Surveillance of invasive meningococcal disease in the Tel Aviv District, Israel, 2007-2017.

Invasive meningococcal disease (IMD) is one of the leading causes of bacterial meningitis and septicemia in Israel. The purpose of the study was to describe the IMD in the Tel Aviv District and to identify specific populations who could benefit from vaccine introduction. In the Tel Aviv District, the incidence rates ranged from 0.4 to 1.4 cases per 100,000 population per year during 2007-2017. During the study period, seventy-nine patients (65%) occurred among children younger than four years of age. Eight deaths occurred (7%), most of them among children under the age of 1 year (5 deaths; 15%). A serogroup was identified in 82 isolates. Most of the isolates (69 cases - 84%) belonged to serogroup B (NmB). IMD clustered geographically in the city of Bnei Brak, with a predominantly Ultra-Orthodox Jewish population. It is the youngest and most densely populated city in the district. The overall incidence rates of IMD among children in Bnei Brak were more than seven times higher in children up to nine years, compared to the rest of the district. Specifically for NmB, disease rates were 9.08 times higher in children up to the age of four, and 7.74 times higher in children from five to nine years old in Bnei Brak, compared to the rest of the district. Our findings describe the burden of a vaccine-preventable disease and reinforce the need for routine 4CmenB introduction, especially in groups where the disease clusters.

Vaccination uptake and income inequalities within a mass vaccination campaign.

BACKGROUND: In July 2013, Israel was swept with fear of a polio outbreak. In response to the importation of wild polio virus, the Ministry decided to take preventive action by administering oral poliovirus vaccine (OPV) to all children born after 1 January 2004 who had received at least one dose of inactivated poliovirus vaccine (IPV) in the past. This study analyzes the vaccination uptake rates resulting from the mass polio vaccination campaign on the basis of health inequality parameters of socioeconomic status (SES), principles of solidarity, and the Gini inequality index. The research explores understanding the value of the Gini inequality index within the context of SES and solidarity. METHODS: The study is based on data gathered from the Israeli Ministry of Health's administrative records from mother-and-child clinics across Israel. The research population is comprised of resident infants and children whom the Ministry of Health defined as eligible for the OPV between August and December 2013 (the "campaign period"). The analysis was carried out at the municipality level as well as the statistical area level. RESULTS: The higher the SES level of the municipality where the mother-and-child clinic is located, the lower the OPV vaccination uptake is. The greater the income inequality is in the municipality where the mother-and-child clinic is situated, the lower the vaccination uptake. CONCLUSIONS: Public health professionals promoting vaccine programs need to make specially-designed efforts both in localities with high average income and in localities with a high level of income diversity/inequality. Such practice will better utilize funds, resources, and manpower dedicated to increasing vaccination uptake across varying populations and communities.

Early Referral to Coronary Artery Bypass Grafting Following Acute Coronary Syndrome, Trends and Outcomes from the Acute Coronary Syndrome Israeli Survey (ACSIS) 2000-2010.

BACKGROUND: Limited information exists on whether changes in medical practices over the study decades have affected the outcomes of acute coronary syndrome (ACS) patients who undergo early coronary artery bypass surgery (CABG) during index hospitalisation. METHODS: Data on trends for early CABG referral and associated outcomes were obtained among 11,485 ACS patients enrolled in the biennial Acute Coronary Syndrome Israeli Surveys (ACSIS) 2000-2010. RESULTS: Among 11,485 patients, 566 (5%) were referred to early CABG. These patients displayed higher risk characteristics, including Killip class >II, anterior myocardial infarction, greater left ventricular dysfunction, and more frequent use of mechanical ventilation and intra-aortic balloon pump (all p<0.01). Nevertheless, mortality rates of patients referred to early CABG vs. treated with percutaneous coronary intervention (PCI) or medically, was similar (11.4% vs. 10.2%; log-rank p-value=0.40). There was a significant decline in the referral trend over the study decade (6.7% - 1.7%; p<0.001). One year survival was similar between patients referred to early CABG during the late (years: 2006-2010) vs. early (years: 2000-2005) period (85.7% vs. 90%; log-rank p-value=0.15), whereas, among patients who didn't undergo early CABG, and underwent percutaneous coronary intervention (PCI) or medical management only, enrolment during the late periods was associated with a significant survival benefit (91.5% vs. 88.1%; log-rank p-value<0.001). CONCLUSIONS: Over the study decade there was a significant decline in referral for early CABG, without a difference in the one-year mortality between the early and non-early CABG group.

