Recent trends in the epidemiology of non-typhoidal Salmonella in Israel, 1999-2009.

The aim of the present study was to assess the recent trends in the epidemiology of non-typhoid Salmonella in Israel using a sentinel laboratory-based surveillance network. Between 1999 and 2009, 8758 Salmonella stool isolates were reported by five sentinel laboratories. There was a significant decrease in the incidence rate of Salmonella isolates from 70·5/100,000 in 1999 to 21·6/100,000 in 2005 followed by a slight increase to 30·3/100,000 in 2009. Of all Salmonella, 64·3% were isolated from children in the 0-4 years age group. Up to 2008, S. Enteritidis was the most prevalent serotype and in 2009 S. Infantis emerged as the most common Salmonella serotype. The decrease in the incidence of S. Enteritidis and S. Typhimurium and increase in S. Infantis among humans were associated with a similar trend among breeding flocks, which followed significant preventive interventions conducted against S. Enteritidis and S. Typhimurium infections in poultry. Tight surveillance and education of food handlers and consumers should be enhanced to reduce the foodborne transmission of Salmonella in Israel.

Curtailed short-term and long-term survival following infection with non-typhoid Salmonella in Israel.

Among bacterial foodborne pathogens, non-typhoid Salmonella enterica (NTS) is a leading cause of death worldwide. This study assessed short-term and long-term mortality following NTS infection in Israel, and evaluated the effects of age, sex, source of isolation and different serotypes on mortality. The source of data was a national registry of NTS isolates submitted to the Salmonella Reference Center, Government Central Laboratories, in Jerusalem, Israel, during 1997-2006. Vital status was derived from the registry of the Israeli Ministry of the Interior. The survival of a cohort of 15,919 patients infected with the top five NTS serotypes was evaluated by calculating age-standardized mortality ratios (SMRs) and by Cox proportional hazards multivariate regressions at three follow-up time intervals: 30 days, 1 year and end of follow-up. The median follow-up time was 6.44 years (mean, 6.21 years; range, 1 day to 10.80 years). The cumulative crude mortality rates at the three time intervals were 0.68%, 1.86% and 4.40%, respectively, corresponding to increased SMRs of 16.95 (95% CI 13.9-20.46), 4.25 (95% CI 3.78-4.76), and 1.83 (95% CI 1.70-1.97), respectively. Cox regressions revealed that increasing age, extraintestinal source of isolation and NTS serotype had significant effects on mortality within all three follow-up intervals. The risk of mortality was increased for serotypes Infantis and Typhimurium, and decreased for serotypes Virchow and Hadar, as compared with serotype Enteritidis. The study revealed curtailed short-term and long-term survival following NTS infection that persisted for many years following detection by culture.

A Middle East subregional laboratory-based surveillance network on foodborne diseases established by Jordan, Israel, and the Palestinian Authority.

In late 2002, health professionals from the ministries of health and academia of Jordan, the Palestinian Authority and Israel formed the Middle East Consortium on Infectious Disease Surveillance (MECIDS) to facilitate trans-border cooperation in response to infectious disease outbreaks. The first mission of MECIDS was to establish a regional, laboratory-based surveillance network on foodborne diseases. The development of harmonized methodologies and laboratory capacities, the establishment of a common platform of communication, data sharing and analysis and coordination of intervention steps when needed were agreed upon. Each of the three parties selected the microbiological laboratories that would form the network of sentinel laboratories and cover the different districts of each country and also designated one laboratory as the National Reference Laboratory (NRL). Data analysis units have been established to manage the data and serve as a central point of contact in each country. The MECIDS also selected a regional data analysis unit, the Cooperative Monitoring Centre (CMC) located in Amman, Jordan, and established a mechanism for sharing data from the national systems. Joint training courses were held on interventional epidemiology and laboratory technologies. Data collection started in July 2005 with surveillance of salmonellosis as the first target. This network of collaboration and communication established in an area of continuous dispute represents an important step towards assessing the burden of foodborne diseases in the region and is expected to be fundamental for coordination of public health interventions and prevention strategies.

Extended-spectrum beta-lactamase-producing Shigella strains in Israel, 2000-2004.

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.

Prevalence and correlates of diphtheria toxoid antibodies in children and adults in Israel.

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, 3,185 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 or=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.

Salmonella enterica serotype Virchow: epidemiology, resistance patterns and molecular characterisation of an invasive Salmonella serotype in Israel.

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 <1 year (4.4/100,000). Only 6% of isolates were susceptible to all ten antibiotic agents tested; 34% were resistant to one agent, 54% to one to three agents, and 40% to four to six agents. A high proportion of the tested isolates were resistant to nalidixic acid (89%), streptomycin (56%), tetracycline (43%), trimethoprim-sulphamethoxazole (38%) and chloramphenicol (28%), but none to ciprofloxacin or ceftriaxone. Pulsed-field gel electrophoresis revealed two closely related clusters, each containing a predominant pulsotype. Coupled with its invasive propensity, the increasing incidence of highly resistant S. Virchow in Israel is of real concern. Future research should focus on the sources of S. Virchow in the food chain in order to institute effective control measures.

Antimicrobial resistance of Shigella flexneri serotypes in Israel during a period of three years: 2000-2002.

