Increasing intensity of enterovirus outbreaks projected with climate change.

Pathogens of the enterovirus genus, including poliovirus and coxsackieviruses, typically circulate in the summer months suggesting a possible positive association between warmer weather and transmission. Here we evaluate the environmental and demographic drivers of enterovirus transmission, as well as the implications of climate change for future enterovirus circulation. We leverage pre-vaccination era data on polio in the US as well as data on two enterovirus A serotypes in China and Japan that are known to cause hand, foot, and mouth disease. Using mechanistic modeling and statistical approaches, we find that enterovirus transmission appears positively correlated with temperature although demographic factors, particularly the timing of school semesters, remain important. We use temperature projections from Coupled Model Intercomparison Project Phase 6 (CMIP6) to simulate future outbreaks under late 21st-century climate change for Chinese provinces. We find that outbreak size increases with climate change on average, though results differ across climate models depending on the degree of wintertime warming. In the worst-case scenario, we project peak outbreaks in some locations could increase by up to 40%.

Wild poliovirus makes comeback in Afghanistan and Pakistan.

2024 target of ending all transmission will likely be missed.

Intestinal mucosal immunity is unimportant for polio eradication: the failure of oral polio vaccination.

AIMS: To explore if intestinal immunity induced by infection with live viruses in the oral poliovirus vaccine (OPV) is essential, necessary or even helpful in interrupting transmission of wild poliovirus (WPV) for global polio eradication. METHODS: We reviewed the biology of virus-host interactions in WPV infection and its alterations by OPV-induced immunity for direct evidence of the usefulness of intestinal immunity. We also explored indirect evidence by way of the effect of the inactivated poliovirus vaccine (IPV) on the biology and on transmission dynamics of WPV. RESULTS: Immunity, systemic and intestinal, induced by infection with WPV or vaccine viruses, does not prevent re-infection with WPV or vaccine viruses respectively, when exposed. Such re-infected hosts shed virus in the throat and in faeces and are sources of further transmission. Immunity protects against polio paralysis-hence reinfection always remain asymptommatic and silent. CONCLUSION: Vaccine virus-induced intestinal immunity is not necessary for polio eradication. The continued and intensive vaccination efforts using OPV under the assumption of its superiority over IPV have resulted in the well-known undesirable effects, namely vaccine associated paralytic polio and the emergence of de-attenuated circulating vaccine-derived polioviruses, in addition to the delay in completing global WPV eradication.

Persistent Transmission of Circulating Vaccine-Derived Poliovirus - Somalia, January 2017-March 2024.

Since the launch of the Global Polio Eradication Initiative in 1988, substantial progress has been made in the interruption of wild poliovirus (WPV) transmission worldwide: global eradication of WPV types 2 and 3 were certified in 2015 and 2019, respectively, and endemic transmission of WPV type 1 continues only in Afghanistan and Pakistan. After the synchronized global withdrawal of all serotype 2 oral poliovirus vaccines (OPVs) in 2016, widespread outbreaks of circulating vaccine-derived poliovirus type 2 (cVDPV2) have occurred, which are linked to areas with low population immunity to poliovirus. Officials in Somalia have detected ongoing cVDPV2 transmission since 2017. Polio vaccination coverage and surveillance data for Somalia were reviewed to assess this persistent transmission. During January 2017-March 2024, officials in Somalia detected 39 cVDPV2 cases in 14 of 20 regions, and transmission has spread to neighboring Ethiopia and Kenya. Since January 2021, 28 supplementary immunization activities (SIAs) targeting cVDPV2 were conducted in Somalia. Some parts of the country are security-compromised and inaccessible for vaccination campaigns. Among 1,921 children with nonpolio acute flaccid paralysis, 231 (12%) had not received OPV doses through routine immunization or SIAs, 95% of whom were from the South-Central region, and 60% of whom lived in inaccessible districts. Enhancing humanitarian negotiation measures in Somalia to enable vaccination of children in security-compromised areas and strengthening campaign quality in accessible areas will help interrupt cVDPV2 transmission.

