THE ROLE OF SCHOOLS IN MENINGOCOCCAL CARRIAGE AMONG ADOLESCENTS AND YOUNG ADULTS IN SOUTH AUSTRALIA.

Neisseria meningitidis carriage peaks in adolescents. This secondary analysis of a randomized controlled trial (NCT03089086) assessing 4CMenB herd protection in South Australia ("B-Part-of-It" study) explored school attributes linked to baseline carriage in 34,489 adolescents prevaccination. Carriage was higher in students attending single-sex [adjusted odds ratio (aOR): 1.49; 95% confidence interval (CI): 1.14-1.93], boarding (aOR: 1.92; 1.13-3.27) and government schools (aOR: 1.32, 1.09-1.61).

Longitudinal study of meningococcal carriage in adolescents and young adults in South Australia 2017-2020.

BACKGROUND: This analysis investigated longitudinal changes in meningococcal carriage in adolescents in South Australia over 4 years. METHODS: Data from the "B Part of It" study, which included a state-wide cluster randomized controlled trial in secondary-school students (n = 34,489 in 2017 and 2018) and serial cross-sectional studies in school leavers aged 17-25 years (n = 4028 in 2019-2020). Individuals had oropharyngeal swabs collected annually. This study included two unique cohorts: (1) individuals enrolled in 2019, with three consecutive annual swabs taken in 2017, 2018 and 2019; and (2) individuals enrolled in 2020, with swabs taken in 2017, 2018, and 2020. Disease-associated N. meningitidis genogroups were identified using PCR and whole genome sequencing. Univariate analysis identified risk factors for recurrent carriage (≥2). RESULTS: Among school leavers, 50 (1.7%, total n = 2980) had carriage detected at successive visits. In participants with meningococcal carriage at successive visits, 38/50 (76.0%) had the same genogroup detected by porA PCR. Of those, 19 had the same MLST type and demonstrated minimal variation, indicating they most likely had sustained carriage of the same isolate (range 226 to 490 days, mean duration 352 [SD 51] days). In the 2019 school leaver cohort, 6.7% acquired carriage in their first year out of school compared to 3.3% in their final school year. Compared to single carriage detection, recurrent carriage was potentially more likely in older adolescents (16 compared to ≤15 years; OR = 1.97 (95%CI 1.0, 3.86); p = 0.048). CONCLUSION: Whilst carriage is typically transient, some adolescents/young adults may have persistent carriage and are likely to be an important group in the transmission of meningococci.

Vaccine value profile for Neisseria gonorrhoeae.

Neisseria gonorrhoeae infection (gonorrhoea) is a global public health challenge, causing substantial sexual and reproductive health consequences, such as infertility, pregnancy complications and increased acquisition or transmission of HIV. There is an urgency to controlling gonorrhoea because of increasing antimicrobial resistance to ceftriaxone, the last remaining treatment option, and the potential for gonorrhoea to become untreatable. No licensed gonococcal vaccine is available. Mounting observational evidence suggests that N. meningitidis serogroup B outer membrane vesicle-based vaccines may induce cross-protection against N. gonorrhoeae (estimated 30%-40% effectiveness using the 4CMenB vaccine). Clinical trials to determine the efficacy of the 4CMenB vaccine against N. gonorrhoeae are underway, as are Phase 1/2 studies of a new gonococcal-specific vaccine candidate. Ultimately, a gonococcal vaccine must be accessible, affordable and equitably dispensed, given that those most affected by gonorrhoea are also those who may be most disadvantaged in our societies, and most cases are in less-resourced settings. This vaccine value profile (VVP) provides a high level, holistic assessment of the current data to inform the potential public health, economic and societal value of pipeline vaccines. This was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships and multi-lateral organizations. All contributors have extensive expertise on various elements of the N. gonorrhoeae VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using published data obtained from peer-reviewed journals or reports.

National and regional differences in meningococcal vaccine recommendations for individuals at an increased risk of meningococcal disease.

