Vaccine: X

Background: Incomplete childhood vaccination undermines individual and herd immunity and increases vulnerability to vaccine-preventable diseases. Understanding local determinants of vaccination adherence is essential for targeted interventions. This study assessed routine immunization completion and dropout patterns among children aged 0-15 months in Bayelsa State, Nigeria. Objectives: To determine vaccination completion rates, identify factors influencing adherence, analyze temporal patterns across immunization milestones, and provide evidence-based recommendations for improving coverage. Methods: A comparative longitudinal study was conducted from March 2023 to July 2024 across three Local Government Areas (LGAs), representing each senatorial district. A total of 369 mother-child pairs (123 per LGA) were enrolled. Data were obtained from health facility immunization registers and supplemented with semi-structured questionnaires. Children were followed through the 6th week, 10th week, 14th week, 9th month, and 15th month immunization visits. Completion rates were analyzed using descriptive statistics and chi-square tests. Ethical approval was obtained from the State Ministry of Health, and informed consent was obtained from all mothers. Results: Completion rates varied across LGAs, with the highest in LGA C (86.2%) and lowest in LGA B (61.0%). Phone-based reminders achieved the highest adherence, outperforming routine and home visit strategies. Progressive attrition was observed along the immunization schedule, with dropout exceeding completion by the 15th month. Principal reasons for non-completion included forgetfulness, travel, and caregiver busyness. Maternal age, education, and occupation significantly influenced adherence, indicating disparities across LGAs. Conclusion: Vaccination adherence is shaped by maternal characteristics and operational strategies. While early-stage coverage is high, attrition increases at later milestones, particularly in LGAs with lower resource engagement. Recommendations: Implement targeted phone-based reminders, milestone-specific outreach, and community engagement programs to reduce dropout, enhance timely completion, and strengthen childhood immunity.

Background and Objectives: SARS-CoV-2 (COVID-19) continues to mutate, circulate, and adversely impact health and quality of life. While COVID-19 vaccines remain safe and effective, uptake remains low, especially among children, the youngest of whom were not vaccine-eligible until after Omicron and are underrepresented in published research. This study estimated vaccine effectiveness (VE) among under-5-year-olds. Methods: We used Virginia Department of Health surveillance data from June 2022 through October 2022 to conduct a test negative case-control study. We estimated VE derived from odds ratios (ORs) of reported infections using logistic regression among children aged 6-months to 5-years. Results: Using the earliest positive (cases) or negative (controls) post-vaccine-eligible test results, the VE associated with two doses of a COVID-19 vaccine was 78% (95% CI=45%, 93%; p=0.004) in unadjusted analyses and 70% (95% CI=25%, 91%, p=0.023) when adjusting for age, sex, prior testing behavior, and prior reported infections. The adjusted VE was 74% (95% CI=28%, 94%; p=0.025) among those with no prior positives reported and 45% (95% CI=-302%, 97%; p=0.569) among those with a prior positive reported. Conclusions: These results show that even though the vaccine was not closely matched to the dominant variants circulating during the time period analyzed, it was effective at reducing the risk of reported infections. This study adds to the body of knowledge on pediatric COVID-19 VE in an underrepresented age-group and in a rural region, illustrates the utility of surveillance data for evaluation, and can inform vaccine decisions to improve vaccine uptake for young children.

Adenoviruses (Ads) are widely used as vaccine vectors. However, pre-existing immunity to commonly used serotypes, like Ad5, can reduce vaccine immunogenicity, with neutralizing antibody titers >200 previously shown to impact vaccine efficacy. Gorilla adenovirus (GRAd) vectors have been developed to evade pre-existing anti-vector responses, but their seroprevalence in southern Africa is poorly defined. Here, we assessed seroprevalence to GRAd32, Ad26 and Ad5 before (baseline) and after COVID-19 vaccination, in cohorts from South Africa and Zimbabwe. Sera from South African participants enrolled in the Sisonke sub-study (n=100, prior to Ad26.COV2.S vaccination) and the follow-up "Booster after Sisonke" (BaSiS) study (n=226) were tested for neutralizing antibodies to Ad5, Ad26, and GRAd32. These samples included paired pre/post boost samples for 27 donors. We also tested sera from the Zimbabwean Mutala cohort (n=131, of which 44 were unvaccinated, and 87 vaccinated with inactivated vaccines). Participants living with HIV (PLWH) comprised 30-50% of each cohort. In the pre-vaccination samples from the Sisonke cohort, geometric mean titers (GMT) for anti-GRAd32, Ad26, and Ad5 antibodies were 78, 142, and 459, with neutralization titers >200 observed in 14%, 32%, and 68% of participants, respectively. Similarly, in the unvaccinated participants in the Mutala cohort, GMTs for GRAd32, Ad26, and Ad5 were 117, 245, and 536, with neutralizing titers >200 in 22%, 42%, and 69% of participants. We observed no significant difference in Ad antibody titers between PLWH and those living without HIV. We next assessed the impact of COVID-19 vaccination on titers. Vaccination with inactivated COVID-19 vaccines (Sinopharm/Sinovac) did not significantly affect Ad5, Ad26 or GRAd32 titers in an unpaired analysis. In contrast, [~]9 months after Ad26.COV2.S vaccination, anti-Ad26 titers for longitudinally sampled participants (n=27) increased 10-fold from a GMT of 141 to 1,426. By comparison, GRAd32 responses were not significantly altered by Ad26.COV2.S vaccination, while anti-Ad5 responses showed a modest <2-fold increase. Our data support previous findings that, whereas anti-Ad5 neutralizing antibody responses are commonly detected globally, GRAd32 responses are less frequent. Importantly, GRAd32 neutralizing responses remained unchanged after Ad26.COV2.S vaccination. HIV status had no significant effect on antibody titers. These results support the use of the GRAd32 vector in upcoming HIV vaccine trials, including in regions where Ad26-based COVID-19 vaccines were widely deployed.

