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Thompson K.M.,Kid Risk Inc.
Risk Analysis | Year: 2013

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. © 2013 Society for Risk Analysis.

Thompson K.M.,Kid Risk Inc | Duintjer Tebbens R.J.,Kid Risk Inc
BMC Infectious Diseases | Year: 2015

Background: World leaders remain committed to globally-coordinated oral poliovirus vaccine (OPV) cessation following successful eradication of wild polioviruses, but the best timing and strategy for implementation depend on existing and emerging conditions. Methods: Using an existing integrated global poliovirus risk management model, we explore alternatives to the current timing plan of coordinated cessation of each OPV serotype (i.e., OPV1, OPV2, and OPV3 cessation for serotypes 1, 2, and 3, respectively). We assume the current timing plan involves OPV2 cessation in 2016 followed by OPV1 and OPV3 cessation in 2019 and we compare this to alternative timing options, including cessation of all three serotypes in 2018 or 2019, and cessation of both OPV2 and OPV3 in 2017 followed by OPV1 in 2019. Results: If Supplemtal Immunization Activity frequency remains sufficiently high through cessation of the last OPV serotype, then all OPV cessation timing options prevent circulating vaccine-derived poliovirus (cVDPV) outbreaks after OPV cessation of any serotype. The various OPV cessation timing options result in relatively modest differences in expected vaccine-associated paralytic poliomyelitis cases and expected total of approximately 10-13 billion polio vaccine doses used. However, the expected amounts of vaccine of different OPV formulations needed changes dramatically with each OPV cessation timing option. Overall health economic impacts remain limited for timing options that only change the OPV formulation but preserve the currently planned year for cessation of the last OPV serotype and the global introduction of inactivated poliovirus vaccine (IPV) introduction. Earlier cessation of the last OPV serotype or later global IPV introduction yield approximately $1 billion in incremental net benefits due to saved vaccination costs, although the logistics of implementation of OPV cessation remain uncertain and challenging. Conclusions: All countries should maintain the highest possible levels of population immunity to transmission for each poliovirus serotype prior to the coordinated cessation of the OPV serotype to manage cVDPV risks. If OPV2 cessation gets delayed, then global health leaders should consider other OPV cessation timing options. © 2015 Thompson and Duintjer Tebbens.

Thompson K.M.,Kid Risk Inc | Thompson K.M.,University of Central Florida | Tebbens R.J.D.,Kid Risk Inc
Journal of Infectious Diseases | Year: 2014

Background: Oral poliovirus vaccine (OPV) results in an ongoing burden of poliomyelitis due to vaccine-associated paralytic poliomyelitis and circulating vaccine-derived polioviruses (cVDPVs). This motivates globally coordinated OPV cessation after wild poliovirus eradication.Methods: We modeled poliovirus transmission and OPV evolution to characterize the interaction between population immunity, OPV-related virus prevalence, and the emergence of cVDPVs after OPV cessation. We explored strategies to prevent and manage cVDPVs for countries that currently use OPV for immunization and characterized cVDPV emergence risks and OPV use for outbreak response.Results: Continued intense supplemental immunization activities until OPV cessation represent the best strategy to prevent cVDPV emergence after OPV cessation in areas with insufficient routine immunization coverage. Policy makers must actively manage population immunity before OPV cessation to prevent cVDPVs and aggressively respond if prevention fails. Sufficiently aggressive response with OPV to interrupt transmission of the cVDPV outbreak virus will lead to die-out of OPV-related viruses used for response in the outbreak population. Further analyses should consider the risk of exportation to other populations of the outbreak virus and any OPV used for outbreak response.Conclusions: OPV cessation can successfully eliminate all circulating live polioviruses in a population. The polio end game requires active risk management. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. © 2014 Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Thompson K.M.,Kid Risk Inc. | Tebbens R.J.D.,Kid Risk Inc.
Expert Review of Vaccines | Year: 2012

As the Global Polio Eradication Initiative progresses toward the eradication of wild polioviruses, national and global health leaders must still actively consider options for managing poliovirus risks, including risks associated with using oral poliovirus vaccine. Oral poliovirus vaccine continues to represent a highly effective tool, but its use causes noticeable, rare cases of vaccine-associated paralytic polio and with low coverage it can evolve to become circulating vaccine-derived polioviruse that causes outbreaks. National leaders face a wide range of options, but their choices depend in part on global policies. This article explores the current set of global options for poliovirus eradication or control, discusses constraints and prerequisites for their implementation and offers some insights based on dynamic modeling to inform discussions and frame future economic analyses. © 2012 Expert Reviews Ltd.

