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Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS) is a combined immunodeficiency caused by gain-of-function mutations in the C-X-C chemokine receptor type 4 (CXCR4) gene. We characterize a unique international cohort of 66 patients, including 57 (86%) cases previously unreported, with variable clinical phenotypes. Of 17 distinct CXCR4 genetic variants within our cohort, 11 were novel pathogenic variants affecting 15 individuals (23%). All variants affect the same CXCR4 region and impair CXCR4 internalization resulting in hyperactive signaling. The median age of diagnosis in our cohort (5.5 years) indicates WHIM syndrome can commonly present in childhood, although some patients are not diagnosed until adulthood. The prevalence and mean age of recognition and/or onset of clinical manifestations within our cohort were infections 88%/1.6 years, neutropenia 98%/3.8 years, lymphopenia 88%/5.0 years, and warts 40%/12.1 years. However, we report greater prevalence and variety of autoimmune complications of WHIM syndrome (21.2%) than reported previously. Patients with versus without family history of WHIM syndrome were diagnosed earlier (22%, average age 1.3 years versus 78%, average age 5 years, respectively). Patients with a family history of WHIM syndrome also received earlier treatment, experienced less hospitalization, and had less end-organ damage. This observation reinforces previous reports that early treatment for WHIM syndrome improves outcomes. Only one patient died; death was attributed to complications of hematopoietic stem cell transplantation. The variable expressivity of WHIM syndrome in pediatric patients delays their diagnosis and therapy. Early-onset bacterial infections with severe neutropenia and/or lymphopenia should prompt genetic testing for WHIM syndrome, even in the absence of warts.

BACKGROUNDRespiratory syncytial virus (RSV) is the leading cause of hospitalisation associated with acute respiratory infection in infants and young children, with substantial disease burden globally. The impact of additional respiratory pathogens on RSV disease severity is not completely understood.OBJECTIVESThe objective of this study was to explore the associations between RSV disease severity and the presence of other respiratory pathogens.METHODSNasopharyngeal swabs were prospectively collected from two infant cohorts: a prospective longitudinal birth cohort study and an infant cross-sectional study recruiting infants RESULTSRSV was detected in 433 infants. Nearly one in four of the infants (24%) harboured at least one additional non-RSV respiratory virus, with human rhinovirus being the most frequently detected (15% of the infants), followed by seasonal coronaviruses (4%). In this cohort, RSV-infected infants harbouring any other virus tended to be older (median age: 4.3 vs. 3.7 months) and were more likely to require intensive care and mechanical ventilation than those who did not.Moraxella, Streptococcus, andHaemophilusspecies were the most frequently identified target bacteria, together found in 392 (91%) of the 433 infants (S. pneumoniaein 51% of the infants andH. influenzaein 38%). The strongest contributors to severity of presentation were younger age and the co-detection ofHaemophilusspecies alongside RSV. Across all age groups in both cohorts, detection ofHaemophilusspecies was associated with higher overall severity, as captured by ReSVinet scores, and specifically with increased rates of hospitalisation and respiratory distress. In contrast, presence ofMoraxellaspecies was associated with lower ReSVinet scores and reduced need for intensive care and mechanical ventilation. Infants with and withoutStreptococcusspecies (orS. pneumoniaein particular) had similar clinical outcomes. No specific RSV strain was associated with co-detection of other pathogens.CONCLUSIONOur findings provide strong evidence for associations between RSV disease severity and the presence of additional respiratory viruses and bacteria. The associations, while not indicating causation, are of potential clinical relevance. Awareness of coexisting microorganisms could inform therapeutic and preventive measures to improve the management and outcome of RSV-infected infants.

