Global Burden of Tuberculosis in Adults Aged 65 Years and Older, 1990–2021: A Population-Based Study

Global Burden of Tuberculosis in Adults Aged 65 Years and Older, 1990–2021: A Population-Based Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Global Burden of Tuberculosis in Adults Aged 65 Years and Older, 1990–2021: A Population-Based Study Yushu Liu, Canyou Zhang, Tao Li, Mingkuan Fan, Yuhong Li, Hui Chen, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7602192/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background To estimate the burden, trends, and inequalities of tuberculosis (TB) among older adults at the global, regional, and national levels from 1990 to 2021. Methods We analyzed the global burden of tuberculosis in adults aged ≥ 65 years using data from the GBD Study 2021 across 204 countries from 1990 to 2021. Disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) were assessed, with uncertainty quantified by 95% CIs . Countries were grouped by region and sociodemographic index (SDI). Descriptive statistics, age-standardized rates (ASRs), and average annual percentage changes (AAPCs) were computed to evaluate TB burden variations by age, sex, and location. Changes in factors affecting DALYs for tuberculosis in older adults were also analyzed. Results Between 1990 and 2021, the proportion of tuberculosis-related DALYs among older adults increased from 12.45% to 18.38% of the total population. In 2021, an estimated 8.63 million individuals aged 65 years and older (95% UI 7.75 to 9.74) were affected by TB-related DALYs, with an age-standardized rate of 1,122 per 100,000 population. Although the age-standardized DALY rate for older adults steadily declined from 1990 to 2021, the annual reduction was slower than that of the overall population (-3.26% per year [95% UI -3.38% to -3.15%]). While YLLs decreased, the proportion of YLDs rose from 6.5% to 10.2% of total DALYs during the same period. Men consistently showed higher DALY counts and rates than women across all age groups in 2021. Globally, TB-related DALYs decreased across sociodemographic strata, with the largest declines in high SDI countries (-4.98% [95% UI -5.19% to -4.78%]) and the slowest in low SDI countries (-2.73% [95% UI -2.85% to -2.62%]). In 2021, Central and Eastern Sub-Saharan Africa (9,899 and 8,439 per 100,000, respectively) had the highest DALY rates, whereas high-income regions had the lowest. High fasting plasma glucose, tobacco use, and alcohol consumption were key contributors to TB DALYs, with only fasting plasma glucose rising between 1990 and 2021. Conclusions The tuberculosis burden among older adults has significantly increased, with disparities observed across countries with varying sociodemographic indices, accounting for nearly one-fifth of the global TB burden by 2021. Managing high fasting plasma glucose levels remains a major challenge for older adults. Targeted guidelines are urgently needed to address these specific health needs. Figures Figure 1 Figure 2 Figure 3 Introduction Three decades after the World Health Organization (WHO) declared tuberculosis (TB) a global public health emergency, the disease remains the second leading cause of death from a single infectious agent, following coronavirus disease (COVID-19) in 2022. TB was responsible for nearly double the number of deaths compared to HIV/AIDS. In 2022, over 10 million people fell ill with TB, and 1.3 million people died from the disease[ 1 ]. To combat TB, the WHO launched the End TB Strategy[ 2 ], aiming for a 90% reduction in TB incidence and a 95% reduction in TB-related deaths by 2035. Despite substantial progress in TB control over the past two decades, current trends indicate that meeting these targets remains a significant challenge. The pace of decline has been uneven, with older adults experiencing the slowest reduction in TB burden[ 3 ]. Greater focus and integrated strategies are required, particularly for vulnerable groups, including the elderly[ 4 ]. The impact of an aging population on TB epidemiology demands significant attention. By 2050, the global population of older adults is expected to reach 2.1 billion, accounting for 22% of the total population[ 5 ]. Due to immune decline, physiological changes, malnutrition, and numerous other factors, older adults are more susceptible to various diseases, increasing their risk of tuberculosis[ 6 ]. In this population, TB is often linked to the reactivation of latent infections[ 7 ]. The WHO estimates that one-third of the global population is infected with TB, placing older adults at a heightened risk of developing active disease.\ The elderly population experiences a higher risk of morbidity and mortality than other populations due to the high rate of latent tuberculosis infection, coupled with factors such as declining immune function, insufficient care, and a high prevalence of underlying diseases[ 8 ], making them a priority population for tuberculosis control. However, the global burden of TB among older adults, measured in disability-adjusted life years (DALYs), remains underexplored. To achieve End TB targets, the impact of population aging on TB epidemiology and strategy must be considered. TB causes lifelong disability, a factor not captured by cross-sectional prevalence. DALYs offer a comprehensive measure by accounting for years lost to ill health, disability, or premature death. Drawing on data from the Global Burden of Disease (GBD) 2021 study, we analyzed the global, regional, and national burden of TB among older adults. Our analysis focused on DALYs, years of life lost (YLLs), and years lived with disability (YLDs) from 1990 to 2021, while also investigating key factors contributing to the DALY burden in older TB patients. Methods Study population and data collection The global burden of TB in older adults (aged ≥ 65 years) was analyzed using data from the Global Burden of Disease (GBD) Study 2021. This comprehensive dataset includes 369 diseases and 87 risk factors across 204 countries and territories, providing a robust foundation for analysis. Data were sourced from the Global Health Data Exchange and include repeated cross-sectional data spanning 1990 to 2021. We extracted information on TB, including location, age, and sex-specific DALYs, YLLs, YLDs, alongside DALYs attributable to individual risk factors, all accompanied by 95% uncertainty intervals (UIs). Countries and territories were categorized into 21 regions based on epidemiological and geographical similarities and further categorized into five sociodemographic index (SDI) levels: low, low-middle, middle, high-middle, and high SDI. The SDI, a composite measure, is derived from lag-distributed income per capita, the total fertility rate among females under 25, and the average years of schooling in adults aged ≥ 15 years. Data were stratified by seven age groups (65–69, 70–74, 75–79, 80–84, 85–89, 90–94, and ≥ 95 years) and analyzed for both sexes. Special attention was given to the 30 high TB burden countries, including Angola, Bangladesh, Brazil, Central African Republic, China, Congo, Democratic People's Republic of Korea, Democratic Republic of the Congo, Ethiopia, Gabon, India, Indonesia, Kenya, Lesotho, Liberia, Mongolia, Mozambique, Myanmar, Namibia, Nigeria, Pakistan, Papua New Guinea, Philippines, Sierra Leone, South Africa, Thailand, Uganda, United Republic of Tanzania, Viet Nam, and Zambia, as well as the three countries on the global TB watchlist: Cambodia, the Russian Federation, and Zimbabwe. Statistical analyses A descriptive analysis was conducted to characterize the global TB burden among adults aged 65 years and older. The burden was quantified by calculating DALYs, YLLs, YLDs, age-standardized rates (ASRs) with corresponding 95% uncertainty intervals (UIs), and average annual percentage changes (AAPCs) with 95% confidence intervals (CIs). These metrics were computed to assess the disease burden attributable to risk factors across different age groups, sexes, years, and locations. All estimates incorporated uncertainty, accounting for variability in primary data sources, model assumptions, measurement errors, and data handling processes. This uncertainty was quantified statistically and reflected in the 95% UIs for each location and estimate. The UIs were derived from 1,000 draw-levels sampled from the posterior distribution of models, with the 95% UIs defined as the range between the 2.5th and 97.5th percentiles. ASRs, calculated using direct standardization, applied age-specific rates to a standard age distribution to compare the burden of disease across populations with different age structures. This standardization helped eliminate the effects of age differences in the population, providing a clearer understanding of the true variations in disease burden. AAPCs captured the average annual rate of change over the study period, indicating whether the burden was increasing, decreasing, or stable. A rate was considered to be trending upward or downward if the annual percentage change and its 95% CI were both positive or negative, respectively. AAPCs were calculated using the standard formula. All analyses were conducted in R software (R Core Team, version 4.4.1, Vienna, Austria). $$\:\begin{array}{c}Age\:standardised\:rate=\frac{{\sum\:}_{i=1}^{A}{a}_{i}{w}_{i}}{{\sum\:}_{i=1}^{A}{w}_{i}}\#\left(1\right)\end{array}$$ where \(\:{a}_{i}\) is the age-specific death rate and \(\:{w}_{i}\) is the weight in the same age subgroup of the chosen reference standard population (in which \(\:i\) denotes the \(\:{i}^{th}\) age class) and A is the upper age limit. $$\:\begin{array}{c}AAPC=\left\{\text{exp}\left(\frac{\sum\:{w}_{i}{b}_{i}}{{w}_{i}}\right)-1\right\}\times\:100\#\left(2\right)\end{array}$$ \(\:{b}_{i}\) is the slope coefficient for the \(\:{i}^{th}\) segment, with \(\:i\) indexing the segments in the desired range of years, and \(\:{w}_{i}\) is the length of each segment in the range of years. Patient and public involvement The Global Burden of Disease Study represents a collaborative scientific initiative, enabling comparative analysis of the impact of various health conditions across age, sex, and geographic regions at specific points in time. This work has garnered significant attention in the scientific, policy, and public spheres worldwide. Our study utilized secondary data from this collaborative effort, and we did not have direct access to individual participants. No patients were involved in formulating the research question, defining the outcome measures, or contributing to the design and execution of the study. Results Global trends Globally, in 2021, an estimated 8.63 million (95% UI 7.75–9.74) people aged 65 years and older experienced DALYs due to TB. The age-standardized DALY rate was 1,122 per 100,000 population (Table 1 ). The proportion of DALYs due to tuberculosis among older people has shown an upward trend relative to the overall number of DALYs in the entire population, increasing from 12.45% in 1990 to 18.38% in 2021 (Fig. 1 ). The number of DALYs in the 65 + population gradually increased to a peak of 11.09 million before 1998, then declined significantly after 2000 and remained virtually unchanged after 2015. In contrast, the number of DALYs in the total population declined consistently from 1990 to 2021 (see supplementary Fig. 1). Furthermore, the age-standardized DALY rate for tuberculosis in the elderly has consistently been higher than that of the total population, and its rate of decline has been slower (see supplementary Fig. 2). The age-standardized DALY rate of TB among this age group decreased by 64%, from 3,122 per 100,000 population in 1990 to 1,122 per 100,000 population in 2021, with an average annual trend of -3.26% (Table 1 ). Furthermore, YLLs and YLDs varied inversely. The number of YLLs for tuberculosis in people over 65 years of age decreased while the number of YLDs increased from 0.67 million to 0.88 million (see supplementary Fig. 3). Notably, the proportion of YLDs in DALYs increased from 6.5% to 10.2% (see supplementary Fig. 4). The age-standardized DALY rate for the population aged 65 and above increased from 1.89 times that of the overall population in 1990 to 1.93 times in 2021 (see supplementary Fig. 5). Table 1 Age-standardized DALY and AAPC of tuberculosis in people aged ≥ 65 years at the global and regional level, 1990–2021. DALY (95% UI) AAPCs (%, 95% CI) No. of people with TB in 1990 (000s) ASR 1990(per 100,000) No. of people with TB in 2021 (000s) ASR 2021(per 100,000) Global 10295.23 (8650.21 to 11775.70) 3122.35 (2620.87 to 3573.96) 8633.87 (7754.21469 to 9740.3195) 1122 (1007.14 to 1265.66) -3.26 (-3.38 to -3.15) Sex Female 3891.55 (3410.38 to 4443.34) 2080.73(1820.33 to 2377.94) 3304.96 (2946.33 to 3704.08) 787.04(701.66 to 882.1) -3.1 (-3.18 to -3.01) Male 6403.68 (4950.23 to 7739.47) 4546.4(3503.06 to 5515.09) 5328.91 (4665.72 to 6396.93) 1532.45(1339.43 to 1840.16) -3.46 (-3.62 to -3.3) Age group (years) 65–69 3831.00 (3214.66 to 4342.91) 3099.28(2600.66 to 3513.41) 2902.57 (2615.92 to 3298.03) 1052.26(948.34 to 1195.62) -3.42 (-3.72 to -3.11) 70–74 3020.10 (2542.78 to 3458.11) 3567.28(3003.48 to 4084.65) 2368.52 (2124.03 to 2661.18) 1150.67(1031.89 to 1292.84) -3.61 (-3.89 to -3.33) 75–79 1925.98 (1629.26 to 2224.01) 3128.84(2646.82 to 3613.01) 1601.92 (1462.00 to 1792.15) 1214.64(1108.54 to 1358.88) -3.02 (-3.24 to -2.79) 80–84 1033.15 (864.77 to 1192.05) 2920.48(2444.53 to 3369.67) 