Documenting the Full Value of Vaccination: A Systematic Review of Value Frameworks.

OBJECTIVES: Economic evaluations of vaccination may not fully account for nonhealth patient impacts on families, communities, and society (ie, broader value elements). Omission of broader value elements may reflect a lack of established measurement methodology, lack of agreement over which value elements to include in economic evaluations, and a lack of consensus on whether the value elements included should vary by vaccination type or condition. We conducted a systematic review of value frameworks to identify broader value elements and measurement guidance that may be useful for capturing the full value of vaccination. METHODS: We searched Ovid MEDLINE, PubMed, Embase, and the gray literature to identify value frameworks for all health interventions, and we extracted information on each framework's context, value elements, and any available guidance on how these elements should be measured. We used descriptive statistics to analyze and compare the prevalence of broader value elements in vaccination value frameworks and other healthcare-related value frameworks. RESULTS: Our search identified 62 value frameworks that met inclusion criteria, 9 of which were vaccination specific. Although vaccination frameworks included several broader value elements, such as reduced transmissibility and public health benefits, the elements were represented inconsistently across the frameworks. Vaccination frameworks omitted several value elements included in nonvaccination-specific frameworks, including dosing and administration complexity and affordability. In addition, guidance for measuring broader value elements was underdeveloped. CONCLUSIONS: Future efforts should further evaluate inclusion of broader value elements in economic evaluations of vaccination and develop standards for their subsequent measurement.

Identifying factors that can be used to assess a country's readiness to deploy a new vaccine or improve uptake of an underutilised vaccine: a scoping review.

OBJECTIVES: Identifying whether a country is ready to deploy a new vaccine or improve uptake of an existing vaccine requires knowledge of a diverse range of interdependent, context-specific factors. This scoping review aims to identify common themes that emerge across articles, which include tools or guidance that can be used to establish whether a country is ready to deploy a new vaccine or increase uptake of an underutilised vaccine. DESIGN: Scoping review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews guidelines. DATA SOURCES: Embase, CINAHL, Cochrane Library, Google Scholar, MEDLINE, PsycINFO and Web of Science were searched for articles published until 9 September 2023. Relevant articles were also identified through expert opinion. ELIGIBILITY CRITERIA: Articles published in any year or language that included tools or guidance to identify factors that influence a country's readiness to deploy a new or underutilised vaccine. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened records and performed data extraction. Findings were synthesised by conducting a thematic analysis. RESULTS: 38 articles met our inclusion criteria; these documents were created using methodologies including expert review panels and Delphi surveys and varied in terms of content and context-of-use. 12 common themes were identified relevant to a country's readiness to deploy a new or underutilised vaccine. These themes were as follows: (1) legal, political and professional consensus; (2) sociocultural factors and communication; (3) policy, guidelines and regulations; (4) financing; (5) vaccine characteristics and supply logistics; (6) programme planning; (7) programme monitoring and evaluation; (8) sustainable and integrated healthcare provision; (9) safety surveillance and reporting; (10) disease burden and characteristics; (11) vaccination equity and (12) human resources and training of professionals. CONCLUSIONS: This information has the potential to form the basis of a globally applicable evidence-based vaccine readiness assessment tool that can inform policy and immunisation programme decision-makers.

Identifying characteristics that enable resilient immunisation programmes: a scoping review.

