Background: Cancer is a leading cause of death globally. Accurate cancer burden information is crucial for policy planning, but many countries do not have up-to-date cancer surveillance data. To inform global cancer-control efforts, we used the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 framework to generate and analyse estimates of cancer burden for 47 cancer types or groupings by age, sex, and 204 countries and territories from 1990 to 2023, cancer burden attributable to selected risk factors from 1990 to 2023, and forecasted cancer burden up to 2050. Methods: Cancer estimation in GBD 2023 used data from population-based cancer registration systems, vital registration systems, and verbal autopsies. Cancer mortality was estimated using ensemble models, with incidence informed by mortality estimates and mortality-to-incidence ratios (MIRs). Prevalence estimates were generated from modelled survival estimates, then multiplied by disability weights to estimate years lived with disability (YLDs). Years of life lost (YLLs) were estimated by multiplying age-specific cancer deaths by the GBD standard life expectancy at the age of death. Disability-adjusted life-years (DALYs) were calculated as the sum of YLLs and YLDs. We used the GBD 2023 comparative risk assessment framework to estimate cancer burden attributable to 44 behavioural, environmental and occupational, and metabolic risk factors. To forecast cancer burden from 2024 to 2050, we used the GBD 2023 forecasting framework, which included forecasts of relevant risk factor exposures and used Socio-demographic Index as a covariate for forecasting the proportion of each cancer not affected by these risk factors. Progress towards the UN Sustainable Development Goal (SDG) target 3.4 aim to reduce non-communicable disease mortality by a third between 2015 and 2030 was estimated for cancer. Findings: In 2023, excluding non-melanoma skin cancers, there were 18·5 million (95% uncertainty interval 16·4 to 20·7) incident cases of cancer and 10·4 million (9·65 to 10·9) deaths, contributing to 271 million (255 to 285) DALYs globally. Of these, 57·9% (56·1 to 59·8) of incident cases and 65·8% (64·3 to 67·6) of cancer deaths occurred in low-income to upper-middle-income countries based on World Bank income group classifications. Cancer was the second leading cause of deaths globally in 2023 after cardiovascular diseases. There were 4·33 million (3·85 to 4·78) risk-attributable cancer deaths globally in 2023, comprising 41·7% (37·8 to 45·4) of all cancer deaths. Risk-attributable cancer deaths increased by 72·3% (57·1 to 86·8) from 1990 to 2023, whereas overall global cancer deaths increased by 74·3% (62·2 to 86·2) over the same period. The reference forecasts (the most likely future) estimate that in 2050 there will be 30·5 million (22·9 to 38·9) cases and 18·6 million (15·6 to 21·5) deaths from cancer globally, 60·7% (41·9 to 80·6) and 74·5% (50·1 to 104·2) increases from 2024, respectively. These forecasted increases in deaths are greater in low-income and middle-income countries (90·6% [61·0 to 127·0]) compared with high-income countries (42·8% [28·3 to 58·6]). Most of these increases are likely due to demographic changes, as age-standardised death rates are forecast to change by –5·6% (–12·8 to 4·6) between 2024 and 2050 globally. Between 2015 and 2030, the probability of dying due to cancer between the ages of 30 years and 70 years was forecasted to have a relative decrease of 6·5% (3·2 to 10·3). Interpretation: Cancer is a major contributor to global disease burden, with increasing numbers of cases and deaths forecasted up to 2050 and a disproportionate growth in burden in countries with scarce resources. The decline in age-standardised mortality rates from cancer is encouraging but insufficient to meet the SDG target set for 2030. Effectively and sustainably addressing cancer burden globally will require comprehensive national and international efforts that consider health systems and context in the development and implementation of cancer-control strategies across the continuum of prevention, diagnosis, and treatment. Funding: Gates Foundation, St Jude Children's Research Hospital, and St Baldrick's Foundation.

