Real-time genomic investigation underlying the public health response to a Shiga toxin-producing Escherichia coli O26:H11 outbreak in a nursery.

Shiga toxin-producing Escherichia coli (STEC) is a significant cause of gastrointestinal infection and the haemolytic-uremic syndrome (HUS). STEC outbreaks are commonly associated with food but animal contact is increasingly being implicated in its transmission. We report an outbreak of STEC affecting young infants at a nursery in a rural community (three HUS cases, one definite case, one probable case, three possible cases and five carriers, based on the combination of clinical, epidemiological and laboratory data) identified using culture-based and molecular techniques. The investigation identified repeated animal contact (animal farming and petting) as a likely source of STEC introduction followed by horizontal transmission. Whole genome sequencing (WGS) was used for real-time investigation of the incident and revealed a unique strain of STEC O26:H11 carrying stx2a and intimin. Following a public health intervention, no additional cases have occurred. This is the first STEC outbreak reported from Israel. WGS proved as a useful tool for rapid laboratory characterization and typing of the outbreak strain and informed the public health response at an early stage of this unusual outbreak.

Public health response to the silent reintroduction of wild poliovirus to Israel, 2013-2014.

During 2013/14, Israel witnessed the silent reintroduction and sustained transmission of wild poliovirus type 1 (WPV1) detected through routine environmental surveillance performed on sewage samples. The public health response to silent poliovirus transmission in a population with high inactivated polio vaccine (IPV) coverage poses an emerging challenge towards the 'End Game' of global poliovirus eradication. This paper reviews the risk assessment, risk management and risk communication aspects of this poliovirus incident. Special emphasis is placed on the use of scientific data generated in the risk assessment phase to inform the public health response. Reintroducing a live vaccine in supplemental immunization activities in response to transmission of WPV or vaccine-derived poliovirus should be considered close to the 'End Game' of polio eradication, especially if targeting the population at risk is feasible. Such circumstances require a comprehensive contingency plan that will support the generation of important public health evidence at the risk assessment stage, thereby allowing to tailor the risk management approaches and underpin appropriate risk communication.

Socioeconomic status and vaccine coverage during wild-type poliovirus emergence in Israel.

In August 2013, a nationwide vaccination campaign with bivalent oral polio vaccine (bOPV) was initiated after isolation of wild-type poliovirus type 1 (WPV-1) in routine sewage surveillance in Israel. The campaign started in the Southern district and later extended to the entire country. This study examined the association between socioeconomic status (SES), and compliance with bOPV vaccine during the campaign. Nationwide data relating to SES by geographical cluster were correlated with vaccine coverage rates in the same areas. All analyses were conducted separately for Jews and Arabs. Coverage with the bOPV vaccination campaign in the Arab population (92·4%) was higher than in the Jewish population (59·2%). This difference was consistently present in all SES clusters. In the Jewish population there was an inverse correlation between SES and vaccination coverage rates (R = -0·93, P < 0·001). Lower vaccination coverage with supplemental vaccine activities in higher SES groups is a challenge that needs to be addressed in future public health events and emergencies in order to achieve satisfactory protection rates for the public.

Silent reintroduction of wild-type poliovirus to Israel, 2013 - risk communication challenges in an argumentative atmosphere.

Israel has been certified as polio-free by the World Health Organization and its routine immunisation schedule consists of inactivated poliovirus vaccine (IPV) only. At the end of May 2013, the Israeli Ministry of Health (MOH) has confirmed the reintroduction of wild-type poliovirus 1 into the country. Documented ongoing human-to-human transmission necessitated a thorough risk assessment followed by a supplemental immunisation campaign using oral polio vaccine (OPV). The unusual situation in which ongoing poliovirus transmission was picked up through an early warning system of sewage monitoring without active polio cases, brought about significant challenges in risk communication. This paper reviews the challenges faced by the MOH and the communication strategy devised, in order to facilitate and optimise the various components of the public health response, particularly vaccination. Lessons learned from our recent experience may inform risk communication approaches in other countries that may face a similar situation as global polio eradication moves towards the 'End game'.

