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Worldwide rotavirus vaccination has resulted in a substantial decrease in rotavirus-induced severe gastroenteritis and related hospitalizations among children. Still, the characterization of patients warranting hospitalization needs to be further elucidated. The purpose of the study is to compare the clinical and laboratory features of children hospitalized with acute rotavirus infection before and after the introduction of routine vaccination.This is a retrospective observational study. Participants were pediatric patients who presented to the Bnai Zion Medical Center pediatric emergency department and were diagnosed with rotavirus acute gastroenteritis between 2017 and 2019.During the pre-vaccination period (2007-2009), 114 infants and young children (median age: 14 months, range: 1-72 months; 59 male, 55 female) were hospitalized for rotavirus-induced acute gastroenteritis with a rate of 11.71 positive rotavirus tests per 1000 emergency room visits. In the post-vaccination period (2012-2019), 168 infants and young children (median age: 17 months, range: 0-84 months; 90 male, 78 female) were hospitalized with a rate of 4.18 positive rotavirus tests per 1000 emergency room visits. There were no statistical differences between the two groups in gender, breast-feeding rates and sibling(s). The proportion of cases with moderate-to-severe dehydration was higher in the post-vaccination children than in the pre-vaccination children.Rates of rotavirus-attributed acute gastroenteritis hospitalizations declined from the pre- to the post-vaccination period. Higher rates of dehydration were found in the post-vaccination children. Ongoing surveillance is warranted to better understand the implications of the vaccine.

Objectives Healthcare workers (HCWs) are considered an important target group for the COVID‐19 vaccines. The current study assesses the knowledge and attitudes of Israeli HCWs regarding COVID‐19 immunization, and how various occupational and demographic factors may underlie COVID‐related knowledge and attitudes differences. Methods Following a pre‐test to validate measures, a cross‐sectional online anonymous survey was distributed to HCWs using a snowball sampling method. Results The survey was completed by 714 participants (mean age 39.9; range 18–74; 447 female), 52% doctors, 32% nurses, and the remainder by paramedical staff. Of the respondents, 553 (77.4%) answered the question are you in favor of getting the COVID‐19 vaccine, 105 (14.7%) were not sure, and 56 (7.8%) were not in favor. Doctors had higher odds of agreement as compared to both nurses (p

To investigate the association of viral load (VL) with (i) tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein-10, C-reactive protein, and a combinatorial score (BV score), and (ii) clinical severity.In this prospective, multicentre cohort substudy, children with respiratory tract infection or fever without source were enrolled. VL for influenza virus, rhinovirus, respiratory syncytial virus, and adenovirus was measured from nasopharyngeal swabs. The reference standard diagnosis was established based on expert panel adjudication.Of 1140 recruited patients, 333 had a virus monodetection. VL for the aggregated data set correlated with TRAIL and IP-10 levels, with the length of oxygen therapy, and inversely with the BV score. At a single viral level, only the influenza VL yielded a correlation with TRAIL, IP-10 levels, and the BV score. Children with a viral reference standard diagnosis had significantly higher VL than those with bacterial infection (p = 0.0005). Low TRAIL (incidence rate ratio [IRR] 0.6, 95% confidence interval [CI] 0.39-0.91) and young age (IRR 0.62, 95% CI 0.49-0.79) were associated with a longer hospital stay, while young age (IRR 0.33, 95% CI 0.18-0.61), low TRAIL (IRR 0.25, 95% CI 0.08-0.76), and high VL (IRR 1.16, 95% CI 1.00-1.33) were predictive of longer oxygen therapy.These findings indicate that VL correlates with biomarkers and may serve as a complementary tool pertaining to disease severity.

We retrospectively examined the yield of a cerebrospinal fluid (CSF) multiplex real-time PCR assay of febrile young infants undergoing a full sepsis work-up. Eighty infants were included in the study: Forty-nine (61%) neonates and 31 (39%) 29–90 day-old patients were included in the study. A viral pathogen was detected in 59% (47/80) of the samples, human enterovirus in 53% (42/80) and Human parechovirus in 6% (5/80). The CSF of nearly half of the subjects with CNS infection was without pleocytosis; all CSF cultures were negative. Multiplex PCR CSF testing enhances the diagnosis of pathogen-specific viral CNS infection among febrile young infants.

Background Little is known about the impact of social interactions on iatrogenesis and lapses in patient safety. Methods This field-based experience-sampling study of primarily nurses in a general hospital explored the impact of rudeness on patient safety performance, state depletion (that is, exhaustion of mental energy for reflective behavior), and team processes (for example, information sharing). Objective measures of performance were compliance with hand hygiene and medication preparation protocols, as well as archival reports of adverse events. Data were analyzed by department shift (480 shifts [15 days] in 16 departments). Results A total of 231 rudeness incidents were reported in 98 shifts, most stemming from a patient or family. Compliance with hand hygiene was significantly lower up to 24 hours after rudeness exposure (p = 0.03). Rudeness significantly increased team members' state depletion (p = 0.002) and was associated with decreased information sharing (p = 0.046) but was not directly associated with adverse events or level of compliance with medication and hand hygiene protocols. However, the adverse indirect effect of shifts' temporal proximity to rudeness on poor compliance with medication preparation and team members' information sharing via state depletion was significant. Rudeness exposure was also associated with increased rate of adverse events in the subsequent 24 hours, although this association was not statistically significant. Conclusion Rudeness exposure was associated with reduced team member compliance with infection control and medication protocols via greater team member state depletion and diminished information sharing.

