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Invasive group A Streptococcus (iGAS) infections have increased in Israel since 2016 as successful lineages have emerged. We report the emergence and outbreak of a multidrug-resistant S. pyogenes emm93.0, sequence type 10, among iGAS infections in Israel since 2017. This type has been observed very rarely in other countries. During this period, emm93.0 was the cause of 116 infections in Israel and became the leading type during 2018. Most of the infections were from bacteremia (75%), and most patients were male (76%). We observed infections across Israel, mainly in adults. Of note, we observed multidrug resistance for clindamycin, tetracycline, and trimethoprim/sulfamethoxazole. Whole-genome sequencing confirmed clonality among geographically disseminated isolates. The local emm93.0 sequence type 10 clone contained a novel genomic island harboring the resistance genes lsa(E), lnu(B), and ant (6)-Ia aph(3′)-III. Further phenotypic and genomic studies are required to determine the prevalence of this resistance element in other iGAS types.

Macrolides have been effective clinical antibiotics for over 70 years. They inhibit protein biosynthesis in bacterial pathogens by narrowing the nascent protein exit tunnel in the ribosome. The macrolide class of natural products consist of a macrolactone ring linked to one or more sugar molecules. Most of the macrolides used currently are semi-synthetic erythromycin derivatives, composed of a 14- or 15-membered macrolactone ring. Rapidly emerging resistance in bacterial pathogens is among the most urgent global health challenges, which render many antibiotics ineffective, including next-generation macrolides. To address this threat and advance a longer-term plan for developing new antibiotics, we demonstrate how 16-membered macrolides overcome erythromycin resistance in clinically isolated Staphylococcus aureus strains. By determining the structures of complexes of the large ribosomal subunit of Deinococcus radiodurans (D50S) with these 16-membered selected macrolides, and performing anti-microbial studies, we identified resistance mechanisms they may overcome. This new information provides important insights toward the rational design of therapeutics that are effective against drug resistant human pathogens.

Invasive meningococcal disease (IMD) is one of the leading causes of bacterial meningitis and septicemia in Israel. The purpose of the study was to describe the IMD in the Tel Aviv District and to identify specific populations who could benefit from vaccine introduction. In the Tel Aviv District, the incidence rates ranged from 0.4 to 1.4 cases per 100,000 population per year during 2007–2017. During the study period, seventy-nine patients (65%) occurred among children younger than four years of age. Eight deaths occurred (7%), most of them among children under the age of 1 year (5 deaths; 15%). A serogroup was identified in 82 isolates. Most of the isolates (69 cases − 84%) belonged to serogroup B (NmB). IMD clustered geographically in the city of Bnei Brak, with a predominantly Ultra-Orthodox Jewish population. It is the youngest and most densely populated city in the district. The overall incidence rates of IMD among children in Bnei Brak were more than seven times higher in children up to nine years, compared to the rest of the district. Specifically for NmB, disease rates were 9.08 times higher in children up to the age of four, and 7.74 times higher in children from five to nine years old in Bnei Brak, compared to the rest of the district. Our findings describe the burden of a vaccine-preventable disease and reinforce the need for routine 4CmenB introduction, especially in groups where the disease clusters.

BackgroundSalmonella enterica serovar Infantis (S. Infantis) is one of the ubiquitous serovars of the bacterial pathogen S. enterica and recently has been emerging in many countries worldwide. Nonetheless, not much is known about its epidemiology, host adaptation, and virulence.MethodsEpidemiological and molecular approaches were used together with tissue-culture and mouse models to conduct phenotypic comparison with the model S. enterica serovar Typhimurium.ResultsWe show that S. Infantis is more frequently associated with infections in infants ConclusionsOur results demonstrate previously unknown differences in the epidemiology, virulence pathway expression, and pathogenicity between two highly abundant Salmonella serovars and suggest that native variation in the expression of the SPI-1 regulon is likely to contribute to epidemiological and virulence variation between genetically similar nontyphoidal Salmonella serovars.

Pediatric community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are emerging worldwide. High CA-MRSA carriage rates were previously described in healthy Bedouin children. We assessed demographic, clinical and molecular characteristics of pediatric MRSA infections in southern Israel.The Soroka University Medical Center laboratory serves the entire population of southern Israel, divided into 2 ethnic groups, Bedouins and Jews. All in-hospital MRSA clinical isolates from children 0 to 18 years old obtained in 2016 were included. Health care-associated and community-associated infections were defined according to the Centers for Disease Control and Prevention case definition. All isolates were evaluated for staphylococcal cassette chromosome, Panton-Valentine leukocidin, S. aureus protein A type, pulsed field gel electrophoresis and antimicrobial susceptibility testing.Overall, 95 MRSA isolates (18% of all S. aureus), with 25 different MRSA strains, were identified. Twenty-eight isolates (29.5% of MRSA) belonged to the pediatric clone, rarely observed in Israel, staphylococcal cassette chromosome IV, Panton-Valentine leukocidin positive, S. aureus protein A type 002. All isolates demonstrated identical pulsed-field-gel-electrophoresis fingerprints. Eighty-two percent of infections caused by this clone were community-acquired, mainly observed in young Bedouin children, causing skin and soft-tissue infections. The new clone infection characteristics were similar to those of other CA-MRSA. All isolates of the pediatric clone were susceptible to trimethoprim/sulfamethoxazole, ciprofloxacin, gentamicin, tetracycline, rifampicin and vancomycin; 17.8% were nonsusceptible to erythromycin and clindamycin.The pediatric CA-MRSA clone, previously described only in sporadic cases in Israel, is emerging among healthy, young Bedouin children, typically causing skin and soft-tissue infections. Isolates are susceptible to a variety of non-beta-lactam antibiotics.

