The Lancet Regional Health - Americas

BackgroundAlthough the impact of COVID-19 vaccination is widely documented in the general population, the evidence on its effectiveness in children under 5 years of age is still limited. In this context, the continuation of vaccination programs in this age group has been debated globally. Consequently, we estimated the effectiveness of the 3-dose series of BNT162b2 (Pfizer-BioNTech) in children aged 6 months to 4 years and the complete 2-dose series of CoronaVac (Sinovac) in children aged 3 to 4 in reducing the risk of hospitalizations due to COVID-19-attributed severe acute respiratory infection (SARI) in Brazil. MethodsWe conducted a retrospective cohort study in 24 Brazilian municipalities, using surveillance data. We evaluated vaccine effectiveness in reducing the incidence rate of COVID-19-attributed SARI hospitalizations from July 2023 to December 2024. Covariate adjustments, defined a priori based on a conceptual model represented by a directed acyclic graph (DAG), were implemented using random-effects Poisson regression models. We also analyzed alternative vaccination schedules and obtained age-specific estimates of effectiveness. ResultsThe cohort comprised 37.6 million person-months of follow-up and 1,384 COVID-19-attributed SARI hospitalizations, including 27 associated deaths. The 3-dose series of BNT162b2 vaccine had an effectiveness of 97% (IRR 0.03, 95%CI 0.01-0.10) in the group aged 6 months to 4 years, with no significant differences among age-specific estimates. No deaths occurred among children who completed the 3-dose series, whereas four deaths were observed among those with fewer doses. The effectiveness of CoronaVac was small and not statistically significant (IRR 0.96, 95%CI 0.57-1.62). However, no deaths were recorded among children who received any number of CoronaVac doses, and no COVID-19-attributed SARI hospitalizations were observed among those who received a third dose of this vaccine. ConclusionsThe 3-dose series of the mRNA vaccine (BNT162b2) had high and consistent effectiveness in protecting against severe COVID-19 in children aged 6 months to 4 years. These findings support the maintenance of routine COVID-19 vaccination in this age group.

BackgroundResearch infra-structure is essential for conducting phase III cancer clinical trials as its lack precludes trial availability and its maturity may influence the portfolio of available options. Several studies have highlighted global disparities, but none has ever mapped the worldwide network of research facilities conducting such trials. MethodsWe extracted all research sites within recruiting phase III cancer interventional trials from the ClinicalTrials.gov database on July 23, 2024. Address components were combined and queried through the Google Maps API for standardized identification. Matched pairs were subsequently screened for inconsistencies, and Google Maps entries within 1,000 meters were grouped if they represent the same facility. We compared research facilities number, density (per 1M inhabitants), size, and portfolio of available trials across World Development Index regions, and modelled the number of available trials and research facilities per country with log-log linear models (elasticity coefficient [{beta}] estimand). FindingsOf 77,625 listed sites from 1,287 trials, 65,736 (84.7%) were mapped to 6,634 unique research facilities across 84 countries. We found a strong correlation between the number of research facilities and trials by country (R2=0.86, p-value<0.001, {beta}=0.95, 95%CI 0.87-1.04). The United States and China had the largest number of facilities (2,626, 39.6%) and available trials (624, 48.5%) respectively. All the 100 largest research facilities in size were from high-income countries or China, and 16 of the top 20 countries by density were located in Europe and Central Asia. Latin America and Caribbean, South Asia Region, and Sub-Saharan Africa had the highest proportion of facilities running only multiregional (>93%, p-value<0.001), industry-sponsored (>90%, p-value<0.001), and systemic therapy trials (>80%, p-value<0.001). InterpretationPhase III cancer trials are directly limited and responsive to physical institutional growth. Outside high-income countries, research capacity remains substantially constrained, largely focused on systemic therapies and frequently reliant on industry-sponsored, multiregional trials. FundingNone RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSWe searched the Pubmed/EMBASE database for studies investigating cancer clinical trials and research facilities distribution worldwide using the search terms "trials OR clinical trials", "cancer", "distribution OR barriers OR access OR inequalit*" between inception to November 1st, 2025. Several studies have consistently shown a higher concentration and availability of cancer clinical trials in high-income countries (HIC) compared to lower-income regions. In addition, cancer clinical trials in lower middle-income countries (LMIC) are predominantly phase III, industry-sponsored, and led by HIC. However, most of this evidence is derived from country-level aggregate data, which collapse heterogeneous research infrastructures within countries into single summary measures and therefore lack the resolution needed to describe, and ultimately explain the underlying drivers of these disparities. Only a small number of studies have examined cancer trial distribution at finer geographic scales, and these have generally been limited to city or county-level analyses or to single-country settings. Therefore, there remains no comprehensive mapping of the research infrastructure responsible for conducting cancer clinical trials, even though this infrastructure is a key determinant of national trial availability and study profiles. Added value of this studyThis is the first study to map and profile research facilities conducting phase III cancer clinical trials worldwide. We show that the availability of phase III cancer clinical trials is linearly correlated with the absolute number of research facilities on a log-log scale, such that a 1% increase in research facilities is associated with a 0.95% (95%CI, 0.87-1.04) increase in phase III trial availability within countries. The United States had the largest share of research facilities (N=2,626, 39%) while China had the highest number of available phase III clinical trials (N=624), driven by a high number of single-center studies (N=398). Of the largest 100 research facilities in size (median [IQR] number of phase III cancer trials 62 [57-73.25]), all were from HIC or China. Of the top 20 countries by density (per million people), 80% were located in Europe and Central Asia (ECA). In Latin America and Caribbean (LAC), South Asia Region (SAR) and Sub-Saharan Africa (SSA), research facilities are found in fewer numbers and smaller sizes, and are predominantly running only multiregional (>93%), industry-sponsored (>90%), and systemic therapy trials (>80%). Implications of all the available evidenceGlobal disparities in cancer clinical trials are perpetuated by constrained research infrastructure in less developed regions, reflected not only in the limited number of research facilities but also in their profiles, which often have little experience beyond industry-sponsored trials, as we have shown. While investments in research facilities are crucial and are associated with increased trial availability, particularly during the early stages of infrastructure development, they are not sufficient on their own. Complementary strategies are needed, including financial incentives to support locally designed trials (i.e., investigator-initiated grants) and sustained investment in human resources to design and conduct them. Aligning infrastructure expansion with workforce development is essential to improve both the quantity and the profile of available cancer clinical trials, enhance local leadership, and ensure that research is relevant and generalisable to diverse populations.