The aim of our study was to evaluate the long-term outcomes of pediatric migraine and TTH in a clinical setting. We conducted a cohort study. Pediatric patients who visited the pediatric neurology clinic due to diagnoses of migraine or TTH were contacted by phone 8–10 years after their initial diagnosis and interviewed about their outcomes. Of 147 children, we were able to reach 120 (81%) patients. Of these 120 patients, 59 were seen initially due to migraine and 61 due to TTH. For the migraine patients, headaches improved in 48 (81.4%) and worsened in four (6.8%). Regarding diagnosis at follow-up, 59% still had migraine, 17% had TTH, and 23% were headache-free. Aura and photophobia were significantly associated with persistence of a migraine diagnosis. For the TTH patients, headaches improved in 49 (81.7%) and worsened in nine (15.0%). Regarding diagnosis at follow-up, 36.7% still had TTH, 18.3% had migraine, and 45% were headache-free. Of the patients with TTH, 36.7% retained their initial diagnosis compared to 59.3% among the migraine patients. Most pediatric patients presenting with migraine or TTH will experience a favorable outcome over 10 years, with TTH patients having twice the chance of complete resolution.

Objectives Identifying infection aetiology is essential for appropriate antibiotic use. Previous studies showed a host-protein signature consisting of TNF-related apoptosis-induced ligand (TRAIL), interferon gamma-induced protein-10 (IP-10), and C-reactive protein (CRP) can accurately differentiate bacterial from viral infections. Methods This prospective, multicentre cohort study titled “AutoPilot-Dx”, aimed to validate signature performance and estimate its potential impact on antibiotic use across a broad paediatric population (>90 days to 18 years) with respiratory tract infections, or fever without source, at emergency departments and wards in Italy and Germany. Infection aetiology was adjudicated by experts based on clinical and laboratory investigations, including multiplex PCR and follow-up data. Results In total, 1140 patients were recruited (2/2017–12/2018), of which 1008 met eligibility criteria (mean age 3.5 years, 41.9% female). Viral and bacterial infections were adjudicated for 628 (85.8%) and 104 (14.2%) children, respectively; 276 patients were assigned an indeterminate reference standard outcome. For the 732 children with reference standard aetiology, the signature discriminated bacterial from viral infections with sensitivity of 93.7% (95% CI, 88.7–98.7), specificity of 94.2% (92.2–96.1), positive predictive value of 73.0% (65.0–81.0), negative predictive value of 98.9% (98.0–99.8), and 9.8% equivocal test results. The signature performed consistently across different patient subgroups and detected bacterial immune response in viral PCR positive patients. Conclusions The findings validate high diagnostic performance of the TRAIL/IP-10/CRP signature in a broad paediatric cohort and support its potential to reduce antibiotic overuse in children with viral infections. Trial registration Clinicaltrials.gov identifier: NCT03052088.

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, We assessed pediatric COVID-19 in 20/26 Israeli hospitals. Overall, 568 cases (82% mild disease, 8% moderate/severe disease, and 10% PIMS), representing

We retrospectively examined the yield of a cerebrospinal fluid (CSF) multiplex real-time PCR assay of febrile young infants undergoing a full sepsis work-up. Eighty infants were included in the study: Forty-nine (61%) neonates and 31 (39%) 29-90 day-old patients were included in the study. A viral pathogen was detected in 59% (47/80) of the samples, human enterovirus in 53% (42/80) and Human parechovirus in 6% (5/80). The CSF of nearly half of the subjects with CNS infection was without pleocytosis; all CSF cultures were negative. Multiplex PCR CSF testing enhances the diagnosis of pathogen-specific viral CNS infection among febrile young infants.

Background Most infants with congenital cytomegalovirus (cCMV) have no overt manifestations at birth, yet may later develop CMV-related sensorineural hearing loss (SNHL). With targeted screening, many asymptomatic neonates are missed and lose the opportunity for timely anti-viral treatment to ameliorate SNHL. Saliva is the preferred screening specimen given its ease of collection. Objectives Assess a pooled saliva CMV DNA detection technique for cCMV screening of healthy full-term neonates. Study design We conducted a prospective laboratory CMV PCR screening study in a secondary hospital from March-June 2019. Saliva specimens were obtained from 1000 newborns two-four hours after birth. Specimens were analyzed for CMV DNA with a real-time PCR platform (Altona) in pools of 10 and individually (40 μL and 400 μL, respectively). Neonates with positive saliva CMV DNA detection required urine CMV PCR testing to confirm cCMV diagnosis. Results From the 1000 saliva samples, there were 6 urine-confirmed cCMV cases, yielding a prevalence rate of 0.6 %. The specificity was high for both pooled and individual saliva sampling (99.9 % and 98.1 %, respectively). The positive predictive value of the pooled sample was 85.7 %, compared to 24.0 % for a single saliva sample. Conclusions Pooling saliva of healthy newborns appears to be a reliable method to identify asymptomatic cCMV infection when positive results are confirmed by urine CMV DNA. Pooling in sizes appropriate to the cCMV prevalence rate may improve the laboratory workflow and decrease costs. Further studies should evaluate the clinical implications of this widespread cCMV pooled screening technique.

Background Food allergies (FAs) are on the rise worldwide. A previous cross-sectional study from 2002 in Israel estimated the prevalence of IgE-mediated FA among young children at 0.85%. Although sesame was found to be a common allergen, peanuts were found to be a rare allergen. Objective To determine the prevalence and distributions of IgE-mediated FAs among young children in Israel compared with previous data. Methods A total of 1932 young children (56% males, 44% females) with a mean age of 22.4 months (range, 18-30 months) were sequentially recruited from 15 government family health care centers in north Israel. Parents completed a questionnaire with 2 screening questions for suspected FA. Subjects with suspected FA underwent further evaluation including telephone interview, skin prick tests, and oral food challenge as needed. Results After analyzing the questionnaires, 146 subjects were suspected to have FA. Seventy-nine subjects were excluded by telephone interview and 13 were excluded on the basis of negative oral food challenge. We identified 54 of 1932 (2.8%) young children with 75 IgE-mediated FAs. Thirty-nine of 54 (72.2%) had allergy to 1 food and 9 (16.6%) to 2 foods. The most common food allergens were cow's milk (1%), eggs (0.88%), sesame (0.93%), tree nuts (0.57%), peanuts (0.2%), and fish (0.2%). Conclusions The prevalence of IgE-mediated FA among young children in Israel has increased dramatically from 0.85% to 2.8%. The relative prevalence of the most common food allergens is similar to that identified in 2002, with a high prevalence of sesame FA and low prevalence of peanut FA.

