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Background There is scarce information focused on the effect of weather conditions and air pollution on specific acute viral respiratory infections, such as rhinovirus (RV), with a wide clinical spectrum of severity. Objective The aim of this study was to analyze the association between episodes of severe respiratory tract infection by RV and air pollutant concentrations (NOx and SO2) in the reference area of a pediatric university hospital. Methods An analysis of temporal series of daily values of NOx and SO2, weather variables, circulating pollen and mold spores, and daily number of admissions in the pediatric intensive care unit (PICU) with severe respiratory RV infection (RVi) in children between 6 months and 18 years was performed. Lagged variables for 0-5 days were considered. The study spanned from 2010 to 2018. Patients with comorbidities were excluded. Results One hundred and fifty patients were admitted to the PICU. Median age was 19 months old (interquartile range [IQR]: 11-47). No relationship between RV-PICU admissions and temperature, relative humidity, cumulative rainfall, or wind speed was found. Several logistic regression models with one pollutant and two pollutants were constructed but the best model was that which included average daily NOx concentrations. Average daily NOx concentrations were related with the presence of PICU admissions 3 days later (odds ratio per IQR-unit increase: 1.64, 95% confidence interval: 1.20-2.25)). Conclusions This study has shown a positive correlation between NOx concentrations at Lag 3 and children's PICU admissions with severe RV respiratory infection. Air pollutant data should be taken into consideration when we try to understand the severity of RVis.

Background: We aimed to determine the impact of utilizing a rapid panel test of respiratory viral and atypical bacteria (FilmArray (R) Respiratory Panel, FA RP) on etiological diagnosis of acute lower respiratory infection (ALRI) and antimicrobial stewardship in critical care pediatric patients. Methods: Prospective cohort study of patients aged < 18 years with clinical diagnosis of ALRI that were admitted to the Pediatric Intensive Care Unit (PICU) of Hospital Sant Joan de Deu (Barcelona, Spain) during December 2015-February 2017. Patients were diagnosed by FA RP and by a bundle of routine microbiological assays. Results: ALRI viral and bacterial etiology was confirmed by a composite reference standard of routine microbiological assays in 72 (55.4%) and 15 (11.5%) respiratory samples, respectively, that were collected from 130 children (median age, 3.5 months, IQR 1.1-14.8 months; 54.6% male). Comparatively, FA RP use increased etiological confirmation of ALRI in up to 123 (94.6%) samples (p < 0.001) but only determined a bacterial origin in 2 (1.5%). Availability of diagnostic results before patient discharge from the PICU rose from 65.4 to 38.5% (p < 0.001). Use of the new panel test directly influenced antimicrobial stewardship in 11 (8.4%) episodes, leading to discontinuation of antiviral drugs (n= 5), administration of targeted antibiotics (n= 3), antiviral therapy start (n= 2) and both targeted antibiotic administration and discontinuation of antiviral drugs (n =1). Conclusion: FA RP contributed to improve etiological diagnosis of ALRI in a timely manner while enhancing a more rational use of antimicrobial drugs in critical care pediatric patients. (C) 2020 Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinica. Published by Elsevier Espana, S.L.U. All rights reserved.

Aim To develop a quantitative predictive scoring model for the early recognition and assessment of paediatric sepsis. Methods Prospective observational study including emergency department and in-hospital febrile patients under 18 years. Sepsis diagnose (Goldstein 2005 definitions) was the main outcome. Variables associated with the outcome were included in a multivariable analysis. Cut-off points, odds ratio and coefficients for the variables kept after the multivariable analysis were identified. The score was obtained from the coefficients, The AUC was obtained from ROC-analysis, and internal validation was performed using k-fold cross-validation. Results The analysis included 210 patients. 45 variables were evaluated and the bivariate analysis identified 24 variables associated with the outcome. After the multivariable regression, 11 variables were kept and the score was obtained. The model yielded an excellent AUC of 0.886 (95% CI 0.845-0.927), p < 0.001 for sepsis recognition. With a cut-off value of 5 for the score, we obtained a sensitivity of 98%, specificity of 76.7%, positive predictive value of 87.9% and negative predictive value of 93.3%. Conclusion The proposed scoring model for paediatric sepsis showed adequate discriminatory capacity and sufficient accuracy, which is of great clinical significance in detecting sepsis early and predicting its severity. Nevertheless external validation is needed before clinical use.

