Project description:BackgroundAntimicrobial 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.MethodsWe 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.FindingsWe 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.InterpretationThe 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.FundingBill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.

Project description:BackgroundA critical and persistent challenge to global health and modern health care is the threat of antimicrobial resistance (AMR). Previous studies have reported a disproportionate burden of AMR in low-income and middle-income countries, but there remains an urgent need for more in-depth analyses across Africa. This study presents one of the most comprehensive sets of regional and country-level estimates of bacterial AMR burden in the WHO African region to date.MethodsWe estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen-drug combinations for countries in the WHO African region 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). We obtained data from 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.FindingsIn the WHO African region in 2019, there were an estimated 1·05 million deaths (95% UI 829 000-1 316 000) associated with bacterial AMR and 250 000 deaths (192 000-325 000) attributable to bacterial AMR. The largest fatal AMR burden was attributed to lower respiratory and thorax infections (119 000 deaths [92 000-151 000], or 48% of all estimated bacterial pathogen AMR deaths), bloodstream infections (56 000 deaths [37 000-82 000], or 22%), intra-abdominal infections (26 000 deaths [17 000-39 000], or 10%), and tuberculosis (18 000 deaths [3850-39 000], or 7%). Seven leading pathogens were collectively responsible for 821 000 deaths (636 000-1 051 000) associated with resistance in this region, with four pathogens exceeding 100 000 deaths each: Streptococcus pneumoniae, Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus. Third-generation cephalosporin-resistant K pneumoniae and meticillin-resistant S aureus were shown to be the leading pathogen-drug combinations in 25 and 16 countries, respectively (53% and 34% of the whole region, comprising 47 countries) for deaths attributable to AMR.InterpretationThis study reveals a high level of AMR burden for several bacterial pathogens and pathogen-drug combinations in the WHO African region. The high mortality rates associated with these pathogens demonstrate an urgent need to address the burden of AMR in Africa. These estimates also show that quality and access to health care and safe water and sanitation are correlated with AMR mortality, with a higher fatal burden found in lower resource settings. Our cross-country analyses within this region can help local governments to leverage domestic and global funding to create stewardship policies that target the leading pathogen-drug combinations.FundingBill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.

Project description:BackgroundHigh prevalence of diabetes has been reported in the Americas, but no comprehensive analysis of diabetes burden and related factors for the region is available. We aimed to describe the burden of type 1 and type 2 diabetes and that of hyperglycaemia in the Americas from 1990 to 2019.MethodsWe used estimates from GBD 2019 to evaluate the burden of diabetes in adults aged 20 years or older and high fasting plasma glucose in adults aged 25 years or older in the 39 countries and territories of the six regions in the Americas from 1990 to 2019. The main source to estimate the mortality attributable to diabetes and to chronic kidney disease due to diabetes was vital registration. Mortality due to overall diabetes (ie, diabetes and diabetes due to chronic kidney disease) was estimated using the Cause of Death Ensemble model. Years of life lost (YLLs) were calculated as the number of deaths multiplied by standard life expectancy at the age that the death occurred, years lived with disability (YLDs) were estimated based on the prevalence and severity of complications of diabetes. Disability-adjusted life-years (DALYs) were estimated as a sum of YLDs and YLLs. We assessed the association of diabetes burden with the level of development of a country (according to the Socio-demographic Index), health-care access and quality (estimated with the Healthcare Access and Quality Index), and diabetes prevalence. We also calculated the population attributable fraction (PAF) of diabetes burden due to each of its risk factors. We report the 95% uncertainty intervals for all estimates.FindingsIn 2019, an estimated total of 409 000 (95% uncertainty interval 373 000-443 000) adults aged 20 years or older in the Americas died from diabetes, which represented 5·9% of all deaths. Diabetes was responsible for 2266 (1930-2649) crude DALYs per 100 000 adults in the Americas, and high fasting plasma glucose for 4401 DALYs (3685-5265) per 100 000 adults, with large variation across regions. DALYs were mostly due to type 2 diabetes and distribution was heterogeneous, being highest in central Latin America and the Caribbean and lowest in high-income North America and southern Latin America. Between 1990 and 2019, age-standardised DALYs due to type 2 diabetes increased 27·4% (22·0-32·5). This increase was particularly high in Andean Latin America and high-income North America. Burden for both type 1 and type 2 diabetes across countries increased with higher diabetes prevalence and decreased with greater Socio-demographic and Healthcare Access and Quality Indices. Main risk factors for the burden were high BMI, with a PAF of 63·2% and dietary risks, with a PAF of 27·5%. The fraction of burden due to disability has increased since 1990 and now represents nearly half of the overall burden in 2019.InterpretationThe burden of diabetes in the Americas is large, increasing, heterogeneous, and expanding. To confront the rising burden, population-based interventions aimed to reduce type 2 diabetes risk and strengthening health systems to provide effective and cost-efficient care for those affected are mandatory.FundingBill & Melinda Gates Foundation.

