Nudging towards COVID-19 and influenza vaccination uptake in medically at-risk children: EPIC study protocol of randomised controlled trials in Australian paediatric outpatient clinics.

INTRODUCTION: Children with chronic medical diseases are at an unacceptable risk of hospitalisation and death from influenza and SARS-CoV-2 infections. Over the past two decades, behavioural scientists have learnt how to design non-coercive 'nudge' interventions to encourage positive health behaviours. Our study aims to evaluate the impact of multicomponent nudge interventions on the uptake of COVID-19 and influenza vaccines in medically at-risk children. METHODS AND ANALYSES: Two separate randomised controlled trials (RCTs), each with 1038 children, will enrol a total of approximately 2076 children with chronic medical conditions who are attending tertiary hospitals in South Australia, Western Australia and Victoria. Participants will be randomly assigned (1:1) to the standard care or intervention group. The nudge intervention in each RCT will consist of three text message reminders with four behavioural nudges including (1) social norm messages, (2) different messengers through links to short educational videos from a paediatrician, medically at-risk child and parent and nurse, (3) a pledge to have their child or themselves vaccinated and (4) information salience through links to the current guidelines and vaccine safety information. The primary outcome is the proportion of medically at-risk children who receive at least one dose of vaccine within 3 months of randomisation. Logistic regression analysis will be performed to determine the effect of the intervention on the probability of vaccination uptake. ETHICS AND DISSEMINATION: The protocol and study documents have been reviewed and approved by the Women's and Children's Health Network Human Research Ethics Committee (HREC/22/WCHN/2022/00082). The results will be published via peer-reviewed journals and presented at scientific meetings and public forums. TRIAL REGISTRATION NUMBER: NCT05613751.

Priority populations' experiences of isolation, quarantine and distancing for COVID-19: protocol for a longitudinal cohort study (Optimise Study).

INTRODUCTION: Longitudinal studies can provide timely and accurate information to evaluate and inform COVID-19 control and mitigation strategies and future pandemic preparedness. The Optimise Study is a multidisciplinary research platform established in the Australian state of Victoria in September 2020 to collect epidemiological, social, psychological and behavioural data from priority populations. It aims to understand changing public attitudes, behaviours and experiences of COVID-19 and inform epidemic modelling and support responsive government policy. METHODS AND ANALYSIS: This protocol paper describes the data collection procedures for the Optimise Study, an ongoing longitudinal cohort of ~1000 Victorian adults and their social networks. Participants are recruited using snowball sampling with a set of seeds and two waves of snowball recruitment. Seeds are purposively selected from priority groups, including recent COVID-19 cases and close contacts and people at heightened risk of infection and/or adverse outcomes of COVID-19 infection and/or public health measures. Participants complete a schedule of monthly quantitative surveys and daily diaries for up to 24 months, plus additional surveys annually for up to 48 months. Cohort participants are recruited for qualitative interviews at key time points to enable in-depth exploration of people's lived experiences. Separately, community representatives are invited to participate in community engagement groups, which review and interpret research findings to inform policy and practice recommendations. ETHICS AND DISSEMINATION: The Optimise longitudinal cohort and qualitative interviews are approved by the Alfred Hospital Human Research Ethics Committee (# 333/20). The Optimise Study CEG is approved by the La Trobe University Human Ethics Committee (# HEC20532). All participants provide informed verbal consent to enter the cohort, with additional consent provided prior to any of the sub studies. Study findings will be disseminated through public website (https://optimisecovid.com.au/study-findings/) and through peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05323799.

Multicomponent interventions to improve routine childhood vaccine uptake in low and middle-income countries: a scoping review protocol.

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.

Vitamin D deficiency in South-East Asian children: a systematic review.

