Assessing the stability of polio eradication after the withdrawal of oral polio vaccine

Abstract

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 Type 2 OPV (OPV2) was withdrawn from routine immunization (RI) in April 2016, but ongoing type 2 cVDPV have necessitated the use of OPV2 in outbreak response.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 1/55 . CC-BY-ND 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/084012 doi: bioRxiv preprint first posted online Oct. 27, 2016; 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 SummaryOral 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 commu...

The early evolution of oral poliovirus vaccine is shaped by strong positive selection and tight transmission bottlenecks

“…We identified 111 samples with > 200x coverage ( Figure 1C, red points), 81 samples with > 500x coverage, and 48 samples with > 1000x coverage across the genome, based on averages across a 50-bp sliding window. The majority of samples that yielded at least partial OPV2 genome coverage were collected in the first two months following mOPV2 vaccination ( Figure 1C), which is consistent with the known shedding duration of Sabin type 2 poliovirus infections (34). Most individuals were represented by only one sample, although a subset of individuals had multiple longitudinal samples with at least partial genome data ( Supplementary Figure 1).…”

“…Transmission later in infections when viral load is low and to more distant community contacts was uncommon in this highly immune population (29). Furthermore, bottlenecks may be larger in populations with lower background immunity and higher fecal-oral exposure where naturally acquired doses are likely higher (34), which would allow positive selection among minor variants to act.…”

“…Rather than antigenic escape, we suggest that these mutations lead to improved within-host replication, and therefore greater shedding and transmission. Epidemiologic data suggest that at some unknown point in cVDPV evolution, OPV achieves a level of transmissibility that is similar to that of wild polioviruses (2,34,50). Selection for phenotypes related to this increase in transmissibility, like enteric replication and shedding, are likely the earliest pressures the virus faces (51).…”

Epidemiology of the silent polio outbreak in Rahat, Israel, based on modeling of environmental surveillance data

“…The model parameter estimates are largely reasonable, although the estimated mean infectious period of 11 d (corresponding to γ = 0.09) is lower than values reported in the literature, even if much of the population has received IPV (41). This A B estimate may be a consequence of variable shedding intensity over time, as viral concentrations in stool drop off after the first week of infection (41,42). Since infectious individuals are measured through their shedding into the sewage, a drop in shedding intensity will be interpreted by the model as a shorter duration of infection; i.e., individuals shedding low levels of the virus will be treated as recovered, even if they still harbor the infection.…”

Identification of genes and pathways in human antigen‐presenting cell subsets in response to polio vaccine by bioinformatical analysis

“…Polio vaccinations are based on live‐attenuated or inactivated pathogens. The oral poliovirus vaccine (OPV) contains the live‐attenuated poliovirus that induces immunity but can paralyze vaccinated recipients and generate an outbreak of vaccine‐derived poliovirus . The OPV replicates and activates the adaptive immune system by antigen‐presenting cells (APCs), which migrate to lymphoid organs to present the antigen to T and B cells .…”