Elimination of cervical cancer: Lessons learned from polio and earlier eradication programs.

This paper reviews definitions of control, elimination, and eradication and considers lessons learned from prior and current elimination/eradication efforts that might inform the current effort to eliminate cervical cancer. This task is complicated by the varying definitions of elimination extant. Lessons for cervical cancer elimination notably include the necessity for political will/champions; the need for a specific target with a time span; the need for program efforts to be guided by surveillance of disease and death (not just coverage); the need for accountability, monitoring, and evaluation at all levels; and the need for ongoing research. Although achieving the goal of elimination will be difficult, success will mean the prevention of millions of deaths due to cervical cancer.

An opportunity to incentivize innovation to increase vaccine safety in the United States by improving vaccine delivery using vaccine patches.

Vaccines represent cost-effective and safe interventions that provide substantial health and economic benefits to individuals and populations. The US vaccine enterprise that supports all aspects of immunization continues to encourage innovation. Despite some limited historical recommendations to create a fund to support investments in vaccine safety, and recent legislation that supports innovation for new vaccines (the 21st Century Cures Act, Public Law 114-255), to date the US lacks financial incentives to fund innovation in vaccine delivery technologies. Building on separate reviews of the US Vaccine Injury Compensation Program (VICP) and the state of development of vaccine patches as an innovative vaccine delivery platform, we suggest an opportunity to allocate some VICP Trust Fund resources to prevent future VICP claims by creating a new incentives fund to support translational studies for improving vaccine delivery technologies. We identify shoulder injury related to vaccine administration (SIRVA) as a test case.

Adherence to Timely Vaccinations in the United States.

OBJECTIVES: To estimate (1) the proportion of children not adhering to the Advisory Committee on Immunization Practices (ACIP) recommended early childhood immunization schedule and (2) associations between schedule adherence, sociodemographic characteristics, and up-to-date immunization status by 19 to 35 months of age. METHODS: We used 2014 National Immunization Survey provider-verified vaccination data to classify vaccination patterns as "recommended" (ie, in line with ACIP dose- and age-specific recommendations), "alternate" (ie, in line with either limiting the number of shots per visit or skipping at least 1 vaccine series), or "unknown or unclassifiable" (ie, not in line with ACIP recommendations or clearly limiting shots per visit or vaccine series). We evaluated the association between vaccination patterns and up-to-date status for all ACIP-recommended vaccinations (including rotavirus and hepatitis A vaccines) using Poisson regression. RESULTS: The majority of children's patterns were classified as "recommended" (63%), with 23% and 14% following alternate or unknown or unclassifiable patterns, respectively; 58% of children were up-to-date with all ACIP-recommended immunizations by 19 to 35 months. Not being up-to-date was associated with alternate (prevalence ratio = 4.2, 95% confidence interval: 3.9-4.5) and unknown or unclassifiable (prevalence ratio = 2.4, 95% confidence interval: 2.2-2.7) patterns. CONCLUSIONS: High vaccine coverage by 19 to 35 months of age may miss nonadherence to the recommended immunization schedule in the first 18 months of life, leaving children vulnerable to preventable diseases. With more than one-third of US children not following the ACIP schedule, targeted interventions are needed to minimize vaccine delays and disease susceptibility.

Performance of the United States Vaccine Injury Compensation Program (VICP): 1988-2019.

The United States (US) highly values the individual and societal benefits of vaccination and invests significantly in vaccine development and use as part of its national vaccine enterprise. In 1986, recognizing the small, but non-zero risks associated with vaccines, the US created a mechanism to collect excise taxes on each dose of vaccine to fund a national Vaccine Injury Compensation Program (VICP). The VICP includes a system for those claiming serious injuries from vaccines to seek compensation, and a process to pay individuals with legitimate claims and their legal counsel. Given the maturity of the VICP, we review experience with the vaccines and injuries covered, claims, and economics of the fund. Our review shows the excellent safety track record of vaccines, provides some evidence of injuries related specifically to vaccine delivery, and discusses the financial health of the fund.

The Global Vaccine Action Plan - insights into its utility, application, and ways to strengthen future plans.

