Vaccine

West Nile virus (WNV) is the causative agent of fatal West Nile encephalitis. To date, no human vaccine against WNV has been approved. Adjuvants are important for developing effective and affordable vaccines that enhance the immunogenicity and decrease the required antigen doses. In this study, we assessed the efficacy of AddaS03, a synthetic adjuvant analogous to AS03, in a WNV subunit vaccine composed of soluble recombinant envelope protein (sEnv). Using a passive immunization mouse model, we defined the neutralizing antibody titer threshold required for protection against lethal WNV infections and applied this threshold as a surrogate marker to evaluate adjuvant efficacy. AddaS03-adjuvanted formulations elicited markedly higher neutralizing antibody titers compared to Alhydrogel adjuvant 2% (Alhydrogel), even at suboptimal antigen doses, and consistently exceeded the defined protective threshold titer. Moreover, in a sequential challenge mouse model, AddaS03-adjuvanted vaccines completely protected mice from symptomatic WNV infections, whereas Alhydrogel-adjuvanted vaccines failed to confer full protection. Collectively, these findings demonstrate that AddaS03 is a promising adjuvant for WNV subunit vaccine development and highlights the utility of a passive immunization model for defining protective antibody thresholds as a surrogate marker for vaccine evaluation.

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.

Typhoid fever remains a significant public health challenge in low- and middle-income countries. In 2018, The World Health Organization recommended a single dose typhoid conjugate vaccine (TCV) for routine immunization in endemic settings; however, evidence guiding booster doses remains limited. Homologous TCV booster doses have demonstrated immune boosting. This study assessed the immunogenicity and safety of a heterologous booster using a Vi capsular polysaccharide-CRM197 TCV (Vi-CRM) administered 5-6 years after primary vaccination with a Vi capsular polysaccharide tetanus toxoid TCV (Vi-TT) in children. Children previously enrolled in a Phase 2 trial were recruited. Participants who had received TCV at 9-11 or 15-23 months were given a Vi-CRM booster at 6-7 years of age (Booster-TCV group), and controls received their first TCV dose at the same age (1st-TCV group). Serum anti-Vi IgG concentrations were measured at baseline and 28 days post-vaccination. Solicited and unsolicited adverse events (AEs) and serious adverse events (SAEs) were recorded. Among 147 children enrolled, 87 received a second and 60 received a first TCV dose. Baseline anti-Vi IgG geometric mean titers (GMT) were higher in the Booster-TCV group (21.5 EU/mL; 95% CI: 17.2-26.8) than in the 1st-TCV group (5.5 EU/mL; 95% CI: 4.5-6.7). At day 28, GMTs rose markedly in both groups: 5140.0 EU/mL (95% CI: 4302.0-6141.3) in the Booster-TCV group and 2084.8 EU/mL (95% CI: 1724.4-2520.5) in the 1st-TCV group. Local reactions and systemic AEs were mild. No SAEs were observed. Vi-TT-induced immunity persisted for at least 5-6 years, and a heterologous booster triggered a strong immune response with universal seroconversion. These findings support heterologous prime-boost strategies to maintain protection in school-age children and inform optimization of TCV schedules in endemic regions.

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.

In a confirmatory study, we evaluated the immunogenicity and protective efficacy of a heterologous prime-boost vaccination strategy against respiratory syncytial virus (RSV) in non-human primates. Building on prior evidence of protective mucosal immunity induced by intramuscular DNA priming followed by an oropharyngeal adenoviral boost, we conducted a randomized, blinded, dual-centre study across two European primate research facilities. Rhesus macaques received a codon-optimized RSV-F DNA vaccine via electroporation, followed by two mucosal administrations of a recombinant adenovirus serotype 5 vector encoding the same antigen. Control groups included animals vaccinated with irrelevant influenza antigens and a comparator group mimicking natural immunity induced by primary RSV infection. Systemic and mucosal immune responses, including RSV-F-specific antibodies and tissue-resident memory T cells, were monitored longitudinally. Here, we detected robust immune responses, but with some variability between the two centres. However, following experimental RSV challenge performed 22 weeks after the final immunization, RSV-vaccinated animals demonstrated markedly reduced viral replication in both upper and lower respiratory tracts. However, unexpected RSV-specific immunity in the control group at one single study site prevented confirmation of the predefined primary endpoint. Overall, these results support the potential of mucosal adenoviral boosting following DNA priming to induce protective immunity against RSV, while highlighting challenges associated with multi-centre preclinical vaccine studies.

