Evolution and Contribution of a Global Partnership against Measles and Rubella, 2001-2023.

This article describes the arc of global measles and rubella elimination since 2000 from the perspective of the founding partners of the Measles Initiative. The Measles Initiative was formed in 2001 as a partnership among the American Red Cross, the Centers for Disease Control and Prevention, UNICEF, the United Nations Foundation, and the World Health Organization with the aim to reduce measles deaths in low-income countries. Recognizing rubella as the leading infectious disease cause of congenital abnormalities globally and achievement of measles and rubella elimination in the region of the Americas, the partnership was renamed the Measles and Rubella Initiative (MRI) in 2012. The goals of the MRI were at least a 95% reduction in global measles mortality and elimination of measles and rubella in at least five of the six WHO regions. In January 2023, the membership of the partnership was expanded to include the Bill and Melinda Gates Foundation (BMGF) and Gavi the Vaccine Alliance, and its name changed to the IA2030 Measles and Rubella Partnership. We describe the role the partnership has had in measles partner effectiveness and its impact on measles and rubella disease burden, including how the partnership has strategically adapted to the evolving immunization landscape. We conclude with lessons learned regarding the role global partnerships can play in furthering the impact of disease control programs within the current global immunization environment.

The impact of disruptions caused by the COVID-19 pandemic on global polio eradication.

In early 2020, the COVID-19 pandemic led to substantial disruptions in global activities. The disruptions also included intentional and unintentional reductions in health services, including immunization campaigns against the transmission of wild poliovirus (WPV) and persistent serotype 2 circulating vaccine-derived poliovirus (cVDPV2). Building on a recently updated global poliovirus transmission and Sabin-strain oral poliovirus vaccine (OPV) evolution model, we explored the implications of immunization disruption and restrictions of human interactions (i.e., population mixing) on the expected incidence of polio and on the resulting challenges faced by the Global Polio Eradication Initiative (GPEI). We demonstrate that with some resumption of activities in the fall of 2020 to respond to cVDPV2 outbreaks and full resumption on January 1, 2021 of all polio immunization activities to pre-COVID-19 levels, the GPEI could largely mitigate the impact of COVID-19 to the delays incurred. The relative importance of reduced mixing (leading to potentially decreased incidence) and reduced immunization (leading to potentially increased expected incidence) depends on the timing of the effects. Following resumption of immunization activities, the GPEI will likely face similar barriers to eradication of WPV and elimination of cVDPV2 as before COVID-19. The disruptions from the COVID-19 pandemic may further delay polio eradication due to indirect effects on vaccine and financial resources.

Serotype 2 oral poliovirus vaccine (OPV2) choices and the consequences of delaying outbreak response.

The Global Polio Eradication Initiative (GPEI) faces substantial challenges with managing outbreaks of serotype 2 circulating vaccine-derived polioviruses (cVDPV2s) in 2021. A full five years after the globally coordinated removal of serotype 2 oral poliovirus vaccine (OPV2) from trivalent oral poliovirus vaccine (tOPV) for use in national immunization programs, cVDPV2s did not die out. Since OPV2 cessation, responses to outbreaks caused by cVDPV2s mainly used serotype 2 monovalent OPV (mOPV2) from a stockpile. A novel vaccine developed from a genetically stabilized OPV2 strain (nOPV2) promises to potentially facilitate outbreak response with lower prospective risks, although its availability and properties in the field remain uncertain. Using an established global poliovirus transmission model and building on a related analysis that characterized the impacts of disruptions in GPEI activities caused by the COVID-19 pandemic, we explore the implications of trade-offs associated with delaying outbreak response to avoid using mOPV2 by waiting for nOPV2 availability (or equivalently, delayed responses waiting for national validation of meeting the criteria for nOPV2 initial use). Consistent with prior modeling, responding as quickly as possible with available mOPV2 promises to reduce the expected burden of disease in the outbreak population and to reduce the chances for the outbreak virus to spread to other areas. Delaying cVDPV2 outbreak response (e.g., modeled as no response January-June 2021) to wait for nOPV2 can considerably increase the total expected cases (e.g., by as many as 1,300 cVDPV2 cases in the African region during 2021-2023) and increases the likelihood of triggering the need to restart widescale preventive use of an OPV2-containing vaccine in national immunization programs that use OPV. Countries should respond to any cVDPV2 outbreaks quickly with rounds that achieve high coverage using any available OPV2, and plan to use nOPV2, if needed, once it becomes widely available based on evidence that it is as effective but safer in populations than mOPV2.

