Tract Infections In Young Children Research Articles

Viral respiratory tract infections in young children with cystic fibrosis: a prospective full-year seasonal study

BackgroundViral respiratory tract infections are common during early childhood. How they impact cystic fibrosis lung disease history in young children is poorly known. The principal aim of our study was to determinate respiratory tract infections frequency in this cystic fibrosis young population. Secondary outcomes were nature of viral agents recovered and impact of such infections.MethodsWe conducted a prospective cohort study of 25 children affected by cystic fibrosis and aged less than 2 years. Nasal samplings were taken systematically monthly or bimonthly with additional samples taken during respiratory tract infections episodes. Ten pathogens were tested by a combination of five duplex RT-PCRs or PCRs: influenza A and B, respiratory syncytial virus (RSV), metapneumovirus (MPV), rhinovirus/enterovirus(RV/EV)), coronavirus (HKU1, NL63, 229E and OC43), parainfluenza virus (1–4), adenovirus and bocavirus (Respiratory Multi-Well System MWS r-gene®, BioMérieux, Marcy l’Étoile, France). Cycle thresholds (CTs) were reported for all positive samples and considered positive for values below 40. Quantitative variables were compared using a nonparametric statistical test (Wilcoxon signed rank for paired comparisons). Pearson’s correlation coefficient (r) was used to assess relationships between two variables. Statistical analyses were performed using SAS v9.4 (SAS Institute, Cary, NC, USA) or GraphPad Prism V6.00 (GraphPad Software, La Jolla, CA, USA). The significance level was set at 0.05.ResultsThe mean age at inclusion was 9.6 ± 6.7 months. The patients had 3.4 ± 1.7 respiratory tract infections episodes per child per year. Forty-four respiratory tract infections (69%) were associated with virus: rhinovirus and enterovirus (RV/EV) were implied in 61% of them and respiratory syncytial virus (RSV) in 14%. Only one patient required hospitalization for lower respiratory tract infections. 86% of the patients were treated by antibiotics for a mean of 13.8 ± 6.2 days. RSV infections (n = 6) were usually of mild severity.ConclusionsRespiratory tract infections in young children with cystic fibrosis were of mild severity, rarely requiring hospitalization. Unsurprisingly, RV/EV were the most frequent agents. RSV-related morbidity seems low in this population. This raises the question of the usefulness of RSV preventive medication in this young population.

Use of Chest Radiography Examination as a Probe for Pneumococcal Conjugate Vaccine Impact on Lower Respiratory Tract Infections in Young Children.

Community-acquired alveolar pneumonia (CAAP) is considered a bacterial disease, mainly pneumococcal. CAAP rates markedly declined following 7- and 13-valent pneumococcal conjugate vaccine (PCV) introductions worldwide. In contrast, non-CAAP lower respiratory tract infections (NA-LRIs) are generally not considered pneumococcal diseases. We assessed CAAP, NA-LRIs, and overall visits with chest radiograph (CXR) examination rates in the pediatric emergency room in southern Israel before and after PCV implementation. This was an ongoing, prospective observational study. Our hospital serves a captive population of approximately 75 000 children aged <5 years, enabling incidence calculation. PCV7 and PCV13 were implemented in Israel in July 2009 and November 2010, respectively. All CXRs were analyzed according to the World Health Organization Standardization of Interpretation. We calculated CAAP, NA-LRI, and CXR examinations annual incidences from 2004 to 2017 and incidence rate ratios comparing the PCV13 (2014-2017) with the pre-PCV (2004-2008) periods. Overall, 72 746 CXR examinations were recorded: 14% CAAP and 86% NA-LRI. CAAP, NA-LRI, and CXR examination visit rates declined by 49%, 34%, and 37%, respectively. This pattern was seen in Jewish and Bedouin children (the 2 ethnically distinct populations), with steeper declines observed among Jewish children and children aged >12 months. PCV7/PCV13 implementation resulted in a marked decline in CAAP and overall visits with CXR examination rates in young children. Overall, approximately 14 750 hospital visits with CXR were prevented annually per 100 000 population aged <5 years. These findings suggest that although NA-LRIs are usually not considered pneumococcal, many can be prevented by PCVs.Pneumococcal conjugate vaccine (PCV7/PCV13) implementation resulted in significant declines in community-acquired alveolar pneumonia (CAAP) and overall chest radiography examination rates in young children. Although non-CAAP lower respiratory tract infections are usually not considered pneumococcal, many can be prevented by PCVs.