BackgroundApproximately 300 million people worldwide live with a rare disease, and the majority of rare diseases manifest in childhood. For families, the period before diagnosis is often protracted and distressing, marked by repeated consultations, inconclusive investigations, conflicting medical opinions, and the absence of a recognisable name for their childs condition. While the clinical and epidemiological dimensions of the diagnostic odyssey have been documented, the narrative and experiential dimensions of how parents live through and make sense of prolonged diagnostic uncertainty remain underexplored, particularly in low- and middle-income country contexts. AimTo explore the narrative experiences of parents navigating diagnostic uncertainty for children with rare diseases in Brazil. MethodsA narrative inquiry informed by the three-dimensional narrative space framework of Clandinin and Connelly was conducted. Sixteen parents (twelve mothers and four fathers) of children who had experienced a diagnostic delay of at least two years were recruited from two rare disease referral centres in Sao Paulo and Belo Horizonte. Data were collected through two narrative interviews per participant, supplemented by participant-produced timelines and family photographs. Analysis followed a narrative analytical approach attending to temporality, sociality, and place. FindingsThree narrative threads were woven across the parents stories: (a) "Living in the space before the name," capturing the disorienting experience of caring for a child whose suffering could not be categorised, explained, or predicted; (b) "Fighting to be believed," describing the relentless advocacy required to sustain medical attention in a system that struggled to accommodate conditions falling outside familiar diagnostic categories; and (c) "Rewriting the story," illuminating how the eventual arrival (or non-arrival) of a diagnosis reshaped parents understanding of their child, their family, and themselves. ConclusionDiagnostic uncertainty for parents of children with rare diseases is not a passive waiting period but an active, effortful, and identity-transforming experience. The findings highlight the need for healthcare systems to provide structured psychosocial support during the pre-diagnostic period and for clinicians to develop communication practices that acknowledge, rather than dismiss, the legitimacy of undiagnosed suffering.

BackgroundThe province of Quebec has progressively implemented paired tumour-germline sequencing in paediatric oncology through two coordinated precision research programs, preceding a province-wide mainstream clinical genomics initiative. We report the prevalence, spectrum, and clinical relevance of germline findings (GFs) in children with primary extracranial cancers, integrating molecular, phenotypic, and pathological data. MethodsPatients enrolled between 2014 and 2022 underwent germline whole-exome sequencing (WES) using a virtual 352-cancer gene panel. Sequencing, bioinformatics and variant interpretation followed best practices standards based on GATK, ACMG/AMP and ClinGen recommendations. Somatic WES and transcriptomic data were integrated when available. GFs were categorised as diagnostic findings (DFs; established or suspicious association with the cancer phenotype) or as other findings further subcategorised according to actionability and age of disease onset. FindingsAmong 484 children, 130 (26.9%) carried 149 GFs, including 49 (10.1%) with a DF (42 with well-established associations with cancer phenotypes). DFs involved 21 genes related to childhood cancer predisposition, trisomy 21 and one clinical Beckwith-Wiedemann syndrome. Six DFs were initially missed by standard exome pipelines, and mosaic constitutional cancer predisposition syndrome (CPS) was confirmed in 4/49 children, underscoring the value of integrative analyses. A CPS was known at the time of primary cancer in 10/49 children. Among those diagnosed with a CPS after cancer onset, suggestive phenotypic features were present in 36/39. Other non-diagnostic findings were identified in 92 children; 21 (4.3% of the cohort) with actionable implications in childhood (n=7) or adulthood (n=14). Somatic sequencing was informative for refining causality, as somatic second hit alterations were identified in 29/33 (87.9%) DFs involving monoallelic tumour suppressor genes, whereas no such alterations were observed in non-DFs counterparts (0/57; p<0.0001). Interpretation: This provincial research experience highlights the analytical and practical challenges of germline evaluation in paediatric oncology and supports a shift toward integrative interpretation frameworks combining complementary germline, somatic, pathology, and phenotypic data. Flexibility in investigative strategies and nuanced categorisation of findings are warranted, guided by a child-centred interpretative framework. This approach underpins Quebecs paediatric oncology genomics mainstreaming initiative.

