Search

Sensitive, specific and rapid molecular diagnosis of respiratory diseases in animals and humans is critical to facilitate appropriate control measures and treatment. Conventional polymerase chain reaction (PCR)-based molecular diagnostics requires relatively expensive equipment and trained staff, restricting its use to centralized laboratories with significant delays between sample collection and test results. Herein, we report a highly sensitive, rapid, point-of-need, two-stage-molecular test that requires minimal instrumentation and training. Our test, dubbed Penn-RAMP, combines recombinase polymerase amplification (RPA, 38 °C) and loop-mediated isothermal amplification (LAMP, 63 °C) in one tube, enabling nested, two-stage isothermal amplification. We demonstrate Penn-RAMP's efficacy by testing for two common viral respiratory diseases of chickens: infectious laryngotracheitis (ILT) and infectious bronchitis (IB) that impose great economic burden worldwide. Test results of clinical samples with our closed-tube Penn-RAMP assays concord with the gold standard quantitative PCR (qPCR) assay; with 10-fold better limit of detection than LAMP and qPCR. Our closed-tube Penn-RAMP assays have the potential to greatly reduce false negatives while requiring minimal instrumentation and training.

IntroductionUniversal vaccination of toddlers has led to very low hepatitis A (HAV) endemicity in Israel. However, sporadic outbreaks still occur, necessitating better surveillance.AimTo implement a comprehensive HAV surveillance programme.MethodsIn 2017 and 2018, sera from suspected HAV cases that tested positive for anti-HAV IgM antibodies were transferred to the Central Virology Laboratory (CVL) for molecular confirmation and genotyping. Sewage samples were collected in Israel and Palestine* and were molecularly analysed. All molecular (CVL), epidemiological (District Health Offices and Epidemiological Division) and clinical (treating physicians) data were combined and concordantly assessed.ResultsOverall, 146 cases (78 in 2017 and 68 in 2018, median age 34 years, 102 male) and 240 sewage samples were studied. Most cases (96%) were unvaccinated. In 2017, 89% of cases were male, 45% of whom were men who have sex with men (MSM). In 2018, 49% were male, but only 3% of them were MSM (p < 0.01). In 2017, 82% of cases and 63% of sewage samples were genotype 1A, phylogenetically associated with a global MSM-HAV outbreak. In 2018, 80% of cases and 71% of sewage samples were genotype 1B, related to the endemic strain previously identified in Israel and Palestine*. Environmental analysis revealed clustering of sewage and cases' sequences, and country-wide circulation of HAV.ConclusionsMolecular confirmation of HAV infection in cases and analysis of environmental samples, combined with clinical and epidemiological investigation, may improve HAV surveillance. Sequence-based typing of both clinical and sewage-derived samples could assist in understanding viral circulation.

Infectious bronchitis (IB) is a viral infection of the chicken respiratory tract that causes substantial economic burden on the industry. Simple, specific and rapid diagnosis of this disease is critical for the initiation of appropriate control measures. Conventional molecular diagnostic methods require a relatively sophisticated equipment and skilled staff. Here we describe a rapid, simple, semi-quantative, closed-tube, single-step, real-time- reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay for IB and compare our assay with quantative, reverse transcription- polymerase chain reaction (RT-qPCR). The limit of detection (LOD) of our RT-LAMP assay is 1 EID 50 / ml. Clinical evaluation of samples from diseased chickens with our RT-LAMP showed a very good concordance with RT-qPCR. Our assay enables simple, specific, rapid molecular detection and semi-quantification of the infectious bronchitis virus (IBV) in veterinary diagnostic laboratories. Furthermore, our RT-LAMP detection is carried out in a sealed tube, eliminating the risk of false-positive results in subsequent tests because of any contamination of the work area as in the case of lateral flow strip or gel electrophoresis-based amplicon detection., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In this study, we aim to assess the phytomedicinal potential of perillyl alcohol (PA), a dietary monoterpenoid, in a unilateral 6-hydroxydopamine (6-OHDA) lesion rat model of Parkinson's disease (PD). We observed that PA supplementation alleviated behavioural abnormalities such as loss of coordination, reduced rearing and motor asymmetry in lesioned animals. We also observed that PA-treated animals exhibited reduced oxidative stress, DNA fragmentation and caspase 3 activity indicating alleviation of apoptotic cell death. We found reduced mRNA levels of pro-apoptotic regulator BAX and pro-inflammatory mediators IL18 and TNFα in PA-treated animals. Further, PA treatment successfully increased mRNA and protein levels of Bcl2, mitochondrial biogenesis regulator PGC1α and tyrosine hydroxylase (TH) in lesioned animals. We observed that PA treatment blocked BAX and Drp1 translocation to mitochondria, an event often associated with the inception of apoptosis. Further, 6-OHDA exposure reduced expression of electron transport chain complexes I and IV, thereby disturbing energy metabolism. Conversely, expression levels of both complexes were upregulated with PA treatment in lesioned rats. Finally, we found that protein levels of Nrf2, the transcription factor responsible for antioxidant gene expression, were markedly reduced in cytosolic and nuclear fraction on 6-OHDA exposure, and PA increased expression of Nrf2 in both fractions. We believe that our data hints towards PA having the ability to provide cytoprotection in a hemiparkinsonian rat model through alleviation of motor deficits, oxidative stress, mitochondrial dysfunction and apoptosis.

Introduction:  Fetus in fetu (FIF) is an extremely rare condition of abnormal twinning during embryogenesis. Most publications are single case reports. We describe the combined experience of four large tertiary referral centers with FIF which were not previously reported or published, and thereby draw conclusions to establish criteria for the workup, diagnosis, and management including intraoperative risk., Materials and Methods:  A survey was forwarded to a national pediatric surgery group which includes members from all pediatric surgery centers in the country enquiring about unpublished cases of FIF encountered over a 20-year interval. The cohort was analyzed for age of presentation, type of presentation, diagnostic workup, surgical management, and outcome., Results:  From 1998 to 2018, a total of 10 FIF cases were included in the study. Mean age of presentation was 4 months. Computed tomography and ultrasound were the main preoperative diagnostic modality in our cohort. Resection of the mass was curative in nine cases. Two cases in which the FIF was in direct topographic proximity to the biliary tree suffered severe intraoperative or lethal postoperative complications., Conclusion:  Complete excision of FIF is the treatment of choice and generally results in excellent long-term quality of life. Mortality is rare and may be associated with biliary involvement and retroperitoneal right upper quadrant location of the FIF tends to be associated with increased risk in excision, and there is also a possible association with the presence of immature elements in the pathology report., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