BACKGROUND: The pace of global progress must increase if the Global Vaccine Action Plan (GVAP) goals are to be achieved by 2020. We administered a two-phase survey to key immunization stakeholders to assess the utility and application of GVAP, including how it has impacted country immunization programs, and to find ways to strengthen the next 10-year plan. METHODS: For the Phase I survey, an online questionnaire was sent to global immunization stakeholders in summer 2017. The Phase II survey was sent to regional and national immunization stakeholders in summer 2018, including WHO Regional Advisors on Immunization, Expanded Programme on Immunization managers, and WHO and UNICEF country representatives from 20 countries. Countries were selected based on improvements (10) versus decreases (10) in DTP3 coverage from 2010 to 2016. RESULTS: Global immunization stakeholders (n = 38) cite global progress in improving vaccine delivery (88%) and engaging civil society organizations as advocates for vaccines (83%). Among regional and national immunization stakeholders (n = 58), 70% indicated reaching mobile and underserved populations with vaccination activities as a major challenge. The top ranked activities for helping country programs achieve progress toward GVAP goals include improved monitoring of vaccination coverage and upgrading disease surveillance systems. Most respondents (96%) indicated GVAP as useful for determining immunization priorities and 95% were supportive of a post-2020 GVAP strategy. CONCLUSIONS: Immunization stakeholders see GVAP as a useful tool, and there is cause for excitement as the global immunization community looks toward the next decade of vaccines. The next 10-year plan should attempt to increase political will, align immunization activities with other health system agendas, and address important issues like reaching mobile/migrant populations and improving data reporting systems.

The partnership for influenza vaccine introduction (PIVI): Supporting influenza vaccine program development in low and middle-income countries through public-private partnerships.

Influenza vaccination remains the most effective tool for reducing seasonal influenza disease burden. Few Low and Middle-Income Countries (LMICs) have robust, sustainable annual influenza national vaccination programs. The Partnership for Influenza Vaccine Introduction (PIVI) was developed as a public-private partnership to support LMICs to develop and sustain national vaccination programs through time-limited vaccine donations and technical support. We review the first 5 years of experience with PIVI, including the concept, country progress toward sustainability, and lesson learned. Between 2013 and 2018, PIVI worked with Ministries of Health in 17 countries. Eight countries have received donated vaccines and technical support; of these, two have transitioned to sustained national support of influenza vaccination and six are increasing national support of the vaccine programs towards full transition to local vaccine program support by 2023. Nine additional countries have received technical support for building the evidence base for national policy development and/or program evaluation. PIVI has resulted in increased use of vaccines in partner countries, and early countries have demonstrated progress towards sustainability, suggesting that a model of vaccine and technical support can work in LMICs. PIVI expects to add new country partners as current countries transition to self-reliance.

What Is Needed to Eliminate Hepatitis B Virus and Hepatitis C Virus as Global Health Threats.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) cause 1.3 million deaths annually. To prevent more than 7 million deaths by 2030, the World Health Organization set goals to eliminate HBV and HCV, defined as a 90% reduction in new infections and a 65% reduction in deaths, and prevent more than 7 million related deaths by 2030. Elimination of HBV and HCV is feasible because of characteristics of the viruses, reliable diagnostic tools, and available cost-effective or cost-saving interventions. Broad implementation of infant immunization against HBV, blood safety, and infection-control programs have greatly reduced the burden of HBV and HCV infections. To achieve elimination, priorities include implementation of HBV vaccine-based strategies to prevent perinatal transmission, safe injection practices and HCV treatment for persons who inject drugs, and testing and treatment for HBV- and HCV-infected persons. With sufficient capacity, HBV and HCV elimination programs can meet their goals.

Development of a US trust measure to assess and monitor parental confidence in the vaccine system.

OBJECTIVE: To develop a Vaccine Confidence Index (VCI) that is capable of detecting variations in parental confidence towards childhood immunizations centered on trust and concern issues that impact vaccine confidence. METHODS: We used a web-based national poll of 893 parents of children <7 years in 2016 to assess the measures created for the Emory VCI (EVCI). EVCI measures were developed using constructs related to vaccine confidence identified by the U.S. National Vaccine Advisory Committee (i.e., "Information Environment", "Trust", "Healthcare Provider", "Attitudes and Beliefs", and "Social Norms"). Reliability for EVCI was assessed using Cronbach's alpha. Using the variables related to each of the constructs, we calculated an overall EVCI score that was then assessed against self-reported childhood vaccine receipt using chi-square and the Cochrane-Armitage trend tests. RESULTS: Respondents' EVCI scores could range from 0 to 24, and the full range of values was observed in this sample (Mean = 17.5 (SD 4.8)). EVCI scores were significantly different (p ≤ 0.006 for all comparisons) between parents who indicated their child(ren) received routinely recommended vaccines compared with parents who indicated they had delayed or declined recommended immunizations. There was also a significant, consistent association between higher EVCI scores and greater reported vaccine receipt. CONCLUSIONS: We developed EVCI to reliably measure parental vaccine confidence, with individuals' scores linked to parental vaccine-related attitudes, intentions, and behaviors. As such, EVCI may be a useful tool for future monitoring of both population and individual confidence in childhood immunization.

