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Data showing 7.7 million deaths from 33 bacterial infections can guide measures to strengthen health systems, particularly in low-income settings

Common bacterial infections were linked to one in eight global deaths in 2019—and represented the second leading cause of death that year, according to findings published in the Lancet by the Global Research on Antimicrobial Resistance (GRAM) Project. The Project is hosted by the Centre for Tropical Medicine and Global Health, at the Nuffield Department of Medicine.

There were 7.7 million deaths in 2019 associated with 33 common bacterial infections, with five bacteria alone connected to half of these mortalities, according to the research by GRAM, a partnership between the Institute for Health Metrics and Evaluation (IHME) and the University of Oxford. The deadliest bacterial pathogens and types of infection varied by location and age.

Second only to ischaemic heart disease as the leading cause of death, the analysis highlights reducing bacterial infections as a global public health priority. Building stronger health systems with greater diagnostic laboratory capacity, implementing control measures, and optimising antibiotic use are crucial to lessen the burden of disease caused by common bacterial infections, researchers said.

“These new data for the first time reveal the full extent of the global public health challenge posed by bacterial infections,” said Dr. Christopher Murray, study co-author and Director of the Institute for Health Metrics and Evaluation (IHME) at the University of Washington’s School of Medicine. “It is of utmost importance to put these results on the radar of global health initiatives so that a deeper dive into these deadly pathogens can be conducted and proper investments are made to slash the number of deaths and infections.”

GRAM is supported by the UK Fleming Fund, the Wellcome Trust, and the Bill and Melinda Gates Foundation to estimate the global burden of antimicrobial resistance (AMR). The study follows findings from earlier this year, which estimated that bacterial AMR caused more than 1.2 million deaths in 2019, and called for further interventions, including infection prevention and control. Read the study, ‘Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis’, in the Lancet.

While many estimates exist for pathogens such as tuberculosis, malaria, and HIV, until now estimates of the disease burden of bacterial pathogens as a whole were limited to specific populations or infection types. More deaths were linked to two of the deadliest pathogens – S. aureus and E. coli – than HIV/AIDS (864,000 deaths) in 2019, yet analysis shows HIV research was awarded $42 billion dollars while E. coli research was awarded $800 million. The authors say such funding gaps might have arisen because there was, until now, a lack of data on the global burden of these infections.

The new study provides the first global estimates of mortality associated with 33 common bacterial pathogens and 11 major infection types – known as infectious syndromes – leading to death from sepsis. Estimates were produced for all ages and sexes across 204 countries and territories. Utilising data and methods from the Global Burden of Disease 2019 and Global Research on Antimicrobial Resistance (GRAM) studies [1], the authors used 343 million individual records and pathogen isolates to estimate deaths associated with each pathogen and the type of infection responsible.

World map showing the mortality rate per 100,000 population for 33 bacteria in 2019

Of the estimated 13.7 million infection-related deaths that occurred in 2019, 7.7 million were associated with the 33 bacterial pathogens studied. Deaths associated with these bacteria accounted for 13.6% of all global deaths, and more than half of all sepsis-related deaths, in 2019. More than 75% of the 7.7 million bacterial deaths occurred because of three syndromes: lower respiratory infections (LRI), bloodstream infections (BSI), and peritoneal and intra-abdominal infections (IAA).

Five pathogens – S. aureusE. coliS. pneumoniaeK. pneumoniae, and P. aeruginosa – were responsible for 54.2% of deaths among the bacteria studied. The pathogen associated with the most deaths globally was S. aureus, with 1.1 million deaths. Four other pathogens were each associated with more than 500,000 deaths: E. coli (950 000 deaths), S. pneumoniae (829,000), K. pneumonia (790,000), and Pseudomonas aeruginosa (559,000). A similar number of female and male deaths were associated with the leading bacterial pathogens.

Age-standardised mortality rates varied by location, as did the deadliest pathogens. Sub-Saharan Africa recorded the highest mortality rate, with 230 deaths per 100,000 population. By comparison, the high-income super-region – which includes countries in Western Europe, North America and Australasia – recorded the lowest mortality rate, with 52 deaths per 100,000 population. S. aureus was the leading bacterial cause of death in 135 countries, followed by E. coli (37 countries), S. pneumoniae (24 countries), and K. pneumoniae and Acinetobacter baumannii (4 countries each). Country-level data is available in Appendix Table S2.

“Prior to this study there has been a lack of country-level estimates in many of the poorest and under-resourced parts of the world where people are worst affected by bacterial infections,” said Dr Benn Sartorius, one of the lead researchers for the GRAM study at University of Oxford. “The data and estimates generated by this important study could help guide targeted prevention efforts in low- and middle-income countries, disproportionally affected with the highest burden of bacterial infections, and help save lives and reduce years of life lost due to bacterial infection.”

Prof Christiane Dolecek, also a lead researcher for the GRAM study at the University of Oxford, said: “This study will be useful for the development of targeted strategies to reduce the high bacterial disease burden in the worst affected countries, by improving access to and availability of basic acute health care services and strengthening infection prevention and control measures, as well as expanding vaccine coverage for bacterial pathogens. This evidence should serve as a call to arms for global vaccine developers to enhance and expedite the development and implementation of new vaccines for priority bacterial pathogens for which a vaccine is not currently available.”

The pathogens associated with the most deaths differed by age. With 940,000 deaths, S. aureus was associated with the most deaths in adults aged over 15 years. The most deaths in children aged 5 to 14 years were associated with Salmonella enterica serovar Typhi, with 49,000 deaths. In children older than newborns but under 5 years of age, S. pneumoniae was the deadliest pathogen, accounting for 225,000 deaths. The pathogen associated with the most neonatal deaths was K. pneumoniae, with 124,000 deaths.

The authors acknowledge some limitations to their study, many of which are due to a lack of data. Limited data is available for some parts of the world, particularly many low- and middle-income countries (LMICs), where the estimated burden of disease is greatest. This underscores the need to improve data collection capacity and surveillance systems in LMICs. Combining and standardising data from a wide variety of sources also introduces potential sources of bias, including misclassification of community- or hospital-acquired infections as well as data from passive surveillance systems that may overestimate the virulence or drug-resistance of pathogens.

[1] GBD 2019: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30925-9/fulltext; GRAM: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02724-0/fulltext

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