OBJECTIVE: The need for pediatric antifungal stewardship programs has been driven by an increasing consumption of antifungals for prophylactic and empirical use. Drivers and rational of antifungal prescribing need to be identified to optimize prescription behaviors. METHODS: A prospective modified weekly Point Prevalence Survey capturing antifungal prescriptions for children (> 90 days to < 18 years of age) in 12 centers in England during 26 consecutive weeks was performed. Demographic, diagnostic and treatment information was collected for each patient. Data were entered into an online REDCap database. RESULTS: One thousand two hundred fifty-eight prescriptions were included for 656 pediatric patients, 44.9% were girls, with a median age of 6.4 years (interquartile range, 2.5-11.3). Most common underlying condition was malignancy (55.5%). Four hundred nineteen (63.9%) received antifungals for prophylaxis, and 237 (36.1%) for treatment. Among patients receiving antifungal prophylaxis, 40.2% did not belong to a high-risk group. In those receiving antifungal treatment, 45.9%, 29.4%, 5.1% and 19.6% had a diagnosis of suspected, possible, probable of proven invasive fungal disease (IFD), respectively. Proven IFD was diagnosed in 78 patients, 84.6% (n = 66) suffered from invasive candidiasis and 15.4% (n = 12) from an invasive mold infection. Liposomal amphotericin B was the most commonly prescribed antifungal for both prophylaxis (36.6%) and empiric and preemptive treatment (47.9%). Throughout the duration of the study, 72 (11.0%) patients received combination antifungal therapy. CONCLUSIONS: Antifungal use in pediatric patients is dominated by liposomal amphotericin B and often without evidence for the presence of IFD. A significant proportion of prophylactic and empiric antifungal use was seen in pediatric patients not at high risk for IFD.

Summary Objectives Bacterial infections are a major cause of UK paediatric hospitalisations, yet longitudinal data on causative organisms or antimicrobial resistance are scarce. This retrospective analysis describes trends in blood and cerebrospinal fluid (CSF) cultures and resistance patterns in children under three years old from a large UK centre. Methods All culture results, and resistance data for Gram-negative rods (GNR) in blood cultures, collected between January 2005 and December 2018 were extracted from Oxford University Hospitals NHS Foundation Trust microbiology database. Results Of 49,298 samples, 6.7% of blood and 3.1% of CSF cultures were positive for bacterial growth; 2.3% and 1.1%, respectively grew pathogens. Number of cultures taken increased over time; the proportion growing pathogens declined. Resistance of GNR to first-line antimicrobials was 9.3% to gentamicin (neonatal units), and 17.1% and 25.8% to ceftriaxone (paediatric ED and wards respectively). Resistance to any two of ceftriaxone, ciprofloxacin, gentamicin, or meropenem was ≤ 6% in both areas. Conclusions The proportion of positive cultures declined over time. Resistance of GNR to empirical antimicrobials were observed, but resistance to a second agent were lower. Our study informs clinician decisions on when, and to which antimicrobials, to escalate if a child is not improving on empirical therapy.

Congenital human cytomegalovirus (CMV) infection is the most common congenital infection, affecting around 1 in 200 infants in high-income settings. It can have life-long consequences for up to one in four children, including sensorineural hearing loss and neurodisability. Despite the frequency of congenital CMV and the severity for some children, it is a little-known condition by pregnant women, families and healthcare providers. Timely diagnosis of CMV infection in pregnancy is important to facilitate consideration of treatment with valaciclovir, which may reduce the risk of transmission to the fetus or reduce the severity of the outcomes for infected infants. Recognition of features of congenital CMV is important for neonatologists, paediatricians and audiologists to prompt testing for congenital CMV within the first 21 days of life. Early diagnosis gives the opportunity for valganciclovir treatment, where appropriate, to improve outcomes for affected infants. Further research is urgently needed to inform decisions about antenatal and neonatal screening, long-term outcomes for asymptomatic and symptomatic infants, predictors of these outcomes and optimal treatment for women and infants.

Introduction: Chronic infection with human T-cell lymphotropic virus type-1 (HTLV-1) may result in aggressive adult T-cell leukaemia/lymphoma (ATL) in 4-6% carriers. The majority of this risk arises in carriers infected during infancy, and so each infant has ∼25% lifetime risk. Other risk factors include a family history of ATL. Antenatal HTLV-1 screening is not undertaken in the UK. Methods: Here we describe four cases of ATL diagnosed during pregnancy and describe strategies to minimise HTLV-1 transmission to neonates. Results/conclusion: These cases highlight undiagnosed HTLV-1 in pregnancy which allows ongoing mother to child vertical transmission and risk of future ATL. We recommend the UK National Screening Committee incorporate HTLV-1 serology into antenatal screening.

