Vaccine: X

Background: In 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. Methods: We 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. Findings: Vaccinators 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). Conclusion: The financial cost per dose remained within Gavi, the Vaccine Alliance's 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.

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.

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: The 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. Methods: We 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. Results: At 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). Conclusions: The 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. Keywords: COVID-19, pandemic, immunization, vaccine preventable diseases

Background Vaccine-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. Methods This 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). Results The 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. Conclusion Immunization 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.

Background Ever since the COVID-19 vaccine became available, vaccinations in adolescents lagged behind adults. Whether adolescent vaccination rates were higher in states with "Minor Consent" policies remains unknown. Methods We accessed adolescent (aged 12-17) county-level vaccine administration data from the CDC (12/2020-05/2023). Our outcomes were COVID-19 vaccination counts for: 1) initial dose, 2) completed series doses, and 3) booster doses. Panel Poisson regression models with state and time random effects, seasonal fixed effects, log-population offsets, and adult vaccination rates were estimated to calculate incidence rate ratios (IRR), testing the association between residing in a state with a Minor Consent policy and COVID-19 vaccine uptake. Results Overall, for the initial dose and complete series, there was no difference in adolescent COVID-19 vaccination between states with or without Minor Consent policies. However, we found that Minor Consent policies were associated with lower COVID-19 booster doses (IRR = 0.582; 95% CI: 0.409, 0.828; p = 0.0026). This association was not found in urban counties (IRR = 0.867; CI = 0.722, 1.043; p = 0.1295), but only in rural counties (IRR = 0.541; CI = 0.401, 0.730; p < 0.0001). Conclusions Minor Consent policies were not associated with higher adolescent COVID-19 vaccination. Rather, we found that Minor Consent policies were associated with lower adolescent vaccination for booster doses in rural counties. Despite minimal evidence of impact, states continue to implement Minor Consent vaccination policies. Future research should investigate not just other vaccines, but also how Minor Consent policies impact parental trust in public health more broadly.

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.

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.

Background To anticipate the impact of new pneumococcal vaccines and guide future updates, accurate forecasts of changes in non-vaccine serotypes (NVTs) are needed. We developed and evaluated three models that incorporated different assumptions about the way in which NVTs will increase and generated ensemble predictions for the frequency of NVTs in different post- pneumococcal conjugate vaccines (PCV) periods. Methods We analyzed age- and serotype-specific invasive pneumococcal disease (IPD) cases from the United States CDCs Active Bacterial Core surveillance during the pre-PCV (1998-1999), early post-PCV7 (2000-2004), late post-PCV7/pre-PCV13 (2005-2009), early post-PCV13 (2010-2014), and late post-PCV13 (2015-2019) periods. These data were augmented with IPD cases from several countries and combined with serotype-specific invasiveness to infer serotype-specific carriage prevalence. Three models (Ranking, Proportionate, NFDS-lite) generated independent predictions of post-PCV IPD frequencies, which were integrated using an accuracy-weighted ensemble. Model performance was evaluated using the normalized root mean square error (NRMSE). Results A total of 23,959 non-PCV7 and 15,580 non-PCV13 cases were analyzed. NVT cases increased from the pre-PCV7 to the late post-PCV7 and post-PCV13 periods. The accuracy of predictions across age groups and models was consistent and high during the post-PCV13 periods but varied during the post-PCV7 periods. The Proportionate model (NRMSE=0.70-3.95) outperformed the NFDS-lite (NRMSE=0.93-8.91) and Ranking (NRMSE=1.51-5.37) models during the early-post-PCV7 period, whereas the NFDS-lite model (NRMSE=1.55-9.82) was superior to the Proportionate (NRMSE=1.45-10.22) and Ranking (NRMSE=1.86-11.35) models during the late post-PCV7 period. The Ensemble model improved on these individual models. Conclusions The Ensemble model offers a tool for forecasting serotype patterns to inform pneumococcal vaccines impact and future pneumococcal vaccine formulation.

