Wastewater-based surveillance as a tool for public health action: SARS-CoV-2 and beyond.

Wastewater-based surveillance (WBS) has undergone dramatic advancement in the context of the coronavirus disease 2019 (COVID-19) pandemic. The power and potential of this platform technology were rapidly realized when it became evident that not only did WBS-measured SARS-CoV-2 RNA correlate strongly with COVID-19 clinical disease within monitored populations but also, in fact, it functioned as a leading indicator. Teams from across the globe rapidly innovated novel approaches by which wastewater could be collected from diverse sewersheds ranging from wastewater treatment plants (enabling community-level surveillance) to more granular locations including individual neighborhoods and high-risk buildings such as long-term care facilities (LTCF). Efficient processes enabled SARS-CoV-2 RNA extraction and concentration from the highly dilute wastewater matrix. Molecular and genomic tools to identify, quantify, and characterize SARS-CoV-2 and its various variants were adapted from clinical programs and applied to these mixed environmental systems. Novel data-sharing tools allowed this information to be mobilized and made immediately available to public health and government decision-makers and even the public, enabling evidence-informed decision-making based on local disease dynamics. WBS has since been recognized as a tool of transformative potential, providing near-real-time cost-effective, objective, comprehensive, and inclusive data on the changing prevalence of measured analytes across space and time in populations. However, as a consequence of rapid innovation from hundreds of teams simultaneously, tremendous heterogeneity currently exists in the SARS-CoV-2 WBS literature. This manuscript provides a state-of-the-art review of WBS as established with SARS-CoV-2 and details the current work underway expanding its scope to other infectious disease targets.

Modeling Poliovirus Transmission and Responses in New York State.

BACKGROUND: In July 2022, New York State (NYS) reported a case of paralytic polio in an unvaccinated young adult, and subsequent wastewater surveillance confirmed sustained local transmission of type 2 vaccine-derived poliovirus (VDPV2) in NYS with genetic linkage to the paralyzed patient. METHODS: We adapted an established poliovirus transmission and oral poliovirus vaccine evolution model to characterize dynamics of poliovirus transmission in NYS, including consideration of the immunization activities performed as part of the declared state of emergency. RESULTS: Despite sustained transmission of imported VDPV2 in NYS involving potentially thousands of individuals (depending on seasonality, population structure, and mixing assumptions) in 2022, the expected number of additional paralytic cases in years 2023 and beyond is small (less than 0.5). However, continued transmission and/or reintroduction of poliovirus into NYS and other populations remains a possible risk in communities that do not achieve and maintain high immunization coverage. CONCLUSIONS: In countries such as the United States that use only inactivated poliovirus vaccine, even with high average immunization coverage, imported polioviruses may circulate and pose a small but nonzero risk of causing paralysis in nonimmune individuals.

Progress in Access and Oral Polio Vaccine Coverage Among Children Aged <5 Years in Polio Campaigns After the Political Change in Afghanistan.

BACKGROUND: Warfare has long impeded vaccination programs in polio-endemic Afghanistan. We aimed to describe progress in access to children under 5, oral polio vaccine (OPV) coverage among children under 5 in nationwide polio campaigns, and polio surveillance performance indicators after the Islamic Republic of Afghanistan collapsed to Taliban forces in August 2021. METHODS: Trends in the number of wild poliovirus type 1 (WPV1) and circulating vaccine-derived poliovirus type 2 (cVDPV2) cases and surveillance indicators from 2015 to 2023, and trends in the OPV coverage in the November 2020-June 2022 polio campaigns, were described. RESULTS: From 2015 to mid-July 2020, 74 of 126 (58.7%) WPV1 cases were reported from inaccessible areas. In November 2020, 34.1% of target children under 5 were inaccessible; in November 2021 (the first postchange polio campaign), all were accessible. From November 2020, under-5 OPV coverage of 69.9% rose steadily to 99.9% in the May 2022 campaign. The number of cVDPV cases fell from 308 (2020) to zero (2022). June 2022's house-to-house OPV coverage was 34.2% higher than non-house-to-house modalities. Nonpolio acute flaccid paralysis and stool adequacy rates rose from 18.5/100 000 and 92.6% in 2020 to 24.3/100 000 and 94.4% in 2022, respectively. CONCLUSIONS: Children's inaccessibility no longer vitiates polio eradication; polio surveillance systems are less likely to miss any poliovirus circulation.