Insidious reintroduction of wild poliovirus into Israel, 2013.

Israel was certified as polio-free country in June 2002, along with the rest of the World Health Organization European Region. Some 11 years later, wild-type polio virus 1 (WPV1) was isolated initially from routine sewage samples collected between 7 and 13 April 2013 in two cities in the Southern district. WPV1-specific analysis of samples indicated WPV1 introduction into that area in early February 2013. National supplementary immunisation with oral polio vaccine has been ongoing since August 2013.

Can parametrectomy be avoided in early cervical cancer? An algorithm for the identification of patients at low risk for parametrial involvement.

AIMS: To assess the rate of parametrial involvement in a large cohort of patients who underwent radical hysterectomy for cervical cancer and to suggest an algorithm for the triage of patients to simple hysterectomy or simple trachelectomy. METHODS: Multicenter retrospective study of patients with cervical cancer stage I through IIA who underwent radical hysterectomy and pelvic lymphadenectomy. The patients were divided into 2 groups according to whether or not the parametrium was involved. The two groups were compared with regard to the clinical and histopathological variables. Logistic regression of the variables potentially assessable prior to definitive hysterectomy such as age, tumor size, lymph-vascular space invasion (LVSI) and nodal involvement was performed. RESULTS: Five hundred and thirty patients had specific histological data on parametrial involvement and in 58 (10.9%) patients, parametria was involved. Parametrial involvement was significantly associated with older age, tumors larger than 2 cm, deeper invasion, LVSI, involved surgical margins, and the presence of nodal metastasis. By triaging patients with a tumor ≤ 2 cm and no LVSI, the parametrial involvement rate was 1.8% (2/112 patients). With further triage of patients with negative nodes, the rate of parametrial involvement was 0% (0/107 patients). CONCLUSION: Using a pre-operative triage algorithm, patients with early small lesions, no LVSI and no nodal involvement may be spared radical surgical procedures and parametrectomy. Further prospective data are urgently needed.

Temporal pattern of recurrence of stage I endometrial cancer in relation to histological risk factors.

OBJECTIVE: To study the temporal pattern of endometrial cancer recurrence in relation to histological risk factors in a large multicenter setting. METHODS: 843 patients with apparent stage I endometrial cancer were followed for a median time of 38 months, documenting all recurrences. Patients were stratified as high risk based on the presence of at least one of the established histological risk factors: high tumor grade, penetration to the outer half of the myometrium, lymphvascular space involvement, lower uterine segment involvement and non endometroid histology. Survival analysis, including Kaplan-Meier curves, log-rank tests and multi-variate Cox proportional hazard regression were used to evaluate the equality of recurrence-free distributions for different levels of risk. RESULTS: Recurrence was documented in 66 cases. The presence of one or more of the histological risk factors was associated with significantly shorter recurrence free survival, not attenuating over time (p < 0.001). Age-adjusted Cox regression model demonstrated a significantly decreased recurrence-free survival (HR = 2.8 95% CI 1.5, 5.1) in the presence of risk factors. CONCLUSIONS: In patients with stage I endometrial cancer, the presence of histological risk factors is associated with a significantly higher recurrence rate, which does not attenuate over follow up time. This may allow for a selective approach in the follow- up of endometrial cancer patients.

Pemphigus, analysis of 155 patients.

BACKGROUND: Pemphigus vulgaris is a chronic autoimmune mucocutaneous blistering disease. In the last 20 years, immunomodulatory agents have been added to the therapeutic armamentarium. Only few recent studies have evaluated the long-term outcome of pemphigus and possible prognostic parameters in a large group of patients. The aim of this study was to evaluate and analyse the course and prognostic factors of pemphigus in patients followed from 1976 to 2004. PATIENTS AND METHODS: The study group consisted of 155 patients attending the pemphigus clinic of a major tertiary-care medical centre. Background, clinical and treatment data were derived from the patient files and telephone contact. Statistical analysis was performed with Pearson correlation, Fisher exact test, and univariate and multivariate logistic regression models. RESULTS: Age < 40 years at disease onset, Sephardic Jewish origin, and mucosal involvement at diagnosis and high number of relapses were found to be independent prognostic factors of poor outcome. A long (> 1 year) primary remission was a good prognostic factor. During the 26-year study period, 16 patients died. None of the deaths was directly related to either the disease or a complication of treatment. CONCLUSIONS: The course and outcome of pemphigus are worse in patients who are young at diagnosis (< 40 years) or of Sephardic Jewish origin. Mucosal involvement at diagnosis and poor response to treatment also predict poor outcome. The mortality rate of pemphigus is apparently lower than reported in the literature, perhaps because of the contemporary use of adjuvant immunomodulatory therapeutic agents.

