Polio Endgame Research Articles

Antiviral Development for the Polio Endgame: Current Progress and Future Directions

As the world is approaching the eradication of wild poliovirus serotype 1, the last of the three wild types, the question of how to maintain a polio-free world becomes imminent. To mitigate the risk of sporadic vaccine-associated paralytic polio (VAPP) caused by oral polio vaccines (OPVs) that are routinely used in global immunization programs, the Polio Antivirals Initiative (PAI) was established in 2006. The primary goal of the PAI is to facilitate the discovery and development of antiviral drugs to stop the excretion of immunodeficiency-associated vaccine-derived poliovirus (iVDPV) in B cell-deficient individuals. This review summarizes the major progress that has been made in the development of safe and effective poliovirus antivirals and highlights the candidates that have shown promising results in vitro, in vivo, and in clinical trials.

Review of Poliovirus Transmission and Economic Modeling to Support Global Polio Eradication: 2020-2024.

Continued investment in the development and application of mathematical models of poliovirus transmission, economics, and risks leads to their use in support of polio endgame strategy development and risk management policies. This study complements an earlier review covering the period 2000-2019 and discusses the evolution of studies published since 2020 by modeling groups supported by the Global Polio Eradication Initiative (GPEI) partners and others. We systematically review modeling papers published in English in peer-reviewed journals from 2020-2024.25 that focus on poliovirus transmission and health economic analyses. In spite of the long-anticipated end of poliovirus transmission and the GPEI sunset, which would lead to the end of its support for modeling, we find that the number of modeling groups supported by GPEI partners doubled and the rate of their publications increased. Modeling continued to play a role in supporting GPEI and national/regional policies, but changes in polio eradication governance, decentralized management and decision-making, and increased heterogeneity in modeling approaches and findings decreased the overall impact of modeling results. Meanwhile, the failure of the 2016 globally coordinated cessation of type 2 oral poliovirus vaccine use for preventive immunization and the introduction of new poliovirus vaccines and formulation, increased the complexity and uncertainty of poliovirus transmission and economic models and policy recommendations during this time.

Uptake of fIPV3 and implementation challenges as perceived by auxiliary nurse midwives at two primary healthcare centers in urban Bengaluru: a mixed-method study

Background: India introduced fractional-dose inactivated poliovirus vaccine (fIPV) into its routine immunization program as part of the polio eradication and endgame strategic plan. The study aimed to assess the uptake of the 3rd dose of fIPV among eligible beneficiaries and explore the implementation challenges perceived by auxiliary nurse midwives (ANMs) at two primary healthcare centers in urban Bengaluru. Methods: A mixed-method study was conducted between April and May 2023. A cross-sectional design was used for quantitative objectives, while in-depth interviews were conducted with ANMs for qualitative insights. Data were collected through vaccination registers, questionnaires, and key informant interviews. The study population included all eligible beneficiaries for the 3rd dose of fIPV from January to March 2023. Results: Out of 296 eligible beneficiaries, 139 (47%) had received the 3rd dose of fIPV. The challenges faced by ANMs in fIPV3 implementation included difficulties in recording and reporting activities, fear of managing adverse events, lack of confidence in administering intradermal injections, obtaining consent from parents, inadequate training, and concerns about vaccine wastage and increased workload. Conclusions: The uptake of fIPV3 was suboptimal, and ANMs encountered several challenges during implementation. To enhance fIPV3 integration into the vaccination schedule, the health system needs to improve awareness among the community, strengthen health worker capacity, and provide better training and support. Strengthening routine immunization programs can contribute to sustained polio eradication efforts.

Health Economic Analysis of Antiviral Drugs in the Global Polio Eradication Endgame.

