National epidemiology of culture-confirmed brucellosis in Israel, 2004-2022.

Brucellosis, a global zoonosis, is endemic in Israel. We used a national database of culture-confirmed cases (2004-2022) to analyse the trends of brucellosis. Of 2,489 unique cases, 99.8% were bacteraemic, 64% involved males, and the mean age was 30.5 years. Brucella melitensis was the dominant species (99.6%). Most cases occurred among the Arab sector (84.9%) followed by the Jewish (8.5%) and Druze (5.5%) sectors. The average annual incidence rates overall and for the Arab, Druze, and Jewish sectors were 1.6/100,000, 6.6/100,000, 5.5/100,000, and 0.18/100,000, respectively. The annual incidence rates among the Arab (incidence rate ratio (IRR) = 36.4) and the Druze (IRR = 29.6) sectors were significantly higher than among the Jewish sector (p < 0.001). The highest incidence rates among the Arab sector occurred in the South District, peaking at 41.0/100,000 in 2012. The frequencies of B. melitensis isolated biotypes (biotype 1 - 69.1%, biotype 2 - 26.0%, and biotype 3 - 4.3%) differed from most Middle Eastern and European countries. A significant switch between the dominant biotypes was noted in the second half of the study period. Efforts for control and prevention should be sustained and guided by a One Health approach mindful of the differential trends and changing epidemiology.

The optimisation of Salmonella surveillance programmes for pullet and layer farms using local farm density as a risk factor.

Human salmonellosis cases are often caused by Salmonella serovars Enteritidis and Typhimurium and associated with the consumption of eggs and egg products. Many countries therefore implemented general surveillance programmes on pullet and layer farms. The identification of risk factors for Salmonella infection may be used to improve the performance of these surveillance programmes. The aims of this study were therefore to determine 1) whether local farm density is a risk factor for the infection of pullet and layer farms by Salmonella Enteritidis and Typhimurium and 2) whether the sampling effort of surveillance programmes can be reduced by accounting for this risk factor, while still providing sufficient control of these serovars. We assessed the importance of local farm density as a risk factor by fitting transmission kernels to Israeli surveillance data during the period from June 2017 to April 2019. The analysis shows that the risk of infection by serovars Enteritidis and Typhimurium significantly increased if infected farms were present within a radius of approximately 4 km and 0.3 km, respectively. We subsequently optimized a surveillance programme that subdivided layer farms into low and high risk groups based on the local farm density with and allowed the sampling frequency to vary between these groups. In this design, the pullet farms were always sampled one week prior to pullet distribution. Our analysis shows that the risk-based surveillance programme is able to keep the between-farm R0 of serovars Enteritidis and Typhimurium below 1 for all pullet and layer farms, while reducing the sampling effort by 32% compared to the currently implemented surveillance programme in Israel. The results of our study therefore indicate that local farm density is an important risk factor for infection of pullet and layer farms by Salmonella Enteritidis and Typhimurium and can be used to improve the performance of surveillance programmes.

Cryptosporidium parvum gp60 subtypes in diarrheic lambs and goat kids from Israel.

Cryptosporidium parvum is the second-most prevalent Cryptosporidium species that infects humans worldwide. In European countries, it is the most prevalent species in sheep, suggesting that these animals are a source of zoonotic infection. Preweaned lambs and goats are particularly susceptible to infection by the parasite and may suffer from severe diarrhea whilst excreting large quantities of infectious oocysts. Fifty fecal samples from preweaned lambs and goats with diarrhea from 35 farms across Israel, found to be Cryptosporidium-positive by microscopy, were tested by PCR and sequence analyses to determine the infective species and subtypes. Cryptosporidium parvum DNA was detected in most samples from both lambs and goats (46/50). Cryptosporidium xiaoi DNA was detected in three samples from kids, with co-infection detected in a single sample. Eleven different C. parvum subtypes were found, 10 in lambs and 5 in goats. All subtypes were from the IIa and IId subtype families, with subtypes IIdA20G1 and IIaA15G2R1 being the most prevalent and widespread. These subtypes were previously found in calves and humans in Israel and are considered the most prevalent C. parvum subtypes in small ruminants globally. These results underline the zoonotic potential of C. parvum from small ruminants and the high subtype diversity compared to previous reports from other Middle Eastern countries. In addition, this is the first report of C. xiaoi in Israel.