Background: Bronchiolitis is the most common viral infection of the lower respiratory tract in infants under 2 years of age. The aim of this study was to analyze and compare the seasonal bronchiolitis peaks before and during the SARS-CoV-2 pandemic. Methods: Descriptive, prospective, and observational study. Patients with severe bronchiolitis admitted to the Pediatric Intensive Care Unit (PICU) of a referral tertiary hospital between September 2010 and June 2021 were included. Demographic data were collected. Viral laboratory-confirmation was carried out. Each season was analyzed and compared. The daily average temperature was collected. Results: 1116 patients were recruited, 58.2% of them males. The median age was 49 days. Respiratory syncytial virus (RSV) was isolated in 782 cases (70.1%). In April 2021, the first and only case of bronchiolitis caused by SARS-CoV-2 was identified. The pre- and post-pandemic periods were compared. There were statistically significant differences regarding: age, 47 vs. 73 days (p = 0.006), PICU and hospital length of stay (p = 0.024 and p = 0.001, respectively), and etiology (p = 0.031). The peak for bronchiolitis in 2020 was non-existent before week 52. A delayed peak was seen around week 26/2021. The mean temperature during the epidemic peak was 10 degrees C for the years of the last decade and is 23 degrees C for the present season. Conclusion: The COVID-19 pandemic outbreak has led to a clearly observable epidemiological change regarding acute bronchiolitis, which should be studied in detail. The influence of the environmental temperature does not seem to determine the viral circulation.

Aetiological diagnosis of gastrointestinal infections is challenging since a wide range of bacteria, parasites and viruses can be causal agents and derived clinical manifestations appear quite similar. Our aim was to evaluate contribution of the novel QIAstat-DxGastrointestinal Panel (GIP) to aetiological diagnosis of gastrointestinal infections and rational antimicrobial prescription in a reference paediatric hospital. Evaluation included comparison of diagnostic yield and agreement of results of QIAstat-Dx GIP and conventional microbiological methods. Parallel testing was performed on stool samples collected prospectively from children admitted to Sant Joan de Deu Barcelona Hospital (Spain) during the period February-March 2019. Influence of the panel test use on antimicrobial prescription was assessed using a pre-post study design. Eighty-six (68.8%) out of 125 specimens were positive by QIAstat-Dx GIP versus 44 (35.2%) positive by a composite of conventional methods (p

BACKGROUND: Susceptibility of children and adults to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and persistence of antibody response to the virus after infection resolution remain poorly understood, despite their significant public health implications. METHODS: A prospective cross-sectional seroprevalence study with volunteer families that included at least 1 first-reported adult case positive by SARS-CoV-2 by polymerase chain reaction (PCR) and at least 1 child aged

PURPOSE: The purpose of this study was to characterize the nasopharyngeal microbiota of infants with possible and confirmed pertussis compared to healthy controls. METHODS: This prospective study included all infants

We aimed to assess the duration of nasopharyngeal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA persistence in adults self-confined at home after acute infection; and to identify the associations of SARS-CoV-2 persistence with respiratory virus co-detection and infection transmission. A cross-sectional intra-household study was conducted in metropolitan Barcelona (Spain) during the time period of April to June 2020. Every adult who was the first family member reported as SARS-CoV-2-positive by reverse transcription polymerase chain reaction (RT-PCR) as well as their household child contacts had nasopharyngeal swabs tested by a targeted SARS-CoV-2 RT-PCR and a multiplex viral respiratory panel after a 15 day minimum time lag. Four-hundred and four households (404 adults and 708 children) were enrolled. SARS-CoV-2 RNA was detected in 137 (33.9%) adults and 84 (11.9%) children. Rhinovirus/Enterovirus (RV/EV) was commonly found (83.3%) in co-infection with SARS-CoV-2 in adults. The mean duration of SARS-CoV-2 RNA presence in adults' nasopharynx was 52 days (range 26-83 days). The persistence of SARS-CoV-2 was significantly associated with RV/EV co-infection (adjusted odds ratio (aOR) 9.31; 95% CI 2.57-33.80) and SARS-CoV-2 detection in child contacts (aOR 2.08; 95% CI 1.24-3.51). Prolonged nasopharyngeal SARS-CoV-2 RNA persistence beyond the acute infection phase was frequent in adults quarantined at home during the first epidemic wave; which was associated with RV/EV co-infection and could enhance intra-household infection transmission.

