Information needs of ethnically diverse, vaccine-hesitant parents during decision-making about the HPV vaccine for their adolescent child: a qualitative study.

BACKGROUND: The English schools-based human papillomavirus (HPV) vaccination programme has the potential to eliminate HPV-related cancers if high uptake is achieved. However, unmet information needs among some parents may contribute to persisting lower uptake among minority ethnic groups. Through this study we aimed to understand the information needs of vaccine-hesitant, ethnically diverse parents during decision-making about the HPV vaccine for their adolescent child, to inform the future development of tailored communication materials. METHODS: Recruitment was facilitated thorough healthcare and community organisations within London and the South West of England. Semi-structured interviews took place between April and August 2023. Thematic analysis was undertaken, assisted by NVivo software. RESULTS: Of the 29 parents interviewed, the majority were mothers (79%), belonged to a minority ethnic group (88%), and had an adolescent child unvaccinated against HPV (72%). Five of the interviews were undertaken in the participants' primary language with translation support. Most parents interviewed had limited knowledge about the HPV vaccine and appeared conflicted as to whether vaccines could offer benefits to health. Misunderstanding around the potential of developing serious side-effects (e.g. fertility issues, developing cancer) were factors that could negatively impact decision-making by parents. Stigma associated with the sexual transmissibility of HPV did not always negatively impact decision-making. However, some parents chose not to vaccinate on the basis of perceptions of low risk and a preference to provide education about sexual behaviours to their adolescent child. CONCLUSIONS: Tailoring communication materials to address misunderstandings could support informed decision-making by vaccine hesitant parents for their adolescent children to be vaccinated against HPV. Future communication materials about the HPV vaccine should highlight the benefits of protection against cancer to increase parents' motivation for protect their adolescent child; provide accurate convincing information in relation to the excellent safety profile; and emphasise the importance of providing HPV vaccine at the recommended age, all alongside communicating the universality and commonality of HPV infection. TRIAL REGISTRATION: N/A.

Phenotypic Variability in PRKCD: a Review of the Literature.

PURPOSE: Protein kinase C δ (PKCδ) deficiency is a rare genetic disorder identified as a monogenic cause of systemic lupus erythematosus in 2013. Since the first cases were described, the phenotype has expanded to include children presenting with autoimmune lymphoproliferative syndrome-related syndromes and infection susceptibility similar to chronic granulomatous disease or combined immunodeficiency. We review the current published data regarding the pathophysiology, clinical presentation, investigation and management of PKCδ deficiency. METHODS: Literature review was performed using MEDLINE. RESULTS: Twenty cases have been described in the literature with significant heterogeneity. CONCLUSION: The variation in clinical presentation delineates the broad and critical role of PKCδ in immune tolerance and effector functions against pathogens.

Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in children aged 6-17 years: a preliminary report of COV006, a phase 2 single-blind, randomised, controlled trial.