Pertussis incidence in developed countries, including Israel, has increased over the past two decades despite the addition of two booster doses in children. However, as pertussis is characterized by a multi-annual periodicity, and since clinical diagnosis can miss cases, determining disease trends at the population level is challenging. To bridge this gap, we developed a simple statistical model to capture the temporal patterns of pertussis incidence in Israel. Our model was calibrated and tested using laboratory-confirmed cases of pertussis for the Israeli population between 1998 and 2019. The model identifies a clear four-year periodicity of pertussis incidence over the past two decades that is identical to the one observed in the pre-vaccine era. Accounting for this periodicity, the model shows a 325% increase in pertussis incidence from 2002 to 2014. These multi-year trends were interrupted shortly after the introduction of routine immunization of Tdap vaccine in pregnancy in 2015, after which we found a 59.7% (95% CI: 57.7-61.6%)decline in pertussis incidence and a 49.5% (36.0-61.6%) decline in hospitalizations compared to the model's projection. While this sharp decline cannot be fully attributed to the newly introduced vaccination policy, sharper reductions of 71.2% (65.6-76.1%) in incidence and 58.4% (39.6-72.7%) in hospitalizations, have been observed in infants of age two months and below - young infants that have yet to become vaccinated and are more likely to be protected by maternal vaccination. Our work suggests that Tdap vaccination during pregnancy is a promising policy for controlling pertussis. Furthermore, due to the stable periodicity of pertussis, public health decision-makers should invest continuous efforts in the implementation of this strategy with additional reinforcement in expected peak years., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

An outbreak of canine distemper virus in a private zoo in eastern Tennessee in July 2016 led to fatal clinical disease in 5 adult, wild-caught Linnaeus's 2-toed sloths ( Choloepus didactylus ). Clinical signs included hyporexia, lethargy, mucopurulent nasal discharge, and oral and facial ulcers. At necropsy, affected animals had crusts and ulcers on the lips, nose, tongue, and oral cavity. Microscopically, all sloths had widespread, random, hepatic necrosis; lymphoid depletion; and bronchointerstitial pneumonia. The central nervous system did not contain gross or histopathologic lesions in any of the 5 sloths, although immunoreactivity for viral antigen was present within vessel walls. Epithelial cells and histiocytes within numerous organs contained intranuclear and intracytoplasmic inclusions and occasional syncytial cells. Canine distemper virus was confirmed with immunohistochemistry and virus isolation. Viral sequencing identified the novel American-4 strain prevalent in eastern Tennessee wildlife. This is the first pathologic characterization of canine distemper virus infection in sloths (family Choloepodidae, order Pilosa) and emphasizes the significant morbidity and mortality in this species.

This study evaluated the safety of and humoral response to the Merial Recombitek ® recombinant canine distemper virus (rCDV) vaccine in maned wolves ( n = 9, age 2-9 yr). All maned wolves had prior history of annual vaccination with the Merial Purevax ® ferret rCDV vaccine. Serum neutralization (SN) to CDV was measured prior to initial vaccination with the rCDV Recombitek vaccine followed by a booster vaccination at 4-6 wk. Final SN titers were obtained at 13 wk post initial vaccination. The maned wolves developed no observable adverse side effects through the study. Pre-Recombitek vaccination SN titers ranged from negative to 1: 8. Postvaccination CDV titers ranged from negative to 1: 8, and were therefore below the range of that considered protective in domestic dogs.

Two methods for delivering a canarypox-vectored canine distemper vaccine to tigers ( Panthera tigris ) and domestic cats ( Felis catus ) were investigated. Eight tigers were divided randomly into two vaccination groups: subcutaneous injection or topical tonsillar application. Each tiger received 2 ml of canine distemper virus (CDV) vaccine (Merial Ferret Distemper Vaccine). Blood was collected from tigers on days 0, 21, 35 or 37, and 112 post-initial vaccination (PIV). Domestic cats were divided randomly into four treatment groups: saline injection (negative controls), low- and high-dose oral, and subcutaneous vaccinates. Blood was collected from domestic cats on days 0, 7, 21, and 28 and 165 or 208 PIV. Sera were tested for CDV antibodies by virus neutralization. All individuals were seronegative at the beginning of the study. One tiger vaccinated subcutaneously developed a titer of 32 by day 35, which reduced to 16 by day 112. Another tiger vaccinated by tonsillar application developed a titer of 8 on day 112. All other tigers remained seronegative. Cats that received saline injection or oral vaccination remained seronegative at each sampling time. Domestic cats vaccinated subcutaneously developed titers ranging from 4 to >128 by day 28, and those re-bled at day 166 had titers of 16 or 64. The disparity in response between domestic cats and tigers may be due to species differences or it may represent a dose-dependent effect. Subcutaneous vaccination with canarypox-vectored Purevax Ferret Distemper ® is safe and elicits persistent antibody titers in domestic cats vaccinated parenterally.

Canine distemper virus (CDV) is a highly contagious disease of wild and domestic mammals. Maintenance of CDV among wildlife plays an important role in the disease epidemiology. Wild animals, including raccoons ( Procyon lotor ) and gray foxes ( Urocyon cinereoargenteus ), serve as reservoirs of CDV and hamper the control of the disease. Recently, we discovered that at least three different CDV lineages (America-3 [Edomex], America-4, and America-5] that are genetically different from the available vaccine strains are circulating in domestic dogs in the United States. Because wildlife serve as a reservoir for the virus, it is important to determine if wildlife play a role in the maintenance and spread of these lineages. To determine the genetic characteristics of circulating strains of CDV in wildlife in various geographic regions in the United States, we studied the nucleotide sequences of the hemagglutinin (H) gene of 25 CDV strains detected in nondomestic species. The species included were free-ranging wildlife: three fishers ( Martes pennanti ), six foxes, one skunk ( Mephitis mephitis ), 10 raccoons, two wolves ( Canis lupus ), and one mink ( Neovison vison ). Strains from two species in managed care, one sloth ( Choloepus didactylus ) and one red panda ( Ailurus fulgens ), were also evaluated. Phylogenetic analysis of the H genes indicated that in addition to America-3, America-4, and America-5 lineages, there are at least two other lineages circulating in US wildlife. One of these includes CDV nucleotide sequences that grouped with that of a single CDV isolate previously detected in a raccoon from Rhode Island in 2012. The other lineage is independent and genetically distinct from other CDV strains included in the analysis. Additional genetically variable strains were detected, mainly in raccoons, suggesting that this species may be the host responsible for the genetic variability of newly detected strains in the domestic dog population.

