Tuberculosis (TB) remains one of the world's greatest threats.1 The World Health Organization's Global Tuberculosis Report 2023 estimated that there were 10.6million new cases of TB globally in 2022, with an incidence of 133 per 100,000, and a 3.9% increase of incidence between 2020 and 2022.2 Furthermore, epidemics of novel coronavirus infections have a much greater impact on TB mortality than HIV/AIDS.3

Looking back at the history of global targets for TB, in 1991, the World Health Assembly set a global target for the year 2000: a model-based setting to reduce prevalence and incidence by 5–10% per year.4 This phase of the strategy, known as DOTS (Directly-Observed Treatment Strategy), centered on providing free treatment for sputum-smear-positive TB patients and using an intensive period of supervised management of the treatment after an initial positive smear.5 Subsequently, in 2006 WHO proposed the Stop TB strategy, which aimed to reduce the prevalence of TB and the mortality rate of TB by half from the 1990 level by 2015.6,7 This strategy significantly expanded the scope of TB prevention and control, not only targeting highly contagious TB, but also strengthening the rigorous management and prevention of non-contagious TB.8,9 Also in 2014, the 67th World Health Assembly endorsed the WHO END TB strategy and the Sustainable Development Goals (SDGs), which is a strategy for eliminating TB, with a focus on the prevention and the treatment of TB.10,11 The common aim was to reduce TB deaths by 95% between 2015 and 2035, reduce new TB cases by 90%, and the annual reduction should be at least 7%.12–14 The scope of prevention and control of this stage extends beyond pulmonary TB to include extra pulmonary TB, close contacts of TB, and latent infections in high-risk groups, achieving broader coverage.15,16

Although WHO regularly releases global TB reports, so far, limited study based on GBD data analyzed and evaluated TB prevention and control strategies with its risk factors at different stages, the possible influencing factors at different stages. Analyzing the evaluation of the effectiveness of TB prevention and control in different stages and summarizing the experience has theoretical and practical significance for the optimization of future actions. Therefore, we conducted this study.

Our results show that from 1990 to 2021, the best TB controlled indicator is ASDR, followed by ASIR and finally ASPR.2 Moreover, control of TB prevalence deserves attention. In terms of phase effects, it is evident that phase II control results in the best results in terms of morbidity, disease and mortality control. Notably, stage 1 had better control than stage 3 in terms of morbidity and illness, while control of mortality was lower than in stage 3.

Looking at the results for the less well controlled ASPR, it is observed that the largest annual increase in Stage I was in Taiwan, China, while the largest annual decrease was in Spain. In contrast, in Stage 2, the largest annual increase was in Sri Lanka (which also had the second largest increase in Stage 1) and the largest annual decrease was in Cape Verde. Furthermore, in stage 3, the largest annual increase was in the United States and the largest annual decrease was in Côte d’Ivoire.

In order to explore the reasons for the increase or decrease in prevalence, we took these typical countries as examples and went to search the literature on TB prevention and control in these countries at the corresponding stages and found some possible explanations. In Taiwan, a review in 200619 showed that the increasing burden of multidrug-resistant TB infections, high mortality rates, the lack of a nationwide surveillance system to determine drug resistance trends and status, and the inadequacy of the current TB control infrastructure and training to accomplish the tasks required to implement the Directly Observed Treatment Shortcourse (DOTS) strategy have had a significant impact on public health in Taiwan. In contrast, a study conducted by the TIR team of the Spanish National Institute of Public Health (INSP)20 between June 1999 and May 2000 showed that 82% of the 1515 cases treated had a satisfactory outcome. Furthermore, the incidence of tuberculosis showed an improving trend in recent years, following a rise linked to AIDS.

A study in Sri Lanka in 200821 showed that both male and female TB patients in Sri Lanka were severely malnourished. As a result, patients are advised to receive nutritional support during treatment, and there is a pressing need to study the exact nutritional deficiencies at the micronutrient level and their impact on the immune system. Meanwhile, a 2008 study on TB uptake in Cape Verde22 showed an overall underreporting rate of 40% for TB in Praia, Cape Verde between 2006 and 2012.

Previous studies showed that in the United States,23–25 more than 80% of tuberculosis (TB) cases were estimated to be due to reactivation of latent tuberculosis infection (LTBI) acquired two years ago (“reactivated TB”). This may be one of the reasons for the rebound of TB in the United States. In recent years, several multicenter RCTs of genetic diagnostic techniques,26–29 retroviral therapy for TB have been conducted in African countries, including clinical trials for drug-resistant TB, patients with HIV, TB co-infection and a project to decentralize TB diagnosis in children. It is likely that the dissemination of research on these diagnostic and treatment technologies, as well as the implementation of favorable policy programs, have contributed to the control of TB ASPR in Côte d’Ivoire.30 However, the possibility of TB underreporting in Côte d’Ivoire cannot be ruled out.

Some studies31,32 reported that malnutrition, forced displacement and homelessness worse from 2015 to 2021. Global malnutrition rates have risen from 8.4% to 9.8%, with 22.7 million new people affected each year. As of 2022, 735million people globally are affected by malnutrition. This may be an influencing factor in the fact that the effects of the third phase are not as effective as those of the second phase. Regionally, Africa (21.9%) and Asia (10.6%) have the highest rates, while Western Europe and North America have rates below the global average: 3.4% and 2.5%, respectively.