OBJECTIVES: The COVID-19 pandemic highlighted the fragility of immunisation programmes and resulted in a significant reduction in vaccination rates, with increasing vaccine-preventable disease outbreaks consequently reported. These vulnerabilities underscore the importance of resilient immunisation programmes to ensure optimal performance during crises. To date, a framework for assessing immunisation programme resilience does not exist. We conducted a scoping review of immunisation programmes during times of crisis to identify factors that characterise resilient immunisation programmes, which may inform an Immunisation Programme Resilience Tool. DESIGN: Scoping review design followed the Arksey and O'Malley framework, and manuscript reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews guidelines. DATA SOURCES: CINAHL, CENTRAL, Embase, Google Scholar, MEDLINE, PsycINFO and Web of Science and databases were searched between 1 January 2011 and 2 September 2023. Citation searching of identified studies was also performed. ELIGIBILITY CRITERIA: We included primary empirical peer-reviewed studies that discussed the resilience of immunisation programme to crises, shocks or disruptions. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened records and performed data extraction. We extracted data on study location and design, crisis description, and resilience characteristics discussed, and identified evidence gaps in the literature. Findings were synthesised using tabulation and an evidence gap map. RESULTS: Thirty-seven studies met the eligibility criteria. These studies captured research conducted across six continents, with most concentrated in Africa, Asia and Europe. One study had a randomised controlled trial design, while 36 studies had observational designs (15 analytical and 21 descriptive). We identified five characteristics of resilient immunisation programmes drawing on the Health System Resilience Index (Integration, Awareness, Resource Availability and Access, Adaptiveness and Self-regulation) and several evidence gaps in the literature. CONCLUSIONS: To our knowledge, no immunisation programme resilience tool exists. We identified factors from the Health System Resilience Index coupled with factors identified through primary empirical evidence, which may inform development of an immunisation programme resilience tool.

Addressing an urgent global public health need: Strategies to recover routine vaccination during the COVID-19 pandemic.

Routine vaccination has been severely impacted by the COVID-19 pandemic, with 37% of countries reporting continuing disruptions to vaccination services into 2021. These programs have been faced with the challenges of achieving high vaccination coverage rates (VCRs), as well as identifying and vaccinating those who missed recommended doses since the pandemic began. Declines in VCRs, even for short periods, can lead to an increase in disease outbreaks, place additional pressure on health systems, and leave communities across the world at risk of death and disease from vaccine-preventable diseases.In the face of these disruptions, select governments are implementing promising approaches to address low VCRs, some of which represent innovative solutions to advance short-term, as well as longer-term program improvement. However, expanded action is urgently required to fully recover vaccination programs and strengthen vaccine system infrastructure. The COVID-19 pandemic provides a unique opportunity to modernize routine programs and corresponding infrastructure to meet today's and tomorrow's health challenges more effectively and efficiently. This can be achieved by prioritizing routine vaccination as an essential health service, improving access to vaccination across the life-course, strengthening data systems, ensuring sustainable immunization financing, and building confidence in vaccination.

Silent Consequences of COVID-19: Why It's Critical to Recover Routine Vaccination Rates Through Equitable Vaccine Policies and Practices.

In the United States, routine vaccination rates have plummeted across all age groups due to the COVID-19 pandemic, with our most vulnerable and under-served populations suffering the greatest declines. Returning to a "new normal" and recovering our nation's health and economy is of the utmost importance; however, there is a critical need to recover and protect communities against the spread of other vaccine-preventable diseases and outbreaks. While routine vaccination rates are slowly recovering for certain age groups, the introduction of COVID-19 vaccines adds complexities and challenges to recovery efforts. If not addressed, hard-won gains in routine vaccination may be lost, which could result in communities missing out on the social, economic, and health benefits offered by vaccinations.There is an urgent need to utilize evidence-based and innovative strategies to support both immediate and long-term efforts to recover, maintain, and sustain routine vaccination. Key short-term strategies include leveraging digital and mainstream media to drive awareness, coordinating across health and education sectors, utilizing centralized reminder recall, expanding access points to vaccination services, and elevating trusted voices for vaccination. In order to build back stronger, long-term strategies include enhancing immunization information systems, mitigating financial barriers to vaccination, investing in building vaccine confidence, and ensuring sustainable funding for immunization infrastructure.Annals "Online First" article.

Maternal vaccine knowledge in low- and middle-income countries-and why it matters.

Maternal vaccines have the potential to reduce the global burden of neonatal morbidity and mortality by accessing the infant immune system before a vaccine administered in childhood would be effective. Maternal vaccines for influenza, tetanus, and pertussis have been shown to reduce neonatal disease and mortality, and other candidate vaccines for group B streptococcus and respiratory syncytial virus are being developed to continue this trend. However, safe and effective maternal vaccines will only successfully reduce neonatal illness if mothers decide to receive them. Maternal knowledge, attitudes, and beliefs around vaccines are key determinants to vaccine acceptance or vaccine hesitancy, and yet this issue is often understudied in low and middle-income country settings. A deeper understanding of these factors and how they influence maternal decision-making will allow public health practitioners and global and national policymakers to design more effective interventions. Addressing barriers to immunization at the policy and programmatic levels such as mothers' knowledge, attitudes, and beliefs of maternal vaccines is essential to increasing vaccination rates at a global scale and reducing global vaccine-preventable neonatal deaths.

