Oral Poliovirus Vaccine Evolution and Insights Relevant to Modeling the Risks of Circulating Vaccine‐Derived Polioviruses (cVDPVs)

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.     

The Costs of Future Polio Risk Management Policies

Decisionmakers need information about the anticipated future costs of maintaining polio eradication as a function of the policy options under consideration. Given the large portfolio of options, we reviewed and synthesized the existing cost data relevant to current policies to provide context for future policies. We model the expected future costs of different strategies for continued vaccination, surveillance, and other costs that require significant potential resource commitments. We estimate the costs of different potential policy portfolios for low-, middle-, and high-income countries to demonstrate the variability in these costs. We estimate that a global transition from routine immunization with oral poliovirus vaccine (OPV) to inactivated poliovirus vaccine (IPV) would increase the costs of managing polio globally, although routine IPV use remains less costly than routine OPV use with supplemental immunization activities. The costs of surveillance and a stockpile, while small compared to routine vaccination costs, represent important expenditures to ensure adequate response to potential outbreaks. The uncertainty and sensitivity analyses highlight important uncertainty in the aggregated costs and demonstrates that the discount rate and uncertainty in price and administration cost of IPV drives the expected incremental cost of routine IPV vs. OPV immunization.     

Risk Management in a Polio-Free World

Inherent in the decision to launch the Global Polio Eradication Initiative in 1988 was the expectation for many people that immunization against poliomyelitis would eventually simply stop, as had been the case with smallpox following its eradication in 1977. However, the strategies for managing the risks associated with a "polio-free" world must be continuously refined to reflect new developments, particularly in our understanding of the live polioviruses in the oral poliovirus vaccine (OPV) and in the international approach to managing potential biohazards. The most important of these developments has been the confirmation in 2000 that vaccine-derived polioviruses (VDPVs) can circulate and cause polio outbreaks, making the use of OPV after interruption of wild poliovirus transmission incompatible with a polio-free world. A comprehensive strategy has been developed to minimize the risks associated with eventual OPV cessation, centered on appropriate long-term biocontainment of poliovirus stocks (whether for vaccine production, diagnosis, or research), the controlled reintroduction of any live poliovirus vaccine (i.e., from an OPV stockpile), and appropriate use of the inactivated poliovirus vaccine (IPV). Although some aspects of this risk management strategy are still debated, there is wide agreement that no strategy would entirely eliminate the potential risks to a polio-free world. The current strategy for risk management in a polio-free world will continue to evolve with better characterization of these risks and the development of more effective approaches both to reduce those risks and to limit their consequences should they occur.     

Expert Review on Poliovirus Immunity and Transmission

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.     

Modeling Poliovirus Transmission in Pakistan and Afghanistan to Inform Vaccination Strategies in Undervaccinated Subpopulations

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.     

Modeling Population Immunity to Support Efforts to End the Transmission of Live Polioviruses

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.     

Evaluation of Proactive and Reactive Strategies for Polio Eradication Activities in Pakistan and Afghanistan

Only Pakistan and Afghanistan reported any polio cases caused by serotype 1 wild polioviruses (WPV1s) in 2017. With the dwindling cases in both countries and pressure to finish eradication with the least possible resources, a danger exists of inappropriate prioritization of efforts between the two countries and insufficient investment in the two countries to finish the job. We used an existing differential‐equation‐based poliovirus transmission and oral poliovirus (OPV) evolution model to simulate a proactive strategy to stop transmission, and different hypothetical reactive strategies that adapt the quality of supplemental immunization activities (SIAs) in response to observed polio cases in Pakistan and Afghanistan. To account for the delay in perception and adaptation, we related the coverage of the SIAs in high‐risk, undervaccinated subpopulations to the perceived (i.e., smoothed) polio incidence. Continuation of the current frequency and quality of SIAs remains insufficient to eradicate WPV1 in Pakistan and Afghanistan. Proactive strategies that significantly improve and sustain SIA quality lead to WPV1 eradication and the prevention of circulating vaccine‐derived poliovirus (cVDPV) outbreaks. Reactive vaccination efforts that adapt moderately quickly and independently to changes in polio incidence in each country may succeed in WPV1 interruption after several cycles of outbreaks, or may interrupt WPV1 transmission in one country but subsequently import WPV1 from the other country or enable the emergence of cVDPV outbreaks. Reactive vaccination efforts that adapt independently and either more rapidly or more slowly to changes in polio incidence in each country may similarly fail to interrupt WPV1 transmission and result in oscillations of the incidence. Reactive strategies that divert resources to the country of highest priority may lead to alternating large outbreaks. Achieving WPV1 eradication and subsequent successful OPV cessation in Pakistan and Afghanistan requires proactive and sustained efforts to improve vaccination intensity in under‐vaccinated subpopulations while maintaining high population immunity elsewhere.     

