Measuring and forecasting progress towards the education-related SDG targets.

Education is a key dimension of well-being and a crucial indicator of development1-4. The Sustainable Development Goals (SDGs) prioritize progress in education, with a new focus on inequality5-7. Here we model the within-country distribution of years of schooling, and use this model to explore educational inequality since 1970 and to forecast progress towards the education-related 2030 SDG targets. We show that although the world is largely on track to achieve near-universal primary education by 2030, substantial challenges remain in the completion rates for secondary and tertiary education. Globally, the gender gap in schooling had nearly closed by 2018 but gender disparities remained acute in parts of sub-Saharan Africa, and North Africa and the Middle East. It is predicted that, by 2030, females will have achieved significantly higher educational attainment than males in 18 countries. Inequality in education reached a peak globally in 2017 and is projected to decrease steadily up to 2030. The distributions and inequality metrics presented here represent a framework that can be used to track the progress of each country towards the SDG targets and the level of inequality over time. Reducing educational inequality is one way to promote a fairer distribution of human capital and the development of more equitable human societies.

Mapping HIV prevalence in sub-Saharan Africa between 2000 and 2017.

HIV/AIDS is a leading cause of disease burden in sub-Saharan Africa. Existing evidence has demonstrated that there is substantial local variation in the prevalence of HIV; however, subnational variation has not been investigated at a high spatial resolution across the continent. Here we explore within-country variation at a 5 × 5-km resolution in sub-Saharan Africa by estimating the prevalence of HIV among adults (aged 15-49 years) and the corresponding number of people living with HIV from 2000 to 2017. Our analysis reveals substantial within-country variation in the prevalence of HIV throughout sub-Saharan Africa and local differences in both the direction and rate of change in HIV prevalence between 2000 and 2017, highlighting the degree to which important local differences are masked when examining trends at the country level. These fine-scale estimates of HIV prevalence across space and time provide an important tool for precisely targeting the interventions that are necessary to bringing HIV infections under control in sub-Saharan Africa.

Assessing COVID-19 pandemic policies and behaviours and their economic and educational trade-offs across US states from Jan 1, 2020, to July 31, 2022: an observational analysis.

BACKGROUND: The USA struggled in responding to the COVID-19 pandemic, but not all states struggled equally. Identifying the factors associated with cross-state variation in infection and mortality rates could help to improve responses to this and future pandemics. We sought to answer five key policy-relevant questions regarding the following: 1) what roles social, economic, and racial inequities had in interstate variation in COVID-19 outcomes; 2) whether states with greater health-care and public health capacity had better outcomes; 3) how politics influenced the results; 4) whether states that imposed more policy mandates and sustained them longer had better outcomes; and 5) whether there were trade-offs between a state having fewer cumulative SARS-CoV-2 infections and total COVID-19 deaths and its economic and educational outcomes. METHODS: Data disaggregated by US state were extracted from public databases, including COVID-19 infection and mortality estimates from the Institute for Health Metrics and Evaluation's (IHME) COVID-19 database; Bureau of Economic Analysis data on state gross domestic product (GDP); Federal Reserve economic data on employment rates; National Center for Education Statistics data on student standardised test scores; and US Census Bureau data on race and ethnicity by state. We standardised infection rates for population density and death rates for age and the prevalence of major comorbidities to facilitate comparison of states' successes in mitigating the effects of COVID-19. We regressed these health outcomes on prepandemic state characteristics (such as educational attainment and health spending per capita), policies adopted by states during the pandemic (such as mask mandates and business closures), and population-level behavioural responses (such as vaccine coverage and mobility). We explored potential mechanisms connecting state-level factors to individual-level behaviours using linear regression. We quantified reductions in state GDP, employment, and student test scores during the pandemic to identify policy and behavioural responses associated with these outcomes and to assess trade-offs between these outcomes and COVID-19 outcomes. Significance was defined as p<0·05. FINDINGS: Standardised cumulative COVID-19 death rates for the period from Jan 1, 2020, to July 31, 2022 varied across the USA (national rate 372 deaths per 100 000 population [95% uncertainty interval [UI] 364-379]), with the lowest standardised rates in Hawaii (147 deaths per 100 000 [127-196]) and New Hampshire (215 per 100 000 [183-271]) and the highest in Arizona (581 per 100 000 [509-672]) and Washington, DC (526 per 100 000 [425-631]). A lower poverty rate, higher mean number of years of education, and a greater proportion of people expressing interpersonal trust were statistically associated with lower infection and death rates, and states where larger percentages of the population identify as Black (non-Hispanic) or Hispanic were associated with higher cumulative death rates. Access to quality health care (measured by the IHME's Healthcare Access and Quality Index) was associated with fewer total COVID-19 deaths and SARS-CoV-2 infections, but higher public health spending and more public health personnel per capita were not, at the state level. The political affiliation of the state governor was not associated with lower SARS-CoV-2 infection or COVID-19 death rates, but worse COVID-19 outcomes were associated with the proportion of a state's voters who voted for the 2020 Republican presidential candidate. State governments' uses of protective mandates were associated with lower infection rates, as were mask use, lower mobility, and higher vaccination rate, while vaccination rates were associated with lower death rates. State GDP and student reading test scores were not associated with state COVD-19 policy responses, infection rates, or death rates. Employment, however, had a statistically significant relationship with restaurant closures and greater infections and deaths: on average, 1574 (95% UI 884-7107) additional infections per 10 000 population were associated in states with a one percentage point increase in employment rate. Several policy mandates and protective behaviours were associated with lower fourth-grade mathematics test scores, but our study results did not find a link to state-level estimates of school closures. INTERPRETATION: COVID-19 magnified the polarisation and persistent social, economic, and racial inequities that already existed across US society, but the next pandemic threat need not do the same. US states that mitigated those structural inequalities, deployed science-based interventions such as vaccination and targeted vaccine mandates, and promoted their adoption across society were able to match the best-performing nations in minimising COVID-19 death rates. These findings could contribute to the design and targeting of clinical and policy interventions to facilitate better health outcomes in future crises. FUNDING: Bill & Melinda Gates Foundation, J Stanton, T Gillespie, J and E Nordstrom, and Bloomberg Philanthropies.

