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.

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.

Design and application of a core genome multilocus sequence typing scheme for investigation of Legionnaires' disease incidents.

Sequence-based typing (SBT) for Legionella pneumophila (Lp) has dramatically improved Legionnaires' disease (LD) cluster investigation. Microbial whole genome sequencing (WGS) is a promising modality for investigation but sequence analysis methods are neither standardised, nor agreed. We sought to develop a WGS-based typing scheme for Lp using de novo assembly and a genome-wide gene-by-gene approach (core genome multilocus sequence typing, cgMLST). We analysed 17 publicly available Lp genomes covering the whole species variation to define a core genome (1,521 gene targets) which was validated using 21 additional published genomes. The genomes of 12 Lp strains implicated in three independent cases of paediatric humidifier-associated LD were subject to cgMLST together with three 'outgroup' strains. cgMLST was able to resolve clustered strains and clearly identify related and unrelated strains. Thus, a cgMLST scheme was readily achievable and provided high-resolution analysis of Lp strains. cgMLST appears to have satisfactory discriminatory power for LD cluster analysis and is advantageous over mapping followed by single nucleotide polymorphism (SNP) calling as it is portable and easier to standardise. cgMLST thus has the potential for becoming a gold standard tool for LD investigation. Humidifiers pose an ongoing risk as vehicles for LD and should be considered in cluster investigation and control efforts.

Severity of pneumococcal versus non-pneumococcal acute otitis media in children.

BACKGROUND: Pneumococcal acute otitis media (AOM) has been previously considered as a more severe disease than that caused by other otopathogens, based on clinical and/or otologic scores. We sought to test this hypothesis in the pneumococcal conjugated vaccine (PCV) era. METHODS: Children <6 years who presented with 'severe' AOM episodes with middle ear fluid (MEF) cultures during 2008-2013 were retrospectively identified. 'Severe' AOM episodes were considered if tympanocentesis was required or if spontaneous otorrhea was present. Data were extracted for demographics, clinical and laboratory tests. Children were categorised according to their PCV status as 'unimmunised' or 'PCV7/PCV13 immunised' and according to their MEF culture results into the 'pneumococcal' or the 'non-pneumococcal' group. Leukocytosis was defined as white blood cells (WBC) count >15 000/µL, and elevated C-reactive protein (CRP) level was considered as >50 mg/L. RESULTS: Of 295 eligible AOM episodes, 106 (36%) were culture positive. Children in the pneumococcal group (65, 61%) had a significantly higher WBC counts and higher CRP levels, were more often <2 years old and were more prone to complicate with acute mastoiditis (AM), compared to children in the non-pneumococcal group, P = 0.03, P = 0.02, P = 0.04 and P = 0.03, respectively. In the pneumococcal group, unimmunised children had higher WBC counts when compared with PCV13-immunised children (P = 0.04), but there were no appreciable differences in CRP levels between unimmunised and PCV7/PCV13-immunised children. CONCLUSION: Pneumococcal AOM is associated with higher leukocytosis and CRP levels than non-pneumococcal AOM. Circulating Streptococcus pneumoniae strains causing 'severe' AOM in PCV13-immunised children yielded lower inflammatory responses when compared with unimmunised children.

Intensified environmental surveillance supporting the response to wild poliovirus type 1 silent circulation in Israel, 2013.

An emergency response was triggered by recovery of wild poliovirus type 1 (WPV1) of the South Asia (SOAS) lineage from sewage in southern Israel in April 2013 during routine environmental surveillance. Public health risk assessment necessitated intensification of environmental surveillance in order to facilitate countrywide monitoring of WPV1-SOAS circulation. This involved increasing sampling frequency and broadening the geographical area, for better coverage of the population at risk, as well as modifying sewage testing algorithms to accommodate a newly developed WPV1-SOAS-specific quantitative real-time RT-PCR assay for screening of RNA extracted directly from sewage concentrates, in addition to standard virus isolation. Intensified surveillance in 74 sites across Israel between 1 February and 31 August 2013 documented a sustained high viral load of WPV1-SOAS in sewage samples from six Bedouin settlements and two cities with Jewish and Arab populations in the South district. Lower viral loads and intermittent detection were documented in sampling sites representing 14 mixed communities in three of the five health districts in central and northern Israel. Environmental surveillance plays a fundamental role in routine monitoring of WPV circulation in polio-free countries. The rapid assay specific for the circulating strain facilitated implementation of intensified surveillance and informed the public health response and decision-making.