A multicenter validation of computerized tomography models as predictors of non- optimal primary cytoreduction of advanced epithelial ovarian cancer.

AIMS: To compare the validity of four predictive models of preoperative computerized tomography (CT) scans in predicting suboptimal primary cytoreduction in patients treated for advanced ovarian cancer. PATIENTS AND METHODS: Preoperative CT scans of patients with stage III/IV epithelial ovarian cancer who underwent primary cytoreductive surgery at one of four medical centers were reviewed by radiologists blinded to surgical outcome. The validity of each set of CT criteria previously published by Nelson, Bristow, Dowdy, and Qayyum as predictors of suboptimal cytoreduction was assessed. RESULTS: Data of 123 patients were evaluated. Optimal cytoreduction (largest diameter of residual tumor < or =1cm) was obtained in 90 (73.2%) patients. All CT models were able to significantly predict surgical outcome (p<0.02). The respective sensitivity, specificity, and accuracy of the CT models to predict sub-optimal cytoreduction was 64%, 64% and 64% for Nelson's criteria, 70%, 64% and 66% for Bristow's criteria, 79%, 60%, and 65% for Dowdy's criteria, and 67% 57% and 60% for Qayyum's criteria. CONCLUSIONS: Apart from Dowdy's criteria, the accuracy rates of CT predictors of suboptimal cytoreduction in the original cohorts could not be confirmed in this cross validation. This study underscores the difficulty in devising universally applicable selection criteria or models that reliably predict surgical outcome across institutions and surgeons.

The reproducibility of histological parameters employed in the novel binary grading systems of endometrial cancer.

OBJECTIVE: To compare the interobserver reproducibility and prognostic value of the FIGO grading system with the histological parameters employed in the various recently proposed binary grading systems of endometrial cancer. METHODS: Seventy two consecutive stage I endometrioid endometrial carcinomas from hysterectomy specimens were independently graded by two pathologists. Clinical data and outcome were obtained from the patients' records. The following histological parameters were evaluated: FIGO grade (dichotomized to grades 1 and 2 vs. grade 3), nuclear atypia, presence of more than 50% solid growth, diffusely infiltrative rather than expansive growth pattern, presence of tumor cell necrosis, and mitotic count. Interobserver agreement was measured by the kappa (k) statistics. Kaplan-Meier survival analysis, log-rank tests and Cox proportional hazard regression were used to evaluate the equality of survival distributions and to model the overall effects of the various predictor variables on survival. RESULTS: The interobserver reproducibility was as follows: FIGO grade, k=0.65; nuclear atypia, k=0.63; solid growth, k=0.51; infiltrative growth pattern, k=0.38; tumor necrosis, k=0.52; and mitotic index, k=0.44. In the comparison of the Kaplan-Meier curves, the following parameters were associated with a significantly poorer survival: FIGO grade 3, p=0.02; presence of more than 50% solid growth, p=0.01; and a high mitotic index, p=0.01. The other binary histological parameters were not significantly predictive of survival. CONCLUSIONS: The proposed novel binary grading parameters are not advantageous in terms of interobserver reproducibility and prognostic significance over dichotomization to FIGO grades 1 and 2 vs. grade 3. A simple binary grade based solely on presence of more than 50% solid growth has a comparable reproducibility and prognostic value.

Lower uterine segment involvement is associated with adverse outcome in patients with stage I endometroid endometrial cancer: results of a multicenter study.

