Contribution of vaccination to improved survival and health: modelling 50 years of the Expanded Programme on Immunization.

BACKGROUND: WHO, as requested by its member states, launched the Expanded Programme on Immunization (EPI) in 1974 to make life-saving vaccines available to all globally. To mark the 50-year anniversary of EPI, we sought to quantify the public health impact of vaccination globally since the programme's inception. METHODS: In this modelling study, we used a suite of mathematical and statistical models to estimate the global and regional public health impact of 50 years of vaccination against 14 pathogens in EPI. For the modelled pathogens, we considered coverage of all routine and supplementary vaccines delivered since 1974 and estimated the mortality and morbidity averted for each age cohort relative to a hypothetical scenario of no historical vaccination. We then used these modelled outcomes to estimate the contribution of vaccination to globally declining infant and child mortality rates over this period. FINDINGS: Since 1974, vaccination has averted 154 million deaths, including 146 million among children younger than 5 years of whom 101 million were infants younger than 1 year. For every death averted, 66 years of full health were gained on average, translating to 10·2 billion years of full health gained. We estimate that vaccination has accounted for 40% of the observed decline in global infant mortality, 52% in the African region. In 2024, a child younger than 10 years is 40% more likely to survive to their next birthday relative to a hypothetical scenario of no historical vaccination. Increased survival probability is observed even well into late adulthood. INTERPRETATION: Since 1974 substantial gains in childhood survival have occurred in every global region. We estimate that EPI has provided the single greatest contribution to improved infant survival over the past 50 years. In the context of strengthening primary health care, our results show that equitable universal access to immunisation remains crucial to sustain health gains and continue to save future lives from preventable infectious mortality. FUNDING: WHO.

Modeling undetected poliovirus circulation following the 2022 outbreak in the United States.

BACKGROUND: New York State (NYS) reported a polio case (June 2022) and outbreak of imported type 2 circulating vaccine-derived poliovirus (cVDPV2) (last positive wastewater detection in February 2023), for which uncertainty remains about potential ongoing undetected transmission. RESEARCH DESIGN AND METHODS: Extending a prior deterministic model, we apply an established stochastic modeling approach to characterize the confidence about no circulation (CNC) of cVDPV2 as a function of time since the last detected signal of transmission (i.e. poliovirus positive acute flaccid myelitis case or wastewater sample). RESULTS: With the surveillance coverage for the NYS population majority and its focus on outbreak counties, modeling suggests a high CNC (95%) within 3-10 months of the last positive surveillance signal, depending on surveillance sensitivity and population mixing patterns. Uncertainty about surveillance sensitivity implies longer durations required to achieve higher CNC. CONCLUSIONS: In populations that maintain high overall immunization coverage with inactivated poliovirus vaccine (IPV), rare polio cases may occur in un(der)-vaccinated individuals. Modeling demonstrates the unlikeliness of type 2 outbreaks reestablishing endemic transmission or resulting in large absolute numbers of paralytic cases. Achieving and maintaining high immunization coverage with IPV remains the most effective measure to prevent outbreaks and shorten the duration of imported poliovirus transmission.

Trade-offs of different poliovirus vaccine options for outbreak response in the United States and other countries that only use inactivated poliovirus vaccine (IPV) in routine immunization.

Delays in achieving polio eradication have led to ongoing risks of poliovirus importations that may cause outbreaks in polio-free countries. Because of the low, but non-zero risk of paralysis with oral poliovirus vaccines (OPVs), countries that achieve and maintain high national routine immunization coverage have increasingly shifted to exclusive use of inactivated poliovirus vaccine (IPV) for all preventive immunizations. However, immunization coverage within countries varies, with under-vaccinated subpopulations potentially able to sustain transmission of imported polioviruses and experience local outbreaks. Due to its cost, ease-of-use, and ability to induce mucosal immunity, using OPV as an outbreak control measure offers a more cost-effective option in countries in which OPV remains in use. However, recent polio outbreaks in IPV-only countries raise questions about whether and when IPV use for outbreak response may fail to stop poliovirus transmission and what consequences may follow from using OPV for outbreak response in these countries. We systematically reviewed the literature to identify modeling studies that explored the use of IPV for outbreak response in IPV-only countries. In addition, applying a model of the 2022 type 2 poliovirus outbreak in New York, we characterized the implications of using different OPV formulations for outbreak response instead of IPV. We also explored the hypothetical scenario of the same outbreak except for type 1 poliovirus instead of type 2. We find that using IPV for outbreak response will likely only stop outbreaks for polioviruses of relatively low transmission potential in countries with very high overall immunization coverage, seasonal transmission dynamics, and only if IPV immunization interventions reach some unvaccinated individuals. Using OPV for outbreak response in IPV-only countries poses substantial risks and challenges that require careful consideration, but may represent an option to consider for some outbreaks in some populations depending on the properties of the available vaccines and coverage attainable.

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 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.

Oral polio vaccine stockpile modeling: insights from recent experience.

