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.

Aim: To explore RSV knowledge and awareness, RSV vaccination perceptions and acceptability, and preferences for maternal vaccine delivery and communication amongst pregnant women and mothers of infants and toddlers in England. Methods: Between July and November 2024, semi-structured qualitative interviews were performed with 30 mothers (youngest child under 2 years), two of whom were pregnant with a subsequent child. The study was conducted as a follow-on to a UK Health Security Agency survey of attitudes towards RSV vaccination amongst pregnant and post-partum women in England. Findings: Although most mothers had heard of RSV, mothers with experience in health roles were more likely to understand the potential severity of RSV in infants. Likelihood of maternal RSV acceptance was reported as high, with most mothers considering RSV vaccination as beneficial in protecting infants. Most mothers preferred a hybrid approach to vaccine communication, with information available online (e.g. through the NHS website), via written sources (e.g. NHS produced leaflet), and through talking with midwives. For convenience, most mothers preferred the option of fitting vaccinations within the antenatal midwifery appointment schedule rather than going to general practice for a separate appointment. Conclusion: To support maternal RSV vaccination decision-making and access, women need vaccine information early in pregnancy; information provision through a range of different sources (i.e. online, paper, in-person); and vaccination delivery in a convenient location (i.e. as part of antenatal appointments).

ObjectiveThis study aimed to assess the effectiveness of SMS and voice message reminders in reducing the dropout rate in Lome-Togo, in 2026. MethodsWe conducted a cross-sectional study between October 2025 and March 2026 in the Grand Lome region. The intervention consisted of an integrated digital system used by health facilities to send automated SMS. Categorical variables were described in terms of frequency and proportion; Fishers exact test was used to compare proportions. Quantitative variables were described by their means accompanied by their standard deviation; the Wilcoxon rank-sum test was used to compare means. The significance level for statistical tests was set at 5%. ResultsA total of 30 health facilities were included. Seventy percent (70.0%) of the health facilities used messages associated with calls. Ninety percent (90.0%) of participants found the reminders useful, and 60.0% reported an improvement in Expanded Program on Immunization services related to their use. Among participants who received a reminder, 51.0% kept their vaccination appointments. The Penta 1/3 dropout rate decreased from 3.2% before the intervention to 1.3% (p < 0.001). Among the 323 parents of children included, only 20.74% reported receiving a reminder by phone. Sixty-point-five percent (60.5%) preferred to receive both text messages and voice calls. ConclusionThis study demonstrates the operational feasibility of an SMS/call-based reminder system in reducing dropout rate for childhood vaccination in Togo.

BackgroundAchieving the 2030 target of 90% human papillomavirus (HPV) vaccination coverage among girls by age 15 requires effectively reaching out-of-school (OOS) girls, particularly in low- and middle-income countries (LMICs) where most vaccine delivery occurs in school settings. This study explored how diverse countries define OOS girls and strategies for estimating the size of this population. MethodsBetween May and September 2024, we conducted semi-structured in-depth interviews with 32 HPV vaccine program stakeholders across six African and Asian LMICs with established HPV vaccination programs: Cambodia, Cameroon, Kenya, Malawi, Mozambique, and Uganda. Using hybrid inductive-deductive thematic analyses, we examined how countries taxonomize OOS girls as well as current practices for enumerating or estimating population sizes. ResultsCountries commonly defined OOS girls as those not enrolled in schools under the Ministry of Educations purview, but in practice, this definition varied across contexts. National-level data (e.g., census, school enrollment rates) and household-level approaches (e.g., headcounts) were commonly used to enumerate in-school and OOS girls. However, the distinction between in-school and OOS girls was often blurred during HPV vaccination implementation and evaluation, limiting the operational utility of these methods. To address these challenges, some countries adopted alternative approaches, including proxy-based population estimates using historical or approximate data and the prioritization or areas perceived to have a higher presence of OOS girls. These alternative approaches were perceived as pragmatic compromises between accuracy, feasibility, and resource constraints. ConclusionAccurate enumeration of OOS girls is important for HPV vaccination but may not be feasible in resource-limited settings. Pragmatic, context-specific estimation methods can offer a feasible way to identify and reach OOS girls more effectively with HPV vaccination services.