Oral and fecal polio vaccine excretion following bOPV vaccination among Israeli infants.

INTRODUCTION: Inactivated polio virus (IPV) vaccinations are a mainstay of immunization schedules in developed countries, while oral polio vaccine (OPV) is administered in developing countries and is the main vaccine in outbreaks. Due to circulating wild poliovirus (WPV1) detection in Israel (2013), oral bivalent polio vaccination (bOPV) was administered to IPV primed children and incorporated into the vaccination regimen. OBJECTIVES: We aimed to determine the extent and timeframe of fecal and salivary polio vaccine virus (Sabin strains) shedding following bOPV vaccination among IPV primed children. METHODS: Fecal samples were collected from a convenience sample of infants and toddlers attending 11 Israeli daycare centers. Salivary samples were collected from infants and toddlers following bOPV vaccination. RESULTS: 398 fecal samples were collected from 251 children (ages: 6-32 months), 168 received bOPV vaccination 4-55 days prior to sample collection. Fecal excretion continued among 80 %, 50 %, and 20 %, 2, 3, and 7 weeks following vaccination. There were no significant differences in the rate and duration of positive samples among children immunized with 3 or 4 IPV doses. Boys were 2.3-fold more likely to excrete the virus (p = 0.006). Salivary shedding of Sabin strains occurred in 1/47 (2 %) and 1/49 (2 %) samples 4, and 6 days following vaccination respectively. CONCLUSIONS: Fecal detection of Sabin strains among IPV-primed children continues for 7 weeks; additional doses of IPV do not augment intestinal immunity; limited salivary shedding occurs for up to a week. This data can enhance understanding of intestinal immunity achieved by different vaccination schedules and guide recommendations for contact precautions of children following bOPV vaccination.

High infection rates of Toxoplasma gondii in cattle, sheep and pigs from Israel.

Toxoplasma gondii is an obligate intracellular parasite belonging to the phylum Apicomplexa, which causes the zoonotic disease toxoplasmosis. T. gondii infects almost all warm blood animals. Generally, infected animals are asymptomatic and remain infected for life. Infection of humans occurs by consumption of infected undercooked meat or contaminated vegetables, fruit and water. The aim of this study was to evaluate the prevalence and seroprevalence of T. gondii in livestock in Israel. For the serological screening we investigated the presence of antibodies against T. gondii in sera using the indirect fluorescent antibody test (IFAT). Molecular screening was preformed using conventional PCR and nested PCR for the detection of T. gondii DNA in tissue samples. Serum samples of 249 cattle and 138 sheep were collected from farms. This serological survey showed high seroprevalence with seropositivity of 29 % in cattle and 33 % in sheep. In addition, 526 paired sera and tissue samples from cattle, sheep and pigs were obtained in slaughterhouses. The serological prevalence of T. gondii in healthy animals intended for human consumption was 29.4 % in cattle, 26.1 % in sheep and 8.1 % in pigs. The molecular detection of T. gondii in the tissue samples was 7.5 % in cattle, 7.3 % in sheep and 6.3 % in pigs. Considering the combined positive results from both serological and molecular assays, exposure to or infection with the parasite was present in 26.2 % of the samples (33.8 % in cattle, 30.3 % in sheep, 12.5 % in pigs). The prevalence of T. gondii in pigs was significantly lower compared to that of cattle and sheep (P < 0.001). All PCR positive samples from animals and 12 human positive samples were genotyped using a restriction fragment length polymorphism (PCR-RFLP) method. The results showed the existence of atypical genotypes in the majority of the samples and no correlation between animals and human samples could be determined from this study. Widespread exposure to T. gondii in Israel with the presence of parasite DNA in meat from cattle, sheep and pigs meant for human consumption was found.

The association between natural drinking water sources and the emergence of zoonotic leptospirosis among grazing beef cattle herds during a human outbreak.