OBJECTIVE: To validate and implement an optimized screening method for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA combining use of self-collected raw saliva samples, single-step heat-treated virus inactivation and RNA extraction, and direct RT-qPCR. METHODS: This was a three-phase study conducted in Barcelona (Spain) during June to October, 2020. The three phases were (1) analytical validation against standard RT-qPCR in saliva samples; (2) diagnostic validation against standard RT-qPCR using paired saliva-nasopharyngeal samples obtained from asymptomatic teenagers and adults in a sports academy; and (3) pilot screening of asymptomatic health workers in a tertiary hospital. RESULTS: In phase 1, the detection yield of the new method was comparable to that of standard RT-qPCR. In phase 2, the diagnostic sensitivity and specificity values in 303 self-collected saliva samples were 95.7% (95% confidence interval 79.0-99.2%) and 100.0% (95% confidence interval 98.6-100.0%), respectively. In phase 3, only 17 (0.6%) of the saliva samples self-collected by 2709 participants without supervision were invalid. The rapid analytical workflow with the new method (up to 384 batched samples could be processed in less than 2 hours) yielded 24 (0.9%) positive results in the remaining 2692 saliva samples. Paired nasopharyngeal specimens were all positive by standard RT-qPCR. CONCLUSIONS: Direct RT-qPCR on self-collected raw saliva is a simple, rapid, and accurate method with potential to be scaled up for enhanced SARS-CoV-2 community-wide screening.

Infection by rhinovirus (RV) and enterovirus (EV) in children ranges from asymptomatic infection to severe lower respiratory tract infection (LRTI). This cohort study evaluates the clinical impact of RV/EV species, alone or in codetection with other viruses, in young children with severe LRTI. Seventy-one patients aged less than 5 years and admitted to the Paediatric Intensive Care Unit (PICU) of a reference children's hospital with RV or EV (RV/EV) LRTI were prospectively included from 1/2018 to 3/2020. A commercial PCR assay for multiple respiratory pathogens was performed in respiratory specimens. In 22/71, RV/EV + respiratory syncytial virus (RSV) was found, and 18/71 had RV/EV + multiple viral detections. Patients with single RV/EV detection required invasive mechanical ventilation (IMV) as frequently as those with RSV codetection, whereas none of those with multiple viral codetections required IMV. Species were determined in 60 samples, 58 being RV. No EV-A, EV-C, or EV-D68 were detected. RV-B and EV-B were only found in patients with other respiratory virus codetections. There were not any associations between RV/EV species and severity outcomes. To conclude, RV/EV detection alone was observed in young children with severe disease, while multiple viral codetections may result in reduced clinical severity. Differences in pathogenicity between RV and EV species could not be drawn.

The elevation of neopterin in cerebrospinal fluid (CSF) has been reported in several neuroinflammatory disorders. However, it is not expected that neopterin alone can discriminate among different neuroinflammatory etiologies. We conducted an observational retrospective and case-control study to analyze the CSF biomarkers neopterin, total proteins, and leukocytes in a large cohort of pediatric patients with neuroinflammatory disorders. CSF samples from 277 subjects were included and classified into four groups: Viral meningoencephalitis, bacterial meningitis, acquired immune-mediated disorders, and patients with no-immune diseases (control group). CSF neopterin was analyzed with high-performance liquid chromatography. Microbiological diagnosis included bacterial CSF cultures and several specific real-time polymerase chain reactions. Molecular testing for multiple respiratory pathogens was also included. Antibodies against neuronal and glial proteins were tested. Canonical discriminant analysis of the three biomarkers was conducted to establish the best discriminant functions for the classification of the different clinical groups. Model validation was done by biomarker analyses in a new cohort of 95 pediatric patients. CSF neopterin displayed the highest values in the viral and bacterial infection groups. By applying canonical discriminant analysis, it was possible to classify the patients into the different groups. Validation analyses displayed good results for neuropediatric patients with no-immune diseases and for viral meningitis patients, followed by the other groups. This study provides initial evidence of a more efficient approach to promote the timely classification of patients with viral and bacterial infections and acquired autoimmune disorders. Through canonical equations, we have validated a new tool that aids in the early and differential diagnosis of these neuroinflammatory conditions.