We present a case of a 17-year-old boy with X-linked agammaglobulinemia who had mild disease when initially infected with SARS-CoV-2 but after recovering from acute infection developed fevers and a raised erythrocyte sedimentation rate that persisted for several weeks without any ongoing respiratory symptoms. Multiple nasopharyngeal swabs were found to be negative for SARS-CoV-2 during the febrile period, but typical changes of COVID-19 on high resolution CT chest scan led to the detection of SARS-CoV-2 on RT-PCR in a sample from a bronchoalveolar lavage. His fevers completely resolved after a 5-day course of remdesivir.

Human respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in young children globally, but little is known about within-host RSV diversity. Here, we characterised within-host RSV populations using deep-sequencing data from 319 nasopharyngeal swabs collected during 2017-2020. RSV-B had lower consensus diversity than RSV-A at the population level, while exhibiting greater within-host diversity. Two RSV-B consensus sequences had an amino acid alteration (K68N) in the fusion (F) protein, which has been associated with reduced susceptibility to nirsevimab (MEDI8897), a novel RSV monoclonal antibody under development. In addition, several minor variants were identified in the antigenic sites of the F protein, one of which may confer resistance to palivizumab, the only licensed RSV monoclonal antibody. The differences in within-host virus populations emphasise the importance of monitoring for vaccine efficacy and may help to explain the different prevalences of monoclonal antibody-escape mutants between the two subgroups.

We present a case of initial seronegative West Nile virus encephalitis in an immunocompromised child due to B-cell acute lymphoblastic leukemia. Although diagnostic guidelines for West Nile virus infection exist, we highlight that these may not be met in immunocompromised patients who may have a delayed immune response.

Respiratory syncytial virus (RSV) is responsible for a large burden of disease globally and can present as a variety of clinical syndromes in children of all ages. Bronchiolitis in infants under 1 year of age is the most common clinical presentation hospitalizing 24.2 per 1000 infants each year in the United Kingdom. RSV has been shown to account for 22% of all episodes of acute lower respiratory tract infection in children globally. RSV hospitalization, that is, RSV severe disease, has also been associated with subsequent chronic respiratory morbidity. Routine viral testing in all children is not currently recommended by the United Kingdom National Institute for Health and Care Excellence (NICE) or the American Academy of Pediatrics (AAP) guidance and management is largely supportive. There is some evidence for the use of ribavirin in severely immunocompromised children. Emphasis is placed on prevention of RSV infection through infection control measures both in hospital and in the community, and the use of the RSV-specific monoclonal antibody, palivizumab, for certain high-risk groups of infants. New RSV antivirals and vaccines are currently in development. Ongoing work is needed to improve the prevention of RSV infection, not only because of the acute morbidity and mortality, but also to reduce the associated chronic respiratory morbidity after severe infection.

Globally, respiratory syncytial virus (RSV) is a major cause of infant morbidity and mortality. Natural infection offers limited protection against reinfection. Passive immunization with RSV-specific antibody can protect infants against severe lower respiratory tract infection (LRTI). This suggests that vaccine-induced antibody could benefit infants and therefore supports maternal vaccination as a potential strategy for protecting young infants. The duration of such protection will dictate the need and timing for additional infant vaccines which are under development. For high-risk groups of passive immunization with monoclonal antibodies continues to be standard approach. With novel monoclonal antibodies that have a longer half-life and lower cost the strategy may be extended to healthy infants.

Background: Bacillus Calmette–Guérin (BCG) is a live-attenuated vaccine used world-wide for prevention of tuberculosis disease. In some immunocompromised hosts it has the potential to cause disease. As with other members of the M. tuberculosis complex it has the potential for acquiring drug resistance. Methods: We reviewed 10 years of paediatric clinical BCG strains referred to our clinical microbiology laboratory in Oxford where they underwent whole genome sequencing. We present a case series comparing clinical, pathogen genetic and pathogen phenotypic data, and consider the clinical implications. Results: We identified 15 BCG isolates from 8 children under 16 years old. Only one child had clinical disease with the other seven reported as local inoculation-site reactions. Case 1 suffered disseminated disease secondary to an undiagnosed IL-12/IFNγ receptor defect and the BCG isolates evolved two different rifampicin resistance mutations. Across all 15 isolates, phenotypic resistance to each first line drug was seen. Conclusions: BCG is a safe and effective vaccine in children. Most clinical specimens in our series were not related to disease. However, in the context of rare pathogen-specific immunocompromise, BCG can cause pathology and acquire drug resistance under selection from therapy.