Sequencing and analysis of globally obtained human parainfluenza viruses 1 and 3 genomes.

Human Parainfluenza viruses (HPIV) type 1 and 3 are important causes of respiratory tract infections in young children globally. HPIV infections do not confer complete protective immunity so reinfections occur throughout life. Since no effective vaccine is available for the two virus subtypes, comprehensive understanding of HPIV-1 and HPIV-3 genetic and epidemic features is important for diagnosis, prevention, and treatment of HPIV-1 and HPIV-3 infections. Relatively few whole genome sequences are available for both HPIV-1 and HPIV-3 viruses, so our study sought to provide whole genome sequences from multiple countries to further the understanding of the global diversity of HPIV at a whole-genome level. We collected HPIV-1 and HPIV-3 samples and isolates from Argentina, Australia, France, Mexico, South Africa, Switzerland, and USA from the years 2003–2011 and sequenced the genomes of 40 HPIV-1 and 75 HPIV-3 viruses with Sanger and next-generation sequencing with the Ion Torrent, Illumina, and 454 platforms. Phylogenetic analysis showed that the HPIV-1 genome is evolving at an estimated rate of 4.97 × 10−4 mutations/site/year (95% highest posterior density 4.55 × 10−4 to 5.38 × 10−4) and the HPIV-3 genome is evolving at a similar rate (3.59 × 10−4 mutations/site/year, 95% highest posterior density 3.26 × 10−4 to 3.94 × 10−4). There were multiple genetically distinct lineages of both HPIV-1 and 3 circulating on a global scale. Further surveillance and whole-genome sequencing are greatly needed to better understand the spatial dynamics of these important respiratory viruses in humans.

RSVpredict: An Online Tool to Calculate the Likelihood of Respiratory Syncytial Virus Infection in Children Hospitalized With Acute Respiratory Disease.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infection in young children. Early detection of RSV infection can avoid unnecessary diagnostic and therapeutic intervention and is required to prevent the nosocomial spread of RSV infection in pediatric hospitals. We developed a web tool to calculate the probability of RSV infection in children hospitalized with acute respiratory tract infection (ARTI) (RSVpredict). During winter seasons 2014/2015 to 2017/2018, 1545 children hospitalized with clinical symptoms of ARTI at the University Hospital Heidelberg/Germany were prospectively included. Medical information was reported on a standardized data sheet, and nasopharyngeal swabs were obtained for multiplex real-time polymerase chain reaction analyses. We applied logistic regression to develop a prediction model and developed a web-based application to predict the individual probability of RSV infection. Duration of clinical symptoms ≥2 days on admission, calendar month of admission, admission for lower respiratory tract infection, the presence of cough and rale and younger age were associated with RSV infection (P < 0.05). Those data were included in the prediction model (RSVpredict, https://web.imbi.uni-heidelberg.de/rsv/). RSVpredict is a web-based application to calculate the risk of RSV infection in children hospitalized with ARTI. The prediction model is based on easily accessible clinical symptoms and predicts the individual probability of RSV infection risk immediately. Pediatricians might use the RSVpredict to take informed decisions on further diagnostic and therapeutic intervention, including targeted RSV testing in children with relevant RSV infection risk.

