The burden of bacterial antimicrobial resistance in the WHO European region in 2019: a cross-country systematic analysis

Background: Antimicrobial resistance (AMR) represents one of the most crucial threats to public health and modern health care. Previous studies have identified challenges with estimating the magnitude of the problem and its downstream effect on human health and mortality. To our knowledge, this study presents the most comprehensive set of regional and country-level estimates of AMR burden in the WHO European region to date.  Methods: We estimated deaths and disability-adjusted life-years attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen–drug combinations for the WHO European region and its countries in 2019. Our methodological approach consisted of five broad components: the number of deaths in which infection had a role, the proportion of infectious deaths attributable to a given infectious syndrome, the proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antimicrobial drug of interest, and the excess risk of mortality (or duration of an infection) associated with this resistance. These components were then used to estimate the disease burden by using two counterfactual scenarios: deaths attributable to AMR (considering an alternative scenario where infections with resistant pathogens are replaced with susceptible ones) and deaths associated with AMR (considering an alternative scenario where drug-resistant infections would not occur at all). Data were solicited from a wide array of international stakeholders; these included research hospitals, surveillance networks, and infection databases maintained by private laboratories and medical technology companies. We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity.  Findings: We estimated 541 000 deaths (95% UI 370 000–763 000) associated with bacterial AMR and 133 000 deaths (90 100–188 000) attributable to bacterial AMR in the whole WHO European region in 2019. The largest fatal burden of AMR in the region came from bloodstream infections, with 195 000 deaths (104 000–333 000) associated with resistance, followed by intra-abdominal infections (127 000 deaths [81 900–185 000]) and respiratory infections (120 000 deaths [94 500–154 000]). Seven leading pathogens were responsible for about 457 000 deaths associated with resistance in 53 countries of this region; these pathogens were, in descending order of mortality, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecium, Streptococcus pneumoniae, and Acinetobacter baumannii. Methicillin-resistant S aureus was shown to be the leading pathogen–drug combination in 27 countries for deaths attributable to AMR, while aminopenicillin-resistant E coli predominated in 47 countries for deaths associated with AMR.  Interpretation: The high levels of resistance for several important bacterial pathogens and pathogen–drug combinations, together with the high mortality rates associated with these pathogens, show that AMR is a serious threat to public health in the WHO European region. Our regional and cross-country analyses open the door for strategies that can be tailored to leading pathogen–drug combinations and the available resources in a specific location. These results underscore that the most effective way to tackle AMR in this region will require targeted efforts and investments in conjunction with continuous outcome-based research endeavours. </p

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

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

Measuring progress and projecting attainment on the basis of past trends of the health-related Sustainable Development Goals in 188 countries: an analysis from the Global Burden of Disease Study 2016

Background The UN's Sustainable Development Goals (SDGs) are grounded in the global ambition of “leaving no one behind”. Understanding today's gains and gaps for the health-related SDGs is essential for decision makers as they aim to improve the health of populations. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016), we measured 37 of the 50 health-related SDG indicators over the period 1990–2016 for 188 countries, and then on the basis of these past trends, we projected indicators to 2030. Methods We used standardised GBD 2016 methods to measure 37 health-related indicators from 1990 to 2016, an increase of four indicators since GBD 2015. We substantially revised the universal health coverage (UHC) measure, which focuses on coverage of essential health services, to also represent personal health-care access and quality for several non-communicable diseases. We transformed each indicator on a scale of 0–100, with 0 as the 2·5th percentile estimated between 1990 and 2030, and 100 as the 97·5th percentile during that time. An index representing all 37 health-related SDG indicators was constructed by taking the geometric mean of scaled indicators by target. On the basis of past trends, we produced projections of indicator values, using a weighted average of the indicator and country-specific annualised rates of change from 1990 to 2016 with weights for each annual rate of change based on out-of-sample validity. 24 of the currently measured health-related SDG indicators have defined SDG targets, against which we assessed attainment. Findings Globally, the median health-related SDG index was 56·7 (IQR 31·9–66·8) in 2016 and country-level performance markedly varied, with Singapore (86·8, 95% uncertainty interval 84·6–88·9), Iceland (86·0, 84·1–87·6), and Sweden (85·6, 81·8–87·8) having the highest levels in 2016 and Afghanistan (10·9, 9·6–11·9), the Central African Republic (11·0, 8·8–13·8), and Somalia (11·3, 9·5–13·1) recording the lowest. Between 2000 and 2016, notable improvements in the UHC index were achieved by several countries, including Cambodia, Rwanda, Equatorial Guinea, Laos, Turkey, and China; however, a number of countries, such as Lesotho and the Central African Republic, but also high-income countries, such as the USA, showed minimal gains. Based on projections of past trends, the median number of SDG targets attained in 2030 was five (IQR 2–8) of the 24 defined targets currently measured. Globally, projected target attainment considerably varied by SDG indicator, ranging from more than 60% of countries projected to reach targets for under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria, to less than 5% of countries projected to achieve targets linked to 11 indicator targets, including those for childhood overweight, tuberculosis, and road injury mortality. For several of the health-related SDGs, meeting defined targets hinges upon substantially faster progress than what most countries have achieved in the past. Interpretation GBD 2016 provides an updated and expanded evidence base on where the world currently stands in terms of the health-related SDGs. Our improved measure of UHC offers a basis to monitor the expansion of health services necessary to meet the SDGs. Based on past rates of progress, many places are facing challenges in meeting defined health-related SDG targets, particularly among countries that are the worst off. In view of the early stages of SDG implementation, however, opportunity remains to take actions to accelerate progress, as shown by the catalytic effects of adopting the Millennium Development Goals after 2000. With the SDGs' broader, bolder development agenda, multisectoral commitments and investments are vital to make the health-related SDGs within reach of all populations. Funding Bill & Melinda Gates Foundation