OBJECTIVE: To describe the prevalence and determinants of vitamin D deficiency (VDD) among healthy children aged between 0 and 18 years living in South-East Asia (SEA). DESIGN: We systematically searched Ovid MEDLINE and Ovid EMBASE for observational studies assessing VDD among healthy children in the SEA region as the primary or secondary outcome from database inception to 6 April 2021. PubMed was used for e-pubs and publications not indexed in Medline. Publications that included abstracts in English were included. We performed a systematic review to describe the prevalence of VDD in SEA children. RESULTS: Our initial search identified 550 publications with an additional 2 publications from manual screening. Of those, 21 studies from 5 different countries (Thailand, Indonesia, Vietnam, Malaysia and Cambodia) were summarised and included in forest plots. The prevalence of VDD (<50 nmol/L) ranged from 0.9% to 96.4%, with >50% of newborns having VDD, and severe VDD (<30 nmol/L) ranged from 0% to 55.8%. Female sex and urban living were the most common determinants of VDD. CONCLUSIONS: VDD among healthy children living in the SEA region is common. Efforts to detect VDD and the implementation of preventive measures, including education on safe sun exposure and oral vitamin D supplementation or food fortification, should be considered for key target groups, including adolescent females and pregnant and lactating women to improve the vitamin D status of newborns. PROTOCOL REGISTRATION NUMBER: This study is registered with PROSPERO (CRD42020181600).

Timeliness of routine childhood vaccinations in Indonesian infants in the first year of life.

BACKGROUND: Vaccines have proven to be one of the most effective strategies to control infectious diseases and contributed to childhood survival. While high vaccine coverages provide individual's and herd immunity, age-appropriate vaccination or vaccine timeliness is important for maximum vaccine's protection, but often not evaluated. We aimed to describe the timeliness of childhood vaccination for Indonesian infants and identify risk factors associated with delayed vaccination. METHODS: This study was a sub-study of the Indonesian Pneumonia and Vitamin D status (IPAD) study, a community-based cohort study to investigate pneumonia incidence in two districts in Yogyakarta province, Indonesia. Socio-demographic data were obtained from structured interviews and vaccine status was obtained from maternal and child health records. Timely vaccination was defined if the vaccine was received between four days or less before and within 28 days after the recommended age of vaccination. RESULTS: 359 (85%) out of 422 IPAD participants and their immunisation records were included. Between December 2015 and December 2017, vaccination coverage was high and ranged from 96.1% (Measles) to 100% (DTP-HepB-Hib 1). However, two thirds (67%, 242/359) of all participants had received either early or late vaccines, with dose 2 IPV (40%, 143/356), dose 3 IPV (56%, 196/349) and dose 3 DTP-HepB-Hib (29%, 103/354) most delayed, and only 1% received early doses. The main risk factors for untimely vaccination were if the infant was born in a private practice versus in a public health facility (AOR 1.90; 95% CI: 1.18-3.07) and rural residence (AOR 1.84; 95% CI: 1.15-2.94). CONCLUSIONS: Despite high vaccine coverage for Indonesian infants (>95%), two thirds (67%) of infants had untimely vaccinations, with dose 3 IPV (56%) the most delayed. Future strategies should focus on coordination between government, health care providers, and carers to ensure timely access and vaccination of infants to ensure adherence to vaccination schedules.

Intent to Be Vaccinated against COVID-19 in Victoria, Australia.

BACKGROUND: High vaccine uptake requires strong public support, acceptance, and willingness. METHODS: A longitudinal cohort study gathered survey data every four weeks between 1 October 2020 and 9 November 2021 in Victoria, Australia. Data were analysed for 686 participants aged 18 years and older. RESULTS: Vaccine intention in our cohort increased from 60% in October 2020 to 99% in November 2021. Vaccine intention increased in all demographics, but longitudinal trends in vaccine intention differed by age, employment as a healthcare worker, presence of children in the household, and highest qualification attained. Acceptance of vaccine mandates increased from 50% in October 2020 to 71% in November 2021. Acceptance of vaccine mandates increased in all age groups except 18-25 years; acceptance also varied by gender and highest qualification attained. The main reasons for not intending to be vaccinated included safety concerns, including blood clots, and vaccine efficacy. CONCLUSION: COVID-19 vaccination campaigns should be informed by understanding of the sociodemographic drivers of vaccine acceptance to enable socially and culturally relevant guidance and ensure equitable vaccine coverage. Vaccination policies should be applied judiciously to avoid polarisation.

Using provider-parent strategies to improve influenza vaccination in children and adolescents with special risk medical conditions: a randomised controlled trial protocol.

