Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk–outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk–outcome pairs, and new data on risk exposure levels and risk–outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk–outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46?749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings In 2017, 34·1 million (95% uncertainty interval [UI] 33·3–35·0) deaths and 1·21 billion (1·14–1·28) DALYs were attributable to GBD risk factors. Globally, 61·0% (59·6–62·4) of deaths and 48·3% (46·3–50·2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10·4 million (9·39–11·5) deaths and 218 million (198–237) DALYs, followed by smoking (7·10 million [6·83–7·37] deaths and 182 million [173–193] DALYs), high fasting plasma glucose (6·53 million [5·23–8·23] deaths and 171 million [144–201] DALYs), high body-mass index (BMI; 4·72 million [2·99–6·70] deaths and 148 million [98·6–202] DALYs), and short gestation for birthweight (1·43 million [1·36–1·51] deaths and 139 million [131–147] DALYs). In total, risk-attributable DALYs declined by 4·9% (3·3–6·5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23·5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18·6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health plannin

Global, regional, and national burden of respiratory tract cancers and associated risk factors from 1990 to 2019 a systematic analysis for the Global Burden of Disease Study 2019

BackgroundPrevention, control, and treatment of respiratory tract cancers are important steps towards achieving target 3.4 of the UN Sustainable Development Goals (SDGs)-a one-third reduction in premature mortality due to non-communicable diseases by 2030. We aimed to provide global, regional, and national estimates of the burden of tracheal, bronchus, and lung cancer and larynx cancer and their attributable risks from 1990 to 2019.MethodsBased on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 methodology, we evaluated the incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs) of respiratory tract cancers (ie, tracheal, bronchus, and lung cancer and larynx cancer). Deaths from tracheal, bronchus, and lung cancer and larynx cancer attributable to each risk factor were estimated on the basis of risk exposure, relative risks, and the theoretical minimum risk exposure level input from 204 countries and territories, stratified by sex and Socio-demographic Index (SDI). Trends were estimated from 1990 to 2019, with an emphasis on the 2010-19 period.FindingsGlobally, there were 2·26 million (95% uncertainty interval 2·07 to 2·45) new cases of tracheal, bronchus, and lung cancer, and 2·04 million (1·88 to 2·19) deaths and 45·9 million (42·3 to 49·3) DALYs due to tracheal, bronchus, and lung cancer in 2019. There were 209 000 (194 000 to 225 000) new cases of larynx cancer, and 123 000 (115 000 to 133 000) deaths and 3·26 million (3·03 to 3·51) DALYs due to larynx cancer globally in 2019. From 2010 to 2019, the number of new tracheal, bronchus, and lung cancer cases increased by 23·3% (12·9 to 33·6) globally and the number of larynx cancer cases increased by 24·7% (16·0 to 34·1) globally. Global age-standardised incidence rates of tracheal, bronchus, and lung cancer decreased by 7·4% (-16·8 to 1·6) and age-standardised incidence rates of larynx cancer decreased by 3·0% (-10·5 to 5·0) in males over the past decade; however, during the same period, age-standardised incidence rates in females increased by 0·9% (-8·2 to 10·2) for tracheal, bronchus, and lung cancer and decreased by 0·5% (-8·4 to 8·1) for larynx cancer. Furthermore, although age-standardised incidence and death rates declined in both sexes combined from 2010 to 2019 at the global level for tracheal, bronchus, lung and larynx cancers, some locations had rising rates, particularly those on the lower end of the SDI range. Smoking contributed to an estimated 64·2% (61·9-66·4) of all deaths from tracheal, bronchus, and lung cancer and 63·4% (56·3-69·3) of all deaths from larynx cancer in 2019. For males and for both sexes combined, smoking was the leading specific risk factor for age-standardised deaths from tracheal, bronchus, and lung cancer per 100 000 in all SDI quintiles and GBD regions in 2019. However, among females, household air pollution from solid fuels was the leading specific risk factor in the low SDI quintile and in three GBD regions (central, eastern, and western sub-Saharan Africa) in 2019.InterpretationThe numbers of incident cases and deaths from tracheal, bronchus, and lung cancer and larynx cancer increased globally during the past decade. Even more concerning, age-standardised incidence and death rates due to tracheal, bronchus, lung cancer and larynx cancer increased in some populations-namely, in the lower SDI quintiles and among females. Preventive measures such as smoking control interventions, air quality management programmes focused on major air pollution sources, and widespread access to clean energy should be prioritised in these settings

