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Since 2013, wild poliovirus (WPV) transmission occurred only for type 1 (WPV1). Following several years of increasing reported incidence (2017-2019) and programmatic disruptions caused by COVID-19 (early 2020), Pakistan and Afghanistan performed a large number of supplementary immunization activities (late 2020-2021). This increased intensity of immunization, following widespread transmission, substantially decreased WPV1 cases and positive environmental samples during 2021. Modeling the potential for undetected circulation of WPV1 after apparent interruption can support regional and global decisions about certification of the eradication of indigenous WPV1 transmission. We apply a stochastic model to estimate the confidence about no circulation (CNC) of WPV1 in Pakistan and Afghanistan as a function of time since the last reported case and/or positive environmental sample. Exploration of different assumptions about surveillance quality suggests a range for CNC for WPV1 as a function of time since the last positive surveillance signal, and supports the potential use of a time with no evidence of transmission of less than 3 years as sufficient to assume die out in the context of good acute flaccid paralysis (AFP) surveillance. We show high expected CNC based on AFP surveillance data alone, even with imperfect surveillance and some use of inactivated poliovirus vaccine masking the ability of AFP surveillance to detect transmission. Ensuring high quality AFP and environmental surveillance may substantially shorten the time required to reach high CNC. The time required for high CNC depends on whether immunization activities maintain high population immunity and the quality of surveillance data.

BACKGROUND: Multiple vaccine options are available for polio prevention and risk management. Integrated global risk, economic, and poliovirus transmission modeling provides a tool to explore the dynamics of ending all use of one or more poliovirus vaccines to simplify the polio eradication endgame. RESEARCH DESIGN AND METHODS: With global reported cases of poliomyelitis trending higher since 2016, we apply an integrated global model to simulate prospective vaccine policies and strategies for OPV-using countries starting with initial conditions that correspond to the epidemiological poliovirus transmission situation at the beginning of 2022. RESULTS: Abruptly ending all OPV use in 2023 and relying only on IPV to prevent paralysis with current routine immunization coverage would lead to expected reestablished endemic transmission of poliovirus types 1 and 2, and approximately 150,000 expected cases of poliomyelitis per year. Alternatively, if OPV-using countries restart trivalent OPV (tOPV) use for all immunization activities and end IPV use, the model shows the lowest anticipated annual polio cases and lowest costs. CONCLUSIONS: Poor global risk management and coordination of OPV cessation remain a critical failure mode for the polio endgame, and national and global decision makers face difficult choices due to multiple available polio vaccine options and immunization strategies.

Background Investments in national immunization programs and the Global Polio Eradication Initiative (GPEI) have resulted in substantial reductions in paralytic polio worldwide. However, cases prevented because of investments in immunization programs and GPEI remain incompletely characterized. Methods Using a global model that integrates polio transmission, immunity, and vaccine dynamics, we provide estimates of polio incidence and numbers of paralytic cases prevented. We compare the results with reported cases and estimates historically published by the World Health Organization. Results We estimate that the existence and use of polio vaccines prevented 5 million cases of paralytic polio for 1960–1987 and 24 million cases worldwide for 1988–2021 compared to a counterfactual world with no polio vaccines. Since the 1988 resolution to eradicate polio, our estimates suggest GPEI prevented 2.5–6 million cases of paralytic polio compared to counterfactual worlds without GPEI that assume different levels of intensity of polio vaccine use in routine immunization programs. Conclusions Analysis of historical cases provides important context for understanding and communicating the benefits of investments made in polio eradication. Prospective studies will need to explore the expected benefits of future investments, the outcomes of which will depend on whether and when polio is globally eradicated.

Pakistan and Afghanistan pose risks for international transmission of polioviruses as the last global reservoir for wild poliovirus type 1 (WPV1) and a reservoir for type 2 circulating vaccine-derived polioviruses (cVDPV2s). Widespread transmission of WPV1 and cVDPV2 in 2019-2020 and resumption of intensive supplemental immunization activities (SIAs) in 2020-2021 using oral poliovirus vaccine (OPV) led to decreased transmission of WPV1 and cVDPV2 as of the end of 2021. Using an established dynamic disease transmission model, we explore multiple bounding scenarios with varying intensities of SIAs using bivalent OPV (bOPV) and/or trivalent tOPV (tOPV) to characterize potential die out of transmission. This analysis demonstrates potential sets of actions that may lead to elimination of poliovirus transmission in Pakistan and/or Afghanistan. Some modeled scenarios suggest that Pakistan and Afghanistan could increase population immunity to levels high enough to eliminate transmission, and if maintained, achieve WPV1 and cVDPV2 elimination as early as 2022. This requires intensive and proactive OPV SIAs to prevent transmission, instead of surveillance followed by reactive outbreak response. The reduction of cases observed in 2021 may lead to a false sense of security that polio has already or soon will die out on its own, but relaxation of immunization activities runs the risk of lowering population immunity to, or below, the minimum die-out threshold such that transmission continues. Transmission modeling may play a key role in managing expectations and supporting future modeling about the confidence of no virus circulation in anticipation of global certification decisions.

