Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019.
Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019.
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DOI：
10.1016/s0140-6736(22)02185-7
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发表时间：
2022-12-17
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减少感染造成的死亡负担是一项紧迫的全球公共卫生优先事项。先前的研究估计了与耐药感染和败血症相关的死亡人数，发现感染仍然是全球死亡的主要原因。了解常见细菌病原体（包括对抗菌剂敏感和耐药）的全球负担对于确定对公共卫生的最大威胁至关重要。据我们所知，这是第一项对11种主要感染综合征中33种细菌病原体相关死亡进行全球综合估计的研究。我们使用2019年全球疾病负担、伤害和风险因素研究（GBD）的方法，以及2019年全球抗菌素耐药性负担研究中描述的输入数据子集，估计了2019年11种感染性综合征中与33种细菌属或种相关的死亡。该研究包括3.43亿个个体记录或分离株，覆盖11361个研究地点年。我们使用了三个建模步骤来估计与每种病原体相关的死亡人数：感染起作用的死亡人数，归因于给定传染性综合征的感染死亡人数比例，以及归因于给定病原体的传染性综合征死亡人数比例。2019年，我们为204个国家和地区的所有年龄段以及男性和女性提供了估计。按照标准GBD方法，通过对每个目标量进行1000次后验抽取，取第2·5和第97·5次采样，计算与33种细菌病原体相关的死亡和感染最终估计值的95%不确定性区间（UI）。在2019年估计的1370万（95% UI 10.9 - 17.1）感染相关死亡中，在本研究估计的11种感染综合征中，有770万（5.7 - 10.2）与33种细菌病原体（对抗菌药物耐药和敏感）相关。我们估计与33种细菌病原体相关的死亡占2019年全球所有死亡的13.6%（10.2 - 18.1）和所有脓毒症相关死亡的56.2%（52.1 - 60.1）。五种主要病原体-金黄色葡萄球菌、大肠杆菌、肺炎链球菌、肺炎克雷伯菌和铜绿假单胞菌-在所调查的细菌中造成54.9%（52.9 - 56.9）的死亡。最致命的传染性综合征和病原体因地点和年龄而异。与这些细菌病原体相关的年龄标准化死亡率在撒哈拉以南非洲超级区域最高，每10万人口中有230例死亡（185-285），在高收入超级区域最低，每10万人口中有52.2例死亡（37.4 - 71.5）。在135个国家，金黄色葡萄球菌是导致死亡的主要细菌原因，在全球范围内，金黄色葡萄球菌也与15岁以上人群的大多数死亡有关。在5岁以下的儿童中，肺炎链球菌是与大多数死亡相关的病原体。2019年，三种细菌感染综合征导致600多万人死亡，其中下呼吸道感染和血液感染各导致200多万人死亡，腹膜和腹腔内感染导致100多万人死亡。我们在这项研究中调查的33种细菌病原体是全球健康损失的重要来源，它们在感染性综合征和地点之间的分布存在相当大的差异。与GBD 3级潜在死亡原因相比，与这些细菌相关的死亡将成为2019年全球第二大死亡原因;因此，它们应被视为全球卫生界干预的紧急优先事项。解决细菌感染负担的战略包括预防感染、优化抗生素的使用、提高微生物分析能力、疫苗开发以及改进和更普遍地使用现有疫苗。这些估计可用于帮助确定疫苗需求、需求和开发的优先次序。比尔和梅林达盖茨基金会，惠康信托基金会，卫生和社会保健部，使用由弗莱明基金管理的英国援助资金。
Reducing the burden of death due to infection is an urgent global public health priority. Previous studies have estimated the number of deaths associated with drug-resistant infections and sepsis and found that infections remain a leading cause of death globally. Understanding the global burden of common bacterial pathogens (both susceptible and resistant to antimicrobials) is essential to identify the greatest threats to public health. To our knowledge, this is the first study to present global comprehensive estimates of deaths associated with 33 bacterial pathogens across 11 major infectious syndromes. We estimated deaths associated with 33 bacterial genera or species across 11 infectious syndromes in 2019 using methods from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, in addition to a subset of the input data described in the Global Burden of Antimicrobial Resistance 2019 study. This study included 343 million individual records or isolates covering 11 361 study-location-years. We used three modelling steps to estimate the number of deaths associated with each pathogen: deaths in which infection had a role, the fraction of deaths due to infection that are attributable to a given infectious syndrome, and the fraction of deaths due to an infectious syndrome that are attributable to a given pathogen. Estimates were produced for all ages and for males and females across 204 countries and territories in 2019. 95% uncertainty intervals (UIs) were calculated for final estimates of deaths and infections associated with the 33 bacterial pathogens following standard GBD methods by taking the 2·5th and 97·5th percentiles across 1000 posterior draws for each quantity of interest. From an estimated 13·7 million (95% UI 10·9–17·1) infection-related deaths in 2019, there were 7·7 million deaths (5·7–10·2) associated with the 33 bacterial pathogens (both resistant and susceptible to antimicrobials) across the 11 infectious syndromes estimated in this study. We estimated deaths associated with the 33 bacterial pathogens to comprise 13·6% (10·2–18·1) of all global deaths and 56·2% (52·1–60·1) of all sepsis-related deaths in 2019. Five leading pathogens—Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa—were responsible for 54·9% (52·9–56·9) of deaths among the investigated bacteria. The deadliest infectious syndromes and pathogens varied by location and age. The age-standardised mortality rate associated with these bacterial pathogens was highest in the sub-Saharan Africa super-region, with 230 deaths (185–285) per 100 000 population, and lowest in the high-income super-region, with 52·2 deaths (37·4–71·5) per 100 000 population. S aureus was the leading bacterial cause of death in 135 countries and was also associated with the most deaths in individuals older than 15 years, globally. Among children younger than 5 years, S pneumoniae was the pathogen associated with the most deaths. In 2019, more than 6 million deaths occurred as a result of three bacterial infectious syndromes, with lower respiratory infections and bloodstream infections each causing more than 2 million deaths and peritoneal and intra-abdominal infections causing more than 1 million deaths. The 33 bacterial pathogens that we investigated in this study are a substantial source of health loss globally, with considerable variation in their distribution across infectious syndromes and locations. Compared with GBD Level 3 underlying causes of death, deaths associated with these bacteria would rank as the second leading cause of death globally in 2019; hence, they should be considered an urgent priority for intervention within the global health community. Strategies to address the burden of bacterial infections include infection prevention, optimised use of antibiotics, improved capacity for microbiological analysis, vaccine development, and improved and more pervasive use of available vaccines. These estimates can be used to help set priorities for vaccine need, demand, and development. Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care, using UK aid funding managed by the Fleming Fund.