The global epidemiology and health burden of the autism spectrum: findings from the Global Burden of Disease Study 2021

Background: High-quality estimates of the epidemiology of the autism spectrum and the health needs of autistic people are necessary for service planners and resource allocators. Here we present the global prevalence and health burden of autism spectrum disorder from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 following improvements to the epidemiological data and burden estimation methods. Methods: For GBD 2021, a systematic literature review involving searches in PubMed, Embase, PsycINFO, the Global Health Data Exchange, and consultation with experts identified data on the epidemiology of autism spectrum disorder. Eligible data were used to estimate prevalence via a Bayesian meta-regression tool (DisMod-MR 2.1). Modelled prevalence and disability weights were used to estimate health burden in years lived with disability (YLDs) as the measure of non-fatal health burden and disability-adjusted life-years (DALYs) as the measure of overall health burden. Data by ethnicity were not available. People with lived experience of autism were involved in the design, preparation, interpretation, and writing of this Article. Findings: An estimated 61·8 million (95% uncertainty interval 52·1–72·7) individuals (one in every 127 people) were on the autism spectrum globally in 2021. The global age-standardised prevalence was 788·3 (663·8–927·2) per 100 000 people, equivalent to 1064·7 (898·5–1245·7) autistic males per 100 000 males and 508·1 (424·6–604·3) autistic females per 100 000 females. Autism spectrum disorder accounted for 11·5 million (7·8–16·3) DALYs, equivalent to 147·6 (100·2–208·2) DALYs per 100 000 people (age-standardised) globally. At the super-region level, age-standardised DALY rates ranged from 126·5 (86·0–178·0) per 100 000 people in southeast Asia, east Asia, and Oceania to 204·1 (140·7–284·7) per 100 000 people in the high-income super-region. DALYs were evident across the lifespan, emerging for children younger than age 5 years (169·2 [115·0–237·4] DALYs per 100 000 people) and decreasing with age (163·4 [110·6–229·8] DALYs per 100 000 people younger than 20 years and 137·7 [93·9–194·5] DALYs per 100 000 people aged 20 years and older). Autism spectrum disorder was ranked within the top-ten causes of non-fatal health burden for people younger than 20 years. Interpretation: The high prevalence and high rank for non-fatal health burden of autism spectrum disorder in people younger than 20 years underscore the importance of early detection and support to autistic young people and their caregivers globally. Work to improve the precision and global representation of our findings is required, starting with better global coverage of epidemiological data so that geographical variations can be better ascertained. The work presented here can guide future research efforts, and importantly, decisions concerning allocation of health services that better address the needs of all autistic individuals. Funding: Queensland Health and the Bill & Melinda Gates Foundation.</p

Assessing performance of the Healthcare Access and Quality Index, overall and by select age groups, for 204 countries and territories, 1990–2019: a systematic analysis from the Global Burden of Disease Study 2019

Assessing performance of the Healthcare Access and Quality Index, overall and by select age groups, for 204 countries and territories, 1990–2019: a systematic analysis from the Global Burden of Disease Study 201

Assessing performance of the Healthcare Access and Quality Index, overall and by select age groups, for 204 countries and territories, 1990-2019: a systematic analysis from the Global Burden of Disease Study 2019