Spatial dynamics of malaria transmission.

The Ross-Macdonald model has exerted enormous influence over the study of malaria transmission dynamics and control, but it lacked features to describe parasite dispersal, travel, and other important aspects of heterogeneous transmission. Here, we present a patch-based differential equation modeling framework that extends the Ross-Macdonald model with sufficient skill and complexity to support planning, monitoring and evaluation for Plasmodium falciparum malaria control. We designed a generic interface for building structured, spatial models of malaria transmission based on a new algorithm for mosquito blood feeding. We developed new algorithms to simulate adult mosquito demography, dispersal, and egg laying in response to resource availability. The core dynamical components describing mosquito ecology and malaria transmission were decomposed, redesigned and reassembled into a modular framework. Structural elements in the framework-human population strata, patches, and aquatic habitats-interact through a flexible design that facilitates construction of ensembles of models with scalable complexity to support robust analytics for malaria policy and adaptive malaria control. We propose updated definitions for the human biting rate and entomological inoculation rates. We present new formulas to describe parasite dispersal and spatial dynamics under steady state conditions, including the human biting rates, parasite dispersal, the "vectorial capacity matrix," a human transmitting capacity distribution matrix, and threshold conditions. An [Formula: see text] package that implements the framework, solves the differential equations, and computes spatial metrics for models developed in this framework has been developed. Development of the model and metrics have focused on malaria, but since the framework is modular, the same ideas and software can be applied to other mosquito-borne pathogen systems.

Mapping local variation in educational attainment across Africa.

Educational attainment for women of reproductive age is linked to reduced child and maternal mortality, lower fertility and improved reproductive health. Comparable analyses of attainment exist only at the national level, potentially obscuring patterns in subnational inequality. Evidence suggests that wide disparities between urban and rural populations exist, raising questions about where the majority of progress towards the education targets of the Sustainable Development Goals is occurring in African countries. Here we explore within-country inequalities by predicting years of schooling across five by five kilometre grids, generating estimates of average educational attainment by age and sex at subnational levels. Despite marked progress in attainment from 2000 to 2015 across Africa, substantial differences persist between locations and sexes. These differences have widened in many countries, particularly across the Sahel. These high-resolution, comparable estimates improve the ability of decision-makers to plan the precisely targeted interventions that will be necessary to deliver progress during the era of the Sustainable Development Goals.

Mapping child growth failure in Africa between 2000 and 2015.

Insufficient growth during childhood is associated with poor health outcomes and an increased risk of death. Between 2000 and 2015, nearly all African countries demonstrated improvements for children under 5 years old for stunting, wasting, and underweight, the core components of child growth failure. Here we show that striking subnational heterogeneity in levels and trends of child growth remains. If current rates of progress are sustained, many areas of Africa will meet the World Health Organization Global Targets 2025 to improve maternal, infant and young child nutrition, but high levels of growth failure will persist across the Sahel. At these rates, much, if not all of the continent will fail to meet the Sustainable Development Goal target-to end malnutrition by 2030. Geospatial estimates of child growth failure provide a baseline for measuring progress as well as a precision public health platform to target interventions to those populations with the greatest need, in order to reduce health disparities and accelerate progress.

Hearing Loss Prevalence, Years Lived With Disability, and Hearing Aid Use in the United States From 1990 to 2019: Findings From the Global Burden of Disease Study.

