Background. An increase in the number of circulating vaccine-derived poliovirus (cVDPV) outbreaks has been reported worldwide in recent years, necessitating improved surveillance and diagnostic tools. The current standard protocol for polio detection is lengthy, labor-intensive, and inefficient for direct wastewater testing. Methods. Here we describe a multiplex poliovirus 2 (PV2)-specific assay that directly detects PV2 RNA derived from Sabin-2 vaccine in wastewater and stool samples. The new PV2-specific assay was used for direct detection of PV2 in environmental and clinical samples. Results. In silico analysis suggested that the assay is specific for PV2 originating from Sabin-2 vaccine and identifies 98.3% of available sequences, including some with <95% similarity to the vaccine reference sequence. We show that the assay is specific for PV2 and does not identify 19 other enterovirus strains, including Sabin-1 and Sabin-3 RNA. The new assay enabled fast detection of PV2 in suspected clinical samples, which was subsequently confirmed by isolation and sequencing. By analyzing 183 concentrated wastewater samples, we further show that the new assay specifically and directly identifies PV2 RNA, in the presence of PV1, PV3, and other enterovirus RNA. Conclusions. The assay provides quantitative results, allowing continuous monitoring of viral load dynamics. Comparison of the standard isolation protocol and the new assay showed excellent agreement in terms of specificity and sensitivity. This specific and rapid assay may therefore be a valuable tool for monitoring cVDPV2 outbreaks in real time, and promote global efforts for eradication and containment of poliovirus circulation.

Vaccine-derived polio virus (VDPV) strains can lead to acute flaccid paralysis (AFP), posing a significant challenge to public health and the eradication of poliovirus. In early 2025, two distinct cVDPV2 strains were identified in wastewater samples from separate regions in Israel as part of ongoing poliovirus environmental surveillance. Each strain was genetically linked to different African-origin emergences actively circulating in Africa. The first strain, detected in January in central Israel, was linked to the NIE-ZAS-1 emergence, while the second strain, identified one month later in Jerusalem, was genetically related to the SUD-RED-1 emergence. Whole-genome sequencing (WGS) and phylogenetic analyses revealed unique mutation patterns and recombination events, contributing valuable data for tracking further international detections of these strains. These events underscore the global risk of poliovirus importation and highlight the critical role of environmental surveillance in early detection.

We report the emergence and evolution of a circulating vaccine-derived poliovirus type 1 (cVDPV1) outbreak in Israel, linked to a vaccine-associated paralytic poliomyelitis case. Whole genome sequencing revealed a strong genetic link between the Sabin-like poliovirus type 1 variant from the case and pre-VDPV1 and VDPV1 isolated from environmental samples collected in October 2024–April 2025, mostly in Jerusalem. Early detection was made possible by Israel’s robust environmental surveillance and advanced sequencing technologies, enabling a rapid public health response.

Background An increase in the number of circulating vaccine derived poliovirus (VDPV) outbreaks is reported worldwide in recent years, necessitating improved surveillance and diagnostic tools. The current standard protocol for polio detection is lengthy, labor-intensive, and inefficient for direct wastewater testing. Methods Here we describe a multiplex poliovirus-2 (PV2) specific assay that directly detects PV2 RNA derived from Sabin-2 vaccine in wastewater and stool samples. The new PV2-specific assay was used for direct detection of PV2 in environmental and clinical samples. Results In-silico analysis suggested that the assay is specific for PV2 originated from Sabin-2 vaccine and identifies 98.3% of available sequences, including some with <95% similarity to the vaccine reference sequence. We show that the assay is specific for PV2 and does not identify 19 other enterovirus strains, including sabin-1 and Sabin-3 RNA. The new assay enabled fast detection of PV2 in suspected clinical samples, which was subsequently confirmed by isolation and sequencing. By analyzing 183 concentrated wastewater samples, we further show that the new assay specifically and directly identifies PV2 RNA, in the presence of PV1, PV3, and other enteroviruses RNA. Conclusions The assay provides quantitative results, allowing continuous monitoring of viral load dynamics. Comparison of the standard isolation protocol and the new assay showed excellent agreement in terms of specificity and sensitivity. This specific and rapid assay may therefore be a valuable tool for monitoring cVDPV2 outbreaks in real time, and promote the global efforts for eradication and containment poliovirus circulation

