Viruses cause a great number of infectious diseases with medical, veterinary, agricultural, social and economic impact. Their unique mechanisms to spread, overcome and resist the existing countermeasures require innovative and smart antiviral strategies such as the effective disinfection of enclosed environments with ensured broad-spectrum efficacy and minimized risks associated with handling liquid biocides. Formic acid (FA) is a well-established natural acaricide used in beehives with an antiviral potential; however, its application in a liquid form is hindered by severe corrosiveness and rapid, uncontrolled evaporation. This study describes a novel formulation of FA, using a cryogel carrier for achieving a vapor-phase inactivation of viruses, thus eliminating the need for direct contact between the disinfectant and the pathogen. Firstly, a poly(N-isopropylacrylamide) (PNIPAm) cryogel was synthesized by a procedure involving cryogenic treatment, photochemical crosslinking, and freeze-drying, and then the cryogel was swollen with 65% FA or ddH2O as a control. After an exposure of a panel of animal and human viruses to FA, evaporated by the polymer carrier for time intervals between 15 min and 12 h, they were neutralized completely as follows: Poliovirus (PV) as a surrogate for major bee viral pathogens for 60 min by 5.1 ∆lg; Feline calicivirus (FCV) for 60 min by 5.3 ∆lg; Adenovirus 5 (AdV5) for 12 h by 4.0 ∆lg; and Influenza virus A (IAV) for 15 min by 5.1 ∆lg. Results were recorded after titration, 48–72 h incubation, cytopathic effect estimation and NR uptake assay. Our results suggest that 65% FA, when delivered via the PNIPAm cryogel matrix, acts as a powerful agent for fumigation-like disinfection. This “dry” delivery strategy offers significant practical advantages: it eliminates the need for open liquid containers, prevents spill-related hazards, and provides an alternative for controlled, long-term release of active vapors.

Recombinant poliovirus (PV) virus-like particle (VLP) antigens mimic the conformation of the surface proteins in native PVs (i.e., serotype-specific D-antigen epitopes). Since they lack genomes and are non-infectious, PV-VLPs offer the promise of a safer, next-generation polio vaccine compared to traditional inactivated (IPV) or attenuated live (OPV) vaccines. Sandwich D-antigen ELISA formats are commonly used to measure the in vitro potency values (relative D-antigen content, DU/mL) of unadjuvanted trivalent IPV antigens. If IPV is formulated with aluminum-salt adjuvants, however, a pretreatment step (i.e., adjuvant dissolution or antigen desorption) is required, which may compromise antigen integrity during sample handling. This work describes the development of three competitive ELISAs to measure the relative D-antigen content of aluminum-salt adjuvanted PV-VLPs (Types 1, 2, 3) without the need for pretreatment. First, key assay parameters were established, including specificity, accuracy, precision, linearity, limit of quantification, and stability-indication. Next, preformulation characterization studies were performed with these methods including (1) rank-ordering the inherent thermal stability profiles of the PV-VLPs (Types 1 > 3 > 2) in-solution and adsorbed to an aluminum phosphate adjuvant (AdjuPhos™, AP) and (2) determining the effect of formulation variables on the thermal stability profiles of AP-adsorbed PV-VLPs including antimicrobial preservatives (thimerosal, 2-PE) and five different antigens present in pediatric combination vaccines (D, T, wP, Hib, Hep B). The development and application of three competitive D-antigen ELISAs were demonstrated, and future use in formulation and storage stability studies with the AP-adjuvanted, trivalent PV-VLPs (Types 1, 2, 3) is discussed with the long-term goal to develop a stable, efficacious, multi-dose, hexavalent combination vaccine presentation.