BACKGROUND: Vaccination of children and young people against SARS-CoV-2 is recommended in some countries. Scarce data have been published on immune responses induced by COVID-19 vaccines in people younger than 18 years compared with the same data that are available in adults. METHODS: COV006 is a phase 2, single-blind, randomised, controlled trial of ChAdOx1 nCoV-19 (AZD1222) in children and adolescents at four trial sites in the UK. Healthy participants aged 6-17 years, who did not have a history of chronic respiratory conditions, laboratory-confirmed COVID-19, or previously received capsular group B meningococcal vaccine (the control), were randomly assigned to four groups (4:1:4:1) to receive two intramuscular doses of 5 × 1010 viral particles of ChAdOx1 nCoV-19 or control, 28 days or 84 days apart. Participants, clinical investigators, and the laboratory team were masked to treatment allocation. Study groups were stratified by age, and participants aged 12-17 years were enrolled before those aged 6-11 years. Due to the restrictions in the use of ChAdOx1 nCoV-19 in people younger than 30 years that were introduced during the study, only participants aged 12-17 years who were randomly assigned to the 28-day interval group had received their vaccinations at the intended interval (day 28). The remaining participants received their second dose at day 112. The primary outcome was assessment of safety and tolerability in the safety population, which included all participants who received at least one dose of the study drug. The secondary outcome was immunogenicity, which was assessed in participants who were seronegative to the nucleocapsid protein at baseline and received both prime and boost vaccine. This study is registered with ISRCTN (15638344). FINDINGS: Between Feb 15 and April 2, 2021, 262 participants (150 [57%] participants aged 12-17 years and 112 [43%] aged 6-11 years; due to the change in the UK vaccination policy, the study terminated recruitment of the younger age group before the planned number of participants had been enrolled) were randomly assigned to receive vaccination with two doses of either ChAdOx1 nCoV-19 (n=211 [n=105 at day 28 and n=106 at day 84]) or control (n=51 [n=26 at day 28 and n=25 at day 84]). One participant in the ChAdOx1 nCoV-19 day 28 group in the younger age bracket withdrew their consent before receiving a first dose. Of the participants who received ChAdOx1 nCoV-19, 169 (80%) of 210 participants reported at least one solicited local or systemic adverse event up to 7 days following the first dose, and 146 (76%) of 193 participants following the second dose. No serious adverse events related to ChAdOx1 nCoV-19 administration were recorded by the data cutoff date on Oct 28, 2021. Of the participants who received at least one dose of ChAdOx1 nCoV-19, there were 128 unsolicited adverse events up to 28 days after vaccination reported by 83 (40%) of 210 participants. One participant aged 6-11 years receiving ChAdOx1 nCoV-19 reported a grade 4 fever of 40·2°C on day 1 following first vaccination, which resolved within 24 h. Pain and tenderness were the most common local solicited adverse events for all the ChAdOx1 nCoV-19 and capsular group B meningococcal groups following both doses. Of the 242 participants with available serostatus data, 14 (6%) were seropositive at baseline. Serostatus data were not available for 20 (8%) of 262 participants. Among seronegative participants who received ChAdOx1 nCoV-19, anti-SARS-CoV-2 IgG and pseudoneutralising antibody titres at day 28 after the second dose were higher in participants aged 12-17 years with a longer interval between doses (geometric means of 73 371 arbitrary units [AU]/mL [95% CI 58 685-91 733] and 299 half-maximal inhibitory concentration [IC50; 95% CI 230-390]) compared with those aged 12-17 years who received their vaccines 28 days apart (43 280 AU/mL [95% CI 35 852-52 246] and 150 IC50 [95% CI 116-194]). Humoral responses were higher in those aged 6-11 years than in those aged 12-17 years receiving their second dose at the same 112-day interval (geometric mean ratios 1·48 [95% CI 1·07-2·07] for anti-SARS-CoV-2 IgG and 2·96 [1·89-4·62] for pseudoneutralising antibody titres). Cellular responses peaked after a first dose of ChAdOx1 nCoV-19 across all age and interval groups and remained above baseline after a second vaccination. INTERPRETATION: ChAdOx1 nCoV-19 is well tolerated and immunogenic in children aged 6-17 years, inducing concentrations of antibody that are similar to those associated with high efficacy in phase 3 studies in adults. No safety concerns were raised in this trial. FUNDING: AstraZeneca and the UK Department of Health and Social Care through the UK National Institute for Health and Care Research.

Increased reports of severe myocarditis associated with enterovirus infection in neonates, United Kingdom, 27 June 2022 to 26 April 2023.

Enteroviruses are a common cause of seasonal childhood infections. The vast majority of enterovirus infections are mild and self-limiting, although neonates can sometimes develop severe disease. Myocarditis is a rare complication of enterovirus infection. Between June 2022 and April 2023, twenty cases of severe neonatal enteroviral myocarditis caused by coxsackie B viruses were reported in the United Kingdom. Sixteen required critical care support and two died. Enterovirus PCR on whole blood was the most sensitive diagnostic test. We describe the initial public health investigation into this cluster and aim to raise awareness among paediatricians, laboratories and public health specialists.

Tailing growth, neonatal jaundice and anaemia.

At medical school, there is a phrase to help us remember that common things are common: 'If you hear hooves think horses, not zebras'. However, zebras do exist, and from time to time in general paediatric and neonatal practice, we will encounter these rare diagnoses, more of which we can now accurately diagnose through the ever-expanding field of genomics. Our case demonstrates how a rare diagnosis can present with common features of growth restriction, jaundice and anaemia. Paediatricians therefore require a high index of suspicion and increasing knowledge of the logistics of genetic testing.

Impact of new consent procedures on uptake of the schools-based human papillomavirus (HPV) vaccination programme.