BACKGROUND: Health-care needs change throughout the life course. It is thus crucial to assess whether health systems provide access to quality health care for all ages. Drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019), we measured the Healthcare Access and Quality (HAQ) Index overall and for select age groups in 204 locations from 1990 to 2019. METHODS: We distinguished the overall HAQ Index (ages 0-74 years) from scores for select age groups: the young (ages 0-14 years), working (ages 15-64 years), and post-working (ages 65-74 years) groups. For GBD 2019, HAQ Index construction methods were updated to use the arithmetic mean of scaled mortality-to-incidence ratios (MIRs) and risk-standardised death rates (RSDRs) for 32 causes of death that should not occur in the presence of timely, quality health care. Across locations and years, MIRs and RSDRs were scaled from 0 (worst) to 100 (best) separately, putting the HAQ Index on a different relative scale for each age group. We estimated absolute convergence for each group on the basis of whether the HAQ Index grew faster in absolute terms between 1990 and 2019 in countries with lower 1990 HAQ Index scores than countries with higher 1990 HAQ Index scores and by Socio-demographic Index (SDI) quintile. SDI is a summary metric of overall development. FINDINGS: Between 1990 and 2019, the HAQ Index increased overall (by 19·6 points, 95% uncertainty interval 17·9-21·3), as well as among the young (22·5, 19·9-24·7), working (17·2, 15·2-19·1), and post-working (15·1, 13·2-17·0) age groups. Large differences in HAQ Index scores were present across SDI levels in 2019, with the overall index ranging from 30·7 (28·6-33·0) on average in low-SDI countries to 83·4 (82·4-84·3) on average in high-SDI countries. Similarly large ranges between low-SDI and high-SDI countries, respectively, were estimated in the HAQ Index for the young (40·4-89·0), working (33·8-82·8), and post-working (30·4-79·1) groups. Absolute convergence in HAQ Index was estimated in the young group only. In contrast, divergence was estimated among the working and post-working groups, driven by slow progress in low-SDI countries. INTERPRETATION: Although major gaps remain across levels of social and economic development, convergence in the young group is an encouraging sign of reduced disparities in health-care access and quality. However, divergence in the working and post-working groups indicates that health-care access and quality is lagging at lower levels of social and economic development. To meet the needs of ageing populations, health systems need to improve health-care access and quality for working-age adults and older populations while continuing to realise gains among the young. FUNDING: Bill & Melinda Gates Foundation

Tracking development assistance for health and for COVID-19: a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050

BackgroundThe rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020.MethodsWe estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050.FindingsIn 2019, health spending globally reached$8·8 trillion (95% uncertainty interval [UI] 8·7–8·8) or $1132 (1119–1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total,$40·4 billion (0·5%, 95% UI 0·5–0·5) was development assistance for health provided to low-income and middle-income countries, which made up 24·6% (UI 24·0–25·1) of total spending in low-income countries. We estimate that $54·8 billion in development assistance for health was disbursed in 2020. Of this,$13·7 billion was targeted toward the COVID-19 health response. $12·3 billion was newly committed and$1·4 billion was repurposed from existing health projects. $3·1 billion (22·4$2·4 billion (17·9%) was for supply chain and logistics. Only $714·4 million (7·7$1519 (1448–1591) per person in 2050, although spending across countries is expected to remain varied.InterpretationGlobal health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all.</h4

