AbstractThis introduction for the third special issue on modeling poliovirus risks provides context for the current status of global polio eradication efforts and gives an overview of the individual papers included in the issue. Although risk analysis continues to support the Global Polio Eradication Initiative (GPEI), efforts to finish the job remained off track at the beginning of 2020 and prior to the COVID‐19 pandemic, as discussed in the special issue. The disruptions associated with COVID‐19 occurring now will inevitably change the polio eradication trajectory, and future studies will need to characterize the impacts of these disruptions on the polio endgame.
The devastation caused by periodic measles outbreaks motivated efforts over more than a century to mathematically model measles disease and transmission. Following the identification of rubella, which similarly presents with fever and rash and causes congenital rubella syndrome (CRS) in infants born to women first infected with rubella early in pregnancy, modelers also began to characterize rubella disease and transmission. Despite the relatively large literature, no comprehensive review to date provides an overview of dynamic transmission models for measles and rubella developed to support risk and policy analysis. This systematic review of the literature identifies quantitative measles and/or rubella dynamic transmission models and characterizes key insights relevant for prospective modeling efforts. Overall, measles and rubella represent some of the relatively simplest viruses to model due to their ability to impact only humans and the apparent life‐long immunity that follows survival of infection and/or protection by vaccination, although complexities arise due to maternal antibodies and heterogeneity in mixing and some models considered potential waning immunity and reinfection. This review finds significant underreporting of measles and rubella infections and widespread recognition of the importance of achieving and maintaining high population immunity to stop and prevent measles and rubella transmission. The significantly lower transmissibility of rubella compared to measles implies that all countries could eliminate rubella and CRS by using combination of measles‐ and rubella‐containing vaccines (MRCVs) as they strive to meet regional measles elimination goals, which leads to the recommendation of changing the formulation of national measles‐containing vaccines from measles only to MRCV as the standard of care.
This introduction to the special issue on modeling poliovirus risks provides context about historical efforts to manage polioviruses and reviews the insights from models developed to support risk management and policy development. Following an overview of the contents of the special issue, the introduction explores the road ahead and offers perspective on the legacy of polio eradication.
In the past decade, the use of probabilistic risk analysis techniques to quantitatively address variability and uncertainty in risks increased in popularity as recommended by the 1994 National Research Council that wrote Science and Judgment in Risk Assessment. Under the 1996 Food Quality Protection Act, for example, the U.S. EPA supported the development of tools that produce distributions of risk demonstrating the variability and/or uncertainty in the results. This paradigm shift away from the use of point estimates creates new challenges for risk managers, who now struggle with decisions about how to use distributions in decision making. The challenges for risk communication, however, have only been minimally explored. This presentation uses the case studies of variability in the risks of dying on the ground from a crashing airplane and from the deployment of motor vehicle airbags to demonstrate how better characterization of variability and uncertainty in the risk assessment lead to better risk communication. Analogies to food safety and environmental risks are also discussed. This presentation demonstrates that probabilistic risk assessment has an impact on both risk management and risk communication, and highlights remaining research issues associated with using improved sensitivity and uncertainty analyses in risk assessment.
AbstractDespite 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.
AbstractThe 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.
AbstractGlobally 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.
AbstractCountries 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.
AbstractSilent 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.
AbstractThe 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.
AbstractMany 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.
This article presents a process for an integrated policy analysis that combines risk assessment and benefit‐cost analysis. This concept, which explicitly combines the two types of related analyses, seems to contradict the long‐accepted risk analysis paradigm of separating risk assessment and risk management since benefit‐cost analysis is generally considered to be a part of risk management. Yet that separation has become a problem because benefit‐cost analysis uses risk assessment results as a starting point and considerable debate over the last several years focused on the incompatibility of the use of upper bounds or "safe" point estimates in many risk assessments with benefit‐cost analysis. The problem with these risk assessments is that they ignore probabilistic information. As advanced probabilistic techniques for risk assessment emerge and economic analysts receive distributions of risks instead of point estimates, the artificial separation between risk analysts and the economic/decision analysts complicates the overall analysis. In addition, recent developments in countervailing risk theory suggest that combining the risk and benefit‐cost analyses is required to fully understand the complexity of choices and tradeoffs faced by the decisionmaker. This article also argues that the separation of analysis and management is important, but that benefit‐cost analysis has been wrongly classified into the risk management category and that the analytical effort associated with understanding the economic impacts of risk reduction actions need to be part of a broader risk assessment process.
