The Concordance between Mumps and Rubella Sero-Positivity among the Israeli Population in 2015.

Mumps and rubella are vaccine-preventable viral diseases through the measles-mumps-rubella-varicella (MMRV) vaccine, administered at 12 months and again at 6 years. We assessed the sero-prevalence of mumps and rubella, identified factors associated with sero-negativity, and evaluated concordance between mumps and rubella sero-positivity. A national cross-sectional sero-survey was conducted on samples collected in 2015 by the Israel National Sera Bank. Samples were tested for mumps and rubella IgG antibodies using an enzyme-linked immunosorbent assay. Of 3131 samples tested for mumps IgG, 84.8% (95%CI: 83.5-86.0%) were sero-positive. Sero-negativity for mumps was significantly associated with age (high odds ratios observed in infants younger than 4 years and 20-29 years old subjects). Of 3169 samples tested for rubella IgG antibodies, 95.2% (95%CI: 94.4-95.9%) were sero-positive. Rubella sero-negativity was significantly associated with age (high odds ratios observed in children younger than 4 years old and adults older than 30 years), males, Jews, and others. Concordant sero-positivity for both mumps and rubella viruses was observed in 83.9% of the tested samples. The Israeli population was sufficiently protected against rubella but not against mumps. Since both components are administered in the MMRV vaccine simultaneously, the mumps component has a lower uptake than rubella and quicker waning.

The impact of SARS-CoV-2 on respiratory syndromic and sentinel surveillance in Israel, 2020: a new perspective on established systems.

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.

Lineage-matched versus mismatched influenza B vaccine effectiveness following seasons of marginal influenza B circulation.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Our results support the rapid transition from the TIV to the QIV.

Diversity in the Circulation of Influenza A(H3N2) Viruses in the Northern Hemisphere in the 2018-19 Season.

While vaccination is considered the most effective means to prevent influenza infection, its seasonal effectiveness varies, depending on the circulating influenza strains. Here, we characterized the circulation of influenza strains in October-2018 and March-2019 around the world. For this, we used nasopharyngeal samples collected from outpatient and hospitalized patients in Israel and data reported in ECDC, CDC, and WHO databases. Influenza A(H3N2) was dominant in Israel, while in Europe, Asia, and USA, A(H1N1)pdm09 virus circulated first, and then the A(H3N2) virus also appeared. Phylogenetic analysis indicated that A(H3N2) viruses circulating in Israel belonged to clade-3C.3a, while in Europe, Asia, and USA, A(H3N2) viruses belonged to subclade-3C.2a1, but were later replaced by clade-3C.3a viruses in USA. The vaccine A(H3N2) components of that year, A/Singapore/INFIMH-16-0019/2016-(H3N2)-like-viruses, belonged to clade-3C.2a1. The circulation of different influenza subtypes and clades of A(H3N2) viruses in a single season highlights the need for universal influenza vaccines.

Genomic variation and epidemiology of SARS-CoV-2 importation and early circulation in Israel.

Severe acute respiratory disease coronavirus 2 (SARS-CoV-2) which causes corona virus disease (COVID-19) was first identified in Wuhan, China in December 2019 and has since led to a global pandemic. Importations of SARS-CoV-2 to Israel in late February from multiple countries initiated a rapid outbreak across the country. In this study, SARS-CoV-2 whole genomes were sequenced from 59 imported samples with a recorded country of importation and 101 early circulating samples in February to mid-March 2020 and analyzed to infer clades and mutational patterns with additional sequences identified Israel available in public databases. Recorded importations in February to mid-March, mostly from Europe, led to multiple transmissions in all districts in Israel. Although all SARS-CoV-2 defined clades were imported, clade 20C became the dominating clade in the circulating samples. Identification of novel, frequently altered mutated positions correlating with clade-defining positions provide data for surveillance of this evolving pandemic and spread of specific clades of this virus. SARS-CoV-2 continues to spread and mutate in Israel and across the globe. With economy and travel resuming, surveillance of clades and accumulating mutations is crucial for understanding its evolution and spread patterns and may aid in decision making concerning public health issues.