Rapid developments in the field of whole genome sequencing (WGS) make in silico antimicrobial resistance (AMR) a target within reach. Campylobacter jejuni is a leading cause of foodborne infections in Israel with increasing rates of resistance. We applied WGS analysis to study the prevalence and genetic basis of AMR in 263 C. jejuni human and veterinary representative isolates retrieved from a national collection during 2003–2012. We evaluated the prediction of phenotypic AMR from genomic data. Genomes were screened by the NCBI AMRFinderPlus and the BioNumerics tools for acquired AMR genes and point mutations. The results were compared to phenotypic resistance determined by broth microdilution. The most prevalent resistant determinants were the multi-drug efflux transporter gene cmeABC (100%), the tetracycline resistance tet(O) gene (82.1%), the quinolone resistance gyrA T861 point mutation (75.7%), and the aadE streptomycin resistance gene. A variety of 12 known β lactam resistance genes (blaOXA variants) were detected in 241 (92%) isolates, the most prevalent being blaOXA−193, blaOXA−461, and blaOXA−580 (56, 16, and 7%, respectively). Other aminoglycoside resistance genes and the macrolide resistance point mutation were rare (

Background Campylobacter spp. are the leading cause of foodborne infection worldwide, with a seasonal disease peak that might be affected by temperature increase. We studied the relationship between ambient temperature and weekly notified Campylobacter spp.infections. Methods Data on 29,762 laboratory-confirmed cases of Campylobacter infection for the period, January, 1999 to December, 2010 were retrieved from the Ministry of Health registry. To estimate the association between the number of weekly cases of Campylobacter infection and the national average temperature at lags 0–3 weeks, firstly, we used GAM models, and secondly two-segment piecewise linear Poisson regressions. The effect of temperature was adjusted for seasonality, long-term trends and holidays. Results We found a J-shaped relationship between ambient temperature and notified Campylobacter spp. cases. For C. jejuni in all ages, the curve below the threshold was constant and the percent increase in cases for 1 °C above a threshold of 27 °C was 15.4% (95%CI: 6.7–24.1%). For ages 3–10 yr and > =26 yr the curve was constant below the threshold and positive above it; the percent increase in cases for 1 °C was 17.7%(95%CI: 6.0–29.4%) and 23.7%(95%CI: 11.6–35.8%), respectively. For ages 0–2 yr the curve was linear with no threshold and the percent increase for 1 °C was 5.1%(95%CI: 2.1–8.1%). For ages 11–25 yr the curve was always constant. Results for C. coli were similar. Conclusion Our findings indicate that higher temperatures throughout the year affect Campylobacter spp. morbidity, especially in younger children. This should be taken into consideration in public education and health system preparedness for temperature increases as a result of climate change.

Whole-genome sequencing unveiled host and environment-related insights to Shigella sonnei transmission within cyclic epidemics during 2000-2012 in Israel. The Israeli reservoir contains isolates belonging to S. sonnei lineage III but of different origin, shows loss of tetracycline resistance genes, and little genetic variation within the O antigen: highly relevant for Shigella vaccine development.

Israel implemented use of 7- and 13-valent pneumococcal vaccine in 2009 and 2010, respectively. We describe results of prospective, population-based, nationwide active surveillance of Streptococcus pneumoniae serotype 12F (Sp12F) invasive pneumococcal disease (IPD) dynamics in the 7 years after vaccine introduction. Of 4,573 IPD episodes during July 2009–June 2016, a total of 434 (9.5%) were caused by Sp12F. Sp12F IPD rates (cases/100,000 population) increased in children 3.9 since 2011–2012, followed by an increase in all ages. During 2011–2016, Sp12F was the most prevalent IPD serotype. Sp12F isolates were mostly penicillin nonsusceptible (MIC >0.06 µg/mL; MIC50 = 0.12) and predominantly of sequence type 3774), a clone exclusively found in Israel (constituting ≈90% of isolates in 2000–2009). The sharp increase, long duration, and predominance of Sp12F IPD after vaccine implementation reflect a single clone expansion and may represent more than a transient outbreak.

Non-typhoidal Salmonella enterica (NTS) are diverse and important bacterial pathogens consisting of more than 2600 different serovars, with varying host-specificity. Here, we characterized the poultry-associated serovars in Israel, analysed their resistome and illuminated the molecular mechanisms underlying common multidrug resistance (MDR) patterns. We show that at least four serovars including Infantis, Muenchen, Newport and Virchow present a strong epidemiological association between their temporal trends in poultry and humans. Worrisomely, 60% from all of the poultry isolates tested (n = 188) were multidrug resistant, mediated by chromosomal SNPs and different mobile genetics elements. A novel streptomycin-azithromycin resistance island and previously uncharacterized versions of the mobilized Salmonella genomic island 1 (SGI1) were identified and characterized in S. Blockley and S. Kentucky isolates respectively. Moreover, we demonstrate that the acquisition of SGI1 does not impose fitness cost during growth under nutrient-limited conditions or in the context of Salmonella infection in the mouse model. Overall, our data emphasize the role of the poultry production as a pool of specific epidemic MDR strains and autonomous genetic elements, which confer resistance to heavy metals and medically relevant antibiotics. These are likely to disseminate to humans via the food chain and fuel the increasing global antibiotic resistance crisis.

Background Invasive group A streptococcal (iGAS) infection in the peripartum setting is a rare but devastating disease occasionally occurring as a health care–associated infection (HAI). Current guidelines suggest enhanced surveillance and streptococcal isolate storage after a single case of iGAS, as well as a full epidemiological investigation that includes screening health care workers (HCWs) from several sites after 2 cases. Current guidelines do not recommend routine screening of household members of a patient with iGAS. Methods We conducted studies of 3 patients with iGAS puerperal sepsis and related epidemiologic and molecular investigations. Results Identical GAS emm gene types were found in pharyngeal cultures of 3 asymptomatic spouses of patients with iGAS puerperal sepsis. HCWs screened negative for GAS, and emm typing indicated that other iGAS cases from this hospital were sporadic and not related to the puerperal cases. Conclusions The concurrent presence of the same emm type in a household member practically excludes the option of an inadvertent HAI or facility outbreak. Hence, we suggest that screening close family members for asymptomatic GAS carriage should be performed early as a part of infection prevention measures, as doing so would have significant utility in saving time and resources related to a full epidemiological inquiry.

Beta-hemolytic group G streptococci (GGS) are increasingly recognized as a source of substantial morbidity, causing mild to severe sporadic infections as well as outbreaks. The purpose of this study was to determine the genetic diversity and antibiotic resistance of GGS in Israel in order to aid in prevention and control. A total of 325 GGS isolates were collected in Israel between 2007 and 2011 from three determined settings: (1) carriage (n = 60), an observational longitudinal carriage study in the IF, (2) non-invasive (n = 166), clinical sporadic and epidemic non-invasive cases in the IDF, and (3) invasive (n = 99) cases of bacteremia collected during this period in Israel from a similar age group, at the national Streptococcal Reference Center. All isolates were characterized genetically and by their antibiotic-resistance profile. emm typing revealed 35 distinct types and subtypes among 228 S. dysgalactiae subsp. equisimilis (SDSE) isolates, with high genetic diversity. An additional 97 GGS were identified as Streptococcus anginosus (SAG). The proportion of SDSE was higher in the invasive (100 %) and non-invasive (63.8 %) isolates compared to the carriage ones (38.3 %). Clindamycin, erythromycin, azithromycin and tetracycline resistance was detected in 6.6 %, 8.6 %, 9.7 % and 37.6 % of isolates, respectively. Overall, the most resistant isolates were in the invasive group and the fewest were in the SAG group. Considerable genetic diversity and common antibiotic resistance were revealed among GGS strains which differed according to the epidemiologic settings. Further clinical, epidemiological and basic research of GGS as a pathogen is warranted.