Retrospective Cost-Effectiveness Analyses for Polio Vaccination in the United States

The history of polio vaccination in the United States spans 50 years and includes different phases of the disease, multiple vaccines, and a sustained significant commitment of resources. We estimated cost-effectiveness ratios and assessed the net benefits of polio vaccination applicable at various points in time from the societal perspective and we discounted these back to appropriate points in time. We reconstructed vaccine price data from available sources and used these to retrospectively estimate the total costs of the U.S. historical polio vaccination strategies (all costs reported in year 2002 dollars). We estimate that the United States invested approximately US dollars 35 billion (1955 net present value, discount rate of 3%) in polio vaccines between 1955 and 2005 and will invest approximately US dollars 1.4 billion (1955 net present value, or US dollars 6.3 billion in 2006 net present value) between 2006 and 2015 assuming a policy of continued use of inactivated poliovirus vaccine (IPV) for routine vaccination. The historical and future investments translate into over 1.7 billion vaccinations that prevent approximately 1.1 million cases of paralytic polio and over 160,000 deaths (1955 net present values of approximately 480,000 cases and 73,000 deaths). Due to treatment cost savings, the investment implies net benefits of approximately US dollars 180 billion (1955 net present value), even without incorporating the intangible costs of suffering and death and of averted fear. Retrospectively, the U.S. investment in polio vaccination represents a highly valuable, cost-saving public health program. Observed changes in the cost-effectiveness ratio estimates over time suggest the need for living economic models for interventions that appropriately change with time. This article also demonstrates that estimates of cost-effectiveness ratios at any single time point may fail to adequately consider the context of the investment made to date and the importance of population and other dynamics, and shows the importance of dynamic modeling.     

Understanding Public Perceptions of Benefits and Risks of Childhood Vaccinations in the United States

In the face of a growing public health concern accompanying the reemerging threat of preventable diseases, this research seeks mainly to explain variations in the perceived benefits and risks of vaccinations among the general public in the United States. As Mary Douglas and Aaron Wildavsky's grid‐group cultural theory of risk perception claims, the analytical results based upon original data from a nationwide Internet survey of 1,213 American adults conducted in 2010 suggest that individuals’ cultural predispositions contribute to the formation of their perceptions pertaining to vaccine benefits and risks at both societal and individual levels, in conjunction with other factors suggested by previous risk perception literature, such as perceived prevalence of diseases, trust, knowledge level, and demographic characteristics. Those with a strong hierarch orientation tend to envision greater benefits and lesser risks and conceive of a relatively high ratio of benefit to risk when compared to other cultural types. By contrast, those with a strong fatalist tendency are inclined to emphasize risks and downplay benefits while conceiving of a low vaccination benefit‐risk ratio. Situated between hierarchs and fatalists, strong egalitarians are prone to perceive greater benefits, smaller risks, and a more positive benefit‐risk ratio than strong individualists.     