BackgroundPost-market vaccine safety surveillance and research are essential to detect and evaluate rare adverse events following immunization (AEFIs) not identified in pre-licensure clinical trials, such as myocarditis post-COVID-19 vaccination. AEFI surveillance infrastructure varies between jurisdictions. Factors that enable or hinder AEFI investigation across diverse settings are not well understood. ObjectiveTo examine clinical, social, and structural/system factors that enable AEFI case identification, reporting, data and biosample collection in high-income countries (HICs) and low-and middle-income countries (LMICs). MethodsWe conducted a qualitative study informed by Interpretive Description in Kenya, South Africa, and Canada. Participants were recruited using purposive and snowball sampling from three groups: (1) key informants with leadership roles in AEFI surveillance and research, (2) healthcare workers, research and laboratory staff involved in AEFI investigation and research, and (3) past participants in vaccine studies. Data were collected through semi-structured interviews and focus group discussions. Thematic analysis was conducted. ResultsEighteen key informants, 47 healthcare workers and research staff, and 27 past research participants were enrolled. Facilitators and barriers were identified across two domains: AEFI surveillance and investigation, and vaccine safety research participation. AEFI surveillance and investigation were shaped by trust in system responsiveness, beliefs and awareness around AEFI reporting, digital innovation, and implementation gaps. Research participation was shaped by altruism and social influence, logistics and research infrastructure, and institutional policies and privacy. Facilitators to AEFI surveillance and research included established policies and procedures for AEFI surveillance, digital tools, emphatic communication, and convenient research processes. Barriers included limitations in workforce capacity, diagnostic testing and funding (especially in LMICs), and cumbersome research approval processes. ConclusionsFindings underscore the need for both globally harmonized standards and locally tailored strategies to support vaccine safety surveillance and research in LMICs and HICs that are patient/participant-centered and include sustainable investments in infrastructure and workforce capacity.

Influenza A virus can cause severe complications in pregnant women and infants, yet no influenza vaccines are approved for infants younger than six months. To address this, novel maternal vaccination strategies are needed to increase global access and coverage in these vulnerable populations. This study evaluated a hemagglutinin (HA) A/California/2009 (H1N1)-based human adenovirus 5 (huAd5) vector vaccine, adjuvanted with a TLR3 agonist, for its ability to induce influenza-specific passive immunity from pregnant and lactating pigs to their piglets following different immunization routes. Influenza naive pregnant dams were vaccinated via oral, intranasal (IN), or intramuscular (IM) routes three weeks prepartum and boosted four weeks later. Serum, colostrum and milk samples were collected longitudinally to assess HA-specific antibody induced by vaccination. H1N1-Ca/09 neutralizing antibodies were evaluated in serum and IFN{gamma} producing cells were assessed in blood, spleen and lymph node cells. IN and IM routes elicited robust serum HA-specific antibody responses when compared to control animals at one- and four-weeks post-boost, whereas the oral route resulted in poor antibody induction across all samples tested. Piglets nursing from IN and IM vaccinated dams showed a significantly higher level of HA-specific antibodies in serum at 2-3 weeks post-partum compared to control piglets. Notably, IN immunized dams and their piglets showed significantly elevated influenza neutralizing antibodies compared to controls. This work demonstrated that both IN and IM immunization with a huAd5-vectored vaccine robustly induced maternal influenza-specific immunity that supported passive transfer to nursing piglets, with IN immunization resulting in superior transfer of neutralizing antibodies.