Background: The polio eradication endgame continues to increase in complexity. With polio cases caused by wild poliovirus type 1 and circulating vaccine-derived polioviruses of all three types (1, 2 and 3) reported in 2022, the number, formulation, and use of poliovirus vaccines poses challenges for national immunization programs and vaccine suppliers. Prior poliovirus transmission modeling of globally-coordinated type-specific cessation of oral poliovirus vaccine (OPV) assumed creation of Sabin monovalent OPV (mOPV) stockpiles for emergencies and explored the potential need to restart OPV if the world reached a specified cumulative threshold number of cases after OPV cessation. Methods: We document the actual experience of type 2 OPV (OPV2) cessation and reconsider prior modeling assumptions related to OPV restart. We develop updated decision trees of national immunization options for poliovirus vaccines considering different possibilities for OPV restart. Results: While OPV restart represented a hypothetical situation for risk management and contingency planning to support the 2013-2018 Global Polio Eradication Initiative (GPEI) Strategic Plan, the actual epidemiological experience since OPV2 cessation raises questions about what, if any, trigger(s) could lead to restarting the use of OPV2 in routine immunization and/or plans for potential future restart of type 1 and 3 OPV after their respective cessation. The emergency use listing of a genetically stabilized novel type 2 OPV (nOPV2) and continued evaluation of nOPV for types 1 and/or 3 add further complexity by increasing the combinations of possible OPV formulations for OPV restart. Conclusions: Expanding on a 2019 discussion of the logistical challenges and implications of restarting OPV, we find a complex structure of the many options and many issues related to OPV restart decisions and policies as of early 2023. We anticipate many challenges for forecasting prospective vaccine supply needs during the polio endgame due to increasing potential combinations of poliovirus vaccine choices.

The polio endgame remains complicated, with many questions about future polio vaccines and national immunization policies. We simulated possible future poliovirus vaccine routine immunization policies for countries stratified by World Bank Income Levels and estimated the expected costs and cases using an updated integrated dynamic poliovirus transmission, stochastic risk, and economic model. We consider two reference cases scenarios: one that achieves the eradication of all wild polioviruses (WPVs) by 2023 and one in which serotype 1 WPV (WPV1) transmission continues. The results show that the addition of inactivated poliovirus vaccine (IPV) to routine immunization in all countries substantially increased the expected costs of the polio endgame, without substantially increasing its expected health or economic benefits. Adding a second dose of IPV to the routine immunization schedules of countries that currently include a single IPV dose further increases costs and does not appear economically justified in the reference case that does not stop WPV transmission. For the reference case that includes all WPV eradication, adding a second IPV dose at the time of successful OPV cessation represents a cost-effective option. The risks and costs of needing to restart oral poliovirus vaccine (OPV) use change the economics of the polio endgame, although the time horizon used for modeling impacts the overall economic results. National health leaders will want to consider the expected health and economic net benefits of their national polio vaccine strategies recognizing that preferred strategies may differ.

Despite a strong global commitment, polio eradication efforts continue now more than 30 years after the 1988 World Health Assembly resolution that established the Global Polio Eradication Initiative (GPEI), and 20 years after the original target of the year 2000. Prior health economic analyses estimated incremental net benefits of the GPEI of 40–50 billion in 2008 US dollars (US$2008, equivalent to 48–59 billion US$2019), assuming the achievement of polio eradication by 2012. Given the delays in achieving polio eradication and increased costs, we performed an updated economic analysis of the GPEI using an updated integrated global model, and considering the GPEI trajectory as of the beginning of 2020. Applying similar methods and assuming eradication achievement in 2023, we estimate incremental net benefits of the GPEI of 28 billion US$2019, which falls below the prior estimate. Delays in achieving polio eradication combined with the widescale introduction of relatively expensive inactivated poliovirus vaccine (IPV) significantly increased the costs of the GPEI and make it less cost-effective, although the GPEI continues to yield expected incremental net benefits at the global level when considered over the time horizon of 1988–2029. The overall health and financial benefits of the GPEI will depend on whether and when the GPEI can achieve its goals, when eradication occurs, the valuation method applied, and the path dependence of the actions taken. Reduced expected incremental net benefits of the GPEI and the substantial economic impacts of the COVID-19 pandemic pose large financial risks for the GPEI.

Despite exhaustive and fully-financed plans to manage the risks of globally coordinated cessation of oral poliovirus vaccine (OPV) containing type 2 (OPV2) prior to 2016, as of 2022, extensive, continued transmission of circulating vaccine-derived polioviruses (cVDPVs) type 2 (cVDPV2) remains. Notably, cumulative cases caused by cVDPV2 since 2016 now exceed 2,500. Earlier analyses explored the implications of using different vaccine formulations to respond to cVDPV2 outbreaks and demonstrated how different properties of novel OPV2 (nOPV2) might affect its performance compared to Sabin monovalent OPV2 (mOPV2). These prior analyses used fixed assumptions for how outbreak response would occur, but outbreak response implementation can change. We update an existing global poliovirus transmission model to explore different options for responding with different vaccines and assumptions about scope, delays, immunization intensity, target age groups, and number of rounds. Our findings suggest that in order to successfully stop all cVDPV2 transmission globally, countries and the Global Polio Eradication Initiative need to address the deficiencies in emergency outbreak response policy and implementation. The polio program must urgently act to substantially reduce response time, target larger populations - particularly in high transmission areas - and achieve high coverage with improved access to under-vaccinated subpopulations. Given the limited supplies of nOPV2 at the present, using mOPV2 intensively immediately, followed by nOPV2 intensively if needed and when sufficient quantities become available, substantially increases the probability of ending cVDPV2 transmission globally.