This is a surveillance study of the antimicrobial resistance of the S. flexneri group in the context of its serotype diversity. It includes 1422 isolates, which were sent to the National Shigella Reference Centre (NSRC) by hospitals and outpatient clinics in Israel during a 3-year period (2000-2002). The strains were identified and classified according to the prevalence and antigenic structure of their serotypes. All samples were checked for resistance to ampicillin (AMP), trimethoprim-sulphamethoxazole (TMP-SMX), ceftriaxone (CRO), tetracycline (TE), nalidixic acid (NAL), and chloramphenicol (C) by the disk diffusion method of Bauer et al. There were significant differences in their resistance to the individual antimicrobials with resistance to AMP, TE and C being lower among the strains of serotype 6 than among those of serotypes 2a and 1b. The resistant phenotypes were also serotype-specific. The similarities both in individual and in phenotype resistance between the rare and the prevalent serotypes (but not serotype 6) may be attributed to their antigenic relatedness. The serospecificity of the antimicrobial resistance was not affected by external factors such as seasonality and source (hospital or outpatient laboratory) of the isolates, and the age and sex of the patients. The serotype-specific approach can assist in properly assessing the problem of the antimicrobial resistance of the Shigella flexneri group and may prove useful for the empirical therapy of shigellosis. The observed interdependency between resistance and the antigenic specificity and relatedness of the S. flexneri serotypes requires additional investigation.

Traveling waves and the processing of weakly tuned inputs in a cortical network module.

Recent studies have shown that local cortical feedback can have an important effect on the response of neurons in primary visual cortex to the orientation of visual stimuli. In this work, we study the role of the cortical feedback in shaping the spatiotemporal patterns of activity in cortex. Two questions are addressed: one, what are the limitations on the ability of cortical neurons to lock their activity to rotating oriented stimuli within a single receptive field? Two, can the local architecture of visual cortex lead to the generation of spontaneous traveling pulses of activity? We study these issues analytically by a population-dynamic model of a hypercolumn in visual cortex. The order parameter that describes the macroscopic behavior of the network is the time-dependent population vector of the network. We first study the network dynamics under the influence of a weakly tuned input that slowly rotates within the receptive field. We show that if the cortical interactions have strong spatial modulation, the network generates a sharply tuned activity profile that propagates across the hypercolumn in a path that is completely locked to the stimulus rotation. The resultant rotating population vector maintains a constant angular lag relative to the stimulus, the magnitude of which grows with the stimulus rotation frequency. Beyond a critical frequency the population vector does not lock to the stimulus but executes a queasi-periodic motion with an average frequency that is smaller than that of the stimulus. In the second part we consider the stable intrinsic state of the cortex under the influence of isotropic stimulation. We show that if the local inhibitory feedback is sufficiently strong, the network does not settle into a stationary state but develops spontaneous traveling pulses of activity. Unlike recent models of wave propagation in cortical networks, the connectivity pattern in our model is spatially symmetric, hence the direction of propagation of these waves is arbitrary. The interaction of these waves with an external-oriented stimulus is studied. It is shown that the system can lock to a weakly tuned rotating stimulus if the stimulus frequency is close to the frequency of the intrinsic wave.

Proteases of Treponema denticola outer sheath and extracellular vesicles.

Electron microscopical observations of the oral periodontopathogen Treponema denticola show the presence of extracellular vesicles bound to the bacterial surface or free in the surrounding medium. Extracellular vesicles from T. denticola ATCC 35404, 50 to 100 nm in diameter, were isolated and further characterized. Protein and proteolytic patterns of the vesicles were found to be very similar to those of isolated T. denticola outer sheaths. They were enriched with the major outer sheath polypeptides (molecular sizes, 113 to 234 kDa) and with outer sheath proteases of 91, 153, 173, and 228 kDa. These findings indicate that treponemal outer sheath vesicles contain the necessary adhesins and proteolytic arsenal for adherence to and damage of eucaryotic cells and mammalian matrix proteins. The major outer sheath- and vesicle-associated protease of T. denticola ATCC 35404 was purified and characterized. The purified enzyme had a molecular size of 91 kDa, and it dissociated into three polypeptides of 72, 38, and 35 kDa upon heating in the presence of sodium dodecyl sulfate with or without a reducing agent. The activity of the enzyme could be inhibited by diisopropylfluorophosphate, phenylmethylsulfonyl fluoride, and phenylboronic acid. The value of the second-order rate constant of the protease inactivation by phenylmethylsulfonyl fluoride was 0.48 x 10(4) M(-1) min-1. Inhibition of the enzyme by phenylboronic acid was rapid (< 1 min) and pH dependent. These data strongly suggest that this major surface proteolytic activity belongs to a family of serine proteases.

Theory of orientation tuning in visual cortex.

The role of intrinsic cortical connections in processing sensory input and in generating behavioral output is poorly understood. We have examined this issue in the context of the tuning of neuronal responses in cortex to the orientation of a visual stimulus. We analytically study a simple network model that incorporates both orientation-selective input from the lateral geniculate nucleus and orientation-specific cortical interactions. Depending on the model parameters, the network exhibits orientation selectivity that originates from within the cortex, by a symmetry-breaking mechanism. In this case, the width of the orientation tuning can be sharp even if the lateral geniculate nucleus inputs are only weakly anisotropic. By using our model, several experimental consequences of this cortical mechanism of orientation tuning are derived. The tuning width is relatively independent of the contrast and angular anisotropy of the visual stimulus. The transient population response to changing of the stimulus orientation exhibits a slow "virtual rotation." Neuronal cross-correlations exhibit long time tails, the sign of which depends on the preferred orientations of the cells and the stimulus orientation.