Background: Since its inception in 1974, the Essential Programme on Immunization (EPI) has achieved remarkable success, averting the deaths of an estimated 154 million children worldwide through routine childhood vaccination. However, more recent decades have seen persistent coverage inequities and stagnating progress, which have been further amplified by the COVID-19 pandemic. In 2019, WHO set ambitious goals for improving vaccine coverage globally through the Immunization Agenda 2030 (IA2030). Now halfway through the decade, understanding past and recent coverage trends can help inform and reorient strategies for approaching these aims in the next 5 years. Methods: Based on the Global Burden of Diseases, Injuries, and Risk Factors Study 2023, this study provides updated global, regional, and national estimates of routine childhood vaccine coverage from 1980 to 2023 for 204 countries and territories for 11 vaccine-dose combinations recommended by WHO for all children globally. Employing advanced modelling techniques, this analysis accounts for data biases and heterogeneity and integrates new methodologies to model vaccine scale-up and COVID-19 pandemic-related disruptions. To contextualise historic coverage trends and gains still needed to achieve the IA2030 coverage targets, we supplement these results with several secondary analyses: (1) we assess the effect of the COVID-19 pandemic on vaccine coverage; (2) we forecast coverage of select life-course vaccines up to 2030; and (3) we analyse progress needed to reduce the number of zero-dose children by half between 2023 and 2030. Findings: Overall, global coverage for the original EPI vaccines against diphtheria, tetanus, and pertussis (first dose [DTP1] and third dose [DTP3]), measles (MCV1), polio (Pol3), and tuberculosis (BCG) nearly doubled from 1980 to 2023. However, this long-term trend masks recent challenges. Coverage gains slowed between 2010 and 2019 in many countries and territories, including declines in 21 of 36 high-income countries and territories for at least one of these vaccine doses (excluding BCG, which has been removed from routine immunisation schedules in some countries and territories). The COVID-19 pandemic exacerbated these challenges, with global rates for these vaccines declining sharply since 2020, and still not returning to pre-COVID-19 pandemic levels as of 2023. Coverage for newer vaccines developed and introduced in more recent years, such as immunisations against pneumococcal disease (PCV3) and rotavirus (complete series; RotaC) and a second dose of the measles vaccine (MCV2), saw continued increases globally during the COVID-19 pandemic due to ongoing introductions and scale-ups, but at slower rates than expected in the absence of the pandemic. Forecasts to 2030 for DTP3, PCV3, and MCV2 suggest that only DTP3 would reach the IA2030 target of 90% global coverage, and only under an optimistic scenario. The number of zero-dose children, proxied as children younger than 1 year who do not receive DTP1, decreased by 74·9% (95% uncertainty interval 72·1–77·3) globally between 1980 and 2019, with most of those declines reached during the 1980s and the 2000s. After 2019, counts of zero-dose children rose to a COVID 19-era peak of 18·6 million (17·6–20·0) in 2021. Most zero-dose children remain concentrated in conflict-affected regions and those with various constraints on resources available to put towards vaccination services, particularly sub-Saharan Africa. As of 2023, more than 50% of the 15·7 million (14·6–17·0) global zero-dose children resided in just eight countries (Nigeria, India, Democratic Republic of the Congo, Ethiopia, Somalia, Sudan, Indonesia, and Brazil), emphasising persistent inequities. Interpretation: Our estimates of current vaccine coverage and forecasts to 2030 suggest that achieving IA2030 targets, such as halving zero-dose children compared with 2019 levels and reaching 90% global coverage for life-course vaccines DTP3, PCV3, and MCV2, will require accelerated progress. Substantial increases in coverage are necessary in many countries and territories, with those in sub-Saharan Africa and south Asia facing the greatest challenges. Recent declines will need to be reversed to restore previous coverage levels in Latin America and the Caribbean, especially for DTP1, DTP3, and Pol3. These findings underscore the crucial need for targeted, equitable immunisation strategies. Strengthening primary health-care systems, addressing vaccine misinformation and hesitancy, and adapting to local contexts are essential to advancing coverage. COVID-19 pandemic recovery efforts, such as WHO's Big Catch-Up, as well as efforts to bolster routine services must prioritise reaching marginalised populations and target subnational geographies to regain lost ground and achieve global immunisation goals. Funding: The Bill & Melinda Gates Foundation and Gavi, the Vaccine Alliance.