Globally-coordinated cessation of all three serotypes of oral poliovirus vaccine (OPV) represents a critical part of a successful polio endgame, which the Global Polio Eradication Initiative (GPEI) plans to conduct in phases, with serotype 2 OPV cessation completed in mid-2016. Although in 2016 the GPEI expected to globally-coordinate cessation of the remaining OPV serotypes (1 and 3) by 2021, continuing transmission of serotype 1 wild polioviruses to date makes those plans obsolete. With increasing time since the last reported polio case caused by serotype 3 wild poliovirus (in November 2012) leading to high confidence about its successful global eradication, the Global Commission for the Certification of Poliomyelitis Eradication recently certified its eradication. Questions now arise about the optimal timing of serotype 3 OPV (OPV3) cessation. Using an integrated global model that characterizes the risks, costs, and benefits of global polio policy and risk management options, we explored the implications of different options for coordinated cessation of OPV3 prior to COVID-19. Globally-coordinating cessation of OPV3 as soon as possible offers the opportunity to reduce cases of vaccine associated paralytic polio globally. In addition, earlier cessation of OPV3 should reduce the risks of creating serotype 3 circulating vaccine derived polioviruses after OPV3 cessation, which represents a significant threat to the polio endgame given current GPEI plans to reduce preventive OPV supplemental immunization activities starting in 2019.

Introduction Over the last 20 years (2000-2019) the partners of the Global Polio Eradication Initiative (GPEI) invested in the development and application of mathematical models of poliovirus transmission as well as economics, policy, and risk analyses of polio endgame risk management options, including policies related to poliovirus vaccine use during the polio endgame. Areas covered This review provides a historical record of the polio studies published by the three modeling groups that primarily performed the bulk of this work. This review also systematically evaluates the polio transmission and health economic modeling papers published in English in peer-reviewed journals from 2000 to 2019, highlights differences in approaches and methods, shows the geographic coverage of the transmission modeling performed, identified common themes, and discusses instances of similar or conflicting insights or recommendations. Expert opinion Polio modeling performed during the last 20 years substantially impacted polio vaccine choices, immunization policies, and the polio eradication pathway. As the polio endgame continues, national preferences for polio vaccine formulations and immunization strategies will likely continue to change. Future modeling will likely provide important insights about their cost-effectiveness and their relative benefits with respect to controlling polio and potentially achieving and maintaining eradication.

Countries face different poliovirus risks, which imply different benefits associated with continued and future use of oral poliovirus vaccine (OPV) and/or inactivated poliovirus vaccine (IPV). With the Global Polio Eradication Initiative (GPEI) continuing to extend its timeline for ending the transmission of all wild polioviruses and to introduce new poliovirus vaccines, the polio vaccine supply chain continues to expand in complexity. The increased complexity leads to significant uncertainty about supply and costs. Notably, the strategy of phased OPV cessation of all three serotypes to stop all future incidence of poliomyelitis depends on successfully stopping the transmission of all wild polioviruses. Countries also face challenges associated with responding to any outbreaks that occur after OPV cessation, because stopping transmission of such outbreaks requires reintroducing the use of the stopped OPV in most countries. National immunization program leaders will likely consider differences in their risks and willingness‐to‐pay for risk reduction as they evaluate their investments in current and future polio vaccination. Information about the costs and benefits of future poliovirus vaccines, and discussion of the complex situation that currently exists, should prove useful to national, regional, and global decisionmakers and support health economic modeling. Delays in achieving polio eradication combined with increasing costs of poliovirus vaccines continue to increase financial risks for the GPEI.

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.

Beginning in 2013, multiple local government areas (LGAs) in Borno and Yobe in northeast Nigeria and other parts of the Lake Chad basin experienced a violent insurgency that resulted in substantial numbers of isolated and displaced people. Northeast Nigeria represents the last known reservoir country of wild poliovirus (WPV) transmission in Africa, with detection of paralytic cases caused by serotype 1 WPV in 2016 in Borno and serotype 3 WPV in late 2012. Parts of Borno and Yobe are also problematic areas for transmission of serotype 2 circulating vaccine-derived polioviruses, and they continue to face challenges associated with conflict and inadequate health services in security-compromised areas that limit both immunization and surveillance activities. We model poliovirus transmission of all three serotypes for Borno and Yobe using a deterministic differential equation-based model that includes four subpopulations to account for limitations in access to immunization services and dynamic restrictions in population mixing. We find that accessibility issues and insufficient immunization allow for prolonged poliovirus transmission and potential undetected paralytic cases, although as of the end of 2019, including responsive program activities in the modeling suggest die out of indigenous serotypes 1 and 3 WPVs prior to 2020. Specifically, recent and current efforts to access isolated populations and provide oral poliovirus vaccine continue to reduce the risks of sustained and undetected transmission, although some uncertainty remains. Continued improvement in immunization and surveillance in the isolated subpopulations should minimize these risks. Stochastic modeling can build on this analysis to characterize the implications for undetected transmission and confidence about no circulation.