Leptospirosis is a zoonotic bacterial disease associated with water abundance in tropical and temperate climate zones. Bacterial spread may also occur in dry and warm weather conditions when humans and animals are forced to share depleted water sources. In such settings, farm animals such as beef cattle, which may be present in large numbers in natural water sources, can play a major role in disease spread. However, the risk factors for their infection and the potential control measures to prevent the disease spread have not been adequately studied. In the face of an emerging human leptospirosis outbreak in the dry and warm Israeli 2018 summer, we tested seropositivity to Leptospira serovar Pomona in grazing beef cattle and wild boars located in proximity to the contaminated streams. Additionally, we used the natural setting of the outbreak to identify risk factors for seropositivity in beef cattle. We found high seropositivity to serovar Pomona in grazing beef cattle (233/845), and in wild boars (7/13). Seropositivity was significantly associated with beef cattle drinking from natural water sources compared to beef cattle drinking from water troughs with fresh water supply (Multivariable logistic regression; odds ratio = 18.6, 95% confidence interval = 3-116, p-value<0.01). One Health approach is necessary for mitigating zoonotic Leptospira infections, in which interactions between humans, animals, and the environment play a major role. As the global warming crisis results in severe climate changes, dry and warm weather conditions may become more common worldwide. Under such conditions, reducing inter-species interactions in contaminated natural water sources is essential for protecting public health. Our study demonstrates the role of natural water as a source for beef cattle infection and disease spread. Furthermore, we suggest using water troughs with freshwater supply for preventing future outbreaks in animals and humans in such settings.

Cryptosporidium parvum subtypes from diarrheic dairy calves in Israel.

Cryptosporidium are protozoan parasites with worldwide distribution, infecting a wide range of terrestrial and aquatic animals, as well as humans. Cryptosporidium parvum is the most important zoonotic species and is the primary cause of cryptosporidiosis in preweaned calves, a highly prevalent, economically important disease. Extensive subtyping of C. parvum from infected humans and animals has expanded current understanding of the parasites' epidemiology. Israel has a highly developed dairy sector with intensive, zero-grazing operations. While C. parvum has been found in dairy calves throughout the country, and subtype data from human patients have also been published, subtype data from animals, and in particular preweaned ruminants, are lacking. We carried out an initial study of Cryptosporidium species and subtypes from preweaned diarrheic calves. Cryptosporidium species were determined in 71 fecal samples from 43 different dairy farms using 18S rRNA PCR, and subtyping of C. parvum based on the 60-kDa glycoprotein (gp60) sequences was done on one sample per farm. C. parvum was the only species found, with eight different subtypes belonging to the zoonotic IIa and IId families. Subtype IIaA15G2R1 was the most prevalent and widespread, found in 50% of the farms over a wide geographical distribution. Our results confirm the presence of subtypes IIaA15G2R1 and IIdA20G1, which were previously found in human patients in Israel, also in Israeli calves. In addition, subtype IIaA12G1R1 is reported here for the first time in an animal. These findings demonstrate the value of monitoring C. parvum subtypes in animal samples, and suggest that the role of calves as well as other young ruminants in the transmission of zoonotic cryptosporidiosis in Israel should be further studied.

Inferring Numbers of Wild Poliovirus Excretors Using Quantitative Environmental Surveillance.

Response to and monitoring of viral outbreaks can be efficiently focused when rapid, quantitative, kinetic information provides the location and the number of infected individuals. Environmental surveillance traditionally provides information on location of populations with contagious, infected individuals since infectious poliovirus is excreted whether infections are asymptomatic or symptomatic. Here, we describe development of rapid (1 week turnaround time, TAT), quantitative RT-PCR of poliovirus RNA extracted directly from concentrated environmental surveillance samples to infer the number of infected individuals excreting poliovirus. The quantitation method was validated using data from vaccination with bivalent oral polio vaccine (bOPV). The method was then applied to infer the weekly number of excreters in a large, sustained, asymptomatic outbreak of wild type 1 poliovirus in Israel (2013) in a population where >90% of the individuals received three doses of inactivated polio vaccine (IPV). Evidence-based intervention strategies were based on the short TAT for direct quantitative detection. Furthermore, a TAT shorter than the duration of poliovirus excretion allowed resampling of infected individuals. Finally, the method documented absence of infections after successful intervention of the asymptomatic outbreak. The methodologies described here can be applied to outbreaks of other excreted viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), where there are (1) significant numbers of asymptomatic infections; (2) long incubation times during which infectious virus is excreted; and (3) limited resources, facilities, and manpower that restrict the number of individuals who can be tested and re-tested.