Modeling Poliovirus Surveillance and Immunization Campaign Quality Monitoring Costs for Pakistan and Afghanistan for 2019-2023.

BACKGROUND: The Global Polio Eradication Initiative (GPEI) Strategic Plan for 2019-2023 includes commitments to monitor the quality of immunization campaigns using lot quality assurance sampling surveys (LQAS) and to support poliovirus surveillance in Pakistan and Afghanistan. METHODS: We analyzed LQAS and poliovirus surveillance data between 2016 and 2020, which included both acute flaccid paralysis (AFP) case-based detection and the continued expansion of environmental surveillance (ES). Using updated estimates for unit costs, we explore the costs of different options for future poliovirus monitoring and surveillance for Pakistan and Afghanistan. RESULTS: The relative value of the information provided by campaign quality monitoring and surveillance remains uncertain and depends on the design, implementation, and performance of the systems. Prospective immunization campaign quality monitoring (through LQAS) and poliovirus surveillance will require tens of millions of dollars each year for the foreseeable future for Pakistan and Afghanistan. CONCLUSIONS: LQAS campaign monitoring as currently implemented in Pakistan and Afghanistan provides limited and potentially misleading information about immunization quality. AFP surveillance in Pakistan and Afghanistan provides the most reliable evidence of transmission, whereas ES provides valuable supplementary information about the extent of transmission in the catchment areas represented at the time of sample collection.

Updated Characterization of Poliovirus Transmission in Pakistan and Afghanistan and the Impacts of Different Outbreak Response Vaccine Options.

BACKGROUND: Pakistan and Afghanistan remain the only reservoirs of wild poliovirus transmission. Prior modeling suggested that before the coronavirus disease 2019 (COVID-19) pandemic, plans to stop the transmission of serotype 1 wild poliovirus (WPV1) and persistent serotype 2 circulating vaccine-derived poliovirus (cVDPV2) did not appear on track to succeed. METHODS: We updated an existing poliovirus transmission and Sabin-strain oral poliovirus vaccine (OPV) evolution model for Pakistan and Afghanistan to characterize the impacts of immunization disruptions and restrictions on human interactions (ie, population mixing) due to the COVID-19 pandemic. We also consider different options for responding to outbreaks and for preventive supplementary immunization activities (SIAs). RESULTS: The modeling suggests that with some resumption of activities in the fall of 2020 to respond to cVDPV2 outbreaks and full resumption on 1 January 2021 of all polio immunization activities to pre-COVID-19 levels, Pakistan and Afghanistan would remain off-track for stopping all transmission through 2023 without improvements in quality. CONCLUSIONS: Using trivalent OPV (tOPV) for SIAs instead of serotype 2 monovalent OPV offers substantial benefits for ending the transmission of both WPV1 and cVDPV2, because tOPV increases population immunity for both serotypes 1 and 2 while requiring fewer SIA rounds, when effectively delivered in transmission areas.

Global Transmission of Live Polioviruses: Updated Dynamic Modeling of the Polio Endgame.

Nearly 20 years after the year 2000 target for global wild poliovirus (WPV) eradication, live polioviruses continue to circulate with all three serotypes posing challenges for the polio endgame. We updated a global differential equation-based poliovirus transmission and stochastic risk model to include programmatic and epidemiological experience through January 2020. We used the model to explore the likely dynamics of poliovirus transmission for 2019-2023, which coincides with a new Global Polio Eradication Initiative Strategic Plan. The model stratifies the global population into 72 blocks, each containing 10 subpopulations of approximately 10.7 million people. Exported viruses go into subpopulations within the same block and within groups of blocks that represent large preferentially mixing geographical areas (e.g., continents). We assign representative World Bank income levels to the blocks along with polio immunization and transmission assumptions, which capture some of the heterogeneity across countries while still focusing on global poliovirus transmission dynamics. We also updated estimates of reintroduction risks using available evidence. The updated model characterizes transmission dynamics and resulting polio cases consistent with the evidence through 2019. Based on recent epidemiological experience and prospective immunization assumptions for the 2019-2023 Strategic Plan, the updated model does not show successful eradication of serotype 1 WPV by 2023 or successful cessation of oral poliovirus vaccine serotype 2-related viruses.

Updated Characterization of Post-OPV Cessation Risks: Lessons from 2019 Serotype 2 Outbreaks and Implications for the Probability of OPV Restart.