OBJECTIVES: This article describes key data sources and methods used to estimate hearing loss in the United States, in the Global Burden of Disease study. Then, trends in hearing loss are described for 2019, including temporal trends from 1990 to 2019, changing prevalence over age, severity patterns, and utilization of hearing aids. DESIGN: We utilized population-representative surveys from the United States to estimate hearing loss prevalence for the Global Burden of Disease study. A key input data source in modeled estimates are the National Health and Nutrition Examination Surveys (NHANES), years 1988 to 2010. We ran hierarchical severity-specific models to estimate hearing loss prevalence. We then scaled severity-specific models to sum to total hearing impairment prevalence, adjusted estimates for hearing aid coverage, and split estimates by etiology and tinnitus status. We computed years lived with disability (YLDs), which quantifies the amount of health loss associated with a condition depending on severity and creates a common metric to compare the burden of disparate diseases. This was done by multiplying the prevalence of severity-specific hearing loss by corresponding disability weights, with additional weighting for tinnitus comorbidity. RESULTS: An estimated 72.88 million (95% uncertainty interval (UI) 68.53 to 77.30) people in the United States had hearing loss in 2019, accounting for 22.2% (20.9 to 23.6) of the total population. Hearing loss was responsible for 2.24 million (1.56 to 3.11) YLDs (3.6% (2.8 to 4.7) of total US YLDs). Age-standardized prevalence was higher in males (17.7% [16.7 to 18.8]) compared with females (11.9%, [11.2 to 12.5]). While most cases of hearing loss were mild (64.3%, 95% UI 61.0 to 67.6), disability was concentrated in cases that were moderate or more severe. The all-age prevalence of hearing loss in the United States was 28.1% (25.7 to 30.8) higher in 2019 than in 1990, despite stable age-standardized prevalence. An estimated 9.7% (8.6 to 11.0) of individuals with mild to profound hearing loss utilized a hearing aid, while 32.5% (31.9 to 33.2) of individuals with hearing loss experienced tinnitus. Occupational noise exposure was responsible for 11.2% (10.2 to 12.4) of hearing loss YLDs. CONCLUSIONS: Results indicate large burden of hearing loss in the United States, with an estimated 1 in 5 people experiencing this condition. While many cases of hearing loss in the United States were mild, growing prevalence, low usage of hearing aids, and aging populations indicate the rising impact of this condition in future years and the increasing importance of domestic access to hearing healthcare services. Large-scale audiometric surveys such as NHANES are needed to regularly assess hearing loss burden and access to healthcare, improving our understanding of who is impacted by hearing loss and what groups are most amenable to intervention.

Measuring contraceptive method mix, prevalence, and demand satisfied by age and marital status in 204 countries and territories, 1970-2019: a systematic analysis for the Global Burden of Disease Study 2019.

BACKGROUND: Meeting the contraceptive needs of women of reproductive age is beneficial for the health of women and children, and the economic and social empowerment of women. Higher rates of contraceptive coverage have been linked to the availability of a more diverse range of contraceptive methods. We present estimates of the contraceptive prevalence rate (CPR), modern contraceptive prevalence rate (mCPR), demand satisfied, and the method of contraception used for both partnered and unpartnered women for 5-year age groups in 204 countries and territories between 1970 and 2019. METHODS: We used 1162 population-based surveys capturing contraceptive use among women between 1970 and 2019, in which women of reproductive age (15-49 years) self-reported their, or their partner's, current use of contraception for family planning purposes. Spatiotemporal Gaussian process regression was used to generate estimates of the CPR, mCPR, demand satisfied, and method mix by age and marital status. We assessed how age-specific mCPR and demand satisfied changed with the Socio-demographic Index (SDI), a measure of social and economic development, using the meta-regression Bayesian, regularised, trimmed method from the Global Burden of Diseases, Injuries, and Risk Factors Study. FINDINGS: In 2019, 162·9 million (95% uncertainty interval [UI] 155·6-170·2) women had unmet need for contraception, of whom 29·3% (27·9-30·6) resided in sub-Saharan Africa and 27·2% (24·4-30·3) resided in south Asia. Women aged 15-19 years (64·8% [62·9-66·7]) and 20-24 years (71·9% [68·9-74·2]) had the lowest rates of demand satisfied, with 43·2 million (95% UI 39·3-48·0) women aged 15-24 years with unmet need in 2019. The mCPR and demand satisfied among women aged 15-19 years were substantially lower than among women aged 20-49 years at SDI values below 60 (on a 0-100 scale), but began to equalise as SDI increased above 60. Between 1970 and 2019, the global mCPR increased by 20·1 percentage points (95% UI 18·7-21·6). During this time, traditional methods declined as a proportion of all contraceptive methods, whereas the use of implants, injections, female sterilisation, and condoms increased. Method mix differs substantially depending on age and geography, with the share of female sterilisation increasing with age and comprising more than 50% of methods in use in south Asia. In 28 countries, one method was used by more than 50% of users in 2019. INTERPRETATION: The dominance of one contraceptive method in some locations raises the question of whether family planning policies should aim to expand method mix or invest in making existing methods more accessible. Lower rates of demand satisfied among women aged 15-24 years are also concerning because unintended pregnancies before age 25 years can forestall or eliminate education and employment opportunities that lead to social and economic empowerment. Policy makers should strive to tailor family planning programmes to the preferences of the groups with the most need, while maintaining the programmes used by existing users. FUNDING: Bill & Melinda Gates Foundation.

Quantifying the effects of the COVID-19 pandemic on gender equality on health, social, and economic indicators: a comprehensive review of data from March, 2020, to September, 2021.