The Global Polio Eradication Initiative (GPEI) partners engaged modelers during the past nearly 20 years to support strategy and policy discussions and decisions, and to provide estimates of the risks, costs, and benefits of different options for managing the polio endgame. Limited efforts to date provided insights related to the validation of the models used for GPEI strategy and policy decisions. However, modeling results only influenced decisions in some cases, with other factors carrying more weight in many key decisions. In addition, the results from multiple modeling groups do not always agree, which supports selection of some strategies and/or policies counter to the recommendations from some modelers but not others. This analysis reflects on our modeling, and summarizes our premises and recommendations, the outcomes of these recommendations, and the implications of key limitations of models with respect to polio endgame strategy. We briefly review the current state of the GPEI given epidemiological experience as of early 2020, which includes failure of the GPEI to deliver on the objectives of its 2013–2018 strategic plan despite full financial support. Looking ahead, we provide context for why the GPEI strategy of global oral poliovirus vaccine (OPV) cessation to end all cases of poliomyelitis looks infeasible given the current state of the GPEI and the failure to successfully stop all transmission of serotype 2 live polioviruses within four years of the April–May 2016 coordinated cessation of serotype 2 OPV use in routine immunization.

Many countries use supplemental immunization activities (SIAs) with oral poliovirus vaccine (OPV) to keep their population immunity to transmission high using preventive, planned SIAs (pSIAs) and outbreaks response SIAs (oSIAs). Prior studies suggested that investment in pSIAs saved substantial health and financial costs due to avoided outbreaks. However, questions remain about the benefits of SIAs, particularly with the recent introduction of inactivated poliovirus vaccine (IPV) into routine immunization in all OPV-using countries. The mounting costs of polio eradication activities and the need to respond to oSIAs threatens the use of limited financial resources for pSIAs, including in the remaining countries with endemic transmission of serotype 1 wild poliovirus (WPV1) (i.e., Pakistan and Afghanistan). A recent updated global poliovirus transmission model suggested that the Global Polio Eradication Initiative (GPEI) is not on track to stop transmission of WPV1 in Pakistan and Afghanistan. We use the updated global model to explore the role of pSIAs to achieve WPV1 eradication. We find that unless Pakistan and Afghanistan manage to increase the quality of bivalent OPV (bOPV) pSIAs, which we model as intensity (i.e., sufficiently high-coverage bOPV pSIAs that reach missed children), the model does not lead to successful eradication of WPV1. Achieving WPV1 eradication, the global objectives of the GPEI, and a successful polio endgame depend on effective and sufficient use of OPV. IPV use plays a negligible role in stopping transmission in Pakistan and Afghanistan and most other countries supported by the GPEI, and more IPV use will not help to stop transmission.

Introduction: The inability to successfully stop all use of oral poliovirus vaccine (OPV) as part of the polio endgame and/or the possibilities of reintroduction of live polioviruses after successful OPV cessation may imply the need to restart OPV production and use, either temporarily or permanently. Areas covered: Complementing prior work that explored the risks of potential OPV restart, we discuss the logistical challenges and implications of restarting OPV in the future, and we develop appropriate assumptions for modeling the possibility of OPV restart. The complexity of phased cessation of the three OPV serotypes implies different potential combinations of OPV use long term. We explore the complexity of polio vaccine choices and key unresolved policy questions that may impact continuing and future use of OPV and/or inactivated poliovirus vaccine (IPV). We then characterize the assumptions required to quantitatively model OPV restart in prospective global-integrated economic policy models for the polio endgame. Expert commentary: Depending on the timing, restarting production of OPV would imply some likely delays associated with ramp-up, re-licensing, and other logistics that would impact the availability and costs of restarting the use of OPV in national immunization programs after globally coordinated cessation of one or more OPV serotypes.

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.

OBJECTIVES: : As efforts to control COVID-19 continue, we simulate hypothetical emergence of wild poliovirus assuming an immunologically naive population. This differs from the current global experience with polio and serves as a model for responding to future pandemics. METHODS: : Applying an established global model, we assume a fully susceptible global population to polioviruses, independently introduce a virus with properties of each of the three stable wild poliovirus serotypes, and explore the impact of strategies that range from doing nothing to seeking global containment and eradication. RESULTS: : We show the dynamics of paralytic cases as the virus spreads globally. We demonstrate the difficulty of eradication unless aggressive efforts begin soon after initial disease detection. Different poliovirus serotypes lead to different trajectories and burdens of disease. In the absence of aggressive measures, the virus would become globally endemic in 2-10 years, and cumulative paralytic cases would exceed 4-40 million depending on serotype, with the burden of disease shifting to younger ages. CONCLUSIONS: : The opportunity to eradicate emerging infections represents an important public policy choice. If the world first observed the emergence of wild poliovirus in 2020, adopting aggressive control strategies would be required to prevent a devastating global pandemic.