After the globally coordinated cessation of any serotype of oral poliovirus vaccine (OPV), some risks remain from undetected, existing homotypic OPV-related transmission and/or restarting transmission due to several possible reintroduction risks. The Global Polio Eradication Initiative (GPEI) coordinated global cessation of serotype 2-containing OPV (OPV2) in 2016. Following OPV2 cessation, the GPEI and countries implemented activities to withdraw all the remaining trivalent OPV, which contains all three poliovirus serotypes (i.e., 1, 2, and 3), from the supply chain and replace it with bivalent OPV (containing only serotypes 1 and 3). However, as of early 2020, monovalent OPV2 use for outbreak response continues in many countries. In addition, outbreaks observed in 2019 demonstrated evidence of different types of risks than previously modeled. We briefly review the 2019 epidemiological experience with serotype 2 live poliovirus outbreaks and propose a new risk for unexpected OPV introduction for inclusion in global modeling of OPV cessation. Using an updated model of global poliovirus transmission and OPV evolution with and without consideration of this new risk, we explore the implications of the current global situation with respect to the likely need to restart preventive use of OPV2 in OPV-using countries. Simulation results without this new risk suggest OPV2 restart will likely need to occur (81% of 100 iterations) to manage the polio endgame based on the GPEI performance to date with existing vaccine tools, and with the new risk of unexpected OPV introduction the expected OPV2 restart probability increases to 89%. Contingency planning requires new OPV2 bulk production, including genetically stabilized OPV2 strains.

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.

Modeling Poliovirus Transmission in Pakistan and Afghanistan to Inform Vaccination Strategies in Undervaccinated Subpopulations.

Due to security, access, and programmatic challenges in areas of Pakistan and Afghanistan, both countries continue to sustain indigenous wild poliovirus (WPV) transmission and threaten the success of global polio eradication and oral poliovirus vaccine (OPV) cessation. We fitted an existing differential-equation-based poliovirus transmission and OPV evolution model to Pakistan and Afghanistan using four subpopulations to characterize the well-vaccinated and undervaccinated subpopulations in each country. We explored retrospective and prospective scenarios for using inactivated poliovirus vaccine (IPV) in routine immunization or supplemental immunization activities (SIAs). The undervaccinated subpopulations sustain the circulation of serotype 1 WPV and serotype 2 circulating vaccine-derived poliovirus. We find a moderate impact of past IPV use on polio incidence and population immunity to transmission mainly due to (1) the boosting effect of IPV for individuals with preexisting immunity from a live poliovirus infection and (2) the effect of IPV-only on oropharyngeal transmission for individuals without preexisting immunity from a live poliovirus infection. Future IPV use may similarly yield moderate benefits, particularly if access to undervaccinated subpopulations dramatically improves. However, OPV provides a much greater impact on transmission and the incremental benefit of IPV in addition to OPV remains limited. This study suggests that despite the moderate effect of using IPV in SIAs, using OPV in SIAs remains the most effective means to stop transmission, while limited IPV resources should prioritize IPV use in routine immunization.

Contribution of Global Polio Eradication Initiative-Funded Personnel to the Strengthening of Routine Immunization Programs in the 10 Focus Countries of the Polio Eradication and Endgame Strategic Plan.

Background: The Polio Eradication and Endgame Strategic Plan (PEESP) established a target that at least 50% of the time of personnel receiving funding from the Global Polio Eradication Initiative (GPEI) for polio eradication activities (hereafter, "GPEI-funded personnel") should be dedicated to the strengthening of immunization systems. This article describes the self-reported profile of how GPEI-funded personnel allocate their time toward immunization goals and activities beyond those associated with polio, the training they have received to conduct tasks to strengthen routine immunization systems, and the type of tasks they have conducted. Methods: A survey of approximately 1000 field managers of frontline GPEI-funded personnel was conducted by Boston Consulting Group in the 10 focus countries of the PEESP during 2 phases, in 2013 and 2014, to determine time allocation among frontline staff. Country-specific reports on the training of GPEI-funded personnel were reviewed, and an analysis of the types of tasks that were reported was conducted. Results: A total of 467 managers responded to the survey. Forty-seven percent of the time (range, 23%-61%) of GPEI-funded personnel was dedicated to tasks related to strengthening immunization programs, other than polio eradication. Less time was spent on polio-associated activities in countries that had already interrupted wild poliovirus (WPV) transmission, compared with findings for WPV-endemic countries. All countries conducted periodic trainings of the GPEI-funded personnel. The types of non-polio-related tasks performed by GPEI-funded personnel varied among countries and included surveillance, microplanning, newborn registration and defaulter tracing, monitoring of routine immunization activities, and support of district immunization task teams, as well as promotion of health behaviors, such as clean-water use and good hygiene and sanitation practices. Conclusion: In all countries, GPEI-funded personnel perform critical tasks in the strengthening of routine immunization programs and the control of measles and rubella. In certain countries with very weak immunization systems, GPEI-funded personnel provide critical support for the immunization programs, and sudden discontinuation of their employment would potentially disrupt the immunization programs in their countries and create a setback in capacity and effectiveness that would put children at higher risk for vaccine-preventable diseases.