BACKGROUND: Gender is emerging as a significant factor in the social, economic, and health effects of COVID-19. However, most existing studies have focused on its direct impact on health. Here, we aimed to explore the indirect effects of COVID-19 on gender disparities globally. METHODS: We reviewed publicly available datasets with information on indicators related to vaccine hesitancy and uptake, health care services, economic and work-related concerns, education, and safety at home and in the community. We used mixed effects regression, Gaussian process regression, and bootstrapping to synthesise all data sources. We accounted for uncertainty in the underlying data and modelling process. We then used mixed effects logistic regression to explore gender gaps globally and by region. FINDINGS: Between March, 2020, and September, 2021, women were more likely to report employment loss (26·0% [95% uncertainty interval 23·8-28·8, by September, 2021) than men (20·4% [18·2-22·9], by September, 2021), as well as forgoing work to care for others (ratio of women to men: 1·8 by March, 2020, and 2·4 by September, 2021). Women and girls were 1·21 times (1·20-1·21) more likely than men and boys to report dropping out of school for reasons other than school closures. Women were also 1·23 (1·22-1·23) times more likely than men to report that gender-based violence had increased during the pandemic. By September 2021, women and men did not differ significantly in vaccine hesitancy or uptake. INTERPRETATION: The most significant gender gaps identified in our study show intensified levels of pre-existing widespread inequalities between women and men during the COVID-19 pandemic. Political and social leaders should prioritise policies that enable and encourage women to participate in the labour force and continue their education, thereby equipping and enabling them with greater ability to overcome the barriers they face. FUNDING: The Bill & Melinda Gates Foundation.

Disease-specific health spending by age, sex, and type of care in Norway: a national health registry study.

BACKGROUND: Norway is a high-income nation with universal tax-financed health care and among the highest per person health spending in the world. This study estimates Norwegian health expenditures by health condition, age, and sex, and compares it with disability-adjusted life-years (DALYs). METHODS: Government budgets, reimbursement databases, patient registries, and prescription databases were combined to estimate spending for 144 health conditions, 38 age and sex groups, and eight types of care (GPs; physiotherapists & chiropractors; specialized outpatient; day patient; inpatient; prescription drugs; home-based care; and nursing homes) totaling 174,157,766 encounters. Diagnoses were in accordance with the Global Burden of Disease study (GBD). The spending estimates were adjusted, by redistributing excess spending associated with each comorbidity. Disease-specific DALYs were gathered from GBD 2019. RESULTS: The top five aggregate causes of Norwegian health spending in 2019 were mental and substance use disorders (20.7%), neurological disorders (15.4%), cardiovascular diseases (10.1%), diabetes, kidney, and urinary diseases (9.0%), and neoplasms (7.2%). Spending increased sharply with age. Among 144 health conditions, dementias had the highest health spending, with 10.2% of total spending, and 78% of this spending was incurred at nursing homes. The second largest was falls estimated at 4.6% of total spending. Spending in those aged 15-49 was dominated by mental and substance use disorders, with 46.0% of total spending. Accounting for longevity, spending per female was greater than spending per male, particularly for musculoskeletal disorders, dementias, and falls. Spending correlated well with DALYs (Correlation r = 0.77, 95% CI 0.67-0.87), and the correlation of spending with non-fatal disease burden (r = 0.83, 0.76-0.90) was more pronounced than with mortality (r = 0.58, 0.43-0.72). CONCLUSIONS: Health spending was high for long-term disabilities in older age groups. Research and development into more effective interventions for the disabling high-cost diseases is urgently needed.

Clonorchis sinensis Reinfection Rate and Reinfection Determinants: A Prospective Cohort Study in Hengxian County, Guangxi, China.

BACKGROUND: To understand Clonorchis sinensis reinfection and the determinants of reinfection in endemic areas is important in establishment of control measures. METHODS: A prospective cohort study was implemented in Hengxian County, Guangxi, China. Individuals with C. sinensis infection were completely treated, and those cured were enrolled as study subjects and followed up for 3, 6, and 12 months. The reinfection frequency and incidence were calculated, and a multivariable Cox proportional hazard model was constructed to capture reinfection determinants. RESULTS: Among 635 enrolled subjects, 436 (68.7%) completed follow-up. Of these, 177 (40.6%) were reinfected; 133 (75.1%) were reinfected once, 41 (23.2%) twice, and 3 (1.7%) three times. The incidence of reinfection was 64.0 per 100 person-years. Men (adjusted hazard ratio [aHR], 1.67; 95% confidence interval [CI], 1.14-2.44), those with underlying diseases (aHR, 1.41; 95% CI, 1.02-1.95), and those with moderate- or heavy-intensity infections (aHR, 1.45; 95% CI, 1.14-1.85) had increasing reinfection probabilities. CONCLUSIONS: C. sinensis reinfection is high in endemic areas. Men and high-intensity infection are important determinants of reinfection. Repeated chemotherapy is necessary to control reinfection and its associated morbidities, especially in high-risk individuals. In addition, behavioral education is advised to decrease overall reinfection in endemic areas.

Estimating global and regional disruptions to routine childhood vaccine coverage during the COVID-19 pandemic in 2020: a modelling study.

