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Global, regional, and national age-specific progress towards the 2020 milestones of the WHO End TB Strategy: a systematic analysis for the Global Burden of Disease Study 2021
Background
Global evaluations of the progress towards the WHO End TB Strategy 2020 interim milestones on mortality (35% reduction) and incidence (20% reduction) have not been age specific. We aimed to assess global, regional, and national-level burdens of and trends in tuberculosis and its risk factors across five separate age groups, from 1990 to 2021, and to report on age-specific progress between 2015 and 2020.
Methods
We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021) analytical framework to compute age-specific tuberculosis mortality and incidence estimates for 204 countries and territories (1990–2021 inclusive). We quantified tuberculosis mortality among individuals without HIV co-infection using 22 603 site-years of vital registration data, 1718 site-years of verbal autopsy data, 825 site-years of sample-based vital registration data, 680 site-years of mortality surveillance data, and 9 site-years of minimally invasive tissue sample (MITS) diagnoses data as inputs into the Cause of Death Ensemble modelling platform. Age-specific HIV and tuberculosis deaths were established with a population attributable fraction approach. We analysed all available population-based data sources, including prevalence surveys, annual case notifications, tuberculin surveys, and tuberculosis mortality, in DisMod-MR 2.1 to produce internally consistent age-specific estimates of tuberculosis incidence, prevalence, and mortality. We also estimated age-specific tuberculosis mortality without HIV co-infection that is attributable to the independent and combined effects of three risk factors (smoking, alcohol use, and diabetes). As a secondary analysis, we examined the potential impact of the COVID-19 pandemic on tuberculosis mortality without HIV co-infection by comparing expected tuberculosis deaths, modelled with trends in tuberculosis deaths from 2015 to 2019 in vital registration data, with observed tuberculosis deaths in 2020 and 2021 for countries with available cause-specific mortality data.
Findings
We estimated 9·40 million (95% uncertainty interval [UI] 8·36 to 10·5) tuberculosis incident cases and 1·35 million (1·23 to 1·52) deaths due to tuberculosis in 2021. At the global level, the all-age tuberculosis incidence rate declined by 6·26% (5·27 to 7·25) between 2015 and 2020 (the WHO End TB strategy evaluation period). 15 of 204 countries achieved a 20% decrease in all-age tuberculosis incidence between 2015 and 2020, eight of which were in western sub-Saharan Africa. When stratified by age, global tuberculosis incidence rates decreased by 16·5% (14·8 to 18·4) in children younger than 5 years, 16·2% (14·2 to 17·9) in those aged 5–14 years, 6·29% (5·05 to 7·70) in those aged 15–49 years, 5·72% (4·02 to 7·39) in those aged 50–69 years, and 8·48% (6·74 to 10·4) in those aged 70 years and older, from 2015 to 2020. Global tuberculosis deaths decreased by 11·9% (5·77 to 17·0) from 2015 to 2020. 17 countries attained a 35% reduction in deaths due to tuberculosis between 2015 and 2020, most of which were in eastern Europe (six countries) and central Europe (four countries). There was variable progress by age: a 35·3% (26·7 to 41·7) decrease in tuberculosis deaths in children younger than 5 years, a 29·5% (25·5 to 34·1) decrease in those aged 5–14 years, a 15·2% (10·0 to 20·2) decrease in those aged 15–49 years, a 7·97% (0·472 to 14·1) decrease in those aged 50–69 years, and a 3·29% (–5·56 to 9·07) decrease in those aged 70 years and older. Removing the combined effects of the three attributable risk factors would have reduced the number of all-age tuberculosis deaths from 1·39 million (1·28 to 1·54) to 1·00 million (0·703 to 1·23) in 2020, representing a 36·5% (21·5 to 54·8) reduction in tuberculosis deaths compared to those observed in 2015. 41 countries were included in our analysis of the impact of the COVID-19 pandemic on tuberculosis deaths without HIV co-infection in 2020, and 20 countries were included in the analysis for 2021. In 2020, 50 900 (95% CI 49 700 to 52 400) deaths were expected across all ages, compared to an observed 45 500 deaths, corresponding to 5340 (4070 to 6920) fewer deaths; in 2021, 39 600 (38 300 to 41 100) deaths were expected across all ages compared to an observed 39 000 deaths, corresponding to 657 (–713 to 2180) fewer deaths.