The National Vaccine Advisory Committee at 30: Impact and opportunity.

Thirty years after passage of legislation that created the National Vaccine Advisory Committee (NVAC) "to achieve optimal prevention of human infectious diseases through immunization and to achieve optimal prevention against adverse reactions to vaccines," this review reflects NVAC's role and impact on the U.S. vaccine and immunization enterprise as an external advisor to the Department of Health and Human Services. We reviewed the history of NVAC in the context of the principles of its establishment, with a focus on its reports and recommendations. We performed a systematic literature review to identify NVAC reports published in widely-accessible public health journals, and we reviewed the available archives to identify other reports and resolutions approved by the committee not published in journals. We characterized key issues considered by NVAC according to the five goals of the 2010 National Vaccine Plan. The predominance of NVAC activities to date related to the implementation of immunization across the lifespan and the many aspects of the system needed to foster the goal of full immunization. Reflecting on the impacts of NVAC to date, this review identified 30 NVAC approved reports published in journals, 22 stand-alone resolutions, and 26 unique unpublished reports. The development of new and improved vaccines continues to represent a significant priority for NVAC, and we identified several challenges related to future vaccine innovation. Given the many factors that impact on policy changes in the vaccine and immunization enterprise, we encountered challenges associated with demonstrating attribution of specific policy changes to NVAC recommendations. Although difficult to quantify, this review suggests that NVAC played an important role in the improvements in the U.S. immunization enterprise over the past 30 years and that NVAC can and will continue to play an important role supporting U.S. immunization going forward.

Measles and rubella eradication.

This article discusses concepts of eradication, some issues relating to vertical and horizontal public health programs, some current issues relating to measles and rubella, and what we need to do about them. It concludes that measles and rubella/CRS can and should be eradicated. A target date should be established in 2020 (or before). Eradication can only be accomplished in the context of strengthening ongoing immunization services and strengthening surveillance so it can guide activities. Additional resources will be required to achieve the goal.

Monitoring Results in Routine Immunization: Development of Routine Immunization Dashboard in Selected African Countries in the Context of the Polio Eradication Endgame Strategic Plan.

Background: To monitor immunization-system strengthening in the Polio Eradication Endgame Strategic Plan 2013-2018 (PEESP), the Global Polio Eradication Initiative identified 1 indicator: 10% annual improvement in third dose of diphtheria- tetanus-pertussis-containing vaccine (DTP3) coverage in polio high-risk districts of 10 polio focus countries. Methods: A multiagency team, including staff from the African Region, developed a comprehensive list of outcome and process indicators measuring various aspects of the performance of an immunization system. Results: The development and implementation of the dashboard to assess immunization system performance allowed national program managers to monitor the key immunization indicators and stratify by high-risk and non-high-risk districts. Discussion: Although only a single outcome indicator goal (at least 10% annual increase in DTP3 coverage achieved in 80% of high-risk districts) initially existed in the endgame strategy, we successfully added additional outcome indicators (eg, decreasing the number of DTP3-unvaccinated children) as well as program process indicators focusing on cold chain, stock availability, and vaccination sessions to better describe progress on the pathway to raising immunization coverage. Conclusion: When measuring progress toward improving immunization systems, it is helpful to use a comprehensive approach that allows for measuring multiple dimensions of the system.

Transition Planning For After Polio Eradication.

The Global Polio Eradication Initiative (GPEI) has been in operation since 1988, now spends $1 billion annually, and operates through thousands of staff and millions of volunteers in dozens of countries. It has brought polio to the brink of eradication. After eradication is achieved, what should happen to the substantial assets, capabilities, and lessons of the GPEI? To answer this question, an extensive process of transition planning is underway. There is an absolute need to maintain and mainstream some of the functions, to keep the world polio-free. There is also considerable risk-and, if seized, substantial opportunity-for other health programs and priorities. And critical lessons have been learned that can be used to address other health priorities. Planning has started in the 16 countries where GPEI's footprint is the greatest and in the program's 5 core agencies. Even though poliovirus transmission has not yet been stopped globally, this planning process is gaining momentum, and some plans are taking early shape. This is a complex area of work-with difficult technical, financial, and political elements. There is no significant precedent. There is forward motion and a willingness on many sides to understand and address the risks and to explore the opportunities. Very substantial investments have been made, over 30 years, to eradicate a human pathogen from the world for the second time ever. Transition planning represents a serious intent to responsibly bring the world's largest global health effort to a close and to protect and build upon the investment in this effort, where appropriate, to benefit other national and global priorities. Further detailed technical work is now needed, supported by broad and engaged debate, for this undertaking to achieve its full potential.