Background Chronic kidney disease (CKD) is common and ranks among the leading causes of mortality and morbidity. This analysis aimed to present global CKD estimates using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 to inform evidence-based policies for CKD identification and treatment. Methods This analysis focused on adults aged 20 years and older over the period 1990 to 2023, from 204 countries and territories. Data sources used were published literature, vital registration systems, kidney failure treatment registries, and household surveys. Estimates of CKD burden, including deaths, incidence, prevalence, and disability-adjusted life-years (DALYs), were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool. A comparative risk assessment approach estimated the proportion of cardiovascular deaths attributable to impaired kidney function and estimated risk factors for CKD. Findings Globally, in 2023, 788 million (95% uncertainty interval 743–843) people aged 20 years and older were estimated to have CKD, up from 378 million (354–407) in 1990. The global age-standardised prevalence of CKD in adults was 14·2% (13·4–15·2), a relative rise of 3·5% (2·7–4·1) from 1990. The region with the highest age-standardised prevalence was north Africa and the Middle East (18·0%; 16·9–19·4). Most people had stage 1–3 CKD, with a combined prevalence of 13·9% (13·1–15·0). In 2023, CKD was the ninth leading cause of death globally, accounting for 1·48 million (1·30–1·65) deaths, and the 12th leading cause of DALYs, with an age-standardised DALY rate of 769·2 (691·8–857·4) per 100 000. Impaired kidney function as a risk factor accounted for 11·5% (8·4–14·5) of cardiovascular deaths. High fasting plasma glucose, body-mass index, and systolic blood pressure were all leading risk factors for CKD DALYs. Interpretation CKD is a major global health issue, with rising prevalence and increasing importance as a cause of death and as a risk factor for cardiovascular death. A better understating of aetiology, appropriate screening, and implementation programmes are needed to translate advances in CKD treatment into improved patient outcomes. Funding Gates Foundation, Wellcome, US National Kidney Foundation, and US National Institute of Diabetes and Digestive and Kidney Diseases.

ORFV, also known as Ecthyma contagiosum, in humans is the Orf virus (ORFV), which mostly infects various wild and domesticated animals. A highly contagious zoonotic viral infection is a major concern to everyone who works with sheep and goats. According to taxonomy, ORFV belongs to the genus Parapoxvirus. People encounter animals, their exposed skin areas usually develop sores. Even though the quantity of infected individuals and appearances are thought to be less dangerous, the pathogenic virus's high fatality rate is still a serious concern. Vaccine construct There is currently no approved vaccine to lessen the epidemiological and clinical burden of this highly contagious illness. Thus, the target proteins of ORFV are used in our current investigation to design and formulate a multi-epitope vaccination using immunoinformatic approaches. Potential T-cell and B-cell epitopes from the two pathogenic proteins of ORFV were tested using selection criteria. The chosen epitopes were then put together using the appropriate adjuvants and linkers. MHC cluster analysis and population coverage of the chosen epitopes were both satisfactory. To maintain the tertiary or quaternary relationships, we used disulfide bonding engineering. Additionally, normal-mode analysis was used to investigate the vaccine protein stability and kinematics. The immunological simulation research of vaccine complexes also yielded substantial findings. Furthermore, the molecular docking demonstrated a greater affinity of −265.85 kcal/mol for toll-like receptor-4 (TLR4). Molecular dynamics simulations resulted in the stability of the complex system with (mean RMSD: 7.7 Å; Rg: 18.6 Å), exhibiting localized flexibility at certain residues. Calculations of binding free energy (ΔG = −456.67 kcal/mol, GBSA; −469.56 kcal/mol, PBSA) indicated highly favorable and spontaneous interactions facilitated by electrostatic and van der Waals forces. Herein, our research findings revealed that the vaccine designs may modulate encouraging immune responses against the pathophysiology of ORFV. Therefore, it can generate a baseline pipeline for the experimentalist for in vivo and in vitro investigations.