Poliovirus (PV) genome encodes a large single polyprotein that is processed by viral proteases to form an active replication complex through either cis or trans interactions between the viral proteins (i.e., interactions between viral proteins encoded on the same polyprotein molecule or between those encoded on different polyprotein molecules, respectively). In the processing of polyprotein, the cleavage of viral 3AB into 3A and 3B is unique, as it requires host factors (PI4KB/OSBP) and viral protease (3Cpro/3CDpro) in cultured cells (i.e., in vivo). Here, we show viral/host requirements for the cleavage of 3AB in vivo. In a polyprotein encoding 2BC3ABCD of PV, cleavage of 3AB requires the activity of PI4KB as well as the entire 3Dpol region; even a partial deletion of the 3Dpol region severely affects the cleavage in the polyprotein. The activity of OSBP and the binding activity of 3CDpro to negatively charged molecules are not required for the cleavage in the polyprotein. PV mutants with premature termination codons or in-frame deletions in the 3Dpol-coding region are generally quasi-infectious in trans-rescued replication with 3CDpro, causing extensive in-frame genome duplication or deletion. Surprisingly, some PV mutants lacking the C-terminal peptides of 3Dpol showed stable replication without any reversion in the presence of 3CDpro provided in trans; 3Dpol provided in trans could rescue the defect in 3AB cleavage via amino acid residues involved in 3Dpol-3AB and 3Dpol-3Dpol interactions, indicating a remarkable overlap with those required for the uridylylation of 3B. This work reveals novel roles of the 3Dpol region, offering insights into the polyprotein processing and recombination.

Novel oral polio vaccine type 2 (nOPV2) was used under the WHO emergency use listing for circulating vaccine-derived polio virus (cVDPV) outbreaks from 2021 to 2023. We assessed nOPV2 adverse events following immunization (AEFIs) and compared its safety profile to other vaccines using VigiBase. We descriptively analysed AEFIs to nOPV2 and other vaccines reported to VigiBase from January 1, 2010 to December 31, 2023. Proportional Reporting ratios (PRRs) at Medical Dictionary for Regulatory Activities (MedDRA) higher level group term (HLGT) compared signals of disproportionate reporting (SDR) between nOPV2 and two comparators. In total, 409 001 AEFIs were included (nOPV2 specific AEFIs: n = 18 911 [4.6%]), of which 54.0% males (n = 10 209) and 22.6% serious (n = 4283). Most events had resolved (n = 9418, 49.8%) or were resolving (n = 6239, 33.0%) at reporting. Body temperature conditions, gastrointestinal and respiratory tract-related events were most reported to nOPV2. Five 'novel', mostly non-serious SDRs were identified - oral soft tissue conditions (PRR: 2.47, 95% CI: 1.71-3.59), haemoglobinopathies (PRR: 31.53, 95% CI: 3.38-312.72), malabsorption conditions (PRR: 4.65, 95% CI: 1.79-12.09), neoplasm-related morbidities (PRR: 3.61, 95% CI: 1.44-9.11) and skin and subcutaneous tissue infections and infestations NEC (PRR: 3.55, 95% CI: 2.61-4.82). Among the serious events, nervous system-related events were reported more. nOPV2 appears to retain a positive safety profile in real-world use. We support its continued use for cVDPV outbreak response and advocate continued monitoring as coverage increases and reporting is no longer mandated.

BACKGROUNDMany countries use school-based vaccination for adolescent vaccination; it has been shown to reduce inequities in uptake compared with other delivery routes. In England, coverage for human papillomavirus (HPV), meningococcal groups A, C, W and Y (MenACWY) and tetanus, diphtheria and inactivated polio virus (Td/IPV) vaccine programmes exceeded 80% before the COVID-19 pandemic. However, recent data show declining uptake.AIMThis study examined the relationship between socio-economic deprivation and coverage over time.METHODSWe conducted an ecological analysis of first-dose coverage for HPV (females and males), MenACWY and TdIPV in adolescents across 150 local authorities in England from 2017 to 2024. Coverage data were linked to 2025 Index of Multiple Deprivation (IMD) scores. Associations between IMD quintile, academic year and vaccination coverage were estimated using beta regression models.RESULTSBetween 2020 and 2024, lower coverage was consistently associated with higher deprivation, and differences in coverage between the most and least deprived IMD quintiles more than doubled. In 2024 these differences were 17.7%, 18.2%, 16∙8% and 16.9% for HPV (females), HPV (males), MenACWY and Td/IPV, respectively. The consistency of these findings suggests the effect of deprivation on coverage is not vaccine-specific.CONCLUSIONWe demonstrated a consistent and strengthening association between coverage and deprivation across multiple adolescent school-based vaccination programmes in England over time. Contributory factors may be numerous, and further research is needed to understand which factors are driving trends for different populations. Addressing these inequalities will require sustained targeted interventions to improve awareness of and access to vaccination.

