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Background Two SARS-CoV-2 waves in Israel ended while a substantial number of individuals remained unvaccinated or partially vaccinated. The indirect protective effect of the first BNT162b2 vaccination campaign in Israel was evaluated between 22 December 2020 and 18 May 2021. Methods The daily percentage of new polymerase chain reaction (PCR)–confirmed SARS-CoV-2 cases among unvaccinated individuals was analyzed for trends. Major shifts were identified using piecewise linear regression analysis. At these shifts, the percentage of naturally vaccinated (past SARS-CoV-2 cases) and the percentage of actively vaccinated (by inoculation) individuals were weighted and summed to determine the percentage of natural and active vaccination (NAV). Results A first decline among unvaccinated individuals occurred during a lockdown period, when the percentage of NAV was 8.16%. The major decline occurred after the end of the lockdown when the percentage of NAV reached 52.05%. SARS-CoV-2 cases ultimately declined among unvaccinated individuals when the percentage of NAV reached 63.55%. During the study period, the Alpha variant was prevalent and the use of nonpharmaceutical interventions, including social distancing, existed to varying degrees. Conclusions The vaccination campaign played a major role in the decline of SARS-CoV-2 infection among unvaccinated individuals, leading to the end of the first 2021 SARS-CoV-2 wave (Alpha variant) in Israel. Infection in unvaccinated individuals stopped when two-thirds of the population were naturally or actively vaccinated. Any change in characteristics of the virus or the population can lead to a new outbreak.

Background: Previous studies described a higher prevalence of cardiovascular comorbidities during the winter season. Data regarding seasonal association of atrioventricular (AV) block are scarce. Methods: A retrospective cohort analysis of all patients admitted to a tertiary medical center with AV block requiring a permanent pacemaker (PPM) implantation between 2006-2017 was performed. In a time-series analysis, the seasonal incidence of PPM implementations due to AV block was assessed and adjusted for meteorological factors. The association between the weekly incidence of PPM implantations and the weekly rates of influenza as reported by the Israel Center of Disease Control (ICDC) were also assessed. Result: The study population included 759 patients. Mean age was 76.1 years and 55% were males. Most of the patients (34.1%) were admitted in the winter season. In multivariate analysis, there was a significantly higher incidence of PPM implantations among men during the winter season as compared to the fall season (Adjusted IRR [Incidence Rate-Ratio] 1.40, 95% CI 1.05;1.88; pConclusion: In the present analysis the incidence of PPM implantations due to AV block was higher among men during the winter season and correlated with high influenza illness rates. Further prospective and larger studies are required to assess these findings.

BackgroundThe COVID-19 pandemic presented new challenges for the existing respiratory surveillance systems, and adaptations were implemented. Systematic assessment of the syndromic and sentinel surveillance platforms during the pandemic is essential for understanding the value of each platform in the context of an emerging pathogen with rapid global spread.AimWe aimed to evaluate systematically the performance of various respiratory syndromic surveillance platforms and the sentinel surveillance system in Israel from 1 January to 31 December 2020.MethodsWe compared the 2020 syndromic surveillance trends to those of the previous 3 years, using Poisson regression adjusted for overdispersion. To assess the performance of the sentinel clinic system as compared with the national SARS-CoV-2 repository, a cubic spline with 7 knots and 95% confidence intervals were applied to the sentinel network's weekly percentage of positive SARS-CoV-2 cases.ResultsSyndromic surveillance trends changed substantially during 2020, with a statistically significant reduction in the rates of visits to physicians and emergency departments to below previous years' levels. Morbidity patterns of the syndromic surveillance platforms were inconsistent with the progress of the pandemic, while the sentinel surveillance platform was found to reflect the national circulation of SARS-CoV-2 in the population.ConclusionOur findings reveal the robustness of the sentinel clinics platform for the surveillance of the main respiratory viruses during the pandemic and possibly beyond. The robustness of the sentinel clinics platform during 2020 supports its use in locations with insufficient resources for widespread testing of respiratory viruses.

Guidelines for pandemic preparedness emphasize the role of sentinel and syndromic surveillance in monitoring pandemic spread.To examine advantages and obstacles of utilizing a sentinel influenza surveillance system to monitor community severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activity based on Israel's experience from mid-March to mid-May 2020.Several modifications were applied to the influenza surveillance system. The clinical component relied mainly on pneumonia and upper respiratory infection (URI) consultations with primary care physicians as well as visits to emergency departments (ED) due to pneumonia. The virological data were based on nasopharyngeal swabs obtained from symptomatic patients who visited outpatient clinics.By week 12 of the pandemic, the crude and age-specific primary physician consultation rates due to URI and pneumonia declined below the expected level, reaching nadir that lasted from week 15 until week 20. Similarly, ED visits due to pneumonia were significantly lower than expected from weeks 14 and 15 to week 20. The virological surveillance started on week 13 with 6/253 of the swabs (2.3%) positive for SARS-CoV-2. There was a peak of 13/225 positive swabs on week 145.8%. During weeks 17-20, none of the swabs (47-97 per week) were positive for SARS-CoV-2. This trend was similar to national data.The virological component of the surveillance system showed the SARS-CoV-2 community spread, but had low sensitivity when virus activity was low. The clinical component, however, had no yield. Sentinel surveillance can assist in monitoring future novel pandemics and should be augmented in revised preparedness plans.