Pólio: baixa cobertura vacinal e o risco iminente de novas infecções / Polio: low vaccination coverage and the imminent risk of new infections

A poliomielite, comumente chamada de pólio ou paralisia infantil, é uma doença viral altamente infecciosa que afeta principalmente crianças menores de 5 anos de idade. O vírus é transmitido de pessoa para pessoa, disseminado principalmente pela via fecal-oral ou, menos frequentemente, por fômites (água ou alimentos contaminados); sendo que o agente etiológico pode se espalhar rapidamente em áreas cujos sistemas de higiene e saneamento são precários. Também pode haver transmissão por meio de gotículas de secreções da garganta durante a fala, tosse ou espirro ( WHO, 20 22 a ; SBIm, 2022)

Polio, commonly called polio or infantile paralysis, is a highly infectious viral disease that primarily affects children under 5 years of age. The virus is transmitted from person to person, spread mainly by the fecal-oral route or, less frequently, by fomites (contaminated water or food); being that the agent etiologic disease can spread rapidly in areas where hygiene and sanitation systems are precarious. There may also be transmission through droplets of secretions from the throat during speech, coughing or sneezing (WHO, 20 22 a ; SBIm, 2022)

Updated Characterization of Poliovirus Transmission in Pakistan and Afghanistan and the Impacts of Different Outbreak Response Vaccine Options.

BACKGROUND: Pakistan and Afghanistan remain the only reservoirs of wild poliovirus transmission. Prior modeling suggested that before the coronavirus disease 2019 (COVID-19) pandemic, plans to stop the transmission of serotype 1 wild poliovirus (WPV1) and persistent serotype 2 circulating vaccine-derived poliovirus (cVDPV2) did not appear on track to succeed. METHODS: We updated an existing poliovirus transmission and Sabin-strain oral poliovirus vaccine (OPV) evolution model for Pakistan and Afghanistan to characterize the impacts of immunization disruptions and restrictions on human interactions (ie, population mixing) due to the COVID-19 pandemic. We also consider different options for responding to outbreaks and for preventive supplementary immunization activities (SIAs). RESULTS: The modeling suggests that with some resumption of activities in the fall of 2020 to respond to cVDPV2 outbreaks and full resumption on 1 January 2021 of all polio immunization activities to pre-COVID-19 levels, Pakistan and Afghanistan would remain off-track for stopping all transmission through 2023 without improvements in quality. CONCLUSIONS: Using trivalent OPV (tOPV) for SIAs instead of serotype 2 monovalent OPV offers substantial benefits for ending the transmission of both WPV1 and cVDPV2, because tOPV increases population immunity for both serotypes 1 and 2 while requiring fewer SIA rounds, when effectively delivered in transmission areas.

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.

The Early Evolution of Oral Poliovirus Vaccine Is Shaped by Strong Positive Selection and Tight Transmission Bottlenecks.

The emergence of circulating vaccine-derived polioviruses through evolution of the oral polio vaccine (OPV) poses a significant obstacle to polio eradication. Understanding the early genetic changes that occur as OPV evolves and transmits is important for preventing future outbreaks. Here, we use deep sequencing to define the evolutionary trajectories of type 2 OPV in a vaccine trial. By sequencing 497 longitudinal stool samples from 271 OPV2 recipients and household contacts, we were able to examine the extent of convergent evolution in vaccinated individuals and the amount of viral diversity that is transmitted. In addition to rapid reversion of key attenuating mutations, we identify strong selection at 19 sites across the genome. We find that a tight transmission bottleneck limits the onward transmission of these early adaptive mutations. Our results highlight the distinct evolutionary dynamics of live attenuated virus vaccines and have important implications for the success of next-generation OPV.

Disease Surveillance Investments and Administration: Limits to Information Value in Pakistan Polio Eradication.

