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ObjectiveTo evaluate neuromotor repertoires and developmental milestones in infants exposed to antenatal COVID-19.DesignLongitudinal cohort study.SettingHospital-based study in Los Angeles, USA and Rio de Janeiro, Brazil between March 2020 and December 2021.ParticipantsInfants born to mothers with COVID-19 during pregnancy and prepandemic control infants from the Graz University Database.InterventionsGeneral movement assessment (GMA) videos between 3 and 5 months post-term age were collected and clinical assessments/developmental milestones evaluated at 6-8 months of age. Cases were matched by gestational age, gender and post-term age to prepandemic neurotypical unexposed controls from the database.Main outcome measuresMotor Optimality Scores Revised (MOS-R) at 3-5 months. Presence of developmental delay (DD) at 6-8 months.Results239 infants were enrolled; 124 cases (83 in the USA/41 in Brazil) and 115 controls. GMA was assessed in 115 cases and 115 controls; 25% were preterm. Median MOS-R in cases was 23 (IQR 21-24, range 9-28) vs 25 (IQR 24-26, range 20-28) in controls, p

ObjectivesWe aimed to evaluate the international variation in the use of evidence-based management (EBM) in bronchiolitis. We hypothesised that management consistent with full-EBM practices is associated with the research network of care, adjusted for patient-level characteristics. Secondary objectives were to determine the association between full-EBM and (1) hospitalisation and (2) emergency department (ED) revisits resulting in hospitalisation within 21 days.DesignA secondary analysis of a retrospective cohort study.Setting38 paediatric EDs belonging to the Paediatric Emergency Research Network in Canada, USA, Australia/New Zealand UK/Ireland and Spain/Portugal.PatientsOtherwise healthy infants 2-11 months old diagnosed with bronchiolitis between 1 January 2013 and 31 December, 2013.Outcome measuresPrimary outcome was management consistent with full-EBM, that is, no bronchodilators/corticosteroids/antibiotics, no chest radiography or laboratory testing. Secondary outcomes included hospitalisations during the index and subsequent ED visits.Results1137/2356 (48.3%) infants received full-EBM (ranging from 13.2% in Spain/Portugal to 72.3% in UK/Ireland). Compared with the UK/Ireland, the adjusted ORs (aOR) of full-EBM receipt were lower in Spain/Portugal (aOR 0.08, 95% CI 0.02 to 0.29), Canada (aOR 0.13 (95% CI 0.06 to 0.31) and USA (aOR 0.16 (95% CI 0.07 to 0.35). EBM was less likely in infants with dehydration (aOR 0.49 (95% CI 0.33 to 0.71)), chest retractions (aOR 0.69 (95% CI 0.52 to 0.91)) and nasal flaring (aOR 0.69 (95% CI 0.52 to 0.92)). EBM was associated with reduced odds of hospitalisation at the index visit (aOR 0.77 (95% CI 0.60 to 0.98)) but not at revisits (aOR 1.17 (95% CI 0.74 to 1.85)).ConclusionsInfants with bronchiolitis frequently do not receive full-EBM ED management, particularly those outside of the UK/Ireland. Furthermore, there is marked variation in full-EBM between paediatric emergency networks, and full-EBM delivery is associated with lower likelihood of hospitalisation. Given the global bronchiolitis burden, international ED-focused deimplementation of non-indicated interventions to enhance EBM is needed.

ObjectivePersistent exposure to faecal pathogens due to open defecation may cause environmental enteropathy that, in turn, may lead to undernutrition and vaccine failure in under 5-year-old (u5) children. The Swachh Bharat Mission (SBM) programme in India, launched in 2014, aimed to construct toilets for every household nationwide and reduce open defecation. This programme, if successful, had the potential to reduce the burden of four vaccine preventable diseases (VPDs): diphtheria, pertussis, tetanus and measles. We examine whether increased household toilet availability in Indian districts following SBM corresponds with a reduction in diphtheria, pertussis, tetanus and measles in u5 children.DesignObservational, ecological study.Setting532 districts in 28 Indian states, from 2013 to 2016.Primary outcome and exposureWe retrieved data on district-level change in the annual incidence (per 1000 u5 children) of four VPDs, from 2013 (pre-SBM) to 2016 (post-SBM). We obtained data on our exposure, the change in the percentage of households with toilets (per district), from three large national surveys conducted in 2013 and 2016. We used linear regression analysis, which controlled for change over time in socioeconomic factors, health system-related covariates and pre-SBM annual incidence of VPDs.ResultsA one percentage point increase in households with toilets corresponds with 0.33 fewer measle cases per 1000 u5 children in a district (coefficient: -0.33, 95% CI -0.0641 to -0.014; p

ObjectiveTo quantify the frequency of antibiotic treatments attributable to specific enteric pathogens due to the treatment of diarrhoea among children in the first 2 years of life in low-resource settings.DesignSecondary analysis of a longitudinal birth cohort study, Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED).SettingThis study was conducted at eight sites in Bangladesh, Brazil, India, Nepal, Peru, Pakistan, South Africa and Tanzania.ParticipantsWe analysed 9392 reported diarrhoea episodes, including 6677 with molecular diagnostic test results, as well as 31 408 non-diarrhoeal stools from 1715 children aged 0-2 years with 2 years of complete follow-up data.Primary and secondary outcome measuresWe estimated incidence rates and the proportions of antibiotic use for diarrhoea and for all indications attributable to the top 10 aetiologies of diarrhoea. We estimated associations between specific aetiologies and antibiotic treatment, and assessed whether clinical characteristics of the diarrhoea episodes mediated these relationships.ResultsShigella and rotavirus were the leading causes of antibiotic treatment, responsible for 11.7% and 8.6% of diarrhoea treatments and 14.8 and 10.9 courses per 100 child-years, respectively. Shigella and rotavirus-attributable diarrhoea episodes were 46% (RR: 1.46; 95% CI: 1.33 to 1.60), and 19% (RR: 1.19; 95% CI: 1.09 to 1.31) more likely to be treated with antibiotics, respectively, compared with other aetiologies. Considering antibiotic uses for all indications, these two pathogens accounted for 5.6% of all antibiotic courses, 19.3% of all fluoroquinolone courses and 9.5% of all macrolide courses. Among indicated treatments for dysentery, Shigella and Campylobacter jenjui/Campylobacter coli were responsible for 27.5% and 8.5% of treated episodes, respectively.ConclusionsThe evidence that Shigella and rotavirus were disproportionately responsible for antibiotic use due to their high burden and severity further strengthens the value of interventions targeted to these pathogens. Interventions against Campylobacter could further prevent a large burden of indicated antibiotic treatment for dysentery, which could not be averted by antibiotic stewardship interventions.

ObjectivesTo combat misinformation, engender trust and increase health literacy, we developed a culturally and linguistically appropriate virtual reality (VR) vaccination education platform using community-engaged approaches within a Somali refugee community.DesignCommunity-based participatory research (CBPR) methods including focus group discussions, interviews, and surveys were conducted with Somali community members and expert advisors to design the educational content. Co-design approaches with community input were employed in a phased approach to develop the VR storyline.Participants60 adult Somali refugees and seven expert advisors who specialise in healthcare, autism research, technology development and community engagement.SettingSomali refugees participated at the offices of a community-based organisation, Somali Family Service, in San Diego, California and online. Expert advisors responded to surveys virtually.ResultsWe find that a CBPR approach can be effectively used for the co-design of a VR educational programme. Additionally, cultural and linguistic sensitivities can be incorporated within a VR educational programme and are essential factors for effective community engagement. Finally, effective VR utilisation requires flexibility so that it can be used among community members with varying levels of health and technology literacy.ConclusionWe describe using community co-design to create a culturally and linguistically sensitive VR experience promoting vaccination within a refugee community. Our approach to VR development incorporated community members at each step of the process. Our methodology is potentially applicable to other populations where cultural sensitivities and language are common health education barriers.

ObjectiveTo investigate maternal immunoglobulins' (IgM, IgG) response to SARS-CoV-2 infection during pregnancy and IgG transplacental transfer, to characterise neonatal antibody response to SARS-CoV-2 infection, and to longitudinally follow actively and passively acquired antibodies in infants.DesignA prospective observational study.SettingPublic healthcare system in Santa Clara County (California, USA).ParticipantsWomen with symptomatic or asymptomatic SARS-CoV-2 infection during pregnancy and their infants were enrolled between 15 April 2020 and 31 March 2021.OutcomesSARS-CoV-2 serology analyses in the cord and maternal blood at delivery and longitudinally in infant blood between birth and 28 weeks of life.ResultsOf 145 mothers who tested positive for SARS-CoV-2 during pregnancy, 86 had symptomatic infections: 78 with mild-moderate symptoms, and 8 with severe-critical symptoms. The seropositivity rates of the mothers at delivery was 65% (95% CI 0.56% to 0.73%) and the cord blood was 58% (95% CI 0.49% to 0.66%). IgG levels significantly correlated between the maternal and cord blood (Rs=0.93, p

IntroductionRelatively limited data are available regarding paediatric COVID-19. Although most children appear to have mild or asymptomatic infections, infants and those with comorbidities are at increased risk of experiencing more severe illness and requiring hospitalisation due to COVID-19. The recent but uncommon association of SARS-CoV-2 infection with development of a multisystem inflammatory syndrome has heightened the importance of understanding paediatric SARS-CoV-2 infection.Methods and analysisThe Paediatric Emergency Research Network-COVID-19 cohort study is a rapid, global, prospective cohort study enrolling 12 500 children who are tested for acute SARS-CoV-2 infection. 47 emergency departments across 12 countries on four continents will participate. At enrolment, regardless of SARS-CoV-2 test results, all children will have the same information collected, including clinical, epidemiological, laboratory, imaging and outcome data. Interventions and outcome data will be collected for hospitalised children. For all children, follow-up at 14 and 90 days will collect information on further medical care received, and long-term sequelae, respectively. Statistical models will be designed to identify risk factors for infection and severe outcomes.Ethics and disseminationSites will seek ethical approval locally, and informed consent will be obtained. There is no direct risk or benefit of study participation. Weekly interim analysis will allow for real-time data sharing with regional, national, and international policy makers. Harmonisation and sharing of investigation materials with WHO, will contribute to synergising global efforts for the clinical characterisation of paediatric COVID-19. Our findings will enable the implementation of countermeasures to reduce viral transmission and severe COVID-19 outcomes in children.Trial registration numberNCT04330261.

