Herpes simplex virus in infancy: Evaluation of national surveillance case capture.

AIM: As herpes simplex virus (HSV) in infancy is not a mandatory notifiable condition in Australia, completeness of ascertainment by the Australian Paediatric Surveillance Unit (APSU) has been difficult to evaluate to date. We evaluated case capture in Queensland (QLD) and Western Australia (WA) using statewide laboratory and clinical data and complementary surveillance data collected via the APSU. METHODS: HSV polymerase chain reaction positive results in infants (0-3 months) from 2007 to 2017 were obtained from statewide public pathology providers in QLD and WA. Clinical data were extracted from patient records and compared to APSU reported cases. RESULTS: A total of 94 cases of HSV disease in infancy (70 QLD; 24 WA) were identified from laboratory data sets, compared to 36 cases (26 QLD; 10 WA) reported to the APSU. In total there was 102 unique cases identified; 28 cases were common to both data sets (seven skin eye mouth (SEM) disease, 13 central nervous system (CNS) disease and eight disseminated disease). Active surveillance captured 35% (36/102) of cases overall including 74% (14/19) of CNS, 71% (10/14) of disseminated and 17% (12/69) of SEM disease cases, respectively. Surveillance reported cases had a higher case-fatality rate compared to those not reported (14% vs. 3%, P = 0.038). Neurological sequelae at discharge were comparable between the groups. CONCLUSION: Active surveillance captures one third of hospitalised HSV cases in QLD and WA, including the majority with severe disease. However, morbidity and mortality remain high. Future studies on HSV will rely on observational studies. Enhanced case ascertainment through combined laboratory and surveillance data is essential for better understanding and improving outcomes.

Assessing the Impact of Pneumococcal Conjugate Vaccine Immunization Schedule Change From 3+0 to 2+1 in Australian Children: A Retrospective Observational Study.

BACKGROUND: In mid-2018, the Australian childhood 13-valent pneumococcal conjugate vaccine schedule changed from 3+0 to 2+1, moving the third dose to 12 months of age, to address increasing breakthrough cases of invasive pneumococcal disease (IPD), predominantly in children aged >12 months. This study assessed the impact of this change using national IPD surveillance data. METHODS: Pre- and postschedule change 3-dose 13-valent pneumococcal conjugate vaccine breakthrough cases were compared by age group, serotype, and clinical syndrome. Annual rates of breakthrough cases were calculated (per 100 000) using respective birth cohort sizes and 3-dose vaccine coverage. Using time-series modelling, observed IPD rates in children aged <12 years were compared to that expected if the 3+0 schedule were continued. FINDINGS: Over 2012-2022, rate of 3-dose breakthrough cases in children aged >12 months was 2.8 per 100 000 (n = 557; 11 birth cohorts). Serotype 3 replaced 19A as predominant breakthrough serotype (respectively, 24% and 65% in 2013 to 60% and 20% in 2022) followed by 19F. In breakthrough cases, the most frequent clinical phenotype was bacteremic pneumonia (69%), with meningitis accounting for 3%-4%. In cohorts eligible for 2+1 versus 3+0 schedules, rate of breakthrough cases was lower for all vaccine serotypes, except type 3 (incidence rate ratio, 0.50 [95% confidence interval, .28-.84] and 1.12 [0.71-1.76], respectively). Observed compared to expected IPD was 51.7% lower (95% confidence interval, -60.9 to -40.7%) for vaccine serotypes, but the change for nonvaccine types was not significant 12% (-9.6 to 39.7). INTERPRETATIONS: The 2+1 schedule is likely superior to 3+0 for overall IPD control, a finding that may be worth consideration for other countries considering or using 3+0 PCV schedules.

Characterization of gram-negative bloodstream infections in hospitalised Australian children and their clinical outcomes.

