TY - JOUR T1 - Assessing the stability of polio eradication after the withdrawal of oral polio vaccine JF - bioRxiv DO - 10.1101/084012 SP - 084012 AU - Michael Famulare AU - Christian Selinger AU - Kevin A. McCarthy AU - Guillaume Chabot-Couture AU - Philip A. Eckhoff Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/03/16/084012.abstract N2 - A fundamental complexity of polio eradication is that the elimination of wild poliovirus (WPV) alters the risk-benefit profile of using oral polio vaccine (OPV)—as WPV is eliminated, OPV produces an increasing proportion of the paralytic disease burden since, in rare instances, OPV causes paralysis in vaccine recipients and generates circulating vaccine-derived polio outbreaks (cVDPV) in under-immunized populations. Therefore, to secure the success and long-term stability of polio eradication, OPV use should eventually cease. Type 2 OPV (OPV2) was withdrawn from routine immunization (RI) in April 2016, but ongoing type 2 cVDPV have necessitated the use of OPV2 in outbreak response. Thus the world today: RI with OPV2 has stopped, but OPV2 is needed to interrupt outbreaks, and any future use several years hence will take place in a population with an unprecedented lack of type 2 immunity. To better understand the complex risk landscape of OPV cessation, we summarized data spanning 75 years of polio literature detailing how vaccination affects individual susceptibility to infection and viral shedding. We then examined individual immunity in the context of close-contact transmission data from the USA and India to quantify the impacts of vaccination on transmission. Our results demonstrate that in settings with poor sanitation: (1) OPV has been effective in all populations because it blocks transmission locally, (2) cross-immunity against type 2 produced by bivalent types 1 and 3 OPV is insufficient to block OPV2 transmission, (3) boosting from inactivated polio vaccine (IPV) of immunity from prior live poliovirus exposure is only effective for reducing transmission in settings with evidence of significant re-infection, and (4) OPV transmission is limited more by population immunity than attenuation and so the risk of seeding new cVDPV with OPV use will increase substantially a few years after OPV cessation. We conclude with discussion of the implications for policy decisions about IPV and OPV use and vaccine research.Author Summary Oral polio vaccine (OPV) has played an essential role in the elimination of wild poliovirus (WPV), which persists in only three countries. OPV contains transmissible viruses that can spread from person-to-person, limited by immunity in vaccine recipients and their contacts, and community structure. If OPV spread is insufficiently limited, circulating vaccine-derived poliovirus (cVDPV) outbreaks can occur. After OPV is no longer used in routine immunization, as with the cessation of type 2 OPV in 2016, population immunity limiting transmission will decline. A key question is how this affects the potential of OPV to spread within and across communities. To address this, we calculated the roles of immunity, sanitation, and community structure in limiting OPV spread. Our results derive from a detailed review and synthesis of decades of vaccine trial data and community epidemiological studies. Shedding, dose response, and community structure are quantitatively analyzed to systematically explain and model observations of WPV and OPV circulation in low, moderate, and high-transmission settings. We show that within three years of OPV cessation, renewed OPV use will result in propagating OPV transmission and cVDPVs in high-transmission settings, and that this conclusion is compatible with the observed absence of cVDPVs in low-transmission settings that have long since withdrawn OPV.WPVwild poliovirusOPVoral polio vaccinetOPVtrivalent OPVmOPVmonovalent OPVbOPVbivalent type 1 and 3 OPVVAPPvaccine-associated paralytic poliomyelitiscVDPVcirculating vaccine-derived poliovirusRIroutine immunizationIPVinactivated polio vaccineTCID50the tissue culture infectious dose that induces a cytopathic effect in 50% of infected culturesHID50the human infectious dose equivalent TCID50 that infects 50% of orally-exposed and immunologically-naive humansSESsocioeconomic statusGPEIGlobal Polio Eradication Initiative ER -