Polio antiviral drugs (PAVDs) may provide a critical tool in the eradication endgame by stopping poliovirus infections in immunodeficient individuals who may not clear the virus without therapeutic intervention. Although prolonged/chronic poliovirus excreters are rare, they represent a source of poliovirus reintroduction into the general population. Prior studies that assumed the successful cessation of all oral poliovirus vaccine (OPV) use estimated the potential upper bound of the incremental net benefits (INBs) of resource investments in research and development of PAVDs. However, delays in polio eradication, OPV cessation, and the development of PAVDs necessitate an updated economic analysis to reevaluate the costs and benefits of further investments in PAVDs. Using a global integrated model of polio transmission, immunity, vaccine dynamics, risks, and economics, we explore the risks of reintroduction of polio transmission due to immunodeficiency-related vaccine-derived poliovirus (iVDPV) excreters and reevaluate the upper bound of the INBs of PAVDs. Under the current conditions, for which the use of OPV will likely continue for the foreseeable future, even with successful eradication of type 1 wild poliovirus by the end of 2023 and continued use of Sabin OPV for outbreak response, we estimate an upper bound INB of 60 million US$2019. With >100 million US$2019 already invested in PAVD development and with the introduction of novel OPVs that are less likely to revert to neurovirulence, our analysis suggests the expected INBs of PAVDs would not offset their costs. While PAVDs could play an important role in the polio endgame, their expected economic benefits drop with ongoing OPV use and poliovirus transmissions. However, stakeholders may pursue the development of PAVDs as a desired product regardless of their economic benefits.HighlightsWhile polio antiviral drugs could play an important role in the polio endgame, their expected economic benefits continue to drop with delays in polio eradication and the continued use of oral poliovirus vaccines.The incremental net benefits of investments in polio antiviral drug development and screening for immunodeficiency-related circulating polioviruses are small.Limited global resources are better spent on increasing global population immunity to polioviruses to stop and prevent poliovirus transmission.

Worst-case scenarios: Modeling uncontrolled type 2 polio transmission.

In May 2016, the Global Polio Eradication Initiative (GPEI) coordinated the cessation of all use of type 2 oral poliovirus vaccine (OPV2), except for emergency outbreak response. Since then, paralytic polio cases caused by type 2 vaccine-derived polioviruses now exceed 3,000 cases reported by 39 countries. In 2022 (as of April 25, 2023), 20 countries reported detection of cases and nine other countries reported environmental surveillance detection, but no reported cases. Recent development of a genetically modified novel type 2 OPV (nOPV2) may help curb the generation of neurovirulent vaccine-derived strains; its use since 2021 under Emergency Use Listing is limited to outbreak response activities. Prior modeling studies showed that the expected trajectory for global type 2 viruses does not appear headed toward eradication, even with the best possible properties of nOPV2 assuming current outbreak response performance. Continued persistence of type 2 poliovirus transmission exposes the world to the risks of potentially high-consequence events such as the importation of virus into high-transmission areas of India or Bangladesh. Building on prior polio endgame modeling and assuming current national and GPEI outbreak response performance, we show no probability of successfully eradicating type 2 polioviruses in the near term regardless of vaccine choice. We also demonstrate the possible worst-case scenarios could result in rapid expansion of paralytic cases and preclude the goal of permanently ending all cases of poliomyelitis in the foreseeable future. Avoiding such catastrophic scenarios will depend on the development of strategies that raise population immunity to type 2 polioviruses.

Complexity of options related to restarting oral poliovirus vaccine (OPV) in national immunization programs after OPV cessation.

Background: The polio eradication endgame continues to increase in complexity. With polio cases caused by wild poliovirus type 1 and circulating vaccine-derived polioviruses of all three types (1, 2 and 3) reported in 2022, the number, formulation, and use of poliovirus vaccines poses challenges for national immunization programs and vaccine suppliers. Prior poliovirus transmission modeling of globally-coordinated type-specific cessation of oral poliovirus vaccine (OPV) assumed creation of Sabin monovalent OPV (mOPV) stockpiles for emergencies and explored the potential need to restart OPV if the world reached a specified cumulative threshold number of cases after OPV cessation. Methods: We document the actual experience of type 2 OPV (OPV2) cessation and reconsider prior modeling assumptions related to OPV restart. We develop updated decision trees of national immunization options for poliovirus vaccines considering different possibilities for OPV restart. Results: While OPV restart represented a hypothetical situation for risk management and contingency planning to support the 2013-2018 Global Polio Eradication Initiative (GPEI) Strategic Plan, the actual epidemiological experience since OPV2 cessation raises questions about what, if any, trigger(s) could lead to restarting the use of OPV2 in routine immunization and/or plans for potential future restart of type 1 and 3 OPV after their respective cessation. The emergency use listing of a genetically stabilized novel type 2 OPV (nOPV2) and continued evaluation of nOPV for types 1 and/or 3 add further complexity by increasing the combinations of possible OPV formulations for OPV restart. Conclusions: Expanding on a 2019 discussion of the logistical challenges and implications of restarting OPV, we find a complex structure of the many options and many issues related to OPV restart decisions and policies as of early 2023. We anticipate many challenges for forecasting prospective vaccine supply needs during the polio endgame due to increasing potential combinations of poliovirus vaccine choices.