Delays in achieving the global eradication of wild poliovirus transmission continue to postpone subsequent cessation of all oral poliovirus vaccine (OPV) use. Countries must stop OPV use to end all cases of poliomyelitis, including vaccine-associated paralytic polio (VAPP) and cases caused by vaccine-derived polioviruses (VDPVs). The Global Polio Eradication Initiative (GPEI) coordinated global cessation of all type 2 OPV (OPV2) use in routine immunization in 2016 but did not successfully end the transmission of type 2 VDPVs (VDPV2s), and consequently continues to use type 2 OPV (OPV2) for outbreak response activities. Using an updated global poliovirus transmission and OPV evolution model, we characterize outbreak response options for 2019-2029 related to responding to VDPV2 outbreaks with a genetically stabilized novel OPV (nOPV2) strain or with the currently licensed monovalent OPV2 (mOPV2). Given uncertainties about the properties of nOPV2, we model different assumptions that appear consistent with the evidence on nOPV2 to date. Using nOPV2 to respond to detected cases may reduce the expected VDPV and VAPP cases and the risk of needing to restart OPV2 use in routine immunization compared to mOPV2 use for outbreak response. The actual properties, availability, and use of nOPV2 will determine its effects on type 2 poliovirus transmission in populations. Even with optimal nOPV2 performance, countries and the GPEI would still likely need to restart OPV2 use in routine immunization in OPV-using countries if operational improvements in outbreak response to stop the transmission of cVDPV2s are not implemented effectively.

COVID‐19 led to a recent high‐profile proposal to reintroduce oral poliovirus vaccine (OPV) in the United States (U.S.), initially in clinical trials, but potentially for widespread and repeated use. We explore logistical challenges related to U.S. OPV administration in 2020, review the literature related to nonspecific effects of OPV to induce innate immunity, and model the health and economic implications of the proposal. The costs of reintroducing a single OPV dose to 331 million Americans would exceed $4.4 billion. Giving a dose of bivalent OPV to the entire U.S. population would lead to an expected 40 identifiable cases of vaccine‐associated paralytic polio, with young Americans at the highest risk. Reintroducing any OPV use in the U.S. poses a risk of restarting transmission of OPV‐related viruses and could lead to new infections in immunocompromised individuals with B‐cell related primary immunodeficiencies that could lead to later cases of paralysis. Due to the lack of a currently licensed OPV in the U.S., the decision to administer OPV to Americans for nonspecific immunological effects would require purchasing limited global OPV supplies that could impact polio eradication efforts. Health economic modeling suggests no role for reintroducing OPV into the U.S. with respect to responding to COVID‐19. Countries that currently use OPV experience fundamentally different risks, costs, and benefits than the U.S. Successful global polio eradication will depend on sufficient OPV supplies, achieving and maintaining high OPV coverage in OPV‐using countries, and effective global OPV cessation and containment in all countries, including the U.S.

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.

Nearly 20 years after the year 2000 target for global wild poliovirus 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 October 2019. We used the model to explore the likely dynamics of poliovirus transmission for 2019–2023, which coincides with a new Global Polio Eradication Initiative (GPEI) 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 based on the 2019–2023 Strategic Plan, the updated model does not show successful eradication of serotype 1 wild poliovirus by 2023 or successful cessation of oral poliovirus vaccine (OPV) serotype 2 related viruses. SOCIAL MEDIA SUMMARY: Risk Analysis modeling shows Global Polio Eradication Initiative not on track to succeed

Silent circulation of polioviruses complicates the polio endgame by affecting the confidence with which we can certify successful eradication (i.e., the end of transmission everywhere) given a long enough period of time with active surveillance and no observed detections. The Global Polio Eradication Initiative continues to use three years without observing paralytic cases caused by wild poliovirus (WPV) infection as an indication of sufficient confidence that poliovirus circulation stopped (assuming good surveillance). Prior modeling demonstrated the complexities of real populations and the imperfect nature of real surveillance systems, and highlighted the need for modeling the specific last reservoirs of undetected circulation. We use a poliovirus transmission model developed for Borno and Yobe to characterize the probability of undetected poliovirus circulation once apparent die-out occurs (i.e., in the absence of epidemiological signals) for WPV serotypes 1 and 3. Specifically, we convert the model to a stochastic form that supports estimates of confidence about no circulation given the time since the last detected event and considering the quality of both immunization and surveillance activities for these states. We find high confidence of no WPV3 circulation, and increasing confidence of WPV1 circulation, which we anticipate will imply high confidence in the absence of any detected cases in mid-2020 so long as Borno and Yobe maintain similar or achieve improved conditions. Our results confirm that gaps in poliovirus surveillance or reaching elimination with borderline sufficient population immunity can substantially increase the time to reach a high confidence about no undetected poliovirus transmission.

Since most poliovirus infections occur with no paralytic symptoms, the possibility of silent circulation complicates the confirmation of the end of poliovirus transmission. Based on empirical field experience and theoretical modeling results, the Global Polio Eradication Initiative identified three years without observing paralytic cases from wild polioviruses with good acute flaccid paralysis surveillance as an indication of sufficient confidence that poliovirus circulation stopped. The complexities of real populations and the imperfect nature of real surveillance systems subsequently demonstrated the importance of specific modeling for areas at high risk of undetected circulation, resulting in varying periods of time required to obtain the same level of confidence about no undetected circulation. Using a poliovirus transmission model that accounts for variability in transmissibility and neurovirulence for different poliovirus serotypes and characterizes country-specific factors (e.g., vaccination and surveillance activities, demographics) related to wild and vaccine-derived poliovirus transmission in Pakistan and Afghanistan, we consider the probability of undetected poliovirus circulation for those countries once apparent die-out occurs (i.e., in the absence of any epidemiological signals). We find that gaps in poliovirus surveillance or reaching elimination with borderline sufficient population immunity could significantly increase the time to reach high confidence about interruption of live poliovirus transmission, such that the path taken to achieve and maintain poliovirus elimination matters. Pakistan and Afghanistan will need to sustain high-quality surveillance for polioviruses after apparent interruption of transmission and recognize that as efforts to identify cases or circulating live polioviruses decrease, the risks of undetected circulation increase and significantly delay the global polio endgame.