INTRODUCTION: Invasive meningococcal disease (IMD) is a severe, life-threatening condition caused by infection with Neisseria meningitidis. Currently available vaccines offer protection against the five most common meningococcal disease-causing serogroups and include monovalent and quadrivalent conjugate vaccines (MenA, MenC, MenACWY vaccines) and outer membrane vesicle- and/or recombinant protein-based vaccines (MenB vaccines). AREAS COVERED: Country and regional immunization programs target populations susceptible to IMD and typically emphasize the highest-risk age groups (i.e., infants, adolescents/young adults, and the elderly); however, additional groups are also considered at an elevated risk and are the focus of the current review. Specific increased-risk groups include individuals with underlying immunocompromising medical conditions, university/college students, Indigenous people, laboratory workers, military personnel, men who have sex with men, and travelers to areas with hyperendemic IMD. This review compares established meningococcal vaccination recommendations for these vulnerable groups in Europe, the United States, Australia, New Zealand, Israel, Brazil, and Turkey. EXPERT OPINION: Recommendations should be standardized to cover all groups at increased risk of IMD.

Interventions for increasing the uptake of immunisations in healthcare workers: A systematic review.

OBJECTIVE: This systemic review aimed to evaluate the effectiveness of interventions for increasing the uptake of immunisation in healthcare workers (HCWs) compared to no or alternative interventions. METHODS: A systematic review was undertaken (until March 2022) using a search strategy established a priori to capture studies that examined the effect of interventions on vaccination levels in HCWs. We included randomised controlled trials (RCT), cluster RCTs, controlled before-after (CBA) studies and interrupted time-series (ITS) studies. We described studies descriptively and synthesized results with a fixed-effect or random-effects model meta-analysis, where appropriate. The risk of bias was assessed for each study; the quality evidence per comparison was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: We identified three RCTs, six cluster RCTs and four ITS studies. There was a diverse range of interventions; many included an educational component. Based on the evidence examined the following may be effective strategies in increasing the proportion of HCWs vaccinated: policy interventions, targeted and multicomponent strategies, tailored programs directed at management, physician delivered education with a vaccine 'champion' and individual decision analysis. Limited eligible studies restricted synthesis and interpretation of findings. No studies evaluated the effectiveness of legislation. Nor did we find studies evaluating the effectiveness of incentives on their own or studies focusing solely on improving access to vaccination. We judged all the studies as either unclear or high risk of bias. CONCLUSION: Few robust studies that evaluate interventions to increase vaccination in HCWs are available. A limitation of this systematic review is that interventions are diverse, poorly reported and few were sufficiently alike to combine in an evaluation. More research on the effects of interventions to increase vaccination in HCWs is required, this should address a variety of vaccines and not just influenza vaccination.

Randomised controlled trials of behavioural nudges delivered through text messages to increase influenza and COVID-19 vaccines among pregnant women (the EPIC study): study protocol.

BACKGROUND: Influenza and COVID-19 infections during pregnancy may have serious adverse consequences for women as well as their infants. However, uptake of influenza and COVID-19 vaccines during pregnancy remains suboptimal. This study aims to assess the effectiveness of a multi-component nudge intervention to improve influenza and COVID-19 vaccine uptake among pregnant women. METHODS: Pregnant women who receive antenatal care at five tertiary hospitals in South Australia, Western Australia and Victoria will be recruited to two separate randomised controlled trials (RCTs). Women will be eligible for the COVID-19 RCT is they have received two or less doses of a COVID-19 vaccine. Women will be eligible for the influenza RCT if they have not received the 2023 seasonal influenza vaccine. Vaccination status at all stages of the trial will be confirmed by the Australian Immunisation Register (AIR). Participants will be randomised (1:1) to standard care or intervention group (n = 1038 for each RCT). The nudge intervention in each RCT will comprise three SMS text message reminders with links to short educational videos from obstetricians, pregnant women and midwives and vaccine safety information. The primary outcome is at least one dose of a COVID-19 or influenza vaccine during pregnancy, as applicable. Logistic regression will compare the proportion vaccinated between groups. The effect of treatment will be described using odds ratio with a 95% CI. DISCUSSION: Behavioural nudges that facilitate individual choices within a complex context have been successfully used in other disciplines to stir preferred behaviour towards better health choices. If our text-based nudges prove to be successful in improving influenza and COVID-19 vaccine uptake among pregnant women, they can easily be implemented at a national level. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT05613751. Registered on November 14, 2022.

A comprehensive review of clinical and real-world safety data for the four-component serogroup B meningococcal vaccine (4CMenB).

