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OBJECTIVE: Genital neonatal herpes simplex virus type 1 (HSV-1) infection was observed in a series of neonates after traditional Jewish ritual circumcision. The objective of this study was to describe neonate genital HSV-1 infection after ritual circumcision and investigate the association between genital HSV-1 after circumcision and the practice of the traditional circumcision. METHODS: Eight neonates with genital HSV-1 infection after ritual circumcision were identified. RESULTS: The average interval from circumcision to clinical manifestations was 7.25 +/- 2.5 days. In all cases, the traditional circumciser (the mohel) had performed the ancient custom of orally suctioning the blood after cutting the foreskin (oral metzitzah), which is currently practiced by only a minority of mohels. Six infants received intravenous acyclovir therapy. Four infants had recurrent episodes of genital HSV infection, and 1 developed HSV encephalitis with neurologic sequelae. All four mohels tested for HSV antibodies were seropositive. CONCLUSION: Ritual Jewish circumcision that includes metzitzah with direct oral-genital contact carries a serious risk for transmission of HSV from mohels to neonates, which can be complicated by protracted or severe infection. Oral metzitzah after ritual circumcision may be hazardous to the neonate. [ABSTRACT FROM AUTHOR]

Objectives: This survey was conducted to describe current European postnatal prophylaxis (PNP) and infant feeding policies with the aim of informing future harmonized guidelines., Methods: A total of 32 senior clinicians with relevant expertise, working in 20 countries within the European Region, were invited to complete a REDCap questionnaire between July and September 2023., Results: Twenty-three of the 32 invited paediatricians responded, representing 16/20 countries. There were multiple respondents from the same country for Italy (n = 5), the UK (n = 2), Germany (n = 2) and France (n = 2). All countries use risk stratification to guide PNP regimen selection. Nine out of 16 countries reported three risk categories, six out of 16 reported two, and one country reported differences in categorization. Criteria used to stratify risk varied between and within countries. For the lowest risk category, the PNP regimen reported ranged from no PNP to up to four weeks of one drug; the drug of choice reported was zidovudine, apart from one country which reported nevirapine. For the highest risk category, the most common regimen was zidovudine/lamivudine/nevirapine (20/23 respondents); regimen duration varied from two to six weeks with variation in recommended dosing. Guidelines support breastfeeding for infants born to people living with HIV in eight out of 16 countries; in the other eight, guidelines do not support/specify., Conclusions: Guidelines and practice for PNP and infant feeding vary substantially across Europe and within some countries, reflecting the lack of robust evidence. Effort is needed to align policies and practice to reflect up-to-date knowledge to ensure the vertical transmission risk is minimized and unnecessary infant HIV testing and PNP avoided, while simultaneously supporting families to make informed decisions on infant feeding choice., (© 2024 The Author(s). HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Abstract: Neutrophils are the first line of defense against invading pathogens. Neutrophils execute and modulate immune responses by generating reactive oxygen species (ROS). Chronic granulomatous disease (CGD) is a primary immune deficiency disorder of phagocytes, caused by inherited mutations in the genes of the nicotinamide adenine dinucleotide phosphate reduced oxidase enzyme. These mutations lead to failure of ROS generation followed by recurrent bacterial and fungal infections, frequently associated with hyperinflammatory manifestations. We report a multicenter cumulative experience in diagnosing and treating patients with CGD. From 1986 to 2021, 2918 patients experiencing frequent infections were referred for neutrophil evaluation. Among them, 110 patients were diagnosed with CGD: 56 of Jewish ancestry, 48 of Arabic ancestry, and 6 of non-Jewish/non-Arabic ancestry. As opposed to other Western countries, the autosomal recessive (AR) CGD subtypes were predominant in Israel (71/110 patients). Thirty-nine patients had X-linked CGD, in most patients associated with severe infections (clinical severity score ≥3) and poor outcomes, presenting at a significantly earlier age than AR-CGD subtypes. The full spectrum of infections and hyperinflammatory manifestations is described. Six patients had hypomorphic mutations with significantly milder phenotype, clinical severity score ≤2, and better outcomes. Hematopoietic stem cell transplantation was implemented in 39 of 110 patients (35.5%). Successful engraftment was achieved in 92%, with 82% long-term survival and 71% full clinical recovery. CGD is a complex disorder requiring a multiprofessional team. Early identification of the genetic mutation is essential for prompt diagnosis, suitable management, and prevention., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Objectives: We describe 10 new cases of otogenic (n = 8) and nonotogenic (n = 2) skull base osteomyelitis (SBO) in previously healthy children and review the literature on SBO in the pediatric population., Methods: We retrospectively analyzed the medical records of 10 children (age range 0.9-12.8 years) discharged with a diagnosis of SBO between 2015 and 2020 in 2 children's hospitals in central Israel., Results: Five patients presented with fever and 5 with otological signs and symptoms. All 10 children underwent a comprehensive clinical evaluation, imaging studies (computerized tomography or magnetic resonance imaging) and laboratory investigations. The physical examination revealed neurologic findings, including nuchal rigidity, papilledema, and apathy, in 4 patients. All 8 otogenic patients underwent surgical intervention and the 2 nonotogenic patients, who were diagnosed as having deep neck and throat infections, responded well to treatment consisting of antibiotics without surgery., Conclusions: Early diagnosis of pediatric SBO can be challenging because the symptoms are often nonspecific. The final diagnosis relies mainly on imaging, preferably magnetic resonance imaging. Surgical intervention is usually mandatory in the otogenic patients, whereas the nonotogenic patients respond well to medical management alone., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Pott's puffy tumor (PPT) is a rare complication of frontal sinusitis. Although it may occur at any age, the incidence is higher during adolescence., Methods: We report a series of 10 pediatric patients (9-17 years of age) who presented with PPT in 2 tertiary care pediatric hospitals in central Israel between January 2018 and August 2022 and review the published literature on pediatric PPT., Results: The most common clinical presentations included headache (10 cases), frontal swelling (6 cases) and fever (5 cases). Symptom duration before admission was between 1 and 28 days (median 10 days). The diagnosis of PPT was made by imaging studies at a median of 1 day after admission. All 10 patients underwent computed tomography studies, and 6 patients also underwent magnetic resonance imaging. The overall rate of intracranial complications was 70%. All 10 children were treated with systemic antibiotics and surgical interventions. Streptococcus constellatus group was the most common causal bacteria. All 10 patients recovered uneventfully., Conclusions: Our findings show that a high index of suspicion for PPT should be applied to adolescents presenting with prolonged headache and frontal swelling. Contrast-enhanced computed tomography is an appropriate first tool for the evaluation; however, an magnetic resonance imaging should be performed to determine the necessity of intracranial interventional treatments if there is any suspicion of intracranial involvement. Complete recovery can be expected with appropriate antibiotic treatment and surgical intervention in most of the cases., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Intensive chemotherapy for acute lymphoblastic leukemia (ALL) may affect the immune system and potentially the immune memory causing antibodies provided by vaccination to disappear. There are disagreements regarding the guidelines for posttreatment immunization strategy., Methods: Ninety-six children (aged 1-18 years at diagnosis) who completed chemotherapy for ALL were recruited. Antibody levels in the patient's serum against measles, varicella, polio, pertussis, hepatitis A, and hepatitis B were tested after completion of chemotherapy in patients who were fully vaccinated against these agents. Children who did not have positive serology to specific agents were revaccinated with a single dose accordingly. Antibody concentrations were measured again at least 4 weeks after revaccination., Results: Positive antibody levels varied between the different agents. The highest percentage of positive serology was against polio (87%) and the lowest against pertussis (4%) (p < .001). There were significant differences between patients with high risk (HR) and non-HR ALL regarding serology status for some vaccines. After revaccination, the levels of response to each booster dose were significantly different: 100% after booster dose for varicella and polio, and only 34% after pertussis booster., Conclusions: Loss of humoral protection for vaccine preventable diseases is a common finding among patients with ALL. Revaccination with one dose of vaccine after completion of chemotherapy achieved seroconversion in 34-100% of the patients depending on the type of vaccine. We recommend this revaccination schedule to all children who completed ALL therapy and were previously fully vaccinated., (© 2023 Wiley Periodicals LLC.)