Surveillance for poliovirus during the polio endgame remains uncertain. Building on prior modeling of the potential for undetected poliovirus transmission for conditions like those in Pakistan and Afghanistan, we use a hypothetical model to explore several key characteristics of the poliovirus environmental surveillance (ES) system (e.g., number and quality of sites, catchment sizes, and sampling frequency) and characterize their impacts on the time required to reach high (i.e., 95%) confidence about no circulation (CNC95%) following the last detected case of serotype 1 wild poliovirus. The nature and quality of the existing and future acute flaccid paralysis (AFP) surveillance and ES system significantly impact the estimated CNC95% for places like Pakistan and Afghanistan. The analysis illustrates the tradeoffs between number of sites, sampling frequency, and catchments sizes, and suggests diminishing returns of increasing these three factors beyond a point that depends on site quality and the location of sites. Limitations in data quality and the hypothetical nature of the model reduce the ability to assess the extent to which actual ES systems offer benefits that exceed their costs. Thus, although poliovirus ES may help to reduce the time required to reach high confidence about the absence of undetected circulation, the effect strongly depends on the ability to establish effective ES sites in high-risk areas. The costs and benefits of ES require further analysis.

Conditions and evidence continue to evolve related to the prediction of the prevalence of immunodeficiency-associated long-term vaccine-derived poliovirus (iVDPV) excreters, which affect assumptions related to forecasting risks and evaluating potential risk management options. Multiple recent reviews provided information about individual iVDPV excreters, but inconsistencies among the reviews raise some challenges. This analysis revisits the available evidence related to iVDPV excreters and provides updated model estimates that can support future risk management decisions. The results suggest that the prevalence of iVDPV excreters remains highly uncertain and variable, but generally confirms the importance of managing the risks associated with iVDPV excreters throughout the polio endgame in the context of successful cessation of all oral poliovirus vaccine use.

Since most poliovirus infections occur with no paralytic symptoms, the possibility of silent circulation complicates the confirmation of the end of poliovirus transmission. Based on empirical field experience and theoretical modeling results, the Global Polio Eradication Initiative identified three years without observing paralytic cases from wild polioviruses (WPVs) with good acute flaccid paralysis surveillance as an indication of sufficient confidence that poliovirus circulation stopped. The complexities of real populations and the imperfect nature of real surveillance systems subsequently demonstrated the importance of specific modeling for areas at high risk of undetected circulation, resulting in varying periods of time required to obtain the same level of confidence about no undetected circulation. Using a poliovirus transmission model that accounts for variability in transmissibility and neurovirulence for different poliovirus serotypes and characterizes country-specific factors (e.g., vaccination and surveillance activities, demographics) related to wild and vaccine-derived poliovirus transmission in Pakistan and Afghanistan, we consider the probability of undetected poliovirus circulation for those countries once apparent die out occurs (i.e., in the absence of any epidemiological signals). We find that gaps in poliovirus surveillance or reaching elimination with borderline sufficient population immunity could significantly increase the time to reach a high confidence about interruption of live poliovirus transmission, such that the path taken to achieve and maintain poliovirus elimination matters. Pakistan and Afghanistan will need to sustain high-quality surveillance for polioviruses after apparent interruption of transmission and recognize that as efforts to identify cases or circulating live polioviruses decreases, the risks of undetected circulation increase and significantly delay the global polio endgame.

Poliovirus importations into polio-free countries represent a major concern during the final phases of global eradication of wild polioviruses (WPVs). We extend dynamic transmission models to demonstrate the dynamics of population immunity out through 2020 for three countries that only used inactivated poliovirus vaccine (IPV) for routine immunization: the US, Israel, and The Netherlands. For each country, we explore the vulnerability to re-established transmission following an importation for each poliovirus serotype, including the impact of immunization choices following the serotype 1 WPV importation that occurred in 2013 in Israel. As population immunity declines below the threshold required to prevent transmission, countries become at risk for re-established transmission. Although importations represent stochastic events that countries cannot fully control because people cross borders and polioviruses mainly cause asymptomatic infections, countries can ensure that any importations die out. Our results suggest that the general US population will remain above the threshold for transmission through 2020. In contrast, Israel became vulnerable to re-established transmission of importations of live polioviruses by the late 2000s. In Israel, the recent WPV importation and outbreak response use of bivalent oral poliovirus vaccine (bOPV) eliminated the vulnerability to an importation of poliovirus serotypes 1 and 3 for several years, but not serotype 2. The Netherlands experienced a serotype 1 WPV outbreak in 1992–1993 and became vulnerable to re-established transmission in religious communities with low vaccine acceptance around the year 2000, although the general population remains well-protected from widespread transmission. All countries should invest in active management of population immunity to avoid the potential circulation of imported live polioviruses. IPV-using countries may wish to consider prevention opportunities and/or ensure preparedness for response. Countries currently using a sequential IPV/OPV schedule should continue to use all licensed OPV serotypes until global OPV cessation to minimize vulnerability to circulation of imported polioviruses.