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'.

Molecular epidemiology of silent introduction and sustained transmission of wild poliovirus type 1, Israel, 2013.

Poliovirus vaccine coverage in Israel is over 90%. The last nine birth cohorts have been vaccinated exclusively with inactivated polio vaccine (IPV). However, between February and July 2013 type 1 wild poliovirus (WPV1) was detected persistently in 10 and intermittently in 8 of 47 environmental surveillance sites in southern and central Israel and in 30 stool samples collected during July from healthy individuals in southern Israel. We report results of sequence and phylogenetic analyses of genes encoding capsid proteins to determine the source and transmission mode of the virus. WPV1 capsid protein 1 nucleotide sequences were most closely related to South Asia (SOAS) cluster R3A polioviruses circulating in Pakistan in 2012 and isolated from Egyptian sewage in December 2012. There was no noticeable geographical clustering within WPV1-positive sites. Uniform codon usage among isolates from Pakistan, Egypt and Israel showed no signs of optimisation or deoptimisation. Bayesian phylogenetic time clock analysis of the entire capsid coding region (2,643 nt) with a 1.1% evolutionary rate indicated that Israeli and Egyptian WPV1-SOAS lineages diverged in September 2012, while Israeli isolates split into two sub-branches after January 2013. This suggests one or more introduction events into Israel with subsequent silent circulation despite high population immunity.

Increasing trend of HIV/AIDS among Arab and Jewish male persons in Israel, 1986-2010.

OBJECTIVES: The aim of the study was to compare the HIV/AIDS burdens in Jewish and Arab Israeli males, as HIV/AIDS affects different population groups disproportionally. METHODS: The National HIV/AIDS Registry (NHAR) was used as the source of HIV/AIDS infection records, while the Israeli Central Bureau of Statistics was used to determine group-specific disease rates. RESULTS: Between 1986 and 2010, 3499 HIV/AIDS-infected male Israelis were reported to the NHAR: 3369 (96.3%) Jews and 130 (3.7%) Arabs, with an average annual incidence of 5.5 and 0.8 per 100 000 of the population, respectively (P = 0.05). Of the Jews, 1018 (29.9%) were born in Ethiopia, while 2389 were Jews who were not Ethiopian-born (JNE). Most of the Arabs (n = 99; 74.8%) were Muslims, followed by Christians (21; 16.2%) and Druze (13; 10%). AIDS rather than HIV infection at the time of reporting was diagnosed in 568 (23.8%) of the JNE and 31 (23.8%) of the Arabs (p = 1). The most affected age group was those aged 25-34 years among the JNE and those aged 20-24 years among the Arabs, and the respective cumulative death rates were 24.9% (n = 594) and 32.5% (n = 40) (P = 0.1). The point prevalences in 2010 were 58.4 and 11.4 per 100 000 for JNE and Arabs, and in adults aged 15-59 years they were 71.5 and 26.3 per 100 000, respectively. In Muslims, Christians and Druze, the point prevalences were 4.2, 11.2 and 7.1 per 100 000, and in adults aged 15-59 years they were 22.6, 42.9 and 29.4, respectively. The most common risk group among JNE was men who have sex with men (MSM; n = 1223; 51.2%), followed by injecting drug users (n = 661; 27.7%), while among Arabs it was MSM (n = 63; 48.1%), followed by heterosexuals (n = 36; 27.3%). CONCLUSIONS: The HIV/AIDS burden in Israeli Arab males was significantly lower than that in Jews, and in both populations the most common risk group was MSM, with the proportion of MSM increasing with time.

