A Randomized Controlled Study Assessing Convalescent Immunoglobulins vs Convalescent Plasma for Hospitalized Patients With Coronavirus 2019.

BACKGROUND: It is unknown whether convalescent immunoglobulins (cIgGs) are better than convalescent plasma (CP) for patients with coronavirus 2019 (COVID-19). METHODS: In this randomized controlled trial, we assigned high risk COVID-19 patients with ≤10 days of symptoms, to receive cIgGs or CP. The primary endpoint was improvement on day 14 according to the World Health Organization scale. Secondary endpoints were survival on day 14, and improvement, survival, and percent of ventilated patients on day 28, and treatment response in unvaccinated and vaccinated patients. RESULTS: A total of 319 patients were included: 166 received cIgGs and 153 CP. Median age was 64 to 66 years. A total of 112 patients (67.5%) in the cIgG group and 103 patients (67.3%) in the CP group reached the primary endpoint. Difference between groups was 0.1 (95% confidence interval, -10.1 to 10.4; P = .026), failing to reach noninferiority. More patients receiving cIgG improved by day 28 (136 patients [81.9%] and 108 patients [70.6%], respectively; 95% confidence interval, 1.9-20.7; P < .001; for superiority P = .018). Seventeen patients in the cIgG group (10.2%) and 25 patients (16.3%) in the CP group required mechanical ventilation (P = .136). Sixteen (9.6%) and 23 (15%) patients, respectively, died (P = .172). More unvaccinated patients improved by day 28 in the cIgG group (84.1% vs 66.1%; P = .024), and survival was better in the cIgG group (89.9% vs 77.4%; P = .066). CONCLUSIONS: cIgGs failed to reach the primary noninferiority endpoint on day 14 but was superior to CP on day 28. Survival and improvement by day 28 in unvaccinated patients treated with cIgGs were better. In the face of new variants, cIgGs are a viable option for treating COVID-19. TRIAL REGISTRATION NUMBER: My Trials MOH_2021-01-14_009667.

Lower Serologic Response to COVID-19 mRNA Vaccine in Patients With Inflammatory Bowel Diseases Treated With Anti-TNFα.

BACKGROUND & AIM: Patients with inflammatory bowel diseases (IBD), specifically those treated with anti-tumor necrosis factor (TNF)α biologics, are at high risk for vaccine-preventable infections. Their ability to mount adequate vaccine responses is unclear. The aim of the study was to assess serologic responses to messenger RNA-Coronavirus Disease 2019 vaccine, and safety profile, in patients with IBD stratified according to therapy, compared with healthy controls (HCs). METHODS: Prospective, controlled, multicenter Israeli study. Subjects enrolled received 2 BNT162b2 (Pfizer/BioNTech) doses. Anti-spike antibody levels and functional activity, anti-TNFα levels and adverse events (AEs) were detected longitudinally. RESULTS: Overall, 258 subjects: 185 IBD (67 treated with anti-TNFα, 118 non-anti-TNFα), and 73 HCs. After the first vaccine dose, all HCs were seropositive, whereas ∼7% of patients with IBD, regardless of treatment, remained seronegative. After the second dose, all subjects were seropositive, however anti-spike levels were significantly lower in anti-TNFα treated compared with non-anti-TNFα treated patients, and HCs (both P < .001). Neutralizing and inhibitory functions were both lower in anti-TNFα treated compared with non-anti-TNFα treated patients, and HCs (P < .03; P < .0001, respectively). Anti-TNFα drug levels and vaccine responses did not affect anti-spike levels. Infection rate (∼2%) and AEs were comparable in all groups. IBD activity was unaffected by BNT162b2. CONCLUSIONS: In this prospective study in patients with IBD stratified according to treatment, all patients mounted serologic response to 2 doses of BNT162b2; however, its magnitude was significantly lower in patients treated with anti-TNFα, regardless of administration timing and drug levels. Vaccine was safe. As vaccine serologic response longevity in this group may be limited, vaccine booster dose should be considered.

The Incidence of SARS-CoV-2 Reinfection in Persons With Naturally Acquired Immunity With and Without Subsequent Receipt of a Single Dose of BNT162b2 Vaccine : A Retrospective Cohort Study.