PurposeTo describe the rationale, methods, and baseline sample descriptives of the Adolescent and Young Adult Tracking Engagement and Management Skills (AYA TEAMS) cohort. The AYA TEAMS study is a longitudinal observational cohort study that aims to identify determinants and patterns of self-management and engagement in cancer-related long-term follow-up (LTFU) care and validate a novel transition readiness assessment among adolescent and young adult (AYA) survivors of childhood cancer. ParticipantsAYA survivors of childhood cancer (ages 16-25) and their caregivers were enrolled from 3 large pediatric oncology centers across the United States from 2020-2022 and followed for 2 years (minimum) to 3 years and 3 months (if transferred to adult care). AYA inclusion criteria were: past childhood cancer diagnosis, at least 2 years off-treatment, 5 years since diagnosis, engaged with the participating pediatric health care system within the last 18 months, cognitively able to complete study procedures, and English speaking. AYA completed a comprehensive battery of measures including assessments of self-management and transition readiness at baseline and annually for 2 years. For AYA transferred to adult care, separate measures were administered at the time of transfer (following last pediatric visit) and 15 months post transfer. Caregivers (English or Spanish-speaking) completed a single survey at baseline to capture family functioning, psychosocial risk, and transition readiness. Cancer diagnosis, treatment modalities, treatment-related late effects, and engagement in LTFU care were captured via electronic medical record review. In total, 709 AYA were enrolled and 587 were included in the final cohort [Mage=19.7 years, 52.5% female, 38.2% from racial and/or ethnic minoritized groups, (REMG)]. The cohort was on average 7.3 years old at the time of diagnosis and 10.5 years off treatment. Half (52.5%) were survivors of leukemia/lymphoma, 38.0% solid tumors, and 9.5% central nervous system tumors. Three hundred and ninety-nine caregivers participated (90% mothers). Findings to DateEnrolled AYA excluded from the baseline cohort were more likely to be male, from REMG, and/or to enroll without a caregiver. Baseline cohort differences between sites emerged for age, race and ethnicity, socioeconomic status, and treatment modalities and intensity. Future PlansData collection was completed in April 2025. Findings from this cohort will elucidate important predictors of self-management and engagement in recommended annual LTFU and inform the design of interventions to reduce disengagement in LTFU. Strengths and LimitationsO_LIThis study is the first known prospective cohort of AYA-only long-term survivors of childhood cancer in the United States recruited from pediatric cancer centers. C_LIO_LIThis study achieved high enrollment and retention rates across a medically and demographically diverse sample. C_LIO_LIInformed by multiple theoretical self-management models, this study will be able to examine predictors and transactional relationships of AYA survivor self-management, including engagement in pediatric and adult cancer-related long-term follow-up care. C_LIO_LIReliance on English-speaking AYA and those currently engaged with the health care system are limitations. C_LI

BackgroundTimely cancer diagnosis in children and adolescents is critical to improving outcomes, yet substantial variation in diagnostic intervals persists across cancer types and care settings. We aimed to quantify time to diagnosis and assess variations by patient, demographic, and system-level factors. MethodsWe conducted a retrospective population-based study of children and adolescents aged 0-19 years diagnosed with one of 12 common cancers between 2010 and 2022 in Quebec, Canada. The diagnostic interval was defined as the time from first cancer-related healthcare encounter to diagnosis. We calculated medians and interquartile ranges (IQR) overall and by cancer type and used multivariable quantile regression to identify factors associated with time to diagnosis at the 25th, 50th, and 75th percentiles. ResultsAmong 2,927 individuals with cancer, diagnostic intervals varied by cancer type and age. Median intervals were longest for carcinomas (100 days; IQR 33-192) and shortest for leukemias (8 days; IQR 3-44). Compared with children living in Montreal, living in regional areas and other large urban centres was associated with longer 50th and 75th percentiles of time to diagnosis for hepatic and central nervous system (CNS) tumours. Diagnostic intervals were shorter in the post-pandemic period (2020-2022) across several cancer sites, with CNS tumours showing reductions across all quantiles. InterpretationDiagnostic timeliness differed by cancer type, age, and rurality, but not by sex, material, or social deprivation. The shorter diagnostic intervals observed in the post-pandemic period suggest that pandemic-related changes in care pathways may have expedited diagnosis for some cancers.