Background Although chronic infections by typhoidal Salmonella are well-known, prolonged human infections by nontyphoidal Salmonella (NTS) are poorly characterized. Methods We retrospectively analyzed 48 345 culture-confirmed NTS infections that occurred in Israel 1995-2012. A case-control study was performed to identify risk factors associated with persistent infections. Whole-genome-sequencing, pulsed-field gel electrophoresis (PFGE), and a mouse infection model were used to study genetic and phenotypic differences between same-patient persistent, recurring isolates. Results In total, 1047 cases of persistent NTS infections, comprising 2.2% of all reported cases of salmonellosis, were identified. The persistence periods ranged between 30 days to 8.3 years. The majority (93%) of the persistently infected patients were immunocompetent, and 65% were symptomatic with relapsing diarrhea, indicating a distinct clinical manifestation from the asymptomatic carriage of typhoidal Salmonella. Four NTS serovars (Mbandaka, Bredeney, Infantis and Virchow) were found to be significantly more frequently associated with persistence than others. Comparative genomics between early and later isolates obtained from the same patients confirmed clonal infection and showed 0 to 10 SNPs between persistent isolates. A different composition of mobile genetic elements (plasmids and phages) or amino acid substitutions in global regulators was identified in multiple cases. These changes resulted in differences in phenotype and virulence between early and later same-patient isolates. Conclusions These results illuminate the overlooked clinical manifestation of persistent salmonellosis that can serve as a human reservoir for NTS infections. Additionally, we demonstrate mechanisms of in-host microevolution and exhibit their potential to shape Salmonella pathogenicity, antimicrobial resistance and host-pathogen interactions.

Background and aims: Neisseria meningitidis (N. meningitidis) is a Gram-negative bacterium that can cause life-threatening invasive infections referred to as invasive meningococcal disease (IMD). In the last decade the incidence of IMD in Israel is about 1/100,000 population annually. We aimed to describe the epidemiology of IMD in Israel combining epidemiological data and characterization of N. meningitidis isolates. Methods: Invasive infection caused by N. meningitidis is a notifiable disease in Israel. Data were collected by epidemiological investigations and control measures were employed. Laboratory work-up included serogrouping, N. meningitides molecular characterization and whole-genome sequencing. Results: During 1998–2017, 1349 cases of IMD were notified in Israel (mean annual incidence rate 0.94/100,000). The peak incidence rates were observed in infants under 1 year of age (10.9/100,000). Case fatality rate was 9.7%. The majority of the N. meningitidis isolates were of serogroup B (67.9%). During 2007–2017, three clonal complexes (CC) 32, 41/44 and 23 (hyper-invasive clonal complexes) were the leading CC (61%). CC32 was the leading CC causing meningococcemia and mortality. In 2017, 35 isolates were tested for 4CMenB antigens variants; of the serogroup B isolates tested 46.7% showed a match to one or more antigens (fHbp or PorA:VR1), most were ST32 (CC32). Conclusions: Preliminary analysis based on limited number of samples suggests that the 4CMenB coverage would be about half the strains; further research is necessary. Integration of clinical, epidemiological and laboratory data is essential to support decision-making on the introduction of the novel MENB vaccines in Israel.

Objectives: Campylobacter jejuni is responsible for 80% of Campylobacter infections in Israel, a country with a high incidence reaching 91/100,000 population. We studied the phylogeny, diversity and prevalence of virulence factors using whole genome sequencing (WGS) of a national sample of C. jejuni clinical, food, and animal isolates collected over a 10-year period (2003–2012). Methods: C. jejuni isolates (n = 263) were subject to WGS using Illumina sequencing (PE 250bpx2). Raw reads and de novo assemblies were analyzed with the BioNumerics whole genome MLST (wgMLST) pipeline. Reads were screened for 71 virulence genes by the SRST2 script. Allelic profiles were analyzed to create minimum spanning trees and allelic core distances were investigated to determine a reliable cutoff for strain determination. Results: wgMLST analysis of 263 C. jejuni isolates indicated significant diversity among the prevalent clonal complexes (CCs) with CC-21 and CC-353 being the most diverse, and CC-574 the most clonal. Within CC-21, sequence type (ST)-1359 created a separate clade. Human, poultry and bovine isolates clustered together across the different STs. Forty four percent of studied isolates were assigned to 29 genetic clusters. Temporal and geographical relatedness were found among the minority of clusters, while most phylogenetically associated cases appeared diffuse and unassociated epidemiologically. The majority of virulence factors were highly prevalent across the dataset and not associated with genotype, source of isolation or invasiveness. Conversely, all 13 genes associated with type VI secretion system (T6SS) were lineage-related and identified in only 18% of the isolates. T6SS was detected in 95.2% of ST-1359, a common type in Israel. Conclusions: wgMLST supported the assessment that poultry and cattle are likely food sources of infection in Israel. Substantial genetic clustering among C. jejuni isolates suggested multiple point source and diffuse outbreaks that were previously unreported in Israel. The high prevalence of T6SS among ST-1359 isolates is unique to Israel, and requires further investigation. This study exemplifies the importance of studying foodborne pathogens using advanced genomic approaches across the entire spectrum of One Health.

This study analyses the epidemiologic, clinical and molecular findings of all culture-confirmed cases of listeriosis notified from 2010 to 2015 in the Tel Aviv District, which is known to have high rates of listeriosis. All clinical isolates of Listeria monocytogenes were subtyped using two-enzyme pulsed-field gel electrophoresis. During the studied period, 102 cases of listeriosis were notified, including 23 pregnancy-associated cases (23%). Among 79 non-pregnancy-associated cases, 18 had neuro-invasive disease (21%). There were 26 deaths associated with the disease. Using molecular identification, we found a number of clusters of identical bacterial clones, which pointed to possible sources of infection. The high rates of morbidity and mortality resulting from listeriosis, as well as the diverse ways of infection demonstrated in this study, accentuate the need to boost public health actions, in order to raise awareness and better control high-risk contamination routes.