BACKGROUND: There is insufficient evidence regarding the magnitude and durability of protection conferred by a combined effect of naturally acquired immunity after SARS-CoV-2 infection and vaccine-induced immunity. OBJECTIVE: To compare the incidence rate of SARS-CoV-2 reinfection in previously infected persons to that of previously infected persons who subsequently received a single dose of BNT162b2 messenger RNA vaccine. DESIGN: A retrospective cohort study emulating a randomized controlled target trial through a series of nested trials. SETTING: Nationally centralized database of Maccabi Healthcare Services, Israel. PARTICIPANTS: Persons with documented SARS-CoV-2 infection who did not receive subsequent SARS-CoV-2 vaccination were compared with persons with documented SARS-CoV-2 infection who received a single dose of the BNT162b2 vaccine at least 3 months after infection. INTERVENTION: Forty-one randomized controlled trials were emulated, in which 107 413 Maccabi Healthcare Services' members aged 16 years and older were eligible for at least 1 trial. MEASUREMENTS: SARS-CoV-2-related outcomes of infection, symptomatic disease, hospitalization, and death, between 2 March and 13 December 2021. RESULTS: A statistically significant decreased risk (hazard ratio, 0.18 [95% CI, 0.15 to 0.20]) for reinfection was found among persons who were previously infected and then vaccinated versus those who were previously infected but remained unvaccinated. In addition, there was a decreased risk for symptomatic disease (hazard ratio, 0.24 [CI, 0.20 to 0.29]) among previously infected and vaccinated persons compared with those who were not vaccinated after infection. No COVID-19-related mortality cases were found. LIMITATION: Hybrid protection against non-Delta variants could not be inferred. CONCLUSION: Persons previously infected with SARS-CoV-2 gained additional protection against reinfection and COVID-19 from a subsequent single dose of the BNT162b2 vaccine. Nonetheless, even without a subsequent vaccination, reinfection appeared relatively rare. PRIMARY FUNDING SOURCE: None.

Effectiveness of BNT162b2 mRNA Coronavirus Disease 2019 (COVID-19) Vaccine Against Acquisition of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Among Healthcare Workers in Long-Term Care Facilities: A Prospective Cohort Study.

BACKGROUND: We assessed vaccine effectiveness (VE) of BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) acquisition among healthcare workers (HCWs) of long-term care facilities (LTCFs). METHODS: This prospective study, in the framework of the "Senior Shield" program in Israel, included routine weekly nasopharyngeal SARS-CoV-2 RT-PCR testing from all LTCF HCWs since July 2020. All residents and 75% of HCWs were immunized between December 2020 and January 2021. The analysis was limited to HCWs adhering to routine testing. Fully vaccinated (14+ days after second dose; n = 6960) and unvaccinated (n = 2202) HCWs were simultaneously followed until SARS-CoV-2 acquisition or end of follow-up, 11 April 2021. Hazard ratios (HRs) for vaccination versus no vaccination were calculated (Cox proportional hazards regression models, adjusting for sociodemographics and residential-area COVID-19 incidence). VE was calculated as (1- HR) × 100. RT-PCR cycle threshold (Ct) values were compared between vaccinated and unvaccinated HCWs. RESULTS: At >14 days post-second dose, 40 vaccinated HCWs acquired SARS-CoV-2 (median follow-up, 66 days; cumulative incidence, 0.6%) versus 84 unvaccinated HCWs (median follow-up, 43 days; cumulative incidence, 5.1%) (HR, .11; 95% CI, .07-.17; unadjusted VE, 89%; 95% CI, 83-93%). Adjusted VE >7 and >14 days post-second dose were similar. The median PCR Ct targeting the ORF1ab gene among 20 vaccinated and 40 unvaccinated HCWs was 32.0 versus 26.7, respectively (P value  = .008). CONCLUSIONS: VE following 2 doses of BNT162b2 against SARS-CoV-2 acquisition in LTCF HCWs was high. The lower viral loads among SARS-CoV-2-positive HCWs suggest further reduction in transmission.

The Effectiveness of the Two-Dose BNT162b2 Vaccine: Analysis of Real-World Data.