Seropositivity of measles antibodies in the Israeli population prior to the nationwide 2018 - 2019 outbreak.

Measles vaccine is administered in Israel as part of the routine childhood immunization program, at ages 1 and 6 years. In this study, we assessed seropositivity of the Israeli population against measles before the onset and propagation of the 2018-2019 measles outbreak. From the Israel Center for Disease Control National Serum Bank, 3,164 samples collected during 2015 were tested for measles antibodies. All the tests were performed using Enzyme-Linked Immunosorbent Assay (ELISA) commercial kit (Enzygnost, Anti-Measles Virus/IgG: Behring, Marburg, Germany). The overall seropositivity rate for measles was 90.7%. The seropositivity rate at 6 months and younger was 48.9%, and decreased to 3.8% among infants aged 6-11 months. Seropositivity increased to 90.7% in the 1-4-year age group, and reached 96.1% for 5-9 year-old children. Our results suggest high immunity in the Israeli population against measles virus, but not high enough to prevent outbreaks because of pockets of specific population groups with low immunization coverage. Infants between ages 6 and 11 months and children younger than 2 years had the lowest seropositivity rates being the age groups with the highest attack rates of measles during the epidemic of 2018. Efforts should be aimed at avoiding any delay in vaccination once a child reaches the age of 1 year and improving immunity levels in children aged 1-4 years.

Influenza A Virus Inhibits RSV Infection via a Two-Wave Expression of IFIT Proteins.

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 (2016-2020) 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.

Comprehensive Analyses of SARS-CoV-2 Transmission in a Public Health Virology Laboratory.

SARS-CoV-2 has become a major global concern as of December 2019, particularly affecting healthcare workers. As person-to-person transmission is airborne, crowded closed spaces have high potential for rapid virus spread, especially early in the pandemic when social distancing and mask wearing were not mandatory. This retrospective study thoroughly investigates a small-scale SARS-CoV-2 outbreak in Israel's central virology laboratory (ICVL) in mid-March 2020, in which six staff members and two related family members were infected. Suspicions regarding infection by contaminated surfaces in ICVL facilities were nullified by SARS-CoV-2 negative real time polymerase chain reaction (PCR) of work surfaces swipe tests. Complete SARS-CoV-2 genomes were sequenced and mutation analyses showed inclusion of all samples to clades 20B and 20C, possessing the spike mutation D614G. Phylogenetic analysis clarified transmission events, confirming S1 as having infected at least three other staff members and refuting the association of a staff member's infected spouse with the ICVL transmission cluster. Finally, serology tests exhibited IgG and IgA antibodies in all infected individuals and revealed the occurrence of asymptomatic infections in additional staff members. This study demonstrates the advantages of molecular epidemiology in elucidating transmission events and exemplifies the importance of good laboratory practice, distancing and mask wearing in preventing SARS-CoV-2 spread, specifically in healthcare facilities.

Adenovirus load correlates with respiratory disease severity among hospitalized pediatric patients.

OBJECTIVES: Human adenoviruses (HAdVs) are common pathogens that can cause respiratory, gastrointestinal and other infections. We investigated the correlation between adenovirus viral load in clinical respiratory samples and the respiratory disease severity in pediatric patients. METHODS: Medical records of patients hospitalized in the Sheba Medical Center (SMC) with confirmed adenovirus infection were retrospectively analyzed. The possible correlation between disease severity score and Real time PCR 'cycle threshold' (Ct), a proxy of viral load, was assessed in patients aged 9 years and under. In addition, Ct values of hospitalized versus community-care patient samples, positive for various respiratory viruses including adenovirus, were compared. RESULTS: Adenovirus load in respiratory samples, as measured by Ct values, was found to be negatively correlated with respiratory disease severity in hospitalized pediatric patients aged under 9 years. Moreover, hospitalized patients presented with significantly higher Ct levels for various respiratory viruses as compared to community-care patients. CONCLUSION: In this study we found a correlation between Ct values obtained from adenovirus q-PCR analysis of respiratory clinical samples and disease severity in patients aged 9 years and under. Such finding may serve as a predictor of respiratory disease course in pediatric patients and will be beneficial for the differential diagnosis and treatment of pediatric patients.