Comprehensive, comparable, and timely estimates of demographic metrics—including life expectancy and age-specific mortality—are essential for evaluating, understanding, and addressing trends in population health. The COVID-19 pandemic highlighted the importance of timely and all-cause mortality estimates for being able to respond to changing trends in health outcomes, showing a strong need for demographic analysis tools that can produce all-cause mortality estimates more rapidly with more readily available all-age vital registration (VR) data. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) is an ongoing research effort that quantifies human health by estimating a range of epidemiological quantities of interest across time, age, sex, location, cause, and risk. This study—part of the latest GBD release, GBD 2023—aims to provide new and updated estimates of all-cause mortality and life expectancy for 1950 to 2023 using a novel statistical model that accounts for complex correlation structures in demographic data across age and time. We used 24 025 data sources from VR, sample registration, surveys, censuses, and other sources to estimate all-cause mortality for males, females, and all sexes combined across 25 age groups in 204 countries and territories as well as 660 subnational units in 20 countries and territories, for the years 1950–2023. For the first time, we used complete birth history data for ages 5–14 years, age-specific sibling history data for ages 15–49 years, and age-specific mortality data from Health and Demographic Surveillance Systems. We developed a single statistical model that incorporates both parametric and non-parametric methods, referred to as OneMod, to produce estimates of all-cause mortality for each age-sex-location group. OneMod includes two main steps: a detailed regression analysis with a generalised linear modelling tool that accounts for age-specific covariate effects such as the Socio-demographic Index (SDI) and a population attributable fraction (PAF) for all risk factors combined; and a non-parametric analysis of residuals using a multivariate kernel regression model that smooths across age and time to adaptably follow trends in the data without overfitting. We calibrated asymptotic uncertainty estimates using Pearson residuals to produce 95% uncertainty intervals (UIs) and corresponding 1000 draws. Life expectancy was calculated from age-specific mortality rates with standard demographic methods. For each measure, 95% UIs were calculated with the 25th and 975th ordered values from a 1000-draw posterior distribution. In 2023, 60·1 million (95% UI 59·0–61·1) deaths occurred globally, of which 4·67 million (4·59–4·75) were in children younger than 5 years. Due to considerable population growth and ageing since 1950, the number of annual deaths globally increased by 35·2% (32·2–38·4) over the 1950–2023 study period, during which the global age-standardised all-cause mortality rate declined by 66·6% (65·8–67·3). Trends in age-specific mortality rates between 2011 and 2023 varied by age group and location, with the largest decline in under-5 mortality occurring in east Asia (67·7% decrease); the largest increases in mortality for those aged 5–14 years, 25–29 years, and 30–39 years occurring in high-income North America (11·5%, 31·7%, and 49·9%, respectively); and the largest increases in mortality for those aged 15–19 years and 20–24 years occurring in Eastern Europe (53·9% and 40·1%, respectively). We also identified higher than previously estimated mortality rates in sub-Saharan Africa for all sexes combined aged 5–14 years (87·3% higher in GBD 2023 than GBD 2021 on average across countries and territories over the 1950–2021 period) and for females aged 15–29 years (61·2% higher), as well as lower than previously estimated mortality rates in sub-Saharan Africa for all sexes combined aged 50 years and older (13·2% lower), reflecting advances in our modelling approach. Global life expectancy followed three distinct trends over the study period. First, between 1950 and 2019, there were considerable improvements, from 51·2 (50·6–51·7) years for females and 47·9 (47·4–48·4) years for males in 1950 to 76·3 (76·2–76·4) years for females and 71·4 (71·3–71·5) years for males in 2019. Second, this period was followed by a decrease in life expectancy during the COVID-19 pandemic, to 74·7 (74·6–74·8) years for females and 69·3 (69·2–69·4) years for males in 2021. Finally, the world experienced a period of post-pandemic recovery in 2022 and 2023, wherein life expectancy generally returned to pre-pandemic (2019) levels in 2023 (76·3 [76·0–76·6] years for females and 71·5 [71·2–71·8] years for males). 