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ObjectiveTo describe the impact of the SARS-CoV-2 pandemic on the incidence of paediatric viral respiratory tract infection in Oxfordshire, UK.MethodsData on paediatric Emergency Department (ED) attendances (0-15 years inclusive), respiratory virus testing, vital signs and mortality at Oxford University Hospitals were summarised using descriptive statistics.ResultsBetween 1-March-2016 and 30-July-2021, 155,056 ED attendances occurred and 7,195 respiratory virus PCRs were performed. Detection of all pathogens was suppressed during the first national lockdown. Rhinovirus and adenovirus rates increased when schools reopened September-December 2020, then fell, before rising in March-May 2021. The usual winter RSV peak did not occur in 2020/21, with an inter-seasonal rise (32/1,000 attendances in 0-3yr olds) in July 2021. Influenza remained suppressed throughout. A higher Paediatric Early Warning Score (PEWS) was seen for attendees with adenovirus during the pandemic compared to pre-pandemic (p=0.04, Mann-Witney U test), no other differences in PEWS were seen.ConclusionsSARS-CoV-2 caused major changes in the incidence of paediatric respiratory viral infection in Oxfordshire, with implications for clinical service demand, testing strategies, timing of palivizumab RSV prophylaxis, and highlighting the need to understand which public health interventions are most effective for preventing respiratory virus infections.

ObjectivesGram-negative organisms are common causes of bloodstream infection (BSI) during the neonatal period and early childhood. Whilst several large studies have characterised these isolates in adults, equivalent data (particularly incorporating whole genome sequencing) is lacking in the paediatric population.MethodsWe performed an epidemiological and sequencing based analysis of Gram-negative bloodstream infections in children Results327 isolates (296 successfully sequenced) from 287 patients were included. The burden of infection was predominantly in neonates (124/327[38%]). Most infections were caused by Escherichia coli (149/327[46%])/Klebsiella spp. (69/327[21%]) and Enterobacter hormaechei (34/327[10%]). There was no evidence of an increasing incidence of E. coli BSIs (IRRy 0.96, 95%CI 0.90-1.30, p=0.30) and for Klebsiella spp. there was some evidence that the incidence decreased slightly (IRRy 0.91, 95%CI 0.83-1.00, p=0.06). Similarly the proportion of antimicrobial resistant (across all antimicrobial classes evaluated) isolates did not change over time, though we did identify some evidence of sub-breakpoint increases in gentamicin resistance IRRy 1.86, 95%CI 1.33-2.58, pheterogeneity=0.002. The population structure of E. coli BSI isolates in neonates and children mirrors that in adults with a predominance of STs 131/95/73/69 and the same proportion of O-antigen serotypes covered by the ExPEC-4V vaccine. In most cases there was no evidence of transmission/point-source acquisition and whole genome sequencing was able to refute a previously suspected Serratia marcescens outbreak.ConclusionOur findings support continued use of current empirical treatment guidelines and suggest that O-antigen targeted vaccines may have a role in reducing the incidence of neonatal sepsis.

Exanthems/rashes are common in childhood and account for a large number of consultations in primary care and attendances to the emergency department. They are typically caused by allergic reactions, by viruses and occasionally by severe life-threatening bacterial infections. A careful history (including prodrome, associated symptoms, exposure to infectious contact, foreign travel, animals and immunization status), examination of the rash (including distribution, morphology, nature and site) and generalized examination (including presence of conjunctivitis, genital lesions, enanthems, hepatosplenomegaly and lymphadenopathy) can inform diagnosis. Molecular testing has led to a cause being identified in approximately 50% of cases. Early diagnosis is particularly important in the context of severe systemic infection, in immunocompromised hosts and in pregnancy. This review outlines the most common infectious exanthems, including measles, rubella, varicella, erythema infectiosum, roseola infantum and enterovirus infection.

We describe the youngest case to date of a 2 year old child who developed central skull base osteomyelitis (SBO) initially presenting with a fever, vomiting and sore throat. An extremely rare complication of mastoiditis following otitis media in children is SBO which can present with non-specific symptoms. This report describes the first case of symptomatic ischaemic stroke secondary to SBO in an immunocompetent child. We review the literature of the management and the potential cerebrovascular complications of central SBO in children secondary to otolaryngological infection.

A 28-month-old infant presented with fever, vomiting and encephalopathy. Magnetic resonance imaging findings and family history confirmed a diagnosis of recurrent familial acute necrotizing encephalopathy (ANE1). We believe that this is the first description implicating the H1N1 viral strain as a trigger and the second report of a T653I mutation in the RANBP2 gene described in relation to ANE1.