With national and global health policymakers facing numerous complex decisions related to achieving and maintaining polio eradication, we expanded our previously developed dynamic poliovirus transmission model using information from an expert literature review process and including additional immunity states and the evolution of oral poliovirus vaccine (OPV). The model explicitly considers serotype differences and distinguishes fecal-oral and oropharyngeal transmission. We evaluated the model by simulating diverse historical experiences with polioviruses, including one country that eliminated wild poliovirus using both OPV and inactivated poliovirus vaccine (IPV) (USA), three importation outbreaks of wild poliovirus (Albania, the Netherlands, Tajikistan), one situation in which no circulating vaccine-derived polioviruses (cVDPVs) emerge despite annual OPV use and cessation (Cuba), three cVDPV outbreaks (Haiti, Madura Island in Indonesia, northern Nigeria), one area of current endemic circulation of all three serotypes (northern Nigeria), and one area with recent endemic circulation and subsequent elimination of multiple serotypes (northern India). We find that when sufficient information about the conditions exists, the model can reproduce the general behavior of poliovirus transmission and outbreaks while maintaining consistency in the generic model inputs. The assumption of spatially homogeneous mixing remains a significant limitation that affects the performance of the differential equation-based model when significant heterogeneities in immunity and mixing may exist. Further studies on OPV virus evolution and improved understanding of the mechanisms of mixing and transmission may help to better characterize poliovirus transmission in populations. Broad application of the model promises to offer insights in the context of global and national policy and economic models.

The Global Polio Laboratory Network maintains active surveillance for circulating live polioviruses by obtaining and testing stool samples from patients with acute flaccid paralysis. However, most poliovirus infections occur with no symptoms, and questions remain about the probability of undetected wild poliovirus (WPV) circulation after the apparent interruption of WPV transmission in different populations. In the context of making decisions about the timing of oral poliovirus vaccine cessation following global eradication of WPV, policy-makers need an understanding of this probability as a function of time. Prior modeling of the probability of undetected circulation relied on relatively simple models and assumptions, which limits extrapolation to current conditions. In this analysis, the authors revisit the topic and highlight important considerations for policy-makers related to the impact of initial conditions and seasonality and emphasize the need to focus on appropriate characterization of conditions in the last likely reservoirs of the virus. The authors conclude that the probability of undetected WPV circulation may vary significantly for different poliovirus serotypes, places, and conditions, which suggests that achieving the same level of confidence about the true interruption of WPV transmission will require different periods of time for different situations.

Background Most poliovirus infections occur with no symptoms and this leads to the possibility of silent circulation, which complicates the confirmation of global goals to permanently end poliovirus transmission. Previous simple models based on hypothetical populations assumed perfect detection of symptomatic cases and suggested the need to observe no paralytic cases from wild polioviruses (WPVs) for approximately 3-4 years to achieve 95% confidence about eradication, but the complexities in real populations and the imperfect nature of surveillance require consideration. Methods We revisit the probability of undetected poliovirus circulation using a more comprehensive model that reflects the conditions in a number of places with different characteristics related to WPV transmission, and we model the actual environmental WPV detection that occurred in Israel in 2013. We consider the analogous potential for undetected transmission of circulating vaccine-derived polioviruses. The model explicitly accounts for the impact of different vaccination activities before and after the last detected case of paralytic polio, different levels of surveillance, variability in transmissibility and neurovirulence among serotypes, and the possibility of asymptomatic participation in transmission by previously-vaccinated or infected individuals. Results We find that prolonged circulation in the absence of cases and thus undetectable by case-based surveillance may occur if vaccination keeps population immunity close to but not over the threshold required for the interruption of transmission, as may occur in northwestern Nigeria for serotype 2 circulating vaccine-derived poliovirus in the event of insufficient tOPV use. Participation of IPV-vaccinated individuals in asymptomatic fecal-oral transmission may also contribute to extended transmission undetectable by case-based surveillance, as occurred in Israel. We also find that gaps or quality issues in surveillance could significantly reduce confidence about actual disruption. Maintaining high population immunity and high-quality surveillance for several years after the last detected polio cases will remain critical elements of the polio end game. Conclusions Countries will need to maintain vigilance in their surveillance for polioviruses and recognize that their risks of undetected circulation may differ as a function of their efforts to manage population immunity and to identify cases or circulating live polioviruses. Electronic supplementary material The online version of this article (doi:10.1186/s12879-015-0791-5) contains supplementary material, which is available to authorized users.

