Human Vaccines & Immunotherapeutics

BackgroundThe SARS-CoV-2 LP.8.1 subvariant was incorporated into the 2025-2026 U.S. COVID-19 vaccines (mRNA-1273.251 and mRNA-1283.251). We evaluated immunogenicity and safety of these vaccines against vaccine-matched and emerging variants in individuals aged [≥]65 and those aged 12-64 years at high-risk of severe COVID-19. MethodsData were generated from: (1) two independent, ongoing, phase 3b/4, open-label, single-arm studies in which participants received a single dose of 50-{micro}g mRNA-1273.251 (n=103; median age, 64.0 years) or 10-{micro}g mRNA-1283.251 (n=172, median age, 59.0 years) and followed through Day 29 post-vaccination; neutralizing antibodies (nAb) were measured at baseline (Day 1) and Day 29 using a pseudovirus neutralization assay against the vaccine-matched LP.8.1 variant; (2) Day 29 immunogenicity against circulating variants (BA.3.2.2, XFG, and NB.1.8.1) was assessed in a randomly selected subset; and (3) immune-escape potential was estimated using predictive modeling. Unsolicited adverse events (AEs), including serious AEs, leading to study withdrawal, and those of special interest, were monitored. ResultsBoth vaccines elicited robust nAbs at Day 29 against LP.8.1 (geometric mean fold-rise from baseline: 12-64 years, mRNA-1273.251, 26.3; mRNA-1283.251, 53.0; [≥]65 years, mRNA-1273.251, 15.4; mRNA-1283.251, 36.7) and circulating variants. Model-based estimates with mRNA-1273.251 were consistent with clinical data and indicated the highest responses against LP.8.1 and lower responses against BA.3.2.2. No vaccine-related AEs were reported in either study. ConclusionsmRNA-1273.251 and mRNA-1283.251 were well tolerated through Day 29 and elicited robust nAbs against vaccine-matched and circulating variants. In predictive models, BA.3.2.2 had the highest relative risk of immune escape following mRNA-1273.251 vaccination. SUMMARYLP.8.1-containing mRNA-1273.251 and mRNA-1283.251 vaccines given as a single dose were well tolerated and induced robust Day 29 neutralizing antibodies against LP.8.1 and circulating variants.

BackgroundInitial reports from the Netherlands indicate a decline in routine childhood vaccination uptake during and after the COVID-19 pandemic, with emerging evidence of reduced parental vaccine confidence. This study aimed to evaluate the long-term impact of the COVID-19 pandemic on routine childhood vaccination uptake. MethodsWe conducted a retrospective nationwide cohort study including all children born in the Netherlands in 2016-2024. First-dose DTaP-IPV vaccination status by age six months was obtained from the national immunisation register. National trends in vaccination uptake across pre-pandemic, pandemic, and post-pandemic periods were assessed using interrupted time series analyses. To further assess the independent effect of the pandemic, a matched-sibling analysis compared vaccination uptake within families before, during and after the pandemic. ResultsInterrupted time series analyses showed significant immediate decreases in vaccination uptake both at the start and end of the pandemic, accompanied by a continuing downward trend during the pandemic (OR 0.984, 95%CI 0.982-0.985) that further declined after its end (OR 0.995, 95%CI 0.994-0.997). In the matched-sibling analysis children eligible during and after the pandemic had lower odds of being vaccinated (pandemic: OR 0.66, 95%CI 0.55-0.80; post-pandemic: OR 0.20, 95%CI 0.17-0.25) compared to their pre-pandemic siblings. Also, later birth order was associated with lower odds compared to first-born siblings (second-born: OR 0.42, 95%CI 0.37-0.48). ConclusionsBoth analyses indicate a negative impact of the COVID-19 pandemic on parental vaccination decisions, which may reflect lingering pandemic effects or new post-pandemic factors, highlighting the need for further research into the drivers of vaccination uptake changes in the post-pandemic era.

Since the cessation of real-time monitoring of COVID-19 hospitalizations in early 2024, the burden of and vaccine effectiveness (VE) against severe COVID-19 in the Netherlands was largely unknown. Recently, hospitalization data from 2024 were made available for the purpose of monitoring and evaluating the COVID-19 vaccination campaigns. These data were linked to the population registry, vaccination registry and healthcare use data (for classification into medical risk groups). We analyzed the number and incidence of COVID-19 hospitalizations in 2023 and 2024 by age and medical risk group. VE against hospitalisation of the autumn booster of 2023 (by time since vaccination, 25 September 2023 to 16 September 2024) and of the autumn booster of 2024 (16 September to 31 December 2024) were estimated by medical risk group among persons aged 60 years and older using Cox proportional hazards models with calendar time as underlying time scale and vaccination status as time-varying exposure. Models were adjusted for age, sex, region and household socio-economic status. From around age 60 onward, intermediate and high medical risk groups had a markedly higher incidence than younger age groups, increasing with age. Persons in the low medical risk group had a low incidence up to the age of 80. In 2024, incidence was lower than in 2023. For both autumn booster rounds, estimated VE against hospitalisation was moderate at 55-67% in the first 3 months post-vaccination. In the high medical risk group, 2023 VE decreased fast and was no longer significant at 6 months post-vaccination. For both years, estimates of the number of averted hospitalizations and number needed to vaccinate to prevent one hospitalization indicated that significant health benefit can be achieved by vaccinating the intermediate and high medical risk groups aged 60 years and older. Efforts to increase the moderate vaccine uptake among risk groups could potentially prevent a considerable disease- and healthcare burden. Highlights- In 2023 and 2024, incidence of COVID-19 hospitalization was highest among medical risk groups aged 60 years and older, despite vaccination campaigns. - Estimated VE against hospitalisation of the 2023 and 2024 autumn booster campaigns was moderate (55-67%) in the first year-quarter post-vaccination among persons aged 60 years and older. - Estimated VE of the 2023 autumn booster decreased over the year, and faster among persons with a medical risk condition. Data availability precluded estimates of 2024 VE beyond the first 3 months since the start of the campaign. - Despite lower and waning VE, the estimated number needed to vaccinate to prevent one COVID-19 hospitalization was much lower among intermediate and high medical risk groups compared with the low medical risk group.

