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We investigated a secondary school (11–16 year-olds), a primary school (5–11 year-olds), reception year (4–5 year-olds) and a nursery (2–5 year-olds) following confirmed monkeypox in an adult in each educational setting during June and July 2022. MVA-BN vaccine was offered up to 14 days post exposure to 186 children

Use of artificial intelligence (AI) is a burgeoning field in otolaryngology and the communication sciences. A virtual symposium on the topic was convened from Duke University on October 26, 2020, and was attended by more than 170 participants worldwide. This review presents summaries of all but one of the talks presented during the symposium; recordings of all the talks, along with the discussions for the talks, are available at https://www.youtube.com/watch?v=ktfewrXvEFg and https://www.youtube.com/watch?v=-gQ5qX2v3rg . Each of the summaries is about 2500 words in length and each summary includes two figures. This level of detail far exceeds the brief summaries presented in traditional reviews and thus provides a more-informed glimpse into the power and diversity of current AI applications in otolaryngology and the communication sciences and how to harness that power for future applications.

Little is known about the MIS-C risk with different SARS-CoV-2 variants. In Southeast England, MIS-C rates per confirmed SARS-CoV-2 infections in 0-16 years-olds were 56% lower (rate ratio, 0.34; 95%CI, 0.23-0.50) during pre-vaccine Delta, 66% lower (0.44; 0.28-0.69) during post-vaccine Delta and 95% lower (0.05; 0.02-0.10) during the Omicron period.

T1 Figure 1ConclusionsOverall, this largest paediatric single cell COVID-19 study to date showed significant differences in response to SARS-CoV-2 between children and adults, reflecting the changes of the immune landscape over developmental time, which in children are dominated by naive and innate responses.

Objective Tuberculosis (TB) can affect young children, resulting in serious disease at a young age or reactivation later in life. Identifying cases of latent TB infection (LTBI) in children exposed to active cases is important to prevent morbidity and mortality. There is currently limited guidance on appropriate testing methods in situations involving mass screening of children in low TB incidence settings such as England. This study describes case reports of two separate occasions in which nursery-age children in England underwent LTBI screening and explores the decisions involved in choosing the most appropriate test and screening process. Methods A literature search, review of health protection case and incident management notes, and interviews with key stakeholders were conducted. Results Two different tests—tuberculin skin testing and interferon gamma release assay—were used in each respective screening situation and the decision between the two was taken based on cohort, organizational, and index case risk factors. Screening took place in dedicated secondary care clinics. No cases of LTBI were identified from either screening incident. Conclusion Our study highlights the lack of definitive guidance for mass LTBI screening of young children and presents the approaches to decision making that can be adopted by others. Further research is required to test the approach suggested in this article and to ensure that evidence-based national guidance provides a consistent and effective approach to such incidents.

While a substantial proportion of adults infected with SARS-CoV-2 progress to develop severe disease, children rarely manifest respiratory complications. Therefore, understanding differences in the local and systemic response to SARS-CoV-2 infection between children and adults may provide important clues about the pathogenesis of SARS-CoV-2 infection. To address this, we first generated a healthy reference multi-omics single cell data set from children (n=30) in whom we have profiled triple matched samples: nasal and tracheal brushings and PBMCs, where we track the developmental changes for 42 airway and 31 blood cell populations from infancy, through childhood to adolescence. This has revealed the presence of naive B and T lymphocytes in neonates and infants with a unique gene expression signature bearing hallmarks of innate immunity. We then contrast the healthy reference with equivalent data from severe paediatric and adult COVID-19 patients (total n=27), from the same three types of samples: upper and lower airways and blood. We found striking differences: children with COVID-19 as opposed to adults had a higher proportion of innate lymphoid and non-clonally expanded naive T cells in peripheral blood, and a limited interferon-response signature. In the airway epithelium, we found the highest viral load in goblet and ciliated cells and describe a novel inflammatory epithelial cell population. These cells represent a transitional regenerative state between secretory and ciliated cells; they were found in healthy children and were enriched in paediatric and adult COVID-19 patients. Epithelial cells display an antiviral and neutrophil-recruiting gene signature that is weaker in severe paediatricversusadult COVID-19. Our matched blood and airway samples allowed us to study the spatial dynamics of infection. Lastly, we provide a user-friendly interface for this data1as a highly granular reference for the study of immune responses in airways and blood in children.