Bordetella pertussis is prevalent among infants, but its diagnosis is complicated by the fact that its signs and symptoms overlap with respiratory viruses. Indeed, when evaluating the etiology of infants less than 1 year of age suspected of having pertussis, we found that respiratory viruses frequently mimic B. pertussis and are more likely to be the causative agent.

Bacterial and viral lower respiratory tract infections (LRTIs) are often clinically indistinguishable, leading to antibiotic overuse. We compared the diagnostic accuracy of a new assay that combines 3 host-biomarkers (TRAIL, IP-10, CRP) with parameters in routine use to distinguish bacterial from viral LRTIs. Study cohort included 184 potentially eligible pediatric and adult patients. Reference standard diagnosis was based on adjudication by an expert panel following comprehensive clinical and laboratory investigation (including respiratory PCRs). Experts were blinded to assay results and assay performers were blinded to reference standard outcomes. Evaluated cohort included 88 bacterial and 36 viral patients (23 did not fulfill inclusion criteria; 37 had indeterminate reference standard outcome). Assay distinguished bacterial from viral LRTI patients with sensitivity of 0.93±0.06 and specificity of 0.91±0.09, outperforming routine parameters, including WBC, CRP and chest x-ray signs. These findings support the assay's potential to help clinicians avoid missing bacterial LRTIs or overusing antibiotics.

Background Identifying bacterial coinfection in influenza patients can be difficult as the symptoms of simple influenza versus mixed infections are often similar, leading to antibiotic overuse. A new host-response assay (ImmunoXpert™) that integrates the levels of three proteins (TRAIL, IP-10, and CRP) was shown to exhibit high performance in distinguishing between bacterial and viral disease in two double-blind validation studies. Here we sought to evaluate its ability to differentiate between simple influenza and influenza with bacterial coinfection. Material/Methods The study population included 653 febrile pediatric and adult patients prospectively recruited in the ‘Curiosity’ study. Patient etiology (simple viral versus mixed infection) was determined by unanimous expert adjudication based on comprehensive clinical, laboratory and radiological assessment. Influenza strains (A or B) were detected using multiplex PCR applied to nasal swabs (Seeplex-RV15). We compared the expert panel diagnosis with the assay that gives three possible outcomes: viral, bacterial (including viral with bacterial coinfection) or equivocal. An equivocal outcome does not provide diagnostic information and is observed in ∼10% of cases. Results Out of 653 patients, 51 had positive influenza detection and unanimous expert diagnosis: 44 simple viral infections and 7 influenza with bacterial coinfections (Figure 1). Antibiotics were prescribed to all 7 cases of influenza with bacterial coinfection and to 20/44 cases adjudicated as simple viral infections, indicating an overuse rate of 45%. The assay correctly classified 40 of the 44 simple viral cases (out of the remaining 4, 2 were assigned viral with bacterial coinfection and 2 received equivocal outcomes) as well as 5 of the 7 viral with bacterial coinfection cases (the remaining 2 received equivocal outcomes) supporting the assay’s potential to reduce antibiotic overuse 5-fold (from 45% to 4/44=9%, P Conclusion The host-response assay can differentiate between simple influenza and influenza patients with bacterial coinfection, with potential to reduce antibiotic overuse. Utility studies are warranted to demonstrate that the assay can safely assist physicians in correct management of influenza patients

Background Bell's palsy is a peripheral paralysis of the seventh cranial nerve, whose etiology is unknown. Using polymerase chain reaction technology, it is possible to sample accessible body fluids and identify possible viral factors. The purpose of this research is to investigate its connection to the herpes virus family by testing for the presence of the virus in the saliva and tear fluid of Bell's palsy patients. Methods Saliva and tears were collected from 42 children and adolescents suffering from idiopathic facial nerve paralysis. Polymerase chain reaction was used to test for the presence of the viruses Epstein-Barr virus, cytomegalovirus, herpes simplex virus 1 and 2, varicella zoster virus and human herpes virus 6 (HHV-6). Samples were also taken from a control group without paralysis. A second specimen was taken from patients who tested positive for HHV-6 several months after their recovery. Results Of the 42 patients in the study group, 71% (30 patients) tested positive for HHV-6, compared with only 37% of the control group (P = 0.001). The prevalence of the other 5 viruses tested was low-herpes simplex virus 1: 9.5%, Epstein-Barr virus: 9.5%, cytomegalovirus: 4.8%, varicella zoster virus: 2.3% and herpes simplex virus 2: 0%. Twenty-four of the 30 patients who were HHV-6-positive during their illness were reexamined following recovery. Only 13 patients (54.2%) excreted the virus after recovery from the paralysis. Conclusions Herpes 6 virus appears to play some role in the etiology of facial nerve paralysis. The virus was detected in the saliva of children during acute illness and decreased with resolution. Our research opens new insights linking HHV-6 to the etiology of Bell's palsy in children.