The spread of extended-spectrum {beta}-lactamase (ESBL)-producing and fluoroquinolone-resistant Salmonella pose a global public health challenge in addition to the high burden of infections associated with this foodborne pathogen. In this study we aimed to characterize a multidrug-resistant strain of Salmonella serovar Amager isolated from a Chilean river in October 2023. Antimicrobial susceptibility testing revealed a resistance phenotype against multiple antibiotic families, including fluoroquinolones and {beta}-lactams, showing ESBL production. Hybrid genome sequencing allowed the identification of a 311,303 bp plasmid carrying the aadA1, aph(4)-Ia, aac(3)-IVa, floR, sul1, tet(A), and blaCTX-M-65 genes, sharing 99.98% sequence identity with the Salmonella Infantis pESI-like megaplasmid. In addition, the qnrB19 gene was found in a {approx}2.7 kbp plasmid of widespread distribution. Population structure and temporal phylogenetic analysis at the global scale revealed the emergence of a Salmonella Amager lineage from the HC20_35565 cluster, carrying the Salmonella Infantis blaCTX-M-65-positive pESI-like megaplasmid and causing human infections in the United States and the United Kingdom. Our work describes the emergence of a Salmonella lineage with resistance against first-line antibiotics used for treating severe infections, underscoring the relevance of environmental surveillance as a means for detecting emergent pathogens and anticipating human infections.

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.

ImportancePersistent racial and ethnic disparities in breast and prostate cancer mortality are well documented. Most prior studies emphasize between-group differences and rely on population averages or single composite measures of social disadvantage, which can obscure high-need communities within groups. How socio-behavioral determinants of health vary within groups across local gradients of cancer mortality remains incompletely characterized. A framework that combines race- and cancer-specific mortality with local, domain-level socio-behavioral profiles may help identify where burden is greatest and which specific barriers warrant prioritization. ObjectiveTo determine how socio-behavioral risk relates to breast and prostate cancer mortality within racial and ethnic groups and to characterize domain-specific behavioral profiles across low-, moderate- and high-mortality counties to inform targeted, equity-oriented cancer control strategies. DesignCross-sectional study of U.S. counties. Setting United States, county-level analysis. Participants3,141 U.S. counties, stratified within Non-Hispanic White, Non-Hispanic Black, and Hispanic populations. ExposuresCounty-level socio-behavioral determinants of health measured using a composite index comprising seven domains: community solidarity; education, health literacy, and digital connectivity; quality of care; housing and environmental risk; economic livelihoods; lifestyle behaviors; and touchpoints with care. Main outcomes and measuresRace/ethnicity-specific, age-adjusted breast and prostate cancer mortality rates (2018-2022) and county-level socio-behavioral risk scores. Counties were grouped into mortality tertiles within each race/ethnicity-by-cancer-stratum. ResultsAcross groups, higher socio-behavioral risk was associated with higher breast and prostate cancer mortality. For breast cancer, socio-behavioral risk increased monotonically across mortality tertiles for all groups, with the largest within-group increases among Hispanic and Non-Hispanic Black women. For prostate cancer, risk generally increased across mortality tertiles for all groups. Although Hispanic populations had lower population-average mortality, high-mortality Hispanic counties exhibited pronounced risk in lifestyle behaviors, economic livelihoods, and touchpoints with care. Domain patterns associated with high mortality varied by race, ethnicity, and cancer type, with touchpoints with care and economic livelihoods consistently prominent. Conclusions and relevanceWithin-group heterogeneity in socio-behavioral risk is substantial across U.S. counties. Linking population-specific, domain-level socio-behavioral profiles to cancer mortality may support more precise and equity-oriented cancer control strategies than reliance on group averages or composite indices. Key pointsO_ST_ABSQuestionC_ST_ABSWithin racial and ethnic groups, how do socio-behavioral determinants of health vary across US counties with low, moderate, and high breast and prostate cancer mortality? FindingsIn this cross-sectional study, higher county-level socio-behavioral risk was associated with higher breast and prostate cancer mortality across racial and ethnic groups. Race/ethnicity-specific, domain-level profiles revealed within-group heterogeneity, including persistently elevated risk among Non-Hispanic Black populations and pronounced domain-specific gaps in high-mortality Hispanic counties. MeaningLinking population-specific socio-behavioral profiles to local cancer mortality can guide more precise and equity-oriented prioritization of intervention domains and geographies than reliance on group averages or composite indices.

