Modeling Poliovirus Transmission and Responses in New York State.

BACKGROUND: In July 2022, New York State (NYS) reported a case of paralytic polio in an unvaccinated young adult, and subsequent wastewater surveillance confirmed sustained local transmission of type 2 vaccine-derived poliovirus (VDPV2) in NYS with genetic linkage to the paralyzed patient. METHODS: We adapted an established poliovirus transmission and oral poliovirus vaccine evolution model to characterize dynamics of poliovirus transmission in NYS, including consideration of the immunization activities performed as part of the declared state of emergency. RESULTS: Despite sustained transmission of imported VDPV2 in NYS involving potentially thousands of individuals (depending on seasonality, population structure, and mixing assumptions) in 2022, the expected number of additional paralytic cases in years 2023 and beyond is small (less than 0.5). However, continued transmission and/or reintroduction of poliovirus into NYS and other populations remains a possible risk in communities that do not achieve and maintain high immunization coverage. CONCLUSIONS: In countries such as the United States that use only inactivated poliovirus vaccine, even with high average immunization coverage, imported polioviruses may circulate and pose a small but nonzero risk of causing paralysis in nonimmune individuals.

Worst-case scenarios: Modeling uncontrolled type 2 polio transmission.

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.

Coordinated global cessation of oral poliovirus vaccine use: Options and potential consequences.

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.

Modeling undetected live type 1 wild poliovirus circulation after apparent interruption of transmission: Pakistan and Afghanistan.

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.

Modeling scenarios for ending poliovirus transmission in Pakistan and Afghanistan.

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.

Polio by the Numbers-A Global Perspective.

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.

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.

Health and Economic Outcomes Associated with Polio Vaccine Policy Options: 2019-2029.

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 oral poliovirus vaccine (OPV) cessation represents a cost-effective option. The risks and costs of needing to restart 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.

An Updated Economic Analysis of the Global Polio Eradication Initiative.

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 U.S. 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 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.

Reflections on Modeling Poliovirus Transmission and the Polio Eradication Endgame.

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.

Insights From Modeling Preventive Supplemental Immunization Activities as a Strategy to Eliminate Wild Poliovirus Transmission in Pakistan and Afghanistan.

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.

A Health Economic Analysis for Oral Poliovirus Vaccine to Prevent COVID-19 in the United States.

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.

Modeling Undetected Live Poliovirus Circulation After Apparent Interruption of Transmission: Borno and Yobe in Northeast Nigeria.

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.

Potential Future Use, Costs, and Value of Poliovirus Vaccines.

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.

Expected Implications of Globally Coordinated Cessation of Serotype 3 Oral Poliovirus Vaccine (OPV) Before Serotype 1 OPV.

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.

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.

Modeling Poliovirus Transmission in Borno and Yobe, Northeast Nigeria.

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.

Updated Characterization of Outbreak Response Strategies for 2019-2029: Impacts of Using a Novel Type 2 Oral Poliovirus Vaccine Strain.

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.

Environmental Surveillance System Characteristics and Impacts on Confidence About No Undetected Serotype 1 Wild Poliovirus Circulation.

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.