Early Vaccination Research Articles

Unlocking the potential for microbiome-based therapeutics to address the sustainable development goal of good health and wellbeing.

Recent years have witnessed major advances and an ever-growing list of healthcare applications for microbiome-based therapeutics. However, these advances have disproportionately targeted diseases common in high-income countries (HICs). Within low- to middle-income countries (LMIC), opportunities for microbiome-based therapeutics include sexual health epidemics, maternal health, early life mortality, malnutrition, vaccine response and infectious diseases. In this review we detail the advances that have been achieved in microbiome-based therapeutics for these areas of healthcare and identify where further work is required. Current efforts to characterise microbiomes from LMICs will aid in targeting and optimisation of therapeutics and preventative strategies specifically suited to the unmet needs within these populations. Once achieved, opportunities from disease treatment and improved treatment efficacy through to disease prevention and vector control can be effectively addressed using probiotics and live biotherapeutics. Together these strategies have the potential to increase individual health, overcome logistical challenges and reduce overall medical, individual, societal and economic costs.

Relative effectiveness of high-dose vs. standard-dose quadrivalent influenza vaccine according to time of day of vaccination: a post-hoc analysis of the DANFLU-1 randomised clinical trial

Abstract Background Circadian variations have been shown to affect antibody response following vaccination. We sought to evaluate whether time of day of vaccination (ToV) modified the relative effectiveness of high-dose (QIV-HD) vs. standard-dose (QIV-SD) quadrivalent influenza vaccination, and further whether ToV was independently associated with hospitalisations and mortality. Methods This is a post-hoc analysis of the DANFLU-1 trial which was a randomized trial of QIV-HD vs. QIV-SD in adults aged 65-79 years conducted during the 2021-2022 influenza season. Vaccination took place between 7:05 AM and 8:08 PM. For this study, we stratified participants into early and late vaccination groups according to ToV before or after 11 AM, respectively. Prespecified outcomes included hospitalisations for pneumonia or influenza, respiratory disease, cardiovascular disease, and cardio-respiratory disease as well as all-cause hospitalisations and mortality. Hospitalisations were analysed as recurrent events using negative binomial regression, while mortality was analysed using Cox proportional hazard models, both of which were also used to test for interaction. For multivariable analysis, models were adjusted for baseline risk factors including sex, age, and multiple lung diseases. ToV was furthermore assessed as a continuous variable with 2-hour increments. Results In the final study population, the early group consisted of 5,371 (43%) participants (mean age 71.6±3.9 years, male sex 53.6%, QIV-SD 50.1%), while the late group consisted of 7,106 (57%) (mean age 71.8±4.0 years, male sex 52.4%, QIV-HD 49.9%). During follow-up, we observed 43 hospitalisations for pneumonia or influenza, 76 respiratory hospitalisations, and 62 mortalities. In recurrent event analysis, QIV-HD was associated with lower incidence of hospitalisation for pneumonia or influenza compared with QIV-SD irrespective of whether administered early (IRR 0.17 (95% CI 0.03-0.86), p=0.032) or late (IRR 0.37 (95% CI 0.16-0.88), p=0.024) (p-value for interaction = 0.69) (Figure 1). Effect estimates were consistent for all outcomes excluding cardiovascular hospitalisations regardless of early or late vaccination, and no effect modification was found (Figure 1). Interestingly, late vaccination was associated with higher incidence rate of respiratory hospitalisation (IRR 3.00 (95% CI 1.13-7.98), p=0.024, Figure 2), irrespective of vaccine type. The same association was found for ToV as a continuous variable (IRR 1.28 per 2-hour increment (95% CI 1.02-1.60), p=0.035). All above associations remained significant in multivariable analysis. Conclusion QIV-HD was associated with lower incidence of hospitalisation for pneumonia or influenza regardless of time of day for vaccination. In addition, later vaccination was associated with higher incidence of respiratory hospitalisation independent of vaccine type and known risk factors. Due to low power, however, this finding should be regarded as exploratory.Figure 1:Forest plotFigure 2:Incidence rates

Trends in influenza vaccination and its determinants among pregnant French women between 2015 and 2020: A single-center study