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

A recent randomized clinical trial in non-small cell lung cancer1 confirms what numerous observational studies have reported - time-of-day (ToD) may dramatically influence treatment outcomes in cancer patients2-9. In this recent trial median overall survival (OS) decreased from 28 months in the early ToD arm to 16.8 months in the late ToD arm. We raise the concern that clinical trial outcomes may be influenced by seemingly minor biases in treatment time across arms. We also suggest that by measuring or randomizing treatment-time in clinical trials, we may identify beneficial ToD-dependent treatments that would otherwise be overlooked.

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBackgroundC_ST_ABSEnsuring appropriate access to essential antibiotics is a critical global public health goal. The UN General Assembly agreed that 70% of global antibiotic use should be WHO Access group. A standard method to estimate optimal antibiotic use based on burden of disease, resistance and local context is needed to inform national policies. MethodsUsing data from multiple global datasets, we clustered 186 countries, territories and areas (CTAs) into peer groups based on sociodemographic factors, infection and resistance incidence using a latent class model. Within each cluster, benchmark countries with low antibiotic use and infection mortality were identified. We estimated optimal Total DID given infection burden, Reserve DID based on relevant resistance burdens, Watch DID based on clinical infections requiring Watch antibiotics from the WHO AWaRe Book and Access DID as the residual volume. FindingsGlobally 43.0 billion DDDs (95%CI:35.4billion-57.7billion) of antibiotics in 2019 were needed in 186 CTAs, of which 76% would optimally be Access (95%CI:70%-82%). CTAs in lower-income clusters required more Watch and Reserve antibiotics than higher income CTAs. Among CTAs with actual use data available, 72% (48/67) of CTAs used more Total and 99% (66/67) used more Watch antibiotics than estimated optimal levels. ImplicationsWe present the first estimates of optimal AWaRe antibiotic levels for 186 CTAs. After accounting for country-specific needs, the UNGA 70% Access target is globally appropriate. AWaRe benchmarking enables CTAs to estimate under and overuse of AWaRe antibiotics to inform national policies. FundingThe ADILA Project funded by the Wellcome Trust [222051/Z/20/Z]. RO_SCPLOWESEARCHC_SCPLOWO_SCPCAP C_SCPCAPO_SCPLOWINC_SCPLOWO_SCPCAP C_SCPCAPO_SCPLOWCONTEXTC_SCPLOWO_ST_ABSEvidence before this studyC_ST_ABSMember states agreed at the 2024 United Nations General Assembly (UNGA) AMR meeting that the WHO AWaRe (Access, Watch, Reserve) system should underpin global antibiotic surveillance and that 70% of global use should be from the AWaRe Access group, while accounting for national contexts but did not agree any method for derived country-level targets. The WHO GLASS antimicrobial use (GLASS-AMU) surveillance system and other studies have reported observed antibiotic use. GLASS reports actual national medicine-level antibiotic use from 2015-2022 for 60 CTAs. The GRAM study (Browne, et al., 2021) modelled estimated total antibiotic use from 2000-2018 for 204 CTAs but were only able to estimate AWaRe antibiotic use for 76 CTAs where data from the commercial IQVIA MIDAS(R) database were available. Recent estimates from Klein et al. (2024) reported changes in antibiotic use from 2016 - 2023 for 67 CTAs in IQVIA MIDAS(R). Despite these studies quantifying estimates of current national medicine-level antibiotic use, there are very few estimates of what levels of antibiotic use are "optimal" both overall and by AWaRe group. We searched PubMed for studies from January 2015 through October 2025 on national-level antibiotic targets and AWaRe antibiotic policy using Boolean search terms. We identified few studies that estimated optimal levels of antibiotic use, but none for all AWaRe groups. As part of the Lancet AMR series, Mendelson et al. (2024) estimated expected total antibiotic use based on infection burden using the WHO AWaRe book guidance. This study developed a framework for estimating required Watch antibiotic use but did not provide comprehensive estimates for Access and Reserve use. Summan et al. (2025) estimated antibiotic needs for chronic obstructive pulmonary disease (COPD) and pneumonia in 20 CTAs using disease burden and bacterial aetiology. These estimates focused only on penicillins and cephalosporins and did not provide population based standardised measures to allow for cross-national comparison among CTAs. Mishra et al. (2025) estimated the gap in Reserve antibiotic treatment courses for use in carbapenem resistant Gram-negative infections in 8 countries using GRAM estimates and IQVIA sales data. While these studies have estimated expected antibiotic use for specific antibiotics or infections, there is no reported method to estimate optimal national levels of total and AWaRe antibiotic use. Added value of this studyWe developed a standard method for deriving optimal ranges of total and AWaRe antibiotic use in defined daily doses (DDD) per 1000 inhabitants per day (DID) accounting for national level infection and antibiotic resistance burden, population socio-demographics, national income, health system infrastructure and healthcare access using a benchmarking approach. Our study provides the first comprehensive estimates of optimal levels of total antibiotic use and disaggregated by AWaRe group in DID for a 2019 baseline for 186 CTAs and compares actual levels of AWaRe use to expected optimal use for 67 CTAs using the IQVIA MIDAS(R) dataset. We used publicly available data from the Global Burden of Disease (GBD), Global Research on Antimicrobial Resistance (GRAM) and the World Bank to provide an open-access, standardised AWaRe-clinical framework that could inform national and global evidence-based antibiotic policy development and implementation. Implications of all the available evidenceAlthough some recent studies have attempted to derive estimates for optimal levels of antibiotic use, they have been focused on specific infections or antibiotics. The UNGA AMR commitments provide a clear direction for global target setting for antibiotic use. Our study provides the first method to estimate optimal antibiotic levels at a country level for both total and AWaRe, based on local infection burden and antibiotic resistance for 186 CTAs. Estimating optimal antibiotic levels with an agreed standard methodology across CTAs would allow for benchmarking and peer-comparison, assisting with target setting and shared learning across National Action Plans from different policy initiatives and outcomes.

