Tamar Shohat

Blood invasiveness of Salmonella enterica as a function of age and serotype

We explored the dual influence of the patients age and the infecting serotype on the blood invasiveness patterns of non-Typhi Salmonella enterica (NTS). Blood invasiveness ratio (BIR) was calculated as the ratio between the number of blood and blood + stool isolates. Analysis of 14,951 NTS isolates showed that the BIR increased drastically above the age of 60 years, reaching levels 3.5-7 times higher compared to age group < 2 years. Different patterns of age-related invasiveness were observed for the five most common NTS serotypes (Enteritidis, Typhimurium, Virchow, Hadar, Infantis). Among children < 2 years, the BIR was highest for serotype Virchow and lowest for serotype Hadar, while in persons > or = 60 years it was highest for serotypes Enteritidis and lowest for serotype Infantis. The tendency of NTS serotypes to invade the bloodstream was significantly influenced by the patients age, however the impact of age differed for various NTS serotypes.

Invasive Bacterial Infections in Relation to Influenza Outbreaks, 2006–2010

BACKGROUND We aimed to define the excess morbidity associated with bloodstream infections (BSIs), imposed by pandemic H1N1 influenza during 2009-2010 (pH1N1/2009-2010) and seasonal influenza. METHODS Eight hospitals, accounting for 33% of hospitalizations in Israel, provided data on BSI during 2006-2010. The age-specific incidence of BSI due to Streptococcus pneumoniae, Staphylococcus aureus, and Streptococcus pyogenes was determined. BSI incidence rate ratios (IRRs) during seasonal and pH1N1 influenza seasons were assessed. RESULTS Regular influenza seasons were characterized by increased rates of S. pneumoniae BSI but with no increase in S. aureus and S. pyogenes BSI rates. The pH1N1/2009-2010 influenza outbreak was characterized by (1) higher rates of S. pneumoniae bacteremia among children but not among adults (IRRs for S. pneumoniae BSI among children aged 0-4 years during the summer and winter of 2009-2010 were 14.8 [95% confidence interval {CI}, 5-43.7] and 6.5 [95% CI, 3.6-11.8], compared with 2006-2009 summers and influenza-active winter weeks, respectively [P < .0001]), higher rates of S. aureus BSI in all age groups (IRRs during the summer and winter of 2009-2010 were 1.6 [95% CI, 1.4-1.9] and 1.5 [95% CI, 1.2-1.7], compared with 2006-2009 summers and influenza-active weeks, respectively [P < .0001]), higher rates of S. pyogenes BSI during 2009-2010 influenza season (IRR 2.7 [95% CI, 1.6-4.6] and 3.3 [95% CI, 1.9-5.8] during the summer and winter of 2009-2010, compared with 2006-2009 summers and influenza-active weeks, respectively [P < .0001]). CONCLUSIONS pH1N1 influenza seasons were characterized by marked increases in invasive S. aureus and S. pyogenes infections among children and adults, with the highest increase in S. pneumoniae BSI among children.

Urinary concentrations of polycyclic aromatic hydrocarbons in Israeli adults: Demographic and life-style predictors

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants associated with adverse health outcomes, including cancer, asthma, and reduced fertility. Because data on exposure to these contaminants in Israel and the Middle East are very limited this study was conducted to measure urinary levels of PAHs in the general adult population in Israel and to identify demographic and life-style predictors of exposure. We measured concentrations of five PAH metabolites: 1-hydroxypyrene (1OH_pyrene) and four different hydroxyphenanthrenes (1-hydroxyphenanthrene, 2-hydroxyphenanthrene, 3-hydroxyphenanthrene, 4-hydroxyphenanthrene), as well as cotinine in urine samples collected from 243 Israeli adults from the general population. We interviewed participants using structured questionnaires to collect detailed demographic, smoking and dietary data. For over 99% of the study participants, urinary concentration of at least one of the PAHs was above both the limit of detection (LOD) and the limit of quantification (LOQ). All PAHs were significantly correlated (rho=0.67-0.92). Urinary concentration of hydroxyphenanthrenes, but not 1OH_pyrene, was significantly higher among Arabs and Druze study participants (N=56) compared to Jewish participants (N=183). For 4-hydroxyphenanthrene, concentration in Arabs and Druze was 1.95 (95% CI 1.50-2.52) that of Jews, after controlling for creatinine, age and cotinine levels. Urinary concentrations of all PAHs were significantly higher among current smokers or participants with higher cotinine levels and increased significantly with smoking frequency. While PAHs concentrations were not associated with cotinine concentrations in nonsmokers in the overall study population, PAHs concentration was significantly higher among nonsmoking Jews with cotinine ≥LOQ (1μg/L), which represents exposure to environmental tobacco smoking, compared to nonsmoking Jews with cotinine concentrations <LOQ, with the highest ratio for 1OH_pyrene (Ratio=2.38, 95% CI 1.47-3.85). Among nonsmoking Arabs and Druze, higher hydroxyphenanthrenes concentrations were found for those consuming grilled food once a month or more. For 3-hydroxyphenanthrene, concentration in those consuming grilled food once a month or more was 2.72 (95% CI 1.01-4.98) times that of those consuming grilled food less than once a month or not at all, after controlling for creatinine, age and cotinine levels. In conclusion, we found that the general adult population in Israel is widely exposed to PAHs. Exposure differed by ethnic sub-groups both in magnitude and sources of exposure. The finding of higher exposure among Arabs and Druze highlights disparities in environmental exposures across subpopulations and suggests that further research and preventive measure are warranted to reduce PAHs exposure and associated health outcomes, especially in the Arab population in the Middle East.