Epidemiological and Clinical Insights into the Enterovirus D68 Upsurge in Europe 2021-2022 and Emergence of Novel B3-Derived Lineages, ENPEN Multicentre Study.

Enterovirus D68 (EV-D68) infections are associated with severe respiratory disease and acute flaccid myelitis (AFM). The European Non-Polio Enterovirus Network (ENPEN) aimed to investigate the epidemiological and genetic characteristics of EV-D68 infections and its clinical impact during the fall-winter season of 2021-2022. From 19 European countries, 58 institutes reported 10 481 (6.8%) EV-positive samples of which 1004 (9.6%) were identified as EV-D68 (including 852 respiratory samples). Clinical data were reported for 969 cases; 78.9% of infections were reported in children (0-5 years); and 37.9% of cases were hospitalized. Acute respiratory distress was commonly noted (93.1%) followed by fever (49.4%). Neurological problems were observed in 6.4% of cases including 6 diagnosed with AFM. Phylodynamic/Nextstrain and phylogenetic analyses based on 694 sequences showed the emergence of 2 novel B3-derived lineages, with no regional clustering. In conclusion, we describe a large-scale European EV-D68 upsurge with severe clinical impact and the emergence of B3-derived lineages.

My Uncle Charlie.

This is a story about my uncle Charlie, who contracted paralytic polio at an early age, and the remembrances on my career trajectory as a virologist that will never be forgotten.

Disseminated Echovirus 11 infection in a newborn in the Province of Bolzano, Italy.

PURPOSE: Recently, cases of serious illness in newborns infected with Echovirus 11 have been reported in Europe, including Italy. Here, we report the case of a newborn diagnosed with disseminated Echovirus 11 infection, which occurred in October 2023 in the Province of Bolzano, Italy. METHODS: A molecular screening, by Real-Time RT-PCR, was employed to analyse the cerebrospinal fluid, blood and stool samples, and nasal swabs. The entire viral genome was sequenced using both Illumina and Nanopore technologies. RESULTS: The patient was admitted to hospital due to fever. Molecular testing revealed the presence of enterovirus RNA. Typing confirmed the presence of Echovirus 11. The patient was initially treated with antibiotic therapy and, following the diagnosis of enterovirus infection, also with human immunoglobulins. Over the following days, the patient remained afebrile, with decreasing inflammation indices and in excellent general condition. Genomic and phylogenetic characterization suggested that the strain was similar to strains from severe cases reported in Europe. CONCLUSIONS: Despite the low overall risk for the neonatal population in Europe, recent cases of Echovirus 11 have highlighted the importance of surveillance and complete genome sequencing is fundamental to understanding the phylogenetic relationships of Echovirus 11 variants.

Global polio eradication; can we replicate the smallpox success story?

Although the Global Polio Eradication Initiative has been largely successful in elimination of polio from various parts of the world, sporadic local outbreaks in non-endemic areas continue to pose a threat to global polio eradication efforts. In the two endemic countries, Pakistan and Afghanistan, a staggering 176 cases of wild poliovirus 1 (WPV1) were reported in 2019. In 2020 alone, 959 cases of Circulating Vaccine Derived Poliovirus 2 were reported globally from 27 countries. After staying polio-free for years, cases of WPV were detected in Malawi and Mozambique in 2022. The roots of the reported strains matched with the WPV strain from Pakistan. The emergence of WPV cases in Malawi and Mozambique underscores the fact that WPV still has the chance to spread beyond the Afghanistan-Pakistan region and sustained efforts are required for its complete eradication. In the case of smallpox, surveillance-containment was the key to eradication as many countries had already eradicated smallpox and the bigger concern was to track and contain any new cases emerging. Smallpox eradication followed a comprehensive plan which included elements like quality control and standardisation of vaccination protocols. Governments all over the world should prioritise immunisation drives, surveillance, and awareness campaigns to achieve the dream of a polio-free world.

