 years), youth (5–19 years), adulthood (20–54 years), and old-age (55–79 years). We generally find that infant cohort effects appear to “program” the mortality experience in youth, but not in adulthood or old-age. These findings conflict with the notion that improved conditions during infancy shaped the historical decline of old-age mortality.     

Government,politics and health policy: A quantitative analysis of 30 European countries

RationalePublic health policies are often dependent on political decision-making, but little is known of the impact of different forms of government on countries’ health policies. In this exploratory study we studied the association between a wide range of process and outcome indicators of health policy and four groups of political factors (levels of democracy, e.g. voice and accountability; political representation, e.g. voter turnout; distribution of power, e.g. constraints on the executive; and quality of government, e.g. absence of corruption) in contemporary Europe.Data and methodsData on 15 aspects of government and 18 indicators of health policy as well as on potential confounders were extracted from harmonized international data sources, covering 30 European countries and the years 1990–2010. In a first step, multivariate regression analysis was used to relate cumulative measures of government to indicators of health policy, and in a second step panel regression with country fixed effects was used to relate changes in selected measures of government to changes in indicators of health policy.ResultsIn multivariate regression analyses, measures of quality of democracy and quality of government had many positive associations with process and outcome indicators of health policy, while measures of distribution of power and political representation had few and inconsistent associations. Associations for quality of democracy were robust against more extensive control for confounding variables, including tests in panel regressions with country fixed effects, but associations for quality of government were not.ConclusionsIn this period in Europe, the predominant political influence on health policy has been the rise of levels of democracy in countries in the Central & Eastern part of the region. In contrast to other areas of public policy, health policy does not appear to be strongly influenced by institutional features of democracy determining the distribution of power, nor by aspects of political representation. The effect of quality of government on health policy warrants more study.     

Has the public lost confidence in vaccines because of a vaccine scandal in China

BackgroundA vaccine manufacturer in China and regulatory authorities have been the focus of widespread outrage due to a vaccine scandal. We conducted a rapid survey during a time of intense mainstream and social media attention to determine whether the public’s confidence in vaccines was affected.MethodsWe selected 7 cities that were not involved in the scandal as the setting for the survey, which was conducted in August 2018. We used a convenience sampling strategy to select subjects in urban streets and rural villages for a face-to-face questionnaire-based survey. Subjects were asked to describe their levels of confidence on a scale from 0 to 9, in which 0 means no confidence, and 9 means very confident. Respondents were asked to assess confidence for two points in time – recollection of their level of confidence before hearing about the scandal and their level of confidence at the time of the survey.ResultsIn total, 683 individuals were invited to participate and 591 questionnaires were completed, for a response rate of 86.5%. Among respondents, 86.80% had heard of the vaccine scandal. The most common channel for hearing about the scandal was social media (e.g., WeChat), 40.6% of respondents. Regardless of gender, age, education level, province, town or country, or having children under 15 years old, respondents reported a significant decrease in confidence in domestically-produced vaccines. The mean pre-scandal confidence level recalled by respondents was 6.7, and the mean confidence level at the time of the survey was 3.2. Confidence in vaccine manufacturers, institutes for drug control, and drug supervision authorities decreased from 5.6 to 6.0 before the vaccine scandal to 2.0–3.2 at the time of the survey. Confidence in vaccine manufacturers decreased the most, from 5.6 before the scandal to 2.0; confidence in institutes for drug control decreased from 5.8 before the scandal to 2.6 at the time of the survey.ConclusionThis study demonstrated that public confidence was significantly affected by the vaccine scandal, particularly for vaccine producers and drug regulators. The decline in confidence is a reminder to governments that in order to build public confidence for vaccination, regulators have to reform regulatory practices and manufacturers have to ensure vaccine quality.     

Vaccinomics,the new road to tick vaccines

Ticks are a threat to human and animal health worldwide. Ticks are considered to be second worldwide to mosquitoes as vectors of human diseases, the most important vectors of diseases that affect cattle industry worldwide and important vectors of diseases affecting pets. Tick vaccines are a cost-effective and environmentally friendly alternative to protect against tick-borne diseases through the control of vector infestations and reducing pathogen infection and transmission. These premises stress the need for developing improved tick vaccines in a more efficient way. In this context, development of improved vaccines for tick-borne diseases will be greatly enhanced by vaccinomics approaches starting from the study of tick–host–pathogen molecular interactions and ending in the characterization and validation of vaccine formulations. The discovery of new candidate vaccine antigens for the control of tick infestations and pathogen infection and transmission requires the development of effective screening platforms and algorithms that allow the analysis and validation of data produced by systems biology approaches to tick research. Tick vaccines that affect both tick infestations and pathogen transmission could be used to vaccinate human and animal populations at risk and reservoir species to reduce host exposure to ticks while reducing the number of infected ticks and their vectorial capacity for pathogens that affect human and animal health worldwide.     