Release of transglutaminase 2 from respiratory syncytial virus-infected airway epithelial cells and its role in disease pathogenesis

Abstract Respiratory syncytial virus (RSV) is the common cause of severe lower respiratory tract infections in young children, the elderly and the immunocompromised, for which no effective treatment or vaccine is currently available. RSV infections have also been linked to both the development and severity of asthma. Oxidative stress plays a major role in the pathogenesis of many lung inflammatory diseases. Our studies have shown that oxidative stress responses in the airways play a major role in the pathogenesis of RSV. Oxidative stress has been shown to elevate cytosolic calcium levels, which in turn activate calcium dependent enzymes, including transglutaminase 2 (TG2). TG2 is a transamidating acyltransferase that catalyzes Ca2+-dependent protein modifications and has been implicated in the pathogenesis of many diseases. This study’s objective was to investigate the release of TG2 in airway epithelial cells in response to RSV infection and its potential mechanism. Studies were conducted in airway epithelial cells, a human lung carcinoma cell line and normal small alveolar epithelial cells. The changes in the TG2 levels were measured by Western blot and RT-PCR after cells were pretreated with antioxidants and infected with RSV. TG2 levels were significantly increased in the secretome with a concomitant decrease in the cell lysates, cytoplasmic and nuclear extracts in response to RSV infection. Antioxidants treatment significantly inhibited RSV-induced TG2 release. TG2 release was induced only by RSV but not RSV-induced cytokines or chemokines. These results suggest that modulation of oxidative stress represents a potential novel pharmacological approach to ameliorate virus-induced acute airway disease through TG2 release blockade.

Comparative evaluation of nebulised 3% saline versus nebulised 0.9% saline in the treatment of acute bronchiolitis

Background: Acute bronchiolitis is the most common respiratory tract infection in young children. Despite the high prevalence of acute bronchiolitis, no consensus exists on the management. Studies have shown that except oxygen therapy, no other treatment found to be effective. Hence, the present study was conducted to find out the efficacy of nebulised 3% saline versus is 0.9% saline for the treatment of acute bronchiolitis.Methods: A prospective randomized controlled study of 150 children between the age group of 2 months to 24 months with signs and symptoms of Acute Bronchiolitis admitted to Indira Gandhi Institute of Child Health, Bangalore from January 2016 to December 2016 formed the study group, they were randomized into 2 groups, one received 3% saline nebulization and the other received 0.9% saline.Results: A total of 150 children were enrolled in the study, 75 children (group A) received 0.9% saline and 75 children (group B) received 3% saline. At 24 hours, the mean clinical severity score for group A was 2.49±1.03 and group B was 2.16±0.49 (P=0.013). The duration of hospital stay was shorter (1-3 days) in 3% saline with a mean of 2.35 days and was longer (3-5 days) in 0.9% saline with mean value of 4.04 days which was statistically significant (p &lt;0.001).Conclusions: 3% saline nebulization can be used as an effective treatment for acute bronchiolitis. It significantly reduced the clinical severity score and length of hospital stay compared to 0.9% normal saline.

Author Reply

We appreciate the thoughtful response to our study findings and agree that the medical community should re-evaluate the American Academy of Pediatrics guidelines for febrile urinary tract infections. While the guidelines rely on the use of renal and bladder ultrasound findings to determine the need for VCUGs, several previous investigations have shown that ultrasound findings are a poorly predictive of VCUG abnormalities. Hoberman et al determined that identification of urinary tract dilation on renal ultrasound following the first febrile urinary tract infection had only a 10% sensitivity and 40% positive predictive value for detection of vesicoureteral reflux on VCUG among 302 children. 1 Hoberman A Charron M Hickey RW Baskin M Kearney DH Wald ER Imaging studies after a first febrile urinary tract infection in young children. N. Engl. J. Med. 2003; 348: 195-202 Crossref PubMed Scopus (562) Google Scholar These results were corroborated by Juliano et al, who reported evidence of dilating vesicoureteral reflux among 23/84 children with a normal renal ultrasound. 2 Juliano TM Stephany HA Clayton DB et al. Incidence of abnormal imaging and recurrent pyelonephritis after first febrile urinary tract infection in children 2 to 24 months old. J. Urol. 2013; 190: 1505-1510 Crossref PubMed Scopus (40) Google Scholar A larger study by Logvinenko et al revealed that renal ultrasound had a sensitivity of only 32% for detecting grade 3-5 vesicoureteral reflux among nearly 4000 patients. The group concluded that ultrasound was a poor screening tool for diagnosis of high-grade vesicoureteral reflux. 3 Logvinenko T Chow JS Nelson CP Predictive value of specific ultrasound findings when used as a screening test for abnormalities on VCUG. J Pediatr Urol. 2015; 11 (e171-177): 176 Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar The use of renal ultrasound findings to guide VCUG administration, therefore, should be called into question. It is perhaps for this reason that guideline adherence did not improve vesicoureteral reflux detection among children aged 2-24 months in our patient cohort.