Paediatric virology is a bold, new scientific field, where paediatrics focuses on the newly acquired knowledge from clinical virology, enriched with current advances in epidemiology, molecular medicine, evidence-based medicine, clinical governance, quality improvement, pharmacology and immunology. Although there are several methods with which to obtain training in paediatric viral infections in the UK, paediatric virology does not currently exist as a specific subspecialty. The aim of the present article was to present the existing educational platforms and training options in paediatric virology in the UK available to trainees wanting to pursue a clinical and/or academic career in paediatric virology.

Respiratory syncytial virus (RSV) is a major cause of severe respiratory tract infection worldwide. but tThere is a monoclonal antibody, palivizumab, which can be used for prophylaxis, butis no licensed vaccine or clinically effective antiviral therapy. The development of an effective vaccine has been hampered over the last 50 years by a medical disastersignificant difficulties in the 1960s in which a formalin-inactivated vaccine led to increased severity of RSV disease following acquisition of the virus in the RSV season after vaccination. However, renewed efforts to develop a vaccine have resulted in up to 445 candidate vaccines and monoclonal antibodies now being in pre-clinical or clinical development (as of December 2018April 2019). The target populations for effective vaccination are varied and include neonates, young children, pregnant women and older adults. The reasons for susceptibility to infection in each of these groups may be different and could therefore require different vaccine types for induction of protective responses, adding a further challenge for vaccine development. Here we review the current knowledge of vaccine development for these target populations, and we propose a view of the priorities for RSV vaccines and their rationale.

Viral respiratory tract infections are the most common infections of childhood. They result in clinical syndromes ranging from mild upper respiratory tract infection to severe lower respiratory tract disease requiring intensive care. Respiratory viruses are most commonly identified from a respiratory swab or nasopharyngeal aspirate by real-time PCR, which has a very high sensitivity and specificity. In this article, we review when and how children should be tested for viral respiratory tract infections and how to interpret the result in context of the clinical picture.

This is the peer reviewed version of the following article: Predicting healthcare outcomes in prematurely born infants using cluster analysis, which has been published in final form at https://doi.org/10.1002/ppul.24050. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. © 2018 Wiley Periodicals, Inc. Aims: Prematurely born infants are at high risk of respiratory morbidity following neonatal unit discharge, though prediction of outcomes is challenging. We have tested the hypothesis that cluster analysis would identify discrete groups of prematurely born infants with differing respiratory outcomes during infancy. Methods: A total of 168 infants (median (IQR) gestational age 33 (31-34) weeks) were recruited in the neonatal period from consecutive births in a tertiary neonatal unit. The baseline characteristics of the infants were used to classify them into hierarchical agglomerative clusters. Rates of viral lower respiratory tract infections (LRTIs) were recorded for 151 infants in the first year after birth. Results: Infants could be classified according to birth weight and duration of neonatal invasive mechanical ventilation (MV) into three clusters. Cluster one (MV ≤5 days) had few LRTIs. Clusters two and three (both MV ≥6 days, but BW ≥or

In children with a ventriculoperitoneal (VP) shunt in situ, is shunt externalisation of the abdominal portion mandatory in acute appendicitis? A boy aged 8 years with a long-term VP shunt presented to the emergency department with right iliac fossa pain, nausea and vomiting. Abdominal ultrasound showed likely appendicitis. We wondered whether, in a child with a VP shunt in situ with appendicitis, the shunt should always be removed and what antibiotic regimen should be used? PubMed: ‘ventriculoperitoneal’ AND ‘shunt’ AND ‘appendicitis’ OR ‘peritonitis’ Returned 89 results—of these 6 were relevant to our question. Other articles were excluded as they focused on bowel pathologies other than appendicitis, only included patients with primary VP shunt problems and were evaluating different surgical techniques. This systematic review demonstrates there are only a limited number of cases reported …