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.

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.

Background Childhood sensory and intellectual disabilities represent significant yet under-recognized barriers to learning and human capital development. This study analyzes prevalence and severity of these conditions among 149.3 million children aged 5-19 years across 25 countries in Latin America and the Caribbean (LAC) using Global Burden of Disease 2023 data. Methods We extracted GBD 2023 estimates for vision loss, hearing loss, and intellectual disability across 25 LAC countries, stratified by age, sex, and severity. Regional estimates were calculated using population-weighted averages. Severity distributions were compared with OECD countries to contextualize regional patterns. Results: These conditions are estimated to affected 9,282,921 children (6.22%; 95% UI: 5.89-6.54%). Hearing loss was predominant, affecting an estimated 5.42 million (3.63%, 3.41-3.86), with 87.6% mild-to-moderate. Intellectual disability estimated to affected 2.56 million (1.71%, 1.58-1.85), with 61.7% borderline-to-mild. Vision loss estimated to affected 1.30 million (0.87%, 0.79-0.96), with 89% that can be effectively addressed with spectacles. Prevalence increased with age across all conditions. Male predominance was consistent for intellectual disability (2.00% vs 1.42%). Annual economic cost totaled US$19.3-29.0 billion, while comprehensive interventions would require US$9.45-14.23 billion with benefit-cost ratios of 2:1 to 15:1. Conclusions The distribution of children across milder levels of difficulty underscores the opportunity for education and public health systems to provide timely and accessible support. With approximately 88% of sensory impairments addressable through established technologies, investments in inclusive services can yield strong social and economic returns.

While vaccination conflicts have become apparent, physicians' attitudes toward those with differing views remain unclear. Through an online survey of 492 physicians and 5,252 members of the general public in Japan in February 2026, we investigated attitudes toward four vaccines (influenza, measles, HPV, and COVID-19). Intergroup bias was assessed as ingroup minus outgroup attitudes using a feeling thermometer. Multilevel regression examined associations with agreement group and physician status. Intergroup bias was significantly positive in both agreement and disagreement groups across all vaccine types, and was higher in the agreement group. Physicians exhibited higher intergroup bias than the general public. These findings indicate that vaccination conflict is bidirectional: physicians, often viewed as targets of hostility from vaccine-hesitant individuals, themselves exhibit greater intergroup bias toward those with opposing views. Interventions to raise physicians' awareness of their own bias, alongside communication strategies for vaccine-hesitant individuals, are needed.

Background: Although the hemagglutination inhibition (HAI) titer remains the gold standard correlate of protection against influenza, it does not fully capture the broader antibody responses that contribute to immunity. Methods: We analyzed immune responses in paired pre-infection and convalescent sera from 306 RT-PCR-confirmed A/H3N2 infections from two household studies (2014-18) in Managua, Nicaragua. Antibody responses were measured by HAI and enzyme-linked immunosorbent assays (ELISAs) against full-length hemagglutinin (HA), the HA stalk, and neuraminidase (NA). Participants were classified as HAI responders ([&ge;]4-fold HAI rise), alternate responders (no HAI rise but [&ge;]4-fold boost in [&ge;]1 ELISA), or no-response individuals (no [&ge;]4-fold rise in any assay). We compared demographic, clinical, and pre-infection antibody characteristics across these groups. We also analyzed predictors of an NA response. Results: Overall, 77% of participants had HAI seroconversion or a 4-fold rise. Among the 23% HAI non-responders, 62% had alternate antibody responses. No-response individuals had the highest pre-infection HAI and full-length HA titers (p < 0.0001), the lowest viral loads, and the fewest fever or influenza like illness (ILI) symptoms (p < 0.01). An NA response was more common among symptomatic individuals (p = 0.0483) and those with low or high baseline NA titers. Conclusions: High baseline HAI titers can limit detectable 4-fold rises and are associated with milder illness. Evaluating additional immune responses may capture a more complete picture of the host response to infection, thereby improving surveillance and informing vaccine development. Keywords: Influenza A/H3N2; Hemagglutination inhibition (HAI); Neuraminidase antibodies; symptomatic vs asymptomatic infection; correlates of protection.

