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.

Embedding of exogenous B cell epitopes on the surface of UreB structure generates a broadly reactive antibody response against Helicobacter pylori.

Since Helicobacter pylori (H. pylori) resistance to antibiotic regimens has increased, vaccination is becoming an increasingly important alternative therapy to control H. pylori infection. UreB, FlaA, AlpB, SabA, and HpaA proteins of H. pylori were previously proved to be used as candidate vaccine antigens. Here, we developed an engineered antigen based on a recombinant chimeric protein containing a structural scaffold from UreB and B cell epitopes from FlaA, AlpB, SabA, and HpaA. The multi-epitope chimeric antigen, named MECU, could generate a broadly reactive antibody response including antigen-specific antibodies and neutralising antibodies against H. pylori urease and adhesins. Moreover, therapeutic immunisation with MECU could reduce H. pylori colonisation in the stomach and protect the stomach in BALB/c mice. This study not only provides promising immunotherapy to control H. pylori infection but also offers a reference for antigen engineering against other pathogens.

Heterologous versus homologous COVID-19 booster vaccinations for adults: systematic review with meta-analysis and trial sequential analysis of randomised clinical trials.

BACKGROUND: To combat coronavirus disease 2019 (COVID-19), booster vaccination strategies are important. However, the optimal administration of booster vaccine platforms remains unclear. Herein, we aimed to assess the benefits and harms of three or four heterologous versus homologous booster regimens. METHODS: From November 3 2022 to December 21, 2023, we searched five databases for randomised clinical trials (RCT). Reviewers screened, extracted data, and assessed bias risks independently with the Cochrane risk-of-bias 2 tool. We conducted meta-analyses and trial sequential analyses (TSA) on our primary (all-cause mortality; laboratory confirmed symptomatic and severe COVID-19; serious adverse events [SAE]) and secondary outcomes (quality of life [QoL]; adverse events [AE] considered non-serious). We assessed the evidence with the GRADE approach. Subgroup analyses were stratified for trials before and after 2023, three or four boosters, immunocompromised status, follow-up, risk of bias, heterologous booster vaccine platforms, and valency of booster. RESULTS: We included 29 RCTs with 43 comparisons (12,538 participants). Heterologous booster regimens may not reduce the relative risk (RR) of all-cause mortality (11 trials; RR 0.86; 95% CI 0.33 to 2.26; I2 0%; very low certainty evidence); laboratory-confirmed symptomatic COVID-19 (14 trials; RR 0.95; 95% CI 0.72 to 1.25; I2 0%; very low certainty); or severe COVID-19 (10 trials; RR 0.51; 95% CI 0.20 to 1.33; I2 0%; very low certainty). For safety outcomes, heterologous booster regimens may have no effect on SAE (27 trials; RR 1.15; 95% CI 0.68 to 1.95; I2 0%; very low certainty) but may raise AE considered non-serious (20 trials; RR 1.19; 95% CI 1.08 to 1.32; I2 64.4%; very low certainty). No data on QoL was available. Our TSAs showed that the cumulative Z curves did not reach futility for any outcome. CONCLUSIONS: With our current sample sizes, we were not able to infer differences of effects for any outcomes, but heterologous booster regimens seem to cause more non-serious AE. Furthermore, more robust data are instrumental to update this review.

Driving delivery and uptake of catch-up vaccination among adolescent and adult migrants in UK general practice: a mixed methods pilot study.