194 (95·1%) of 204 countries and territories experienced at least partial post-pandemic recovery in age-standardised mortality rates by 2023, with 61·8% (126 of 204) recovering to or falling below pre-pandemic levels. There were several mortality trajectories during and following the pandemic across countries and territories. Long-term mortality trends also varied considerably between age groups and locations, demonstrating the diverse landscape of health outcomes globally. This analysis identified several key differences in mortality trends from previous estimates, including higher rates of adolescent mortality, higher rates of young adult mortality in females, and lower rates of mortality in older age groups in much of sub-Saharan Africa. The findings also highlight stark differences across countries and territories in the timing and scale of changes in all-cause mortality trends during and following the COVID-19 pandemic (2020–23). Our estimates of evolving trends in mortality and life expectancy across locations, ages, sexes, and SDI levels in recent years as well as over the entire 1950–2023 study period provide crucial information for governments, policy makers, and the public to ensure that health-care systems, economies, and societies are prepared to address the world's health needs, particularly in populations with higher rates of mortality than previously known. The estimates from this study provide a robust framework for GBD and a valuable foundation for policy development, implementation, and evaluation around the world. Gates Foundation.

Background Timely and comprehensive analyses of causes of death stratified by age, sex, and location are essential for shaping effective health policies aimed at reducing global mortality. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides cause-specific mortality estimates measured in counts, rates, and years of life lost (YLLs). GBD 2023 aimed to enhance our understanding of the relationship between age and cause of death by quantifying the probability of dying before age 70 years (70q0) and the mean age at death by cause and sex. This study enables comparisons of the impact of causes of death over time, offering a deeper understanding of how these causes affect global populations. Methods GBD 2023 produced estimates for 292 causes of death disaggregated by age-sex-location-year in 204 countries and territories and 660 subnational locations for each year from 1990 until 2023. We used a modelling tool developed for GBD, the Cause of Death Ensemble model (CODEm), to estimate cause-specific death rates for most causes. We computed YLLs as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. Probability of death was calculated as the chance of dying from a given cause in a specific age period, for a specific population. Mean age at death was calculated by first assigning the midpoint age of each age group for every death, followed by computing the mean of all midpoint ages across all deaths attributed to a given cause. We used GBD death estimates to calculate the observed mean age at death and to model the expected mean age across causes, sexes, years, and locations. The expected mean age reflects the expected mean age at death for individuals within a population, based on global mortality rates and the population's age structure. Comparatively, the observed mean age represents the actual mean age at death, influenced by all factors unique to a location-specific population, including its age structure. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 250-draw distribution for each metric. Findings are reported as counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2023 include a correction for the misclassification of deaths due to COVID-19, updates to the method used to estimate COVID-19, and updates to the CODEm modelling framework. This analysis used 55 761 data sources, including vital registration and verbal autopsy data as well as data from surveys, censuses, surveillance systems, and cancer registries, among others. For GBD 2023, there were 312 new country-years of vital registration cause-of-death data, 3 country-years of surveillance data, 51 country-years of verbal autopsy data, and 144 country-years of other data types that were added to those used in previous GBD rounds. Findings The initial years of the COVID-19 pandemic caused shifts in long-standing rankings of the leading causes of global deaths: it ranked as the number one age-standardised cause of death at Level 3 of the GBD cause classification hierarchy in 2021. By 2023, COVID-19 dropped to the 20th place among the leading global causes, returning the rankings of the leading two causes to those typical across the time series (ie, ischaemic heart disease and stroke). While ischaemic heart disease and stroke persist as leading causes of death, there has been progress in reducing their age-standardised mortality rates globally. Four other leading causes have also shown large declines in global age-standardised mortality rates across the study period: diarrhoeal diseases, tuberculosis, stomach cancer, and measles. Other causes of death showed disparate patterns between sexes, notably for deaths from conflict and terrorism in some locations. A large reduction in age-standardised rates of YLLs occurred for neonatal disorders. Despite this, neonatal disorders remained the leading cause of global YLLs over the period studied, except in 2021, when COVID-19 was temporarily the leading cause. Compared to 1990, there has been a considerable reduction in total YLLs in many vaccine-preventable diseases, most notably diphtheria, pertussis, tetanus, and measles. In addition, this study quantified the mean age at death for all-cause mortality and cause-specific mortality and found noticeable variation by sex and location. The global all-cause mean age at death increased from 46·8 years (95% UI 46·6–47·0) in 1990 to 63·4 years (63·1–63·7) in 2023. For males, mean age increased from 45·4 years (45·1–45·7) to 61·2 years (60·7–61·6), and for females it increased from 48·5 years (48·1–48·8) to 65·9 years (65·5–66·3), from 1990 to 2023. The highest all-cause mean age at death in 2023 was found in the high-income super-region, where the mean age for females reached 80·9 years (80·9–81·0) and for males 74·8 years (74·8–74·9). By comparison, the lowest all-cause mean age at death occurred in sub-Saharan Africa, where it was 38·0 years (37·5–38·4) for females and 35·6 years (35·2–35·9) for males in 2023. Lastly, our study found that all-cause 70q0 decreased across each GBD super-region and region from 2000 to 2023, although with large variability between them. For females, we found that 70q0 notably increased from drug use disorders and conflict and terrorism. Leading causes that increased 70q0 for males also included drug use disorders, as well as diabetes. In sub-Saharan Africa, there was an increase in 70q0 for many non-communicable diseases (NCDs). Additionally, the mean age at death from NCDs was lower than the expected mean age at death for this super-region. By comparison, there was an increase in 70q0 for drug use disorders in the high-income super-region, which also had an observed mean age at death lower than the expected value. Interpretation We examined global mortality patterns over the past three decades, highlighting—with enhanced estimation methods—the impacts of major events such as the COVID-19 pandemic, in addition to broader trends such as increasing NCDs in low-income regions that reflect ongoing shifts in the global epidemiological transition. This study also delves into premature mortality patterns, exploring the interplay between age and causes of death and deepening our understanding of where targeted resources could be applied to further reduce preventable sources of mortality. We provide essential insights into global and regional health disparities, identifying locations in need of targeted interventions to address both communicable and non-communicable diseases. There is an ever-present need for strengthened health-care systems that are resilient to future pandemics and the shifting burden of disease, particularly among ageing populations in regions with high mortality rates. Robust estimates of causes of death are increasingly essential to inform health priorities and guide efforts toward achieving global health equity. The need for global collaboration to reduce preventable mortality is more important than ever, as shifting burdens of disease are affecting all nations, albeit at different paces and scales. Funding Gates Foundation.