IntroductionPneumonia is a frequent and costly cause of emergency department (ED) visits and hospitalisations in children. There are no evidence-based, validated tools to assist physicians in management and disposition decisions for children presenting to the ED with community-acquired pneumonia (CAP). The objective of this study is to develop a clinical prediction model to accurately stratify children with CAP who are at risk for low, moderate and severe disease across a global network of EDs.Methods and analysisThis study is a prospective cohort study enrolling up to 4700 children with CAP at EDs at ~80 member sites of the Pediatric Emergency Research Networks (PERN; https://pern-global.com/). We will include children aged 3 months to

Objective: To illustrate an evidence-, theory- and person-based approach to codesign the COMMUNICATE films that support parental decision-making about the human papillomavirus (HPV) vaccine for their teenagers., Design: Codesign study., Setting: Localities covered by two immunisation teams in London and the south-west of England., Methods: The intervention planning phase involved combining evidence from a literature review with qualitative interview data to identify barriers and facilitators to HPV vaccine uptake, as well as design features that should be incorporated within the COMMUNICATE films. The intervention development phase involved identifying guiding principles for the COMMUNICATE films, mapping behaviour change techniques onto the behaviour change wheel and codesigning the COMMUNICATE films. Feedback from users informed modifications to maximise acceptability and feasibility and to support behaviour change., Results: The primary and secondary evidence highlighted important content to include within the COMMUNICATE films: emphasise the benefits of the HPV vaccine, provide transparent information about the safety profile and side effects and emphasise the universality and commonality of HPV infection. A series of scripts were used to guide 4 film shoots to create the content in multiple community languages with 16 participants, including vaccine-hesitant, ethnically diverse parents and professionals. Overall, participants were positive about the films. Potential messengers and ways the films could be distributed, identified by parents, include local social media networks or text messages from general practices. The need for information about the HPV vaccine to be shared by schools ahead of consent being sought was also raised., Conclusions: By using an integrated approach to intervention development, this study has begun to address the need for an intervention to support vaccine-hesitant, ethnically diverse parents' decision-making about the HPV vaccination programme. A future study to codesign, implement and evaluate a communication strategy for the COMMUNICATE films is planned., Competing Interests: Competing interests: AF is a member of the Joint Committee on Vaccination and Immunization and was, until December 2022, chair of the WHO European Technical Advisory Group of Experts on Immunization committee. The other authors have no relevant conflicts of interest to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objective: Low birth weight (LBW) is an important indicator of newborn health and can have long-term implications for a child's development. Spatial exploratory analysis provides a toolkit to gain insight into inequalities in LBW. Few studies in Ghana have explored the spatial distribution of LBW to understand the extent of the problem geographically. This study explores individual and cluster-level distributions of LBW using spatial exploration components for common determinants from nationally representative survey data., Design: We used data from the 2017 Ghana Maternal Health Survey and conducted individual-level and cluster-level analyses of LBW with place and zone of residence in both bivariate and multivariate analyses. By incorporating spatial and survey designs methodology, logistic and Poisson regression models were used to model LBW., Setting: Ghana., Participants: A total of 4127 women aged between 15 and 49 years were included in the individual-level analysis and 864 clusters corresponding to birth weight., Primary and Secondary Outcome Measures: Individual and cluster-level distribution for LBW using spatial components for common determinants., Results: In the individual-level analysis, place and zone of residence were significantly associated with LBW in the bivariate model but not in a multivariate model. Hotspot analysis indicated the presence of LBW clusters in the middle and northern zones of Ghana. Compared with rural areas, clusters in urban areas had significantly lower LBW (p=0.017). Clusters in the northern zone were significantly associated with higher LBW (p=0.018) compared with the coastal zones., Conclusion: Our findings from choropleth hotspot maps suggest LBW clusters in Ghana's northern and middle zones. Disparities between the rural and urban continuum require specific attention to bridge the healthcare system gap for Ghana's northern and middle zones., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Most children with uncomplicated urinary tract infections (UTI) can be managed with oral antibiotics. However, identifying those likely to fail oral and need intravenous antibiotics due to complicating features at presentation is challenging. We aimed to derive, validate and test a score to guide initial antibiotic route., Design: This cohort study enrolled children both prospectively and retrospectively. Patients were divided into two groups based on whether they received intravenous or oral antibiotics after 24 hours, including those who switched between routes. Children diagnosed with confirmed UTI were used to derive then validate the score, comparing complicating clinical features between the two groups. Combinations of significantly differentiating features generated receiver operating characteristic curves and the optimal cut-off for intravenous antibiotic use was selected., Setting: The emergency department of a tertiary paediatric hospital., Participants: All children aged 3 months-17 years with suspected UTI were eligible, and were included if they fulfilled the diagnostic criteria for UTI., Outcome Measures: The effectiveness of the derived clinical score to differentiate patients at presentation who had complicated UTI requiring ongoing intravenous antibiotics., Results: There were 1240 patients, of whom 167 children aged 12 months-11 years with confirmed UTI comprised the derivation cohort. The combination of features that performed optimally (area under curve 0.85, 95% CI 0.79 to 0.91) were: rigors, urological abnormality, fever (≥38°C), emesis, recurrent (≥3) UTI, tachycardia: the RUPERT score (1 point each, maximum 6). A score ≥3 accurately classified route of antibiotics after 24 hours for 80% patients (sensitivity 77%, specificity 81%). For the 168 patients in the validation cohort, the score accurately classified 76% (sensitivity 67%, specificity 78%). The score tested well in 'probable' UTI and adolescents, and less well in infants., Conclusion: The Melbourne RUPERT score provides the first standardised, easy-to-use score to aid clinicians in deciding route of antibiotics for more complicated UTI in children. It now needs prospective validation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objectives: This study compared the infant vaccination trends a year before and a year after the onset of the COVID-19 pandemic in selected urban and rural communities in Ibadan, Nigeria., Design: This was a cross-sectional study in which data were extracted from infant vaccination records., Setting: Two rural and three urban vaccination centres in primary health clinics at Ibadan Southeast and Olúyòlé local government areas, respectively., Participants: Infant vaccination records 1 year before and 1 year after the onset of the COVID-19 pandemic (March 2019-February 2020 and March 2020-February 2021, respectively)., Outcome Measures: Timeliness of vaccination (vaccination taken within 2 weeks of appointment) and vaccination completion according to the Nigerian routine infant vaccination schedule., Results: 2000 vaccination records were included in the study (1013 (50.6%) for male infants). 840 (42.0%) of the records were from the rural immunisation clinics. There were 1194 (59.7%) and 806 (40.3%) records from before and after the onset of the COVID-19 pandemic, respectively. Before the pandemic, birth dose vaccines were timelier among infants from urban communities, while vaccines given at 6 weeks were timelier in the rural areas. Following the onset of the pandemic, the rural communities had a higher proportion of infants with timelier and complete vaccination except for the birth dose vaccines. Overall, there was higher vaccination completion before the pandemic, and this was higher in the rural compared with the urban communities both before (54.8% vs 11.7%) and after (23.6% vs 1.0%) the onset of the pandemic., Conclusions: A decline in infant vaccination uptake, timeliness and completion persisted 1 year after the COVID-19 pandemic onset, and urban communities were more affected. More efforts are required to ensure optimal infant vaccination, especially in urban communities, to forestall outbreaks of vaccine-preventable diseases., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: National-level coverage estimates of maternal and child health (MCH) services mask district-level and community-level geographical inequities. The purpose of this study is to estimate grid-level coverage of essential MCH services in Nigeria using machine learning techniques., Methods: Essential MCH services in this study included antenatal care, facility-based delivery, childhood vaccinations and treatments of childhood illnesses. We estimated generalised additive models (GAMs) and gradient boosting regressions (GB) for each essential MCH service using data from five national representative cross-sectional surveys in Nigeria from 2003 to 2018 and geospatial socioeconomic, environmental and physical characteristics. Using the best-performed model for each service, we map predicted coverage at 1 km 2 and 5 km 2 spatial resolutions in urban and rural areas, respectively., Results: GAMs consistently outperformed GB models across a range of essential MCH services, demonstrating low systematic prediction errors. High-resolution maps revealed stark geographic disparities in MCH service coverage, especially between rural and urban areas and among different states and service types. Temporal trends indicated an overall increase in MCH service coverage from 2003 to 2018, although with variations by service type and location. Priority areas with lower coverage of both maternal and vaccination services were identified, mostly located in the northern parts of Nigeria., Conclusion: High-resolution spatial estimates can guide geographic prioritisation and help develop better strategies for implementation plans, allowing limited resources to be targeted to areas with lower coverage of essential MCH services., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Globally, the number of children/adolescents exposed to HIV but uninfected (HIV-exposed uninfected, HEU) is growing. The HEU outcomes: population-evaluation and screening strategies study was designed to provide population-level evidence of the impact of HIV and recent antiretroviral therapy regimen exposure on neurodevelopmental, hearing and mental health outcomes from infancy to adolescence., Participants: The study includes a prospective mother-infant cohort and cross-sectional child/youth-caregiver cohorts conducted in Kenya.Between 2021 and 2022, the study enrolled 2000 mother-infant pairs (1000 HEU and 1000 HIV-unexposed uninfected (HUU)) for longitudinal follow-up. Infants were eligible if they were aged 4-10 weeks and healthy. Mothers were eligible if their HIV status was known and were ≥18 years. Study visits are 6 monthly until the child reaches age 3 years.Cross-sectional cohorts spanning ages 3-18 years started enrolment in 2022. Target enrolment is 4400 children/youth (4000 HEU and 400 HUU). Children and youth are eligible if they are HIV negative, maternal HIV status and timing of diagnosis is known, and caregivers are ≥18 years.Data on infant/child/youth growth, neurodevelopment, mental health, morbidity and hearing are collected at enrolment using standardised tools. Dry blood spots samples are collected for telomere length assessment at baseline and yearly for the longitudinal cohort. Growth z-scores, neurodevelopmental scores, telomere length and prevalence of developmental and hearing problems will be compared between HEU/HUU populations., Findings to Date: Full cohort enrolment for the longitudinal cohort is complete and participants are in follow-up. At 1 year of age, comparing HEU to HUU neurodevelopment using the Malawi developmental assessment tool, we found that HEU infants had higher language scores and comparable scores in fine motor, gross motor and social scores. The cross-sectional cohort has enrolled over 2000 participants and recruitment is ongoing., Future Plans: Longitudinal cohort follow-up and enrolment to the cross-sectional study will be completed in June 2024., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Family caregivers