Editor's Note: Tuberculosis (TB) remains a significant public health challenge worldwide, particularly in economically underdeveloped regions. Although progress has been made in TB diagnosis and treatment in recent years, factors such as the emergence of drug-resistant strains, the prevalence of HIV, and high TB incidence rates among impoverished populations continue to threaten TB control efforts. A recent study on disease burden published in The Lancet Infectious Diseases examines global, regional, and national TB mortality and incidence rates, as well as the TB burden across different age groups. This study provides a comprehensive assessment of current TB control progress and offers crucial insights for future prevention and control strategies.
Despite being a preventable and largely treatable disease, tuberculosis continues to be a major contributor to the global burden of disease. Each year, TB causes over one million deaths, making it the leading cause of death from an infectious source in 2019. In response to this challenge, global TB control initiatives have gained prominence since the early 1990s, achieving certain milestones.
The World Health Organization’s (WHO) End TB Strategy aims to accelerate TB control efforts through global cooperation. The strategy’s goals include reducing TB deaths by 95% and TB incidence by 90% between 2015 and 2035, with the ultimate aim of ensuring no families face catastrophic financial burdens due to TB by 2035.
The year 2020 was a critical juncture for evaluating progress towards TB elimination, with targets to reduce TB deaths by 35% and TB incidence by 20%. However, the WHO’s 2022 Global Tuberculosis Report reveals that between 2015 and 2021, TB deaths decreased by only 5.9% and incidence by 10%, falling short of the 2020 targets. Moreover, the study did not adequately consider age-specific differences.
The study indicates that although the TB burden among children remains high, older populations generally experience the highest TB mortality and incidence rates. Diagnostic challenges specific to certain age groups, age-specific disease patterns, immunosenescence, and other age-related immune dysfunctions, along with comorbidities common in elderly patients, may mask TB symptoms. Therefore, evaluating progress towards the End TB Strategy milestones by age group, while assessing the role of key risk factors, can inform targeted interventions and accelerate TB elimination.
This study aims to evaluate the burden and trends of TB and its risk factors across five different age groups at global, regional, and national levels from 1990 to 2021, and to report the progress of each age group from 2015 to 2020.
Using the Global Burden of Disease Study 2021 (GBD 2021) analytical framework, the study estimated TB mortality and incidence rates for different age groups across 204 countries and regions from 1990 to 2021.
The study quantified TB mortality among HIV-negative populations using data from 22,603 site-years of vital registration data, 1,718 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) diagnostic data. These estimates were input into the cause-of-death ensemble modeling platform. The population attributable fraction method was used to determine HIV and TB deaths for specific age groups.
All available population-based data sources, including prevalence surveys, annual case notifications, tuberculin surveys, and TB mortality, were analyzed in DisMod-MR 2.1 to derive internally consistent age-specific estimates of TB incidence, prevalence, and mortality. The study also estimated age-specific TB mortality among HIV-negative populations attributable to three risk factors: smoking, alcohol consumption, and diabetes, both independently and collectively.
As a secondary analysis, the study compared the expected TB deaths, modeled from 2015 to 2019 vital registration data, with observed TB deaths in 2020 and 2021 from countries with cause-specific mortality data, to investigate the potential impact of the COVID-19 pandemic on TB mortality among HIV-negative populations.
Global Overview of TB Incidence and Mortality
In 2021, an estimated 9.4 million new TB cases occurred globally, with about 1 million co-infected with HIV. Among the 1.35 million TB deaths, approximately 205,000 involved HIV co-infection. In 2021, the age-standardized incidence rate of all forms of TB was 115 per 100,000 population, and the age-standardized mortality rate was 16.2 per 100,000 population. From 1990 to 2021, the global age-standardized TB incidence rate decreased by 37.0%, and the global age-standardized TB mortality rate decreased by 61.1%.
Age-Specific TB Burden
Assessments of global changes in TB incidence revealed that children under 5 and the 5–14 age group experienced the most significant changes, with reductions of 4.1% and 3.7% respectively between 2010 and 2021, compared to approximately 2% reductions in adult age groups over the same period. Similarly, in terms of TB mortality, the under-5 and 5–14 age groups saw the most significant decreases, with declines of 7.9% and 6.6% respectively between 2010 and 2021, compared to 4.0%–4.7% decreases in adult age groups during the same period.
Progress Towards the 2020 Milestone of the End TB Strategy
From 2015 to 2020, the global all-age TB incidence rate decreased by 6.26%. Among 204 countries, 15 achieved a 20% reduction in all-age TB incidence, with 8 countries located in West Sub-Saharan Africa. By age stratification, TB incidence rates decreased by 16.5%, 16.2%, 6.29%, 5.72%, and 8.48% among the under-5, 5–14, 15–49, 50–69, and 70 and older age groups, respectively.
From 2015 to 2020, the global number of TB deaths decreased by 11.9%. Seventeen countries achieved the target of a 35% reduction in TB deaths, with most located in Eastern Europe (6 countries) and Central Europe (4 countries). The greatest reductions in TB deaths were observed among children under 5 (35.3%) and children aged 5–14 (29.5%), while the smallest reduction was observed among the elderly aged 70 and older (3.29%).
After removing the combined impact of the three TB risk factors (smoking, alcohol consumption, and diabetes), the global TB death toll in 2020 would decrease from 1.39 million to 1 million, representing a 36.5% reduction compared to the TB death toll observed in 2015. Among different age groups, TB mortality rates declined by 31.0% among the 15–49 age group, 40.5% among the 50–69 age group, and 41.0% among the elderly aged 70 and older.
Impact of the COVID-19 Pandemic on TB Mortality
In assessing the impact of the COVID-19 pandemic on TB deaths among HIV-negative populations, the research team analyzed data from 41 countries for 2020 and 20 countries for 2021. In 2020, the expected number of TB deaths across all age groups was 50,900 (95% CI: 49,700–52,400), while the observed number was 45,500, resulting in 5,340 fewer deaths (95% CI: 4070–6920). In 2021, the expected number of TB deaths across all age groups was 39,600 (95% CI: 38,300–41,100), while the observed number was 39,000, resulting in 657 fewer deaths (95% CI: -713–2180).
Despite accelerated global progress in reducing the TB burden over the past decade, the world failed to meet the first mid-term milestone target of the WHO’s End TB Strategy by 2020. The pace of progress varied significantly across age groups, with the elderly population aged 50 and older showing the slowest progress in reducing TB burden. To address this challenge, countries should consider adapting and refining their national TB control programs by drawing on the experiences of those countries that have successfully achieved the 2020 milestone targets. Additionally, targeted interventions should be considered to improve TB control outcomes among the elderly population.