Circulating vaccine derived polio virus type 2 outbreak and response in Yemen, 2021-2022, a retrospective descriptive analysis.

BACKGROUND: The outbreaks of circulating Vaccine Derived Polio Viruses (cVDPVs) have emerged as a major challenge for the final stage of polio eradication. In Yemen, an explosive outbreak of cVDPV2 was reported from August 2021 to December 2022. This study aims to compare the patterns of cVDPV2 outbreak, response measures taken by health authorities, and impacts in southern and northern governorates. METHOD: A retrospective descriptive study of confirmed cases of VDPV2 was performed. The data related to cVDPV2 as well as stool specimens and environmental samples that were shipped to WHO-accredited labs were collected by staff of surveillance. Frequencies and percentages were used to characterize and compare the confirmed cases from the southern and northern governorates. The average delayed time as a difference in days between the date of sample collection and lab confirmation was calculated. RESULTS: The cVDPV2 was isolated from 227 AFP cases reported from 19/23 Yemeni governorates and from 83% (39/47) of environmental samples with an average of 7 months delayed from sample collection. However, the non-polio AFP (NPAFP) and adequate stool specimen rates in the north were 6.7 and 87% compared to 6.4 and 87% in the south, 86% (195) and 14%(32) out of the total 227 confirmed cases were detected from northern and southern governorates, respectively. The first and second cases of genetically linked isolates experienced paralysis onset on 30 August and 1st September 2021. They respectively were from Taiz and Marib governorates ruled by southern authorities that started vaccination campaigns as a response in February 2022. Thus, in contrast to 2021, the detected cases in 2022 from the total cases detected in the south were lower accounting for 22% (7 of 32) of compared to 79% (155 of 195) of the total cases the north. CONCLUSION: A new emerging cVDPV2 was confirmed in Yemen. The result of this study highlighted the impact of vaccination campaigns in containing the cVDPV2 outbreak. Maintaining a high level of immunization coverage and switching to nOPV2 instead of tOPV and mOPV2 in campaigns are recommended and environmental surveillance should be expanded in such a risky country.

"Build back the confidence": qualitative exploration of community experiences with polio vaccination in the Covid-19 context in Cameroon and Ethiopia.

BACKGROUND: In 2020, as the Global Polio Eradication Initiative worked to address outbreaks of vaccine-derived poliovirus Type 2, particularly in sub-Saharan Africa, the Covid-19 pandemic suspended routine immunization campaigns worldwide. There were concerns about how Covid-19 - and the introduction of Covid-19 vaccines - might influence uptake of the oral polio vaccine (OPV). To inform communications strategies, we conducted a qualitative study to explore insights from community stakeholders into how Covid-19 influenced perceptions of OPV and vaccination campaigns. METHODS: We conducted 32 focus group discussions with caregivers of children under 5 and polio frontline workers as well as 22 in-depth interviews with healthcare practitioners and social influencers in Cameroon and Ethiopia. In each country, we purposively sampled stakeholders per discrete eligibility criteria from one urban (Yaoundé and Addis Ababa) and one peri-urban site (Bafia and Adama). RESULTS: We found that the Covid-19 pandemic and related precautionary measures introduced new challenges for OPV campaigns in Cameroon and Ethiopia, including reduced caregiver confidence in routine immunizations and an erosion of trust between caregivers and frontline workers. A salient concern among caregivers was that Covid-19 vaccines might be delivered in place of OPV. When asked how to maximize community support for future OPV campaigns, stakeholders suggested to rebuild caregiver trust for frontline workers; use a variety of information sources to ensure consistent messaging on vaccination reaches caregivers in a timely manner; increase remuneration, resources, and training for frontline workers; and leverage existing community influencers and groups. CONCLUSIONS: Despite the challenges to vaccination campaigns experienced during the Covid-19 pandemic, it was anticipated that the Polio Programme would continue to experience community support for OPV with appropriate messaging and community coordination. These efforts would "build back the confidence" among caregivers and other community stakeholders regarding community-based vaccination campaigns. Social and behavior change approaches that leverage clear, consistent messaging from multiple trusted platforms could address caregiver trust and dismantle mis/dis-information that creates confusion surrounding vaccines.