Objective: Isolation and school closure during the COVID-19 pandemic could decrease human papillomavirus (HPV) vaccination uptake and potentially increase future HPV-related morbidity among unvaccinated populations. The aim of our study was to investigate HPV vaccination rates in Israel during the pandemic., Methods: The HPV vaccination rates were compared before and during the COVID-19 pandemic years (2020-2021). Data regarding HPV vaccination between 2015 and 2021 were extracted from the Israeli Ministry of Health online reports. Vaccination rates were compared with other childhood vaccines, given at similar ages. Israeli HPV vaccination rates were further compared with England and Australia, which have an established vaccination infrastructure., Results: The average Israeli coverage of first-dose HPV vaccine was 60.2%, with significant variations from 2015 to 2021. During the pandemic years, first-dose vaccine coverage increased compared with the 3 previous years. The pandemic had also no apparent influence on other childhood vaccine uptake, even though adolescents in Israel missed many school days during this time. Average vaccine uptake in England and Australia was significantly higher than Israel ( p = .009); however, first-dose vaccination rates decreased considerably in England during 2020, to a nadir of 59%. The pandemic had little effect on HPV vaccination rates in Australia., Conclusions: Despite many school days missed, the COVID-19 pandemic did not result in a decrease in HPV vaccine uptake in Israel. The pandemic could prove a good opportunity to further educate the public regarding the importance of whole-population vaccination programs. Implementing catch-up vaccination programs may bridge "vaccination gaps" that may be caused by future pandemics., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2023, ASCCP.)

Among 46 infants colonized with vancomycin-resistant Enterococcus faecium during an outbreak in a neonatal intensive care unit, the estimated time until half had achieved clearance was 217 days. All 40 infants who completed follow-up cleared carriage by 1 year. No predictors of prolonged carriage (> 6 months) were identified.