BackgroundCommunication between health authorities and healthcare providers is an essential element of the response to public health emergencies. Although call centers can facilitate such communication, no published reports describing their outcomes exist. In advance of the expected COVID-19 outbreak in Israel, the Israel Center for Disease Control established a call center dedicated to queries from healthcare professionals.MethodsThe call center operated from February 5, 2020 (week 6) to May 14, 2020 (week 20). Data on calls received, including date and time, caller characteristics, questions and responses were recorded in a database designed for this purpose. The volume, sources and content of queries were analyzed.ResultsIn 15 weeks of operation, the call center responded to 6623 calls. The daily number of calls ranged from 1 to 371 (mean 79.8, median 40), peaking on week 12, 2 weeks prior to a peak in new COVID-19 cases. Callers were predominantly physicians (62.4%), nurses (18.7%) and administrators (4.4%). Most worked in primary care clinics (74.2%) or hospitals (8.7%). Among physicians, 42.3% were family physicians or internists, and 10.0% were pediatricians.The issues most commonly addressed were home quarantine (21.6%), criteria for suspected cases (20.6%), and SARS-CoV2 testing (14.1%). Twenty-five percent of questions involved requests for clarifications of MOH guidelines regarding travel restrictions, clinic management, triage of symptomatic patients, routine medical and dental care, recommended precautions for health care workers with preexisting medical conditions, and other matters. A total of 119 queries were not resolved on the basis of existing guidelines and were referred to MOH headquarters.ConclusionsThis is the first report of a call center established to serve the needs of healthcare providers seeking guidance on COVID-19 management, and to facilitate communication of providers’ concerns to the central health authority. Our work indicates that a central call center for healthcare providers can facilitate the development, implementation and amendment of guidelines and should be an integral element of the early response to public health emergencies. Real-time analysis of the call data may reveal important trends requiring prompt attention.

Background The 2017–2018 influenza season in Israel was characterized by the predominance of influenza B Yamagata, with a lesser circulation of influenza A(H1N1)pdm09 and influenza A(H3N2). We estimated vaccine effectiveness (VE) of the inactivated influenza vaccine which was selected for use that season. Methods End-of-season VE and 95% confidence intervals (CI) against laboratory-confirmed influenza-like illness (ILI) were estimated by means of the test-negative design. Age-specific VE analysis was carried out using a moving age interval. Results Specimen were obtained from 1,453 community ILI patients; 610 (42.0%) were influenza-positive, among which 69.7% were B, 17.2% A(H1N1)pdm09 and 13.4% A(H3N2). A 98.6% of molecularly characterized influenza B belonged to the Yamagata lineage. Of the sampled individuals, 1320 were suitable for VE analysis. Of those vaccinated, 90.6% received the inactivated trivalent influenza vaccine (TIV) containing a Victoria lineage influenza B-like virus. VE against influenza A differed by age, with the highest VE of 72.9% (95%CI 31.9–89.2%) observed in children 0.5–14 years old, while all ages VE was 46.6% (95%CI 10.4–68.2%). All ages VE against influenza B was 23.2% (95%CI −10.1–46.4%) with age-specific analysis showing non-significant VE estimates. Utilizing a moving age interval of 15 years, afforded a detailed age-specific insight into influenza VE against the influenza viruses circulating during the 2017–2018 season. Conclusions The moderate-high 2017–2018 influenza A VE among children and adolescents, supports seasonal influenza vaccination at a young age. The low VE against influenza B in Israel, is most likely the result of influenza B/TIV-mismatch.