Monovalent type 2 OPV (mOPV2) management in the field: Interventions and lessons learned.

The polio endgame strategy calls for ending the use of and removal of all Sabin vaccines globally given the risks of generation and spread of cVDPVs. With the successful eradication of wild poliovirus type 2 in 2015, the process of removing type 2 Sabin vaccines began with the switch from tOPV to bOPV across national vaccination programs. Following the tOPV to bOPV switch in April/May 2016, monovalent type 2 OPV (mOPV2) has been put into use in response to detected cVDPV2 polioviruses outbreaks. Between 31 May 2016 and 30 Jun 2020, 453 million doses of mOPV2 were provided to 21 countries to conduct 235 campaigns to respond to cVDPV2 outbreaks and high-risk events. However, the use of this vaccine paradoxically reintroduces live attenuated type 2 poliovirus into the populations and the environment, therefore, poses a risk for the emergence of new VDPV2s. Thus, it is critical to carefully and appropriately manage all in-country mOPV2 stocks utilized in outbreak response to minimize this risk. In this article, we examine the performance of mOPV2 vaccine management utilized for various outbreak responses after the switch.We present the major challenges faced and the lessons learned, to improve technical guidance and future response activities. Performance varied significantly across countries in terms of each of the activity areas evaluated. There were major gaps, especially in terms of vaccine accountability, and in many instances large numbers of vials went unaccounted presenting additional risk for further VDPV2 emergences. We have shown that especially at the beginning of implementation, insufficient attention has been given to mOPV2 vaccine management. Enhanced focus on mOPV2 vaccine management in line with the lessons learned presented in this paper should be a priority for public health programs and countries to consider and adapt in future VDPV2 responses as well as potential future activities associated with eventual complete withdrawal & cessation of OPV.These experiences can also be extended to other vaccines for which strict stock management and containment measures are required.

Effectiveness of a new vaccine for outbreak response and the increasingly complicated polio endgame

Achieving the eradication of poliomyelitis remains an elusive goal. More than 6 years after the globally-coordinated cessation of all use of type 2 oral poliovirus vaccines (OPV2) in routine immunisation, outbreaks caused by type 2 circulating vaccine-derived polioviruses (cVDPV2s) continue to paralyse children and young adults around the world.1 Since mid-2016, cVDPV2s have led to over 2650 reported cases of poliomyelitis (as of Oct 4, 2022),1 with the majority (67%) in Africa.2 A recent paralytic case (with onset of paralysis on June 20, 2022) in New York made the USA the 36th addition to the list of countries with reported cVDPV2 cases since 2016.

Health economic analysis of vaccine options for the polio eradication endgame: 2022-2036

ABSTRACT Background Multiple vaccine options are available for polio prevention and risk management. Integrated global risk, economic, and poliovirus transmission modeling provides a tool to explore the dynamics of ending all use of one or more poliovirus vaccines to simplify the polio eradication endgame. Research design and methods With global reported cases of poliomyelitis trending higher since 2016, we apply an integrated global model to simulate prospective vaccine policies and strategies for OPV-using countries starting with initial conditions that correspond to the epidemiological poliovirus transmission situation at the beginning of 2022. Results Abruptly ending all OPV use in 2023 and relying only on IPV to prevent paralysis with current routine immunization coverage would lead to expected reestablished endemic transmission of poliovirus types 1 and 2, and approximately 150,000 expected cases of poliomyelitis per year. Alternatively, if OPV-using countries restart trivalent OPV (tOPV) use for all immunization activities and end IPV use, the model shows the lowest anticipated annual polio cases and lowest costs. Conclusions Poor global risk management and coordination of OPV cessation remain a critical failure mode for the polio endgame, and national and global decision makers face difficult choices due to multiple available polio vaccine options and immunization strategies.

Novel Network Method Major Minor Variation Clustering Enables Identification of Poliovirus Clusters with High-Resolution Linkages.

