On June 22, 2022, the UK Health Security Agency announced that vaccine-derived poliovirus type 2 (VDPV2) had been repeatedly detected in sewage in London, UK.

 Several weeks later, the New York State Department of Health reported a case of acute flaccid paralysis caused by VDPV2 in an unvaccinated individual; the first case of poliomyelitis in almost a decade in the USA.

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 A similar virus has also been detected in sewage from Jerusalem, Israel.

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These events herald an unexpected and concerning development in the fight against polio; they demonstrate that vaccine-derived polioviruses (VDPVs) can emerge in high-income settings with good sanitation where the live oral polio vaccine (OPV) is not in use. Moreover, these incidents indicate that VDPV2 transmission might be more widespread than is currently understood, risking further cases of paralytic disease among undervaccinated individuals. There is limited precedent for responding to VDPV2 transmission in these settings, and thus the impact of all interventions made by the UK and USA must be closely evaluated.

VDPVs are not a new phenomenon. It is well recognised that the live, highly attenuated poliovirus strains (Sabin 1, 2, and 3), which constitute the trivalent OPV can, on occasion, mutate sufficiently to regain virulence and cause outbreaks of poliomyelitis.

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 Although genetic reversion to generate circulating VDPVs (cVDPVs) is infrequent, it occurs more readily in settings of persistently low immunisation coverage, where extensive viral replication and person-to-person transmission are possible.

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 In recent years, there has been a marked increase in cVDPV outbreaks and resultant cases of paralytic poliomyelitis in susceptible individuals. In 2020, there were 1113 cases of poliomyelitis caused by cVDPVs across 27 countries, compared with 140 wild poliovirus type 1 cases limited to Afghanistan and Pakistan; this represented the highest total number of poliomyelitis cases in over a decade.

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 The majority of cVDPV strains have evolved from the Sabin 2 virus, and thus are designated as cVDPV2.

The rise in the number and scale of cVDPV2 outbreaks over the past 4 years is multifactorial. In 2016, there was a synchronised global withdrawal of Sabin 2-containing trivalent OPV, and a switch to bivalent OPV (Sabin 1 and 3) in countries using the OPV, designed to limit the emergence of further VDPV2 strains and eliminate the risk of vaccine-associated paralytic poliomyelitis caused by Sabin 2.

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 Although most countries eliminated Sabin-like poliovirus type 2 (SL2) transmission following the switch, some cVDPV2 transmission continued, leading to sporadic cVDPV2 outbreaks as poliovirus type 2 mucosal immunity declined.

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 Sabin monovalent OPV type 2 (mOPV2) was used to address these outbreaks, but many such campaigns were delayed and provided insufficient coverage, leading to further emergence and transmission of cVDPV2.

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 The COVID-19 pandemic compounded the issue; routine polio vaccination, surveillance, and cVDPV2 outbreak response activities were suspended for 4 months in 2020 to protect communities and health workers, enabling further spread of cVDPV2.

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 Furthermore, many of the large cVDPV2 outbreaks have emerged in countries such as Afghanistan, which are beset by conflict, with highly mobile populations and inadequate health infrastructures.

The discovery of VDPV2 in London and New York (NY, USA) should come as a wake-up call. As the full extent of VDPV2 transmission in these cities is evaluated, the factors underlying such transmission in settings with exclusive inactivated polio vaccine (IPV) use, high national vaccine coverage, and good sanitation must also be fully assessed.

A possible explanation would be that VDPV2 has emerged following shedding and subsequent circulation of SL2 by individuals who were vaccinated overseas with Sabin mOPV2, and ongoing VDPV2 transmission is occurring in undervaccinated communities. Rockland (NY, USA), the county where a case of poliovirus has been identified, has routine childhood immunisation coverage of 42%, the lowest in New York,

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 and inactivated polio vaccine vaccination coverage in London has fallen in recent years, with coverage as low as 73·6% in some boroughs.

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 However, the finding of virus in sewage over several months from a large population and with high genetic diversity of the isolated viruses implies that transmission could be widespread.

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The USA and the UK have exclusively used IPV since 2000 and 2004, respectively.

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 Although two or more doses of IPV provide excellent humoral immunity, protecting fully-vaccinated individuals from developing poliomyelitis caused by all strains of poliovirus, including VDPV2, IPV is less effective than OPV at inducing intestinal mucosal immunity, meaning IPV-vaccinated individuals might theoretically be able to shed polioviruses in their stool, facilitating transmission.

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 However, there are currently few real-world data to evidence this, and the previous success of the IPV in eliminating polio in the Netherlands and Scandinavian countries suggests that a more complex picture of poliovirus immunity and VDPV2 transmission in London and New York might emerge.

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There is evolving evidence of genetic linkages between the polioviruses detected in London and New York, and also with SL2 viruses identified in sewage from Jerusalem in June, 2022.

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 Israel boasts high vaccination coverage with both the IPV and bivalent OPV (97·6% and 88·3% for the IPV and bivalent OPV, respectively), but despite this, has also recently identified circulating vaccine-derived poliovirus type 3, with one case of poliomyelitis occurring on March 7, 2022.

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The rise in VDPV2 transmission presents a conundrum for global polio eradication. Eradication of both wild polioviruses and VDPVs is dependent on complete interruption of transmission; this is assumed to be conditional on induction of robust mucosal immunity through use of the OPV. However, VDPV interruption cannot be completed until OPV use is ceased. A potential solution to this dilemma is the development of more genetically stable oral poliovirus vaccine strains, which are less likely to evolve into VDPVs. Indeed, in 2020, a novel OPV-2 (nOPV2) vaccine was granted Emergency Use Listing status by WHO and has since been used extensively in cVDPV2 outbreak settings, with surveillance data indicating a high likelihood of success without the same risk of emergence of cVDPV2 as with standard OPV.

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Both London and New York represent very different settings to those where nOPV2 is currently being deployed, with regard to both coverage and type of polio immunity, sanitation standards, and surveillance systems. It is, therefore, conceivable that alternative strategies could be sufficient to interrupt VDPV2 transmission and prevent cases of poliomyelitis in these settings. Intensified surveillance, catch-up IPV immunisation programmes with prioritisation of unvaccinated individuals, and IPV booster programmes might all have a part to play. However, there is limited precedent for the management of VDPV2 transmission in IPV-only vaccinated populations, and although there is promise with options such as nOPV2, the dynamics of response strategies in these settings remain to be fully evaluated.

Ultimately, the isolation of VDPV2 in both the UK and USA in recent weeks mandates three urgent interventions. First, poliovirus surveillance is needed in affected countries and more broadly in countries without any surveillance to understand the extent of VDPV2 transmission worldwide and to mount timely and appropriate responses. Second, an urgent emphasis must be placed on improving vaccination coverage; while polioviruses remain in circulation, all unvaccinated and undervaccinated individuals remain at risk of this paralysing disease, and inadequately immunised populations could be contributing to ongoing transmission in communities. Third, evaluation of interventions is needed to assess the extent to which improving coverage of the unvaccinated, using catch-up doses for the undervaccinated, giving extra booster doses in wider populations, or aligning regulatory and operational preparedness for use of live oral vaccines (such as the nOPV2) are needed to control these new and unexpected outbreaks. Building momentum to adequately fund the implementation of the Polio Eradication 2022–26 strategy will be key to permanently stopping polio transmission and the risk of paralysis everywhere.

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 Failure to get this right threatens the global progress towards polio eradication.

Source: The Lancet