Protracted conflict in Sudan since April 2023 has severely disrupted routine immunization services, particularly in the Darfur region, resulting in widespread vaccine stockouts, declining coverage, and increased risk of vaccine-preventable disease outbreaks. Traditional national supply routes became largely inaccessible, exacerbating inequities in immunization access for conflict-affected and displaced populations. This paper examines the design, implementation, and outcomes of a cross-border vaccine deployment strategy implemented in 2025 through Chad to restore vaccine availability in Darfur. Using programmatic data, shipment records, coverage reports, and partner monitoring outputs, the study assessed the operational feasibility, partnership arrangements, and public health impact of the intervention on routine immunization and outbreak response. In 2025, nearly 20 million doses of vaccines were successfully delivered to the five Darfur states through cross-border operations, supporting routine immunization services and outbreak response campaigns. Average coverage for the first dose of a DPT-containing vaccine (DPT1) increased from 22.6% in 2024 to 83.2% in 2025, while DPT3 and MCV1 coverage rose to 55.4% and 50.4%, respectively. Oral cholera vaccine campaigns achieved 90.4% coverage among targeted populations, and polio outbreak response campaigns exceeded 100% administrative coverage, reflecting both successful reach and uncertainties in target population estimates due to population displacement. Investments in cold chain infrastructure and strengthened coordination among government, UNICEF, Gavi, and implementing partners were critical to these outcomes. The findings demonstrate that cross-border vaccine deployment can serve as a viable and effective mechanism for restoring immunization availability and support recovery of immunization service delivery in a highly constrained conflict setting. While not a substitute for functional national systems, such approaches are essential life-saving interventions during acute crises and should be integrated into preparedness planning for fragile and conflict-affected contexts.

Dengue disease remains a significant global health threat, with current vaccines exhibiting variable efficacy and safety concerns. Virus-like particles (VLPs) offer a promising alternative by mimicking native virus structures without infectious genomes. We engineered a mammalian expression plasmid encoding Dengue-1 prM and E proteins, optimized for secretion using Japanese Encephalitis virus signal sequences, and transiently expressed it in HeLa cells. Purified VLPs exhibited spherical morphology ([~]39 nm diameter) consistent with native virions, as confirmed by transmission electron microscopy. Immunization of mice with these VLPs elicited robust Dengue-1 specific IgG antibody responses. Our study demonstrates production of immunogenic Dengue-1 VLPs in HeLa cells, highlighting their potential as a vaccine candidate and a tool for serodiagnosis. Further characterization of VLP epitopes and protective efficacy is warranted to advance vaccine development. ImportanceDengue remains a significant global health challenge, with serotype 1 being one of the dominant strains causing recurrent outbreaks in Nepal. Existing vaccines demonstrate limited efficacy and pose significant safety concerns, particularly in seronegative populations. To address these limitations, this study explores virus-like particles (VLPs) as a safer alternative vaccine platform. VLPs elicit robust immunogenicity by mimicking the structure of native virus while completely lacking genetic components. This study combines DENV1 structural proteins with optimized expression systems to enhance immunogenicity. This work is particularly significant as the first dengue vaccine research conducted in Nepal, directly addressing antigenic mismatches between existing commercial vaccines and locally circulating viral strains. Furthermore, the study provides scalable platform for developing region-specific dengue vaccines for other serotypes and flaviviruses.

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.

IntroductionCommunity engagement is increasingly seen as essential within vaccination programming to improve uptake of vaccines, build trust and foster community ownership. Yet the goals and mechanisms of such interventions are often contested or not explicit. This article aims to address this by examining how those directly involved in implementing community engagement understand its intended aims and outcomes. We use as a case study a risk communication and community engagement (RCCE) intervention implemented by the Nigeria and Ethiopia Red Cross/Red Crescent with support from the IFRC for COVID-19 vaccination. MethodsWe conducted 41 interviews, 12 participatory workshops and citizen ethnography in Dire Dawa, Ethiopia and Kano, Nigeria including with Red Cross/Red Crescent and vaccination staff, vaccine users and community members. We explored how participants understood the RCCE interventions theory of change, including how it was expected to work, for whom, under what circumstances, and why. ResultsParticipants described RCCE activities as a mix of two-way (such as house-to-house visits) and mass approaches (such as media campaigns). These interventions were primarily seen as enhancing vaccine knowledge and countering misinformation. Key mechanisms included vaccine users willingness to act on the information provided, however this was heavily influenced by the credibility and trustworthiness of the bearers of vaccine information. While feedback mechanisms existed, communities were not involved in designing vaccination strategies. Efforts were shaped by a context with unpredictable vaccination campaigns, supply constraints and parallel RCCE efforts by community actors. ConclusionsWe show that in this theory of change messengers are more influential than the messages themselves. By developing a theory of change with our participants, we highlight the lack of clarity within the sector regarding the definition and expected impact of community engagement and reveal a gap between community engagement practice on the ground and normative goals such as co-production and dialogue. Key messagesO_ST_ABSWhat is already known on this topicC_ST_ABSRisk communication and community engagement (RCCE) is widely used to improve vaccination programmes, but there is limited evidence on how such interventions are expected to work, for whom, under what circumstances and why. What this study addsWe examined how those involved in implementing a Red Cross/Red Crescent and IFRC RCCE intervention in Ethiopia and Nigeria understood the aims and outcomes of this intervention. Whilst our study participants believed their main goal was to share correct vaccine information to counter rumours, we found that trust in the people who delivered the information was often more important than the information delivery itself. How this study might affect research, practice or policyOur research highlights tension between normative ideals of community engagement and how it is understood and practiced by implementors in humanitarian contexts, and underscores the need to move beyond knowledge-deficit approaches.