Background: Lower respiratory infections (LRIs) remain the world's leading infectious cause of death. This analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides global, regional, and national estimates of LRI incidence, mortality, and disability-adjusted life-years (DALYs), with attribution to 26 pathogens, including 11 newly modelled pathogens, across 204 countries and territories from 1990 to 2023. With new data and revised modelling techniques, these estimates serve as an update and expansion to GBD 2021. Through these estimates, we also aimed to assess progress towards the 2025 Global Action Plan for the Prevention and Control of Pneumonia and Diarrhoea (GAPPD) target for pneumonia mortality in children younger than 5 years. Methods: Mortality from LRIs, defined as physician-diagnosed pneumonia or bronchiolitis, was estimated using the Cause of Death Ensemble model with data from vital registration, verbal autopsy, surveillance, and minimally invasive tissue sampling. The Bayesian meta-regression tool DisMod-MR 2.1 was used to model overall morbidity due to LRIs. DALYs were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs) for all locations, years, age groups, and sexes. We modelled pathogen-specific case-fatality ratios (CFRs) for each age group and location using splined binomial regression to create internally consistent estimates of incidence and mortality proportions attributable to viral, fungal, parasitic, and bacterial pathogens. Progress was assessed towards the GAPPD target of less than three deaths from pneumonia per 1000 livebirths, which is roughly equivalent to a mortality rate of less than 60 deaths per 100 000 children younger than 5 years. Findings: In 2023, LRIs were responsible for 2·50 million (95% uncertainty interval [UI] 2·24–2·81) deaths and 98·7 million (87·7–112) DALYs, with children younger than 5 years and adults aged 70 years and older carrying the highest burden. LRI mortality in children younger than 5 years fell by 33·4% (10·4–47·4) since 2010, with a global mortality rate of 94·8 (75·6–116·4) per 100 000 person-years in 2023. Among adults aged 70 years and older, the burden remained substantial with only marginal declines since 2010. A mortality rate of less than 60 deaths per 100 000 for children younger than 5 years was met by 129 of the 204 modelled countries in 2023. At a super-regional level, sub-Saharan Africa had an aggregate mortality rate in children younger than 5 years (hereafter referred to as under-5 mortality rate) furthest from the GAPPD target. Streptococcus pneumoniae continued to account for the largest number of LRI deaths globally (634 000 [95% UI 565 000–721 000] deaths or 25·3% [24·5–26·1] of all LRI deaths), followed by Staphylococcus aureus (271 000 [243 000–298 000] deaths or 10·9% [10·3–11·3]), and Klebsiella pneumoniae (228 000 [204 000–261 000] deaths or 9·1% [8·8–9·5]). Among pathogens newly modelled in this study, non-tuberculous mycobacteria (responsible for 177 000 [95% UI 155 000–201 000] deaths) and Aspergillus spp (responsible for 67 800 [59 900–75 900] deaths) emerged as important contributors. Altogether, the 11 newly modelled pathogens accounted for approximately 22% of LRI deaths. Interpretation: This comprehensive analysis underscores both the gains achieved through vaccination and the challenges that remain in controlling the LRI burden globally. Furthermore, it demonstrates persistent disparities in disease burden, with the highest mortality rates concentrated in countries in sub-Saharan Africa. Globally, as well as in these high-burden locations, the under-5 LRI mortality rate remains well above the GAPPD target. Progress towards this target requires equitable access to vaccines and preventive therapies—including newer interventions such as respiratory syncytial virus monoclonal antibodies—and health systems capable of early diagnosis and treatment. Expanding surveillance of emerging pathogens, strengthening adult immunisation programmes, and combating vaccine hesitancy are also crucial. As the global population ages, the dual challenge of sustaining gains in child survival while addressing the rising vulnerability in older adults will shape future pneumonia control strategies. Funding: Gates Foundation.

