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: Enteric infectious diseases claim more than 1 million lives annually and are among the top ten causes of death in children younger than 5 years. Remarkable global investment has been dedicated to enteric infectious disease prevention and control; however, the shifting global health landscape is testing the continuance of progress. To evaluate the current status and guide future interventions, we present the latest epidemiological estimates of enteric infectious diseases from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 and assess progress towards the Global Action Plan for the Prevention and Control of Pneumonia and Diarrhoea (GAPPD) mortality target of fewer than 20 deaths per 100 000 children younger than 5 years by 2025. Methods: We quantified the incidence, mortality, and disability-adjusted life-years (DALYs) of enteric infectious diseases by age, sex, and year across 204 countries and territories from 1990 to 2023. In GBD 2023, the following were considered under the category of enteric infectious diseases: diarrhoeal diseases, enteric fever (typhoid and paratyphoid), invasive non-typhoidal Salmonella spp (iNTS) infections, and other intestinal infectious diseases. We also examined 15 aetiologies contributing to diarrhoeal diseases. Incidence and prevalence were estimated with DisMod-MR (version 2.1), a Bayesian meta-regression tool, drawing on data from systematic reviews, population-based surveys, claims data, and hospital sources. Cause-specific mortality was modelled with Cause of Death Ensemble Modelling based on data from sources including vital registration, mortality surveillance, verbal autopsy, and minimally invasive tissue sampling. Years of life lost and years lived with disability were computed and combined to derive DALYs. For aetiology-specific estimation, population-attributable fractions (PAFs) for 15 pathogens were derived with a counterfactual framework. Point estimates and 95% uncertainty intervals (UIs) were generated from 250 draws from the posterior distribution. Findings: In 2023, enteric infectious diseases resulted in an estimated 1·27 million (95% UI 0·963–1·68) deaths globally, declining from 3·69 million (3·04–4·56) in 1990. The global age-standardised mortality rate (ASMR) decreased from 74·1 (62·0–92·9) per 100 000 population to 16·4 (12·6–21·3) per 100 000 population during the same period. Diarrhoeal diseases accounted for most deaths in 2023 (1·11 million [0·811–1·54]), followed by enteric fever and iNTS. South Asia and sub-Saharan Africa remained the most affected regions in 2023, with 599 000 (441 000–882 000) and 501 000 (373 000–648 000) deaths due to enteric infectious diseases, respectively, predominantly from diarrhoeal disease. Rotavirus was the leading cause of all-age diarrhoeal disease deaths (PAF 16·3% [12·0–21·5]), followed by norovirus (10·2% [2·4–17·0]) and Shigella spp (9·3% [5·4–15·2]). Among children younger than 5 years, PAFs of deaths due to diarrhoeal diseases were 40·2% (32·5–48·5) for rotavirus, 24·0% (15·1–36·7) for Shigella spp, and 23·4% (13·7–34·3) for adenovirus. Across 204 countries and territories, 141 met the GAPPD mortality target in 2023. The driving aetiologies among countries that did not meet the target in 2023 varied slightly by GBD super-region, but the highest or second-highest number of deaths in children younger than 5 years were consistently attributed to rotavirus. Astrovirus and sapovirus, newly included in GBD 2023, were responsible for 24 600 (6290–49 000) and 18 800 (4650–44 400) deaths, respectively, in 2023, mainly in children younger than 5 years. Interpretation: Our findings show that mortality and ASMRs of enteric infectious diseases declined substantially between 1990 and 2023. This decline is consistent with the expansion of public health measures and broader socioeconomic development. However, the burden in 2023 remains considerably high, with the highest mortality concentrated in sub-Saharan Africa and south Asia. Considering that more than a quarter of all countries had yet to meet the GAPPD mortality target in 2023, sustained efforts are needed to address the persistent burden in affected countries and to adapt to the changing global health landscape. Funding: Gates Foundation.
Background: Since its inception in 1974, the Essential Programme on Immunization (EPI) has achieved remarkable success, averting the deaths of an estimated 154 million children worldwide through routine childhood vaccination. However, more recent decades have seen persistent coverage inequities and stagnating progress, which have been further amplified by the COVID-19 pandemic. In 2019, WHO set ambitious goals for improving vaccine coverage globally through the Immunization Agenda 2030 (IA2030). Now halfway through the decade, understanding past and recent coverage trends can help inform and reorient strategies for approaching these aims in the next 5 years. Methods: Based on the Global Burden of Diseases, Injuries, and Risk Factors Study 2023, this study provides updated global, regional, and national estimates of routine childhood vaccine coverage from 1980 to 2023 for 204 countries and territories for 11 vaccine-dose combinations recommended by WHO for all children globally. Employing advanced modelling techniques, this analysis accounts for data biases and heterogeneity and integrates new methodologies to model vaccine scale-up and COVID-19 pandemic-related disruptions. To contextualise historic coverage trends and gains still needed to achieve the IA2030 coverage targets, we supplement these results with several secondary analyses: (1) we assess the effect of the COVID-19 pandemic on vaccine coverage; (2) we forecast coverage of select life-course vaccines up to 2030; and (3) we analyse progress needed to reduce the number of zero-dose children by half between 2023 and 2030. Findings: Overall, global coverage for the original EPI vaccines against diphtheria, tetanus, and pertussis (first dose [DTP1] and third dose [DTP3]), measles (MCV1), polio (Pol3), and tuberculosis (BCG) nearly doubled from 1980 to 2023. However, this long-term trend masks recent challenges. Coverage gains slowed between 2010 and 2019 in many