1057.05 (945.87 to 1189.34) 1206.91(1079.97 to 1357.96) -2.8 (-3.17 to -2.43) 85–89 374.09 (309.89 to 429.83) 2475.6(2050.74 to 2844.47) 493.18 (430.93 to 558.23) 1078.65(942.5 to 1220.94) -2.69 (-3.07 to -2.3) 90–94 90.48 (72.95 to 104.53) 2111.39(1702.37 to 2439.33) 166.66 (140.38 to 191.13) 931.62(784.69 to 1068.38) -2.73 (-3.01 to -2.45) 95+ 20.44 (15.90 to 24.26) 2007.61(1562 to 2383.22) 43.97 (35.09 to 50.25) 806.71(643.79 to 922) -2.92 (-3.09 to -2.76) SDI High SDI 354.32 339.89 154.06 (129.71o 174.52) 70.61 -4.98 (-5.19 to -4.78) (322.55 to 383.47) (308.84 to 368.13) (59.89 to 80.03) High-middle SDI 711.62 848.6 370.74 (316.48 to 436.14) 201.88 -4.54 (-4.92 to -4.15) (598.31 to 833.02) (713.29 to 993.06) (172.36 to 237.42) Middle SDI 2798.30 3716.77 2278.90 (2011.63 to 2688.42) 1008.36 -4.13 (-4.21 to -4.06) (2338.52 to 3160.23) (3098.34 to 4205.43) (888.24 to 1189.06) Low-middle SDI 4193.87 9409.5 3727.99 (3277.99 to 4303.38) 3316.72 -3.33 (-3.54 to -3.11) (3474.33 to 4863.95) (7762.36 to 10947.08) (2908.32 to 3829.61) Low SDI 2231.67 13896.98 2097.49(1837.91 to 2465.45) (1837.91 to 2465.45) 5979.77 (5224.25 to 7007.73) -2.73 (-2.85 to -2.62) (1825.73 to 2693.92) (11340.42 to 16837.12) Note: Estimates are for individuals aged over 65 years. AAPCs = average annual percent changes. UI = uncertainty interval. CI = confidence interval. DALYs = disability-adjusted life years. SDI = Socio-Demographic Index. ASR = Age-standardized rate. Numbers in parentheses are 95% uncertainty intervals (cases and age-standardized rate) and 95% confidence intervals (AAPCs). Global trends by sex From 1990 to 2021, the age-standardized DALYs for TB among people aged ≥ 65 years decreased for both men and women worldwide (men: from 6.4 million to 5.3 million; women: from 3.9 million to 3.3 million). The decrease in TB DALYs was more rapid among men than women (AAPC − 3.46% vs. -3.10%). Notably, in all age subgroups, males had higher numbers and rates of DALYs than females (see supplementary Fig. 6). The sex ratio for DALYs due to tuberculosis was 1.65 in 1990 and decreased slightly to 1.61 by 2021 (Table 1 ). In 2021, the number of DALYs decreased with age for both males and females, with the highest number of DALYs in the 65–69 age group, amounting to 1.9 million for males and 1.0 million for females. The highest age-standardized DALY rates for both males and females occurred at ages 80–84 (1,620 vs. 902 per 100,000 population) (see supplementary Fig. 6). Global trends by age subgroup The age-standardized DALYs associated with TB among older people decreased across all age subgroups, with the most significant reductions observed among those aged 70–74 years (AAPC − 3.61%), followed by 65–69 years (− 3.42%) and 75–79 years (− 3.02%). Despite these declines, the 65–69 age group had the highest number of DALYs, reaching 2.9 million in 2021. The highest age-standardized rate (ASR) in 2021 was among those aged 75–79 years (1,215 per 100,000 population), followed closely by those aged 80–84 years (1,207 per 100,000 population). Notably, among all age subgroups, the number and rate of DALYs were higher for males than females (Table 1 , supplementary Fig. 6). In 2019 and 2021, the highest number of YLLs due to tuberculosis was in the 65–69 age group (3.61 million vs. 2.62 million). Meanwhile, the age-standardized DALY rate shifted from being highest in the 70–74 age group in 2019 (3,326 per 100,000) to the 80–84 age group in 2021 (1,091 per 100,000). From 1990 to 2021, the number of YLDs due to tuberculosis increased across all age groups. However, the age-standardized YLD rates declined, with the slowest declines observed in the 80–84 age group (− 1.76% per year) and the 65–69 age group (− 1.83% per year) (see supplementary table 1 ). Global trends by sociodemographic index From 1990 to 2021, age-standardized DALYs due to TB among older adults declined across all sociodemographic groups (Table 1 ). However, this reduction has been consistently slower in those aged ≥ 65 years compared to the general population, irrespective of sociodemographic level (Supplementary Fig. 7). While the decline in TB-related DALYs among older adults was observed across all sociodemographic strata, the steepest reduction occurred in countries with a high SDI (AAPC − 4.98%), more than twice the rate of decline seen in low SDI countries (AAPC − 2.73%) (Table 1 ). In 2021, DALY rates were highest in low SDI countries (5,980 per 100,000) and lowest in high SDI countries (71 per 100,000) (Table 1 ). With the exception of Southern Sub-Saharan Africa, where age-standardized DALY, YLL, and YLD rates initially rose before declining, all other regions exhibited a decline in these metrics as SDI increased (Supplementary Fig. 8). Globally, rising SDI was strongly associated with a marked decrease in age-standardized DALY rates. However, in countries like Somalia and the Central African Republic, age-standardized DALY, YLL, and YLD rates exceeded what would be expected based on SDI alone. Notably, Eritrea displayed a significantly higher-than-expected age-standardized YLD rate (Supplementary Fig. 9). Regional trends All 21 regions experienced a decline in TB-related DALYs among older adults between 1990 and 2021, at varying rates. East Asia saw the most pronounced reduction (AAPC − 6.14%), while Sub-Saharan Africa experienced the slowest decline (AAPC − 0.38%) (Supplementary Table 2, Supplementary Fig. 10). By 2021, the highest burden of TB DALYs among older adults was observed in Central Sub-Saharan Africa (9,899 per 100,000), Eastern Sub-Saharan Africa (8,439 per 100,000), and Western Sub-Saharan Africa (4,964 per 100,000). In contrast, the lowest DALY rates were recorded in high-income North America (17 per 100,000), Australasia (20 per 100,000), and Western Europe (35 per 100,000) (Supplementary Table 2). The geographical patterns of age-standardized YLL and YLD rates mirrored those of DALYs, with Central and Eastern Sub-Saharan Africa showing the highest values (Supplementary Table 2, Supplementary Fig. 10). National trends At the national level, TB DALYs are declining in most countries. The 30 high-burden and 3 global TB watchlist countries accounted for 86.31% of global DALYs in 2021. Among these 33 countries, India had the highest DALYs (3.10 million), YLLs (2.85 million), and YLDs (0.25 million), while the Central African Republic had the highest age-standardized DALY rate (22,785.55 per 100,000 people) (see Fig. 2 , Supplementary Table 3), YLL rate (21,677.08 per 100,000 people), and YLD rate (1,108.47 per 100,000 people) (see Supplementary Fig. 10, Supplementary Table 3). From 1990 to 2021, age-standardized DALY rates decreased in most countries. During this period, China had the fastest DALY decline (AAPC − 6.51%) among the 33 TB countries; however, only Zimbabwe (AAPC 1.35%/year) and Lesotho (AAPC 1.14%/year) showed increasing age-standardized DALY rate trends (see Fig. 3 , Supplementary Table 3). From 1990 to 2021, among the 30 high-burden TB countries, China had the fastest DALY decline (AAPC − 6.51%), while Zimbabwe had the highest increase in age-standardized TB DALYs among people aged ≥ 65 years (AAPC 1.35%), followed by Lesotho (AAPC 1.04%). Additionally, China showed the greatest YLL decrease (AAPC − 7.40%/year), and Bangladesh showed the greatest YLD decrease (AAPC − 4.12%/year) (see Fig. 3 , Supplementary Table 3, Supplementary Fig. 11). Risk factors A comprehensive analysis of global data from 1990 to 2021 identified three major risk factors contributing to TB DALYs among individuals aged 65 years and older: high fasting plasma glucose levels, tobacco use, and alcohol use. Of these three factors, only the number of TB DALYs attributable to high fasting plasma glucose levels was rising (from 1.40 million in 1990 to 1.90 million in 2021), while the number attributable to both smoking and alcohol consumption was falling. In 2021, these factors accounted for 248, 157, and 120 DALYs per 100,000 people, respectively. The descending order of the AAPCs from 1990 to 2021 for these factors was as follows: high fasting plasma glucose levels (-1.76%), alcohol use (-2.75%), and tobacco use (-4.08%). In high-SDI countries, the greatest reduction in burden was linked to tobacco use (AAPC − 0.65%) and high alcohol use (-5.18%). Conversely, low-SDI countries bore the highest burden for all three risk factors (Table 2 ). Table 2 Risk factors for age-standardized TB-related DALYs and AAPC, among people aged ≥ 65 years, 1990–2021. Risk factors by SDI DALY (95% UI) AAPC (%, 95% CI)) No. of people with TB in 1990 (000s) ASR 1990(per 100,000) No. of people with TB in 2021 (000s) ASR 2021(per 100,000) High fasting plasma glucose Global 1396.79(0.97 to 1.90) 428.58(298.87 to 581.83) 1900.77(1360.13 to 2509.32) 247.75(177.34 to 327.04) -1.76 (-1.85 to -1.67) High SDI 51.836.41(37.53 to 68.11) 49.52(35.84 to 65.09) 32.26(22.82 to 43.23) 14.92(10.6 to 19.95) -3.83(-4.04 to -3.61) High-middle SDI 99.733(68.32 to 136.86) 119.19(81.65 to 163.5) 72.34(51.15 to 97.67) 39.5(27.95 to 53.31) -3.43(-3.59 to -3.26) Middle SDI 254.86(173.61 to 358.90) 562.17(389.07 to 766.97) 409.59(287.27 to 557.51) 230.32(161.68 to 308.35) -2.88(-3.03 to -2.72) Low-middle SDI 576.03(390.25 to 792.76) 1324.77(896.45 to 1828.17) 867.68(611.81 to 1160.26) 776.06(547.72 to 1038.83) -1.7(-1.91 to -1.48) Low SDI 413.46(286.44 to 563.39) 1678.42(1142.51 to 2362.43) 517.84 (363.15 to 693.52) 1171.25(820.66 to 1592.95) -1.15(-1.37 to -0.94) Tobacco Global 1903.18(1438.26 to 2438.43) 565.78(426.74 to 726.04) 1220.30 (923.99 to 1559.86) 156.51(118.49 to 200.24) -4.08(-4.25 to -3.91) High SDI 91.37(71.49 to 111.73) 87.49(68.44 to 107.02) 23.02 (16.94 to 30.04) 11.07(8.16 to 14.42) -6.52(-6.74 to -6.3) High-middle SDI 195.83(144.97 to 256.42) 227.18(168 to 297.79) 87.17(63.87 to 116.21) 46.75(34.24 to 62.36) -5.07(-5.35 to -4.8) Middle SDI 218.73(157.30 to 305.78) 751.86(554.21 to 961) 158.46(114.37 to 213.24) 160.45(119.34 to 209.83) -4.92(-4.98 to -4.85) Low-middle SDI 798.90(579.83 to 1048.81) 1737.15(1254.61 to 2291.04) 575.47(422.12 to 761.57) 497.52(364.15 to 659.95) -3.99(-4.14 to -3.84) Low SDI 597.37(441.27 to 761.14) 1300.99(932.36 to 1825.63) 375.51(279.76 to 489.88) 424.95(306.93 to 573.18) -3.61(-3.78 to -3.44) Alcohol use Global 938.45(-475.47 to 3592.12) 279.16(-141.43 to 1070.85) 925.99(-563.30 to 3517.73) 119.15(-72.24 to 453.72) -2.75(-2.85 to -2.65) High SDI 71.72(-71.02 to 241.96) 68.68(-68.01 to 231.78) 28.86(-25.41 to 100.95) 13.4(-11.94 to 46.53) -5.18(-5.38 to -4.97) High-middle SDI 115.28(-97.82 to 411.30) 134.59(-113.31 to 481.98) 58.27(-49.74 to 206.27) 31.47(-26.72 to 111.65) -4.67(-5.02 to -4.32) Middle SDI 195.47(-69.89 to 798.92) 339.41(-187.87 to 1307.27) 216.12(-111.64 to 858.60) 116.42(-79.69 to 435.86) -3.41(-3.54 to -3.29) Low-middle SDI 284.97(-86.86 to 1176.28) 610.28(-186.83 to 2525.76) 353.07(-186.04 to 1407.13) 302.71(-158.13 to 1214.49) -2.29(-2.48 to -2.1) Low SDI 270.51(-152.77 to 1034.39) 1161.1(-409.5 to 4773.37) 269.19(-186.09 to 1003.70) 591.94(-299.83 to 2372.42) -2.19(-2.3 to -2.07) Discussion For the first time, we systematically estimated the global change in tuberculosis burden among older adults. During the past three decades, the burden of tuberculosis among the elderly has consistently increased. In 2021, 8.64 million elderly individuals globally experienced DALYs due to tuberculosis, accounting for approximately one-fifth of total global DALYs. While age-standardized global DALY rates decreased, the total number of YLDs increased by more than 30% during this time. The reduction in TB-related DALYs among older adults has been markedly slower compared to the general population, with significant disparities observed between countries at different sociodemographic levels. Achieving optimal blood glucose control remains a critical challenge in reducing the TB burden among the elderly. This study may provide the scientific basis for WHO and countries worldwide to improve the current status of the TB burden. Global trends The proportion of DALYs attributed to elderly tuberculosis patients has steadily increased, reaching approximately one-fifth of the total TB burden by 2021. This trend reflects both the growing elderly population and their increased vulnerability to TB reactivation due to immunosenescence[ 9 ] and comorbidities. Although the age-standardized DALY rate for elderly TB patients has gradually decreased, the decline has been slower than in the overall population. This persistent, higher burden of TB in older adults is likely due to age-related comorbidities and diagnostic delays. Addressing TB in this population is essential for achieving the End TB targets. Due to the insidious nature of symptoms in the elderly 10 , coupled with immunosenescence, multiple comorbidities, and a higher likelihood of adverse reactions[ 11 ], tuberculosis prognosis is generally poorer in this population. This underscores the importance of strengthening screening for early detection, implementing treatment adherence interventions[ 12 , 13 ], and providing social protection interventions (e.g., cash transfers and economic incentives) [ 14 – 16 ]. The observed decline in YLLs alongside the rise in YLDs suggests a shift in the tuberculosis burden, with improved treatment and management reducing mortality but leaving significant long-term health impairments, particularly in the elderly. This trend highlights the pressing need to focus