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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

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.

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 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.

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.

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: 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: 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 Centers for Disease Control and Prevention recommend Tdap immunization during pregnancy, preferably at 27-36 weeks.To ascertain whether there is a preferential period of maternal Tdap immunization during pregnancy that provides the highest concentration of pertussis-specific antibodies to the newborn.This prospective study measured pertussis-specific antibodies in paired maternal-cord sera of women immunized with Tdap after the 20th week of their pregnancy (n=61).The geometric mean concentrations (GMCs) of Immunoglobulin G (IgG) to pertussis toxin (PT) were higher in the newborns' cord sera when women were immunized at 27-30(+6) weeks (n=21) compared with 31-36 weeks (n=30) and36 weeks (n=7), 46.04 international units/milliliter (IU/mL) (95% CI, 24.29-87.30) vs. 8.69IU/mL (95% CI, 3.66-20.63) and 21.12IU/mL (95% CI, 7.93-56.22), p0.02, respectively. The umbilical cord GMCs of IgG to filamentous hemagglutinin (FHA) were higher in the newborns' cord sera when women were immunized at 27-30(+6) weeks compared with 31-36 weeks and36 weeks, 225.86IU/mL (95% CI, 182.34-279.76) vs. 178.31IU/mL (95% CI, 134.59-237.03) and 138.03IU/mL (95% CI, 97.61-195.16), p0.02, respectively.Immunization of pregnant women with Tdap between 27-30(+6) weeks was associated with the highest umbilical cord GMCs of IgG to PT and FHA compared with immunization beyond 31 weeks gestation. Further research should be conducted to reaffirm these finding in order to promote an optimal pertussis controlling policy.

The most common infectious causes of genital ulcers are herpes simplex virus and syphilis. However, mixed infections can occur and genital ulcer may increase the risk of acquiring human immunodeficiency virus. Although the history and physical examination can narrow the differential diagnosis, there is a need for initial routine laboratory testing for the most common pathogens that includes: for syphilis: serologic screening and dark field examination of the lesion; for herpes simplex virus: serology, vial culture and/or polymerase chain reaction. Human immunodeficiency testing is mandatory. Recently, some clinical laboratories adapted the reverse screening algorithm for syphilis (initial treponemal test, and, if positive, followed by non-treponemal test) that may potentially lead to overtreatment. Early and prompt therapy may decrease the risk of transmission of the infectious agent to others. This article reviews the infectious pathogens causing genital ulcers, their unique clinical manifestation, diagnosis and treatment.

We examined the prevalence of Chlamydia trachomatis infection in Israeli female soldiers. The prevalence was 3.2% among soldiers seeking medical care; rural residence was identified as a significant risk factor. Nevertheless, given the study design, recommending broad-scale screening of Israeli female soldiers may be premature.2

In Israel, there have been increasing reports of Bordetella pertussis infection among adolescents and adults, but the peak incidence and highest mortality occur among infants. The authors report four cases involving the likely transmission of pertussis from parents to their offspring in two hospitals in Israel. The adoption of proper infection control measures and targeted screening of parents may reduce the potential risk for such transmission.

To determine the rate of pertussis in infants aged1 year hospitalized at the pediatric intensive care unit (PICU) with lower respiratory tract infection (LRTI) and to characterize the clinical aspects of these patients.Infants12 months hospitalized with LRTI in the PICU were identified retrospectively. Demographic, clinical and laboratory data were obtained. Stored nasopharyngeal washes (NPW) were tested by polymerase chain reaction (PCR) for the pertussis toxin gene (ptxA) and insertion element IS481 sequences.Eleven of seventy-four (15%) NPW were positive for pertussis, none of them was clinically suspected. Of the positive patients, 82% suffered from paroxysmal cough vs. 32% of the negative patients and from prolonged cough, 45.5% vs. 8%, respectively (P0.01). Thirty (41%) patients needed mechanical ventilation with no differences between positive and negative pertussis patients. Infiltrates in x-rays were more common among pertussis negative than among pertussis positive patients, 29% vs. 0% (P=0.05).Lower respiratory tract infections caused by pertussis are a more frequent cause of admission to the PICU than generally recognized. Patient's history with paroxysmal cough suggests the possibility of pertussis and the lack of whooping cough does not rule out pertussis. Pediatricians should be aware of the limitations of their diagnostic tools when ruling out pertussis especially in infants with a diagnosis of bronchiolitis. Using new diagnostic methods add considerably to the sensitivity of pertussis diagnosis in PICU and PCR techniques should be used routinely, at least in a PICU setting.