ABSTRACT In 2016, only 7% of French women had received an influenza vaccination during their pregnancy. In this vaccine-averse country, the possibility of reaching the rates of 50% observed in other countries remains unknown. To measure the rate of influenza vaccination in a French university maternity. To study its evolution and determinants over the last 5 years. Single-center observational study of all women who gave birth during March 2020 in this maternity. Comparison with rates observed in 2015 in the same conditions. Of the 337 women included in the study, 202 received a vaccination during pregnancy (59.9%). After logistic regression, the factors significantly associated with achieving vaccination were the offer of vaccination during pregnancy, odds ratio (ORa) 26.2 [7.0; 98.2]; previous vaccination, ORa 20.3 [9.6; 42.6]; high education level, ORa 2.9 [1.3; 6.2]; delivery of a CERFA government reimbursement form, ORa 2.5 [1.3; 4.8]; a vaccination offer made by a general practitioner, ORa 2.1 [1.0; 4.4] and not by a hospital midwife, ORa 0.3 [0.1; 0.6]. The rate of vaccination increased from 35% to 59.9% between 2015 and 2020 ( p < .001), with a significant increase in the offer of vaccination during pregnancy (+14.6%) - especially by a general practitioner (+17.2%) - and in the rate of women with earlier vaccination (+13.6%). In France, vaccination rates above 50% are possible at a center level. A proposal of vaccination during pregnancy – especially by the general practitioner – seems to be a determining factor in this development.

Exploring the evolution of rotavirus vaccines and its impact on global public health

Rotavirus, a prevalent pathogen within the Reoviridae family, poses a significant threat to children, particularly infants and young children, causing gastroenteritis. High transmissibility and severe diarrhea lead to dehydration, severe infection, and death, especially in regions with limited resources and poor sanitation. Rotavirus infections spread through contaminated food, water, and fomites, primarily affecting developing countries due to inadequate sanitation standards. Vaccination has emerged as a crucial preventive strategy against rotavirus gastroenteritis, with the aim of reducing the global burden of the disease. The early rotavirus vaccines, exemplified by Rota-Shield, faced challenges such as safety concerns, emphasizing the importance of rigorous safety evaluation and post-marketing surveillance. Subsequent vaccines, Rotarix and RotaTeq, have shown efficacy and safety, significantly reducing rotavirus-related morbidity and mortality worldwide. The global implementation of rotavirus vaccination programs has expanded vaccine access, leading to a decrease in disease incidence and hospitalizations. Despite these achievements, challenges persist, such as hesitantness to apply the vaccine and disparities in vaccine access. Future research directions include the development of next-generation vaccines with greater coverage and the exploration of novel vaccine delivery strategies. A sustained commitment to research, infrastructure strengthening, and community involvement is essential to eliminate the burden of rotavirus disease worldwide. The objective of this review is to explore the evolution of rotavirus vaccines and impact on global public health.

The 13-year long-term follow-up on the effectiveness and immunogenicity of the quadrivalent human papillomavirus vaccine in Chinese females vaccinated at 20–45 years of age

ABSTRACT The quadrivalent human papillomavirus (qHPV) vaccine demonstrated high efficacy against vaccine-type-related precancers in Chinese females through a 6.6-year double-blind, randomized control trial (V501–041, NCT00834106). We present results for its long-term follow-up (LTFU) phase, evaluating vaccine effectiveness and immunogenicity throughout 13 years post Dose 1. Participants receiving qHPV vaccines at ages 20–45 in the V501–041 study constituted the early vaccination group (EVG). Those who received the placebo in V501–041 but were vaccinated during 2018–2020 formed the catch-up vaccination group (CVG), while the control group (CG) comprised those remaining unvaccinated throughout V501–041 and LTFU. The primary endpoint was histopathologically-confirmed cervical intraepithelial neoplasia (CIN) 2+ tested PCR-positive for HPV-16/18. Antibodies against HPV-6, 11, 16, and 18 were assessed using an immunoglobulin G (IgG) Luminex immunoassay at year 13. A total of 1100 participants from V501–041, of whom 978 were followed in LTFU, were included with a median follow-up of 152.2 months. No cases of the primary endpoint were observed in the EVG during 5513.6 person-years of follow-up, while one case was observed in the CG over 2951.4 person-years of follow-up, indicating a 100% risk reduction in the EVG compared to the CG. In the CVG, no cases were detected from vaccination to the latest follow-up (0.0 per 10 000 person-years), contrasting with an incidence of 22.3 per 10 000 person-years prior to vaccination. Seropositivity rates at year 13 remained >92% (for HPV-6/11/16) and 84% (HPV-18). These findings demonstrated continued vaccine protection against cervical precancers and sustained immunogenicity through 13 years post-vaccination. Trial Registration The LTFU study was registered at the Chinese Clinical Trial Registry, ChiCTR2100052313.