BACKGROUND: The COVID-19 pandemic and efforts to reduce SARS-CoV-2 transmission substantially affected health services worldwide. To better understand the impact of the pandemic on childhood routine immunisation, we estimated disruptions in vaccine coverage associated with the pandemic in 2020, globally and by Global Burden of Disease (GBD) super-region. METHODS: For this analysis we used a two-step hierarchical random spline modelling approach to estimate global and regional disruptions to routine immunisation using administrative data and reports from electronic immunisation systems, with mobility data as a model input. Paired with estimates of vaccine coverage expected in the absence of COVID-19, which were derived from vaccine coverage models from GBD 2020, Release 1 (GBD 2020 R1), we estimated the number of children who missed routinely delivered doses of the third-dose diphtheria-tetanus-pertussis (DTP3) vaccine and first-dose measles-containing vaccine (MCV1) in 2020. FINDINGS: Globally, in 2020, estimated vaccine coverage was 76·7% (95% uncertainty interval 74·3-78·6) for DTP3 and 78·9% (74·8-81·9) for MCV1, representing relative reductions of 7·7% (6·0-10·1) for DTP3 and 7·9% (5·2-11·7) for MCV1, compared to expected doses delivered in the absence of the COVID-19 pandemic. From January to December, 2020, we estimated that 30·0 million (27·6-33·1) children missed doses of DTP3 and 27·2 million (23·4-32·5) children missed MCV1 doses. Compared to expected gaps in coverage for eligible children in 2020, these estimates represented an additional 8·5 million (6·5-11·6) children not routinely vaccinated with DTP3 and an additional 8·9 million (5·7-13·7) children not routinely vaccinated with MCV1 attributable to the COVID-19 pandemic. Globally, monthly disruptions were highest in April, 2020, across all GBD super-regions, with 4·6 million (4·0-5·4) children missing doses of DTP3 and 4·4 million (3·7-5·2) children missing doses of MCV1. Every GBD super-region saw reductions in vaccine coverage in March and April, with the most severe annual impacts in north Africa and the Middle East, south Asia, and Latin America and the Caribbean. We estimated the lowest annual reductions in vaccine delivery in sub-Saharan Africa, where disruptions remained minimal throughout the year. For some super-regions, including southeast Asia, east Asia, and Oceania for both DTP3 and MCV1, the high-income super-region for DTP3, and south Asia for MCV1, estimates suggest that monthly doses were delivered at or above expected levels during the second half of 2020. INTERPRETATION: Routine immunisation services faced stark challenges in 2020, with the COVID-19 pandemic causing the most widespread and largest global disruption in recent history. Although the latest coverage trajectories point towards recovery in some regions, a combination of lagging catch-up immunisation services, continued SARS-CoV-2 transmission, and persistent gaps in vaccine coverage before the pandemic still left millions of children under-vaccinated or unvaccinated against preventable diseases at the end of 2020, and these gaps are likely to extend throughout 2021. Strengthening routine immunisation data systems and efforts to target resources and outreach will be essential to minimise the risk of vaccine-preventable disease outbreaks, reach children who missed routine vaccine doses during the pandemic, and accelerate progress towards higher and more equitable vaccination coverage over the next decade. FUNDING: Bill & Melinda Gates Foundation.

Estimating the cause-specific relative risks of non-optimal temperature on daily mortality: a two-part modelling approach applied to the Global Burden of Disease Study.

BACKGROUND: Associations between high and low temperatures and increases in mortality and morbidity have been previously reported, yet no comprehensive assessment of disease burden has been done. Therefore, we aimed to estimate the global and regional burden due to non-optimal temperature exposure. METHODS: In part 1 of this study, we linked deaths to daily temperature estimates from the ERA5 reanalysis dataset. We modelled the cause-specific relative risks for 176 individual causes of death along daily temperature and 23 mean temperature zones using a two-dimensional spline within a Bayesian meta-regression framework. We then calculated the cause-specific and total temperature-attributable burden for the countries for which daily mortality data were available. In part 2, we applied cause-specific relative risks from part 1 to all locations globally. We combined exposure-response curves with daily gridded temperature and calculated the cause-specific burden based on the underlying burden of disease from the Global Burden of Diseases, Injuries, and Risk Factors Study, for the years 1990-2019. Uncertainty from all components of the modelling chain, including risks, temperature exposure, and theoretical minimum risk exposure levels, defined as the temperature of minimum mortality across all included causes, was propagated using posterior simulation of 1000 draws. FINDINGS: We included 64·9 million individual International Classification of Diseases-coded deaths from nine different countries, occurring between Jan 1, 1980, and Dec 31, 2016. 17 causes of death met the inclusion criteria. Ischaemic heart disease, stroke, cardiomyopathy and myocarditis, hypertensive heart disease, diabetes, chronic kidney disease, lower respiratory infection, and chronic obstructive pulmonary disease showed J-shaped relationships with daily temperature, whereas the risk of external causes (eg, homicide, suicide, drowning, and related to disasters, mechanical, transport, and other unintentional injuries) increased monotonically with temperature. The theoretical minimum risk exposure levels varied by location and year as a function of the underlying cause of death composition. Estimates for non-optimal temperature ranged from 7·98 deaths (95% uncertainty interval 7·10-8·85) per 100 000 and a population attributable fraction (PAF) of 1·2% (1·1-1·4) in Brazil to 35·1 deaths (29·9-40·3) per 100 000 and a PAF of 4·7% (4·3-5·1) in China. In 2019, the average cold-attributable mortality exceeded heat-attributable mortality in all countries for which data were available. Cold effects were most pronounced in China with PAFs of 4·3% (3·9-4·7) and attributable rates of 32·0 deaths (27·2-36·8) per 100 000 and in New Zealand with 3·4% (2·9-3·9) and 26·4 deaths (22·1-30·2). Heat effects were most pronounced in China with PAFs of 0·4% (0·3-0·6) and attributable rates of 3·25 deaths (2·39-4·24) per 100 000 and in Brazil with 0·4% (0·3-0·5) and 2·71 deaths (2·15-3·37). When applying our framework to all countries globally, we estimated that 1·69 million (1·52-1·83) deaths were attributable to non-optimal temperature globally in 2019. The highest heat-attributable burdens were observed in south and southeast Asia, sub-Saharan Africa, and North Africa and the Middle East, and the highest cold-attributable burdens in eastern and central Europe, and central Asia. INTERPRETATION: Acute heat and cold exposure can increase or decrease the risk of mortality for a diverse set of causes of death. Although in most regions cold effects dominate, locations with high prevailing temperatures can exhibit substantial heat effects far exceeding cold-attributable burden. Particularly, a high burden of external causes of death contributed to strong heat impacts, but cardiorespiratory diseases and metabolic diseases could also be substantial contributors. Changes in both exposures and the composition of causes of death drove changes in risk over time. Steady increases in exposure to the risk of high temperature are of increasing concern for health. FUNDING: Bill & Melinda Gates Foundation.