Evaluation of 17 years of MERIN (Meningitis and Encephalitis register in Lower Saxony, Germany) surveillance system: participants acceptability survey, completeness and timeliness of data.

BACKGROUND: A Meningitis and Encephalitis Surveillance (MERIN) was implemented in 2003 in Lower Saxony, Germany as an alternative to acute flaccid paralyses surveillance, as the latter did not reach WHO sensitivity criteria. The system provides information on circulating enterovirus (EV) serotypes by focussing on patients with suspected aseptic meningitis, encephalitis or acute flaccid paralysis and contributes to the national surveillance in documenting polio free status. MERIN is based on voluntary participation of hospitals. Therefore, our evaluation focusses on acceptability of the system's objectives and performance, and identifying areas for improvement. METHODS: To assess acceptability, 32 contributing hospitals were invited to an online-based survey (11/2021 to 01/2022) to rate the MERIN objectives, laboratory's performance, their workload, modes of processes and communication. Ideas for improvement were collected in open fields. In addition, data completeness and timeliness of laboratory diagnostics were assessed. RESULTS: Of 32 hospitals, 21 responded (66% response rate), sending 30 questionnaires, 25 from pediatric and 5 from neurological departments. High levels of satisfaction with the communication (≥ 96%), timeliness (≥ 81%), and distribution of the results (≥ 85%) were reported, 97% of participants judged the required workload as adequate. The median proportion of eligible patients included in MERIN was 75%. Participants gave rapid and reliable diagnostic testing the highest priority (96%), while monitoring of Germany's polio-free status was rated the lowest (61%). Providing medical reports digitally as well as regular updates about circulating EV serotypes were identified as areas for improvement. Data completeness of selected variables ranged from 78.3 to 99.9%. Median time between sample collection and arrival at laboratory was 2 days [IQR 1-3], EV diagnostics via PCR took one day [IQR 0-6] and EV isolation on cell culture 11 days [IQR 10-13]. CONCLUSION: MERIN is a highly accepted surveillance system. Its quality was enhanced further by addressing the suggested improvements such as regular reports on circulating EV serotypes and facilitating digital access to laboratory results. Our results emphasise the importance of recognizing and considering participants' motivations and expectations, and addressing their priorities, even if this is not the surveillance system's main focus. This approach can be applied to surveillance systems of other non-mandatory notifiable diseases.

Cost of integrated immunization campaigns in Nigeria and Sierra Leone: bottom-up costing studies.