Background Pediatric immunizations for Respiratory Syncytial Virus (RSV), including monoclonal antibodies for infants and vaccines for pregnant people, have become broadly available and can prevent severe RSV outcomes in infants. However, quantifying the impact of RSV immunization in prevention of severe pediatric illness at the population-level is limited by lack of RSV case surveillance data. The Massachusetts Department of Public Health (DPH) conducted a modeling analysis using routine public health surveillance data to estimate the state-level impact of new RSV immunization products on Emergency Department (ED) visits and hospitalizations in Massachusetts for highest risk pediatric groups. Methods A scenario projection tool, called R.Scenario.Vax, was utilized to simulate RSV-associated ED hospital encounters by age group in the context of newly available immunizations. ED visit and hospitalization data from the National Syndromic Surveillance Program (NSSP) during the time period 10/08/2017--10/19/2024 were analyzed, scaled to account for changes in RSV testing practices over time and missing encounter volume in historic data, and utilized to inform model fit of a "typical" RSV season. RSV immunization data from the Massachusetts Immunization Information System (MIIS) for the 2023--2024 and 2024--2025 RSV seasons informed high and moderate pediatric RSV immunization coverage scenarios and their impact was compared to a counterfactual reference scenario of no new immunizations. Median projections were quantitatively and qualitatively compared to observed 2024--2025 season data. Percent reduction in hospital encounters and encounters averted per 10,000 population were calculated for each scenario as compared to the reference. Results Projections for the youngest at-risk age groups showed significantly lower RSV-associated ED visits and hospitalizations during the 2024--2025 season for both high and moderate immunization coverage scenarios. Median projections for infants under 6 months old in the highest coverage scenario, wherein nearly all infants were immunized, showed 72.6% lower ED visits and 73.4% lower hospitalizations when compared to the reference scenario, equating to 262 ED visits and 85 hospitalizations averted per 10,000 population. Conclusions Our results support the use of modeling methods for public health insights and suggest that RSV immunizations for infant populations result in significantly lower RSV-related ED encounters in Massachusetts.

Suboptimal rotavirus vaccine effectiveness in low- and middle-income countries (LMICs) highlights the need for next-generation vaccines, such as the neonatal RV3-BB vaccine. However, there is uncertainty in the duration of protection and future price of vaccines in development. We aim to identify the conditions under which switching to RV3-BB is optimal in Malawi and Ghana, where the current immunization programs use 2-dose Rotarix and 3-dose Rotavac schedules, respectively. A full incremental cost-effectiveness analysis was performed using a validated transmission model calibrated to country-specific rotavirus data. Over 2025-2034, introducing RV3-BB resulted in the largest rotavirus-related burden reduction compared with the current country-specific programs. At moderate willingness-to-pay (~0.5 time Gross Domestic Product per capita), RV3-BB was preferred over Rotavac if price per dose was <$1.2 in Malawi and <$2.5 in Ghana, and/or if the average duration of protection exceeded 40 weeks in Malawi. The RV3-BB vaccine is likely to be cost-effective in Malawi and Ghana, as well as other LMICs, based on expected pricing and duration of protection.