Children and adolescents represent an important component of the overall tuberculosis (TB) epidemic. Following exposure to an infectious case of TB and subsequent infection, young children and pubertal adolescents have a high risk of progression to TB disease. The disease manifestations change with age; the youngest children often have paucibacillary disease, either localised to lymph nodes or disseminated through the body as miliary TB or TB meningitis. As children enter adolescence, they are more likely to develop multibacillary disease and have typical features of adult TB, such as cavities. The diagnosis of TB in young children can be challenging, and microbiological confirmation is frequently not possible, due to the paucibacillary nature of the disease as well as the challenges in obtaining respiratory specimens. The clinician must therefore assemble pieces of evidence to support the diagnosis, including symptoms, signs, immunological tests, and radiology. The treatment of TB infection and disease in children and adolescents are broadly similar to adults. However, important differences include drug dosages, the need for child-friendly formulations, specific issues for adherence support and other areas such as impact on schooling, and child protection. Childhood TB needs to be addressed as part of any TB programme and services need to be tailored to the specific needs of children and adolescents of all ages. If this is undertaken, the potential for a future TB-free generation is possible.

Aims The meaningful health needs of unaccompanied asylum-seeking children (UASC) are poorly understood, preventing a fully informed population-based approach to planning health services. This lack of data around UASC has been identified as an unmet research need, as well as a rights of the child issue. Here we describe the physical, sexual and emotional health needs of a population of UASC presenting to a London borough. Methods Unlinked data were collected for UASC presenting to a London borough between January 2016 and March 2019, including data from initial health assessment (IHA) and infectious diseases (ID) screening. Results During the study period 101 UASC were seen for IHA (84% male, age range 14–17, median age 16). Countries of origin included Eritrea (27%), Sudan (14%) and Ethiopia (12%). Two thirds of UASC disclosed historical physical assault/abuse including 16% who described experience of torture. On examination more than half, 54%, of UASC had scars consistent with their disclosures, and 9% had evidence of harmful traditional practices such as FGM, uvulectomy and scarification. Historical sexual assault or abuse was disclosed by 13% UASC, including 6 of the 16 (38%) female UASC. A further six UASC (6%) reported witnessing sexual assault. For 6/16 (38%) female UASC, there was evidence of trafficking and suspicion of undisclosed sexual assault/abuse. The majority, 77% of UASC demonstrated symptoms of poor mental health including sleep problems and signs of trauma. Deliberate self-harm and parasuicide were reported at some point in 8% UASC. Data are available for ID screening of 69 UASC from the same borough during the study period, of whom 28/69 (41%) had one positive ID result requiring treatment and 9/69 (13%) had two or more results requiring treatment. Diagnoses included latent TB (25%), schistosomiasis (13%) and other helminth infections (9%), and hepatitis B (6%). Conclusion This cohort demonstrate high rates of trauma, physical and sexual abuse and unmet physical and mental health needs. This population require intensive, integrated support and health services to optimise engagement and physical health, mental health and social outcomes.

Aims To assess our strategy for diagnosing schistosomiasis in unaccompanied child refugees in the UK. Schistosomiasis is an easily treatable infection with significant risk of long term complications if not treated. Methods A retrospective analysis of a prospectively collected database of a health screening clinic for unaccompanied child refugees. Urinalysis, stool microscopy and full blood count with serum save are performed for all refugee young people attending our clinic. Schistosomiasis serology is requested if microscopic haematuria or eosinophilia are found and stool and urine are negative for ova. Schistosomiasis is diagnosed on positive serology or stool/urine microscopy positive for ova. Treatment is single dose praziquantel. Our incidence of diagnosed schistosomiasis is compared to published country prevalence data. Results 232 unaccompanied refugees age 16–18 years (median 17 years) were assessed. 44/232 had eosinophilia >0.4 × 109/L (range 0.4–2.02 × 109/L). Of these 9 had stool positive for S.Mansoni ova, 7 had serum-positive schistosomiasis, 12 had other parasites diagnosed on stool microscopy and 16 tested negative. 20/232 had microscopic haematuria on urinalysis. Only 1/20 had S.Haematobium ova on microscopy. One had negative microscopy but had eosinophilia and serum-positive schistosomiasis. 17/217(7.8%) patients who provided stool samples tested positive for S.Mansoni ova, 8/17 did not have eosinophilia. Therefore a total of 25(10.7%) young refugees (24 male, 1 female) tested positive for schistosomiasis: 1 on urine microscopy, 17 on stool and 7 on serology. Countries of origin were Eritrea (10), Sudan (9) and Ethiopia (6). 10/63 (15%) of Eritrean refugees tested positive, 9/41 (22%) of Sudanese refugees and 6/26 (23%) of Ethiopian refugees. Published country population prevalences of schistosomiasis are 41% for Eritrea and 34% for Sudan. One further Eritrean patient who had normal stool, urine and eosinophils and was discharged, subsequently attended a Tropical Medicine clinic and tested serum-positive for schistosomiasis. Conclusion We are diagnosing significant rates of schistosomiasis. However, the higher published prevalences for the countries of origin suggest cases may be being missed with our current screening method which relies heavily on eosinophilia and microscopy. Our screening strategy will therefore be adjusted to include schistosomiasis serology on all young refugees from sub-Saharan Africa. We will prospectively assess the impact of this on our diagnosis rate.