BACKGROUND:Similarly to wild poliovirus, vaccine-derived poliovirus (VDPV) strains can cause acute flaccid paralysis, posing a considerable challenge to public health and the eradication of poliovirus. VDPV outbreaks, particularly VDPV type 2 (VDPV2), are increasing worldwide, including in high-income countries with high vaccine coverage. We aimed to conduct a comprehensive analysis of the molecular epidemiology of a widespread VDPV2 outbreak in Israel in 2022-23 using conventional polio identification techniques and whole-genome sequencing. METHODS:In this genomic epidemiology study, we monitored and identified poliovirus type 2 (PV2) through the surveillance of stool samples from individuals with acute flaccid paralysis and related contacts, as well as environmental surveillance of sewage samples. Environmental surveillance involved 15 routine surveillance sites and an additional 30 sites dedicated to monitoring this outbreak, covering approximately 70% of Israel's population between April 1, 2022, and June 30, 2023. Additionally, we performed phylogenetic and mutation analyses using whole-genome, next-generation sequencing of PV2 isolates to identify recombination events, characterise VDPV2 lineages according to the capsid region, and establish the geographical distribution and linkage of PV2 isolates. FINDINGS:We detected 256 genetically linked samples from environmental surveillance, as well as one case of acute flaccid paralysis and four positive contacts associated with the Sabin type 2 oral vaccine strain. Most affected locations showed a high-density population of Jewish Ultra-Orthodox communities. Through high-resolution genomic characterisation and phylogenetic analysis of 202 representative sequences with complete capsid coverage, including isolates from both environmental surveillance and the case of acute flaccid paralysis, a conclusive linkage was established among all detections, confirming them to be part of a single VDPV2 outbreak. This strategy enabled the characterisation of three distinct lineages and established connections between different locations in Israel, including linking the case of acute flaccid paralysis and nearby environmental surveillance detections from the northern region with detections in the geographically distant central region. INTERPRETATION:This study highlights the role of environmental surveillance in the early detection and monitoring of poliovirus circulation, enabling a prompt public health response involving enhanced surveillance and a catch-up campaign with inactivated polio vaccine. Whole-genome sequencing offered valuable insights into the origins of the outbreak, linkage across detections, and the geographical distribution of the virus, with higher resolution than would have been possible with the standard analysis of the VP1 gene alone. FUNDING:None.

Evidence on unnecessary antibiotic use in children with acute viral gastroenteritis (AGE) is scarce. We characterized the extent and correlates of antibiotic use among children hospitalized with viral AGE. A single-center study enrolled children aged 0-59 months hospitalized for AGE between 2008 and 2015 in Israel. Information was collected on laboratory tests, diagnoses, antibiotic treatment, and rotavirus vaccination. Stool samples were tested for rotavirus antigen, GII-norovirus, and stool cultures were performed for bacterial enteropathogens. Data from 2240 children were analyzed. Rotavirus vaccine was given to 79% of eligible children. Rotavirus test was performed on 1419 (63.3%) children. Before the introduction of universal rotavirus vaccination (2008-2010), rotavirus positivity in stool samples was 37.0%, which declined to 17.3% during the universal vaccination years (2011-2015). Overall, 1395 participants had viral AGE. Of those, 253 (18.1% [95% CI 16.1-20.2]) had unnecessary antibiotic treatment, mostly penicillin 46.6%, ceftriaxone 34.0% and azithromycin 21.7%. A multivariable analysis showed an inverse association between rotavirus vaccination and unnecessary antibiotic treatment (odds ratio = 0.53 [95% CI 0.31-0.91]), while positive associations were found with performing chest-X-ray test (3.00 [1.73-5.23]), blood (3.29 [95% CI 1.85-5.86]) and urine cultures (7.12 [3.77-13.43]), levels of C-reactive protein (1.02 [1.01-1.02]) and leukocytes (1.05 [1.01-1.09]). The results were consistent in an analysis of children with laboratory-confirmed rotavirus or norovirus AGE, or after excluding children with CRP > 50 mg/L. In conclusion, antibiotic prescription was common among hospitalized children with viral AGE, which was inversely related to rotavirus vaccination, possibly due to less severe illness in the vaccinated children.