Background: The past decade has witnessed a rise in Fusobacterium infections. This study aimed to describe the epidemiology, clinical and demographic characteristics and outcomes associated with Fusobacterium infections in hospitalized children in central Israel., Methods: We retrospectively analyzed the medical records of children <18 years old who had been admitted with a diagnosis of invasive Fusobacterium infection (IFI) between January 2010 and April 2020. Clinical, laboratory and microbiologic data were retrieved. IFI diagnosis was based upon microbiological identification in any specimen by culture or by 16S ribosomal RNA polymerase chain reaction., Results: Fifty-one children (26 boys) with a median age of 3 years (range, 5-16 years) were included. Hospitalizations for IFI increased from 19 of 100,000 admissions between 2010 and 2015 to 50 of 100,000 between 2016 and 2020, representing a 2.5-fold increase. Most of the infections were from an otogenic source (n = 28, 55%) followed by an oropharyngeal/respiratory source (n = 21, 41%). The most common complications were subperiosteal and epidural abscesses (41% and 37%, respectively). Thrombosis was diagnosed in 11 children, 10 of whom had sinus vein thrombosis. All had an otogenic source. Children with otogenic compared with all other infection sources were significantly younger (median age of 1.9 vs. 3 years; P < 0.001). Forty-seven children (92%) underwent a surgical intervention. All patients survived, one with neurologic sequelae., Conclusions: The admissions for IFI in children increased 2.5-fold during the last decade. The most common source is otogenic, especially among younger children, and it is associated with high complication rates. Current management, including combinations of antibiotics and surgical interventions, leads to favorable outcome., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: Minimal data exist regarding the severity of COVID-19 in febrile infants under 60 days old. This multicentre prospective study explored the clinical course and outcomes of this hospitalised patient population, as, to date, the best approach has not been specifically addressed., Methods: This study focused on the clinical features, laboratory parameters and outcomes of febrile infants up to 60 days old who tested positive for the virus and were hospitalised in Israel from March 2020 to January 2021. The data were extracted from a real-time prospective surveillance network for COVID-19 that includes 20 of the country's 26 hospitals., Results: We identified 75 febrile young infants (60% female) with COVID-19 at a median age of 28 days (range 8-56 days). Of these, 84% had an unremarkable medical history, 29% had respiratory symptoms, and 96% had a mild illness. The Rochester criteria showed that 44% were considered at high-risk for serious bacterial infections, and we found that eight infants actually had concomitant bacterial infections. Outcomes were excellent, and no complications or fatalities were reported., Conclusion: The excellent outcomes of young febrile infants with COVID-19 closely resembled other respiratory viral aetiologies of fever in this age group, and there were no fatalities., (©2021 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: Most pediatric coronavirus disease 2019 (COVID-19) is mild. We assessed nationally severe COVID-19, including pediatric inflammatory multisystem syndrome (PIMS), in hospitalized children., Methods: An ongoing, prospective, national surveillance was conducted from March 2020 through March 2021, at 20 hospitals treating children <18 years across Israel (~75% of Israeli hospitals)., Results: Overall, 1007 cases (439 outpatients and 568 hospitalized) identified represent 0.35% of pediatric COVID-19 nationwide (n = 291 628). Of hospitalized cases, 464 (82%), 48 (8%), and 56 (10%) had mild, moderate/severe, and PIMS disease, respectively. The mean ± SD age was 5.6 ± 6.4 years. In mild, moderate/severe, and PIMS disease, 55%, 23%, and 4% of patients were <1 year old, respectively. Obesity was reported in 1%, 4%, and 13% of patients, respectively (P < .001). The most common symptom was fever in 67%, 60%, and 100%, respectively, whereas respiratory symptoms were documented in 33%, 41%, and 38% of patients, respectively. Lymphopenia was recorded in 25%, 60%, and 86% of cases, respectively. PIMS diagnosis was mainly serology-based (in 59%). Gastrointestinal symptoms, cardiovascular involvement, rash, and conjunctivitis were noted in 82%, 61%, 57%, and 34% of PIMS episodes, respectively. Elevated C-reactive protein (100%), ferritin, troponin, D-dimer, low albumin, and thrombocytopenia were common in PIMS. Echocardiography revealed pathological findings in 33% of patients. PIMS mainstay treatment included corticosteroids (77%) and intravenous immunoglobulin (53%). No mortality was recorded., Conclusions: At a national level, pediatric COVID-19 is mild, even in hospitalized cases, with only a third presenting with respiratory involvement. PIMS is rare, but necessitates a high index of suspicion, and with suitable treatment prognosis is favorable., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Group A Streptococcus can cause serious and sometimes life-threatening disease in children. The past few years have witnessed a rise in invasive group A Streptococcus infection (iGASi) for unclear reasons. This study attempted to describe the epidemiology, the clinical and demographic characteristics and the outcomes associated with iGASi in hospitalized children in central Israel., Methods: We retrospectively analyzed the medical records of children <18 years old discharged with a diagnosis of iGASi between January 2012 and December 2019. Clinical, laboratory and microbiologic data, and immunization status were retrieved. The patients were divided into severe and nonsevere groups based on their clinical presentation. The emm type was determined at the national reference center., Results: A total of 167 patients with 206 positive cultures for group A Streptococcus were identified. Hospitalizations for iGASi increased from 701 to 958 per 100,000 admissions between 2012-2015 and 2016-2019, respectively, representing an increase of 37%. The majority of the isolates were from the otolaryngologic system followed by blood, deep soft tissue and respiratory sites. Uncomplicated mastoiditis was the most common diagnosis, followed by bacteremia. Pneumonia was the main diagnosis in the severe group (39.4%)., Conclusions: The admissions because of iGASi in children <18 years old increased during the last 8 years. Surveillance systems and prospective studies should be conducted to expend our understanding of the epidemiology of iGASi in children, better assess the pathogenesis and specific risk factors and monitor changes in emm-type distribution., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: We examined the impact of insertion of the Rotavirus vaccine (RVV) into the Israeli National Immunisation Programme (NIP) on hospitalisations due to both acute gastroenteritis (AGE) and Rotavirus gastroenteritis (RVGE) in children., Methods: We retrospectively analysed the medical records of children aged <5 years admitted with a diagnosis of AGE between 2008 and 2016 in two children's hospitals in central Israel. Clinical, laboratory, microbiological data and RV immunisation status were retrieved. Data were compared before and after the introduction of the RVV into the NIP., Results: A total of 2042 children were admitted with AGE. Hospitalisations due to AGE and RVGE decreased from 3310 to 1950 and from 1027 to 585 per 100 000 admissions, respectively, after the RVV (relative risk reduction (RRR) of 41% and 43%, respectively). RV remained the most common pathogen in both study periods. There was no significant difference in the clinical course between immunised and non-immunised children admitted with RVGE., Conclusion: The introduction of the RVV to the NIP significantly reduced the admissions due to both AGE and RVGE in children <5 years. However, RV is still the most common agent for admissions due to AGE in this age group., (© 2020 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

The current outbreak of COVID-19 raging globally is taking a heavy toll on the adult population, with a rapidly growing number of newly infected and critically ill patients. However, to date, mortality rate among children is low as they mostly suffer from a mild disease. Yet, other more routinely encountered childhood diseases do not stand still and continue to be the main share of pediatricians' everyday challenges. Here we describe a case series of routinely seen pediatric diseases with delayed diagnosis due to different aspects of what we call "Corona-phobia". These cases were easily collected within a 1-week period which implies that this is a more widespread phenomenon.In conclusion, this raises the possibility that measures taken to mitigate this pandemic may be more damaging to children overall than the virus itself. We believe that pediatricians as well as policy makers should take this important aspect into consideration. What is Known: • COVID-19 manifests as a mild disease in most children; however, children are an important reservoir and may become spreaders of the disease. • Social distancing and isolation are important tools in mitigating COVID-19 transmission. What is New: • This case series describes 7 cases with delayed diagnosis of every-day pediatric diseases that were not caused by COVID-19 but were highly influenced by different aspects of "Corona-phobia". • Our objective is to highlight the possibility that measures taken to mitigate this pandemic may lead to a substantial delay in the diagnosis of other non-COVID-19 related diseases.