BACKGROUND: Local policy change initiating new consent procedures was introduced during 2017-2018 for the human papillomavirus (HPV) vaccination programme year in two local authorities in the south-west of England. This study aims to assess impact on uptake and inequalities. METHODS: Publicly available aggregate and individual-level routine data were retrieved for the programme years 2015-2016 to 2018-2019. Statistical analyses were undertaken to show: (i) change in uptake in intervention local authorities in comparison to matched local authorities and (ii) change in uptake overall, and by local authority, school type, ethnicity and deprivation. RESULTS: Aggregate data showed uptake in Local Authority One increased from 76.3% to 82.5% in the post-intervention period (risk difference: 6.2% P = 0.17), with a difference-in-differences effect of 11.5% (P = 0.03). There was no evidence for a difference-in-differences effect in Local Authority Two (P = 0.76). Individual-level data showed overall uptake increased post-intervention (risk difference: +1.1%, P = 0.05), and for young women attending school in Local Authority One (risk difference: 2.3%, P < 0.01). No strong evidence for change by school category, ethnic group and deprivation was found. CONCLUSION: Implementation of new consent procedures can improve and overcome trends for decreasing uptake among matched local authorities. However, no evidence for reduction in inequalities was found. IMPLICATIONS AND DISCUSSION: The new consent procedures increased uptake in one of the intervention sites and appeared to overcome trends for decreasing uptake in matched sites. There are issues in relation to the quality of data which require addressing.

Influence of commissioned provider type and deprivation score on uptake of the childhood flu immunization.

BACKGROUND: Since 2015/16 the UK seasonal influenza immunization programme has included children aged 5 and 6 years. In the South West of England school-based providers, GPs or community pharmacies were commissioned to deliver the vaccine depending on the locality. We aimed to assess variation in vaccine uptake in relation to the type of commissioned provider, and levels of socioeconomic deprivation. METHODS: Data from the South West of England (2015-16 season) were analysed using multilevel logistic regression to assess variation in vaccine uptake by type of commissioned provider, allowing for clustering of children within delivery sites. RESULTS: Overall uptake in 5 and 6 year olds was 34.3% (37 555/109 404). Vaccine uptake was highest when commissioned through school-based programmes 50.2% (9983/19 867) and lowest when commissioned through pharmacies, 23.1% (4269/18 479). Delivery through schools resulted in less variation by site and equal uptake across age groups, in contrast to GP and pharmacy delivery for which uptake was lower among 6 year olds. Vaccine uptake decreased with increasing levels of deprivation across all types of commissioned provider. CONCLUSION: School-based programmes achieve the highest and most consistent rates of childhood influenza vaccination. Interventions are still needed to promote more equitable uptake of the childhood influenza vaccine.

Young women's autonomy and information needs in the schools-based HPV vaccination programme: a qualitative study.

BACKGROUND: Until 2019, the English schools-based human papillomavirus (HPV) vaccination programme was offered to young women (but not young men) aged 12 to 13 years to reduce HPV-related morbidity and mortality. The aim of this study is to explore the extent to which young women were able to exercise autonomy within the HPV vaccination programme. We consider the perspectives of young women, parents and professionals and how this was influenced by the content and form of information provided. METHODS: Recruitment was facilitated through a healthcare organisation, schools and community organisations in a local authority in the south-west of England. Researcher observations of HPV vaccination sessions were carried out in three schools. Semi-structured interviews took place with 53 participants (young women, parents of adolescent children, school staff and immunisation nurses) during the 2017/18 and 2018/19 programme years. Interviews were recorded digitally and transcribed verbatim. Thematic analysis was undertaken, assisted by NVivo software. RESULTS: Young women's active participation and independence within the HPV vaccination programme was constrained by the setting of vaccination and the primacy of parental consent procedures. The authoritarian school structure influenced the degree to which young women were able to actively participate in decisions about the HPV vaccination programme. Young women exercised some power, either to avoid or receive the vaccine, by intercepting parental consent forms and procedures. Reliance on leaflets to communicate information led to unmet information needs for young women and their families. Communication may be improved by healthcare professional advocacy, accessible formats of information, and delivery of educational sessions. CONCLUSIONS: Strategies to improve communication about the HPV vaccine may increase young people's autonomy in consent procedures, clarify young people's rights and responsibilities in relation to their health care services, and result in higher uptake of the HPV vaccination programme. TRIAL REGISTRATION: ISRCTN 49086105 ; Date of registration: 12 January 2018; Prospectively registered.

Chronic recurrent multifocal osteomyelitis in children and adults: current understanding and areas for development.

