David Salisbury

Planning, registration, and implementation of an immunisation campaign against meningococcal serogroup C disease in the UK: a success story

The introduction of meningococcal C conjugate (MCC) vaccine in the UK in November 1999 as a routine 3 dose infant immunisation course, with a single catch-up dose for all children aged between 12 months and 17 years, was the result of an intensive 5 year collaborative research programme funded by the Department of Health for England and involving public bodies, academia and vaccine manufacturers. The research programme established the safety and immunogenicity of MCC vaccines in infants, toddlers, pre-school and school-aged children. The nature and frequency of common adverse events in school-aged children was similar to that after a booster dose of diphtheria and tetanus vaccine given to the same age groups. The recommendation that a single dose was adequate for children aged 12 months and above was based on antibody levels measured by serum bactericidal assay and evidence of induction of immunological memory as shown by maturation of antibody avidity. Licensure by the Medicines Control Agency was based on serological criteria alone without direct evidence of efficacy and has set a precedent for other meningococcal conjugate polysaccharide vaccines. Vaccine coverage of around 85% was achieved in the targeted age groups and has resulted in a drop in the incidence of serogroup C disease in these groups of over 80% within 18 months of the start of the vaccination programme. Early post-licensure efficacy estimates for toddlers and teenagers (88 and 96%, respectively, in the first 16 months after vaccination) validate the serological criteria used for licensure. Surveillance of the prevalent serogroups and serosubtypes among invasive case isolates has shown no evidence of any capsular switching to serogroup B during the first 18 months of the MCC vaccination programme.

Development of vaccines against meningococcal disease

Neisseria meningitidis is a major cause of bacterial meningitis and sepsis. Polysaccharide-protein conjugate vaccines for prevention of group C disease have been licensed in Europe. Such vaccines for prevention of disease caused by groups A (which is associated with the greatest disease burden worldwide), Y, and W135 are being developed. However, conventional approaches to develop a vaccine for group B strains, which are responsible for most cases in Europe and the USA, have been largely unsuccessful. Capsular polysaccharide-based vaccines can elicit autoantibodies to host polysialic acid, whereas the ability of most non-capsular antigens to elicit broad-based immunity is limited by their antigenic diversity. Many new membrane proteins have been discovered during analyses of genomic sequencing data. These antigens are highly conserved and, in mice, elicit serum bactericidal antibodies, which are the serological hallmark of protective immunity in man. Therefore, there are many promising new vaccine candidates, and improved prospects for development of a broadly protective vaccine for group B disease, and for control of all meningococcal disease.

Compulsory vaccination and conscientious or philosophical exemptions: Past, present, and future

Compulsory vaccination has contributed to the success of immunisation programmes in the USA and Australia, yet the benefits from compulsory vaccination are not universally recognised. Some people--experts and the public alike--believe that the benefits of compulsory vaccination are outweighed by the associated ethical problems. A review of vaccination legislation in the UK, Australia, and the USA raises four main points. First, compulsory vaccination may be effective in preventing disease outbreaks, reaching and sustaining high immunisation coverage rates, and expediting the introduction of new vaccines. Second, to be effective, compulsory programmes must have a reliable supply of safe and effective vaccines and most people must be willing to be vaccinated. Third, allowance of exemptions to compulsory vaccination may limit public backlash. Finally, compulsory vaccination may increase the burden on governments to ensure the safety of vaccines. Nevertheless, although compulsory immunisation can be very effective, it might not be acceptable in some countries where high coverage has been achieved through other approaches or efforts, such as in Sweden, Norway, Denmark, the Netherlands, and the UK. These factors should be considered when compulsory vaccinations are being introduced or immunisation laws refined. Lessons learned from compulsory vaccination could be useful to other public-health programmes.

Meningococcal C conjugate vaccine: The experience in England and Wales

Meningococcal C conjugate vaccine was introduced in the UK in November 1999 together with a comprehensive meningococcal surveillance strategy to support and inform the vaccine programme. These surveillance data have provided important information on the long-term effectiveness of the programme, through direct and indirect protection, and on the prevalent serotypes and serosubtypes causing invasive meningococcal infection subsequent to vaccine introduction. The MCC immunization programme has been extremely successful in controlling serogroup C disease and continues to be evaluated. The aim of this paper is to review the experiences in England and Wales over the past 9 years.