Salmonella enterica is the leading etiologic agent of bacterial food-borne outbreaks worldwide. This ubiquitous species contains more than 2,600 serovars that may differ in their host specificity, clinical manifestations, and epidemiology. To characterize salmonellosis epidemiology in Israel and to study the association of nontyphoidal Salmonella (NTS) serovars with invasive infections, 48,345 Salmonella cases reported and serotyped at the National Salmonella Reference Center between 1995 and 2012 were analyzed. A quasi-Poisson regression was used to identify irregular clusters of illness, and pulsed-field gel electrophoresis in conjunction with whole-genome sequencing was applied to molecularly characterize strains of interest. Three hundred twenty-nine human salmonellosis clusters were identified, representing an annual average of 23 (95% confidence interval [CI], 20 to 26) potential outbreaks. We show that the previously unsequenced S. enterica serovar 9,12:l,v:− belongs to the B clade of Salmonella enterica subspecies enterica , and we show its frequent association with extraintestinal infections, compared to other NTS serovars. Furthermore, we identified the dissemination of two prevalent Salmonella enterica serovar Typhimurium DT104 clones in Israel, which are genetically distinct from other global DT104 isolates. Accumulatively, these findings indicate a severe underreporting of Salmonella outbreaks in Israel and provide insights into the epidemiology and genomics of prevalent serovars, responsible for recurring illness.

Shigella species remains a major diarrhoeagenic agent, affecting mostly children, with global high incidence and high mortality rate specially in developing areas. Although azithromycin is recommended for treatment of shigellosis, there are currently no CLSI susceptibility breakpoints, accordingly no routine antimicrobial susceptibility test is performed in the clinical laboratory. The purpose of this study was to estimate the prevalence, resistance profile and molecular epidemiology of azithromycin non-susceptible Shigella strains in Israel during a three year period. Shigella isolates (n = 1,170) referred to the National Reference Center during 2014-2016, were included in this study. Serotyping was performed by slide agglutination. Resistance genes, mph(A) and erm(B), were identified by PCR and the phenotype profile was determined by broth microdilution (BMD). Genetic relatedness was assessed by wgMLST. Decreased susceptibility to azithromycin (DSA) phenotype and genotype were detected in various Shigella species and serotypes related to diverse genetic backgrounds and antimicrobial profiles: 6% (26/423) of Shigella flexneri and 2% (16/747) of Shigella sonnei displayed DSA (MIC16 mg/L). Correlation of this phenotype with the presence of mph(A) and erm(B) genes was confirmed. All DSA-strains displayed resistance to ≥3 different antimicrobial classes. Among DSA-strains, 14% were resistant to quinolones and 5% displayed resistance to ceftriaxone. Most of these strains (32/42) were isolated from children in the southern and central regions of Israel. Clonality and significant relatedness was confirmed by PFGE and wgMLST. The presence of macrolide resistance genes among the different species and lineages reflects the transmissible nature of these genes. The emergence of DSA-Shigella reinforces the necessity to establish clinical breakpoints that would warrant routine testing, reporting and surveillance for this drug of choice.

During 1999–2010, the annual incidence of Campylobacter spp. infection in Israel increased from 31.04 to 90.99 cases/100,000 population, a yearly increase of 10.24%. Children 26-fold higher than for the 30–

Shigellosis trends in these communities provide insight into global movement of drug-resistant Enterobacteriaceae., Shigellae are sensitive indicator species for studying trends in the international transmission of antimicrobial-resistant Enterobacteriaceae. Orthodox Jewish communities (OJCs) are a known risk group for shigellosis; Shigella sonnei is cyclically epidemic in OJCs in Israel, and sporadic outbreaks occur in OJCs elsewhere. We generated whole-genome sequences for 437 isolates of S. sonnei from OJCs and non-OJCs collected over 22 years in Europe (the United Kingdom, France, and Belgium), the United States, Canada, and Israel and analyzed these within a known global genomic context. Through phylogenetic and genomic analysis, we showed that strains from outbreaks in OJCs outside of Israel are distinct from strains in the general population and relate to a single multidrug-resistant sublineage of S. sonnei that prevails in Israel. Further Bayesian phylogenetic analysis showed that this strain emerged approximately 30 years ago, demonstrating the speed at which antimicrobial drug–resistant pathogens can spread widely through geographically dispersed, but internationally connected, communities.

Summary Objectives To enhance timely surveillance of bacterial enteric pathogens, space-time cluster analysis was introduced in Israel in May 2013. Methods Stool isolation data of Salmonella , Shigella , and Campylobacter from patients of a large Health Maintenance Organization were analyzed weekly by ArcGIS and SaTScan, and cluster results were sent promptly to local departments of health (LDOHs). Results During eighteen months, we identified 52 Shigella sonnei clusters, two Salmonella clusters, and no Campylobacter clusters. S. sonnei clusters lasted from one to 33 days and included three to 30 individuals. Thirty-one (60%) of the S. sonnei clusters were known to LDOHs prior to cluster analysis. Clusters not previously known by the LDOHs prompted epidemiologic investigations. In 31 of the 37 (84%) confirmed clusters, educational institutes (nursery schools, kindergartens, and a primary school) were involved. Conclusions Cluster analysis demonstrated capability to complement enteric disease surveillance. Scaling up the system can further enhance timely detection and control of outbreaks.

Background Legionnaires’ disease (LD) is associated with high mortality rates and poses a diagnostic and therapeutic challenge. Use of the rapid urinary antigen test (UAT) has been linked to improved outcome. We examined the association between the method of diagnosis (UAT or culture) and various clinical and microbiological characteristics and outcome of LD. Methods Consecutive patients with pneumonia and confirmation of Legionella infection by a positive UAT and/or a positive culture admitted between the years 2006–2012 to a university hospital were retrospectively studied. Isolated L. pneumophila strains were subject to serogrouping, immunological subtyping and sequence-based typing. Variables associated with 30-day all-cause mortality were analyzed using logistic regression as well as cox regression. Results Seventy-two patients were eligible for mortality analyses (LD study group), of whom 15.5 % have died. Diagnosis based on positive L. pneumophila UAT as compared to positive culture (OR = 0.18, 95 % CI 0.03–0.98, p = 0.05) and administration of appropriate antibiotic therapy within 2 hospitalization days as compared to delayed therapy (OR = 0.16, 95 % CI 0.03–0.90, p = 0.04) were independently associated with reduced mortality. When controlling for intensive care unit (ICU) admissions, the method of diagnosis became non-significant. Survival analyses showed a significantly increased death risk for patients admitted to ICU compared to others (HR 12.90, 95 % CI 2.78–59.86, p = 0.001) and reduced risk for patients receiving appropriate antibiotic therapy within the first two admissions days compared to delayed therapy (HR 0.13, 95 % CI 0.04–0.05, p = 0.001). Legionella cultures were positive in 35 patients (including 29 patients from the LD study group), of whom 65.7 % were intubated and 37.1 % have died. Sequence type (ST) ST1 accounted for 50.0 % of the typed cases and ST1, OLDA/Oxford was the leading phenon (53.8 %). Mortality rate among patients in the LD study group infected with ST1 was 18.2 % compared to 42.9 % for non-ST1 genotypes (OR = 0.30, 95 % CI 0.05-1.91, p = 0.23). Conclusions The study confirms the importance of early administration of appropriate antibiotic therapy and at the same time highlights the complex associations of different diagnostic approaches with LD outcome. Infection with ST1 was not associated with increased mortality. Genotype effects on outcome mandate examination in larger cohorts.