Global, regional, and national burden of suicide, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Deaths from suicide are a tragic yet preventable cause of mortality. Quantifying the burden of suicide to understand its geographical distribution, temporal trends, and variation by age and sex is an essential step in suicide prevention. We aimed to present a comprehensive set of global, regional, and national estimates of suicide burden. Methods: We produced estimates of the number of deaths and age-standardised mortality rates of suicide globally, regionally, and for 204 countries and territories from 1990 to 2021, and disaggregated these results by age and sex. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 estimates of deaths attributable to suicide were broken down into two comprehensive categories: those by firearms and those by other specified means. For this analysis, we also produced estimates of mean age at the time of death from suicide, incidence of suicide attempts compared with deaths, and age-standardised rates of suicide by firearm. We acquired data from vital registration, verbal autopsy, and mortality surveillance that included 23 782 study-location-years of data from GBD 2021. Point estimates were calculated from the average of 1000 randomly selected possible values of deaths from suicide by age, sex, and geographical location. 95% uncertainty intervals (UIs) were derived from the 2·5th and 97·5th percentiles from a 1000-draw distribution. Findings: Globally, 746 000 deaths (95% UI 692 000–800 000) from suicide occurred in 2021, including 519 000 deaths (485 000–556 000) among males and 227 000 (200 000–255 000) among females. The age-standardised mortality rate has declined over time, from 14·9 deaths (12·8–15·7) per 100 000 population in 1990 to 9·0 (8·3–9·6) per 100 000 in 2021. Regionally, mortality rates due to suicide were highest in eastern Europe (19·2 [17·5–20·8] per 100 000), southern sub-Saharan Africa (16·1 [14·0–18·3] per 100 000), and central sub-Saharan Africa (14·4 [11·0–19·1] per 100 000). The mean age at which individuals died from suicide progressively increased during the study period. For males, the mean age at death by suicide in 1990 was 43·0 years (38·0–45·8), increasing to 47·0 years (43·5–50·6) in 2021. For females, it was 41·9 years (30·9–46·7) in 1990 and 46·9 years (41·2–52·8) in 2021. The incidence of suicide attempts requiring medical care was consistently higher at the regional level for females than for males. The number of deaths by suicide using firearms was higher for males than for females, and substantially varied by country and region. The countries with the highest age-standardised rate of suicides attributable to firearms in 2021 were the USA, Uruguay, and Venezuela. Interpretation: Deaths from suicide remain variable by age and sex and across geographical locations, although population mortality rates have continued to improve globally since the 1990s. This study presents, for the first time in GBD, a quantification of the mean age at the time of suicide death, alongside comprehensive estimates of the burden of suicide throughout the world. These analyses will help guide future approaches to reduce suicide mortality that consider a public health framework for prevention. Funding: Bill & Melinda Gates Foundation.</p

Global, regional, and national disability-adjusted life-years (DALYs) for 359 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017

Global, regional, and national disability-adjusted life-years (DALYs) for 359 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 201

Global, regional, and national mortality among young people aged 10-24 years, 1950-2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: Documentation of patterns and long-term trends in mortality in young people, which reflect huge changes in demographic and social determinants of adolescent health, enables identification of global investment priorities for this age group. We aimed to analyse data on the number of deaths, years of life lost, and mortality rates by sex and age group in people aged 10–24 years in 204 countries and territories from 1950 to 2019 by use of estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Methods: We report trends in estimated total numbers of deaths and mortality rate per 100 000 population in young people aged 10–24 years by age group (10–14 years, 15–19 years, and 20–24 years) and sex in 204 countries and territories between 1950 and 2019 for all causes, and between 1980 and 2019 by cause of death. We analyse variation in outcomes by region, age group, and sex, and compare annual rate of change in mortality in young people aged 10–24 years with that in children aged 0–9 years from 1990 to 2019. We then analyse the association between mortality in people aged 10–24 years and socioeconomic development using the GBD Socio-demographic Index (SDI), a composite measure based on average national educational attainment in people older than 15 years, total fertility rate in people younger than 25 years, and income per capita. We assess the association between SDI and all-cause mortality in 2019, and analyse the ratio of observed to expected mortality by SDI using the most recent available data release (2017). Findings: In 2019 there were 1·49 million deaths (95% uncertainty interval 1·39–1·59) worldwide in people aged 10–24 years, of which 61% occurred in males. 32·7% of all adolescent deaths were due to transport injuries, unintentional injuries, or interpersonal violence and conflict; 32·1% were due to communicable, nutritional, or maternal causes; 27·0% were due to non-communicable diseases; and 8·2% were due to self-harm. Since 1950, deaths in this age group decreased by 30·0% in females and 15·3% in males, and sex-based differences in mortality rate have widened in most regions of the world. Geographical variation has also increased, particularly in people aged 10–14 years. Since 1980, communicable and maternal causes of death have decreased sharply as a proportion of total deaths in most GBD super-regions, but remain some of the most common causes in sub-Saharan Africa and south Asia, where more than half of all adolescent deaths occur. Annual percentage decrease in all-cause mortality rate since 1990 in adolescents aged 15–19 years was 1·3% in males and 1·6% in females, almost half that of males aged 1–4 years (2·4%), and around a third less than in females aged 1–4 years (2·5%). The proportion of global deaths in people aged 0–24 years that occurred in people aged 10–24 years more than doubled between 1950 and 2019, from 9·5% to 21·6%. Interpretation: Variation in adolescent mortality between countries and by sex is widening, driven by poor progress in reducing deaths in males and older adolescents. Improving global adolescent mortality will require action to address the specific vulnerabilities of this age group, which are being overlooked. Furthermore, indirect effects of the COVID-19 pandemic are likely to jeopardise efforts to improve health outcomes including mortality in young people aged 10–24 years. There is an urgent need to respond to the changing global burden of adolescent mortality, address inequities where they occur, and improve the availability and quality of primary mortality data in this age group. Funding: Bill & Melinda Gates Foundation