BACKGROUND: After 25 years without poliomyelitis cases caused by circulating wild poliovirus (WPV) in Israel, sewage sampling detected WPV type 1 (WPV1) in April 2013, despite high vaccination coverage with only inactivated poliovirus vaccine (IPV) since 2005. METHODS: We used a differential equation-based model to simulate the dynamics of poliovirus transmission and population immunity in Israel due to past exposure to WPV and use of oral poliovirus vaccine (OPV) in addition to IPV. We explored the influences of various immunization options to stop imported WPV1 circulation in Israel. RESULTS: We successfully modeled the potential for WPVs to circulate without detected cases in Israel. Maintaining a sequential IPV/OPV schedule instead of switching to an IPV-only schedule in 2005 would have kept population immunity high enough in Israel to prevent WPV1 circulation. The Israeli response to WPV1 detection prevented paralytic cases; a more rapid response might have interrupted transmission more quickly. CONCLUSIONS: IPV-based protection alone might not provide sufficient population immunity to prevent poliovirus transmission after an importation. As countries transition to IPV in immunization schedules, they may need to actively manage population immunity and consider continued use of OPV, to avoid the potential circulation of imported live polioviruses before globally coordinated cessation of OPV use.

Nigeria continues to struggle in its efforts to eliminate circulating live polioviruses using oral poliovirus vaccine (OPV).We modeled population immunity, and we estimated cases and the timing of transmission die-out for numerous policies that could accelerate the elimination of wild poliovirus type 1 (WPV1) and help Nigeria manage the risks of circulating vaccine-derived polioviruses (cVDPVs). We used a differential-equation based poliovirus transmission and OPV evolution model focused on northwest Nigeria to characterize the impact and trade-offs of potential vaccination strategies, including the introduction of inactivated poliovirus vaccine (IPV).Northwest Nigeria appears close to reaching the threshold of population immunity it must exceed to stop WPV1 transmission if it continues immunizing previously under-vaccinated children. Avoiding type 2 cVDPVs (cVDPV2s) will depend on using sufficient amounts of trivalent OPV, which will also reduce the risks of cVDPV2s after coordinated cessation of type 2-containing OPV (OPV2). Using IPV during the OPV cessation period may increase population immunity, but it leads to a much lower impact on cVDPV risks than ensuring sufficient trivalent OPV use prior to OPV2 cessation.Northwest Nigeria needs to intensify and sustain its immunization efforts to achieve and maintain higher levels of population immunity.

With national and global health policymakers facing numerous complex decisions related to achieving and maintaining polio eradication, we expanded our previously developed dynamic poliovirus transmission model using information from an expert literature review process and including additional immunity states and the evolution of oral poliovirus vaccine (OPV). The model explicitly considers serotype differences and distinguishes fecal-oral and oropharyngeal transmission. We evaluated the model by simulating diverse historical experiences with polioviruses, including one country that eliminated wild poliovirus using both OPV and inactivated poliovirus vaccine (IPV) (USA), three importation outbreaks of wild poliovirus (Albania, the Netherlands, Tajikistan), one situation in which no circulating vaccine-derived polioviruses (cVDPVs) emerge despite annual OPV use and cessation (Cuba), three cVDPV outbreaks (Haiti, Madura Island in Indonesia, northern Nigeria), one area of current endemic circulation of all three serotypes (northern Nigeria), and one area with recent endemic circulation and subsequent elimination of multiple serotypes (northern India). We find that when sufficient information about the conditions exists, the model can reproduce the general behavior of poliovirus transmission and outbreaks while maintaining consistency in the generic model inputs. The assumption of spatially homogeneous mixing remains a significant limitation that affects the performance of the differential equation-based model when significant heterogeneities in immunity and mixing may exist. Further studies on OPV virus evolution and improved understanding of the mechanisms of mixing and transmission may help to better characterize poliovirus transmission in populations. Broad application of the model promises to offer insights in the context of global and national policy and economic models.

Background Global efforts to eradicate wild polioviruses (WPVs) continue to face challenges due to uninterrupted endemic WPV transmission in three countries and importation-related outbreaks into previously polio-free countries. We explore the potential role of including older children and adults in supplemental immunization activities (SIAs) to more rapidly increase population immunity and prevent or stop transmission. Methods We use a differential equation-based dynamic poliovirus transmission model to analyze the epidemiological impact and vaccine resource implications of expanding target age groups in SIAs. We explore the use of older age groups in SIAs for three situations: alternative responses to the 2010 outbreak in Tajikistan, retrospective examination of elimination in two high-risk states in northern India, and prospective and retrospective strategies to accelerate elimination in endemic northwestern Nigeria. Our model recognizes the ability of individuals with waned mucosal immunity (i.e., immunity from a historical live poliovirus infection) to become re-infected and contribute to transmission to a limited extent. Results SIAs involving expanded age groups reduce overall caseloads, decrease transmission, and generally lead to a small reduction in the time to achieve WPV elimination. Analysis of preventive expanded age group SIAs in Tajikistan or prior to type-specific surges in incidence in high-risk areas of India and Nigeria showed the greatest potential benefits of expanded age groups. Analysis of expanded age group SIAs in outbreak situations or to accelerate the interruption of endemic transmission showed relatively less benefit, largely due to the circulation of WPV reaching individuals sooner or more effectively than the SIAs. The India and Nigeria results depend strongly on how well SIAs involving expanded age groups reach relatively isolated subpopulations that sustain clusters of susceptible children, which we assume play a key role in persistent endemic WPV transmission in these areas. Conclusions This study suggests the need to carefully consider the epidemiological situation in the context of decisions to use expanded age group SIAs. Subpopulations of susceptible individuals may independently sustain transmission, which will reduce the overall benefits associated with using expanded age group SIAs to increase population immunity to a sufficiently high level to stop transmission and reduce the incidence of paralytic cases.