Rhinoviruses (RV) are ubiquitous respiratory tract pathogens. They affect both the upper and lower respiratory tract and cause colds but have also been associated with wheezing, asthma exacerbations and pneumonia. New blood transcription profiling techniques of the host immune response are becoming available to characterise the pathogenesis of RV in humans. This review will outline the clinical impact of RVs in children.

Respiratory syncytial virus (RSV) causes infection throughout life, with infants, adults who are severely immunocompromised, and the elderly at special risk of developing lower respiratory tract disease, hospitalisation, and death. The burden of severe disease in the elderly is comparable to seasonal influenza, and there remains no effective anti-viral drugs or vaccine for any target population. The development of a vaccine to confer immunity against severe disease is a major global health priority. A multitude of safe and immunogenic vaccine candidates have failed to induce the protective immunity needed for licensure, and in recent years this has included the largest clinical trials of RSV vaccines in history. The obstacles to vaccine development in elderly populations include an incomplete understanding of the immune responses needed for protection, the effect of aging on induction and maintenance of immunity (natural and vaccine induced immunity), and the high rate of co-morbid disease in older adults. Recent advances in structural biology, new biological platforms for antigen delivery, and insights from experimental challenge models mark the latest developments in over 50 years of research. This continues to be an active and evolving field of scientific discovery with renewed hope for a vaccine in the future.

Diagnostic challenges combined with the vulnerability of neonates to develop invasive candidiasis (IC) may lead to antifungal administration in the absence of IC. A modified point-prevalence study was performed to obtain an improved insight and understanding of antifungal prescribing in this specific patient population.Neonates and infants ≤90 days of age receiving systemic antifungals from 12 centers in England were included. Data were collected prospectively during 26 consecutive weeks and entered into an online REDCap database.Two hundred eighty neonates and infants were included, the majority ≤1 month of age (68.2%). Prematurity was the commonest underlying condition (68.9%). Antifungals were prescribed for prophylactic reason in 79.6%; of those, 64.6% and 76.3% were extreme low birth weight infants and prematurely born neonates, respectively. Additional risk factors were present in almost all patients, but only 44.7% had ≥3 risk factors rendering them more susceptible to develop IC. Nonpremature and non extremely low birth weight premature infants only scored ≥3 risk factors in 32.6% and 15%, respectively. Fluconazole was the most common antifungal used (76.7% of all prescriptions), and commonly underdosed as treatment. The number of microbiologic proven IC was low, 5.4%.Neonatal antifungal prophylaxis is commonly prescribed outside the recommendations based on known risk profiles. Fluconazole is the main antifungal prescribed in neonates and infants, with underdosing frequently observed when prescribed for treatment. Number of proven IC was very low. These observations should be taken into consideration to develop a national pediatric Antifungal Stewardship program aiming to guide rational prescribing.

Background: Follow-up studies of infants born prematurely are essential to understand the long-term consequences of preterm birth and the efficacy of interventions delivered in the neonatal period. Retention of participants for follow up studies, however, is challenging, with attrition rates of up to 70%. Our aim was to examine retention rates in two follow-up studies of prematurely born children and identify participant or study characteristics that were associated with higher attrition, and to discuss retention strategies with regard to the literature. Methods: Data from children recruited at birth to one of two studies of prematurely born infants were assessed. The two studies were the United Kingdom Oscillation Study (UKOS, a randomised study comparing two modes of neonatal ventilation in infants born less than 29weeks of gestational age (GA)), and an observational study examining the impact of viral lower respiratory tract infections in infancy in those born less than 36weeks of GA (virus study). The UKOS participants, but not those in the virus study, had regularly been contacted throughout the follow-up period. UKOS subjects were followed up at 11 to 14years of age and subjects in the virus study at 5–7 years of age. At follow up in both studies, pulmonary function and respiratory morbidity were assessed. Retention rates to follow-up in the two studies and baseline characteristics of those who were and were not retained were assessed. Results: Retention was significantly higher in UKOS than the virus study (61% versus 35%, p