The Global Polio Eradication Initiative uses an outbreak response protocol that defines type 2 Sabin or Sabin-like virus as those with 0-5 nucleotides diverging from their parental strain in the complete VP1 genomic region. Sabin or Sabin-like viruses share highly similar genome sequences, regardless of their origin. Thus, it is challenging to distinguish viruses at a higher resolution to detect polio clusters or trace sources for local transmissions of viruses at an early stage. To identify type 2 Sabin or Sabin-like sources and improve our ability to map viral sources to campaigns during the polio endgame, we investigated the feasibility of a new method for genetic sequence analysis. We named the method Major Minor Variation Clustering (MMVC), which uses a network model to simultaneously incorporate sequence similarity in major and minor variants in addition to onset dates to detect fine-scale polio clusters. Each identified cluster represents a collection of sequences that are highly similar in both major and minor variants, enabling the discovery of new links between viruses. By applying the method to a published data set collected in Nigeria during 2009-2012, we found that clusters identified using this method have several improvements over clusters derived from a phylogenetic tree approach. Integrative data analysis reveals that sequences in the same cluster have greater genomic similarities and better agreement with onset dates. As a complement to current phylogenetic tree approaches, MMVC has the potential to improve epidemiological surveillance and investigation precision to guide polio eradication.

Emerging challenges to realizing global polio eradication and their solutions

Background: The Global Polio Eradication Initiative (GPEI) promised to eradicate polio by 2000, yet the disease remains endemic in 2 countries. The current threat of resurgence in countries with low vaccine coverage and circulating vaccinederived poliovirus (cVDPV) outbreaks due to oral polio vaccine warrants a strategy review. Aims: To review the performance of the GPEI from a context based in Pakistan, identifying threats to success and suggesting strategy modifications to help achieve eradication. Methods: This was a desk review of the effectiveness of GPEI that was launched in 1988 to eradicate polio by 2000. Subsequent failure to eradicate led to multiple iterations in strategy and planning documents. These documents were reviewed alongside relevant literature to explore the reasons for failure and emergence of cVDPV. Results: GPEI has been effective in reducing the global polio disease burden by > 99%, but it remains endemic in Pakistan and Afghanistan. cVDPV has caused multiple outbreaks since 2000, and caused 7 times more cases than wild poliovirus (WPV) globally in 2020. The Polio Eradication and Endgame Strategic Plan 2013–2018 aimed to eradicate WPV and cVDPV simultaneously. In 2019, Pakistan saw an upsurge in WPV amid an outbreak of cVDPV infection that continued throughout 2020. Wild polio eradication was not realized and the country was unable to transition to inactivated polio vaccine as predicted in the strategic plan. Conclusion: Over 20 countries now report cVDPV outbreaks and many others are at risk. A country-specific modified strategy is required to eradicate WPV and cVDPV simultaneously, more so in endemic countries.

Health and Economic Outcomes Associated with Polio Vaccine Policy Options: 2019-2029.

The polio endgame remains complicated, with many questions about future polio vaccines and national immunization policies. We simulated possible future poliovirus vaccine routine immunization policies for countries stratified by World Bank Income Levels and estimated the expected costs and cases using an updated integrated dynamic poliovirus transmission, stochastic risk, and economic model. We consider two reference cases scenarios: one that achieves the eradication of all wild polioviruses (WPVs) by 2023 and one in which serotype 1 WPV (WPV1) transmission continues. The results show that the addition of inactivated poliovirus vaccine (IPV) to routine immunization in all countries substantially increased the expected costs of the polio endgame, without substantially increasing its expected health or economic benefits. Adding a second dose of IPV to the routine immunization schedules of countries that currently include a single IPV dose further increases costs and does not appear economically justified in the reference case that does not stop WPV transmission. For the reference case that includes all WPV eradication, adding a second IPV dose at the time of successful oral poliovirus vaccine (OPV) cessation represents a cost-effective option. The risks and costs of needing to restart OPV use change the economics of the polio endgame, although the time horizon used for modeling impacts the overall economic results. National health leaders will want to consider the expected health and economic net benefits of their national polio vaccine strategies recognizing that preferred strategies may differ.

Modeling and Managing Poliovirus Risks: We are Where we are….