AIM: Our aim was to determine the effectiveness and safety of a procalcitonin-guided protocol to decrease antibiotic use in infants with severe bronchiolitis. METHODS: This prospective, observational study was conducted at the Hospital Sant Joan de Déu from 2010 to 2017. Patients under the age of one were included if they were diagnosed with bronchiolitis, had a suspected bacterial infection and were admitted to the paediatric intensive care unit. A procalcitonin-guided protocol was established in 2014, and two cohorts were compared before and after implementation: 340 in 2010-2014 and 366 in 2015-2017. RESULTS: We recruited 706 patients (58.6% male) with a median age of 47 days and an interquartile range of 25.0-100.2. The rate for antibiotic use was 79.9%, and this differed before and after implementation (88.2% vs 72.1%, P = .003). Antibiotic stewardship and withdrawal decisions were higher after implementation (22.3% vs 36.4%, P = .005). The length of antibiotic treatment was also different between the two periods (8.65 ± 4.8 days vs 5.05 ± 3.18 days, P = .023). No adverse outcomes were observed due to the implementation of the protocol. CONCLUSION: The implementation of a procalcitonin-guided protocol seems to lead to a safe and general decrease in antibiotic use in paediatric patients with severe bronchiolitis.

Early diagnosis of sepsis and its severity stratification at admission is critical to improve patient outcomes and to ensure the optimal use of health care resources. In order to assess the diagnostic potential of mid-regional pro-adrenomedullin (MR-proADM) in septic paediatric patients in comparison with procalcitonin (PCT), and to evaluate the usefulness of a single early determination of MR-proADM as a stratification and severity prediction tool, a prospective observational study was conducted. Seventy-three paediatric patients with a suspicion of sepsis were included. A single blood test was carried out at initial time to analyse infection biomarkers. PCT values were significantly higher in septic patients in comparison with non-septic patients (p = 0.03) with an AUC of 0.748 (p = 0.003). Levels of MR-proADM significantly increased in patients with severe sepsis (p = 0.048), with an AUC of 0.729 (p = 0.013). MR-proADM showed a positive correlation with pSOFA, PRISM III, and PELOD-2 severity scores. Levels of MR-proADM were significantly higher in patients who required vasoactive drugs (p = 0.02) or presented renal dysfunction (p = 0.004).Conclusion: PCT appeared to be superior to MR-proADM in diagnosing sepsis. Determining MR-proADM plasma levels at the initial phase of sepsis could be a useful tool for sepsis stratification and morbidity prediction before organ failure occurs. The present results need to be assessed with larger sample size studies.What is Known:•CRP and PCT are already included in clinical practice to assess sepsis and estimate disease severity, although their sensitivity and specificity are lower than desired.•ADM is a protein that has immune and vascular modulation actions, and its blood levels are increased in adult and paediatric sepsis.•ADM is a promising tool for early diagnosis and prognostic assessment in adult sepsis.What is New:•PCT appeared to be superior to MR-proADM in diagnosing paediatric sepsis.•MR-proADM plasma levels could be a useful tool for paediatric sepsis stratification and morbidity prediction.