of children living with HIV/AIDS in most cases are found to be overwhelmed and under-resourced, yet they are believed to be the primary source of support for children living with HIV/AIDS. Family caregivers experience different challenges that affect their children's antiretroviral therapy (ART) adherence., Aim: This study explored the lived experiences of family caregivers of children living with HIV/AIDS who sought ART services for these children at the St Joseph's Hospital of Jirapa, Ghana., Method: Using a qualitative phenomenology design and a semistructured in-depth interview guide and using purposive sampling, data were gathered from 13 family caregivers of children living with HIV/AIDS receiving ART treatment at St Joseph's Hospital, Jirapa following ethical approval. All interviews were audio-taped and transcribed verbatim. Reflexive thematic analysis was used to analyse the transcribed data., Findings: Six themes were generated: five challenges and one support. Family caregivers of children living with HIV/AIDS experienced: (1) Financial challenges, (2) Human-related challenges, (3) Challenges at HIV testing and counselling (HTC) centres, (4) Challenges with transportation, (5) Challenges in disclosing children's HIV status to them and (6) Support received from HTC and their family members., Conclusion and Recommendation: Family caregivers of children living with HIV/AIDS experience daunting challenges in their quest to care for their children. Governmental and non-governmental HIV/AIDS programme support should include small business skills training and acquisition including capital to help set up small-scale businesses for such caregivers to reduce their financial challenges. Access to ART at clinics closer to caregivers is also key to promoting adherence. Family and community support has been recognised as key to enhancing ART adherence. Education of caregivers on policy regarding disclosure of the HIV/AIDS status of children, the need to work to reduce the time spent by caregivers at HTC, and ensuring privacy by limiting access to HTCs to only caregivers and their children, are important to enhancing adherence., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: HIV is a major public health issue affecting millions globally. Women and girls account for 46% of new HIV infections in 2022 and approximately 1.3 million females become pregnant every year. Vertical transmission of HIV from persons living with HIV (PLHIV) to infants may occur through different modalities, such as through breast/chest feeding. Notably, 82% of PLHIV who chose to breast/chest feed are on antiretroviral therapy (ART) when feeding their infants. Precise estimates of the risk of postpartum transmission to infants during breast/chest feeding at varying viral load levels remain a significant gap in the literature., Methods and Analysis: A rapid systematic search of electronic databases will be conducted from January 2005 to the present, including Medline, Embase and Global Health. The objective of this rapid review is to explore and assess the available evidence on the effect of varying viral load levels on the risk of HIV transmission to infants during breast/chest feeding when the birthing or gestational parent living with HIV is on ART. Study characteristics will be summarised and reported to support the narrative summary of the findings. The focus will be on the absolute risk of HIV transmission from birthing parent to infant during chest/breast feeding. The findings will also be stratified by month, including the risk of HIV transmission for 6 months and greater than 6 months postpartum. We will ascertain the risk of bias using A Measurement Tool to Assess Systematic Reviews 2, Quality of Prognosis Studies and Downs and Black checklist for the appropriate study type. A summary score will not be calculated, rather the strengths and limitations of the studies will be narratively described., Ethics and Dissemination: No human subjects will be involved in the research. The findings of this rapid review will inform a future systematic review and will be disseminated through peer-reviewed publications, presentations and conferences., Prospero Registration Number: CRD42024499393., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: In trials of acute severe infections or inflammations frequent administration of non-randomised treatment (ie, intercurrent event) in response to clinical events is expected. These events may affect the interpretation of trial findings. Swissped-RECOVERY was set up as one of the first randomised controlled trials worldwide, investigating the comparative effectiveness of anti-inflammatory treatment with intravenous methylprednisolone or intravenous immunoglobulins in children and adolescents with Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS). We present one approach towards improving the interpretation of non-randomised treatment in a randomised controlled trial., Design: This is a pre-planned ancillary analysis of the Swissped-RECOVERY trial, a randomised multicentre open-label two-arm trial., Setting: 10 Swiss paediatric hospitals (secondary and tertiary care) participated., Participants: Paediatric patients hospitalised with PIMS-TS., Interventions: All patient-first intercurrent events, if applicable, were presented to an independent adjudication committee consisting of four international paediatric COVID-19 experts to provide independent clinical adjudication to a set of standardised questions relating to whether additional non-randomised treatments were clinically indicated and disease classification at the time of the intercurrent event., Results: Of 41 treatments in 75 participants (24/41 (59%) and 17/41 (41%) in the intravenous methylprednisolone and immunoglobulin arms of the trial, respectively), two-thirds were considered indicated. The most common treatment (oral glucocorticoids, 14/41, 35%) was mostly considered not indicated (11/14, 79%), although in line with local guidelines. Intercurrent events among patients with Shock-like PIMS-TS at baseline were mostly considered indicated. A significant proportion of patients with undifferentiated PIMS-TS at baseline were not attributed to the same group at the time of the intercurrent event (6/12 unchanged, 4/12 Kawasaki disease-like, 2/12 Shock-like)., Conclusion: The masked adjudication of intercurrent events contributes to the interpretation of results in open-label trials and should be incorporated in the future., Trial Registration Numbers: SNCTP000004720 and NCT04826588., Competing Interests: Competing interests: JAB received grant support paid to the institution from the European and Developing Countries Clinical Trials Partnership (PediCaP, RIA2017MC-2023), Horizon 2020 (NeoIPC, grant 965328), the Swiss National Science Foundation (KIDS-STEP, grant 173532), National Institute for Health Research (CAP-IT, project 13/88/11), Innosuisse (SPEARHEAD flagship grant), the Swiss Personalised Health Network (Secretariat for Education Research and Innovation) (SwissPedHealth, award NDS-2021-911), in the past 36 months; consulting fees paid to the institution from Shionogi, Sandoz, Basilea, and GSK; payments to the institution for presentations, lectures, speakers bureaus, manuscript writing or educational events in the past 36 months from Pfizer, Sandoz and Bayer; participated at independent data monitoring committee boards of Avenir trial (member, expenses), Lakana trial (member, unfunded), CURLY trial (Chair, unfunded) in the past 36 months; is the vice president of the SwissPedNet (unpaid) and leadership of Severe Bacterial Infection and Antimicrobial Resistance working group of the Penta Foundation (unpaid). TW gave presentations for Novartis (payment to the institution) in the past 36 months. AB had received fixed-term consultancy fees from Gilead. KW is supported by the Crick African Network (CAN). The CAN receives its funding from the UK’s Global Challenges Research Fund (MR/P028071/1), the Francis Crick Institute which receives its core funding from Cancer Research UK (FC1001647), the UK Medical Research Council (FC1001647) and the Wellcome Trust (FC1001647). KW is also supported by the South African Medical Research Council with funds received from the National Treasury. PR received grant support from ViiV and consulting fees from MSD. AT received grant support paid to the institution/UCSD from the National Institute of Health and consulted Janssen Pharmaceuticals and Kiniksa with no payment received. All other authors declared no conflicts of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: This study aimed to assess the coutilisation of oral rehydration solution (ORS) and zinc for treating diarrhoea and its associated factors among under-5 children in East Africa., Design: Cross-sectional study design. Multilevel Poisson regression analysis with robust variance was fitted to identify predictors of zinc and ORS coutilisation. An adjusted prevalence ratio (aPR) with a 95% CI was reported to declare the statistical significance., Setting: Twelve East African countries., Participants: 16 850 under-5 children who had diarrhoea were included in the study., Result: In East African nations, the coutilisation of ORS and zinc for the treatment of diarrhoea in children under 5 was 53.27% with a 95% CI (52.54% to 54.01%). Children of mothers with primary education (aPR 1.15, 95% CI 1.09 to 1.20), secondary education (aPR 1.08, 95% CI 1.02 to 1.14), higer education (aPR 1.19, 95% CI 1.10 to 1.29), those from maternal age category of 20-24 (aPR 1.14, 95% CI 1.07 to 1.21), age category of 25-29 (aPR 1.13, 95% CI 1.06 to 1.21), age category of 30-34 (aPR 1.09, 95% CI 1.02 to 1.16), those from wealthy households (aPR 1.04, 95% CI 1.01 to 1.09) and those who have a media exposure (aPR 1.04, 95% CI 1.01 to 1.08) were more likely to receive combination., Conclusion: Only half of the under-5 children with diarrhoea in East Africa were treated with a combination of ORS and zinc. To increase the use of the suggested combination therapy of ORS with zinc, it is important to empower women through education and prevent teen pregnancy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objective: An umbrella review providing a comprehensive synthesis of the interventions that are effective in providing routine immunisation outcomes for children in low and middle-income countries (L&MICs)., Design: A systematic review of systematic reviews, or an umbrella review., Data Sources: We comprehensively searched 11 academic databases and 23 grey literature sources. The search was adopted from an evidence gap map on routine child immunisation sector in L&MICs, which was done on 5 May 2020. We updated the search in October 2021., Eligibility Criteria: We included systematic reviews assessing the effectiveness of any intervention on routine childhood immunisation outcomes in L&MICs., Data Extraction and Synthesis: Search results were screened by two reviewers independently applying predefined inclusion and exclusion criteria. Data were extracted by two researchers independently. The Specialist Unit for Review Evidence checklist was used to assess review quality. A mixed-methods synthesis was employed focusing on meta-analytical and narrative elements to accommodate both the quantitative and qualitative information available from the included reviews., Results: 62 systematic reviews are included in this umbrella review. We find caregiver-oriented interventions have large positive and statistically significant effects, especially those focusing on short-term sensitisation and education campaigns as well as written messages to caregivers. For health system-oriented interventions the evidence base is thin and derived from narrative synthesis suggesting positive effects for home visits, mixed effects for pay-for-performance schemes and inconclusive effects for contracting out services to non-governmental providers. For all other interventions under this category, the evidence is either limited or not available. For community-oriented interventions, a recent high-quality mixed-methods review suggests positive but small effects. Overall, the evidence base is highly heterogenous in terms of scope, intervention types and outcomes., Conclusion: Interventions oriented towards caregivers and communities are effective in improving routine child immunisation outcomes. The evidence base on health system-oriented interventions is scant not allowing us to reach firm conclusions, except for home visits. Large evidence gaps exist and need to be addressed. For example, more high-quality evidence is needed for specific caregiver-oriented interventions (eg, monetary incentives) as well as health system-oriented (eg, health workers and data systems) and community-oriented interventions. We also need to better understand complementarity of different intervention types., Competing Interests: Competing interests: As members of 3ie staff, MJ had been involved in reviewing deliverables for the evaluations funded by 3ie and providing research teams with technical assistance. MJ, SS, MDAL and SSP have also worked as authors on the systematic review and MJ and SSP have been coauthors of the EGM report. Among these, only the work on the systematic review could pose a potential conflict of interest. However, several procedural safeguards and transparency measures were