Risks of Paralytic Disease Due to Wild or Vaccine-Derived Poliovirus after Eradication
by Radboud J. Duintjer Tebbens, Mark A. Pallansch, Olen M. Kew, Victor M. Cáceres, Hamid Jafari, Stephen L. Cochi, Roland W. Sutter, R. Bruce Aylward, and Kimberly M. Thompson, Risk Analysis 2006;26(6):1471-1505

Abstract

After the global eradication of wild polioviruses, the risk of paralytic poliomyelitis from polioviruses will still exist and require active management. Possible reintroductions of poliovirus that can spread rapidly in unprotected populations present challenges to policymakers. For example, at least one outbreak will likely occur due to circulation of a neurovirulent vaccine-derived poliovirus after discontinuation of oral poliovirus vaccine and also could possibly result from the escape of poliovirus from a laboratory or vaccine production facility or from an intentional act. In addition, continued vaccination with oral poliovirus vaccines would result in the continued occurrence of vaccine-associated paralytic poliomyelitis. The likelihood and impacts of reintroductions in the form of poliomyelitis outbreaks depend on the policy decisions and on the size and characteristics of the vulnerable population, which change over time. A plan for managing these risks must begin with an attempt to characterize and quantify them as a function of time. This article attempts to comprehensively characterize the risks, synthesize the existing data available for modeling them, and present quantitative risk estimates that can provide a starting point for informing policy decisions.

Answers to frequently asked questions

What are the study’s main findings?
What are the study’s main recommendations?
What do the risks mean for national health leaders?
Background on polio

What are the study’s main findings?

  • By synthesizing the available data, we can characterize the uncertain and variable risks associated with post-eradication polio risk management policies over time. Given our global focus and the large differences that exist between countries, we stratified the risks using World Bank income levels (i.e., we characterize them separately for low-income, lower middle-income, upper middle-income, and high-income countries) assuming that this adequately captures differences between nations at the global level.
  • Low and lower middle-income countries face the highest risks of outbreaks, and high-income countries, which are likely to continue to vaccinate using inactivated poliovirus vaccine (IPV), face the lowest risks.
  • The analysis shows that we should expect at least one post-eradication outbreak globally (defined as at least one paralytic polio case) with a relatively high probability. As stated in the paper: "Combining all of the risk estimates with global population forecasts suggests an approximately 50 to 100% chance of at least one outbreak during the first 20 years after global OPV cessation." This result is not surprising. For smallpox, the only disease successfully eradicated to date, one fatal laboratory-acquired case occurred after eradication. Of course if we fail to eradicate wild polioviruses then polio outbreaks will continue in the future for certain (i.e., with probability=1 or 100%).
  • If routine oral poliovirus vaccine (OPV) use continues after eradication, then circulating vaccine-derived polioviruses (cVDPVs) will most likely lead to continued frequent outbreaks. Uncertainty exists about these risks, which we captured in part using two risk cases: one that quantifies the risks based on confirmed cVDPVs only, and the other that includes both cVDPVs and ambiguous vaccine-derived polioviruses (aVDPVs) (for which the origin and importance of the observed data are more ambiguous, see full paper for details).
  • If routine OPV use stops, the outbreak probabilities are highest in the short term due to cVDPVs, while the low risks from (1) prolonged and chronic immunodeficient VDPV excretors (iVDPVs), (2) poliovirus releases from laboratories or IPV production sites, and (3) intentional poliovirus releases dominate in the long term.
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What are the study’s main recommendations?
  • The possibility of outbreaks after eradication means that policy makers should not assume zero risks and they must prepare to swiftly respond to outbreaks in an OPV-cessation era. As stated in the paper, "the world must prepare for the posteradication transition and commit to sustained eradication and containment, which may require redefining the goal after interruption of wild poliovirus transmission as continued absence of sustained circulation of polioviruses (including VDPVs)."
  • Future efforts to better understand the true prevalence of immunodeficient VDPV excretors (iVDPVs) and the risk of virus spread from these individuals should help to better characterize the long-term risks.
  • High-quality surveillance remains essential to ensure complete interruption of wild polioviruses before OPV cessation. Stochastic models may help determine the optimal time for safely stopping routine OPV use as a function of surveillance quality.
  • Further research is needed to develop adequate outbreak response strategies that minimize the risk of OPV viruses used in outbreak response becoming sources of VDPVs, and to improve our understanding about the risks. This study does not address the possibility of continued undetected wild poliovirus circulation after apparent wild poliovirus eradication, the risk of VDPVs related to outbreak response, or the magnitude of post-eradication outbreaks using a dynamic model, which future studies should further consider.
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What do the risks mean for national leaders?
  • The relatively high probability of at least one global outbreak (defined as at least one paralytic polio case) after eradication of wild polioviruses suggests that all leaders need to prepare, but where and when any such outbreak might occur remains uncertain. National leaders might want to consider the risk estimates in this paper as a starting point for estimating their own national risks, although this analysis used a global focus and relies on stratification at a very high level (i.e., dividing nations into four income-levels and assuming similar risks for countries within those levels). Any single nation's risks will depend on its population, population immunity, and the policy options that it and other countries pursue.
  • For simplicity and consistency, the paper characterizes the annual risks of an outbreak per 100 million (i.e., 100,000,000) people, called the outbreak rate per year. This means that nations can use these estimates as a starting point by adjusting them appropriately for their population sizes. For example, risk estimates for a population of 50 million are half (i.e., 50/100) as large. We suggest caution in assumptions about population sizes over 100 million and note that the risks are not strictly additive, because by definition probabilities cannot exceed 1.
  • You can explore the risks further using pull-down menus (in a new window that will open) for:
    Low-income countries
    Lower middle-income countries
    Upper middle-income countries
    High-income countries
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