BACKGROUND: Achieving polio eradication requires ensuring the delivery of sufficient supplies of the right vaccines to the right places at the right times. Despite large global markets, decades of use, and large quantity purchases of polio vaccines by national immunization programs and the Global Polio Eradication Initiative (GPEI), forecasting demand for the oral poliovirus vaccine (OPV) stockpile remains challenging. RESEARCH DESIGN AND METHODS: We review OPV stockpile experience compared to pre-2016 expectations, actual demand, and changes in GPEI policies related to the procurement and use of type 2 OPV vaccines. We use available population and immunization schedule data to explore polio vaccine market segmentation, and its role in polio vaccine demand forecasting. RESULTS: We find that substantial challenges remain in forecasting polio vaccine needs, mainly due to (1) deviations in implementation of plans that formed the basis for earlier forecasts, (2) lack of alignment of tactics/objectives among GPEI partners and other key stakeholders, (3) financing, and (4) uncertainty about development and licensure timelines for new polio vaccines and their field performance characteristics. CONCLUSIONS: Mismatches between supply and demand over time have led to negative consequences associated with both oversupply and undersupply, as well as excess costs and potentially preventable cases.

Health Economic Analysis of Antiviral Drugs in the Global Polio Eradication Endgame.

BACKGROUND: Polio antiviral drugs (PAVDs) may provide a critical tool in the eradication endgame by stopping poliovirus infections in immunodeficient individuals who may not clear the virus without therapeutic intervention. Although prolonged/chronic poliovirus excreters are rare, they represent a source of poliovirus reintroduction into the general population. Prior studies that assumed the successful cessation of all oral poliovirus vaccine (OPV) use estimated the potential upper bound of the incremental net benefits (INBs) of resource investments in research and development of PAVDs. However, delays in polio eradication, OPV cessation, and the development of PAVDs necessitate an updated economic analysis to reevaluate the costs and benefits of further investments in PAVDs. METHODS: Using a global integrated model of polio transmission, immunity, vaccine dynamics, risks, and economics, we explore the risks of reintroduction of polio transmission due to immunodeficiency-related vaccine-derived poliovirus (iVDPV) excreters and reevaluate the upper bound of the INBs of PAVDs. RESULTS: Under the current conditions, for which the use of OPV will likely continue for the foreseeable future, even with successful eradication of type 1 wild poliovirus by the end of 2023 and continued use of Sabin OPV for outbreak response, we estimate an upper bound INB of 60 million US$2019. With >100 million US$2019 already invested in PAVD development and with the introduction of novel OPVs that are less likely to revert to neurovirulence, our analysis suggests the expected INBs of PAVDs would not offset their costs. CONCLUSIONS: While PAVDs could play an important role in the polio endgame, their expected economic benefits drop with ongoing OPV use and poliovirus transmissions. However, stakeholders may pursue the development of PAVDs as a desired product regardless of their economic benefits.HighlightsWhile polio antiviral drugs could play an important role in the polio endgame, their expected economic benefits continue to drop with delays in polio eradication and the continued use of oral poliovirus vaccines.The incremental net benefits of investments in polio antiviral drug development and screening for immunodeficiency-related circulating polioviruses are small.Limited global resources are better spent on increasing global population immunity to polioviruses to stop and prevent poliovirus transmission.

Complexity of options related to restarting oral poliovirus vaccine (OPV) in national immunization programs after OPV cessation.

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.

Looking back at prospective modeling of outbreak response strategies for managing global type 2 oral poliovirus vaccine (OPV2) cessation.

Introduction: Detection of poliovirus transmission and ongoing oral poliovirus vaccine (OPV) use continue to delay poliomyelitis eradication. In 2016, the Global Polio Eradication Initiative (GPEI) coordinated global cessation of type 2 OPV (OPV2) for preventive immunization and limited its use to emergency outbreak response. In 2019, GPEI partners requested restart of some Sabin OPV2 production and also accelerated the development of a genetically modified novel OPV2 vaccine (nOPV2) that promised greater genetic stability than monovalent Sabin OPV2 (mOPV2). Methods: We reviewed integrated risk, economic, and global poliovirus transmission modeling performed before OPV2 cessation, which recommended multiple risk management strategies to increase the chances of successfully ending all transmission of type 2 live polioviruses. Following OPV2 cessation, strategies implemented by countries and the GPEI deviated from model recommended risk management strategies. Complementing other modeling that explores prospective outbreak response options for improving outcomes for the current polio endgame trajectory, in this study we roll back the clock to 2017 and explore counterfactual trajectories that the polio endgame could have followed if GPEI had: (1) managed risks differently after OPV2 cessation and/or (2) developed nOPV2 before and used it exclusively for outbreak response after OPV2 cessation. Results: The implementation of the 2016 model-based recommended outbreak response strategies could have ended (and could still substantially improve the probability of ending) type 2 poliovirus transmission. Outbreak response performance observed since 2016 would not have been expected to achieve OPV2 cessation with high confidence, even with the availability of nOPV2 prior to the 2016 OPV2 cessation. Discussion: As implemented, the 2016 OPV2 cessation failed to stop type 2 transmission. While nOPV2 offers benefits of lower risk of seeding additional outbreaks, its reduced secondary spread relative to mOPV2 may imply relatively higher coverage needed for nOPV2 than mOPV2 to stop outbreaks.