Use of Quality-Adjusted Life Year Weights with Dose-Response Models for Public Health Decisions: A Case Study of the Risks and Benefits of Fish Consumption

Risks associated with toxicants in food are often controlled by exposure reduction. When exposure recommendations are developed for foods with both harmful and beneficial qualities, however, they must balance the associated risks and benefits to maximize public health. Although quantitative methods are commonly used to evaluate health risks, such methods have not been generally applied to evaluating the health benefits associated with environmental exposures. A quantitative method for risk-benefit analysis is presented that allows for consideration of diverse health endpoints that differ in their impact (i.e., duration and severity) using dose-response modeling weighted by quality-adjusted life years saved. To demonstrate the usefulness of this method, the risks and benefits of fish consumption are evaluated using a single health risk and health benefit endpoint. Benefits are defined as the decrease in myocardial infarction mortality resulting from fish consumption, and risks are defined as the increase in neurodevelopmental delay (i.e., talking) resulting from prenatal methylmercury exposure. Fish consumption rates are based on information from Washington State. Using the proposed framework, the net health impact of eating fish is estimated in either a whole population or a population consisting of women of childbearing age and their children. It is demonstrated that across a range of fish methylmercury concentrations (0-1 ppm) and intake levels (0-25 g/day), individuals would have to weight the neurodevelopmental effects 6 times more (in the whole population) or 250 times less (among women of child-bearing age and their children) than the myocardial infarction benefits in order to be ambivalent about whether or not to consume fish. These methods can be generalized to evaluate the merits of other public health and risk management programs that involve trade-offs between risks and benefits.     

Modeling Poliovirus Risks and the Legacy of Polio Eradication

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.     

GM Foods and the Misperception of Risk Perception

Public opposition to genetically modified (GM) food and crops is widely interpreted as the result of the public's misperception of the risks. With scientific assessment pointing to no unique risks from GM crops and foods, a strategy of accurate risk communication from trusted sources has been advocated. This is based on the assumption that the benefits of GM crops and foods are self-evident. Informed by the interpretation of some qualitative interviews with lay people, we use data from the Eurobarometer survey on biotechnology to explore the hypothesis that it is not so much the perception of risks as the absence of benefits that is the basis of the widespread rejection of GM foods and crops by the European public. Some respondents perceive both risks and benefits, and may be trading off these attributes along the lines of a rational choice model. However, for others, one attribute-benefit-appears to dominate their judgments: the lexicographic heuristic. For these respondents, their perception of risk is of limited importance in the formation of attitudes toward GM food and crops. The implication is that the absence of perceived benefits from GM foods and crops calls into question the relevance of risk communication strategies for bringing about change in public opinion.     

Characterizing Poliovirus Transmission and Evolution: Insights from Modeling Experiences with Wild and Vaccine‐Related Polioviruses

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

Risk‐Based Decision Making for Reoccupation of Contaminated Areas Following a Wide‐Area Anthrax Release

This article presents an analysis of postattack response strategies to mitigate the risks of reoccupying contaminated areas following a release of Bacillus anthracis spores (the bacterium responsible for causing anthrax) in an urban setting. The analysis is based on a hypothetical attack scenario in which individuals are exposed to B. anthracis spores during an initial aerosol release and then placed on prophylactic antibiotics that successfully protect them against the initial aerosol exposure. The risk from reoccupying buildings contaminated with spores due to their reaerosolization and inhalation is then evaluated. The response options considered include: decontamination of the buildings, vaccination of individuals reoccupying the buildings, extended evacuation of individuals from the contaminated buildings, and combinations of these options. The study uses a decision tree to estimate the costs and benefits of alternative response strategies across a range of exposure risks. Results for best estimates of model inputs suggest that the most cost‐effective response for high‐risk scenarios (individual chance of infection exceeding 11%) consists of evacuation and building decontamination. For infection risks between 4% and 11%, the preferred option is to evacuate for a short period, vaccinate, and then reoccupy once the vaccine has taken effect. For risks between 0.003% and 4%, the preferred option is to vaccinate only. For risks below 0.003%, none of the mitigation actions have positive expected monetary benefits. A sensitivity analysis indicates that for high‐infection‐likelihood scenarios, vaccination is recommended in the case where decontamination efficacy is less than 99.99%.     