BackgroundIn Burkina Faso, typhoid fever remains a major public health concern, with a high incidence among children younger than 15 years of age. To address this burden, the country introduced typhoid conjugate vaccine in January 2025 through a national vaccination campaign reaching children aged 9 months to 14 years. This study aimed to estimate the cost of typhoid conjugate vaccine delivery during the national campaign and to identify the main cost drivers across different administrative levels. MethodsWe conducted a cross-sectional, retrospective costing study using a microcosting approach from the government perspective. We collected data from fifty health facilities, eight health districts, five health regions, and the national level. Financial and economic costs were estimated for each level, excluding vaccine and syringe costs. All costs were converted to 2024 USD using the official exchange rate. FindingsVaccinators administered a total of 10.5 million typhoid conjugate vaccine doses. The average financial cost per dose was $0.47 (95% CI: $0.39-$0.51), and the economic cost was $2.16 (95% CI: $1.71-$2.56). Human resources and per diem payments were the main contributors to costs. Costs varied by geography, delivery strategy, and security context, with higher costs observed in rural and conflict-affected areas. The mobile-temporary posts strategy had the highest economic cost per dose ($2.02; 95% CI: $1.64-$2.40), while the fixed strategy had the highest financial cost per dose ($0.41; 95% CI: ($0.32-$0.49). ConclusionThe financial cost per dose remained within Gavi, the Vaccine Alliances operational support range. The observed cost variations highlight the need for targeted funding and enhanced logistical support to ensure equitable access, particularly in rural and insecure areas. This study provides evidence to inform future vaccination campaigns and supports decision-making for typhoid conjugate vaccine introduction in other countries in the region.

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.

BackgroundThe COVID-19 pandemic disrupted childhood immunization programmes in many countries worldwide. However, evidence on its impact in low and middle-income countries remains limited. This study examined the impact of the COVID-19 pandemic on childhood immunization coverage across 514 districts in Indonesia and identified district-level associated factors. MethodsWe conducted a nationwide longitudinal analysis of the Expanded Programme on Immunization to compare immunization coverage before and after the pandemic. The outcome variable was the annual childhood immunization coverage (proportion of children aged 0-12 months who have received all recommended doses of childhood immunization as per the national immunization schedule). The explanatory variables include COVID-19 burden and vaccination rates, health system and human development indicators. Mixed-effect logistic regression was done to assess association between the explanatory and outcome variables. ResultsAt the national level, the coverage was 83.2% in pre-pandemic, 75.0% in the first year of pandemic, and 88.6%, in the second. In the first year, 69.3% of districts experienced significant decline, with a lower national coverage ratio of 0.92 (95% confidence interval 0.89-0.94). In the second year, 36.2% districts were still affected. The multivariable analysis showed that a significant decline in coverage during the first pandemic year was associated with high COVID-19 incidence (adjusted odds ratio 2.19, 95%CI 1.01-4.73 for the highest vs. lowest group), low midwife adequacy (5.84, 2.40-14.16 for the lowest vs. the highest group, 2.61, 1.26-5.40 for low-middle vs. the highest group), and a high proportion of health facility-based births (2.98, 1.49-5.98 for middle-high vs. the lowest group). ConclusionsThe COVID-19 pandemic negatively and unevenly impacted childhood immunization in Indonesia, with greatest impacts in districts facing a higher COVID-19 burden and weaker health system capacity. These findings underscore the need for targeted efforts to strengthen the local health system for future health crises. Summary boxO_ST_ABSWhat is already known on this topicC_ST_ABSO_LIAccording to the WHO Pulse Survey, routine immunizations were the most disrupted essential health services during the COVID-19 pandemic, reported by 70% of countries. Southeast Asia experienced the steepest drop in childhood immunization coverage compared to the other regions. C_LIO_LIIndonesia had the highest number of COVID-19 cases and related mortality in Southeast Asia. However, the magnitude and heterogeneity of the impact of COVID-19 pandemic on childhood immunization coverage across all 514 districts in Indonesia has not been evaluated. C_LI What this study addsO_LIThis study affirmed that the COVID-19 pandemic greatly impacted childhood immunization coverage, disproportionately impacting district with vulnerable health systems capacity. C_LI How this study might affect research, practice, or policyO_LIThis study highlights the critical need of addressing health inequity to strengthen health system resilience for future global health crises. C_LIO_LIIn the context of a decentralised health system such as in Indonesia, coordination and prioritisation of available resources and public health intervention will be critical to ensure optimal health outcomes for children living in districts with weak health systems. C_LI