Predominance of a Drifted Influenza A (H3N2) Clade and its Association with Age-specific Influenza Vaccine Effectiveness Variations, Influenza Season 2018-2019.

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.

Rhinovirus infections in infants suggest that early detection can prevent unnecessary treatment.

BACKGROUND: Human rhinoviruses (hRV) are small, RNA viruses of the Picornaviridae family, which are divided into three subtypes (A, B, C). hRVs are among the most common causes for acute respiratory illnesses (ARI) involving both the upper and lower respiratory tract. OBJECTIVES: This study aimed to assess the magnitude and characteristics of hRV infections in hospitalized children, aged less than 5 years, hospitalized in Israel during 2011-2012. STUDY DESIGN: The 2503 respiratory samples were subjected to real-time PCR, to detect hRV and other respiratory viruses. Rhinovirus-positive samples were further tested by sequencing to identify the infecting species. RESULTS: Of these 2503 respiratory samples, 422 tested positive for hRV, of them, 243 were from children under 5 years of age (58% of all rhinoviral-positive samples). We also found that among the ARI-associated hospital admissions, 16% were positive for rhinovirus. hRV type A was the most common species. Laboratory data showed monocytosis in 51%, hypercalcemia in 61% and lower respiratory tract involvement in 75% of patients. CONCLUSIONS: We thus recommend including rhinovirus testing as part of the routine testing performed in young children presenting with ARI.

Comparison of the new fully automated extraction platform eMAG to the MagNA PURE 96 and the well-established easyMAG for detection of common human respiratory viruses.

Respiratory viral infections constitute the majority of samples tested in the clinical virology laboratory during the winter season, and are mainly diagnosed using molecular assays, namely real-time PCR (qPCR). Therefore, a high-quality extraction process is critical for successful, reliable and sensitive qPCR results. Here we aimed to evaluate the performance of the newly launched eMAG compared to the fully automated MagNA PURE 96 (Roche, Germany) and to the semi-automated easyMAG (bioMerieux, France) extraction platforms. For this analysis, we assessed and compared the analytic and clinical performance of the three platforms, using 262 archived respiratory samples positive or negative to common viruses regularly examined in our laboratory (influenza A, B, H1N1pdm, Respiratory Syncytial Virus (RSV), human Metapneumovirus (hMPV), parainfluenza-3, adenovirus and negative samples). In addition, quantitated virus controls were used to determine the limit of detection of each extraction method. In all categories tested, eMAG results were comparable to those of the easyMAG and MagNa PURE 96, highly sensitive for all viruses and over 98% clinical specificity and sensitivity for all viruses tested. Together with its high level of automation, the bioMerieux eMAG is a high-quality extraction platform enabling effective molecular analysis and is mostly suitable for medium-sized laboratories.

Effectiveness of influenza vaccine in preventing medically-attended influenza virus infection in primary care, Israel, influenza seasons 2014/15 and 2015/16.

IntroductionInfluenza vaccine is recommended for the entire population in Israel. We assessed influenza vaccine effectiveness (VE) for the 2014/15 and 2015/16 seasons in Israel, for the first time. Methods: Combined nose and throat swab specimens were collected from patients with influenza-like illness (ILI) presenting to sentinel primary care clinics and tested for influenza virus by RT-PCR. VE of the trivalent inactivated vaccine (TIV) was assessed using test-negative case-control design. Results: During the 2014/15 season 1,142 samples were collected; 327 (28.6%) were positive for influenza, 83.8% A(H3N2), 5.8% A(H1N1)pdm09, 9.2% B and 1.2% A un-subtyped. Adjusted VE against all influenza viruses for this influenza season was -4.8% (95% confidence interval (CI): -54.8 to 29.0) and against influenza A(H3N2), it was -15.8% (95% CI: -72.8 to 22.4). For the 2015/16 season, 1,919 samples were collected; 853 (44.4%) were positive for influenza, 43.5% A(H1N1)pdm09, 57% B, 0.7% A(H3N2) and 11 samples positive for both A(H1N1)pdm09 and B. Adjusted VE against all influenza viruses for this influenza season was 8.8% (95% CI: -25.1 to 33.5), against influenza A(H1N1)pdm09, it was 32.3% (95% CI: (-4.3 to 56.1) and against influenza B, it was -2.2% (95% CI: (-47.0 to 29.0). Conclusions: Using samples from patients with ILI visiting sentinel clinics in Israel, we demonstrated the feasibility of influenza VE estimation in Israel.

