Comprehensive screening for immunodeficiency-associated vaccine-derived poliovirus: an essential oral poliovirus vaccine cessation risk management strategy

Abstract

SUMMARYIf the world can successfully control all outbreaks of circulating vaccine-derived poliovirus that may occur soon after global oral poliovirus vaccine (OPV) cessation, then immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) from rare and mostly asymptomatic long-term excretors (defined as ⩾6 months of excretion) will become the main source of potential poliovirus outbreaks for as long as iVDPV excretion continues. Using existing models of global iVDPV prevalence and global long-term poliovirus risk management, we explore the implications of uncertainties related to iVDPV risks, including the ability to identify asymptomatic iVDPV excretors to treat with polio antiviral drugs (PAVDs) and the transmissibility of iVDPVs. The expected benefits of expanded screening to identify and treat long-term iVDPV excretors with PAVDs range from US$0.7 to 1.5 billion with the identification of 25–90% of asymptomatic long-term iVDPV excretors, respectively. However, these estimates depend strongly on assumptions about the transmissibility of iVDPVs and model inputs affecting the global iVDPV prevalence. For example, the expected benefits may decrease to as low as US$260 million with the identification of 90% of asymptomatic iVDPV excretors if iVDPVs behave and transmit like partially reverted viruses instead of fully reverted viruses. Comprehensive screening for iVDPVs will reduce uncertainties and maximize the expected benefits of PAVD use.

Polio endgame risks and the possibility of restarting the use of oral poliovirus vaccine

“…In the context of widespread use of OPV or populations with limited fecal-oral transmission that use IPV-only, any introduced live polioviruses, including iVDPVs, typically do not cause widespread transmission [35–37]. However, as population immunity to transmission declines following OPV cessation, any remaining iVPDVs excreted may begin to cause transmission in the surrounding communities [38]. Finally, the risk of (un)intentional releases from vaccine manufacturing sites or laboratories handling poliovirus-containing materials remains a continuing source of potential outbreaks after cessation [39,40].…”

“…The global model yielded estimates of aggregate health and economic outcomes of major immunization policy choices [40] assuming ideal implementation of risk management strategies, including aggressive outbreak response [44] and OPV intensification wherever needed to prevent post-cessation cVDPV outbreaks [26]. Subsequent publications using the global model considered the impact of specific risk management strategies [7,38,45] and the implications of non-synchronous OPV cessation or subsequent unauthorized OPV use [18,46,47]. However, the ideal implementation of risk management strategies prior to OPV2 cessation unfortunately did not occur universally, leading to cVDPV2 outbreaks in countries that either consciously decided not to intensify tOPV use or could not adequately intensify tOPV use due to civil unrest or poor program performance [48–50].…”

“…However, the model suggested that if iVDPV or other live poliovirus reintroductions occurred long after OPV cessation and/or in places with conditions conducive to intense fecal-oral poliovirus transmission, then this would result in uncontrolled outbreaks and a need to restart OPV in most countries that currently use OPV [40]. Despite the ideal implementation of risk management strategies, the model suggested approximately a 5% chance of needing to restart OPV based on 1,000 stochastic iterations and a somewhat arbitrary threshold of 50,000 post-cessation polio cases used as the trigger to restart OPV use globally [38]. Recognition of the possibility of OPV restarts leads to questions about the nature of risks triggering OPV restarts, the kinetics of uncontrolled outbreaks, and strategies for risk management.…”

“…To summarize the epidemiological situation following OPV2 cessation, we reviewed the experience as of April 2018, and we discuss the evidence in the context of our previously published models. To characterize the risks that may trigger OPV restarts overtime, we complement the existing GPEI post-certification strategic plan [53] with a timeline of the principal outbreak risks for each serotype based on existing global model runs [38,40]. In the context of this analysis, we highlight the limitations of the assumptions in the prior modeling with respect to the implementation of risk management strategies and the likely future polio endgame path.…”

“…To examine triggers for an OPV restart, we characterize the distribution of post-cessation polio cases in the global model. Building on the previously characterized 57 stochastic iterations (out of the 1,000 total) that led to OPV restart in the global model [38], we illustrate the kinetics of outbreaks that preceded OPV restarts. We also identify priorities for future global modeling efforts that might explore the impacts of polio endgame strategies starting in 2019.…”