Background Antimicrobial resistance (AMR) is an urgent global crisis and one of the world's most complex challenges. Although there is increasing evidence of its impact on human mortality and morbidity, precise burden estimation has many challenges, and thus far has been elusive for the Eastern Mediterranean Region. Here, we present a comprehensive time-trend analysis of regional and country-level AMR burden estimates in the WHO Eastern Mediterranean Region (EMR), between 1990 and 2021, with forecasts up to 2050. Methods We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with AMR for 11 infectious syndromes, 22 bacterial pathogens, and 84 pathogen–drug combinations for the WHO EMR and each of its countries from 1990 to 2021. Data were obtained from mortality registries, surveillance systems, hospital records, systematic literature reviews, and other sources. We based our modelling approach on five broad components: the number of deaths in which infection had a role, the proportion of infectious deaths attributable to a given infectious syndrome, the proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antimicrobial drug of interest, and the excess risk of mortality (or duration of an infection) associated with this resistance. These components were then used to estimate the disease burden by using two counterfactual scenarios: deaths and DALYs attributable to AMR (considering an alternative scenario where drug-resistant infections are replaced with susceptible infections), and deaths and DALYs associated with AMR (considering an alternative scenario where infections would not occur at all). Predictive statistical modelling was applied to generate estimates of AMR burden for each country. We also generated AMR burden forecasts up to 2050. We generated 95% uncertainty intervals (UIs) for the final estimates by taking the 2·5th and 97·5th percentiles across 500 draws through the multistage computational pipeline, and models were cross-validated for out-of-sample predictive validity. Findings We estimated 380 000 deaths (95% UI 332 000–426 000) associated with bacterial AMR and 92 800 deaths (78 300–111 000) attributable to bacterial AMR in the EMR in 2021. In the past 31 years, there was considerable variation in AMR mortality trends across countries of the region and different age groups. Between 1990 and 2021, associated deaths among children younger than 5 years decreased by 50·0% (38·2–62·0), while those among adults aged 70 and older rose by over 85·7% (95% UI 57·0–115·7). Six pathogens were identified as the primary generators of burden: Streptococcus pneumoniae, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Acinetobacter baumannii , and Pseudomonas aeruginosa . A substantial increase in the AMR burden due to S aureus was observed between 1990 (28 200 deaths [21 600–34 000]) and 2021 (49 500 deaths [43 100–56 200]); consequently, in 2021, methicillin-resistant S aureus was a leading pathogen–drug combination for most countries in the region for deaths and DALYs attributable to, and associated with AMR. Somalia had the highest age-standardised mortality rates in the region: for deaths attributable to and associated with AMR per 100 000 population in both 1990 and 2021; conversely, the country with the lowest burden in the EMR was Qatar. By 2050, the number of deaths attributable to AMR in region is forecasted to reach 187 000 (157 000–223 000) and deaths associated with AMR were projected to reach 752 000 (629 000–879 000). Interpretation Our study shows that bacterial AMR has been a serious public health threat in the EMR for more than 30 years, with a substantial fatal and non-fatal burden for priority bacterial pathogens and pathogen–drug combinations. The magnitude of this issue, future projects, and the inadequate response capacity in many countries underscore the need for more stringent regional leadership in this field. The insights gained from this study can direct targeted mitigation strategies for individual countries within the region, aiding in resource allocation and funding decisions, and emphasising the need for collaborative multisectoral endeavours among nations to address this issue. Funding Wellcome Trust, and the UK Department of Health and Social Care using aid funding managed by the Fleming Fund.