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.

Globally, respiratory tract infections (RTI) are the main cause of morbidity, and in Low-middle-income countries (LMICs) RTI including pneumonia are a leading cause of morbidity and mortality in children <5 years. Diarrheal illness increases RTI risk in young children through micronutrient depletion, and immune stress, yet data on post-diarrhea RTI burden in LMICs are limited. We determined the prevalence and risk factors of RTI within three months following medically-attended diarrhea (MAD) in children aged 6-35 months enrolled in seven EFGH country sites in Asia, Africa and South America. The EFGH study prospectively enrolled children aged 6-35 months with MAD in selected health facilities during a 24-month period from 2022 to 2024 and followed them for three months. RTI was defined as cough or difficulty breathing and the presence of one of the following symptoms at any scheduled or unscheduled visit during follow-up: stridor; fast-breathing; oxygen saturation <90%; or chest indrawing. The period prevalence and 95% confidence intervals of RTI were calculated, and correlates of RTI were assessed using modified-Poisson regression. From June 2022 to August 2024, 9,476 children aged 6-35 months presenting with MAD in the EFGH study sites were screened: 9,116 (96.2%) included in the current study. Nearly half were female (46.7%), and median age was 15 months. Overall, 48.5% received all age-appropriate vaccines, and 87.6% received the pneumococcal vaccine, with significant variation across countries. Nearly one-quarter of children were stunted, 17.2% wasted, and 21.9% underweight. RTI occurred in 3.8% of children during the three-month follow-up, mostly within the first month. Higher prevalence of RTI occurred among children aged 12-23 months (8.7%), those undernourished (16.1%), unvaccinated (4.0%) or living in poor sanitation settings (4.1%). While children who received all age-appropriate or pneumococcal vaccinations had a lower crude prevalence of RTI, these associations were not statistically significant after adjusting for age, sex and study site. RTI was infrequently observed in the three months following MAD presentation, with significant variability by site and with the highest prevalence in Malawi. RTI risk was highest in 12-23-month-olds and among children with undernutrition, and those living in poor sanitation conditions.

BackgroundZero-dose children, defined as those who have not received the first dose of a diphtheria-tetanus-pertussis-containing vaccine (DPT1), are a key indicator of inequitable access to immunization services. Nigeria remains one of the largest contributors to the global burden of zero-dose children. This study estimated the prevalence of zero-dose children aged 12-23 months and identified individual-and community-level determinants using the 2024 Nigeria Demographic Health Survey (NDHS). MethodsA secondary analysis of cross-sectional analysis was conducted using data from 4,711 children aged 12-23 months in the 2024 NDHS kids recode dataset. A multilevel mixed-effects logistic regression model was fitted to account for the hierarchical structure of the data. Four models were compared: null, individual-level, community-level, and combined models. Adjusted odds ratios (AORs) with 95% confidence interval (CI) were used to identify significant determinants at p<0.05. ResultsThe weighted prevalence of zero-dose children was 37.3% (95% CI: 35.1-39.6%). Significant factors included birth order, maternal age, maternal occupation, parental education, household wealth, antenatal attendance, postnatal care utilization, place of delivery, religion, distance to health facilities, and geographical region. Children whose mothers had higher educational attainment, attending antenatal care, deliver in the health facilities, and received postnatal care were significantly less likely to be zero-dose status. Conversely, children from poorer households, those facing distance barriers to health facilities, those belongings to Muslim and traditional religion group and those residing in certain geographical regions had higher odds of zero-dose children, with significant regional variations observed. Conclusionzero-dose vaccination remains highly prevalent in Nigeria and is strongly influenced by socioeconomic disadvantage, maternal healthcare utilization, religion, and regional inequities. Strengthening integrated maternal and child health services and improving access in underserved regions are essential to achieving equitable vaccination coverage.