Alongside the development of antibiotics, vaccination is the medical innovation with arguably the greatest impact on human health. Testament to its success is the eradication of infectious diseases, such as smallpox, that devastated human populations for almost 4000 years. Live-attenuated vaccines (LAV), which retain the capacity for infection and replication, were the first to be developed and remain highly efficacious, underpinning successful human vaccination campaigns (e.g. polio virus, measles virus, yellow fever virus). The cost of this success is the capacity of LAVs to cause disease in a small proportion of recipients, typically owing to overt or previously unappreciated immunodeficiency. From the careful investigation of such rare events, major clinical and scientific lessons about human antiviral immunity have been drawn. Here, we review features of pathogenic LAV dissemination, which continue to inform our understanding of critical steps in the immune control of LAVs. We discuss recent data on specific variants identified in geographically isolated populations and reflect on more common phenocopies of these monogenic defects, with potential implications for vaccine practice and policy. Collectively, these insights may inform approaches to the growing population of individuals rendered more vulnerable to LAVs by aging, multimorbidity or medical intervention. They also serve to highlight the clinical need for therapeutic strategies to combat pathogenic LAV dissemination.

Effects of neonatal Vitamin A supplementation on response to vaccinations in early infancy.

Clusters of acute flaccid paralysis (AFP) caused by oral vaccine-derived poliovirus (VDPV) in 2022 and sporadic outbreaks in New York and Gaza highlight the ongoing risk of polio, alongside the persistent global threat posed by wild-type poliovirus. This study aims to develop and validate a quantitative reverse transcription PCR (RT-qPCR) panel that employs different primer-probe sets to simultaneously detect vaccine and wild-type poliovirus (WPV) in wastewater. Using an inactivated poliovirus vaccine (IPV) and engineered DNA fragments (eDNAf), the qPCR master mix (MM) performance, assay specificity, sensitivity (limit of detection, LOD), and recovery from IPV-spiked wastewater were evaluated. Compared with two-step RT-qPCR and qScript MM, one-step RT-qPCR with TaqMan MM improved sensitivity for the following polioviruses (PV): Sabin 1 in IPV and the eDNAf of Sabin 1, 2, and 3; WPV1 and WPV3; and poliovirus type 2 (any serotype 2). The LOD for Sabin 1 in IPV was 2.49 copies/PCR, while LODs for eDNAf of polio targets ranged from 1.06 to 3.12 copies/PCR. Sabin 1 recovery from IPV-spiked wastewater ranged from 10.26% to 57.27%. The RT-qPCR panel for poliovirus exhibited good specificity and sensitivity, with moderate viral recovery, enabling rapid implementation of wastewater monitoring for PV as needed.