BACKGROUND: To improve the efficient use of scarce resources, low- and middle-income countries and development partners are increasingly encouraged to deliver multiple vaccines and other interventions in a single integrated campaign. However, little is known regarding the cost of delivering vaccines through integrated campaigns, and the extent to which efficiencies are achieved. To fill this evidence gap, we estimated the cost of integrated immunization campaigns in Nigeria and Sierra Leone, and the potential savings from integration. METHODS: We conducted a retrospective ingredients-based costing study from a payer perspective of a campaign held in 2019 in Sierra Leone with measles-rubella vaccine and oral polio vaccine, during which nutrition supplements were also offered in part of the country, and yellow fever campaigns held in three states in Nigeria in 2019 and 2020, where in one state (Anambra) meningococcal A vaccines were co-delivered. We collected data from 108 health facilities, all relevant administrative levels, and implementing partners. We estimated the full financial and economic cost of each campaign, the average unit cost of delivery, as well as the cost by activity and resource type. We also estimated the cost savings from integration in Anambra state by modelling out the cost of the alternative of two standalone campaigns. RESULTS: The average financial delivery cost was $0.34 per dose in Sierra Leone, and the economic cost was $0.73 per dose. In Nigeria, the financial cost per dose was $0.29-$0.35 across the three states, and the economic cost per dose was $0.62-$0.85. Facilities and wards delivering more doses achieved a lower financial and economic unit cost of delivery, demonstrating evidence of economies of scale. We estimated that Anambra may have saved at least $1,204,133 in financial resources by integrating yellow fever and meningitis A vaccine delivery, amounting to $0.17 per dose delivered. When including opportunity costs, the economic cost saving was estimated at $0.34 per dose delivered. CONCLUSIONS: The study offers evidence on what it costs to deliver integrated campaigns, and shows that integrated delivery is likely to result in significant cost savings. Where high delivery volumes can be achieved, integrated campaigns can benefit from economies of scale. The findings can be used to inform planning and budgeting for immunization campaigns in low- and middle-income countries.

Introduction of a hexavalent vaccine containing acellular pertussis into the national immunization program for infants in Peru: a cost-consequence analysis of vaccination coverage.

BACKGROUND: Infant vaccination coverage rates in Peru have declined in recent years, exacerbated by the COVID-19 pandemic. Introduction of the fully-liquid diphtheria, tetanus, and acellular pertussis (DTaP)-inactivated polio vaccine (IPV)-hepatitis B (HB)-Haemophilus influenzae type B (Hib) hexavalent vaccine (DTaP-IPV-HB-Hib) in Peru's infant National Immunization Program may help improve coverage. We evaluated costs and healthcare outcomes, including coverage, of switching from a pentavalent vaccine containing whole-cell pertussis component (DTwP-HB-Hib) plus IPV/oral polio vaccine (IPV/OPV) to the hexavalent vaccine for the primary vaccination scheme (2, 4 and 6 months). METHODS: The analysis was performed over a 5-year period on a cohort of children born in Peru in 2020 (N = 494,595). Four scenarios were considered: the pentavalent plus IPV/OPV scheme (S1); replacing the pentavalent plus IPV/OPV scheme with the hexavalent scheme (S2); expanded delivery of the pentavalent plus IPV/OPV scheme (S3); expanded delivery of the hexavalent scheme (S4). Vaccine coverage and incidence of adverse reactions (ARs) were estimated using Monte Carlo simulations and previous estimates from the literature. Cases of vaccine-preventable diseases were estimated using a Markov model. Logistical and healthcare costs associated with these outcomes were estimated. Impact of key variables (including coverage rates, incidence of ARs and vaccine prices) on costs was evaluated in sensitivity analyses. RESULTS: The overall cost from a public health payer perspective associated with the pentavalent plus IPV/OPV vaccine scheme (S1) was estimated at $56,719,350, increasing to $61,324,263 (+ 8.1%), $59,121,545 (+ 4.2%) and $64,872,734 (+ 14.4%) in scenarios S2, S3 and S4, respectively. Compared with the status quo (S1), coverage rates were estimated to increase by 3.1% points with expanded delivery alone, and by 9.4 and 14.3% points, if the hexavalent vaccine is deployed (S2 and S4, respectively). In both scenarios with the hexavalent vaccine (S2 and S4), pertussis cases would also be 5.7% and 8.7% lower, and AR rates would decrease by 32%. The cost per protected child would be reduced when the hexavalent vaccine scheme. Incidence of ARs was an important driver of cost variability in the sensitivity analysis. CONCLUSIONS: Implementation of the hexavalent vaccine in Peru's National Immunization Program has a positive public health cost consequence.

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.

Coordinated global cessation of oral poliovirus vaccine use: Options and potential consequences.

