Global, regional, and national burden of hepatitis B, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: Combating viral hepatitis is part of the UN Sustainable Development Goals (SDGs), and WHO has put forth hepatitis B elimination targets in its Global Health Sector Strategy on Viral Hepatitis (WHO-GHSS) and Interim Guidance for Country Validation of Viral Hepatitis Elimination (WHO Interim Guidance). We estimated the global, regional, and national prevalence of hepatitis B virus (HBV), as well as mortality and disability-adjusted life-years (DALYs) due to HBV, as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. This included estimates for 194 WHO member states, for which we compared our estimates to WHO elimination targets.  Methods: The primary data sources were population-based serosurveys, claims and hospital discharges, cancer registries, vital registration systems, and published case series. We estimated chronic HBV infection and the burden of HBV-related diseases, defined as an aggregate of cirrhosis due to hepatitis B, liver cancer due to hepatitis B, and acute hepatitis B. We used DisMod-MR 2.1, a Bayesian mixed-effects meta-regression tool, to estimate the prevalence of chronic HBV infection, cirrhosis, and aetiological proportions of cirrhosis. We used mortality-to-incidence ratios modelled with spatiotemporal Gaussian process regression to estimate the incidence of liver cancer. We used the Cause of Death Ensemble modelling (CODEm) model, a tool that selects models and covariates on the basis of out-of-sample performance, to estimate mortality due to cirrhosis, liver cancer, and acute hepatitis B.  Findings: In 2019, the estimated global, all-age prevalence of chronic HBV infection was 4·1% (95% uncertainty interval [UI] 3·7 to 4·5), corresponding to 316 million (284 to 351) infected people. There was a 31·3% (29·0 to 33·9) decline in all-age prevalence between 1990 and 2019, with a more marked decline of 76·8% (76·2 to 77·5) in prevalence in children younger than 5 years. HBV-related diseases resulted in 555 000 global deaths (487 000 to 630 000) in 2019. The number of HBV-related deaths increased between 1990 and 2019 (by 5·9% [–5·6 to 19·2]) and between 2015 and 2019 (by 2·9% [–5·9 to 11·3]). By contrast, all-age and age-standardised death rates due to HBV-related diseases decreased during these periods. We compared estimates for 2019 in 194 WHO locations to WHO-GHSS 2020 targets, and found that four countries achieved a 10% reduction in deaths, 15 countries achieved a 30% reduction in new cases, and 147 countries achieved a 1% prevalence in children younger than 5 years. As of 2019, 68 of 194 countries had already achieved the 2030 target proposed in WHO Interim Guidance of an all-age HBV-related death rate of four per 100 000.  Interpretation: The prevalence of chronic HBV infection declined over time, particularly in children younger than 5 years, since the introduction of hepatitis B vaccination. HBV-related death rates also decreased, but HBV-related death counts increased as a result of population growth, ageing, and cohort effects. By 2019, many countries had met the interim seroprevalence target for children younger than 5 years, but few countries had met the WHO-GHSS interim targets for deaths and new cases. Progress according to all indicators must be accelerated to meet 2030 targets, and there are marked disparities in burden and progress across the world. HBV interventions, such as vaccination, testing, and treatment, must be strategically supported and scaled up to achieve elimination. </p

Five insights from the Global Burden of Disease Study 2019

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3·5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950–2019: A comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019. Interpretation: Over the past 20 years, fertility rates have been dropping steadily and life expectancy has been increasing, with few exceptions. Much of this change follows historical patterns linking social and economic determinants, such as those captured by the GBD Socio-demographic Index, with demographic outcomes. More recently, several countries have experienced a combination of low fertility and stagnating improvement in mortality rates, pushing more populations into the late stages of the demographic transition. Tracking demographic change and the emergence of new patterns will be essential for global health monitoring. Funding: Bill & Melinda Gates Foundation

Cancer Incidence, Mortality, Years of Life Lost, Years Lived with Disability, and Disability-Adjusted Life Years for 29 Cancer Groups from 2010 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019

Importance The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden.  Objective To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019.  Evidence Review  The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs).  Findings In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles. Conclusions and Relevance The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world..</p

Author Correction: Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017 (Nature Medicine, (2020), 26, 5, (750-759), 10.1038/s41591-020-0807-6)

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000-17: Analysis for the Global Burden of Disease Study 2017

Background Across low-income and middle-income countries (LMICs), one in ten deaths in children younger than 5 years is attributable to diarrhoea. The substantial between-country variation in both diarrhoea incidence and mortality is attributable to interventions that protect children, prevent infection, and treat disease. Identifying subnational regions with the highest burden and mapping associated risk factors can aid in reducing preventable childhood diarrhoea. Methods We used Bayesian model-based geostatistics and a geolocated dataset comprising 15 072 746 children younger than 5 years from 466 surveys in 94 LMICs, in combination with findings of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, to estimate posterior distributions of diarrhoea prevalence, incidence, and mortality from 2000 to 2017. From these data, we estimated the burden of diarrhoea at varying subnational levels (termed units) by spatially aggregating draws, and we investigated the drivers of subnational patterns by creating aggregated risk factor estimates. Findings The greatest declines in diarrhoeal mortality were seen in south and southeast Asia and South America, where 54·0% (95% uncertainty interval [UI] 38·1-65·8), 17·4% (7·7-28·4), and 59·5% (34·2-86·9) of units, respectively, recorded decreases in deaths from diarrhoea greater than 10%. Although children in much of Africa remain at high risk of death due to diarrhoea, regions with the most deaths were outside Africa, with the highest mortality units located in Pakistan. Indonesia showed the greatest within-country geographical inequality; some regions had mortality rates nearly four times the average country rate. Reductions in mortality were correlated to improvements in water, sanitation, and hygiene (WASH) or reductions in child growth failure (CGF). Similarly, most high-risk areas had poor WASH, high CGF, or low oral rehydration therapy coverage. Interpretation By co-analysing geospatial trends in diarrhoeal burden and its key risk factors, we could assess candidate drivers of subnational death reduction. Further, by doing a counterfactual analysis of the remaining disease burden using key risk factors, we identified potential intervention strategies for vulnerable populations. In view of the demands for limited resources in LMICs, accurately quantifying the burden of diarrhoea and its drivers is important for precision public health