Background Catch-up vaccination will be pivotal for achieving WHOs cervical cancer elimination goals in low- and middle-income countries (LMICs). We assessed the health-economic impact of catch-up HPV vaccination for females in LMICs. Methods Using IARCs METHIS modelling platform and data from 132 LMICs, we simulated HPV catch-up vaccination beyond the primary target age, varying the maximum age up to 30 years. Budget impact was expressed as a share of national five-year immunization budgets and current health expenditure. We conducted cost-effectiveness analyses for a smaller subset of countries for which high-quality cervical cancer treatment costs were available. Findings Catch-up HPV vaccination up to age 30 in LMICs could prevent 9.2 million cervical cancer cases over the lifetime among females aged 9-30 years. Across countries, budget impact ranged from 0.007%-2.24% of five-year health expenditure and 0.002%-236.65% of immunization budgets, with vaccine procurement comprising about 70% of costs. Gavi support could reduce costs by nearly 70% for catch-up up to age 18. Catch-up vaccination up to age 30 was cost-effective in almost all evaluated countries, except in one where cost-effectiveness was achieved up to age 21. Interpretation In LMICs, after achieving adequate coverage in the primary target group (9-14 years), expanding HPV catch-up vaccination would be impactful and cost-effective. Sustainable financing, Gavi support, and cost-minimization strategies are crucial for successful catch-up programmes and progress toward cervical cancer elimination.

ABSTRACT Background: Malaria remains a leading public health burden in sub-Saharan Africa, disproportionately affecting children under five years. In response, Kenya introduced the RTS,S/AS01 malaria vaccine in selected regions, including Siaya County where malaria transmission is endemic. Despite this milestone, uptake has been inconsistent, with hesitancy emerging as a significant barrier. Objective: This study aimed to determine factors associated with malaria vaccine hesitancy among caregivers of children 6-59 months in Ugenya Subcounty, Siaya County. Methodology: A cross-sectional mixed methods design was employed involving 425 caregivers and 15 healthcare workers and County health officials between January to February 2025. Quantitative data were collected using structured questionnaires and analyzed in Stata version 17 through descriptive statistics, bivariate analysis at 20% significance threshold, and multivariable logistic regression at 5% level to determine key factors associated with malaria vaccine hesitancy. Qualitative data from 15 key informant interviews were transcribed verbatim and thematically analyzed using NVivo. Thematic analysis, guided by a predefined codebook, was used to identify recurring patterns and extract key themes, which were illustrated with direct quotations from participants Results: Overall, 42.9% of caregivers (n=181; 95% CI: 38.9%-47.3%) reported hesitancy. Significant predictors included caregiver age, marital status, family size, access to health facilities, and vaccine availability. Single caregivers, those from smaller households, and those facing health facility access challenges were more likely to be hesitant to malaria vaccine. Despite high levels of knowledge, misconceptions and misinformation about vaccine safety, often spread via social media persisted. Conversely, caregivers relying on healthcare workers and mainstream media showed greater acceptance of malaria vaccine. Conclusion and Recommendations: Malaria vaccine hesitancy remains significant at 42.9%, driven by demographic factors such as younger age, single status, and smaller household size. Structural barriers including limited vaccine availability and poor access to health facilities further contribute to reluctance. Although knowledge and awareness were high, misinformation, particularly from social media, persisted, while information from healthcare workers improved acceptance. Addressing these gaps through targeted community engagement, improved access, and trusted communication channels is essential to increase uptake of malaria vaccine.

Introduction The link between Human Papillomavirus (HPV) and cancer is well-established. In Singapore, bivalent HPV vaccines are subsidised for females, but not males. Economic analysis of HPV vaccination has generally assessed the costs to the health system, but this may not be as relevant to individual decision-making as potential lost income. We estimated the impact of bivalent HPV 16/18 vaccination on sick leave, unemployment, and premature mortality as a function of age and sex to understand the broader impact of HPV-related cancers. Methods We developed a population-level economic model to estimate lifetime income losses by diagnosis age, sex and cancer type. We applied sex- and cancer-specific Cox regressions to the Singapore Cancer Registry for annual predicted survival from 1992 to 2022. These were combined with census and employment data to estimate HPV-associated income losses in Singapore. Attributable fractions and vaccine effectiveness data for HPV 16/18 from the literature were used to estimate the effectiveness of bivalent HPV vaccination. Structural sensitivity analysis examined the role of 80% population coverage conferring herd immunity. Results The registry contained 17,294 individuals with an HPV-associated cancer diagnosis. Lost income was greatest for cervical cancer due to its high prevalence, however the losses per diagnosis were highest for oropharyngeal cancer. Bivalent HPV vaccination led to income benefits of $SGD1,397 [$895 to $1,838] in girls and -$62 [-$76 to -$48] in boys. A gender-neutral HPV vaccination of 80% of 15-year-old Singaporeans, conferring herd immunity, would have lifetime income protective benefits of $24.4m [$14.2m, $33.7m] per cohort, a five-fold return on investment. Conclusions In addition to avoiding healthcare costs and lost quality of life, parents should consider vaccination as a means of avoiding potential income losses. A national policy of gender-neutral HPV vaccination could deliver substantial income protection due to both individual vaccine protection and herd immunity.