Disruption of the tightly regulated mitochondrial dynamics and energy homeostasis leads to oxidative stress and apoptotic cell death, as observed in neurodegenerative disorders such as Parkinson's disease (PD). Polyphenolic plant derivatives have been shown to alleviate such pathological features and have been used in models of neurodegenerative disorders in previous reports. In the current study, we utilized a 6-hydroxydopamine (6-OHDA) lesioned rat model of PD to explore the protective efficacy of polyphenolic phytochemical ferulic acid (FA) against mitochondrial dysfunction and explored its effect on gene and protein expression of mitochondrial dynamics regulators dynamin-related protein 1 (Drp1)/mitofusin 2 (Mfn2) in lesioned animals. We also evaluated its effect on expression of mitochondrial biogenesis regulator PGC1α and apoptotic regulators BAX, cyt c, p53, and cleaved PARP. We found that oral FA supplementation alleviated 6-OHDA induced oxidative stress, DNA fragmentation, morphological changes, and blocked apoptotic cascade. FA also reduced mitochondrial Drp1 expression and increased gene and protein expression of PGC1α, thereby regulating expression of its downstream target Mfn2 and restoring mitochondrial dynamics in lesioned animals. Our data suggest that targeting mitochondrial dynamics through modulation of PGC1α can prove to be a potent preventive strategy against PD pathology., (© 2019 John Wiley & Sons, Ltd.)

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.

A 6-wk-old managed male Arctic wolf with lethargy, drooling, dehydration, elevated temperature, and acute onset of seizures was submitted for autopsy. The wolf had been vaccinated with a multivalent vaccine exactly 2 wk prior to presentation. Grossly, long bones were brittle and easily fractured under pressure; the intestinal contents were mucoid and yellow. Histologically, there was widespread lymphoid and hematopoietic necrosis, failure of endochondral ossification within long bones, as well as intranuclear and intracytoplasmic inclusions in various tissues and cell types. Canine distemper virus was detected in numerous tissues by IHC and confirmed by RT-rtPCR and sequencing as an American-4 strain, an emerging strain in domestic dogs and wildlife species in the southeastern United States. The clinical and pathologic findings associated with this emergent CDV strain have not been reported previously in wolves, to our knowledge. Canine parvovirus 2 (CPV-2b) was also detected in the spleen by IHC and confirmed by conventional PCR as a wild-type strain. The exact impact of CPV-2b on the clinical course is unknown. Early vaccination in this case may have predisposed this Artic wolf to developing clinical disease.

Alzheimer disease has been well associated with mitochondrial dysfunctions. Numerous studies have reported changes in the activity of oxidative phosphorylation (OXPHOS) complexes and mitochondrial dynamics. Recently, dynamin-related protein 1 (Drp-1) has been conceived as a potential therapeutic target as well. We have examined the effect of prolonged treatment of Trans-ferulic acid on streptozocin-induced sporadic dementia of Alzheimer's type. We have found the Ferulic Acid (FA,100 mg/kg) can rescue memory and learning problems and also show significant antioxidant effect while preserving morphology of pyramidal cell layer in hippocampi. Furthermore, FA treatment has shown mitigation in intracerebral-ventricular streptozocin (ICV-STZ) induced bioenergetics loss and dynamic changes by regulating peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha) protein levels in nucleus and hence, mitigating exacerbation of Drp-1 dependent mitochondrial fission and apoptosis by alleviating loss of mitochondrial membrane potential (ΔΨm), downregulating cytochrome-c release into the cytosol by limiting mitochondrial permeability transition pore (mPTP) opening concomitant increase in caspase3 activation, BAX expression and DNA fragmentation along with downregulating glial fibrillary acidic protein (GFAP) expression. FA also restored protein expression of mitofusin2 (Mfn2) a core component of mitochondrial fusion, necessary for mitophagy. We conclude that FA acid may have the propensity to mitigate mitochondrial dysfunction in Alzheimer's disease on prolonging dietary supplementation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Three fishers ( Martes pennanti ), 2 gray foxes ( Urocyon cinereoargenteus ), 1 mink ( Neovison vison ), 1 skunk ( Mephitis mephitis ), and 1 raccoon ( Procyon lotor ), from Vermont and New Hampshire, had lesions on autopsy consistent with canine distemper virus (CDV) infections diagnosed in a 12-mo period in 2016-2017. Lesions of CDV infection were most commonly noted in the lungs (8 of 8 animals), urothelium (5 of 8), biliary tract (5 of 8), gastrointestinal tract (4 of 7), and brain (4 of 6). Splenic lesions were seen in 3 animals. The diagnosis was confirmed via immunohistochemistry and virus isolation. Viral genotyping indicated that all 8 animals were infected with a distinct clade of CDV that has only been reported in wildlife in New England, and this clade of viruses is distinct from vaccine strains. During the 12 mo when these cases occurred, no other CDV clade was identified in any other wildlife or domesticated animal submitted from the 2 states.

Red pandas ( Ailurus fulgens ) are susceptible to canine distemper, with a number of reported vaccine-induced canine distemper cases. Canarypox-vectored recombinant canine distemper vaccines (PureVax Ferret Distemper [PFD] and Recombitek CDV [rCDV]) provide protection without inoculating a live distemper virus, but there are currently no published data regarding these vaccines' safety and efficacy in red pandas. One hundred twenty-two serum samples were collected from 50 captive red pandas and analyzed for antibodies to canine distemper. All naïve red pandas ( n = 20) had negative titers. Naïve pandas receiving two PFD vaccinations had either negative or intermediate titers ( n = 4). In contrast, naïve pandas receiving a series of two or three rCDV vaccinations ( n = 14) had greater antibody responses. Red pandas vaccinated with PFD >12 mo since their last vaccination and a rCDV booster vaccination showed the highest titers observed. We recommend red pandas be administered a series of at least three recombinant vaccine (PDF or rDCV) vaccinations, followed by annual booster vaccinations., (Copyright 2019 by American Association of Zoo Veterinarians.)