Protective Effect of Contemporary Pertussis Vaccines: A Systematic Review and Meta-analysis.

BACKGROUND: Acellular pertussis (aP) and whole-cell (wP) pertussis vaccines are presumed to have similar short-term (<3 years after completion of the primary series) efficacy. However, vaccine effect varies between individual pertussis vaccine formulations, and many originally studied formulations are now unavailable. An updated analysis of the short-term protective effect of pertussis vaccines limited to formulations currently on the market in developed countries is needed. METHODS: We conducted a systematic review and meta-analysis of published studies that evaluated pertussis vaccine efficacy or effectiveness within 3 years after completion (>3 doses) of a primary series of a currently available aP or wP vaccine formulation. The primary outcome was based on the World Health Organization (WHO) clinical case definitions for pertussis. Study quality was assessed using the approach developed by the Child Health Epidemiology Research Group. We determined overall effect sizes using random-effects meta-analyses, stratified by vaccine (aP or wP) and study (efficacy or effectiveness) type. RESULTS: Meta-analysis of 2 aP vaccine efficacy studies (assessing the 3-component GlaxoSmithKline and 5-component Sanofi-Pasteur formulations) yielded an overall aP vaccine efficacy of 84% (95% confidence interval [CI], 81%-87%). Meta-analysis of 3 wP vaccine effectiveness studies (assessing the Behringwerke, Pasteur/Mérieux, and SmithKline Beecham formulations) yielded an overall wP vaccine effectiveness of 94% (95% CI, 88%-97%) (bothI(2)= 0%). CONCLUSIONS: Although all contemporary aP and wP formulations protect against pertussis disease, in this meta-analysis the point estimate for short-term protective effect against WHO-defined pertussis in young children was lower for currently available aP vaccines than wP vaccines.

Immunization equity.

Health inequities are the unjust differences in health among different social groups. Unfortunately, inequities are the norm, both in terms of health status and access to, and use of, health services. Childhood immunizations reduce the incidence of vaccine-preventable diseases and represent a cost-effective way to foster health equity. This paper reflects a 2015 review of data from surveys conducted in developing countries from 2005 to 2011 that show significant inequities in immunization coverage and discusses several initiatives currently underway (including Gavi, the Vaccine Alliance) that are directed at increasing childhood immunizations or reducing or abolishing overall health inequities. These initiatives have already had a significant impact on disease burden and childhood mortality and give rise to optimism that health disparities may further be reduced and health equity achieved as a result of investments made in immunization.

Immunization Equity.

Health inequities are the unjust differences in health among different social groups. Unfortunately, inequities are the norm, both in terms of health status and access to, and use of, health services. Childhood immunizations reduce the incidence of vaccine-preventable diseases and represent a cost-effective way to foster health equity. This paper reflects a 2015 review of data from surveys conducted in developing countries from 2005 to 2011 that show significant inequities in immunization coverage and discusses several initiatives currently underway (including Gavi, the Vaccine Alliance) that are directed at increasing childhood immunizations or reducing or abolishing overall health inequities. These initiatives have already had a significant impact on disease burden and childhood mortality and give rise to optimism that health disparities may further be reduced and health equity achieved as a result of investments made in immunization.

Challenges and changes: immunization program managers share perspectives in a 2012 national survey about the US immunization system since the H1N1 pandemic response.

In mid-2012 we conducted survey of immunization program managers (IPMs) for the purpose of describing relationships between immunization programs and emergency preparedness programs, IPM's perceptions of challenges encountered and changes made or planned in programmatic budgeting, vaccine allocation and pandemic plans as a result of the H1N1 vaccination campaign. Over 95% of IPMs responded (61/64) to the survey. IPMs reported that a primary budget-related challenge faced during H1N1 included staff-related restrictions that limited the ability to hire extra help or pay regular staff overtime resulting in overworked regular staff. Other budget-related challenges related to operational budget shortfalls and vaccine procurement delays. IPMs described overcoming these challenges by increasing staff where possible, using executive order or other high-level support by officials to access emergency funds and make policy changes, as well as expedite hiring and spending processes according to their pandemic influenza plan or by direction from leadership. Changes planned for response to future pandemic vaccine allocation strategies were to "tailor the strategy to the event" taking into account disease virulence, vaccine production rates and public demand, having flexible vaccine allocation strategies, clarifying priority groups for vaccine receipt to providers and the public, and having targeted clinics such as through pharmacies or schools. Changes already made to pandemic plans were improving strategies for internal and external communication, improving vaccine allocation efficiency, and planning for specific scenarios. To prepare for future pandemics, programs should ensure well-defined roles, collaborating during non-emergency situations, sustaining continuity in preparedness funding, and improved technologies.