Received 9 March 2011; Final revision 31 January 2012; Accepted 31 January 2012;first published online 24 February 2012SUMMARYSerological surveys for diphtheria were conducted in six European countries including CzechRepublic, Hungary, Ireland, Latvia, Luxembourg, Slovakia and one country outside Europe,Israel. For each country, a nationally representative population sample was collected across theentire age range and was tested for antibodies to diphtheria toxin. Although each nationallaboratory used its preferred assay, the results were all standardized to those of the in vitroneutralization test and expressed in international units (IU) which allowed comparative analysesto be performed. The results showed that increasing age is related to a gradual increase inseronegative subjects (

To determine whether rapid emergence of Salmonella enterica serovar Infantis in Israel resulted from an increase in different biotypes or spread of 1 clone, we characterized 87 serovar Infantis isolates on the genotypic and phenotypic levels. The emerging strain comprised 1 genetic clone with a distinct pulsed-field gel electrophoresis profile and a common antimicrobial drug resistance pattern.

Vibrio vulnificus is a highly invasive human pathogen and presents a food safety issue worldwide. Human infections caused by V. vulnificus are primarily caused by contaminated seafood consumption or contaminated skin wounds, which can lead to septicemia, wound infections, and high hospitalization and fatality rates (1,2). V. vulnificus strains are biochemically divided into 3 biotypes (BTs). BT3, found in Israel, is associated with infections caused by contaminated fish (3). Until now, only 3 BT3 isolates had been isolated from the environment in direct contrast with their large clinical numbers (3,4). BT3 is a clonal group, which various molecular methods have failed to differentiate among its strains, (4,5) with the exceptions of rep-PCR (6), simple-sequence repeats (SSR) (7), and recently pulsed-field gel electrophoresis (PFGE) (8). SSR analysis of V. vulnificus was highly discriminative among BT3 strains (7). These SSR markers have been used for typing and for epidemiologic studies in many bacterial species (9,10). We present results from a 3-year monitoring program of clinical and environmental V. vulnificus using SSR as an epidemiologic genotyping tool.

SUMMARYStreptococcus pyogenesgroup A (GAS) is a primary human pathogen. We performed geneticemmsequence and serological T-antigen typing of 819 mostly invasive GAS isolates recovered in Israel during 1996–2005. Of the 72emmtypes found, the six most prevalent types (1, 81, 89, 14, 28, 5) comprised 30·2% of all isolates, andemm-type changes were observed over the years. The predicted coverage of the 26-valentS. pyogenesvaccine formulated for usage in the USA was predicted to be only ~60%. On the basis of differentemm–T antigen type associations, some Israeli strains are probably different clonal types than those found in USA. About 2% of GAS hademmtypes that were originally associated withS. dysgalactiaesubsp.equisimilis emmgenes. Therefore, routineemmtyping allows meaningful GAS strain surveillance, and provides data relevant to better vaccine coverage.

Salmonella Senftenberg is uncommon in the United Kingdom. In January-June 2007, the Health Protection Agency reported on 55 primary human cases of Salmonella Senftenberg in England and Wales. In May 2007, fresh basil sold in the United Kingdom was found to be contaminated with Salmonella Senftenberg. We launched an investigation to elucidate the cause of this outbreak. Isolates were examined using plasmid profiling and pulsed-field gel electrophoresis, and the outbreak strain (SSFTXB.0014) was identified. We enquired via Enter-net whether other countries had isolated the outbreak strain, analyzed samples of fresh herbs from U.K. retailers, and interviewed patients on food history. Thirty-two patient-cases were referred to this outbreak in England and Wales. Onsets of illness occurred between 5 March and 6 June 2007. Fifty-six percent of patient-cases were females and 90% adults (>20 years old); three were admitted to hospital as a result of Salmonella infection. Scotland, Denmark, the Netherlands, and the United States reported on 19 cases of Salmonella Senftenberg infection presenting with the outbreak strain since January 2007. Eight samples of prepacked fresh basil imported from Israel tested positive with the same strain. A minority of patients could recall the consumption of basil before illness, and some reported consumption of products where basil was a likely ingredient. Environmental investigations in Israel did not identify the contamination source. Microbiological evidence suggested an association between contamination of fresh basil and the cases of Salmonella Senftenberg infection, leading to withdrawal of basil from all potentially affected batches from the U.K. market.

Vibrio cholerae is the etiological agent of cholera. Its natural reservoir is the aquatic environment. To date, practical typing of V. cholerae is mainly serological and requires about 200 antisera. Simple sequence repeats (SSR), also termed VNTR (for variable number of tandem repeats), provide a source of high genomic polymorphism used in bacterial typing. Here we describe an SSR-based typing method that combines the variation in highly mutable SSR loci, with that of shorter, relatively more stable mononucleotide repeat (MNR) loci, for accurate and rapid typing of V. cholerae . In silico screening of the V. cholerae genome revealed thousands of perfect SSR tracts with an average frequency of one SSR every 152 bp. A panel of 32 V. cholerae strains, representing both clinical and environmental isolates, was tested for polymorphism in SSR loci. Two strategies were applied to identify SSR variation: polymorphism of SSR tracts longer than 12 bp (L-SSR) assessed by capillary fragment-size analysis and MNR polymorphism assessed by sequencing. The nine L-SSR loci tested were all polymorphic, displaying 2 to 13 alleles per locus. Sequence analysis of eight MNR-containing loci (MNR-multilocus sequence typing [MLST]) provided information on both variations in the MNR tract itself, and single nucleotide polymorphism (SNP) in their flanking sequences. Phylogenetic analysis of the combined SSR data showed a clear discrimination between the clinical strains belonging to O1 and O139 serogroups, and the environmental isolates. Furthermore, discrimination between 27 strains of the 32 strains was achieved. SSR-based typing methods combining L-SSR and MNR-MLST were found to be efficient for V. cholerae typing.

