The risks, costs, and benefits of possible future global policies for managing polioviruses.

Kids Risk Project, Harvard School of Public Health, 677 Huntington Ave, Third Floor, Boston, MA 02115, USA.
American Journal of Public Health (Impact Factor: 4.23). 08/2008; 98(7):1322-30. DOI: 10.2105/AJPH.2007.122192
Source: PubMed

ABSTRACT We assessed the costs, risks, and benefits of possible future major policy decisions on vaccination, surveillance, response plans, and containment following global eradication of wild polioviruses.
We developed a decision analytic model to estimate the incremental cost-effectiveness ratios and net benefits of risk management options for polio for the 20-year period and stratified the world according to income level to capture important variability between nations.
For low-, lower-middle-, and upper-middle-income groups currently using oral poliovirus vaccine (OPV), we found that after successful eradication of wild polioviruses, OPV cessation would save both costs and lives when compared with continued use of OPV without supplemental immunization activities. We found cost-effectiveness ratios for switching from OPV to inactivated poliovirus vaccine to be higher (i.e., less desirable) than other health investment opportunities, depending on the actual inactivated poliovirus vaccine costs and assumptions about whether supplemental immunization activities with OPV would continue.
Eradication promises billions of dollars of net benefits, although global health policy leaders face difficult choices about future policies. Until successful eradication and coordination of posteradication policies, health authorities should continue routine polio vaccination and supplemental immunization activities.

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    ABSTRACT: Inactivated polio vaccines, which have been used in many countries for more than 50 years, are produced by treatment of live poliovirus (PV) with formaldehyde. However, the molecular mechanisms underlying virus inactivation are not well understood. Infection by PV is initiated by virus binding to specific cell receptors which results in viral particles undergoing sequential conformational changes that generate altered structural forms (135S and 80S particles) and leads to virus cell entry. We have analysed the ability of inactivated PV to bind to the human poliovirus receptor (hPVR) using various techniques such as ultracentrifugation, fluorescent-activated cell sorting (FACS) flow cytometry and real-time RT-PCR. The results showed that although retaining the ability to bind to hPVR, inactivated PV bound less efficiently in comparison to live PV. We also found that inactivated PV showed resistance to structural conversion in vitro as judged by measuring changes in antigenicity, ability to bind to hPVR and viral RNA release at high temperature. Furthermore, viral RNA from inactivated PV was shown to be modified, as cDNA yields obtained by RT-PCR amplification were severely reduced and no infectious virus was recovered after RNA transfection into susceptible cells.
    Journal of Virology 08/2014; 88(20). DOI:10.1128/JVI.01809-14 · 4.65 Impact Factor
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    ABSTRACT: 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.aEuro integral 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.aEuro integral 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.aEuro integral OPV cessation can successfully eliminate all circulating live polioviruses in a population. The polio end game requires active risk management.
    The Journal of Infectious Diseases 11/2014; 210 Suppl 1:S475-84. DOI:10.1093/infdis/jit845 · 5.78 Impact Factor
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    ABSTRACT: Background. The Global Polio Eradication Initiative plans to stop all oral poliovirus vaccine (OPV) after wild poliovirus eradication, starting with serotype 2. Stakeholders continue to discuss the role of using inactivated poliovirus vaccine (IPV) to manage the risks of circulating vaccine-derived polioviruses (cVDPVs) during the end game. Methods.aEuro integral We use a poliovirus transmission and OPV evolution model to explore the impact of various routine immunization policies involving IPV on population immunity dynamics and the probability and magnitude of cVDPV emergences following OPV cessation. Results.aEuro integral Adding a single IPV dose to an OPV-only routine immunization schedule at or just before OPV cessation produces very limited impact on the probability of cVDPV emergences and the number of expected polio cases in settings in which we expect cVDPVs in the absence of IPV use. The highest-cost option of switching to a 3-dose IPV schedule only marginally decreases cVDPV risks. Discontinuing supplemental immunization activities while introducing IPV prior to OPV cessation leads to an increase in cVDPV risks. Conclusions.aEuro integral Introducing a dose of IPV in countries currently using OPV only for routine immunization offers protection from paralysis to successfully vaccinated recipients, but it does little to protect high-risk populations from cVDPV risks.
    The Journal of Infectious Diseases 11/2014; 210 Suppl 1:S485-97. DOI:10.1093/infdis/jit838 · 5.78 Impact Factor

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