Vincent Mougin

BACKGROUND: A 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. METHODS: We 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. FINDINGS: In 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. INTERPRETATION: This 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. FUNDING: Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.

BACKGROUND: Despite a global epidemiological transition towards increased burden of non-communicable diseases, communicable diseases continue to cause substantial morbidity and mortality worldwide. Understanding the burden of a wide range of infectious diseases, and its variation by geography and age, is pivotal to research priority setting and resource mobilisation globally. METHODS: We estimated disability-adjusted life-years (DALYs) associated with 85 pathogens in 2019, globally, regionally, and for 204 countries and territories. The term pathogen included causative agents, pathogen groups, infectious conditions, and aggregate categories. We applied a novel methodological approach to account for underlying, immediate, and intermediate causes of death, which counted every death for which a pathogen had a role in the pathway to death. We refer to this measure as the burden associated with infection, which was estimated by combining different sources of information. To compare the burden among all pathogens, we used pathogen-specific ratios to incorporate the burden of immediate and intermediate causes of death for pathogens modelled previously by the GBD. We created the ratios by using multiple cause of death data, hospital discharge data, linkage data, and minimally invasive tissue sampling data to estimate the fraction of deaths coming from the pathway to death chain. We multiplied the pathogen-specific ratios by age-specific years of life lost (YLLs), calculated with GBD 2019 methods, and then added the adjusted YLLs to age-specific years lived with disability (YLDs) from GBD 2019 to produce adjusted DALYs to account for deaths in the chain. We used standard GBD methods to calculate 95% uncertainty intervals (UIs) for final estimates of DALYs by taking the 2·5th and 97·5th percentiles across 1000 posterior draws for each quantity of interest. We provided burden estimates pertaining to all ages and specifically to the under 5 years age group. FINDINGS: Globally in 2019, an estimated 704 million (95% UI 610-820) DALYs were associated with 85 different pathogens, including 309 million (250-377; 43·9% of the burden) in children younger than 5 years. This burden accounted for 27·7% (and 65·5% in those younger than 5 years) of the previously reported total DALYs from all causes in 2019. Comparing super-regions, considerable differences were observed in the estimated pathogen-associated burdens in relation to DALYs from all causes, with the highest burden observed in sub-Saharan Africa (314 million [270-368] DALYs; 61·5% of total regional burden) and the lowest in the high-income super-region (31·8 million [25·4-40·1] DALYs; 9·8%). Three leading pathogens were responsible for more than 50 million DALYs each in 2019: tuberculosis (65·1 million [59·0-71·2]), malaria (53·6 million [27·0-91·3]), and HIV or AIDS (52·1 million [46·6-60·9]). Malaria was the leading pathogen for DALYs in children younger than 5 years (37·2 million [17·8-64·2]). We also observed substantial burden associated with previously less recognised pathogens, including Staphylococcus aureus and specific Gram-negative bacterial species (ie, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, and Helicobacter pylori). Conversely, some pathogens had a burden that was smaller than anticipated. INTERPRETATION: Our detailed breakdown of DALYs associated with a comprehensive list of pathogens on a global, regional, and country level has revealed the magnitude of the problem and helps to indicate where research funding mismatch might exist. Given the disproportionate impact of infection on low-income and middle-income countries, an essential next step is for countries and relevant stakeholders to address these gaps by making targeted investments. FUNDING: Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.

BACKGROUND: Gout is an inflammatory arthritis manifesting as acute episodes of severe joint pain and swelling, which can progress to chronic tophaceous or chronic erosive gout, or both. Here, we present the most up-to-date global, regional, and national estimates for prevalence and years lived with disability (YLDs) due to gout by sex, age, and location from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, as well as forecasted prevalence to 2050. METHODS: Gout prevalence and YLDs from 1990 to 2020 were estimated by drawing on population-based data from 35 countries and claims data from the USA and Taiwan (province of China). Nested Bayesian meta-regression models were used to estimate prevalence and YLDs due to gout by age, sex, and location. Prevalence was forecast to 2050 with a mixed-effects model. FINDINGS: In 2020, 55·8 million (95% uncertainty interval 44·4-69·8) people globally had gout, with an age-standardised prevalence of 659·3 (525·4-822·3) per 100 000, an increase of 22·5% (20·9-24·2) since 1990. Globally, the prevalence of gout in 2020 was 3·26 (3·11-3·39) times higher in males than in females and increased with age. The total number of prevalent cases of gout is estimated to reach 95·8 million (81·1-116) in 2050, with population growth being the largest contributor to this increase and only a very small contribution from the forecasted change in gout prevalence. Age-standardised gout prevalence in 2050 is forecast to be 667 (531-830) per 100 000 population. The global age-standardised YLD rate of gout was 20·5 (14·4-28·2) per 100 000 population in 2020. High BMI accounted for 34·3% (27·7-40·6) of YLDs due to gout and kidney dysfunction accounted for 11·8% (9·3-14·2). INTERPRETATION: Our forecasting model estimates that the number of individuals with gout will increase by more than 70% from 2020 to 2050, primarily due to population growth and ageing. With the association between gout disability and high BMI, dietary and lifestyle modifications focusing on bodyweight reduction are needed at the population level to reduce the burden of gout along with access to interventions to prevent and control flares. Despite the rigour of the standardised GBD methodology and modelling, in many countries, particularly low-income and middle-income countries, estimates are based on modelled rather than primary data and are also lacking severity and disability estimates. We strongly encourage the collection of these data to be included in future GBD iterations. FUNDING: Bill & Melinda Gates Foundation and the Global Alliance for Musculoskeletal Health.

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

Une étude de la métallurgie antique du fer a été engagée au Pays Basque, dans la vallée de Baigorri, un secteur dont les gisements métallifères ont été exploités dès avant l’Antiquité et parfois jusqu’au XXe siècle. Les prospections et les investigations entreprises ont révélé l’existence de deux districts miniers et métallurgiques dont la chronologie est comprise entre la fin de l’âge du Fer (IIe siècle a.C.) et le IVe siècle p.C. Les mines, les charbonnières et les sites métallurgiques des deux centres de production ont été identifiés, tandis que quatre ateliers de réduction ont fait l’objet d’une étude archéologique particulière. Ces résultats ont été confrontés aux données paléoenvironnementales issues de l’analyse palynologique et géochimique d’une tourbière de la haute vallée de Baigorri.