RSV infection is typically associated with secondary bacterial infection. We hypothesise that the local airway immune response to RSV has incidental antibacterial effects. Using coordinated proteomics and metagenomics analysis we simultaneously analysed the microbiota and proteomes of the upper airway and determined direct antibacterial activity in airway secretions of RSV-infected children. Here, we report that the airway abundance of Streptococcus was higher in samples collected at the time of RSV infection compared with samples collected one month later. RSV infection is associated with neutrophil influx into the airway and degranulation and is marked by overexpression of proteins with known antibacterial activity including BPI, EPX, MPO and AZU1. Airway secretions of children infected with RSV, have significantly greater antibacterial activity compared to RSV-negative controls. This RSV-associated, neutrophil-mediated antibacterial response in the airway appears to act as a regulatory mechanism that modulates bacterial growth in the airways of RSV-infected children.

RSV infection is typically associated with secondary bacterial infection. We hypothesise that the local airway immune response to RSV has incidental antibacterial effects. Using coordinated proteomics and metagenomics analysis we simultaneously analysed the microbiota and proteomes of the upper airway and determined direct antibacterial activity in airway secretions of RSV-infected children. Here, we report that the airway abundance of Streptococcus was higher in samples collected at the time of RSV infection compared with samples collected one month later. RSV infection is associated with neutrophil influx into the airway and degranulation and is marked by overexpression of proteins with known antibacterial activity including BPI, EPX, MPO and AZU1. Airway secretions of children infected with RSV, have significantly greater antibacterial activity compared to RSV-negative controls. This RSV-associated, neutrophil-mediated antibacterial response in the airway appears to act as a regulatory mechanism that modulates bacterial growth in the airways of RSV-infected children., Respiratory syncytial virus (RSV) can trigger secondary airway bacterial infections. Here, by proteomics and metagenomics analyses of samples from Kenyan children, the authors report that RSV associates with Streptococcus burden and a local upper airway response with direct antibacterial properties.

Highlights • The number of cases per month were highest from November to May. • A respiratory-based primary diagnosis was the most common. • Requirements included ventilation, inotropes, renal replacement and ECMO. • Mean (SD) mortality risk was 4.8 (6.4)%, with a median (range) of 2.7 (0.2–39.1)%. • The total cost of PICU admissions was estimated to be £2,256,823 - £3,997,823., Background Human metapneumovirus (HMPV) is a pneumovirus known to cause respiratory disease in children. It was identified as a pathogen in 2001 and its healthcare burden and associated costs are not fully understood. Objectives This study aimed to assess the clinical characteristics of children with HMPV infection admitted to paediatric intensive care units (PICUs) across the United Kingdom (UK) over a nine-year period and to estimate the associated costs of care. Study design Data were collected from the UK paediatric intensive care audit network (PICANet) and costs calculated using the National Health Service (NHS) reference costing scheme. Results There were 114 admissions in which HMPV was detected. The number of admissions associated with a code of HMPV rose steadily over the study period (three in 2006 to 28 in 2014) and showed significant seasonal variability, with the peak season being from November to May. Children required varying levels of intensive care support from minimal to complex support including invasive ventilation, inotropes, renal replacement therapy and extracorporeal membrane oxygenation (ECMO). HMPV was associated with five deaths during the study period. The associated costs of PICU admissions were estimated to be between £2,256,823 and £3,997,823 over the study period, with estimated annual costs rising over the study period due to increasing HMPV admissions. Conclusions HMPV is associated with a significant healthcare burden and associated cost of care in PICUs in the UK.