New tuberculosis (TB) vaccines for adults and adolescents could transform TB prevention programs, but their impact depends on successful implementation. We investigated willingness to be vaccinated with a new TB vaccine in a high HIV and TB burden setting in southern Mozambique in 2024 using a mixed methods approach involving a cross-sectional survey and concurrent in-depth interviews. In 151 surveys and 23 interviews, we found that willingness to receive a new TB vaccine among adults and adolescents was 77% (148/192) overall. In multivariable analysis, adolescents were more willing to receive a new TB vaccine than adults even when adjusting for other factors which may influence vaccination decisions (adjusted OR: 5.6, 95% CI: 1.7-17.7). Personal experience with TB and greater knowledge of the disease was also linked with willingness to be vaccinated. Qualitative findings reinforced quantitative findings, further clarifying that even among those who expressed hesitancy, a safe and effective TB vaccine endorsed by healthcare workers, government agencies, and community leaders would likely have high uptake. Our findings are specific to southern Mozambique and can shape vaccine introduction efforts after a TB vaccine is licensed and approved for use in this age group.

Antimicrobial resistance (AMR) is classified by the World Health Organization (WHO) as one of humanity's ten global public health threats. This review aimed to estimate the prevalence, temporal trends and regional distribution of AMR in WHO priority bacteria across human, animal and environmental sources in Cameroon. This review was conducted following PRISMA 2020 guidelines, with the protocol registered in PROSPERO. A systematic literature search was conducted in Google Scholar, PubMed, African Journals Online, Hinari, and Africa indexus Medicus. Random effects models were used to estimate pooled prevalence and 95% confidence intervals (CIs), with subgroup analyses by bacterial source, region, and sampling period. Of 1566 articles screened, 115 met the inclusion criteria. The reported data encompassed 16 bacteria-antibiotic combinations in 16,948 isolates. Globally, third-generation cephalosporin (3GC) resistance in E. coli was the most prevalent (49.0%, 95% CI: 39.0-60.0%, I2=97.7%), reaching 77.0% (95% CI: 46.0-98.0%, I2=95.6%) in environmental isolates. The pooled prevalence of ESBL production in all included Enterobacterales was 37.0% (95% CI: 30.0-45.0%). Most of the highest resistance rates were observed in the Littoral region. The resistance rates between 2016 and 2025 were significantly higher than those from 2000 to 2015. These increases were more marked in fluoroquinolone-resistant Salmonella spp (1.0% to 48.0%, I2=97.3%, p<0.001), carbapenem-resistant E. coli (0% to 15%, I2=93.5%, p<0.001), and 3GC-resistant E. coli (34.0% to 64.0%, I2=97.6%, p=0.003). Antimicrobial resistance in WHO priority bacteria in Cameroon is high, unevenly distributed across regions and significantly increasing over time. These results underscore the crucial need for strengthened AMR surveillance to curb the growing threat of AMR in Cameroon.