BACKGROUND: Gram-negative bloodstream infections (GNBSI) more commonly occur in children with comorbidities and are increasingly associated with antimicrobial resistance. There are few large studies of GNBSI in children that relate the clinical presentation, pathogen characteristics and outcomes. METHODS: A 3-year prospective study of GNBSI in children aged <18 years was conducted in five Australian children's hospitals between 2019-2021. The clinical characteristics, disease severity and outcomes were recorded. Causative pathogens underwent antibiotic susceptibility testing and whole genome sequencing. RESULTS: There were 931 GNBSI episodes involving 818 children. Median age was 3 years (IQR 0.6-8.5). 576/931 episodes (62%) were community onset though 661/931 (71%) occurred in children with comorbidities and a central venous catheter (CVC) was present in 558/931 (60%). CVC (145/931) and urinary tract (149/931) were the most common sources (16% each). 100/931 (11%) children required Intensive Care Unit (ICU) admission and a further 11% (105/931) developed GNBSI in ICU. 659/927 (71%) isolates were Enterobacterales of which 22% (138/630) were third generation cephalosporin resistant (3GCR). Extended spectrum beta-lactamase genes (ESBL) were confirmed in 65/138 (47%) 3GCR-Enterobacterales. Most common ESBL genes were blaCTX-M-15 (34/94, 36%) and blaSHV-12 (10/94, 11%). There were 48 deaths overall and 30-day in-hospital mortality was 3% (32/931). Infections with 3GCR Enterobacterales were independently associated with higher mortality (adjusted OR 3.2, 95%CI 1.6-6.4). CONCLUSION: GNBSI in children are frequently healthcare-associated and affect children under 5 years. Infections with 3GCR Enterobacterales were associated with worse outcomes. These findings will inform optimal management guidelines and help prioritise future antimicrobial clinical trials.

The Changing Detection Rate of Respiratory Syncytial Virus in Adults in Western Australia between 2017 and 2023.

The incidence of respiratory syncytial virus (RSV) in adults is inadequately defined and the impact of SARS-CoV-2-related non-pharmaceutical interventions (NPIs) is underexplored. Using laboratory data, we described the detection rate of RSV in adults ≥16 years in Western Australia (WA) between 2017 and 2023. With the exception of 2020, RSV detections rose annually between 2017 and 2023, reaching 50.7 per 100,000 in 2023 (95% confidence interval [CI], 47.9-53.8). RSV testing expanded considerably across the study period, with the testing in 2023 more than five times the 2017 total. The detection rate was highest in adults ≥60 years between 2017 and 2019, particularly those ≥75 years. Following 2020, the detections in all age groups increased, with the highest detection rate in 2023 in those ≥75-years (199.5 per 100,000; 95% CI, 180.5-220). NPIs significantly impacted RSV seasonality; the preceding winter pattern was disrupted, resulting in an absent 2020 winter season and two major summer seasons in 2020/21 and 2021/22. The RSV season began to realign in 2022, reverting to a winter seasonal pattern in 2023 and the largest season in the study period. Ongoing surveillance will be required to understand the stability of these increases and to delineate the impact of new immunisation strategies.

Clinical predictors of hypoxic pneumonia in children from the Eastern Highlands Province, Papua New Guinea: secondary analysis of two prospective observational studies.

Background: Pneumonia is the leading cause of death in young children globally and is prevalent in the Papua New Guinea highlands. We investigated clinical predictors of hypoxic pneumonia to inform local treatment guidelines in this resource-limited setting. Methods: Between 2013 and 2020, two consecutive prospective observational studies were undertaken enrolling children 0-4 years presenting with pneumonia to health-care facilities in Goroka Town, Eastern Highlands Province. Logistic regression models were developed to identify clinical predictors of hypoxic pneumonia (oxygen saturation <90% on presentation). Model performance was compared against established criteria to identify severe pneumonia. Findings: There were 2067 cases of pneumonia; hypoxaemia was detected in 36.1%. The strongest independent predictors of hypoxic pneumonia were central cyanosis on examination (adjusted odds ratio [aOR] 5.14; 95% CI 3.47-7.60), reduced breath sounds (aOR 2.92; 95% CI 2.30-3.71), and nasal flaring or grunting (aOR 2.34; 95% CI 1.62-3.38). While the model developed to predict hypoxic pneumonia outperformed established pneumonia severity criteria, it was not sensitive enough to be clinically useful at this time. Interpretation: Given signs and symptoms are unable to accurately detect hypoxia, all health care facilities should be equipped with pulse oximeters. However, for the health care worker without access to pulse oximetry, consideration of central cyanosis, reduced breath sounds, nasal flaring or grunting, age-specific tachycardia, wheezing, parent-reported drowsiness, or bronchial breathing as suggestive of hypoxaemic pneumonia, and thus severe disease, may prove useful in guiding management, hospital referral and use of oxygen therapy. Funding: Funded by Pfizer Global and the Bill & Melinda Gates Foundation.