INTRODUCTION: Influenza immunisation is a highly cost-effective public health intervention. Despite a comprehensive National Immunisation Program, influenza vaccination in children and adolescents with special risk medical conditions (SRMCs) is suboptimal. Flutext-4U is an innovative, multi-component strategy targeting paediatric hospitals, general practice and parents of children and adolescents with SRMC. The Flutext-4U study aims to assess the impact of Flutext-4U to increase influenza immunisation in children and adolescents with SRMC. METHODS AND ANALYSIS: This is a randomised controlled trial involving parents of children and adolescents (aged >6 months to <18 years) with SRMC receiving tertiary care at the Women's and Children's Hospital (WCH), Adelaide, South Australia, who are eligible for funded influenza immunisation with a hospital appointment between the start of the seasonal influenza vaccination season and 31 July 2021, their treating general practitioners (GPs), and WCH paediatric specialists.Parents (of children/adolescents with SRMC) are randomised (1:1 ratio) to standard care plus intervention (SMS reminder messages to parents; reminders (written correspondence) for their child's GP from the hospital's Paediatric Outpatients Department) or standard care (hospital vaccine availability, ease of access and reminders for WCH subspecialists) with randomisation stratified by age-group (<5, 5-14, >14 to <18 years).The primary outcome is influenza vaccination, as confirmed by the Australian Immunisation Register.The proportion vaccinated (primary outcome) will be compared between randomised groups using logistic regression, with adjustment made for age group at randomisation. The effect of treatment will be described using an OR with a 95% CI. ETHICS AND DISSEMINATION: The protocol and all study materials have been reviewed and approved by the Women's and Children's Health Network Human Research Ethics Committee (HREC/20/WCHN/5). Results will be disseminated via peer-reviewed publication and at scientific meetings, professional and public forums. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12621000463875).

Vitamin D deficiency and severity of pneumonia in Indonesian children.

OBJECTIVE: To determine the prevalence of vitamin D deficiency in Indonesian children hospitalized with pneumonia and evaluate the association between vitamin D status and severity of pneumonia. METHODS: A hospital-based cross-sectional study was conducted from February 2016 to July 2017 in two district hospitals in Yogyakarta province, Indonesia. Infants and young children aged 2-59 months hospitalized with pneumonia were recruited. Serum blood samples were collected on admission and analyzed for total serum 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2 concentrations using liquid chromatography-tandem mass spectrometry. Vitamin D deficiency was defined as a level of serum vitamin D <50 nmol/L. The association between vitamin D deficiency and severity of hospitalized pneumonia according to WHO criteria, including the presence of danger signs, hypoxemia (SpO2 in air below 90%), duration of hospitalization, and admission to Intensive Care Unit (ICU), was analyzed using logistic regression. RESULTS: 133 children with WHO-defined pneumonia were enrolled in the study and 127 (96%) had their vitamin D status determined. The mean vitamin D concentration was 67 (± 24 SD) nmol/L and 19% of participants were vitamin D deficient. Age younger than 6 months was associated with prolonged hospitalization (> 5 days) and low birth weight and poor nutritional status on admission were risk factors for hypoxemia. However, vitamin D status was not associated with the presence of danger signs, duration of hospitalization, or hypoxemia. CONCLUSIONS: One in every five children hospitalized with pneumonia was vitamin D deficient. Vitamin D status was not associated with the severity of pneumonia.

The incidence of acute respiratory infection in Indonesian infants and association with vitamin D deficiency.

BACKGROUND: Vitamin D deficiency has been associated with acute respiratory infection (ARI) in early life, but this has not been evaluated in Indonesia. We aimed to determine the incidence of ARI in Indonesian infants, and to evaluate the association with vitamin D deficiency. METHODS: From 23 December 2015 to 31 December 2017, we conducted a community-based prospective cohort study in Yogyakarta province. We enrolled 422 pregnant women and followed their infants from birth until 12 months of age for ARI episodes. Vitamin D status was measured at birth and at age six months. We performed Cox proportional hazard regression analysis to evaluate the association between vitamin D deficiency and pneumonia incidence. RESULTS: At study completion, 95% (400/422) of infants retained with a total of 412 child years of observation (CYO). The incidence of all ARI and of WHO-defined pneumonia was 3.89 (95% CI 3.70-4.08) and 0.25 (95% CI 0.21-0.30) episodes per CYO respectively. Vitamin D deficiency at birth was common (90%, 308/344) and associated with more frequent episodes of ARI non-pneumonia (adjusted odds ratio 4.48, 95% CI:1.04-19.34). Vitamin D status at birth or six months was not associated with subsequent pneumonia incidence, but greater maternal sun exposure during pregnancy was associated with a trend to less frequent ARI and pneumonia in infants. CONCLUSION: ARI, pneumonia, and vitamin D deficiency at birth were common in Indonesian infants. Minimising vitamin D deficiency at birth such as by supplementation of mothers or safe sun exposure during pregnancy has the potential to reduce ARI incidence in infants in this setting.