Duintjer Tebbens R.J.,Kid Risk Inc. | Thompson K.M.,Kid Risk Inc.
BMC Infectious Diseases | Year: 2015

Background: The Global Polio Eradication Initiative plans for coordinated cessation of oral poliovirus vaccine (OPV) use, beginning with serotype 2-containing OPV (i.e., OPV2 cessation) followed by the remaining two OPV serotypes (i.e., OPV13 cessation). The risk of circulating vaccine-derived poliovirus (cVDPV) outbreaks after OPV cessation of any serotype depends on the serotype-specific population immunity to transmission prior to its cessation. Methods: Based on an existing integrated global model of poliovirus risk management policies, we estimate the serotype-specific OPV doses required to manage population immunity for a strategy of intensive supplemental immunization activities (SIAs) shortly before OPV cessation of each serotype. The strategy seeks to prevent any cVDPV outbreaks after OPV cessation, although actual events remain stochastic. Results: Managing the risks of OPV cessation of any serotype depends on achieving sufficient population immunity to transmission to transmission at OPV cessation. This will require that countries with sub-optimal routine immunization coverage and/or conditions that favor poliovirus transmission conduct SIAs with homotypic OPV shortly before its planned coordinated cessation. The model suggests the need to increase trivalent OPV use in SIAs by approximately 40 % or more during the year before OPV2 cessation and to continue bOPV SIAs between the time of OPV2 cessation and OPV13 cessation. Conclusions: Managing the risks of cVDPVs in the polio endgame will require serotype-specific OPV SIAs in some areas prior to OPV cessation and lead to demands for additional doses of the vaccine in the short term that will affect managers and manufacturers. © 2015 Duintjer Tebbens and Thompson.

Thompson K.M.,Kid Risk Inc | Thompson K.M.,University of Central Florida | Odahowski C.L.,Kid Risk Inc
Risk Analysis | Year: 2016

Economic analyses for vaccine-preventable diseases provide important insights about the value of prevention. We reviewed the literature to identify all of the peer-reviewed, published economic analyses of interventions related to measles and rubella immunization options to assess the different types of analyses performed and characterize key insights. We searched PubMed, the Science Citation Index, and references from relevant articles for studies in English and found 67 analyses that reported primary data and quantitative estimates of benefit-cost or cost-effectiveness analyses for measles and/or rubella immunization interventions. We removed studies that we characterized as cost-minimization analyses from this sample because they generally provide insights that focused on more optimal strategies to achieve the same health outcome. The 67 analyses we included demonstrate the large economic benefits associated with preventing measles and rubella infections using vaccines and the benefit of combining measles and rubella antigens into a formulation that saves the costs associated with injecting the vaccines separately. Despite the importance of population immunity and dynamic viral transmission, most of the analyses used static models to estimate cases prevented and characterize benefits, although the use of dynamic models continues to increase. Many of the analyses focused on characterizing the most significant adverse outcomes (e.g., mortality for measles, congenital rubella syndrome for rubella) and/or only direct costs, and the most complete analyses present data from high-income countries. © 2014 Society for Risk Analysis

Thompson K.M.,Kid Risk Inc. | Duintjer Tebbens R.J.,Kid Risk Inc.
BMC Infectious Diseases | Year: 2015

Background: Prior analyses demonstrated the need for some countries and the Global Polio Eradication Initiative (GPEI) to conduct additional supplemental immunization activities (SIAs) with trivalent oral poliovirus vaccine (tOPV) prior to globally-coordinated cessation of all serotype 2-containing OPV (OPV2 cessation) to prevent the creation of serotype 2 circulating vaccine-derived poliovirus (cVDPV2) outbreaks after OPV2 cessation. The GPEI continues to focus on achieving and ensuring interruption of wild poliovirus serotype 1 (WPV1) and making vaccine choices that prioritize bivalent OPV (bOPV) for SIAs, nominally to increase population immunity to serotype 1, despite an aggressive timeline for OPV2 cessation. Methods: We use an existing dynamic poliovirus transmission model of northwest Nigeria and an integrated global model for long-term poliovirus risk management to explore the impact of tOPV vs. bOPV vaccine choices on population immunity and cVDPV2 risks. Results: Using tOPV instead of bOPV for SIAs leads to a minimal decrease in population immunity to transmission of serotypes 1 and 3 polioviruses, but a significantly higher population immunity to transmission of serotype 2 polioviruses. Failure to use tOPV in enough SIAs results in cVDPV2 emergence after OPV2 cessation in both the northwest Nigeria model and the global model. Despite perceptions to the contrary, prioritizing the use of bOPV over tOPV prior to OPV2 cessation does not significantly improve serotype 1 population immunity to transmission. Conclusions: Immunization leaders need to focus on all three poliovirus serotypes to appropriately manage the risks of OPV cessation in the polio endgame. Focusing on population immunity to transmission to interrupt WPV1 transmission and manage pre-OPV cessation risks of cVDPVs, all countries performing poliovirus SIAs should use tOPV up until the time of OPV2 cessation, after which time they should continue to use the OPV vaccine formulation with all remaining serotypes until coordinated global cessation of those serotypes. © 2015 Thompson and Tebbens.

