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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