Data Empowerment of Decision-Makers in an Era of a Pandemic: Intersection of "Classic" and Artificial Intelligence in the Service of Medicine.

BACKGROUND: The COVID-19 outbreak required prompt action by health authorities around the world in response to a novel threat. With enormous amounts of information originating in sources with uncertain degree of validation and accuracy, it is essential to provide executive-level decision-makers with the most actionable, pertinent, and updated data analysis to enable them to adapt their strategy swiftly and competently. OBJECTIVE: We report here the origination of a COVID-19 dedicated response in the Israel Defense Forces with the assembly of an operational Data Center for the Campaign against Coronavirus. METHODS: Spearheaded by directors with clinical, operational, and data analytics orientation, a multidisciplinary team utilized existing and newly developed platforms to collect and analyze large amounts of information on an individual level in the context of SARS-CoV-2 contraction and infection. RESULTS: Nearly 300,000 responses to daily questionnaires were recorded and were merged with other data sets to form a unified data lake. By using basic as well as advanced analytic tools ranging from simple aggregation and display of trends to data science application, we provided commanders and clinicians with access to trusted, accurate, and personalized information and tools that were designed to foster operational changes and mitigate the propagation of the pandemic. The developed tools aided in the in the identification of high-risk individuals for severe disease and resulted in a 30% decline in their attendance to their units. Moreover, the queue for laboratory examination for COVID-19 was optimized using a predictive model and resulted in a high true-positive rate of 20%, which is more than twice as high as the baseline rate (2.28%, 95% CI 1.63%-3.19%). CONCLUSIONS: In times of ambiguity and uncertainty, along with an unprecedented flux of information, health organizations may find multidisciplinary teams working to provide intelligence from diverse and rich data a key factor in providing executives relevant and actionable support for decision-making.

Temporal trends of tilapia lake virus disease in Israel, 2017-2018.

Tilapia lake virus (TiLV) is an emerging viral disease that affects several tilapia species in different countries since 2014. In 2017-2018, 129 samples were collected from 14 tilapia farms in Israel. Ninety samples represented mortality events (ME), and 39 were used as control samples (CS). RT-qPCR was performed on 89 and 39 duplicate brain and liver tissue samples from ME samples and CS, respectively. TiLV was diagnosed in 37 (41.6%) ME, while only two of the CS samples (5%) were positive for TiLV (OR = 13.2, 95% CI = 3.0-58.1). Additional RT-PCR was performed on positive samples, and amplified products were sequenced. Maximum likelihood phylogenetic analysis of segment-3 revealed three distinct clades: the first clade (A) includes 25 sequences of TiLV, detected previously in Israel (2011), Ecuador (2012), Egypt (2015), Thailand (2015-2019), India (2017), Peru (2018) and USA (2018-2019) and 11 sequences of TiLV from the current study (2017-2018); the second clade (B) includes only four sequences from Thailand (2018) and Bangladesh (2017 and 2019); and a third clade (C) which includes a single sequence from Bangladesh (2019). Out of the 39 sequences included in clade A, 14 closely related sequences of TiLV from the current study (2018) formed a distinctive sub-clade (IL-2018). Mann-Whitney U test showed differences in the distribution of survival rates between Israeli sequences (from 2011, 2017 and 2018) of clade A (p = 0.004) and Israeli sequences (from 2018 solely) of sub-clade IL-2018. The average survival rates of clade A and sub-clade IL-2018 were 58.1% (SD = 21.5) and 31.2% (SD = 25.6), respectively. This is one of only few field studies which show direct association of TiLV with mortality events in tilapia farms. The decrease in survival rate in the newly evolved clade might raise concern regarding virus evolution towards increased virulence, which should be further explored.

Population seroprotection against hepatitis a virus in Israel 18 years after introduction of inactivated vaccine into the routine childhood vaccination schedule.