Characterization of invasive Group B Streptococcus isolates from Western Australian infants, 2004-2020.

Background. Invasive Group B Streptococcus (GBS; Streptococcus agalactiae) remains a leading cause of infant morbidity and mortality. Intrapartum antibiotic prophylaxis (IAP) has been implemented in many countries with a reduction in early-onset disease, but an effective vaccine may further reduce the disease burden. Candidate vaccines targeting capsular polysaccharides and surface proteins are now in clinical trials.Methods. Using whole-genome sequencing and phenotypic antimicrobial susceptibility testing, we characterized sterile-site GBS isolates recovered from Western Australian infants between 2004 and 2020. Characteristics were compared between three time periods: 2004-2008, 2009-2015 and 2016-2020.Results. A total of 135 isolates were identified. The proportion of serotype III (22.7 % in Period 1 to 47.9 % in Period 3, P=0.04) and clonal complex 17 (13.6-39.6 %, P=0.01) isolates increased over time. Overall coverage of vaccines currently being trialled was >95 %. No isolates were penicillin resistant (MIC>0.25 mg l-1), but 21.5 % of isolates had reduced penicillin susceptibility (MIC>0.12 mg l-1) and penicillin MIC increased significantly over time (P=0.04). Clindamycin resistance increased over time to 45.8 % in the latest period.Conclusions. Based on comprehensive characterization of invasive infant GBS in Western Australia, we found that coverage for leading capsular polysaccharide and surface protein vaccine candidates was high. The demonstrated changes in serotype and molecular type highlight the need for ongoing surveillance, particularly with regard to future GBS vaccination programmes. The reduced susceptibility to IAP agents over time should inform changes to antibiotic guidelines.

Invasive fungal disease in children with solid tumors: An Australian multicenter 10-year review.

Invasive fungal disease (IFD) occurs less frequently during treatment for solid compared to hematological malignancies in children, and risk groups are poorly defined. Retrospective national multicenter cohort data (2004-2013) were analyzed to document prevalence, clinical characteristics, and microbiology of IFD. Amongst 2067 children treated for solid malignancy, IFD prevalence was 1.9% overall and 1.4% for proven/probable IFD. Of all IFD episodes, 42.5% occurred in patients with neuroblastoma (prevalence 7.0%). Candida species comprised 54.8% of implicated pathogens in proven/probable IFD. In children with solid tumors, IFD is rare, and predominantly caused by yeasts.Routine prophylaxis may not be warranted.

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.

The effectiveness of maternal pertussis vaccination for protecting Aboriginal and Torres Strait Islander infants against infection, 2012-2017: a retrospective cohort study.