OBJECTIVE: In 2016, Catalonia experienced a pediatric brainstem encephalitis outbreak caused by enterovirus A71 (EV-A71). Conventional testing identified EV in the periphery but rarely in CSF. Metagenomic next-generation sequencing (mNGS) and CSF pan-viral serology (VirScan) were deployed to enhance viral detection and characterization. METHODS: RNA was extracted from the CSF (n = 20), plasma (n = 9), stool (n = 15), and nasopharyngeal samples (n = 16) from 10 children with brainstem encephalitis and 10 children with meningitis or encephalitis. Pathogens were identified using mNGS. Available CSF from cases (n = 12) and pediatric other neurologic disease controls (n = 54) were analyzed with VirScan with a subset (n = 9 and n = 50) validated by ELISA. RESULTS: mNGS detected EV in all samples positive by quantitative reverse transcription polymerase chain reaction (qRT-PCR) (n = 25). In qRT-PCR-negative samples (n = 35), mNGS found virus in 23% (n = 8, 3 CSF samples). Overall, mNGS enhanced EV detection from 42% (25/60) to 57% (33/60) (p-value = 0.013). VirScan and ELISA increased detection to 92% (11/12) compared with 46% (4/12) for CSF mNGS and qRT-PCR (p-value = 0.023). Phylogenetic analysis confirmed the EV-A71 strain clustered with a neurovirulent German EV-A71. A single amino acid substitution (S241P) in the EVA71 VP1 protein was exclusive to the CNS in one subject. CONCLUSION: mNGS with VirScan significantly increased the CNS detection of EVs relative to qRT-PCR, and the latter generated an antigenic profile of the acute EV-A71 immune response. Genomic analysis confirmed the close relation of the outbreak EV-A71 and neuroinvasive German EV-A71. A S241P substitution in VP1 was found exclusively in the CSF.

Background: Enterovirus-A71 causes outbreaks of brainstem encephalitis, ranging from self-limited disease to acute flaccid paralysis. The aim of this study was to assess the role of cerebrospinal fluid (CSF) neopterin as a biomarker of disease severity in children with enterovirus-related brainstem encephalitis. Methods: A descriptive, prospective cohort study was conducted from April 2016 to March 2017 in a tertiary hospital. Pediatric patients with a diagnosis of brainstem encephalitis with or without myelitis due to enterovirus infection were enrolled. The final study group comprised a convenience sample including all patients with sufficient CSF volume for neopterin determination. The major variables considered in estimating the severity were the diagnosis of encephalomyelitis, the presence of lesions and extensive lesions on brain and spinal magnetic resonance imaging (MRI), hospital stay length greater than seven days, and sequelae at day 30. Results: Of 60 patients, CSF neopterin could be measured in 36. Median age was 26 months (interquartile range: 19 to 32). Thirty-three were diagnosed with brainstem encephalitis and three with encephalomyelitis. Enterovirus-A71 was the only identified genotype (25 of 25). CSF neopterin levels were elevated (>61 nmol/L) in 33 of 36 (92%), with a median of 347 nmol/L (interquartile range: 204 to 525). CSF neopterin was useful to distinguish patients with lesions on MRI (area under the receiver operating characteristic curve = 0.76; P = 0.02) and extensive lesions (area under the receiver operating characteristic curve = 0.76; P = 0.04). Conclusions: This study suggests an association between CSF neopterin levels and the presence of inflammatory lesions on MRI. (C) 2019 Elsevier Inc. All rights reserved.

Influenza is a generally a benign disease, but occasionally it can cause serious complications. There is controversy about the benefits of antiviral treatment.

INTRODUCTION AND OBJECTIVE: Children admitted to the pediatric intensive care unit after cardiovascular surgery usually require treatment with antibiotics due to suspicion of infection. The aim of this study was to assess the effectiveness of procalcitonin in decreasing the duration of antibiotic treatment in children after cardiovascular surgery. METHODS: Prospective, interventional study carried out in a pediatric intensive care unit. Included patients under 18 years old admitted after cardiopulmonary bypass. Two groups were compared, depending on the implementation of the PCT-guided protocol to stop or de-escalate the antibiotic treatment (Group 1, 2011-2013 and group 2, 2014-2018). This new protocol was based on the decrease of the PCT value by 20% or 50% with respect to the maximum value of PCT. Primary endpoints were mortality, stewardship indication, duration of antibiotic treatment, and antibiotic-free days. RESULTS: 886 patients were recruited. There were 226 suspicions of infection (25.5%), and they were confirmed in 38 cases (16.8%). The global rate of infections was 4.3%. 102 patients received broad-spectrum antibiotic (4.7±1.7 days in group 1, 3.9±1 days in group 2 with p = 0.160). The rate of de-escalation was higher in group 2 (30/62, 48.4%) than in group 1 (24/92, 26.1%) with p = 0.004. A reduction of 1.1 days of antibiotic treatment (group 1, 7.7±2.2 and group 2, 6.7±2.2, with p = 0.005) and 2 more antibiotic free-days free in PICU in group 2 were observed (p = 0.001), without adverse outcomes. CONCLUSIONS: Procalcitonin-guided protocol for stewardship after cardiac surgery seems to be safe and useful to decrease the antibiotic exposure. This protocol could help to reduce the duration of broad-spectrum antibiotics and the duration of antibiotics in total, without developing complications or adverse effects.