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.

BackgroundReliable estimates of immunization delivery costs are essential for planning, budgeting, and economic evaluation of vaccination programs. Although a number of empirical costing studies have been conducted in recent years, many low- and middle-income countries (LMICs) continue to lack up-to-date, accurate delivery unit cost estimates--particularly for adolescent and campaign vaccination strategies. Building on prior work, this study aimed to produce updated, standardized country-level estimates of immunization delivery unit costs for different vaccination modalities across all LMICs. MethodsUsing data on study-level unit cost estimates reported by empirical costing studies in the 2024 update of the Immunization Delivery Cost Catalogue, we fitted Bayesian meta-regression models predicting per-dose delivery costs for routine childhood vaccination, routine adolescent vaccination (using human papillomavirus vaccination as a proxy), and vaccination delivered via mass campaigns. Regression models incorporated country-level covariates (per-capita gross domestic product, population size, third-dose diphtheria-tetanus-pertussis vaccination coverage, urbanization, population density, and under-five mortality) and study-level characteristics (cost category, financial versus economic costing perspective, and full versus incremental costing methodology). Fitted models were used to generate country-specific and population-weighted average economic and financial cost per dose estimates for 2024, in 2024 US dollars. ResultsThe analysis included 142 observations for routine childhood vaccination, 63 observations for routine adolescent vaccination, and 113 observations for campaign vaccination. For 2024, the population-weighted mean economic cost per dose across all LMICs was estimated at $5.86 (95% uncertainty interval: $2.74-13.43) for routine childhood vaccination, $17.65 ($7.76-44.30) for routine adolescent vaccination, and $3.13 ($2.03-4.78) for campaign vaccination. Corresponding financial costs per dose were $3.02 ($1.52-6.29), $10.08 ($4.15-25.01), and $1.79 ($1.11-2.91), respectively. Substantial heterogeneity in delivery costs was observed across countries, delivery modalities, and cost perspectives. The estimated associations between predictors and unit costs may be influenced by unobserved study characteristics, and therefore should be interpreted as correlational rather than causal. ConclusionsBy leveraging an expanded empirical evidence base and a Bayesian meta-regression framework, this study provides updated per-dose delivery costs for routine childhood vaccination and estimates new per-dose delivery costs for routine adolescent vaccination and campaign vaccination. As policy decisions often must be made despite incomplete information, these estimates provide a practical source of evidence to support analyses when direct cost data are unavailable.