OBJECTIVES: To evaluate the effectiveness of maternal pertussis vaccination for preventing pertussis infections in Aboriginal and Torres Strait Islander infants under seven months of age. STUDY DESIGN: Retrospective cohort study; analysis of linked administrative health data. SETTING, PARTICIPANTS: Mother-infant cohort (Links2HealthierBubs) including all pregnant women who gave birth to live infants (gestational age ≥ 20 weeks, birthweight ≥ 400 g) in the Northern Territory, Queensland, and Western Australia during 1 January 2012 - 31 December 2017. MAIN OUTCOME MEASURES: Proportions of women vaccinated against pertussis during pregnancy, rates of pertussis infections among infants under seven months of age, and estimated effectiveness of maternal vaccination for protecting infants against pertussis infection, each by Indigenous status. RESULTS: Of the 19 892 Aboriginal and Torres Strait Islander women who gave birth to live infants during 2012-2017, 7398 (37.2%) received pertussis vaccine doses during their pregnancy, as had 137 034 of 259 526 non-Indigenous women (52.8%; Indigenous v non-Indigenous: adjusted odds ratio, 0.66; 95% confidence interval [CI], 0.62-0.70). The annual incidence of notified pertussis infections in non-Indigenous infants declined from 16.8 (95% CI, 9.9-29) in 2012 to 1.4 (95% CI, 0.3-8.0) cases per 10 000 births in 2017; among Aboriginal and Torres Strait Islander infants, it declined from 47.6 (95% CI, 16.2-139) to 38.6 (95% CI, 10.6-140) cases per 10 000 births. The effectiveness of maternal vaccination for protecting non-Indigenous infants under seven months of age against pertussis infection during 2014-17 was 68.2% (95% CI, 51.8-79.0%); protection of Aboriginal and Torres Strait Islander infants was not statistically significant (36.1%; 95% CI, -41.3% to 71.1%). CONCLUSIONS: During 2015-17, maternal pertussis vaccination did not protect Aboriginal and Torres Strait Islander infants in the NT, Queensland, and WA against infection. Increasing the pertussis vaccination rate among pregnant Aboriginal and Torres Strait Islander women requires culturally appropriate, innovative strategies co-designed in partnership with Indigenous organisations and communities.

Pragmatic Adaptive Trial for Respiratory Infection in Children (PATRIC) Clinical Registry protocol.

INTRODUCTION: Acute respiratory infections (ARI) are the most common cause of paediatric hospitalisation. There is an urgent need to address ongoing critical knowledge gaps in ARI management. The Pragmatic Adaptive Trial for Respiratory Infections in Children (PATRIC) Clinical Registry will evaluate current treatments and outcomes for ARI in a variety of paediatric patient groups. The registry will provide a platform and data to inform a number of PATRIC clinical trials, testing various interventions in ARI treatment and management to optimise paediatric ARI care. METHODS AND ANALYSIS: The PATRIC Clinical Registry is a single-centre, prospective observational registry recruiting from a tertiary paediatric Emergency Department in Western Australia. Through characterising demographic, clinical, treatment and outcome data, the PATRIC Clinical Registry will improve our understanding of antibiotic utilisation and ARI outcomes in children. ETHICS AND DISSEMINATION: The PATRIC Clinical Registry is conducted in accordance with the Declaration of Helsinki, and the International Council for Harmonisation (ICH) Guidelines for Good Clinical Practice (CPMP/ICH/13595) July 1996. Approval is provided by the Child and Adolescent Health Service Human Research Ethics Committee (HREC). Study results will be communicated by presentation and publication (HREC: RGS0000003078.) TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12619000903189. UTN: U1111-1231-3365.

Respiratory Syncytial Virus Reinfections in Children in Western Australia.

Respiratory syncytial virus (RSV) reinfection in children is poorly understood. We examined the incidence, characteristics, and outcomes of hospital-attended RSV reinfections in children <16 years in Western Australia between 2012 and 2022. Individuals with repeat RSV detections ≥56 days apart were identified using laboratory data. The incidence of reinfection in the first five years of life was estimated using the total birth population from 2012 to 2017. Clinical data on a subset of reinfection episodes were obtained from two metropolitan pediatric centers. A total of 466 children with hospital-attended reinfections were identified. The median interval between RSV detections was 460 days (interquartile range: 324, 812), with a reinfection rate of 95 per 100,000 individuals (95% confidence interval: 82, 109). Reinfection was most common in children who experienced their first RSV detection <6 months of age. Predisposing factors were identified in 56% of children; children with predisposing factors were older at first and second detections, were more likely to be admitted, and had a longer length of stay. This study highlights the significant burden of hospital-attended RSV reinfections in children with and without predisposing factors. Expanded surveillance with in-depth clinical data is required to further characterize the impact of RSV reinfection.