BackgroundSerotype 3 (S3) has remained a major cause of invasive pneumococcal disease (IPD) despite its inclusion in 13-valent pneumococcal conjugate vaccine (PCV). In October 2023, a 15-valent PCV (PCV15) including S3 was introduced into the Catalan universal childhood immunization program. MethodsWe conducted a retrospective pre-post surveillance study to compare pediatric IPD incidence in Catalonia during a pre-PCV15 period (October 1, 2022-September 30, 2023) and two post-PCV15 periods (October 1, 2023-September 30, 2024, and October 1, 2024-September 30, 2025). All IPD episodes in children <18 years attended in 34 hospitals were included. IPD was defined as detection of S. pneumoniae in a sterile site by culture or PCR. Results323 IPD episodes were identified in 319 children (mean age, 4.5 years). Overall IPD incidence declined from 13.0 to 9.4 episodes per 100,000 children in the first post-PCV15 period compared with the pre-PCV15 period (28% reduction; p=0.02), but returned to baseline in the second post-PCV15 period. S3-IPD incidence decreased significantly from 4.1 to 1.6 episodes per 100,000 (60% reduction; p=0.001) in the first post-PCV15 period and remained lower in the second period: 2.3 episodes per 100,000 (42% reduction compared with baseline; p=0.04). In contrast, IPD incidence caused by PCV7 serotypes increased from 0.3 in the pre-PCV15 and first post-PCV15 period to 2.7 episodes per 100,000 in the second post-PCV15 period (690% increase; p<0.001). ConclusionPCV15 introduction was associated with a sustained reduction in S3-IPD over two years. However, a marked increase in PCV7 serotypes offset overall gains in IPD incidence. SUMMARYPCV15 introduction in Catalonia achieved sustained reduction in serotype 3 invasive pneumococcal disease over two years, but a marked increase in PCV7 serotypes offset the overall disease reduction in the second post-vaccination year.

A number of vaccines and long-acting monoclonal antibodies have been shown to be effective in the prevention of respiratory syncytial virus (RSV) disease. However, an immune correlate of protection for RSV has not yet been identified. We conducted a systematic review to identify published reports of immunogenicity and/or efficacy in vaccines and long-acting monoclonal antibodies against RSV and performed a meta-analysis on extracted data to identify any relationship between antibody increase and protection against RSV disease. We identified 130 relevant reports which we classified into an open access evidence map of RSV immunisation products. We found a strong correlation between the immunisation induced rise in neutralising antibody titres and efficacy ({rho}>0.7 for all comparisons, Spearman). For infants, we estimated that each 10-fold increase in neutralising antibody titre rise provides an additional 31% [95% CI 10%-47%], 47% [95% CI 36%-56%] and 57% [95% CI 45%-66%] reduction in the relative risk of symptomatic, moderate and severe disease respectively. For older adults, a 10-fold rise in antibody levels was associated with a 34% [95% CI -2%-57%], 50% [95% CI 22%-67%] and 63% [95% CI 36%-79%] reduction in the relative risk of RSV disease with 1, 2 and 3 symptoms respectively. These results align extremely well with findings from natural history studies and individual-based analysis of correlates of protection studies. This work paves the way for use of neutralising antibodies as a correlate of protection to guide the development, approval, and deployment of RSV vaccines and monoclonal antibodies.

BACKGROUND AND OBJECTIVESSeasonal influenza vaccination has been shown to reduce the risk of influenza and severe complications among children 6 months and older. Since 2010, reported numbers of influenza-associated pediatric deaths among children aged <18 years have ranged from 37 during the 2011-2012 season to 289 during 2024-2025. We estimated influenza vaccine effectiveness (VE) against pediatric death from 2016-2017 through 2024-2025. METHODSWe conducted a case-cohort analysis comparing current season influenza vaccination status among reported influenza-associated pediatric deaths with survey estimates of influenza vaccination coverage in pediatric age groups. Underlying medical conditions and current seasonal influenza vaccination were obtained from surveillance case reports. We estimated vaccination odds ratios (OR) and 95% confidence intervals (CI) from logistic regression comparing influenza vaccination among children who died with vaccination coverage in comparison cohorts. VE was calculated as (1 - OR) x 100. RESULTSFrom August 2016 through July 2025, 1234 laboratory-confirmed influenza-associated pediatric deaths were reported among children aged 6 months--17 years. Of 1086 reported deaths including influenza vaccination information, 124 (23%) of 530 children with underlying medical conditions and 70 (13%) of 556 children without known conditions were fully vaccinated against influenza. Average influenza vaccination coverage in survey cohorts was 49%. VE was 80% (95% CI, 75% to 84%) overall, 77% (95% CI, 71% to 82%) among children with underlying medical conditions and 87% (95% CI, 84% to 89%) among children without known conditions. CONCLUSIONSInfluenza vaccination reduced risk of fatal influenza among children with or without known underlying medical conditions.