Routine susceptibility testing of 5,616 Shigella isolates at the National Shigella Reference Centre in Israel over a 5-year period (2000-2004) revealed resistance to ceftriaxone in one strain of Shigella boydii 2 and in two strains each of Shigella flexneri 2a, S. flexneri 6, and Shigella sonnei. All seven isolates were confirmed as producers of extended-spectrum beta-lactamase (ESBL) by the combination disk method, the Vitek 1 system, and a modification of the double-disk synergy test, which is based on the inhibitory properties of clavulanic acid, tazobactam, and sulbactam. Tazobactam had the strongest effect in all seven strains. Molecular characterization of the ESBLs identified CTX-M-type enzymes, consisting of the CTX-M-9 group (n = 3), CTX-M-3 (n = 2), CTX-M-39 (n = 1), and CTX-M-2 group (n = 1). Three of the strains also carried bla-(OXA) genes and a bla-(TEM) gene. Although the prevalence of ESBLs in this study was low, further research is needed on the spread and transfer of resistance genes, both in hospitals and in the community.

SUMMARYThe incidence of invasive infections due toNeisseria meningitidisin Israel is about 1/100 000 population annually. Three cases of meningococcal meningitis were reported in employees at a single plant; the first case appeared in March 2013 and the second and third cases appeared in December, almost 9 months later.N. meningitidisserogroup B was isolated from cerebrospinal fluid samples. Multilocus sequence typing assigned the three meningococcal isolates to ST10418, a new sequence type and a member of the ST32 clonal complex. The clonality was confirmed by performance of pulsed-field gel electrophoresis. Post-exposure antibiotic prophylaxis was administered to close contacts of the first case. Upon the diagnosis of the additional two cases, post-exposure prophylaxis was administered to all the plant employees. This report demonstrates the importance of combining public health measures and advanced laboratory studies to confirm clonality and to prevent further disease spread in a closed setting.

This study outlines the unique epidemiology of Salmonella enterica serotype Virchow in Israel. Between 1997 and 2002, the overall incidence of non-typhoid Salmonella enterica (NTS) decreased from 69.3 to 53.3 infections/100 000 population, but the incidence of S. Virchow increased (from 7.2 to 9.1 infections / 100 000). Since 2000, S. Virchow has become the second-ranking NTS isolate, accounting for 17% and 27% of all stool and blood NTS isolates, respectively. Infants aged < 1 year had the highest incidence of isolation from stools (92.8/100 000). The incidence of isolation from blood was highest for infants aged

During a period of four years, multidrug-resistant Escherichia coli of particular serotypes have been isolated from 255 elderly (65 years) patients from four hospitals in central Israel. 83% of the isolates belonged to one of four predominant serotypes (O153:H31, O101:H-, O2:H42, and O102:H6). All isolates were producers of extended spectrum beta-lactamases and resistant to ciprofloxacin. To our knowledge, the involved serotypes have hitherto not been reported as etiological agents of extraintestinal human infections (MEDLINE). Pulsed-field gel electrophoresis of isolates from one of the most frequent serotypes indicated a clonal relationship between them. Further investigation of these strains and analysis of their virulence factors may help to confine their spread.

Recurrent group G Steptococcus bacteremia, associated with lymphatic disorders and possibly emm stG840.0, is described., Group G Streptococcus (GGS) can cause severe infections, including bacteremia. These organisms often express a surface protein homologous to the Streptococcus pyogenes M protein. We retrospectively studied the characteristics of patients from the Hadassah Medical Center with GGS bacteremia from 1989 to 2000. Ninety-four cases of GGS bacteremia were identified in 84 patients. The median age was 62 years, 54% were males, and 92% had underlying diseases (35% had a malignancy, and 35% had diabetes mellitus). The most frequent source for bacteremia was cellulitis (61%). emm typing of 56 available isolates disclosed 13 different types, including 2 novel types. Six patients had recurrent bacteremia with two to four bacteremic episodes, five had chronic lymphatic disorders, and two had emm type stG840.0 in every episode. Recurrent bacteremia has not been described for invasive group A Streptococcus. We describe an entity of recurrent GGS bacteremia, which is associated with lymphatic disorders and possibly with emm stG840.0.

Background Listeria monocytogenes is a foodborne pathogen that causes life-threatening infections in elderly, immunocompromised, and pregnant women. In pregnancy it may cause fetal loss or a preterm delivery, and the neonate is prone to neonatal sepsis and death. Methods We created a cohort of all L. monocytogenes cases during 10 years (1998-2007) in Israel, by a comprehensive review of cases in hospitals throughout the country and cases reported to the Ministry of Health. Results One hundred sixty-six pregnancy-related listeriosis cases were identified, resulting in a yearly incidence of 5-25 cases per 100 000 births. Presentation associated with fetal demise was more common in the second trimester (55.3%), and preterm labor (52.3%) and abnormal fetal heart rate monitoring (22.2%) were more common in the third trimester (P = .001). Fetal viability was low in the second trimester (29.2%) and much higher (95.3%) in the third trimester. Each additional week of pregnancy increased the survival chance by 33% (odds ratio, 1.331 [95% confidence interval, 1.189-1.489]). A single case of maternal mortality was identified. Listeria monocytogenes serotype 4b was more common in pregnancy-related than in non-pregnancy-related cases (79.5% vs 61.3%, P = .011). Pulsed-field gel electrophoresis analysis suggested that 1 pulsotype is responsible for 35.7% of the pregnancy cases between 2001 and 2007. This clone is closely related to the Italian gastroenteritis-associated HPB2262 and the invasive US Scott A L. monocytogenes strains. Conclusions Our survey emphasizes the high rate of pregnancy-related listeriosis in Israel and shows that specific clones might account for this.

National surveillance of Legionnaires‘ disease (LD) is important to inform control measures and facilitate international networking for timely reporting. This study is the first to describe the molecular epidemiology of LD in Israel. Case notifications for 2006–2011, collated through mandatory reporting, were identified and demographic, clinical and laboratory data were extracted. Unrelated clinical and environmental Legionella pneumophila strains were characterized using standard procedures, Dresden panel of monoclonal antibodies and the ESCMID Study Group for Legionella Infections (ESGLI) Sequence-Based Typing scheme. In all, 294 cases were reported (crude incidence 0.67 cases/100 000; age-standardized incidence 1/100 000). LD epidemiological trends and features largely resembled those of the EU, except for a larger proportion of nosocomial cases. Of 28 clinical and 23 environmental strains analysed, 71.4% and 21.7% were serogroup (sg) 1 and the most common immunological subgroup was OLDA/Oxford (64%). Of the clinical strains, OLDA/Oxford, ST1 was the most common (43%) followed by Allentown/France, ST40 (14%). The unusual sg 3 ST338 was found in 17.4% of environmental strains. Novel STs were detected amongst 23.5% of strains. These findings warrant further molecular investigation. Molecular epidemiology data generated from neighbouring countries newly adopting the ESGLI typing scheme for L. pneumophila contribute to understanding of regional strain diversity.