In Pakistan, annual poliovirus investment decisions drive quantities of supplemental immunization campaigns districts receive. In this article, we assess whether increased spending on poliovirus surveillance is associated with greater likelihood of correctly identifying districts at high risk of polio with assignment of an elevated "risk ranking." We reviewed programmatic documents from Pakistan for the period from 2012-2017, recording whether districts had been classified as "high risk" or "low risk" in each year. Through document review, we developed a decision tree to describe the ranking decisions. Then, integrating data from the World Health Organization and Global Polio Eradication Initiative, we constructed a Bayesian decision network reflecting investments in polio surveillance and immunization campaigns, surveillance metrics, disease incidence, immunization rates, and occurrence of polio cases. We test these factors for statistical association with the outcome of interest-a change in risk rank between the beginning and the end of the one-year time period. We simulate different spending scenarios and predict their impact on district risk ranking in future time periods. We find that per district spending increases are associated with increased identification of cases of acute flaccid paralysis (AFP). However, the low specificity of AFP investment and the largely invariant ranking of district risk means that even large increases in surveillance spending are unlikely to promote major changes in risk rankings at the current stage of the Pakistan polio eradication campaign.

Reflections on Modeling Poliovirus Transmission and the Polio Eradication Endgame.

The Global Polio Eradication Initiative (GPEI) partners engaged modelers during the past nearly 20 years to support strategy and policy discussions and decisions, and to provide estimates of the risks, costs, and benefits of different options for managing the polio endgame. Limited efforts to date provided insights related to the validation of the models used for GPEI strategy and policy decisions. However, modeling results only influenced decisions in some cases, with other factors carrying more weight in many key decisions. In addition, the results from multiple modeling groups do not always agree, which supports selection of some strategies and/or policies counter to the recommendations from some modelers but not others. This analysis reflects on our modeling, and summarizes our premises and recommendations, the outcomes of these recommendations, and the implications of key limitations of models with respect to polio endgame strategy. We briefly review the current state of the GPEI given epidemiological experience as of early 2020, which includes failure of the GPEI to deliver on the objectives of its 2013-2018 strategic plan despite full financial support. Looking ahead, we provide context for why the GPEI strategy of global oral poliovirus vaccine (OPV) cessation to end all cases of poliomyelitis looks infeasible given the current state of the GPEI and the failure to successfully stop all transmission of serotype 2 live polioviruses within four years of the April-May 2016 coordinated cessation of serotype 2 OPV use in routine immunization.

Insights From Modeling Preventive Supplemental Immunization Activities as a Strategy to Eliminate Wild Poliovirus Transmission in Pakistan and Afghanistan.

Many countries use supplemental immunization activities (SIAs) with oral poliovirus vaccine (OPV) to keep their population immunity to transmission high using preventive, planned SIAs (pSIAs) and outbreaks response SIAs (oSIAs). Prior studies suggested that investment in pSIAs saved substantial health and financial costs due to avoided outbreaks. However, questions remain about the benefits of SIAs, particularly with the recent introduction of inactivated poliovirus vaccine (IPV) into routine immunization in all OPV-using countries. The mounting costs of polio eradication activities and the need to respond to oSIAs threatens the use of limited financial resources for pSIAs, including in the remaining countries with endemic transmission of serotype 1 wild poliovirus (WPV1) (i.e., Pakistan and Afghanistan). A recent updated global poliovirus transmission model suggested that the Global Polio Eradication Initiative (GPEI) is not on track to stop transmission of WPV1 in Pakistan and Afghanistan. We use the updated global model to explore the role of pSIAs to achieve WPV1 eradication. We find that unless Pakistan and Afghanistan manage to increase the quality of bivalent OPV (bOPV) pSIAs, which we model as intensity (i.e., sufficiently high-coverage bOPV pSIAs that reach missed children), the model does not lead to successful eradication of WPV1. Achieving WPV1 eradication, the global objectives of the GPEI, and a successful polio endgame depend on effective and sufficient use of OPV. IPV use plays a negligible role in stopping transmission in Pakistan and Afghanistan and most other countries supported by the GPEI, and more IPV use will not help to stop transmission.