Background Viral bronchiolitis is one of the most common causes of hospitalisation in young infants. It has previously been shown that many United Kingdom (UK) hospital Trusts were not compliant with many aspects of the National Institute for Health and Care Excellence (NICE) bronchiolitis guideline prior to its publication. Objectives This study aimed to investigate changes in the management of bronchiolitis by hospital Trusts between 2015 (before NICE guideline publication) and 2017, after publication. Study design We prospectively surveyed paediatricians at UK hospital Trusts on the management of bronchiolitis before (March to May 2015) and after (January to May 2017) the NICE bronchiolitis guideline publication in June 2015, using an electronic, structured questionnaire. Results In 2015 111 Trusts were represented and in 2017 100 Trusts. Significant improvements were seen in the use of nebulised bronchodilators and hypertonic saline and provision of parental written guidance. However, full compliance with the guideline did not change with 18% of Trusts compliant before publication of the guideline in 2015 and 19% fully compliant with the guideline in 2017. Conclusions Overall there were modest but important improvements in the reported management of bronchiolitis after the publication of the NICE guideline.

Background Viral bronchiolitis is the leading cause of hospitalisation in infants less than a year old. The United Kingdom (UK) National Institute for Health and Care Excellence (NICE) published a guideline for the management of viral bronchiolitis in June 2015. Objectives This study aimed to prospectively survey the management of viral bronchiolitis in hospital Trusts in the UK to provide a baseline of practice prior to the publication of the 2015 NICE bronchiolitis guideline against which future practice can be assessed. Study design An electronic, structured questionnaire was sent to hospital paediatricians in the UK prior to the publication of the NICE bronchiolitis guideline via the Royal College of Paediatrics and Child Health e-portfolio system to assess the quality of Trust’s viral bronchiolitis management guidelines. Results Paediatricians from 111 (65% of all) UK Trusts completed an electronic questionnaire. 91% of Trusts had a bronchiolitis guideline. Overall only 18% of Trusts would be fully compliant with the NICE guideline. Between 43–100% of Trusts would be compliant with different sections of the guideline. There was variation in hospital admission criteria with respect to the need for supplemental oxygen (oxygen saturations Conclusions There was wide variation in the management of infants with bronchiolitis in Trusts. Most bronchiolitic infants are not managed optimally in hospitals. Future guidelines should include advice on virus testing and isolation/cohorting.

Respiratory syncytial virus (RSV) is the second most common cause of mortality in infants worldwide after malaria and the leading cause of hospitalisation in infants in many countries. It is also associated with high levels of morbidity and mortality in older adults (those over 60 years of age). These high levels of healthcare utilisation result in huge associated healthcare costs. As such the development of an RSV vaccine is listed as a leading global priority by the World Health Organisation (WHO). There is a monoclonal antibody (palivizumab) licensed to prevent RSV infection, but it is only used in high income countries for the most high-risk infants due to its very high cost. The development of an RSV vaccine/prophylactic agent has been hampered by an incomplete understanding of the immunopathogenesis of RSV infection, although many are currently undergoing clinical trials. Adding a new vaccine to existing vaccine schedules will also present many challenges.

Respiratory syncytial virus (RSV) infection is the most important cause of hospitalization in infants and is one of the leading global causes of infant mortality and as such its prevention through vaccination is a public health priority. While essential for the successful implementation of vaccine programs, there remains a paucity of data on the epidemiology of the virus in different settings and age groups and limited knowledge about virus transmission and the health-care costs of the disease. Such data are now needed to populate health economic models and to inform optimal approaches to disease control through vaccination.

The aim of this study was to investigate changes in general practitioner (GP) management before and after the publication of the National Institute for Health and Care Excellence bronchiolitis guideline. In March 2015 and May 2016, an electronic questionnaire was sent to GPs. It was completed by 1001 GPs in 2015 and 1009 in 2016. There were small but significant improvements in proportions of GPs using a guideline, measuring oxygen saturations and providing written guidance, and appropriate reductions in those prescribing medications. Thirty-five per cent had read the guideline and 25% changed their practice since guideline publication. There were modest but significant improvements in reported management by GPs after guideline publication.