Equity in Social Risk: Some Empirical Observations

In societal risk analysis the equity of the distribution of risks is often an important consideration owing to the special nature of health risks. We empirically validate some assumptions about equity that have been discussed in the decision analytic literature. Our results show that the way fatalities are distributed throughout a society is considered along with the number of fatalities in evaluating alternative policies involving mortality risks. The concepts of ex ante equity and ex post equity are both shown to be important in judgments of fairness. We next present a decision model based on multiattribute preference theory incorporating the number of fatalities, as well as ex ante equity and ex post equity. When ex ante equity and ex post equity are positively weighted in this fair-risk model , options with more equal risk distributions are ranked higher. Next we empirically show that the distribution of benefits has an impact on judgments of fairness. The fair-risk model does not include information on the benefits distribution, so it would apply when benefits are distributed equally or when the decision maker wishes to not include benefits in the model. We briefly discuss how the notion of proportional equity can incorporate benefits into judgments of the fairness of risk distributions. We then include benefits in a more general model in which fair risk-benefit combinations are those that are exchange equitable. A key implication of this envy-free risk–benefit model is that an unequal distribution of risks may be preferred if it is accompanied by a compensatory differential in benefits consistent with peoples' preference tradeoffs between received benefits and assumed risks. Finally, we discuss how perceived deservedness may influence judgments about equity. We conclude with a discussion of the implications of research on alternative notions of equity for policy makers dealing with social risks.     

Preeradication Vaccine Policy Options for Poliovirus Infection and Disease Control

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.     

A Revised Economic Analysis of Restrictions on the Use of Cell Phones While Driving

Evidence that cell phone use while driving increases the risk of being involved in a motor vehicle crash has led policymakers to consider prohibitions on this practice. However, while restrictions would reduce property loss, injuries, and fatalities, consumers would lose the convenience of using these devices while driving. Quantifying the risks and benefits associated with cell phone use while driving is complicated by substantial uncertainty in the estimates of several important inputs, including the extent to which cell phone use increases a driver's risk of being involved in a crash, the amount of time drivers spend using cell phones (and hence their aggregate contribution to crashes, injuries, and fatalities), and the incremental value to users of being able to make calls while driving. Two prominent studies that have investigated cell phone use while driving have concluded that the practice should not be banned. One finds that the benefits of calls made while driving substantially exceed their costs while the other finds that other interventions could reduce motor vehicle injuries and fatalities (measured in terms of quality adjusted life years) at a lower cost. Another issue is that cell phone use imposes increased (involuntary) risks on other roadway users. This article revises the assumptions used in the two previous analyses to make them consistent and updates them using recent data. The result is a best estimate of zero for the net benefit of cell phone use while driving, a finding that differs substantially from the previous study. Our revised cost-effectiveness estimate for cell phone use while driving moves in the other direction, finding that the cost per quality adjusted life year increases modestly compared to the previous estimate. Both estimates are very uncertain.     

What Defines Us as Professionals in the Field of Risk Analysis?

In a recent issue of Risk Analysis, the then‐President of the Society for Risk Analysis (SRA), Pamela Williams, has some interesting reflections about the risk analysis field. She states that the ability and desire to tackle difficult problems using a risk analytical approach is what uniquely defines us as professionals in the field of risk analysis. The point of departure for her discussion is interviews with the plenary speakers of the 2014 SRA Annual Meeting, who addressed two divisive topics: hydraulic fracking and marijuana use. She points to several themes that invite contributions from the field of risk analysis, including: Has the full spectrum of potential risks and benefits been identified and weighted, and what are the risk tradeoffs or countervailing risks? Inspired by Williams's reflections, and by analyzing the issues raised in the interviews, this article seeks to clarify what our field is really providing. A main conclusion of the article is that it is essential to acknowledge that professionals in the field of risk analysis merely support the tackling of such problems, and that their genuine competence—that which distinguishes them from other professionals—lies in the risk analytical approach itself.