Impact and Effectiveness of COVID-19 Vaccines Based on Machine Learning Analysis of a Time Series: A Population-Based Study.

Background: Although confirmed cases of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been declining since late 2020 due to general vaccination, little research has been performed regarding the impact of vaccines against SARS-CoV-2 in Spain in terms of hospitalizations and deaths. Objective: Our aim was to identify the reduction in severity and mortality of coronavirus disease 2019 (COVID-19) at a nationwide level due to vaccination. Methods: We designed a retrospective, population-based study to define waves of infection and to describe the characteristics of the hospitalized population. We also studied the rollout of vaccination and its relationship with the decline in hospitalizations and deaths. Finally, we developed two mathematical models to estimate non-vaccination scenarios using machine learning modeling (with the ElasticNet and RandomForest algorithms). The vaccination and non-vaccination scenarios were eventually compared to estimate the number of averted hospitalizations and deaths. Results: In total, 498,789 patients were included, with a global mortality of 14.3%. We identified six waves or epidemic outbreaks during the observed period. We established a strong relationship between the beginning of vaccination and the decline in both hospitalizations and deaths due to COVID-19 in all age groups. We also estimated that vaccination prevented 170,959 hospitalizations (CI 95% 77,844-264,075) and 24,546 deaths (CI 95% 2548-46,543) in Spain between March 2021 and December 2021. We estimated a global reduction of 9.19% in total deaths during the first year of COVID-19 vaccination. Conclusions: Demographic and clinical profiles changed over the first months of the pandemic. In Spain, patients over 80 years old and other age groups obtained clinical benefit from early vaccination. The severity of COVID-19, in terms of hospitalizations and deaths, decreased due to vaccination. Our use of machine learning models provided a detailed estimation of the averted burden of the pandemic, demonstrating the effectiveness of vaccination at a population-wide level.

CRM197-scaffolded vaccines designed by epitope grafting ameliorate cognitive decline in an Alzheimer's disease model

Alzheimer's disease (AD) is the leading cause of dementia in the elderly. Amyloid-beta (Aβ) plaque accumulation and tau neurofibrillary tangles (NFTs) formation in the brain are major neuropathological hallmarks of AD. Immunotherapies targeting Aβ and/or tau are deemed the most promising approaches for AD. Administrations with monoclonal antibodies against Aβ have yielded substantial breakthroughs clinically. Most vaccines tested clinically so far failed to prove efficacious in large part due to inappropriate design of vaccine antigens. In this study, a structure-guided approach was employed to design novel antigens targeting Aβ and/or tau by grafting multiple copies of Aβ and/or tau B-cell epitope peptide onto CRM197, which is the most widely used carrier protein in polysaccharide conjugate vaccines. The immunogenicity of the vaccines was evaluated in BALB/c mice and the efficacy was tested in a transgenic mouse model of human amyloidopathy. The antigens were highly immunogenic early vaccination substantially ameliorated cognitive decline in APP/PS1 mice and significantly reduced insoluble Aβ42/40 in the brains. These results demonstrate that the engineered antigens have protective effects on AD mice, offering a promising translatable strategy for the prevention and/or treatment of AD.

Routine vaccine uptake in school-aged autistic and non-autistic youth: A linked database study.