Nebulised hypertonic saline in children with bronchiolitis admitted to the paediatric intensive care unit: A retrospective study

Bronchiolitis is one of the most common lower respiratory tract infections in young children, associated with significant morbidity, but limited therapeutic options. Nebulised hypertonic saline (HS) has been a supportive treatment until current guidelines advised against its routine use. Accordingly, the University Hospital of Antwerp recently changed their policies to stop using it, allowing us to evaluate retrospectively if HS influences the duration of respiratory support. Because, to our knowledge, the effect of HS on children with severe bronchiolitis admitted to a paediatric intensive care unit (PICU) has not been studied yet, we aimed to investigate the effect in this specific patient group. Retrospective study including children up to the age of 2, admitted to the PICU with bronchiolitis from October 2013 until March 2016. The primary end point is the duration of respiratory support, including high flow nasal cannula, continuous positive airway pressure and invasive ventilation. A total of 104 children admitted to the PICU with bronchiolitis were included, with an average age of 3.4 months. In respiratory syncytial virus (RSV) positive patients, the use of nebulised HS was correlated with a decrease in the duration of respiratory support and the length of stay by factors 0.72 (P = 0.01) and 0.81 (P = 0.04), respectively. A significant correlation was found between the use of HS and a decreased duration of respiratory support and admission in the PICU in patients with RSV bronchiolitis. This finding may warrant new prospective studies investigating HS specifically in children with severe bronchiolitis.

Obesity and risk of urinary tract infection in young children presenting with fever.

Obesity may increase the risk of infection, but the association between obesity and febrile urinary tract infection (fUTI) is controversial. Although the prevalence of infant and childhood obesity has been increasing worldwide, the results of previous investigations on the association with urinary tract infection (UTI) are conflicting. The purpose of this study was to evaluate the relationship between overweight and obesity and UTI in febrile children.The study reviewed medical records of a consecutive series of 472 children <2 years of age presenting with fever ≥ 38°C were retrospectively evaluated and stratified by the presence or absence of a UTI. The proportions of underweight, healthy weight, overweight, and obese children in the 2 groups were compared following calculation of individual weight-for-length percentiles. The effect of obesity on UTI risk was evaluated, and odds ratios (ORs) were calculated.A total of 212 patients with and 260 controls without UTI were included. There were more overweight and obese children with (71/212, 33.5%) than without UTIs (45/260, 17.3%; P < .001). The OR of UTI in overweight relative to healthy-weight children was 1.92 [95% confidence interval (95% CI):1.15–3.21]. The OR of UTI in obese relative to healthy weight children was 2.46 (95% CI: 1.54–3.93).Compared with previous studies that made comparison between UTI and healthy children, this is the first study to demonstrate an association of obesity and fUTI in febrile children <2 years of age. In this series of pediatric patients, obesity was strongly associated with the presence of fUTI and obese children had a higher risk of developing an UTI than nonobese children.The incidence of UTI was higher in young, overweight, and obese children presenting with fever than in normal-weight, febrile children. Control of excess body weight should be considered as early as possible. Urinalysis should be considered for obese children <2 years of age who present with fever, especially those with mild respiratory or gastrointestinal symptoms.