on quality of life and long-term care for TB survivors, a shift with profound public health implications. Healthcare systems must prepare for increased demand for long-term care, rehabilitation, and support services, which will inevitably lead to higher healthcare costs and reduced productivity. The economic burden extends to families and communities, necessitating a comprehensive response. Enhancing public health strategies to ensure early diagnosis, treatment adherence, and stigma reduction is crucial. Governments and health organizations need to allocate more resources toward TB management, develop new treatments, and enhance support for the quality of life of TB survivors. Public health campaigns should prioritize early diagnosis and treatment adherence to prevent long-term disabilities. Sex and age differences in burden of T1DM among older people We further analyzed the TB DALY burden by gender and found that men consistently exhibited a higher burden than women across all age groups, corroborating previous research [ 17 , 18 ]. Specifically, the male DALY rate was significantly higher than the female rate, underscoring the considerable disadvantage men face in seeking and accessing TB care in many contexts [ 19 ]. Additionally, men exhibited higher rates of tobacco and alcohol use, alongside other established TB risk factors [ 20 – 22 ]. Given their roles and occupational hazards, men are more likely to be exposed to Mycobacterium tuberculosis 18 . Consequently, it is crucial to enhance awareness regarding glycemic control and occupational exposure related to TB among men. Additionally, we analyzed the change in TB burden across different age groups over 30 years. Although the percentage change consistently and steadily decreased across all age groups, those aged 70–74 and 85–89 showed higher and lower percentage changes, respectively. Previous studies have shown a higher burden of MTB infection among the elderly[ 23 ] and an association between unsuccessful treatment and increasing age[ 24 ]. With global aging, TB in the elderly population warrants attention. Worldwide, aging-related epidemiological data that could facilitate healthcare planning are scarce, but healthcare needs could increase. Therefore, increased investment in health resources for projects such as screening, diagnosis, and treatment of TB infection in adolescents and the elderly would be essential in reducing the TB burden attributable to DALYs. Sociodemographic differences in burden of older people with TB Age-standardized DALY, YLL, and YLD rates of TB inversely correlate with SDI, and DALY decline is faster in countries with higher SDI levels. As SDI decreases, TB burden in the elderly gradually increases. Elderly populations in countries with higher SDI may experience better health profiles, including improved nutritional status, more comprehensive healthcare services, and lower chronic disease prevalence, potentially reducing TB risk[ 25 ]. Additionally, these populations may have better access to TB diagnosis and treatment services, facilitating early detection and treatment, thereby lowering DALYs. The impact of risk factors such as high fasting plasma glucose, tobacco, and alcohol use on the TB burden in the elderly varies across SDI levels. In 1990, tobacco was the leading risk factor for TB DALYs in high-SDI countries, but by 2021, its impact had decreased, falling behind high fasting plasma glucose and alcohol use. Similarly, in low-SDI countries, the age-standardized rate of DALYs attributed to tobacco dropped from the second to the third position. This may reflect the success of tobacco control initiatives in these countries. Unlike high fasting plasma glucose and alcohol use, the relationship between tobacco and SDI is not strictly monotonic; the highest age-standardized rate of DALYs attributed to tobacco was observed in low-middle SDI countries rather than low-SDI countries, which could be related to consumption capacity. Priority should be given to the 30 high TB burden countries and 3 global TB watchlist countries,, as they account for 86.31% of global DALYs. India has the highest number of TB DALYs globally, while the Central African Republic has the highest age-standardized rate of DALYs. DALYs have decreased in all 21 regions and the majority of countries, but at varying rates. East Asia has experienced the fastest decline, likely due to improvements in public health policies and healthcare systems in the region [ 26 ]. China has achieved the fastest decline in DALYs among 33 countries due to active TB control measures implemented over the past decades, leading to significant reductions in prevalence and incidence rates. Over the last three decades, China has also transitioned from a predominance of infectious diseases to non-communicable diseases (NCDs) [ 27 ]. Sub-Saharan Africa has the slowest decline, with Zimbabwe and Lesotho experiencing increases in DALYs. Challenges such as the HIV/AIDS epidemic, poverty, inadequate infrastructure, and limited healthcare resources are prevalent in these countries or regions [ 28 , 29 ]. The significant disparities in TB burdens across different regions and countries highlight substantial inequity, potentially influenced by factors including economic development levels[ 30 ], public health policies[ 31 ], social protection expenditures[ 32 ], and sociocultural backgrounds[ 33 ]. TB control strategies must be tailored to the specific challenges of different regions and countries. Strengthening international cooperation and supporting developing countries in building TB control capacity are crucial for achieving global TB elimination. Risk factors in burden of TB among older people High fasting plasma glucose or diabetes and tobacco use were identified as major contributors to DALYs from TB among people aged ≥ 65 years. Diabetes is 1 of the 4 major types of NCDs and the ninth leading cause of death globally [ 34 ]. The IDF estimates that 537 million people had diabetes in 2021, a number projected to increase to 643 million and 784 million in 2030 and 2045, respectively [ 35 ]. This continuing increasing trend of diabetes for decades may explain the slower decrease in TB-related DALYs. Meanwhile, almost half of the population with diabetes is undiagnosed and untreated. Hyperglycemia is often severe, and many patients with TB and diabetes have a significant cardiovascular disease risk and severe TB [ 36 ], undoubtedly leading to high DALYs. Diabetes can increase susceptibility to tuberculosis, lead to poorer treatment outcomes, and complicate its management [ 37 ]. Elevated fasting plasma glucose has been shown to contribute to the global TB burden [ 38 ], including the development of drug resistance [ 39 ]. Countries with low-middle and low SDI had higher diabetes-related DALYs because three-quarters of diabetes patients live in low- and middle-income countries [ 35 ]. Tobacco smoking is a proven independent risk factor for TB and significantly impacts many aspects of the disease, including development, treatment outcomes, and mortality[ 40 – 42 ]. While tobacco use presents an avoidable threat to public health worldwide, the global prevalence among people aged 15 years and older decreased from 32.7% in 2000 to 21.7% in 2020[ 43 ], consistent with the trend in TB-related DALYs. Notably, diabetes-related DALYs were strongly linked to tobacco use[ 44 ]. Additionally, our findings showed that alcohol use contributed to TB DALYs among older people. Alcohol is the leading risk factor for premature mortality and disability among those aged 20 to 39 years, accounting for 13% of all deaths in this age group. In contrast, individuals aged ≥ 65 years had lower percentages (< 5%) of alcohol-attributable deaths [ 45 ]. Alcohol use disorders increased TB risk due to alcohol-related social mixing patterns and the influence of alcohol and alcohol-related conditions on the immune system [ 46 ]. Therefore, we recommend minimizing or eliminating smoking and alcohol consumption. Studies have shown that controlling smoking and alcohol consumption can reduce tuberculosis deaths in the elderly [ 47 ]. Although total alcohol consumption per capita globally decreased slightly from 5.7 liters in 2010 to 5.5 liters in 2019 (a 4.5% relative reduction) [ 45 ], alcohol-related DALYs decreased globally and across SDI levels. Our findings highlight the importance of providing better care and access to case-detection, intervention, and clinical management for TB, diabetes, tobacco use, and alcohol use systematically. Studies have shown that, for older people, controlling smoking and alcohol consumption can help reduce tuberculosis deaths [ 47 ]. Strengths and limitations of this study This study has several strengths and novel aspects. First, aligning TB control with health economics by focusing on the elderly population elucidates specific disease burden characteristics and influencing factors within this demographic, providing a foundation for policy preferences and strategic development. Second, the DALY metric, which integrates YLLs and YLDs, offers a comprehensive measure of the disease's impact on the population. Third, the GBD study furnishes global, regional, and country-specific data, facilitating cross-regional comparisons and enhancing the understanding of the geographic distribution and temporal trends in TB burden. Finally, analyzing data from 1990 to 2021 allows for the observation of TB burden trends over time, aiding in the assessment of control strategy effectiveness and the adjustment of future policies. Despite leveraging a comprehensive global dataset with detailed country-level and regional data, this study has several limitations. First, data completeness and quality from certain countries or regions may be suboptimal, potentially affecting the accuracy and reliability of the analysis. The inherent variability in data quality across countries and years often necessitates using estimates, leading to wider confidence intervals and increased uncertainty in the absence of robust data. Second, GBD studies predominantly provide descriptive analyses, limiting the ability to infer causality. To gain a deeper understanding of the factors influencing the TB burden, it is crucial to combine these findings with other research methodologies. Third, the database encompasses a limited range of influencing factors, potentially overlooking contributions from other critical determinants, such as malnutrition. Future research should incorporate findings from previous studies to address these additional factors and provide a more comprehensive analysis. Conclusions The tuberculosis burden among older adults has significantly increased, with disparities observed across countries with varying sociodemographic indices, accounting for nearly one-fifth of the global TB burden by 2021. These findings offer crucial insights for policy development by the WHO and global health leaders. Abbreviations TB Tuberculosis DALY Disability adjusted life years YLL Years of life lost YLD Years lived with disability AAPC Average annual percentage changes GBD Global Burden of Disease UI Uncertainty intervals CI Confidence intervals ASR Age-standardized rates SDI Socio-Demographic Index Declarations Ethical approval and consent to participate The protocol of the GBD 2021 has been approved by the research ethics board at the University of Washington. The GBD 2021 shall be conducted in full compliance with University of Washington policies and procedures, as well as applicable federal, state, and local laws. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Funding: This work was supported by the National Science and Technology Major Project of China (grant 2017ZX10201302-001) and the Tuberculosis Control and Prevention Programme of China CDC. The funder of the study had no role in the study design, data collection, data analysis, data interpretation, or the writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. Author Contribution YS Liu: first draft writing, review, editing, conceptualization, methodology, data acquisition; CY Z and T L: data acquisition, figures, review and editing; MK F, YH L, H C, J C: review and editing; H Z and ZG G: conceptualization, review, editing, methodology and supervision. Acknowledgements The authors appreciate the works by the GBD Study 2021 collaborators. Data Availability The datasets analysed during the current study are available at https://vizhub.healthdata.org/gbd-results/. References Global tuberculosis report 2023. Licence: CC by-NC-SA 3.0 IGO. Geneva: World Health Organization; 2023. Uplekar M, Weil D, Lonnroth K, et al. WHO’s new End TB Strategy. Lancet. 2015;385:1799–801. 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. Lancet Infect Dis. 2024 2024;24(7):698–725. 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Available from: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=35432348&query_hl=1 10.3389/fimmu.2022.864817 Jinyi W, Zhang Y, Wang K, Peng P. Global, regional, and national mortality of tuberculosis attributable to alcohol and tobacco from 1990 to 2019: a modelling study based on the Global Burden of Disease study 2019. J Glob Health. 2024. 