Trends in the Epidemiology of Campylobacteriosis in Israel (1999-2012).

The objective of this study was to examine the recent trends in the epidemiology of campylobacteriosis in Israel. A Sentinel Laboratory-Based Surveillance Network for Bacterial Enteric Diseases was established in Israel by the Israel Center for Disease Control (ICDC). This network generated data on subjects from whom Campylobacter spp. was isolated in community and hospital laboratories. Further characterization of the isolates was done at the Campylobacter National Reference Laboratory. Data from these two sources were integrated and analyzed at the ICDC. Between 1999 and 2012, 40,978 Campylobacter stool isolates were reported to the ICDC by the sentinel laboratories. The incidence rate of campylobacteriosis increased from 65.7 per 100,000 in 1999 to 101.7 per 100,000 in 2012. This increase resulted from a significant rise in the incidence of campylobacteriosis in the Jewish population which, since 2009, surpassed the consistent higher incidence of the disease in Israeli Arabs. The peak morbidity in Israel consistently occurred in late spring, with a risk excess in males compared with females, in younger age groups and earlier in the life span among Arabs than among Jews and others. These results suggest that further analytical studies should be carried out to identify risk factors responsible for the increased incidence of campylobacteriosis and better direct prevention and control of the disease in Israel.

Comparative analysis of homocysteine concentrations in patients with retinal vein occlusion versus thrombotic and atherosclerotic disorders.

The objectives of the present study were to determine the concentrations of plasma homocysteine in a large (n = 562) cohort of patients with retinal vein occlusion (RVO) and to compare them with the values observed in other vascular thrombotic and atherosclerotic conditions. Results were compared with those observed in patients with deep vein thrombosis (n = 1700), pulmonary embolism (n = 542), transient ischemic attack (n = 1301), cerebrovascular accident (n = 1299), myocardial infarction (n = 3087), as well as peripheral artery occlusive disease (n = 1946). No differences were found between the age-adjusted estimated marginal mean +/- SE for homocysteine concentrations in individuals with RVO and in those who had other atherosclerotic and atherothrombotic diseases The respective concentrations for RVO, deep vein thrombosis, pulmonary embolism, transient ischemic attack, cerebrovascular accident, myocardial infarction, and peripheral artery occlusive disease were 13.8 +/- 0.4, 14.7 +/- 0.3, 14.3 +/- 0.5, 14.2 +/- 0.3,14.6 +/- 0.3, 13.8 +/- 0.2, 14.4 +/- 0.2 pmol/l for men and 11.4 +/- 0.4, 10.7 +/- 0.2, 10.8 +/- 0.3, 10.8 +/- 0.2, 11.8 +/- 0.2, 11.2 +/- 0.2 pmol/l for women. In conclusion, the concentrations of homocysteine observed in patients with RVO are similar to those detected in other thrombotic and atherosclerotic vascular disorders. In view of the fact that this is a common disorder of the elderly, increased homocysteine concentrations often reported in patients with RVO could reflect the underlying atherothrombotic condition and might not necessarily be specifically related to the RVO per se. This information is relevant in researching the potential etiopathologic role, if any, of increased homocysteine concentrations in RVO.

A single testing of serum amyloid a levels as a tool for diagnosis and treatment dilemmas in familial Mediterranean fever.

OBJECTIVES: In a significant proportion of patients with familial Mediterranean fever (FMF), serum amyloid A (SAA) remains elevated during attack-free periods, thereby increasing the risk of developing amyloidosis. The aim of the study was to determine various correlates of elevated SAA and evaluate the role of SAA measurement in the diagnosis and management of FMF. METHODS: We reviewed the medical files of all 204 patients from our FMF center in whom SAA measurements were performed. SAA levels and the resulting diagnostic and therapeutic decisions were analyzed in relation to the reasons of SAA testing and to several clinical and genetic parameters. RESULTS: SAA measurements were made for diagnostic purposes in 29% of the patients. In the remainder, SAA measurements were used for adjustment of colchicine dose. Elevated SAA levels are found in a third of FMF patients during an attack-free period. The highest rate of elevated SAA levels was found in patients with proteinuria (60% of this patient group), followed by noncompliant (40%) and genetically positive asymptomatic patients (38%). Elevated SAA levels during remission were associated with family history of FMF, M694V homozygosity, and elevated C-reactive protein (CRP) (P<0.05 for each). Patients homozygous for the M694V mutation had the highest level of SAA. SAA measurement led to a change in colchicine dose in 30% of the patients, predominantly in noncompliant patients and patients with proteinuria or with atypical manifestations. CONCLUSIONS: Measurement of SAA level may help in the diagnosis of FMF and in adjustment of the colchicine dose.