Management of Urinary Tract Infections in Young Children: Balancing Admission With the Risk of Emergency Department Revisits

ObjectiveOral antibiotics effectively treat most pediatric urinary tract infections (UTIs); however, children with UTIs are frequently admitted. We examined variation and trends in admission for children with UTIs plus investigated the relationship between admission and emergency department (ED) revisits for those initially managed on an outpatient basis. We hypothesized that hospitals would have similar 3-day revisit rates regardless of the admission rate at the index visit. MethodsThis was a retrospective analysis of 36 hospitals in the Pediatric Health Information System. ED visits for children aged <2 years presenting with UTI between 2010 and 2016 were studied. Main outcomes were age-stratified and included admission and 3-day ED revisit rates. Regression analyses were used to test hospital-level associations between outcomes and linear temporal trends. ResultsA total of 41,792 visits were studied. The overall admission rate was 27%. The admission rate was 89% for children aged <2 months and 15% for those aged 2 to 24 months. Interhospital admission rates varied from 6% to 64%. Admission and revisit rates were inversely related (mean change, –0.07; 95% confidence interval [CI], –0.13 to –0.02 per 1% increase in admission rate); however, lower admission rates were not associated with increased revisits leading to admission (mean change, –0.02; 95% CI, –0.07 to 0.03). Over the study period, admission rates were stable (test for linear trend: adjusted odds ratio [aOR], 0.99; 95% CI, 0.95–1.02); however, among infants aged <2 months, admissions decreased (aOR, 0.92; 95% CI, 0.88–0.97). ConclusionsA substantial variation in admission rates exists for children with UTI. Although hospitals with lower admission rates had higher revisit rates, those hospitals did not have an increase in revisits with subsequent admission, supporting the goal of outpatient management.

P165 Hyperglycemia may predispose to lower respiratory tract infection in young children with cystic fibrosis

P165 Hyperglycemia may predispose to lower respiratory tract infection in young children with cystic fibrosis

Human Metapneumovirus Infection Inhibits Cathelicidin Antimicrobial Peptide Expression in Human Macrophages.

Human cathelicidin antimicriobial peptide (CAMP) is a critical component of host innate immunity with both antimicrobial and immunomodulatory functions. Several pathogens have been shown to downregulate CAMP expression, yet it is unclear if such modulation occurs during a viral infection. In this study, we showed that infection with human metapneumovirus (hMPV), one of the leading causes of respiratory tract infections in young children, strongly suppressed basal and vitamin-D induced CAMP expression in human macrophages. hMPV-mediated suppression of CAMP did not correlate with reduced transcriptional expression of key vitamin D signaling components, such as CYP27B1 or vitamin D receptor, suggesting a vitamin D-independent mechanism. Blocking interferon-signaling pathways did not reverse hMVP-mediated suppression of CAMP, indicating that the suppressive effect is largely interferon-independent. Instead, we identified C/EBPα as the key modulator of hMPV-mediated suppression of CAMP. hMPV infection strongly repressed the expression of C/EBPα, and a knockdown study confirmed that C/EBPα is critical for CAMP expression in human macrophages. Such modulation of CAMP (and C/EBPα) could be reproduced by TLR1/2 ligand treatment in human macrophages, suggesting a common mechanism underlying pathogen-mediated downregulation of CAMP through C/EBPα. This study opens up a new understanding of altered human antimicrobial responses following infections.

Detrimental role of type I interferon signaling in respiratory syncytial virus infection

Abstract Respiratory Syncytial Virus (RSV), the primary cause of lower respiratory tract infections in young children, is a poor inducer of type I interferons (IFN) and is resistant to its canonical antiviral activity. Paradoxically, increased type I IFN has been observed in some studies to correlate with more severe disease in RSV-infected children. Previously, we have shown that a pathogenic reactive oxygen species (ROS) production in the course of RSV infection is caused by a progressive reduction in nuclear and cellular levels of the transcription factor NF-E2-related factor 2 (NRF2), the primary regulator of antioxidant enzyme (AOE) gene expression. Thus, the goal of this study was to determine the contribution of type I IFN to lung innate/inflammatory responses, modulation of AOE expression, and airway disease in experimental RSV infection. Using either IFN alpha/beta receptor knockout mice or IFNAR neutralizing antibody, we found that IFN signaling blockade attenuated RSV-mediated NRF2 degradation and rescued AOE levels (i.e. SOD 1 and Catalase) in the lung, resulting in improved airway function and clinical disease. We also showed that NRF2/AOE rescue in mice lacking IFN signaling is due to the reduced expression of the promyelocytic leukemia protein (PML), a key component of PML nuclear bodies. In addition, levels of RSV-induced pro-inflammatory cytokines including IL-1α/β, IL-6, IL-12(p40), TNF-α, and the chemokines CXCL1, CCL2, 3, 4, and 5 were also reduced in IFN deficient mice. In conclusion, this data shows for the first time that IFN type I signaling plays a critical role in enhancing RSV-mediated airway disease through an innate immune pathways that involve the PML-NRF2-AOE axis.