put in place to mitigate the risk this conflict of interest imposed. All candidate systematic reviews, including the one carried out by 3ie, have undergone a rigorous screening and critical appraisal process by two independent screeners. The authors have no financial interest in this area. MD has authored systematic reviews and systematic reviews of reviews but largely on issues related to financial inclusion. MD is also an editor of the International Development Coordinating Group at the Campbell Collaboration, but this will not pose any conflicts of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objectives: The designing of contextually tailored sustainable plans to finance the procurement of vaccines and the running of appropriate immunisation programmes are necessary to address the high burden of vaccine-preventable diseases and low immunisation coverage in sub-Saharan Africa (SSA). We sought to estimate the minimum fraction of a country's health budget that should be invested in national immunisation programmes to achieve national immunisation coverage of 80% or greater depending on the context, with and without donors' support., Design: Multicountry analysis of secondary data using retrieved publicly available data from the WHO, Global Alliance for Vaccines and Immunization (GAVI) and World Bank databases., Setting: Data on 24 SSA countries, between 2013 and 2017., Methods: We model the variations in immunisation coverage across the different SSA countries using a fractional logit model. Three different generalised linear models were fitted to explore how various explanatory variables accounted for the variability in each of the three different vaccines-measles-containing vaccine (MCV)1, diphtheria, pertussis, tetanus (DPT3) and BCG., Results: We observed an association between current health expenditure (as a percentage of gross domestic product) and immunisation coverage for BCG (OR=1.01, 95% CI: 1.01 to 1.04, p=0.008) and DPT3 (OR=1.01, 95% CI: 1.0 to 1.02, p=0.020) vaccines. However, there was no evidence to indicate that health expenditure on immunisation (as a proportion of current health expenditure) could be a strong predictor of immunisation coverage (DPT, OR 0.96 (95% CI 0.78 to 1.19; p=0.702); BCG, OR 0.91 (0.69 to 1.19; p=0.492); MCV, OR 0.91 (0.69 to 1.19; p=0.482)). We demonstrate in selected countries that to achieve the GAVI target of 80% in the countries with low DPT3 coverage, health expenditure would need to be increased by more than 45%., Conclusions: There is a need to facilitate the development of strategies that support African countries to increase domestic financing for national immunisation programmes towards achieving 2030 targets for immunisation coverage., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Pregnant women have been historically excluded from interventional research. While recent efforts have been made to improve their involvement, there remains a disparity in the evidence base for treatments available to pregnant women compared with the non-pregnant population. A significant barrier to the enrolment of pregnant women within research is risk perception and a poor understanding of decision-making in this population., Objective: Assess the risk perception and influences on decision-making in pregnant women, when considering whether to enrol in a hypothetical interventional research study., Design: Semistructured interviews were undertaken, and thematic analysis was undertaken of participant responses., Participants: Twelve pregnant women were enrolled from an antenatal outpatient clinic., Results: Participants were unanimously positive about enrolling in the proposed hypothetical interventional study. Risk perception was influenced by potential risks to their fetus and their previous experiences of healthcare and research. Participants found the uncertainty in quantifying risk for new research interventions challenging. They were motivated to enrol in research by altruism and found less invasive research interventions more tolerable., Conclusion: It is vital to understand how pregnant women balance the perceived risks and benefits of interventional research. This may help clinicians and scientists better communicate risk to pregnant women and address the ongoing under-representation of pregnant women in interventional research., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Objective: To determine the evidence for non-specific effects of the Pneumococcal and Haemophilus influenza vaccine in children aged 5 years and under., Data Sources: A key word literature search of MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials, the European Union Clinical Trials Register and ClinicalTrials.gov up to June 2023., Study Eligibility Criteria: Randomised controlled trials (RCTs), quasi-RCT or cohort studies., Participants: Children aged 5 or under., Study Appraisal and Synthesis Methods: Studies were independently screened by two reviewers, with a third where disagreement arose. Risk of bias assessment was performed by one reviewer and confirmed by a second. Results were tabulated and a narrative description performed., Results: Four articles were identified and included in this review. We found a reduction in hospitalisations from influenza A (44%), pulmonary tuberculosis (42%), metapneumovirus (45%), parainfluenza virus type 1-3 (44%), along with reductions in mortality associated with pneumococcal vaccine. No data on the Haemophilus vaccine was found., Conclusions and Implications: In this systematic review, we demonstrate that there is a reduction in particular viral infections in children aged 5 years and under who received the 9-valent pneumococcal conjugate vaccine which differ from those for which the vaccine was designed to protect against. While limited studies have demonstrated a reduction in infections other than those which the vaccine was designed to protect against, substantial clinical trials are required to solidify these findings., Prospero Registration Number: CRD42020146640., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Bronchiolitis is an acute viral infection of the lower respiratory tract. It is most commonly caused by respiratory syncytial virus. Being a common reason for hospitalisation, it affects 13-17% of all hospitalised children younger than 2 years. Only supportive therapy, including suctioning nasal secretions, water-electrolyte balance maintenance and oxygen supplementation when needed, is recommended. However, non-evidence-based diagnostic and therapeutic approaches, including the use of inhaled bronchodilators, nebulised epinephrine, and nebulised and systemic steroids, are common. The inhalation of 3% hypertonic saline is not recommended in bronchiolitis management. However, a recently published meta-analysis revealed that the inhalation of hypertonic saline can reduce the risk of hospitalisation for outpatients with bronchiolitis, while resulting in a shorter length of hospital stay and reduced severity of respiratory distress for inpatients, although the evidence is of low certainty. We aim to assess the efficacy of nebulised hypertonic saline for the treatment of children hospitalised with bronchiolitis., Methods and Analysis: This will be a randomised, double-blinded, parallel-group, controlled trial. Children younger than 2 years who are hospitalised due to bronchiolitis will be recruited from at least three paediatric departments in Poland. Bronchiolitis is defined as an apparent viral respiratory tract infection associated with airway obstruction that is manifested by at least one of following symptoms: tachypnoea, increased respiratory effort, crackles and/or wheezing. A total of 140 children will be randomised (1:1) to receive either hypertonic saline nebulisation (5 mL, three times a day) or normal saline at the same dose. The primary outcome measure will be the duration of hospitalisation., Ethics and Dissemination: The Bioethics Committee of the Lower Silesia Medical Chamber in Wroclaw approved the study protocol (4/PNDR/2023). Caregivers will receive oral and written information about the study and written informed consent will be obtained by the study physicians. The findings of the study will be submitted to a peer-reviewed journal, and abstracts will be submitted to relevant national and international conferences., Trial Registration Number: ClinicalTrials.gov Registry (NCT06069336)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate whether intravenous immunoglobulin (IVIG) improves neurological outcomes in children with encephalitis when administered early in the illness., Design: Phase 3b multicentre, double-blind, randomised placebo-controlled trial., Setting: Twenty-one hospitals in the UK., Participants: Children aged 6 months to 16 years with a diagnosis of acute or subacute encephalitis, with a planned sample size of 308., Intervention: Two doses (1 g/kg/dose) of either IVIG or matching placebo given 24-36 hours apart, in addition to standard treatment., Main Outcome Measure: The primary outcome was a 'good recovery' at 12 months after randomisation, defined as a score of≤2 on the Paediatric Glasgow Outcome Score Extended., Secondary Outcome Measures: The secondary outcomes were clinical, neurological, neuroimaging and neuropsychological results, identification of the proportion of children with immune-mediated encephalitis, and IVIG safety data., Results: 18 participants were recruited from 12 hospitals and randomised to receive either IVIG (n=10) or placebo (n=8) between 23 December 2015 and 26 September 2017. The study was terminated early following withdrawal of funding due to slower than anticipated recruitment, and therefore did not reach the predetermined sample size required to achieve the primary study objective; thus, the results are descriptive. At 12 months after randomisation, 9 of the 18 participants (IVIG n=5/10 (50%), placebo n=4/8 (50%)) made a good recovery and 5 participants (IVIG n=3/10 (30%), placebo n=2/8 (25%)) made a poor recovery. Three participants (IVIG n=1/10 (10%), placebo n=2/8 (25%)) had a new diagnosis of epilepsy during the study period. Two participants were found to have specific autoantibodies associated with autoimmune encephalitis. No serious adverse events were reported in participants receiving IVIG., Conclusions: The IgNiTE (ImmunoglobuliN in the Treatment of Encephalitis) study findings support existing evidence of poor neurological outcomes in children with encephalitis. However, the study was halted prematurely and was therefore underpowered to evaluate the effect of early IVIG treatment compared with placebo in childhood encephalitis., Trial Registration Number: Clinical Trials.gov NCT02308982; ICRCTN registry ISRCTN15791925., Competing Interests: Competing interests: MI was a trainee member on the NIHR Efficacy and Mechanism Evaluation Programme Funding Committee from October 2020 to October 2021. MA has received a grant from the NIHR in the last 36 months, for research unrelated to the submitted work. MS has been an investigator on projects funded by GlaxoSmithKline, Merck, Moderna, Pfizer, Sanofi-Pasteur, Seqirus, Symvivo and VBI Vaccines; all funds have been paid to his institute. Ava Easton is Chief Executive of the Encephalitis Society, which has previously received grants from CSL Behring (UK). Ming Lim has received grants from the GOSH charity, Boston Children’s Hospital Research Fund and Action Medical Research in the last 36 months, all for research unrelated to the submitted work. Ming Lim is co-chair of the European Paediatric Neurology Education and Training Board and works for an institution which holds research accounts with Roche (Switzerland), Octapharma (Switzerland) and Novartis (Switzerland). Tom Solomon is supported by the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, NIHR Programme Grant for Applied Research, NIHR Global Health Research on Brain Infections and the European Union’s Horizon 2020 research and innovation program ZikaPLAN. Tom Solomon is a consultant for the MHRA Vaccine Benefit Risk Expert Working Group. Angela Vincent is a consultant for Aspen NewCo Inc and has received honoraria from UCB and Alexion. L-MY was a member of the NIHR Health Technology Assessment Efficient Study Designs from November 2015 to July 2016. Andrew J Pollard is chair of the Department of Health and Social Care’s Joint committee on Vaccines and Immunisation (JCVI) and was a member of WHO’s SAGE until 1 January 2022. Oxford University has entered a partnership with AstraZenenca on COVID-19 vaccines, but Andrew Pollard does not participate in the JCVI COVID-19 committee., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Based on 2021 data, Nigeria had the second largest number of zero-dose children globally estimated at over 2.25 million, concentrated in the northern part of the country due to factors some of which are sociocultural. This study analysed the impact of the COVID-19 pandemic and response on childhood vaccination in Northern Nigeria., Methods: Using a mixed methods sequential study design in the most populous northern states of Kaduna and Kano, quantitative routine immunisation data for the period 2018-2021 and qualitative data collected through 16 focus group discussions and 40 key informant interviews were used. An adaptation of the socioecological model was used as a conceptual framework. Mean