The prevalence of onchocerciasis in Africa and Yemen, 2000-2018: a geospatial analysis.

BACKGROUND: Onchocerciasis is a disease caused by infection with Onchocerca volvulus, which is transmitted to humans via the bite of several species of black fly, and is responsible for permanent blindness or vision loss, as well as severe skin disease. Predominantly endemic in parts of Africa and Yemen, preventive chemotherapy with mass drug administration of ivermectin is the primary intervention recommended for the elimination of its transmission. METHODS: A dataset of 18,116 geo-referenced prevalence survey datapoints was used to model annual 2000-2018 infection prevalence in Africa and Yemen. Using Bayesian model-based geostatistics, we generated spatially continuous estimates of all-age 2000-2018 onchocerciasis infection prevalence at the 5 × 5-km resolution as well as aggregations to the national level, along with corresponding estimates of the uncertainty in these predictions. RESULTS: As of 2018, the prevalence of onchocerciasis infection continues to be concentrated across central and western Africa, with the highest mean estimates at the national level in Ghana (12.2%, 95% uncertainty interval [UI] 5.0-22.7). Mean estimates exceed 5% infection prevalence at the national level for Cameroon, Central African Republic, Democratic Republic of the Congo (DRC), Guinea-Bissau, Sierra Leone, and South Sudan. CONCLUSIONS: Our analysis suggests that onchocerciasis infection has declined over the last two decades throughout western and central Africa. Focal areas of Angola, Cameroon, the Democratic Republic of the Congo, Ethiopia, Ghana, Guinea, Mali, Nigeria, South Sudan, and Uganda continue to have mean microfiladermia prevalence estimates exceeding 25%. At and above this level, the continuation or initiation of mass drug administration with ivermectin is supported. If national programs aim to eliminate onchocerciasis infection, additional surveillance or supervision of areas of predicted high prevalence would be warranted to ensure sufficiently high coverage of program interventions.

Progress towards the 2020 milestones of the end TB strategy in Cambodia: estimates of age and sex specific TB incidence and mortality from the Global Burden of Disease Study 2019.

BACKGROUND: Cambodia was recently removed from the World Health Organization's (WHO's) top 30 high tuberculosis (TB) burden countries. However, Cambodia's TB burden remains substantial, and the country is on the WHO's new global TB watchlist. We aimed to examine the levels and trends in the fatal and non-fatal TB burden in Cambodia from 1990 to 2019, assessing progress towards the WHO End TB interim milestones, which aim to reduce TB incidence rate by 20% and TB deaths by 35% from 2015 to 2020. METHODS: We leveraged the Global Burden of Disease 2019 (GBD 2019) analytical framework to compute age- and sex-specific TB mortality and incidence by HIV status in Cambodia. We enumerated TB mortality utilizing a Bayesian hierarchical Cause of Death Ensemble modeling platform. We analyzed all available data sources, including prevalence surveys, population-based tuberculin surveys, and TB cause-specific mortality, to produce internally consistent estimates of incidence and mortality using a compartmental meta-regression tool (DisMod-MR 2.1). We further estimated the fraction of tuberculosis mortality among individuals without HIV coinfection attributable to the independent effects of alcohol use, smoking, and diabetes. RESULTS: In 2019, there were 6500 (95% uncertainty interval 4830-8680) deaths due to all-form TB and 50.0 (43.8-57.8) thousand all-form TB incident cases in Cambodia. The corresponding age-standardized rates were 53.3 (39.9-69.4) per 100,000 population for mortality and 330.5 (289.0-378.6) per 100,000 population for incidence. From 2015 to 2019, the number of all-form TB deaths decreased by 11.8% (2.3-21.1), while the age-standardized all-form TB incidence rate decreased by 11.1% (6.3-15.6). Among individuals without HIV coinfection in 2019, alcohol use accounted for 28.1% (18.2-37.9) of TB deaths, smoking accounted for 27.0% (20.2-33.3), and diabetes accounted for 12.5% (7.1-19.0). Removing the combined effects of these risk factors would reduce all-form TB deaths by 54.2% (44.2-62.2). DISCUSSION: Despite significant progress in reducing TB morbidity and mortality since 1990, Cambodia is not on track to achieve the 2020 WHO End TB interim milestones. Existing programs in Cambodia can benefit from liaising with risk factor control initiatives to accelerate progress toward eliminating TB in Cambodia.