Due to the very low, but nonzero, paralysis risks associated with the use of oral poliovirus vaccine (OPV), eradicating poliomyelitis requires ending all OPV use globally. The Global Polio Eradication Initiative (GPEI) coordinated cessation of Sabin type 2 OPV (OPV2 cessation) in 2016, except for emergency outbreak response. However, as of early 2023, plans for cessation of bivalent OPV (bOPV, containing types 1 and 3 OPV) remain undefined, and OPV2 use for outbreak response continues due to ongoing transmission of type 2 polioviruses and reported type 2 cases. Recent development and use of a genetically stabilized novel type 2 OPV (nOPV2) leads to additional potential vaccine options and increasing complexity in strategies for the polio endgame. Prior applications of integrated global risk, economic, and poliovirus transmission modeling consistent with GPEI strategic plans that preceded OPV2 cessation explored OPV cessation dynamics and the evaluation of options to support globally coordinated risk management efforts. The 2022-2026 GPEI strategic plan highlighted the need for early bOPV cessation planning. We review the published modeling and explore bOPV cessation immunization options as of 2022, assuming that the GPEI partners will not support restart of the use of any OPV type in routine immunization after a globally coordinated cessation of such use. We model the potential consequences of globally coordinating bOPV cessation in 2027, as anticipated in the 2022-2026 GPEI strategic plan. We do not find any options for bOPV cessation likely to succeed without a strategy of bOPV intensification to increase population immunity prior to cessation.

Thirteen-year surveillance results of acute flaccid paralysis cases in Southeast Turkey and the effect of refugee movements on surveillance results.

OBJECTIVE: Acute flaccid paralysis (AFP) is a major neurological problem. Turkey has accepted over 4 million refugees since 2011 due to the wars in neighbouring countries. In the long term, refugees can have adverse effects on the limited resources of health, sanitation, water supply, foodstuff, and shelter services of host countries, precipitating the transmission and spread of enteroviruses causing AFP. This study examines the 13-year surveillance and incidence of AFP cases in southeast Turkey, and questions possible impact of refugee movements on these parameters, comparing the periods before (2007-2010) and after (2011-2019) 2011, when the refugee movements emerged. METHODS: The records of cases reported from southeast part of Turkey with suspected AFP between January 2007 and December 2019 were reviewed retrospectively. RESULTS: Of the patients, 121 (58.5%) were male. Mean age was 80.36 ± 46.67 months. Eighty-five (41.1%) were aged 60 months or younger. The number of patients under 60 months increased significantly after 2011. Mean incidence was calculated as 0.88 cases/100,000 person years versus 1.58 cases/100,000 person years in the period before and after 2011, respectively. Guillain-Barré syndrome (GBS) was the most common cause of AFP in both periods. As of 2011, however, the incidence of acute transverse myelitis increased approximately 4 times and GBS decreased proportionally. Non-polio enteroviruses were the most frequent isolates, detected from 9.1% of stool samples. CONCLUSION: Although refugee movements appear to may have adverse effects on AFP incidence and surveillance outcomes, larger studies involving the whole country, particularly at places where no refugees settled, are needed to achieve more conclusive evidence.

Suspected Case of Persistent Thiamin Deficiency in a Hand-Reared Caribou Calf.

Hand-reared animals are invaluable and irreplaceable in studies of wildlife nutrition. Hand-rearing protocols provide insights into dietary and training programs, but less information is available on disease management. In young ruminants, thiamin (Vitamin B1) deficiency is a particularly important disease that is treatable early in the disease process, but otherwise can be fatal. In this husbandry report, we describe a case of suspected thiamin deficiency in a hand-reared calf (Rangifer tarandus granti) that resulted in clinical signs of polioencephalomalacia and persisted for > 3 months. We attempted treatment with thiamin injections; injections resolved clinical signs of disease, but clinical signs of disease returned once injections stopped. After > 2 months of thiamin injections, the caribou calf received a rumen transfaunation from a fistulated moose (Alces alces) housed at the same facility. Following rumen transfaunation, we did not observe signs of thiamin deficiency. The calf outgrew other females in the cohort initially and shows no long-term effects of thiamin deficiency or polioencephalomalacia. We recommend rumen transfaunation when thiamin deficiency is suspected and does not resolve with thiamin injections alone. We also recommend heterospecific donors if conspecific donors are not available.