BACKGROUND In December 2010, the pentavalent rotavirus vaccine (RotaTeq) was added to the national immunization program in Israel. The study aim was to examine national reductions in all-cause acute gastroenteritis (AGE) and rotavirus gastroenteritis (RVGE) hospitalizations among children aged 0-59 months following the introduction of universal rotavirus immunization in Israel. METHODS We extracted data from the Israel National Hospital Discharge Database. Hospitalization rates were calculated by dividing the annual number of all-cause AGE and RVGE hospitalizations by the number of children aged 0-59 months residing Israel. To assess rate reductions, we compared the mean hospitalization rate for the pre-vaccine years (2002-2008) with that for the universal vaccination years (2011-2017). Interrupted time-series analyses were undertaken. During 2008-2010 rotavirus vaccines were partially available. RESULTS A total of 131,116 AGE hospitalizations were reported, of which 13,111 (10.0%) were coded as RVGE hospitalizations. The average annual all-cause AGE hospitalization rate during the pre-vaccine period was 147.9 (95% CI 146.7-149.0) per 10,000 children aged 0-59 months, and declined by 38.7-53.0% during the universal vaccination years. The average annual pre-vaccine RVGE hospitalization rate was 16.9 (95% CI 16.5-17.3) per 10,000 children, and declined by 89.1% during 2016-2017. Findings from interrupted time-series analyses showed significant impact of introducing universal rotavirus immunization on the declines of all-cause AGE and RVGE hospitalizations rates. A multivariable Autoregressive Integrated Moving Average model showed that the variable "immunization period" was a significant predictor of RVGE hospitalizations (t = 7.3, p

Until recently, children and adolescents were not eligible for COVID-19 vaccination. They may have been a considerable source of SARS-CoV-2 spread. We evaluated SARS-CoV-2 IgG antibody seroprevalence in Israeli children aged 0–15 years from January 2020 to March 2021. Seropositivity was 1.8–5.5 times higher than COVID-19 incidence rates based on PCR testing. We found that SARS-CoV-2 infection among children is more prevalent than previously thought and emphasise the importance of seroprevalence studies to accurately estimate exposure.

In Israel, the BNT162b2 vaccine against severe acute respiratory syndrome coronavirus 2 was approved for use in adolescents in June 2021, shortly before an outbreak of B.1.617.2 (Delta) variant-dominant infection. We evaluated short-term vaccine effectiveness and found the vaccine to be highly effective among this population in this setting.

Several countries have recently transitioned from the trivalent inactivated influenza vaccine (TIV) to the quadrivalent inactivated influenza vaccine (QIV) in order to outweigh influenza B vaccine-mismatch. However, few studies thus far evaluated its benefits versus the TIV in a systematic manner. Our objective was to compare the QIV VE with lineage-mismatched TIV VE.We estimated the 2015-2016, 2017-2018, 2019-2020 end-of season influenza B VE against laboratory-confirmed influenza-like illness (ILI) among community patients, using the test-negative design. VE was estimated for pre-determined age groups and for moving age intervals of 15 years.Since 2011-2012 season, alternate seasons in Israel were dominated by influenza B circulation. Compared with the lineage-mismatched TIV used during the 2015-2016 and 2017-2018 seasons, the 2019-2020 QIV showed the highest all-ages VE, with VE estimates of 56.9 (95% CI 30.1 to 73.4), 16.5 (95% CI -22.5 to 43.1) and -25.8 (95% CI -85.3 to 14.6) for the 2019-2020, 2017-2018 and 2015-2016 seasons, respectively. The 2019-2020 VE point estimated were the highest for the 0.5-4, 5-17 and 18-44 years age groups and for more 15-year age intervals as compared to the other seasons.Our results support the rapid transition from the TIV to the QIV.

AIM Early-onset neonatal sepsis (EOS) may lead to significant morbidity and mortality, yet the recommended antimicrobials have not changed for many years. We aimed to optimise EOS treatment by examining EOS pathogens, resistance rates and resistance risk factors. METHODS A retrospective, nationwide cohort study analysing 2010-2015 EOS data in Israel. RESULTS The 21 participating centres constitute 92% of the total birth cohort (around 180 000 live births/year). Of 549 EOS neonates (0.57/1000 live births), 306 (56%) and 243 (44%) were full-term and preterm, respectively (0.35 vs. 2.94 per/1000 live births). Gram-negative pathogens predominated, especially in preterms. Escherichia coli and Streptococcus agalactiae were most common pathogens (0.2 and 0.19 per 1000 live births, respectively). In 277 Gram-negatives, 16%, 14%, 8% and 3% were gentamicin-resistant, extended-spectrum beta-lactamase (ESBL)-positive, gentamicin-resistant and ESBL-positive, and amikacin-resistant, respectively; preterms had higher resistance rates. No risk factors for antimicrobial resistance were identified. Mortality was reported in 21% of Gram-negative EOS versus 7% of Gram-positive EOS [OR 3.4 (95% CI 1.8-6.2), p

Following low incidence of respiratory syncytial virus (RSV) infections in 2020 during the COVID-19 pandemic, we noted a resurgence in hospitalised children in spring/summer 2021 following relaxation of public health measures. We compared this outbreak to previous autumn/winter seasons. We found higher weekly case numbers and incidence rates, more cases from urban neighbourhoods with lower socioeconomic status, and similar clinical presentation and severity. Public health implications include the re-evaluation of palivizumab administration and the need for surge capacity planning.