BACKGROUND: Coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines were shown to be highly efficacious in preventing the disease in randomized controlled trials; nonetheless, evidence on the real-world effectiveness of this vaccine is limited. Study objective was to evaluate the effectiveness of BNT162b2 vaccine in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19-related hospitalization and mortality. METHODS: This historical cohort study included members of a large health provider in Israel that were vaccinated with at least 1 dose of BNT162b2. The primary outcome was incidence rate of a SARS-CoV-2 infection confirmed with real-time polymerase chain reaction (rt-PCR), between 7 and 27 days after second dose (protection-period), as compared to days 1-7 after the first dose, where no protection by the vaccine is assumed (reference-period). RESULTS: Data of 1 178 597 individuals vaccinated with BNT162b2 were analyzed (mean age 47.7 years [SD = 18.1], 48.4% males) of whom 872 454 (74.0%) reached the protection period. Overall, 4514 infections occurred during the reference period compared to 728 during the protection period, yielding a weighted mean daily incidence of 54.8 per 100 000 (95% confidence interval [CI]: 26.1-115.0 per 100 000) and 5.4 per 100 000 (95% CI: 3.5-8.4 per 100 000), respectively. The vaccine effectiveness in preventing infection was 90% (95% CI: 79%-95%) and 94% (95% CI: 88%-97%) against COVID-19. Among immunosuppressed patients, vaccine effectiveness against infection was 71% (95% CI: 37%-87%). The adjusted hazard ratios for hospitalization in those infected were 0.82 (95% CI: .36-1.88), 0.45 (95% CI: .23-.90), and 0.56 (95% CI: .36-.89) in the age groups 16-44, 45-64. and ≥75 years, respectively. CONCLUSIONS: The effectiveness of the BNT162b2 vaccine is comparable to the one reported in the phase III clinical trial.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Naturally Acquired Immunity versus Vaccine-induced Immunity, Reinfections versus Breakthrough Infections: A Retrospective Cohort Study.

BACKGROUND: Waning of protection against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) conferred by 2 doses of the BNT162b2 vaccine begins shortly after inoculation and becomes substantial within 4 months. With that, the impact of prior infection on incident SARS-CoV-2 reinfection is unclear. Therefore, we examined the long-term protection of naturally acquired immunity (protection conferred by previous infection) compared to vaccine-induced immunity. METHODS: A retrospective observational study of 124 500 persons, compared 2 groups: (1) SARS-CoV-2-naive individuals who received a 2-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine, and (2) previously infected individuals who have not been vaccinated. Two multivariate logistic regression models were applied, evaluating four SARS-CoV-2-related outcomes-infection, symptomatic disease (coronavirus disease 2019 [COVID-19]), hospitalization, and death-between 1 June and 14 August 2021, when the Delta variant was dominant in Israel. RESULTS: SARS-CoV-2-naive vaccinees had a 13.06-fold (95% confidence interval [CI], 8.08-21.11) increased risk for breakthrough infection with the Delta variant compared to unvaccinated-previously-infected individuals, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant for symptomatic disease as well. When allowing the infection to occur at any time between March 2020 and February 2021, evidence of waning naturally acquired immunity was demonstrated, although SARS-CoV-2 naive vaccinees still had a 5.96-fold (95% CI: 4.85-7.33) increased risk for breakthrough infection and a 7.13-fold (95% CI: 5.51-9.21) increased risk for symptomatic disease. CONCLUSIONS: Naturally acquired immunity confers stronger protection against infection and symptomatic disease caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 2-dose vaccine-indued immunity.

Helicobacter pylori and the intestinal microbiome among healthy school-age children.

BACKGROUND: Helicobacter pylori (H. pylori) infection is acquired during childhood and causes chronic gastritis that remains asymptomatic in most infected people. H. pylori alters the gastric microbiota and causes peptic ulcer disease. Evidence on the relationship between asymptomatic H. pylori infection and children's gut microbiota remains elusive. AIM: We characterized the relationship between H. pylori infection and the intestinal microbiome of healthy children, adjusting for known inter-personal and environmental exposures. MATERIALS AND METHODS: This cross-sectional study included stool samples obtained from 163 Israeli Arab children aged 6-9 years from different socioeconomic strata. Sociodemographic information was collected through maternal interviews. H. pylori infection was determined using monoclonal antigen detection stool enzyme immunoassay. The gut microbiome was characterized by implementing 16S rRNA gene sequencing of the V4 region and a multivariate downstream analysis. RESULTS: Overall, 57% of the participants were positive for H. pylori infection and it was significantly associated with low socioeconomic status. There was no significant association between H. pylori infection and bacterial richness of fecal microbiome. H. pylori infection was significantly associated with intestinal bacterial composition, including a strong association with Prevotella copri and Eubacterium biforme. Moreover, socioeconomic status was strongly associated with bacterial composition. DISCUSSION AND CONCLUSIONS: H. pylori infection in healthy children was significantly associated with altered intestinal microbiome structure. Socioeconomic determinants exhibit a strong effect, related to both H. pylori infection and intestinal diversity and composition in childhood. These findings are clinically important to the understanding of the role of H. pylori infection and other intestinal microbes in health and disease.