BACKGROUND: Migrants in the UK and Europe face vulnerability to vaccine-preventable diseases (VPDs) due to missed childhood vaccines and doses and marginalisation from health systems. Ensuring migrants receive catch-up vaccinations, including MMR, Td/IPV, MenACWY, and HPV, is essential to align them with UK and European vaccination schedules and ultimately reduce morbidity and mortality. However, recent evidence highlights poor awareness and implementation of catch-up vaccination guidelines by UK primary care staff, requiring novel approaches to strengthen the primary care pathway. METHODS: The 'Vacc on Track' study (May 2021-September 2022) aimed to measure under-vaccination rates among migrants in UK primary care and establish new referral pathways for catch-up vaccination. Participants included migrants aged 16 or older, born outside of Western Europe, North America, Australia, or New Zealand, in two London boroughs. Quantitative data on vaccination history, referral, uptake, and sociodemographic factors were collected, with practice nurses prompted to deliver catch-up vaccinations following UK guidelines. Focus group discussions and in-depth interviews with staff and migrants explored views on delivering catch-up vaccination, including barriers, facilitators, and opportunities. Data were analysed using STATA12 and NVivo 12. RESULTS: Results from 57 migrants presenting to study sites from 18 countries (mean age 41 [SD 7.2] years; 62% female; mean 11.3 [SD 9.1] years in UK) over a minimum of 6 months of follow-up revealed significant catch-up vaccination needs, particularly for MMR (49 [86%] required catch-up vaccination) and Td/IPV (50 [88%]). Fifty-three (93%) participants were referred for any catch-up vaccination, but completion of courses was low (6 [12%] for Td/IPV and 33 [64%] for MMR), suggesting individual and systemic barriers. Qualitative in-depth interviews (n = 39) with adult migrants highlighted the lack of systems currently in place in the UK to offer catch-up vaccination to migrants on arrival and the need for health-care provider skills and knowledge of catch-up vaccination to be improved. Focus group discussions and interviews with practice staff (n = 32) identified limited appointment/follow-up time, staff knowledge gaps, inadequate engagement routes, and low incentivisation as challenges that will need to be addressed. However, they underscored the potential of staff champions, trust-building mechanisms, and community-based approaches to strengthen catch-up vaccination uptake among migrants. CONCLUSIONS: Given the significant catch-up vaccination needs of migrants in our sample, and the current barriers to driving uptake identified, our findings suggest it will be important to explore this public health issue further, potentially through a larger study or trial. Strengthening existing pathways, staff capacity and knowledge in primary care, alongside implementing new strategies centred on cultural competence and building trust with migrant communities will be important focus areas.

Efficacy and safety of tixagevimab/cilgavimab as passive immunisation against COVID-19 infections in patients with hematological malignancies.

Monoclonal antibodies, as tixagevimab/cilgavimab, have been introduced as prophylaxis against COVID-19 infections in high-risk populations. However, data on efficacy are limited. This study investigates efficacy and tolerability of tixagevimab/cilgavimab in hematological patients under real-life conditions. Tixagevimab/cilgavimab was administered to 155 hematological patients (March-August 2022) at two Austrian centres. S/RBD-antibody assessments were performed before (T0), four weeks (T1), and six months (T2) after application. Side effects, the occurrence of COVID-19 infections, and the course of S/RBD-antibody titres were analysed retrospectively in relation to clinical variables. 155 hematological patients, who refused tixagevimab/cilgavimab, were included as a control group to compare the frequency of COVID-19 infections. Of all immunised patients (52.3% males; 91% triple vaccinated), 25.8% had a COVID-19 breakthrough infection (76% mild) compared to 43.9% in the control group. Patients with chronic lymphocytic leukaemia (CLL)/lymphoma were at highest risk of a COVID-19 infection (OR = 2.21; 95% CI 1.05-4.65; p = 0.037). After immunisation, a steep increase in median antibody levels (1193.4BAU/ml, IQR 0-2318.94) was observed in 67.8%, followed by a rapid decrease between T1 and T2 (465.95BAU/ml, IQR 0-1900.65.3) with the greatest declines in CLL/lymphoma (848.7BAU/ml, IQR 0-1949.6, p = 0.026). Side-effects occurred in 21.2% (CTCAE I/II). These real-world data indicate that S/RBD antibodies respond rapidly after passive immunisation in all hematological patients without safety concerns. Given the rapid decline in S/RBD antibodies, early booster immunisations should be considered for future scenarios in this vulnerable group.

Anti-amyloid antibody treatments for Alzheimer's disease.