A diphtheria-tetanus-acellular pertussis-inactivated polio combination vaccine (dTaP-IPV) was offered as part of the UK antenatal vaccination programme from 2012 to July 2024. Prior research established that infants of mothers who received a dTaP-IPV vaccine in pregnancy have significantly reduced poliovirus-specific neutralising antibodies after their primary immunisation series compared with infants of non-dTaP-IPV vaccinated mothers. We investigated whether sufficient poliovirus-specific neutralising antibody titres are achieved in these children following the pre-school dTaP-IPV booster vaccine. Poliovirus-specific neutralising antibody titres were measured, via a microneutralisation assay, prior to and following receipt of the pre-school booster vaccine in blood samples taken during an observational, cohort, multi-centre, open label phase IV extension study. Prior to the pre-school boost, children of mothers who received dTaP-IPV vaccines in pregnancy had lower geometric mean titres (GMT) of antibodies than children of unvaccinated mothers (4.3 vs 54.7, p=0.0001). However, following administration of the pre-school booster all children, regardless of maternal vaccination status achieved protective antibody titres (≥8), although children of vaccinated mothers still had lower GMTs (988 vs 2964, p=0.009). Administration of the preschool booster overcomes the polio virus immunity gap that develops following the primary vaccination series in children whose mothers received an antenatal dTaP-IPV vaccine versus unvaccinated mothers. Residual differences in post-booster titres warrant continued surveillance to assess their clinical relevance. Clinical trials registry:NCT03578120.

The Inactivated Polio Vaccine (IPV) protects against all strains of the polio virus and poses no risk of vaccine-associated paralytic poliomyelitis. However, its coverage remains below an optimal level in Sub-Saharan Africa (SSA), and instances of vaccine-derived poliovirus have been reported. While several studies explored vaccine coverage, research specifically focused on IPV in SSA remains limited. Hence, this study aimed to assess the coverage and determinants of IPV uptake among children 12–23 months of age. A secondary data analysis was conducted using data from the recent demographic and health survey in 20 SSA countries between 2016 and 2023. The study included a total weighted sample of 43,564 children aged 12–23 months. Due to the hierarchical nature of the data, multilevel logistic regression was employed to identify associated factors. Model fitness and comparison were assessed using the median odds ratio, intra-class correlation coefficient, proportional change in variance, and deviance. Adjusted Odds Ratios (AORs) with their 95% CI were computed. Variables with a P-value < 0.05 in the multivariable multilevel analysis were considered statistically significant. The pooled inactivated polio vaccine coverage was 65.01% with a 95% CI (55.44, 74.76). Maternal age 20–35 years (AOR = 1,08, 95% CI: 1.00, 1.18) and above 35 years (AOR = 1.22, 95%CI: 1.11, 1.34), maternal education at primary level (AOR = 1.30, 95% CI: 1.23,1.37), and secondary level or above (AOR = 1.87, 95% CI: 1.76, 1.99), marital status (married (AOR = 0.83, 95% CI: 0.75,0.90), and widowed/divorced (AOR = 0.85, 95% CI: 0.75, 0.95))), media exposure (AOR = 1.20, 95% CI: 1.14,1.25), antenatal visit 1–3 (AOR = 1.86, 95%CI: 1.72, 2.01) and ≥ 4 visit (AOR = 2.51, 95% CI: 2.33,2.70), postnatal care (AOR = 1.73, 95%CI: 1.65,1.82), delivery at a health facility(AOR = 1.86, 95%CI: 1.77,1.97), birth interval more than 48 months (AOR = 1.34, 95%CI: 1.24, 1.44), urban residence (AOR = 1.24, 95%CI: 1.17,1.31), high community female literacy (AOR = 1.68, 95%CI: 1.54,1.83) were statistically significant positive determinants of IPV uptake. Conversely, rich household wealth (AOR = 0.84, 95% CI: 0.79,0.89) showed an inverse association. In most SSA countries, the inactivated polio vaccine coverage among children aged 12–23 months is substantially below the WHO-recommended herd immunity threshold of 90%, as well as beneath the 2024 global coverage of 85%. To improve this, stakeholders should focus on public health interventions like investing in maternal education, promoting antenatal and postnatal care, strengthening health service delivery, and raising community awareness through social media. Additionally, vaccination programs should target underserved areas and include mobile vaccination services.

