How ready was the US vaccination infrastructure and network of immunization information systems for COVID-19 vaccination campaigns: Recommendations to strengthen the routine vaccination program and prepare for the next pandemic.

Coronavirus disease 2019 (COVID-19) pandemic vaccination campaigns globally have been unlike any effort in history. In the United States, the success of these efforts, in part, has hinged on the timely capture and reporting of an unprecedented amount of data from a significantly greater number of administering providers than for routine vaccinations. The pandemic response has highlighted the need to explore the status and value of vaccination data as the critical glue that connects all aspects of the upstream US vaccine development and downstream vaccination delivery system. In this review, we examine immunization information systems and the role that data and staffing play in pandemic responses. We offer three strategic recommendations-regarding funding, expanded provider enrollment, and data reporting-informed by a literature review, a survey and focus group from a convenience sample of 22 immunization jurisdictions, and the vision for enhanced data flow to improve future pandemic responses and routine vaccination.

Current Challenges and Future Possibilities for Immunization Information Systems.

Immunizations have proven to be an important tool for public health and for reducing the impact of vaccine preventable diseases. To realize the maximum benefits of immunizations, a coordinated effort between public policy, health care providers and health systems is required to increase vaccination coverage and to ensure high-quality data are available to inform clinical and public health interventions. Immunization information systems (IIS) are confidential, population-based, computerized databases that record all immunization doses administered by participating providers to persons residing within a given geopolitical area. The key output of an IIS is high-quality data for use in targeting and monitoring immunization program activities and providing clinical decision support at the point of care. To be truly effective, IISs need to form a nationwide network and repository of immunization data. Since the early 2000s Centers for Disease Control and Prevention has made strides to help IIS move toward a nationwide network through efforts focused on improving infrastructure and functionality, such as the IIS Minimum Functional Standards, and the IIS Annual Report, a self-reported data collection of IIS progress toward achieving the functional standards. While these efforts have helped immunization programs achieve more functional standards, there is a need to shift focus from infrastructure and functionality improvements to high data quality through objective measurement of IIS performance and evaluating critical outcomes. Additionally, realizing the vision of a nationwide repository of high-quality immunization data requires tackling the many challenges that impact data quality and availability including those related to policy, data sharing, data use, aging IIS technology, sustainability, and participation in the IIS. This paper describes the current state of IIS in the United States, critical challenges impacting the quality of data in IIS, and potential components of a future IIS model to address these challenges.

Measurement and improvement as a model to strengthen immunization information systems and overcome data gaps.

BACKGROUND: IIS are important tools in the public health system and exist to improve and protect the nation's health from vaccine-preventable diseases. A network of 62 independent state, territorial, and jurisdictional immunization information systems (IIS) are operated within the United States. These systems are relied upon to implement an increasingly complex vaccination schedule, consolidate and create comprehensive immunization records, as well as monitor vaccine safety, efficacy, and support vaccine delivery. Despite their importance and necessity, the number of varying systems, coupled with jurisdictional policy and resource limitations, presents challenges with standardization, interoperability, data exchange, and the capture of complete immunization records. In partnership with the Centers for Disease Control (CDC) and IIS partners, the American Immunization Registry Association (AIRA) instituted its Measurement and Improvement (M&I) Initiative in 2015 as an innovative effort to evaluate and increase alignment of IIS with national functional standards. Lessons and strategies can be adapted for broader implementation as global systems develop methods to better achieve 2030 Sustainable Development Goal (SDG) targets, particularly related to global population health and infrastructure. METHODS: AIRA works closely with its partners to propose, vet, and refine processes and measures that can be compared across IIS, resulting in a uniform, standardized approach for measurement. The M&I Initiative is conducted as a third-party, independent evaluation through AIRA connecting with IIS pre-production systems to test the IIS response to test messages and measures across multiple content areas prioritized by the IIS community. The process includes three stages: 1) Testing and Discovery, 2) Assessment, and 3) Validation. Content areas currently evaluated include clinical decision support, interoperability transport, HL7 submission/acknowledgement, HL7 message query/response, and data quality. Testing is performed using the AIRA-developed Aggregate Analysis Reporting Tool (AART), an electronic testing tool and user interface specifically designed to compile and visualize results from the measures and tests. RESULTS: The M&I Initiative is voluntary with 86 percent (50/58) of the IIS programs targeted for measurement participating as of Spring 2020. To date, AIRA has actively measured standards alignment and published data on Validation in the first three content areas of Transport, Submission/Acknowledgement, and Query/Response. Thirty-one individual IIS have been validated in at least two of these three content areas. The number of IIS meeting one primary Transport measure has increased from 19 to 39 in three years, an increase of 105 percent. The number of IIS who were able to process the submission of a correctly formatted full immunization record for a patient jumped from 17 to 34, a 200 percent increase from baseline. Similarly, the number of IIS sending standards-conformant HL7 Acknowledgment messages has increased fourteen-fold since measurement began in 2017. The number of IIS who were able to process and respond to a query requesting a patient's evaluated immunization record and forecast increased from nine to 42, a 367 percent increase from baseline. Within the first two quarters of assessment, the percentage of IIS meeting the CDS measures aimed at supporting IIS alignment with ACIP recommendations increased 15 percent from baseline. CONCLUSION: The M&I initiative has helped to reduce variability across IIS and strengthen immunization data in IIS that is more complete, accurate, and can be utilized with confidence. The successes and experience offer an innovative model that could be adapted to standardize measures of success and data-sharing capabilities across global borders, particularly of value in achieving SDGs aimed at ensuring healthy lives and promoting well-being for all ages through strengthened immunization systems.