Background: Tanzania introduced the human papillomavirus (HPV) vaccine in 2018 for girls aged 9-14 years; however, coverage remains suboptimal. Missed opportunities (MOs) for vaccination are an important but understudied barrier, particularly in urban settings. This study assessed factors associated with MOs and explored healthcare providers perspectives on barriers and potential solutions in Dar es Salaam. Methods: An embedded mixed-methods study was conducted in public health facilities in Temeke Municipal Council from June - July 2025. The quantitative component involved a cross-sectional survey of 252 parents or caregivers of eligible adolescent girls using structured exit interviews. The qualitative component included in-depth interviews with 20 healthcare providers using a phenomenological approach. Multivariable logistic regression identified factors associated with MOs. Qualitative data were analyzed thematically using Braun and Clarkes framework. Results: The prevalence of MOs for HPV vaccination was 71.4%. Factors independently associated with MOs included caregiver age [&ge;]40 years (aOR 1.87, 95% CI: 1.02-3.42), female caregiver gender (aOR 1.61, 95% CI: 1.00-2.59), primary education (aOR 2.14, 95% CI: 1.03-4.45), married status (aOR 1.72, 95% CI: 1.01-2.94), and receiving care at health centers or dispensaries versus hospitals (aOR 1.83, 95% CI: 1.05-3.19). Qualitative findings identified key drivers of MOs, including limited caregiver knowledge, vaccine hesitancy, time constraints, failure to routinely offer vaccination, stock-outs, poor documentation, high workload, and limited outreach. Proposed strategies included routine eligibility screening, reminder systems, community engagement, and supportive supervision. Conclusion: MOs for HPV vaccination are highly prevalent and driven by both caregiver and health system factors. Strengthening routine screening, reminder systems, community engagement, and supervision may improve vaccine uptake.

Aims: COVID-19 and influenza continue to impose a substantial burden on the Canadian healthcare system, particularly among adults aged greater than 65 years. This study compared the clinical and economic outcomes of a Stand-alone vaccination strategy with separate influenza and COVID-19 vaccines versus a Combination strategy incorporating mRNA-1083, an investigational vaccine targeting both infections. Methods: The study adopted the public healthcare payer perspective and adapted a previously published static model to predict COVID-19 and influenza infections across a one-year time horizon. Relative vaccine effectiveness (rVE) for mRNA-1083 against COVID-19 compared with the stand-alone vaccine (SPIKEVAX) was based on the pivotal clinical trial of mRNA-1083s COVID-19 component (mRNA-1283). For influenza, no incremental VE was assumed versus the adjuvanted stand-alone vaccine (FLUAD). Infections were modeled independently. Clinical outcomes included symptomatic infections, hospitalizations, and deaths. The economically justifiable price (EJP) was calculated at the willingness-to-pay (WTP) threshold of $50,000 per quality-adjusted life-year (QALY) gained. mRNA-1083 uptake was assumed to yield absolute increases in COVID-19 and influenza coverage by 10% and 3%, respectively. Results: Compared with the Stand-alone strategy, the Combination strategy was projected to reduce the number of COVID-19-related symptomatic infections, hospitalizations, and deaths (n=71,074; 5,008; 935, respectively), and corresponding influenza outcomes (n=3,985; 362; 69, respectively). The use of mRNA-1083 within the Combination strategy generated a cost-savings of $90,440,471 in vaccine administration fees and an EJP of $304 per dose. Results were sensitive to rVE, coverage, administration fees, mortality and incidence. Limitations: mRNA-1083s rVE is being evaluated in clinical trials and the impact of mRNA-1083 on vaccine coverage and administration fees is uncertain. Conclusions: mRNA-1083 may reduce the burden of COVID-19 and influenza in adults aged greater than 65 years in Canada, while offering good economic value because it has the potential to increase coverage and VE while reducing administration fees.