Comparison of risk factors for, and prevalence of, antibiotic resistance in contaminating and pathogenic urinary Escherichia coli in children in primary care: prospective cohort study

BackgroundAll-cause antibiotic prescribing affects bowel flora antimicrobial susceptibility, and may increase risk of urinary autoinoculation with antibiotic-resistant microbes. However, little is known about relative prevalence of, or risk factors for, antimicrobial resistance among potentially pathogenic microbes thought to be contaminating and infecting urine.MethodsSecondary analysis of 824 children under 5 years of age consulting in primary care for an acute illness and their Escherichia coli isolates cultured at ≥103 cfu/mL from the Diagnosis of Urinary Tract infection in Young children (DUTY) study. Multivariable logistic regression investigating risk factors for resistance to amoxicillin, co-amoxiclav, cefalexin, ciprofloxacin, trimethoprim, nitrofurantoin and cefpodoxime in microbes meeting the laboratory criteria for urinary tract infection: ‘pathogens’ (>105 cfu/mL, n = 79) and ‘contaminants’ (103 to 105 cfu/mL, n = 745).ResultsForty-three percent of E. coli were resistant to at least one tested antibiotic, with resistance highest to amoxicillin (49.37% pathogenic versus 37.32% contaminant, P = 0.04), trimethoprim (27.85% versus 16.52%, P = 0.01) and co-amoxiclav (16.46% versus 21.48%, P = 0.30). Multidrug resistance (to ≥3 antibiotic groups) was present in 17.07% of pathogens and 30.13% of contaminants (P = 0.04). No isolates were resistant to nitrofurantoin. Recent (0–3 months) exposure to antibiotics was associated with resistance in both pathogens (aOR: 1.10, 95% CI: 1.01–4.39) and contaminants (1.69, 1.09–2.67).ConclusionsPrevalence of resistance (including multidrug) was high, but there was no consistent relationship between isolate pathogen/contamination status and resistance. Recent all-cause antibiotic prescribing increased the probability of antimicrobial resistance in both pathogenic and contaminating urinary E. coli in children in primary care.

Molecular epidemiology of respiratory syncytial virus.

Respiratory syncytial virus (RSV) is a major cause of viral acute respiratory tract infections in young children. The virus is characterised by distinct seasonality that is dependent upon the latitude and its ability to cause reinfection. Respiratory syncytial virus demonstrates a complex molecular epidemiology pattern as multiple strains and/or genotypes cocirculate during a single epidemic. Previous studies have investigated the relationship between RSV genetic diversity, reinfection, and clinical features. Here, we review the evidence behind this relationship together with the impact that the advancement of whole genome sequencing will have upon our understanding and the need for reconsidering the classification of RSV genotypes.

Respiratory syncytial virus infection in children less than five years of age presenting as severe community-acquired pneumonia