We aimed to evaluate a screening programme for infection in unaccompanied asylum seeking children and young people against national guidance and to described the rates of identified infection in the cohort. The audit was conducted by retrospective case note review of routinely collected, anonymised patient data from all UASC referred between January 2016 and December 2018 in two paediatric infectious diseases clinics.There were 252 individuals from 19 countries included in the study, of these 88% were male, and the median age was 17 years (range 11–18). Individuals from Afghanistan, Eritrea and Albania constituted the majority of those seen. Median time between arriving in the UK and infection screening was 6 months (IQR 4–10 months, data available on 197 UASC). There were 94% (238/252) of cases tested for tuberculosis (TB), of whom 23% (55/238) were positive, including three young people with TB disease. Of those tested for hepatitis B, 4.8% (10/210) were positive, 0.5% (1/121) were positive for hepatitis C and of 252 tested, none were positive for HIV. Of the 163 individuals who were tested for schistosomiasis, 27 were positive (16%).The majority of patients were appropriately tested for infections with a high rate of identification of treatable asymptomatic infection. Infections were of both individual and public health significance. Our findings of clinically significant rates of treatable infections in UASC highlight the importance of infection screening for all in this vulnerable patient group.

Aim To assess the distribution of socioeconomic status across different subspecialty outpatient clinics in a large paediatric service. Methods 32,369 consecutive, accepted, new referrals to selected paediatric clinics at a large London hospital from April 2007 to June 2018 were reviewed (Allergy, Asthma, Chronic Fatigue Syndrome/ME, Diabetes, Endocrine, Epilepsy, General Paediatrics and Rapid Access). Data collected included age, postcode, referral date, referral source, clinic code and appointment attendance. The mean Index of Multiple Deprivation rank for each postcode was obtained. The proportion of patients in the most and least deprived quintiles were also calculated. 229 postcodes were unmatched. Results Conclusions The socioeconomic profile of secondary care clinics for Allergy, Epilepsy and General Paediatrics broadly matched the profile of our hospital inpatient population (4.4% and 37.9% in the least and most deprived quintiles). Secondary care Asthma and Rapid Access clinics were slightly more skewed towards patients from more deprived areas. In contrast, Endocrine, Diabetes and CFS/ME clinics showed a much higher proportion of patients from more affluent backgrounds– perhaps reflecting a larger proportion of these patients who live outside our local area. Further research will now be conducted to determine the extent to which these findings may also reflect unmet need and difficulty in accessing more specialist clinics for families living in more deprived areas.

Background Previous research has established the relationship between socioeconomic deprivation and both emergency hospital use and General Practice use amongst Paediatric patients in the UK. To the best of our knowledge, no large-scale research has been conducted into this relationship in paediatric outpatient clinics. Aim To assess the distribution of socioeconomic status across different subspecialty outpatient clinics in a large paediatric service. Methods 32 369 consecutive, accepted, new referrals to selected paediatric clinics at a large London hospital from April 2007 to June 2018 were reviewed (Allergy, Asthma, Chronic Fatigue Syndrome/ME, Diabetes, Endocrine, Epilepsy, General Paediatrics and Rapid Access). Data collected included age, postcode, referral date, referral source, clinic code and appointment attendance. The mean Index of Multiple Deprivation rank for each postcode was obtained from The Department for Communities and Local Government. The proportion of patients in the most and least deprived quintiles were also calculated. 229 postcodes were unmatched. Results Table 1: Conclusions The socioeconomic profile of secondary care clinics for Allergy, Epilepsy and General Paediatrics broadly matched the profile of our hospital inpatient population (4.4% and 37.9% in the least and most deprived quintiles). Secondary care Asthma and Rapid Access clinics were slightly more skewed towards patients from more deprived areas. In contrast, Endocrine, Diabetes and CFS/ME clinics showed a much higher proportion of patients from more affluent backgrounds – perhaps reflecting a larger proportion of these patients who live outside our local area. Further research will now be conducted to determine the extent to which these findings may also reflect unmet need and difficulty in accessing more specialist clinics for families living in more deprived areas.