2024;14:4023. Available from: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=38175959&query_hl=1 10.7189/jogh.14.04023 Additional Declarations No competing interests reported. Supplementary Files SupplementaryMaterials.pdf Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7602192","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":535407488,"identity":"a170b216-7b7b-4d24-853e-5f62223ab309","order_by":0,"name":"Yushu Liu","email":"","orcid":"","institution":"Tuberculosis Prevention and Control Institute, Beijing Center for Disease Prevention and Control","correspondingAuthor":false,"prefix":"","firstName":"Yushu","middleName":"","lastName":"Liu","suffix":""},{"id":535407489,"identity":"c5da2466-ae19-4b8f-bcc4-996af2fb974e","order_by":1,"name":"Canyou Zhang","email":"","orcid":"","institution":"National Center for Tuberculosis Control and Prevention, China CDC","correspondingAuthor":false,"prefix":"","firstName":"Canyou","middleName":"","lastName":"Zhang","suffix":""},{"id":535407490,"identity":"e6dd4243-440a-4b23-9347-9b5107ed542a","order_by":2,"name":"Tao Li","email":"","orcid":"","institution":"National Center for Tuberculosis Control and Prevention, China CDC","correspondingAuthor":false,"prefix":"","firstName":"Tao","middleName":"","lastName":"Li","suffix":""},{"id":535407491,"identity":"a0d9649e-9936-4f61-8d20-1807e80920df","order_by":3,"name":"Mingkuan Fan","email":"","orcid":"","institution":"Medical College of Xiangyang Polytechnic","correspondingAuthor":false,"prefix":"","firstName":"Mingkuan","middleName":"","lastName":"Fan","suffix":""},{"id":535407492,"identity":"12e686c3-7f79-438e-a6ee-ad7cb5df2a5a","order_by":4,"name":"Yuhong Li","email":"","orcid":"","institution":"National Center for Tuberculosis Control and Prevention, China CDC","correspondingAuthor":false,"prefix":"","firstName":"Yuhong","middleName":"","lastName":"Li","suffix":""},{"id":535407493,"identity":"aa235921-ef9a-4a76-b31e-6a2b74391f52","order_by":5,"name":"Hui Chen","email":"","orcid":"","institution":"National Center for Tuberculosis Control and Prevention, China CDC","correspondingAuthor":false,"prefix":"","firstName":"Hui","middleName":"","lastName":"Chen","suffix":""},{"id":535407494,"identity":"4d6e8a5c-8c72-4768-8048-d148011da25f","order_by":6,"name":"Jun Cheng","email":"","orcid":"","institution":"National Center for Tuberculosis Control and Prevention, China CDC","correspondingAuthor":false,"prefix":"","firstName":"Jun","middleName":"","lastName":"Cheng","suffix":""},{"id":535407495,"identity":"61ed0838-b333-4397-b1cb-97a5ea5f7ada","order_by":7,"name":"Hui Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3UlEQVRIiWNgGAWjYDACCSBmbGDg4WfgYTgAYROrRbKBVC0MBgd4wHzCWuRnNz97+HXHYRnj42cPHi6osZPtb2B+9gCfFsY5x8yNZc8c5jE7k5dweMaxZOMZB9jMDfBpYZZIMJOWbANqucFjcJiH7UDiBgYeNgl8Wtgk0r+BtRjPAGn5R4QWHokcM8mPQC0GEkAtvG1EaJGQyCmTZmxL55E4kwPU0gf0y2E2M7xa5Gekb5P82WZtz99+xvgzzzdgiLU3P8OrBQSYeVC5hNQDAeMPIhSNglEwCkbBCAYAcNdFRsZVUiwAAAAASUVORK5CYII=","orcid":"","institution":"National Center for Tuberculosis Control and Prevention, China CDC","correspondingAuthor":true,"prefix":"","firstName":"Hui","middleName":"","lastName":"Zhang","suffix":""},{"id":535407496,"identity":"e5caf823-f775-4019-b66c-4264b9256088","order_by":8,"name":"Zhidong Gao","email":"","orcid":"","institution":"Tuberculosis Prevention and Control Institute, Beijing Center for Disease Prevention and Control","correspondingAuthor":false,"prefix":"","firstName":"Zhidong","middleName":"","lastName":"Gao","suffix":""}],"badges":[],"createdAt":"2025-09-12 16:08:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7602192/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7602192/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":94823185,"identity":"3c0607fb-9158-4fa1-b82d-45bfe75346f1","added_by":"auto","created_at":"2025-10-31 06:46:40","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":2068189,"visible":true,"origin":"","legend":"","description":"","filename":"GlobalBurdenofTuberculosisinAdultsAged65YearsandOlder19902021APopulationBasedStudy4.docx","url":"https://assets-eu.researchsquare.com/files/rs-7602192/v1/255de9926b29138c07626027.docx"},{"id":94823671,"identity":"046c214b-22ba-4ab9-9902-8abbeb7f0d9b","added_by":"auto","created_at":"2025-10-31 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10:41:03","extension":"html","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":165154,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7602192/v1/16fbb77d449ffa655bdd2c36.html"},{"id":94753605,"identity":"41e46ef3-47cb-4104-a452-69a70803be5d","added_by":"auto","created_at":"2025-10-30 10:41:03","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":135905,"visible":true,"origin":"","legend":"\u003cp\u003eThe changes in the proportion of DALY cases among tuberculosis patients aged over 65 years to the overall tuberculosis patients from 1990 to 2021.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7602192/v1/37ed2fd7759e75ec2f1c55b7.png"},{"id":94753604,"identity":"60df04bd-e02d-4bb0-8ee0-992bcccaeaa5","added_by":"auto","created_at":"2025-10-30 10:41:03","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":540088,"visible":true,"origin":"","legend":"\u003cp\u003eMap showing global age-standardized DALY rates among people with tuberculosis aged ≥65 years, 1990-2021.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7602192/v1/73b57f2abdcd07c77a4f7b83.png"},{"id":94753606,"identity":"893a2440-f496-4ada-a417-f92b217c082f","added_by":"auto","created_at":"2025-10-30 10:41:03","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":534125,"visible":true,"origin":"","legend":"\u003cp\u003eMap showing average annual percentage change in global DALYs among people with tuberculosis aged ≥65 years, 1990–2021.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7602192/v1/5f94843e8d0da43c1a21388d.png"},{"id":96362707,"identity":"1923607c-88fd-4dc5-accb-120ff2cefdc1","added_by":"auto","created_at":"2025-11-20 09:45:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2523463,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7602192/v1/8afb0527-20e5-44f0-8be1-3998afb7b84d.pdf"},{"id":94753609,"identity":"463ae875-a710-4a03-b7ec-308f70a639c1","added_by":"auto","created_at":"2025-10-30 10:41:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":2454360,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterials.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7602192/v1/93176677f42edc150d696539.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Global Burden of Tuberculosis in Adults Aged 65 Years and Older, 1990–2021: A Population-Based Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThree decades after the World Health Organization (WHO) declared tuberculosis (TB) a global public health emergency, the disease remains the second leading cause of death from a single infectious agent, following coronavirus disease (COVID-19) in 2022. TB was responsible for nearly double the number of deaths compared to HIV/AIDS. In 2022, over 10\u0026nbsp;million people fell ill with TB, and 1.3\u0026nbsp;million people died from the disease[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. To combat TB, the WHO launched the End TB Strategy[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], aiming for a 90% reduction in TB incidence and a 95% reduction in TB-related deaths by 2035. Despite substantial progress in TB control over the past two decades, current trends indicate that meeting these targets remains a significant challenge. The pace of decline has been uneven, with older adults experiencing the slowest reduction in TB burden[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Greater focus and integrated strategies are required, particularly for vulnerable groups, including the elderly[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe impact of an aging population on TB epidemiology demands significant attention. By 2050, the global population of older adults is expected to reach 2.1\u0026nbsp;billion, accounting for 22% of the total population[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Due to immune decline, physiological changes, malnutrition, and numerous other factors, older adults are more susceptible to various diseases, increasing their risk of tuberculosis[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In this population, TB is often linked to the reactivation of latent infections[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The WHO estimates that one-third of the global population is infected with TB, placing older adults at a heightened risk of developing active disease.\\ The elderly population experiences a higher risk of morbidity and mortality than other populations due to the high rate of latent tuberculosis infection, coupled with factors such as declining immune function, insufficient care, and a high prevalence of underlying diseases[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], making them a priority population for tuberculosis control. However, the global burden of TB among older adults, measured in disability-adjusted life years (DALYs), remains underexplored.\u003c/p\u003e\u003cp\u003eTo achieve End TB targets, the impact of population aging on TB epidemiology and strategy must be considered. TB causes lifelong disability, a factor not captured by cross-sectional prevalence. DALYs offer a comprehensive measure by accounting for years lost to ill health, disability, or premature death. Drawing on data from the Global Burden of Disease (GBD) 2021 study, we analyzed the global, regional, and national burden of TB among older adults. Our analysis focused on DALYs, years of life lost (YLLs), and years lived with disability (YLDs) from 1990 to 2021, while also investigating key factors contributing to the DALY burden in older TB patients.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy population and data collection\u003c/h2\u003e\u003cp\u003eThe global burden of TB in older adults (aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years) was analyzed using data from the Global Burden of Disease (GBD) Study 2021. This comprehensive dataset includes 369 diseases and 87 risk factors across 204 countries and territories, providing a robust foundation for analysis. Data were sourced from the Global Health Data Exchange and include repeated cross-sectional data spanning 1990 to 2021. We extracted information on TB, including location, age, and sex-specific DALYs, YLLs, YLDs, alongside DALYs attributable to individual risk factors, all accompanied by 95% uncertainty intervals (UIs). Countries and territories were categorized into 21 regions based on epidemiological and geographical similarities and further categorized into five sociodemographic index (SDI) levels: low, low-middle, middle, high-middle, and high SDI. The SDI, a composite measure, is derived from lag-distributed income per capita, the total fertility rate among females under 25, and the average years of schooling in adults aged\u0026thinsp;\u0026ge;\u0026thinsp;15 years. Data were stratified by seven age groups (65\u0026ndash;69, 70\u0026ndash;74, 75\u0026ndash;79, 80\u0026ndash;84, 85\u0026ndash;89, 90\u0026ndash;94, and \u0026ge;\u0026thinsp;95 years) and analyzed for both sexes. Special attention was given to the 30 high TB burden countries, including Angola, Bangladesh, Brazil, Central African Republic, China, Congo, Democratic People's Republic of Korea, Democratic Republic of the Congo, Ethiopia, Gabon, India, Indonesia, Kenya, Lesotho, Liberia, Mongolia, Mozambique, Myanmar, Namibia, Nigeria, Pakistan, Papua New Guinea, Philippines, Sierra Leone, South Africa, Thailand, Uganda, United Republic of Tanzania, Viet Nam, and Zambia, as well as the three countries on the global TB watchlist: Cambodia, the Russian Federation, and Zimbabwe.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eStatistical analyses\u003c/h3\u003e\n\u003cp\u003eA descriptive analysis was conducted to characterize the global TB burden among adults aged 65 years and older. The burden was quantified by calculating DALYs, YLLs, YLDs, age-standardized rates (ASRs) with corresponding 95% uncertainty intervals (UIs), and average annual percentage changes (AAPCs) with 95% confidence intervals (CIs). These metrics were computed to assess the disease burden attributable to risk factors across different age groups, sexes, years, and locations. All estimates incorporated uncertainty, accounting for variability in primary data sources, model assumptions, measurement errors, and data handling processes. This uncertainty was quantified statistically and reflected in the 95% UIs for each location and estimate. The UIs were derived from 1,000 draw-levels sampled from the posterior distribution of models, with the 95% UIs defined as the range between the 2.5th and 97.5th percentiles. ASRs, calculated using direct standardization, applied age-specific rates to a standard age distribution to compare the burden of disease across populations with different age structures. This standardization helped eliminate the effects of age differences in the population, providing a clearer understanding of the true variations in disease burden. AAPCs captured the average annual rate of change over the study period, indicating whether the burden was increasing, decreasing, or stable. A rate was considered to be trending upward or downward if the annual percentage change and its 95% CI were both positive or negative, respectively. AAPCs were calculated using the standard formula. All analyses were conducted in R software (R Core Team, version 4.4.1, Vienna, Austria).