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Due to the very low, but nonzero, paralysis risks associated with the use of oral poliovirus vaccine (OPV), eradicating poliomyelitis requires ending all OPV use globally. The Global Polio Eradication Initiative (GPEI) coordinated cessation of Sabin type 2 OPV (OPV2 cessation) in 2016, except for emergency outbreak response. However, as of early 2023, plans for cessation of bivalent OPV (bOPV, containing types 1 and 3 OPV) remain undefined, and OPV2 use for outbreak response continues due to ongoing transmission of type 2 polioviruses and reported type 2 cases. Recent development and use of a genetically stabilized novel type 2 OPV (nOPV2) leads to additional potential vaccine options and increasing complexity in strategies for the polio endgame. Prior applications of integrated global risk, economic, and poliovirus transmission modeling consistent with GPEI strategic plans that preceded OPV2 cessation explored OPV cessation dynamics and the evaluation of options to support globally coordinated risk management efforts. The 2022–2026 GPEI strategic plan highlighted the need for early bOPV cessation planning. We review the published modeling and explore bOPV cessation immunization options as of 2022, assuming that the GPEI partners will not support restart of the use of any OPV type in routine immunization after a globally coordinated cessation of such use. We model the potential consequences of globally coordinating bOPV cessation in 2027, as anticipated in the 2022–2026 GPEI strategic plan. We do not find any options for bOPV cessation likely to succeed without a strategy of bOPV intensification to increase population immunity prior to cessation. [ABSTRACT FROM AUTHOR]

In May 2016, the Global Polio Eradication Initiative (GPEI) coordinated the cessation of all use of type 2 oral poliovirus vaccine (OPV2), except for emergency outbreak response. Since then, paralytic polio cases caused by type 2 vaccine‐derived polioviruses now exceed 3,000 cases reported by 39 countries. In 2022 (as of April 25, 2023), 20 countries reported detection of cases and nine other countries reported environmental surveillance detection, but no reported cases. Recent development of a genetically modified novel type 2 OPV (nOPV2) may help curb the generation of neurovirulent vaccine‐derived strains; its use since 2021 under Emergency Use Listing is limited to outbreak response activities. Prior modeling studies showed that the expected trajectory for global type 2 viruses does not appear headed toward eradication, even with the best possible properties of nOPV2 assuming current outbreak response performance. Continued persistence of type 2 poliovirus transmission exposes the world to the risks of potentially high‐consequence events such as the importation of virus into high‐transmission areas of India or Bangladesh. Building on prior polio endgame modeling and assuming current national and GPEI outbreak response performance, we show no probability of successfully eradicating type 2 polioviruses in the near term regardless of vaccine choice. We also demonstrate the possible worst‐case scenarios could result in rapid expansion of paralytic cases and preclude the goal of permanently ending all cases of poliomyelitis in the foreseeable future. Avoiding such catastrophic scenarios will depend on the development of strategies that raise population immunity to type 2 polioviruses. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: 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. [ABSTRACT FROM AUTHOR]

With the intensifying global efforts to eradicate wild polioviruses, policymakers face complex decisions related to achieving eradication and managing posteradication risks. These decisions and the expanding use of inactivated poliovirus vaccine (IPV) trigger renewed interest in poliovirus immunity, particularly the role of mucosal immunity in the transmission of polioviruses. Sustained high population immunity to poliovirus transmission represents a key prerequisite to eradication, but poliovirus immunity and transmission remain poorly understood despite decades of studies. In April 2010, the U.S. Centers for Disease Control and Prevention convened an international group of experts on poliovirus immunology and virology to review the literature relevant for modeling poliovirus transmission, develop a consensus about related uncertainties, and identify research needs. This article synthesizes the quantitative assessments and research needs identified during the process. Limitations in the evidence from oral poliovirus vaccine (OPV) challenge studies and other relevant data led to differences in expert assessments, indicating the need for additional data, particularly in several priority areas for research: (1) the ability of IPV-induced immunity to prevent or reduce excretion and affect transmission, (2) the impact of waning immunity on the probability and extent of poliovirus excretion, (3) the relationship between the concentration of poliovirus excreted and infectiousness to others in different settings, and (4) the relative role of fecal-oral versus oropharyngeal transmission. This assessment of current knowledge supports the immediate conduct of additional studies to address the gaps. [ABSTRACT FROM AUTHOR]

Successfully managing risks to achieve wild polioviruses (WPVs) eradication and address the complexities of oral poliovirus vaccine (OPV) cessation to stop all cases of paralytic poliomyelitis depends strongly on our collective understanding of poliovirus immunity and transmission. With increased shifting from OPV to inactivated poliovirus vaccine (IPV), numerous risk management choices motivate the need to understand the tradeoffs and uncertainties and to develop models to help inform decisions. The U.S. Centers for Disease Control and Prevention hosted a meeting of international experts in April 2010 to review the available literature relevant to poliovirus immunity and transmission. This expert review evaluates 66 OPV challenge studies and other evidence to support the development of quantitative models of poliovirus transmission and potential outbreaks. This review focuses on characterization of immunity as a function of exposure history in terms of susceptibility to excretion, duration of excretion, and concentration of excreted virus. We also discuss the evidence of waning of host immunity to poliovirus transmission, the relationship between the concentration of poliovirus excreted and infectiousness, the importance of different transmission routes, and the differences in transmissibility between OPV and WPV. We discuss the limitations of the available evidence for use in polio risk models, and conclude that despite the relatively large number of studies on immunity, very limited data exist to directly support quantification of model inputs related to transmission. Given the limitations in the evidence, we identify the need for expert input to derive quantitative model inputs from the existing data. [ABSTRACT FROM AUTHOR]

