Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019.

Background: 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.

Methods: 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.

Findings: 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.

Interpretation: 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.

Funding: Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care, using UK aid funding managed by the Fleming Fund.

Competing Interests: Declaration of interests S Afzal reports support for the present manuscript from Department of Community Medicine and Epidemiology, King Edward Medical University; participation on a data and safety monitoring board or advisory board with Corona Expert Advisory Group and Dengue Expert Advisory Group; leadership or fiduciary roles in board, society, committee, or advocacy groups, unpaid with Pakistan Society of Community Medicine & Public Health, Pakistan Association of Medical Editors, and Pakistan Society of Medical Infectious Diseases. S Bhaskar reports support for the present manuscript from leadership or fiduciary roles in board, society, committee or advocacy groups, paid or unpaid with the Rotary Club of Sydney and Global Health and Migration Hub Community, Global Health Hub Germany as a Board Director and Co-Manager. X Dai reports support for the present manuscript from the Institute for Health Metrics and Evaluation (IHME) and University of Washington. S Das reports grants or contracts from The Department of Science & Technology (DST) Grant of 16 Lakh INR by the Government of India for COVID-19 Research; leadership or fiduciary roles in board, society, committee or advocacy groups, paid or unpaid with Program Chair The American Association for Clinical Chemistry (AACC) India Section as an executive member in Ambi, India. S J Dunachie reports support for the present manuscript from UK National Institute of Health and Care Research (NIHR), funded by an NIHR Global Research Professorship (NIHR300791); grants or contracts from UK Research and Innovation (UKRI; MR/W02067X/1 and MR/W020653/1), Wellcome Drug Resistant Infections Discretionary Award, UK Department of Health and Social Care, and US Defense Threat Reduction Agency; and consulting fees from the Scottish Parliament and funding committees for Wellcome. C Herteliu reports grants or contracts from Romanian Ministry of Research Innovation and Digitalization, MCID and Romanian National Authority for Scientific Research and Innovation, and CNDS-UEFISCDI. N E Ismail reports leadership or fiduciary roles in board, society, committee, or advocacy groups, unpaid with Malaysian Academy of Pharmacy as a Council Member. J J Jozwiak reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Teva, Amgen, Synexus, Boehringer Ingelheim, ALAB Laboratories, and Zentiva. N J Kassebaum reports research support for the GBD Study and the present manuscript from The Bill & Melinda Gates Foundation. F Krapp Lopez reports support for the present manuscript from University of Oxford, and financial support provided to Universidad Peruana Cayetano Heredia for data extraction and preparation for the present manuscript. K Krishan reports other non-financial support from UGC Centre of Advanced Study, CAS II, Department of Anthropology, Panjab University, Chandigarh, India. A-F A Mentis reports grants or contracts from MilkSafe (A novel pipeline to enrich formula milk using omics technologies), a research co-financed by the European Regional Development Fund of the EU and Greek national funds through the Operational Program Competitiveness, Entrepreneurship and Innovation, under the call RESEARCH - CREATE - INNOVATE (project code: T2EDK-02222), as well as from ELIDEK (Hellenic Foundation for Research and Innovation, MIMS-860); stocks in a family winery; other financial or non-financial support from the BGI group as a scientific officer. N Milevska Kostova reports grants or contracts from BD Europe and Pfizer (institutional grant for patient education); payment or honoraria for lectures or educational events from Pfizer; and support for attending meetings or travel from Pfizer. S Mohammed reports support for the present manuscript from The Bill & Melinda Gates Foundation and grants or contracts from Alexander von Humboldt Foundation. L Monasta reports support for the present manuscript from the Italian Ministry of Health on project Ricerca Corrente (34/2017) and payments made to the Institute for Maternal and Child Health IRCCS Burlo Garofolo. C E Moore reports support for the present manuscript from the UK Department of Health and Social Care, Wellcome Trust, and The Bill & Melinda Gates Foundation. S B Munro reports stock or stock options in Invitae as an employee. V C F Pepito reports grants from Sanofi Consumer Healthcare and International Initiative for Impact Evaluation. M J Postma reports leadership or fiduciary roles in board, society, committee, or advocacy groups, paid or unpaid, with the Joint Committee of Vaccination and Immunization as a member and stock or stock options in PAG BV (Groningen, Netherlands) and HealthEcore (Zeist, Netherlands). A Radfar reports other support from Avicenna Medical and Clinical Research Institute. K E Rudd reports support for the present manuscript from the National Institutes of Health, National Institute of General Medical Sciences (grant K23GM141463), and consulting fees from Janssen Pharmaceuticals. B Sartorius reports grants or contracts from the Fleming Fund; leadership or fiduciary roles in board, society, committee, or advocacy groups, paid or unpaid, with WHO Reference Group on Health Statistics and GBD Scientific Council. S Shrestha reports other financial or non-financial support from the Graduate Research Merit Scholarship from the School of Pharmacy, Monash University Malaysia. L M L R Silva reports grants or contracts from project code CENTRO-04-3559-FSE-000162, Fundo Social Europeu (FSE). J A Singh reports consulting fees from Crealta/Horizon, Medisys, Fidia, PK Med, Two Labs, Adept Field Solutions, Clinical Care options, Clearview healthcare partners, Putnam associates, Focus forward, Navigant consulting, Spherix, MedIQ, Jupiter Life Science, UBM, Trio Health, Medscape, WebMD, Practice Point communications, the National Institutes of Health, and the American College of Rheumatology; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Simply Speaking; support for attending meetings or travel from the steering committee of OMERACT; participation on a data safety monitoring board or advisory board with the US Food and Drug Administration Arthritis Advisory Committee; leadership or fiduciary role in board, society, committee or advocacy group, paid or unpaid, with OMERACT as a steering committee member, as Chair of the Veterans Affairs Rheumatology Field Advisory Committee, and as Editor and Director of the UAB Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis; stock or stock options in TPT Global Tech, Vaxart Pharmaceuticals, Atyu Biopharma, Adaptimmune Therapeutics, GeoVax Labs, Pieris Pharmaceuticals, Enzolytics, Seres Therapeutics, Tonix Pharmaceuticals, and Charlotte's Web Holdings; and previously owning stock options in Amarin, Viking, and Moderna pharmaceuticals. E Upadhyay reports patents published: “A system and method of reusable filters for anti-pollution mask” (patent application number 202011003559), and “A system and method for electricity generation through crop stubble by using microbial fuel cells” (patent application number 202011008531), patents filed: “A system for disposed personal protection equipment (PPE) into biofuel through pyrolysis and method” (patent application number 202111005659) and “A novel herbal pharmaceutical aid for formulation of gel and method thereof” (patent application number 202111023335); and leadership or fiduciary roles in board, society, committee, or advocacy groups, paid or unpaid, with the Indian Meteorological Society, Jaipur Chapter (India) as a joint secretary and life member. H R van Doorn reports participation on a data and safety monitoring board or advisory board with Wellcome SEDRIC (Surveillance and Epidemiology of Drug Resistant Infections).

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