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.

Secular and seasonal trends of infectious mononucleosis among young adults in Israel: 1978-2009.

Recent evidence that infectious mononucleosis (IM) may be sexually transmitted prompted the present analysis. Infectious mononucleosis is a notifiable disease in the Israel Defense Forces (IDF). For the present study, the archives of the IDF were reviewed for all cases of IM from January 1, 1978 to December 31, 2009, and the rates were calculated. Annual rates decreased from 2.99 cases per 1,000 in 1979 to a low of 0.38 cases per 1,000 young adults in 1987. Between 2002 and 2009, the average annual rate was 0.88 cases per 1,000, just half the average rate of 1.69 observed between 1989 and 2001. Average monthly rates varied from a low of 0.90 cases per 10,000 in February to a high of 1.50 cases per 10,000 in August. The difference in the average rates between winter (1.02 cases per 10,000 soldiers) and summer (1.29 cases per 10,000 soldiers) was significant (p < 0.01). Analysis of the long-term epidemiology of IM shows that the infection rate has varied over time, and that the disease is more prevalent in the warmer months. This seasonality trend was also observed in several STD, raising the possibility of considering this mode of transmission in IM.

Mumps outbreak in Israel's highly vaccinated society: are two doses enough?

Mumps outbreaks in recent years have given rise to questions about the effectiveness of the mumps vaccine. This study examined the epidemiological data from a recent mumps outbreak in Israel and from outbreaks in other countries with high vaccination coverage, and considered whether long-established vaccination policies designed to protect against mumps are in need of revision. Of over 5000 case patients in the Israeli outbreak, half of whom were in the Jerusalem health district, nearly 40% were aged ≥15 years and, of those whose vaccination status was known, 78% had been fully vaccinated for their age - features similar to those in recent mumps outbreaks in Europe and North America. The epidemiological and laboratory evidence suggests that many previously vaccinated adolescents and young adults are now susceptible to mumps because their vaccine-based immunity has waned. Booster vaccination programmes for those at high risk of infection during mumps outbreaks - particularly those in congregate living environments - merit priority consideration.

Humidifier-associated paediatric Legionnaires' disease, Israel, February 2012.

We report a fatal case of community-acquired Legionnaires' disease in an infant aged under six months. Epidemiological and microbiological investigations suggested that a free-standing cold water humidifier using domestic tap water contaminated with Legionella pneumophila serogroup 1 served as a vehicle for infection. These findings were corroborated by sequence-based typing (SBT). Humidifier-associated Legionnaires' disease can be prevented by appropriate control measures. This case also illustrates the emerging role of SBT in the investigation of legionellosis.

Postpartum depression and infant development up to 24 months: A nationwide population-based study.

AIMS: Postpartum depression (PPD) is the most common complication women experience after delivery. We aimed to examine the association of maternal PPD with delays in child development, in a population-based study, in the first two years of life. METHODS: A nation-wide population-based historical cohort study in the setting of the Mother and Child Health Clinics in Israel, where infants are routinely evaluated for growth and development. Data were retrieved on 96,623 infants born in 2014-2015 whose mothers had PPD screening. Logistic regressions were used to estimate the associations of PPD with the achievements of developmental milestones, controlling for potential confounders. RESULTS: PPD was identified in 4,268 mothers (4.7%). PPD was associated with delays in language skills, including the production of voices in dialogue (OR=1.88, 95% CI: 1.41-2.52) and speaking 2-3 words (OR=1.24, 95% CI: 1.13-1.37). PPD was associated with about 1.5 times increased odds of delays in personal-social skills, including reacting to voices (OR=1.43, 95% CI: 1.22-1.67) and pointing to selected objects (OR=1.47 95% CI: 1.10-1.97). Associations were also seen with delays in fine motor and adaptive skills, such as pinching (OR=1.50, 95% CI: 1.20-1.86), and gross motor skills, such as ground crawling (OR=1.36, 95% CI: 1.15-1.60). CONCLUSIONS: In this population-based large cohort study, PPD as estimated in a national screening program, was associated with delays in early child development, which were shown in all assessed domains. Future studies should confirm our results and intervention programs should be developed to effectively minimize these gaps.