Objective: To describe the containment of a widespread silent outbreak of vancomycin-resistant Enterococcus faecium (VRE-fm) in the Tel-Aviv Medical Center (TASMC) neonatal intensive care unit (NICU)., Methods: Setting - an NICU, participants - 49 cases of VRE-fm-colonized neonatal inpatients., Results: A newborn was transferred from the TASMC NICU to another hospital and screened positive for VRE-fm upon arrival. All TASMC NICU patients were then immediately screened for VRE and 21/38 newborns were identified as VRE carriers. Interventional measures were strictly enforced. By the end of the outbreak, 49 cases of VRE carriage had been identified. There were no VRE clinical infections. The source of the outbreak was not identified., Conclusion: Our study highlights the importance of screening implementation in a NICU setting since this outbreak could have been prevented by active screening of all out-born transfer patients and by having adopted mandatory screening into the NICU's routine procedures. Screening for multi-drug resistant organisms upon admission of all transferred patients to the NICU has been implemented.

Background: In the absence of universal screening for congenital cytomegalovirus (cCMV) infection, the aim of this study was to assess the outcomes of a targeted screening protocol based on maternal and neonatal risk indicators., Methods: The medical records of 2,623 neonates born in our maternal hospital between June 2016 and December 2018 and screened for cCMV infection were reviewed. Among those of the included neonates, the records of 380 CMV-negative and 19 CMV-positive neonates were randomly assigned to obtain additional comparative data., Results: During the study period, a total of 63 neonates were identified as positive for cCMV, comprising 0.2% of the total birth cohort (63/28,982) and 2.4% of all neonates screened for cCMV (63/2,623). The comparative data analysis showed that suspected or confirmed CMV infection during pregnancy, maternal age, and maternal diabetes mellitus were found to be significantly associated with a positive cCMV diagnosis. Although symmetric small for gestational age and hearing screening failure contributed to the detection of some of the CMV-positive infants, these factors were not specific to this group. The results of the logistic regression model showed that the only factor that was significantly associated with an increased risk for a cCMV diagnosis was maternal serology suspected of CMV infection during pregnancy, with a regression coefficient estimate of 2.657 (adjusted p < 0.001)., Conclusions: A targeted neonatal screening protocol based on multiple maternal and neonatal risk indicators is feasible but provides limited information. Our study emphasizes the importance of universal neonatal screening for the detection of neonates with cCMV., (© 2020 S. Karger AG, Basel.)

Background: The Flavobacteriaceae family includes rare pathogens in children; Chryseobacterium indologenes and Elizabethkingia meningosepticum are the most common pathogenic species, with a wide range of clinical presentations and high mortality rate. Although rare, diagnosis is important due to inherent resistance to multiple antibiotics, especially those typically prescribed for empiric treatment of aerobic Gram-negative bacterial infections., Methods: A multicenter retrospective study conducted in 5 Israeli hospitals, describing Flavobacteriaceae bacteremia confirmed by positive blood culture from 1998 to 2018., Results: Thirteen cases were included; 9 isolates were C. indologenes. Bacteremia was nosocomial or healthcare-associated in all cases. Bacteremia was associated with young age (median, 1 year, range 24 days-17 years), with only 2 (15.4%) cases in neonates, Central line-associated bloodstream infection as a source (5/13, 38%) and malignancy (7/13, 54.8%). Thirty-day all-cause mortality was 23% (3/13). Ninety-one percent of isolates were susceptible to trimethoprim-sulfamethoxazole, 82% to piperacillin-tazobactam and 92% to ciprofloxacin., Conclusions: C. indologenes and E. meningosepticum are rare, nosocomial- or healthcare-associated pediatric bacteremia pathogens. Bacteremia was associated with young age, but in contrast to the literature, the majority of our cases were older than the neonatal age period. In addition, they were associated with central line-associated bloodstream infection and malignancy. The most adequate antibiotics according to resistance patterns were ciprofloxacin, trimethoprim-sulfamethoxazole and piperacillin-tazobactam.