CTLA-4 blockade following relapse of malignancy after allogeneic stem cell transplantation is associated with T cell activation but not with increased levels of T regulatory cells.

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a key negative regulator of T cell activation and proliferation. Ipilimumab is a human monoclonal antibody that specifically blocks the binding of CTLA-4 to its ligand. To test the hypothesis that blockade of CTLA-4 by ipilimumab could augment graft-versus-malignancy (GVM) effects without a significant impact on graft-versus-host disease (GVHD), we conducted a phase I clinical trial of ipilimumab infusion in patients with relapsed malignancy following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Here, we report the analysis of peripheral blood T lymphocyte reconstitution, T regulatory cell (Treg) expression, and T cell activation markers after a single dose of ipilimumab in 29 patients. Peripheral blood samples were collected from all patients before and after ipilimumab infusion. Lymphocyte immunophenotyes, including levels of CD4(+)CD25(high) cells and T cell activation markers, were analyzed in all cases. Levels of CD4(+)CD25(high)Foxp3(+) cells and intracellular CTLA-4 in CD4(+) T cells also were evaluated in the last 11 cases. We found lower baseline levels of CD4(+) and CD45RO(+) T cells in patients compared with normal controls. More than 50% of the patients had abnormally low lymphocyte counts (CD4 or/and CD8 T cells), and some had no circulating B lymphocytes. The percentages of both CD4(+)CD25(high) and CD4(+)CD25(high)Foxp3(+) T cells were significantly higher in patients before ipilimumab infusion than in healthy donors. Twenty of 29 patients exhibited an elevated level of CD4(+)CD25(low) activated T cells at baseline, compared with only 3 of 26 healthy donors. Both CD4(+) and CD8(+) T lymphocyte counts were significantly increased after ipilimumab infusion. There was no consistent change in absolute lymphocyte count or in the number of T cells expressing the activation marker CD69. However, increases in CD4(+)CD25(low) T cells were seen in 20 of 29 patients and increases in CD4(+)HLA-DR(+) T cells were seen in the last 10 patients in the first 60 days after ipilimumab infusion. Although the percentages of both CD4(+)CD25(high) and CD4(+)CD25(high)Foxp3(+) T cells decreased significantly during the observation period, the absolute cell counts did not change. Intracellular CTLA-4 expression in CD4(+)CD25(lo/-) T cells increased significantly after ipilimumab infusion. We conclude that CTLA-4 blockade by a single infusion of ipilimumab increased CD4(+) and CD4(+)HLA-DR(+) T lymphocyte counts and intracellular CTLA-4 expression at the highest dose level. There was no significant change in Treg cell numbers after ipilimumab infusion. These data demonstrate that significant changes in T cell populations occur on exposure to a single dose of ipilimumab. Further studies with multiple doses are needed to explore this phenomenon further and to correlate changes in lymphocyte subpopulations with clinical events.

Descriptive analysis of immunization policy decision making in the Americas / Análisis descriptivo de la toma de decisión sobre políticas de vacunación en las Américas