INTRODUCTION: Neisseria meningitidis causes invasive meningococcal disease and, globally, significant morbidity, with serogroup B (MenB) being the most common cause of endemic disease and outbreaks in several regions. Extensive use of the four-component serogroup B meningococcal vaccine (4CMenB; Bexsero, GSK) and its inclusion in immunization programs in several countries have generated substantial safety data during the 9 years since its first authorization in 2013. AREAS COVERED: 4CMenB safety data from clinical trials and post-marketing surveillance studies (2011 to 2022), and spontaneously reported adverse events of medical interest from the GSK global safety database. We discuss these safety findings in relation to the benefit of 4CMenB vaccination and implications for further enhancing vaccine confidence. EXPERT OPINION: 4CMenB has been consistently well tolerated across clinical trials and post-licensure surveillance studies, despite a higher incidence of fever reported in infants than with other pediatric vaccines. Surveillance data have not identified any significant safety issues, consistent with an acceptable safety profile of 4CMenB. These findings highlight the need to balance the risk of relatively common, transient, post-immunization fever with the benefit of affording protection that reduces the risk of uncommon but potentially fatal meningococcal infection.

The four-component serogroup B meningococcal vaccine 4CMenB (Bexsero®, GSK) was licensed in 2013 and has acquired substantial safety evidence through clinical trial and real-world data. Availability of real-world and clinical 4CMenB safety evidence is important to help address vaccination hesitancy. This comprehensive review of safety data, from 9 years of 4CMenB use including recent data from the real world, shows no significant safety issues in a variety of age groups. Data show that transient fever may occur after vaccination. Invasive meningococcal disease, although rare, can be life-threatening. Abundant safety data from this review can help reassure individuals and healthcare providers on the use of 4CMenB.

Complex intervention to promote human papillomavirus (HPV) vaccine uptake in school settings: A cluster-randomized trial.

Using a cluster-randomized trial design, we aimed to evaluate a complex intervention to increase uptake of human papillomavirus (HPV) vaccination in schools. The study was undertaken in high schools in Western Australia and South Australia between 2013 and 2015 with adolescents aged 12-13 years. Interventions included education, shared decision-making, and logistical strategies. The main outcome was school vaccine uptake. Secondary outcomes included consent forms returned and mean time to vaccinate 50 students. We hypothesised that a complex intervention would increase 3-dose HPV vaccine uptake. We recruited 40 schools (21 intervention, 19 control) with 6, 967 adolescents. There was no difference between intervention and control (3-dose mean 75.7% and 78.9%, respectively). Following adjustment for baseline covariates, absolute differences in coverage in favour of the intervention group were: dose 1, 0.8% (95% CI, -1.4,3.0); dose 2, 0.2% (95% CI, -2.7, 3.1); dose 3, 0.5% (95% CI, -2.6, 3.7). The percentage of returned consent forms in intervention schools (91.4%) was higher than in control schools (difference: 6%, 95% CI, 1.4, 10.7). There was a shorter mean time to vaccinate 50 students at dose 3. The difference for dose 3 was 110 min (95% CI, 42, 177); for dose 2, 90 min (95% CI, -15, 196); and dose 1, 28 min (95% CI, -71, 127). Logs revealed the inconsistent implementation of logistical strategies. The intervention had no impact on uptake. Inadequate resourcing for logistical strategies and advisory board reluctance toward strategies with potential financial implications impacted the implementation of logistical components. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, ACTRN12614000404628, 14.04.2014. The study protocol was published in 2015 before data collection was finalised (Skinner et al., 2015). THE HPV.EDU STUDY GROUP: We would like to acknowledge the contributions to this study by members of the HPV.edu Study Group, including: Professor Annette Braunack-Mayer: Australian Centre for Health Engagement, Evidence and Values, School of Health and Society, Faculty of Arts, Social Sciences and Humanities, University of Wollongong, NSW, Australia; Dr. Joanne Collins: Women's and Children's Health Network and School of Medicine and Robinson Research Institute, University of Adelaide, SA, Australia; Associate Professor Spring Cooper: School of Public Health, City University of New York (CUNY), New York, NY, USA; Heidi Hutton: Telethon Kids Institute, University of Western Australia, WA, Australia; Jane Jones: Telethon Kids Institute, University of Western Australia, WA, Australia; Dr. Adriana Parrella: Women's and Children's Health Network and School of Medicine and Robinson Research Institute, University of Adelaide, SA, Australia; and South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia; Associate Professor David G. Regan: The Kirby Institute for Infection and Immunity in Society, Faculty of Medicine, UNSW Sydney, NSW, Australia; Professor Peter Richmond: Perth Children's Hospital, Child and Adolescent Health Service, Western Australia, Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, WA, Australia, and School of Medicine, University of Western Australia, Perth, WA, Australia; Dr. Tanya Stoney: Telethon Kids Institute, University of Western Australia, WA, Australia. Contact for the HPV.edu study group: Cristyn.Davies@sydney.edu.au or Rachel.Skinner@sydney.edu.au.