Objectives To determine the impact of viral lower respiratory tract infections (LRTIs) in infancy including rhinovirus (RV) and infancy respiratory syncytial virus (RSV), on school age pulmonary function and healthcare utilization in prematurely born children. Working hypothesis School age respiratory outcomes would be worse and healthcare utilization greater in children who had viral LRTIs in infancy. Study design Prospective study. Subject selection A cohort of prematurely born children who had symptomatic LRTIs during infancy documented, was recalled. Methods Pulmonary function was assessed at 5 to 7 years of age and health related costs of care from aged one to follow‐up determined. Results Fifty‐one children, median gestational age 33+6 weeks, were assessed at a median (IQR) age 7.03 (6.37–7.26) years. Twenty‐one children had no LRTI, 14 RV LRTI, 10 RSV LRTI, and 6 another viral LRTI (other LRTI). Compared to the no LRTI group, the RV group had a lower FEV1 (P = 0.033) and the other LRTI group a lower FVC (P = 0.006). Non‐respiratory medication costs were higher in the RV (P = 0.018) and RSV (P = 0.013) groups. Overall respiratory healthcare costs in the RV (£153/year) and RSV (£27/year) groups did not differ significantly from the no LRTI group (£56/year); the other LRTI group (£431/year) had higher respiratory healthcare costs (P = 0.042). Conclusions In moderately prematurely born children, RV and RSV LRTIs in infancy were not associated with higher respiratory healthcare costs after infancy. Children who experienced LRTIs caused by other respiratory viruses (including RV) had higher respiratory healthcare costs and greater pulmonary function impairment.

© Copyright 2017, Mary Ann Liebert, Inc. 2017. Viral bronchiolitis is the leading cause of hospitalization in infants in the United Kingdom (UK) with wide variation in rates of hospitalization in different geographical regions of the UK. A potential cause of these differences is variation in primary care management and referral to hospital. This study aimed to prospectively survey general practitioners (GPs) in the UK to provide a benchmark of practice against which future practice can be assessed. An electronic, structured questionnaire was sent to 1,001 geographically representative GPs in primary care centers in the UK, through the market research company MedeConnect, to assess their management of infants with viral bronchiolitis. We measured practice before the 2015 National Institute for Health and Care Excellence (NICE) bronchiolitis guideline against the guideline, to obtain a benchmark of practice. We also used a multivariate analysis to assess GP factors associated with variation in management. Thirty-nine percent of GPs did not refer to any guideline to manage infants with bronchiolitis, 33% did not routinely measure oxygen saturations, 48% prescribed an "inappropriate" (evidence of no benefit) medication, and 62% did not give written guidance to parents. GP factors influencing management included the year the GP qualified, sex, region of practice, and working at a dispensing practice. Up to 75% of GPs' management did not conform to the newly published 2015 NICE bronchiolitis guideline before its publication. There was wide variation in the management of infants with viral bronchiolitis by UK GPs. Most infants with viral bronchiolitis are not managed optimally by GPs and multiple GP factors influenced this management.

Aims Infants born prematurely are at increased risk of RSV lower respiratory tract infection (LRTI) and its consequences. We aimed to determine which prematurely born infants were at risk of rhinovirus (RV) LRTI and whether their outcomes differed according to risk factors. Methods Birth weight, gestational age, duration of mechanical ventilation and supplemental oxygen and functional residual capacity and respiratory system compliance and resistance measured at 36 weeks postmenstrual age in 168 prematurely born infants were used to classify them into clusters using hierarchical agglomerative clustering with the Euclidean distance metric. All LRTIs in the first year after birth (in hospital or the community) were recorded and their NPAs were tested for 13 respiratory viruses. Fifty-six children were followed up at a median (IQR) age of 7.0 (6.4–7.3) years and healthcare utilisation costs from age one to the point of follow-up were determined. Results The infants could be classified with 100% accuracy into three clusters. Cluster three compared with Cluster two and Cluster two compared with Cluster one were of significantly lower gestational age, birthweight, had a longer duration of mechanical ventilation and supplemental oxygen and had worse lung function at 36 weeks PMA At one year of age, Cluster three had had a higher incidence of RV LRTI (p At school age, healthcare utilisation costs for respiratory (p=0.008) and non-respiratory (p=0.003) causes were higher in Clusters two and three than in Cluster one (see Table). Conclusion Extremely prematurely born infants who require prolonged ventilation and have poorer premorbid lung function are at increased risk of RV LRTIs and have higher healthcare utilisation costs even at school age.