This study was conducted to determine whether school-aged autistic youth received routine vaccines at a lower rate than their non-autistic peers. In Nova Scotia (NS), Canada, vaccines routinely delivered in early adolescence are administered to Grade 7 students through a school-based Public Health vaccination program. NS youth eligible to receive Grade 7 vaccinations between 2011 and 2017 were included in this study. Autism spectrum disorder (ASD) diagnoses were determined from administrative health data. Rates of receipt of any Grade 7 vaccine and of individual vaccines were compared between autistic and non-autistic youth. Subgroup analyses included comparing Grade 7 vaccine receipt between autistic youth and their non-autistic siblings and early childhood vaccine receipt between autistic and non-autistic cohorts. The rates of receipt of any vaccine were 73% among 916 autistic youth and 82% among 49,599 non-autistic youth (adjusted relative risk = 0.91; 95% confidence interval = 0.87-0.95). Similar results were found for individual vaccines. Subgroup analyses revealed lower rates of Grade 7 vaccine receipt among autistic youth compared to among their non-autistic siblings. Rates of early childhood vaccine receipt did not differ between autistic and non-autistic cohorts. Autistic youth were under-vaccinated compared to their non-autistic peers for Grade 7 vaccinations. Lower vaccination rates in autistic youth than in their non-autistic siblings suggest that setting-related factors may contribute more to the under-vaccination of autistic youth than parental vaccine hesitancy. Barriers to vaccine uptake for school-aged autistic youth, including those unique to school-based vaccination programs, must be explored and addressed.

Effective reduction of pathogenic Escherichia coli and long-term immunity in pigs through early parenteral vaccination

ABSTRACT The present study aimed to examine the ability of a parenteral vaccine of direct application in suckling pigs to generate adaptive immunity against pathogenic Escherichia coli under field conditions as well as the long-term immune response at the end of productive life and the influence on the prevalence of pathogens involved in the Porcine Enteric Disease Complex (PEDC). Pigs were divided into vaccinated (n = 1,893) and non-vaccinated (control, n = 1,869) groups. We collected fecal swabs from nursery pigs presenting diarrhea and intestinal tissue at slaughter to assess E. coli virulence factors genes, PEDC pathogens, histology, IgA-producing cells, and cytokines levels. Fecal swabs: vaccinated group 0% pathogenic E. coli vs. 94.1% in control (p < 0.0001). Intestinal samples: Vaccinated group 35% positivity for E. coli vs. 85% in control (p = 0.001). PEDC pathogens: Only Lawsonia intracellularis was identified (40% of ileum and 20% of colon samples in vaccinated vs. 100% of ileum and 70% of colon in the control). Vaccinated had more intestine cellular infiltrate (p < 0.028), IgA-producing cells (p < 0.01), and inflammatory cytokines. The parenteral vaccine against E. coli for suckling pigs may be a strategy to control E. coli infection throughout pigs’ lives and our results suggest a possible interaction with L. intracellularis.

Development of Influenza-Specific CD4 T Cell-Mediated Immunity in Children Following Inactivated Influenza Vaccination.

While both cellular and humoral immunity are important in immunologic protection against influenza, how the influenza-specific CD4 T cell response is established in response to early vaccination remains inadequately understood. In this study, we sought to understand how the CD4 T cell response to IIV is established and develops throughout early childhood. Influenza-specific CD4 T cell responses were quantified following IIV over two influenza seasons in 47 vaccinated children between 6 months and 8 years of age who had no documented history of natural influenza infection during the study. PBMCs were stimulated with peptide pools encompassing the translated regions of the pH1, H3, HAB, and NP proteins and CD4 T cell responses were assessed via multiparameter flow cytometry. There was boosting of H3- and HAB-specific CD4 T cells but not cells specific for the pH1 HA protein post-vaccination. A positive correlation between age and the magnitude of the influenza-specific CD4 T cell response was seen, with an overall greater magnitude of IFNγ-producing cells in subjects ≥3 years of age. Changes in CD4 T cell functionality were also noted in older compared to younger children, with increases in CD4 T cells producing IFNγ and TNF or IL-2 as well as IFNγ alone. IIV elicits a CD4 T cell response to H3 and HAB, with increases in the magnitude of the CD4 T cell response and changes in cellular functionality throughout childhood. This suggests that repeated influenza vaccination contributes to the development of anti-influenza CD4 T cell memory in children.