BackgroundMeasles is a highly contagious infectious disease and a leading cause of childhood morbidity and mortality worldwide. In developing country like Ethiopia, effective immunization is a proven strategy for reducing measles related illness and deaths. However, measles second dose vaccination drop out has become a major public health concern. In a densely populated city such as Addis Ababa drop rate tends to be higher than the minimum acceptable threshold, leading to increased number of cases and recurrent outbreaks. Despite of this limited evidence exists on the determinants of second dose drop out and the problem is not well investigated, as a result this study will try to identify determinants of measles second dose vaccination dropout among children 24 - 35 months of age. ObjectivesTo identify determinants of measles second dose vaccination dropout among children 24 - 35 months of age Addis Ababa, Ethiopia in 2025. MethodCommunity based unmatched case control study was conducted in Addis Ababa from September 1/2024 to October /2025 with a total of 636 participants, consisting of 212 cases and 424 controls. Data were collected using structured Quesionariie and entered into EpiData 3.1 then StataSE 18 was used for detailed analysis including Descriptive statistics. Model fitness was checked using Hosmer-Lemeshow and multicollinearity were assessed using variance inflation factor. Furthermore, Bivariable and multivariable logistic regression analyses was employed and Adjusted odds ratio with 95% confidence intervals was used to identify significant variables. ResultsA total of 620 mothers/caregivers participants respond to the study, comprising 206 (97%) cases and 414(97.6%) controls, yielding a total response rate of 97.4%. In this study, waiting time longer than 30 minutes (AOR= 3.34, 95%CI: 1.86-5.9), Lack of counseling (AOR = 2.63, 95% CI: 1.60-4.30), Lack of reminders (AOR = 2.86, 95% CI: 1.89-4.30), Previous adverse event following immunization (AOR = 2.00, 95% CI: 1.39-3.00), postnatal care visit (AOR = 0.58, 95% CI: 0.40-0.85) and family size of greater than 3 (AOR = 1.96, 95% CI: 1.29-2.98) were significantly associated with measles second dose dropout. Conclusion and recommendationIn study shows measles second dose dropout is found to be associated with long waiting time, lack of counseling, lack of reminder, history of adverse event following immunization and postnatal visit. Which suggests Strengthening Immunization Counseling, reducing waiting time, establishing effective reminding system, integrating Immunization with postnatal services and promptly addressing concerns about adverse event following immunization can help reduce measles second dose dropout.

BackgroundCervical cancer, generally induced by human papillomavirus (HPV) infection remains one of the most prevalent and deadly female cancers in sub-Saharan Africa (SSA). In Cameroon, the impact of prevention strategies is limited by systemic challenges, and insufficient evidence base to guide effective interventions. This study aimed to synthesize available evidence on the prevalence and key determinants of HPV infection among Cameroonian women. MethodsA comprehensive search was conducted across PubMed, Scopus, Web of Science, Embase, Cochrane electronic databases and local online publishers. Quality assessment of included studies was performed using the Joanna Briggs Institute (JBI) critical appraisal tool. The random effect model was used to pooled the estimates. Heterogeneity was evaluated using the I2 statistics. Statistical significance was set at p <0.05 and all analyses were conducted using R Statistics version 4.5.2. The protocol was registered on PROSPERO (CRD420261279093). ResultsThirty-six studies (20,033 participants) were included. The pooled prevalence of HPV infection 36.10 (95% CI: 27.28-45.97) with high heterogeneity (I2 = 98.4%). Higher estimates were observed among female sex workers 62.10% (95% CI: 58.08-66.00%, 1 study, n = 599) and women with pre-cancerous genital lesions 85.53% (95% CI: 61.72-95.59%, 4 studies, n = 673). Significant determinants of HPV infection included age below 40 (OR = 1.31; 95% CI: 1.14-1.49; 7 reports), unmarried status (OR = 1.43; 95% CI: 1.24-1.64; 15 reports), having five or more sexual partners (OR = 1.26; 95% CI: 1.05-1.51; 2 reports), parity below four (OR = 1.29; 95% CI: 1.09-1.52; 2 reports), HIV infection (OR = 1.92; 95% CI: 1.24-2.98; 6 reports), CD4 count below 500 cells/mm3 (OR = 2.00; 95% CI: 1.02-3.95; 2 reports), and viral load below 1000 copies/mL (OR = 2.12; 95% CI: 1.27-3.53; 2 reports). ConclusionsOur study demonstrates a high and persistent burden of HPV infection in Cameroon, with a greater impact on younger women and women living with HIV. These findings highlight an urgent public health need to strengthen and expand prevention strategies to effectively reduce and eliminate cervical cancer incidence in the country.