Our aim is to review the most recent evidence on novel antibody therapies for Alzheimer's disease directed against amyloid-ß. This is a joint statement of the European Association of Neurology and the European Psychiatric Association. After numerous unsuccessful endeavors to create a disease-modifying therapy for Alzheimer's disease, substantial and consistent evidence supporting the clinical effectiveness of monoclonal antibodies aimed at amyloid-ß is finally emerging. The latest trials not only achieved their primary objective of slowing the progression of the disease over several months but also demonstrated positive secondary clinical outcomes and a decrease in amyloid-ß levels as observed through positron emission tomography scans. Taken as a whole, these findings mark a significant breakthrough by substantiating that reducing amyloid-ß yields tangible clinical benefits, beyond mere changes in biomarkers. Concurrently, the regular utilization of the new generation of drugs will determine whether statistical efficacy translates into clinically meaningful improvements. This may well signify the dawning of a new era in the development of drugs for Alzheimer's disease.

Effect of prior immunisation with smallpox vaccine for protection against human Mpox: A systematic review.

Monkeypox is an emerging threat to humans since a new outbreak in May 2022. It is hypothesised that increasing the immunologically naive population after the cessation of the smallpox vaccination campaign in the 1980s is one of the leading causes of it. A literature search was conducted using different electronic databases including MEDLINE (through PubMed), SCOPUS, Web of Science, Cochrane library, and EMBASE for relevant studies. After duplication removal, abstract and title screening, and full-text screening were done, the data were extracted, tabulated, and analysed. The risk of bias was assessed following the Risk of Bias Assessment tool for Non-randomised Studies. We found a total of 1068 relevant articles and finally, we included 6 articles including 2083 participants. The studies suggested that smallpox is 80.7% efficacious to prevent human monkeypox and the immunity provided by prior smallpox vaccination is long-lasting. Moreover, the smallpox vaccination decreases the risk of human monkeypox by 5.2-folds. Two cross-sectional studies based on the Democratic Republic of the Congo (DRC) including a total of around 1800 monkeypox cases found that unvaccinated participants had 2.73 and 9.64-fold increased risk of monkeypox compared to the vaccinated participants. Other studies in USA and Spain also demonstrated that unvaccinated people were more prone to develop monkeypox than vaccinated people. Furthermore, monkeypox incidence has increased by 20 folds, 30 years after the cessation of the smallpox vaccination campaign in DRC. Evidence-based preventive and therapeutic agents are still not available for human monkeypox. Further study should be done to explore the role of the smallpox vaccine in preventing human monkeypox.

Global polio eradication; can we replicate the smallpox success story?

Although the Global Polio Eradication Initiative has been largely successful in elimination of polio from various parts of the world, sporadic local outbreaks in non-endemic areas continue to pose a threat to global polio eradication efforts. In the two endemic countries, Pakistan and Afghanistan, a staggering 176 cases of wild poliovirus 1 (WPV1) were reported in 2019. In 2020 alone, 959 cases of Circulating Vaccine Derived Poliovirus 2 were reported globally from 27 countries. After staying polio-free for years, cases of WPV were detected in Malawi and Mozambique in 2022. The roots of the reported strains matched with the WPV strain from Pakistan. The emergence of WPV cases in Malawi and Mozambique underscores the fact that WPV still has the chance to spread beyond the Afghanistan-Pakistan region and sustained efforts are required for its complete eradication. In the case of smallpox, surveillance-containment was the key to eradication as many countries had already eradicated smallpox and the bigger concern was to track and contain any new cases emerging. Smallpox eradication followed a comprehensive plan which included elements like quality control and standardisation of vaccination protocols. Governments all over the world should prioritise immunisation drives, surveillance, and awareness campaigns to achieve the dream of a polio-free world.

Safety of varicella vaccination strategies: An overview of reviews.