SummaryIn this study, we compared the rate of spontaneous apoptosis of B cells from umbilical cord blood with adult B cells and assessed the role of Bcl-2, CD5, interleukin (IL)-4 and B cell-activating factor in B cell spontaneous apoptosis. We found that spontaneous apoptosis of cultured B cells, as assessed by utilizing annexin-V binding, was significantly higher in cord blood than in healthy adult individuals (77·5; 95 CI, 73·5–81·5 versus 59·2; 95 CI, 54–64, respectively, P < 0·0001) and further confirmed by 4′ 6-diamidino-2-phenylindole, dihydrochloride (DAPI) staining. Whereas the expression of B cell-activating factor from the tumour necrosis factor family (BAFF) receptor mRNA was similar in B cells from adults and cord blood, we detected lower levels of circulating BAFF in the serum of cord blood (0·68 ± 0·13 ng versus 1·83 ± 0·54 ng, P = 0·01). The latter may explain, in part, our observation of lower levels of mean fluorescence intensity of Bcl-2 in cord B cells compared with adults (1·6 ± 0·9 versus 2·85 ± 1·3, P = 0·033). CD19+ CD5+ B cells from cord blood underwent a lower rate of apoptosis in comparison to CD19+ CD5– B cells (25·1 ± 9·3%versus 58·5 ± 12·5%, P < 0·0001). This pattern of sensitivity was comparable in adult blood (15 ± 5·5%versus 22·7 ± 9·3%, P = 0·01). Nevertheless, the rate of apoptosis was higher in CD19+ CD5+ from cord blood compared to CD19+ CD5+ from adults (25·1 ± 9·3%versus 15 ± 5·5%, P = 0·0013). The addition of rIL-4 (10 u/ml) to cultured cells decreased B cell apoptosis in a similar fashion in both cord and adults blood. This rescue was strengthened when BAFF (100 µg/ml) was further added. Thus, alterations in Bcl-2 or serum BAFF level may explain the increased rate of cord blood B cell apoptosis.

The Israel Ministry of Health's epidemiology department reported a record number of 1564 new pertussis cases in 2004. This brings the incidence rate to 23 per 100,000 population, indicating a marked increase in the prevalence of pertussis, from 1-3/100,000 in 1998, 9 in 2001, to 14 in 2003. The rate of atypical pertussis presentations in vaccinated patients, the decline in pertussis immunity post-vaccination, and the decreased awareness of potential infections in the adult population make the diagnosis of pertussis difficult and contribute to the rising incidence. In this article we review the current literature in order to increase awareness of the occurrence of pertussis in children as well as adults, discuss the laboratory diagnostic methods being used, and report the currently recommended means of treating the disease.

Whereas the diagnosis of classical pertussis has traditionally been based on clinical criteria, increasing numbers of atypical presentations suggest the need for an extensive laboratory-based approach.To assess the relative efficacy of clinical and laboratory methods in the diagnosis of Bordetella pertussis by patient age and immunization status.We compared the clinical and laboratory diagnosis of B. pertussis in 87 pre-vaccinated, 78 recently vaccinated, and 75 post-vaccinated children with suspected pertussis. Serum and nasopharyngeal swabs were obtained for serology, culture and polymerase chain reaction.PCR and culture identified 41% and 7% of patients with B. pertussis, respectively (P0.001). All positive cultures were PCR-positive. Positive PCR was less common among those recently vaccinated than among those in the pre- (P0.001) and post-vaccinated groups (P0.05). Positive culture was more common among those pre-vaccinated than among those recently vaccinated (P0.01). Positive tests for immunoglobulin M and A were more common among the post-vaccinated than the pre- and recently vaccinated (P0.001), respectively. Logistic regression analyses revealed that clinical criteria have no significant association with infection in recently and post-vaccinated children. Among the pre-vaccinated children, whoop and cough duration were associated with a positive PCR (odds ratio 7.66 and 0.5, P0.001). Seventy-six percent of pre-vaccinated, 39% of recently vaccinated and 40% of post-vaccinated children with positive PCR did not meet the U.S. Centers for Disease Control diagnostic criteria for B. pertussis.PCR is a useful tool for pertussis diagnosis, particularly in pre-vaccinated infants. The yield of culture and serology is limited, especially among pre- and recently vaccinated children. In pre-vaccinated infants with whoop and less than 2 weeks of cough, PCR testing should be implemented promptly.