Role of a fluid-phase PRR in fighting an intracellular pathogen: PTX3 in Shigella infection.

Shigella spp. are pathogenic bacteria that cause bacillary dysentery in humans by invading the colonic and rectal mucosa where they induce dramatic inflammation. Here, we have analyzed the role of the soluble PRR Pentraxin 3 (PTX3), a key component of the humoral arm of innate immunity. Mice that had been intranasally infected with S. flexneri were rescued from death by treatment with recombinant PTX3. In vitro PTX3 exerts the antibacterial activity against Shigella, impairing epithelial cell invasion and contributing to the bactericidal activity of serum. PTX3 is produced upon LPS-TLR4 stimulation in accordance with the lipid A structure of Shigella. In the plasma of infected patients, the level of PTX3 amount only correlates strongly with symptom severity. These results signal PTX3 as a novel player in Shigella pathogenesis and its potential role in fighting shigellosis. Finally, we suggest that the plasma level of PTX3 in shigellosis patients could act as a biomarker for infection severity.

Helicobacter pylori infection, serum pepsinogens as markers of atrophic gastritis, and leukocyte telomere length: a population-based study.

BACKGROUND: Persistent infections that induce prolonged inflammation might negatively affect the leukocyte telomere length (LTL); however, the role in LTL of Helicobacter pylori (H. pylori) infection, which persistently colonizes the stomach, remains unknown. The study objective was to examine associations of sero-prevalence of H. pylori immunoglobulin G (IgG) antibody and serum pepsinogens (PGs), as markers of atrophic gastritis, with LTL. A cross-sectional study was performed among 934 Arab residents of East Jerusalem, aged 27-78 years, randomly selected from Israel's national population registry. Sera were tested for H. pylori IgG and PG levels by ELISA. LTL was measured by southern blots. Multiple linear regression models were fitted to adjust for sociodemographic and lifestyle factors. RESULTS: LTL decreased significantly with age (p < 0.001) and was shorter in men than women (p = 0.032). The mean LTL was longer in H. pylori sero-positive persons than negative ones: mean difference 0.13 kb (95% CI 0.02, 0.24), p = 0.016. Participants with atrophic gastritis (PGI < 30 µg/L or a PGI: PGII < 3.0) had shorter LTL than did those without: mean difference - 0.18 (95% CI - 0.32, - 0.04). The difference was of larger magnitude between persons who had past H. pylori infection (sero-negative to H. pylori IgG antibody) and atrophic gastritis, compared to those who were H. pylori sero-negative and did not have atrophic gastritis: mean difference - 0.32 kb (95% CI - 0.55, - 0.10). This association remained significant after adjustment for age, sex, and religiosity: beta coefficient - 0.21 kb (95% CI - 0.41, - 0.001), p = 0.049. The results were similar after further adjustment for lifestyle factors. In bivariate analysis, mean LTL was longer in physically active persons than non-active ones, and shorter in persons with than without obesity; however, these differences were diminished and were not significant in the multivariable model. CONCLUSIONS: H. pylori IgG sero-positivity per se was not related to reduced LTL. However, persons with past H. pylori infection (i.e., lacking H. pylori IgG serum antibody) and with serological evidence of atrophic gastritis, had a significantly shorter LTL than did those without atrophic gastritis.

Clostridium difficile-associated disease and Helicobacter pylori seroprevalence: A case-control study.

BACKGROUND: Helicobacter pylori inhabits the stomach and causes persistent inflammation, with changes in gastric acidity. However, it is unclear whether the presence of H pylori plays a role in Clostridium difficile-associated disease (CDAD). The study's aim was to examine relationships of H pylori seroprevalence and serum pepsinogens (PGs), as markers of gastric inflammation, with CDAD. MATERIALS AND METHODS: A case-control study was conducted among 49 CDAD cases and 54 controls (median age 82 years). Using enzyme-linked immunosorbent assays, sera were tested for H pylori IgG antibody, and PGI and PGII levels. Helicobacter pylori-positive samples were tested for IgG antibody to recombinant cytotoxin-associated gene A (CagA) virulent protein. Logistic regression models were fitted. RESULTS: Cases and controls were comparable in age (P = .5) and sex distribution (females 62% vs 57%, P = .6). Helicobacter pylori IgG seroprevalence was 47%, of whom 23% were CagA seropositives. Among cases compared to controls, 43% vs 28% were H pylori seropositive but lacking CagA IgG antibody: adjusted odd ratio (OR) 3.43 (95% confidence intervals [CI] 1.29-9.10); 18% vs 4% were positive for CagA phenotype: adjusted OR 9.32 (95% CI 1.61-53.76). This association was not affected by PG levels. CONCLUSIONS: Helicobacter pylori infection, especially with CagA virulent phenotype, might predispose to C difficile infection in elderly patients.