Background Robust quantitative evidence on the impact of rotavirus vaccines, their potential benefits in countries without vaccination, and strategies to improve performance in low- and middle-income countries (LMICs) is essential for informing policy decisions aimed at sustaining and expanding vaccination programs. Methods and Findings We used an age-structured compartmental model of rotavirus gastroenteritis (RVGE) transmission that accounts for the natural history of infection to estimate vaccine impact across 112 LMICs. The model incorporates country-specific data on demographics, transmission dynamics, vaccination schedules, coverage levels, and vaccine performance. We simulated multiple scenarios, including the continuation of current vaccination programs, vaccine introduction in countries without programs, the addition of a third dose, scale-up of coverage to 95% in low-coverage settings, and suspension of vaccination. We quantified health impacts by estimating cases, deaths, and disability-adjusted life years (DALYs) averted from 2006 to 2024 and projected over 2025 to 2034 using either no vaccination or the current program as counterfactual. We estimated that rotavirus vaccination averted a median of 268 million RVGE cases (95% uncertainty interval [UI]: 228-306 million), 35 million moderate-to-severe cases (95% UI: 30-38 million), 817 thousand deaths (95% UI: 684-928 thousand), and 53 million DALYs (95% UI: 45-61 million) between 2006 and 2024, resulting from 81 countries with vaccination programs out of 112 LMICs. Using the current vaccination as a baseline, we estimated substantial additional benefits for all strategies, except for suspension, which would increase the RVGE burden over the next 10 years. Scaling up coverage to at least 95% across all 112 LMICs, with countries without the vaccine using the 6/10/14-week schedule, could avert a median of 296 million RVGE cases (95% UI: 243-358 million), 832 thousand deaths (95% UI: 694-932 thousand), and 55 million DALYs (95% UI: 45-61 million), respectively. Furthermore, adding a third dose in the 51 countries currently using a two-dose schedule could enhance vaccine impact, averting a median of 123 million RVGE cases (95% UI: 102-145 million), 377 thousand deaths (95% UI: 310-440 thousand), and 24 million DALYs (95% UI: 20-28 million), respectively, compared to the two-dose schedule. Conclusions Our model demonstrates that rotavirus vaccination provides substantial health benefits, with an even greater impact achievable through broader adoption and increased coverage. Adding a third dose to the standard two-dose Rotarix schedule could be an additional strategy to improve vaccine impact in LMICs. These findings support continued efforts to sustain and expand vaccination programs across LMICs. The country-specific, model-estimated rotavirus burden can also inform economic evaluations to guide more effective vaccination strategies.

Background Despite the significant impact of longstanding paediatric pneumococcal conjugate vaccine (PCV) use in the United Kingdom (UK), pneumococcal disease burden remains substantial and is primarily driven by nonPCV13 serotypes. Higher valent vaccines such as the 20 valent PCV (PCV20) may provide additional public health and economic benefits, yet their value in the contemporary UK setting has not been fully assessed using recent data. Methods We updated an age structured dynamic transmission model using post COVID 19 UK epidemiology (2001 to 2023) to compare pediatric PCV20 with PCV13 and PCV15. Over a 10 year horizon, we assessed cost effectiveness and number needed to vaccinate (NNV), capturing invasive and non invasive disease cases, deaths, costs, quality adjusted life years, and incremental cost effectiveness ratios. PCV20 was evaluated under 1+1 and 2+1 schedules; PCV13 and PCV15 were assessed under 1+1. Scenario analyses examined key uncertainties. Results PCV20 was estimated to avert more cases and deaths than PCV13 or PCV15, driven by broader serotype coverage and indirect effects. Both PCV20 schedules were dominant or cost saving versus lower valent comparators, with lower NNVs. PCV20s higher vaccination costs were offset by reductions in downstream healthcare expenditures. Conclusion Paediatric PCV20 implementation in the UK could deliver substantial health gains while improving economic efficiency, supporting timely adoption.

Despite concerns about the spread and pandemic potential of H5N1, there is no commercial H5N1 vaccine. Seasonal influenza vaccines offer some cross-protection against H5N1, but to date there has been no consideration of whether protection differs between the sexes. We investigated immune responses and protection in adult male and female C57BL/6 mice following vaccination with either inactivated H1N1 or H5N1 (LAIV backbone) virus vaccines. Vaccination induced strong homologous antibody responses, with females generating greater total IgG than males against both H1N1 and H5N1 vaccine, which was primarily mediated by greater IgG responses to neuraminidase (NA) than hemagglutinin (HA) protein. IgG cross-recognition of H1N1 also was greater among H5N1 vaccinated females and was primarily caused by greater IgG responses to N1. IgG2b and IgG2c were the primary isotypes generated in response to these vaccines, with females having greater IgG2b responses and greater binding to Fc{gamma}RIV for avian and human NA than males in response to both homologous and heterologous vaccination. Antibody-dependent complement deposition was measured as an FcR-mediated non-neutralizing response against HA and NA and was robust in both sexes. Vaccinated females had greater neutralizing antibody titers than males against the homologous vaccine virus, with limited cross-neutralizing antibodies detected in either sexes. Neuraminidase inhibition titers were greater in vaccinated females than males against the heterologous virus following H1N1 vaccination and against both the vaccine and heterologous viruses following H5N1 vaccination. When H1N1 and H5N1 vaccinated mice were challenged with a lethal dose of A/Texas/37/2024 H5N1, all H5N1 vaccinated mice were protected, regardless of sex. Among H1N1 vaccinated mice, while both sexes were protected against disease, H1N1 vaccinated females cleared virus faster than their male counterparts. These findings highlight that female-biased NA-specific antibodies result in greater cross-protection and should be considered in studies of influenza vaccines. HighlightsO_LIFemales mount stronger IgG responses than males to both H1N1 and H5N1 vaccines C_LIO_LISex differences in vaccine responses are driven by immunity to neuraminidase (NA) C_LIO_LINA inhibition titers are greater in females, supporting broader cross-protection C_LIO_LIH5N1 vaccination confers full protection in both sexes against lethal H5N1 challenge C_LIO_LIH1N1-vaccinated females clear H5N1virus faster than males after lethal challenge C_LI