Secular trends of gonorrhea in young adults in Israel: three decades of follow-up.

Recent reports of increased rates of gonorrhea initiated an analysis of secular trends of gonorrhea in a young adult population. Gonorrhea is a notifiable disease in the Israel Defense Forces. The diagnosis is based on the typical clinical presentation, relevant epidemiologic data, and positive bacteriological culture. For the present study, the archives of the Epidemiology Department were reviewed for all documented cases of gonorrhea from January 1, 1978 to December 31, 2008, and the annual and seasonal incidence rates were calculated. Annual gonorrhea rates decreased from 2.3 cases per 1,000 soldiers in 1978 to an all-time low of 0.07 cases per 1,000 soldiers in 2008, representing a 97% decline. Multi-year average monthly rates varied from a low of 5.83 cases per 100,000 population in February to a high of 8.97 cases per 100,000 in August. The difference in the person-time incidence (PTI) rates for winter (5.9 cases per 100,000 person-years) and summer (6.8 cases per 100,000 person-years) was statistically significant (p < 0.01). Analyzing the long-term epidemiology of gonorrhea has shown that the infection rate is continuously decreasing and that it appears to be more prevalent in the warmer months.

An outbreak of leptospirosis among Israeli troops near the Jordan River.

An outbreak of leptospirosis that involved 7 of a team of 27 Israeli troops occurred following a military exercise in northern Israel near the Jordan River. The organism implicated in the outbreak was Leptospira interrogans serovar Hardjo. The clinical course was uncomplicated and all patients fully recovered. There were no cases of asymptomatic infection. Military personnel should be recognized as having an occupational risk for contracting leptospirosis, especially when military activity takes place near natural water sources inhabited by cattle, taking into account the local epidemiology of this disease. Moreover, outbreaks among military personnel may serve as a sentinel for leptospiral illness in areas in which civilian exposure takes place, such as the Jordan River, which is an important site that involves immersion in the context of both pilgrimage and civilian recreational activities."Bathe and you will become clean. So he went down and immersed himself seven times in the Jordan, as Elisha had told him to do. And his flesh became clean once more like the flesh of a small child."II Kings 5:14.

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.

Nitrogen Dioxide pollution and hazardous household environment: what impacts more congenital malformations.

Nitrogen Dioxide (NO2) is a product of fuel combustion originating mainly from industry and transportation. Studies suggest an association between NO2 and congenital malformations (CM). We investigated an independent effect of NO2 on CM by adjusting to individual factors and household environment in 1024 Bedouin-Arab pregnant women in southern Israel. This population is characterised by high rates of CMs, frequent consanguineous marriages, paternal smoking, temporary housing and usage of open fire for heat cooking. Information on household risk factors was collected during an interview. Ambient measurements of 24-h average NO2 and meteorological conditions were obtained from 13 local monitors. Median value of daily NO2 measured in the area was 6.78ppb. CM was diagnosed in 8.0% (82) of offspring. Maternal NO2 exposure during the 1st trimester >8.6ppb was significantly associated with minor CM (RR=2.68, p=0.029). Major CM were independently associated with maternal juvenile diabetes (RR=9.97, p-value=0.002) and heating by open fire (RR=2.00, p-value=0.049), but not NO2 exposure. We found that NO2 emissions had an independent impact only on minor malformations, whereas major malformations depended mostly on the household environment. Antepartum deaths were associated by maternal morbidity.

Engraftment-associated hypophosphatemia--the role of cytokine release and steep leukocyte rise post stem cell transplantation.