Since the first descriptions of chronic recurrent multifocal osteomyelitis in the 1970s, there have been numerous case reports in the literature; both unusual case reports and case series from all over the world. Our understanding of the pathogenesis has significantly changed, with it now being regarded as an autoinflammatory condition. Treatment options have also expanded, but little progress has been made in developing the evidence for treatments. Advancing gene studies have provided a mouse model, but the quest for a single gene to match the phenotype has been elusive. Early cohorts of patients have grown up into adults, allowing prospective data to inform the expected outcomes.

Efficacy of pamidronate therapy in children with chronic non-bacterial osteitis: disease activity assessment by whole body magnetic resonance imaging.

OBJECTIVE: The aim of this study was to describe the efficacy of pamidronate therapy on disease activity in children with chronic non-bacterial osteitis (CNO) using whole body MRI (WB-MRI). METHODS: Clinical assessment and WB-MRI were obtained in 11 children before and after 1 year of pamidronate therapy using a 1.5 T MRI scanner and short tau inversion recovery sequences. The images were reported by a paediatric radiologist. RESULTS: WB-MRI identified 75 lesions in 11 patients; 16 of these lesions had not been detected by clinical examination. Follow-up MRI after 1 year of pamidronate showed complete resolution of inflammation in 45 lesions, moderate improvement in 10 lesions and no change in 20 lesions. Two new lesions developed while on treatment. CONCLUSION: WB-MRI allows a more accurate assessment of the disease extent in CNO than clinical examination alone and is useful in the objective measurement of treatment efficacy. Pamidronate appears to be an effective treatment in children with CNO unresponsive to NSAIDs.

Chronic recurrent multifocal osteomyelitis.

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disease occurring primarily in children and adolescents. Episodes of systemic inflammation occur due to immune dysregulation without autoantibodies, pathogens or antigen-specific T cells. CRMO is characterised by the insidious onset of pain with swelling and tenderness over the affected bones. Clavicular involvement was the classical description; however, the metaphyses and epiphyses of long bones are frequently affected. Lesions may occur in any bone, including vertebrae. Characteristic imaging includes bone oedema, lytic areas, periosteal reaction and soft tissue reaction. Biopsies from affected areas display polymorphonuclear leucocytes with osteoclasts and necrosis in the early stages. Subsequently, lymphocytes and plasma cells predominate followed by fibrosis and signs of reactive new bone forming around the inflammation. Diagnosis is facilitated by the use of STIR MRI scanning, potentially obviating the need for biopsy and unnecessary long-term antibiotics due to incorrect diagnosis. Treatment options include non-steroidal anti-inflammatory drugs and bisphosphonates. Biologics have been tried in resistant cases with promising initial results. Gene identification has not proved easy although research in this area continues. Early descriptions of the disease suggested a benign course; however, longer-term follow up shows that it can cause significant morbidity and longer-term disability. Although it has always been thought of as very rare, the prevalence is likely to be vastly underestimated due to poor recognition of the disease.

HLA-B*27 is associated with CNO in a European cohort.

OBJECTIVES: To determine the influence of HLA-B27 positivity on risk of developing chronic nonbacterial osteomyelitis (CNO). METHODS: HLA-B*27 genotype was assessed in 3 European CNO populations and compared with local control populations (572 cases, 33,256 controls). Regional or whole-body MRI was performed at diagnosis and follow-up in all cases which reduces the risk of disease misclassification. Genotyping was performed using either next generation DNA sequencing or PCR based molecular typing. Statistical analysis used Fisher's exact test with Bonferroni correction and a fixed effects model for meta-analysis of odds ratios. RESULTS: HLA-B*27 frequency was higher in all 3 populations compared with local controls (combined odds ratio (OR) = 2.2, p-value = 3 × 10-11). This association was much stronger in male compared with female cases (OR = 1.99, corrected p-value = 0.015). However, the HLA-B*27 status was not statistically significantly associated with co-occurrence of psoriasis, arthritis or inflammatory bowel disease. CONCLUSION: Carriage of HLA-B*27 is associated with greater risk of developing CNO, particularly in male cases.

Epidemiology of hospitalisations due to chickenpox and quality of life lost in community and hospital settings: protocol for a prospective cohort study across two countries.