BackgroundNeisseria gonorrhoeae poses significant public health challenges due to multidrug-resistant gonorrhoeic and severe reproductive health complications of untreated infection. No vaccine is licensed to prevent gonorrhea. However, the meningococcal outer membrane vesicle (OMV)-containing vaccine, 4CMenB, provides moderate cross-protection against gonorrhea. We have recently demonstrated that immunization with gonococcal OMV accelerates clearance of gonococcal infection in mice compared with 4CMenB. MethodsTo gain insight into possible mechanisms of protection of gonococcal OMV, we evaluated the immunogenicity of GonoVac, a candidate native OMV (nOMV) vaccine against gonorrhea, in mice and rabbits. Three doses of GonoVac were administered intramuscularly from 0.15 to 5 {micro}g in mice, and four doses were used to immunize rabbits at 50 {micro}g per dose, formulated with or without aluminum hydroxide (Al(OH)3). Systemic and mucosal antibody responses were evaluated by enzyme-linked immunosorbent assay (ELISA) and serum bactericidal assay (SBA). Cellular responses were assessed by enzyme-linked immunosorbent spot (ELISpot). ResultsImmunization with GonoVac formulated with and without Al(OH)3 induced significantly higher levels of gonococcal serum and vaginal IgG, and serum bactericidal antibodies, compared with 4CMenB, which induced no serum killing activity. Serum bactericidal activity of GonoVac correlated with anti-gonococcal IgG and IgG2a levels. Serum IgA levels were minimal. Cellular immune responses were higher in mice receiving GonoVac/Al(OH)3 compared with GonoVac alone. Immunogenicity was similar for GonoVac produced in a bioreactor and shake flasks. ConclusionGonoVac elicits robust and functional immune responses in mice and rabbits compared with 4CMenB, supporting its further development as a promising candidate vaccine against gonorrhea. ImportanceGonorrhea, caused by Neisseria gonorrhoeae, remains a significant global health concern, disproportionately affecting populations in low- and middle-income countries (LMICs), particularly women. The emergence of multidrug-resistant strains of N. gonorrhoeae has raised the concern of untreatable gonorrhea, underscoring the urgent need for effective preventive measures. Although there is no licensed vaccine against gonorrhea, the meningococcal OMV-based vaccine, 4CMenB, is partially effective against the disease and has been recommended for use in high-risk groups. In this article, we build on previous findings of enhanced efficacy of gonococcal OMV vaccine candidates compared with 4CMenB in the mouse gonococcal infection model to demonstrate the superior anti-gonococcal immunogenicity of a gonococcal OMV-based candidate vaccine (GonoVac) compared with 4CMenB. GonoVac elicits robust immunity in mice, inducing antibodies that are able to kill gonococci, whereas 4CMenB does not. The findings highlight the potential of GonoVac as a promising vaccine candidate for the prevention of gonorrhea worldwide.

BackgroundPeople with HIV (PWH) experience higher cancer-specific mortality and may have worse surgical outcomes than people without HIV (PWoH), though the limited prior evidence largely predates the treat-all antiretroviral therapy (ART) era. We examined postoperative outcomes among PWH and PWoH enrolled in Medicaid in 26 states and Washington, D.C. from 2001-2021. MethodsWe identified the first inpatient/outpatient surgery for anal, bladder, breast, colorectal, female genitourinary, gastroesophageal, head and neck, kidney, liver, lung, ovarian, or pancreatic cancer among adults with continuous enrollment for at least 6 months pre- and 3 months post-surgery. Outcomes included length of stay (LOS), 7- and 30-day readmissions (overall and unplanned), emergency department (ED) use, surgical site infection (SSI), and mortality (30-day, 90-day, 1-year, 5-year). Linear, logistic, and Cox proportional hazards models were adjusted for demographics, comorbidities, cancer type, surgical setting and risk, metastasis, and preoperative treatment (radiation/chemotherapy). ResultsAmong 198,535 beneficiaries undergoing cancer surgery, 4,199 (2.1%) were PWH. PWH were more likely to have inpatient procedures (72.6% vs. 56.4%). Compared to PWoH, PWH had more utilization with longer LOS (7.0 vs. 4.3 days; adjusted mean difference [aMD] = 0.79, 95% CI = 0.60-0.99), extended hospital stays (13.8 vs. 7.4 days; aMD=2.76, 95% CI= 2.42-3.10), and more ED visits (0.82 vs. 0.55 per 90 days; aMD = 0.19, 95% CI = 0.15-0.23). There were no significant differences in readmission, SSI, or 30-day mortality. PWH had higher 90-day mortality (3.2% vs. 1.8%; adjusted odds ratio [aOR] = 1.31, 95% CI = 1.08-1.57), though this was attenuated in the treat-all ART era (2012 - 2021). Results were similar for inpatient surgeries and most common cancer types. PWH had an elevated hazard of 1-year and 5-year mortality post-surgery with an adjusted hazard ratio [aHR] of 1.31 (95% CI = 1.17-1.46) and 1.22 (95% CI= 1.14-1.31), respectively, especially for colorectal cancer (1-year aHR= 1.53, 95% CI=1.24-1.88; 5-year aHR=1.32, 95% CI= 1.14-1.52). ConclusionsPWH had higher post-cancer surgery utilization but similar short-term complications, which supports current guidelines to provide standard cancer care for PWH. More work is needed to elucidate the factors contributing to higher long-term mortality among PWH.