Consensus Report on Shigella Controlled Human Infection Model: Immunological Assays.

Moderate to severe diarrhea caused by Shigella is a global health concern due to its substantial contribution to morbidity and mortality in children aged <5 years in low- and middle-income countries. Although antibiotic treatment can be effective, emerging antimicrobial resistance, limited access, and cost affirm the role of vaccines as the most attractive countermeasure. Controlled human infection models (CHIMs) represent a valuable tool for assessing vaccine efficacy and potentially accelerating licensure. Currently, immunological analysis during CHIM studies is customized based on vaccine type, regimen, and administration route. Additionally, differences in type of immunoassays and procedures used limit comparisons across studies. In November 2017, an expert working group reviewed Shigella CHIM studies performed to date and developed consensus guidelines on prioritization of immunoassays, specimens, and collection time points. Immunoassays were ranked into 3 tiers, with antibodies to Shigella lipopolysaccharide (LPS) being the highest priority. To facilitate comparisons across clinical studies, a second workshop was conducted in December 2017, which focused on the pathway toward a recognized enzyme-linked immunosorbent assay (ELISA) to determine serum immunoglobulin G titers against Shigella LPS. The consensus of the meeting was to establish a consortium of international institutions with expertise in Shigella immunology that would work with the National Institute for Biological Standards and Control to establish a harmonized ELISA, produce a reference sera, and identify a reliable source of Shigella LPS for global utilization. Herein we describe efforts toward establishing common procedures to advance Shigella vaccine development, support licensure, and ultimately facilitate vaccine deployment and uptake.

Risk factors for recurrent Clostridium difficile infection in a tertiary hospital in Israel.

To estimate the rate and identified risk factors for recurrent Clostridium difficile infection (rCDI) in Israel. We conducted a retro-prospective case-control study of all adult (age ≥ 18 years) patients with an initial episode of CDI (iCDI) at Tel Aviv Sourasky Medical Center from January 1, 2012 to December 31, 2014. We collected demographic, clinical, and epidemiological information for patients who were classified as recurrent (cases) and non-recurrent (control) groups. In total, 648 patients with iCDI were identified in the study. During the 36-month study period, 82 (12.7%) patients had at least one rCDI identified. We identified several factors as independent variables significantly associated with recurrent CDI: functional disability, severity of the initial infection, continuous non-Clostridium difficile antibiotic treatment with third-generation cephalosporins or clindamycin, and iCDI treatment with metronidazole and vancomycin; however, neutropenia had high measure of effect as a predictor for rCDI (adjusted odds ratio, 7.9; 95% confidence interval, 1.27-49.58; p = 0.026). The identification of the main modifiable risk factors for recurrent CDI, continuous non-Clostridium difficile antibiotics after diagnosis of the initial infection, and antibiotic treatment with third-generation cephalosporins or clindamycin are critical in reducing the spread of recurrent infection with Clostridium difficile in hospital.

Travel- and Community-Based Transmission of Multidrug-Resistant Shigella sonnei Lineage among International Orthodox Jewish Communities.

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.

Prevalence of hepatitis E virus antibodies, Israel, 2009-2010.

We investigated prevalence of hepatitis E virus in a sample of the population of Israel. The overall seroprevalence of antibodies to the virus was 10.6% (95% CI 8.4%-13.0%); age-adjusted prevalence was 7.6%. Seropositivity was associated with age, Arab ethnicity, low socioeconomic status, and birth in Africa, Asia, or the former Soviet Union.

Helicobacter pylori Infection in Early Childhood and Growth at School Age.