Background In 2016, 3175 unaccompanied asylum-seeking children (UASC) entered the United Kingdom. Many originate from countries with high rates of infections which are often treatable in the asymptomatic stages preventing progression to severe disease. Following statutory Initial Health Assessments (IHA), referral to specialist clinics is encouraged, where testing for latent infections may be tailored appropriately. Aims To evaluate the service provided by two infection clinics to determine if UASC infection screening was offered as recommended by Royal College Paediatrics and Child Health guidance Methods A clinical audit was registered at both sites. Data were anonymously and retrospectively extracted from patient records into a Microsoft Excel database for UASC seen between January 1 st 2016 and 30th August 2017. Results 77 UASC were seen in clinic, 91% were male, median age was 16 years (range 11–18). They came from 14 different countries; 31 were from Afghanistan, 15 from Eritrea and 10 from Albania. All were tested for TB. 51 were tested for hepatitis B, of whom four (8%) were positive. 51 UASC tested negative for HIV and hepatitis C. Of 24 children tested for schistosomiasis four (16.6%) were positive. Of 74 asymptomatic UASC, 17 (23%) had LTBI. Three UASC with active tuberculosis were referred following presentation at emergency departments, all originally from Afghanistan. Two had been symptomatic for over four months. The median length of time between arriving in the UK and infection screening was 10 months (range 1–60 months; data available on 37 children). Conclusion We demonstrate clinically important rates of detection of treatable infections. Patients were offered testing as recommended by RCPCH guidance but there was significant delay due to high non- attendance and delays in IHA Intensive liaison work by specialist Table 1: Outcomes within each domain for the Core Outcome Set (COS) during each Delphi round nurses is ongoing to improve the time to testing, with promising results. We recommend that timely and tailored infection screening be offered to all UASC, by informed consent following expert counselling about their individual risk More data are needed to inform best practice and develop consistent guidance.

ObjectiveTo assess equity of access to paediatric outpatient clinics in our hospital.Design/settingRetrospective analysis of consecutive accepted referrals to allergy, asthma, epilepsy, general paediatrics, rapid access, chronic fatigue syndrome, diabetes and endocrine outpatient clinics.Patients32 369 new patients, April 2007 to June 2018.ResultsAmong local patients (58.1%) 0.2%–2.5% of patients referred to each clinic lived in the least deprived quintile, and 43.5%–48.4% in the most deprived quintile—similar to inpatient admissions and the local population. Tertiary clinics showed a much higher proportion of patients from the least deprived quintiles (15.9%–26.2%).ConclusionsLocal outpatient referrals broadly reflected the socioeconomic distribution, although not necessarily the distribution of need, of our local population. A relatively high proportion of patients in tertiary clinics were from more affluent postcodes, highlighting the need for referral inequalities to be evaluated across networks or regions.

Streptococcus pneumoniae is a common cause of pneumonia and infective exacerbations of chronic lung disease, yet there are few data on how adaptive immunity can specifically prevent S. pneumoniae lung infection. We have used a murine model of nasopharyngeal colonization by the serotype 19F S. pneumoniae strain EF3030 followed by lung infection to investigate whether colonization protects against subsequent lung infection and the mechanisms involved. EF3030 colonization induced systemic and local immunoglobulin G against a limited number of S. pneumoniae protein antigens rather than capsular polysaccharide. During lung infection, previously colonized mice had increased early cytokine responses and neutrophil recruitment and reduced bacterial colony-forming units in the lungs and bronchoalveolar lavage fluid compared with control mice. Colonization-induced protection was lost when experiments were repeated in B-cell- or neutrophil-deficient mice. Furthermore, the improved interleukin (IL)-17 response to infection in previously colonized mice was abolished by depletion of CD4+ cells, and prior colonization did not protect against lung infection in mice depleted of CD4+ cells or IL17. Together these data show that naturally acquired protective immunity to S. pneumoniae lung infection requires both humoral and cell-mediated immune responses, providing a template for the design of improved vaccines that can specifically prevent pneumonia or acute bronchitis.