Breast cancer was the leading cause of cancer-related mortality among women worldwide in 2022. In Kenya, more than a quarter of breast cancer patients have the aggressive Human Epidermal Growth Factor Receptor 2 positive subtype. Trastuzumab is recommended for its treatment, but high costs have limited access. This study evaluated the cost-effectiveness and affordability of trastuzumab-based regimens to inform their adoption and use in Kenya. A cost-utility analysis was conducted from the healthcare payer perspective over a lifetime horizon. Five trastuzumab-based regimens of varying durations (9-week, 6-month, 9-month, 12-month, and 24-month) were compared with chemotherapy alone. Direct medical costs were estimated using a bottom-up micro-ingredient approach. All costs were reported in 2022 USD. A cohort Markov state-transition model with a monthly cycle length was used to estimate the costs and outcomes for an open hypothetical cohort. Scenario, deterministic sensitivity and probabilistic sensitivity analyses were conducted. A budget impact analysis estimated the financial implications of each regimen. The 9-week regimen had the lowest incremental cost-effectiveness ratio (ICER) of USD 3,230 per QALY, while the remaining regimens had ICERs ranging from USD 4,046 to 9,846 per QALY. The findings were most sensitive to the price and quantity utilized per cycle of trastuzumab. A reimbursement cap of KES 40,000 per cycle reduced ICERs by up to 61%. Over five years, the 9-week regimen would account for 1.2% of the projected insurers budget, whereas the current recommended 12-month regimen would consume 2.82%. Although none of the regimens were cost-effective at Kenyas WTP threshold (USD 1054.80), the 9-week regimen may still be considered by policymakers given its greater affordability. Further cost reductions can be achieved through negotiating lower drug prices, improving access to biosimilars, and implementing vial sharing.

Objectives In Quebec, Canada, vaccination against human papillomavirus (HPV) has been publicly-funded since January 2016 for gay, bisexual, and other men who have sex with men (GBM) aged [&le;]26 years. The study aimed to analyze data collected in Greater Montreal (Engage study) to evaluate the HPV vaccination program for GBM in Quebec. Study Design Engage is a cohort of sexually active GBM aged [&ge;]16 recruited via respondent-driven-sampling (RDS) in Canada. Participants completed a questionnaire and tested for sexually transmitted infections. Methods RDS-II weights were applied to adjust for recruitment. Subgroups were compared using standardized mean differences. Odds ratios of HPV vaccination and prevalence ratios of anal HPV infection adjusted for potential confounders were estimated using robust regression models. Results Of 1179 participants, 309 were eligible for free HPV vaccination. Vaccine coverage among eligible GBM was 42%. Among those who disclosed same-sex sexual activity and discussed HPV vaccination with their healthcare provider, coverage reached 82%. Anal HPV prevalence among eligible GBM was 26.5% for [&ge;]1 HPV-6/11/16/18 genotypes without significant difference between vaccinated and unvaccinated individuals. Among unvaccinated GBM aged [&le;]26 who were aware of the vaccine, 60% intended to get vaccinated within the next year. Conclusions One to two years after GBM aged [&le;]26 were included in the Quebec HPV vaccination program, 42% of eligible GBM in Greater Montreal had been vaccinated. Anal HPV prevalence was high among GBM. Vaccinees were more likely to self-report a prior STI diagnosis. Offering vaccination to all preadolescents in schools appears essential to maximize vaccination benefits.