These changes, consistent with our analysis of influencing factors, show that the SDI index is negatively correlated with TB control. However, the correlation between SDI and ASPR is not significant in East and Southeast Asia. Meanwhile, the TB ASPR in the middle and high SDI regions rebounded and increased in the third stage from a decline in the first two stages. Decomposition analysis showed that ASPR in middle and high SDI areas changed from demographic factors in the first stage, to epidemiologic factors in the second stage, to population aging factors in the third stage. It suggests that probably the middle and high SDI regions, due to the existence of changes in the countries included, the changes in risk factors have led to the reversal of TB prevention and control.

China has achieved a reduction in morbidity and mortality above the global average in the primary stage of END TB, in order to advance the END TB goal. We would like to share China's implementation strategies.33–35 Firstly, there is government guidance and monitoring, promotion of laws, regulations, and service systems, socioeconomic development, and improvement of population nutrition. In collaboration with the CDC, we will promote TB prevention and control in chronic disease prevention and treatment, infectious disease prevention and treatment, and community health education.36 Secondly, we will establish a strong alliance with the community to promote universal medical checkups and medical checkups for the elderly in conjunction with healthcare reform. At the same time, we will promote the integration of health care and prevention and the construction of medical communities to play a role in the prevention and control of tuberculosis.37 Thirdly, protecting and promoting human rights and equity, and continuing to promote BCG vaccination and preventive treatment for high-risk groups.38 Fourthly, under the premise of global cooperation, establish strategies and targets, improve the monitoring mechanism, combine passive and active monitoring, and realize the whole process of treatment management, making full use of the Internet and AI technology.39

As ASIR and ASDR have achieved good control rate results in the three different phases, especially in the second phase, which has accomplished the target. Although the third phase still requires further efforts to complete the END TB target, it is also necessary to acknowledge the significant achievements in TB morbidity and mortality control globally.

According to the WHO Global tuberculosis report 2024, the rise in the number of incidence cases of TB globally that began during the 2019 coronavirus disease pandemic had slowed and began to stabilize, meanwhile, the number of global TB deaths declined in 2023, consolidating the decline seen in 2022. The decline in the number of TB deaths and the slowdown in the growth of TB incidence since 2022 were the result of a substantial recovery in TB diagnosis and treatment post-COVID.40 This is consistent with the results of the 2016–2021 phase of our study, in which ASIR and ASDR were relatively well controlled, but control of ASPR needed to be further strengthened.

Based on our study, we would like to make the following recommendations: first, for countries with medium-high or higher SDI, the control of ASIR and ASDR requires more attention and more resources to prevent the emergence of new-onset TB patients and to reduce the mortality of TB patients. Second, for countries with medium-high or higher SDI, more attention must be paid to the risks associated with population aging, and more methods are needed to reduce the impact of aging on TB. Third, among the lifestyle factors, continuing to strengthen the promotion of smoking, alcohol consumption, and physical activity is of great significance for the prevention and control of TB. It is also important to reduce the percentage of high BMI population, especially in countries prone to obesity such as medium and high SDI, which may be an important way to accelerate the realization of END TB goals. Finally, in the post-COVID era, more research on prevention and control strategy, disease burden trend, diagnosis, treatment, and rehabilitation is needed to help achieve the END TB goal.

There are several strengths in this research. Firstly, the practical significance is an important feature in this research, which can better guide for the next step TB control and prevention. Secondly, the data included is a large scale, long-term and authoritative database. Thirdly, the methods in this research are powerful, especially in risk factors analysis like SDI correlation plot and decomposition analysis. However, this study had several limitations. Firstly, GBD data were global estimates, and this study was an ecological study based on estimated data. Secondly, our analysis of the relationship between disease burden indicators and SDI could not explain causality. Lastly, the exploration of risk factors was limited by the currently limited data, which might overlook some factors. In the further study, we could explore some more technical interventions and policy suggestions for controlling and prevention in END TB stage, especially in high TB burden countries.

In conclusion, the control of TB morbidity and mortality has been a great achievement in all the three different phases of the TB control strategy, and a concerted global effort is still needed in phase 3 to reach the END TB. However, TB prevalence control needs to be emphasized, especially in the middle and high SDI areas. More good prevention and control strategies are needed to collectively push the world to achieve the END TB goal in 2035.

Since this research is based on global burden of disease study 2021 database. This study is approved by the ethics committee of University of Washington from Institute for Health Metrics and Evaluation.

Hubei Provincial Public Health Leading Talent Project (no award/grant number); Young Talent Development Program of Wuhan Fourth Hospital (no award/grant number); Scientific Research Fund of Wuhan Municipal Health Commission (WG21Z10).

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

To download the data used in these analyses, please visit the Global Burden of Disease Results Tool (http://ghdx.healthdata.org/gbd-results-tool) and World Bank (https://data.worldbank.org/), made public by the Institute for Health Metrics and Evaluation.