Chemiluminescent analysis of light-irradiated leukocytes as a diagnostic tool for fast identification of pathological states.

OBJECTIVE: Reactive oxygen species (ROS), mainly produced by polymorphonuclear neutrophils (PMN), are a significant part of host defense in pathologic states. We attempted to relate numbers of PMN and ROS generated within PMN to develop an alternative photochemical approach for evaluation of the potential of these cells to resist the development of inflammatory pathology. BACKGROUND DATA: Lack of sensitivity to light has been reported in healthy cells, while sensitivity to light characterizes cell pathology. METHODS: Human leukocytes from 34 donors were isolated and irradiated with a non-laser blue light (2 and 5 mW/cm(2) for 2 minutes), and a luminol-dependent chemiluminescence assay that reflects intracellular production of ROS was applied thereafter. The levels of basal chemiluminescence (BCL) were related to respective numbers of PMN. RESULTS: A light-insensitive cluster was discovered within the total sample and was considered to be a discrete nonpathological group. Following elimination of this group, the rest of the sample was divided into three well-defined light-sensitive groups, which were attributed to various pathological states, and differed in PMN numbers and BCL counts. Within these groups the two traits were interrelated, and each PMN range was associated with a respective level of intracellular ROS. CONCLUSIONS: Leukocyte responsiveness to light can be used for discrimination between pathological and nonpathological states and prognostic evaluation of pathological development. Patients exhibiting similar clinical symptoms could be divided into separate groups with potentially different outcomes. A novel definition of nonpathological states as well as the mechanism underlying the bell-shaped curve that delineates the relationship between PMN number and intracellular ROS is suggested in pathological states.

Risk Factors for Sporadic Infection With Campylobacter Spp. Among Children in Israel: A Case-control Study.

BACKGROUND: Campylobacter spp. has been identified as one of the leading causes of bacterial gastroenteritis in the world. In recent years, an increase in the incidence of campylobacteriosis in several countries, including Israel, was demonstrated. The incidence rate of campylobacteriosis in Israel increased from 22.3 per 100,000 in 1997 to 77.4 per 100,000 in 2009. The aim of this study was to explore risk factors for sporadic infection with Campylobacter among young children in Israel. METHODS: A matched case-control study was performed to investigate risk factors for sporadic Campylobacter infection among 113 affected children of 1-5 years of age and 113 age-matched, gender-matched and neighborhood-matched controls. Information about exposure to potential risk factors was obtained via telephone interview and was evaluated by conditional logistic regression analysis. RESULTS: In the multivariable model, for each additional chicken meal consumed during the week before the onset of illness, the odds for Campylobacter infection increased by 32% [adjusted matched odds ratios (aMOR): 1.32; 95% confidence interval (CI): 1.01-1.72; P = 0.04], whereas consumption of fruits and vegetables decreased the odds for Campylobacter infection by 97% (aMOR: 0.03; 95% CI: 0.00-0.28; P < 0.01), and for each additional child living in the household, the odds for infection decreased by 48% (aMOR: 0.52; 95% CI: 0.33-0.83; P < 0.01). Using diaper increased the odds for campylobacteriosis (aMOR: 7.36; 95% CI: 1.66-32.70; P < 0.01). CONCLUSIONS: Interventions that focus on proper handling of chicken and chicken products, hand washing and encouraging consumption of fruits and vegetables could help in controlling Campylobacter infections.

Monitoring oral anticoagulant therapy by telephone communication.

The number of patients who need supervision during oral anticoagulant treatment is growing constantly. We have presently enrolled 156 patients who were referred to our anticoagulant clinic and who were taking sodium warfarin with target International Normalized Ratios (INR) of low (2-3), intermediate (2.5-3.5) and high (3-4) range. Patients performed the tests in laboratories situated in locations at their convenience and received further instructions from a specialist via telephone communication. A total of 8758 prothrombin times (5214, 1947 and 1597 tests for individuals in the low, intermediate and high range, respectively) were performed over the period of 3.16 +/- 2.6 years (range, 6 months-9.5 years) and reported to the specialist. It was found that in the aforementioned three groups of intensity 63.3, 57.0 and 47.7% of the INRs were within the target range, the respective percentages for the expanded (+/- 0.5) target INR being 92.8, 87.8 and 78.5%. The INTERDAY software was used to calculate the number and proportion of days within the target INR range, the respective results being 71.0, 64.0 and 51.6% and 96.2, 93.2, 86.4% for the expanded range. The number and percentage of bleeding and embolic complications' referrals to the emergency room and hospitalizations were similar to those reported for anticoagulant clinics in which patients have to actually pay a personal visit in order to receive instructions. Our study is significant in that it documents that trans-telephonic communication is feasible safe and cost-effective and that the clinical results are at least as good as those obtained by traditional consultation.