This introduction for the third special issue on modeling poliovirus risks provides context for the current status of global polio eradication efforts and gives an overview of the individual papers included in the issue. Although risk analysis continues to support the Global Polio Eradication Initiative (GPEI), efforts to finish the job remained off track at the beginning of 2020 and prior to the COVID-19 pandemic, as discussed in the special issue. The disruptions associated with COVID-19 occurring now will inevitably change the polio eradication trajectory, and future studies will need to characterize the impacts of these disruptions on the polio endgame.

Evaluation of acute flaccid paralysis surveillance system, 2013 to 2017 – Bayelsa State, Nigeria

Background: Nigeria is one of the three countries where transmission of Wild Polio Virus (WPV) still occurs. Documented transmission occurs mainly in the northern part of the country. Acute flaccid paralysis (AFP) surveillance is one of polio eradication and endgame strategic plan. On this basis, we evaluated the AFP surveillance system in Bayelsa state, Nigeria with the aim of assessing the attributes of the system. Methods & Materials: We interviewed Stakeholders and reviewed AFP surveillance data from 2013 to 2017 using the updated CDC guidelines for evaluating the public health surveillance systems and the WHO performance standards to assess the performance of the system. Relevant data were extracted and analyzed using Microsoft Excel spreadsheet. Results: All 27 respondents knew that poliomyelitis was caused by a virus and they all felt that AFP case definition was easy to understand. 73% percent of them reported that completion of the Case Investigation Form (CIF) was simple. All the respondents were willing to continue to participate in the AFP surveillance. The non-polio AFP rate (12.3–16.6%) and stool specimen adequacy rate (98–100%) indicate high sensitivity. Proportion of AFP cases investigated within 48 h of notification, timely transportation, specimen arriving laboratory in good condition were all above WHO minimum standard of 80%. The surveillance system has dedicated staff from state ministry of health and support from National Stop Transmission of Polio (NSTOP). Conclusion: The AFP surveillance system in Bayelsa State is performing well. The system is useful, simple, flexible, acceptable, sensitive, representative, timely and stable. We recommended that regular training of data collectors should be implemented.

Acute flaccid paralysis surveillance system evaluation-Enugu state, Nigeria 2015–2018

Background: Nigeria is one of the three polio-endemic countries worldwide. Wild polio virus was reported last in Nigeria by August 2016 although pockets of circulating vaccine derived viruses’ infection and vaccine associated paralytic polio still occur. As part of the polio endgame strategy Nigeria targets to achieve and sustain optimum surveillance performance indicators in all States by December 2018. We evaluated the acute flaccid paralysis (AFP) surveillance system in Enugu State to assess if the target for these indicators are being met. Methods and materials: We used an adapted US CDC Updated Guidelines for Evaluating Public Health Surveillance Systems. We reviewed of AFP surveillance data collected 2015–2018. We conducted key informant interviews and focus group discussion with purposively selected stakeholders. We collected data from 30 randomly selected AFP Surveillance officers in the state using an adapted questionnaire and recorded frequencies and proportions of key indicators. Results: One compatible poliovirus case was identified in 2015 among the 1211 AFP cases recorded. The case definition of AFP and tools for reporting are simple. The system is mainly funded by foreign partners although the main challenge is sustainability. The system is unstable as there are few trained staff who are regularly assigned other duties or transferred to other departments other than AFP surveillance. The system is flexible, and accepted by all stakeholders. The sensitivity of the system measured by the annualized Non-Polio AFP (NPAFP) rate is 15.1 ± 2.7 (target of ≥2/100,000 population). The mean data quality was 94%, SD: 2.8 (target ≥90). Mean stool adequacy and timeliness of reporting were 83.9 ± 14.3% and 91.0 ± 8.6% respectively both having target of ≥80%. Case investigations done in ≤48 h: Mean 89 ± 7.4, non-polio enterovirus isolation rate: Mean 39.5 ± 19.4, target >10% and 60 days follow up Mean 85.2 SD (17.0). Conclusion: Enugu State AFP surveillance is meeting most of its target although stability of the system is suboptimal. We recommended that Enugu state government train a pool of health officers on AFP surveillance and reduce staff mobility. Enugu state government should also plan to have a budget line for surveillance of AFP, and take ownership of the surveillance structure.