The safety of new vaccines under development as well as existing vaccines is a key priority for national and international public health agencies. A number of countries have implemented universal childhood varicella vaccination programmes over the past 30 years. However, strategies differ in terms of the number of doses, type of vaccine(s) recommended, age at vaccination and interval between doses for a two-dose schedule. An overview of reviews was undertaken to assess the existing systematic review evidence of the safety of varicella vaccination strategies. The review was restricted to immunocompetent children aged 9 months to 6 years inclusive. A comprehensive search of databases, registries and grey literature was conducted up to 2 February 2022. Two reviewers independently screened, extracted data and assessed the methodological quality of included reviews. Overlap of included reviews was also assessed. A total of 17 reviews, incorporating both the monovalent varicella only and quadrivalent measles-mumps-rubella-varicella (MMRV) vaccines were included in the overview; six assessed the safety of one-dose strategies, four assessed the safety of two-dose strategies and 14 reviews did not specify the dosing strategy. The evidence suggests that mild local and systemic reactions are relatively common with varicella vaccination. Febrile seizures are also possible adverse effects of both the monovalent and quadrivalent MMRV vaccine, but serious adverse reactions are rare. While most reviews contained methodological flaws, and analysis by vaccine type and dosing strategy was restricted due to lack of detail in reporting of the reviews, there was clear and consistent evidence from a substantial evidence base, comprising 34 randomised controlled trials and 62 other primary studies/reviews, that varicella vaccination is safe.

Clinical efficacy and effectiveness of alternative varicella vaccination strategies: An overview of reviews.

A number of countries have implemented universal childhood varicella vaccination programmes over the past 30 years. However, strategies differ in terms of dosing schedule (one- or two-dose), type of vaccine(s) recommended (monovalent, quadrivalent measles-mumps-rubella-varicella, or both), age at vaccination, and dosing interval for a two-dose schedule. An overview of reviews was undertaken to assess the existing systematic review evidence of the clinical efficacy/effectiveness of alternative varicella vaccination strategies. A comprehensive search of databases, registries and grey literature was conducted up to 2 February 2022. Two reviewers independently screened, extracted data and assessed the methodological quality of included reviews. A total of 20 reviews were included in the overview; 17 assessed the efficacy/effectiveness of one-dose strategies and 10 assessed the efficacy/effectiveness of two-dose strategies. Although the quality of most reviews was deemed 'critically low', there was clear and consistent evidence that vaccination is very effective at reducing varicella. While the analysis was restricted due to lack of detail in reporting of the reviews, the evidence suggests that two-dose strategies are more efficacious/effective than one-dose strategies in preventing varicella of any severity, but that both strategies have similar high efficacy/effectiveness in preventing moderate or severe varicella. Based on this evidence in this overview of reviews, a key consideration for policymakers on the possible introduction of a childhood varicella vaccination programme and the choice between a one- or two-dose strategy, will be whether the objective of a programme is to prevent varicella of any severity or to prevent moderate to severe varicella.

Reduced risk for Omicron SARS-CoV-2 infection observed in older adults with hybrid immunity.

BACKGROUND: Hybrid SARS-CoV-2 immunity may provide longer duration protection against severe SARS-CoV-2 infection and hospitalisation than purely vaccine-derived immunity. Older adults represent a high-risk group for severe disease, yet available data is skewed towards younger adults. METHODS: A prospective longitudinal study at a large London long-term care facility (LTCF) was conducted from March 2020 to April 2022 to assess the effect of hybrid versus vaccine-only immunity on SARS-CoV-2 infection in older adults during Omicron variant dominance. Hybrid immunity was assessed by a combination of SARS-CoV-2 polymerase chain reaction testing weekly (asymptomatic screening) and as required (symptomatic testing), as well as serial SARS-CoV-2 serology. RESULTS: 280 participants (median age 82 yrs, IQR 76-88 yrs; 95.4% male) were followed up. 168/280 (60%) had evidence of hybrid immunity prior to the Omicron variant wave. Participants with hybrid immunity had substantially lower odds of acquiring COVID-19 infection during the Omicron wave compared to those with vaccine-only immunity (unadjusted odds ratio 0.26, 95% CI 0.14-0.47, chi-squared P < .0001). Participants with hybrid immunity had an odds ratio of 0.40 (0.19-0.79) for asymptomatic infection and 0.15 (0.06-0.34) for symptomatic infection (Likelihood ratio test, P < .0001). DISCUSSION: Our data highlight potential opportunities to target ongoing booster vaccination campaigns for those most at risk of severe infection. Reporting of data in older adults will be of particular value to examine the effect of hybrid immunity as new variants continue to emerge and vaccination strategies evolve.