Mapping geographical inequalities in oral rehydration therapy coverage in low-income and middle-income countries, 2000-17

Background: Oral rehydration solution (ORS) is a form of oral rehydration therapy (ORT) for diarrhoea that has the potential to drastically reduce child mortality; yet, according to UNICEF estimates, less than half of children younger than 5 years with diarrhoea in low-income and middle-income countries (LMICs) received ORS in 2016. A variety of recommended home fluids (RHF) exist as alternative forms of ORT; however, it is unclear whether RHF prevent child mortality. Previous studies have shown considerable variation between countries in ORS and RHF use, but subnational variation is unknown. This study aims to produce high-resolution geospatial estimates of relative and absolute coverage of ORS, RHF, and ORT (use of either ORS or RHF) in LMICs. Methods: We used a Bayesian geostatistical model including 15 spatial covariates and data from 385 household surveys across 94 LMICs to estimate annual proportions of children younger than 5 years of age with diarrhoea who received ORS or RHF (or both) on continuous continent-wide surfaces in 2000–17, and aggregated results to policy-relevant administrative units. Additionally, we analysed geographical inequality in coverage across administrative units and estimated the number of diarrhoeal deaths averted by increased coverage over the study period. Uncertainty in the mean coverage estimates was calculated by taking 250 draws from the posterior joint distribution of the model and creating uncertainty intervals (UIs) with the 2·5th and 97·5th percentiles of those 250 draws. Findings: While ORS use among children with diarrhoea increased in some countries from 2000 to 2017, coverage remained below 50% in the majority (62·6%; 12 417 of 19 823) of second administrative-level units and an estimated 6 519 000 children (95% UI 5 254 000–7 733 000) with diarrhoea were not treated with any form of ORT in 2017. Increases in ORS use corresponded with declines in RHF in many locations, resulting in relatively constant overall ORT coverage from 2000 to 2017. Although ORS was uniformly distributed subnationally in some countries, within-country geographical inequalities persisted in others; 11 countries had at least a 50% difference in one of their units compared with the country mean. Increases in ORS use over time were correlated with declines in RHF use and in diarrhoeal mortality in many locations, and an estimated 52 230 diarrhoeal deaths (36 910–68 860) were averted by scaling up of ORS coverage between 2000 and 2017. Finally, we identified key subnational areas in Colombia, Nigeria, and Sudan as examples of where diarrhoeal mortality remains higher than average, while ORS coverage remains lower than average. Interpretation: To our knowledge, this study is the first to produce and map subnational estimates of ORS, RHF, and ORT coverage and attributable child diarrhoeal deaths across LMICs from 2000 to 2017, allowing for tracking progress over time. Our novel results, combined with detailed subnational estimates of diarrhoeal morbidity and mortality, can support subnational needs assessments aimed at furthering policy makers' understanding of within-country disparities. Over 50 years after the discovery that led to this simple, cheap, and life-saving therapy, large gains in reducing mortality could still be made by reducing geographical inequalities in ORS coverage. Funding: Bill & Melinda Gates Foundation

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic

The global distribution of lymphatic filariasis, 2000–18: a geospatial analysis

Background: Lymphatic filariasis is a neglected tropical disease that can cause permanent disability through disruption of the lymphatic system. This disease is caused by parasitic filarial worms that are transmitted by mosquitos. Mass drug administration (MDA) of antihelmintics is recommended by WHO to eliminate lymphatic filariasis as a public health problem. This study aims to produce the first geospatial estimates of the global prevalence of lymphatic filariasis infection over time, to quantify progress towards elimination, and to identify geographical variation in distribution of infection. Methods: A global dataset of georeferenced surveyed locations was used to model annual 2000–18 lymphatic filariasis prevalence for 73 current or previously endemic countries. We applied Bayesian model-based geostatistics and time series methods to generate spatially continuous estimates of global all-age 2000–18 prevalence of lymphatic filariasis infection mapped at a resolution of 5 km2 and aggregated to estimate total number of individuals infected. Findings: We used 14 927 datapoints to fit the geospatial models. An estimated 199 million total individuals (95% uncertainty interval 174–234 million) worldwide were infected with lymphatic filariasis in 2000, with totals for WHO regions ranging from 3·1 million (1·6–5·7 million) in the region of the Americas to 107 million (91–134 million) in the South-East Asia region. By 2018, an estimated 51 million individuals (43–63 million) were infected. Broad declines in prevalence are observed globally, but focal areas in Africa and southeast Asia remain less likely to have attained infection prevalence thresholds proposed to achieve local elimination. Interpretation: Although the prevalence of lymphatic filariasis infection has declined since 2000, MDA is still necessary across large populations in Africa and Asia. Our mapped estimates can be used to identify areas where the probability of meeting infection thresholds is low, and when coupled with large uncertainty in the predictions, indicate additional data collection or intervention might be warranted before MDA programmes cease. Funding: Bill & Melinda Gates Foundation