Aim: Acute bacterial gastroenteritis is a major cause of morbidity and mortality, especially in the developing countries. We examined the incidence, clinical features and outcomes in the first week of life., Methods: This was a retrospective study of culture-proven bacterial gastroenteritis in newborn infants that were diagnosed between January 2011 and September 2018 in a tertiary centre in Israel., Results: There were 10 cases of culture-proven bacterial gastroenteritis, detected out of 91 stool cultures. All infants were born vaginally and nine were full-term infants. The annual incidence was 0.096 per 1000 live births. The responsible pathogen was Campylobacter in six patients, Salmonella in two and Shigella sonnei in two. The mean age of disease onset was two days of life. Antibiotics were given to five patients, but were inappropriate in two cases. Only one patient with the Shigella sonnei infection required respiratory support. All patients fully recovered., Conclusion: One in ten newborn infants with bloody stools had bacterial gastroenteritis, contradicting the low rates found in other studies and indicating the importance of considering this diagnosis. Antimicrobials active against Salmonella or Shigella should be given to newborn infants who have bloody stools and look ill., (©2019 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Objective: The diagnosis and timely treatment of shunt infections (SI) in children is of paramount importance. In some cases, the standard cerebrospinal fluid (CSF) variables will not be sufficient for an accurate diagnosis of SI. CSF lactate (LCSF) has been found to assist in differentiating bacterial from nonbacterial meningitis in non-neurosurgical patients. To the best of our knowledge, the use of lactate in diagnosing or confirming the presence of SI has not yet been discussed. The goal of the present study was to describe the role of LCSF levels in children with shunts and Ommaya reservoirs and to evaluate its role in the accurate diagnosis of shunt-related infection., Methods: We retrospectively collected data for a consecutive series of pediatric patients treated at a large tertiary pediatric neurosurgical department, for whom CSF samples from shunts had been collected during a 2-year period (2016-2017). The lactate levels were correlated with the presence of SI., Results: A total of 61 CSF samples were analyzed, with 6 SIs found. The LCSF levels and white blood cell count were both found to correlate with the presence of CSF infections. A cutoff value of ≥2.95 mmol/L reached a sensitivity of 83%, specificity of 83%, and positive predictive value of 50%. LCSF <2.95 mmol/L had a negative predictive value of 96%., Conclusions: LCSF levels can be used as an additional chemical marker for the diagnosis and confirmation of SIs. An LCSF value of <2.95 mmol/L had a high negative predictive value., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aim: This study examined the impact of the routine pneumococcal conjugate vaccination (PCV) on childhood community-acquired bacteraemia (CAB) and antibiotic resistance patterns in Israeli children., Methods: Israel added the PCV vaccine to its national immunisation programme in July 2009. We retrospectively analysed the medical records of all patients with CAB under 18 years at three children's hospitals in Tel Aviv and Jerusalem from 2007 to 2015. The microbiological data, clinical presentation, pneumococcal serotype distribution, antibiotic susceptibility and outcomes of infections were compared before and after the vaccine was introduced., Results: There were 511 904 emergency department visits and 125 922 children were hospitalised. Of those, 238 had CAB before vaccination was introduced (mean age 17 months) and 316 had CAB after the introduction (mean age 21 months). Emergency department presentations for CAB fell from 141.8 to 91.8 per 100 000 visits: a relative risk reduction (RRR) of 35%. Hospitalisations for CAB decreased from 430 to 337 per 100 000 admissions: an RRR of 22%. Hospitalisations due to Staphylococcus aureus increased significantly and penicillin nonsusceptible blood Streptococcus pneumoniae isolates decreased significantly., Conclusion: Introducing national pneumococcal conjugate vaccination significantly changed the epidemiology of CAB, with reduced antibiotic-resistant Streptococcus pneumoniae and increased hospitalisation rates for Staphylococcus aureus infections., (©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Purpose: Diagnosis of cerebrospinal fluid (CSF) infections in patients following neurosurgical procedures can be challenging. CSF lactate (LCSF) has been shown to assist in differentiating bacterial from non-bacterial meningitis in non-neurosurgical patients. The use of lactate in diagnosing CSF-related infections following neurosurgical procedures has been described in adults. The goal of this study was to describe the role of LCSF levels in diagnosing CSF-related infections among neurosurgical children., Methods: We retrospectively collected data for all pediatric patients treated at a large tertiary pediatric neurosurgical department, for whom CSF samples were collected over a 2-year period. Lactate levels were correlated with other CSF parameters, surgical parameters, presence of CSF infection, and source of CSF sample (lumbar, ventricular, or pseudomeningocele)., Results: A total of 215 CSF samples from 162 patients were analyzed. We found a correlation between lactate levels and other CSF parameters. Lactate levels displayed an inconsistent correlation with infection depending on sample origin. Irrespective of the CSF source, lactate levels could not sufficiently discriminate between those with or without infection. Lactate levels were correlated with recent surgery, and, in some of the subgroups, to the extent of blood in CSF., Conclusions: LCSF levels are influenced by many factors, including the source of sample, recent surgery, and the presence of subarachnoid or ventricular blood secondary to surgery. The added value of LCSF for diagnosing CSF infections in children with a history of neurosurgical procedures is unclear and may be influenced by the extent of blood in the CSF.

High-dose methotrexate is used to treat a range of adult and childhood cancers including osteosarcoma. Significant neurotoxicity is reported in 1% to 4.5% of patients treated with high-dose methotrexate and can present in a wide variety of symptoms. We present a case of a 14-year-old boy with a recent diagnosis of osteosarcoma who presented to the emergency department with status epilepticus, altered mental status, and very high fever secondary to methotrexate neurotoxicity. We review current literature and discuss some controversies related to this state. We also describe high fever as one of the possible symptoms associated with this condition and suggest using specific magnetic resonance imaging sequence to uncover abnormal findings related to this state. Since high-dose methotrexate is not a rare treatment in this era, we believe that in addition to oncologists, emergency department and intensive care providers should be aware of the potential role of methotrexate in causing significant neurotoxicity and include it in the differential diagnosis when treating a patient presenting with new neurological symptoms in the setting of recent high-dose methotrexate treatment.

Background: The aim of this study was to identify independent risk factors for cerebrospinal fluid shunt infection., Methods: The medical records of all patients aged 0-18 years who underwent shunt-related surgery for the treatment of hydrocephalus at the present institution between January 1996 and December 2015 were reviewed. For each case, two randomly selected controls with no shunt infection, matched for year of surgery, were chosen. Demographic clinical and microbiological data were abstracted., Results: A total of 1,570 shunt-related procedures met the inclusion criteria, yielding 68 infections (in 63 patients). The control group consisted of 132 infection-free patients. The average annual infection rate was 4.2% cases per year. The median time between shunt procedures to infection was 19 days (range, 1-2,181). On multivariate analysis, risk factors associated with increased risk for developing an infection included a history of two or more previous revisions (OR, 4.8; 95%CI: 1.5-15.9); and age <5 years (OR, 4.5; 95%CI 1.5-13.4). A neoplastic etiology for hydrocephalus was found to be a protective factor for shunt infection (P = 0.001)., Conclusions: A history of shunt revision was the most significant risk factor in the development of subsequent shunt infection. Age >5 years was a protective factor. Future efforts should focus on modalities to optimize revision procedures and reduce the risk of subsequent infection., (© 2018 Japan Pediatric Society.)