Background: Cardiovascular diseases (CVDs) are the leading cause of mortality and are among the foremost causes of disability globally. CVD burden has continued to increase in most countries since 1990, with trends driven by changing exposures to harmful risk factors, population growth, and population aging. Objectives: We report estimates of global, national, and subnational CVD burden, including 18 subdiseases and 12 associated modifiable risk factors. We analyzed change in CVD burden from 1990 to 2023 and identified drivers of change including population growth, population aging, and risk factor exposure. Methods: The Global Burden of Disease (GBD) 2023 study, a multinational collaborative research study, quantified burden due to 375 diseases including CVD burden and identified drivers of change from 1990 to 2023 using all available data and statistical models. GBD 2023 estimated the population-level burden of diseases in 204 countries and territories from 1990 to 2023. Results: CVDs were the leading cause of disability-adjusted life years (DALYs) and deaths estimated in the GBD. As of 2023, there were 437 million (95% UI: 401 to 465 million) CVD DALYs globally, a 1.4-fold increase from the number in 1990 of 320 million (292 to 344 million). Ischemic heart disease, intracerebral hemorrhage, ischemic stroke, and hypertensive heart disease were the leading cardiovascular causes of DALYs in 2023 globally. As of 2023, age-standardized CVD DALY rates were highest in low and low-middle Socio-demographic Index (SDI) settings and lowest in high SDI settings. The number of CVD deaths increased globally from 13.1 million (95% UI: 12.2 to 14.0 million) in 1990 to 19.2 million (95% UI: 17.4 to 20.4 million) in 2023. The number of prevalent cases of CVD more than doubled since 1990, with 311 million (95% UI: 294 to 333 million) prevalent cases of CVD in 1990 and 626 million (95% UI: 591 to 672 million) prevalent cases in 2023 globally. A total of 79.6% (95% UI: 75.7% to 82.5%) of CVD burden is attributable to modifiable risk factors 347 million [95% UI: 318 to 373 million] DALYs in 2023). Globally, high systolic blood pressure, dietary risks, high low-density lipoprotein cholesterol, and air pollution were the modifiable risks responsible for most attributable CVD burden in 2023. Since 1990, changes in exposure to modifiable risk factors have had mixed effects on CVD burden, with increases in high body mass index, high fasting plasma glucose, and low physical activity leading to higher burden, while reductions in tobacco usage have mitigated some of these increases. Population growth and population aging were the main drivers of the increasing burden since 1990, adding 128 million (95% UI: 115 to 139 million) and 139 million (95% UI: 126 to 151 million) CVD DALYs to the increase in CVD burden since 1990. Conclusions: CVD remains the leading cause of disease burden and death worldwide with the greatest burden in low, low-middle, and middle SDI regions. Large variation exists in CVD burden even for countries at similar levels of development, a gap explained substantially by known, modifiable risk factors that are inadequately controlled. The decades-long increase in CVD burden was the result of population growth, population aging, and increased exposure to a subset of risk factors led by metabolic risks. Countries will need to adopt effective health system and public health strategies if they are to progress in achieving global goals to reduce the burden of CVD.

Background Violence against women and against children are human rights violations with lasting harms to survivors and societies at large. Intimate partner violence (IPV) and sexual violence against children (SVAC) are two major forms of such abuse. Despite their wide-reaching effects on individual and community health, these risk factors have not been adequately prioritised as key drivers of global health burden. Comprehensive x§and reliable estimates of the comparative health burden of IPV and SVAC are urgently needed to inform investments in prevention and support for survivors at both national and global levels. Methods We estimated the prevalence and attributable burden of IPV among females and SVAC among males and females for 204 countries and territories, by age and sex, from 1990 to 2023, as part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2023. We searched several global databases for data on self-reported exposure to IPV and SVAC and undertook a systematic review to identify the health outcomes associated with each of these risk factors. We modelled IPV and SVAC prevalence using spatiotemporal Gaussian process regression, applying data adjustments to account for measurement heterogeneity. We employed burden-of-proof methodology to estimate relative risks for outcomes associated with IPV and SVAC. These estimates informed the calculation of population attributable fractions, which were then used to quantify disability-adjusted life-years (DALYs) attributable to each risk factor. Findings Globally, in 2023, we estimated that 608 million (95% uncertainty interval 518–724) females aged 15 years and older had ever been exposed to IPV, and 1·01 billion (0·764–1·48) individuals aged 15 years and older had experienced sexual violence during childhood. 18·5 million (8·74–30·0) DALYs were attributed to IPV among females and 32·2 million (16·4–52·5) DALYs were attributed to SVAC among males and females in 2023. IPV and SVAC were among the top contributors to the global disease burden in 2023, particularly among females aged 15–49 years, ranking as the fourth and fifth leading risk factors, respectively, for DALYs in this group. Among the eight health outcomes found to be associated with IPV, anxiety disorders and major depressive disorder were the leading causes of IPV-attributed DALYs, accounting for 5·43 million (–1·25 to 14·6) and 3·96 million (1·71 to 6·92) DALYs in 2023, respectively. SVAC was associated with 14 health outcomes, including mental health disorder, substance use disorder, and chronic and infectious disease outcomes. Self-harm and schizophrenia were the leading causes of SVAC-attributed burden, with SVAC accounting for 6·71 million (2·00 to 12·7) DALYs due to self-harm and 4·15 million (–1·92 to 13·1) DALYs due to schizophrenia in 2023. Interpretation IPV and SVAC are substantial contributors to global health burden, and their health consequences span a variety of individual health outcomes. Importantly, mental health disorders account for the greatest share of disease burden among survivors. Investing in prevention of these avoidable risk factors has the potential to avert millions of DALYs and considerable premature mortality each year. Our findings represent strong evidence for global and national leaders to elevate IPV and SVAC among public health priorities. Sustained investments are needed to prevent IPV and SVAC and to implement interventions focused on supporting the complex social and health needs of survivors. Funding Gates Foundation.

