Background: Lower respiratory infections (LRIs) remain the world's leading infectious cause of death. This analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides global, regional, and national estimates of LRI incidence, mortality, and disability-adjusted life-years (DALYs), with attribution to 26 pathogens, including 11 newly modelled pathogens, across 204 countries and territories from 1990 to 2023. With new data and revised modelling techniques, these estimates serve as an update and expansion to GBD 2021. Through these estimates, we also aimed to assess progress towards the 2025 Global Action Plan for the Prevention and Control of Pneumonia and Diarrhoea (GAPPD) target for pneumonia mortality in children younger than 5 years. Methods: Mortality from LRIs, defined as physician-diagnosed pneumonia or bronchiolitis, was estimated using the Cause of Death Ensemble model with data from vital registration, verbal autopsy, surveillance, and minimally invasive tissue sampling. The Bayesian meta-regression tool DisMod-MR 2.1 was used to model overall morbidity due to LRIs. DALYs were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs) for all locations, years, age groups, and sexes. We modelled pathogen-specific case-fatality ratios (CFRs) for each age group and location using splined binomial regression to create internally consistent estimates of incidence and mortality proportions attributable to viral, fungal, parasitic, and bacterial pathogens. Progress was assessed towards the GAPPD target of less than three deaths from pneumonia per 1000 livebirths, which is roughly equivalent to a mortality rate of less than 60 deaths per 100 000 children younger than 5 years. Findings: In 2023, LRIs were responsible for 2·50 million (95% uncertainty interval [UI] 2·24–2·81) deaths and 98·7 million (87·7–112) DALYs, with children younger than 5 years and adults aged 70 years and older carrying the highest burden. LRI mortality in children younger than 5 years fell by 33·4% (10·4–47·4) since 2010, with a global mortality rate of 94·8 (75·6–116·4) per 100 000 person-years in 2023. Among adults aged 70 years and older, the burden remained substantial with only marginal declines since 2010. A mortality rate of less than 60 deaths per 100 000 for children younger than 5 years was met by 129 of the 204 modelled countries in 2023. At a super-regional level, sub-Saharan Africa had an aggregate mortality rate in children younger than 5 years (hereafter referred to as under-5 mortality rate) furthest from the GAPPD target. Streptococcus pneumoniae continued to account for the largest number of LRI deaths globally (634 000 [95% UI 565 000–721 000] deaths or 25·3% [24·5–26·1] of all LRI deaths), followed by Staphylococcus aureus (271 000 [243 000–298 000] deaths or 10·9% [10·3–11·3]), and Klebsiella pneumoniae (228 000 [204 000–261 000] deaths or 9·1% [8·8–9·5]). Among pathogens newly modelled in this study, non-tuberculous mycobacteria (responsible for 177 000 [95% UI 155 000–201 000] deaths) and Aspergillus spp (responsible for 67 800 [59 900–75 900] deaths) emerged as important contributors. Altogether, the 11 newly modelled pathogens accounted for approximately 22% of LRI deaths. Interpretation: This comprehensive analysis underscores both the gains achieved through vaccination and the challenges that remain in controlling the LRI burden globally. Furthermore, it demonstrates persistent disparities in disease burden, with the highest mortality rates concentrated in countries in sub-Saharan Africa. Globally, as well as in these high-burden locations, the under-5 LRI mortality rate remains well above the GAPPD target. Progress towards this target requires equitable access to vaccines and preventive therapies—including newer interventions such as respiratory syncytial virus monoclonal antibodies—and health systems capable of early diagnosis and treatment. Expanding surveillance of emerging pathogens, strengthening adult immunisation programmes, and combating vaccine hesitancy are also crucial. As the global population ages, the dual challenge of sustaining gains in child survival while addressing the rising vulnerability in older adults will shape future pneumonia control strategies. Funding: Gates Foundation.