Nasopharyngeal carriage of Streptococcus pneumoniae by adults and children in community and family settings.

The rate of Streptococcus pneumoniae carriage among adults was compared with that among children (age, < or =6 years) in the same population. Nasopharyngeal culture results for 1300 adults and 404 children were analyzed. S. pneumoniae was carried by only 4% of the adults, compared with 53% of children in the same community. Young age, day care center attendance, having young siblings, and no antibiotic use during the month before screening were associated with the high carriage rate among children, whereas the only risk factor associated with carriage among adults was the presence of a respiratory infection on the screening day. S. pneumoniae serotype distribution and antibiotic resistance patterns differed between adults and children. Isolates of the same serotype--even of the same clone--differed in their antibiotic susceptibility patterns between children and adults. In a subanalysis of 151 pairs of children and their parents and of 32 pairs of siblings, intrafamilial transmission of S. pneumoniae could not be demonstrated.

Association between carriage of Streptococcus pneumoniae and Staphylococcus aureus in Children.

CONTEXT: Widespread pneumococcal conjugate vaccination may bring about epidemiologic changes in upper respiratory tract flora of children. Of particular significance may be an interaction between Streptococcus pneumoniae and Staphylococcus aureus, in view of the recent emergence of community-acquired methicillin-resistant S aureus. OBJECTIVE: To examine the prevalence and risk factors of carriage of S pneumoniae and S aureus in the prevaccination era in young children. DESIGN, SETTING, AND PATIENTS: Cross-sectional surveillance study of nasopharyngeal carriage of S pneumoniae and nasal carriage of S aureus by 790 children aged 40 months or younger seen at primary care clinics in central Israel during February 2002. MAIN OUTCOME MEASURES: Carriage rates of S pneumoniae (by serotype) and S aureus; risk factors associated with carriage of each pathogen. RESULTS: Among 790 children screened, 43% carried S pneumoniae and 10% carried S aureus. Staphylococcus aureus carriage among S pneumoniae carriers was 6.5% vs 12.9% in S pneumoniae noncarriers. Streptococcus pneumoniae carriage among S aureus carriers was 27.5% vs 44.8% in S aureus noncarriers. Only 2.8% carried both pathogens concomitantly vs 4.3% expected dual carriage (P =.03). Risk factors for S pneumoniae carriage (attending day care, having young siblings, and age older than 3 months) were negatively associated with S aureus carriage. CONCLUSIONS: Streptococcus pneumoniae carriage, specifically of vaccine-type strains, is negatively associated with S aureus carriage in children. The implications of these findings in the pneumococcal vaccine era require further investigation.

Positive tissue transglutaminase antibodies with negative endomysial antibodies: low rate of celiac disease.

BACKGROUND: Screening for celiac disease is based on the sequential evaluation of serologic tests and intestinal biopsy; an optimal screening protocol is still under investigation. The screening policy of one of the main healthcare providers in Israel (Maccabi) consists of measuring total immunoglobulin A and tissue transglutaminase IgA antibodies and confirming positive results by endomysial antibodies. For IgA-deficient patients antigliadin IgG is measured. OBJECTIVES: To evaluate the use of tTGA as a first-level screening test in patients suspected of having celiac disease METHODS: The results of tTGA and EMA tests over a 3 month period were obtained from the laboratory computer. Letters were sent to the referring physicians of patients with positive tests, requesting clinical information and small intestinal biopsy results. tTGA was performed using an anti-guinea pig tTG-IgA enzyme-linked immunosorbent assay kit. RESULTS: Overall, 2,505 tTGA tests were performed: 216 (8.6%) were tTGA-positive of which 162 (75%) were EMA-negative (group 1) and 54 (25%) EMA-positive (group 2.) Clinical information was obtained for 91 patients in group 1 and 32 in group 2. Small intestinal biopsy was performed in 33 (36%) and 27 patients (84%) in groups 1 and 2, respectively. Celiac disease was diagnosed in 4 biopsies (12%) in group 1 and 23 (85%) in group 2 (P < 0.0001). The positive predictive value was 45% for tTGA and 85% for EMA. CONCLUSIONS: Symptomatic patients with positive tTGA and negative EMA have a low rate of celiac disease compared to those who are tTGA-positive and EMA-positive. Confirmation with EMA is advised when tTGA is performed as a first-level screening for suspected celiac disease.