BackgroundPreoperative biliary stenting alters biliary colonization and may reduce the effectiveness of perioperative antibiotic prophylaxis in pancreatoduodenectomy. Although broader-spectrum regimens have been associated with improved infectious outcomes, their microbiological adequacy in routine clinical practice remains poorly defined. We therefore evaluated the real-world adequacy of a prolonged ampicillin-sulbactam protocol, its association with infectious outcomes and survival, and the potential impact of a universal piperacillin-tazobactam strategy. MethodsWe analyzed all consecutive patients who underwent elective pancreatoduodenectomy from 2002 to 2023 at our tertiary center. Demographic, operative, microbiological, and outcome data were retrieved from a prospectively maintained database. Patients were stratified by stent status. Adequacy of prophylaxis was defined as the full in vitro susceptibility of all bile isolates. The outcomes included 30-day infectious morbidity, clinically relevant POPF, PPH, DGE, reoperation, 30- and 90-day mortality and long-term survival. A coverage simulation was performed to compare ampicillin-sulbactam with a hypothetical universal piperacillin-tazobactam. Statistical methods included chi-square/Fishers exact tests, Mann-Whitney U tests, Cox models, McNemars test and Poisson regression. ResultsOf 956 patients, 424 (44%) had a biliary stent. Technical complications were comparable between groups, and rates of POPF and PPH were not increased. However, infectious morbidity was higher in stented patients, including sepsis (RR 1.62, 95% CI 1.05-2.51) and postoperative cholangitis (RR 2.20, 95% CI 1.36-3.56). Thirty- and 90-day mortality were increased (RR 2.88 and 2.73) but lost significance after adjustment. Bile cultures predominantly yielded Enterococcus and Enterobacterales with low ampicillin-sulbactam susceptibility. Overall adequacy was 21.7%. Among patients with bile cultures (n = 474), ampicillin-sulbactam covered 43.7% (207/474) versus 81.2% (385/474) with piperacillin-tazobactam; in stented patients with cultures (n = 397), coverage increased from 41.8% to 78.1%. Adequate ampicillin-sulbactam coverage was not associated with reduced infectious outcomes in Poisson models. ConclusionPreoperative stenting creates a polymicrobial, partially resistant biliary niche that ampicillin-sulbactam does not sufficiently cover. Our data shows that a piperacillin-tazobactam strategy substantially improves coverage and was therefore implemented at our center. Core message- Stented patients exhibit a distinct infectious risk profile characterized by Enterococcus-and Enterobacterales-dominated bile colonization rather than increased rates of technical complications. - In stented patients, real-world microbiological coverage of ampicillin-sulbactam was limited, and in vitro susceptibility did not independently translate into reduced postoperative infectious morbidity. - Broader prophylaxis, such as piperacillin/tazobactam, aligns with the actual flora and nearly doubles theoretical coverage, addressing the mismatch between stent-associated biofilms and narrow regimens.

BackgroundZero-dose children, defined as those who have not received a first dose of a diphtheria-pertussis-tetanus (DPT)-containing vaccine, represent one of the sharpest manifestations of inequity in immunisation systems. Nigeria remains one of the largest contributors to the global zero-dose burden, with North-East Nigeria facing intersecting crises of conflict, population displacement, governance fragility, and weakened primary health care. Existing research has largely focused on structural determinants such as poverty, maternal education, and rural residence, with far less attention to relational mechanisms and governance dynamics that shape caregiver decisions. MethodsWe conducted a cross-sectional secondary analysis of the 2023 Nigeria Demographic and Health Survey (NDHS) Childrens Recode dataset. Weighted descriptive statistics and survey-adjusted logistic regression models were used to estimate zero-dose prevalence and identify structural and health system-contact determinants among children aged 12-23 months ResultsThe weighted national zero-dose prevalence was 37.1% (95% CI: 35.2-39.0), meaning more than one in three eligible children had never received a DPT-containing vaccine. The strongest independent predictors of zero-dose status were no ANC visits (aOR = 6.68, 95% CI: 5.52-8.09), no maternal education (aOR = 4.70, 95% CI: 2.89- 7.67), poorest wealth quintile (aOR = 2.79, 95% CI: 1.82-4.27), home delivery (aOR = 1.41, 95% CI: 1.18-1.69), and rural residence (aOR = 1.45, 95% CI: 1.18-1.75). Crude regional disparities were marked but attenuated after adjustment, suggesting that the apparent North-East effect is largely mediated through structural and service-contact pathways. ConclusionZero-dose status in Nigeria reflects deep structural exclusion and fragmented early contact with the health system, rather than isolated individual preferences. ANC utilisation and place of delivery emerge as pivotal touchpoints where health systems can either build or erode trust and continuity of care. These findings provide a quantitative foundation for future research exploring relational and contextual mechanisms shaping immunisation exclusion.

COVID-19 remains a substantial public health challenge in the Netherlands. Next-generation COVID-19 vaccine, mRNA-1283, is approved in the European Union, with potential for higher relative vaccine efficacy compared with originally-licensed COVID-19 vaccines. Its potential public health and economic impact, in adults [&ge;]60 years and high-risk 18-59 years, was modelled versus no vaccination and originally-licensed mRNA-1273 and BNT162b2, adapting a published static Markov model with 1-year time horizon. COVID-19 burden reflected two full post-pandemic seasons. Vaccine efficacy versus mRNA-1273 was based on pivotal phase 3 NextCOVE trial data; efficacy versus BNT162b2 was derived from an indirect treatment comparison. The economically justifiable price (EJP) of mRNA-1283 versus no vaccination, and price premiums over existing vaccines, were determined at a willingness-to-pay threshold of {euro}50,000/quality-adjusted life-year (QALY) gained. Without COVID-19 vaccination, an estimated 460,000 infections, 23,800 hospitalizations and 5,300 deaths would occur. With current coverage, mRNA-1283 was estimated to prevent 68,000 infections, 5,400 hospitalizations, and 1,200 deaths, saving 9,667 QALYs and over {euro}66.5 million in treatment costs. The EJP was {euro}238 versus no vaccination. Compared with mRNA-1273 and BNT162b2, mRNA-1283 was estimated to prevent additional burden (e.g., 1,309 and 1,679 hospitalizations, respectively), and was cost-effective at an incremental EJP of {euro}62 versus mRNA-1273, and {euro}80 versus BNT162b2. The results support continued COVID-19 vaccination to mitigate the ongoing health and societal burden of SARS-CoV-2 in the Netherlands. The comparative analyses indicate that mRNA-1283 may be associated with substantial health benefits over originally-licensed mRNA vaccines; consequently, its use may further improve health outcomes and economic efficiency within COVID-19 vaccination programs.