Triggers and Timing of Acute Coronary Syndromes.

Previous studies have shown that an acute coronary syndrome (ACS) may be triggered by external activities; however, their frequency, predictors, and significance are uncertain. We evaluated data from the National Israel Survey of Acute Coronary Syndromes, which was conducted in 2004 (February to March) in all 25 coronary care units and cardiac wards in Israel. Demographic and clinical data were recorded for consecutive participants, including potential triggers and time of symptom onset of ACS. Among the 1,849 patients who completed the trigger question, 1/4 (25.9%) reported a possible trigger, comprising heavy physical exertion (15.2%), emotional stress (8.3%), anger (1.1%), heavy meal (1.3%), and sexual activity (0.5%). Predictors of a triggered ACS were age <65 years, previous angina, no previous angiotensin-converting enzyme inhibitors/angiotensin 2 receptor blockers, impaired functional class, not having typical chest pain on admission, and a final diagnosis of unstable angina. The highest proportion of triggered ACS was between noon and 6 p.m. Physical exertion as a trigger was associated with reduced in-hospital mortality (0.4% vs 2.8%, p <0.05) and 1-year mortality. Emotional stress as a trigger did not influence in-hospital or 1-year mortality; however among those discharged from hospital, it was associated with increased 30-day rehospitalization (27.6% vs 19.3%, p <0.05) and a trend toward increased mortality (4.1% vs 2.0%, p = 0.10).

Cardiac rehabilitation following an acute coronary syndrome: Trends in referral, predictors and mortality outcome in a multicenter national registry between years 2006-2013: Report from the Working Group on Cardiac Rehabilitation, the Israeli Heart Society.

Background Utilization of cardiac rehabilitation is suboptimal. The aim of the study was to assess referral trends over the past decade, to identify predictors for referral to a cardiac rehabilitation program, and to evaluate the association with one-year mortality in a large national registry of acute coronary syndrome patients. Design and methods Data were extracted from the Acute Coronary Syndrome Israeli Survey national surveys between 2006-2013. A total of 6551 patients discharged with a diagnosis of acute coronary syndrome were included. Results Referral to cardiac rehabilitation following an acute coronary syndrome increased from 38% in 2006 to 57% in 2013 ( p for trend < 0.001). Multivariate modeling identified the following independent predictors for non-referral: 2006 survey, older age, female sex, past stroke, heart or renal failure, prior myocardial infarction, minority group, and lack of in-hospital cardiac rehabilitation center (all p < 0.01). Kaplan-Meier survival analyses showed one-year survival rates of 97% vs 92% in patients referred for cardiac rehabilitation as compared to those not referred (log-rank p < 0.01). Multivariate analysis showed that referral for cardiac rehabilitation was associated with a 27% mortality risk reduction at one-year follow-up ( p = 0.03). Consistently, a 32% lower one-year mortality risk was evident in a propensity score matched group of 3340 patients (95% confidence interval 0.48-0.95, p = 0.02). Conclusions Over the past decade there was a significant increase in cardiac rehabilitation referral following an acute coronary syndrome. However, cardiac rehabilitation is still under-utilized in important high-risk subsets of this population. Patients referred to cardiac rehabilitation have a lower adjusted mortality risk.

Should Men who have sex with Men be allowed to donate blood in Israel?

