Tuberculosis conundrum - current and future scenarios: A proposed comprehensive approach combining laboratory, imaging, and computing advances.

Tuberculosis (TB) remains a global threat, with the rise of multiple and extensively drug resistant TB posing additional challenges. The International health community has set various 5-yearly targets for TB elimination: mathematical modelling suggests that a 2050 target is feasible with a strategy combining better diagnostics, drugs, and vaccines to detect and treat both latent and active infection. The availability of rapid and highly sensitive diagnostic tools (Gene-Xpert, TB-Quick) will vastly facilitate population-level identification of TB (including rifampicin resistance and through it, multi-drug-resistant TB). Basic-research advances have illuminated molecular mechanisms in TB, including the protective role of Vitamin D. Also, Mycobacterium tuberculosis impairs the host immune response through epigenetic mechanisms (histone-binding modulation). Imaging will continue to be key, both for initial diagnosis and follow-up. We discuss advances in multiple imaging modalities to evaluate TB tissue changes, such as molecular imaging techniques (including pathogen-specific positron emission tomography imaging agents), non-invasive temporal monitoring, and computing enhancements to improve data acquisition and reduce scan times. Big data analysis and Artificial Intelligence (AI) algorithms, notably in the AI sub-field called "Deep Learning", can potentially increase the speed and accuracy of diagnosis. Additionally, Federated learning makes multi-institutional/multi-city AI-based collaborations possible without sharing identifiable patient data. More powerful hardware designs - , Edge and Quantum Computing- will facilitate the role of computing applications in TB. However, "Artificial Intelligence needs real Intelligence to guide it!" To have maximal impact, AI must use a holistic approach that incorporates time tested human wisdom gained over decades from the full gamut of TB, , key imaging and clinical parameters, including prognostic indicators, plus bacterial and epidemiologic data. We propose a similar holistic approach at the level of national/international policy formulation and implementation, to enable effective culmination of TB's endgame, summarizing it with the acronym "TB - REVISITED".