The prevalence and determinants of vitamin D deficiency in Indonesian infants at birth and six months of age.

BACKGROUND: Vitamin D deficiency in infants has been associated with an increased risk of a number of diseases but there are limited data on the prevalence and determinants of vitamin D deficiency from tropical settings with high infant morbidity and mortality. OBJECTIVE: To determine the prevalence and determinants of vitamin D deficiency in infants at birth and at six months of age in Yogyakarta province, Indonesia. DESIGN: Serum vitamin D of eligible infants was measured in cord blood at birth and at six months of age. Factors associated with vitamin D deficiency (serum 25-hydroxyvitamin D <50 nmol/L) were collected prospectively monthly from birth and concentrations measured by liquid chromatography-tandem mass spectrometry. Independent risk factors were identified by multiple logistic regression. RESULTS: Between December 2015 to December 2017, 350 maternal-newborn participants were recruited and followed up. Vitamin D deficiency was detected in 90% (308/344) of cord blood samples and 13% (33/255) of venous blood samples at six months. Longer time outdoors (≥2 hours per day) and maternal multivitamin intake containing vitamin D during pregnancy were protective against vitamin D deficiency at birth (AOR: 0.10, 95% CI: 0.01-0.90 and AOR: 0.21, 95% CI: 0.06-0.68, respectively). Risk factors for vitamin D deficiency at six months included lower cumulative skin-sun exposure score (AOR: 1.12, 95% CI: 1.04-1.20), severe vitamin D deficiency at birth (AOR: 7.73, 95% CI: 1.20-49.60) and exclusive breastfeeding (AOR: 2.64, 95% CI: 1.07-6.49) until six months. Among exclusively breast fed (EBF) infants, a higher skin-sun exposure score was associated with reduced vitamin D deficiency risk. CONCLUSION: In equatorial regions, the role of 'safe' morning sun exposure in infants and mothers in populations with medium to dark brown skin pigmentation and effective interventions to prevent vitamin D deficiency in newborns and EBF infants, need further consideration and evaluation.

Costs and uptake of a community model of paediatric food allergy care versus specialist hospital care: A before-and-after controlled trial.

AIM: To compare the costs of community-based food allergy model of care (intervention cohort, IC) with a tertiary-hospital, specialist allergy clinic model of care (control cohort, CC). METHODS: In this pragmatic controlled trial, children (aged 0-12 years) newly referred to the allergy clinic at Melbourne's Royal Children's Hospital with suspected/known food allergy to three or fewer foods were allocated to see either a community-based paediatrician, trained via online webinars and web-based clinical decision support tools for food allergy diagnosis and management, or a hospital allergist. Per-patient costs to the health-care system and out-of-pocket costs to families seen within 12 months (clinician time, allergy tests and medicare billing) were compared between the two models of care. RESULTS: At 12 months, 54/181 (30%) CC families had been seen in the allergy clinic and 93/115 (81%) of the IC families who chose to see a community paediatrician had been seen. In an intention-to-treat analysis (ITT), health-care system costs per IC patient were higher than the costs per CC patient (mean cost $333 versus $319, respectively; mean difference $14, 95% Confidence Interval (CI) -97 to 118, P = 0.81). Total out-of-pocket costs to family were $129 in the IC compared with $89 in the CC (mean difference $40, 95% CI $4-$77, P = 0.03). CONCLUSIONS: A community-based model of care for simple food allergy showed that costs to the health-care system were similar between the community model and hospital care but did not show reduced out-of-pocket costs to the families 12-months post-enrolment.

Instruments that measure psychosocial factors related to vaccination: a scoping review protocol.