Immunization information systems to increase vaccination rates: a community guide systematic review.

CONTEXT: Immunizations are the most effective way to reduce incidence of vaccine-preventable diseases. Immunization information systems (IISs) are confidential, population-based, computerized databases that record all vaccination doses administered by participating providers to people residing within a given geopolitical area. They facilitate consolidation of vaccination histories for use by health care providers in determining appropriate client vaccinations. Immunization information systems also provide aggregate data on immunizations for use in monitoring coverage and program operations and to guide public health action. EVIDENCE ACQUISITION: Methods for conducting systematic reviews for the Guide to Community Preventive Services were used to assess the effectiveness of IISs. Reviewed evidence examined changes in vaccination rates in client populations or described expanded IIS capabilities related to improving vaccinations. The literature search identified 108 published articles and 132 conference abstracts describing or evaluating the use of IISs in different assessment categories. EVIDENCE SYNTHESIS: Studies described or evaluated IIS capabilities to (1) create or support effective interventions to increase vaccination rates, such as client reminder and recall, provider assessment and feedback, and provider reminders; (2) determine client vaccination status to inform decisions by clinicians, health care systems, and schools; (3) guide public health responses to outbreaks of vaccine-preventable disease; (4) inform assessments of vaccination coverage, missed vaccination opportunities, invalid dose administration, and disparities; and (5) facilitate vaccine management and accountability. CONCLUSIONS: Findings from 240 articles and abstracts demonstrate IIS capabilities and actions in increasing vaccination rates with the goal of reducing vaccine-preventable disease.

How school nurses can benefit from immunization information systems: information exchange to keep students in school and ready to learn.

Recorded and retrievable information from state immunization information systems (IIS)--previously known as immunization registries--benefits schools, students, families, state and local immunization programs, and the medical home. The National Association of School Nurses (NASN), the National Association of County and City Health Officials (NACCHO), the Association of State and Territorial Health Officials (ASTHO), and the American Immunization Registry Association (AIRA) support state IIS as a way to facilitate immunization compliance, prevent immunization duplications, and sustain high immunization rates. There is much variability from state to state on who can access and/or input data into the IIS. School nurses need to know they can pick up the phone and contact their state IIS, and state IIS personnel need to know that school nurses desire full access to their state registry to view records and record vaccines administered and/or documented by families.

Membrane-type 1 matrix metalloproteinase regulates cell migration during zebrafish gastrulation: evidence for an interaction with non-canonical Wnt signaling.

Key to invasiveness is the ability of tumor cells to modify the extracellular matrix, become motile, and engage in directed migration towards the vasculature. One significant protein associated with metastatic progression is membrane-type 1 matrix metalloproteinase (MT1-MMP/MMP14). How MMP14 activity is coordinated with other signaling pathways to regulate cell migration in vivo is largely unknown. Here we have used zebrafish embryogenesis as a model to understand the potential relationship between MMP14-dependent pericellular proteolysis, cell polarity, and motility. Knockdown of zebrafish Mmp14 function disrupted gastrulation convergence and extension cell movements and craniofacial morphogenesis. Using time-lapse imaging and morphometric analyses, we show that Mmp14 is required for proper cell polarity underlying the directed migration of mesodermal cells during gastrulation. We have identified a genetic interaction between mmp14 and non-canonical Wnt signaling, a pathway that also regulates cell polarity in embryonic tissues and is increasingly being linked with tumor cell migration. Finally, we demonstrate that Van Gogh-like 2, a key regulator of the non-canonical Wnt pathway, co-localizes with MMP14 and becomes redistributed towards the leading edge of polarized human cancer cells. Together, our results support the notion that pathways regulating pericellular proteolysis and cell polarity converge to promote efficient cell migration.

Epidermal growth factor receptor signaling regulates Bax and Bcl-w expression and apoptotic responses during intestinal adaptation in mice.

BACKGROUND & AIMS: Normal intestinal adaptation to massive small-bowel resection requires intact epidermal growth factor receptor signaling and consists of increased enterocyte proliferation and apoptosis. Although emphasis has been placed on understanding the regulation of proliferation, few studies have evaluated the mechanism and contribution of apoptosis to the adaptation response. We sought to test the hypothesis that epidermal growth factor receptor signaling regulates specific Bcl-2 family members (Bax and Bcl-w) to direct apoptosis and adaptation after massive small-bowel resection. METHODS: Laser capture microdissection microscopy permitted measurement of Bax and Bcl-w messenger RNA expression in crypt and villus enterocytes in control conditions and under epidermal growth factor receptor-inhibited (waved-2 mice) or stimulated (epidermal growth factor transgenic mice) conditions after a 50% small-bowel resection or sham operation. Resection-induced adaptation was then studied in Bax-null and Bcl-w-null mice under control circumstances and after epidermal growth factor receptor stimulation. RESULTS: When compared with Bcl-w, the most significant expression changes were observed with Bax and took place within crypt enterocytes. Epidermal growth factor receptor stimulation resulted in a decreased ratio of Bax to Bcl-w expression and decreased rates of apoptosis. Bax-null mice had no apoptosis response to small-bowel resection and displayed an amplified adaptation response to the administration of epidermal growth factor. Bcl-w-null mice had poor survival and impaired adaptation to small-bowel resection, an effect that was rescued by crossbreeding these mice with epidermal growth factor transgenic mice. CONCLUSIONS: The crypt expression of Bax and Bcl-w is influenced by epidermal growth factor receptor signaling and is key for the regulation of apoptosis. Epidermal growth factor receptor stimulation, coupled with apoptosis inhibition, may provide a novel strategy to amplify adaptation responses in patients after massive intestinal loss.