Erratum: The Public Health Implications of the Detection of Polio Virus in Gazan Sewage

Enteroviruses (EVs) are small, non-enveloped RNA viruses that can cause diverse clinical outcomes, particularly severe in patients with primary immunodeficiency (PID) due to their impaired ability to clear infections. This study aimed to characterize EV excretion among 138 Tunisian PID patients over a five-year period, to identify circulating EV serotypes and assess their genetic diversity. A total of 558 stool samples were collected and analyzed by virus isolation and intratypic differentiation using RT-qPCR. Molecular typing was performed through Sanger sequencing of the VP1 region and whole genome sequencing using Next-Generation Sequencing (NGS) technologies. Phylogenetic analysis was conducted using the Maximum Likelihood (ML) method. EVs were detected in 55 stool samples from 23 patients. The excretion kinetics of EVs ranged between 30 and 946 days. Thirteen serotypes were identified, including one Poliovirus (PV) and twelve Non-Polio Enteroviruses (NPEVs), predominantly belonging to species B. Two previously unreported serotypes in Tunisia were detected: Coxsackievirus A5 (CVA5) and Echovirus type 19 (E19). In addition, five patients presented enhanced susceptibility to the excretion of successive EV serotypes, and one patient exhibited a co-infection. A possible recombination event was identified in one patient involving Coxsackievirus B5 (CVB5), Coxsackievirus A9 (CVA9) and Coxsackievirus B1 (CVB1) sequences. Phylogenetic analysis showed close genetic relationships with European, American and Asian strains. These findings underscore the dynamic nature of EV circulation and the importance of ongoing molecular surveillance to detect emerging serotypes and guide public health strategies.

Introduction. Drinking water is an important strategic resource. Monitoring for the epidemiological safety of water bodies for sanitary and virological indicators involves concentrating large volumes of water (from 10 to 100 liters). The need to study samples of such volume requires revision, modernization, and unification of sanitary and virological methods and, above all, optimization of concentration processes, modes and methods of sample preparation, to increase their efficiency and reduce the time from the moment of water sampling to the beginning of its study.The aim of the study is to compare the efficiency of virus sorption using three different concentration methods: a cartridge with a glass fiber filter; an anion exchange resin; on a flow membrane filter module with tangential-radial movement of liquid with positively charged microfiltration polyamide membranes in microfiltration mode.Materials and methods. Test virus – polio vaccine virus Sabin 1 in concentrations of 2, 3, and 4 lg TCID50/10 l. Experimental reservoirs were prepared on the basis of dechlorinated tap water.Results. All three methods of sample preparation are suitable for the qualitative determination of the polio virus in tap water at a concentration of 2 lg TCID50/10 l and higher.Limitations. The effectiveness of the three methods of concentrating viruses from water was assessed using a qualitative method. The study was conducted using model reservoirs created on the basis of tap water from the centralized water supply network of Moscow.Conclusions. The method of concentrating viruses using the filtration method on a fiberglass cartridge filter for sample preparation can be recommended for use in conducting sanitary and virological research of water for the presence of pathogens of intestinal infections of a viral nature along with concentration methods using anion exchange resin; on a flow membrane filter module with tangential-radial fluid movement with positively charged microfiltration polyamide membranes in the microfiltration mode.Compliance with ethical standards. The study does not require the submission of a biomedical ethics committee opinion or other documents.Contribution: Abramov I.A. – study concept and design, experiments, literature and experimental data analysis, visualization, writing, design and editing of the manuscript; Nedachin A.E., Tymchuk S.N. – study concept and design, experiments, editing of the manuscript; Karbovnicaya K.V. – experiments. All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version.Conflict of interest. The authors declare no conflict of interest.Funding. The study was conducted under the agreement 01-12/03-24 dated March 19, 2024 with CJSC ROSSA.Received: February 13, 2025 / Revised: September 9, 2025 / Accepted: December 2, 2025 / Published: January 15, 2026