Streptococcus pneumoniae infections induce inflammatory responses that contribute toward both disease pathogenesis and immunity, but the host–pathogen interactions that mediate these effects are poorly defined. We used the surface lipoprotein-deficient ∆lgt pneumococcal mutant strain to test the hypothesis that lipoproteins are key determinants of TLR-mediated immune responses to S. pneumoniae. We show using reporter assays that TLR2 signaling is dependent on pneumococcal lipoproteins, and that macrophage NF-κB activation and TNF-α release were reduced in response to the ∆lgt strain. Differences in TNF-α responses between Δlgt and wild-type bacteria were abrogated for macrophages from TLR2- but not TLR4-deficient mice. Transcriptional profiling of human macrophages revealed attenuated TLR2-associated responses to ∆lgt S. pneumoniae, comprising many NF-κB–regulated proinflammatory cytokine and chemokine genes. Importantly, non-TLR2–associated responses were preserved. Experiments using leukocytes from IL-1R–associated kinase-4–deficient patients and a mouse pneumonia model confirmed that proinflammatory responses were lipoprotein dependent. Our data suggest that leukocyte responses to bacterial lipoproteins are required for TLR2- and IL-1R–associated kinase-4–mediated inflammatory responses to S. pneumoniae.

This case report describes an interesting use of virtual surgical planning to fabricate tooth-borne cutting guides to assist in localization and enucleation of multiple recurrent odontogenic keratocysts close to the inferior alveolar nerve. The 3-dimensional models generated and cutting guides increased the accuracy and precision of the procedure and decreased surgical time and potential patient morbidity.

TheStreptococcuspneumoniaecapsule is vital for virulence and may inhibit complement activity and phagocytosis. However, there are only limited data on the mechanisms by which the capsule affects complement and the consequences forS. pneumoniaeinteractions with phagocytes. Using unencapsulated serotype 2 and 4S. pneumoniaemutants, we have confirmed that the capsule has several effects on complement activity. The capsule impaired bacterial opsonization with C3b/iC3b by both the alternative and classical complement pathways and also inhibited conversion of C3b bound to the bacterial surface to iC3b. There was increased binding of the classical pathway mediators immunoglobulin G (IgG) and C-reactive protein (CRP) to unencapsulatedS. pneumoniae, indicating that the capsule could inhibit classical pathway complement activity by masking antibody recognition of subcapsular antigens, as well as by inhibiting CRP binding. Cleavage of serum IgG by the enzyme IdeS reduced C3b/iC3b deposition on all of the strains, but there were still marked increases in C3b/iC3b deposition on unencapsulated TIGR4 and D39 strains compared to encapsulated strains, suggesting that the capsule inhibits both IgG-mediated and IgG-independent complement activity againstS. pneumoniae. Unencapsulated strains were more susceptible to neutrophil phagocytosis after incubation in normal serum, normal serum treated with IdeS, complement-deficient serum, and complement-deficient serum treated with IdeS or in buffer alone, suggesting that the capsule inhibits phagocytosis mediated by Fcγ receptors, complement receptors, and nonopsonic receptors. Overall, these data show that theS. pneumoniaecapsule affects multiple aspects of complement- and neutrophil-mediated immunity, resulting in a profound inhibition of opsonophagocytosis.

Objectives Management of HIV-infected children with tuberculosis (TB) is challenging. The objective of this study was to assess current treatment and outcomes in a resource-rich setting in the era of highly active antiretroviral therapy (HAART). Methods A retrospective case-note review of coinfected children was carried out in a large UK-based HIV family clinic. Results Of 328 HIV-infected children, 18 were diagnosed and treated for active TB. TB presentation led to HIV diagnosis in eight of these 18 children. TB was confirmed microbiologically in 33% of children. Fifteen of the 18 children presented with pulmonary TB, and three with extrapulmonary TB (EPTB). Immunological status at TB diagnosis did not predict EPTB. The mean CD4 T-cell count at TB presentation was 402 cells/μL (mean CD4 percentage 16%), with a range of 0–790 cells/μL (0–34%). In seven children concurrently treated with HAART and anti-tuberculous therapy (ATT), therapeutic drug monitoring (TDM) guided management. No immune reconstitution disease occurred. There was one death, unrelated to TB, 2 years after completion of ATT. Conclusions An HIV test should be considered in all children diagnosed with TB, especially if there are epidemiological risk factors. Our experience shows that, even with deferral of HAART in concurrently infected children, good therapeutic responses to ATT can be achieved. Where necessary, TDM guiding concurrent HAART and ATT can facilitate good clinical and virological responses.