Project description:BackgroundInfectious diseases and antimicrobial resistance (AMR) has become pressing concerns in China. We aimed to comprehensively investigate the burden of them.MethodsData on infectious diseases and AMR were collected by the Global Antimicrobial Resistance Burden study 2019. Multinomial network meta-regression, logistic regression, and ensemble Spatiotemporal Gaussian process regression were used to fit the number and rate in DisMod-MR 2.1 modelling framework. We reported the number and rates of the disease burdens of 12 infectious syndromes by age and sex; described the burden caused by 43 pathogens; estimated the AMR burden of 22 bacteria and bacteria-antibiotics combinations.FindingsThere were an estimated 1.3 million (95% uncertainty intervals, UI 0.8-1.9) infection-related deaths, accounting for 12.1% of the total deaths in China 2019. Males were 1.5 times more affected than females. Bloodstream infections (BSIs) were most lethal infectious syndrome, associating with 521,392 deaths (286,307-870,583), followed by lower respiratory infections (373,175), and peritoneal and intra-abdominal infections (152,087). These five leading pathogens were S aureus, A baumannii, E coli, S pneumoniae, and E spp., which were associated with 41.2% (502,658/1,218,693) of all infection-related deaths. The pathogens of different infectious syndromes exhibited significant heterogeneity. In 2019, more than 600 thousand deaths were associated with AMR, including 145 thousand deaths attributable to AMR. The top 3 AMR attributable to death were carbapenems-resistance A baumannii (18,143), methicillin-resistance S aureus (16,933) and third-generation cephalosporins-resistance E coli (8032).InterpretationInfectious diseases and bacterial antimicrobial resistance were serious threat to public health in China, related to 1.3 million and more than 600 thousand deaths per-year, respectively. Antimicrobial stewardship was urgent.FundingThis work was supported by National Natural Science Foundation of China (82270626); China Mega-Project for Infectious Diseases (2017ZX10203202, 2013ZX10002005); the Project of Beijing Science and Technology Committee (Z191100007619037).

Project description:BackgroundThe suicide mortality rate in the Region of the Americas has been increasing, while decreasing in all other World Health Organization regions; highlighting the urgent need for enhanced prevention efforts. Gaining a better understanding of population-level contextual factors associated with suicide may aid such efforts. We aimed to evaluate the contextual factors associated with country-level, sex-specific suicide mortality rates in the Region of the Americas for 2000-2019.MethodsAnnual sex-specific age-standardized suicide mortality estimates were obtained from the World Health Organization (WHO) Global Health Estimates database. To investigate the sex-specific suicide mortality rate trend over time in the region, we performed joinpoint regression analysis. We then applied a linear mixed model to estimate the effects of specific contextual factors on the suicide mortality rate across countries in the region over time. All potentially relevant contextual factors, obtained from the Global Burden of Disease Study 2019 covariates and The World Bank, were selected in a step-wise manner.FindingsWe found that the mean country-level suicide mortality rate among males in the region decreased as health expenditure per capita and the proportion of the country with a moderate population density increased; and increased as the death rate due to homicide, prevalence of intravenous drug use, risk-weighted prevalence of alcohol use, and unemployment rate increased. The mean country-level suicide mortality rate among females in the region decreased as the number of employed medical doctors per 10,000 population and the proportion of the country with a moderate population density increased; and increased when relative education inequality and unemployment rate increased.InterpretationAlthough there was some overlap, the contextual factors that significantly impacted the suicide mortality rate among males and females were largely different, which mirrors the current literature on individual-level risk factors for suicide. Taken together, our data supports that sex should be considered when adapting and testing suicide risk reduction interventions, and when developing national suicide prevention strategies.FundingThis work received no funding.