\u003cdiv id=\"Equa\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equa\" name=\"EquationSource\"\u003e\n$$\\:\\begin{array}{c}Age\\:standardised\\:rate=\\frac{{\\sum\\:}_{i=1}^{A}{a}_{i}{w}_{i}}{{\\sum\\:}_{i=1}^{A}{w}_{i}}\\#\\left(1\\right)\\end{array}$$\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003ewhere \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{a}_{i}\\)\u003c/span\u003e\u003c/span\u003e is the age-specific death rate and \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{w}_{i}\\)\u003c/span\u003e\u003c/span\u003e is the weight in the same age subgroup of the chosen reference standard population (in which \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:i\\)\u003c/span\u003e\u003c/span\u003e denotes the \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{i}^{th}\\)\u003c/span\u003e\u003c/span\u003e age class) and \u003cem\u003eA\u003c/em\u003e is the upper age limit.\u003cdiv id=\"Equb\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equb\" name=\"EquationSource\"\u003e\n$$\\:\\begin{array}{c}AAPC=\\left\\{\\text{exp}\\left(\\frac{\\sum\\:{w}_{i}{b}_{i}}{{w}_{i}}\\right)-1\\right\\}\\times\\:100\\#\\left(2\\right)\\end{array}$$\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{b}_{i}\\)\u003c/span\u003e\u003c/span\u003e is the slope coefficient for the \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{i}^{th}\\)\u003c/span\u003e\u003c/span\u003e segment, with \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:i\\)\u003c/span\u003e\u003c/span\u003e indexing the segments in the desired range of years, and \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{w}_{i}\\)\u003c/span\u003e\u003c/span\u003e is the length of each segment in the range of years.\u003c/p\u003e\n\u003ch3\u003ePatient and public involvement\u003c/h3\u003e\n\u003cp\u003eThe Global Burden of Disease Study represents a collaborative scientific initiative, enabling comparative analysis of the impact of various health conditions across age, sex, and geographic regions at specific points in time. This work has garnered significant attention in the scientific, policy, and public spheres worldwide. Our study utilized secondary data from this collaborative effort, and we did not have direct access to individual participants. No patients were involved in formulating the research question, defining the outcome measures, or contributing to the design and execution of the study.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eGlobal trends\u003c/h2\u003e\u003cp\u003eGlobally, in 2021, an estimated 8.63\u0026nbsp;million (95% \u003cem\u003eUI\u003c/em\u003e 7.75\u0026ndash;9.74) people aged 65 years and older experienced DALYs due to TB. The age-standardized DALY rate was 1,122 per 100,000 population (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The proportion of DALYs due to tuberculosis among older people has shown an upward trend relative to the overall number of DALYs in the entire population, increasing from 12.45% in 1990 to 18.38% in 2021 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The number of DALYs in the 65\u0026thinsp;+\u0026thinsp;population gradually increased to a peak of 11.09\u0026nbsp;million before 1998, then declined significantly after 2000 and remained virtually unchanged after 2015. In contrast, the number of DALYs in the total population declined consistently from 1990 to 2021 (see supplementary Fig.\u0026nbsp;1). Furthermore, the age-standardized DALY rate for tuberculosis in the elderly has consistently been higher than that of the total population, and its rate of decline has been slower (see supplementary Fig.\u0026nbsp;2). The age-standardized DALY rate of TB among this age group decreased by 64%, from 3,122 per 100,000 population in 1990 to 1,122 per 100,000 population in 2021, with an average annual trend of -3.26% (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Furthermore, YLLs and YLDs varied inversely. The number of YLLs for tuberculosis in people over 65 years of age decreased while the number of YLDs increased from 0.67\u0026nbsp;million to 0.88\u0026nbsp;million (see supplementary Fig.\u0026nbsp;3). Notably, the proportion of YLDs in DALYs increased from 6.5% to 10.2% (see supplementary Fig.\u0026nbsp;4). The age-standardized DALY rate for the population aged 65 and above increased from 1.89 times that of the overall population in 1990 to 1.93 times in 2021 (see supplementary Fig.\u0026nbsp;5).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAge-standardized DALY and AAPC of tuberculosis in people aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years at the global and regional level, 1990\u0026ndash;2021.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eDALY (95% UI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eAAPCs (%, 95% CI)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo. of people with TB in 1990 (000s)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eASR 1990(per 100,000)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNo. of people with TB in 2021 (000s)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eASR 2021(per 100,000)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGlobal\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10295.23 (8650.21 to 11775.70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3122.35 (2620.87 to 3573.96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8633.87\u003c/p\u003e\u003cp\u003e(7754.21469 to 9740.3195)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e1122 (1007.14 to 1265.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-3.26\u003c/p\u003e\u003cp\u003e(-3.38 to -3.15)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3891.55\u003c/p\u003e\u003cp\u003e(3410.38 to 4443.34)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2080.73(1820.33 to 2377.94)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3304.96\u003c/p\u003e\u003cp\u003e(2946.33 to 3704.08)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e787.04(701.66 to 882.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-3.1\u003c/p\u003e\u003cp\u003e(-3.18 to -3.01)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6403.68\u003c/p\u003e\u003cp\u003e(4950.23 to 7739.47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4546.4(3503.06 to 5515.09)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5328.91\u003c/p\u003e\u003cp\u003e(4665.72 to 6396.93)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1532.45(1339.43 to 1840.16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-3.46\u003c/p\u003e\u003cp\u003e(-3.62 to -3.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge group (years)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e65\u0026ndash;69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3831.00\u003c/p\u003e\u003cp\u003e(3214.66 to 4342.91)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3099.28(2600.66 to 3513.41)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2902.57\u003c/p\u003e\u003cp\u003e(2615.92 to 3298.03)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1052.26(948.34 to 1195.62)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-3.42\u003c/p\u003e\u003cp\u003e(-3.72 to -3.11)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e70\u0026ndash;74\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3020.10\u003c/p\u003e\u003cp\u003e(2542.78 to 3458.11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3567.28(3003.48 to 4084.65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2368.52\u003c/p\u003e\u003cp\u003e(2124.03 to 2661.18)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1150.67(1031.89 to 1292.84)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-3.61\u003c/p\u003e\u003cp\u003e(-3.89 to -3.33)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e75\u0026ndash;79\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e1925.98\u003c/p\u003e\u003cp\u003e(1629.26 to 2224.01)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e3128.84(2646.82 to 3613.01)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e1601.92\u003c/p\u003e\u003cp\u003e(1462.00 to 1792.15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e1214.64(1108.54 to 1358.88)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-3.02\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e(-3.24 to -2.79)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e80\u0026ndash;84\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1033.15\u003c/p\u003e\u003cp\u003e(864.77 to 1192.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2920.48(2444.53 to 3369.67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1057.05\u003c/p\u003e\u003cp\u003e(945.87 to 1189.34)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1206.91(1079.97 to 1357.96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-2.8\u003c/p\u003e\u003cp\u003e(-3.17 to -2.43)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e85\u0026ndash;89\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e374.09\u003c/p\u003e\u003cp\u003e(309.89 to 429.83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2475.6(2050.74 to 2844.47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e493.18\u003c/p\u003e\u003cp\u003e(430.93 to 558.23)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1078.65(942.5 to 1220.94)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-2.69\u003c/p\u003e\u003cp\u003e(-3.07 to -2.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e90\u0026ndash;94\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e90.48\u003c/p\u003e\u003cp\u003e(72.95 to 104.53)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2111.39(1702.37 to 2439.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e166.66\u003c/p\u003e\u003cp\u003e(140.38 to 191.13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e931.62(784.69 to 1068.38)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-2.73\u003c/p\u003e\u003cp\u003e(-3.01 to -2.45)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e95+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20.44\u003c/p\u003e\u003cp\u003e(15.90 to 24.26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2007.61(1562 to 2383.22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e43.97\u003c/p\u003e\u003cp\u003e(35.09 to 50.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e806.71(643.79 to 922)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-2.92\u003c/p\u003e\u003cp\u003e(-3.09 to -2.76)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSDI\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eHigh SDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e354.32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e339.89\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e154.06\u003c/p\u003e\u003cp\u003e(129.71o 174.52)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e70.61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e-4.98\u003c/p\u003e\u003cp\u003e(-5.19 to -4.78)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e(322.55 to 383.47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e(308.84 to 368.13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e(59.89 to 80.03)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eHigh-middle SDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e711.62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e848.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e370.74\u003c/p\u003e\u003cp\u003e(316.48 to 436.14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e201.88\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e-4.54\u003c/p\u003e\u003cp\u003e(-4.92 to -4.15)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e(598.31 to 833.02)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e(713.29 to 993.06)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e(172.36 to 237.42)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eMiddle SDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2798.30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3716.77\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2278.90\u003c/p\u003e\u003cp\u003e(2011.63 to 2688.42)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1008.36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e-4.13\u003c/p\u003e\u003cp\u003e(-4.21 to -4.06)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e(2338.52 to 3160.23)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e(3098.34 to 4205.43)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e(888.24 to 1189.06)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eLow-middle SDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4193.87\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9409.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e3727.99\u003c/p\u003e\u003cp\u003e(3277.99 to 4303.38)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3316.72\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e-3.33\u003c/p\u003e\u003cp\u003e(-3.54 to -3.11)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e(3474.33 to 4863.95)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e(7762.36 to 10947.08)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e(2908.32 to 3829.61)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eLow SDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2231.67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13896.98\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e2097.49(1837.91 to 2465.45)\u003c/p\u003e\u003cp\u003e(1837.91 to 2465.45)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e5979.77\u003c/p\u003e\u003cp\u003e(5224.25 to 7007.73)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e-2.73\u003c/p\u003e\u003cp\u003e(-2.85 to -2.62)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e(1825.73 to 2693.92)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e(11340.42 to 16837.12)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003eNote: Estimates are for individuals aged over 65 years. AAPCs\u0026thinsp;=\u0026thinsp;average annual percent changes. UI\u0026thinsp;=\u0026thinsp;uncertainty interval. CI\u0026thinsp;=\u0026thinsp;confidence interval. DALYs\u0026thinsp;=\u0026thinsp;disability-adjusted life years. SDI\u0026thinsp;=\u0026thinsp;Socio-Demographic Index. ASR\u0026thinsp;=\u0026thinsp;Age-standardized rate. Numbers in parentheses are 95% uncertainty intervals (cases and age-standardized rate) and 95% confidence intervals (AAPCs).