OBJECTIVES: Reducing and eliminating vaccine-preventable diseases requires evidence-based and informed policy decision making. Critical to determining the functionality of the decision-making process for introduction of a new vaccine is understanding the role of the national immunization technical advisory group (ITAG) in each country. The aim of this study is to document the current situation of national level immunization policy decision making for use in the Pan American Health Organization (PAHO) ProVac Initiative. METHODS: A structured 66-variable questionnaire developed by the World Health Organization (WHO) in collaboration with the University of Ottawa was distributed to all WHO regions; it was composed of dichotomous, multiple-choice, and open-ended questions. Questionnaires were e-mailed or faxed to the six WHO regional offices and the offices distributed them to all member states. This paper analyzes surveys from the Americas as part of PAHO's ProVac Initiative. RESULTS: Twenty-nine countries of the Americas answered the survey. They conveyed that immunization policy making needed to be improved and further supported by organizations such as PAHO. Areas of improvement ranged from organization and technical support to strengthening capacity and infrastructure to improved coordination among stakeholders. This survey also highlighted a variety of ITAG processes that need further investigation. CONCLUSION: This survey supports the efforts of PAHO's ProVac Initiative to disseminate knowledge and best practices for an immunization policy decision-making framework through the development of clear definitions and guidelines. By highlighting each problem noted in this study, ProVac will assist countries in Latin America and the Caribbean to build national capacity for making evidence-based decisions about introduction of new vaccines.

OBJETIVOS: Para reducir y eliminar las enfermedades prevenibles por vacunación se requiere tomar decisiones basadas en datos científicos y una política informada. Con el fin de determinar la funcionalidad del proceso de toma de decisiones para introducir una nueva vacuna es vital comprender el papel de los grupos técnicos asesores nacionales sobre vacunación (GTAN) de cada país. En este trabajo se documenta la situación actual de la toma de decisión sobre políticas de vacunación a nivel nacional como insumo de la Iniciativa ProVac de la Organización Panamericana de la Salud (OPS). MÉTODOS: Se distribuyó a todas las regiones de la Organización Mundial de la Salud (OMS) un cuestionario estructurado con 66 variables, desarrollado por la OMS en colaboración con la Universidad de Ottawa, Canadá. El cuestionario contenía preguntas abiertas, dicotómicas y de selección múltiple y se envió por correo electrónico o fax a las seis oficinas regionales de la OMS y estas lo distribuyeron a todos los estados miembros. En este manuscrito se analizan las respuestas procedentes de las Américas, como parte de la Iniciativa ProVac de la OPS. RESULTADOS: Respondieron la encuesta 29 países de las Américas. Todos coincidieron en que la formulación de políticas de vacunación debe mejorar y se necesita más apoyo de organizaciones como la OPS. Las áreas que requieren mejoras van desde la organización y el apoyo técnico hasta el fortalecimiento de la capacidad y la infraestructura, y el perfeccionamiento de la coordinación entre los diferentes actores. También se destacan algunos procesos de los GTAN que requieren mayor investigación. CONCLUSIÓN: Esta encuesta apoya los esfuerzos de la iniciativa ProVac de la OPS para diseminar el conocimiento y las mejores prácticas para elaborar un marco de trabajo para la toma de decisiones sobre políticas de vacunación mediante el desarrollo de definiciones y directivas claras. Al poner de manifiesto cada problema observado ...

Descriptive analysis of immunization policy decision making in the Americas.

OBJECTIVES: Reducing and eliminating vaccine-preventable diseases requires evidence-based and informed policy decision making. Critical to determining the functionality of the decision-making process for introduction of a new vaccine is understanding the role of the national immunization technical advisory group (ITAG) in each country. The aim of this study is to document the current situation of national level immunization policy decision making for use in the Pan American Health Organization (PAHO) ProVac Initiative. METHODS: A structured 66-variable questionnaire developed by the World Health Organization (WHO) in collaboration with the University of Ottawa was distributed to all WHO regions; it was composed of dichotomous, multiple-choice, and open-ended questions. Questionnaires were e-mailed or faxed to the six WHO regional offices and the offices distributed them to all member states. This paper analyzes surveys from the Americas as part of PAHO's ProVac Initiative. RESULTS: Twenty-nine countries of the Americas answered the survey. They conveyed that immunization policy making needed to be improved and further supported by organizations such as PAHO. Areas of improvement ranged from organization and technical support to strengthening capacity and infrastructure to improved coordination among stakeholders. This survey also highlighted a variety of ITAG processes that need further investigation. CONCLUSION: This survey supports the efforts of PAHO's ProVac Initiative to disseminate knowledge and best practices for an immunization policy decision-making framework through the development of clear definitions and guidelines. By highlighting each problem noted in this study, ProVac will assist countries in Latin America and the Caribbean to build national capacity for making evidence-based decisions about introduction of new vaccines.