BACKGROUND: The present permanent deferral policy in Israel for MSM was established in 1977 and was based on the previous (now outdated) USA Food and Drug Administration standards. This study analyses epidemiological data regarding blood donations among MSM, in order to estimate the risk for HIV transfusion transmitted infection (TTI) if the policy is changed to allow at-risk MSM to donate blood. METHODS: An Excel based spreadsheet model integrated demographic, epidemiological data from the HIV National Register, laboratory, blood donation and testing data in order to calculate TTI due to false-negatives in known HIV+ donors, windows period donations, asymptomatic carriers and laboratory misclassification errors. A sensitivity analysis of our estimated TTIs for deferral periods for MSM was performed based on a literature review regarding this overall policy issue worldwide. RESULTS: MSM in Israel have a considerably higher relative risk (RR) of both prevalence (115) and incidence (143) of being HIV+ than persons without a risk factor. Allowing MSM to donate blood, without any deferral period, will add an additional five HIV TTI cases over the next decade. Imposition of a 1 or 5 years deferral of abstinence will increase the number of HIV TTI cases only by 0.10 and 0.05 cases, respectively. CONCLUSION: A 1 year deferral period for blood donations from MSM in Israel is recommended.

Near real-time space-time cluster analysis for detection of enteric disease outbreaks in a community setting.

OBJECTIVES: To enhance timely surveillance of bacterial enteric pathogens, space-time cluster analysis was introduced in Israel in May 2013. METHODS: Stool isolation data of Salmonella, Shigella, and Campylobacter from patients of a large Health Maintenance Organization were analyzed weekly by ArcGIS and SaTScan, and cluster results were sent promptly to local departments of health (LDOHs). RESULTS: During eighteen months, we identified 52 Shigella sonnei clusters, two Salmonella clusters, and no Campylobacter clusters. S. sonnei clusters lasted from one to 33 days and included three to 30 individuals. Thirty-one (60%) of the S. sonnei clusters were known to LDOHs prior to cluster analysis. Clusters not previously known by the LDOHs prompted epidemiologic investigations. In 31 of the 37 (84%) confirmed clusters, educational institutes (nursery schools, kindergartens, and a primary school) were involved. CONCLUSIONS: Cluster analysis demonstrated capability to complement enteric disease surveillance. Scaling up the system can further enhance timely detection and control of outbreaks.

Elevated Triglyceride Level Is Independently Associated With Increased All-Cause Mortality in Patients With Established Coronary Heart Disease: Twenty-Two-Year Follow-Up of the Bezafibrate Infarction Prevention Study and Registry.

BACKGROUND: The independent association between elevated triglycerides and all-cause mortality among patients with established coronary heart disease is controversial. The aim of this study was to investigate this association in a large cohort of patients with proven coronary heart disease. METHODS AND RESULTS: The study cohort comprised 15 355 patients who were screened for the Bezafibrate Infarction Prevention (BIP) trial. Twenty-two-year mortality data were obtained from the national registry. Patients were divided into 5 groups according to strata of fasting serum triglycerides: (1) low-normal triglycerides (<100 mg/dL); (2) high-normal triglycerides (100-149 mg/dL); (3) borderline hypertriglyceridemia triglycerides (150-199 mg/dL); (4) moderate hypertriglyceridemia triglycerides (200-499 mg/dL); (5) severe hypertriglyceridemia triglycerides (≥500 mg/dL). Age- and sex-adjusted survival was 41% in the low-normal triglycerides group than 37%, 36%, 35%, and 25% in groups with progressively higher triglycerides (P<0.001). In an adjusted Cox-regression for various covariates including high-density lipoprotein cholesterol, each 1 unit of natural logarithm (Ln) triglycerides elevation was associated with a corresponding 6% (P=0.016) increased risk of 22-year all-cause mortality. The 22-year mortality risk for patients with severe hypertriglyceridemia was increased by 68% when compared with patients with low-normal triglycerides (P<0.001). CONCLUSIONS: In patients with established coronary heart disease, higher triglycerides levels are independently associated with increased 22-year mortality. Even in patients with triglycerides of 100 to 149 mg/dL, the elevated risk for death could be detected than in patients with lower triglycerides levels, whereas severe hypertriglyceridemia denotes a population with particularly increased mortality risk.

Causality Assessment of Serious Neurologic Adverse Events Following bOPV National Vaccination Campaign in Israel.