Recommendations from the national vaccine advisory committee: Standards for adult immunization practice

National Vaccine Advisory Committee The Advisory Committee on Immunization Practices (ACIP) makes recommendations for routine vaccination of adults in the United States.1 Standards for implementing the ACIP recommendations for adults were published by the National Vaccine Advisory Committee (NVAC) in 20032 and by the Infectious Diseases Society of America in 2009.3 In addition, NVAC published a report in 2012 outlining a pathway for improving adult immunization rates.4 While most of these documents included guidelines for immunization practice, recent changes in the practice climate for adult immunization necessitated an update of existing adult immunization standards. Some of these changes include expansion of vaccination services offered by pharmacists and other community immunization providers both during and since the 2009 H1N1 influenza pandemic; vaccination at the workplace; increased vaccination by providers who care for pregnant women; and changes in the health-care system, including the Affordable Care Act (ACA), which requires first-dollar coverage of ACIP-recommended vaccines for people with certain private insurance plans, or those who are beneficiaries of expanded Medicaid plans.5 The ACA first-dollar provision is expected to increase the number of adults who will be insured for vaccines. Other changes include expanding the inclusion of adults in state immunization information systems (IISs) (i.e., registries) and the Centers for Medicare & Medicaid Services Meaningful Use Stage 2 requirements, which mandate provider reporting of immunizations to registries, including reporting of adult vaccination in states where such reporting is allowed.6 For the purposes of this report, provider refers to any individual who provides health-care services to adult patients, including physicians, physician assistants, nurse practitioners, nurses, pharmacists, and other health-care professionals. While previous versions of the adult immunization standards have been published, recommendations for adult vaccination are published annually, and many health-care organizations have endorsed routine assessment and vaccination of adults, vaccination among adults continues to be low.7–15 Several barriers to adult vaccination include:

A Global Perspective on Vaccine Safety and Public Health: The Global Advisory Committee on Vaccine Safety

Established in 1999, the Global Advisory Committee on Vaccine Safety advises the World Health Organization (WHO) on vaccine-related safety issues and enables WHO to respond promptly, efficiently, and with scientific rigor to issues of vaccine safety with potential global importance. The committee also assesses the implications of vaccine safety for practice worldwide and for WHO policies. We describe the principles on which the committee was established, its modus operandi, and the scope of the work undertaken, both present and future. We highlight its recent recommendations on major issues, including the purported link between the measles-mumps-rubella vaccine and autism and the safety of the mumps, influenza, yellow fever, BCG, and smallpox vaccines as well as that of thiomersal-containing vaccines.

Measles vaccination and Guillain-Barré syndrome

BACKGROUND Guillain-Barré syndrome (GBS) has been associated with several infectious agents, and the possibility that the disorder may be caused by vaccination has been raised. We compared the numbers of cases of GBS observed immediately after mass measles vaccination campaigns with the numbers that would be expected from baseline rates, to assess whether there is a causal relation between measles vaccination and GBS. METHODS We analysed data on 2296 cases of GBS reported to the Poliomyelitis Eradication Surveillance System of the Pan American Health Organization as cases of suspected poliomyelitis. These cases occurred among 73 million immunised children aged 9 months to 15 years in Argentina, Brazil, Chile, and Colombia, between January, 1990, and December, 1994. These children were targeted for mass measles vaccination campaigns (each lasting 1 month) in 1992 and 1993. The frequency of GBS cases observed during the vaccination campaigns or the next 42 days (the latent period) was compared with that during the rest of the study period, with the assumption of a Poisson distribution. FINDINGS The average annual incidence of GBS was 0.62 per 100000 children aged 1-14 years. The number of cases that would be expected within any 72-day period would therefore be 92. The average observed number of cases during latent periods after measles vaccination was 97. The probability that 97 or more cases would occur during a period with an expected number of 92 was 0.31. INTERPRETATION The average annual rates of GBS by age-group for the 5 years analysed were consistent with previous data; thus we are confident that the surveillance system is sufficiently sensitive. There was no statistically significant association between measles vaccination and GBS. If there is any causal relation, the number of GBS cases due to measles vaccination was so small that data from the vaccination of more than 70 million children were not sufficient to detect a rise in the number of observed GBS cases beyond the expected number.