A comparison of the alcohol-attributable mortality in four European countries

Background: Deaths due to alcohol consumption are an important component of all-cause mortality, particularly premature mortality. However, there are considerable regional variations, the reasons for which are unclear. Methods: Estimates were made as reliably as possibly using vital statistics and best estimates of risk of the alcohol-attributable mortality, by age, sex and cause for four European countries (England and Wales, Germany, Denmark and Italy). Twenty-seven alcohol-related conditions were considered including the possible cardio-protective effects of alcohol. Results: It was estimated that there are approximately 2% fewer deaths annually in England and Wales than would be expected in a non-drinking population and 0.3% fewer deaths among East German females. In West Germany, Denmark, Italy and among East German males there are more deaths caused by alcohol than are prevented (between 0.7 and 2.6% of all deaths). The highest age-specific proportion of alcohol-attributable deaths is found in East Germany where around 30% of deaths among males aged 25–44 years are due to drinking. Among young men in all four countries the largest contributor to alcohol-related deaths is road traffic accidents involving alcohol. Conclusions: Possible explanations for the variation in alcohol-attributable deaths between countries include different underlying heart disease rates, different patterns of alcohol consumption and beverage preferences, and different use of mortality classification. Differences in the reported alcohol consumption levels explain little of the variation in alcohol-attributable deaths. Estimating alcohol-attributable mortality by age and sex across countries may be a useful indicator for developing alcohol strategies and exploring ways of preventing premature mortality.     

National immunization strategies targeting migrants in six European countries

Over the last three years an unprecedented flow of migrants arrived in Europe. There is evidence that vaccine preventable diseases have caused outbreaks in migrant holding centres. These outbreaks can be favored by a combination of factors including low immunization coverage, bad conditions that migrants face during their exhausting journey and overcrowding within holding facilities. In 2017, we conducted an online survey in Croatia, Greece, Italy, Malta, Portugal and Slovenia to explore the national immunization strategies targeting irregular migrants, refugees and asylum seekers. All countries stated that a national regulation supporting vaccination offer to migrants is available. Croatia, Italy, Portugal and Slovenia offer to migrant children and adolescents all vaccinations included in the National Immunization Plan; Greece and Malta offer only certain vaccinations, including those against diphtheria-tetanus-pertussis, poliomyelitis and measles-mumps-rubella. Croatia, Italy, Malta and Portugal also extend the vaccination offer to adults. All countries deliver vaccinations in holding centres and/or community health services, no one delivers vaccinations at entry site. Operating procedures that guarantee the migrants’ access to vaccination at the community level are available only in Portugal. Data on administered vaccines is available at the national level in four countries: individual data in Malta and Croatia, aggregated data in Greece and Portugal. Data on vaccination uptake among migrants is available at national level only in Malta. Concluding, although diversified, strategies for migrant vaccination are in place in all the surveyed countries and generally in line with WHO and ECDC indications. Development of procedures to keep track of migrants’ immunization data across countries, development of strategies to facilitate and monitor migrants’ access to vaccinations at the community level and collection of data on vaccination uptake among migrants should be promoted to meet existing gaps.     

Health care reform in six Central European countries

This study gives an overview of the health care reform in six Central European countries after the transition from a central planning system to a regulated market economy. We focused on cost containment policies for drugs, especially the requirements for submitting health economic data in the pricing and/or reimbursement processes. The literature review was supplemented with a survey with decision makers at national health authorities in each country. The study covered Croatia, Czech Republic, Hungary, Poland, Slovakia, and Slovenia. All countries had in common that health economic information was used in reimbursement rather than in pricing processes. Differences between the six countries were mainly variations in the relative importance of health economic data and the presence of explicit requirements and guidelines. Published health economic guidelines exist in two countries and one of the six countries applies a mandatory submission system for a selected range of new drugs. In most of the Central European countries it is more typical that authorities issue a brief list of required data for reimbursement submissions that include health economic information among other data. There is a generally widespread expectation towards more systematic and formalized requirements for health economic and outcomes research data appearing within the next 3–5 years in the region.     