Skull base osteomyelitis is a rare condition in childhood and can be described according to whether it is associated with spread of infection from the middle ear (otogenic) or not (nonotogenic). Early recognition of this serious disease and prompt treatment are key to preventing extension to adjacent vascular and nervous system structures. Diagnosis can be challenging due to the variable presentation of the disease and potentially subtle radiological appearances. We present 2 cases of nonotogenic skull base osteomyelitis in childhood both affecting the clivus and review the 6 cases previously described. Both children presented with fever, headache and neck stiffness and responded well to medical management alone; detailed imaging was key to making a diagnosis.

This is a retrospective case review of patients presenting with periodic fevers to the paediatric infectious disease clinic at the Children’s Hospital, Oxford, over a ten year period.

INTRODUCTION: Streptococcus pneumoniae remains a major global health problem and a leading cause of death in children worldwide. The factors that influence development of pneumococcal sepsis remain poorly understood, although increasing evidence points towards a role for genetic variation in the host's immune response. Recent insights from the study of animal models, rare human primary immunodeficiency states, and population-based genetic epidemiology have focused attention on the role of the proinflammatory transcription factor NF-κB in pneumococcal disease pathogenesis. The possible role of genetic variation in the atypical NF-κB inhibitor IκB-R, encoded by NFKBIL2, in susceptibility to invasive pneumococcal disease has not, to our knowledge, previously been reported upon. METHODS: An association study was performed examining the frequencies of nine common NFKBIL2 polymorphisms in two invasive pneumococcal disease case-control groups: European individuals from hospitals in Oxfordshire, UK (275 patients and 733 controls), and African individuals from Kilifi District Hospital, Kenya (687 patients with bacteraemia, of which 173 patients had pneumococcal disease, together with 550 controls). RESULTS: Five polymorphisms significantly associated with invasive pneumococcal disease susceptibility in the European study, of which two polymorphisms also associated with disease in African individuals. Heterozygosity at these loci was associated with protection from invasive pneumococcal disease (rs760477, Mantel-Haenszel 2 × 2 χ(2) = 11.797, P = 0.0006, odds ratio = 0.67, 95% confidence interval = 0.53 to 0.84; rs4925858, Mantel-Haenszel 2 × 2 χ(2) = 9.104, P = 0.003, odds ratio = 0.70, 95% confidence interval = 0.55 to 0.88). Linkage disequilibrium was more extensive in European individuals than in Kenyans. CONCLUSIONS: Common NFKBIL2 polymorphisms are associated with susceptibility to invasive pneumococcal disease in European and African populations. These findings further highlight the importance of control of NF-κB in host defence against pneumococcal disease.

Infectious diseases precipitate the majority of acute medical admissions to the pediatric intensive care unit (PICU) despite the availability of a wide variety of antimicrobial agents. In previously healthy children, specific therapy is likely to have only a minimal impact on the continuing severity of the disease, since it is usually the host response to the infection that determines progression, and strategies that avoid admission are clearly preferable. Prophylactic immunization offers the potential for prevention of PICU admission for many of the major pathogens affecting children. Indeed, vaccines already exist for many of the causes of the major infectious syndromes presenting to PICU (Table 5.1).

RATIONALE: Increasing evidence supports a key role for the transcription factor nuclear factor (NF)-kappaB in the host response to pneumococcal infection. Control of NF-kappaB activity is achieved through interactions with the IkappaB family of inhibitors, encoded by the genes NFKBIA, NFKBIB, and NFKBIE. Rare NFKBIA mutations cause immunodeficiency with severe bacterial infection, raising the possibility that common IkappaB gene polymorphisms confer susceptibility to common bacterial disease. OBJECTIVES: To determine whether polymorphisms in NFKBIA, NFKBIB, and NFKBIE associate with susceptibility to invasive pneumococcal disease (IPD) and thoracic empyema. METHODS: We studied the frequencies of 62 single-nucleotide polymorphisms (SNPs) across NFKBIA, NFKBIB, and NFKBIE in individuals with IPD and control subjects (n=1,060). Significantly associated SNPs were then studied in a group of individuals with thoracic empyema and a second control group (n=632). MEASUREMENTS AND MAIN RESULTS: Two SNPs in the NFKBIA promoter region were associated with protection from IPD in both the initial study group and the pneumococcal empyema subgroup. Significant protection from IPD was observed for carriage of mutant alleles at these two loci on combining the groups (SNP rs3138053: Mantel-Haenszel 2x2 chi2=13.030, p=0.0003; odds ratio [OR], 0.60; 95% confidence interval [CI], 0.45-0.79; rs2233406: Mantel-Haenszel 2x2 chi2=18.927, p=0.00001; OR, 0.55; 95% CI, 0.42-0.72). An NFKBIE SNP associated with susceptibility to IPD but not pneumococcal empyema. None of the NFKBIB SNPs associated with IPD susceptibility. CONCLUSIONS: NFKBIA polymorphisms associate with susceptibility to IPD. Genetic variation in an inhibitor of NF-kappaB therefore not only causes a very rare immunodeficiency state but may also influence the development of common infectious disease.