Background: Chronic respiratory diseases are an important global issue, particularly in Asia, where burden patterns vary widely across countries. With more than half the world's population living in Asia, understanding the national and regional burden of chronic respiratory diseases is essential; however, research on this area remains inadequate. We aimed to investigate the burden of chronic respiratory diseases in Asia at national and regional levels, and to identify key risk factors. Methods: The Global Burden of Diseases, Injuries, and Risk Factors Study 2023 provides estimates for assessing the burden of chronic respiratory diseases, including chronic obstructive pulmonary disease (COPD), asthma, pneumoconiosis, interstitial lung disease (ILD), and pulmonary sarcoidosis. We focused on 34 countries in Asia, encompassing the high-income Asia Pacific region and central, east, south, and southeast Asia. Estimates for age-standardised prevalence and disability-adjusted life-year (DALY) rates per 100 000 population, including 95% uncertainty intervals (UIs), were extracted by location, sex, year, and Socio-demographic Index (SDI). The average annual percentage change was calculated and presented as a percentage with 95% CIs. Estimates of modifiable attributable risk factors for DALYs and mortality were also included. Findings: In Asia, the age-standardised prevalence and DALY rates for chronic respiratory diseases generally declined from 1990 to 2023; however, the trend varied substantially by disease and country. In 2023, the age-standardised prevalence rate of COPD was highest in south Asia (3044·18 [95% UI 2748·67–3303·04] per 100 000 population), while the age-standardised asthma prevalence rate was highest in the high-income Asia Pacific region (4870·24 [4046·70–5962·78] per 100 000 population) and southeast Asia (4778·18 [3970·25–5735·61] per 100 000 population). Despite southeast Asia and the high-income Asia Pacific region having a similar age-standardised asthma prevalence rate, southeast Asia had a higher age-standardised DALY rate (508·67 [95% UI 394·89–669·92] per 100 000 population) compared with the high-income Asia Pacific region (204·40 [129·23–290·41] per 100 000 population). A decrease in the age-standardised DALY rate for chronic respiratory diseases was observed with increasing SDI, contrasting with its prevalence patterns. Age-standardised DALY rates of COPD decreased in all Asian countries except for Georgia (average annual percentage change 1·37 [95% CI 1·26–1·48]) and Kazakhstan (0·73 [0·55–0·93]), and age-standardised DALY rates of asthma decreased in all countries. Smoking and ambient particulate matter pollution were identified as leading attributable risk factors for chronic respiratory diseases across Asia. Household air pollution from solid fuels was a regionally pronounced risk factor for chronic respiratory diseases, particularly in south Asia (age-standardised DALY rate 657·58 [95% UI 485·04–880·45] per 100 000 population). Although smoking was a major risk factor in males, ambient particulate matter pollution and secondhand smoke emerged as important attributable risk factors for chronic respiratory diseases in females. Interpretation: Countries with lower SDI had markedly higher DALY rates, highlighting the need to address socioeconomic and health-care inequities. Household air pollution from solid fuels continues to impose a substantial but preventable burden in south Asia, calling for clean energy adoption and improved ventilation. Funding: Gates Foundation.

Background: Meningitis remains the leading infectious cause of neurological disabilities globally, disproportionately affecting children younger than 5 years and populations in the African meningitis belt. Whereas previous global estimates focused on ten pathogen categories, this study presents the most comprehensive analysis to date, assessing the meningitis burden attributable to 17 causative pathogens based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 framework. Methods: GBD is a systematic, scientific effort aimed at quantifying the comparative magnitude of health loss caused by diseases, injuries, and risk factors across age groups, sexes, and geographical locations over time. We estimated meningitis mortality using the Cause of Death Ensemble model (CODEm) and morbidity using DisMod-MR 2.1, incorporating data from vital registration, verbal autopsy, surveillance, hospital data, and systematic reviews. Aetiology-specific estimates were generated with pathogen-linked case-fatality ratios and splined binomial regression models. Risk factor attribution was based on established risk–outcome pairs and population attributable fractions. Findings: In 2023, there were 259 000 (95% uncertainty interval 202 000–335 000) global deaths and 2·54 million (2·20–2·93) incident cases of meningitis. Children younger than 5 years accounted for more than a third of deaths (86 600 [53 300–149 000]). Streptococcus pneumoniae, Neisseria meningitidis, non-polio enteroviruses, and other viruses were the leading causes of death, while non-polio enteroviruses caused the most cases. The four WHO-defined preventable meningitis pathogens of interest (S pneumoniae, N meningitidis, Haemophilus influenzae, and Group B streptococcus) contributed to 98 700 deaths (77 000–127 000) and 594 000 cases (514 000–686 000). Low birthweight, short gestation, and household air pollution were the top risk factors for meningitis-related mortality. Interpretation: Although mortality and incidence have declined significantly since 1990, progress is insufficient to meet WHO 2030 targets. Despite marked progress in reducing bacterial meningitis via global vaccination campaigns, a substantial meningitis burden persists, attributable both to common pathogens such as S pneumoniae and N meningitidis and to emerging non-bacterial pathogens such as Candida spp and drug-resistant fungi. Achieving WHO goals will require sustained investment in surveillance, vaccination, maternal screening, and health-system strengthening, especially in high-burden settings. Funding: Gates Foundation, Wellcome Trust, and UK Department of Health and Social Care.