Policies for immunization against rubella in European countries

In 1986 a survey on immunization policies against rubella was conducted in 17 European countries. A questionnaire was sent to each Ministry of Health and selected practitioners, requesting information on official policy for vaccination against rubella, level of policy decision, immunization strategy, target groups, current recommendations for vaccination, measures taken to facilitate vaccine uptake, vaccine strains used and legislation concerning abortion.A policy for the prevention of congenital rubella is explicitly defined in 16 countries (in 12 at a national level, in 3 at a regional level and in one at both levels). In Greece only, no official policy has been defined, although the practice is to vaccinate infants over 15 months of age and girls by 9–11 years of age. There are 3 countries maintaining the selective strategy of vaccinating teenage girls, but in 8 countries this strategy changed to a mass vaccination of young infants. In 5 other countries an approach combining both mass immunization and selective vaccination is adopted. This situation of different strategies between countries in Europe could have a deleterious effect for young migrants or travelling pregnant women and could reduce the effectiveness of programmes for prevention of congenital rubella syndrome. Harmonization of immunization policies and of recommendations for vaccine administration is advisable. The mass vaccination of all young children combined with systematic revaccination either of all children or of teenage girls is probably the most effective approach for elimination of congenital rubella syndrome in Europe.Corresponding author.     

The prevalence of known diabetes in eight European countries

BACKGROUND: The prevalence of diabetes has been proposed as a European Community Health Indicator. The prevalence of diabetes known to general practitioners (GPs) in different European countries has been investigated and the usefulness of sentinel practice networks in delivering prevalence data on diabetes has been evaluated. METHODS: Patients presenting with diabetes in a 12 month period (1999/2000) to GPs in established European sentinel practice surveillance networks in eight European countries were registered. Estimates of prevalence were standardized to the 1998 European population. RESULTS: All-age prevalence reported in the network populations was lowest in Slovenia (male 16, female 16 per 1000) and highest in Belgium (male 31, female 34). The range of estimates obtained in this study was narrower than that published by the WHO in the Health For All database. The range was further reduced by age standardization. In males aged 45 years and over, age standardized prevalence ranged from 39 (Slovenia) to 76 (Belgium) and in females from 37 (Slovenia) to 75 (Belgium). There were no consistent gender differences in national prevalence rates. CONCLUSIONS: The study demonstrates the capacity of sentinel practice networks to deliver data on the prevalence of known diabetes in persons over 45 years. National differences in prevalence are less than hitherto reported. Prevalence in Belgium measured in all ages and in 45 years and over males and females was higher than in the seven other countries.     

The complementary roles of Phase 3 trials and post-licensure surveillance in the evaluation of new vaccines

Vaccines have led to significant reductions in morbidity and saved countless lives from many infectious diseases and are one of the most important public health successes of the modern era. Both vaccines’ effectiveness and safety are keys for the success of immunisation programmes. The role of post-licensure surveillance has become increasingly recognised by regulatory authorities in the overall vaccine development process. Safety, purity, and effectiveness of vaccines are carefully assessed before licensure, but some safety and effectiveness aspects need continuing monitoring after licensure; Post-marketing activities are a necessary complement to pre-licensure activities for monitoring vaccine quality and to inform public health programmes. In the recent past, the availability of large databases together with data-mining and cross-linkage techniques have significantly improved the potentialities of post-licensure surveillance. The scope of this review is to present challenges and opportunities offered by vaccine post-licensure surveillance. While pre-licensure activities form the foundation for the development of effective and safe vaccines, post-licensure monitoring and assessment, are necessary to assure that vaccines are effective and safe when translated in real world settings. Strong partnerships and collaboration at an international level between different stakeholders is necessary for finding and optimally allocating resources and establishing robust post-licensure processes.     

Influenza vaccination uptake and socioeconomic determinants in 11 European countries

Background

The objective of this study was to assess the predictive effects of socioeconomic factors to explain influenza vaccination coverage rates in 11 European countries.

Methods

Data from national household surveys collected over up to seven consecutive seasons between 2001/2002 and 2007/2008 were analyzed to assess the associations of socioeconomic factors with immunization against influenza.

Results

In total, data from 92,101 household contacts representative for the national non-institutionalized population aged above 14 years were analyzed. Influenza vaccination coverage rates in Europe remain suboptimal with little or no progress in the last years. The results of this study indicate that gender, household income, size of household, educational level and population size of living residence may significantly contribute to explain chances of getting immunized against influenza apart from the known risk factors age and chronic illness. The effect of these socioeconomic factors was differently expressed among the countries and could not be explained solely on basis of economic characteristics of these countries.

Conclusions

Future measures should address inequalities to achieve the WHO target by 2010 with an influenza vaccination rate of 75% in the elderly. National vaccination campaigns may need to take socioeconomic segments of the population here identified as less likely of getting the influenza vaccine into account.