Latent tuberculosis infection (LTBI) is a dynamic immune system balance that maintains a persistent immune response to the antigenic stimulus of Mycobacterium tuberculosis (MTB) after infection. Change to LTBI is not associated with signs, symptoms, imaging findings, or bacteriological evidence of active tuberculosis (TB) (1). The present evidence suggests that LTBI is not contagious. MTB was not eliminated and was in a state of suppression. If the immune system is weakened, dormant MTB may break through immunosuppression, proliferate, and spread throughout the body, which may progress to active TB (2). One-quarter of the global population is estimated to have LTBI, representing a significant reservoir of infection at risk of progression to active TB (1). The numerous patients with LTBI are a potential “patient pool” that continues to deliver new patients with active TB. Approximately 5–15% of people with LTBI would progress to active TB in their future lifetime, with the majority occurring within 2 years of infection (3). The risk of developing active TB may be higher if accompanied by other conditions, such as human immunodeficiency virus (HIV) infection or diabetes (4, 5).

The main goal of preventive treatment is to eliminate MTB present in a resting state in people with LTBI and reduce the possibility of reactivation at a later stage. All individuals who test positive for TB should be examined for signs, symptoms, and bacteriological or imaging results to assess the presence of active pulmonary or extrapulmonary TB before initiating preventive treatment. Preventive treatment is provided after TB has been definitively ruled out. Assuming no ongoing transmission from 2015 onwards, 961 million individuals will be infected by 2035. With a remote LTBI activation rate of 0.15% per year, the incidence of TB in these latent pools in 2035 would be 16.5/100,000 per year, which is higher than the target of the End TB Strategy for 2035 (6). In the absence of other interventions, the incidence of TB could approach 10/100,000 by 2035 if people with LTBI are administered preventive treatment or vaccinated with a new post-infection vaccine. If the treatment of active TB could be combined with the implementation of these interventions, the incidence of TB could be estimated to decrease from 110/100,000 in 2010 (close to the global average in 2010) to 1/100,000 by 2035 (7).

The World Health Organization recommends preventive treatment for people living with HIV, household contacts of patients with bacteriologically confirmed TB, and clinical risk groups. Treatment options include weekly isoniazid and rifapentine for 3 months, daily isoniazid and rifampicin for 3 months, daily isoniazid and rifapentine for 1 month, daily rifampicin for 4 months, and daily isoniazid for ≥6 months (8). Several countries have already reduced the incidence of TB by implementing preventive treatment for people with LTBI (9, 10). In 2018, the United Nations high-level meeting proposed that the number of people on TB preventive treatment should reach at least 30 million globally in 2018–2022; however, only 15.5 million people were provided with preventive treatment, equivalent to 52% of the target (11). A meta-analysis by Rustage et al. showed that the true proportion of preventive treatment initiation among migrants globally was estimated at 69%, and the true proportion of treatment completion was estimated at 74% (12). Bastos et al. observed that 60.4 and 41.9% of people living with HIV initiated and completed preventive treatment, respectively (13). Additionally, the proportion of initiation and completion of treatment among healthcare workers was only 38.5 and 32.0% (14). Considerable challenges and obstacles to the implementation of preventive treatments for LTBI are observed worldwide.

The importance of preventive treatment for LTBI has been widely recognized. However, its implementation effectiveness worldwide falls far short of the expected targets. Although previous studies have identified some barriers, there has been a lack of comprehensive synthesis of challenges from the perspectives of both the demand side (patients) and the supply side (healthcare workers, service systems, and policy support), as well as across the sequential stages of initiation and implementation. In this article, we systematically reviewed publications on the implementation of preventive treatments and explored the difficulties and challenges that may affect the initiation and implementation of preventive treatment from demand-side and supply-side perspectives. This could provide a scientific basis for promoting and enhancing the implementation of TB prevention and control strategies in the later stages.

We systematically searched PubMed and Embase databases using Boolean operators (Supplementary table S1). Peer-reviewed English-language articles published between January 1, 2010, and August 31, 2024, including quantitative and qualitative studies related to barriers to or promotion of preventive treatment, were included in the study.

This study conducted the literature screening process in accordance with the PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) (Figure 1). The exclusion criteria for literature screening were as follows: (1) Non-English publications; (2) Non-original research (e.g., conference abstracts, reviews); (3) Literature not directly related to the initiation or implementation barriers of preventive treatment for LTBI. The systematic literature search for this study was fully completed in September 2024, followed by systematic literature screening and data extraction conducted from September to October. And the manuscript was drafted and revised between November 2024 and January 2025. Relevant information on publications that met the criteria was extracted, including the first author, year of publication, study period, study area, study population, study type, proportion of treatment initiation, proportion of treatment completion, and barriers to the initiation and completion of preventive treatment (Supplementary table S2).

We used content analysis to systematically analyze the data from the included articles. Based on the time sequence of TB preventive treatment, the descriptions of potential barriers extracted from the included literature were categorized into two important phases: the initiation phase (encompassing detection and diagnosis) and the implementation phase (encompassing treatment and support). Meanwhile, conduct an in-depth analysis from both the demand-side and supply-side perspectives. For example, patients’ lack of knowledge about preventive treatment and concerns about adverse effects were categorized as barriers in the demand-side initiation phase. The healthcare workers’ lack of knowledge and insufficient resources were categorized as barriers at the supply-side initiation phase. In this way, we comprehensively and systematically identified the potential barriers existing at different stages and levels in preventive treatment. To present the research findings more intuitively, we used a conceptual model to display the analysis results, making the complex research findings clear at a glance and facilitating the readers’ understanding and grasp of key information.

