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ABSTRACTBackground New York State (NYS) reported a polio case (June 2022) and outbreak of imported type 2 circulating vaccine-derived poliovirus (cVDPV2) (last positive wastewater detection in February 2023), for which uncertainty remains about potential ongoing undetected transmission.Research Design and Methods Extending a prior deterministic model, we apply an established stochastic modeling approach to characterize the confidence about no circulation (CNC) of cVDPV2 as a function of time since the last detected signal of transmission (i.e. poliovirus positive acute flaccid myelitis case or wastewater sample).Results With the surveillance coverage for the NYS population majority and its focus on outbreak counties, modeling suggests a high CNC (95%) within 3–10 months of the last positive surveillance signal, depending on surveillance sensitivity and population mixing patterns. Uncertainty about surveillance sensitivity implies longer durations required to achieve higher CNC.Conclusions In populations that maintain high overall immunization coverage with inactivated poliovirus vaccine (IPV), rare polio cases may occur in un(der)-vaccinated individuals. Modeling demonstrates the unlikeliness of type 2 outbreaks reestablishing endemic transmission or resulting in large absolute numbers of paralytic cases. Achieving and maintaining high immunization coverage with IPV remains the most effective measure to prevent outbreaks and shorten the duration of imported poliovirus transmission.

Background Achieving polio eradication requires ensuring the delivery of sufficient supplies of the right vaccines to the right places at the right times. Despite large global markets, decades of use, and large quantity purchases of polio vaccines by national immunization programs and the Global Polio Eradication Initiative (GPEI), forecasting demand for the oral poliovirus vaccine (OPV) stockpile remains challenging. Research design and methods We review OPV stockpile experience compared to pre-2016 expectations, actual demand, and changes in GPEI policies related to the procurement and use of type 2 OPV vaccines. We use available population and immunization schedule data to explore polio vaccine market segmentation, and its role in polio vaccine demand forecasting. Results We find that substantial challenges remain in forecasting polio vaccine needs, mainly due to (1) deviations in implementation of plans that formed the basis for earlier forecasts, (2) lack of alignment of tactics/objectives among GPEI partners and other key stakeholders, (3) financing, and (4) uncertainty about development and licensure timelines for new polio vaccines and their field performance characteristics. Conclusions Mismatches between supply and demand over time have led to negative consequences associated with both oversupply and undersupply, as well as excess costs and potentially preventable cases.

IntroductionDetection of poliovirus transmission and ongoing oral poliovirus vaccine (OPV) use continue to delay poliomyelitis eradication. In 2016, the Global Polio Eradication Initiative (GPEI) coordinated global cessation of type 2 OPV (OPV2) for preventive immunization and limited its use to emergency outbreak response. In 2019, GPEI partners requested restart of some Sabin OPV2 production and also accelerated the development of a genetically modified novel OPV2 vaccine (nOPV2) that promised greater genetic stability than monovalent Sabin OPV2 (mOPV2).MethodsWe reviewed integrated risk, economic, and global poliovirus transmission modeling performed before OPV2 cessation, which recommended multiple risk management strategies to increase the chances of successfully ending all transmission of type 2 live polioviruses. Following OPV2 cessation, strategies implemented by countries and the GPEI deviated from model recommended risk management strategies. Complementing other modeling that explores prospective outbreak response options for improving outcomes for the current polio endgame trajectory, in this study we roll back the clock to 2017 and explore counterfactual trajectories that the polio endgame could have followed if GPEI had: (1) managed risks differently after OPV2 cessation and/or (2) developed nOPV2 before and used it exclusively for outbreak response after OPV2 cessation.ResultsThe implementation of the 2016 model-based recommended outbreak response strategies could have ended (and could still substantially improve the probability of ending) type 2 poliovirus transmission. Outbreak response performance observed since 2016 would not have been expected to achieve OPV2 cessation with high confidence, even with the availability of nOPV2 prior to the 2016 OPV2 cessation.DiscussionAs implemented, the 2016 OPV2 cessation failed to stop type 2 transmission. While nOPV2 offers benefits of lower risk of seeding additional outbreaks, its reduced secondary spread relative to mOPV2 may imply relatively higher coverage needed for nOPV2 than mOPV2 to stop outbreaks.