\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eGlobal trends by sex\u003c/h2\u003e\u003cp\u003eFrom 1990 to 2021, the age-standardized DALYs for TB among people aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years decreased for both men and women worldwide (men: from 6.4\u0026nbsp;million to 5.3\u0026nbsp;million; women: from 3.9\u0026nbsp;million to 3.3\u0026nbsp;million). The decrease in TB DALYs was more rapid among men than women (AAPC \u0026minus;\u0026thinsp;3.46% vs. -3.10%). Notably, in all age subgroups, males had higher numbers and rates of DALYs than females (see supplementary Fig.\u0026nbsp;6). The sex ratio for DALYs due to tuberculosis was 1.65 in 1990 and decreased slightly to 1.61 by 2021 (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In 2021, the number of DALYs decreased with age for both males and females, with the highest number of DALYs in the 65\u0026ndash;69 age group, amounting to 1.9\u0026nbsp;million for males and 1.0\u0026nbsp;million for females. The highest age-standardized DALY rates for both males and females occurred at ages 80\u0026ndash;84 (1,620 vs. 902 per 100,000 population) (see supplementary Fig.\u0026nbsp;6).\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eGlobal trends by age subgroup\u003c/h3\u003e\n\u003cp\u003eThe age-standardized DALYs associated with TB among older people decreased across all age subgroups, with the most significant reductions observed among those aged 70\u0026ndash;74 years (AAPC \u0026minus;\u0026thinsp;3.61%), followed by 65\u0026ndash;69 years (\u0026minus;\u0026thinsp;3.42%) and 75\u0026ndash;79 years (\u0026minus;\u0026thinsp;3.02%). Despite these declines, the 65\u0026ndash;69 age group had the highest number of DALYs, reaching 2.9\u0026nbsp;million in 2021. The highest age-standardized rate (ASR) in 2021 was among those aged 75\u0026ndash;79 years (1,215 per 100,000 population), followed closely by those aged 80\u0026ndash;84 years (1,207 per 100,000 population). Notably, among all age subgroups, the number and rate of DALYs were higher for males than females (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, supplementary Fig.\u0026nbsp;6). In 2019 and 2021, the highest number of YLLs due to tuberculosis was in the 65\u0026ndash;69 age group (3.61\u0026nbsp;million vs. 2.62\u0026nbsp;million). Meanwhile, the age-standardized DALY rate shifted from being highest in the 70\u0026ndash;74 age group in 2019 (3,326 per 100,000) to the 80\u0026ndash;84 age group in 2021 (1,091 per 100,000). From 1990 to 2021, the number of YLDs due to tuberculosis increased across all age groups. However, the age-standardized YLD rates declined, with the slowest declines observed in the 80\u0026ndash;84 age group (\u0026minus;\u0026thinsp;1.76% per year) and the 65\u0026ndash;69 age group (\u0026minus;\u0026thinsp;1.83% per year) (see supplementary table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003eGlobal trends by sociodemographic index\u003c/h3\u003e\n\u003cp\u003eFrom 1990 to 2021, age-standardized DALYs due to TB among older adults declined across all sociodemographic groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). However, this reduction has been consistently slower in those aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years compared to the general population, irrespective of sociodemographic level (Supplementary Fig.\u0026nbsp;7). While the decline in TB-related DALYs among older adults was observed across all sociodemographic strata, the steepest reduction occurred in countries with a high SDI (AAPC \u0026minus;\u0026thinsp;4.98%), more than twice the rate of decline seen in low SDI countries (AAPC \u0026minus;\u0026thinsp;2.73%) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In 2021, DALY rates were highest in low SDI countries (5,980 per 100,000) and lowest in high SDI countries (71 per 100,000) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). With the exception of Southern Sub-Saharan Africa, where age-standardized DALY, YLL, and YLD rates initially rose before declining, all other regions exhibited a decline in these metrics as SDI increased (Supplementary Fig.\u0026nbsp;8). Globally, rising SDI was strongly associated with a marked decrease in age-standardized DALY rates. However, in countries like Somalia and the Central African Republic, age-standardized DALY, YLL, and YLD rates exceeded what would be expected based on SDI alone. Notably, Eritrea displayed a significantly higher-than-expected age-standardized YLD rate (Supplementary Fig.\u0026nbsp;9).\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eRegional trends\u003c/h2\u003e\u003cp\u003eAll 21 regions experienced a decline in TB-related DALYs among older adults between 1990 and 2021, at varying rates. East Asia saw the most pronounced reduction (AAPC \u0026minus;\u0026thinsp;6.14%), while Sub-Saharan Africa experienced the slowest decline (AAPC \u0026minus;\u0026thinsp;0.38%) (Supplementary Table\u0026nbsp;2, Supplementary Fig.\u0026nbsp;10). By 2021, the highest burden of TB DALYs among older adults was observed in Central Sub-Saharan Africa (9,899 per 100,000), Eastern Sub-Saharan Africa (8,439 per 100,000), and Western Sub-Saharan Africa (4,964 per 100,000). In contrast, the lowest DALY rates were recorded in high-income North America (17 per 100,000), Australasia (20 per 100,000), and Western Europe (35 per 100,000) (Supplementary Table\u0026nbsp;2). The geographical patterns of age-standardized YLL and YLD rates mirrored those of DALYs, with Central and Eastern Sub-Saharan Africa showing the highest values (Supplementary Table\u0026nbsp;2, Supplementary Fig.\u0026nbsp;10).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eNational trends\u003c/h2\u003e\u003cp\u003eAt the national level, TB DALYs are declining in most countries. The 30 high-burden and 3 global TB watchlist countries accounted for 86.31% of global DALYs in 2021. Among these 33 countries, India had the highest DALYs (3.10\u0026nbsp;million), YLLs (2.85\u0026nbsp;million), and YLDs (0.25\u0026nbsp;million), while the Central African Republic had the highest age-standardized DALY rate (22,785.55 per 100,000 people) (see Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Supplementary Table\u0026nbsp;3), YLL rate (21,677.08 per 100,000 people), and YLD rate (1,108.47 per 100,000 people) (see Supplementary Fig.\u0026nbsp;10, Supplementary Table\u0026nbsp;3). From 1990 to 2021, age-standardized DALY rates decreased in most countries. During this period, China had the fastest DALY decline (AAPC \u0026minus;\u0026thinsp;6.51%) among the 33 TB countries; however, only Zimbabwe (AAPC 1.35%/year) and Lesotho (AAPC 1.14%/year) showed increasing age-standardized DALY rate trends (see Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Supplementary Table\u0026nbsp;3). From 1990 to 2021, among the 30 high-burden TB countries, China had the fastest DALY decline (AAPC \u0026minus;\u0026thinsp;6.51%), while Zimbabwe had the highest increase in age-standardized TB DALYs among people aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years (AAPC 1.35%), followed by Lesotho (AAPC 1.04%). Additionally, China showed the greatest YLL decrease (AAPC \u0026minus;\u0026thinsp;7.40%/year), and Bangladesh showed the greatest YLD decrease (AAPC \u0026minus;\u0026thinsp;4.12%/year) (see Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Supplementary Table\u0026nbsp;3, Supplementary Fig.\u0026nbsp;11).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eRisk factors\u003c/h2\u003e\u003cp\u003eA comprehensive analysis of global data from 1990 to 2021 identified three major risk factors contributing to TB DALYs among individuals aged 65 years and older: high fasting plasma glucose levels, tobacco use, and alcohol use. Of these three factors, only the number of TB DALYs attributable to high fasting plasma glucose levels was rising (from 1.40\u0026nbsp;million in 1990 to 1.90\u0026nbsp;million in 2021), while the number attributable to both smoking and alcohol consumption was falling. In 2021, these factors accounted for 248, 157, and 120 DALYs per 100,000 people, respectively. The descending order of the AAPCs from 1990 to 2021 for these factors was as follows: high fasting plasma glucose levels (-1.76%), alcohol use (-2.75%), and tobacco use (-4.08%). In high-SDI countries, the greatest reduction in burden was linked to tobacco use (AAPC \u0026minus;\u0026thinsp;0.65%) and high alcohol use (-5.18%). Conversely, low-SDI countries bore the highest burden for all three risk factors (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eRisk factors for age-standardized TB-related DALYs and AAPC, among people aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years, 1990\u0026ndash;2021.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eRisk factors by SDI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003eDALY (95% UI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eAAPC (%, 95% CI))\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo. of people with TB in 1990 (000s)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eASR 1990(per 100,000)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNo. of people with TB in 2021 (000s)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eASR 2021(per 100,000)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHigh fasting plasma glucose\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGlobal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1396.79(0.97 to 1.90)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e428.58(298.87 to 581.83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1900.77(1360.13 to 2509.32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e247.75(177.34 to 327.04)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-1.76 (-1.85 to -1.67)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHigh SDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e51.836.41(37.53 to 68.11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e49.52(35.84 to 65.09)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e32.26(22.82 to 43.23)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e14.92(10.6 to 19.95)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-3.83(-4.04 to -3.61)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHigh-middle SDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e99.733(68.32 to 136.86)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e119.19(81.65 to 163.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e72.34(51.15 to 97.67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e39.5(27.95 to 53.31)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-3.43(-3.59 to -3.26)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMiddle SDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e254.86(173.61 to 358.90)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e562.17(389.07 to 766.97)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e409.59(287.27 to 557.51)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e230.32(161.68 to 308.35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-2.88(-3.03 to -2.72)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLow-middle SDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e576.03(390.25 to 792.76)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1324.77(896.45 to 1828.17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e867.68(611.81 to 1160.26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e776.06(547.72 to 1038.83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-1.7(-1.91 to -1.48)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLow SDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e413.46(286.44 to 563.39)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1678.42(1142.51 to 2362.43)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e517.84 (363.15 to 693.52)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1171.25(820.66 to 1592.95)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-1.15(-1.37 to -0.94)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTobacco\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGlobal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1903.18(1438.26 to 2438.43)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e565.78(426.74 to 726.04)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1220.30 (923.99 to 1559.86)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e156.51(118.49 to 200.24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-4.08(-4.25 to -3.91)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHigh SDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e91.37(71.49 to 111.73)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e87.49(68.44 to 107.02)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e23.02 (16.94 to 30.04)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e11.07(8.16 to 14.42)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-6.52(-6.74 to -6.