INTRODUCTION: As vaccine-preventable disease outbreaks increase, there is growing international interest in monitoring public attitudes towards vaccination and implementing and evaluating vaccine promotion interventions. Outcome selection and measurement are central to intervention evaluation. Measuring uptake rates alone cannot determine which elements in a multicomponent vaccine-promotion intervention are most effective, why specific populations are undervaccinated or when confidence in vaccines is wavering. To develop targeted and cost-effective interventions and policies, it is necessary to measure vaccination-related psychosocial factors such as knowledge, attitudes and aspects of decision-making. This scoping review aims to identify, compare and summarise the properties and validation of instruments for measuring vaccination-related psychosocial factors and identify gaps where no instruments exist. METHODS AND ANALYSIS: We will search Medline OVID, Embase OVID, CINAHL and PsycINFO with no date restriction, using a pilot-tested search strategy of terms related to vaccination: knowledge, attitudes, trust, acceptance and decision-making and measurement, psychometric testing or validation. This search will be supplemented with manual search and expert consultation. We will include studies that describe instrument development, adaptation or testing and include evaluation of at least two measurement properties (eg, content, criterion, or construct validity; test-retest reliability; internal consistency; sensitivity; responsiveness). Instruments measuring a vaccination-related psychosocial factor in any population will be included. All studies will be screened by one reviewer, with a sample double-screened to confirm accuracy. Disagreements will be resolved with a third reviewer. Data will be synthesised narratively and through summary tables to chart and compare instrument characteristics such as factors measured, date and/or location of development or validation, measurement properties evaluated and population. ETHICS AND DISSEMINATION: This scoping review aims to provide an overview of existing instruments and ascertain measurement gaps where no measurement instruments currently exist. The identified instruments will form the basis of an open-access online repository of instruments.

The ORVAC trial protocol: a phase IV, double-blind, randomised, placebo-controlled clinical trial of a third scheduled dose of Rotarix rotavirus vaccine in Australian Indigenous infants to improve protection against gastroenteritis.

INTRODUCTION: Rotavirus vaccines were introduced into the Australian National Immunisation Program in 2007. Despite this, Northern Territory Indigenous children continue to be hospitalised with rotavirus at a rate more than 20 times higher than non-Indigenous children in other Australian jurisdictions, with evidence of waning protection in the second year of life. We hypothesised that scheduling an additional (third) dose of oral human rotavirus vaccine (Rotarix, GlaxoSmithKline) for children aged 6 to <12 months would improve protection against clinically significant all-cause gastroenteritis. METHODS AND ANALYSIS: This Bayesian adaptive clinical trial will investigate whether routinely scheduling an additional dose of Rotarix for Australian Indigenous children aged 6 to <12 months old confers significantly better protection against clinically important all-cause gastroenteritis than the current two-dose schedule at 2 and 4 months old. There are two coprimary endpoints: (1) seroconversion from baseline serum anti-rotavirus immunoglobulin A (IgA) titre <20 U/mL prior to an additional dose of Rotarix/placebo to serum anti-rotavirus IgA titre >20 U/mL following the administration of the additional dose of Rotarix/placebo and (2) time from randomisation to medical attendance (up to age 36 months old) for which the primary reason is acute gastroenteritis/diarrhoea. Secondary endpoints include the change in anti-rotavirus IgA log titre, time to hospitalisation for all-cause diarrhoea and for rotavirus-confirmed gastroenteritis/diarrhoea, and rotavirus notification. Analysis will be based on Bayesian inference with adaptive sample size. ETHICS, REGISTRATION AND DISSEMINATION: Ethics approval has been granted by Central Australian Human Research Ethics Committee (HREC-16-426) and Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research (HREC-2016-2658). Study investigators will ensure the trial is conducted in accordance with the principles of the Declaration of Helsinki and with the ICH Guidelines for Good Clinical Practice. Individual participant consent will be obtained. Results will be disseminated via peer-reviewed publication. The trial is registered with Clinicaltrials.gov (NCT02941107) and important modifications to this protocol will be updated. TRIAL REGISTRATION NUMBER: NCT02941107; Pre-results.

Catching up with catch-up: a policy analysis of immunisation for refugees and asylum seekers in Victoria.

This study examines catch-up immunisation for people of refugee-like background in Victoria, exploring effective models of service delivery to complete catch-up vaccinations. The analysis is based on: (i) review of the medical literature, Commonwealth and Victorian government immunisation policy and immunisation patient information; (ii) review of vaccination coverage and service delivery data; and (iii) stakeholder interviews completed in 2014 with 45 people from 34 agencies, including 9 local government areas in Victoria. Although refugees and asylum seekers all need catch-up vaccinations on arrival, they face significant barriers to completing immunisation in Australia. Analysis suggests missed opportunities by service providers and perceptions that catch-up vaccination is time-consuming, difficult and resource-intensive. Service delivery is fragmented across primary care and local government, and pathways depend on age, location and healthcare access. There are strengths, but also limitations in all current service delivery models. Gaps in vaccine funding for refugee-like populations have now been addressed through Commonwealth initiatives, however migration is still not well considered in immunisation policy, and existing systems for notification payments do not capture catch-up vaccination for these groups. Providers identify areas for improvement in professional development and support, patient information, patient-held records and immunisation surveillance data.

