Publications by authors named "Lester Shulman"

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.

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  • * Prior to universal rotavirus vaccination, rotavirus was found in 37% of stool samples, which decreased to 17.3% after vaccination, and vaccination was linked to lower rates of unnecessary antibiotic prescribing.
  • * Factors associated with higher antibiotic use included chest X-ray and culture tests, along with elevated C-reactive protein and leukocyte levels, indicating that unneeded prescriptions were common in a hospital setting despite the introduction of rotavirus vaccination.
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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 web-based application to perform and communicate risk calculations for wastewater workers.

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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).

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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).

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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.

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  • The study focuses on the containment of wild-type 2 poliovirus (PV2) post-eradication, highlighting the need to destroy all materials that may contain it, while noting past cases of polio in Israel involved all three serotypes.
  • The researchers aimed to demonstrate that whole genome sequences (WGS) of wild-type 3 poliovirus (PV3) could be retrieved from archived samples without re-amplifying neurovirulent viruses, connecting these sequences to historical case data and their phylogenetic relationships.
  • They successfully generated WGS for 55 PV3 isolates, identifying seven distinct lineages, with one causing an outbreak over six years, and found recombinant vaccine-like PV3 strains in some cases, enhancing understanding
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  • Poliovirus type 2 was detected in wastewater samples from three different areas in Jerusalem between April and July 2022, indicating a rise in cases.
  • Genetic analysis revealed a connection among the viruses and the presence of mutations, with some identified as vaccine-derived polioviruses (VDPV).
  • This finding highlights the need for ongoing wastewater monitoring, even in countries with high vaccine coverage, to support polio eradication efforts.
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  • The rise of neurovirulent circulating vaccine-derived polioviruses (cVDPVs) in Africa and Asia presents a significant threat to global poliovirus eradication efforts, primarily caused by the type 2 strain from the Sabin oral vaccine in areas with low immunization rates.
  • To combat this, a new type 2 oral poliovirus vaccine (nOPV2) was developed, showing high safety, tolerability, and better genetic stability compared to the original vaccine, making it less likely to lead to vaccine-derived outbreaks.
  • The World Health Organization granted emergency use authorization for nOPV2 in November 2020 to address ongoing wild poliovirus transmission and cVDPV outbreaks, accompanied by a comprehensive monitoring plan for
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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.

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Response to and monitoring of viral outbreaks can be efficiently focused when rapid, quantitative, kinetic information provides the location and the number of infected individuals. Environmental surveillance traditionally provides information on location of populations with contagious, infected individuals since infectious poliovirus is excreted whether infections are asymptomatic or symptomatic. Here, we describe development of rapid (1 week turnaround time, TAT), quantitative RT-PCR of poliovirus RNA extracted directly from concentrated environmental surveillance samples to infer the number of infected individuals excreting poliovirus.

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Background: Recent studies showed that rotavirus vaccination may affect the prevalence of type 1 diabetes (T1D). The aim of the study was to determine the prevalence of early childhood (<5 years) T1D before and during the introduction of rotavirus vaccination in Israel by syndromic surveillance.

Methods: Data on insulin purchases reported by Israel's four Health Maintenance Organizations (HMOs) were retrieved from the National Program for Quality Indicators in Community Healthcare.

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As highlighted by the ongoing COVID-19 pandemic, vaccination is critical for infectious disease prevention and control. Obesity is associated with increased morbidity and mortality from respiratory virus infections. While obese individuals respond to influenza vaccination, what is considered a seroprotective response may not fully protect the global obese population.

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Recent epidemiological surveys performed in Australia, USA and Israel demonstrate that Rotavirus vaccination correlates with an attenuated prevalence and/or incidence of early childhood diabetes (T1D). Other studies failed to confirm the above.

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Background: Individuals with primary immune deficiencies (PIDs) may excrete poliovirus for extended periods and remain a major reservoir for polio after eradication. Poliovirus can spread by fecal-oral or oral-oral transmission. In middle- and high-income countries, oral-oral transmission may be more prevalent than fecal-oral transmission of polioviruses where PIDs patients survive longer.

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  • - This report highlights the first case of a persistent oropharyngeal infection with a type 2 poliovirus variant (iVDPV2) in a patient with primary immune deficiency, following the eradication of wild type 2 poliovirus.
  • - The iVDPV2 was found to persist not only in the throat but also in the gut, indicating its ability to survive in multiple locations within the body.
  • - The evolution of iVDPV2 in both the throat and gut occurred independently, raising concerns about the risk of oral and fecal transmission as the world aims for complete eradication of poliovirus type 2.
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Following the introduction of universal immunization against rotavirus, concerns were raised regarding pathogen-replacement of rotavirus by norovirus. The study aim was to examine the incidence and characteristics and norovirus gastroenteritis before and after the introduction of universal rotavirus immunization in Israel. We studied 1179 stool samples collected between November 2007 and December 2014 for a prospective hospital-based surveillance study of children aged 0-59 months hospitalized for gastroenteritis.

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  • In 2013-2014, Israel faced a wild poliovirus outbreak detected through sewage surveillance but did not report any paralysis cases, and the outbreak ended after a vaccination campaign.
  • Researchers developed a method to estimate WPV1 levels from qPCR data, leading to a revised understanding of the outbreak's timing and dynamics, suggesting it peaked earlier than previously thought.
  • The study found that about 59% of susceptible children were infected before the vaccination, and the campaign helped prevent around 10% of infections, highlighting the importance of environmental monitoring in global polio eradication efforts.
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Environmental surveillance (EnvS) is an important tool for monitoring the presence of poliovirus in endemic and poliovirus free regions. Unlike acute flaccid paralysis (AFP) surveillance, EnvS can monitor large populations using small numbers of samples and detect the introduction of poliovirus even before the appearance of AFP cases. Early detection and timely response can prevent the onset of poliovirus associated AFP, as was demonstrated by silent poliovirus transmission in Israel in 2013.

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An improved quantitative multiplex one-step RT-PCR (qmosRT-PCR) for simultaneous identification and quantitation of all three serotypes of poliovirus is described. It is based on using serotype-specific primers and fluorescent TaqMan oligonucleotide probes. The assay can be used for high-throughput screening of samples for the presence of poliovirus, poliovirus surveillance and for evaluation of virus shedding by vaccine recipients in clinical trials to assess mucosal immunity.

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Infants with severe combined immunodeficiency (SCID) are at risk of developing severe life-threatening infections if they are inadvertently given attenuated live vaccines. Concomitant appearance of two live vaccine-associated complications in one person is rarely reported. In this study, we present two SCID infants, who received BCG and oral polio vaccines according to their local immunization schedule early in life, before the diagnosis of immunodeficiency was made.

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Deep sequencing was used to determine complete nucleotide sequences of echovirus 11 (EV11) strains isolated from a chronically infected patient with CVID as well as from cases of acute enterovirus infection. Phylogenetic analysis showed that EV11 strains that circulated in Israel in 1980-90s could be divided into four clades. EV11 strains isolated from a chronically infected individual belonged to one of the four clades and over a period of 4 years accumulated mutations at a relatively constant rate.

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Background: Since mid-August 2014, North America experienced a wide outbreak of Enterovirus D68 (EV-D68) associated with severe respiratory illness in children. Several other countries also reported cases of EV-D68 in 2014.

Objectives: The aim of this study was to determine whether EV-D68 circulated in Israel in 2014, caused severe respiratory illness in children and was the causative agent of Acute Flaccid Paralysis.

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