BACKGROUND AND OBJECTIVES: Exposure to negative social interactions (such as rudeness) has robust adverse implications on medical team performance. However, little is known regarding the effects of positive social interactions. We hypothesized that expressions of gratitude, a prototype of positive social interaction, would enhance medical teams’ effectiveness. Our objective was to study the performance of NICU teams after exposure to expressions of gratitude from alternative sources. METHODS: Forty-three NICU teams (comprising 2 physicians and 2 nurses) participated in training workshops of acute care simulations. Teams were randomly assigned to 1 of 4 conditions: (1) maternal gratitude (in which the mother of a preterm infant expressed gratitude to NICU teams, such as the one that treated her child), (2) expert gratitude (in which a physician expert expressed gratitude to teams for participating in the training), (3) combined maternal and expert gratitude, or (4) control (same agents communicated neutral statements). The simulations were evaluated (5-point Likert scale: 1 = failed and 5 = excellent) by independent judges (blind to team exposure) using structured questionnaires. RESULTS: Maternal gratitude positively affected teams’ performances (3.9 ± 0.9 vs 3.6 ± 1.0; P = .04), with most of this effect explained by the positive impact of gratitude on team information sharing (4.3 ± 0.8 vs 4.0 ± 0.8; P = .03). Forty percent of the variance in team information sharing was explained by maternal gratitude. Information sharing predicted team performance outcomes, explaining 33% of the variance in diagnostic performance and 41% of the variance in therapeutic performance. CONCLUSIONS: Patient-expressed gratitude significantly enhances medical team performance, with much of this effect explained by enhanced information sharing.

Delayed antibiotic treatment for acute otitis media (AOM) is recommended for children6 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.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 admission6 days].Severe acute mastoiditis admissions in children with antecedent AOM treated with immediate antibiotics were compared with those with delayed antibiotic treatment.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 rates6 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).Delayed antibiotic treatment for antecedent AOM is not associated with an increase in severity parameters in subsequent acute mastoiditis admission.

Non-typable Haemophilus influenzae (NTHi) is emerging as an important cause of invasive disease in immunized children. We describe a healthy, fully immunized 4-year old child who presented with bacteremia due to NTHi without overt acute otitis media (AOM), and subsequently developed severe mastoiditis complicated by sigmoid sinus thrombosis. Although, mastoiditis is typically regarded as a complication of AOM, those cases without antecedent AOM may represent an entirely different pathophysiological process with NTHi bacteremia seeding the mastoid. We present another example of the potential invasiveness of NTHi with a temporal sequence of events whereby NTHi bacteremia seeds the mastoid. This may represent novel sequelae of NTHi infection.

Background The Centers for Disease Control and Prevention recommend tetanus–diphteria–acellular pertussis (Tdap) immunization during pregnancy, preferably at 27–36 weeks gestation. Aims First, to assess the relative avidity index (RAI) of umbilical cord immunoglobulin G (IgG) to pertussis toxin (PT) for newborns of women immunized with Tdap during late pregnancy as compared to unimmunized women. Second, to assess whether there is a preferential period of gestational Tdap immunization that provides the highest RAI of umbilical cord IgG to PT. Methods RAI of IgG to PT was assessed via an adapted ELISA using NH 4 SCN as a dissociating agent. Results We found that newborns of women immunized with Tdap during late pregnancy ( n = 52) had higher mean RAI of umbilical cord IgG to PT than those of unimmunized women ( n = 8), 73.77% ± 12.08 (95% CI, 70.41–77.13) vs. 50.23% ± 21.32 (95% CI, 32.41–68.06), p +6 weeks gestation ( n = 20) when compared with newborns of women immunized at 31–36 weeks ( n = 22) and >36 weeks ( n = 7), 79.53% ± 5.61 (95% CI, 76.91–82.16) vs. 71.56% ± 12.58 (95% CI, 65.98–77.14) vs. 63.93% ± 17.98 (95% CI, 47.31–80.56), p Conclusion Gestational Tdap immunization between 27 and 30 +6 weeks resulted in the highest avidity of IgG to PT conveyed at delivery as compared with immunization beyond 31 weeks gestation. Future studies should be conducted to confirm our findings to optimize pertussis-controlling strategies.

Center for Disease Control and Prevention recommends vaccination of pregnant women with tetanus-diphtheria-acellular pertussis (Tdap).To measure pertussis specific antibodies, total protein and their ratio in breast milk following gestational Tdap vaccination.Women who received Tdap after the 20th week of pregnancy were recruited and unvaccinated women served as controls. Breast milk total protein, immunoglobulin A (IgA) to pertussis toxin (PT), filamentous hemagglutinin (FHA) and immunoglobulin G (IgG) to PT, FHA and pertactin (PRN) were measured. To overcome the dilution that occurs in the transition from colostrum to mature breast milk, we calculated pertussis specific antibody to total protein ratio.Pertussis specific IgA was the predominant pertussis immunoglobulin in the colostrum of Tdap vaccinated women with the geometric mean concentrations (GMCs) of IgA to FHA higher than for IgA to PT, 24.12 ELISA units/milliliter (EU/mL) vs. 8.18EU/mL, respectively, p0.004. There were differences between the vaccinated women and controls in the GMCs of IgA to FHA and IgG to PRN in the colostrum, 24.12EU/mL vs. 6.52EU/mL, p=0.01 and 2.46EU/mL vs.0.6EU/mL, p=0.03, respectively. The GMCs of total protein showed significant decline over 8 weeks in the vaccinated women and controls, p0.004. Among vaccinated women, there was significant decline in the GMCs of IgA to PT and FHA over 8 weeks, p0.001. The geometric mean ratio of IgA to FHA to total protein also declined significantly over 8 weeks in the vaccinated women, p0.01, demonstrating a true decrease, however, pertussis IgA was measurable at 8 weeks.Select colostrum pertussis antibody levels were significantly higher among women vaccinated with Tdap during pregnancy compared with unvaccinated women. Among vaccinated women, maximal levels of pertussis specific IgA were in the colostrum but still detected at 8 weeks. Lactation may augment infant's protection against pertussis.