OBJECTIVE: To quantify the relative risk associated with lower uterine segment involvement (LUSI) on outcome measures in patients with apparent stage I endometroid endometrial cancer. METHODS: A cohort of 769 consecutive patients with endometroid endometrial carcinoma apparent stage I, who underwent surgery in five gynecological oncology centers in Israel; 138 patients with and 631 without LUSI were followed for a median time of 51 months. Local recurrence, recurrence-free and overall survival were compared between the two groups. RESULTS: LUSI was associated with grade 3 tumor (p=0.002), deep myometrial invasion (p<0.001), and the presence of lymphvascular space involvement (p=0.01). There were 22 cases of local recurrences, 40 cases of distal recurrences and 80 patients died. Univariate survival analysis showed that patients with LUSI had trend toward lower regional recurrence-free survival (p=0.09), and significant lower distant recurrence-free survival (p=0.04) and lower overall survival (p=0.002). The Cox proportional hazards model demonstrated a significantly decreased overall survival (HR=2.3; 95% CI 1.3, 3.9; p=0.003) in cases with LUSI. CONCLUSIONS: In patients with apparent stage I endometroid endometrial cancer, the presence of LUSI is a poor prognostic factor, associated with a significantly higher risk of distal recurrence and death. The presence of LUSI warrants consideration when deciding upon surgical staging or postoperative management.

Pemphigus--analysis of epidemiological factors in 155 patients.

BACKGROUND: Pemphigus vulgaris is a chronic autoimmune mucocutaneous blistering disease. Only a few studies have evaluated the epidemiological and aetiological parameters of pemphigus vulgaris in a large group of patients over the long term. METHODS: The sample included 155 patients with a diagnosis of pemphigus who attended the pemphigus clinic of a major tertiary medical centre from 1976 to 2004. Data were obtained from the patient files and entered into an ad hoc form; patients were contacted by telephone for missing information. RESULTS: The female-to-male ratio was 1.5 : 1. Non-Ashkenazi Jews accounted for 37% of the sample. In only 10% of the patients was a potential aetiologic or precipitating factor identified. CONCLUSIONS: Pemphigus vulgaris is characterized by a female predominance, consistent with other autoimmune disease. The gender, age and ethnic distribution of affected patients have not changed in the last 40 years. In the vast majority of cases, the aetiologic or precipitating factor is unknown, although drugs appear to be very rare.

The outcome of patients with stage I endometrial cancer involving the lower uterine segment.

The objective of this study was to evaluate whether lower uterine segment involvement (LUSI) correlates with recurrence and survival in women with stage I endometrial adenocarcinoma and whether it is associated with poor prognostic histopathologic features. Three hundred seventy-five consecutive patients with endometrial carcinoma stage I compromised the study population. The patients were divided into two groups according to the presence of LUSI with endometrial carcinoma. The two groups were compared with regard to prognostic factors and outcome measures by using the Pearson chi(2) test, log-rank test, and Cox proportional hazards model. LUSI was present in 89 (24%) patients with stage I endometrial carcinoma. LUSI was significantly associated with grade 3 tumor (P = 0.022), deep myometrial invasion (P < 0.0001), and the presence of capillary space-like involvement (CSLI) (P = 0.003). Kaplan-Meier survival curves demonstrated that patients with LUSI had a lower recurrence-free survival (log-rank test; P = 0.009) and a worse overall survival (log-rank test; P = 0.0008). In the Cox proportional hazards model, only a trend toward higher recurrence rate (HR = 2.4, 95% CI 0.7, 8.2; P = 0.16) and a trend toward poorer overall survival (HR = 1.54, 95% CI 0.82, 2.91; P = 0.18) were noted when LUSI was present. In patients with stage I endometrial cancer, the presence of LUSI is associated with grade 3 tumor, deep myometrial invasion, and the presence of CSLI. A larger group of patients is necessary to conclude whether higher recurrence rate and poorer overall survival are associated with the presence of LUSI.

Mass antibiotic treatment to stop an outbreak of meningococcal disease: a molecular analysis.