Significant cross reactive antibodies to influenza virus in adults and children during a period of marked antigenic drift.

BackgroundLittle is known about the development of cross-reactive antibodies following natural exposure to pathogens. Such knowledge is critical in the development of new universal influenza vaccines.MethodsTo study the possibility of the presence of cross-reactive antibodies to influenza viruses which underwent a major antigenic drift between the years 1999 and 2007 sera from samples of 80 children and 400 adults were selected at random from the Israeli national serum bank. The sera was obtained in 2002 and in 2007, two time points that followed a major drift in the infectious H3N2 influenza virus strain (A/Panama/2007/99 to A/Wisconsin/67/2005).ResultsIn the summer of 2002, 13% of the children had Hemagglutination Inhibition (HI) antibody titers of at least 40 and these antibodies recognized both A/Panama/2007/99 and A/Wisconsin/67/2005, where the latter strain only began to circulate in Israel in 2006. In 2007, 29% of the children had HI antibody titers of at least 40 directed against both A/Wisconsin/67/2005 and A/Panama/2007/99, even though they had never been exposed to the latter virus. Anti-A/Panama/2007/99 antibodies were detected in 58% and 68% of the 2002 and 2007 adult samples, respectively, while 8% and 39% had antibodies against A/Wisconsin/67/2005, respectively.ConclusionsThe presence of naturally occurring cross-reactive influenza virus antibodies in a significant percentage of children has important implications for the development of a universal influenza vaccine.

Herpes zoster in a partially vaccinated pediatric population in central Israel.

Background: This study was performed during an era of partial vaccination with varicella vaccine in Israel to characterize ambulatory pediatric herpes zoster (HZ) cases in a population with partial varicella vaccination coverage. Methods: Data were collected from computerized databases of a population of 114,000 children. Records of children aged 0–18 years, diagnosed with HZ during 2006 to 2008 were reviewed by pediatric infectious diseases experts. Telephone interviews were done with a sample of the parents to get further clinical details. Results: Of 692 medical records reviewed, 450 cases were approved for analysis, and 77 interviews were conducted. Incidence of HZ was 130 of 100,000 person life-years. Peak incidence was detected in children aged 9–11 years (222/100,000 person life-years). Pain and fever accompanied 52% and 13% of episodes, respectively. Higher risk for HZ was found in children who had varicella during their first year of life (relative risk and 95% confidence interval: 13.5[9.6–18.8]; P < 0.001), and in children who had varicella during the second year of life (relative risk = 2 [1.5–2.6]; P < 0.001). Vaccination was found to be protective against HZ (relative risk = 0.42 [0.33–0.55]; P < 0.001). Conclusions: The epidemiology of HZ seems to be changing in a population with partial varicella vaccination rate. Our results may suggest that children who contracted chicken pox in their first year of life may benefit from varicella vaccination.

Epidemiological and Virological Characterization of Influenza B Virus Infections.