Influenza vaccination in Western Australian children: Exploring the health benefits and cost savings of increased vaccine coverage in children.

Introduction: To assess potential benefits and direct healthcare cost savings with expansion of an existing childhood influenza immunisation program, we developed a dynamic transmission model for the state of Western Australia, evaluating increasing coverage in children < 5 years and routinely immunising school-aged children. Methods: A deterministic compartmental Susceptible-Exposed-Infectious-Recovered age-stratified transmission model was developed and calibrated using laboratory-notification and hospitalisation data. Base case vaccine coverage estimates were derived from 2019 data and tested under moderate, low and high vaccine effectiveness settings. The impact of increased coverage on the burden of influenza, influenza-associated presentations and net costs were assessed using the transmission model and estimated health utilisation costs. Results: Under base case vaccine coverage and moderate vaccine effectiveness settings, 225,460 influenza cases are expected annually across all ages. Direct healthcare costs of influenza were estimated to be A$27,608,286 per annum, dominated by hospital costs. Net cost savings of >$A1.5 million dollars were observed for every 10 % increase in vaccine coverage in children < 5 years. Additional benefits were observed by including primary school age children (5-11 years) in the funded influenza vaccination program - a reduction in cases, presentations, hospitalisations and approximately $A4 million net costs savings were observed for every 10 % increase in coverage. The further addition of older children (12-17 years) resulted in only moderate additional net cost savings figures, compared with a 5-11year-old program alone. Net costs savings were predominantly derived by a reduction in influenza-associated hospitalisation in adults. Conclusions: Any increase in influenza vaccine coverage in children < 5 years, above a base case of 50 % coverage resulted in a substantive reduction in influenza cases, presentations, hospitalisations and net costs when applied to the West Australian population. However, the most impactful pediatric program, from both a disease prevention and costs perspective, would be one that increased vaccination coverage among primary-school aged children.

Maternal Pertussis Vaccination, Infant Immunization, and Risk of Pertussis.

OBJECTIVES: Following the introduction of jurisdictional maternal pertussis vaccination programs in Australia, we estimated maternal vaccine effectiveness (VE) and whether maternal pertussis vaccination modified the effectiveness of the first 3 primary doses of pertussis-containing vaccines. METHODS: We conducted a population-based cohort study of 279 418 mother-infant pairs using probabilistic linkage of administrative health records in 3 Australian jurisdictions. Infants were maternally vaccinated if their mother had a documented pertussis vaccination ≥14 days before birth. Jurisdictional immunization records were used to identify receipt of the first 3 infant doses of pertussis-containing vaccines. Infant pertussis infections were identified using notifiable disease records. VE was estimated using Cox proportional hazard models. RESULTS: Pertussis was administered during 51.7% (n = 144 429/279 418) of pregnancies, predominantly at 28-31 weeks' gestation. VE of maternal pertussis vaccination declined from 70.4% (95% confidence interval [CI], 50.5-82.3) among infants <2 months old to 43.3% (95% CI, 6.8-65.6) among infants 7-8 months old and was not significant after 8 months of age. Although we observed slightly lower VE point estimates for the third dose of infant pertussis vaccine among maternally vaccinated compared with unvaccinated infants (76.5% vs 92.9%, P = .002), we did not observe higher rates of pertussis infection (hazard ratio, 0.70; 95% CI, 0.61-3.39). CONCLUSIONS: Pertussis vaccination near 28 weeks' gestation was associated with lower risk of infection among infants through 8 months of age. Although there was some evidence of lower effectiveness of infant vaccination among maternally vaccinated infants, this did not appear to translate to greater risk of disease.

Superior immunogenicity of mRNA over adenoviral vectored COVID-19 vaccines reflects B cell dynamics independent of anti-vector immunity: Implications for future pandemic vaccines.