vaccination coverages and test of statistical difference in childhood vaccination data were computed. Qualitative data were coded and analysed thematically., Results: Mean Penta 1 coverage declined in Kaduna from 69.88% (SD=21.02) in 2018 to 59.54% (SD=19.14%) by 2021, contrasting with Kano where mean Penta 1 coverage increased from 51.87% (SD=12.61) to 56.32% (SD=17.62%) over the same period. Outreaches and vaccination in urban areas declined for Kaduna state by 10% over the pandemic period in contrast to Kano state where it showed a marginal increase. The two states combined had an estimated 25% of the country's zero-dose burden in 2021. Lockdowns, lack of transport and no outreaches which varied across the states were some of the factors mentioned by participants to have negatively impacted childhood vaccination. Special vaccination outreaches were among the recommendations for ensuring continued vaccination through a future pandemic., Conclusion: While further interrogating the accuracy of denominator estimates for the urban population, incorporating findings into pandemic preparedness and response will ensure uninterrupted childhood vaccination during emergencies. Addressing the identified issues will be critical to achieving and sustaining universal childhood vaccination in Nigeria., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Senegal has demonstrated catalytic improvements in national coverage rates for early childhood vaccination, despite lower development assistance for childhood vaccines in Senegal compared with other low-income and lower-middle income countries. Understanding factors associated with historical changes in childhood vaccine coverage in Senegal, as well as heterogeneities across its 14 regions, can highlight effective practices that might be adapted to improve vaccine coverage elsewhere., Design: Childhood vaccination coverage rates, demographic information and health system characteristics were identified from Senegal's Demographic and Health Surveys (DHS) and Senegal national reports for years 2005-2019. Multivariate logistic and linear regression analyses were performed to determine statistical associations of demographic and health system characteristics with respect to childhood vaccination coverage rates., Setting: The 14 administrative regions of Senegal were chosen for analysis., Participants: DHS women's survey respondents with living children aged 12-23 months for survey years 2005-2019., Outcome Measures: Immunisation with the third dose of the diphtheria-tetanus-pertussis vaccine (DTP3), widely used as a proxy for estimating immunisation coverage levels and the retention of children in the vaccine programme., Results: Factors associated with childhood vaccination coverage include urban residence (β=0.61, p=0.0157), female literacy (β=1.11, p=0.0007), skilled prenatal care (β=1.80, p<0.0001) and self-reported ease of access to care when sick, considering travel distance to a healthcare facility (β=-0.70, p=0.0009) and concerns over travelling alone (β=-1.08, p<0.0001). Higher coverage with less variability over time was reported in urban areas near the capital and the coast (p=0.076), with increased coverage in recent years in more rural and landlocked areas., Conclusions: Childhood vaccination was more likely among children whose mothers had higher literacy, received skilled prenatal care and had perceived ease of access to care when sick. Overall, vaccination coverage is high in Senegal and disparities in coverage between regions have decreased significantly in recent years., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Objectives: Vaccination averts an estimated 2-3 million deaths annually. Although vaccine coverage improvements across Africa and South Asia have remained below global targets, several countries have outperformed their peers with significant increases in coverage. The objective of this study was to examine these countries' vaccination programmes and to identify and describe critical success factors that may have supported these improvements., Design: Multiple case study design using qualitative research methods., Setting: Three countries with high routine immunisation rates: Nepal, Senegal, and Zambia., Participants: We conducted 207 key informant interviews and 71 focus group discussions with a total of 678 participants. Participants were recruited from all levels, including government officials, health facility staff, frontline workers, community health workers, and parents. Participants were recruited from both urban and rural districts in Nepal, Senegal, and Zambia., Results: Our data revealed that the critical success factors for vaccination programmes relied on the cultural, historical, and statutory context in which the interventions were delivered. In Nepal, Senegal, and Zambia, high immunisation coverage was driven by (1) strong governance structures and healthy policy environments; (2) adjacent successes in health system strengthening; (3) government-led community engagement initiatives, and (4) adaptation considering contextual factors at all levels of the health system., Conclusions: Throughout this project, our analysis returned to the importance of defining and understanding the context, governance, financing, and health systems within a country, rather than focusing on any one intervention. This paper augments findings from existing literature by highlighting how contextual factors impact implementation decisions that have led to improvements in childhood vaccine delivery. Findings from this research may help identify transferable lessons and support actionable recommendations to improve national immunisation coverage in other settings., Competing Interests: Competing interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the research reported in this paper., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Vaccine coverage remains inequitable globally. Many systematic reviews have looked at the effectiveness of strategies to improve vaccine uptake; however, these reviews frequently lack data from low and middle-income countries (LMICs), where evidence of cost-effective strategies is most valuable. This is partly because reviews often exclude non-randomised, observational or unpublished evaluations that are common in LMICs. Many reviews also exclude multicomponent interventions due to challenges isolating the effect of each component. A comprehensive mapping of multicomponent interventions implemented in LMICs would increase the visibility of studies excluded from systematic reviews and improve comparability of future evaluations by providing guidance for researchers on evaluation frameworks. This scoping review aims to identify, compare and summarise the properties and evaluation methods of multicomponent interventions to improve uptake of routine childhood vaccines in LMICs, and to assess the strengths and limitations of evaluation frameworks applied., Methods and Analysis: This review will be conducted using the Joanna Briggs Institute methodology for scoping reviews and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews guidelines. We will search the following databases: MEDLINE, Embase, PubMed, Cochrane, Eldis and Global Health (CAB Direct), Global Index Medicus, 3ie Portal, Google Scholar, COnnecting REpositories, and reference lists. One author will screen titles and abstracts and extract data from included articles using a pretested data extraction template. Uncertainties will be resolved through discussion with another author. Only studies published in English will be included for full review. We will assess the practicability, applicability, sensitivity and specificity of the evaluation frameworks used and present results using descriptive statistics, summary tables and charts., Ethics and Dissemination: Ethics approval is not required. The review will be submitted as part of a doctoral thesis, presented at conferences and published in peer-reviewed journals., Study Registration: https://osf.io/7r84g., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: There is limited in-depth research exploring persistent symptoms and conditions among children and adolescents who contracted COVID-19 illness that required hospitalisation. The main objective of this study was to conduct qualitative interviews among families who had a child hospitalised with COVID-19 illness to elucidate their child's physical, mental and social health outcomes months after initial acute infection., Design, Setting and Participants: A qualitative study that composed of in-depth interviews among families with a child hospitalised with COVID-19 illness in one large urban US paediatric healthcare system. Parents (N=25) were recruited from an ongoing quantitative study to estimate the prevalence of long COVID in children hospitalised with COVID-19 illness. During in-depth interviews, parents were invited to describe their child's post-COVID-19 symptoms and experiences. Interviews were audiotaped, transcribed and coded in NVivo., Results: Seven themes were identified concerning the child's prolonged COVID-19 experiences: (1) post-traumatic stress disorder, (2) social anxiety, (3) severe symptoms on reinfection, (4) worsened pre-existing conditions, (5) lack of insurance coverage for costly treatments, (6) access and utilisation of support systems and (7) overall resilience and recovery. Four parent-specific themes were identified: (1) fear of COVID-19 unknowns, (2) mixed messaging from health information sources, (3) schools being both a support system and a hindrance and (4) desire for and access to support systems., Conclusions: A subset of children who were hospitalised with COVID-19 illness are experiencing a range of serious mental health impacts related to persistent COVID-19 symptoms. Clinical and public health support strategies should be developed to support these children and their families as they reintegrate in school, social and community activities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Febrile infants 90 days and younger are at risk of invasive bacterial infections (bacteraemia and meningitis) and urinary tract infections. Together this is previously termed serious bacterial infection with an incidence of approximately 10-20%. The National Institute for Health and Care Excellence guidance advocates a cautious approach with most infants requiring septic screening, parenteral broad-spectrum antibiotics and hospital admission. Internationally, variations exist in the approach to febrile infants, with European and North American guidance advocating a tailored approach based on clinical features and biomarker testing. None of the available international clinical decision aids (CDAs) has been validated in the UK and Irish cohorts. The aim of the Febrile Infant Diagnostic Assessment and Outcome (FIDO) Study is to prospectively validate a range of CDAs in a UK and Irish population including CDAs that use procalcitonin testing., Methods and Analysis: The FIDO Study is a prospective multicentre mixed-methods cohort study conducted in UK and Irish hospitals. All infants aged 90 days and younger presenting with fever or history of fever (≥38°C) are eligible for inclusion. Infants will receive standard emergency clinical care without delay. Clinical data and blood samples will be collected, and consent will be obtained at the earliest appropriate opportunity using research without prior consent methodology. The performance and cost-effectiveness of CDAs will be assessed. An embedded qualitative study will explore clinician and caregiver views on different approaches to care and perceptions of risk., Ethics and Dissemination: This study was reviewed and approved by the Office for Research Ethics Committees Northern Ireland-Health and Social Care Research Ethics Committee B, Public Benefit and Privacy Panel for Health and Social Care Scotland, and Children's Health Ireland Research and Ethics Committee Ireland. The results of this study will be presented at academic conferences and in peer-reviewed publications., Trial Registration Number: NCT05259683., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: We sought to compare the incidence of early-onset sepsis (EOS) in infants ≥34 weeks' gestation identified >24 hours after birth, in hospitals using the Kaiser Permanente Sepsis Risk Calculator (SRC) with hospitals using the National Institute for Health and Care Excellence (NICE) guidance., Design and Setting: Prospective observational population-wide cohort study involving all 26 hospitals with neonatal units colocated with maternity services across London (10 using SRC, 16 using NICE)., Participants: All live births ≥34 weeks' gestation between September 2020 and August 2021., Outcome Measures: EOS was defined as isolation of a bacterial pathogen in the blood or cerebrospinal fluid (CSF) culture from birth to 7 days of age . We evaluated the incidence of EOS identified by culture obtained >24 hours to 7 days after birth. We also evaluated the rate empiric antibiotics were commenced >24 hours to 7 days after birth, for a duration of ≥5 days, with negative blood or CSF cultures., Results: Of 99 683 live births, 42 952 (43%) were born in SRC hospitals and 56 731 (57%) in NICE hospitals. The overall incidence of EOS (<72 hours) was 0.64/1000 live births. The incidence of EOS identified >24 hours was 2.3/100 000 (n=1) for SRC vs 7.1/100 000 (n=4) for NICE (OR 0.5, 95% CI (0.1 to 2.7)). This corresponded to (1/20) 5% (SRC) vs (4/45) 8.9% (NICE) of EOS cases (χ=0.3, p=0.59). Empiric antibiotics were commenced >24 hours to 7 days after birth in 4.4/1000 (n=187) for SRC vs 2.9/1000 (n=158) for NICE (OR 1.5, 95% CI (1.2 to 1.9)). 