Pregnancy outcomes in women with severe hypothyroidism.

OBJECTIVE: Hypothyroidism during pregnancy has been associated with adverse obstetrical outcomes. Most studies have focused on subjects with a mild or subclinical disorder. The aims of the present study were to determine the relative rate of severe thyroid dysfunction among pregnant women with hypothyroidism, identify related factors and analyse the impact on pregnancy outcomes. DESIGN: A retrospective case series design was employed. METHODS: The study group included 101 pregnant women (103 pregnancies) with an antenatal serum TSH level >20.0 mIU/l identified from the 2009-2010 computerised database of a health maintenance organisation. Data were collected from the medical records. Pregnancy outcomes were compared with those of a control group of 205 euthyroid pregnant women during the same period. RESULTS: The study group accounted for 1.04% of all insured pregnant women with recorded hypothyroidism during the study period. Most cases had an autoimmune aetiology. All women were treated with levothyroxine (L-T4) during pregnancy. Maximum serum TSH level measured was 20.11-150 mIU/l (median 32.95 mIU/l) and median serum TSH level 0.36-75.17 mIU/l (median 7.44 mIU/l). The mean duration of hypothyroidism during pregnancy was 21.2 ± 13.2 weeks (median 18.5 weeks); in 36 cases (34.9%), all TSH levels during pregnancy were elevated. Adverse pregnancy outcomes included abortions in 7.8% of the cases, premature deliveries in 2.9% and other complications in 14.6%, with no statistically significant differences from the control group. Median serum TSH level during pregnancy was positively correlated with the rate of abortions+premature deliveries and rate of all pregnancy-related complications (P<0.05). CONCLUSIONS: Abortions and premature deliveries occur infrequently in women with severe hypothyroidism. Intense follow-up and L-T4 treatment may improve pregnancy outcomes even when target TSH levels are not reached.

Streptococcus pneumoniae carriage in the Gaza strip.

BACKGROUND: Pneumococcal infections cause major morbidity and mortality in developing countries. We report the epidemiology of S. pneumoniae carriage in a developing region, the Gaza strip, and evaluate the theoretical coverage of carriage strains by pneumococcal conjugate vaccines (PCVs). METHODOLOGY: In 2009 we conducted a cross-sectional survey of S. pneumoniae carriage in healthy children and their parents, living throughout the Gaza strip. Data were collected and nasopharyngeal swabs were obtained. Antibiotic susceptibilities were determined by Vitek-2 and serotypes by the Quellung reaction. PRINCIPAL FINDINGS: S. pneumoniae carriage was detected in 189/379 (50%) of children and 30/376 (8%) of parents. Carriage prevalence was highest in children <6 months of age (63%). Significant predictors for child carriage were number of household members and DCC attendance. The proportion of pediatric and adults isolates with serotypes included in PCV7 were 32% and 20% respectively, and 46% and 33% in PCV13 respectively. The most prominent non-vaccine serotypes (NVT) were 35B, 15B/C and 23B. Penicillin-nonsusceptible strains were carried by 70% of carriers, penicillin-resistant strains (PRSP) by 13% and Multi-drug-resistant (MDR) by 30%. Of all PRSP isolates 54% belonged to serotypes included in PCV7 and 71% in the PCV13. Similarly, 59% and 73% of MDR-SP isolates, would theoretically be covered by PCV7 and PCV13, respectively. CONCLUSIONS: This study demonstrates that, PCV13-included strains were carried by 46% and 33% of pediatric and adult subjects respectively. In the absence of definitive data regarding the virulence of the NVT strains, it is difficult to predict the effect of PCVs on IPD in this region.

Positive deamidated gliadin peptide antibodies and negative tissue transglutaminase IgA antibodies in a pediatric population: to biopsy or not to biopsy.

Reports from our clinical laboratory database show that 75% of children <2 years old tested for celiac serology who were found positive for deamidated gliadin peptide (DGP) antibodies had negative results for tissue transglutaminase IgA. DGP levels were shown to decline and disappear without a gluten-free diet. This observation questions DGP's specificity for diagnosis of celiac disease.

Performance of serology assays for diagnosing celiac disease in a clinical setting.