Background: Group A Streptococcus (GAS) is a rare cause of central nervous system infections., Methods: We describe 3 new cases of GAS brain abscess in previously healthy children treated by us between 2015 and 2016 and review the 5 cases reported in the literature since 1988., Results: All 8 children received early empiric antibiotic therapy and surgical intervention, and 5 made a full recovery., Conclusions: GAS brain abscess is a rare infection; however its incidence may be rising. We suggest that if patients show symptoms such as fever, vomiting and lethargy, with contiguous infection such as otitis media, mastoiditis, sinusitis or meningitis, GAS brain abscess should be suspected. Prognosis is expected to be good with early implementation of appropriate treatment.

Introduction: Widespread introduction of pneumococcal conjugated vaccines (PCVs) impacted on invasive pneumococcal disease (IPD). However, IPD reduction may not be similar in all outcomes within IPD. We assessed PCV7/PCV13 impact on pneumococcal meningitis, bacteremic pneumonia (BP) and other (non-meningitis, non-pneumonia) IPD episodes in children <5years in Israel., Methods: A prospective, population-based, active nationwide surveillance. All pneumococcal invasive episodes with positive blood/CSF cultures, July 2000 through June 2016, were included. Three sub-periods were defined: pre-PCV (2000-2008), PCV7 (2009-2011) and PCV13 (2014-2016). Incidence rate ratios (IRRs) were calculated., Results: Overall, 4321 episodes were recorded; 456 (10.6%) meningitis, 1478 (34.2%) pneumonia and 2387 (55.2%) other-IPD. In the pre-PCV period, proportion of serotypes in PCV13, but not in PCV7 (mainly serotypes 1, 5 and 19A) was higher in BP (43.3%) compared with other-IPD episodes (32.8%, p<0.001) and similar to that of meningitis (37.6%, p=0.1). The proportion of episodes in children <12months was higher in meningitis (52.1%) compared with pneumonia (23.2%) and other-IPD episodes (39.5%; p<0.001 for both). The declines of the 3 entities were not similar; Meningitis rate non-significantly declined by 24% (IRR=0.76; 95% CI 0.57-1.01), while BP and other-IPD rates significantly declined by 57% and 70%, respectively. In contrast to other entities, BP did not decline significantly after PCV7 introduction but started to decline only after PCV13 introduction. Rates of meningitis, pneumonia and other-IPD caused by PCV13-serotypes (VT13) substantially declined by 88%, 95% and 97%, respectively, comparing PCV13 and the pre-PCV periods. However, diseases caused by non-VT13 increased by 256%, 302% in meningitis and pneumonia, respectively, but only 116% in other-IPD., Conclusions: Following PCV7/PCV13 introduction, rates of episodes caused by VT13 were substantially reduced in all 3 groups. However, differences in age distribution, serotype replacement and specific serotype decrease suggest different pathogenesis and host susceptibility between the 3 entities., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Immunocompromised patients exposed to varicella may experience significant morbidity and a 7% mortality rate. Management and outcome of an outbreak of varicella infection among hospitalized pediatric hemato-oncology patients using the guidelines of the American Academy of Pediatrics Committee on Infectious Diseases are presented., Methods: This retrospective study describes an outbreak of varicella infection between February 2011 and June 2011. Data were retrieved from the patients' files. Positive polymerase chain reaction results for varicella zoster virus from vesicular skin lesions were used for the diagnosis of varicella infection., Results: Twelve pediatric hemato-oncology patients experienced 13 episodes of varicella infection, 11 underwent 1 episode each and 1 patient had 2 episodes. All exposed patients without immunity received varicella zoster immune globulins or intravenous immunoglobulin and were isolated as recommended by the guidelines. Infected patients received intravenous acyclovir. One patient with acute lymphoblastic leukemia at induction chemotherapy died. All the other patients survived., Conclusions: Our experience in the management of hospitalized immunocompromised patients exposed to varicella was that a positive IgG serology did not confer protection after exposure to varicella infection and thus can not serve as a marker for immunity. Unlike the isolation period sufficient for immunocompetent patients, crusted lesions can be contagious and thus require extended isolation for immunocompromised patients. Patients receiving rituximab are at greater risk of having persistent or recurrent disease. Studies with a larger sample size should be performed to better assess the management of immunocompromized patients exposed to varicella.

Background: Q fever is a zoonosis caused by the bacterium Coxiella burnetii (C. burnetii) with a worldwide distribution. Our aim was to assess the epidemiology, clinical manifestations and treatment regimens of chronic Q fever infections in Israeli children during the past 25 years., Methods: Cases were collected from the national Q fever reference laboratory database. Demographic, epidemiologic and clinical data were reviewed using a structured questionnaire sent to the referring physician. Cases were defined according to the new Dutch Consensus Guidelines., Results: A total of 16 children originating from all regions of the country were found positive for chronic Q fever infections. The most common infection site was bone or joint (8/16, 50%), all in previously healthy children. Endovascular infections were found in 5 children (31%), all with an antecedent cardiac graft insertion. According to the new Consensus Guidelines, 9 children (56%) had a proven infection, 3 (19%) a probable infection and 4 (25%) a possible chronic Q fever infection. Almost all cases were treated with a long-term antibiotic regimen, often necessitating a change in medication because of persistent or rising titers., Conclusions: Although pediatric chronic Q fever infections are rare, incidence has been rising. The most common infection site was bone or joint. A high index of suspicion is necessary, even in cases of previously healthy children without a possible exposure history. Use of the relatively new diagnostic tools in combination with serologic methods is helpful in diagnosing proven cases. There is no consensus as to the selection or duration of antibiotic treatment.