Global Transmission of Live Polioviruses: Updated Dynamic Modeling of the Polio Endgame.

Nearly 20 years after the year 2000 target for global wild poliovirus (WPV) eradication, live polioviruses continue to circulate with all three serotypes posing challenges for the polio endgame. We updated a global differential equation-based poliovirus transmission and stochastic risk model to include programmatic and epidemiological experience through January 2020. We used the model to explore the likely dynamics of poliovirus transmission for 2019-2023, which coincides with a new Global Polio Eradication Initiative Strategic Plan. The model stratifies the global population into 72 blocks, each containing 10 subpopulations of approximately 10.7 million people. Exported viruses go into subpopulations within the same block and within groups of blocks that represent large preferentially mixing geographical areas (e.g., continents). We assign representative World Bank income levels to the blocks along with polio immunization and transmission assumptions, which capture some of the heterogeneity across countries while still focusing on global poliovirus transmission dynamics. We also updated estimates of reintroduction risks using available evidence. The updated model characterizes transmission dynamics and resulting polio cases consistent with the evidence through 2019. Based on recent epidemiological experience and prospective immunization assumptions for the 2019-2023 Strategic Plan, the updated model does not show successful eradication of serotype 1 WPV by 2023 or successful cessation of oral poliovirus vaccine serotype 2-related viruses.

Modeling Poliovirus Transmission in Borno and Yobe, Northeast Nigeria.

Beginning in 2013, multiple local government areas (LGAs) in Borno and Yobe in northeast Nigeria and other parts of the Lake Chad basin experienced a violent insurgency that resulted in substantial numbers of isolated and displaced people. Northeast Nigeria represents the last known reservoir country of wild poliovirus (WPV) transmission in Africa, with detection of paralytic cases caused by serotype 1 WPV in 2016 in Borno and serotype 3 WPV in late 2012. Parts of Borno and Yobe are also problematic areas for transmission of serotype 2 circulating vaccine-derived polioviruses, and they continue to face challenges associated with conflict and inadequate health services in security-compromised areas that limit both immunization and surveillance activities. We model poliovirus transmission of all three serotypes for Borno and Yobe using a deterministic differential equation-based model that includes four subpopulations to account for limitations in access to immunization services and dynamic restrictions in population mixing. We find that accessibility issues and insufficient immunization allow for prolonged poliovirus transmission and potential undetected paralytic cases, although as of the end of 2019, including responsive program activities in the modeling suggest die out of indigenous serotypes 1 and 3 WPVs prior to 2020. Specifically, recent and current efforts to access isolated populations and provide oral poliovirus vaccine continue to reduce the risks of sustained and undetected transmission, although some uncertainty remains. Continued improvement in immunization and surveillance in the isolated subpopulations should minimize these risks. Stochastic modeling can build on this analysis to characterize the implications for undetected transmission and confidence about no circulation.

Modeling Undetected Live Poliovirus Circulation After Apparent Interruption of Transmission: Borno and Yobe in Northeast Nigeria.

Silent circulation of polioviruses complicates the polio endgame by affecting the confidence with which we can certify successful eradication (i.e., the end of transmission everywhere) given a long enough period of time with active surveillance and no observed detections. The Global Polio Eradication Initiative continues to use three years without observing paralytic cases caused by wild poliovirus (WPV) infection as an indication of sufficient confidence that poliovirus circulation stopped (assuming good surveillance). Prior modeling demonstrated the complexities of real populations and the imperfect nature of real surveillance systems, and highlighted the need for modeling the specific last reservoirs of undetected circulation. We use a poliovirus transmission model developed for Borno and Yobe to characterize the probability of undetected poliovirus circulation once apparent die-out occurs (i.e., in the absence of epidemiological signals) for WPV serotypes 1 and 3. Specifically, we convert the model to a stochastic form that supports estimates of confidence about no circulation given the time since the last detected event and considering the quality of both immunization and surveillance activities for these states. We find high confidence of no WPV3 circulation, and increasing confidence of WPV1 circulation, which we anticipate will imply high confidence in the absence of any detected cases in mid-2020 so long as Borno and Yobe maintain similar or achieve improved conditions. Our results confirm that gaps in poliovirus surveillance or reaching elimination with borderline sufficient population immunity can substantially increase the time to reach a high confidence about no undetected poliovirus transmission.