Diagnosis of celiac disease frequently depends upon serology assays. We set out to prospectively assess the diagnostic value of five serology tests: an enzyme-linked immunosorbent assay (ELISA) for tissue transglutaminase (tTG)-immunoglobulin A (IgA) and tTG-IgG, a chemiluminescence assay for tTG-IgA, an ELISA for deamidated gliadin peptide (DGP) IgG and IgA screening, and detection of endomysial antibodies (Abs) by indirect immunofluorescence. One hundred sixteen children at high risk for developing celiac disease were evaluated clinically and underwent small bowel biopsies and blood serology tests. We examined differences between younger and older children in terms of clinical presentation, test performance, and the ability of high Ab levels to correctly predict diagnosis of celiac disease. Celiac disease was diagnosed for 85 (73%) children. No significant clinical differences were observed between the biopsy-positive and biopsy-negative groups. Children < or = 3 years of age revealed higher concentrations of tTG-IgA and DGP Abs than children >3 years old (P = 0.017 and 0.007, respectively). High Ab concentrations were predictive of villous atrophies, with sensitivities ranging from 92.8% to 97.9%, depending on the assay and the cutoff points applied. Sensitivities, specificities, positive predictive values, and negative predictive values varied among assays and improved after correction for best cutoff points. Assay specificities obtained in the clinical setting were lower than expected. The new tTG-IgA chemiluminescence assay demonstrated high throughput but low specificity (74.2%). The tTG-IgA ELISA exhibited the highest test efficiency, and the tTG-IgA chemiluminescence assay was suitable for large-scale screening, with reduced specificity. High concentrations of celiac disease-specific Abs bring into question the need for performance of biopsies on children at high risk.

Parental Staphylococcus aureus carriage is associated with staphylococcal carriage in young children.

BACKGROUND: Staphylococcus aureus colonization typically precedes infection but risk factors for colonization in children are not well defined. Our previous study suggested that S. aureus carriage in children is associated with parental carriage. Here we wished to distinguish the different components that play a role in the risk to a child of a S. aureus-carrying parent. METHODS: Between 2002 and 2005, children (0-40 months) and their parents were screened for carriage of S. aureus and Streptococcus pneumoniae during 1 of 6 surveys. Data were collected from the parents and the medical files. Multivariate analysis of possible associated factors and effect modifiers was carried out. Pulse-field gel electrophoresis was performed to determine strain relatedness. RESULTS: A total of 4648 children were screened. S. aureus was isolated from 342 (7.6%) children and 992 (22%) parents. Pairs of parent-child carriers were found in 155 cases, over twice the rate expected by chance (1.66%, P<0.0001). The variable that was most significantly associated with carriage in children was having a parent carrier (OR: 3.35; 95% CI: 2.59-4.33), whereas close contact with peers (as assessed by day care centers attendance or having young siblings) was not associated with carriage. Children<3 months had the highest carriage rate and children aged 6 to 12 months had the lowest (25.4% and 4.3%, respectively, P<0.0001). Breast-feeding was not associated with higher or lower carriage. In 30 of 150 strains studied, >70% parent-child strains were genetically identical. CONCLUSIONS: Parental S. aureus colonization, but not DCC attendance or having young siblings, is an independent predictor for staphylococcal carriage in young children.

Independent risk factors for carriage of penicillin-non-susceptible Streptococcus pneumoniae.

Antibiotic treatment, day-care center (DCC) attendance and young age are associated with penicillin-non-susceptible Streptococcus pneumoniae (PNSSp) carriage. Yet, it is unclear whether each is an independent risk factor for the individual. This cross-sectional surveillance study was designed to answer this question. Nasopharyngeal cultures were obtained from 429 children (< 6 y) during a visit to the pediatrician's office. Two risk rates were calculated: the individual's absolute risk to carry PNSSp [simple odds ratio (ORS)] and the risk of an individual who is already a carrier [conditional odds ratio (ORC)]. Streptococcus pneumoniae was isolated from 52.7% of 401 children. PNSSp was detected in 37.1% of carriers. Independent risk factors were: young age [ORS 2.24, 95% confidence interval (95% CI) 1.2-4.2], DCC attendance (ORS 3.8, 95% CI 1.9-7.5), having young siblings (ORS 2.3, 95% CI 0.95-5.57) and each antibiotic treatment during the previous 3 months (ORS 1.5, 95% CI 1.25-1.85). The only significant risk factor among carriers was prior antibiotic treatment (ORC 2.24, 95% CI 1.64-3.05). Young children, who attended DCC and received 1 antibiotic course (9% of the population) had a risk 12.9 times higher than children without these features.