INTRODUCTION: While still a ubiquitous disease of childhood, chickenpox has been effectively controlled in many countries through the use of vaccination. Previous health economic assessment of the use of these vaccines in the UK were based on limited quality of life data and only routinely collected epidemiological outcomes. METHODS AND ANALYSIS: This two armed study will carry prospective surveillance of hospital admissions and recruit from community settings to measure the acute quality of life loss caused by paediatric chickenpox both in the UK and in Portugal. The quality of life effects on children and their primary and secondary caregivers will be assessed using the EuroQol EQ-5D with the Child Health Utility instrument (CHU-9) in addition for children. Results will be used to derive quality-adjusted life year loss estimates for cases of simple varicella and the secondary complications. ETHICS AND DISSEMINATION: We have received National Health Service ethical approval (REC ref: 18/ES/0040) for the inpatient arm, university ethical approval (University of Bristol ref: 60721) for the community arm and 10 sites currently are recruiting in the UK and 14 in Portugal. Informed consent is obtained from the parent(s). Results will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ISRCTN15017985.

Lateral flow test performance in children for SARS-CoV-2 using anterior nasal and buccal swabbing: sensitivity, specificity, negative and positive predictive values.

OBJECTIVE: To determine if the sensitivity of the lateral flow test is dependent on the viral load and on the location of swabbing in the respiratory tract in children. DESIGN: Phase 1: Routinely performed reverse transcriptase PCR (RT-PCR) using nose and throat (NT) swabs or endotracheal (ET) aspirates were compared with Innova lateral flow tests (LFTs) using anterior nasal (AN) swabs. Phase 2: RT-PCR-positive children underwent paired AN RT-PCR and LFT and/or paired AN RT-PCR and buccal LFT. SETTING: Tertiary paediatric hospitals. PATIENTS: Children under the age of 18 years. Phase 1: undergoing routine testing, phase 2: known SARS-CoV-2 positive. RESULTS: Phase 1: 435 paired swabs taken in 431 asymptomatic patients resulted in 8 positive RT-PCRs, 9 PCR test failures and 418 negative RT-PCRs from NT or ET swabs. The test performance of AN LFT demonstrated sensitivity: 25% (4%-59%), specificity: 100% (99%-100%), positive predictive value (PPV): 100% (18%-100%) and negative predictive value (NPV): 99% (97%-99%).Phase 2: 14 AN RT-PCR-positive results demonstrated a sensitivity of 77% (50%-92%) of LFTs performed on AN swabs. 15/16 paired buccal LFT swabs were negative. CONCLUSION: The NPV, PPV and specificity of LFTs are excellent. The sensitivity of LFTs compared with RT-PCR is good when the samples are colocated but may be reduced when the LFT swab is taken from the AN. Buccal swabs are not appropriate for LFT testing. Careful consideration of the swabbing reason, the tolerance of the child and the requirements for test processing (eg, rapidity of results) should be undertaken within hospital settings. TRIAL REGISTRATION NUMBER: NCT04629157.

Serum HCoV-spike specific antibodies do not protect against subsequent SARS-CoV-2 infection in children and adolescents.

SARS-CoV-2 infections in children are generally asymptomatic or mild and rarely progress to severe disease and hospitalization. Why this is so remains unclear. Here we explore the potential for protection due to pre-existing cross-reactive seasonal coronavirus antibodies and compare the rate of antibody decline for nucleocapsid and spike protein in serum and oral fluid against SARS-CoV-2 within the pediatric population. No differences in seasonal coronaviruses antibody concentrations were found at baseline between cases and controls, suggesting no protective effect from pre-existing immunity against seasonal coronaviruses. Antibodies against seasonal betacoronaviruses were boosted in response to SARS-CoV-2 infection. In serum, anti-nucleocapsid antibodies fell below the threshold of positivity more quickly than anti-spike protein antibodies. These findings add to our understanding of protection against infection with SARS-CoV-2 within the pediatric population, which is important when considering pediatric SARS-CoV-2 immunization policies.

Management of Enteritis Associated With Tricohepatoenteric Syndrome due to SKIV2L Mutation Using the Combination of JAK1/2 Inhibition and Azathioprine.

Tricohepatoenteric syndrome is a rare genetic disorder caused by mutations in SKIV2L or TTC37. An upregulation of type 1 interferon signaling is associated with the SKIV2L variation. Introduction of Baricitinib as a JAK1/ 2 kinase inhibitor alongside traditional immunosuppressive agents successfully reduced the symptoms of enteritis by blocking the inflammogenic effects of type 1 interferonopathy in a case of tricohepatoenteric syndrome diagnosed in a 5-year-old boy.