Immunogenicity and safety of an adjuvanted inactivated polio vaccine, IPV-Al, in primary and booster trials in Asia, Central America and Europe

Background: Withdrawal of OPV and the widespread introduction of IPV is key in the Polio Endgame Strategy. This transition from OPV to IPV requires more and affordable IPV in quantities sufficient to secure at least two doses of IPV for every child. An adjuvanted inactivated polio vaccine (IPV-Al), obtained by adsorption of a reduced dose of inactivated poliovirus to an aluminium hydroxide adjuvant, can help mitigate global supply and cost constraints of IPV through dose-sparing. Aim: Investigation of immunogenicity and safety of IPV-Al compared to standard IPV: Methods and materials: Two primary vaccination phase 3 trials in infants vaccinated at 6, 10, 14 weeks and 9 months in the Philippines; at 2, 4, 6 months and 15–18 months in Panama. A Phase 2 primary vaccination trial in the Dominican Republic in infants vaccinated at 6, 10, 14 weeks. A Phase 1/2 booster vaccination trial in Denmark in children and adolescents (10–15 years) with a history of standard IPV vaccination. Results: Seroconversion rates (an antibody titre ≥4-fold higher than the estimated maternal antibody titre and a titre ≥8) evaluated one month after primary vaccination were: polio type 1, 96–98% (IPV-Al) versus 99–100% (IPV); type 2, 94–100% versus 99–100%; and type 3, 98–99% versus 99–100%. Non-inferiority of IPV-Al to IPV (predefined 10%-point margin) was confirmed in trials assessing primary immunogenicity. In infants, robust booster responses were demonstrated following a fourth polio vaccination and post-booster geometric mean titres (GMTs) were higher than post-priming GMTs. In the adolescent trial, robust booster responses were demonstrated following a fifth polio vaccination. IPV-Al was well tolerated with a safety profile comparable to that of standard IPV in the three trials. Conclusion: IPV-Al was demonstrated to be non-inferior to standard IPV for seroconversion following primary vaccination in the EPI schedule in Philippines and Dominican Republic, and at 2, 4, 6 months in Panama. Robust post-booster responses in 9-month-olds, 15–18-month-olds and 10–15-year-olds were demonstrated for IPV-Al. IPV-Al was safe and well tolerated. Results support the applicability of the dose-sparing adjuvanted IPV-Al vaccine to help secure a more affordable and stable supply of IPV for prevention of poliomyelitis as part of the global polio eradication initiative.

Lessons learned in the implementation of supplementary immunization activity (SIA) field guidelines for injectable vaccines – Experiences from Tanzania

BackgroundTo achieve Measles and Rubella elimination and Polio Endgame goals, Tanzania implemented country-wide integrated Supplementary Immunization Activities (SIAs) in October 2019 involving two injectable vaccines of MR and IPV. The SIAs targeted children aged between 9 and 59 months for Measles-Rubella and 18 to 42 months for IPV vaccines. This article aims to share lessons learnt in the implementation of SIAs field guidelines in Tanzania in 2019 to inform future implementation of the SIAs within and outside the country’s boundaries. MethodsFocus groups discussions (FGDs) were conducted among Regional Immunization and Vaccines Officers from all regions and National Supervisors and Partners responsible for implementing the SIAs. Key areas discussed were pre-planning activities, implementation, monitoring and evaluation of the SIAs based on key thematic areas including; planning and coordination, logistics management, trainings, and demand creation. Pre-described templates were used to guide the discussion and keep record of the discussions. ResultsThe SIAs achieved national target based on administrative coverage. This was due to a high sense of ownership of the SIAs and strong staff commitment to attain high coverage rates manifested through effective planning and coordination within and between levels; effective execution of SIAs activities; involvement of key stakeholders at all levels; and strong advocacy, communication and social mobilization activities. Despite the success observed through administrative coverage, the WHO target of attaining 95% coverage using the gold standard - national coverage survey, was not reached. The main barrier to success was inadequate and delayed disbursement of funding. ConclusionThe 2019 SIA achieved high administrative coverage as a result of effective coordination; adequate micro-planning; timely logistical preparations; and effective demand creation activities. Future campaigns need to give high priority to hard-to-reach and densely populated areas during planning and ensure timely disbursement of funds to the operational level during implementation.

Polio switch strategy: An obituary in the making?