Background: Investments made by countries and donors to support polio eradication and the Global Polio Eradication Initiative (GPEI) over the past 35 years provided financial support for significant health interventions beyond the prevention of polio. Prior economic analyses that sought to quantify the economic benefits of some interventions encountered insufficient data and evidence associated with non-polio-specific activities. The 2022-2026 GPEI Strategic Plan explicitly identified integration and gender equity as funded mandates that must move forward in parallel with polio eradication, but these goals remain vaguely defined from a health economic perspective. Methods: To ensure unambiguous and full accounting for all financial investments in the GPEI, polio eradication, and other desirable objectives, we identify the health economic analysis methods and inputs needed to ensure transparent financial accountability and cost-effective use of funds. Results: Sufficient inputs and methods exist to characterize the health and economic benefits of polio-specific activities, but we identified the need for additional information and method development for some non-polio-specific and cost-sharing activities. Donors who seek to support non-polio-specific objectives as part of the GPEI may want to provide dedicated support financing for which it may be difficult to apply typical health economic criteria and to expect net health and/or net economic benefits. Conclusions: Given the mixture of funding sources provided to the GPEI, which includes support by governments and private donors, we recommend that the GPEI separately account for financial needs that represent necessities for polio eradication from those used for other stated objectives. An added layer of specificity that identifies all funds according to each activity, the accountable party and/or parties, and the associated measurable health or other outcome(s), will enable improved health economic analyses and reporting to donors who seek to track returns on their investments.

Introduction: The inability to successfully stop all use of oral poliovirus vaccine (OPV) as part of the polio endgame and/or the possibilities of reintroduction of live polioviruses after successful OPV cessation may imply the need to restart OPV production and use, either temporarily or permanently. Areas covered: Complementing prior work that explored the risks of potential OPV restart, we discuss the logistical challenges and implications of restarting OPV in the future, and we develop appropriate assumptions for modeling the possibility of OPV restart. The complexity of phased cessation of the three OPV serotypes implies different potential combinations of OPV use long term. We explore the complexity of polio vaccine choices and key unresolved policy questions that may impact continuing and future use of OPV and/or inactivated poliovirus vaccine (IPV). We then characterize the assumptions required to quantitatively model OPV restart in prospective global-integrated economic policy models for the polio endgame. Expert commentary: Depending on the timing, restarting production of OPV would imply some likely delays associated with ramp-up, re-licensing, and other logistics that would impact the availability and costs of restarting the use of OPV in national immunization programs after globally coordinated cessation of one or more OPV serotypes.

Background: Silent circulation of polioviruses complicates the polio endgame and motivates analyses that explore the probability of undetected circulation for different scenarios. A recent analysis suggested a relatively high probability of unusually long silent circulation of polioviruses in small populations (defined as 10,000 people or smaller). Methods: We independently replicated the simple, hypothetical model by Vallejo et al. (2017) and repeated their analyses to explore the model behavior, interpretation of the results, and implications of simplifying assumptions. Results: We found a similar trend of increasing times between detected cases with increasing basic reproduction number (R0) and population size. However, we found substantially lower estimates of the probability of at least 3 years between successive polio cases than they reported, which appear more consistent with the prior literature. While small and isolated populations may sustain prolonged silent circulation, our reanalysis suggests that the existing rule of thumb of less than a 5% chance of 3 or more years of undetected circulation with perfect surveillance holds for most conditions of the model used by Vallejo et al. and most realistic conditions. Conclusions: Avoiding gaps in surveillance remains critical to declaring wild poliovirus elimination with high confidence as soon as possible after the last detected poliovirus, but concern about transmission in small populations with adequate surveillance should not significantly change the criteria for the certification of wild polioviruses. Keywords: Polio, Small populations, Silent circulation, Stochastic modeling

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.

In a recent study of electronic health records (EHR) of general practitioners in a livestock-dense area in The Netherlands in 2009, associations were found between residential distance to poultry farms and the occurrence of community-acquired pneumonia (CAP). In addition, in a recent cross-sectional study in 2494 adults in 2014/2015 an association between CAP and proximity to goat farms was observed. Here, we extended the 2009 EHR analyses across a wider period of time (2009-2013), a wider set of health effects, and a wider set of farm types as potential risk sources. A spatial (transmission) kernel model was used to investigate associations between proximity to farms and CAP diagnosis for the period from 2009 to 2013, obtained from EHR of in total 140,059 GP patients. Also, associations between proximity to farms and upper respiratory infections, inflammatory bowel disease, and (as a control disease) lower back pain were analysed. Farm types included as potential risk sources in these analyses were cattle, (dairy) goats, mink, poultry, sheep, and swine. The previously found association between CAP occurrence and proximity to poultry farms was confirmed across the full 5-year study period. In addition, we found an association between increased risk for pneumonia and proximity to (dairy) goat farms, again consistently across all years from 2009 to 2013. No consistent associations were found for any of the other farm types (cattle, mink, sheep and swine), nor for the other health effects considered. On average, the proximity to poultry farms corresponds to approximately 119 extra patients with CAP each year per 100,000 people in the research area, which accounts for approximately 7.2% extra cases. The population attributable risk percentage of CAP cases in the research area attributable to proximity to goat farms is approximately 5.4% over the years 2009-2013. The most probable explanation for the association of CAP with proximity to poultry farms is thought to be that particulate matter and its components are making people more susceptible to respiratory infections. The causes of the association with proximity to goat farms is still unclear. Although the 2007-2010 Q-fever epidemic in the area probably contributed Q-fever related pneumonia cases to the observed additional cases in 2009 and 2010, it cannot explain the association found in later years 2011-2013.