BackgroundReliable identification of early predictors of adverse outcomes was essential during the pre-vaccination phase of the COVID-19 pandemic. Few studies have comprehensively integrated clinical presentation, laboratory parameters including arterial blood gas analysis, and chest computed tomography (CT) findings within a single well-characterized cohort, particularly in underrepresented regions of Brazil. MethodsThis retrospective cohort study included 482 consecutive adults (median age 61 years [IQR 49-73]; 64.3% men) with RT-PCR-confirmed SARS-CoV-2 infection hospitalized at a tertiary cardiac center in Central-West Brazil between March 2020 and January 2021. Demographic, clinical, laboratory (including arterial blood gas analysis), and chest CT data obtained within 48 hours of admission were analyzed. Univariable logistic regression was performed for 76 variables. Multivariable models were constructed using an a priori variable selection strategy based on clinical relevance, representation of distinct pathophysiological domains, and adherence to events-per-variable principles. Complete-case analyses were performed without imputation. ResultsIn-hospital mortality was 9.3% (45/482). Invasive mechanical ventilation was required in 74 patients (15.4%), with a mortality rate of 58.1% among those ventilated. In univariable analysis, 42 variables were associated with mortality (p < 0.05). In multivariable analysis (n = 438), five independent predictors of death were identified: age (adjusted OR 1.66 per 10 years; 95% CI 1.19-2.32; p = 0.003), arterial pH (adjusted OR 0.47 per 0.1-unit increase; 95% CI 0.25-0.89; p = 0.021), neutrophil-to-lymphocyte ratio (adjusted OR 1.30; 95% CI 1.18-1.44; p < 0.001), number of comorbidities (adjusted OR 1.59; 95% CI 1.25-2.02; p < 0.001), and serum creatinine (adjusted OR 1.37; 95% CI 1.05-1.77; p = 0.019). The model demonstrated good calibration (Hosmer-Lemeshow p > 0.05) and moderate-to-high explanatory power (Nagelkerke R{superscript 2} = 0.43). For the composite outcome of death or invasive mechanical ventilation (74 events; 15.4%), four predictors remained independently associated; serum creatinine showed a non-significant trend (p = 0.069). On chest CT (n = 424), analyzed descriptively and in univariable models only, pulmonary involvement > 50% was associated with increased odds of death (OR 2.87; 95% CI 1.42-5.79; p = 0.003). ConclusionsFive admission variables representing distinct pathophysiological domains--age, arterial pH, neutrophil-to-lymphocyte ratio, comorbidity burden, and serum creatinine--were independently associated with in-hospital mortality in this pre-vaccination cohort. Arterial pH provided independent prognostic information beyond inflammatory and renal markers. These findings support early risk stratification using routinely available clinical data.

Background. Although health mediation is widely studied in the U.S. through community health worker programs, evidence on their effectiveness in promoting cancer screening in Europe is limited. Since 2022, the "13 en Sante" program has implemented a multicomponent health mediation intervention -combining educational activities, outreach strategies, and navigation support- in socioeconomically disadvantaged neighbourhoods of Marseille, France. This study evaluates the effectiveness of this program in promoting breast, colorectal, and cervical cancer screening. Methods. A controlled before-after design based on two cross-sectional surveys was conducted in 2022 and 2024 in intervention or control neighbourhoods. Individuals aged 18-74 were randomly selected and interviewed via door-to-door questionnaires. Weighting was applied to account for stratified sampling and to align age and sex distributions with census data. Weighted logistic regression models were fitted for each cancer screening to estimate the intervention's effects on uptake and awareness at both individual and population levels. Findings. Overall, 4,523 individuals were included across the two cross-sectional surveys. The program successfully reached individuals facing cumulative socioeconomic barriers to healthcare access. No significant population-level effect was observed. At the individual level, declared exposure to health mediation was associated with significantly higher uptakes of breast and colorectal cancer screenings (breast: 54% vs 74%, OR=2.3 [1.1-4.5]; colorectal: 30% vs 50%, OR=2.8 [1.3-5.8]). In addition, colorectal cancer screening awareness was significantly higher among exposed participants (83% vs 93%, OR=8.1 [2.1-31]). Interpretation. This study provides the first evidence that a multicomponent health mediation intervention could effectively promote breast and colorectal cancer screening in disadvantaged French neighbourhoods. The study highlights screening-specific mechanisms of action that should be considered to further optimize intervention effectiveness. Funding. The survey was funded by the Regional Health Agency of Provence-Alpes-Cote d'Azur and Sante publique France.