Background: The introduction of rotavirus vaccines into national immunization programs necessitates vaccine effectiveness evaluations. Parental report of vaccination status is a simple and accessible source of information; however, its validity is unclear., Aims: To validate parental reports of rotavirus immunization compared to documentation of vaccination in national immunization registry, and to assess vaccine effectiveness by each method., Methods: Parents of 1272 children aged 2-59 months from northern Israel hospitalized for gastroenteritis in 2011-2015 were interviewed on the sociodemographics and rotavirus vaccination status of their child. Rotavirus immunization status based on parental report was compared to that documented in the national immunization registry, which was considered the gold standard. Stool samples collected from patients were tested for rotavirus antigen by immunochromotgraphy. In a rotavirus test-negative case-control study, vaccination history was compared between children found positive for rotavirus and those who tested negative. Vaccine effectiveness for ≥ 1 dose vs. zero doses was calculated as: (1-adjusted odds ratio) * 100., Results: The sensitivity and specificity of parental report of their child's immunization with a rotavirus vaccine were 97% (95% CI 96-98), and 75% (95% CI 65-82), respectively. Kappa coefficient was 0.69 (p < 0.001) for the agreement between the two methods. Rotavirus vaccine effectiveness was 72% (95% CI 54-84) when using parental report of rotavirus immunization and 79% (95% CI 62-88) when using the registry., Conclusion: Parental report of their child's immunization with a rotavirus vaccine demonstrated high sensitivity, although the specificity was relatively low. Vaccine effectiveness was similar regardless of method used to determine rotavirus immunization status. Parental report of vaccination status can be useful in vaccine effectiveness assessment., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: West Nile Virus (WNV) is mosquito-borne virus that is endemic in Israel. In 2015, national disease surveillance demonstrated a sharp increase in disease cases, with 149 cases diagnosed., Methods: Clinical data was extracted from the patients' medical files and laboratory analysis on blood, cerebrospinal fluid or urine was carried out. Data on climate was extracted from the Israel Meteorological Service., Results: Neuroinvasive disease was reported in 70% of cases and case-fatality rate was 16%. Simultaneously with the outbreak, an intense heat wave and an upsurge in summer temperatures occurred., Conclusions: Clinical data shows substantial morbidity and mortality of WNV disease in Israel. Climatic measures are consistent with previous reports and point to the importance of temperature monitoring and rapid implementation of preventive environmental measures during the summer to reduce potential mosquito breeding sites. WNV disease should be suspected as a cause of fever or neurologic disease in travelers returning from endemic countries., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: It is evaluated that a few million individuals worldwide are experiencing Arsenic (As) harmfulness coming about because of anthropogenic discharges. There is likewise proof to propose that As can affect the peripheral, as well as, the central nervous system (CNS). On the contrary, thymoquinone (TQ), a biologically active ingredient of Nigella sativa has exhibited numerous neuro-pharmacological traits since ancient times., Hypothesis/purpose: In the present study, the neuroprotective efficacy of TQ was explored by primarily studying its antioxidant and anti-apoptotic potential against Arsenic trioxide (As 2 O 3 ) induced toxicity in SH-SY5Y human neuroblastoma cell lines., Study Design: For experimentation, cells were seeded in 96 well tissue culture plates and kept undisturbed for 24 h to attain proper adhesion. After 75-80% confluence, cells were pretreated with 10 µM and 20 µM thymoquinone (TQ) for 1 h After adding 2 µM As, cells were set aside for incubation for 24 h without changing the medium., Methods: The mitigatory effects of TQ with particular reference to cell viability and cytotoxicity, the generation of reactive oxygen species, DNA damage, and mitochondrial dynamics were studied., Results: Pretreatment of SH-SY5Y cells with TQ (10 and 20 μM) for an hour and subsequent exposure to 2 μM As 2 O 3 protected the SH-SY5Y cells against the neuro-damaging effects of the latter. Also, the SH-SY5Y cells were better preserved with increased viability, repaired DNA, less free radical generation and balanced transmembrane potential than those exposed to As 2 O 3 alone. TQ pretreatment also inhibited As 2 O 3 -induced exacerbation in protein levels of BAX and PARP-1 and restored the loss of Bcl 2 levels., Conclusion: The findings of this study suggest that TQ may prevent neurotoxicity and As 2 O 3 -induced apoptosis and cytotoxicity. It is, therefore, worth studying further for its potential to reduce the risks of arsenic-related neurological implications., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Background: The epidemiology of human brucellosis (HB) continues to evolve., Objectives: To describe the current epidemiology of HB in Israel in general and in the population at risk., Methods: We calculated the incidence of HB in Israel for the period 2009-2015, overall and for the Arab population. Data are based on mandatory reporting of HB in Israel, defined clinically with either laboratory confirmation or epidemiological linkage to a laboratory-confirmed case. We mapped the geographic distribution of HB throughout the study period according to localities. We specified localities with high incidence (≥ 10 per 100,000 population) and mapped the distribution of dense localities with time., Results: The incidence of HB in the general population in Israel increased sharply from 1.9 per 100,000 in 2009 to a peak of 7.3 per 100,000 in 2014. Each year, 95-100% of cases occurred among Arabs, thus the incidence in the Arab population increased from 10 per 100,000 in 2009 to 33.5 per 100,000 in 2014. Throughout this period 133 different localities reported at least one case of HB, and of these 20 were high-incidence localities during one year at least. During the period 2009-2013 the number of affected localities ranged from 35 to 44 per year and the disease was local, while in 2014 there were 82 localities distributed across the country., Conclusions: We demonstrate the importance of analyzing incidence in the population at risk for a disease. HB is an urgent public health issue in the Arab population in Israel, mandating an immediate and long-term eradication and control program.

As at 12 November 2018, an outbreak of West Nile virus (WNV) was responsible for 139 WNV infection cases in Israel. Here, we characterise the epidemiology of the outbreak and demonstrate that only WNV lineage I was circulating in mosquitoes and responsible for WNV infection in humans. This suggests that the concurrence of the outbreak in Israel with WNV outbreaks in several European countries is not due to a common, more virulent WNV genotype.