Global public health continues to be significantly threatened by infectious diseases, demanding the creation of reliable mathematical models for their investigation and management. Despite being on the verge of eradication, the polio virus is nevertheless a subject of worry owing to its possible return. In this study, the fractional differential equations with the Mittag-Leffler kernel are used as a modeling tool to investigate the polio virus epidemic disease. The non-local and memory-dependent aspects of the Polio virus transmission mechanism are captured by the Mittag-Leffler kernel. In comparison to conventional integer-order models, the resultant system of fractional differential equations offers a more realistic depiction of the dynamics of the epidemic. The results of this study shed light on the crucial elements driving the polio virus epidemic’s development and management, providing insightful information for public health measures. Analytical results establish the existence, uniqueness, and Hyers-Ulam stability of solutions, while numerical simulations confirm that fractional models outperform classical approaches in predicting epidemic trends. Furthermore, this research highlights the importance of fractional calculus in simulating and understanding the dynamics of infectious diseases, emphasizing the improved accuracy and practicality of fractional differential equations with the Mittag-Leffler kernel in epidemiological studies. These findings advance our knowledge of epidemic modeling and control, and they may also have implications for the control of other infectious diseases.

ObjectiveTo evaluate the performance of Ghana’s environmental surveillance (ES) system for poliovirus (PV) detection from 2018 to 2022 using standardised indicators developed by the WHO and the US Centers for Disease Control and Prevention.DesignA retrospective performance evaluation using 10 key indicators benchmarked against global targets for PV surveillance.SettingSeven regions across Ghana, participating in the national ES programme implemented under the Global Polio Eradication Initiative.Surveillance coverageWastewater sampling was conducted at designated ES sites, supported by field collection teams and laboratory personnel responsible for sample acquisition, processing and reporting of PV detection results.Outcome measuresDetection rates of PV and non-polio enteroviruses (NPEVs), timeliness of sample collection and reporting, data quality and system stability.ResultsA total of 738 wastewater samples were collected. The system demonstrated high sensitivity, detecting circulating vaccine-derived PV type 2 in 51 (6.9%) of samples, Sabin PV types 1 and 3 in 61 (9.5%) and 114 (17.8%), respectively, and NPEVs in 491 (66.5%) of samples. Over 80% of samples met the recommended 21-day collection-to-reporting time frame. Data quality exceeded the ≥80% threshold, and workflows remained stable throughout the evaluation period.ConclusionsGhana’s ES system for PV was found to be flexible, stable and effective in generating high-quality data for early detection and public health response. These findings underscore the system’s critical role in supporting polio eradication efforts and highlight its potential as a model for surveillance in similar settings.

Enterovirus 71 (EV71) is a primary etiological agent of hand-foot-mouth disease (HFMD) in children under 5 years of age and can cause severe neurological disorders even death. Therefore, elucidating the infection mechanism and pathogenicity of EV71 is essential for developing more effective and targeted therapies to prevent and control EV71-associated diseases. Here, we initially reported that the SUMO E3 ligase CBX4 is important for EV71 replication. Furthermore, we found that CBX4 interacts with the EV71 3D polymerase, and overexpression of CBX4 significantly extends the half-life of 3D, whereas knockdown of CBX4 reduces the stability of 3D protein. Subsequent investigations demonstrated that CBX4 mediates both SUMOylation and ubiquitination modifications of 3D, and treatment with protein SUMOylation inhibitor 2-D08 remarkably depresses EV71 replication and the expression of ectopically transfected 3D. The regulatory role of CBX4 and the effect of 2-D08 were also observed in other enteroviruses, including coxsackievirus B3 (CVB3) and poliovirus 1 (PV1). These findings revealed that CBX4 facilitates EV71 infection through inducing SUMOylation and stabilization of 3D polymerase, hinting its potential as a novel target for antiviral development.

Multiple African-origin circulating poliovirus-2 emergences identified in Israel: A reminder of an ongoing global challenge.