Vaccination against COVID-19 - risks and benefits in children.

Countries in Europe and around the world have taken varying approaches to their policies on COVID-19 vaccination for children. The low risk of severe illness from COVID-19 means that even small risks from vaccination warrant careful consideration. Vaccination appears to result in a decreased risk of severe illness including the paediatric multi-system inflammatory syndrome known to be associated with COVID-19. These risks have already decreased significantly with the emergence of the Omicron variant and its subvariants, and due to widespread population immunity through previous infection. There is a relatively high risk of myocarditis following second doses of mRNA vaccines in adolescent males, although the general course of this condition appears mild.   Conclusion: COVID-19 vaccination only provides a transient reduction in transmission. Currently, insufficient evidence exists to determine the impact of vaccination on post-acute COVID syndromes in children, which are uncommon. What is Known: • Vaccines against COVID-19 have significantly reduced morbidity and mortality around the world. • Whilst countries have universally recommended vaccines for adults and continue to recommend them for vulnerable populations, there has been more variability in recommendations for children. What is New: • In the setting of near universal existing immunity from infection, the majority of the initial benefit in protecting against severe illness has been eroded. • The risks of myocarditis following mRNA vaccination for children is low, but an important consideration given the modest benefits.

Immunisation coverage and factors associated with incomplete immunisation in children under two during the COVID-19 pandemic in Sierra Leone.

BACKGROUND: Routine childhood immunisation is one of the most important life-saving public health interventions. However, many children still have inadequate access to these vaccines and millions remain (partially) unvaccinated globally. As the COVID-19 pandemic disrupted health systems worldwide, its effects on immunisation have become apparent. This study aimed to estimate routine immunisation coverage among children under two in Sierra Leone and to identify factors associated with incomplete immunisation during the COVID-19 pandemic. METHODS: A cross-sectional household survey was conducted in three districts in Sierra Leone: Bombali, Tonkolili and Port Loko. A three-stage cluster sampling method was followed to enrol children aged 10-23 months. Information regarding immunisation status was based on vaccination cards or caretaker's recall. Using WHO's definition, a fully immunised child received one BCG dose, three oral polio vaccine doses, three pentavalent vaccine doses and one measles-containing vaccine dose. Following the national schedule, full immunisation status can be achieved at 9 months of age. Data were weighted to reflect the survey's sampling design. Associations between incomplete immunisation and sociodemographic characteristics were assessed through multivariable logistic regression. RESULTS: A total of 720 children were enrolled between November and December 2021. Full vaccination coverage was estimated at 65.8% (95% CI 60.3%-71.0%). Coverage estimates were highest for vaccines administered at birth and decreased with doses administered subsequently. Adjusting for age, the lowest estimated coverage was 40.7% (95% CI 34.5%-47.2%) for the second dose of the measles-containing vaccine. Factors found to be associated with incomplete immunisation status were: living in Port Loko district (aOR = 3.47, 95% CI = 2.00-6.06; p-value < 0.001), the interviewed caretaker being Muslim (aOR = 1.94, 95% CI = 1.25-3.02; p-value = 0.015) and the interviewed caretaker being male (aOR = 1.93, 95% CI = 1.03-3.59, p-value = 0.039). CONCLUSION: Though full immunisation coverage at district level improved compared with pre-pandemic district estimates from 2019, around one in three surveyed children had missed at least one basic routine vaccination and over half of eligible children had not received the recommended two doses of a measles-containing vaccine. These findings highlight the need to strengthen health systems to improve vaccination uptake in Sierra Leone, and to further explore barriers that may jeopardise equitable access to these life-saving interventions.