countries and territories, including declines in 21 of 36 high-income countries and territories for at least one of these vaccine doses (excluding BCG, which has been removed from routine immunisation schedules in some countries and territories). The COVID-19 pandemic exacerbated these challenges, with global rates for these vaccines declining sharply since 2020, and still not returning to pre-COVID-19 pandemic levels as of 2023. Coverage for newer vaccines developed and introduced in more recent years, such as immunisations against pneumococcal disease (PCV3) and rotavirus (complete series; RotaC) and a second dose of the measles vaccine (MCV2), saw continued increases globally during the COVID-19 pandemic due to ongoing introductions and scale-ups, but at slower rates than expected in the absence of the pandemic. Forecasts to 2030 for DTP3, PCV3, and MCV2 suggest that only DTP3 would reach the IA2030 target of 90% global coverage, and only under an optimistic scenario. The number of zero-dose children, proxied as children younger than 1 year who do not receive DTP1, decreased by 74·9% (95% uncertainty interval 72·1–77·3) globally between 1980 and 2019, with most of those declines reached during the 1980s and the 2000s. After 2019, counts of zero-dose children rose to a COVID 19-era peak of 18·6 million (17·6–20·0) in 2021. Most zero-dose children remain concentrated in conflict-affected regions and those with various constraints on resources available to put towards vaccination services, particularly sub-Saharan Africa. As of 2023, more than 50% of the 15·7 million (14·6–17·0) global zero-dose children resided in just eight countries (Nigeria, India, Democratic Republic of the Congo, Ethiopia, Somalia, Sudan, Indonesia, and Brazil), emphasising persistent inequities. Interpretation: Our estimates of current vaccine coverage and forecasts to 2030 suggest that achieving IA2030 targets, such as halving zero-dose children compared with 2019 levels and reaching 90% global coverage for life-course vaccines DTP3, PCV3, and MCV2, will require accelerated progress. Substantial increases in coverage are necessary in many countries and territories, with those in sub-Saharan Africa and south Asia facing the greatest challenges. Recent declines will need to be reversed to restore previous coverage levels in Latin America and the Caribbean, especially for DTP1, DTP3, and Pol3. These findings underscore the crucial need for targeted, equitable immunisation strategies. Strengthening primary health-care systems, addressing vaccine misinformation and hesitancy, and adapting to local contexts are essential to advancing coverage. COVID-19 pandemic recovery efforts, such as WHO's Big Catch-Up, as well as efforts to bolster routine services must prioritise reaching marginalised populations and target subnational geographies to regain lost ground and achieve global immunisation goals. Funding: The Bill & Melinda Gates Foundation and Gavi, the Vaccine Alliance.
Background: Tuberculosis (TB) is the leading global cause of death from a single infectious agent. Recent reductions in global health funding have threatened TB control, making comprehensive assessment of TB, HIV-related TB, and drug-resistant TB burdens before these disruptions essential for shaping effective responses. The WHO End TB Strategy sets targets of a 95% reduction in TB deaths and a 90% reduction in TB incidence between 2015 and 2035. Using results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, this study aims to assess the burden of TB and multidrug-resistant TB (MDR-TB) across 204 countries and territories, and to evaluate progress towards the WHO End TB incidence and mortality targets. Methods: We quantified TB mortality using the Cause of Death Ensemble modelling platform with global vital registration, surveillance, verbal autopsy, and minimally invasive tissue sampling data. For TB morbidity estimation, we simultaneously modelled incidence, prevalence, and mortality by age and sex using DisMod-MR 2.1. A population attributable fraction (PAF) approach was applied to stratify morbidity and mortality estimates by HIV and drug-resistance status. We also calculated disability-adjusted life-years (DALYs) as the sum of years of life lost and years lived with disability. For the risk factor analysis, a comparative risk assessment framework was used and PAFs were derived for alcohol use, smoking, and high fasting plasma glucose to determine the proportion of TB burden associated with these risk factors. Findings: In 2023, there were an estimated 9·11 million (95% uncertainty interval 8·04–10·3) incident cases of all-form TB, 1·22 million (0·98–1·49) deaths, and 54·6 million (43·8–65·5) DALYs globally. HIV-related TB comprised 781 000 (690 000–879 000) incident cases and 210 000 (142 000–279 000) deaths, contributing 11·0 million (7·56–14·3) DALYs. MDR-TB accounted for 466 000 (198 000–1 080 000) incident cases, 102 000 (31 700–238 000) deaths, and 3·96 million (1·31–9·01) DALYs. From 2015 to 2023, global all-form TB incidence rates declined by 19·2% (17·8–20·5) and deaths declined by 22·6% (4·7–35·7); declines were larger for drug-susceptible TB than for MDR-TB. Sub-Saharan Africa and south Asia had the highest mortality burdens in 2023; reductions in all-form TB incidence and mortality were uneven between 2000 and 2023, with limited progress in both measures in Latin America and the Caribbean. Removing smoking, alcohol use, and high fasting plasma glucose would reduce global TB deaths to 768 000 (592 000–970 000) and DALYs to 34·9 million (27·8–43·8) in 2023; MDR-TB deaths would decrease to 77 200 (23 400–183 000) and DALYs to 3·12 million (1·03–7·29). Interpretation: Global progress towards WHO End TB targets is disparate and fragile. Although many regions achieved meaningful gains, others have stagnated in recent years. The complexity of TB prevention is amplified by divergent MDR-TB trends, the persistent burden of HIV, and growing exposure to modifiable risk factors. Recent volatility in global health financing threatens to further destabilise this vulnerable epidemiological landscape; concerted action is urgently needed to temper disruptions and preserve progress. Funding: Gates Foundation.