Randomized Trial of BCG Vaccine to Protect against Covid-19 in Health Care Workers.

BACKGROUND: The bacille Calmette-Guérin (BCG) vaccine has immunomodulatory "off-target" effects that have been hypothesized to protect against coronavirus disease 2019 (Covid-19). METHODS: In this international, double-blind, placebo-controlled trial, we randomly assigned health care workers to receive the BCG-Denmark vaccine or saline placebo and followed them for 12 months. Symptomatic Covid-19 and severe Covid-19, the primary outcomes, were assessed at 6 months; the primary analyses involved the modified intention-to-treat population, which was restricted to participants with a negative test for severe acute respiratory syndrome coronavirus 2 at baseline. RESULTS: A total of 3988 participants underwent randomization; recruitment ceased before the planned sample size was reached owing to the availability of Covid-19 vaccines. The modified intention-to-treat population included 84.9% of the participants who underwent randomization: 1703 in the BCG group and 1683 in the placebo group. The estimated risk of symptomatic Covid-19 by 6 months was 14.7% in the BCG group and 12.3% in the placebo group (risk difference, 2.4 percentage points; 95% confidence interval [CI], -0.7 to 5.5; P = 0.13). The risk of severe Covid-19 by 6 months was 7.6% in the BCG group and 6.5% in the placebo group (risk difference, 1.1 percentage points; 95% CI, -1.2 to 3.5; P = 0.34); the majority of participants who met the trial definition of severe Covid-19 were not hospitalized but were unable to work for at least 3 consecutive days. In supplementary and sensitivity analyses that used less conservative censoring rules, the risk differences were similar but the confidence intervals were narrower. There were five hospitalizations due to Covid-19 in each group (including one death in the placebo group). The hazard ratio for any Covid-19 episode in the BCG group as compared with the placebo group was 1.23 (95% CI, 0.96 to 1.59). No safety concerns were identified. CONCLUSIONS: Vaccination with BCG-Denmark did not result in a lower risk of Covid-19 among health care workers than placebo. (Funded by the Bill and Melinda Gates Foundation and others; BRACE ClinicalTrials.gov number, NCT04327206.).

Neonatal Group B Streptococcal Infection in Australia: A Case-control Study.

BACKGROUND: To determine maternal and neonatal risk factors for, and incidence of, neonatal early-onset group B streptococcus (EOGBS) and late-onset (LOGBS) infection in South Australia (SA) and the Northern Territory (NT). METHODS: A case-control study with 2:1 matched controls to cases. The study included tertiary hospitals in South Australia and the Northern Territory, Australia. Retrospective data were collected from a 16-year epoch (2000-2015). RESULTS: Of a total of 188 clinically suspected or confirmed cases, 139 were confirmed, of which 56.1% (n = 78) were EOGBS and 43.9% (n = 61) were LOGBS. The incidence of clinically suspected and confirmed cases of EOGBS was 0.26/1000 live births in SA and 0.73/1000 live births in the NT, and the incidence of confirmed cases was 0.19/1000 for SA and 0.36/1000 for the NT. The incidence of clinically suspected or confirmed LOGBS was 0.18/1000 live births in SA and 0.16/1000 for the NT. The majority of infants with GBS presented with sepsis, pneumonia, or meningitis. Developmental delay was the most commonly recorded long-term complication at 1 year old. Risk factors for EOGBS included maternal GBS carriage, previous fetal death, identifying as Aboriginal and/or Torres Strait Islander, and maternal fever in labor/chorioamnionitis. CONCLUSIONS: GBS remains a leading cause of neonatal morbidity and mortality. Adding previous fetal death to GBS screening guidelines would improve GBS prevention. The introduction of maternal GBS vaccination programs should be guided by country-specific disease epidemiology.