The occurrence of three cases of meningococcal disease among children in a small community, two of whom attended the same day-care centre, prompted a programme of mass antibiotic prophylaxis. Nasopharyngeal and throat swabs were obtained on three occasions from all children registered at the day-care centre. Serogroup B Neisseria meningitidis was isolated from 13 of 61 children before prophylaxis, from three children after 2 weeks, and from 19 children after 3 months. Repetitive extragenic palindromic PCR analysis identified several meningococcal strains before treatment, one of which became predominant after 3 months. Mass antibiotic prophylaxis initially suppressed meningococcal carriage, but the carriage rate subsequently rebounded.

Lymphvascular space involvement compromises the survival of patients with stage I endometrial cancer: results of a multicenter study.

AIMS: To quantify the relative risk associated with lymphvascular space involvement (LVSI) on outcome measures in patients with apparent stage I endometrial cancer. METHODS: Six hundred and ninety nine consecutive patients with endometrial carcinoma apparent stage I, who underwent surgery in one of four gynecological oncology centers in Israel, comprised the study population. Forty cases with and 659 without LVSI were followed for a median time of 39 months. Recurrence free, disease specific and overall survival was compared between the two groups. The effect of LVSI, adjusted for other clinical and histo-pathological prognostic factors, was assessed by multivariate analysis. RESULTS: The univariate Kaplan-Meier procedure for survival analysis showed that patients with LVSI had lower recurrence free survival (p=0.0003), worse disease specific (p=0.0007) and overall survival (p<0.0001). Cox proportional hazards model demonstrated a trend toward shorter recurrence free survival (HR=2.0, 95% CI 0.9, 4.5; p=0.08), a worse disease specific survival (HR=2.8, 95% CI 1.1, 7.4; p=0.04) and decreased overall survival (HR=2.0, 95% CI 1.1, 3.8; p=0.03) in cases with LVSI. CONCLUSIONS: In patients with apparent stage I endometrial cancer the presence of LVSI, an independent poor prognostic factor, is associated with a two fold increased risk of death. The presence of LVSI warrants consideration when deciding upon post operative management.

A multicenter study of CA 125 level as a predictor of non-optimal primary cytoreduction of advanced epithelial ovarian cancer.

AIMS: To provide a large database of pre-operative CA 125 levels which may predict inappropriate cytoreductive surgery in patients with advanced epithelial ovarian cancer. METHODS: A multicenter review of the records of 424 patients with FIGO stage III and IV epithelial ovarian cancer of patients who underwent primary cytoreductive surgery was performed. The validity of pre-operative CA 125 level measurement as a single predictor of the possibility to achieve only suboptimal cytoreduction was evaluated by calculating the sensitivity and the specificity of various cut-off values. The relative importance of different cut-off values in achieving the best predictive validity was assessed by a receiver operating characteristics (ROC) curve. RESULTS: Optimal cytoreduction (largest diameter of residual tumour < or =1 cm) was achieved in 242 patients. The median CA 125 level in optimally cytoreduced patients was lower than in those patients suboptimally debulked (304 vs 863 U/mL; p<0.001). The area under the ROC curve was 0.65 (95% confidence interval, 0.60-0.71) and the CA 125 threshold derived from the ROC was 400 U/mL. The accuracy of the test at this level was 62%. CONCLUSIONS: The clinical applicability of the ROC derived CA 125 threshold is limited. The data accrued in the study provides a basis for decision-making regarding the place of primary surgery various CA 125 levels.

An outbreak of norovirus gastroenteritis on an Israeli military base.