Project description:BackgroundAccurate estimates of the burden of antimicrobial resistance (AMR) are needed to establish the magnitude of this global threat in terms of both health and cost, and to paramaterise cost-effectiveness evaluations of interventions aiming to tackle the problem. This review aimed to establish the alternative methodologies used in estimating AMR burden in order to appraise the current evidence base.MethodsMEDLINE, EMBASE, Scopus, EconLit, PubMed and grey literature were searched. English language studies evaluating the impact of AMR (from any microbe) on patient, payer/provider and economic burden published between January 2013 and December 2015 were included. Independent screening of title/abstracts followed by full texts was performed using pre-specified criteria. A study quality score (from zero to one) was derived using Newcastle-Ottawa and Philips checklists. Extracted study data were used to compare study method and resulting burden estimate, according to perspective. Monetary costs were converted into 2013 USD.ResultsOut of 5187 unique retrievals, 214 studies were included. One hundred eighty-seven studies estimated patient health, 75 studies estimated payer/provider and 11 studies estimated economic burden. 64% of included studies were single centre. The majority of studies estimating patient or provider/payer burden used regression techniques. 48% of studies estimating mortality burden found a significant impact from resistance, excess healthcare system costs ranged from non-significance to $1 billion per year, whilst economic burden ranged from $21,832 per case to over $3 trillion in GDP loss. Median quality scores (interquartile range) for patient, payer/provider and economic burden studies were 0.67 (0.56-0.67), 0.56 (0.46-0.67) and 0.53 (0.44-0.60) respectively.ConclusionsThis study highlights what methodological assumptions and biases can occur dependent on chosen outcome and perspective. Currently, there is considerable variability in burden estimates, which can lead in-turn to inaccurate intervention evaluations and poor policy/investment decisions. Future research should utilise the recommendations presented in this review.Trial registrationThis systematic review is registered with PROSPERO (PROSPERO CRD42016037510).

Project description:BackgroundThere are still no detailed data about the burden of bacterial antimicrobial resistance (AMR) in urinary tract infections (UTI). Concrete knowledge of global and regional bacterial AMR data is crucial for developing informed programs and policies to control bacterial AMR and for prudent use of antibiotics to optimize antibiotic therapy in patients with UTI. This study aimed to provide comprehensive global and regional estimates for the AMR burden of UTI in 2019.MethodsData were obtained from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), including death, disability-adjusted life-years (DALYs), year lived with disability (YLD), and years of life lost (YLL) for bacterial AMR in UTI for 7 GBD super-regions, 21 regions, 14 pathogens, 13 antibiotic classes, and 66 pathogen-antibiotic combinations in 2019. The estimates were based on two counterfactual scenarios: drug-susceptible infection and no infection.ResultsGlobally, there were 64.89 thousand deaths (95% uncertainty interval [UI]: 45.86-93.35) attributed to and 0.26 million deaths (95% UI: 0.18-0.36) associated with bacterial AMR in UTI in 2019. Among regions, the all-age death rates were higher in southern Latin America, tropical Latin America, and Europe and lower in sub-Saharan Africa. Escherichia coli and Klebsiella pneumoniae accounted for more than 50% of deaths attributable to and associated with AMR, and resistance was high among multiple types of antibiotic class, including fluoroquinolones, carbapenems, and third-generation cephalosporins. There were 2 pathogen-drug combinations that caused more than 6000 resistance-attributable deaths: third-generation cephalosporin-resistant Escherichia coli and fluoroquinolone-resistant Escherichia coli.ConclusionsAMR in UTI is an unignorable health problem, both for the management of urology disease and for global antibiotic resistance. Special tailored strategies, including enhanced surveillance and rational use of antibiotics, should be developed for different regions according to the region-specific pathogen-antibiotic situations and resources.

Project description:BackgroundHigh body mass index (BMI) has gradually become an increased risk factor for the global burden of diseases (GBD). As the disease burden and the number of elders globally increase, it is crucial for policymakers to realise the associations between high BMI and disease burden worldwide in a timely manner and to develop effective interventions for different countries and ages.MethodsWe used the GBD 2019 database to analyse the deaths and disability-adjusted life-years (DALYs) in the disease burden associated with high BMI and indicated the health inequality at the global, regional, and national levels. We applied the slope index of inequality and concentration index, two standard metrics of absolute and relative gradient inequality recommended by the World Health Organization (WHO), to quantify the distributive inequalities in the burden of diseases associated with high BMI. These rates were reported per 100 000 population as crude incidence rates, death rates, and DALYs rates. All the estimates were generated with a 95% uncertainty interval (UIs).ResultsGlobally, we revealed that an estimated age-standardised mortality rate associated with high BMI is 6.26 million (95% UIs = 3.99, 8.91). The age-standardised DALYs rate is 19.32 million (95% UIs = 12.77, 26.40), and the global population attributable fraction was 9% (95% UIs = 5, 12) in 2019. The largest number of high-BMI-related deaths in women mainly concentrated in the age group of 65-79 years, whereas the largest number in men was in the age group of 60-69 years. The age-standardised DALYs rate of diseases associated with high BMI was larger in the high-middle and middle socio-demographic index (SDI) (population attributable fraction (PAF) = 11 and PAF = 9) regions than those with high SDI (PAF = 1) and low SDI (PAF = 5) regions.ConclusionsIn this study, our results showed that the disease burden of global deaths and DALYs associated with high BMI has substantially increased between 1990-2019. Furthermore, we demonstrated that countries with higher SDI development levels shoulders higher burden of diseases associated with high BMI. Future policies to prevent and reduce the burden should be developed and implemented based on country-specific development status.

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The burden of antimicrobial resistance in the Americas in 2019: a cross-country systematic analysis

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