IntroductionIncreasing global prevalence of overweight and obesity underscores the need for context-specific evidence to guide preventive policy implementation. Previous modelling showed that promoting healthy indigenous foods, implementing a 20% tax on sugar-sweetened beverages (SSBs), and introducing mandatory kilojoule menu labelling in formal-sector restaurants in Kenya were health-promoting, cost-saving, and cost-effective. Cost-effectiveness evidence is strengthened when considered alongside broader policy implementation considerations. We engaged stakeholders to assess additional implementation considerations relevant to decision-makers and to evaluate the stakeholder engagement process used in the modelling study. MethodsUsing the Assessing Cost-Effectiveness approach, we conducted a stakeholder-engaged study with national-level Kenya stakeholders recruited through purposive and snowball sampling. Through deliberative dialogue at a hybrid workshop, stakeholders assessed implementation considerations such as equity, feasibility and sustainability using a colour-coded scoring tool. We evaluated the engagement process using an anonymous survey covering seven stakeholder-engaged research domains. We analysed responses thematically. ResultsAcross the three interventions, most implementation considerations for feasibility, reach and impact, affordability, acceptability, and sustainability were assessed as medium or high. Industry acceptability of kilojoule labelling and SSB tax and affordability of kilojoule labelling to industry were rated low. Equity scores varied. Stakeholders proposed complementary measures that could raise low ratings to favorable scores. Clarity on stakeholder roles was identified as a key strength of the engagement process, while competing time commitments limited participation. ConclusionStakeholder insights contextualise prior cost-effectiveness evidence within policy-relevant implementation considerations and inform current fiscal and regulatory debates. Evaluation of the stakeholder engagement process underscores its contribution to strengthening public health research.

BackgroundThe Toto Bora trial tested whether a course of azithromycin reduced rates of re-hospitalization or death in the 6 months following hospitalization among Kenyan children. We hypothesized that azithromycin would reduce enteric bacteria and increase carriage of macrolide resistance in the subsequent 3 months. MethodsKenyan children (1-59 months) hospitalized and subsequently discharged for non-traumatic conditions provided fecal samples before and 3 months after randomization to a 5-day course of azithromycin or placebo. Quantitative PCR identified enteropathogens and AMR-conferring genes in fecal samples. Generalized estimating equations assessed the impact of the randomization arm on pathogen and resistance gene detection, accounting for baseline presence and site. ResultsAmong 1,393 baseline stools, 12.4% had at least one bacterial enteropathogen, 94.7% had at least one macrolide-resistance gene, and 92.6% had at least one beta-lactamase-resistance gene identified. At month 3, children randomized to azithromycin had a 6.1% higher likelihood of carrying a macrolide resistance gene compared to placebo (adjusted prevalence ratio [aPR], 1.06; 95% CI, 1.04-1.08; P<0.001). Specifically, azithromycin randomization was associated with a higher relative prevalence of erm(B) (aPR, 1.09 [95% CI, 1.04-1.15]; P=0.001), erm(C) (aPR, 1.23 [95% CI, 1.14-1.31]; P<0.001), msr(A) (aPR, 1.14 [95% CI, 1.04-1.25]; P=0.007), and msr(D) (aPR, 1.07 [95% CI, 1.03-1.11]; P=0.001). There was no difference in overall bacterial pathogen prevalence (18.9% vs 17.3%) between randomization arms, but a slightly lower proportion of children had Shigella after randomization in the azithromycin arm (3% vs. 5%, aPR, 0.79 [95% CI, 0.62, 1.01]; P=0.063). InterpretationAzithromycin at hospital discharge was associated with higher carriage of macrolide-resistance-conferring genes in the post-discharge period compared with placebo, without significant declines in enteric pathogen carriage other than modest changes to Shigella. The potential benefits and risks of empiric azithromycin need to be considered, as children are increasingly exposed to this broad-spectrum antibiotic.