Influenza viruses and respiratory syncytial virus (RSV) are respiratory viruses that primarily circulate worldwide during the autumn and winter seasons. Seasonal surveillance has shown that RSV infection generally precedes influenza. However, in the last four winter seasons (2016&ndash, 2020) an overlap of the morbidity peaks of both viruses was observed in Israel, and was paralleled by significantly lower RSV infection rates. To investigate whether the influenza A virus inhibits RSV, human cervical carcinoma (HEp2) cells or mice were co-infected with influenza A and RSV. Influenza A inhibited RSV growth, both in vitro and in vivo. Mass spectrometry analysis of mouse lungs infected with influenza A identified a two-wave pattern of protein expression upregulation, which included members of the interferon-induced protein with the tetratricopeptide (IFITs) family. Interestingly, in the second wave, influenza A viruses were no longer detectable in mouse lungs. In addition, knockdown and overexpression of IFITs in HEp2 cells affected RSV multiplicity. In conclusion, influenza A infection inhibits RSV infectivity via upregulation of IFIT proteins in a two-wave modality. Understanding the immune system involvement in the interaction between influenza A and RSV viruses will contribute to the development of future treatment strategies against these viruses.

Influenza viruses and respiratory syncytial virus (RSV) are respiratory viruses that primarily circulate worldwide during the autumn and winter seasons. Seasonal surveillance shows that RSV infection generally precedes influenza. However, in the last four winter seasons (2016-2020) an overlap of the morbidity peaks of both viruses was observed in Israel, and was paralleled by significantly lower RSV infection rates. To investigate whether the influenza virus inhibits RSV we performed coinfection of Human cervical carcinoma (HEp2) cells or mice with influenza and RSV and we observed that the influenza inhibited RSV growth, both in vitro and in vivo. Mass spectrometry analysis of mouse lungs infected with influenza identified a two-wave pattern of protein expression upregulation, which included members of the interferon-induced protein with tetratricopeptide (IFITs) family. Interestingly, in the second peak of upregulation, influenza viruses were no longer detectable in mouse lungs. We also observed that knockdown and overexpression of IFITs in HEp2 cells affected RSV multiplicity. In conclusion, influenza infection inhibits RSV infectivity via upregulation of IFIT proteins in a two-wave modality. Understanding of the interaction between influenza and RSV viruses and immune system involvement will contribute to the development and optimization of future treatment strategies against these viruses.Author SummaryRespiratory syncytial virus (RSV) and influenza viruses are both respiratory viruses associated with morbidity and mortality worldwide. RSV is usually detected in October, with a clear peak in December, whereas influenza virus arrives in November and peaks in January. In the last four seasons, influenza infection overlapped with that of RSV in Israel, which resulted in decreased morbidity of RSV suggesting that influenza virus inhibits RSV infection. To identify the mechanism responsible for the influenza inhibition of RSV we performed experiments in culture and in mice. We observed that influenza infection results in two wave modality of inhibition of RSV infection. Using mass spectrometry perfornmed on lungs from infected mice we show that influenza infection induces the expression of (IFIT) family of proteins which also showed a two-wave modality. Using knockdown and overexpression experiments we showed that indeed the IFTIs inhibits RSV infection. Our study provides new insights on the interaction between influenza and RSV viruses and immune system involvement and contribute to the development of future treatment strategies against these viruses.

Background: Influenza A (H3N2) clade 3C.3a was the predominant influenza virus in Israel throughout the 2018-2019 season, constituting a drift from the influenza A (H3N2) vaccine. We estimated the end-of season vaccine effectiveness (VE) by age, among community patients with influenza-like illness (ILI), considering the hemagglutinin (HA) gene mutations and amino acid substitutions of influenza A (H3N2) viruses detected. Methods: Nose-throat samples were analyzed for the presence of influenza virus, type/subtype, and HA gene sequence. HA gene sequences and amino acid substitutions were compared to the influenza A/Singapore/INFIMH-16-0019/2016 (H3N2)-like 2018-2019 vaccine virus, and a phylogenetic tree was generated. Influenza VE against influenza A (H3N2) was estimated using the test-negative design. VE was estimated by age group and by 15 year moving age intervals. Results: In total, 90% of the influenza A (H3N2) viruses belonged to the 3C.3a clade, constituting a unique situation in the northern hemisphere. Adjusted all-age influenza A (H3N2) VE was −3.5% (95% CI: −51.2 to 29.1). Although adjusted VEs were very low among infants, children, and young adults, a VE of 45% (95% CI: −19.2 to 74.6) was estimated among adults aged ≥45 years old. Conclusions: The higher VE point estimates among older adults may be related to previous exposure to similar influenza viruses.

Additional file 4: Supplemental Figure S1. Flow diagram describing the management of calls made to the ICDC call center.

Additional file 1: Supplemental Table S1. Timeline of events and guidelines related to the national response to COVID-19.