A Systematic Review and Meta-Analysis on the Real-World Effectiveness of COVID-19 Vaccines against Infection, Symptomatic and Severe COVID-19 Disease Caused by the Omicron Variant (B.1.1.529).

Real-world data on the effectiveness of COVID-19 vaccines against the Omicron variant (B.1.1.529) is limited. This systematic review aimed to investigate the real-world effectiveness and durability of protection conferred by primary course and booster vaccines against confirmed Omicron infection, and severe outcomes. We systematically searched literature up to 1 August 2022. Meta-analysis was performed with the DerSimonian-Laird random-effects model to estimate the pooled vaccine effectiveness (VE). Overall, 28 studies were included representing 11 million individuals. The pooled VE against Omicron infection was 20.4% (95%CI: 12.1-28.7%) and 23.4% (95%CI: 13.5-33.3%) against symptomatic infection with variation based on vaccine type and age groups. VE sharply declined from 28.1% (95%CI: 19.1-37.1%) at three months to 3.9% (95%CI: -24.8-32.7%) at six months. Similar trends were observed for symptomatic Omicron infection. A booster dose restored protection against Omicron infection up to 51.1% (95%CI: 43.8-58.3%) and 57.3% (95%CI: 54.0-60.5%) against symptomatic infection within three months; however, this waned to 32.8% (95%CI: 16.8-48.7%) within six months. VE against severe Omicron infection following the primary course was 63.6% (95%CI: 57.5-69.7%) at three months, decreased to 49% (95%CI: 35.7-63.4%) within six months, and increased to 86% after the first or second booster dose.

Short Message Service Reminder Nudge for Parents and Influenza Vaccination Uptake in Children and Adolescents With Special Risk Medical Conditions: The Flutext-4U Randomized Clinical Trial.

Importance: Children with chronic medical conditions are at increased risk of severe influenza. Uptake of influenza vaccination in children and adolescents with these identified special risk medical conditions (SRMCs) is suboptimal. Objective: To assess the effectiveness of Flutext-4U, a parent short message service (SMS) reminder nudge intervention, in increasing influenza immunization in children and adolescents with SRMCs. Design, Setting, and Participants: This randomized clinical trial was conducted at a tertiary pediatric hospital in Adelaide, South Australia, from April 15 to September 30, 2021. Children and adolescents aged 6 months to younger than 18 years with SRMCs and a subspecialist outpatient appointment over a 5-month period during the Australian seasonal influenza vaccination season (April-August 2021) were eligible to participate. Follow-up was until September 30, 2021. Interventions: Participants were randomly assigned (1:1 ratio) to control: clinician nudges (hospital vaccine availability, ease of access, and recommendation from hospital subspecialists) or SMS intervention (control conditions plus an additional SMS reminder nudge to parents), with randomization stratified by age group (<5 years, 5-14 years, or >14 to <18 years). Main Outcomes and Measures: The primary outcome was influenza vaccination, as confirmed by the Australian Immunisation Register. Results: A total of 600 participants (intervention group: 298 [49.7%]; mean [SD] age, 11.5 [4.6] years; 162 female participants [54.4%]; control group: 302 [50.3%]; mean [SD] age, 11.4 [4.7] years; 155 female participants [51.3%]) were included. Influenza vaccination was 38.6% (113 of 293) in the SMS intervention group compared with 26.2% (79 of 302) in the control group (adjusted odds ratio [aOR], 1.79; 95% CI, 1.27-2.55; P = .001). Time to vaccine receipt was significantly lower among SMS participants (adjusted hazard ratio, 1.67; 95% CI, 1.25-2.22; P < .001). For participants randomly assigned by June 15, a significantly greater proportion receiving the SMS intervention were vaccinated during the optimal delivery period April to June 30 (SMS group: 40.0% [76 of 190] vs 25.4% [50 of 197]; aOR, 1.97; 95% CI, 1.28-3.06; P = .002). Conclusions and Relevance: Results of this randomized clinical trial suggest that an additional SMS reminder nudge for parents delivered in the tertiary care hospital setting to children and adolescents with SMRCs resulted in higher influenza vaccine uptake compared with clinician nudges alone. Trial Registration: ANZCTR Identifier: ACTRN12621000463875.