Background: The value proposition for Shigella vaccines is strengthened by the potential for vaccines to prevent linear growth faltering. However, because expected effect sizes in Phase 3 vaccine trials are small due to limited Shigella incidence, a simple comparison of growth by randomized vaccine arm is likely underpowered and may yield null or even inverse results. Methods: We consider a new approach that estimates vaccine effects in the subgroup that would be infected in absence of vaccination, termed the naturally infected. In simulations parameterized by multi-site studies of diarrhea, we compare power for detecting linear growth effects in the naturally infected versus the full study. We further quantified how power is impacted by trial design choices including immunization schedule, study site, and timing of growth measurements. Findings: Simple comparisons of height-for-age z-score (HAZ) by randomized vaccine arm have extremely limited power (<15%) at realistic trial sizes (n=2,500 to 20,000) and carry risk of showing an inverse effect due to random chance. In contrast, naturally infected effects were five to ten times larger and power was up to three times higher. Using a twelve month immunization schedule with a single growth endpoint in high-incidence settings maximized power to detect an effect. Interpretations: While realistically sized clinical trials may be underpowered to detect an effect of vaccination on growth, estimation using the naturally infected subpopulation and careful trial design improve chances of detecting an effect while mitigating risks of null or inverse results.

BackgroundVaccine-preventable diseases (VPDs) continue to impose a significant health and economic burden globally, despite advances in immunization programs. Narrower to the context of Saudi Arabia, the current literature consistently shows that the high vaccination coverage has had the primary impact of reducing disease incidence. Regardless, the broader economic impact of VPDs and the financial benefits of immunization remain important for policy evaluation within Saudi Arabia. MethodsThis study employed a model-based economic evaluation using a societal perspective in order to carry out an estimation of the economic burden of measles, influenza, and pneumococcal diseases. We utilized the Cost of Illness (COI) approach for the purpose of quantifying direct medical costs and indirect productivity losses. On the other hand, the Value of Statistical Life (VSL) approach helped in the estimation of the monetary value of mortality reduction. A comparative framework analyzed current vaccination coverage against a counterfactual no-vaccination scenario for the calculation of the return on investment (ROI). ResultsThe estimated annual economic burden of the three selected VPDs in the absence of vaccination was USD 385 (95% CI: 315-460) million. Immunization programs generated substantial economic benefits, with total benefits estimated at USD 1085 (95% CI: 815-1360) million annually. The calculated ROI was 9.0 (95% CI: 6.8-11.3), essentially an indication that for each dollar invested in vaccination, there was multiple economic returns yielded. Sensitivity analyses confirmed the robustness of these findings. ConclusionImmunization programs in Saudi Arabia provide significant economic and public health benefits and for this reason, sustained investment in vaccination is fundamentally essential towards the reduction of disease burden, improve population health, and ultimately support long-term economic productivity.

Cameroon introduced Human papilloma virus vaccine (HPVV) into the routine immunization schedule in October 2020. By the end of 2022, coverage remained low. To increase coverage, Cameroon switched to a country-wide, gender-neutral vaccination (GNV) approach in 2023, coupled with a revamped delivery strategy consisting of Community Dialogues (CDs) and Periodic Intensification of Routine Immunization (PIRIs) activities in selected health districts (HDs). We assessed the impact of these programmatic changes, notably the GNV approach, on HPVV coverage. This retrospective, cross-sectional study measured the effect of GNV and CDs + PIRIs on HPVV coverage among 9-year-old girls in Cameroon (2022-2023). Data on HPVV coverage from all 203 HDs were extracted from DHIS2, and coverage was calculated at the HD level, based on the estimated population eligible of 9-year-old girls. Descriptive statistics and multiple regression models were employed to assess the impact of GNV on vaccination coverage while adjusting for CDs + PIRIs and urban/rural status. In 2023, of the 203 HDs, 115 (56.7%) conducted GNV only, 74 (36.5%) implemented GNV & CDs + PIRIs, and 75.9% (154) were classified as rural. Among age-eligible girls, there was an overall increase in HPV vaccination coverage, with coverage rising 39.2 percentage points from 2022 to 2023. Following multiple linear regression, there was a significant increase in HPVV coverage in HDs with GNV & CDs + PIRIs compared to those with no GNV and no CDs + PIRIs ({beta}:55.5%, 95%CI: 38.7, 72.3, p=0.000). Furthermore, there was a significant increase in HPVV coverage in HDs with GNV only compared to those with no GNV or no CDs + PIRIs ({beta}:28.7%, 95%CI: 12.5, 45.0 p=0.001). Overall, the GNV approach increased HPVV coverage for girls significantly, particularly when implemented alongside CDs + PIRIs.