The clinical, immunological and microbiological impact of the 10-valent pneumococcal-Protein D conjugate vaccine in children with recurrent protracted bacterial bronchitis, chronic suppurative lung disease and bronchiectasis: A multi-centre, double-blind, randomised controlled trial.

We aimed to determine the efficacy of the 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in children aged 18-months to <18-years with recurrent protracted bacterial bronchitis (rPBB), chronic suppurative lung disease (CSLD) or bronchiectasis. In a multi-centre, double-blind randomised controlled trial, children received two doses, 2-months apart of the 10vPHiD-CV or quadrivalent meningococcal-ACYW135 conjugate vaccine. Active surveillance for acute exacerbations, respiratory symptoms and antibiotic use was undertaken through to 12-months after the second vaccine dose (clinical cohort only). Serum, saliva and nasopharyngeal swabs were collected to measure immunological and microbiological effects (immunology cohort). Between December 2012 and August 2015, 62 children were enrolled onto the clinical protocol (1 excluded from clinical analyses due to unblinding), while 74 contributed to the immunology cohort (overall mean age = 6.8-years (standard deviation = 3.7), 42 (56.8%) male). The absolute risk difference comparing the 10vPHiD-CV group (n = 31 children) to the MenACYW135 group (n = 30 children) for acute exacerbations was -0.5 exacerbations/100-weeks at risk (95% confidence interval (CI) -2.0, 0.9). Compared to the MenACYW135 group, children who received the 10vPHiD-CV were less likely to have respiratory symptoms in each fortnight of surveillance (incidence density ratio (IDR) 0.82, 95%CI 0.61, 1.10) and required fewer short-course (<14-days duration) antibiotics (IDR 0.81, 95% CI 0.61, 1.09). The vaccine was immunogenic and no serious adverse events related to the vaccine were reported. In conclusion, 10vPHiD-CV might have a future role in managing children with rPBB, CSLD and bronchiectasis, but larger multicentre trials are needed to confirm or refute findings from this preliminary study.

Rotavirus specific maternal antibodies and immune response to RV3-BB neonatal rotavirus vaccine in New Zealand.

BACKGROUND: Maternal antibodies, acquired passively via placenta and/or breast milk, may contribute to the reduced efficacy of oral rotavirus vaccines observed in children in developing countries. This study aimed to investigate the effect of rotavirus specific maternal antibodies on the serum IgA response or stool excretion of vaccine virus after any dose of an oral rotavirus vaccine, RV3-BB, in parallel to a Phase IIa clinical trial conducted at Dunedin Hospital, New Zealand. At the time of the study rotavirus vaccines had not been introduced in New Zealand and the burden of rotavirus disease was evident. METHODS: Rotavirus specific IgG and serum neutralizing antibody (SNA) levels in cord blood and IgA levels in colostrum and breast milk samples collected ∼4 weeks, ∼20 weeks and ∼28 weeks after birth were measured. Infants were randomized to receive the first dose of vaccine at 0-5 d (neonatal schedule) or 8 weeks (infant schedule). Breast feeding was with-held for 30 minutes before and after vaccine administration. The relationship between rotavirus specific IgG and SNA levels in cord blood and IgA in colostrum and breast milk at the time of first active dose of RV3-BB vaccine and level of IgA response and stool excretion after 3 doses of vaccine was assessed using linear and logistic regression. RESULTS: Forty infants received 3 doses of RV3-BB rotavirus vaccine and were included in the analysis of the neonatal and infant groups. Rotavirus specific IgA in colostrum (neonatal schedule group) and breast milk at 4 weeks (infant schedule group) was identified in 14/21 (67%) and 14/17 (82%) of infants respectively. There was little evidence of an association between IgA in colostrum or breast milk IgA at 4 weeks, or between cord IgG or SNA level, and IgA response or stool excretion after 3 doses of RV3-BB, or after one dose (neonatal schedule) (all p>0.05). CONCLUSIONS: The level of IgA in colostrum or breast milk and level of placental IgG and SNA did not impact on the serum IgA response or stool excretion following 3 doses of RV3-BB Rotavirus Vaccine administered using either a neonatal or infant schedule in New Zealand infants.