Which Stranger's Disease? Immigration, Immunization, and the Whitening of Cuba in the Age of Atlantic Revolutions.

In 1804, Cuban physician Tomás Romay tried and failed to create the first yellow fever vaccine. The article analyzes his experimental efforts, foregrounding the enslaved and enlisted subjects at the center of this early vaccine trial. Though a scientific failure, this brief experiment, the desires and logics embedded within it, and the measures deployed in its wake - in the form of European whitening campaigns - allow us to consider the political uses of immunity during the Age of Atlantic Revolutions. Historicizing these events within the wider geopolitics of the Caribbean, the article explicates the central role that yellow fever immunization played in Cuban authorities' attempts to shore up their political and economic sovereignty in the midst of anti-colonial and anti-slavery resistance. As such, it shows how yellow fever and its threat to social and economic order fits within a broader history of vaccination as a mechanism of colonial governance. Finally, by situating Cuban efforts to prevent yellow fever alongside the health concerns of enslaved people - concerns that arguably informed their resistance to slavery - the article also demonstrates how ideas about immunity and political belonging increasingly intersected through whiteness as an elite ideal in the era that Cuba first became a slave society.

When to vaccinate for seasonal influenza? Check the peak forecast.

Seasonal influenza infects 5-20% of people every year in the United States, resulting in hospitalizations, deaths, and adverse economic impacts. To mitigate these impacts, influenza vaccines are developed and distributed annually; however, growing evidence suggests that vaccine effectiveness (VE) wanes over the course of a flu season. Delaying influenza vaccination for older adults has attracted attention as a potential public health strategy. However, given the uncertainties in seasonal peak, vaccine effectiveness, and waning rates, postponing vaccination could also lead to increased morbidity, motivating an evaluation of a range of potential scenarios. We systematically investigated a broad range of vaccination start times for five age groups under six combinations of initial effectiveness and waning rates, based on influenza cases and vaccine uptake data from 10 influenza seasons. We defined the most favorable vaccination schedule as the one that resulted in the greatest reduction in disease burden. In scenarios with fast waning, all age groups benefit from delaying vaccination regardless of initial VE and peak timing. In scenarios with slower waning, results are mixed. For the ≥65 group, high initial VE and slow waning suggests that in early-peaking seasons, early vaccination most effectively reduces disease burden, while in late-peaking seasons delaying vaccination is most effective. For the ≥65 group in medium and low initial VE, and slow waning scenarios, delaying vaccination appears to prevent the greatest number of cases, regardless of whether the season peaks early or late. The most favorable vaccination schedule is sensitive to changes in initial VE, waning rate, and peak timing. Given estimates of these quantities from statistical and immunological models and observations, our methods can inform vaccination recommendations in order to most effectively reduce the annual disease burden caused by seasonal influenza. Specifically, accurate peak timing forecasts for the upcoming season have the potential to guide decisions on when to vaccinate.

SARS-COV-2 breakthrough infection and its covariates among healthcare providers of a hospital in Bangladesh during the omicron wave