Both vector and mRNA vaccines were an important part of the response to the COVID-19 pandemic and may be required in future outbreaks and pandemics. The aim of this study was to validate whether immunogenicity differs for adenoviral vectored (AdV) versus mRNA vaccines against SARS-CoV-2, and to investigate how anti-vector immunity and B cell dynamics modulate immunogenicity. We enrolled SARS-CoV-2 infection-naïve health care workers who had received two doses of either AdV AZD1222 (n = 184) or mRNA BNT162b2 vaccine (n = 274) between April and October 2021. Blood was collected at least once, 10-48 days after vaccine dose 2 for antibody and B cell analyses. Median ages were 42 and 39 years, for AdV and mRNA vaccinees, respectively. Surrogate virus neutralization test (sVNT) and spike binding antibody titres were a median of 4.2 and 2.2 times lower, respectively, for AdV compared to mRNA vaccinees (p < 0.001). Median percentages of memory B cells that recognized fluorescent-tagged spike and RBD were 2.9 and 8.3 times lower, respectively for AdV compared to mRNA vaccinees. Titres of IgG reactive with human adenovirus type 5 hexon protein rose a median of 2.2-fold after AdV vaccination but were not correlated with anti-spike antibody titres. Together the results show that mRNA induced substantially more sVNT antibody than AdV vaccine, which reflected greater B cell expansion and targeting of the RBD rather than an attenuating effect of anti-vector antibodies. ClinicalTrials.gov Identifier: NCT05110911.

Respiratory syncytial virus in children: epidemiology and clinical impact post-COVID-19.

PURPOSE OF REVIEW: Respiratory syncytial virus (RSV) remains a leading cause of mortality and morbidity worldwide. RSV seasonality was disrupted by COVID-19-associated nonpharmaceutical interventions (NPIs). We review RSV seasonality, molecular epidemiology, clinical manifestations, and community awareness to inform future prevention strategies. RECENT FINDINGS: An initial reduction of RSV disease observed with NPIs, and subsequent global resurgence was associated with a collapse in genetic diversity. A lack of immunity is suggested to have contributed to the resurgence of RSV cases experienced post COVID-19. The median age of children admitted with RSV increased during the resurgence, likely secondary to the expanded cohort of RSV-immune naive children. The pandemic also played a role in increased community awareness, which can be utilized as part of a coordinated public health effort to introduce prevention strategies. Further education on signs and symptoms of RSV is still required. SUMMARY: mAbs and maternal vaccines targeting RSV have the potential to reduce paediatric morbidity, however this new era of RSV prevention will require ongoing research to facilitate community awareness and engagement, and better respiratory surveillance. Tackling the global burden of RSV will require a coordinated effort and measures to ensure access and affordability of new prevention strategies.

West Australian parents' views on vaccinating their children against COVID-19: a qualitative study.

BACKGROUND: Australian children and adolescents were among the last local cohorts offered COVID-19 vaccines. Despite promising initial uptake, coverage subsequently plateaued, requiring further efforts to improve access and build parents' recognition of the importance of COVID-19 vaccination. We sought to understand West Australian (WA) parents' willingness to vaccinate their children to inform strategies for improving uptake at the time in which they were becoming eligible. METHODS: We undertook in-depth qualitative interviews with 30 parents of children aged 5-17 years from June - December 2021. During this period, children aged 12-15 years became eligible for vaccination; children aged 5-11 years became eligible shortly thereafter. Data were thematically analysed in NVivo. RESULTS: Most parents intended on vaccinating their children once eligible. Parents sought to protect their children, to protect the community, to resume travel, and to get back to "normal". They reflected that vaccination against key infectious threats is a routine activity in childhood. Some were concerned about the vaccine, particularly mRNA vaccines, being new technology or impacting fertility. "Wait-awhiles" wanted to see what other parents would do or were delaying until they felt that there was a higher risk of COVID-19 in WA. Most parents of younger children wanted their child to be vaccinated at the general practice clinic due to familiarity and convenience. Parents were particularly eager for clear and consistent messaging about vaccination of children and adolescents, including safety, importance, scientific evidence, and personal stories. CONCLUSION: For future pandemic vaccinations pertaining to children, governments and health officials need to address parents' concerns and meet their preferences for the delivery of the vaccine program to children and adolescents.

Non-specific benefit of seasonal influenza vaccine on respiratory syncytial virus-hospitalisations in children: An instrumental variable approach using population-based data.