Background: The U.S. 2024-2025 influenza season was characterized by sustained elevated activity from November 2024 to April 2025, with circulation of both influenza A(H1N1)pdm09 and A(H3N2), the latter of which included some antigenically drifted viruses. Methods: From October 1, 2024, to April 30, 2025, a multistate respiratory virus surveillance network enrolled adults hospitalized with acute respiratory illness in 26 U.S. medical centers. Influenza vaccine effectiveness (VE) against influenza-associated hospitalization and severe in-hospital outcomes was estimated using a test-negative study. The odds of influenza vaccination among influenza-positive case patients and influenza-negative control patients were compared using multivariable logistic regression; VE was calculated as (1-adjusted odds ratio for vaccination) x 100, expressed as a percent. Results: The 2024-2025 seasonal influenza vaccine was effective against influenza-associated hospitalization (VE: 40% [95% confidence interval (CI): 32%-47%]), consistent across age group and influenza A subtypes. Influenza vaccination also reduced the overall risk of all severe in-hospital outcomes evaluated, including standard oxygen therapy (VE: 41% [95% CI: 31%-50%]), non-invasive advanced respiratory support (VE: 38% [95% CI: 19%-52%]), invasive organ support (VE: 58% [95% CI: 44%-69%]), ICU admission (VE: 58% [95% CI: 47%-67%]), and death (VE: 52% [95% CI: 18%-71%]) with effectiveness varying by influenza A subtype and age. Conclusions: Influenza vaccination reduced the risk of influenza-related hospitalization and severe in-hospital outcomes in adults during the severe 2024-2025 influenza season compared to those not vaccinated.

Background: The 2024-25 influenza season was the most severe in the United States (US) since 2017-18, with co-circulation of both influenza A virus subtypes (H1N1 and H3N2). Influenza vaccine effectiveness (VE) has varied by season, setting, and patient characteristics. Methods: Using electronic healthcare encounter data from eight US states, we evaluated influenza vaccine effectiveness (VE) against influenza-associated hospitalizations and emergency department or urgent care (ED/UC) encounters from October 2024-April 2025 among children aged 6 months-17 years and adults aged 18+ years. Using a test-negative, case-control design, we compared the odds of influenza vaccination between acute respiratory illness (ARI) encounters with a positive (cases) versus negative (controls) test for influenza by molecular assay, adjusting for confounders. Results: Analyses included 108,618 encounters (5,764 hospitalizations and 102,854 ED/UC encounters) among children and 309,483 encounters (76,072 hospitalizations and 233,411 ED/UC encounters) among adults. Among children across care settings, 17.0% (6,097/35,765) of cases versus 29.4% (21,449/72,853) of controls were vaccinated. Among adults, 28.2% (21,832/77,477) of cases versus 44.2% (102,560/232,006) of controls were vaccinated. VE was 51% (95% confidence interval [95% CI]: 41-60%) against influenza-associated hospitalizations and 54% (95% CI: 52-55%) against influenza-associated ED/UC encounters among children. VE was 43% (95% CI: 41-46%) against influenza-associated hospitalizations and 49% (95% CI: 47-50%) against influenza-associated ED/UC encounters among adults. Conclusions: Influenza vaccination provided protection against influenza-associated hospitalizations and ED/UC encounters among children and adults in the US during the severe 2024-25 influenza season. These findings support influenza vaccination as an important tool to reduce influenza-associated disease.