IntroductionBreakthrough infection by SARS-COV-2 virus among vaccinated individuals has been reported from all over the world and it has created a substantial challenge in designing strategies to live with the virus in the post-pandemic era. Factors affecting the extent and nature of breakthrough infection are still not fully understood and those are known to vary depending on host and agent factors. Health Care Workers (HCWs), especially in hospital settings, are front-liners in combating the epidemic and, consequently, they are more vulnerable to breakthrough infection by SARS-COV-2. Like most of the countries of the world, Bangladesh went through several waves of COVID-19 and the last (3rd wave) was the widespread Omicron wave during the winter of 2022. HCWs in Bangladesh have been disproportionately affected by the virus. Under this context, the aim of the present study was to explore breakthrough infection (BTI) and its host-related covariates among HCWs of a COVID-dedicated city-based hospital during the Omicron wave in Bangladesh. Materials and methodsAn observational cross-sectional study was conducted on 267 HCWs of the Narayanganj Tertiary (300-bed) hospital during February–March 2022 which coincided with the terminal part of the 3rd wave. Data were collected by trained Field Assistants using Interviewer-administered Data Collection Forms with Questionnaires as instruments. Previous COVID-19 status (any time after the onset of the pandemic and within last 3 months) was explored by the history of specific symptoms as well as by the confirmatory rtPCR test reports from DGHS approved laboratories Anti-nucleocapsid antibody (Anti-N-Ab) in venous blood samples, assayed by a chemiluminescent ELISA technique, was used as a seroprevalence-based marker of breakthrough infection during the preceding few months. Data were analyzed by bivariate as well as multivariate statistics using the IBM-SPSS software. ResultsThe median age (range) of the HCWs was 38 (21–65) years; Body Mass Index (BMI, kg/m2) 25 (15–49); and Waist-Hip Ratio (WHR) was 0.92 (0.46–1.21). The male subjects had significantly higher median age (p = 0.01) and higher WHR (p = 0.001) as compared to the female subjects. As per the BMI category, subjects with overweight and obesity constituted 83.3 % of the male subjects as compared to 61.6 % of the female subjects (p = 0.001). The time lapse between receiving of 3rd dose and blood sampling was significantly higher among females compared to males (median days 60 vs 49, p < 0.02) indicating earlier vaccination with 1st booster dose among females. A proportion of 51.85 % male and 49.68 % female subjects showed Anti-N-Ab positivity; there was no significant difference between the gender groups. Also, there was no significant difference among male and female subjects regarding the Ab levels. On Spearman correlation analysis, a tendency of association of WHR with Ab level was observed among the male subjects; however, the association did not show statistical significance (p = 0.09). On binary logistic regression Ab positivity was found to be independently associated with WHR (p = 0.03), and prior SARS-COV-2 infection within the last 3 months (p = 0.02) among males. When all the subjects were considered together, COVID symptom positivity during the last 3 months (p = 0.067) and receiving the 1st booster dose (p = 0.07) showed a tendency of association with Ab positivity. On multiple regression analysis, Ab levels showed a negative association with WHR (p = 0.035) among males. ConclusionsMore than 50 % of the vaccinated hospital-based HCWs in Bangladesh suffered from BTI during the winter of 2022 when the Omicron wave (the 3rd wave) of COVID-19 was at its peak. The data also indicate that overweight and obesity are major host-related risk factors underlying BTI. Inadequate coverage by a booster dose seems to be another determinant of BTI and the level of immune response in this population.

Simultaneous Use of Iron/Anticoccidial Treatment and Vaccination against Oedema Disease: Impact on the Development of Serum-Neutralising Antibodies, Hematinic and Anticoccidial Activities in Piglets.

Oedema disease (OD) in weaned piglets is caused by shigatoxigenic Escherichia coli (STEC), which produces the Stx2e toxin. The disease is controlled by early vaccination (for example, with Ecoporc Shiga®). Iron-deficiency anaemia (IDA) and cystoisosporosis are the most common clinical conditions in piglets. These conditions are managed mainly by the intramuscular injection of iron and application of toltrazuril (for example, Forceris®). In the present study, we sought to evaluate any effect on the efficacy of OD vaccination and iron/anticoccidial treatment resulting from a simultaneous application. An evaluation was carried out by measuring the development of neutralising antibodies against the Stx2e toxin, hematinic indices and oocysts shedding. Six litters from Stx2e-antibody-negative sows were included in the study, with 12 piglets in each litter. The piglets were randomly allocated into two groups on their second day of life (DOL): (T1) iron/anticoccidial treatment and vaccine were administered on different days, and (T2) products were administered simultaneously. Blood samples were collected to determine the levels of serum-neutralising antibodies, haemoglobin and haematocrit. Faecal matter was examined for the presence of oocysts of Cystoisospora suis. No differences were found between the two groups in terms of the development of neutralising antibodies. The levels of haemoglobin and haematocrit were lower (p < 0.05 and p = 0.08, respectively) when iron/anticoccidial treatment and vaccine were applied simultaneously but within the optimal range, based on current interpretive criteria for IDA. Oocysts were not detected in the faecal samples from the animals in either group. In conclusion, we found that, under the conditions of our study, the efficacy of OD vaccination and iron/anticoccidial treatment was not affected by the simultaneous use.