The live, attenuated oral poliovirus vaccine (OPV) provides a powerful tool for controlling and stopping the transmission of wild polioviruses (WPVs), although the risks of vaccine-associated paralytic polio (VAPP) and circulating vaccine-derived poliovirus (cVDPV) outbreaks exist as long as OPV remains in use. Understanding the dynamics of cVDPV emergence and outbreaks as a function of population immunity and other risk factors may help to improve risk management and the development of strategies to respond to possible outbreaks. We performed a comprehensive review of the literature related to the process of OPV evolution and information available from actual experiences with cVDPV outbreaks. Only a relatively small fraction of poliovirus infections cause symptoms, which makes direct observation of the trajectory of OPV evolution within a population impractical and leads to significant uncertainty. Despite a large global surveillance system, the existing genetic sequence data largely provide information about transmitted virulent polioviruses that caused acute flaccid paralysis, and essentially no data track the changes that occur in OPV sequences as the viruses transmit largely asymptomatically through real populations with suboptimal immunity. We updated estimates of cVDPV risks based on actual experiences and identified the many limitations in the existing data on poliovirus transmission and immunity and OPV virus evolution that complicate modeling. Modelers should explore the space of potential model formulations and inputs consistent with the available evidence and future studies should seek to improve our understanding of the OPV virus evolution process to provide better information for policymakers working to manage cVDPV risks. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

With the circulation of wild poliovirus (WPV) types 1 and 3 continuing more than a decade after the original goal of eradicating all three types of WPVs by 2000, policymakers consider many immunization options as they strive to stop transmission in the remaining endemic and outbreak areas and prevent reintroductions of live polioviruses into nonendemic areas. While polio vaccination choices may appear simple, our analysis of current options shows remarkable complexity. We offer important context for current and future polio vaccine decisions and policy analyses by developing decision trees that clearly identify potential options currently used by countries as they evaluate national polio vaccine choices. Based on a comprehensive review of the literature we (1) identify the current vaccination options that national health leaders consider for polio vaccination, (2) characterize current practices and factors that appear to influence national and international choices, and (3) assess the evidence of vaccine effectiveness considering sources of variability between countries and uncertainties associated with limitations of the data. With low numbers of cases occurring globally, the management of polio risks might seem like a relatively low priority, but stopping live poliovirus circulation requires making proactive and intentional choices to manage population immunity in the remaining endemic areas and to prevent reestablishment in nonendemic areas. Our analysis shows remarkable variability in the current national polio vaccine product choices and schedules, with combination vaccine options containing inactivated poliovirus vaccine and different formulations of oral poliovirus vaccine making choices increasingly difficult for national health leaders. [ABSTRACT FROM AUTHOR]

Eradication of wild poliovirus (WPV) types 1 and 3, prevention and cessation of circulating vaccine-derived polioviruses, and achievement and maintenance of a world free of paralytic polio cases requires active risk management by focusing on population immunity and coordinated cessation of oral poliovirus vaccine (OPV). We suggest the need for a complementary and different conceptual approach to achieve eradication compared to the current case-based approach using surveillance for acute flaccid paralysis (AFP) to identify symptomatic poliovirus infections. Specifically, we describe a modeling approach to characterize overall population immunity to poliovirus transmission. The approach deals with the realities that exposure to live polioviruses (e.g., WPV, OPV) and/or vaccination with inactivated poliovirus vaccine provides protection from paralytic polio (i.e., disease), but does not eliminate the potential for reinfection or asymptomatic participation in poliovirus transmission, which may increase with time because of waning immunity. The AFP surveillance system provides evidence of symptomatic poliovirus infections detected, which indicate immunity gaps after outbreaks occur, and this system represents an appropriate focus for controlling disease outbreaks. We describe a conceptual dynamic model to characterize population immunity to poliovirus transmission that helps identify risks created by immunity gaps before outbreaks occur, which provides an opportunity for national and global policymakers to manage the risk of poliovirus and prevent outbreaks before they occur. We suggest that dynamically modeling risk represents an essential tool as the number of cases approaches zero. [ABSTRACT FROM AUTHOR]