BACKGROUND: During 2013-2014 Israel experienced a continuous circulation of wild poliovirus type 1 (WPV1) but with no clinical cases. WPV1 circulation was gradually terminated following a national vaccination campaign of bivalent oral poliovirus vaccine (bOPV) for 943,587 children < 10 years. Four cases of children with neurological manifestations that appeared following bOPV vaccinations were reported during the campaign: three of Guillain-Barré syndrome (GBS) and one of acute disseminated encephalomyelitis (ADEM). OBJECTIVES: To present an analysis of these cases, the rapid response and the transparent publication of the results of this analysis. METHODS: The clinical, laboratory and epidemiological data of these four patients were available during the analysis. In addition, data regarding the incidence of GBS and ADEM during previous years, and reported cases of acute flaccid paralysis (AFP) and the incidence of Campylobacter jejuni enteritis were collected from the Epidemiology Department of the Israel Ministry of Health. RESULTS: The incidence of GBS among bOPV-vaccinated children was not higher than among bOPV-unvaccinated children. For all the cases reviewed the "incubation period" from vaccination to the event was longer than expected and other more plausible causes for the neurologic manifestations were found. There is no evidence in the literature of a causal relationship between bOPV and ADEM. CONCLUSIONS: There was no association between the bOPV vaccine and the reported neurological manifestations. We believe that our experience may assist other public health professionals when confronting a similar problem of alleged side effects during a mass medical intervention.

The association between admission systolic blood pressure of heart failure patients with preserved systolic function and mortality outcomes.

INTRODUCTION: Heart failure is a major cause of death and disability and poses a significant public health concern. Approximately half of the patients admitted with heart failure, have preserved left ventricular ejection fraction. The association between systolic blood pressure (SBP) and long-term outcome in this group has not been well established. AIM: The aim of our study is to evaluate the association between admission SBP and short term and long-term mortality outcomes in patients with heart failure and preserved systolic function. METHODS: 1230 consecutive patients presenting with preserved left ventricular (LV) systolic function (defined as an LV ejection fraction ≥40%) were included in this survey. Patients were divided into quartiles according to admission SBP: low admission SBP (<127mmHg), intermediate admission SBP (128-145mmHg), high admission SBP (146-170mmHg) and very-high admission SBP (>170mmHg). Primary outcome included in hospital, one and four year mortality rates. RESULTS: Elevated admission SBP was found to be associated with improved short and long-term mortality (HR=0.25 95% CI - 0.09-0.7, p=0.007 and HR=0.7 95% CI - 0.56-0.88, p=0.002 for the highest versus low SBP group, respectively). This finding was most notable in patients with acute heart failure and patients with ejection fraction≥50%. CONCLUSION: Elevated admission SBP is associated with a favorable short and long-term outcome in patients with heart failure and preserved systolic function. KEY MESSAGE: Low admission SBP is an independent predictor for short and long-term mortality in patients with HF and PSF.

The Israeli public health response to wild poliovirus importation.

In 2013, a silent wild poliovirus type 1 importation and sustained transmission event occurred in southern Israel. With the aim of preventing clinical poliomyelitis and ensuring virus re-elimination, the public health response to the importation event included intensification of clinical and environmental surveillance activities, enhancement of vaccine coverage, and supplemental immunisation with a bivalent oral polio vaccine against wild poliovirus types 1 and 3. A national campaign launched in August, 2013, resulted in vaccination of 943,587 children younger than 10 years (79% of the eligible target population). Expanded environmental surveillance (roughly 80% population coverage) documented a gradual disappearance of wild poliovirus type 1 in the country from September, 2013, to April, 2014. No paralytic poliomyelitis case was detected. A prompt extensive and coordinated national public health response, implemented on the basis of evidence-based decision making, successfully contained this serious importation and sustained transmission event of wild poliovirus to Israel. On April 28, 2015, WHO officially declared Israel as a polio-free country.

The association between elevated admission systolic blood pressure in patients with acute coronary syndrome and favorable early and late outcomes.