Exceptional influenza morbidity in summer season of 2017 in Israel may predict the vaccine efficiency in the coming winter.

Influenza infections are the leading cause of respiratory viral infections worldwide, and are mostly common in the winter season. The seasonal influenza vaccine is currently the most effective preventive modality against influenza infection. Immediately following each winter season the World Health Organization (WHO) announces the vaccine composition for the following winter. Unexpectedly, during the summer of 2017, in Israel, we observed in hospitalized patients, an exceptionally high numbers of Influenza positive cases. The majority of the influenza B infections were caused by influenza B/Yamagata lineage, which did not circulate in Israel in the previous winter, and most of the influenza A infections were caused by influenza A/H3N2, a strain similar to the strain that circulated in Israel in the previous winter. We therefore predict that these two viruses will circulate in the coming winter of 2017/18 and that the trivalent vaccine, which includes antigenically different viruses will be inefficient.

Seasonal Influenza Vaccine Effectiveness in Preventing Laboratory-Confirmed Influenza in Primary Care in Israel, 2016-2017 Season: Insights Into Novel Age-Specific Analysis.

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.

Genetic divergence of Influenza A(H3N2) amino acid substitutions mark the beginning of the 2016-2017 winter season in Israel.

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.

A(H1N1)pdm09 influenza infection: vaccine inefficiency.

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.

Influenza A(H1N1)pdm 2009 and influenza B virus co-infection in hospitalized and non-hospitalized patients during the 2015-2016 epidemic season in Israel.

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.

Human enterovirus D68 in clinical and sewage samples in Israel.

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. STUDY DESIGN: Archived clinical respiratory samples from a cohort of 710 hospitalized pediatric patient's (<10years old) with respiratory illness were screened for clade B specific EV-D68 by real-time PCR. The patients were seen at four medical centers covering the entire country between August and November 2014. We also evaluated 49 patient stool samples from 26 AFP cases during 2014 for presence of EV-D68. In addition, RNA from sewage samples collected throughout Israel during the same study period was also tested for EV-D68. Partial VP1 sequencing was performed on all positive samples. RESULTS: Of the 710 clinical samples evaluated, 7 (1%) were positive for EV-D68. Two patients were from the central part of Israel, while the rest was from the southern part. The majority of the patients did not have any underlying disease. Not only that, but, none of the 26 suspected AFP cases had EV-D68 nucleic acid in their stool samples. EV-D68 RNA was detected in 9 out of 93 sewage samples, mainly from Southern Israel. Sequence analysis of EV-D68 VP1 gene from both sewage and clinical samples indicated that the Israeli EV-D68 RNA belonged to Clade B which was genetically similar to 2014 circulating European and North American EV-D68 virus. CONCLUSIONS: EV-D68 circulated in Israel during the 2014 summer-fall season and caused hospitalization of a small percent of the patients with respiratory illness.

Ineffectiveness of the 2014-2015 H3N2 influenza vaccine.

The seasonal influenza vaccine is currently the most effective preventive modality against influenza infection. Nasopharyngeal samples of vaccinated and non-vaccinated patients presenting with Influenza-like-illness (ILI) were collected from over 20 outpatient clinics located in different geographic parts of Israel and were tested for the presence of influenza viruses (influenza A and influenza B). Here we show, that in the 2014-2015 season, the vaccine that included the A/Texas/50/2012 H3N2 virus was ineffective. Significant numbers of individuals vaccinated with the 2014-2015 vaccine, of all ages, were infected with influenza A (H3N2), manifesting similar symptoms as the non-vaccinated group. We further demonstrate that the Israeli circulating influenza A(H3N2) virus was different than that included in the 2014-2015 northern hemisphere vaccine, and that antibodies elicited by this vaccine were significantly less efficient in neutralizing influenza A(H3N2) infection.