Background: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in young children in both the community and hospital setting. Ongoing surveillance of the clinical and molecular epidemiology of RSV genotypes is important to characterize prevalent and emerging genotypes that may have impact on vaccine development. Objective: To assess the epidemiology of RSV infection in children &lt;5 years of age in a tertiary care hospital. Materials and Methods: Children &lt;5 years of age hospitalized with severe community-acquired pneumonia (CAP) were included in the study. Nasopharyngeal aspirate was taken for RSV reverse-transcriptase polymerase chain reaction. Results: A total of 100 children were recruited in the study. clinicoepidemiological epidemiological and radiological features were analyzed. The prevalence of RSV infection in children &lt;60 months of age admitted with the features of severe pneumonia in our study was 30% with almost equal proportion of RSV A and B groups. Underlying congenital heart disease and family history of asthma were identified as significant risk factors. There were no significant clinical and radiological features to distinguish RSV from non-RSV disease. Conclusions: This study highlights the relevance of RSV infection in hospitalized cases of CAP in our region. Our findings warrant the conduct of further investigations which can help design strategies for controlling the disease. If RT-PCR could be used in children with severe pneumonia who are hospitalized, an accurate diagnosis of RSV bronchiolitis can be made in high percentage of children.

Antibiotic prescribing quality for children in primary care: an observational study.

Overuse and inappropriate prescribing of antibiotics is driving antibiotic resistance. GPs often prescribe antibiotics for upper respiratory tract infections (URTIs) in young children despite their marginal beneficial effects. To assess the quality of antibiotic prescribing for common infections in young children attending primary care and to investigate influencing factors. An observational, descriptive analysis, including children attending primary care sites in England and Wales. The Diagnosis of Urinary Tract infection in Young children study collected data on 7163 children aged <5 years, presenting to UK primary care with an acute illness (<28 days). Data were compared with the European Surveillance of Antimicrobial Consumption Network (ESAC-Net) disease-specific quality indicators to assess prescribing for URTIs, tonsillitis, and otitis media, against ESAC-Net proposed standards. Non-parametric trend tests and χ2 tests assessed trends and differences in prescribing by level of deprivation, site type, and demographics. Prescribing rates fell within the recommendations for URTIs but exceeded the recommended limits for tonsillitis and otitis media. The proportion of children receiving the recommended antibiotic was below standards for URTIs and tonsillitis, but within the recommended limits for otitis media. Prescribing rates increased as the level of deprivation decreased for all infections (P<0.05), and increased as the age of the child increased for URTIs and tonsillitis (P<0.05). There were no other significant trends or differences. The quality of antibiotic prescribing in this study was mixed and highlights the scope for future improvements. There is a need to assess further the quality of disease-specific antibiotic prescribing in UK primary care settings using data representative of routine clinical practice.

Performance of the Alere i RSV assay for point-of-care detection of respiratory syncytial virus in children

BackgroundRespiratory syncytial virus (RSV) is the most important cause of severe acute respiratory tract infection in young children. Alere i RSV is a novel molecular rapid test which identifies respiratory syncytial virus in less than 13 min.MethodsWe evaluated the clinical performance of the Alere i RSV assay in a pediatric point-of-care setting during winter season 2016 / 2017. Test results from 518 nasopharyngeal swab samples were compared to a real-time reverse transcription PCR reference standard.ResultsThe overall sensitivity and specificity of the Alere i RSV test assay was 93% (CI95 89% – 96%) and 96% (CI95 93% – 98%), respectively. Alere i RSV performed well in children of all age groups. An optimal sensitivity of 98% (CI95 94% - 100%) and specificity of 96% (CI95 90% - 99%) was obtained in children < 6 months. In children ≥ 2 years, sensitivity and specificity remained at 87% (CI95 73% – 96%) and 98% (CI95 92% – 100%), respectively. False negative Alere i RSV test results mostly occurred in samples with low viral load (mean CT value 31.1; CI95 29.6 – 32.6). The Alere i RSV assay is easy to use and can be operated after minimal initial training. Test results are available within 13 min, with most RSV positive samples being identified after approximately 5 min.ConclusionThe Alere i RSV assay has the potential to facilitate the detection of RSV in pediatric point-of-care settings.

Human Parvovirus Infection of Human Airway Epithelia Induces Pyroptotic Cell Death by Inhibiting Apoptosis.