BACKGROUND: There are conflicting results regarding the role of H. pylori in children's growth. We examined differences in growth indices at school age according to H. pylori infection acquisition in preschool age. MATERIALS AND METHODS: A prospective study was undertaken between 2004 and 2009, in which of healthy children (N = 139, ages 3-5 years at baseline) were tested for the presence of H. pylori antigen in their stool using enzyme-linked immunoassay and followed-up till age 6-9 years (median follow-up time 45 months). Height, weight, and hemoglobin levels were measured, and socioeconomic data were obtained. Z scores of height for age, weight for age, and body mass index for age at baseline and follow-up were calculated using the 2000 Center for Disease Control and Prevention growth reference curves. Growth velocity (cm/month) between preschool and school age was compared between H. pylori-infected and uninfected children using mixed models. RESULTS: Fifty-three percent of the children were H. pylori positive at baseline, and all except one child tested positive at follow-up. The adjusted mean Z score of height for age at follow-up was significantly lower among H. pylori-infected children than uninfected ones: 0.15 (95% confidence intervals (CIs) 0.02, 0.29) and 0.45 (95% CI 0.29, 0.60), respectively (p = .002). Growth velocity was slower in the former group -0.0264 cm/month (95% CI -0.047, -0.005) (p = .014), after adjusting for baseline height and age. H. pylori infection was not associated with body weight. CONCLUSIONS: Helicobacter pylori infection acquired in early childhood may have long-term adverse influence on linear growth at school age.

Involvement of main diarrheagenic Escherichia coli, with emphasis on enteroaggregative E. coli, in severe non-epidemic pediatric diarrhea in a high-income country.

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.

Change in incidence of clinic visits for all-cause and rotavirus gastroenteritis in young children following the introduction of universal rotavirus vaccination in Israel.

Both rotavirus vaccines RotaTeq and Rotarix were efficacious against severe rotavirus gastroenteritis in clinical trials; yet real-world data on the effect of rotavirus vaccines on mild to moderate disease are limited. We used a large computerised database of Maccabi Health Services Health Maintenance Organisation (HMO), the second largest HMO in Israel covering 25% of the Israeli population, to compare the incidence of acute gastroenteritis (AGE) clinic visits in community settings (n=302,445) before (2005-10) and after (2011-13) the introduction of universal rotavirus immunisation in Israel. We retrieved laboratory results of rotavirus antigen tests (n=18,133) and using a weighted analysis, we estimated the impact of rotavirus immunisation on the disease burden of rotavirus AGE clinic visits. Following the introduction of universal rotavirus immunisation, the typical winter peaks of rotavirus AGE were substantially lower and significant reductions of 14.8% (95% confidence interval (CI): 13.5-16.1) in all-cause AGE clinic visits and of 59.7% (95% CI: 59.8-62.6) in rotavirus AGE clinic visits were observed. The decrease was observed in all age groups, but it was greater in children aged 0 to 23 months than those aged 24 to 59 months. Continued rotavirus laboratory surveillance is warranted to monitor the sustainability of these changes.

Recent trends of cervical cancer and Cervical Intraepithelial Neoplasia 3 (CIN3) in Israel.

PURPOSE: This study describes time trends of cervical cancer and Cervical Intraepithelial Neoplasia 3 (CIN3) in Israel in the years 1986-2010 and characterizes these patients by demographics. METHODS: A retrospective survey based on cervical cancer and CIN3 data documented in the computerized system of the second largest Health Maintenance Organizations (HMO) in Israel, "Maccabi Healthcare Services" (MHS) between 1986 and 2010. RESULTS: 737 cervical cancer patients and 3,459 patients of CIN3 were reported between 1986 and 2010. The mean age of women with cervical cancer was significantly higher (mean 49.1 years) than that of CIN3 patients (mean 36.3 years) (p-value < 0.0001). The annual age-adjusted incidence rate of cervical cancer increased significantly from 1.6 per 100,000 in 1986 to 3.7 per 100,000 in 2010 (p for trend = 0.0001) and for CIN3, from 3.9 per 100,000 in 1986 to 40.4 per 100,000 in 2010 (p for trend = 0.0001). For cervical cancer, using the Joinpoint software we demonstrated an increase in the age-adjusted incidence rate between 1986 and 2003 and since then, a decrease was observed. Cervical cancer and CIN3 were mostly common in the Tel Aviv District. CONCLUSIONS: Although quite low to begin with, the incidence rates of cervical cancer and CIN3 in Israel may be further lowered by implementing an organized screening program and introduction of the HPV vaccine into the national immunization program.