BackgroundDespite advances in therapy, optimal management of juvenile idiopathic arthritis (JIA) remains challenging. The ability to predict disease progression in JIA can improve personalized treatment decisions, but few reliable clinical predictors have been identified. We developed machine learning approaches to predict disease trajectories in children with JIA. MethodsUsing data from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry (years 2015-2024), we developed machine learning models to predict attainment of inactive disease in children with non-systemic JIA. We applied Dynamic Bayesian Networks (DBN) to model temporal dependencies and causal relationships, and Convolutional Neural Networks (CNN) to capture complex non-linear patterns. Model input included demographic factors, longitudinal clinical factors, and medication use in the preceding 12 months. FindingsA total of 8,093 participants were included. When tested on an independent test cohort, both DBN (AUC:0.76; precision:0.73; recall:0.83; F1-score:0.78; accuracy:0.71) and CNN (AUC:0.76; precision:0.71; recall:0.63; F1-score:0.67; accuracy:0.70) models achieved comparable performance in predicting inactive disease. Disease activity levels in the preceding 12 months, presence of enthesitis and uveitis were the strongest predictors. Causal relationships captured in the DBN model revealed suboptimal care patterns, likely shaped by insurance constraints and a predominantly reactive approach to JIA management. InterpretationOur study demonstrates that machine learning approaches can predict disease trajectories in JIA with good discriminative performance. Unlike prior studies that predict outcomes at single timepoints, our models are the first to predict inactive disease longitudinally. However, suboptimal care patterns in retrospective data limit models capacity to learn treatment-outcome relationships, underscoring critical opportunities to improve JIA care and the need for prospective comparative studies to better inform prediction models. FundingPatient-Centered Outcomes Research Institute (PCORI) Award (ME-2022C2-25573-IC). RESEARCH IN CONTEXT Evidence before this studyNumerous studies have sought to identify clinical predictors of JIA progression and outcomes. However, few reliable predictors have emerged and existing prediction models demonstrate limited performance. As a result, our ability to personalize treatment decisions based on individual risk of severe disease course remains limited. Added value of this studyWe developed novel machine learning models that predict individualized disease trajectories in children with polyarticular and oligoarticular JIA using data from their preceding 12-month clinical course. These models demonstrated strong discriminative performance and outperformed previously published machine learning approaches in JIA. Unlike prior studies limited to single time-point predictions, our models are the first to predict inactive disease longitudinally, enabling a patient-specific projection of disease progression over time. Importantly, our findings also bright to light patterns of suboptimal care, likely driven by insurance constraints and a reactive treatment paradigm, underscoring critical opportunities to improve JIA management. Implications of all the available evidenceOur models have the potential to support clinical decision-making by enabling early identification of children with JIA at risk for unfavorable disease trajectories. In addition, the suboptimal care patterns and systems-level barriers identified through our analyses highlight priority areas for quality improvement initiatives and policy interventions to reduce gaps in JIA care delivery.

OBJECTIVE: To evaluate the return on investment (ROI) of a community based Diabetes Self Management Program (DSMP) enhanced with health related social needs (HRSN) screening and referrals, implemented by the New York City (NYC) Department of Health and Mental Hygiene with three community based organizations in highly impacted, under resourced neighborhoods. RESEARCH DESIGN AND METHODS: A retrospective cost benefit analysis from a public sector payer perspective was conducted among 171 adults with type 2 diabetes who completed a six week, peer led DSMP delivered by community health workers (CHWs) in English, Spanish, and Korean during 2018 2019. A time driven, activity based costing model captured direct implementation costs, CHW workforce turnover, and administrative overhead. Monetized benefits included avoided diabetes related complications, reductions in self reported emergency department (ED) visits and hospitalizations, and quality adjusted life year (QALY) gains from improved medication adherence. Univariate sensitivity analyses tested robustness under conservative assumptions. RESULTS: Total program costs were $179,224; monetized benefits totaled $1,824,213, yielding a net benefit of $1,644,989 and an ROI of 918%, approximately $10 returned per $1 invested. Excluding QALY gains, ROI remained 551%. Self reported ED visits declined from 149 to 82 and hospitalizations from 93 to 24 in the six months following intervention. Over 80% of participants reported housing instability; 72% were Medicaid covered and 16% uninsured. Sensitivity analyses confirmed a positive ROI under all conservative scenarios. CONCLUSIONS: A CHW led, community based DSMP integrated with HRSN screening and referrals delivered substantial economic and public health value among adults facing housing instability and structural barriers to care. Findings support inclusion of DSMP as a covered benefit in Medicaid managed care, value based payment arrangements, and housing access initiatives to advance equitable diabetes outcomes.