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHigh-middle SDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e195.83(144.97 to 256.42)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e227.18(168 to 297.79)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e87.17(63.87 to 116.21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e46.75(34.24 to 62.36)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-5.07(-5.35 to -4.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMiddle SDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e218.73(157.30 to 305.78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e751.86(554.21 to 961)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e158.46(114.37 to 213.24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e160.45(119.34 to 209.83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-4.92(-4.98 to -4.85)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLow-middle SDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e798.90(579.83 to 1048.81)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1737.15(1254.61 to 2291.04)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e575.47(422.12 to 761.57)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e497.52(364.15 to 659.95)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-3.99(-4.14 to -3.84)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLow SDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e597.37(441.27 to 761.14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1300.99(932.36 to 1825.63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e375.51(279.76 to 489.88)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e424.95(306.93 to 573.18)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-3.61(-3.78 to -3.44)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAlcohol use\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGlobal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e938.45(-475.47 to 3592.12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e279.16(-141.43 to 1070.85)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e925.99(-563.30 to 3517.73)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e119.15(-72.24 to 453.72)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-2.75(-2.85 to -2.65)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHigh SDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e71.72(-71.02 to 241.96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e68.68(-68.01 to 231.78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e28.86(-25.41 to 100.95)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e13.4(-11.94 to 46.53)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-5.18(-5.38 to -4.97)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHigh-middle SDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e115.28(-97.82 to 411.30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e134.59(-113.31 to 481.98)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e58.27(-49.74 to 206.27)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e31.47(-26.72 to 111.65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-4.67(-5.02 to -4.32)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMiddle SDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e195.47(-69.89 to 798.92)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e339.41(-187.87 to 1307.27)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e216.12(-111.64 to 858.60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e116.42(-79.69 to 435.86)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-3.41(-3.54 to -3.29)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLow-middle SDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e284.97(-86.86 to 1176.28)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e610.28(-186.83 to 2525.76)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e353.07(-186.04 to 1407.13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e302.71(-158.13 to 1214.49)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-2.29(-2.48 to -2.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLow SDI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e270.51(-152.77 to 1034.39)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1161.1(-409.5 to 4773.37)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e269.19(-186.09 to 1003.70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e591.94(-299.83 to 2372.42)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-2.19(-2.3 to -2.07)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eFor the first time, we systematically estimated the global change in tuberculosis burden among older adults. During the past three decades, the burden of tuberculosis among the elderly has consistently increased. In 2021, 8.64\u0026nbsp;million elderly individuals globally experienced DALYs due to tuberculosis, accounting for approximately one-fifth of total global DALYs. While age-standardized global DALY rates decreased, the total number of YLDs increased by more than 30% during this time. The reduction in TB-related DALYs among older adults has been markedly slower compared to the general population, with significant disparities observed between countries at different sociodemographic levels. Achieving optimal blood glucose control remains a critical challenge in reducing the TB burden among the elderly. This study may provide the scientific basis for WHO and countries worldwide to improve the current status of the TB burden.\u003c/p\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003eGlobal trends\u003c/h2\u003e\u003cp\u003eThe proportion of DALYs attributed to elderly tuberculosis patients has steadily increased, reaching approximately one-fifth of the total TB burden by 2021. This trend reflects both the growing elderly population and their increased vulnerability to TB reactivation due to immunosenescence[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] and comorbidities. Although the age-standardized DALY rate for elderly TB patients has gradually decreased, the decline has been slower than in the overall population. This persistent, higher burden of TB in older adults is likely due to age-related comorbidities and diagnostic delays. Addressing TB in this population is essential for achieving the End TB targets. Due to the insidious nature of symptoms in the elderly\u003csup\u003e10\u003c/sup\u003e, coupled with immunosenescence, multiple comorbidities, and a higher likelihood of adverse reactions[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], tuberculosis prognosis is generally poorer in this population. This underscores the importance of strengthening screening for early detection, implementing treatment adherence interventions[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], and providing social protection interventions (e.g., cash transfers and economic incentives) [\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe observed decline in YLLs alongside the rise in YLDs suggests a shift in the tuberculosis burden, with improved treatment and management reducing mortality but leaving significant long-term health impairments, particularly in the elderly. This trend highlights the pressing need to focus on quality of life and long-term care for TB survivors, a shift with profound public health implications. Healthcare systems must prepare for increased demand for long-term care, rehabilitation, and support services, which will inevitably lead to higher healthcare costs and reduced productivity. The economic burden extends to families and communities, necessitating a comprehensive response. Enhancing public health strategies to ensure early diagnosis, treatment adherence, and stigma reduction is crucial. Governments and health organizations need to allocate more resources toward TB management, develop new treatments, and enhance support for the quality of life of TB survivors. Public health campaigns should prioritize early diagnosis and treatment adherence to prevent long-term disabilities.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003eSex and age differences in burden of T1DM among older people\u003c/h2\u003e\u003cp\u003eWe further analyzed the TB DALY burden by gender and found that men consistently exhibited a higher burden than women across all age groups, corroborating previous research [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Specifically, the male DALY rate was significantly higher than the female rate, underscoring the considerable disadvantage men face in seeking and accessing TB care in many contexts [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Additionally, men exhibited higher rates of tobacco and alcohol use, alongside other established TB risk factors [\u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Given their roles and occupational hazards, men are more likely to be exposed to \u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e \u003csup\u003e18\u003c/sup\u003e. Consequently, it is crucial to enhance awareness regarding glycemic control and occupational exposure related to TB among men.\u003c/p\u003e\u003cp\u003eAdditionally, we analyzed the change in TB burden across different age groups over 30 years. Although the percentage change consistently and steadily decreased across all age groups, those aged 70\u0026ndash;74 and 85\u0026ndash;89 showed higher and lower percentage changes, respectively. Previous studies have shown a higher burden of \u003cem\u003eMTB\u003c/em\u003e infection among the elderly[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] and an association between unsuccessful treatment and increasing age[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. With global aging, TB in the elderly population warrants attention. Worldwide, aging-related epidemiological data that could facilitate healthcare planning are scarce, but healthcare needs could increase. Therefore, increased investment in health resources for projects such as screening, diagnosis, and treatment of TB infection in adolescents and the elderly would be essential in reducing the TB burden attributable to DALYs.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\u003ch2\u003eSociodemographic differences in burden of older people with TB\u003c/h2\u003e\u003cp\u003eAge-standardized DALY, YLL, and YLD rates of TB inversely correlate with SDI, and DALY decline is faster in countries with higher SDI levels. As SDI decreases, TB burden in the elderly gradually increases. Elderly populations in countries with higher SDI may experience better health profiles, including improved nutritional status, more comprehensive healthcare services, and lower chronic disease prevalence, potentially reducing TB risk[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Additionally, these populations may have better access to TB diagnosis and treatment services, facilitating early detection and treatment, thereby lowering DALYs.\u003c/p\u003e\u003cp\u003eThe impact of risk factors such as high fasting plasma glucose, tobacco, and alcohol use on the TB burden in the elderly varies across SDI levels. In 1990, tobacco was the leading risk factor for TB DALYs in high-SDI countries, but by 2021, its impact had decreased, falling behind high fasting plasma glucose and alcohol use. Similarly, in low-SDI countries, the age-standardized rate of DALYs attributed to tobacco dropped from the second to the third position. This may reflect the success of tobacco control initiatives in these countries. Unlike high fasting plasma glucose and alcohol use, the relationship between tobacco and SDI is not strictly monotonic; the highest age-standardized rate of DALYs attributed to tobacco was observed in low-middle SDI countries rather than low-SDI countries, which could be related to consumption capacity.\u003c/p\u003e\u003cp\u003ePriority should be given to the 30 high TB burden countries and 3 global TB watchlist countries,, as they account for 86.31% of global DALYs. India has the highest number of TB DALYs globally, while the Central African Republic has the highest age-standardized rate of DALYs. DALYs have decreased in all 21 regions and the majority of countries, but at varying rates. East Asia has experienced the fastest decline, likely due to improvements in public health policies and healthcare systems in the region [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. China has achieved the fastest decline in DALYs among 33 countries due to active TB control measures implemented over the past decades, leading to significant reductions in prevalence and incidence rates. Over the last three decades, China has also transitioned from a predominance of infectious diseases to non-communicable diseases (NCDs) [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Sub-Saharan Africa has the slowest decline, with Zimbabwe and Lesotho experiencing increases in DALYs. Challenges such as the HIV/AIDS epidemic, poverty, inadequate infrastructure, and limited healthcare resources are prevalent in these countries or regions [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe significant disparities in TB burdens across different regions and countries highlight substantial inequity, potentially influenced by factors including economic development levels[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e], public health policies[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e], social protection expenditures[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], and sociocultural backgrounds[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. TB control strategies must be tailored to the specific challenges of different regions and countries. Strengthening international cooperation and supporting developing countries in building TB control capacity are crucial for achieving global TB elimination.