Background: Immunization has a significant impact in protecting from severe diseases. Various factors that could influence child immunization coverage and parents' decisions about vaccinating their children should be further explored in specific population groups., Objectives: The current study has two main objectives: to assess the main information sources that affect parental decisions to vaccinate their children and to measure the extent to which these factors differ demographically by exploring the opinions and attitudes within four main population groups in Israel: ultra-Orthodox Jews, all other Jews, non-Bedouin Arabs, and Bedouins., Methods: 1504 parents, with similar representation among four main population groups, participated in this study. A structured, anonymous, self-administered questionnaire was used., Results: The most influential source on parents' decisions to vaccinate their children was the nurse at Mother and Child Health Clinics (MCHCs). Positive attitudes were shown regarding the key role of immunization in preventing severe diseases, while the most important concern expressed was the potential pain to the child while being vaccinated (rather than the safety of the vaccine). Higher compliance rates were reported among participants with a non-academic education level (χ 2  = 12.21, p <0.001), an average level of income (χ 2  = 26.66, p <0.001), and a greater level of religiosity (χ 2  = 5.13, p <0.01). Multivariate analysis showed that higher reliance on Ministry of Health publications (OR = 2.24, 95% CI = 1.49-3.35) and a belief that vaccinations prevent severe diseases (OR = 1.55, 95% CI = 1.06-2.25) predicted higher vaccination compliance. A concern about unsafe components of the vaccinations predicted lower compliance (OR = 0.41, 95% CI = 0.25-0.66). Bedouins demonstrated the highest compliance rate (99%), were most influenced by all information sources, and demonstrated the most pro-vaccination positions., Conclusions: The factor that most influenced Israeli parents' decisions to vaccinate their children was their degree of trust in information sources about vaccinations, particularly the nurses at the MCHCs., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

We report preliminary findings of a large outbreak of human leptospirosis with 36 confirmed/probable and 583 suspected cases from June-August 2018, linked to contaminated water bodies in Northern Israel. There was a travel-associated case in Germany; additional cases are being investigated in other countries. The presumed chain of transmission, implicating wild boar and cattle, raises multiple challenges for risk assessment, risk management and risk communication currently being addressed by a public health response team.

Background: Canine distemper (CD) is a highly contagious, systemic, viral disease of dogs seen worldwide. Despite intensive vaccination in developed countries, recent reports suggest both the re-emergence and increased activity of Canine distemper virus (CDV) worldwide, including the United States. CDV is an RNA virus of the genus Morbillivirus within the family Paramyxoviridae. Viral genomic RNA encodes six structural proteins. Of the six structural proteins, the hemagglutinin (H) gene has the greatest genetic variation and is therefore a suitable target for molecular epidemiological studies. The majority of neutralizing epitopes are found on the H protein, making this gene also important for evaluation of changes over time that may result in antigenic differences among strains. The aim of this study was to determine the phylogenetic relationship of CDV strains circulating in the US., Methods: Fifty-nine positive canine distemper virus samples collected from dogs from different regions and states from 2014 to 2017 were sequenced with a targeted next-generation sequencing (NGS) method. The sequences of the H, F, and P genes and the matrix-fusion (M-F) intergenic region of the amplified CDVs were analyzed individually., Results: Sequence analysis of the H gene revealed that there are at least 3 different lineages of CDV currently circulating in the US. These lineages include America-3 (Edomex), America-4, and a clade that was previously reported in association with an outbreak in Wyoming, which was linked to a domestic dog-breeding facility in Kansas in 2010. These lineages differ from the historically identified lineages in the US, including America-1, which contains the majority of the vaccine strains. Genetic differences may result in significant changes to the neutralizing epitopes that consequently may lead to vaccine failure. Phylogenetic analyses of the nucleotide sequences obtained in this study of the F and P genes and the M-F intergenic region with sequences from the GenBank database produced similar findings to the H gene analysis., Conclusions: The CDV lineages currently circulating in the US differ from the historically identified lineages America-1. Continuous surveillance is required for monitoring circulating CDV strains in the US, to prevent potential vaccine breakthrough events.

Preclinical Research & Development Parkinson's disease (PD) is the second most common neurodegenerative disorder that affects approximately 10 million people worldwide. The risk of developing PD and similar neurodegenerative disorders increases with age and an estimated 4% people are diagnosed with the disease before reaching the age of 50. Oxidative stress, cytotoxicity, and mitochondrial dysfunction are common features exhibited in the development of PD. The 6-hyroxydopamine (6-OHDA) model of PD is one of the most well characterized and studied models of the disease. 6-OHDA, a neurotoxin, can induce most characteristic features of the disease, including mitochondrial dysfunction in-vivo and in-vitro. SH-SY5Y is a neuroblastoma cell line of human origin that has been used for dose response studies on PD in the past. Based on previous data, we have used SH-SY5Y cells as an in-vitro model of PD to analyse the phytomedicinal potential of perillyl alcohol (PA), a monoterpenoid obtained from essential oils of various plants such as sage, peppermint and lavender. We have found that pretreatment with PA (10 μM and 20 μM) mitigated 6-OHDA (150 μM) induced cytotoxicity in a dose-dependent manner. We observed marked restoration of cell viability and mitochondrial membrane potential (MMP) as well as reduced reactive oxygen species generation, Cytochrome c immunofluorescence and DNA fragmentation after treatment with PA. On the basis of on our data, we have come to the conclusion that PA demonstrates sufficient neuroprotective activity to provide new avenues in therapy of PD and its apparent target being restoration of MMP can lead to better understanding of the disease., (© 2018 Wiley Periodicals, Inc.)

Pertussis is the only vaccine-preventable disease that has re-emerged in Israel. In the last two decades, despite high primary immunization coverage, crude incidence increased over tenfold, with especially high morbidity among infants and adolescents and with 19 infant deaths. Two pertussis vaccine boosters were added, in 2005 for 7-year-olds and in 2011 for 13-year-olds. We reviewed age group incidence from 1999 to 2016, before and after the booster program introduction. We compared three groups of 13-15 year-olds with identical primary immunization but different booster immunization histories. Vaccine effectiveness was calculated before and after adjustment for specific incidence in those aged 65 and over. Two years after one booster, adjusted vaccine effectiveness was 74.5%. Two years after two boosters, adjusted vaccine effectiveness was 91.8%. However, crude morbidity rates were not reduced. The booster program has been effective only among recipient groups. The program will be continued. Israel is now encouraging pregnant women to be vaccinated against pertussis to improve protection of infants.