Background A major challenge in the effective management of children with RSV infection is the clinical difficulty of distinguishing a simple viral from viral–bacterial coinfections. As a result, despite the low rates of viral–bacterial coinfection, RSV patients are often prescribed antibiotics with recent reports demonstrating more than 60% antibiotic overuse rates (Van Houten et al. 2018). Here, we examined whether a host-immune signature combining the viral-induced proteins TRAIL and IP-10 with the bacterial-induced protein CRP (ImmunoXpert; Oved et al. 2015) can distinguish simple viral from viral–bacterial coinfection in RSV patients. Methods We studied 402 febrile children enrolled as part of “Curiosity,” a prospective study designed to develop and validate the host-immune signature. Infection etiology—viral or viral-bacterial coinfection—was determined by a panel of experts following a review of patients’ clinical, laboratory, radiological, microbiological, and follow-up data. RSV strains were detected using a respiratory multiplex PCR applied to nasal swabs (Seeplex-RV15). Results Out of the 402 children with suspected acute infection 29 had a positive RSV detection (Figure 1); of them, 27 had a unanimous expert panel etiology determination: 24 viral and 3 viral–bacterial coinfections. Out of the 24 patients unanimously assigned viral by the expert panel, 13 were given antibiotics, indicating a 54% antibiotic overuse rate. The host-immune signature correctly identified all 3 viral-bacterial coinfection cases, as well as 22 out of the 24 (92%) simple viral patients. This finding supports that the signature has the potential to reduce antibiotic overuse by 6.5-fold (from an overuse of 13/24 = 54% to 2/24 = 8%, P < 0.001). Conclusion Our results demonstrate high antibiotic overuse rates for RSV patients, consistent with previous reports. The host-immune signature correctly distinguished simple viral from viral–bacterial coinfection and therefore may have the potential to aid physicians in the correct management of children with RSV infection. Implementation studies are required to evaluate its utility in safely decreasing unnecessary antibiotic use for RSV patients. Disclosures N. Mastboim, MeMed Diagnostics: Employee, Salary. K. Oved, MeMed Diagnostics: Board Member, Employee and Shareholder, Salary. T. Gottlieb, MeMed Diagnostics: Employee, Salary. A. Cohen, MeMed Diagnostics: Employee, Salary. R. Navon, MeMed Diagnostics: Employee, Salary. M. Paz, MeMed Diagnostics: Employee, Salary. E. Bamberger, MeMed Diagnostics: Employee, Salary. T. Friedman, MeMed Diagnostics: Employee, Salary. L. Etshtein, MeMed Diagnostics: Employee, Salary. O. Boico, MeMed Diagnostics: Employee, Salary. I. Potasman, MeMed Diagnostics: Holding stock options, Stock options. E. Eden, MeMed Diagnostics: Board Member, Employee and Shareholder, Salary. L. Shani, MeMed Diagnostics: Employee, Salary.

Background Diagnosing viral pneumonia in children is challenging. Chest radiographic imaging and clinical findings cannot reliably distinguish viral from bacterial pneumonia. Furthermore, pathogen-based diagnosis is limited by inaccessible site of infection and high asymptomatic detection rates. The objectives of this analysis were twofold: first, to establish pneumonia etiology by applying a rigorous expert panel process, and second, to evaluate whether a novel host-immune signature that integrates viral induced proteins TRAIL and IP-10 together with bacterial CRP, can accurately differentiate viral from bacterial pneumonia. Methods This analysis included 1025 febrile children enrolled in two multi-center clinical studies that evaluated the host-immune signature performance: ‘Curiosity’ study (Oved et al., PLoS One 2015) and ‘Pathfinder’ study (Srugo et al., Pediatrics 2017). Pneumonia etiology – viral or bacterial – was determined by a panel of 3 independent experts, after reviewing patients’ clinical, laboratory, microbiological, and radiological data. Only cases with majority panel assignment were included. The host-signature generated one of the three results: viral, equivocal or bacterial, based on predetermined cut-offs. Results A total of 709 children were eligible for analysis and had an expert panel etiology determination. Of them, 114 were diagnosed with pneumonia: 51 assigned viral and 63 assigned bacterial (Figure 1). The signature separated viral from bacterial pneumonia with a sensitivity of 94% (95% CI: 85%–99%) and specificity of 95% (85%–99%) with 14% equivocal test results. Out of the 51 children diagnosed with viral pneumonia by the expert panel, 40 (78%) were given antibiotics, and 43 (83%) underwent chest x-ray evaluation. The signature correctly classified 42 of these 51 viral children, indicating its potential to reduce antibiotic overuse rates by 4.4-fold (from 78% to 18%; P < 0.001) and chest x-ray examination by 4.8-fold (from 83% to 18%; P < 0.001). Conclusion The TRAIL/IP-10/CRP signature exhibits high accuracy for diagnosing viral pneumonia in children. The signature’s potential to safely decrease unnecessary antibiotics and chest radiographic imaging should be examined in future utility studies. Disclosures All authors: No reported disclosures.

The Bordetella pertussis polymerase chain reaction positivity rate changed after additional diphtheria-tetanus-acellular pertussis boosters in 2005 and 2008, 9.8%, 13.4%, 22% and 15.2% in 2010, 2011, 2012 and 2013, P < 0.001, respectively. New pulsed-field gel electrophoresis profiles were detected between 2009 and 2012. The proportion of pertactin-deficient isolates increased over time, 6.6% versus 7.1% versus 33.3% during 2005-2006, 2011-2012 and 2013-2014, P < 0.03, respectively.