Background: Vaccination coverage estimates and case-based surveillance have limitations in evaluating immunization programs. Serosurveillance offers a complementary approach by directly measuring population immunity. We assessed whether serologic analyses across multiple antigens (i.e., measles, diphtheria, tetanus) could provide additional insights into vaccination program performance. Methods: We conducted a matched case-control study among children aged 2- to 10-years-old (n=1286) in Zambia using specimens from the 2016 ZAMPHIA survey. Using previously generated data on measles serostatus, measles seronegative children (i.e., cases) were matched to measles seropositive children (i.e., controls) on sex, age, HIV infection status, and province. Samples were tested for tetanus and diphtheria antitoxin IgG antibodies using commercial enzyme immunoassays. We estimated the odds of tetanus and diphtheria seropositivity by measles serostatus using conditional logistic regression and examined age-specific antibody dynamics. Results: Measles seronegative children had 1.7-fold increased odds (95% credible interval [CrI]: 1.3-2.1) of being tetanus seronegative compared to measles seropositive children. Diphtheria serostatus had no significant association with measles serostatus (odds ratio: 1.3; 95% CrI: 0.9-1.7). Tetanus seroprevalence declined monotonically with age. However, diphtheria seroprevalence initially declined through 5 years of age, then increased again beginning at 6 years of age despite the lack of vaccine booster doses given after the primary series in infancy, potentially from asymptomatic or subclinical infections. Conclusions: Serologic analyses revealed measles serostatus was positively associated with tetanus serostatus (where seropositivity arises only via vaccination and not infection), suggesting children who are measles seronegative are more likely to have missed DTP vaccination. We additionally found that measles serostatus was not associated with diphtheria serostatus, suggesting that antibody responses to diphtheria continue to boost beyond infancy when DTP vaccination is given. Our findings support consideration of DTP booster doses in Zambia to address waning tetanus immunity and further investigation of potential diphtheria carriage and transmission.

Background: The Vaccine Safety Datalink (VSD) detected a statistical signal for ischemic events (ischemic stroke or transient ischemic attack) following bivalent mRNA COVID-19 vaccination through prospective surveillance during 2022-2023. Although multiple studies from other surveillance systems and countries reported no increased risk, important methodological limitations remained. This U.S. study addressed those limitations by evaluating the ischemic stroke risk following bivalent mRNA COVID-19 vaccination, influenza vaccination, and their same-day coadministration using event-dependent self-controlled case series (SCCS) design. Methods: Study outcomes included first-ever ischemic stroke (primary outcome), first-in-1-year ischemic stroke (secondary outcome), and ischemic events (exploratory outcomes), identified using ICD-10-CM codes in inpatient and emergency department settings during September 1, 2022-March 31, 2023, among individuals aged>=12 years across eight VSD sites. Analyses were conducted separately for Pfizer-BioNTech and Moderna bivalent vaccines, with relative incidences (RI) and 95% confidence intervals (CI) estimated for 1-21-day and 1-42-day risk intervals, using person-time outside these intervals as the control period. Subgroup analyses were performed by age group (12-64, >65 years) and history of documented SARS-CoV-2 infection. Results: A total of 6,510 first-ever ischemic strokes were identified among more than 6.8 million participants. Among recipients of Pfizer-BioNTech bivalent COVID-19 and influenza vaccines, no statistically significant increased risk of first-ever ischemic stroke was observed following bivalent COVID-19 vaccination (RI=0.94; 95% CI: 0.63-1.41), influenza vaccination (RI=0.95; 95% CI: 0.82-1.10), or same-day coadministration (RI=1.15; 95% CI: 0.88-1.49) within 1-21-day risk intervals; findings were similar for 1-42-day intervals. Comparable null results were observed for Moderna vaccines and across all subgroups, secondary, and exploratory outcomes. Conclusion: No increased risk of ischemic stroke was found following bivalent mRNA COVID-19 vaccination, influenza vaccination, or their coadministration in this multi-site SCCS study. These findings are consistent with previous studies and underscore the importance of continued vaccine safety monitoring.

Introduction-India's immunization initiatives are among the largest globally, characterized by a substantial birth cohort of 27 million children annually, and have achieved significant progress in increasing coverage through the UIP. However, there are still challenges that persist, and multiple determinants contribute to the existing challenges; parental migration is one of them. Migration has always been a key driver of socio-economic and demographic changes, particularly in low and middle-income countries (LMICs). Specifically, there is a need to better understand the vulnerabilities of immunization among recent migrants. To examine this, the study explores the association between a mother's recent migration and the full immunization coverage of children aged 12-23 months in India. Data & Methods-Our study utilized data from the National Family Health Survey-5 (2019-21). The outcome variable of interest in this study is the receipt of all basic vaccinations (full immunization) for children. The primary predictor variable in this study is the children's migration status. We used a series of multivariate logistic regression models to examine the relationship between full Immunization and recent migration of children, with some data restrictions in the models. Results - The results show a 17% difference in full immunization between migrant and non-migrant children. The odds ratios for children who had recently migrated were lower for full immunization (OR: 0.39, 95% CI: 0.35-0.43) compared to children who had not recently migrated. Even across the household wealth quintile and social groups, the recent migration of children was associated with being less likely to be fully immunized among children 12-23 months. Conclusion- The findings of this study provide significant quantitative evidence that recent migration (less than 3 years) of children is a key factor influencing Immunization coverage and is a predictor of full vaccination among children aged 12-23 months in India. The recent migration was consistently linked to a lower likelihood of full immunization coverage across different household wealth levels and social groups. This study suggests that recently migrated children are a vulnerable subgroup of the population at risk of not receiving all basic vaccinations by their first birthday.