Vaccine against Hepatitis A virus (HAV) is part of the routine vaccination schedule in Israel since 1999. As of 2016, new recruits to the Israel Defense Forces should have been vaccinated in their childhood. This sero-survey aimed to determine immunity against HAV 18 years after childhood vaccination, and to re-evaluate the need for HAV vaccination booster upon recruitment. Two populations were studied: soldiers who were recruited during 2011-2012, who belonged to birth cohorts before childhood vaccination (BCV) was introduced; and recruits from 2017, who belonged to birth cohorts after childhood vaccination (ACV) was introduced. Data on 339 BCV recruits and 295 ACV recruits were analyzed. Seropositivity was 35% in the BCV group and 68% in the ACV group (P < 0.0001). Seropositivity rates among ACV subjects enable evaluation of the vaccination program's impact on the population. Our findings do not support discontinuation of HAV vaccination of at risk groups until further evaluation.

Tilapia lake virus disease: Phylogenetic analysis reveals that two distinct clades are circulating in Israel simultaneously.

Tilapia lake virus (TiLV) is an emerging viral disease that affects several tilapia species in different countries since 2014. In 2017-2018, 129 samples were collected from 14 tilapia farms in Israel. Ninety samples represented TiLV-suspected cases (TSC), and 39 were used as control samples (CS). RT-qPCR was performed on 89 and 39 duplicate brain and liver tissue samples from TSC samples and CS, respectively. TiLV was diagnosed in 37 (40.1%) of TSC, and two of the CS samples (5%) were also positive for TiLV. Additional validation RT-PCR was performed on positive samples, and amplified products were sequenced. Maximum-likelihood phylogenetic analysis of segment-3 of 25 selected sequences revealed two distinct clades: one virtually identical to sequences from India and the second closely related to isolates from Ecuador, Thailand, Egypt and Peru, apparently imported to Israel from Thailand. Thus, our results indicate that at least two distinct clades of TiLV are circulating in Israel simultaneously. As of today, the number of TiLV sequences available in free publicly accessible databases is limited. Nevertheless, our study provides new molecular epidemiology baseline for further epidemiological studies of TiLV.

Burden and risk factors of Shigella sonnei shigellosis among children aged 0-59 months in hyperendemic communities in Israel.

OBJECTIVES: Ultraorthodox Jewish populations living in towns with good sanitary infrastructure but with conditions of crowding have been the epicenter of Shigella sonnei shigellosis outbreaks. In this study, the incidence and risk factors of S. sonnei shigellosis in children living in an ultraorthodox community were determined. METHODS: Data for the years 2000-2013 for all reported culture-proven S. sonnei shigellosis cases in children aged 0-59 months in the city of Elad were compared with data for the rest of the sub-district. Environmental factors obtained through parental interviews were evaluated for 78 incident cases of S. sonnei shigellosis and 141 community controls, matched by age, sex, and neighborhood. Conditional logistic regression models were performed. RESULTS: Cyclic epidemics of S. sonnei shigellosis occurred every 2 years. The mean annual incidence was 10.0 per 1000 children in Elad (95% confidence interval 7.9-12.6) vs. 3.8 per 1000 children (95% confidence interval 3.3-4.4) in the sub-district (p<0.001). Concurrent diarrheal disease in family members, having the same person in the daycare center responsible for food handling and changing diapers, and more rooms and sinks in the center, were positively associated with S. sonnei shigellosis, while children's hand-washing before meals was inversely associated. CONCLUSIONS: The burden of S. sonnei shigellosis in ultraorthodox communities is high. Enhanced hygiene interventions are required for epidemic control.

Measles Outbreak in a Highly Vaccinated Population - Israel, July-August 2017.

On August 6, 2017, the Israeli Defense Force Public Heath Branch (IDFPHB) was notified of two suspected measles cases. IDFPHB conducted an epidemiologic investigation, which identified nine measles cases in a population with high measles vaccination coverage. All measles patients had signs and symptoms consistent with modified measles (i.e., less severe disease with milder rash, fever, or both, with or without other mild typical measles symptoms). A total of 1,392 contacts were identified, and 162 received postexposure prophylaxis (PEP) with measles-mumps-rubella (MMR) vaccine; the remaining contacts were followed for 21 days (one incubation period). No tertiary cases were identified.

Transmission tree of the highly pathogenic avian influenza (H5N1) epidemic in Israel, 2015.