The incidence of Campylobacter infection in Israel, particularly among children2 years of age, has risen over the last decade and became one of the highest among industrialized countries. This study explored the molecular epidemiology of Campylobacter jejuni in Israel over a decade (2003-2012) using multilocus sequence typing (MLST) combined with demographic metadata. Representative clinical isolates (438) from a large national repository together with selected veterinary isolates (74) were subject to MLST. The distribution of age groups, ethnicity and clinical source across various genotypes was evaluated using Poisson modelling. The 512 studied isolates were assigned 126 distinct sequence types (STs) (18.8% novel STs) grouped into 21 clonal complexes (CCs). Most human, poultry and bovine STs clustered together in the leading CCs. Three dominant STs (ST21, ST6608, ST4766) were detected only since 2006. Patients infected with the leading CCs were similarly distributed along densely populated areas. The frequency of blood isolates was higher in patients infected with CC353 (relative rate (RR)=2.0, 95% CI 1.03-3.9, adjusted p value (adj.p) 0.047) and CC42 (RR=4.4, 95% CI 1.7-11.6, adj.p 0.018) and lower with CC257 (RR=0.3, 95% CI 0.1-0.9, adj. p 0.047). The distribution of age groups and ethnicity also varied across the leading CCs. In conclusion, C. jejuni isolates in a national sample appeared highly diverse with a high proportion of new STs. Phylogenic analysis was compatible with poultry and cattle as possible food sources of clinical infection. Demographic characteristics of the infected patients coupled with strain invasiveness across different genotypes revealed a complex epidemiology of C. jejuni transmission in Israel.

Epidemiological data on community acquired methicillin-resistant-Staphylococcus aureus (CA-MRSA) carriage and infection in the Middle-East region is scarce with only few reports in the Israeli and Palestinian populations. As part of a Palestinian-Israeli collaborative research, we have conducted a cross-sectional survey of nasal S. aureus carriage in healthy children and their parents throughout the Gaza strip. Isolates were characterized for antibiotic susceptibility, mec gene presence, PFGE, spa type, SCCmec-type, presence of PVL genes and multi-locus-sequence-type (MLST). S. aureus was carried by 28.4% of the 379 screened children-parents pairs. MRSA was detected in 45% of S. aureus isolates, that is, in 12% of the study population. A single ST22-MRSA-IVa, spa t223, PVL-gene negative strain was detected in 64% of MRSA isolates. This strain is typically susceptible to all non-β-lactam antibiotics tested. The only predictor for MRSA carriage in children was having an MRSA carrier-parent (OR = 25.5, P = 0.0004). Carriage of the Gaza strain was not associated with prior hospitalization. The Gaza strain was closely related genetically to a local MSSA spa t223 strain and less so to EMRSA15, one of the pandemic hospital-acquired-MRSA clones, scarcely reported in the community. The rapid spread in the community may be due to population determinants or due to yet unknown advantageous features of this particular strain.

Enteric fever is an invasive life-threatening systemic disease caused by the Salmonella enterica human-adapted serovars Typhi and Paratyphi. Increasing incidence of infections with Salmonella enterica serovar Paratyphi A and the spreading of its antibiotic-resistant derivates pose a significant health concern in some areas of the world. Herein, we describe a molecular and phenotypic characterization of an S . Paratyphi A strain accounted for a recent paratyphoid outbreak in Nepal that affected at least 37 travelers. Pulsed-field gel electrophoresis analysis of the outbreak isolates revealed one genetic clone (pulsotype), confirming a single infecting source. Genetic profiling of the outbreak strain demonstrated the contribution of specific bacteriophages as a prime source of genetic diversity among clinical isolates of S . Paratyphi A. Phenotypic characterization in comparison with the S . Paratyphi A ATCC 9150 reference sequenced strain showed differences in flagellar morphology and increased abilities of the outbreak strain with respect to its motility, invasion into nonphagocytic cells, intracellular multiplication, survival within macrophages, and higher induction of interleukin-8 (IL-8) secreted by host cells. Collectively, these differences suggest an enhanced virulence potential of this strain and demonstrate an interesting phenotypic variation among S . Paratyphi A isolates. In vivo profiling of 16 inflammatory cytokines in patients infected with the outbreak strain revealed a common profile of a remarkable gamma interferon (IFN-γ) induction together with elevated concentrations of tumor necrosis factor alpha (TNF-α), IL-6, IL-8, IL-10, and IL-15, but not IL-12, which was previously demonstrated as elevated in nontyphoidal Salmonella infections. This apparent profile implies a distinct immune response to paratyphoid infections.

Foodborne Salmonella enterica outbreaks constitute both a threat to public health and an economic burden worldwide.To characterize the pathogen(s) involved and possible source of infection of an outbreak of acute gastroenteritis in a banqueting hall in Jerusalem.We conducted interviews of guests and employees of the banqueting hall, and analyzed food items, samples from work surfaces and stool cultures.Of 770 persons participating in three events on 3 consecutive days at a single banqueting hall, 124 were interviewed and 75 reported symptoms. Salmonella enterica, serovar Enteritidis, phage type C-8, was isolated from 10 stool cultures (eight guests, one symptomatic employee and one asymptomatic employee) and a sample of a mayonnaise-based egg salad. Pulsed-field gel electrophoresis of the isolates revealed an identical pattern in the outbreak isolates, different from SE C-8 controls. A culture-positive asymptomatic employee was linked to all three events. After a closure order, allowing for cleaning of the banqueting hall, revision of food preparation procedures and staff instruction on hygiene, the banqueting hall was reopened with no subsequent outbreaks.It is often difficult to pinpoint the source of infection in S. enterica outbreaks. Using molecular subtyping methods, a link was confirmed between patients, a food handler (presumably a carrier) and a food item--all showing an identical specific Salmonella enterica serovar Enteritidis. Testing asymptomatic as well as symptomatic food handlers in outbreak investigations is imperative. Pre- and post-hiring screening might be considered as preventive measures; hygiene and sanitation education are essential.

Background. Ecthyma is an invasive, ulcerated skin infection. Four ecthyma outbreaks occurred in different infantry units in the Israeli Defense Force from October 2004 through February 2005. Morbidity attack rates in the first 3 outbreaks were 89% (49 of 55 soldiers), 73% (32 of 44), and 82% (37 of 45). In the fourth outbreak, in which early intervention (antimicrobial treatment and improvement of hygiene) was applied, the attack rate was 25% (10 of 40 soldiers). In the first outbreak cluster, 4 soldiers experienced poststreptococcal glomerulonephritis, and 5 cases of systemic sequelae were recorded (1 case of severe septic shock, 3 cases of pneumonia, and 1 case of septic olecranon bursitis). Methods. Streptococcus pyogenes and Staphylococcus aureus were isolated from ecthyma sores, oropharynx, and anterior nares of affected and unaffected soldiers involved in all 4 outbreaks. Results. Although the S. aureus isolates had different genomic profiles, >90% of S. pyogenes isolates were identified as belonging to a single clone, emm type 81, T type 8. Epidemiological investigation revealed that the hygiene levels of the soldiers and their living conditions were probably the most important cause for the difference in attack rates, wound severity, and systemic sequelae found between and within the units. Conclusions. Our study demonstrates the possible ramifications of the combination of a virulent and highly infective S. pyogenes strain and poor living conditions, and it emphasizes the importance of early intervention in such conditions.