Wastewater treatment plants (WWTPs) provide vital services to the public by removing contaminants from wastewater prior to environmental discharge or reuse for beneficial purposes. WWTP workers occupationally exposed to wastewater can be at risk of respiratory or gastrointestinal diseases. The study objectives were to: (1) quantify pathogens and pathogen indicators in wastewater aerosols near different WWTP processes/unit operations, (2) develop a QMRA model for multi-pathogen and multi-exposure pathway risks, and (3) create a webbased application to perform and communicate risk calculations for wastewater workers. Case studies for seven different WWTP job tasks were performed investigating infection risk across nine different enteric and respiratory pathogens. It was observed that the ingestion risk among job tasks was highest for "walking the WWTP," which involved exposure from splashing, bioaerosols, and hand-to-mouth contact from touching contaminated surfaces. There was also a notable difference in exposure risk during peak (5:00am-9:00am) and non-peak hours (9:00am- 5:00am), with risks during the peak flow hours of the early morning assumed to be 5 times greater than non-peak hours. N95 respirator usage reduced median respiratory risks by 77 %. The developed tool performs multiple QMRA calculations to estimate WWTP workers' infection risks from accidental ingestion or inhalation of wastewater from multiple pathogens and exposure scenarios, which can inform risk management strategies to protect occupational health. However, more data are needed to reduce uncertainty in model estimates, including comparative data for pathogen concentrations in wastewater during peak and non-peak hours. QMRA tools will increase accessibility of risk models for utilization in decision-making.

Israel conducts routine environmental (15 sites) and acute flaccid paralysis (AFP) surveillance for poliovirus. During September 2021, increasing numbers of wastewater samples collected from more than one site in the Jerusalem region proved positive for ambiguous type 3 vaccine-derived poliovirus (aVDPV3), while environmental samples from remaining sampling sites were negative. In late February 2022, a VDPV3, genetically related to the Jerusalem environmental surveillance samples, was isolated from a stool sample collected from a non-immunodeficient, non-immunized child from Jerusalem who developed AFP, indicating that the aVDPV3s were circulating (cVDPV3s) rather than immunodeficiency-related VDPV3s (iVDPVs). In response to these isolations, the Israel Ministry of Health launched a catch-up immunization program.

The word “polio ” has been used to describe both a disease and the disease agent. Among current methods to measure the importance of or interest in a topic is to run a general web search for the term and to search the scientific literature in PubMed. A Google web search of the word “polio” in Aug 2010 yielded 31,100,000 hits, while a search in PubMed yielded 22,000 articles and 826 review articles. This review will concentrate on those aspects of the epidemiology of polio as it relates to disease eradication and the sustainability of this effort. The terms “polio” and “poliomyelitis ” will be used when describing the disease and “poliovirus” and related terms such as “polio vaccine ” will be used to describe the agent that causes the disease.

Children and adolescents with early onset autoimmune diseases have a different seasonality of month of birth than the general population. This pattern is consistent with an infection during pregnancy affecting the fetus or an infection immediately after birth that act as early triggers of the autoimmune diseases. We present data supporting the use of Rotavirus vaccinations in the reduction of incidence of childhood T1D and propose further investigations into whether other anti-virus vaccinations may reduce the burden of other autoimmune diseases such as multiple sclerosis, atopic dermatitis, psoriasis and subtypes of rheumatoid arthritis, Hashimoto thyroiditis.

ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Obesity is a risk factor for severe disease and mortality for both influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. While previous studies show that individuals with obesity generate antibody responses following influenza vaccination, infection rates within the obese group were twice as high as those in the healthy-weight group. The repertoire of antibodies raised against influenza viruses following previous vaccinations and/or natural exposures is referred to here as baseline immune history (BIH). To investigate the hypothesis that obesity impacts immune memory to infections and vaccines, we profiled the BIH of obese and healthy-weight adults vaccinated with the 2010-2011 seasonal influenza vaccine in response to conformational and linear antigens. Despite the extensive heterogeneity of the BIH profiles in both groups, there were striking differences between obese and healthy subjects, especially with regard to A/H1N1 strains and the 2009 pandemic virus (Cal09). Individuals with obesity had lower IgG and IgA magnitude and breadth for a panel of A/H1N1 whole viruses and hemagglutinin proteins from 1933 to 2009 but increased IgG magnitude and breadth for linear peptides from the Cal09 H1 and N1 proteins. Age was also associated with A/H1N1 BIH, with young individuals with obesity being more likely to have reduced A/H1N1 BIH. We found that individuals with low IgG BIH had significantly lower neutralizing antibody titers than individuals with high IgG BIH. Taken together, our findings suggest that increased susceptibility of obese participants to influenza infection may be mediated in part by obesity-associated differences in the memory B-cell repertoire, which cannot be ameliorated by current seasonal vaccination regimens. Overall, these data have vital implications for the next generation of influenza virus and SARS-CoV-2 vaccines. IMPORTANCE Obesity is associated with increased morbidity and mortality from influenza and SARS-CoV-2 infection. While vaccination is the most effective strategy for preventing influenza virus infection, our previous studies showed that influenza vaccines fail to provide optimal protection in obese individuals despite reaching canonical correlates of protection. Here, we show that obesity may impair immune history in humans and cannot be overcome by seasonal vaccination, especially in younger individuals with decreased lifetime exposure to infections and seasonal vaccines. Low baseline immune history is associated with decreased protective antibody responses. Obesity potentially handicaps overall responses to vaccination, biasing it toward responses to linear epitopes, which may reduce protective capacity. Taken together, our data suggest that young obese individuals are at an increased risk of reduced protection by vaccination, likely due to altered immune history biased toward nonprotective antibody responses. Given the worldwide obesity epidemic coupled with seasonal respiratory virus infections and the inevitable next pandemic, it is imperative that we understand and improve vaccine efficacy in this high-risk population. The design, development, and usage of vaccines for and in obese individuals may need critical evaluation, and immune history should be considered an alternate correlate of protection in future vaccine clinical trials.

Obesity is a risk factor of severe disease and mortality for both influenza and SARS-CoV-2. While previous studies show that obese individuals generate antibody responses following influenza vaccination, infection rates within the obese group were twice as high compared to the healthy-weight group. To investigate the hypothesis that obesity impacts immune memory to infections and vaccines, we profiled the baseline immune history of obese and healthy-weight adults vaccinated with 2010–11 seasonal influenza vaccine to influenza antigens. Despite extensive heterogeneity in baseline immune history profiles in both groups, there were striking differences between obese and healthy controls, especially towards A/H1N1 strains and the 2009 pandemic virus (Cal09). Individuals with obesity had lower IgG and IgA magnitude and breadth towards a panel of A/H1N1 whole viruses and hemagglutinin proteins from 1933–2009, but increased IgG magnitude and breadth towards linear peptides from the Cal09 H1 and N1 proteins. Age was also associated with A/H1N1 baseline immune history, with young individuals with obesity more likely to have reduced A/H1N1 baseline immune history. We further found that IgG baseline immune history was associated with baseline and post-vaccination protective antibody responses, as measured by micro-neutralization and hemagglutinin inhibition assays. Taken together our findings suggest that increased susceptibility of obese subjects to influenza infection may be in-part mediated by obesity-associated differences in the memory antibody repertoire, which cannot be ameliorated by seasonal vaccination. Overall, these data have vital implications for the next generation of influenza and SARS-CoV-2 vaccines.

Environmental pathogen surveillance is a sensitive tool that can detect early-stage outbreaks, and it is being used to track poliovirus and other pathogens. However, interpretation of longitudinal environmental surveillance signals is difficult because the relationship between infection incidence and viral load in wastewater depends on time-varying shedding intensity. We developed a mathematical model of time-varying poliovirus shedding intensity consistent with expert opinion across a range of immunization states. Incorporating this shedding model into an infectious disease transmission model, we analysed quantitative, polymerase chain reaction data from seven sites during the 2013 Israeli poliovirus outbreak. Compared to a constant shedding model, our time-varying shedding model estimated a slower peak (four weeks later), with more of the population reached by a vaccination campaign before infection and a lower cumulative incidence. We also estimated the population shed virus for an average of 29 days (95% CI 28–31), longer than expert opinion had suggested for a population that was purported to have received three or more inactivated polio vaccine (IPV) doses. One explanation is that IPV may not substantially affect shedding duration. Using realistic models of time-varying shedding coupled with longitudinal environmental surveillance may improve our understanding of outbreak dynamics of poliovirus, SARS-CoV-2, or other pathogens.