BackgroundMpox virus (MPXV) has caused recurrent outbreaks in West Africa. However, Guinea had not previously reported laboratory-confirmed cases or MPXV genomic data. MethodsSuspected cases were identified in the NZerekore region as well as in the Conakry (Sept 2024- Dec 2025) and confirmed by real-time PCR in regional and central laboratories, respectively. Whole-genome sequencing using nanopore technology was performed in-country, followed by phylogenetic and time-scaled evolutionary analyses. FindingsThe first mpox case was clinically diagnosed in September 2024 in the NZerekore region and laboratory-confirmed by the prefectural laboratory in Gueckedou. In total, seven cases were confirmed in Forest Guinea, of which five complete or almost complete MPXV genomes were recovered. All belonged to MPXV clade IIa. Genomic divergence, ancestral dating, and low APOBEC3-associated mutation frequencies were consistent with multiple independent zoonotic spillover events. In June 2025, one of the first mpox cases of an unfolding outbreak was confirmed in Conakry. Whole genome sequencing revealed MPXV clade IIb lineage G.1. By December 2025, the number of laboratory-confirmed mpox cases nationwide increased to 2,151. A total of nine outbreak strains were sequenced, all belonging to Clade IIb. The genomes clustered with contemporaneous genomes from Sierra Leone and showed high APOBEC3-associated mutation frequencies, suggesting sustained human-to-human transmission in the region. InterpretationThese data demonstrate simultaneous circulation of MPXV clade IIa and IIb strains in Guinea, likely resulting from zoonotic spillover and human-to-human transmission, respectively. Decentralised diagnostics and in-country sequencing facilitated rapid case confirmation and genomic surveillance, highlighting the importance of these critical capacities for outbreak preparedness and response. FundingGerman Federal Ministry of Health and the German Center for Infection Research (DZIF).

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.

ObjectivesCervical cancer is a preventable disease, and a properly implemented screening programme can reduce its incidence and mortality and potentially save resources. This study aimed to evaluate the cost-effectiveness of options for potential transformation of the nationwide screening programme in the Czech Republic, especially considering recent changes in HPV DNA testing recommendations. MethodsA microsimulation model was developed to assess the cost-effectiveness and health benefits of alternative screening strategies in the Czech Republic. The model simulated annual life cycles of women from age 15, comparing combinations of cytology and HPV testing. Input parameters used were obtained from national registries in the Czech Republic and from published literature. The analysis was conducted from the perspective of healthcare payers. Costs (2025 EUR) and LYs were discounted at a rate of 3% annually. Probabilistic sensitivity analysis was conducted. ResultsThe CEA showed that, compared to the current setting (annual cytology with co-test at 35, 45, 55), only specific co-testing strategies lead to a decrease in incidence and mortality but differ in benefits and economic efficiency. The lowest ICER was reported for a strategy combining cytology at two-year intervals and co-testing at four-year intervals from ages 30 to 65. Sensitivity analysis showed that the current strategy has the highest probability of cost-effectiveness at {euro}31,000 per LY gained. At higher values, this is replaced by a strategy with a 3-year interval co-test. ConclusionsBased on the models presented, co-testing appears to be cost-effective. The actual willingness to pay threshold will facilitate selection of the most-appropriate strategy.

PurposeTumor genomic testing (TGT) is standard-of-care for most patients with advanced/metastatic cancer. Despite established guidelines, patient education prior to TGT is frequently omitted. The purpose of this study was to evaluate the impact and durability of a concise 3-4 minute video for patient education prior to TGT in community versus academic sites and across cancer types. Patients and MethodsPatients undergoing standard-of-care TGT were enrolled at a tertiary academic institution in three cohorts: Cohort 1-breast cancer; Cohort 2-lung cancer; Cohort 3-other cancers. Cohort 4 consisted of patients with any cancer type similarly undergoing SOC TGT at one of three community cancer centers. Participants completed survey measures prior to video viewing (T1), immediately post-viewing (T2), and after return of TGT results (T3). Outcome measures included: 1) 10-question objective genomic knowledge/understanding (GKU); 2) 10-question video message-specific knowledge (VMSK); 3) 11-question Trust in Physician/Provider (TIPP); 4) perceptions regarding TGT. ResultsA total of 203 participants completed all survey timepoints. Higher baseline GKU and VMSK scores were significantly associated with higher income and greater years of education. For the primary objective, there was a significant and sustained improvement in VMSK from T1:T2:T3 (Poverall p<0.0001), with no significant change in GKU (p=0.41) or TIPP (p=0.73). This trend was consistent within each cohort (all p[&le;]0.0001). Results for four VMSK questions significantly improved, including impact on treatment decisions, incidental germline findings, and insurance coverage of testing. ConclusionsA concise, 3-4 minute, broadly applicable educational video administered prior to TGT significantly and sustainably improved video message-specific knowledge in diverse cancer types and in academic and community settings. This resource is publicly available at http://www.tumor-testing.com, with a goal to efficiently educate and empower patients regarding TGT while addressing guidelines within the flow of clinical practice.