BACKGROUND: Reliably distinguishing bacterial from viral infections is often challenging, leading to antibiotic misuse. A novel assay that integrates measurements of blood-borne host-proteins (tumor necrosis factor-related apoptosis-inducing ligand, interferon γ-induced protein-10, and C-reactive protein [CRP]) was developed to assist in differentiation between bacterial and viral disease. METHODS: We performed double-blind, multicenter assay evaluation using serum remnants collected at 5 pediatric emergency departments and 2 wards from children ≥3 months to ≤18 years without (n = 68) and with (n = 529) suspicion of acute infection. Infectious cohort inclusion criteria were fever ≥38°C and symptom duration ≤7 days. The reference standard diagnosis was based on predetermined criteria plus adjudication by experts blinded to assay results. Assay performers were blinded to the reference standard. Assay cutoffs were predefined. RESULTS: Of 529 potentially eligible patients with suspected acute infection, 100 did not fulfill infectious inclusion criteria and 68 had insufficient serum. The resulting cohort included 361 patients, with 239 viral, 68 bacterial, and 54 indeterminate reference standard diagnoses. The assay distinguished between bacterial and viral patients with 93.8% sensitivity (95% confidence interval: 87.8%–99.8%) and 89.8% specificity (85.6%–94.0%); 11.7% had an equivocal assay outcome. The assay outperformed CRP (cutoff 40 mg/L; sensitivity 88.2% [80.4%–96.1%], specificity 73.2% [67.6%–78.9%]) and procalcitonin testing (cutoff 0.5 ng/mL; sensitivity 63.1% [51.0%–75.1%], specificity 82.3% [77.1%–87.5%]). CONCLUSIONS: Double-blinded evaluation confirmed high assay performance in febrile children. Assay was significantly more accurate than CRP, procalcitonin, and routine laboratory parameters. Additional studies are warranted to support its potential to improve antimicrobial treatment decisions.

Acute bronchiolitis (AB) is caused primarily by respiratory syncytial virus (RSV). Recent laboratory tools have implicated a variety of other pathogens; however, their clinical relevance has not been clearly defined. The purpose of this study was to determine whether the etiological agents of AB affect its course. A multicenter prospective study was performed in previously healthy children

Pelvic inflammatory disease (PID) is a common disorder affecting sexually active adolescents. The Centers for Disease Control and Prevention (CDC) and European CDC report Chlamydia trachomatis as the most common sexually transmitted infection and one of the main etiological agents causing PID. C. trachomatis' and PID's high prevalence may be attributed to multiple factors including high-risk sexual behaviors, sensitive laboratory diagnostics (polymerase chain reaction), and the introduction of chlamydia screening programs. The pathogenesis of C. trachomatis infection is complex with recent data highlighting the role of toll-like receptor 2 and four in the mediation of the inflammatory cascade. The authors review the etiology of the disease, explore its pathogenesis, and discuss a variety of strategies that may be implemented to reduce the prevalence of C. trachomatis including: (a) behavioral risk reduction, (b) effective screening of asymptomatic females, (c) targeted male screening, (d) implementation of a sensitive, rapid, self-administered point-of-care testing, and (e) development of an effective vaccine.

Our aim was to evaluate the expression of Toll-like receptor-4 (TLR-4) and the level of interferon-gamma (IFN-γ) and interleukin-10 (IL-10) in young infants infected by Bordetella pertussis and B. parapertussis.Twenty-two infants under the age of 3.5 months with the clinical suspicion of pertussis were enrolled in the study. Nasopharyngeal secretions were obtained for laboratory testing, and blood samples were obtained for flow cytometry and cytokine level analysis.Six infants had positive PCR results for pertussis; the other 16 infants had infections attributable to another causal agent and were used as the control group. The mean fluorescence index, used as a measure of TLR-4 expression by monocytes, was significantly lower in infants with pertussis than in the control group infants (34.32 ± 18.58 vs. 63.14 ± 28, respectively; p = 0.041). The serum IFN-γ level was also significantly lower in infants with pertussis than in the control group patients (0.41 ± 0.58 vs. 1.36 ± 1.87, respectively; p = 0.04). No differences were found in the levels of IL-10.Based on these results, we suggest that TL4 expression by monocytes and serum INF-γ levels are lower in infants with positive PCR results for pertussis than in infants with a non-pertussis upper respiratory tract infection.

Background Identifying bacterial coinfection in influenza patients can be difficult as the symptoms of simple influenza vs. mixed infections are often similar, leading to antibiotic overuse. A new host-response assay (ImmunoXpert™) that integrates the levels of three proteins (TRAIL, IP-10, and CRP) was shown to exhibit high performance in distinguishing between bacterial and viral disease in two double-blind validation studies. Here we sought to evaluate its ability to differentiate between simple influenza and influenza with bacterial coinfection. Methods The study population included 653 febrile pediatric and adult patients prospectively recruited in the “Curiosity” study. Patient etiology (simple viral vs. mixed infection) was determined by unanimous expert adjudication based on comprehensive clinical, laboratory and radiological assessment. Influenza strains (A or B) were detected using multiplex PCR applied to nasal swabs (Seeplex-RV15). We compared the expert panel diagnosis with the assay that gives three possible outcomes: viral, bacterial (including viral with bacterial coinfection) or equivocal. An equivocal outcome does not provide diagnostic information and is observed in ~10% of cases. Results Out of 653 patients, 51 had positive influenza detection and unanimous expert diagnosis: 44 simple viral infections and seven influenza with bacterial coinfections (Figure 1). Antibiotics were prescribed to all seven cases of influenza with bacterial coinfection and to 20/44 cases adjudicated as simple viral infections, indicating an overuse rate of 45%. The assay correctly classified 40 of the 44 simple viral cases (out of the remaining four, two were assigned viral with bacterial coinfection, and two received equivocal outcomes) as well as five of the seven viral with bacterial coinfection cases (the remaining two received equivocal outcomes) supporting the assay’s potential to reduce antibiotic overuse 5-fold (from 45% to 4/44 = 9%, P < 0.001). Conclusion The host–response assay can differentiate between simple influenza and influenza patients with bacterial coinfection, with potential to reduce antibiotic overuse. Utility studies are warranted to demonstrate that the assay can safely assist physicians in correct management of influenza patients. Disclosures M. Paz, MeMed Diagnostics: Employee, Salary. K. Oved, MeMed Diagnostics: Board Member, Employee and Shareholder, Salary. T. Gottlieb, MeMed Diagnostics: Employee, Salary. A. Cohen, MeMed Diagnostics: Employee, Salary. R. Navon, MeMed Diagnostics: Employee, Salary. N. Mastboim, MeMed Diagnostics: Employee, Salary. E. Bamberger, MeMed Diagnostics: Employee, Salary. T. Friedman, MeMed Diagnostics: Employee, Salary. L. Etshtein, MeMed Diagnostics: Employee, Salary. O. Boico, MeMed Diagnostics: Employee, Salary. I. Potasman, MeMed Diagnostics: Holding stock options, Stock options. E. Eden, MeMed Diagnostics: Board Member, Employee and Shareholder, Salary. L. Shani, MeMed Diagnostics: Employee, Salary.

