Modeling the prevalence of immunodeficiency-associated long-term vaccine-derived poliovirus excretors and the potential benefits of antiviral drugs

Abstract

BackgroundA 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.MethodsWe 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.ResultsDue 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.ConclusionsEfforts 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 PID patients 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.

Maintenance and Intensification of Bivalent Oral Poliovirus Vaccine Use Prior to its Coordinated Global Cessation

“…These events may occur even with sufficient bOPV SIAs but likely remain epidemiologically inconsequential. We also did not consider the implications of bOPV SIA choices on iVDPV and other long-term risks, considered elsewhere [17,34]. However, we believe that our choice of populations adequately approximates population immunity dynamics in real high-risk settings.…”

“…However, IPV provides the only source of individual immunity to polio (disease) after OPV cessation and over time provides populations with more protection from poliovirus transmission compared to no IPV. Populations in which conditions favor a greater contribution of oropharyngeal transmission of poliovirus compared to fecal-oral transmission (i.e., better hygiene and sanitation and more temperate climates) coincide with settings with higher expected prevalence of long-term iVDPV excretors [17]. In those populations, IPV provides more protection from poliovirus transmission because IPV provides better protection from oropharyngeal excretion compared to fecal excretion [12,18].…”

Cell-Based High-Throughput Screening Assay Identifies 2′,2′-Difluoro-2′-deoxycytidine Gemcitabine as a Potential Antipoliovirus Agent

“…It is presumed that PV antivirals can significantly benefit poliovirus eradication and maintain the polio-free world. 6,7 However, there are no licensed antiviral drugs available to treat chronically infected poliovirus excretors.…”

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

“…the DES model) estimates the global prevalence of long-term iVDPV excretors as a function of time after OPV cessation [26]. It probabilistically simulates relevant monthly events over the lifetime of all global PID patients, including (i) birth, (ii) PID onset, diagnosis, and treatment, (iii) OPV infections, recovery, and VAPP, and (iv) death [26]. To characterize the variability between countries, the DES model adopts the stratification of the world into 710 populations with different basic reproductive numbers ( R 0 values) from an integrated global model of long-term risk management (i.e.…”