BackgroundText messages are a low-cost digital health solution that can provide information directly to mothers. We aimed to evaluate a text message program, called Essential Coaching for Every Mother Tanzania (ECEM-TZ), designed to improve maternal access to essential newborn care education during the immediate 6-week postnatal period. MethodsA randomized controlled trial was conducted in Dar es Salaam, Tanzania. ECEM-TZ consists of standardized text messages from birth to 6 weeks postpartum that provided evidence-based information on newborn care and recognizing danger signs. The primary outcome was newborn care knowledge. Secondary outcomes included parenting self-efficacy, breastfeeding self-efficacy, postpartum depression and anxiety symptoms, attendance at the six-week postnatal check-up, and newborn morbidity and mortality. Data were analyzed using ANCOVAs and logistical regression. ResultsBetween June 13 and July 22, 2024, 143 mothers were randomized, 71 to the control group (standard care) and 72 to the intervention group (standard care plus ECEM-TZ), of which 139 completed both the baseline and follow-up at 6-8 weeks postpartum. Compared to the control group, mothers who received ECEM-TZ had significantly higher newborn care knowledge scores (MD=2.92, p<0.001) and fewer postpartum depression symptoms (MD=-1.55, p<0.001). Mothers who received ECEM-TZ were also three times more likely to attend a postnatal visit than those in the control group (OR=3.15, 95%CI [1.29, 7.72]). ConclusionText messaging, as a low-cost, accessible digital health solution, is an important asset to enhance education of mothers in low- and middle-income countries during the immediate 6-week postpartum period. Trial registrationClinicalTrials.gov (NCT05362305), submitted 22-April-2022.

BackgroundHospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP), particularly those caused by multi-drug resistant organisms (MDROs), often require newer antibiotic treatment. The efficacy and safety of newer antibiotics compared to generic antibiotics in randomized controlled trials (RCTs) have not been evaluated before. MethodsIn this systematic review, we searched RCTs in the United States National Library of Medicine (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, Ovid MEDLINE, Clinical Trials.gov and Google Scholar databases published between 2013 and 2025. The primary efficacy endpoint was 28-day all-cause mortality. Secondary efficacy endpoints were clinical and microbiological response. Safety endpoint was nephrotoxicity. ResultsWe identified eight eligible RCTs involving 2,881 patients (1,450 patients treated with newer antibiotics and 1,431 patients treated with generic antibiotics) with HABP/VABP. The meta-analysis did not reveal any significant differences between newer and generic antibiotics for all-cause mortality at day 28 (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.72-1.30), clinical response (RR 1.04, 95%CI 0.93-1.17), and microbiological response (RR 1.05, 95%CI 0.89-1.24). However, newer antibiotics showed significant lower occurrences of nephrotoxicity compared to colistin component (RR 0.30, 95%CI 0.11-0.79). In subgroup analysis, newer antibiotic regimens demonstrated significant improvement in microbiological eradication of carbapenem-resistant Gram-negative bacilli (RR 1.50, 95%CI 1.18-1.90). ConclusionsNewer antibiotics showed similar efficacy and safety in treating HABP/VABP compared to generic drugs. The superiority in microbiological eradication of carbapenem-resistant Gram-negative bacilli of newer antibiotics could suggest that future trials should be targeted for those patients to improve understanding of their therapeutic use and pathophysiology of these conditions. Key pointsNewer antibiotics, despite broader antimicrobial coverage, have not significantly outperformed generic comparators in terms of 28-day all-cause mortality, clinical, or microbiological response in patients with Gram-negative HABP/VABP. This may reflect limitations in current trial designs focused primarily on regulatory approval.

Embedding equity into vaccine eligibility is essential for reducing health inequalities. Yet, adult vaccine eligibility in most European countries is primarily based on fixed age thresholds, prioritising cost-effectiveness. This approach risks excluding the most vulnerable populations living in deprived communities with poorer health and shorter survival into older age. Extending eligibility based on clinical risk partially addresses this gap. Higher rates of underdiagnosis and delayed diagnosis in deprived populations limit the fairness of this approach, however, with the status quo of adult vaccine eligibility criteria likely doing active harm. In this perspective, we demonstrate the extent of this inequity in England. For example, the average male living in Hyde Park in the northern city of Leeds dies 9.5 years too early to ever receive the RSV vaccine offer at age 75. Meanwhile, a male living in Hyde Park, London, lives much longer and may receive the benefits of the RSV vaccine for 10 years or more. Drawing on lessons from the COVID-19 pandemic, we propose further evaluation of alternative eligibility models that incorporate local place-based disadvantage, which will inherently account for life expectancy and deprivation levels. These models will ensure earlier access to vaccines for communities with the greatest need and improve health equity without overwhelming health systems.