Introduction: Modeling when influenza epidemics typically occur can help countries optimize surveillance, time clinical and public health interventions, and reduce the burden of influenza. Methods: We used influenza virus detections reported during 2011-2024 by 180 countries to the Global Influenza Surveillance and Response System, excluding COVID-19 pandemic impacted years (2020-2023). We analyzed data by calendar year (week 1-52) or shifted year (week 30-29) time windows, based on when most influenza detections occurred in each country. For countries with sufficient data, we computed generalized additive models (GAMs) of each country's weekly influenza-positive tests to smooth and impute time series distributions. From these GAMs, we calculated each country's normalized weekly influenza burden. Country-specific normalized time series were grouped using hierarchical k-means clustering reducing the Euclidean distance between time series within clusters. We calculated cluster-specific GAMs to estimate average seasonal timing. Countries without sufficient data were assigned to a cluster based on population-weighted latitudinal distance to a cluster's mean latitude. Results: We identified five clusters, or epidemic zones, from 111 countries with sufficient data. The influenza burden in epidemic zones A and B was consistent with a northern hemisphere pattern, with most influenza detections occurring during October-April (A) and September-March (B), while epidemic zones D and E were characterized by southern hemisphere-like seasonal timing, with most influenza burden occurring during May-November. Epidemic zone C had most influenza burden occurring during September-March; most countries assigned to this cluster were in the tropics. Conclusion: Epidemic zones may serve as a useful tool to strengthen and optimize influenza surveillance for global health decision-making (e.g., during vaccine strain composition discussions) and to guide country preparedness efforts for seasonal influenza epidemics, including the timing of enhanced surveillance, as well as the procurement and delivery of vaccines and antivirals.

Background Post-licensure vaccine effectiveness and impact studies provide evidence on how vaccines perform under routine programme conditions in the real world. In sub-Saharan Africa (SSA), vaccine introductions frequently coincide with concurrent public health and social measures that may influence disease risk and transmission. Failure to account for these concurrent interventions may affect the interpretation of vaccine effects. Methods We conducted a systematic review of post-licensure vaccine effectiveness and impact studies conducted in children under five years of age in SSA. Electronic databases were searched for peer-reviewed studies published between January 2000 and December 2019. Eligible studies used observational designs to estimate vaccine effectiveness or population-level impact. Two reviewers independently screened studies, extracted data, and assessed methodological quality using Joanna Briggs Institute tools. We examined study designs, vaccines evaluated, outcomes assessed, and whether public health and social measures (PHSMs) were measured or adjusted for. A narrative synthesis was undertaken. In addition, we conducted a meta-analysis for rotavirus and pneumococcal conjugate vaccines where we explored the heterogeneity in individual-level effectiveness estimates where designs and outcomes were comparable. Results Sixty-four studies met the inclusion criteria, covering eight vaccine-preventable diseases. Rotavirus vaccines were most frequently evaluated, followed by pneumococcal conjugate vaccines. Case-control and ecological designs were most common, while cohort and time-series analyses were less frequently used. None of the included studies collected, reported, or adjusted for PHSMs such as nutrition, WASH, or access to healthcare. The implications of this omission varied by pathogen. Rotavirus vaccine effectiveness estimates from comparable individual-level designs were consistent across settings, with no evidence of between-study heterogeneity. Pneumococcal vaccine effectiveness estimates showed substantial heterogeneity, which appeared to reflect differences in outcome definitions, host risk profiles, and study context. Estimates for other vaccines were generally protective in direction, although the magnitude and precision varied across studies. Conclusions Post-licensure vaccine effectiveness and impact studies in SSA rarely account for concurrent PHSMs. The consequences of this omission are not uniform across vaccines. For some pathogens, effectiveness estimates appear robust to unmeasured contextual change, while for others they are highly sensitive to outcome choice and setting. Future evaluations should prioritise systematic measurement of key PHSMs and consider study designs that better account for time-varying context. Strengthening routine data systems to capture these factors is essential for generating interpretable evidence to inform immunisation policy.