BACKGROUND: Noroviruses (NVs) are a predominant cause of viral gastroenteritis outbreaks, but they are difficult to identify because they cannot be cultivated in cell culture. Therefore, reverse-transcriptase polymerase chain reaction (RT-PCR) assays are widely used in the testing of clinical stool specimens for NV. However, testing of perianal swabs in the context of an outbreak is considered to be an insensitive method for identification of NV using the RT-PCR technique. An outbreak of acute gastroenteritis involving 159 soldiers on a training base of the Israel Defense Force in December 1999 allowed us to evaluate this identification method. PATIENTS AND METHODS: An epidemiologic investigation, a sanitation survey and a case-control study of exposure to different food items served up to 48 h preceding the outbreak were conducted. Stool samples in the form of post-defecation perianal swabs were collected from 24 ill personnel and three non-ill food handlers. Swabs were tested for the presence of NV by RT-PCR assay. RESULTS: Epidemiologic data were consistent with a pointsource food-borne outbreak which was associated with consumption of fresh vegetable salad in the base mess hall (OR = 4.38, 95% CI 1.51-13.35). Both epidemiologic and clinical features were suggestive of gastroenteritis caused by NV, and upon laboratory analysis perianal swabs from four of 24 cases were positive for NV. CONCLUSION: The combination of practical specimen collection with perianal post-defecation swabs, and the utilization of a molecular epidemiology approach, can simplify the rapid identification of outbreaks caused by NVs.

Seasonality trends of scabies in a young adult population: a 20-year follow-up.

BACKGROUND: Scabies is not a notifiable disease in most countries. Therefore, its seasonality trends are usually estimated and may be inaccurate. OBJECTIVES: To determine the seasonality of scabies over the long term in a large military population, including all of the Israel Defence Forces personnel. METHODS: For the last two decades, the Israel Defence Forces have mandated the routine reportage of every case of scabies infestation in soldiers to the Epidemiology Department of the Army Health Branch. This database was used in the present study to analyse the incidence of scabies by season. Scabies was defined according to the report by a military physician based on the typical clinical presentation, relevant epidemiological data and, in most cases, microscopic visualization of the mite. RESULTS: The person-time incidence of scabies was higher in winter than summer (P < 0.001). The overall risk ratio was 1.31 (95% confidence interval 1.28-1.33). Sensitivity analysis indicated that no single year was an important source of disease heterogeneity. CONCLUSIONS: Scabies in a young adult population is more frequent in the cooler months of the year.

Seasonality trends of Pediculosis capitis and Phthirus pubis in a young adult population: follow-up of 20 years.

BACKGROUND: It is not mandatory to report Pediculosis capitis and Phthirus pubis in most countries; therefore, little is known about the seasonality of these infestations. METHODS: We analysed the data based on routine and mandatory reporting of every case of Pediculosis capitis and Phthirus pubis to the Army Health Branch Epidemiology Department, Israel, over the last two decades. RESULTS: The average 20-year incidence of Pediculosis capitis shows a significant rise during the warmer months (R2 = 0.692, P < 0.05) with a parallel significant decrease in the cooler months (R2 = 0.893, P < 0.05). The results for Phthirus pubis show a significantly higher person-time incidence in the winter (P < 0.001). Sensitivity analysis to investigate possible sources of heterogeneity during this time indicated that no single year was an important source of heterogeneity. CONCLUSIONS: Pediculosis capitis is more frequent in the warmer months, whereas Phthirus pubis is more dominant in the cooler months.

Does breastfeeding protect against allergic rhinitis during childhood? A meta-analysis of prospective studies.

UNLABELLED: The effect of breastfeeding on the development of allergic rhinitis and other atopic conditions has been assessed in many studies but remains controversial. To elucidate this issue, a systematic review was conducted of prospective studies that evaluated the association between exclusive breastfeeding during the first 3 mo after birth and allergic rhinitis. The 1966-2000 MEDLINE databases were searched and the reference lists of relevant articles were reviewed according to predetermined inclusion criteria. The methodological aspects of each study, duration and exclusivity of breastfeeding, outcome measures, control for potential confounding variables and other factors were assessed, and estimates of the association between breastfeeding and allergic rhinitis were abstracted independently by the investigators using a standardized approach. Six prospective studies met the inclusion criteria. The summary odds ratio for the protective effect of breastfeeding was 0.74 (95% confidence interval 0.54-1.01). The effect estimate in studies of children with a family history of atopy was 0.87 (95% confidence interval 0.48-1.58). CONCLUSION: Exclusive breastfeeding during the first 3 mo after birth protects against allergic rhinitis in children, both with and without a family history of atopy. The protective association, although of borderline statistical significance, was substantial. Larger prospective studies with strict methodology and longer periods of follow-up are needed.