3111 (7%) infants received antibiotics in the first 24 hours in SRC hospitals vs 8428 (15%) in NICE hospitals., Conclusion: There was no significant difference in the incidence of EOS identified >24 hours after birth between SRC and NICE hospitals. SRC use was associated with 50% fewer infants receiving antibiotics in the first 24 hours of life., Competing Interests: Competing interests: CB reports grants and personal awards funded by the National Institute for Health Research, personal fees from Chiesi Pharmaceuticals and AbbVie Pharmaceuticals and is deputy chair of the NIHR Health Technology Assessment Prioritisation Committee for hospital-based care. PTH was a member of NICE CG149 guideline committee and deputy chair of NICE CG195 guideline committee. The other authors do not have any conflicts of interests to declare., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine the associations of WHO/UNICEF Joint Monitoring Program Water, Sanitation and Hygiene (WASH) Service Ladder service levels and sociodemographic factors with diarrhoeal disease among children under 5 years in Bishoftu town, Ethiopia., Design: A community-based cross-sectional study., Setting: Bishoftu town, Ethiopia, January-February 2022., Participants: A total of 1807 mothers with at least one child under 5 years were included. Sociodemographic and WASH variables were collected using a structured questionnaire. 378 drinking water samples were collected., Outcome: The response variable was diarrhoeal disease among children under 5 years., Results: The 2-week prevalence of diarrhoeal disease among children under 5 years was 14.8%. Illiteracy (adjusted OR 3.15; 95% CI 1.54 to 6.47), occupation (0.35; 0.20 to 0.62), mother's age (1.63; 1.15 to 2.31), family size (2.38; 1.68 to 3.39), wealth index (5.91; 3.01 to 11.59), residence type (1.98; 1.35 to 2.90), sex of the child (1.62; 1.17 to 2.24), child's age (3.52; 2.51 to 4.93), breastfeeding status (2.83; 1.74 to 4.59), food storage practice (3.49; 1.74 to 8.26), unimproved drinking water source (8.16; 1.69 to 39.46), limited drinking water service (4.68; 1.47 to 14.95), open defecation practice (5.17; 1.95 to 13.70), unimproved sanitation service (2.74; 1.60 to 4.67), limited sanitation service (1.71; 1.10 to 2.65), no hygiene service (3.43; 1.91 to 6.16) and limited hygiene service (2.13; 1.17 to 3.86) were significantly associated with diarrhoeal disease., Conclusion: In this study, diarrhoea among children is a significant health issue. Child's age, drinking water service, residence type and hygiene service were the largest contributors with respect to the prevalence of diarrhoeal disease. This investigation provides information that could help to inform interventions to reduce childhood diarrhoea. The findings suggest that state authorities should initiate robust WASH strategies to achieve the Sustainable Development Goal 3 agenda., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Although SARS-CoV-2 vaccines were first approved under Emergency Use Authorization by the Food and Drug Administration in late 2020 for adults, authorisation for young children 6 months to <5 years of age did not occur until 2022. These authorisations were based on clinical trials, understanding real-world vaccine effectiveness (VE) in the setting of emerging variants is critical. The primary goal of this study is to evaluate SARS-CoV-2 VE against infection among children aged >6 months and adults aged <50 years., Methods: CASCADIA is a 4-year community-based prospective study of SARS-CoV-2 VE among 3500 adults and paediatric populations aged 6 months to 49 years in Oregon and Washington, USA. At enrolment and regular intervals, participants complete a sociodemographic questionnaire. Individuals provide a blood sample at enrolment and annually thereafter, with optional blood draws every 6 months and after infection and vaccination. Participants complete weekly self-collection of anterior nasal swabs and symptom questionnaires. Swabs are tested for SARS-CoV-2 and other respiratory pathogens by reverse transcription-PCR, with results of selected pathogens returned to participants; nasal swabs with SARS-CoV-2 detected will undergo whole genome sequencing. Participants who test positive for SARS-CoV-2 undergo serial swab collection every 3 days for 21 days. Serum samples are tested for SARS-CoV-2 antibody by binding and neutralisation assays., Analysis: The primary outcome is SARS-CoV-2 infection. Cox regression models will be used to estimate the incidence rate ratio associated with SARS-CoV-2 vaccination among the paediatric and adult population, controlling for demographic factors and other potential confounders., Ethics and Dissemination: All study materials including the protocol, consent forms, data collection instruments, participant communication and recruitment materials, were approved by the Kaiser Permanente Interregional Institutional Review Board, the IRB of record for the study. Results will be disseminated through peer-reviewed publications, presentations, participant newsletters and appropriate general news media., Competing Interests: Competing interests: HYC reports consulting with Ellume, Pfizer, The Bill and Melinda Gates Foundation, Glaxo Smith Kline, and Merck. HYC received research funding from Gates Ventures, Sanofi Pasteur, and support and reagents from Ellume and Cepheid outside of the submitted work. JAE reports research support from Gates Ventures, AstraZeneca, GlaxoSmithKline, Merck, and Pfizer, and consulting with Sanofi Pasteur, AstraZeneca, Teva Pharmaceuticals, and Meissa Vaccines, outside of the submitted work. ALN reports research funding from Pfizer and Vir Biotechnology, outside of the submitted work. JLK reports research funding from Vir Biotechnology, outside of the submitted work., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Vaccine-preventable infectious diseases (VPDs) are major causes of morbidity/mortality among children under 5 years of age worldwide and in Nigeria/Ebonyi state. Routine childhood immunisation is an invaluable prevention strategy for many VPDs. Due to suboptimal coverage and untimely receipt/delay in receipt of vaccinations, outbreaks of VPDs such as measles, yellow fever, diphtheria and others continue to reoccur around the world and in Nigeria/Ebonyi state. This study aims to evaluate the effectiveness of hybrid parents and health workers adaptive intervention in increasing the optimal/timely (cumulative age-appropriate) routine childhood immunisation coverage in the communities in Ebonyi state, Nigeria., Methods and Analyses: A two-arm, parallel, open label, covariate-constrained cluster-randomised controlled trial with 1:1 allocation of 16 geographical clusters (the nearest catchment areas for at least one public primary healthcare (PHC) facility with at least 500 households or a population size of 3000) will be used to evaluate the effects of hybrid/combined parents and PHC workers adaptive engagement compared with control. The primary outcomes are the optimal/timely (cumulative age-appropriate) receipt of the recommended vaccines in the routine childhood immunisation schedule by children aged 5-9 completed months and 10-11 completed months and the age-appropriate vaccines receipt score for the recommended vaccines. The outcomes will be measured through a population-based household survey of at least 15 children aged 5-9 and 10-11 months per cluster at baseline and at the end of the study using a structured interviewer-administered questionnaire in KoBoCollect installed in android devices. All analyses will be done using a cluster-level method on as-randomised basis., Ethics and Dissemination: Ethical approval for the trial was obtained from the Ebonyi State Health Research and Ethics Committee (EBSHREC/01/06/2022-31/05/2023) and verbal consent will be obtained from participants. Study findings will be reported at local/national and international levels as appropriate., Trial Registration Number: ISRCTN59811905., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Implementation research was employed to examine rates and contextual factors associated with mothers' care-seeking for their sick neonates and identify challenges for community-based possible serious bacterial infection (PSBI) services access and implementation during the COVID-19 pandemic., Design: We conducted formative research involving household survey and programmatic qualitative study., Setting: This formative study was conducted in Dembecha and Lume woredas of Amhara and Oromia regions., Participants: Data were captured from 4262 mothers aged 15-49 years who gave live birth 2-14 months before data collection, and interviews with 18 programme managers and 16 service providers in April to May 2021., Analysis: A multilevel regression model was employed to identify predictors of maternal care-seeking for PSBI and thematic qualitative analysis to inform strategy development to strengthen PSBI implementation., Results: Overall, 12% (95% CI 11.0% to 12.9%) and 8% (95% CI 7.9% to 9.6%) of mothers reported any newborn illness and severe neonatal infection (PSBI), respectively. More than half of mothers sought formal medical care, 56% (95% CI 50.7% to 60.8%) for PSBI. Women who received postnatal care within 6 weeks (adjusted OR (AOR) 2.08; 95% CI 1.12 to 3.87) and complete antenatal care (ie, weight measured, blood pressure taken, urine and blood tested) (AOR 2.04; 95% CI 1.12 to 3.75) had higher odds of care-seeking for PSBI. Conversely, fear of COVID-19 (AOR 0.27; 95% CI 0.15 to 0.47) and residing more than 2 hours of walking distance from the health centre (AOR 0.39; 95% CI 0.16 to 0.93) were negatively associated with care-seeking for severe newborn infection. Multiple pre-existing health system bottlenecks were identified from interviews as barriers to PSBI service delivery and exacerbated by the COVID-19 pandemic., Conclusion: We found gaps in and factors associated with care-seeking behaviour of mothers for their sick young infants including fear of COVID-19 and pre-existing health system-level barriers. The findings of the study were used to design and implement strategies to mitigate COVID-19 impacts on management of PSBI., Competing Interests: Competing interests: The authors (GTT, NF, DE, WB and KE) work for JSI Research & Training Institute, a commercial company., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Objective: To estimate vaccination coverage among children under the age of five attending the paediatric emergency department (PED) using tetanus and MMR vaccination as a proxy., Design: A cross-sectional observational study with a single data collection point for each participant., Setting: A single large PED in Greater Manchester, England., Participants: Children (under 5 years old) attending the PED during October 2021. Participation was 'opt-out' and parents/carers were given until the end of the following month to request that their child's data be excluded., Primary and Secondary Outcome Measures: The primary outcome of interest was the percentage of children who were up-to-date with their routine childhood vaccinations at their time of attendance to the PED. Secondary outcome measures were the percentage of children who had received age-appropriate tetanus and MMR vaccination, and how these compared with local population data at the ages of 1, 2 and 5 years of age., Results: One-third of under-5s in this study had unmet vaccination need and were missing at least one dose of either MMR or tetanus-containing vaccine. In older age groups, many were missing their tetanus boosters and only 1 in 5 of those eligible had received two doses of MMR. Those in younger age groups had vaccination coverage levels comparable to the local data, but still below the target of 95%., Conclusions: Those children eligible for preschool boosters (tetanus and MMR2) appear to have considerable unmet vaccination need. While the pandemic has had an impact, the observation that MMR2 uptake is considerably lower than tetanus booster (when they are scheduled together) warrants further investigation. Catch-up campaigns for MMR2 should focus on this cohort of children and the PED may offer an opportunity for an intervention., Trial Registration Number: NCT04485624., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The COVID-19 pandemic highlighted the importance of keeping up to date on routine vaccinations. Throughout the pandemic, many routine vaccine programmes in Canada were paused or cancelled, including school-based immunisation programmes (SBIP). This resulted in decreased coverage for many vaccine-preventable diseases. While the effects of the pandemic on SBIP have been described in other provinces, its effects in the Maritime region (ie, Nova Scotia, New Brunswick and Prince Edward Island) have yet to be understood. We aim to determine how these programmes were affected by COVID-19 and associated public health measures in the Canadian Maritimes by (1) identifying and describing usual and interim catch-up programmes; (2) exploring