The polio virus has been almost completely eliminated worldwide due to the widespread use of the oral polio vaccine. However, in patients with primary immunodeficiencies (PID), protection after vaccination may be absent, which poses a threat of developing the disease. . Aim - to study the status of protection against poliomyelitis in patients with PID in order to improve immunization approaches. Materials and methods. Determination of total levels of antibodies against polioviruses was carried out in 53 children with PID and 25 immunocompetent children of the control group. Children with congenital immunodeficiencies were divided into two groups: 21 children with PID with preserved antibody production function and 32 children with PID with severe antibody deficiencies or combined immunodeficiencies, who received regular replacement therapy with intravenous immunoglobulin. Results. The majority (66.7%) of PID patients with preserved antibody production function had protective levels of specific antibodies against poliomyelitis, which was comparable to 60,0% of poliovirus-protected children in the control group. Only 37.5% of PID children receiving immunoglobulin replacement therapy had protective pretransfusion levels of poliomyelitis antibodies. Conclusions. Vaccination of children with PID with inactivated polio vaccine is important for the formation of a protective level of immunity in children with preserved antibody production function. Most children with severe hypogammaglobulinemia on replacement therapy with intravenous immunoglobulin have insufficient immune protection against polio at the time of the next dose of immunoglobulin, which requires optimization of the dose and regimen of the drug. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of an institution. For each child, the informed consent of its mother to participate in the study was obtained. The authors declare no conflict of interest.

Enteroviruses (EVs) are the leading cause of viral meningitis in children. Recent outbreaks of non-polio EVs, most notably EV-A71 and EV-D68, have been associated with a polio-like paralysis known as acute flaccid myelitis (AFM). The lack of relevant models that mimic the cellular and functional responses of these human-restricted pathogens has hampered the development of effective treatments. We have previously engineered human stem cell-derived assembloids that recapitulate the neuromuscular connections underlying muscle contractions by integrating human spinal cord/hindbrain organoids (hSpO) and human skeletal muscle. Here, we used organoids and assembloids to investigate polio and non-polio EV pathogenesis. Infection of assembloids with poliovirus (PV), EV-D68 and EV-A71 resulted in loss of muscle contraction for all three viruses, which could be prevented by treatment with an antiviral agent. Yet, despite the convergence on neuronal dysfunction, the cellular targets by which each virus acted differed. More specifically, single cell transcriptomic profiling uncovered divergent cell tropisms between the EVs, and live imaging experiments revealed different modes and kinetics of cell damage. Altogether, we describe a multi-cellular model that captures viral pathogenesis in a human and circuit-relevant context.

During January 2022–June 2023, Pakistan reported 21 Wild Polio Virus 1 (WPV1) cases, all of which occurred within districts in the south Khyber Pakhtunkhwa (KP) province. In May 2023, a special immunization campaign was conducted to reach all children under 5 years of age within 69 high-risk union councils (UCs) in six districts of south KP. The campaign comprised of three rounds, each lasting 8 days, that provided bivalent oral poliovirus vaccine (bOPV) as well as other vaccines using a site-to-site delivery strategy. Rounds 1, 2, and 3 were conducted in July 2023, August 2023, and April 2024, respectively. We conducted a post-campaign evaluation (PCE) survey following the first two rounds, to assess OPV receipt, using a multistage sampling design. We analyzed PCE data for the two first rounds to provide UC-level estimates of the proportions of children who did not receive bOPV and assessed reasons for non-vaccination. The PCE survey included 8,125 children from 67 UCs during round 1 and 7,726 children from 47 UCs during round 2. The median number of villages by UC was 8 for both rounds. The median number of children by village was 16 for round 1 and 19 for round 2. Overall, 16% of children missed bOPV (95% CI = 14–18%) for round 1 [estimated total of 39,983 children (95% CI = 34,775–45,808)]; and 15% (95% CI = 13–17%) for round 2 [estimated total of 24,257 children (95% CI = 21,355–27,474)]. Percentages and numbers of missed children varied widely among UCs during both rounds. Six UCs in the first round and four UCs in the second had ≥40% missed children. Reasons for non-vaccination were similar for each round, with operational reasons leading by >60%, followed by refusals (≥20%), and child not available (~10%). We found a high proportion of missed children during this special immunization intervention and identified the UCs with the greatest challenges. In these UCs, there is a need to design and implement comprehensive, tailored, and effective interventions for each reason why children missed vaccination.