India was certified free of polio in 2014. Until now, the oral polio vaccine (OPV) was being used in India. As the OPV is a live vaccine, vaccine-associated paralytic poliomyelitis may occur after its use. The aim is to replace the OPV with injectable polio vaccine. The Polio Eradication and Endgame Strategic Plan 2013–2018 has been made to eradicate polio. A switch from the trivalent OPV (tOPV) to bivalent OPV (bOPV) has been undertaken in all countries since April 2016. tOPV vials have been withdrawn and replaced by bOPV. In addition, the inactivated polio vaccine (IPV) has been introduced. The next step would be to remove the type 3 virus component followed by complete cessation of the OPV and a final switch to the IPV. The timeline has been fixed as 2018–2019. Replacement of a vaccine may raise fears in the community that need to be addressed. Re-emergence of circulating vaccine-derived poliovirus after withdrawal of the tOPV may occur. Proper disposal of vaccine vials needs to be ensured. Proper training of vaccinators is important. All stakeholders need to be incorporated, and focus should be more on deprived populations. The switch marks a significant step towards the final goal of polio eradication. Finally, the importance of community participation cannot be overemphasized. Sustained surveillance is the key to prevent occurrence of cases in polio-free countries through importation.

Expected Implications of Globally Coordinated Cessation of Serotype 3 Oral Poliovirus Vaccine (OPV) Before Serotype 1 OPV.

Globally coordinated cessation of all three serotypes of oral poliovirus vaccine (OPV) represents a critical part of a successful polio endgame, which the Global Polio Eradication Initiative (GPEI) plans to conduct in phases, with serotype 2 OPV cessation completed in mid 2016. Although in 2016 the GPEI expected to globally coordinate cessation of the remaining OPV serotypes (1 and 3) by 2021, continuing transmission of serotype 1 wild polioviruses to date makes those plans obsolete. With increasing time since the last reported polio case caused by serotype 3 wild poliovirus (in November 2012) leading to high confidence about its successful global eradication, the Global Commission for the Certification of Poliomyelitis Eradication recently certified its eradication. Questions now arise about the optimal timing of serotype 3 OPV (OPV3) cessation. Using an integrated global model that characterizes the risks, costs, and benefits of global polio policy and risk management options, we explored the implications of different options for coordinated cessation of OPV3 prior to COVID-19. Globally coordinating cessation of OPV3 as soon as possible offers the opportunity to reduce cases of vaccine-associated paralytic polio globally. In addition, earlier cessation of OPV3 should reduce the risks of creating serotype 3 circulating vaccine-derived polioviruses after OPV3 cessation, which represents a significant threat to the polio endgame given current GPEI plans to reduce preventive OPV supplemental immunization activities starting in 2019.

Updated Characterization of Post-OPV Cessation Risks: Lessons from 2019 Serotype 2 Outbreaks and Implications for the Probability of OPV Restart.

After the globally coordinated cessation of any serotype of oral poliovirus vaccine (OPV), some risks remain from undetected, existing homotypic OPV-related transmission and/or restarting transmission due to several possible reintroduction risks. The Global Polio Eradication Initiative (GPEI) coordinated global cessation of serotype 2-containing OPV (OPV2) in 2016. Following OPV2 cessation, the GPEI and countries implemented activities to withdraw all the remaining trivalent OPV, which contains all three poliovirus serotypes (i.e., 1, 2, and 3), from the supply chain and replace it with bivalent OPV (containing only serotypes 1 and 3). However, as of early 2020, monovalent OPV2 use for outbreak response continues in many countries. In addition, outbreaks observed in 2019 demonstrated evidence of different types of risks than previously modeled. We briefly review the 2019 epidemiological experience with serotype 2 live poliovirus outbreaks and propose a new risk for unexpected OPV introduction for inclusion in global modeling of OPV cessation. Using an updated model of global poliovirus transmission and OPV evolution with and without consideration of this new risk, we explore the implications of the current global situation with respect to the likely need to restart preventive use of OPV2 in OPV-using countries. Simulation results without this new risk suggest OPV2 restart will likely need to occur (81% of 100 iterations) to manage the polio endgame based on the GPEI performance to date with existing vaccine tools, and with the new risk of unexpected OPV introduction the expected OPV2 restart probability increases to 89%. Contingency planning requires new OPV2 bulk production, including genetically stabilized OPV2 strains.