We report 4 cases involving the likely transmission of pertussis from parents to newborns in a hospital setting. The adoption of proper infection control measures and targeted screening of parents may reduce the potential for such transmission.

Although the current literature attributes most cases of hematospermia to an infectious agent, identification of the specific pathogens involved has been limited.To determine the prevalence of different pathogens in patients presenting with hematospermia to our sexually transmitted disease clinic.Between January 1999 and January 2000, 16 patients presented to our STD clinic with hematospermia after other noninfectious pathologies had been excluded by a referring physician. After obtaining informed consent, subjects completed a questionnaire addressing symptoms and sexual behavior. First-void urine samples, as well as genitourinary and serum specimens were tested for Chlamydia trachomatis, Ureaplasma urealyticum and herpes simplex virus. Standard bacterial cultures were also performed.Laboratory testing detected a pathogen in 12 of the 16 males presenting with hematospermia. The sexually transmitted pathogens detected were herpes simplex virus in 5 patients (42%), Chlamydia trachomatis in 4 (33%), Enterococcus fecalis in 2 (17%), and Ureaplasma urealyticum in 1 (8%). In all cases in which a pathogen was identified, the appropriate antimicrobial agent was administered. Symptoms resolved for each patient following antimicrobial therapy. During a 1 year follow-up, all 12 patients remained free of disease.Recent advances in microbiologic diagnostic techniques have facilitated the detection of pathogens in patients with hematospermia, thereby enhancing the efficacy of treatment.

Summary Background Matrix metalloproteinase (MMP)-9 is produced by many inflammatory cells such as macrophages, neutrophils, mast cells, eosinophils and T lymphocytes. Activated T cells are capable, through cell–cell contact, of inducing MMP-9 expression in human mast cells. Objective To investigate the activation status of peripheral CD4+ T cells and the level of MMP-9 in the plasma of patients with chronic urticaria (CU), and whether MMP-9 levels are in association with CU severity. Methods Study subjects included 29 patients with CU and 30 healthy control subjects. At the time of assessment, patients were divided into subgroups according to urticarial severity. Plasma levels of total MMP-9 (free pro-MMP-9 and free MMP-9) were determined by ELISA. CD4+ lymphocytes were positively selected with magnetic microbeads. After 48 h of activation, CD4+ T cells were assayed for both nuclear factor-kappaB (NF-κB) expression and proliferation. Results Plasma levels of MMP-9 were found to be significantly higher in 29 CU patients compared with 18 healthy controls (186±174 vs. 31±21 ng/mL, P

We report the result of a pilot study of low-dose tacrolimus for the treatment of patients with severe chronic idiopathic urticaria (CIU). Nineteen patients with severe CIU were treated with tacrolimus for 12 weeks. Two patients dropped out after 1 week of treatment because of side effects. Following 3 months of treatment, 12 of 17 patients (70.5%) had a clinical response to tacrolimus. In 9 patients, the urticaria had been improved significantly (urticarial score 0-1), enabling them to discontinue antihistamines and, in the case of two patients, corticosteroids. The remaining 3 patients had moderate improvement (urticarial score 2). Three months after the discontinuation of tacrolimus, 3 of 10 responders had a complete resolution of their urticaria (urticarial score 0), 3 had mild deterioration (urticarial score 1-2) controllable by antihistamines alone, and 4 patients had a full relapse (urticarial score 3). Our preliminary results suggest tacrolimus as a treatment option for patients with severe CIU.

This review presents an update on the use of probiotics and prebiotics in children. We review the normal flora, and present the possible mechanisms by which the probiotic bacteria exert their beneficial effects. We present data from multiple studies suggesting that probiotics are effective for the treatment and prevention of acute non-bloody infections diarrhea, antibiotic associated diarrhea as well as the prevention and treatment of atopic dermatitis and other allergic conditions. The safety and future directions of pro- and prebiotic treatments are discussed.

Eighty-two isolates of Bordetella pertussis analyzed by pulsed-field gel electrophoresis from the epidemic years, 2007 to 2008, revealed 4 strains with 2 closely related isolates accounting for 95% of the circulating strains. The most common Israeli strain has the same pulsed-field gel electrophoresis cluster as the dominant European BpSR11 strain (pulsed-field gel electrophoresis cluster IVβ) identified in the 1999 to 2004 EU Pertstrain II project.