BACKGROUND: Seasonal influenza imposes a considerable burden worldwide. We aimed to evaluate impact of rapid pediatric seasonal influenza diagnosis on laboratory workflow and cost using a rapid antigen detection-based test combined with either a reverse transcriptase polymerase chain reaction (RT-PCR) or the Alere i Influenza A and B (Alere i) assay for confirmation of negative results as well as single Alere i testing on nasopharyngeal aspirates. A secondary objective was assessing performance of Alere i against RT-PCR. METHODS: Effects of implementing the 3 diagnostic algorithms were assessed in the Emergency Department of Hospital Sant Joan de Déu (Barcelona, Spain) across the 2014-2015, 2015-2016 and 2016-2017 influenza seasons. Alere i performance against RT-PCR was determined during the 2015-2016 epidemic period. RESULTS: Median time to result decreased when using Alere i as a confirmatory test of previous antigen detection and RT-PCR results or alone (9.7vs. 3.5/2.0 and 0.7 hours, P < 0.001) along with mean testing costs (&OV0556;87.3 vs. &OV0556;38.2 and &OV0556;25.0, P < 0.001). Results available before patient discharge from the emergency department increased from 42.7% for sequential testing by antigen detection and RT-PCR to 80.0% when Alere i was utilized as a stand-alone test. Alere i sensitivity and specificity values were 96.6% (95% confidence interval: 82.8%-99.4%) and 94.4% (95% confidence interval: 86.6%-97.8%), respectively. CONCLUSIONS: Rapid Alere i testing facilitated efficient laboratory workflow near the patient during influenza epidemics while contributing cost savings when compared with serial testing by antigen and RT-PCR assays.

Influenza is a generally a benign disease, but occasionally it can cause serious complications. There is controversy about the benefits of antiviral treatment.

OBJECTIVES: The objective of this study was to evaluate to evaluate the role of mannose-binding-lectin deficient genotypes in pneumococcal meningitis (PM) in children. METHODS: We performed a 16-year retrospective study (January 2001 to March 2016) including patients = 18 years with PM. Variables including attack rate of pneumococcal serotype (high or low invasive capacity) and MBL2 genotypes associated with low serum MBL levels were recorded. RESULTS: Forty-eight patients were included in the study. Median age was 18.5 months and 17/48 episodes (35.4%) occurred in children = 12 months old. Serotypes with high-invasive disease potential were identified in 15/48 episodes (31.2%). MBL2 deficient genotypes accounted for 18.8% (9/48). Children = 12 months old had a 7-fold risk (95% CI: 1.6-29.9; p < 0.01) of having a MBL2 deficient genotype in comparison to those > 12 months old. A sub-analysis of patients by age group revealed significant proportions of carriers of MBL2 deficient genotypes among those = 12 months old with PM caused by opportunistic serotypes (54.5%), admitted to the PICU (Pediatric Intensive Care Unit) (46.7%) and of White ethnicity (35.7%). These proportions were significantly higher than in older children (all p

Multiplex molecular techniques can detect a diversity of respiratory viruses and bacteria that cause childhood acute respiratory infection rapidly and conveniently. However, currently available techniques show high variation in performance. We sought to compare the diagnostic accuracy of the novel multiplex NxTAG respiratory pathogen panel (RPP) RUO test versus a routine multiplex Anyplex II RV16 assay in respiratory specimens collected from children

Human parechovirus-3 has been associated with severe clinical manifestations in infants, such as sepsis-like illness and meningoencephalitis. Nevertheless, the vast majority of patients have a favorable outcome. We report the occurrence of this infection in dizygotic infants with extreme hyperferritinemia and a transient impairment of natural killer cell cytotoxicity.