Certifying the interruption of wild poliovirus transmission in the WHO African region on the turbulent journey to a polio-free world.

On Aug 25 2020, the Africa Regional Commission for the Certification of Poliomyelitis Eradication declared that the WHO African region had interrupted transmission of all indigenous wild polioviruses. This declaration marks the African region as the fifth of the six WHO regions to celebrate this extraordinary achievement. Following the Yaoundé Declaration on Polio Eradication in Africa by heads of state and governments in 1996, Nelson Mandela launched the Kick Polio out of Africa campaign. In this Health Policy paper, we describe the long and turbulent journey to the certification of the interruption of wild poliovirus transmission, focusing on 2016-20, lessons learned, and the strategies and analyses that convinced the Regional Commission that the African region is free of wild polioviruses. This certification of the WHO African region shows the feasibility of polio eradication in countries with chronic insecurity, inaccessible and hard-to-reach populations, and weak health systems. Challenges have been daunting and the sacrifices enormous-dozens of health workers and volunteers have lost their lives in the pursuit of a polio-free Africa.

Case of Poliomyelitis Caused by Significantly Diverged Derivative of the Poliovirus Type 3 Vaccine Sabin Strain Circulating in the Orphanage.

Significantly divergent polioviruses (VDPV) derived from the oral poliovirus vaccine (OPV) from Sabin strains, like wild polioviruses, are capable of prolonged transmission and neuropathology. This is mainly shown for VDPV type 2. Here we describe a molecular-epidemiological investigation of a case of VDPV type 3 circulation leading to paralytic poliomyelitis in a child in an orphanage, where OPV has not been used. Samples of feces and blood serum from the patient and 52 contacts from the same orphanage were collected twice and investigated. The complete genome sequencing was performed for five polioviruses isolated from the patient and three contact children. The level of divergence of the genomes of the isolates corresponded to approximately 9-10 months of evolution. The presence of 61 common substitutions in all isolates indicated a common intermediate progenitor. The possibility of VDPV3 transmission from the excretor to susceptible recipients (unvaccinated against polio or vaccinated with inactivated poliovirus vaccine, IPV) with subsequent circulation in a closed children's group was demonstrated. The study of the blood sera of orphanage residents at least twice vaccinated with IPV revealed the absence of neutralizing antibodies against at least two poliovirus serotypes in almost 20% of children. Therefore, a complete rejection of OPV vaccination can lead to a critical decrease in collective immunity level. The development of new poliovirus vaccines that create mucosal immunity for the adequate replacement of OPV from Sabin strains is necessary.

Review of poliovirus modeling performed from 2000 to 2019 to support global polio eradication.

INTRODUCTION: Over the last 20 years (2000-2019) the partners of the Global Polio Eradication Initiative (GPEI) invested in the development and application of mathematical models of poliovirus transmission as well as economics, policy, and risk analyses of polio endgame risk management options, including policies related to poliovirus vaccine use during the polio endgame. AREAS COVERED: This review provides a historical record of the polio studies published by the three modeling groups that primarily performed the bulk of this work. This review also systematically evaluates the polio transmission and health economic modeling papers published in English in peer-reviewed journals from 2000 to 2019, highlights differences in approaches and methods, shows the geographic coverage of the transmission modeling performed, identified common themes, and discusses instances of similar or conflicting insights or recommendations. EXPERT OPINION: Polio modeling performed during the last 20 years substantially impacted polio vaccine choices, immunization policies, and the polio eradication pathway. As the polio endgame continues, national preferences for polio vaccine formulations and immunization strategies will likely continue to change. Future modeling will likely provide important insights about their cost-effectiveness and their relative benefits with respect to controlling polio and potentially achieving and maintaining eradication.