Adaptation and application of the Parent Attitudes About Childhood Vaccines survey tool in the Vietnamese language: a cross-sectional study.

BACKGROUND: Parental vaccine hesitancy could lead to outbreaks of vaccine-preventable diseases. Although parental vaccine hesitancy exists in the Vietnamese community, no research has directly investigated this social phenomenon in Vietnam. Among the validated measures, the 15-item Parent Attitudes About Childhood Vaccines survey tool (PACV) was reliable for predicting vaccine-hesitant parents. However, the PACV was not available in Vietnamese. This study aimed to develop a Vietnamese version of the PACV and examine factors associated with parental vaccine hesitancy in Hue city, Vietnam. METHODS: This study was a cross-sectional study. The English PACV was translated into Vietnamese with content and face validation. Self-administered questionnaires were distributed to 400 parents at ten commune health centres in Hue city, Vietnam. The parents were asked to answer the questionnaire again after two weeks for the test-retest reliability. The Vietnamese PACV reliability was assessed using Cronbach's alpha and McDonald's omega, and the intra-class correlation (ICC) coefficients were used for the test-retest reliability. The construct validity was tested by the hypothesis that parental vaccine hesitancy would be related to the intention of getting the children vaccinated. Exploratory factor analysis was also undertaken to determine the construct validity. Bivariate and multivariable logistic regression were used to identify the factors associated with parental vaccine hesitancy. RESULTS: The Vietnamese PACV final version (PACV-Viet) contained 14 items. Three hundred and fifteen parents returned completed questionnaires, giving a response rate of 78.8%. The Cronbach's alpha and McDonald's omega were 0.72 and 0.70, respectively. Out of 315 parents, 84 responses were returned for test-retest reliability. All ICCs were good to excellent, ranging from 0.81 to 0.99. The PACV-Viet was confirmed to have construct validity. Using the PACV-Viet, 8.9% of the parents were found hesitant to childhood vaccination. Being unemployed and having seen the news about adverse events following immunisation were associated with parental vaccine hesitancy, with AOR = 3.2 (95% CI 1.3-8.0) and AOR = 4.5 (95% CI 1.2-16.7), respectively. CONCLUSIONS: The PACV-Viet is a valid and reliable tool. Community outreach is necessary to alleviate parents' concerns about childhood vaccination.

SMS-based interventions for improving child and adolescent vaccine coverage and timeliness: a systematic review.

BACKGROUND: The aim of this review was to investigate the impact of short message service (SMS)-based interventions on childhood and adolescent vaccine coverage and timeliness. METHODS: A pre-defined search strategy was used to identify all relevant publications up until July 2022 from electronic databases. Reports of randomised trials written in English and involving children and adolescents less than 18 years old were included. The review was conducted in accordance with PRISMA guidelines. RESULTS: Thirty randomised trials were identified. Most trials were conducted in high-income countries. There was marked heterogeneity between studies. SMS-based interventions were associated with small to moderate improvements in vaccine coverage and timeliness compared to no SMS reminder. Reminders with embedded education or which were combined with monetary incentives performed better than simple reminders in some settings. CONCLUSION: Some SMS-based interventions appear effective for improving child vaccine coverage and timeliness in some settings. Future studies should focus on identifying which features of SMS-based strategies, including the message content and timing, are determinants of effectiveness.

Public health and economic benefits of seasonal influenza vaccination in risk groups in France, Italy, Spain and the UK: state of play and perspectives.