Background: The global burden of sepsis, a life-threatening dysregulated host response to infection leading to organ dysfunction, remains challenging to quantify. We aimed to comprehensively estimate the global, regional, and national burden of sepsis, including the impact of the COVID-19 pandemic and underlying causes of sepsis-related deaths with co-occurring infectious syndromes. Methods: We used multiple cause-of-death, hospital, minimally invasive tissue sampling, and linked death certificate and hospital record data representing 149 million deaths, covering 4290 location-years with mortality estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 to capture explicit and implicit sepsis cases and deaths. We estimated age-location-sex-specific fractions of sepsis-related deaths from 195 underlying causes of death and 22 infectious syndromes from 1990 to 2021 using binomial logistic regression models, and estimated sepsis-related deaths using GBD cause-specific mortality estimates. Using 250 million hospital admissions and 7·82 million deaths from hospital data, representing 1310 location-years, we modelled case fatality rates by use of binomial logistic regression, applied to sepsis death estimates to estimate sepsis incidence by age, location, and year. Findings: In 2021, we estimated 166 million (95% uncertainty interval 135–201) sepsis cases and 21·4 million (20·3–22·5) all-cause sepsis-related deaths globally, representing 31·5% of total global deaths. Sepsis-related deaths decreased between 1990 and 2019, followed by a surge in 2020 and 2021. As of 2021, individuals aged 15 years and older experienced increases across incidence (230%) and mortality (26·3%) since 1990. Those aged 70 years and older had the highest sepsis-related mortality in 2021 (9·28 million [8·74–9·86] deaths). Sepsis-related deaths from infectious underlying causes decreased from 11·8 million (11·1–12·5) in 1990 to 8·34 million (7·72–9·01) in 2019, then increased by 86·4% to 15·5 million (14·7–16·4) in 2021. Sepsis-related mortality due to non-infectious underlying causes of death increased from 4·69 million (4·35–5·05) in 1990 to 5·81 million (5·40–6·25) in 2021; the leading non-infectious underlying causes of death with sepsis were stroke, chronic obstructive pulmonary disease, and cirrhosis. In 2021, bloodstream infections inclusive of HIV and malaria (3·08 million [2·83–3·35]) and lower respiratory infections inclusive of COVID-19 (11·33 million [1·20–1·47]) were the most prominent infectious syndromes complicating sepsis-related deaths from non-infectious underlying causes, representing a consistent trend since 1990. Interpretation: The global burden of sepsis increased in 2020 and 2021, reversing progress from 1990. Sepsis incidence and mortality increased in people aged 15 years and older, especially those aged 70 years and older, and as a complication of non-infectious underlying causes of death such as stroke, primarily through bloodstream infections and lower respiratory infections. The global burden of sepsis is substantial, and sepsis is increasingly a complication of non-infectious causes of death. Funding: Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.

Background: Meningitis remains the leading infectious cause of neurological disabilities globally, disproportionately affecting children younger than 5 years and populations in the African meningitis belt. Whereas previous global estimates focused on ten pathogen categories, this study presents the most comprehensive analysis to date, assessing the meningitis burden attributable to 17 causative pathogens based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 framework. Methods: GBD is a systematic, scientific effort aimed at quantifying the comparative magnitude of health loss caused by diseases, injuries, and risk factors across age groups, sexes, and geographical locations over time. We estimated meningitis mortality using the Cause of Death Ensemble model (CODEm) and morbidity using DisMod-MR 2.1, incorporating data from vital registration, verbal autopsy, surveillance, hospital data, and systematic reviews. Aetiology-specific estimates were generated with pathogen-linked case-fatality ratios and splined binomial regression models. Risk factor attribution was based on established risk–outcome pairs and population attributable fractions. Findings: In 2023, there were 259 000 (95% uncertainty interval 202 000–335 000) global deaths and 2·54 million (2·20–2·93) incident cases of meningitis. Children younger than 5 years accounted for more than a third of deaths (86 600 [53 300–149 000]). Streptococcus pneumoniae, Neisseria meningitidis, non-polio enteroviruses, and other viruses were the leading causes of death, while non-polio enteroviruses caused the most cases. The four WHO-defined preventable meningitis pathogens of interest (S pneumoniae, N meningitidis, Haemophilus influenzae, and Group B streptococcus) contributed to 98 700 deaths (77 000–127 000) and 594 000 cases (514 000–686 000). Low birthweight, short gestation, and household air pollution were the top risk factors for meningitis-related mortality. Interpretation: Although mortality and incidence have declined significantly since 1990, progress is insufficient to meet WHO 2030 targets. Despite marked progress in reducing bacterial meningitis via global vaccination campaigns, a substantial meningitis burden persists, attributable both to common pathogens such as S pneumoniae and N meningitidis and to emerging non-bacterial pathogens such as Candida spp and drug-resistant fungi. Achieving WHO goals will require sustained investment in surveillance, vaccination, maternal screening, and health-system strengthening, especially in high-burden settings. Funding: Gates Foundation, Wellcome Trust, and UK Department of Health and Social Care.