Blocking transmission of Borrelia burgdorferi (Bb), the causative agent of Lyme disease (LD), from reservoir hosts to humans via Ixodes scapularis ticks represents an alternative strategy to reduce LD incidence. Here, we evaluated Purified Borrelial Lipoproteins (PBL) with a combination of adjuvants, for their ability to limit Bb transmission using C3H/HeN mice and Peromyscus leucopus reservoir models. Immunization with PBL as oral gavage, either alone or nanoparticle-encapsulated, elicited increased antibody responses and reduced pathogen burden in fed larvae and select host tissues. A formulation combining PBL with a recombinant fusion protein adjuvant consisting of Cholera Toxin B subunit, Outer surface protein A, and two-tandem repeats of an M-cell-targeting peptide (rCOM) induced durable protective immunity for up to 10 months in C3H/HeN mice. This oral regimen significantly reduced Bb burden in host tissues, in fed larvae from vaccinated hosts, molted nymphs, and nymph-challenged naive mice. Immunization with PBL+rCOM elevated peripheral levels of Bb-specific IgG isotypes and increased antigen-specific T cell responses producing IFN-{gamma} and IL-4 at days 28 and 65 post-immunization. Significant protective responses were observed in P. leucopus, including strong antibody responses, reduced Bb burden in tissues and reduced Bb transmission to naive larvae, independent of sex but influenced by challenge dose. Sodium chloride content in oral formulation modulated vaccine induced protective responses. Notably, Bb burden in infected nymphs was reduced during the bloodmeal on vaccinated hosts with decreased pathogen transmission to both vertebrate hosts. These findings support PBL+rCOM as a promising oral, reservoir-targeted, transmission-blocking biologic for controlling Lyme disease. Lay AbstractNumerous vertebrate hosts serve as reservoirs of pathogens that are transmitted to humans via the bite of blood feeding vectors such as ticks. Lyme disease, caused by Borrelia burgdorferi (Bb), is the most common tick-borne disease in the US. Bb is transmitted to humans following the bite of infected Ixodes scapularis ticks. In nature, ticks acquire Bb and other pathogens from a variety of reservoir hosts, notably Peromyscus leucopus. Therefore, strategies that limit pathogen burden in reservoir hosts or block their transmission via ticks are options to prevent human infectious diseases, circumventing need for human vaccines and therapeutics. An oral, reservoir host-targeted, pathogen-derived, biologic prepared by extracting immunogenic lipoproteins (Purified Borrelial Lipoproteins) from Bb and combining them with a mucosal adjuvant derived by fusing Cholera-Toxin B subunit, Outer surface protein A of Bb and 2 repeats of an M-cell targeting peptide was tested in C3H/HeN mice and Peromyscus leucopus hosts. Single or two dose regimens via the oral route resulted in significant increases in peripheral Bb specific antibody responses, select T cell responses, blocking the transmission of Bb to naive Is larvae, reducing pathogen burden in vaccinated hosts, and interfering with the infectious cycle of the agent of Lyme disease.

Background: Pre-exposure prophylaxis (PrEP) is an effective HIV prevention tool, yet uptake and adherence remain low in Kenya despite integration into national HIV prevention plans since 2017. Intimate partner violence (IPV) is a prevalent HIV-related syndemic that presents barriers to PrEP engagement. While IPV's impact on women's PrEP use has been documented, less is known about IPV prevalence among men and its association with PrEP eligibility. This study aimed to determine IPV prevalence and explore correlates among PrEP-eligible men and women in coastal Kenya. Methods: This secondary analysis used data from the "Tambua Mapema Plus" trial conducted at six healthcare facilities in coastal Kenya among HIV-negative participants who were sexually active in the last 6 weeks and PrEP-eligible based on Kenya's Rapid Assessment Screening Tool. IPV was assessed through screening questions covering physical, verbal, and sexual violence experiences. Participants with ongoing IPV were excluded for safety. Among 1,500 intervention participants, 638 (402 women, 236 men) met PrEP eligibility criteria. Modified Poisson regression with robust standard errors was used to identify factors associated with IPV. Results: Overall, 24.1% reported lifetime IPV exposure, with 5.6% reporting past-month IPV. Women experienced higher rates of verbal (14.9% vs 11.0%), physical (15.2% vs 9.7%), and sexual IPV (11.2% vs 6.4%). Participants who had children (adjusted risk ratio [ARR]=2.09, 95%CI 1.32?3.32) or engaged in sex work (ARR=1.81, 95%CI 1.13?2.80) had increased IPV risk. In multivariable analysis, women with children had higher IPV risk (ARR=2.30, 95%CI 1.29?4.24), while men engaging in sex work had elevated risk (ARR=2.37, 95%CI 1.15?4.68). Discussion: IPV prevalence was substantial. Sex work emerged as a risk factor for both sexes, while having children increased risk among women. High IPV prevalence among PrEP-eligible individuals underscores the need for integrated IPV risk assessment in PrEP programs to improve HIV prevention effectiveness in Kenya.