The transmission tree of the Israeli 2015 epidemic of highly pathogenic avian influenza (H5N1) was modelled by combining the spatio-temporal distribution of the outbreaks and the genetic distance between virus isolates. The most likely successions of transmission events were determined and transmission parameters were estimated. It was found that the median infectious pressure exerted at 1 km was 1.59 times (95% CI 1.04, 6.01) and 3.54 times (95% CI 1.09, 131.75) higher than that exerted at 2 and 5 km, respectively, and that three farms were responsible for all seven transmission events.

A Combined Morphometric and Molecular Approach to Identifying Metacercariae of Euclinostomum heterostomum (Digenea: Clinostomidae).

Metacercariae of species of Euclinostomum have been found encysted in kidney, liver, and muscles of several fish species, while adults occur in the mouth, pharynx, larynx, trachea, and upper esophagus of fish-eating birds. The aim of this work was to gather molecular and morphological data from the type species, Euclinostomum heterostomum, as a starting point for needed revisions of the genus. Metacercariae were collected from cichlids in Lake Kinneret, Israel, and all were identified as E. heterostomum based on morphology. This identification was further confirmed by principal components analyses that revealed no partitions in morphometric resemblance, indicating that the material represents a single species, and that the specimens were morphometrically similar to other descriptions of E. heterostomum. In phylogenetic analysis of concatenated partial internal transcribed spacer 1 and 2, 5.8S rDNA, and partial cytochrome c oxidase I barcode sequences, the isolates of Euclinostomum obtained in this study form a single, monophyletic group separate from recently published data from Euclinostomum sp. from Thailand and from Clinostomum species, which are also monophyletic. The morphological and molecular data reported in the present work can provide a useful point of reference for future studies.

Back-to-school upper respiratory infection in preschool and primary school-age children in Israel.

BACKGROUND: Increased upper respiratory infection (URI) among children at the beginning of school year is well known to parents and pediatricians. However, this phenomenon is not well documented or characterized. METHODS: Computerized datasets from a large health maintenance organization in Israel were used to calculate the weekly rates of URI among children 3-14 years old for the years 2007-2012. In addition, nasopharyngeal swabs were collected in 2010-2012 from children with URI symptoms and controls during school opening time. Swabs were tested by real-time polymerase chain reaction for the presence of respiratory viruses. RESULTS: Time-series analysis demonstrated a peak of URI in September each year. The peaks reached their height 2 weeks after school opening and returned to baseline within 4-7 weeks. The main 3 viruses detected both in URI patients and in healthy controls during the first weeks of school opening were rhinovirus, adenovirus and enterovirus. The detection rate of any respiratory virus, and of rhinovirus in particular, was significantly higher among cases than among controls (54% vs. 16%, P < 0.001 for any virus, and 35% vs. 6.0%, P < 0.01 for rhinovirus). When adjusting for age and sex cases had 5.8 times more viral detection when compared with controls. Upper respiratory symptoms were significantly more prevalent among the virus-positive cases when compared with negative ones. CONCLUSIONS: Back-to-school illness consisting of URI has a distinct epidemiological pattern demonstrating a rapid rise peaking within 2 weeks of school opening and is associated predominantly with rhinovirus.

Return of pandemic H1N1 influenza virus.

BACKGROUND: Influenza pandemics are usually caused by the re-assortment of several influenza viruses, results in the emergence of new influenza virus strains that can infect the entire population. These pandemic strains, as well as seasonal influenza viruses, are subjected to extensive antigenic change that has, so far, prevented the generation of a universal vaccine. METHODS: Samples of patients hospitalized due to infection with the pandemic H1N1 influenza virus (A(H1N1)pdm09) from 2009, when the virus first appeared, until 2013 were analyzed. RESULTS: While many patients were hospitalized in 2009 due to infection with the pandemic H1N1 influenza virus, only small percentages of patients were hospitalized later in 2010-2012. Surprisingly, however in 2012-2013, we noticed that the percentages of patients hospitalized due to the pandemic H1N1 influenza infection increased significantly. Moreover, the ages of hospitalized patients differed throughout this entire period (2009-2013) and pregnant women were especially vulnerable to the infection. CONCLUSIONS: High percentages of patients (especially pregnant women) were hospitalized in 2013 due to the A(H1N1)pdm09 infection, which may have been enabled by an antigenic drift from those which circulated at the onset of the pandemic.