BACKGROUND: Seasonal influenza epidemics have a substantial public health and economic burden, which can be alleviated through vaccination. The World Health Organization (WHO) recommends a 75% vaccination coverage rate (VCR) in: older adults (aged ≥ 65 years), individuals with chronic conditions, pregnant women, children aged 6-24 months and healthcare workers. However, no European country achieves this target in all risk groups. In this study, potential public health and economic benefits achieved by reaching 75% influenza VCR was estimated in risk groups across four European countries: France, Italy, Spain, and the UK. METHODS: A static epidemiological model was used to estimate the averted public health and economic burden of increasing the 2021/2022 season VCR to 75%, using the efficacy data of standard-dose quadrivalent influenza vaccine. For each country and risk group, the most recent data on population size, VCR, pre-pandemic influenza epidemiology, direct medical costs and absenteeism were identified through a systematic literature review, supplemented by manual searching. Outcomes were: averted influenza cases, general practitioner (GP) visits, hospitalisations, case fatalities, number of days of work lost, direct medical costs and absenteeism-related costs. RESULTS: As of the 2021/2022 season, the UK achieved the highest weighted VCR across risk groups (65%), followed by Spain (47%), France (44%) and Italy (44%). Based on modelling, the 2021/2022 VCR prevented an estimated 1.9 million influenza cases, avoiding 375,200 GP visits, 73,200 hospitalisations and 38,400 deaths. To achieve the WHO 75% VCR target, an additional 24 million at-risk individuals would need to be vaccinated, most of which being older adults and patients with chronic conditions. It was estimated that this could avoid a further 918,200 influenza cases, 332,000 GP visits, 16,300 hospitalisations and 6,300 deaths across the four countries, with older adults accounting for 52% of hospitalisations and 80% of deaths. An additional €84 million in direct medical costs and €79 million in absenteeism costs would be saved in total, with most economic benefits delivered in France. CONCLUSIONS: Older adults represent most vaccine-preventable influenza cases and deaths, followed by individuals with chronic conditions. Health authorities should prioritise vaccinating these populations for maximum public health and economic benefits.

Parents' attitudes towards the No Jab No Play legislation in Western Australia: a mixed methods study.

BACKGROUND: Mandates provide a relatively cost-effective strategy to increase vaccinate rates. Since 2014, five Australian states have implemented No Jab No Play (NJPlay) policies that require children to be fully immunised to attend early childhood education and childcare services. In Western Australia, where this study was conducted, NJNPlay legislation was enacted in 2019. While most Australian families support vaccine mandates, there are a range of complexities and unintended consequences for some families. This research explores the impact on families of the NJNPlay legislation in Western Australia (WA). METHODS: This mixed-methods study used an online parent/carer survey (n = 261) representing 427 children and in-depth interviews (n = 18) to investigate: (1) the influence of the NJNPlay legislation on decision to vaccinate; and (2) the financial and emotional impacts of NJNPlay legislation. Descriptive and bivariate tests were used to analyse the survey data and open-ended questions and interviews were analysed using reflexive thematic analysis to capture the experience and the reality of participants. RESULTS: Approximately 60% of parents intended to vaccinate their child. Parents who had decided not to vaccinate their child/ren were significantly more likely to experience financial [p < 0.001] and emotional impacts [p < 0.001], compared to those who chose to vaccinate because of the mandate. Qualitative data were divided with around half of participants supporting childhood immunisation and NJNPlay with others discussing concerns. The themes (a) belief in the importance of vaccination and ease of access, (b) individual and community protection, and (c) vaccine effectiveness, safety and alternatives help understand how parents' beliefs and access may influence vaccination uptake. Unintended impacts of NJNPlay included: (a) lack of choice, pressure and coercion to vaccinate; (b) policy and community level stigma and discrimination; (c) financial and career impacts; and (d) loss of education opportunities. CONCLUSIONS: Parents appreciation of funded immunisation programs and mandates which enhance individual and community protection was evident. However for others unintended consequences of the mandate resulted in significant social, emotional, financial and educational impacts. Long-term evidence highlights the positive impact of immunisation programs. Opinions of impacted families should be considered to alleviate mental health stressors.

Population-based cross-sectional study of factors influencing full vaccination status of children aged 12- 23 months in a rural district of the Upper East Region, Ghana.