The laboratory diagnosis of infectious diseases, especially those caused by mixed infections, is challenging. Routinely, it requires submission of multiple samples to separate laboratories. Advances in next-generation sequencing (NGS) have provided the opportunity for development of a comprehensive method to identify infectious agents. This study describes the use of target-specific primers for PCR-mediated amplification with the NGS technology in which pathogen genomic regions of interest are enriched and selectively sequenced from clinical samples. In the study, 198 primers were designed to target 43 common bovine and small-ruminant bacterial, fungal, viral, and parasitic pathogens, and a bioinformatics tool was specifically constructed for the detection of targeted pathogens. The primers were confirmed to detect the intended pathogens by testing reference strains and isolates. The method was then validated using 60 clinical samples (including tissues, feces, and milk) that were also tested with other routine diagnostic techniques. The detection limits of the targeted NGS method were evaluated using 10 representative pathogens that were also tested by quantitative PCR (qPCR), and the NGS method was able to detect the organisms from samples with qPCR threshold cycle ( C T ) values in the 30s. The method was successful for the detection of multiple pathogens in the clinical samples, including some additional pathogens missed by the routine techniques because the specific tests needed for the particular organisms were not performed. The results demonstrate the feasibility of the approach and indicate that it is possible to incorporate NGS as a diagnostic tool in a cost-effective manner into a veterinary diagnostic laboratory., (Copyright © 2018 Anis et al.)

Introduction: The 2013 reemergence of wild poliovirus in Israel led to the reinstatement of a routine OPV vaccination. Fearing VAPP in immunocompromised, the MOH regulated contraindications for vaccination candidates and household contacts. In this study we estimate the size of the contraindicated population to OPV vaccination., Method: We studied vaccination candidates aged 2-9 and 14-23 months and probable household contacts. Using the rate of contraindications extracted for each study group from a medical records database, a statistical model was built to estimate the probability of contraindications in candidates., Results: 3.9% of the 2-9-month-old study group and 4% of the 14-23-month-old group had contraindications by either self or household contacts., Conclusion: A statistical model can provide an estimation of the contraindicated population and can be used in the future when devising vaccination campaigns. In contrast to concerns raised by the MOH, our findings show a smaller than anticipated contraindicated population., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Canine distemper virus (CDV) is an RNA virus of the genus Morbillivirus within the family Paramyxoviridae. CDV produces multi-systemic disease in dogs and other terrestrial carnivores. With the development of modified live vaccines in the 1950s and 1960s, the disease, with a few exceptions, has been successfully controlled. However, recently the cases of CDV in vaccinated dogs have been increasing throughout the world, including the United States. There are many reasons that can lead to vaccine failure, including antigenic differences between the vaccine strains and the currently circulating wild-type strains. Currently, there are at least three genetically different CDV lineages circulating in the US. Therefore, in this study, we evaluated various wild-type CDV and vaccine isolates to determine if the genetic differences observed among various strains result in significant antigenic differences based on changes to the neutralizing epitopes. The results of a cross-neutralization assay revealed that there are antigenic differences among the tested CDV wild-type isolates as well as between the tested isolates and the vaccine strains currently used in the US. Therefore, these results suggest the need to develop an updated CDV vaccine., (Copyright © 2018 Elsevier B.V. All rights reserved.)

To investigate the association between the incidence of human brucellosis (HB) and adverse pregnancy outcomes (APOs), a population-based, cross-sectional aggregate data study was conducted in Israel between 2010 and 2014. HB-endemic localities were matched by ethnicity, population size and socioeconomic status to localities with a low incidence of HB. We compared APO rates in high-incidence vs low-incidence localities. The primary outcome was intrauterine fetal demise (IUFD). Secondary outcomes were premature birth (less than 37 weeks), early or threatened labour and poor fetal growth. APOs are expressed as events per 1,000 live or dead births. Eleven high-incidence localities, all Arab villages or cities, were matched to 11 low-incidence localities. Localities were well-matched with regard to the matching criteria, fertility indices, health insurance access and education, but were imbalanced geographically. All defined APOs occurred significantly more frequently in the high-incidence localities. The associations translated to an absolute increase of 3.6 cases of IUFD (95% CI 1.6-5.3), 11.7 preterm births (4.8-18.3), 6.6 cases of early or threatened labour (2.2-10.9) and 7 cases of poor fetal growth (3-10.8), per 10,000 live or dead births. Owing to a geographic imbalance between high- and low-incidence localities, we conducted an analysis restricted to Southern localities of Arab Bedouins showing a significant association between yearly HB incidence and IUFD incidence, odds ratio 1.05 (1.03-1.06). HB incidence is epidemiologically linked to serious pregnancy complications. Early detection of infection through active surveillance during pregnancy followed by appropriate treatment should be evaluated as additional public heath strategy in endemic settings.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common type of dementia in elderly ( >65years of age). Excessive extra cellular deposits of amyloid beta (Aβ) are a pathological feature of AD. Aβ can cause cell death through oxidative damage; recent studies have implicated opening of mPTP as a detrimental event in AD-related mitochondrial dysfunctions. Over the past few years, natural compounds with antioxidant properties have shown promise for intervention in AD., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives Feline leukaemia virus (FeLV), a gamma retrovirus, causes diseases of the feline haematopoietic system that are invariably fatal. Rapid and accurate testing at the point-of-need (PON) supports prevention of virus spread and management of clinical disease. This study evaluated the performance of an insulated isothermal PCR (iiPCR) that detects proviral DNA, and a reverse transcription (RT)-iiPCR that detects both viral RNA and proviral DNA, for FeLV detection at the PON. Methods Mycoplasma haemofelis, feline coronavirus, feline herpesvirus, feline calicivirus and feline immunodeficiency virus were used to test analytical specificity. In vitro transcribed RNA, artificial plasmid, FeLV strain American Type Culture Collection VR-719 and a clinical FeLV isolate were used in the analytical sensitivity assays. A retrospective study including 116 clinical plasma and serum samples that had been tested with virus isolation, real-time PCR and ELISA, and a prospective study including 150 clinical plasma and serum samples were implemented to evaluate the clinical performances of the iiPCR-based methods for FeLV detection. Results Ninety-five percent assay limit of detection was calculated to be 16 RNA and five DNA copies for the RT-iiPCR, and six DNA copies for the iiPCR. Both reactions had analytical sensitivity comparable to a reference real-time PCR (qPCR) and did not detect five non-target feline pathogens. The clinical performance of the RT-iiPCR and iiPCR had 98.82% agreement (kappa[κ] = 0.97) and 100% agreement (κ = 1.0), respectively, with the qPCR (n = 85). The agreement between an automatic nucleic extraction/RT-iiPCR system and virus isolation to detect FeLV in plasma or serum was 95.69% (κ = 0.95) and 98.67% (κ = 0.85) in a retrospective (n = 116) and a prospective (n = 150) study, respectively. Conclusions and relevance These results suggested that both RT-iiPCR and iiPCR assays can serve as reliable tools for PON FeLV detection.

