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

Abstract

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 center dot 40 million (95% uncertainty interval [UI] 8 center dot 36 to 10 center dot 5) tuberculosis incident cases and 1 center dot 35 million (1 center dot 23 to 1 center dot 52) deaths due to tuberculosis in 2021. At the global level, the all-age tuberculosis incidence rate declined by 6 center dot 26% (5 center dot 27 to 7 center dot 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 center dot 5% (14 center dot 8 to 18 center dot 4) in children younger than 5 years, 16 center dot 2% (14 center dot 2 to 17 center dot 9) in those aged 5-14 years, 6 center dot 29% (5 center dot 05 to 7 center dot 70) in those aged 15-49 years, 5 center dot 72% (4 center dot 02 to 7 center dot 39) in those aged 50-69 years, and 8 center dot 48% (6 center dot 74 to 10 center dot 4) in those aged 70 years and older, from 2015 to 2020. Global tuberculosis deaths decreased by 11 center dot 9% (5 center dot 77 to 17 center dot 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 center dot 3% (26 center dot 7 to 41 center dot 7) decrease in tuberculosis deaths in children younger than 5 years, a 29 center dot 5% (25 center dot 5 to 34 center dot 1) decrease in those aged 5-14 years, a 15 center dot 2% (10 center dot 0 to 20 center dot 2) decrease in those aged 15-49 years, a 7 center dot 97% (0 center dot 472 to 14 center dot 1) decrease in those aged 50-69 years, and a 3 center dot 29% (-5 center dot 56 to 9 center dot 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 center dot 39 million (1 center dot 28 to 1 center dot 54) to 1 center dot 00 million (0 center dot 703 to 1 center dot 23) in 2020, representing a 36 center dot 5% (21 center dot 5 to 54 center dot 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.