Additional file 3: Supplemental Table S3. The most common calls content in each call category.

Additional file 2: Supplemental Table S2. Categories of questions raised by callers to the ICDC call center (N=6,933).

While infection with influenza A viruses has been extensively investigated, infections with influenza B viruses which are commonly categorized into the highly homologous Victoria and Yamagata lineages, are less studied, despite their considerable virulence. Here we used RT-PCR assays, hemagglutination inhibition assays and antibody titers to determine the levels of influenza B infection. We report of high influenza B Victoria virus prevalence in the 2015–16 winter season in Israel, affecting approximately half of the Israeli population. We further show that the Victoria B virus infected individuals of all ages and that it was present in the country throughout the entire winter season. The vaccine however included the inappropriate Yamagata virus. We propose that a quadrivalent vaccine, that includes both Yamagata and Victoria lineages, should be considered for future influenza vaccination.

Objectives West Nile Virus (WNV) is endemic in Israel and was responsible for several outbreaks in the past 16 years. The aim of the present study was to investigate the spatial distribution of WNV acute infections from an outbreak that occurred in 2015 in Israel and report the molecular and geographic characterization of WNV isolates from human cases and mosquito pools obtained during this outbreak. Methods Using a geographical layer comprising 51 continuous areas of Israel, the number of WNV infection cases per 100 000 people in each area and the locations of WNV-infected mosquitoes in 2015 were analysed. Sequencing and phylogenetic analyses followed by geographic localization were performed on 13 WNV human isolates and 19 WNV-infected mosquito pools. Results Substantial geographical variation in the prevalence of acute WNV in patients in Israel was found and an overall correlation with WNV-infected mosquitoes. All human patients sequenced were infected only with the Mediterranean subtype of WNV Lineage 1 and resided primarily in the coastal regions in central Israel. In contrast, mosquitoes were infected with both the Mediterranean and Eastern European subtypes of WNV lineage 1; however, only the Mediterranean subtype was found in mosquitoes from the coastal region in central Israel. Conclusion These results demonstrate differential geographic dispersion in Israel of the two WNV subtypes and may also point to a differential pattern of human infections. As a geographical bridge between Europe, Asia and Africa, analysis of WNV circulation in humans and mosquitoes in Israel provides information relevant to WNV infections in Eurasia.

Background The 2016-2017 influenza season in Israel was dominated by the circulation of influenza A(H3N2). Influenza vaccine is recommended for the entire population in Israel aged >6 months. The inactivated influenza vaccine was chosen for use this season. Methods We estimated the 2016-2017 end-of-season influenza vaccine effectiveness (VE) in preventing influenza-like illness due to influenza A(H3N2), using the test-negative design. Age-specific VE was estimated using a moving age window and weekly analysis. Results During the 2016-2017 season, 1267 samples were collected; 467 (36.9%) were positive for influenza, with 97.9% A(H3N2), 0.2% A(H1N1)pdm09, and 1.9% B. A total of 1088 individuals were found eligible to be included in VE assessment. All vaccinated individuals included in the VE assessment received the inactivated influenza vaccine. Adjusted VE against influenza A(H3N2) was 29.0% (95% confidence interval [CI], 0.3%-49.5%). Age group-specific adjusted VE was 69.2% (95% CI, 19.4%-88.3%) for children aged 5-17 years and 58.8% (95% CI, .8%-82.9%) for adults aged 45-64 years. Other age groups demonstrated lower VE estimates that were not statistically significant. Adjusted VE estimates using a moving window of 15 years and weekly VE analyses provided a more defined understanding of age-specific VE during the 2016-2017 season. Conclusions Estimating VE using a moving age window as well as weekly VE analysis may provide more detailed information regarding the relationship between VE and age.

BACKGROUND Influenza-related morbidity impacts healthcare systems, including hospitals. OBJECTIVE To obtain a quantitative assessment of hospitalization burden in pediatric and internal medicine departments during influenza seasons compared with the summer months in Israel. METHODS Data on pediatric and internal medicine hospitalized patients in general hospitals in Israel during the influenza seasons between 2005 and 2013 were analyzed for rate of hospitalizations, rate of hospitalization days, hospital length of stay (LOS), and bed occupancy and compared with the summer months. Data were analyzed for hospitalizations for all diagnoses, diagnoses of respiratory or cardiovascular disease (ICD9 390-519), and influenza or pneumonia (ICD9480-487), with data stratified by age. The 2009-2010 pandemic influenza season was excluded. RESULTS Rates of monthly hospitalizations and hospitalization days for all diagnoses were 4.8% and 8% higher, respectively, during influenza seasons as compared with the summers. The mean LOS per hospitalization for all diagnoses demonstrated a small increase during influenza seasons as compared with summer seasons. The excess hospitalizations and hospitalization days were especially noticed for the age groups under 1 year, 1-4 years, and 85 years and older. The differences were severalfold higher for patients with a diagnosis of respiratory or cardiovascular disease and influenza or pneumonia. Bed occupancy was higher during influenza seasons compared with the summer, particularly in pediatric departments. CONCLUSIONS Hospital burden in pediatric and internal medicine departments during influenza seasons in Israel was associated with age and diagnosis. These results are important for optimal preparedness for influenza seasons.