Background: Elevated IgE levels in patients with chronic urticaria have been noted previously, but the significance of these findings has not been appreciated. Objective: To measure the IgE levels in such patients and to examine the relationship between these levels and urticarial severity, autologous serum skin test, anti-thyroid antibodies and duration. Methods: Serum total IgE levels from 203 patients with chronic urticaria were measured and compared with nonatopic individuals. Additionally, patients were assessed for urticarial severity, the presence of autologous serum skin test and anti-thyroid antibodies. Results: Of the chronic urticaria patients, 47 (23.2%) were classified as mild, whereas 67 (33%) were classified as having moderate and 89 (43.8%) as having severe chronic urticaria. Total IgE levels were elevated, above 175 U/ml, in 69/203 (34%) of patients, compared with 7/81 (8.6%) of healthy controls (p < 0.001). A significant association between increased total IgE and chronic urticaria severity was found. Whereas 93% of patients with increased level of total IgE suffered from moderate-to-severe chronic urticaria, this was observed in only 69% of patients with normal IgE (p < 0.0001). Autologous serum skin test and anti-thyroid antibodies were positive in 59/163 (36%) and 28/189 (15%) patients, respectively. A significant association between increased total IgE levels and the presence of autologous serum skin test, anti-thyroid antibodies and urticarial duration lasting more than 25 months (p < 0.0001, p < 0.0001 and p = 0.021, respectively) was also detected. Conclusions: Total serum IgE levels are frequently elevated in patients with chronic urticaria and these are associated with disease severity and duration.

It is well-known that septic shock undermines immune homeostasis by inducing an initial intense systemic inflammatory response that is rapidly followed by a negative feedback of anti-inflammatory process. This secondary immunoparalysis state is characterized by decreased phagocytic cells, T cells, natural killer cells and B cells function and proinflammatory cytokine release. This persistence of immunoparalysis increased the risk for fatal outcome. In recent studies it was found that following the onset of septic shock, a relative increase in T regulatory cells number and suppressive function appears and makes them an important participant in the inhibition of immune responsiveness during sepsis. Consequently, a question emerging from these findings concerns the degree to which the manipulation of T regulatory cells might improve the outcome of patients with sepsis. Preliminary studies in animal models suggest that more work is needed to understand the conditions under which such a therapy may be effective.

ObjectiveEmotional intelligence (EI) is the individual's ability to perceive, understand and manage emotion and to understand and relate effectively to others. We examined the degree to which EI training may be associated with a change in EI among different medical personnel and patient satisfaction.Design, setting and participantsThe EI of 17 physicians and 10 nurses in paediatric ward was prospectively evaluated with Bar-On's EI at baseline and after 18 months. 11 physicians who did not undergo the intervention served as controls.InterventionsThe intervention consisted of a training programme comprising group discussions, simulations and case studies.Main outcomes and measuresPre-emotional quotient inventory (EQ-i) and post-EQ-i scores and patient satisfaction surveys of nurse and physicians pre-intervention and post-intervention were analysed.ResultsThe mean overall EI score of the study sample rose from 99.0±9.6 (both plus and minus mathematical operations standing for SD) at baseline to 105.4±10 (pConclusionAn EI intervention led to an overall increase in EI scores, with a significant improvement in patient satisfaction. These findings suggest important potential benefits for both staff and their patients.

We prospectively measured pertussis-specific antibodies 9-15 months after delivery in women immunized with tetanus, diphtheria, and acellular pertussis (Tdap) after the 20th week of their recent pregnancy. The Tdap-immunized women (n = 38) exhibited a decline in geometric mean concentrations between their peripartum and follow-up levels for immunoglobulin G to pertussis toxin (21.48 [95% confidence interval, 12.51-36.89] vs 11.72 [7.09-19.37] IU/mL];); filamentous hemagglutinin (185.95 [157.93-218.94] vs 140.33 IU/mL [113.46-173.57] IU/mL); and pertactin (171.52 [120.73-243.67] vs 83.74 [60.58-115.75] IU/mL) (all P < .001). For women immunized with Tdap during late pregnancy, pertussis-specific immunoglobulin G levels decreased significantly 9-15 months after delivery.

We describe an 8-month-old infant with infantile spasms treated with adrenocorticotropic hormone (ACTH) who presented with fatal Legionella pneumophila and Pneumocystis jirovecii infection. Emphasis is placed on the ensuing immunosuppression and infectious sequelae of ACTH therapy. Given that ACTH therapy may increase the risk of fatal infection, patients undergoing such treatment should be closely monitored, with particular attention paid to the functioning of the immune system.