IntroductionChildhood immunization is highly cost-effective, yet uptake is shaped by sociocultural and religious influences. In Bauchi State, Nigeria, coverage remains low (Penta3 58.2%; fully vaccinated according to the national schedule 22.5% among children aged 12-23 months; Nigeria Demographic and Health Survey (NDHS) 2024). Religious leaders shape community norms, but their perspectives on immunization in Bauchi are not well characterized. Guided by Omans model of religion/spirituality and health, we explored religious leaders knowledge, beliefs, attitudes, practices and recommendations regarding childhood immunization. MethodsBetween December 2022 and January 2023, semi-structured interviews were conducted with 22 religious leaders purposively sampled across Bauchi State (geographically stratified by local government area). Sampling continued until thematic saturation. Interviews were conducted in Hausa or English, audio-recorded, translated into English where necessary and transcribed. Data were analyzed using Braun and Clarkes thematic analysis in ATLAS.ti. Ethical approval was obtained from the Bauchi State Health Research Ethics Committee, and participants provided verbal informed consent. ResultsMost leaders described immunization as preventive and compatible with religious teachings and reported that observed child health benefits reinforced support. Many described shifts from earlier skepticism to endorsement after lived experience and religious and scientific explanation, while noting persistent misinformation, particularly fertility-related and "population control" narratives. Leaders described three recurring influence practices: Visible role modelling, sermon-based messaging aligned with scripture, and community mobilization through religious gatherings and support during outreach activities. Leaders emphasized that respectful health worker engagement and reliable service delivery were perceived to strengthen trust and support community uptake. ConclusionReligious leaders in Bauchi State may be strategic partners for improving vaccine acceptance. However, this leader-level qualitative study did not measure congregant outcomes. Programs should consider structured engagement with religious leaders, strengthen bidirectional rumor tracking and response, and support frontline health workers to strengthen trust and demand for routine and outreach immunization services, pending evaluation. Future work should include dissenting and more diverse leaders and link engagement to measurable outcomes. SUMMARY BOXO_ST_ABSWhat is already known on this topicC_ST_ABSO_LIChildhood immunization coverage remains low in northern Nigeria, including Bauchi State, and both demand- and supply-side barriers contribute to under-vaccination C_LIO_LIReligious leaders can influence health behaviors and have been engaged in immunization efforts, but their perspectives and practical roles are not consistently described for Bauchi State C_LI What this study addsO_LIMost interviewed religious leaders viewed childhood immunization as preventive and compatible with religious teachings, and many described actively supporting immunization after engagement with immunization programs C_LIO_LILeaders reported persistent community concerns and misinformation, including fertility-related rumors, alongside service delivery constraints such as distance, waiting times, and staff attitudes C_LIO_LILeaders described mobilization practices, including sermon messaging, role modelling, and outreach-related community engagement, and proposed practical program improvements, including house-to-house service delivery and coordination between immunization teams and local religious leaders C_LI How this study might affect research, practice and policyO_LIImmunization programs may benefit from structured partnerships with religious leaders, including timely, credible information and co-developed messaging to address misconceptions C_LIO_LIImprovements in service accessibility and respectful care should accompany demand-generation to maximize impact C_LI

BackgroundRotavirus remains a leading cause of childhood diarrhoeal hospitalisation globally. Malawi introduced the monovalent G1P8 rotavirus vaccine (Rotarix(R)) in October 2012 and in April 2016 switched from trivalent to bivalent oral poliovirus vaccine (tOPV to bOPV). More than a decade after Rotarix(R) introduction, evidence on sustained vaccine effectiveness and population-level impact in high-transmission, low-income settings remains limited, and it is uncertain whether programme changes such as the OPV formulation switch have influenced Rotarix(R) performance over time. MethodsWe estimated the long-term impact and effectiveness of Rotarix(R) on diarrhoea hospitalisation in Malawi and explored whether OPV type changes Rotarix(R) effectiveness. We used interrupted time-series and test-negative case-control analyses to assess the impact and effectiveness of Rotarix(R), respectively, over seven years post vaccine introduction using data from diarrhoeal surveillance studies in children under five years hospitalised with acute gastroenteritis at Queen Elizabeth Central Hospital, in Blantyre, Malawi, between 1997 and 2019. Stool samples from these children were collected and tested for rotavirus A antigen using enzyme immunoassay (EIA). To assess the effect of concurrent vaccination with OPV, we used a test-negative case-control study to estimate the interaction between the two vaccines. FindingsThe interrupted time-series was based on 7,952 hospitalisations and showed a 23% (95% confidence interval (CI): 10 - 34%) reduction in rotavirus hospitalisations rates among children under five years in the post-vaccine introduction period (January 2013 - December 2019) compared with the pre-vaccine period (July 1997 - December 2012). There was a stronger effect among infants under one year (37%; 95% CI: 25 - 47%). Protection declined with age, with little measurable impact beyond infancy. The test-negative analysis enrolled 1,909 children and Rotarix(R) effectiveness for two doses was 52% (95% CI: 18 - 71%) overall, 67% (95% CI: 36 - 82%) among infants and 29% (95% CI: -136 - 74%) in those older than one year. Analyses of the tOPV to bOPV switch (n = 1,622) showed no measurable interaction with Rotarix(R) performance (aOR 1.07; 95% CI: 0.85 - 1.34). InterpretationRotarix(R) provides moderate protection for Malawian infants, and the transition from tOPV to bOPV did not influence vaccine effectiveness. The lower effectiveness of rotavirus vaccination with increasing child age highlights the need to evaluate alternative vaccination strategies alongside strengthened WASH interventions to sustain vaccine impact in LMICs. FundingMRC Discovery Medicine North (DiMeN) Doctoral Training Partnership (UKRI) and National Institute for Health and Care Research (NIHR) Research in contextO_ST_ABSEvidence before this studyC_ST_ABSMultiple reviews have evidenced variable vaccine effectiveness by setting and age. A recent global review and meta-regression of efficacy and effectiveness data by the authors (https://doi.org/10.1016/j.eclinm.2025.103122), updated to October 2024, highlighted lower rotavirus vaccine effectiveness and impact in high-burden, low- and middle-income countries (LMICs) compared with high-income settings. Studies in LMICs including those in sub-Saharan Africa (SSA) consistently indicate that protection is strongest in infants, with impact and effectiveness declining in older children. Multiple factors have been implicated for this variability in effectiveness, including interference from co-administration of oral polio vaccines. We also conducted a systematic review of post-licensure rotavirus vaccine impact and effectiveness studies from sub-Saharan Africa (CRD42023436851). We also assessed the principal study designs used and the extent to which they adjusted for concurrent public health and social measures (PHSMs). We searched PubMed, EMBASE, MEDLINE, CINAHL, and Google Scholar for studies of vaccine impact or effectiveness in children under five years and screened reference lists of included studies. Across all eligible studies, none measured or adjusted for concurrent public health or social measures. To date, most SSA evaluations have focused on the early post-introduction period, with limited evidence on longer-term vaccine performance and no epidemiological evaluation of the potential effect of co-administration of oral polio vaccines on rotavirus vaccine effectiveness. Added value of this studyWe provide a long-term evaluation of the monovalent rotavirus vaccine (Rotarix(R)) in Malawi using a single hospital-based surveillance platform spanning the pre-vaccine and post-vaccine periods. We combine interrupted time-series analyses of population-level impact with test-negative estimates of individual-level effectiveness using consistent age strata. We also examine whether the national switch from trivalent to bivalent oral poliovirus vaccine modified rotavirus vaccine effectiveness, addressing a programme change that has rarely been assessed in rotavirus vaccine evaluations. Implications of all the available evidenceThe available evidence indicates modest rotavirus vaccine benefit in sub-Saharan Africa, with protection concentrated in infancy and little measurable effect in older children. Our findings highlight the need to interpret long-term vaccine impact estimates alongside changes in other PHSMs that influence rotavirus disease burden, including water and sanitation and access to care. The absence of an effect associated with OPV formulation change suggests that modifying OPV valency alone is unlikely to improve rotavirus vaccine performance. Extending protection beyond infancy may require alternative vaccine schedules alongside sustained improvements in broader public health conditions.