Polio Legacy in Action: Using the Polio Eradication Infrastructure for Measles Elimination in Nigeria-The National Stop Transmission of Polio Program.

From 2012 to date, Nigeria has been the focus of intensified polio eradication efforts. Large investments made by multiple partner organizations and the federal Ministry of Health to support strategies and resources, including personnel, for increasing vaccination coverage and improved performance monitoring paid off, as the number of wild poliovirus (WPV) cases detected in Nigeria were reduced significantly, from 122 in 2012 to 6 in 2014. No WPV cases were detected in Nigeria in 2015 and as at March 2017, only 4 WPV cases had been detected. Given the momentum gained toward polio eradication, these resources seem well positioned to help advance other priority health agendas in Nigeria, particularly the control of vaccine-preventable diseases, such as measles. Despite implementation of mass measles vaccination campaigns, measles outbreaks continue to occur regularly in Nigeria, leading to high morbidity and mortality rates for children <5 years of age. The National Stop Transmission of Polio (NSTOP) program was collaboratively established in 2012 to create a network of staff working at national, state, and district levels in areas deemed high risk for vaccine-preventable disease outbreaks. As an example of how the polio legacy can create long-lasting improvements to public health beyond polio, the Centers for Disease Control and Prevention will transition >180 NSTOP officers to provide technical experience to improve measles surveillance, routine vaccination coverage, and outbreak investigation and response in high-risk areas.

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.

Addressing the Challenges and Opportunities of the Polio Endgame: Lessons for the Future.

The Global Commission for the Certification of the Eradication of Poliomyelitis certified the eradication of type 2 poliovirus in September 2015, making type 2 poliovirus the first human pathogen to be eradicated since smallpox. The eradication of type 2 poliovirus, the absence of detection of type 3 poliovirus worldwide since November 2012, and cornering type 1 poliovirus to only a few geographic areas of 3 countries has enabled implementation of the endgame of polio eradication which calls for a phased withdrawal of oral polio vaccine beginning with the type 2 component, introduction of inactivated poliovirus vaccine, strengthening of routine immunization in countries with extensive polio resources, and initiating activities to transition polio resources, program experience, and lessons learned to other global health initiatives. This supplement focuses on efforts by global partners to successfully launch polio endgame activities to permanently secure and sustain the enormous gains of polio eradication forever.

Adapting Nepal's polio eradication programme.

PROBLEM: Many countries have weak disease surveillance and immunization systems. The elimination of polio creates an opportunity to use staff and assets from the polio eradication programme to control other vaccine-preventable diseases and improve disease surveillance and immunization systems. APPROACH: In 2003, the active surveillance system of Nepal's polio eradication programme began to report on measles and neonatal tetanus cases. Japanese encephalitis and rubella cases were added to the surveillance system in 2004. Staff from the programme aided the development and implementation of government immunization policies, helped launch vaccination campaigns, and trained government staff in reporting practices and vaccine management. LOCAL SETTING: Nepal eliminated indigenous polio in 2000, and controlled outbreaks caused by polio importations between 2005 and 2010. RELEVANT CHANGES: In 2014, the surveillance activities had expanded to 299 sites, with active surveillance for measles, rubella and neonatal tetanus, including weekly visits from 15 surveillance medical officers. Sentinel surveillance for Japanese encephalitis consisted of 132 sites. Since 2002, staff from the eradication programme have helped to introduce six new vaccines and helped to secure funding from Gavi, the Vaccine Alliance. Staff have also assisted in responding to other health events in the country. LESSON LEARNT: By expanding the activities of its polio eradication programme, Nepal has improved its surveillance and immunization systems and increased vaccination coverage of other vaccine-preventable diseases. Continued donor support, a close collaboration with the Expanded Programme on Immunization, and the retention of the polio eradication programme's skilled workforce were important for this expansion.