Our study summarized the difficulties and challenges faced during the initiation and implementation of preventive treatment from the demand- and supply-side dimensions and integrated these findings into a conceptual model (Figure 2).

This review systematically summarized the multifaceted challenges associated with preventive treatment for LTBI documented between 2010 and 2024. The conceptual model constructed views challenges as the outcome of multi-level interacting factors. It advanced existing understanding by clarifying the interplay between patient perceptions, healthcare provider capabilities, and the infrastructure of the healthcare system throughout the treatment process. This provides a more nuanced theoretical basis for developing targeted, multidimensional interventions.

Acceptance of preventive treatment may be limited by insufficient knowledge of LTBI. The treatment attitude of the provider may also somewhat guide individuals. Improving correct awareness and acceptance of preventive treatment in the population are critical steps in implementing preventive treatment. Acceptance of preventive treatment increases when individuals believe that they can transmit MTB or have a better understanding of TB (20, 60, 61). Education on TB and LTBI can be integrated into the overall planning for teaching and health prevention. Public attention to TB and LTBI can be attracted by conducting various forms of popularization activities using multiple social media platforms. Simultaneously, social stigma may be reduced by combining regular LTBI testing with other programs (62).

Increasing the level of awareness of LTBI and understanding the benefits of preventive treatment among healthcare workers were the major contributing factors that enabled them to recommend treatment (63). When confronted with disease counseling, healthcare workers can encourage individuals to accept preventive treatment by adequately explaining it. Furthermore, the clinical professional skills training of healthcare workers should be strengthened to ensure that they have good handling abilities when dealing with adverse effects. Besides, short-course treatment regimens had a higher rate of treatment completion (58, 64). Therefore, short-course treatment regimens should be prioritized for the development of drug regimens. The development of new drugs or vaccines can reduce the risk of active TB and reduce the risk of adverse drug effects.

Enhanced adherence management is an important tool in completing preventive treatment. Implementation of LTBI screening in any setting or population should be followed by intensive adherence management, including further exclusion of TB diagnoses, implementation of preventive treatment, monitoring of adverse effects, and the occurrence of active TB. Considering that individuals have different levels of acceptance of preventive treatments, different management approaches should be adopted. For example, those who accept preventive treatment should focus on medication management to increase the rate of treatment completion. Those who do not accept treatment should strengthen health education and closely observe changes in infection or morbidity status. Patients who maintained their scheduled appointments were 10 times more likely to complete preventive treatment than those who missed one or more appointments (65). Therefore, providing appointment reminder services can somewhat help individuals complete their treatment (43). Adopting dynamic management methods such as regular home follow-up visits and video directly observed therapy also helps to strengthen adherence management and improve the treatment completion rate (58, 66–68).

Increasing the attention of the government and improving the service guarantee system are required. Strengthening financial support is an important solution for LTBI management (34). Individuals can be offered medical benefit policies to encourage them to complete the evaluation and treatment, such as increasing the proportion of medical insurance reimbursements for the cost of chest radiography, incorporating LTBI testing programs into routine screening programs, and providing free drugs. The provision of health insurance was a potential means of changing individual treatment behavior and increasing treatment completion rates (43, 69). Guaranteeing access to healthcare services by increasing the number of primary healthcare facilities and providing convenient outpatient appointments (61). Additionally, developing and implementing incentive policies to motivate healthcare workers to perform treatments is needed. Human resource security should be strengthened through the training and introduction of specialized technical personnel and the recruitment of community members who are well-connected and trusted by the community to participate in management in a coordinated manner.

This study extensively collected journal evidence on the topic through a systematic search and discussed the challenges that may be faced at different stages of preventive treatment from demand- and supply-side perspectives. However, this review had some limitations. First, the results of the studies were not meta-analyzed because of the limitations of the study types. Second, our findings should be interpreted in the context of regional variations in the incidence of TB. In high-burden areas, preventive treatment may face greater prioritization pressures as healthcare resources are primarily directed toward controlling active TB. Low-burden areas may have greater capacity to integrate LTBI screening and treatment into routine services. This disparity underscores the necessity of context-appropriate strategies when implementing LTBI preventive treatment programs. Future research could focus on this regional heterogeneity for more in-depth and targeted studies. Third, our restrictions on the English literature and publication times may have missed some relevant studies. Additionally, the quality of the included studies may have differed. Low-quality studies may have affected our conclusions. Therefore, there is a need to expand the collection scope of study types to obtain a sufficient amount and diverse data. Focus on high-level studies to further explore the barriers and influencing factors in the implementation of preventive treatment. This can provide a more detailed and reliable reference for the development and improvement of preventive treatment management strategies and help to improve the overall level of TB prevention and control.

Our findings suggest that multiple factors hinder the implementation of preventive treatment. Developing multidimensional interventions to address the challenges faced in preventive treatment, including improving individual understanding and acceptance of preventive treatment, increasing the level of knowledge and ability of healthcare workers, strengthening the management of treatment follow-up, and improving the service system and policy safeguards for preventive treatment is required. This not only provides practical optimization strategies for clinical practice but also provides detailed references for policy formulation and improvement, which will help to further accelerate the process of eliminating TB.