Global, regional, and national burden of epilepsy, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Epilepsy is one of the most common serious neurological disorders and affects individuals of all ages across the globe. The aim of this study is to provide estimates of the epilepsy burden on the global, regional, and national levels for 1990–2021. Methods: Using well established Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) methodology, we quantified the prevalence of active idiopathic (epilepsy of genetic or unknown origin) and secondary epilepsy (epilepsy due to an underlying abnormality of the brain structure or chemistry), as well as incidence, death, and disability-adjusted life-years (DALYs) by age, sex, and location (globally, 21 GBD regions and seven super-regions, World Bank country income levels, Socio-demographic Index [SDI], and 204 countries) and their trends from 1990 to 2021. Vital registrations and verbal autopsies provided information about deaths, and data on the prevalence and severity of epilepsy, largely came from population representative surveys. All estimates were calculated with 95% uncertainty intervals (UIs). Findings: In 2021, there were 51·7 million (95% UI 44·9–58·9) people with epilepsy (idiopathic and secondary combined) globally, with an age-standardised prevalence of 658 per 100 000 (569–748). Idiopathic epilepsy had an age-standardised prevalence of 307 per 100 000 (235–389) globally, with 24·2 million (18·5–30·7) prevalent cases, and secondary epilepsy had a global age-standardised prevalence of 350 per 100 000 (322–380). In 2021, 0·7% of the population had active epilepsy (0·3% attributed to idiopathic epilepsy and 0·4% to secondary epilepsy), and the age-standardised global prevalence of epilepsy from idiopathic and secondary epilepsy combined increased from 1990 to 2021 by 10·8% (1·1–21·3), mainly due to corresponding changes in secondary epilepsy. However, age-standardised death and DALY rates of idiopathic epilepsy reduced from 1990 to 2021 (decline of 15·8% [8·8–22·8] and 14·5% [4·2–24·2], respectively). There were three-fold to four-fold geographical differences in the burden of active idiopathic epilepsy, with the bulk of the burden residing in low-income to middle-income countries: 82·1% (81·1–83·4) of incident, 80·4% prevalent (79·7–82·7), 84·7% (83·7–85·1) fatal epilepsy, and 87·9% (86·2–89·2) epilepsy DALYs. Interpretation: Although the global trends in idiopathic epilepsy deaths and DALY rates have improved in the preceding decades, in 2021 there were almost 52 million people with active epilepsy (24 million from idiopathic epilepsy and 28 million from secondary epilepsy), with the bulk of the burden (>80%) residing in low-income to middle-income countries. Better treatment and prevention of epilepsy are required, along with further research on risk factors of idiopathic epilepsy, good-quality long-term epilepsy surveillance studies, and exploration of the possible effect of stigma and cultural differences in seeking medical attention for epilepsy. Funding: Bill and Melinda Gates Foundatio