Decision analytic modeling of polio risk management policies after eradication may help inform decisionmakers about the quantitative tradeoffs implied by various options. Given the significant dynamic complexity and uncertainty involving posteradication decisions, this article aims to clarify the structure of a decision analytic model developed to help characterize the risks, costs, and benefits of various options for polio risk management after eradication of wild polioviruses and analyze the implications of different sources of uncertainty. We provide an influence diagram of the model with a description of each component, explore the impact of different assumptions about model inputs, and present probability distributions of model outputs. The results show that choices made about surveillance, response, and containment for different income groups and immunization policies play a major role in the expected final costs and polio cases. While the overall policy implications of the model remain robust to the variations of assumptions and input uncertainty we considered, the analyses suggest the need for policymakers to carefully consider tradeoffs and for further studies to address the most important knowledge gaps. [ABSTRACT FROM AUTHOR]

After the global eradication of wild polioviruses, the risk of paralytic poliomyelitis from polioviruses will still exist and require active management. Possible reintroductions of poliovirus that can spread rapidly in unprotected populations present challenges to policymakers. For example, at least one outbreak will likely occur due to circulation of a neurovirulent vaccine-derived poliovirus after discontinuation of oral poliovirus vaccine and also could possibly result from the escape of poliovirus from a laboratory or vaccine production facility or from an intentional act. In addition, continued vaccination with oral poliovirus vaccines would result in the continued occurrence of vaccine-associated paralytic poliomyelitis. The likelihood and impacts of reintroductions in the form of poliomyelitis outbreaks depend on the policy decisions and on the size and characteristics of the vulnerable population, which change over time. A plan for managing these risks must begin with an attempt to characterize and quantify them as a function of time. This article attempts to comprehensively characterize the risks, synthesize the existing data available for modeling them, and present quantitative risk estimates that can provide a starting point for informing policy decisions. [ABSTRACT FROM AUTHOR]

The success of the Global Polio Eradication Initiative promises to bring large benefits, including sustained improvements in quality of life (i.e., cases of paralytic disease and deaths avoided) and costs saved from cessation of vaccination. Obtaining and maintaining these benefits requires that policymakers manage the transition from the current massive use of oral poliovirus vaccine (OPV) to a world without OPV and free of the risks of potential future reintroductions of live polioviruses. This article describes the analytical journey that began in 2001 with a retrospective case study on polio risk management and led to development of dynamic integrated risk, economic, and decision analysis tools to inform global policies for managing the risks of polio. This analytical journey has provided several key insights and lessons learned that will be useful to future analysts involved in similar complex decision-making processes. [ABSTRACT FROM AUTHOR]

Appropriate response to polio outbreaks represents an important prerequisite for achieving and maintaining global polio eradication. We use an existing dynamic disease transmission model to evaluate the impact of different aspects of immunization campaigns in response to polio outbreaks occurring in previously polio-free areas. This analysis yields several important insights about response strategies. We find that delay in response represents a crucial risk factor for occurrence of large outbreaks and we characterize the tradeoffs associated with delaying the initial response to achieve better population coverage. We also demonstrate that controlling most potential outbreaks will likely require at least three immunization rounds, although the impact of the optimal interval between rounds varies. Finally, long after oral poliovirus vaccine cessation the choice of target age groups during a response represents an important consideration. [ABSTRACT FROM AUTHOR]

The goal of the World Health Organization is to stop routine use of oral poliovirus vaccine shortly after interruption of wild poliovirus transmission. A key component of this goal is to minimize the risk of reintroduction by destruction of polioviruses except in an absolute minimum number of facilities that serve essential functions and implement effective containment. Effective containment begins with a complete facility risk assessment. This article focuses on characterizing the risks of exposure to polioviruses from the essential vaccine production, quality control, and international reference and research facilities that remain. We consider the potential exposure pathways that might lead to a poliovirus reintroduction, including para-occupational exposures and releases to the environment, and review the literature to provide available estimates and a qualitative assessment of containment risks. Minimizing the risk of poliovirus transmission from a poliovirus facility to increasingly susceptible communities is a crucial and ongoing effort requiring understanding and actively managing the potential exposure pathways. [ABSTRACT FROM AUTHOR]

Effective control and eradication of diseases requires reliable information from surveillance activities, including laboratories, which typically incur real financial costs. This article presents data from a survey we conducted to estimate the costs of the Global Polio Laboratory Network (GPLN), which currently supports aggressive global surveillance for acute flaccid paralysis (AFP) to detect circulating polioviruses. The Global Polio Eradication Initiative (GPEI) of the World Health Organization (WHO) provides resources for some of the laboratory network costs, but the total cost of the network remains relatively poorly characterized given the limited documentation of national contributions. We surveyed network laboratories to quantify AFP surveillance support costs and provide data for cost estimates of potential posteradication surveillance policies related to the laboratories. We estimate that the GPLN currently requires millions (US$ 2002) in total support annually, and that half of the support for national and regional reference laboratories comes from external donors through the WHO or bilateral agreements and half from within nations that host those laboratories. The article also presents the framework for considering the value of information from this global surveillance network and suggests that the expected value of surveillance information from the GPLN currently exceeds its costs. We also provided important insights about how the value of information may change after successful eradication of wild polioviruses. [ABSTRACT FROM AUTHOR]