The genetically distinct biotype 3 has penetrated Israeli freshwaters and is causing severe illness in persons who handle tilapia or carp., During 1996–1997, a new Vibrio vulnificus biotype 3, which caused severe soft tissue infection after fishbone injury, emerged in Israel. We conducted a follow-up study from 1998 through 2005 to assess changing trends, outcomes, and molecular relatedness of the implicated strains. A total of 132 cases (71% confirmed and 29% suspected) of V. vulnificus biotype 3 infection were found. Most infections (95%) were related to percutaneous fish exposure, mainly tilapia (83%) or common carp (13%). Bacteremia, altered immune status, and history of ischemic heart disease were identified as independent risk factors for death, which reached a prevalence of 7.6%. Pulsed-field gel electrophoresis patterns of strains from 1998 through 2005 and from 1996 through 1997 showed a high degree of homogeneity and were distinct from those of V. vulnificus biotype 1. Infections caused by V. vulnificus biotype 3 continue affect the public’s health in Israel.

SUMMARYNeisseria meningitidisis an important cause of childhood meningitis and septicaemia. Between 1999 and 2005, 133 invasive meningococcal disease (IMD) cases occurred in Jerusalem, 112 (84·2%) of them in children aged 0–14 years. The annual incidence rate in Jerusalem was higher than the national average (2·45±0·6vs. 1·13±0·16/100 000 population,P=0·002). Most of the children (82·1%) were from low socio-economic Arab and Jewish ultra-orthodox communities; mortality was higher among Arab than Jewish children (1·3vs. 0·22/100 000 person-years,P=0·004). A cluster of 10 children with severe meningococcal sepsis (three fatalities) emerged in the winter of 2003–2004. Compared to the other 102 cases in 1999–2005 both meningococcaemia (100%vs. 51%,P=0·003) and mortality (30%vs. 6·9%,P=0·014) rates were higher. Serogroup B comprised 77·6% of the bacterial isolates. Pulsed-field gel electrophoresis showed considerable variability among cluster isolates, but significant resemblance in Arab cases throughout 1999–2005. The increased susceptibility of specific sub-populations to IMD necessitates further evaluation.

Contamination of food with streptococci could present with unusual outbreaks that may be difficult to recognize in the early stages. This is demonstrated in a large food-borne outbreak of streptococcal pharyngitis that occurred in 2003 in a factory in Israel. The outbreak was reported to the public health services on July 2 and an epidemiologic investigation was initiated. Cases and controls were interviewed and throat swabs were taken. An estimated 212 cases occurred within the first 4 days, the peak occurring on the second day. There was a wave of secondary cases during an additional 11 days. The early signs were of a respiratory illness including sore throat, weakness and fever, with high absenteeism rates suggesting a respiratory illness. As part of a case-control study, cases and controls were interviewed and throat swabs taken. Illness was significantly associated with consumption of egg-mayonnaise salad (odds ratio 4.2, 95% confidence interval 1.4-12.6), suggesting an incubation period of 12-96 hours. The initial respiratory signs of food-borne streptococcal pharyngitis outbreaks could delay the identification of the vehicle of transmission. This could be particularly problematic in the event of deliberate contamination.

A seroepidemiological study was performed to evaluate immunity to diphtheria and to determine the correlates of diphtheria toxoid antibody levels among children and adults in Israel. In total, 3185 sera from an age-stratified sample of children and adults, obtained in 2000–2001, were tested for diphtheria toxoid antibodies by an in-house double-antigen ELISA. A level of ≤0.01 IU /mL (no immune protection or seronegativity) was found in 168 (5.3%) of the 3185 subjects, 639 (20.1%) had antibody levels of 0.011–0.099 IU /mL (basic immunity or low seropositivity), and 2378 (74.7%) had antibody levels ≥0.1 IU /mL (full protection or seropositivity). Seronegativity increased significantly in subjects aged >50 years, reaching levels of 9.7%, 12.6% and 18.9% in the groups aged 50–54, 55–59 and >60 years, respectively (p 0.001), with rates of basic immunity following a similar pattern. Subjects born abroad had higher seronegativity rates than those born in Israel (7.7%vs. 4.9%; p 0.019). No difference in diphtheria toxoid antibody levels was found according to other demographical variables, such as gender, Jewish or Arab ethnicity, urban or rural settlements, and the subjects’ place of residence. The level of immunity to diphtheria among children and adults in Israel was satisfactory, with the exception of individuals aged >50 years. The risk of diphtheria outbreaks is low, but sporadic cases may occur among individuals lacking basic immunity against the disease.

Background Bacterial and viral enteric pathogens are the leading cause of diarrhea in infants and children. We aimed to identify and characterize the main human diarrheagenic E. coli (DEC) in stool samples obtained from children less than 5 years of age, hospitalized for acute gastroenteritis in Israel, and to examine the hypothesis that co-infection with DEC and other enteropathogens is associated with the severity of symptoms. Methods Stool specimens obtained from 307 patients were tested by multiplex PCR (mPCR) to identify enteroaggregative E. coli (EAEC), enterohemorrhagic (EHEC), enteropathogenic E. coli (EPEC) and enterotoxigenic E. coli (ETEC). Specimens were also examined for the presence of rotavirus by immunochromatography, and of Shigella, Salmonella and Campylobacter by stool culture; clinical information was also obtained. Results Fifty nine (19%) children tested positive for DEC; EAEC and atypical EPEC were most common, each detected in 27 (46%), followed by ETEC (n = 3; 5%), EHEC and typical EPEC (each in 1 child; 1.5%). Most EAEC isolates were resistant to cephalexin, cefixime, cephalothin and ampicillin, and genotypic characterization of EAEC isolates by O-typing and pulsed-field gel electrophoresis showed possible clonal relatedness among some. The likelihood of having > 10 loose/watery stools on the most severe day of illness was significantly increased among patients with EAEC and rotavirus co-infection compared to children who tested negative for both pathogens: adjusted odds ratio 7.0 (95% CI 1.45-33.71, P = 0.015). Conclusion DEC was common in this pediatric population, in a high-income country, and mixed EAEC and rotavirus infection was characterized by especially severe diarrhea.