In patients with acute coronary syndrome (ACS), the predictive potential of admission systolic blood pressure (SBP) on early and late outcomes is not entirely clear. We investigated the association between admission SBP in patients hospitalized for ACS and subsequent morbidity and mortality in a real world setting. The study population comprised 7645 ACS patients enrolled in the Acute Coronary Syndromes Israeli Survey (ACSIS) between 2002 and 2010. We analyzed the association between admission SBP, and the rates of 7-day and 1-year all-cause mortality and of 30-day major cardiovascular adverse events (MACE). Admission SBP was categorized as low (<110 mm Hg), normal (110-140 mm Hg), high (141-160 mm Hg), and very high (>160 mm Hg). Compared with patients with normal admission SBP, those with low SBP had a significantly increased hazard ratios (HRs) for 7-day and 1-year mortality, and MACE of 2.37, 1.92, and 1.51, respectively (all P < .001). In contrast, patients with very high admission SBP had significantly decreased HRs for 7-day and 1-year mortality, and MACE of 0.46, 0.65, and 0.84, respectively (P = .004, <.001, and .07, respectively). In patients with ACS, elevated admission SBP is associated with favorable early and late outcomes.

Artemether-lumefantrine compared to atovaquone-proguanil as a treatment for uncomplicated Plasmodium falciparum malaria in travelers.

Atovaquone-proguanil (AP) and artemether-lumefantrine (AL) are both treatments for uncomplicated Plasmodium falciparum malaria, but comparative clinical trials are lacking. We performed a retrospective analysis, comparing treatment failure and fever clearance time in non-immune travelers with uncomplicated P. falciparum malaria, treated with AP or AL. Sixty-nine patients were included during 2001-2013: 44 in the AP group and 25 in the AL group. Treatment failure was observed in 6 of 44 (13.6%) and 1 of 25 (4.0%) patients in the AP and AL groups, respectively. Six treatment failures were observed in travelers from West Africa. Fever clearance time was 44 ± 23 h in AL group versus 77 ± 28 h in AP group, (P < 0.001). Hospitalization time was significantly shorter in the AL group; 3.8 + 1.3 versus 5.1 + 2.8 days in the AP group (P = 0.04) In conclusion, travelers with uncomplicated P. falciparum malaria recover faster on AL than on AP. The AL should probably be the drug of choice for this population.

Chronic illnesses in travelers to developing countries.

BACKGROUND: Data regarding travelers with chronic illnesses (TCI) traveling to developing countries is limited. METHODS: A retrospective cohort study of travelers. We analyzed demographics, travel destinations, travel dates and duration, as well as the medical history (chronic illnesses, chronic medications, and allergies) of the travelers. RESULTS: Of 16,681 travelers evaluated, 3046 (18%) were TCI, of who, 2221 (13%) were taking chronic medications. The percentage of TCI ranged from 4% in the first decade of life to 65% in the 8th decade. The highest number of TCI (1085) was among the 20­30 years age group. The median age (IQR) of TCI was 39.0 (23.1­58.2), compared to 24.2 (22.0­32.1) years, of healthy travelers (p < 0.001). The major pre-existing medical conditions among TCI were endocrine/metabolic (38%), cardiovascular (26%) and pulmonary illnesses (16%). Within age groups, no difference was found in itinerary and other travel characteristics. However, 20­30 years old TCI, who were using chronic medications had significantly shorter travel duration (P < 0.001). CONCLUSIONS: TCI form a significant proportion of travelers among all age groups and travel destinations. Chronic illnesses appear to have little impact on travel itinerary and characteristics, but chronic medication use is associated with shorter travel duration to developing countries.

Laboratory challenges in response to silent introduction and sustained transmission of wild poliovirus type 1 in Israel during 2013.

Wild poliovirus type 1 (WPV1) introduction into southern Israel in early 2013 was detected by routine environmental surveillance. The virus was identified genetically as related to the South Asian (SOAS) R3A lineage endemic to Pakistan in 2012. Intensified, high-throughput environmental surveillance using advanced molecular methods played a critical role in documenting and locating sustained transmission throughout 2013 and early 2014 in the absence of any acute flaccid paralysis. It guided the public health responses, including stool-based surveillance and serosurveys, to determine the point prevalence in silent excretors and measured the effect of vaccination campaigns with inactivated polio vaccine and bivalent oral polio vaccine on stopping transmission.