Introduction: Respiratory infections are a leading cause of morbidity. Newly available vaccines to prevent respiratory syncytial virus (RSV) disease and encouraging clinical progress on vaccines for human metapneumovirus (hMPV) and parainfluenza (PIV) could reduce the disease burden beyond existing influenza and SARS-CoV-2 immunisation programs. However, evidence on the contribution of these viruses to respiratory disease burden across the lifespan remains limited. Methods: We reviewed studies from 01/2002-11/2025 reporting age-stratified, medically attended cases of influenza, and at least one of RSV, hMPV, or PIV, in high-income countries, excluding periods substantially overlapping with the COVID-19 pandemic. Using only studies that tested for all four viruses, we estimated the age-specific proportion of cases that were non-influenza (total across RSV, hMPV and PIV) compared to influenza using a mixed-effects logistic regression model. Results: Following exclusions and screening, 61 studies were included in the primary analysis comprising >500,000 detections of the four viruses. We found that a substantial proportion of medically attended respiratory illness in infants and young children was due to PIV, hMPV and RSV, rather than influenza, with a non-influenza virus proportion of 90.2% (95% CI 85.9-93.2%) in young infants aged 0-6 months. The converse was true for school-aged children, with a non-influenza virus proportion of 34.8% (95% CI 26.5-44.2%) in children aged 5-18 years. In adults aged 65+ years, non-influenza causes of medically attended disease were common at 60.2% (95% CI 50.0-69.5%). Restricting to studies reporting hospitalised cases (n=19) produced broadly similar age-specific trends in relative virus burden contributions. Discussion: We highlight the significant burden of medically attended illness due to PIV, hMPV and RSV across ages, particularly in infant and preschool-aged children and older adults, supporting the need for effective vaccines targeting this burden.

Background: Diarrheal illness in children leads to 3.5 million care visits and 200,000 hospitalizations annually in the US. Viruses are responsible for most pediatric diarrheal cases, yet limited guidance on distinguishing viral from bacterial etiologies complicates clinical decision-making, especially regarding empiric antibiotic use. Methods: We used clinical and qualitative molecular etiologic data from the Implementation of Molecular Diagnostics for Pediatric Acute Gastroenteritis (IMPACT) study to develop prediction models for viral etiology of diarrhea. We used conditional random forests to identify informative clinical and environmental predictors and evaluated model performance using logistic regression and random forests within a 5-fold cross-validation framework. We conducted external validation using the Alberta Provincial Pediatric Enteric Infection Team (APPETITE) dataset. Results: Variables predictive of viral etiology included younger age, non-bloody diarrhea, winter season, and presence of vomiting. External validation showed that an AUC of 0.82 can be achieved with a parsimonious 5-variable model, yielding a sensitivity of 0.92 and specificity of 0.55 Conclusion: Our results suggest that in North American healthcare settings, clinical prediction models can inform decision-making by identifying children with a high probability of viral diarrhea, improving diagnostic clarity, and reducing unnecessary testing and treatment.

Of the two influenza A virus (IAV) subtypes circulating endemically in humans, A/H3N2 and A/H1N1pdm09, A/H3N2 has historically been the dominant driver of disease burden in older adults. Based on an analysis of publicly available global surveillance data from 2015 to 2025 (>300,000 subtyped, age-stratified infections), we report a substantially increased contribution of A/H1N1pdm09 to influenza morbidity in older adults since approximately 2022. Birth cohort-stratified analyses suggest elevated A/H1N1pdm09 burden among individuals born before 1955-1959, consistent with erosion of pre-existing immunity originally generated by exposure to historical A/H1N1 strains. Pooled estimates across datasets and analytical approaches indicate the increase in A/H1N1pdm09 burden rises with earlier birth year, ranging from 1.22-fold (95% CI 1.08-1.37) for the 1955-1959 birth cohort to 3.10-fold (95% CI 2.58-3.72) for the 1930-1934 cohort. These findings point to a substantial rise in the overall influenza burden among the most vulnerable age groups, with implications for vaccine policy, clinical management, and public health planning.