BACKGROUND: Achieving universal health coverage includes ensuring that children have access to vaccines that are of high quality, safe, efficacious, and affordable. The Immunisation Agenda 2030 aims to expand services to zero-dose and incompletely vaccinated children and reduce immunisation rate disparities as a contribution to vaccination equity. This study explored the factors influencing full vaccination status among children aged 12 - 23 months in a rural district of the Upper East Region of Ghana. METHODS: A population-based cross-sectional study was conducted among carers of children aged 12 -23 months in the Kassena Nankana West district. A multistage sampling technique was used to select 360 carers. Information regarding the vaccination status of children was gathered through a combination of children's health record books and carers' recollections. Information on potential determinants was also systematically collected for analysis in Stata version 15.0. RESULTS: The results showed that 76.9% (95% CI: 72.3 - 81.0) of children had full vaccinations per the national schedule. All children received at least one vaccination. A higher percentage of carers with incompletely vaccinated children reported that they had travelled with their children as the primary reason for missing certain vaccine doses. Full vaccination status was significantly associated with secondary (aOR = 2.60; 95% CI: 1.20-5.63) and tertiary (aOR = 3.98, 95% CI: 1.34-11.84) maternal educational level, being in a partnership relationship (aOR = 2.09, 95% CI: 1.03-4.25), and residing in close proximity to healthcare facilities (aOR = 0.41, 95% CI: 0.21-0.80). CONCLUSIONS: Our study found that nearly one-quarter of children aged 12-23 months in the study setting are underserved with vaccination services for a variety of reasons. Effectively reaching these children will require strengthening health systems, including eliminating vaccine shortages, addressing the unique challenges faced by unmarried women with children aged 12-23 months, and improving accessibility to vaccination services.

Uptake of intra-muscular vitamin K administration after birth: A national cohort study.

AIM: A long-acting monoclonal antibody against RSV (nirsevimab), given as an injection shortly after birth, is currently being rolled out globally. Carer acceptance of intra-muscular (IM) vitamin K, another injection given shortly after birth, could serve to indicate the acceptability of nirsevimab. METHODS: We analysed a national dataset of postnatal health visitor visits in Scotland; individual-level data on gestation were not available. The primary outcome measure was the modality of administration of vitamin K; potential explanatory variables were maternal age, infant ethnicity, English as a first language, and measures of socio-economic deprivation. We examined associations between IM vitamin K administration or oral/no vitamin K and each explanatory variable. RESULTS: From 2019 to 2021, questionnaires were available for 142 857 infants; data was missing for 2.7%. IM Vitamin K uptake was high: 95.5% of carers consented, with 1.1% requesting oral vitamin K and 0.9% refusing vitamin K altogether. Infant ethnicity, use of English as a first language, socio-economic status and maternal age were not associated with reduced uptake of IM vitamin K. CONCLUSION: If IM Vitamin K administration is a valid proxy measure for nirsevimab acceptance, we did not identify groups that might require increased engagement prior to nirsevimab roll-out.

Maternal singing reduced pain indexes in 2-month-old infants and increased proximity during vaccinations.

AIM: Immunisation is a global health priority, but methods of non-pharmacological pain relief are not widely used in routine clinical practice. In this study, we set out to investigate the effects of maternal singing during the routine vaccination of infants. METHODS: We recruited 67 mother-infant pairs at Health Centres in the Aosta Region of Italy. Infants aged 2-4 months were randomly allocated to a singing intervention group or to a control group whose injections were administered following standard practice. Pre- and post-immunisation pain was blindly assessed using the Modified Behavioural Pain Scale, and mother-infant proximity indexes were assigned based on muted video-tracks. RESULTS: When assessed for pain, the infants in the maternal singing group were assigned significantly lower movement indexes (p = 0.032) and marginally significantly lower cry indexes (p = 0.076). A higher frequency of mother-to-infant gaze (p < 0.005) was observed in the singing group dyads. Finally, the intervention group mothers' self-perceived ease in singing was correlated with their previous singing experience and with lower anxiety following the vaccination procedure (p < 0.05). CONCLUSION: Maternal singing during immunisation procedures benefits both mothers and babies. The practice of singing is a biologically rooted and adaptive form of intuitive parental communication that should be encouraged, especially in at-risk populations.