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: 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: Enteric infectious diseases claim more than 1 million lives annually and are among the top ten causes of death in children younger than 5 years. Remarkable global investment has been dedicated to enteric infectious disease prevention and control; however, the shifting global health landscape is testing the continuance of progress. To evaluate the current status and guide future interventions, we present the latest epidemiological estimates of enteric infectious diseases from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 and assess progress towards the Global Action Plan for the Prevention and Control of Pneumonia and Diarrhoea (GAPPD) mortality target of fewer than 20 deaths per 100 000 children younger than 5 years by 2025. Methods: We quantified the incidence, mortality, and disability-adjusted life-years (DALYs) of enteric infectious diseases by age, sex, and year across 204 countries and territories from 1990 to 2023. In GBD 2023, the following were considered under the category of enteric infectious diseases: diarrhoeal diseases, enteric fever (typhoid and paratyphoid), invasive non-typhoidal Salmonella spp (iNTS) infections, and other intestinal infectious diseases. We also examined 15 aetiologies contributing to diarrhoeal diseases. Incidence and prevalence were estimated with DisMod-MR (version 2.1), a Bayesian meta-regression tool, drawing on data from systematic reviews, population-based surveys, claims data, and hospital sources. Cause-specific mortality was modelled with Cause of Death Ensemble Modelling based on data from sources including vital registration, mortality surveillance, verbal autopsy, and minimally invasive tissue sampling. Years of life lost and years lived with disability were computed and combined to derive DALYs. For aetiology-specific estimation, population-attributable fractions (PAFs) for 15 pathogens were derived with a counterfactual framework. Point estimates and 95% uncertainty intervals (UIs) were generated from 250 draws from the posterior distribution. Findings: In 2023, enteric infectious diseases resulted in an estimated 1·27 million (95% UI 0·963–1·68) deaths globally, declining from 3·69 million (3·04–4·56) in 1990. The global age-standardised mortality rate (ASMR) decreased from 74·1 (62·0–92·9) per 100 000 population to 16·4 (12·6–21·3) per 100 000 population during the same period. Diarrhoeal diseases accounted for most deaths in 2023 (1·11 million [0·811–1·54]), followed by enteric fever and iNTS. South Asia and sub-Saharan Africa remained the most affected regions in 2023, with 599 000 (441 000–882 000) and 501 000 (373 000–648 000) deaths due to enteric infectious diseases, respectively, predominantly from diarrhoeal disease. Rotavirus was the leading cause of all-age diarrhoeal disease deaths (PAF 16·3% [12·0–21·5]), followed by norovirus (10·2% [2·4–17·0]) and Shigella spp (9·3% [5·4–15·2]). Among children younger than 5 years, PAFs of deaths due to diarrhoeal diseases were 40·2% (32·5–48·5) for rotavirus, 24·0% (15·1–36·7) for Shigella spp, and 23·4% (13·7–34·3) for adenovirus. Across 204 countries and territories, 141 met the GAPPD mortality target in 2023. The driving aetiologies among countries that did not meet the target in 2023 varied slightly by GBD super-region, but the highest or second-highest number of deaths in children younger than 5 years were consistently attributed to rotavirus. Astrovirus and sapovirus, newly included in GBD 2023, were responsible for 24 600 (6290–49 000) and 18 800 (4650–44 400) deaths, respectively, in 2023, mainly in children younger than 5 years. Interpretation: Our findings show that mortality and ASMRs of enteric infectious diseases declined substantially between 1990 and 2023. This decline is consistent with the expansion of public health measures and broader socioeconomic development. However, the burden in 2023 remains considerably high, with the highest mortality concentrated in sub-Saharan Africa and south Asia. Considering that more than a quarter of all countries had yet to meet the GAPPD mortality target in 2023, sustained efforts are needed to address the persistent burden in affected countries and to adapt to the changing global health landscape. Funding: Gates Foundation.