Arsenic, being a global pollutant needs a potential remedy which could fight against its associated toxicities. Ellagic acid (EA) is a known agent for its anti-inflammatory, antioxidant and antiapoptotic effects, and it is commonly found in fruits. The present study is designed to determine protective efficacy of EA against arsenic induced toxicity with special mention to inflammation and mitochondrial dysfunction in hippocampi of wistar rats. Rats were pre-treated with EA (20 and 40 mg/kg b.wt; p.o. for 11 days) along with arsenic (10 mg/kg; p.o. for 8 days). Total reactive oxygen species level and mitochondrial membrane potential were analyzed using flow cytometry. Protein and mRNA expression of apoptotic and inflammatory markers were also evaluated in rat hippocampus. Our results show that arsenic exposure increased total ROS generation and DNA fragmentation, decreased mitochondrial membrane potential alongwith an increase in expression of pro-apoptotic and inflammatory markers. suggesting that EA complementation downregulated total ROS generation dose dependently. Apoptotic markers, BAX and Bcl 2 as well as inflammatory markers, IL-1β, TNFα, INFγ got altered significantly on its administration. Moreover, it also attenuated effects on mitochondrial membrane potential. Based on our findings, EA might substantiate to be a budding therapeutic candidate against arsenic induced neurotoxicity.

In the current study, neuroprotective significance of ellagic acid (EA, a polyohenol) was explored by primarily studying its antioxidant and antiapoptotic potential against arsenic trioxide (As 2 O 3 )-induced toxicity in SH-SY5Y human neuroblastoma cell lines. The mitigatory effects of EA with particular reference to cell viability and cytotoxicity, the generation of reactive oxygen species, DNA damage, and mitochondrial dynamics were studied. Pretreatment of SH-SY5Y cells with EA (10 and 20 μM) for 60 min followed by exposure to 2 μM As 2 O 3 protected the SH-SY5Y cells against the harmful effects of the second. Also, EA pre-treated groups expressed improved viability, repaired DNA, reduced free radical generation, and maintained altered mitochondrial membrane potential than those exposed to As 2 O 3 alone. EA supplementation also inhibited As 2 O 3 -induced cytochrome c expression that is an important hallmark for determining mitochondrial dynamics. Thus, the current investigations are more convinced for EA as a promising candidate in modulating As 2 O 3 -induced mitochondria-mediated neuronal toxicity under in vitro system., (© 2018 Wiley Periodicals, Inc.)

Canine distemper virus (CDV) affects many wild and captive, nondomestic species worldwide but has not been previously reported in Xenarthra. Paucity of information on vaccination safety and efficacy presents challenges for disease prevention in captive collections. CDV infections and subsequent mortalities in five captive Linnaeus's two-toed sloths ( Choloepus didactylus) in eastern Tennessee are reported. Clinical signs included oculonasal discharge, oral ulcerations, and diarrhea, and the diagnosis was confirmed by necropsy, histopathology, immunohistochemistry, virus isolation, and polymerase chain reaction. Viral sequencing identified the strain to be consistent with a new CDV lineage currently affecting domestic dogs and wildlife in Tennessee. Seven sloths were examined and vaccinated using a recombinant CDV vaccine on days 0 and 21. Subsequent blood samples showed increased titers in 3/4 sloths. Based on the outbreak and serologic findings postvaccination without adverse effects, the authors recommend recombinant CDV vaccination in sloths exposed to known carriers of CDV.

Objectives: Israel has a long history of West Nile virus (WNV) morbidity, and the rate of detection of WNV in mosquitoes has been high since 2000. The aim of this study was to integrate several WNV datasets in order to gain an insight into the geographical distribution of WNV in Israel., Methods: Three choropleth maps were generated showing WNV human morbidity, WNV prevalence in mosquitoes, and the results of a nationwide serological survey, based on the division of Israel into 15 sub-districts., Results: The maps show a high endemicity of WNV in Israel. In respect to the morbidity map, the population residing in the central part of the country and in Arava Region is at higher risk of developing the disease than the population of the rest of Israel. Interestingly, high prevalence rates of both WNV serology and WNV-infected mosquitoes were detected in Arava Region, but lower prevalence rates were detected in most areas of the coastal region, suggesting that other factors might also be important in the development of symptomatic WNV infections., Conclusions: These results underline the high prevalence of WNV in Israel and point to specific risk areas for WNV infections across the country., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Listeriosis is a disease of humans and domestic mammals (mainly ruminants) with variable manifestations, primarily encephalitis, septicemia, and abortion. Although Listeria monocytogenes readily causes illness in ruminants, the prevalence among domestic South American camelids (llamas and alpacas) is low and has not been documented in their wild counterparts, the vicuna and guanaco. We describe herein the clinical signs, autopsy findings, and histopathology of septicemia and suppurative meningoencephalitis caused by L. monocytogenes in 2 neonatal llamas ( Llama glama) from the same herd. L. monocytogenes was isolated in pure culture and identified by real-time PCR on fresh and paraffin-embedded tissue samples of the brain from both crias. This presentation of septicemic listeriosis with meningoencephalitis in 2 animals from the same group is unusual, especially among llamas.

In Israel, 262 mumps cases were registered between 1 January and 28 August 2017 despite a vaccine coverage of ≥ 96%. The majority (56.5%) of cases were adolescents and young adults between 10 and 24 years of age. Nearly twice as many cases were reported in males than in females. Sequence information identified genotype G and suggested specific transmission chains in different religious communities, with the Muslim population in Jerusalem being most severely affected., (This article is copyright of The Authors, 2017.)