BACKGROUND: Seasonal influenza vaccine is effective against influenza hospitalisations, but little is known about non-specific effects of the vaccine on other respiratory pathogens with similar seasonal patterns. We aimed to assess the causal impact of seasonal influenza vaccine on laboratory-confirmed hospitalisations for respiratory syncytial virus (RSV) in children using an instrumental variable (IV) strategy. METHODS: We used probabilistically linked population-based data on childhood immunisations, births, deaths, hospitalisations, perinatal factors, and microbiology test results (2000-2013) of all Western Australian (WA) children born 2000-2012, observed longitudinally until the earliest of 7 years of age or 31 December 2013. We exploited a unique natural experiment created from the WA's state-funded preschool influenza vaccination policy commencing in 2008 and used this as an instrument for children's seasonal influenza vaccination status. We estimated a system of two simultaneous probit equations: determinants of influenza vaccine uptake, and determinants of RSV-confirmed hospitalisation. RESULTS: Influenza vaccine coverage was low prior to 2008 but increased to 36 % in children aged 6-23 months in 2009. The majority (90 %) of RSV-hospitalisations occurred in children <2 years. Receipt of influenza vaccine reduced RSV-hospitalisations, especially in those <2 years with a rate reduction of 2.27 per 1000 (95 % CI: -3.26; -1.28), and a smaller rate reduction of 0.53 per 1000 (95 % CI: -1.04; -0.02) in those 2-7 years. Over the 5-year period (2008-2013), the state-funded preschool-influenza vaccine program resulted in 1,193 fewer RSV-hospitalisations. Of these, 793 (67 %) were in young children <2 years. CONCLUSIONS: To our knowledge, this is the first analysis utilising an IV estimation strategy on a population level to assess the causal impact of seasonal influenza vaccine on risk of RSV-hospitalisations. We estimated a small protective effect that warrants further investigation.

Defining the pediatric response to SARS-CoV-2 variants.

The global population has been severely affected by the coronavirus disease 2019 (COVID-19) pandemic, however, with older age identified as a risk factor, children have been underprioritized. This article discusses the factors contributing to the less severe response observed in children following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including, differing viral entry receptor expression and immune responses. It also discusses how emerging and future variants could present a higher risk to children, including those with underlying comorbidities, in developing severe disease. Furthermore, this perspective discusses the differential inflammatory markers between critical and non-critical cases, as well as discussing the types of variants that may be more pathogenic to children. Importantly, this article highlights where more research is urgently required, in order to protect the most vulnerable of our children.

Comparative B cell and antibody responses induced by adenoviral vectored and mRNA vaccines against COVID-19.

Both vector and mRNA vaccines were an important part of the response to the COVID-19 pandemic and may be required in future outbreaks and pandemics. However, adenoviral vectored (AdV) vaccines may be less immunogenic than mRNA vaccines against SARS-CoV-2. We assessed anti-spike and anti-vector immunity among infection-naïve Health Care Workers (HCW) following two doses of AdV (AZD1222) versus mRNA (BNT162b2) vaccine. 183 AdV and 274 mRNA vaccinees enrolled between April and October 2021. Median ages were 42 and 39 years, respectively. Blood was collected at least once, 10-48 days after vaccine dose 2. Surrogate virus neutralization test (sVNT) and spike binding antibody titres were a median of 4.2 and 2.2 times lower, respectively, for AdV compared to mRNA vaccinees (p<0.001). Median percentages of memory B cells that recognized fluorescent-tagged spike and RBD were 2.9 and 8.3 times lower, respectively for AdV compared to mRNA vaccinees. Titres of IgG reactive with human Adenovirus type 5 hexon protein rose a median of 2.2-fold after AdV vaccination but were not correlated with anti-spike antibody titres. Together the results show that mRNA induced substantially more sVNT antibody than AdV vaccine due to greater B cell expansion and targeting of the RBD. Pre-existing AdV vector cross-reactive antibodies were boosted following AdV vaccination but had no detectable effect on immunogenicity.