Parental response to the introduction of a vaccine against human papilloma virus.

The introduction of a vaccine against human papillomavirus (HPV), a sexually transmitted virus that is the causal factor of at least 95% of invasive cervical cancer, could significantly reduce the number of cases of cervical cancer occurring in the UK each year. To ensure that individuals are protected before onset of sexual activity, it is likely that the vaccine will be offered to children around 10 years of age. It is important that parents’ attitudes to HPV vaccination are taken into account, particularly as the subject relates to sexual health issues. In order to gauge parents’ initial responses to the addition of HPV vaccine to the immunisation programme and identify the issues needing further research, in-depth interviews were held with parents of girls and boys aged 8-10 years. Our results show that most parents have not heard of HPV and were not aware of the role of HPV in cervical cancer. There were concerns about offering a vaccine that protects against a sexually transmitted infection to children and that the vaccine should be offered at an older age in conjunction with a sex education programme. In order to avoid rejection of this vaccine, work needs to take place now to raise awareness of HPV as a cause of cervical cancer prior to any introduction of the vaccination programme.

Establishing global policy recommendations: the role of the Strategic Advisory Group of Experts on immunization

The vaccine landscape has changed considerably over the last decade with many new vaccines and technological developments, unprecedented progress in reaching out to children and the development of new financing mechanisms. At the same time, there are more demands and additional expectations of national policy makers, donors and other interested parties for increased protection through immunization. The Global Immunization Vision and Strategy (GIVS), which broadens the previous scope of immunization efforts, sets a number of goals to be met by countries. The WHO has recently reviewed and adjusted both its policy making structure and processes for vaccines and immunization to include an enlarged consultation process to generate evidence-based recommendations, thereby ensuring the transparency of the decision making process and improving communications. This article describes the process of development of immunization policy recommendations at the global level and some of their impacts. It focuses on the roles and modes of operating of the Strategic Advisory Group of Experts on immunization, which is the overarching advisory group involved with the issuance of policy recommendations, monitoring and facilitating the achievement of the GIVS goals. The article also describes the process leading to the publication of WHO vaccine position papers, which provide WHO recommendations on vaccine use. WHO vaccine-related recommendations have become a necessary step in the pathway to the introduction and use of vaccines, especially in developing countries and, consequently, have a clear and significant impact.

Translating vaccine policy into action: a report from the Bill & Melinda Gates Foundation Consultation on the prevention of maternal and early infant influenza in resource-limited settings.

Immunization of pregnant women against influenza is a promising strategy to protect the mother, fetus, and young infant from influenza-related diseases. The burden of influenza during pregnancy, the vaccine immunogenicity during this period, and the robust influenza vaccine safety database underpin recommendations that all pregnant women receive the vaccine to decrease complications of influenza disease during their pregnancies. Recent data also support maternal immunization for the additional purpose of preventing disease in the infant during the first six months of life. In April 2012, the WHO Strategic Advisory Group of Experts (SAGE) on Immunization recommended revisions to the WHO position paper on influenza vaccines. For the first time, SAGE recommended pregnant women should be made the highest priority for inactivated seasonal influenza vaccination. However, the variable maternal influenza vaccination coverage in countries with pre-existing maternal influenza vaccine recommendations underscores the need to understand and to address the discrepancy between recommendations and implementation success. We present the outcome of a multi-stakeholder expert consultation on inactivated influenza vaccination in pregnancy. The creation and implementation of vaccine policies and regulations require substantial resources and capacity. As with all public health interventions, the existence of perceived and real risks of vaccination will necessitate effective and transparent risk communication. Potential risk allocation and sharing mechanisms should be addressed by governments, vaccine manufacturers, and other stakeholders. In resource-limited settings, vaccine-related issues concerning supply, formulation, regulation, evidence evaluation, distribution, cost-utility, and post-marketing safety surveillance need to be addressed. Lessons can be learned from the Maternal and Neonatal Tetanus Elimination Initiative as well as efforts to increase vaccine coverage among pregnant women during the 2009 influenza pandemic. We conclude with an analysis of data gaps and necessary activities to facilitate implementation of maternal influenza immunization programs in resource-limited settings.