Contradictory mortality results in early 2-dose measles vaccine trials: interactions with oral polio vaccine may explain differences

ObjectivesBetween 2003 and 2019, three trials (randomised controlled trials [RCTs]) in Guinea-Bissau randomised infants to an early 2-dose measles vaccine (MV) schedule at 4 and 9 months vs standard MV at 9 months. The RCTs produced contradictory mortality results; the effect being beneficial in the 2-dose group in the first but tending to have higher mortality in the last two RCTs. We hypothesised that increased frequency of campaigns with oral polio vaccine (C-OPV) explained the pattern. MethodsWe performed per-protocol analysis of individual-level survival data from the three RCTs in Cox proportional hazards models yielding hazard ratios (HR) for the 2-dose vs the 1-dose MV group. We examined whether timing of C-OPVs and early administration of OPV0 (birth to day 14) affected the HRs for 2-dose/1-dose MV. ResultsThe combined HR(2-dose/1-dose) was 0.79 (95% confidence interval: 0.62-1.00) for children receiving no C-OPV-before-enrolment, but 1.39 (0.97-1.99) for those receiving C-OPV-before-enrolment (homogeneity, P = 0.01). C-OPV-before-enrolment had a beneficial effect in the 1-dose group but tended to have a negative effect in the 2-dose group, especially in females. These effects were amplified further by early administration of OPV0. ConclusionIn the absence of C-OPVs, an early 2-dose MV strategy had beneficial effects on mortality, but frequent C-OPVs may have benefitted the 1-dose group more than the 2-dose MV group, leading to varying results depending on the intensity of C-OPVs.

Evaluation of Rhode Island's Early Geographic COVID-19 Vaccine Prioritization Policy.

Objectives. To determine whether geographic prioritization of limited COVID-19 vaccine supply was effective for reducing geographic disparities in case rates. Methods. Rhode Island allocated a portion of the initial COVID-19 vaccine supply to residents of Central Falls, a community already affected by structural policies and inadequate systems that perpetuate health inequities and experiencing disproportionately high COVID-19 morbidity and mortality. The policy was implemented with a culturally and linguistically appropriate community engagement plan and was intended to reduce observed disparities. Using a Bayesian causal analysis with population surveillance data, we evaluated the impact of this prioritization policy on recorded cases over the subsequent 16 weeks. Results. Early geographic prioritization of Central Falls accelerated vaccine uptake, averting an estimated 520 cases (95% confidence interval = 22, 1418) over 16 weeks and reducing cases by approximately 34% during this period (520 averted vs 1519 expected without early prioritization). Conclusions. Early geographic prioritization increased vaccine uptake and reduced cases in Central Falls, thereby reducing geographic disparities. Public Health Implications. Public health institutions should consider geographic prioritization of limited vaccine supply to reduce geographic disparities in case rates. (Am J Public Health. 2024;114(S7):S580-S589. https://doi.org/10.2105/AJPH.2024.307741).

Variant-specific antibody profiling for tracking SARS-CoV-2 variant infections in children and adolescents.

Monitoring the seroprevalence of SARS-CoV-2 in children and adolescents can provide valuable information for effective SARS-CoV-2 surveillance, and thus guide vaccination strategies. In this study, we quantified antibodies against the spike S1 domains of several SARS-CoV-2 variants (wild-type, Alpha, Delta, and Omicron variants) as well as endemic human coronaviruses (HCoVs) in 1,309 children and adolescents screened between December 2020 and March 2023. Their antibody binding profiles were compared with those of 22 pre-pandemic samples from children and adolescents using an in-house Luminex®-based Corona Array (CA). The primary objectives of this study were to (i) monitor SARS-CoV-2-specific antibodies in children and adolescents, (ii) evaluate whether the S1-specific antibody response can identify the infecting variant of concern (VoC), (iii) estimate the prevalence of silent infections, and (iv) test whether vaccination or infection with SARS-CoV-2 induce HCoV cross-reactive antibodies. Both SARS-CoV-2 infection and vaccination induced a robust antibody response against the S1 domain of WT and VoCs in children and adolescents. Antibodies specific for the S1 domain were able to distinguish between SARS-CoV-2 VoCs in infected children. The serologically identified VoC was typically the predominant VoC at the time of infection. Furthermore, our highly sensitive CA identified more silent SARS-CoV-2 infections than a commercial ELISA (12.1% vs. 6.3%, respectively), and provided insights into the infecting VoC. Seroconversion to endemic HCoVs occurred in early childhood, and vaccination or infection with SARS-CoV-2 did not induce HCoV S1 cross-reactive antibodies. In conclusion, the antibody response to the S1 domain of the spike protein of SARS-CoV-2 is highly specific, providing information about the infecting VoC and revealing clinically silent infections.