Highlights • A(H3N2) dominated the early stages of the 2016–2017 influenza season. • 36% of hospitalized infected patients received the influenza vaccine. • Circulating A(H3N2) viruses were different from the vaccine strain., Background Influenza vaccine composition is reevaluated each year due to the frequency and accumulation of genetic changes that influenza viruses undergo. The beginning of the 2016–2017 influenza surveillance period in Israel has been marked by the dominance of influenza A(H3N2). Objectives To evaluate the type, subtype, genetic evolution and amino acid substitutions of influenza A(H3N2) viruses detected among community patients with influenza-like illness (ILI) and hospitalized patients with respiratory illness in the first weeks of the 2016–2017 influenza season. Study design Respiratory samples from community patients with influenza-like illness and from hospitalized patients underwent identification, subtyping and molecular characterization. Hemagglutinin sequences were compared to the vaccine strain, phylogenetic tree was created, and amino acid substitutions were determined. Results Influenza A(H3N2) predominated during the early stages of the 2016–2017 influenza season. Noticeably, approximately 20% of community patients and 36% of hospitalized patients, positive for influenza3), received the 2016–2017 influenza vaccine. The influenza A(H3N2) viruses demonstrated genetic divergence from the vaccine strain into three separate subgroups within the 3C.2a clade. One resembled the new 3C.2a1 subclade, one resembled the recently proposed 3C.2a2 subclade and the other was not previously described. Diversity was observed within each subgroup, in terms of additional amino acid substitutions. Conclusions Characterization of the 2016–2017 A(H3N2) influenza viruses is imperative for determining the future influenza vaccine composition.

Background Influenza A and B viruses co-infections are rare events and mainly occurred in immunocompromised patients. Objectives In this study we report an unusually high occurrence of influenza A (H1N1)pdm 2009 and influenza B virus co-infections during the epidemic year 2015–2016. Study design Nasopharyngeal swabs were collected from 1919 patients visiting 26 outpatient clinics distributed throughout Israel and presenting with influenza-like illness. In addition, hospitalized patient tested for influenza viruses were also included in the study. Patients samples collected between October 2015 and April 2016 were tested for the presence of influenza viruses by real-time PCR. Results Of the 1919 patient samples tested, 11 (0.6%) were co-infected with both influenza A(H1N1)pdm 2009 and influenza B/Victoria viruses. Similar observation was noted in four hospitalized patients during the same period. Patients at ages 1–72 years, and their clinical symptoms were similar to that of patients infected with either influenza A or B viruses. Of all patients, only one hospitalized patient was immunocompromised. In conclusion : Co-infection of influenza A(H1N1)pdm 2009 and influenza B viruses is an increasingly recognized phenomenon. This co-infection can occur not only in immunocompromised individuals, but also in immunocompetent patients. Although co-infection appears to be a rare event, it may still play a role in the epidemiology, pathogenicity and evolution of influenza viruses.

// Nehemya Friedman 1, 2, * , Yaron Drori 1, 2, * , Rakefet Pando 3 , Aharona Glatman-Freedman 3, 4 , Hanna Sefty 3 , Ravit Bassal 3 , Yaniv Stein 3 , Tamy Shohat 2, 3 , Ella Mendelson 1, 2 , Musa Hindiyeh 1, 2 , Michal Mandelboim 1, 2 1 Central Virology Laboratory, Ministry of Health, Chaim Sheba Medical Center, Ramat-Gan, Israel 2 Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel 3 The Israel Center for Disease Control, Israel Ministry of Health, Tel-Hashomer, Israel 4 Departments of Pediatrics and Family and Community Medicine, Valhalla, New York, USA * These authors contributed equally to this work Correspondence to: Michal Mandelboim, email: michalman@sheba.health.gov.il Keywords: influenza A, H1N1, vaccine, Clade 6B Received: November 22, 2016 Accepted: March 14, 2017 Published: March 22, 2017 ABSTRACT The last influenza pandemic, caused by the swine A(H1N1)pdm09 influenza virus, began in North America at 2009. Since then, the World Health Organization (WHO) recommended integration of the swine-based virus A/California/07/2009 strain in yearly vaccinations. Yet, infections with A(H1N1)pdm09 have continued in subsequent years. The reasons for this are currently unknown. During the 2015–2016 influenza season, we noted an increased prevalence of A(H1N1)pdm09 influenza virus infection in Israel. Our phylogenetic analysis indicated that the circulating A(H1N1)pdm09 strains belonged to 6B.1 and 6B.2 clades and differed from the vaccinating strain, with approximately 18 amino acid differences found between the circulating strains and the immunizing A/California/07/2009 strain. Hemmaglutination inhibition (HI) assays demonstrated higher antibodies titer against the A/California/07/2009 vaccinating strain as compared to the circulating Israeli strains. We thus suggest that the current vaccination was not sufficiently effective and propose inclusion of the current circulating A(H1N1)pdm09 influenza viruses in the annual vaccine composition.