Background The 2023 iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated prevalence, incidence, and health burden for 375 diseases and injuries, including 12 mental disorders. We assess past, current, and emerging trends in the prevalence and burden of mental disorders across sexes and age groups, for 21 regions, 204 countries and territories, and by Socio-demographic Index (SDI) quintile, from 1990 to 2023. Methods Mental disorders included in GBD 2023 were anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, anorexia nervosa, bulimia nervosa, idiopathic developmental intellectual disability, and a residual category of other mental disorders. A literature review identified epidemiological data for each disorder. These were analysed via a Bayesian meta-regression to estimate prevalence by disorder, sex, age, location, and year. Disorder-specific prevalence was multiplied by disability weights representing the severity of health loss associated with each disorder to estimate years lived with disability (YLDs). Deaths due to anorexia nervosa were assessed with a Cause of Death Ensemble modelling strategy to estimate deaths by sex, age, location, and year, and then multiplied by the standard life expectancy at age of death to estimate years of life lost (YLLs). YLDs equalled disability-adjusted life-years (DALYs) for all mental disorders except anorexia nervosa (the only mental disorder considered as an underlying cause of death in GBD), for which DALYs represented the sum of YLDs and YLLs. We presented prevalence, deaths, YLDs, YLLs, and DALYs as counts, age-specific rates per 100 000 population, and age-standardised rates per 100 000 population. Findings We estimated 1·17 billion (95% uncertainty interval 1·06–1·31) prevalent cases of mental disorders globally in 2023, equivalent to an age-standardised prevalence rate of 14 210·7 cases (12 849·5–15 940·1) per 100 000 population. These estimates represented a 95·5% (75·0–121·2) increase in prevalent cases and 24·2% (11·4–41·4) increase in age-standardised prevalence rate between 1990 and 2023. All mental disorders showed increases in prevalent cases between 1990 and 2023, while notable increases were seen in age-standardised prevalence rates for anxiety disorders, major depressive disorder, dysthymia, anorexia nervosa, bulimia nervosa, schizophrenia, and conduct disorder. There were an estimated 171 million (127–228) DALYs due to mental disorders globally across sex and age in 2023, equivalent to an age-standardised DALY rate of 2070·5 DALYs (1519·1–2750·5) per 100 000 population. Mental disorders contributed to 6·1% (4·8–7·6) of all-cause DALYs in 2023, making them the fifth leading cause of global DALYs (up from 12th in 1990). DALYs were almost entirely composed of YLDs. Mental disorders were the leading cause of YLDs in 2023 (up from second in 1990), explaining 17·3% (14·8–20·6) of all-cause global YLDs. Leading causes of mental disorder DALYs were anxiety disorders (ranked 11th among the 304 diseases and injuries at Level 4 of the GBD cause hierarchy), major depressive disorder (15th), and schizophrenia (41st). Globally in 2023, mental disorder age-standardised DALY rates were higher among females (2239·6 [1643·7–3014·1] per 100 000) than among males (1900·2 [1399·8–2510·8] per 100 000), and peaked in the 15–19 years age group (2617·3 [1850·6–3696·8] per 100 000). All locations showed increased mental disorder DALY rates in 2023 compared with 1990, ranging across countries and territories from 1302·4 (952·7–1683·7) per 100 000 in Viet Nam to 3555·8 (2661·9–4715·0) per 100 000 in the Netherlands. Across SDI quintiles, DALY rates ranged from 1853·0 (1352·1–2469·3) per 100 000 for middle SDI to 2184·1 (1606·1–2890·3) per 100 000 for high SDI. Interpretation A significant health burden was imposed by mental disorders in all countries and territories in 2023, irrespective of the health resources available. In some instances, this burden has increased over time and is unevenly distributed across populations. Stronger surveillance systems, particularly in low-income and middle-income countries, are required. Additionally, we need more coordinated and inclusive policies to reduce the burden through early treatment and prevention, tailored to sex and age differences across locations. Responding to the mental health needs of our global population, especially those most vulnerable, is an obligation, not a choice. Funding Gates Foundation, Queensland Health, and University of Queensland.