Hypophosphatemia associated with bone marrow transplantation has been infrequently reported. The suggested mechanism is phosphate uptake by the replicating cells. Various cytokines are associated with the development of hypophosphatemia. The present study evaluated the interrelationship between cytokine release, the rise in WBC and the development of hypophosphatemia during the engraftment period. Blood samples were obtained from 60 patients undergoing peripheral blood stem cell transplant, on the day of admission and then daily from the day of transplant until discharge. Hypophosphatemia developed in 62% of the patients. The median day of minimal phosphorus level was +8 and it antedated engraftment by 2 days. There was a significant correlation between the day of minimal phosphorus level and the day of maximal WBC and a significant correlation between the fall in phosphorus level and WBC rise. IL-6 and IL-8 showed similar kinetics. Higher IL-6 and IL-8 levels were directly associated with lower phosphorus levels. In conclusion, hypophosphatemia commonly occurs in the post-transplant period. We assume that both a direct effect of cytokine release and an increased consumption by the dividing WBCs contribute to its appearance. As its occurrence usually antedates engraftment it can be used as a forerunner for WBC recovery.

[Epidemiological characteristics of outbreaks of diarrhea and food poisoning in the Israel Defense Forces in the years 1978-1995].

Acute infectious diseases of the gastrointestinal tract and food poisoning are problems of great importance in the Israel Defense Forces (IDF). They involve individual and epidemic morbidity, with impairment of health of individual soldiers and in the activities of units. Outbreaks of gastrointestinal infectious diseases must be reported to the IDF army health branch, which conducts epidemiological investigation. This study is based on data from yearly epidemiological reports for 1978-1989, and from a computerized database for the years 1990-1995. The incidence of outbreaks is characterized by an unstable trend. It was highest at the end of the 80's (68.3 per 100,000 soldiers on active duty) and lowest for the last 2 years (1994-1995, 36.3 per 100,000). The incidence of soldiers involved in food-borne outbreaks has been more stable, constantly declining during the course of the years. There was marked seasonality with a peak in the summer months. Sporadic morbidity was constant in 1990-1995, with a yearly attack rate of 60% in soldiers on active duty. Shigella strains were the leading cause of outbreaks until 1993, while in 1994-1995 their proportion decreased, with an increase in the proportion of Salmonella strains. As to Staphylococcus aureus, its role in causing food poisoning has been characterized by marked changes. Shigella sonnei replaced Shigella flexneri as the leading strain. 73.3% of outbreaks were small, with fewer than 40 soldiers involved, while 5.4% of outbreaks affected more than 100 soldiers. Outbreaks in which a bacterial agent was identified or which occurred in new-recruit bases were larger than those in which a bacterial agent was not identified, or which occurred in active field unit bases. In conclusion, the rates of infectious disease of the gastrointestinal tract are still high, although there has been a marked decrease since 1994. The incidence of outbreaks has also decreased, as well as the role of Shigella as a leading causative agent.

[Trends in epidemiology of hepatitis in the Israel Defense Forces-- direction over several years].

During the 50's and 60's there were large scale epidemics of hepatitis A every 3-4 years in the Israel Defense Forces. During these epidemics the annual incidence exceeded 10/1000 soldiers at risk. There has been a highly significant decrease in rates during the past 30 years. The average annual incidence of clinically identified viral hepatitis A decreased from an average of 6/1000 during the 60's to 2.5/1000 during the 70's. The decrease coincided with the introduction in the 1970's of wide-scale post-exposure prophylaxis with immune serum globulin (ISG). The incidence was further significantly reduced to 0.5-1.0/1000 with the introduction of pre-exposure prophylaxis with ISG, starting in 1978 (p < 0.001). Other factors probably played a role in accelerating the decline in morbidity, such as improvement in personal hygiene and sanitation facilities, and in waste disposal and other aspects of military environmental health. These improvements were probably more pronounced in the civilian sector, leading to decreased exposure of children to the virus and consequently a higher proportion of seronegatives at induction. Increase in the proportion of recruits without natural immunity to the virus poses greater risk, both in terms of personal morbidity as well as military operational ability. This risk, combined with problems of ISG use and availability, has propelled hepatitis A prevention policy towards the use of the new inactivated vaccines.