Respiratory Syncytial Virus (RSV) is a known cause of morbidity among young children, while RSV-related disease in the elderly is not fully recognized. Several RSV candidate vaccines for infants, pregnant women and adults are under development. We aimed to estimate nationwide age-specific hospitalizations and seasonal trends, to help determine the optimal age for vaccination.Hospitalizations with a primary RSV-related diagnoses were retrieved from the National Hospital Database for the years 2000-2017. Data were analyzed by year, month and age group to determine hospitalization rates and seasonal trends.During the analysis period, 39,156 hospitalizations received primary RSV-related ICD-9 diagnostic codes. The highest mean yearly hospitalization rate occurred among infants1 year of life (1,218.4 per 100,000). Within the first year of life, the highest mean yearly hospitalization rate was observed in the second month of life (3,541.5 hospitalizations per 100,000). Hospitalization rates for individuals ≥5 years old increased during the study period, primarily among patients ≥65 years of age, reaching hospitalization rate of 9 per 100,000 in 2017. A clear seasonal pattern was observed.An effective vaccine for infants and pregnant women has the potential to reduce hospitalizations burden. RSV-related hospitalizations burden among adults requires additional research.

Background Vaccinating children against influenza has shown both direct and indirect beneficial effects. However, despite being offered free of charge, childhood influenza vaccine coverage in Israel has been low. Our objective was to evaluate the factors associated with childhood influenza vaccination in Israel. Methods A cross-sectional language-specific telephone survey was conducted among adults 18 years or older, to examine childhood influenza vaccination practices and their associations with socio-demographic and relevant health variables. We further explored the reasons for these practices among parents. Multivariate logistic regression was used to identify factors associated with childhood influenza vaccine acceptance. Results Of a total of 6518 individuals contacted by mobile phone, 1165 eligible parents, ≥18 years old with children 1–18 years of age, were interviewed, and 1040 of them completed the survey successfully. Overall, factors associated with childhood influenza vaccination were younger child’s age, influenza vaccination of other family members and belonging to the Arab population group. No association was found between childhood influenza vaccination and routine childhood vaccine uptake. Several of the parents’ reasons for vaccine acceptance - preventing influenza or its transmission, awareness regarding the need for influenza vaccination and receipt of invitation to get vaccinated - differed significantly between Jewish and Arab parents. Several reasons reported by parents for not vaccinating children against influenza, indicated a likelihood to accept influenza vaccine outreach efforts. Such reasons were reported by 27.5% of Jewish parents and 37.5% of Arab parents. Conclusions We found that certain demographic factors were associated with childhood influenza vaccination in Israel. Several reasons described by the parent for not vaccinating their children indicate that outreach efforts are likely to increase childhood influenza vaccination. Addressing population group-specific needs is recommended to optimize the success of influenza vaccine outreach efforts.

Respiratory virus infections are very common. Such infections impose an enormous economic burden and occasionally lead to death. Furthermore, every few decades, respiratory virus pandemics emerge, putting the entire world population at risk. Thus, there is an urgent need to quickly and precisely identify the infecting agent in a clinical setting. However, in many patients with influenza-like symptoms (ILS) the identity of the underlying pathogen remains unknown. In addition, it takes time and effort to individually identify the virus responsible for the ILS. Here, we present a new next-generation sequencing (NGS)-based method that enables rapid and robust identification of pathogens in a pool of clinical samples without the need for specific primers. The method is aimed at rapidly uncovering a potentially common pathogen affecting many samples with an unidentified source of disease.