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\u003ch2\u003eRisk factors in burden of TB among older people\u003c/h2\u003e\u003cp\u003eHigh fasting plasma glucose or diabetes and tobacco use were identified as major contributors to DALYs from TB among people aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years. Diabetes is 1 of the 4 major types of NCDs and the ninth leading cause of death globally [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. The IDF estimates that 537\u0026nbsp;million people had diabetes in 2021, a number projected to increase to 643\u0026nbsp;million and 784\u0026nbsp;million in 2030 and 2045, respectively [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. This continuing increasing trend of diabetes for decades may explain the slower decrease in TB-related DALYs. Meanwhile, almost half of the population with diabetes is undiagnosed and untreated. Hyperglycemia is often severe, and many patients with TB and diabetes have a significant cardiovascular disease risk and severe TB [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e], undoubtedly leading to high DALYs. Diabetes can increase susceptibility to tuberculosis, lead to poorer treatment outcomes, and complicate its management [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Elevated fasting plasma glucose has been shown to contribute to the global TB burden [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e], including the development of drug resistance [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Countries with low-middle and low SDI had higher diabetes-related DALYs because three-quarters of diabetes patients live in low- and middle-income countries [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eTobacco smoking is a proven independent risk factor for TB and significantly impacts many aspects of the disease, including development, treatment outcomes, and mortality[\u003cspan additionalcitationids=\"CR41\" citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. While tobacco use presents an avoidable threat to public health worldwide, the global prevalence among people aged 15 years and older decreased from 32.7% in 2000 to 21.7% in 2020[\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e], consistent with the trend in TB-related DALYs. Notably, diabetes-related DALYs were strongly linked to tobacco use[\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAdditionally, our findings showed that alcohol use contributed to TB DALYs among older people. Alcohol is the leading risk factor for premature mortality and disability among those aged 20 to 39 years, accounting for 13% of all deaths in this age group. In contrast, individuals aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years had lower percentages (\u0026lt;\u0026thinsp;5%) of alcohol-attributable deaths [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. Alcohol use disorders increased TB risk due to alcohol-related social mixing patterns and the influence of alcohol and alcohol-related conditions on the immune system [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. Therefore, we recommend minimizing or eliminating smoking and alcohol consumption. Studies have shown that controlling smoking and alcohol consumption can reduce tuberculosis deaths in the elderly [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. Although total alcohol consumption per capita globally decreased slightly from 5.7 liters in 2010 to 5.5 liters in 2019 (a 4.5% relative reduction) [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e], alcohol-related DALYs decreased globally and across SDI levels. Our findings highlight the importance of providing better care and access to case-detection, intervention, and clinical management for TB, diabetes, tobacco use, and alcohol use systematically. Studies have shown that, for older people, controlling smoking and alcohol consumption can help reduce tuberculosis deaths [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\u003ch2\u003eStrengths and limitations of this study\u003c/h2\u003e\u003cp\u003eThis study has several strengths and novel aspects. First, aligning TB control with health economics by focusing on the elderly population elucidates specific disease burden characteristics and influencing factors within this demographic, providing a foundation for policy preferences and strategic development. Second, the DALY metric, which integrates YLLs and YLDs, offers a comprehensive measure of the disease's impact on the population. Third, the GBD study furnishes global, regional, and country-specific data, facilitating cross-regional comparisons and enhancing the understanding of the geographic distribution and temporal trends in TB burden. Finally, analyzing data from 1990 to 2021 allows for the observation of TB burden trends over time, aiding in the assessment of control strategy effectiveness and the adjustment of future policies.\u003c/p\u003e\u003cp\u003eDespite leveraging a comprehensive global dataset with detailed country-level and regional data, this study has several limitations. First, data completeness and quality from certain countries or regions may be suboptimal, potentially affecting the accuracy and reliability of the analysis. The inherent variability in data quality across countries and years often necessitates using estimates, leading to wider confidence intervals and increased uncertainty in the absence of robust data. Second, GBD studies predominantly provide descriptive analyses, limiting the ability to infer causality. To gain a deeper understanding of the factors influencing the TB burden, it is crucial to combine these findings with other research methodologies. Third, the database encompasses a limited range of influencing factors, potentially overlooking contributions from other critical determinants, such as malnutrition. Future research should incorporate findings from previous studies to address these additional factors and provide a more comprehensive analysis.\u003c/p\u003e\u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe tuberculosis burden among older adults has significantly increased, with disparities observed across countries with varying sociodemographic indices, accounting for nearly one-fifth of the global TB burden by 2021. These findings offer crucial insights for policy development by the WHO and global health leaders.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eTB Tuberculosis\u003c/p\u003e\u003cp\u003eDALY Disability adjusted life years\u003c/p\u003e\u003cp\u003eYLL Years of life lost\u003c/p\u003e\u003cp\u003eYLD Years lived with disability\u003c/p\u003e\u003cp\u003eAAPC Average annual percentage changes\u003c/p\u003e\u003cp\u003eGBD Global Burden of Disease\u003c/p\u003e\u003cp\u003eUI Uncertainty intervals\u003c/p\u003e\u003cp\u003eCI Confidence intervals\u003c/p\u003e\u003cp\u003eASR Age-standardized rates\u003c/p\u003e\u003cp\u003eSDI Socio-Demographic Index\u003c/p\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate\u003c/strong\u003e\u003cp\u003eThe protocol of the GBD 2021 has been approved by the research ethics board at the University of Washington. The GBD 2021 shall be conducted in full compliance with University of Washington policies and procedures, as well as applicable federal, state, and local laws.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003cp\u003eNot applicable.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e\u003cp\u003eThis work was supported by the National Science and Technology Major Project of China (grant 2017ZX10201302-001) and the Tuberculosis Control and Prevention Programme of China CDC. The funder of the study had no role in the study design, data collection, data analysis, data interpretation, or the writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eYS Liu: first draft writing, review, editing, conceptualization, methodology, data acquisition; CY Z and T L: data acquisition, figures, review and editing; MK F, YH L, H C, J C: review and editing; H Z and ZG G: conceptualization, review, editing, methodology and supervision.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e\u003cp\u003eThe authors appreciate the works by the GBD Study 2021 collaborators.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets analysed during the current study are available at https://vizhub.healthdata.org/gbd-results/.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGlobal tuberculosis report 2023. Licence: CC by-NC-SA 3.0 IGO. 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Global, regional, and national mortality of tuberculosis attributable to alcohol and tobacco from 1990 to 2019: a modelling study based on the Global Burden of Disease study 2019. J Glob Health. 2024. 2024;14:4023. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve\u0026amp;db=pubmed\u0026amp;dopt=Abstract\u0026amp;list_uids=38175959\u0026amp;query_hl=1\u003c/span\u003e\u003cspan address=\"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve\u0026amp;db=pubmed\u0026amp;dopt=Abstract\u0026amp;list_uids=38175959\u0026amp;query_hl=1\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.7189/jogh.14.04023\u003c/span\u003e\u003cspan address=\"10.7189/jogh.14.04023\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7602192/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7602192/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eTo estimate the burden, trends, and inequalities of tuberculosis (TB) among older adults at the global, regional, and national levels from 1990 to 2021.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eWe analyzed the global burden of tuberculosis in adults aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years using data from the GBD Study 2021 across 204 countries from 1990 to 2021. Disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) were assessed, with uncertainty quantified by 95% \u003cem\u003eCIs\u003c/em\u003e. Countries were grouped by region and sociodemographic index (SDI). Descriptive statistics, age-standardized rates (ASRs), and average annual percentage changes (AAPCs) were computed to evaluate TB burden variations by age, sex, and location. Changes in factors affecting DALYs for tuberculosis in older adults were also analyzed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eBetween 1990 and 2021, the proportion of tuberculosis-related DALYs among older adults increased from 12.45% to 18.38% of the total population. In 2021, an estimated 8.63\u0026nbsp;million individuals aged 65 years and older (95% \u003cem\u003eUI\u003c/em\u003e 7.75 to 9.74) were affected by TB-related DALYs, with an age-standardized rate of 1,122 per 100,000 population. Although the age-standardized DALY rate for older adults steadily declined from 1990 to 2021, the annual reduction was slower than that of the overall population (-3.26% per year [95% \u003cem\u003eUI\u003c/em\u003e -3.38% to -3.15%]). While YLLs decreased, the proportion of YLDs rose from 6.5% to 10.2% of total DALYs during the same period. Men consistently showed higher DALY counts and rates than women across all age groups in 2021. Globally, TB-related DALYs decreased across sociodemographic strata, with the largest declines in high SDI countries (-4.98% [95% \u003cem\u003eUI\u003c/em\u003e -5.19% to -4.78%]) and the slowest in low SDI countries (-2.73% [95% \u003cem\u003eUI\u003c/em\u003e -2.85% to -2.62%]). In 2021, Central and Eastern Sub-Saharan Africa (9,899 and 8,439 per 100,000, respectively) had the highest DALY rates, whereas high-income regions had the lowest. High fasting plasma glucose, tobacco use, and alcohol consumption were key contributors to TB DALYs, with only fasting plasma glucose rising between 1990 and 2021.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThe tuberculosis burden among older adults has significantly increased, with disparities observed across countries with varying sociodemographic indices, accounting for nearly one-fifth of the global TB burden by 2021. Managing high fasting plasma glucose levels remains a major challenge for older adults. Targeted guidelines are urgently needed to address these specific health needs.\u003c/p\u003e","manuscriptTitle":"Global Burden of Tuberculosis in Adults Aged 65 Years and Older, 1990–2021: A Population-Based Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-30 10:40:58","doi":"10.21203/rs.3.rs-7602192/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"379235fa-fb0f-4a2b-8114-a597ac061a82","owner":[],"postedDate":"October 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-14T16:08:32+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-30 10:40:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7602192","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7602192","identity":"rs-7602192","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}