Real world impact of 13vPCV in preventing invasive pneumococcal pneumonia in Australian children: A national study.

BACKGROUND: We aimed to assess the direct protective effect of 13 valent pneumococcal conjugate vaccine (13vPCV) against invasive pneumococcal pneumonia (IPP; including pneumonia and empyema) in children using a nation-wide case-control study across 11 paediatric tertiary hospitals in Australia. METHODS: Children < 18 years old admitted with pneumonia were eligible for enrolment. IPP was defined as Streptococcus pneumoniae (SP) cultured or detected by polymerase chain reaction (PCR) from blood or pleural fluid. Causative SP serotype (ST) was determined from blood or pleural fluid SP isolates by molecular methods in PCR positive specimens or else inferred from nasopharyngeal isolates. For each IPP case, 20 population controls matched by age and socio-economic status were sampled from the Australian Immunisation Register. Conditional logistic regression was used to estimate the adjusted odds ratio (aOR) of being fully vaccinated with 13vPCV (≥3 doses versus < 3 doses) among IPP cases compared to controls, adjusted for sex and Indigenous status. RESULTS: From February 2015 to September 2018, we enrolled 1,168 children with pneumonia; 779 were 13vPCV-eligible and were individually matched to 15,580 controls. SP was confirmed in 195 IPP cases, 181 of whom had empyema. ST3 and ST19A were identified in 52% (102/195) and 11% (21/195) of IPP cases respectively. The aOR of being fully vaccinated with 13vPCV was 0.8 (95% CI 0.6-1.0) among IPP cases compared to matched controls. CONCLUSION: We failed to identify a strong direct protective effect of 13vPCV against IPP among Australian children, where disease was largely driven by ST3.

Safety and immunogenicity of a primary series and booster dose of the meningococcal serogroup B-factor H binding protein vaccine (MenB-FHbp) in healthy children aged 1-9 years: two phase 2 randomised, controlled, observer-blinded studies.