Between December 2016 and June 2017, 19 Hepatitis A virus (HAV)-positive cases, 17 of which were among men who have sex with men (MSM) were identified in the Tel Aviv area. Seven of the 15 sewage samples collected between January and June 2017 were also HAV-positive. All sequences clustered with two of the three strains identified in the current European HAV outbreak. We demonstrate that despite an efficient vaccination programme, HAV can still be transmitted to an unvaccinated high-risk population., (This article is copyright of The Authors, 2017.)

Background: There is on ongoing debate in the literature regarding the real burden of STIs (sexually transmitted infections) in Western countries and the proper strategies needed to estimate and to prevent them. Our purpose is to present an evidence-based national strategic plan for STI prevention in Israel through assessing the current burden of illness, leading international preventive strategies, and practical policymaking experience., Methods: Epidemiologic and health policy data on STIs were analyzed from various sources: a) systematic national surveillance data for the years 2002-2014; b) the international scientific literature (published between 2002-16; keywords: Sexually Transmitted Diseases (STD) (or STI) AND prevention AND intervention AND gonorrhea OR chlamydia OR syphilis; c) internal Ministry of Health (MOH) analyses and reports, and d) expert opinion., Results: Incidence rates in Israel of Chlamydia trachomatis (chlamydia), Neisseria gonorrhea (gonorrhea) and Treponema pallidum (syphilis) are lower than in most Western countries. However, rates vary among population subgroups: chlamydia, gonorrhea and syphilis are higher in Jews than in non-Jews, and this gap has increased for chlamydia over the past decade. Primary and secondary syphilis rates have increased among men having sex with men (MSM). It is likely that STIs are under-reported and that incidence is even rising due to migration. A key recommendation is the establishment of an active surveillance system of STIs, utilizing active case finding in high risk populations, along with regular contact with STI clinics run by the four national health management organizations and by the MoH. As with most European countries, the low prevalence of chlamydia and gonorrhea does not justify population-wide screening. Conversely, the increasing incidence of syphilis among MSM should lead to regular screening among this group., Conclusions: A national STIs prevention strategy for the year 2025 was presented. Although the current burden of illness is low relatively to other Western countries, this is thought to reflect a certain degree of underreporting. These and other gaps suggest a need for focused epidemiologic and health services research to better characterize health risk behaviors as well as provider practice patterns. Innovative implementation strategies have been described, together with the capacity building components needed for developing specific and implementable policy recommendations for the year 2025.

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.

Canine distemper virus (CDV) is a common cause of a multisystemic disease in both domestic dogs and wildlife species, including raccoons and foxes. Outbreaks of CDV in domestic dogs in eastern Tennessee have occurred since 2012, and it was determined that these outbreaks resulted from a novel genotype of CDV. We hypothesized that this virus is also infecting area wildlife and may be a source of the virus for these outbreaks in dogs. From 2013 to 2014, autopsies were performed and tissues collected from raccoons (Procyon lotor; n = 50) and gray foxes (Urocyon cinereoargenteus; n = 8) for CDV testing. A real-time reverse transcription PCR was used to document the presence of CDV in tissue samples, and a portion of the virus was subsequently sequenced for phylogenetic analysis. A high percentage of wildlife, both with (86%) and without (55%) clinical signs, tested positive for CDV, with the majority (77%) testing positive for the novel genotype. Microscopic findings, including syncytia in the lungs and viral inclusion bodies in urothelium, astrocytes, neurons, and bronchiolar epithelium, were also consistent with canine distemper. Minimal inflammation in the central nervous system of affected animals was indicative of the acute neurologic form of the disease. Pneumonia and parasitism were also commonly found in CDV-infected animals. Based on these results, CDV appears to be prevalent in eastern Tennessee wildlife. Subclinical or clinically recovered shedders are a potential source of this novel genotype for domestic dogs, and this genotype is genetically distinct from vaccine strains., (© 2016 The Author(s).)

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., (Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Heavy metals can significantly bioaccumulate in fish tissues. The step wise mechanism of heavy metal toxicities on fish health is still limited. The present study assessed the tissue-specific antioxidant response and oxidative stress biomarkers of commercially important fish species namely, Channa striatus and Heteropneustes fossilis inhabiting Kali River of northern India where heavy-metal load is beyond the World Health Organisation - maximum permissible limits. Heavy metals chromium (Cr), nickel (Ni), lead (Pb) and cadmium (Cd) were elevated in both fish species compared to recommended values of the Federal Environmental Protection Agency (FEPA), 1999 for edible fishes. Reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CATA) activities in all tissues (brachial, neural, renal and hepatic) were altered. Cellular lipid and protein compromisation in both fishes induced by heavy metals was determined by lipid peroxidation (LPO) and protein carbonylation (PC) assays. Micronucleus (MN) test of erythrocytes and comet assay of liver cells confirmed genotoxicity. Histopathology of the liver, kidney and brain of affected fishes was distorted significantly with its reference fishes thereby affecting the quality and quantity of these fish stocks. This raises a serious concern as these fishes are consumed by the local population which would ultimately affect human health., (Copyright © 2015. Published by Elsevier Inc.)

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., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: After 25 years without poliomyelitis cases caused by circulating wild poliovirus (WPV) in Israel, sewage sampling detected WPV type 1 (WPV1) in April 2013, despite high vaccination coverage with only inactivated poliovirus vaccine (IPV) since 2005., Methods: We used a differential equation-based model to simulate the dynamics of poliovirus transmission and population immunity in Israel due to past exposure to WPV and use of oral poliovirus vaccine (OPV) in addition to IPV. We explored the influences of various immunization options to stop imported WPV1 circulation in Israel., Results: We successfully modeled the potential for WPVs to circulate without detected cases in Israel. Maintaining a sequential IPV/OPV schedule instead of switching to an IPV-only schedule in 2005 would have kept population immunity high enough in Israel to prevent WPV1 circulation. The Israeli response to WPV1 detection prevented paralytic cases; a more rapid response might have interrupted transmission more quickly., Conclusions: IPV-based protection alone might not provide sufficient population immunity to prevent poliovirus transmission after an importation. As countries transition to IPV in immunization schedules, they may need to actively manage population immunity and consider continued use of OPV, to avoid the potential circulation of imported live polioviruses before globally coordinated cessation of OPV use., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)