While influenza A viruses comprise a heterogeneous group of clinically relevant influenza viruses, influenza B viruses form a more homogeneous cluster, divided mainly into two lineages: Victoria and Yamagata. This divergence has complicated seasonal influenza vaccine design, which traditionally contained two seasonal influenza A virus strains and one influenza B virus strain. We examined the distribution of the two influenza B virus lineages in Israel, between 2011–2014, in hospitalized and in non-hospitalized (community) influenza B virus-infected patients. We showed that influenza B virus infections can lead to hospitalization and demonstrated that during some winter seasons, both influenza B virus lineages circulated simultaneously in Israel. We further show that the influenza B virus Yamagata lineage was dominant, circulating in the county in the last few years of the study period, consistent with the anti-Yamagata influenza B virus antibodies detected in the serum samples of affected individuals residing in Israel in the year 2014. Interestingly, we found that elderly people were particularly vulnerable to Yamagata lineage influenza B virus infections.

The dynamics of infection and the persistence of immunity to A(H1N1)pdm09 virus in Israel

Influenza virus A(H1N1)pdm09 first appeared in Israel in late April 2009, disappeared in mid‐March 2010, and reappeared in late October 2010. Symptoms were mostly mild without need for medical care.

Prehypertension among 2.19 million adolescents and future risk for end-stage renal disease

Objective: Persistent hypertension in adulthood is a leading cause of end-stage renal disease (ESRD). Whether lower blood pressure (BP) values, in the range of prehypertension, are also associated with future occurrence of ESRD is unclear. Even less clear is the potential risk of early prehypertension appearing in adolescence. To address this question, we examined whether BP measurements in the prehypertensive range at age 16–19 years predict adult ESRD. Methods: Medical data on 2194 635 16–19-year-old adolescents examined for medical fitness prior to military service from 1977 to 2013 were linked to the Israeli ESRD registry in this nationwide population-based cohort study. Incident cases of ESRD were recorded. Survival models were applied. Results: During 35 007 506 person-years of follow-up (median follow-up 16.8 years), there were 690 ESRD cases, with an overall incidence rate of 1.97 cases per 100 000 person-years. Examinees with elevated BP readings in the prehypertensive range (BP between the 90th and 95th percentiles or between 120 and 139/80–89 mmHg) had increased incidence of ESRD with a hazard ratio of 1.32 (95% confidence interval, 1.11–1.58) adjusted for year of birth, age at examination, sex, BMI, education, socioeconomic status, and country of origin. Hypertension (BP above the 95th percentile or above 140/90 mmHg) was associated with a hazard ratio of 1.44 (95% confidence interval, 1.17–1.79). A spline model demonstrated a nadir of risk at SBP values as low as 94 mmHg. Conclusion: Asymptomatic, healthy adolescents with prehypertension have a 32% increased risk for subsequent ESRD, compared with adolescents with optimal BP.

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.

Adolescent BMI at Northern Israel: From Trends, to Associated Variables and Comorbidities, and to Medical Signatures.

AbstractThe increasing prevalence of abnormal body mass index (BMI), mainly obesity, is becoming a significant public health problem. This cross-sectional study aimed to provide a comprehensive view of secular trends of BMI, and the associated socio-demographic variables and comorbidities among adolescents with abnormal BMI. Individuals of the study population were born mainly between 1970 and 1993, and were examined at 16 to 19 years of age during the years 1987 to 2010, at 1 conscription center in the northern district of Israel.The study population included 113,694 adolescents. Univariate and multivariable logistic regression models were used to investigate the associations between BMI categories, socio-demographic variables, and medical conditions.A downward trend in the prevalence of normal BMI among both male and female adolescents was obtained, while trends of overweight and obesity (in both genders) and underweight (only among females) rose. Socio-demographic variables such as religion, education, family-related parameters, residential environment, country of birth, and origin were all associated with different risks for abnormal BMI. Obesity was associated with higher risk for hyperlipidemia, endocrine disorders (only in males), knee disorders, and hypertension type I + II (in both genders). Overweight was associated with knee disorders (only in females). Underweight, exclusively in males, was associated with increased risk for endocrine disorders, proteinuria, and cardiac disorders. Hierarchical clustering analysis revealed the intricate relations between gender, BMI, and medical signatures. It brought to light novel clusters of diseases that were abundant among populations having above-normal BMI or underweight males. Furthermore, above-normal BMI was associated with a lower rate of cardiac anomalies and scoliosis/kyphosis, whereas being underweight was associated with a lower risk for hypertension and flat foot.This study provides a reliable and in-depth view of secular trends in height, weight, and BMI of male and female adolescents. It supports previous associations between abnormal BMI and demographic variables and comorbidities, while uncovering novel associations, mainly regarding medical signatures of each gender–BMI group. This might lead to better monitoring, early detection, prevention, and treatment of various conditions associated to abnormal BMI categories and gender groups.