Human adenovirus serotype 4 (Ad4) is used as a replication-competent oral vaccine that safely and effectively prevents Ad4 respiratory illness in US military personnel. Recombinant Ad4 vaccine candidates elicit mucosal and systemic immune responses against respiratory viruses in hamsters, nonhuman primates, and humans. Although evaluation of Ad4 vaccine candidates in mice would be extremely useful given the large number of immunologic tools available, this has been limited by concerns about a lack of viral replication in these animals. Here we generated recombinant Ad4 vectors that express either luciferase (Ad4-Luc) or herpes simplex virus type 2 (HSV-2) glycoprotein D (Ad4-gD2) to identify transgene expression kinetics, the presence of Ad4 vector replication, and HSV-2 immune responses and protection against HSV-2 infection. Local luciferase activity was observed from 7 hours to 20 days after intranasal inoculation of BALB/c and humanized mice. Subsequent inoculations with Ad4-Luc showed reduced luciferase expression in BALB/c mice, but robust expression in humanized mice, suggesting an immune response to the vector in wild-type mice. Ad4 DNA, but not luciferase activity, was reduced in the lungs of BALB/c mice treated with cidofovir before inoculation with Ad4, implying that Ad4 replicated, albeit at a low level, in the lungs. Intranasal vaccination of mice with Ad4-gD2 resulted in HSV-2 neutralizing antibody in the serum, and after HSV-2 intravaginal challenge reduced disease scores, increased survival, and reduced shedding. Overall, the BALB/c mouse model is semi-permissive to Ad4 mucosal infection, but transgene expression is sufficient for the study of Ad4-based vaccine candidates. ImportanceMucosal surfaces serve as the primary site of infection and shedding for many viral pathogens. Immune responses at mucosal sites provide protection, but few mucosal vaccines are licensed. The oral replication-competent adenovirus serotype 4 (Ad4) vaccine is used to prevent respiratory illness in military recruits, has an extraordinary record of safety and efficacy and has been tested as a recombinant platform for other viruses. Further development of this vaccine platform has been partially hindered by the perceived inability to evaluate vaccine candidates in mice. Here we characterize recombinant Ad4 transgene expression kinetics and viral replication after inoculation at various sites and show protection against herpes simplex virus type 2 (HSV-2) genital disease in mice after intranasal vaccination. We show that Ad4 can induce protective efficacy, even in a semi-permissive mouse model, suggesting this is a promising vector for HSV-2 and potentially other viral pathogens.

Abstract Objective To Estimate cost of integrating HBV, HCV, and HIV screening at Antenatal using Time-Driven Activity Based Costing (TDACB) Approach; A providers perspective comparing Intervention and standard of care at lower health facilities in West Nile sub region, Uganda Methods Design The Time Driven Activity-Based Costing (TDABC) approach was used to capture resource use and costs associated with delivering integrated HBV, HCV, and HIV screening among pregnant women. This study compared screening uptake among study participants in the intervention, and control group respectively. Five lower health facilities in Koboko and Maracha districts respectively in West Nile region of Uganda. A total of 1,338 study participants wo were pregnant mothers in first ANC, first trimester at the selected 10 facilities were enrolled in this study. Data were abstracted, and also collected on; Personnel/staff time; facility space utilisation; and Medical and non-medical equipment. Total cost per patient visit=Staff time costs+Space cost Equipment cost. Outcome Measure was the estimated provider-perspective costs of delivering integrated screening for HBV, HCV and HIV, using Integrated Care Model by comparing intervention and control groups. Results Staff CCRs demonstrated considerable variability across cadres and facilities, with an overall mean of USD 0.492 per minute (Range: USD 0.167 - 1.318). Laboratory technicians exhibited the highest mean CCR at USD 0.767 per minute for personnel CCRs per patient visit. the mean lowest CPP visit was noted for HBV in the intervention arm (USD 11.43) while HIV test was the lowest in the control arm (USD 0.43). HCV test had the highest cost in the control arm (USD 0.52). The CPP visit for positive clients were generally higher than those that were negative. Equipment CCRs were minimal and highly consistent across facilities, with a mean of USD 0.00069 per minute ({+/-}0.0002). HIV/Syphilis combo was the costliest test kits at USD 3.14 per test kit followed by viral hepatitis C test kit and Hep B at USD 2.47 and USD 0.28 respectively. Facility space CCRs exhibited moderate variation across facilities, ranging from USD 0.01593 to USD 0.03474 per minute. Overall mean CCR for the space for delivering HBV, HCV or HIV testing was USD 0.0256 (0.0066). Conclusion; Overall, the integration of screening resulted in: Cost efficiencies where the same staff and space were used for multiple simultaneous tests, reduced marginal costs for HIV tests due to larger procurement volumes, and higher marginal cost additions for HBV and HCV due to pricier reagents.