stakeholders' perceptions of SBIP through interviews; and (3) designing recommendations with stakeholders to address gaps in SBIP and vaccine coverage., Methods and Analysis: A sequential, explanatory mixed methods study design will be used to address the objectives during the study period (September 2022-December 2023). First, an environmental scan will describe changes to SBIP and vaccine coverage over a period of five school years (2018/2019-2022/2023). Findings will inform semistructured interviews (n=65) with key stakeholders (eg, health officials, healthcare providers, school officials and parents and adolescents) to explore perceptions of SBIP and changes in parental vaccine hesitancy during the pandemic. These data will be integrated to design recommendations to support SBIP during two stakeholder engagement meetings. Analysis will be guided by the behaviour change wheel, a series of complementary tools and frameworks to simplify behaviour diagnosis and analysis in public health research., Ethics and Dissemination: Ethics approval for this study has been obtained from Dalhousie University's Health Sciences Research Ethics Board (Ref: 2022-6395). Informed consent will be obtained from participants prior to participating in an interview or stakeholder engagement meeting. Study findings will be disseminated through conference presentations, publications and infographics., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Vaccinations are considered to have a large impact on disease control, hence a multitude of vaccines in infancy is recommended. Retrospective studies suggest a possible relation between timing, kind or number of vaccines given in the first year of life and the subsequent incidence of allergic diseases. It must be clarified whether a causal relationship exists to ensure safety and reduce vaccine hesitancy., Methods and Analysis: Due to the high recommendation rate of vaccines, a long-term randomised controlled trial is not considered as ethically acceptable. Therefore, this study aims to observe prospectively the allergic incidence at the age of 5 years after various vaccine interventions in the early months of life.Parents of infants up to the age of 4-6 weeks will be recruited before the first recommended vaccination. Relevant prognostic factors for allergies, status of immunisation and general health will be evaluated up to the age of 5.Allergic symptoms will be assessed by the International Study of Asthma and Allergies in Childhood-questionnaire and a medical confirmation of the allergy is mandatory.The main objective is to compare the incidence of asthma, atopic dermatitis, rhinoconjunctivitis, food allergy or any of these atopies at the age of 5 between infants who were not vaccinated or were vaccinated according to recommendations in the first year of life.The sample size calculation with about 4000 participants can prove a 5% difference to the basic prevalence with about 80% power and global 5% alpha error for the five primary endpoints adjusting according to Bonferroni-Holm and assuming a rate of 10% not early vaccinated infants., Ethics and Dissemination: The study was registered (DRKS00029677) and has received approval by the ethics committee of Universität Witten/Herdecke (no. 113/2022). The results will be published., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Children with bone and joint infections are traditionally treated with intravenous antibiotics for 3-10 days, followed by oral antibiotics. Oral-only treatment has not been tested in randomised trials., Methods and Analysis: Children (3 months to 18 years) will be randomised 1:1 with the experimental group receiving high-dose oral antibiotics and the control group receiving intravenous antibiotics with a shift in both groups to standard oral antibiotics after clinical and paraclinical improvement. Children in need of acute surgery or systemic features requiring intravenous therapy, including septic shock, are excluded. The primary outcome is defined as a normal blinded standardised clinical assessment 6 months after end of treatment. Secondary outcomes are non-acute treatment failure and recurrent infection. Outcomes will be compared by a non-inferiority assumption with an inferiority margin of 5%., Ethics and Dissemination: The trial has the potential to reduce unnecessary hospitalisation and use of intravenous antibiotics in children with bone or joint infections. Due to the close follow-up, exclusion of severely ill children and predefined criteria for discontinuation of the allocated therapy, we expect the risk of treatment failure to be minimal., Trial Registration Number: NCT04563325., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To understand the perspectives of adolescents (10-19 years old), their caregivers and healthcare providers regarding factors that impact adherence to tuberculosis (TB) treatment among adolescents., Design: We conducted in-depth interviews using semistructured interview guides based on the World Health Organization (WHO)'s Five Dimensions of Adherence framework, which conceptualises adherence as being related to the health system, socioeconomic factors, patient, treatment and condition. We applied framework thematic analysis., Setting: Between August 2018 and May 2019, at 32 public health centres operated by the Ministry of Health in Lima, Peru., Participants: We interviewed 34 adolescents who completed or were lost to follow-up from treatment for drug-susceptible pulmonary TB disease in the preceding 12 months; their primary caregiver during treatment; and 15 nurses or nurse technicians who had ≥6 months' experience supervising TB treatment., Results: Participants reported numerous treatment barriers, the most common of which were the inconvenience of health facility-based directly observed therapy (DOT), long treatment duration, adverse treatment events and symptom resolution. The support of adult caregivers was critical for helping adolescents overcome these barriers and carry out the behavioural skills (eg, coping with the large pill burden, managing adverse treatment events and incorporating treatment into daily routines) needed to adhere to treatment., Conclusion: Our findings support a three-pronged approach to improve TB treatment adherence among adolescents: (1) reduce barriers to adherence (eg, home-based or community-based DOT in lieu of facility-based DOT, reducing pill burden and treatment duration when appropriate), (2) teach adolescents the behavioural skills required for treatment adherence and (3) strengthen caregivers' ability to support adolescents., Competing Interests: Competing interests: SC received an honorarium from Johnson & Johnson for a presentation on TB in youth at the World Lung Conference of the International Union Against Tuberculosis and Lung Disease (Virtual Conference, October 2021). The authors declare no other competing interests., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Inactivated, viral vector and mRNA vaccines have been used in the Nepali COVID-19 vaccination programme but there is little evidence on the effectiveness of these vaccines in this setting. The aim of this study is to describe COVID-19 vaccine effectiveness in Nepal and provide information on infections with SARS-CoV-2 variants., Methods and Analysis: This is a hospital-based, prospective test-negative case-control study conducted at Patan Hospital, Kathmandu. All patients >18 years of age presenting to Patan Hospital with COVID-19-like symptoms who have received a COVID-19 antigen/PCR test are eligible for inclusion. The primary outcome is vaccine effectiveness of licensed COVID-19 vaccines against laboratory-confirmed COVID-19 disease.After enrolment, information will be collected on vaccine status, date of vaccination, type of vaccine, demographics and other medical comorbidities. The primary outcome of interest is laboratory-confirmed SARS-CoV-2 infection. Cases (positive for SARS-CoV-2) and controls (negative for SARS-CoV-2) will be enrolled in a 1:4 ratio. Vaccine effectiveness against COVID-19 disease will be analysed by comparing vaccination status with SARS-CoV-2 test results.Positive SARS-CoV-2 samples will be sequenced to identify circulating variants and estimate vaccine effectiveness against common variants.Measuring vaccine effectiveness and identifying SARS-CoV-2 variants in Nepal will help to inform public health efforts. Describing disease severity in relation to specific SARS-CoV-2 variants and vaccine status will also inform future prevention and care efforts., Ethics and Dissemination: Ethical approval was obtained from the University of Oxford Tropical Ethics Committee (OxTREC) (ref: 561-21) and the Patan Academy of Health Sciences Institutional Review Board (ref: drs2111121578). The protocol and supporting study documents were approved for use by the Nepal Health Research Council (NHRC 550-2021). Results will be disseminated in peer-reviewed journals and to the public health authorities in Nepal., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: In the early stage of sepsis, identifying high-risk paediatric patients with a poor prognosis and providing timely and adequate treatment are critical. This study aimed to evaluate the effect of average body temperature within 24 hours of admission on the short-term prognosis of paediatric patients with sepsis., Design: A retrospective cohort study., Setting: A single-centre, tertiary care hospital in China, containing patient data from 2010 to 2018., Participants: 1144 patients with sepsis were included., Intervention: None., Primary and Secondary Outcome Measures: The main outcome measure was in-hospital mortality, which was defined as death from any cause during hospitalisation. The secondary outcome was the length of hospital stay., Results: The LOWESS method showed a roughly 'U'-shaped relationship between body temperature on the first day and in-hospital mortality. Multivariate logistic regression showed that severe hypothermia (OR 14.72, 95% CI 4.84 to 44.75), mild hypothermia (OR 3.71, 95% CI 1.26 to 10.90), mild hyperthermia (OR 3.41, 95% CI 1.17 to 9.90) and severe hyperthermia (OR 5.15, 95% CI 1.84 to 14.43) were independent risk factors for in-hospital mortality. Compared with other variables, the Wald χ 2 value of temperature on the first day minus the degree of freedom was the highest., Conclusions: Whether hypothermic or hyperthermic, the more abnormal the temperature on the first day is, the higher the risk of in-hospital death in children with sepsis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: While lower respiratory tract infections are the main cause of death for children under 5 globally, only a small proportion of children with respiratory tract infections need antibiotics. Overuse of antibiotics globally is leading to increasing rates of antibiotic resistance. In Kyrgyzstan, healthcare workers regularly prescribe antibiotics when clinical uncertainty is present to err on the side of caution. Targeting antibiotic use with biomarkers of inflammation such as C reactive protein (CRP) testing at the point-of-care test (POCT) has been shown to reduce antibiotic use in general, but only few studies have been done in children and no studies exist from Central Asia. This study aims to assess whether the use of a CRP POCT can safely decrease prescription of antibiotics for children with acute respiratory symptoms in primary level healthcare centres in Kyrgyzstan., Methods and Analysis: Multicentre, open-label, individually randomised, controlled clinical trial with 14 days follow-up (follow-up by phone on days 3, 7 and 14) in rural lowland Chui and highland Naryn regions of Kyrgyzstan. The population are children aged 6 months to 12 years attending the primary level healthcare centres during normal business hours with acute respiratory symptoms. CRP POCT equipment will be supplied to healthcare centres, along with a short training session in CRP use, including the interpretation of results to support the clinical evaluation of the child with acute respiratory infection. The primary outcomes are the proportion of patients prescribed an antibiotic within 14 days of index consultation (superiority analysis) and days to recovery (non-inferiority analysis). Secondary outcomes are antibiotics prescribed at index consultation, reconsultations, hospital admission and vital status within 14 days. Analysis of the first primary outcome, antibiotic use, will be intention to treat using a logistic regression model. Analysis of the second primary outcome, days to recovery, will be per protocol using a linear regression model and a non-inferiority margin of 1 day., Ethics and Dissemination: The study was approved on 18 June 2021 by the Ethics Committee (ref: no. 1) of the National Centre of Maternity and Childhood Care, Bishkek, Kyrgyzstan. The results of the study regardless of the conclusion will be presented at international conferences and published in peer-reviewed scientific medical journals along with policy briefs and technical reports., Trial Registration Number: NCT05195866., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To identify, characterise and map the existing knowledge about programmes that provide immunisation support to Canadians and barriers and facilitators to their delivery., Design: Scoping review and environmental scan., Introduction: Vaccine hesitancy may be associated with unmet support needs of individuals. Immunisation support programmes that provide multicomponent approaches can improve vaccine confidence and equitable access., Inclusion Criteria: Canadian programmes that focus on providing information about immunisation for the general public, but excluding articles targeting health professionals. The primary concept involves mapping the characteristics of programmes and our secondary concept examines barriers and facilitators to programme delivery., Methods: The Joanna Briggs Institute (JBI) methodology guided this review, reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. A search strategy was developed and translated for six databases in November 2021 (updated October 2022). Unpublished literature was identified through the Canadian Agency for Drugs and Technologies in Health Grey Matters checklist and other relevant sources. Stakeholders (n=124) from Canadian regional health authorities were also contacted by email for publicly accessible information. Two independent raters screened and extracted data from identified material. Results are presented in tabular form., Results: The search strategy and environmental scan resulted in 15 287 sources. A total of 161 full-text sources were reviewed after applying eligibility criteria, resulting in 50 articles. Programmes were delivered in multiple Canadian provinces, focusing on various vaccine types. All programmes aimed to increase vaccine uptake and were mostly provided in person. Multidisciplinary delivery teams based on collaborations among multiple entities were credited as a facilitator to programme delivery across settings. Limitations on programme resources, attitudes of programme staff and participants, and systems organisation were identified as barriers to delivery., Conclusions: This review highlighted characteristics of immunisation support programmes across various settings and described multiple facilitators and barriers. These findings can inform future interventions that aim to support Canadians in making decisions about immunisation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Competing interests: FR has received honoraria for consultancy and/or lectures from GSK and MSD. RM has received investigator led grants from GSK and MSD. These are paid to his institution and he does not receive any (direct or indirect) financial benefit from them. AF is a member of the Joint Committee on Vaccination and Immunisation, the UK national immunisation technical advisory group and is the chair of the WHO European Technical Advisory Group of Experts (ETAGE) on immunisation. He is the investigator in clinical vaccine trials funded by GSK and is also co-investigator of similar studies of varicella epidemiology funded by both GSK and MSD in the UK but receives no personal remuneration for this work. MR, JO, ZJ, GA and JL-B have no conflicts of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Ear pain is the most prominent symptom of childhood acute otitis media (AOM). To control the pain and reduce reliance on antibiotics, evidence of effectiveness for alternative interventions is urgently needed. This trial aims to investigate whether analgesic ear drops added to usual care provide superior ear pain relief over usual care alone in children presenting to primary care with AOM., Methods and Analysis: This is a pragmatic, two-arm, individually randomised, open, superiority trial with cost-effectiveness analysis and nested mixed-methods process evaluation in general practices in the Netherlands. We aim to recruit 300 children aged 1-6 years with a general practitioner (GP) diagnosis of AOM and ear pain. Children will be randomly allocated (ratio 1:1) to either (1) lidocaine hydrochloride 5 mg/g ear drops (Otalgan) one to two drops up to six times daily for a maximum of 7 days in addition to usual care (oral analgesics, with/without antibiotics); or (2) usual care. Parents will complete a symptom diary for 4 weeks as well as generic and disease-specific quality of life questionnaires at baseline and 4 weeks. The primary outcome is the parent-reported ear pain score (0-10) over the first 3 days. Secondary outcomes include proportion of children consuming antibiotics, oral analgesic use and overall symptom burden in the first 7 days; number of days with ear pain, number of GP reconsultations and subsequent antibiotic prescribing, adverse events, complications of AOM and cost-effectiveness during 4-week follow-up; generic and disease-specific quality of life at 4 weeks; parents' and GPs' views and experiences with treatment acceptability, usability and satisfaction., Ethics and Dissemination: The Medical Research Ethics Committee Utrecht, the Netherlands, has approved the protocol (21-447/G-D). All parents/guardians of participants will provide written informed consent. Study results will be submitted for publication in peer-reviewed medical journals and presented at relevant (inter)national scientific meetings., Trial Registration: The Netherlands Trial Register: NL9500; date of registration: 28 May 2021. At the time of publication of the study protocol paper, we were unable to make any amendments to the trial registration record in the Netherlands Trial Register. The addition of a data sharing plan was required to adhere to the International Committee of Medical Journal Editors guidelines. The trial was therefore reregistered in ClinicalTrials.gov (NCT05651633; date of registration: 15 December 2022). This second registration is for modification purposes only and the Netherlands Trial Register record (NL9500) should be regarded as the primary trial registration., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Newborns are at risk for early-onset sepsis (EOS). In the Netherlands, EOS affects less than 0.2% of newborns, but approximately 5% are treated with empirical antibiotics. These numbers form an example of overtreatment in countries using risk-factor based guidelines for administrating antibiotics. An alternative to these guidelines is the EOS calculator, a tool that calculates an individual EOS risk and provides management recommendation. However, validation outside the North-American setting is limited, especially for safety outcomes. We aim to investigate whether EOS calculator use can safely reduce antibiotic exposure in newborns with suspected EOS compared with the Dutch guideline., Methods and Analysis: This protocol describes a cluster randomised controlled trial assessing whether EOS calculator use is non-inferior regarding safety, and superior regarding limiting overtreatment, compared with the Dutch guideline. We will include newborns born at ≥34 weeks' gestation, with at least one risk factor consistent with EOS within 24 hours after birth. After 1:1 randomisation, the 10 participating Dutch hospitals will use either the Dutch guideline or the EOS calculator as standard of care for all newborns at risk for EOS. In total, 1830 newborns will be recruited. The coprimary non-inferiority outcome will be the presence of at least one of four predefined safety criteria. The coprimary superiority outcome will be the proportion of participants starting antibiotic therapy for suspected and, or proven EOS within 24 hours after birth. Secondary outcomes will be the total duration of antibiotic therapy, the percentage of antibiotic therapy started between 24 and 72 hours after birth, and parent-reported quality of life. Analyses will be performed both as intention to treat and per protocol., Ethics and Dissemination: This trial has been approved by the Medical Ethics Committee of the Amsterdam UMC (NL78203.018.21). Results will be presented in peer-reviewed journals and at international conferences., Trial Registration Number: NCT05274776., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The aim of the NONSEnse project is to investigate the non-specific effects of vaccines and immunisation programmes on the overall health of children by using information from the extensive nationwide registers on health and sociodemographic factors in Denmark, Finland, Norway and Sweden., Participants: The cohort covers 9 072 420 children aged 0-17 years, born 1990-2017/2018 and living in Denmark, Finland, Norway or Sweden. All countries use a unique identification number for its permanent residents, which makes it possible to link individual-level information from different registers., Findings to Date: Data collection and harmonisation according to a common data model was completed in March 2022. As a prerequisite for comparing the effects of childhood vaccinations on the overall health of children across the Nordic countries, we have identified indicators measuring similar levels of infectious disease morbidity across these settings. So far, studies pertaining to non-specific effects of vaccines are limited to investigations that could be undertaken using aggregated data sets that were available before the NONSEnse cohort with individual-level information was completely set up., Future Plans: We are currently performing several studies of the effects on non-targeted infectious disease morbidity across the countries following vaccination against measles, mumps, rubella, diphtheria, tetanus, pertussis, human papillomavirus, rotavirus and influenza. Multiple studies are planned within the next years using different study designs to facilitate triangulation of results and enhance causal inference., Registration: No clinical trials will be conducted within the NONSEnse project., Competing Interests: Competing interests: AAP, HN and ML are investigators in vaccine-related studies for which THL has received funding from GSK, Pfizer and Sanofi Pasteur., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To explore nurses' experiences of a tailored intervention that supported them with knowledge and tools to use during encounters and dialogue with parents with low vaccine acceptance., Design: A qualitative study with in-depth interviews conducted in 2017. Data were analysed using thematic analysis., Setting: This study was part of a multicomponent intervention targeting Somali parents and the nurses at child health centres in the Rinkeby and Tensta neighbourhoods of Stockholm. An area with documented low measles, mumps and rubella (MMR) vaccination coverage. Previous research has revealed that Somali parents in the community delayed MMR vaccination due to fear of autism despite lack of scientific evidence. The interventions were implemented in 2015-2017., Participants: Eleven nurses employed at the child health centres involved in the intervention participated in interviews. The tailored intervention targeting nurses included a series of seminars, a narrative film and an information card with key messages for distribution to parents., Results: The qualitative analysis revealed an overarching theme: perception of improved communication with parents. Two underlying themes were identified: (1) feeling more confident to address parents' MMR vaccine concerns and (2) diverse tools as useful support to dispel myth and reduce language barriers., Conclusion: From the nurses' perspective, the tailored intervention was useful to improve communication with parents having vaccine concerns. Nurses have a crucial role in vaccine uptake and acceptance. Interventions aiming to strengthen their communication with parents are therefore essential, especially in areas with lower vaccine acceptance., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate neuromotor repertoires and developmental milestones in infants exposed to antenatal COVID-19., Design: Longitudinal cohort study., Setting: Hospital-based study in Los Angeles, USA and Rio de Janeiro, Brazil between March 2020 and December 2021., Participants: Infants born to mothers with COVID-19 during pregnancy and prepandemic control infants from the Graz University Database., Interventions: General movement assessment (GMA) videos between 3 and 5 months post-term age were collected and clinical assessments/developmental milestones evaluated at 6-8 months of age. Cases were matched by gestational age, gender and post-term age to prepandemic neurotypical unexposed controls from the database., Main Outcome Measures: Motor Optimality Scores Revised (MOS-R) at 3-5 months. Presence of developmental delay (DD) at 6-8 months., Results: 239 infants were enrolled; 124 cases (83 in the USA/41 in Brazil) and 115 controls. GMA was assessed in 115 cases and 115 controls; 25% were preterm. Median MOS-R in cases was 23 (IQR 21-24, range 9-28) vs 25 (IQR 24-26, range 20-28) in controls, p<0.001. Sixteen infants (14%) had MOS-R scores <20 vs zero controls, p<0.001. At 6-8 months, 13 of 109 case infants (12%) failed to attain developmental milestones; all 115 control infants had normal development. The timing of maternal infection in pregnancy (first, second or third trimester) or COVID-19 disease severity (NIH categories asymptomatic, mild/moderate or severe/critical) was not associated with suboptimal MOS-R or DD. Maternal fever in pregnancy was associated with DD (OR 3.7; 95% CI 1.12 to 12.60) but not suboptimal MOS-R (OR 0.25; 95% CI 0.04 to 0.96)., Conclusions: Compared with prepandemic controls, infants exposed to antenatal COVID-19 more frequently had suboptimal neuromotor development., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)