BACKGROUND: The meningococcal serogroup B-factor H binding protein vaccine (MenB-FHbp) is licensed for use in children aged 10 years or older for protection against invasive serogroup B meningococcal disease. Because young children are at increased risk of invasive meningococcal disease, MenB-FHbp clinical data in this population are needed. METHODS: We conducted two phase 2 randomised, controlled, observer-blinded studies including healthy toddlers (age 12-23 months) across 26 Australian, Czech, Finnish, and Polish centres, and older children (age 2-9 years) across 14 Finnish and Polish centres. Exclusion criteria included previous vaccinations against serogroup B meningococcus or hepatitis A virus (HAV), and chronic antibiotic use. Toddlers were randomly allocated (2:1) via an interactive response technology system to receive either 60 µg or 120 µg MenB-FHbp or HAV vaccine and saline (control). Older children were randomly allocated (3:1) to receive 120 µg MenB-FHbp or control, with stratification by age group (2-3 years and 4-9 years). All vaccinations were administered as three doses (0, 2, and 6 months, with only saline given at 2 months in the control group). Toddlers who received 120 µg MenB-FHbp could receive a 120 µg booster dose 24 months after the end of the primary series. The percentages of participants with serum bactericidal activity using human complement (hSBA) titres at or above the lower limit of quantification (LLOQ; all greater than the 1:4 correlate of protection) against four test strains of serogroup B meningococcus 1 month after the third dose (primary immunogenicity endpoint) were measured in the evaluable immunogenicity populations (participants who received the vaccine as randomised, had available and determinate hSBA results, and had no major protocol violations). Not all participants were tested against all strains because of serum sample volume constraints. The frequencies of reactogenicity and adverse events after each dose were recorded in the safety population (all participants who received at least one dose and had safety data available). These studies are registered with ClinicalTrials.gov (NCT02534935 and NCT02531698) and are completed. FINDINGS: Between Aug 31, 2015, and Aug 22, 2016, for the toddler study and between Aug 27, 2015, and March 7, 2016, for the older children study, we enrolled and randomly allocated 396 toddlers (60 µg MenB-FHbp group n=44; 120 µg MenB-FHbp group n=220; control group n=132) and 400 older children (120 µg MenB-FHbp group n=294; control group n=106). 1 month after the third dose, the proportions of participants with hSBA titres at or above the LLOQ ranged across test strains from 85·0% (95% CI 62·1-96·8; 17 of 20 participants) to 100·0% (82·4-100·0; 19 of 19) in toddlers receiving 60 µg MenB-FHbp, and from 71·6% (61·4-80·4; 68 of 95) to 100·0% (96·2-100·0; 95 of 95) in toddlers receiving 120 µg MenB-FHbp, and from 79·1% (71·2-85·6; 106 of 134) to 100·0% (97·4-100·0; 139 of 139) in children aged 2-9 years receiving 120 µg MenB-FHbp. hSBA titres peaked at 1 month after the third primary dose of MenB-FHbp and then declined over time. 24 months after the third dose in the toddler study, the proportions with hSBA titres at or above the LLOQ ranged from 0·0% (0·0-17·6; 0 of 19 participants) to 41·2% (18·4-67·1; seven of 17) in those who received 60 µg MenB-FHbp and from 3·7% (0·8-10·4; three of 81) to 22·8% (14·1-33·6; 18 of 79) in those who received 120 µg MenB-FHbp. 1 month after the booster dose in toddlers, the proportions with hSBA titres at or above the LLOQ were higher than at 1 month after the primary series. MenB-FHbp reactogenicity was mostly transient and of mild to moderate severity. Adverse event frequency was similar between the MenB-FHbp and control groups and less frequent following MenB-FHbp booster than following primary doses. Two participants from the toddler study (both from the 120 µg MenB-FHbp group) and four from the older children study (three from the 120 µg MenB-FHbp group and one from the control group) were withdrawn from the study because of adverse events. INTERPRETATION: MenB-FHbp was well tolerated and induced protective immune responses in a high proportion of participants. These findings support a favourable MenB-FHbp immunogenicity and reactogenicity profile in young children, a population at increased risk of adverse invasive meningococcal disease outcomes. FUNDING: Pfizer.

Impact of COVID-19 Containment Strategies and Meningococcal Conjugate ACWY Vaccination on Meningococcal Carriage in Adolescents.

OBJECTIVES: To examine if COVID-19 containment strategies were associated with reduced pharyngeal carriage of meningococci in adolescents. Also, to observe if carriage prevalence of meningococcal A, C, W and Y differed in meningococcal conjugate ACWY vaccinated and unvaccinated adolescents. DESIGN: Repeat cross-sectional study of pharyngeal carriage. SETTING: In 2020, recruitment commenced from February to March (pre-COVID-19) and recommenced from August to September (during COVID-19 measures) in South Australia. PARTICIPANTS: Eligible participants were between 17 and 25 years of age and completed secondary school in South Australia in 2019. RESULTS: A total of 1338 school leavers were enrolled in 2020, with a mean age of 18.6 years (standard deviation 0.6). Pharyngeal carriage of disease-associated meningococci was higher during the COVID-19 period compared with the pre-COVID-19 period (41/600 [6.83%] vs. 27/738 [3.66%]; adjusted odds ratio [aOR], 2.03; 95% CI: 1.22-3.39; P = 0.01). Nongroupable carriage decreased during COVID period (1.67% vs. 3.79%; aOR, 0.45; 95% CI: 0.22-0.95). Pharyngeal carriage of groups A, C, W and Y was similar among school leavers vaccinated with meningococcal conjugate ACWY (7/257 [2.72%]) compared with those unvaccinated (29/1081 [2.68%]; aOR, 0.86; 95% CI: 0.37-2.02; P = 0.73). Clonal complex 41/44 predominated in both periods. CONCLUSIONS: Meningococcal carriage prevalence was not impacted by public health strategies to reduce severe acute respiratory syndrome coronavirus 2 transmission and is unlikely to be the mechanism for lower meningococcal disease incidence. As international travel resumes and influenza recirculates, clinicians must remain vigilant for signs and symptoms of meningococcal disease. Vaccinating people at the highest risk of invasive meningococcal disease remains crucial despite containment strategies.