Bacterial and viral infections are often clinically indistinguishable, leading to inappropriate patient management and antibiotic misuse. Bacterial-induced host proteins such as procalcitonin, C-reactive protein (CRP), and Interleukin-6, are routinely used to support diagnosis of infection. However, their performance is negatively affected by inter-patient variability, including time from symptom onset, clinical syndrome, and pathogens. Our aim was to identify novel viral-induced host proteins that can complement bacterial-induced proteins to increase diagnostic accuracy. Initially, we conducted a bioinformatic screen to identify putative circulating host immune response proteins. The resulting 600 candidates were then quantitatively screened for diagnostic potential using blood samples from 1002 prospectively recruited patients with suspected acute infectious disease and controls with no apparent infection. For each patient, three independent physicians assigned a diagnosis based on comprehensive clinical and laboratory investigation including PCR for 21 pathogens yielding 319 bacterial, 334 viral, 112 control and 98 indeterminate diagnoses; 139 patients were excluded based on predetermined criteria. The best performing host-protein was TNF-related apoptosis-inducing ligand (TRAIL) (area under the curve [AUC] of 0.89; 95% confidence interval [CI], 0.86 to 0.91), which was consistently up-regulated in viral infected patients. We further developed a multi-protein signature using logistic-regression on half of the patients and validated it on the remaining half. The signature with the highest precision included both viral- and bacterial-induced proteins: TRAIL, Interferon gamma-induced protein-10, and CRP (AUC of 0.94; 95% CI, 0.92 to 0.96). The signature was superior to any of the individual proteins (P

Legionnaire disease is a rare cause of community-acquired pneumonia in children and an exceedingly rare diagnosis in infants and neonates, with only few reported cases. We describe a case of fatal Legionnaire disease diagnosed by culture and polymerase chain reaction method from sputum and lung biopsy specimens, and emphasize the importance of considering this rare entity in cases of severe neonatal pneumonia.

Inflammatory processes affecting nasal and bronchial mucosa are similar in nature. The purpose of this study was to examine whether children with perennial allergic rhinitis, without underlying asthma, have impaired pulmonary function. We also investigated whether nasal corticosteroids and loratidine would improve the pulmonary function tests of those children with impaired lung function. Fifty subjects with moderate/severe persistent allergic rhinitis due to exclusively dust mite sensitization and no past medical history suggestive of asthma were assessed. The control group consisted of 26 matched healthy subjects. Subjects with airway obstruction, as detected by forced expiratory volume/1 s (FEV1) or forced expiratory flow from 25/% to 75% (FEF(25-75)) values80% of those predicted, were treated with loratidine, once a day for 10 days, and daily nasal budesonide for 3 months. We found that 11 of 50 patients (22%) with perennial allergic rhinitis had impaired pulmonary function (FEF(25-75) values80%), compared to 1/26 (3.8%) of the control group (por = 0.05). Reversibility was observed in 9/11 (81.8%), mean 24.7% +/- 10.3%. Within 3 months of treatment, 7/10 had FEF(25-75)80% of their predicted values as well as significant improvements in their FEV1 (p = 0.04), and FEV1/FVC (p = 0.04). We conclude that a substantial proportion of children with perennial allergic rhinitis have diminished FEF (25-75) values and reversible airway obstruction. Nasal corticosteroids improve the pulmonary function tests of these children with impaired lung function.

Despite high vaccination coverage, over the last fifteen years there has been a worldwide resurgence of B. pertussis infection. While classical pertussis in the prevaccine era was primarily a childhood disease, today with widespread vaccination, there has been a shift in the incidence of disease to adolescents and adults. Centers of Disease Control and Prevention (CDC) data from 2004 reveal a nearly 19-fold increase in the number of cases in individuals 10–19 years and a 16-fold increase in persons over 20 years. Indeed adolescent and adults play a significant role in the transmission of pertussis to neonates and infants who are vulnerable to substantial morbidity and mortality from pertussis infection. Several explanations have been proposed to explain the increasing incidence of disease, with waning immunity after natural infection or immunization being widely cited as a significant factor. Improving molecular biology diagnostic techniques, namely PCR assays, also accounts for the increasing laboratory diagnosis of pertussis. Expanding vaccination strategies including universal immunization of adolescents, targeted immunization of adults, and in particular, healthcare workers, childcare providers and parents of newborns, will likely improve pertussis control. With pertussis continuing to pose a serious threat to infants, and greatly affecting adolescents and adults, there remains a need to: (a) increase the awareness of physicians as to the growing pertussis problem, (b) standardize diagnostic techniques, and (c) implement various new vaccine strategies to enhance its control.