Managing simple food allergy in community settings: A pilot study investigating a new model of care.

AIM: The prevalence of food allergy in Australia has increased, paralleled by an increase in waiting time to access tertiary paediatric allergy care. We aimed to test whether a new model of care, based on serum specific IgE testing, was feasible and acceptable to Australian families. METHODS: A prospective pilot intervention study was conducted in community paediatric practices within 20-40 km of The Royal Children's Hospital, Melbourne. Children ≤7 years with likely food allergy referred to the Department of Allergy and Immunology at RCH were included; children with anaphylaxis, drug allergy or complex food allergy (>three food groups) were excluded. Community general paediatricians, recruited through the Australian Paediatric Research Network, were trained via webinars on the management of four common food allergy-related scenarios. Paediatrician and child and family parameters were assessed at baseline and 3 months, including safety. RESULTS: 34/45 (76%) eligible families and 10/12 (83%) paediatricians participated. Paediatricians managed 27/34 (80%) of children independently, with 7/34 (20%) requiring referral to an allergist for more complex food allergy. Paediatricians reported improved knowledge and competency in managing food allergy: (mean (standard deviation) scores pre = 35 (5.3) and post = 43.3 (3.9) training). The majority of children received appropriate management; there were no anaphylaxis episodes. There was no significant change in child quality of life or parent mental health. CONCLUSIONS: Management of simple food allergy by community paediatricians appears feasible and acceptable to paediatricians and families alike. Future research will evaluate this approach in an adequately powered and controlled trial.

Safety and immunogenicity of RV3-BB human neonatal rotavirus vaccine administered at birth or in infancy: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Despite the success of rotavirus vaccines, suboptimal vaccine efficacy in regions with a high burden of disease continues to present a challenge to worldwide implementation. A birth dose strategy with a vaccine developed from an asymptomatic neonatal rotavirus strain has the potential to address this challenge and provide protection from severe rotavirus disease from birth. METHODS: This phase 2a randomised, double-blind, three-arm, placebo-controlled safety and immunogenicity trial was undertaken at a single centre in New Zealand between Jan 13, 2012, and April 17, 2014. Healthy, full-term (≥36 weeks gestation) babies, who weighed at least 2500 g, and were 0-5 days old at the time of randomisation were randomly assigned (1:1:1; computer-generated; telephone central allocation) according to a concealed block randomisation schedule to oral RV3-BB vaccine with the first dose given at 0-5 days after birth (neonatal schedule), to vaccine with the first dose given at about 8 weeks after birth (infant schedule), or to placebo. The primary endpoint was cumulative vaccine take (serum immune response or stool shedding of vaccine virus after any dose) after three doses. The immunogenicity analysis included all randomised participants with available outcome data. This trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611001212943. FINDINGS: 95 eligible participants were randomised, of whom 89 were included in the primary analysis. A cumulative vaccine take was detected in 27 (90%) of 30 participants in the neonatal schedule group after three doses of RV3-BB vaccine compared with four (13%) of 32 participants in the placebo group (difference in proportions 0·78, 95% CI 0·55-0·88; p<0·0001). 25 (93%) of 27 participants in the infant schedule group had a cumulative vaccine take after three doses compared with eight (25%) of 32 participants in the placebo group (difference in proportions 0·68, 0·44-0·81; p<0·0001). A serum IgA response was detected in 19 (63%) of 30 participants and 20 (74%) of 27 participants, and stool shedding of RV3-BB was detected in 21 (70%) of 30 participants and 21 (78%) of 27 participants in the neonatal and infant schedule groups, respectively. The frequency of solicited and unsolicited adverse events was similar across the treatment groups. RV3-BB vaccine was not associated with an increased frequency of fever or gastrointestinal symptoms compared with placebo. INTERPRETATION: RV3-BB vaccine was immunogenic and well tolerated when given as a three-dose neonatal or infant schedule. A birth dose strategy of RV3-BB vaccine has the potential to improve the effectiveness and implementation of rotavirus vaccines. FUNDING: Australian National Health and Medical Research Council, the New Zealand Health Research Council, and the Murdoch Childrens Research Institute.