A Prospective Study Investigating the Impact of Obesity on the Immune Response to the Quadrivalent Influenza Vaccine in Children and Adolescents.

Obesity can increase the severity of influenza infection. Data are limited regarding immune responses to influenza vaccination in obese children. We aimed to investigate the impact of obesity on quadrivalent influenza vaccine responses in children. Children with obesity (body mass index (BMI) ≥ 95th percentile for age and gender) and children without obesity (BMI < 95th percentile) were enrolled in the study. Blood samples were collected before, 1, and 6 months after influenza vaccination, to measure antibody responses by haemagglutination inhibition (HI) assay. Vaccine immunogenicity outcomes were compared between children with and without obesity. Forty-four children (mean age 13.3 ± 2.1 years, 18 males and 14 with obesity) completed the 6-month study. More than 90% of the participants with and without obesity had seroprotective antibody titres (HI ≥ 40) at both 1 and 6 months following vaccination for each of the four influenza strains (A/H3N2, A/H1N1, B/(Victoria) and B/(Yamagata)). Influenza-specific geometric mean titres at baseline, 1, and 6 months post-vaccination were similar between children with and without obesity for all influenza vaccine strains. Children with and without obesity have robust, sustained antibody responses over 6 months to the quadrivalent influenza vaccine.

Surveillance for severe influenza and COVID-19 in patients admitted to sentinel Australian hospitals in 2020: the Influenza Complications Alert Network (FluCAN).

Introduction: Influenza is a common cause of acute respiratory infection, and is a major cause of morbidity and mortality. Coronavirus disease 2019 (COVID-19) is an acute respiratory infection that emerged as a pandemic worldwide before the start of the 2020 Australian influenza season. This report summarises the epidemiology of hospitalisations with laboratory-confirmed influenza and COVID-19 during the 2020 influenza season in a sentinel surveillance system. Methods: The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at sites in all jurisdictions in Australia. Influenza and COVID-19 cases were defined as patients hospitalised at sentinel hospitals and confirmed by nucleic acid detection. Results: There were 448 patients with COVID-19 admitted between 16 March and 31 December 2020, and only 20 patients with influenza admitted between 1 April and 30 November 2020, to one of 22 FluCAN hospitals. Of the COVID-19 cases, 173 (39%) were > 65 years of age, 36 (8%) were children (< 16 years), 6 (1%) were Aboriginal and Torres Strait Islander peoples, 4 (1%) were pregnant and 289 (65%) had chronic comorbidities. COVID-19 hospital admissions peaked between weeks 13 and 15 (first wave) nationally, and again between weeks 31 and 35 (Victoria), with most admissions represented by those above 40 years of age. Discussion: There was an unusually low number of hospital admissions with laboratory-confirmed influenza in this season, compared to recent seasons. This is likely to be due to effective public health interventions and international border closures as a result of a rise in COVID-19 respiratory infections and associated hospitalisations.

Influenza epidemiology in patients admitted to sentinel Australian hospitals in 2019: the Influenza Complications Alert Network (FluCAN).

Influenza is a common cause of acute respiratory infection, and is a major cause of morbidity and mortality. This report summarises the epidemiology of hospitalisations with laboratory-confirmed influenza during the 2019 influenza season. The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at sites in all jurisdictions in Australia. Cases were defined as patients hospitalised at any of the 17 sentinel hospitals with influenza confirmed by nucleic acid detection. Data were also collected on a frequency matched control group of influenza-negative patients admitted with acute respiratory infection. During the period 1 April to 31 October 2019 (the 2019 influenza season), there were 4,154 patients admitted with confirmed influenza to one of 17 FluCAN sentinel hospitals. Of these, 44% were elderly (≥ 65 years), 21% were children (< 16 years), 7.7% were Aboriginal and Torres Strait Islander peoples, 1.7% were pregnant and 73% had chronic comorbidities. Most admissions were due to influenza A infection (85%). Estimated vaccine coverage was 75% in the elderly, 49% in non-elderly adults with medical comorbidities, and 27% in young children (< 5 years). The estimated vaccine effectiveness in the target adult population was 42% (95% confidence interval [95% CI]: 36%, 49%). There were a larger number of hospital admissions detected with confirmed influenza in this national observational surveillance system in 2019 than in 2018.