Thompson K.M.,Kid Risk Inc. | Duintjer Tebbens R.J.,Kid Risk Inc.
Expert Review of Vaccines | Year: 2014

Achieving the goal of a world free of poliomyelitis still requires significant effort. Although polio immunization represents a mature area, the polio endgame will require new tools and strategies, particularly as national and global health leaders coordinate the cessation of all three serotypes of oral poliovirus vaccine and increasingly adopt inactivated poliovirus vaccine (IPV). Poliovirus epidemiology and the global options for managing polioviruses continue to evolve, along with our understanding and appreciation of the resources needed and the risks that require management. Based on insights from modeling, we offer some perspective on the current status of plans and opportunities to achieve and maintain a world free of wild polioviruses and to successfully implement oral poliovirus vaccine cessation. IPV costs and potential wastage will represent an important consideration for national policy makers. Innovations may reduce future IPV costs, but the world urgently needs lower-cost IPV options. © Informa UK, Ltd.

Duintjer Tebbens R.J.,Kid Risk Inc. | Pallansch M.A.,Centers for Disease Control and Prevention | Thompson K.M.,Kid Risk Inc.
BMC Infectious Diseases | Year: 2015

Background: A small number of individuals with B-cell-related primary immunodeficiency diseases (PIDs) may exhibit long-term (prolonged or chronic) excretion of immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) following infection with oral poliovirus vaccine (OPV). These individuals pose a risk of live poliovirus reintroduction into the population after global wild poliovirus eradication and subsequent OPV cessation. Treatment with polio antiviral drugs may potentially stop excretion in some of these individuals and thus may reduce the future population risk. Methods: We developed a discrete event simulation model to characterize the global prevalence of long-term iVDPV excretors based on the best available evidence. We explored the impact of different assumptions about the effectiveness of polio antiviral drugs and the fraction of long-term excretors identified and treated. Results: Due to the rarity of long-term iVDPV excretion and limited data on the survival of PID patients in developing countries, uncertainty remains about the current and future prevalence of long-term iVDPV excretors. While the model suggests only approximately 30 current excretors globally and a rapid decrease after OPV cessation, most of these excrete asymptomatically and remain undetected. The possibility that one or more PID patients may continue to excrete iVDPVs for several years after OPV cessation represents a risk for reintroduction of live polioviruses after OPV cessation, particularly for middle-income countries. With the effectiveness of a single polio antiviral drug possibly as low as 40% and no system in place to identify and treat asymptomatic excretors, the impact of passive use of a single polio antiviral drug to treat identified excretors appears limited. Higher drug effectiveness and active efforts to identify long-term excretors will dramatically increase the benefits of polio antiviral drugs. Conclusions: Efforts to develop a second polio antiviral compound to increase polio antiviral effectiveness and/or to maximize the identification and treatment of affected individuals represent important risk management opportunities for the polio endgame. Better data on the survival of PIDpatients in developing countries and more longitudinal data on their exposure to and recovery from OPV infections would improve our understanding of the risks associated with iVDPV excretors and the benefits of further investments in polio antiviral drugs. © 2015 Duintjer Tebbens et al.

Kalkowska D.A.,Kid Risk Inc. | Kalkowska D.A.,Technical University of Delft | Duintjer Tebbens R.J.,Kid Risk Inc. | Thompson K.M.,Kid Risk Inc.
American Journal of Epidemiology | Year: 2012

The Global Polio Laboratory Network maintains active surveillance for circulating live polioviruses by obtaining and testing stool samples from patients with acute flaccid paralysis. However, most poliovirus infections occur with no symptoms, and questions remain about the probability of undetected wild poliovirus (WPV) circulation after the apparent interruption of WPV transmission in different populations. In the context of making decisions about the timing of oral poliovirus vaccine cessation following global eradication of WPV, policy-makers need an understanding of this probability as a function of time. Prior modeling of the probability of undetected circulation relied on relatively simple models and assumptions, which limits extrapolation to current conditions. In this analysis, the authors revisit the topic and highlight important considerations for policy-makers related to the impact of initial conditions and seasonality and emphasize the need to focus on appropriate characterization of conditions in the last likely reservoirs of the virus. The authors conclude that the probability of undetected WPV circulation may vary significantly for different poliovirus serotypes, places, and conditions, which suggests that achieving the same level of confidence about the true interruption of WPV transmission will require different periods of time for different situations. © 2012 The Auther.

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