The emergence and international spread of neurovirulent circulating vaccine-derived polioviruses (cVDPVs) across multiple countries in Africa and Asia in recent years pose a major challenge to the goal of eradicating all forms of polioviruses. Approximately 90% of all cVDPV outbreaks are caused by the type 2 strain of the Sabin vaccine, an oral live, attenuated vaccine; cVDPV outbreaks typically occur in areas of persistently low immunization coverage (1). A novel type 2 oral poliovirus vaccine (nOPV2), produced by genetic modification of the type 2 Sabin vaccine virus genome (2), was developed and evaluated through phase I and phase II clinical trials during 2017-2019. nOPV2 was demonstrated to be safe and well-tolerated, have noninferior immunogenicity, and have superior genetic stability compared with Sabin monovalent type 2 (as measured by preservation of the primary attenuation site [domain V in the 5' noncoding region] and significantly lower neurovirulence of fecally shed vaccine virus in transgenic mice) (3-5). These findings indicate that nOPV2 could be an important tool in reducing the risk for generating vaccine-derived polioviruses (VDPVs) and the risk for vaccine-associated paralytic poliomyelitis cases. Based on the favorable preclinical and clinical data, and the public health emergency of international concern generated by ongoing endemic wild poliovirus transmission and cVDPV type 2 outbreaks, the World Health Organization authorized nOPV2 for use under the Emergency Use Listing (EUL) pathway in November 2020, allowing for its first use for outbreak response in March 2021 (6). As required by the EUL process, among other EUL obligations, an extensive plan was developed and deployed for obtaining and monitoring nOPV2 isolates detected during acute flaccid paralysis (AFP) surveillance, environmental surveillance, adverse events after immunization surveillance, and targeted surveillance for adverse events of special interest (i.e., prespecified events that have the potential to be causally associated with the vaccine product), during outbreak response, as well as through planned field studies. Under this monitoring framework, data generated from whole-genome sequencing of nOPV2 isolates, alongside other virologic data for isolates from AFP and environmental surveillance systems, are reviewed by the genetic characterization subgroup of an nOPV working group of the Global Polio Eradication Initiative. Global nOPV2 genomic surveillance during March-October 2021 confirmed genetic stability of the primary attenuating site. Sequence data generated through this unprecedented global effort confirm the genetic stability of nOPV2 relative to Sabin 2 and suggest that nOPV2 will be an important tool in the eradication of poliomyelitis. nOPV2 surveillance should continue for the duration of the EUL.

We report an emergence and increase in poliovirus type 2 detection via routine wastewater surveillance in three non-overlapping regions in the Jerusalem region, Israel, between April and July 2022. Sequencing showed genetic linkage among isolates and accumulation of mutations over time, with two isolates defined as vaccine-derived polioviruses (VDPV). This demonstrates the emergence and potential circulation of type 2 VDPV in a high-income country with high vaccine coverage and underscores the importance of routine wastewater surveillance during the polio eradication.

BACKGROUND:Poliovirus post-eradication containment of wild-type 2 poliovirus (PV2) requires the destruction of all materials containing, or potentially containing, PV2. Acute flaccid paralysis (AFP) cases in Israel between 1973 and 1988 were caused by all three serotypes; thus, isolates from cases and case-contacts were either PV2 or potentially contaminated with PV2.AIMS:To provide a proof-of-concept that whole genome sequences (WGS) of wild-type 3 poliovirus (PV3s) could be salvaged from the RNA extracted directly from archived poliovirus stocks avoiding re-amplification of neurovirulent viruses, we link WGSs to case histories and determine the phylogenetic relationships among the PV3s.METHODS:Data retrieved from 427 poliovirus-positive cases reported between 1973 and 1988 identified 85 PV3-associated cases. A total of 71 archived PV3 isolates were available from PV3-positive cases and contacts. WGSs were obtained by NGS from cDNA libraries constructed from RNA extracted directly from archived viral stocks. Sequences were subjected to phylogenetic analysis and linked to case data.RESULTS:WGSs were successfully constructed for 55 isolates. Phylogenetic analysis revealed the circulation of seven lineages of PV3. One lineage, with 23 isolates, presented as an outbreak of six-year duration. Isolates from six other lineages were consistent with subsequent separate introductions, sporadic cases, and limited transmission. Recombinant vaccine-like PV3 recombinants were isolated from some cases.CONCLUSIONS:Whole or near-whole genome sequence information, obtained from RNA extracted directly from the archived material, safely provided detailed genetic information linked to patient data from a time when limited sequence information was previously available and revealed the pattern of transmission of wild PV3 in Israel.