Purpose: Chronic granulomatous disease (CGD) is an innate immune deficiency disorder of phagocytes, resulting from mutations in the components of the NADPH oxidase complex that impair the synthesis of oxygen radicals, thus rendering patients susceptible to recurrent infections and excessive hyperinflammatory responses. The most common autosomal recessive form of CGD is p47 phox deficiency, which is often clinically milder than the more common X-linked recessive form. Here, we report data on genetics, clinical and biochemical findings in 17 CGD patients of Kavkazi origin with the nonsense mutation c.579G>A in the NCF1 gene, leading to p47 phox deficiency., Methods: Diagnosis was based on detailed clinical evaluation, respiratory burst activity by cytochrome c reduction and dihydrorhodamine-1,2,3 (DHR) assay by flow cytometry, expression of p47 phox by immunoblotting and molecular confirmation by DNA sequence analysis., Results: Twelve male and five female patients with median age at onset of 2.5 years (range 1 day to 9 years) were included in the study. The present cohort displays an encouraging 88% overall long-term survival, with median follow-up of 17 years. Clinical manifestations varied from mild to severe expression of the disease. Correlation between genotype and phenotype is unpredictable, although the Kavkazi patients were more severely affected than other patients with p47 phox deficiency., Conclusions: Kavkazi CGD patients harbor a common genetic mutation that is associated with a heterogeneous clinical phenotype. Early diagnosis and proper clinical management in an experienced phagocytic leukocyte center is imperative to ensure favorable patient outcome. New treatment strategies are ongoing, but results are not yet conclusive.

Objective  To assess the role of placental cultures in cases of preterm premature rupture of membranes (PPROM) complicated by chorioamnionitis and to determine the effect of positive cultures on short-term neonatal outcomes. Design  A retrospective single-center study. The medical records of all women with PPROM between January 1, 2011, and December 31, 2015, were reviewed. Cases were divided into placental culture positive (group A) and placental culture negative (group B) groups. Maternal and pregnancy characteristics as well as short-term neonatal outcomes were compared between groups. Results  During the 5-year study period, 61 cases of clinical chorioamnionitis complicating PPROM were diagnosed: 25 cases were culture positive (group A) and 36 were culture negative (group B). Neonatal outcome measures, including Apgar score at 5 minutes ( p  = 0.028; odds ratio [OR]: 5.27; confidence interval [CI]: 1.19-23.34), respiratory distress syndrome ( p  = 0.026; OR: 4.11; CI: 1.18-14.25), and neonatal infection ( p  < 0.0001; OR: 11.59; CI: 3.37-39.87) were significantly more common in group A newborns, regardless of gestational age at delivery as was the composite neonatal outcome ( p  = 0.017; OR: 7.35: CI: 1.42-37.79). Placental isolates were primarily Streptococci and Escherichia coli . Conclusion  Placental cultures may be an essential predictor of neonatal morbidity in PPROM and may contribute to the modification of neonatal treatment., Competing Interests: Conflict of Interest: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Chronic granulomatous disease (CGD) is an innate immunodeficiency with a genetic defect of the nicotinamide adenosine dinucleotide phosphate, reduced, oxidase components. This leads to decreased reactive oxygen species (ROS) production, which renders patients susceptible to life-threatening infections. Over the course of 30 years, we diagnosed CGD in 84 patients from 61 families using functional, molecular, and genetic studies. The incidence of CGD in Israel is 1.05 per 100,000 live-births in the Jewish population and 1.49 in the Israeli Arab population. We diagnosed 52 patients (62%) with autosomal recessive inheritance (AR-CGD) and 32 (38%) with X-linked recessive inheritance (XLR-CGD). Consanguinity was detected in 64% of AR-CGD families (14% in Jews and 50% in Israeli Arabs). We found 36 different mutations (23 in XLR-CGD and 13 in AR-CGD patients), 15 of which were new. The clinical spectrum of CGD varied from mild to severe disease in both XLR and AR forms, although the AR subtype is generally milder. Further, residual ROS production correlated with milder clinical expression, better prognosis and improved overall survival. Patients with recurrent pyogenic infections developed fibrosis and hyperinflammatory states with granuloma formation. The management of CGD has progressed substantially in recent years, evolving from a fatal disease of early childhood to one of long-term survival. Our present cohort displays an encouraging 81% overall long term survival. Early hematopoietic stem cell transplantation is advisable before tissue damage is irreversible. Successful transplantation was performed in 18/21 patients. Therapeutic gene modification could become an alternative cure for CGD. Am. J. Hematol. 92:28-36, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

To report the experience of a large tertiary care pediatric center during a period of increasing Streptococcus pneumoniae antimicrobial resistance before the introduction of pneumococcal vaccine in Israel. Retrospective chart review of children diagnosed acute mastoiditis (AM) between January 1997 and December 2007. The children were divided into 4 age groups (6-11, 12-23, 24-35, and 36-40 months), and each group was compared with the others. A total of 198 AM episodes were recorded during the 10-year study period. The most prevalent pathogen was S. pneumonia, with a very low (15%) penicillin resistance rate (minimal inhibitory concentration ≥ 2). Complications were more prevalent in the 12- to 23-month age group. The number of AM cases increased during the study period. Penicillin resistance did not play an important role in determining the morbidity before the introduction of pneumococcal conjugate vaccine.