Mortality during the SARS-CoV-2 Pandemic: A Comparative Analysis between Lombardy in Italy and Israel.

Background: This retrospective study contrasts the impact of the SARS-CoV-2 pandemic in Lombardy (Italy) and Israel, focusing on mortality, healthcare response, public health measures, and demographics. Methods: We analyzed SARS-CoV-2 data from Lombardy and Israel covering four viral waves. Data included infection rates, hospitalizations, and mortality. In Lombardy, healthcare data were collected from the administrative database of the Lombardy Welfare Directorate; in Israel, they were collected from Clalit Health Services and the Israeli Ministry of Health's COVID-19 database. Statistical analyses compared trends in infection rates, demographics, and mortality rates across the four viral waves by using logistic and linear regression models and adjusting for age, sex, and comorbidities. Results: Lombardy exhibited significantly higher SARS-CoV-2 infections and COVID-19 hospitalization rates during the first wave than Israel, with 71,558 cases over a population sample of ~10 million versus 5741 over a population sample of ~4.7 million in Israel. The majority of cases in Israel were managed at home, with 18 cases only (0.3%) requiring intensive care unit (ICU) hospitalization during the first wave, compared to 4104 (5.7%) cases in Lombardy. Israel's vaccination campaign began earlier, so that by the fourth wave, 439,545 (42.2%) people in Israel were fully vaccinated with three doses, compared to 214,542 (22.9%) in Lombardy. Mortality decreased over time in both sites, dropping from 103 cases (1.8%) to 1550 (0.1%) in Israel and from 13,372 (18.7%) to 4388 (0.3%) in Lombardy. Conclusions: Early public health interventions and vaccination were crucial in managing the SARS-CoV-2 impact.

Risk of healthcare visits from influenza in subjects with diabetes and impacts of early vaccination

IntroductionThe objective of this study was to determine the burden of influenza disease in patients with or without diabetes in a population of American adults to understand the benefits of...

The effect of public tolerance towards corruptive behaviour on healthcare efficiency and equity – The case of the UK's COVID-19 vaccination programme

Over the past four years, the COVID-19 pandemic has caused significant uncertainty, suffering, and economic disruption on a global scale. In response, governments have been under pressure to ensure equitable vaccine access while meeting vaccination targets quickly. These challenging circumstances created opportunities for nepotism and bribery, increasing attention to corruption risks associated with the pandemic response. This study investigates the relationship between public attitudes towards corruptive behaviour and the efficiency and equity of the UK's COVID-19 vaccination programme. It integrates primary data on public tolerance towards corruptive behaviour with secondary data on the efficiency of the vaccination program at the local authority level in England and Scotland. Employing a survival analysis approach, we estimate Cox Proportional Hazards Models to examine the time required to reach vaccination targets. Our findings suggest moderate tolerance towards corruptive behaviour among the British public, with 28% of survey participants considering monetary bribery and 34% considering nepotism/favouritism as acceptable means to secure early vaccination access. Notably, while public tolerance towards corruptive behaviour generally had a negative impact on the efficiency of the local rollout of the vaccination programme, it appeared to have accelerated its rollout in politically aligned local authorities governed by the Conservative and Unionist Party. However, this increase in efficiency seems to have come at the cost of reduced equity in vaccine distribution. These findings suggest a trade-off between efficiency and equity in vaccine distribution during public health crises, emphasising the need for balanced health policies that ensure fair and effective distribution of vaccines in the future.