In recent years, immunotherapy of patients with higher-risk non-muscle invasive bladder cancer (NMIBC) in North America has relied on the use of the TICE strain of BCG. However, limitations in the supply chain have warranted investigation of the therapeutic benefit of other strains of BCG, such as BCG-Russia. Trained immunity, a form of innate immune memory, is now widely believed to be an important component of the therapeutic benefit of BCG. Therefore, in the present study we compared the effects of BCG-TICE and BCG-Russia on the acquisition of trained immunity and related secondary immune responses. C57BL/6 mice received a single intravenous injection of BCG-Russia or BCG-TICE. Four weeks later, bone marrow was collected for flow cytometric analysis of hematopoietic stem and progenitor cell (HSPC) populations, generation of bone marrow-derived macrophages, functional assessment of trained immunity, and transcriptomic profiling. Compared with BCG-Russia, BCG-TICE elicited stronger levels of trained immunity, characterized by higher production of several proinflammatory cytokines upon secondary activation. BCG promoted the expansion of HSPCs independent of strain. BCG-TICE was linked to upregulation of key inflammation-related genes and enrichment of functionally relevant pathways. The results of this study reveal strain-dependent differences in the ability of BCG to induce innate immune memory and inflammatory pathways that could ultimately determine efficacy of immunotherapy of patients with NMIBC.

Background Individuals experiencing or at risk of homelessness face substantial barriers to preventive eye care that are poorly addressed by standard service models. Interdisciplinary optometry-social work collaboration offers a rights-based approach to improving engagement and continuity of care. Methods A convergent mixed-methods study was conducted between February and August 2024 at a multidisciplinary community centre. Clients experiencing or at risk of homelessness received integrated optometry and social work assessment and were prioritised as high, medium, or low based on combined clinical and social risk. Social work follow-up was guided by the Triple Mandate and W-Questions framework. Quantitative data were summarised using mean (SD), median [IQR], or n (%). Qualitative case notes were analysed using content analysis with inductive coding and secondary review for consistency. Results A total of 165 clients had priority categories coded (high: 68; medium: 47; low: 154). Demographic data were available for 132 clients (60% male; mean age 49.5 years [SD 16]); 27% had not completed high school, 89% reported weekly income below AUD 1000, and 28% had vision impairment. Two hundred forty-five case-note entries were consolidated into 146 unique records. SMS (46%) and phone calls (38%) were the most documented contact methods, although only 21% of calls were answered; missed calls (13%) and disconnected numbers (7%) were common. Multi-modal contact was more frequently documented for higher-priority clients. Appointment assistance was the most recorded facilitator (71%), while rights-based supports, including interpreter and transport assistance, were infrequently documented (<=5%). Qualitative analysis identified unstable communication, reliance on informal supports, and service fragmentation as key influences on recall outcomes. Conclusion This study supports an interdisciplinary, rights-based optometry-social work model to address barriers to preventive eye care among people experiencing or at risk of homelessness. Embedding structured handovers and tiered recall processes within community-based services may strengthen continuity and accountability for high-priority clients. Future implementation should evaluate outcomes related to equity of reach, service integration, and sustained engagement in care.

BackgroundAccess to safe, equitable, and affordable surgical and anesthesia care is critical to reducing the burden of surgical diseases in Africa. To understand the state of access in South Sudan, we conducted a baseline assessment of surgical services in Central Equatoria State (CES) in May 2024. ObjectivesThis study aimed to survey public healthcare facilities in CES capable of providing essential surgical services. We used the capacity to perform cesarean section, laparotomy, and open fracture management--Bellwether procedures--as a proxy for assessing workforce, infrastructure, financing, information management, and service delivery. MethodsWe used a validated and contextualized Surgical Assessment Tool developed by the Harvard Program on Global Surgery and Social Change and the World Health Organization. Data were collected at the facility level and summarized descriptively using percentages, means (standard deviations), medians (minimum, maximum), and visualized in graphs, charts, and tables. ResultsAll three public health facilities assessed could perform Bellwether procedures for their catchment populations. However, workforce availability, financing, and surgical infrastructure were major constraints. The surgical workforce density was 2.27 surgical, anesthesia, and obstetric specialists per 100,000 population. Specialized procedures--such as repair of cleft lip and palate, clubfoot, and hydrocephalus shunt--were unavailable at all sites. None had magnetic resonance imaging (MRI) machines. The total average annual facility budget was $918,850, ranging from $3,960 to $800,000 at the teaching hospital--insufficient for proper operations. ConclusionWhile Bellwether procedures are routinely performed, access to quality and affordable care is compromised by deficits in workforce, financing, and infrastructure. We recommend that the Ministry of Health scale this survey nationally and develop a surgical policy and strategic plan focused on improving infrastructure, workforce, and financing for surgical and anesthesia care in South Sudan.