The quadrivalent influenza vaccine (QIV) contains two influenza B antigens (one of each B lineage), while the trivalent vaccine (TIV) contains solely one. As a result, a mismatch between the circulating B lineage and the lineage in the TIV occurs frequently. We aimed to compare the frequency of clinically significant outcomes in a large cohort of vaccinees receiving either TIV or QIV.Historical cohort study of all inactivated influenza vaccinees (aged 3 years and older) in a Health Maintenance Organization insuring 1.2 million individuals, over two influenza seasons in which both vaccines were provided non-selectively. Primary outcome was hospital admissions during the influenza season. Multivariate analysis was performed using logistic regression to adjust for relevant covariates.Our cohort included 150 518 and 168 296 vaccinees in the first (S1) and second season (S2), respectively. The two influenza seasons were characterized by high Influenza B activity. Of those vaccinated with QIV, 2074 of 49 726 (4.2%) and 6563 of 121 741 (5.4%) were hospitalized compared with 7378 of 100 792 (7.3%) and 3372 of 46 555 (7.2%) of those vaccinated with TIV (S1 and S2, respectively). After multivariate analysis adjusting for several covariates (gender, age, socioeconomic status, chronic morbidity, timing of vaccination), compared with TIV recipients, QIV vaccinees had lower odds for hospitalization (OR = 0.92, 95% CI 0.87-0.98 and OR = 0.89, 95% CI 0.85-0.93) or emergency department visit (OR = 0.91, 95% CI 0.87-0.95 and OR = 0.84, 95% CI 0.81-0.87) in S1 and S2, respectively (p 0.001). Lower odds of mortality and influenza-like illness were also observed in S2 (OR = 0.61, 95% CI 0.50-0.75 and OR = 0.92, 95% CI 0.90-0.95, respectively).In seasons with relatively high influenza B activity, QIV appeared more protective than TIV in Israel.

Respiratory syncytial virus (RSV)-related bronchiolitis is a common cause of morbidity in young infants. The recommendations for its passive prevention by palivizumab are currently under intensive debate.To elucidate the optimal prevention strategy by studying the morbidity of RSV disease under the current recommendations for palivizumab prophylaxis in Israel.We collected demographic and clinical data of all children hospitalized with microbiologically confirmed RSV bronchiolitis during 2015-2016 at Schneider Children's Medical Center. The seasonality of RSV disease was also studied for the period 2010-2017 in sentinel clinics scattered throughout Israel.Of the 426 hospitalized children, 106 (25%) had underlying diseases but were not eligible for palivizumab prophylaxis according to the current criteria in Israel. Their course was severe, with a mean hospital stay of 6.7 days and a 12% admission rate to the pediatric intensive care unit (PICU). Palivizumab-eligible children who did not receive the prophylaxis before hospitalization had the most severe course, with 22% admitted to the PICU. More children were diagnosed with RSV disease in October than in March among both hospitalized and ambulatory children; 44% of the palivizumab-eligible hospitalized children were admitted in the last 2 weeks of October, before 1 November which is the recommended date for starting palivizumab administration in Israel.According to the results of the present study we suggest advancing RSV prophylaxis in Israel from 1 November to mid-October. The precise palivizumab-eligible categories should be reconsidered.

Additional file 3: Table S3. Influenza vaccination of index child in the past influenza season according to examined variables (N vaccinated =306).

Background The Study of Healthcare Personnel with Influenza and other Respiratory Viruses in Israel (SHIRI) prospectively follows a cohort of healthcare personnel (HCP) in two hospitals in Israel. SHIRI will describe the frequency of influenza virus infections among HCP, identify predictors of vaccine acceptance, examine how repeated influenza vaccination may modify immunogenicity, and evaluate influenza vaccine effectiveness in preventing influenza illness and missed work. Methods Cohort enrollment began in October, 2016; a second year of the study and a second wave of cohort enrollment began in June 2017. The study will run for at least 3 years and will follow approximately 2000 HCP (who are both employees and members of Clalit Health Services [CHS]) with routine direct patient contact. Eligible HCP are recruited using a stratified sampling strategy. After informed consent, participants complete a brief enrollment survey with questions about occupational responsibilities and knowledge, attitudes, and practices about influenza vaccines. Blood samples are collected at enrollment and at the end of influenza season; HCP who choose to be vaccinated contribute additional blood one month after vaccination. During the influenza season, participants receive twice-weekly short message service (SMS) messages asking them if they have acute respiratory illness or febrile illness (ARFI) symptoms. Ill participants receive follow-up SMS messages to confirm illness symptoms and duration and are asked to self-collect a nasal swab. Information on socio-economic characteristics, current and past medical conditions, medical care utilization and vaccination history is extracted from the CHS database. Information about missed work due to illness is obtained by self-report and from employee records. Respiratory specimens from self-collected nasal swabs are tested for influenza A and B viruses, respiratory syncytial virus, human metapneumovirus, and coronaviruses using validated multiplex quantitative real-time reverse transcription polymerase chain reaction assays. The hemagglutination inhibition assay will be used to detect the presence of neutralizing influenza antibodies in serum. Discussion SHIRI will expand our knowledge of the burden of respiratory viral infections among HCP and the effectiveness of current and repeated annual influenza vaccination in preventing influenza illness, medical utilization, and missed workdays among HCP who are in direct contact with patients. Trial registration NCT03331991. Registered on November 6, 2017. Electronic supplementary material The online version of this article (10.1186/s12879-018-3444-7) contains supplementary material, which is available to authorized users.