Background Bacterial and viral infections are often clinically indistinguishable, particularly in upper respiratory tract infections (URTI), which leads to antibiotic misuse. A novel assay (ImmunoXpert™) that integrates measurements of three host-response proteins (TRAIL, IP-10, CRP) was recently developed to assist in differentiation between bacterial and viral etiologies. We evaluated the assay performance in URTI patients and compared it with standard laboratory measures. Methods We performed a sub-analysis of 464 patients with clinical suspicion of URTI enrolled in three previously conducted multi-center clinical studies that evaluated the assay performance in patients with acute infections: ‘Curiosity’ study (NCT01917461), ‘Opportunity’ study (NCT01931254), and ‘Pathfinder’ study (NCT01911143). Comparator method was predetermined criteria combined with expert panel adjudication, which was blinded to the test results. Diagnostic performance was evaluated by comparing test and comparator method outcomes. Results A unanimous panel adjudication was attained for 61 bacterial (13%) and 241 viral (52%) patients (162 patients (35%) had an indeterminate diagnosis). The assay distinguished between bacterial and viral infected patients with a sensitivity of 92% (95% CI: 82%- 98%) and specificity of 93% (88%-96%) with 11% equivocal test results. Overall the assay outperformed other routine laboratory tests (FIG 1), including: white blood cell count (WBC; cutoff 15,000 cells/µL, sensitivity 48% (35%-60%), P < 10-−6; specificity 85% (80%-90%), P < 0.05); CRP (cutoff 40 mg/L, sensitivity 82% (72%–92%), P = 0.16, specificity 79% (74%–84%), P < 10-4); Procalcitonin (PCT; cutoff 0.5 ng/mL, sensitivity 22% (11%–32%), P < 10–14, specificity 80% (74%–85%), P < 0.001); absolute neutrophil count (ANC; cutoff 10,000 cells/µL, sensitivity 58% (45%–71%), P < 10-−4, specificity 94% (91%–97%), P = 0.7). Conclusion The novel assay demonstrated superior performance compared with routine laboratory tests (WBC, ANC) and biomarkers (CRP, PCT), in distinguishing bacterial from viral etiologies in patients with URTI. It has the potential to help clinicians avoid missing bacterial infections or prescribing unwarranted antibiotics for viral URTIs. Disclosures K. Oved, MeMed Diagnostics: Board Member, Employee and Shareholder, Salary E. Eden, MeMed Diagnostics: Board Member, Employee and Shareholder, Salary T. Gottlieb, MeMed Diagnostics: Employee, Salary R. Navon, MeMed Diagnostics: Employee, Salary A. Cohen, MeMed Diagnostics: Employee, Salary O. Boico, MeMed Diagnostics: Employee, Salary M. Paz, MeMed Diagnostics: Employee, Salary L. Etshtein, MeMed Diagnostics: Employee, Salary G. Kronenfeld, MeMed Diagnostics: Employee, Salary T. Friedman, MeMed Diagnostics: Employee, Salary E. Bamberger, MeMed Diagnostics: Employee, Salary I. Chistyakov, MeMed Diagnostics: Consultant, Consulting fee I. Potasman, MeMed Diagnostics: Holding stock options, stock options

Background: Despite the disabling nature of chronic urticaria (CU), little is known about the disease's duration or the efficacy of adopting aggressive therapeutic regimens such as cyclosporine A. Objectives: The aim of this study was to evaluate whether parameters such as angioedema, autologous serum test, anti-thyroid antibodies, and total IgE could predict both CU duration and severity. Patients and methods: One hundred and thirty-nine patients suffering from CU were prospectively followed over a 5-year period for disease duration, severity and the presence of angioedema. Also investigated was the association between these clinical parameters and the subsequent detection of autologous serum test, anti-thyroid antibodies, and total IgE. Results: CU lasted over 1 year in more than 70% of cases and in 14% it still existed after 5 years. Angioedema co-existed or appeared during the course of CU in 40% of patients and was associated with disease duration. Autologous serum test and anti-thyroid antibodies were found positive in 28 and 12% of patients, respectively, compared to none of normal individuals, P = 0.001. CU duration was associated with the presence of both autologous serum test and anti-thyroid antibodies; however, autologous serum test and not anti-thyroid antibodies was found in association with CU severity. Conclusion: We demonstrate for the first time that CU duration is associated with clinical parameters such as severity and angioedema, and with laboratory parameters such as autologous serum test and anti-thyroid antibodies. The ability to predict CU duration may facilitate decisions regarding the possible early initiation of cyclosporine A as a means by which to reduce disease severity and duration.

The development of systemic lupus erythematosus (SLE) vasculitis is of prognostic value. The earlier the vasculitis is treated, the better the prognosis for SLE. Cutaneous vasculitis is common in SLE, whereas visceral vasculitis is rare. Skin SLE vasculitis is successfully treated with antimalarials, but its discontinuation may result in an SLE flare even among patients in remission. When visceral SLE vasculitis is encountered, or when a disease state is perceived to be life-threatening, a more aggressive therapy is warranted. A combination of medications, plasmapheresis, and intravenous immunoglobulin treatment, along with high-dose steroids and cytotoxic drugs, are typically employed in the treatment of severe SLE vasculitis. Finally, patients with SLE vasculitis may benefit from a number of autoimmune disease therapies currently under investigation, such as switching cytokine responses from Th1 to Th2, and the manipulation of toll-like receptors, chemokines, and FcR receptors. Specific B-cell therapies (eg, anti-Blys, B-cell depletion) may also emerge as potential treatments for SLE vasculitis.