Outbreak management strategies for cocirculation of multiple poliovirus types.

Prior modeling studies showed that current outbreak management strategies are unlikely to stop outbreaks caused by type 1 wild polioviruses (WPV1) or circulating vaccine-derived polioviruses (cVDPVs) in many areas, and suggested increased risks of outbreaks with cocirculation of more than one type of poliovirus. The surge of type 2 poliovirus transmission that began in 2019 and continues to date, in conjunction with decreases in preventive supplemental immunization activities (SIAs) for poliovirus types 1 and 3, has led to the emergence of several countries with cocirculation of more than one type of poliovirus. Response to these emerging cocirculation events is theoretically straightforward, but the different formulations, types, and inventories of oral poliovirus vaccines (OPVs) available for outbreak response present challenging practical questions. In order to demonstrate the implications of using different vaccine options and outbreak campaign strategies, we applied a transmission model to a hypothetical population with conditions similar to populations currently experiencing outbreaks of cVDPVs of both types 1 and 2. Our results suggest prevention of the largest number of paralytic cases occurs when using (1) trivalent OPV (tOPV) (or coadministering OPV formulations for all three types) until one poliovirus outbreak type dies out, followed by (2) using a type-specific OPV until the remaining poliovirus outbreak type also dies out. Using tOPV first offers a lower overall expected cost, but this option may be limited by the willingness to expose populations to type 2 Sabin OPV strains. For strategies that use type 2 novel OPV (nOPV2) concurrently administered with bivalent OPV (bOPV, containing types 1 and 3 OPV) emerges as a leading option, but questions remain about feasibility, logistics, type-specific take rates, and coadministration costs.

Outbreak response strategies with type 2-containing oral poliovirus vaccines.

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.

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.

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

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

Health economic analysis of vaccine options for the polio eradication endgame: 2022-2036.

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.

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.

Polio health economics: assessing the benefits and costs of polio, non-polio, and integrated activities of the Global Polio Eradication Initiative.

Background: Investments made by countries and donors to support polio eradication and the Global Polio Eradication Initiative (GPEI) over the past 35 years provided financial support for significant health interventions beyond the prevention of polio. Prior economic analyses that sought to quantify the economic benefits of some interventions encountered insufficient data and evidence associated with non-polio-specific activities. The 2022-2026 GPEI Strategic Plan explicitly identified integration and gender equity as funded mandates that must move forward in parallel with polio eradication, but these goals remain vaguely defined from a health economic perspective. Methods: To ensure unambiguous and full accounting for all financial investments in the GPEI, polio eradication, and other desirable objectives, we identify the health economic analysis methods and inputs needed to ensure transparent financial accountability and cost-effective use of funds. Results: Sufficient inputs and methods exist to characterize the health and economic benefits of polio-specific activities, but we identified the need for additional information and method development for some non-polio-specific and cost-sharing activities. Donors who seek to support non-polio-specific objectives as part of the GPEI may want to provide dedicated support financing for which it may be difficult to apply typical health economic criteria and to expect net health and/or net economic benefits. Conclusions: Given the mixture of funding sources provided to the GPEI, which includes support by governments and private donors, we recommend that the GPEI separately account for financial needs that represent necessities for polio eradication from those used for other stated objectives. An added layer of specificity that identifies all funds according to each activity, the accountable party and/or parties, and the associated measurable health or other outcome(s), will enable improved health economic analyses and reporting to donors who seek to track returns on their investments.

Health economic analyses of secondary vaccine effects: a systematic review and policy insights.

INTRODUCTION: Numerous analyses demonstrate substantial health-economic impacts of primary vaccine effects (preventing or mitigating clinical manifestations of the diseases they target), but vaccines may also be associated with secondary effects, previously known as nonspecific, heterologous, or off-target effects. AREAS COVERED: We define key concepts to distinguish primary and secondary vaccine effects for health economic analyses, summarized terminology used in different fields, and perform a systematic review of health economic analyses focused on secondary vaccine effects (SVEs). EXPERT OPINION: Health economists integrate evidence from multiple fields, which often use incomplete or inconsistent definitions. Like regulators and policy makers, health economists require high-quality evidence of specific effects. Consistent with the limited evidence on mechanisms of action for SVEs, the associated health economic literature remains highly limited, with 4 studies identified by our systematic review. The lack of specific and well-controlled evidence that supports quantification of specific SVEs limits the consideration of these effects in vaccine research, development, regulatory, and recommendation decisions and health economic analyses.

Hypothetical emergence of poliovirus in 2020: part 1. Consequences of policy decisions to respond using nonpharmaceutical interventions.

OBJECTIVES: As efforts to control COVID-19 continue, we simulate hypothetical emergence of wild poliovirus assuming an immunologically naïve 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 have been required to prevent a devastating global pandemic.