Background: Prematurity is an important risk factor for the fulminate form of neonatal enteroviral infection. Pulmonary hemorrhage is a morbid complication that should be anticipated and managed aggressively due to its fatal outcome., Objective: To emphasize the significance of pulmonary hemorrhage as a complication of severe enterovirus infection in preterm neonates., Study Design: This report is a description of the clinical history, medical management and clinical outcomes of two pairs of preterm twin newborns (30 weeks and 36 weeks) with fulminant infection due to Coxsackievirus B (CBV) infection., Results: Maternal fever was reported in both deliveries and it was a factor in the decision for urgent cesarean section of the 30-week twins. Three of the four infants failed to survive. Their clinical course involved multiple organ system failure complicated with profound disseminated intravascular coagulopathy and pulmonary hemorrhage. Pulmonary bleeding leading to hypovolemic shock and respiratory failure was the direct cause of death in two cases., Conclusions: This small series of preterm neonates with the diagnosis of CBV sepsis highlights the importance of correct diagnosis of maternal enterovirus infection in order to extend pregnancy and allow the fetus time to passively acquire protective antibodies. This report emphasizes the morbid complication of pulmonary hemorrhage as a result of enterovirus infection that should be anticipated and managed aggressively due to its potentially fatal outcome. Moreover, evaluation and observation of the asymptomatic twin is recommended in order to detect early signs of infection and deterioration in that sibling as well., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Aim: The varicella-zoster virus causes infections that are often mild but can cause substantial morbidity and mortality in otherwise healthy children. We examined trends in varicella-related hospitalisations before and after the implementation of a national two-dose varicella vaccination programme in Israel in September 2008., Methods: This retrospective chart review, performed at three tertiary care paediatric hospitals in greater Tel Aviv, compared data from 2004 to 2008 and 2009 to 2012, before and after the varicella programme was launched. It included all children to the age of 18 who were hospitalised for conditions associated with the varicella infection., Results: After the vaccination programme was introduced, the number of children hospitalised for varicella fell by 63% (p < 0.5), from 38.9 to 14.5 per 10 000, and there was a 75% reduction in children aged one to six. During the same period, the percentage of hospitalised children who were immunocompromised rose from 9.7% to 18.4% (p < 0.05). The most common complications were soft-tissue infections (60%), and the most prevalent pathogens were Group A β-haemolytic streptococcus (53%) and Staphylococcus aureus (32%)., Conclusion: The introduction of a two-dose immunisation programme dramatically decreased the varicella burden in Israel, leading to a major reduction in hospitalisation admissions linked to the infection., (©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: Delayed antibiotic treatment for acute otitis media (AOM) is recommended for children >6 months with nonsevere illness, no risk factors for complications or history of recurrent AOM. This study evaluates relationship between delayed antibiotic treatment for antecedent AOM and severity of subsequent acute mastoiditis admission., Methods: A prospective observational study of children aged 0-14 years admitted with acute mastoiditis to 8 hospitals between 2007 and 2012 calculates rates of severe acute mastoiditis admission [defined by ≥1 of the following: complication (mastoid subperiosteal abscess, brain abscess and sagittal vein thrombosis), need for surgical procedure and duration of admission >6 days].Severe acute mastoiditis admissions in children with antecedent AOM treated with immediate antibiotics were compared with those with delayed antibiotic treatment., Results: Antecedent AOM was diagnosed in 216 of 512 acute mastoiditis admissions (42.1%), of whom 159 (73%) immediately received antibiotics, and 57 (27%) had delayed antibiotic treatment. Higher rate of recurrent AOM was noted in the immediate compared with delayed antibiotic treatment group (29% vs. 8.7%, P = 0.0021). Complication rates were 19.5% versus 10.5% (P = 0.12), rates of surgical procedures required, 30% versus 10% (P = 0.0033); admission rates >6 days, 37% versus 29% (P = 0.28) for immediate antibiotic therapy and delayed antibiotic treatment. On logistic regression analysis, immediately treated AOM patients had increased need for surgery for acute mastoiditis with adjustment for history of recurrent AOM (relative risk: 3.2, 95% confidence interval: 1.4-7.0)., Conclusions: Delayed antibiotic treatment for antecedent AOM is not associated with an increase in severity parameters in subsequent acute mastoiditis admission.

Objectives: The clinical characteristics, pathogens, and outcome were analyzed to investigate the etiology of acute pediatric encephalitis in 2 tertiary pediatric medical centers in Israel., Methods: A retrospective study among children aged 1 month to 18 years hospitalized with the diagnosis of acute encephalitis between January 1999 and December 2009. Data on presenting symptoms, clinical findings, microbiological, virologic, electroencephalographic and neuroimaging studies, laboratory results, and hospital course were retrieved from the medical records and the computerized microbiology database., Results: Forty-four children were included. An etiologic agent was identified in 11 (25%): Mycoplasma pneumoniae (n = 2), enterovirus (n = 3), herpes simplex virus (HSV) (n = 1), Epstein-Barr virus (n = 2), human herpes virus 6 (n = 1), influenza virus type A (n = 1), and varicella zoster virus (n = 1). Presenting features included fever (90% of patients), seizures (39%), focal neurological signs (18%), and decreased consciousness (67%). Diagnostic findings included pleocytosis in the cerebrospinal fluid (76% of patients), electroencephalographic abnormalities (78%), and neuroimaging abnormalities (34%). All patients were treated with acyclovir until negative result for HSV polymerase chain reaction was received from cerebrospinal fluid, the child with HSV encephalitis was treated with intravenous acyclovir for 3 weeks. The outcomes at the time of discharge were: normal (66%), motor difficulties (14%), global neurological deficits (7%), visual defects (2%), and hearing impairment (2%) and no deaths., Conclusions: The etiology of acute encephalitis remains unknown in the majority of cases. There was no correlation between adverse outcome and a specific etiologic agent. The high morbidity rate may suggest that current therapeutic modalities may not be sufficient.

Background: Extreme leukocytosis, defined as a peripheral white blood cell count greater than 25,000/mm, may alarm clinicians and prompt extensive evaluation in infants with fever, especially in the pediatric emergency department., Methods: We reviewed data from children aged 3 to 36 months with extreme leukocytosis, fever and the risk of serious bacterial infections (SBI) at our institution from July 2010 to December 2012, a period after the universal introduction of pneumococcal vaccine., Results: Serious bacterial infection was recorded in 57 (39%) of the 147 infants. The most common SBI were segmental or lobar pneumonia, in 28 (19%) patients, and urinary tract infection in 16 (10.9%) patients. Three patients had positive blood cultures, corresponding to a bacteremia rate of 2%. C-reactive protein was significantly higher in the SBI group than in the non-SBI group., Conclusions: All well-looking febrile infants with white blood cell greater than 25,000/mm should undergo a chest radiograph unless there are clear physical findings that indicate a different etiology. Urine culture should be considered in women. C-reactive protein can have an added value in the differential diagnosis.