Growing up and moving out: Migration and the demographic transition in low- and middle-income nations.

International migration has increased since 1990, with increasing numbers of migrants originating from low- and middle-income countries (LMICs). Efforts to explain this compositional shift have focused on wage gaps and other push and pull factors but have not adequately considered the role of demographic factors. In many LMICs, child mortality has fallen without commensurate economic growth and amid high fertility. This combination increases young adult populations and is associated with greater outmigration: in the poorest countries, we estimate that a one-percentage-point increase in the five-year lagged growth rate of the population of 15-24-year-olds was associated with a 15 per cent increase in all-age outmigrants, controlling for other factors. Increases in growth of young adult populations led to 20.4 million additional outmigrants across 80 countries between 1990 and 2015. Understanding the determinants of these migration shifts should help policymakers in origin and destination countries to maximize their potential positive effects.

Global, Regional, and National Burden of Calcific Aortic Valve and Degenerative Mitral Valve Diseases, 1990-2017.

BACKGROUND: Nonrheumatic valvular diseases are common; however, no studies have estimated their global or national burden. As part of the Global Burden of Disease Study 2017, mortality, prevalence, and disability-adjusted life-years (DALYs) for calcific aortic valve disease (CAVD), degenerative mitral valve disease, and other nonrheumatic valvular diseases were estimated for 195 countries and territories from 1990 to 2017. METHODS: Vital registration data, epidemiologic survey data, and administrative hospital data were used to estimate disease burden using the Global Burden of Disease Study modeling framework, which ensures comparability across locations. Geospatial statistical methods were used to estimate disease for all countries, because data on nonrheumatic valvular diseases are extremely limited for some regions of the world, such as Sub-Saharan Africa and South Asia. Results accounted for estimated level of disease severity as well as the estimated availability of valve repair or replacement procedures. DALYs and other measures of health-related burden were generated for both sexes and each 5-year age group, location, and year from 1990 to 2017. RESULTS: Globally, CAVD and degenerative mitral valve disease caused 102 700 (95% uncertainty interval [UI], 82 700-107 900) and 35 700 (95% UI, 30 500-42 500) deaths, and 12.6 million (95% UI, 11.4 million-13.8 million) and 18.1 million (95% UI, 17.6 million-18.6 million) prevalent cases existed in 2017, respectively. A total of 2.5 million (95% UI, 2.3 million-2.8 million) DALYs were estimated as caused by nonrheumatic valvular diseases globally, representing 0.10% (95% UI, 0.09%-0.11%) of total lost health from all diseases in 2017. The number of DALYs increased for CAVD and degenerative mitral valve disease between 1990 and 2017 by 101% (95% UI, 79%-117%) and 35% (95% UI, 23%-47%), respectively. There is significant geographic variation in the prevalence, mortality rate, and overall burden of these diseases, with highest age-standardized DALY rates of CAVD estimated for high-income countries. CONCLUSIONS: These global and national estimates demonstrate that CAVD and degenerative mitral valve disease are important causes of disease burden among older adults. Efforts to clarify modifiable risk factors and improve access to valve interventions are necessary if progress is to be made toward reducing, and eventually eliminating, the burden of these highly treatable diseases.

Fertility, mortality, migration, and population scenarios for 195 countries and territories from 2017 to 2100: a forecasting analysis for the Global Burden of Disease Study.

BACKGROUND: Understanding potential patterns in future population levels is crucial for anticipating and planning for changing age structures, resource and health-care needs, and environmental and economic landscapes. Future fertility patterns are a key input to estimation of future population size, but they are surrounded by substantial uncertainty and diverging methodologies of estimation and forecasting, leading to important differences in global population projections. Changing population size and age structure might have profound economic, social, and geopolitical impacts in many countries. In this study, we developed novel methods for forecasting mortality, fertility, migration, and population. We also assessed potential economic and geopolitical effects of future demographic shifts. METHODS: We modelled future population in reference and alternative scenarios as a function of fertility, migration, and mortality rates. We developed statistical models for completed cohort fertility at age 50 years (CCF50). Completed cohort fertility is much more stable over time than the period measure of the total fertility rate (TFR). We modelled CCF50 as a time-series random walk function of educational attainment and contraceptive met need. Age-specific fertility rates were modelled as a function of CCF50 and covariates. We modelled age-specific mortality to 2100 using underlying mortality, a risk factor scalar, and an autoregressive integrated moving average (ARIMA) model. Net migration was modelled as a function of the Socio-demographic Index, crude population growth rate, and deaths from war and natural disasters; and use of an ARIMA model. The model framework was used to develop a reference scenario and alternative scenarios based on the pace of change in educational attainment and contraceptive met need. We estimated the size of gross domestic product for each country and territory in the reference scenario. Forecast uncertainty intervals (UIs) incorporated uncertainty propagated from past data inputs, model estimation, and forecast data distributions. FINDINGS: The global TFR in the reference scenario was forecasted to be 1·66 (95% UI 1·33-2·08) in 2100. In the reference scenario, the global population was projected to peak in 2064 at 9·73 billion (8·84-10·9) people and decline to 8·79 billion (6·83-11·8) in 2100. The reference projections for the five largest countries in 2100 were India (1·09 billion [0·72-1·71], Nigeria (791 million [594-1056]), China (732 million [456-1499]), the USA (336 million [248-456]), and Pakistan (248 million [151-427]). Findings also suggest a shifting age structure in many parts of the world, with 2·37 billion (1·91-2·87) individuals older than 65 years and 1·70 billion (1·11-2·81) individuals younger than 20 years, forecasted globally in 2100. By 2050, 151 countries were forecasted to have a TFR lower than the replacement level (TFR <2·1), and 183 were forecasted to have a TFR lower than replacement by 2100. 23 countries in the reference scenario, including Japan, Thailand, and Spain, were forecasted to have population declines greater than 50% from 2017 to 2100; China's population was forecasted to decline by 48·0% (-6·1 to 68·4). China was forecasted to become the largest economy by 2035 but in the reference scenario, the USA was forecasted to once again become the largest economy in 2098. Our alternative scenarios suggest that meeting the Sustainable Development Goals targets for education and contraceptive met need would result in a global population of 6·29 billion (4·82-8·73) in 2100 and a population of 6·88 billion (5·27-9·51) when assuming 99th percentile rates of change in these drivers. INTERPRETATION: Our findings suggest that continued trends in female educational attainment and access to contraception will hasten declines in fertility and slow population growth. A sustained TFR lower than the replacement level in many countries, including China and India, would have economic, social, environmental, and geopolitical consequences. Policy options to adapt to continued low fertility, while sustaining and enhancing female reproductive health, will be crucial in the years to come. FUNDING: Bill & Melinda Gates Foundation.

Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study.

BACKGROUND: Sepsis is life-threatening organ dysfunction due to a dysregulated host response to infection. It is considered a major cause of health loss, but data for the global burden of sepsis are limited. As a syndrome caused by underlying infection, sepsis is not part of standard Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimates. Accurate estimates are important to inform and monitor health policy interventions, allocation of resources, and clinical treatment initiatives. We estimated the global, regional, and national incidence of sepsis and mortality from this disorder using data from GBD 2017. METHODS: We used multiple cause-of-death data from 109 million individual death records to calculate mortality related to sepsis among each of the 282 underlying causes of death in GBD 2017. The percentage of sepsis-related deaths by underlying GBD cause in each location worldwide was modelled using mixed-effects linear regression. Sepsis-related mortality for each age group, sex, location, GBD cause, and year (1990-2017) was estimated by applying modelled cause-specific fractions to GBD 2017 cause-of-death estimates. We used data for 8·7 million individual hospital records to calculate in-hospital sepsis-associated case-fatality, stratified by underlying GBD cause. In-hospital sepsis-associated case-fatality was modelled for each location using linear regression, and sepsis incidence was estimated by applying modelled case-fatality to sepsis-related mortality estimates. FINDINGS: In 2017, an estimated 48·9 million (95% uncertainty interval [UI] 38·9-62·9) incident cases of sepsis were recorded worldwide and 11·0 million (10·1-12·0) sepsis-related deaths were reported, representing 19·7% (18·2-21·4) of all global deaths. Age-standardised sepsis incidence fell by 37·0% (95% UI 11·8-54·5) and mortality decreased by 52·8% (47·7-57·5) from 1990 to 2017. Sepsis incidence and mortality varied substantially across regions, with the highest burden in sub-Saharan Africa, Oceania, south Asia, east Asia, and southeast Asia. INTERPRETATION: Despite declining age-standardised incidence and mortality, sepsis remains a major cause of health loss worldwide and has an especially high health-related burden in sub-Saharan Africa. FUNDING: The Bill & Melinda Gates Foundation, the National Institutes of Health, the University of Pittsburgh, the British Columbia Children's Hospital Foundation, the Wellcome Trust, and the Fleming Fund.

Variation in Childhood Diarrheal Morbidity and Mortality in Africa, 2000-2015.

BACKGROUND: Diarrheal diseases are the third leading cause of disease and death in children younger than 5 years of age in Africa and were responsible for an estimated 30 million cases of severe diarrhea (95% credible interval, 27 million to 33 million) and 330,000 deaths (95% credible interval, 270,000 to 380,000) in 2015. The development of targeted approaches to address this burden has been hampered by a paucity of comprehensive, fine-scale estimates of diarrhea-related disease and death among and within countries. METHODS: We produced annual estimates of the prevalence and incidence of diarrhea and diarrhea-related mortality with high geographic detail (5 km2) across Africa from 2000 through 2015. Estimates were created with the use of Bayesian geostatistical techniques and were calibrated to the results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016. RESULTS: The results revealed geographic inequality with regard to diarrhea risk in Africa. Of the estimated 330,000 childhood deaths that were attributable to diarrhea in 2015, more than 50% occurred in 55 of the 782 first-level administrative subdivisions (e.g., states). In 2015, mortality rates among first-level administrative subdivisions in Nigeria differed by up to a factor of 6. The case fatality rates were highly varied at the national level across Africa, with the highest values observed in Benin, Lesotho, Mali, Nigeria, and Sierra Leone. CONCLUSIONS: Our findings showed concentrated areas of diarrheal disease and diarrhea-related death in countries that had a consistently high burden as well as in countries that had considerable national-level reductions in diarrhea burden. (Funded by the Bill and Melinda Gates Foundation.).