BackgroundHigh-dose inactivated influenza vaccination (HD-IIV) demonstrates superior effectiveness versus standard-dose vaccination (SD-IIV) in adults aged [&ge;]60 years. A recent meta-analysis integrated complementary evidence sources of representing over 85 million individuals across 14 influenza seasons. MethodsA previously developed model was updated using life-time horizon and societal perspective. Updated parameters included demographics, costs, hospitalization rates, and relative vaccine effectiveness (rVE): RCT evidence (24% for ILI, 7% for cardiorespiratory hospitalizations) and RCT + real-world evidence (RWE) (15% for ILI, 8% for cardiorespiratory hospitalizations). ResultsHD-IIV resulted in incremental cost-effectiveness ratios of {euro}7,300/QALY (RCT evidence) and {euro}5,800/QALY (RCT+RWE evidence). Implementation would prevent 7,200 general practitioner visits, 6,300 cardiorespiratory hospitalizations, and 269 deaths, by using RCT evidence. Probabilistic sensitivity analysis demonstrated >99% probability of cost-effectiveness at {euro}20,000/QALY threshold for both RCT and RCT+RWE evidence. ConclusionsHD-IIV remains highly cost-effective for Dutch adults aged [&ge;]60 years under updated evidence scenarios, supporting implementation in the national immunization programme. HighlightsO_LIThe economic analysis of high-dose inactivated influenza vaccine was updated. C_LIO_LIRelative vaccine effectiveness of HD-IIV incorporating recent evidence was used. C_LIO_LIHD-IIV remains cost-effective in Dutch adults aged [&ge;]60. C_LI

BackgroundThere is a need for synthetic peptide-based serologic assays that exploit avidity to replace whole antigens while enabling low-cost diagnostics in resource-limited settings. ObjectiveTo evaluate the diagnostic accuracy of a polymeric peptide-based ELISA leveraging avidity to enhance signal. MethodA 15-member SARS-CoV-2 peptide library corresponding to multiple epitope clusters and proteins was screened by indirect ELISA using pooled sera from RT-PCR-confirmed COVID-19 patients to identify peptides with possible diagnostic utility. The identified lead candidate, S559, possessed terminal cysteine-substitution to allow disulfide polymerization, and the resulting avidity gain was evaluated by comparing the apparent dissociation constant (KDapp) before and after depolymerization with N-acetylcysteine. The performance of an optimized ELISA using S559 was evaluated on 1,222 prospectively collected COVID-19 serum samples and 218 biobanked pre-COVID control serum samples. ResultsPolymeric S559 with a KDapp of 29.26 nM-1was demonstrated to have a 218% avidity gain relative to the completely depolymerized form. At pre-defined thresholds, the optimized S559 ELISA has a sensitivity and specificity of 83.39% (95%CI: 81.18% and 85.43%) and 96.79% (95%CI: 93.50% and 98.70%), respectively. At post hoc thresholds determined by Youden index, sensitivity and specificity reached 95.01 (95% CI: 93.63% - 96.16%) and 100.00% (95% CI: 98.32% - 100.00%), respectively. ConclusionHomomultivalent epitope presentation using polymeric S559 allows a highly specific immunoassay using human sera that may have important value in detecting antibodies, whether for diagnosing infection, confirming vaccination status or conducting surveillance.