Interpretation
Despite accelerated progress in reducing the global burden of tuberculosis in the past decade, the world did not attain the first interim milestones of the WHO End TB Strategy in 2020. The pace of decline has been unequal with respect to age, with older adults (ie, those aged >50 years) having the slowest progress. As countries refine their national tuberculosis programmes and recalibrate for achieving the 2035 targets, they could consider learning from the strategies of countries that achieved the 2020 milestones, as well as consider targeted interventions to improve outcomes in older age groups
Breeding Progress and Future Challenges: Biotic Stresses
Mungbean is a short-duration legume crop cultivated in South Asia, Southeast Asia and Australasia. Its cultivation is rapidly spreading to other parts of the world. Insect pests and diseases are the major constraints in increasing the productivity of mungbean crop. The important diseases in mungbean include mungbean yellow mosaic, anthracnose, powdery mildew, Cercospora leaf spot, dry root rot, halo blight, bacterial leaf spot and tan spot. The major insect-pests of mungbean are stem fly, thrips, aphids, whitefly, pod borers and bruchids. Development of host plant resistance to insect pests and diseases in mungbean by breeding for resistance is an alternative, economical and environment-friendly approach. Though breeding for resistance to insect pests and diseases has been extensively studied in mungbean, the success rate in stabilizing the resistance has been less due to the development of insect biotypes, new strains in pathogens and the environmental interactions. This chapter covers the insect and disease resistance sources in mungbean, resistant traits, the genetic basis of resistance and different breeding methods involved in breeding for insect and disease resistance
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
Age-sex differences in the global burden of lower respiratory infections and risk factors, 1990-2019: results from the Global Burden of Disease Study 2019
Background The global burden of lower respiratory infections (LRIs) and corresponding risk factors in children older than 5 years and adults has not been studied as comprehensively as it has been in children younger than 5 years. We assessed the burden and trends of LRIs and risk factors across a groups by sex, for 204 countries and territories.Methods In this analysis of data for the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we used dinician-diagnosed pneumonia or bronchiolitis as our case definition for LRIs. We included International Classification of Diseases 9th edition codes 079.6, 466-469, 470.0, 480-482.8, 483.0-483.9, 484.1-484.2, 484.6-484.7, and 487-489 and International Classification of Diseases 10th edition codes A48.1, A70, B97.4 B97.6, 109-115.8, J16 J16.9, J20-121.9, J91.0, P23.0 P23.4, and U04 U04.9. We used the Cause of Death Ensemble modelling strategy to analyse 23109 site-years of vital r *stration data, 825 site-years of sample vital registration data, 1766 site-years of verbal autopsy data, and 681 site-years of mortality surveillance data. We used DisMod-MR 2.1, a Bayesian metaregression tool, to analyse age sex-specific incidence and prevalence data identified via systematic reviews of the literature, population-based survey data, and daims and inpatient data. Additio y, we estimated age sex-specific LRI mortality that is attributable to the independent effects of 14 risk factors.Findings Globally, in 2019, we estimated that there were 257 million (95% uncertainty interval [UI] 240-275) LRI incident episodes in males and 232 million (217-248) in females. In the same year, LRIs accounted for 1.30 million (95% UI 1.18-1.42) male deaths and 1.20 million (1.07-1.33) female deaths. Age-standardised incidence and mortality rates were 1.17 times (95% UI 1.16-1.18) and 1.31 times (95% UI 1.23-1.41) greater in males than in fe es in 2019. Between 1990 and 2019, LRI incidence and mortality rates declined at different rates across age groups and an increase in LRI episodes and deaths was estimated among all adult age groups, with males aged 70 years and older having the highest increase in LRI episodes (126.0% [95% UI 121.4-131.1]) and deaths (100.0% [83.4-115.9]). During the same period, LRI episodes and deaths in children younger than 15 years were estimated to have decreased, and the greatest dedine was observed for LRI deaths in males younger than 5 years (-70.7% [-77.2 to 61.8]). The leading risk factors for LRI mortality varied across age groups and sex. More than half of global LRI deaths in children younger than 5 years were attributable to child wasting (population attributable fraction [PAF] 53.0% [95% UI 37.7-61.8] in males and 56.4% [40.7-65.1] in females), and more than a quarter of LRI deaths among those aged 5-14 years were attributable to household air pollution (PAF 26.0% [95% UI 16.6-35.5] for males and PAF 25.8% [16.3-35.4] for females). PAFs of male LRI deaths attributed to smoking were 20.4% (95% UI 15.4-25.2) in those aged 15-49 years, 305% (24.1-36. 9) in those aged 50-69 years, and 21.9% (16. 8-27. 3) in those aged 70 years and older. PAFs of female LRI deaths attributed to household air pollution were 21.1% (95% UI 14.5-27.9) in those aged 15-49 years and 18 " 2% (12.5-24.5) in those aged 50-69 years. For females aged 70 years and older, the leading risk factor, ambient particulate matter, was responsible for 11-7% (95% UI 8.2-15.8) of LRI deaths.Interpretation The patterns and progress in reducing the burden of LRIs and key risk factors for mortality varied across age groups and sexes. The progress seen in children you - than 5 years was dearly a result of targeted interventions, such as vaccination and reduction of exposure to risk factors. Similar interventions for other age groups could contribute to the achievement of multiple Sustainable Development Goals targets, induding promoting wellbeing at all ages and reducing health inequalities. Interventions, including addressing risk factors such as child wasting, smoking, ambient particulate matter pollution, and household air pollution, would prevent deaths and reduce health disparities.Copyright 2022 The Author(s). Published by Elsevier Ltd