Background: Tuberculosis (TB) is the leading global cause of death from a single infectious agent. Recent reductions in global health funding have threatened TB control, making comprehensive assessment of TB, HIV-related TB, and drug-resistant TB burdens before these disruptions essential for shaping effective responses. The WHO End TB Strategy sets targets of a 95% reduction in TB deaths and a 90% reduction in TB incidence between 2015 and 2035. Using results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, this study aims to assess the burden of TB and multidrug-resistant TB (MDR-TB) across 204 countries and territories, and to evaluate progress towards the WHO End TB incidence and mortality targets. Methods: We quantified TB mortality using the Cause of Death Ensemble modelling platform with global vital registration, surveillance, verbal autopsy, and minimally invasive tissue sampling data. For TB morbidity estimation, we simultaneously modelled incidence, prevalence, and mortality by age and sex using DisMod-MR 2.1. A population attributable fraction (PAF) approach was applied to stratify morbidity and mortality estimates by HIV and drug-resistance status. We also calculated disability-adjusted life-years (DALYs) as the sum of years of life lost and years lived with disability. For the risk factor analysis, a comparative risk assessment framework was used and PAFs were derived for alcohol use, smoking, and high fasting plasma glucose to determine the proportion of TB burden associated with these risk factors. Findings: In 2023, there were an estimated 9·11 million (95% uncertainty interval 8·04–10·3) incident cases of all-form TB, 1·22 million (0·98–1·49) deaths, and 54·6 million (43·8–65·5) DALYs globally. HIV-related TB comprised 781 000 (690 000–879 000) incident cases and 210 000 (142 000–279 000) deaths, contributing 11·0 million (7·56–14·3) DALYs. MDR-TB accounted for 466 000 (198 000–1 080 000) incident cases, 102 000 (31 700–238 000) deaths, and 3·96 million (1·31–9·01) DALYs. From 2015 to 2023, global all-form TB incidence rates declined by 19·2% (17·8–20·5) and deaths declined by 22·6% (4·7–35·7); declines were larger for drug-susceptible TB than for MDR-TB. Sub-Saharan Africa and south Asia had the highest mortality burdens in 2023; reductions in all-form TB incidence and mortality were uneven between 2000 and 2023, with limited progress in both measures in Latin America and the Caribbean. Removing smoking, alcohol use, and high fasting plasma glucose would reduce global TB deaths to 768 000 (592 000–970 000) and DALYs to 34·9 million (27·8–43·8) in 2023; MDR-TB deaths would decrease to 77 200 (23 400–183 000) and DALYs to 3·12 million (1·03–7·29). Interpretation: Global progress towards WHO End TB targets is disparate and fragile. Although many regions achieved meaningful gains, others have stagnated in recent years. The complexity of TB prevention is amplified by divergent MDR-TB trends, the persistent burden of HIV, and growing exposure to modifiable risk factors. Recent volatility in global health financing threatens to further destabilise this vulnerable epidemiological landscape; concerted action is urgently needed to temper disruptions and preserve progress. Funding: Gates Foundation.