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Competing Interests: We declare no competing interests.

Background: An estimated one fourth of the world's population is infected with Mycobacterium tuberculosis, and 5-10% of those infected develop tuberculosis in their lifetime. Preventing tuberculosis is one of the most underutilized but essential components of curtailing the tuberculosis epidemic. Moreover, current evidence illustrates that tuberculosis manifestations occur along a dynamic spectrum from infection to disease rather than a binary state as historically conceptualized. Elucidating determinants of transition between these states is crucial to decreasing the tuberculosis burden and reaching the END-TB Strategy goals as defined by the WHO. Vaccination, detection of infection, and provision of preventive treatment are key elements of tuberculosis prevention., Objectives: This review provides a comprehensive summary of recent evidence and state-of-the-art updates on advancements to prevent tuberculosis in various settings and high-risk populations., Sources: We identified relevant studies in the literature and synthesized the findings to provide an overview of the current state of tuberculosis prevention strategies and latest research developments., Content: We present the current knowledge and recommendations regarding tuberculosis prevention, with a focus on M. bovis Bacille-Calmette-Guérin vaccination and novel vaccine candidates, tests for latent infection with M. tuberculosis, regimens available for tuberculosis preventive treatment and recommendations in low- and high-burden settings., Implications: Effective tuberculosis prevention worldwide requires a multipronged approach that addresses social determinants, and improves access to tuberculosis detection and to new short tuberculosis preventive treatment regimens. Robust collaboration and innovative research are needed to reduce the global burden of tuberculosis and develop new detection tools, vaccines, and preventive treatments that serve all populations and ages., (Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Approximately 10·6 million people worldwide develop tuberculosis each year, representing a failure in epidemic control that is accentuated by the absence of effective vaccines to prevent infection or disease in adolescents and adults. Without effective vaccines, tuberculosis prevention has relied on testing for Mycobacterium tuberculosis infection and treating with antibiotics to prevent progression to tuberculosis disease, known as tuberculosis preventive treatment (TPT). Novel tuberculosis vaccines are in development and phase 3 efficacy trials are imminent. The development of effective, shorter, and safer TPT regimens has broadened the groups eligible for TPT beyond people with HIV and child contacts of people with tuberculosis; future vaccine trials will be undertaken in an era of increased TPT access. Changes in the prevention standard will have implications for tuberculosis vaccine trials of disease prevention, for which safety and sufficient accrual of cases are crucial. In this paper, we examine the urgent need for trials that allow the evaluation of new vaccines and fulfil the ethical duty of researchers to provide TPT. We observe how HIV vaccine trials have incorporated preventive treatment in the form of pre-exposure prophylaxis, propose trial designs that integrate TPT, and summarise considerations for each design in terms of trial validity, efficiency, participant safety, and ethics., Competing Interests: Declaration of interests GC reports research funding from the US National Institutes of Health (NIH)/Division of AIDS (UM1AI068614, UM1AI068636, 5UM1AI154463). Since March, 2022, MQ has worked full time as an employee of Evidera, a commercial research organisation that receives funding to conduct research on behalf of private pharmaceutical companies; this research is unrelated to the topic of this Personal View. RGW acknowledges project funding from the Wellcome Trust (218261/Z/19/Z), NIH (1R01AI147321-01), European and Developing Countries Clinical Trials Partnership (RIA208D-2505B), UK Medical Research Council (CCF17-7779 via SET Bloomsbury), UK Economic and Social Research Council (ES/P008011/1), Bill & Melinda Gates Foundation (OPP1084276, OPP1135288 & INV-001754), and WHO (2020/985800-0). All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Competing Interests: MXR is the recipient of a Wellcome Trust Investigator Award on tuberculosis and diabetes. IA is the recipient of an EU funded award to End-VOC (End SARS-CoV-2 variants of concern). The authors declare no other competing interests.