Lessons From a House on Fire-From Smallpox to Polio.

Global burden of disease morbidity and mortality has shifted dramatically in the last 30 years from infectious to non-communicable diseases, leading to major improvements in global child survival and enhanced life expectancy for all age groups. Vaccination efforts worldwide have been key to this achievement, but with a reduction in vaccine preventable diseases, anti-vaccine sentiments have concurrently increased. Eradication of smallpox in 1977 is a testament to vaccination impacts on human health. Despite this historic success, recent increases in infectious disease outbreaks, such as polio and measles, especially among poorly vaccinated populations, have underscored the risks of resurgence of diseases once thought eliminated in the United States and elsewhere. Engaging governments, community leaders, and the public will be critical to continuing the advancement of global health through elimination of vaccine preventable diseases.

The Origins and Risk Factors for Serotype-2 Vaccine-Derived Poliovirus Emergences in Africa During 2016-2019.

Serotype 2 oral poliovirus vaccine (OPV2) can revert to regain wild-type neurovirulence and spread to cause emergences of vaccine-derived poliovirus (VDPV2). After its global withdrawal from routine immunization in 2016, outbreak response use has created a cycle of VDPV2 emergences that threaten eradication. We implemented a hierarchical model based on VP1 region genetic divergence, time, and location to attribute emergences to campaigns and identify risk factors. We found that a 10 percentage point increase in population immunity in children younger than 5 years at the campaign time and location corresponds to a 18.0% decrease (95% credible interval [CrI], 6.3%-28%) in per-campaign relative risk, and that campaign size is associated with emergence risk (relative risk scaling with population size to a power of 0.80; 95% CrI, .50-1.10). Our results imply how Sabin OPV2 can be used alongside the genetically stable but supply-limited novel OPV2 (listed for emergency use in November 2020) to minimize emergence risk.

Response to Vaccine-Derived Polioviruses Detected through Environmental Surveillance, Guatemala, 2019.

Guatemala implemented wastewater-based poliovirus surveillance in 2018, and three genetically unrelated vaccine-derived polioviruses (VDPVs) were detected in 2019. The Ministry of Health (MoH) response included event investigation through institutional and community retrospective case searches for acute flaccid paralysis (AFP) during 2018-2020 and a bivalent oral polio/measles, mumps, and rubella vaccination campaign in September 2019. This response was reviewed by an international expert team in July 2021. During the campaign, 93% of children 6 months <7 years of age received a polio-containing vaccine dose. No AFP cases were detected in the community search; institutional retrospective searches found 37% of unreported AFP cases in 2018‒2020. No additional VDPV was isolated from wastewater. No evidence of circulating VDPV was found; the 3 isolated VDPVs were classified as ambiguous VDPVs by the international team of experts. These detections highlight risk for poliomyelitis reemergence in countries with low polio vaccine coverage.

Animal Models of Enterovirus D68 Infection and Disease.

Human enterovirus D68 (EV-D68) is a globally reemerging respiratory pathogen that is associated with the development of acute flaccid myelitis (AFM) in children. Currently, there are no approved vaccines or treatments for EV-D68 infection, and there is a paucity of data related to the virus and host-specific factors that predict disease severity and progression to the neurologic syndrome. EV-D68 infection of various animal models has served as an important platform for characterization and comparison of disease pathogenesis between historic and contemporary isolates. Still, there are significant gaps in our knowledge of EV-D68 pathogenesis that constrain the development and evaluation of targeted vaccines and antiviral therapies. Continued refinement and characterization of animal models that faithfully reproduce key elements of EV-D68 infection and disease is essential for ensuring public health preparedness for future EV-D68 outbreaks.