Human bocavirus 1 (HBoV1) is a human parvovirus that causes acute respiratory tract infections in young children. In this study, we confirmed that, when polarized/well-differentiated human airway epithelia are infected with HBoV1 in vitro, they develop damage characterized by barrier function disruption and cell hypotrophy. Cell death mechanism analyses indicated that the infection induced pyroptotic cell death characterized by caspase-1 activation. Unlike infections with other parvoviruses, HBoV1 infection did not activate the apoptotic or necroptotic cell death pathway. When the NLRP3-ASC-caspase-1 inflammasome-induced pathway was inhibited by short hairpin RNA (shRNA), HBoV1-induced cell death dropped significantly; thus, NLRP3 mediated by ASC appears to be the pattern recognition receptor driving HBoV1 infection-induced pyroptosis. HBoV1 infection induced steady increases in the expression of interleukin 1α (IL-1α) and IL-18. HBoV1 infection was also associated with the marked expression of the antiapoptotic genes BIRC5 and IFI6 When the expression of BIRC5 and/or IFI6 was inhibited by shRNA, the infected cells underwent apoptosis rather than pyroptosis, as indicated by increased cleaved caspase-3 levels and the absence of caspase-1. BIRC5 and/or IFI6 gene inhibition also significantly reduced HBoV1 replication. Thus, HBoV1 infection of human airway epithelial cells activates antiapoptotic proteins that suppress apoptosis and promote pyroptosis. This response may have evolved to confer a replicative advantage, thus allowing HBoV1 to establish a persistent airway epithelial infection. This is the first report of pyroptosis in airway epithelia infected by a respiratory virus.IMPORTANCE Microbial infection of immune cells often induces pyroptosis, which is mediated by a cytosolic protein complex called the inflammasome that senses microbial pathogens and then activates the proinflammatory cytokines IL-1 and IL-18. While virus-infected airway epithelia often activate NLRP3 inflammasomes, studies to date suggest that these viruses kill the airway epithelial cells via the apoptotic or necrotic pathway; involvement of the pyroptosis pathway has not been reported previously. Here, we show for the first time that virus infection of human airway epithelia can also induce pyroptosis. Human bocavirus 1 (HBoV1), a human parvovirus, causes lower respiratory tract infections in young children. This study indicates that HBoV1 kills airway epithelial cells by activating genes that suppress apoptosis and thereby promote pyroptosis. This strategy appears to promote HBoV1 replication and may have evolved to allow HBoV1 to establish persistent infection of human airway epithelia.

Should the Absence of Urinary Nitrite Influence Empiric Antibiotics for Urinary Tract Infection in Young Children?

Screening for urinary tract infection (UTI) includes urinary nitrite testing by dipstick urinalysis. Gram-negative enteric organisms produce urinary nitrite and represent the most common uropathogens. Enterococcus, a less common uropathogen, does not produce nitrite and has a unique antibiotic resistance pattern. Whether to adjust empiric antibiotics in the absence of urinary nitrite has not been established. Our primary objective was to determine prevalence of enterococcal UTI among young children with a nitrite negative urinalysis. A retrospective study of children aged less than 2 years evaluated in the emergency department for possible UTI and had a paired urinalysis and urine culture was performed. Urinary tract infection was defined by catheterized culture yielding greater than or equal to 50,000 colony-forming units per milliliter of a single uropathogen. Prevalence of uropathogens among nitrite negative samples was studied. A total of 7599 children were studied. Median (interquartile range) age was 5.6 (2.3-11.2) months, and 57% were female. Prevalence of UTI was 8.1%. Enterococcus was the uropathogen in 2.1% of UTIs, and all cases had negative dipstick nitrite. Among nitrite negative UTIs, 95.6% of uropathogens were gram-negative and only 3.2% (confidence interval, 1.8%-5.3%) were enterococcus. None of the 200 UTIs with positive nitrite yielded enterococcus (upper confidence interval, 1.4%). Among children with positive leukocyte esterase and negative nitrite, only 0.7% of cases had enterococcal UTI. Only 3% of nitrite negative UTIs were caused by enterococcus. Given the low prevalence of enterococcal UTI, the absence of dipstick nitrite should not affect routine empiric antibiotic choice for presumptive UTI in young children.