well as new tools to support prevention, care and implementation, including digital health technologies [4, 5]. Although there have been considerable challenges and shortcomings in the available funding for TB research and development (US$915 million in 2020, less than half of the intended target set by the international community) [6], the last decade has witnessed unprecedented efforts in the development of novel diagnostics, promising vaccine candidates, and medicines. In the field of prevention, several milestones have been achieved. The development and roll out of short and ultra-short regimens for TB prevention, including weekly high-dose rifapentine and isoniazid for 3 months [6] and 1 month of daily rifapentine plus isoniazid to prevent HIV-related TB [7] have represented relevant advances, which have quickly translated into national and international policies [8]. In addition, several TB drug preventive trials for both drug-susceptible (DS)-TB and DR-TB are currently in progress, with the hope of increasing the preventive efficacy, improving safety in vulnerable populations, such as children or PLHIV, or further shortening the duration of these regimens [9]. Similarly, the field of TB vaccine development is experiencing a period of unprecedented optimism, mostly based on the promising results of two recent efficacy studies into prevention of disease and infection [10, 11]. The protein-subunit vaccine candidate M72/AS01E has shown an efficacy of ∼50% against progression from infection to disease in a large phase 2B study conducted in Kenya, South Africa and Zambia [10]. A large phase 3 registration trial is now in preparation and is expected to start enrolment during 2024. In addition, a study in South African adolescents has shown that BCG revaccination provides ∼45% protection against sustained IGRA conversion [11]. These findings are currently being followed-up with a further trial whose results are also expected in 2024. There has never been a time in history with more TB vaccine candidates being tested in large phase 3 trials (currently four at phase 3 and 17 in clinical development) [12]. Novel successful platforms used in the development of COVID-19 vaccines (using mRNA for TB antigen delivery) are already being tested in humans for TB [13]. We might be very close to adding a game-changing element to our tool kit in fight against TB. The quest for improved point-of-care diagnostics continues to be a priority for TB research [5]. Importantly, novel, rapid molecular assays have been developed and recommended by the WHO for different levels of care [14]. Promising research is being conducted to develop sputum-free TB diagnostics, which are especially relevant for populations in whom TB laboratory confirmation continues to be suboptimal, such as children, PLHIV or in cases of EPTB [15]. Unfortunately, the only true point-of-care non-sputum-based TB diagnostic test continues to be TB-LAM, which is recommended for PLHIV under specific criteria [16]. Disappointingly, its uptake is low despite having evidence of its positive impact in reducing TB mortality [17, 18]. Thus, the quest for novel point-of-care tests that can accelerate TB diagnosis at decentralised levels of care remains. Although the WHO recently included novel tools as part of the new TB-screening recommendations, such as C-reactive protein or artificial intelligence-based computer-aided detection to analyse digital CXR, there is a need for more specific assays for both screening or triage. New diagnostics capable of identifying individuals that are at high risk of TB progression are a priority target product profile in the field of TB diagnostics [19]. Despite decades of limited progress in global efforts to establish shorter treatment regimens for DS-TB (including several unsuccessful phase 3 treatment-shortening trials) [20–22], the field has been invigorated by exciting results demonstrating the effectiveness of a 4-month regimen against xiv https://doi.org/10.1183/2312508X.10025822
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